(R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij]quinolin-2(1H)-one maleate

Abstract

The sustained release tablet of (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1) which is disclosed permits twice daily administration of (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1) to treat humans with Parkinson's disease.

1 . A pharmaceutical composition which is a sustained release tablet for oral ingestion which comprises:  
       
         
           
                 
                 
               
                     
                 
                     
                 
                   (a) (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]- 
                   0.3%-16%  
                 
                     quinolin-2(1H)-one (Z)-2-butenedioate (1:1) 
                 
                   (b) starch 
                   60%-69% 
                 
                   (c) hydroxypropyl methylcellulose 
                   30%-40% 
                 
                     
                 
                     
                 
             
                
                
               
               
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . A pharmaceutical composition according to    claim 1    which comprises:  
       
         
           
                 
                 
               
                     
                 
                     
                 
                   (a) (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]- 
                   0.44%-10%   
                 
                     quinolin-2(1H)-one (Z)-2-butenedioate (1:1) 
                 
                   (b) pregelatinized or corn starch 
                   60%-67% 
                 
                   (c) hydroxypropyl methylcellulose 
                   30%-40% 
                 
                     
                 
                     
                 
             
                
                
               
               
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . A pharmaceutical composition according to    claim 1    where (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1) is present in an amount from about 0.3% (1 mg) to about 16% (56 mg) /tablet.  
     
     
         4 . A pharmaceutical composition according to    claim 1    where (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1) is present in an amount of about 0.44% (1.5 mg), 0.88% (3.1 mg), 1.76% (6.2 mg), 3.52% (12.3 mg) and 5.33% (19 mg) /tablet.  
     
     
         5 . A pharmaceutical composition according to    claim 1    where the starch is pregelatinized or corn starch.  
     
     
         6 . A pharmaceutical composition according to    claim 1    where the starch is a mixture of pregelatinized and corn starch.  
     
     
         7 . A pharmaceutical composition according to    claim 1    where the hydroxypropyl methylcellulose is selected from the group consisting of 
 hydroxypropyl methylcellulose 2208 USP 100 cps,  
 hydroxypropyl methylcellulose 2208 USP 4,000 cps,  
 hydroxypropyl methylcellulose 2208 USP 15,000 cps,  
 hydroxypropyl methylcellulose 2208 USP 100,000 cps,  
 hydroxypropyl methylcellulose 2910 USP 4,000 cps,  
 hydroxypropyl methylcellulose 2910 USP 10,000 cps, or mixtures thereof.  
 
     
     
         8 . A pharmaceutical composition according to    claim 7    where the hydroxypropyl methylcellulose is hydroxypropyl methylcellulose 2208 USP 4,000 cps or hydroxypropyl methylcellulose 2910 USP 4,000 cps.  
     
     
         9 . A pharmaceutical composition according to    claim 1    which contains magnesium stearate.  
     
     
         10 . A pharmaceutical composition according to    claim 9    where the magnesium stearate is present in an amount of from about 0.2 to about 2.0%.  
     
     
         11 . A pharmaceutical composition according to    claim 1    which contains colloidal silicon dioxide.  
     
     
         12 . A pharmaceutical composition according to    claim 11    where the colloidal silicon dioxide is present in an amount of from about 0.2 to about 1.0%.  
     
     
         13 . A pharmaceutical composition according to    claim 1    where the tablet is about 350 mg in total weight.  
     
     
         14 . A method of treating humans who have Parkinson's disease which comprises orally administering an anti-Parkinson's effective amount of (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2(1H)-one (Z)-2-butenedioate (1:1).  
     
     
         15 . A method of treating humans who have Parkinson's disease according to    claim 14    where the (R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5-ij]-quinolin-2( [H)-one (Z)-2-butenedioate (1:1) is administered twice daily.  
     
     
         16 . A method of treating humans who have Parkinson's disease according to    claim 14    where the effective amount is from about 2 mg to about 112 mg/day.  
     
     
         17 . A method of treating humans who have Parkinson's disease according to    claim 16    where the effective amount is from about 3 mg to about 70 mg/day.