Polymers of fluorinated monomers and hydrocarbon monomers

• US 20060134165A1
• Filed: 12/22/2004
• Published: 06/22/2006
• Est. Priority Date: 12/22/2004
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen D.
• Granted Patent: US 7,604,818 B2
• Time in Patent Office: Days
• US Class Current: 424/422
• 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. A biocompatible polymer comprising fluorinated monomers and hydrocarbon monomers,

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.

3. The biocompatible polymer of claim 1, having the structure of formula

4. The biocompatible polymer of claim 3,

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, or combinations thereof, and

wherein the hydrocarbon monomers can be CHR═

CH₂ or CR₂═

CH₂ in which R can be hydrogen, methyl, ethyl, n-propyl, isopropyl, short chain alkyl groups, phenyl, substituted phenyl, cyclic alkyl, heterocyclic, heteroaryl, or combinations thereof.

5. The biocompatible polymer of claim 3 wherein the hydrocarbon monomer is one or more isobutylene, styrene, methyl styrene, alkyl substituted styrene, ethylene, propylene, and butylenes.

6. The biocompatible polymer of claim 3 having a structure of any of formulae II-III:

7. A biocompatible polymer blend comprising the biocompatible polymer of claim 1 and at least one other biocompatible polymer.

8. A biocompatible polymer blend comprising the biocompatible polymer of claim 3 and at least one other biocompatible polymer.

9. A biocompatible polymer blend comprising the biocompatible polymer of claim 4 and at least one other biocompatible polymer.

10. The polymer blend of claim 9, wherein the other biocompatible polymer is selected from the group consisting of poly(ester amide), polyesters, polyhydroxyalkanoates (PHA), poly(3-hydroxyalkanoates), poly(3-hydroxypropanoate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), poly(3-hydroxyhexanoate), poly(3-hydroxyheptanoate), poly(3-hydroxyoctanoate), poly(4-hydroxyalknaotes), poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), poly(4-hydroxyhexanote), poly(4-hydroxyheptanoate), poly(4-hydroxyoctanoate) copolymers including 3-hydroxyalkanoate, 4-hydroxyalkanoate monomers described herein or blends thereof, poly(D,L-lactide), poly(L-lactide), polyglycolide, poly(D,L-lactide-co-glycolide), poly(L-lactide-co-glycolide), polycaprolactone, poly(lactide-co-caprolactone), poly(glycolide-co-caprolactone), poly(dioxanone), poly(ortho esters), poly(anhydrides), poly(tyrosine carbonates) and derivatives thereof, poly(tyrosine ester) and derivatives thereof, poly(imino carbonates), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), polycyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyurethanes, polyphosphazenes, silicones, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, methacrylic polymers and copolymers, acrylic polymers and copolymers, poly(methylmethacrylate), poly(ethyl methacrylate), poly(isopropyl methacrylate), poly(n-propyl methacrylate), poly(n-butyl methacrylate), vinyl halide polymers and copolymers polyvinyl chloride, poly(vinylidene fluoride), poly(vinylidene fluoride-co-hexafluoropropylene), polyvinyl ethers polyvinyl methyl ether, polyvinylidene halides, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, polystyrene, polyvinyl esters, polyvinyl acetate, copolymers of vinyl monomers, ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers, polyamides, Nylon 66 and polycaprolactam, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, poly(glyceryl sebacate), poly(propylene fumarate), epoxy resins, polyurethanes, rayon, rayon-triacetate, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polyethers, poly(ethylene glycol) (PEG), copoly(ether esters), copoly(ethylene oxide-co-lactic acid) (PEO/PLA), polyalkylene oxides, poly(ethylene oxide), poly(propylene oxide), polyalkylene oxalates, phosphoryl choline, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers, polymers and copolymers of hydroxyethyl methacrylate (HEMA), polymers and copolymers of hydroxypropyl methacrylate (HPMA), polymers and copolymers of hydroxypropylmethacrylamide, polymers and copolymers of PEG acrylate (PEGA), polymers and copolymers of PEG methacrylate, polymers and copolymers of 2-methacryloyloxyethylphosphorylcholine (MPC), polymers and copolymers of n-vinyl pyrrolidone (VP), polymers and copolymers of carboxylic acid bearing monomers, polymers and copolymers of methacrylic acid (MA), polymers and copolymers of acrylic acid (AA), polymers and copolymers of alkoxymethacrylate, polymers and copolymers of alkoxyacrylate, polymers and copolymers of 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-isoprene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene-PEG, polycaprolactone-PEG (PCL-PEG), PLA-PEG, poly(methyl methacrylate)-PEG (PMMA-PEG), polydimethylsiloxane-co-PEG (PDMS-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), PLURONIC™

surfactants (polypropylene oxide-co-polyethylene glycol), poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), biomolecules, collagen, chitosan, alginate, fibrin, fibrinogen, cellulose, starch, collagen, dextran, dextrin, fragments and derivatives of hyaluronic acid, heparin, fragments and derivatives of heparin, glycosamino glycan (GAG), GAG derivatives, polysaccharide, elastin, chitosan, alginate, and combinations thereof.

11. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the biocompatible polymer of claim 1.

13. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the biocompatible polymer of claim 3.

14. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the biocompatible polymer of claim 4.

15. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the biocompatible polymer of claim 5.

16. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the biocompatible polymer of claim 6.

17. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the polymer blend of claim 7.

18. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the polymer blend of claim 10.

19. The implantable device of claim 13, which is a drug-delivery stent, wherein the coating further comprises a bioactive agent.

20. The drug-delivery stent of claim 19, 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.

21. A stent formed of a material comprising the composition of claim 1.

22. A stent formed of a material comprising the composition of claim 3.

23. A stent formed of a material comprising the composition of claim 10.

24. The stent of claim 23, further comprises a bioactive agent.

25. A method of treating a disorder in a patient comprising implanting in the patient the implantable device of claim 13, wherein the disorder is selected from the group consisting of 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, and combinations thereof.

26. A method of treating a disorder in a patient comprising implanting in the patient the implantable device of claim 20, wherein the disorder is selected from the group consisting of 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, and combinations thereof.

2. A biocompatible polymer comprising fluorinated monomers and hydrocarbon monomers,

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.

12. An implantable device having a biocompatible coating thereon, wherein the biocompatible coating comprises the biocompatible polymer of claim 2.