Blends of poly(ester amide) polymers

• US 20070093617A1
• Filed: 12/12/2006
• Published: 04/26/2007
• Est. Priority Date: 10/06/2004
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen, DesNoyer, Jessica, Kleiner, Lothar
• Granted Patent: US 7,365,133 B2
• Time in Patent Office: Days
• US Class Current: 525/425
• 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 coatings and medical devices formed of the blend.

Claims

1. 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,

wherein the first PEA polymer or the second PEA polymer comprises unit(s) derived from at least one unnatural amino acid.

2. The PEA polymer blend of claim 1, having an effective T_g of equal to or above 37°

C.

3. The PEA polymer blend of claim 1, further comprising a non-PEA biocompatible polymer.

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

5. A PEA polymer blend, comprising a PEA polymer and a non-PEA biocompatible polymer having a T_g above the T_g of PEA-Bz or the T_g of PEA-TEMPO, wherein the PEA polymer comprises unit(s) derived from at least one unnatural amino acid.

6. The PEA polymer blend of claim 6, wherein the non-PEA biocompatible polymer is selected from the group consisting of 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(L-lactide), poly(D,L-lactide), poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(phospho esters), poly(trimethylene carbonate), poly(oxaesters), poly(oxaamides), poly(ethylene carbonate), poly(propylene carbonate), poly(phosphoesters), poly(phosphazenes), poly(tyrosine derived carbonates), poly(tyrosine derived arylates), poly(tyrosine derived iminocarbonates), copolymers thereof with poly(ethylene glycol), and combinations thereof.

7. A bioabsorbable implantable device comprising 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), the PEA polymer blend 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.

8. The bioabsorbable implantable device of claim 7, wherein the PEA polymer blend has an effective T_g of equal to or above 37°

C.

9. The bioabsorbable implantable device of claim 7, wherein the PEA polymer blend further comprises a non-PEA biocompatible polymer.

10. The bioabsorbable implantable device of claim 7, wherein the first PEA polymer or the second PEA polymer comprises unit(s) derived from two amino acids.

11. The bioabsorbable implantable device of claim 7, 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—

 

 

Formula 6A

R=benzyl ester or TEMPO

—

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

 

 

Formula 6B

R=benzyl ester or TEMPO

—

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

 

 

Formula 6C

R=benzyl ester or TEMPO

—

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

 

 

Formula 6D

R=benzyl ester or TEMPO

—

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

 

 

Formula 6E

R=benzyl ester or TEMPO

—

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

 

 

Formula 6F

R=benzyl ester or TEMPO

—

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

 

 

Formula 6G

R=benzyl ester or TEMPO

—

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

 

 

Formula 7

R=methyl, ethyl, or propyl

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

12. The bioabsorbable implantable device of claim 7, which is a stent.

15. The bioabsorbable implantable device of claim 7, further comprising a bioactive agent.

17. The bioabsorbable implantable device of claim 15, 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, dexamnethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamnycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rap amycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, progenitor cell capturing antibody, prohealing drugs, prodrugs thereof, co-drugs thereof, and a combination thereof.

19. A method of treating a disorder in a patient comprising implanting in the patient an implantable device comprising the polymeric coating of claim 17, 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.

13. A bioabsorbable implantable device comprising a PEA polymer blend, the PEA polymer blend comprising a PEA polymer and a non-PEA biocompatible polymer having a T_g above the T_g of PEA-Bz or the T_g of PEA-TEMPO, wherein the PEA polymer comprises unit(s) derived from at least one unnatural amino acid.

14. The bioabsorbable implantable devcie of claim 13, wherein the non-PEA biocompatible polymer is selected from 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(L-lactide), poly(D,L-lactide), poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolide), poly(D,L-lactide-co-glycolide), poly(phospho esters), poly(trimethylene carbonate), poly(oxaesters), poly(oxaamides), poly(ethylene carbonate), poly(propylene carbonate), poly(phosphoesters), poly(phosphazenes), poly(tyrosine derived carbonates), poly(tyrosine derived arylates), poly(tyrosine derived iminocarbonates), copolymers thereof with poly(ethylene glycol), and combinations thereof.

16. The bioabsorbable implantable device of claim 13, further comprising a bioactive agent.

18. The bioabsorbable implantable device of claim 16, wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase 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-rapaamycin, and 40-O-tetrazole-rapamycin, ABT-578, clobetasol, progenitor cell capturing antibody, prohealing drugs, prodrugs thereof, co-drugs thereof, and a combination thereof.

20. A method of treating a disorder in a patient comprising implanting in the patient an implantable device comprising the polymeric coating of claim 18, 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.