Flowable collagen-based hemostat and methods of use

Abstract

The invention relates to methods for fabricating a flowable hemostatic composition. The invention also relates to hemostatic compositions and methods for promoting wound healing. In various embodiments, the hemostatic compositions comprise crosslinkable collagen molecules having a porosity controlled by the ratio of weight percent collagen solids to weight percent crosslinker when crosslinking the collagen. In other embodiments, the hemostatic compositions comprise crosslinkable collagen molecules having a porosity controlled by the temperature and rate of freezing when drying the composition during fabrication. In some embodiments, the compositions contain additional agents, including biological agents.

1 - 30 . (canceled) 
     
     
         31 . A flowable hemostatic composition comprising:
 crosslinked collagen having a porosity greater than 50% and a surface area of between 0.5 to 30 m 2 /g; and   a physiologically acceptable liquid vehicle selected from the group consisting of water, saline, calcium chloride, and combinations thereof,   wherein the porosity of the composition is controlled by temperature and rate of freezing during lyophilization.   
     
     
         32 . The composition of  claim 31 , wherein the crosslinked collagen comprises at least one material from the group consisting of fibers, ribbons, ropes, and sheets. 
     
     
         33 . The composition of  claim 31 , wherein the porosity is further controlled by the ratio of percent collagen solids to percent crosslinker when crosslinking the collagen. 
     
     
         34 . The composition of  claim 31 , wherein the crosslinked collagen is fibrillar collagen. 
     
     
         35 . The composition of  claim 31 , further comprising adding at least one biological agent. 
     
     
         36 . The composition of  claim 31 , further comprising controlling the porosity by controlling the collagen concentration prior to freezing the collagen. 
     
     
         37 . The composition of  claim 31 , wherein the controlled temperature rate of freezing comprises a freezing time of 2 to 6 hours, a primary drying cycle, and a secondary drying cycle. 
     
     
         38 . The composition of  claim 37 , wherein the primary drying cycle is performed at temperatures between 0 and 15° C. for 1 to 24 hours and the secondary drying cycle is performed at temperatures between 20 and 40° C. for 2 to 10 hours 
     
     
         39 . The composition of  claim 31 , wherein the composition can be dispensed from a syringe having at least a 1.6 mm opening. 
     
     
         40 . The composition of  claim 31 , wherein the composition does not include thrombin. 
     
     
         41 . The composition of  claim 31 , wherein the composition has a percent swelling of between 0% and 20% within 10 minutes. 
     
     
         42 . A method of fabricating a flowable hemostatic composition comprising:
 crosslinking collagen with a crosslinking agent to form crosslinked collagen, wherein the crosslinked collagen has a porosity greater than 50% and a surface area between 0.5 to 30 30 m2/g;   lyophilizing the crosslinked collagen; and   reconstituting the crosslinked collagen with a physiologically acceptable liquid vehicle selected from the group consisting of water, saline, calcium chloride, and combinations thereof.   
     
     
         43 . The method of  claim 42 , the crosslinking agent is glutaraldehyde. 
     
     
         44 . The method of  claim 42 , wherein the collagen is microfibrillar collagen. 
     
     
         45 . The method of  claim 42 , wherein the collagen is fibrillar collagen. 
     
     
         46 . The method of  claim 42 , further comprising controlling the porosity of the crosslinked collagen by controlling the temperature and rate of freezing during lyophilization. 
     
     
         47 . The method of  claim 42 , further comprising controlling the porosity by controlling the collagen concentration prior to freezing the collagen. 
     
     
         48 . The method of  claim 42 , further comprising controlling the material structure of the crosslinked collagen by controlling the temperature and rate of freezing during lyophilization. 
     
     
         49 . The method of  claim 48 , wherein the controlled temperature rate of freezing comprises a freezing time of 2 to 6 hours, a primary drying cycle, and a secondary drying cycle. 
     
     
         50 . The method of  claim 49 , wherein the primary drying cycle is performed at temperatures between 0 and 15° C. for 1 to 24 hours and the secondary drying cycle is performed at temperatures between 20 and 40° C. for 2 to 10 hours