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

Abstract

Provided is an in-vivo indwelling tool (1) having a coil (10) in which a drug (60) is disposed on the surface thereof, wherein the amount of the drug per coil unit length on the outer circumferential surface (12) of the coil (10) is less than the amount of the drug per coil unit length on the inner circumferential surface (13) of the coil (10).

Description

Intravital indwelling device and method for manufacturing the same

[0001] The present invention relates to an in-vivo indwelling device for embolizing a blood vessel in a vascular diseased area and a method for manufacturing the in-vivo indwelling device.

[0002] Endovascular treatment is one of the treatments for vascular lesions, such as head and neck aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, and renal artery and abdominal aneurysms. In endovascular treatment, embolization is used, in which an in-vivo device containing embolization coils is placed at the target site to promote thrombosis and prevent, for example, aneurysm rupture. Embolization involves the procedure of filling the aneurysm with coils, which consists of the framing, filling, and finishing phases. In embolization, coils with different flexibility are generally selected for each phase. For example, in the framing phase, it is necessary to form a framework within the aneurysm by running coils along the inner surface of the aneurysm. On the other hand, in the phases after filling, coils are filled into the framework formed during framing, so coils with greater flexibility than those used during framing are selected. Several to several dozen coils are used in a single embolization procedure. Patent Documents 1 to 6 disclose in-vivo indwelling devices in which a coil holds a drug.

[0003] US Patent Application Publication No. 2007 / 0299461 Specification JP-A-2005-513081 JP-A-2013-537046 JP-A-2015-195978 JP-A-2007-534358 JP-A-2008-284391

[0004] From the viewpoint of sustained drug release, it would be beneficial to provide a novel in-vivo indwelling device and a method for manufacturing the same. Therefore, an object of the present invention is to provide an in-vivo indwelling device and a method for manufacturing the same that facilitates increased sustained drug release and makes it easier to efficiently deliver the drug required for treatment to the treatment site inside the body.

[0005] The in-vivo indwelling device according to the embodiment of the present invention that can solve the above problems is as follows: [1] An in-vivo indwelling device having a coil on the surface of which a drug is disposed, wherein the amount of drug per unit length on the outer circumferential surface of the coil is less than the amount of drug per unit length on the inner circumferential surface of the coil.

[0006] Furthermore, the in-vivo indwelling device according to the embodiment is preferably any one of the following [2] to

[10] . [2] The in-vivo indwelling device according to [1], further comprising a stretch resisting member disposed in the lumen of the coil, wherein a drug is disposed on the surface of the stretch resisting member. [3] The in-vivo indwelling device according to [1] or [2], further comprising a connection part disposed in the lumen of the coil and connected to the proximal end of the coil, and a pusher connected to the coil via the connection part, wherein the drug is disposed distally of the distal end of the connection part in the longitudinal axis direction of the coil. [4] The in-vivo indwelling device according to [3], wherein the coil has a first portion where the coil and the connection part overlap in the longitudinal axis direction of the coil, wherein no drug is disposed on the surface of the coil in the first portion. [5] The in-vivo indwelling device according to [3], wherein the coil has a first portion where the coil and the connecting portion overlap in the longitudinal axis direction of the coil, and a second portion from the distal end of the coil to the distal end of the first portion, and the amount of drug per unit coil length on the surface of the coil in the first portion is less than the amount of drug per unit coil length on the surface of the coil in the second portion. [6] The in-vivo indwelling device according to [5], wherein when the first portion is divided into two equal parts in the longitudinal axis direction of the coil into a distal first portion and a proximal first portion, the amount of drug per unit coil length on the surface of the coil in the proximal first portion is less than the amount of drug per unit coil length on the surface of the coil in the distal first portion. [7] The in-vivo indwelling device according to [5], wherein when the first portion is divided into two equal parts in the longitudinal axis direction of the coil into a distal first portion and a proximal first portion, the amount of drug per unit area of ​​the coil on the surface of the coil in the proximal first portion is greater than the amount of drug per unit area of ​​the coil on the surface of the coil in the distal first portion. [8] The coil hardness of the coil is 5.0 × 10 －９[9] The in-vivo indwelling device according to any one of [1] to [7], wherein the drug is encapsulated in a capsule containing a biodegradable material.

[10] The in-vivo indwelling device according to any one of [1] to [9], wherein the drug has at least one of an anti-inflammatory effect, an antioxidant effect, a hypotensive effect, and a shear stress sensing inhibitory effect.

[0007] The manufacturing method of an in-vivo indwelling device according to the first embodiment of the present invention, which has been able to solve the above problems, is as follows:

[11] A manufacturing method of an in-vivo indwelling device, comprising the steps of: preparing a wire and a drug; applying the drug to only a partial section in the circumferential direction of the wire; and winding the drug-applied wire to form a first coil.

[0008] Furthermore, the manufacturing method of the in-vivo indwelling device according to the first embodiment is preferably the following

[12] :

[12] The manufacturing method of the in-vivo indwelling device according to

[11] , wherein in the step of winding the drug-impregnated wire to form a first coil, the drug-impregnated wire is wound so that the section of the drug-impregnated wire to which the drug is impregnated is located on the inner circumferential side of the first coil.

[0009] A method for manufacturing an in-vivo indwelling device according to a second embodiment of the present invention that can solve the above problems is as follows:

[13] A method for manufacturing an in-vivo indwelling device, comprising the steps of: preparing a wire and a drug; applying a first predetermined amount of drug to a first section in the circumferential direction of the wire, and applying a second predetermined amount of drug, which is smaller than the first predetermined amount, to a second section in the circumferential direction of the wire that is located at a different position from the first section; and winding the wire to which the drug has been applied to form a first coil.

[0010] Furthermore, the manufacturing method of the in-vivo indwelling device according to the second embodiment is preferably the following

[14] :

[14] The manufacturing method of the in-vivo indwelling device according to

[13] , wherein in the step of winding the drug-impregnated wire to form a first coil, the drug-impregnated wire is wound so that the first section is located on the inner periphery of the first coil and the second section is located on the outer periphery of the first coil.

[0011] Furthermore, the method for manufacturing the in-vivo indwelling device according to the first or second embodiment is preferably the following

[15] :

[15] The method for manufacturing the in-vivo indwelling device according to any one of

[11] to

[14] , further comprising a step of reducing the outer diameter of the first coil.

[0012] A manufacturing method for an in-vivo indwelling device according to a third embodiment of the present invention, which has been able to solve the above problems, is as follows:

[16] A manufacturing method for an in-vivo indwelling device, comprising the steps of: preparing a second coil to which no drug has been applied and a storage section in which a drug has been stored; immersing the second coil in the storage section to apply a drug to the surface of the second coil; and removing only a portion of the drug applied to the outer peripheral surface of the second coil.

[0013] Furthermore, the manufacturing method of the in-vivo indwelling device according to the third embodiment is preferably the following

[17] :

[17] The manufacturing method of the in-vivo indwelling device according to

[16] , further comprising a step of reducing the outer diameter of the second coil.

[0014] The in-vivo indwelling device described above facilitates enhanced sustained drug release and makes it easier to efficiently deliver the drug required for treatment to the treatment site inside the body.

[0015] Furthermore, according to the manufacturing methods of the in-vivo indwelling device according to the first to third embodiments, it is possible to obtain an in-vivo indwelling device that can easily improve the sustained drug release and can easily efficiently deliver the drug required for treatment to the treatment site inside the body.

[0016] FIG. 1 is a schematic diagram of an in-vivo indwelling device according to an embodiment of the present invention; FIG. 2 is a cross-sectional view (partially a side view) taken along the longitudinal axis direction of the coil of the in-vivo indwelling device shown in FIG. 1; FIG. 3 is an enlarged cross-sectional view (partially a side view) of the periphery of the proximal end of the coil of the in-vivo indwelling device shown in FIG. 2; FIG. 4 is a schematic cross-sectional view taken at an arbitrary position in the longitudinal axis direction of the coil of the in-vivo indwelling device shown in FIG. 2; FIG. 5 is a cross-sectional view (partially a side view) showing a modification of the stretch resistance member shown in FIG. 2, a cross-sectional view perpendicular to the longitudinal axis direction of the stretch resistance member; FIG. 6 is a cross-sectional view (partially a side view) showing a modification of the in-vivo indwelling device shown in FIG. 3; FIG. 7 is a cross-sectional view (partially a side view) showing another modification of the in-vivo indwelling device shown in FIG. 3; FIG. 8 is a cross-sectional view (partially a side view) showing yet another modification of the in-vivo indwelling device shown in FIG. 3; FIG. 9 is a cross-sectional view (partially a side view) showing yet another modification of the in-vivo indwelling device shown in FIG. 3; 19 is a cross-sectional view (partially a side view) showing yet another modified example of the biological indwelling device shown in FIG. 3. FIG. 19 is a cross-sectional view (partially a side view) showing yet another modified example of the biological indwelling device shown in FIG. 3. FIG. 19 is a flowchart showing a method for manufacturing an biological indwelling device according to the first embodiment of the present invention. FIG. 19 is a cross-sectional view showing an example of applying a drug to a wire in step S2 of the manufacturing method shown in FIG. 14. FIG. 20 is a perspective view showing an example of applying a drug to a wire in step S2 of the manufacturing method shown in FIG. 14. FIG. 20 is a cross-sectional view showing an example of forming a first coil in step S3 of the manufacturing method shown in FIG. 14. FIG. 21 is a flowchart showing a modification of the manufacturing method shown in FIG. 14. FIG. 22 is a flowchart showing a method for manufacturing an biological indwelling device according to a second embodiment of the present invention. FIG. 23 is a cross-sectional view showing an example of applying a drug to a wire in step S12 of the manufacturing method shown in FIG. 19. FIG. 24 is a perspective view showing an example of applying a drug to a wire in step S12 of the manufacturing method shown in FIG. 19. FIG. 25 is a cross-sectional view showing an example of forming a first coil in step S13 of the manufacturing method shown in FIG. 19. FIG. 26 is a flowchart showing a modification of the manufacturing method shown in FIG. 19. FIG. 27 is a flowchart showing a method for manufacturing an biological indwelling device according to a third embodiment of the present invention. FIG. 28 is a flowchart showing a modification of the manufacturing method shown in FIG.

