Artificial platelets for treating catastrophic bleeding

Patent metadata

Field	Value
Publication number	US-11112145-B2
Application number	US-201515513752-A
Country	US
Kind code	B2
Filing date	Sep 24, 2015
Priority date	Sep 24, 2014
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

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.

First claim

What is claimed is:

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

the structure wherein n is at least 100 and the physiological salt is calcium chloride, thereby producing an inorganic polyphosphate nanoparticle core consisting of calcium, phosphate and oxygen.

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.

Assignees

• Univ Illinois

Inventors

• Liu Ying
• Donovan Alexander

Classifications

• A61K38/36 Primary

  Blood coagulation or fibrinolysis factors · CPC title

• A61K9/1278

  Post-loading, e.g. by ion or pH gradient · CPC title

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K33/42

  Phosphorus; Compounds thereof · CPC title