JP2012196264A - Stent and production method thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an extensible stent having both of superior tensile strength and ductility.SOLUTION: This extensible stent includes a stent body 1, at least a part of the stent body 1 is composed of tungsten alloy, and the crystal grain size of the part composed of the tungsten alloy is 5 μm or less.

Description

  The present invention relates to an expandable stent used for treatment of a lumen in a living body and a manufacturing method thereof.

  A stent is a medical device that is installed in a lesion in a living body lumen such as a blood vessel, lymphatic vessel, bile duct, ureter, etc., and maintains the diameter of the tube appropriately to ensure the passage of each lumen. is there.

  For the material constituting the stent, two contradictory mechanical properties of high tensile strength and high ductility are required at the same time. If the tensile strength is low, the radial force (radial strength) required for the stent cannot be obtained, and if the ductility is low, the stent will break when it is placed and expanded. Because it ends up.

An alloy may be used as a material constituting the stent, but a trade-off relationship is recognized between the tensile strength and ductility of the alloy. That is, the alloy generally has a low ductility when the strength is increased, and the strength is decreased when the ductility is improved.
Among such alloys, conventionally, for example, stainless steel 316L, cobalt alloy L605, cobalt alloy MP32N, and the like are used for the balloon expandable stent, and these have a tensile strength of 300 MPa and a ductility of 40%.

In recent years, the demand for mechanical properties for materials constituting the stent has been increasing, and higher physical properties than the conventional mechanical properties have been demanded.
In particular, when a metal material such as an alloy having a high tensile strength is used as a constituent material of the stent, the thickness of the stent can be reduced, and the dose of metal into the living body can be reduced. Has been.

Among high-strength metal materials that have been put into practical use, tungsten alloys mainly composed of tungsten have high tensile strength.
For example, Patent Document 1 discloses a medical implant such as a stent composed of “an alloy containing tungsten and rhenium” in which tungsten is “amount in the range of 75 wt% to 99 wt%” ( [Refer to [Claim 1], [Claim 2], etc.).

Japanese Patent No. 4516757

As tungsten alloys, varieties (manufactured by PLANSE) such as WVM, WC, WL, WT, WRe, WCu, DENSIMET, and INERMET have been put to practical use. Among them, WRe (tungsten-rhenium alloy) has tensile strength and ductility. It is considered as a balanced alloy.
However, although the tensile strength is 1000 MPa or more, the ductility is 20% or less, and thus the above-described requirements for the ductility are not satisfied.
Further, Patent Document 1 does not disclose tensile strength and ductility, and it is unclear whether these physical properties satisfy the above-described requirements.

  The present invention has been made in view of the above points, and provides an expandable stent which is a stent in which at least a part of a stent body is made of a tungsten alloy and has both excellent tensile strength and ductility. For the purpose.

As a result of diligent studies to achieve the above object, the present inventors have found that by reducing the crystal grains of the tungsten alloy portion, the ductility can be improved without impairing the tensile strength, and the present invention has been completed. I let you.
That is, the present invention provides the following (1) to (13).

  (1) An expandable stent comprising a stent body, wherein at least a part of the stent body is made of a tungsten alloy, and the crystal grain size of the portion made of the tungsten alloy is 5 μm or less.

  (2) The expandable stent according to (1), wherein the entire stent body is made of the tungsten alloy.

  (3) The expandable stent according to (1) or (2), wherein the tungsten alloy is a tungsten-rhenium alloy (W-Re alloy).

  (4) The surface of the stent body is provided with a layer formed using a composition containing a biological physiologically active substance and a biodegradable polymer, according to any one of (1) to (3) above. Expandable stent.

  (5) The surface of the stent body is provided with a layer containing a biological physiologically active substance and a layer containing a biodegradable polymer in this order, according to any one of (1) to (3). Expandable stent.

  (6) The biological physiologically active substance is an anticancer agent, immunosuppressant, antibiotic, antirheumatic agent, antithrombotic agent, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist, antihyperlipidemia Drugs, integrin inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, anti-inflammatory drugs, biological materials, The expandable stent according to (4) or (5) above, which is at least one selected from the group consisting of an interferon and a NO production promoting substance.

  (7) The biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polylactic acid, polycaprolactone, polyhydroxybutyric acid, cellulose, polyhydroxybutyrate valeric acid, and polyorthoester, or The expandable stent according to (4) or (5) above, which is a copolymer, a mixture, or a composite thereof.

  (8) The expandable stent according to any one of (1) to (7), wherein the stent body is a tubular body.