[0017] The present invention will be described in more detail below based on the following embodiments. However, the present invention is not limited to the following embodiments, and can be implemented with appropriate modifications within the scope of the above and below-described purposes, and all such modifications are included within the technical scope of the present invention. For convenience, hatching and component symbols may be omitted in the drawings. In such cases, reference should be made to the specification and other drawings. The dimensions of various components in the drawings may differ from their actual dimensions, as priority is given to helping understand the features of the present invention.

[0018] 1. In-vivo indwelling devices Hereinafter, in-vivo indwelling devices may be simply referred to as indwelling devices. Examples of uses for indwelling devices include embolization, which promotes thrombosis at target sites such as cerebral aneurysms, head and neck aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal arteries, and abdominal aneurysms. Of these, it is preferable that the indwelling device be a device for cerebral aneurysms. Examples of the shape of the aneurysm include fusiform and saccular.

[0019] An in-vivo indwelling device according to an embodiment of the present invention is an in-vivo indwelling device having a coil with a drug disposed on its surface, wherein the amount of drug per unit length on the outer circumferential surface of the coil is less than the amount of drug per unit length on the inner circumferential surface of the coil. This in-vivo indwelling device facilitates increased sustained drug release and facilitates efficient delivery of the drug required for treatment to a treatment site within the body. Specifically, disposing the drug on the inner circumferential surface of the coil facilitates increased sustained drug release. Furthermore, disposing a larger amount of drug on the inner circumferential surface than on the outer circumferential surface facilitates reduced frictional resistance during delivery to the treatment site and reduces the amount of drug that may fall off during delivery, facilitating efficient delivery of the drug required for treatment to the treatment site.

[0020] Embolization has three phases: framing, filling, and finishing. The placement device can be used in any one of the phases, or in any two or three of the phases.

[0021] An in-vivo indwelling device according to an embodiment of the present invention will be described with reference to FIGS. 1 to 13. FIG. 1 is a schematic diagram of an in-vivo indwelling device according to an embodiment of the present invention. FIG. 2 is a cross-sectional view (partially a side view) taken along the longitudinal axis of the coil of the in-vivo indwelling device shown in FIG. 1. FIG. 3 is an enlarged cross-sectional view (partially a side view) of the periphery of the proximal end of the coil of the in-vivo indwelling device shown in FIG. 2. FIG. 4 is a schematic cross-sectional view of the coil of the in-vivo indwelling device shown in FIG. 2 at an arbitrary position along the longitudinal axis. FIG. 5 is a cross-sectional view showing a modification of the stretch resistance member shown in FIG. 2, taken perpendicular to the longitudinal axis of the stretch resistance member. FIGS. 6 to 13 are cross-sectional views (partially a side view) showing a modification of the in-vivo indwelling device shown in FIG. 3. As shown in FIGS. 1 to 3 and 6 to 13, the indwelling device 1 includes a coil 10 and a drug 60.

[0022] As can be seen from FIG. 2 , the coil 10 preferably has a longitudinal axis direction x, a radial direction y, and a circumferential direction z. The coil 10 preferably has a distal end 10a and a proximal end 10b in the longitudinal axis direction x. The proximal side of the coil 10 refers to the direction toward the user or surgeon with respect to the longitudinal axis 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. Note that in FIG. 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, the inward direction refers to the direction toward the center of the longitudinal axis of the coil 10, and the outward direction refers to the direction extending radially from the center of the longitudinal axis opposite to the inward direction. The circumferential direction z of the coil 10 refers to the direction around the longitudinal axis.

[0023] In this specification, unless otherwise specified, the term "coil 10" refers to the configuration in the state of a primary coil. A primary coil further formed into a spiral or three-dimensional shape is sometimes called a secondary coil. Preferably, the primary coil 10 shown in FIG. 2 is formed into a secondary coil as shown in FIG. 1 by forming the coil 10. In FIG. 1, the three-dimensional secondary coil shape is formed by winding the primary coil. The coil 10 of the indwelling device 1 is inserted into the lumen of a delivery catheter in the state of a linear primary coil as shown in FIG. 2 and delivered to the target site. When the primary coil is pushed out of the catheter, it is placed in the aneurysm in a state where it is expanded into a three-dimensional shape as shown in FIG. 1 or in a state where it conforms to the shape of the aneurysm.

[0024] 2 and 3, the coil 10 has an outer circumferential surface 12 and an inner circumferential surface 13. The surface of the coil 10 includes the outer circumferential surface 12 and the inner circumferential surface 13. The coil 10 preferably has an inner cavity 11 extending in the longitudinal axis direction x. The outer circumferential surface 12 of the coil 10 faces the outside of the coil 10, i.e., the outside in the radial direction y, and the inner circumferential surface 13 of the coil 10 faces the inner cavity 11. A stretch resistance member 40, which will be described later, is preferably disposed in the inner cavity 11.

[0025] 2 and 3, a drug 60 is disposed on the surface of the coil 10. The drug 60 is preferably held on the surface of the coil 10 as a drug layer. In particular, the drug 60 may be held on the surface of the coil 10 in a form encapsulated in a microcapsule or the like, or the drug 60 encapsulated in a capsule may be held on the surface of the coil 10 in the form of a layer.

[0026] The drug 60 may be an active ingredient (drug substance) alone or a mixture with other additives. Examples of preferred additives include base materials, plasticizers, stabilizers, surfactants, etc. In this specification, the term "amount of drug" refers to the weight of the drug. When the drug is a mixture containing additives, the term "amount of drug" refers to the weight of the mixture. Since the amount of drug is proportional to the thickness of the drug layer, the amount of drug on the outer peripheral surface 12 and the inner peripheral surface 13 can be determined from the thickness of the drug layer. The drug and the specific configuration for disposing the drug on the surface of the coil 10 will be described later.

[0027] 1 to 3, the coil 10 is preferably configured by spirally winding one or more wires 31. Examples of the wires 31 include solid wires, twisted wires, and coiled wires, among which solid wires are preferred. It is also preferred that the wires 31 are not coil wires.

[0028] The wire 31 is preferably biocompatible and flexible. Examples of materials constituting the wire 31 include metal materials such as platinum, gold, titanium, tungsten, alloys thereof, stainless steel, and combinations thereof. Of these, the wire 31 is more preferably made of a platinum-tungsten alloy.

[0029] The wire 31 has a longitudinal axis direction and a distal end and a proximal end in the longitudinal axis direction of the wire 31. The wire 31 may be composed of a single linear member from the distal end to the proximal end, or may be composed of multiple linear members connected to each other in the longitudinal axis direction. The cross-sectional shape of the wire 31 perpendicular to the longitudinal axis direction may be circular, elliptical, polygonal, or a combination thereof. The cross-sectional shape of the wire 31 perpendicular to the longitudinal axis direction may be the same throughout the entire longitudinal axis direction of the wire 31, or may vary depending on the position in the longitudinal axis direction.

[0030] The outer diameter of the wire 31 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.

[0031] The outer diameter of the wire 31 may be the same in the longitudinal direction of the wire 31, or may be different depending on the position in the longitudinal direction of the wire 31. When the cross section of the wire 31 is not circular, the outer diameter of the wire 31 refers to the diameter equivalent to a circle.

[0032] 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 axis direction x may be single-layered, and the remaining portion may be multi-layered.

[0033] The density of the coil 10, i.e., the winding spacing, is not particularly limited, and can be close winding, pitch winding, or a combination of these. In the coil 10, adjacent wire rods 31 may be in contact with each other in the longitudinal axis direction x. In the coil 10, adjacent wire rods 31 may be in contact with each other only in a portion of the longitudinal axis direction x, or adjacent wire rods 31 may be in contact with each other over the entire longitudinal axis direction x. Furthermore, in the coil 10, adjacent wire rods 31 may not be in contact with each other in the longitudinal axis direction x. A non-contact state refers to a state in which adjacent wire rods 31 are spaced apart in the longitudinal axis direction x of the coil 10.

[0034] The cross-sectional shape of the coil 10 perpendicular to the longitudinal axis direction x may be a circle, an oval, a polygon, or a combination thereof. The oval shape includes an ellipse, an egg, and a rounded rectangle. The same applies to the following description.

[0035] The maximum and minimum outer diameters of the coil 10 are not particularly limited and can be selected appropriately depending on the phase of the procedure, but may be, for example, 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.

[0036] The outer diameter and / or inner diameter of the coil 10 may be the same in the longitudinal axis direction x of the coil 10, or may be different depending on the position in the longitudinal axis direction x of the coil 10. If the cross section of the coil 10 is not circular, the outer diameter of the coil 10 refers to the circle-equivalent diameter. If the cross section of the lumen of the coil 10 is not circular, the inner diameter of the coil 10 refers to the circle-equivalent diameter.

