Hemostatic compositions and devices

Abstract

The present invention includes both sterilized and unsterilized hemostatic compositions that contain a continuous, biocompatible liquid phase having a solid phase of particles of a biocompatible polymer suitable for use in hemostasis and which is substantially insoluble in the liquid phase, and a discontinuous, biocompatible gaseous phase, each of which is substantially homogenously dispersed throughout the continuous liquid phase, methods for making such compositions, medical devices that contain sterilized hemostatic compositions disposed therein and methods of making such devices.

1 . A hemostatic composition, comprising: 
 a continuous, biocompatible liquid phase,    a solid phase comprising particles of a biocompatible polymer suitable for use in hemostasis and which is substantially insoluble in said liquid phase; and    a discontinuous gaseous phase comprising a biocompatible gas, said continuous liquid phase comprising said solid phase and said discontinuous gaseous phase substantially homogenously dispersed there through, wherein the ratio of said liquid phase, said solid phase and said gaseous phase is effective to provide said composition with hemostatic properties.    
     
     
         2 . The composition of  claim 1  wherein said liquid phase is aqueous.  
     
     
         3 . The composition of  claim 2  wherein said liquid phase comprises saline.  
     
     
         4 . The composition of  claim 3  wherein said biocompatible polymer is selected from the group consisting of proteins and polysaccharides.  
     
     
         5 . The composition of  claim 4  wherein said protein is selected from the group consisting of gelatin, collagen, fibrinogen and fibronectin.  
     
     
         6 . The composition of  claim 5  wherein said protein comprises gelatin.  
     
     
         7 . The composition of  claim 6  wherein the average diameter of said particle is from about 40 to about 1200 microns.  
     
     
         8 . The composition of  claim 7  wherein said particles, said liquid phase and said gaseous phase are present in said hemostatic composition at a ratio of from about 1:2:1 to about 1:12:13, based on g:ml:ml.  
     
     
         9 . The composition of  claim 8  wherein said particles, said liquid phase and said gaseous phase are present in said hemostatic composition at a ratio of from about 1:4:1 to about 1:8:9, based on g:ml:ml.  
     
     
         10 . The composition of  claim 8  wherein the density of said composition is from about 0.9 g/ml to about 0.3 g/ml.  
     
     
         11 . The composition of  claim 9  wherein the density of said composition is from about 0.8 g/ml to about 0.6 g/ml.  
     
     
         12 . The composition of  claim 1  wherein said gas is selected from the group consisting of air, nitrogen, carbon dioxide, xenon and argon.  
     
     
         13 . The composition of  claim 1  further comprising a functionally effective amount of an additive selected from the group consisting of antimicrobial agents, foaming agents, foam stabilizers, surfactants, antioxidants, humectants, thickeners, diluents, lubricants, wetting agents, irradiation stabilizers, plasticizers, heparin neutralizers, procoagulants and hemostatic agents.  
     
     
         14 . The composition of  claim 13  comprising up to about 20 percent by weight of glycerol, based on the weight of said liquid phase.  
     
     
         15 . The composition of  claim 13  comprising up to about 1 percent by weight of a quaternary amine, based on the weight of said liquid phase.  
     
     
         16 . The composition of  claim 15  comprising from about 0.001% to about 0.01% by weight of benzalkonium chloride, based on the weight of said liquid phase  
     
     
         17 . The composition of  claim 1  wherein said composition is sterile.  
     
     
         18 . The composition of  claim 13  wherein said composition is sterile.  
     
     
         19 . The composition of  claim 18  wherein said functional additive is selected from the group consisting of fibrinogen and thrombin.  
     
     
         20 . A method for making a substantially homogenous hemostatic composition suitable for use in hemostatic devices suitable for applying a flowable hemostatic composition to a site requiring hemostatis, said method comprising: 
 providing a biocompatible liquid, particles of a biocompatible polymer suitable for use in hemostasis and which is substantially insoluble in said liquid, and a biocompatible gas,    combining said liquid, said particles and said gas; and    mixing said liquid, said particles and said gas under conditions effective to form a continuous liquid phase comprising said particles and a discontinuous gaseous phase substantially homogenously dispersed there through, thereby forming said substantially homogeneous hemostatic composition,    wherein the ratio of said continuous liquid phase, said particles and said gaseous phase is effective to provide said composition with hemostatic properties.    
     
