Medical device with crystalline drug coating

• US 9,056,152 B2
• Filed: 09/23/2011
• Issued: 06/16/2015
• Est. Priority Date: 08/25/2011
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Kangas, Steve, Feng, James, Chen, Yen-Lane, Zeng, Maggie
• Primary Examiner(s): Yuan, Dah-Wei D
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US13/242,445
• Publication Number:
  US 20130053947A1
• Time in Patent Office: 1,362 Days
• Field of Search: 604/509, 424/423, 424/448, 429/195.1
• US Class Current: 1/1
• CPC Class Codes: A61F 2/00 Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents as cosmetic articles, see the relevant subclasses, e.g. wigs, hair pieces, A41G3/00, A41G5/00; artificial nails A45D31/00; dental prostheses A61C13/00; materials for prostheses A61L27/00; artificial hearts A61M60/00; artificial kidneys A61M1/14
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61L 2300/20 containing or releasing organic materials
• 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 2300/63 Crystals
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C09D 5/16 Antifouling paints; Underwater paints

Abstract

A medical device having a polymer-free outer surface layer comprising a crystalline drug selected from the group consisting of everolimus, tacrolimus, sirolimus, zotarolimus, biolimus, and rapamycin. The device may be produced by a method comprising the steps of providing a medical device; applying a solution of the drug to said portion of the outer surface to form a coating of amorphous drug; and vapor annealing the drug with a solvent vapor to form crystalline drug; wherein a seed layer of a crystalline form of said drug having a maximum particle size of about 10 μm or less is applied to at least said portion of the outer surface of the device before or after applying the drug solution, but before vapor annealing the amorphous coating.

Claims

1. A method of forming a coating comprising a drug on at least a portion of an outer surface of a medical device, the drug being a member of the group consisting of everolimus, tacrolimus, sirolimus, zotarolimus, biolimus, and rapamycin, the method comprising the steps of:

providing a medical device;

applying a solution of the drug to said portion of the outer surface to form a coating of amorphous drug;

providing crystals of the drug;

grinding the crystals of the drug to form microcrystals of the drug having a maximum size of about 10 μ

m or less;

applying the microcrystals of the drug to at least said portion of the outer surface of the device; and

vapor annealing the coating of amorphous drug with a solvent vapor to form crystalline drug;

the solvent selected from the group consisting of alcohols, acetonitrile, ethers, ketones solvents, halogenated solvents, aliphatic hydrocarbons, aromatic hydrocarbons, and ester solvents,

wherein the microcrystals of the drug are applied before or after applying the drug solution, but prior to any vapor annealing of the coating of amorphous coating.

2. A method as in claim 1 wherein the drug is everolimus.

3. A method as in claim 1 wherein the microcrystals of the drug form a seed layer on the portion of the outer surface of the device having a coat weight of less than 0.05 μ

g/mm².

4. A method as in claim 1 wherein the microcrystals are seed layer is applied from suspension in a liquid vehicle.

5. A method as in claim 1 wherein the solvent vapor is generated by vaporization of a liquid solvent composition in a chamber and the liquid solvent composition further comprises a non-volatile solute.

6. A method as in claim 1 wherein the medical device is a stent.

7. A method as in claim 6 wherein the device is a metal stent having grooves or depressions thereon, the drug solution is free of any excipient, and the drug solution is applied to said grooves or depressions on the outer surface of the stent.

13. The method of claim 6 wherein the medical device is a catheter balloon.

8. A method of forming a coating comprising a drug on at least a portion of an outer surface of a medical device, the drug being a member of the group consisting of everolimus, tacrolimus, sirolimus, zotarolimus, biolimus, and rapamycin, the method comprising the steps of:

applying a solution of the drug to said portion of the outer surface to form a coating of amorphous drug;

providing crystals of the drug;

preparing a microcrystalline form of said drug by breaking the crystals of the drug into microcrystals having a maximum particle size of about 10 μ

m or less;

applying the microcrystals to at least said portion of the outer surface of the device; and

subsequently vapor annealing the amorphous coating with a solvent vapor to form crystalline drug;

the solvent vapor consisting of a vapor of a solvent selected from the group consisting of alcohols, acetonitrile (ACN);

ethers, ketones solvents, halogenated solvents, aliphatic hydrocarbons, aromatic hydrocarbons, and ester solvents,

wherein the microcrystals are applied to at least said portion of the outer surface of the device before or after applying the drug-solution, but prior to any vapor annealing of the amorphous coating.

9. A method as in claim 8 wherein the medical device is a catheter balloon.

10. A method as in claim 9 wherein the drug is everolimus.

11. A method as in claim 8 wherein the medical device is a stent.

12. A method as in claim 11 wherein the drug is everolimus.

14. The method of claim 8 wherein the step of preparing a microcrystalline form of said drug comprises the step of grinding the crystallized drug to a desired size range.

15. The method of claim 8 wherein during the step of preparing a microcrystalline form of said drug, the drug crystals are subjected to sonication in a slurry.

16. A method of forming a coating comprising a drug on at least a portion of an outer surface of a medical device, the drug being a member of the group consisting of everolimus, tacrolimus, sirolimus, zotarolimus, biolimus, and rapamycin, the method comprising the steps of:

providing a medical device;

applying a solution of the drug to said portion of the outer surface to form a coating of amorphous drug;

providing seed crystals of the drug, the seed crystals having a major dimension ranging from about 10 nm to about 20 μ

m;

disposing the seed crystals of the drug on at least said portion of the outer surface of the device;

vapor annealing the drug with a solvent vapor to form crystalline drug;

the solvent selected from the group consisting of alcohols, acetonitrile, ethers, ketones solvents, halogenated solvents, aliphatic hydrocarbons, aromatic hydrocarbons, and ester solvents,

wherein the seed crystals of the drug are applied to at least said portion of the outer surface of the device before or after applying the drug solution, but prior to subjecting the medical device to any vapor annealing.