Liquid and low melting coatings for stents

• US 8,900,618 B2
• Filed: 03/15/2013
• Issued: 12/02/2014
• Est. Priority Date: 10/22/2001
• Status: Expired due to Fees

• Current Assignee: Covidien LP (Medtronic Plc)
• Original Assignee: Covidien LP (Medtronic Plc)
• Inventors: Pathak, Chandrashekhar
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US13/835,370
• Publication Number:
  US 20140106060A1
• Time in Patent Office: 627 Days
• US Class Current: 424/425
• 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 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2230/0013 Horseshoe-shaped, e.g. crescent-shaped, C-shaped, U-shaped
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2/16 using chemical substances
• CPC Class Codes: A61L 2/28 Devices for testing the effectiveness or completeness of sterilisation, e.g. indicators which change colour apparatus involving enzymes or microorganisms C12M1/34; methods involving enzymes or microorganisms C12Q1/00
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 2420/04 Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/049 Rubbers
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/125 having a macromolecular matrix
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

Stents with coatings comprising a combination of a restenosis inhibitor comprising an HMG-CoA reductase inhibitor and a carrier. Also provided are methods of coating stents with a combination of an HMG-CoA reductase inhibitor and a carrier. A preferred example of a restenosis inhibitor is cerivastatin. The stent coatings have been shown to release restenosis inhibitors in their active forms.

Claims

1. A method of coating a stent comprising:

providing a stent;

providing a coating composition comprising an HMG-CoA reductase inhibitor in an amount of about 1 to 50 wt. %, and a polymeric biodegradable carrier component comprising a polymer selected from polycaprolactone, ethylene-vinyl acetate polymer, and a two-part silicone rubber;

expanding the stent to an increased diameter; and

applying the coating composition to the stent,

wherein the HMG-CoA reductase inhibitor is released from the stent at a rate of >

20 μ

g/ml per day.

2. The method of claim 1, wherein applying the coating composition comprises spraying or painting the coating composition onto the stent, or immersing the stent in the coating composition.

3. The method of claim 1, wherein the HMG-CoA reductase inhibitor is selected from cerivastatin, atorvastatin, simvastatin, fluvastatin, lovastatin, and pravastatin.

4. The method of claim 1, wherein the HMG-CoA reductase inhibitor comprises cerivastatin.

5. The method of claim 1, wherein the coating composition further comprises one or more bioactive compounds selected from the group consisting of paclitaxel, paclitaxel analogs, actinomycin D, actinomycin D analogs, rapamycin, rapamycin analogs, and mixtures thereof.

6. A method of coating a stent comprising:

providing a stent;

providing a first coating composition comprising a first carrier and an HMG-CoA reductase inhibitor in an amount from about 1 to 50 wt. % of the first coating composition;

expanding the stent to an increased diameter;

applying the first coating composition to the stent;

drying the stent after the first coating composition is applied to the stent; and

applying a second coating composition comprising a polymeric biodegradable carrier to the dried stent.

7. The method of claim 6, wherein providing the first coating composition comprises mixing the HMG-CoA reductase inhibitor, the first carrier, and a solvent under conditions such that the HMG-CoA reductase inhibitor does not chemically react to any substantial degree with the first carrier.

8. The method of claim 6, wherein the first carrier comprises a nonpolymeric carrier.

9. The method of claim 8, wherein the first carrier is a liquid at body temperature.

10. The method of claim 8, wherein the first carrier is a solid at room temperature.

11. The method of claim 8, wherein the nonpolymeric carrier is selected from the group consisting of Vitamin E, Vitamin E acetate, Vitamin E succinate, oleic acid, peanut oil and cottonseed oil.

12. The method of claim 6, wherein the HMG-CoA reductase inhibitor is selected from the group consisting of cerivastatin, atorvastatin, simvastatin, fluvastatin, lovastatin, and pravastatin.

13. The method of claim 6, wherein applying the first coating composition comprises spraying or painting the first coating composition onto the stent, or immersing the stent in the first coating composition.

14. The method of claim 6, wherein providing the first coating composition comprises forming the first coating composition into a film, and applying the first coating comprises wrapping the film around the stent.

15. The method of claim 6, wherein the polymeric biodegradable carrier comprises a polymer selected from polycaprolactone, ethylene-vinyl acetate polymer, and a two-part silicone rubber.

16. The method of claim 6, wherein the second coating composition further comprises a substantially unreacted HMG-CoA reductase inhibitor.

17. The method of claim 6, wherein the stent further comprises one or more bioactive compounds selected from the group consisting of paclitaxel, paclitaxel analogs, actinomycin D, actinomycin D analogs, rapamycin, rapamycin analogs, and mixtures thereof.

18. The method of claim 6, wherein the HMG-CoA reductase inhibitor is released from the stent at a rate of >

20 μ

g/ml per day.