US 9,808,500 B2
Antithrombotic nanoparticle
Samuel A. Wickline, St. Louis, MO (US); Jacob Myerson, St. Louis, MO (US); Rohun Palekar, St. Louis, MO (US); and Hua Pan, St. Louis, MO (US)
Assigned to WASHINGTON UNIVERSITY, St. Louis, MO (US)
Filed by Washington University, St. Louis, MO (US)
Filed on Oct. 25, 2016, as Appl. No. 15/334,108.
Application 15/334,108 is a continuation in part of application No. 13/516,528, previously published as PCT/US2010/061103, filed on Dec. 17, 2010.
Claims priority of provisional application 62/249,126, filed on Oct. 30, 2015.
Claims priority of provisional application 61/287,582, filed on Dec. 17, 2009.
Prior Publication US 2017/0065669 A1, Mar. 9, 2017
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/10 (2006.01); A61K 9/51 (2006.01); A61K 45/06 (2006.01); A61K 38/06 (2006.01)
CPC A61K 38/10 (2013.01) [A61K 9/51 (2013.01); A61K 38/06 (2013.01); A61K 45/06 (2013.01)] 12 Claims
 
1. A method of inhibiting thrombin activation of a protein-activated receptor (PAR) in a subject, the method comprising administering to the subject an antithrombotic nanoparticle comprising a core and an outer layer,
wherein the core of the antithrombotic nanoparticle comprises a perfluorocarbon that is a liquid at about 37° C. and the outer layer comprises a mixture of a lipid and a surfactant;
wherein the exterior of the antithrombotic nanoparticle comprises a direct thrombin inhibitor covalently conjugated to the exterior via the lipid component of the nanoparticle's outer layer, such that the antithrombotic 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 antithrombotic nanoparticle is antithrombotic but does not substantially alter the clotting time of a subject's blood plasma.