Polyphosphate-Functionalized Inorganic Nanoparticles as Hemostatic Compositions and Methods of Use

1 . A hemostatic composition comprising a hemostatically effective amount of a hemostatic agent comprising:

a nanoparticle; and

a polyphosphate polymer attached to the nanoparticle.

2 . The hemostatic composition of claim 1 , wherein the polyphosphate polymer comprises 20 or more phosphate monomers.

3 . The hemostatic composition of claim 2 , wherein the polyphosphate polymer comprises 70 or more phosphate monomers.

4 . The hemostatic composition of claim 1 , wherein the hemostatic agent has a polyphosphate polymer to nanoparticle mass ratio of 1:2 or more.

5 . The hemostatic composition of claim 1 , wherein the hemostatic agent has a polyphosphate polymer to nanoparticle mass ratio of 1:1 or more.

6 . The hemostatic composition of claim 1 , wherein the nanoparticle comprises a material selected from the group consisting of iron oxide, diatomaceous earth, an aluminosilicate, an oxide of a transition metal, titanium dioxide, and calcium hydroxyapatite.

7 . (canceled)

8 . The hemostatic composition of claim 7 , wherein the nanoparticle has an average diameter of 100 nm or less.

9 . 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.

10 . The hemostatic composition of claim 9 , wherein the protecting agent comprises a polyethylene glycol polymer.

11 . The hemostatic composition of claim 10 , wherein the polyethylene glycol polymer has a molecular mass of 1000 Da or more.

12 . A medical device comprising:

a hemostatic composition comprising:

a nanoparticle; and

a polyphosphate polymer attached to the nanoparticle; and

a sterile substrate on which the hemostatic composition is disposed.

13 . The device of claim 12 , wherein the substrate is adapted for delivery of the hemostatic composition to a bleeding wound.

14 . The device of claim 13 , wherein the substrate is a bandage, gauze, or sponge.

15 . The device of claim 12 , further comprising a sealed package containing the hemostatic composition.

16 . A method of promoting blood clotting at a hemorrhage site, comprising:

administering to a hemorrhage site in a subject the hemostatic composition of claim 1 for a period of time sufficient to at least initiate blood clotting at the hemorrhage site.

17 . The method of claim 16 , wherein the hemorrhage site is an external hemorrhage site.

18 . The method of claim 17 , wherein the administering comprises applying the hemostatic composition to the external hemorrhage site.

19 . The method of claim 16 , wherein the hemorrhage site is an internal hemorrhage site, and the hemostatic composition is a hemostatic composition of claim 9 .

20 . The method of claim 19 , wherein the administering comprises intravenously administering the hemostatic composition to the subject.

21 . The hemostatic composition of claim 1 , wherein the nanoparticle is an inorganic nanoparticle.

22 . The hemostatic composition of claim 1 , wherein the nanoparticle is an organic nanoparticle.

23 . The hemostatic composition of claim 1 , wherein the polyphosphate polymer comprises 10 to 200 phosphate monomers.

24 . The hemostatic composition of claim 1 , wherein the polyphosphate polymer comprises 200 to 1300 phosphate monomers.

25 . The hemostatic composition of claim 1 , wherein the nanoparticle has an average diameter of 150 nm or less.

26 . The hemostatic composition of claim 1 , wherein the nanoparticle has an average diameter of 200 nm or less.

27 . The hemostatic composition of claim 1 , wherein the nanoparticle has an average diameter of 250 nm or less.

28 . The hemostatic composition of claim 1 , wherein the nanoparticle has an average diameter of 500 nm or less.

29 . The hemostatic composition of claim 1 , wherein the nanoparticle has an average diameter of 750 nm or less.