Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device

• US 8,435,550 B2
• Filed: 08/13/2008
• Issued: 05/07/2013
• Est. Priority Date: 12/16/2002
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Cheng, Jin, Dugan, Stephen, Stewart, Gordon, Zhang, Gina, Consigny, Paul, Feezor, Christopher, Park, Gene, Roorda, Wouter, Hossainy, Syed F. A., Kirsten, Nancy
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US12/191,209
• Publication Number:
  US 20090286761A1
• Time in Patent Office: 1,728 Days
• Field of Search: None
• US Class Current: 424/423
• 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

A drug-delivery system is provided including at least 100 μg of everolimus and clobetasol, such that the ratio of everolimus to clobetasol is at least 10:1 (w/w) or the amount of everolimus by weight is at least 10 times more than clobetasol. The system can be a stent. Also provided a method of treating restenosis or vulnerable plaque of a blood vessel, the method includes locally administering to a patient a first drug selected from a group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethylrapamycin (everolimus), 40-O-(3-hydroxy)propylrapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethylrapamycin, 40-O-tetrazolylrapamycin and 40-epi-(N1-tetrazolyl)rapamycin, and locally administering to a patient a second drug consisting of clobetasol, wherein the minimum amount of the first drug that is locally administered is 100 μg, and wherein the ratio of the first drug to the second drug is, for example, 10:1 to 100:1 (w/w).

Claims

1. A drug-delivery system, comprising:

at least 100 μ

g of everolimus; and

clobetasol, such that the amount of everolimus by weight is at least 10 times more than clobetasol.

2. The drug-delivery system of claim 1, wherein the system is a stent.

3. The drug-delivery system of claim 1. where the system is a polymeric coated stent, such that the everolimus and clobetasol are in the polymeric coating.

4. The drug-delivery system of claim 3, wherein the coating includes 2 layers or regions such that the everolimus is in one layer or region and the clobetasol is in another layer or region.

5. The drug-delivery system of claim 1, wherein the drugs are released in sequence.

6. The drug-delivery system of claim 1, wherein the drugs are released simultaneously.

7. The drug-delivery system of claim 1, wherein the drug release profile includes at least a period of overlapping or simultaneous release profile of the everolimus and clobetasol.

8. The drug-delivery system of claim 1, wherein the ratio of the everolimus to the clobetasol is 10:

1 to 100;

1 (w/w).

9. A stent, comprising:

a radially expandable body; and

a combination of (a) a first drug selected from a group consisting of rapamycin, Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethylrapamycin, 40-O-(3-hydroxy)propylrapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethylrapamycin, 40-O-tetrazolylrapamycin and 40-epi-(N1-tetrazoly)prapamycin, and (b) a second drug consisting of clobetasol, carried by the stent,

wherein the minimum amount of the first drug carried by the stent is 100 μ

g, and wherein the ratio of the first drug to the second drug is 10;

1 to 100;

1 (w/w).

10. The stent of claim 9, wherein the stent includes a coating carrying the first and second drugs.

11. The stent of claim 10, wherein the coating includes at least two layers such that the first drug is in one layer and the second drug is on another layer.

12. The stent of claim 9, wherein the stent is a bioabsorbable stent.

13. The stent of claim 12, wherein at least one of the drugs is in the body of the bioabsorbable stent and at least one of the drugs is in a coating on the bioabsorbable stent.