Poly(ester amide) block copolymers

• US 20060142541A1
• Filed: 12/27/2004
• Published: 06/29/2006
• Est. Priority Date: 12/27/2004
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Hossainy, Syed Faiyaz Ahmed
• Granted Patent: US 7,419,504 B2
• Time in Patent Office: Days
• US Class Current: 528/354
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: C08G 69/44 Polyester-amides
• CPC Class Codes: C08L 77/12 Polyester-amides

Abstract

Provided herein is a copolymer that includes a soft block (A) that contains poly(ester amide) (PEA) and a hard block (B). The copolymer can be any of AB, ABA or BAB type block copolymers. By varying the relative amount of the PEA block and the hard block, one can obtain a copolymer with a T_g for mechanical integrity in drug-delivery stent applications. The copolymer can be used alone or optionally in combination with a biobeneficial material and/or a biocompatible polymer to form an implantable device or a coating on an implantable device. When the copolymer is used in combination with a biobeneficial material, the copolymer and the biobeneficial material can be co-deposited or applied in sequence during the coating process. A coating formed of the copolymer may also include a bioactive agent. The implantable device can be implanted in a patient to treat, prevent, or ameliorate 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, and/or tumor obstruction.

Claims

1. A copolymer comprising a soft block (A) that comprises poly(ester amide) (PEA) and a hard block (B), wherein the hard block comprises a block derived from a polymer selected from the group consisting of poly(D,L-lactic acid) (PDLLA, polyglycolic acid (PGA), poly(D,L-lactic acid-co-glycolic acid) (PDLLG), glycerol-sebacic acid, polytyrosine carbonate, polytyrosine, tyrosine oligomer, or tyrosine di-peptide, poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(3-hydroxyvalerate) (PHV), polyphosphazene, and combinations thereof.

2. The block copolymer of claim 1, wherein the soft block is selected from the group consisting of PEA, PEA-PEG, or a combination thereof.

3. The block copolymer of claim 2, wherein the hard block comprises functional groups.

4. The block copolymer of claim 1 wherein the hard block comprises tyrosine di-peptide.

6. The copolymer of claim 4, wherein the tyrosine di-peptide can be wherein the tyrosine di-peptide block is

racemic tyrosine di-peptide, desamine tyrosyl tyrosine di-peptide, desamine tyrosyl-tyrosine di-peptide, desamino tyrosyl-tyrosine hexyl ester (DTH), desamino tyrosyl-tyrosine palmityl ester (DTP), n-benzyloxycarbonyl-tyrosyl-tyrosine hexyl ester (z-TTH), or combinations thereof.

7. The polymer of claim 1, which is an AB, ABA or BAB type block copolymer.

8. A polymeric composition comprising a moiety derived from the polymer of claim 4 and a moiety derived from a compound having the structure of

wherein X can be (1) an organic moiety R₁, provided that R₁ has one or more halo groups such as iodo or bromo groups, (2) halo groups such as iodo or bromo groups, or (3) combinations thereof,

wherein R and R₁ taken independently can be any chemical grouping having one or more reactive groups capable of conjugating to the carboxyl group or amino group of the tyrosine di-peptide block, the reactive groups being selected from the group consisting of carboxyl groups, aldehyde groups, amino groups, alcohol, ester, thiol, PEG, leaving groups, mesylate and tosylate, and

wherein n is a positive integer between 1 and 3.

9. A coating on an implantable device comprising the copolymer of claim 1 and optionally a bioactive agent.

11. The coating of claim 9 further comprising a biobeneficial material.

13. The coating of claim 9 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, progenitor cell capturing antibody, prohealing drugs, prodrugs thereof, co-drugs thereof, and a combination thereof.

14. An absorbable stent formed of a material comprising the copolymer of claim 1.

16. The stent of claim 14, further comprising a biobeneficial material.

18. The stent of claim 14, further comprises a bioactive agent.

20. A method of treating, preventing, or ameliorating a disorder in a patient comprising implanting in the patient an implantable device comprising the coating of claim 9, 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.

22. A method of treating, preventing, or ameliorating a disorder in a patient comprising implanting in the patient the implantable device of claim 14, 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.

5. A copolymer comprising a poly(ester amide) block and a tyrosine di-peptide block.

10. A coating on an implantable device comprising the copolymer of claim 5 and optionally a bioactive agent.

12. The coating of claim 10 further comprising a biobeneficial material.

15. An absorbable stent formed of a material comprising the copolymer of claim 5.

17. The stent of claim 15, further comprising a biobeneficial material.

19. The stent of claim 15, further comprises a bioactive agent.

21. A method of treating, preventing, or ameliorating a disorder in a patient comprising implanting in the patient an implantable device comprising the coating of claim 10, 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.

23. A method of treating, preventing, or ameliorating a disorder in a patient comprising implanting in the patient the implantable device of claim 15, 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.