JP2007185365A - Stent and method of manufacturing stent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a stent capable of being stably carried and indwelt at a desired position of the lumen section of a tubular organ, and a method of manufacturing the stent. <P>SOLUTION: The stent 1 is used by being inserted and indwelt in the lumen section of the tubular organ of a living body, is provided with a mesh structure and is in a cylindrical shape as a whole, wherein a plurality of fine projections 11A1 are provided on at least a part of the area of the inner surface. Also, it is desirable that the fine projections 11A1 have the function of preventing slipping to the outer surface of a balloon when the stent 1 is inserted and indwelt in the lumen section. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a medical stent, and more particularly to a stent used by being inserted and placed in a tubular organ such as a blood vessel and a method for manufacturing the stent.

  2. Description of the Related Art Conventionally, a stent for inserting and placing in a lumen of a biological tubular organ (for example, a blood vessel, trachea, esophagus, bile duct, etc.) and supporting the tubular organ from the inside is known (for example, Patent Document 1). reference.).

  Such a stent usually has a plurality of linear unit struts, which are joined together to form a network structure, and has a cylindrical shape as a whole. For example, when such a stent is a balloon-expandable stent, it is held from the inner peripheral side of the stent by a balloon-attached catheter in a reduced diameter state, introduced into the lumen of the tubular organ, and the lumen is After being moved, the indwelling site is fixed (attached) by making the diameter expanded by expanding the balloon.

JP 2003-102847 A

  However, depending on the shape of the mesh structure, the stent according to Patent Document 1 slips with respect to the wall surface of the lumen when placed in the lumen, and is placed at a desired position in the lumen. There was a case that could not be done.

  Therefore, the present invention solves the above-described problems, and an object of the present invention is to provide a stent that can be stably transported and placed at a desired position in the lumen of a tubular organ, and a method for manufacturing the stent. There is.

In order to solve the above problems, the stent of the present invention is used by being inserted and placed in the lumen of a biological tubular organ, and has a plurality of openings and has a tubular shape as a whole,
It has a plurality of minute protrusions in at least a partial region of its inner surface. According to the present invention, when the stent is placed in the lumen while being held from the inner peripheral side by an instrument such as a catheter with a balloon, the inner surface of the stent with respect to the instrument is prevented from slipping by the microprotrusions, and the stent is It can be stably transported and placed at a desired position in the lumen of the tubular organ.

  In the present invention, each microprojection preferably has any one of a needle shape, a branch shape, and a scale shape. According to the present invention, the minute protrusions can be formed relatively easily by a plating method such as wet plating.

In the present invention, it is desirable that the fine protrusions exist in a range of 5000 or more and 200,000 or less per 1 mm ^{2 in the} region. According to the present invention, the stent can be stably transported and placed at a desired position in the lumen of the tubular organ while preventing damage to an instrument such as a balloon catheter.

  In the present invention, it is desirable that the average height of the microprojections is in the range of 5 μm to 50 μm. According to the present invention, the stent can be stably transported and placed at a desired position in the lumen of the tubular organ while preventing damage to instruments such as a balloon catheter and breakage of microprojections.

  In the present invention, it is desirable that the average width of the minute protrusions is in a range of 0.5 μm to 30 μm. According to the present invention, the stent can be stably transported and placed at a desired position in the lumen of the tubular organ while preventing damage to instruments such as a balloon catheter and breakage of microprojections.

  In the present invention, it is desirable that a filler is filled between the microprojections. According to the present invention, the filling material can be gradually released from the stent when the stent is in use.

  In the present invention, it is desirable that the filler contains a drug. According to the present invention, when the stent is in use, treatment can be performed by gradually releasing the drug from the stent.

  In the present invention, the drug is an antithrombotic agent, an antiplatelet agent, an immunosuppressive agent, a cell growth inhibitor, an anti-inflammatory agent, or an agent for promoting endothelial healing, or a combination of two or more. It is desirable to use it as a main component. According to the present invention, treatment can be performed by gradually releasing various drugs from the stent during use of the stent.

  In the present invention, the filler preferably contains a polymer having a function of holding the drug. According to this invention, by adjusting the kind and amount of the polymer, the release rate and the release amount of the filler from the stent can be made desired when the stent is in use.

  In the present invention, the polymer is preferably composed mainly of a bioabsorbable polymer. According to the present invention, when the stent is in use, the release rate and release amount of the filler from the stent can be made desirable, and the safety to the living body can be improved.

  In the present invention, the stent is preferably a balloon expandable stent. According to this invention, using a catheter with a balloon, the stent can be transported and placed at a desired position in the lumen while stably holding the stent.

  In the present invention, it is desirable that the microprotrusions have a function of preventing slipping with respect to the outer surface of the balloon when the stent is inserted and placed in the lumen. According to the present invention, slipping of the inner surface of the stent with respect to the balloon can be more reliably prevented when the stent is placed in the lumen while being held by the balloon catheter from the inner peripheral side.

  In the present invention, the stent is mainly composed of at least one selected from the group consisting of Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, and Ag, or an alloy containing at least one of them. It is desirable to be configured. According to the present invention, it can be suitably applied to a balloon-expandable stent, has excellent biocompatibility after placement, and can minimize degradation and degradation of characteristics in vivo. If noble metal is used as the constituent material of the stent, the X-ray contrast property can be improved.

  In the present invention, the stent is preferably composed of a Ni / Ti alloy as a main material. According to the present invention, it can be suitably applied to a self-expanding stent, has excellent compatibility with living tissue after placement, and can minimize deterioration and degradation of characteristics in vivo.

The stent manufacturing method of the present invention, the first step of preparing a cylindrical body,
A second step of forming a plurality of openings in the cylindrical body and forming a plurality of minute protrusions in at least a partial region of the inner surface of the cylindrical body. According to the present invention, a stent that can be stably transported and placed at a desired position in the lumen of a tubular organ is obtained.

  In the present invention, in the second step, it is preferable that the plurality of minute protrusions are formed by a wet plating method and / or a dry plating method. According to the present invention, the minute protrusions can be formed relatively easily.

  In the present invention, it is desirable that the surface of the cylindrical body is roughened prior to the second step. According to the present invention, the minute protrusions can be formed more easily.

  ADVANTAGE OF THE INVENTION According to this invention, it can convey and indwell stably to the desired position of the lumen | bore part of a tubular organ. A stent and a method for manufacturing the stent can be provided.

  Hereinafter, embodiments of a stent and a manufacturing method thereof according to the present invention will be described in detail with reference to the accompanying drawings.

First, the stent of the present invention will be described.
In FIG. 1, a stent 1 is used by being inserted and placed in a lumen of a living tubular organ, and the overall shape is substantially cylindrical.

  The stent 1 has a plurality of linear portions 11 and forms a network structure so that they are connected. An opening 10 is formed in a portion surrounded by a plurality of linear portions (struts) 11.

  Such a stent 1 is transported (conveyed) to a target site in the lumen of the tubular organ in a state where the outer diameter of the stent 1 is contracted (reduced diameter) (hereinafter referred to as a “reduced diameter state”). The Then, at this target site, the outer diameter of the stent 1 is expanded (expanded) by the restoring force of the stent 1 itself or by applying an external force so that the outer diameter of the stent 1 becomes larger than the outer diameter of the reduced diameter state. (Hereinafter referred to as “expanded diameter state”).

  The linear portions 11 are connected to each other at an intersection point 111 at an angle of less than 180 °, whereby each opening 10 has a rhombus shape by being surrounded by a polygonal shape (in this embodiment, four linear portions 11). Shape). With this configuration, the stent 1 has excellent radial flexibility while ensuring sufficient rigidity and strength. In addition, since sufficient rigidity and strength can be ensured, the stent 1 has excellent radiation supporting force.

  Here, in this specification, “radial flexibility” refers to flexibility in the direction of the arrow in FIG. 2A, that is, the direction from the central axis toward the outside. Further, “radiation support force” refers to a force that maintains the shape of the tubular organ in the expanded diameter state. Further, in this specification, “axial flexibility” means flexibility (easy to bend, that is, flexibility) in the direction of the arrow in FIG.

  As shown in FIG. 2 (a) and FIG. 2 (b), which is a partially enlarged view thereof, the linear portion 11 is substantially rectangular (rectangular).

The average cross-sectional area of the linear portion 11 varies slightly depending on the constituent material of the stent 1 is preferably in the range of 1 × 10 ^-5 mm ² or more 0.1 mm ² or less, 1 × 10 ^-4 mm ² or more A range of 0.01 mm ² or less is more desirable. If the cross-sectional area of the linear part 11 is too small (the linear part 11 is too thin), the rigidity of the stent 1 may be reduced, and the cross-sectional area of the linear part 11 is too large (the linear part 11 is too thick). ) And the axial flexibility (flexibility) of the stent 1 may decrease.

  Further, the cross-sectional shape of the linear portion 11 may be different in each portion of the stent 1, but it is desirable that the linear portion 11 is substantially constant over almost the entire stent 1 as shown in FIG. Thereby, it is possible to prevent the axial flexibility of the stent 1 from becoming uneven in each part.

  The cross-sectional shape of the linear portion 11 may be, for example, a polygon such as a circle, an ellipse, a square, a rhombus, a triangle, a pentagon, and a hexagon in addition to a quadrangle (rectangular shape) as shown in FIG.

  Although not shown, it is desirable that the edge of the stent 1 (linear portion 11) is rounded. Thereby, it is possible to prevent the inner wall of the tubular organ from being inadvertently damaged at the time of or after the placement of the stent 1. Further, when the stent 1 is applied to an intravascular stent, it is useful for preventing thrombus formation.

  2 (b), the linear portion 11 has an inner peripheral portion 11A located on the inner peripheral side of the stent 1 and an outer peripheral portion 11B located on the outer peripheral side of the stent 1. A plurality of minute protrusions 11A1 are formed on the surface of the inner peripheral portion 11A opposite to the outer peripheral portion 11B. That is, the stent 1 has a plurality of microprotrusions 11A1 on its inner surface. In the present embodiment, the plurality of minute protrusions 11A1 are formed only on the inner surface of the stent 1 and over the entire area thereof.

  When the stent 1 having such a microprotrusion 11A1 is transported and placed in the lumen while being held by an instrument such as a catheter with a balloon from its inner peripheral side, the slip of the inner surface of the stent 1 with respect to the instrument is minimal. The protrusion 11A1 can be prevented. As a result, the stent 1 can be stably transported and placed at a desired position in the lumen of the tubular organ.

  Therefore, it is desirable that the microprotrusions 11A1 have a function of preventing slipping with respect to the outer wall surface of a balloon such as a balloon-equipped catheter when the stent 1 is inserted and placed in the lumen. Since the microprotrusion 11A1 has such a function, the stent 1 can be stably transported and placed at a desired position in the lumen of the tubular organ.

  More specifically, the microprotrusion 11A1 may have any shape as long as it has the function described above, but it has any one of a needle shape, a branch shape, and a scale shape. It is desirable that Such a minute protrusion can be formed relatively easily by a plating method such as wet plating.

Further, it is desirable that the microprotrusions 11A1 exist in the range of 5000 to 200,000 per 1 mm ^{2 in the} area where the plurality of microprotrusions 11A1 are formed, and the range of 10,000 to 150,000 It is more desirable to exist in If the microprotrusion 11A1 exists in such a range, the stent 1 can be stably transported and placed at a desired position in the lumen of the tubular organ while preventing damage to instruments such as a balloon catheter. Can do.

  Further, the average height of the minute protrusions 11A1 is preferably in the range of 5 μm to 50 μm, and more preferably in the range of 10 μm to 30 μm. When the height of the microprotrusion 11A1 is formed in such a range, the stent 1 can be placed at a desired position in the lumen of the tubular organ while preventing damage to instruments such as a catheter with a balloon and damage to the microprotrusion 11A1. Can be transported and detained stably.

  In addition, the average width of the minute protrusions 11A1 is preferably in the range of 0.5 μm to 30 μm, and more preferably in the range of 1 μm to 20 μm. If the width of the microprotrusion 11A1 is formed in such a range, the stent 1 can be placed at a desired position in the lumen of the tubular organ while preventing damage to instruments such as a balloon catheter and damage to the microprotrusion 11A1. It can be stably transported and detained.

  In addition, the gap 11A2 between the microprotrusions 11A1 can be filled with a filler. In this case, when the stent 1 is in use, the release rate and the release amount of the filler from the stent 1 are adjusted (gradually). Giving release).

  As the filling material accommodated in the gap 11A2 between the microprotrusions 11A1, at least one of a drug, a cell, and a biological substance can be used.

  The drug accommodated in the gap 11A2 between the microprotrusions 11A1 is selected according to the type of tubular organ in which the stent 1 is placed, for example, an antithrombotic agent, an antiplatelet agent, an antiinflammatory agent, and an endothelial healing agent. Accelerators, analgesics / sedatives, antiproliferative agents (cell growth inhibitors), anticancer agents, immunosuppressants, and the like can be used.

  Such a drug is accommodated in the gap 11A2 between the microprotrusions 11A1, and is gradually released to the outside of the stent 1 during use to exhibit various therapeutic effects. In particular, when an agent having an anticancer agent as a main component is used as a drug, the anticancer agent can be selectively acted on the cancer tissue simply by placing the stent in the immediate vicinity of the cancer tissue when the stent 1 is in use. Therefore, while suppressing the usage amount of the anticancer agent to a small amount, the maximum anticancer effect is exhibited and the action of the anticancer agent on the whole body is prevented, and as a result, side effects due to the anticancer agent can be prevented. In addition, when an agent containing an immunosuppressive agent as a main component is used as a medicine, the immunosuppressive action can prevent inflammation at the indwelling site of the stent and prevent the living body from recognizing the stent as a foreign substance.

  Antithrombotic agents include, for example, heparin sodium, heparin calcium, low molecular weight heparin, heparin-like substance (low molecular dextran), hirudin, recombinant hirudin, argatroban, forskolin, bapiprost, prostaglandin E1, prostacyclin, prostacyclin family Body, aspirin, sulpyrine, dipyridamole, antithrombin III, streptokinase, urokinase, tissue plasminogen activator, prourokinase, etc. can be used.

  As the antiplatelet agent, for example, aspirin, ticlopidine, warfarin, dipyridamole and the like can be used.

As the anti-inflammatory agent, for example, dexamethasone, microsporine, etc. can be used.
As the endothelial healing promoter, for example, estradiol, tarafermin and the like can be used.

  As the analgesic / sedative, for example, pentazocine, buprenorphine hydrochloride, butorphanol tartrate, tramadol hydrochloride, opium alkaloid hydrochloride, morphine hydrochloride, pethidine hydrochloride, pethidine levalorphan, fentanyl citrate, fentanyl dropperidol and the like can be used.

  Examples of the antiproliferative agent (cell growth inhibitor) include somatostatin or its homologue, nitroprusside, colchicine, fish oil (ω3 fatty acid), steroidal agent, serotonin antagonist, calcium groove blocking antibody, hestamine antagonist, enzyme Inhibitors (eg, angiotensin converting enzyme inhibitors, prostaglandin synthase inhibitors, HMG-CoA reductase inhibitors, phosphodiesterase inhibitors, thiol protease inhibitors, methotrexate), growth factor antagonists (eg, fibroblast proliferation) Factor antagonists, platelet-derived growth factor antagonists), nitric oxide, and the like.

  Anticancer agents include, for example, nitrogen mustards such as mechlorethamine, nitrogen mustard N-oxide (nitromine), cyclophosphamide, melphalan, chlorambucil, triethylenethiophosphoramide, carbocon, triethylenemelamine, triethylene Ethyleneimines such as phosphoramide, alkyl sulfonic acids such as busulfan, nitrosoureas such as carmustine, lomustine, semustine and nimustine, triazenes such as dacarbazine, 8-azaguanine, 6-thioguanine, 6-mercaptopurine and 6-mercapto Purine anti-metabolites such as riboside, 6-chloropurine, azathioprine, 5-fluorouracil, 5-fluorodeoxyuracil, tegafur, cytarabine, ancitabine, azau Pyrimidine antimetabolites such as gin, antifolate antimetabolites such as methotrexate and aminopterin, glutamine antimetabolites such as azaserine and DON (6-azido-5-oxo-L-norleucine), vinca alkaloids such as vinblastine and vincristine, Epipodophyllotoxin derivatives such as VM26 and VP16-213, colchicine derivatives such as colchicine and demecoltin, and antibiotics such as actinomycin D, mitomycin C, chromomycin A3, bleomycin, daunorubicin and doxorubicin can be used.

  Examples of immunosuppressants include corticosteroids such as prednisolone, methylprednisolone, and hydrocortisone, alkylating agents such as cyclophosphamide, busulfan, and chlorambucil, and purine antimetabolites such as 6-mercaptopril and azathioprine, Adenosine deaminase inhibitors such as pentostatin, pyrimidine antimetabolite such as 6-azauracil, antifolate antimetabolite such as methotrexate, glutamate antimetabolite such as azotomycin, antibiotics such as daunomycin, adriamycin and mitaramicin, cytochalasin B Cell division inhibitor such as can be used.

  In the case of using the drug as described above, it is desirable that the filler contains a polymer having a function of holding the drug. When such a polymer is contained in the filler together with the drug, the release rate and the release amount of the drug from the stent 1 can be set as desired by adjusting the type and amount of the polymer when the stent 1 is in use. can do.

  It is desirable that the aforementioned polymer is mainly composed of a bioabsorbable polymer. By using the bioabsorbable polymer, the stent 1 can be excellent in safety to the living body when the stent 1 is in use.

  Examples of the cells accommodated in the gap 11A2 between the microprojections 11A1 include cells constituting the inner wall of the applied tubular organ, or stem cells before differentiation into these cells, recombinant plasmids (recombinant vectors). Host cells can be used.

  Examples of the biological substance contained in the gap 11A2 between the microprotrusions 11A1 include nucleic acids such as nucleotides, cDNA, and RNA, amino acids, peptides, and proteins.

  In such a stent 1, the linear portions 11 are integrally formed by a method as described later. Thereby, the strength of the stent 1 as a whole is further improved. In FIG. 2B, for convenience of explanation, an interface exists between the inner peripheral portion 11A and the outer peripheral portion 11B, but this interface may or may not exist.

  As at least one of the constituent material of the inner peripheral portion 11A and the constituent material of the outer peripheral portion 11B (hereinafter referred to as the constituent material of the stent 1), it is desirable to use the following materials depending on the type of the stent 1 . The constituent material of the inner peripheral part 11A and the constituent material of the outer peripheral part 11B may be the same or different.

  The stent 1 of the present invention can be applied to both a balloon-expandable stent and a self-expandable stent. However, since the stent 1 has the microprotrusions 11A1 on the inner surface as described above, the balloon-expandable stent When applied to a type stent, the effect is remarkable, which is preferable. That is, when the stent 1 is applied to a balloon expandable stent, it can be transported and placed at a desired position in the lumen while stably holding the stent using a balloon catheter.

  When the stent 1 is applied to a balloon-expandable stent, the stent 1 needs to be not deformed by the compressive stress received from the tubular organ in the expanded state. For this reason, it is desirable to use a material for the stent 1 that is hardened by plastic deformation due to expansion and that has relatively high rigidity after expansion. In addition, it is desirable to use a material having high biotissue compatibility and chemical stability.

  As such a material, a material mainly composed of one of Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, Ag, or an alloy containing at least one of them is used. it can.

  Among these, in particular, one containing Au, Pt, Rh, Ru, Pd, Os, Ir or an alloy containing at least one of them is desirable, and Au, Pt, Rh, Ru More preferably, the main material is one of Ir or an alloy containing at least one of Ir. These can impart a work hardening property (work hardening property) by plastic deformation due to expansion, and are excellent in biological tissue compatibility and X-ray contrast properties. Moreover, such an alloy has an advantage that work hardening can be easily controlled by the composition ratio.

  Therefore, by forming the stent 1 with these materials, for example, when the stent 1 is applied to an intravascular stent, thrombus formation can be effectively prevented. Further, since the operation of placing the stent 1 in the lumen of the tubular organ can be performed under X-ray fluoroscopy, the placement operation can be performed more smoothly and accurately.

  On the other hand, when the stent 1 is applied to a self-expanding stent, the stent 1 needs to be able to spontaneously restore its shape. For this reason, it is desirable to use a superelastic alloy, a shape memory alloy or a material with relatively high elasticity as the constituent material of the stent 1.

  Examples of such materials include Ni / Ti alloys, Au / Cd alloys, Cu / Zn alloys, Cu / Al alloys, Fe / Pt alloys, Mn / Cu alloys, Ni / Al alloys, Cu / Cd alloys, Cu・ Al / Ni alloys, Au / Cd / Ag alloys, Ti / Al / V alloys, etc. can be used as the main material.

  Among these, a material mainly composed of Ni / Ti alloy (hereinafter also referred to as NT alloy) is desirable. This is because the material exhibits particularly high elasticity and also has excellent shape memory characteristics.

  Moreover, these materials are excellent in biological tissue compatibility by plating the surface with a noble metal or the like, and also excellent in X-ray contrast properties. Therefore, by forming the stent 1 with these materials, for example, when the stent 1 is applied to an intravascular stent, thrombus formation can be effectively prevented. Further, since the operation of placing the stent 1 in the lumen of the tubular organ can be performed under X-ray fluoroscopy, the placement operation can be performed more smoothly and accurately.

  Note that the shape of the stent is not limited to that described above. For example, in this embodiment, the shape of the opening 10 has a rhombus shape, but is not limited thereto, and may be, for example, a triangle, a rectangle, a square, a pentagon, a hexagon, and other polygons.

  Next, with reference to FIG. 3, a method of using the stent 1 will be described with an example in which a balloon expandable stent is applied to a stenosis portion of a blood vessel.

  (I) First, a guide catheter is percutaneously inserted into a blood vessel (a lumen of a tubular organ) by a well-known Seldinger method, and the distal end thereof reaches the vicinity of the stenosis (target site). On the other hand, as shown in FIG. 3 (a), a stent 1 having a reduced diameter is prepared.

  (II) Then, as shown in FIG. 3 (b), the stent 1 is mounted in a reduced diameter on the outer periphery of the balloon 2A at the tip of the balloon-equipped catheter 2, and the balloon-equipped catheter 2 is attached to the guide catheter. Through into the blood vessels.

  (III) Next, using the guide wire inserted into the balloon-equipped catheter 2 as a guide, the balloon-equipped catheter 2 is further pushed forward, and the stent 1 attached to the distal end thereof is transferred to the stenosis and disposed. At this time, the stent 1 can be stably transported because the minute protrusion 11A1 prevents the stent 1 from slipping with respect to the outer surface of the balloon 2A.

  (IV) In this state, a liquid such as physiological saline is injected into the balloon 2A through the balloon catheter 2, and the balloon 2A is inflated. Thereby, as shown in FIG.3 (c), the outer diameter of the stent 1 gradually expands.

  (V) Further, as shown in FIG. 3 (d), when the balloon 2A is inflated and expanded, the outer diameter of the stent 1 further expands (becomes the expanded diameter state), abuts against the inner wall of the blood vessel, Press the inner wall.

  (VI) After sufficiently expanding the diameter of the stent 1, the liquid in the balloon is extracted to deflate the balloon, and the balloon catheter is extracted from the inner periphery of the stent 1. As a result, the stent 1 can be placed in the blood vessel.

  As described above, the narrowed portion of the blood vessel can be expanded by the stent 1 to prevent or treat myocardial infarction or cerebral infarction.

Next, a method for manufacturing the stent 1 will be described as an example of the method for manufacturing the stent of the present invention.
(First step)
(A) First, as shown in FIG. 4, a cylindrical body 3 having a substantially cylindrical shape is prepared. The tubular body 3 is not limited to a cylindrical shape, and may be a polygonal tubular shape, for example.

  As a constituent material of the cylindrical body 3, a single metal or an alloy such as the constituent material of the stent 1 described above can be used. For example, as the constituent material of the cylindrical body 3, at least one selected from the group consisting of Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, Ag, or at least one of them is used. Including alloys, Ni / Ti alloys, Au / Cd alloys, Cu / Zn alloys, Cu / Al alloys, Fe / Pt alloys, Mn / Cu alloys, Ni / Al alloys, Cu / Cd alloys, Cu / Al / Ni alloys, Materials mainly composed of Au, Cd, Ag alloy, Ti, Al, V alloy, etc. can be used. These are appropriately selected according to the characteristics required of the obtained stent 1.

  A partial cross section of such a cylindrical body 3 is as shown in FIG. 5A to 5C are cross-sectional views corresponding to the cross-sectional view taken along the line AA in FIG.

(Second process)
A network structure is formed on the above-described cylindrical body 3, and a plurality of minute protrusions 11A1 are formed on at least a part of the inner surface thereof. Hereinafter, an example of the second step will be described in detail.

  (B) First, as shown in FIG. 5B, a part of the cylindrical body 3 is removed to form an opening 10 'corresponding to the opening 10 described above. As a result, the remaining portion 31 has a shape corresponding to the linear portion 11, and the net structure 4 having a net structure is obtained while forming a cylindrical shape as a whole.

  As a method for removing a part of the cylindrical body 3 in this manner, for example, laser processing, cutting processing, engraving processing, grinding processing, or the like can be used.

  (C) Next, if necessary, the inner surface of the mesh structure 4, that is, the region where the fine protrusions 11A1 are to be formed is roughened. Thereby, in the step (D) described later, the plating easily grows from the rough convex portions formed on the inner surface of the mesh structure 4, and the minute protrusions 11A1 can be formed relatively easily.

  The surface roughening method is not particularly limited. For example, a method of scratching with a file to roughen the surface, sandblasting, blasting such as shot blasting, laser processing, solvent of acid solution or alkali solution is used. Of these chemical treatments, one type can be used alone or two or more types can be used in combination. Such rough surface processing can be performed, for example, while masking unnecessary portions for processing. In the present embodiment, masking is performed so as to cover the outer surface of the mesh structure 4.

  The surface roughness of the rough surface obtained by this rough surface processing is determined according to the abundance of the microprotrusions 11A1, but is preferably in the range of 2 μm to 20 μm, more preferably in the range of 5 μm to 10 μm. Is more desirable. Thereby, it is possible to obtain the minute protrusion 11A1 having a desired abundance more easily and reliably. Here, the surface roughness refers to that measured in accordance with JIS B0601.

  Such roughening may be performed on the inner surface of the cylindrical body 3 before the step (B) described above.

