JP2006130030A - Method for manufacturing stent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for manufacturing a stent capable of precisely controlling a releasing amount and a release rate of a medical agent, or the like, and also controlling a region where the medical agent is released and to reduce an outer diameter as the diameter remains reduced. <P>SOLUTION: First, a groove 31 corresponding to a reticulated structure is formed on an outer surface of a columnar core material 3. A first layer 41 made of a metal as a main material is formed in a manner to fill a part of the groove 31. A second layer 42 is formed on the outer surface of the first layer 41. Next, the first layer 41 and the second layer 42 are formed into a reticulated structure by removing parts of the first layer 41 and the second layer 42 formed in the part other than the groove 31 on the outer surface of the core material 3. Then, a third layer 43 made of a metal as a main material is formed on the first and second layers 41, 42. A hollow linear part is formed with the first and third layers 41, 43 by removing the core material 3 and the second layer 42. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

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

  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 is generally cylindrical as a whole and has a network structure. Then, such a stent is introduced into the lumen of the tubular organ by contracting the opening defined by the plurality of linear portions constituting the mesh structure and moving the lumen. Then, in the indwelling part, it is fixed (mounted) by widening the opening and making the diameter expanded.

  In manufacturing such a stent, for example, in Patent Document 1, a plating layer is formed on the outer periphery of a rod-shaped electrode to form a plating layer, and an opening is formed in the plating layer by a processing device such as cutting or laser processing. After forming the plated layer into a network structure by forming, the electrode is removed to obtain a stent.

  On the other hand, as one of the treatment methods using a stent, a local pharmacological treatment can be performed by loading a drug on the stent, attaching the stent to a treatment site of a tubular organ, and releasing the drug. (For example, refer to Patent Document 2).

  For example, in Patent Document 2, a stent body is coated with a polymer for impregnating a drug. In this type of stent, when the stent is mounted in the lumen of the tubular organ, the drug impregnated in the polymer is gradually released into the body fluid, and the therapeutic effect is maintained for a certain period.

JP 2003-102847 A JP 2002-345972 A

  When the stent is in a reduced diameter state, it is desirable to make the size of the opening as small as possible in order to sufficiently reduce the outer diameter when the stent is in a reduced diameter state.

  However, in the method according to Patent Document 1, since the shape of the opening depends on the size of a tool (cutting tool) used for processing the plating layer, it is difficult to form a very small opening in the plating layer. As a result, a gap generated between the linear portions when the stent is in a reduced diameter state is also increased, so that the opening cannot be sufficiently reduced, and the outer diameter in the reduced diameter state of the stent is sufficiently reduced. It is difficult.

  On the other hand, in the stent according to Patent Document 2, the release of the drug from the polymer is caused by the diffusion of the drug impregnated into the polymer into the body fluid. It is difficult to precisely control the amount and release rate. For this reason, the stent using this polymer has a problem that a sufficient therapeutic effect cannot be obtained.

  Accordingly, the present invention solves the above-mentioned problems, and an object of the present invention is to form a stent capable of precisely controlling the release amount, release rate, and release site of a drug and the like, and relatively easily reduce the shrinkage. An object of the present invention is to provide a stent manufacturing method capable of reducing the outer diameter in the diameter state.

In order to solve the above problems, the stent manufacturing method of the present invention is a stent manufacturing method used by being inserted and placed in the lumen of a biological tubular organ,
When producing a metal molded body having a hollow linear portion constituting a network structure as a whole,
A first step of forming a groove corresponding to the mesh structure on the outer surface of a cylindrical or columnar core material;
A second step of forming, on the outer surface of the core material, a first layer composed of a metal as a main material so as to fill a part of the groove, with a thickness smaller than the depth of the groove;
A third step of forming a second layer on the outer surface of the first layer;
By removing the first layer and the second layer formed in a portion other than the groove on the outer surface of the core material, the first layer and the second layer form the network structure. A fourth step to be considered,
A fifth step of forming a third layer composed mainly of metal on the first layer and the second layer; and
And removing the second layer to form the hollow linear portion by the first layer and the third layer, and a sixth step of removing the core material. . According to the present invention, since the stent can be obtained in a shape corresponding to the groove formed in the core material, the opening of the network structure is extremely small without depending on the size of the tool (blade) used for processing. it can. As a result, the outer diameter in the reduced diameter state can be sufficiently reduced relatively easily.

