In-vivo implantation system

Abstract

The present invention provides an in-vivo implantation system that enhances drug sustained release and facilitates the placement of coils within aneurysms. [Solution] An in-vivo implantation system 100 comprising: a first implantation device 1 having a first coil 101 and a first fiber layer disposed on the outer surface of the first coil 101; and a second implantation device 2 having a second coil 102 and a second fiber layer disposed on the outer surface of the second coil 102, wherein the first fiber layer and the second fiber layer each contain fibers containing a polymer material and a drug, and the mass per unit length of coil of the second fiber layer is less than the mass per unit length of coil of the first fiber layer.

Description

[Technical Field]

[0001] The present invention relates to an implantation system equipped with an in vivo implantable device for forming an embolism in a blood vessel in a diseased area of ​​the body. [Background technology]

[0002] Endovascular treatment is one of the treatment methods for vascular lesions such as aneurysms of the head and neck, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, and aneurysms of the renal arteries and abdominal arteries. In endovascular treatment, embolization is used, which involves implanting an in vivo device containing coils for embolization at the target site to promote thrombosis and prevent, for example, the rupture of an aneurysm. Several to tens of coils are used in a single embolization procedure. Patent documents 1 to 3 disclose in vivo devices in which coils hold medication. [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] U.S. Patent Application Publication No. 2007 / 299461 [Patent Document 2] Special Publication No. 2013-537046 [Patent Document 3] Japanese Patent Publication No. 2015-195978 [Overview of the project] [Problems that the invention aims to solve]

[0004] As described in Patent Documents 1 to 3, applying a drug to a coil can cause the coil to harden, making it difficult to place the coil inside the aneurysm. Therefore, the present invention aims to provide an in-vivo implantation system that can improve drug sustained release and facilitate the placement of the coil inside the aneurysm. [Means for solving the problem]

[0005] The implantation system for an in-vivo device according to an embodiment that has been able to solve the above problems is as follows. [1] A first retaining device having a first coil and a first fiber layer disposed on the outer surface of the first coil, The device comprises a second retaining device having a second coil and a second fiber layer disposed on the outer surface of the second coil, The first fiber layer and the second fiber layer each contain fibers containing a polymer material and a drug, An implantation system for an in-vivo device in which the mass per unit length of the second fiber layer is less than the mass per unit length of the first fiber layer.

[0006] Furthermore, the implantation system for the in-vivo implantation device according to the embodiment is preferably one of the following [2] to [7]. [2] The implantation system for an in vivo implantation device according to [1], wherein the fiber includes a core-sheath type fiber having a core and a sheath, the core containing the drug and the sheath containing the polymer material. [3] The implantation system for an in-vivo implantation device according to [1] or [2], wherein the mass per unit length of the first fiber layer located in the proximal part of the first coil is less than the mass per unit length of the first fiber layer located in the distal part of the first coil. [4] The implantation system for an in-vivo implantation device according to any one of the following items: [1] to [3], wherein the mass per unit length of the second fiber layer located in the proximal part of the second coil is less than the mass per unit length of the second fiber layer located in the distal part of the second coil. [5] The implantation system for an in-vivo implantation device according to any one of the following: [1] to [4], wherein the mass per unit length of the second fiber layer located distal to the second coil is less than the mass per unit length of the first fiber layer located proximal to the first coil. [6] An in-vivo implantation system according to any one of the claims [1] to [3], wherein the second fiber layer is provided only in the distal portion of the second coil, and the second fiber layer is not provided in the proximal portion of the second coil. [7] The polymer material is a biodegradable polymer material. [1] to [6] The implantation system for an in-vivo device according to any one of these items. [Effects of the Invention]

[0007] In the above-described in-vivo implantation system, the first and second fiber layers each contain polymer materials and drug-containing fibers, respectively. This prevents the drug from detaching from the coil early in the procedure and enhances drug release, compared to cases where the drug is coated on the coil surface. While adding a fiber layer to the coil surface tends to make the coil stiffer, the mass of the fiber layer per unit length of the coil is less in the second coil than in the first coil, allowing the second coil to be more flexible than the first coil. Therefore, by introducing the second coil into the body after the first coil, it becomes easier to locate empty spaces within the aneurysm using the first coil and place the first coil deep within the aneurysm, preventing the first coil from detaching outside the aneurysm. Furthermore, it facilitates the subsequent operation of folding and packing the second coil into the aneurysm. [Brief explanation of the drawing]

[0008] [Figure 1] This is a schematic diagram of the implantation system for an in-vivo device according to an embodiment. [Figure 2] Figure 1 shows a cross-sectional view (partially a side view) of the first coil of the first in-vivo implantation device along its longitudinal direction, illustrating the state in which the first coil is extended in a straight line. [Figure 3] Figure 1 shows a cross-sectional view (partially a side view) of the second coil of the second in-vivo implantation device along its longitudinal direction, illustrating the state in which the second coil is extended in a straight line. [Figure 4] This is a cross-sectional view showing the structure of the fiber layer. [Figure 5] This is a schematic diagram showing the structure of the fibers in a fiber layer. [Figure 6] This is a schematic diagram showing a modified example of the fiber structure shown in Figure 5. [Figure 7] This is a schematic diagram showing an enlarged view of the fiber layer. [Figure 8]It is a schematic diagram of a fiber having a branch portion. [Figure 9] It is a cross-sectional view (partial side view) showing a modified example of the second in-vivo indwelling device shown in FIG. 3. [Figure 10] It is a cross-sectional view (partial side view) showing a modified example of the first in-vivo indwelling device shown in FIG. 2. [Figure 11] It is a cross-sectional view (partial side view) showing another modified example of the second in-vivo indwelling device shown in FIG. 3. [Figure 12] It is a cross-sectional view (partial side view) showing another modified example of the first in-vivo indwelling device shown in FIG. 2. [Figure 13] It is a cross-sectional view (partial side view) showing another modified example of the second in-vivo indwelling device shown in FIG. 3. [Figure 14] It is a cross-sectional view (partial side view) showing yet another modified example of the first in-vivo indwelling device shown in FIG. 2. [Figure 15] It is a cross-sectional view (partial side view) showing yet another modified example of the second in-vivo indwelling device shown in FIG. 3. [Figure 16] It is a cross-sectional view (partial side view) showing yet another modified example of the first in-vivo indwelling device shown in FIG. 2. [Figure 17] It is a cross-sectional view (partial side view) showing yet another modified example of the second in-vivo indwelling device shown in FIG. 3.

Mode for Carrying Out the Invention

[0009] Hereinafter, the present invention will be described more specifically based on the following embodiments. However, the present invention is not limited by the following embodiments, and it is of course possible to appropriately modify and implement it within the range that conforms to the gist of the foregoing and following descriptions, and all of them are included in the technical scope of the present invention. In each drawing, for the sake of convenience, hatching, member numbers, etc. may be omitted, but in such cases, reference shall be made to the specification and other drawings. Also, the dimensions of various members in the drawings may differ from the actual dimensions because priority is given to facilitating the understanding of the features of the present invention.

[0010] The implantation system for an in-vivo device according to this embodiment comprises a first in-vivo device having a first coil and a first fiber layer disposed on the outer surface of the first coil, and a second in-vivo device having a second coil and a second fiber layer disposed on the outer surface of the second coil, wherein the first fiber layer and the second fiber layer each contain fibers containing a polymer material and a drug, and the mass per unit length of the coil of the second fiber layer is less than the mass per unit length of the coil of the first fiber layer. Hereinafter, the implantation system for an in-vivo device may be simply referred to as the system.

[0011] Examples of system use include embolization to promote thrombosis at target sites such as cerebral aneurysms, head and neck aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal artery aneurysms, and abdominal aneurysms. In particular, the system is preferably an in-vivo implantation system for cerebral aneurysms. Aneurysms can be fusiform or saccular in shape.

[0012] Embolization has three phases: Framing, Filling, and Finishing. The first and second coils of the implantation system can each be used in one of the phases, or they can be used across two or three phases. Preferably, the first coil is used for Framing and / or Filling. Preferably, the second coil is used for Finishing.

[0013] The system according to the embodiment will be described with reference to Figures 1 to 17. Figure 1 is a schematic diagram of the implantation system of the in-vivo implantation device according to the embodiment. Figure 2 is a cross-sectional view (partially a side view) along the longitudinal direction of the first coil of the first in-vivo implantation device shown in Figure 1, showing the first coil extended in a straight line. Figure 3 is a cross-sectional view (partially a side view) along the longitudinal direction of the second coil of the second in-vivo implantation device shown in Figure 1, showing the second coil extended in a straight line. Figure 4 is a cross-sectional view showing the structure of the fiber layer. Figure 5 is a schematic diagram showing the fiber structure of the fiber layer. Figure 6 is a schematic diagram showing a modified example of the fiber structure shown in Figure 5. Figure 7 is a schematic diagram of an enlarged view of the fiber layer. Figure 8 is a schematic diagram of a fiber having a branched portion. Figure 9 is a cross-sectional view (partially a side view) showing a modified example of the second in-vivo implantation device shown in Figure 3. Figure 10 is a cross-sectional view (partially a side view) showing a modified example of the first in-vivo implantation device shown in Figure 2. Figure 11 is a cross-sectional view (partially a side view) showing another modified example of the second in-vivo implant shown in Figure 3. Figure 12 is a cross-sectional view (partially a side view) showing another modified example of the first in-vivo implant shown in Figure 2. Figure 13 is a cross-sectional view (partially a side view) showing another modified example of the second in-vivo implant shown in Figure 3. Figure 14 is a cross-sectional view (partially a side view) showing yet another modified example of the first in-vivo implant shown in Figure 2. Figure 15 is a cross-sectional view (partially a side view) showing yet another modified example of the second in-vivo implant shown in Figure 3. Figure 16 is a cross-sectional view (partially a side view) showing yet another modified example of the first in-vivo implant shown in Figure 2. Figure 17 is a cross-sectional view (partially a side view) showing yet another modified example of the second in-vivo implant shown in Figure 3. In Figure 1, the fiber layer is omitted to facilitate understanding of the shape of the secondary coil. Although Figures 14 to 17 show only the coil and fiber layer, it is preferable that other components are arranged as in Figures 2 to 3. As can be seen from Figures 1 to 3, the system 100 comprises a first in-vivo implantation device 1 having a first coil 101 and a first fiber layer 301, and a second in-vivo implantation device 2 having a second coil 102 and a second fiber layer 302. Hereafter, the first in-vivo implantation device 1 may be referred to as the first implantation device 1, and the second in-vivo implantation device 2 may be referred to as the second implantation device 2.

