Methods of treating parkinson's disease

Abstract

The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.

1 . An aqueous pharmaceutical composition comprising:
 (a) a first compound corresponding in structure to Formula (I):   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein R 1  is —P(O)(OH) 2 ; R 2  is hydrogen, R 6  is hydrogen or a C 1 -C 4 -alkyl; and
 (b) a second compound corresponding in structure Formula (II): 
 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein R 3  is —P(O)(OH) 2 ; R 4  is hydrogen, R 6  is hydrogen or a C 1 -C 4 -alkyl. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the first compound or pharmaceutically acceptable salt thereof, and the second compound or pharmaceutically acceptable salt thereof are present in separate pharmaceutical compositions. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the first compound or pharmaceutically acceptable salt thereof, and the second compound or pharmaceutically acceptable salt thereof are present in a same pharmaceutical composition. 
     
     
         4 - 7 . (canceled) 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the first compound is 
       
         
           
           
               
               
           
         
       
       and the second compound is 
       
         
           
           
               
               
           
         
       
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein a weight ratio of the first compound or pharmaceutically acceptable salt thereof to the second compound or pharmaceutically acceptable salt thereof is from about 1:4 to about 1:10. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the composition is suitable for intragastric, subcutaneous, intramuscular, intrajejunum, oral, intranasal or intravenous administration. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the combination is an aqueous combination suitable for subcutaneous administration. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the first compound or pharmaceutically acceptable salt thereof has a solubility of at least about 200 mg/ml in aqueous solution at about neutral pH, and the second compound or pharmaceutically acceptable salt thereof has a solubility of at least about 400 mg/ml in aqueous solution at about neutral pH. 
     
     
         13 .- 18 . (canceled) 
     
     
         19 . A method of treating Parkinson's disease comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to  claim 1 . 
     
     
         20 . The method of  claim 19 , wherein the first compound and the second compound are administered in separate pharmaceutical compositions. 
     
     
         21 . The method of  claim 19 , wherein the first compound and the second compound are administered in a same pharmaceutical composition. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 19 , further comprising administering another anti-Parkinson's agent to the subject. 
     
     
         24 . The method of  claim 19 , wherein the pharmaceutical combination is an aqueous combination. 
     
     
         25 . The method of  claim 24 , wherein the aqueous pharmaceutical combination is administered by intragastric, subcutaneous, intramuscular, intranasal, intrajejunum, oral or intravenous administration. 
     
     
         26 . The method of  claim 25 , wherein the aqueous pharmaceutical composition is administered by subcutaneous administration. 
     
     
         27 . The method of  claim 26 , wherein the method comprises substantially continuous administration of the pharmaceutical composition over a period of at least about 12 hours. 
     
     
         28 . (canceled) 
     
     
         29 . A kit comprising the pharmaceutical composition of  claim 1 . 
     
     
         30 . (canceled)