Acetylcysteine composition and uses thereof

• US 8,399,445 B2
• Filed: 02/27/2012
• Issued: 03/19/2013
• Est. Priority Date: 08/24/2005
• Status: Active Grant

• Current Assignee: Cumberland Pharmaceuticals Inc.
• Original Assignee: Cumberland Pharmaceuticals Inc.
• Inventors: Pavliv, Leo
• Primary Examiner(s): Fetterolf, Brandon
• Assistant Examiner(s): Stone, Christopher R
• Application Number:
  US13/406,175
• Publication Number:
  US 20120309832A1
• Time in Patent Office: 386 Days
• Field of Search: 514/183
• US Class Current: 514/183
• CPC Class Codes: 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
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: 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
• CPC Class Codes: 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
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: 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
• CPC Class Codes: 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
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B65B 7/00 Closing containers or receptacles after filling

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

1. A method of treating acetaminophen overdose, comprising:

using a stable aqueous pharmaceutical composition comprising 200 mg/ml acetylcysteine or pharmaceutically acceptable salts thereof, wherein the composition is free of chelating agents, wherein said composition is in a suitable form for intravenous injection, wherein the pH of the composition is from 6 to 7.5, 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;

diluting the composition in an aqueous solution; and

administering the diluted composition to a patient in need thereof.

2. The method of claim 1, wherein the aqueous solution comprises at least one of 5% dextrose, 0.45% sodium chloride, and water for injection.

3. The method of claim 1, wherein the diluted composition is administered as a loading dose of 150 mg/kg, followed by a second dose of 50 mg/kg, followed by a third dose of 100 mg/kg.

4. The method of claim 1, wherein the total dose of diluted composition administered is 300 mg/kg.

5. The method of claim 1, wherein the pH of the composition is from 6.0 to less than 7.0.

6. A method of treating acetaminophen overdose, comprising:

using a stable aqueous pharmaceutical composition comprising from 200 mg/ml to 250 mg/ml acetylcysteine or pharmaceutically acceptable salts thereof, wherein the composition is free of chelating agents, wherein said composition is in a suitable form for intravenous injection, wherein the pH of the composition is from 6 to 7.5, 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;

diluting the composition in an aqueous solution; and

administering the diluted composition to a patient in need thereof.

7. The method of claim 6, wherein the aqueous solution comprises at least one of 5% dextrose, 0.45% sodium chloride, and water for injection.

8. The method of claim 6, wherein the diluted composition is administered as a loading dose of 150 mg/kg, followed by a second dose of 50 mg/kg, followed by a third dose of 100 mg/kg.

9. The method of claim 6, wherein the total dose of diluted composition administered is 300 ma/ka.

10. A method of treating acetaminophen overdose-induced liver damage, comprising:

using a stable aqueous pharmaceutical composition comprising 200 mg/ml acetylcysteine or pharmaceutically acceptable salts thereof, wherein the composition is free of chelating agents, wherein said composition is in a suitable form for intravenous injection, wherein the pH of the composition is from 6 to 7.5, 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;

diluting the composition in an aqueous solution; and

administering the diluted composition to a patient in need thereof.

11. The method of claim 10, wherein the pH of the composition is from 6.0 to less than 7.0.

12. The method of claim 10, wherein the aqueous solution comprises at least one of 5% dextrose, 0.45% sodium chloride, and water for injection.

13. The method of claim 10, wherein the diluted composition is administered as a loading dose of 150 mg/kg, followed by a second dose of 50 mg/kg, followed by a third dose of 100 mg/kg.

14. The method of claim 10, wherein the total dose of diluted composition administered is 300 mg/kg.

15. The method of claim 10, wherein the patient is in liver failure.

16. The method of claim 15, wherein the liver failure is acute liver failure.