Claims for Patent: 4,863,970

Summary for Patent: 4,863,970

Title:	Penetration enhancement with binary system of oleic acid, oleins, and oleyl alcohol with lower alcohols
Abstract:	Penetration-enhancing pharmaceutical compositions for topical transepidermal and percutaneous application are disclosed which are non-irritating to the skin. These compositions are made up of a safe and effective amount of an active pharmaceutical permeant, including hydrophilic salt forms, contained in a novel penetration-enhancing vehicle comprising, (i) 1-95% w. of a cell-envelope disordering compound selected from the group consisting of oleic acid, oleyl alcohol, glycerol monoleate, glycerol dioleate, glycerol trioleate and mixtures thereof, (ii) 5-75% w., and preferably 5-49% w., of a lower alkanol selected from the group consisting of ethanol, propanol and isopropanol and mixtures thereof and (iii) 0-45% w., and preferably 1-45% w., of an inert diluent which, according to properties of the permeant used, may range from hydrophilic to hydrophobic. Water, polyethylene or polypropylene glycols and mineral oil are exemplary diluents.
Inventor(s):	Patel; Dinesh C. (Murray, UT), Chang; Yunik (Lakewood, NJ)
Assignee:	Theratech, Inc. (Salt Lake City, UT)
Application Number:	07/218,702
Patent Claims:	1. A pharmaceutical composition for topical application having penetration-enhancing properties consisting essentially of: (a) a safe and effective amount of an active pharmaceutical agent contained in, (b) a penetration-enhancing vehicle exclusive of diols and N-cyclic solvents consisting essentially of: (i) 1-95% by weight of one or more cell-envelope disordering compounds selected from the group consisting of oleic acid, oleyl alcohol, glycerol esters of oleic acid and mixtures thereof; (ii) 5-75% by weight of a lower alkanol selected from the group consisting of ethanol, propanol and isopropanol and mixtures thereof; and (iii) 0-45% by weight of an inert diluent. 2. A composition according to claim 1 wherein the lower alkanol is present in amounts of between 5 and 49% by weight. 3. A composition according to claim 2 wherein the active pharmaceutical agent is present in amount ranging from about 0.01 to 50% by weight and the penetration enhancing vehicle is present in amounts ranging from about 50-99.99% by weight. 4. A composition according to claim 3 wherein the cell-envelope disordering compounds are members selected from the following groupings: (1) oleic acid and oleyl alcohol or mixtures thereof; (2) one or more glycerol esters of oleic acid; (3) oleic acid and one or more glycerol esters of oleic acid; (4) oleyl alcohol and one or more glycerols ester of oleic acid; and (5) mixtures of oleic acid and oleyl alcohol and one or more glycerol esters of oleic acid. 5. A composition according to claim 4 wherein the active pharmaceutical agent is present in amounts ranging from about 0.01 to 30% by weight and the penetration enhancing vehicle is present in amounts ranging from about 70 to 99.99% by weight. 6. A composition according to claim 5 wherein the cell-envelope disordering compound is a member selected from the group consisting of oleic acid and oleyl alcohol and mixtures thereof. 7. A composition according to claim 5 wherein the cell-envelope disordering compound is oleic acid. 8. A composition according to claim 6 wherein the cell-envelope disordering compound is oleyl alcohol. 9. A composition according to claim 5 wherein the cell-envelope disordering compound is a member selected from the group consisting of a one or more glycerol esters of oleic acid. 10. A composition according to claim 9 wherein the cell-envelope disordering compound is glycerol monooleate. 11. A composition according to claim 8 wherein the cell-envelope disordering compound is glycerol dioleate. 12. A composition according to claim 7 wherein the cell-envelope disordering compound is glycerol trioleate. 13. A composition according to claim 5 wherein the cell-envelope disordering compound is oleic acid admixed with a member selected from the group consisting of a one or more glycerol esters of oleic acid. 14. A composition according to claim 13 wherein the cell-envelope disordering compound is glycerol monooleate. 15. A composition according to claim 13 wherein the cell-envelope disordering compound is glycerol dioleate. 16. A composition according to claim 13 wherein the cell-envelope disordering compound is glycerol trioleate. 17. A composition according to claim 5 wherein the cell-envelope disordering compound is oleyl alcohol admixed with a member selected from the group consisting of a one or more glycerol esters of oleic acid. 18. A composition according to claim 17 wherein the cell-envelope disordering compound is glycerol monooleate. 19. A composition according to claim 17 wherein the cell-envelope disordering compound is glycerol dioleate. 20. A composition according to claim 17 wherein the cell-envelope disordering compound is glycerol trioleate. 21. A composition according to claim 5 wherein the alcohol is present in the penetration enhancer vehicle in amounts of between about 20 and 49% by weight. 22. A composition according to claim 4 wherein the inert diluent is present in the penetration enhancer vehicle in amounts ranging from 1 to 45% by weight. 23. A composition according to claim 22 wherein the active pharmaceutical agent is present in amounts ranging from about 0.01 to 30% by weight and the penetration enhancing is present in amounts ranging from about 70 to 99.99% by weight. 24. A composition according to claim 23 wherein the cell-envelope disordering compound is a member selected from the group consisting of oleic acid and oleyl alcohol and mixtures thereof. 25. A composition according to claim 24 wherein the cell-envelope disordering compound is oleic acid. 26. A composition according to claim 24 wherein the cell-envelope disordering compound is oleyl alcohol. 27. A method according to claim 23 wherein the cell-envelope disordering compound is a member selected from the group consisting of a one or more glycerol esters of oleic acid. 28. A composition according to claim 27 wherein the cell-envelope disordering compound is glycerol monooleate. 29. A composition according to claim 27 wherein the cell-envelope disordering compound is glycerol dioleate. 30. A composition according to claim 27 wherein the cell-envelope disordering compound is glycerol trioleate. 31. A composition according to claim 23 wherein the cell-envelope disordering compound is oleic acid admixed with a member selected from the group consisting of a one or more glycerol esters of oleic acid. 32. A composition according to claim 31 wherein the cell-envelope disordering compound is glycerol monooleate. 33. A composition according to claim 31 wherein the cell-envelope disordering compound is glycerol dioleate. 34. A composition according to claim 31 wherein the cell-envelope disordering compound is glycerol trioleate. 35. A composition according to claim 23 wherein the cell-envelope disordering compound is oleyl alcohol admixed with a member selected from the group consisting of a one or more glycerol esters of oleic acid. 36. A composition according to claim 35 wherein the cell-envelope disordering compound is glycerol monooleate. 37. A composition according to claim 35 wherein the cell-envelope disordering compound is glycerol dioleate. 38. A composition according to claim 35 wherein the cell-envelope disordering compound is glycerol trioleate. 39. A composition according to claim 23 wherein the inert diluent is a member selected from the group consisting of water, polypropylene glycol, polyethylene glycol, polyvinyl alcohols, polyvinylpyrrolidone, mineral oil, silicone oil, ethylene-vinyl acteate polymers or other suitable water or oil soluble low molecular weight polymers. 40. A composition according to claim 23 wherein the alcohol is present in the penetration enhancer combination in amounts between about 20 and 49% by weight.