Stabilized enzyme compositions
View Patent ↗A medical device includes a base material having an immobilized fibrinolytic enzyme and dextran sulfate. The dextran sulfate has a molecular weight that is less than 40 kilo dalton (kDa). The medical device is formed from at least a base material. A fibrinolytic enzyme is immobilized on the base material. The fibrinolytic enzyme is stabilized with a dextran sulfate having a molecular weight of less than 40 (kDa).
1. A medical device comprising:
a base material including an immobilized fibrinolytic enzyme covalently bound to the base material and dextran sulfate, the medical device being for vascular implantation in a patient, the dextran sulfate having a molecular weight that is about 8 kilodaltons (kDa) to stabilize the fibrinolytic enzyme when in contact with blood of the patient.
2. The medical device according to claim 1 , wherein the fibrinolytic enzyme includes a urokinase-type plasminogen activator (uPA).
3. The medical device according to claim 1 , further comprising:
a combination of two or more antimicrobial agents impregnating the base material.
4. The medical device according to claim 3 , wherein the combination of two or more antimicrobial agents includes chlorhexidine base and a pharmaceutically acceptable salt thereof.
5. The medical device according to claim 1 , further comprising:
an antimicrobial agent impregnating the base material.
6. The medical device according to claim 5 , wherein the antimicrobial agent includes chlorhexidine base or a pharmaceutically acceptable salt thereof.
7. The medical device according to claim 5 , wherein the antimicrobial agent includes chlorhexidine diacetate.
8. The medical device according to claim 5 , wherein the antimicrobial agent includes chlorhexidine dodecanoate.
9. The medical device according to claim 5 , wherein the antimicrobial agent includes gentian violet.
10. The medical device according to claim 1 , further comprising:
a tubular structure including the base material.
11. The medical device according to claim 1 , wherein the base material is a polymer.
12. The medical device according to claim 11 , wherein the base material is a polyurethane.
13. A medical device comprising:
a polyurethane base material for vascular implantation in a patient:
an amount of a fibrinolytic enzyme sufficient to reduce the formation of blood clots in a patient, the fibrinolytic enzyme being immobilized by covalently binding the fibrinolytic enzyme in the base material;
a low molecular weight dextran sulfate to stabilize the fibrinolytic enzyme when in contact with blood of the patient, the low molecular weight dextran sulfate having a molecular weight of about 8 kilodaltons; and
a chlorhexidine base and/or a pharmaceutically acceptable salt thereof being disposed in the polyurethane base material in an amount sufficient to reduce microbial growth.
14. A medical device comprising:
a polyurethane base material for vascular implantation in a patient;
an amount of a urokinase-type plasminogen activator (uPA) sufficient to reduce the formation of blood clots in a patient, the uPA being covalently immobilized in the base material;
a low molecular weight dextran sulfate to stabilize the fibrinolytic enzyme when in contact with blood of the patient, the low molecular weight dextran sulfate having a molecular weight of about 8 kilodaltons; and
a chlorhexidine base and/or a pharmaceutically acceptable salt thereof being disposed in the polyurethane base material in an amount sufficient to reduce microbial growth.
15. A method of fabricating a medical device, the method comprising:
forming the medical device for vascular implantation in a patient from at least a base material;
immobilizing a fibrinolytic enzyme by covalently binding the fibrinolytic enzyme on the base material; and
stabilizing the fibrinolytic enzyme when in contact with blood of the patient with a dextran sulfate having a molecular weight of about 8 kilodaltons.
16. The method according to claim 15 , further comprising:
incubating the medical device in a fibrinolytic solution of the fibrinolytic enzyme and dextran sulfate.
17. The method according to claim 14 , further comprising:
preparing the fibrinolytic solution by dissolving about 30 units per micro liter of the fibrinolytic enzyme in a sodium acetate buffer, the fibrinolytic enzyme including urokinase-type plasminogen activator (uPA).
18. The method according to claim 15 , wherein the dextran sulfate is about 1% w/v fibrinolytic solution.
19. The method according to claim 15 , further comprising:
treating the base material to generate binding sites for covalently binding the fibrinolytic enzyme to the base material.
20. The method according to claim 17 , further comprising:
impregnating the base material with a combination of two or more antimicrobial agents.
21. The method according to claim 20 , further comprising:
impregnating the base material with the combination of chlorhexidine base and a pharmaceutically acceptable salt thereof.
22. The method according to claim 15 , further comprising:
impregnating the base material with an antimicrobial agent.
23. The method according to claim 22 , further comprising:
impregnating the base material with a chlorhexidine base or a pharmaceutically acceptable salt thereof.
24. The method according to claim 22 , further comprising:
impregnating the base material with chlorhexidine diacetate.
25. The method according to claim 22 , further comprising:
impregnating the base material with chlorhexidine dodecanoate.
26. The method according to claim 22 , further comprising:
impregnating the base material with gentian violet.
27. The method according to claim 22 , further comprising:
impregnating the base material with brilliant green.
28. The method according to claim 15 , further comprising:
forming a tubular structure from the base material.
29. The method according to claim 15 , further comprising:
wherein the base material includes a polymer.
30. The method according to claim 29 , further comprising:
wherein the polymer includes polyurethane.
31. The method according to claim 15 , further comprising:
immobilizing the fibrinolytic enzyme on a tip of the medical device.