Free Health and Medical Articles

Method of recollagenation

2008-01-14T08:18:00.000-08:00

Abstract

A surgical method for implanting cadaver collagen for the restoration of lesions caused by the loss of collagen. The skin is perforated and a pocket is created under the skin. Human cadaver collagen is then introduced into the pocket and the skin perforation is closed. Over the next several months, the cadaver collagen is replaced by endogenous collagen.

Patent number: 5397352
Filing date: Aug 27, 1993
Issue date: Mar 14, 1995
Inventor: Steven Burres
Primary Examiner: Rob Clarke

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What is claimed is:

1. A method of recollagenation comprising:

a. identifying a skin depression for elevation;

b. perforating the skin with a needle adjacent to the said skin depression;

c. creating a pocket underneath the skin surface over said skin depression by swiveling said needle through the dermis;

d. cutting at least one strip or chip of freeze dried banked human fascia lata to be placed in said pocket;

e. soaking said strip or chip of fascia lata in a supersaturated sugar solution;

f. inserting said strip or chip of fascia lata through said skin surface above said pocket; and

g. closing said skin perforation.

2. The method of claim 1 wherein said skin depression is a scar.

3. The method of claim 2 wherein said scar is an acne scar.

4. The method of claim 2 wherein said scar is a chicken pox scar.

5. The method of claim 1 wherein said skin depression is a wrinkle.

6. The method of claim 1 wherein said skin depression is a fatty depression commonly referred to as cellulite.

7. The method of claim 1 wherein said strip or chip of banked human fascia lata is cut to the same size of said pocket.

8. The method of claim 1 wherein said supersaturated sugar solution is a supersaturated glucose solution.

Treated tissue for implantation and methods of preparation

2008-01-14T08:14:00.000-08:00

Abstract

This disclosure includes a method for generating a functional hybrid bioprosthesis. Tissue formed naturally of interstitial collagens is treated to kill native cells and remove potentially immunologically active soluble molecules. Then it may be treated sequentially with extracellular matrix adhesion factor, extracellular matrix glycosaminoglycan, and growth factor appropriate to the cell type required to function within the matrix, and incubating the transplant tissue matrix with cells that are either allogeneic or autologous for the recipient thereby imparting to the matrix the characteristics of the cell type and tissue selected. Tissues with a variety of functional bioactivities can thus be formed in vitro prior to graft transplantation or implantation which will exhibit reduced or no stimulation of an immunological response in the recipient.

Patent number: 5632778
Filing date: Jun 5, 1995
Issue date: May 27, 1997
Inventor: Steven Goldstein
Assignee: Cryolife, Inc

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What is claimed is:

1. A process for generating a substantially non-immunogenic tissue matrix suitable for subsequent processing into an implant tissue comprising:

A. eliminating native cells by treating a tissue with components selected from the group consisting enzymes and nucleases effective to inhibit subsequent native cell growth in the treated tissue and effective to limit generation of new immunological sites in the tissue thus producing a tissue matrix;

B. treating the tissue matrix with cellular adhesion factor to promote subsequent attachment of cultured allogeneic or autologous cells to the surfaces of the tissue matrix; and

C. repopulating the tissue matrix throughout the matrix with cultured allogeneic or autologous cells.

2. The process of claim 1 wherein, during step A, the tissue is treated with a low ionic strength solution of nucleases effective to decellularize the tissue and provide a tissue matrix of limited immunogenicity.

3. The process of claim 2 wherein the low ionic strength solution of nucleases includes at least one member, selected from the group consisting of RNAase A, DNAase I, EcoR I and Hind III.

4. The process of claim 2 wherein the nucleases employed are ribonuclease A and deoxyribonuclease I.

5. The process of claim 1 further comprising cryopreserving the tissue matrix after step A and prior to further processing.

6. The process of claim 2 further comprising cyropreserving the tissue matrix after step A and prior to further processing.

7. The process of claim 5 further comprising sterilizing the tissue or tissue matrix or both.

8. The process of claim 1 wherein the process further comprises obtaining natural mammalian tissue, cryopreserving the tissue, removing the tissue from cryopreservation and then treating the tissue in accordance with claim 1.

9. The process of claim 8 wherein the tissue is of porcine heart valve origin.

10. The process of claim 9 wherein the heart valve is a pulmonary or an aortic heart valve.

11. The process of claim 1 wherein step A further comprises treatment with a hypotonic aqueous solution.

12. The process of claim 11 herein said hypotonic aqueous solution is a buffered aqueous solution effective to cause cell lysis.

13. The process of claim 12 wherein the tissue is porcine heart valve tissue.

14. The process of claim 13 wherein the heart valve is a pulmonary or an aortic heart valve.

15. The process of claim 14 further comprising the step of cryopreserving the porcine heart valve tissue matrix produced by step A.

Breast prosthesis with biologically absorbable outer container

2008-01-14T04:08:00.000-08:00

Abstract

A newly developed breast prosthesis overcomes the tightness and contracture of the fibrous capsule which forms around the existing prosthesis. The unique construction of the new prosthesis causes the capsule to form at a predetermined, controlled distance from the surface thereof. This prosthesis is constructed with a first phase or outer temporary component and a second phase or inner permanent component. The inner component is a container or sac of a flexible, non-absorbable material filled with a fluid or gel filler material. The temporary outer component is an outer container or cover of a material which is absorbable under the conditions of use, and an inert filler material, preferably an absorbable, biologically acceptable liquid, e.g. saline solution, filling the space between the inner and outer components. The inner component is preferably of silicone rubber film and is filled with a silicone gel. The outer portion is in the form of a sheet, film or coating of a material...

Patent number: 4298998
Filing date: Dec 8, 1980
Issue date: Nov 10, 1981
Inventor: Sadeque S. Naficy

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What is claimed is:

1. A breast prosthesis comprising an inner core of biologically compatible, non-absorbable material, and

biologically absorbable means surrounding said core for effecting capsule formation at a selected and controlled distance from said core without contractive pressure thereon after surgical implantation.

2. A breast prosthesis according to claim 1 in which

said means comprises a flexible wall covering or container surrounding said inner core,

said biologically absorbable flexible wall covering or container at least at the time of surgical implantation having a biologically compatible liquid in the space between said flexible wall covering or container and said core.

3. A breast prosthesis comprising

an inner coherent core of biologically compatible, non-absorbable material and

an outer covering of absorbable material having an outer surface spaced from the surface of said core.

4. A breast prosthesis according to claim 2 in which

said absorbable material is a material selected from the group consisting of materials which are absorbed by hydrolysis, materials which are absorbed by phagocytosis, materials which are absorbed by enzymatic decomposition and materials which are absorbed by chemical or biological reactions.

5. A breast prosthesis according to claim 3 in which

said absorbable material is a material which is formed in situ by reaction of an initially non-absorbable material with added chemicals or enzymes.

6. A breast prosthesis according to claim 5 in which

said chemicals or enzymes are added to said initially non-absorbable material at the time of manufacture.

7. A breast prosthesis according to claim 5 in which

said chemicals or enzymes are added to said initially non-absorbable material in admixture with fluid introduced inside said outer covering.

8. A breast prosthesis according to claim 7 in which

said chemicals or enzymes are added to said fluid after surgical implantation of said prosthesis.

9. A breast prosthesis according to claim 5 in which

said chemicals or enzymes are added to said initially non-absorbable material at the time of surgical implantation of said prosthesis.

10. A breast prosthesis according to claim 3 in which

said absorbable material is a material which is formed in situ by physical treatment of an initially non-absorbable material to render the same absorbable.

11. A breast prosthesis according to claim 3 in which

said outer covering of absorbable material comprises

an outer container of a flexible absorbable material spaced from said core, and

an inert filler material filling the space between said outer container and said core.

12. A breast prosthesis according to claim 11 in which

said outer container comprises a film of a natural or synthetic or semisynthetic absorbable material.

13. A breast prosthesis according to claim 11 in which

said outer container comprises a film of a material selected from the group consisting of catgut, chromic gut, reconstituted animal collagen, reconstituted vegetable protein, absorbable carbohydrate polymers, and absorbable synthetic or semisynthetic polymers.

14. A breast prosthesis according to claim 13 in which

said film is an absorbable polyester of a dibasic acid.

15. A breast prosthesis according to claim 14 in which

said film is an absorbable condensation polymer of a hydroxycarboxylic acid.

16. A breast prosthesis according to claim 15 in which

said polymer is polyglycolic acid or polyglactin 910.

17. A breast prosthesis according to claim 11 in which

said outer container comprises a film of an absorbable polymer of cellulose or amylose or derivatives thereof.

18. A breast prosthesis according to claim 11 in which

said inert filler material is a biologically compatible solution.

19. A breast prosthesis according to claim 11 in which

said inner core comprises an inner container of a biologically compatible non-absorbable film enclosing a quantity of fluid material.

20. A breast prosthesis according to claim 19 in which

said fluid material in said inner container is a biologically compatible liquid.

21. A breast prosthesis according to claim 19 in which

said fluid material in said inner container is a gel material.

22. A breast prosthesis according to claim 19 in which

said inner core comprises a container of silicone rubber film enclosing a quantity of silicone gel.

23. A breast prosthesis according to claim 11 in which

said inner core comprises a non-absorbable sponge of a biologically compatible material.

24. A breast prosthesis according to claim 11 in which

said inner core comprises a sponge enclosed in a biologically compatible, non-absorbable film.

25. A breast prosthesis according to claim 3 in which

said outer covering comprises an absorbable sponge.

26. A breast prosthesis according to claim 3 in which

said inner core comprises a double lumen prosthesis.

POST COSMETIC SURGERY PROTECTOR

2008-01-14T04:07:00.000-08:00

Patent number: 3804087
Filing date: Jul 24, 1972
Issue date: Apr 1974
Inventor: Caron Sarnoff

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Microsurgical technique for cosmetic surgery

2008-01-14T04:05:00.000-08:00

Abstract

A procedure for supporting the soft tissue of a patient's scalp in a superior position using a microanchor includes forming a plurality of incisions proximate to the soft tissue to be moved, inserting an endoscope through at least of one of the incisions and undermining the soft tissue to be moved while at least a portion of the undermining process is viewed through the endoscope. At least one microanchor having a generally cylindrical body including a first bone contacting end, a second trailing end and bone fixation means formed on at least a portion of an outer surface of the microanchor between the first and second ends is provided. Each of the one or more microanchors has a length of less than about 4.0 mm and has a predetermined length of suture thread attached thereto. At least one pilot hole is formed in the patient's cranium through the incisions made therein. The one or more microanchors are inserted into the one or more pilot holes, the soft tissue is moved to the...

Patent number: 5950633
Filing date: Oct 2, 1997
Issue date: Sep 14, 1999
Inventors: Richard J. Lynch, Tommy L. Turpin
Assignee: Ethicon, Inc.
Primary Examiner: Dinh X. Nguyen

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What is claimed is:

1. A surgical procedure for supporting soft tissue of a patient's scalp in a superior position using a suture anchor, comprising the steps of:

making a plurality of incisions proximate to the soft tissue to be moved;

inserting an endoscope through at least one of the incisions;

undermining the soft tissue to be moved while viewing at least a portion of the undermining process through the endoscope;

forming at least one pilot hole in the cranium through one of the incisions;

providing one or more microanchors having a generally cylindrical body including a first bone contacting end, a second trailing end and bone fixation means formed on at least a portion of an outer surface of the microanchor between the first and second ends, the one or more microanchors each having a length of less than about 4.0 mm and having a predetermined length of suture thread attached thereto;

inserting the one or more microanchors into the at least one pilot hole in the cranium;

moving the soft tissue to a desired superior position; and

suturing the soft tissue in the desired position.

2. The procedure of claim 1, wherein the bone fixation means comprise external threads with a major diameter of less than about 2.4 mm.

3. The procedure of claim 2, wherein the microanchor has a length of about 3.5 mm and a major diameter of about 2.0 mm.

4. The procedure of claim 2, wherein each microanchor is constructed from a metal.

5. The procedure of claim 1, wherein each microanchor is removably pre-mated to a suture anchor insertion tool.

6. The procedure of claim 1, wherein the bone fixation means comprises at least one deformable barb capable of penetrating bone tissue.

7. The procedure of claim 6, wherein the microanchor body is composed at least partially of titanium and the deformable barbs are constructed from a shape memory material.

8. The procedure of claim 7, wherein the bone fixation means comprises two opposed deformable barbs capable of penetrating bone tissue.

9. The procedure of claim 6, wherein the microanchor has a diameter of less than about 1.5 millimeters.

10. The procedure of claim 9, wherein the microanchor has a diameter of about 1.3 and a length of about 3.7 mm.

11. The procedure of claim 6, wherein each microanchor is removably pre-mated to a suture anchor insertion tool.

12. The procedure of claim 1, wherein the pilot holes are formed using a drill bit having an effective length of less than about 5 millimeters and having a scoring means suitable to provide clearance around the pilot hole to allow for a suture anchor insertion tool to insert the microanchor at or below the surface of the cranium.

13. The procedure of claim 1, wherein the plurality of incisions include parasagital incisions carried down to the periosteum, are located proximally to the hairline of the scalp and have a length between approximately 1.0 and 2.0 millimeters.

14. The procedure of claim 13, wherein a periosteal elevator is employed to undermine the tissue to be moved.

15. The procedure of claim 13, wherein pilot holes are drilled in a posterior portion of the incisions after manually placing the soft tissue in the desired position.

16. A surgical procedure for supporting soft tissue of a patient's scalp in a superior position using a suture anchor comprising:

making a plurality of incisions proximate to the hairline of the scalp;

undermining the soft tissue to be moved;

moving the soft tissue to a desired superior position;

providing at least one microanchor, pre-loaded with suture thread and removably pre-mated to a suture anchor insertion tool, the microanchor comprising a generally cylindrical body having external threads on at least a portion thereof, having a major diameter of less than about 3.0 millimeters;

forming a plurality of pilot holes in the scalp and corresponding cranium using a drill bit having an effective length of less than about 5 millimeters and having a scoring means suitable to provide clearance around the pilot hole to allow for a suture anchor insertion tool to insert the microanchor at or below the surface of the cranium;

inserting the microanchors into the pilot holes; and

suturing the soft tissue into the desired superior position.

Method of reducing lung size

2008-01-14T04:03:00.000-08:00

Abstract

A device, system, and method provides for lung size reduction by permanently collapsing at least a portion of a lung. The lung portion may be collapsed by obstructing the air passageway which communicates the lung portion to be collapsed. The air passageway may be obstructed by an obstructing member which precludes airflow in either direction or with a one-way valve which permits air to be exhaled from the lung portion while precluding air from being inhaled into the lung portion. In addition, a vacuum may be pulled within the lung portion to be collapsed for collapsing the lung portion and while the lung portion is collapsed the obstructing member may be placed in the air passageway to maintain the lung portion in a permanently collapsed state.

Patent number: 6258100
Filing date: Oct 10, 2000
Issue date: Jul 10, 2001
Inventors: Clifton A. Alferness, Richard Y. Lin, Wilfred E. Jaeger
Assignee: Spiration, Inc.
Primary Examiner: Eduardo C. Robert

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What is claimed is:

1. A method of reducing lung size of a lung, the method including obstructing an air passageway communicating with a portion of the lung, the obstructing step including the step of placing a one-way valve in the air passageway to permit air to be exhaled from the lung portion and to preclude air from being inhaled into the lung portion for collapsing the lung portion.

2. The method of claim 1 including the further steps of inserting a conduit into the air passageway communicating with the lung portion and pulling a vacuum in the lung portion through the conduit.

3. The method of claim 2 wherein the conduit includes an outer surface, and wherein the step of pulling a vacuum includes sealing between the outer surface of conduit and the air passageway.

4. The method of claim 2 wherein the step of placing the one-way valve in the air passageway is performed after the pulling of the vacuum.

5. A method of reducing lung size of a lung, the method including the steps of:

inserting a conduit down a trachea, into a mainstem bronchus, into a bronchial branch, and into a bronchial sub-branch communicating with a lung portion of the lung to be reduced in size;

feeding a one-way valve down the conduit; and

deploying the one-way valve in the bronchial sub-branch so that air is permitted to exit the lung portion while being precluded from entering the lung portion and causing the lung portion to collapse for reducing the size of the lung.

6. The method of claim 5 including the further step of removing the conduit after deploying the one-way valve in the bronchial sub-branch.

7. The method of claim 5 including the further step of pulling a vacuum in the lung portion through the conduit.

8. The method of claim 7 wherein the conduit includes an outer surface, and wherein the step of pulling a vacuum includes sealing between the outer surface of the conduit and the bronchial sub-branch.

9. A method of reducing lung size of a lung, the method including the steps of:

inserting a conduit down a trachea, into a mainstem bronchus, into a bronchial branch, and into a bronchial sub-branch communicating with a lung portion of the lung to be reduced in size;

pulling a vacuum in the lung portion through the conduit to collapse the lung portion; and

deploying an obstructing member in the bronchial sub-branch to preclude air from being inhaled into the lung portion through the bronchial sub-branch.

10. The method of claim 9 wherein the deploying step includes feeding the obstructing member down the conduit and into the bronchial sub-branch.

Lung constriction apparatus and method

2008-01-14T02:43:00.000-08:00

Abstract

A lung constriction device and method provide lung air leak suppression or lung volume reduction. The lung constriction device includes a jacket of flexible material. The jacket is configured to cover at least a portion of a lung. The jacket is further configured to receive the lung portion as it is drawn therein. The jacket may be expandable and held in an expanded condition as the lung tissue is drawn into the jacket. Thereafter, the jacket is permitted to collapse about the lung portion to constrict the lung portion. The jacket may alternatively be nonexpandable. As the lung tissue is drawn into the jacket, it will collapse. Once disposed in the jacket, the jacket constricts the lung tissue to provide leakage suppression or lung volume reduction. The jacket may further be severable so that after the lung portion is drawn into the jacket, the jacket may be severed to section the lung portion.

Patent number: 6328689
Filing date: Mar 23, 2000
Issue date: Dec 11, 2001
Inventors: Hugo X. Gonzalez, Diane M. Muff, William A. Sirokman
Assignee: Spiration, Inc.,
Primary Examiner: Nikita R Veniaminov

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What is claimed is:

1. A lung constriction device comprising a jacket of flexible material configured to cover only a portion of a lung, the jacket having a pair of opened ends to permit the lung portion to be drawn into the jacket and the jacket being dimensioned to constrict and collapse the lung portion.

2. The device of claim 1 wherein the jacket is formed of elastic material.

3. The device of claim 1 wherein the jacket is formed of a mesh material.

4. The device of claim 1 wherein the jacket is formed of one of silicone rubber, polyester, polyurethane, nylon, polytetraflouroethylene, expanded polytetraflouroethylene, polyester and polyurethane, and nylon and polyurethane.

5. The device of claim 1 wherein the jacket is formed of an expandable mesh material.

6. The device of claim 1 wherein the jacket is formed of a severable material to permit the device to be severed intermediate its ends.

7. A lung constriction device comprising a member formed of expandable material, the member being configured for receiving only a portion of a lung when forced into an expanded enlarged condition by an expansion force, and contractible about the lung portion upon release of the expansion force for constricting and collapsing the lung portion.

8. The device of claim 7 wherein the member has a hollow, substantially cylindrical configuration when in a nonexpanded condition.

9. The device of claim 7 wherein the member includes a first opened end for receiving the lung portion.

10. The device of claim 9 wherein the member includes a second opened end for permitting the lung portion to extend through the member.

11. The device of claim 7 wherein the member is formed of one of silicone rubber, polyurethane, expanded polytetraflouroethylene, nylon and polyurethane, and polyester and polyurethane.

12. The device of claim 7 wherein the member is formed of an expandable mesh material.

13. The device of claim 7 wherein the member is formed of a severable material.

14. A method of constricting and collapsing only a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover only a portion of the lung; and

drawing the lung portion into the jacket to constrict and collapse the lung portion.

15. The method of claim 14 wherein the jacket is dimensioned to constrict the lung portion and wherein the drawing step includes collapsing the lung portion while drawing the lung portion into the jacket.

16. The method of claim 15 wherein the drawing step includes physically pulling the lung portion into the jacket.

17. The method of claim 14 wherein the jacket is formed of expandable material and wherein the method includes the further steps of applying an expansion force to the jacket to enlarge the jacket dimensions and releasing the expansion force on the jacket after the drawing step to permit the jacket to collapse about the lung portion for constricting the lung portion.

18. The method of claim 17 wherein the drawing step includes physically pulling the lung portion.

19. The method of claim 14 including the further step of severing the jacket after drawing the lung portion into the jacket to section the lung portion.

20. A method of constricting at least a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover the lung portion;

drawing the lung portion into the jacket; and

positioning the jacket on a mandrel, wherein the lung portion is physically pulled into the mandrel, and the method further including the step of removing the mandrel from the jacket and the lung portion to leave the lung portion constricted in the jacket.

21. A method of constricting at least a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover the lung portion; and

drawing the lung portion into the jacket, wherein the jacket is dimensioned to constrict the lung portion, wherein the drawing step includes collapsing the lung portion while drawing the lung portion into the jacket, and wherein the drawing step includes applying a vacuum suction to the lung portion.

22. The method of claim 21 further including the step of positioning the jacket on a mandrel, wherein the vacuum suction is applied to the lung portion through the mandrel, and the method further including the step of removing the mandrel from the jacket and the lung portion to leave the lung portion constricted in the jacket.

23. The method of claim 21 further including the step of positioning the jacket within a mandrel, wherein the vacuum suction is applied to the lung portion through the mandrel and the jacket to pull the lung portion directly into the jacket, and the method further including the step of removing the mandrel from the jacket.

24. A method of constricting at least a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover the lung portion; and

25. The method of claim 24 wherein the applying step further includes expanding the mandrel after positioning the jacket on the mandrel.

26. The method of claim 24 wherein the drawing step includes applying a vacuum suction to the lung portion through the mandrel to draw the lung portion into the mandrel and wherein the releasing step includes removing the jacket from the mandrel.

27. The method of claim 26 wherein the releasing step further includes terminating the vacuum suction prior to removing the jacket from the mandrel.

28. A method of constricting at least a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover the lung portion; and

29. A method of constricting at least a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover the lung portion; and

drawing the lung portion into the jacket, wherein the jacket is formed of expandable material, wherein the method includes the further steps of applying an expansion force to the jacket to enlarge the jacket dimensions and releasing the expansion force on the jacket after the drawing step to permit the jacket to collapse about the lung portion for constricting the lung portion, and wherein the method further includes the steps of positioning the jacket within a mandrel, and applying a vacuum suction to the lung portion through the mandrel and the jacket to cause the lung portion to be drawn into the jacket and the jacket to be expanded by the lung portion drawn by the vacuum suction.

30. The method of claim 29 wherein the releasing step includes terminating the vacuum suction.

31. A method of reducing the size of a lung, the method including the steps of:

providing a jacket of severable material configured and dimensioned to constrict and seal lung tissue;

drawing a portion of the lung into the jacket to constrict and seal lung tissue of the lung portion; and

severing the jacket to section the lung.

32. The method of claim 31 wherein the jacket includes a pair of opened ends and wherein the drawing step includes drawing the lung portion through the jacket.

33. A method of sectioning body tissue, the method including the steps of:

providing a jacket of severable material configured and dimensioned to constrict and seal the body tissue;

drawing the body tissue into the jacket to constrict and seal the body tissue; and

severing the jacket to section the body tissue.

34. The method of claim 33 wherein the jacket includes a pair of opened ends and wherein the drawing step includes drawing the body tissue through the jacket.

35. A system for sectioning body tissue, the system comprising:

a jacket of severable material configured and dimensioned to constrict and seal the body tissue;

means for drawing the body tissue into the jacket to constrict and seal the body tissue; and

means for severing the jacket to section the body tissue.

36. The system of claim 35 wherein the jacket is formed of an elastic material.

37. A device for use in sectioning body tissue comprising a jacket of severable material configured to cover the body tissue, the jacket having a pair of opened ends to permit the body tissue to be drawn into the jacket and the jacket being dimensioned to constrict and seal the body tissue.

38. The device of claim 37 wherein the jacket is formed of elastic material for collapsing about the body tissue.

39. A lung constriction device comprising a jacket of flexible material configured to cover only a portion of a lung, the jacket having a pair of opened ends to permit the lung portion to be drawn into the jacket and the jacket being dimensioned to constrict, collapse, and disable the lung portion.

40. A lung constriction device comprising a member formed of expandable material, the member being configured for receiving only a portion of a lung when forced into an expanded enlarged condition by an expansion force, and contractible about the lung portion upon release of the expansion force for constricting, collapsing, and disabling the lung portion.

41. A method of constricting, collapsing, and disabling a portion of a lung, the method including the steps of:

providing a jacket formed of flexible material and configured to cover the lung portion; and

drawing the lung portion into the jacket to constrict, collapse, and disable the lung portion.

Lung ventilators

2008-01-14T02:42:00.001-08:00

Abstract

A volume-cycled lung ventilator providing for both spontaneous breathing of a patient and intermittent mandatory ventilation, the invention provides two parallel inspiratory flow paths, one flow path including a demand valve for supplying gas to the patient during spontaneous breathing and the other flow path including a solenoid-operated inspiratory flow valve for providing intermittent mandatory breaths. The invention provides structure capable of adjusting the intervals between mandatory breaths, the volume of each such breath and the flow waveform of each such breath. An expiratory flow path including a fluid operated expiratory flow valve is further provided. A flow rate signal generator in the expiratory flow path acts to sense the rate of exhalation of the patient and is effective to inhibit the opening of the inspiratory flow valve unless the rate of exhalation is below a predetermined value.

Patent number: 4206754
Filing date: May 24, 1977
Issue date: Jun 10, 1980
Inventors: Lawrence A. Cox, John D. Smethers
Assignee: BOC Limited

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What is claimed is:

1. A volume-cycled lung ventilator providing for both spontaneous breathing of a patient connected thereto and intermittent mandatory ventilation, the ventilator comprising:

means defining a first inspiratory flow path and means connecting such flow path at its inlet end to a source of pressurized respirable gas;

means defining a second inspiratory flow path and means connecting such flow path at its inlet end to the source of respirable gas;

means defining an expiratory flow path connected at its outlet end to atmosphere;

patient connection means for supplying respirable gas from the outlet ends of said first and second inspiratory flow paths to a patient, and for supplying gas expired by the patient to the inlet end of said expiratory flow path;

a normally-closed inspiratory flow valve in said first inspiratory flow path and a normally-open expiratory flow valve in said expiratory flow path;

means for operating said inspiratory and expiratory flow valves in synchronization at preselectable intervals to provide intermittent mandatory inspiration through said first inspiratory flow path and expiration through said expiratory flow path, the inspiratory flow valve being open during the inspiratory phase and the expiratory flow valve being closed during the inspiratory phase, the inspiratory flow valve being closed during the expiratory phase and the expiratory flow valve being open during the expiratory phase;

valve means in said second inspiratory flow path to permit spontaneous inspiration through such flow path while expiration is occurring through said expiratory flow path, the valve means comprising a demand valve adapted to permit gas to flow through the second inspiratory flow path from the source to the patient at a flow rate determined by the inspiratory effort of the patient, and a second expiratory valve being provided in said expiratory flow path downstream of said normally open expiratory valve and said demand valve and second expiratory valve are fluid-biased valves and include a regulator connected to the demand valve and second expiratory valve for adjustably biasing both the demand valve and the fluid-biased second expiratory valve so that the expiratory pressure required to stop the supply of gas by the demand valve to the patient is maintained substantially the same as the pressure required to open the second expiratory valve; and,

means for inhibiting the opening of said inspiratory flow valve if the patient is expiring gas at a flow rate above a chosen value, the inhibiting means comprising signal generating means in said expiratory flow path for producing signals representative of the rate of flow of gas expired through said flow path, and means responsive to said signals for inhibiting the opening of said inspiratory flow valve during the exhalation phase.

2. A lung ventilator as claimed in claim 1 wherein means sensitive to pressure in the outlet end of the first inspiratory flow path are effective to close said inspiratory flow valve when said pressure reaches a preset maximum.

Lung ventilator device

2008-01-14T02:40:00.000-08:00

Abstract

Ventilation to a patient is provided in response to patient effort. The free flow of gas from a piston, or similar air source, in response to patient inhalation is detected, the instantaneous rate and volume of flow are measured and the measurements are used as control signals to a drive motor for the piston to move the piston to generate a pressure which is proportional to the sum of measured and suitably amplified rate and volume of flow signals. Since the command signal to the pressure generator only changes subsequent to, and not in advance of, a change in flow and volume, the ventilator is subservient to the patient and provides a proportional assist to patient ongoing breathing effort during inspiration (Proportional Assist Ventilation, PAV).

Patent number: 5107830
Filing date: Mar 30, 1990
Issue date: Apr 28, 1992
Inventor: Magdy Younes
Assignee: University of Manitoba
Primary Examiner: Aaron J. Lewis

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What is claimed is:

1. A method for providing breathing assistance in proportion to patient ongoing inspiratory effort, which comprises:

providing a free flow of gas from a gas delivery system to a patient in response to a pressure gradient generated by patient inspiratory effort,

determining the rate and volume of flow of said gas to said patient,

independently amplifying signals corresponding to said determined rate and volume of flow, and

providing a pressure assist to said gas in proportion to the sum of said determined and amplified rate and volume of flow.

2. The method of claim 1, wherein said pressure assist is determined by the equation:

P.sub.vent =K.sub.1 V+K.sub.2 V

where P.sub.vent is the magnitude of the pressure assist, K.sub.1 is a gain factor applied to a variable ongoing volume signal V and K.sub.2 is a gain factor applied to a variable ongoing flow-signal V.

3. The method of claim 2 wherein non-linear functions are employed in place of K.sub.1 and K.sub.2.

4. The method of claim 1 wherein said pressure assist is determined by the equation:

P.sub.vent =A.multidot.P.sub.mus

where P.sub.vent is the magnitude of the pressure assist, A is an independent factor which determines the proportionally between the pressure assist and patient generated pressure, and P.sub.mus is the estimated instantaneous patient generated pressure determined by the equation:

P.sub.mus =V.multidot.E.sub.rs +V.multidot.R.sub.rs -P.sub.vent

where V is the magnitude of the variable ongoing volume signal, V is the magnitude of the variable ongoing flow signal, E.sub.rs is the elastance of the respiratory system of the patient and R.sub.rs is the resistance against which the respiratory system of the patient is operating.

5. The method of claim 1 wherein said rate and volume of flow are determined by continuously sensing the movement of gas to the patient and generating an electrical signal corresponding in magnitude to each of the sensed rate and volume of gas, continuously separately amplifying each signal to a degree required to provide the pressure assist and providing a summed signal combining each of said amplified signals, and continuously applying said summed signal to said gas delivery system, thereby to provide said pressure assist.

6. The method of claim 5 wherein said movement of gas is sensed to generate an electrical signal corresponding to the rate of flow of gas through a tube connecting said gas delivery system to the patient, and said electrical signal is integrated to provide a further electrical signal corresponding to the volume of flow through said tube.

7. The method of claim 6 wherein said gas delivery system comprises bellows means and an electrical motor operatively connected to said bellows means to generate a pressure corresponding in magnitude to the magnitude of the summed signal applied to said electrical motor.

8. The method of claim 1 wherein said gas delivery system develops negative pressure to assist patient's breathing through the application of negative pressure to a body surface of the patient.

9. The method of claim 1 when used in conjunction with a method of ventilatory assist employing a predetermined relationship of pressure, flow and/or volume versus time, including continuous positive airway pressure (CPAP), intermittent mandatory ventilation (IMV), pressure support ventilation (PSV), and airway pressure release ventilation (APRV).

10. Apparatus for delivering proportional assist ventilation to a patient, comprising:

means for delivering a free flow of gas to said patient in response to patient inhalatory effort,

means operatively connected to said gas delivery means for generating pressure in said free flow of gas in response to an electrical command signal,

detection means for detecting the instantaneous volume and rate of gas flow to said patient and for generating a separate electrical signal corresponding in magnitude to each of said detected values,

means for selectively applying amplification to each of said electrical signals, and

means for generating said electrical command signal to said pressure generating means in proportion to the sum of said amplified electrical signals corresponding in magnitude to said instantaneous rate and volume of flow.

11. The apparatus of claim 10 wherein said gas delivery means comprises bellows means and said gas pressure generating means comprises an electrical drive motor operatively connected to said bellows means.

12. The apparatus of claim 11 wherein said bellows means comprises a rolling seal piston.

13. The apparatus of claim 10, wherein said detection means comprises flow rate sensing means operatively connected to a pipe joining said bellows means to a patient for generating an electrical signal indicative of the instantaneous rate of flow of gas through said pipe and electrical circuit means for generating an electrical signal indicative of volume flow through said pipe from said electrical signal indicative of gas flow rate as said detected instantaneous value of flow volume.

14. The apparatus of claim 13, wherein said means for generating an electrical command signal comprises summing means for summing amplified electrical signals of said volume and gas flow rates, and including means for applying said command signal to said electrical motor means, thereby to provide a ventilatory assist to said patient corresponding to the magnitude of said summed signal.

15. The apparatus of claim 10 adapted to deliver ventilatory assist in the form of negative pressure intended for application to a body surface.

16. The apparatus of claim 10, including electrical circuit means to override said means for generating said electrical command signal to provide an alternative command signal corresponding to an operator predetermined relationship of pressure, flow and/or volume versus time, including continuous positive airway pressure (CPAP), intermittent mandatory ventilation (IMV), pressure support ventilation (PSV), and airway pressure release ventilation (APRV).

Digital moisture meter and method for determining percent weight loss

2008-01-14T01:56:00.000-08:00

Abstract

The digital moisture meter includes means for taring an empty sample pan placed on the balance platen. After the balance has been tared, a small sample is placed in the sample pan and a heat lamp energized. At this same time, the initial weight of the sample is stored in memory and after twenty seconds a first calculation is made to determine the percent weight loss, the value of which is also stored in memory. Subsequent percent weight loss values are calculated and if the latest percent weight loss is greater than the one that has been stored in memory, the stored one is then replaced with the latest value. However, if the latest percent weight loss value is less or equal to the stored value, the stored value is retained in memory for comparison with the next percent weight loss value that is calculated. When the percent weight loss value remains constant for a predetermined number of checks, the stored percent weight loss that has remained constant is then considered to be...

Patent number: 4316384
Filing date: Sep 4, 1979
Issue date: Feb 23, 1982
Inventors: Dennis L. Pommer, Paul E. Coleman
Assignee: General Mills, Inc.

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What is claimed is:

1. A digital moisture meter comprising a balance including a platen for receiving a sample thereon and means for providing a digital signal having a value in accordance with the initial weight of the sample on said platen and also successive later digital signals having digital values representative of later reduced weights of said sample, means for heating said sample to remove moisture therefrom, means for reducing the intensity of said heating means after a predetermined time interval, first means for storing said digital signal having a value representative of the initial weight of said sample, second means for storing said later digital signals having a value representative of a subsequent reduced weight, each of said later digital signals being successively stored in said second storing means, calculating means responsive to the value of said digital signal stored in said first storing means and the value of said digital signal stored in said second storing means at a given time for providing a digital signal having a value representative of the percent weight loss for each successively stored later digital signal, third means for storing one of said digital signals having a value representative of percent weight loss, fourth means for storing a later digital signal having a value representative of a later percent weight loss, means for comparing the value of said one digital signal stored in said third storing means with the value of the digital signal stored in said fourth storing means and for substituting the digital signal stored in said fourth storing means for the one stored in said third storing means if greater in value than the one already stored in said third storing means, means for displaying the value of said digital signal stored in said third storing means if the value stored in the fourth storing means is less than or equal to the signal stored in said third storing means, and means for disconnecting said heating means only after a predetermined number of successive digital signals stored in said fourth means have a value less than or equal to the digital signal stored in said third storing means and have thus denoted a stabilized weight loss condition.

