Highly efficacious hemostatic adhesive polymer scaffold

Abstract

The invention relates to biocompatible polymer gel compositions useful in facilitating and maintaining hemostasis. The biocompatible polymeric gel composition is comprised of (a) one or more than one polyanionic polymer, (b) one or more than one polycationic polymer, and (c) a solvent. A preferred composition includes sodium alginate, chitosan, and water to produce an adhesive hemostatic device that is useful in facilitating and maintaining rapid hemostasis.

What is claimed is: 
     
         1 . A polymeric composition comprising:
 a. about 0.1% to about 5% by weight of one or more than one polyanionic polymer;   b. about 5% to about 40% by weight of one or more than one polycationic polymer; and   c. about 50% to about 99.9% by weight solvent.   
     
     
         2 . A polymeric composition of  claim 1  wherein said one or more than one polyanionic polymer comprises sodium alginate, wherein said one or more than one polycationic polymer comprises chitosan, wherein said solvent is water. 
     
     
         3 . A polymeric composition of  claim 2  wherein the sodium alginate has a chain length of between about 1,000 nm and about 3,000 nm. 
     
     
         4 . A polymeric composition of  claim 2  wherein the sodium alginate has an average molecular weight of about 100 kDa to about 1,000 kDa. 
     
     
         5 . A polymeric composition of  claim 2  wherein the sodium alginate has an average molecular weight of about 500 kDa to about 900 kDa. 
     
     
         6 . A polymeric composition of  claim 2  wherein the sodium alginate has an average molecular weight of about 800 kDa. 
     
     
         7 . A polymeric composition of  claim 2  wherein the chitosan has a chain length of between about 2,000 nm and about 4,000 nm. 
     
     
         8 . A polymeric composition of  claim 2  wherein the chitosan has a chain length of between about 2,800 nm and about 2,900 nm. 
     
     
         9 . A polymeric composition of  claim 2  wherein the chitosan has a chain length of about 2,850 nm. 
     
     
         10 . A polymeric composition of  claim 2  wherein the chitosan has an average molecular weight of between about 1 kDa to about 2,000 kDa. 
     
     
         11 . A polymeric composition of  claim 2  wherein the chitosan has an average molecular weight of between about 1 kDa to about 1,000 kDa. 
     
     
         12 . A polymeric composition of  claim 2  wherein the chitosan has an average molecular weight of about 1,000 kDa. 
     
     
         13 . A polymeric composition of  claim 2  wherein the chitosan has an average degree of deacetylation of between about 75.0% to about 99.5%. 
     
     
         14 . A polymeric composition of  claim 2  wherein the chitosan is derived from an organic source. 
     
     
         15 . A polymeric composition of  claim 2  wherein the chitosan is derived from at least one of marine invertebrates and fungi. 
     
     
         16 . A polymeric composition of  claim 2  wherein the sodium alginate is derived from an organic source. 
     
     
         17 . A polymeric composition of  claim 2  wherein the sodium alginate is derived from marine algae. 
     
     
         18 . A polymeric composition of  claim 2  wherein the composition exhibits hemostatic efficacy in vitro in less than about 30 seconds upon introduction to blood. 
     
     
         19 . A polymeric composition of  claim 2  where in vitro hemostatic efficiency comprises an increase in clot strength units over a given time interval. 
     
     
         20 . A polymeric composition of  claim 19  where said hemostatic efficiency is measured by a coagulation analyzer. 
     
     
         21 . A polymeric composition of  claim 19  wherein clot strength units correspond to resistance of a clot to oscillation of a vertical probe against fibers of the clot. 
     
     
         22 . A polymeric composition of  claim 2  having a maximum clot strength from about 90 to about 200 clot strength units. 
     
     
         23 . A polymeric composition of  claim 2  wherein said composition withstands a vertical strain of up to about 0.5 Newtons per square millimeter without fracture. 
     
     
         24 . A polymeric composition of  claim 1  wherein one or more of the polycationic polymers is dispersed as solid phase particles in a solution of one or more of the polyanionic polymers. 
     
     
         25 . A polymeric composition of  claim 2  wherein the viscosity is from about 145,000 cP to about 250,000 cP at about 25° C. 
     
     
         26 . A polymeric composition of  claim 2  wherein the viscosity is about 169,500 cP at about 25° C. 
     
     
         27 . A polymeric composition of  claim 2  having a pH of about 7.0. 
     
     
         28 . A polymeric composition of  claim 2  having a Fourier Transform Infrared spectrum as depicted in  FIG. 3 . 
     
     
         29 . A polymeric composition of  claim 2  having a Fourier Transform Infrared spectrum comprising absorption peaks at: from about 3,600 cm −1  to about 3,000 cm −1 , about 2,900 cm −1 , about 1,640 cm −1 , and about 1,590 cm −1 . 
     
     
         30 . A polymeric composition of  claim 2  where said chitosan has an average degree of deacetylation of between about 75.0% to about 85.0%. 
     
     
         31 . A polymeric composition of  claim 2  where said chitosan has an average degree of deacetylation of between about 78.0% to about 83.0%. 
     
     
         32 . A polymeric composition of  claim 2  where said chitosan has an average degree of deacetylation of between about 80.0% to about 81.0%. 
     
     
         33 . A polymeric composition of  claim 2  where said chitosan has an average degree of deacetylation of about 80.5%. 
     
     
         34 . A polymeric composition of  claim 2  having a density of between about 1.10 g/mL and about 1.30 g/mL at about 25° C. 
     
     
         35 . A polymeric composition of  claim 2  having a density of about 1.21 g/mL at about 25° C. 
     
     
         36 . A polymeric composition of  claim 2  wherein about 13 mg or more of said composition coagulates about 0.34 mL of blood in vitro. 
     
     
         37 . A polymeric composition of  claim 2  having a modulus of elasticity of between about 6 kPa and about 23 kPa. 
     
     
         38 . A polymeric composition of  claim 37  wherein the modulus of elasticity is about 16 kPa. 
     
     
         39 . A polymeric composition of  claim 2  comprising:
 a. about 2.5% by weight of sodium alginate; 
 b. about 8% by weight of chitosan; and 
 c. about 89.5% by weight water. 
 
     
     
         40 . A method of making a polymeric composition comprising:
 a. mixing sodium alginate with water at a first speed to make a first mixture having a first viscosity, and then   b. adding chitosan to said first mixture and mixing at a second speed to make a second mixture having a second viscosity.   
     
     
         41 . A method of  claim 40  wherein the first viscosity is between about 500 cP to about 2,000 cP at about 25° C. 
     
     
         42 . A method of  claim 40  wherein said sodium alginate comprises particles having an average particle size of between 10 mesh and 300 mesh. 
     
     
         43 . A method of  claim 40  wherein the chitosan has a viscosity of between about 100 cP to about 1,000 cP in a 1% w/v solution in 5% acetic acid at about 25° C. 
     
     
         44 . A method of  claim 40  wherein said second viscosity is about 169,500 cP at about 25° C. 
     
     
         45 . A method of  claim 40  wherein the chitosan comprises particles having an average particle size of between 50 mesh to 500 mesh. 
     
     
         46 . A method of  claim 40  where said mixing sodium alginate with water at a first speed is performed for about six hours. 
     
     
         47 . A method of  claim 40  where said mixing at a second speed is performed for about one hour. 
     
     
         48 . A method of  claim 40  where said second speed is faster than said first speed. 
     
     
         49 . A method of  claim 40  wherein the sodium alginate has a morphology of at least one of: fibrous, crystalline, amorphous, spherical, and cuboidal. 
     
     
         50 . A method of  claim 40  wherein the chitosan has a morphology of at least one of: fibrous, crystalline, amorphous, spherical, and cuboidal. 
     
     
         51 . A method of  claim 40  wherein the chitosan has a spherical morphology. 
     
     
         52 . A polymeric composition made by the method of  claim 40 . 
     
     
         53 . A polymeric composition made by the method of  claim 40  having (a) between about 0.0200 g/mL and about 0.0230 g/mL sodium alginate and (b) between about 0.185 g/mL and about 0.210 g/mL chitosan. 
     
     
         54 . A polymeric composition made by the method of  claim 40  having a Fourier Transform Infrared spectrum as depicted in  FIG. 3 . 
     
     
         55 . A polymeric composition made by the method of  claim 40  wherein the sodium alginate has a Fourier Transform Infrared spectrum comprising absorption peaks at: from about 3,600 cm −1  to about 3,000 cm −1 , about 2,900 cm −1 , about 1,600 cm −1 , and about 1,400 cm −1 . 
     
     
         56 . A polymeric composition made by the method of  claim 40  wherein the sodium alginate has a Fourier Transform Infrared spectrum as depicted in  FIG. 1 . 
     
     
         57 . A polymeric composition made by the method of  claim 40  wherein the chitosan has a Fourier Transform Infrared spectrum comprising absorption peaks at: from about 3,600 cm −1  to about 3,000 cm −1 , about 2,910 cm −1 , about 2,870 cm −1 , about 1,650 cm −1 , and about 1,580 cm −1 . 
     
     
         58 . A polymeric composition made by the method of  claim 40  wherein the chitosan has a Fourier Transform Infrared spectrum as depicted in  FIG. 2 . 
     
     
         59 . A polymeric composition made by the method of  claim 40  having a pH of about 7.0. 
     
     
         60 . A method of  claim 40  where said chitosan has an average degree of deacetylation of between about 75.0% to about 99.5%. 
     
     
         61 . A method of  claim 40  where said chitosan has an average degree of deacetylation of between about 75.0% to about 85.0%. 
     
     
         62 . A method of  claim 40  where said chitosan has an average degree of deacetylation of between about 78.0% to about 83.0%. 
     
