JP2020162778A - Method for manufacturing stent delivery system - Google Patents

Abstract

To provide a method for manufacturing a stent delivery system which suppresses the generation of a pin hole in a balloon where a stent is arranged, makes an outer diameter small, and increases retention of the stent.SOLUTION: A method for manufacturing a stent delivery system includes: an arrangement process (S1) for arranging a folded balloon in a lumen of a stent; a first diameter reduction process (S2) for reducing a diameter of the stent by applying a pressure from the outside in a radial direction of the stent; and a second diameter reduction process (S3) for reducing the diameter of the stent while increasing the pressure inside the balloon to a first pressure and applying a pressure to the stent from the inside in the radial direction of the stent. The first pressure is smaller than a second pressure at which the stent starts expanding.SELECTED DRAWING: Figure 4

Description

The present invention relates to a method for manufacturing a stent delivery system.

Stent placement is performed to secure a lumen by placing a stent in a lesion such as a stenosis formed in a patient's living lumen (for example, a blood vessel). As stents used for stent placement, for example, balloon dilatation type stents (see Patent Document 1) and self-expansion type stents have been developed.

In a balloon-expandable stent, the stent is crimped (held) on the outer surface of the folded balloon. In the stent delivery system described in Patent Document 1, a part of the balloon is sandwiched in the gap between the stents in order to increase the retention of the stent with respect to the balloon.

The method for manufacturing a stent delivery system described in Patent Document 1 employs the following work procedure. First, the operator places a folded balloon in the lumen of the stent. Next, by reducing the diameter of the stent while pressurizing the inside of the balloon, the membrane material of the balloon is projected into the gap between the stents. The operator finishes the diameter reduction process after the outer diameter of the stent reaches the target outer diameter. The stent maintains a part of the balloon sandwiched in the gap even after the diameter reduction step is completed. This increases the retention of the stent with respect to the balloon.

Special Table 2009-540928

When the stent delivery system is manufactured by the above manufacturing method, it is possible to increase the retention of the stent with respect to the balloon, but the following problems may occur.

The portion of the balloon sandwiched in the gap of the stent receives stress from the stent, and pinholes (holes) may be generated in the balloon at the place where the stress is concentrated. As a method of suppressing the occurrence of pinholes in the balloon, for example, it is conceivable to set a large target outer diameter in the diameter reduction step of the stent. By setting a large target outer diameter of the stent, the operator can widen the gap of the stent when the stent reaches the target outer diameter. As a result, the operator can avoid stress concentration on a part of the balloon sandwiched in the gap of the stent.

However, when the target outer diameter in the stent diameter reduction step is set to be large, the stent delivery system has a large stent outer diameter (profile) after the diameter reduction step, and the passability of the lesion portion is lowered. In addition, when the target outer diameter in the stent diameter reduction process is set large, the stent delivery system has an amount of protrusion of the balloon membrane material into the gap of the stent (amount of the balloon membrane material sandwiched in the gap of the stent). Is reduced, and the retention of the stent is reduced.

In view of the above problems, the present invention provides a stent delivery system capable of suppressing the occurrence of pinholes in the balloon on which the stent is placed, reducing the diameter of the profile, and improving the retention of the stent. It is an object of the present invention to provide a manufacturing method.

The method for manufacturing a stent delivery system according to the present invention is a method for manufacturing a stent delivery system including a stent and a balloon catheter including a balloon on which the stent is placed, wherein the folded balloon is contained in the stent. The placement step of arranging the stent in the cavity, the first diameter reduction step of applying pressure to the stent from the radial outside of the stent to reduce the diameter of the stent, and the pressurization of the inside of the balloon to the first pressure. A second diameter reduction step of reducing the diameter of the stent while applying pressure to the stent from the inside in the radial direction of the stent is provided, and the first pressure is the first pressure at which the stent starts expansion. Less than 2 pressures.

In the above-mentioned method for manufacturing a stent delivery system, at least a part of the balloon can be sandwiched in the gap between the stents by continuing to pressurize the inside of the balloon during the second diameter reduction step. .. Thereby, the method for manufacturing the stent delivery system described above can improve the retention of the stent. Further, in the above-mentioned method for manufacturing a stent delivery system, the inside of the balloon is maintained at a first pressure smaller than the second pressure at which the stent starts expanding until the outer diameter of the stent reaches the target outer diameter. Therefore, in the above-mentioned manufacturing method of the stent delivery system, it is possible to prevent stress from concentrating on a part of the balloon sandwiched in the gap portion of the stent during the second diameter reduction step. Thereby, the above-mentioned method for manufacturing the stent delivery system can suppress the occurrence of pinholes in the balloon. Further, in the above-mentioned manufacturing method of the stent delivery system, by setting the first pressure to be smaller than the second pressure, it is possible to suppress the expansion of the stent during the second diameter reduction step. Therefore, in the above-mentioned manufacturing method of the stent delivery system, the diameter of the profile can be reduced as compared with the case where the first pressure is set to be larger than the second pressure.

It is an overall schematic view of the stent delivery system which concerns on embodiment. It is a development view of the stent which concerns on embodiment. It is an enlarged sectional view of the broken line part 3A shown in FIG. It is a flowchart which shows the manufacturing method of the stent delivery system which concerns on embodiment. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment. It is a schematic cross-sectional view for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment, and is the figure which shows the part of the stent and the balloon enlarged. It is a schematic cross-sectional view for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment, and is the figure which shows the part of the stent and the balloon enlarged. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment. It is the schematic sectional drawing for demonstrating the manufacturing method of the stent delivery system which concerns on embodiment.

Hereinafter, embodiments of the present invention will be described with reference to the attached drawings. The following description does not limit the technical scope and meaning of terms described in the claims. In addition, the dimensional ratios in the drawings are exaggerated for convenience of explanation and may differ from the actual ratios. Further, the range "X to Y" shown in the present specification means "X or more and Y or less".