[0037] The coil 10 may have a constant outer diameter in the longitudinal axis direction x. A constant outer diameter means that the outer diameter of the coil 10 is substantially constant throughout the entire longitudinal axis direction x of the coil 10, and includes cases where the change in the outer diameter of the coil 10 is within a range of ±5% throughout the entire longitudinal axis direction x.

[0038] As shown in Figure 2, in the indwelling device 1, the amount of drug (mg / mm) per unit length of the coil on the outer circumferential surface 12 of the coil 10 is less than the amount of drug (mg / mm) per unit length of the coil on the inner circumferential surface 13 of the coil 10. Disposing the drug 60 on the inner circumferential surface 13 of the coil 10 facilitates improving sustained drug release. Furthermore, disposing more drug 60 on the inner circumferential surface 13 than on the outer circumferential surface 12 facilitates reducing frictional resistance during delivery to the treatment site and reduces the amount of drug that may fall off during delivery, making it easier to efficiently apply the drug 60 required for treatment to the treatment site.

[0039] In the longitudinal axis direction x of the coil 10, the drug 60 may be disposed on only a portion of the outer peripheral surface 12, or may be disposed on the entire outer peripheral surface 12. In the circumferential direction z of the coil 10, the drug 60 may be disposed on only a portion of the outer peripheral surface 12, or may be disposed on the entire outer peripheral surface 12.

[0040] In the longitudinal axis direction x of the coil 10, the drug 60 may be disposed on only a portion of the inner circumferential surface 13, or may be disposed on the entire inner circumferential surface 13. In the circumferential direction z of the coil 10, the drug 60 may be disposed on only a portion of the inner circumferential surface 13, or may be disposed on the entire inner circumferential surface 13.

[0041] In this specification, when comparing the amount of drug or the thickness of the drug layer disposed on one portion of the surface of coil 10 with another portion (e.g., outer peripheral surface 12 and inner peripheral surface 13, first portion 21 and second portion 25 described below, distal first portion 22 and proximal first portion 23, etc.), the drug amount or drug layer thickness is measured in the same manner for one portion and another portion. Note that even if the surface of coil 10 is covered with another member, the length or area of ​​the covered portion is also treated as the length or area to be compared when calculating the drug amount per unit length or unit area of ​​the coil.

[0042] The amount of drug per unit length of the coil (mg / mm) or per unit area of ​​the coil (mg / mm) on one part of the surface of the coil 10 and the other part ２) can be measured using various elemental analyzers, for example, spectrophotometers such as Raman spectrophotometers and near-infrared spectrophotometers, and X-ray fluorescence analyzers. The amount of drug per unit length of the coil or per unit area of ​​the coil in one portion and another portion of the surface of the coil 10 may be determined by extracting the drug disposed in one portion or another portion of the coil 10 with a solvent and analyzing the concentration. The type of solvent is not particularly limited, and examples that can be used include ethanol, methanol, acetone, ethyl acetate, acetonitrile, N,N-dimethylacetamide, propanol, chloroform, and benzyl alcohol.

[0043] The amount of drug per unit length of the coil on the outer surface 12 of the coil 10 may be 0.9 times or less, 0.8 times or less, 0.7 times or less, or 0.1 times or more, 0.2 times or more, or 0.3 times or more, of the amount of drug per unit length of the coil on the inner surface 13 of the coil 10.

[0044] 2 and 3, a drug layer may be disposed on each of outer peripheral surface 12 and inner peripheral surface 13. It is preferable that the average thickness Ti of the drug layer on inner peripheral surface 13 is greater than the average thickness To of the drug layer on outer peripheral surface 12.

[0045] Since the amount of drug is proportional to the thickness of the drug layer, the amount of drug on the outer peripheral surface 12 and the inner peripheral surface 13 can be determined from the thickness of the drug layer. The drug layer thickness refers to the length of the layer of drug 60 in the radial direction y of the coil 10. The average thickness of the drug layer on the outer peripheral surface 12 or the inner peripheral surface 13 can be easily determined by measuring the average thickness of the drug layer at multiple representative points along the longitudinal axis direction x of the coil 10. For example, ten positions P1 to P10 (not shown) are determined at equal intervals along the longitudinal axis direction x of the coil 10, and a cross section of the coil 10 perpendicular to the longitudinal axis direction x is observed at each of the positions P1 to P10. A microscope such as an optical microscope can be used for observation. On the vertical cross section at each of the positions P1 to P10, eight points are determined at equal intervals along the circumferential direction z. For example, Figure 4 shows a schematic vertical cross section of the coil 10 at an arbitrary position P1, in which eight points P11 to P18 are determined at equal intervals along the circumferential direction z. The thickness To of the drug layer on the outer peripheral surface 12 will now be described. The thickness of the drug layer on the outer peripheral surface 12 is measured at eight points P11 to P18 on the vertical cross section at position P1, and the average value of the measurement results at the eight points P11 to P18 is calculated. Similarly, eight measurements are performed at the remaining positions P2 to P10, and the average value of the eight points is calculated. The average value of the drug layer thickness measurements at the ten positions P1 to P10 can be used as the average thickness To of the drug layer on the outer peripheral surface 12. The average thickness Ti of the drug layer on the inner peripheral surface 13 can be calculated in the same manner as for the outer peripheral surface 12. The ten positions P1 to P10 are selected to be positions arranged around the entire circumference of the coil 10. The eight points equally spaced in the circumferential direction z can be points spaced 45° apart out of 360° of the circumferential direction z of the coil 10. The eight points spaced 45° apart can be determined as the points where a line intersects with the outer edge of coil 10 when a line is drawn connecting the centroid C of the outer edge of coil 10 to the outer edge of coil 10 so that the angle between the lines is 45° in a cross section perpendicular to the longitudinal axis direction x. The "average thickness of the drug layer" can be determined in a similar manner in the following explanations.

[0046] The thickness of the drug layer on outer peripheral surface 12 may vary depending on the position in the longitudinal axis direction x, or may be the same in the longitudinal axis direction x. The thickness of the drug layer on outer peripheral surface 12 may vary depending on the position in the circumferential direction z, or may be the same in the circumferential direction z.

[0047] The thickness of the drug layer on inner circumferential surface 13 may vary depending on the position in the longitudinal axis direction x, or may be the same in the longitudinal axis direction x. The thickness of the drug layer on inner circumferential surface 13 may vary depending on the position in the circumferential direction z, or may be the same in the circumferential direction z.

[0048] The type of drug 60 (active ingredient) disposed on the outer peripheral surface 12 and the type of drug 60 (active ingredient) disposed on the inner peripheral surface 13 may be the same or different.

[0049] When the coil 10 is divided into two equal parts, a distal part and a proximal part, in the longitudinal axis direction x, the amount of drug disposed in the distal part of the coil 10 may be greater than the amount of drug disposed in the proximal part. This allows the amount of drug 60 required for treatment to be applied to the aneurysm, and the proximal part has greater flexibility than the distal part, making it easier to operate.

[0050] The drug 60 may not be disposed in the proximal portion of the coil 10. This further increases the flexibility of the proximal portion, resulting in improved operability.

[0051] The type of drug 60 (drug substance) placed in the distal portion and the type of drug 60 (drug substance) placed in the proximal portion may be the same or different.

[0052] As shown in FIG. 2 , the indwelling device 1 preferably includes a stretch resistance member 40 disposed in the lumen 11 of the coil 10. The stretch resistance member 40 prevents the coil 10 from stretching in the longitudinal axis direction x during operation. The stretch resistance member 40 may be a long member made of a solid wire or a stranded wire. The stretch resistance member 40 has a longitudinal axis direction and has a first end and a second end in the longitudinal axis direction. The stretch resistance member 40 may be composed of a single layer or multiple layers in the radial direction perpendicular to the longitudinal axis direction. The stretch resistance member 40 may have an inner layer made of a stranded wire composed of multiple wires and an outer layer containing a resin composition disposed outside the inner layer. Only one stretch resistance member 40 may be disposed in the lumen 11, or multiple stretch resistance members 40 may be disposed.

[0053] The stretch resisting member 40 may be made of resin or metal. Examples of resins that make up the stretch resisting member 40 include polyester resins such as polyethylene terephthalate, polyamide resins such as nylon, and polyolefin resins such as polyethylene and polypropylene. Using resin increases flexibility, improving the delivery performance of the indwelling device 1. Furthermore, using a resin stretch resisting member 40 can prevent breakage due to metal fatigue during delivery. By making the length of the stretch resisting member 40 longer than the length of the coil 10 or using a stretchable material for the stretch resisting member 40, tension caused by linear stretching of the end of the coil 10 due to insufficient length of the stretch resisting member 40 when the coil 10 is placed within the aneurysm can be alleviated. Examples of metals that make up the stretch resisting member 40 include platinum, gold, rhodium, palladium, rhenium, silver, nickel, titanium, tantalum, tungsten, alloys thereof, and stainless steel.

[0054] The stretch resistance member 40 may be made of a material different from that of the wire 31 that makes up the coil 10. For example, the coil 10 may be made of a platinum-tungsten alloy, and the stretch resistance member 40 may be made of polypropylene resin.

[0055] The shape of the stretch resistance member 40 may be a circle, an oval, a polygon, or a combination thereof in cross section perpendicular to its longitudinal axis.

[0056] To facilitate placement of the stretch resistance member 40 in the lumen 11, the outer diameter of the stretch resistance member 40 is preferably smaller than half, and more preferably equal to or smaller than one-third, of the inner diameter of the coil 10. To prevent breakage of the stretch resistance member 40, the outer diameter of the stretch resistance member 40 is preferably equal to or larger than one-fifteenth, and more preferably equal to or larger than one-tenth, of the inner diameter of the coil 10.

