Medical device capable of being compacted and expanded having anti-thrombin III binding activity

• US 8,986,713 B2
• Filed: 05/10/2007
• Issued: 03/24/2015
• 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): Naff, David M
• Application Number:
  US11/747,163
• Publication Number:
  US 20070264308A1
• Time in Patent Office: 2,875 Days
• US Class Current: 424/400
• 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 relates 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 medical device that is capable of being compacted and expanded;

a fluoropolymeric substrate material;

a plurality of layers of a polymeric covering material attached to at least a portion of a surface of said substrate material and cross-linked, a biologically active substance having anti-thrombin III binding activity of at least 5 picomoles per square centimeter (pmol/cm²) of substrate material covalently attached to at least a portion of said layers of said polymeric covering material; and

a biologically compatible glycosaminoglycan non-covalently combined with said polymeric covering material and said biologically active substance,

wherein said biologically active substance has an anti-thrombin III binding activity of at least 5 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material when measured following compaction of said medical device to 50% of said medical device'"'"'s original size and expansion of said medical device.

2. The medical device of claim 1 wherein said biologically active substance comprises a glycosaminoglycan.

3. The medical device of claim 1 wherein said biologically active substance comprises end-point attached heparin.

4. The medical device of claim 2 wherein at least a portion of said biologically compatible glycosaminoglycan 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.

5. The medical device of claim 1 wherein said device is sterilized.

6. The medical device of claim 1 wherein said biologically active substance has an anti-thrombin III binding activity of at least 6 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material when measured following said compaction and expansion of said medical device.

7. The medical device of claim 6 wherein said biologically active substance comprises a glycosaminoglycan.

8. The medical device of claim 6 wherein said biologically active substance comprises end-point attached heparin.

9. The medical device of claim 6 wherein at least a portion of said biologically compatible glycosaminoglycan 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.

10. The medical device of claim 1 wherein said biologically active substance has an anti-thrombin III binding activity of at least 7 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material when measured following said compaction and expansion of said medical device.

11. The medical device of claim 10 wherein said biologically active substance comprises a glycosaminoglycan.

12. The medical device of claim 10 wherein said biologically active substance comprises end-point attached heparin.

13. The medical device of claim 10 wherein at least a portion of said biologically compatible glycosaminoglycan 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.

14. The medical device of claim 1 wherein said biologically active substance has an anti-thrombin III binding activity of at least 8 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material when measured following said compaction and expansion of said medical device.

15. The medical device of claim 14 wherein said biologically active substance comprises a glycosaminoglycan.

16. The medical device of claim 14 wherein said biologically active substance comprises end-point attached heparin.

17. The medical device of claim 14 wherein at least a portion of said biologically compatible glycosaminoglycan 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.

18. The medical device of claim 1 wherein said biologically active substance has an anti-thrombin III binding activity of at least 9 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material when measured following said compaction and expansion of said substrate material.

19. The medical device of claim 18 wherein said biologically active substance comprises a glycosaminoglycan.

20. The medical device of claim 18 wherein said biologically active substance comprises end-point attached heparin.

21. The medical device of claim 18 wherein at least a portion of said biologically compatible glycosaminoglycan 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.

22. The medical device of claim 1 wherein said biologically active substance has an anti-thrombin III binding activity of at least 10 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material when measured following said compaction and expansion of said medical device.

23. The medical device of claim 22 wherein said biologically active substance comprises a glycosaminoglycan.

24. The medical device of claim 22 wherein said biologically active substance comprises end-point attached heparin.

25. The medical device of claim 22 wherein at least a portion of said biologically compatible glycosaminoglycan 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.

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