Optimized drug-eluting stent assembly

• US 9,132,003 B2
• Filed: 06/25/2014
• Issued: 09/15/2015
• Est. Priority Date: 11/22/2006
• Status: Active Grant

• Current Assignee: InspireMD, Ltd.
• Original Assignee: InspireMD, Ltd.
• Inventors: Bar, Eli, Holzer, Asher, Paz, Ofir
• Primary Examiner(s): PELLEGRINO, BRIAN E
• Application Number:
  US14/314,777
• Publication Number:
  US 20140309725A1
• Time in Patent Office: 447 Days
• Field of Search: 623/1.13, 623/1.39, 623/1.4, 623/1.42, 623/1.43
• US Class Current: 1/1
• CPC Class Codes: A61F 2/0063 Implantable repair or support meshes, e.g. hernia meshes
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• 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 2002/0086 for preferentially controlling or promoting the growth of specific types of cells or tissues of bone tissue onto implantable joints A61F2002/3093
• CPC Class Codes: A61F 2002/075 the stent being loosely attached to the graft material, e.g. by stitching
• CPC Class Codes: A61F 2002/823 Stents, different from stent-grafts, adapted to cover an aneurysm
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0023 differing in porosity
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• 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 31/146 : Porous materials, e.g. foams or sponges
• 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: C08G 63/00 : Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule polyester-amides C08G69/44; polyester-imides C08G73/16
• CPC Class Codes: C08G 63/06 : derived from hydroxycarboxylic acids
• CPC Class Codes: C08G 63/08 : Lactones or lactides
• CPC Class Codes: C08G 63/40 : Polyesters derived from ester-forming derivatives of polycarboxylic acids or of polyhydroxy compounds, other than from esters thereof
• CPC Class Codes: C08G 73/02 : Polyamines
• CPC Class Codes: C08G 79/04 : Phosphorus linked to oxygen or to oxygen and carbon
• CPC Class Codes: Y10T 29/49964 : At least one part nonmetallic

Abstract

A stent assembly including a stent configured to be positioned in a body lumen, and a knitted stent jacket including an expansible mesh structure having a coverage area of less than 25%, having approximate aperture diameters greater than 20 micrometers, and surrounding an external surface of the stent and coaxially associated therewith, wherein the stent assembly elutes an amount of an active pharmaceutical agent.

Claims

1. A stent assembly, comprising:

a stent configured to be positioned in a body lumen; and

a knitted stent jacket comprising an expansible mesh structure disposed over a circumference of the stent and along an entire thereof, the mesh structure being formed from a single fiber and having a coverage area of about 9% to less than 25% relative to the coverage area of a plurality of apertures therein, the apertures having approximate aperture diameters greater than 20 micrometers up to a minimum center dimension of 234 micrometers and the knitted stent jacket being coaxially associated with the stent,

wherein the stent assembly elutes an amount of an active pharmaceutical agent that is present therein, and wherein the fiber has a diameter of approximately 7 micrometers to 40 micrometers.

2. The stent assembly of claim 1, wherein the active pharmaceutical agent is eluted from the stent.

3. The stent assembly of claim 1, wherein the active pharmaceutical agent is eluted from a coating disposed over a portion of the stent.

4. The stent assembly of claim 1, wherein the active pharmaceutical agent is time-released according to a predetermined treatment schedule.

5. The stent assembly of claim 4, wherein the treatment schedule covers a period of 8 hours to a plurality of months.

6. The stent assembly of claim 1, wherein the active pharmaceutical agent is eluted from the knitted stent jacket.

7. The stent assembly of claim 1, wherein the active pharmaceutical agent is eluted from a coating on the expansible mesh structure.

8. The stent assembly of claim 1, wherein the coaxial association comprises the knitted stent jacket being sewed, adhered, glued, folded, or sutured to the stent.

9. The stent assembly of claim 7, wherein the coaxial association is that the knitted stent jacket is sutured to the stent.

10. The stent assembly of claim 1, wherein a proximal portion of the knitted stent jacket is attached to a proximal portion of the stent.

11. The stent assembly of claim 10, wherein a distal portion of the stent jacket is attached to a distal portion of the stent.

