Cysteine composition and injection

Abstract

Cysteine compositions comprising less than about 400 μg/L of aluminum. For example, solutions of cysteine comprising a pharmaceutically acceptable solvent, cysteine, and less than about 145 μg/L of aluminum, wherein the solution is devoid of visible particulate matter. Cysteine compositions described herein may be suitable for injection. For example, disclosed cysteine solutions may be provided intravenously to meet amino acid nutritional requirement in individuals receiving total parenteral nutrition. Also provided are processes for preparing cysteine compositions, and methods for providing cysteine to individuals in need thereof.

1 . A process for preparing a solution of cysteine hydrochloride, the process comprising:
 acidifying water to a pH from about 1.0 to about 1.5 to form acidified water;   dissolving cysteine hydrochloride in the acidified water to form a solution; and   filling and sealing a container with the solution, wherein the solution is disposed under flow of an inert gas during the filling and sealing.   
     
     
         2 . The process of  claim 1 , wherein the acidifying is performed under flow of an inert gas. 
     
     
         3 . The process of  claim 1 , wherein the acidifying comprises adding hydrochloric acid. 
     
     
         4 . The process of  claim 1 , wherein the pH of the acidified water is from about 1.0 to about 1.3. 
     
     
         5 . The process of  claim 1 , further comprising sparging the water with an inert gas to achieve a dissolved oxygen content of less than about 2 mg/L in the water prior to the acidifying. 
     
     
         6 . The process of  claim 1 , wherein the dissolving comprises adding about 40 mg to about 60 mg of cysteine hydrochloride per 1 mL of acidified water. 
     
     
         7 . The process of  claim 1 , wherein the dissolving comprises adding about 50 mg of cysteine hydrochloride per 1 mL of acidified water. 
     
     
         8 . The process of  claim 1 , wherein the dissolving comprises stirring the cysteine hydrochloride and the acidified water under flow of an inert gas. 
     
     
         9 . The process of  claim 1 , further comprising checking and adjusting, if necessary, the pH of the solution to a value from about 1.0 to about 1.5 prior to the filling and sealing. 
     
     
         10 . The process of  claim 1 , further comprising sterile filtering the solution prior to the filling and sealing. 
     
     
         11 . The process of  claim 10 , wherein the sterile filtering comprises passing the solution through at least one 0.22 μm filter. 
     
     
         12 . The process of  claim 1 , wherein the acidifying, the dissolving, and the filling and sealing are performed at ambient temperature. 
     
     
         13 . The process of  claim 1 , wherein the acidifying occurs prior to the dissolving. 
     
     
         14 . The process of  claim 1 , wherein the container is a silica-lined glass vial. 
     
     
         15 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has a pH from about 1.0 to about 1.5. 
     
     
         16 . The process of  claim 1 , wherein the solution of cysteine hydrochloride comprises about 50 mg/mL of cysteine hydrochloride. 
     
     
         17 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is free of visible particulate matter. 
     
     
         18 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has a cystine content of less than about 1% by weight of the total cysteine present in the solution of cysteine hydrochloride. 
     
     
         19 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has a cystine content of less than about 0.5% by weight of the total cysteine present in the solution of cysteine hydrochloride. 
     
     
         20 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has a dissolved oxygen content of less than about 2 mg/L. 
     
     
         21 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has an aluminum content of less than about 145 μg/L. 
     
     
         22 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is stable when stored for at least six months at 25° C. and 60% relative humidity. 
     
     
         23 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is stable when stored for at least 12 months at 25° C. and 60% relative humidity. 
     
     
         24 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is stable when stored for at least 18 months at 25° C. and 60% relative humidity. 
     
     
         25 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is stable when stored for at least 24 months at 25° C. and 60% relative humidity. 
     
     
         26 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is free of visible particulate matter when stored for at least six months at 25° C. and 60% relative humidity. 
     
     
         27 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is free of visible particulate matter when stored for at least 12 months at 25° C. and 60% relative humidity. 
     
     
         28 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is free of visible particulate matter when stored for at least 18 months at 25° C. and 60% relative humidity. 
     
     
         29 . The process of  claim 1 , wherein the solution of cysteine hydrochloride is free of visible particulate matter when stored for at least 24 months at 25° C. and 60% relative humidity. 
     
     
         30 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has an aluminum content of less than about 145 μg/L when stored for at least six months at 25° C. and 60% relative humidity. 
     
     
         31 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has an aluminum content of less than about 145 μg/L when stored for at least 12 months at 25° C. and 60% relative humidity. 
     
     
         32 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has an aluminum content of less than about 145 μg/L when stored for at least 18 months at 25° C. and 60% relative humidity. 
     
     
         33 . The process of  claim 1 , wherein the solution of cysteine hydrochloride has an aluminum content of less than about 145 μg/L when stored for at least 24 months at 25° C. and 60% relative humidity. 
     
     
         34 .- 65 . (canceled) 
     
     
         66 . A solution of cysteine hydrochloride comprising about 40 mg/mL to about 60 mg/mL of cysteine hydrochloride and a pH from about 1.0 to about 1.5, wherein the cysteine hydrochloride solution is prepared by a process comprising:
 acidifying water to a pH from about 1.0 to about 1.5 to form acidified water;   dissolving about 40 mg to about 60 mg of cysteine hydrochloride per 1 mL of acidified water to form the solution; and   filling and sealing a container in which the solution is disposed under flow of an inert gas.   
     
     
         67 . A cysteine hydrochloride solution comprising about 50 mg/mL of cysteine hydrochloride and having a pH from about 1.0 to about 1.5, wherein the cysteine hydrochloride solution is prepared by a process comprising:
 acidifying water to a pH from about 1.0 to about 1.5 to form acidified water; and   dissolving about 50 mg of cysteine hydrochloride per 1 mL of acidified water to form the cysteine hydrochloride solution.   
     
     
         68 . The process of  claim 1 , further comprising checking that the solution of cysteine hydrochloride has a dissolved oxygen content of less than about 2 mg/L and, if necessary, adjusting the dissolved oxygen content prior to the filling and sealing. 
     
     
         69 . The process of  claim 68 , wherein the adjusting comprises sparging the solution of cysteine hydrochloride with an inert gas to achieve the dissolved oxygen content of less than about 2 mg/L. 
     
     
         70 . A solution of cysteine comprising about 10 mg/mL to about 100 mg/mL of cysteine prepared by acidifying water to a pH from about 1.0 to about 1.5 to form acidified water and dissolving about 10 mg/mL to about 100 mg/mL of cysteine per 1 mL of acidified water to form the solution, wherein the solution of cysteine has a pH from about 1.0 to about 1.5. 
     
     
         71 . A solution of cysteine comprising about 10 mg/mL to about 100 mg/mL of cysteine and less than about 1% of cystine by weight of the total cysteine present in the solution, wherein the solution has a pH from about 1.0 to about 1.5 and the solution is devoid of visible particulate matter.