# US 9,750,721 B2 · Therapeutic agent for keratoconjunctive disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,750,721 B2 - Document ID: US9750721B2 - Status: Granted - Kind: B2 - Application number: 15/293,548 - Filed: 2016-10-14 - Published: 2017-03-09 - Granted: 2017-09-05 - Earliest claimed: 2012-11-08 - Assignees: Yamaguchi University - Applicants: Yamaguchi University - Inventors: Kazuhiro Kimura - Web page: https://patentgrep.com/patent/US9750721B2 ## CPC - A61K 31/415: 1,2-Diazoles - A61K 9/0048: {Eye, e.g. artificial tears} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)} - A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 27/02: Ophthalmic agents - A61P 27/04: Artificial tears; Irrigation solutions - A61P 27/14: Decongestants or antiallergics - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention addresses the problem of providing a novel therapeutic agent for keratoconjunctive disorders. As a means for solving the problem, a therapeutic agent for keratoconjunctive disorders which contains a RARγ agonist as an active ingredient is provided. The therapeutic agent exhibits an excellent ameliorating effect in a keratoconjunctive disorder model, and is therefore useful as a therapeutic agent for keratoconjunctive disorders such as corneal ulcer, corneal epithelial abrasion, keratitis, dry eye, conjunctivitis, chronic superficial keratitis, corneal erosion, persistent corneal disorders, superficial punctate keratopathy, corneal epithelial defects, conjunctival epithelial defects, keratoconjunctivitis sicca, superior limbic keratoconjunctivitis, filamentary keratoconjunctivitis, infectious keratitis, noninfectious keratitis, infectious conjunctivitis and noninfectious conjunctivitis. The therapeutic agent is also useful as a therapeutic agent for corneal scarring and conjunctival scarring both associated with keratoconjunctive disorders. ## Claims ### Claim 1 A method of preventing or treating dry eye or scar formation in the eye of a subject in need thereof, comprising administering to the subject (E)-4-(2-{3-[(1H-pyrazole-1-yl)methyl]-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-yl}vinyl)benzoic acid (R667), or an ester or salt thereof, in an amount effective to prevent or treat the dry eye or scar formation. ### Claim 2 (depends on 1) The method of claim 1, wherein the method comprises preventing or treating dry eye in the subject. ### Claim 3 (depends on 1) The method of claim 1, wherein the method comprises preventing or treating scar formation in the eye of the subject. ### Claim 4 (depends on 3) The method of claim 3, wherein the method prevents or reduces scar formation on the conjunctiva and/or cornea of the subject. ### Claim 5 (depends on 1) The method of claim 1, wherein the R667, or a salt thereof, is in the form of a powder, syrup, granule, liquid formulation, suspension, emulsion, ointment, or instillation. ### Claim 6 (depends on 5) The method of claim 5, wherein the ointment is an ophthalmic ointment. ### Claim 7 (depends on 6) The method of claim 6, wherein the ointment comprises a solubilizer. ### Claim 8 (depends on 7) The method of claim 7, wherein the solubilizer is selected from the group consisting of polysorbate 80, polyoxylethylene hydrogenated castor oil 60, and macrogol 4000. ### Claim 9 (depends on 8) The method of claim 8, wherein the solubilizer is polysorbate 80. ### Claim 10 (depends on 6) The method of claim 6, wherein the concentration of the R667, or a salt thereof, in the ophthalmic ointment administered to the subject is from 0.0001% to 3% (w/v). ### Claim 11 (depends on 10) The method of claim 10, wherein the concentration of the R667, or a salt thereof, in the ophthalmic ointment administered to the subject is from 0.001% to 1% (w/v). ### Claim 12 (depends on 5) The method of claim 5, wherein the R667, or a salt thereof, is in the form of an instillation. ### Claim 13 (depends on 12) The method of claim 12, wherein the instillation comprises a solubilizer. ### Claim 14 (depends on 13) The method of claim 13, wherein the solubilizer is selected from the group consisting of polysorbate 80, polyoxylethylene hydrogenated castor oil 60, and macrogol 4000. ### Claim 15 (depends on 14) The method of claim 14, wherein the solubilizer is polysorbate 80. ### Claim 16 (depends on 12) The method of claim 12, wherein the concentration of the R667, or a salt thereof, in the instillation administered to the subject is from 0.00001% to 3% (w/v). ### Claim 17 (depends on 16) The method of claim 16, wherein the concentration of the R667, or a salt thereof, in the instillation administered to the subject is from 0.0001% to 1% (w/v). ### Claim 18 (depends on 17) The method of claim 17, wherein the concentration of the R667, or a salt thereof, in the instillation administered to the subject is 0.3% (w/v), 0.5% (W/V), or 1% (W/V). ### Claim 19 (depends on 1) The method of claim 1, wherein the administering is administering by instillation. ### Claim 20 (depends on 1) The method of claim 1, wherein the R667, or a salt thereof, is administered to the subject in one or more daily doses.