In-vivo indwelling tool and placement system for in-vivo indwelling tool

Abstract

Provided is an in-vivo indwelling tool (1) comprising a coil (10) which has a lumen (11) and a stretch resistance member (20) which is disposed in the lumen (11), which has a longitudinal axis direction, and a surface of which is provided with a drug (60), wherein the shape of the stretch resistance member (20) in a first cross-section, which is at a first position (21) in the longitudinal axis direction and perpendicular to the longitudinal axis direction, and the shape of the stretch resistance member (20) in a second cross-section, which is at a second position (22) in the longitudinal axis direction and perpendicular to the longitudinal axis direction, differ from each other.

Description

Intra-vivo implantable devices and implantation systems for intra-vivo implantable devices

[0001] This disclosure relates to an in vivo implantable device for forming an embolism in a blood vessel in a vascular diseased area, and to an implantation system for the in vivo implantable device.

[0002] Endovascular treatment is one of the treatment methods for vascular lesions such as head and neck aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal artery aneurysms, and abdominal aneurysms. In endovascular treatment, embolization is used to prevent rupture of aneurysms, for example, by implanting an in vivo device containing coils for embolization at the target site and promoting thrombosis. Embolization is a procedure in which coils are packed into the aneurysm, and it has three phases: Framing, Filling, and Finishing. In embolization, coils with different flexibility are generally selected for each phase. For example, in the Framing phase, it is necessary to lay the coils along the inner surface of the aneurysm to create a framework within the aneurysm. On the other hand, in the Filling and subsequent phases, coils with more flexibility than those used in Framing are selected because the coils are filled into the framework formed in Framing. Several to dozens of coils are used in a single embolization procedure. Patent Document 1 discloses an internal implantable device for embolus formation having a coil portion and an extension-restricting member placed inside the lumen, wherein the extension-restricting member has a wave-like shape. Patent Document 2 also discloses a vascular embolization device in which a resin wire containing a biochemically active substance is inserted inside a metal coil.

[0003] International Publication No. 2019 / 054066 JP 11-076249

[0004] The devices described in Patent Documents 1 and 2 had room for improvement in terms of sustained drug release. Therefore, the problem to be solved by this disclosure is to provide an in-vivo implantation device and an implantation system for the in-vivo implantation device that can enhance sustained drug release.

[0005] An in-vivo implantation device according to an embodiment of the present disclosure that can solve the above problems is as follows: [1] An in-vivo implantation device comprising: a coil having a lumen; and a stretch-resistance member disposed in the lumen and having a longitudinal axis direction, wherein the stretch-resistance member has a first cross-sectional shape perpendicular to the longitudinal axis direction at a first position in the longitudinal axis direction and a second cross-sectional shape perpendicular to the longitudinal axis direction at a second position in the longitudinal axis direction.

[0006] Furthermore, the in-vivo implantation device according to the embodiment is preferably any of the following [2] to [8]. [2] The in-vivo implantation device according to [1], wherein the first cross section has a flattened shape. [3] The in-vivo implantation device according to [2], wherein the second cross section has a flattened shape, and the degree of flatness, which is the value obtained by dividing the length of the major axis of the cross section perpendicular to the longitudinal axis of the stretch resistance member by the length of the minor axis, is higher for the first cross section than for the second cross section. [4] The in-vivo implantation device according to any one of [1] to [3], wherein the area of ​​the drug arranged in the first cross section is greater than the area of ​​the drug arranged in the second cross section. [5] The in-vivo implantation device according to any one of [1] to [4], wherein in the longitudinal axis direction, the first position is located distal to the second position. [6] The stretch resistance member has a wave-shaped portion having peaks and valleys in the longitudinal direction of the coil, the valley portion has a tip region on the valley bottom side and a base region on the peak side, the tip region of the valley portion has the first cross-section, and the base region of the valley portion has the second cross-section, as described in any one of [1] to [5]. [7] The stretch resistance member has a wave-shaped portion having peaks and valleys in the longitudinal direction of the coil, the peak portion has a tip region on the peak side and a base region on the valley side, the tip region of the peak portion has the first cross-section, and the base region of the peak portion has the second cross-section, as described in any one of [1] to [6]. [8] The stretch resistance member has a wave-shaped portion having peaks and valleys in the longitudinal direction of the coil, and the direction of the major axis of the first cross section is perpendicular to the amplitude direction of the wave-shaped portion and the direction perpendicular to the longitudinal direction of the coil, respectively, the in vivo implantation device according to any one of [1] to [7].

[0007] An implantation system for an in-vivo device according to an embodiment of the present disclosure that has been able to solve the above problems is as follows: [9] An implantation system for an in-vivo device comprising: a first coil having a lumen; a first stretch-resistance member disposed in the lumen of the first coil and having a longitudinal axis direction, wherein the stretch-resistance member has a drug on its surface; a second coil having a lumen and having a coil stiffness less than that of the first coil; and a second stretch-resistance member disposed in the lumen of the second coil and having a longitudinal axis direction, wherein the cross-sectional shape of the first stretch-resistance member perpendicular to the longitudinal axis direction and the cross-sectional shape of the second stretch-resistance member perpendicular to the longitudinal axis direction are different.

[0008] Furthermore, the implantation system for the in-vivo implantation device according to the embodiment is preferably any of the following

[10] to

[11] .

[10] The implantation system for the in-vivo implantation device according to [9], wherein the cross-section of the first stretch-resistant member has a flattened shape.

[11] The implantation system for the in-vivo implantation device according to

[10] , wherein the cross-section of the second stretch-resistant member has a flattened shape, and the degree of flatness, which is the value obtained by dividing the length of the major axis of the cross-section perpendicular to the longitudinal axis of the stretch-resistant member by the length of the minor axis, is higher for the cross-section of the first stretch-resistant member than for the cross-section of the second stretch-resistant member.

[0009] According to the above-described in-vivo implantation device, by making the shapes of the first and second cross-sections different, the outer diameter and circumference of the stretch-resistant member can be made different in these two cross-sections. As a result, the amount of drug distributed in the part with the first cross-section and the amount of drug distributed in the part with the second cross-section can be made different. This makes it possible to stagger the timing of drug release depending on the position of the stretch-resistant member in the longitudinal axis direction, thus making it easier to improve the sustained release of the drug.

[0010] According to the indwelling system of the above indwelling device in the body, by making the shapes of the cross-sections of the first extension resistance member and the second extension resistance member different, the outer diameter, outer circumference, etc. of the extension resistance member can be made different. Therefore, the amount of the drug arranged on the cross-section of the first extension resistance member and the amount of the drug arranged on the portion having the cross-section of the second extension resistance member can be made different. As a result, the timing of drug release from the first extension resistance member and the second extension resistance member can be shifted, so that it becomes easier to enhance the drug sustained-release property.

[0011] It is a schematic diagram of an indwelling device in the body according to an embodiment of the present disclosure. It is a cross-sectional view (partial side view) along the longitudinal direction of the coil of the indwelling device shown in FIG. 1. It is a side view of the extension resistance member of the indwelling device shown in FIG. 2 as viewed from the first direction, showing the peak portion and the valley portion. It is a front view of the extension resistance member shown in FIG. 3. It is a cut end face view of the V-V cross-section of the extension resistance member shown in FIG. 2, showing the shape of the first cross-section. It is a cut end face view of the VI-VI cross-section of the extension resistance member shown in FIG. 2, showing the shape of the second cross-section. It is a cut end face view showing a modified example of the extension resistance member shown in FIG. 6. It is a cut end face view of the VIII-VIII cross-section of the extension resistance member shown in FIG. 2, showing the shape of the third cross-section. It is a side view showing a modified example of the extension resistance member shown in FIG. 3. It is a side view showing a modified example of the extension resistance member shown in FIG. 3. It is a schematic diagram of an indwelling system of an indwelling device in the body according to an embodiment of the present disclosure. It is a cross-sectional view (partial side view) along the longitudinal direction of the first coil shown in FIG. 11. It is a cut end face view of the XIII-XIII cross-section of the first extension resistance member shown in FIG. 12. It is a cut end face view of the XIV-XIV cross-section of the first extension resistance member shown in FIG. 12. It is a cut end face view of the XV-XV cross-section of the first extension resistance member shown in FIG. 12. It is a cross-sectional view (partial side view) along the longitudinal direction of the second coil shown in FIG. 11. It is a cut end face view of the XVII-XVII cross-section of the first extension resistance member shown in FIG. 16. It is a cut end face view of the XVIII-XVIII cross-section of the first extension resistance member shown in FIG. 16. It is a cut end face view of the XIX-XIX cross-section of the first extension resistance member shown in FIG. 16.

[0012] Hereinafter, the content of the present disclosure will be described more specifically based on the following embodiments. However, the content of the present disclosure is not limited by the following embodiments, and it is of course possible to make appropriate modifications within the range that conforms to the gist of the foregoing and following descriptions and implement them, and all of them are included in the technical scope of the present disclosure. In each drawing, for the sake of convenience, hatching, member numbers, etc. may be omitted, but in such cases, reference shall be made to the specification and other drawings. Also, the dimensions of various members in the drawings may differ from the actual dimensions because priority is given to facilitating the understanding of the features of the present disclosure.

[0013] 1. Intravascular implant The intravascular implant according to an embodiment of the present disclosure includes a coil having a lumen and an extension resistance member disposed in the lumen and having a longitudinal axis direction, the surface of which is provided with a drug. The extension resistance member has a gist in that the shape of a first cross-section, which is a cross-section perpendicular to the longitudinal axis direction at a first position in the longitudinal axis direction, is different from the shape of a second cross-section, which is a cross-section perpendicular to the longitudinal axis direction at a second position in the longitudinal axis direction. Hereinafter, the intravascular implant may be simply referred to as an implant.

[0014] Examples of the use of the implant include embolization that promotes thrombosis at target sites such as cerebral aneurysms, aneurysms of the head and neck, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal arteries, and abdominal aneurysms. Among them, the implant is preferably an implant for cerebral aneurysms. Examples of the shape of the aneurysm include spindle-shaped and sac-shaped.

[0015] Embolization has Framing, Filling, and Finishing phases. The implant can be used in any one of the phases, or can be used over any two or three of the phases.

[0016] An in-vivo implantation device according to an embodiment of the present disclosure will be described with reference to Figures 1 to 10. Figure 1 is a schematic diagram of an in-vivo implantation device according to an embodiment of the present disclosure. Figure 2 is a cross-sectional view (partially a side view) along the longitudinal direction of the coil of the in-vivo implantation device shown in Figure 1. Figure 3 is a side view of the stretch resistance member of the in-vivo implantation device shown in Figure 2, viewed from a first direction, showing the peaks and valleys. Figure 4 is a front view of the stretch resistance member shown in Figure 3. Figure 5 is a cross-sectional end view of the stretch resistance member shown in Figure 2 at the V-V cross-section, showing the shape of the first cross-section. Figure 6 is a cross-sectional end view of the stretch resistance member shown in Figure 2 at the VI-VI cross-section, showing the shape of the second cross-section. Figure 7 is a cross-sectional end view showing a modified example of the stretch resistance member shown in Figure 6. Figure 8 is a cross-sectional end view of the stretch resistance member shown in Figure 2 at the VIII-VIII cross-section, showing the shape of the third cross-section. Figures 9 and 10 are side views showing modified examples of the stretch resistance member shown in Figure 3. As shown in Figure 2, the retaining device 1 has a coil 10 and a stretch resistance member 20.

[0017] As can be seen from Figure 2, the coil 10 preferably has a longitudinal direction x, a radial direction y, and a circumferential direction z. The coil 10 preferably has a distal end and a proximal end in the longitudinal direction x. The proximal side of the coil 10 refers to the direction toward the user or operator's hand with respect to the longitudinal direction x of the coil 10, and the distal side refers to the opposite direction from the proximal side, i.e., the direction toward the treatment target. In Figure 2, the right side of the figure is the proximal side, and the left side of the figure is the distal side. The radial direction y of the coil 10 refers to the radial direction of the coil 10, and in the radial direction y, inward refers to the direction toward the longitudinal axis center of the coil 10, and outward refers to the direction extending radially from the longitudinal axis center on the opposite side from the inward direction. The circumferential direction z of the coil 10 refers to the direction around the longitudinal axis. Hereinafter, in the longitudinal direction x of the coil 10, when the length of each member is divided into two equal parts, the proximal side may be referred to as the proximal part, and the distal side as the distal part.

[0018] In this specification, unless otherwise specified, coil 10 refers to the configuration in the primary coil state. A primary coil that has been further shaped into a helical or three-dimensional shape is sometimes called a secondary coil. It is preferable that the coil 10 of the primary coil, as shown in Figure 2, is shaped to form the secondary coil shown in Figure 1. In Figure 1, the primary coil is wound to form a three-dimensional secondary coil shape. The coil 10 of the implantation device 1 is inserted into the lumen of the transport catheter in the form of a linear primary coil, as shown in Figure 2, and transported to the target site. When the primary coil is pushed out of the catheter, it is placed in the aneurysm in a state that has unfolded into a three-dimensional shape, as shown in Figure 1, or in a state that conforms to the shape of the aneurysm.

[0019] As shown in Figure 2, the coil 10 has a lumen 11. Preferably, the lumen 11 extends in the longitudinal direction x. Preferably, the coil 10 has an outer circumferential surface 12 and an inner circumferential surface 13. The outer circumferential surface 12 faces the outside of the coil 10, i.e., the outside in the radial direction y, and the inner circumferential surface 13 faces the lumen 11. A stretch resistance member 20 is disposed in the lumen 11.

[0020] As shown in Figures 1 and 2, the coil 10 is preferably constructed by winding one or more wires 15 in a helical shape. Examples of wires 15 include single wires, stranded wires, and coils wound in a coil shape, with single wires being preferred. Furthermore, it is preferable that the wires 15 are not coils.

[0021] The wire 15 is preferably biocompatible and flexible. Examples of materials that make up the wire 15 include platinum, gold, titanium, tungsten and their alloys, stainless steel, and other metallic materials or combinations thereof. Among these, it is more preferable that the wire 15 is made of a platinum-tungsten alloy.

[0022] The wire 15 has a longitudinal axis direction and has a distal end and a proximal end in the longitudinal axis direction. The wire 15 may be composed of a single wire from the distal end to the proximal end, or it may be composed of multiple wires connected to each other in the longitudinal axis direction. The shape of the cross section perpendicular to the longitudinal axis direction of the wire 15 may be circular, oval, polygonal, or a combination thereof. The shape of the cross section perpendicular to the longitudinal axis direction of the wire 15 may be the same throughout the entire length of the wire 15 in the longitudinal axis direction, or it may differ depending on the position in the longitudinal axis direction.

[0023] The outer diameter of the wire 15 is not particularly limited, but may be, for example, 25 μm or more, 30 μm or more, or 35 μm or more, and may be 75 μm or less, or 70 μm or less.

[0024] The outer diameter of the wire 15 may be the same in the longitudinal direction of the wire 15, or it may be different depending on the position in the longitudinal direction of the wire 15. If the cross-section of the wire 15 is not circular, the outer diameter of the wire 15 shall refer to the diameter equivalent to a circle.

[0025] The coil 10 may be a single-layer coil or a multi-layer coil having multiple layers. A portion of the coil 10 in the longitudinal direction x may be a single layer, and the remaining portion may be multi-layer.

[0026] The density of the coil 10, i.e., the winding spacing, is not particularly limited and can be tightly wound, pitched, or a combination of these. The coil 10 may have adjacent wires 15 in contact with each other in the longitudinal direction x. The coil 10 may have adjacent wires 15 in contact with each other in only a part of the longitudinal direction x, or adjacent wires 15 in contact with each other throughout the entire longitudinal direction x. Furthermore, the coil 10 may not have adjacent wires 15 in contact with each other in the longitudinal direction x. The state of not being in contact means that there is a gap between adjacent wires 15 in the longitudinal direction x of the coil 10.

[0027] The shape of the cross-section of the coil 10 perpendicular to the longitudinal direction x may be circular, oval, polygonal, or a combination thereof. The oval shape includes elliptical, egg-shaped, and rounded rectangular shapes. The same applies in the following description.

[0028] The maximum and minimum outer diameters of the coil 10 are not particularly limited and can be appropriately selected according to the phase of the procedure. For example, they may be 150 μm or more, 180 μm or more, or 200 μm or more, and may also be 400 μm or less, 380 μm or less, or 350 μm or less.

[0029] The outer diameter and / or inner diameter of the coil 10 may be constant along the longitudinal direction x of the coil 10, or may vary in size depending on the position along the longitudinal direction x of the coil 10. If the cross-section of the coil 10 is not circular, the outer diameter of the coil 10 shall refer to the equivalent diameter. If the inner lumen cross-section of the coil 10 is not circular, the inner diameter of the coil 10 shall refer to the equivalent diameter. A constant outer diameter or inner diameter means that the outer diameter or inner diameter of the coil 10 is substantially constant over the entire longitudinal direction x of the coil 10, and includes cases where the change in the outer diameter or inner diameter of the coil 10 over the entire longitudinal direction x is within ±5%.

[0030] As shown in Figures 1 and 2, the retaining device 1 is positioned proximal to the coil 10 in the longitudinal direction x of the coil 10, and may further include a pusher 70 that pushes the coil 10 distally, and a connecting portion 75 that connects the proximal portion of the coil 10 and the distal portion of the pusher 70.

[0031] The pusher 70 is a rod-shaped or wire-shaped member used to hold the indwelling device 1 and push it distally. The pusher 70 can consist of one or more members. The pusher 70 can consist of a wire member, a coil member, or a combination thereof. The pusher 70 can be made of a conductive material such as stainless steel.

[0032] The connection portion 75 connects the coil 10 and the pusher 70. Preferably, the connection portion 75 has a detachment mechanism that allows the coil 10 to detach from the pusher 70. Examples of detachment mechanisms include hydraulic, electric, and mechanical types, and among these, an electric detachment mechanism is preferred. In the detachment mechanism, it is preferable that the connection portion 75 is heated and disconnected by electrical or thermal energy supplied through the pusher 70, causing the coil 10 to detach from the pusher 70. In this case, it is preferable that the connection portion 75 is heated by a high-frequency current supplied between the distal end of the pusher 70 and the counter electrode plate.

