Claims for Patent: 5,798,349

Summary for Patent: 5,798,349

Title:	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.
Inventor(s):	Julia Levy, Joan W. Miller, Evangelos S. Gradoudas, Tayyaba Hasan, Ursula Schmidt-Erfurth
Assignee:	Novelion Therapeutics Inc , Bausch Health Companies Inc , General Hospital Corp , Massachusetts Eye and Ear
Application Number:	US08/390,591
Patent Claims:	1. A method to treat conditions of the eye characterized by unwanted neovasculature, which method comprises:administering to a primate 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 the neovasculature with light from a laser, said light being absorbed by the green porphyrin so as to occlude said neovasculature. 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 FIG. 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 thereofwherein each of R1 and R2 is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and --CONR5 CO wherein R5 is aryl (6-10C) or alkyl (1-6C); each R3 is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C); R4 is --CH═CH2 or --CH(OR4')CH3 wherein R4' 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 FIG. 1-3 or 1-4 or a mixture thereof and wherein each of R1 and R2 is independently carbalkoxyl (2-6C);one R3 is carboxyalkyl (2-6C) and the other R3 is the ester of a carboxyalkyl (2-6C) substituent; and R4 is --CH═CH2 or --CH(OH)CH3. 6. The method of claim 5 wherein said green porphyrin is of the formula shown in FIG. 1-3 and wherein R1 and R2 are methoxycarbonyl;one R3 is --CH2 CH2 COOCH3 and the other R3 is --CH2 CH2 COOH; and R4 is --CH═CH2. 7. A method to treat unwanted choroidal neovasculature which method comprisesadministering to a primate 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 from a laser, said light being absorbed by the green porphyrin so as to occlude said neovasculature. 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 FIG. 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 thereofwherein each of R1 and R2 is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and --CONR5 CO wherein R5 is aryl (6-10C) or alkyl (1-6C); each R3 is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C); R4 is --CH═CH2 or --CH (OR4') CH3 wherein R4' 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 FIG. 1-3 or 1-4 or a mixture thereof and wherein each of R1 and R2 is independently carbalkoxyl (2-6C);one R3 is carboxyalkyl (2-6C) and the other R3 is the ester of a carboxyalkyl (2-6C) substituent; and R4 is --CH═CH2 or --CH(OH)CH3. 13. The method of claim 12 wherein said green porphyrin is of the formula shown in FIG. 1-3 andwherein R1 and R2 are methoxycarbonyl; one R3 is --CH2 CH2 COOCH3 and the other R3 is --CH2 CH2 COOH; and R4 is --CH═CH2. 14. A method to treat age-related macular degeneration (AMD) which method comprisesadministering to a primate 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 from a laser, said light being 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 FIG. 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 thereofwherein each of R1 and R2 is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and --CONR5 CO wherein R5 is aryl (6-10C) or alkyl (1-6C); each R3 is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C); R4 is --CH═CH2 or --CH(OR4') CH3 wherein R4' 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 FIG. 1-3 or 1-4 or a mixture thereof and wherein each of R1 and R2 is independently carbalkoxyl (2-6C);one R3 is carboxyalkyl (2-6C) and the other R3 is the ester of a carboxyalkyl (2-6C) substituent; and R4 is --CH═CH2 or --CH(OH)CH3. 20. The method of claim 19 wherein said green porphyrin is of the formula shown in FIG. 1-3 andwherein R1 and R2 are methoxycarbonyl; one R3 is --CH2 CH2 COOCH3 and the other R3 is --CH2 CH2 COOH; and R4 is --CH═CH2.