Barriers for polymer-coated implantable medical devices and methods for making the same

• US 6,716,444 B1
• Filed: 09/28/2000
• Issued: 04/06/2004
• Est. Priority Date: 09/28/2000
• Status: Expired due to Term

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Castro, Daniel, Pacetti, Stephen D.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): EVANS, CHARESSE L
• Application Number:
  US09/676,049
• Time in Patent Office: 1,286 Days
• Field of Search: 424/400, 424/422, 424/423, 424/424, 424/426
• US Class Current: 424/422
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/306 Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/088 Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• 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

A drug eluting medical device is disclosed. The device includes a barrier layer for reducing the rate of release of a drug.

Claims

1. An implantable medical device comprising:

a substrate;

a barrier coating containing a drug said polymer disposed on said substrate; and

a barrier overlaying at least a portion of said coating, wherein said barrier comprises an inorganic material and is adapted to reduce a rate of release of said drug from said coating after insertion of said device into a body of a patient.

2. The implantable medical device of claim 1, wherein said barrier has a thickness ranging from about 50 angstroms to about 20,000 angstroms.

3. The implantable medical device of claim 1, wherein said barrier has a thickness ranging from about 100 angstroms to about 5,000 angstroms.

4. The implantable medical device of claim 1, wherein said barrier is a homogeneous layer.

5. The implantable medical device of claim 1, wherein said barrier comprises a plurality of discrete deposits.

6. The implantable medical device of claim 1, wherein said barrier is intermixed with an outer portion of said coating.

7. The implantable medical device of claim 1, wherein said inorganic material is selected from the group consisting of silicides of:

niobium, tantalum, titanium, tungsten, vanadium, and zirconium.

8. The implantable medical device of claim 1, wherein said inorganic material is selected from the group consisting of oxides of:

aluminum, barium, calcium, hafnium, niobium, silicon, tantalum, titanium, tungsten, and zirconium.

9. The implantable medical device of claim 1, wherein said inorganic material is selected from the group consisting of nitrides of:

chromium, silicon, titanium, and zirconium.

10. The implantable medical device of claim 1, wherein said inorganic material is a metal selected from the group consisting of aluminum, chromium, gold, hafnium, iridium, niobium, palladium, platinum, tantalum, titanium, tungsten, zirconium, and alloys thereof.

11. The implantable medical device of claim 1, wherein said drug is selected from the group consisting of antineoplastic, anti-inflammatory, antiplatelet, anticoagulant, fibrinolytic, thrombin inhibitor, antimitotic, antiallergic, and antiproliferative substances.

12. The implantable medical device of claim 1, wherein said drug is selected from the group consisting of paclitaxel, docetaxel, methotrexate, sodium heparin, hirudin, estradiol, actinomycin D, angiopeptin, captopril, nitroprusside, and nitric oxide.

13. The implantable medical device of claim 1, wherein said drug is selected from the group consisting of azathioprine, vincristine, vinblastine, agratroban, forskolin, vapiprost, mitomycin, cilazipril, lisinopril, phosphodiesterase inhibitors, and trizaolopyrimidine.

14. The implantable medical device of claim 1, wherein said device is a stent.

15. The implantable medical device of claim 1, wherein said device is a graft.

16. An implantable medical device comprising:

a substrate;

a polymer coating containing a drug said polymer disposed on said substrate; and

a barrier overlaying at least a portion of said coating, wherein said barrier comprises an inorganic material and is adapted to reduce a rate of release of said drug from said coating after insertion of said device into a body of a patient, wherein said inorganic material is selected from the group consisting of carbides of silicon, carbides of titanium, molybdenum disulfide, amorphous diamond, diamondlike carbon, pyrolytic carbon, ultra low temperature isotropic carbon, amorphous carbon, strontium titanate, and barium titanate.

17. An implantable medical device comprising:

a substrate;

a polymer coating containing a drug said polymer disposed on said substrate; and

a barrier overlaying at least a portion of said coating, said drug having significantly lower diffusivity in said barrier than in said coating.

18. An implantable medical device comprising:

a substrate;

a polymer coating containing a drug said polymer disposed on said substrate; and

a barrier overlaying at least a portion of said coating, said drug having significantly lower degree of solubility in said barrier than in said coating.

19. A method for making an implantable medical device, the method comprising:

forming a first layer comprising a polymer and a drug on said device; and

forming a barrier over at least a portion of said first layer, wherein said barrier comprises an inorganic material and is adapted to reduce a rate of release of said drug from said first layer after insertion of said device into a body of a patient.

20. The method of claim 19, wherein said barrier is applied by a process selected from the group consisting of plasma enhanced chemical vapor deposition, cathodic are physical vapor deposition, sputtering, reactive sputtering, thermal evaporation, electron beam evaporation, electroless plating, ion plating, thermal spraying, and ion beam deposition.

21. A method for making an implantable medical device, the method comprising:

forming a first layer comprising a polymer and a drug on said device; and

forming a barrier over at least a portion of said first layer, wherein said barrier comprises an inorganic material and is adapted to reduce a rate of release of said drug from said first layer after insertion of said device into a body of a patient, wherein said barrier is formed by a process selected from the group consisting of ion implantation, plasma ion implantation, alkoxide hydrolysis, and electroless plating.

