Stents having biodegradable layers

• US 9,737,642 B2
• Filed: 01/08/2008
• Issued: 08/22/2017
• Est. Priority Date: 01/08/2007
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, C. Douglas, Rabiner, Robert
• Primary Examiner(s): McDermott, Corrine
• Assistant Examiner(s): Ganesan, Suba
• Application Number:
  US12/522,379
• Publication Number:
  US 20100063580A1
• Time in Patent Office: 3,514 Days
• Field of Search: 623 115, 623 138, 623 144- 149, 623 142
• 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 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body

Abstract

A method for preparing a laminate coronary stent comprising: providing a stent framework; and depositing a plurality of layers on said stent framework to form said laminate coronary stent; wherein at least one of said layers comprises a bioabsorbable polymer.

Claims

1. A method of preparing a laminate coronary stent comprising:

a. providing a stent framework having a plurality of struts, each strut having a luminal, abluminal and side wall surfaces;

b. depositing a plurality of bioabsorbable polymer layers on the luminal, abluminal and side wall surfaces of each strut of said stent framework to form said laminate coronary stent;

c. depositing at least one active agent in crystalline form; and

d. sintering the stent after each polymer layer is deposited;

wherein said plurality of layers forms a coating on the stent framework, the coating consisting essentially of the bioabsorbable polymer and the active agent in crystalline form, and wherein at least one internal layer comprises the active agent; and

wherein the stent framework has a thickness of about 50% or less of a thickness of the laminate coronary stent.

2. The method of claim 1, wherein the stent framework is prepared by a method comprising laser cutting a tube;

lithographic transfer to a sheet and/or etching a previously prepared metal stent.

3. The method of claim 1, wherein the stent framework is prepared by a method comprising lithographic transfer to a bioabsorbable sheet.

4. The method of claim 1, wherein the stent framework is prepared by a method comprising etching a previously prepared metal stent made of absorbable material comprising magnesium.

5. The method of claim 1, wherein the stent framework is made of a bioabsorbable polymer or a conductive polymer.

6. The method of claim 1, wherein the stent framework is made of biocompatible non-bioabsorbable material.

7. The method of claim 1, wherein the stent framework is made of stainless steel.

8. The method of claim 1, wherein the stent framework has a thickness of about 1% or less of a thickness of the laminate coronary stent.

9. The method of claim 1, wherein said bioabsorbable polymer is selected from PGA poly(glycolide), LPLA poly(l-lactide), DLPLA poly(dl-lactide), PCL poly(ecaprolactone) PDQ, poly(dioxolane) PGA-TMC, 85115 DLPLG p(dl-lactide-co-glycolide), 75/25DLPLG, 65/35 DLPLG, 50/50 DLPLG, TMC poly(trimethylcarbonate), p(CPP:

SA) poly(1,3-bis-p(carboxyphenoxy)propane-co-sebacic acid).

10. The method of claim 1 comprising depositing 4, 10, 20, 50, 100 or more layers.

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

12. The method of claim 11, wherein the macrolide immunosuppressive drug comprises one or more of rapamycin, 40-O-(2-Hydroxyethyl)rapamycin (everolimus), 40-O-Benzyl-rapamycin, 40-O-(4′

-Hydroxymethyl)benzyl-rapamycin, 40-O-[4′

-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 40-O-Allyl-rapamycin, 40-O-[3′

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

-en-1′

-yl]-rapamycin, (2′

;

E,4′

S)-40-O-(4′

,5′

-Dihydroxypent-2′

-en-1′

-yl)-rapamycin, 40-O-(2-Hydroxy)ethoxycar-bonylmethyl-rapamycin, 40-O-(3-Hydroxy)propyl-rapamycin, 40-O-(6-Hydroxy)hexyl-rapamycin, 40-O-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin, 40-O-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 40-O-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 40-O-(2-Acetoxy)ethyl-rapamycin, 40-O-(2-Nicotinoyloxy)ethyl-rapamycin, 40-O-[2-(N-Morpholino)acetoxy]ethyl-rapamycin, 40-O-(2-N-Imidazolylacetoxy)ethyl-rapamycin, 40-O-[2-(N Methyl-N′

-piperazinyl)acetoxy]ethyl-rapamycin, 39-O-Desmethyl-39,40-O,O-ethylene-rapamycin, (26R)-26-Dihydro-40-O-(2-hydroxy)ethyl-rapamycin, 28-O-Methyl-rapamycin, 40-O-(2-Aminoethyl)-rapamycin, 40-O-(2-Acetaminoethyl)-rapamycin, 40-O-(2-Nicotinamidoethyl) rapamycin, 40-O-(2-(N-Methyl-imidazo-2′

-ylcarbethoxamido)ethyl)-rapamycin, 40-O-(2-Ethoxycarbonylaminoethyl)-rapamycin, 40-O-(2-Tolylsulfonamidoethyl)-rapamycin, 40-O-[2-(4′

,5′

Dicarboethoxy-1′

,2′

,3′

-triazol-1′

-yl)-ethyl]-rapamycin, 42-Epi-tetrazolyl)rapamycin (tacrolimus), and 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]rapamycin (temsirolimus).

13. The method of claim 11 further comprising depositing one or more active agents in dry powder form and sintering said plurality of layers under conditions that do not substantially modify the morphology of said one or more active agents.

14. A laminate coronary stent prepared by the method of claim 1.

15. A method of preparing a laminate coronary stent comprising:

a. providing a stent framework having a plurality of struts, each strut having a luminal, abluminal and side wall surfaces;

b. depositing a plurality of layers on the luminal, abluminal and side wall surfaces of each strut of said stent framework to form a coating, wherein forming the coating comprises the following steps;

i. discharging a crystalline pharmaceutical agent or an active biological agent in dry powder form through a first orifice;

ii. forming a supercritical or near supercritical fluid solution comprising at least one supercritical fluid solvent and a first polymer and discharging said supercritical or near supercritical fluid solution through said first orifice or through a second orifice under conditions sufficient to form solid particles of the first polymer;

iii. depositing the first polymer and the pharmaceutical agent or the active biological agent particles onto said framework, wherein an electrical potential is maintained between the framework and the first polymer and the pharmaceutical agent or the active biological agent particles;

iv. sintering the first polymer under conditions that do not substantially modify the morphology of the pharmaceutical agent or the activity of the biological agent;

V. forming a supercritical or near supercritical fluid solution comprising at least one supercritical fluid solvent and a second polymer and discharging said supercritical or near supercritical fluid solution through said first orifice or through a second orifice under conditions sufficient to form solid particles of the second polymer;

iii. depositing the second polymer onto said framework, wherein an electrical potential is maintained between the framework and the second polymer and the pharmaceutical agent or the active biological agent particles;

iv. sintering the second polymer under conditions that do not substantially modify the morphology of the pharmaceutical agent or the activity of the biological agent;

wherein the coating consists essentially of the first and second polymers and the pharmaceutical agent or the active biological agent, and wherein at least one internal layer comprises at least one pharmaceutical agent and/or active biological agent;

and the stent framework has a thickness of about 50% or less of a thickness of the laminate coronary stent.

16. The method of claim 15, wherein the first and second polymers are different.