  Further, according to the present invention, since the hollow portion is formed in the stent, the weight of the strut can be reduced while maintaining the mechanical strength necessary for the use of the strut.

  Further, the elasticity, bendability, etc. of the strut can be changed by changing the size, shape, position, etc. of the hollow portion without changing the material constituting the strut.

  In addition, when the stent is in use, the strut can be gradually discharged from the small hole to the outside of the stent if the hollow portion is filled with the filler. And according to the magnitude | size of a small hole, a number, a position, etc., the discharge | release amount, discharge | release speed | rate, and discharge | release site | part of a filler can be adjusted. Accordingly, it is possible to form a stent capable of precisely controlling the release amount, release rate, and release site of a filler such as a drug.

  In the present invention, in the sixth step, the core is almost simultaneously with the removal of the second layer and the formation of the hollow linear portion by the first layer and the third layer. It is desirable to remove the material. According to this invention, the manufacturing process of a stent can be simplified.

  In the present invention, in the sixth step, after the core material is removed, the second layer is removed, and the hollow linear portion is formed by the first layer and the third layer. Is desirable. According to this invention, the method for removing the core material and the method for removing the second layer can be appropriately selected according to the material constituting the core material and the material constituting the second layer.

  In the present invention, in the sixth step, the core material is removed after the second layer is removed and the hollow linear portion is formed by the first layer and the third layer. Is desirable. According to this invention, the method for removing the core material and the method for removing the second layer can be appropriately selected according to the material constituting the core material and the material constituting the second layer.

  In the present invention, in the first step, it is desirable that a cross-sectional shape of the groove has a corner. According to this invention, a groove can be formed in the core material relatively easily.

  In the present invention, the corner is preferably rounded. According to this invention, the edge portion of the obtained stent can be rounded without being processed in a separate step.

  In the present invention, the metal constituting the first layer and the metal constituting the third layer are preferably the same type. According to the present invention, the first layer and the second layer can be firmly joined by a relatively simple method.

  In the present invention, after the fifth step, there is a bonding step of performing diffusion bonding at least the first layer and the third layer by performing a heat treatment on the first layer and the third layer. It is desirable. According to the present invention, the first layer and the second layer can be firmly bonded more reliably.

  In the present invention, in the fifth step, it is desirable to form the third layer by electrolytic plating using the first layer and the second layer as electrodes. According to this invention, the manufacturing process of a stent can be simplified.

  In the present invention, after the fifth step, at least one of the first layer and the third layer communicates with a space defined by the first layer and the third layer. It is desirable to have a hole forming step for forming a through hole. According to the present invention, the size, number, position, etc. of the small holes can be adjusted relatively easily. As a result, it is easy to adjust the discharge amount, release speed, and release site of the filler.

  In the present invention, it is desirable that the hollow portion is filled with a filler after the sixth step. According to the present invention, when the stent is in use, since a filling material such as a medicine accommodated in the hollow portion is released from the small hole to the outside of the stent, according to the size, number, position, etc. of the small hole, The discharge amount, release rate, and release site of the filler can be adjusted. Accordingly, it is possible to form a stent capable of precisely controlling the release amount, release rate, and release site of a filler such as a drug.

  In the present invention, it is desirable that the filler contains at least one of a drug, a cell, and a biological substance. According to the present invention, safer treatment can be performed.

  According to the present invention, it is possible to form a stent capable of precisely controlling the release amount, release rate, and release site of a drug and the like, and relatively easily reduce the outer diameter in a reduced diameter state. A stent can be obtained.

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

  First, prior to the description of the stent manufacturing method of the present invention, a stent obtained by such a manufacturing method 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.

  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 stent 1 has a network structure formed by connecting a plurality of plate-like linear portions 11. An opening 10 is formed in a portion surrounded by a plurality of linear portions (struts) 11. The opening 10 contracts as the linear portion 11 is bent, and the stent 1 is brought into a reduced 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.

  Here, in this specification, “axial flexibility” refers to flexibility in the direction of the arrow in FIG. 1 (ease of bending, that is, flexibility).

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.

  Here, the average cross-sectional area of the linear portion 21 refers to the area of a region surrounded by the outline of the outer periphery of the cross section of the linear portion 21.

  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.

  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 addition, the stent 1 is hollow in each linear portion 11 along the longitudinal direction of the linear portion 11 as shown in FIG. 2 (b) which is a partially enlarged view of FIG. 2 (a). A portion 113 is formed. That is, the linear portion 11 has a hollow linear shape. The hollow portion 113 serves as a storage portion that stores a filling such as a medicine.

  One wall portion of the stent 1 has a plurality of small holes 112 scattered in the extending direction of each linear portion 11, and each small hole 112 communicates with the hollow portion 113.

Each small hole 112 is opened in the radial direction toward the outer peripheral side of the stent 1.
The stent 1 is inserted and placed in the lumen of the tubular organ such that the wall in which the small holes 112 are formed faces the inner wall of the tubular organ, for example.

  When the stent 1 is inserted and placed in the lumen portion, the filling material such as the medicine accommodated in the hollow portion 113 is released from the small hole 112, and the therapeutic effect or the like is stopped until the release of the medicine or the like stops. Persists.

  In such a stent 1, the release amount and release period (release rate) of the drug and the like can be precisely controlled by adjusting the volume and shape of the hollow portion 113 and the size, number and pitch of the small holes 112.

  Further, by adjusting the attachment site of the stent 1 and the size, number, and pitch of the small holes 112, the drug release site can be limited to a specific site of the tubular organ. Therefore, a higher therapeutic effect or the like can be obtained at the site to be treated.

  Further, the small hole 112 has a portion whose cross-sectional area gradually decreases toward the hollow portion 113. Such a small hole 112 can be formed relatively easily, and the filling material can be discharged from the small hole 112 in a relatively wide range.

  Further, by adjusting the inclination of the gradually decreasing portion with respect to the axis of the small hole 112, the discharge amount and discharge speed of the packing can be adjusted relatively easily.

  Further, in the stent 1, it is also possible to form small holes (not shown) by opening both ends of the hollow portion 113 to the outside.

  When the stent 1 is inserted and placed in the lumen part of the tubular organ, the filling such as a medicine accommodated in the hollow part 113 is also released from the small holes at both ends into the lumen part.

  In the stent 1 having such a hollow portion 113, the discharge amount and release speed of a filling such as a drug can be precisely controlled by adjusting the volume and shape of the hollow portion 113 and the size of the small holes 112 and the like. .

  As described above, the discharge amount and release speed of the filling material of the stent 1 and the release site are controlled by the size and shape of the hollow portion 113 and the size of the small hole 112 and the like.

  Accordingly, these parameters of the hollow portion 113 and the small hole 112 are appropriately set according to the desired release amount, release rate, and release site of the drug and the like, but are preferably in the following ranges.

First, the average cross-sectional area of the hollow portion 113 is preferably in the range of 50 [mu] m ² or more 0.03 mm ² or less, and more desirably in the range of 80 [mu] m ² or more 0.01 mm ² or less.

  If the cross-sectional area of the hollow part 113 is too small, the drug is difficult to flow depending on the viscosity of the drug, the desired release amount of the drug and the like may not be obtained, and if the cross-sectional area of the hollow part 113 is too large, Depending on the cross-sectional area of the linear portion 11, the rigidity of the stent 1 may be reduced.

Further, when the average cross-sectional area of the linear portion 11 is S1 [μm ² ] and the average cross-sectional area of the hollow portion 113 is S2 [μm ² ], it is preferable that S2 / S1 is in the range of 0.01 to 0.5.

  Thereby, while ensuring the rigidity necessary for the use of the linear portion 11, the discharge amount, release speed, and release portion of the filling such as a medicine can be precisely controlled.

  Further, the cross-sectional shape of the hollow portion 113 is substantially constant over almost the entire stent 1.

  Thereby, the softness | flexibility (flexibility) of the axial direction of the stent 1 can prevent becoming non-uniform | heterogenous in each part.

Note that the cross-sectional shape of the hollow portion 113 may be different in each portion of the stent 1.
Further, the cross-sectional shape of the hollow portion 113 may be a quadrangle (rectangular shape) as shown in FIG.