[0014] In the following, when describing a configuration common to the first coil 101 and the second coil 102, they or each may simply be referred to as coils. Thus, when describing a configuration common to the two components, it means that such a configuration may be taken "in the first retaining device 1 and / or the second retaining device 2." That is, only the first retaining device 1 may have the configuration described, only the second retaining device 2 may have the configuration, or both the first retaining device 1 and the second retaining device 2 may have the configuration.

[0015] As can be seen from Figures 2 and 3, the coil 10 preferably has a longitudinal direction x, a radial direction y, and a circumferential direction z. The longitudinal direction x can also be called the longitudinal axis direction. The coil 10 preferably has a distal end and a proximal end in the longitudinal direction x. The proximal side of the coil 10 refers to the direction toward the user or operator's hand with respect to the longitudinal direction x of the coil 10, and the distal side refers to the opposite direction from the proximal side, i.e., the direction toward the treatment target. In Figures 2 and 3, the right side of the figure is the proximal side, and the left side of the figure is the distal side. The radial direction y of the coil 10 refers to the radial direction of the coil 10, and in the radial direction y, inward refers to the direction toward the center of the longitudinal axis of the coil 10, and outward refers to the direction extending radially from the center of the longitudinal axis on the opposite side from the inward direction. The circumferential direction z of the coil 10 refers to the direction around the longitudinal axis. In the following, when the length of each component of the coil 10 is divided into two equal parts in the longitudinal direction x, the proximal side may be referred to as the proximal portion, and the distal side as the distal portion.

[0016] In the longitudinal direction x, the lengths of the first coil 101 and the second coil 102 may be the same or different. In the longitudinal direction x, the second coil 102 may be longer than the first coil 101. In the longitudinal direction x, the first coil 101 may be longer than the second coil 102.

[0017] As shown in Figures 1 and 2, the first coil 101 is preferably composed of a first wire 211. As shown in Figures 1 and 3, the second coil 102 is preferably composed of a second wire 212. Hereafter, when describing the common components of the first wire 211 and the second wire 212, they or each may simply be referred to as wires.

[0018] A coil is constructed by winding one or more wires in a spiral shape. Preferably, a coil is constructed by winding a long wire. Examples of wires include solid wire, stranded wire, and coiled wire, with solid wire being preferred. It is also preferable that the wire is not a coiled wire. Preferably, the first wire 211 and the second wire 212 are both solid wires.

[0019] A coil constructed by winding a wire in a spiral shape is sometimes called a primary coil. A secondary coil is sometimes formed by further shaping a primary coil into a spiral or three-dimensional shape. Unless otherwise specified in this specification, coils refer to the configuration in the state of a primary coil. It is preferable that a primary coil, as shown in Figures 2 and 3, is shaped to form a secondary coil as shown in Figure 1.

[0020] The wire is preferably biocompatible and flexible. Examples of materials constituting the wire include platinum, gold, titanium, tungsten and their alloys, stainless steel, and other metallic materials or combinations thereof. Among these, it is more preferable that the wire be composed of a platinum-tungsten alloy.

[0021] The wire has a longitudinal axis and a distal end and a proximal end along the longitudinal axis. The wire may be composed of a single linear member from the distal end to the proximal end, or it may be composed of multiple linear members connected to each other along the longitudinal axis. The shape of the cross-section perpendicular to the longitudinal axis of the wire may be circular, oval, polygonal, or a combination thereof. The shape of the cross-section perpendicular to the longitudinal axis of the wire may be the same along the entire longitudinal axis of the wire, or it may differ depending on the position along the longitudinal axis.

[0022] The outer diameter of the wire is not particularly limited, but may be, for example, 25 μm or more, 30 μm or more, or 35 μm or more, and may be 75 μm or less, or 70 μm or less.

[0023] The outer diameters of the first wire 211 and the second wire 212 may be the same. Alternatively, the outer diameters of the first wire 211 and the second wire 212 may be different. The outer diameter of the first wire 211 may be larger than that of the second wire 212, so that the first coil 101 is more likely to be rigid than the second coil 102. However, the outer diameter of the first wire 211 may be smaller than that of the second wire 212.

[0024] The outer diameter of the wire may be the same along its longitudinal axis, or it may vary depending on its position along the longitudinal axis. If the cross-section of the wire is not circular, the outer diameter of the wire shall refer to the equivalent circular diameter.

[0025] As shown in Figure 2, the first coil 101 has an outer circumferential surface 121. Preferably, the first coil 101 has an inner circumferential surface 131. The surface of the first coil 101 includes the outer circumferential surface 121 and the inner circumferential surface 131. Preferably, the first coil 101 has a lumen 111 extending in the longitudinal direction x. The outer circumferential surface 121 of the first coil 101 faces the outside of the first coil 101, i.e., the outside in the radial direction y, and the inner circumferential surface 131 of the first coil 101 faces the lumen 111. Preferably, the first stretch resistance member 501 is disposed in the lumen 111.

[0026] As shown in Figure 3, the second coil 102 has an outer circumferential surface 122. Preferably, the second coil 102 has an inner circumferential surface 132. The surface of the second coil 102 includes the outer circumferential surface 122 and the inner circumferential surface 132. Preferably, the second coil 102 has a lumen 112 extending in the longitudinal direction x. The outer circumferential surface 122 of the second coil 102 faces the outside of the second coil 102, i.e., the outside in the radial direction y, and the inner circumferential surface 132 of the second coil 102 faces the lumen 112. Preferably, a second stretch resistance member 502 is disposed in the lumen 112.

[0027] The coil may be a single-layer coil or a multi-layer coil having multiple layers. A portion of the coil in the longitudinal direction x may be single-layered, while the remaining portion is multi-layered.

[0028] The coil density, or winding spacing, is not particularly limited and can be tightly wound, pitched, or a combination of both. The coil may have adjacent wires in contact along a portion of its longitudinal direction x, or adjacent wires may be in contact along its entire longitudinal direction x. When adjacent wires are in contact along the longitudinal direction x of the coil, it is called tightly wound; when they are not in contact, it is called pitched. The state of not being in contact means that there is a gap between adjacent wires along the longitudinal direction x of the coil. It is preferable that the first coil 101 and the second coil 102 are both tightly wound coils, but at least one of the first coil 101 and the second coil 102 may be a pitched coil.

[0029] The outer edge shape of the cross-section perpendicular to the longitudinal direction x of the coil may be circular, oval, polygonal, or a combination thereof. The oval shape includes elliptical, egg-shaped, and rounded rectangular shapes. The same applies in the following description.

[0030] The surface of the coil may have an uneven structure, for example, if the cross-sections of adjacent wires in the longitudinal direction x of the coil are circular or elliptical.

[0031] The maximum and minimum outer diameters of the coil are not particularly limited and can be appropriately selected according to the phase of the procedure. For example, they may be 150 μm or more, 180 μm or more, or 200 μm or more, and may be 400 μm or less, 380 μm or less, or 350 μm or less.

[0032] The outer diameters of the first coil 101 and the second coil 102 may be the same. Alternatively, the outer diameters of the first coil 101 and the second coil 102 may be different. The outer diameter of the first coil 101 may be smaller than that of the second coil 102, so that the first coil 101 tends to be stiffer than the second coil 102. However, the outer diameter of the first coil 101 may be larger than that of the second coil 102. Here, the outer diameters of the first coil 101 and the second coil 102 refer to the average values ​​of the outer diameters in the longitudinal direction x of the coils.

[0033] The outer diameter and / or inner diameter of the coil may be the same size along the longitudinal direction x of the coil, or they may be different sizes depending on the position along the longitudinal direction x of the coil. If the cross-section of the coil is not circular, the outer diameter of the coil shall refer to the equivalent circular diameter. Similarly, if the inner lumen cross-section of the coil is not circular, the inner diameter of the coil shall refer to the equivalent circular diameter.

[0034] The outer diameter of the coil may be constant along its longitudinal direction x. A constant outer diameter means that the outer diameter of the coil is substantially constant throughout its entire longitudinal direction x, and includes cases where the change in the outer diameter of the coil over its entire longitudinal direction x is within ±5%.

[0035] Although not shown in the diagram, the coil may have a transition section in which the outer diameter decreases toward the distal end. This allows the flexibility of the coil to gradually increase from the distal end toward the proximal end. In the transition section, the outer diameter of the coil may decrease in a tapered manner toward the distal end. Here, tapered means that the outer diameter of the wire constituting the coil decreases with each turn, resulting in a tapered envelope of the coil's outer diameter in the transition section. In the transition section, the outer diameter of the coil may decrease in a stepped manner toward the distal end. Here, stepped means that the outer diameter of the wire constituting the coil decreases at least every two or more turns.

[0036] When a coil is divided into two equal parts, a distal part and a proximal part, along its longitudinal direction x, the average outer diameter of the proximal part of the coil may be smaller than the average outer diameter of the distal part. A smaller outer diameter in the proximal part increases the flexibility of the proximal part of the coil, thus ensuring ease of handling.

[0037] As shown in Figure 2, the first retainer 1 has a first fiber layer 301 arranged on the outer circumferential surface 121 of the first coil 101. As shown in Figure 3, the second retainer 2 has a second fiber layer 302 arranged on the outer circumferential surface 122 of the second coil 102. As can be seen from Figures 4 to 7, the first fiber layer 301 contains fibers 40 containing a polymer material 41 and a drug 42. The second fiber layer 302 also contains fibers 40 containing a polymer material 41 and a drug 42. Hereafter, when describing the common structure of the first fiber layer 301 and the second fiber layer 302, they or each may simply be referred to as fiber layers.

[0038] In system 100, the first fiber layer 301 and the second fiber layer 302 each contain fibers 40 containing a polymer material 41 and a drug 42, respectively. This prevents the drug 42 from detaching from the coil early in the procedure and enhances the sustained release of the drug compared to when the drug is applied to the coil surface.

[0039] The fiber layer may be arranged on only a portion of the outer surface of the coil, or it may be arranged on the entire outer surface of the coil. The fiber layer may be arranged on the inner surface of the coil. The fiber layer may be arranged on only a portion of the inner surface of the coil, or it may be arranged on the entire inner surface of the coil.

[0040] As shown in Figures 2 to 4, the fiber layer preferably has a cylindrical shape arranged along the peripheral wall of the coil. The fiber layer preferably has a cylindrical shape with only one lumen. It is preferable that the axis center in the longitudinal direction x of the coil coincides with the axis center in the longitudinal direction of the cylindrical fiber layer.

[0041] As shown in Figures 2 and 4, when the first fiber layer 301 has a cylindrical shape, it is preferable that the first fiber layer 301 has an outer peripheral surface 321 facing outward from the first implantation device 1 and an inner peripheral surface 331 facing toward the outer peripheral surface 121 of the first coil 101. It is preferable that the first fiber layer 301 has a lumen 311, and that the first coil 101 is disposed in the lumen 311. It is preferable that the first fiber layer 301 has a distal end 341 and a proximal end 351 in the longitudinal direction x.

[0042] As shown in Figures 3 and 4, when the second fiber layer 302 has a cylindrical shape, it is preferable that the second fiber layer 302 has an outer peripheral surface 322 facing outward from the second implantation device 2 and an inner peripheral surface 332 facing toward the outer peripheral surface 122 of the second coil 102. It is preferable that the second fiber layer 302 has a lumen 312, and that the second coil 102 is disposed in the lumen 312. It is preferable that the second fiber layer 302 has a distal end 342 and a proximal end 352 in the longitudinal direction x.

[0043] As can be seen from Figures 2 and 3, it is preferable that the inner surface of the fiber layer is in contact with the outer surface of the coil. It is preferable that no other members are placed between the coil and the fiber layer in the radial direction y. For example, it is preferable that no chemicals are applied to the outer surface of the coil in any form other than the fiber layer.

[0044] The fiber layer may consist of a single layer or multiple layers.

[0045] The fiber layer may be fixed to the coil. The method of fixation is not particularly limited and may include suturing, bonding, welding, clamping, etc. The fiber layer may be fixed to the coil by a portion of the fiber layer being sandwiched between two wires that make up the coil. The fiber layer may be fixed by bonding or welding the inner surface of the fiber layer to the outer surface of the coil.

[0046] In the fiber layer, the fibers 40 may be wound around the outer surface of the coil. That is, in the fiber layer, the fibers 40 may be wound around an axis in the longitudinal direction x of the coil.

[0047] The coil may have only one fiber layer or multiple fiber layers. For example, one or more fiber layers may be arranged in the distal and proximal parts of the coil. Preferably, the multiple fiber layers are arranged in the longitudinal direction x. The multiple fiber layers may be separated from each other or in contact in the longitudinal direction x. Preferably, all of the multiple fiber layers have a tubular shape.

[0048] As shown in image 60 in Figure 7, the first fiber layer 301 and the second fiber layer 302 contain fibers 40. Generally, fibers are thin, thread-like substances, but in this specification, fibers 40 refer to those with an average fiber diameter of 100 μm or less, and those with an average fiber diameter exceeding 100 μm are excluded. The average fiber diameter of fibers 40 can be measured by the following method: Obtain an image of the fibers at a magnification of 1000x using a scanning electron microscope or laser microscope (for example, a scanning transmission electron microscope (STEM-EDX / EELS) HD-2700 manufactured by Hitachi High-Technologies Corporation). The arithmetic mean of the diameters of at least 20 fibers measured in the obtained image is taken as the average fiber diameter of fibers 40. When measuring the fiber diameter, if the cross-sectional shape of the fiber is not circular, the average of the diameters of the circumscribed and inscribed circles of the irregular cross-section is taken as the fiber diameter.

[0049] As shown in Figures 5 and 6, the first fiber layer 301 and the second fiber layer 302 contain fibers 40 containing a polymer material 41 and a drug 42. Therefore, compared to the case where the drug is applied to the coil surface, it is possible to prevent the drug from falling off the coil at an early stage of the procedure and to improve the sustained release of the drug.

[0050] As the fiber layer, a sheet-like or tubular fiber assembly composed of fibers 40 can be used. The fiber assembly may be a knitted fabric, woven fabric, nonwoven fabric, etc., formed from the fibers 40, and the nonwoven fabric may be a dry-laid or wet-laid nonwoven fabric. In the fiber assembly, the fibers 40 may be joined to each other physically, chemically, or mechanically. In the fiber layer, the fibers 40 may be joined to each other by entanglement, or they may be joined by heat fusion.

[0051] The fiber layer may consist of one or more fibers 40. The fibers 40 may be composed of fiber bundles of multiple fibers. The form of the fiber bundle is not particularly limited and may be twisted, untwisted, or untwisted. The number of fibers in the fiber bundle may be, for example, two to ten.

[0052] The fiber layer may be composed of only one type of fiber 40. For example, the fiber layer may be composed only of fibers containing a biodegradable polymer material and a drug, or it may be composed only of fibers containing a non-biodegradable polymer material and a drug.

[0053] The fiber layer may be composed of multiple types of fibers 40. For example, the fiber layer may be composed of a first fiber containing a biodegradable polymer material and a drug, and a second fiber containing a non-biodegradable polymer material and a drug.

[0054] The fiber 40 may be a hollow fiber, but it is preferable that it be a solid fiber. The fiber 40 may or may not have crimp. A crimped fiber is, for example, a solid fiber having a spiral-shaped three-dimensional crimp structure.

[0055] A single fiber 40 may have a straight, linear shape, or it may have a branched shape, as shown in Figure 8. Figure 8 shows an example in which the fiber 40 has a branched portion 46, and the branched portion 46 has a first branch 46a and a second branch 46b.

[0056] The fiber layer may stretch in the radial direction y. For example, as the coil expands, the fiber layer may stretch in the radial direction y.

[0057] The average fiber diameter of fiber 40 is preferably 1 nm or more, 10 nm or more, 100 nm or more, or 1 μm or more. In order to prevent the outer diameter of the fiber layer from becoming excessively large, the average fiber diameter of fiber 40 is preferably 50 μm or less, 45 μm or less, or 40 μm or less.

[0058] The average fiber length of fiber 40 may be, for example, 100 mm or more, 200 mm or more, 300 mm or more, or 1300 mm or less, 1200 mm or less, 1100 mm or less, or 1000 mm or less.

[0059] (Method for measuring the average fiber length of a fiber) Ten individual fibers are taken from the fiber layer 30. Each fiber is straightened without stretching, and its length (mm) is measured on a measuring scale. The average of the measured lengths of the ten fibers is taken as the average fiber length of fiber 40. If the number of fibers constituting the fiber layer is less than ten, the length of all the fibers constituting the fiber layer is measured, and the average of the measured lengths of the multiple fibers is taken as the average fiber length of fiber 40. If the number of fibers constituting the fiber layer is one, the length of that one fiber is taken as the average fiber length of fiber 40. As shown in Figure 8, if the fiber 40 to be measured has a branching section 46, and for example the branching section 46 has a first branch 46a and a second branch 46b, the longer of the first branch 46a and the second branch 46b (first branch 46a in Figure 8) is used to calculate the fiber length.

[0060] The fibers 40 can be formed using, for example, electrospinning, melt spinning, wet spinning, or dry spinning, and among these, it is preferable to form them using electrospinning. When forming a fiber layer using electrospinning, a coil can be used as a collector in the electrospinning system, and the fibers 40 can be wound around the outer surface of the coil by spinning while rotating the coil.

[0061] The fiber layer preferably does not contain any materials other than the fibers 40, such as thread-like materials with an average fiber diameter of more than 100 μm, resin wires, metal wires, etc.

[0062] Preferably, the fiber layer is composed only of fibers 40 containing a polymer material 41 and a drug 42.

[0063] The polymer contained in polymer material 41 may be a synthetic polymer or a natural polymer. Polymer material 41 also includes resins.

[0064] The polymer material 41 contained in the fiber 40 is preferably a biodegradable polymer material. As the biodegradable material decomposes, the surface area of ​​the fiber 40 tends to increase, making it easier to release the drug 42 contained in the fiber 40. In this specification, a biodegradable polymer material refers to a material that has the property of being hydrolyzed in the body environment and, after decomposition, becomes a non-toxic low-molecular-weight substance that is metabolized.

[0065] The polymers contained in biodegradable polymer materials may be synthetic polymers or natural polymers, but synthetic polymers are preferred. Biodegradable polymer materials also include biodegradable resins. Examples of biodegradable polymer materials include polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), glycolic acid-lactide copolymer (PLGA), glycolic acid-ε-caprolactone copolymer, lactide-ε-caprolactone copolymer, glycolic acid-lactide-ε-caprolactone copolymer, poly(p-dioxanone) (PDO), poly(2-oxetanone), polymalic acid, polyhydroxyalkanoic acid (PHA), polyhydroxybutyrate (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PH Examples of these substances include, but are not limited to, BV, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH), starches (carboxymethyl starch, dialdehyde starch), celluloses (CMC, MC, HEC, HPC), proteins (collagen, gelatin, glue, mixture of collagen and elastin), polysaccharides (glycosaminoglycans, chitin, chitosan, hyaluronic acid), gums (acacia gum, guar gum, tragacanth gum), fibroin, laminin, casein, polypeptides, tannins, lignin, alginic acid, etc. These may be used individually or in combination of two or more.

[0066] The polymer material 41 contained in the fiber 40 may be a non-biodegradable polymer material. This makes it less likely to decompose compared to the case of a biodegradable material, thus delaying the release timing of the drug 42 contained in the fiber 40. In this specification, a non-biodegradable polymer material refers to a material other than a biodegradable polymer material that is resistant to hydrolysis in the internal environment of the body.

[0067] The polymers contained in non-biodegradable polymer materials may be synthetic polymers or natural polymers, but synthetic polymers are preferred. Non-biodegradable polymer materials also include non-biodegradable resins. Examples of non-biodegradable polymer materials include, but are not limited to, vinyl acetate such as ethylene vinyl acetate, polyolefins such as polyethylene and polypropylene, polyesters such as polyethylene terephthalate, polyamides such as nylon, fluorine such as polyvinylidene fluoride and polytetrafluoroethylene, vinyl chloride such as acrylic and polyvinyl chloride, polycarbonate, epoxy, polyurethanes such as polyurethane elastomers, polyacrylonitrile, keratin, and silk fibroin. These may be used individually or in combination of two or more.

[0068] In addition to the materials mentioned above, the polymer material 41 may also contain various additives such as plasticizers, pigments, flame retardants, antistatic agents, lubricants, softeners, surfactants, and antibacterial agents.

[0069] The drug 42 contained in the fiber 40 may be the active ingredient (API) alone, or it may be a mixture with other additives. Preferred additives include base materials, plasticizers, stabilizers, surfactants, and the like.

[0070] The type of drug 42 contained in the fiber 40 is not particularly limited as long as it is necessary for the prevention or treatment of the affected area. Preferably, the drug 42 has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, vasoconstriction inhibitory effect, anticoagulant effect, and shear stress sensing inhibitory effect, and more preferably, it has at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, and vasoconstriction inhibitory effect. Examples of drugs include selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, sertraline, paroxetine, etc.), DPP-4 inhibitors (sitagliptin, linagliptin, alogliptin, etc.), HMG-CoA reductase inhibitors (atorvastatin, pitavastatin, rosuvastatin, pravastatin, simvastatin, fluvastatin, lovastatin, mevastatin, cerivastatin, etc.), nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, naproxen, celecoxib, etc.), angiotensin II receptor blockers (ARBs) (losartan, valsartan, telmisartan, etc.), tocopherol acetate (vitamin E acetate, eviprostat, estrol, etc.), ascorbic acid (Asconal, Cinal, Cefylol), and edaravone (Radicut, Free Radical Scavenger). (e.g., jaber), N-acetyl-L-cysteine ​​(NAC), calcium channel blockers (amlodipine, nifedipine, diltiazem, etc.), diuretics (furosemide, trichlormethiazide, spironolactone, etc.), angiotensin-converting enzyme inhibitors (ACE inhibitors) (enalapril, lisinopril, perindopril, etc.), beta-blockers (metoprolol, atenolol, bisoprolol, etc.), alpha-blockers (prazosin, terazosin, doxamylase). Examples include zosyn, alpha-beta blockers (carvedilol, labetalol, butoxamine, etc.), nitrates (nitroglycerin, isosorbide dinitrate, etc.), prostacyclin analogs (epoprostenol, treprostinil, etc.), anticoagulants (heparin, heparin derivatives, warfarin, antithrombin drugs such as dabigatran, rivaroxaban, etc.), and antiplatelet agents (aspirin, clopidogrel, ticagrelor, etc.).

[0071] The drug 42 may be encapsulated in a capsule. The size of the capsule is preferably 10 nm or larger, more preferably 50 nm or larger, even more preferably 100 nm or larger, and preferably 500 nm or smaller, more preferably 400 nm or smaller, and even more preferably 200 nm or smaller. The capsule is preferably made of a biodegradable material. As the biodegradable material, bioabsorbable polymers, natural polymers, decellularized biological tissues or cells, or combinations thereof can be used. As bioabsorbable polymers, at least one of polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolic acid (PGA), copolymer of lactic acid and glycolic acid (PLGA), polycaprolactone (PCL), and polydioxanone (PDS) is preferably used. As natural polymers, at least one of collagen, laminin, fibroin, gelatin, glycosaminoglycan, chitin, chitosan, hyaluronic acid, and polypeptide is preferably used.

[0072] The fiber layer may contain biodegradable materials other than the polymer material 41. Examples of such materials include biodegradable alloys such as magnesium alloys and iron-manganese alloys. A portion of the fiber 40 may be composed of a biodegradable alloy.

[0073] The fiber 40 may contain an X-ray opaque material. For example, the X-ray opaque material may be coated on the surface of the fiber 40, embedded within the fiber 40, or retained within the fiber 40. Examples of X-ray opaque materials include lead, barium, iodine, tungsten, gold, silver, platinum, iridium, platinum-iridium alloy, stainless steel, titanium, cobalt-chromium alloy, palladium, and tantalum.

[0074] In addition to the materials mentioned above, the fiber 40 may also contain various additives such as plasticizers, pigments, flame retardants, antistatic agents, lubricants, softeners, and surfactants.

[0075] As shown in Figure 5, it is preferable that the polymer material 41 and the drug 42 are mixed in the fiber 40. In the fiber 40, the drug 42 may be dispersed in the polymer material 41. The drug 42 may be uniformly dispersed in the polymer material 41, or it may be locally dispersed. The drug 42 may be dispersed in the polymer material 41 in particulate form. The drug 42 may be exposed on the surface of the fiber 40, or it may be present only inside the fiber 40. In the fiber 40, the polymer material 41 may function as a matrix. In the fiber 40, the drug 42 may be dissolved in the polymer material 41.

[0076] The fiber 40 shown in Figure 5 can be produced, for example, by mixing (preferably kneading) a polymer material and a chemical agent. For production, a spinning system equipped with an extruder and a spinneret may be used, for example. The polymer material and chemical agent are mixed (preferably kneaded) in the extruder, the mixture is melted, and the mixture is extruded from the spinneret to produce the fiber.

[0077] In the fiber 40, the mixing ratio of polymer material 41 to drug 42 is preferably 1 / 1 or more by mass, more preferably 2 / 1 or more, even more preferably 3 / 1 or more, and also preferably 100 / 1 or less, more preferably 80 / 1 or less, and even more preferably 50 / 1 or less.

[0078] In the fiber 40, the content of the polymer material 41 is preferably 20 wt% or more, more preferably 30 wt% or more, even more preferably 40 wt% or more, and also preferably 80 wt% or less, more preferably 70 wt% or less, and even more preferably 60 wt% or less.

[0079] In the fiber 40, the content of the agent 42 is preferably 20 wt% or more, more preferably 30 wt% or more, even more preferably 40 wt% or more, and also preferably 80 wt% or less, more preferably 70 wt% or less, and even more preferably 60 wt% or less.

[0080] In the fiber 40, when the drug 42 is dispersed in particulate form within the polymer material 41, the particle size is not particularly limited, but may be, for example, 10.0 nm or larger, 50.0 nm or larger, 100 nm or larger, or 200 nm or larger. Alternatively, the particle size may be 5.00 μm or smaller, 4.00 μm or smaller, 3.00 μm or smaller, 2.00 μm or smaller, or 1.00 μm or smaller. Having the particle size within the above range makes it easier to uniformly disperse the particulate drug 42 in the polymer material 41, and also facilitates the manufacture of the fiber 40. Here, "particle size" refers to the volume-average particle size (D50) at the median 50% diameter in the particle size distribution obtained by dynamic light scattering or the like. Commercially available particulate drugs may be used, in which case the particle size listed in the catalog can be adopted.

[0081] The fiber 40 may be a composite fiber having a core-sheath structure, a side-by-side structure, or a sea-island structure. The core-sheath structure includes concentric core-sheath types and eccentric core-sheath types. In order to slow down the release rate of the active ingredient of the drug 42 from the fiber 40, it is preferable that the drug 42 is encapsulated in the polymer material 41 in the fiber 40. Encapsulating the drug 42 in the polymer material 41 means that the drug 42 is covered by the polymer material 41 and the drug 42 is not exposed to the outside. By covering the drug 42 with the polymer material 41, the occurrence of an initial burst of the drug 42 can be suppressed, and the release rate of the active ingredient of the drug 42 can be easily controlled.

[0082] As shown in Figure 6, the fiber 40 preferably includes a core-sheath type fiber having a core portion 44 and a sheath portion 45, and more preferably consists of a core-sheath type fiber. In that case, it is preferable that the core portion 44 contains the drug 42 and the sheath portion 45 contains a polymer material 41. By using a composite fiber of this shape, it becomes easier to suppress the occurrence of an initial burst of the drug 42 and to control the release rate of the active ingredient of the drug 42.

[0083] If the fiber 40 is a core-sheath type fiber having a core portion 44 and a sheath portion 45, and the fiber 40 is branched into a first branch portion 46a and a second branch portion 46b, then the core portion 44 may be exposed in the first branch portion 46a and / or the second branch portion 46b without being covered by the sheath portion 45.

[0084] In the core portion 44, the content of the polymer material 41 is preferably 20 wt% or less, more preferably 10 wt% or less, even more preferably 5 wt% or less, and it is even more preferable that the core portion 44 does not contain the polymer material 41.

[0085] In the sheath portion 45, the content of the drug 42 is preferably 20 wt% or less, more preferably 10 wt% or less, even more preferably 5 wt% or less, and it is even more preferable that the sheath portion 45 does not contain the drug 42.

[0086] The fiber layer preferably consists of one or more core-sheath type fibers.

[0087] To facilitate control of the release rate of the active ingredient in the drug, a concentric core sheath type structure is preferred for the composite fiber.

[0088] The core-sheath type fiber contained in fiber 40 can be manufactured in the same manner as general core-sheath type fibers. For manufacturing, for example, an electrospinning system equipped with a spinneret and collector having a multi-tube shape may be used. Preferably, the core material supplied to the system contains a drug 42, and the sheath material contains a polymer material 41. The core material may contain a solvent that is soluble in the drug 42. The sheath material may also contain a solvent that is soluble in the polymer material 41. The solvent is not particularly limited as long as it can dissolve the polymer material 41 and / or the drug 42 and can be sprayed from the spinneret. Examples of solvents include water, N,N-dimethylformamide (DMF), ethanol, acetone, tetrahydrofuran, chloroform, dichloromethane, ethyl acetate, toluene, and the like.

