JP2004089233A - Stent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a stent having the releasability of a bioactive chemical stable for a long period of time and stability inside the body and capable of controlling the releasing amount and speed of the bioactive chemical. <P>SOLUTION: For the stent (1), a primer layer (P), a chemical holding layer (M) and a coating layer (12) are coated in this order on the surface of a stent base material (11). The chemical holding layer (M) is composed of a water absorptive high polymer material containing the bioactive chemical, which releases the bioactive chemical inside a living body and absorbs water ≥100% of the dead weight at least. The primer layer (P) is composed of a material highly compatible to both of the stent base material (11) and the water absorptive high polymer material constituting the chemical holding layer (M), and the coating layer (12) is composed of a high polymer material capable of coating the chemical holding layer (M). <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an improvement of a stent which can be implanted in a blood vessel or a body cavity and is used for treatment of a stenosis, and in particular, is coated with a polymer material containing a biologically active substance to have antithrombotic properties and intimal proliferation. The present invention relates to a stent that provides a surface for restraint or the like and prevents restenosis.
[0002]
[Prior art]
A stent is a tubular medical device that is placed in a blood vessel or another lumen in a living body when the stenosis or occlusion is obstructed or occluded in order to expand the stenosis or the like and secure a necessary lumen area. The stent is inserted into the body with a small diameter, expanded at a stenosis or the like, and used to expand and hold the lumen by increasing the diameter.
[0003]
For example, in recent years, for the purpose of reconstruction of a stenotic blood vessel, a percutaneous coronary angioplasty (hereinafter referred to as PTCA: Percutaneous Transluminal Angioplasty) is used to perform treatment by dilatation with a PTCA balloon catheter and placement of a stent. ing. The stent is intended to prevent / suppress restenosis by sending air to a balloon attached to a catheter and placing the stent in a blood vessel formed by inflation / expansion.
As described above, stent placement has been performed with the expectation of suppressing restenosis for angioplasty by only balloon dilatation, but in fact, the restenosis rate was higher than expected at the beginning. At present, no reduction has been obtained.
This is considered to be one of the causes of inducing formation of thrombus and proliferation of smooth muscle due to vascular damage caused by the stent itself when the stent is expanded and deployed.
[0004]
For this reason, conventionally, in catheters and the like, attempts have been made to incorporate or bind these drugs such as anticoagulants in the polymer constituting the catheter tube and to gradually release these drugs locally. However, in the case of a stent, since the base material is usually a metal, it is difficult to apply a technique such as directly bonding or impregnating the base material to the base material as has been mainly performed with a catheter. Therefore, as for the stent, the only applicable method is a method in which the drug is dissolved and mixed in an organic solvent together with the polymer and applied.
[0005]
In the first place, heparin and urokinase, which are typical bioactive substances known to be antithrombotic, are practically insoluble in organic solvents, so that the above method is practically impossible. . Further, conventionally, a stent coated with a coating layer made of a polymer material containing an anticoagulant or an antiplatelet agent such as aspirin or argatroban alone or in combination or a stent wound with a film made of the polymer material is known. (See, for example, JP-A-8-224297 and JP-A-8-33718).
[0006]
[Problems to be solved by the invention]
An object of the present invention is to improve a polymer coating layer (drug holding layer) in a stent for suppressing restenosis by sustained release of a drug, thereby improving the amount of water-soluble drug retained in the polymer material and the sustained release property. It is an object of the present invention to provide a technique that enables the stent to be stably used in the body for a longer period of time without exfoliation or the like.
[0007]
[Means for Solving the Problems]
According to the present invention, the following inventions are provided.
[1] The present invention provides a stent (1) in which the surface of a stent substrate (11) is coated in the order of a primer layer (P) / a drug holding layer (M) / a coating layer (12).
[2] In the present invention, the drug holding layer (M) is made of a water-absorbing polymer material that contains a bioactive agent, gradually releases the bioactive agent in vivo, and absorbs at least 100% of its own weight of water. ,
The primer layer (P) is made of a material having a high affinity for both the stent base material (11) and the water-absorbing polymer material constituting the drug holding layer (M),
The covering layer (12) provides a stent (1) made of a polymer material capable of covering the drug holding layer (M).
[0008]
[3] The present invention provides the stent (1) according to [1] or [2], wherein the water-absorbing polymer material constituting the drug holding layer (M) is a polyether-based polyurethane.
