STENTS HAVING BIODEGRADABLE LAYERS

• US 20100211164A1
• Filed: 04/17/2008
• Published: 08/19/2010
• Est. Priority Date: 04/17/2007
• Status: Abandoned Application

• Current Assignee: Micell Technologies Inc.
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Douglas
• Application Number:
  US12/595,848
• Publication Number:
  US 20100211164A1
• Time in Patent Office: Days
• US Class Current: 623/1.460
• 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 2230/0069 cylindrical
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 2300/608 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 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/10 Macromolecular materials
• 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: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Provided herein is a coated coronary stent, comprising: a. stent framework; b. a plurality of layers deposited on said stent framework 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

1-98. -98. (canceled)

99. A coated stent comprising

a. a stent framework;

b. a plurality of layers deposited on said stent framework to form said coated 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.

100. The stent of claim 99, wherein at least one of said layers comprises a PLGA bioabsorbable polymer and at least one of said layers comprises rapamycin;

wherein at least part of rapamycin is in crystalline form.

101. The coated stent of claim 100, wherein said rapamycin is at least 50% crystalline.

102. The coated stent of claim 100, wherein said rapamycin is at least 90% crystalline.

103. The stent of claim 100, wherein the rapamycin and polymer are in the same layer;

in separate layers or form overlapping layers.

104. The coronary stent of claim 100, wherein the plurality of layers comprise five layers deposited as follows:

a first polymer layer, a first rapamycin layer, a second polymer layer, a second rapamycin layer and a third polymer layer.

105. The stent of claim 104, wherein the stent framework is formed from a material comprising the following percentages by weight:

0.05-0.15 C, 1.00-2.00 Mn, 0.040 Si, 0.030 P, 0.3 S, 19.00-21.00 Cr, 9.00-11.00 Ni, 14.00-16.00 W, 3.00 Fe, and Bal. Co.

106. The stent of claim 104, wherein the stent framework is formed from a material comprising at most the following percentages by weight:

about 0.025 maximum C, 0.15 maximum Mn, 0.15 maximum Si, 0.015 maximum P, 0.01 maximum S, 19.00-21.00 maximum Cr, 33-37 Ni, 9.0-10.5 Mo, 1.0 maximum Fe, 1.0 maximum Ti, and Bal. Co

107. The stent of claim 104, wherein the drug layers are substantially free of polymer and the polymer layers are substantially free of drug.

108. The stent of claim 99, wherein said bioabsorbable polymer is selected from PGA poly(glycolide), LPLA poly(l-lactide), DLPLA poly(dl-lactide), PCL poly(e-caprolactone) PDO, poly(dioxolane) PGA-TMC, 85/15 DLPLG p(dl-lactide-co-glycolide), 75/25 DLPL, 65/35 DLPLG, 50/50 DLPLG, TMC poly(trimethylcarbonate), p(CPP:

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

109. A method of preparing a coated stent comprising:

a. providing a stent framework;

b. depositing a plurality of layers on said stent framework to form said coated stent;

wherein at least one of said layers comprises a bioabsorbable polymer;

wherein depositing each layer of said plurality of layers on said stent framework comprises the following steps;

discharging at least one pharmaceutical agent and/or at least one active biological agent in dry powder form though a first orifice;

discharging the at least one polymer in dry powder form through said first orifice or through a second orifice;

depositing the polymer and pharmaceutical agent and/or active biological agent particles onto said framework, wherein an electrical potential is maintained between the framework and the polymer and pharmaceutical agent and/or active biological agent particles, thereby forming said layer; and

sintering said layer under conditions that do not substantially modify the morphology of said pharmaceutical agent and/or the activity of said biological agent.

112. The method of claim 109, further comprising discharging a third dry powder comprising a second pharmaceutical agent in a therapeutically desirable morphology in dry powder form and/or active biological agent whereby a layer comprising at least two different pharmaceutical agents and/or active biological agents is deposited on said framework or at least two layers each comprising one of two different pharmaceutical agents and/or active biological agents are deposited on said framework.

113. The method of claim 109, wherein the framework is electrostatically charged.

114. The method of claim 109, wherein at least 50% of said pharmaceutical agent in powder form is crystalline or semicrystalline.

115. The method of claim 109, wherein said bioabsorbable polymer is selected from PGA poly(glycolide), LPLA poly(l-lactide), DLPLA poly(dl-lactide), PCL poly(e-caprolactone) PDO, poly(dioxolane) PGA-TMC, 85/15 DLPLG p(dl-lactide-co-glycolide), 75/25 DLPL, 65/35 DLPLG, 50/50 DLPLG, TMC poly(trimethylcarbonate), p(CPP:

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

116. The method of claim 109, comprising depositing 4, 10, 20, 50, or 100 layers.

117. The method of claim 109, wherein said layers comprise alternate drug and polymer layers.

118. The method of claim 117, wherein the drug layers are substantially free of polymer and the polymer layers are substantially free of drug.

110. A method of preparing a coronary stent comprising:

a. providing a stent framework;

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

wherein at least one of said layers comprises a bioabsorbable polymer;

at least one pharmaceutical agent in a therapeutically desirable morphology and/or at least one active biological agent;

wherein depositing each layer of said plurality of layers on said stent framework comprises the following steps;

i. discharging the at least one pharmaceutical agent and/or at least one 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 at least one polymer and discharging said supercritical or near supercritical fluid solution through a second orifice under conditions sufficient to form solid particles of the polymer;

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

iv. sintering said layer under conditions that do not substantially modify the morphology of said pharmaceutical agent and/or the activity of said biological agent.

111. A method of preparing a coronary stent comprising:

a. providing a stent framework;

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

wherein at least one of said layers comprises a bioabsorbable polymer;

at least one pharmaceutical agent in a therapeutically desirable morphology and/or at least one active biological agent;

wherein depositing each layer of said plurality of layers on said stent framework comprises the following steps;

i. forming a supercritical or near supercritical fluid solution comprising at least one supercritical fluid solvent and one or more pharmaceutical agents and/or at least one active biological agent discharging said supercritical or near supercritical fluid solution through a first orifice under conditions sufficient to form solid particles of said one or more pharmaceutical agents and/or at least one active biological agent;

ii. forming a supercritical or near supercritical fluid solution comprising at least one supercritical fluid solvent and at least one 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 polymer;

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

iv. sintering said layer under conditions that do not substantially modify the morphology of said pharmaceutical agent and/or the activity of said biological agent.