[0089] In system 100, the mass per unit length of the second fiber layer 302 is less than the mass per unit length of the first fiber layer 301. Although adding a fiber layer to the coil surface tends to make the coil stiffer, the second fiber layer 302 has less mass per unit length than the first fiber layer 301, allowing the second coil 102 to be more flexible than the first coil 101. Therefore, by introducing the second coil 102 into the body after the first coil 101, it becomes easier to locate empty spaces within the tumor using the first coil 101 and to place the first coil 101 deep within the tumor, thereby preventing the first coil 101 from straying outside the tumor. Furthermore, after the placement of the first coil 101, it becomes easier to fold and pack the second coil 102 into the tumor.

[0090] The mass M1 per unit length of the coil of the first fiber layer 301 can be expressed by the following equation (1). The mass M2 per unit length of the coil of the second fiber layer 302 can be expressed by the following equation (2). M1 = m1 (mg) / L1 (mm) ... (1) M1 = m² (mg) / L² (mm) ... (2) Here, m1 is the total mass of the first fiber layer 301, L1 is the total length of the first fiber layer 301 in the longitudinal direction x when the first fiber layer 301 is arranged in the first coil 101, m2 is the total mass of the second fiber layer 302, and L2 is the total length of the second fiber layer 302 in the longitudinal direction x when the second fiber layer 302 is arranged in the second coil 102. Figure 2 shows L1 and Figure 3 shows L2.

[0091] The mass M1 per unit length of the first fiber layer 301 and the mass M2 per unit length of the second fiber layer 302 can be measured by the following method. (Measurement of the mass of the fiber layer per unit length of the coil) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), lengths L1 and L2 are measured using a straight ruler (Shinwa Measuring Instruments Co., Ltd., model 13005). The first coil 101 and the first fiber layer 301 are immersed in deionized water, and the first fiber layer 301 arranged on the first coil 101 is scraped off using a blade such as a razor. By scraping the first fiber layer 301 from the first coil 101 in deionized water so as to remove fragments of the fibers 40 of the first fiber layer 301, it is possible to prevent the fibers 40 from becoming airborne and to prevent mass loss. The second fiber layer 302 arranged on the second coil 102 is scraped off in the same manner. The total mass m1 of the first fiber layer 301 and the total mass m2 of the second fiber layer 302 are measured using a precision electronic balance (Mettler Toledo, model XPR2U). Determine M1 from the measured m1 and L1. Determine M2 from the measured m2 and L2.

[0092] The mass of the second fiber layer 302 per coil unit length is preferably 1 / 2 or less, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less, of the mass of the first fiber layer 301 per coil unit length. The mass of the second fiber layer 302 per coil unit length may be 1 / 1000 or more, 1 / 500 or more, or 1 / 100 or more, of the mass of the first fiber layer 301 per coil unit length. By setting the mass of the second fiber layer 302 in this way, the flexibility of the second coil 102 is maintained, so that the second coil 102 can be placed in the knot while ensuring operability.

[0093] Preferably, the mass of the first fiber layer 301 per unit length of the coil decreases from the distal end to the proximal end of the first coil 101. Preferably, the mass of the second fiber layer 302 per unit length of the coil decreases from the distal end to the proximal end of the second coil 102.

[0094] Bulk density of fiber layer 30 BD (g / cm³) 3 ) is the basis weight W (g / m 2 This is the value obtained by dividing ) by the thickness T (mm). Specifically, the bulk density BD1 of the first fiber layer 301 can be determined from the following equations (3) and (4). The bulk density BD2 of the second fiber layer 302 can be determined from the following equations (5) and (6). BD1 = W1 / T1 ... (3) W1 = m1 / A1 ... (4) BD2 = W2 / T2 ... (5) W2 = m2 / A2 ... (6) Here, W1 is the basis weight of the first fiber layer 301, T1 is the thickness of the first fiber layer 301, A1 is the area of ​​the first fiber layer 301, W2 is the basis weight of the second fiber layer 302, T2 is the thickness of the second fiber layer 302, and A2 is the area of ​​the second fiber layer 302.

[0095] (Method for measuring the basis weight of a fiber layer) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), the area A1 of the first fiber layer 301 and the area A2 of the second fiber layer 302 are measured using a straight ruler (Shinwa Measuring Instruments Co., Ltd., model 13005). Then, m1 and m2 are measured using a precision electronic balance (Mettler Toledo, model XPR2U) in the same manner as described in "Measurement of the mass of the fiber layer per unit length of coil". From the measured m1 and A1, the basis weight W1 of the first fiber layer 301 can be determined. From the measured m2 and A2, the basis weight W2 of the second fiber layer 302 can be determined.

[0096] (Method for measuring the thickness of the fiber layer) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), the first coil 101 with the first fiber layer 301 attached is cut along the radial y direction using 1cm precision nippers (ESD Corporation, model EA535TA-13). Three test specimens with a length of 1cm in the longitudinal x direction of the coil 10 are obtained from the portion including the center of the longitudinal x direction of the first fiber layer 301, the distal end of the longitudinal x direction of the first fiber layer 301, and the proximal end of the first fiber layer 301. These test specimens will be referred to as B1, B2, and B3 below. In the same manner, test specimens C1, C2, and C3 are obtained from the second coil 102 with the second fiber layer 302 attached. The distal cross-section of each test specimen is observed with a microscope (digital microscope) (Keyence Corporation, model VHX-X1), and the average thickness of the fiber layer in each cross-section is measured. The average thickness is obtained by measuring the thickness of the fiber layer at equally spaced points in the circumferential direction of the coil and calculating the average of these thicknesses. Equally spaced points can be, for example, 12 points that are 30° apart within the 360° circumferential direction z of the coil. For example, the average thickness of the distal cross-section of test specimen B1 can be the average of the thicknesses of the fiber layer at 12 equally spaced points in the circumferential direction on the distal cross-section of test specimen B1. The average of the average thicknesses of test specimens B1 to B3 can be taken as the thickness T1 of the first fiber layer 301, and the average of the average thicknesses of test specimens C1 to C3 can be taken as the thickness T2 of the second fiber layer 302.

[0097] The bulk density BDp of the second fiber layer 302 is preferably smaller than the bulk density BDd of the first fiber layer 301. Setting the bulk density in this way makes it easier to maintain the flexibility of the second coil 102.

[0098] The bulk density BDp of the second fiber layer 302 may be 0.1 times or more, 0.2 times or more, 0.3 times or more, and may be 0.9 times or less, 0.8 times or less, or 0.7 times or less, of the bulk density BDd of the first fiber layer 301.

[0099] The bulk density of the fiber layer preferably decreases from the distal end side to the proximal end side of the coil. That is, it is preferably configured such that the gap between the fibers 40 of the fiber layer widens from the distal end side to the proximal end side of the coil. From the distal end side to the proximal end side of the coil, the bulk density of the fiber layer may decrease stepwise or may gradually decrease.

[0100] The bulk density BDd of the first fiber layer 301 preferably decreases from the distal end side to the proximal end side of the first coil 101. The bulk density BDp of the second fiber layer 302 preferably decreases from the distal end side to the proximal end side of the second coil 102.

[0101] The bulk density of the fiber layer is not particularly limited, but it is preferably 10 ng / cm 3 or more, more preferably 50 ng / cm 3 or more, and even more preferably 100 ng / cm 3 or more. Also, the bulk density of the fiber layer is preferably 10000 ng / cm 3 or less, more preferably 5000 ng / cm 3 or less, and even more preferably 1000 ng / cm 3 or less. When the bulk density is 10 ng / cm 3 or more, it becomes easier to hold the amount of drug necessary for treatment by the fiber layer. Also, when the bulk density is 10000 ng / cm 3 or less, the flexibility of the coil is more easily maintained even when the fiber layer is arranged on the coil.

[0102] The basis weight of the second fiber layer 302 is preferably smaller than that of the first fiber layer 301. The basis weight of the second fiber layer 302 is preferably 1 / 2 or less of that of the first fiber layer 301, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less. The basis weight of the second fiber layer 302 per coil unit length may be 1 / 50 or more, 1 / 30 or more, or 1 / 10 or more of the basis weight of the first fiber layer 301 per coil unit length. With such a basis weight of the second fiber layer 302, the flexibility of the second coil 102 is maintained, so that the second coil 102 can be placed in the knot while ensuring maneuverability.

[0103] The basis weight of the fiber layer is not particularly limited, but for example, 100 ng / m 2 More than 1000ng / m 2 More than 10000ng / m 2 It may be greater than or equal to 10,000,000 ng / m 2 Below 2500000ng / m 2 Below 50000ng / m 2 The following is also acceptable.

[0104] The thicknesses of the first fiber layer 301 and the second fiber layer 302 may be the same or different. For example, it is preferable that the thickness of the second fiber layer 302 is thinner than the thickness of the first fiber layer 301. The thickness of the second fiber layer 302 is preferably 1 / 2 or less of the thickness of the first fiber layer 301, more preferably 1 / 3 or less, and even more preferably 1 / 4 or less. The mass of the second fiber layer 302 per unit length of coil may be 1 / 50 or more, 1 / 30 or more, or 1 / 10 or more of the thickness of the first fiber layer 301 per unit length of coil.

[0105] The thickness of the first fiber layer 301 and the second fiber layer 302 is not particularly limited, but may be, for example, 1 μm or more, 5 μm or more, 10 μm or more, or 100 μm or less, 50 μm or less, or 20 μm or less. A fiber layer thickness of 1 μm or more makes it easier to hold the amount of drug necessary for treatment with the fiber layer. Also, a fiber layer thickness of 100 μm or less maintains the flexibility of the coil, so that the coil 10 can be placed in the aneurysm while ensuring maneuverability.

[0106] The polymer material 41 contained in the fibers 40 of the first fiber layer 301 and the polymer material 41 contained in the fibers 40 of the second fiber layer 302 may be the same or different. For example, the polymer material 41 contained in the fibers 40 of the second fiber layer 302 may be a biodegradable polymer material, and the polymer material 41 contained in the fibers 40 of the first fiber layer 301 may be a non-biodegradable polymer material. Alternatively, the polymer material 41 contained in the fibers 40 of the second fiber layer 302 may be a non-biodegradable polymer material, and the polymer material 41 contained in the fibers 40 of the first fiber layer 301 may be a biodegradable polymer material.

