Bioabsorbable medical device with coating

• US 7,959,942 B2
• Filed: 10/20/2007
• Issued: 06/14/2011
• Est. Priority Date: 10/20/2006
• Status: Active Grant

• Current Assignee: OrbusNeich Medical Pte Ltd
• Original Assignee: Orbusneich Medical Incorporated (Orbusneich Medical)
• Inventors: Cottone, Robert J.
• Primary Examiner(s): Saoud; Christine J
• Assistant Examiner(s): Seharaseyon; Jegatheesan
• Application Number:
  US11/875,887
• Publication Number:
  US 20080097575A1
• Time in Patent Office: 1,333 Days
• Field of Search: None
• US Class Current: 424/428
• CPC Class Codes: A61F 2/844 folded prior to deployment
• CPC Class Codes: A61F 2/88 the wire-like elements formed as helical or spiral coils forming a net-like or mesh-like structure A61F2/90
• CPC Class Codes: A61F 2/89 the wire-like elements comprising two or more adjacent rings flexibly connected by separate members
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2220/0016 with sharp anchoring protrusions, e.g. barbs, pins, spikes
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2400/16 Materials with shape-memory or superelastic properties
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/042 : Polysaccharides
• CPC Class Codes: A61L 31/044 : Collagen
• CPC Class Codes: A61L 31/046 : Fibrin; Fibrinogen
• CPC Class Codes: A61L 31/047 : Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• 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 31/125 : having a macromolecular matrix
• 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 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A biodegradable, bioabsorbable medical device with a coating for capturing progenitor endothelial cells in vivo and delivering a therapeutic agent at the site of implantation. The coating on the medical device is provided with a biabsorbable polymer composition such as a bioabsorbable polymer, copolymer, or terpolymer, and a copolymer or terpolymer additive for controlling the rate of delivery of the therapeutic agent.

Claims

1. An implantable medical device, comprising a crystallized bioabsorbable polymer scaffold and a coating;

said crystallized bioabsorbable polymer scaffold comprising, at least about 70% (w/w) of a base polymer comprising a poly (L-lactide) moiety, and/or a poly (D-lactide) moiety, and/or poly L-lactide-co-PEG moiety, and/or poly D-lactide-co PEG moiety, linked with a modifying copolymer comprising poly (L-lactide-co-Tri-methylene-carbonate) or poly (D-lactide-co-tri-methylene-carbonate) or poly (L-lactide-co-ε

-caprolactone) or poly (D-lactide-co-ε

-caprolactone) in the form of block copolymers or blocky random copolymers; and

said coating comprising a bioabsorbable matrix and a ligand.

2. The implantable medical device of claim 1 wherein said ligand is configured to bind target cells in vivo.

3. The implantable medical device of claim 1 wherein said ligand is a small molecule, a peptide, an antibody, antibody fragments, or combinations thereof and the target cell is a progenitor endothelial cell antigen.

4. The implantable medical device of claim 1 wherein said coating comprises one or more layers.

5. The implantable medical device of claim 1 wherein said matrix comprises a naturally occurring or synthetic biodegradable polymer.

6. The implantable medical device of claim 5 wherein said matrix comprises at least one of the group consisting of:

tropoelastin, elastin, laminin, fibronectin, fibrin, collagen, basement membrane proteins, and cross-linked tropoelastin.

7. The implantable medical device of claim 4 wherein at least one coating layer, or the implantable medical device itself, comprises a radioopaque or radio-detectable material.

8. The implantable medical device of claim 1 wherein said implantable medical device is impregnated with a pharmacological or biological substance.

9. The implantable medical device of claim 1 comprising a tube defining a lumen, said tube having an outer surface and an inner surface, said inner surface surrounding said lumen.

10. The implantable medical device of claim 9 wherein said outer surface is coated with a composition comprising a pharmacological substance.

11. The implantable medical device of claim 9 wherein said outer or inner surface is coated with a composition comprising a biological substance.

12. The implantable medical device of claim 8 or 10 wherein said pharmacological substance is at least one of the group consisting of:

cyclosporin A, mycophenolic acid, mycophenolate mofetil acid, rapamycin, rapamycin derivatives, biolimus A9, CCI-779, RAD 001, AP23573, azathioprene, pimecrolimus, tacrolimus (FK506), tranilast, dexamethasone, corticosteroid, everolimus, retinoic acid, vitamin E, rosglitazone, simvastatins, fluvastatin, estrogen, 17.beta.-estradiol, hydrocortisone, acetaminophen, ibuprofen, naproxen, fluticasone, clobetasol, adalimumab, sulindac, dihydroepiandrosterone, testosterone, puerarin, platelet factor 4, basic fibroblast growth factor, fibronectin, butyric acid, butyric acid derivatives, paclitaxel, paclitaxel derivatives, LBM-642, deforolimus, and probucol.

13. The implantable medical device of claim 11 wherein said biological substance is at least one of the group consisting of:

antibiotics/antimicrobials, antiproliferative agents, antineoplastic agents, antioxidants, endothelial cell growth factors, smooth muscle cell growth and/or migration inhibitors, thrombin inhibitors, immunosuppressive agents, anti-platelet aggregation agents, collagen synthesis inhibitors, therapeutic antibodies, nitric oxide donors, antisense oligonucleotides, wound healing agents, therapeutic gene transfer constructs, peptides, proteins, extracelluar matrix components, vasodialators, thrombolytics, anti-metabolites, growth factor agonists, antimitotics, steroids, steroidal antiinflammatory agents, chemokines, proliferator-activated receptor-gamma agonists, proliferator-activated receptor-alpha agonists proliferator-activated receptor-beta agonists, proliferator-activated receptor-alpha/beta agonists, proliferator-activated receptor-delta agonists, NF.kappa.beta., proliferator-activated receptor-alpha-gamma agonists, nonsterodial antiinflammatory agents, angiotensin converting enzyme(ACE) inhibitors, free radical scavangers, inhibitors of the CX3CR1 receptor and anti-cancer chemotherapeutic agents.

