Acetylcysteine Composition and Uses Thereof

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.

1 . (canceled) 
     
     
         2 . An aqueous pharmaceutical composition comprising acetylcysteine, wherein the composition contains less than 0.05% w/v EDTA, or pharmaceutically acceptable salts thereof. 
     
     
         3 . The aqueous pharmaceutical composition of  claim 2 , wherein the composition contains less than 0.02% w/v EDTA, or pharmaceutically acceptable salts thereof. 
     
     
         4 . The aqueous pharmaceutical composition of  claim 3 , wherein the composition contains no EDTA, or pharmaceutically acceptable salts thereof. 
     
     
         5 . The aqueous pharmaceutical composition of  claim 2 , wherein the pH of the composition is from 6 to 8. 
     
     
         6 . The aqueous pharmaceutical composition of  claim 5 , wherein the pH of the composition is from 6.5 to 7.0. 
     
     
         7 . The aqueous pharmaceutical composition of  claim 6 , wherein the pH of the composition is 6.8. 
     
     
         8 . The aqueous pharmaceutical composition of  claim 2 , wherein the composition is stable for at least 12 months at 25° C. 
     
     
         9 . The aqueous pharmaceutical composition of  claim 2 , wherein the composition is stable for at least 6 months at 40° C. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . A method of treating acetaminophen overdose, comprising administering to a patient in need thereof an effective amount of an aqueous composition of acetylcysteine, wherein said composition contains less than 0.05% w/v EDTA or pharmaceutically acceptable salts thereof. 
     
     
         13 . The method of  claim 12 , wherein the composition contains less than 0.02% w/v EDTA, or pharmaceutically acceptable salts thereof. 
     
     
         14 . The method of  claim 13 , wherein the composition contains no EDTA, or pharmaceutically acceptable salts thereof. 
     
     
         15 . The method of claim  11  or  12 , wherein the pH of the composition is from 6 to 8. 
     
     
         16 . The method of  claim 15 , wherein the pH of the composition is from 6.5 to 7.0. 
     
     
         17 . The method of  claim 16 , wherein the pH of the composition is 6.8. 
     
     
         18 . The method of  claim 12 , wherein the administration occurs via intravenous injection, orally, or by inhalation. 
     
     
         19 . The method of  claim 18  wherein the method of administration occurs via intravenous injection. 
     
     
         20 - 32 . (canceled) 
     
     
         33 . A method of treating liver failure, comprising:
 using a stable aqueous pharmaceutical composition comprising from 10 to 250 mg/mL acetylcysteine or pharmaceutically acceptable salts thereof, wherein the composition contains less than 0.05% w/v chelating agents, wherein said composition is in a suitable form for intravenous administration;   diluting the composition in an aqueous solution; and   administering the diluted composition to a patient in need thereof.   
     
     
         34 . The method of  claim 33 , wherein the composition in an undiluted state comprises about 200 mg/mL acetylcysteine or pharmaceutically acceptable salts thereof. 
     
     
         35 . The method of  claim 33 , 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. 
     
     
         36 . The method of  claim 33 , wherein the composition is free of chelating agents.