# US 8,148,356 B2 · Acetylcysteine composition and uses therefor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,148,356 B2 - Document ID: US8148356B2 - Status: Granted - Kind: B2 - Application number: 11/209,804 - Filed: 2005-08-24 - Published: 2007-03-01 - Granted: 2012-04-03 - Earliest claimed: 2005-08-24 - Assignees: Cumberland Pharmaceuticals Inc. - Inventors: Leo Pavliv - Web page: https://patentgrep.com/patent/US8148356B2 ## CPC - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61J 1/05: for collecting, storing or administering blood, plasma or medical fluids {(multiple bags systems for separating or storing blood components A61M1/0209); Infusion or perfusion containers} - 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 31/195: having an amino group - A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205) - A61K 47/02: Inorganic compounds - 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 - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 13/12: of the kidneys - A61P 25/30: for treating abuse or dependence - A61P 35/00: Antineoplastic agents - A61P 39/02: Antidotes - A61P 39/06: Free radical scavengers or antioxidants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - B65B 7/00: Closing containers or receptacles after filling - 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) - A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - B65B: MACHINES, APPARATUS OR DEVICES FOR, OR METHODS OF, PACKAGING ARTICLES OR MATERIALS; UNPACKING (bundling and pressing devices for cigars A24C1/44; devices for tensioning and securing binders adapted to be supported by the article or articles to be bound B25B25/00; applying closure members to bottles, jars or similar containers B67B1/00-B67B6/00; concurrent cleaning, filling and closing of bottles B67C7/00; emptying bottles, jars, cans, casks, barrels or similar containers B67C9/00) ## Abstract This invention relates to novel acetylcysteine compositions in solution, comprising acetylcysteine and which are substantially free of metal chelating agents, such as EDTA. Further, this invention relates to methods of making and using the acetylcysteine compositions. The present compositions and methods are designed to improve patient tolerance and compliance, while at the same time maintaining the stability of the pharmaceutical formulation. The compositions and methods of this invention are useful in the treatment of acetaminophen overdose, acute liver failure, various cancers, methacrylonitrile poisoning, reperfusion injury during cardio bypass surgery, and radiocontrast-induced nephropathy, and can also be used as a mucolytic agent. ## Claims ### Claim 1 A stable aqueous pharmaceutical composition comprising between 200 and 250 mg/mL acetylcysteine, wherein the composition is free from a chelating agent, or pharmaceutically acceptable salts thereof, wherein said composition is in a suitable form for intravenous injection, wherein the pH of the composition is from 6 to 7, and wherein said composition is sealed in an airtight container comprising a fill volume of said composition and a headspace volume occupied by a pharmaceutically inert gas. ### Claim 2 (depends on 1) The aqueous pharmaceutical composition of claim 1, wherein the composition contains no EDTA, or pharmaceutically acceptable salts thereof. ### Claim 3 (depends on 1) The aqueous pharmaceutical composition of claim 1, wherein the pH of the composition is from 6.5 to less than 7.0. ### Claim 4 (depends on 3) The aqueous pharmaceutical composition of claim 3, wherein the pH of the composition is 6.8. ### Claim 5 (depends on 1) The aqueous pharmaceutical composition of claim 1, wherein the composition is stable for at least 12 months at 25° C. ### Claim 6 (depends on 1) The aqueous pharmaceutical composition of claim 1, wherein the composition is stable for at least 6 months at 40° C. ### Claim 7 An aqueous pharmaceutical composition consisting of between 200 and 250 mg/mL acetylcysteine, or pharmaceutically acceptable salts thereof dissolved in deaerated water, and wherein the pH of the composition is adjusted with a pH-adjusting agent to a pH of from 6 to less than 7, wherein said composition is in a suitable form for intravenous injection and is free of a chelating agent, and wherein said composition is sealed in an airtight container comprising a fill volume of said composition and a headspace volume occupied by a pharmaceutically inert gas. ### Claim 8 An aqueous pharmaceutical composition consisting of between 200 and 500 mg/mL acetylcysteine, or pharmaceutically acceptable salts thereof, dissolved in deaerated water, and wherein the pH of the composition is adjusted with a pH-adjusting agent to a pH of from 6 to less than 7, wherein said composition is in a suitable form for intravenous injection and is free of a chelating agent, and wherein said composition is sealed in an airtight container comprising a fill volume of said composition and a headspace volume occupied by a pharmaceutically inert gas. ### Claim 9 A container comprising: an aqueous pharmaceutical composition comprising between 200 and 500 mg/mL acetylcysteine, wherein the composition is free of a chelating agent and has a pH of about 6 to less than 7, or pharmaceutically acceptable salts thereof, and wherein said composition is in a suitable form for intravenous injection; and a headspace consisting essentially of a pharmaceutically inert gas. ### Claim 10 (depends on 9) The container of claim 9, wherein the pharmaceutically inert gas is nitrogen. ### Claim 11 (depends on 1) The composition of claim 1, wherein the composition has a substantially constant acetylcysteine amount through at least 3 months of storage. ### Claim 12 (depends on 1) The composition of claim 1, wherein the composition has a substantially constant acetylcysteine amount through at least 12 months of storage. ### Claim 13 (depends on 1) The composition of claim 1, wherein the acetylcysteine amount through at least 12 months of storage is at least 99% of the original amount. ### Claim 14 (depends on 9) The composition of claim 9, wherein the chelating agent is EDTA.