Non-thrombogenic coating composition and methods for using same

• US 5,955,588 A
• Filed: 09/22/1998
• Issued: 09/21/1999
• Est. Priority Date: 12/22/1997
• Status: Expired due to Term

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: InnerDyne, Inc. (Medtronic Plc)
• Inventors: Tsang, Ray, Osaki, Shigemasa
• Primary Examiner(s): FONDA, KATHLEEN KAHLER
• Application Number:
  US09/159,276
• Time in Patent Office: 364 Days
• Field of Search: 536/21, 514/56, 523/112, 604/266, 427/2.1, 427/2.24, 427/2.25, 427/2.3
• US Class Current: 536/21
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C08G 77/60 in which all the silicon atoms are connected by linkages other than oxygen atoms
• CPC Class Codes: C08L 83/00 Compositions of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing silicon with or without sulfur, nitrogen, oxygen or carbon only; Compositions of derivatives of such polymers

Abstract

The present invention provides an anti-thrombogenic coating composition for blood-contacting surfaces. The coating comprises a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I: ##STR1## wherein R₁ is a C_1-8 alkyl or C_6-32 aryl group, each R₂ is independently selected from the group consisting of C_1-8 alkyl and C_6-32 aryl, R₃ is N or O, and n is a number from 1 to 10, directly bound to a heparin molecule via covalent bonding.

Claims

1. A non-thrombogenic coating composition for blood-contacting surfaces, said composition comprising a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I:

##STR7## wherein R₁ is a C_1-8 alkyl or C_6-32 aryl group,

each R₂ is independently selected from the group consisting of C_1-8 alkyl and C_6-32 aryl

R₃ is N or O, and

n is a number from 1 to 10 directly bound to sodium heparin via covalent bonding.

2. The composition according to claim 1, wherein said hydrophobic silyl moieties bind to said surfaces via hydrophobic bonding interactions.

3. The composition according to claim 1, wherein said complex comprises from 2 to 25 hydrophobic silyl moieties covalently bound to one heparin molecule.

4. The composition according to claim 1, wherein R₁ is benzyl in said hydrophobic silyl moiety of Formula I.

5. The composition according to claim 1, wherein each R₂ is an alkyl in said hydrophobic silyl moiety of Formula I.

6. The composition according to claim 1, wherein n is 2 or 3 in said hydrophobic silyl moiety of Formula I.

7. The composition according to claim 1, wherein said complex is benzyl-bis(dimethylsilylmethyl)!-(N-heparinyl)-carbamate.

8. The composition according to claim 1, wherein said complex is benzyl-tris(dimethylsilylmethyl)!-(N-heparinyl)-carbamate.

9. A non-thrombogenic medical device comprising surfaces for contacting blood, said surfaces having coated thereon a non-thrombogenic coating composition comprising a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I:

##STR8## wherein R₁ is a C_1-8 alkyl or C_6-32 aryl group,

each R₂ is independently selected from the group consisting of C_1-8 alkyl and C_6-32 aryl,

R₃ is N or O, and

n is a number from 1 to 10 directly bound to heparin via covalent bonding.

10. The device according to claim 9, wherein said hydrophobic silyl moieties bind to said surfaces via hydrophobic bonding interactions.

11. The device according to claim 9, wherein said complex comprises from 2 to 25 hydrophobic silyl moieties covalently bound to one heparin molecule.

12. The device according to claim 9, wherein R₁ is benzyl in said hydrophobic silyl moiety of Formula I.

13. The device according to claim 9, wherein each R₂ is an alkyl in said hydrophobic silyl moiety of Formula I.

14. The device according to claim 9, wherein n is 2 or 3 in said hydrophobic silyl moiety of Formula I.

15. The device according to claim 9, wherein said complex is benzyl-bis(dimethylsilylmethyl)!-(N-heparinyl)-carbamate.

16. The device according to claim 9, wherein said complex is benzyl-tris(dimethylsilylmethyl)!-(N-heparinyl)-carbamate.

17. The device according to claim 9, wherein said device is selected from the group consisting of oxygenators, oxygenator circuits, heart-lung bypass circuits, blood gas exchange devices, blood filters, artificial blood vessels, artificial valves, prosthetics, stents, catheters, heat exchangers, and hypodermic needles.

18. A method for rendering blood-contacting surfaces of a medical device non-thrombogenic, said method comprising coating said surfaces with a non-thrombogenic coating composition comprising a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I:

##STR9## wherein R₁ is a C_1-8 alkyl or C_6-32 aryl group,

each R₂ is independently selected from the group consisting of C_1-8 alkyl and C_6-32 aryl,

R₃ is N or O, and

n is a number from 1 to 10 directly bound to heparin via covalent bonding.

19. The method according to claim 18, wherein said hydrophobic silyl moieties bind to said surfaces via hydrophobic bonding interactions.

20. The method according to claim 18, wherein said complex comprises from 2 to 25 hydrophobic silyl moieties covalently bound to one heparin molecule.

21. The method according to claim 18, wherein R₁ is benzyl in said hydrophobic silyl moiety of Formula I.

22. The method according to claim 18, wherein each R₂ is an alkyl in said hydrophobic silyl moiety of Formula I.

23. The method according to claim 18, wherein n is 2 or 3 in said hydrophobic silyl moiety of Formula I.

24. The method according to claim 18, wherein said complex is benzyl-bis(dimethylsilylmethyl)!-(N-heparinyl)-carbamate.

25. The method according to claim 18, wherein said complex is benzyl-tris(dimethylsilylmethyl)!-(N-heparinyl)-carbamate.

26. The method according to claim 18, which further comprises the step of solubilizing said complex in a solvent prior to said step of coating said surface.

27. The method according to claim 18, wherein said step of coating said surface comprises dipping said surface into said coating composition comprising said complex.

28. The method according to claim 18, wherein said step of coating said surface comprises pumping said coating composition comprising said complex onto said surface.