PERIPHERAL STENTS HAVING LAYERS

• US 20150030757A1
• Filed: 08/12/2014
• Published: 01/29/2015
• Est. Priority Date: 03/23/2009
• Status: Abandoned Application

• Current Assignee: Micell Technologies Inc.
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Douglas
• Application Number:
  US14/457,609
• Publication Number:
  US 20150030757A1
• Time in Patent Office: Days
• US Class Current: 427/2.21
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/001 for adjusting a diameter
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• 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 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

Provided herein is a coated coronary stent, comprising: a. stent; b. a plurality of layers deposited on said stent to form said coronary stent; wherein at least one of said layers comprises a bioabsorbable polymer and at least one of said layers comprises one or more active agents; wherein at least part of the active agent is in crystalline form.

Claims

1. A method for preparing a coated stent comprising the following steps:

providing a stent;

forming a coating comprising a pharmaceutical agent and a polymer on the stent wherein at least part of the pharmaceutical agent is in crystalline form, wherein forming the coating comprises depositing a fiber reinforcement on the stent, wherein the length of the fiber is up to 5 micrometers, and wherein the coating is substantially resistant to stent strut breakage.

2. The method of claim 1, wherein the fiber reinforcement is a natural fiber.

3. The method of claim 1, wherein the fiber reinforcement is a synthetic fiber.

4. The method of claim 1, wherein the fiber reinforcement is deposited on the stent by a Rapid Expansion of Supercritical Solutions (RESS) process.

5. The method of claim 1, wherein the fiber reinforcement is deposited on the stent in dry form.

6. The method of claim 1, wherein the length of the fiber is 200 nanometers to 5 micrometers.

7. The method of claim 1, wherein the fiber comprises a length to diameter ratio of 3:

1.

8. The method of claim 1, wherein forming the coating comprises depositing at least one of the pharmaceutical agent and the polymer in dry powder form.

9. The method of claim 8, wherein forming the coating comprises depositing a plurality of layers on said stent to form said coated stent.

10. The method of claim 9, wherein the plurality of layers comprises at least one polymer layer and at least one pharmaceutical agent layer.

11. The method of claim 10, wherein the fiber reinforcement is part of the polymer layer.

12. The method of claim 10, wherein the fiber reinforcement is part of the pharmaceutical agent layer.

13. The method of claim 10, wherein forming the coating comprises depositing alternate pharmaceutical agent and polymer layers.

14. The method of claim 1, wherein the polymer comprises at least one bioabsorbable polymer.

15. The method of claim 14, wherein the bioabsorbable polymer is selected from PLGA (poly(lactide-co-glycolide);

DLPLA—

poly(dl-lactide);

LPLA—

poly(1-lactide);

PGA—

polyglycolide;

PDO—

poly(dioxanone);

PGA-TMC—

poly(glycolide-co-trimethylene carbonate);

PGA-LPLA—

poly(1-lactide-co-glycolide);

PGA-DLPLA—

poly(dl-lactide-co-glycolide);

LPLA-DLPLA—

poly(1-lactide-co-dl-lactide);

PDO-PGA-TMC—

poly(glycolide-co-trimethylene carbonate-co-dioxanone) and combinations thereof.

16. The method of claim 1, wherein the pharmaceutical agent comprises a macrolide immunosuppressive (limus) drug.

17. The method of claim 16, wherein the macrolide immunosuppressive drug comprises one or more of rapamycin, 4O—

O-(2-Hydroxyethyl)rapamycin (everolimus), 4O—

O-Benzyl-rapamycin, 4O—

O-(4′

-Hydroxymethyl)benzyl-rapamycin, 4O—

O-[4′

-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 4O—

O-Allyl-rapamycin, 4O—

O-[3′

-(2,2-Dimethyl-1,3-dioxolan-4(S)-yl)-prop-2′

-en-1′

-yl]-rapamycin, (2′

;

E,4′

S)-4O—

O-(4′

,5′

-Dihydroxypent-2′

-en-1′

-yl)-rapamycin, 4O—

O-(2-Hydroxy)ethoxycar-bonylmethyl-rapamycin, 4O—

O-(3-Hydroxy)propyl-rapamycin, 4O—

O-(6-Hydroxy)hexyl-rapamycin, 4O-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin, 4O—

O-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 4O—

O-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 4O—

O-(2-Acetoxy)ethyl-rapamycin, 4O—

O-(2-Nicotinoyloxy)ethyl-rapamycin, 4O—

O-[2-(N-Morpholino)acetoxy]ethyl-rapamycin, 4O—

O-(2-N-Imidazolylacetoxy)ethyl-rapamycin, 4O—

O-[2-(N-Methyl-N′

-piperazinyl)acetoxy]ethyl-rapamycin, 39-O-Desmethyl-39,40-O,O-ethylene-rapamycin, (26R)-26-Dihydro-4O—

O-(2-hydroxy)ethyl-rapamycin, 28-O-Methyl-rapamycin, 4O—

O-(2-Aminoethyl)-rapamycin, 4O—

O-(2-Acetaminoethyl)-rapamycin, 4O—

O-(2-Nicotinamidoethyl)-rapamycin, 4O—

O-(2-(N-Methyl-imidazo-2′

-ylcarbethoxamido)ethyl)-rapamycin, 4O-(2-Ethoxycarbonylaminoethylkapamycin, 4O—

O-(2-Tolylsulfonamidoethyl)-rapamycin, 4O—

O-[2-(4′

,5′

-Dicarboethoxy-1′

,2′

,3′

-triazol-1′

-yl)-ethyl]-rapamycin, 42-Epi-(tetrazolyl)rapamycin (tacrolimus), 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]rapamycin (temsirolimus), and 4O-epi-(N-1-tetrazolyl)-rapamycin (zotarolimus).

18. The method of claim 1, comprising forming a silane layer on the stent, and covalently attaching heparin to the silane layer.

19. The method of claim 18, wherein onset of heparin anti-coagulant activity is obtained at week 3 or later, and wherein heparin anti-coagulant activity remains at an effective level for at least one of:

90 days after onset of heparin activity, at least 120 days after onset of heparin activity, at least 200 days after onset of heparin activity.

20. The method of claim 8, wherein the forming coating is done when the stent is in a collapsed state.

21. The method of claim 8, wherein said coated stent has a radial expansion ratio of about 1 in a collapsed state and at least one of:

up to about 3.0 in the expanded state, up to about 3.0 in the expanded state, up to about 4.0 in the expanded state, up to about 5.0 in the expanded state, up to about 6.0 in the expanded state, over about 3.0 in the expanded state, and over about 4.0 in the expanded state.