# US 11,304,924 B2 · Pharmaceutical compositions comprising nitroxyl donors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,304,924 B2 - Document ID: US11304924B2 - Status: Granted - Kind: B2 - Application number: 16/779,015 - Filed: 2020-01-31 - Published: 2020-05-28 - Granted: 2022-04-19 - Earliest claimed: 2013-01-18 - Assignees: Cardioxyl Pharmaceuticals, Inc. - Applicants: Cardioxyl Pharmaceuticals, Inc. - Inventors: Vincent Jacob Kalish; John Reardon; Frederick Arthur Brookfield; Stephen Martin Courtney; Lisa Marie Frost; John P. Toscano - Web page: https://patentgrep.com/patent/US11304924B2 ## 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 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63) - A61K 31/222: with compounds having aromatic groups, e.g. dipivefrine, ibopamine - A61K 31/24: having an amino or nitro group - A61K 31/255: of sulfoxy acids or sulfur analogues thereof - A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone - A61K 31/381: having five-membered rings - A61K 31/404: Indoles, e.g. pindolol - A61K 31/42: Oxazoles - A61K 31/433: Thidiazoles - A61K 31/4436: containing a heterocyclic ring having sulfur as a ring hetero atom - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 31/538: ortho- or peri-condensed with carbocyclic ring systems - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/40: Cyclodextrins; Derivatives thereof - A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - C07C 317/14: having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings - C07D 307/64: Sulfur atoms - 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 - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The present disclosure provides nitroxyl donating pharmaceutical compositions comprising N-substituted hydroxylamine derivatives. The compositions are highly efficacious in treating cardiovascular diseases (e.g., heart failure), have a suitable toxicological profile, and are sufficiently stable for intravenous or oral administration. ## Claims ### Claim 1 A method of treating heart failure, comprising intravenously administering to a human patient a nitroxyl donor composition comprising a compound of the formula (1): wherein said composition is administered at a pH of from about 5 to about 6.5 and at a dose of about 1 μg/kg/min to about 30 μg/kg/min. ### Claim 2 (depends on 1) The method of claim 1, wherein the composition is administered at a pH of from about 5.5 to about 6. ### Claim 3 (depends on 1) The method of claim 1, wherein the composition is administered at a pH of about 6. ### Claim 4 (depends on 1) The method of claim 1, wherein the composition further comprises a stabilizing agent. ### Claim 5 (depends on 4) The method of claim 4, wherein the stabilizing agent is a cyclodextrin. ### Claim 6 (depends on 5) The method of claim 5, wherein the cyclodextrin is a β-cyclodextrin. ### Claim 7 A method of treating acute decompensated heart failure, comprising intravenously administering to a human patient a nitroxyl donor composition comprising a compound of the formula (1): wherein said composition is administered at a pH of from about 5 to about 6.5 and at a dose of about 1 μg/kg/min to about 30 μg/kg/min. ### Claim 8 (depends on 7) The method of claim 7, wherein the composition is administered at a pH of from about 5.5 to about 6. ### Claim 9 (depends on 7) The method of claim 7, wherein the composition is administered at a pH of about 6. ### Claim 10 (depends on 7) The method of claim 7, wherein the composition further comprises a stabilizing agent. ### Claim 11 (depends on 10) The method of claim 10, wherein the stabilizing agent is a cyclodextrin. ### Claim 12 (depends on 11) The method of claim 11, wherein the cyclodextrin is a β-cyclodextrin. ### Claim 13 (depends on 1) The method of claim 1, wherein the composition is administered at a dose of at least 2.5 μg/kg/min. ### Claim 14 (depends on 1) The method of claim 1, wherein the composition is administered in an amount of at least 5 μg/kg/min. ### Claim 15 (depends on 1) The method of claim 1, wherein the composition is administered at a dose of at least 7.5 μg/kg/min. ### Claim 16 (depends on 1) The method of claim 1, wherein the composition is administered at a dose of at least 12 μg/kg/min. ### Claim 17 (depends on 1) The method of claim 1, wherein the composition is administered at a dose of at least 15 μg/kg/min. ### Claim 18 (depends on 7) The method of claim 7, wherein the composition is administered at a dose of at least 2.5 μg/kg/min. ### Claim 19 (depends on 7) The method of claim 7, wherein the composition is administered in an amount of at least 5 μg/kg/min. ### Claim 20 (depends on 7) The method of claim 7, wherein the composition is administered at a dose of at least 7.5 μg/kg/min. ### Claim 21 (depends on 7) The method of claim 7, wherein the composition is administered at a dose of at least 12 μg/kg/min. ### Claim 22 (depends on 7) The method of claim 7, wherein the composition is administered at a dose of at least 15 μg/kg/min.