[4] The present invention provides the stent (1) according to any one of [1] to [3], wherein the polymer material covering the drug holding layer (M) is a polycarbonate-based polyurethane.
[5] The present invention provides the stent (1) according to any one of [1] to [4], wherein the primer layer (P) is a silane coupling agent having a hydrolyzable group and an organic functional group.
[6] The present invention provides the stent (1) according to any one of [1] to [5], wherein the primer layer (P) is a cyanoacrylate-based adhesive.
[0009]
[7] The present invention provides a method for producing a stent (1) including the following steps.
(1) a step of coating the surface of the stent substrate (11) with a primer layer (P);
(2) a step of coating the surface of the primer layer (P) with a drug holding layer (M);
(3) a step of coating the surface of the drug holding layer (M) with a coating layer (12);
[8] The present invention provides a drug holding layer by applying or dipping a solution in which a water-absorbing polymer material is dissolved on the surface of a stent substrate (11) coated with a primer layer (P) to volatilize a solvent. (M) is formed, the stent base material (11) is immersed in an aqueous solution of a bioactive agent for a predetermined time, and then dried to introduce the bioactive agent into the drug holding layer (M) [7]. A method for producing the described stent (1) is provided.
[0010]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described in detail.
The stent 1 of the present invention is a stent 1 in which the surface of a stent base material 11 is coated in the order of a primer layer P / a drug holding layer M / a coating layer 12.
The drug holding layer M is made of a water-absorbing polymer material which contains a bioactive agent, releases the bioactive agent in vivo, and absorbs at least 100% of its own weight of water.
The primer layer P is made of a material having a high affinity for both the stent base material 11 and the water-absorbing polymer material constituting the drug holding layer M.
The coating layer 12 is made of a polymer material that can cover the medicine holding layer M.
In the present invention, in forming the drug holding layer M on the stent base material 11, first, a high affinity primer for both the stent base material 11 and the water-absorbing polymer material forming the drug holding layer M, The surface of the stent substrate 11 is treated to form a primer layer P.
Next, a solution in which the water-absorbing polymer material is dissolved is prepared, and the solution is applied or immersed on the surface 11 of the stent base material on which the primer layer P is formed to volatilize the solvent, thereby forming the drug holding layer M. Can be.
In order to introduce a water-soluble drug into the drug holding layer M, the stent substrate 11 on which the drug holding layer M is formed is immersed in a desired physiologically active drug aqueous solution for an arbitrary time and then dried. Can be introduced. Further, the drug holding layer M is covered with a coating layer 12 made of a polymer material. Thus, three coating layers (primer layer P / drug holding layer M / coating layer 12) are formed on the stent substrate 11. The stent 1 itself has a four-layer structure including the stent base material 11.
[0011]
FIG. 1 is a schematic view showing an example of a stent 1 of the present invention, and FIG. 2 is a partially enlarged cross-sectional view of FIG. 1. The stent 1 includes a stent substrate 11 including a stent substrate 11, a primer layer P, and a drug. This is an example in which a four-layer structure of a holding layer M and a coating layer 12 is formed.
The material constituting the base material 11 of the stent may be a material known per se, and is not particularly limited. For example, a stainless steel such as SUS316L, a shape memory alloy such as a Ti-Ni alloy, a Cu-Al-Mn alloy, etc. , Titanium, titanium alloy, tantalum, tantalum alloy, platinum, platinum alloy, tungsten, tungsten alloy, etc. A stitch-like substantially tubular body formed by the above method is used. The shape of the substantially tubular body is not particularly limited as long as desired physical properties can be obtained.
[0012]
In addition, the drug holding layer M used in the present invention is formed of a water-absorbing polymer material containing at least 100% or more of its own weight of water, which contains at least a physiologically active agent and can release the physiologically active agent in vivo. You.
In the present invention, as the water-absorbing polymer material, for example, known starch-polyacrylonitrile hydrolyzate, starch-polyacrylate crosslinked product, crosslinked carboxymethylcellulose, saponified vinyl acetate-methyl acrylate copolymer, polyacrylic Sodium acid cross-linked products, cross-linked polyvinyl alcohol, and polyacrylamide-based materials, of which materials having a water absorption of 100 times or more of their own weight can be used. As the conductive polymer material, a water-absorbing polymer material that is soluble in an organic solvent and can be coated on the stent, and at least does not peel off in accordance with the expansion of the stent, but can be followed, is preferred, and a polypropylene oxide chain, polytetramethylene Polyether chains such as oxide chains in the structure Urethane elastomers and gels or gel-like water absorbent polymer material based on them are preferred.