FIG. 1 is a diagram showing a stent delivery system 10 according to an embodiment, FIG. 2 is a diagram showing a stent 200 according to an embodiment, and FIG. 3 is an enlarged view of a part of the stent delivery system 10 according to the embodiment. It is a sectional view. 4 to 13 are views for explaining the manufacturing method of the stent delivery system 10 according to the embodiment. FIG. 4 is a flowchart showing each process of a method for manufacturing a stent delivery system, and FIGS. 5 to 13 are schematic cross-sectional views for explaining a method for manufacturing a stent-delivery system. 3 is an enlarged cross-sectional view taken along the axial direction of the broken line portion 3A shown in FIG. 1, and FIGS. 5 to 13 are views showing a simplified axial cross section along the arrows 5A-5A shown in FIG. Is.

In the description of the present specification, the distal end side of the stent delivery system 10 means the end side (lower side of FIG. 3) inserted into the blood vessel, and the hub 180 is arranged on the proximal end side of the stent delivery system 10. It means the end side (upper side in FIG. 3). The "tip" means the tip of the member, and the "tip" means the tip and a predetermined range from the tip to the base end side. The "base end" means the most base end of the member, and the "base end portion" means the base end and a predetermined range from the base end to the tip side. The "axial direction" means the extending direction of the shaft 110 (vertical direction in FIG. 3). The “circumferential direction” means the direction around the axis O of the shaft 110 (inner pipe 120) (direction indicated by arrows R1-R2 in FIG. 5).

In the description of the stent 200 according to the embodiment, the “diameter direction” means the direction (arrows A1-A2 direction in FIG. 5) approaching-distant from the axial center O of the shaft 110 (inner tube 120). The definitions of the tip end, the proximal end, the axial direction, and the circumferential direction of the stent 200 are the same as the definitions of the stent delivery system 10 described above. In the developed view of the stent 200 shown in FIG. 2, the axial direction of the stent 200 is indicated by arrows X1-X2, and the circumferential direction of the stent 200 is indicated by arrows Y1-Y2.

The method for manufacturing the stent delivery system according to the present embodiment (hereinafter, also simply referred to as “manufacturing method”) can be used for manufacturing the stent delivery system 10 shown in FIGS. 1 to 3. Hereinafter, the configuration of each part of the stent delivery system 10 will be described, and then the manufacturing method according to the present embodiment will be described.

<Stent delivery system>
As shown in FIGS. 1 and 3, the stent delivery system 10 has a balloon catheter 100 and a stent 200 placed on the balloon 150 of the balloon catheter 100.

The stent delivery system 10 is a medical device used for a procedure (for example, PCI) of expanding a stenosis formed in a living lumen such as a blood vessel. In a procedure using the stent delivery system 10, the operator inserts the stent 200 crimped into the balloon 150 into the living lumen together with the balloon 150 arranged at the tip of the shaft 110. The operator expands the balloon 150 on the inner peripheral side of the stenosis formed in the lumen of the living body, and expands the stent 200 together with the balloon 150. By placing the expanded stent 200 on the inner peripheral side of the stenosis, the operator can maintain the stenosis in an expanded state.

<Balloon catheter>
As shown in FIGS. 1 and 3, the balloon catheter 100 is arranged at a flexible long shaft 110, a balloon 150 arranged at the tip of the shaft 110, and a proximal end of the shaft 110. It has a hub 180 and a hub 180.

As shown in FIG. 3, the shaft 110 can be composed of an inner pipe 120 and an outer pipe 130. The inner tube 120 penetrates the lumen of the outer tube 130. A certain range on the tip side of the inner tube 120 projects toward the tip side of the outer tube 130. A guide wire lumen 123 through which the guide wire W shown in FIG. 1 can be inserted is formed in the inner pipe 120. On the inner peripheral side of the outer pipe 130, a lumen 133 for a pressure medium partitioned between the outer pipe 130 and the inner pipe 120 is formed.

As shown in FIG. 3, a tip opening 122a is formed at the tip of the inner tube 120. Further, a tip member (tip tip) 160 having flexibility is arranged on the tip side of the inner tube 120. The tip member 160 has a tip opening 161, a hollow cavity 162, and a proximal opening 163. The guide wire lumen 123 of the inner tube 120 communicates with the lumen 162 of the tip member 160.

The tip member 160 can be configured to have, for example, a tapered cross section curved toward the tip side. The tip member 160 can be configured to have more flexible physical properties than, for example, the shaft 110 (inner tube 120 and outer tube 130). Examples of the constituent material of the tip member 160 include polyolefin (for example, polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or a mixture of two or more thereof) and polychloride. Polymer materials such as vinyl, polyamide, polyamide elastomer, polyurethane, polyurethane elastomer, polyimide, and fluororesin, or mixtures thereof can be used.

As shown in FIG. 1, the shaft 110 is formed with a guide wire port 113 communicating with the guide wire lumen 123.

The stent delivery system 10 according to the present embodiment is configured as a so-called "rapid exchange type" catheter in which a guide wire port 113 capable of leading the guide wire W to be led out is formed in an intermediate portion of the shaft 110 in the axial direction. ing. The stent delivery system 10 may be configured as an "over-the-wire type" catheter in which the guide wire lumen 123 is formed over the entire length of the shaft 110 and the guide wire W is led out from the base end of the hub 180.

As shown in FIG. 3, contrast markers 171 and 172 can be arranged in the inner tube 120 to indicate the positions of both ends in the axial direction of the stent 200. The contrast marker 171 can be arranged on the axially distal end side of the shaft 110 with respect to the distal end of the stent 200. Further, the contrast marker 172 can be arranged on the axially proximal end side of the shaft 110 with respect to the proximal end of the stent 200. In this way, the contrast markers 171 and 172 can be arranged at positions that do not overlap the stent 200 in the axial direction of the shaft 110. As the constituent materials of the contrast markers 171 and 172, for example, known metal materials can be used.

