CA-3062170-C - METHODS AND COMPOSITIONS FOR IMPROVING EYE HEALTH

CA3062170CCA 3062170 CCA3062170 CCA 3062170CCA-3062170-C

Abstract

Provided herein are anti-aging compositions and methods for maintaining and/or improving eye health in a subject, comprising administering to the eye of the subject a therapeutically effective amount of a compound that modulates the ATP-sensitive K+ channel and a pharmaceutically acceptable carrier. A method of treating glaucoma in a patient, comprising: obtaining a biological sample from the patient; testing the biological sample for presence of a mutation in Kir6.2 protein or KCNJ11 gene; and provided that the biological sample tests positive for the presence of a mutation in Kir6.2 protein or KCNJ11 gene, administering to the patient a therapeutically effective amount of a compound that specifically inhibits the Kir6.2 ATP-sensitive K+ channel and a pharmaceutically acceptable carrier.

Inventors

Nino Sorgente
Gabriele Thumann

Assignees

Nino Sorgente
Gabriele Thumann

Dates

Publication Date: 20260505
Application Date: 20180503
Priority Date: 20170505

Claims (2)

CLAIMS 1. Use of a composition comprising tolbutamide, or a pharmaceutically acceptable salt or solvate thereof, and an ophthalmically acceptable carrier for treating glaucoma in a patient that expresses a mutated Kir6.2 ATP sensitive K+ channel protein, wherein the tolbutamide, or a pharmaceutically acceptable salt or solvate thereof increases aqueous humor outflow, and wherein the composition is for ocular administration. 2. Use of a composition comprising tolbutamide, or a pharmaceutically acceptable salt or solvate thereof, and an ophthalmically acceptable carrier for increasing aqueous humor outflow via the ciliary body/trabecular meshwork/ Schlemm’s canal complex in an eye of a glaucoma patient that expresses a mutated Kir6.2 ATP sensitive K+ channel protein, wherein the composition is for ocular administration. 3. The use of claim 1 or 2, wherein the mutated Kir6.2 ATP sensitive K+ channel protein has a V337I mutation. 4. The use of claim 3, wherein the V337I mutation is caused by a nonsense mutation, rs5215, in the KCN11 gene. 5. The use of claim 1 or 2, wherein the mutated Kir6.
2 ATP sensitive K+ channel protein has a E23K mutation. 6. The use of claim 5, wherein the E23K mutation is caused by a nonsense mutation, rs5219, in the KCN11 gene. 7. The use of any one of claims 1 to 6, wherein the patient further has type 2 diabetes. 8. The use of any one of claims 1-7, wherein the ophthalmically acceptable carrier comprises an ophthalmically acceptable preservative, an ophthalmically acceptable surfactant, an ophthalmically acceptable viscosity enhancer, an ophthalmically acceptable penetration enhancer, an ophthalmically acceptable gelling agent, an ophthalmically acceptable hydrophobic base, an ophthalmically acceptable buffer, sodium chloride, water, or any combination thereof. 9. The use of any one of claims 1-8, wherein the tolbutamide or pharmaceutically acceptable salt or solvate thereof is for administration in an amount between about 10 μg and about 20 mg. 10. The use of any one of claims 1-9, wherein the tolbutamide or pharmaceutically acceptable salt or solvate thereof is at a concentration of 0.1 - 0.4% (w/v) in said composition. 11. The use of any one of claims 1-10, wherein the composition is for administration from 1 to 4 times per day. 12. The use of any one of claims 1-11, wherein the composition is for ocular administration by topical application to the eye. 13. The use of any one of claims 1-11, wherein the composition is for ocular administration by injection into the anterior chamber of the eye. 14. The use of any one of claims 1-11, wherein the composition is for ocular administration using an ocular insert. 15. The use of any one of claims 1-14, wherein the increase in aqueous humor outflow results in lower intraocular pressure in high tension open angle glaucoma. 16. The use of any one of claims 1-14, wherein the glaucoma is normal tension open angle glaucoma. 17. The use of any one of claims 1-14, wherein the glaucoma is exfoliative angle glaucoma. 18. The use of any one of claims 1-14, wherein the increase in aqueous humor outflow results in lower intraocular pressure after cataract surgery.