  When the cross-sectional shape of the hollow portion 113 is a quadrangle, the width and height are preferably in the range of 8 μm to 150 μm, respectively.

  Further, the hollow portion 113 only needs to be formed in at least a part of the stent 1, and may be formed over the entire stent 1 or only in a part of the stent 1.

The average cross-sectional area of the small holes 112 is preferably in the range of 0.10 .mu.m ² or 0.002 mm ² or less, more preferably in the range of 0.20 [mu] m ² or more 0.001 mm ² or less.

  If the average cross-sectional area of the small holes 112 is too small, it may be difficult to release the drug depending on the viscosity of the drug, and a desired release amount of the drug or the like may not be obtained.

  Further, if the average cross-sectional area of the small holes 112 is larger than the above range, it becomes difficult to finely control the discharge amount and the discharge site depending on the size of the small holes 112.

  Note that the cross-sectional shape of the small holes 112 may be, for example, a circle (rectangular shape) or a polygon such as a circle, an ellipse, a square, a diamond, a triangle, a pentagon, and a hexagon.

  In the present embodiment, the small holes at both ends of the stent 1 may be closed, or may be formed at either one of the both ends of the hollow portion 113. That is, one end of the hollow portion 113 may be closed and a small hole may be formed only at the other end.

  As the constituent material of the stent 1, it is desirable to use the following materials according to the type of the stent 1.

  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, an alloy mainly containing one or two of Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, Ag and the like can be used.

  Among these, in particular, an alloy mainly composed of one or two of Au, Pt, Rh, Ru, Pd, Os, and Ir is desirable, Au, Pt, Rh, Ru, Ir More preferred is an alloy mainly composed of one or two of them. These are capable of imparting a work hardening property (work hardening) 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 alloy, Au / Cd / Ag alloy, Ti / Al / V alloy, etc. can be used.

  Of these, those mainly composed of Ni / Ti alloys (hereinafter also referred to as NT alloys) are 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 and 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.

  The hollow portion 113 may contain a carrier for (temporarily) carrying a filler to be described later. Thereby, the discharge | release speed | rate of a filler can be controlled more precisely.

  As the carrier, it is desirable to use a substance that gradually dissolves upon contact with a porous body or body fluid. Thereby, the discharge rate of the packing can be controlled more precisely and relatively easily.

  Examples of the carrier include polycaprolactone, poly DL lactic acid, poly L lactic acid, polyglycolic acid, polyglactin (copolymer of polyglycolic acid and polylactic acid), polydioxanone, polyglycolate (trimethylene carbonate). And glycolide), polyglycolic acid or polylactic acid and ε-caprolactone copolymer, lactide, polyorthoester, polyiminocarbonate, aliphatic polycarbonate, polyphosphazene, etc. The above can be used.

  The carrier may be provided as necessary, and may not be provided when the biocompatibility of the carrier itself is concerned.

  As the filler contained in the hollow portion 113, at least one of a drug, a cell, and a biological substance can be used.

  The drug accommodated in the hollow portion 113 is selected according to the type of tubular organ in which the stent 1 is placed, and examples thereof include an antithrombotic agent, an analgesic / sedative agent, an antiproliferative agent, an anticancer agent, and an immunosuppressive agent. Can be used.

  Such a medicine is accommodated in the hollow portion 113 and gradually released to the outside of the stent 1 during use, and exhibits various therapeutic effects.

  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 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 include somatostatin or a homologue thereof, nitroprusside, colchicine, fish oil (ω3 fatty acid), steroid agent, serotonin antagonist, calcium groove blocking antibody, hestamine antagonist, enzyme inhibitor (eg, angiotensin) Converting enzyme inhibitor, prostaglandin synthase inhibitor, HMG-CoA reductase inhibitor, phosphodiesterase inhibitor, thiol protease inhibitor, methotrexate), growth factor antagonist (eg, fibroblast growth factor antagonist, platelet derived) Growth factor antagonists), nitric oxide, and the like can be used.

  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.

  As the cells accommodated in the hollow portion 113, for example, cells constituting the inner wall of the applied tubular organ, or stem cells before differentiation into the cells, host cells into which a recombinant plasmid (recombinant vector) has been introduced can be used. .

  Examples of the biological material contained in the hollow portion 113 include nucleic acids such as nucleotides, cDNA, and RNA, amino acids, peptides, and proteins.

  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.

  In this embodiment, the connecting portion (near the intersection 111) between the linear portions 11 is bent. However, the connecting portion may be curved such as an arc shape (U shape).

  Next, a method of using the stent 1 will be described by taking a case where a balloon expandable stent is applied to a stenosis portion of a blood vessel as an example.

  (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).

  (II) Then, the stent 1 is mounted on the outer periphery of the balloon at the distal end of the balloon-attached catheter in a reduced diameter state, and the balloon-attached catheter is guided into the blood vessel through the guide catheter.

  (III) Next, using the guide wire inserted into the catheter with balloon as a guide, the catheter with balloon is further pushed forward, and the stent 1 attached to the distal end thereof is transferred to the stenosis and arranged.

  (IV) In this state, a liquid such as physiological saline is injected into the balloon through the balloon catheter and the balloon is inflated. As a result, the outer diameter of the stent 1 gradually increases.

  (V) Further, when the balloon is inflated and expanded, the outer diameter of the stent 1 is further expanded (becomes the expanded diameter state), abuts against the inner wall of the blood vessel, and presses 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. In addition, when the stent 1 is inserted and placed in the blood vessel in this way, the drug stored in the hollow portion 113 of the stent 1 is released from the small hole 112 and the like, and the therapeutic effect is stopped until the drug release stops. Etc. will last.

Next, a method for manufacturing the stent 1 will be described.
(First step)
(A) First, as shown in FIG. 3A, a substantially cylindrical core material 3 is prepared. The core material 3 may have a substantially pipe shape.

  Desirably, the core material 3 is relatively hard and can be removed relatively easily in the step (E) described later.

  The constituent material of the core material 3 is selected according to the constituent material of the stent 1, but for example, polyolefin (for example, PE, PP, etc.), polyvinyl chloride, polyamide, polyphenylene sulfide, polycarbonate, polymethyl methacrylate Compared with resin materials such as polyether and polyacetal, and other metal materials that constitute the stent 1, such as Ni and Ni alloys, Cu and Cu alloys, Fe and Fe alloys Materials can be used.

  (B) Next, as shown in FIG. 3 (b), a shape corresponding to the linear portion 11 of the stent 1, that is, a mesh-like groove 31 is formed on the peripheral surface of the core material 3.

  As a method for forming the groove 31, for example, cold / hot forging, die casting, injection molding, laser processing, cutting processing, engraving processing, rolling processing, and the like can be used.

  In this step, since the cross-sectional shape of the groove 31 has corners, the groove 31 can be formed in the core material 3 relatively easily.

Further, it is desirable that the corner is rounded. By doing so, the edge portion of the obtained stent 1 can be rounded without being processed in a separate process.
The cross section (partial cross section) of the core material 3 is in a state as shown in FIG.

(Second process)
(C) Next, as shown in FIG. 4C, a first layer 41 made of metal as a main material is formed on the outer peripheral surface of the core material 3. The first layer 41 only needs to be formed on the outer surface of the core member 3 so as to fill a part of the groove 31 in the depth direction. That is, the layer thickness of the first layer 41 only needs to be smaller than the depth of the groove 31.

  As a constituent material of the first layer 41, a single metal or an alloy constituting the alloy of the stent 1 described above can be used. For example, the constituent material of the first layer 41 includes Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, Ag, or an alloy mainly composed of at least two of these, Ni / Ti Alloy, Au / Cd alloy, Cu / Zn alloy, Cu / Al alloy, Fe / Pt alloy, Mn / Cu alloy, Ni / Al alloy, Cu / Cd alloy, Cu / Al / Ni alloy, Au / Cd / Ag alloy Ti / Al / V alloy can be used. These are appropriately selected according to the characteristics required of the obtained stent 1.

  Further, the method for forming the first layer 41 is appropriately selected according to the constituent material (main body material) of the stent 1. For example, a physical vapor deposition method such as a vacuum deposition method or a sputtering method, One of a vapor deposition method, a plating method such as electrolytic plating and electroless plating, a liquid film deposition method such as a method by applying (applying) a liquid material (solution or dispersion) including a main body material, or the like Two or more types can be used.