12. The stent assembly of claim 7, wherein the amount of active pharmaceutical agent eluted comprises a therapeutically effective amount to treat a disorder in a carotid or coronary artery.

13. The stent assembly of claim 1, wherein the active pharmaceutical agent is eluted from the stent, a coating on the stent, the knitted stent jacket, a coating on the knitted stent jacket, or any combination thereof.

14. The stent assembly of claim 1, wherein the mesh structure is formed from a polymer component comprising one or more poly lactic-co-polyglycolic (“

PLGA”

), polycaprolactone (“

PCL”

), polygluconate, polylactic acid-polyethylene oxide, poly(hydroxybutyrate), polyanhydride, poly-phosphoester, poly(amino acids), poly-L-lactide, poly-D-lactide, polyglycolide, or poly(alpha-hydroxy acid) co-polymer(s), polyethylene terephthalate, or any combination thereof.

15. The stent assembly of claim 13, wherein the mesh structure comprises a single polymer fiber.

16. The stent assembly of claim 15, wherein the polymer is elastic, biocompatible, and hemocompatible.

17. The stent assembly of claim 1, wherein the expansible mesh structure comprises a retracted state and a deployed state, and further wherein the expansible mesh structure defines apertures having a minimum center dimension of 150 micrometers to 200 micrometers in the deployed state.

18. The stent assembly of claim 1, wherein the expansible mesh structure comprises a retracted state and a deployed state, and further wherein the expansible mesh structure defines apertures having a minimum center dimension of 150 micrometers to 180 micrometers in the deployed state.

19. The stent assembly of claim 1, wherein the active pharmaceutical agent comprises zolimus, zotarolimus, sirolimus, taxol/paclitaxel, or a combination thereof.

20. The stent assembly of claim 1, wherein the active pharmaceutical agent comprises an anti-proliferative agent, an antithrombotic agent, an anticoagulant, an antioxidant, a growth factor inhibitor, a collagen inhibitor, a liposome, a steroid or corticosteroid, a statin, endothelial cell seeds, a hydrogel containing endothelial cells, or a combination thereof.

21. The stent assembly of claim 20, wherein the anti-proliferative agent is present and comprises sirolimus, zolimus or zotarolimus, a taxane, tacrolimus, everolimus, vincritine, viblastine, a HMG-CoA reductase inhibitor, doxorubicin, colchicine, actinomycin D, mitomycin C, cycloporine, mycophenolic acid, triazolopyrimidine, or a combination thereof;

wherein the antithrombotic agent is present and comprises heparin, a heparin-like dextran derivative, acid citrate dextrose, coumadin, warfarin, streptokinase, anistreplase, tissue plasminogen activator (tPA), urokinase, abciximab, or a combination thereof;

wherein the growth factor inhibitor is present and comprises tranilast, angiopeptin, or a combination thereof;

wherein the steroid or corticosteroid is present and comprises cortisone, prednisolone, or both;

wherein the statin is present and comprises simvastatin, lovastatin, or a combination thereof;

or any combination of the foregoing.

22. The stent assembly of claim 1, wherein the stent assembly comprises 1 microgram to 200 micrograms of each pharmaceutical agent.

23. The stent assembly of claim 1, wherein the mesh of the knitted stent jacket comprises 1 microgram to 200 micrograms of each pharmaceutical agent.

24. The stent assembly of claim 1, wherein the active pharmaceutical agent comprises a '"'"'limus drug at a concentration of 10 μ

g/mm² to 80 μ

g/mm².

25. The stent assembly of claim 1, wherein the active pharmaceutical agent comprises a '"'"'limus drug at a concentration of 80 μ

g/mm² to 140 μ

g/mm².

26. The stent assembly of claim 2, wherein the stent comprises a metal alloy coated with a biodegradable polymer, biostable polymer, bioresorbable polymer, or a combination thereof.

27. The stent assembly of claim 1, wherein the stent comprises a biodegradable material.

28. The stent assembly of claim 27, wherein the biodegradable material comprises a polymer.

29. The stent assembly of claim 27, wherein the biodegradable material comprises a metal alloy.