[0013]
The water-absorbing polymer material that can be used in the present invention is not limited to those listed above, and does not dissolve in water, blood, or saline, and efficiently contains a water-soluble bioactive agent. For this purpose, water can contain 100% or more of its own weight (the same amount or more as its own weight), and an effective amount of the bioactive agent is gradually eluted from the surface through the coating layer 12 in the living body (sustained release). ) Can be used, and any material having the above characteristics can be used.
[0014]
As a material of the coating layer 12, a sustained release over a certain period of time can be achieved by controlling the type (material) and thickness of the coating layer 12 without inhibiting the release of the bioactive agent from the drug holding layer M as a stent. Polyether-based, polycarbonate-based polyurethane, polyester, polyether polyamide, and the like are preferable because they are easily maintained. More specifically, unlike a medical device that performs a temporary treatment or placement such as a catheter, an intravascular stent to be placed in a blood vessel is placed semipermanently in a body (implant). Polycarbonate polyurethane having high hydrolyzability is most preferable as the material of the coating layer 12 of the intravascular stent of the present invention.
[0015]
As will be described later, the water-absorbing polymer material constituting the drug holding layer M is applied to the stent base material 11 and dried. In the present invention, the stent base material 11 and the stent base material 11 are coated. It is important that the primer layer P is formed on the stent base material 11 by performing a pretreatment in advance with a primer having a high affinity for both of the water-absorbing polymer materials.
That is, the surface of the stent base material 11 is first treated with a primer having an affinity for both the constituent material (metal) of the stent base material 11 and the water-absorbing polymer material to form a primer layer P, Then, after coating with a water-absorbing polymer material to form a drug holding layer M, the stent base material 11 is immersed in an aqueous solution of a bioactive agent for a predetermined time, and then dried to dry the bioactive agent into the drug holding layer. M, and then a coating layer 12 made of a polymer material is formed.
[0016]
In the present invention, various primers can be used as the primer, but most preferably a silane coupling agent having a hydrolyzable group and an organic functional group.
The hydrolyzable group (for example, alkoxy group) of the silane coupling agent forms a silanol group and is bonded to the metallic stent base by a covalent bond or the like, while the organic functional group (for example, epoxy group, amino group, mercapto group) is formed. Group, vinyl group, methacryloxy, etc.) is chemically bonded to a water-absorbing polymer material containing a physiologically active agent, whereby the water-absorbing polymer material and the stent base material 11 are connected via a silane coupling agent. It is much tighter than when it is not used. Here, an epoxy-based silane coupling agent having an epoxy group as an organic functional group is particularly preferred, but an amino-based or mercapto-based silane coupling agent having the same performance can also be suitably used. .
[0017]
As the silane coupling agent, an appropriate one having an organic functional group corresponding thereto may be selected depending on the type of the resin of the water-absorbing polymer material to be used. For example, the following can be suitably used. That is, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropyldimethoxysilane, 2- (3,4-epoxycyclohexyl) ethyltrimethoxysilane, vinyltriethoxysilane, 3-methacryloxypropyltrimethoxysilane, N-2 (aminoethyl) 3-aminopropylmethyldimethoxysilane, N-2 (aminoethyl) 3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-mercaptopropyltrimethoxysilane, N-phenyl- 3-Aminopropyltrimethoxysilane 3-chloropropyltrimethoxysilane and the like are preferably used.
[0018]
In addition, as the primer, in addition to the silane coupling agent, organic titanium-based cups such as tetrabutoxytitanate, tetrastearyl titanate, tetraisopropoxytitanate, isopropoxytitanium stearate, and titanium lactate having the same function as this. A coupling agent; an aluminum-based coupling agent such as acetoalkoxyaluminum diisopropylate; a chromium-based coupling agent; and an organic phosphoric acid-based coupling agent can also be appropriately used.
[0019]
A primer such as a silane coupling agent having an affinity for both the constituent material (metal) of the stent base material 11 and the water-absorbing polymer material is usually water, a suitable organic solvent, or water and an organic solvent. A pretreatment is performed by dissolving this in a mixed solvent of the above and applying and drying this as a treatment solution on the substrate surface. The organic solvent is not particularly limited, but, for example, methanol, ethanol, isopropanol, a mixed solvent of the alcohol and water, benzene, toluene, xylene and the like are preferably used. As the primer concentration in the treatment solution, a relatively dilute solution is used, and is 0.05 to 2% by mass, preferably 0.1 to 1.0% by mass.
[0020]
In the present invention, by performing such a primer treatment (forming the primer layer P) on the stent base material 11 before coating the water-absorbing polymer material, the stability of the coating of the water-absorbing polymer material is improved. The resulting stent is placed in the body, and is placed in the body for a period sufficient to form an intima, for example, when buried in a blood vessel, for example, for at least one month. Even in this case, the coating layer (drug holding layer M, coating layer 12) can be stably maintained in a water (physiological saline solution, phosphate buffer solution) environment without any peeling or the like. Action and effect can be obtained. In this regard, when the water-absorbing polymer material is directly applied to the metal constituting the stent base material, depending on the conditions, the coating layer (drug holding layer M) can be formed in a water environment in several days to several weeks. It can be said that there is a significant contrast with the fact that it is extremely difficult to place a stent in the body for a long period of time as described above because peeling can occur.
[0021]
In the present invention, the primer layer P is formed on the stent substrate 11 as described above, and the stent substrate 11 is coated with a water-absorbing polymer material that absorbs at least 100% of its own weight of water. After forming the drug holding layer M on the base material 11, the stent base material 11 is immersed in an aqueous solution of the bioactive agent for a predetermined time, and then dried to introduce the bioactive agent into the drug holding layer M. it can. Further, the stent 1 having a four-layer structure including the stent base material 11 can be obtained by forming the coating layer 12 by coating the drug holding layer M of the stent base material 11 with a polymer material.
Therefore, it is possible to obtain the stent 1 in which the bioactive agent is not bonded to the polymer material in the drug holding layer M, that is, contains the bioactive agent in a state of being physically mixed and dispersed. As described above, the thickness of the drug holding layer M and the coating layer 12 formed on the stent base material 11 can be arbitrarily determined according to the concentration of the physiologically active drug to be contained, the desired elution amount, the change over time in the elution amount, and the like. Although it can be adopted, it is usually 0.1 to 200 μm, preferably 0.1 to 50 μm.
[0022]
Here, the physiologically active agent defined in the present invention includes, for example, an anticancer agent such as paclitaxel, a gene therapeutic agent such as HGF (hepatocyte growth factor), an antiplatelet agent such as ticlopidine hydrochloride, other antibiotics, and an immunosuppressant. There is no particular limitation as long as it is water-soluble, such as a statin drug, can be introduced into the drug holding layer M, and is gradually released from the coating layer 12 by diffusion or other mechanism in a living body. These known bioactive agents can be used, and may be other than these.
[0023]
Hereinafter, embodiments of the stent of the present invention will be described with reference to the drawings.
FIG. 1 is a schematic diagram showing an example of the stent of the present invention, as described above. The stent 1 is composed of a stainless steel stent base material 11 as shown in a sectional view of FIG. The outer peripheral surface is sequentially covered with a primer layer P, a medicine holding layer M, and a coating layer 12. In the case of this stent 1, the surface of the stent substrate 11 is first treated with a primer having an affinity for both the metal constituting the stent substrate 11 and the water-absorbing polymer material constituting the drug holding layer M. After the primer layer P is formed, the drug holding layer M is formed by coating with a water-absorbing polymer material, and after introducing a bioactive agent into the drug holding layer 4, the drug holding layer 4 is coated with the polymer material. This is an example of a stent 1 having a four-layer structure including a stent base material 11 by forming a coating layer 12 by covering with a stent.
[0024]
As described above, in the method of forming the coating layer 12 and the drug holding layer M, the coating layer (coating layer 12 and drug holding layer M) can be formed by applying the coating solution by spraying or dipping. Here, the number of times of spraying or dipping may be one, but the thickness of the coating layer (coating layer 12, drug holding layer M) is adjusted according to the concentration of the polymer material forming the coating layer 12 and drug holding layer M. In order to do so, a method of applying in a plurality of times is usually used.
