Stents having biodegradable layers

• US 10,617,795 B2
• Filed: 06/27/2017
• Issued: 04/14/2020
• Est. Priority Date: 01/08/2007
• Status: Active Grant

• Current Assignee: Micell Medtech Incorporated
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Charles Douglas, Rabiner, Robert
• Primary Examiner(s): Ganesan, Suba
• Application Number:
  US15/634,246
• Publication Number:
  US 20180000996A1
• Time in Patent Office: 1,022 Days
• 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;

b. depositing a plurality of bioabsorbable polymer layers on said stent framework to form said laminate coronary stent;

c. sintering the stent after each polymer layer is deposited; and

d. depositing at least one active agent in crystalline form,

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 includes a plurality of struts, each strut having a luminal abluminal and side wall surfaces, and wherein the polymer depositing steps include depositing the bioabsorbable polymer on the luminal, abluminal and sidewall surfaces.

3. The method of claim 1, wherein the depositing steps form a coating on the stent framework, the coating consisting essentially of the bioabsorbable polymer and the active agent in crystalline form.

4. The method of claim 1, further comprising the step of laser cutting, lithographic transferring or etching a substrate to create the stent framework.

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(e caprolactone) PDQ, poly(dioxolane) PGA-TMC, 85115 DLPLG p(dl-lactide-co-glycolide), 75/25 DLPLG, 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, wherein the polymer depositing includes depositing 4, 10, 20, 50, 100 or more polymer 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, 40-0-(2-Hydroxyethyl)rapamycin (everolimus), 40-0-Benzyl-rapamycin, 40-0-(4′

-Hydroxymethyl)benzyl-rapamycin, 40-0-[4′

-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 40-0-Allyl-rapamycin, 40-0-[3′

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

-en-1′

-yl]-rapamycin, (2′

;

E,4′

S)-40-0-(4′

,5′

-Dihydroxypent-2′

-en-1′

-yl)-rapamycin, 40-0-(2-Hydroxy)ethoxycar-bonylmethyl-rapamycin, 40-0-(3-Hydroxy)propyl-rapamycin, 40-0-(6-Hydroxy)hexyl-rapamycin, 40-0-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin, 40-0-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 40-0-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 40-0-(2-Acetoxy)ethyl-rapamycin, 40-0-(2-Nicotinoyloxy)ethyl-rapamycin, 40-0-[2-(N-Morpholino)acetoxyl ethyl-rapamycin, 40-0-(2-N-Imidazolylacetoxy)ethyl-rapamycin, 40-0-[2-(N Methyl-N′

-piperazinyl)acetoxy]ethyl-rapamycin, 39-0-Desmethyl-39,40-0,0-ethylene-rapamycin, (26R)-26-Dihydro-40-0-(2-hydroxy)ethyl-rapamycin, 28-0-Methyl-rapamycin, 40-0-(2-Aminoethyl)-rapamycin, 40-0-(2-Acetaminoethyl)-rapamycin, 40-0-(2-Nicotinamidoethyl) rapamycin, 40-0-(2-(N-Methyl-imidazo-2′

-ylcarbethoxamido)ethyl)-rapamycin, 40-0-(2-Ethoxycarbonylaminoethyl)-rapamycin, 40-0-(2-Tolylsulfonamidoethyl)-rapamycin, 40-0-[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. A laminate coronary stent prepared by the method of claim 1.

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

a. depositing a plurality of bioabsorbable polymer layers on a stent framework;

b. sintering the stent after each polymer layer is deposited; and

c. depositing at least active agent in crystalline form,

wherein the polymer layers and active agent form a coating on the stent framework and the stent framework has a thickness of about 50% or less of a thickness of the laminate coronary stent.

15. The method of claim 14, wherein the stent framework includes a plurality of struts, each strut having a luminal abluminal and side wall surfaces, and wherein the polymer depositing steps include depositing the bioabsorbable polymer on the luminal, abluminal and sidewall surfaces.

16. The method of claim 14, wherein the depositing steps form a coating on the stent framework, the coating consisting essentially of the bioabsorbable polymer and the active agent in crystalline form.

17. The method of claim 16, wherein said bioabsorbable polymer is selected from PGA poly(glycolide), LPLA poly(l-lactide), DLPLA poly(dl-lactide), PCL poly(e caprolactone) PDQ, poly(dioxolane) PGA-TMC, 85115 DLPLG p(dl-lactide-co-glycolide), 75/25 DLPLG, 65/35 DLPLG, 50/50 DLPLG, TMC poly(trimethylcarbonate), p(CPP:

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

18. The method of claim 16, wherein the active agent comprises one or more of rapamycin, 40-0-(2-Hydroxyethyl)rapamycin (everolimus), 40-0-Benzyl-rapamycin, 40-0-(4′

-Hydroxymethyl)benzyl-rapamycin, 40-0-[4′

-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 40-0-Allyl-rapamycin, 40-0-[3′

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

-en-1′

-yl]-rapamycin, (2′

;

E,4′

S)-40-0-(4′

,5′

-Dihydroxypent-2′

-en-1′

-yl)-rapamycin, 40-0-(2-Hydroxy)ethoxycarbonylmethyl-rapamycin, 40-0-(3-Hydroxy)propyl-rapamycin, 40-0-(6-Hydroxy)hexyl-rapamycin, 40-0-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin, 40-0-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 40-0-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 40-0-(2-Acetoxy)ethyl-rapamycin, 40-0-(2-Nicotinoyloxy)ethyl-rapamycin, 40-0-(2-(N-Morpholino)acetoxy]ethyl-rapamycin, 40-0-(2-N-Imidazolylacetoxy)ethyl-rapamycin, 40-0-[2-(N Methyl-N′

-piperazinyl)acetoxy]ethyl-rapamycin, 39-0-Desmethyl-39,40-0,0-ethylene-rapamycin, (26R)-26-Dihydro-40-0-(2-hydroxy)ethyl-rapamycin, 28-0-Methyl-rapamycin, 40-0-(2-Aminoethyl)-rapamycin, 40-0-(2-Acetaminoethyl)-rapamycin, 40-0-(2-Nicotinamidoethyl) rapamycin, 40-0-(2-(N-Methyl-imidazo-2′

-ylcarbethoxamido)ethyl)-rapamycin, 40-0-(2-Ethoxycarbonylaminoethyl)-rapamycin, 40-0-(2-Tolylsulfonamidoethyl)-rapamycin, 40-0-[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).