Claims
- 1. A method for treating the epidermis of a terrestrial mammalian subject suffering from hyperkeratosis, visible scale or both due to increased intercellular cohesion of the stratum corneum, said method comprising administering to said epidermis a topical composition comprising an active ingredient that neutralizes the pH of the stratum corneum and is a member selected from the group consisting of inhibitors of proton pumps, transporters or antiporters, inhibitors of free fatty acid generation from complex lipids, inhibitors of proteolytic processes that generate organic acids and buffers with a pH of 7.0 or greater, said active ingredient being present in a concentration that is effective in raising the pH of said epidermis thereby reducing intercellular cohesion and resulting in easier detachment of normal stratum corneum and easier removal of hyperkeratotic stratum corneum.
- 2. A method in accordance with claim 1 in which said active ingredient is an inhibitor of proton pumps, transporters or antiporters.
- 3. A method in accordance with claim 2 in which said inhibitor is a an inhibitor of NHE1.
- 4. A method in accordance with claim 2 in which said inhibitor is a a member selected from the group consisting of amiloride, dimethylamiloride, ethylisopropylamiloride, methylpropylamiloride, methylisobutylamiloride, hexametyleneamiloride, HOE694 and HOE642.
- 5. A method in accordance with claim 2 in which said inhibitor is amiloride.
- 6. A method in accordance with claim 2 in which said inhibitor is HOE694.
- 7. A method in accordance with claim 1 in which said active ingredient is an inhibitor of free fatty acid generation from complex lipids.
- 8. A method in accordance with claim 7 in which said inhibitor is an inhibitor of phospholipase A2.
- 9. A method in accordance with claim 7 in which said inhibitor is a member selected from the group consisting of bromphenacyl bromide, 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, quinacrine and mepacrine.
- 10. A method in accordance with claim 7 in which said inhibitor is bromphenacyl bromide.
- 11. A method in accordance with claim 7 in which said inhibitor is 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol.
- 12. A method in accordance with claim 7 in which said inhibitor is an inhibitor of β-glucocerebrosidase.
- 13. A method in accordance with claim 7 in which said inhibitor is a member selected from the group consisting of bromconduritol-β-epoxide.
- 14. A method in accordance with claim 1 in which said active ingredient is an inhibitor of proteolytic processes that lead to the generation organic acids.
- 15. A method in accordance with claim 14 in which said inhibitor is an inhibitor which blocks proteolytic processes that breakdown filaggrin.
- 16. A method in accordance with claim 1 in which said inhibitor is an inhibitor which blocks processes that generate urocanic acid.
- 17. A method in accordance with claim 16 in which said inhibitor is a member selected from the group consisting of histidase inhibitors.
- 18. A method in accordance with claim 16 in which said inhibitor is nitromethane or histidinol phosphate.
- 19. A method in accordance with claim 1 in which said active ingredient is a buffer solution with a pH 7.0 or greater.
- 20. A method in accordance with claim 19 in which said buffer solution is a member selected from the group consisting of solutions of HEPES-based, MES-based, MOPS-based, PIPES-based, TES-based, phosphate-based, citrate-based or bicarbonate-based buffers.
- 21. A method in accordance with claim 19 in which said buffer solution is a solution of a HEPES-based buffer.
- 22. A method in accordance with claim 19 in which said buffer solution is a solution with a pH range of 7.0-8.0.
- 23. A method in accordance with claim 19 in which said buffer solution is a pH 7.4 buffer.
- 24. A method in accordance with claim 1 in which said topical composition comprises two or more of said active ingredients.
- 25. A method for manipulating the epidermis of a terrestrial mammalian subject with the purpose of providing improved transdermal delivery of co- or sequentially applied drugs or nutrients for systemic, regional or local applications, said method comprising administering to said epidermis a topical composition comprising an active ingredient that neutralizes the pH of the stratum corneum and is a member selected from the group consisting of inhibitors of proton pumps, transporters or antiporters, inhibitors of free fatty acid generation from complex lipids, inhibitors of proteolytic processes that generate organic acids, and buffers with a pH of 7.0 or greater, said active ingredient being present in a concentration that is effective at raising the pH of said epidermis with the purpose of reducing intercellular cohesion and integrity of the stratum corneum to breakdown the epidermal permeability barrier.
- 26. A method in accordance with claim 25 in which said active ingredient is an inhibitor of proton pumps, transporters or antiporters.
- 27. A method in accordance with claim 26 in which said inhibitor is a an inhibitor of NHE1.
- 28. A method in accordance with claim 26 in which said inhibitor is a a member selected from the group consisting of amiloride, dimethylamiloride, ethylisopropylamiloride, methylpropylamiloride, methylisobutylamiloride, hexametyleneamiloride, HOE694 and HOE642.
- 29. A method in accordance with claim 26 in which said inhibitor is amiloride.
- 30. A method in accordance with claim 26 in which said inhibitor is HOE694.
- 31. A method in accordance with claim 25 in which said active ingredient is an inhibitor of free fatty acid generation from complex lipids.
- 32. A method in accordance with claim 31 in which said inhibitor is an inhibitor of phospholipase A2.
- 33. A method in accordance with claim 31 in which said inhibitor is a member selected from the group consisting of bromphenacyl bromide, 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, quinacrine and mepacrine.
- 34. A method in accordance with claim 31 in which said inhibitor is bromphenacyl bromide.
- 35. A method in accordance with claim 31 in which said inhibitor is one hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol.
- 36. A method in accordance with claim 31 in which said inhibitor is an inhibitor of β-glucocerebrosidase.
- 37. A method in accordance with claim 31 in which said inhibitor is a member selected from the group consisting of bromconduritol-β-epoxide.
- 38. A method in accordance with claim 25 in which said active ingredient is an inhibitor of proteolytic processes that lead to the generation organic acids.
- 39. A method in accordance with claim 38 in which said inhibitor is an inhibitor which blocks proteolytic processes that break down filaggrin.
- 40. A method in accordance with claim 25 in which said inhibitor is an inhibitor which blocks processes that generate urocanic acid.
- 41. A method in accordance with claim 40 in which said inhibitor is a member selected from the group consisting of histidase inhibitors.
- 42. A method in accordance with claim 40 in which said inhibitor is nitromethane or histidinol phosphate.
- 43. A method in accordance with claim 25 in which said active ingredient is a buffer solution with a pH 7.0 or greater.
- 44. A method in accordance with claim 43 in which said buffer solution is a member selected from the group consisting of solutions of HEPES-based, MES-based, MOPS-based, PIPES-based, TES-based, phosphate-based, citrate-based or bicarbonate-based buffers.
- 45. A method in accordance with claim 43 in which said buffer solution is a solution of a HEPES-based buffer.
- 46. A method in accordance with claim 43 in which said buffer solution is a solution with a pH range of 7.0-8.0.
- 47. A method in accordance with claim 43 in which said buffer solution is a pH 7.4 buffer.
- 48. A method in accordance with claim 25 in which said topical composition comprises two or more of said active ingredients
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[0001] This invention was made at least in part with assistance from the United States Federal Government, under Grant No. AR 19098 of the National Institutes of Health. As a result, the government has certain rights in this invention.