As shown in FIG. 3, a tip opening 132a is formed at the tip of the outer tube 130. The tip opening 132a of the outer tube 130 communicates with the space portion 155 of the balloon 150. The surgeon operates a fluid supply device (not shown) connected to the hub 180 to supply the pressure medium into the space 155 of the balloon 150 via the lumen 133 for the pressure medium, whereby the balloon 150 Can be extended. Further, the operator can operate the fluid supply device to discharge the fluid from the space 155 of the balloon 150, whereby the balloon 150 can be contracted. The type of the pressurizing medium is not particularly limited, and for example, a gas such as air or a liquid such as physiological saline can be used.

Examples of the constituent materials of the inner tube 120 include polyolefins such as polyethylene, polypropylene, ethylene-propylene copolymer, and ethylene-vinyl acetate copolymer, thermoplastic resins such as soft polyvinyl chloride, silicone rubber, and latex rubber. Various rubbers, polyurethane elastomers, polyamide elastomers, polyester elastomers, various elastomers such as styrene-based thermoplastic elastomers, and crystalline plastics such as polyamide, crystalline polyethylene, and crystalline polypropylene can be used.

As the constituent material of the outer pipe 130, for example, the same material as those exemplified as the constituent material of the inner pipe 120 can be used.

A coat layer made of a swellable polymer may be provided on the outer surface of the shaft 110 (the outer surface of the outer tube 130). The swellable polymer is not particularly limited as long as it exhibits swellability when in contact with a body fluid or an aqueous solvent. For example, cellulose-based polymer substances, polyethylene oxide-based polymer substances, maleic anhydride-based polymer substances (for example, maleic anhydride copolymers such as methyl vinyl ether-maleic anhydride copolymer), acrylamide-based polymer substances. (For example, a block copolymer of polyacrylamide, glycidyl methacrylate-dimethylacrylamide), water-soluble nylon, polyvinyl alcohol, polyvinylpyrrolidone and the like can be mentioned. The swellable polymer may be used alone or in combination of two or more. The coat layer can be provided, for example, on the proximal end side of the balloon 150.

As shown in FIG. 3, the balloon 150 has a body portion 151 that can be expanded substantially linearly, and a tip side inclination that is arranged on the tip end side of the body portion 151 and is inclined toward the tip end side toward the axial center O side of the shaft 110. The tip region 152 having the tip side fixing portion 152b fixed to the shaft 110 arranged on the tip side of the portion 152a and the tip side inclined portion 152a, and the shaft 110 arranged on the base end side of the body portion 151 and facing the base end side. It has a proximal end side inclined portion 153a inclined to the axial center O side and a proximal end region 153 having a proximal end side fixed portion 153b arranged on the proximal end side of the proximal end side inclined portion 153a and fixed to the shaft 110. are doing.

The stent 200 is located on the outer surface of the body 151 of the balloon 150. Although FIG. 3 shows the balloon 150 in an expanded state for convenience of illustration, the stent 200 has a body of the balloon 150 in an unexpanded state (wrapped state) in which the balloon 150 is folded. It is crimped to the outer surface of 151.

The tip-side fixing portion 152b of the balloon 150 is fixed to the tip portion 122 of the inner tube 120 constituting the shaft 110. The base end side fixing portion 153b of the balloon 150 is fixed to the tip end portion 132 of the outer tube 130 constituting the shaft 110. A space portion 155 through which the pressurizing medium can flow in is formed on the inner peripheral side of the balloon 150. The balloon 150 is made of a flexible film material 150a that can be expanded and contracted.

As the constituent material of the film material 150a of the balloon 150, for example, an organic polymer material can be used. Specifically, polyolefins (eg, polyethylene, polypropylene, polybutene, ethylene-propylene copolymers, ethylene-vinyl acetate copolymers, ionomers, or mixtures of two or more of these), polyvinyl chloride, polyamides, polyamide elastomers, etc. , Polyolefins, polyurethane elastomers, polyimides, fluororesins and the like, or mixtures thereof, or multilayer tubes of the above two or more kinds of polymer materials can be used.

The thickness of the film material 150a can be formed, for example, from 1 μm to 100 μm, preferably from 15 μm to 40 μm. By forming the thickness of the membrane material 150a to such a size, when the diameter reduction step (S3) and the pressurization step (S4) described later are performed, at least a part of the membrane material 150a of the balloon 150 is stented 200. It becomes possible to suitably sandwich it in the second gap g2 of the above (see FIG. 10).

<Stent>
The stent 200 is a so-called balloon expansion type stent that expands with plastic deformation by the expanding force of the balloon 150.

As shown in FIG. 2, the stent 200 has a plurality of annular portions extending in a wavy shape in the circumferential direction indicated by arrows Y1-Y2 and arranged at predetermined intervals in the axial direction indicated by arrows X1-X2. It has a 211 and a plurality of link portions 212 that connect adjacent annular portions 211 in the axial direction. Note that FIG. 2 shows a developed view of the stent 200.

The stent 200 is configured to have a tubular shape (cylindrical shape). A lumen 230 into which the balloon 150 can be inserted is formed on the inner peripheral side of the stent 200 (see FIG. 5).

The annular portion 211 of the stent 200 comprises a plurality of linear elements 211a, 211b, 211c, 211d extending along the axial direction of the stent 200 and arranged at different positions in the circumferential direction, and a curved portion connecting the linear elements. Have. The annular portion 211 includes a first linear element 211a, a second linear element 211b, a third linear element 211c, and a fourth linear element 211d as one unit along the circumferential direction of the stent 200. Includes a periodic structure. In FIG. 2, for convenience of illustration, only some linear elements are coded. Further, the linear element includes not only a form extending substantially straight along the axial direction but also a form extending along the axial direction while partially or wholly meandering.

The stent 200 has a gap g between the linear elements of the stent 200. The gap g includes a linear element 211a (hereinafter, referred to as “first linear element 211a”) and a linear element 211b (hereinafter, “second linear element 211b”) adjacent to each other in the circumferential direction of the stent 200. The first gap g1 formed between the stent 200 and the linear element 211c (hereinafter referred to as “third linear element 211c”) and the linear element 211d (hereinafter referred to as “third linear element 211c”) adjacent to the stent 200 in the circumferential direction. Hereinafter, it has at least a second gap g2 formed between the "fourth linear element 211d").

The second gap g2 is formed at a position different from that of the first gap g1 in the circumferential direction of the stent 200. Further, the second gap g2 has a longer length along the circumferential direction of the stent 200 than the first gap g1.

The length L1 along the circumferential direction of the first gap g1 and the length L2 along the circumferential direction of the second gap g2 shall be compared by the maximum lengths of the respective gaps g1 and g2 in the circumferential direction of the stent 200. Can be done. The lengths L1 and L2 are the lengths before the stent 200 is crimped by the balloon 150.

It is preferable that the film material 150a of the balloon 150 is not sandwiched in the first gap g1 in a state where the stent 200 is crimped on the balloon 150. Further, it is preferable that at least a part of the film material 150a of the balloon 150 is sandwiched in the second gap g2 with the stent 200 crimped on the balloon 150. This is due to the following reasons.

The length L1 of the first gap g1 of the stent 200 along the circumferential direction of the stent 200 is shorter than the length L2 of the second gap g2 along the circumferential direction of the stent 200. Therefore, the amount of the film material 150a of the balloon 150 sandwiched between the gaps g is smaller in the first gap g1 than in the second gap g2. As shown in FIG. 9, as the diameter of the stent 200 is reduced, the first linear element 211a and the second linear element 211b come into contact with each other via the membrane material 150a of the balloon 150, and the second of the stent 200 The film material 150a of the balloon 150 sandwiched in the gap g1 of 1 receives stress from the stent 200. The film material 150a of the balloon 150 sandwiched in the first gap g1 is in a state of being pinched by the first linear element 211a and the second linear element 211b, and extends radially outward. Can't. Therefore, at the contact point t between the inner surface side of the linear element of the stent 200 and the outer surface side of the film material 150a of the balloon 150, the stress for extending the film material 150a is the stress of the balloon 150 sandwiched in the gap g2. It cannot be dispersed in the film material 150a and concentrates on the contact point t. As a result, the balloon 150 is prone to pinholes. Therefore, it is preferable that the membrane material 150a of the balloon 150 is not sandwiched in the first gap g1 with the stent 200 crimped on the balloon 150. On the other hand, the length L2 of the second gap g2 of the stent 200 along the circumferential direction of the stent 200 is longer than the length L1 of the first gap g1 along the circumferential direction of the stent 200. Therefore, as shown in FIG. 10, when the diameter of the stent 200 is reduced while pressurizing the inside of the balloon 150 to the first pressure, at least one of the membrane materials 150a of the balloon 150 located near the second gap g2. The portion is easily sandwiched in the second gap portion g2. This enhances the retention of the stent 200. Therefore, it is preferable that at least a part of the membrane material 150a of the balloon 150 is sandwiched in the second gap g2 with the stent 200 crimped on the balloon 150. At this time, the amount of the film material 150a of the balloon 150 sandwiched between the gaps g is larger in the second gap g2 than in the first gap g1. Therefore, air, which is a pressurizing medium, can enter between the membrane materials 150a of the balloon 150 sandwiched in the second gap g2, and therefore, by applying pressure, the third linear element 211c It is avoided that the fourth linear element 211d and the fourth linear element 211d come into contact with each other via the film material 150a of the balloon 150. As a result, the film material 150a of the balloon 150 sandwiched in the second gap g2 can extend radially outward in the second gap g2. As a result, it is possible to prevent the stress for extending the membrane material 150a of the balloon 150 from being concentrated on the contact point t between the inner surface side of the linear element of the stent 200 and the outer surface side of the membrane material 150a of the balloon 150. The balloon 150 located in the vicinity of the gap g2 is less likely to cause a pinhole.

The state in which the film material 150a constituting the balloon 150 is not sandwiched in the first gap g1 and is sandwiched in the second gap g2 is a state in which the inside of the balloon 150 is sandwiched in the diameter reduction step of the stent 200. This can be achieved by setting the pressurizing pressure to be smaller than the pressure at which the stent 200 starts expanding (stent expansion starting pressure), and by continuing the pressurization until the outer diameter of the stent 200 reaches the target outer diameter. When the pressurizing pressure inside the balloon 150 is larger than the stent expansion starting pressure, the gap g of the stent 200 is expanded, so that it is difficult to reduce the diameter of the stent 200 to the target outer diameter while continuing the pressurization. Further, since the first gap g1 having a short length L1 along the circumferential direction of the stent 200 is also expanded, it seems that the membrane material 150a of the balloon 150 is sandwiched and pinched by the first gap g1. The balloon 150 is in such a state that pinholes are likely to occur. In the diameter reduction step of the stent 200, the pressure inside the balloon 150 is set to be smaller than the stent expansion start pressure, and the pressure is continued until the outer diameter of the stent 200 reaches the target outer diameter. While suppressing the film material 150a constituting the above from being sandwiched in the first gap portion g1, it is possible to bring the film material 150a into a state of being sandwiched in the second gap portion g2. As a result, the balloon 150 can sandwich at least a part of the membrane material 150a of the balloon 150 into the gap g of the stent 200 without generating pinholes until the diameter reduction step of the stent 200 is completed.

The length L1 along the circumferential direction of the first gap portion g1 can be, for example, 100 μm to 300 μm. Further, the length L2 along the circumferential direction of the second gap portion g2 can be, for example, 500 μm to 1000 μm.

The structure of the stent 200 (shape of linear element, shape of gap, etc.) is not limited to that shown in FIG. For example, as the stent 200, one having a tubular peripheral wall formed of a mesh in which a large number of gaps are formed can also be used.

As the constituent material of the stent 200, for example, a metal having biocompatibility, a biodegradable polymer having bioabsorbability, or the like can be used. In addition, one stent 200 may be provided with a portion formed of a biocompatible metal and a portion formed of a biodegradable polymer having bioabsorbability.