2. A digital moisture meter comprising balance means including a platen for receiving a sample therein and means for producing digital signals having values in accordance with the weight of the sample on said platen, means above said platen for heating said sample, first and second registers, means for forwarding a first digital signal having a value representative of the initial weight of said sample to said first register for storage therein and for subsequently forwarding successive digital signals having values representative of later weights of said sample to said register for storage therein, calculating means for receiving the digital signals stored in said first and second registers to provide successive digital signals each of which has a value representative of the percent weight loss of said sample for each of said successive digital signals, third and fourth registers, said fourth register storing said digital signals having values representative of the percent weight loss, and comparing means connected to said third and fourth registers for transferring the latest digital signal stored in said fourth register to said third register when the value of the latest digital signal stored in said fourth register is greater than the digital signal stored in said third register and in which the digital signal stored in said third register is retained in said third register when said digital signal in said fourth register is less than or equal to the digital signal stored in said third register, means for counting the number of times the latest digital signal stored in said fourth register is less than or equal to the digital signal stored in said third register, and means responsive to said last-mentioned means for disabling said heating means after said last-mentioned means has reached a predetermined count and has thus denoted a stabilized weight loss condition.

3. A method of determining the percent moisture loss in a relatively small sample comprising the steps of obtaining a first digital signal having a value representative of the initial weight of said sample, storing said first digital signal, subjecting said sample to a source of heat, obtaining a second digital signal having a value representative of the weight of said sample at a later time, storing said second digital signal, calculating from said first and second digital signals a third digital signal having a value representative of the percent weight loss, storing said third digital signal, obtaining a fourth digital signal having a value representative of the weight of said sample at a still later time, storing said fourth digital signal, calculating from said first and fourth digital signals a fifth digital signal having a value representative of the percent weight loss occurring at said still later time, comparing said third and fifth digital signals to ascertain whether the fifth digital signal has a value greater than that of said third digital signal, or less than or equal to the value of said third digital signal, continuing to subject said sample to said heat source if the value of said fifth digital signal is greater than the value of said third digital signal, and removing said heat source when the value of said fifth digital signal is equal to a predetermined value.

4. A method in accordance with claim 3 including the steps of obtaining additional third and fifth digital signals and determining when a predetermined number of fifth digital signals are less than or equal to a third digital signal, said predetermined number of fifth digital signals when less than or equal to a third digital signal denoting a stabilized weight loss condition.

Methods for preventing weight loss, reduction in weight gain, and anorexia

2008-01-14T01:53:00.000-08:00

Abstract

Animal feed or human food which contains added conjugated linoleic acids (CLA) can enhance growth and prevent anorexia and weight loss due to immune stimulation (e.g., endotoxin exposure) and the adverse effects of catabolic hormones (i.e., IL-1). Methods of treatment using CLA also are disclosed.

Patent number: 5430066
Filing date: Apr 29, 1992
Issue date: Jul 4, 1995
Inventors: Mark E. Cook, Michael W. Pariza
Assignee: Wisconsin Alumni Research Foundation
Primary Examiner: K. Weddington

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What is claimed is:

1. A method of preventing weight loss, reduction in weight gain or anorexia in an animal caused by immune stimulation of the animal by endotoxin, said method comprising administering orally or parenterally to said animal a safe amount of a member selected from a conjugated linoleic acid, free linoleic acid, salts thereof and mixtures thereof, said amount being effective to prevent the weight loss, reduction in weight gain or anorexia caused by the immune stimulation.

2. A method of claim 1 in which the animal is a bird.

3. A method of claim 1 in which the conjugated linoleic acid is selected from 9,11-octadecadienoic acid and 10,12-octadecadienoic acid.

4. A method of alleviating the adverse catabolic effects produced by a product of the immune system which is released after immune stimulation of an animal by endotoxin, said method comprising orally or parenterally administering to said animal a safe amount of a member selected from a conjugated linoleic acid, free linoleic acid, salts thereof and mixtures thereof, said amount being effective to alleviate said adverse catabolic effects produced by a product of the immune system.

5. A method of claim 4 in which the conjugated linoleic acid is selected from 9,11-octadecadienoic acid and 10,12-octadecadienoic acid.

6. A method of alleviating the adverse catabolic effects produced by interleukin-1, said method comprising administering orally or parenterally to an animal a safe amount of a member selected from a conjugated linoleic acid, free linoleic acid, salts thereof and mixtures thereof, said amount being effective to alleviate said adverse catabolic effects.

7. A method for improving an animal food so as to prevent the weight loss, the reduction in weight gain or the anorexia which can be caused by immune stimulation of an animal by endotoxin, said method comprising adding to an animal food a member selected from 9,11-octadecadienoic acid; 10, 12-octadecadienoic acid; and mixtures thereof, so that the food contains about 0.1% to about 2.0% by weight of the food, said amount being effective when the food is fed to an animal to prevent the weight loss, the reduction in weight gain or the anorexia caused by immune stimulation.

Device and method of causing weight loss using removable variable volume

2008-01-14T01:51:00.000-08:00

Abstract

A method and apparatus for causing weight loss in obese humans by occupying a segment of the stomach volume using a variable volume bladder filled with fluid. The bladder is inserted into the upper part of the stomach including the fundus through a percutaneous endoscopic gastrostony tube, which was non-surgically placed to create a permanent channel to the stomach. The inserted bladder is filled and emptied using a filling system for pumping fluid in and out of the bladder according to a predetermined scheme. The filling system comprises a reversible pump, a two-way valve connected to the filling tube, an electronic control means for automatically controlling the action of the filling system, and a battery. The electronic control means is connected to a plurality of sensors placed on the human body to detect digestion cycle and hemodynamic parameters. The electronic control means collects information detected by the sensors, governs the filling system according to the obtained...

Patent number: 5259399
Filing date: Mar 2, 1992
Issue date: Nov 9, 1993
Inventor: Alan Brown
Primary Examiner: J. P. Lacyk

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What is claimed is:

1. A method of causing weight loss in obese humans by occupying a segment of the stomach volume using an inflated bladder, said method comprising the steps of:

(a) measuring the volume and location of the stomach including the fundus by radiological techniques,

(b) selecting a bladder contoured in size and shape to substantially occupy the fundus or the body of the stomach measurement,

(c) introducing by percutaneous endscopic techniques a percutaneous endoscopic gastrostomy (P.E.G.) tube to establish access from the outside to the body of the stomach through the abdominal wall,

(d) inserting said bladder through said percutaneous endoscopic gastrostomy tube into the stomach so the size and shape of said bladder, cooperating with the position of placement of said gastrostomy tube, maintains said bladder in the upper part of the stomach including the fundus, and

(e) filling and emptying said bladder with fluid repeatedly over time through a filling tube that extends through said gastrostomy tube, in the manner that said bladder when filled occupies a large portion of said stomach to cause a feeling of satiety, thereby to achieve decreased consumption of food by a patient, and said emptying of said bladder provides periods of reduced trauma to the stomach to promote the patient's health and feeling of well being, said bladder capable of being withdrawn from said stomach through said P.E. G. tube to enable inspection and replacement and to enable ready access to the lumen of the stomach through the abdominal wall.

2. The method of claim 1 wherein said measurement of the volume and location of said stomach is conducted by employing an air contrast upper GI series, including the making of frontal and lateral projection radiographs.

3. The method of claim 1 wherein said measurement of the volume and location of said stomach is conducted by employing computerized tomography.

4. The method of claim 1 wherein said introduction of said P.E.G. tube in said obese person comprises the steps of:

(a) inspecting said stomach of said obese person using both an endoscope and a fluoroscope, said endoscope introduced into the stomach through the mouth down through the esophagus,

(b) establishing a location for said gastrostomy tube placed to maintain said bladder in the desired position,

(c) when a needle, forming a puncture in the abdomen at said location, the needle passing through the thick layer of abdominal fat of said obese person, and via said puncture inserting a guidewire from outside through the abdominal wall into said fundus of said stomach, grasping the distal portion of said guidewire using said introduced endoscope and by pulling said endoscope out of the mouth extracting the distal end of said guidewire out of the mouth while the proximal end of said guidewire is held outside of the puncture formed in the abdomen,

(d) placing said gastrostomy tube through the abdominal wall by attaching said gastrostomy tube to the distal portion of said guidewire while said portion extends out of the patient's mouth and pulling on the proximal end of said guidewire until said percutaneous endoscopic gastrostomy tube passes through the esophagus, stomach, and abdominal wall to the outside, and

(e) securing said sealing said placed gastrostomy tube on the stomach wall and on the abdominal wall and cutting said gastrostomy tube to the appropriate length.

5. The method of claim 1 further comprising the steps of:

(a) removing said bladder from the stomach through said gastrostomy tube,

(b) inserting an endoscope into the stomach through said gastrostomy tube in order to examine the gastric wall for trauma and ulceration, and

(c) re-inserting said bladder through said gastrostomy tube into the stomach so the size and shape of said bladder, cooperating with the position of placement of said gastrostomy tube, again maintains said bladder in the fundus or the body of the stomach.

6. The method of claim 1 wherein said repeated filling or emptying said bladder is automatically controlled by a filling system.

7. The method of claim 1 further including the steps of:

(a) detecting condition of said obese patient with sensors measuring indicators of digestion and hemodynamic parameters,

(b) transmitting information from said sensors to an electronic control means linked to a filling system used for filling and emptying said bladder, and

8. The method of claim 6 wherein said filling and emptying of said bladder being performed by a reversible air pump forcing air into said bladder or releasing air from said bladder as governed by said electronics control means receiving input from said sensors and operating according a predetermined procedure.

9. The method of claim 6 further including manually inducing said filling or emptying of said bladder by overriding said electronics control means connected to said filling system.

10. A medical device for treatment of obese humans by occupying a segment of the stomach volume comprising

a bladder sized and shaped to substantially occupy the fundus or the body of the stomach,

a filling tube connectable to said bladder for repeated filling and emptying of said bladder located in the stomach of said obese humans, and

said filling tube and said bladder collapsed in condition to pass through a percutaneous endoscopic gastrostomy (P.E.G.) tube into the stomach, said filling tube having sufficient lengths to extend proximally through said gastrostomy tube to enable said filling and emptying of said bladder.

11. The device of claim 10 including a stylet extending into the bladder to enable thrusting of the collapsed bladder through said P.E.G. tube into the stomach.

12. A system for automatically filling and emptying a bladder positioned in the stomach to enable weight loss in obese humans, said system being connected to a bladder through a filling tube, said system comprising

(a) a valve adapted to control amount of fluid introduced or released from said bladder through said filling tube,

(b) a reservoir of fluid for introduction into said bladder through said valve, and

(c) an electronics control means for controlling filling and emptying said bladder with said fluid according to a predetermined set of criteria.

13. A system for automatically filling and emptying a bladder positioned in the stomach in order to cause weight loss in obese humans, said system being connected to said bladder through a filling tube, said system comprising

(a) a valve for controlling amount of fluid introduced or released from said bladder through said filling tube,

(b) a pump for introducing air into said bladder through said valve, and

(c) an electronics control means for controlling filling and emptying said bladder with said fluid according to a predetermined set of criteria.

14. The system of claim 12 or 13 further comprising a plurality of sensors connected to provide information to said electronic control means,

said sensors being placed in the human body to monitor indicators of digestion or hemodynamic parameters and said electronic control means adapted to control said filling and emptying of said bladder in accordance with digestive cycles corresponding to said indicators.

15. A system of claim 12 or 13 wherein said electronic control means is adapted to keep an electronic record of inflation and deflation times and volumes of fluid passed through said valve.

Weight loss management system

2008-01-14T01:49:00.000-08:00

Abstract

A weight loss management system utilizes a computer analysis of a participant's past medical history, eating habits, body measurements, exercise level and taste preferences to provide a menu of a specified number of calories to maintain a reasonable weight. The system provides consultation with a dietition in order for a participant to recognize the deficiencies in the past diet. The system further provides consultation to effect behavior modification of the participant by offering instruction in nutrition, exercise and proper cooking techniques.

Patent number: 4951197
Filing date: Feb 10, 1989
Issue date: Aug 21, 1990
Inventor: Gilbert Mellinger
Assignee: AMC of America
Primary Examiner: Gail O. Hayes

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1. A method of individualized weight management comprising:

(a) obtaining a medical history of a subject and determining the existence of any physiological abnormalities;

(b) obtaining a present physical profile of said subject said profile including data as to sex, physical measurements for determining frame size such as bone or wrist measurements, weight and height of said subject;

(c) obtaining specific information of recent food items caused by said subject and recent level of physical activity in terms of the number of calories burned per pound or per kilogram per day;

(d) entering data obtained from steps (a)-(c) into a computer for comparison with predetermined standards of food consumption given a specified sex, frame size, weight, height and said recent level of physical activity in terms of the number of calories burned per pound or per kilogram per day in relation to an ideal weight;

(e) obtaining a computer analysis of the comparison of the results of step (d) with the caloric and nutritional requirements for said subject at said ideal weight at said recent level of physical activity and employing said computer to calculate the deviation of the current eating habits from said requirements for said subject;

(f) computing with said computer to determine whether a subject should be placed on an intermediate diet plan having a target weight above an ideal target weight by utilizing the formula:

(A.times.C)-(B.times.C)=D

wherein

A represents the actual current weight of the subject in pounds or kilograms;

B represents the ideal weight in the same unit of measure as A and as determined by said compute analysis;

C represents said activity level of said subject in terms of the number of calories burned per pound or per kilogram per day in which said activity level is represented by the values of 11 calories per pound for sedentary activity; the value of 13 calories per pound for light activity; the value of 15 calories per pound for moderate activity and the value of 20 calories per pound for vigorous physical activity;

D is a calculated number which if greater than 1,000 calories indicates said subject should be placed on a diet in which said target weight should be initially set above said ideal target weight;

(g) providing said subject with information as to a weight control program in which the eating habits are modified by selectively placing the caloric and nutritional intake at a targeted weight substantially at or above the value corresponding to said ideal weight;

(h) providing said subject with behavior modification instruction to alternatives to past food consumption wherein said behavior modification is selected from the group consisting of cooking, eating, exercise, nutrition or a combination thereof;

(i) providing said subject with periodic goals for achieving said behavior modification;

(j) providing periodic consulation with said subject and review to ascertain the attainment of goals resulting from step (i) and providing additional goals; and (k) following up said consulation and review with periodic computer analysis of said ideal with additional data gathered including the changes in weight and food consumption of said subjects in relation to said predetermined standards.

2. The method of individualized weight management of claim 1 wherein said step of obtaining said medical history includes historical information as to blood pressure, heart anomalities, chronic diseases and pregnancy.

3. The method of individualized weight measurement of claim 2 wherein said step of obtaining said physical profile and said physical measurements for determining frame size comprises the measurement of the circumference of the wrist of said subject.

4. The method of individualized weight measurement of claim 1 wherein said step of obtaining specific information on recent food items consumed includes data on fat, carbohydrate protein and caloric intake in relation to the number of calories burned per pound or per kilogram per day.

5. The method of individualized weight management of claim 1 wherein said step of following up said consultation with additional data includes periodic updating as to changes in nutrient intake of said subject compared with predetermined standards.

6. The method of individualized weight management of claim 5 wherein said step of following up said consultation and review with periodic computer analysis further includes a print-out of the sources of calories consumed.

7. The method of individualized weight management of claim 6 wherein said print-out of said sources of calories consumed includes catagories listing the amounts of protein, carbohydrates, fat and alcohol as separate calorie sources.

8. The method of individualized weight management of claim 1 wherein said step of following up said consultation with additional data includes periodic updating as to changes in the physical activity level of said subject.

9. The method of individualized weight management of claim 1 wherein said step of following up said consultation with additional data includes computer analysis of the sources of calories consumed which are then compared with predetermined standards for sources of calories.

10. The method of individualized weight management of claim 1 wherein said step of obtaining specific information of recent food items consumed by said subject includes information as to past food consumption and data regarding food item preferences.

11. The method of individualized weight management of claim 10 wherein said step of obtaining specific information of recent food items consumed by said subject includes information regarding food item taste preference.

12. The method of individualized weight management of claim 1 wherein said step of behavior modification instruction includes instruction in selecting quantity and types of foods.

13. The method of individualized weight management of claim 1 wherein said step of behavior modification instruction includes instruction for physical exercise.

14. The method of individualized weight management of claim 1 wherein said step of behavior modification includes modifying cooking habits to waterless and greaseless cooking.

15. A weight management method for attaining an ideal weight comprising:

(a) obtaining medical history of a subject to enumerate specific potential physiological abnormalities;

(b) obtaining a physical profile of said subject by means of obtaining data on height, sex, frame size, and weight;

(c) obtaining information as to physical activity level and past food consumption over a specified period of time in terms of types of food, nutritional value, and the number of calories burned per pound per day;

(d) inputting data obtained from the information obtained in steps (a)-(c) to a computer for comparison with predetermined standards;

(e) ascertaining the number of calories said subject is above an ideal calorie and nutritional intake level;

(f) obtaining a computer analysis of the current calorie and nutritional level of said subject in relation to said predetermined standards;

(g) providing an intermediate calorie level above said ideal calorie and nutritional intake level for a predetermined period of time where the number of calories said subject is above said ideal calorie and nutritional level is greater than 1000 calories;

(h) providing said subject with information as to a modification of eating patterns to selectively place said subject either at said ideal calorie and nutritional level, above said ideal calorie and nutritional intake level, or not more than 300 calories below said ideal calorie and nutritional level:

(i) providing said subject with behavior modification instruction to alternatives to past food consumption wherein said behavior modification includes one or more changes selected from the group consisting of cooking, eating, nutritional and exercise habits;

(j) providing said subject with goals for achieving behavior modification on a periodic basis;

(k) providing periodic consultation and review with said subject to ascertain the attainment of goals of step (h) and providing additional goals; and

(l) following-up the consultation and review with a further computer analysis of the present weight and food consumption of said subject in relation to said predetermined standards.

16. The weight management method of claim 15 wherein said step of ascertaining the number of calories said subject is above said ideal calorie and nutritional intake level is calculated by said computer.

17. The weight management method of claim 16 wherein said step of obtaining information as to physical activity level and past food consumption includes obtaining information as to food taste preference.

18. The weight management method of claim 15 wherein said step of behavior modification includes modifying at least one member of the group consisting of cooking, eating and exercise habits.

19. The weight management method of claim 18 wherein said step of modifying said cooking habits includes greaseless and waterless cooking.

20. The weight management method of claim 15 wherein said step of behavior modification consists of changing exercise habits.

21. The weight management method of claim 15 wherein said step of obtaining information as to physical activity level and past food consumption includes listing amounts of protein, carbohydrates, fat and alcohol as separate calorie sources in relation to the number of calories burned per pound per day.

Weight loss composition for burning and reducing synthesis of fats

2008-01-14T01:48:00.000-08:00

Abstract

The present invention involves a dietary supplement that can be used as a weight loss composition. The composition comprises of an essentially dry mixture of chromium, L-carnitine, gamma-linolenic acid, (-) hydroxycitric acid, choline, inositol, antioxidants and herbs. The preferred antioxidants are Coenzyme Q10 and the herbs are ginkgo biloba leaves. The essentially dry mixture can be prepared as a beverage and delivered enterally. The present invention also involves a method for inducing weight loss in a mammal. The method involves administering to a mammal, preferably a human, a weight loss inducing effective amount of the above described essentially dry mixture. The weight loss inducing effective amount of the above composition is administered daily in at least two separate portions of 7.325 grams each.

Patent number: 5626849
Filing date: Jun 7, 1995
Issue date: May 6, 1997
Inventors: Carl W. Hastings, David J. Barnes
Assignee: Reliv International, Inc.

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What is claimed is:

1. A weight loss composition comprising:

250 to 500 mg (-) hydroxycitric acid;

50 to 125 mg L-carnitine;

25 to 100 mcg Chromium;

25 to 100 mg Choline;

25 to 100 mg Inositol;

25 to 100 mg Gamma-Linolenic Acid;

15 to 75 mg herbs; and

5 to 30 mg antioxidants.

2. The composition of claim 1 wherein the herbs are ginkgo biloba leaves and the antioxidants are Coenzyme Q10.

3. The composition of claims 1 or 2 further comprising 0.15 to 0.35 g soy lecithin, 0 to 10 g carbohydrates, and 0.1 to 0.5 g oat flour.

4. The composition of claim 3 where the carbohydrates are maltodextrin and the oat flour is hydrolyzed.

5. A weight loss composition comprising:

250 to 500 mg (-) hydroxycitric acid;

50 to 125 mg L-carnitine;

25 to 100 mcg Chromium;

25 to 100 mg Choline;

25 to 100 mg Inositol;

25 to 100 mg Gamma-Linolenic Acid;

15 to 75 mg Ginkgo Biloba Leaves; and

5 to 30 mg Coenzyme Q10.

6. The composition of claim 5 further comprising 0.15 to 0.35 soy lecithin, 0 to 10 g carbohydrates, and 0.1 to 0.5 g oat flour.

7. The composition of claim 6 where the carbohydrates are maltodextrin and the oat flour is hydrolyzed.

8. A weight loss composition comprising:

375 mg (-) hydroxycitric acid;

75 mg L-Carnitine;

50 mcg Chromium;

50 mg Choline;

50mg Inositol;

501 mg Gamma-Linolenic Acid;

b 33 mg Ginkgo Biloba Leaves; and

15 mg Coenzyme Q10.

9. The composition of claim 8 further comprising 0.18 g soy lecithin, 5.3 g carbohydrates, and 0.33 g oat flour.

10. An aqueous beverage composition to facilitate weight loss comprising:

250 to 500 mg (-) hydroxycitric acid;

50 to 125 mg L-carnitine;

25 to 100 mcg Chromium;

25 to 100 mg Choline;

25 to 100 mg Inositol;

25 to 100 mg Gamma-Linolenic Acid;

15 to 75 mg Ginkgo Biloba Leaves; and

5 to 30 mg Coenzyme Q10.

11. The aqueous beverage composition of claim 10 further comprising 0.15 to 0.35 g soy lecithin, 0 to 10 g carbohydrates, and 0.1 to 0.5 g oat flour.

12. The aqueous beverage composition of claim 11 wherein the carbohydrates are maltodextrin and the oat flour is hydrolyzed.

13. A method of inducing weight loss in a mammal, comprising administering to said mammal a weight loss inducing effective amount of the composition of claim 1.

14. The amount of claim 13 wherein the weight loss inducing effective amount is administered at least daily in two separate portions of 7.325 grams each.

15. A method of inducing weight loss in a mammal, comprising administering to said mammal a weight loss inducing effective amount of the composition of claim 5.

16. The method of claim 15 wherein the weight loss inducing effective amount is administered daily in two separate portions of 7.325 grams each.

17. A method of inducing weight loss in a mammal, comprising administering to said mammal a weight loss inducing effective amount of the composition of claim 8.

18. The method of claim 17 wherein the weight loss inducing effective amount is administered at least daily in two separate portions of 7.325 grams each.

19. A method of inducing weight loss in a mammal, comprising administering to said mammal a weight loss inducing effective amount of the composition of claim 10.

20. The method of claim 19 wherein the weight loss inducing effective amount is administered daily in at least two separate portions of 7.325 grams each.

Weight loss device and method

2008-01-14T01:46:00.000-08:00

Abstract

The intra-gastric weight loss system apparatus and method of the present invention includes an intra-gastric elastomeric rubber balloon with self-sealing fill valve, to be placed and retrieved without surgery. As a benign space-occupying device, it will decrease gastric capacity to the point that saiety (the feeling of fullness) will occur after very little food has been consumed. Thus, the advantages of gastric and intestinal by-pass surgery will be realized, without surgery and the many resulting complications thereof. The elastomeric balloon is inflated with a liquid, preferably a saline solution containing an X-ray contrast media. The balloon is placed in a person's stomach by passing a naso-gastric tube through the mouth. The N-G tube has a previously placed nylon pull string through the lumen and back up the exterior. After this, a metal stylette is run down the lumen to very near the end of the N-G tube. The rolled up balloon with fill tube attached is inserted into a...

Patent number: 4485805
Filing date: Aug 24, 1982
Issue date: Dec 4, 1984
Inventor: Lawrence H. Foster, Jr.
Assignee: Gunther Pacific Limited of Hong Kong

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What is claimed is:

1. Apparatus for use in achieving a loss of weight in an overweight person comprising:

an inflatable device;

means for placing said device within the stomach of the person without surgery;

additional means for inflating said device with liquid after it has been placed in the person's stomach;

further means for allowing both said placing means and said inflating means to be completely removed from the person so as to leave the inflated device floating in the person's stomach; and said further means including

a pull string having a rollable finger cot attached at one end, and a releasable, self-closing fill valve as part of the inflatable device.

2. Apparatus as set forth in claim 1, wherein said releasable, self-closing fill valve receives one end of a flexible fill tube prior to the device being rolled up and associated with the extended finger cot for placing of the inflatable device in the person's stomach, said fill tube being connected to liquid supply means so that the inflatable device can be inflated with liquid after it has been placed in the person's stomach, and such inflation in turn effecting rolling up and disengagement of said finger cot from the device.

3. The method of placing a gastric cavity filling device within an obese person's gastric cavity without any surgery, comprising the steps of:

providing an inflatable device in deflated form;

attaching a fill tube to the inflatable device;

inserting a hollow tube containing a string therethrough into the person's mouth, esophagus and gastric cavity;

releasably attaching the deflated device with fill tube attached to one end of the string;

pulling the other end of the string to pull the deflated device into the person's gastric cavity;

inflating the deflated device through the fill tube and after suitable inflation of the device;

removing all the placing apparatus so that the inflated device remains free-floating in the person's gastric cavity without any attachments thereto.

4. The method of claim 3, with the further steps of:

inserting a stiffener member into the hollow tube containing the string therethrough prior to the step of pulling the string.

5. The method of claim 4, with the additional step of using liquid containing an X-ray opaque substance therein for inflating the device.

Weight loss control system

2008-01-14T01:42:00.000-08:00

Abstract

A control for a batch bin and a continuous loss bin system having a separate weight measuring device for each bin whose sum at transfer is used to establish continuously digitally desired weights at fixed intervals to be compared with the actual weight in the continuous loss bin to provide an error signal for a continuous feeder.

Patent number: 4111336
Filing date: Apr 14, 1977
Issue date: Sep 5, 1978
Inventors: William H. Ward, Henry F. Henderson, Jr., Kenneth H. Kardux
Assignee: H. F. Henderson Industries

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What is claimed is:

1. In a material feeding apparatus having a first storage means for storing a preselected weight of material, a transfer means at the outlet of said first storage means, a second storage at the outlet of said transfer means for storing material, a continuous feed means at the outlet of said second storage means and control means for operating said transfer means and said continuous feed means the improvement being said control means which comprises:

first measuring means for measuring the weight of material in said first storage means;

second measuring means for continuously measuring the weight of material in said second storage means;

logic means for providing a control signal for said continuous feed means as a function of the weight measurement of said second measuring means relative to the sum of weight measurements of said first and second measuring means prior to opening of said transfer means.

2. The material feeding apparatus according to claim 1 wherein said logic means includes digital weight prediction means responsive to weight measurements of said first and second measuring means to provide desired weights at specific time intervals and a means for comparing said desired weights and weight measurements of said second measuring means to produce said control signal for said continuous feed means.

3. The material feeding apparatus according to claim 2 wherein said weight prediction means includes means for digitally storing weight measurments from said first and second measuring means immediately prior to said transfer means opening and means for decrementing said storing means to provide said desired weights.

4. The material feeding apparatus according to claim 2 wherein said weight prediction means includes a down counter for storing sum of weight measurements from said first and second measuring means, means for counting down said counter at a fixed rate and a digital to analog converter for converting the contents of said down counter to said desired weight for a desired feeding rate.

5. The material feeding apparatus according to claim 4 wherein said comparing means includes an analog comparator for comparing said desired weight with the weight measurement from said second measuring means and said countdown means includes a variable reference for modifying said desired weight as a function of a desired feeding rate.

6. The material feeding apparatus according to claim 2 wherein said comparing means includes a sample and hold means for holding said control signal for said continuous feed means at a fixed value during said transfer.

7. The material feeding apparatus according to claim 6 including timing means responsive to a low weight signal from said second measuring means for activating said transfer means and said sample and hold means for a fixed period of time.

8. A control system for material feeding apparatus comprising:

first means for measuring the weight of a batch supply;

second means for measuring the weight of a continuous loss supply;

means for transferring said batch supply to said continuous loss supply;

logic means for continuously providing a desired weight signal at fixed intervals based on the sum of the signals of said first and second measuring means immediately prior to said batch supply being transferred to said continuous loss supply; and

means for providing a weight error signal responsive to said desired weight signal and said signal of said second measuring means.

9. A control system according to claim 8 wherein said logic means includes means for digitally storing the sum of signals from said first and second measuring means immediately prior to said transfer and means for continuously decrementing said digital storage means at a rate sufficient to provide desired weight signals at said fixed intervals.

10. A control system according to claim 9 wherein said logic means further includes a digital to analog converter for converting the decremental sum to an analog desired weight signal and wherein said error means includes analog means for comparing said desired weight signal with the weight signal from said second measuring means to provide said weight error signals.

11. A control system according to claim 10 wherein said error means includes means connected to the output of said analog comparing means for sampling the output of said analog comparing means and holding the sampled value during said transfer.

12. A control system according to claim 9 wherein said digital storage means includes a down counter and said logic means includes means for summing said signals from said first and second measuring means and means for inserting the sum from said summing means to said digital storage means at a preselected value of said signal of said second measuring means.

13. A control system according to claim 12 wherein said decrementing means includes a means for producing pulses and means for accumulating said pulses to produce said decrementing at said fixed interval, and said inserting means receives pulses from said accumulating means to insert said sum between one of said fixed intervals.

14. A control system according to claim 12 wherein said error means includes means for sampling and holding said weight error signal and wherein said logic means includes a timing means for providing a batch transfer signal and a sample and hold signal for a fixed period of time in response to said preselected value of said signal of said second measuring means.

Retinoic acid derivatives in the treatment of acne

2008-01-11T14:57:00.000-08:00

Abstract

Esters and amides of all-trans-retinoic acid are disclosed which are useful for the treatment of acne.

Patent number: 4126693
Filing date: Aug 5, 1977
Issue date: Nov 21, 1978
Inventors: Robert J. Gander, John A. Gurney
Assignee: Johnson & Johnson

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What is claimed is:

1. N-(3,4-Methylenedioxyphenylmethyl)-all-trans-retinamide.

2. A pharmaceutical composition for the treatment of acne by topical application which comprises an effective acne-treatment amount of N-(3,4-methylenedioxyphenylmethyl)-all-trans-retinamide admixed with a pharmaceutically-acceptable vehicle.

3. The composition of claim 2 wherein the N-(3,4-methylenedioxyphenylmethyl)-all-trans-retinamide comprises from about 0.01% to about 0.5% by weight of the composition.

4. The composition of claim 3 wherein the N-(3,4-methylenedioxyphenylmethyl)-all-trans-retinamide comprises from about 0.05% to about 0.2% by weight of the composition.

5. The composition of claim 2 wherein the vehicle is a mixture selected from the group consisting of propylene glycolethanol and propylene glycol-ethanol-chloroform.

6. A method for treatment of acne in a subject requiring such treatment which comprises topical application to the acne site of said subject of a composition comprising an effective acne-treatment amount of N-(3,4-methylenedioxyphenylmethyl)-all-trans-retinamide admixed with a pharmaceutically-acceptable topical vehicle.

7. The method of claim 6 wherein the N-(3,4-methylenedioxyphenylmethyl)-all-trans-retinamide comprises from about 0.01% to about 0.5% by weight of the composition.

8. The method of claim 7 wherein the N-(3,4-methylenedioxyphenylmethyl)-all-trans-retinamide comprises from about 0.05% to about 0.2% by weight of the composition.

9. The method of claim 6 wherein the vehicle is a mixture selected from the group consisting of propylene glycolethanol and propylene glycol-ethanol-chloroform.

Topical treatment of acne with cephalosporins

2008-01-11T14:55:00.000-08:00

Abstract

A method and composition for topically treating acne and acneiform dermal disorders includes applying an amount of a cephalosporin antibiotic effective to treat the acne and acneiform dermal disorders. The antibiotic is blended with a carrier suitable for topical application to dermal tissues. The carrier is selected from the group consisting of an aqueous liquid, an alcohol base, a water soluble gel, a lotion, an ointment, a nonaqueous liquid base, a mineral oil base, a blend of mineral oil and petrolatum, liposomes, a time-release patch, and a liquid-absorbed wipe. The cephalosporin can also be combined with benzoyl peroxide in a gel carrier.

Patent number: 5409917
Filing date: Sep 24, 1993
Issue date: Apr 25, 1995
Inventors: Howard N. Robinson, Neil F. Martin
Assignees: Marvin S. Towsend, Leonard Bloom

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What is claimed is:

1. A method of treating a human being for acne which comprises administering to the human being an amount of a composition consisting essentially of a cephalosporin antibiotic active ingredient selected from the group consisting of cefaclor, cefadroxil, cefamandole nafate, cefazolin, cefixime, cefmetazole, cefonioid, cefoperazone, ceforanide, cefotanme, cefotaxime, cefotetan, cefoxitin, cefpodoxime proxetil, ceftazidime, ceftizoxime, ceftriaxone, ceftriaxone moxalactam (a 1-oxa-beta-lactam), cefuroxime, cephalexin, cephalosporin C, cephalosporin C sodium salt, cephalothin, cephalothin sodium salt, cephapirin, cephradine, the 1-acetyloxy ethyl ester of cefuroxime (cefuroxime-axetil), dihydratecephalothin, moxalactam, and loracarbef and a pharmaceutical carrier, applied directly to affected dermal tissues, effective to treat the acne wherein said pharmaceutical carrier is a mixture of water and a water-miscible alcohol in amounts ranging from 42.2% to 99.5% of the composition.

2. The method described in claim 1 wherein the cephalosporin antibiotic is present in a range of from 0.5% to 10% by weight of the composition.

3. The method described in claim 1 wherein said water-miscible alcohol is ethyl alcohol in a weight percent range spanning 35% to 98.5%.

4. The method described in claim 1 wherein said water-miscible alcohol is isopropyl alcohol in a weight percent range spanning 4% to 80%.

5. The method described in claim 1 wherein said water-miscible alcohol is propylene glycol in a weight percent range spanning 3% to 26.8%.

6. The method described in claim 1 wherein said water is in a weight percent range spanning 9% to 95%.

7. The method described in claim 1 wherein said water-miscible alcohol is in a weight percent range spanning 11.2% to 90%.