[0033] The connecting portion 75 preferably contains a material that melts or dissolves when heated. The connecting portion 75 can be cut by Joule heating. Examples of such materials include synthetic resin materials, and it is preferable to use hydrophilic resins of synthetic polymer substances such as polyvinyl alcohol (PVA), PVA crosslinked polymers, PVA water-absorbing gel freeze-thaw elastomers, and polyvinyl alcohol copolymers.

[0034] It is preferable that a portion of the connecting portion 75 (preferably the distal end) is inserted into the lumen 11 of the coil 10. It is preferable that a portion of the connecting portion 75 (preferably the proximal end) extends proximal to the proximal end of the coil 10.

[0035] The shape of the connecting portion 75 is not particularly limited and may be linear, rod-shaped, cylindrical, polygonal prism-shaped, cylindrical, polygonal tube-shaped, frustoconical, frustoconical, or a combination thereof.

[0036] As shown in Figures 1 and 2, the coil 10 is constructed by winding a wire 15, and the implantation device 1 may further have a tip 18 positioned at the distal end of the coil 10. The tip 18 covers a portion of the wire 15 to prevent the distal end of the wire 15 from directly contacting the inner wall surface of the body. The tip 18 may or may not be in contact with the stretch resistance member 20.

[0037] The shape of the tip 18 is not particularly limited, but may be, for example, hemispherical, semi-elongated, cylindrical, or polygonal prism.

[0038] The tip 18 may be joined to at least one of the outer circumferential surface 12 and the inner circumferential surface 13 of the coil 10. In addition, to prevent the tip 18 from falling off, a part of the tip 18 may be placed in the lumen 11 at the distal end of the coil 10. The proximal end of the tip 18 may be located distal to the distal end of the wire 15, and vice versa.

[0039] The tip 18 may be made of a metal material or a resin. Examples of resins that make up the tip 18 include thermoplastic resins and UV-curing resins. Examples of resins that make up the tip 18 include ester resins such as epoxy acrylate resins, urethane acrylate resins, polyester acrylate resins, and polyethylene terephthalate resins, and olefin resins such as polypropylene. As the metal that makes up the tip 18, the metals listed in the description of the wire 15 can be used. The materials of the wire 15 and the tip 18 may be the same or different.

[0040] As shown in Figures 1 and 2, a proximal tip 19 may be provided at the proximal end of the coil 10 to close the proximal end of the coil 10. The proximal tip 19 has a lumen, and a part of the connecting portion 75, for example, the distal end, may be inserted into the lumen. For the configuration of the proximal tip 19, refer to the description of the tip 18.

[0041] As shown in Figure 2, a stretch-resist member 20 having a longitudinal axis direction is disposed in the lumen 11. A drug 60 is disposed on the surface of the stretch-resist member 20. The stretch-resist member 20 suppresses the stretching of the coil 10 in the longitudinal direction x during operation.

[0042] The drug 60 may be the active ingredient (API) alone, or it may be a mixture with other additives. Preferred additives include base materials, plasticizers, stabilizers, surfactants, etc. In this specification, the amount of drug refers to the mass (mg) of drug 60. If drug 60 is a mixture containing additives, the amount of drug refers to the mass of the mixture in this specification.

[0043] The stretch resistance member 20 preferably has a longitudinal axis direction and has a first end and a second end in that longitudinal axis direction. The stretch resistance member 20 preferably extends from the distal end to the proximal end of the lumen 11.

[0044] The stretch resistance member 20 may be placed in the lumen 11 as a single unit, or multiple units may be placed therein.

[0045] The first end of the stretch resistance member 20 may be connected to the distal end of the coil 10, for example, the distal end of the wire 15. The second end of the stretch resistance member 20 may be connected to the proximal end of the coil 10, specifically the proximal end of the wire 15. The second end of the stretch resistance member 20 may be connected to the connection portion 75 that connects the coil 10 and the pusher 70.

[0046] Although not shown in the figures, it is preferable that the folded portion of the stretch resistance member 20, which is folded back in the middle of the longitudinal axis direction, is connected to the distal or proximal end of the coil 10, and that the first end and the second end are connected to the proximal or distal end of the coil 10, or to the distal end of the connecting portion 75.

[0047] The stretch resistance member 20 may be composed of a single member from the first end to the second end, or it may be composed of multiple members connected to each other in the longitudinal axis direction.

[0048] Methods for connecting the stretch resistance member 20 to other members include physical fixing methods such as welding, crimping, adhesive bonding, engagement, linking, binding, ligation, or combinations thereof. Here, "connection" includes both forms in which the two elements are directly connected and forms in which the two elements are indirectly connected through one or more other elements.

[0049] The stretch resistance member 20 may be made of resin or metal. Examples of resins that make up the stretch resistance member 20 include polyester resins such as polyethylene terephthalate, polyamide resins such as nylon, and polyolefin resins such as polyethylene and polypropylene. Examples of metals that make up the stretch resistance member 20 include platinum, gold, rhodium, palladium, rhenium, silver, nickel, titanium, tantalum, tungsten and their alloys, and stainless steel.

[0050] The stretch resistance member 20 may be made of a different material than the wire 15 that constitutes the coil 10. For example, the coil 10 may be made of a platinum-tungsten alloy, and the stretch resistance member 20 may be made of polypropylene resin.

[0051] As shown in Figures 5 and 6, the stretch-resist member 20 has a first cross-section 21a, which is perpendicular to the longitudinal axis at the first position 21 in the longitudinal axis direction, and a second cross-section 22a, which is perpendicular to the longitudinal axis at the second position 22 in the longitudinal axis direction, with different shapes. With the retaining device 1, by making the shapes of the first cross-section 21a and the second cross-section 22a different, the outer diameter and circumference of the stretch-resist member 20 can be made different in these two cross-sections 21a and 22a. As a result, the amount of drug 60 distributed in the part having the first cross-section 21a and the amount of drug 60 distributed in the part having the second cross-section 22a can be made different. This makes it possible to stagger the timing of drug release depending on the position of the stretch-resist member 20 in the longitudinal axis direction, making it easier to improve the sustained release of the drug.

[0052] As shown in Figures 2 and 3, the first position 21 and the second position 22 are arbitrary positions (points) along the longitudinal axis direction of the stretch resistance member 20. Preferably, the first position 21 and the second position 22 are separated in the longitudinal axis direction of the stretch resistance member 20. Preferably, the separation distance between the first position 21 and the second position 22 in the longitudinal axis direction of the stretch resistance member 20 is, for example, 10 mm or more and 30 mm or less. If the stretch resistance member 20 has a wave-shaped portion 40 as described later, the separation distance between the first position 21 and the second position 22 in the longitudinal axis direction of the stretch resistance member 20 may be more than 1 / 4 of the length of one crest in the wave propagation direction n and less than 1 / 2 of the length of that crest, or more than 1 / 4 of the length of one trough in the wave propagation direction n and less than 1 / 2 of the length of that trough. In the longitudinal direction x of the coil 10, the separation distance between the first position 21 and the second position 22 may be, for example, 10 mm or more and 30 mm or less. In the longitudinal axis direction, the first position 21 and the second position 22 may be distal or proximal, but it is preferable that the first position 21 is located distal to the second position 22.

[0053] The shape of the first cross-section 21a or the second cross-section 22a is the outline shape of the outer circumference of the cross-sectional figure of the stretch resistance member 20 in the first cross-section 21a or the second cross-section 22a. The outer circumference outline is composed of one or more sides. The outer circumference outline may have only straight sections, only curved sections, or both straight and curved sections, but it is preferable that it has only curved sections.

[0054] The shapes of the first cross-section 21a and the second cross-section 22a are different, meaning that one is not congruent to the other, and this includes the case where they are similar. "Congruent" includes cases where the cross-sectional figure of one of the first cross-section 21a and the second cross-section 22a coincides with the cross-sectional figure of the other after at least one of the operations of rotation, reflection, or translation. It is preferable that the shapes of the first cross-section 21a and the second cross-section 22a are not similar.

[0055] The shapes of the first cross-section 21a and the second cross-section 22a are not particularly limited and can be circular, oval, polygonal, a combination thereof, or an irregular shape. The oval shape includes elliptical, egg-shaped, and rounded rectangular shapes.

[0056] It is preferable that the outer diameter of the stretch-resistant member 20 in the first cross-section 21a is larger than the outer diameter of the stretch-resistant member 20 in the second cross-section 22a. This allows the amount of agent 60 distributed in the portion having the first cross-section 21a to be greater than the amount of agent 60 distributed in the portion having the second cross-section 22a. If the cross-section of the stretch-resistant member 20 is not a perfect circle, the outer diameter of the stretch-resistant member 20 refers to the diameter equivalent to a circle.

[0057] As shown in Figures 5 and 7, it is preferable that the length of the major axis 21b of the stretch resistance member 20 in the first cross-section 21a is longer than the length of the major axis 22b of the stretch resistance member 20 in the second cross-section 22a. The length of the major axis 21b may be shorter than the length of the major axis 22b, or the lengths of the major axis 21b and 22b may be the same.