Examples of biocompatible metals include iron-based alloys such as stainless steel, tantalum (tantal alloy), platinum (platinum alloy), gold (gold alloy), cobalt-based alloy, cobalt-chromium alloy, titanium alloy, and niobium alloy. Etc. can be used.

Examples of biodegradable polymers include polylactic acid, polyglycolic acid, copolymers of lactic acid and glycolic acid, polycaprolactone, polyhydroxybutyric acid, polyhydroxybutyrate valeric acid, polyappleic acid, poly-α-amino acid, and poly. A single polymer constituting at least one polymer selected from the group consisting of orthoester, cellulose, collagen, laminin, heparan sulfate, fibronectin, vitronectin, chondroitin sulfate, hyaluronic acid, trabecular acid, and trabecular acid derivative. It is preferable that the polymer is a copolymer in which the polymer is arbitrarily copolymerized, or a mixture of the polymer and the copolymer.

As shown in FIG. 3, a drug coating layer 220 containing a drug can be provided on the outer surface of the stent 200. The drug coat layer 220 may be formed on the entire outer surface of the stent 200, or may be formed only on a part of the outer surface of the stent 200.

The drug contained in the drug coat layer 220 is not particularly limited, and for example, an anticancer drug, an immunosuppressant, an antibiotic, an antirheumatic drug, an antithrombotic drug, an antihyperlipidemic drug, an ACE inhibitor, and calcium. Antagonists, integrin inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotinoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, vascular smooth muscle growth inhibitors, Anti-inflammatory agents, biological materials, interferons, NO production promoting substances and the like can be used.

<Manufacturing method of stent delivery system>
Next, a method of manufacturing the stent delivery system 10 according to the present embodiment will be described with reference to FIGS. 4 to 13. Here, each procedure up to crimping the stent 200 into the balloon 150 will be described.

Each of the explanatory cross-sectional views shown in FIGS. 5 to 13 schematically shows the balloon 150, the stent 200, and a part (crimp head) 300 of the manufacturing apparatus used in the manufacturing method.

As shown in FIG. 4, the manufacturing method is roughly described as an arrangement step (S1), a first diameter reduction step (S2), a second diameter reduction step (S3), a continuation step (S4), and a release step. (S5) and. Hereinafter, each step of the manufacturing method will be described.

The operator prepares the balloon catheter 100, the stent 200, and the crimp device when starting the manufacture of the stent delivery system 10. The balloon catheter 100 is prepared with the balloon 150 in a folded state. As the stent 200, a stent 200 that is not arranged on the balloon 150 and is in a state before the diameter is reduced (the initial outer diameter before the diameter is reduced is, for example, 1 mm to 6 mm) is prepared. Further, a drug coat layer 220 can be provided on the outer surface of the stent 200. As the crimping device, a known one including a crimp head 300 for crimping the stent 200 to the balloon 150 can be prepared.

The worker first carries out the placement step (S1). In the placement step (S1), the operator sets the stent 200 on the crimp head 300 of the crimp device. The operator also places the balloon 150 in the lumen 230 of the stent 200, as shown in FIG. The stent 200 is placed on the body 151 of the balloon 150.

Next, the operator carries out the first diameter reduction step (S2). In the first diameter reduction step (S2), the operator applies pressure to the stent 200 from the radial outside of the stent 200 to reduce the diameter of the stent 200 to a predetermined outer diameter. FIG. 6 shows a state when the first diameter reduction step (S2) is started. The operator applies pressure to the stent 200 from the radially outer side by reducing the diameter of the crimp head 300 arranged on the radial outer side of the stent 200 in the radial direction. In the first diameter reduction step (S2), the balloon 150 is not pressurized. Therefore, in the first diameter reduction step (S2), the balloon 150 is not sandwiched in the gap g of the stent 200.

Next, the worker carries out the second diameter reduction step (S3). In the second diameter reduction step (S3), the operator pressurizes the inside of the balloon 150 (space portion 155) to a predetermined first pressure, and applies pressure to the stent 200 from the radial inside of the stent 200. .. The pressure applied to the inside of the balloon 150 can be performed by supplying a fluid such as air into the balloon 150. FIG. 7 shows a state when the second diameter reduction step (S3) is started. The pressure applied to the inside of the balloon 150 may be applied at the same time as the diameter reduction in the second diameter reduction step (S3), or may be performed before the start of the second diameter reduction step (S3).

The second diameter reduction step (S3) can be started after the stent 200 has been reduced in diameter to a predetermined outer diameter by the first diameter reduction step (S2). When the second diameter reduction step (S3) is started after the stent 200 has been reduced in diameter to a predetermined outer diameter, for example, the outer diameter of the stent 200 has reached 0.8 mm to 4 mm, preferably 0.9 mm to 1.7 mm. At that time, the pressurization of the balloon 150 can be started. The operator may start the second diameter reduction step (S3) without performing the first diameter reduction step (S2).

In the second diameter reduction step (S3), the operator makes the first pressure for pressurizing the inside of the balloon 150 smaller than the predetermined second pressure. The "second pressure" is the pressure at which the stent begins to expand in the circumferential direction (stent expansion starting pressure). In addition, "less than the second pressure" means "less than the second pressure".

The second pressure is determined based on the shape and structure of the stent 200. The second pressure is, for example, 0.3 MPa to 1 MPa. The first pressure can be set, for example, 0.1 MPa to 0.3 MPa when the second pressure is 0.4 MPa to 0.5 MPa. However, the first pressure is not particularly limited as long as it is smaller than the second pressure.

While the operator is performing the second diameter reduction step (S3), the operator sets the pressure inside the balloon 150 to a first pressure smaller than the second pressure in the second diameter reduction step (S3). It is possible to prevent the stent 200 from expanding.