     
         21 . The method of  claim 20  wherein said liquid phase comprises saline.  
     
     
         22 . The method of  claim 21  wherein said biocompatible polymer is selected from the group consisting of proteins and polysaccharides.  
     
     
         23 . The method of  claim 22  wherein said protein is selected from the group consisting of gelatin, collagen, fibrinogen and fibronectin.  
     
     
         24 . The method of  claim 23  wherein said protein comprises gelatin.  
     
     
         25 . The method of  claim 24  wherein the average diameter of said particle is from about 40 to about 1200 microns.  
     
     
         26 . The method of  claim 24  wherein said particles, said liquid phase and said gaseous phase are combined at a ratio of from about 1:2:1 to about 1:12:13, based on g:ml:ml.  
     
     
         27 . The method of  claim 26  wherein the density of said substantially homogenous hemostatic composition is from about 0.9 g/ml to about 0.3 g/ml.  
     
     
         28 . The method of  claim 20  wherein said gas is selected from the group consisting of air, nitrogen, carbon dioxide, xenon and argon.  
     
     
         29 . The method of  claim 20  further comprising adding to said liquid phase a functionally effective amount of an additive selected from the group consisting of antimicrobial agents, foaming agents, foam stabilizers, surfactants, antioxidants, humectants, lubricants, thickeners, diluents, wetting agents, irradiation stabilizers, heparin neutralizers, procoagulants and hemostatic agents.  
     
     
         30 . The method of  claim 29  wherein up to about 20 weight percent of glycerol are added to said liquid, based on the weight of said liquid.  
     
     
         31 . The method of  claim 29  wherein up to about 1 weight percent of a quaternary amine is added to said liquid, based on the weight of said liquid.  
     
     
         32 . The method of  claim 20  further comprising irradiating said substantially homogeneous composition with an amount of ionizing irradiation and for a time effective to provide a sterile, substantially homogeneous composition.  
     
     
         33 . The method of  claim 29  further comprising irradiating said substantially homogeneous composition with an amount of ionizing irradiation and for a time effective to provide a sterile, substantially homogeneous composition.  
     
     
         34 . The method of  claim 33  wherein said additive is selected from the group consisting of fibrinogen and thrombin.  
     
     
         35 . A medical device suitable for applying a flowable hemostatic composition to a site requiring hemostatis, said device having disposed therein a substantially homogeneous hemostatic composition, said substantially homogeneous hemostatic composition comprising: 
 a continuous, biocompatible liquid phase,    a solid phase comprising particles of a biocompatible polymer suitable for use in hemostasis and which is substantially insoluble in said liquid phase; and    a discontinuous gaseous phase comprising a biocompatible gas, said continuous liquid phase comprising said solid phase and said discontinuous gaseous phase substantially homogenously dispersed there through, wherein the ratio of said liquid phase, said solid phase and said gaseous phase is effective to provide said composition with hemostatic properties.    
     
     
         36 . The device of  claim 35  wherein said liquid phase comprises saline.  
     
     
         37 . The device of  claim 35  wherein said biocompatible polymer is selected from the group consisting of proteins and polysaccharides.  
     
     
         38 . The device of  claim 37  wherein said protein is selected from the group consisting of gelatin, collagen, fibrinogen and fibronectin.  
     
     
         39 . The device of  claim 38  wherein said protein comprises gelatin.  
     
     
         40 . The device of  claim 39  wherein the average diameter of said particle is from about 40 to about 1200 microns.  
     
     
         41 . The device of  claim 35  wherein said particles, said continuous liquid phase and said gaseous phase are present in said substantially homogeneous hemostatic composition at a ratio of from about 1:2:1 to about 1:12:13, based on g:ml:ml.  
     
     
         42 . The device of  claim 41  wherein the density of said substantially homogeneous hemostatic composition is from about 0.9 g/ml to about 0.3 g/ml.  
     
