Retinoic acid derivatives in the treatment of acne

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

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

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,

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.

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

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.

Method and composition for treatment of acne vulgaris

Abstract

This invention relates to an improved method and composition for controlling all grades of acne vulgaris using a combination of sodium in the form of a pharmacologically acceptable sodium salt and an acne controlling compound selected from the group consisting of methyclothiazide, polythiazide and trichlormethazide, which is therapeutically effective in increasing sodium excretion in the sebaceous gland thereby controlling acne vulgaris eruptions. The conjoint use of the sodium salt and the acne controlling compound significantly reduces the unwanted side effects caused by the administration of the acne controlling compound including nausea, dizziness, hypotension and diuresis, which are experienced in some patients when the acne controlling compound is employed in acne treatment absent the conjoint use of the sodium salt.

Patent number: 4443442
Filing date: Dec 21, 1979
Issue date: Apr 17, 1984
Inventor: Scott D. Skillern

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What is claimed is:

1. A method for the treatment of acne vulgaris in a human having acne vulgaris which comprises conjointly administering an acne controlling compound induced side effect reducing amount comprising at least 0.2 grams of sodium in a form of a pharmacologically acceptable sodium salt and a therapeutically effective amount of an acne controlling compound selected from the group consisting of polythiazide and trichlormethiazide.

2. A method for the treatment of acne vulgaris in a human having acne vulgaris which comprises conjointly administering on a bi-daily basis an acne controlling compound induced side effect reducing amount comprising at least 0.2 grams of sodium in the form of a pharmacologically acceptable sodium salt and a therapeutically effective amount of an acne controlling compound selected from the group consisting of polythiazide and trichlormethiazide.

3. A pharmacological dose unit which is useful in the treatment of acne vulgaris in a human having acne vulgaris comprising in combination 0.2 grams to 0.8 grams of sodium in the form of a pharmacologically acceptable sodium salt and a therapeutically effective amount of an acne controlling compound selected from the group consisting of polythiazide and trichlormethiazide.

4. A pharmacological dose unit, as defined in claim 3, wherein the acne controlling compound is polythiazide in an amount of 0.5 to 5.0 mg.

5. A pharmacological dose unit, as defined in claim 3, wherein the acne controlling compound is trichlormethiazide in an amount from 0.5 to 5.0 mg.

Zinc methionine complex for acne treatment

Abstract

Novel pharmaceutical compositions containing 1:1 zinc methionine complex salts having the formula:

Patent number: 4039681
Filing date: Feb 23, 1976
Issue date: Aug 2, 1977
Inventor: Mahmoud M. Abdel-Monem
Assignee: Zinpro Corporation

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What is claimed is:

1. A composition for treating acne comprising a pharmaceutically acceptable carrier and a small but pharmaceutically effective acne alleviating amount of a 1:1 zinc methionine complexed salt of the formula:

[CH.sub.3 SCH.sub.2 CH.sub.2 CH(NH.sub.2)COO.Zn.sup.+.sup.+].sub.w X

wherein X is a non-toxic anion which has no inhibiting effect on the therapeutic effectiveness of said 1:1 zinc methionine complex, and W is an integer equal to the anionic charge of X.

2. The composition of claim 1 wherein said anion is an inorganic anion.

3. The composition of claim 2 wherein said compound is 1:1 zinc methionine acid sulfate.

4. The composition of claim 2 wherein said composition is in dosage form, with each dosage containing from about 50 milligrams to about 1500 milligrams of said 1:1 zinc methionine complex.

5. The composition of claim 4 wherein the dosage form of said 1:1 zinc methionine complex contains from about 100 milligrams to about 250 milligrams.

6. The composition of claim 4 wherein said carrier is an orally administrable liquid pharmaceutical carrier.

7. The composition of claim 4 wherein said carrier is an orally administrable water soluble solid pharmaceutical carrier.

8. A method of treating acne in a patient in need thereof which comprises orally administering to said patient a unit dosage of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a small but pharmaceutically effective acne alleviating amount of a 1:1 zinc methionine complex having the formula:

[CH.sub.3 SCH.sub.2 CH.sub.2 CH(NH.sub.2)COO.Zn.sup.+.sup.+].sub.w X

wherein X is a non-toxic inorganic anion inert to the pharmaceutical activity of the 1:1 zinc methionine complex and W is an integer equal to the anionic charge of X.

