Immobilized biologically active entities having high biological activity following mechanical manipulation

• US 9,114,194 B2
• Filed: 05/12/2006
• Issued: 08/25/2015
• 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): Humphrey, Louise W
• Assistant Examiner(s): Srivastava, Kailash C
• Application Number:
  US11/433,250
• Publication Number:
  US 20070264302A1
• Time in Patent Office: 3,392 Days
• Field of Search: None
• US Class Current: 1/1
• 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

Described are 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 compacted and expanded medical device comprising:

a fluoropolymeric substrate material;

a polymeric covering material attached to at least a portion of a surface of said substrate material, a 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 polysaccharide non-covalently combined with said polymeric covering material and said biologically active entities,

wherein said biologically active entities have 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 plurality of biologically active entities comprise a glycosaminoglycan.

3. The medical device of claim 1, wherein said plurality of biologically active entities comprise end-point attached heparin.

4. The medical device of claim 1, wherein at least a portion of said biologically compatible organic polysaccharide 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 plurality of biologically active entities have an anti-thrombin III binding activity of at least 6 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material following said compaction and expansion of said substrate material.

6. The medical device of claim 5, wherein said plurality of biologically active entities comprise a glycosaminoglycan.

7. The medical device of claim 5, wherein said plurality of biologically active entities comprise end-point attached heparin.

8. The medical device of claim 5, wherein at least a portion of said biologically compatible organic polysaccharide 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.

9. The medical device of claim 1, wherein said plurality of biologically active entities have an anti-thrombin III binding activity of at least 7 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material following said compaction and expansion of said substrate material.

10. The medical device of claim 9, wherein said plurality of biologically active entities comprise a glycosaminoglycan.

11. The medical device of claim 9, wherein said plurality of biologically active entities comprise end-point attached heparin.

12. The medical device of claim 9, wherein at least a portion of said biologically compatible organic polysaccharide 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.

13. The medical device of claim 1, wherein said plurality of biologically active entities have an anti-thrombin III binding activity of at least 8 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material following said compaction and expansion of said substrate material.

14. The medical device of claim 13, wherein said plurality of biologically active entities comprise a glycosaminoglycan.

15. The medical device of claim 13, wherein said pluralities of biologically active entities comprise end-point attached heparin.

16. The medical device of claim 13, wherein at least a portion of said biologically compatible organic polysaccharide 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.

17. The medical device of claim 1, wherein said plurality of biologically active entities have an anti-thrombin III binding activity of at least 9 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material following said compaction and expansion of said substrate material.

18. The medical device of claim 17, wherein said plurality of biologically active entities comprise a glycosaminoglycan.

19. The medical device of claim 17, wherein said plurality of biologically active entities comprise end-point attached heparin.

20. The medical device of claim 17, wherein at least a portion of said biologically compatible organic polysaccharide 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.

21. The medical device of claim 1, wherein said plurality of biologically active entities have an anti-thrombin III binding activity of at least 10 picomoles anti-thrombin III per square centimeter (pmol/cm²) substrate material following said compaction and expansion of said substrate material.

22. The medical device of claim 21, wherein said plurality of biologically active entities comprise a glycosaminoglycan.

23. The medical device of claim 21, wherein said plurality of biologically active entities comprise end-point attached heparin.

24. The medical device of claim 21, wherein at least a portion of said biologically compatible organic polysaccharide 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.

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

26. The medical device of claim 1, wherein said fluoropolymeric material is polytetrafluoroethylene.

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

28. The medical device of claim 27, wherein said metallic composition is a nickel and titanium metal alloy.

29. The medical device of claim 27, wherein said metallic composition is stainless steel.

30. The medical device of claim 1, wherein said polymeric covering material comprise at least one layer of polyethylene imine.

31. A compacted and expanded medical device comprising:

a fluoropolymeric 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 biologically compatible polysaccharide non-covalently combined with said polymeric covering material and said first plurality of heparin molecules,

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 when measured following compaction of said medical device to 50% of said medical device'"'"'s original size and expansion of said medical device.

32. The medical device of claim 31, wherein at least a portion of said biologically compatible organic polysaccharide 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.

33. The medical device of claim 31, wherein said polymeric covering material comprise at least one layer of polyethylene imine.

34. The medical device of claim 31, wherein said polymeric covering material comprise multiple layers, wherein chemical components of at least one layer are cross-linked.

35. The medical device of claim 31, wherein said fluoropolymeric material is polytetrafluoroethylene.

36. The medical device of claim 31, wherein said substrate material is metallic in composition.

37. The medical device of claim 36, wherein said metallic composition is a nickel and titanium metal alloy.

38. The medical device of claim 36, wherein said metallic composition is stainless steel.