     
         43 . The device of  claim 35  wherein said gas is selected from the group consisting of air, nitrogen, carbon dioxide, xenon and argon.  
     
     
         44 . The device of  claim 35  wherein said composition further comprises a functionally effective amount of an additive selected from the group consisting of antimicrobial agents, foaming agents, foam stabilizers, surfactants, antioxidants, humectants, thickeners, lubricants, diluents, wetting agents, irradiation stabilizers, plasticizers, heparin neutralizers, procoagulants and hemostatic agents.  
     
     
         45 . The device of  claim 44  wherein said composition comprises up to about 20 weight percent of glycerol, based on the weight of said liquid phase.  
     
     
         46 . The device of  claim 44  wherein said composition comprises up to about 1 weight percent of a quaternary amine, based on the weight of said liquid phase.  
     
     
         47 . The device of  claim 35  wherein said composition and said device are sterile.  
     
     
         48 . The device of  claim 44  wherein said composition and said device are sterile.  
     
     
         49 . The device of  claim 48  wherein said functional additive is selected from the group consisting of fibrinogen and thrombin.  
     
     
         50 . A method for making a medical device suitable for applying a flowable hemostatic composition to a site requiring hemostasis, the method comprising: 
 providing a substantially homogeneous hemostatic composition, said composition comprising a continuous, biocompatible liquid phase, a solid phase comprising particles of a biocompatible polymer suitable for use in hemostasis and which is substantially insoluble in said liquid phase, and a discontinuous gaseous phase comprising a biocompatible gas, said continuous liquid phase comprising said solid phase and said discontinuous gaseous phase substantially homogenously dispersed there through, wherein the ratio of said liquid phase, said solid phase and said gaseous phase is effective to provide said composition with hemostatic properties; and    dispensing said substantially homogeneous hemostatic composition into said medical device.    
     
     
         51 . The method of  claim 50  wherein said liquid phases comprises saline.  
     
     
         52 . The method of  claim 51  wherein said biocompatible polymer comprises a protein selected from the group consisting of gelatin, collagen, fibrinogen and fibronectin.  
     
     
         53 . The method of  claim 52  wherein said protein comprises gelatin.  
     
     
         54 . The method of  claim 53  wherein the average diameter of said particle is from about 40 to about 1200 microns.  
     
     
         55 . The method of  claim 54  wherein said particles, said liquid phase and said gaseous phase are combined at a ratio of from about 1:2:1 to about 1:12:13, based on g:ml:ml.  
     
     
         56 . The method of  claim 55  wherein the density of said substantially homogenous hemostatic composition is from about 0.9 g/ml to about 0.3 g/ml.  
     
     
         57 . The method of  claim 50  wherein said gas is selected from the group consisting of air, nitrogen, carbon dioxide, xenon and argon.  
     
     
         58 . The method of  claim 50  further comprising adding to said liquid phase a functionally effective amount of an additive selected from the group consisting of antimicrobial agents, foaming agents, foam stabilizers, surfactants, antioxidants, humectants, lubricants, thickeners, diluents, wetting agents, irradiation stabilizers, heparin neutralizers, procoagulants and hemostatic agents.  
     
     
         59 . The method of  claim 58  wherein up to about 20 weight percent of glycerol are added to said liquid, based on the weight of said liquid.  
     
     
         60 . The method of  claim 58  wherein up to about 1 weight percent of a quaternary amine is added to said liquid, based on the weight of said liquid.  
     
     
         61 . The method of  claim 50  further comprising irradiating said device having said substantially homogeneous composition dispensed therein with an amount of ionizing irradiation and for a time effective to provide a sterile device having a sterile, substantially homogeneous hemostatic composition disposed therein.  
     
     
         62 . The method of  claim 58  further comprising irradiating said device having said substantially homogeneous composition dispensed therein with an amount of ionizing irradiation and for a time effective to provide a sterile device having a sterile, substantially homogeneous hemostatic composition disposed therein.  
     
     
         63 . The method of  claim 62  wherein said additive is selected from the group consisting of fibrinogen and thrombin.