# US 12,005,142 B2 · Sustained-release compositions comprising a therapeutic agent for treating depression or anxiety and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,142 B2 - Document ID: US12005142B2 - Status: Granted - Kind: B2 - Application number: 17/264,552 - Filed: 2019-07-31 - Published: 2021-10-07 - Granted: 2024-06-11 - Earliest claimed: 2018-08-02 - Applicants: Taiwan Liposome Co., Ltd.; Tlc Biopharmaceuticals, Inc. - Inventors: Keelung Hong; Yi-Yu Lin; Hao-Wen Kao - Web page: https://patentgrep.com/patent/US12005142B2 ## CPC - A61K 9/1273: Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances - A61K 31/46: 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) - A61K 47/02: Inorganic compounds - A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids - 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 - A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid - A61P 25/22: Anxiolytics - A61P 25/24: Antidepressants - A61K 9/1278: Post-loading, e.g. by ion or pH gradient - 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 relates to a pharmaceutical composition comprising at least one liposome and a therapeutic agent for treating depression or anxiety, with a therapeutic agent to lipid ratio equal to or higher than about 0.15. The pharmaceutical composition improves the pharmacokinetic profile and sustains the release of the therapeutic agent. Also provided is the method for treating depression or anxiety using the pharmaceutical composition disclosed herein. ## Claims ### Claim 1 A pharmaceutical composition, comprising (a) at least one liposome comprising a bilayer membrane, said bilayer membrane comprises a first lipid that is HSPC, DMPC or any combination thereof, cholesterol and a second lipid that is PEG-DSPE; (b) a trapping agent that is triethylammonium sucrose octasulfate, ammonium sulfate, or any combination thereof; and (c) a therapeutic agent that is ketamine, wherein the molar ratio of the therapeutic agent to the lipid is equal to or higher than about 0.2, the therapeutic agent is encapsulated in the liposomes with an encapsulation efficiency higher than about 60% and the mean particle size of the liposome is from about 50 nm to about 20 μm. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the mole % of first lipid: second lipid: cholesterol is 40-70%: 0.1-25%: 25-45%. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the concentration of triethylammonium sucrose octasulfate is about 10 to 200 mM. ### Claim 4 (depends on 1) The pharmaceutical composition of claim 1, wherein the concentration of ammonium sulfate is about 100 to 600 mM. ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the bilayer membrane comprises a first lipid that is HSPC, cholesterol and a second lipid that is PEG-DSPE, with an encapsulation efficiency higher than about 75%. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein said ketamine is selected from the group consisting essentially of (R,S)-ketamine, (R)-ketamine and (S)-ketamine. ### Claim 7 (depends on 1) The pharmaceutical composition of claim 1, further comprising a pharmaceutically acceptable excipient, a diluent, a medium for an active ingredient, a preservative, a cryoprotectant or a combination thereof. ### Claim 8 (depends on 1) A method of treating depression or anxiety, comprising: administering the pharmaceutical composition of claim 1 to a subject in need thereof. ### Claim 9 (depends on 8) The method of claim 8, wherein the half-life of the therapeutic agent in the pharmaceutical composition is extended by at least 2-fold compared to that of a free therapeutic agent. ### Claim 10 (depends on 8) The method of claim 8, wherein the pharmaceutical composition is administered at least once every three days, at least once every week, at least once every two weeks or at least once a month. ### Claim 11 (depends on 8) The method of claim 8, wherein the pharmaceutical composition is administered by cutaneous injection. ### Claim 12 (depends on 11) The method of claim 11, wherein the cutaneous injection includes subcutaneous, subdermal, intradermal or intramuscular route. ### Claim 13 A pharmaceutical composition, comprising (a) at least one liposome comprising a bilayer membrane, said bilayer membrane comprises a first lipid that is HSPC, DPPC or any combination thereof, cholesterol and optionally a second lipid that is PEG-DSPE, DPPG or any combination thereof; (b) a trapping agent that is 10 to 200 mM triethylammonium sucrose octasulfate, 300 to 600 mM ammonium sulfate, 100 to 600 mM ammonium phosphate or any combination thereof; and (c) a therapeutic agent that is scopolamine, wherein the molar ratio of the therapeutic agent to the lipid is equal to or higher than about 0.15, the therapeutic agent is encapsulated in the liposomes with an encapsulation efficiency higher than about 60% and the mean particle size of the liposome is from about 50 nm to about 20 μm. ### Claim 14 (depends on 13) The pharmaceutical composition of claim 13, wherein the mole % of first lipid: second lipid: cholesterol is 40-70%: 0.1-25%: 25-45%. ### Claim 15 (depends on 13) The pharmaceutical composition of claim 13, wherein the trapping agent is 10 to 200 mM triethylammonium sucrose octasulfate, 300 to 600 mM ammonium sulfate, or any combination thereof; the molar ratio of the therapeutic agent to the lipid is equal to or higher than about 0.15, the therapeutic agent is encapsulated in the liposomes with an encapsulation efficiency higher than about 65%. ### Claim 16 (depends on 13) The pharmaceutical composition of claim 13, further comprising a pharmaceutically acceptable excipient, a diluent, a medium for an active ingredient, a preservative, a cryoprotectant or a combination thereof. ### Claim 17 (depends on 13) A method of treating depression or anxiety, comprising: administering the pharmaceutical composition of claim 13 to a subject in need thereof. ### Claim 18 (depends on 17) The method of claim 17, wherein the half-life of the therapeutic agent in the pharmaceutical composition is extended by at least 2-fold compared to that of a free therapeutic agent. ### Claim 19 (depends on 17) The method of claim 17, wherein the pharmaceutical composition is administered at least once every three days, at least once every week, at least once every two weeks or at least once a month. ### Claim 20 (depends on 17) The method of claim 17, wherein the pharmaceutical composition is administered by cutaneous injection.