Use of Hydroxylamine Derivates for Inhibiting Vitrectomy-Induced Cataracts
Methods to prevent, inhibit, or slow the development of vitrectomy-induced cataracts are disclosed. The methods comprise administering to the eye of a subject a composition comprising an opthalmologically acceptable carrier or diluent and at least one hydroxylamine compound in a therapeutically sufficient amount to prevent, inhibit, or slow the development of a vitrectomy-induced cataract in the subject to which the composition is administered.
1 . A method for inhibiting the development of a vitrectomy-induced cataract, comprising administering to the vitreous of a subject undergoing a vitrectomy a composition comprising an opthalmologically acceptable carrier or diluent and at least one hydroxylamine compound in a therapeutically sufficient amount to inhibit the development of a vitrectomy-induced cataract in the subject.
2 . The method of claim 1 , wherein the composition is administered before, during or after the vitrectomy is performed.
3 . The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 0.1 μM to about 10 mM.
4 . The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 1 μM to about 5 mM.
5 . The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 10 μM to about 2.5 mM.
6 . The method of claim 1 wherein the composition is administered to achieve in the vitreous tissue and fluids of the subject a concentration of about 50 μM to about 1 mM.
7 . The method of claim 1 wherein the composition is administered to achieve in the eye tissue and fluids of the subject a concentration of about 1 μM to about 100 μM.
8 . The method of claim 1 wherein the hydroxylamine compound is at least one of tempol-H, tempo-H, oxano-H, or a compound having the formula:
wherein 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, substituted alkyl, alkenyl, cycloalkyl, or heterocycle 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.
9 . The method of claim 8 wherein the hydroxylamine compound is 1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride.
10 . The method of claim 1 further comprising administering a reducing agent to the vitreous of the subject.
11 . The method of claim 10 , wherein the reducing agent is coadministered with the composition.
12 . The method of claim 10 , wherein the reducing agent is formulated as part of the composition.
13 . The method of claim 10 , wherein the reducing agent is administered separately from the composition.
14 . The method of claim 10 , wherein the reducing agent is a sulfhydryl compound.
15 . The method of claim 14 , wherein the reducing agent is mercaptopropionyl glycine, N-acetyl cysteine, β-mercaptoethylamine or glutathione.
16 . The method of claim 1 , wherein the composition is administered by injection.
17 . The method of claim 1 , wherein the composition is coadministered with irrigation solution during vitrectomy.
18 . The method of claim 1 , wherein the composition is formulated as part of the irrigation solution during vitrectomy.
19 . The method of claim 1 further comprising administering to the vitreous of the subject after said vitrectomy a composition comprising an opthalmologically acceptable carrier or diluent and at least one hydroxylamine compound in a therapeutically sufficient amount to inhibit the development of a vitrectomy-induced cataract in the subject.
20 . The method of claim 19 , wherein the composition administered after the vitrectomy is performed to achieve in the vitreous tissue and fluids of the subject a hydroxylamine concentration of about 0.1 μM to about 10 mM.
21 . The method of claim 19 , wherein the composition administered after the vitrectomy is injected into the vitreous.
22 . The method of claim 19 , wherein said composition administered after said vitrectomy is an eyewash, eye drop or ophthalmic ointment.
23 . The method of claim 19 , wherein the composition administered after said vitrectomy is administered from a polymeric disc or wafer placed on the surface of the eye.
24 . The method of claim 19 , wherein the hydroxylamine compound is tempol-H, tempo-H, oxano-H, or a compound having the formula:
wherein 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, substituted alkyl, alkenyl, cycloalkyl, or heterocycle 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.
25 . The method of claim 24 wherein a hydroxylamine compound is 1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride.