Inorganic materials for hemostatic modulation and therapeutic wound healing

Abstract

The invention provides compositions, methods and devices relating to a silaceous oxide that generates a reduced heat of hydration upon contact with blood. By reducing the heat of hydration, the compositions provide a hemostatic agent that attenuates a tissue burning side effect of conventional hemostatic agents without adversely affecting the wound healing properties of the composition.

1 - 28 . (canceled) 
   
   
       29 . A hemostatic composition for treating a bleeding wound comprising a hemostatically effective amount of a bioactive glass, wherein the bioactive glass has a ratio of Si to Ca ranging from 0.2 to 6, and wherein the bioactive glass has an average particle size ranging from 10 nm to 100 μm. 
   
   
       30 . The composition of  claim 29 , wherein the bioactive glass has a ratio of Si to Ca of 2.5. 
   
   
       31 . The composition of  claim 29 , wherein the bioactive glass has an average particle size ranging from 50 nm to 200 nm. 
   
   
       32 . The composition of  claim 31 , wherein the bioactive glass has an average particle size ranging from 10 nm to 50 nm. 
   
   
       33 . The composition of  claim 31 , wherein the bioactive glass comprises porous bioactive glass. 
   
   
       34 . The composition of  claim 33 , wherein the bioactive glass has pores that have an average diameter ranging from 2 nm to 100 nm. 
   
   
       35 . The composition of  claim 34 , wherein the bioactive glass has pores that have an average diameter ranging from 2 nm to 50 nm. 
   
   
       36 . The composition of  claim 29 , wherein the bioactive glass has an internal surface area ranging from 1 m 2 /g to 1500 m 2 /g as determined by BET N 2  adsorption. 
   
   
       37 . The composition of  claim 36 , wherein the bioactive glass has an internal surface area ranging from 100 m 2 /g to 500 m 2 /g as determined by BET N 2  adsorption. 
   
   
       38 . The composition of  claim 29 , wherein the bioactive glass comprises non-porous bioactive glass. 
   
   
       39 . The composition of  claim 29 , wherein the bioactive glass comprises spherical bioactive glass. 
   
   
       40 . The composition of  claim 29 , wherein the bioactive glass is produced by sol-gel synthesis. 
   
   
       41 . The composition of  claim 29 , further comprising a biologically active agent attached on a surface of the bioactive glass, wherein the biologically active agent is a clot promoting reactant. 
   
   
       42 . The composition of  claim 41 , wherein the clot promoting reactant comprises thrombin. 
   
   
       43 . A medical device comprising a coating comprising the composition of  claim 29 . 
   
   
       44 . A method of modulating hemostasis comprising contacting a bleeding wound with a hemostatically effective amount of a bioactive glass. 
   
   
       45 . The method of  claim 44 , wherein the modulating comprises decreasing blood coagulation time. 
   
   
       46 . The method of  claim 44 , wherein the bioactive glass has a ratio of Si to Ca ranging from 0.2 to 6, and wherein the bioactive glass has an average particle size ranging from 10 nm to 100 μm. 
   
   
       47 . The method of  claim 46 , wherein the bioactive glass has a ratio of Si to Ca of 2.5. 
   
   
       48 . The method of  claim 46 , wherein the bioactive glass has an average particle size ranging from 50 nm to 200 nm. 
   
   
       49 . The method of  claim 46 , wherein the bioactive glass has an average particle size ranging from 10 nm to 50 nm. 
   
   
       50 . The method of  claim 44 , wherein the bioactive glass comprises porous bioactive glass. 
   
   
       51 . The method of  claim 50 , wherein the bioactive glass has pores that have an average diameter ranging from 2 nm to 100 nm. 
   
   
       52 . The method of  claim 51 , wherein the bioactive glass has pores that have an average diameter ranging from 2 nm to 50 nm. 
   
   
       53 . The method of  claim 44 , wherein the contacting results in a time to initiate clot formation (R), as measured by thromboelastography, of 3 minutes or less. 
   
   
       54 . The method of  claim 44 , wherein the contacting results in a maximum clot strength (MA), as measured by thromboelastography, of 70 dyn/cm 2  or greater. 
   
   
       55 . The method of  claim 44 , wherein the modulating comprises increasing the rate of coagulation. 
   
   
       56 . The method of  claim 54 , wherein the contacting results in a rate of coagulation (α), as measured by thromboelastography, of 75° or greater. 
   
   
       57 . A method of making a hemostatic bioactive glass composition comprising:
 mixing one or more inorganic precursors with a solution to produce a sol-gel solution; and   drying the sol-gel solution to produce the hemostatic bioactive glass composition.   
   
   
       58 . The method of  claim 57 , wherein the solution comprises a polymer, and wherein the hemostatic bioactive glass composition comprises porous bioactive glass. 
   
   
       59 . The method of  claim 58 , wherein the polymer is a poly(ethyleneoxide)-poly(propylene oxide)-poly(ethylene oxide) copolymer. 
   
   
       60 . The method of  claim 57 , further comprising calcining the hemostatic bioactive glass composition. 
   
   
       61 . The method of  claim 57 , wherein the drying comprises spraying the sol-gel solution into a furnace, and wherein the hemostatic bioactive glass composition comprises spherical bioactive glass. 
   
   
       62 . The method of  claim 57 , wherein the one of more inorganic precursors comprise tetraethyl orthosilicate, Ca(NO 3 ) 2 , and triethyl phosphate. 
   
   
       63 . The method of  claim 57 , further comprising attaching a clot promoting reactant to the hemostatic bioactive glass composition. 
   
   
       64 . The method of  claim 63 , wherein the clot promoting reactant comprises thrombin. 
   
   
       65 . The method of  claim 57 , wherein the hemostatic bioactive glass composition comprises non-porous bioactive glass. 
   
   
       66 . A hemostatic bioactive glass composition produced by the method of  claim 57 . 
   
   
       67 . The composition of  claim 66 , wherein the hemostatic bioactive glass composition has an average particle size ranging from 10 nm to 100 μm. 
   
   
       68 . The composition of  claim 67 , wherein the hemostatic bioactive glass composition has an average particle size ranging from 50 nm to 200 nm. 
   
   
       69 . The composition of  claim 67 , wherein the hemostatic bioactive glass composition has an average particle size ranging from 10 nm to 50 nm. 
   
   
       70 . The composition of  claim 66 , wherein the method further comprises attaching a clot promoting reactant to the hemostatic bioactive glass composition. 
   
   
       71 . The composition of  claim 70 , wherein the clot promoting reactant comprises thrombin. 
   
   
       72 . A hemostatic composition for treating a bleeding wound comprising a hemostatically effective amount of a bioactive glass and a biologically active agent attached on a surface of the bioactive glass. 
   
   
       73 . The composition of  claim 72 , wherein the biologically active agent is a clot promoting reactant. 
   
   
       74 . The composition of  claim 73 , wherein the clot promoting reactant comprises thrombin.