9. The method of claim 8 wherein said 1:1 zinc methionine complex is zinc methionine acid sulfate.

10. The method of claim 8 wherein said 1:1 zinc methionine complex is zinc methionine chloride.

Tretinoin in a gel vehicle for acne treatment

Abstract

An acne treatment gel composition, effective at low concentrations of tretinoin, is provided for topical application. The composition is highly effective in treating acne conditions and is capable of being stored without refrigeration for long periods of time without losing therapeutic effectiveness and while maintaining the uniformity and stability of the gel.

Patent number: 4247547
Filing date: Mar 19, 1979
Issue date: Jan 27, 1981
Inventor: Alan M. Marks
Assignee: Johnson & Johnson

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What is claimed is:

1. A gel formulation for topical application comprising from about 0.01% to about 0.025% by weight of said formulation of tretinoin; and a vehicle system consisting essentially of (a) from about 84 to about 99% by weight of said formulation of an organic solvent selected from the group consisting of ethanol, isopropanol, and propylene glycol; (b) an effective amount to inhibit oxidation of said tretinoin of a pharmaceutically acceptable antioxidant soluble in said organic solvent; and (c) an effective amount to cause gelling of hydroxypropyl cellulose.

2. The product of claim 1 wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, .alpha.-tocopherol, ascorbic acid, and propyl gallate.

3. The product of claim 2 which contains from about 0.01 to about 0.10% by weight of said antioxidant and from about 0.5 to about 5.0% by weight of said hydroxypropyl cellulose.

4. The product of claim 1 wherein said organic solvent comprises a mixture selected from the group consisting of ethanol and propylene glycol; isopropanol and proplyene glycol; and ethanol and isopropanol.

5. The product of claim 1 further comprising a dye.

6. The product of claim 1 further comprising a perfume oil.

7. The product of claim 1 further comprising a sunscreen.

8. The product of claim 1 further comprising an antimicrobial.

9. The product of claim 1 further comprising a topical corticosteroid.

10. A gel formulation for topical treatment of acne vulgaris consisting essentially of:

from about 0.01 to about 0.025% by weight of tretinoin;

from about 84 to about 99% by weight of an organic solvent selected from the group consisting of ethanol, isopropanol, propylene glycol and mixtures thereof;

from about 0.025 to about 0.075% by weight of an antioxidant selected from the group consisting of butylated hydroytoluene, butylated hydroxyanisole, ascorbic acid, propyl gallate, and .alpha.-tocopherol;

and from about 0.5 to about 3.0% of hydroxypropyl cellulose.

Tretinoin in a gel vehicle for acne treatment

Abstract

An acne treatment gel composition, effective at low concentrations of tretinoin, is provided for topical application. The composition is highly effective in treating acne conditions and is capable of being stored without refrigeration for long periods of time without losing therapeutic effectiveness and while maintaining the uniformity and stability of the gel.

Patent number: 4247547
Filing date: Mar 19, 1979
Issue date: Jan 27, 1981
Inventor: Alan M. Marks
Assignee: Johnson & Johnson

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What is claimed is:

1. A gel formulation for topical application comprising from about 0.01% to about 0.025% by weight of said formulation of tretinoin; and a vehicle system consisting essentially of (a) from about 84 to about 99% by weight of said formulation of an organic solvent selected from the group consisting of ethanol, isopropanol, and propylene glycol; (b) an effective amount to inhibit oxidation of said tretinoin of a pharmaceutically acceptable antioxidant soluble in said organic solvent; and (c) an effective amount to cause gelling of hydroxypropyl cellulose.

2. The product of claim 1 wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, .alpha.-tocopherol, ascorbic acid, and propyl gallate.

3. The product of claim 2 which contains from about 0.01 to about 0.10% by weight of said antioxidant and from about 0.5 to about 5.0% by weight of said hydroxypropyl cellulose.

4. The product of claim 1 wherein said organic solvent comprises a mixture selected from the group consisting of ethanol and propylene glycol; isopropanol and proplyene glycol; and ethanol and isopropanol.

5. The product of claim 1 further comprising a dye.

6. The product of claim 1 further comprising a perfume oil.

7. The product of claim 1 further comprising a sunscreen.

8. The product of claim 1 further comprising an antimicrobial.

9. The product of claim 1 further comprising a topical corticosteroid.

10. A gel formulation for topical treatment of acne vulgaris consisting essentially of:

from about 0.01 to about 0.025% by weight of tretinoin;

from about 84 to about 99% by weight of an organic solvent selected from the group consisting of ethanol, isopropanol, propylene glycol and mixtures thereof;

from about 0.025 to about 0.075% by weight of an antioxidant selected from the group consisting of butylated hydroytoluene, butylated hydroxyanisole, ascorbic acid, propyl gallate, and .alpha.-tocopherol;

and from about 0.5 to about 3.0% of hydroxypropyl cellulose.