LAYERED NON-FOULING, ANTIMICROBIAL ANTITHROMBOGENIC COATINGS

• US 20100145286A1
• Filed: 12/07/2009
• Published: 06/10/2010
• Est. Priority Date: 12/05/2008
• Status: Active Grant

• Current Assignee: Arrow International Incorporated (Teleflex Incorporated)
• Original Assignee: Semprus BioSciences Corp. (Teleflex Incorporated)
• Inventors: Bouchard, Michael, Hencke, Michael, Huval, Chad, Squier, Trevor, Loose, Christopher R., O'Shaughnessey, William Shannan, Li, Jun, Zhang, Zheng
• Granted Patent: US 8,308,699 B2
• Time in Patent Office: Days
• US Class Current: 604/265
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 17/145 Coating
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• 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 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C09D 5/1637 Macromolecular compounds
• CPC Class Codes: C09D 5/1693 as part of a multilayer system
• CPC Class Codes: Y10T 428/31507 Of polycarbonate
• CPC Class Codes: Y10T 428/31511 Of epoxy ether
• CPC Class Codes: Y10T 428/31544 Addition polymer is perhalogenated
• CPC Class Codes: Y10T 428/31576 Ester monomer type [polyvinylacetate, etc.]
• CPC Class Codes: Y10T 428/31663 As siloxane, silicone or silane
• CPC Class Codes: Y10T 428/31667 : Next to addition polymer from unsaturated monomers, or aldehyde or ketone condensation product
• CPC Class Codes: Y10T 428/31699 : Ester, halide or nitrile of addition polymer
• CPC Class Codes: Y10T 428/31725 : Of polyamide
• CPC Class Codes: Y10T 428/31743 : Next to addition polymer from unsaturated monomer[s]
• CPC Class Codes: Y10T 428/3175 : Next to addition polymer from unsaturated monomer[s]
• CPC Class Codes: Y10T 428/31786 : Of polyester [e.g., alkyd, etc.]
• CPC Class Codes: Y10T 428/31797 : Next to addition polymer from unsaturated monomers
• CPC Class Codes: Y10T 428/31913 : Monoolefin polymer
• CPC Class Codes: Y10T 428/31928 : Ester, halide or nitrile of addition polymer
• CPC Class Codes: Y10T 442/2525 : Coating or impregnation functions biologically [e.g., insect repellent, antiseptic, insecticide, bactericide, etc.]

Abstract

Substrates, optionally coated with an undercoating, having grafted thereto one or more non-fouling materials are described herein. The non-fouling, polymeric material can be grafted to a variety of functionalized substrate materials, particularly polymeric substrates and/or polymeric undercoatings immobilized on a substrate. The compositions described herein are highly resistant protein absorption, particularly in complex media and retain a high degree of non-fouling activity over long periods of time. The compositions described herein may also demonstrate antimicrobial and/or anti-thrombogenic activity. The non-fouling material can be grafted to a functionalized substrate, or optionally from an undercoating on the substrate, preferably without significantly affecting the mechanical and/or physical properties of the substrate material

Claims

1. A composition comprising a functionalized substrate having covalently bound thereto a non-fouling polymeric top coat,

2. The composition of claim 1, wherein the substrate is selected from the group consisting of metallic materials, ceramics, polymers, woven materials, non-woven materials, silicon, and combinations thereof.

3. The composition of claim 2, wherein the metallic material is selected from the group consisting of titanium and alloys thereof, stainless steel, tantalum, palladium, zirconium, niobium, molybdenum, nickel-chrome, cobalt or alloys thereof, and combinations thereof.

4. The composition of claim 2, wherein the ceramic is selected from the group consisting of oxides, carbides, or nitrides of the transition metal elements or metalloid elements.

5. The composition of claim 2, wherein the polymer is selected from the group consisting of polystyrene and substituted polystyrenes, poly(urethane)s, polyacrylates and polymethacrylates, polyacrylamides and polymethacrylamides, polyesters, polysiloxanes, polyethers, poly(orthoester), poly(carbonates), poly(hydroxyalkanoate)s, polyfluorocarbons, PEEK, Teflon, silicones, epoxy resins, polyamides and copolymers thereof, nylon, polyalkenes, phenolic resins, PTFE, natural and synthetic elastomers, adhesives and sealants, polyolefins, polysulfones, polyacrylonitrile, polysaccharides, and combinations thereof.

6. The composition of claim 5, wherein the polymer is polyurethane or polycarbonate-based polyurethanes.

7. The composition of claim 1, wherein the substrate is functionalized with one or more undercoats.

8. The composition of claim 7, wherein the undercoating comprises reactive functional groups and/or a polymeric material comprising reactive functional groups.

9. The composition of claim 8, wherein the undercoat is a polymeric material comprising reactive functional groups.

10. The composition of claim 9, wherein the undercoating comprises one or more monomers selected from the group consisting of acrylates, acrylamides, vinyl compounds, di, tri-, and tetra-isocyanates, alcohols, amines, and thiocyanates;

lactones, lactams, and combinations thereof.