[0058] As shown in Figures 5 and 7, it is preferable that the length of the minor axis 21c of the stretch resistance member 20 in the first cross-section 21a is shorter than the length of the minor axis 22c of the stretch resistance member 20 in the second cross-section 22a. The length of the minor axis 21c may be longer than the length of the minor axis 22c, or the lengths of the minor axis 21c and 22c may be the same.

[0059] The first cross-section 21a may have a non-flattened shape, but it is preferable to have a flattened shape as shown in Figure 5. This makes it easier to place a larger amount of drug in the portion having the first cross-section 21a.

[0060] As shown in Figure 6, the second cross-section 22a may have a non-flattened shape, or as shown in Figure 7, it may have a flattened shape. In Figure 6, the second cross-section 22a has a circular shape.

[0061] A flattened shape refers to a shape that is flat, where there is a difference between the length in one direction and the length in another direction perpendicular to the longitudinal axis of the cross-section perpendicular to the longitudinal axis. More specifically, a cross-sectional figure has a flattened shape if the flatness (aspect ratio), which is the value obtained by dividing the length of the major axis of the cross-section perpendicular to the longitudinal axis of the extension resistance member 20 by the length of the minor axis, is greater than 1.0, and a cross-sectional figure has a non-flattened shape if the flatness is 1.0.

[0062] Examples of non-flattened shapes include circles and regular polygons. Note that rounded regular polygons are also included in the category of non-flattened shapes.

[0063] Examples of flattened shapes include flattened circles formed by compressing a perfect circle in a specific direction, as well as oval shapes and polygons. Oval shapes include ellipses and egg shapes. Polygons include polygons with rounded corners and trapezoids.

[0064] As shown in Figure 5, the first cross-section 21a has a flattened shape, and as shown in Figure 7, the second cross-section 22a also has a flattened shape. In this case, the degree of flatness, which is the value obtained by dividing the length of the major axis of the cross-section perpendicular to the longitudinal axis of the stretch resistance member 20 by the length of the minor axis, is preferably higher for the first cross-section 21a than for the second cross-section 22a. This makes it easier to place more of the drug 60 in the portion having the first cross-section 21a compared to the portion having the second cross-section 22a.

[0065] If the first cross-section 21a has a flattened shape, the degree of flatness of the shape of the first cross-section 21a may be greater than 1.0, preferably 1.2 or more, more preferably 1.5 or more, and even more preferably 2.0 or more. The degree of flatness of the shape of the first cross-section 21a may be 10 or less, more preferably 8.0 or less, and even more preferably 5.0 or less.

[0066] The flatness of the shape of the second cross-section 22a should be greater than 1.0, preferably 1.1 or greater, more preferably 1.2 or greater, and even more preferably 1.3 or greater. The flatness of the shape of the second cross-section 22a should be 5.0 or less, more preferably 4.0 or less, and even more preferably 2.0 or less.

[0067] The flatness of the shape of the first cross-section 21a is preferably 1.1 times or more, more preferably 1.5 times or more, and even more preferably 2.0 times or more, the flatness of the shape of the second cross-section 22a is preferably 10 times or less, more preferably 8.0 times or less, and even more preferably 5.0 times or less, the flatness of the shape of the first cross-section 21a is preferably 10 times or less, more preferably 8.0 times or less, and even more preferably 5.0 times or less.

[0068] In the first cross section 21a or the second cross section 22a, the agent 60 may be distributed only to a part of the outer periphery of the cross-sectional figure, or it may be distributed over the entire outer periphery. In the first cross section 21a or the second cross section 22a, the thickness of the agent 60 may differ depending on the position on the outer periphery of the cross-sectional figure, or the agent 60 may be distributed with a uniform thickness over the entire outer periphery. Here, the thickness of the agent 60 refers to the thickness of the agent 60 in the radial direction, which is the direction from the centroid of the cross-sectional figure toward the outer periphery.

[0069] Preferably, the area of ​​the drug 60 arranged in the first cross-section 21a is greater than the area of ​​the drug 60 arranged in the second cross-section 22a. This makes it easier to increase the amount of drug in the portion having the first cross-section 22a compared to the portion having the second cross-section, and allows for a staggered timing of drug release, thereby improving the sustained release of the drug. The area of ​​the drug 60 arranged in the first cross-section 21a refers to the area of ​​the drug 60 arranged circumferentially outside one or more sides that constitute the outer contour of the first cross-section 21a, and excludes the area of ​​the drug contained inside the stretch resistance member 20. The area of ​​the drug 60 arranged in the second cross-section 22a is defined similarly.

[0070] The area of ​​the drug 60 arranged in the first cross section 21a is preferably 1.1 times or more, more preferably 1.2 times or more, and even more preferably 1.5 times or more, than the area of ​​the drug 60 arranged in the second cross section 22a. The area of ​​the drug 60 arranged in the first cross section 21a is preferably 10 times or less, more preferably 5.0 times or less, and even more preferably 3.0 times or less, than the area of ​​the drug 60 arranged in the second cross section 22a.

[0071] It is preferable that the first cross-section 21a and the second cross-section 22a are arranged alternately in the longitudinal axis direction of the stretch resistance member 20. The first cross-section 21a and the second cross-section 22a may be arranged periodically in the longitudinal axis direction of the stretch resistance member 20. Here, periodic means that the first cross-section 21a and the second cross-section 22a are arranged alternately at a constant interval.

[0072] In the longitudinal axis direction of the stretch-resistance member 20, flattened portions having a flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20 and non-flattened portions having a non-flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20 may be arranged alternately. In the longitudinal axis direction of the stretch-resistance member 20, first flattened portions having a flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20 and second flattened portions having a flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20 that is less flattened than the first flattened portions may be arranged alternately. In the longitudinal axis direction of the stretch-resistance member 20, a first flattened portion having a flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20, a second flattened portion having a flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20 that is less flattened than the first flattened portion, and a third flattened portion having a flattened cross-section perpendicular to the longitudinal axis direction of the stretch-resistance member 20 that is less flattened than the first flattened portion and more flattened than the second flattened portion may be arranged alternately. Preferably, the flattened portion, the first flattened portion, and the second flattened portion include at least one of the peaks 41 or troughs 45 of the wave-shaped portion 40. Preferably, the third flattened portion includes the boundary position between the peaks 41 and troughs 45 of the wave-shaped portion 40 (the position where it intersects with the reference line BL). Preferably, the first flattened section includes the summit of the mountain section 41, the second flattened section includes the boundary between the mountain section 41 and the valley section 45, and the third flattened section includes the bottom of the valley section 45.

[0073] Although not shown in the figures, the stretch resistance member 20 has a first portion and a second portion in the longitudinal axis direction, and the shape of the cross-section perpendicular to the longitudinal axis direction in the first portion and the shape of the cross-section perpendicular to the longitudinal axis direction in the second portion may be different from each other. Preferably, the first portion is located distal to the second portion. For the cross-sectional shape of the first portion, refer to the description of the shape of the first cross-section 21a at the first position 21. For the cross-sectional shape of the second portion, refer to the description of the shape of the second cross-section 22a at the second position 22.

[0074] The stretch resistance member 20 may be configured to gradually change from the shape of the first cross-section 21a to the shape of the second cross-section 22a as it moves from the first position 21 to the second position 22 in the longitudinal axis direction.

[0075] As shown in Figures 2, 6 to 8, in the stretch-resistance member 20, the shape of the third cross-section 23a, which is a cross-section perpendicular to the longitudinal axis at the third position 23 in the longitudinal axis direction, may differ from the shape of the second cross-section 22a. Since the outer diameter and circumference of the stretch-resistance member 20 can be made different in the two cross-sections, the amount of drug 60 distributed in the portion having the third cross-section 23a can be made different from the amount of drug 60 distributed in the portion having the second cross-section 22a. As a result, the timing of drug release can be shifted depending on the position of the stretch-resistance member 20 in the longitudinal axis direction, making it easier to improve the sustained release of the drug. Note that the shape of the third cross-section 23a may be the same as or different from the shape of the first cross-section 21a.

[0076] The third position 23 is any position along the longitudinal axis. As shown in Figure 2, it is preferable that the third position 23 is located proximal to the first position 21 in the longitudinal axis direction. It is also preferable that the third position 23 is located proximal to the second position 22. It is also preferable that the second position 22 is located between the first position 21 and the third position 23 in the longitudinal axis direction. The second position 22 may be located on the midpoint that bisects the length from the first position 21 to the third position 23 in the longitudinal axis direction.

[0077] For the shape of the third cross-section 23a, refer to the description of the shape of the first cross-section 21a.

