In-vivo indwelling tool and method for producing in-vivo indwelling tool

Abstract

Provided is an in-vivo indwelling tool (1) comprising: a coil (10) having a lumen (11); and a linear extension resistance member (20) disposed in the lumen (11), the extension resistance member (20) having a drug (60) disposed on the surface thereof. The extension resistance member (20) has a wavy part (40) having peak parts (41) and valley parts (45) arranged alternately in the longitudinal direction (x) of the coil (10). The drug amount per unit length in the longitudinal direction (x) of the coil (10) at the valley parts (45) is greater than the drug amount per unit length in the longitudinal direction (x) of the coil (10) at the peak parts (41).

Description

Intravascular Implant and Method for Manufacturing the Same

[0001] The present disclosure relates to an intravascular implant for forming an embolism in a blood vessel at a vascular disease site and a method for manufacturing the same.

[0002] Endovascular treatment is one of the treatment methods for vascular lesions such as aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal arteries, and abdominal aneurysms in the head and neck. In endovascular treatment, an embolization coil-containing intravascular implant is placed at the target site, and embolization is used to promote thrombosis to prevent, for example, an aneurysm from rupturing. In embolization, a technique of packing coils into the aneurysm is performed, which includes phases of Framing, Filling, and Finishing. In embolization, coils with different flexibilities are generally selected for each phase. For example, in the Framing phase, it is necessary to create a framework shape inside the aneurysm by making the coil crawl along the inner surface of the aneurysm. On the other hand, in the phases after Filling, a coil with higher flexibility than Framing is selected to fill the coils into the framework formed in Framing. Dozens of coils are used in a single embolization procedure. Patent Document 1 discloses that in an intravascular embolization device having a coil portion and an extension suppression member disposed in the lumen, the extension suppression member has a waveform shape. Patent Document 2 also discloses a vascular embolization device in which a resin wire containing a biochemical active substance is inserted inside a metal coil.

[0003] International Publication No. 2019 / 054066, Japanese Patent Laid-Open No. 11-076249

[0004] The devices described in Patent Documents 1 and 2 had room for improvement from the perspective of drug release efficiency. Therefore, the present disclosure aims to provide an intravascular implant that can efficiently release a drug in the body and a method for manufacturing the intravascular implant.

[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 linear stretch-resistance member disposed in the lumen, wherein a drug is disposed on its surface, the stretch-resistance member having a wave-shaped portion having peaks and valleys in sequence in the longitudinal direction of the coil, and the amount of drug per unit length in the longitudinal direction of the coil at the valleys is greater than the amount of drug per unit length in the longitudinal direction of the coil at the peaks.

[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 valley portion has a tip region on the valley bottom side and a base end region on the peak side, the lengths of which are equal in the amplitude direction of the wave-shaped portion, and the amount of drug per unit length in the longitudinal direction of the coil in the tip region of the valley portion is greater than the amount of drug per unit length in the longitudinal direction of the coil in the base end region of the valley portion. [3] The in-vivo implantation device according to [1] or [2], wherein the peak portion has a tip region on the peak side and a base end region on the valley side, the lengths of which are equal in the amplitude direction of the wave-shaped portion, and the amount of drug per unit length in the longitudinal direction of the coil in the tip region of the peak portion is greater than the amount of drug per unit length in the longitudinal direction of the coil in the base end region of the peak portion. [4] The in-vivo device according to any one of [1] to [3], wherein the trough portion has a tip region on the trough side and a base region on the crest side, the lengths of which are equal in the amplitude direction of the wave-shaped portion, the crest portion has a tip region on the crest 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 amount of drug per unit length in the longitudinal direction of the coil at the base region of the trough portion is greater than the amount of drug per unit length in the longitudinal direction of the coil at the base region of the crest portion. [5] The in-vivo device according to any one of [1] to [4], wherein the stretch resistance member has a first section extending in the longitudinal direction of the coil and a second section arranged parallel to the first section, the crest portion and the trough portion are arranged in the first section and the second section, respectively. [6] The in-vivo implantation device according to [5], wherein the amount of drug per unit length in the longitudinal direction of the coil in the valley of the first section is greater than the amount of drug per unit length in the longitudinal direction of the coil in the valley of the second section. [7] The in-vivo implantation device according to [5] or [6], wherein the amount of drug per unit length in the longitudinal direction of the coil in the peak of the first section is greater than the amount of drug per unit length in the longitudinal direction of the coil in the valley of the second section.[8] The amount of drug per unit length in the longitudinal direction of the coil in the valley portion of the second section is greater than the amount of drug per unit length in the longitudinal direction of the coil in the peak portion of the first section, according to any one of [5] to [7].

