Methods of treatment with drug eluting stents with prolonged local elution profiles with high local concentrations and low systemic concentrations

• US 9,358,096 B2
• Filed: 06/03/2013
• Issued: 06/07/2016
• Est. Priority Date: 05/01/2007
• Status: Active Grant

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Stalker, Kent C. B., McIntosh, Winnette S., Jayasinghe, Dudley S., Orr, Gregory C., Papp, John E., Schwartz, Lewis B.
• Primary Examiner(s): Sweet, Thomas J
• Assistant Examiner(s): Mathew, Seema
• Application Number:
  US13/908,854
• Publication Number:
  US 20130268061A1
• Time in Patent Office: 1,100 Days
• Field of Search: 623/1.42, 623/1.46
• US Class Current: 1/1
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2002/91583 by a bridge, whereby at least one of its ends is connected along the length of a strut between two consecutive apices within a band
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/022 Metals or alloys
• 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

Abstract

A drug eluting stent can include a stent body having a polymeric coating with a lipophilic and/or hydrophilic element. A drug that has a bioactivity that inhibits cell proliferation can be disposed in the polymeric coating. The drug can be present in the polymer at an amount greater than or equal to about 150 μg/cm². The polymeric coating and drug are configured to cooperate so as to form a diffusion pathway with tissue when the stent is disposed in a body lumen such that the drug preferentially diffuses into the tissue over a body fluid passing through the body lumen such that a maximum systemic blood concentration of the drug is less than about 40 ng/ml.

Claims

1. A method of treating peripheral vascular disease in a subject, the method comprising:

implanting in a peripheral artery of a subject a drug eluting stent comprising;

a self-expanding stent body of 130 mm to 170 mm in length, the self-expanding stent body being a design of annular elements and interconnectors where the annular elements are connected adjacently by at least one interconnector;

a polymeric coating disposed on the stent body, the polymeric coating being 2 μ

m to 50 μ

m in thickness;

a lipophilic drug disposed in the polymeric coating, the lipophilic drug being present at an amount between about 4 mg to about 8 mg;

wherein the maximum systemic blood concentration of the lipophilic drug in the subject is about 30 ng/ml or less than 30 ng/ml.

2. The method as in claim 1, wherein the lipophilic drug is present in an amount greater than or equal to 200 μ

g/cm².

3. The method as in claim 1, wherein the lipophilic drug is everolimus, zotarolimus, tacrolimus, paclitaxel, or a combination thereof.

4. The method as in claim 3, wherein the lipophilic drug is present at an amount between about 5 mg and about 7 mg.

5. The method as in claim 1, wherein the lipophilic drug is present at an amount between about 5 mg and about 7 mg.

6. The method as in claim 1, wherein the polymeric coating ranges from about 4 μ

m to about 25 μ

m in thickness.

7. The method as in claim 1, wherein the polymeric coating comprises a primer layer disposed on the stent body, a drug-loaded layer disposed on the primer layer, and a topcoat layer disposed on the drug-loaded layer.

8. The method as in claim 7, wherein the polymeric coating is characterized by at least one of the following:

the primer layer being from about 1% to about 20% of the total coating thickness;

the drug-loaded layer being from about 25% to about 90% of the total coating thickness;

or

the topcoat being from about 5% to about 50% of the total coating thickness.

9. The method as in claim 8, wherein the stent body is nitinol, the lipophilic drug is everolimus, and the polymer of the polymeric coating is an ethylenevinylalcohol copolymer.

10. The method as in claim 1, wherein the lipophilic drug is everolimus.

11. The method as in claim 1, wherein the maximum systemic blood concentration of the lipophilic drug in the subject is about 20 ng/ml or less than 20 ng/ml.

12. The method as in claim 1, wherein the maximum systemic blood concentration of the lipophilic drug in the subject is about 10 ng/ml or less than 10 ng/ml.

13. The method as in claim 1, wherein the stent body is formed from Nitinol.

14. The method as in claim 1, wherein the stent is implanted in a superficial femoral artery.

15. The method as in claim 1, wherein the stent is implanted in an iliofemoral artery.

16. A method of treating peripheral vascular disease in a subject, the method comprising:

implanting in a peripheral artery of a subject a drug eluting stent comprising;

a self-expanding stent body of Nitinol, the self-expanding stent body being a design of annular elements and interconnectors where the annular elements are connected adjacently by at least one interconnector;

a polymeric coating disposed on the stent body, the polymeric coating being 5 μ

m to 20 μ

m in thickness; and

everolimus disposed in the polymeric coating;

wherein the maximum systemic blood concentration of everolimus in the subject is about 30 ng/ml or less than 30 ng/ml;

and

wherein

the stent is 28 mm in length and 10 mm in diameter, and the amount of everolimus is about 1.07 mg;

or

the stent is 100 mm in length and 7 mm in diameter, and the amount of everolimus is about 3.5 mg.

17. The method as in claim 16, wherein the stent is 100 mm in length and 7 mm in diameter.

18. The method as in claim 16, wherein the stent is 28 mm in length and 10 mm in diameter.

19. The method as in claim 18, wherein the peripheral artery of the subject is a superficial femoral artery.

20. The method as in claim 18, wherein the peripheral artery of the subject is an iliofemoral artery.

21. The method as in claim 17, wherein the peripheral artery of the subject is a superficial femoral artery.

22. The method as in claim 17, wherein the peripheral artery of the subject is an iliofemoral artery.