8. A method of treating a human being for acne which comprises administering to the human being an amount of a composition consisting essentially of a cephalosporin antibiotic active ingredient selected from the group consisting of cefaclor, cefadroxil, cefamandole nafate, cefazolin, cefixime, cefmetazole, cefonicid, cefoperazone, ceforanide, cefotanme, cefotaxime, cefotetan, cefoxitin, cefpodoxime proxetil, ceftazidime, ceftizoxime, ceftriaxone, ceftriaxone moxalactam (a 1-oxa-beta-lactam), cefuroxime, cephalexin, cephalosporin C, cephalosporin C sodium salt, cephalothin, cephalothin sodium salt, cephapirin, cephradine, the 1-acetyloxy ethyl ester of cefuroxime (cefuroxime-axetil), dihydratecephalothin, moxalactam, and loracarbef, wherein said cephalosporin antibiotic is applied directly to affected dermal tissues in an amount effective to treat the acne, wherein said cephalosporin antibiotic is present in an amount in a range of 0.5-5% by weight and is applied in a carrier consisting essentially of:

ethyl alcohol, in a range of 35-50% by weight,

laureth-4, in a range of 0-1% by weight,

isopropyl alcohol, in a range of 0-10% by weight, and

water, in a range of 35-60% by weight.

9. The method described in claim 8 wherein said cephalosporin antibiotic is present in an amount of 2% by weight and is applied in a carrier consisting essentially of:

ethyl alcohol, 41.5% by weight,

laureth-4, 0.5% by weight,

isopropyl alcohol, 6% by weight, and

water, 50% by weight.

10. A method of treating a human being for acne which comprises administering to the human being an amount of a composition consisting essentially of a cephalosporin antibiotic active ingredient, which is cefaclor, and a pharmaceutical carrier, applied directly to affected dermal tissues, effective to treat the acne, wherein said pharmaceutical carrier is a mixture of water and a water-miscible alcohol in amounts ranging from 42.2% to 99.5% of the composition.

11. A method of treating a human being for acne which comprises the steps of:

topically administering to affected dermal areas of the human being an amount of at least one conventionally topically applied anti-acne medication selected from the group consisting of benzoyl peroxide, sulfur, resorcinol, salicylic acid, and tretinoin in conventional doses, and

topically administering to the affected dermal areas a composition which includes an amount of a cephalosporin antibiotic selected from the group consisting of cefaclor, cefadroxil, cefamandole nafate, cefazolin, cefixime, cefmetazole, cefonicid, cefoperazone, ceforanide, cefotanme, cefotaxime, cefotetan, cefoxitin, cefpodoxime proxetil, ceftazidime, ceftizoxime, ceftriaxone, ceftriaxone moxalactam (a 1-oxa-beta-lactam), cefuroxime, cephalexin, cephalosporin C, cephalosporin C sodium salt, cephalothin, cephalothin sodium salt, cephapirin, cephradine, the 1-acetyloxy ethyl ester of cefuroxime (cefuroxime-axetil), dihydratecephalothin, moxalactam, and loracarbef effective to treat the acne, and a pharmaceutical carrier, wherein said pharmaceutical carrier is a mixture of water and a water-miscible alcohol in amounts ranging from 42.2% to 99.5% of the composition.

12. The method described in claim 11 wherein the antibiotic is present in a range of 0.5% to 10% by weight of the composition.

13. A method of treating a human being for acne which comprises the steps of:

topically administering to affected dermal areas of the human being an amount of at least one conventionally topically administered conventional anti-acne medication selected from the group consisting of benzoyl peroxide and tretinoin in conventional doses, and

topically administering to the affected dermal areas an amount of a composition consisting essentially of a cephalosporin antibiotic active ingredient selected from the group consisting of cefaclor, cefadroxil, cefamandole nafate, cefazolin, cefixime, cefmetazole, cefonicid, cefoperazone, ceforanide, cefotanme, cefotaxime, cefotetan, cefoxitin, cefpodoxime proxetil, ceftazidime, ceftizoxime, ceftriaxone, ceftriaxone moxalactam (a 1-oxa-beta-lactam), cefuroxime, cephalexin, cephalosporin C, cephalosporin C sodium salt, cephalothin, cephalothin sodium salt, cephapirin, cephradine, the 1-acetyloxy ethyl ester of cefuroxime (cefuroxime-axetil), dihydratecephalothin, moxalactam, and loracarbef and a pharmaceutical carrier, effective to treat the acne, wherein the antibiotic is present in a range of 0.5% to 10% by weight of the composition, wherein said pharmaceutical carrier is a mixture of water and a water-miscible alcohol in amounts ranging from 42.2% to 99.5% of the composition.

14. The method described in claim 13 wherein the conventional anti-acne medication is benzoyl peroxide which is present in a range spanning 1% to 30% by weight.

Compositions of clindamycin and benzoyl peroxide for acne treatment

2008-01-11T14:54:00.000-08:00

Abstract

Compositions suitable for the treatment of acne by topical application comprise clindamycin and benzoyl peroxide. Kits for preparing the compositions include a solution of clindamycin in a first container and a gel suspension of benzoyl peroxide in a second container. Each component is stored at a pH which promotes stability, and the combination of the two components provides a final composition having a pH which promotes stability and enhances viscosity.

Patent number: 5733886
Filing date: Apr 28, 1994
Issue date: Mar 31, 1998
Inventors: Lloyd J. Baroody, Gordon J. Dow, Debra A. Dow, Robert Lathrop
Assignees: Lloyd J. Baroody, Gordon J. Dow

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What is claimed is:

1. A topical therapeutic gel composition which is stable at room temperature for at least one month comprising a combination of a pharmaceutically acceptable fluid carrier, and as a first active component, benzoyl peroxide in suspension in a gelling agent, and as a second active component, a solution of a pharmaceutical grade of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride, the resulting composition having a concentration of benzoyl peroxide from 1% to 20% by weight, a concentration of clindamycin from 0.2% to 4% by weight, a pH of about 4 to less than 7.0 and a viscosity which is higher than the viscosity of the benzoyl peroxide suspension, and the solution of clindamycin before combination with the first active component having an adjusted pH in the range from about 5.9 to 6.9.

2. A kit for preparing a topical therapeutic gel composition which is stable at room temperature for at least one month after mixture of the components of the composition, said kit comprising:

a first container holding a suspension of benzoyl peroxide in a gelling agent at a pH in the range from about 3.5 to 7.0,

a second container holding an aqueous solution of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride at an adjusted pH in the range from about 5.9 to 6.9 and

instructions associated with the kit to combine the benzoyl peroxide suspension with the clindamycin solution, whereby the resulting composition is a gel having a pH in the range of 4 to less than 7 and having enhanced viscosity in comparison with that of the benzoyl peroxide suspension or the clindamycin solution and the instructions associated with the kit do not call for or require storage of the composition under refrigeration after combination of the benzoyl peroxide suspension and the clindamycin solution.

3. The topical composition of claim 1 wherein the gelling agent is a carboxylated polymer.

4. The topical therapeutic composition of claim 3 wherein the carboxylated polymer is a carboxy vinyl polymer.

5. The topical composition of claim 4 wherein the concentration of the carboxy vinyl polymer in the resulting composition is in the range from 0.1% to 5% by weight.

6. The topical therapeutic composition of claim 4 wherein the pH of the resulting composition is in the range of 4.5 to 5.5.

7. A method for preparing a topical therapeutic gel composition which is stable at room temperature, said method comprising combining (a) an aqueous suspension of benzoyl peroxide initially at a pH of 3.5 to 7.0 in a gelling agent with (b) a stable aqueous solution of a pharmaceutical grade of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride at an adjusted pH in the range from about 5.9 to 6.9 and selected to provide a pH of the composition in the range from 4.5 to below 7, obtaining the resulting therapeutic gel composition which is stable at room temperature for at least one month, and which has a viscosity greater than that of either the benzoyl peroxide suspension or the clindamycin solution.

8. The topical therapeutic composition of claim 1 wherein the resulting composition has a uniform consistency and has a viscosity in the range from 7.times.10.sup.4 cp to 12.times.10.sup.4 cp.

9. The topical therapeutic composition of claim 8 wherein the resulting composition has a viscosity in the range from 8.times.10.sup.4 cp to 10.times.10.sup.4 cp.

10. The topical therapeutic composition of claim 9 which is aqueous.

11. The composition of claim 7 in which after admixing the benzoyl peroxide and the clindamycin 97% of the benzoyl peroxide remains after 3 months when the resulting composition is stored at room temperature.

12. The composition of claim 7 in which after admixing the two components, the pH of the composition is between about 4.03 and about 4.85 and no more than about 20% of the clindamycin is lost after 1 month when the composition is stored at 40.degree. C.

13. The composition of claim 7 wherein the benzoyl peroxide component, prior to combining with the clindamycin component, retains 95% of its original concentration of benzoyl peroxide when the benzoyl peroxide component is stored at 40.degree. C. for 3 months.

14. The composition of claim 7 wherein the clindamycin component, prior to combining with the benzoyl peroxide component, retains 89% of its original concentration of clindamycin when the clindamycin component is stored at 40.degree. C. for 3 months.

15. The kit of claim 2 wherein the gelling agent is a carboxylated polymer.

16. The kit of claim 15 wherein the carboxylated polymer is a carboxy vinyl polymer.

17. A method for treating acne which comprises applying to affected skin areas of a patient a therapeutically effective amount of a gel composition which is stable at room temperature for at least a month, the composition having a pH in the range of about 4 to less than 7, comprising a combination of a pharmaceutically acceptable fluid carrier containing a mixture of a first active component, benzoyl peroxide in suspension in a gelling agent, and as a second active component, a solution of a pharmaceutical grade of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride, the resulting composition having a concentration of benzoyl peroxide from 1% to 20% by weight, a concentration of clindamycin from 0.2% to 4% by weight, a pH of about 4 to less than 7.0 and a viscosity which is higher than the viscosity of the benzoyl peroxide suspension, and the solution of clindamycin before combination with the first active component having an adjusted pH in the range from about 5.9 to 6.9.

18. The kit of claim 16 wherein the pH of the benzoyl peroxide suspension is in the range from 4.0 to 5.0.

19. The kit of claim 2 wherein the amount of benzoyl peroxide suspension in the first container and the amount of clindamycin solution in the second container are selected to provide a pH of the composition in the range from 4.5 to 5.5 and an increased viscosity when the total contents of each container are combined.

20. The kit of claim 19 wherein the benzoyl peroxide suspension has a pH in the range from 4.0 to 5.0, wherein the clindamycin is in a concentration from 2% to 15% by weight and at a pH from 6.0 to 6.5, and wherein the written instructions for use with the kit provide for combining the benzoyl peroxide suspension with the clindamycin solution at a weight ratio selected to provide a stable gel product having a pH in the range from 4.5 to 5.5 and of enhanced viscosity in comparison with that of the benzoyl peroxide suspension and the clindamycin solution.

21. The kit of claim 20 wherein the volume ratio of clindamycin solution to benzoyl peroxide suspension is in the range from 1 to 9 or 2 to 9.

22. The kit of claim 2 wherein the viscosity of the resulting composition is in the range of 7.times.10.sup.4 cp to about 12.times.10.sup.4 cp.

23. The kit of claim 22 wherein the viscosity of the resulting composition is in the range from 8.times.10.sup.4 cp to 10.times.10.sup.4 cp.

24. The kit of claim 23 wherein the amount of benzoyl peroxide suspension is from 2.5 g to 100 g and the amount of clindamycin solution is from 0.5 g to 60 g and the clindamycin is clindamycin phosphate.

25. The kit of claim 2 wherein the viscosity of the benzoyl peroxide in the gelling agent is less than about 9.times.10.sup.4 cp.

26. The topical therapeutic composition of claim 1 wherein the clindamycin is clindamycin phosphate.

27. The topical therapeutic composition of claim 26 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

28. The topical therapeutic composition of claim 27 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

29. The kit of claim 22 wherein the clindamycin is clindamycin phosphate.

30. The kit of claim 29 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

31. The kit of claim 30 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

32. The method of preparation of claim 7 wherein the clindamycin is clindamycin phosphate.

33. The method of preparation of claim 32 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

34. The method of preparation of claim 33 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

35. The method of treatment of claim 17 wherein the clindamycin is clindamycin phosphate.

36. The method of treatment of claim 35 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5

37. The method of treatment of claim 36 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

38. A topical therapeutic gel composition which is stable at room temperature for at least one month comprising a combination of a pharmaceutically acceptable fluid carrier, and as a first active component, benzoyl peroxide in suspension in a gelling agent, and as a second active component, a solution of a pharmaceutical grade of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride, the resulting composition having a concentration of benzoyl peroxide from 1% to 20% by weight, a concentration of clindamycin from 0.2% to 4% by weight, a pH of about 4 to less than 7.0 and a viscosity which is higher than the viscosity of the benzoyl peroxide suspension, the composition being free of dioctyl sodium sulfosuccinate, and the solution of clindamycin before combination with the first active component having an adjusted pH in the range from about 5.9 to 6.9.

39. A kit for preparing a topical therapeutic gel composition which is stable at room temperature for at least one month after mixture of the components of the composition, the composition being free of dioctyl sodium sulfosuccinate, said kit comprising:

a first container holding a suspension of benzoyl peroxide in a gelling agent at a pH in the range from about 3.5 to 7.0,

40. A method for preparing a topical therapeutic gel composition which is stable at room temperature, the composition being free of dioctyl sodium sulfosuccinate, said method comprising combining (a) an aqueous suspension of benzoyl peroxide initially at a pH of 3.5 to 7.0 in a gelling agent with (b) a stable aqueous solution of a pharmaceutical grade of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride at an adjusted pH of about 5.9 to 6.9 and selected to provide a pH of the composition in the range from 4.5 to below 7, obtaining the resulting therapeutic gel composition which is stable at room temperature for at least one month, and which has a viscosity greater than that of either the benzoyl peroxide suspension or the clindamycin solution.

41. A method for treating acne which comprises applying to affected skin areas of a patient a therapeutically effective amount of a gel composition which is stable at room temperature for at least a month, the composition having a pH in the range of about 4 to less than 7 comprising a combination of a pharmaceutically acceptable fluid carrier containing a mixture of a first active component, benzoyl peroxide in suspension in a gelling agent, and as a second active component, a solution of a pharmaceutical grade of a clindamycin selected from the group consisting of clindamycin phosphate and clindamycin hydrochloride at an adjusted pH of about 5.9 to 6.9, the resulting composition having a concentration of benzoyl peroxide from 1% to 20% by weight, a concentration of clindamycin from 0.2% to 4% by weight, and a viscosity which is higher than the viscosity of the benzoyl peroxide suspension, the composition being free of dioctyl sodium sulfosuccinate.

42. The topical therapeutic gel composition of claim 38 wherein the solution of clindamycin before combination with the first active component, has an adjusted pH in the range from about 6.0 to 6.5.

43. The topical therapeutic gel composition of claim 42 wherein the clindamycin is clindamycin phosphate.

44. The topical therapeutic gel composition of claim 43 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

45. The topical therapeutic gel composition of claim 44 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

46. The kit for preparing a topical therapeutic gel composition of claim 39 wherein the solution of clindamycin before combination with the first active component, has an adjusted pH in the range from about 6.0 to 6.5.

47. The kit of claim 46 wherein the clindamycin is clindamycin phosphate.

48. The kit of claim 47 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

49. The kit of claim 48 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

50. The method for preparing a topical therapeutic gel composition of claim 40 wherein the solution of clindamycin before combination with the first active component, has an adjusted pH in the range from about 6.0 to 6.5.

51. The method for preparing a topical therapeutic gel composition of claim 50 wherein the clindamycin is clindamycin phosphate.

52. The method for preparing a topical therapeutic gel composition of claim 51 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

53. The method for preparing a topical therapeutic gel composition of claim 52 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

54. The method for treating acne of claim 41 wherein the solution of clindamycin before combination with the first active component, has an adjusted pH in the range from about 6.0 to 6.5.

55. The method of treating acne of claim 54 wherein the clindamycin is clindamycin phosphate.

56. The method of treating acne of claim 55 wherein the adjusted pH of the clindamycin solution is in the range of about 6.0 to 6.5.

57. The method of treating acne of claim 56 wherein the clindamycin solution is chemically stable for two months, measured by the potency of the clindamycin.

Acne treatment with multifunctional enzyme

2008-01-11T14:23:00.000-08:00

Abstract

The invention relates to a multifunctional enzyme that can be derived from crustaceans or fish. The enzyme has at least one of a chymotrypsin, trypsin, elastase, collagenase and exo peptidase activity, and a molecular weight between about 20 kd and about 40 kd as determined by SDS PAGE. Preferably, the multifunctional enzyme has substantial anti cell-cell adhesion activity. Preferably, the multifunctional enzyme has substantial homology with the krill multifunctional enzyme. These enzymes are useful for treating viral infections such as herpes outbreaks, fungal, bacterial or parasitic infections, including the primary and secondary infections of leprosy, colitis, ulcers, hemorrhoids, corneal scarring, dental plaque, acne, cystic fibrosis, blood clots, wounds, immune disorders including autoimmune disease and cancer. Additionally, the invention relates to a method of purifying the multifunctional enzyme, and to a preparation of essentially purified multifunctional enzyme.

Patent number: 5958406
Filing date: Feb 8, 1996
Issue date: Sep 28, 1999
Inventors: Johan R. de Faire, Richard L. Franklin, John Kay, Ragnvald Lindblom
Assignee: Phairson Medical Inc.
Primary Examiner: Jay Williams

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What is claimed is:

1. A method of treating acne or eczema comprising topically administering an acne or eczema treating effective amount of a krill-derived multifunctional enzyme, wherein the multifunctional enzyme has at least two of a chymotrypsin, trypsin, collagenase, elastase or exo peptidase activity, a molecular weight between about 26 kd and about 32 kd as determined by SDS PAGE, and an N-terminal sequence comprising:

I-V-G-G-X-E-V-T-P-H-A-Y-P-W-Q-V-G-L-F-I-D-D-M-Y-F (SEQ ID NO:20)

wherein X is any amino acid.

2. The method of claim 1, wherein the enzyme has endo and exopeptidase activities.

3. The method of claim 1, wherein the enzyme has at least three of said proteolytic activities.

4. The method of claim 1, wherein the enzyme has at least four of said proteolytic activities.

5. The method of claim 1, wherein the enzyme has all of said proteolytic activities.

6. The method of claim 1, wherein the enzyme removes or inactivates at least one cell surface receptor selected from the group consisting of ICAM-1 (i.e., CD 54), ICAM-2, VCAM-1, CD4, CD8, CD28, CD29D, CD31, CD44, CD 49, CD62L, CD102 and the asialo GM1 ceramide.

7. The method of claim 6, wherein the enzyme removes or inactivates at least one cell surface receptor selected from the group consisting of ICAM-1, CD62L, CD4 and CD8.

Mature protein synthesis

2008-01-10T06:25:00.000-08:00

Abstract

A method is provided for synthesizing within a bacterial host, and secreting through the membrane of the host, a selected mature protein or polypeptide. The method involves:

Patent number: 4338397
Filing date: Apr 11, 1980
Issue date: Jul 6, 1982
Inventors: Walter Gilbert, Karen Talmadge
Assignee: President and Fellows of Harvard College

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What is claimed is:

1. A method of synthesizing within a bacterial host, and secreting through the membrane of the bacterial host, a selected mature protein or polypeptide, which comprises:

(a) cleaving a cloning vehicle, comprising a plasmid, phage DNA or other DNA sequence which is able to replicate in the bacterial host, to form a cleavage site after a promoter of either (1) a bacterial or phage gene within the cloning vehicle or (2) a DNA fragment of the bacterial or phage gene;

(b) forming a hybrid gene by inserting into the cleavage site a non-bacterial DNA fragment which codes for a precursor of the selected protein or polypeptide, including the signal sequence of the selected protein or polypeptide;

(d) culturing the transformed bacterial host to secrete the selected protein or polypeptide.

2. The method of claim 1 wherein the bacterial or phage gene or the DNA fragment thereof codes for a normally secreted protein or polypeptide and the cleavage site is before, within or no more than approximately 60 nucleotides after the translational start signal of the bacterial or phage gene or the DNA fragment thereof.

3. The method of claim 1 wherein the bacterial or phage gene or the DNA fragment thereof codes for a normally non-secreted protein or polypeptide and the cleavage site is before, within or no more than approximately 40 nucleotides after the translational start signal of the bacterial or phage gene or the DNA fragment thereof.

4. The method of claims 2 or 3 wherein the cleavage site is within or no more than approximately 40 nucleotides after the translational start signal of the bacteria or phage gene or the DNA fragment thereof.

5. The method of claim 1 wherein a DNA fragment of the E. coli penicillinase gene is cleaved.

6. The method of claim 5 wherein the cloning vehicle is derived from the plasmid pBR322.

7. The method of claim 1 wherein the non-bacterial DNA fragment codes for preproinsulin, preserum albumin, prehuman growth hormone, preparathyroid hormone, or preinterferon.

8. A cloning vehicle, comprising a plasmid, phage DNA or other DNA sequence which is able to replicate in a bacterial host and comprising in order:

a promoter of a bacterial or phage gene;

a translation start signal; and

a non-bacterial DNA fragment which codes for a precursor of a protein or polypeptide, including the signal sequence of the protein or polypeptide; the reading frame of the non-bacterial DNA fragment being located in the reading frame define by the translational start signal.

9. The cloning vehicle of claim 8 which further includes a ribosome binding site between the promoter and the translational start signal.

10. The cloning vehicle of claim 9 wherein the promoter is the promoter of the E. coli penicillinase gene.

11. The cloning vehicle of claim 9 which further includes no more than approximately 40 nucleotides of the bacterial or phage gene after the translational start signal and before the non-bacterial DNA fragment.

12. The cloning vehicle of claim 9 wherein the non-bacterial DNA fragment codes for preproinsulin, preserum albumin, prehuman growth hormone, preparathyroid hormone, or preinterferon.

13. A bacterial host transformed with a cloning vehicle, the cloning vehicle comprising a plasmid, phage DNA or other DNA sequence which is able to replicate in the bacterial host and comprising in order:

a promoter of a bacterial or phage gene;

a translational start signal; and

14. The host of claim 13 which further includes a ribosome binding site between the promoter and the translational start signal.

15. The host of claim 14 wherein the non-bacterial DNA fragment codes for preproinsulin, preserum albumin, prehuman growth hormone, preparathyroid hormone, or preinterferon.

16. A method of synthesizing within a bacterial host, and secreting through the membrane of the bacterial host, a selected mature protein or polypeptide, which comprises culturing the bacterial host; the bacterial host being transformed with a cloning vehicle, comprising a plasmid, phage DNA or other DNA sequence which is able to replicate in the bacterial host and comprising in order:

a promoter of a bacterial or phage gene;

a translational start signal; and

a non-bacterial DNA fragment which codes for a precursor of the selected protein or polypeptide, including the signal sequence of the selected protein or polypeptide; the reading frame of the non-bacterial DNA fragment being located in the reading frame defined by the translational start signal.

17. The method of claim 16 wherein the cloning vehicle further includes a ribosome binding site between the promoter and the translational start signal.

18. The method of claim 17 wherein the promoter is the promoter of the E. coli penicillinase gene.

19. The method of claim 17 wherein the cloning vehicle further includes no more than approximately 40 nucleotides of the bacterial or phage gene after the translational start signal and before the non-bacterial DNA fragment.

Bacillus thuringiensis crystal protein in Escherichia coli

2008-01-10T06:22:00.000-08:00

Abstract

Expression of the crystal protein of Bacillus thuringiensis in Escherichia coli is described by use of plasmids containing heterologous DNA coding for the crystal protein. Genetically engineered bacterial host strains transformed by the plasmids of the invention express Bacillus thuringiensis crystal proteins without exhibiting the growth phase limitations characteristic of the natural bacterial host species.

Patent number: 4467036
Filing date: Mar 30, 1982
Issue date: Aug 21, 1984
Inventors: H. Ernest Schnepf, Helen R. Whiteley
Assignee: The Board of Regents of the University of Washington
Primary Examiner: James Martinell

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What is claimed is:

1. A hybrid recombinant plasmid capable of replication in an Escherichia coli bacterial host species, said plasmid containing expressible heterologous DNA coding for a polypeptide which has the immunological properties of the crystal protein of Bacillus thuringiensis, said plasmid further containing expressible heterologous DNA having a DNA portion derived from plasmids of Bacillus thuringiensis having a molecular mass greater than 10.times.10.sup.6 M.sub.r, said Bacillus thuringiensis derived DNA portion being identifiable with a Pvu II-C DNA fragment probe, said hybrid recombinant plasmid further comprising an expression mechanism for said expressible heterologous DNA which is recognized by the host species' system.

2. A hybrid recombinant plasmid capable of replication in an Escherichia coli bacterial host species, said plasmid containing expressible heterologous DNA coding for a polypeptide which has the immunological properties of the crystal protein of Bacillus thuringiensis, said plasmid further containing expressible heterologous DNA having a DNA portion derived from plasmids of Bacillus thuringiensis having a molecular mass greater than 10.times.10.sup.6 M.sub.r, said Bacillus thuringiensis derived DNA portion further being identifiable with a Pvu II-C DNA fragment probe, said Bacillus thuringiensis derived DNA portion further being selected from the group consisting of Bacillus thuringiensis subspecies tolworthi; Bacillus thuringiensis subspecies darmstadiesis; Bacillus thuringiensis subspecies sotto; Bacillus thuringiensis subspecies thuringiensis; Bacillus thuringiensis subspecies thuringiensis, strain HD-290; Bacillus thuringiensis subspecies thuringiensis, strain HD-120; Bacillus thuringiensis subspecies thuringiensis, strain HD-2; Bacillus thuringiensis subspecies kurstaki, strain HD-244; Bacillus thuringiensis subspecies kurstaki, strain HD-73; Bacillus thuringiensis subspecies kurstaki, strain HD-1; Bacillus thuringiensis subspecies alesti, strain HD-4; Bacillus thuringiensis subspecies toumanoffi, strain F-9; Bacillus thuringiensis subspecies galleriae, strain HD-8; Bacillus thuringiensis subspecies wuhnanesis, strain F-6 and Bacillus thuringiensis subspecies morrisoni, strain F-5; said hybrid recombinant plasmid further including an expression mechanism for said heterologous DNA which is recognized by the host species' system.

3. Hybrid recombinant plasmids having the Bacillus thuringiensis crystal protein coding characteristics of plasmids: pES1, as carried in Escherichia coli strain ES12, (ATCC Number 31995); pJWK20, as carried in Escherichia coli strain JWKI (ATCC Number 31997); and pJWK18, as carried in Escherichia coli strain JWKII, (ATCC Number 31998), and their progeny resulting from normal cell division of the parental bacterial cells or plasmids.

Immunogenic polysaccharide-protein conjugates

2008-01-10T04:54:00.000-08:00

Abstract

Antigenic polysaccharides are modified to generate a terminally-located aldehyde group by controlled oxidation of vicinal hydroxyl groups, e.g. of unlinked terminal non-reducing sialic acid residues. In some cases where there is a reducing end group, e.g. of the type N-acetylmannosamine residue, it can be made into the most susceptible site for oxidation by initially reducing it to its open chain hydroxyl form, e.g. N-acetylmannosaminitol. The vicinal hydroxyl oxidation is controlled to yield a reactive aldehyde group which is then covalently linked to a free amino group of a selected protein by reductive amination. The resulting polysaccharide-protein conjugates are soluble and have been found to have enhanced antigenicity compared to the polysaccharide alone. This terminal aldehyde:free amine group reductive amination can be applied to various polysaccharide antigens and various well-tolerated proteins, preferably protein immunogens. For example, meningococcal group A, B and...

Patent number: 4356170
Filing date: May 27, 1981
Issue date: Oct 26, 1982
Inventors: Harold J. Jennings, Czeslaw Lugowski
Assignee: Canadian Patents & Development Ltd.

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What is claimed is:

1. A method of preparing antigenic polysaccharide: protein conjugates, comprising:

(a) providing an antigenic polysaccharide which has reactive vicinal hydroxyl groups in a terminal portion of the molecule and has a MW above about 2000;

(b) subjecting said vicinal hydroxyl groups at a terminal location to controlled oxidation only sufficient to generate a terminal reactive aldehyde group therefrom on the polysaccharide;

(c) selecting a physiologically-tolerated protein having a free amino group and reacting said amino group with said aldehyde group by reductive amination, to covalently link said polysaccharide and protein; and

(d) recovering a substantially non-crosslinked, soluble, antigenic polysaccharide:protein conjugate.

2. The method of claim 1 wherein the antigenic polysaccharide is selected from the group derived from meningococci, Haemophilus influenza, pneumococci, .beta.-hemolytic streptococci, and E. coli.

3. The method of claim 1 wherein the protein is selected from the group consisting of tetanus toxoid, diphtheria toxoid, and immunogenic proteins derived from bacteria selected from .beta.-hemolytic streptococci, Haemophilus influenza, meningococci, pneumococci, and E. coli.

4. The method of claim 1 wherein the polysaccharide initially has no terminal vicinal hydroxyl groups but has a terminal reducing sugar residue which is reduced to form reactive vicinal hydroxyl groups in (a).

5. The method of claim 4 wherein the sugar residue is N-acetylmannosamine residue.

6. The method of claim 4 wherein the reduction is effected using sodium borohydride at a pH of about 7.5-10.

7. The method of claim 6 wherein the pH is about 8-9.

8. The method of claim 1 wherein the controlled oxidation in (b) is effected using periodate reagent for a limited time.

9. The method of claim 8 wherein the polysaccharide is derived from meningococci, and the time for controlled oxidation is within 10-15 minutes.

10. The method of claim 1 wherein meningococcal group A, B or C polysaccharides having terminal vicinal hydroxyl groups are utilized and are oxidized sufficiently to convert only the terminal vicinal hydroxyl groups to a terminal aldehyde group, reductive amination carried out to link covalently the terminal aldehyde group to an amino group on the selected protein tetanus toxoid molecule, and recovering a soluble conjugate thereof of enhanced antigenicity.

11. An antigenic-polysaccharide:protein conjugate wherein the polysaccharide and protein are covalently linked through a ##STR3## linkage to a terminal portion of the polysaccharide without significant cross-linking, said antigenic polysaccharide having a MW above about 2000.

12. The conjugate of claim 11 wherein the antigenic polysaccharide is selected from the group derived from meningococci, Haemophilus influenza, pneumococci, .beta.-hemolytic streptococci, and E. coli.

13. The conjugate of claim 11 wherein the protein is selected from the group consisting of tetanus toxoid, diphtheria toxoid, and immunogenic proteins derived from bacteria selected from .beta.-hemolytic streptococci, Haemophilus influenza, meningococci, pneumococci and E. coli.

14. The conjugate of claim 11 wherein the antigenic polysaccharide is selected from meningococcal Group A, B or C polysaccharides and the protein is tetanus toxoid.

15. The conjugate of claim 11 wherein the antigenic polysaccharide is derived from Haemophilus influenza and the protein is tetanus toxoid.

16. The conjugate of claim 11 wherein said linkage is through an end-group terminal reducing sugar moiety on the polysaccharide.

17. The conjugate of claim 16 wherein said reducing sugar moiety is N-acetylmannosaminitol.

18. The conjugate of claim 11 wherein said linkage is through a lysine amino group on the protein.

19. The conjugate of claim 11 wherein the polysaccharide and protein are derived from the same bacteria.

20. A method of immunizing against infection susceptible humans or animals comprising, administering a vaccine comprising the conjugate of claim 11 in an immunogenic amount by intramuscular or subcutaneous injection.

21. The method of claim 20 wherein the dosage of the conjugate is equivalent to from about 5 to about 25 micrograms for the human infant.

22. The method of claim 21 wherein human infants are immunized with a vaccine comprising at least one of (a) the conjugate of meningococcal polysaccharide, and (b) the conjugate of H. influenza polysaccharide.

23. A vaccine comprising at least one conjugate as defined in claim 11.

24. A vaccine for infants comprising the conjugate of claim 11 wherein the initial non-conjugated polysaccharide is of the type for which the immune response is non-thymus-controlled.

25. A human infant vaccine comprising the conjugate of claim 11 wherein the polysaccharide comprises at least one of meningococcal polysaccharide and Haemophilus influenza polysaccharide.

26. A vaccine as in claim 24 in a dosage unit form wherein the conjugate is present in the equivalent of from about 5 to about 25 micrograms based on the human infant.

Uses of green-fluorescent protein

2008-01-10T04:52:00.000-08:00

Abstract

This invention provides a cell comprising a DNA molecule having a regulatory element from a gene, other than a gene encoding a green-fluorescent protein operatively linked to a DNA sequence encoding the green-fluorescent protein. This invention also provides a method for selecting cells expressing a protein of interest which comprises: a. introducing into the cells a DNAI molecule having DNA sequence encoding the protein of interest and DNAII molecule having DNA sequence encoding a green-fluorescent protein; b. culturing the introduced cells in conditions permitting expression of the green-fluorescent protein and the protein of interest; and c. selecting the cultured cells which express green-fluorescent protein, thereby selecting cells expressing the protein of interest. Finally, this invention provides various uses of a green-fluorescent protein.

Patent number: 5491084
Filing date: Sep 10, 1993
Issue date: Feb 13, 1996
Inventors: Martin Chalfie, Douglas Prasher
Assignees: The Trustees of Columbia University in the City of New York, Woods Hole Oceanographic Institution

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What is claimed is:

1. A host cell comprising a DNA molecule having a regulatory element from a gene, other than a gene encoding an Aequorea victoria green-fluorescent protein operatively linked to a DNA sequence encoding the fluorescent Aequorea victoria green-fluorescent protein.

2. A cell of claim 1, wherein the cell is selected from a group consisting of bacterial cell, yeast cell, fungal cell, plant cell or animal cell.

3. A cell of claim 1, wherein the regulatory element is a promoter.

4. A cell of claim 3, wherein the promoter is activated by a heavy metal.

5. A cell of claim 3, wherein the promoter is a P450 promoter.

6. A cell of claim 3, wherein the promoter is from a gene encoding a stress protein.

7. A cell of claim 6, wherein the stress protein is a heat-shock protein.

8. A cell of claim 1, wherein the regulatory element is an enhancer.

9. A method for selecting cells expressing a protein of interest which comprises:

(a) introducing into the cells a DNAI molecule having DNA sequence encoding the protein of interest and DNAII molecule having DNA sequence encoding an Aequorea victoria green-fluorescent protein;

(b) culturing the introduced cells in conditions permitting expression of the Aequorea victoria green-fluorescent protein and the protein of interest; and

(c) selecting the cultured cells which express Aequorea victoria green-fluorescent protein, thereby selecting cells expressing the protein of interest,

wherein DNAI and DNAII are linked.

10. A method for selecting cells expressing a protein of interest which comprises:

(a) introducing into the cells a DNAI molecule having DNA sequence encoding the protein of interest and DNAII molecule having DNA sequence encoding an Aequorea victoria green-fluorescent protein;

(b) culturing the introduced cells in conditions permitting expression of the Aequorea victoria green-fluorescent protein and the protein of interest; and

(c) selecting the cultured cells which express Aequorea victoria green-fluorescent protein, thereby selecting cells expressing the protein of interest,

wherein the cells are selected from a group consisting of yeast cells, fungal cells, insect cells, nematode cells, plant or animal cells.

