Diffusion barrier layer for implantable devices

• US 6,663,662 B2
• Filed: 12/28/2000
• Issued: 12/16/2003
• Est. Priority Date: 12/28/2000
• Status: Expired due to Term

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D., Hossainy, Syed F. A.
• Primary Examiner(s): McDermott, Corrine
• Assistant Examiner(s): Phan, Hieu
• Application Number:
  US09/750,515
• Publication Number:
  US 20020123801A1
• Time in Patent Office: 1,083 Days
• Field of Search: 623/1.39, 623/1.4, 623/1.42, 623/1-3-
• US Class Current: 623/1.13
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2/89 the wire-like elements comprising two or more adjacent rings flexibly connected by separate members
• CPC Class Codes: A61F 2002/075 the stent being loosely attached to the graft material, e.g. by stitching

Abstract

A diffusion barrier for an implantable device, such as a stent, carrying a therapeutic or bioactive substance is disclosed. The diffusion barrier reduces the rate at which the therapeutic or bioactive substance is released from the device. The diffusion barrier can be made from a polymeric material impregnated with particles.

Claims

1. A stent, comprising a coating containing particles, wherein the particles are configured to remain in the coating during the release of an active ingredient to reduce a rate of release of the active ingredient from the coating after the stent is implanted in a passageway.

2. The stent of claim 1, wherein the stent comprises cavities containing the active ingredient for releasing the active ingredient when the stent is implanted in a passageway.

3. The stent of claim 1, wherein the coating is a first coating and the stent additionally comprises a second coating formed between the surface of the stent and the first coating, the second coating carrying the active ingredient for the release of the active ingredient when the stent is implanted in a passageway.

4. The stent of claim 1, wherein the coating is a first coating and the stent additionally comprises:

(a) a second coating formed on at least a portion of a surface of the stent; and

(b) a third coating formed on at least a portion of the second coating, the third coating carrying the active ingredient for the release of the active ingredient when the stent is implanted in a passageway,

wherein the second coating provides an adhesive tie between the surface of the stent and the third coating.

5. The stent of claim 1, wherein the active ingredient is for the treatment of restenosis.

6. The stent of claim 1, wherein the size of the particles is not greater than about 10% of the thickness of the coating.

7. The stent of claim 1, wherein the coating is made from an ethylene vinyl alcohol copolymer.

8. The stent of claim 1, wherein the particles are made from an inorganic material.

9. The stent of claim 1, wherein the particles are made from a material selected from a group of metals, metal oxides, carbonaceous compounds, main group oxides, nitrides, carbides, and calcium salts.

10. The stent of claim 1, wherein the particles are made from a material selected from a group of rutile titanium oxide, anatase titanium dioxide, niobium oxide, tantalum oxide, zirconium oxide, iridium oxide, tungsten oxide, silica, alumina, gold, hafnium, platinum, iridium, palladium, tungsten, tantalum, niobium, zirconium, titanium, aluminum, chromium, lampblack, furnace black, carbon black, fumed carbon black, gas black, channel black, activated charcoal, diamond, titanium nitride, chromium nitride, zirconium nitride, tungsten carbide, silicon carbide, titanium carbide, hydroxyapatite, dahlite, brushite, tricalcium phosphate, calcium sulphate, calcium carbonate, silicides, barium titanate, and strontium titanate.

11. The stent of claim 1, wherein the particles are made from a polymeric material selected from a group of polyolefins, polyurethanes, cellulosics, polyesters, polyamides, poly(hexamethylene isophthalamide/terephthalamide) poly(ethylene terephthalate-co-p-oxybenzoate), poly(hydroxy amide ethers), polyacrylates, polyacrylonitrile, acrylonitrile/styrene copolymer, rubber-modified acrylonitrile/acrylate copolymer, poly(methyl methacrylate), liquid crystal polymers, poly(phenylene sulfide), polystyrenes, polycarbonates, poly(vinyl alcohols), poly(ethylene-vinyl alcohol), epoxies composed of bisphenol A based diepoxides with amine cure, aliphatic polyketones, polysulfones, poly(ester-sulfone), poly(urethane-sulfone), poly(carbonate-sulfone), poly(3-hydroxyoxetane), poly(amino ethers), gelatin, amylose, parylene-C, parylene-D, parylene-N, and mixtures thereof.

