Therapeutic compositions and methods of treatment with capsianoside-type compounds

Abstract

The present invention discloses the use of certain compounds as therapeutic agents, and in particular as analgesics and anti-inflammatory agents. Such compounds include, for example, certain diterpene monoglycosides and diterpene diglycosides. The compounds of the present invention may be synthesized or isolated from the fruit of the genus Capsicum , and in particular may be isolated from sweet bell peppers ( C. annuum ). Pharmaceutically-acceptable salts, enantiomers, diasteriomers, racemic mixtures, enantiomerically-enriched mixtures, solvates, and prodrugs of such compounds are also disclosed. Pharmaceutical compositions and methods of using such compounds, including pharmaceutical compositions and methods of using such compounds in combination with one or more active ingredients, are also disclosed.

1 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to Formula I:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-acceptable salt, enantiomer, diasteriomer, racemic mixture, enantiomerically-enriched mixture, solvate, or prodrug of Formula I in a pharmaceutically effective carrier,  
       wherein 
 R 1  is a carbohydrate moiety;  
 R 2  is H or C(O)R 4 ;  
 R 3  is H, a carbohydrate moiety, or a substituted or unsubstituted C 1 -C 20  group; and  
 R 4  is a substituted or unsubstituted C 1 -C 20  group.  
 
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein said compound is present in an amount that is therapeutically effective to effect analgesia or reduce inflammation in a mammal.  
     
     
         3 . A pharmaceutical composition according to  claim 1 , wherein each of R 1  and R 3  is independently selected from the group consisting of a glucose moiety, a galactose moiety, a rhamnose moiety, a xylose moiety, and an arabinose moiety.  
     
     
         4 . A pharmaceutical composition according to  claim 1 , wherein each of R 2 , R 3 , and R 4  independently comprises one or more aromatic rings.  
     
     
         5 . A pharmaceutical composition according to  claim 1 , wherein said compound according to Formula I is a compound of Formula II:  
       
         
           
           
               
               
           
         
       
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein said prodrug of a compound according to Formula I is a compound according to Formula III:  
       
         
           
           
               
               
           
         
         , wherein R 5  is a hydrolyzable sugar.  
       
     
     
         7 . A pharmaceutical composition according to  claim 6 , wherein said hydrolyzable sugar is glucose.  
     
     
         8 . A pharmaceutical composition according to  claim 1 , wherein said prodrug of a compound according to Formula I is a compound of Formula IV:  
       
         
           
           
               
               
           
         
       
     
     
         9 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to Formula II:  
       
         
           
           
               
               
           
         
       
       or a compound according to Formula IV:  
       
         
           
           
               
               
           
         
       
       in a pharmaceutically effective carrier, 
 wherein said compound according to Formula II or Formula IV is present in an amount that is therapeutically effective to effect analgesia or reduce inflammation in a mammal.  
 
     
     
         10 . A pharmaceutical composition according to  claim 9 , wherein said composition is in a form selected from the group consisting of: an immediate-release composition, a controlled-release composition, sustained-release orally-administrable compositions, topically-administrable compositions, liquid solutions, liquid sprays, lozenges, throat sprays, ointments, solutions, foams, cough drops, dissolvable strips, a jelly, a mouthwash; a gargle, a lollipop, a gum, aequeous or oily suspensions, dispersible powders or granules, a syrup, an elixir, emulsions, a cream, a paste, a gel, a lotion, impregnated dressings, occularly-administrable compositions, inhalable particles, inhalable solutions, droplets, and aerosols.  
     
     
         11 . A pharmaceutical composition according to  claim 9 , wherein said compound according to Formula II or IV is produced synthetically, semi-synthetically, or is isolated and purified from a naturally occurring organism.  
     
     
         12 . A pharmaceutical composition according to  claim 9 , further comprising one or more therapeutic agents in combination with said compound according to Formula II or IV, said therapeutic agents being selected from the group consisting of analgesics, NSAIDs, salicylates, acetaminophen, ibuprofen, and COX-2 inhibitors.  
     
     
         13 . A pharmaceutical composition according to  claim 9 , wherein said amount that is therapeutically effective to effect analgesia or reduce inflammation in a mammal is between about 0.01 mg to about 500 mg per unit dose, or between about 1 mg to about 100 mg per unit dose.  
     
     
         14 . A method for effecting analgesia and/or reducing inflammation in a mammal, comprising administering to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound according to Formula I:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-acceptable salt, enantiomer, diasteriomer, solvate, or prodrug of Formula I, in a pharmaceutically effective carrier,  
       wherein 
 R 1  is a carbohydrate moiety;  
 R 2  is H or C(O)R 4 ;  
 R 3  is H, a carbohydrate moiety, or a substituted or unsubstituted C 1 -C 20  group; and  
 R 4  is a substituted or unsubstituted C 1 -C 20  group.  
 
     
     
         15 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 14 , wherein said compound is present in an amount that is therapeutically effective to effect analgesia or reduce inflammation in a mammal.  
     
     
         16 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 14 , wherein each of R 1  and R 3  is independently selected from the group consisting of glucose, galactose, rhamnose, xylose, and arabinose.  
     
     
         17 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 14 , wherein each of R 2 , R 3 , and R 4  independently comprises one or more aromatic rings.  
     
     
         18 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 14 , wherein said compound according to Formula I is a compound of Formula II:  
       
         
           
           
               
               
           
         
       
     
     
         19 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 14 , wherein said prodrug of a compound according to Formula I is a compound according to Formula III:  
       
         
           
           
               
               
           
         
       
       , wherein R 5  is a hydrolyzable sugar.  
     
     
         20 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 19 , wherein said hydrolyzable sugar is glucose.  
     
     
         21 . A method for effecting analgesia and/or reducing inflammation in a mammal according to  claim 14 , wherein said prodrug of a compound according to Formula I is a compound of Formula IV:  
       
         
           
           
               
               
           
         
       
     
     
         22 . A method for effecting analgesia and/or reducing inflammation in a mammal, comprising administering to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound isolated and purified from a fruit of the genus  Capsicum , wherein said compound is present in an amount that is therapeutically effective to effect analgesia or reduce inflammation in a mammal.