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)
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.