[0007] A method for manufacturing an in-vivo implantable device according to an embodiment of the present disclosure that can solve the above problems is as follows: [9] A method for manufacturing an in-vivo implantable device comprising: a step of providing a wave-shaped portion having peaks and valleys to a linear stretch-resistance member; a step of spraying a drug onto the stretch-resistance member from the peak side of the peaks in a direction parallel to the amplitude direction of the wave-shaped portion; and a step of placing the stretch-resistance member to which the drug has been applied into the lumen of a coil.

[0008] According to the above-mentioned in-vivo implantation device, the stretch resistance member is pulled in the direction of stretching due to the extension of the coil. As a result, cracks are more likely to form in the drug in the valleys where more drug is attached than in the peaks. Since the release of the drug is promoted by these cracks, the drug can be released efficiently.

[0009] According to the above-described method for manufacturing an in-vivo implantable device, an in-vivo implantable device can be obtained that has an extension-resistant member on which more drug is attached in the valleys than in the peaks.

[0010] This is a schematic diagram of an in-vivo implantation device according to an embodiment of the present disclosure. This is a cross-sectional view (partially a side view) of the coil of the in-vivo implantation device shown in Figure 1, along the longitudinal direction. This 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. This is a front view of the stretch resistance member shown in Figure 3. This is a side view showing a modified example of the stretch resistance member shown in Figure 3. This is a side view showing a modified example of the stretch resistance member shown in Figure 3. This is a cross-sectional view (partially a side view) showing a modified example of the in-vivo implantation device shown in Figure 2. This is a side view of the stretch resistance member of the in-vivo implantation device shown in Figure 7, viewed from a first direction, showing the peaks and valleys. This is a flowchart of the method for manufacturing an in-vivo implantation device according to an embodiment of the present disclosure. This is a schematic diagram showing step S2 of the method for manufacturing an in-vivo implantation device according to an embodiment of the present disclosure.

[0011] The contents of this disclosure will be described in more detail below based on the embodiments described below. However, the contents of this disclosure are not limited by the embodiments described below, and it is certainly possible to implement the disclosure with appropriate modifications within the scope that is consistent with the spirit of the preceding and following descriptions, and all such modifications are included within the technical scope of this disclosure. In addition, hatching and component reference numerals may be omitted in the drawings for convenience, in which case refer to the specification or other drawings. Furthermore, the dimensions of various components in the drawings may differ from the actual dimensions, as priority is given to helping to understand the features of this disclosure.

[0012] 1. Intra-vivo implantation device The intra-vivo implantation device according to the embodiment of this disclosure comprises a coil having a lumen and a linear stretch-resistant member disposed in the lumen, the stretch-resistant member having a drug on its surface, wherein the stretch-resistant member has a wave-shaped portion having peaks and valleys in sequence in the longitudinal direction of the coil, and the amount of drug per unit length in the longitudinal direction of the coil at the valleys is greater than the amount of drug per unit length in the longitudinal direction of the coil at the peaks. Hereinafter, the intra-vivo implantation device may be simply referred to as the implantation device.

[0013] Examples of the use of implantable devices include embolization to promote thrombosis at target sites such as cerebral aneurysms, head and neck aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal artery aneurysms, and abdominal aneurysms. Among these, implantable devices for cerebral aneurysms are preferred. The shape of the aneurysm can be fusiform or saccular.

[0014] Embolization has three phases: Framing, Filling, and Finishing. The implant can be used in one of these phases, or it can be used across two or three of these phases.

[0015] An in-vivo implantation device according to an embodiment of the present disclosure will be described with reference to Figures 1 to 8. 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) of the coil of the in-vivo implantation device shown in Figure 1, along the longitudinal direction. 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 side view showing a modified example of the stretch resistance member shown in Figure 3. Figure 6 is a side view showing a modified example of the stretch resistance member shown in Figure 3. Figure 7 is a cross-sectional view (partially a side view) showing a modified example of the in-vivo implantation device shown in Figure 2. Figure 8 is a side view of the stretch resistance member of the in-vivo implantation device shown in Figure 7, viewed from a first direction, showing the peaks and valleys. As shown in Figure 2, the implantation device 1 has a coil 10 and a stretch resistance member 20.

