Tumescent contravenom drug delivery

Abstract

A tumescent contravenom solution including: (a) a vasoconstrictor, (b) a physiological crystalloid solution, and (c) optionally a contravenom agent that neutralizes tissue toxic enzymes present in a venom and/or a drug that impairs or paralyzes lymphatic smooth muscle function and impairs lymphatic transport of venom. Also described are methods of treating an envenomation in a subject, and a kit for performing the method of treating an envenomation.

What is claimed is: 
     
         1 . A tumescent contravenom solution comprising:
 (a) a vasoconstrictor, and   (b) a physiological crystalloid solution.   
     
     
         2 . The tumescent contravenom solution according to  claim 1 , further comprising a contravenom agent that neutralizes tissue toxic enzymes present in a venom. 
     
     
         3 . The tumescent contravenom solution according to  claim 2 , wherein the contravenom is selected from the group consisting of a hyaluronidase inhibitor, a proteinase inhibitor, a metalloproteinase chelating agent, a phospholipase A2 inhibitor, a cellular receptor site blocker, a platelet activator and a platelet activation inhibitor. 
     
     
         4 . The tumescent contravenom solution according to  claim 3 , wherein the phospholipase A2 inhibitor is Varespladib or a salt thereof. 
     
     
         5 . The tumescent contravenom solution according to  claim 4 , wherein the salt of Varespladib is a sodium salt. 
     
     
         6 . The tumescent contravenom solution according to  claim 2 , wherein contravenom neutralizes a venom from an organism selected from the group consisting of a Cnidarian, a jellyfish, a sea anemone, a hydra, a mollusk, an annelid, an arthropod, a spider, a scorpion, a centipede, a bee, a wasp, an ant, a tick, a horsefly, an echinoderm, a starfish, a sea urchin, and a venomous vertebrate, including a fish, an amphibian, a snake, a lizard and a mammal. 
     
     
         7 . The tumescent contravenom solution according to  claim 1 , wherein the vasoconstrictor is epinephrine. 
     
     
         8 . The tumescent contravenom solution according to  claim 7 , wherein the epinephrine is at a concentration of 0.2 to 1.5 mg/L. 
     
     
         9 . The tumescent contravenom solution according to  claim 1 , further comprising a drug that impairs or paralyzes lymphatic smooth muscle function and impairs lymphatic transport of venom. 
     
     
         10 . The tumescent contravenom solution according to  claim 1 , further comprising a local anesthetic. 
     
     
         11 . The tumescent contravenom solution according to  claim 10 , wherein the local anesthetic is lidocaine. 
     
     
         12 . The tumescent contravenom solution according to  claim 11 , wherein lidocaine is at a concentration of 0.4 mg/ml to 1.2 mg/ml. 
     
     
         13 . The tumescent contravenom solution according to  claim 1 , further comprising a beta-blocker drug that slows heart rate, thereby limiting systemic distribution of venom. 
     
     
         14 . The tumescent contravenom solution according to  claim 2 , wherein the concentration of contravenom agent is diluted by a factor of 2 or more by the physiological crystalloid solution, or wherein a volume used to dissolve a lyophilized powder of the contravenom agent is at least twice a minimal amount required to dissolve the contravenom agent. 
     
     
         15 . The tumescent contravenom solution according to  claim 1 , wherein the physiological crystalloid solution is selected from the group consisting of 0.9% physiologic saline and lactated Ringer's solution. 
     
     
         16 . A method of treating an envenomation in a subject comprising locally injecting the tumescent contravenom solution according to  claim 1  within and/or around a site of the envenomation. 
     
     
         17 . The method according to  claim 16 , comprising self-administering of the tumescent contravenom solution by the subject. 
     
     
         18 . The method according to  claim 16 , wherein the tumescent contravenom solution is injected subcutaneously or intramuscularly. 
     
     
         19 . The method according to  claim 16 , wherein the contravenom solution is injected within 5-10 minutes following the envenomation. 
     
     
         20 . A kit for performing the method according to  claim 16  comprising:
 (a) a physiological crystalloid solution, 
 (b) a vasoconstrictor that is either in solid or liquid form, 
 (c) a hypodermic needle or an infiltration cannula, and 
 (d) a syringe. 
 
     
     
         21 . The kit according to  claim 20 , further comprising a contravenom agent and/or a drug that impairs or paralyzes lymphatic smooth muscle function and impairs lymphatic transport of venom.