  (D) Next, as shown in FIG. 5C, a plating layer 5 having minute protrusions 11A1 is formed on the inner surface of the mesh structure 4 by using a plating method. As a result, the remaining portion 31 is the outer peripheral portion 11B and the plated layer 5 is the inner peripheral portion 11A, and the stent 1 having the minute protrusions 11A1 is obtained.

  As a method for forming the plating layer 5, for example, a physical vapor deposition method such as a vacuum deposition method or a sputtering method, a chemical vapor deposition method, a plating method such as electrolytic plating or electroless plating can be used. When the plating layer 5 is formed using such a method, it is possible to mask unnecessary portions of the plating with a resist material or the like. In the present embodiment, masking is performed so as to cover the outer surface of the mesh structure 4.

  In particular, electrolytic plating can be suitably used as a plating method. If electrolytic plating is used, the setting of plating conditions is relatively simple, so that the desired minute protrusion 11A1 can be stably formed.

In addition, after this step (D), the stent 1 may be subjected to heat treatment as necessary, so that at least the interface between the inner peripheral portion 11A and the outer peripheral portion 11B may be diffusion bonded or alloyed.
The stent 1 can be obtained as described above.

  Note that the present invention is not limited to the above-described embodiment, and it goes without saying that various modifications can be made without departing from the spirit of the present invention.

  For example, in the above-described embodiment, a plurality of microprojections are formed over the entire inner surface of the stent. However, if a plurality of microprojections are formed on at least a part of the inner surface of the stent, the effect of the present invention is achieved. Obtainable.

  In the above-described embodiment, a plurality of microprojections are formed only on the inner surface of the stent. However, a plurality of microprojections may be formed on the outer surface of the stent.

  In addition, regarding the method for manufacturing the stent, in the above-described embodiment, the microprojections are formed after forming the mesh structure on the cylindrical body 3, but the plating layer having the microprojections on the inner surface of the cylindrical body 3 After forming, the plated layer may be processed together with the cylindrical body 3 to form a network structure.

  Further, the method for forming the minute protrusions is not limited to the method using the plating method as described above. For example, the microprojections may be formed on the cylindrical body 3 by using a method such as blasting, laser processing, or chemical processing.

  In addition, the stent of the present invention is not limited to the manufacturing method using a cylindrical body as described above, but a plate-like metal is used, and a mesh structure or microprojections are formed on the metal, and the stent is formed into a cylindrical shape. Can also be manufactured.

(Example 1)
First, a cylindrical cylindrical body made of Au having a thickness of 50 μm, a length of 20 mm as a core material, and an outer diameter of 1000 μm was prepared, and a mesh structure as shown in FIG. A network structure was formed. The width of the linear part (remainder) of this network structure was 100 μm.

  Next, the portion excluding the inner surface of the network structure, that is, the outer surface, was masked with a resist material, and in this state, roughening was performed by sandblasting. At this time, the surface roughness of the formed rough surface was 7 μm.

  Thereafter, a plated layer having a thickness of 50 μm made of Au was formed on the inner surface of the network structure by wet plating while the masking was performed.

At this time, in the wet plating, a gold concentration: 10 g / l, pH: 6.0, liquid temperature: 65 ° C., an electric salt: citric acid gold plating solution was used as a plating solution, and a platinum plating titanium electrode was used as an anode. . Then, wet plating was performed at a current density of 0.5 A / dm ² while stirring the bath.

Then, the masking was removed to obtain a stent having a plurality of microprojections. In the obtained stent, a plurality of needle-like microprojections are formed over the entire inner surface, the average width of the microprojections is 8 μm, and the average height of the microprojections is 15 μm. There were about 110000 microprojections per mm ^{2 on} the inner surface of the stent. A micrograph showing the state of the microprotrusions is shown in FIG.

(Example 2)
A stent was obtained in the same manner as in Example 1 except that the plating conditions of the plating layer were different.

At this time, in the wet plating, a gold concentration: 6 g / l, pH: 6, liquid temperature: 67 ° C., an electric salt: citric acid gold plating solution was used as a plating solution, and a platinum plating titanium electrode was used as an anode. . Then, wet plating was performed at a current density of 0.5 A / dm ² while stirring the bath.

The obtained stent has a plurality of branch-shaped microprojections formed over the entire inner surface, the average width of the microprojections is 6 μm, and the average height of the microprojections is 10 μm. There were 1000 microprojections per mm ^{2 on} the inner surface of the stent.

(Example 3)
A stent was obtained in the same manner as in Example 1 except that the plating conditions of the plating layer were different.