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] 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.

[0024] 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.

[0025] 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.

[0026] 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.

[0027] The surface of the coil 10 may have an uneven surface structure if the cross-sections of adjacent wires 15 in the longitudinal direction x of the coil 10 are circular, elliptical, or the like.

[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 linear stretch-resist member 20 is arranged in the lumen 11. A drug 60 is placed 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 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.

[0043] The extension resistance member 20 may be arranged alone in the inner cavity 11, or a plurality of extension resistance members 20 may be arranged.

[0044] The first end side of the extension resistance member 20 may be connected to the distal end portion of the coil 10, for example, the distal end portion of the wire 15. The second end side of the extension resistance member 20 may be connected to the proximal end portion of the coil 10, specifically, the proximal end portion of the wire 15. The second end side of the extension resistance member 20 may be connected to the connecting portion 75 that connects the coil 10 and the pusher 70.

[0045] It is preferable that the folded portion 20a folded in the middle in the longitudinal axis direction of the extension resistance member 20 is connected to the distal end portion or the proximal end portion of the coil 10, and the first end side and the second end side are connected to the proximal end portion or the distal end portion of the coil 10, or the distal end portion of the connecting portion 75. For example, in FIG. 7, the extension resistance member 20 has a folded portion 20a, the folded portion 20a is connected to the distal end portion of the coil 10, and the first end side and the second end side are connected to the connecting portion 75.

[0046] The extension resistance member 20 may be composed of a single member from the first end to the second end, or may be composed of a plurality of members connected to each other in the longitudinal axis direction.

[0047] As a method of connecting the extension resistance member 20 and other members, methods such as welding, soldering, caulking such as crimping, adhesion with an adhesive, physical fixing such as engagement, connection, binding, ligation, etc., or combinations thereof can be mentioned. Here, "connection" shall include both a form in which two elements are directly connected and a form in which two elements are indirectly connected via one or more other elements.

[0048] The extension resistance member 20 may be composed of resin or metal. Examples of the resin constituting the extension 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 the metal constituting the extension resistance member 20 include platinum, gold, rhodium, palladium, rhenium, silver, nickel, titanium, tantalum, tungsten and alloys thereof, and stainless steel.

[0049] 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.

[0050] The shape of the cross-section of the stretch resistance member 20 perpendicular to the longitudinal axis may be circular, oval, polygonal, or a combination thereof.

[0051] As shown in Figures 2 and 3, the stretch resistance member 20 has a wave-shaped portion 40 which has peaks 41 and valleys 45 in sequence in the longitudinal direction x of the coil 10.

[0052] 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 6). (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 5). (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 6, 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 5, 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 5, 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.

[0053] As shown in Figures 7 and 8, if the stretch resistance member 20 has a first section 51 extending in the longitudinal direction x of the coil 10 and a second section 52 arranged parallel to the first section 51, then the peaks 41 and valleys 45 are defined in each of the first section 51 and the second section 52 using the method described above. That is, if the stretch resistance member 20 has a first section 51 and a second section 52, then reference lines are defined in each of the first section 51 and the second section 52. The first reference line BL1, which is the reference line of the first section 51, and the second reference line BL2, which is the reference line of the second section 52, may be parallel to each other or may extend in different directions.

[0054] In the retaining device 1, 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. Therefore, 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. The release of drug 60 is promoted by the cracks, so the release of drug 60 can be carried out efficiently.

[0055] 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.

[0056] 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.

[0057] 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.

[0058] 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.

[0059] 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 5, 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.

[0060] 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.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] The shape of the wave-shaped portion 40 is preferably a plane wave shape. Examples of the shape of the wave-shaped portion 40 include a rectangular wave shape, a triangular wave shape, and a sinusoidal wave shape, but a sinusoidal wave shape is more preferable.

[0066] 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 3, a linear portion 49 is arranged between two wave-shaped portions 40.

[0067] 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).

[0068] 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.

[0069] 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.

[0070] 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.

[0071] As shown in Figure 6, 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 amount of drug per unit length in the longitudinal direction x of the coil 10 in the tip region 45b of 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 base region 45c of the valley portion 45. Here, it is preferable that the amplitude direction m of the wave-shaped portion 40 is perpendicular to the reference line BL and parallel to the radial direction y when viewed from the first direction d1.

