Poly(ester amide) filler blends for modulation of coating properties

• US 7,390,497 B2
• Filed: 10/29/2004
• Issued: 06/24/2008
• Est. Priority Date: 10/29/2004
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Tang, Yiwen, Kleiner, Lothar, Pacetti, Stephen Dirk, Zhang, Gina, DesNoyer, Jessica Renee, Hossainy, Syed Faiyaz Shmed
• Primary Examiner(s): WOODWARD, ANA LUCRECIA
• Application Number:
  US10/976,551
• Publication Number:
  US 20060093842A1
• Time in Patent Office: 1,334 Days
• Field of Search: 528/272, 128897-899, 623/1.15, 623/1.38, 623/1.42, 623/1.46, 623/900, 427/2.1, 427/487, 424/422, 424/423, 525/178, 525/419, 525/54.2, 525/54.21, 525/54.3, 525/54.42, 525/58, 525/60, 525/165, 525/166, 525/169, 525/170, 525/410, 525/415, 525/420, 525/423, 525/424, 525/425, 525/426, 525/430, 428/212, 428/480, 514/1, 514/2
• US Class Current: 424/422
• 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: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C08L 77/12 Polyester-amides
• CPC Class Codes: C09D 177/12 Polyester-amides
• CPC Class Codes: Y10S 623/90 Stent for heart valve
• CPC Class Codes: Y10T 428/31725 Of polyamide
• CPC Class Codes: Y10T 428/31786 Of polyester [e.g., alkyd, etc.]

Abstract

Provided herein is a PEA polymer blend and coatings or implantable devices formed therefrom. The PEA polymer blend is formed of a PEA polymer and a material capable of hydrogen bonding with the PEA. The PEA polymer blend can form a coating on an implantable device, one example of which is a stent. The coating can optionally include a biobeneficial material and/or optionally with a bioactive agent. The implantable device can be used to treat or prevent a disorder such as one 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.

Claims

1. A coating for an implantable device, comprising:

a poly(ester amide) (PEA) polymer comprising a polymer chain having amide groups in the chain, and

a material for hydrogen-bonding with the PEA,

wherein the polymer chain of one molecule of the PEA polymer hydrogen-bonds to a molecule of the material for hydrogen-bonding, which in turn hydrogen-bonds to the polymer chain of another molecule of the PEA polymer.

2. The coating of claim 1, wherein the PEA polymer comprises diacid, diol, and amino acid subunits in its backbone.

3. The coating of claim 1, wherein the PEA polymer is co-poly-{[N,N′

-sebacoyl-bis-(L-leucine)-1,6-hexylene diester]-[N,N′

-sebacoyl-L-lysine benzyl ester]} (PEA-Bz) or co-poly{[N,N′

-sebacoyl-bis-(L-leucine)-1,6-hexylene diester]-[N,N′

-sebacoyl-L-lysine 4-amino-TEMPO amide]} (PEA-TEMPO).

4. The coating of claim 3, further comprising a biobeneficial material selected from garlic oil, fullerene, heparin, hirudin, fibrin, hyaluronic acid, hydrophobically modified hyaluronic acid, chondroitan sulfate, glycosaminoglycans, chitin, poly(styrene sulfonate), or combinations thereof selected from poly(ethylene glycol) (PEG), garlic oil, fullerene, poly(propylene glycol), poly(tetramethylene glycol), heparin, hirudin, fibrin, elastin, hyaluronic acid, hydrophobically modified hyaluronic acid, chondroitan sulfate, glycosaminoglycans, chitin, chitosan, poly(styrene sulfonate), poly(2-hydroxylethyl methacrylate), poly(acrylamide), and poly(hydroxypropyl methacrylamide).

5. The coating of claim 1, wherein the material for hydrogen-bonding with PEA is selected from the group consisting of non-degradable polymers, biodegradable polymers and combinations thereof,

wherein the non-degradable polymer has a molecular weight below about 40,000 Daltons, and

wherein the biodegradable polymer can degrade into fragments having a molecular weight below about 40,000 Daltons.