[0107] The drug 42 contained in the fibers 40 of the first fiber layer 301 and the drug 42 contained in the fibers 40 of the second fiber layer 302 may be of the same type or different types.

[0108] It is preferable that the decomposition rate of the fibers 40 in the second fiber layer 302 is relatively higher than that of the first fiber layer 301. For example, in such a configuration, if the polymer material 41 contained in the fibers 40 of the first fiber layer 301 and the polymer material 41 contained in the fibers 40 of the second fiber layer 302 are of the same type, it is preferable that the mass per coil unit length of the polymer material 41 contained in the fibers 40 of the second fiber layer 302 is less than the mass per coil unit length of the polymer material 41 contained in the fibers 40 of the first fiber layer 301. Note that the "coil unit length" in "mass per coil unit length of polymer material 41 contained in the fibers 40 of the first fiber layer 301" refers to the length L1 described above, and the "coil unit length" in "mass per coil unit length of polymer material 41 contained in the fibers 40 of the second fiber layer 302" refers to the length L2 described above. The same applies in the following explanation.

[0109] Preferably, the mass per unit length of the first fiber layer 301 located in the proximal portion 101P of the first coil 101 is less than the mass per unit length of the first fiber layer 301 located in the distal portion 101D of the first coil 101. This makes it easier to form the distal portion 101D of the first coil 101 rigidly, and makes it easier to use the distal portion 101D to search for empty space within the aneurysm and place the first coil 101 deep within the aneurysm. As a result, the prolapse of the first coil 101 into the parent vessel can be suppressed. In addition, the first coil 101 can be made more flexible in the proximal portion 101P compared to the distal portion 101D, making it easier to fold and pack the first coil 101 into the aneurysm during the latter half of the placement process.

[0110] The mass per unit length of the first fiber layer 301 located in the proximal portion 101P of the first coil 101 may be 0.1 times or more, 0.2 times or more, 0.3 times or more, and may be 0.9 times or less, 0.8 times or less, or 0.7 times or less, of the mass per unit length of the first fiber layer 301 located in the distal portion 101D of the first coil 101.

[0111] Preferably, the mass per unit length of the second fiber layer 302 located in the proximal portion 102P of the second coil 102 is less than the mass per unit length of the second fiber layer 302 located in the distal portion 102D of the second coil 102. This makes it easier to form the distal portion 102D of the second coil 102 rigidly, and makes it easier to use the distal portion 102D to search for empty space within the aneurysm and place the second coil 102 deep within the aneurysm. As a result, the prolapse of the second coil 102 into the parent vessel can be suppressed. In addition, the second coil 102 can be made more flexible in the proximal portion 102P compared to the distal portion 102D, making it easier to fold and pack the second coil 102 into the aneurysm during the latter half of the placement procedure.

[0112] The mass per unit length of the second fiber layer 302 located in the proximal portion 102P of the second coil 102 may be 0.1 times or more, 0.2 times or more, 0.3 times or more, and may be 0.9 times or less, 0.8 times or less, or 0.7 times or less, of the mass per unit length of the second fiber layer 302 located in the distal portion 102D of the second coil 102.

[0113] Preferably, the mass per unit length of the second fiber layer 302 located in the distal portion 102D of the second coil 102 is less than the mass per unit length of the first fiber layer 301 located in the proximal portion 101P of the first coil 101. This makes the proximal portion 102P of the second coil 102 more flexible than the proximal portion 101P of the first coil 101, making it easier to fold and pack the coil into the tumor during the latter half of the implantation procedure.

[0114] The mass per unit length of the second fiber layer 302 located in the distal portion 102D of the second coil 102 may be 0.1 times or more, 0.2 times or more, 0.3 times or more, and may be 0.9 times or less, 0.8 times or less, or 0.7 times or less, of the mass per unit length of the first fiber layer 301 located in the proximal portion 101P of the first coil 101.

[0115] (Method for measuring the mass per unit length of a coil of the first fiber layer 301 located in the proximal portion 101P or distal portion 101D of the first coil 101, and the second fiber layer 302 located in the proximal portion 102P or distal portion 102D of the second coil 102) Under standard conditions (temperature 23±2℃, relative humidity 50±5%), lengths L3, L4, L5, and L6 are measured using a straight ruler (Shinwa Measuring Instruments Co., Ltd., model number 13005). As shown in Figure 2, L3 is the total length in the longitudinal direction x of the first fiber layer 301 in the portion corresponding to the proximal part 101P when the first fiber layer 301 is arranged on the first coil 101, and L4 is the total length in the longitudinal direction x of the first fiber layer 301 in the portion corresponding to the distal part 101D when the first fiber layer 301 is arranged on the first coil 101. As shown in Figure 3, L5 is the total length in the longitudinal direction x of the second fiber layer 302 in the portion corresponding to the proximal part 102P when the second fiber layer 302 is arranged on the second coil 102, and L6 is the total length in the longitudinal direction x of the second fiber layer 302 in the portion corresponding to the distal part 102D when the second fiber layer 302 is arranged on the second coil 102. At the midpoint 141 in the longitudinal direction x of the first coil 101 and at the midpoint 142 in the longitudinal direction x of the second coil 102, the coils are cut along the radial direction y by 1 cm using precision nippers (ESD, model number EA535TA-13). The first coil 101 is separated into a proximal part 101P and a distal part 101D, with the proximal part 101D designated as test piece D1 and the distal part 101D designated as test piece D2. The second coil 102 is separated into a proximal portion 102P and a distal portion 102D, with the proximal portion 102D designated as test piece E1 and the distal portion 102D as test piece E2. Test piece D1 is immersed in deionized water, and the first fiber layer 301 is scraped off from the proximal portion 101P of the first coil 101 using a razor or other blade. The same procedure is performed for test pieces D2, E1, and E2. The total mass mp1 of the first fiber layer 301 located in the proximal portion 101P is measured using a precision electronic balance (Mettler-Toledo, model XPR2U). The mass Mp1 per unit length of coil of the first fiber layer 301 located in the proximal portion 101P can be determined by mp1 / L3.Similarly, using a precision electronic balance, the total mass md1 of the first fiber layer 301 located in the distal section 101D, the total mass mp2 of the second fiber layer 302 located in the proximal section 102P, and the total mass md2 of the second fiber layer 302 located in the distal section 102D are measured, and the mass per unit length of the coil of the first fiber layer 301 located in the distal section 101D is determined as Md1 = md1 / L4, the mass per unit length of the coil of the second fiber layer 302 located in the proximal section 102P is determined as Mp2 = mp2 / L5, and the mass per unit length of the coil of the second fiber layer 302 located in the distal section 102D is determined as Md2 = md2 / L6.

[0116] As shown in Figure 9, it is preferable that the second fiber layer 302 is arranged only in the distal portion 102D of the second coil 102, and that the second fiber layer 302 is not arranged in the proximal portion 102P of the second coil 102. This makes it possible to make the second coil 102 a coil that can be compactly folded and easily packed into the empty space within the nodule, making it suitable as a coil to be packed into the nodule in the latter half of the procedure (preferably at the end of the procedure).

[0117] If the fiber 40 is a core-sheath type fiber, the ratio of the cross-sectional area of ​​the sheath portion 45 to the total cross-sectional area of ​​the cross-section perpendicular to the longitudinal axis of the fiber 40 is defined as the sheath portion cross-sectional area ratio. If the entirety of the first fiber layer 301 and the entirety of the second fiber layer 302 are composed of core-sheath type fibers having a core portion 44 and a sheath portion 45, it is preferable that the sheath portion cross-sectional area ratio of the fiber 40 in the second fiber layer 302 is smaller than that of the fiber 40 in the first fiber layer 301. This makes it easier to change the rate of drug release from the first fiber layer 301 and the second fiber layer 302, as the decomposition rate of the fiber 40 in the second fiber layer 302 tends to be relatively higher than that of the first fiber layer 301.

[0118] The sheath cross-sectional area ratio of the first fiber layer 301 is obtained by measuring the sheath cross-sectional area ratio of each fiber 40 at the midpoint of the longitudinal axis of 10 fibers 40 arbitrarily selected from the first fiber layer 301, and then calculating the average value of the sheath cross-sectional area ratios of the 10 fibers 40. The cross-sectional image can be observed using a scanning electron microscope or a laser microscope (for example, a scanning transmission electron microscope (STEM-EDX / EELS) HD-2700 manufactured by Hitachi High-Technologies Corporation). The sheath cross-sectional area ratio of the second fiber layer 302 can be determined in the same manner.

[0119] The biodegradable materials contained in the first fiber layer 301 and the second fiber layer 302 may be of the same type. In that case, it is preferable that the mass of the biodegradable material per unit length of coil contained in the fibers 40 of the second fiber layer 302 is greater than the mass of the biodegradable material per unit length of coil contained in the fibers 40 of the first fiber layer 301. This configuration also makes it easier to relatively increase the decomposition rate of the fibers 40 of the second fiber layer 302 compared to the first fiber layer 301.

[0120] The non-biodegradable materials contained in the first fiber layer 301 and the second fiber layer 302 may be of the same type. In that case, it is preferable that the mass of the non-biodegradable material per unit length of coil contained in the fibers 40 of the second fiber layer 302 is less than the mass of the non-biodegradable material per unit length of coil contained in the fibers 40 of the first fiber layer 301. This configuration also makes it easier to relatively increase the decomposition rate of the fibers 40 of the second fiber layer 302 compared to the first fiber layer 301.

[0121] As shown in Figures 1 and 2, the first indwelling device 1 may further include a first pusher 551 positioned proximal to the first coil 101 in the longitudinal direction x of the first coil 101 and pushing the first coil 101 distally, and a first connecting portion 531 connecting the proximal portion 101P of the first coil 101 and the distal portion of the first pusher 551. As shown in Figures 1 and 3, the second indwelling device 2 may further include a second pusher 552 positioned proximal to the second coil 102 in the longitudinal direction x of the second coil 102 and pushing the second coil 102 distally, and a second connecting portion 532 connecting the proximal portion 102P of the second coil 102 and the distal portion of the second pusher 552. Hereafter, when describing the common configuration of the first pusher 551 and the second pusher 552, they or each may simply be referred to as pushers. Furthermore, when describing the common configuration of the first connection part 531 and the second connection part 532, they or each of them may simply be referred to as connection parts.