11. A method for localizing a protein of interest in a cell which comprises:

(a) introducing into a cell a DNA molecule having DNA sequence encoding the protein of interest linked to DNA sequence encoding an Aequorea victoria green-fluorescent protein such that the protein produced by the DNA molecule will have the protein of interest fused to the Aequorea victoria green-fluorescent protein;

(b) culturing the cell in condition permitting expression of the fused protein; and

(c) detecting the location of the fluorescence of the fused protein in the cell, thereby localizing a protein of interest in a cell.

12. A method of claim 11, wherein the cell normally expresses the protein of interest.

Manufacturing protein microspheres

2008-01-10T04:50:00.000-08:00

Abstract

Processes for producing biocompatible and biodegradable protein microspheres with controlled porosity and microsphere sizes are disclosed. Generally, the processes are accomplished as follows: (a) dissolving a source of protein in a mildly acidic or basic aqueous medium, in the presence or absence of a biomodifying agent, (b) adding a cross-linking reagent to the dissolved protein molecules in an amount effective subsequently to cross-link the protein molecules without gelation; (c) adding a water soluble surfactant to modify the surface of the partially cross-linked protein molecules, (d) adding a water soluble organic desolubilizer to desolubilize the protein molecules to allow cross-linkage of nearby protein molecules into water-insoluble microspheres. Alternatively, the cross-linking step of (b) is employed after desolvation of the microspheres. Incorporation of the biomodifying agent, if any, can be achieved by prior bonding to the protein molecules, addition during the...

Patent number: 5069936
Filing date: Aug 7, 1989
Issue date: Dec 3, 1991
Inventor: Richard C. K. Yen

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What is claimed is:

1. A process for manufacturing protein microspheres, comprising:

a) dissolving protein molecules in an aqueous buffer solution to form a protein solution;

b) adding a surfactant;

c) adding a desolvating agent to the admixture of protein solution and surfactant to produce a turbid mixture comprising substantially monodispersed protein microspheres; and

d) adding a cross-linking agent to the turbid mixture formed in step c).

2. The process described in claim 1 wherein said protein molecules have at least one biological element attached thereto.

3. The process described in claim 1 additionally comprising adding at least one biological element to said protein solution prior to adding said desolvating agent.

4. The process described in claim 1 additionally comprising adding at least one biological element to said turbid mixture prior to adding said cross-linking agent and resulting in attachment of biological element to said protein microspheres.

5. The process described in claim 1 additionally comprising adding at least one biological element subsequent to the addition of said cross-linking agent and resulting in attachment of biological element to said protein microspheres.

6. The process described in claims 2, 3, 4 or 5 wherein the biological element is chosen from the group consisting of the following: alkaloids, amino acids, antibiotics, carbohydrates, carcinogens, immunoglobulins or globulins, halogenated compounds, hormones, lipids, nucleotides, polypeptides, porphyrins, steroids, vitamins, lecithins, metal sulfides, metal halides, metal oxides, antifungal compounds, enzymes, and chemotherapeutic agents.

7. The process described in claim 1 wherein said protein molecules are chosen from any one or more of the group consisting of albumin, collagen, hemoglobin, and immunoglobulin.

8. The process described in claim 7 wherein the concentration of protein molecules just prior to the addition of desolvating agent is within the range of approximately 0.225-62.50 mg/ml.

9. The process described in claim 7 wherein said protein molecules comprise albumin.

10. The process described in claim 9 wherein the concentration of albumin just prior to the addition of desolvating agent is within the range of approximately 9.00-20.00 mg/ml.

11. The process described in claim 10 wherein the concentration of albumin just prior to the addition of desolvating agent is 15 mg/ml within an accuracy of plus or minus 10%.

12. The process described in claim 7 wherein said protein molecules are hemoglobin.

13. The process described in claim 12 wherein the concentration of hemoglobin just prior to the addition of desolvating agent is 3.7 mg/ml within an accuracy of plus or minus 20%.

14. The process described in claim 1 wherein said aqueous buffer solution is maintained between 0 and 42 degrees Centigrade.

15. The process described in claim 1 wherein the pH of said aqueous buffer solution is maintained between 5 and 9.

16. The process described in claim 1 wherein the concentration of said surfactant is approximately 0.1 to 50 mg/ml of said aqueous buffer solution.

17. The process described in claim 11 wherein said surfactant is a detergent.

18. The process described in claim 1 wherein said surfactant is sodium lauryl sulfate.

19. The process described in claim 1 wherein said desolvating agent is an alcohol.

20. The process described in claim 19 wherein said alcohol is chosen from the group consisting of methanol, ethanol, propanol, and butanol.

21. The process described in claim 11 wherein said cross-linking agent is a polyaldehyde which is added in an amount in the range of 0.002 to 10.0 volume per 100 volume of said aqueous buffer solution.

22. The process described in claim 21 wherein polyaldehyde is selected from the group consisting of glutaraldehyde, polyglutaraldehyde, and polyacrotein.

23. The process described in claim 1 additionally comprising the step of removing said desolvating agent and other unreacted or partially-reacted soluble material from said protein microspheres.

24. The process described in claim 23 wherein said step of removing desolvating agent is chosen from one or more of the following methods: dialysis, centrifugation and washing, gradient centrifugation, gel-filtration, electrophoresis, column chromatography, gradient centrifugation, thin-layer chromatography, hollow-fiber ultrafiltration, and tangential filtration.

Fluid infusion sleeve for use during eye surgery

2008-01-10T04:48:00.000-08:00

Abstract

A surgical instrument for removing a cataract from a patient's eye including a hollow vibratable needle surrounded by a hollow infusion sleeve which conforms to the surgical incision and thereby prevents leakage from the incision, and also with means preventing the hollow infusion sleeve from collapsing against the hollow vibratable needle. A second embodiment including a hollow vibratable needle surrounded by two hollow infusion sleeves with conformity of the outer sleeve to the incision and means for preventing the infusion sleeve from collapsing against the hollow vibratable needle.

Patent number: 5084009
Filing date: Apr 18, 1990
Issue date: Jan 28, 1992
Inventor: Richard J. Mackool
Primary Examiner: Steven J. Shumaker

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What is claimed is:

1. A surgical instrument for removing a cataract through an incision in a patient's eye, comprising a hollow, compressible infusion sleeve; said hollow, compressible infusion sleeve including a tapered, ported distal end portion designed to be located within a patient's eye during cataract removal and having an extreme end portion; said hollow, compressible, infusion sleeve further including a second cylindrical portion configured and designed to extend into a patient's eye; said second cylindrical portion intersecting with and extending away from said tapered, ported distal end portion; a hollow vibratable needle which extends into a patient's eye during the removal of a cataract; said hollow, compressible infusion sleeve second cylindrical portion and said tapered, ported distal end portion surrounding said hollow, vibratable needle with there being a space between the extreme end portion of said tapered, ported distal end portion and the hollow, vibratable needle; a rigid, hollow, non-compressible sleeve surrounding a portion of said hollow, vibratable needle with said rigid, hollow, non-compressible sleeve having a larger diameter than said hollow, vibratable needle, thereby defining a path of fluid between said hollow, vibratable needle and said rigid, hollow, non-compressible sleeve; said rigid, hollow, non-compressible sleeve being surrounded by said hollow, compressible infusion sleeve second cylindrical portion and a portion of said tapered, ported distal end portion of said hollow, compressible infusion sleeve, whereby said rigid, hollow, non-compressible sleeve prevents the hollow, compressible infusion sleeve from collapsing against said hollow, vibratable needle.

2. A surgical instrument for removing a cataract according to claim 1, wherein said rigid, hollow, non-compressible sleeve includes radial ports.

3. A surgical instrument for removing a cataract according to claim 1, wherein said compressible infusion sleeve distal end portion includes discharge port means for directing fluid at an angle with respect to the axis of the hollow, vibratable needle and away therefrom.

Apparatus and method for performing eye surgery

2008-01-10T04:26:00.001-08:00

Abstract

An optical probe configured for insertion into the anterior chamber of an eye, adjacent to the cataractous lens of the eye, comprises an optical source, and an optical waveguide connected to deliver optical radiation from the source to the probe. The optical radiation is in the form of pulses which have a repetition rate, a wavelength and an optical energy selected to cause significant ablation-induced damage to the lens within an ablation zone, and significant acoustic-induced damage to the lens within an acoustic zone, such that the acoustic zone is significantly larger in size than the ablation zone. The acoustic zone is created by generating shock waves which radiate from the ablation zone and propagate through hard nuclear material of the cataractous lens, such that the nuclear material is microfractured. The microfractured lens material is significantly more reactive to the laser pulses than prior to microfracturing,...

Patent number: 5738677
Filing date: May 31, 1995
Issue date: Apr 14, 1998
Inventors: Michael Colvard, Varouj D. Amirkhanian, HeeJung Koh Wescoat, Judy E. Mazza, Colette Cozean
Assignee: Premier Laser Systems, Inc.

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What is claimed is:

1. A method of removing a lens of an eye, comprising:

(a) inserting a probe into the anterior chamber of said eye;

(b) directing pulses of laser radiation from said probe against a location on nuclear material of said lens;

(c) selecting the wavelength, repetition rate and pulse energy of said laser radiation such that during step (b), said pulses simultaneously (1) ablate said lens within an ablation zone, and (2) generate shock waves which radiate from said location and propagate through said nuclear material so as to cause substantial acoustic damage thereto, said damage being in an acoustic zone that extends outside said ablation zone into at least a substantial portion of said nuclear material;

(d) moving said probe such that said pulses of laser radiation are directed onto acoustically damaged nuclear material, whereby said simultaneous ablation and shock wave generation readily transform said nuclear material into an emulsion capable of aspiration; and

(e) aspirating said emulsion from said eye.

2. The method of claim 1, wherein step (b) comprises the step of focusing said lens radiation at a focal spot within said nuclear material of said lens, and wherein step (b) comprises the step of moving said focal spot along a path within said nuclear material sufficiently slowly to cause ablation at multiple locations along said path.

3. The method of claim 2, wherein said focal spot is no more than a few hundred microns in diameter, and wherein step (b) comprises moving said focal spot across substantially the entire lens.

4. The method of claim 1, wherein said wavelength is in a mid-infrared wavelength region and on the order of 3 microns, and wherein said pulse energy is 10-80 mJ per pulse.

5. The method of claim 1, wherein step (b) comprises ablating a crater in said lens.

6. The method of claim 5, wherein said crater is in said nuclear material.

Method utilizing a laser for eye surgery

2008-01-10T03:59:00.000-08:00

Abstract

Surgical apparatus including laser, probe apparatus defining a radiation inlet and a radiation outlet, the radiation inlet being coupled in radiation receiving relationship to the laser, and apparatus for injecting a precisely controllable volume of air adjacent the radiation outlet.

Patent number: 4559942
Filing date: Feb 29, 1984
Issue date: Dec 24, 1985
Inventor: William Eisenberg
Primary Examiner: Ruth S. Smith

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What is claimed is:

1. A method for eye surgery on target tissue in the eye including the steps of coupling a laser to a surgical probe apparatus defining a radiation inlet and a radiation outlet, moving the probe apparatus adjacent to the target tissue in the eye, injecting a precisely controllable volume of air between the radiation outlet and the target tissue, and providing laser radiation from the laser through the probe apparatus to the target tissue while maintaining the volume of air between the probe apparatus and the target tissue, thereby to prevent physical contact between the radiation outlet and the target tissue during laser irradiation.

2. A surgical method according to claim 1 and operative for cataract emulsification and wherein said step of providing laser radiation comprises the steps of irradiating the cataract with a pulse of radiation from a laser, removing the cataract debris created thereby, and repeating the steps of irradiating and removing until the cataract is removed.

3. A method of cataract emulsification according to claim 2 and wherein said step of irradiating the cataract with a pulse of radiation from a laser includes irradiating from a laser selected from the group including a Neodymium YAG, carbon dioxide and Erbium YLF laser.

4. A method according to claim 2 and wherein said step of providing laser radiation comprises the step of irradiating the cataract with a pulse of radiation from an Erbium YLF laser.

Dental restorative cement pastes

2008-01-09T16:22:00.000-08:00

Abstract

Compositions that are useful and unique as dental remineralizers and dental cements, as well as methods for their use, are disclosed. The compositions are mixtures of at least two sparingly soluble calcium phosphates that are present in excess and a dilute aqueous solution approximately saturated with

Patent number: RE33221
Filing date: May 18, 1987
Issue date: May 22, 1990
Inventors: Walter E. Brown, Laurence C. Chow
Assignee: American Dental Association Health Foundation
Primary Examiner: Linda D. Skaling

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What is claimed is:

1. A .[.dental restorative.]. paste .Iadd.consisting essentially of .Iaddend..[.comprising.]. an aqueous mixture of Ca.sub.4 (PO.sub.4)O and at least one other calcium phosphate selected from the group consisting of CaHPO.sub.4.2H.sub.2 O .[.,.]. .Iadd.and .Iaddend.CaHPO.sub.4, .[.Ca.sub.8 H.sub.2 (PO.sub.4).sub.6.5H.sub.2 O, .beta.-Ca.sub.3 (PO.sub.4).sub.2, .beta.-Ca.sub.3 (PO.sub.4).sub.2, and modified Ca.sub.3 (PO.sub.4).sub.2, the paste being capable of hardening.]. .Iadd.which aqueous mixture hardens .Iaddend.into a cement .Iadd.at an ambient temperature.

2. The paste of claim 1 wherein the other calcium phosphate is CaHPO.sub.4.2H.sub.2 O.

3. The paste of claim 1 wherein the other calcium phosphate is CaHPO.sub.4. .[.4. The paste of claim 1 wherein the other calcium phosphate is Ca.sub.8 H.sub.2 (PO.sub.4).sub.6.5H.sub.2 O..]. .[.5. The paste of claim 1 wherein

the other calcium phosphate is .beta.-Ca.sub.3 (PO.sub.4).sub.2..]. 6. The paste of claim 1 wherein both calcium phosphates are in crystalline,

cryptocrystalline, or amorphous form. 7. The paste of claim 1 further .[.comprising.]. .Iadd.including .Iaddend.up to approximately 10% by weight of additional calcium or phosphate containing compounds .Iadd.in an

amount sufficient to alter the pH of the paste.Iaddend.. 8. The paste of claim 7 wherein the additional calcium containing compounds .[.comprise.]. .Iadd.are selected from the group consisting of .Iaddend.CaCl.sub.2

.[.or.]. .Iadd.and .Iaddend.Ca(C.sub.2 H.sub.3 O.sub.2).sub.2. 9. The paste of claim 7 wherein the additional phosphate containing compounds .[.comprise.]. .Iadd.are selected from the group consisting of .Iaddend.NaH.sub.2 PO.sub.4 .[.or.]. .Iadd.and .Iaddend.(NH.sub.4)H.sub.2

PO.sub.4. 10. The paste of claim 1 further .[.comprising.]. .Iadd.including .Iaddend.fluoride containing compounds such that the fluoride content of the paste is up to approximately 3.8% by weight .Iadd.in an amount sufficient to increase the rate of precipitation of

hydroxyapatite from the paste.Iaddend.. 11. The paste of claim 10 wherein the fluoride containing compounds .[.comprise.]. .Iadd.are selected from the group consisting of .Iaddend.CaF.sub.2, SrF.sub.2, NaF, Na.sub.2

SiF.sub.6 .[.or.]. .Iadd.and .Iaddend.NaPO.sub.3 F. 12. A paste .[.comprising.]. .Iadd.consisting essentially of .Iaddend.CaHPO.sub.4 and Ca.sub.4 (PO.sub.4).sub.2 O having a particle size of approximately 1 .mu.m and a 20mM solution of H.sub.3 PO.sub.4 .Iadd., the paste hardening

into a cement at an ambient temperature.Iaddend.. 13. The paste of claim 1 additionally .[.comprising.]. .Iadd.including .Iaddend.a seed crystal compound selected from the group consisting of hydroxyapatite and fluorapatite .Iadd.in an amount sufficient to reduce the setting time of the cement.Iaddend.. .Iadd.14. The paste of claim 13 wherein the seed crystal compound is hydroxyapatite, the hydroxyapatite being present in an amount up to 43% by weight and in an amount sufficient to reduce the setting time of the cement. .Iaddend. .Iadd.15. The paste of claim 1 additionally including up to approximately 5% by weight of a high molecular weight crystal growth inhibitor selected from the group consisting of proteoglycans, glycoproteins, polylysine and protamine in an amount sufficient to inhibit the growth of hydroxyapatite crystals. .Iaddend. .Iadd.16. The paste of claim 1 additionally including .beta.-Ca.sub.3 (PO.sub.4).sub.2 in an amount sufficient to achieve setting expansion of the cement. .Iaddend. .Iadd.17. The paste of claim 1 additionally including up to 1% by weight of a crystal habit modifier selected from the group consisting of Mg.sup.2+, Sr.sup.2+, citrate, phosphonates, carbonate, polyphosphates, sucrose phosphate, and phosphocitrate in an amount sufficient to achieve setting expansion of the

cement. .Iaddend. .Iadd.18. The paste of claim 1 wherein the paste is slightly acidic. .Iaddend. .Iadd.19. The paste of claim 1 where in the

paste is slightly basic. .Iaddend. .Iadd.20. The paste of claim 1 additionally including granular sugar, the sugar being present in an amount up to 20% by weight and in an amount sufficient to form a porous cement upon removal of the sugar by application of hot water to the cement. .Iaddend.

Dental impression supply kit

2008-01-09T16:15:00.000-08:00

Abstract

A dental impression kit to assist the dentist or a dental technician in the making of dental impressions preparatory to the formation of a mold and the manufacture of a crown or full or partial dentures. The kit contains a compact and orderly arranged array of items necessary or desirable in formation of dental impression. Such items include a selection of upper and lower dental impression trays, dental impression material base and catalyst, adhesive, polish, instructions and a mixing pad. From the kit, the dentist is able to select the appropriate type and size of impression tray, mix the impression base and material on a mixing pad, prepare the tray with the adhesive and then fill it with the impression material and take the dental impression, all the while having instructions at hand if necessary. The finished dentures can be polished using the polish kit. Secondary inventory control cases complement the primary case by making inventory available as items from the primary...

Patent number: 4763791
Filing date: Nov 3, 1987
Issue date: Aug 16, 1988
Inventors: George E. Halverson, Gerald A. Nelson
Assignee: Excel Dental Studios, Inc.
Primary Examiner: Bryon Gehman

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What is claimed is:

1. A dental impression supply kit comprising:

a primary case having a base and a cover, said cover movable into and out of covering relationship to the base;

a support member located in and substantially filling the base and having an accessible upper surface when the cover is in position out of covering relationship to the base;

a first plurality of items appropriate to procedures for forming dental impressions;

said support member having a corresponding plurality of upwardly open pockets for holding said first plurality of items, each pocket being individually shaped generally in conformance with the shape of an item to be held;

said first plurality of items including one each of a small size, a medium size, and large size disposable upper dental impression trays;

said pockets including a first row of three pockets having a first shape in conformance with the shape of an upper dental impression tray;

said upper dentral impression trays being located in said first row of pockets;

a first secondary case having a base and a cover movable into and out of covering relationship to the base, a support member located in and substantially filling the base, a plurality of upwardly open pockets having said first shape located in the support member, a plurality of disposable upper dental impression trays of small, medium and large sizes located in said pockets for replenishment of upper dental impression trays depleted from the primary case;

said first plurality of items also including one each of a small size, a medium size and large size lower disposable dental impression trays;

said pockets including a second row of three pockets having a second shape in conformance with the shape of a lower dental impression tray;

said lower dental impression trays being located in said second row of pockets;

a second secondary case having a base and a cover movable into and out of covering relationship to the base, a support member located in and substantially filling the base, a plurality of upwardly open pockets having said second shape located in the support member, a plurality of disposable lower dental impression trays of small, medium and large sizes located in said pockets for replacement of lower dental impression trays from the primary case;

others of said items being located in corresponding pockets of the support member of the primary case and including a depletable container of impression material base, a depletable container of impression material catalyst, and a depletable container of adhesive material for forming a dental impression using one of the upper dental impression trays and one of the lower dental impression trays from the primary case.

2. The dental impression kit of claim 1 wherein: said primary case cover is hingedly connected to the primary case base and has an interior surface carrying holding means for holding a second plurality of items appropriate to dental impression procedures, said second plurality of items including an instruction sheet and a mixing pad.

3. The dental impression kit of claim 2 including: a second instruction sheet fixed to the inner surface of the cover providing directions for use of the dental kit.

4. The dental empressions kit of claim 3 wherein: said first plurality of items includes a dental polish kit.

5. The dental impression kit of claim 1 including: a third secondary case, said third secondary case carrying a plurality of replacement containers of dental impression base, a plurality of replacement containers of dental impression catalyst, and at least one replacement container of adhesive for replacement of corresponding items from the primary case.

6. The dental impression kit of claim 5 wherein: said lower impression dental trays are the type having a generally V-shape with an interior wall spaced from an exterior wall by a bottom wall forming a channel for filling with impression material, and a handle extended from the exterior wall.

7. The dental impression kit of claim 6 wherein: said upper impression trays are of the type having an outer wall, a curved inner platform corresponding to the roof of a mouth, and a bottom wall connecting the curved platform and the outer wall forming a channel to be filled with dental impression material, said channel being generally shaped according to the upper dentures of a person, and a handle extended forwardly from the outer wall.

8. The dental impression kit of claim 7 wherein: said base of the primary case is comprised as a box-like housing with an open top, said first selection of dental impression trays comprising first, second and third trays of small, medium and large size arranged in a row proximate one edge of said base, said second selection of dental impression trays comprising first, second and third dental trays of small, medium and large size arranged proximate an opposite edge of said base, said remainder of the first plurality of items being located between the first and second selections of dental trays.

9. The dental impression kit of claim 8 including: latch means to latch the cover with respect to the base when in covering relationship to the base.

10. A dental impression supply kit comprising:

a primary case having a generally rectangular upwardly open base with perpendicularly orientated side walls and a bottom wall connected to the side walls;

a cover for said base having perpendicularly orientated side walls generally corresponding in shape to the side walls of the base, and a top wall connected to the side walls, said cover having a first side wall hingedly connected to a first side wall of the base for movement between positions in and out of covering relationship to the base;

a first plurality of items appropriate to procedures for forming dental impressions;

support means in the base having a corresponding plurality of upwardly open pockets for holding said first plurality of items, each pocket being individually shaped genreally in conformance with the shape of an item to be held;

said plurality of open pockets including a first row of three pockets proximate an edge of a second side wall of a box perpendicular to the first side wall, said pockets each having the shape of a lower dental impression tray, and a second row of three pockets disposed proximate an edge of a third side wall of the box perpendicular to the first side wall and having the shape of an upper dental impression tray;

said items including small, medium and large disposable lower dental impression trays located in said first row of pockets, small, medium and large disposable upper dental impression trays located in said second row of pockets, a depletable container of impression material base and a depletable container of impression material catalyst usable with an upper dental impression tray and a lower dental impression tray to form a dental impression, and a container of adhesive material located between the rows of dental impression mold trays;

first and second pouches located on the interior surface of the cover for holding a second plurality of items, said second plurality of items including a sheet of instructions and a mixing pad;

a first secondary case having a base and a cover movable into and out of covering relationship to the base, a support member located in and substantially filling the base, a plurality of upwardly open pockets having the shape of an upper dental impression tray located in the support member, a plurality of disposable upper dental impression trays of small, medium and large sizes located in said pockets of the first secondary case for replenishment of upper dental impression trays depleted from the primary case;

a second secondary case having a base and a cover movable into and out of covering relationship to the base, a support member located in and substantially filling the base, a plurality of upwardly open pockets having the shape of a lower dental impression tray located in the support member, a plurality of disposable lower dental impression trays of small, medium and large sizes located in said pockets of the second secondary case for replenishment of lower dental impression trays depleted from the primary case.

11. The dental impression kit of claim 10 including: a third secondary case, said third secondary case carrying a plurality of replacement containers of dental impression base, a plurality of replacement containers of dental impression catalyst, and at least one replacement container of adhesive for replacement of corresponding items from the primary case.

Contact digitizer, particularly for dental applications

2008-01-09T16:09:00.000-08:00

Abstract

A dental surface tracer includes a probe with a tip that can be moved to trace a given dental surface, including a mounting device for mounting the tracer to a stable reference location and defining a base plane; a first plurality of links which are substantially coplanar and define a plane of movement; the links being pivotably attached to the mounting device so that the plane of movement makes a variable angle with the base plane; a distal one of the first plurality of links being movable in two dimensions within the plane of movement; circuitry for generating electrical signals representative of movements of the probe tip, as a function exclusively of movements of the first plurality of links; a dental handpiece supporting the probe; and a second plurality of links which hold the handpiece and are attached to the first plurality of links; the second plurality of links holding the probe tip at all times at a fixed location in the plane of movement with respect to the distal...

Patent number: 5131844
Filing date: Apr 8, 1991
Issue date: Jul 21, 1992
Inventors: Paul J. Marinaccio, Bruce Nappi, Khushroo M. Captain, Alan J. Lane
Assignee: Foster-Miller, Inc.

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What is claimed is:

1. A probe system comprising:

a probe;

a linking arrangement supporting said probe and having a plurality of joints providing at least 6 degrees of freedom for the probe;

a device for attaching said linking arrangement to a stable reference location; and

a sensing system which measures all movements of said probe with respect to said reference location;

wherein said linking arrangement comprises a first plurality of joints providing three degrees of freedom for said probe, movement of those joints being sensed by said sensing system; and

wherein said linking arrangement comprises a second plurality of joints providing said probe with three degrees of freedom independently of said first plurality, movement of said second plurality of joints not being sensed.

2. A system as in claim 1, wherein said attaching device is capable of attaching the linking arrangement to a work bench.

3. A system as in claim 1, wherein said probe system is for scanning dental surfaces; said attaching device is capable of attaching the linking arrangement to a reference location on a given jaw; and said probe is movable to completely scan a predetermined dental surface on said given jaw.

4. A system as in claim 3, further comprising an adhesive which adheres said attaching device to said reference location.

5. A system as in claim 3, further comprising a handpiece which is firmly attached to said probe.

6. A system as in claim 5, wherein said probe has a curved shank extending from said handpiece and a tip at a distal end of said shank.

7. A system as in claim 6, wherein said curved shank is shaped so as to permit convenient access to all portions of such dental surface.

8. A system as in claim 7, wherein said distal end of said curved shank defines an angle with respect to said handpiece, which angle is selected to permit the distal end of the shank to be perpendicular to the plane of a given jaw while the handpiece extends away from the jaw, remaining clear of the teeth of the jaw.

9. A system as in claim 7, wherein said linking arrangement comprises at least first through sixth links which define at least first through fifth joints in that order, and a sixth joint is defined between said sixth link and the combination of said probe and handpiece.

10. A system as in claim 9, wherein said second, third and fourth links are substantially coplanar.

11. A system as in claim 10, wherein said fourth, fifth, and sixth joints form gimbal means permitting movement of said handpiece while said probe tip and said first through third joints remain in the same position.

12. A system as in claim 11, wherein said gimbal means provides three degrees of freedom for said handpiece and permits rotation of said probe tip while said probe tip remains at the same location with respect to said first through third joints.

13. A system as in claim 12, wherein said sixth joint is a journal which permits the probe to rotate about its longitudinal axis with respect to said sixth link.

14. A system as in claim 11, wherein said fourth and fifth joints are swivel joints each having an axis of rotation.

15. A system as in claim 14, wherein said probe tip remains at all times at the common axis of rotation of said fourth, fifth and sixth joints.

16. A system as in claim 15, wherein said sensing system comprises at least one Hall sensor and at least one magnet associated with said linking arrangement.

17. A system as in claim 15, wherein said sensing means comprises a Hall affect sensor system associated with said first, second and third joints.

18. A system as in claim 17, comprising first, second and third Hall sensors associated respectively with said first, second and third joints, said first Hall sensor sensing relative movement of said first and second links, said second Hall sensor sensing relative movement of said second and third links, and said third Hall sensor sensing relative movement of said third and fourth links.

19. A system as in claim 18, further comprising an elongated magnet on said third link and operatively associated with both said second and third Hall sensors, which are respectively on said second and fourth links.

20. A system as in claim 19, further comprising a horseshoe magnet operatively associated with said first Hall sensor.

21. A system as in claim 18, further comprising linearizing means for receiving output signals from said Hall sensors and improving the linearity thereof.

22. A system as in claim 3, wherein said sensing system has means for generating electrical signals representative of said movements of said probe.

23. A dental surface tracer including a dental probe having six degrees of freedom, comprising:

a mounting device which is capable of being mounted to a reference location with respect to a given jaw and defining a base plane;

a first link which is integral with said mounting device;

substantially coplanar second, third and fourth links defining a plane of movement; said second link being pivotally mounted to said first link so that said plane of movement is movable above and below said base plane; first means for generating electrical signals representative of such movement;

said second, third and fourth links being jointed together to have predetermined ranges of relative angular motion so that a distal end of said fourth link is movable over a predetermined area in said plane of movement; whereby said distal end has three degrees of freedom; second means for generating electrical signals representative of such movement;

a probe; and

gimbal means supporting said probe and attached to said distal end of said fourth link, for permitting said probe to move with three degrees of freedom without any movement of said first through fourth links;

whereby said probe can move with respect to said reference location with six degrees of freedom.

24. A tracer as in claim 23, wherein all of said links and gimbal means are sized for being accommodated within the human mouth.

25. A tracer as in claim 24, wherein said second, third and fourth links are jointed to provide greater than 90.degree. of relative angular motion between each pair of adjacent links.

26. A tracer as in claim 25, wherein substantially 100.degree. of relative angular motion is provided.

27. A tracer as in claim 23, wherein said probe has a tip for tracing a desired dental surface on said jaw, and said first and second means generate electrical signals representative of movement of said probe tip on said dental surface.

28. A tracer as in claim 27, wherein said gimbal means permit rotation of said probe tip within said plane of movement without any movement of said first through fourth links.

29. A tracer as in claim 28, wherein said probe tip remains at all times at the same location with respect to said first through fourth links.

30. A dental surface tracer including a probe with a tip that can be moved to trace a given dental surface, comprising:

a mounting device for mounting said tracer to a stable reference location and defining a base plane;

a first plurality of links which are substantially coplanar and define a plane of movement; said links being pivotably attached to said mounting device so that said plane of movement makes a variable angle with said base plane; a distal one of said first plurality of links being movable in two dimensions within said plane of movement;

means for generating electrical signals representative of movements of said probe tip, as a function exclusively of movements of said first plurality of links;

a dental handpiece supporting said probe; and

a second plurality of links which hold the handpiece and are attached to said first plurality of links;

said second plurality of links holding said probe tip at all times at a fixed location in said plane of movement with respect to said distal link of said first plurality of links; and permitting said handpiece to move about three axes without moving said probe tip from said fixed location.

31. A tracer as in claim 30, wherein said entire tracer exclusive of said handpiece is sized to be accommodated within the human mouth.

Generation and selection of novel DNA-binding proteins

2008-01-08T18:27:00.000-08:00

Abstract

Novel DNA-binding proteins, especially repressors of gene expression, are obtained by variegation of genes encoding known binding proteins and selection for proteins binding the desired target DNA sequence. A novel selection vector may be used to reduce artifacts. Heterooligomeric proteins which bind to a target DNA sequence which need not be palindromic are obtained by a variety of methods, e.g., variegation to obtain proteins binding symmetrized forms of the half-targets and heterodimerization to obtain a protein binding the entire asymmetric target.

Patent number: 5198346
Filing date: Jul 26, 1990
Issue date: Mar 30, 1993
Inventors: Robert C. Ladner, Sonia K. Guterman, Rachel B. Kent, Arthur C. Ley
Assignee: Protein Engineering Corp.
Primary Examiner: John D. Ulm

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What is claimed is:

1. A method of obtaining first and second genes encoding first and second homooligomeric DNA binding proteins which hybridize to form a hybrid heteroologomeric DNA binding protein which binds to a predetermined ultimate target double stranded DNA sequence, said sequence being nonpalindromic, said sequence comprising a left target-sequence and right target subsequence each of at least 4 base pairs length, said method comprising:

producing a first gene encoding a first DNA-binding oligomeric protein binding to a first target sequence and a second gene encoding a second DNA-binding oligomeric protein binding to a second target sequence, wherein said first and second DNA-binding proteins each have at least two essentially dyad-symmetric DNA-binding domains, where said first target sequence is a palindrome or gapped palindrome and comprises said left target subsequence and a palindrome-completing subsequence, and where said second target sequence is a palindrome or gapped palindrome and comprises said right target subsequence and a palindrome-completing subsequence, whereby one of the DNA-binding domains of the second DNA-binding protein binds to the right target subsequence, said genes being produced by a process of at least partially random mutation followed by selection for the binding of the corresponding protein to the corresponding target sequence,

wherein said first and second proteins can hybridize so as to obtain a heterooligomeric DNA-binding protein comprising a DNA-binding domain recognizing the left target subsequence and a DNA-binding domain recognizing the right target subsequence

whereby said heterooligomeric protein has an affinity for the ultimate target DNA.

2. The method of claim 1 wherein at least one of said first and second genes is obtained by

(a) providing a cell culture, said cell culture comprising a plurality of cells, each cell bearing a selection vector, said selection vector comprising a first and a second operon, each comprising at least one expressible gene, the genes of said first and second operons being different, a copy of the target DNA sequence being included in each operon and positioned therein so that under forward selection conditions the transformed cells enjoy a selective advantage if they express a protein or polypeptide which binds to said copies of the target DNA sequence, said cell culture being transformed with a variegated gene encoding potential DNA-binding proteins or polypeptides, where said cells collectively can express a plurality of different but sequence-related potential DNA-binding proteins or polypeptides,

(b) causing the cells of such culture to express said potential DNA-binding proteins or polypeptides;

(c) exposing the cells to forward selection conditions to select for cells which express a protein or polypeptide which preferentially binds to said target DNA sequence; and

(d) recovering the selected cells bearing a gene coding for such protein or polypeptide.

3. The method of claim 2 wherein the level of variegation is such that from 10.sup.6 to 10.sup.9 different potential DNA-binding proteins can be expressed.

4. The method of claim 2 wherein a gene coding for a known DNA binding protein having a helix-turn-helix DNA binding motif is variegated.

5. The method of claim 2 wherein a gene encoding a known DNA binding protein picked from the group consisting of Cro from phage .lambda., cI repressor from phage .lambda., Cro from phage 434, cI repressor from phage 434, P22 repressor, E. coli tryptophan repressor, E. coli CAP, P22 Arc, P22 Mnt, E. coli lactose repressor, MAT-a1-alpha2 from yeast, Polyoma Large T antigen, SV40 Large T antigen, Adenovirus E1A, and TFIIIA from Xenopus laevis is variegated to obtain genes coding on expression for a plurality of potential target DNA-binding proteins.

6. The method of claim 2 wherein said variegated gene comprises at least one variegated codon, said codon having three base positions, each variegated codon being characterized by a mixture of bases at at least one base position wherein the mixture of bases for at least one base position is non-equimolar.

