Immobilised biological entities

• US 8,501,212 B2
• Filed: 03/11/2011
• Issued: 08/06/2013
• Est. Priority Date: 03/12/2010
• Status: Active Grant

• Current Assignee: Carmeda AB
• Original Assignee: Carmeda AB
• Inventors: Vestberg, Robert
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US13/045,769
• Publication Number:
  US 20110223229A1
• Time in Patent Office: 879 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• 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, the coating layer being a biocompatible composition comprising an anti-coagulant entity capable of interacting with mammalian blood to prevent coagulation or thrombus formation, which anti-coagulant entity is covalently attached to the surface through a linker comprising a thioether.

Claims

1. A solid object having a surface which comprises an outer coating layer, said outer coating layer being a biocompatible composition comprising a polymer and a heparin moiety that interacts with mammalian blood to prevent coagulation or thrombus formation, wherein the heparin moiety is covalently attached to said polymer through a linker comprising a thioether, wherein the solid object has an antithrombin III binding activity of at least 1 picomole antithrombin III per square centimeter (pmol/cm²) of surface.

2. The solid object according to claim 1, wherein the heparin moiety is an end point attached heparin moiety.

3. The solid object according to claim 2, wherein the end point attached heparin moiety is connected through its reducing end.

4. The solid object according to claim 1, wherein the heparin moiety is a full length heparin.

5. The solid object according to claim 1, wherein the surface comprises two or more coating layers, only the outer coating layer being attached to the heparin moiety.

6. The solid object 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 to which the heparin moiety is covalently attached via a linker comprising a thioether.

7. The solid object according to claim 1, comprising a multiplicity of linkers of the same type.

8. The solid object according to claim 1, comprising a multiplicity of heparin moieties of the same type.

9. The solid object according to claim 1, wherein more than one heparin moiety is attached to a linker.

10. The solid object according to claim 1, wherein the coating comprises a polyamine as cationic polymer.

11. The solid object according to claim 10, wherein the coating comprises a layer of a high average molecular weight polyamine and a layer of an anionic polysaccharide as anionic polymer.

12. The solid object according to claim 10, wherein the polyamine is cross-linked

13. The solid object according to claim 1, which solid object comprises a metal or a synthetic or naturally occurring organic or inorganic polymer.

14. The solid object according to claim 1 which is a medical device.

15. The solid object according to claim 14, which is a sterile medical device for implantation, or other placement, at an anatomical site.

16. The solid object according to claim 1, wherein the object has an antithrombin III binding activity of at least 5 picomoles antithrombin III per square centimeter (pmol/cm²) of surface.