Ultrapure tetrahydrocannabinol-11-oic acids

Abstract

This application is in the field of medicinal chemistry and relates to ultrapure ajulemic acid, its synthesis, pharmaceutical compositions and methods of use thereof for the treatment and/or prevention of inflammation, pain, and fibrotic diseases including scleroderma, systemic sclerosis, scleroderma-like disorders, sine scleroderma, liver cirrhosis, interstitial pulmonary fibrosis, idiopathic pulmonary fibrosis, Dupuytren's contracture, keloids, chronic kidney disease, chronic graft rejection, and other scarring-wound healing abnormalities, post-operative adhesions, and reactive fibrosis.

1 . A composition comprising ajulemic acid, wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 2 times to about 100 times greater than the affinity for the CB1 receptor. 
     
     
         2 . The composition of  claim 1 , wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 5 times to about 50 times greater than the affinity for the CB1 receptor. 
     
     
         3 . The composition of  claim 2 , wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 10 times to about 40 times greater than the affinity for the CB1 receptor. 
     
     
         4 . The composition of  claim 1 , wherein the ajulemic acid has a purity of greater than about 97%. 
     
     
         5 . The composition of  claim 4 , wherein the ajulemic acid has a purity of greater than about 98%. 
     
     
         6 . The composition of  claim 5 , wherein the ajulemic acid has a purity of greater than about 99%. 
     
     
         7 - 18 . (canceled) 
     
     
         19 . A composition comprising ajulemic acid, wherein the ajulemic acid has less than about 0.1% (w/w) of 11-hydroxy-(6aR,10aR)-3-(1′,1′-dimethylheptyl)-′8-tetrahydrocannabinol (HU-210). 
     
     
         20 . The composition of  claim 19 , wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 2 times to about 100 times greater than the affinity for the CB1 receptor. 
     
     
         21 . The composition of  claim 20 , wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 5 times to about 50 times greater than the affinity for the CB1 receptor. 
     
     
         22 . The composition of  claim 21 , wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 20 times to about 40 times greater than the affinity for the CB1 receptor. 
     
     
         23 . A method of treating a subject with fibrotic disease comprising the step of administering a therapeutically effective amount of ajulemic acid to the subject, wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 2-fold to about 100-fold greater than the affinity for the CB1 receptor. 
     
     
         24 . The method of  claim 23 , wherein the fibrotic disease is dermal fibrosis. 
     
     
         25 . The method of  claim 24 , wherein the fibrotic disease is lung fibrosis. 
     
     
         26 . The method of  claim 23 , wherein the fibrotic disease is selected from the group consisting of scleroderma, systemic sclerosis, scleroderma-like disorders, sine scleroderma, liver cirrhosis, interstitial pulmonary fibrosis, idiopathic pulmonary fibrosis, Dupuytren's contracture, keloids, cystic fibrosis, chronic kidney disease, chronic graft rejection, and other scarring/wound healing abnormalities, post-operative adhesions, and reactive fibrosis. 
     
     
         27 . The method of  claim 23 , wherein the ajulemic acid is administered orally. 
     
     
         28 . The method of  claim 23 , wherein the ajulemic acid is administered intravenously. 
     
     
         29 . The method of  claim 23 , wherein the ajulemic acid is administered topically. 
     
     
         30 . The method of  claim 23 , wherein the ajulemic acid is administered ophthalmically. 
     
     
         31 . The method of  claim 23 , wherein the ajulemic acid is administered via an implant or patch. 
     
     
         32 . A method of reducing pain in a subject comprising the step of administering a composition comprising ajulemic acid to the subject, wherein the ajulemic acid has an affinity for the CB2 receptor ranging from about 2-fold to about 100-fold greater than the affinity for the CB1 receptor. 
     
     
         33 . The method of  claim 32 , wherein the pain is reduced by at least 1 point on an 11-point pain scale. 
     
     
         34 . (canceled)