Stents having bioabsorbable layers

• US 9,789,233 B2
• Filed: 04/17/2009
• Issued: 10/17/2017
• Est. Priority Date: 04/17/2008
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Douglas
• Primary Examiner(s): Sharma, Yashita
• Application Number:
  US12/426,198
• Publication Number:
  US 20090292351A1
• Time in Patent Office: 3,105 Days
• Field of Search: 623 11- 146, 424423
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0035 differing in release or diffusion time
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

Provided herein is a device comprising: a. stent; b. a plurality of layers on said stent framework to form said device; 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 device comprising:

a. a stent consisting essentially of layers of polymer and layers of pharmaceutical agent;

b. a plurality of layers deposited directly on said stent;

wherein at least one of said polymer layers comprises a bioabsorbable polymer and at least one of said pharmaceutical agent layers comprises a pharmaceutical agent selected from rapamycin, a prodrug, a derivative, an analog, a hydrate, an ester, and a salt thereof in intimate contact with said bioabsorbable polymer, wherein at least a portion of the pharmaceutical agent is in crystalline form, wherein said device provides an in vitro elution profile in which 5% to 25% of the pharmaceutical agent is eluted one day after the device is contacted with elution media.

2. The device of claim 1, wherein said device has a pharmaceutical agent content of about 1 μ

g/mm to about 15 μ

m/mm.

3. The device of claim 1, wherein said at least one of said polymer layers comprises a plurality of layers comprising a first polymer layer comprising a first bioabsorbable polymer and a second polymer layer comprising a second bioabsorbable polymer, wherein said at least one of said pharmaceutical agent layers is between said first polymer layer and said second polymer layer.

4. The device of claim 3, wherein said first and second bioabsorbable polymers are the same polymer.

5. The device of claim 3, wherein said first and second bioabsorbable polymers are different polymers.

6. The device of claim 3, wherein said second polymer layer has at least one contact point with at least one particle of said pharmaceutical agent in said pharmaceutical agent layer and said second polymer layer has at least one contact point with said first polymer layer.

7. The device of claim 3, wherein said stent has a stent longitudinal axis;

and said second polymer layer has a second polymer layer portion along said stent longitudinal axis wherein said second polymer layer portion is free of contact with particles of said pharmaceutical agent.

8. The device of claim 7, wherein said device has at least one pharmaceutical agent layer defined by a three-dimensional physical space occupied by crystal particles of said pharmaceutical agent and said three dimensional physical space is free of polymer.

9. The device of claim 7, wherein said stent comprises at least one strut having a strut length along said stent longitudinal axis, wherein said second polymer layer portion extends substantially along said strut length.

10. The device of claim 7, wherein said stent has a stent length along said stent longitudinal axis and said second polymer layer portion extends substantially along said stent length.

11. The device of claim 7, wherein said stent comprises at least five struts, each strut having a strut length along said stent longitudinal axis, wherein said second polymer layer portion extends substantially along the strut length of at least two struts.

12. The device of claim 7, wherein said stent comprises at least five struts, each strut having a strut length along said stent longitudinal axis, wherein said second polymer layer portion extends substantially along the strut length of at least three struts.

13. The device of claim 7, wherein said stent comprises at least five struts, each strut having a strut length along said stent longitudinal axis, wherein said second polymer layer portion extends substantially along the strut length of least four struts.

14. The device of claim 7, wherein said stent comprises at least five struts, each strut having a strut length along said stent longitudinal axis, wherein said second polymer layer portion extends substantially along the strut length of all said at least five struts.

15. The device of claim 7, wherein said stent has a stent length along said stent longitudinal axis and said second polymer layer portion extends along at least 50% of said stent length.

16. The device of claim 7, wherein said stent has a stent length along said stent longitudinal axis and said second polymer layer portion extends along at least 75% of said stent length.

18. The device of claim 1, wherein 5% to 25% of the first pharmaceutical agent is eluted one day after the device is contacted with elution media.

19. The device of claim 1, wherein 15% to 45% of the first pharmaceutical agent is eluted 7 days after the device is contacted with elution media.

20. The device of claim 1, wherein 25% to 60% of the first pharmaceutical agent is eluted 14 days after the device is contacted with elution media.

21. The device of claim 1, wherein 35% to 70% of the first pharmaceutical agent is eluted 21 days after the device is contacted with elution media.

17. A device comprising:

a. a stent consisting essentially of layers of polymer and layers of pharmaceutical agent;

b. a plurality of layers deposited directly on said stent, wherein a first layer comprises a first bioabsorbable polymer, a second layer comprises a layer of a first pharmaceutical agent, a third layer comprises a second bioabsorbable polymer, a fourth layer comprises a layer of said first pharmaceutical agent, and a fifth layer comprises a third bioabsorbable polymer,

wherein the first pharmaceutical agent is selected from rapamycin, a prodrug, a derivative, an analog, a hydrate, an ester, and a salt thereof, and wherein said device has a first pharmaceutical agent content of about 1 μ

g/mm to about 15 μ

g/mm, and

wherein at least a portion of the first pharmaceutical agent is in crystalline form.

22. A device comprising:

a. a stent consisting essentially of layers of polymer and layers of pharmaceutical agent;

b. a plurality of layers on said stent;

wherein at least one of said polymer layers comprises a solvent free bioabsorbable polymer and at least one of said pharmaceutical agent layers comprises a pharmaceutical agent selected from rapamycin, a prodrug, a derivative, an analog, a hydrate, an ester, and a salt thereof in intimate contact with said solvent free bioabsorbable polymer, wherein at least a portion of the pharmaceutical agent is in crystalline form,

wherein said device provides an in vitro elution profile in which

5% to 25% of the pharmaceutical agent is eluted one day after the device is contacted with elution media;

15% to 45% of the pharmaceutical agent is eluted 7 days after the device is contacted with elution media;

25% to 60% of the pharmaceutical agent is eluted 14 days after the device is contacted with elution media;

35% to 70% of the pharmaceutical agent is eluted 21 days after the device is contacted with elution media; and

40% to 100% of the pharmaceutical agent is eluted 28 days after the device is contacted with elution media.