[0078] The type of drug 60 is not particularly limited as long as it is necessary for the prevention or treatment of the affected area. Preferably, drug 60 has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, vasoconstriction inhibitory effect, anticoagulant effect, and shear stress sensing inhibitory effect, and more preferably, it has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, and vasoconstriction inhibitory effect. Examples of drugs 60 include selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, sertraline, paroxetine, etc.), DPP-4 inhibitors (sitagliptin, linagliptin, alogliptin, etc.), HMG-CoA reductase inhibitors (atorvastatin, pitavastatin, rosuvastatin, pravastatin, simvastatin, fluvastatin, lovastatin, mevastatin, cerivastatin, etc.), nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, naproxen, celecoxib, etc.), angiotensin II receptor blockers (ARBs) (losartan, valsartan, telmisartan, etc.), tocopherol acetate (vitamin E acetate, eviprostat, estrol, etc.), ascorbic acid (Asconal, Cinal, Cefylol), and edaravone (Radicut, Free Radical Scavenging). Examples include anticoagulants (such as prazosin, terazosin, and doxazosin), N-acetyl-L-cysteine ​​(NAC), calcium channel blockers (such as amlodipine, nifedipine, and diltiazem), diuretics (such as furosemide, trichlormethiazide, and spironolactone), angiotensin-converting enzyme inhibitors (ACEs) (such as enalapril, lisinopril, and perindopril), beta-blockers (such as metoprolol, atenolol, and bisoprolol), alpha-blockers (such as prazosin, terazosin, and doxazosin), alpha-beta-blockers (such as carvedilol, labetalol, and butoxamine), nitrates (such as nitroglycerin and isosorbide dinitrate), prostacyclin analogs (such as epoprostenol and treprostinil), anticoagulants (such as heparin, heparin derivatives, warfarin, antithrombin drugs such as dabigatran, and rivaroxaban), and antiplatelet agents (such as aspirin, clopidogrel, and ticagrelor).

[0079] The drug 60 may be directly attached to the surface of the stretch-resistant member 20, or it may be indirectly attached to the surface of the stretch-resistant member 20 via a bioadhesive. The type of material of the bioadhesive is not particularly limited, but for example, polysaccharide adhesives such as collagen, chitosan, and gelatin, polyethylene glycol-based hydrogel adhesives, and protein adhesives such as fibrin and collagen can be used.

[0080] The drug 60 may be encapsulated in a capsule. The drug 60 encapsulated in the capsule may be directly attached to the surface of the stretch-resistant member 20, or it may be attached indirectly to the surface of the stretch-resistant member 20 via a bioadhesive. The size of the capsule is preferably 10 nm or larger, more preferably 50 nm or larger, even more preferably 100 nm or larger, and preferably 500 nm or smaller, more preferably 400 nm or smaller, and even more preferably 200 nm or smaller. The capsule is preferably made of a biodegradable material. As the biodegradable material, bioabsorbable polymers, natural polymers, decellularized biological tissues or cells, or combinations thereof can be used. As the bioabsorbable polymer, at least one of polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), copolymer of lactic acid and glycolic acid (PLGA), polycaprolactone (PCL), and polydioxanone (PDS) is preferably used. Furthermore, at least one of the following natural polymers is preferably used: collagen, laminin, fibroin, gelatin, glycosaminoglycan, chitin, chitosan, hyaluronic acid, and polypeptide.

[0081] The drug 60 may be distributed only in a portion of the longitudinal axis direction of the stretch-resistance member 20, or it may be distributed over the entire longitudinal axis direction of the stretch-resistance member 20. The drug 60 may be distributed only in a portion of the circumferential direction of the stretch-resistance member 20, or it may be distributed over the entire circumferential direction of the stretch-resistance member 20. The longitudinal axis direction of the stretch-resistance member 20 is the direction along the waveform in the wave-shaped portion 40 of the stretch-resistance member 20. The circumferential direction of the stretch-resistance member 20 is the direction around the longitudinal axis of the stretch-resistance member 20.

[0082] As shown in Figures 2, 3, 9, and 10, it is preferable that the stretch resistance member 20 has a wave-shaped portion 40 having peaks 41 and valleys 45 in sequence in the longitudinal direction x of the coil 10.

[0083] The peaks 41 and valleys 45 are defined using a reference line BL virtually applied to the stretch resistance member 20. First, as shown in Figures 2 and 3, the primary coil is extended in a straight line such that the distal end of the primary coil is on the left side from the user's perspective and the proximal end of the primary coil is on the right side, and the stretch resistance member 20 is positioned such that its length is maximized in the radial direction y of the coil 10. The direction from the user toward the coil 10 is defined as the first direction d1 (see Figure 4). When the stretch resistance member 20 is viewed from the first direction d1, it is preferable that the stretch resistance member 20 has an upward convex portion and a downward convex portion arranged in such a way as at least one of the following (i), (ii), and (iii): (i) A downward convex portion 31a, an upward convex portion 32a, and a downward convex portion 31b are arranged in this order in the longitudinal direction x from the distal end toward the proximal end (Figures 3 and 10). (ii) The downward-facing protrusion 31a, the upward-facing protrusion 32a, the upward-facing protrusion 32b, and the downward-facing protrusion 31b are arranged in this order along the longitudinal direction x from distal to proximal (Figure 9). (iii) The upward-facing protrusion 32a, the downward-facing protrusion 31a, the downward-facing protrusion 31b, and the upward-facing protrusion 32b are arranged in this order along the longitudinal direction x from distal to proximal (not shown). As shown in Figures 3 and 10, in case (i), the midpoint P1 of the first line segment LS1 is defined as connecting the uppermost end 31a1 of the downward projection 31a and the uppermost end 32a1 of the upward projection 32a adjacent to the proximal side of the projection 31a, and the midpoint P2 of the second line segment LS2 is defined as connecting the uppermost end 32a1 of the upward projection 32a and the uppermost end 31b1 of the downward projection 31b adjacent to the proximal side of the projection 32a. As shown in Figure 9, in case (ii), the midpoint P1 of the first line segment LS1 is defined as the point connecting the uppermost end 31a1 of the downward projection 31a and the uppermost end 32a1 of the upward projection 32a adjacent to the proximal side of the projection 31a, and the midpoint P2 of the second line segment LS2 is defined as the point connecting the uppermost end 32b1 of the upward projection 32b adjacent to the proximal side of the projection 32a and the uppermost end 31b1 of the downward projection 31b adjacent to the proximal side of the projection 32b.Although not shown in the illustration, as can be understood from Figure 9, in case (iii), the midpoint P1 of the first line segment LS1 is defined as the point connecting the uppermost end 32a1 of the upward-facing protrusion 32a and the uppermost end 31a1 of the downward-facing protrusion 31a adjacent to the proximal side of the protrusion 32a. The midpoint P2 of the second line segment LS2 is defined as the point connecting the uppermost end 31b1 of the downward-facing protrusion 31b adjacent to the proximal side of the protrusion 31a and the uppermost end 32b1 of the upward-facing protrusion 32b adjacent to the proximal side of the protrusion 31b. In all cases from (i) to (iii), the straight line passing through the two midpoints P1 and P2 is defined as the reference line BL, and the portion of the stretch resistance member 20 that protrudes above the reference line BL in the radial direction y is defined as the peak portion 41, and the portion that protrudes below the reference line BL in the radial direction y is defined as the valley portion 45.

[0084] As shown in Figure 3, it is preferable that the wave-shaped portion 40 has a wave amplitude direction m and a wave propagation direction n perpendicular to the amplitude direction. It is preferable that the amplitude direction m is parallel to the radial direction y when viewed from the first direction d1. It is preferable that the wave propagation direction n is parallel to the reference line BL. It is also preferable that the wave propagation direction n is parallel to the longitudinal direction x of the coil 10. It is preferable that the wave propagation direction n is parallel to the direction from the distal end to the proximal end of the coil 10.

[0085] As shown in Figure 3, the wave-shaped portion 40 preferably includes at least one peak 41 and two valleys 45, and more preferably includes multiple peaks 41 and multiple valleys 45. In the wave-shaped portion 40, it is preferable that the peaks 41 and valleys 45 are arranged adjacent to each other in the longitudinal direction x. As shown in Figure 9, the stretch resistance member 20 may have a straight portion 49 that extends between the peaks 41 and valleys 45 so as to overlap with the reference line BL.

[0086] The wave-shaped portion 40 may have a non-periodic wave shape, but it is preferable that it has a periodic wave shape as shown in Figure 3. In the wave-shaped portion 40, it is preferable that multiple sets of peaks 41 and troughs 45 are arranged continuously in the longitudinal direction x of the coil 10. It is preferable that the peaks 41 and troughs 45 are adjacent to each other.

[0087] In the wave-shaped portion 40, the amplitude of the peaks 41 and the amplitude of the troughs 45 may be the same or different. For example, the amplitude of the troughs 45 may be larger than the amplitude of the peaks 41. In this case, it becomes easier to apply even more of the drug 60 to the troughs 45. The amplitude of the peaks 41 is the distance from the reference line BL in the amplitude direction m to the uppermost point 41a of the peaks 41. The amplitude of the troughs 45 is the distance from the reference line BL in the amplitude direction m to the uppermost point 45a of the troughs 45.

[0088] In the wave-shaped portion 40, the number of peaks 41 may be greater than the number of valleys 45, but it is preferable that the number of valleys 45 be greater than the number of peaks 41. This increases the amount of drug held by the stretch resistance member 20.

[0089] In the wave-shaped portion 40, the peaks 41 and troughs 45 may be the same length or different lengths in the longitudinal direction x of the coil 10. For example, it is preferable that one trough 45 is longer than one peak 41 in the longitudinal direction x of the coil 10. It is also preferable that the total length of all troughs 45 is longer than the total length of all peaks 41 in the longitudinal direction x of the coil 10.

