Drug delivery from stents

• US 8,465,758 B2
• Filed: 05/04/2010
• Issued: 06/18/2013
• 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:
  US12/773,677
• Publication Number:
  US 20100275431A1
• Time in Patent Office: 1,141 Days
• 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

A method of producing an intravascular stent has a coat 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. A method for producing a drug coated intravascular stent comprising the steps:

a) coating a metallic stent body on its inner and outer walls with a cross-linkable amphiphilic polymer;

b) subjecting the cross-linkable amphiphilic polymer to conditions under which cross-linking takes place to produce a polymer-coated stent;

c) contacting at least the outer coated wall of the polymer coated stent with a liquid drug composition comprising a sparingly water-soluble matrix metalloproteinase inhibitor (MMPI) and an organic solvent in which the MMPI is at least partially dissolved and which is capable of swelling the cross-linked polymer of the coating, for a time sufficient to swell the polymer coating on the outer wall, to produce a wet drug-coated stent; and

d) evaporating the organic solvent from the wet drug-coated stent to produce a dry drug-coated stent;

wherein the cross-linkable amphiphilic polymer is of formula;

2. The method according to claim 1 in which, in step c), the MMPI is both absorbed into the polymer and adsorbed at the surface of the polymer coating, whereby, upon evaporation of the solvent in step d), crystals of the MMPI are formed which are adherent to the surface of the dry drug-coated stent.

3. The method according to claim 1 in which, in step c) the contacting is by dipping the polymer coated stent in the liquid drug composition, optionally repeatedly dipping.

4. The method according to claim 1 in which in step c) the contacting is by flowing, spraying or dripping the liquid drug composition onto the stent, and immediately allowing evaporation of the solvent from the wet drug-coated stent in step d).

5. The method according to claim 1 in which the stent is, between steps b) and c), mounted onto the stent delivery section of a stent-delivery catheter, whereby the stent delivery section is also contacted with the liquid drug composition.

6. The method according to claim 5 wherein the stent-delivery catheter is a balloon catheter in which the balloon is formed of polyamide, and wherein the organic solvent in the liquid drug composition is selected from dimethylsulphoxide, dichloromethane, C_1-4 alcohol, and admixtures thereof.

7. The method according to claim 1, wherein the MMPI is present in an amount in the range 1 μ

g to 1000 μ

g per stent.

8. The method according to claim 1, wherein the MMPI is present in an amount in the range 10 μ

g to 150 μ

g per stent.

9. The method according to claim 1, wherein the MMPI is batimastat or marimastat.