Medical Devices Comprising Polymeric Drug Delivery Systems With Drug Solubility Gradients

• US 20140370071A1
• Filed: 08/29/2014
• Published: 12/18/2014
• Est. Priority Date: 07/20/2007
• Status: Active Grant

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Chen, Mingfei, Udipi, Kishore, Chen, Peiwen
• Granted Patent: US 9,056,156 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• 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 2300/60 characterised by a special physical form
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• 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 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 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: C08F 220/12 of monohydric alcohols or phenols
• CPC Class Codes: C08F 226/10 N-Vinyl-pyrrolidone

Abstract

Disclosed are drug delivery systems comprising drugs admixed with polymers having drug solubility gradients and methods of making the polymers. Also disclosed are medical devices having coatings thereon comprising the drug solubility gradient-containing polymers and at least one drug.

Claims

1. -15. (canceled)

16. A method of preparing a drug solubility gradient comprising:

preparing a first charge solution comprising at least one monomer under conditions that promote polymerization;

preparing at least one additional charge solution comprising at least one monomer;

adding said additional charge solution to said first charge solution; and

reacting said first charge solution and said additional charge solution until the desired degree of polymerization has been reached.

17. The method of claim 16 wherein said additional charge solution comprises from 2 to 10 charge solutions.

18. The method according to claim 16 wherein said adding step comprises a continuous addition of said additional charge solution to said first charge solution.

19. The method according to claim 16 wherein said adding step comprises a discontinuous addition of second said additional charge solution to said first solution.

20. The method according to claim 16 further comprising:

preparing a third solution comprising at least one monomer;

adding said third solution to the mixture of said first solution and second said additional charge solution; and

reacting said first solution and second said solution until the desired degree of polymerization has been reached.

21. The method according to either of claim 16 or 20 wherein said monomer is selected from the group comprising -caprolactone, polyethylene glycol (PEG), trimethylene carbonate, lactide, glycolide, p-dioxanone, methyl methacrylate, ethy methacrylate, propyl methacryalte, butyl methacrylate, pentyl methacrylate, hexyl methacrylate, heptyl methacrylate, octyl methacryalte, dodecylmethacryalte, 2-(ethoxy ethylmethacrylate), glycidyl methacrylate, poly(ethylene glycol) methacrylate, methyl acrylate, ethy acrylate, propyl acryalte, butyl acrylate, pentyl acrylate, hexyl acrylate, heptyl acrylate, octyl acryalte, dodecyl acryalte, 2-ethoxyethyl acrylate, glycidyl acrylate, poly(ethylene glycol) acrylate, N-vinyl pyrrolidinone, and derivatives thereof.

22. The method according to claim 16 wherein said drug solubility gradient further contains at least one drug.

23. The method according to claim 22 wherein said drug is selected from the group consisting of FKBP-12 binding agents, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARγ

), hypothemycin, nitric oxide, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids.

24. The method according to claim 23 wherein said drug comprises at least one compound selected from the group consisting of sirolimus (rapamycin), tacrolimus (FK506), everolimus (certican), temsirolimus (CCI-779) and zotarolimus (ABT-578).

25. The method according to claim 16 further comprising the step of coating said polymer comprising a drug solubility gradient on a vascular stent.

26. The method according to claim 16 further comprising the step of fabricating a vascular stent from said polymer comprising a drug solubility gradient.