Stents having biodegradable layers
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.
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).