Silyl and Heparin compositions

• US 6,630,580 B2
• Filed: 01/14/2002
• Issued: 10/07/2003
• Est. Priority Date: 09/22/1998
• Status: Expired due to Term

• Current Assignee: Biosurface Engineering Technologies, Inc. (Ferring Holding SA)
• Original Assignee: InnerDyne, Inc. (Medtronic Plc)
• Inventors: Tsang, Ray, Osaki, Shigemasa
• Primary Examiner(s): FONDA, KATHLEEN KAHLER
• Application Number:
  US10/047,118
• Publication Number:
  US 20020115836A1
• Time in Patent Office: 631 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 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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: A61L 33/08 Polysaccharides
• CPC Class Codes: C08B 37/0063 Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
• 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
• CPC Class Codes: C09D 105/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C09D 105/10 Heparin; Derivatives thereof

Abstract

The present invention provides an anti-thrombogenic and cellular-adhesion coating composition for blood-contacting surfaces. The coating comprises a covalent complex of from 1 to 30 hydrophobic silyl moieties of Formula I:

wherein R₁ is an C_1-18 alkyl or C_6-32 aryl group, each R₂ is independently selected from the group consisting of C_1-18 alkyl and C_6-32 aryl, R₃ is N or O, n is a number from 1 to 10, directly bound to a heparin molecule via covalent bonding, with an adhesive molecule directly bound to the heparin molecule. In one embodiment, the coating comprises benzyl-(1,2 dimethyl)disilyl heparin, wherein an adhesive molecule, such as fibronectin, is bound to the heparin.

Claims

1. A silyl and heparin covalent composition of Formula l:

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,

n is a number from 1 to 10, and

x is a number from 1 to 30.

2. The composition according to claim 1, wherein x is 1.

3. The composition according to claim 1, wherein x is from 2 to 25, whereby from 2 to 25 hydrophobic silyl moieties are covalently bound to one heparin molecule.

4. The composition according to claim 1, wherein R₁ is benzyl.

5. The composition according to claim 1, wherein each R₂ is an alkyl.

6. The composition according to claim 1, wherein n is 2 or 3.

7. The composition according to claim 1, which is [benzyl-tris(dimethylsilylmethyl)]-(N-heparinyl)-carbamate.

8. The composition according to claim 1, which is [benzyl-tris(dimethylsilylmethyl)]-(N-heparinyl)-carbamate.

9. The composition according to claim 1, which is dodecyl[benzyl-tris(dimethylsilylmethyl)]-(N-heparinyl)-carbamate.

10. The composition according to claim 1, wherein said heparin is a salt of heparin.

11. The composition according to claim 10, wherein said salt of heparin is selected from the group consisting of sodium heparin, calcium heparin, magnesium heparin and potassium heparin.

12. The composition according to claim 1, wherein said heparin is a derivative of heparin.

13. The composition according to claim 12, wherein said derivative of heparin is selected from the group consisting of ammonium heparin and benzalkonium heparin.

14. The composition according to claim 1, wherein R₃ is N, whereby attachment to the heparin molecule is through an amine of heparin.

15. The composition according to claim 1, wherein R₃ is O, whereby attachment to the heparin molecule is through a hydroxyl group of heparin.