Retinal derivatives and methods for the use thereof for the treatment of visual disorders

Abstract

Compositions of and methods for using synthetic retinal derivatives as retinoid replacements and opsin agonists are provided.

What is claimed is: 
     
         1 . A retinyl ester selected from the group consisting of a 9-cis-retinyl ester and an 11-cis-retinyl ester, wherein the ester substituent comprises a carboxylate radical of a C 3  to C 22  polycarboxylic acid, with the proviso that the ester substituent is not tartrate. 
     
     
         2 . The retinyl ester of  claim 1 , which is a 9-cis-retinyl ester of a C 3  to C 22  polycarboxylate. 
     
     
         3 . The retinyl ester of  claim 1 , which is a 9-cis-retinyl ester of a C 3  to C 10  polycarboxylate. 
     
     
         4 . The retinyl ester of  claim 3 , wherein the 9-cis-retinyl ester is 9-cis-retinyl succinate, 9-cis-retinyl citrate, 9-cis-retinyl ketoglutarate, 9-cis-retinyl fumarate, 9-cis-retinyl malate or 9-cis-retinyl oxaloacetate. 
     
     
         5 . The retinyl ester of  claim 1 , which is an 11-cis-retinyl ester of a C 3  to C 22  polycarboxylate. 
     
     
         6 . The retinyl ester of  claim 1 , which is an 11-cis-retinyl ester of a C 3  to C 10  carboxylate. 
     
     
         7 . The retinyl ester of  claim 6 , wherein the 11-cis-retinyl ester is 11-cis-retinyl succinate, 11-cis-retinyl citrate, 11-cis-retinyl ketoglutarate, 11-cis-retinyl fumarate, 11-cis-retinyl malate or 11-cis-retinyl oxaloacetate. 
     
     
         8 . A pharmaceutical composition comprising the retinyl ester of  claim 1  and a pharmaceutically acceptable vehicle. 
     
     
         9 . A pharmaceutical composition of  claim 8 , compounded as an opthalmological composition in an opthalmologically acceptable vehicle for administration to the eye topically or by intra-ocular injection. 
     
     
         10 . A method of restoring photoreceptor function in a mammal, comprising administering to a mammalian subject having an endogenous retinoid deficiency an effective amount of a synthetic retinal derivative, wherein the synthetic retinal derivative is converted into a retinal capable of forming a functional opsin/retinal complex,
 wherein the synthetic retinal derivative is a 9-cis-retinyl ester, an 11-cis-retinyl ester, or a combination thereof;   wherein the ester substituent comprises a carboxylate radical of a C 1 -C 10  monocarboxylic acid or a C 2  to C 22  polycarboxylic acid.   
     
     
         11 . The method of  claim 10 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate or 11-cis-retinyl acetate. 
     
     
         12 . The method of  claim 10 , wherein the ester substituent comprises a carboxylate radical of a polycarboxylic acid of C 3  to C 10 . 
     
     
         13 . The method of  claim 12 , wherein the ester substituent is selected from the group consisting of succinate, citrate, ketoglutarate, fumarate, malate and oxaloacetate. 
     
     
         14 . The method of  claim 10 , wherein the mammalian subject is human. 
     
     
         15 . A method of ameliorating loss of photoreceptor function in a mammal, comprising: administering an effective amount of a synthetic retinal derivative to the vertebrate eye, wherein the synthetic retinal derivative is converted into a retinal capable of forming a functional opsin/retinal complex,
 wherein the synthetic retinal derivative is a 9-cis-retinyl, an 11-cis-retinyl ester, or a combination thereof;   wherein the ester substituent comprises a carboxylate radical of a C 1 -C 10  monocarboxylic acid or a C 2  to C 22  polycarboxylic acid.   
     
     
         16 . The method of  claim 15 , wherein the synthetic retinal derivative is 9-cis-retinyl acetate or 11-cis-retinyl acetate. 
     
     
         17 . The method of  claim 15 , wherein the ester substituent comprises a carboxylate radical of a polycarboxylic acid of C 3  to C 10 . 
     
     
         18 . The method of  claim 17 , wherein the ester substituent is selected from the group consisting of succinate, citrate, ketoglutarate, fumarate, malate and oxaloacetate.