(Third process)
(D) Next, as shown in FIG. 4D, the second layer 42 is formed on the outer peripheral surface of the first layer 41.

  As the constituent material of the second layer 42, the same material as that of the core material 3 described above can be used. That is, as the constituent material of the second layer 42, for example, a resin material such as polyolefin (for example, PE, PP, etc.), polyvinyl chloride, polyamide, polyphenylene sulfide, polycarbonate, polymethyl methacrylate, polyether, polyacetal, In addition, as compared with metal materials constituting the stent 1, such as Ni and Ni alloy, Cu and Cu alloy, Fe and Fe alloy, a metal material that has a natural electrode potential can be used. These are selected according to the constituent material of the stent 1 and the like.

  Further, as a method for forming the second layer 42, the same method as the method for forming the first layer 41 described above can be used.

(4th process)
(E) Next, as shown in FIG. 4 (e), the portions of the first layer 41 and the second layer 42 accommodated in the groove 31 are left along the outer surface of the core material 3. Further, by removing a part of these, the first layer 41 and the second layer 42 have the network structure.

  As a method for removing a part of the first layer 41 and the second layer 42 in this way, for example, laser processing, cutting processing, engraving processing, grinding processing, or the like can be used.

(5th process)
(F) Next, as shown in FIG. 5 (f), a third layer 43 made of a metal as a main material is formed on the first layer 41 and the second layer 42.

  As the constituent material of the third layer 43, the same material as that of the first layer 41 described above can be used. That is, as the constituent material of the third layer 43, for example, Au, Pt, Ta, Rh, Ru, Pd, Nb, Os, Ir, Ag, or an alloy mainly composed of at least two of these, Ni,・ Ti alloy, Au / Cd alloy, Cu / Zn alloy, Cu / Al alloy, Fe / Pt alloy, Mn / Cu alloy, Ni / Al alloy, Cu / Cd alloy, Cu / Al / Ni alloy, 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.

  Further, as a method for forming the third layer 43, the same method as the method for forming the first layer 41 described above can be used. That is, the method for forming the third layer 43 is appropriately selected according to the constituent material (main body material) of the stent 1, but for example, a physical vapor deposition method such as a vacuum deposition method or a sputtering method, One of a vapor deposition method, a plating method such as electrolytic plating and electroless plating, a liquid film deposition method such as a method by applying (applying) a liquid material (solution or dispersion) including a main body material, or the like Two or more types can be used.

  It is desirable that the metal constituting the first layer 41 and the metal constituting the third layer 43 be the same type. By doing so, the first layer 41 and the third layer 43 can be firmly joined by a relatively simple method.

  In this step, it is desirable to form the third layer 43 by electrolytic plating using the first layer 41 and the second layer 42 as electrodes. By doing so, the manufacturing process of the stent 1 can be simplified.

  The third layer 43 is formed by forming a metal layer uniformly on the first layer 41, the second layer 42, and the core material 3, and then removing a part thereof by etching or the like. May be.

  (G) Next, as shown in FIG. 5 (g), a hole 43 a communicating with the second layer 42 is formed in the third layer 43 at a position corresponding to the small hole 112. This step may be performed after step (H) described later.

  Thus, after the step (F) (fifth step), the third layer 43 is provided with a hole 112 as a through-hole communicating with the space defined by the first layer 41 and the third layer 43. A hole forming step to be formed; By so doing, the size, number, position, etc. of the small holes 112 can be adjusted relatively easily. As a result, it is easy to adjust the discharge amount, release speed, and release site of the filler.

  In the present embodiment, the elution time of the second layer 42 can be shortened in the step (H) by forming the holes 43a before the step (H).

  As a method for forming the hole 43a, for example, one of a dry etching method, a wet etching method, an electrolytic etching method, an electric discharge machining, a fine powder blasting method, laser machining, machining by a machining center, etc., engraving machining by an engraving machine, etc. Or two or more can be used.

(Sixth step)
(H) Next, the core material 3 and the second layer 42 are removed to obtain the stent 1 as shown in FIG.