Description

METHODS AND COMPOSITIONS FOR IMPROVING EYE HEALTH FIELD OF THE INVENTION The present disclosure relates to eye care products. BACKGROUND OF THE DISCLOSURE All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any 15 publication specifically or implicitly referenced is prior art. Aqueous humor is a transparent, watery fluid similar to plasma, which is secreted from the ciliary epithelium. It's made up of 99.9% water - the other 0.1% consists of sugars, vitamins, proteins and other nutrients. It fills both the anterior and the posterior chambers of the eye. This fluid nourishes the cornea and the lens, as well as giving the eye its shape. 20 The aqueous humor plays an essential role in the health of the eye. As well as nourishing the cornea and the lens by supplying nutrition such as amino acids and glucose, the aqueous humor maintains intraocular pressure, transports vitamin C in the front segment to act as an anti-oxidant agent, and provides inflation for expansion of the cornea, which in tum protects against dust, wind, pollen grains, and a number of pathogens. Thus, continuous production of 25 aqueous humor is critical in ensuring that the optical physics and health of the eye are properly maintained. Production of aqueous humor in the eye may be affected due to several reasons, such as, for example, glaucoma, cataract, old age, etc. Thus, there remains a need in the art for new compositions improving eye health by regulating the production of aqueous humor. Date Rer;ue/Date Received 2023-04-17 WO 2018/204721 PCT /0S2018/030988 SUMMARY OF THE DISCLOSURE Various embodiments disclosed herein include a method of maintaining and/or improving eye health in a subject, comprising: administering to the eye of the subject a therapeuticaily effective amount of a compound that inhibits the Kir6.2 ATP-sensitive K+ 5 (KATP) channel and a pharmaceutically acceptable can-ier. In one embodiment, disclosed herein is a method of maintaining and/or improving eye health in a subject, comprising: administering to the eye of the subject a therapeutically effective amount of a compound that reestablishes the open/close probability requirements of the Kir6.2 KATP channel to normalize aqueous production/outflow dynamics. In one embodiment, the subject has a 10 nonsense mutation, rs5215, in the KCNl 1 gene which is a loss of function mutation defined as a mutation that results in reduced or abolished protein function. In one embodiment, the subject has a V337I mutation in Kir6.2 protein. In one embodiment, the patient has a nonsense mutation, rs5219, in the KCN 11 gene which is a loss of function mutation defined as a mutation that results in reduced or abolished protein function. In one 15 embodiment, the subject has a E23K mutation in Kir6.2 protein. In one embodiment, the compound increases outflow of aqueous humor. In one embodiment, the compound is a glinide. In one embodiment, the compound is a sulfonylurea. In one embodiment, the compound is tolbutamide or a physiologically equivalent salt or solvate thereof. In one embodiment, the pharmaceutically acceptable can-ier is an ophthalmically acceptable 20 carrier. In one embodiment, the compound is administered in an amount between about 10 μg and about 20 mg. In one embodiment, the compound is in a suspension or solution at a concentration of 0.1-0.9% (w/v). In one embodiment, the dosages are administered from 1 to 4 times per day. In one embodiment, the subject is a mammal. In one embodiment, the subject is a human. In one embodiment, the subject is a glaucoma patient. In one 25 embodiment, the glaucoma is normal tension open angle glaucoma. In one embodiment the glaucoma is high tension glaucoma. In one embodiment, the glaucoma is exfoliative angle glaucoma. In one embodiment, the subject is a cataract patient. In one embodiment, the method is performed after cataract surgery. Various embodiments disclosed herein also include a method of treating glaucoma 30 m a patient, comprising: obtaining a biological sample from the patient; testing the biological sample for presence of a mutation in Kir6.2 protein or KCNJI 1 gene; and provided that the biological sample tests positive for the presence of a mutation in Kir6.2 protein or KCNJI I gene, administering to the patient a therapeutically effective amount of a compound that specifically inhibits the Kir6.2 KA TP channel and a pharmaceutically WO 2018/204721 PCT /0S2018/030988 acceptable carrier. In one embodiment, the mutation is a nonsense mutation, rs5215, in the KCNl 1 gene. In one embodiment, the mutation is a V337I mutation in Kir6.2 pro