[0057] The stretch resistant member 40 can be straight, wavy, spiral, or a combination thereof.

[0058] The first end of the stretch resistance member 40 may be connected to the distal end of the coil 10, specifically the distal end of the wire 31 that constitutes the coil 10. The second end of the stretch resistance member 40 may be connected to the proximal end of the coil 10, specifically the proximal end of the wire 31. The second end of the stretch resistance member 40 may be connected to a connection part 50 (described below) that connects the coil 10 and the pusher 55. The stretch resistance member 40 may be disposed in the lumen 11 in a state where it is folded back midway along the longitudinal axis of the stretch resistance member 40. In this case, it is preferable that the folded back part 41 of the stretch resistance member 40 is connected to the distal or proximal end of the coil 10, and the first and second ends are connected to the proximal or distal end of the coil 10 or the distal end of the connection part 50. For example, in Figure 2, the elongation resistance member 40 has a folded portion 41 folded back halfway in the longitudinal axis direction, and the folded portion 41 is connected to the distal end of the coil 10, and the first end side and the second end side are connected to the connection portion 50.

[0059] The stretch resistant member 40 may be connected to another member by welding, crimping, or other crimping methods, or by physical fastening, such as by adhesive bonding, engaging, connecting, fastening, or ligating, or by any combination thereof. Here, "connection" includes both a direct connection between two elements and an indirect connection between two elements via one or more other elements.

[0060] As shown in FIG. 5 , it is preferable that the drug 60 be disposed on the surface of the stretch resisting member 40. This facilitates efficient delivery of the drug 60 required for treatment to the treatment site within the body. The drug 60 may be disposed on only a portion of the stretch resisting member 40 in the longitudinal direction, or may be disposed over the entire stretch resisting member 40 in the longitudinal direction. As with the coil 10, the drug 60 may be directly attached to the surface of the stretch resisting member 40, or may be indirectly attached to the surface of the stretch resisting member 40 via a bioadhesive. As with the coil 10, the drug 60 encapsulated in a capsule may be directly attached to the surface of the stretch resisting member 40, or may be indirectly attached to the surface of the stretch resisting member 40 via a bioadhesive. For information on the type of bioadhesive, please refer to the description of the type of bioadhesive attached to the coil 10. For information on the structure of the capsule, please refer to the description of the structure of the capsule attached to the coil 10.

[0061] 1 and 2, the coil 10 may have a head portion 35 at its distal end. The head portion 35 covers a portion of the wire 31 to prevent the distal end of the wire 31 from directly contacting the inner wall surface of the living body. The head portion 35 may or may not be in contact with the stretch resistance member 40.

[0062] The shape of the head portion 35 is not particularly limited, but may be, for example, a hemisphere, an oval hemisphere, a cylinder, or a polygonal pillar.

[0063] The head portion 35 may be joined to at least one of the outer surface and the inner surface of the coil 10. Furthermore, to prevent the head portion 35 from falling off, a portion of the head portion 35 may be disposed in the lumen 11 at the distal end of the coil 10. The proximal end of the head portion 35 may be located distal to the distal end of the wire 31, or the proximal end of the head portion 35 may be located proximal to the distal end of the wire 31.

[0064] The head portion 35 may be made of a metal material or a resin. Examples of resins that make up the head portion 35 include thermoplastic resins and ultraviolet-curing resins. Examples of resins that can be used to make up the head portion 35 include ester resins such as epoxy acrylate resins, urethane acrylate resins, polyester acrylate resins, and polyethylene terephthalate resins, and olefin resins such as polypropylene. Examples of metals that can be used to make up the head portion 35 include the metals listed in the description of the wire 31. The wire 31 and the head portion 35 may be made of the same material or different materials.

[0065] As shown in Figures 1 to 3, the indwelling device 1 may further have a connecting part 50 disposed in the lumen 11 of the coil 10 and connected to the proximal end of the coil 10, and a pusher 55 connected to the coil 10 via the connecting part 50.

[0066] The indwelling device 1 preferably has a detachment mechanism for detaching the coil 10 from the pusher 55. Examples of detachment mechanisms include hydraulic, electrical, and mechanical mechanisms, and among these, an electrical detachment mechanism is preferably used. In the detachment mechanism, the connection part 50 is preferably heated and cut by electrical or thermal energy supplied via the pusher 55, thereby detaching the coil 10 from the pusher 55. In this case, the connection part 50 is preferably heated by a high-frequency current supplied between the distal end of the pusher 55 and the counter electrode.

[0067] The shape of the connection portion 50 is not particularly limited, and may be a line, a rod, a column, a polygonal column, a cylinder, a polygonal tube, a truncated cone, a truncated polygonal pyramid, or a combination thereof.

[0068] The connecting portion 50 preferably contains a material that melts or dissolves when heated. The connecting portion 50 can be cut by Joule heat. Such a material includes a synthetic resin material, and it is preferable to use a hydrophilic resin of a synthetic polymer substance such as polyvinyl alcohol (PVA), a PVA cross-linked polymer, a PVA water-absorbing gel freeze-thaw elastomer, or a polyvinyl alcohol-based polymer such as an ethylene-vinyl alcohol copolymer.

[0069] The pusher 55 is a rod-shaped or wire-shaped member used to hold the indwelling device 1 and push it distally. The pusher 55 can be composed of one or more members. The pusher 55 can be composed of a wire member, a coil member, or a combination thereof. The pusher 55 can be composed of a conductive material such as stainless steel.

[0070] 1 to 3, a tail portion 36 for closing the proximal end of the coil 10 may be provided at the proximal end of the coil 10. The configuration of the tail portion 36 can be referred to the description of the head portion 35.

[0071] As shown in FIGS. 2 and 3, the drug 60 is preferably disposed distal to the distal end 50 a of the connecting portion 50 in the longitudinal axis direction x of the coil 10 .

[0072] 2 and 3, in the longitudinal axis direction x of the coil 10, the drug 60 is preferably disposed on the inner circumferential surface 13 of the coil 10 and distal to the distal end 50a of the connecting portion 50. In the longitudinal axis direction x of the coil 10, the drug 60 is preferably disposed on the outer circumferential surface 12 of the coil 10 and distal to the distal end 50a of the connecting portion 50.

[0073] As shown in FIGS. 2 and 3, the drug 60 may be disposed proximal to the distal end 50 a of the connecting portion 50 in the longitudinal axis direction x of the coil 10 .

[0074] 2, 3, and 6 to 13, the coil 10 may have a first portion 21 where the coil 10 and the connection portion 50 overlap in the longitudinal axis direction x of the coil 10. The first portion 21 is a portion disposed in the proximal portion of the coil 10, and is preferably disposed at the proximal end portion. Also, as shown in FIG. 2, the coil 10 may have, in the longitudinal axis direction x of the coil 10, the first portion 21 where the coil 10 and the connection portion 50 overlap, and a second portion 25 extending from the distal end 10a of the coil 10 to the distal end 21a of the first portion 21.

[0075] In the longitudinal axis direction x, the second portion 25 is preferably longer than the first portion 21 .

[0076] 2 and 3, the drug 60 may be disposed on the surface of the coil 10 in the first portion 21. The drug 60 may be disposed on the outer peripheral surface 12 of the coil 10 in the first portion 21. The drug 60 may be disposed on the inner peripheral surface 13 of the coil 10 in the first portion 21.

[0077] As shown in Figure 6, it is preferable that no drug 60 is disposed on the surface of coil 10 in first portion 21. It is more preferable that no drug is disposed on outer peripheral surface 12 and inner peripheral surface 13 of first portion 21. In the detachment mechanism, it is preferable that connection portion 50 is heated and cut by electrical or thermal energy, and coil 10 is detached from pusher 55; however, by not disposing drug 60 on first portion 21, the conductivity of coil 10 is ensured, which increases the success rate of detachment and simplifies the operation of placing indwelling device 1.

[0078] In the first portion 21, the drug 60 does not have to be disposed on the entire surface of the coil 10. In the first portion 21, the drug 60 does not have to be disposed on a portion of the surface of the coil 10.

[0079] 3 , a drug is disposed on outer peripheral surface 12 and inner peripheral surface 13 of first portion 21, and the amount of drug per unit coil length on outer peripheral surface 12 of first portion 21 may be less than the amount of drug per unit coil length on inner peripheral surface 13 of first portion 21. The average thickness of the drug layer on outer peripheral surface 12 of first portion 21 may be thinner than the average thickness of the drug layer on inner peripheral surface 13 of first portion 21.

[0080] 2 , a drug is disposed on outer peripheral surface 12 and inner peripheral surface 13 of second portion 25, and the amount of drug per unit coil length on outer peripheral surface 12 of second portion 25 may be less than the amount of drug per unit coil length on inner peripheral surface 13 of second portion 25. The average thickness of the drug layer on outer peripheral surface 12 of second portion 25 may be thinner than the average thickness of the drug layer on inner peripheral surface 13 of second portion 25.

[0081] 2, the amount of drug per unit length of the coil on the surface of the coil 10 in the first portion 21 may be the same as the amount of drug per unit length of the coil on the surface of the coil 10 in the second portion 25. Here, the amount of drug per unit length of the coil on the surface of the coil 10 is the sum of the amount of drug per unit length on the outer peripheral surface 12 of the coil 10 and the amount of drug per unit length on the inner peripheral surface 13.

