Advanced functional biocompatible foam used as a hemostatic agent for compressible and non-compressible acute wounds

Abstract

A sprayable polymeric foam hemostat for both compressible and non-compressible (intracavitary) acute wounds is disclosed. The foam comprises hydrophobically-modified polymers, such as hm-chitosan, or other amphiphilic polymers that anchor themselves within the membrane of cells in the vicinity of the wound. By rapidly expanding upon being released from a canister pressurized with liquefied gas propellant, the foam is able to enter injured body cavities and staunch bleeding. The seal created is strong enough to substantially prevent the loss of blood from these cavities. Hydrophobically-modified polymers inherently prevent microbial infections and are suitable for oxygen transfer required during normal wound metabolism. The amphiphilic polymers form solid gel networks with blood cells to create a physical clotting mechanism that prevent loss of blood.

What is claimed is: 
     
         1 . An apparatus for the treatment of wounds, comprising:
 a valve system attached to a canister containing a hydrophobically modified alginate or cellulosic in a concentration of about 0.1% to about 2.0% by weight, wherein the hydrophobic modification of the alginate or cellulosic is of 1 to 100 moles of a hydrophobic substituent per 1 mole of alginate or cellulosic, and a propellant, wherein the hydrophobic modifications comprise hydrocarbon substituents of eight to twenty carbon residues in length covalently attached to alginate or cellulosic.   
     
     
         2 . The apparatus of  claim 1 , wherein the hydrophobically modified alginate or cellulosic is selected from the group consisting of alginate or cellulosic lactate, alginate or cellulosic salicylate, alginate or cellulosic pyrrolidone carboxylate, alginate or cellulosic itaconate, alginate or cellulosic niacinate, alginate or cellulosic formate, alginate or cellulosic acetate, alginate or cellulosic gallate, alginate or cellulosic glutamate, alginate or cellulosic maleate, alginate or cellulosic aspartate, alginate or cellulosic glycolate and quaternary amine substituted alginate or cellulosic and salts thereof. 
     
     
         3 . The apparatus of  claim 1 , wherein the canister further contains a plasticizing agent. 
     
     
         4 . The apparatus of  claim 3 , wherein the plasticizing agent is selected from the group consisting of glycerol, glycerophosphate, polyethylene glycol (PEG), polyethylene oxide (PEO), tripolyphosphate, polycaprolactone, polyurethane, and silicone. 
     
     
         5 . The apparatus of  claim 1 , wherein the canister contains a mixture of hydrophobically-modified alginate or cellulosic and glycerol in a ratio of 80:20 by weight. 
     
     
         6 . The apparatus of  claim 1 , wherein the propellant is selected from the group consisting of A70, CO 2 , N 2 , a noble gas such as helium, neon, argon, hydrocarbon gases, such as isopentane, isobutane, butane, and propane. 
     
     
         7 . The apparatus of  claim 1 , wherein the canister further contains a reagent that contribute to hemostatic integrity of a clot formed between the hydrophobically modified alginate or cellulosic and blood cells and tissues in a wound. 
     
     
         8 . The apparatus of  claim 7 , wherein the reagent is at least one of human thrombin, bovine thrombin, recombinant thrombin, Factor VIIa, Factor XIII, and human fibrinogen. 
     
     
         9 . The apparatus of  claim 1 , wherein the canister further contains an antimicrobial reagent. 
     
     
         10 . The apparatus of  claim 9 , wherein the antimicrobial agent is selected from the group consisting of ampicillin, penicillin, bacitracin, mupirocin, and neomycin, silver, vancomycin, ponericin G1, and norfloxacin. 
     
     
         11 . The apparatus of  claim 1 , wherein the hydrophobically modified alginate or cellulosic comprises 4-octadecyl benzene substituents in 2.5 mol % of monosaccharide units, in a concentration of 0.1 wt % to 0.8 wt %. 
     
     
         12 . The apparatus of  claim 1 , wherein the hydrophobically modified alginate or cellulosic comprises cis-oleoyl substituents in 2.5 mol % of monosaccharide units, in a concentration of 0.2 wt % to 1.5 wt %. 
     
