# US 12,214,010 B2 · Desmopressin oral compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,214,010 B2 - Document ID: US12214010B2 - Status: Granted - Kind: B2 - Application number: 18/625,923 - Filed: 2024-04-03 - Published: 2024-10-10 - Granted: 2025-02-04 - Earliest claimed: 2023-04-04 - Assignees: Tulex Pharmaceuticals Inc. - Applicants: Tulex Pharmaceuticals Inc. - Inventors: Yu-Hsing Tu; Kalyan Kathala; Romona Bhattacharya; Yingjun Fan; Ashok Perumal - Web page: https://patentgrep.com/patent/US12214010B2 ## CPC - A61K 38/095: Oxytocins; Vasopressins; Related peptides - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters - A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame} - C07K 7/16: Oxytocins; Vasopressins; Related peptides - 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) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Provided herein are desmopressin oral liquid formulations. Also provided herein are methods of making and using desmopressin oral liquid compositions for the treatment of certain diseases including diabetes insipidus, enuresis, hemophilia A, von willebrand disease, high blood urea levels and others. ## Claims ### Claim 1 A liquid pharmaceutical composition comprising a) desmopressin acetate, wherein desmopressin acetate is present in an amount of from about 0.01 mg/mL to about 0.1 mg/mL; b) a two-component, dual-functional, preservative-buffer system that comprises sodium benzoate and benzoic acid, wherein the two-component, dual-functional, preservative-buffer system provides a pH of the liquid pharmaceutical composition that is about 5.0; and c) water; wherein the liquid pharmaceutical composition is an oral solution. ### Claim 2 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein desmopressin acetate is present in an amount from of about 0.03 mg/mL to about 0.07 mg/mL. ### Claim 3 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein desmopressin acetate is present in an amount of about 0.05 mg/mL. ### Claim 4 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein benzoic acid is present in an amount of from about 0.005% w/v to about 0.1% w/v. ### Claim 5 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein benzoic acid is present in an amount of from about 0.02% w/v to about 0.05% w/v. ### Claim 6 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein sodium benzoate is present in an amount of from about 0.01% w/v to about 0.6% w/v. ### Claim 7 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein sodium benzoate is present in an amount of from about 0.15% w/v to about 0.32% w/v. ### Claim 8 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein benzoic acid and sodium benzoate are present in an amount of from about 0.25% w/v to about 0.35% w/v. ### Claim 9 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein the liquid pharmaceutical composition further comprises a preservative, and wherein the preservative comprises an antimicrobial agent, a chelating agent, an antioxidant, or a combination thereof. ### Claim 10 (depends on 9) The liquid pharmaceutical composition of claim 9, wherein the preservative comprises a paraben or mixture of parabens. ### Claim 11 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein the liquid pharmaceutical composition has a pH that is about 5.0 after stored at 40° C.±2° C. and 75±5% RH for at least 6 months. ### Claim 12 (depends on 1) The liquid pharmaceutical composition of claim 1, comprising: a) desmopressin acetate in an amount of from about 0.01 mg/mL to about 0.1 mg/mL; b) sodium benzoate in an amount of from about 0.18% w/v to about 0.4% w/v; c) benzoic acid in an amount of from about 0.02% w/v to about 0.1% w/v; and d) water. ### Claim 13 (depends on 1) The liquid pharmaceutical composition of claim 1, comprising: a) desmopressin acetate in an amount of from about 0.025 mg/mL to about 0.075 mg/mL; b) sodium benzoate in an amount of from about 0.2% w/v to about 0.35% w/v; c) benzoic acid in an amount of from about 0.03% w/v to about 0.04% w/v; and d) water. ### Claim 14 (depends on 1) The liquid pharmaceutical composition of claim 1, comprising: a) desmopressin acetate in an amount of about 0.05 mg/mL; b) sodium benzoate in an amount of about 0.285% w/v; c) benzoic acid in an amount of about 0.034% w/v; and d) water. ### Claim 15 (depends on 1) The liquid pharmaceutical composition of claim 1, consisting essentially of: a) desmopressin acetate in an amount of about 0.05 mg/ml; b) sodium benzoate in an amount of about 0.285% w/v; c) benzoic acid in an amount of about 0.034% w/v; and d) water. ### Claim 16 (depends on 1) The liquid pharmaceutical composition of claim 1, consisting of a) desmopressin acetate in an amount of about 0.05 mg/mL; b) sodium benzoate in an amount of about 0.285% w/v; c) benzoic acid in an amount of about 0.034% w/v; and d) water. ### Claim 17 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein the liquid pharmaceutical composition is ready-to-use without dilution or addition of any further components to the liquid pharmaceutical composition. ### Claim 18 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein the liquid pharmaceutical composition contains no more than 5% wt of total impurities and not more than 1% wt of each of the following impurities: [Asp5] desmopressin, [Glu4] desmopressin, [Gly′OH] desmopressin, [L-Arg8] desmopressin, [Gln4 (Acm)] desmopressin, [Asn5 (Acm)] desmopressin, and [Gly9N (CH3)2] desmopressin after stored at 40° C.±2° C. and 75±5% RH humidity for 6 months, wherein the amount of impurities is determined according to High-performance liquid chromatography (HPLC) method. ### Claim 19 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein the liquid pharmaceutical composition retains at least 90% wt of the initial desmopressin acetate amount after stored at 40° C.±2° C. and 75±5% RH for 6 months, wherein the desmopressin acetate amount is determined according to High-performance liquid chromatography (HPLC) method. ### Claim 20 (depends on 1) The liquid pharmaceutical composition of claim 1, wherein the liquid pharmaceutical composition exhibits a bioavailability that is bioequivalent to a reference oral tablet composition comprising desmopressin acetate, when measured as the total area under the curve (AUC) after oral administration or when measured as Cmax after oral administration. ### Claim 21 (depends on 1) A direct dosing device comprising the liquid pharmaceutical composition of claim 1. ### Claim 22 (depends on 1) A kit comprising a package enclosing the liquid pharmaceutical composition of claim 1.