[0082] Although not shown, the amount of drug per unit length of the coil on the surface of coil 10 of first portion 21 may be greater than the amount of drug per unit length of the coil on the surface of coil 10 of second portion 25. The average thickness of the drug layer on the surface of coil 10 of first portion 21 may be greater than the average thickness of the drug layer on the surface of coil 10 of second portion 25.

[0083] 6 to 12, the amount of drug per unit coil length on the surface of coil 10 in first portion 21 is preferably less than the amount of drug per unit coil length on the surface of coil 10 in second portion 25. In the detachment mechanism, it is preferable that connection portion 50 is heated and cut by electrical or thermal energy, and coil 10 is detached from pusher 55, but since the amount of drug in first portion 21 is less than that in second portion 25, the conductivity of coil 10 is ensured, the rate of successful detachment can be increased, and the operation of placing indwelling device 1 can be performed easily.

[0084] As shown in FIGS. 6 to 12, the average thickness of the drug layer on the surface of coil 10 in first portion 21 is preferably thinner than the average thickness of the drug layer on the surface of coil 10 in second portion 25.

[0085] 6 to 12 , the average thickness of the drug layer on outer peripheral surface 12 of coil 10 in first portion 21 is preferably thinner than the average thickness of the drug layer on outer peripheral surface 12 of coil 10 in second portion 25. The average thickness of the drug layer on inner peripheral surface 13 of coil 10 in first portion 21 is preferably thinner than the average thickness of the drug layer on inner peripheral surface 13 of coil 10 in second portion 25.

[0086] As shown in Figures 3, 6, and 7, when the first portion 21 is divided into two equal parts, a distal first portion 22 and a proximal first portion 23, in the longitudinal axis direction x of the coil 10, the amount of drug per unit length of the coil on the surface of the coil 10 in the proximal first portion 23 may be equal to the amount of drug per unit length of the coil on the surface of the coil 10 in the distal first portion 22.

[0087] 8 to 10 , when the first portion 21 is divided into two equal parts, a distal first portion 22 and a proximal first portion 23, in the longitudinal axis direction x of the coil 10, the amount of drug per unit length of the coil on the surface of the coil 10 in the proximal first portion 23 may be less than the amount of drug per unit length of the coil on the surface of the coil 10 in the distal first portion 22. In FIGS. 8 to 9 , the drug 60 is disposed in both the distal first portion 22 and the proximal first portion 23. In FIG. 10 , the drug 60 is disposed in the distal first portion 22, and the drug 60 is not disposed in the proximal first portion 23.

[0088] 8 , the average thickness of the drug layer on the surface of coil 10 in proximal first portion 23 may be thinner than the average thickness of the drug layer on the surface of coil 10 in distal first portion 22. The average thickness of the drug layer on outer peripheral surface 12 of coil 10 in proximal first portion 23 may be thinner than the average thickness of the drug layer on outer peripheral surface 12 of coil 10 in distal first portion 22. The average thickness of the drug layer on inner peripheral surface 13 of coil 10 in proximal first portion 23 may be thinner than the average thickness of the drug layer on inner peripheral surface 13 of coil 10 in distal first portion 22.

[0089] 8 , the average thickness of the drug layer on inner circumferential surface 13 of coil 10 in proximal first portion 23 may be thinner than the average thickness of the drug layer on outer circumferential surface 12 of coil 10 in distal first portion 22. The average thickness of the drug layer on outer circumferential surface 12 of coil 10 in proximal first portion 23 may be thinner than the average thickness of the drug layer on inner circumferential surface 13 of coil 10 in distal first portion 22.

[0090] As shown in Figure 9, a drug 60 is arranged on the outer surface 12 and inner surface 13 of the distal first portion 22 and the inner surface 13 of the proximal first portion 23, and a drug does not necessarily have to be arranged on the outer surface 12 of the proximal first portion 23.

[0091] As shown in Figure 10, a drug 60 is arranged on the outer surface 12 and inner surface 13 of the distal first portion 22, and a drug does not necessarily have to be arranged on the outer surface 12 and inner surface 13 of the proximal first portion 23.

[0092] Although not shown in the figure, a drug 60 is arranged on the outer surface 12 and inner surface 13 of the distal first portion 22 and the outer surface 12 of the proximal first portion 23, and a drug does not necessarily have to be arranged on the inner surface 13 of the proximal first portion 23.

[0093] 11 and 12 , when the first portion 21 is divided into two equal parts, a distal first portion 22 and a proximal first portion 23, in the longitudinal axis direction x of the coil 10, the amount of drug per unit area of ​​the coil on the surface of the coil 10 in the proximal first portion 23 may be greater than the amount of drug per unit area of ​​the coil on the surface of the coil 10 in the distal first portion 22. In Fig. 11 , the drug 60 is disposed on both the distal first portion 22 and the proximal first portion 23. In Fig. 12 , the drug 60 is disposed on the proximal first portion 23, and no drug 60 is disposed on the distal first portion 22.

[0094] As shown in FIG. 11 , the average thickness of the drug layer on the surface of the coil 10 in the proximal first portion 23 may be thicker than the average thickness of the drug layer on the surface of the coil 10 in the distal first portion 22.

[0095] 11 , the average thickness of the drug layer on outer peripheral surface 12 of coil 10 in proximal first portion 23 may be greater than the average thickness of the drug layer on outer peripheral surface 12 of coil 10 in distal first portion 22. The average thickness of the drug layer on inner peripheral surface 13 of coil 10 in proximal first portion 23 may be greater than the average thickness of the drug layer on inner peripheral surface 13 of coil 10 in distal first portion 22. The average thickness of the drug layer on outer peripheral surface 12 of coil 10 in distal first portion 22 may be less than the average thickness of the drug layer on inner peripheral surface 13 of coil 10 in proximal first portion 23.

[0096] As shown in Figure 12, a drug 60 is arranged on the outer surface 12 and inner surface 13 of the proximal first portion 23, and a drug does not have to be arranged on the outer surface 12 and inner surface 13 of the distal first portion 22.

[0097] Although not shown in the figure, a drug 60 is arranged on the outer surface 12 and inner surface 13 of the proximal first portion 23 and the inner surface 13 of the distal first portion 22, and the drug 60 does not have to be arranged on the outer surface 12 of the distal first portion 22.

[0098] Although not shown in the figure, a drug 60 is arranged on the outer surface 12 and inner surface 13 of the proximal first portion 23 and the outer surface 12 of the distal first portion 22, and the drug 60 does not have to be arranged on the inner surface 13 of the distal first portion 22.

[0099] 13 , when the coil 10 has a distal first portion 22 and a proximal first portion 23, the average outer diameter of the proximal first portion 23 may be smaller than the average outer diameter of the distal first portion 22. In this case, it is preferable that the amount of drug per unit area of ​​the coil on the surface of the coil 10 in the proximal first portion 23 is greater than the amount of drug per unit area of ​​the coil on the surface of the coil 10 in the distal first portion 22.

[0100] The average inner diameter of the distal first portion 22 refers to the arithmetic mean of the inner diameters of the coil 10 measured at each position in the longitudinal axis direction x throughout the entire distal first portion 22. The same applies to the average inner diameters of other portions. The inner and outer diameters of the coil 10 can be measured using a known size measuring device.

[0101] As shown in Figure 13, the coil 10 may have a first transitional section 14 in which the outer diameter decreases toward the proximal side. This makes it easier to secure the coil 10 to the connection section 50. The first transitional section 14 may be located in the first section 21 or the second section 25, but is preferably located from the first section 21 to the second section 25. The first transitional section 14 may be located in the proximal first section 23, but is preferably located in the distal first section 22. The first transitional section 14 is preferably not located in the proximal first section 23.

[0102] When the coil 10 is divided into two equal parts, a distal part and a proximal part, in the longitudinal axis direction x, the average outer diameter of the coil 10 at the proximal part may be smaller than the average outer diameter at the distal part.

[0103] 13 , the average outer diameter of the first portion 21 is preferably smaller than the average outer diameter of the second portion 25. The average outer diameter of the distal first portion 22 is preferably smaller than the average outer diameter of the second portion 25. The average outer diameter of the proximal first portion 23 is preferably smaller than the average outer diameter of the second portion 25.

[0104] As shown in FIG. 13 , the average outer diameter of the proximal first portion 23 is preferably smaller than the average outer diameter of the distal first portion 22 .

[0105] The first portion 23 may be in contact with the connecting portion 50. The proximal first portion 23 may be in contact with the connecting portion 50. Furthermore, the distal first portion 22 may be in contact with the connecting portion 50. It is preferable that the inner circumferential surface 13 side of the first portion 23 be in contact with the outer surface of the connecting portion 50.

[0106] Although not shown, the coil 10 may have a second transition section in which the outer diameter decreases distally, thereby allowing the flexibility of the coil 10 to gradually increase from the distal to the proximal side.

[0107] In the first transition section 14 and / or the second transition section, the outer diameter of the coil 10 may taper toward the proximal or distal side. Here, "tapered" includes a configuration in which the outer diameter of the wire 31 constituting the coil 10 decreases with each turn, resulting in a tapered envelope of the outer diameter of the coil 10.

[0108] In the first transition section 14 and / or the second transition section, the outer diameter of the coil 10 may decrease in a stepwise manner toward the proximal or distal side. Here, "stepwise" includes a form in which the outer diameter of the wire 31 constituting the coil 10 decreases at least every two or more turns.