  (9) The expandable stent according to any one of (1) to (8), which is a balloon expandable stent.

  (10) The expandable stent according to any one of (1) to (8), which is a self-expanding stent.

  (11) A step of preparing a metal material at least partly composed of a tungsten alloy, and a crystal grain size of the portion composed of the tungsten alloy is reduced to 5 μm or less by subjecting the metal material to a refinement process. A step of forming a stent body from the metal material that has been subjected to the micronization treatment, and obtaining an expandable stent according to any one of (1) to (10). A method for manufacturing a stent.

  (12) The expandable stent manufacturing method according to (11), wherein the miniaturization process is a high strain processing process.

  (13) The method for producing an expandable stent according to (12), wherein the high strain processing is ECAE processing.

  According to the present invention, an expandable stent having excellent tensile strength and ductility can be provided.

It is a side view which shows the one aspect | mode of the stent of this invention. FIG. 2 is an enlarged cross-sectional view taken along line AA in FIG. 1.

[Stent]
An expandable stent of the present invention (hereinafter, also simply referred to as “the stent of the present invention”) includes a stent body, and at least a part of the stent body is made of a tungsten alloy. An expandable stent having a crystal grain size of 5 μm or less.

[Stent body]
The stent body is preferably a tubular body because it can be stably placed in a lumen in a living body such as a blood vessel.
The stent main body which is a tubular body includes a substantially cylindrical one having an inner surface and an outer surface. Specifically, for example, a stent in which an opening is provided in a substantially cylindrical pipe made of a tungsten alloy described later. A main body, a stent main body formed by braiding wires and fibers into a cylindrical shape, and the like are included.
The length and thickness of the stent body vary depending on the application, but usually the length is 5 to 500 mm, and the thickness (diameter of a substantially circular cross section) is 1 to 50 mm.

  Next, an example of the stent body (stent 1) will be described with reference to FIGS. However, the present invention is not limited to this.

FIG. 1 is a side view showing an embodiment of the stent of the present invention, and FIG. 2 is an enlarged cross-sectional view taken along line AA of FIG.
As shown in FIG. 1, the stent 1 is an elongated cylindrical body extending in one direction (major axis direction) with both ends opened. On the side surface of the cylindrical body, a large number of openings are formed to communicate the outer peripheral side and the inner peripheral side.

The stent 1 is formed of a linear member 2 and has a substantially rhombic element 11 having an opening inside as a basic unit. A plurality of elements 11 are continuously arranged in the circumferential direction of the stent 1 and joined together to form an annular unit 12. The annular unit 12 is connected to an adjacent annular unit via a linear connecting member 13. Thus, the plurality of annular units 12 are continuously arranged in the longitudinal direction of the stent 1 in a state where the plurality of annular units 12 are partially coupled.
As shown in FIG. 2, the cross-sectional shape of each linear member 2 is such that the outer surface 31 forms an arc that is slightly longer than the inner surface 32. The stent 1 can be expanded and contracted in the radial direction of the cylindrical body by deforming each linear member 2.

In the present invention, at least a part of such a stent body is made of a tungsten alloy, and the entire stent body is made of a tungsten alloy because both the tensile strength and ductility of the entire stent are excellent. Is preferred.
Next, the tungsten alloy constituting the stent body will be described.

[Tungsten alloy]
Tungsten alloy is a general term for alloys containing tungsten (W) as a main component. Here, the “main component” means that the amount of tungsten in the tungsten alloy is, for example, 50% by mass or more.

  The tungsten alloy used in the present invention is not particularly limited as long as it has high safety in vivo and can obtain the above crystal grain size.

  Examples of elements other than tungsten contained in the tungsten alloy include rhenium (Re), hafnium (Hf), thorium (Th), carbon (C), tantalum (Ta), zirconium (Zr), yttrium (Y), Nickel (Ni), titanium (Ti), neodymium (Nd), niobium (Nb), zinc (Zn), potassium (K), calcium (Ca), aluminum (Al), lithium (Li), scandium (Sc), Biocompatible elements such as manganese (Mn), copper (Cu), iron (Fe); lanthanum (La), cerium (Ce), praseodymium (Pr), samarium (Sm), europium (Eu), gadolinium (Gd) Terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), yt Rubiumu (Yb), rare earth elements such as lutetium (Lu); and the like.

