Drug delivery from stents

• US 8,753,659 B2
• Filed: 05/20/2013
• Issued: 06/17/2014
• Est. Priority Date: 01/11/2001
• Status: Expired due to Fees

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Lewis, Andrew L., Stratford, Peter W., Driver, Michael J.
• Primary Examiner(s): BARHAM, BETHANY P
• Application Number:
  US13/898,360
• Publication Number:
  US 20130309289A1
• Time in Patent Office: 393 Days
• Field of Search: None
• US Class Current: 424/422
• 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: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/434 of enzymes
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• 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: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C08L 101/02 characterised by the presence of specified groups , e.g. terminal or pendant functional groups
• CPC Class Codes: Y10T 29/49885 with coating before or during assembling

Abstract

An intravascular stent has a coating comprising a crosslinked amphiphilic polymer and a sparingly water soluble matrix metalloproteinase inhibitor (MMPI). Preferably the polymer is formed from 2-methacryloyloxy-2′-ethyltrimethylammonium phosphate inner salt, C_4-18 alkyl methacrylate and reactive and/or crosslinking monomer and the MMPI is a hydroxamic acid, more preferably batimastat. Preclinical and clinical results are reported, showing good luminal areas and reduced intimal thickening.

Claims

1. An intravascular stent comprising a metal body having a coating comprising a polymer and a restenosis inhibiting agent, wherein:

the restenosis inhibiting agent is a sparingly water soluble matrix metallo-proteinase inhibitor (MMPI); and

the polymer is a cross-linked amphiphilic polymer formed from a cross-linkable polymer of formula;

2. The stent according to claim 1 in which on at least the outer wall of the stent the coating comprises a layer of the amphiphilic polymer in which the MMPI is absorbed.

3. The stent according to claim 1 in which the polymer in the coating when swollen with water containing pyrene has hydrophobic domains observable by an I3:

I1 ratio of more than 0.8.

4. The stent according to claim 1 in which on at least an outer wall of the stent the coating comprises an inner layer of the amphiphilic polymer, and, adhered to the inner layer, the crystalline MMPI.

5. The stent according to claim 1, wherein X has a formula V:

6. The stent according to claim 5, wherein:

X³ and X⁴ are —

O—

; and

the group linking the anionic and cationic moieties is a C_1-12-alkanediyl group.

7. The stent according to claim 1, wherein X has a formula V:

8. The stent according to claim 7, wherein W¹ is C₂-C₆ alkanediyl and the aryl group is phenyl.

9. The stent according to claim 7, wherein W¹ is ethane-1,2-diyl.

10. The stent according to claim 1, wherein X is of formula VI:

11. The stent according to claim 10, wherein the groups R¹² are the same.

12. The stent according to claim 10, wherein the groups R¹² are methyl.

13. The stent according to claim 1, wherein R¹³ is a straight alkyl having 4 to 18 carbon atoms.

14. The stent according to claim 1, wherein R²⁰ comprises a silane group containing at least one substituent selected from halogen atoms and C_1-4-alkoxy groups.

15. The stent according to claim 1, wherein B and B² are independently straight chain C_2-8-alkanediyl.

16. The stent according to claim 1, wherein the MMPI is batimastat or marimastat.

17. The stent according to claim 1, wherein the MMPI is present in an amount in the range of 1 μ

g to 1000 μ

g per stent.