[0122] A pusher is a rod-shaped or wire-shaped member used to hold a coil and push it distally. A pusher can consist of one or more members. It can be composed of a wire member, a coil member, or a combination thereof. A pusher can be made of a conductive material such as stainless steel.

[0123] The connection part connects the coil and the pusher. Preferably, the connection part has a detachment mechanism that allows the coil to detach from the pusher. Examples of detachment mechanisms include hydraulic, electrical, and mechanical types, and among these, an electrical detachment mechanism is preferred. In the detachment mechanism, it is preferable that the connection part is heated and disconnected by electrical or thermal energy supplied through the pusher, causing the coil to detach from the pusher. In this case, it is preferable that the connection part is heated by a high-frequency current supplied between the distal end of the pusher and the counter electrode.

[0124] The connecting portion preferably contains a material that melts or dissolves upon heating. The connecting portion can be cut by Joule heating. Examples of such materials include synthetic resin materials, and it is preferable to use hydrophilic resins of synthetic polymer substances such as polyvinyl alcohol (PVA), PVA crosslinked polymers, PVA water-absorbing gel freeze-thaw elastomers, and polyvinyl alcohol copolymers.

[0125] The shape of the connecting part is not particularly limited and may be linear, rod-shaped, cylindrical, polygonal prism-shaped, cylindrical, polygonal tube-shaped, frustoconical, frustoconical, or a combination thereof.

[0126] Preferably, a portion of the connecting portion is inserted into the lumen of the coil, and preferably, the distal end of the connecting portion is inserted into the lumen of the coil. Preferably, the proximal end of the connecting portion extends proximally from the proximal end of the coil.

[0127] The outer surface of the connection part may be in contact with the inner surface of the coil, or it may be spaced radially away from the inner surface of the coil in the y direction. Furthermore, a portion of the connection part may be positioned in the gap between adjacent wires 21 in the longitudinal direction x of the coil.

[0128] As shown in Figures 1 and 2, the first indwelling device 1 may have a tip 251 positioned at the distal end of the first coil 101. The first indwelling device 1 may also have a base tip 261 positioned at the proximal end of the first coil 101 to close the proximal end of the first coil 101. As shown in Figures 1 and 3, the second indwelling device 2 may have a tip 252 positioned at the distal end of the second coil 102. The second indwelling device 2 may also have a base tip 262 positioned at the proximal end of the second coil 102 to close the proximal end of the second coil 102. Hereafter, when describing the common configuration of the tip 251 and tip 252, they or each may simply be referred to as the tip . Similarly, when describing the common configuration of the base tip 261 and base tip 262, they or each may simply be referred to as the base tip.

[0129] The tip covers a portion of the wire to prevent the distal end of the wire from directly contacting the inner wall of the body. A portion of the tip may be inserted into the lumen of the coil. The tip may be in contact with the outer surface of the coil or the inner surface of the coil. Preferably, the tip closes off the distal end of the coil.

[0130] A portion of the proximal tip may be inserted into the lumen of the coil. The proximal tip may be in contact with the outer surface of the coil or with the inner surface of the coil. The proximal tip has a lumen, and a portion of the connector, such as the distal end of the connector, may be inserted into the lumen of the proximal tip.

[0131] The tip and / or base tip may be made of metal or resin. Examples of resins include thermoplastic resins and UV-curing resins. For example, ester resins such as epoxy acrylate resins, urethane acrylate resins, polyester acrylate resins, and polyethylene terephthalate resins, and olefin resins such as polypropylene can be used. The metals used to make up the tip can be those listed in the description of the wire.

[0132] If the indwelling device has a pusher and a connecting portion, it is preferable that the fiber layer is positioned distal to the distal end of the connecting portion, as shown in Figures 2 and 3.

[0133] As shown in Figure 2, the first retaining device 1 may have a first portion 151 in which the first coil 101 and the connecting portion 531 are arranged in overlapping positions. The first retaining device 1 may also have a second portion 161 in the longitudinal direction x from the distal end of the first coil 101 to the distal end of the first portion 151. Furthermore, as shown in Figure 3, the second retaining device 2 may have a first portion 152 in which the second coil 102 and the connecting portion 532 are arranged in overlapping positions. The second retaining device 2 may also have a second portion 162 in the longitudinal direction x from the distal end of the second coil 102 to the distal end of the first portion 152. Hereafter, when describing the configuration common to the first portion 151 and the first portion 152, and the second portion 161 and the second portion 162, these or each may simply be referred to as the first portion and the second portion.

[0134] As shown in Figures 9 to 11, in the first part, it is preferable that no fiber layer is arranged on the surface of the coil, and more preferably that no fiber layer is arranged on the outer surface of the coil. Furthermore, it is even more preferable that no fiber layer is arranged on the inner surface of the coil in the first part. If a fiber layer is present on the surface of the coil in the first part, the bonding strength between the coil and the connection may become unstable depending on the orientation of the fibers, but by not having a fiber layer on the surface of the coil in the first part, it becomes easier to stably fix the coil and the connection. However, as shown in Figures 2 and 3, a fiber layer may be present on the surface of the coil in the first part.

[0135] The position of the proximal end of the first section is the same as the position of the proximal end of the coil in the longitudinal direction x. The position of the distal end of the first section is the same as the position of the distal end of the connection in the longitudinal direction x. Here, the position of the proximal end of the coil refers to the most proximal position of the coil, including parts that are covered and not visible by components such as the tip and base tip. Similarly, the position of the distal end of the coil refers to the most distal position of the coil.

[0136] As shown in Figures 2 and 3, it is preferable that a fiber layer is arranged on the surface of the coil in the second part. Although not shown, it is preferable that the mass per unit length of the fiber layer in the second part is greater than the mass per unit length of the fiber layer in the first part.

[0137] The distal end of the second section is located at the same position as the distal end of the coil in the longitudinal direction x. The proximal end of the second section is located at the same position as the distal end of the first section.

[0138] The mass per unit length of the fiber layer in the first part and the mass per unit length of the fiber layer in the second part can be measured in the same manner as the mass per unit length of the fiber layer in the proximal or distal part of the coil.

[0139] In Figures 2 and 3, the second portion is longer than the first portion in the longitudinal direction x.

[0140] As shown in Figures 10 to 11, the fiber layer may be distributed throughout the entire second portion, or as shown in Figures 12 to 13, the fiber layer may be distributed only in a part of the second portion. For example, when the second portion is divided into a distal second portion and a proximal second portion in the longitudinal direction x, the fiber layer may be distributed only in the distal second portion or only in the proximal second portion.

[0141] Hereinafter, the fibers 40 of the fiber layer located in the first part may be referred to as the fibers 40 of the first part, and the fibers 40 of the fiber layer located in the second part may be referred to as the fibers 40 of the second part.

[0142] The fibers 40 of the first part and the fibers 40 of the second part may be of the same type or different types. For example, the fibers 40 of the first part and the fibers 40 of the second part may contain biodegradable polymer materials but not non-biodegradable polymer materials. The fibers 40 of the first part and the fibers 40 of the second part may contain non-biodegradable polymer materials but not biodegradable polymer materials. The fibers 40 of the first part may contain biodegradable polymer materials but not non-biodegradable polymer materials, and the fibers 40 of the second part may contain non-biodegradable polymer materials but not biodegradable polymer materials. The fibers 40 of the first part may contain non-degradable polymer materials but not biodegradable polymer materials, and the fibers 40 of the second part may contain biodegradable polymer materials but not non-biodegradable polymer materials.

[0143] When the biodegradable polymer material contained in the first and second parts of the fiber 40 is of the same type, it is preferable that the mass of the biodegradable polymer material per unit length of coil contained in the first part of the fiber 40 is greater than the mass of the biodegradable polymer material per unit length of coil contained in the second part of the fiber 40. This makes it easier for the decomposition rate of the first part to be relatively higher than that of the second part, thus allowing for different rates of drug release from the fiber layers in the first and second parts.

[0144] The non-biodegradable polymer material contained in the first and second parts of the fiber 40 may be of the same type. In that case, it is preferable that the mass per unit length of coil of the non-biodegradable polymer material contained in the first part of the fiber 40 is less than the mass per unit length of coil of the non-biodegradable polymer material contained in the second part of the fiber 40. By configuring the fiber 40 in this way, it becomes easier to make the decomposition rate of the first part of the fiber 40 relatively higher than that of the second part.

[0145] As shown in Figures 2 and 3, the fiber layer may be arranged along the entire length x of the coil. Since the flexibility of the coil tends to decrease when a fiber layer is provided, the fiber layer may be arranged only in a portion of the length x of the coil, as shown in Figures 9 to 15. For example, the fiber layer may be arranged in a section of 30% or more of the total length x of the coil, or in a section of 40% or more of the total length, or in a section of 50% or more of the total length. Alternatively, the fiber layer may be arranged in a section of 90% or less of the total length x of the coil, or in a section of 80% or less of the total length, or in a section of 70% or less of the total length.

[0146] The length of the fiber layer in the longitudinal direction x is preferably the same as or shorter than the length of the coil in the longitudinal direction x. The fiber layer is preferably not located distal to the distal end of the coil. Furthermore, the fiber layer is preferably not located proximal to the proximal end of the coil.

[0147] As shown in Figures 2 and 3, the entire length x of the coil is covered by the fiber layer, and the wire material does not need to be exposed.

[0148] As shown in Figures 2 to 3, the proximal end of the fiber layer may be positioned more proximal to the distal end of the proximal tip, but as shown in Figures 9 to 11, it is preferable that the proximal end of the fiber layer be positioned more distal to the distal end of the proximal tip. It is preferable that the distal end of the connecting portion be positioned more distal to the distal end of the proximal tip, but the distal end of the connecting portion may be positioned more proximal to the distal end of the proximal tip.