[0090] The wave-shaped portion 40 may be arranged individually or in multiples on a single stretch resistance member 20. The wave-shaped portions 40 may be arranged continuously or intermittently in the longitudinal direction x.

[0091] The shape of the wave-shaped portion 40 is preferably a plane wave shape. Examples of wave-shaped portions 40 include a rectangular wave shape, a triangular wave shape, and a sinusoidal wave shape, but a sinusoidal wave shape is more preferable.

[0092] The wave-shaped portion 40 may be arranged only in a part of the longitudinal axis direction of the stretch resistance member 20, or it may be arranged over the entire longitudinal axis direction of the stretch resistance member 20. The portion of the stretch resistance member 20 other than the wave-shaped portion 40 may be, for example, linear or helical. For example, in Figure 9, a linear portion 49 is arranged between two wave-shaped portions 40.

[0093] As shown in Figure 10, the valley portion 45 may have a tip region 45b on the valley bottom side and a base region 45c on the peak portion 41 side, both of which have equal lengths in the amplitude direction m of the wave-shaped portion 40. In this case, it is preferable that the tip region 45b of the valley portion 45 has a first cross-section 21a and the base region 45c of the valley portion 45 has a second cross-section 22a. This makes it easier for the tip region 45b of the valley portion 45 having the first cross-section 21a to hold a larger amount of drug on the surface of the stretch resistance member 20 than the base region 45c of the valley portion 45 having the second cross-section 22a.

[0094] Preferably, the amount of drug per unit length in the longitudinal direction x of the coil 10 at the tip region 45b of the valley 45 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 at the base region 45c of the valley 45.

[0095] As shown in Figure 10, the peak portion 41 may have a peak-side tip region 41b and a trough-side base region 41c, both of which have equal lengths in the amplitude direction m of the wave-shaped portion 40. In this case, it is preferable that the tip region 41b of the peak portion 41 has a first cross-section 21a and the base region 41c of the peak portion 41 has a second cross-section 22a. This makes it easier for the tip region 41b of the peak portion 41 having the first cross-section 21a to hold a larger amount of drug on the surface of the stretch-resistant member 20 than the base region 41c of the peak portion 41 having the second cross-section 22a.

[0096] Preferably, the amount of drug per unit length in the longitudinal direction x of the coil 10 at the tip region 41b of the peak 41 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 at the base region 41c of the peak 41.

[0097] For the tip region 41b and base region 41c of the peak portion 41 and / or the tip region 45b and base region 45c of the valley portion 45, the amount of drug in each region and the length of the coil 10 in the longitudinal direction x may be measured after separating the peak portion 41 and / or valley portion 45 into the tip region 45b and base region 45c using a laser cutting device or the like, or they may be measured with the stretch resistance member 20 fixed to the in-vivo implantation device 1.

[0098] If the stretch resistance member 20 has a wave-shaped portion 40, it is preferable that the direction of the major axis of the first cross section 21a is perpendicular to the amplitude direction m of the wave-shaped portion 40 and the direction perpendicular to the longitudinal direction x of the coil 10. This makes it easier to place the drug 60 on the portion having the first cross section 21a. If the second cross section 22a has a major axis, it is preferable that the direction of the major axis of the second cross section 22a is perpendicular to the amplitude direction m of the wave-shaped portion 40 and the direction perpendicular to the longitudinal direction x of the coil 10. This makes it easier to place the drug 60 on the portion having the second cross section 22a.

[0099] In the retaining device 1, it is preferable that the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley portion 45 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 41. As the stretching of the coil 10 pulls the stretching resistance member 20 in the direction of stretching, cracks are more likely to form in the drug 60 in the valley portion 45 where more drug 60 is attached than in the peak portion 41. Since the release of drug 60 is promoted by the cracks, the release of drug 60 can be performed efficiently.

[0100] The amount of drug per unit length in the longitudinal direction x of the coil 10 at the peaks 41 (mg / mm) can be determined by dividing the total amount of drug 60 distributed in the peaks 41 by the total length of the peaks 41 in the longitudinal direction x of the coil 10 (primary coil). The amount of drug per unit length in the longitudinal direction x of the coil 10 at the valleys 45 (mg / mm) can be determined by dividing the total amount of drug 60 distributed in the valleys 45 by the total length of the valleys 45 in the longitudinal direction x of the coil 10 (primary coil). If the stretch resistance member 20 has multiple peaks 41, the total amount of drug 60 distributed in the peaks 41 refers to the total amount of drug 60 distributed in those multiple peaks 41. The same applies to the total amount of drug 60 distributed in the valleys 45. The total amount of the drug 60 in the peaks 41 and valleys 45, and / or the lengths of the peaks 41 and valleys 45, may be measured after separating the stretch resistance member 20 into the peaks 41 and valleys 45 using a laser cutting device or the like. The lengths of the peaks 41 and valleys 45 may also be measured while the stretch resistance member 20 is fixed to the coil 10.

[0101] The same method shall be used to measure the amount of drug per unit length in the longitudinal direction x of the coil 10 at the peaks 41 and valleys 45. The amount of drug per unit length (mg / mm) of the coil 10 can be measured using various elemental analyzers, such as a Raman spectrophotometer, a near-infrared spectrophotometer, or an X-ray fluorescence analyzer. The amount of drug per unit length of the coil 10 may also be determined by extracting the drug 60 contained in the coil 10 with a solvent and analyzing its concentration. The type of solvent is not particularly limited, but for example, ethanol, methanol, acetone, ethyl acetate, acetonitrile, N,N-dimethylacetamide, propanol, chloroform, and benzyl alcohol can be used.

[0102] 2. Intra-vivo device placement system: Hereafter, the intra-vivo device placement system may be simply referred to as the "system."

[0103] The system according to the embodiment of the present disclosure will be described with reference to Figures 11 to 19. Figure 11 is a schematic diagram of the implantation system for an in-vivo implantation device according to the embodiment of the present disclosure. Figure 12 is a cross-sectional view (partially a side view) along the longitudinal direction of the first coil shown in Figure 11. Figure 13 is a cut end view of the first stretch resistance member shown in Figure 12 at the XIII-XIII cross section. Figure 14 is a cut end view of the first stretch resistance member shown in Figure 12 at the XIV-XIV cross section. Figure 15 is a cut end view of the first stretch resistance member shown in Figure 12 at the XV-XV cross section. Figure 16 is a cross-sectional view (partially a side view) along the longitudinal direction of the second coil shown in Figure 11. Figure 17 is a cut end view of the first stretch resistance member shown in Figure 16 at the XVII-XVII cross section. Figure 18 is a cross-sectional end view of the first stretch-resistance member shown in Figure 16 at the XVIII-XVIII section. Figure 19 is a cross-sectional end view of the first stretch-resistance member shown in Figure 16 at the XIX-XIX section. As shown in Figure 11, the system 100 comprises a first in-vivo implantation device 10A and a second in-vivo implantation device 10B.

[0104] As shown in Figure 12, the first in-vivo implantation device 10A has a first coil 101 having a lumen 111, and a first stretch-resistance member 201 positioned in the lumen 111 of the first coil 101 and having a longitudinal axis direction. Drug 601 is placed on the surface of the first stretch-resistance member 201. As shown in Figure 16, the second in-vivo implantation device 10B has a second coil 102 having a lumen 112 and having a lower coil stiffness than the first coil 101, and a second stretch-resistance member 202 positioned in the lumen 112 of the second coil 102 and having a longitudinal axis direction. Drug 602 is placed on the surface of the second stretch-resistance member 202. As can be seen from Figures 13 to 15 and Figures 17 to 19, in system 100, the cross-sectional shape perpendicular to the longitudinal axis direction of the first stretch-resistance member 201 and the cross-sectional shape perpendicular to the longitudinal axis direction of the second stretch-resistance member 202 are different. According to system 100, by making the cross-sectional shapes of the first stretch-resistance member 201 and the second stretch-resistance member 202 different, the outer diameter and circumference of the stretch-resistance members can be made different. As a result, the amount of drug distributed in the cross-section of the first stretch-resistance member 201 and the amount of drug distributed in the portion of the second stretch-resistance member 202 having the same cross-section can be made different. This makes it possible to stagger the timing of drug release from the first stretch-resistance member 201 and the second stretch-resistance member 202, making it easier to improve the sustained release of the drug.

[0105] For details on the configuration of the first coil 101 and the second coil 102, please refer to the explanation of coil 10 in "1. Intra-vivo implantation device".

[0106] It is preferable that the first coil 101 is inserted into the body before the second coil 102.

[0107] The first coil 101 is harder than the second coil 102. By combining the first coil 101 and the second coil 102 in this way, it becomes easier to apply the necessary amount of medication to the affected area.

[0108] As shown in FIG. 12, the first coil 101 is preferably formed from the first wire 151. As shown in FIG. 16, the second coil 102 is preferably formed from the second wire 152. For the first wire 151 and the second wire 152, reference can be made to the description of the wire in "1. Implant in the body".

