Injectable resiniferatoxin

Abstract

The present invention provides compositions and methods for relieving pain at a site in a human or animal in need thereof by administering at a discrete site in a human or animal in need thereof a dose of capsaicin in an amount effective to denervate a discrete site without eliciting an effect outside the discrete location, the dose of capsaicin ranging from 1 μg to 3000 μg.

1 . A method for attenuating pain in a joint in a human or animal n need thereof, comprising:
 injecting into an intraarticular space of the joint a dose of a capsacinoid in an amount effective to denervate the joint without eliciting an effect systemically and to attenuate pain emanating from the joint, the effective dose being about 1 μg to about 5000 μg of capsaicin or a therapeutically equivalent dose of a capsaicinoid other than capsaicin.   
     
     
         2 . The method of  claim 1 , wherein the capsacinoid is resiniferatoxin. 
     
     
         3 . The method of  claim 2 , wherein the resiniferatoxin is administered in a pharmaceutically acceptable vehicle for injection. 
     
     
         4 . The method of  claim 1 , wherein the joint is selected from the group consisting of knee, elbow, hip, sternoclavicular, temporomandibular, carpal, tarsal, wrist, and ankle. 
     
     
         5 . The method of  claim 1 , further comprising administering a local anesthetic prior to or concurrently with the dose of capsacinoid in an amount and location effective to attenuate an initial hyperalgesic effect of the administered dose of capsacinoid. 
     
     
         6 . The method of  claim 4 , further comprising administering a local anesthetic prior to or concurrently with the dose of capsacinoid in an amount and location effective to attenuate an initial hyperalgesic effect of the administered dose of capsacinoid. 
     
     
         7 . The method of  claim 5 , wherein the local anesthetic is selected from the group consisting of dibucaine, bupivacaine, ropivacaine, etidocaine, tetracaine, procaine, chlorocaine, prilocaine, mepivacaine, lidocaine, xylocaine, 2-chloroprocaine, and acid addition salts or mixtures thereof. 
     
     
         8 . The method of  claim 7 , wherein the local anesthetic is administered to the site as a regional nerve block. 
     
     
         9 . The method of  claim 1 , wherein the pain is associated with a condition selected from the group consisting of osteoarthritis and rheumatoid arthritis. 
     
     
         10 . The method of  claim 1 , wherein the pain is associated with an injury selected from the group consisting of a tear of the anterior cruciate ligament, a tear of the posterior cruciate ligament, a tear of the medial collateral ligament, a tear of the lateral collateral ligament, a meniscal cartilage tear, and a cartilage defect of the knee. 
     
     
         11 . The method of  claim 1 , wherein said pain in a joint is associated with cancer pain. 
     
     
         12 . The method of  claim 1 , wherein from about 1×10 −5  mg/kg to about 5.0×10 −2  mg/kg of resiniferatoxin is administered to a human per injection. 
     
     
         13 . The method of  claim 6 , wherein from about 1×10  −5  mg/kg to about 5.0×10 −2  mg/kg of resiniferatoxin is administered to a human per injection. 
     
     
         14 . The method of  claim 1 , wherein method is for attenuating pain in the joint of a human. 
     
     
         15 . The method of  claim 4 , wherein method is for attenuating pain in the joint of a human. 
     
     
         16 . The method of  claim 5 , wherein method is for attenuating pain in the joint of a human, 
     
     
         17 . The method of  claim 9 , wherein method is for attenuating pain in the joint of a human. 
     
     
         18 . The method of  claim 1 , wherein the joint is a knee joint. 
     
     
         19 . The method of  claim 5 , wherein the joint is a knee joint. 
     
     
         20 . The method of  claim 9 , wherein the joint is a knee joint. 
     
     
         21 . The method of  claim 14 , wherein the joint is a knee joint. 
     
     
         22 . The method of  claim 16 , wherein the joint is a knee joint. 
     
     
         2 . 3 The method of  claim 17 , wherein the joint is a knee joint. 
     
     
         24 . An injectable or implantable pharmaceutical composition for attenuating pain at a site in a human or animal in need thereof, consisting essentially of a capsaicinoid selected from the group consisting of from 1 μg to about 5000 μg of capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and combinations thereof; in a pharmaceutically acceptable vehicle for injection or implantation. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein said pharmaceutically acceptable vehicle is an aqueous vehicle selected from the group consisting of Sodium Chloride Injection, Ringers Injection, Isotonic Dextrose Injection, Sterile Water Injection, Dextrose, Lactated Ringers Injection and any mixture thereof. 
     
     
         26 . The pharmaceutical composition of  claim 24 , wherein said pharmaceutically acceptable vehicle comprises effective concentrations of polyethylene glycol, histidine and sucrose, in water for injection. 
     
     
         27 . An injectable or implantable pharmaceutical composition for attenuating pain at a site in a human or animal in need thereof, consisting essentially of from 1 μg to about 5000 μg of trans-capsaicin and a pharmaceutically acceptable vehicle for injection or implantation. 
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein said pharmaceutically acceptable vehicle comprises effective concentrations of polyethylene glycol, histidine and sucrose, in water for injection.