[0072] As shown in Figure 6, 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 amount of drug per unit length in the longitudinal direction x of the coil 10 at the tip region 41b of the peak portion 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 portion 41.

[0073] Preferably, the amount of drug per unit length in the longitudinal direction x of the coil 10 at the base end region 45c of the valley portion 45 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 at the base end region 41c of the peak portion 41.

[0074] Preferably, the amount of drug per unit length in the longitudinal direction x of the coil 10 in the tip region 45b of 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 tip region 41b of the peak portion 41.

[0075] 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.

[0076] As shown in Figures 7 and 8, the stretch resistance member 20 has a first section 51 extending in the longitudinal direction x of the coil 10 and a second section 52 arranged parallel to the first section 51, and preferably the peaks and valleys are arranged in the first section 51 and the second section 52, respectively. In this case, it is preferable that the amount of drug per unit length in the longitudinal direction x of the coil 10 at the valley 451 of the first section 51 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 at the peak 411 of the first section 51. Also, it is preferable that the amount of drug per unit length in the longitudinal direction x of the coil 10 at the valley 452 of the second section 52 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 at the peak 412 of the second section 52.

[0077] As shown in Figure 8, when viewing the stretch resistance member 20 from the first direction d1, it is preferable that the first section 51 is positioned above the second section 52.

[0078] With the stretch resistance member 20 positioned in the lumen 11 of the coil 10, the valley portion 451 of the first section 51 and the peak portion 412 of the second section 52 may be in contact with each other, but it is preferable that they are not in contact. It is preferable that the valley portion 451 of the first section 51 and the valley portion 452 of the second section 52 are not in contact. It is preferable that the peak portion 411 of the first section 51 and the peak portion 412 of the second section 52 are not in contact.

[0079] As shown in Figure 8, it is preferable that the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley 451 of the first section 51 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley 452 of the second section 52.

[0080] Although not shown in the diagram, the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley 451 of the first section 51 may be the same as the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley 452 of the second section 52.

[0081] Preferably, the amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 411 of the first section 51 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley portion 452 of the second section 52.

[0082] The amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 411 of the first section 51 may be the same as the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley portion 452 of the second section 52.

[0083] Preferably, the amount of drug per unit length in the longitudinal direction x of the coil 10 in the valley portion 452 of the second section 52 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 411 of the first section 51.

[0084] It is preferable that the amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 411 of the first section 51 is greater than the amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 412 of the second section 52.

[0085] The amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 411 of the first section 51 may be the same as the amount of drug per unit length in the longitudinal direction x of the coil 10 in the peak portion 412 of the second section 52.

[0086] The arrangement of the agent 60 shown in Figures 7 and 8 can be achieved by spraying the agent 60 onto the surface of the stretch-resistance member 20 from the top to the bottom when viewed from the first direction d1, while the first section 51 and the second section 52 of the stretch-resistance member 20 are arranged in parallel.

[0087] 2. Method for Manufacturing an Intra-Visible Device The method for manufacturing an intra-vivable device according to the embodiment of the present disclosure comprises the steps of: imparting a wave-shaped portion having peaks and valleys to a linear stretch-resistant member (step S1); spraying a drug onto the stretch-resistant member from the peak side of the peaks in a direction parallel to the amplitude direction of the wave-shaped portion (step S2); and placing the stretch-resistant member to which the drug has been applied into the lumen of a coil (step S3). According to this manufacturing method, an intra-vivable device can be obtained having a stretch-resistant member in which more drug is attached to the valleys than to the peaks. In such an intra-vivable device, the stretch-resistant member is pulled in the direction of stretching due to the stretching of the coil, so cracks are more likely to form in the drug at the valleys than at the peaks. Then, the release of the drug is promoted by the cracks, so the drug can be released efficiently.

[0088] The method for manufacturing an in-vivo implantable device according to an embodiment of the present disclosure will be explained with reference to Figures 9 to 10. Figure 9 is a flowchart showing the method for manufacturing an in-vivo implantable device according to an embodiment of the present disclosure. Figure 10 is a schematic diagram showing step S2 of the method for manufacturing an in-vivo implantable device according to an embodiment of the present disclosure.

