Infiltration of capsaicin into surgical sites and open wounds

Abstract

The present invention provides compositions and methods for attenuating or relieving pain at a site in a human or animal in need thereof by infiltrating at a surgical site or open wound in a human or animal a dose of capsaicinoid in an amount effective to denervate the surgical site or open wound substantially without eliciting an effect outside the surgical site or open wound.

1 . A method for attenuating pain at a surgical site or an open wound in a human or animal, comprising: 
 infiltrating a dose of a capsaicinoid in an amount effective to denervate a site selected from a surgical site or an open wound without eliciting an effect outside the site, said effective dose being from about 1 μg to about 15,000 μg of capsaicin or a therapeutically equivalent dose of a capsaicinoid other than capsaicin.    
     
     
         2 . The method of  claim 1 , wherein said dose of capsaicin is from about 600 to about 15,000 μg.  
     
     
         3 . The method of  claim 1 , wherein said dose of capsaicin is from about 600 to about 10,000,μg.  
     
     
         4 . The method of  claim 1 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for infiltration in a volume from about 0.1 to about 1000 ml.  
     
     
         5 . The method of  claim 1 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for infiltration in a volume from about 1 ml to about 100 ml.  
     
     
         6 . The method of  claim 1 , wherein said dose of capsaicinoid is administered in a pharmaceutically acceptable vehicle for infiltration in a volume from about 5 ml to about 30 ml.  
     
     
         7 . The method of  claim 4 , 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 combinations or mixtures thereof.  
     
     
         8 . The method of  claim 7 , wherein said pharmaceutically acceptable vehicle comprises an agent selected form the group consisting of antimicrobial agents, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, emulsifying agents, sequestering, chelating agents and any combinations thereof.  
     
     
         9 . The method of  claim 5 , wherein said pharmaceutically acceptable vehicle comprises about 20% PEG 300, about 10 mM histidine and about 5% sucrose in water for injection.  
     
     
         10 . The method of  claim 1 , wherein said dose of capsaicinoid is administered in the form of microparticles selected from the group consisting of microcapsules and microspheres.  
     
     
         11 . The method of  claim 1 , further comprising administering a local anesthetic prior to or concurrently with said dose of capsaicinoid in an amount and location effective to attenuate an initial hyperalgesic effect of said administered dose of capsaicinoid.  
     
     
         12 . The method of  claim 11 , wherein said 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.  
     
     
         13 . The method of  claim 11 , wherein said local anesthetic is administered by infiltration to the surgical or wound site.  
     
     
         14 . The method of  claim 1 , further comprising administering general anesthesia to the human or animal prior to infiltration of said dose of capsaicinoid.  
     
     
         15 . The method of  claim 1 , wherein said administration of capsaicinoid at the site provides attenuation of pain in proximity to the surgical or wound site for at least about 48 hours.  
     
     
         16 . The method of  claim 1 , wherein said administration of capsaicinoid at the site provides attenuation of pain in proximity to the surgical or wound site for at least about one week.  
     
     
         18 . The method of  claim 1 , wherein said capsaicinoid comprises capsaicin.  
     
     
         19 . The method of  claim 1 , wherein said dose comprises a capsaicinoid other than capsaicin.  
     
     
         20 . The method of  claim 19 , wherein said capsaicinoid is selected from the group consisting of resiniferatoxin, N-vanillylnonanamides, N-vanillylsulfonarnides, N-vanillylureas, N-vanillylcarbamates, N[(substituted phenyl)methyl]alkylamides, methylene substituted N[(substituted phenyl)methyl]alkanamides, N[(substituted phenyl) methyl]- cis-monosaturated alkenamides, N[(substituted phenyl)methyl]diunsaturated amides, 3-hydroxyacetanilide, hydroxyphenylacetamides, pseudocapsaicin, dihydrocapsaicin, nordihydrocapsaicin anandamide, piperine, zingerone, warburganal, polygodial, aframodial, cinnamodial, cinnamosmolide, cinnamolide, isovelleral, scalaradial, ancistrodial, β-acaridial, merulidial, scutigeral, and any combinations thereof.  
     
