Amorphous poly(D,L-lactide) coating

• US 8,778,375 B2
• Filed: 04/29/2005
• Issued: 07/15/2014
• Est. Priority Date: 04/29/2005
• Status: Active Grant

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Pacetti, Stephen D., Hossainy, Syed Faiyaz Ahmed, Gale, David C.
• Primary Examiner(s): WESTERBERG, NISSA M
• Application Number:
  US11/117,813
• Publication Number:
  US 20060246108A1
• Time in Patent Office: 3,364 Days
• Field of Search: None
• US Class Current: 424/423
• 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: 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: C08L 101/00 Compositions of unspecified macromolecular compounds
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C09D 167/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C09D167/06 takes precedence

Abstract

Implantable devices formed of or coated with a material that includes an amorphous poly(D,L-lactide) formed of a starting material such as meso-D,L-lactide are provided. The implantable device can be used for the treatment, mitigation, prevention, or inhibition of a disorder such as 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, or combinations thereof.

Claims

1. A coating comprising an amorphous poly(D,L-lactide) (PDLLA) having a degree of crystallinity of 10% or below and an additional biocompatible polymer,

wherein the PDLLA is not made from a 50/50 blend of L,L-lactide and D,D-lactide,

wherein the amorphous PDLLA is poly(meso-D,L-lactide) (meso-DLPLA), racemic poly(D,L-lactide) (racemic-DLPLA), or combination thereof,

wherein the coating further comprises a syndiotactic polylactide (LPLA),

and wherein the additional biocompatible polymer is selected from the group consisting of polymers and copolymers of 3-hydroxypropanoate, 3-hydroxyhexanoate, 3-hydroxyheptanoate, 3-hydroxyoctanoate, 4-hydroxyhexanote, 4-hydroxyheptanoate, and 4-hydroxyoctanoate;

poly(tyrosine carbonates);

poly(tyrosine ester);

polyphosphoester;

polyphosphoester urethane;

polycyanoacrylates;

poly(vinylidene fluoride-co-hexafluoropropylene);

cellulose butyrate;

phosphoryl choline;

poly(aspirin);

polymers and co-polymers of alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA);

poly(styrene-isoprene-styrene)-PEG (SIS-PEG);

polystyrene-PEG;

polyisobutylene-PEG;

polycaprolactone-PEG (PCL-PEG);

poly(methyl methacrylate)-PEG (PMMA-PEG);

polydimethylsiloxane-co-PEG (PDMS-PEG);

polypropylene oxide-co-polyethylene glycol;

poly(tetramethylene glycol);

hydroxy functional poly(vinyl pyrrolidone); and

combinations thereof.

2. The coating of claim 1, wherein the amorphous PDLLA has a degree of crystallinity of about or below 1%.

3. The coating of claim 1, wherein the additional biocompatible polymer is biodegradable.

4. A stent comprising the coating of claim 1.

5. A stent comprising the coating of claim 3.

6. A stent comprising the coating of claim 2.

7. The stent of claim 4, wherein the coating further comprises a biobeneficial material, and

wherein the additional biocompatible polymer is biodegradable.

8. The stent of claim 7, wherein the biobeneficial material is selected from the group consisting of poly(ethylene glycol), poly(alkylene oxides), phosphoryl choline, 2-methacyloyloxyethylphosphoryl choline, poly(vinyl pyrrolidone), poly(styrene sulfonate), NO-donor polymers, hyaluronic acid, fibrin, albumin, elastin, dextran, dextrin, polysaccharides, heparin, fullerenes, and a combination thereof.

9. The stent of claim 4, further comprising a bioactive agent.

10. The stent of claim 5, further comprising a bioactive agent.

11. The stent 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, 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, pimecrolimus, imatinib mesylate, midostaurin, clobetasol, and a combination thereof.

12. The stent of claim 10, 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, 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, pimecrolimus, imatinib mesylate, midostaurin, clobetasol, and a combination thereof.

16. A method of treatment of a disorder in a patient comprising implanting in the patient a stent 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, patent foramen ovale, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, and combinations thereof.

20. The coating of claim 3, wherein the additional biocompatible polymer is selected from the group consisting of poly(vinylidene fluoride-co-hexafluoropropylene);

phosphoryl choline;

poly(tetramethylene glycol); and

combinations thereof.

21. The stent of claim 7, wherein the biobeneficial material is selected from the group consisting of albumin, a block copolymer having poly(ethylene glycol) and poly(butylene terephthalate) blocks, and combinations thereof.