[0109] As shown in Figure 2, it is preferable that the drug 60 is disposed only on the surface of the coil 10, and that the lumen 11 of the coil 10 is not filled with the drug 60. Here, "filled" means that the drug 60 is present so as to block the cross section of the lumen 11.

[0110] The type of drug 60 is not particularly limited as long as it is necessary for the prevention and treatment of the affected area. The drug 60 may have at least one of an anti-inflammatory effect, an antioxidant effect, a hypotensive effect, and a shear stress sensing inhibitory effect. Examples of the drug 60 include selective serotonin reuptake inhibitors (SSRIs), DPP-4 inhibitors, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs, angiotensin II receptor antagonists, tocopherol acetate, ascorbic acid, edaravone, N-acetyl-L-cysteine, calcium channel blockers, diuretics, angiotensin II receptor antagonists (ARBs), angiotensin-converting enzyme inhibitors (ACEs), β-blockers, α-blockers, αβ-blockers, etc.

[0111] The drug 60 may be directly attached to the surface of the coil 10, or may be indirectly attached to the surface of the coil 10 via a bioadhesive. There are no particular limitations on the type of material for the bioadhesive, but examples that can be used include polysaccharide adhesives such as collagen, chitosan, and gelatin, polyethylene glycol-based hydrogel adhesives, and protein adhesives such as fibrin and collagen.

[0112] The drug 60 may be held on the surface of the coil 10 as a drug layer. The drug 60 may be held on the surface of the coil 10 in the form of a capsule such as a microcapsule. The drug 60 encapsulated in the capsule may be held on the surface of the coil 10 in the form of a layer.

[0113] The drug 60 is preferably encapsulated in a capsule, so that the drug 60 can be released effectively when the coil 10 is delivered to an affected area in a living body. The drug 60 encapsulated in the capsule may be directly attached to the surface of the coil 10, or may be indirectly attached to the surface of the coil 10 via a bioadhesive.

[0114] The capsule size is preferably 10 nm or more, more preferably 50 nm or more, even more preferably 100 nm or more, and is preferably 500 nm or less, more preferably 400 nm or less, even more preferably 200 nm or less.

[0115] The drug 60 is preferably encapsulated in a capsule containing a biodegradable material. Examples of biodegradable materials include bioabsorbable polymers, natural polymers, decellularized biological tissues and cells, and combinations thereof. Examples of bioabsorbable polymers include at least one of polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), lactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), and polydioxanone (PDS). Examples of natural polymers include at least one of collagen, laminin, fibroin, gelatin, glycosaminoglycans, chitin, chitosan, hyaluronic acid, and polypeptides. Among these, PLGA is preferred as a biodegradable material.

[0116] The capsule preferably has a structure in which a plurality of filamentous bioabsorbable polymers are condensed into a spherical shape. The number of filamentous bioabsorbable polymers is preferably 10,000 or more, more preferably 20,000 or more, and even more preferably 30,000 or more. The number of filamentous bioabsorbable polymers may be 100,000 or less, 90,000 or less, or 80,000 or less. In particular, the capsule preferably has a structure in which 10,000 to 100,000 PLGA filaments are condensed into a spherical shape.

[0117] The glass transition temperature of the material constituting the capsule is not particularly limited, but may be, for example, 40°C or higher, 41°C or higher, or 42°C or higher, and is also acceptable to be 50°C or lower, 49°C or lower, or 48°C or lower.

[0118] The surface of the capsule is preferably covered with a coating material. The coating material can prevent the drug 60 from eluting into the blood or falling off during delivery of the indwelling device 1 into the body. The material constituting the coating material is preferably a water-soluble polymer from the viewpoint of preventing an initial burst of the drug 60. Examples of materials for the coating material include carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol, alginic acid, pectin, gum arabic, gellan gum, guar gum, xanthan gum, carrageenan, and gelatin.

[0119] A surfactant may be applied to the surface of the capsule. The application of a surfactant increases the fluidity of the capsule's cell membrane, thereby improving the permeability of the drug through the cell membrane. The type of surfactant is not particularly limited, but a nonionic surfactant is preferred, such as polyoxyethylene sorbitan monolaurate, preferably Tween (registered trademark) 20 or Tween (registered trademark) 80.

[0120] The coil hardness of coil 10 is 5.0 x 10 －９ The hardness of the coil 10 refers to the hardness of the coil in the state of a primary coil. The hardness S (unit: N / mm) of the coil 10 can be calculated by the following formula: S=D １ ４ ×G / (8D ２ ３ ×n) As shown in Figure 2, １ is the outer diameter of the wire 31 (unit: mm), D ２ is the outer diameter of the coil 10 (unit: mm). The number of turns n (unitless) of the coil 10 refers to the number of turns that can be counted when the coil 10 is viewed from the side at an angle that results in the largest number of turns. The shear modulus G (unit: Pa (N / mm ２ )) is a value that differs depending on the material that constitutes the wire 31, and if the chemical components of the material that constitutes the wire 31 are the same, the value of the shear modulus G will be the same. Note that the hardness of the coil 10 is preferably calculated in a state before the drug 60 is applied.

[0121] When calculating the coil hardness, the outer diameter D of the wire 31 １ , outer diameter D of the coil 10 ２ A value measured by a measuring means such as a vernier caliper, a micrometer, or an image dimension measuring instrument may be used as the distance.

[0122] When calculating the coil hardness, the outer diameter D of the wire 31 １ , outer diameter D of the coil 10 ２ At least one of the number of turns n of the coil 10 may be a value listed in the coil product catalog.

[0123] The coil hardness of the coil 10 is 8.0 x 10 －９ N / mm or more, 1.0×10 －８ The coil hardness of the coil 10 may be 3.5×10 －８ N / mm or less, 3.0 x 10 －８ N / mm or less, 2.0×10 －８ By disposing the drug in a coil with such hardness, it is possible to apply the amount of drug required for treatment to the affected area while minimizing the impact of reduced operability.

[0124] When the length of the coil 10 is divided into two equal halves along the longitudinal axis x into a distal portion and a proximal portion, it is preferable that the coil stiffness in the proximal portion be smaller than that in the distal portion. This allows the proximal portion to be formed to be more flexible than the distal portion. The coil stiffness in the proximal portion is preferably 0.9 times or less, more preferably 0.8 times or less, and even more preferably 0.7 times or less, of the coil stiffness in the distal portion, and is also acceptable to be 0.3 times or more, 0.4 times or more, or 0.5 times or more.

[0125] 2. Manufacturing Method of In-Vivo Indwelling Device The manufacturing method of an in-vivo indwelling device according to the first embodiment is characterized in that it includes the steps of preparing a wire and a drug (step S1), applying the drug to only a partial circumferential section of the wire (step S2), and winding the drug-applied wire to form a first coil (step S3). The manufacturing method of an in-vivo indwelling device according to the second embodiment is characterized in that it includes the steps of preparing a wire and a drug (step S11), applying a first predetermined amount of drug to a first circumferential section of the wire and applying a second predetermined amount of drug, which is smaller than the first predetermined amount, to a second circumferential section of the wire that is located at a different position from the first section (step S12), and winding the drug-applied wire to form a first coil (step S13). The manufacturing method of the in-vivo indwelling device according to the third embodiment includes the steps of preparing a second coil to which no drug has been applied and a storage section containing the drug (step S21), immersing the second coil in the storage section to apply the drug to the surface of the second coil (step S22), and removing only a portion of the drug applied to the outer surface of the second coil (step S23). According to the manufacturing method of the in-vivo indwelling device according to the first to third embodiments, an in-vivo indwelling device that is likely to enhance sustained drug release by disposing a drug on the inner surface of the first or second coil can be obtained. Furthermore, by disposing a larger amount of drug on the inner surface than on the outer surface, or by disposing no drug on the outer surface, frictional resistance during delivery to the treatment site can be reduced, and the amount of drug that may fall off during delivery can be reduced, resulting in an in-vivo indwelling device that is likely to efficiently deliver the drug required for treatment to the treatment site.

[0126] (First embodiment) A method for manufacturing an in-vivo indwelling device according to a first embodiment of the present invention will be described with reference to Figs. 14 to 18. Fig. 14 is a flowchart showing a method for manufacturing an in-vivo indwelling device according to a first embodiment of the present invention. Fig. 15 is a cross-sectional view showing an example of applying a drug to a wire in step S2 of the manufacturing method shown in Fig. 14. Fig. 16 is a perspective view showing an example of applying a drug to a wire in step S2 of the manufacturing method shown in Fig. 14. Fig. 17 is a cross-sectional view showing an example of forming a first coil in step S3 of the manufacturing method shown in Fig. 14. Fig. 18 is a flowchart showing a modification of the manufacturing method shown in Fig. 14.

[0127] As shown in FIG. 14, a wire 101 and a chemical agent 130 are prepared (step S1).

[0128] In step S1, it is preferable to prepare wire 101 having no drug 130 applied to its surface. For the configuration of wire 101, please refer to the explanation of wire 31 in "1. In-vivo indwelling device."

[0129] 14 to 16, the drug 130 is applied to only a partial section in the circumferential direction n of the wire 101 (step S2). For the configuration of the drug 130, please refer to the explanation of the drug 60 in "1. In-vivo indwelling device."

[0130] In step S2, it is preferable to apply a chemical agent 130 to the outer surface of the wire 101.