Examples of the tungsten alloy containing these elements include WVM, WC, WL, WT, WRe, WCu, DENSIMET, INERMET, etc., among them because of the excellent balance between tensile strength and ductility. WRe (W-Re alloy, tungsten-rhenium alloy) is preferable.
As the W-Re alloy, those having high ductility are preferable, and examples thereof include W-Re26 (Re: 26% by mass).

[Parts made of tungsten alloy]
In the present invention, the crystal grain size of a portion made of a tungsten alloy (hereinafter also referred to as “tungsten alloy portion”) in the stent body is 5 μm or less. In this way, by making the crystal grains of the tungsten alloy portion fine and making the crystal grain size 5 μm or less, the ductility is improved without impairing the tensile strength. Thus, the tensile strength and ductility of the stent body are improved, and physical properties necessary for the stent can be obtained.
At this time, the crystal grain size of the tungsten alloy portion is preferably 1 μm or less because the tensile strength and ductility of the stent body become better.

  Further, the crystal grain size of the tungsten alloy part is preferably 0.01 μm or more, and more preferably 0.1 μm or more.

  In the present invention, the “crystal grain size” means an average crystal grain size measured by a linear intercept method from a structural photograph obtained by observation using a transmission electron microscope, a scanning electron microscope, or an optical microscope. Say.

  The treatment for making the crystal grains of the tungsten alloy portion finer and making the crystal grain size 5 μm or less (hereinafter referred to as “refining treatment”) is not particularly limited, and includes, for example, high strain processing.

The high strain processing is processing for refining crystal grains by repeatedly applying plastic strain without deforming the shape of a metal material. The refinement of crystal grains by high strain processing is not particularly limited in the composition of the alloy, and can be applied to an alloy having a preferable composition from the viewpoint of biocompatibility and decomposition rate. Note that annealing may be performed after the high strain processing.
Specifically, as such strong strain processing, for example, rolling processing, hot drawing processing, ECAE processing, and the like can be suitably used.

The ECAE (Equal Channel Angular Extrusion) process is a process in which dynamic recrystallization is generated in the alloy by applying an extremely large shear strain to the tungsten alloy in a bent die to refine crystal grains. In addition, you may heat in the case of a process.
ECAE treatment is preferable because the crystal grain size of the tungsten alloy portion is easily reduced. According to the ECAE treatment, the crystal grain size can be 5 μm or less, and in some cases 1 μm or less.

[Stent body surface layer]
The stent of the present invention includes a layer (hereinafter, also referred to as “composition layer”) formed using a composition containing a biological physiologically active substance and a biodegradable polymer on the surface of the stent body. May be. When the stent of the present invention provided with the composition layer is placed on a lesion in a lumen in a living body, the biological physiologically active substance is gradually released to promote treatment of the lesion.

The mass ratio of the biologically physiologically active substance to the biodegradable polymer in this composition (biologically physiologically active substance / biodegradable polymer) is preferably 1/99 to 99/1, and 30/70 More preferably, it is -70/30. This is because it is possible to mount an amount of biological and physiologically active substance necessary for the treatment of a lesioned part while considering the physical properties and degradability of the biodegradable polymer.
The thickness of the composition layer is preferably from 0.1 to 100 μm, more preferably from 1 to 15 μm, still more preferably from 3 to 7 μm. A layer having a thickness within this range can be easily inserted into a lumen in a living body such as a blood vessel.

When forming a composition layer on the surface of the stent body, for example, it is performed as follows.
First, the biological physiologically active substance and the biodegradable polymer are mixed in a solvent such as acetone, ethanol, chloroform, tetrahydrofuran or the like so that the concentration is 0.001 to 20% by mass, preferably 0.01 to 10% by mass. And dissolve to obtain a solution. Next, the obtained solution is applied to the surface of the stent body using a spray, a dispenser or the like, and then the solvent is volatilized to form a composition layer on the surface of the stent body.

  In the stent of the present invention, the surface of the stent body includes a layer containing a biological physiologically active substance (hereinafter also referred to as “biological physiologically active substance layer”) and a layer containing a biodegradable polymer ( (Hereinafter also referred to as “biodegradable polymer layer”) in this order. Thereby, stabilization of the biological physiologically active substance and stepwise release of the biologically physiologically active substance to the lesioned part are possible.

The thickness of the biological physiologically active substance layer is preferably 0.1 to 100 μm, more preferably 1 to 15 μm, and further preferably 3 to 7 μm.
The thickness of the biodegradable polymer layer is preferably 0.1 to 100 μm, more preferably 1 to 15 μm, and further preferably 3 to 7 μm.
A layer having a thickness within this range can be easily inserted into a lumen in a living body such as a blood vessel, and is necessary for treatment of a lesioned part while taking into consideration the physical properties and degradability of a biodegradable polymer. An amount of biologically bioactive substance can be mounted.
The surface of the stent body may include a plurality of biological and physiologically active substance layers and biodegradable polymer layers.