7. The method of claim 2 wherein the ultimate target double stranded DNA sequence is an HIV sequence.

8. The method of claim 7 wherein the ultimate target doublet stranded DNA sequence is HIV 353-369 or a subsequence thereof comprising at least eight base paris.

9. The method of claim 2 wherein at least one of said operons comprises a selectable beneficial gene, an occludible promoter operably linked to said beneficial gene and directing its transcription, an occluding promoter occluding transcription of said beneficial gene, and a copy of the target DNA sequence positioned so that the binding of said protein or polypeptide to said copy represses said occluding promoter and thereby facilitates transcription of said beneficial gene.

10. The method of claim 9 wherein the beneficial gene is aadA.

11. The method of claim 10 wherein the occludible promoter is the aadA promoter and the occluding promoter is Pcon.

12. The method of claim 2 wherein said selection vector comprises:

a) a first operon, which operon comprises:

i) a first binding marker gene(s),

ii) a first promoter directing expression of said binding marker gene(s), and

iii) a first copy of the target DNA sequence, where said target DNA sequence interferes substantially with expression of the first gene(s) if and only if a protein expressed by the transformed cell binds to the target DNA sequence,

(b) a second operon, which operon comprises:

i) a second binding marker gene(s),

ii) a second promoter directing expression of said binding marker gene(s); and

iii) a second copy of the target DNA sequence, where said target DNA sequence interferes substantially with expression of said gene(s) if and only if a protein expressed by the transformed cell binds to the target DNA sequence,

where the binding marker genes of said first and second operons are different, and where, when said cells are exposed to forward selection conditions the gene products of said first and second binding marker genes are deleterious to the cell.

13. The method of claim 12 wherein the binding marker genes are functionally unrelated.

14. The method of claim 12 wherein the promoters of said first and second operons are different.

15. The method of claim 12 wherein a plurality of genetic elements essential to the maintenance of the vector or the survival of the transformed cells under conditions that select for presence of said vector, said operons and said genetic elements being positioned on said vector so no single deletion even can render nonfunctional more than one of said operons without also rendering nonfunctional one of said essential genetic elements.

16. The method of claim 12, said vector further comprising a gene (pdbp) coding for a potential DNA-binding protein or polypeptide, said gene comprising:

a) a coding region that codes for a polypeptide, each domain of said polypeptide having at least 50% sequence identity to a known DNA-binding domain, and

b) a promoter operably linked to said coding region for controlling its expression.

17. The method of claim 12 wherein at least one of said genetic elements comprises a beneficial gene, and a control promoter operably linked to said beneficial gene, but where no instance of said target DNA sequence is associated with said genetic element.

18. The method of claim 17 wherein the control promoter is essentially identical to the promoter of one of said selectable binding marker operons, so that proteins binding to the latter promoter will also bind to the control promoter and thereby inhibit expression of said beneficial gene.

19. The method of claim 12 wherein under reverse selection conditions the gene products of said binding marker genes are beneficial to the transformed cells.

20. The method of claim 19 wherein each of the first and second operons confers a phenotype selected independently but not-identically from the group consisting of: galT,K.sup.+, tetA.sup.+, lacZ.sup.+, pheS.sup.+, argP.sup.+, thyA.sup.+, crp.sup.+, pyrF.sup.+, ptsM.sup.+, secA.sup.+ /malE.sup.+ /lacZ.sup.+, ompA.sup.+, btuB.sup.+, lamB.sup.+, tonA.sup.+, cir.sup.+, tsx.sup.+, aroP.sup.+, cysK.sup.+, and dctA.sup.+.

21. The method of claim 12 wherein the vector comprises a plurality of codons, each variegated codon has a root mean square deviation from a flat distribution over the allowed amino acids of less than 0.08.

22. The method of claim 21 wherein the variation at each variegated codon allows all twenty possible amino acids.

23. The method of claim 22 wherein at any variegated codon the expected ratio of occurrence of (Lys+Arg) codons to (Asp+Glu) codon is 0.8 to 1.25.

24. A method of obtaining genes encoding a heterooligomeric protein which binds to a predetermined ultimate target double stranded DNA sequence, said sequence being nonpalindromic, said sequence comprising a left target subsequence and a right target subsequence each of at least 4 base pairs lengths, said method comprising:

(a) providing a first gene encoding a first DNA-binding oligomeric protein binding to a first target sequence and a second gene encoding a second DNA-binding oligomeric protein binding to a second target sequence, wherein said first and second DNA-binding proteins each have at least two dyad-symmetric DNA-binding domains, wherein said first and second DNA-binding proteins each have a dimerization interface, where said first target sequence is a palindrome or gaped palindrome and comprises said left target subsequence and a palindrome-completing subsequence, whereby one of the dyad-symmetric DNA-binding domains of the first DNA-binding protein binds to said left target subsequence, and where said second target sequence is a palindrome or gaped palindrome and comprises said right target subsequence and a palindrome completing subsequence, whereby one of the dyad-symmetric DNA-binding domains of the second DNA-binding protein binds to the right target subsequence,

(b) variegating the dimerization interface of the protein encoded by one of said first or second genes to obtain variegants thereof and reverse selecting for expression from said variegant of a first oligomerization mutant protein, encoded by a variegant of said variegated gene, which is no longer capable of forming a homooligomer that can bind to said first or second target sequence, respectively, and verifying that said oligomerization mutant protein maintains a tertiary structure similar to the protein form which is descended,

(c) variegating the dimerization interface of the protein encoded by the other of said first or second genes to obtain variegants thereof,

(d) providing host cells carrying the gene encoding said first oligomerization mutant protein and a variegant gene of step (c), each operably linked to a promoter functional in the host cell, and

(e) forward selecting for expression from a step (c) variegant gene of a second oligomerization mutant protein which is capable of forming a heterooligomer with said first oligomerization mutant protein, said heterooligomer binding said ultimate target DNA sequence, and

(f) isolating the genes encoding said heterooligomer.

25. The method of claim 24 wherein both of said first and second genes are provided by a process comprising (i) mutation of one or more preselected codons to encode a plurality of predetermined expected amino acids at each preselected codon, in predetermined expected proportions, and thereby obtain a plurality of different potential DNA binding proteins, and (ii) selection for genes encoding proteins which bind the corresponding target sequence.

26. The method of claim 25 in which the first and second DNA binding proteins either are unable to hybridize at all and still bind DNA, or, if they do hybridize, have a substantially diminished affinity or specificity for the corresponding subsequence of the target DNA sequence.

27. The method of claim 25 wherein at least one of said first and second genes is obtained by

(b) causing the cells of such culture to express said potential DNA-binding proteins or polypeptides;

(c) exposing the cells to forward selection conditions to select for cells which express a protein or polypeptide which preferentially binds to said target DNA sequence; and

(d) recovering the selected cells bearing said first or second gene coding for such protein or polypeptide.

28. The method of claim 27 wherein the level of variegation is such that from 10.sup.6 to 10.sup.9 different potential DNA-binding proteins can be expressed.

29. The method of claim 27 wherein a gene coding for a known DNA binding protein having a helix-turn-helix DNA binding motif is variegated.

30. The method of claim 27 wherein a gene encoding a known DNA binding protein picked from the group consisting of Cro from phage .lambda., cI repressor from phage .lambda., Cro from phage 434, cI repressor from phage 434, P22 repressor, E. coli tryptophan repressor, E. coli CAP, P22 Arc, P22 Mnt, E. coli lactose repressor, MAT-a1-alpha2 from yeast, Polyoma Large T antigen, SV40 Large T antigen, Adenovirus E1A, and TFIIIA from Xenopus laevis is variegated to obtain genes coding on expression for a plurality of potential target DNA-binding proteins.

31. The method of claim 27 wherein said variegated gene comprises at least one variegated codon, said codon having three base positions, each variegated codon being characterized by a mixture of bases at at least one base position wherein the mixture of bases for at least one base position is non-equimolar.

32. The method of claim 27 wherein the ultimate target double stranded DNA sequence is an HIV sequence.

33. The method of claim 32 wherein the ultimate target double stranded DNA sequence is HIV 353-369 or a subsequence thereof comprising at least eight base paris.

34. The method of claim 27 wherein at least one of said operons comprises a selectable beneficial gene, an occludible promoter operably linked to said beneficial gene and directing its transcription, an occluding promoter occluding transcription of said beneficial gene, and a copy of the target DNA sequence positioned so that the binding of said protein or polypeptide to said copy represses said occluding promoter and thereby facilitates transcription of said beneficial gene.

35. The method of claim 34 wherein the beneficial gene is aadA.

36. The method of claim 35 wherein the occludible promoter is the aadA promoter and the occluding promoter is Pcon.

37. The method of claim 27 wherein said selection vector comprises:

a) a first operon, which operon comprises:

i) a first binding marker gene(s),

ii) a first promoter directing expression of said binding marker gene(s), and

(b) a second operon, which operon comprises:

i) a second binding marker gene(s),

ii) a second promoter directing expression of said binding marker gene(s); and

38. The method of claim 37 wherein the binding marker genes are functionally unrelated.

39. The method of claim 37 wherein the promoters of said first and second operons are different.

40. The method of claim 37 wherein a plurality of genetic elements essential to the maintenance of the vector or the survival of the transformed cells under conditions that select for presence of said vector, said operons and said genetic elements being positioned on said vector so no single deletion event can render nonfunctional more than one of said operons without also rendering nonfunctional one of said essential genetic elements.

41. The method of claim 37, said vector further comprising a gene (pdbp) coding for a potential DNA-binding protein or polypeptide, said gene comprising:

a) a coding region that codes for a polypeptide, each domain of said polypeptide having at least 50% sequence identity to a known DNA-binding domain, and

b) a promoter operably linked to said coding region for controlling its expression.

42. The method of claim 37 wherein at least one of said genetic elements comprises a beneficial gene, and a control promoter operably linked to said beneficial gene, but where no instance of said target DNA sequence is associated with said genetic element.

43. The method of claim 42 wherein the control promoter is essentially identical to the promoter of one of said selectable binding marker operons, so that proteins binding to the latter promoter will also bind to the control promoter and thereby inhibit expression of said beneficial gene.

44. The method of claim 37 wherein under reverse selection conditions the gene products of said binding marker genes are beneficial to the transformed cells.

45. The method of claim 44 wherein each of the first and second operons confers a phenotype selected independently but not-identically from the group consisting of: galT,K.sup.+, tetA.sup.+, lacZ.sup.+, pheS.sup.+, argP.sup.+, thyA.sup.+, crp.sup.+, pyrF.sup.+, ptsM.sup.+, secA.sup.+ /malE.sup.+ /lacZ.sup.+, ompA.sup.+, btuB.sup.+, lamB.sup.+, tonA.sup.+, cir.sup.+, tsx.sup.+, aroP.sup.+, cysK.sup.+, and dctA.sup.+.

46. The method of claim 37 wherein the vector comprises a plurality of codons, each variegated codon has a root mean square deviation from a flat distribution over the allowed amino acids of less than 0.08.

47. The method of claim 46 wherein the variation at each variegated codon allows all twenty possible amino acids.

48. The method of claim 47 wherein at any variegated codon the expected ratio of occurrence of (Lys+Arg) codons to (Asp+Glu) codon is 0.8 to 1.25.

Determining DNA sequences by mass spectrometry

2008-01-08T17:12:00.000-08:00

Abstract

This invention relates to the methods, apparatus, reagents and mixtures of reagents for sequencing natural or recombinant DNA and other polynucleotides. In particular, this invention relates to a method for sequencing polynucleotides based on mass spectrometry to determine which of the four bases (adenine, guanine, cytosine or thymine) is a component of the terminal nucleotide. In particular, the present invention relates to identifying the individual nucleotides by the mass of stable nuclide markers contained within either the dideoxynucleotides, the DNA primer, or the deoxynucleotide added to the primer. This invention is particularly useful in identifying specific DNA sequences in very small quantities in biological products produced by fermentation or other genetic engineering techniques. The invention is therefore useful in evaluating safety and other health concerns related to the presence of DNA in products resulting from genetic engineering techniques.

Patent number: 5003059
Filing date: Jun 20, 1988
Issue date: Mar 26, 1991
Inventor: Thomas M. Brennan
Assignee: Genomyx, Inc.
Primary Examiner: Gary L. Kunz

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What is claimed is:

1. In a process for determining DNA sequence by the dideoxynucleotide chain termination method, the improvement comprising incorporating .sup.32 S, .sup.33 S, .sup.34 S and .sup.36 S in the formation of the chain terminated sequence so that a unique sulfur isotope is associated with the terminal nucleotide in the chain terminated sequence, separating the chain terminated sequences by capillary gel electrophoresis, combusting the separated chain terminated sequences to convert the incorporated sulfur to SO.sub.2, and determining the terminal nucleotide by measuring .sup.64 SO.sub.2, .sup.65 SO.sub.2, .sup.67 SO.sub.2, and .sup.68 SO.sub.2 in a mass spectrometer thereby determining the sequence of the DNA.

2. A process according to claim 1 wherein the isotope is incorporated only into the 2', 3'-dideoxyribonucleotides.

3. A process according to claim 1 wherein the isotope is incorporated only into the 2'-deoxyribonucleotides.

4. A process according to claim 1 wherein the isotope is incorporated into a DNA primer.

Processes for inserting DNA into eucaryotic cells

2008-01-08T17:08:00.000-08:00

Abstract

The present invention relates to processes for inserting DNA into eucaryotic cells, particularly DNA which includes a gene or genes coding for desired proteinaceous materials for which no selective criteria exist. The insertion of such DNA molecules is accomplished by cotransforming eucaryotic cells with such DNA together with a second DNA which corresponds to a gene coding for a selectable marker.

Patent number: 4399216
Filing date: Feb 25, 1980
Issue date: Aug 16, 1983
Inventors: Richard Axel, Michael H. Wigler, Saul J. Silverstein
Assignee: The Trustees of Columbia University

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What is claimed is:

1. A process for inserting foreign DNA I into a suitable eucaryotic cell which comprises cotransforming said eucaryotic cell with said foreign DNA I and with unlinked foreign DNA II which codes for a selectable phenotype not expressed by said ducaryotic cell, said cotransformation being carried out under suitable conditions permitting survival or identification of eucaryotic cells which have acquired said selectable phenotype, said foreign DNA I being incorporated into the chromosomal DNA of said eucaryotic cell.

2. A process in accordance with claim 1 wherein said foreign DNA I codes for proteinaceous material which is not associated with a selectable phenotype.

3. A process in accordance with claim 2 wherein said foreign DNA I codes for interferon protein.

4. A process in accordance with claim 2 wherein said foreign DNA I codes for insulin.

5. A process in accordance with claim 2 wherein said foreign DNA I codes for growth hormone.

6. A process in accordance with claim 2 wherein said foreign DNA I codes for a clotting factor.

7. A process in accordance with claim 2 wherein said foreign DNA I codes for a viral antigen or an antibody.

8. A process in accordance with claim 2 wherein said foreign DNA I codes for an enzyme.

9. A process in accordance with claim 1 wherein said foreign DNA I is substantially purified.

10. A process in accordance with claim 1 wherein said foreign DNA I has been obtained from restriction endonuclease cleavage of eucaryotic chromosomal DNA.

11. A process in accordance with claim 1 wherein said foreign DNA I and DNA II have been treated with calcium phosphate.

12. A process in accordance with claim 1 wherein said eucaryotic cell is a mammalian cell.

13. A process in accordance with claim 12 wherein said mammalian cell is an erythroblast.

14. A process in accordance with claim 12 wherein said mammalian cell is a fibroblast.

15. A process in accordance with claim 1 wherein said foreign DNA I is present in an amount relative to said DNA II which codes for a selectable phenotype in the range from about 1:1 to about 100,000:1.

16. A process in accordance with claim 1 wherein said DNA II which codes for a selectable phenotype comprises the gene for thymidine kinase from herpes simplex virus.

17. A process in accordance with claim 1 wherein said DNA II which codes for proteinaceous material which is associated with a selectable phenotype comprises the gene for adenine phosphoribosyltransferase.

18. A process in accordance with claim 1 wherein said DNA II which codes for a selectable phenotype comprises a gene associated with drug resistance.

19. A process in accordance with claim 18 wherein said gene associated with drug resistance is the gene coding for a mutant dihydrofolate reductase which renders cells resistant to methotrexate.

20. A eucaryotic cell into which foreign DNA I has been inserted in accordance with the process of claim 1.

21. A mammalian cell into which foreign DNA I has been inserted in accordance with the process of claim 1.

22. A process for producing a foreign proteinaceous material which comprises cotransforming a eucaryotic cell in accordance with the process of claim 1, culturing or cloning said cotransformed eucaryotic cell under suitable conditions to yield a multiplicity of eucaryotic cells producing said foreign proteninaceous material and recovering said proteinaceous material from said eucaryotic cells.

23. A process in accordance with claim 22 wherein said proteinaceous material comprises interferon protein, insulin, growth hormone, clotting factor, viral antigen or antibody.

24. A process in accordance with claim 22 wherein said eucaryotic cell is a mammalian cell.

25. A method of detecting eucaryotic cells which have been transformed with foreign DNA I which is not associated with a selectable phenotype which comprises cotransforming said eucaryotic cell with said DNA I and with DNA II which is associated with a selectable phenotype in accordance with the process of claim 1, and screening for eucaryotic cells so cotransformed.

26. A process for inserting foreign DNA I into a eucaryotic cell which comprises cotransforming said eucaryotic cell with said foreign DNA I and with unlinked foreign DNA II which codes for a selectable phenotype not expressed by said eucaryotic cell, said cotransformation being carried out in a suitable medium and in the presence of conditions permitting identification and recovery of eucaryotic cells which have acquired said selectable phenotype.

27. A process for cotransforming a suitable eucaryotic cell which comprises transforming under suitable conditions said eucaryotic cell with foreign DNA I and with foreign DNA II, said DNA I and DNA II being unlinked and said DNA II coding for a selectable phenotype not expressed by said eucaryotic cell prior to cotransformation.

28. A process for inserting purified foreign DNA I coding for proteinaceous material which is not associated with a selectable phenotype into a suitable eucaryotic cell which comprises cotransforming said eucaryotic cell with said foreign DNA I and with unlinked foreign DNA II coding for proteinaceous material which is associated with a selectable phenotype, said cotransformation being carried out under suitable conditions permitting survival or identification of eucaryotic cells which have acquired said selectable phenotype, said foreign DNA I being incorporated into the chromosomal DNA of said eucaryotic cell.

29. A process in accordance with claim 28 wherein said proteinaceous material which is not associated with a selectable phenotype comprises interferon protein, insulin, growth hormone, clotting factor, viral antigen or antibody.

30. A eucaryotic cell into which foreign DNA I has been inserted in accordance with the process of claim 28.

31. A process for inserting a multiplicity of foreign DNA I molecules corresponding to multiple copies of a gene coding for a proteinaceous material into a suitable eucaryotic cell which comprises cotransforming said eucaryotic cell with said multiplicity of foreign DNA I molecules and with a multiplicity of unlinked foreign DNA II molecules coding for a selectable phenotype not expressed by said eucaryotic cell, said cotransformation being carried out under suitable conditions permitting survival or identification of eucaryotic cells which have acquired said multiplicity of genes coding for said selectable phenotype.

32. A process in accordance with claim 31 wherein said foreign DNA I codes for proteinaceous material which is not associated with a selectable phenotype.

33. A process in accordance with claim 32 wherein said foreign DNA I codes for interferon protein.

34. A process in accordance with claim 32 wherein said foreign DNA I codes for insulin.

35. A process in accordance with claim 32 wherein said foreign DNA I codes for growth hormone.

36. A process in accordance with claim 32 wherein said foreign DNA I codes for a clotting factor.

37. A process in accordance with claim 32 wherein said foreign DNA I codes for a viral antigen or an antibody.

38. A process in accordance with claim 32 wherein said foreign DNA I codes for an enzyme.

39. A process in accordance with claim 31 wherein said foreign DNA I is substantially purified.

40. A process in accordance with claim 31 wherein said foreign DNA I has been obtained from restriction endonuclease cleavage of eucaryotic chromosomal DNA.

41. A process in accordance with claim 31 wherein said foreign DNA I and DNA II have been treated with calcium phosphate.

42. A process in accordance with claim 31 wherein said eucaryotic cell is a mammalian cell.

43. A process in accordance with claim 42 wherein said mammalian cell is an erythroblast.

44. A process in accordance with claim 42 wherein said mammalian cell is a fibroblast.

45. A process in accordance with claim 31 wherein said foreign DNA I is present in an amount relative to said DNA II which codes for proteinaceous material associated with a selectable phenotype in the range from about 1:1 to about 100,000:1.

46. A process in accordance with claim 31 wherein said foreign DNA II which does for proteinaceous material which is associated with a selectable phenotype comprises a gene associated with drug resistance.

47. A process in accordance with claim 46 wherein said gene associated with drug resistance is a gene coding for a mutant dihydrofolate reductase which renders cells resistant to methotrexate.

48. A process in accordance with claim 31 wherein said foreign DNA I is incorporated into the chromosomal DNA of said eucaryotic cell.

49. A eucaryotic cell into which foreign DNA I has been inserted in accordance with the process of claim 31.

50. A mammalian cell into which foreign DNA I has been inserted in accordance with the process of claim 31.

51. A process for producing a foregin proteinaceous material which comprises cotransforming a eucaryotic cell in accordance with the process of claim 31, maintaining said cotransformed eucaryotic cell under suitable conditions to produce said foreign proteinaceous material, and recovering said proteinaceous material so produced.

52. A process in accordance with claim 51 wherein said proteinaceous material comprises interferon protein, insulin, growth hormone, clotting factor, viral antigen or antibody.

53. A process in accordance with claim 51 wherein said eucaryotic cell is mammalian cell.

54. A process for generating a multiplicity of foregin DNA I molecules corresponding to multiple copies of a gene in a eucaryotic cell which comprises tranforming said eucaryotic cell with a molecule which is formed by linking one of said foreign DNA I molecules to a DNA II molecule corresponding to an amplifiable gene for a dominant selectable phenotype not expressed by said eucaryotic cell, and culturing the transformed eucaryotic cells in the presence of successively elevated concentrations of an agent permitting survival or identification of eucaryotic cells which have acquired multiple copies of said amplifiable gene, said transformation and culturing being carried out under suitable conditions.

55. A process in accordance with claim 54 wherein said foreign DNA I codes for proteinaceous material which is not associated with a selectable phenotype.

56. A process in accordance with claim 55 wherein said foreign DNA I codes for interferon protein.

57. A process in accordance with claim 55 wherein said foreign DNA I codes for insulin.

58. A process in accordance with claim 55 wherein said foreign DNA I codes for growth hormone.

59. A process in accordance with claim 55 wherein said foreign DNA I codes for a clotting factor.

60. A process in accordance with claim 55 wherein said foreign DNA I codes for a viral antigen or antibody.

61. A process in accordance with claim 55 wherein said foregin DNA I codes for an enzyme.

62. A process in accordance with claim 54 wherein said foreign DNA I is substantially purified.

63. A process in accordance with claim 54 wherein said foreign DNA I has been obtained from restriction endonuclease cleavage of eucaryotic chromosomal DNA.

64. A process in accordance with claim 54 wherein said foreign DNA I and DNA II have been treated with calcium phosphate.

65. A process in accordance with claim 54 wherein said eucaryotic cell is mammalian cell.

66. A process in accordance with claim 65 wherein said mammalian cell is an erythroblast.

67. A process in accordance with claim 65 wherein said mammalian cell is a fibroblast.

68. A process in accordance with claim 54 wherein said foreign DNA I is present in an amount relative to said DNA II which codes for proteinaceous material associated with a selectable phenotype in the range from about 1:1 to about 100,000:1.

69. A process in accordance with claim 54 wherein said DNA II which codes for proteinaceous material which is associated with a selectable phenotype comprises a gene associated with resistance to a drug or chemical antagonist.

70. A process in accordance with claim 69 wherein said gene associated with resistance to a drug or chemical anatgonist is a gene coding for a mutant dihydrofolate reductase which renders cells resistant to methotrexate.

71. A process in accordance with claim 54 wherein said foreign DNA I is incorporated into the chromosomal DNA of said eucaryotic cell.

72. A eucaryotic cell into which foreign DNA I has been inserted in accordance with the process of claim 54.

73. A mammalian cell into which foreign DNA I has been inserted in accordance with the process of claim 54.

Specific DNA probes in diagnostic microbiology

2008-01-08T15:15:00.000-08:00

Abstract

Method and compositions for infectious disease diagnosis and epidemiology involving labeled nucleotide probes complementary to nucleic acid coding for a characteristic pathogen product. Clinical isolates are cultivated, expanding the number of microorganisms, the resulting colonies lysed, the genome normally denatured and then fixed. Alternatively, clinical samples (stool, sputum, pus, etc.) are spotted onto an inert support. The sample is treated in such a way that the DNA is liberated from microbes present in the sample and complexed onto the support. The DNA is normally denatured and fixed in this process. Subsequently, a labelled polynucleotide probe specific for a DNA sequence characteristic of a pathogenic product suspected of being present in the clinical sample is contacted with the fixed genomic single stranded nucleic acid under hybridizing conditions. Hybridization of probes to the single stranded nucleic acid is diagnostic of the presence of the pathogen.

Patent number: 4358535
Filing date: Dec 8, 1980
Issue date: Nov 9, 1982
Inventors: Stanley Falkow, Stephen L. Moseley
Assignee: Board of Regents of the University of Washington

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What is claimed is:

1. A method for detecting the presence of a pathogen in a clinical sample suspected of containing said pathogen, said method comprising:

depositing said sample on an inert support;

treating said sample to affix genetic material of any of said pathogen present in said sample to said support in substantially single stranded form at substantially the same site on said support where said sample was deposited;

contacting said fixed single stranded genetic material with a labeled probe having a nucleotide sequence of at least about 25 bases at least substantially complementary to a nucleotide sequence of a structural gene characteristic of said pathogen, said contacting being under hybridizing conditions at a predetermined stringency; and

detecting duplex formation on said support by means of said label.

2. A method according to claim 1, including the additional step of cultivating said deposited sample to produce at least one individual colony.

3. A method according to claims 1 or 2, wherein said depositing is performed by streaking or spotting.

4. A method according to claim 2, wherein said support is an inert porous filter and said cultivating comprises:

maintaining said filter in contact with a nutrient gel; and said contacting comprises

placing said filter on a bibulous material wetted with reagent solution capable of removing other than genetic material to leave single stranded genetic material.

5. A method according to claims 1, 2 or 4, wherein said pathogen is a unicellular organism.

6. A method according to claim 5, wherein said unicellular organism is a bacterium.

7. A method according to claims 1, 2 or 4, wherein said pathogen is a virus.

8. A method according to claims 1, 2 or 4, wherein said pathogen is a multicellular organism.

9. A method according to claims 1, 2 or 4, wherein said structural gene codes for an excreted product.

10. A method according to claims 1, 2 or 4, wherein said structural gene codes for a cytoplasmic product.

11. A method for detecting the presence of a unicellular pathogen in a sample suspected of containing said pathogen, said method comprising:

depositing said sample on an inert porous filter as a plurality of individual portions;

transferring said filter to a bibulous material wetted with a reagent solution capable of lysing said pathogen and denaturing the genetic material of said pathogen to provide single stranded DNA;

heating said filter to fix said single stranded DNA at substantially the same site as the individual portion from which said genetic material is derived;

contacting said fixed single stranded DNA with a labeled probe having a nucleotide sequence of at least about 25 bases at least substantially complementary to a nucleotide sequence of a structural gene characteristic of said pathogen under hybridizing conditions of a predetermined stringency,; and

detecting duplex formation on said support by means of said label.

12. A method according to claim 11, including the step of:

cultivating said individual portions on said inert porous filter by contacting said filter with a nutrient gel to produce individual colonies of said pathogen, and wherein said reagent solution is a dilute aqueous alkaline solution.

13. A method according to claims 11 or 12, wherein said label is a radionuclide.

14. A method according to claims 11 or 12, wherein said label is a fluorescent molecule.

15. A method according to claims 11 or 12, wherein said unicellular pathogen is a bacterium.

16. A method according to claim 15, wherein said label is a radionuclide.

17. A method for detecting the presence of a gram negative bacillus in a clinical isolate suspected of containing said bacillus, said method comprising:

spotting said clinical isolate onto an inert porous filter;

contacting said spotted inert porous filter with a nutrient gel, whereby nutrients diffuse to said bacillus in said spot, whereby a colony forms;

transferring said filter supporting said colony onto a bibulous material containing a reagent solution for lysing said bacillus and denaturing the genome of said bacillus to provide single stranded DNA at substantially the same site as said colony;

heating said filter to fix said single stranded DNA to said filter;

contacting said filter with said fixed single stranded DNA, with a radioactively labeled probe having a nucleotide sequence of at least about 25 bases and at least substantially complementary to a nucleotide sequence of a structural gene characteristic of said bacillus under hybridizing conditions of a predetermined stringency; and

detecting duplex formation on said support by means of said radioactive isotope.

18. A method according to claim 17, wherein said structural gene codes for a released product.

19. A method according to claim 18, wherein said released product is a toxin.

20. A method according to claims 17, 18 or 19, wherein said bacillus is enterotoxigenic Escherichia coli.

Method of detecting HIV protease activity

2008-01-07T07:27:00.000-08:00

Abstract
A method for identifying compounds that inhibit HIV protease is disclosed. A substrate that comprises an HIV protease cleavage site is combined with HIV protease and test compounds. Cleavage of the substrate indicates protease activity and can be detected using antibodies against a cleavage product which do not cross react with uncleaved substrate. A method of detecting the presence of anti-HIV protease antibodies in a sample is also disclosed. A substrate is combined with the sample and HIV protease. Detection of substrate cleavage indicates that the protease is active and that there is an absence of neutralizing anti-HIV protease antibodies.

Patent number: 5171662
Filing date: Apr 4, 1991
Issue date: Dec 15, 1992
Inventor: Satish K. Sharma
Assignee: The Upjohn Company
Primary Examiner: Chris Dubrule

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What is claimed is:

1. A method for identifying compounds which inhibit HIV protease activity comprising the steps of:

a) combining a substrate, said HIV protease, anti-Ang I antibodies and a compound that is an HIV protease inhibitor candidate, said substrate comprising an HIV protease cleavage site, wherein said substrate does not bind with anti-Ang I antibodies and cleavage of said substrate by said HIV protease generates at least one reactive cleavage product which binds with anti-Ang I antibodies; and

b) detecting the presence of said anti-Ang I antibodies that are bound with said reactive cleavage product, binding of anti-Ang I antibodies with a reactive cleavage product indicates that said HIV protease cleaved said substrate.

2. A method according to claim 1 wherein said HIV protease is HIV-1 protease.

3. A method according to claim 2 wherein said HIV protease cleavage site is selected from the group consisting of Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, Pro-Phe-His-Leu-Leu-Glu-Ile-Ser and Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

4. A method according to claim 2 wherein said substrate is selected from the group consisting of: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser; Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Ile-Ser; and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

5. A method according to claim 1 wherein said anti-Ang I antibodies are immobilized upon a solid phase.

6. A method according to claim 5 wherein said anti-Ang I antibodies are immobilized upon the inner surface of a container such that said anti-Ang I antibodies will come into contact with material put into said container, and wherein said substrate, said HIV protease and said compound that is an HIV protease inhibitor candidate are combined in said container.

7. A method according to claim 6 comprising the additional steps of:

a) adding a radiolabeled peptide to said container, wherein said radiolabeled peptide competes with said reactive cleavage product to bind with said anti-Ang I antibodies;

b) removing unbound reactive cleavage product and unbound radiolabeled peptide from said container; and

c) measuring amount of radiolabeled material is bound to said anti-Ang I antibodies.

8. A kit for identifying compounds that inhibit HIV protease activity, wherein said kit comprises a carton comprising:

a) a container having anti-Ang I antibodies immobilized on its inner surface;

b) a container comprising a substrate comprising an HIV protease cleavage site wherein said substrate does not bind to said anti-Ang I antibodies and wherein cleavage of said substrate by said HIV protease generates at least one reactive cleavage product which binds with said anti-Ang I antibodies; and,

c) a container comprising HIV protease, said container comprising HIV protease being a different container than said container comprising said substrate.

9. A kit according to claim 8 wherein said HIV protease is HIV-1.

10. A kit according to claim 9 wherein said HIV protease cleavage site is an amino acid sequence is selected from the group consisting of Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, Pro-Phe-His-Leu-Leu-Glu-Ile-Ser and Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

11. A kit according to claim 9 wherein said substrate is selected from the group consisting of: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser; Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Ile-Ser; and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

12. A method of detecting the presence of anti-HIV protease antibodies in a sample that is suspected of containing antibodies to HIV protease comprising the steps of:

a) combining a substrate, HIV protease, anti-Ang I antibodies and a sample that is suspected of containing antibodies to HIV protease, said substrate comprising an HIV protease cleavage site wherein said substrate does not bind with anti-Ang I antibodies and cleavage of said substrate by said HIV protease generates at least one reactive cleavage product which binds with anti-Ang I antibodies; and

b) detecting the presence of said anti-Ang I antibodies that are bound with said reactive cleavage product.

13. A method according to claim 12 wherein said anti-HIV protease antibodies are anti-HIV-1 antibodies and said HIV protease is HIV-1 protease.

14. A method according to claim 13 wherein said HIV protease cleavage site is selected from the group consisting of Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, Pro-Phe-His-Leu-Leu-Glu-Ile-Ser and Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

15. A method according to claim 13 wherein said substrate is selected from the group consisting of: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser; Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Ile-Ser; and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

16. A method according to claim 12 wherein said anti-Ang I antibodies are immobilized upon a solid phase.

17. A method according to claim 16 wherein said anti-Ang I antibodies are immobilized upon the inner surface of a container such that said anti-Ang I antibodies will come into contact with material put into said container, and wherein said substrate, said HIV protease and said sample that is suspected of containing antibodies to HIV protease are combined in said container.

18. A method according to claim 17 comprising the additional steps of:

a) adding a radiolabeled peptide to said container, wherein said radiolabeled peptide competes with said reactive cleavage product to bind with said anti-Ang I antibodies;

b) removing unbound reactive cleavage product and unbound radiolabeled peptide from said container; and

c) measuring amount of radiolabeled material is bound to said anti-Ang I antibodies.

19. A kit for detecting the presence of anti-HIV protease antibodies in a sample that is suspected of containing antibodies to HIV protease, wherein said kit comprises a carton comprising:

a) a container having anti-Ang I antibodies immobilized on its inner surface;

c) a container comprising HIV protease, said container comprising HIV protease being a different container than said container comprising said substrate.

20. A kit according to claim 19 wherein said anti-HIV protease antibodies are anti-HIV-1 protease antibodies and said HIV protease is HIV-1 protease.

21. A kit according to claim 20 wherein said HIV protease cleavage site is selected from the group consisting of Pro-Phe-His-Leu-Leu-Val-Tyr-Ser, Pro-Phe-His-Leu-Leu-Glu-Ile-Ser and Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

22. A kit according to claim 19 wherein said substrate is selected from the group consisting of: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser; Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Ile-Ser; and Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu-Glu-Ser.

