Antithrombotic nanoparticle

Patent metadata

Field	Value
Publication number	US-9764043-B2
Application number	US-201013516528-A
Country	US
Kind code	B2
Filing date	Dec 17, 2010
Priority date	Dec 17, 2009
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

The present invention encompasses an antithrombotic nanoparticle.

First claim

What is claimed is:

1. An antithrombotic nanoparticle comprising a core and an outer layer, wherein the core comprises a perfluorocarbon that is a liquid at about 37° C. and the outer layer comprises a mixture of a lipid and a surfactant; and wherein the exterior of the nanoparticle comprises a direct thrombin inhibitor covalently conjugated to the exterior via the lipid component of the nanoparticle's outer layer, such that the nanoparticle has a second order kinetic constant for the direct thrombin inhibitor-thrombin interaction that is greater than the same kinetic constant of the direct thrombin inhibitor by itself, and wherein the nanoparticle is antithrombotic but does not substantially alter the clotting time of a subject's blood plasma.

2. The antithrombotic nanoparticle of claim 1 , wherein the nanoparticle further comprises an anti-platelet agent.

3. The antithrombotic nanoparticle of claim 1 , wherein the direct thrombin inhibitor is bivalirudin.

4. The antithrombotic nanoparticle of claim 1 , wherein the direct thrombin inhibitor is D-phenylalyl-L-prolyl-L-arginyl-chloromethyl ketone (PPACK).

5. A composition, the composition comprising:
a. a plurality of platelets,
b. fibrin, and
c. at least one nanoparticle comprising a core and an outer layer, wherein the core comprises a perfluorocarbon that is a liquid at about 37° C. and the outer layer comprises a mixture of a lipid and a surfactant; and wherein the exterior of the nanoparticle comprises a direct thrombin inhibitor covalently conjugated to the exterior via the lipid component of the nanoparticle's outer layer, such that the nanoparticle has a second order kinetic constant for the direct thrombin inhibitor-thrombin interaction that is greater than the same kinetic constant of the direct thrombin inhibitor by itself, and wherein the nanoparticle is antithrombotic but does not substantially alter the clotting time of a subject's blood plasma.

6. A method of decreasing, preventing, or imaging thrombus formation in a subject, the method comprising administering to the subject a nanoparticle comprising a core and an outer layer, wherein the core comprises a perfluorocarbon that is a liquid at about 37° C. and the outer layer comprises mixture of a lipid and a surfactant; and wherein the exterior of the nanoparticle comprises a direct thrombin inhibitor covalently conjugated to the exterior via the lipid component of the nanoparticle's outer layer, such that the nanoparticle has a second order kinetic constant for the direct thrombin inhibitor-thrombin interaction that is greater than the same kinetic constant of the direct thrombin inhibitor by itself, and wherein the nanoparticle is antithrombotic but does not substantially alter the clotting time of a subject's blood plasma.

7. The method of claim 6 , wherein the nanoparticle further comprises an anti-platelet agent.

8. The method of claim 6 , wherein the direct thrombin inhibitor is bivalirudin.

9. The method of claim 6 , wherein the direct thrombin inhibitor is D-phenylalyl-L-prolyl-L-arginyl-chloromethyl ketone (PPACK).

10. The nanoparticle of claim 1 , wherein the direct thrombin inhibitor is conjugated to the lipid component of the nanoparticle's coat via a linking molecule.

11. The nanoparticle of claim 1 , wherein the direct thrombin inhibitor is directly conjugated to the lipid component of the nanoparticle's coat.

12. The method of claim 6 , wherein the direct thrombin inhibitor is conjugated to the lipid component of the nanoparticle's coat via a linking molecule.

13. The method of claim 6 , wherein the direct thrombin inhibitor is directly conjugated to the lipid component of the nanoparticle's coat.

Assignees

• Myerson Jacob
• Wickline Samuel A
• Univ Washington

Inventors

• Myerson Jacob
• Wickline Samuel A

Classifications

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61K47/6909

  Micelles formed by phospholipids · CPC title

• A61K47/64 Primary

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K47/544

  Phospholipids · CPC title

• A61K47/48215

  Human Necessities · mapped topic