Treatment of interstitial cystitis using (6aR,10aR)-delta8-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 mammals suffering from interstitial cystitis using 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, the method comprising: 
 identifying a mammal suffering from or suspected of suffering from interstitial cystitis; and  
 administering to the mammal an effective amount of the compound of Formula II.  
 
     
     
         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 slow release of the compound.  
     
     
         14 . The method of  claim 1 , wherein the compound is administered intravenously.  
     
     
         15 . Use of a compound having Formula II or a pharmaceutically acceptable salt, ester, or solvate thereof for the preparation of a pharmaceutical composition for treating interstitial cystitis in a mammal,  
       
         
           
           
               
               
           
         
       
       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.  
     
     
         16 . The Use of  claim 15  in which the pharmaceutical composition further comprises an anticholinergic agent selected from the group consisting of anisotropine, aprophen, artane, atropine, belladonna, benactyzine, benztropine, clidinium, dicyclomine, glycopyrrolate, homatropine, hyoscyamine, isopropamide, mepenzolate, methantheline, methscopolamine, oxybutynin, oxyphencyclimine, propantheline, scopolamine, terodiline, tridihexethyl, trihexyphenidyl, and trospium.  
     
     
         17 . The Use of  claim 15  in which the pharmaceutical composition 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 . The Use of  claim 15  in which the pharmaceutical composition is formulated for oral administration.  
     
     
         19 . The Use of  claim 15  in which the pharmaceutical composition is formulated for administration via intravesicular instillation.  
     
     
         20 . Use of a compound having Formula III or a pharmaceutically acceptable salt, ester, or solvate thereof for the preparation of a pharmaceutical composition for  
       
         
           
           
               
               
           
         
       
       treating interstitial cystitis in a mammal.