Coatings Including Dexamethasone Derivatives And Analogs And Olimus Drugs

• US 20100082095A1
• Filed: 09/29/2008
• Published: 04/01/2010
• Est. Priority Date: 09/29/2008
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D., Toner, John L., Cromack, Keith R.
• Granted Patent: US 8,092,822 B2
• Time in Patent Office: Days
• US Class Current: 623/1.420
• 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 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 9/08 Vasodilators for multiple indications
• 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: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C08L 27/16 Homopolymers or copolymers or vinylidene fluoride

Abstract

The present invention encompasses a coating on the surface of a substrate and the coated substrates. The coating includes a polymer, an olimus drug (sirolimus, everolimus, zotarolimus, etc.), and a dexamethasone derivative. The polymer may be a hydrophobic polymer, preferably a fluoropolymer, and more preferably a fluoropolymer with at least 25% vinylidene fluoride by weight.

Claims

1. A medical device comprising:

a device body with an outer surface;

a coating comprising

one or more coating layers disposed over the surface;

a hydrophobic polymer;

an olimus drug; and

a dexamethasone derivative or analog;

wherein the dexamethasone derivative or analog in the coating is substantially amorphous.

2. The device of claim 1, wherein the olimus drug dose is between about 10 and about 600 μ

g/cm² and the dose of dexamethasone derivative or analog is between 10 and about 600 μ

g/cm.²

3. The device of claim 1, wherein one coating layer comprises the olimus drug and the dexamethasone derivative or analog.

4. The device of claim 1, wherein the mass ratio of olimus drug to dexamethasone derivative or analog is between about 1:

1 and about 1;

4.

5. The device of claim 1, wherein the device is an implantable medical device.

6. The device of claim 5, wherein the implantable medical device is a stent.

7. The device of claim 1, wherein the device is a catheter balloon.

8. The device of claim 1, wherein the hydrophobic polymer is a fluoropolymer.

11. The device of claim 1, wherein the olimus drug is selected from the group consisting of sirolimus, everolimus, zotarolimus, biolimus A9, novolimus, temsirolimus, and AP23572.

12. The device of claim 1, wherein the dexamethasone derivative or analog is a compound of the formula, or any combination of compounds represented by the formula:

wherein R1 may be selected from the group the consisting of

wherein R₂ is selected from the group consisting of (C1-C16)alkyl, (C2-C16)alkenyl, (C2-C16)alkynyl, (C3-C10)cycloalkyl, phenyl, ester, carbonate, ether, and ketone;

wherein

any one or more hydrogen atoms on the cycloalkyl or phenyl ring is optionally substituted with a substituent selected from the group consisting of alkyl, alkenyl, and alkynyl;

any one or more hydrogen atoms on R₂ are optionally replaced with chlorine, fluorine or a combination thereof; and

the total number of carbon atoms in R₂ is not more than 16.

13. The device of claim 1, wherein the dexamethasone derivative or analog is a compound of the formula, or any combination of compounds represented by the formula:

wherein R1 may be selected from the group the consisting of

wherein R₂ is selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, tert-butyl, n-pentyl, n-hexyl, phenyl, benzyl, pentadecane (C₁₅H₃₁), tetrahydrophthalate, 4-pyridinium, diethylaminomethylene, and metasulfobenzoate.

14. The device of claim 1, wherein the dexamethasone derivative or analog is selected from the group consisting of dexamethasone acetate, dexamethasone palmitate, dexamethasone diethylaminoacetate, dexamethasone isonicotinate, dexamethasone tert-butylacetate, dexamethasone tetrahydrophthalate, and combinations thereof.

15. The device of claim 14, wherein the dexamethasone derivative or analog is dexamethasone acetate.

16. The device of claim 15, wherein the hydrophobic polymer is PVDF-HFP, and the olimus drug is selected from the group consisting of sirolimus, everolimus, zotarolimus, biolimus A9, novolimus, temsirolimus, AP23572, and combinations thereof.

17. The device of claim 1, wherein the cumulative drug release of the olimus drug is not more than 50% of the total olimus drug content at 24 hours.

18. The device of claim 1, wherein the cumulative drug release of the dexamethasone derivative or analog is not more than 50% of the total dexamethasone derivative or analog drug content at 24 hours.

19. A method of treating a medical condition in a patient comprising, implanting in the patient in need thereof a device according to claim 1.

20. The method of claim 19, wherein the medical condition is selected from the group consisting of restenosis, atherosclerosis, thrombosis, 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 obstruction, and combinations of these.

21. The method of claim 19, wherein the medical device is an implantable medical device.

22. The method of claim 21, wherein the implantable medical device is a stent.

23. The method of claim 22, wherein the olimus drug is zotarolimus and the dexamethasone derivative or analog is dexamethasone acetate.

24. The method of claim 23, wherein the cumulative drug release of the zotarolimus is not more than 50% of the total zotarolimus content at 24 hours.

25. The method of claim 22, wherein the cumulative drug release of the dexamethasone acetate is not more than 50% of the total dexamethasone acetate content at 24 hours.

26. The method of claim 23, wherein the cumulative drug release of the dexamethasone acetate is not more than 50% of the total dexamethasone acetate content at 24 hours.

9. The device of claim 9, wherein the hydrophobic polymer is fluoropolymer comprising at least 25% vinylidene fluoride by weight.

10. The device of claim 10, wherein the hydrophobic polymer is PVDF-HFP.