Claims for Patent: 6,248,735

Summary for Patent: 6,248,735

Title:	Ophthalmic compositions comprising combinations of a carbonic anhydrase inhibitor and a .beta.-adrenergic antagonist
Abstract:	Combinations of a .beta.-adrenergic antagonist and a topical carbonic anhydrase inhibitor are particularly useful in the treatment of ocular hypertension, especially in patients insufficiently responsive to treatment with .beta.-adrenergic antagonists.
Inventor(s):	Baldwin; John J. (Gwynedd Valley, PA)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	08/833,067
Patent Claims:	1. A topical formulation for treatment of ocular hypertension or glaucoma comprising an opthalmologically acceptable carrier, 0.05 to 5% of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide, the individual diastereomers, enantiomers or mixtures thereof, or an ophthalmologically acceptable salt thereof, and 0.01 to 1.0% of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol, or an ophthalmologically acceptable salt thereof. 2. A formulation of claim 1 wherein the salt of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is maleate. 3. A formulation of claim 1 wherein the salt of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is the monohydrochloride salt. 4. A formulation of claim 3 wherein the concentration of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is 0.5 to 3%. 5. A formulation of claim 2 wherein the concentration of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is 0.1 to 0.5%. 6. A formulation of claim 1 wherein the concentration of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is 0.7 to 2.0% and the concentration of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is 0.5%. 7. A formulation of claim 6 which further contains a gum. 8. A formulation of claim 7 wherein the gum is gellan gum at a concentration of 0.1% to 2%. 9. A formulation of claim 1 which takes a form of solution, gel, ointment, suspension or solid insert. 10. A formulation of claim 6 wherein the ratio of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide to (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is greater than one. 11. A formulation of claim 10 wherein the concentration of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is 2% and (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is 0.5%. 12. A topical formulation for treatment of ocular hypertension or glaucoma comprising an opthalmologically acceptable carrier, 2% of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide monohydrochloride, and 0.5% of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol maleate, or an ophthalmologically acceptable salt thereof. 13. A formulation of claim 12 which further contains gellan gum at a concentration of 0.1% to 2%. 14. A method of treating ocular hypertension or glaucoma, which, comprises administration of an effective amount of a topical ophthalmic formulation to a patient in need thereof, comprising an ophthalmologically acceptable carrier, 0.05 to 5% of (S,S)-(-)-5,6dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-su lfonamide-7,7 dioxide, the individual diastereomers, enantiomers or mixtures thereof, or an ophthalmologically acceptable salt thereof, and 0.01 to 1.0% of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol, or an ophthalmologically acceptable salt thereof. 15. A method of claim 14 wherein the salt of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is maleate. 16. A method of claim 14 wherein the salt of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is the monohydrochloride salt. 17. A method of claim 16 wherein tie concentration of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is 0.5 to 3%. 18. A method of claim 15 wherein the concentration of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is 0.1 to 0.5%. 19. A method of claim 14 wherein the concentration of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is 0.7 to 2.0% and the concentration of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is 0.5%. 20. A method of claim 14 wherein the formulation contains a gum. 21. A method of claim 20 wherein the gum is gellan gum at a concentration of 0.1% to 2%. 22. A method of claim 14 wherein the formulation takes a form of solution, gel, ointment, suspension or solid insert. 23. A method of claim 14 wherein the formulation takes the form of a solution adapted for topical administration. 24. A method of claim 20 wherein the ratio of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-2,3-b]thiopyran-2-su lfonamide-7,7 dioxide to (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is greater than one. 25. A method of claim 14 wherein the concentration of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide is 2% and (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol is 0.5%. 26. A method of treating ocular hypertension or glaucoma, which comprises administration of an effective amount of a topical ophthalmic formulation to a patient in need thereof, comprising an ophthalmologically acceptable carrier, 2% of (S,S)-(-)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno-[2,3-b]thiopyran-2-s ulfonamide-7,7 dioxide monohydrochloride, 0.5% of (s)-(-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy-2-p ropanol maleate. 27. A method of claim 26 wherein the formulation contains gellan gum at a concentration of 0.1% to 2%.