FIG. 8 shows a state of the second diameter reduction step (S3) in which the stent 200 is reduced in diameter while applying pressure to the inside of the balloon 150. In the manufacturing method according to the present embodiment, the operator continues the second diameter reduction step (S3) until the outer diameter of the stent 200 reaches the target outer diameter. That is, the operator continues to pressurize the balloon 150 until the outer diameter of the stent 200 reaches the target outer diameter.

FIG. 9 shows the state of the film material 150a of the balloon 150 located in the vicinity of the first gap portion g1 when the second diameter reduction step (S3) is being carried out.

The circumferential length L1 of the stent 200 of the first gap g1 of the stent 200 is shorter than the circumferential length L2 of the stent 200 of the second gap g2 (see FIG. 2). Therefore, as shown in FIG. 9, when the pressure inside the balloon 150 is pressurized to the first pressure, the film material 150a of the balloon 150 located in the vicinity of the first gap g1 becomes the first gap g1. It is hard to be caught inside. Further, the first pressure for pressurizing the inside of the balloon 150 is set to be smaller than the second pressure which is the stent expansion starting pressure. Thereby, during the second diameter reduction step (S3), it is possible to prevent the stent 200 from expanding and the membrane material 150a of the balloon 150 being sandwiched in the first gap g1. Therefore, the operator can suppress the occurrence of pinholes in the film material 150a of the balloon 150 located near the first gap g1 in which the length L1 in the circumferential direction of the stent 200 is short.

FIG. 10 shows the state of the film material 150a of the balloon 150 located near the second gap g2 when the second diameter reduction step (S3) is being carried out.

The circumferential length L2 of the stent 200 of the second gap g2 of the stent 200 is longer than the circumferential length L1 of the stent 200 of the first gap g1 (see FIG. 2). Therefore, as shown in FIG. 10, when the pressure inside the balloon 150 is pressurized to the first pressure, at least a part of the film material 150a of the balloon 150 located near the second gap g2 is second. It is easily sandwiched in the gap g2. Then, the pressurization to the inside of the balloon 150 continues until the outer diameter of the stent 200 reaches the target outer diameter. As a result, while the second diameter reduction step (S3) is being carried out, the film material 150a of the balloon 150 between the third linear element 211c and the fourth linear element 211d forming the second gap g2. It is possible to avoid contact through. Therefore, the operator can suppress the occurrence of pinholes in the film material 150a of the balloon 150 located near the second gap g2 in which the length L2 in the circumferential direction of the stent 200 is formed to be long. The portion of the membrane material 150a of the balloon 150 sandwiched in the second gap g2 maintains the state of being sandwiched in the second gap g2 even after the crimp of the stent 200 with respect to the balloon 150 is completed. .. The operator can increase the retention of the stent 200 with respect to the balloon 150 by sandwiching at least a part of the film material 150a of the balloon 150 into the second gap g2.

As described above, according to the manufacturing method according to the present embodiment, the stent delivery system 10 suppresses the film material 150a of the balloon 150 from being sandwiched in the first gap g1 while suppressing the film material 150a of the balloon 150. At least a part of 150a is sandwiched in the second gap g2. As a result, the stent delivery system 10 can increase the retention of the stent 200 while suppressing the occurrence of pinholes.

FIG. 11 shows a state when the outer diameter of the stent 200 reaches the target outer diameter. The target outer diameter can be set to, for example, 0.4 mm to 1.5 mm. At least a part of the film material 150a of the balloon 150 is maintained in a state of being sandwiched in the second gap g2 of the stent 200 after the completion of the second diameter reduction step (S3).

The first pressure for pressurizing the inside of the balloon 150 in the second diameter reduction step (S3) is set to be smaller than the second pressure which is the stent expansion starting pressure. By setting the first pressure to be smaller than the second pressure, it is possible to suppress the expansion of the stent 200 during the second diameter reduction step (S3). Therefore, the stent delivery system 10 can reduce the diameter of the profile as compared with the case where the first pressure is set to be larger than the second pressure.

The first pressure for pressurizing the inside of the balloon 150 in the second diameter reduction step (S3) can be maintained constant until the outer diameter of the stent 200 reaches the target outer diameter. By maintaining the first pressure constant, while suppressing the film material 150a of the balloon 150 from being pinched in the first gap g1 during the second diameter reduction step (S3), the first It is possible to stably maintain a state in which at least a part of the film material 150a of the balloon 150 is sandwiched in the gap g2 of 2. The first pressure may be increased or decreased within a range of a pressure smaller than the second pressure during the pressurizing step.

By carrying out the second diameter reduction step (S3), the operator starts the continuation step (S4) after the outer diameter of the stent 200 reaches the target outer diameter.

In the continuation step (S4), the operator continues to apply the pressure from the radial outside to the stent 200 and the pressure from the radial inside to the stent 200 for a predetermined time. That is, after the outer diameter of the stent 200 reaches the target outer diameter, the operator does not immediately release the pressurization inside the balloon 150 and the pressure applied to the stent 200 from the crimp head 300, but at a predetermined time. The pressure applied from the balloon 150 to the stent 200 and the pressure applied from the crimp head 300 to the stent 200 are continued. The operator can obtain the following effects by carrying out the continuation step (S5).

Immediately after the outer diameter of the stent 200 reaches the target outer diameter, when the pressure applied from the balloon 150 to the stent 200 and the pressure applied from the crimp head 300 to the stent 200 are released, springback occurs in the stent 200. The diameter of the stent 200 expands when springback occurs. The operator performs the second diameter reduction step (S3) and then the continuation step (S4) to release the pressure applied to the stent 200 from the balloon 150 and the crimp head 300, and then the spring generated in the stent 200. The degree of backing can be reduced.

In the continuation step (S4), for example, the inside of the balloon 150 can be pressurized with the first pressure. The pressure applied from the crimp head 300 to the stent 200 can be set to, for example, 30N to 500N. Further, the continuation step (S4) can be continued for, for example, 15 seconds to 20 seconds.

Next, the worker carries out the release step (S5).

