Immobilised biological entities

• US 8,992,963 B2
• Filed: 09/15/2009
• Issued: 03/31/2015
• Est. Priority Date: 09/15/2008
• Status: Active Grant

• Current Assignee: Carmeda AB
• Original Assignee: Carmeda AB
• Inventors: Oscarson, Stefan, Lahmann, Martina, Vestberg, Robert, Leontein, Karin
• Primary Examiner(s): Singh, Anoop
• Assistant Examiner(s): FALKOWITZ, ANNA R
• Application Number:
  US12/559,660
• Publication Number:
  US 20100074938A1
• Time in Patent Office: 2,023 Days
• Field of Search: 424/400, 424/423, 424/424, 514/56
• US Class Current: 424/423
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2400/04 Materials for stopping bleeding
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0035 using a polymer with positively charged atoms in the polymeric backbone, e.g. ionenes
• CPC Class Codes: A61L 33/0076 Chemical modification of the substrate
• CPC Class Codes: A61L 33/068 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L33/062 takes precedence
• CPC Class Codes: A61L 33/08 Polysaccharides
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

There is described inter alia a medical device having a surface which comprises a coating layer, said coating layer being a biocompatible composition comprising an entity capable of interacting with mammalian blood to prevent coagulation or thrombus formation, which entity is covalently attached to said surface through a link comprising a 1,2,3-triazole.

Claims

1. A medical device having a surface which comprises a coating layer, said coating layer being a biocompatible composition comprising a heparin moiety which is covalently end point attached through position C1 of its reducing terminal to said surface through a link comprising a 1,2,3-triazole wherein the device has an antithrombin III binding activity of at least 2 picomoles antithrombin III per square centimeter (pmol/cm²) of surface.

2. A device according to claim 1, wherein the heparin moiety is a full length heparin.

3. A device according to claim 1, wherein the surface comprises two or more coating layers, only the outer coating layer being attached to the heparin moiety.

4. A device according to claim 1 wherein the surface comprises one or more coating bilayers of cationic polymer and anionic polymer, the innermost layer being a layer of cationic polymer and the outermost layer being a layer of cationic polymer covalently attached to the heparin moiety.

5. A device according to claim 1, comprising a multiplicity of links of the same type.

6. A device according to claim 1, wherein more than one heparin moiety is attached to each link.

7. A device according to claim 1, wherein the coating comprises a polyamine as cationic polymer.

8. A device according to claim 7, wherein the coating comprises a layer of a high average molecular weight polyamine and a layer of an anionic polysaccharide as anionic polymer.

9. A device according to claim 7, wherein the polyamine is cross-linked.

10. A device according to claim 1, which device comprises a metal or a synthetic or naturally occurring organic or inorganic polymer.

11. A device according to claim 1, which device is a sterile medical device for implantation, or other placement, at an anatomical site.

12. A device according to claim 1, wherein the medical device has an antithrombin III binding activity of at least 5 picomoles e.g. at least 10 picomoles antithrombin III per square centimeter (pmol/cm²) of surface.

13. A non-thrombogenic medical device having a surface comprising a functionalized cationic polymer outer layer whereby heparin moiety is end point attached at position C1 of its reducing terminal to the cationic polymer outer layer through a link comprising a 1,2,3-triazole wherein the device has an antithrombin III binding activity of at least 2 picomoles antithrombin III per square centimeter (pmol/cm²) of surface.

14. A non thrombogenic medical device according to claim 13 wherein the cationic polymer is a polyamine.

15. A non thrombogenic medical device according to claim 13 wherein the heparin moiety is a full length heparin moiety.