Drug-delivery stent formulations for restenosis and vulnerable plaque

• US 8,017,140 B2
• Filed: 05/21/2007
• Issued: 09/13/2011
• Est. Priority Date: 06/29/2004
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Zhang, Gina, Kilpatrick, Deborah, Stewart, Gordon, Ellis, Jeffrey, Park, Gene, Tang, Yiwen, Consigny, Paul, Hossainy, Syed Faiyaz Ahmed
• Primary Examiner(s): FUBARA, BLESSING M
• Application Number:
  US11/804,997
• Publication Number:
  US 20070269484A1
• Time in Patent Office: 1,576 Days
• Field of Search: 424/486, 424/422, 424/426, 424/423
• US Class Current: 424/422
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• 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 2300/422 Anti-atherosclerotic agents
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• 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: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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

Abstract

Drug-delivery stents capable of providing release of two or more drugs such as everolimus and estradiol are provided. The stents can be used for treating a disease such as restenosis and vulnerable plaque.

Claims

1. A drug delivery stent, comprising:

a primer;

a reservoir layer comprising estradiol;

an intercoat;

a second reservoir layer comprising everolimus encapsulated in nano- and/or micro- particles and unencapsulated everolimus.

2. The drug delivery stent of claim 1, wherein the estradiol is 17-beta-estradiol.

3. The drug delivery stent of claim 1, wherein the stent is capable of:

burst and/or pulsed and sustained release of everolimus; and

sustained release of estradiol.

4. The drug delivery stent of claim 1, wherein the first drug reservoir layer and/or the second drug reservoir layer further comprise a polymer wherein the polymer may be the same or different in each layer.

5. The drug delivery stent of claim 4, wherein the first and second polymers are independently selected from the group consisting of poly(ethylene vinyl alcohol) (EVAL), poly(D,L-lactic acid) (PDLLA), poly(ester amide) (PEA), polybutylmethacrylate (PBMA), poly(ether ester), and poly(vinylidene fluoride) (PVDF).

6. A method of treating a disorder in a patient comprising implanting in the patient the stent of claim 1, wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor, and combinations thereof.

7. The method of claim 6, wherein:

the everolimus is released from an 18 mm stent at a rate of about 15 μ

g to about 40 μ

g per day for at least one day after implantation.

8. The method of claim 7, wherein the everolimus is released from the stent at a rate of about 15 μ

g to about 40 μ

g per day for one to three days after implantation.

9. The method of claim 6, wherein:

the everolimus is released from a 13 mm stent at a rate of about 10 μ

g to about 27 μ

g per day for at least one day after implantation.

10. The method of claim 6, wherein:

the everolimus is released from an 8 mm stent at a rate of about 6 μ

g to about 17.2 μ

g per day for at least one day after implantation.