22. A stent comprising a polymeric coating impregnated with a therapeutic substance for the sustained release of said therapeutic substance and a film layer covering said coating wherein said film layer includes fractured regions extending along the thickness of said film layer for allowing said therapeutic substance to be transmitted through said film layer.

23. The stent of claim 22, wherein said film layer is made of an inorganic compound.

24. A stent comprising a coating containing a therapeutic substance for the sustained release of said therapeutic substance and a film layer covering said coating wherein said film layer includes fractured regions extending along the thickness of said film layer for allowing said therapeutic substance to be transmitted through said film layer, wherein said film layer is made from SiOx.

25. A stent comprising a reservoir layer containing a therapeutic substance and deposits implanted into the surface of said reservoir layer and penetrating at least partially into said reservoir layer to reduce the rate of release of said therapeutic substance from said reservoir layer.

26. The stent of claim 25, wherein said deposits are made from an inorganic material.

27. The stent of claim 25, wherein said therapeutic substance is not capable of significantly or completely penetrating into said deposits such that said deposits reduce the rate of release of said therapeutic substance by changing the path of diffusion of said therapeutic substance from said reservoir layer to a direction which is different than the direction of release if said deposits were not present in said reservoir layer.

28. The stent of claim 25, wherein said deposits reduce the area normal to the direction at which diffusion of said therapeutic substance can occur.

29. A stent comprising a polymeric reservoir layer impregnated with a therapeutic substance and an intermittent pattern of a barrier layer disposed on said reservoir layer for reducing the rate of release of a therapeutic substance from said reservoir layer.

30. The stent of claim 29, wherein said barrier layer is made from an inorganic substance.

31. The stent of claim 29, wherein said barrier layer is impermeable to the diffusion of said therapeutic substance into said barrier layer such that said therapeutic substance diffuses out of said reservoir layer from the regions not covered by said barrier layer.

32. A method of manufacturing a drug eluting stent, comprising:

forming a reservoir layer containing a drug on a stent;

forming a barrier layer on said reservoir layer; and

patterning said barrier layer by removing portions of said barrier layer to expose areas of said reservoir layer.

33. The method of claim 32, wherein said barrier layer is made from an inorganic material.

34. The method of claim 32, wherein said barrier layer is made from a metallic material.

35. The method of claim 32, wherein said barrier layer is impermeable to the infusion of said drug into said barrier layer such that said drug is released from said reservoir layer from the areas that are not covered by said barrier layer.

36. The method of claim 32, wherein said removing portions of said barrier layer is conducted by a chemical etchant or laser treatment.

37. A method of modifying a coating for an implantable device to change the release profile of a therapeutic substance contained in said coating, comprising implanting deposits in the surface of said coating such that said deposits penetrate at least partially within said coating to modify the release profile of said therapeutic substance from said coating subsequent to the implantation of said device in a patient.

38. The method of claim 37, wherein said deposits are made from inorganic material.

39. The method of claim 37, wherein the rate of diffusion of said therapeutic substance is slower from said deposits than said coating.

40. The method of claim 37, wherein said deposits are made from a material which is impermeable to said therapeutic substance.

41. The method of claim 37, wherein said therapeutic substance has a lower degree of solubility when mixed in a material of said deposits than in a material of said coating.

42. A stent comprising a first layer containing a therapeutic substance and a second layer disposed over at least a portion of said first layer for reducing the rate of release of said therapeutic substance from said stent, wherein said second layer includes an inorganic substance.

43. The stent of claim 42, wherein said first layer includes a polymer.

44. A method of producing a drug eluting stent, comprising forming a first layer including a drug and forming a second layer over at least a portion of said first layer for reducing the rate of release of said drug from said stent, wherein said second layer includes an inorganic substance.

45. An implantable medical device comprising:

a substrate; and

a coating supported by the substrate, wherein the coating includes a polymer, a drug and an inorganic component.

46. The device of claim 45, wherein the inorganic component is intermixed with the polymer.

47. An implantable medical device, comprising:

a substrate;

a polymeric coating impregnated with a drug said polymeric coating supported by the substrate; and

a deposit intermixed with the polymeric coating such that the drug has a lower diffusivity rate through the deposit than the polymeric coating.

48. The device of claim 47, wherein the deposit is an inorganic compound.

49. An implantable medical device, comprising:

a substrate;

a polymeric coating impregnated with a drug said polymeric coating supported by the substrate; and

a deposit intermixed with the polymeric coating, wherein the deposit is completely or substantially impermeable to the drug.

50. An implantable medical device, comprising:

a substrate;

a polymeric coating impregnated with a drug said polymeric coating supported by the substrate; and

a deposit intermixed with the polymeric coating, wherein the drug is completely or substantially insoluble if mixed with the deposit.

51. An implantable medical device, comprising:

a substrate;

a polymeric coating impregnated with a drug said polymeric coating supported by the substrate; and

a deposit intermixed with the polymeric coating, wherein the drug is less soluble in the deposit than in the polymer of the coating.