Medical device coatings

• US 9,155,735 B2
• Filed: 08/25/2011
• Issued: 10/13/2015
• Est. Priority Date: 08/25/2010
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: TYRX, INC. (Medtronic Plc)
• Inventors: Pulapura, Satish, Ge, Qing
• Primary Examiner(s): SANDERS, KRIELLION ANTIONETTE
• Application Number:
  US13/218,096
• Publication Number:
  US 20120052292A1
• Time in Patent Office: 1,510 Days
• Field of Search: 523/105, 523/113, 523/122, 424/400, 424/618, 428/336, 428/457, 514/152, 514/254.1, 514/254, 514/635, 514/772
• US Class Current: 1/1
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• 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
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 67/02 : Polyesters derived from dicarboxylic acids and dihydroxy compounds C08L67/06 takes precedence
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides
• CPC Class Codes: C09D 171/02 : Polyalkylene oxides
• CPC Class Codes: C09D 5/14 : Paints containing biocides, e.g. fungicides, insecticides or pesticides C09D5/16 takes precedence
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10T 428/265 : 1 mil or less
• CPC Class Codes: Y10T 428/31678 : Of metal

Abstract

The present invention relates to coatings comprising polyethylene glycol and at least one polyphenolic polymer. In particular, the polyphenolic polymer could be selected from the group consisting of tyrosine-derived polyarylates, linear polyesteramides, dihydroxybenzoate polymers, and resorcinol-derived polymers. The coating of the present invention may also include a drug, such as an antibiotic. The coatings of the present invention are suitable for use as coatings for medical devices, such as orthopedic pins or stents.

Claims

1. A coating comprising polyethylene glycol and at least one polyphenolic polymer, wherein the polyethylene glycol is selected from the group consisting of PEG-3350, PEG-1000, and PEG-400.

2. The coating of claim 1, wherein the polyphenolic polymer is selected from the group consisting of tyrosine-derived polyarylates, linear polyesteramides, dihydroxybenzoate polymers, and resorcinol-derived polymers.

3. The coating of claim 2, wherein the tyrosine-derived polyarylate comprises monomer units having the formula:

4. The coating of claim 2, wherein the linear polyesteramide comprises monomer units having the formula:

5. The coating of claim 2, wherein the dihydroxybenzoate polymer comprises monomer units having the formula:

6. The coating of claim 2, wherein the resorcinol-derived polymer comprises monomer units having the formula:

7. The coating of claim 1, wherein the polyethylene glycol is a poloxamer.

8. The coating of claim 1, wherein the polyethylene glycol comprises at least one terminal group blocked with a methyl ether.

9. The coating of claim 1, wherein the polyethylene glycol is a block copolymer comprising polyoxyethylene and polyoxypropylene units.

10. The coating of claim 3, wherein the tyrosine-derived polyarylate comprises a member of the P22 family.

11. The coating of claim 10, wherein the coating further comprises at least one antimicrobial ingredient.

12. The coating of claim 11, wherein the antimicrobial ingredient is selected from the group consisting of minocycline, rifampin, and mixtures thereof.

13. The coating of claim 12, wherein the PEG is PEG-400.

14. The coating of claim 10, wherein the tyrosine-derived polyarylate has a percentage of free acid ranging from about 10% to about 30%.

15. The coating of claim 11, wherein the percentage of free acid is about 27.5%.

16. The coating of claim 1, further comprising about 20% to about 70% of at least one drug, based on the combined weight of the drug, polyethylene glycol and polyphenolic polymer.

17. The coating of claim 16, wherein the at least one drug is selected from the group consisting of antimicrobial agents, anesthetics, analgesics, anti-inflammatory agents, anti-scarring agents, anti-fibrotic agents and leukotriene inhibitors.

18. The coating of claim 17, wherein the at least one drug is an antimicrobial agent selected from the group consisting of antibiotics, antiseptics, and disinfectants.

19. The coating of claim 17, wherein the at least one drug is an antibiotic selected from the group consisting of rifampin, minocycline, silver/chlorhexidine, and combinations thereof.

20. The coating of claim 19, wherein the antibiotic comprises rifampin and minocycline.

21. A medical device comprising the coating of claim 1.

22. The medical device of claim 21, wherein the medical device is comprised of a material selected from the group consisting of a metal, an organic material, a natural or synthetic polymer or copolymer, and a material of biological origin.

23. The medical device of claim 21, wherein a thickness of the coating ranges from 10 μ

m to about 250 μ

m.

24. The medical device of claim 21, wherein a thickness of the coating ranges from 15 μ

m to about 125 μ

m.

27. The coating of claim 1, wherein the polyethylene glycol is unmodified.

25. A coating comprising about 10% to about 20% polyethylene glycol and about 80% to about 90% of at least one polyphenolic polymer based on the combined weight of the polyethylene glycol and polyphenolic polymer, wherein the polyethylene glycol is selected from the group consisting of PEG-3350, PEG-1000, and PEG-400.

26. The coating of claim 25, further comprising at least one drug.

28. A coating comprising polyethylene glycol and at least one polyphenolic polymer comprising tyrosine-derived polyarylates.

29. The coating of claim 28, wherein the tyrosine-derived polyarylate comprises monomer units having the formula:

30. The coating of claim 28, wherein the polyethylene glycol is unmodified.

31. The coating of claim 28, wherein the polyethylene glycol is PEG-1000.

32. The coating of claim 28, wherein the polyethylene glycol comprises at least one terminal functional group comprising an ether.

33. The coating of claim 28, wherein the polyethylene glycol comprises nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene.

34. The coating of claim 28, wherein the polyethylene glycol comprises block copolymers based on ethylene oxide.

35. The coating of claim 28, wherein the polyethylene glycol comprises block copolymers based on propylene oxide.

36. The coating of claim 28, wherein the polyethylene glycol is PEG diacid.

37. The coating of claim 28, wherein the at least one polyphenolic polymer is P22-27.5.

38. The coating of claim 28, wherein the polyethylene glycol comprises 0.1 to 25% by weight, based on the combined weight of the at least one polyphenolic polymer and the polyethylene glycol.

39. The coating of claim 28, wherein the polyethylene glycol comprises 10 to 18% by weight, based on the combined weight of the at least one polyphenolic polymer and the polyethylene glycol.

40. The coating of claim 28, wherein the polyethylene glycol is a Pluronic copolymer.

41. The coating of claim 40, wherein the Pluronic copolymer is L44.