In the case of forming a biological physiologically active substance layer and a biodegradable polymer layer on the surface of the stent body, for example, the following is performed.
First, a biological physiologically active substance is dissolved in a solvent to a predetermined concentration to obtain a solution, and the obtained solution is applied to the surface of the stent body using a spray, a dispenser, etc. By volatilizing the solvent, a biological physiologically active substance layer is formed on the surface of the stent body.
Next, similarly for the biodegradable polymer, a solution is obtained by dissolving in a solvent so as to have a predetermined concentration, and the obtained solution is applied on the biological physiologically active substance layer, and then the solvent is volatilized. By doing so, a biodegradable polymer layer is formed.
In this case, acetone, ethanol, chloroform, tetrahydrofuran or the like can be used as the solvent in any case, and the concentration is, for example, 0.001 to 20% by mass, preferably 0.01 to 10% by mass. is there.

  The biologically and physiologically active substance is not particularly limited as long as it suppresses luminal restenosis and reocclusion that may occur when the stent of the present invention is placed in a lesion, and can be arbitrarily selected. Anticancer agent, immunosuppressive agent, antibiotic, anti-rheumatic agent, antithrombotic agent, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist, antihyperlipidemic agent, integrin inhibitor, antiallergic agent, Antioxidant, GPIIbIIIa antagonist, retinoid, flavonoid, carotenoid, lipid improver, DNA synthesis inhibitor, tyrosine kinase inhibitor, antiplatelet drug, anti-inflammatory drug, bio-derived material, interferon, and NO production promoter At least one selected from the group is preferable because the lesion can be treated by controlling the behavior of cells in the lesion tissue.

  As the anticancer agent, for example, vincristine, vinblastine, vindesine, irinotecan, pirarubicin, paclitaxel, docetaxel, methotrexate and the like are preferable.

  As an immunosuppressant, for example, sirolimus, tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, everolimus, ABT-578, AP23573, CCI-779, gusperimus, mizoribine and the like are preferable.

As the antibiotic, for example, mitomycin, adriamycin, doxorubicin, actinomycin, daunorubicin, idarubicin, pirarubicin, aclarubicin, epirubicin, pepromycin, dinostatin styramer and the like are preferable.
As the anti-rheumatic agent, for example, methotrexate, sodium thiomalate, penicillamine, lobenzalit and the like are preferable.
As the antithrombotic drug, for example, heparin, aspirin, antithrombin preparation, ticlopidine, hirudin and the like are preferable.

As the HMG-CoA reductase inhibitor, for example, cerivastatin, cerivastatin sodium, atorvastatin, rosuvastatin, pitavastatin, fluvastatin, fluvastatin sodium, simvastatin, lovastatin, pravastatin and the like are preferable.
As the ACE inhibitor, for example, quinapril, perindopril erbumine, trandolapril, cilazapril, temocapril, delapril, enalapril maleate, lisinopril, captopril and the like are preferable.
As the calcium antagonist, for example, hifedipine, nilvadipine, diltiazem, benidipine, nisoldipine and the like are preferable.

As the antihyperlipidemic agent, for example, probucol is preferable.
As the integrin inhibitor, for example, AJM300 is preferable.
As the antiallergic agent, for example, tranilast is preferable.
As the antioxidant, for example, α-tocopherol is preferable.
As the GPIIbIIIa antagonist, for example, abciximab is preferable.
As the retinoid, for example, all-trans retinoic acid is preferable.

As the flavonoid, for example, epigallocatechin, anthocyanin, proanthocyanidin and the like are preferable.
As the carotenoid, for example, β-carotene, lycopene and the like are preferable.
As the lipid improving agent, for example, eicosapentaenoic acid is preferable.
As the DNA synthesis inhibitor, for example, 5-FU is preferable.
As the tyrosine kinase inhibitor, for example, genistein, tyrphostin, arbustatin, staurosporine and the like are preferable.

As the antiplatelet drug, for example, ticlopidine, cilostazol, clopidogrel and the like are preferable.
As the anti-inflammatory agent, for example, steroids such as dexamethasone and prednisolone are preferable.
Examples of the bio-derived material include EGF (epidemal growth factor), VEGF (basic endowment growth factor), HGF (hepatocyte growth factor), PDGF (platelet growth factor), and PDGF (platelet growth factor).

