Medical device capable of being compacted and expanded having anti-thrombin III binding activity
View Patent ↗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.
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/cm 2 ) 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/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 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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/cm 2 ) 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.