COATED STENTS

• US 20100256748A1
• Filed: 03/31/2010
• Published: 10/07/2010
• Est. Priority Date: 04/01/2009
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Douglas
• Granted Patent: US 9,981,072 B2
• Time in Patent Office: Days
• US Class Current: 623/1.460
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Provided herein is a coated coronary stent, comprising: a. stent; b. a plurality of layers deposited on said stent to form said coronary stent; wherein at least one of said layers comprises a bioabsorbable polymer and at least one of said layers comprises one or more active agents; wherein at least part of the active agent is in crystalline form.

Claims

1. A coated stent, comprising

a. a stent comprising a plurality of stent struts each having an abluminal surface, a luminal surface, and two sidewall surfaces;

b. a coating comprising an active agent and a bioabsorbable polymer;

wherein a ratio of an abluminal coating thickness on the abluminal surface to a luminal coating thickness on the luminal surface is at most 90;

10.

2. The coated stent of claim 1, wherein the ratio of abluminal coating thickness to luminal coating thickness is at least one of:

at most 50;

50, at most 65;

35, at most 70;

30, and at most 80;

20.

3. The coated stent of claim 1, wherein the ratio of abluminal coating thickness to luminal coating thickness is achieved during coating of the stent with the coating without a masking element.

4. The coated stent of claim 1, wherein the ratio of abluminal coating thickness to luminal coating thickness is achieved during coating of the stent with the coating without shielding the luminal surfaces.

5. The coated stent of claim 1 wherein the ratio of abluminal coating thickness to luminal coating thickness is achieved during coating of the stent with the coating wherein the stent is in at least one of:

a collapsed condition, an expanded condition, and an intermediate condition.

6. The coated stent claim 1, wherein an average strut thickness of the stent when measured from the abluminal surface to the luminal surface is at least one of:

at most 140 microns, at most 125 microns, at most 100 microns, at most 90 microns, at most 80 microns, at most 75 microns, at most 65 microns, and at most 63 microns.

11. The coated stent of claim 1, wherein the coating contacts at least one of:

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99% of the abluminal, luminal, and sidewall surfaces of the struts of the stent.

12. The coated stent of claim 11, wherein contact of the coating to the stent surfaces is measured by scanning electron microscopy of at least one cross section of a strut of the stent.

13. The coated stent of claim 11, wherein contact of the coating is measured when the stent is at least one of:

in a collapsed condition, and in an expanded condition.

21. A method of preparing a coated stent of claim 1 comprising:

a. providing a stent;

b. depositing a coating comprising a plurality of layers on said stent;

wherein at least one of said layers comprises a pharmaceutical agent, wherein at least one of said layers comprises a polymer, and wherein at least a portion of the pharmaceutical agent is in crystalline form, and wherein the polymer comprises at least one of a bioabsorbable polymer, and a durable polymer.

22. The method claim 21, wherein the stent has a thickness of about 50% or less of a thickness of the coated stent.

23. The method claim 21, wherein the stent has a thickness of about 100 μ

m or less.

24. The method claim 21, wherein depositing a plurality of layers on said stent to form said coronary stent comprises depositing polymer particles on said stent in dry powder form.

7. A coated stent, comprising

a. a stent comprising a plurality of stent struts each having an abluminal surface, a luminal surface, and two sidewall surfaces;

b. a coating comprising an active agent and a polymer;

wherein the coating is substantially conformal to the abluminal, luminal, and sidewall surfaces of the struts of the stent.

8. The coated stent of claim 7, wherein the coating adheres to at least one of:

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99% of the abluminal, luminal, and sidewall surfaces of the struts of the stent.

9. The coated stent of claim 8, wherein adherence of the coating is measured by scanning electron microscopy of at least one cross section of a strut of the stent.

10. The coated stent of claim 8, wherein adherence of the coating is measured when the stent is at least one of:

in a collapsed condition, and in an expanded condition.

14. The coated stent of claim 7, wherein the polymer comprises at least one of:

a bioabsorbable polymer and a durable polymer.

15. The coated stent of claim 7, wherein the active agent comprises at least one of a pharmaceutical agent and a biological agent.

16. The coated stent of claim 7, wherein the active agent comprises a macrolide immunosuppressive (limus) drug.

17. The coated stent claim 7, wherein an average strut thickness of the stent when measured from the abluminal surface to the luminal surface is at least one of:

at most 140 microns, at most 125 microns, at most 100 microns, at most 90 microns, at most 80 microns, at most 75 microns, at most 65 microns, and at most 63 microns.

25. A method of preparing a coated stent of claim 7 comprising:

a. providing a stent;

b. depositing a coating comprising a plurality of layers on said stent;

wherein at least one of said layers comprises a pharmaceutical agent, wherein at least one of said layers comprises a polymer, and wherein at least a portion of the pharmaceutical agent is in crystalline form, and wherein the polymer comprises at least one of a bioabsorbable polymer, and a durable polymer.

18. A coated stent, comprising

a. a stent comprising a plurality of stent struts each having an abluminal surface, a luminal surface, and two sidewall surfaces;

b. a coating comprising an active agent and a bioabsorbable polymer;

wherein an abluminal coating thickness on the abluminal surface and a luminal coating thickness on the luminal surface are substantially the same.

19. The coated stent of claim 18, wherein the abluminal coating thickness is at least one of:

at most 10% greater than the luminal coating thickness, at most 20% greater than the luminal coating thickness, at most 30% greater than the luminal coating thickness, at most 50% greater than the luminal coating thickness.

20. The coated stent claim 18, wherein an average strut thickness of the stent when measured from the abluminal surface to the luminal surface is at least one of:

at most 140 microns, at most 125 microns, at most 100 microns, at most 90 microns, at most 80 microns, at most 75 microns, at most 65 microns, and at most 63 microns.

