Amelioration of the development of cataracts and other ophthalmic diseases
View Patent ↗Ophthalmically acceptable compositions used in arresting the development of cataracts or macular degeneration comprising a pharmaceutically acceptable carrier or diluent and a compound having the formula: where R 1 and R 2 are, independently, H or C 1 to C 3 alkyl; R 3 and R 4 are, independently C 1 to C 3 alkyl; and where R 1 and R 2 , taken together, or R 3 and R 4 , taken together, or both may be cycloalkyl; R 5 is H, OH, or C 1 to C 6 alkyl; R 6 is or C 1 to C 6 alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl; R 7 is C 1 to C 6 alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl or where R 6 and R 7 , or R 5 , R 6 and R 7 , taken together, form a carbocycle or heterocycle having from 3 to 7 atoms in the ring.
1. A composition comprising a pharmaceutically acceptable carrier or diluent and a compound having the formula:
where R 1 and R 2 are, independently, H or C 1 to C 3 alkyl;
R 3 and R 4 are, independently, C 1 to C 3 alkyl; and
where R 1 and R 2 , taken together, or R 3 and R 4 , taken together, or both may be cycloalkyl;
R 5 is H, OH, or C 1 to C 6 alkyl;
R 6 is C 1 to C 6 alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl;
R 7 is C 1 to C 6 alkyl, alkenyl, alkynyl, or substituted alkyl or alkenyl;
or where R 6 and R 7 form a cycloalkyl having from 3 to 7 atoms in the ring.
2. The composition of claim 1 wherein the substituted alkyl or alkenyl has at least one alkoxy, alkylthio, alkylamino, dialkylamino, aryloxy, arylamino, benzyloxy, benzylamino or heterocyclic or YCO-Z where Y is O, N, or S and Z is alkyl, cycloalkyl or heterocyclic or aryl substituent.
3. The composition of claim 1 wherein R 6 and R 7 , taken together, are cyclopropyl.
4. The composition of claim 1 wherein each of R 1 through R 4 is C 1 to C 3 alkyl.
5. The composition of claim 1 wherein each of R 1 through R 4 is methyl.
6. The composition of claim 1 wherein R 6 is C 1 to C 6 alkyl substituted with at least one C 1 to C 6 alkoxy or benzyloxy group.
7. The composition of claim 1 wherein each of R 1 through R 4 is methyl, R 5 is H or methyl, R 6 is methyl substituted with benzyloxy or C 1 to C 6 alkoxy, and R 7 is methyl, or where R 6 and R 7 form a cyclopropyl group.
8. The composition of claim 1 wherein each of R 1 through R 4 is methyl, R 5 is methyl, R 6 is ethoxy methyl, and R 7 is methyl.
9. The composition of claim 1 wherein each of R 1 through R 4 is methyl, R 5 is methyl, R 6 is benzyloxy methyl, and R 7 is methyl.
10. The composition of claim 1 wherein each of R 1 through R 4 is methyl, R 5 is methyl, R 6 is hydroxymethyl, and R 7 is methyl.
11. The composition of claim 1 wherein each of R 1 through R 4 is methyl, R 5 is H and R 6 , and R 7 form a cyclopropyl ring.
12. The composition of claim 1 adapted for pharmaceutical use as an eye drop.
13. The composition of claim 1 further comprising a reducing agent.
14. The composition of claim 13 wherein the reducing agent is a sulfhydryl compound.
15. The composition of claim 1 further comprising mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione.
16. An ophthalmic composition comprising an ophthalmically acceptable carrier or diluent and a compound of claim 1 having an N-hydroxy piperidine portion bound to a solubility modifying portion, the compound having a solubility in water at 25° C. of at least about 0.25% by weight and a water n-octanol partition coefficient at 25° C. of at least about 5.
17. The composition of claim 16 wherein the N-hydroxy piperidine portion is cleaved from the compound under conditions found in the eye.
18. The composition of claim 16 wherein the N-hydroxy piperidine portion is cleaved from the compound under conditions found in the lens of the eye.
19. The composition of claim 16 wherein the N-hydroxy piperidine portion is cleaved enzymatically.
20. The composition of claim 16 wherein the N-hydroxy piperidine portion is 1,4-dihydroxy-2,2,6,6-tetramethylpiperidyl.
21. The composition of claim 16 further comprising a reducing agent.
22. The composition of claim 21 wherein the reducing agent is a sulfhydryl compound.
23. The composition of claim 16 further comprising mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione.