Artificial platelets for treating catastrophic bleeding

• US 11,112,145 B2
• Filed: 09/24/2015
• Issued: 09/07/2021
• Est. Priority Date: 09/24/2014
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Liu, Ying, Donovan, Alexander
• Primary Examiner(s): Ricci, Craig D
• Application Number:
  US15/513,752
• Publication Number:
  US 20180180328A1
• Time in Patent Office: 2,175 Days
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: A61K 38/36 Blood coagulation or fibrinolysis factors
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1278 Post-loading, e.g. by ion or pH gradient
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: F16K 49/005 Circulation means for a separate heat transfer fluid
• CPC Class Codes: F25B 9/04 using vortex effect
• CPC Class Codes: G05D 23/1919 characterised by the type of controller

Abstract

Artificial dense granules composed of a sterically stabilized liposome shell encapsulating a polyphosphate nanoparticle core are provided as are methods for their production and use in the treatment of a severe hemorrhagic event.

Claims

1. A composition comprising a sterically stabilized liposome shell encapsulating an inorganic polyphosphate nanoparticle core, wherein:

(a) the sterically stabilized liposome shell comprises polyethylene glycol covalently conjugated to a glycerophospholipid; and

(b) the inorganic polyphosphate nanoparticle core is prepared by;

precipitating inorganic polyphosphate under aqueous conditions at physiological pH and salt conditions to form nanoparticles, wherein the inorganic polyphosphate has

2. The composition of claim 1, wherein the sterically stabilized liposome shell further comprises a phospholipid, a sterol, an amine-functionalized lipid or polymer, amphiphilic peptide, polyelectrolyte, amphiphilic copolymer or a derivative or combination thereof.

3. The composition of claim 1, wherein the sterically stabilized liposome shell comprises phosphatidylcholine and 1,2-di-palmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000].

4. The composition of claim 1, wherein the sterically stabilized liposome shell comprises cholesterol.

5. A kit comprising the composition of claim 1.

6. The composition of claim 1, wherein the inorganic polyphosphate nanoparticle core is a precipitated particle of polyphosphate that is between 100 nm and 250 nm in diameter.