[0149] As shown in Figures 12 to 13, it is preferable that the fiber layer is not provided at the distal end of the coil. For example, if the wire at the distal end of the coil that is not covered by the tip is counted as the first turn from the distal end of the coil, it is preferable that the fiber layer is located proximal to the third turn of the coil from the distal end, more preferably proximal to the fifth turn of the coil from the distal end, and even more preferably proximal to the tenth turn of the coil from the distal end. By not providing a fiber layer at the distal end of the coil, the outer surface of the coil is more easily exposed at the distal end, which makes it easier for the coil to firmly engage with other parts of the coil and other coils when placing the coil in the knot, and makes it easier to form a framework.

[0150] As shown in Figures 12 to 13, it is preferable that the fiber layer is not provided at the distal end of the coil. For example, if the wire at the distal end of the coil that is not covered by the tip is counted as the first turn from the distal end of the coil, it is preferable that the fiber layer is located proximal to the third turn of the coil from the distal end, more preferably proximal to the fifth turn of the coil from the distal end, and even more preferably proximal to the tenth turn of the coil from the distal end. By not providing a fiber layer at the distal end of the coil, the outer surface of the coil is more easily exposed at the distal end, which makes it easier for the coil to firmly engage with other parts of the coil and other coils when placing the coil in the knot, and makes it easier to form a framework.

[0151] As shown in Figures 9 to 15, it is preferable that the fiber layer is not provided at the proximal end of the coil. For example, if the wire that is not covered by the base tip and is at the nearest end of the coil is counted as the first turn from the proximal side of the coil, it is preferable that the fiber layer is located distal to the third turn of the coil from the proximal side, more preferably distal to the fifth turn of the coil from the proximal side, and even more preferably distal to the tenth turn of the coil from the proximal side. By not providing a fiber layer at the proximal end of the coil, the outer surface of the coil is more easily exposed at the proximal end, which helps to prevent a decrease in the flexibility of the coil.

[0152] As shown in Figures 12 and 13, it is preferable that the fiber layer is arranged only in the portion of the coil excluding the distal and proximal ends.

[0153] Although not shown in the diagram, the distal end of the coil may not have a fiber layer, the proximal end of the coil may not have a fiber layer, and the fiber layer may be present only in the portion of the coil excluding the distal and proximal ends. This makes it easier to engage the distal end of the coil with other components while preventing a decrease in flexibility in the proximal end of the coil.

[0154] As shown in Figures 2 and 3, the distal end of the fiber layer may be positioned distal to the proximal end of the tip, but as shown in Figures 12 and 13, it is preferable that the distal end of the fiber layer be positioned proximal to the proximal end of the tip.

[0155] When the coil has a longitudinal direction x, it is preferable that the fiber layer is sandwiched between two adjacent wires in the longitudinal direction x, as shown in Figures 14 and 15. By sandwiching the fiber layer between the wires, the release of the drug 42 from the fiber layer becomes difficult in the sandwiched portion, thereby improving the sustained release of the drug.

[0156] In Figures 14 and 16, there is a gap 221 between adjacent wires 211 in the longitudinal direction x of the first coil 101. In Figures 15 and 17, there is a gap 222 between adjacent wires 212 in the longitudinal direction x of the second coil 102. When such gaps exist, some of the fibers of the fiber layer may be placed in the gaps. Here, a gap is defined as having a length in the longitudinal direction x that is at least 1 / 10 of the outer diameter of the wire.

[0157] Although not shown in the diagram, even if there are gaps between adjacent wires in the longitudinal direction x, a fiber layer does not necessarily have to be placed in the gaps.

[0158] Although not shown in the diagram, the fiber layer may be located radially y-outward from the innermost position of the outer surface 12 of the coil. That is, if the cross-sections of adjacent wires in the longitudinal direction x of the coil are circular, elliptical, etc., the fiber layer may be located in the recesses of the uneven structure provided on the surface of the coil.

[0159] As shown in Figures 2 and 3, the fiber layer may be arranged only radially y-outside of the outermost position on the outer surface of the coil.

[0160] As shown in Figures 14 to 17, the fiber layer may be positioned radially y-inward from the outermost position on the outer surface of the coil.

[0161] As shown in Figures 16 and 17, the fiber layer may be arranged on the inner circumferential surface of the coil. In this way, the fibers of the fiber layer may be located in the lumen of the coil. Since the fibers located in the lumen release the drug less easily than the fibers located on the outer surface, the sustained release of the drug can be improved.

[0162] As can be seen from Figures 16 and 17, if there is a gap between adjacent wires in the longitudinal direction x, the fiber layer may enter the lumen of the coil through the gap.

[0163] The coils shown in Figures 16 and 17 may be formed by providing a fiber layer on the outer surface of a wire, and then winding the wire with the fiber layer to form a coil shape.

[0164] System 1 can be appropriately combined with the first retaining device 1 and the second retaining device 2 described above. For example, System 1 may have at least one first retaining device 1 as shown in Figures 2, 10, 12, 14, and 16, and at least one second retaining device 2 as shown in Figures 3, 9, 11, 13, 15, and 17. Although not shown, System 1 may have one or more retaining devices in addition to the first retaining device 1 and the second retaining device 2. For the configuration of such retaining devices, refer to the description of the configuration of the first retaining device 1 and the second retaining device 2.

[0165] Although not shown in the diagram, the second agent may be impregnated into the interfiber gaps of the fiber layer. This allows the fiber layer to hold a large amount of the agent while preventing an initial burst of the agent. For details on the composition of the second agent, please refer to the description of agent 42.

[0166] Although not shown in the diagram, in addition to the fiber layer, a chemical agent may be placed on the surface of the coil. In this case, the chemical agent may be placed on the outer surface or on the inner surface. The chemical agent placed on the surface of the coil may be held on the surface of the coil as a chemical agent layer. A chemical agent layer may be placed on the outer surface of the coil, with the fiber layer placed outside the chemical agent layer in the radial direction y.

[0167] In addition to the fiber layer, the agents applied to the coil may be directly attached to the coil surface or indirectly attached to the coil surface via a bioadhesive. The type of bioadhesive material is not particularly limited, but for example, polysaccharide adhesives such as collagen, chitosan, and gelatin, polyethylene glycol-based hydrogel adhesives, and protein adhesives such as fibrin and collagen can be used.

[0168] If the drug is directly attached to the surface of the coil, it may be covered by a fiber layer to control the rate of drug release.

[0169] In addition to the fiber layer, the drug applied to the coil is preferably encapsulated. The drug encapsulated in the capsule may be directly attached to the surface of the coil, or it may be attached indirectly to the surface of the coil via a bioadhesive. The size of the capsule is preferably 10 nm or larger, more preferably 50 nm or larger, even more preferably 100 nm or larger, and preferably 500 nm or smaller, more preferably 400 nm or smaller, and even more preferably 200 nm or smaller. The capsule preferably contains a biodegradable material.

[0170] As shown in Figure 2, it is preferable that the first retaining device 1 has a first stretch resistance member 501 disposed in the lumen 111 of the first coil 101. As shown in Figure 3, it is preferable that the second retaining device 2 has a second stretch resistance member 502 disposed in the lumen 112 of the second coil 102. Hereinafter, the first stretch resistance member 51 and the second stretch resistance member 52 may be referred to individually or collectively as stretch resistance members. The stretch resistance members suppress the stretching of the coil in the longitudinal direction x during operation.

[0171] The stretch resistance member may be a long member made of a single wire or stranded wire. The stretch resistance member may be linear, corrugated, helical, or a combination thereof. One or more stretch resistance members may be arranged in the lumen. The stretch resistance member may be made of resin or metal. The stretch resistance member may be linear, corrugated, helical, or a combination thereof.

[0172] The first end of the stretch resistance member may be connected to the distal end of the coil (e.g., the distal end of the wire). The second end of the stretch resistance member may be connected to the proximal end of the coil (e.g., the proximal end of the wire) or to a connection point. The stretch resistance member may be positioned in the lumen in a folded state midway along its longitudinal axis.

[0173] Methods for connecting the stretch resistance member to other members include welding, crimping, adhesive bonding, engagement, linking, binding, ligation, and other physical fixing methods, or combinations thereof. Here, "connection" includes both forms in which two elements are directly connected and forms in which two elements are indirectly connected through one or more other elements. [Explanation of symbols]

[0174] 1: First Intra-vivo Device 2: Second Intra-biological Device 40: Fibers 41: Polymer materials 42: Medications 44: Core 45: Scabbard part 101: Coil 1 102: Second Coil 211: 1st wire rod 212:Second wire rod 251, 252: Tip 261, 262: Base tip 301: First fiber layer 302: Second fiber layer 501: First stretch resistance member 502: Second stretch resistance member 531, 532: Connection part 551, 552: Pusher x: Longitudinal direction of the coil y: radial direction of the coil z: Circumferential direction of the coil

Claims

1. A first retaining device having a first coil and a first fiber layer disposed on the outer surface of the first coil, The device comprises a second retaining device having a second coil and a second fiber layer disposed on the outer surface of the second coil, The first fiber layer and the second fiber layer each contain a polymer material and a fiber containing a drug, An implantation system for an in-vivo device in which the mass per unit length of the second fiber layer is less than the mass per unit length of the first fiber layer.

2. The implantation system for an in-vivo device according to claim 1, wherein the fiber includes a core-sheath type fiber having a core portion and a sheath portion, the core portion containing the drug, and the sheath portion containing the polymer material.

3. The implantation system for an in-vivo implantation device according to claim 1 or 2, wherein the mass per unit length of the first fiber layer disposed in the proximal part of the first coil is less than the mass per unit length of the first fiber layer disposed in the distal part of the first coil.

4. The implantation system for an in-vivo device according to claim 1 or 2, wherein the mass per unit length of the second fiber layer disposed in the proximal part of the second coil is less than the mass per unit length of the second fiber layer disposed in the distal part of the second coil.

5. The implantation system for an in-vivo device according to claim 1 or 2, wherein the mass per unit length of the second fiber layer disposed at the distal part of the second coil is less than the mass per unit length of the first fiber layer disposed at the proximal part of the first coil.

6. An in-vivo implantation system according to claim 1 or 2, wherein the second fiber layer is disposed only in the distal portion of the second coil, and the second fiber layer is not disposed in the proximal portion of the second coil.

7. The implantation system for an in-vivo device according to claim 1 or 2, wherein the polymer material is a biodegradable polymer material.

Images