Polymers of fluorinated monomers and hydrocarbon monomers

• US 7,604,818 B2
• Filed: 12/22/2004
• Issued: 10/20/2009
• Est. Priority Date: 12/22/2004
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Advanced Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D.
• Primary Examiner(s): Mulcahy; Peter D.
• Assistant Examiner(s): HU, HENRY S
• Application Number:
  US11/021,775
• Publication Number:
  US 20060134165A1
• Time in Patent Office: 1,763 Days
• Field of Search: 604/265, 525/191, 524/500, 524/520, 524/544, 428/480, 424/423
• US Class Current: 424/423
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• 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 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08F 214/18 Monomers containing fluorine
• CPC Class Codes: C08F 295/00 Macromolecular compounds obtained by polymerisation using successively different catalyst types without deactivating the intermediate polymer
• CPC Class Codes: C08L 27/12 containing fluorine atoms
• CPC Class Codes: C09D 127/16 Homopolymers or copolymers of vinylidene fluoride

Abstract

A polymer of fluorinated monomers and hydrocarbon monomers is provided. It is also provided a polymer blend that contains a polymer formed of fluorinated monomers and hydrocarbon monomers and another biocompatible polymer. The polymer or polymer blend described herein and optionally a bioactive agent can form an implantable device such as a stent or a coating on an implantable device such as a drug-delivery stent, which can be used for treating or preventing a disorder such as atherosclerosis, thrombosis, restenosis, 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, or combinations thereof.

Claims

1. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises a random biocompatible polymer comprising fluorinated monomers and hydrocarbon monomers,

wherein the hydrocarbon monomers are CHR═

CH₂ in which R is selected from the group consisting of phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl, or CR₂═

CH₂ in which R is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl,

wherein the fluorinated monomers form about 25.01 mole % to about 99.99 mole % repeating units of the polymer, and

wherein the hydrocarbon monomers form about 74.99 mole % to about 0.01 mole % repeating units of the polymer.

2. The implantable device of claim 1, wherein the fluoro monomers are selected from the group consisting of —

CF₂—

CF₂—

, —

CH₂—

CF₂—

, —

CH₂—

CHF—

, —

CHF—

CHF—

, —

CClF—

CF₂—

, —

CF₂—

C(CF₃)F—

, —

CHF—

C(CF₃)F—

, —

CF₂—

C(CF₃)H—

, —

CF₂—

CRF—

, —

CHF—

CRF—

, —

CF₂—

CRH—

, —

CH₂—

CRF—

, and —

CFH—

CRH—

where R are hydrogen, Cl, Br, I, methyl, ethyl, n-propyl, iosopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic, heteroaryl, fluorinated short chain alkyl groups, fluorinated phenyl, fluorinated cyclic alkyl, fluorinated heterocyclic, and combinations thereof.

3. The implantable device of claim 1, wherein the hydrocarbon monomer is selected from the group consisting of one or more isobutylene, styrene, methyl styrene, and alkyl substituted styrene.

4. The implantable device of claim 1, wherein the biocompatible polymer has a structure of any of formulae II-III:

5. The implantable device of claim 1, which is a drug-delivery stent, wherein the coating further comprises a bioactive agent.

6. The drug-delivery stent of claim 5, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, prodrugs thereof, co-drugs thereof, and a combination thereof.

7. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises a random biocompatible polymer comprising fluorinated monomers and hydrocarbon monomers,

wherein the hydrocarbon monomers are CHR═

CH₂ in which R is selected from the group consisting of phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl or CR₂═

CH₂ in which R is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl,

wherein the fluorinated monomers form about 50.01 mole % to about 94.99 mole % units of the polymer, and

wherein the hydrocarbon monomers form about 49.99 mole % to about 5.01 mole % repeating units of the polymer.

8. A stent formed of a material comprising a random biocompatible polymer comprising fluorinated monomers and hydrocarbon monomers,

wherein the hydrocarbon monomers are CHR═

CH₂ in which R is selected from the group consisting of phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl or CR₂═

CH₂ in which R is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl,

wherein the fluorinated monomers form about 25.01 mole % to about 99.99 mole % repeating units of the polymer, and

wherein the hydrocarbon monomers form about 74.99 mole % to about 0.01 mole % repeating units of the polymer.

9. The stent of claim 8, wherein the fluoro monomers are selected from the group consisting of —

CF₂—

CF₂—

, —

CH₂—

CF₂—

, —

CH₂—

CHF—

, —

CHF—

CHF—

, —

CClF—

CF₂—

, —

CF₂—

C(CF₃)F—

, —

CHF—

C(CF₃)F—

, —

CF₂—

C(CF₃)H—

, —

CF₂—

CRF—

, —

CHF—

CRF—

, —

CF₂—

CRH—

, —

CH₂—

CRF—

, and —

CFH—

CRH—

where R are hydrogen, Cl, Br, I, methyl, ethyl, n-propyl, iosopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic, heteroaryl, fluorinated short chain alkyl groups, fluorinated phenyl, fluorinated cyclic alkyl, fluorinated heterocyclic, and combinations thereof.

10. A stent formed of a material comprising a random biocompatible polymer comprising fluorinated monomers and hydrocarbon monomers,

wherein the hydrocarbon monomers are CHR═

CH₂ in which R is selected from the group consisting of phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl CR₂═

CH₂ in which R is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic alkyl, and heteroaryl,

wherein the fluorinated monomers form about 50.01 mole % to about 94.99 mole % repeating units of the polymer,

wherein the hydrocarbon monomers form about 49.99 mole % to about 5.01 mole % repeating units of the polymer