Claims for Patent: 5,631,287

Summary for Patent: 5,631,287

Title:	Storage-stable prostaglandin compositions
Abstract:	The use of polyethoxylated castor oils in prostaglandin compositions greatly enhances the prostaglandin's chemical stability.
Inventor(s):	Schneider; L. Wayne (Crowley, TX)
Assignee:	Alcon Laboratories, Inc. (Fort Worth, TX)
Application Number:	08/362,677
Patent Claims:	1. A method of enhancing the chemical stability of an aqueous composition comprising a therapeutically-effective amount of a prostaglandin, wherein the method comprises adding a chemically-stabilizing amount of a polyethoxylated castor oil to the composition. 2. The method of claim 1 wherein the polyethoxylated castor oil is present at a concentration between about 0.02 wt % and about 20.0 wt %. 3. The method of claim 2 wherein the polyethoxylated castor oil is present at a concentration between about 0.1 wt % and about 5.0 wt %. 4. The method of claim 3 wherein the polyethoxylated castor oil is present at a concentration between about 0.5 wt % and about 2.0 wt %. 5. The method of claim 1 wherein the polyethoxylated castor oil is selected from the group consisting of: PEG-2 to PEG-200 castor oils and PEG-5 to PEG-200 hydrogenated castor oils. 6. The method of claim 5 wherein the polyethoxylated castor oil is selected from the group consisting of: PEG-15 to PEG-50 castor oils. 7. The method of claim 6 wherein the polyethoxylated castor oil is selected from the group consisting of: PEG-30 to PEG-35 castor oils. 8. The method of claim 1 wherein the prostaglandin is selected from the group consisting of: (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid t-butyl ester; (5Z)-(9S,11R,15R)-15-cyclohexyl-3-oxa-9,11,15-trihydroxy-16,17,18,19,20-pe ntanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R,15S)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid amide; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid N,N-dimethylamide; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid 1-methylcyclohexyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid 1-methylcyclopentyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid cyclopentyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid 2,2-dimethylpropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dLhydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid adamantyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid 2,6-diisopropylphenyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cydohexyl-11,15-dihydroxy-3-oxa-16,17,18,19, 20-pentanor-5-prostenoic acid 2,6-dimethylphenyl ester; (5Z, 13E)-(9S,11R,15R)-3-oxa-9,11,15-trihydroxy-16-(3-chlorophenoxy)-17,18,19,2 0-tetranor-5,13-prostadienoic acid isopropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-ll-hydroxy-15-methoxy-3-oxa-16,17 ,18, 19,20-pentanor-5-prostenoic acid t-butyl ester; (5Z)-(9R,11R,15R)-15-cyclohexyl-3-oxa-9,11,15-trihydroxy-16,17,18,19,20-pe ntanor-5-prostenoic acid isopropyl ester; (5E)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R)-9-chloro-15-cyclohexyl-11-dihydroxy-3-oxa-15-oxo-16,17,18,19 ,20-pentanor-5-prostenoic acid tertbutyl ester; (5Z)-(9S,11R,15R)-3-oxa-17-phenyl-9,11,15-trihydroxy-18,19,20-trinor-5-pro stenoic acid isopropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl1-(dimethylamino)-3-oxa-16,17,18,1 9,20-pentanor-5-prostene-11,15-diol; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenol; 9R,11R,15R)-9-chloro-15-cyclohexyl-11-dihydroxy-3-thia-16,17,18,19,20-pent anor-13-prostynoic acid; latanoprost (PhXA41); cloprostenol isopropyl ester; (5Z)-(9S,11R,15R)-1-decarboxy-1-(pivaloyloxy) methyl-9,11,15-trihydroxy-16-[(3-chlorophenyl)oxy]-17,18,19,20-tetranor-5- prostenoic acid; (5Z)-(9S,11R,15R)1-decarboxy-1-(pivaloyloxy)methyl-9,11,15-trihydroxy-16-[ (3-chlorophenyl)oxy]-17,18,19,20-tetranor-5,13-prostadienoic acid; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-16,17,18,19,20-pe ntanor-5-prostenoic acid isopropyl ester; (5Z)-(9S,11R,15S)-15-cyclohexy-9,11,15-trihydroxy-16,17,18,19,20-pentanor- 5-prostenoic acid isopropyl ester; (5Z, 13E)-(9S,11R,15R)-9,11,15-trihydroxy-16-(3-chlorophenoxy)-17,18,19,20-tetr anor-5,13-prostadienoic acid amide; PGF.sub.2.alpha. isopropyl ester; and fluprostenol isopropyl ester. 9. The method of claim 8 wherein the prostaglandin is selected from the group consisting of: (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid t-butyl ester; (5Z)-(9S,11R,15R)-15-cyclohexyl-3-oxa-9,11,15-trihydroxy-16,17,18,19,20-pe ntanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R,15S)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid isopropyl ester; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid amide; (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid N,N-dimethylamide; and (5Z)-(9R,11R,15R)-9-chloro-15-cydohexyl-11,15-dihydroxy-3-oxa-16,17,18,19, 20-pentanor-5-prostenoic acid 1-methylcyclohexyl ester. 10. The method of claim 9 wherein the prostaglandin is selected from the group consisting of (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid isopropyl ester and (5Z)-(9R,11R,15R)-9-chloro-15-cyclohexyl-11,15-dihydroxy-3-oxa-16,17,18,19 ,20-pentanor-5-prostenoic acid t-butyl ester. 11. The method of claim 1 wherein the prostaglandin is present at a concentration between about 0.0001 wt % and about 0.1 wt %. 12. The method of claim 1 wherein the composition is a topically administrable ophthalmic composition.