Biocompatible controlled release coatings for medical devices and related methods

• US 20060275340A1
• Filed: 08/12/2004
• Published: 12/07/2006
• Est. Priority Date: 08/13/2003
• Status: Active Grant

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Lyu, Su Ping, Udipi, Kishore, Cheng, Peiwen, Shalaby, Shalaby W., Campbell, Todd
• Granted Patent: US 9,687,368 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• 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 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/06 obtained otherwise than 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: C08L 65/04 Polyxylenes

Abstract

Biocompatible coatings for medical devices are disclosed. Specifically, polymer coatings designed to control the release of bioactive agents from medical devices in vivo are disclosed wherein the solubility parameters of polymers and drugs are closely matched to control elute rate profiles. The present application also discloses providing vascular stents with controlled release coatings and related methods for making these coatings.

Claims

1. An implantable medical device having a controlled release coating comprising:

a terpolymer-bipolymer blend having a total solubility parameter (δ

_T) approximately equal to a bioactive agent'"'"'s solubility parameter (δ

) and wherein δ

_T and δ

is between 15 J^1/2/cm^3/2 to 25 J^1/2/cm^3/2.

2. The controlled release coating according to claim 1 wherein said coating has a glass transition point (Tg) between approximately −

20°

C. and 50°

C.

3. The controlled release coating according to claim 1 wherein said terpolymer comprises relative weight percent concentrations of monomer subunits consisting essentially of vinyl acetate (VAc), alkyl methacrylate (AMA) and n-vinyl pyrrolidone (NVP) and said bipolymer comprises relative weight percent concentrations of monomer subunits consisting essentially of VAc and AMA.

4. The controlled release coating according to claim 3 wherein said relative weight percent concentrations of said monomer subunits in said terpolymer comprises from 7-30% (VAc), 40-75% (AMA) and 19-30% (NVP).

5. The controlled release coating according to claim 3 wherein said relative weight percent concentrations of said monomer subunits in said bipolymer comprises from 5-70% VAc and from 30-95% AMA.

6. The controlled release coating according to claim 3 wherein said alkyl methacrylate is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, and hexyl.

7. The controlled release coating according to any one of claims 1 though 6 wherein said δ

_T is approximately 15 to 21 and said polymer blend comprises from 25% to 80% bipolymer and from 20% to 75% terpolymer.

8. The controlled release coating according to any one of claims 1-6 wherein said bipolymer has a lower Tg than said terpolymer.

9. The controlled release coating according to claim 1 wherein said bioactive agent is selected from the group consisting of anti-proliferatives including, but not limited to, macrolide antibiotics including FKBP 12 binding compounds, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, peroxisome proliferator-activated receptor gamma ligands (PPARγ

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

10. The controlled release coating according to claim 9 wherein said antiproliferative is a FKBP 12 binding compound.

11. The controlled release coating according to claim 10 wherein said FKBP 12 binding compound is a macrolide antibiotic.

12. The controlled release coating according to claim 11 wherein said macrolide antibiotic is rapamycin, evrolimus or ABT-578.

13. A vascular stent comprising a structure:

said structure comprising a material having a hydrophobic polymer disposed thereon; and

a controlled release coating over said hydrophobic polymer wherein said controlled release coating comprises a bioactive agent-containing terpolymer-bipolymer blend wherein the difference between the solubility parameters of said terpolymer-bipolymer blend and said bioactive agent is no greater than 10 J^1/2/cm^3/2 and the total solubility parameter (δ

_T) of said bioactive agent-containing terpolymer-bipolymer blend is no greater than 25 J^1/2/cm^3/2.

14. The vascular stent according to claim 13 wherein said hydrophobic polymer is parylene or a parylene derivative.

15. The vascular stent according to claim 13 wherein said terpolymer comprises relative weight percent concentrations of monomer subunits consisting essentially of vinyl acetate (VAc), alkyl methacrylate (AMA) and n-vinyl pyrrolidone (NVP) and said bipolymer comprises relative weight percent concentrations of monomer subunits consisting essentially of VAc and AMA.

16. The vascular stent according to claim 15 wherein said relative weight percent concentrations of said monomer subunits in said terpolymer comprises from 7-30% (VAc), 40-75% (AMA) and 19-30% (NVP).

17. The vascular stent according to claim 13 wherein said relative weight percent concentrations of said monomer subunits in said bipolymer comprises from 5-70% VAc and from 30-95% AMA.

18. The vascular stent according to claim 15 wherein said alkyl methacrylate is selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, and hexyl.

19. The vascular stent according to any one of claims 13 though 18 wherein said δ

T is approximately 15 to 21′ and

said polymer blend comprises from 25% to 80% bipolymer and from 20% to 75% terpolymer.

20. The vascular stent according to any one of claims 13-18 wherein said bipolymer has a lower Tg than said terpolymer.

21. The vascular stent according to claim 13 wherein said bioactive agent is selected from the group consisting of anti-proliferatives including, but not limited to, macrolide antibiotics including FKBP 12 binding compounds, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, peroxisome proliferator-activated receptor gamma ligands (PPARγ

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

22. The vascular stent according to claim 21 wherein said antiproliferative is a FKBP 12 binding compound.

23. The vascular stent according to claim 22 wherein said FKBP 12 binding compound is a macrolide antibiotic.

24. The vascular stent according to claim 23 wherein said macrolide antibiotic is rapamycin, evrolimus or ABT-578.