  In this step, since the second layer 42 and the core material 3 are removed almost simultaneously, the manufacturing process of the stent can be simplified.

  The method for removing the core material 3 and the second layer 42 is appropriately selected depending on the constituent materials of the core material 3 and the second layer 42. For example, a method of burning off by heating (a method of burning off), a stent A method in which the core material 3 is dissolved in a solvent that can be selectively dissolved without dissolving or swelling 1; a method in which the core material 3 is selectively eluted by chemical etching or an electrochemical technique; It is possible to use a method of releasing the mold.

  Note that the removal time of the core material 3 and the removal time of the second layer 42 may be different. That is, after the core material 3 is removed, the second layer 42 may be removed to form a hollow linear portion by the first layer 41 and the third layer 43, or the second layer The core material 3 may be removed after forming the hollow linear portion by the first layer 41 and the third layer 43 by removing 42.

  By doing in this way, according to the constituent material of the core material 3 and the constituent material of the second layer 42, the removal method of the core material 3 and the removal method of the second layer 42 can be appropriately selected. .

  (I) If necessary, at least the first layer 41 and the third layer 43 are diffusion-bonded by performing a heat treatment on the first layer 41 and the third layer 43 (bonding step). As a result, the first layer 41 and the third layer 43 can be firmly bonded more reliably. At this time, at the interface between the first layer 41 and the third layer 43, while also serving as low-temperature strain relief annealing for the purpose of removing the internal stress of each layer of the first layer 41 and the third layer 43, The processing is performed so that the constituent materials between the layers diffuse to each other. As a result, the interface between the first layer 41 and the third layer 43 disappears, the strength of the stent 1 increases, and delamination between the first layer 41 and the third layer 43 is prevented.

  When this heat treatment is performed, the heating atmosphere is preferably a non-oxidizing atmosphere, that is, an inert atmosphere such as a nitrogen atmosphere or an argon atmosphere, or a reducing atmosphere such as hydrogen or ammonia decomposition gas. The heating temperature is preferably in the range of 300 ° C. to 1500 ° C., and more preferably in the range of 500 ° C. to 1200 ° C. The heating time is preferably in the range of 0.5 hours to 3 hours, more preferably in the range of 1.0 hours to 2 hours. By performing the heat treatment under such conditions, the first layer 41 and the third layer 43 are more reliably alloyed (linearly) while preventing the oxidation of the first layer 41 and the third layer 43. Part 11 can be formed).

(J) Next, the edge of the stent 1 is rounded as necessary.
As this processing method, for example, polishing, barrel polishing, electrolytic polishing, chemical polishing, honing, electromagnetic barrel polishing and the like can be used.

As described above, the stent 1 shown in FIGS. 1 and 2 is obtained.
According to such a manufacturing method of the stent 1, since the stent 1 can be obtained in a shape corresponding to the groove 31 formed in the core material 3, it does not depend on the size of a tool (blade) used for processing. In addition, the opening 10 of the mesh structure can be made extremely small. As a result, the outer diameter in the reduced diameter state can be sufficiently reduced relatively easily. Further, since the width of the opening 10 of the mesh structure in the circumferential direction of the stent 1 corresponds to the size of the portion other than the groove 31 on the outer surface of the core material 3, the width of the opening 10 can be made sufficiently small. . As a result, the outer diameter of the stent 1 can be reduced.

  In addition, the manufacturing method of the stent of this invention is not limited to the above-mentioned embodiment, Of course, it can add variously within the range which does not deviate from the meaning of this invention.

(Example 1)
First, a cylindrical column made of ABS resin having a length of 20 mm and an outer diameter of 2050 μm is prepared as a core, and a groove having a mesh structure as shown in FIG. did. The groove had a substantially rectangular cross-sectional shape, and was 100 μm wide and 80 μm deep.

  Next, an 18 gold Au—Cu alloy plating layer having a thickness of 20 μm was formed on the outer peripheral surface of the above-described cylindrical member with grooves formed by wet plating after Ni subbing plating.

  Next, an Fe plating layer having a thickness of 20 μm was formed on the outer surface of the 18 gold Au—Cu alloy plating layer by wet plating.