[0109] In this specification, the hardness of the coil refers to the coil hardness in the state of the primary coil. The coil hardness S of the first coil 101 (primary coil) １ (unit: N / mm) and the coil hardness S of the second coil 102 (primary coil) ２ (unit: N / mm) can be calculated by the following formula. S １ = D １１ ４ × G / (8D １２ ３ × n １ ) S ２ = D ２１ ４ × G / (8D ２２ ３ × n ２ ) Here, D １１ is the outer diameter of the first wire 151 (unit: mm), G is the shear modulus of elasticity (unit: Pa (N / mm ２ )), D １２ is the outer diameter of the first coil 101 (unit: mm), n １ is the number of turns of the first coil 101 (unitless), D ２１ is the outer diameter of the second wire 152 (unit: mm), D ２２ is the outer diameter of the second coil 102 (unit: mm), n ２ is the number of turns of the second coil 102 (unitless). When the outer diameter of the first wire 151 is not constant in the longitudinal axis direction of the first wire 151, the outer diameter D of the first wire 151 １１ refers to the average value of the outer diameter in the longitudinal axis direction of the first wire 151. The same applies to the outer diameter D of the second wire 152 ２１ . When the outer diameter of the first coil 101 is not constant in the longitudinal direction x of the first coil 101, the outer diameter D of the first coil 101 １２ refers to the average value of the outer diameter in the longitudinal direction x of the first coil 101. The same applies to the outer diameter D of the second coil 102 ２２ . The number of turns n of the first coil 101 １n refers to the number of turns when the first coil 101 is viewed from the side at the angle that maximizes the number of turns. ２ The same applies to the following. The shear modulus G is a different value for each material constituting the wire, and if the chemical composition of the constituting materials of the wire is the same, the value of the shear modulus G will be the same. The same applies to the following explanation. It is preferable that the stiffness of the coil be calculated in the state before the application of the chemical. For coils with chemicals or coatings applied to the surface, the stiffness of the coil shall be measured after removing them. The method for removing the chemicals or coatings is not limited, but for example, a method of dissolving them in an organic solvent such as ethanol, methanol, or chloroform can be used.

[0110] When calculating the coil hardness, the outer diameter D of the first wire 151 is used. １１ , outer diameter D of the first coil 101 １２ , outer diameter D of the second wire 152 ２１ , the outer diameter D of the second coil 102 ２２ Alternatively, values ​​measured by measuring means such as calipers, micrometers, or image dimension measuring instruments may be used.

[0111] When calculating the coil hardness, the outer diameter D of the first wire 151 is used. １１ , outer diameter D of the first coil 101 １２ , Number of turns of the first coil 101 n １ , outer diameter D of the second wire 152 ２１ , the outer diameter D of the second coil 102 ２２ , Number of turns of the second coil 102 n ２ At least one of these values ​​may be the one listed in the coil's product catalog.

[0112] In the longitudinal direction x, the lengths of the first coil 101 and the second coil 102 may be the same or different. In the longitudinal direction x, the second coil 102 may be longer than the first coil 101. In the longitudinal direction x, the first coil 101 may be longer than the second coil 102.

[0113] Outer diameter D of the first wire 151 １１ and the outer diameter D of the second wire 152 ２１The same size is acceptable. Outer diameter D of the first wire 151 １１ and the outer diameter D of the second wire 152 ２１ The sizes of the first coils may be different. The outer diameter D of the first wire 151 is such that the first coil 101 is more likely to be stiffer than the second coil 102. １１ The outer diameter D of the second wire 152 is ２１ It may be larger than this. Note that the outer diameter D of the first wire 151 １１ The outer diameter D of the second wire 152 is ２１ It can be smaller than that.

[0114] Outer diameter D of the first coil 101 １２ and the outer diameter D of the second coil 102 ２２ The outer diameter D of the first coil 101 may be the same size. １２ and the outer diameter D of the second coil 102 ２２ The sizes of the first coil 101 may be different from each other. The outer diameter D of the first coil 101 should be such that the first coil 101 is more likely to be rigid than the second coil 102. １２ The outer diameter D of the second coil 102 is ２２ It may be smaller than this. Note that the outer diameter D of the first coil 101 is also smaller. １２ The outer diameter D of the second coil 102 is ２２ It may be larger than this. Here, the outer diameter D of the first coil 101 １２ and the outer diameter D of the second coil 102 ２２ These terms refer to the average values ​​of the outer diameter in the longitudinal direction x of the coil.

[0115] The coil hardness of the first coil 101 is 5.0 × 10 －９ It is preferable that the hardness is N / mm or greater. A first coil 101 having such hardness can suppress the impact on the reduction of operability even if it hardens due to the application of a chemical agent.

[0116] The coil hardness of the first coil 101 is 8.0 x 10 －９ It is more preferable that the ratio be N / mm or higher, and 1.0 × 10 －８ It is even more preferable that the coefficient of gravity is N / mm or greater. Also, the coil hardness of the first coil 101 is 3.5 × 10 －８ It is preferable that the value is less than N / mm, and 3.0 × 10 －８ N / mm or less, 2.0×10 －８A stiffness of N / mm or less is also acceptable. By distributing the drug in a coil of this stiffness, it is possible to apply the necessary amount of drug to the affected area while minimizing the impact on operability.

[0117] The coil hardness of the second coil 102 is 5.0 × 10 －９ It is preferable that the hardness is less than N / mm. Since the second coil 102 having such hardness retains its flexibility even when drug is applied, the coil can be placed in the aneurysm while ensuring maneuverability. The coil hardness of the second coil 102 is 1.0 × 10⁻⁶. －９ N / mm or more, 2.0×10 －９ It may be N / mm or greater, and also 4.0 × 10 －９ N / mm or less, 3.0×10 －９ A value of N / mm or less is also acceptable.

[0118] As shown in Figures 12 and 16, in system 100, the agents 601 and 602 are placed on the surface of the first stretch-resistant member 201 and the surface of the second stretch-resistant member 202, respectively. The amount of agent on the surface of the second stretch-resistant member 202 may be such that the amount of agent per unit length of the stretch-resistant member (mg / mm) is less than that of the first stretch-resistant member 201.

[0119] Although not shown in the diagram, in system 100, the drug may be placed on the surface of the first coil 101 and the surface of the second coil 102, respectively. The drug on the surface of the second coil 102 may be placed such that the amount of drug per unit length of the coil (mg / mm) is less than that of the first coil 101. This maintains the flexibility of the second coil 102, allowing the coil to be placed in the aneurysm while ensuring maneuverability.

[0120] For the configuration of the first stretch-resistant member 201 and the second stretch-resistant member 202, refer to the description of the stretch-resistant member 20 in "1. Intra-vivo device". For the shape of the cross-section of the first stretch-resistant member 201 perpendicular to the longitudinal axis, refer to the description of the shape of the first cross-section 21a in "1. Intra-vivo device". For the shape of the cross-section of the second stretch-resistant member 202 perpendicular to the longitudinal axis, refer to the description of the shape of the second cross-section 22a in "1. Intra-vivo device".

[0121] As shown in Figures 13 to 15, it is preferable that the cross-section of the first stretch-resistance member 201 has a flattened shape. In the flattened portion, it is easier to place the drug on the surface of the first stretch-resistance member 201, so that the amount of drug placed on the first stretch-resistance member 201 can be increased.

[0122] The shape of the cross-section perpendicular to the longitudinal axis may differ or be the same depending on the position of the first stretch-resistance member 201 in the longitudinal axis direction. Figure 13 shows a cross-section at the bottom of the valley 451, Figure 14 shows a cross-section at the boundary between the valley 451 and the peak 411, and Figure 15 shows a cross-section at the peak of the peak 411. In these drawings, the cross-sectional shape is the same in Figures 13 and 15, while the cross-sectional shape differs between Figure 14 and Figures 13 and 15. In detail, Figures 13 and 15 are flatter than Figure 14. By changing the shape of the cross-section in this way, the outer diameter and circumference of the stretch-resistance member can be varied, and therefore the amount of drug can be varied depending on the position of the first stretch-resistance member 201 in the longitudinal axis direction.

[0123] The amount of the agent 601 distributed on the surface of the first stretch-resistance member 201 may differ depending on its position in the longitudinal axis direction. For example, in the cross-sections shown in Figures 13 to 15, the area of ​​the agent 601 is different in each case.

[0124] The shape of the cross-section perpendicular to the longitudinal axis may differ or be the same depending on the position of the second stretch-resistance member 202 in the longitudinal axis direction. Figure 17 shows a cross-section at the bottom of the valley 452, Figure 18 shows a cross-section at the boundary between the valley 452 and the peak 412, and Figure 19 shows a cross-section at the peak of the peak 412. In these drawings, the cross-sectional shape is the same in Figures 17 and 19, while the cross-sectional shape differs between Figure 18 and Figures 17 and 19. In detail, Figures 17 and 19 are flatter than Figure 18. By changing the shape of the cross-section in this way, the outer diameter and circumference of the stretch-resistance member can be varied, and therefore the amount of drug can be varied depending on the position of the second stretch-resistance member 202 in the longitudinal axis direction.

