Hemostatic sponge
The present invention provides a hemostatic porous composite sponge comprising i) a matrix of a biomaterial and ii) one hydrophilic polymeric component comprising reactive groups wherein i) and ii) are associated with each other so that the reactivity of the polymeric component is retained, wherein associated means that said polymeric component is coated onto a surface of said matrix of a biomaterial, or said matrix is impregnated with said polymeric material, or both.
1. A hemostatic porous composite sponge, comprising:
a matrix of a biomaterial; and
a single hydrophilic polymeric crosslinker comprising reactive groups,
wherein the matrix and the single hydrophilic polymeric crosslinker are associated with each other so that:
the reactivity of the hydrophilic polymeric crosslinker is retained, and
the single hydrophilic polymeric crosslinker is coated onto a surface of the matrix, or the matrix is impregnated with the single hydrophilic polymeric crosslinker, or both.
2. The hemostatic porous composite sponge claim 1 , wherein the biomaterial is selected from the group consisting of collagen, gelatin, fibrin, a polysaccharide, a synthetic biodegradable biomaterial, and derivatives thereof.
3. The hemostatic porous composite sponge of claim 2 , wherein the polysaccharide comprises chitosan.
4. The hemostatic porous composite sponge of claim 2 , wherein the synthetic biodegradable biomaterial comprises polylactic acid or polyglycolic acid.
5. The hemostatic porous composite sponge of claim 1 , wherein the hydrophilic polymeric crosslinker comprises a polyalkylene oxide polymer.
6. The hemostatic porous composite sponge of claim 5 , wherein the polyalkylene oxide polymer comprises polyethylene glycol (PEG).
7. The hemostatic porous composite sponge of claim 5 , wherein the polyalkylene oxide polymer comprises a multi-electrophilic polyalkylene oxide polymer.
8. The hemostatic porous composite sponge of claim 5 , wherein the polyalkylene oxide polymer comprises a multi-electrophilic polyethylene glycol (PEG).
9. The hemostatic porous composite sponge of claim 5 , wherein the polyalkylene oxide polymer comprises pentaerythritolpoly(ethyleneglycol)ether tetrasuccinimidyl glutarate.
10. The hemostatic porous composite sponge of claim 1 , wherein the biomaterial is collagen, wherein the polymeric crosslinker is pentaerythritolpoly(ethyleneglycol)ether tetrasuccinimidyl glutarate, and wherein the polymeric crosslinker is coated onto the collagen.
11. The hemostatic porous composite sponge of claim 1 , wherein the biomaterial is collagen, wherein the polymeric component is pentaerythritolpoly(ethyleneglycol)ether tetrasuccinimidyl glutarate, and wherein the polymeric component is impregnated into the collagen.
12. The hemostatic porous composite sponge of claim 1 , wherein the sponge material has a pore size of about 5 to about 500 μm.
13. The hemostatic porous composite sponge of claim 1 , wherein the sponge comprises about 5 to about 100 mg collagen/cm 3 of the sponge.
14. The hemostatic porous composite sponge of claim 1 , wherein the polymeric crosslinker is coated onto a surface of the matrix of biomaterial as a discontinuous layer.
15. The hemostatic porous composite sponge of claim 1 , wherein the sponge comprises from about 1 to about 20 mg polymeric crosslinker/cm 2 of the sponge.
16. The hemostatic porous composite sponge of claim 1 , further comprising a dye coated on at least a portion of the matrix.
17. The hemostatic porous composite sponge of claim 1 , further comprising at least one physiologic substance selected from the group consisting of antifibrinolytics, antibiotics, antibacterials, antimycotics, growth factors, pain killers, enzymes, and enzyme inhibitors.
18. The hemostatic porous composite sponge of claim 17 , wherein the physiologic substance comprises an antifibrinolytic selected from the group consisting of aprotinin, an aprotinin derivative, alpha2-macroglobulin, an inihibitor of protein C, an inactivator of protein C, an inhibitor of activated protein C, an inactivator of activated protein C, a substrate mimic binding to plasmin that acts competitively with natural substrates, and an antibody inhibiting fibrinolytic activity.
19. The hemostatic porous composite sponge of claim 1 , wherein the sponge has a water content of below about 2% w/w.
20. The hemostatic porous composite sponge of claim 1 , wherein the sponge includes a layer of a further biomaterial comprising oxidized cellulose.
21. The hemostatic porous composite sponge of claim 1 , wherein the sponge comprises a biological decomposition in vivo of less than 6 months.
22. The hemostatic porous composite sponge of claim 1 , wherein the sponge comprises a thrombin activity or thrombin equivalent activity of between about 100 and about 10,000.
23. A method of treating an injury, comprising:
administering a hemostatic porous composite sponge to the injury, the sponge comprising:
a matrix of a biomaterial; and
a single hydrophilic polymeric crosslinker comprising reactive groups,
wherein the matrix and the single hydrophilic polymeric crosslinker are associated with each other so that:
the reactivity of the single hydrophilic polymeric crosslinker is retained, and
the single hydrophilic polymeric crosslinker is coated onto a surface of the matrix, or the matrix is impregnated with the single hydrophilic polymeric crosslinker, or both, and
wherein the injury comprises a member selected from the group consisting of a wound, a hemorrhage, a damaged tissue, and a bleeding tissue.
24. The method of claim 23 , wherein the sponge is applied to the injury together with a buffer solution.
25. The method of claim 24 , wherein the buffer solution comprises a bicarbonate solution.
26. The method of claim 24 , wherein the buffer solution is present on a gauze.
27. A kit, comprising:
a hemostatic porous composite sponge, comprising:
a matrix of a biomaterial; and
a single hydrophilic polymeric crosslinker comprising reactive groups,
wherein the matrix and the single hydrophilic polymeric crosslinker are associated with each other so that:
the reactivity of the single hydrophilic polymeric crosslinker is retained, and
the single hydrophilic polymeric crosslinker is coated onto a surface of the matrix, or the matrix is impregnated with the single hydrophilic polymeric crosslinker, or both;
a buffer solution; and
instructions for using the hemostatic porous composite sponge and the buffer solution.
28. The kit of claim 27 , wherein the buffer solution comprises an alkaline buffer solution.
29. The kit of claim 28 , wherein the alkaline buffer solution comprises a bicarbonate.
30. A hemostatic composite, comprising:
a haemostatic material; and
a single hydrophilic polymeric crosslinker with reactive groups associated with the haemostatic material such that the reactivity of the single hydrophilic polymeric crosslinker is retained,
wherein the composite comprises pore which allow external fluids to access into the composite.
31. The hemostatic composite of claim 30 , wherein the pores allow human blood to access into the composite.
32. The hemostatic composite of claim 30 , wherein the haemostatic material is a non-woven or a woven fabric of a haemostatic fiber or a porous haemostatic sponge.
33. The hemostatic composite of claim 30 , wherein the haemostatic material is a collagen sponge, a fabric of oxidized cellulose, a fibrin sponge, or a gelatin sponge.
34. The hemostatic composite of claim 30 , wherein the hydrophilic polymeric crosslinker with reactive groups is a polyethylene glycol (PEG).
35. The hemostatic composite of claim 30 , wherein the hydrophilic polymeric crosslinker comprises a polyethylene glycol (PEG) comprising two or more reactive groups selected from the group consisting of succinimidylesters (—CON(COCH 2 ) 2 ), aldehydes (—CHO), and isocyanates (—N═C═O).
36. The hemostatic composite of claim 30 , wherein the hydrophilic polymeric crosslinker comprises a polyethylene glycol (PEG) comprising succinimidylester reactive groups.