In the release step (S5), the operator releases the application of the pressure from the balloon 150 to the stent 200 from the radial inside and the pressure applied from the crimp head 300 to the stent 200 from the radial outside. Specifically, the operator releases the pressure inside the balloon 150 and spreads the crimp head 300 outward in the radial direction of the stent 200. FIG. 12 shows the state of the release step (S5).

By the above work procedure, the stent delivery system 10 in which the stent 200 is crimped to the balloon 150 of the balloon catheter 100 can be manufactured.

In the manufacturing method according to the present embodiment, the pressure applied to the stent 200 and the balloon 150 in the second diameter reduction step (S3) is adjusted to suppress the occurrence of pinholes, improve retention, and reduce the profile. We are trying to increase the diameter. Therefore, it is not necessary to heat or cool the balloon 150 or the stent 200 during each manufacturing process.

As described above, the present embodiment provides a method for manufacturing a stent delivery system 10 having a stent 200 and a balloon catheter 100 including a balloon 150 on which the stent 200 is arranged. The manufacturing method comprises a placement step (S1) in which the folded balloon 150 is placed in the lumen 230 of the stent 200, and a pressure is applied to the stent 200 from the radial outside of the stent 200 to reduce the diameter of the stent 200. In the first diameter reduction step (S2), the inside of the balloon 150 is pressurized to the first pressure, and the stent 200 is reduced in diameter while applying pressure to the stent 200 from the radial inside of the stent 200. It has a diameter step (S3). The first pressure in the second diameter reduction step (S3) is smaller than the second pressure at which the stent 200 begins to expand.

In the method for manufacturing the stent delivery system 10 described above, at least a part of the balloon 150 is made into the stent 200 by continuing to pressurize the inside of the balloon during the second diameter reduction step (S3). It can be sandwiched in the gap g2 (between the third linear element 211c and the fourth linear element 211d) of 2. Thereby, the above-mentioned manufacturing method of the stent delivery system 10 can improve the retention of the stent 200. Further, in the above-mentioned manufacturing method of the stent delivery system 10, the inside of the balloon 150 is maintained at a first pressure smaller than the second pressure at which the stent 200 starts expanding until the outer diameter of the stent 200 reaches the target outer diameter. Will be done. Therefore, in the above-mentioned manufacturing method of the stent delivery system 10, the first gap g1 (first linear element 211a and second wire) of the stent 200 is performed while the second diameter reduction step (S3) is being carried out. The balloon 150 is sandwiched between the shape element 211b), and stress can be prevented from concentrating on a part of the balloon 150. Thereby, the above-mentioned manufacturing method of the stent delivery system 10 can suppress the occurrence of pinholes in the balloon 150. Further, in the above-mentioned manufacturing method of the stent delivery system 10, the first pressure is set to be smaller than the second pressure so that the stent 200 expands during the second diameter reduction step (S3). Can be suppressed. Therefore, in the above-mentioned manufacturing method of the stent delivery system 10, the diameter of the profile can be reduced as compared with the case where the first pressure is set to be larger than the second pressure.

Further, the stent 200 is formed at different positions in the circumferential direction of the stent 200 from the first gap g1 and the first gap g1 and has a length along the circumferential direction of the stent 200 with respect to the first gap g1. A second gap g2 having a long length is provided. In the manufacturing method according to the present embodiment, in the second diameter reduction step (S3), the film material 150a constituting the balloon 150 is suppressed from being sandwiched in the first gap g1 and the second gap g2 is suppressed. At least a part of the film material 150a of the balloon 150 is sandwiched therein. Therefore, it is possible to suppress the occurrence of pinholes caused by the film material 150a of the balloon 150 being sandwiched in the first gap g1. Further, the retention of the stent 200 with respect to the balloon 150 can be improved by sandwiching at least a part of the film material 150a of the balloon 150 in the second gap g2.

Further, in the above manufacturing method, the first pressure is maintained constant until the stent 200 reaches the target outer diameter. Therefore, while suppressing the film material 150a of the balloon 150 from being sandwiched in the first gap g1 while the second diameter reduction step (S3) is being performed, the balloon 150 is contained in the second gap g2. The state in which the film material 150a is sandwiched can be stably maintained.

Further, the above manufacturing method is a continuous step in which, after the stent 200 reaches the target outer diameter, the pressure is applied to the stent 200 from the radial outside and the pressure is applied to the stent 200 from the radial inside for a predetermined time. It has (S4). Therefore, the operator can prevent the stent 200 from springing back and expanding the diameter of the stent 200 when the pressure applied to the stent 200 is released after the second diameter reduction step (S3) is completed. ..

The stent 200 is a drug-eluting stent provided with a drug-coated layer 220. In the manufacturing method according to the present embodiment, the pressure applied to the stent 200 and the balloon 150 in the second diameter reduction step (S3) is adjusted to suppress the occurrence of pinholes, improve retention, and reduce the diameter of the profile. I am trying to. Therefore, it is not necessary to heat or cool the balloon 150 or the stent 200 during each manufacturing process. Therefore, the drug-coated layer 220 provided on the outer surface of the stent 200 before the start of the manufacturing operation is not affected by the temperature change throughout each step of the manufacturing operation. Therefore, the drug-coated layer 220 provided on the stent 200 can appropriately maintain the efficacy of the drug contained in the drug-coated layer 220.

(Example)
Hereinafter, examples of the present invention will be described. In the description of the embodiment, a part of the drawings shown in the above-described embodiment will be cited and described together with the member number. However, the present invention is not limited to the contents shown in the drawings and the contents of the examples described below.

Tables 1 and 2 show the conditions and test results adopted in the manufacturing method according to the examples. In addition, Tables 1 and 2 also show the conditions and test results adopted in the manufacturing methods according to Reference Examples 1 to 6 used for comparison with the implementation results of Examples.

