Treatment of interstitial cystitis using (6aR, 10aR)-delta-8-tetrahydrocannabinol-11-oic acids

Abstract

The present invention relates to non-psychoactive derivatives of tetrahydrocannabinol, which are useful in treating interstitial cystitis and relieving symptoms thereof. The invention uses (6aR,10aR)-Δ 8 -tetrahydrocannabinol-11-oic acids (hereinafter referred to as (6aR,10aR)-Δ 8 -THC-11-oic acid), as well as pharmaceutical compositions containing the (6aR,10aR)-Δ 8 -THC-11-oic acids, for treatment of interstitial cystitis in a mammal. The invention further covers methods of formulating and administering the compounds and pharmaceutical compositions as therapeutic agents in the treatment of interstitial cystitis, with particularly preferred administration routes being oral and via intravesicular instillation.

1 . A method of treating a mammal suffering from interstitial cystitis comprising administering to the mammal a therapeutically effective amount of a compound having Formula II 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen, —COCH 3  or —COCH 2 CH 3 ; R 2  is a branched C 5 -C 12  alkyl compound, which may optionally have a terminal aromatic ring, or optionally a branched —OCHCH 3 (CH 2 ) m  alkyl compound, which may have a terminal aromatic ring, wherein m is 0 to 7, or a pharmaceutically acceptable salt, ester, or solvate thereof. 
       
     
     
         2 . The method of  claim 1 , wherein R 1  is hydrogen. 
     
     
         3 . The method of  claim 2 , wherein R 2  is a C 9  alkyl. 
     
     
         4 . The method of  claim 3 , wherein the C 9  alkyl is a branched alkyl. 
     
     
         5 . The method of  claim 4 , wherein the branched alkyl is 1,1-dimethylheptyl. 
     
     
         6 . The method of  claim 1 , wherein R 2  is a C 9  alkyl. 
     
     
         7 . The method of  claim 6 , wherein the C 9  alkyl is a branched alkyl. 
     
     
         8 . The method of  claim 7 , wherein the branched alkyl is 1,1-dimethylheptyl. 
     
     
         9 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         10 . The method of  claim 1 , wherein the compound is administered orally. 
     
     
         11 . The method of  claim 1 , wherein the compound is administered via intravesicular instillation. 
     
     
         12 . The method of  claim 1 , wherein the compound is administered via an implant. 
     
     
         13 . The method of  claim 12 , wherein the implant provides a slow release of the compound. 
     
     
         14 . The method of  claim 1 , wherein the compound is administered intravenously. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1  wherein the compound is administered in a pharmaceutical composition which further comprises an anticholinergic agent selected from the group consisting of anisotropine, aprophen, artane, atropine, belladonna, benactyzine, benztropine, clidinium, dicyclomine, glycopyrrolate, homatropine, hyoscyamine, isoprapamide, mepenzolate, methantheline, methscopolamine, oxybutynin, oxyphencyclimine, propantheline, scopolamine, terodiline, tridihexethyl, trihexyphenidyl, and trospium. 
     
     
         17 . The method of  claim 1  wherein the compound is administered in a pharmaceutical composition which further comprises an agent useful in relieving symptoms of interstitial cystitis selected from the group consisting of sodium pentosanpolysulfate, antihistamines, antidepressants, imipramine, antispasmodics, urinary anesthetics, capsaicin, DMSO, heparin, hyaluronic acid, Cystitat, silver nitrate, chlorpactin, and BCG. 
     
     
         18 - 20 . (canceled) 
     
     
         21 . The method of  claim 5 , wherein the mammal is human. 
     
     
         22 . The method of  claim 5 , wherein the compound is administered orally. 
     
     
         23 . The method of  claim 5 , wherein the compound is administered via intravesicular instillation. 
     
     
         24 . The method of  claim 5 , wherein the compound is administered via an implant. 
     
     
         25 . The method of  claim 24 , wherein the implant provides slow release of the compound. 
     
     
         26 . The method of  claim 5 , wherein the compound is administered intravenously. 
     
     
         27 . The method of  claim 1 , wherein the compound is a compound having Formula II 
       
         
           
           
               
               
           
         
         wherein R 1  is hydrogen and R 2  is 1,1-dimethylheptyl.