Immobilized biologically active entities having a high degree of biological activity

• US 8,409,604 B2
• Filed: 08/11/2011
• Issued: 04/02/2013
• 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.
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US13/208,220
• Publication Number:
  US 20110293689A1
• Time in Patent Office: 600 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/1709 from mammals
• 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 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 27/20 Polysaccharides
• 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: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C08L 5/02 Dextran; Derivatives thereof
• CPC Class Codes: C08L 5/10 Heparin; Derivatives thereof

Abstract

The present invention relates to immobilized biologically active entities having heparin cofactor II binding activity.

Claims

1. A medical device comprising:

a substrate material;

a polymeric covering material attached to at least a portion of a surface of said substrate material, a first plurality of biologically active entities having heparin cofactor II binding activity and a second plurality of biologically active entities having anti-thrombin III binding activity covalently attached to at least a portion of said polymeric covering material; and

a biologically compatible composition combined with said polymeric covering material,

wherein said biologically active entities have a heparin cofactor II binding activity of at least 5 picomoles heparin cofactor II per square centimeter (pmol/cm²) and at least 5 picomoles anti-thrombin III per square centimeter.

2. The medical device of claim 1 wherein said biologically compatible composition is covalently combined with said polymeric covering material.

3. The medical device of claim 1 wherein said biologically compatible composition is non-covalently combined with said polymeric covering material.

4. The medical device of claim 1 wherein said first plurality of biologically active entities comprises a glycosaminoglycan.

5. The medical device of claim 1 wherein said first plurality of biologically active entities comprises dermatan disulfate.

6. The medical device of claim 1 wherein said first plurality of biologically active entities comprises end-point attached dermatan disulfate.

7. The medical device of claim 1 wherein at least a portion of said biologically compatible composition 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.

8. The medical device of claim 1 wherein said biologically compatible composition comprises an organic compound.

9. The medical device of claim 8 wherein said organic compound is a polysaccharide.

10. The medical device of claim 9 wherein said polysaccharide is a glycosaminoglycan.

11. The medical device of claim 8 wherein said polysaccharide is dextran.

12. The medical device of claim 9 wherein said polysaccharide is dextran sulfate.

13. The medical device of claim 1 wherein said biologically compatible composition is polyethylene glycol.

14. The medical device of claim 1 wherein said biologically compatible composition is an antiproliferative agent.

15. The medical device of claim 14 wherein said antiproliferative agent is dexamethasone.

16. The medical device of claim 1 wherein said biologically compatible composition comprises a synthetic non-polar molecule.

17. The medical device of claim 1 wherein said biologically compatible composition comprises an inorganic compound.

18. The medical device of claim 17 wherein said inorganic compound comprises a phosphate.

19. The medical device of claim 1 wherein said first plurality of biologically active entities have a heparin cofactor II binding activity of at least 5 picomoles heparin cofactor II per square centimeter (pmol/cm²) substrate material following sterilization of said substrate material.

20. The medical device of claim 1 wherein said first plurality of biologically active entities have a heparin cofactor II binding activity of at least 5 picomoles heparin cofactor II per square centimeter (pmol/cm²) substrate material following compaction and expansion of said substrate material.

21. The medical device of claim 1 wherein said biologically compatible composition comprises the co-immobilization of heparin and dermatan disulfate.