As interferon, for example, interferon-γ1a is preferable.
As the NO production promoting substance, for example, L-arginine is preferable.

  These biological and physiologically active substances may be used alone or in combination of two or more according to the case.

  The biodegradable polymer is not particularly limited as long as it is a polymer that gradually biodegrades when the stent of the present invention is placed in a lesion, and does not adversely affect the living body. At least one selected from the group consisting of polylactic acid, polycaprolactone, polyhydroxybutyric acid, cellulose, polyhydroxybutyrate valeric acid, and polyorthoester, or a copolymer, mixture, or composite thereof. Preferably there is. This is because the reactivity with the living tissue is low and the decomposition rate in the living body can be controlled.

[Stent manufacturing method]
The stent production method for obtaining the stent of the present invention (hereinafter also referred to as “the stent production method of the present invention”) is not particularly limited as long as it is a method capable of obtaining the stent of the present invention, but at least a part thereof Preparing a metal material composed of tungsten alloy, subjecting the metal material to a refinement treatment to reduce the crystal grain size of the portion composed of the tungsten alloy to 5 μm or less, and the refinement And a step of forming a stent body from the treated metal material.

In this case, first, an ingot of a tungsten alloy (for example, W-Re26) is prepared, and the ingot is refined.
As described above, as the miniaturization process, a strong strain processing process is exemplified, and as the strong strain process, a rolling process, an ECAE process, or the like is preferably used.
Next, the ingot that has been subjected to the fine processing is polished to produce a pipe having a desired size, and an opening is formed on the surface of the pipe. In addition, after producing a pipe, you may perform a hot drawing process and refine | miniaturize a crystal grain further. As a method for forming the opening, for example, an opening pattern is attached to the pipe, and the pipe other than the opening pattern is melted by an etching technique such as laser etching or chemical etching to form the opening; And a method of forming an opening by cutting a pipe according to a pattern by a laser cutting technique based on the pattern information. Thereby, the stent of this invention whose stent main body is a tubular body is manufactured.

[How to use the stent]
The method of using the stent of the present invention is the same as the method of using a normal stent, and is not particularly limited. For example, the stent of the present invention may be used in a blood vessel for the purpose of expanding a coronary artery narrowed by arteriosclerosis to improve blood flow.
In this case, the stent of the present invention can be used as a balloon expandable stent or a self-expandable stent.
In the former case, the stent of the present invention itself does not have an expansion function, and after being inserted into the lesioned part, it is expanded (plastically deformed) by the expansion force of the balloon and is tightly fixed to the inner wall of a lumen such as a blood vessel.
In the latter case, the stent of the present invention is compressed in the direction of the central axis when inserted into a lumen in a living body, opened and expanded at a lesioned portion, and restored to a shape before compression, whereby a lumen such as a blood vessel is obtained. Closely fixed to the inner wall.

  Hereinafter, the present invention will be specifically described with reference to examples. However, the present invention is not limited to these.

<Experimental example 1>
First, an ingot of W-Re26 was prepared, and this ingot was subjected to solution treatment under the conditions of 700 K and 36000 seconds using an electric furnace to obtain a test piece 1.
Further, the test piece 1 was subjected to ECAE treatment at 573 K (reduction rate per pass: about 5%, final reduction rate: 50%), and then annealed at 473 K for 50000 seconds to obtain a test piece 2.

About the test piece 1 and the test piece 2, it observed with the magnification of 100-1000 times using the optical microscope (made by Leica), and from the obtained structure | tissue photograph, crystal grain size (average crystal grain size) was carried out by the linear intercept method. ) Was measured.
As a result, the crystal grain size of the test piece 1 was 80 to 120 μm, whereas the crystal grain size of the test piece 2 was 1 to 4 μm. That is, in the test piece 2, the crystal grains could be made finer than in the test piece 1.

  Next, a square bar material having a thickness of 8 mm, a width of 8 mm, and a length of 100 mm was cut out from the test piece 2 and subjected to centerless polishing to be processed into a round bar material having a diameter of 3 mm. A through hole having a cross-sectional diameter of 2.4 mm was formed in a hollow round bar by lathe processing to produce a pipe. This pipe was hot drawn at 573 K to obtain a pipe having an outer diameter of 2 mm and an inner diameter of 1.6 mm (hereinafter referred to as “test piece 3”).