[0131] In step S2, the chemical agent 130 may be applied only to a part of the section in the circumferential direction n of the wire 101 in at least a part of the section in the longitudinal axis direction m of the wire 101. For this reason, the chemical agent 130 may be applied only to a part of the section in the circumferential direction n of the wire 101 in a part of the section in the longitudinal axis direction m of the wire 101, and the chemical agent 130 may be applied to the entire section in the circumferential direction n of the wire 101 in the remaining part of the section in the longitudinal axis direction m of the wire 101.

[0132] In step S2, it is preferable to apply the chemical agent 130 to only a partial section of the wire 101 in the circumferential direction n, over the entire length of the wire 101 in the longitudinal axis direction m.

[0133] In step S2, for example, the chemical agent 130 may be applied only to a range of 10% or more, 20% or more, or 30% or more of the circumferential length of the wire 101, or may be applied only to a range of 70% or less, 60% or less, or 50% or less of the circumferential length of the wire 101. The circumferential length of the wire 101 refers to the circumferential length of the outer periphery of the wire 101 in a cross section perpendicular to the longitudinal axis direction m of the wire 101.

[0134] In step S2, the method for applying the chemical 130 to the surface of the wire 101 is not particularly limited. Examples of methods for applying the chemical 130 include brush coating, roll coating, dip coating, and spray coating. In any of these methods, the chemical 130 applied to the surface of the wire 101 may be a liquid chemical, or a solution in which capsules containing a chemical are present in a solvent. The chemical 130 may be applied once or twice or more times.

[0135] The type of solvent that can be used to apply drug 130 is not particularly limited as long as it is a solvent in which drug 130 can be dissolved or dispersed, but from the standpoints of availability and bioavailability (safety), ethanol, methanol, acetone, ethyl acetate, acetonitrile, N,N-dimethylacetamide, propanol, chloroform, benzyl alcohol, ethanol, and acetone are preferred, and tetrahydrofuran and dimethyl sulfoxide are particularly preferred.

[0136] After completion of step S2, the drug 130 may be held on the surface of the wire 101 as a drug layer, or may be held on the surface of the wire 101 in the form of microcapsules or the like.

[0137] In step S2, the drug 130 may be applied to the coil via a bioadhesive. For the bioadhesive, the explanation given in "1. Intra-vivo indwelling device" can be referred to.

[0138] 14 and 17, the wire 101 to which the chemical agent 130 has been applied is wound to form the first coil 110 (step S3). In step S3, the wire 101 to which the chemical agent 130 has been applied may be wound around a mandrel having an outer diameter corresponding to the desired inner diameter of the coil, or a known winding machine may be used.

[0139] In step S3 of winding the wire 101 to which the drug 130 has been applied to form the first coil 110, it is preferable to wind the wire 101 to which the drug 130 has been applied so that the section of the wire 101 to which the drug 130 has been applied is located on the inner circumferential side of the first coil 110, as shown in FIG. 17 . This makes it possible to obtain a first coil 110 in which the drug 130 is applied on the inner circumferential surface and the drug 130 is not applied on the outer circumferential surface. Disposing the drug 130 on the inner circumferential surface 113 of the first coil 110 facilitates enhanced sustained drug release. Furthermore, disposing more drug 130 on the inner circumferential surface than on the outer circumferential surface facilitates reduced frictional resistance during delivery to the treatment site and reduces the amount of drug that may fall off during delivery, thereby facilitating efficient delivery of the drug 130 required for treatment to the treatment site.

[0140] In step S3, the wire 101 to which the drug 130 has been applied may be wound so that at least a portion of the section of the wire 101 to which the drug 130 has been applied is located on the inner side of the first coil 110, and the remaining portion is located on the outer side of the first coil 110.

[0141] In step S3, it is preferable to wind the wire 101 to which the drug 130 has been applied so that the entire section of the wire 101 to which the drug 130 has been applied is located on the inner periphery side of the first coil 110.

[0142] As shown in Figure 18, the manufacturing method of the in-vivo indwelling device according to the first embodiment preferably includes a step (step S4) of reducing the outer diameter of the first coil 110. Reducing the outer diameter of the first coil 110 facilitates fixing the first coil 110 to the connection portion (e.g., the connection portion 50 in Figures 1 to 3). For example, the outer diameter of the first coil 110 may be reduced in the longitudinal direction of the first coil 110 after a portion of the connection portion is disposed in the lumen of the first coil 110. Reducing the outer diameter of the first coil 110 may also bring the first coil 110 into close contact with the surface of the connection portion 50. In other words, the first coil 110 may be crimped to the connection portion 50. This facilitates fixing the first coil 110 to the connection portion 50.

[0143] In step S4, the outer diameter of the first coil 110 may be reduced by pinching the outer surface of one end of the first coil 110 in the longitudinal axis direction with a clamping member and crimping the grasped first coil 110 onto the outer periphery of the connection portion.

[0144] In step S4, the coil wall at one end of the first coil 110 in the longitudinal direction may be pinched with a clamping member, and the grasped first coil 110 may be pulled, thereby reducing the outer diameter of the first coil 110.

[0145] The clamping member used in step S4 may be, for example, tweezers.

[0146] In step S4, it is preferable to reduce the outer diameter of only a portion of the first coil 110 in the longitudinal axis direction. In step S4, the total length of the first coil 110 in the longitudinal axis direction of the first coil 110 may be 50 times or more, 80 times or more, 100 times or more, or 5000 times or less, 4000 times or less, or 3000 times or less, the length of the portion whose outer diameter is reduced.

[0147] In step S4, the length of the portion of the first coil 110 where the outer diameter is reduced in the longitudinal axis direction is preferably 2 or more, 3 or more, 4 or more, and 10 or less, 8 or less, or 6 or less pitches of the first coil 110. In this specification, the term "pitch" refers to the distance from the central axis to the central axis of adjacent wire rods 101 when the first coil 110 is viewed in the radial direction, and refers to the portion having the longest length.

[0148] Second Embodiment A method for manufacturing an in-vivo indwelling device according to a second embodiment of the present invention will be described with reference to Figs. 19 to 23. Fig. 19 is a flowchart showing a method for manufacturing an in-vivo indwelling device according to the second embodiment of the present invention. Fig. 20 is a cross-sectional view showing an example of applying a drug to a wire in step S12 of the manufacturing method shown in Fig. 19. Fig. 21 is a perspective view showing an example of applying a drug to a wire in step S12 of the manufacturing method shown in Fig. 19. Fig. 22 is a cross-sectional view showing an example of forming a first coil in step S13 of the manufacturing method shown in Fig. 19. Fig. 23 is a flowchart showing a modification of the manufacturing method shown in Fig. 19.

[0149] 19, a wire 101 and a drug 130 are prepared (step S11). The configuration of step S11 can be referred to the description of step S1.

[0150] As shown in Figures 19 to 21, a first predetermined amount of drug 130 is applied to a first section 105 in the circumferential direction n of the wire 101, and a second predetermined amount of drug 130 smaller than the first predetermined amount is applied to a second section 106 located at a different position from the first section 105 in the circumferential direction n of the wire 101 (step S12).

[0151] In step S12, it is preferable to apply a chemical agent 130 to the outer surface of the wire 101.

[0152] As shown in FIG. 21, in step S12, it is preferable that the first section 105 and the second section 106 of the wire 101 each extend from one end to the other end of the wire 101 in the longitudinal axis direction m.

[0153] Hereinafter, the amount of drug (mg / mm) per unit length of wire 101 in the longitudinal axis direction m of wire 101 may be simply referred to as the amount of drug per unit length of wire 101. In step S12, it is preferable that the amount of drug per unit length of wire 101 in second section 106 is smaller than the amount of drug per unit length of wire 101 in first section 105.

[0154] In the circumferential direction n of the wire rod 101, the length of the first section 105 may be shorter than the length of the second section 106. In the circumferential direction n of the wire rod 101, the length of the first section 105 may be longer than the length of the second section 106. As shown in Fig. 20 , in the circumferential direction n of the wire rod 101, the length of the first section 105 may be the same as the length of the second section 106.

[0155] Although not shown, the lengths of the first section 105 and the second section 106 may differ depending on the position in the longitudinal axis direction m of the wire rod 101. For example, the length of the first section 105 may be longer than the length of the second section 106 at a first position in the longitudinal axis direction m of the wire rod 101, and the length of the first section 105 may be shorter than the length of the second section 106 at a second position in the longitudinal axis direction m of the wire rod 101 that is different from the first position.

[0156] In step S12, it is preferable that no sections other than the first section 105 and the second section 106 exist in the circumferential direction n of the wire 101. In other words, it is preferable that the chemical agent 130 is applied to the entire circumferential direction n of the wire 101 at least in a cross section perpendicular to the longitudinal axis direction m at an arbitrary position in the longitudinal axis direction m of the wire 101.

[0157] In step S12, a third predetermined amount of the chemical substance 130, which is smaller than the second predetermined amount, may be applied to a third section that is located at a position different from the first section 105 and the second section 106 in the circumferential direction n of the wire 101. In addition, in step S2, the chemical substance 130 may not be applied to the third section that is located at a position different from the first section 105 and the second section 106 in the circumferential direction n of the wire 101.

[0158] In step S12, it is preferable that the first section 105 and the second section 106 are adjacent to each other in the circumferential direction n of the wire 101.

[0159] For the configuration of the drug 130, please refer to the explanation of the drug 60 in "1. In-vivo indwelling device." For the method of applying the drug 130 to the wire 101, please refer to the explanation of step S2.

[0160] 19, the wire 101 to which the chemical agent 130 has been applied is wound to form the first coil 110 (step S13). For step S13, the description of step S3 can be referred to.

