Amelioration Of The Development Of Cataracts And Other Ophthalmic Diseases
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 . An ophthalmic composition comprising an ophthalmically acceptable carrier or diluent and a compound 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-octonal partition coefficient at 25° C. of at least about 5.
2 . The composition of claim 1 wherein the N-hydroxy piperidine portion is cleaved from the compound under conditions found in the eye.
3 . The composition of claim 1 wherein the N-hydroxy piperidine portion is cleaved from the compound under conditions found in the lens of the eye.
4 . The composition of claim 1 wherein the N-hydroxy piperidine portion is cleaved enzymatically.
5 . The composition of claim 1 wherein the N-hydroxy piperidine portion is 1-oxyl-4-hydroxy-2,2,6,6-tetramethylpiperidyl.
6 . The composition of claim 1 further comprising a reducing agent.
7 . The composition of claim 6 wherein the reducing agent is a sulfhydryl compound.
8 . The composition of claim 1 further comprising mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione.
9 . A method of administering an antioxidant to a mammal comprising contacting the mammal with a composition comprising a pharmaceutically acceptable carrier or diluent and a compound 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-octonal partition coefficient at 25° C. of at least about 5.
10 . The method of claim 9 wherein the composition further comprises a reducing agent.
11 . The method of claim 9 further comprising coadministering a reducing agent to the patient.
12 . The method of claim 11 wherein the reducing agent is a sulfhydryl compound.
13 . The method of claim 9 further comprising coadministering mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione to the patient.
14 . The method of claim 11 wherein the coadministration is via eye drops or eye wash.
15 . The method of claim 9 wherein the contact is made via eye drops; eye wash; aerosol; enema or suppositories; oral tablets; liquids and sprays; intravenous, subcutaneous, and intraperitoneal injections; or application to the skin as a patch or ointment.
16 . A method for identifying a pharmaceutical for delivery to the eye of a patient in the form of eye drops comprising selecting a compound having a water solubility at 25° C. of at least about 0.25% by weight and a water-n-octonal partition coefficient of at least about 5 at 25° C., which compound is enzymatically cleavable under conditions obtained in the lens of the eye of a patient to give rise to an N-hydroxy piperidine.
17 . The method of claim 16 further comprising coadministering a reducing agent to the patient.
18 . The method of claim 17 wherein the reducing agent is a sulfhydryl compound.
19 . The method of claim 16 further comprising coadministering mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione to the patient.
20 . A method of administering an antioxidant to a mammal comprising contacting the mammal with a composition comprising a pharmaceutically acceptable carrier or diluent with 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.
21 . The method of claim 20 wherein said composition is ophthalmically acceptable.
22 . The method of claim 20 further comprising coadministering a reducing agent to the patient.
23 . The method of claim 22 wherein the reducing agent is a sulfhydryl compound.
24 . The method of claim 20 further comprising coadministering mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione to the patient.
25 . The method of claim 22 wherein the coadministration is via eye drops or eye wash.
26 . The method of claim 20 wherein the contact is made via eye drops; eye wash; aerosol; enema or suppositories; oral tablets; liquids and sprays; intravenous, subcutaneous, and intraperitoneal injections; or application to the skin as a patch or ointment.
27 . A method of ameliorating the development of a cataract in the eye of a patient comprising administering to the eye of such patient an ophthalmic composition comprising an ophthalmically acceptable carrier or diluent containing 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 , or R 5 , R 6 and R 7 , taken together, form a carbocycle or heterocycle having from 3 to 7 atoms in the atoms.
28 . The method of claim 27 further comprising coadministering a reducing agent to the patient.
29 . The method of claim 28 wherein the reducing agent is a sulfhydryl compound.
30 . The method of claim 27 further comprising coadministering mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione to the patient.
31 . The method of claim 28 wherein the coadministration is via eye drops or eye wash.
32 . A method of ameliorating the development of a cataract in the eye of a patient comprising administering to the eye of such patient an ophthalmic composition comprising an ophthalmically acceptable carrier or diluent and a compound 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-octonal partition coefficient at 25° C. of at least about 5.
33 . The method of claim 32 further comprising coadministering a reducing agent to the patient.
34 . The method of claim 33 wherein the reducing agent is a sulfhydryl compound.
35 . The method of claim 32 further comprising coadministering mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione to the patient.
36 . The method of claim 33 wherein the coadministration is via eye drops or eye wash.
37 . A method of treating macular degeneration in the lens of a patient comprising administering to the eye of such patient an ophthalmologic composition comprising an ophthalmically acceptable carrier or diluent in the form of eye drops containing 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.
38 . The method of claim 37 further comprising coadministering a reducing agent to the patient.
39 . The method of claim 38 wherein the reducing agent is a sulfhydryl compound.
40 . The method of claim 37 further comprising coadministering mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine, or glutathione to the patient.
41 . The method of claim 37 wherein the coadministration is via eye drops or eye wash.