Method of Treating or Preventing Pain

Abstract

Compounds for use in the treatment or prophylaxis of pain, including acute and chronic pain (e.g., nociceptive pain, neuropathic pain, headaches, migraine), represented by general formula I: in which: the dotted line represents a single or a double bond; and R 5 and R 5 ′ are independently —H, —OH or —OR 6 , where R 6 is a linear or branched C 1 -C 4 alkyl; X is —CH 2 O—; Z is —CH 2 CH 2 O—, —CH(CH 3 )CH 2 O— or —CH 2 CH(CH 3 )O—; m is 1; and n is an integer of 1-5. The compounds of the invention are also effective for reducing inflammation and may be used alone or in combination with other analgesics.

1 . A method for treating or preventing pain in a human or non-human animal patient in need thereof, which method comprises administering to said patient a therapeutically effective amount of at least one compound represented by formula I: 
       
         
           
           
               
               
           
         
         wherein: 
            represents a single or a double bond; 
         R 5  and R 5 ′ are independently —H, —OH or —OR 6 , wherein R 6  is a linear or branched C 1 -C 4  alkyl; 
         X is —CH 2 O—; 
         Z is —CH 2 CH 2 O—, —CH(CH 3 )CH 2 O— or —CH 2 CH(CH 3 )O—; 
         m is 1; and 
         n is an integer of 1, 2, 3, 4, or 5; 
         or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof. 
       
     
     
         2 . The method as claimed in  claim 1  for the treatment of acute or chronic pain. 
     
     
         3 . The method as claimed in  claim 1  for the treatment of nociceptive pain or neuropathic pain. 
     
     
         4 . The method as claimed in  claim 1 , wherein the compound is represented by formula II: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt prodrug, metabolite, or hydrate thereof. 
       
     
     
         5 . The method as claimed in  claim 1 , wherein Z is —CH 2 CH(CH 3 )O—. 
     
     
         6 . The method as claimed in  claim 4 , wherein the compound is represented by formula III: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof. 
       
     
     
         7 . The method as claimed in  claim 1 , wherein R 5  is H or OH. 
     
     
         8 . The method as claimed in  claim 1 , wherein R 5 ′ is H or OH. 
     
     
         9 . The method as claimed in  claim 6 , wherein n is 1 or 2. 
     
     
         10 . The method as claimed in  claim 1 , wherein the compound is represented by formula IV, V, VI or VII: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof, 
         wherein R is a polyalkylene glycol polymer having n units, wherein n is an integer of 1, 2, 3, 4, or 5. 
       
     
     
         11 . The method as claimed in  claim 1 , wherein the compound is administered as a pharmaceutical composition comprising a therapeutically effective amount of one or more of the compounds represented by formula I together with one or more pharmaceutically acceptable excipients. 
     
     
         12 . The method as claimed in  claim 11 , wherein the composition comprises said one or more compounds in substantially pure form, said substantially pure form consisting of at least 95% wt. of said one or more compounds and up to 5% wt. of free polyalkylene glycol, with the total amount in said form of said one or more compounds and said free polyalkylene glycol being 100% wt. 
     
     
         13 . The method as claimed in  claim 11 , wherein the composition comprises said one or more compounds in partially pure form, said partially pure form consisting of about 5-60% wt. of the one or more compounds and about 95-40% wt. of free polyalkylene glycol, the total amount being 100% wt. 
     
     
         14 . The method as claimed in  claim 11 , wherein the composition is formulated as a unit dosage form. 
     
     
         15 . The method as claimed in  claim 11 , wherein the composition is formulated for oral administration. 
     
     
         16 . The method as claimed in  claim 11 , wherein the composition is formulated as a unit dosage form comprising from 0.1 to about 500 mg of the one or more compounds. 
     
     
         17 . The method as claimed in  claim 11 , wherein a daily dose of 1.0 mg to 15 g of said one or more compounds is administered. 
     
     
         18 . The method as claimed in  claim 11 , wherein the one or more compounds are administered orally.