Wound dressing and method for controlling severe, life-threatening bleeding

Abstract

This invention is directed to advanced hemorrhage control wound dressings, and methods of using and producing same. The subject wound dressing is constructed from a non-mammalian material for control of severe bleeding. The wound dressing for controlling severe bleeding is formed of a biomaterial comprising chitosan, a hydrophilic polymer, a polyacrylic polymer or a combination thereof. The kind of severe, life-threatening bleeding contemplated by this invention is typically of the type not capable of being stanched when a conventional gauze wound dressing is applied with conventional pressure to the subject wound. The wound dressing being capable of substantially stanching the flow of the severe life-threatening bleeding from the wound by adhering to the wound site, to seal the wound, to accelerate blood clot formation at the wound site, to reinforce clot formation at the wound site and prevent bleed out from the wound site, and to substantially prohibit the flow of blood out of the wound site.

1 . A compressed sponge for hemorrhage control comprising a hydrophilic polymer, wherein the compressed sponge has a compressed sponge density of about 0.6 to 0.15 g/cm 3 ; and 
 wherein the hydrophilic polymer is a polyacrylic acid.    
     
     
         2 . The compressed sponge of  claim 1 , wherein the compressed sponge further comprises an active ingredient.  
     
     
         3 . The compressed sponge of  claim 2 , wherein the active ingredient is calcium, thrombin, factor VIIa, factor XIII, thromboxane A2, prostaglandin-2a, epidermal growth factor, platelet derived growth factor, Von Willebrand factor, tumor necrosis factor (TNF), TNF-alpha, transforming growth factor (TGF), TGF-alpha, TGF-beta, insulin like growth factor, fibroblast growth factor, keratinocyte growth factor, nerve growth factor, penicillin, ampicillin, methicillin, amoxycillin, clavamox, clavulanic acid, amoxicillin, aztreonam, imipenem, streptomycin, Kanamycin, Tobramycin, gentamicin, vancomycin, clindamycin, erythromycin, polymyxin, bacitracin, amphotericin, nystatin, rifampicin, tetracycline, doxycycline, chloramphenicol or a combination thereof.  
     
     
         4 . A compressed composite sponge for hemorrhage control comprising a hydrophilic polymer sponge and a wettable polymer matrix or wettable polymer matrices inside the sponge and/or at the sponge surface; and wherein the hydrophilic polymer is polyacrylic acid.  
     
     
         5 . The compressed composite sponge of  claim 4 , wherein the wettable polymer matrices are selected from the group consisting of a non-woven mat, a woven mat, a molded polymer mesh, and a low density sponge.  
     
     
         6 . The compressed composite sponge of  claim 5 , wherein the wettable polymer matrix is selected from the group consisting of a chitin, an alginate, a neutralized chitosan, a re-acetylated chitosan, a poly(glycolic acid), a poly(lactic acid), a poly(e-caprolactone), a poly(β-hydroxybutyric acid), a poly(β-hydroxyvaleric acid), a polydioxanone, a poly(ethylene oxide), a poly(malic acid), a poly(tartronic acid), a polyphosphazene, a polyethylene, a polypropylene, a metallocene polymer, a polyurethane, a polyvinylchloride polymer, a polyester, a polyamide and a combination thereof.  
     
     
         7 . The compressed composite sponge of  claim 4 , wherein the sponge comprises a textile thread impregnated with a hydrophilic polymer.  
     
     
         8 . The compressed composite sponge of  claim 7 , wherein the textile thread is impregnated with a hydrophilic polymer, and wherein the hydrophilic polymer is a polyacrylic acid.  
     
     
         9 . The compressed composite sponge of  claim 4 , wherein the wettable polymer matrice is a non-woven mesh.  
     
     
         10 . The compressed composite sponge of  claim 4 , wherein the sponge contains pores with pore diameters of about 15 microns to about 300 microns.  
     
     
         11 . The compressed composite sponge of  claim 4 , wherein the sponge contains pores with pore diameters of about 30 microns to about 250 microns.  
     
     
         12 . The compressed composite sponge of  claim 4 , wherein the sponge contains pores with pore diameters of about 100 microns to about 225 microns.  
     
     
         13 . The compressed composite sponge of  claim 4 , wherein the sponge contains pores with pore diameters of about 125 microns to about 200 microns.  
     
     
         14 . The compressed composite sponge of  claim 4 , wherein the sponge contains pores with pore diameters of about 150 microns to about 175 microns.  
     
     
         15 . The compressed composite sponge of  claim 4 , wherein the sponge has an available blood contacting surface area per base surface of the sponge of about 100 cm 2  per cm 2  to about 1000 cm 2  per cm 2 .  
     
     
         16 . The compressed composite sponge of  claim 4 , wherein the sponge has an available blood contacting surface area per base surface of the sponge of about 200 cm 2  per cm 2  to about 800 cm 2  per cm 2 .  
     