     
         21 . The method of  claim 20 , wherein said capsaicinoid is resiniferatoxin.  
     
     
         22 . The method of  claim 18 , wherein said capsaicin consists essentially of trans-capsaicin.  
     
     
         23 . The method of  claim 1 , wherein said capsaicinoid administration provides an effect selected from the group consisting of: a) producing a selective, highly-localized destruction or incapacitation of C-fibers and/or A-delta fibers in a localized area responsible for the initiation of pain for the purpose of reducing or eliminating pain arising from the area, and b) minimizing potential adverse consequences of C-fiber and/or A-delta activation and or damage outside of the locus of pain.  
     
     
         24 . The method of  claim 1 , wherein said surgical site is a median sternotomy, and the method further comprises infiltrating said dose of capsaicinoid in an amount effective to denervate said sternal edges without eliciting an effect outside the sternal edge location.  
     
     
         25 . The method of  claim 1 , wherein said wound is a long bone fracture.  
     
     
         26 . The method of  claim 1 , wherein said surgical site is a laparoscopy.  
     
     
         27 . The method of  claim 1 , wherein said surgical site is a mastectomy.  
     
     
         28 . The method of  claim 1 , wherein said surgical site is an arthroplasty.  
     
     
         29 . The method of  claim 28 , wherein said dose of capsaicinoid is from about 500 μg to about 5000 μg capsaicin, or a therapeutically equivalent dose of another capsaicinoid.  
     
     
         28 . The method of  claim 1 , wherein said surgical site is associated with cancer surgery.  
     
     
         29 . The method of  claim 1 , wherein said surgical site is a bunionectomy, and said dose of capsaicinoid is from about 500 μg to about 2000 μg capsaicin, or a therapeutically equivalent dose of another capsaicinoid.  
     
     
         30 . The method of  claim 1 , wherein said surgical site 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; a cartilage defect of the knee; and combinations of any of the foregoing.  
     
     
         31 . The method of  claim 1 , wherein said surgical site is associated with an orthopedic disorder of the shoulder selected from the group consisting of bursitis, dislocation, separation, impingement and tear of the rotator cuff, tendonitis, adhesive capsulitis, shoulder fracture, and combinations of any of the foregoing.  
     
     
         42 . The method of  claim 1 , wherein said surgical site is associated with tendonitis, bursitis or bursitis injury.  
     
     
         42 . The method of  claim 1 , wherein the capsaicinoid is a purified capsaicin.  
     
     
         43 . The method of  claim 42 , wherein the capsaicinoid is at least about 97% trans-capsaicin.  
     
     
         44 . An pharmaceutical composition for attenuating pain at a surgical site in a human or animal in need thereof, comprising a capsaicinoid selected from the group consisting of from 1 μg to 15,000 μg of capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and therapeutically equivalent combinations thereof, in from about 1 ml to about 100 ml of a pharmaceutically acceptable vehicle for infiltration.  
     
     
         45 . The pharmaceutical composition of  claim 44 , wherein said capsaicinoid comprises from about 500 μg to 5000 μg capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and therapeutically equivalent combinations thereof.  
     
     
         49 . The pharmaceutical composition of  claim 44 , wherein the capsaicinoid is at least about 97% trans-capsaicin.  
     
     
         50 . The method of  claim 44 , wherein said pharmaceutically acceptable vehicle comprises effective concentrations of polyethylene glycol, histidine and sucrose, in water for injection.  
     
     
         51 . The method of  claim 44 , said capsaicinoid comprises greater than 5001 μg to about 15,000 μg capsaicin, a therapeutically equivalent amount of one or more other capsaicinoids, and therapeutically equivalent combinations thereof.