HIV protease inhibitors useful for the treatment of AIDS

2008-01-07T07:25:00.001-08:00

Abstract

Compounds of formula ##STR1## where R.sup.1 and R.sup.2 are independently hydrogen or optionally-substituted C.sub.1-4 alkyl or aryl, or R.sup.1 and R.sup.2 are joined together to form a monocyclic or bicyclic ring system, are HIV protease inhibitors. These compounds are useful in the treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of treating infection by HIV are also described.

Patent number: 5413999
Filing date: May 7, 1993
Issue date: May 9, 1995
Inventors: Joseph P. Vacca, Bruce D. Dorsey, James P. Guare, M. Katharine Holloway, Randall W. Hungate, Rhonda B. Levin
Assignee: Merck & Co., Inc.
Primary Examiner: John Peabody

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What is claimed is:

1. A compound of the formula ##STR295## wherein V is absent or ##STR296## wherein Q is absent or --O--, --NR--, or heterocycle optionally sustituted with --C.sub.1-4 alkyl;

R.sup.1 is:

1) --C.sub.1-4 alkyl unsubstituted or substituted with one or more of

a) halo,

b) C.sub.1-3 alkoxy,

c) aryl unsubstituted or substituted with one or more of C.sub.1-4 alkyl, amino, hydroxy or aryl,

d) --W--aryl or --W--benzyl, wherein W is --O--, --S--, or --NH--,

e) a 5-7 membered cycloalkyl group unsubstituted or substituted with one or more of

i) halo,

ii) C.sub.1-3 alkoxy, or

iii) aryl,

f) heterocycle unsubstituted or substituted with one or more of oxo, halo, C.sub.1-4 alkoxy, C.sub.1-4 alkyl; ##STR297## or Boc, ##STR298## i) --NH--SO.sub.2 C.sub.1-3 alkyl, j) --NR.sub.2, and R is hydrogen or C.sub.1-4 alkyl;

k) --COOR, or

l) --((CH.sub.2).sub.m O).sub.n R wherein in is 2, 3, 4, or 5, and n is zero, 1,2 or 3, or

2) aryl, unsubstituted or substituted with one or more of

a) halo,

b) hydroxy,

c) --NO.sub.2 or --NR.sub.2,

d) C.sub.1-4 alkyl,

e) C.sub.1-3 alkoxy, unsubstituted or substituted with one or more of C.sub.1-3 alkoxy, ##STR299## q) --R.sup.5, as defined below; or 4) heterocycle unsubstituted or substituted with one or more of oxo, halo, amino, C.sub.1-4 alkoxy, C.sub.1-4 alkyl; or Boc;

5) carbocyclic unsubstituted or substituted with one or more of halo, amino, or C.sub.1-4 alkoxy;

R.sup.3 is benzyl, unsubstituted or substituted with one or more of (1) hydroxy, (2) C.sub.1-3 alkoxy substituted with one or more of --OH or (3) ##STR300## R.sup.5 is 1) --1) --W--(CH.sub.2).sub.m --NR.sup.6 R.sup.7 wherein W is as defined above, m is 2,3,4 or 5, and R.sup.6 and R.sup.7 are independently

a) hydrogen,

b) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of

i) C.sub.1-3 alkoxy, or

ii) --NR.sub.2,

c) the smile or different and joined together to form a 5-7 member heterocycle, such as morpholino, containing up to two additional heteroatoms selected from ##STR301## the heterocycle optionally substituted with C.sub.1-4 alkyl, or d) aromatic heterocycle unsubstituted or substituted with one or more of

i) C.sub.1-4 alkyl, or

ii) --NR.sub.2,

2) --(CH.sub.2)q--NR.sup.6 R.sup.7 wherein q is 1,2,3,4, or 5, and R.sup.6 and R.sup.7 are defined above, except that R.sup.6 or R 7 are not H or unsubstituted C.sub.1-6 alkyl, or

3) benzofuryl, indolyl, azacycloalkyl, azabicyclo C.sub.7-11 cycloalkyl, or benzopiperidinyl, unsubstituted or substituted with C.sub.1-4 alkyl;

R.sup.12 is ##STR302## or pharmaceutically acceptable salt thereof.

2. The compound of claim 1, of the formula ##STR303## wherein V is absent;

R.sup.1 is:

1) --C.sub.1-4 alkyl unsubstituted or substituted with one or more of

a) halo,

b) C.sub.1-3 alkoxy,

c) aryl unsubstituted or substituted with one or more of C.sub.1-4 alkyl, amino, hydroxy or aryl,

d) --W--aryl or --W--benzyl, wherein W is --O--, --S--, or --NH--,

e) a 5-7 membered cycloalkyl group unsubstituted or substituted with one or more of

i) halo.

ii) C.sub.1-3 alkoxy, or

iii) aryl,

f) heterocycle unsubstituted or substituted with one or more of oxo, halo, C.sub.1-4 alkoxy, C.sub.1-4 alkyl; ##STR304## or Boc, ##STR305## i) --NH--SO.sub.2 C.sub.1-3 alkyl, j) --NR.sub.2, and R is hydrogen or C.sub.1-4 alkyl;

k) --COOR, or

l) --((CH.sub.2).sub.m O).sub.n R wherein m is 2, 3, 4, or 5, and n is zero, 1,2or3,

R.sup.3 is benzyl, unsubstituted or substituted with one or more of (1) hydroxy, (2) C.sub.1-3 alkoxy substituted with one or more of --OH or (3) ##STR306## or pharmaceutically acceptable salt thereof.

3. The compound of claim 2 of the formula ##STR307## wherein V is absent;

R.sup.1 is:

1) --C.sub.1-4 alkyl unsubstituted or substituted with one or more of

c) aryl unsubstituted or substituted with one or more of C.sub.1-4 alkyl, amino, hydroxy or aryl,

e) a 5-7 membered cycloalkyl group unsubstituted or substituted with one or more of

i) halo,

ii) C.sub.1-3 alkoxy, or

iii) aryl,

f) heterocycle unsubstituted or substituted with one or more of oxo, halo, C.sub.1-4 alkoxy, C.sub.1-4 alkyl; ##STR308## or Boc, R.sup.3 is benzyl, unsubstituted or substituted with one or more of (1) hydroxy, (2) C.sub.1-3 alkoxy substituted with one or more of --OH or (3) ##STR309## or pharmaceutically acceptable salt thereof.

4. The compound of claim 3 of the formula ##STR310## wherein V is absent

R.sup.1 is:

1) --C.sub.1-4 alkyl unsubstituted or substituted with one or more of

c) aryl unsubstituted or substituted with one or more of C.sub.1-4 alkyl, amino, hydroxy or aryl,

e) a 5-7 membered cycloalkyl group unsubstituted or substituted with one or more of

i) halo,

ii) C.sub.1-3 alkoxy, or

iii) aryl,

f) heterocycle, said heterocycle being piperidinyl, pyridyl, thienyl, pyrrolyl, thiazolyl, imidazolyl, furyl benzimidazolyl, pyrazinyl, isoxazolyl, pyridazinyl,or quinolinyl, said heterocycle unsubstituted or substituted with one or more of oxo, halo, C.sub.1-4 alkoxy, C.sub.1-4 alkyl; ##STR311## Boc, R.sup.3 is benzyl, unsubstituted or substituted with one or more of (1) hydroxy, (2) C.sub.1-3 alkoxy substituted with one or more of --OH or (3) ##STR312## or pharmaceutically acceptable salt thereof.

5. The compound of claim 4, of the formula ##STR313## wherein V is absent;

R .sup.1 is C.sub.1-4 alkyl substituted with pyridyl or aryl;

R.sup.3 is benzyl, unsubstituted or substituted with one or more of (1) hydroxy, (2) C.sub.1-3 alkoxy substituted with one or more of-OH or (3) ##STR314## or a pharmaceutically acceptable salt thereof.

6. The compound of the formula ##STR315## or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is selected from ##STR316##

7. A compound of the formula: ##STR317## or pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a compound according to claims 3, 4, 5 , or 6 and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8 for use in the treatment of AIDS, in the treatment of infection of HIV, or in the inhibition of HIV protease.

10. A pharmaceutical composition comprising the compound ##STR318## or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. A method of treating AIDS comprising administering to a mammal in need of such treatment an effective amount of a compound according to claims 5 or 7.

12. A method of treating infection by HIV comprising administering to a mammal in need of such treatment an effective amount of a compound according to claims 5 or 7.

13. A method of inhibiting HIV protease comprising administering to a mammal in need of such treatment an effective amount of a compound according to claims 5

HIV protease inhibitors

2008-01-07T07:23:00.000-08:00

Abstract

HIV protease inhibitors, obtainable by chemical synthesis, inhibit or block the biological activity of the HIV protease enzyme, causing the replication of the HIV virus to terminate. These compounds, as well as pharmaceutical compositions that contain these compounds and optionally other anti-viral agents as active ingredients, are suitable for treating patients or hosts infected with the HIV virus, which is known to cause AIDS.

Patent number: 5484926
Filing date: Feb 2, 1994
Issue date: Jan 16, 1996
Inventors: Bruce A. Dressman, James E. Fritz, Marlys Hammond, William J. Hornback, Stephen W. Kaldor, Vincent J. Kalish, John E. Munroe, Siegfried H. Reich, John H. Tatlock, Timothy A. Shepherd, Michael J. Rodriguez
Assignee: Agouron Pharmaceuticals, Inc.
Primary Examiner: D. Margaret M. Mach

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What is claimed is:

1. A compound of the formula ##STR136## or a prodrug thereof or a pharmaceutically acceptable salt thereof.

2. A stereoisomer of the compound according to claim 1, which has the formula ##STR137## or a prodrug thereof or pharmaceutically acceptable salt thereof.

3. An essentially pure salt according to claim 2.

4. An essentially pure stereoisomer according to claim 2.

5. A compound of the formula ##STR138##

6. A stereoisomer of the compound according to claim 5, which has the formula ##STR139##

7. An essentially pure stereoisomer according to claim 6.

8. An essentially pure prodrug according to claim 2.

Production of antibodies to HIV

2008-01-07T07:21:00.000-08:00

Patent number: 5019387
Filing date: Sep 8, 1987
Issue date: May 28, 1991
Inventors: Barton F. Haynes, Thomas J. Palker
Assignee: Duke University
Primary Examiner: Abdel A. Mohamed

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What is claimed is:

1. An essentially pure form of a hydrophilic peptide consisting essentially of an amino acid sequence of about 9 to 35 units in length and corresponding to at least one antigenic determinant of the envelope glycoprotein of human immunodeficiency virus (HIV) recognized by B lymphocytes, said peptide, when covalently linked to a carrier molecule, induces in a primate the production of high titers of antibodies that neutralize HIV.

2. The peptide according to claim 1, wherein said amino acid sequence corresponds to the SP-10 region of the envelope glycoprotein of HIV, or an antigenic portion thereof.

3. The peptide according to claim 2, wherein said amino acid sequence consists essentially of CTRPNNNTRKSIRIQRGpg, or an antigenic portion thereof.

4. An immunogenic conjugate that induces in a primate the production of high titers of antibodies that neutralize human immunodeficiency virus (HIV), said conjugate comprising a carrier molecule covalently attached to a hydrophilic peptide consisting essentially of an amino acid sequence of about 9 to 35 units in length and corresponding to at least the antigenic determinate of the envelope glycoprotein of HIV recognized by B lymphocytes.

5. The conjugate according to claim 4, wherein said carrier molecule comprises an amino acid sequence corresponding to a region of the envelope glycoprotein of HIV which region is distinct from said hydrophilic peptide and is recognized by T cells.

6. The conjugate according to claim 5, wherein said region is distinct from said hydrophilic peptic is T cell epitope T1 or T cell epitope T2, or an antigenic portion thereof.

7. The conjugate according to claim 4, wherein said carrier molecule is tetanus toxoid.

8. The conjugate according to claim 4, wherein said carrier molecule is covalently attached to said peptide through at least one spacer molecule.

9. The conjugate according to claim 8, wherein said spacer molecule consists of the dipeptide glycine-glycine.

10. The conjugate according to claim 4 wherein said peptide has an amino acid sequence corresponding to the SP-10 region of the envelope glycoprotein of HIV, or an antigenic portion thereof.

11. The conjugate according to claim 10 wherein said amino acid sequence consists essentially of CTRPNNNTRKSIRIQRGpg, or an antigenic portion thereof.

12. The conjugate according to claim 4, further comprising to the amino acid sequence FLGFLG which is covalently linked the C terminal of said peptide.

13. The conjugate according to claim 4 further comprising an amino acid sequence corresponding to a hypervariable region of the envelope protein of HIV isolates located C terminal to the SP-10 region of the envelope glycoprotein of HIV.

14. The conjugate according to claim 13 wherein said sequence corresponding to said hypervariable region is RAFVTIGKIGN and is directly linked to the C terminus of SP-10.

15. A method of producing immunity to HIV in a primate comprising administering to said primate at least one conjugate according to claim 4.

Check valve for urine collection device

2008-01-07T06:20:00.000-08:00

Abstract

A check valve between a catheter and a urine collection bag for an incontinent person must pass urine in the forward direction without significant head and must be free of back leakage to prevent infection. This valve has a rigid body so that the elastomeric sealing member mounted therein is not disturbed by the wearer's clothing. The sealing member has a pair of flat, parallel, normally spaced apart, sealing leaves integrally joined together along their lateral edges by webs to define a flat tube having a flat normally open passage therethrough. Means are provided for pressing on the lateral edges of the leaves for forcing the edges of the passage closed. The leaves are thin, soft elastomer, and the side edges are free to deflect laterally so that urine will pass forwardly through the valve in drop-wise fashion, and the valve can also handle appreciable flow rates. Back pressure on the valve urges it closed. Preferably the means holding the valves leaves together are clips...

Patent number: 3967645
Filing date: Jan 3, 1975
Issue date: Jul 6, 1976
Inventor: Roy Gregory
Assignee: Urocare Products, Inc.

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What is claimed is:

1. A liquid check valve having no back leakage and capable of draining substantially dry in the forward direction comprising:

a rigid body having a passage therethrough;

an elastomeric sealing member mounted within the body, said sealing comprising:

a pair of flat, parallel, normally spaced apart, sealing leaves;

a web among each lateral edge of the sealing leaves and integral therewith for joining the adjacent edges of the leaves together, said leaves and webs collectively defining a flat tube having a flat, normally open, passage therethrough; and

a peripheral end flange integral with the leaves for mounting the sealing member in the body; and

means for pressing on the lateral edges of the leaves for forcing the lateral edges of the flat passage closed, comprising spaced apart wall portions extending longitudinally in the rigid body for receiving the lateral edges of the sealing leaves, said wall portions being spaced apart no more than the thickness of the elastomer portion of the sealing member therebetween.

2. A liquid check valve having no back leakage and capable of draining substantially dry in the forward direction comprising:

a rigid body having a passage therethrough;

an elastomeric sealing member mounted within the body, said sealing member comprising:

a pair of flat, parallel, normally spaced apart, sealing leaves;

a web among each lateral edge of the sealing leaves and integral therewith for joining the adjacent edges of the leaves together, said leaves and web collectively defining a flat tube having a flat, normally open, passage therethrough; and

a peripheral end flange integral with the leaves for mounting the sealing member in the body;

a longitudinally extending lateral flange portion adjacent each web; and

means for pressing on the lateral edges of the leaves for forcing the lateral edges of the flat passage closed, comprising a slot in the body for receiving the flanged portion and having a width no more than the thickness of the elastomeric portion of the sealing member received within the slot.

3. A liquid check valve as defined in claim 2 wherein the flanged portion comprises a pair of flanges defining a T-shaped lateral edge along each lateral edge of the leaves, and wherein the longitudinal slot in the body has a T-shaped cross-section.

4. A liquid check valve as defined in claim 2 wherein the sealing member further comprises a longitudinally extending groove in a leaf adjacent the flange portion for reducing cross section of the respective leaf and reducing resistance to deflection.

5. A liquid check valve having no back leakage and capable of draining substantially dry in the forward direction comprising:

a rigid body having a passage therethrough;

an elastomeric sealing member mounted within the body, said sealing member comprising:

a peripheral end flange;

a pair of edge flanges extending downward from the end flange;

a pair of flat, parallel, normally spaced apart sealing leaves integral with the end flange wherein each leaf is relatively thinner nearer the peripheral end flange and relatively thicker remote from the end flange;

a hollow spherical membrane interconnecting the ends of the leaves nearer the end flange to the end flange; and

6. A liquid check valve having no back leakage and capable of draining substantially dry in the forward direction comprising:

a rigid body having therethrough;

an elastomeric sealing member mounted within the body, said sealing member comprising:

a pair of flat, parallel, normally spaced apart, sealing leaves;

a peripheral end flange integral with the leaves for mounting the sealing member in the body; and

a generally U-shaped rigid clip along each lateral edge of the leaves for forcing the edges of the leaves together, and hence closing the normally open passage, said clips being separate from the rigid body and from each other.

7. A liquid check valve as defined in claim 6 further comprising a T-shaped flange portion along each lateral edge of the leaves overlapping the web and an edge portion of the normally open passage, each U-shaped clip compressing the T-shaped flange portion and closing an edge of the normally open passage.

8. A liquid check valve as defined in claim 7 wherein the passage has tapered or feathered lateral edges without any sharp corners.

9. A liquid check valve as defined in claim 6 wherein each clip includes a relief groove adjacent the web for accommodating bulging of the sealing member upon compression of the flange portion.

10. A liquid check valve as defined in claim 6 wherein each leaf is relatively thinner at the end nearer the end flange and relatively thicker at the end remote therefrom.

11. In an elastomeric sealing member for a urine check valve comprising a pair of flat, parallel, normally spaced apart, sealing leaves; a web along each lateral edge of the sealing leaves and integral therewith for joining the adjacent edges of the leaves together, said leaves and webs collectively defining a flat tube having a flat passage therethrough; a peripheral flange at one end for mounting the sealing member; and a funnel-like section integral with the flange and leaves for forming a transition therebetween,

the improvement wherein the flat passage between the leaves is normally open with the leaves spaced apart a small distance, and wherein each leaf is relatively thinner adjacent the funnel-like section and relatively thicker at the end remote therefrom, and the faces of the leaves defining the flat passage are uniformly spaced apart through the length of the passage.

12. In an elastomeric sealing member for a urine check valve comprising a pair of flat, parallel, normally spaced apart, sealing leaves; a web along each lateral edge of the sealing leaves and integral therewith for joining the adjacent edges of the leaves together, said leaves and webs collectively defining a flat tube having a flat passage therethrough; a peripheral flange at one end for mounting the sealing member; and a funnel-like section integral with the flange, and leaves for forming a transition therebetween,

the improvement wherein the flat passage between the leaves is normally open with the leaves spaced apart a small distance, and there is a generally U-shaped rigid clip along each edge of the leaves, the sides of each U-shaped clip being spaced apart no more than the thickness of the elastomeric material therebetween for forcing the edges of the normally open passage closed.

13. In a combination as defined in claim 12 the further improvement wherein each clip further comprises a relief groove adjacent the web for accommodating bulging of the sealing member upon closing of the edges of the normally open passage.

14. In an elastomeric sealing member for a urine check valve comprising a pair of flat, normally spaced apart, sealing leaves; a web along each lateral edge of the sealing leaves and integral therewith for joining the adjacent edges of the leaves together, said leaves and webs collectively defining a flat tube having a flat passage therethrough; a peripheral flange at one end for mounting the sealing member; and a funnel-like section integral with the flange and leaves for forming a transition therebetween,

the improvement wherein the flat passage between the leaves is normally open with the leaves spaced apart a small distance and wherein the leaves are substantially continuously tapered in thickness with the thinner part adjacent the funnel-like section.

Device for collecting and absorbing urine

2008-01-07T06:18:00.000-08:00

Abstract

A device for collecting and absorbing urine, comprising a laminate composed of several layers, in which an outer plastic casing in combination with a material permeable to urine form a space enclosing an absorption body. The absorption body includes at least one super-absorbent laminate which may be a tissue integrated with a super-absorbent polymer and which upon absorption forms a gel. The space surrounding the absorption body is designed to permit expansion when the absorption body assumes the gel phase.

Patent number: 4886509
Filing date: Feb 11, 1988
Issue date: Dec 12, 1989
Inventor: Lars Mattsson
Primary Examiner: Sharon Rose

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What is claimed is:

1. A device for collecting and absorbing urine, comprising:

a laminate having a plurality of layers including a layer of outer plastic casing and a layer of material permeable to urine connected to said layer of plastic casing by sealing along the peripheral edges of each layer, said sealing forming an outer seam contour along the top, bottom and sides of the device;

said sealing defining an expandable space comprising the interior of the laminate;

an absorption body located in the expandable space comprising tissue integrated with a super-absorbent polymer which upon absorption expands to form a gel;

said absorption body being narrower than said laminate and located centrally within said laminate such that the difference between the outer seam contour and the absorption body forms outer flaps along the sides of the laminate;

said laminate being folded a first time transversely to said outer flaps approximately near the center of said laminate so that the side edges of said laminate are in contact and the outer flaps overlap themselves in parallel; said side edges of said laminate being sealed together where they contact forming a pocket;

said outer flaps being folded over the absorption body at an angle with respect to the outer seam contour of the device; and

a patch of releasable adhesive located between the outer flaps and the main absorption body for adhering the outer flaps to the main absorption body prior to said absorption and for releasing said outer flaps from said absorption body when the absorption body assumes the gel phase, said released outer flaps automatically unfolding to achieve an expansion of the pocket.

2. The device of claim 1, further comprising a spillage insert located in said pocket.

3. A device for collecting and absorbing urine according to claim 1, wherein said patch of adhesive is an elongated vertically orientated patch of adhesive.

4. A device for collecting and absorbing urine according to claim 3, wherein said elongated vertically orientated patch of adhesive is located near the outer seam contour at the top of the device.

5. A device according to claim 4, comprising a layer of porous structure arranged substantially over the absorption body to mechanically spread the urine across the absorption body, the layer of porous structure comprising a substantially elastic, non- absorbent material, preferably a foam plastic, having open cells.

Respiratory control system and apparatus

2008-01-07T06:16:00.000-08:00

Abstract

A respiratory control system and apparatus for delivering controlled and or assisted respiratory cycles to the patient includes a flow and pressure control valve, exhalation valve, flow transducer, pressure transducer, and a central control unit that servo controls the flow and pressure valve and the exhalation valve based upon the flow and pressure signals from transducers and control panel. The cycles are initiated by detection of inspiratory effort or in accordance to other criteria, maintaining simultaneously the inspired flow and pressure in the airway at or above a predetermined controlled flow and controlled pressure until the delivery of a predetermined controlled volume, and also extending the maintenance of the controlled pressure by a predetermined period of time after the instant in which the volume was completed, and beyond this period until the delivered flow has decreased until a minimum flow threshold level.

Patent number: 5582163
Filing date: Dec 14, 1993
Issue date: Dec 10, 1996
Inventor: Jorge Bonassa
Assignee: Intermed Equipamento Medico Hospitalar Ltda.

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What is claimed is:

1. A method for delivering a controlled volume of breathable gas to a patient to improve synchronism between patient effort and system flow demand while assuring desired minimum requirements for airway pressure, flowrate and volume, the method comprising:

providing a respiratory circuit including an inspiratory tube, expiratory tube, exhalation valve and flow/pressure valve;

monitoring airway pressure at airway entry of a patient;

initiating breathable gas volume delivery to a patient's airway at the trigger instant upon detection of an inhalation attempt by a patient which is sufficient to lower airway pressure to a reference trigger pressure;

at trigger instant, opening the flow pressure valve to deliver desired controlled flowrate through said inspiratory tube of said respiratory circuit, at the same time closing the end of the expiratory tube of the respiratory circuit using the exhalation valve and maintaining the respiratory circuit closed during inhalation up to a maximum acceptable airway pressure;

beginning to monitor at trigger instant, the flowrate and delivered volume of breathable gas during inhalation by a patient, said step of monitoring continuing throughout a respiratory cycle;

continuing to deliver breathable gas to patient by the flow/pressure valve, comparing actual airway pressure monitored at airway entry of the patient with the desired controlled pressure;

if patient monitored airway is below desired controlled pressure, continuing to deliver breathable gas to patient, increasing flowrate at airways above desired controlled flowrate, based upon the difference of monitored air pressure and desired controlled pressure, to null existing pressure differences, said step of delivering continuing throughout inspiratory portion of the respiratory cycle, until delivered volume reaches desired controlled volume;

if patient monitored airway pressure is above desired controlled pressure, continuing to deliver breathable gas to the patient, maintaining desired controlled flowrate at airways, said step of delivering continuing throughout inspiratory portion of the respiratory cycle, until delivered volume reaches desired controlled volume; and

at the volume completion instant in which the delivered volume reaches desired controlled volume, terminating the delivery of the controlled volume of breathable gas to patient by closing flow/pressure valve thus decreasing the flowrate through said inspiratory tube of said respiratory circuit to zero, opening the exhalation valve so as to permit such a patient to exhale the delivered volume and thus decreasing airway pressure to a predetermined positive and expiratory pressure.

2. A method as claimed in claim 1 further comprising:

extending inhalation beyond volume completion instant by a desired inspiratory hold time, maintaining inspiratory phase of respiratory cycle until desired inspiratory hold time elapses;

during said inspiratory hold time period, if patient monitored airway pressure is below desired controlled pressure, continuing to deliver breathable gas to the patient, controlling flowrate at airways based solely upon the difference of monitored air pressure and desired controlled pressure, to null existing pressure difference, said step of delivering continuing throughout inspiratory hold time portion of the respiratory cycle, until inspiratory hold time has elapsed;

during said inspiratory hold time period, if patient monitored airway pressure is above desired controlled pressure, opening in a controlled manner the exhalation valve based upon the difference between the desired controlled pressure and monitored airway pressure, to null existing pressure differences, said step of delivering continuing throughout inspiratory hold time portion of the respiratory cycle, until inspiratory hold time elapses; and

at the instant in which inspiratory hold time elapses, terminating the delivery of the controlled volume of breathable gas to patient by closing flow/pressure valve thus decreasing the flowrate through said inspiratory tube of said respiratory circuit to zero, opening the exhalation valve so as to permit such a patient to exhale the delivered volume and thus decreasing airway pressure to a predetermined positive and expiratory pressure.

3. A method as claimed in claim 1 further comprising:

extending inhalation beyond the volume completion instant by an additional flow supplementation period, maintaining inspiratory phase of respiratory cycle until the flowrate through said inspiratory tube of said respiratory circuit decreases to a predetermined minimum flowrate threshold;

during said additional flow supplementation period, if patient monitored airway pressure is below desired controlled pressure, continuing to deliver breathable gas to the patient, controlling flowrate at airways based solely upon the difference of monitored air pressure and desired controlled pressure, to null existing pressure difference, said step of delivering continuing throughout additional period, until the flowrate decreases to a predetermined minimum flowrate threshold; and

at the instant in which flowrate decreases to predetermined minimum flowrate threshold, terminating the delivery of the controlled volume of breathable gas to patient by closing flow/pressure valve thus decreasing the flowrate through said inspiratory tube of said respiratory circuit to zero, opening the exhalation valve so as to permit such a patient to exhale the delivered volume and thus decreasing airway pressure to a predetermined positive and expiratory pressure.

4. A method as claimed in claim 3 in which the value of minimum flowrate threshold that terminates the breathable gas volume delivery to a patient is determined as a percentage of the maximum flowrate monitored during the initiation of inhalation.

5. A method as claimed in claim 1, in which the desired controlled flowrate is a predetermined constant value.

6. A method as claimed in claim 1 in which the desired controlled pressure is a predetermined constant value.

7. A method as claimed in claim 1 in which the desired controlled flowrate is the ratio of desired controlled volume and a desired inspiratory time.

8. A method as claimed in claim 1 in which the desired controlled flowrate is determined during first steps of inhalation based upon a predetermined equation until the difference between monitored airway pressure and desired controlled pressure diminishes to a predetermined value.

9. A method as claimed in claim 1 in which the desired controlled flowrate is a time dependent mathematical function, representing predetermined waveform.

10. A method as claimed in claim 1 in which the desired control flowrate is determined based upon the difference between monitored airway pressure and desired controlled pressure and the rate of change of monitored airway pressure between predetermined time period steps.

11. A method as claimed in claim 1 in which the desired controlled flowrate is determined and continuously updated at predetermined time steps since the initiation of inhalation, computing at every instant the remainder of the volume to complete desired controlled volume (desired controlled volume subtracted from delivered volume at given instant) and the remainder of the inspiratory time (desired controlled inspiratory time subtracted from period of time since initiation of inhalation), and obtaining the instantaneous desired controlled flowrate by the ratio of the remainder of the volume and the remainder of the inspiratory time.

12. A method as claimed in claim 1 in which the desired controlled pressure is determined and continuously updated after a predetermined number of respiratory cycles, as a direct proportion of the average mean delivered flowrate.

13. A method as claimed in claim 1 in which the desired controlled pressure is determined and continuously updated after a predetermined number of respiratory cycles, based upon the patient's respiratory system impedance, determined by any means.

14. A method as claimed in claim 1 in which the predetermined positive end expiratory pressure reached during exhalation is zero.

15. A method as claimed in claim 1 in which the breathable gas volume delivery is automatically initiated based upon a desired respiratory rate.

16. A method as claimed in claim 1 in which the breathable gas volume delivery is automatically initiated upon the detection of the occurrence of a patient's apnea period which is longer than a desired maximum allowable apnea interval.

17. A method as claimed in claim 1 in which the breathable gas volume delivery is automatically initiated upon the detection of the occurrence of a decrease on monitored minute volume, comprising the summation of the volume delivered in every inhalation during the last minute, which is lower than a desire minimum allowable minute volume.

Patient respiratory system drug applicator

2008-01-07T06:15:00.000-08:00

Abstract

A respiratory system drug applicator for a patient is disclosed which may include a number of features to enhance the administration of the aerosolized drug to the patient. For instance, an adjustable flow regulator may be utilized which regulates the air flow during inhalation by the patient (during which the aerosolized drug is also administered to the patient's respiratory system), and thus affects the patient's breathing pattern. Moreover, a distensible drug reservoir which changes shape during inhalation and exhalation by the patient may be utilized. This may be used to provide biofeedback to the patient regarding the patient's breathing pattern.

Patent number: 5613489
Filing date: Dec 7, 1994
Issue date: Mar 25, 1997
Inventors: Warren C. Miller, Robert J. McKinnon
Assignee: Westmed, Inc.
Primary Examiner: William J. Deane, Jr.

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What is claimed is:

1. A patient respiratory system drug applicator, comprising:

a drug dispenser;

a patient inhalator;

a first conduit fluidly interconnecting said drug dispenser and said patient inhalator and comprising first and second ports, said drug dispenser being interconnected with said first port and said second port fluidly interconnecting said patient inhalator with an oxygen source;

a distensible drug reservoir fluidly interconnected with said patient inhalator; and

an adjustable flow regulator associated with said second port, wherein said adjustable flow regulator allows for an adjustment of an amount of a flow provided to the patient which is from said oxygen source and thereby also an adjustment of an amount of said flow provided to the patient which is from said distensible drug reservoir, whereby said adjustable flow regulator may be used to establish a certain pulsation of said distensible drug reservior, due to patient inhalations and exhalations, which provides biofeedback to the patient regarding the patient's breathing pattern and thereby the respiratory administration of the drug to the patient.

2. A drug applicator, as claimed in claim 1, wherein:

said drug dispenser comprises a nebulizer.

3. A drug applicator, as claimed in claim 1, wherein:

said first conduit is substantially axially extending and comprises first and second ends and a sidewall, said patient inhalator being interconnected with said first end of said first conduit in axial alignment with said first conduit, and wherein said first port is positioned on said sidewall.

4. A drug applicator, as claimed in claim 3, wherein:

said second port is on said sidewall axially displaced from and substantially perpendicular to said first port.

5. A drug applicator, as claimed in claim 4, wherein:

said distensible drug reservoir is interconnected with said second end of said first conduit.

6. A drug applicator, as claimed in claim 1, wherein:

said adjustable flow regulator comprises an orifice and a valve movable between first and second positions to change a size of said orifice, wherein a cross-sectional area of said orifice taken perpendicularly to a flowpath through said orifice with said valve in said first position is no more than about 0.3 square inches and wherein said cross-sectional area of said orifice with said valve in said second position is less than said cross-sectional area of said orifice with said valve in said first position.

7. A drug applicator, as claimed in claim 6, wherein:

said cross-sectional area of said orifice with said valve in said first position is no more than about 0.1 square inches.

8. A drug applicator, as claimed in claim 7, wherein:

said cross-sectional area of said orifice with said valve in said second position is at least about 0.02 square inches.

9. A drug applicator, as claimed in claim 1, wherein:

said patient inhalator interfaces with said first conduit on a first side of first port and wherein said drug reservoir interfaces with said first conduit on a second side of said first port.

10. A method for administering an aerosolized drug to a patient's respiratory system utilizing a distensible drug reservoir fluidly connected to the patient, comprising the steps of:

inhaling oxygen by the patient from an outside source;

providing the aerosolized drug to the patient during said inhaling step from at least the distensible drug reservior;

exhaling by the patient after said inhaling step;

monitoring a degree of said inhaling step, said monitoring step comprising preserving a changing shape of the distensible drug reservior during said inhaling and exhaling steps, wherein said observing step provides biofeedback to the patient regarding the patient's breathing pattern and thereby the respiratory administration of the aerosolized drug to the patient;

controlling an oxygen flow condition for said inhaling step, wherein said controlling step comprising providing a resistance between the outside source and the patient;

adjusting the resistance based upon said observing step, wherein said adjusting step provides an adjustment of an amount of a flow provided to the patient which is from said oxygen source and thereby also an adjustment of an amount of said flow provided to the patient which is from said distensible drug reservior, whereby said adjusting step is used to establish a certain pulsation of said distensible drug reservoir, due to patient inhalations and exhalations, which provides biofeedback to the patient regarding the patient's breathing pattern and thereby the respiratory administration of drug to the patient; and

repeating said inhaling, providing, exhaling and monitoring steps a plurality of times.

11. A method, as claimed in claim 10, wherein:

said providing step comprises nebulizing the drug.

12. A method, as claimed in claim 10, wherein:

the drug reservoir has a first gas volume of the aerosolized drug in one of the inhaling steps and a second gas volume of the aerosolized drug in a subsequent exhaling step, the second volume being greater than the first volume and providing an observable difference in the shape of the drug reservoir.

13. A method, as claimed in claim 10, further comprising the step of:

changing a degree of said inhaling step based upon said observing step.

14. A method, as claimed in claim 10, further comprising the step of:

producing a greater degree of difference in the change in the shape of the distensible drug reservoir based upon said observing step.

Respiratory support system and suction catheter device

2008-01-07T06:12:00.000-08:00

Abstract

A suction catheter device usable with a respiratory support system which includes a catheter enveloped in a sleeve having a proximal end connector for connection to a suction source through a suction control device such as a suction control valve, and a distal end connector for attachment to a manifold of the respiratory support system. The proximal end connector includes a normally closed valve therein which prevents air flow through the catheter until a suction control device is attached thereto. The proximal end connector may also be adapted for use on a dual lumen catheter and thereby include a fluid injection passage having a one-way check valve therein. The distal end connector of the suction catheter device includes a magnifying window through which a portion of the catheter within the connector can be viewed. The catheter includes one or more markings thereon which indicate the relative position of the catheter and the connector, and which can be viewed through the magnifyi...