12. The stent of claim 11, wherein the polyolefins are selected from a group of polyethylenes, poly(vinyl chloride), poly(vinylidene chloride), poly(vinyl fluoride), poly(vinylidene fluoride), poly(tetrafluoroethylene), poly(chlorotrifluoroethylene), and mixtures thereof.

13. The stent of claim 11, wherein the polyurethane has a glass transition temperature above a storage temperature.

14. The stent of claim 11, where in the polyurethane has a non-polar soft segment, the non-polar soft segment is selected from the group of hydrocarbons, silicones, fluorosilicones, and mixtures thereof.

15. The stent of claim 11, wherein the cellulosics are selected from the group of cellulose acetate having a DS greater than about 0.8, or less than about 0.6, ethyl cellulose, cellulose nitrate, cellulose acetate butyrate, methyl cellulose, and mixtures thereof.

16. The stent of claim 11, wherein the polyesters are selected from a group of poly(ethylene terephthalate), poly(ethylene 2,6-naphthalene dicarboxylate), poly (butylene terephthalate), and mixtures thereof.

17. The stent of claim 11, wherein the polyamides are selected from a group of nylon-6, nylon-6,6, nylon-6,9, nylon-6,10, aromatic nylon, and mixtures thereof.

18. The coating of claim 1, wherein the particles have a volume sufficient to reduce the area normal to the direction at which diffusion of the active ingredient occurs in the coating.

19. The coating of claim 1, wherein the particles are dispersed in the coating to increase the diffusion distance that the active ingredient must travel in the coating to be released from the coating.

20. The coating of claim 1, wherein the particles are capable of partially absorbing or attracting the active ingredient.

21. A coating for a prosthesis comprising an agent and inorganic particles for reducing the rate at which the agent travels through the coating subsequent to the implantation of the prosthesis in a human body.

22. The coating of claim 21, wherein the coating is made from a polymeric material.

23. The coating of claim 21, wherein the prosthesis is a stent.

24. The coating of claim 21, wherein the particles have a volume sufficient to reduce the area normal to the direction at which diffusion of the agent occurs in the coating.

25. The coating of claim 21, wherein the particles are dispersed in the coating to increase the diffusion distance that the agent must travel in the coating to be released from the coating.

26. The coating of claim 21, wherein the particles are capable of partially absorbing or attracting the agent.

27. A stent having a coating comprising:

a first region including a polymer containing an active ingredient; and

a second region overlaying at least a portion of the first region, wherein the second region comprises particles adapted to prolong the residence time of the active ingredient at the site of implantation of the stent.

28. The stent of claim 27, additionally comprising a third region devoid of any active ingredients disposed beneath the first region and the surface of the stent.

29. The stent of claim 27, wherein the thickness of the second region is about 0.1 microns to about 10 microns.

30. The stent of claim 27, wherein the size of the particles is less than or equal to about 10% of the thickness of the second region.

31. The stent of claim 27, wherein the particle fraction volume of the second region is greater than 0 and less than or equal to about 0.74.

32. A stent having a coating comprising:

(a) a first layer including at least one polymer and at least one active ingredient; and

(b) a barrier layer overlaying at least a portion of the first layer, the barrier layer comprising

(i) particles adapted to reduce the rate of release of the active ingredient from the first layer after insertion of the stent into a biological lumen, and

(ii) a first region and a second region, wherein the first region of the barrier layer has a greater particle volume fraction as compared to the second region of the barrier layer.

33. The stent of claim 32, wherein the particle volume fraction of the first region is less than or equal to 0.74.

34. The stent of claim 32, wherein the first region includes a first polymer and the second region includes a second polymer.

35. The stent of claim 32, wherein first layer further includes a first region disposed beneath the first region of the barrier layer and a second region disposed beneath the second region of the barrier layer, wherein each of the first and second regions of the first layer includes a different active ingredient.