# US 12,599,556 B2 · Ophthalmic compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,599,556 B2 - Document ID: US12599556B2 - Status: Granted - Kind: B2 - Application number: 18/264,938 - Filed: 2022-02-10 - Published: 2024-10-03 - Granted: 2026-04-14 - Earliest claimed: 2021-02-11 - Assignees: Biotheravision Inc. - Applicants: Biotheravision, Inc. - Inventors: Roland Bodmeier; Chin-Ming Chang - Web page: https://patentgrep.com/patent/US12599556B2 ## CPC - A61K 9/10: Dispersions; Emulsions - A61K 9/0048: {Eye, e.g. artificial tears} - A61K 31/407: condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine - A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - A61K 47/186: {Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide} - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61K 47/38: Cellulose; Derivatives thereof - A61K 47/40: Cyclodextrins; Derivatives thereof - A61P 27/00: Drugs for disorders of the senses - 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 invention provides an aqueous liquid composition for ophthalmic administration, comprising therapeutically effective amounts of a ketorolac compound and of a corticosteroid, wherein the ketorolac compound is present in an essentially dissolved form; wherein the corticosteroid is present in the form of suspended particles; and wherein the composition exhibits an acidic pH of about 6.5 or less. The invention further provides compositions as disclosed herein for use in the prevention or treatment of ocular inflammation and methods for preventing or treating ocular inflammation in a subject. ## Claims ### Claim 1 An aqueous liquid composition for ophthalmic administration, comprising therapeutically effective amounts of a ketorolac compound and of a corticosteroid, wherein the ketorolac compound is present in an essentially dissolved form; wherein the corticosteroid is present in the form of suspended particles; wherein the composition exhibits an acidic pH of about 6.5 or less; and wherein the viscosity of the aqueous liquid composition is in the range from about 1 to about 60 centipoise (cps) or millipascal-second (mPa·s). ### Claim 2 (depends on 1) The composition of claim 1, wherein the corticosteroid is selected from dexamethasone, prednisolone, fluorometholone, betamethasone, difluprednate, triamcinolone, remexolone, loteprednol, and clobetasol, or any salt, ester, acetonide or other hydrolysable prodrug thereof. ### Claim 3 (depends on 1) The composition of claim 1, being essentially free of a buffer system. ### Claim 4 (depends on 1) The composition of claim 1, being essentially free of sodium chloride. ### Claim 5 (depends on 1) The composition of claim 1, having a pH of about 5-6. ### Claim 6 (depends on 1) The composition of claim 1, further characterised in that it exhibits a surface tension in the range from about 20 to 70 dyne per centimeter (dyn/cm) or about 0.020 to 0.070 newton per meter (N/m), and/or a zeta potential in the range from about +/−10 to +/−40 millivolt (mV). ### Claim 7 (depends on 1) The composition of claim 1, wherein the ketorolac compound is ketorolac tromethamine. ### Claim 8 (depends on 1) The composition of claim 1, wherein the corticosteroid is a loteprednol compound. ### Claim 9 (depends on 1) The composition of claim 1, further comprising: (a) a polymeric viscosity-enhancing agent; (b) a non-ionic surfactant; and/or (c) a low-molecular weight polyol; wherein the low-molecular weight polyol refers to an organic compound comprising more than one hydroxyl (—OH) group and having a molecular weight from about 45 g/mol to about 450 g/mol. ### Claim 10 (depends on 9) The composition of claim 9, wherein the polymeric viscosity-enhancing agent is a non-ionic, water-soluble polymer. ### Claim 11 (depends on 10) The composition of claim 10, wherein the polymeric viscosity-enhancing agent is polyvinylpyrrolidone. ### Claim 12 (depends on 9) The composition of claim 9, wherein the non-ionic surfactant is tyloxapol; and wherein the concentration of tyloxapol in the composition is from about 0.1 wt. % to about 1.2 wt. %. ### Claim 13 (depends on 9) The composition of claim 9, wherein the low-molecular weight polyol is glycerol; and wherein the concentration of glycerol in the composition is from about 0.5 wt. % to about 2.5 wt. %. ### Claim 14 (depends on 9) The composition of claim 9, comprising a further polymeric viscosity-enhancing agent, said further polymeric viscosity-enhancing agent being selected from anionic carbohydrates including any salts thereof. ### Claim 15 (depends on 1) The composition of claim 1, being essentially free of poloxamer. ### Claim 16 (depends on 7) The composition of claim 7, further comprising a cyclodextrin. ### Claim 17 (depends on 1) The composition of claim 1, further comprising ethylenediaminetetraacetic acid (EDTA). ### Claim 18 (depends on 17) The composition of claim 17, wherein the composition consists essentially of (a) a ketorolac tromethamine; (b) a corticosteroid; (c) a tyloxapol; (d) a polyvinylpyrrolidone; (e) a sodium carboxymethyl cellulose; (f) a glycerol; (g) EDTA; (h) a benzalkonium chloride; (i) a water; and optionally (k) a 2-hydroxypropyl-β-cyclodextrin and/or an acid or base to adjust the pH, wherein the pH of the composition is about 5-6. ### Claim 19 (depends on 1) The composition of claim 1, wherein the suspended particles have a D90 of about less than 20 μm. ### Claim 20 (depends on 1) The composition of claim 1, being essentially free of a cross-linked, carboxy containing polymer. ### Claim 21 (depends on 1) The composition of claim 1, being essentially free of chitosan. ### Claim 22 (depends on 1) A method for preventing or treating ocular inflammation in a subject, said method comprising topically administering the composition of claim 1 to an eye of said subject.