Retinopathy treatment
Inventors
BLANKS, Janet C. • Prentice, Howard Malcolm • Weissbach, Herbert
Assignees
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Publication Number
US-10792260-B2
Publication Date
2020-10-06
Expiration Date
Abstract
A method of preventing degeneration of photoreceptor cells in an eye of a mammalian subject includes the step of administering pharmaceutical composition comprising a sulindac agent to the eye of the subject.
Core Innovation
The invention relates to a method of treating oxidative stress-induced degeneration of photoreceptor cells and retinal pigment epithelial cells in an eye of a mammalian subject with dry macular degeneration. The method comprises administering an ophthalmically-acceptable pharmaceutical composition comprising a sulindac agent to the eye in an amount sufficient to reduce oxidative stress-induced degeneration of the photoreceptor cells and retinal pigment epithelial cells, where the degeneration is reduced after the administration step.
The described pharmaceutical composition comprises a sulindac agent, including sulindac, with additional composition features including a sterile aqueous buffer, dimethylsulfoxide, and a pH between 6.8 and 7.8. Administration modalities described for delivering the composition to the eye include topical eye drops, intravitreal injection, and slow-release depot devices.
A mechanistic basis is proposed for protection against oxidative insult-induced degeneration, involving PPAR and protein kinase C epsilon, with downstream protein kinase G, increased intracellular reactive oxygen species, and mitochondrial mK(ATP) channel opening to prevent mitochondrial permeability transition pore formation. The document describes experimental evidence showing dose-dependent protection against oxidative injury, pathway inhibition or reversal, ROS scavenging effects, mitochondrial KATP blockade effects, and upregulation of markers such as iNOS and Hsp27, together with histological and rhodopsin retention after light exposure.
Claims Coverage
The document includes one independent claim. The claim set covers treating oxidative stress-induced degeneration of photoreceptor cells and retinal pigment epithelial cells in a mammalian eye with dry macular degeneration by administering an ophthalmically-acceptable pharmaceutical composition comprising a sulindac agent, with dependent claim features refining composition components, pH, the specific sulindac agent identity, concentration, and administration modality.
Sulindac agent treatment of oxidative stress-induced degeneration in dry macular degeneration
A method of treating oxidative stress-induced degeneration of photoreceptor cells and retinal pigment epithelial cells in an eye of a mammalian subject with dry macular degeneration by administering an ophthalmically-acceptable pharmaceutical composition comprising a sulindac agent to the eye of the subject in an amount sufficient to reduce oxidative stress-induced degeneration of photoreceptor cells and retinal pigment epithelial cells in the eye of a mammalian subject, wherein the oxidative stress-induced degeneration is reduced after the step of administering the pharmaceutical composition.
Sulindac agent concentration range in the pharmaceutical composition
The method in which the pharmaceutical composition comprises the sulindac agent at between 0.001% to 3% by weight.
Sterile aqueous buffer and dimethylsulfoxide in the pharmaceutical composition
The method wherein the pharmaceutical composition includes a sterile aqueous buffer and dimethylsulfoxide.
Intravitreal injection administration route
The method that includes formulating a pharmaceutical composition for injection and administering it via intravitreal injection.
Specific sulindac agent identity as sulindac
The method in which the sulindac agent is sulindac.
Pharmaceutical composition pH range
The method using a pharmaceutical composition having a pH between 6.8 and 7.8.
Across the independent claim and its dependent refinements, coverage is directed to reducing oxidative stress-induced degeneration in dry macular degeneration by administering an ophthalmically-acceptable pharmaceutical composition containing a sulindac agent, with additional claim limitations concerning the sulindac agent form, concentration, pH, added components, and intravitreal injection as an administration route.
Stated Advantages
Reduces oxidative stress-induced degeneration of photoreceptor cells and retinal pigment epithelial cells in the eye of a mammalian subject with dry macular degeneration after administering the pharmaceutical composition.
Documented Applications
Treating oxidative stress-induced degeneration of photoreceptor cells and retinal pigment epithelial cells in an eye of a mammalian subject with dry macular degeneration.
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