Oral cannabinoid receptor modulator formulations

Abstract

Oral formulations of benzofuran compounds which modulate cannabinoid receptors are presented. Methods of using these formulations for treatment of cannabinoid receptor-mediated disease, including neuropathic pain and addition, are also described.

We claim the following: 
     
         1 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier suitable for oral administration and a compound according to Formula I 
       
         
           
           
               
               
           
         
       
       or a salt, ester or prodrug thereof, wherein:
 R 1  is selected from the group consisting of NH 2 , NHR 4 , and NR 4 R 5 , any carbon atom of R 1  of which may be optionally substituted; 
 R 2  is selected from the group consisting of hydrogen, aryl, alkyl, cycloalkyl, aralkyl, alkenyl, and alkynyl, any carbon atom of which may be optionally substituted; 
 R 3  is selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, aryl, and heteroaryl, any carbon atom of which may be optionally substituted; and 
 R 4  and R 5  and are selected from the group consisting of aryl, alkyl, cycloalkyl, aralkyl, alkenyl, and alkynyl, any carbon atom of which may be optionally substituted, wherein the pharmaceutically acceptable carrier is a hydroxypropyl methylcellulose polymer. 
 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         5 . (canceled) 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the hydroxypropyl methylcellulose polymer of the pharmaceutically acceptable carrier is a spray-dried polymer dispersion. 
     
     
         7 . (canceled) 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the polymer is hydroxypropyl methylcellulose acetate succinate (HPMCAS). 
     
     
         9 . A method of treatment of a cannabinoid receptor-mediated disease comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition according to  claim 1 . 
     
     
         10 . The method of  claim 9 , wherein the pharmaceutically acceptable carrier suitable for oral administration comprises HPMCAS. 
     
     
         11 . The method of  claim 9 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         12 . A method of treating neuropathic pain in a subject, said method comprising administering to the subject having or susceptible to said pain or pain-associated disorder, a therapeutically-effective amount of a pharmaceutical composition according to  claim 1 . 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12 , wherein the pharmaceutically acceptable carrier suitable for oral administration comprises HPMCAS. 
     
     
         15 . The method of  claim 12 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         16 . A method of treating addiction in a subject, comprising administering to the subject having or susceptible to said addiction or addiction-related disorder, a therapeutically-effective amount of a pharmaceutical composition according to  claim 1 . 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 16 , wherein the pharmaceutically acceptable carrier suitable for oral administration comprises HPMCAS. 
     
     
         19 . The method of  claim 16 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The composition of  claim 1 , wherein the pharmaceutically acceptable carrier is a hydroxypropyl methylcellulose acetate succinate subtype M (HPMCAS-M) or subtype H (HPMCAS-H) spray-dried dispersion. 
     
     
         21 . The composition of  claim 1 , wherein the compound is 25% (wt) of the pharmaceutical composition. 
     
     
         22 . The method of  claim 9 , wherein the pharmaceutically acceptable carrier is a hydroxypropyl methylcellulose acetate succinate subtype M (HPMCAS-M) or subtype H (HPMCAS-H) spray-dried dispersion. 
     
     
         23 . The method of  claim 9 , wherein the compound is 25% (wt) of the pharmaceutical composition. 
     
     
         24 . The method of  claim 12 , wherein the pharmaceutically acceptable carrier is a hydroxypropyl methylcellulose acetate succinate subtype M (HPMCAS-M) or subtype H (HPMCAS-H) spray-dried dispersion. 
     
     
         25 . The method of  claim 12 , wherein the compound is 25% (wt) of the pharmaceutical composition. 
     
     
         26 . The method of  claim 16 , wherein the pharmaceutically acceptable carrier is a hydroxypropyl methylcellulose acetate succinate subtype M (HPMCAS-M) or subtype H (HPMCAS-H) spray-dried dispersion. 
     
     
         27 . The method of  claim 16 , wherein the compound is 25% (wt) of the pharmaceutical composition. 
     
     
         28 . A method of treating a neurodegenerative disease in a subject, comprising administering to the subject having or susceptible to said neurodegenerative disease or neurodegenerative disease-related disorder, a therapeutically-effective amount of a pharmaceutical composition according to  claim 1 . 
     
     
         29 . The method of  claim 28 , wherein the pharmaceutically acceptable carrier suitable for oral administration comprises HPMCAS. 
     
     
         30 . The method of  claim 28 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
     
     
         31 . The method of  claim 28 , wherein the pharmaceutically acceptable carrier is a hydroxypropyl methylcellulose acetate succinate subtype M (HPMCAS-M) or subtype H (HPMCAS-H) spray-dried dispersion. 
     
     
         32 . The method of  claim 28 , wherein the compound is 25% (wt) of the pharmaceutical composition.