Continuous administration of l-dopa, dopa decarboxylase inhibitors, catechol-o-methyl transferase inhibitors and compositions for same

Abstract

Provided herein, in part, is a method of treating a neurological or movement disorder in a patient in need thereof, comprising subcutaneously administering to said patient a pharmaceutically acceptable composition comprising levodopa and optionally carbidopa and optionally entacapone or tolcapone, or pharmaceutically acceptable salts thereof, wherein said composition is administered substantially continuously, and compositions that can be used in the disclosed methods.

1 - 34 . (canceled) 
     
     
         35 . A pharmaceutically acceptable formulation comprising about 2.5 to about 7% by weight levodopa, about 0 to about 2% by weight carbidopa, about 5 to about 18% by weight arginine, and about 0.25% to about 3% by weight ascorbic acid or a pharmaceutically acceptable salt thereof. 
     
     
         36 . A pharmaceutically acceptable formulation comprising (i) about 8 to about 12% by weight levodopa, about 1 to about 3% by weight carbidopa, and about 15 to about 35% weight arginine; or (ii) about 8 to about 12% by weight levodopa, about 1 to about 3% by weight carbidopa, about 12 to about 15% weight arginine, and about 3% to about 10% by weight meglumine. 
     
     
         37 . The pharmaceutically acceptable formulation of  claim 36 , further comprising about 0.25-3% by weight ascorbic acid. 
     
     
         38 . A pharmaceutically acceptable liquid composition comprising arginine and entacapone or tolcapone. 
     
     
         39 . The pharmaceutically acceptable liquid composition of  claim 38 , comprising at least about 2%, at least about 4%, or at least about 2% to about 12%, by weight entacapone or tolcapone. 
     
     
         40 . The pharmaceutically acceptable liquid composition of  claim 38 , wherein the entacapone and the arginine or the tolcapone and the arginine have a molar ratio of about 1:0.5 to about 1:2.5, or about 1:1 to about 1:1.5. 
     
     
         41 . The pharmaceutically acceptable liquid composition of  claim 38 , wherein the pH of the liquid composition is about 6 to about 9 at 25° C., or the liquid composition is substantially stable at 25° C. for 48 hours or more. 
     
     
         42 . The pharmaceutically acceptable liquid composition of  claim 38 , further comprising a pharmaceutically acceptable excipient. 
     
     
         43 . The pharmaceutically acceptable formulation of  claim 36 , wherein said formulation is suitable for substantially continuous subcutaneous, intraduodenal or intravenous administration. 
     
     
         44 . A process for preparing a stable liquid solution comprising levodopa and/or carbidopa, and arginine, comprising:
 providing levodopa and/or carbidopa, and arginine to form a powder mixture;   adding water to said powder mixture to form a suspension;   heating said suspension at a temperature of about 40° C. to about 90° C. to form a solution; and   cooling said solution to provide the stable liquid composition.   
     
     
         45 . The process of  claim 44 , wherein heating said suspension further comprises stirring the suspension. 
     
     
         46 - 47 . (canceled) 
     
     
         48 . A method of treating a neurological disorder or a movement disorder in a patient in need thereof, the method comprising administering the composition of  claim 35  to the patient.