Use of green porphyrins to treat neovasculature in the eye

Abstract

Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.

1 . A method to treat conditions of the eye characterized by unwanted neovasculature, which method comprises: 
 administering to a subject in need of such treatment an amount of liposomal formulation of green porphyrin sufficient to permit an effective amount to localize in said neovasculature;    permitting sufficient time to elapse to allow an effective amount of said green porphyrin to localize in said neovasculature; and    irradiating neovasculature with light absorbed by the green porphyrin.    
     
     
         2 . The method of  claim 1  wherein the neovasculature is choroidal neovasculature.  
     
     
         3 . The method of  claim 1  wherein the green porphyrin is of the formula shown in FIGS.  1 - 3  or  1 - 4 .  
     
     
         4 . The method of  claim 1  wherein said green porphyrin is of a formula shown in FIG. 1 or a mixture thereof 
 wherein each of R 1  and R 2  is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and —CONR 5 CO wherein R 1  is aryl (6-10C) or alkyl (1-6C);  
 each R 3  is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C);  
 R 4  is CH═CH 2  or —CH(OR 4. )CH 3  wherein R 4.  is H, or alkyl (1-6C) optionally substituted with a hydrophilic substituent.  
 
     
     
         5 . The method of  claim 4  wherein said green porphyrin is of the formula shown in FIGS.  1 - 3  or  1 - 4  or a mixture thereof and wherein each of R 1  and R 2  is independently carbalkoxyl (2-6C); 
 one R 3  is carboxyalkyl (2-6C) and the other R 3  is the ester of a carboxyalkyl (2-6C) substituent; and  
 R 4  is CH═CH 2  or —CH(OH)CH 3 .  
 
     
     
         6 . The method of  claim 5  wherein said green porphyrin is of the formula shown in FIGS.  1 - 3  and 
 wherein R 1  and R 2  are methoxycarbonyl;  
 one R 3  is —CH 2 CH 2 COOCH 3  and the other R 3  is CH 2 CH 2 COOH; and  
 R 4  is CH═CH 2 .  
 
     
     
         7 . A method to treat unwanted choroidal neovasculature ,which method comprises 
 administering to a subject in need of such in need of such treatment an amount of green porphyrin sufficient to permit an effective amount to localize in said choroidal neovasculature;    permitting sufficient time to elapse to allow an effective amount of said green porphyrin to localize in said choroidal neovasculature; and    irradiating said choroidal neovasculature with light absorbed by the green porphyrin.    
     
     
         8 . The method of  claim 7  wherein said green porphyrin is complexed with low-density lipoprotein.  
     
     
         9 . The method of  claim 7  wherein said green porphyrin is contained in a liposomal preparation.  
     
     
         10 . The method of  claim 7  wherein the green porphyrin is of the formula shown in FIGS.  1 - 3  or  1 - 4 .  
     
     
         11 . The method of  claim 7  wherein said green porphyrin is of a formula shown in FIG. 1 or a mixture thereof 
 wherein each of R 1  and R 2  is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and —CONR 5 CO wherein R 5  is aryl (6-10C) or alkyl (1-6C);  
 each R 3  is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C);  
 R 4  is CH═CH 2  or —CH(OR 4. )CH 3  wherein R 4.  is H or alkyl (1-6C) optionally substituted with a hydrophilic substituent.  
 
     
     
         12 . The method of  claim 11  wherein said green porphyrin is of the formula shown in FIGS.  1 - 3  or  1 - 4  or a mixture thereof and wherein each of R 1  and R 2  is independently carbalkoxyl (2-6C); 
 one R 3  is carboxyalkyl (2-6C) and the other R 3  is the ester of a carboxyalkyl (2-6C) substituent; and  
 R 4  is CH═CH 2  or —CH(OH)CH 3 .  
 
     
     
         13 . The method of  claim 12  wherein said green porphyrin is of the formula shown in FIGS.  1 - 3  and 
 wherein R 1  and R 2  are methoxycarbonyl;  
 one R 3  is —CH 2 CH 2 COOCH 3  and the other R 3  is CH 2 CH 2 COOH; and  
 R 4  is CH═CH 2 .  
 
     
     
         14 . A method to treat age-related macular degeneration (AMD) which method comprises 
 administering to a subject in need of such treatment an amount of green porphyrin sufficient to permit an effective amount to localize in the choroid;    permitting sufficient time to elapse to allow an effective amount of said green porphyrin to localize in said choroid; and    irradiating said choroid with light absorbed by the green porphyrin.    
     
     
         15 . The method of  claim 14  wherein said green porphyrin is complexed with low-density lipoprotein.  
     
     
         16 . The method of  claim 14  wherein said green porphyrin is contained in a liposomal preparation.  
     
     
         17 . The method of  claim 14  wherein the green porphyrin is of the formula shown in FIGS.  1 - 3  or  1 - 4 .  
     
     
         18 . The method of  claim 14  wherein said green porphyrin is of a formula shown in FIG. 1 or a mixture thereof 
 wherein each of R 1  and R 2  is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and —CONR 5 CO wherein R 5  is aryl (6-10C) or alkyl (1-6C);  
 each R 3  is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C);  
 R 4  is CH═CH 2  or —CH(OR 4. )CH 3  wherein R 4.  is H, or alkyl (1-6C) optionally substituted with a hydrophilic substituent.  
 
     
     
         19 . The method of  claim 18  wherein said green porphyrin is of the formula shown in FIGS.  1 - 3  or  1 - 4  or a mixture thereof and wherein each of R 1  and R 2  is independently carbalkoxyl (2-6C); 
 one R 3  is carboxyalkyl (2-6C) and the other R 3  is the ester of a carboxyalkyl (2-6C) substituent; and  
 R 4  is CH═CH 2  or —CH(OH)CH 3 .  
 
     
     
         20 . The method of  claim 19  wherein said green porphyrin is of the formula shown in FIGS.  1 - 3  and 
 wherein R 1  and R 2  are methoxycarbonyl;  
 one R 3  is —CH 2 CH 2 COOCH 3  and the other R 3  is CH 2 CH 2 COOH; and  
 R 4  is CH═CH 2 .