[0089] Step S1 provides a linear stretch-resistant member with a wave-shaped section having peaks and valleys. The stretch-resistant member prepared in Step S1 is preferably linear. The method for providing the wave-shaped section is not particularly limited, but examples include bending the stretch-resistant member by hand while heating it, bending the stretch-resistant member by heating it and fitting it into a mold having a desired shape, bending the stretch-resistant member by heating it, pressing it against a mold having a desired shape and applying vacuum suction (vacuum forming), and bending the stretch-resistant member by passing it between multiple rollers and adjusting the pressure, angle, distance between rollers, etc. (roll bending).

[0090] For details on the structure of the wave-shaped, peak-shaped, and trough-shaped sections, please refer to the explanation in "1. Intra-vivo implantable devices".

[0091] As shown in Figure 10, the drug is sprayed onto the stretch-resist member 20 from the peak side of the peaks in a direction parallel to the amplitude direction m of the wave-shaped portion 40 (step S2). This makes it possible to obtain an in-vivo implant in which the amount of drug per unit length in the longitudinal direction of the coil in the valleys is greater than the amount of drug per unit length in the longitudinal direction of the coil in the peaks. In step S2, it is preferable to spray the drug onto the stretch-resist member 20 from the top to the bottom of the paper in Figures 2 to 8 and Figure 10. In step S2, the drug may also be sprayed onto the stretch-resist member from the peak side of the peaks to the bottom side of the valleys. In step S2, a drug solution containing the drug may be sprayed onto the stretch-resist member using a spray 80 or the like. The drug may also be sprayed while moving the spray 80 over the stretch-resist member. The drug solution preferably contains a solvent that dissolves or disperses the drug. The concentration of the drug in the drug solution is not particularly limited.

[0092] In step S2, it is preferable to spray the drug onto the stretch-resistance member while the stretch-resistance member is held by the holding member. The holding member only needs to have a mechanism that can hold and release the stretch-resistance member, and can hold the stretch-resistance member by methods such as pinching, clamping, gripping, or suction. The holding member can consist of one or more members.

[0093] In step S2, it is preferable that the holding member holds the stretch resistance member at two or more locations. As shown in Figure 2, if the distal end of the stretch resistance member 20 is located on the distal end side of the coil 10 and the proximal end of the stretch resistance member 20 is located on the proximal end side of the coil 10, it is preferable that the holding member holds both the distal end and the proximal end of the stretch resistance member 20, as shown in Figure 10. In Figure 10, the holding member has a first holding portion 81 and a second holding portion 82, where the first holding portion 81 holds one end of the stretch resistance member 20 and the second holding portion 82 holds the other end of the stretch resistance member 20. On the other hand, as shown in Figure 7, when the folded portion 20a of the stretch resistance member 20 is located on the distal end side of the coil 10, and the distal and proximal ends of the stretch resistance member 20 are located on the proximal end side of the coil 10, it is preferable for the holding member to hold the folded portion 20a of the stretch resistance member 20, as well as the distal and proximal ends, respectively.

[0094] In step S2, it is preferable that the holding member holds the stretch resistance member such that the peaks of the peaks face upward in the vertical direction. In step S2, it is preferable that the holding member holds the stretch resistance member such that the troughs face downward in the vertical direction. In step S2, it is preferable that the holding member holds the stretch resistance member such that the direction of propagation n of the wave in the wave-shaped portion of the stretch resistance member is parallel to the horizontal direction. In step S2, it is preferable that the holding member holds the stretch resistance member such that the direction perpendicular to the first direction is parallel to the vertical direction. In step S2, it is preferable that the holding member holds the stretch resistance member such that the amplitude direction m of the wave in the wave-shaped portion of the stretch resistance member is parallel to the vertical direction. In the case of Figure 10, it is preferable that the vertical direction of the paper is the vertical direction and the horizontal direction of the paper is the horizontal direction.

[0095] After step S2, the stretch-resist member may be rotated while evaporating at least a portion of the solvent contained in the drug solution. This facilitates the formation of a drug layer on the outer surface of the stretch-resist member. The evaporation of the solvent may be performed by heating the stretch-resist member sprayed with the drug solution, by placing the stretch-resist member sprayed with the drug solution under reduced pressure, or by selecting a solvent with an appropriate vapor pressure so that the solvent evaporates naturally while the stretch-resist member is rotated. When rotating the stretch-resist member, it is preferable to rotate the stretch-resist member around the axis of a reference line that defines the peaks and valleys. It is preferable to rotate the stretch-resist member with the horizontal direction as the axis of rotation.

