# US 11,992,561 B2 · Oral thin film of polyvinyl alcohol and polyvinyl alcohol-polyethylene glycol graft copolymer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,992,561 B2 - Document ID: US11992561B2 - Status: Granted - Kind: B2 - Application number: 17/900,616 - Filed: 2022-08-31 - Published: 2023-06-01 - Granted: 2024-05-28 - Earliest claimed: 2020-11-09 - Assignees: LTS Lohmann Therapie-Systeme AG - Applicants: Lts Lohmann Therapie-Systeme AG - Inventors: Markus Müller; Mario Ficker; Michael Linn; Florian Hammes - Web page: https://patentgrep.com/patent/US11992561B2 ## CPC - A61K 9/7007: {Drug-containing films, membranes or sheets (A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence)} - A61K 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays} - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - 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 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - 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 Described is an oral thin film comprising at least one matrix layer, wherein the at least one matrix layer comprises at least one pharmaceutically active agent, at least one polyvinyl alcohol and at least one polyvinyl alcohol-polyethylene glycol graft copolymer, a method for producing same, and use thereof as a medicament. ## Claims ### Claim 1 An oral thin film comprising at least one matrix layer, wherein the at least one matrix layer comprises ketamine in an amount of 45 to 70 wt. %, in relation to the total weight of the matrix layer, at least one polyvinyl alcohol with a mean molecular weight of 200,000 to 210,000 g/mol, in an amount of 5 to 40 wt. % in relation to the total weight of the matrix layer, and at least one polyvinyl alcohol-polyethylene glycol graft copolymer in an amount of 15 to 45 wt. % in relation to the total weight of the matrix layer. ### Claim 2 (depends on 1) The oral thin film according to claim 1, wherein ketamine comprises a pharmaceutic ally acceptable salt of ketamine. ### Claim 3 (depends on 1) The oral thin film according to claim 1, wherein the matrix layer further includes at least one polyvinyl alcohol with a mean molecular weight of approximately 25,000 to approximately 35,000 g/mol. ### Claim 4 (depends on 1) The oral thin film according to claim 1, wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units. ### Claim 5 (depends on 1) The oral thin film according to claim 1, wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units, wherein the molar ratio of polyethylene glycol to polyvinyl alcohol is 1:3. ### Claim 6 (depends on 1) The oral thin film according to claim 1, wherein the at least one polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units, wherein the polyvinyl alcohol-polyethylene glycol graft copolymer has a mean molecular weight in the range of 40,000 to 50,000 g/mol. ### Claim 7 (depends on 1) The oral thin film according to claim 1, wherein the oral thin film further comprises at least one auxiliary substance selected from the group comprising colouring agents, flavourings, sweeteners, plasticisers, taste-masking agents, emulsifiers, enhancers, pH regulators, humectants, preservatives and/or antioxidants. ### Claim 8 (depends on 1) The oral thin film according to claim 1, wherein the area density of the oral thin film is approximately 50 to 300 g/m. ### Claim 9 (depends on 1) The oral thin film according to claim 1, wherein the ketamine comprises ketamine as a free base in a total amount of 25 to 150 mg. ### Claim 10 (depends on 1) The oral thin film according to claim 1, wherein at least 40% of the ketamine is released within the first minute following application, and/or wherein at least 75% of the ketamine is released within the first two minutes following application. ### Claim 11 (depends on 1) The oral thin film according to claim 1, wherein the puncture strength is at least 0.15 N/mm with an areal density of 150 to 250 g/m. ### Claim 12 (depends on 1) The oral thin film according to claim 1, wherein the matrix layer comprises 60 wt. % of (S)-ketamine HCl, 10 wt. % of a polyvinyl alcohol with a mean molecular weight of approximately 200,000 to 210,000 g/mol, and 20.1 wt. % of a polyvinyl alcohol-polyethylene glycol graft copolymer, wherein the polyvinyl alcohol-polyethylene glycol graft copolymer has a polyethylene glycol main chain onto which there are grafted polyvinyl alcohol units, and wherein the polyvinyl alcohol-polyethylene glycol graft copolymer has a mean molecular weight in the range of 40,000 to 50,000 g/mol. ### Claim 13 (depends on 1) The oral thin film according to claim 1, wherein the maximum plasma concentration of (S)-ketamine following administration of a dose of 50 mg (S)-ketamine lies at 50 to 200 ng/mL, or wherein the maximum plasma concentration of (S)-ketamine following administration of a dose of 100 mg (S)-ketamine lies at 100 to 200 ng/mL. ### Claim 14 (depends on 1) The oral thin film according to claim 1, wherein the maximum plasma concentration of the ketamine metabolite (S)-norketamine following administration of a dose of 50 mg (S)-ketamine lies at 200 to 400 ng/mL, or wherein the maximum plasma concentration of the ketamine metabolite (S)-norketamine following administration of a dose of 100 mg (S)-ketamine lies at 300 to 500 ng/mL. ### Claim 15 (depends on 1) The oral thin film according to claim 1, wherein the maximum plasma concentration of the ketamine metabolite (S)-hydroxynorketamine following administration of a dose of 50 mg (S)-ketamine lies at 50 to 150 ng/mL, or wherein the maximum plasma concentration of the ketamine metabolite (S)-hydroxynorketamine following administration of a dose of 100 mg (S)-ketamine lies at 100 to 250 ng/mL.