Immobilised biological entities

• US 10,016,512 B2
• Filed: 06/06/2013
• Issued: 07/10/2018
• Est. Priority Date: 03/12/2010
• Status: Active Grant

• Current Assignee: Carmeda AB (W.L. Gore and Associates)
• Original Assignee: Carmeda AB (W.L. Gore and Associates)
• Inventors: Vestberg, Robert
• Primary Examiner(s): Pallay, Michael B
• Application Number:
  US13/911,727
• Publication Number:
  US 20130273122A1
• Time in Patent Office: 1,860 Days
• 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, said 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 said surface through a linker comprising a thioether.

Claims

1. A process for the production of a solid object having a surface which comprises an outer coating layer, said outer coating layer being a biocompatible composition comprising a polymer and an anti-coagulant entity capable of interacting with mammalian blood to prevent coagulation or thrombus formation, which anti-coagulant entity is covalently attached to said polymer through a linker comprising a thioether;

which process comprises the reaction of a corresponding anti-coagulant entity carrying an alkene or alkyne group with a corresponding surface carrying a thiol group, or the reaction of a corresponding anti-coagulant entity carrying a thiol group with a corresponding surface carrying an alkene or alkyne group.

2. A process according to claim 1 comprising:

(a) treating a solid object to present a surface comprising a cationic polymer outer coating layer which has been functionalized to bear thiol groups;

(b) reacting said cationic polymer outer coating layer which has been functionalized to bear thiol groups with an anti-coagulant entity which is functionalized to bear an alkene or alkyne group;

thereby to attach the anti-coagulant entity to the cationic polymer through a linker comprising a thioether.

3. A process according to claim 1 comprising:

(a) treating a solid object to present a cationic polymer outer coating layer which has been functionalized to bear alkene or alkyne groups;

(b) reacting said cationic polymer outer coating layer which has been functionalized to bear alkene or alkyne groups with an anti-coagulant entity which is functionalized to bear a thiol group;

thereby to attach the anti-coagulant entity to the cationic polymer through a linker comprising a thioether.

4. A process according to claim 1 comprising:

(a) treating a solid object to present a cationic polymer surface layer;

(b) associating with said cationic polymer surface layer a functionalized cationic polymer bearing a multiplicity of negatively charged anti-coagulant entities which are attached thereto via a linker comprising a thioether, said cationic polymer bearing a multiplicity of negatively charged anti-coagulant entities and said functionalized cationic polymer having a net negative charge.

5. A process according to claim 1 comprising:

(a) treating a solid object to present an anionic polymer surface layer;

(b) associating with said anionic polymer surface layer a functionalized cationic polymer bearing a multiplicity of negatively charged anti-coagulant entities which are attached thereto via a linker comprising a thioether, said functionalized cationic polymer bearing a multiplicity of negatively charged anti-coagulant entities and having a net positive charge.

6. A process according to claim 5, wherein the anionic polymer is dextran sulfate or a derivative thereof.

7. A process according to claim 2, wherein the cationic polymer is a polyamine.

8. A process according to claim 1, wherein the solid object is a medical device.

9. A process according to claim 1, wherein the solid object has a surface which comprises one or more layers of polysaccharide and polyamine, which process comprises the reaction of a corresponding surface having an outer layer of polysaccharide which has a net negative charge with a polyamine, carrying a corresponding anti-coagulant entity through a linker comprising a thioether, having a net positive charge.

10. A process according to claim 1, wherein the solid object has a surface which comprises one or more layers of polysaccharide and polyamine, which process comprises the reaction of a corresponding surface having an outer layer of polysaccharide which has a net negative charge with a polyamine carrying an thiol or an alkene or alkyne group which has a net positive charge and reacting the resulting product with an anti-coagulant entity carrying an alkene or alkyne or a thiol group respectively.

11. A process according to claim 1, wherein the solid object has a surface which comprises one or more layers of polysaccharide and polyamine, which process comprises the reaction of a corresponding surface having an outer layer of polyamine having a net positive charge with a polyamine carrying a multiplicity of corresponding anti-coagulant entities through a linker comprising a thioether such that said polyamine has a net negative charge.

12. A process according to claim 4 wherein the negatively charged anti-coagulant entities are heparin moieties.

13. A process according to claim 5 wherein the negatively charged anti-coagulant entities are heparin moieties.