Coating for substrate

• US 9,272,075 B2
• Filed: 02/04/2014
• Issued: 03/01/2016
• Est. Priority Date: 02/04/2013
• Status: Active Grant

• Current Assignee: WL Gore and Associates Incorporated (W.L. Gore and Associates)
• Original Assignee: WL Gore and Associates Incorporated (W.L. Gore and Associates)
• Inventors: Antoni, Per, Nystrom, Daniel, Vincent, Lars, Pietrzak, Krzysztof
• Primary Examiner(s): Yoon, Tae H
• Application Number:
  US14/172,342
• Publication Number:
  US 20140221522A1
• Time in Patent Office: 756 Days
• Field of Search: 428/355.EN, 524/105, 524/107
• US Class Current: 1/1
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/452 Lubricants
• CPC Class Codes: A61L 2400/10 Materials for lubricating medical devices
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• 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 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

There is provided inter alia a substrate with a surface having a hydrophilic coating comprising a cross-linked copolymer of components A and B, and optional components C and D; wherein

• component A comprises one or more C₂-C₁₆ hydrophilic monomers each bearing one or more alkene and/or alkyne groups;
• component B comprises one or more hydrophilic polymers each bearing two or more alkene and/or alkyne groups;
• component C, if present, comprises one or more beneficial agents each bearing one or more alkene or alkyne groups; and
• component D, if present, comprises one or more low molecular weight cross-linking agents each bearing two or more functional groups independently selected from thiol, alkene and alkyne groups;
• wherein the cross-linked copolymer is formed by radical polymerization involving the alkene and/or alkyne groups of components A, B and C (if present) and involving the functional groups of component D (if present);
• wherein the hydrophilic coating optionally comprises component E which comprises one or more beneficial agents, wherein component E does not form a copolymer with components A, B, C (if present) and D (if present);
• and wherein the hydrophilic coating is covalently attached to the surface of the substrate.

Claims

1. A substrate with a surface having a hydrophilic coating comprising a cross-linked copolymer of components A and B, and optional components C and D;

wherein

component A comprises one or more C₂-C₁₆ hydrophilic monomers each bearing one or more alkene and/or alkyne groups;

component B comprises one or more hydrophilic polymers each bearing two or more alkene and/or alkyne groups;

component C, if present, comprises one or more beneficial agents each bearing one or more alkene or alkyne groups; and

component D, if present, comprises one or more low molecular weight cross-linking agents each bearing two or more functional groups independently selected from thiol, alkene and alkyne groups;

wherein the cross-linked copolymer is formed by radical polymerisation involving the alkene and/or alkyne groups of components A, B and C (if present) and involving the functional groups of component D (if present);

wherein the hydrophilic coating optionally comprises component E which comprises one or more beneficial agents, wherein component E does not form a copolymer with components A, B, C (if present) and D (if present);

and wherein the hydrophilic coating is covalently attached to the surface of the substrate.

2. A substrate according to claim 1, wherein the covalent attachment between the surface of the substrate and the hydrophilic coating is formed via the reaction of surface-bound radicals on the surface of the substrate with a component of the hydrophilic coating, and wherein the surface bound radicals are generated via abstraction of hydrogen atoms from the surface of the substrate.

3. A substrate according to claim 1, having a first surface priming coating of polydopamine, to which the hydrophilic coating is covalently attached.

4. A substrate according to claim 1, wherein component A comprises one or more C₂-C₁₆ hydrophilic monomers each bearing one or more alkene and/or alkyne groups, and also one or more groups selected from ester, ether, carboxyl, hydroxyl, thiol, sulfonic acid, sulfate, amino, amido, phosphate, keto and aldehyde groups.

5. A substrate according to claim 4, wherein component A comprises acrylic acid and/or methacrylic acid.

6. A substrate according to claim 1, wherein component B comprises one or more hydrophilic polymers each bearing two or more alkene and/or alkyne groups, wherein the hydrophilic polymer is independently selected from the group consisting of hyaluronic acid, a hyaluronic acid derivative, poly-N-vinylpyrrolidone, a poly-N-vinylpyrrolidone derivative, a polyether derivative, polyvinylalcohol, and a polyvinylalcohol derivative.

7. A substrate according to claim 6, wherein component B comprises one or more PEG polymers each bearing two alkene groups.

