IMPLANTABLE DEVICE HAVING A SLOW DISSOLVING POLYMER

• US 20090110711A1
• Filed: 10/31/2007
• Published: 04/30/2009
• Est. Priority Date: 10/31/2007
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: TROLLSAS, MIKAEL O., Sherman, David J., Hossainy, Syed F.A., Ngo, Michael H.
• Granted Patent: US 8,642,062 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 31/33 Heterocyclic compounds
• 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: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/446 Superoxide dismutase (1.15)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5089 Processes
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 71/02 : Polyalkylene oxides

Abstract

The present invention provides an implantable device having a coating including a slow dissolving polymer or material and the methods of making and using the same.

Claims

1. An implantable device, comprising a coating deposited thereon that comprises a polymer derived from lactide (LA), glycolide (GA), and poly(ethylene glycol) (PEG),

wherein the LA is D,L-lactide (DLLA), L-lactide (LLA), D-lactide (DLA), meso-lactide (mLA) or combinations thereof,

wherein the polymer has a weight average molecular weight (Mw) from about 50 KD to about 200 KD and comprises:

a content of GA from about 10% to about 50% by weight; and

a content of PEG from about 5% to about 50% by weight, and

wherein the coating is capable of fully absorbed within 12 months upon exposure to a physiological environment.

2. The implantable device of claim 1, wherein the polymer has a molecular weight of about 100 KD or above.

3. The implantable device of claim 1, wherein the polymer comprises a block selected from poly(DLLA-co-GA), poly(LLA-co-GA), poly(DLA-co-GA), or poly(mLA-co-GA).

4. The implantable device of claim 3, wherein the block has a LA/GA ratio from about 99/1 to about 1/99.

5. The implantable device of claim 3, wherein the block has a LA/GA ratio from about 90/10 to about 10/90.

6. The implantable device of claim 3, wherein the block has a LA/GA ratio from about 70/30 to about 30/70.

7. The implantable device of claim 1, wherein the content of PEG is about 20-80% by weight.

8. The implantable device of claim 1, wherein the content of PEG is about 30% or about 40% by weight.

9. The implantable device of claim 1, wherein the polymer breaks into fragments upon exposure of the coating to a physiological environment.

10. The implantable device of claim 1, wherein the coating further comprises a bioactive agent.

11. The implantable device of claim 10, wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, 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, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, feno fibrate, prodrugs thereof, co-drugs thereof, and combinations thereof.

12. The implantable device of claim 1, which is a stent.

13. The implantable device of claim 1, which is a bioabsorbable stent.

25. A method, comprising implanting in a patient an implantable device according to claim 1, 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, patent foramen ovale, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, and combinations thereof.

14. A method, comprising depositing a coating over the implantable device, the coating comprising a polymer derived from lactide (LA), glycolide (GA), and poly(ethylene glycol) (PEG),

wherein the LA is D,L-lactide (DLLA), L-lactide (LLA), D-lactide (DLA), meso-lactide (mLA) or combinations thereof,

wherein the polymer has a weight average molecular weight (Mw) from about 50 KD to about 200 KD and comprises:

a content of GA from about 10% to about 50% by weight; and

a content of PEG from about 5% to about 50% by weight, and

wherein the coating is capable of fully absorbed within 12 months upon exposure to a physiological environment.

15. The method of claim 14, wherein the polymer has a molecular weight of about 50 KD or above.

16. The method of claim 14, wherein the polymer comprises a block selected from poly(DLLA-co-GA), poly(LLA-co-GA), poly(DLA-co-GA), or poly(mLA-co-GA).

17. The method of claim 16, wherein the block has a LA/GA ratio from about 99/1 to about 1/99.

18. The method of claim 16, wherein the block has a LA/GA ratio from about 90/10 to about 10/90.

19. The method of claim 16, wherein the block has a LA/GA ratio from about 70/30 to about 30/70.

20. The method of claim 14, wherein the content of PEG is about 20-80% by weight.

21. The method of claim 14, wherein the content of PEG is about 30% or about 40% by weight.

22. The method of claim 14, wherein the polymer breaks into fragments upon exposure of the coating to a physiological environment.

23. The method of claim 14, wherein the polymeric matrix further comprises a bioactive agent.

24. The method of claim 23, wherein the bioactive agent is selected from paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus, 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, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, feno fibrate, prodrugs thereof, co-drugs thereof, and combinations thereof.