     
         13 . The apparatus of  claim 1 , wherein the hydrophobically modified alginate or cellulosic is in a bag inside the canister and the propellant surrounds the bag. 
     
     
         14 . A method for delivery of a hemostat to a wound, comprising:
 applying a hydrophobically modified alginate or cellulosic to a wound from an apparatus, wherein said apparatus comprises a valve system attached to a canister containing the hydrophobically modified alginate or cellulosic in a concentration of about 0.1% to about 2.0% by weight and wherein the hydrophobic modification of the alginate or cellulosic is of 1 to 100 moles of a hydrophobic substituent per 1 mole of alginate or cellulosic, and a propellant, wherein the hydrophobic modifications comprise hydrocarbon substituents of eight to twenty carbon residues in length covalently attached to alginate or cellulosic.   
     
     
         15 . The method of  claim 14  wherein the hydrophobic substituent is an alkane. 
     
     
         16 . The method of  claim 14 , wherein the hydrophobically modified alginate or cellulosic is selected from the group consisting of alginate or cellulosic lactate, alginate or cellulosic salicylate, alginate or cellulosic pyrrolidone carboxylate, alginate or cellulosic itaconate, alginate or cellulosic niacinate, alginate or cellulosic formate, alginate or cellulosic acetate, alginate or cellulosic gallate, alginate or cellulosic glutamate, alginate or cellulosic maleate, alginate or cellulosic aspartate, alginate or cellulosic glycolate and quaternary amine substituted alginate or cellulosic and salts thereof. 
     
     
         17 . The method of  claim 14 , further comprising applying a plasticizing agent with the hydrophobically modified alginate or cellulosic. 
     
     
         18 . The method of  claim 17 , wherein the plasticizing agent is selected from the group consisting of glycerol, glycerophosphate, polyethylene glycol (PEG), polyethylene oxide (PEO), tripolyphosphate, polycaprolactone, polyurethane, and silicone. 
     
     
         19 . The method of  claim 14 , wherein a mixture of hydrophobically-modified alginate or cellulosic and glycerol in a ratio of 80:20 by weight is applied to the wound. 
     
     
         20 . The method of  claim 14 , further comprising applying a reagent that contributes to hemostatic integrity of a clot formed between the hydrophobically modified alginate or cellulosic and blood cells and tissues in a wound. 
     
     
         21 . The method of  claim 20 , wherein the reagent is at least one of human thrombin, bovine thrombin, recombinant thrombin, Factor VIIa, Factor XIII, and human fibrinogen. 
     
     
         22 . The method of  claim 14 , further comprising applying an antimicrobial reagent to a wound with the hydrophobically modified alginate or cellulosic. 
     
     
         23 . The method of  claim 22 , wherein the antimicrobial reagent is selected from the group consisting of ampicillin, penicillin, bacitracin, mupirocin, and neomycin, silver, vancomycin, ponericin G1, and norfloxacin. 
     
     
         24 . The method of  claim 14 , wherein the hydrophobically modified alginate or cellulosic comprises 4-octadecyl benzene substituents in 2.5 mol % of monosaccharide units, in a concentration of 0.1 wt % to 0.8 wt %. 
     
     
         25 . The method of  claim 14 , wherein the hydrophobically modified alginate or cellulosic comprises cis-oleoyl substituents in 2.5 mol % of monosaccharide units, in a concentration of 0.2 wt % to 1.5 wt %. 
     
     
         26 . An apparatus for the treatment of wounds, comprising:
 a valve system attached to a canister containing a hydrophobically modified alginate or cellulosic in a concentration of about 0.1% to about 2.0% by weight, wherein the hydrophobic modification of the alginate or cellulosic is of 1 to 100 moles of a hydrophobic substituent per 1 mole of alginate or cellulosic, and a propellant, wherein the hydrophobic modification of alginate or cellulosic comprises 4-octadecyl benzene covalently attached to the alginate or cellulosic.