8. A substrate according to claim 7 wherein component B comprises one or more diacrylate-functionalised PEG polymers.

9. A substrate according to claim 1, wherein component B comprises one or more hydrophilic polymers each bearing two or more alkene and/or alkyne groups, and wherein each hydrophilic polymer independently has molecular weight of 600-40,000 Da.

10. A substrate according to claim 1 wherein said beneficial agent of component C is an agent having pharmacological activity, a conductive agent or an adhesive agent.

11. A substrate according to claim 10, wherein the agent having pharmacological activity is an anti-thrombogenic agent, an anti-angiogenic agent, an anti-proliferative agent or an anti-microbial agent.

12. A substrate according to claim 1, wherein component D comprises one or more low molecular weight cross-linking agents each bearing two or more thiol groups.

13. A substrate according to claim 1, wherein said beneficial agent of component E is an agent having pharmacological activity, a conductive agent or an adhesive agent, wherein the agent having pharmacological activity is an anti-thrombogenic agent, an anti-angiogenic agent, an anti-proliferative agent or an anti-microbial agent.

14. A substrate according to claim 1, wherein the hydrophilic coating is lubricious and has a lubricity of <

100 g, using the Lubricity Test.

15. A substrate according to claim 14, wherein the hydrophilic coating has durability of <

50 g, using the Durability Test.

16. A substrate according to claim 1, wherein the substrate is a medical device.

21. A substrate according to claim 1, wherein the ratio of component B to component A is between 2.5:

1 and 0.5;

1 w/w.

22. A substrate according to claim 6, wherein the polyether derivative is polyethylene glycol (PEG), a polyethylene glycol (PEG) derivative, polypropylene glycol (PPG), or a polypropylene glycol (PPG) derivative.

23. A substrate according to claim 8, wherein the one or more diacrylate-functionalised PEG polymers are of formula (I):

24. A substrate according to claim 9, wherein each hydrophilic polymer independently has a molecular weight of 4,000-16,000 Da.

25. A substrate according to claim 11, wherein the agent having pharmacological activity is heparin.

17. A method of forming a hydrophilic coating which is covalently attached to the surface of a substrate;

wherein said method comprises the steps of;

(a) contacting the surface with a mixture comprising components A and B, optional component C, optional component D and a radical initiator;

wherein

component A comprises one or more C₂-C₁₆ hydrophilic monomers each bearing one or more alkene and/or alkyne groups;

component B comprises one or more hydrophilic polymers each bearing two or more alkene and/or alkyne groups;

component C, if present, comprises one or more beneficial agents each bearing one or more alkene or alkyne groups; and

component D, if present, comprises one or more low molecular weight cross-linking agents each bearing two or more functional groups independently selected from thiol, alkene and alkyne groups; and

(b) initiating radical polymerisation involving the alkene and/or alkyne groups of components A, B and C (if present) and involving the functional groups of component D (if present) in order to form a cross-linked copolymer of component A, component B, and optional components C and D;

wherein said copolymer is covalently linked to the surface; and

(c) optionally incorporating into the hydrophilic coating a component E which comprises one or more beneficial agents, wherein component E does not form a copolymer with components A, B, C (if present) and D (if present).

18. A method according to claim 17, wherein the substrate is a substrate having a surface comprising abstractable hydrogen atoms.

19. A method according to claim 17, wherein component A comprises one or more C₂-C₁₆ hydrophilic monomers each bearing one or more alkene and/or alkyne groups, and also one or more groups selected from ester, ether, carboxyl, hydroxyl, thiol, sulfonic acid, sulfate, amino, amido, phosphate, keto and aldehyde groups, and wherein component B comprises one or more hydrophilic polymers each bearing two or more alkene and/or alkyne groups, wherein the hydrophilic polymer is independently selected from the group consisting of hyaluronic acid, a hyaluronic acid derivative, poly-N-vinylpyrrolidone, a poly-N-vinylpyrrolidone derivative, a polyether derivative, polyvinylalcohol, and a polyvinylalcohol derivative.

20. A substrate with a hydrophilic coating obtainable according to the method of claim 17.

26. A method according to claim 19, wherein component A comprises acrylic acid and/or methacrylic acid and component B comprises one or more PEG polymers each bearing two alkene groups.

27. A method according to claim 19, wherein the polyether derivative is polyethylene glycol (PEG), a polyethylene glycol (PEG) derivative, polypropylene glycol (PPG) or a polypropylene glycol (PPG) derivative.