[0125] The amount of the agent 602 distributed on the surface of the second stretch-resistance member 202 may differ depending on its position in the longitudinal axis direction. For example, in the cross-sections shown in Figures 17 to 19, the area of ​​the agent 602 is different in each case.

[0126] As shown in Figures 17 to 19, it is preferable that the cross-section of the second stretch-resistance member 202 has a flattened shape. In the flattened portion, it is easier to place the drug on the surface of the second stretch-resistance member 202, so that the amount of drug placed on the second stretch-resistance member 202 can be increased.

[0127] As can be seen from Figures 13 to 15 and Figures 17 to 19, the cross-section of the second stretch-resistance member 202 has a flattened shape, and the flatness, which is the value obtained by dividing the length of the major axis of the cross-section perpendicular to the longitudinal axis of the stretch-resistance member by the length of the minor axis, is preferably higher for the cross-section of the first stretch-resistance member 201 than for the cross-section of the second stretch-resistance member 202. This makes it easier to place the drug on the surface of the first stretch-resistance member 201 compared to the second stretch-resistance member 202. In addition, by reducing the amount of drug carried by the second in-vivo implantation device 10B, which is preferably inserted into the body after the first in-vivo implantation device 10A, the second coil 102 can be formed more flexibly, making it easier to pack the coil into the nodule.

[0128] As shown in Figures 12 and 16, when the first stretch-resistant member 201 has a wave-shaped portion 401, which has peaks 411 and valleys 451, and the second stretch-resistant member 202 has a wave-shaped portion 402, which has peaks 412 and valleys 452, as shown in Figures 13 and 17, it is preferable that the flatness of the cross section perpendicular to the longitudinal axis at the valley 451 of the first stretch-resistant member 201 is higher than the flatness of the cross section perpendicular to the longitudinal axis at the valley 452 of the second stretch-resistant member, and it is even more preferable that the flatness of the cross section perpendicular to the longitudinal axis at the bottom of the valley 451 of the first stretch-resistant member 201 is higher than the flatness of the cross section perpendicular to the longitudinal axis at the bottom of the valley 452 of the second stretch-resistant member.

[0129] As shown in Figures 14 and 18, it is preferable that the flatness of the cross section perpendicular to the longitudinal axis at the peak portion 411 of the first stretch-resistance member 201 is higher than the flatness of the cross section perpendicular to the longitudinal axis at the peak portion 412 of the second stretch-resistance member, and it is even more preferable that the flatness of the cross section perpendicular to the longitudinal axis at the valley bottom position of the peak portion 411 of the first stretch-resistance member 201 is higher than the flatness of the cross section perpendicular to the longitudinal axis at the valley bottom position of the peak portion 412 of the second stretch-resistance member.

[0130] As shown in Figures 15 and 19, it is preferable that the flatness of the cross section perpendicular to the longitudinal axis at the boundary between the peak portion 411 and the valley portion 451 of the first stretch resistance member 201 is higher than the flatness of the cross section perpendicular to the longitudinal axis at the boundary between the peak portion 412 and the valley portion 452 of the second stretch resistance member.

[0131] The length 201b of the major axis of the cross-section perpendicular to the longitudinal axis of the first stretch-resistance member 201 may be longer than the length 202b of the major axis of the cross-section perpendicular to the longitudinal axis of the second stretch-resistance member 202. The length 201b may be shorter than the length 202b. The lengths 201b and 202b may be the same.

[0132] The length 201c of the minor axis of the cross-section perpendicular to the longitudinal axis of the first stretch-resistance member 201 may be shorter than the length 202c of the minor axis of the cross-section perpendicular to the longitudinal axis of the second stretch-resistance member 202. The length 201c of the minor axis may be longer than the length 202c. The lengths 201c and 202c of the minor axis may be the same.

[0133] As shown in Figure 11, in system 100, the first in-vivo implantation device 10A may include a first coil 101, a first connection part 751 connected to the proximal end of the first coil 101, and a first pusher 701 connected to the first coil 101 via the first connection part 751. The second in-vivo implantation device 10B may include a second coil 102, a second connection part 752 connected to the proximal end of the second coil 102, and a second pusher 702 connected to the second coil 102 via the second connection part 752. For the configurations of the first connection part 751 and the second connection part 752, and the configurations of the first pusher 701 and the second pusher 702, refer to the descriptions of the connection part 75 and the pusher 70 in "1. In-vivo implantation device," respectively.

[0134] The first in-vivo implantation device 10A may further have a tip 181 positioned at the distal end of the first coil 101. The second in-vivo implantation device 10B may further have a tip 182 positioned at the distal end of the second coil 102. A proximal tip 191 for occluding the proximal end of the first coil 101 may be positioned at the proximal end of the first coil 101. A proximal tip 192 for occluding the proximal end of the second coil 102 may be positioned at the proximal end of the second coil 102. For the configurations of the tip 181, 182 and the proximal tip 191, 192, refer to the descriptions of the tip 18 and proximal tip 19 in "1. In-vivo implantation device," respectively.

[0135] For other details regarding the configuration of system 100, refer to the configurations and methods described in "1. Intra-vivo implantation devices" as appropriate.

[0136] This application claims the benefit of priority based on Japanese Patent Application No. 2024-224227, filed on 19 December 2024. The entire specification of Japanese Patent Application No. 2024-224227, filed on 19 December 2024, is incorporated herein by reference.

[0137] 1: Intraviviparous device 10: Coil 11: Lumen 15: Wire 20: Stretch resistance member 21: First position 21a: First cross section 22: Second position 22a: Second cross section 23: Third position 23a: Third cross section 40: Wave-shaped section 41: Peak 45: Trough 60: Drug 100: System 10A: First intraviviparous device 101: Coil 201: First stretch resistance member 10B: Second intraviviparous device 102: Second coil 202: Second stretch resistance member m: Wave amplitude direction n: Wave propagation direction x: Longitudinal direction of the coil y: Radial direction of the coil z: Circumferential direction of the coil

Claims

1. An in-vivo implant comprising: a coil having a lumen; and a stretch-resistance member disposed in the lumen and having a longitudinal axis direction, wherein a drug is disposed on its surface, wherein the stretch-resistance member has a first cross-sectional shape perpendicular to the longitudinal axis direction at a first position in the longitudinal axis direction and a second cross-sectional shape perpendicular to the longitudinal axis direction at a second position in the longitudinal axis direction.

2. The in-vivo implantation device according to claim 1, wherein the first cross-section has a flattened shape.

3. The in-vivo implantation device according to claim 2, wherein the second cross-section has a flattened shape, and the degree of flatness, which is the value obtained by dividing the length of the major axis of the cross-section perpendicular to the longitudinal axis of the stretch resistance member by the length of the minor axis, is higher for the first cross-section than for the second cross-section.

4. The in-vivo device according to claim 1 or 2, wherein the area of ​​the drug arranged in the first cross-section is greater than the area of ​​the drug arranged in the second cross-section.

5. The in-vivo implantation device according to claim 1 or 2, wherein the first position is located distal to the second position in the longitudinal axis direction.

6. The in-vivo implantation device according to claim 1 or 2, wherein the stretch resistance member has a wave-shaped portion having a peak and a trough in the longitudinal direction of the coil, the trough has a tip region on the trough bottom side and a base region on the peak side, the lengths of which are equal in the amplitude direction of the wave-shaped portion, the tip region of the trough has the first cross-section, and the base region of the trough has the second cross-section.

7. The in-vivo implantation device according to claim 1 or 2, wherein the stretch resistance member has a wave-shaped portion having a peak and a trough in the longitudinal direction of the coil, the peak portion has a tip region on the peak side and a base region on the trough side, the lengths of which are equal in the amplitude direction of the wave-shaped portion, the tip region of the peak portion has the first cross-section, and the base region of the peak portion has the second cross-section.

8. The in-vivo implantation device according to claim 1 or 2, wherein the stretch resistance member has a wave-shaped portion having peaks and valleys in sequence in the longitudinal direction of the coil, and the direction of the major axis of the first cross section is perpendicular to the amplitude direction of the wave-shaped portion and the direction perpendicular to the longitudinal direction of the coil, respectively.

9. An implantation system for an in vivo implant comprising: a first in vivo implant having a lumen; a first stretch-resistance member disposed in the lumen of the first coil and having a longitudinal axis direction, wherein the stretch-resistance member has a drug on its surface; a second in vivo implant having a lumen and having a coil stiffness less than that of the first coil; and a second stretch-resistance member disposed in the lumen of the second coil and having a longitudinal axis direction, wherein the cross-sectional shape of the first stretch-resistance member perpendicular to the longitudinal axis direction and the cross-sectional shape of the second stretch-resistance member perpendicular to the longitudinal axis direction are different.

10. The in-vivo implantation system according to claim 9, wherein the cross-section of the first stretch-resistant member has a flattened shape.

11. The implantation system for an in-vivo implantation device according to claim 10, wherein the cross-section of the second stretch-resisting member has a flattened shape, and the degree of flatness, which is the value obtained by dividing the length of the major axis of the cross-section perpendicular to the longitudinal axis of the stretch-resisting member by the length of the minor axis, is higher for the cross-section of the first stretch-resisting member than for the cross-section of the second stretch-resisting member.

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