Stents with ceramic drug reservoir layer and methods of making and using the same

• US 8,067,054 B2
• Filed: 04/05/2007
• Issued: 11/29/2011
• Est. Priority Date: 04/05/2007
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Weber, Jan
• Primary Examiner(s): Yuan; Dah-Wei
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US11/697,079
• Publication Number:
  US 20080249615A1
• Time in Patent Office: 1,699 Days
• Field of Search: 427/189, 427/2.24, 427/2.28, 427/2.1, 427/553, 427/554, 427/555, 427/556, 427/307, 427/256, 427/287, 427/2.3, 427/2.25, 427/230, 264/60, 428/472.1, 607/115, 606/191
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91575 connected peak to trough
• CPC Class Codes: A61F 2230/0054 V-shaped
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/088 Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/00 Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment

Abstract

A method of making a drug eluting stent comprises forming a porous stent body surface layer by ion implantation, applying a layer of ceramic particles on the porous layer and compressing the layer of ceramic particles. The layer of ceramic particles can be compressed to successively higher densities. Drugs can be loaded into the layer of ceramic materials at a relatively low density before the layer of ceramic materials is compressed to a higher density to achieve a desired low drug release rate.

Claims

1. A method of making a stent, the method comprising steps of:

implanting at least one type of ion into a metallic stent body material in at least one surface portion of the stent body material to produce at least one porous layer at the surface portion, the at least one porous layer comprising a plurality of open pores with a first average size for at least 50 volume percent of the open pores;

depositing a layer of ceramic particles on the porous layer, the ceramic particles having a second average size for at least 50 volume percent of the ceramic particles, the second average size being smaller than one tenth of the first average size; and

compressing the layer of ceramic particles to form a plurality of protuberances and/or recesses on a surface of the layer of ceramic particles, wherein compressing the layer of ceramic particles comprises compressing using a solid surface having a plurality of protuberances and/ or recesses.

2. The method of claim 1, wherein the step of depositing a layer of ceramic particles comprises applying at least one suspension of the ceramic particles and drying the applied suspension.

3. The method of claim 2, wherein the step of depositing a layer of ceramic particles comprises successively applying a plurality of stacked coatings of ceramic particles, wherein applying each of the plurality of the coatings comprises

applying at least one suspension of ceramic particles and drying the applied suspension.

4. The method of claim 1, wherein the step of implanting at least one type of ion comprises implanting ions of at least one element with a sufficiently high flux to produce concentrations of the element in the stent body material in excess of a solubility limit of the element in the stent body material.

5. The method of claim 1, wherein the step of implanting at least one type of ions comprises implanting at least one of argon, helium, xenon, oxygen and nitrogen into the stent body material.

6. The method of claim 5, wherein the step of implanting at least one type of ions comprises implanting at least argon into a stainless steel portion of the stent body material.

7. The method of claim 1, wherein the step of implanting at least one type of ions comprises implanting ions of a first type to produce a porous layer, and implanting ions of a second type to produce a porous structure within the porous layer.

8. The method of claim 7, wherein the step of implanting ions of a first type comprises implanting ions of the first type to produce a first plurality of open pores with a first average pore size for at least 50 volume percent of the first plurality of open pores, and implanting ions of a second type comprises implanting ions of the second type to produce a second plurality of open pores with a second average pore size for at least 50 volume percent of the second plurality of open pores.

9. The method of claim 1, further comprising loading at least one drug into the layer of ceramic particles.

10. The method of claim 9, wherein the step of compressing the layer of ceramic particles comprises compressing the layer to a first density and further compressing the layer to a second density, and wherein loading at least one drug comprises loading the drug into the layer while the layer is at the first density.

11. The method of claim 1, wherein the step of depositing a layer of ceramic particles on the porous layer comprises depositing the layer of ceramic particles on an abluminal surface of a tubular portion of the stent body material, the method further comprising supporting an adluminal surface portion of the tubular portion.

12. The method of claim 11, wherein the step of pressing the layer of ceramic particles with a solid surface comprises pressing the layer with a cylindrical arch section of a solid surface.

13. The method of claim 9, wherein the step of depositing a layer of ceramic particles comprises applying at least one suspension of the ceramic particles and drying the applied suspension, and wherein loading at least one drug into the layer of ceramic particles comprises incorporating the drug in the suspension.

14. The method claim 1, further comprising creating an opening through the metallic stent body material and the layer of ceramic particles by laser ablation after the implanting, depositing and compressing steps.

15. A method of making a stent, the method comprising steps of:

depositing a layer of ceramic particles on at least one surface portion of a stent body material;

compressing the layer of ceramic particles to a first density;

dispersing at least one drug into the layer of ceramic particles while the layer of ceramic particles is at the first density; and

compressing the layer of ceramic particle to a second density that is higher than the first density.

16. The method of claim 15, further comprising forming a porous surface layer on the at least one surface portion of the stent body material.

17. The method of claim 15, wherein the step of forming a porous surface layer comprises forming the porous surface layer by ion implantation.

22. The method of claim 16, wherein the porous layer comprises a plurality of open pores with a first average size for at least 50 volume percent of the open pores, and the ceramic particles have a second average size for at least 50 volume percent of the ceramic particles, the second average size being smaller than one tenth of the first average size.

18. A method of making a stent, the method comprising:

implanting at least one type of ions into a metallic stent body material in at least one surface portion of the stent body material to produce at least one porous layer at the surface portion, the at least one porous layer comprising a plurality of open pores with a first average size for at least 50 volume percent of the open pores;

depositing a layer of particles on the porous layer, the particles having a second average size for at least 50 volume percent of the particles, the second average size being smaller than one tenth of the first average size; and

compressing the layer of particles to form a plurality of protuberances and/or recesses on a surface of the layer of particles, wherein compressing the layer of particles comprises compressing using a solid surface having a plurality of protuberances and/or recesses.

19. The method of claim 18, wherein the step of depositing a layer of particles on the porous layer comprises depositing at least one type of metal, polymeric and ceramic particles.

20. A method of making a stent, the method comprising steps of:

implanting at least one type of ions into a metallic stent body material in at least one surface portion of the stent body material to produce at least one porous layer at the surface portion;

depositing a layer of particles on the at least one porous layer;

compressing the layer of particles to a first density;

dispersing at least one drug into the layer of particles while the layer of particles is at the first density; and

compressing the layer of particle to a second density that is higher than the first density.

21. The method of claim 20, wherein depositing a layer of particles on the porous layer comprises depositing at least one type of metal, polymeric and ceramic particles.

23. The method of claim 20, wherein the at least one porous layer comprises a plurality of open pores with a first average size for at least 50 volume percent of the open pores, and the particles have a second average size for at least 50 volume percent of the particles, the second average size being smaller than one tenth of the first average size.