At this time, in the wet plating, a gold concentration: 5 g / l, pH: 6, liquid temperature: 70 ° C., an electric salt: citric acid gold plating solution was used as a plating solution, and a platinum plating titanium electrode was used as an anode. . Then, wet plating was performed at a current density of 0.4 A / dm ² while stirring the bath.

In the obtained stent, a plurality of scaly microprojections are formed over the entire inner surface, the average width of the microprojections is 10 μm, and the average height of the microprojections is 4 μm. There were 10,000 microprojections per 1 mm ^{2 on} the inner surface of the stent. Further, a micrograph showing the state of the microprotrusions is shown in FIG. 6 (b).

(Comparative example)
A stent was obtained in the same manner as in Example 1 except that the plating conditions of the plating layer were different.

At this time, for the wet plating, a gold concentration: 4.5 g / l, pH: 4.5, liquid temperature: 55 ° C., an electric salt: citric acid gold plating solution is used as a plating solution, and a platinum plating titanium electrode is used as an anode. It was. Then, wet plating was carried out at a current density of 0.25 A / dm ² while stirring the bath.
On the inner surface of the obtained stent, no microprojections were formed, and it was flat.

  When the stents of the examples and comparative examples described above were inserted and placed in an artificial blood vessel using a balloon catheter, the stents of the examples did not slip on the outer surface of the balloon, and the stents of the comparative examples Compared to the above, it was possible to transport and indwell to a desired position in the artificial blood vessel. In the stents of the examples, after filling the gap between the microprotrusions with an antithrombotic agent as a filler, it was inserted and placed in an artificial blood vessel. In both cases, the filler was gradually released from the stent. Was confirmed.

The side view which shows embodiment of the stent which concerns on this invention. Sectional drawing in the AA line shown in FIG. The figure explaining the usage method of the stent shown in FIG. The figure explaining the manufacturing method of the stent shown in FIG. The figure explaining the manufacturing method of the stent shown in FIG. The microscope picture which shows the mode of the inner surface of the stent of this invention.

Explanation of symbols

1 …… Stent
10 …… Opening
11 …… Linear part (wire)
11A …… Inner circumference
11A1 …… Micro protrusion
11A2 …… Gap
11B …… Outer periphery
111 …… Intersection
2 …… Catheter with balloon
2A …… Balloon
3 …… Tubular body
31 …… Balance
4 ... Mesh structure
5 …… Plating layer

Claims (17)

A stent that is inserted into and placed in the lumen of a living tubular organ, has a plurality of openings, and has a cylindrical shape as a whole, and has a plurality of microprojections in at least a part of the inner surface thereof. A stent characterized by that.   The stent according to claim 1, wherein each microprotrusion has one of a needle shape, a branch shape, and a scale shape. 3. The stent according to claim 1, wherein the microprotrusions are present in a range of 5000 or more and 200000 or less per 1 mm ^{2 in the} region.   The stent according to any one of claims 1 to 3, wherein an average height of the microprojections is in a range of 5 µm to 50 µm.   The stent according to any one of claims 1 to 4, wherein an average width of the microprojections is in a range of 0.5 µm to 30 µm.   The stent according to any one of claims 1 to 5, wherein a filler is filled between the microprotrusions.   The stent according to claim 6, wherein the filler contains a drug.   The drug mainly comprises one of antithrombotic agents, antiplatelet agents, immunosuppressive agents, cytostatic agents, anti-inflammatory agents, and endothelial healing promoters alone or in combination of two or more. The stent according to claim 7.   The stent according to claim 7 or 8, wherein the filler contains a polymer having a function of holding the drug.   The stent according to claim 9, wherein the polymer contains a bioabsorbable polymer as a main component.   The stent according to any one of claims 1 to 10, wherein the stent is a balloon expandable stent.   The stent according to claim 11, wherein the microprotrusions have a function of preventing slipping with respect to the outer surface of the balloon when the stent is inserted and placed in the lumen portion.   The stent is composed mainly of at least one selected from the group consisting of Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, and Ag, or an alloy containing at least one of them. The stent according to claim 11 or 12, characterized by the above.   The stent according to any one of claims 1 to 10, wherein the stent is made of a Ni / Ti alloy as a main material. A first step of preparing a tubular body;
A method for manufacturing a stent, comprising: a second step of forming a plurality of openings in the cylindrical body and forming a plurality of microprotrusions in at least a partial region of the inner surface thereof.   16. The stent manufacturing method according to claim 15, wherein, in the second step, the plurality of minute protrusions are formed by a wet plating method and / or a dry plating method. The method for manufacturing a stent according to claim 16, wherein the surface of the cylindrical body is roughened prior to the second step.

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