  As a result of measuring the crystal grain size of the test piece 3 in the same manner as described above, the crystal grain size was 0.2 to 0.9 μm. That is, in the test piece 3, the crystal grains could be further refined than in the test piece 2. This is thought to be due to dynamic recrystallization during the hot drawing process.

  Next, a test piece having a thickness of 0.4 mm, a width of 3 mm, and a length of 5 mm (referred to as test piece 10, test piece 20, and test piece 30, respectively) is rolled from test piece 1, test piece 2, and test piece 3. Cut parallel to the direction, a tensile test was performed at room temperature, and tensile strength [MPa] and ductility [%] were measured. The measurement results are shown in Table 1 below.

  From the results shown in Table 1, it was found that the ductility can be greatly improved while maintaining the tensile strength by making the crystal grains finer.

<Experimental example 2>
The pipe (test piece 3) obtained in Experimental Example 1 was laser processed to produce a stent having a diameter of 2 mm and a length of 15 mm. When this stent was expanded to a diameter of 3 mm using a balloon catheter, no damaged portion was confirmed. Thereby, it turned out that a practical stent can be produced.

<Experimental example 3>
First, a mass ratio of a biological physiologically active substance (sirolimus which is an immunosuppressive agent), a biodegradable polymer (polylactic acid, weight average molecular weight: 75,000), and a plasticizer (acetylated monoglyceride) is 5 : A solution was obtained by dissolving in acetone as a solvent at a ratio of 4: 1 so that the concentration was 0.5% by mass.
The obtained solution is sprayed onto the surface of the same stent (stent body) as that prepared in Experimental Example 2 using a spray, and the solvent is completely volatilized using a vacuum dryer, and the mass is about 0.6 mg. A layer (composition layer) having an average thickness of 10 μm was formed on the outer surface of the stent body.
When this stent was expanded to a diameter of 3 mm using a balloon catheter in the same manner as in Experimental Example 2, no damaged portion was confirmed. In addition, it was confirmed that a practical stent could be produced with respect to the composition layer without cracking or falling off.

1 Stent (Stent body)
DESCRIPTION OF SYMBOLS 11 Element of substantially rhombus 12 Ring unit 13 Connecting member 2 Linear member 31 Outer surface 32 Inner surface

Claims (13)

Comprising a stent body,
At least a portion of the stent body is made of a tungsten alloy;
An expandable stent, wherein the portion made of the tungsten alloy has a crystal grain size of 5 µm or less.   The expandable stent according to claim 1, wherein the entire stent body is composed of the tungsten alloy.   The expandable stent according to claim 1 or 2, wherein the tungsten alloy is a tungsten-rhenium alloy (W-Re alloy).   The expandable stent according to any one of claims 1 to 3, comprising a layer formed on a surface of the stent body using a composition containing a biological physiologically active substance and a biodegradable polymer.   The expandable stent according to any one of claims 1 to 3, comprising a layer containing a biological physiologically active substance and a layer containing a biodegradable polymer in this order on the surface of the stent body. The biological physiologically active substance is
Anticancer agent, immunosuppressive agent, antibiotic, antirheumatic agent, antithrombotic agent, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist, antihyperlipidemic agent, integrin inhibitor, antiallergic agent, antioxidant From the group consisting of agents, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, anti-inflammatory drugs, biological materials, interferons, and NO production promoters The expandable stent according to claim 4 or 5, which is at least one selected. The biodegradable polymer is
At least one selected from the group consisting of polyglycolic acid, polylactic acid, polycaprolactone, polyhydroxybutyric acid, cellulose, polyhydroxybutyrate valeric acid, and polyorthoesters, or a copolymer, a mixture thereof, or The expandable stent according to claim 4 or 5, which is a composite.   The expandable stent according to any one of claims 1 to 7, wherein the stent body is a tubular body.   The expandable stent according to any of claims 1 to 8, which is a balloon expandable stent.   The expandable stent according to any of claims 1 to 8, which is a self-expanding stent. Preparing a metal material at least partially composed of a tungsten alloy;
A step of reducing the crystal grain size of the portion made of the tungsten alloy to 5 μm or less by subjecting the metal material to a refinement treatment;
A method for producing an expandable stent, comprising: forming a stent body from the metal material that has been subjected to the miniaturization process, and obtaining the expandable stent according to any one of claims 1 to 10.   The method for producing an expandable stent according to claim 11, wherein the miniaturization process is a high strain processing process.   The method for producing an expandable stent according to claim 12, wherein the high strain processing is an ECAE process.