[0096] Step S3 involves placing the stretch-resistance member, to which the drug has been applied, into the lumen of the coil. In Step S3, it is preferable that the stretch-resistance member is placed in the lumen of the coil such that the corrugated portion of the stretch-resistance member does not come into contact with other members. The configuration of the coil used in Step S3 can be found in the description of the coil (primary coil) in "1. Intravascular Implantation Device".

[0097] Although not shown in the figures, the method for manufacturing an in-vivo implantable device may further include the step of preparing a pusher and a connecting part, and connecting the pusher and the connecting part (step S4).

[0098] For details on the structure of the pusher and connection parts, please refer to the description of the pusher 70 and connection part 75 in "1. Intravivo Devices".

[0099] In step S4, it is preferable to connect the proximal end of the coil to the distal end of the connection part. In step S4, it is preferable to connect the proximal end of the connection part to the distal end of the pusher.

[0100] In step S4, methods for connecting the coil to the connector, or the connector to the pusher, include methods such as welding, crimping, bonding with adhesive, engagement, linking, binding, ligation, or other physical fixing, 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.

[0101] When carrying out the above manufacturing method, the configuration and method described in "1. Intravivo Devices" can be referred to as appropriate.

[0102] This application claims the benefit of priority based on Japanese Patent Application No. 2024-224226, filed on 19 December 2024. The entire specification of Japanese Patent Application No. 2024-224226, filed on 19 December 2024, is incorporated herein by reference.

[0103] 1: Intravivo device 10: Coil 11: Lumen 15: Wire 20: Stretch resistance member 20a: Folded section 40: Wave-shaped section 41: Peak section 41a: Uppermost end 41b: Tip region 41c: Base region 45: Valley section 45a: Uppermost end 45b: Tip region 45c: Base region 51: First section 52: Second section 60: Drug 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 linear stretch-resist member disposed in the lumen, wherein a drug is disposed on its surface, the stretch-resist member having a wave-shaped portion with crests and valleys in sequence in the longitudinal direction of the coil, and the amount of drug per unit length in the longitudinal direction of the coil at the valleys is greater than the amount of drug per unit length in the longitudinal direction of the coil at the crests.

2. The in-vivo implantation device according to claim 1, wherein the valley portion has a tip region on the valley 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, and the amount of drug per unit length in the longitudinal direction of the coil in the tip region of the valley portion is greater than the amount of drug per unit length in the longitudinal direction of the coil in the base region of the valley portion.

3. The in-vivo device according to claim 1, wherein the peak portion has a peak-side tip region and a trough-side base region, the lengths of which are equal in the amplitude direction of the wave-shaped portion, and the amount of drug per unit length in the longitudinal direction of the coil in the peak-side tip region is greater than the amount of drug per unit length in the longitudinal direction of the coil in the base region of the peak.

4. The in-vivo device according to claim 1, wherein the trough portion has a tip region on the trough 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 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 amount of drug per unit length in the longitudinal direction of the coil in the base region of the trough portion is greater than the amount of drug per unit length in the longitudinal direction of the coil in the base region of the peak portion.

5. The in-vivo implantation device according to claim 1 or 2, wherein the stretch resistance member has a first section extending in the longitudinal direction of the coil and a second section arranged parallel to the first section, and the peaks and valleys are arranged in the first section and the second section, respectively.

6. The in-vivo implantation device according to claim 5, wherein the amount of drug per unit length in the longitudinal direction of the coil in the valley of the first section is greater than the amount of drug per unit length in the longitudinal direction of the coil in the valley of the second section.

7. The in-vivo implantation device according to claim 5, wherein the amount of drug per unit length in the longitudinal direction of the coil in the peak portion of the first section is greater than the amount of drug per unit length in the longitudinal direction of the coil in the valley portion of the second section.

8. The in-vivo implantation device according to claim 5, wherein the amount of drug per unit length in the longitudinal direction of the coil in the valley portion of the second section is greater than the amount of drug per unit length in the longitudinal direction of the coil in the peak portion of the first section.

9. A method for manufacturing an in-vivo device, comprising the steps of: providing a linear stretch-resistance member with a wave-shaped portion having peaks and valleys; spraying a drug onto the stretch-resistance member from the peak side of the peaks in a direction parallel to the amplitude direction of the wave-shaped portion; and placing the stretch-resistance member to which the drug has been applied into the lumen of a coil.

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