     
         17 . The compressed composite sponge of  claim 4 , wherein the sponge has an available blood contacting surface area per base surface of the sponge of about 300 cm 2  per cm 2  to about 500 cm 2  per cm 2 .  
     
     
         18 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge further comprises a backing support layer.  
     
     
         19 . The compressed composite sponge of  claim 18 , wherein the backing support layer is a layer of polymeric material.  
     
     
         20 . The compressed composite sponge of  claim 19 , wherein the polymeric material is a synthetic biodegradable material or a naturally occurring biodegradable polymer.  
     
     
         21 . The compressed composite sponge of  claim 20 , wherein the synthetic biodegradable material is selected from the group consisting of poly(glycolic acid), poly(lactic acid), poly(e-caprolactone), poly(β-hydroxybutyric acid), poly(β-hydroxyvaleric acid), polydioxanone, poly(ethylene oxide), poly(malic acid), poly(tartronic acid), polyphosphazene, the copolymers of the monomers used to synthesize said polymers and combinations thereof.  
     
     
         22 . The compressed composite sponge of  claim 20 , wherein the naturally occurring biodegradable polymers are selected from the group consisting of chitin, algin, a starch, dextran, collagen, albumen, and combinations thereof.  
     
     
         23 . The compressed composite sponge of  claim 19 , wherein the synthetic non-biodegradable material is selected from the group consisting of polyethylene, polypropylene, a metallocene polymer, a polyurethane, a polyvinylchloride polymer, a polyester, a polyamide and a combination thereof.  
     
     
         24 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has a degree of adhesion to the wound site of about 40 kPa to 500 kPa.  
     
     
         25 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has a degree of adhesion to the wound site of about 60 kPa to 250 kPa.  
     
     
         26 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has a degree of adhesion to the wound site of about 100 kPa to 200 kPa.  
     
     
         27 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge is capable of forming an adhesive material in combination with blood flowing from said wound at a wound dressing-blood interface.  
     
     
         28 . The compressed composite sponge of  claim 27 , wherein the adhesive material preferably has a pH of not less than about 5.5 when the wound is sealed.  
     
     
         29 . The compressed composite sponge of  claim 27 , wherein the adhesive material preferably has a pH of not less than about 6.5 when the wound is sealed.  
     
     
         30 . The compressed composite sponge of  claim 27 , wherein the adhesive material preferably has a pH of not less than about 7.5 when the wound is sealed.  
     
     
         31 . The compressed composite sponge of  claim 27 , wherein the adhesive material comprises an acid selected from the group consisting of acetic acid, formic acid, lactic acid, ascorbic acid, hydrochloric acid and citric acid.  
     
     
         32 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has a thickness which is not less than about 3.0 mm and not more than about 8 mm.  
     
     
         33 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has a thickness which is not less than about 3.5 mm and not more than about 7 mm.  
     
     
         34 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has a thickness which is not less than about 4.0 mm and not more than about 6 mm.  
     
     
         35 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has an ultimate tensile stress about 0.1 MPa to about 10 MPa.  
     
     
         36 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has an ultimate tensile stress of about 0.15 MPa to about 0.8 MPa.  
     
     
         37 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has an ultimate tensile stress of about 0.25 MPa to about 0.5 Mpa.  
     
     
         38 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has an ultimate elongation of about 5%.  
     
     
         39 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has an ultimate elongation of about 10%.  
     
     
         40 . The compressed composite sponge of  claim 4 , wherein the compressed composite sponge has an ultimate elongation of about 15%.  
     
     
         41 . A process for preparing a compressed sponge for hemorrhage control of  claim 1  comprising: 
 (a) freezing/freeze drying a low density sponge; and    (b) compressing the low density sponge at about 10 mm per minute, and at about 80° C., to thereby obtain a compressed sponge with a density of about 0.1 to about 0.2 g/cm 3 .    
     
     
         42 . A process for preparing a compressed sponge for hemorrhage control of  claim 1  comprising: 
 (a) compressing a low density sponge at a rate of about 10 mm per minute, at about 80° C., to thereby obtain a compressed sponge with a density of about 0.1 to about 0.2 g/cm 3 , and wherein said low density sponge is not frozen or freeze-dried prior to compressing.    
     
     
         43 . The process of  claim 42 , wherein the low density sponge has a density of less than 0.035 g/cm 3  to about 0.01 g/cm 3 .  
     
     
         44 . The process of  claim 42 , wherein the compressed sponge has a density of about 0.15 g/cm 3  to about 0.1 g/cm 3 .  
     