6. The coating of claim 1, wherein the material for hydrogen-bonding with PEA is selected from the group consisting of polymers or copolymers of monomers containing a hydroxyl group, a carboxyl group, an ether group, a carbonyl group, a urethane group, a urea group, or an amino group, poly(vinyl alcohol), poly(vinyl alcohol-co-vinyl acetate), polyacrylic acid, polymethacrylic acid, poly(acrylamide), poly(hydroxypropyl methacrylamide), poly(2-hydroxyethyl methacrylate), poly(2-methoxyethyl methacrylate), poly(2-ethoxyethyl methacrylate), poly(2-methoxyethyl acrylate), poly(vinyl pyrrolidone), poly(pyrrole), poly(ethylene-co-vinyl alcohol), non-water soluble cellulose acetate, non-water soluble hydroxyethyl cellulose, non-water soluble hydroxypropyl cellulose, cellulose ethers, methyl cellulose and ethyl cellulose, poly(urethanes), poly(urethane-ureas), poly(ureas), poly(tetramethylene glycol), poly(propylene glycol), poly(ethylene glycol), poly(imino carbonates), peptides, gelatin, collagen, non-water soluble chitosan, agarose, elastin, poly(alginic acid), alginate, dextrose, dextran, poly(glutamic acid), poly(lysine), copolymers containing poly(ethylene glycol) and polybutylene terephthalate segments, poly(aspartic acid), poly(leucine), poly(leucine-co-hydroxyethyl glutamine), poly(benzyl glutamate), poly(glutamic acid-co-ethyl glutamate), poly(amino acids), poly(ortho esters), poly(anhydrides), poly(D,L-lactic acid), poly (L-lactic acid), poly(glycolic acid), copolymers of poly(lactic) and glycolic acid, poly(phospho esters), poly(-hydroxybutyrate), poly(caprolactone), poly(trimethylene carbonate), poly(oxaesters), poly(oxaamides), poly(ethylene carbonate), poly(propylene carbonate), poly(phosphoesters), poly(phosphazenes), copolymers thereof with poly(ethylene glycol), and combinations thereof.

7. The coating of claim 1, wherein the material for hydrogen-bonding with PEA is a-copolymer containing poly(ethylene glycol) and polybutylene terephthalate segments.

8. The coating of claim 7, wherein the PEA and the copolymer containing poly(ethylene glycol) and polybutylene terephthalate segments form a blend.

9. The coating of claim 7, wherein the PEA forms a PEA layer of coating, and wherein the copolymer containing poly(ethylene glycol) and polybutylene terephthalate segments forms a layer of coating separate from the PEA layer of coating.

10. The coating of claim 7, further comprising a biobeneficial material.

11. The coating of claim 1, further comprising a biobeneficial material selected from garlic oil, fullerene, heparin, hirudin, fibrin, hyaluronic acid, hydrophobically modified hyaluronic acid, chondroitan sulfate, glycosaminoglycans, chitin, poly(styrene sulfonate), or combinations thereof.

12. The coating of claim 1, wherein the material for hydrogen bonding with PEA is selected from the group consisting of dendrimers, star-shaped molecules, absorbable glass, and combinations thereof,

wherein the dendrimer or star-shaped molecule has a group selected from the group consisting of —

NH₂, —

COOH, —

OH groups and combinations thereof, and

wherein the absorbable glass comprises Fe, Ca, or phosphate, or combinations thereof.

13. The coating of claim 1, wherein the material for hydrogen bonding with PEA is a bioactive component selected from the group consisting of laminin V, silk elastin, hyaluronic acid-benzyl ester, resten NG, antisense oligonucleotide fragment with antiproliferative properties, MMPI, cellulose acetate-co-pentasaccharide, and combinations thereof.

14. The coating of claim 1, wherein the implantable device is a stent.

15. The coating of claim 1, further comprising a bioactive agent 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, progenitor cell capturing antibody, prohealing drugs, prodrugs thereof, co-drugs thereof, and a combination thereof.

16. An implantable device formed of a composition that comprises:

a poly(ester amide) (PEA) polymer comprising a polymer chain having amide groups in the chain, and

a material for hydrogen-bonding with the PEA,

wherein the polymer chain of one molecule of the PEA polymer hydrogen-bonds to a molecule of the material for hydrogen-bonding, which in turn hydrogen-bonds to the polymer chain of another molecule of the PEA polymer.

17. The implantable device of claim 16, further comprising a bioactive agent 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, progenitor cell capturing antibody, prohealing drugs, prodrugs thereof, co-drugs thereof, and a combination thereof.

18. The implantable device of claim 16, which is a stent.