[0161] 22 , in step S13, it is preferable to wind wire 101 to which drug 130 has been applied so that first section 105 is located on the inner circumferential side of first coil 110 and second section 106 is located on the outer circumferential side of first coil 110. This makes it possible to make the amount of drug per unit length of the coil on the outer circumferential surface of first coil 110 smaller than the amount of drug per unit length of the coil on the inner circumferential surface of first coil 110.

[0162] 23, the method for manufacturing the in-vivo indwelling device according to the second embodiment preferably includes a step (step S14) of reducing the outer diameter of first coil 110. For step S14, the description of step S4 can be referred to.

[0163] (Third embodiment) A method for manufacturing an in-vivo indwelling device according to a third embodiment of the present invention will be described with reference to Figures 24 and 25. Figure 24 is a flowchart showing a method for manufacturing an in-vivo indwelling device according to the third embodiment of the present invention. Figure 25 is a flowchart showing a modification of the manufacturing method shown in Figure 24.

[0164] 24, a second coil to which no drug is applied and a reservoir portion in which a drug is stored are prepared (step S21). For the configuration of the second coil, the description of coil 10 in "1. In-vivo indwelling device", particularly the configuration regardless of whether or not a drug 60 is present, can be referred to.

[0165] In step S21, it is preferable that a liquid containing a drug (active ingredient) is stored in the storage section.

[0166] The storage unit may be connected to a supply means for supplying the drug into the storage unit. Examples of the supply means include a hopper, a supply pipe, and a supply pump. The storage unit may be a storage tank. The shape of the storage tank is not particularly limited, but examples include a roughly cylindrical body or a roughly rectangular parallelepiped body. The vertical length of the storage tank may be longer or shorter than its horizontal length. The storage unit may be provided with a mechanism for homogenizing the drug in the storage tank, such as a stirring means.

[0167] In step S21, multiple storage units may be prepared. The multiple storage units may include, for example, a first storage unit and a second storage unit. This allows, for example, in step S21, the drug stored in the first storage unit to be applied to a portion of the second coil, and the drug stored in the second storage unit to be applied to another portion of the coil. As a result, different types of drug can be applied to one portion and another portion of the second coil, or the amount of drug per unit length of the second coil can be made different. The first storage unit and the second storage unit may be disposed within a single storage tank, or the first storage unit may be disposed in the first storage tank, and the second storage unit may be disposed in the second storage tank.

[0168] In step S21, the first and second reservoirs may store liquids containing the same type of drug (active ingredient). Alternatively, in step S21, the first and second reservoirs may store liquids containing different types of drug (active ingredient).

[0169] As shown in FIG. 24, the second coil is immersed in the reservoir and the drug is applied to the surface of the second coil (step S22).

[0170] In step S22, the second coil may be entirely immersed in the reservoir, thereby applying the drug to both the outer and inner surfaces of the second coil.

[0171] In step S22, only a portion of the second coil may be immersed in the reservoir. For example, it is preferable that a portion of the second coil in the longitudinal direction is immersed in the reservoir, and the other portion of the second coil in the longitudinal direction is not provided with the drug.

[0172] As shown in Figure 24, only a portion of the drug applied to the outer peripheral surface of the second coil is removed (step S23), thereby making it possible to reduce the amount of drug per unit length on the outer peripheral surface of the coil compared to the amount of drug per unit length on the inner peripheral surface of the coil.

[0173] In step S23, examples of methods for removing the chemicals include grinding with a file or squeegee, and using a remover.

[0174] In step S23, it is preferable that the drug applied to the inner circumferential surface of the second coil is not removed.

[0175] 25, the manufacturing method according to the third embodiment preferably includes a step of reducing the outer diameter of the second coil (step S24). Step S24 is preferably performed after step S23. For step S24, the description of step S4 can be referred to.

[0176] (Steps common to the first to third embodiments) The manufacturing methods according to the first to third embodiments may further include at least one of the following steps S30 to S32: a step of preparing a pusher for pushing the first or second coil distally (step S30); a step of preparing a connection part for connecting the first or second coil and the pusher (step S31); and a step of connecting the first or second coil and the pusher via the connection part (step S32).

[0177] For the configuration of the pusher and the connecting part, reference can be made to the explanation of the pusher 55 and the connecting part 50 in "1. In-vivo indwelling device."

[0178] In step S32, the proximal end of the first coil or the second coil is preferably connected to the distal end of the connection part, and the proximal end of the connection part is preferably connected to the distal end of the pusher.

[0179] In step S32, the method of connecting the first coil or the second coil to the connection part, or the connection part to the pusher, can be exemplified by methods such as welding, crimping, adhesive bonding, physical fastening such as engagement, coupling, binding, ligation, or a combination thereof. Here, "connection" includes 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.

[0180] When carrying out the manufacturing methods according to the first to third embodiments, the configurations and methods described in "1. In-vivo indwelling device" can be referred to as appropriate.

[0181] This application claims the benefit of priority based on Japanese Patent Application No. 2024-104814, filed on June 28, 2024. The entire contents of the specification of Japanese Patent Application No. 2024-104814, filed on June 28, 2024, are incorporated herein by reference.

[0182] 1: In-vivo indwelling device 10: Coil 11: Lumen 12: Outer circumferential surface 13: Inner circumferential surface 21: First portion 22: Distal side first portion 23: Proximal side first portion 25: Second portion 31: Wire 35: Head portion 40: Stretch resistance member 41: Folded portion 50: Connection portion 55: Pusher 60: Drug 101: Wire 105: First section 106: Second section 110: First coil 130: Drug x: Longitudinal axis direction of coil y: Radial direction of coil z: Circumferential direction of coil m: Longitudinal axis direction of wire n: Circumferential direction of wire

Claims

1. An in-vivo indwelling device having a coil with a drug disposed on its surface, wherein the amount of drug per unit length on the outer circumferential surface of the coil is less than the amount of drug per unit length on the inner circumferential surface of the coil.

2. The in-vivo indwelling device according to claim 1, further comprising a stretch resistance member disposed within the lumen of the coil, the stretch resistance member having a drug disposed on its surface.

3. The in-vivo indwelling device according to claim 1 or 2, further comprising a connecting part disposed in the lumen of the coil and connected to the proximal end of the coil, and a pusher connected to the coil via the connecting part, and the drug is disposed distal to the distal end of the connecting part in the longitudinal axis direction of the coil.

4. The in-vivo indwelling device according to claim 3, wherein the coil has a first portion where the coil and the connecting portion overlap in the longitudinal axis direction of the coil, and no drug is disposed on the surface of the coil in the first portion.

5. An in-vivo indwelling device as described in claim 3, wherein the coil has a first portion where the coil and the connecting portion overlap in the longitudinal axis direction of the coil, and a second portion from the distal end of the coil to the distal end of the first portion, and the amount of drug per unit length of the coil on the surface of the coil in the first portion is less than the amount of drug per unit length of the coil on the surface of the coil in the second portion.

6. An in-vivo indwelling device as described in claim 5, wherein when the first portion is divided into two equal parts, a distal first portion and a proximal first portion, in the longitudinal direction of the coil, the amount of drug per unit length of the coil on the surface of the coil in the proximal first portion is less than the amount of drug per unit length of the coil on the surface of the coil in the distal first portion.

7. An in-vivo indwelling device as described in claim 5, wherein when the first portion is divided into two equal parts, a distal first portion and a proximal first portion, in the longitudinal direction of the coil, the amount of drug per unit area length of the coil on the surface of the coil in the proximal first portion is greater than the amount of drug per unit area length of the coil on the surface of the coil in the distal first portion.

8. The coil hardness of the coil is 5.0 x 10 －９ 3. The in-vivo indwelling device according to claim 1, wherein the strength is at least N / mm.

9. The in-vivo indwelling device according to claim 1 or 2, wherein the drug is encapsulated in a capsule containing a biodegradable material.

10. The in-vivo indwelling device according to claim 1 or 2, wherein the drug has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, and shear stress sensing inhibitory effect.

11. A method for manufacturing an in-vivo indwelling device, comprising the steps of: preparing a wire and a drug; applying the drug to only a partial circumferential section of the wire; and winding the drug-applied wire to form a first coil.

12. A method for manufacturing an in-vivo indwelling device as set forth in claim 11, wherein in the step of winding the drug-impregnated wire to form a first coil, the drug-impregnated wire is wound so that the section of the drug-impregnated wire to which the drug is imparted is located on the inner periphery of the first coil.

13. A method for manufacturing an in-vivo indwelling device, comprising the steps of: preparing a wire and a drug; applying a first predetermined amount of drug to a first circumferential section of the wire, and applying a second predetermined amount of drug, which is less than the first predetermined amount, to a second circumferential section of the wire that is located at a different position from the first section; and winding the drug-applied wire to form a first coil.

14. A method for manufacturing an in-vivo indwelling device as described in claim 13, wherein in the step of winding the drug-loaded wire to form a first coil, the drug-loaded wire is wound so that the first section is located on the inner side of the first coil and the second section is located on the outer side of the first coil.

15. The method of manufacturing an in-vivo indwelling device according to claim 11 or 13, further comprising the step of reducing the outer diameter of the first coil.

16. A method for manufacturing an in-vivo indwelling device, comprising the steps of: preparing a second coil to which no drug has been applied and a storage section in which a drug has been stored; immersing the second coil in the storage section to apply a drug to the surface of the second coil; and removing only a portion of the drug applied to the outer surface of the second coil.

17. The method of manufacturing an in-vivo indwelling device according to claim 16, further comprising the step of reducing the outer diameter of the second coil.

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