Patent number: 5309902
Filing date: Oct 19, 1992
Issue date: May 10, 1994
Inventors: Kok-Hiong Kee, James G. Schneider, Neal G. Koller, Robert H. Bruno
Assignee: Sherwood Medical Company
Primary Examiner: Eric P. Raciti

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What is claimed is:

1. A respiratory support system comprising:

a ventilator manifold adapted to be connected for fluid flow attachment between a patient and a ventilator circuit,

a sleeved suction catheter device including a catheter, a distal end connector and a proximal end connector, and

a suction control valve,

said distal end connector being adapted for connection with said ventilator manifold and said proximal end connector being adapted for connection with said suction control valve, and

a normally closed catheter valve in said proximal end connector of said sleeved catheter device, said normally closed catheter valve being operative between a normally closed sealing position and an open operative position, said normally closed catheter valve preventing fluid flow through said catheter in sid closed sealing position and allowing fluid flow through said catheter in said open operative position,

means responsive to attachment of said suction control valve to said proximal end connector to move said normally closed catheter valve from said sealing position to said open operative position.

2. A respiratory support system according to claim 1 wherein said ventilator manifold further includes an accessory access port for allowing attachment of said distal end connector of said sleeved catheter device to said ventilator manifold, said accessory access port being normally closed against fluid flow therethrough,

whereby attachment of said distal end connector of said sleeved catheter device to said accessory access port operates to open said accessory access port to allow fluid flow access between sid ventilator manifold and said catheter.

3. A respiratory support system according to claim 2 wherein said accessory access port includes a normally closed access port valve therein said normally closed access port valve being operative between a normally closed sealing position and an open operative position.

whereby, said normally closed access port valve is forced from said normally closed sealing position to said open operative position by said distal end connector to allow fluid flow through said accessory access port.

4. A respiratory support system according to claim 2 wherein said distal end connector includes an adaptor formed of a generally hollow tubular member having a proximal end and a distal end, said proximal end of said adaptor being formed as part of said distal end connector and said distal end of said adaptor operating to open said normally closed access port valve to said open operative position when inserted into said accessory access port.

5. A respiratory support system according to claim 4 wherein said accessory access port further includes an injection fluid inlet opening therein and said adaptor includes an injection fluid opening therethrough,

whereby, when said adaptor is positioned for operation in said accessory access port of said ventilator manifold, said injection fluid inlet opening is aligned with said injection fluid opening of said adaptor whereby, fluid can be injected through said injection fluid inlet opening and said injection fluid opening into said adaptor.

6. A respiratory support system according to claim 5 wherein said distal end connector further includes a locking device which operates in conjunction with said injection fluid inlet opening of said ventilator manifold to lock said adaptor in a single relative orientation with said accessory access port in which said injection fluid inlet opening of said accessory access port is aligned with said injection fluid opening of said adaptor.

Device for stimulating human respiratory system

2008-01-07T05:58:00.000-08:00

Abstract

A device for stimulating the human respiratory system by making breathing more difficult and limiting lung ventilation. The device comprises a mouth-piece for insertion in the mouth of a person, or a mask attachable to the face of this person. The mouth-piece or mask has a central opening through which the person may breathe. A tubular body defining an air duct is connected at one end to the mouth-piece or to the mask with the air duct in alignment and communication with the opening. The device also comprises a membrane mounted in the tubular body at the other end thereof to put up a breathing resistance in at least one respiratory direction. Proper stimulation is obtained when use is made of a tubular body long enough to increase the dead space of the respiratory system of the person using the device.

Patent number: 4601465
Filing date: Mar 22, 1984
Issue date: Jul 22, 1986
Inventor: Jean-Yves Roy
Primary Examiner: Kathleen D'Arrigo

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What is claimed is:

1. A device for simulating the human respiratory system by making breathing more difficult and limiting lung ventilation, said device comprising:

a mouth-piece for insertion in the mouth of a person, said mouth-piece having a central opening through which the person may breathe,

a tubular body defining an air duct, said tubular body being connected at one end to the mouth-piece with the air duct in alignment and communication with the opening of said mouth-piece, and

obstruction means mounted in the tubular body at the other end thereof to put up a breathing resistance in both the inspiratory and expiratory directions, said mouth-piece, tubular body and obstruction means being very compact in size and light enough to be carried exclusively through the mouth-piece when the same is inserted in the mouth of the person, said tubular body further being long enough to increase the dead space of the respiratory system of the person using the device,

wherein:

the air duct at the end of the tubular body opposite to the mouth-piece is divided into two parallel separate passages;

the obstruction means is mounted in only one of said passages and consists of a membrane permeable to air;

said obstruction means also comprises means to make it detachable and removable;

a check valve is mounted in the other passage to allow air to be freely breathed in at least one of the respiratory direction, said check valve comprising: means to make it detachable and reversible, thereby permitting selection of the direction in which air is allowed to be freely breathed in the passage in which said check valve is mounted.

2. A device for stimulating the human respiratory system by making breathing more difficult and limiting lung ventilation, said device comprising:

a mouth-piece for insertion in the mouth of a person, said mouth-piece having a central opening through which the person may breathe,

a tubular body defining an air duct, said tubular body connected at one end to the mouth-piece with the air duct in alignment and communication with the opening of said mouth-piece, and

wherein:

the air duct at the end of the tubular body opposite to the mouth-piece is divided into two parallel separate passages;

the obstruction means is mounted in only one of said passages and consists of an impermeable membrane provided with a central hole having a diameter smaller than the diameter of the passage in which said membrane is mounted

said obstruction means also comprises means to make it detachable and removable;

3. A device for stimulating the human respiratory system by making breathing more difficult and limiting lung ventilation said device comprising:

a mouth-piece for insertion in the mouth of a person, said mouth-piece for insertion in the mouth of a person, said mouth-piece having a central opening through which the person may breathe,

a tubular body defining an air duct, said tubular body being connected at one end to the mouth-piece with the air duct in alignment and communication with the opening of said mouth-piece, and

obstruction means mounted in the tubular body at the other end thereof to put up a breathing resistance in at least one respiratory direction, said mouth-piece, tubular body and obstruction means being very compact in size and light enough to be carried exclusively through the mouth-piece when the same is inserted in the mouth of the person, said tubular body further being long enough to increase the dead space of the respiratory system of the person using the device, wherein said obstruction means at the other end of the tubular body comprises:

a rigid membrane permeable to air, said membrane extending transversally across a portion of the air duct and providing a rigid edge transversal to said air duct; and

a flexible membrane transversally mounted across the air duct, said flexible membrane covering the portion of said air duct not covered by the rigid membrane and overlapping at least part of the rigid membrane close to its rigid edge to form with said rigid membrane a check valve; whereby air is allowed to be freely breathed through this check valve in one respiratory direction while it is subject to breathing resistance through the rigid membrane in the other direction.

4. The device of claim 3, wherein the flexible membrane is also permeable to air.

5. The device of claim 4, wherein both membranes are fixed onto a same ring detachably mounted in a reversible manner in the tubular body.

Prosthetic ring for heart surgery

2008-01-03T00:19:00.000-08:00

Abstract

A prosthetic ring includes a core enclosed in a textile sheath, the sheath being sutured to the heart or the aorta of a patient. The core includes at least one relatively rigid portion and one portion that is relatively flexible compared to the rigid portion. The cross-sectional diameter of the core varies along the circumference of the ring, decreasing from a maximum at the rigid portion to a minimum at the flexible portion, giving the ring sufficient flexibility to accommodate heart wall movement.

Patent number: 5607471
Filing date: Aug 21, 1995
Issue date: Mar 4, 1997
Inventors: Jacques Seguin, Robert Rogier
Assignee: Jacques Seguin

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What is claimed is:

1. A prosthetic ring for at least one of mitral, tricuspid and aortic annuloplasty, comprising a core enclosed in a textile sheath, wherein:

the sheath comprises a suturing means;

the core is formed from a single material, the core comprises at least one relatively rigid portion and at least one flexible portion that is flexible relative to the rigid portion; and

a cross-sectional area of the core varies along a circumference of the ring, the area decreasing from the rigid portion toward the flexible portion, allowing deformation of the ring in all planes passing through the ring.

2. The prosthetic ring of claim 1, wherein at least one of a thickness and a height of the core decreases as the core area decreases.

3. The prosthetic ring of claim 1, wherein the cross-sectional area of the core decreases asymmetrically with respect to a center of the core.

4. The prosthetic ring of claim 1, wherein the cross-sectional area of the core decreases symmetrically with respect to a center of the core.

5. The prosthetic ring of claim 1, wherein the cross-sectional area of the core is stepped along the circumference of the ring.

6. The prosthetic ring of claim 1, wherein the cross-sectional area of the core is smooth along the circumference of the ring.

7. The prosthetic ring of claim 1, wherein the core is formed by molding a synthetic material.

8. The prosthetic ring of claim 7, wherein the synthetic material is a linear polyoxymethylene acetal resin.

9. The prosthetic ring of claim 1, wherein the core is formed of a titanium alloy.

10. The prosthetic ring of claim 1, wherein the core is assembled of at least two segments of material, one of the segments including the rigid portion of the core and another of the segments including the flexible portion of the core.

11. The prosthetic ring of claim 1, wherein the flexible portion of the core is reinforced by an insert of elastomeric material.

12. The prosthetic ring of claim 1, comprising a radiopaque element.

13. A ring intended for mitral annuloplasty, comprising:

a sheath; and

a core enclosed in the sheath;

wherein the core has a shape generally in the form of a "D", the core is formed from a single piece of synthetic material and comprises a relatively rigid portion and a flexible portion, wherein the flexible portion is flexible relative to the rigid portion;

the flexible portion is essentially opposite the rigid portion; and

a cross-sectional area of the core varies from a maximum area at the stiffest portion of the core to a minimum area located essentially opposite a median part of the stiffest portion of the core.

14. A ring intended for tricuspid annuloplasty, comprising:

a sheath; and

a core enclosed in the sheath;

wherein the core has an essentially ovoid shape, the core is formed from a single piece of synthetic material and comprises a relatively rigid portion and a flexible portion, wherein the flexible portion is flexible relative to the rigid portion;

the flexible portion is situated essentially opposite the rigid portion; and

a cross-sectional area of the core varies from a maximum area at the stiffest portion of the core to a minimum area located essentially opposite a median part of the stiffest portion of the core.

15. A ring intended for aortic annuloplasty, comprising

a sheath; and

a core enclosed in the sheath;

wherein the core is formed from a single piece of synthetic material and the core includes three curved portions connected to each other by commissures substantially perpendicular to a plane of the ring;

each curved portion comprising a relatively rigid portion and a flexible portion, wherein the flexible portion is flexible relative to the rigid portion; and

a cross-sectional area of the core changes along the ring, the cross-sectional area is minimal at a median part of each of the curved portions, the median part of each curved portion forms the flexible portion, and the cross-sectional area increases in the direction of the commissures forming the rigid portion.

16. A prosthetic ring for at least one of mitral, tricuspid and aortic annuloplasty, comprising a core enclosed in a textile sheath, wherein:

the sheath comprises a suturing means;

the core is integrally formed of one piece, the core comprises at least one relatively rigid portion and at least one flexible portion that is flexible relative to the rigid portion; and

Retracting heart tissue in closed-chest heart surgery using endo-scopic retraction

2008-01-03T00:14:00.000-08:00

Abstract

The invention provides a system and method for manipulating a tissue structure within a body cavity. In a preferred embodiment, the invention provides a system and method for retracting and supporting the heart wall to provide access into the heart during a cardiac surgical procedure. The system comprises a tissue supporting member (500) positionable through a first percutaneous intercostal penetration into the thoracic cavity. The tissue supporting member has a contact surface (502) configured for supporting a portion of the heart wall. A retractor (40a) includes a shaft (400) with a proximal end, a distal end configured for introduction through a second percutaneous penetration and a diameter less than the width and length of the contact surface. A hook (428) is slidably coupled to the distal end of the shaft for releasably holding the tissue supporting member such that the contact surface is arranged transversely to the longitudinal axis of the shaft. With this configuration,...

Patent number: 5613937
Filing date: Aug 23, 1994
Issue date: Mar 25, 1997
Inventors: Michi E. Garrison, Sean C. Daniel
Assignee: Heartport, Inc.
Primary Examiner: Beverly M. Flanagan

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What is claimed is:

1. A method of retracting an incised opening in a wall of a chamber in a patient's heart, the method comprising the steps of:

introducing a tissue supporting member, releasably connected directly to an introducer, into the patient's thoracic cavity through a first percutaneous intercostal penetration, within a first intercostal space between two adjacent ribs, the tissue supporting member having a contact surface with a first length and a first width;

introducing a shaft having a longitudinal axis through a second percutaneous intercostal penetration, within a second intercostal space between two adjacent ribs, the shaft having a diameter smaller than the first width and the first length;

coupling the tissue supporting member to the shaft within the patient's thoracic cavity while holding the tissue supporting member with the introducer;

positioning the tissue supporting member within an incised opening in a chamber wall of the patient's heart;

manipulating said shaft from outside the patient's chest to position the contact surface of the tissue support member into supportive contact with the chamber wall; and

applying a force to the shaft to retract the chamber wall thereby enlarging the opening.

2. The method of claim 1 wherein the tissue supporting member introducing step is carried out with the first percutaneous intercostal penetration being created in a right lateral side of the patient's chest.

3. The method of claim 1 wherein the shaft introducing step is carried out with the second percutaneous intercostal penetration being created in an anterior portion of the patient's chest.

4. The method of claim 1 wherein the applying step is carried out with the chamber wall being retracted anteriorly.

5. The method of claim 1 wherein the tissue supporting member introducing step is carried out with the tissue supporting member being introduced through a cannula positioned in the first percutaneous intercostal penetration.

6. The method of claim 1 further comprising the step of viewing the patient's heart through a scope extending through a third percutaneous intercostal penetration in the patient's chest.

7. The method of claim 1 further comprising the step of:

introducing an instrument through the first percutaneous intercostal penetration and through the opening; and

performing a procedure on the patient's heart with the instrument.

8. The method of claim 7 wherein the performing step is a valve replacement.

9. The method of claim 8 wherein the performing step is a mitral valve replacement.

10. The method of claim 7 wherein the opening is in a left atrium of the patient's heart.

11. The method of claim 10 wherein the tissue supporting member introducing step is carried out with the supporting member having said first length of sufficient length to extend into the left atrium to engage the interatrial septum.

12. The method of claim 1 wherein the tissue supporting member introducing step is carried out with the tissue supporting member being introduced through the first percutaneous penetration by a second shaft, the second shaft having means at a distal end for releasably holding the tissue supporting member.

13. The method of claim 12 further comprising the step of: releasing the tissue supporting member from the second shaft after connecting the tissue supporting member to the first shaft.

14. The method of claim 1 further including the step of, before the tissue supporting member introducing step, arresting the heart.

15. The method of claim 14 further including the step of, before the arresting step, establishing cardiopulmonary bypass.

16. The method of claim 1 wherein said contact surface of said tissue support member generally extends in a direction away from the longitudinal axis of said shaft.

17. The method of claim 16 wherein said coupling step is accomplished by connecting said shaft to one end of said tissue support member.

18. The method of claim 17 wherein said positioning step includes the step of inserting an opposite second end of said tissue support member into the incised opening of the left atrium until a first lip portion thereof, extending rearwardly from said contact surface, supportably engages the interatrial septum.

19. The method of claim 18 wherein the contact surface of the tissue support member extends continuously between said first end and said second end.

20. The method of claim 19 wherein the contact surface has a curvature selected to conform to the inner surface of the incised opening.

21. The method of claim 1 wherein the tissue support member introducing step and the shaft introducing step are performed at generally right angles relative one another.

Cystotome for eye surgery

2008-01-02T03:47:00.000-08:00

Abstract

A cystotome for producing a continuous series of perforations in the anterior lens capsule of a human eye preparatory to cortex removal in extracapsular cataract extraction has a rectilinearly reciprocable, essentially poniard-shaped cutter for piercing the capsule while it is held taut along the base of an indentation pressed into the capsule such that the cutter moves into and out of a tubular support therefor along a path which is perpendicular to the base of the indentation, the movement of the cystotome along the capsule taking place only while it is out of engagement with the capsule with the cutter fully retracted.

Patent number: 4570632
Filing date: Mar 16, 1984
Issue date: Feb 18, 1986
Inventor: Randall L. Woods

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What is claimed is:

1. In the surgical art of extracapsular cataract extraction, a cystotome for incising a continuous series of perforations in the anterior lens capsule of a human eye preparatory to removal of a portion of said anterior lens capsule within the confines of said perforations to provide a cataract clearance opening in said anterior lens capsule, said cystotome comprising:

an elongated tube having a lateral extension at one end thereof terminating in a flat, continuous, outermost surface adapted to be held by the surgeon flatly against said anterior lens capsule;

a flexible shaft in said tube and reciprocable along the longitudinal axis thereof;

a cutter on one end of the shaft and disposed for relatively short, repetitive strokes into and out of the extension beyond said surface during reciprocation of said shaft;

means for reciprocating the shaft,

said cutter being a relatively short, essentially poniard-shaped, triangular instrument having keenly sharpened edges coverging toward an outermost, sharp point for stabbing the capsule to present a smooth, sharp slice in absence of tearing.

2. The invention of claim 1, said extension confining the cutter to rectilinear reciprocation into and out of the extension.

Performing eye surgery, methods and instrument

2008-01-02T03:39:00.000-08:00

Abstract

An instrument for surgically removing a lens from the eye comprising a housing that supports electrodes for bipolar cutting and splitting the nucleus of the lens.

Patent number: 5217459
Filing date: Aug 27, 1991
Issue date: Jun 8, 1993
Inventor: William Kamerling
Primary Examiner: S. C. Harris

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What is claimed is:

1. An instrument for surgical removal of the lens from the eye comprising

a support, said support including an elongated, hollow housing that has a stiff, flexible annular wall,

means for cutting a groove in the nucleus of the lens with bipolar electrical energy and splitting the nucleus at the groove, said last named means comprising energizable first and second electrodes that are carried by said support, said electrodes including distal ends that are operative when energized to generate a tissue cutting electrical energy, and

a conduit for removing the pieces of nucleus,

means for connecting said conduit to a source of vacuum,

said electrodes and said conduit being disposed within said annular wall, and

rigid means at the end of said housing adjacent the distal ends of said electrodes, said rigid means cooperating with said stiff, flexible annular wall to cause the distal ends of said electrodes to move away from each other to split the nucleus.

2. An instrument for surgical removal of the lens from the eye comprising

first and second coaxial, hollow, elongated, stiff, flexible members made of electrically non-conductive material,

said first hollow member being disposed within said second hollow member,

means for cutting a groove in the nucleus of the lens with bipolar energy and splitting the nucleus into pieces at the groove, said last named means comprising first and second electrodes, said electrodes including distal ends,

said electrodes being disposed in circumferentially spaced relation to each other and being disposed between said first and second hollow members to electrically isolate them, and

said first hollow member comprises means for removing the pieces of the lens.

3. An instrument as defined in claim 2 including

a third hollow, elongated, stiff, flexible member,

said first and second hollow, elongated members being received within said third hollow member and being spaced therefrom,

the space between said second hollow member and said third hollow member defining a conduit for the delivery of an irrigating fluid to area where the groove is being cut, and

means disposed in the space between said second and third hollow members to transfer a squeezing of said third hollow member to said electrodes to cause the distal ends of said electrodes to swing outwardly away from each other to split the nucleus.

4. An instrument as defined in claim 3 wherein

said means disposed in the space between said second and third hollow members comprises a plurality of rigid members that define a plurality of circumferentially spaced passages.

5. An instrument for surgical removal of the lens from the eye comprising

means for cutting a groove in the nucleus of the lens with bipolar electrical energy and splitting the nucleus at the groove into pieces, and

means for removing the pieces of nucleus,

means for cutting a groove in the nucleus of the lens with bipolar electrical energy and splitting the nucleus at the groove comprising first and second electrodes, said electrodes including distal ends,

said electrodes being in mutually-facing relation,

an elongated diametrically extending, non-conductive member disposed between said electrodes to electrically separate them from each other, and

each of said electrodes cooperates with said non-conductive member to define a first conduit for applying an irrigating fluid to the area where cutting is taking place and a second conduit for removing material from said area.

6. An instrument as defined in claim 5 including

first and second coaxial layers of concentric electrically non-conductive, stiff, flexible material disposed on each side of said diametrically extending, elongated non-conductive member, and

each of said electrodes is disposed between said coaxial layers on each side of said diametrically extending, elongated non-conductive member.

7. An instrument as defined in claim 6 including

a rigid annular member supported by said third member at its end adjacent the distal ends of said electrodes.

8. The method of surgically removing the lens from the eye comprising the steps of

cutting a groove in the nucleus of the lens with bipolar electrical energy,

splitting said nucleus, and

removing the pieces of nucleus.

9. The method as defined in claim 8 wherein

said steps of cutting, splitting and removing are accomplished by using an instrument that remains in the eye during and between said steps.

10. The method as defined in claim 9 including the step of

applying an irrigating fluid to the nucleus during cutting.

Apparatus and method of determining fertility status

2007-12-31T17:25:00.000-08:00

Abstract

A fertility computer is disclosed having the ability to store information about a users past menstrual cycle history, basal body temperature, gynecological disorders, which along with certain prediction indicators is used to statistically predict when ovulation will occur. The prediction indicators are based on information concerning the current status of certain body indicators such as mucus change, spotting in the middle of a cycle or a sore throat. This information is processed in accordance with a predetermined program which ascribes certain values to the above parameters to predict the present fertility status of the user.

Patent number: 4465077
Filing date: Nov 12, 1981
Issue date: Aug 14, 1984
Inventor: Howard Schneider
Primary Examiner: Francis J. Jaworski

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What is claimed is:

1. A fertility computer comprising:

(a) storage means for storing data indicating:

(i) the day of the week, DW;

(ii) the day of a menstrual cycle, DC;

(iii) a user's average cycle length, CL;

(iv) the day of a menstrual cycle in which mucus change occurred, DM;

(v) the relative value of the change in (iv);

(vi) a plurality of the most recent Basal Body Temperature (BBT) readings of the user T(1)-T(N);

(vii) the number of menstrual cycles in which the computer has been used by the user, CN; and

(viii) a plurality of discrepancy indicators F1-F(n);

(b) data processing means for utilizing the above data to provide an indication to the user of current fertility status;

(c) switch means operable by a user for inputting data with respect to a user's menstrual cycle parameters, basal body temperature, and physical disturbances into said data processing means;

(d) a temperature sensor for producing an analog temperature signal indicative of the user's basal body temperature;

(e) converter means for converting said analog signal to a digital signal; and

(f) display means for displaying to the user whether of not the temperature sensor is in a functional position and when it is permissible to remove the sensor from the functional position.

2. The apparatus of claim 1 wherein the fertility status is computed by ascribing different values to such data depending upon:

(a) the liklihood of a discrepancy, or

(b) the user's average cycle length, or

3. The apparatus of claim 2 wherein the discrepancy indicators are one or more of the following:

(a) a cycle of more than 40 days or less than 20 days;

(b) spotting within a cycle.

4. The apparatus of claim 3 wherein a factor in the computation is whether or not a BBT rise or drop has been completed.

5. A self-contained system for measuring and analyzing data which is indicative of a user's fertility and pregnancy status, comprising:

(a) a housing;

(b) an electrical power source inside said housing;

(c) switches mounted on said housing including a first switch to be pressed when the user senses blood per vagina indicative of a new period, a second switch to be pressed when a dry to wet change in the cervical mucus is sensed by the user, a third switch to be pressed when a disturbance in physical condition such as feeling ill is sensed by the user, and a fourth switch to be pressed when the user makes a mistake pressing one of the above switches and wishes to correct this mistake;

(d) a temperature sensor coupled to the housing comprising a thermistor which need not measure temperature accurately but only in a repeatable fashion;

(e) display means indicating

(i) correct operation of the system and

(ii) suitable power or

(iii) problems with either,

(iv) that the temperature sensor is still to be kept in a functional position within the mouth,

(v) the probability that the user is in the fertile phase of her menstrual cycle, and

(vi) the probability that the user is pregnant;

(f) a permanent memory consisting of a low power random-access-memory (RAM) device to which electric power is constantly applied and which is used to store among other data the current day of the menstrual cycle, lengths of a certain number of previous menstrual cycles if they exist, and values related in a predictable fashion to a number of previous or current temperature readings;

(g) a microprocessor coupled to an oscillator circuit, a read-only-memory (ROM), and said random-access-menmory (RAM) and input-output signal conditioners where said microprocessor interacts with the various elements it is attached to in accordance with a controlling algorithm preprogrammed in the ROM;

(h) self-test circuitry and logic means to determine whether circuit elements, including the electric power source and random-access-memory, are functional and convey this information to the user via said display means; and,

(i) temperature measurement and logic means to convert measured temperature of the temperature sensor to a digital signal related to the observed temperature and indicate to the user to keep the temperature probe in a functional position and to provide a signal to said display means until a certain period of time and/or certain thermal equilibrium is achieved.

6. The system of claim 5 including logic means for giving lesser or zero value to the digital signal representative of observed temperature if said third switch is pressed.

7. The system of claim 5 including logic means to disregard input from the first switch at the initial portion of the menstrual cycle.

8. The system of claim 5 including logic means to indicate that a new period is starting if the first switch has been pressed on at least two consecutive days.

9. The system of claim 5 including logic means to avoid obtaining and/or storing temperature measurements during the initial part of the menstrual cycle.

10. The system of claim 5 including:

logic means to allow computation from the stored cyclic information of a differential value which indicates the beginning of the fertile phase of the menstrual cycle and where said differential value is made smaller by previous menstrual cycles of short duration and by determination that the stored information is indicative of a relatively new unit and where said differential value is not used to determine the start of the fertile phase if the second switch is pressed during an appropriate time of the menstrual cycle but at a day of the current cycle smaller than the said differential value.

11. The system of claim 5 including logic means to disregard input from the second switch at the initial portion of the menstrual cycle.

12. The system of claim 5 including logic means to interpret stored temperature measurements to determine fertility status and ovulation wherein a user's temperature measurements taken on days of cycle smaller than the differential value are used to construct a representative baseline temperature and at days of a cycle equal to or greater than the differential value, a day's temperature measurement is interpreted as elevated if it exceeds the representative baseline temperature by a preset threshold value which value is in turn determined by a sensitivity value, and wherein a certain number of days after ovulation determination has been completed the day's temperature measurement is interpreted as depressed if the temperature measurement is exceeded by a representative baseline temperature value constructed from temperature measurements immediately following ovulation by a preset threshold value which is in turn determined by said sensitivity value, and wherein ovulation is determined to have occurred if three recent temperature measurements are interpreted to have been elevated where said elevated temperature measurements occur consecutively or within a duration of four or five days and wherein a certain number of measurements are associated with no disturbances and a certain number are associated with disturbances and a minority are not interpreted as elevated, and wherein the indication of no fertility or infertility is given to the user after ovulation determination is complete, where an indication of pregnancy is given to the user if the day of cycle is greater than the expected menstrual cycle length and several recent temperature values are not interpreted as depressed in a consecutive fashion.

13. An electronic apparatus for measuring and analyzing data which is indicative of a user's fertility and pregnancy status according to claim 5 further comprising means for determining and indicating the start of the next menstrual cycle.

14. An electronic apparatus for measuring and analyzing data which is indicative of a user's fertility and pregnancy status according to claim 5 further comprising logic means to indicate low and maximum probability of fertility and/or pregnancy.

Dental Drill

2007-12-28T04:26:00.000-08:00

Patent number: 423344
Filing date: Jul 10, 1889
Issue date: Mar 11, 1890
Inventor: ARWED BETTER

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Method of assisting weight loss

2007-11-30T08:38:00.000-08:00

Abstract

A method of assisting weight loss involving the combined administration of a rauwolfia alkaloid and at least one antidepressant, selected from the groups consisting of aminoazoles, phenoxyphenylpropylamines, and aminopropiophenones, in a daily regimen with the optional co-administration of one or more sympathomimetic anorexic agents. In a typical embodiment of this method, reserpine and trazodone are administered in a daily regimen with diethylpropion, fenfluramine or both diethylpropion and fenfluramine.

Patent number: 4895845
Filing date: Sep 15, 1986
Issue date: Jan 23, 1990
Inventor: John C. Seed
Primary Examiner: Raymond J. Henley, III

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What is claimed is:

1. A method of assisting weight loss in a human in need thereof which comprises administering to said human, over a sustained period of time, both a rauwolfia alkaloid in the form of reserpine, and at least one antidepressant selected from the group consisting of trazodone, bupropion and fluoxetine in an administration regimen sufficient to supply effective daily dosages thereof for assisting weight loss.

2. The method of claim 1 wherein said antidepressant is trazodone and both reserpine and trazodone are administered concomitantly.

3. The method of claim 1 wherein the daily dosage of reserpine is between about 0.001 and about 0.01 milligram per kilogram of human body weight.

4. The method of claim 1 wherein said antidepressant is trazodone and the daily dosage of trazodone is between about 0.1 and about 6.0 milligram per kilogram of human body weight.

5. The method of claim 1 wherein said antidepressant is fluoxetine and both reserpine and fluoxetine are administered concomitantly.

6. The method of claim 1 wherein the daily dosage of reserpine is between about 0.001 and about 0.01 milligram per kilogram of human body weight.

7. The method of claim 1 wherein said antidepressant is fluoxetine and the daily dosage of fluoxetine is between about 0.1 and about 1.5 milligram per kilogram of human body weight.

8. The method of claim 1 wherein the rauwolfia alkaloid is reserpine, and both trazodone and fluoxetine are administered, said reserpine, trazodone, and fluoxetine being administered in a regimen sufficient to supply effective daily dosages thereof for assisting weight loss.

9. The method of claim 1 wherein the rauwolfia alkaloid is reserpine, and trazodone, bupropion, and fluoxetine are administered, said reserpine, trazodone, bupropion and fluoxetine being administered in a regimen sufficient to supply effective daily dosages thereof for assisting weight loss.

10. The method of claim 1 wherein the rauwolfia alkaloid is reserpine, and both trazodone and bupropion are administered, said reserpine, trazodone, and bupropion being administered in a regimen sufficient to supply effective daily dosages thereof for assisting weight loss.

Weight loss device and method

2007-11-30T08:34:00.000-08:00

Abstract

Patent number: 4485805
Filing date: Aug 24, 1982
Issue date: Dec 4, 1984
Inventor: Lawrence H. Foster, Jr.
Assignee: Gunther Pacific Limited of Hong Kong

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What is claimed is:

1. Apparatus for use in achieving a loss of weight in an overweight person comprising:

an inflatable device;

means for placing said device within the stomach of the person without surgery;

additional means for inflating said device with liquid after it has been placed in the person's stomach;

a pull string having a rollable finger cot attached at one end, and a releasable, self-closing fill valve as part of the inflatable device.

3. The method of placing a gastric cavity filling device within an obese person's gastric cavity without any surgery, comprising the steps of:

providing an inflatable device in deflated form;

attaching a fill tube to the inflatable device;

inserting a hollow tube containing a string therethrough into the person's mouth, esophagus and gastric cavity;

releasably attaching the deflated device with fill tube attached to one end of the string;

pulling the other end of the string to pull the deflated device into the person's gastric cavity;

inflating the deflated device through the fill tube and after suitable inflation of the device;

removing all the placing apparatus so that the inflated device remains free-floating in the person's gastric cavity without any attachments thereto.

4. The method of claim 3, with the further steps of:

inserting a stiffener member into the hollow tube containing the string therethrough prior to the step of pulling the string.

5. The method of claim 4, with the additional step of using liquid containing an X-ray opaque substance therein for inflating the device.

Ultrasonic imaging system, a non-interlaced scanning method

2007-11-27T07:19:00.000-08:00

Abstract

An ultrasonic imaging system for an ultrasonic imaging unit generating ultrasonic image data of an interlaced scanning mode, includes a display of a non-interlaced scanning mode and a scanning mode converter for converting ultrasonic image data of the interlaced scanning mode received from the ultrasonic imaging unit into data of a non-interlaced scanning mode and supplying the ultrasonic image data of the non-interlaced scanning mode to the non-interlaced scanning mode display, to thereby provide an ultrasonic image having a better quality of picture in comparison with the interlaced scanning mode. The only ultrasonic image data in which the ultrasonic image data is displayed together with additional data on a screen by the image display of the non-interlaced scanning mode, is converted in the interlaced mode, thereby recording the ultrasonic image data via the conventional VCR.

Patent number: 5777683
Filing date: May 8, 1996
Issue date: Jul 7, 1998
Inventors: Yong-heon Park, Byung-sun Yoo, Seok-bin Ko
Assignee: Medison Co., Ltd.

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What is claimed is:

1. An ultrasonic imaging system for an ultrasonic imaging unit generating ultrasonic image data of an interlaced scanning mode, said ultrasonic imaging system comprising:

a display of a non-interlaced scanning mode;

a first scanning mode converter for converting ultrasonic image data of the interlaced scanning mode received from said ultrasonic imaging unit into data of a non-interlaced scanning mode and supplying the ultrasonic image data of the non-interlaced scanning mode to said non-interlaced scanning mode display;

an interlaced scanning mode monitor; and

a second scanning mode converter for converting non-interlaced scanning mode data from said first scanning mode converter to interlaced data for display on said monitor.

2. The ultrasonic imaging system according to claim 1, wherein said scanning mode converter processes the ultrasonic image data obtained by the scanning mode conversion to be displayed on the whole screen of said display.

3. An ultrasonic imaging system for an ultrasonic imaging unit generating ultrasonic image data of an interlaced scanning mode, said ultrasonic imaging system comprising:

a display of a non-interlaced scanning mode;

a scanning mode converter for converting ultrasonic image data of the interlaced scanning mode received from said ultrasonic imaging unit into data of a non-interlaced scanning mode and supplying the ultrasonic image data of the non-interlaced scanning mode to said non-interlaced scanning mode display;

a graphic adapter; and

a window setter for processing the ultrasonic image data from said scanning mode converter to be displayed in a window of a first size smaller than that of the whole screen, processing additional information data applied via said graphic adapter to be displayed on the other areas excluding the window of the first size, and supplying the resulting data to said display.

4. The ultrasonic imaging system according to claim 3, further comprising means for detecting the ultrasonic image data from the data output from said window setter and converting the detected ultrasonic image data into data of an interlaced scanning mode.

Device to permit offpump beating heart coronary bypass surgery

2007-11-21T23:39:00.000-08:00

Abstract

A heart retractor links lifting of the heart and regional immobilization which stops one part of the heart from moving to allow expeditious suturing while permitting other parts of the heart to continue to function whereby coronary surgery can be performed on a beating heart while maintaining cardiac output unabated and uninterrupted. Circumflex coronary artery surgery can be performed using the heart retractor of the present invention. The retractor includes a plurality of flexible arms and a plurality of rigid arms as well as a surgery target immobilizing element. One form of the retractor can be used in minimally invasive surgery, while other forms of the retractor can accommodate variations in heart size and paracardial spacing.