     
         63 . A method of  claim 40  where said chitosan has an average degree of deacetylation of between about 80.0% to about 81.0%. 
     
     
         64 . A method of  claim 40  where said chitosan has an average degree of deacetylation of about 80.5%. 
     
     
         65 . A polymeric composition made by the method of  claim 40  having a density of between about 1.10 g/mL and 1.30 g/mL at about 25° C. 
     
     
         66 . A polymeric composition made by the method of  claim 40  having a density of about 1.21 g/mL at about 25° C. 
     
     
         67 . A method of  claim 40  wherein said sodium alginate comprises particles having an average particle size of about 180 mesh. 
     
     
         68 . A method of  claim 40  wherein the chitosan comprises particles having an average particle size of about 100 mesh. 
     
     
         69 . A sterile polymeric composition having a viscosity between about 165,000 cP and about 174,000 cP at about 25° C. comprising:
 (a) alginate; and 
 (b) chitosan having an average degree of deacetylation of between about 75.0% and about 99.5%. 
 
     
     
         70 . A sterile polymeric composition of  claim 69  having a viscosity of about 169,500 cP at about 25° C. 
     
     
         71 . A sterile polymeric composition of  claim 69  where said chitosan has an average degree of deacetylation of between about 75.0% to about 99.5%. 
     
     
         72 . A sterile polymeric composition of  claim 69  where said chitosan has an average degree of deacetylation of between about 75.0% to about 85.0%. 
     
     
         73 . A sterile polymeric composition of  claim 69  said chitosan has an average degree of deacetylation of between about 78.0% to about 83.0%. 
     
     
         74 . A sterile polymeric composition of  claim 69  where said chitosan has an average degree of deacetylation of between about 80.0% to about 81.0%. 
     
     
         75 . A sterile polymeric composition of  claim 69  where said chitosan has an average degree of deacetylation of about 80.5%. 
     
     
         76 . A sterile polymeric composition of  claim 70  where said chitosan has an average degree of deacetylation of about 80.5%. 
     
     
         77 . A sterile polymeric composition of  claim 69  having a density of between about 1.10 g/mL and 1.30 g/mL at about 25° C. 
     
     
         78 . A sterile polymeric composition of  claim 69  having a density of about 1.21 g/mL at about 25° C. 
     
     
         79 . A sterile polymeric composition of  claim 69  having a pH of about 7.0. 
     
     
         80 . A polymeric composition having a Fourier Transform Infrared spectrum as depicted in  FIG. 3 . 
     
     
         81 . A polymeric composition comprising sodium alginate and chitosan having a Fourier Transform Infrared spectrum comprising absorption peaks at: from about 3,600 cm −1  to about 3,000 cm −1 , about 2,900 cm −1 , about 1,640 cm −1 , and about 1,590 cm −1 . 
     
     
         82 . A kit comprising a first container having a polymeric composition of  claim 2 . 
     
     
         83 . A kit of  claim 82  comprising a second container having a calcium chloride solution. 
     
     
         84 . A kit of  claim 83  where said calcium chloride solution is a 10% w/v calcium chloride solution in water. 
     
     
         85 . A polymeric composition comprising:
 a. alginate having a chain length of between about 1,000 nm and about 3,000 nm and an average molecular weight of about 800 kDa; and   b. chitosan having a chain length of between about 2,800 nm and about 2,900 nm and an average molecular weight of about 1,000 kDa.   
     
     
         86 . A polymeric composition of  claim 2  wherein the chitosan is derived from a plant. 
     
     
         87 . A polymeric composition of  claim 2  wherein the chitosan is derived from algae. 
     
     
         88 . A polymeric composition made by the method of  claim 40  having (a) about 0.0225 g/mL sodium alginate and (b) about 0.200 g/mL chitosan. 
     
     
         89 . A polymeric composition made by the method of  claim 40  having (a) about 0.021 g/mL sodium alginate and (b) about 0.190 g/mL chitosan. 
     
     
         90 . A polymeric composition made by the method of  claim 40  having (a) about 0.02247 g/mL sodium alginate and (b) about 0.200 g/mL chitosan. 
     
     
         91 . A polymeric composition made by the method of  claim 40  having (a) about 0.0212 g/mL sodium alginate and (b) about 0.1887 g/mL chitosan. 
     
     
         92 . A polymeric composition of  claim 2  wherein the chitosan is bound to a core comprising a polymeric material. 
     
     
         93 . A polymeric composition of  claim 2  wherein the is bound to a core comprising poly-L-lactic acid. 
     
     
         94 . A polymeric composition of  claim 1  wherein said one or more than one polyanionic polymer comprises sodium alginate, wherein said one or more than one polycationic polymer comprises diethylaminoethyl-dextran bound to a core of poly-L-lactic acid, and wherein said solvent is water. 
     
     
         95 . A polymeric composition of  claim 2  further comprising methylparaben.