11. The composition of claim 10, wherein the undercoating comprises one or more acrylate monomers.

12. The composition of claim 11, wherein the undercoating comprises a copolymer of glycidyl methacrylate (GMA), 2-hydroxypropyl methacrylate (HPMA), lauryl methacrylate (LMA), and trimethoxysilyl methacrylate (TMOSMA).

13. The composition of claim 1, wherein the non-fouling polymeric material is a copolymer.

14. The composition of claim 13, wherein the copolymer comprises greater than 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, or 99.99% non-fouling moieties by molar ratio of the polymer.

15. The composition of claim 14, wherein the copolymer is a zwitterionic polymer.

16. The composition of claim 15, wherein copolymer comprises one or more monomers having the formula

17. The composition of claim 16, wherein ZI is selected from the group consisting of:

18. The composition of claim 17, wherein the copolymer further comprises one or more monomers selected from the group consisting of acrylates, acrylamides, vinyl compounds, di, tri-, and tetra-isocyanates, alcohols, amines, and thiocyanates;

lactones, lactams, and combinations thereof.

19. The composition of claim 18, wherein the copolymer comprises 25-70 mol % sulfobetaine methacrylate, 10-50 mol % glycidyl methacrylate methacrylate, and 0-50 mol % 2-hydroxypropyl methacrylate.

20. The composition of claim 1, wherein the non-fouling polymeric material is grafted to the undercoating through a tether.

21. The composition of claim 20, wherein the tether is part of the non-fouling polymeric material.

22. The composition of claim 20, wherein the tether is a moiety immobilized on the undercoat.

23. The composition of claim 1, wherein the non-fouling polymeric material is in the form of a brush or a comb.

24. The composition of claim 1, wherein the non-fouling polymeric material, the undercoat, functionalized substrate, or combinations thereof have immobilized thereon one or more bioactive agents.

25. The composition of claim 21, wherein the one or more bioactive agents are immobilized covalently or non-covalently on the non-fouling material, undercoat, functionalized substrate, or combinations thereof.

26. The composition of claim 25, wherein the one or more bioactive agents are immobilized to the topcoating, the undercoating, the functionalized substrate, or combinations thereof, through a tether.

27. The composition of claim 1, wherein the composition reduces fouling by greater than 80%, 85%, 90%, 95%, or 99%, after storage in phosphate buffered saline (PBS) containing protein, media, serum, or in vivo at 37°

C. for a period of at least compared to uncoated substrate.

28. The composition of claim 1, wherein the composition is biocompatible.

29. The composition of claim 1, wherein the composition is antimicrobial.

30. The composition of claim 1, wherein the composition is anti-thrombogenic.

31. The composition of claim 1, wherein the composition retains greater than 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% of its original material properties, such as surface contact angle, non-fouling, anti-thrombogenic, and/or antimicrobial activity, in PBS containing protein, media, serum, or in vivo for a time of 1, 7, 14, 30, 90, 365, or 1000 days.

32. The composition of claim 1, wherein the composition is in the form of a medial device.

33. The composition of claim 32, wherein the medical device is selected from the group consisting of fibers;

surgical, medical or dental instruments;

blood oxygenators, ventilators, pumps, drug delivery devices, tubing, wiring, electrodes, contraceptive devices, feminine hygiene products, endoscopes, grafts, stents, stent grafts, pacemakers, implantable cardioverter-defibrillators, cardiac resynchronization therapy devices, cardiovascular device leads, ventricular assist devices and drivelines, heart valves, vena cava filters, endovascular coils, catheters, catheter connectors and valves, intravenous delivery lines and manifolds, shunts, wound drains, dialysis membranes, infusion ports, cochlear implants, endotracheal tubes, tracheostomy tubes, ventilator breathing tubes and circuits, guide wires, fluid collection bags, drug delivery bags and tubing, implantable sensors, ophthalmic devices, orthopedic devices, dental implants, periodontal implants, breast implants, penile implants, maxillofacial implants, cosmetic implants, valves, appliances, scaffolding, suturing material, needles, hernia repair meshes, tension-free vaginal tape and vaginal slings, prosthetic neurological devices, tissue regeneration or cell culture devices, or other medical devices used within or in contact with the body.

34. The composition of claim 33, wherein the device contains lumens, cavities, porous structures, or combinations thereof.

35. The composition of claim 34, wherein the device is a vascularly inserted catheter selected from the group consisting of a peripherally inserted central catheter (PICC), central venous catheter (CVC), and hemodialysis catheter.

36. The composition of claim 1, wherein the tensile strength, modulus, device dimensions, or combinations thereof are within 20%, 10%, 5%, or 1% of the tensile strength, modulus, device dimensions, or combinations thereof of the uncoated substrate.

37. A method of making the composition of claim 1, comprising grafting to the undercoating a non-fouling polymeric material.

38. The method of claim 37, wherein the polymeric material is grafted to the surface using one or more monomers having unsaturated bonds.