26. A method of preparing a coated stent of claim 18 comprising:

a. providing a stent;

b. depositing a coating comprising a plurality of layers on said stent;

wherein at least one of said layers comprises a pharmaceutical agent, wherein at least one of said layers comprises a polymer, and wherein at least a portion of the pharmaceutical agent is in crystalline form, and wherein the polymer comprises at least one of a bioabsorbable polymer, and a durable polymer.

27. A method of preparing a coated stent comprising:

a. providing a stent;

b. depositing a coating comprising a plurality of layers on said stent;

wherein at least one of said layers comprises at least one of a bioabsorbable polymer and a durable polymer;

wherein depositing the coating comprises depositing each layer by the following steps;

discharging at least one pharmaceutical agent and/or at least one active biological agent in dry powder form through a first orifice;

discharging the at least one polymer in dry powder form through said first orifice or through a second orifice;

depositing the polymer and pharmaceutical agent and/or active biological agent particles onto said stent, wherein an electrical potential is maintained between the stent and the polymer and pharmaceutical agent and/or active biological agent particles, thereby forming said layer; and

sintering said layer under conditions that do not substantially modify the morphology of said pharmaceutical agent and/or the activity of said biological agent,

wherein a ratio of an abluminal coating thickness on the abluminal surface to a luminal coating thickness on the luminal surface is at most 90;

10.

28. The method of claim 27, wherein the ratio of abluminal coating thickness to luminal coating thickness is at least one of:

at most 50;

50, at most 65;

35, at most 70;

30, and at most 80;

20.

29. The method of claim 27, wherein the ratio of abluminal coating thickness to luminal coating thickness is achieved during coating of the stent with the coating wherein the stent is in at least one of:

a collapsed condition, an expanded condition, and an intermediate condition.

30. The method of claim 27, wherein an average strut thickness of the stent when measured from the abluminal surface to the luminal surface is at least one of:

at most 140 microns, at most 125 microns, at most 100 microns, at most 90 microns, at most 80 microns, at most 75 microns, at most 65 microns, and at most 63 microns.

31. A method of preparing a coated stent comprising:

a. providing a stent;

b. depositing a coating comprising a plurality of layers on said stent;

wherein at least one of said layers comprises at least one of a bioabsorbable polymer and a durable polymer;

wherein depositing the coating comprises depositing each layer by the following steps;

discharging at least one pharmaceutical agent and/or at least one active biological agent in dry powder form through a first orifice;

discharging the at least one polymer in dry powder form through said first orifice or through a second orifice;

depositing the polymer and pharmaceutical agent and/or active biological agent particles onto said stent, wherein an electrical potential is maintained between the stent and the polymer and pharmaceutical agent and/or active biological agent particles, thereby forming said layer; and

sintering said layer under conditions that do not substantially modify the morphology of said pharmaceutical agent and/or the activity of said biological agent,

wherein the coating is substantially conformal to each of an abluminal, luminal, and sidewall surface of the struts of the stent.

32. The method of claim 31, wherein the coating adheres to at least one of:

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99% of the abluminal, luminal, and sidewall surfaces of the struts of the stent.

33. The method of claim 31, wherein the coating contacts at least one of:

at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99% of the abluminal, luminal, and sidewall surfaces of the struts of the stent.

34. A method of preparing a coated stent comprising:

a. providing a stent;

b. depositing a coating comprising a plurality of layers on said stent;

wherein at least one of said layers comprises at least one of a bioabsorbable polymer and a durable polymer;

wherein depositing the coating comprises depositing each layer by the following steps;

discharging at least one pharmaceutical agent and/or at least one active biological agent in dry powder form through a first orifice;

discharging the at least one polymer in dry powder form through said first orifice or through a second orifice;

depositing the polymer and pharmaceutical agent and/or active biological agent particles onto said stent, wherein an electrical potential is maintained between the stent and the polymer and pharmaceutical agent and/or active biological agent particles, thereby forming said layer; and

sintering said layer under conditions that do not substantially modify the morphology of said pharmaceutical agent and/or the activity of said biological agent,

wherein an abluminal coating thickness on the abluminal surface and a luminal coating thickness on the luminal surface are substantially the same.

35. The method of claim 34, wherein the abluminal coating thickness is at least one of:

at most 10% greater than the luminal coating thickness, at most 20% greater than the luminal coating thickness, at most 30% greater than the luminal coating thickness, at most 50% greater than the luminal coating thickness.

36. The method of claim 34, wherein an average strut thickness of the stent when measured from the abluminal surface to the luminal surface is at least one of:

at most 140 microns, at most 125 microns, at most 100 microns, at most 90 microns, at most 80 microns, at most 75 microns, at most 65 microns, and at most 63 microns.

37. A coated coronary stent, comprising:

a stent;

a first layer of bioabsorbable polymer; and

a coating comprising rapamycin and a second bioabsorbable polymer wherein at least part of rapamycin is in crystalline form and wherein the first polymer is a slow absorbing polymer and the second polymer is a fast absorbing polymer, and wherein at least one of;

the coating is substantially conformal to each of an abluminal, luminal, and sidewall surface of the struts of the stent,

an abluminal coating thickness on the abluminal surface and a luminal coating thickness on the luminal surface are substantially the same, and

a ratio of an abluminal coating thickness on the abluminal surface to a luminal coating thickness on the luminal surface is at most 90;

10.

38. The stent of claim 37 wherein the fast absorbing polymer is PLGA copolymer with a ratio of about 40:

60 l-lactide;

glycolide to about 60;

40 l-lactide;

glycolide and the slow absorbing polymer is a PLGA copolymer with a ration of about 70;

30 l-lactide;

glycolide to about 90;

10 l-lactide;

glycolide.