Immobilized biologically active entities having high biological activity following mechanical manipulation
View Patent ↗Described are immobilized biologically active entities that retain significant biological activity following mechanical manipulation of a substrate material to which the entities are immobilized.
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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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.