     
         45 . A process for preparing a compressed composite sponge of  claim 4  for hemorrhage control comprising: 
 a) degassing a biomaterial solution by heating the biomaterial solution and applying a vacuum thereto;    b) freezing the degassed biomaterial solution;    c) removing water from within frozen biomaterial without damaging the structural integrity of the frozen biomaterial so that the water in the biomaterial passes from a solid phase into a gas phase;    d) compressing the biomaterial at a rate of about 10 mm per minute to obtain a compressed sponge with a density of about 0.1 to about 0.2 g/cm 3 ; and    e) baking the compressed sponge at 80 degrees C. for 30 minutes.    
     
     
         46 . The process of  claim 45 , wherein the temperature is gradually lowered over a predetermined period of time during the freezing of the biomaterial of step (b).  
     
     
         47 . The process of  claim 45 , wherein the temperature of step (b) is a final freezing temperature of not more than about −5° C.  
     
     
         48 . The process of  claim 45 , wherein the temperature of step (b) is a final freezing temperature of not more than about −35° C.  
     
     
         49 . The process of  claim 45 , wherein the temperature of step (b) is a final freezing temperature of not more than about −25° C.  
     
     
         50 . The process of  claim 45 , wherein the water removal is performed by freeze-drying the frozen biomaterial.  
     
     
         51 . The process of  claim 45 , further comprising the step of adding gases selected from the group consisting of argon, nitrogen and helium back into the degassed chitosan solution before the freezing.  
     
     
         52 . The process of  claim 45 , wherein the compressed sponge is sterilized.  
     
     
         53 . The process of  claim 45 , wherein the compressed sponge is sterilized by gamma irradiation.  
     
     
         54 . A method of preventing severe bleeding in a subject comprising administering a compressed sponge of  claim 1  or a compressed composite sponge of  claim 4 .  
     
     
         55 . The method of  claim 54 , wherein the subject is a mammal.  
     
     
         56 . The method of  claim 55 , wherein the mammal is human.  
     
     
         57 . The method of  claim 54 , wherein the subject is suffering from severe bleeding such that about 30-40% total blood loss would result within 20 to 30 minutes if the bleeding was left uncontrolled.  
     
     
         58 . The method of  claim 54 , wherein the compressed sponge or compressed composite sponge is applied with about 60 to 80 kPa pressure directly to a bleeding wound and held in place for 3 to 5 minutes before releasing, packing and wrapping the bleeding wound.  
     
     
         59 . A bandage kit for treating severe bleeding comprising the compressed sponges of  claim 1  or the composite compressed sponges of  claim 4 , a gauze roll for packing and an Ace bandage for wrapping a wound.  
     
     
         60 . A process for mechanical mating and meshing the sponges of claims  1  and  4  comprising pressing tissue contacting sides of the sponge against a macrotextured surface.  
     
     
         61 . The process of  claim 60 , wherein the macrotextured surface is selected from the group consisting of surfaces prepared by chemical etching, surfaces prepared by ion beam surface ablation, surfaces prepared by mechnical cutting, and surfaces prepared by laser ablation.  
     
     
         62 . A process for improving the mechanical traction of the sponges of claims  1  and  4  comprising pressing tissue contacting sides of the sponge against a macrotextured surface.  
     
     
         63 . The process of  claim 62 , wherein the microtextured surface is selected from the group consisting of surfaces prepared by chemical etching, and surfaces prepared by particle blasting techniques.  
     
     
         64 . A process for limiting or stopping the formation of coarse crust on the surface of a sponge of  claim 1  or  4 , comprising covering the surface of the sponge with a polymer film, a polymer plate, an elevated plastic plate, or a moisture impermeable, breathable membrane film.  
     
     
         65 . A compressed low density sponge, wherein a sponge with a density of about less than 0.05 g/cm 3  is compressed until the sponge reaches a density of about less than 0.08 g/cm 3 , and wherein the compressed, low density sponge is not frozen or freeze-dried prior to compression.  
     
     
         66 . The low density sponge of  claim 65 , wherein the sponge is subjected to a phase inversion process, a foaming technique or covalent binding of active components to preformed matrices prior to compression of the sponge.  
     
     
         67 . The compressed sponge and compressed composite sponge of  claim 1  or  4 , wherein the sponge further comprises a hydrophilic polymer.  
     
     
         68 . The compressed sponge and compressed composite sponge of  claim 67 , wherein the hydrophilic polymer is selected from the group consisting of alginate, chitosan, a hydrophilic polyamine, a chitosan derivative, polylysine, polyethylene imine, xanthan, carrageenan, quaternary ammonium polymer, chondroitin sulfate, a starch, a modified cellulosic polymer, a dextran, hyaluronan and a combination thereof.  
     
     
         69 . The compressed sponge and compressed composite sponge of  claim 68 , wherein the starch is selected from the group consisting of amylase, amylopectin and a combination of amylopectin and amylase.  
     
     
         70 . The compressed sponge and compressed composite sponge of  claim 67 , wherein the hydrophilic polymer is chitosan.