IMMOBILIZED BIOLOGICALLY ACTIVE ENTITIES HAVING HIGH BIOLOGICAL ACTIVITY FOLOWING MECHANICAL MANIPULATION

• US 20090181066A1
• Filed: 03/24/2009
• Published: 07/16/2009
• Est. Priority Date: 05/12/2006
• Status: Active Grant

• Current Assignee: W. L. Gore & Associates (W.L. Gore & Associates)
• Original Assignee: W. L. Gore & Associates (W.L. Gore & Associates)
• Inventors: Cleek, Robert L., Daly, Michael D., Pietrzak, Krzysztof R.
• Granted Patent: US 9,399,085 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08L 79/02 Polyamines
• CPC Class Codes: Y10T 428/31544 Addition polymer is perhalogenated

Abstract

The present invention is directed to immobilized biologically active entities that retain significant biological activity following mechanical manipulation of a substrate material to which the entities are immobilized.

Claims

1. A medical device comprising:

a polymeric substrate material;

a polymeric covering material attached to at least a portion of a surface of said substrate material;

a first plurality of heparin molecules having anti-thrombin III binding activity end point attached to at least a portion of said polymeric covering material; and

a composition comprising a second plurality of heparin molecules non-covalently combined with said polymeric covering material,

wherein said first plurality of heparin molecules have an anti-thrombin III binding activity of at least 10 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material following compaction and expansion of said substrate material.

2. The medical device of claim 1 wherein at least a portion of said second plurality of heparin molecules is released from said medical device in a 0.15M phosphate buffer solution having a temperature of about thirty-seven degrees centigrade and a substantially neutral pH.

3. The medical device of claim 1 wherein said polymeric covering material comprises multiple layers, wherein chemical components of at least one layer are cross-linked.

4. The medical device of claim 1 wherein said substrate material is polymeric in composition.

5. The medical device of claim 4 wherein said polymeric substrate material is fluoropolymeric in composition.

6. The medical device of claim 5 wherein said fluoropolymeric material is polytetrafluoroethylene.

7. The medical device of claim 1 wherein said substrate material is metallic in composition.

8. The medical device of claim 7 wherein said metallic composition is a nickel and titanium metal alloy.

9. The medical device of claim 7 wherein said metallic composition is stainless steel.

10. The medical device of claim 1 wherein further comprising an antiproliferative agent.

11. The medical device of claim 10 wherein said antiproliferative agent is dexamethasone.

12. The medical device of claim 1 wherein said polymeric covering material comprises at least one layer of polyethylene imine.