Patent number: 6019722
Filing date: Sep 17, 1997
Issue date: Feb 1, 2000
Inventors: Paul A. Spence, Warren Williamson, IV
Assignee: Guidant Corporation

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What is claimed is:

1. A retractor for use in heart surgery comprising:

a rigid gross support means for engaging a heart to support the heart when the heart is oriented for surgery and including a multipositional support element fixed to a stationary support;

means for immobilizing selected portions of the heart while permitting non-immobilized portions to move in a manner that continues heart operation; and

a surgery target immobilizing means connected to said support element and engaging the heart adjacent to a surgery target for immobilizing the heart at and immediately adjacent to the surgery target

whereby the heart is supported and free to operate during surgery while being locally immobilized at the surgery target.

2. The heart retractor defined in claim 1 wherein said gross support means includes a cup-shaped element for engaging and supporting the heart adjacent to the apex section of the heart.

3. The heart retractor defined in claim 2 wherein said support means further includes a plurality of rigid support arms each connected at one end thereof to said stationary support element and having a heart-attaching element thereon.

4. The heart retractor defined in claim 3 wherein said each heart-attaching element includes a suction attachment point.

5. The heart retractor defined in claim 3 wherein said support means further includes a vacuum source and means fluidically connecting said vacuum source to said cup-shaped element and further including means fluidically connecting said vacuum source to each heart-attaching element.

6. The heart retractor defined in claim 2 wherein said support means further includes a vacuum source and means fluidically connecting said vacuum source to said cup-shaped element.

7. The heart retractor defined in claim 1 wherein said target-immobilizing element includes a U-shaped target-defining element having two legs and means thereon for engaging the heart to position one leg on each side of the surgery target.

8. The heart retractor defined in claim 7 wherein said target-immobilizing element further includes a rigid arm attached to said U-shaped element and to said stationary support element.

9. The heart retractor defined in claim 1 wherein said means for immobilizing selected portions of the heart includes attachment means thereon for attaching to the surface of the heart.

10. A heart retractor for use in heart surgery comprising:

support means for supporting the gross weight of a heart to support the heart when the heart is oriented for surgery and including a main support arm having means at one end thereof for mounting the support arm on a stationary support; and

means for immobilizing selected portions of the heart and permitting other sections to move as required to continue heart operation during surgery, said immobilizing means including at least one rigid support arm connected at one end thereof to said support means and having means thereon for releasably attaching said rigid support arm to the heart, and at least one flexible support arm connected at one end thereof to said support means and having means on another end thereof for releasably attaching said flexible support arm to the heart.

11. The heart retractor defined in claim 10 wherein said means for immobilizing selected portions of the heart includes a plurality of flexible arms each connected at one end thereof to said support means and each having a heart-engaging member thereon.

12. The heart retractor defined in claim 11 wherein each heart-engaging member is a suction attachment point.

13. The heart retractor defined in claim 2 further including a surgery target immobilizing element having one end thereof connected to said support means and heart-engaging elements on another end thereof.

14. A retractor for use in minimally invasive heart surgery comprising:

support means for engaging a heart to support the heart when the heart is oriented for surgery and including a handle having a distal end and a proximal end, said proximal end being located outside of a patient during surgery, a support element fixed to said distal end, and rigid elements fixed to said distal end and engaging and supporting chosen sections of the heart; and

means for immobilizing selected portions of the heart while permitting non-immobilized portions to move in a manner that continues heart operation

whereby the heart is supported and free to operate during minimally invasive surgery while being immobilized at selected locations.

15. The retractor defined in claim 14 wherein said means for immobilizing selected portions of the heart includes a plurality of flexible arms each connected to said handle.

16. The retractor defined in claim 15 wherein each rigid element includes a heart-engaging element and further includes a vacuum source fluidically connected to each heart-engaging element.

17. The retractor defined in claim 14 wherein said support means includes a cup-shaped element fixed to the distal end of said handle.

18. The retractor defined in claim 17 further including a vacuum source fluidically connected to said cup-shaped element.

19. A retractor for use in heart surgery comprising:

support means for engaging a heart to support the heart when the heart is oriented for surgery and including a support element fixed to a stationary support and rigid elements engaging and supporting chosen sections of the heart;

means for immobilizing selected portions of the heart while permitting non-immobilized portions to move in a manner that continues heart operation

whereby the heart is supported and free to operate during surgery while being locally immobilized at the surgery target.

20. A heart positioning device for use in cardiac surgery comprising:

support means for engaging a heart to support the heart when the heart has been oriented into an unnatural position or orientation for coronary surgery;

means for attaching said support means to the heart so the heart operates with uncompromised ventricular function when the heart is oriented into an unnatural position or orientation for coronary surgery:

means engaging sections of the heart to immobilize the sections engaged while permitting non-engaged sections of the heart to move in a manner whereby essentially unabated cardiac output is maintained during surgery while the heart is regionally immobilized.

21. The heart retractor defined in claim 20 wherein said support means includes a means for engaging the heart sufficiently to support the heart during coronary surgery.

22. The heart retractor defined in claim 20 wherein said support means includes arms which have locking elements for permitting the arms to be moved into position and then locked in position.

23. The heart retractor defined in claim 20 further including a surgery target immobilizing element connected to said support means and engaging the heart adjacent to a surgery target for immobilizing the heart at and immediately adjacent to the surgery target.

24. A heart retractor for use in heart surgery comprising:

support means for engaging an apex portion of a heart to support the heart when the heart is lifted for surgery and including a main support arm having means at one end thereof for mounting the support arm on a stationary support; and

means for immobilizing selected portions of the heart and permitting other sections to move as required to continue heart operation during surgery, said immobilizing means including at least one rigid support arm connected at one end thereof to said support means and having means on another end thereof for releasably attaching said rigid support arm to the heart, at least one flexible support arm connected at one end thereof to said support means and having means thereon for releasably attaching said flexible support art to the heart.

25. The heart retractor defined in claim 24 further including a surgery target immobilizing element having one end thereof connected to said support means and heart-engaging elements thereon.

26. A retractor for use in heart surgery comprising:

a main support;

a gross support means for engaging a heart and supporting the heart when the heart is oriented for surgery, said gross support means being attached to said main support;

a fine support means for supporting portions of the heart during surgery, said fine support means being attached to said gross support means with non-supported portions of the heart moving in a manner whereby essentially unabated cardiac output is maintained during surgery while the heart is regionally immobilized at supported portions and including rigid elements engaging and supporting chosen sections of the heart.

27. A retractor for use in heart surgery comprising:

a main support;

a gross support means for engaging a heart and supporting the heart when the heart is oriented for surgery, said gross support means being attached to said main support and including means for adjusting the shape of said gross support means;

28. The retractor defined in claim 27 wherein said means for adjusting the shape of said gross support means includes a fastener attaching two arms together, with said two arms engaging the heart to support the gross weight of the heart.

29. The retractor defined in claim 27 further including attachment means on said fine support means for contacting the heart.

30. The retractor defined in claim 29 wherein said attachment means include suction points.

31. The retractor defined in claim 27 further including a support arm and a surgery target immobilizing element attached to said support arm.

32. A heart positioning device for use in cardiac surgery comprising:

a stationary support;

a rigid arm connected to said stationary support;

a flexible element connected to said rigid arm;

means on said flexible element for releasably attaching said flexible element to a heart to orient the heart into an unnatural position or orientation for coronary surgery and so the heart operates with uncompromised ventricular function when oriented into the unnatural position or orientation during coronary surgery.

33. The heart positioning device defined in claim 32 further including a second flexible element connected to said rigid arm.

34. The heart positioning device defined in claim 32 wherein said rigid arm is multipositional.

35. A heart positioning device for use in cardiac surgery comprising:

a stationary support for orienting the heart into an unnatural position or orientation for coronary surgery;

a flexible element connected to said stationary support for supporting the heart in a manner so the heart operates with uncompromised ventricular function when the heart is oriented into the unnatural position during coronary surgery; and

means on said flexible element for releasably attaching said flexible element to the heart.

36. A heart positioning device for use in cardiac surgery comprising:

a stationary support for orienting the heart into an unnatural position or orientation for coronary surgery;

a rigid arm connected to said stationary support;

a flexible element connected to said stationary support;

means on said flexible element for releasably attaching said flexible element to a heart in a manner so the heart operates with uncompromised ventricular function when the heart is oriented into the unnatural position during coronary surgery.

37. The heart positioning device defined in claim 36 further including a second flexible element connected to said rigid arm.

38. The heart positioning device defined in claim 36 wherein said stationary support is multipositional.

39. A heart positioning device for use in cardiac surgery comprising:

a frame;

a stationary support attached to said frame for orienting the heart into an unnatural position or orientation for coronary surgery;

means on said flexible element for releasably attaching said flexible element to the heart.

40. The heart positioning device defined in claim 39 further including a second flexible element connected to said stationary support.

41. A heart positioning device for use in cardiac surgery comprising:

a stationary support;

a flexible element connected to said stationary support for supporting a heart in a manner so the heart operates with uncompromised ventricular function when the heart is oriented into an unnatural position or orientation during coronary surgery; and

means on said flexible element for releasably attaching said flexible element to the heart.

42. The device defined in claim 41 wherein said stationary support is multipositional for allowing the stationary support to move in a plurality of orientations and positions.

Method for coronary artery bypass

2007-11-21T23:37:00.000-08:00

Abstract

The invention comprises a method for performing a coronary artery bypass graft on a beating heart under thoracoscopic visualization without opening the chest wall. At least one small opening is formed in the patient's chest, a target artery for an arterial blood supply is located, instruments are introduced through one or more small openings formed in the patient's chest to prepare the target artery for fluid connection to the coronary artery, and instruments are introduced through one or more small openings formed in the patient's chest to connect the target artery to the coronary artery distal from a stenosis. In a preferred embodiment, a minimal left anterior intercostal thoracotomy provides access to form an anastomosis between the left internal mammary artery (LIMA) and the left anterior descending artery (LAD) while thoracoscopic viewing facilitates harvesting the LIMA. In other embodiments, access to the patient's heart may be obtained through a trocar sheath or other...

Patent number: 5888247
Filing date: Apr 10, 1995
Issue date: Mar 30, 1999
Inventor: Frederico J. Benetti
Assignee: Cardiothoracic Systems, Inc

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What is claimed is:

1. A method for performing a coronary artery bypass graft procedure on the beating heart of a human patient comprising:

forming a thoracotomy in the chest of the human patient to provide access to the beating heart,

locating a target artery having an arterial blood supply,

introducing a retractor into said thoracotomy, followed by manipulating said retractor to spread the chest both horizontally and vertically,

forming an arteriotomy distal to a stenosis in a coronary artery of said beating heart, and

bypassing said stenosis in said coronary artery using said arterial blood supply of said target artery to establish arterial blood flow distal to said stenosis.

2. The method of claim 1 wherein the thoracotomy is a minimal thoracotomy having a size of incision which is not substantially greater than 12 cm.

3. The method of claim 1 or 2 further comprising the step of stabilizing said beating heart.

4. The method of claim 3 wherein said coronary artery of said beating heart is stabilized by a method selected from the group consisting of contacting tissue proximate to said artery with forcep means, and tensioning ligatures about said coronary artery.

5. The method of claim 3 wherein said beating heart is stabilized by forcep means engaging tissue proximate to said coronary artery on either side of said arteriotomy.

6. The method of claim 1 wherein said coronary artery is selected from the group consisting of the left anterior descending, diagonal, circumflex, obtuse marginal, ramus intermedius, right coronary and posterior descending artery.

7. The method of claim 1 wherein said target artery is selected from the group consisting of the gastroepiploic artery, the right internal mammary artery, and the left internal mammary artery.

8. The method of claim 7 further comprising the step of separating said target artery from its support using instruments introduced through said thoracotomy.

9. The method of claim 7 further comprising the step of separating said target artery from its support, wherein said separation is visualized by a thoracoscope.

10. The method of claim 2 wherein said minimal thoracotomy is intercostal and in the left anterior chest, and wherein said target artery is the left internal mammary artery and said coronary artery is selected from the group consisting of the left anterior descending artery, a diagonal artery, and the circumflex artery.

11. The method of claim 1 wherein the formation of said arteriotomy is visualized by a thoracoscope.

12. The method of claim 1 wherein completion of said anastomosis is visualized by a thoracoscope.

13. The method of claim 1 wherein said anastomosis is completed using a graft selected from the group consisting of a harvested artery, a harvested vein, and a synthetic graft.

14. The method of claim 1 wherein said anastomosis is between the aorta and said coronary artery and is completed using a graft selected from the group consisting of a harvested artery, a harvested vein, and a synthetic graft.

15. A method for performing a coronary artery bypass graft procedure on the beating heart of a human patient comprising:

forming an intercostal minimal thoracotomy in the left anterior chest of the human patient to provide access to the left internal mammary artery and a coronary artery selected from the group consisting of the left anterior descending artery, a diagonal artery, and the circumflex artery of the beating heart,

introducing a retractor into said intercostal minimal thoracotomy, followed by providing access to said left internal mammary artery by manipulating said retractor to spread the chest both horizontally and vertically,

locating the left internal mammary artery to provide an arterial blood supply by a method selected from the group consisting of direct vision of said left internal mammary artery and insertion of a thoracoscope into the left anterior chest,

separating said left internal mammary artery from its support using instruments introduced through said intercostal minimal thoracotomy,

stabilizing said coronary artery of said beating heart,

forming an arteriotomy in said coronary artery of said beating heart wherein said arteriotomy is distal to a stenosis in said coronary artery, and

completing an anastomosis of said left internal mammary artery to said coronary artery to establish arterial blood flow distal to said stenosis.

16. The method of claim 15 wherein said intercostal minimal thoracotomy has a size of incision which is not substantially greater than 12 cm.

17. The method of claim 15 wherein said coronary artery of said beating heart is stabilized by a method selected from the group consisting of contacting tissue proximate to said coronary artery with forcep means, and tensioning ligatures about said coronary artery.

18. The method of claim 15 wherein said beating heart is stabilized by forcep means engaging tissue proximate to said coronary artery on either side of said arteriotomy.

19. The method of claim 15 wherein said separation of said left internal mammary artery from its support base is visualized by a thoracoscope.

20. The method of claim 15 wherein the formation of said arteriotomy in said coronary artery is visualized by a thoracoscope.

21. The method of claim 15 wherein the completion of said anastomosis is visualized by a thoracoscope.

22. The method of claim 15 wherein said anastomosis is completed using a graft selected from the group consisting of a harvested artery, a harvested vein, and a synthetic graft.

Cardiac sling for circumflex coronary artery surgery

2007-11-21T21:00:00.000-08:00

Abstract
A cardiac sling for supporting the heart during surgery a support a polymeric film net of interconnecting ribs of polymeric material for applying, in use, sufficient pressure to the portions of the surface of the heart adjacent the ribs to prevent hemorrhage from the anastomotic site of bypass grafting is disclosed.

Patent number: 4973300
Filing date: Sep 22, 1989
Issue date: Nov 27, 1990
Inventor: John T. M. Wright
Assignee: Pioneering Technologies, Inc.
Primary Examiner: Kerry Owens

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What is claimed is:

1. A cardiac sling for supporting the heart during surgery comprising:

a support portion comprising a latticework of ribs surrounding a multiplicity of holes formed in an elastomeric film sheet, the lattice work being so constructed an configured such that the holes have a minimum diameter of from about 0.25 to about 0.75 inch and the ribs are from about 0.062 to about 0.312 inches wide as to apply, sufficient pressure to the portions of the surface of the heart adjacent there is to prevent hemorrhage from the anastomotic site by bypass grafting;

and means for securing the support portion under the heart.

2. The cardiac sling of claim 1 wherein the elastomeric film sheet is formed of transparent polymer lightly colored a color which contrasts with blood and tissue.

3. The cardiac sling of claim 1 wherein the elastomeric film sheet is formed of polymeric material between about 0.005 and about 0.030 inches in thickness.

4. The cardiac sling of claim 1 wherein the elastomeric film sheet is formed of soft, smooth, matt finish, tear resistant, blood impervious polyurethane.

5. The cardiac sling of claim 1 wherein the means for securing the support portion under the heart comprises at least a pair of tapes extending from the support portion, at the support portion and tapes being formed of one unitary sheet of said polymeric film.

6. A cardiac sling for supporting the heart during surgery comprising:

a support portion formed of soft, smooth, tear resistant, blood impervious transparent polyurethane colored with a color which contrasts with the color of tissue and blood having a matt finish between about 0.005 and about 0.030 inches in thickness, having a multiplicity of hexagonal holes having a diameter of from about 0.25 to about 0.75 inch as measured between opposed flat sides thereof separated by interconnecting ribs from about 0.062 to about 0.312 inches wide defining six sides thereof forming a net of said interconnecting ribs for applying, in use, sufficient pressure to the portions of the surface of the heart adjacent the ribs to prevent hemorrhage from the anastomotic site of bypass grafting;

and means for securing the support portion under the heart.

7. A cardiac sling for supporting the heart during surgery comprising:

a support portion formed of soft, smooth, tear resistant, blood impervious transparent polyurethane film colored with a color which contrasts with the color of tissue and blood and having a matt finish, thefilm being between about 0.005 and about 0.030 inches in thickness, having a multiplicity of hexagonal holes having a diameter of from about 0.25 to about 0.75 inch as measured between opposed flat sides thereof separated by interconnecting ribs from about 0.062 to about 0.312 inches wide defining six sides thereof forming a net of said interconnecting ribs for applying, in use, sufficient pressure to the portions of the surface of the heart adjacent the ribs to prevent hemorrhage from the anastomotic site of bypass grafting;

and at least a pair of tapes extending from the support portion for securing the support portion under the heart;

the support portion and tapes being formed of one unitary sheet of said polyurethane film.

Monoclonal antibody specific for DNA.RNA hybrids

2007-11-21T20:58:00.000-08:00

Abstract

A monoclonal antibody specific for DNA.multidot.RNA duplexes, particularly DNA.multidot.RNA heteropolymer duplexes, characterized by having cross-reactivity for binding to single- or double-stranded DNA or RNA as measured by competitive immunoassay of less than about 1:1000, and preferably less than 1:10,000, and an affinity for DNA.multidot.RNA heteropolymer duplexes greater than 10.sup.9 L/mole. The monoclonal antibody is prepared by conventional somatic cell hybridization techniques wherein the host animal is preferably immunized with an immunogen comprising a random DNA.multidot.RNA heteropolymer. The antibody, particularly in a labeled form, is useful in the specific detection of DNA.multidot.RNA duplexes in a test medium such as a nucleic acid hybridization assay mixture.

Patent number: 4833084
Filing date: Aug 26, 1985
Issue date: May 23, 1989
Inventor: Robert J. Carrico
Assignee: Miles Inc.
Primary Examiner: Jeremy M. Jay

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What is claimed is:

1. The monoclonal antibody secreted by hybridoma cell line ATCC HB 8730.

2. Hybridoma cell line ATCC HB 8730.

Arabinonucleic acid probes for DNA/RNA assays

2007-11-21T20:57:00.000-08:00

Abstract

A novel nucleic acid, arabinonucleic acid, is provided as a probe in nucleic acid assays. The arabinose moiety of the probe can be detected with anti-arabinose antibody-label conjugates.

Patent number: 4760017
Filing date: Dec 23, 1985
Issue date: Jul 26, 1988
Inventor: Randy M. McCormick
Assignee: E. I. Du Pont de Nemours and Company
Primary Examiner: Robert Benson

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What is claimed is:

1. A probe for the detection of a preselected nucleic acid sequence comprising single stranded arabinonucleic acid consisting essentially of arabinonucleotides having 3' and 5' internucleotide linkages with a base linked at the 1' position, said base being selected from the group consisting essentially of adenine, guanine, cytosine, thymine and uracil, said bases having a sequence complementary to said preselected nucleic acid sequence.

2. A method for identifying a preselected nucleic acid sequence in a sample comprising the steps of:

(a) rendering the nucleic acid in said sample single-stranded;

(b) immobilizing the single-stranded nucleic acids onto a support;

(c) contacting said immobilized single-stranded nucleic acids with a single-stranded arabinonucleic acid consisting essentially of arabinonucleotides having 3' and 5' internucleotide linkages with a base linked at the 1' position, said base being selected from the group consisting essentially of adenine, guanine, cytosine, thymine and uracil, said bases having a sequence complementary to said preselected nucleic acid sequence, under conditions that allow a hybridization reaction to occur;

(d) washing said support to remove arabinonucleic acid not incorporated into the hybrid formed on the support; and

(e) determining the presence of arabinonucleic acid in the hybrid formed on the support by contacting it with an anti-arabinose antibody-label conjugate and detecting said label.

3. The method of claim 2 wherein the label is an enzyme.

Product and process for isolating DNA, RNA and proteins

2007-11-21T20:53:00.000-08:00

Abstract

Solutions and methods are disclosed for the effective, simple isolation/extraction of DNA, RNA and proteins from a single biological material sample, such as cells, tissues and biological fluids. The preferred solutions include effective amounts of a chaotropic agent(s), buffer, reducing agent, and may or may not include an organic solvent. Genomic DNA and total RNA can be isolated utilizing the solutions and methods of the invention in as little as 20 minutes, and proteins in as little as 30 minutes.

Patent number: 5945515
Filing date: Jul 31, 1995
Issue date: Aug 31, 1999
Inventor: Piotr Chomczynski
Primary Examiner: David S. Romeo

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What is claimed is:

1. A solution for isolating substantially pure and undegraded RNA, DNA and proteins from biological material, said solution comprising:

at least one chaotropic agent,

a buffer present in an amount sufficient to maintain the pH of said solution in the range of about 6 to about 7.5.

an organic solvent present at a concentration in the range of about 13 to about 23% (v/v) of said solution, and

at least one chelating agent.

2. The solution of claim 1 wherein said chelating agent is selected from the group consisting of ethylenediamine tetraacetic acid and citric acid.

3. The solution of claim 1 further comprising a detergent.

4. The solution of claim 3 wherein said detergent is selected from the group consisting of sarcosine and polyoxyethylenesorbitan.

5. A method of isolating substantially pure and undegraded RNA, DNA and proteins from biological material, comprising the steps of:

a) homogenizing a biological material sample in the solution of claim 2 to form an homogenate;

b) recovering substantially pure, undegraded RNA from the homogenate by sedimentation;

c) thereafter precipitating DNA in the remaining homogenate by adding an additional amount of organic solvent thereto, and recovering the precipitated DNA by one of sedimentation or spooling; and

d) thereafter precipitating proteins from the remaining homogenate by adding an additional amount of organic solvent thereto, and recovering the precipitated proteins by sedimentation.

6. The method of claim 5 wherein said additional amount of organic solvent added to precipitate DNA is added to achieve a concentration in the range of about 28 to about 38% (v/v).

7. The method of claim 6 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

8. The method of claim 5 wherein said additional amount of organic solvent added to precipitate proteins is added to achieve a concentration in the range of about 78 to about 82% (v/v).

9. The method of claim 8 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

10. A method of isolating substantially pure and undegraded RNA from biological material, comprising the steps of:

a) homogenizing a biological material sample in a solution of claim 1 to form an homogenate; and

b) recovering substantially pure RNA from the homogenate by sedimentation.

11. A method of isolating substantially pure and undegraded DNA from biological material, comprising the steps of:

a) homogenizing a biological material sample in a solution of claim 1 to form an homogenate; and

b) precipitating DNA in the homogenate by adding an additional amount of an organic solvent thereto for a concentration of organic solvent in the range of about 28% to about 38% (v/v), and recovering the precipitated DNA by one of spooling and sedimentation.

12. The method of claim 11 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

13. A method of isolating substantially pure and undegraded RNA, DNA and proteins from biological material, comprising the steps of:

a) homogenizing a biological material sample in a solution comprising:

at least one chaotropic agent, and

a buffer present in an amount sufficient to maintain the pH of said solution in the range of about 6 to about 7.5, to form an homogenate;

b) removing unhomogenized material from the homogenate by sedimentation;

c) precipitating RNA in the remaining homogenate by adding thereto an organic solvent to achieve a concentration in the range of about 13 to about 23% (v/v), and recovering the precipitated RNA by sedimentation;

d) thereafter precipitating DNA in the remaining homogenate by adding an additional amount of organic solvent thereto, and recovering the precipitated DNA by one of spooling or sedimentation; and

e) thereafter precipitating proteins from the remaining homogenate by adding an additional amount of an organic solvent thereto, and recovering the precipitated proteins by sedimentation.

14. The method of claim 13 wherein said organic solvent used for precipitating RNA is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethysulfoxide.

15. The method of claim 13 wherein said additional amount of organic solvent added to precipitate DNA is added to achieve a concentration in the range of about 28 to about 38% (v/v).

16. The method of claim 15 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

17. The method of claim 13 wherein said additional amount of organic solvent added to precipitate proteins is added to achieve a concentration in the range of about 78 to about 82% (v/v).

18. The method of claim 17 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

19. A method of isolating substantially pure and undegraded RNA from biological material, consisting essentially of the following steps:

a) homogenizing a biological material sample in a solution consisting essentially of:

at least one chaotropic agent, and

a buffer present in an amount sufficient to maintain the pH of said solution in the range of about 6 to about 7.5, to form an homogenate;

b) removing unhomogenized material from the homogenate by sedimentation; and

c) precipitating RNA in the homogenate by adding thereto an organic solvent to achieve a concentration in the range of about 13 to about 23% (v/v), and recovering the precipitated RNA by sedimentation.

20. The method of claim 19 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

21. A method of isolating substantially pure and undegraded DNA from biological material, consisting essentially of the following steps:

a) homogenizing a biological material in a solution comprising:

at least one chaotropic agent, and

a buffer present in an amount sufficient to maintain the pH of said solution in the range of about 8 to about 12, to form an homogenate;

b) removing unhomogenized material from the homogenate by sedimentation, and

c) precipitating DNA in the homogenate by adding thereto an organic solvent to achieve a concentration in the range of about 28 to about 38% (v/v), and recovering the precipitated DNA by one of spooling or sedimentation.

22. The method of claim 21 wherein said organic solvent is selected from the group consisting of lower alcohols, acetone, polyethylene glycol and dimethylsulfoxide.

Shelf-stable product and process for isolating RNA, DNA and proteins

2007-11-21T20:50:00.000-08:00

Abstract

Shelf-stable solvent solutions and methods for simultaneously isolating RNA, DNA and proteins from biological samples are disclosed. The solvent solutions include phenol and a guanidinium compound, preferably at a concentration below about 2M, which is effective in isolating substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from the same biological sample.

Patent number: 5346994
Filing date: Jan 28, 1992
Issue date: Sep 13, 1994
Inventor: Piotr Chomczynski

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What is claimed is:

1. A solvent solution comprising: effective amounts of phenol, a guanidinium compound and a thiocyanate compound selected from the group consisting of ammonium thiocyanate and sodium thiocyanate for extracting substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from biological tissue.

2. The solvent solution of claim 1, said thiocyanate compound being present at a concentration in the range of about 0.1-0.6M, based on the total volume of said solvent solution.

3. A solvent solution comprising: effective amounts of phenol, a guanidinium compound and sodium acetate present at a concentration of about 0.1M, based on the total volume of said solvent solution, said solvent solution having a pH of about 5.0 for extracting substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from biological tissue.

4. A solvent solution comprising: effective amounts of phenol, a guanidium compound and a phenol solubilizer for extracting substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from biological tissue.

5. The solvent solution of claim 4, said phenol solubilizer being glycerol.

6. The solvent solution of claim 5, said glycerol being present in the range of about 3%-10% by volume of said solvent solution, based on the total volume of said solvent solution.

7. The solvent solution of claim 6, said phenol being present in the range of about 30%-50% by volume of said solvent solution, based on the total volume of said solvent solution.

8. A solvent solution for extracting substantially pure RNA, DNA and proteins from biological tissue, said solvent solution comprising:

(a) guanidinium thiocyanate at a concentration in the range of about 0.5-2M, based on the total volume of said solvent solution;

(b) a buffer in an amount sufficient to maintain the pH of said solvent solution in the range of about 4-6;

(d) a phenol solubilizer in the amount of about 3%-10% by volume based on the total volume of said solvent solution.

9. The solvent solution of claim 8 further comprising ammonium thiocyanate at a concentration in the range of about 0.1-0.6M, based on the total volume of said solvent solution.

10. The solvent solution of claim 8, said phenol solubilizer being glycerol.

11. The solvent solution of claim 8, said guanidinium thiocyanate concentration being about 0.8M.

12. The solvent solution of claim 9, said ammonium thiocyanate concentration being about 0.4M.

13. The solvent solution of claim 8, said buffer being sodium acetate.

14. The solvent solution of claim 13, said sodium acetate being present at a concentration of about 0.1M, based on the total volume of said solvent solution, said solvent solution having a pH of about 5.0.

15. The solvent solution of claim 10, said glycerol comprising about 5% by volume of said solvent solution.

16. The solvent solution of claim 8, said phenol comprising about 38% by volume of said solvent solution.

17. A method of isolating substantially pure RNA, DNA and proteins from biological tissue, comprising the steps of:

(a) homogenizing a tissue sample in the solvent solution of claim 1 to form a homogenate;

(b) adding a water-insoluble organic solvent to said homogenate and sedimenting to form a mixture consisting of an aqueous phase containing substantially pure, undegraded RNA, an organic phase containing proteins, and an interphase containing substantially pure, undegraded DNA;

(c) precipitating RNA from the aqueous phase by the addition of a lower alcohol thereto and recovering the precipitated RNA by sedimentation;

(d) precipitating proteins from the organic phase by the addition of a lower alcohol thereto and recovering the precipitated proteins by sedimentation; and

(e) recovering DNA from the interphase by washing the interphase with a predetermined amount of said solvent solution, sedimentation of the DNA and removal of any phenol and salt contamination from the DNA.

18. The method of claim 17 wherein said water-insoluble organic solvent added to said homogenate is chloroform.

19. The method of claim 17 wherein the lower alcohol added to the aqueous phase is isopropanol.

20. The method of claim 17 wherein the lower alcohol added to the organic phase is isopropanol.

21. A method of isolating substantially pure RNA, DNA and proteins from biological tissue, comprising the steps of:

(a) homogenizing a tissue sample in the solvent solution of claim 1 to form a homogenate;

(c) precipitating RNA from the aqueous phase by the addition of a lower alcohol thereto and recovering the precipitated RNA by sedimentation;

(d) extracting the organic phase and interphase with water;

(e) precipitating proteins from the organic phase by the addition of a lower alcohol thereto and recovering the precipitated proteins by sedimentation; and

(f) precipitating DNA from the interphase by the addition of CsCl, sodium citrate solution and a lower alcohol thereto and recovering the precipitated DNA by sedimentation.

22. The method of claim 21 wherein said water-insoluble organic solvent added to said homogenate is chloroform.

23. The method of claim 21 wherein the lower alcohol added to the aqueous phase is isopropanol.

24. The method of claim 21 wherein the lower alcohol added to the organic phase is isopropanol.

25. The method of claim 21 wherein the lower alcohol added to the interphase is ethanol.

26. A method of isolating substantially pure RNA, DNA and proteins from biological tissue, comprising the steps of:

(a) homogenizing a tissue sample in the solvent solution of claim 1 to form a homogenate;

(b) sedimenting substantially pure, undegraded DNA from said homogenate, washing the sedimented DNA with an amount of said solvent solution, and removing any phenol and salt contamination from the DNA;

(c) adding a water-insoluble organic solvent to the residual homogenate subsequent to said DNA sedimenting step, and thereafter sedimenting to form a mixture having an aqueous phase containing substantially pure, undegraded RNA and an organic phase containing proteins;

(d) precipitating RNA from the aqueous phase by the addition of a lower alcohol thereto and recovering the precipitated RNA by sedimentation;

(e) precipitating proteins from the organic phase by the addition of a lower alcohol thereto and recovering the precipitated proteins by sedimentation.

27. The method of claim 26 wherein said water-insoluble organic solvent added to said residual homogenate is chloroform.

28. The method of claim 26 wherein said lower alcohol added to the aqueous phase is isopropanol.

29. The method of claim 26 wherein said lower alcohol added to the organic phase is isopropanol.

30. A method of isolating substantially pure RNA, DNA and proteins from biological tissue, comprising the steps of:

(a) precipitating RNA from an aqueous phase obtained from a mixture consisting of an aqueous phase containing substantially pure, undegraded RNA, an organic phase containing proteins, and an interphase containing substantially pure, undegraded DNA, said mixture formed by adding a water-insoluble organic solvent to a homogenate and sedimenting, said homogenate formed by homogenizing a tissue sample in a solvent solution comprising effective amounts of phenol and a guanidinium compound for extracting substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from biological tissue, by the addition of a lower alcohol thereto and recovering the precipitated RNA by sedimentation;

(b) precipitating proteins from an organic phase obtained from a mixture consisting of an aqueous phase containing substantially pure, undegraded RNA, an organic phase containing proteins, and an interphase containing substantially pure, undegraded DNA, said mixture formed by adding a water-insoluble organic solvent to a homogenate and sedimenting, said homogenate formed by homogenizing a tissue sample in a solvent solution comprising effective amounts of phenol and a guanidinium compound for extracting substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from biological tissue, by the addition of a lower alcohol thereto and recovering the precipitated proteins by sedimentation; and

(c) recovering DNA from an interphase obtained from a mixture consisting of an aqueous phase containing substantially pure, undegraded RNA, an organic phase containing proteins, and an interphase containing substantially pure, undegraded DNA, said mixture formed by adding a water-insoluble organic solvent to a homogenate and sedimenting, said homogenate formed by homogenizing a tissue sample in a solvent solution comprising effective amounts of phenol and a guanidinium compound for extracting substantially pure and undegraded RNA, substantially pure and undegraded DNA, and proteins from biological tissue, by washing the interphase with a predetermined amount of said solvent solution, sedimentation of the DNA and removal of any phenol and salt contamination from the DNA.

Chimeric DNA-RNA catalytic sequences

2007-11-21T20:49:00.000-08:00

Abstract

This invention provides chimeric DNA/RNA catalytic molecules useful to cleave RNA sequences.

Patent number: 5149796
Filing date: Apr 30, 1991
Issue date: Sep 22, 1992
Inventors: John J. Rossi, Pairoj Chang, Bruce E. Kaplan
Assignee: City of Hope

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What is claimed is:

1. A catalytic molecule capable of cleaving an RNA sequence at a known ribozyme cleavage site said molecule having the formula

3' X - AAAG - Y - AGUAAGUC - Z 5'

3' X - CAAAG - Y - AGUAAGUC - Z 5'

in which X and Z are DNA sequences that base pair with an RNA substrate at positions juxtaposed to said known cleavage site,

AAAG, CAAAG and AGUAGUC are RNA sequences,

Y is a DNA sequence that base pairs inter se in a manner required to permit said RNA sequences to cleave said substrate at said cleavage site.

2. A catalytic molecule capable of cleaving an RNA sequence, said molecule having catalytic RNA moieties linked to first and second DNA moieties which base pair with the substrate RNA sequences flanking the cleavage site and interconnected by a third DNA sequence which base pairs inter se to facilitate said cleavage.

3. A molecule including the construct shown by FIG. 1 or FIG. 2.