22. The coating of claim 1, wherein the additional biocompatible polymer is selected from the group consisting of polymers and copolymers of 3-hydroxypropanoate, 3-hydroxyhexanoate, 3-hydroxyheptanoate, 3-hydroxyoctanoate, 4-hydroxyhexanote, 4-hydroxyheptanoate, and 4-hydroxyoctanoate;

poly(tyrosine carbonates);

polyphosphoester;

polycyanoacrylates;

poly(vinylidene fluoride-co-hexafluoropropylene);

cellulose butyrate;

phosphoryl choline;

poly(aspirin);

polymers and co-polymers of alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA);

poly(styrene-isoprene-styrene)-PEG (SIS-PEG);

polystyrene-PEG;

polyisobutylene-PEG;

polycaprolactone-PEG (PCL-PEG);

poly(methyl methacrylate)-PEG (PMMA-PEG); and

combinations thereof.

23. The stent of claim 4, wherein the additional biocompatible polymer is selected from the group consisting of polymers and copolymers of 3-hydroxypropanoate, 3-hydroxyhexanoate, 3-hydroxyheptanoate, 3-hydroxyoctanoate, 4-hydroxyhexanote, 4-hydroxyheptanoate, and 4-hydroxyoctanoate;

poly(tyrosine carbonates);

polyphosphoester;

polycyanoacrylates;

poly(vinylidene fluoride-co-hexafluoropropylene);

cellulose butyrate;

phosphoryl choline;

poly(aspirin);

polymers and co-polymers of alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA);

poly(styrene-isoprene-styrene)-PEG (SIS-PEG);

polystyrene-PEG;

polyisobutylene-PEG;

polycaprolactone-PEG (PCL-PEG);

poly(methyl methacrylate)-PEG (PMMA-PEG); and

combinations thereof.

24. The stent of claim 21, wherein the biobeneficial material is a block copolymer having poly(ethylene glycol) and poly(butylene terephthalate) blocks.

13. An absorbable stent formed of a material comprising an amorphous poly(D,L-lactide) (PDLLA) having a degree of crystallinity of about or below 10% and an additional biocompatible polymer,

wherein the PDLLA is not made from a 50/50 blend of L,L-lactide and D,D-lactide,

wherein the amorphous PDLLA is poly(meso-D,L-lactide) (meso-DLPLA), racemic poly(D,L-lactide) (racemic-DLPLA), or combination thereof,

wherein the material further comprises a syndiotactic polylactide (LPLA), and

wherein the additional biocompatible polymer is selected from the group consisting of polymers and copolymers of 3-hydroxypropanoate, 3-hydroxyhexanoate, 3-hydroxyheptanoate, 3-hydroxyoctanoate, 4-hydroxyhexanote, 4-hydroxyheptanoate, and 4-hydroxyoctanoate;

poly(tyrosine carbonates);

poly(tyrosine ester);

polyphosphoester;

polyphosphoester urethane;

polycyanoacrylates;

poly(vinylidene fluoride-co-hexafluoropropylene);

cellulose butyrate;

phosphoryl choline;

poly(aspirin);

polymers and co-polymers of alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA);

poly(styrene-isoprene-styrene)-PEG (SIS-PEG);

polystyrene-PEG;

polyisobutylene-PEG;

polycaprolactone-PEG (PCL-PEG);

poly(methyl methacrylate)-PEG (PMMA-PEG);

polydimethylsiloxane-co-PEG (PDMS-PEG);

polypropylene oxide-co-polyethylene glycol;

poly(tetramethylene glycol);

hydroxy functional poly(vinyl pyrrolidone); and

combinations thereof.

14. The absorbable stent of claim 13, further comprising a biobeneficial material and/or a bioactive agent.

15. The absorbable stent of claim 13, further comprising a biobeneficial material and a bioactive agent.

17. A method of treating a disorder in a patient comprising implanting in the patient an absorbable stent of claim 13, 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.

18. An implantable device comprising a coating that comprises:

alternating layers comprising meso-DLPLA and comprising racemic-DLPLA;

wherein one layer is a primer layer consisting of meso-DLPLA and a syndiotactic polylactide (LPLA).

19. An implantable device comprising a coating that comprises:

alternating layers comprising meso-DLPLA and comprising syndiotactic polylactide (LPLA);

wherein one layer is a primer layer consisting of meso-DLPLA and a syndiotactic polylactide (LPLA).