Methods of Treating Wounds With Gonyautoxins

Abstract

Pharmaceutical compositions comprising tricyclic 3,4-propinoperhydropurines and uses thereof for blocking neuronal transmission which are useful in treating anal fissure and other wounds and muscle disorders are provided. Also provided are methods of treating wounds and muscle disorders by administering the composition of the invention to a muscle or in the vicinity of a muscle either topically or by injection.

1 . A method of facilitating the healing of a wound comprising the step of administering to a patient in need of such treatment an effective amount of a composition comprising at least one tricyclic 3,4-propinoperhydropurine represented by formula (I) set forth below:  
     
       
         
         
             
             
         
       
     
     wherein R 1  and R 5  are independently selected from the group consisting of —H and —OH; R 2  and R 3  are independently selected from the group consisting of —H and —SO 3 ; 
 and R 4  is selected from the group consisting of —H, —OH, —COONH 2 , —COONHSO −   3  and —COOCH 3 , with the proviso that either one of R 2  and R 3  must be —OSO −   3 , or R 4  must be —COONHSO −   3 , and a pharmacologically acceptable carrier.  
 
   
   
       2 . The method of  claim 1 , wherein the composition is injected into a muscle.  
   
   
       3 . The method of  claim 1 , where in the method is applied to a patient afflicted with anal fissure.  
   
   
       4 . The method of  claim 1 , wherein the at least one compound of the formula (I) is selected from the group consisting of: GTX-1, GTX-2, GTX-3, GTX-4 and GTX-5.  
   
   
       5 . The method of  claim 1 , wherein the composition comprises both GTX-2 and GTX-3.  
   
   
       6 . The method of  claim 1 , wherein the effective amount of said composition contains from about 1 to about 1000 units of activity.  
   
   
       7 . The method of  claim 1 , wherein the effective amount of said composition contains from more than 32 to about 1000 units of activity.  
   
   
       8 . The method of  claim 1 , wherein the effective amount of said composition contains from about 50 to about 1000 units of activity.  
   
   
       9 . The method of  claim 1 , wherein the effective amount of said composition contains from about 50 to about 500 units of activity.  
   
   
       10 . The method of  claim 1 , wherein the effective amount of said composition contains from about 75 to about 200 units of activity.  
   
   
       11 . The method of  claim 1 , wherein said composition further comprises a neurotoxin selected from the group consisting of saxitoxin, neosaxitoxin, decarbamoylsaxitoxin, tetanus toxin, and Botulin A toxin.  
   
   
       12 . The method of  claim 1 , wherein said composition further comprises a local anesthetic.  
   
   
       13 . The method of  claim 12 , wherein the local anesthetic is selected from the group consisting of: benzocaine, tetracaine, mepivacaine, prilocaine, etidocaine, bupivacaine, lidocaine.  
   
   
       14 . The method of  claim 1 , wherein the composition is injected into the internal anal sphincter.  
   
   
       15 . The method of  claim 1 , wherein the method is applied to a patient afflicted with at least one ailment selected from the group consisting of achalasia, and anal fissure.  
   
   
       16 . The method of  claim 1 , wherein the method is applied to a patient with a wound for the purpose of facilitating the healing of the wound.  
   
   
       17 . The method of  claim 15 , wherein the effective amount of said composition contains from about 50 to about 1000 units of activity.  
   
   
       18 . The method of  claim 16 , wherein the effective amount of said composition contains from about 50 to about 1000 units of activity.  
   
   
       19 . The method of  claim 1 , wherein the composition is applied topically.  
   
   
       20 . The method of  claim 19 , wherein the topical composition comprises from about 0.0001% to about 0.01% by weight of one or more compounds of the formula I, based on the total weight of the composition.