The conditions shown in Tables 1 and 2 are as follows.
1. 1. The “pressurization start diameter” is the outer diameter of the stent 200 when the second diameter reduction step (S3) is started.
2. “Presence / absence of pressurization to the target outer diameter” indicates whether or not the second diameter reduction step (S3) was continued until the second diameter reduction step (S3) was completed, that is, until the stent 200 reached the target outer diameter. Is shown.
3. 3. The “target outer diameter” is a target value of the outer diameter of the stent 200 after the second diameter reduction step (S3).
4. The "pressurizing pressure" is the pressure (first pressure) for pressurizing the inside of the balloon 150 in the second diameter reduction step (S3). The second pressure (stent expansion starting pressure) of the stent 200 used in the examples and each reference example is 0.5 MPa.
5. "Retention" is the holding power of the stent 200 in a crimped state on the balloon 150. The measured value of retention is the tensile force when the stent 200 is pulled off from the balloon 150 when the stent 200 is pulled axially with respect to the balloon 150 (Initial peak displacement force described in ASTM F2394-07 (Reapprpved 2017)). Is. The retention measurement values under each condition shown in Table 2 are the overall average values of the measurement values measured for a plurality of samples.
6. “Presence / absence of pinhole” is whether or not a pinhole is generated in the balloon 150 when the outer diameter of the stent 200 reaches the target outer diameter.
7. A "profile" is the stent outer diameter of a stent 200 crimped into a balloon 150. The profile is an average value of each numerical value obtained by measuring the outer diameter of the tip of the stent 200, the outer diameter of the substantially central position of the stent 200 in the axial direction, and the outer diameter of the base end of the stent 200. The measured values of the profile under each condition shown in Table 2 are the overall average values of the measured values measured for a plurality of samples.

As shown in Tables 1 and 2, in the manufacturing method according to the examples, (i) the second diameter reduction step (S3) is carried out until the stent 200 reaches the target outer diameter, and (ii) the second diameter reduction is performed. The pressure inside the balloon 150 during the step (S3) was set to less than the second pressure (0.5 MPa). In the manufacturing method according to the examples, pinholes did not occur in the balloon 150 even though the target outer diameter of the stent 200 was the smallest as compared with each reference example. Further, in the stent delivery system 10 manufactured by the manufacturing method according to the example, the retention of the stent 200 was the largest as compared with each reference example. Further, the stent delivery system 10 manufactured by the manufacturing method according to the example had the smallest profile as compared with each reference example. As described above, it was confirmed that the manufacturing method according to the example can manufacture the stent delivery system 10 in which the occurrence of pinholes is suppressed, the retention is improved, and the diameter of the profile is reduced. Comparing Reference Examples 1 and 2, in Reference Example 2 in which the target outer diameter was reduced, the profile could be reduced, but the occurrence rate of pinholes in the balloon was high. Comparing Reference Examples 3 and 4, in Reference Example 4 in which the pressurizing pressure (first pressure) was lowered to be less than the stent expansion pressure (second pressure), the profile could be reduced, but the retention of the stent was high. It has decreased. Comparing Reference Examples 5 and 6, in Reference Example 6 in which the pressurization at the first pressure was continued up to the target outer diameter, the profile was small and the retention of the stent was also improved.

Although the method for manufacturing the stent delivery system according to the present invention has been described through the embodiments and examples, the present invention is not limited to the contents described in the specification, and is appropriately modified based on the description of the claims. It is possible to do.

The method for manufacturing a stent delivery system according to the present invention includes at least an arrangement step (S1), a first diameter reduction step (S2), and a second diameter reduction step (S3), and has a second diameter reduction step (S3). As long as S3) includes the content that the stent continues until the target outer diameter is reached, it can be changed as appropriate. The additional steps and operations described in the specification can be omitted as appropriate, and the additional steps and operations not described in the specification can be added as appropriate. For example, before starting the placement step (S1) or after completing the release step (S5), steps such as work for facilitating the crimping work of the stent on the balloon and surface treatment may be performed.

Further, the structure, shape, material, etc. of each part of the stent delivery system manufactured by the method for manufacturing the stent delivery system according to the present invention are not limited to the contents described in the specification.

10 Stent delivery system,
100 balloon catheter,
110 shaft,
120 inner tube,
130 outer pipe,
150 balloons,
150a Membrane material,
151 Balloon body,
200 stents,
211 Ring Road,
211a First linear element (linear element),
211b Second linear element (linear element),
211c Third linear element (linear element),
211d Fourth linear element (linear element),
212 link part,
220 drug coat layer,
230 Stent lumen,
300 crimp head,
O Shaft axis,
g Gap,
g1 first gap,
g2 Second gap.

Claims (5)

A method of manufacturing a stent delivery system comprising a stent and a balloon catheter comprising a balloon on which the stent is placed.
A placement step of placing the folded balloon in the lumen of the stent, and
A first diameter reduction step of applying pressure to the stent from the outside in the radial direction of the stent to reduce the diameter of the stent.
A second diameter reduction step of pressurizing the inside of the balloon to a first pressure and reducing the diameter of the stent to the target outer diameter while applying pressure to the stent from the radial inside of the stent. Have and
A method of manufacturing a stent delivery system, wherein the first pressure is less than the second pressure at which the stent begins to expand. The stent is formed at a position different in the circumferential direction of the stent from the first gap portion and the first gap portion, and has a longer length along the circumferential direction of the stent than the first gap portion. With a second gap,
The second diameter reduction step is claimed to sandwich at least a part of the film material in the second gap while suppressing the film material constituting the balloon from being sandwiched in the first gap. The method for manufacturing a stent delivery system according to 1. The method for manufacturing a stent delivery system according to claim 1 or 2, wherein the first pressure is kept constant until the stent reaches the target outer diameter. The claim comprises a continuous step of applying a pressure from the radial outer side to the stent and applying the pressure from the radial inner diameter to the stent for a predetermined time after the stent reaches the target outer diameter. The method for manufacturing a stent delivery system according to any one of 1 to 3. The method for manufacturing a stent delivery system according to any one of claims 1 to 4, wherein the stent is a drug-eluting stent provided with a drug-coated layer.