Stent coatings comprising hydrophilic additives

• US 7,279,174 B2
• Filed: 05/08/2003
• Issued: 10/09/2007
• Est. Priority Date: 05/08/2003
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Tang, Yiwen, Pacetti, Stephen D.
• Primary Examiner(s): Kennedy; Sharon E.
• Application Number:
  US10/431,711
• Publication Number:
  US 20040224001A1
• Time in Patent Office: 1,615 Days
• Field of Search: 424/422, 623/1.42
• US Class Current: 424/422
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08L 2666/04 Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 2666/22 Macromolecular compounds not provided for in C08L2666/16 - C08L2666/20
• CPC Class Codes: C08L 33/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: C08L 75/04 Polyurethanes
• CPC Class Codes: C09D 133/08 Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C09D 133/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C09D 133/12 Homopolymers or copolymers of methyl methacrylate

Abstract

A coating for implantable medical devices and a method for fabricating thereof are disclosed. The coating includes a mixture of a hydrophobic polymer and a polymeric hydrophilic additive, wherein the hydrophobic polymer and the hydrophilic additive form a physically entangled or interpenetrating system.

Claims

1. An implantable medical device comprising a coating, the coating including

a mixture of at least one poly(meth)acrylate comprising a macromolecular chain and at least one polyalkylene glycol comprising a macromolecular chain,

wherein a physically entangled or interpenetrating system formed of the macromolecular chains of the poly(meth)acrylate and the polyalkylene glycol,

wherein the poly(meth)acrylate has a number average molecular weight (M_n) between about 50,000 and about 1,000,000 Daltons, and

wherein the polyalkylene glycol has a M_n between about 5,000 and about 100,000 Daltons.

2. The device of claim 1, wherein the device is a stent.

3. The device of claim 1, wherein a ratio between the poly(meth)acrylate and the polyalkylene glycol is between about 99:

1 and about 9;

1.

4. The device of claim 1, wherein the poly(meth)acrylate is selected from a group consisting of poly(methyl methacrylate), poly(ethyl methacrylate), poly(n-propyl methacrylate), poly(iso-propyl methacrylate), poly(n-butyl methacrylate), poly(iso-butyl methacrylate), poly(tert-butyl methacrylate), poly(methyl acrylate), poly(ethyl acrylate), poly(n-propyl acrylate), poly(iso-propyl acrylate), poly(n-butyl acrylate), poly(iso-butyl acrylate), and mixtures thereof.

5. The device of claim 1, wherein the polyalkylene glycol is selected from a group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(ethylene oxide-co-propylene oxide), poly(trimethylene glycol), poly(tetramethylene glycol), and mixtures thereof.

6. The device of claim 1, wherein the coating additionally comprises a drug.

7. The device of claim 6, wherein the drug is selected from a group consisting of rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, and combinations thereof.

8. An implantable medical device comprising a coating, the coating including a mixture of at least one hydrophobic polymer comprising a macromolecular chain and at least one polymeric hydrophilic polymer comprising a macromolecular chain,

wherein a physically entangled or interpenetrating system formed of the macromolecular chains of the hydrophobic polymer and the hydrophilic polymer,

wherein the hydrophobic polymer has a number average molecular weight (M_n) between about 50,000 and about 1,000,000 Daltons, and

wherein the hydrophilic polymer has a M_n between about 5,000 and about 100,000 Daltons.

9. The device of claim 8, wherein the device is a stent.

10. The device of claim 8, wherein the hydrophobic polymer has a Hildebrand solubility parameter lower than about 10.7 (cal/cm³)^1/2.

11. The device of claim 8, wherein the hydrophobic polymer has an equilibrium water adsorption less than about 10 mass % at room temperature.

12. The device of claim 8, wherein the hydrophobic polymer comprises poly(meth)acrylates, vinyl polymers, polyolefins, halogenanated polymers, polymers having urethane groups, polybutyrals, nylon, silicones, polycarbonate, or polysulfone.

13. The device of claim 12, wherein the poly(meth)acrylates are selected from a group consisting of poly(methyl methacrylate), poly(ethyl methacrylate), poly(n-propyl methacrylate), poly(iso-propyl methacrylate), poly(n-butyl methacrylate), poly(iso-butyl methacrylate), poly(tert-butyl methacrylate), poly(methyl acrylate), poly(ethyl acrylate), poly(n-propyl acrylate), poly(iso-propyl acrylate), poly(n-butyl acrylate), poly(iso-butyl acrylate), and mixtures thereof.

14. The device of claim 12, wherein the vinyl polymers are selected from a group consisting of poly(ethylene-co-vinyl alcohol), poly(ethylene-co-vinyl acetate), poly(vinyl acetate), polystyrene, poly(styrene-co-iso-butylene), poly(styrene-co-ethylene-co-butylene-co-styrene) terpolymers, and poly(styrene-co-butadiene-co-styrene) terpolymers, and mixtures thereof.

15. The device of claim 12, wherein the halogenanated polymers are selected from a group consisting of poly(vinyl fluoride), poly(vinylidene fluoride), polyhexafluoropropene, poly(hexafluoropropene-co-vinylidene fluoride), poly(ethylene-co-hexafluoropropene), polytetrafluoroethylene, poly(vinyl chloride), poly(vinylidene chloride), and mixtures thereof.

16. The device of claim 12, wherein the polymers having urethane groups are selected from a group consisting of polyether urethanes, polyester urethanes, polyurethaneureas, polycarbonate urethanes, silicone urethanes, and mixtures thereof.

17. The device of claim 8, wherein the polymeric hydrophilic compound is selected from a group consisting of polyalkylene glycols, hyaluronic acid, chondroitan sulfate, chitosan, glucosaminoglucans, dextran, dextrin, dextran sulfate, cellulose acetate, carboxymethyl cellulose, hydroxyethyl cellulose, cellulosics, polypeptides, poly(2-hydroxyethyl methacrylate), polyacrylamide, polyacrylimide, poly(ethylene amine), poly(allyl amine), poly(vinyl pyrrolidone), poly(vinyl alcohol), poly(acrylic acid), poly(methacrylic acid), acrylic acid copolymers, methacrylic acid co-polymers, polyvinyl alkyl ethers, non-ionic tetrafunctional block-copolymer surfactants, gelatin, collagen, albumin, chitin, heparin, elastin, fibrin, and mixtures thereof.

18. The device of claim 17, wherein the polyalkylene glycols are selected from a group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(ethylene oxide-co-propylene oxide), poly(trimethylene glycol), poly(tetramethylene glycol), and mixtures thereof.

19. The device of claim 8, wherein the ratio between the hydrophobic polymer and the polymeric hydrophilic additive is between about 99:

1 and about 9;

1.

20. The device of claim 8, wherein the coating additionally comprises a drug.

21. The device of claim 20, wherein the drug is selected from a group consisting of rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin, 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, and combinations thereof.

22. An implantable medical device comprising a coating, the coating including a mixture of at least one hydrophobic polymer and at least one polymeric hydrophilic compound, wherein the macromolecular chains of the hydrophobic. polymer and the hydrophilic compound form a physically entangled or interpenetrating system, and

wherein the hydrophobic polymer comprises poly(meth)acrylates, vinyl polymers, atactic polypropylene, halogenanated polymers, polymers having urethane groups, polybutyrals, nylon, silicones, polycarbonate, or polysulfone.