14. The implantable medical device of claim 1, the crystallized bioabsorbable polymer scaffold comprises a base polymer of from about 70% by weight of poly (L-lactide) with 30% by weight of modifying copolymer poly L-lactice-co-TMC.

20. The implantable medical device of claim 1, wherein said medical device comprises a bioabsorbable implant having a tissue contacting surface and a fluid contacting surface, said implant comprising a bioabsorbable, biocompatible first coating for controlled release of one or more pharmaceutical substances from said tissue contacting surface, and a second coating comprising one or more ligands which bind to specific molecules on cell membranes of progenitor endothelial cells on the fluid contacting surface of the medical device.

21. The bioabsorbable implant of claim 20, wherein the medical device is a stent, a vascular or other synthetic graft, or a stent in combination with a synthetic graft.

22. The bioabsorbable implant of claim 20, wherein the medical device is a vascular stent.

23. The bioabsorbable implant of claim 20, wherein the tissue contacting surface coating comprises poly(DL-lactide-co-glycolide) and one or more pharmaceutical substances.

24. The bioabsorbable implant of claim 20, wherein the tissue contacting surface coating comprises poly(DL-lactide), or poly(lactide-co-glycolide), and paclitaxel.

25. The bioabsorbable implant of claim 20, wherein the pharmaceutical substance is at least one of the group consisting of antibiotics/antimicrobials, antiproliferative agents, antineoplastic agents, antioxidants, endothelial cell growth factors, smooth muscle cell growth and/or migration inhibitors, thrombin inhibitors, immunosuppressive agents, anti-platelet aggregation agents, collagen synthesis inhibitors, therapeutic antibodies, nitric oxide donors, antisense oligonucleotides, wound healing agents, therapeutic gene transfer constructs, peptides, proteins, extracellular matrix components, vasodialators, thrombolytics, anti-metabolites, growth factor agonists, antimitotics, steroids, steroidal antiinflammatory agents, chemokines, proliferator-activated receptor-gamma agonists, proliferator-activated receptor-alpha-gamma agonists, proliferator-activated receptor-alpha agonists, proliferator-activated receptor-beta agonists, proliferator-activated receptor-alpha/beta agonists, proliferator-activated receptor-delta agonists, NF.kappa.beta., nonsterodial antiinflammatory agents, angiotensin converting enzyme(ACE) inhibitors, free radical scavangers, inhibitors of the CX3CR1 receptor, and anti-cancer chemotherapeutic agents.

26. The bioabsorbable implant of claim 20, wherein the pharmaceutical substance is selected from the group consisting of cyclosporin A, mycophenolic acid, mycophenolate mofetil acid, rapamycin, rapamycin derivatives, biolimus A9, CCI-779, RAD 001, AP23573, azathioprene, pimecrolimus, tacrolimus (FK506), tranilast, dexamethasone, corticosteroid, everolimus, retinoic acid, vitamin E, rosglitazone, simvastatins, fluvastatin, estrogen, 17.beta.-estradiol, hydrocortisone, acetaminophen, ibuprofen, naproxen, fluticasone, clobetasol, adalimumab, sulindac, dihydroepiandrosterone, testosterone, puerarin, platelet factor 4, basic fibroblast growth factor, fibronectin, butyric acid, butyric acid derivatives, paclitaxel, paclitaxel derivatives, LBM-642, deforolimus, and probucol.

27. The bioabsorbable implant of claim 24, wherein the poly(DL-lactide) polymer comprises from about 50 to about 99% of the composition.

28. The bioabsorbable implant of claim 20, wherein either or both coatings comprise multiple layers of the poly(DL-lactide) polymer, poly(lactide-co-glycolide) copolymer, or mixture thereof.

29. The bioabsorbable implant of claim 20, wherein the either or both coatings comprise multiple layers of the pharmaceutical substances.

15. A bioabsorbable implant comprising:

a crystallized bioabsorbable polymer scaffold comprising at least about 70% (w/w) of a base polymer comprising a poly (L-lactide) moiety, and/or a poly (D-lactide) moiety, and/or poly L-lactide-co-PEG moiety, and/or poly D-lactide-co PEG moiety, linked with a modifying copolymer comprising poly (L-lactide-co-Tri-methylene-carbonate) or poly (D-lactide-co-tri-methylene-carbonate) or poly (L-lactide-co-ε

-caprolactone) or poly (D-lactide-co-ε

-caprolactone) in the form of block copolymers or blocky random copolymers; and

a ligand.

16. The bioabsorbable implant of claim 15, wherein the base polymer is 70% by weight of poly L-lactide with 30% by weight of modifying copolymer poly L-lactice-co-TMC.

17. The bioabsorbable implant of claim 15, wherein the ligand comprises a small molecule, a peptide, an antibody, antibody fragments, or combinations thereof and the target cell is a progenitor endothelial cell.

18. The bioabsorbable implant of claim 17, wherein the antibody or antibody fragments is specific for binding a progenitor endothelial cell membrane antigen.

19. The bioabsorbable implant of claim 18, wherein the progenitor endothelial cell membrane antigen is selected from the group consisting of CD34, CD45, CD133, CD14, CDw90, CD117, HLA-DR, VEGFR-1, VEGFR-2, CD146, CD130, CD131, stem cell antigen, stem cell factor 1, Tie-2, MCH-H-2Kk and MCH-HLA-DR.