  Next, along the outer surface of the cylindrical member, portions other than the groove on the outer surface of the cylindrical member are ground by grinding so as to leave a portion in the groove of the Au-Cu alloy layer and the Fe plating layer. The Au—Cu alloy layer and the Fe plating layer formed in the above were removed. As a result, a structure was obtained in which the Au—Cu alloy layer and the Fe plating layer formed the network structure in the grooves of the cylindrical column made of ABS resin.

  Next, the above Au-Cu alloy layer and Fe plating layer are used as electrodes, and the structure is subjected to electrolytic plating, so that 18 μm thick 18 μm thick is selectively formed on the Au—Cu alloy layer and Fe plating layer. A gold Au-Cu alloy plating layer was formed.

  The obtained Au—Cu alloy plating layer was drilled with a diameter of about 10 μm and a depth of 25-30 μm by UV laser processing to form small holes as shown in FIG.

Next, the Fe plating layer was selectively eluted by an electrochemical method from the structure formed by forming the Au—Cu alloy layer and the Fe plating layer on the columnar material. Further, the ABS resin was thermally decomposed by heat treatment at 700 ° C. for 2 hours in an H ₂ atmosphere. This obtained the stent which has a hollow part.

1 is a side view showing a first embodiment of a stent according to the present invention. Sectional drawing in the AA line 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 figure explaining the manufacturing method of the stent shown in FIG.

Explanation of symbols

1 …… Stent
10 …… Opening
11 …… Linear part (wire)
111 …… Intersection
112 …… Small hole
113 …… Hollow part
3 …… Core
31 …… Groove
41 …… First layer
42 …… Second layer
43 …… Third layer
43a …… hole

Claims (12)

A method of manufacturing a stent that is used by being inserted and placed in a lumen of a living tubular organ,
When producing a metal molded body having a hollow linear portion constituting a network structure as a whole,
A first step of forming a groove corresponding to the mesh structure on the outer surface of a cylindrical or columnar core material;
A second step of forming, on the outer surface of the core material, a first layer composed of a metal as a main material so as to fill a part of the groove, with a thickness smaller than the depth of the groove;
A third step of forming a second layer on the outer surface of the first layer;
By removing the first layer and the second layer formed in a portion other than the groove on the outer surface of the core material, the first layer and the second layer form the network structure. A fourth step to be considered,
A fifth step of forming a third layer composed mainly of metal on the first layer and the second layer; and
And removing the second layer to form the hollow linear portion by the first layer and the third layer, and a sixth step of removing the core material. A method for manufacturing a stent.   In the sixth step, the second layer is removed, and the core material is removed substantially simultaneously with the formation of the hollow linear portion by the first layer and the third layer. The method of manufacturing a stent according to claim 1.   In the sixth step, after the core material is removed, the second layer is removed, and the hollow linear portion is formed by the first layer and the third layer. The manufacturing method of the stent of Claim 1.   In the sixth step, the core material is removed after the second layer is removed and the hollow linear portion is formed by the first layer and the third layer. The manufacturing method of the stent of Claim 1.   The stent manufacturing method according to any one of claims 1 to 4, wherein, in the first step, the cross-sectional shape of the groove has a corner.   The method for manufacturing a stent according to claim 5, wherein the corner is rounded.   The method for manufacturing a stent according to any one of claims 1 to 6, wherein the metal constituting the first layer and the metal constituting the third layer are of the same type.   After the fifth step, the method includes a bonding step of performing diffusion bonding at least the first layer and the third layer by performing heat treatment on the first layer and the third layer. The method for manufacturing a stent according to any one of claims 1 to 7.   9. The method according to claim 1, wherein in the fifth step, the third layer is formed by electrolytic plating using the first layer and the second layer as electrodes. A method for manufacturing a stent.   After the fifth step, a through hole that communicates with a space defined by the first layer and the third layer is formed in at least one of the first layer and the third layer. The stent manufacturing method according to claim 1, further comprising a hole forming step.   The method for manufacturing a stent according to any one of claims 1 to 10, wherein a filler is filled in the hollow portion after the sixth step. The method for manufacturing a stent according to claim 11, wherein the filling includes at least one of a drug, a cell, and a biological substance.

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