Blends of poly(ester amide) polymers

• US 7,520,891 B2
• Filed: 03/26/2008
• Issued: 04/21/2009
• Est. Priority Date: 10/06/2004
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Kleiner, Lothar W., Pacetti, Stephen Dirk, DesNoyer, Jessica R.
• Primary Examiner(s): WOODWARD, ANA LUCRECIA
• Application Number:
  US12/056,197
• Publication Number:
  US 20080177008A1
• Time in Patent Office: 391 Days
• Field of Search: 424/94.1, 424/94.3, 424/94.4, 424/423, 424/426, 424/486, 424/501, 525/425, 525/432, 525/436, 525/437, 525/444, 623/1.15, 623/1.46
• US Class Current: 623/1.15
• CPC Class Codes: A61L 2300/606 Coatings
• 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 2666/14 Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C08L 77/12 Polyester-amides

Abstract

Provided herein is a poly(ester amide) (PEA) polymer blend and a polymeric coating containing the PEA polymer blend. The PEA polymer blend has a T_g above the T_g of poly(ester amide benzyl ester) (PEA-Bz) or the T_g of poly(ester amide TEMPO). 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 polymeric coating for an implantable device, comprising a drug and a poly(ester amide) (PEA) polymer blend having a glass transition temperature (T_g) above the T_g of poly(ester amide benzyl ester) (PEA-Bz) or poly{[N,N′

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

-sebacoyl-L-lysine 2,2,6,6-tetramethyl-4-amino-1-piperidinyloxyl amide]} (PEA-TEMPO), comprising;

a first PEA polymer having a T_g equal to or below the T_g of PEA-Bz or T_g of PEA-TEMPO, and

a second PEA polymer having a T_g above the T_g of PEA-Bz or T_g of PEA-TEMPO.

2. The coating of claim 1, wherein the PEA polymer blend comprises a PEA polymer of any of formulae 3-7:

-[-sebacinate-L-Leu-hexanediol-L-Leu-]_n- 

 

Formula 3

-[-adipate-L-Leu-hexanediol-L-Leu-]_n- 

 

Formula 4A

-[-sebacinate-L-Leu-butanediol-L-Leu-]_n- 

 

Formula 4B

-[-adipate-L-Leu-butanediol-L-Leu-]_n- 

 

Formula 4C

-[-sebacinate-L-Val-hexanediol-L-Val-]_n- 

 

Formula 5A

-[-sebacinate-L-Phe-hexanediol-L-Phe-]_n- 

 

Formula 5B

-[-adipate-L-Val-butanediol-L-Val-]_n- 

 

Formula 5C

-[-adipate-L-Phe-butanediol-L-Phe-]_n- 

 

Formula 5D

-[-adipate-L-Leu-hexanediol-L-Leu-]_m-[-adipate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6A

-[-sebacinate-L-Leu-butanediol-L-Leu-]_m-[-sebacinate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6B

-[-adipate-L-Leu-butanediol-L-Leu-]_m-[-adipate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6C

-[-sebacinate-L-Val-hexanediol-L-Val-]_m-[-sebacinate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6D

-[-sebacinate-L-Phe-hexanediol-L-Phe-]_m-[sebacinate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6E

-[-adipate-L-Val-butanediol-L-Val-]_m-[-adipate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6F

-[-adipate-L-Phe-butanediol-L-Phe-]_m-[-adipate-Lys-R]_n—

R=benzyl ester or TEMPO 

 

Formula 6G

-[-sebacinate-L-Leu-hexanediol-L-Leu-]_m-[-sebacinate-Lys R]_n—

R=methyl, ethyl, or propyl 

 

Formula 7

wherein m and n are independent positive integers ranging from 1 to 100,000.

3. The polymer coating of claim 1, wherein the PEA polymer blend has an effective T_g of about or above 37°

C.

4. The polymer coating of claim 1, wherein the first PEA polymer or the second PEA polymer comprises unit(s) derived from at least one unnatural amino acid.

5. The polymer coating of claim 1, wherein the first PEA polymer or the second PEA polymer comprises unit(s) derived from two amino acids.

6. The polymer coating of claim 1, wherein the device is a stent.

7. The polymer coating of claim 1, wherein the drug is selected from the group consisting of paclitaxel, docetaxel, estradiol, 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, 40-O-tetrazole-rapamycin (ABT-578), clobetasol, and a combination thereof.

8. The polymer coating of claim 1, wherein the is everolimus.

9. The polymer coating of claim 1, wherein the drug is selected from the group consisting of a nitric oxide donor, a super oxide dismutase, a super oxide dismutase mimic, and combinations thereof.