METHODS AND POLYMER COMPOSITIONS FOR TREATING RETINAL DETACHMENT AND OTHER OCULAR DISORDERS
The invention provides methods and polymer compositions for treating retinal detachment and other ocular disorders, where the methods employ polymer compositions that can form a hydrogel in the eye of a subject. The hydrogel is formed by reaction of (i) a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R 1 —SH wherein R 1 is an ester-containing linker, such as a thiolated poly(vinyl alcohol) polymer and (ii) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups.
1 - 127 . (canceled)
128 . An injectable, ocular formulation for forming a hydrogel in an eye of a subject, the formulation comprising:
a. a nucleo-functional polymer that is a biocompatible polymer comprising poly(vinyl alcohol) containing a plurality of thio-functional groups —R 1 —SH, wherein R 1 is an ester-containing linker;
b. an electro-functional polymer that is a biocompatible polymer comprising poly(ethylene glycol) containing at least one thiol-reactive group; and
c. a liquid pharmaceutically acceptable carrier suitable for administration of the ocular formulation to the eye of the subject;
wherein the ocular formulation has an osmolality in the range of about 280 mOsm/kg to about 315 mOsm/kg and the formulation forms a hydrogel in the eye of the subject.
129 . The formulation of claim 128 , wherein the formulation has an osmolality in the range of about 280 mOsm/kg to about 300 mOsm/kg.
130 . The formulation claim 128 , further comprising an alkali metal salt.
131 . The formulation of claim 128 , further comprising sodium chloride, potassium chloride, calcium chloride, magnesium chloride, or a combination of two or more of the foregoing.
132 . The formulation of claim 128 , wherein the formulation contains water, and the formulation has a pH in the range of about 7.1 to about 7.7.
133 . The formulation of claim 132 , wherein the formulation has a pH in the range of about 7.3 to about 7.5.
134 . The formulation of claim 128 , wherein the formulation has a viscosity within 300% of water.
135 . The formulation of claim 128 , wherein the formulation has a viscosity in the range of 0.004 Pa*s to 0.5 Pa*s.
136 . The formulation of claim 128 , wherein the formulation has a viscosity such that it can be administered through a needle having a gauge of less than or equal to 23 using a force of no more than 5N.
137 . The formulation of claim 128 , wherein the formulation is formed following separate injection of the nucleo-functional polymer and the electro-functional polymer into the vitreous cavity of the eye of the subject.
138 . The formulation of claim 128 , wherein the nucleo-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol and the electro-functional polymer has a weight-average molecular weight in the range of from about 500 g/mol to about 1,000,000 g/mol.
139 . The formulation of claim 128 , wherein the mole ratio of the plurality of thio-functional groups-R 1 —SH to the at least one thiol-reactive group is in the range of 10:1 to 1:10, 5:1 to 1:1, or 2:1 to 1:1.
140 . The formulation of claim 128 , wherein R 1 —SH is —OC(O)—(C 1 -C 6 alkylene)-SH.
141 . The formulation of claim 128 , wherein the poly(ethylene glycol) is linear, branched, a dendrimer, or multi-armed.
142 . The formulation of claim 128 , wherein the hydrogel formed in the eye of the subject has a refractive index in the range of from about 1.2 to about 1.5.
143 . The formulation of claim 128 , wherein the hydrogel formed in the eye of the subject has a transparency of at least 90% for light in the visible spectrum when measured through the hydrogel having a thickness of 2 cm.
144 . The formulation of claim 128 , wherein the hydrogel formed in the eye of the subject has a gelation time of less than about 10 minutes.
145 . The formulation of claim 128 , wherein the hydrogel formed in the eye of the subject undergoes complete biodegradation from the eye of the subject within about 3 days to about 7 days, about 2 weeks to about 8 weeks, about 4 months to about 6 months, or within 12 months or 24 months.
146 . The formulation of claim 128 , wherein the hydrogel formed in the eye of the subject has a biodegradation half-life in the range of from about 1 week to about 3 weeks or from about 8 weeks to about 15 weeks when disposed within the vitreous cavity of an eye.
147 . The formulation of claim 128 , wherein the hydrogel formed in the eye of the subject generates a pressure within the eye of less than 25 mmHg.