[0025]
【Example】
Hereinafter, the present invention will be described with reference to examples, but the present invention is not construed as being limited to these examples.
[0026]
[Comparative Example 1] (Stability test 1 of polymer material applied to stent in water environment)
(1) Tecophilic HP-93A-100 (polyether-type thermoplastic polyurethane, solution (1)) and Carbothane PC-3585A (polycarbonate-type thermoplastic polyurethane, solution (2)) which are water-absorbing polymers 2.0 g) was dissolved in 100 ml of tetrahydrofuran (THF) to prepare a 2% by mass solution (solutions (1) and (2)).
(2) The solution (1) is applied to the tubular stent 1 (stent base material 11) having the pattern shown in FIG. 1 and dried to cover the drug holding layer M, and then the stent 1 is treated with a 10% sodium heparin aqueous solution. After immersion for 1 hour, vacuum drying was performed to introduce a bioactive agent (heparin). Thereafter, the solution (2) was applied to form a coating layer 12 to obtain a stent sample. The film thickness was about 20 μm, and the amount of the bioactive agent introduced was about 200 μg.
[0027]
(3) After the stent sample was expanded, it was placed in a test tube containing 3 ml of a pH 7.4-phosphate buffer, and sampled with time at 37 ° C. while shaking at a rate of 60 times / min. Then, the sustained release of the physiologically active agent and the surface of the stent were visually observed and observed with a microscope, and the presence or absence of peeling of the coating film (drug holding layer M, coating layer 12) was observed.
As a result, it was found that the coating film (the drug holding layer M and the coating layer 12) peeled off in about 2 weeks in an aqueous solution environment. Sustained release of the bioactive agent could be confirmed up to 2 weeks when peeling occurred.
[0028]
[Example 1] (Stability test 2 in a water environment of a polymer material applied to a stent)
(1) 1.0 g of an epoxy silane coupling agent (KBM403 (3-glycidoxypropyltrimethoxysilane): manufactured by Shin-Etsu Chemical Co., Ltd.) is dissolved in 100 ml of MeOH / water (50/50), and a 1% by mass solution is dissolved. Was adjusted.
(2) Tecophilic HP-93A-100 (polyether-type thermoplastic polyurethane, solution (1)) and Carbothane PC-3585A (polycarbonate-type thermoplastic polyurethane, solution (2)), which are water-absorbing polymers. 2.0 g) was dissolved in 100 ml of tetrahydrofuran (THF) to prepare a 2% by mass solution (solutions (1) and (2)).
[0029]
(3) First, the solution of (1) is applied to the tubular stent 1 (stent base material 11) having the pattern shown in FIG. 1, the methanol / water is volatilized, and a pretreatment with a silane coupling agent is performed. Layer P was formed. Next, in the same manner as in Comparative Example 1, formation of the drug holding layer M, introduction of the physiologically active drug, and formation of the coating layer 12 were performed to obtain a stent sample. The film thickness was about 20 μm, and the amount of the bioactive agent introduced was about 210 μg.
(4) After the stent sample was expanded, it was placed in a test tube containing 3 ml of a pH 7.4-phosphate buffer, and sampled with time at 37 ° C. while shaking at a rate of 60 times / min. The surface of the stent was visually observed and observed with a microscope to observe the sustained release of the drug and the peeling of the coating film (the drug holding layer M and the coating layer 12).
As a result of Example 1, it was confirmed that the coating film (drug holding layer M, coating layer 12) was stably present for about two months or more in an aqueous solution environment. In addition, the release of the bioactive agent was confirmed even in the second month, though it was a trace amount.
[0030]
[Comparative Example 2] (As a comparative example, a sustained release test using a polymer material having low water absorption)
(1) 1.0 g of an epoxy silane coupling agent (KBM403 (3-glycidoxypropyltrimethoxysilane): manufactured by Shin-Etsu Chemical Co., Ltd.) is dissolved in 100 ml of methanol / water (50/50), and a 1% by mass solution is dissolved. Was adjusted.
(2) 2.0 g each of Pellecene 2363-80AE (polyether type thermoplastic polyurethane, solution (1)) and Carbothane PC-3585A (polycarbonate type thermoplastic polyurethane, solution (2)) in 100 ml of THF To prepare a 2% by mass solution.
