Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension

Abstract

Disclosed is the use of cloprostenol and fluprostenol analogues in combination with carbonic anhydrase inhibitors for the treatment of glaucoma and ocular hypertension and ophthalmic compositions therefor.

1 - 15 . (canceled)  
     
     
         16 . A method of treating an optic nerve disorder, which comprises administering to the affected eye a composition comprising a therapeutically effective amount of a first compound selected from the group consisting of: beta blockers, carbonic anhydrase inhibitors, adrenergic agonists, and cholinergic agonists, and a second compound having the absolute stereochemical structure of the following formula (IV) and being substantially free of the enantiomer of said second compound:  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1 ═H; C 1 -C 12  straight-chain or branched alkyl; C 1 -C 12  straight-chain or branched acyl; C 3 -C 8  cycloalkyl; or a cationic salt moiety;  
 R 2 , R 3 ═H, or C 1 -C 5  straight-chain or branched alkyl; or R 2  and R 3  taken together may represent O;  
 X═O, S, or CH 2 ;  
 ═ represents any combination of a single bond, or a cis or trans double bond for the alpha (upper) chain; and a single bond or trans double bond for the omega (lower) chain;  
 R 9 ═H, C 1 -C 10  straight-chain or branched alkyl, or C 1 -C 10  straight-chain or branched acyl;  
 R 11 ═H, C 1 -C 10  straight-chain or branched alkyl, or C 1 -C 10  straight-chain or branched acyl;  
 Y═O; or H and OR 15  in either configuration wherein R 15 ═H, C 1 -C 10  straight-chain or branched alkyl, or C 1 -C 10  straight-chain or branched acyl; and  
 Z=Cl or CF 3 ;  
 with the proviso that when R 2  and R 3  taken together represent O, then R 1 ≠C 1 -C 12  straight-chain or branched acyl; and when R 2 ═R 3 ═H, then R 1 ≠a cationic salt moiety; and  
 with the further proviso that the following compound be excluded:  
 cyclopentane heptenol-5-cis-2-(3-αhydroxy-4-m-chlorophenoxy-1-trans-butenyl)-3,5 dihydroxy, [1 α , 2 β , 3 αa , 5 α ].  
 
     
     
         17 . The method of  claim 16 , wherein the first compound and the second compound are administered as a combination in an ophthalmically acceptable vehicle.  
     
     
         18 . The method of  claim 17 , wherein the first compound is a beta-blocker selected from the group consisting of: timolol, betaxolol, and levobunolol, and the second compound is fluprostenol and its pharmaceutically acceptable esters and salts.  
     
     
         19 . The method of  claim 17  , wherein the first compound is a carbonic anhydrase inhibitor that is brinzolamide, and the second compound is fluprostenol and its pharmaceutically acceptable esters and salts.  
     
     
         20 . The method of  claim 17 , wherein the first compound is an adrenergic agonist selected from the group consisting of: apraclonidine and brimonidine, and the second compound is fluprostenol and its pharmaceutically acceptable esters and salts.  
     
     
         21 . The method of  claim 20  wherein the first compound is brimonidine and the second compound is fluprostenol isopropyl ester.