Immobilised biological entities

• US 10,064,978 B2
• Filed: 09/19/2014
• Issued: 09/04/2018
• Est. Priority Date: 09/15/2008
• Status: Active Grant

• Current Assignee: Carmeda AB
• Original Assignee: Carmeda AB
• Inventors: Oscarson, Stefan, Lahmann, Martina, Leontein, Karin, Vestberg, Robert
• Primary Examiner(s): FALKOWITZ, ANNA R
• Application Number:
  US14/490,891
• Publication Number:
  US 20150045508A1
• Time in Patent Office: 1,446 Days
• 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 process for preparing a non-thrombogenic medical device comprising:

(a) treating a medical device to present a cationic polymer surface layer which has been functionalized to bear azido groups; and

(b) reacting said cationic polymer surface layer which has been functionalized to bear azido groups with an anti-coagulant entity which is functionalized to bear an alkyne group;

thereby to covalently attach the anti-coagulant entity at its end point through position C1 of its reducing terminal to the device through a link comprising a 1,2,3-triazole wherein the anti-coagulant entity is a heparin moiety; and

wherein the device has an antithrombin III binding activity of at least 2 picomoles antithrombin III per square centimeter (pmol/cm²) of surface.

3. A process according to claim 1 wherein the cationic polymer is a polyamine.

4. A process according to claim 1 wherein the entity is a full length heparin.

5. A process according to claim 3 wherein the coating comprises a layer of a high average molecular weight polyamine and a layer of an anionic polysaccharide as anionic polymer.

6. A process according to claim 1, wherein the device is a sterile medical device for implantation, or other placement, at an anatomical site.

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

2. A process for the production of 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 at its end point through C1 of its reducing terminal to said surface through a link comprising a 1,2,3-triazole wherein the process comprises the reaction of a corresponding entity carrying an alkyne group with a corresponding surface carrying an azido group, wherein the entity capable of interacting with mammalian blood to prevent coagulation or thrombus formation is a heparin moiety, and wherein the device has an antithrombin III binding activity of at least 2 picomoles antithrombin III per square centimeter (pmol/cm²) of surface.