# US 11,433,044 B2 · Pharmaceutical formulations for subcutaneous administration of furosemide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,433,044 B2 - Document ID: US11433044B2 - Status: Granted - Kind: B2 - Application number: 16/295,085 - Filed: 2019-03-07 - Published: 2020-02-06 - Granted: 2022-09-06 - Earliest claimed: 2013-04-05 - Assignees: scPharmaceuticals Inc. - Applicants: scPharmaceuticals Inc. - Inventors: Scott A. Michaels; Pieter Muntendam; Glenn R. Larsen - Web page: https://patentgrep.com/patent/US11433044B2 ## CPC - A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine - 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 9/08: Solutions {(composition of solutions A61K47/00)} - A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine - A61K 47/02: Inorganic compounds - A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids - A61P 7/10: Antioedematous agents; Diuretics - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 9/12: Antihypertensives - 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 teachings relate to liquid pharmaceutical formulations of furosemide, where the pharmaceutical formulations include a molar excess of tris(hydroxymethyl)aminomethane to furosemide, have a pH in the range of 7 to 8.5, and a concentration of tris(hydroxymethyl)aminomethane greater than or equal to about 50 mM. The present teachings can improve the stability of liquid pharmaceutical formulations including furosemide and the suitability of such pharmaceutical formulations for subcutaneous administration or delivery. ## Claims ### Claim 1 A method of treating a human with or exhibiting the symptoms of edema, hypertension or heart failure, the method comprising: administering subcutaneously to a human a liquid pharmaceutical formulation, wherein the liquid pharmaceutical formulation comprises: furosemide as the sole therapeutically active agent in the liquid pharmaceutical formulation, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 5 mg/mL or greater; and tris(hydroxymethyl)aminomethane, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 500 mM; wherein the liquid pharmaceutical formulation is isosmotic and has a pH between about 7 to about 8.5, and the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than about 1.5. ### Claim 2 (depends on 1) The method of claim 1, wherein the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than or equal to two. ### Claim 3 (depends on 1) The method of claim 1, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 250 mM. ### Claim 4 (depends on 1) The method of claim 1, wherein the liquid pharmaceutical formulation has a pH between about 7.2 to about 8. ### Claim 5 (depends on 1) The method of claim 1, wherein the amount of furosemide in the liquid_pharmaceutical formulation is between about 6 mg/mL to about 15 mg/mL. ### Claim 6 (depends on 1) The method of claim 1, wherein administering subcutaneously comprises using a pump device. ### Claim 7 (depends on 6) The method of claim 6, wherein the pump device is a patch device. ### Claim 8 A method of treating a human with or exhibiting the symptoms of edema, hypertension or heart failure, the method comprising: administering subcutaneously to a human using a patch device a liquid pharmaceutical formulation comprising: furosemide as the sole therapeutically active agent in the liquid pharmaceutical formulation, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 15 mg/mL or greater; and tris(hydroxymethyl)aminomethane, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 500 mM; wherein the liquid pharmaceutical formulation is isosmotic and has a pH between about 7.2 to about 8, and the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than or equal to 1.5. ### Claim 9 (depends on 1) The method of claim 1, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 150 mM. ### Claim 10 (depends on 1) The method of claim 1, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 100 mM. ### Claim 11 (depends on 1) The method of claim 1, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 15 mg/mL or greater. ### Claim 12 (depends on 1) The method of claim 1, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 20 mg/mL or greater. ### Claim 13 (depends on 1) The method of claim 1, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 25 mg/mL or greater. ### Claim 14 (depends on 8) The method of claim 8, wherein the molar ratio of tris(hydroxymethyl)aminomethane to furosemide is greater than or equal to two. ### Claim 15 (depends on 8) The method of claim 8, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 250 mM. ### Claim 16 (depends on 8) The method of claim 8, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 150 mM. ### Claim 17 (depends on 8) The method of claim 8, wherein the concentration of tris(hydroxymethyl)aminomethane in the liquid pharmaceutical formulation is in a range of about 50 mM to about 100 mM. ### Claim 18 (depends on 8) The method of claim 8, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 15 mg/mL or greater. ### Claim 19 (depends on 8) The method of claim 8, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 20 mg/mL or greater. ### Claim 20 (depends on 8) The method of claim 8, wherein the amount of furosemide in the liquid pharmaceutical formulation is about 25 mg/mL or greater.