[0031]
(3) After forming the pattern shown in FIG. 1 and treating it with an epoxy-based silane coupling agent to form a primer layer P in the same manner as in Example 1, forming a drug holding layer M, introducing a bioactive drug, The coating layer 12 was formed to obtain a stent sample. The film thickness was about 20 μm, and the amount of drug introduced was about 200 μg.
Similarly, after the stent sample was expanded, it was placed in a test tube containing 1 ml of a pH 7.4-phosphate buffer and shaken at 37 ° C. for evaluation.
As a result, it was confirmed that the coating film (drug holding layer M, coating layer 12) of the sample of Comparative Example 2 was stably present for about two months or more in an aqueous solution environment, but the amount of sustained release was very small, and It was below the detection limit in the eyes.
[0032]
As described above, from the results of Comparative Examples 1 and 2 and Example 1, in the stent of the present invention, the coating film (drug-retaining layer M and coating layer 12) basically remained for a long period (60 days). It was confirmed that there was no peeling from the stent substrate 11. Actually, the release behavior of the bioactive agent from the stent 1 coated with a water-absorbing polymer material containing a bioactive agent (antithrombotic agent) such as sodium heparin is not limited to about 30 days. In addition, it was confirmed that the drug holding layer M and the coating layer 12 were not peeled off from the stent base material 11 over a long period of about 60 days, and that the release rate of the bioactive agent could be controlled. .
[0033]
In the embodiment, sodium heparin is used as an example of the bioactive agent, but it is water-soluble and can be introduced into the drug holding layer M, and is gradually released from the coating layer 12 by diffusion or other mechanism in a living body. If it is a thing, it is not limited to this in particular.
[0034]
【The invention's effect】
According to the present invention, a drug holding layer M made of a water-absorbing polymer is formed, a physiologically active drug is contained and held in the drug holding layer M, and the outermost surface is formed of a polymer material having high stability in a living body. By doing so, it is possible to provide a stent having a sustained release of a bioactive agent that is stable over a long period of time and stability in the body.
Further, according to the stent of the present invention, the sustained release amount and rate of the bioactive agent can be controlled by appropriately changing the content of the agent and the thickness of the agent holding layer M and the coating layer 12.
[Brief description of the drawings]
1 is a schematic view of a stent of the present invention; FIG. 2 is a partially enlarged cross-sectional view of the stent of FIG. 1;
1 Stent 11 base material (stent base material)
12 Coating layer M Drug holding layer P Primer layer

Claims (8)

A stent (1) characterized in that the surface of a stent substrate (11) is coated in the order of primer layer (P) / drug holding layer (M) / coating layer (12). The drug holding layer (M) is made of a water-absorbing polymer material that contains a bioactive agent, releases the bioactive agent in vivo, and absorbs at least 100% of its own weight of water,
The primer layer (P) is made of a material having a high affinity for both the stent base material (11) and the water-absorbing polymer material constituting the drug holding layer (M),
The stent (1), wherein the covering layer (12) is made of a polymer material capable of covering the drug holding layer (M). The stent (1) according to claim 1 or 2, wherein the water-absorbing polymer material constituting the drug holding layer (M) is a polyether-based polyurethane. The stent (1) according to any one of claims 1 to 3, wherein the polymer material covering the drug holding layer (M) is a polycarbonate-based polyurethane. The stent (1) according to any one of claims 1 to 4, wherein the primer layer (P) is a silane coupling agent having a hydrolyzable group and an organic functional group. The stent (1) according to any one of claims 1 to 5, wherein the primer layer (P) is a cyanoacrylate adhesive. A method for producing a stent (1), comprising the following steps:
(1) a step of coating the surface of the stent substrate (11) with a primer layer (P);
(2) a step of coating the surface of the primer layer (P) with a drug holding layer (M);
(3) a step of coating the surface of the drug holding layer (M) with a coating layer (12); A solution in which a water-absorbing polymer material is dissolved is applied or immersed on the surface of the stent substrate (11) coated with the primer layer (P), and the solvent is volatilized to form a drug holding layer (M). 8. The bioactive agent is introduced into the drug holding layer (M) by immersing the stent substrate (11) in an aqueous solution of the bioactive agent for a predetermined time and then drying the stent base material (11). A method for producing a stent (1).

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