Microparticle coated medical device

• US 20040052859A1
• Filed: 09/15/2003
• Published: 03/18/2004
• Est. Priority Date: 05/09/2001
• Status: Active Grant

• Current Assignee: Daryush Mirzaee, Deborra Sanders-Millare, Sameer Harish, Steven Z. Wu, Syed F.A. Hossainy
• Original Assignee: Daryush Mirzaee, Deborra Sanders-Millare, Sameer Harish, Steven Z. Wu, Syed F.A. Hossainy
• Inventors: Mirzaee, Daryush, Hossainy, Syed F. A., Wu, Steven Z., Sanders-Millare, Deborra, Harish, Sameer
• Granted Patent: US 8,603,536 B2
• Time in Patent Office: Days
• US Class Current: 424/490
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• 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 2300/606 Coatings
• CPC Class Codes: A61L 2300/622 Microcapsules
• 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: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids

Abstract

A drug-loaded microparticle is applied to a medical device for subsequent application to biological tissues. A method of formulating a drug-loaded microparticle and applying it to the surface of a medical device, such as a stent, is disclosed. The drug-loaded microparticle is formulated by combining a drug with various chemical solutions. Specified sizes of the microparticles and amounts of drug(s) contained within the microparticles may be varied by altering the proportions of the chemicals/solutions. In addition to various drugs, therapeutic substances and radioactive isotopes may also be loaded into the microparticles. The drug-loaded microparticle are suspended in a polymer solution forming a polymer matrix. The polymer matrix may be applied to the entire surface or only selected portions of the medical device via dipping, spraying or combinations thereof.

Claims

1. A drug-loaded microparticle formulation method comprising:

providing a first solution including an amount of a chemical dissolved in a volume of water;

adding a volume of a water soluble drug into said first solution, to form a second solution;

combining a volume of a curing agent solution with a volume of said second solution to form a final solution; and

adding a volume of said final solution into an oil bath forming one or more droplets suspended in said bath.

2. The method of claim 1, wherein said chemical comprises a chemical taken form the group consisting of polyethylene glycol diacrylate (PEGDA), vinyl pyrrolidove (VP), and poly alginate.

3. The method of claim 1, wherein said oil bath comprises a vortexed oil bath.

4. The method of claim 1, wherein said water soluble drug comprises a water soluble drug taken from the group consisting of dexamethasone and actinomycin-D (Ac/D).

5. The method of claim 1, wherein said curing agent solution comprises 10% w/w 2,2, dimethoxy 2 phenyl acetophenone solution dissolved in vinyl pyrrolidove.

6. A drug-loaded microparticle formulation method comprising:

providing a first solution including an amount of material dissolved in a volume of solvent;

adding a volume of a water soluble drug into said first solution to form a mixture;

combining a volume of a second solution with a volume of said mixture to form a final solution; and

evaporating a solvent from said final solution to form one or more microparticles.

7. The method of claim 6, further comprising collecting said microparticles from any remaining solution.

8. The method of claim 6, wherein said material comprises cellulose acetate phthalate (CAP).

9. The method of claim 6, wherein said evaporating of said solvent proceeds for 24 hours at 30°

C.

10. The method of claim 6, wherein said solvent comprises acetone.

11. A method of applying one or more microparticles to a medical device comprising:

providing a polymer solution;

combining one or more microparticles in said polymer solution to form a suspension;

applying said suspension to a surface of said medical device; and

centrifuging said medical device.

12. The method of claim 11, wherein said centrifuging of said medical device produces a coating having a relatively smooth surface texture.

13. The method of claim 11, further comprising, after said providing a polymer solution and centrifuging said medical device, respectively:

coating said medical device with a layer of said polymer solution;

spraying a co-solvent solution over said coating, said coating being completely covered by said co-solvent solution.

14. The method of claim 11, wherein said applying said suspension comprises selectively dipping said medical device in said suspension.

15. The method of claim 14, wherein said selectively dipping said medical device comprises dipping only a first end and a second end of said medical device.

16. The method of claim 11, wherein said polymer solution is ethylene vinyl alcohol (EVOH).

17. A drug loaded medical device comprising a first polymer matrix coated on a surface of said device, said first polymer matrix including one or more microparticles suspended in a polymer solution, each of said microparticles having one or more drugs loaded within said microparticle.

18. The drug loaded medical device of claim 17, wherein said microparticle comprises a microparticle taken form the group consisting of PEGDA, Ac/D loaded CAP, and VP microparticles.

19. The drug loaded medical device of claim 17, wherein said microparticle is 0.5 to 2.0 microns (0.1×

10<sup>−

4</sup> mm to 0.5×

10<sup>−

4</sup> mm) in length.

20. The drug loaded medical device of claim 17, wherein said polymer solution comprises EVOH.

21. The drug loaded medical device of claim 18 further comprising a layer of EVOH coated on a surface of said device between said surface of said device and said first polymer matrix.

22. The drug loaded medical device of claim 17, further comprising a top coat of a co-solvent solution.

23. The drug loaded medical device of claim 17, farther comprising a second polymer matrix including one or more microparticles suspended in a polymer solution, each of said microparticles having one or more drugs loaded within said microparticle, wherein said first polymer matrix is coated on a first portion of said medical device and said second polymer matrix is coated on a second portion of said medical device.

24. The drug-loaded medical device of claim 23, wherein said first polymer comprises a PEGDA microparticle suspended in EVOH and said second polymer comprises Ac/D loaded CAP microparticle suspended in EVOH.