Polyphosphate-functionalized inorganic nanoparticles as hemostatic compositions and methods of use
A hemostatic composition is provided. The hemostatic composition includes a hemostatically effective amount of a hemostatic agent that includes a nanoparticle and a polyphosphate polymer attached to the nanoparticle. Also provided are medical devices and methods of use to promote blood clotting.
1. A hemostatic composition comprising a hemostatically effective amount of a hemostatic agent comprising:
a silica nanoparticle; and
a polyphosphate polymer attached to the silica nanoparticle.
2. The hemostatic composition of claim 1 , wherein the polyphosphate polymer comprises 20 to 1500 phosphate monomers.
3. The hemostatic composition of claim 2 , wherein the polyphosphate polymer comprises 70 to 1500 phosphate monomers.
4. The hemostatic composition of claim 1 , wherein the hemostatic agent has a polyphosphate polymer to silica nanoparticle mass ratio of 1:2 to 1:5.
5. The hemostatic composition of claim 1 , wherein the hemostatic agent has a polyphosphate polymer to silica nanoparticle mass ratio of 1:1 to 1:5.
6. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 100 nm or less.
7. The hemostatic composition of claim 1 , wherein the hemostatic agent further comprises a protecting agent attached to the hemostatic agent by an enzymatically-cleavable linking group.
8. The hemostatic composition of claim 7 , wherein the protecting agent comprises a polyethylene glycol polymer.
9. The hemostatic composition of claim 8 , wherein the polyethylene glycol polymer has a molecular mass of 1000 Da or more.
10. A method of promoting blood clotting at a hemorrhage site, comprising:
administering to a hemorrhage site in a subject in need thereof, the hemostatic composition of claim 1 for a period of time sufficient to at least initiate blood clotting at the hemorrhage site.
11. The method of claim 10 , wherein the hemorrhage site is an external hemorrhage site.
12. The method of claim 11 , wherein the administering comprises applying the hemostatic composition to the external hemorrhage site.
13. The method of claim 10 , wherein the hemorrhage site is an internal hemorrhage site, and wherein the hemostatic
agent further comprises a protecting agent attached to the hemostatic agent by an enzymatically-cleavable linking group.
14. The method of claim 13 , wherein the administering comprises intravenously administering the hemostatic composition to the subject.
15. The hemostatic composition of claim 1 , wherein the polyphosphate polymer comprises 10 to 200 phosphate monomers.
16. The hemostatic composition of claim 1 , wherein the polyphosphate polymer comprises 200 to 1300 phosphate monomers.
17. The hemostatic composition of claim 1 , wherein the hemostatic agent has a polyphosphate polymer to silica nanoparticle mass ratio of 1:1.
18. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 150 nm or less.
19. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 200 nm or less.
20. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 200 nm or less.
21. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 250 nm or less.
22. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 500 nm or less.
23. The hemostatic composition of claim 1 , wherein the silica nanoparticle has an average diameter of 750 nm or less.
24. A medical device comprising:
a hemostatic composition comprising: a silica nanoparticle; and
a polyphosphate polymer attached to the silica nanoparticle; and a sterile substrate on which the hemostatic composition is disposed.
25. The device of claim 24 , wherein the substrate is adapted for delivery of the hemostatic composition to a bleeding wound.
26. The device of claim 25 , wherein the substrate is a bandage, gauze, or sponge.
27. The device of claim 24 , further comprising a sealed package containing the hemostatic composition.