Polymer microspheres/nanospheres and encapsulating therapeutic proteins therein

• US 7,708,915 B2
• Filed: 10/13/2006
• Issued: 05/04/2010
• Est. Priority Date: 05/06/2004
• Status: Active Grant

• Current Assignee: Aphios Corporation
• Original Assignee: Aphios Corporation
• Inventors: Castor, Trevor P.
• Primary Examiner(s): Theisen; Mary Lynn F
• Application Number:
  US11/581,021
• Publication Number:
  US 20100074961A1
• Time in Patent Office: 1,299 Days
• Field of Search: None
• US Class Current: 264/5
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5192 Processes

Abstract

This invention is an improved process to formulate polymeric microspheres/nanospheres and encapsulate therapeutic proteins or other useful substances, and a polymer sphere apparatus. The invention is also methods of purifying protein-containing-polymeric-microspheres from unused polymer, and an apparatus therefore.

Claims

1. A method of purifying protein-containing-polymer-microspheres comprising

loading a PEG protein-containing-polymer-microspheres product into a column extractor;

pressurizing the extractor with a supercritical or near-critical fluid;

charging a first pump with a supercritical or near-critical fluid;

charging a second pump with a cosolvent;

pressurizing the pumps;

mixing the supercritical or near-critical fluid with the cosolvent under pressure;

flowing the fluid-cosolvent mixture through the extractor;

collecting PEG solubilized in cosolvent;

decompressing the extractor; and

recovering purified protein-containing-polymer-microspheres.

2. The method of claim 1, wherein said supercritical or near-critical fluid is selected from the group consisting of carbon dioxide, propane, fluorinated propane, Freon-23 and Freon 22.

3. The method of claim 1, wherein said cosolvent is ethanol or methanol.

4. The method of claim 1, wherein said fluid-cosolvent mixture comprises carbon dioxide:

ethanol;

;

70;

30.

5. The method of claim 1, wherein said pressure is about 2500 psig-5000 psig.

6. The method of claim 1, wherein the temperature is about 10°

C.-40°

C.