Intra-biological implantable devices

Abstract

To provide an in-vivo implantable device that can suppress the unintended peripheral dispersal of blood clots. [Solution] An in-vivo implantation device 1 having a coil 10 and a hydrophilic coating layer 20 disposed on the outer peripheral surface 12 of the coil 10.

Description

Technical Field

[0001] The present invention relates to an implant for forming an embolism in blood vessels at a diseased part of blood vessels.

Background Art

[0002] Endovascular treatment is one of the treatment methods for vascular lesions such as aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal arteries, and abdominal aneurysms in the head and neck. In endovascular treatment, an embolization procedure is used to prevent, for example, the rupture of an aneurysm by placing an implant having an embolization coil at the target site and promoting thrombosis. In the embolization procedure, a technique of packing coils into the aneurysm is performed, and it has phases of Framing, Filling, and Finishing. In the embolization procedure, coils with different flexibility are generally selected for each phase. For example, in the Framing phase, it is necessary to create a framework shape within the aneurysm by making the coil crawl along the inner surface of the aneurysm. On the other hand, in the phases after Filling, a coil having more flexibility than that in Framing is selected to fill the coils into the framework formed in Framing. Several to several tens of coils are used in one embolization procedure. Patent Document 1 discloses an embolization device to be implanted in the body.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] As described in Patent Document 1, it has been known that the risk of aneurysm rupture can be reduced by the adhesion of thrombi to the surface of coils implanted in the body. However, excessive thrombus formation may affect non-lesion areas. For example, if it takes time to implant a coil, the coil may travel through the blood vessel with thrombi attached to its surface, which may cause unintended peripheral dispersal of thrombi. Therefore, the present invention aims to provide an in vivo implantable device that can suppress unintended peripheral dispersal of thrombi. [Means for solving the problem]

[0005] The in-vivo implantable device according to an embodiment of the present invention that can solve the above problems is as follows. [1] An in-vivo implant comprising a coil and a hydrophilic coating layer disposed on the outer surface of the coil.

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

[17] . [2] The in vivo implantation device according to [1], wherein when the length of the coil in the longitudinal direction is divided into three equal parts, a distal part, a central part, and a proximal part, the coating layer is located in at least one of the distal part and the proximal part, and the coating layer is not located in the central part. [3] The in-vivo implantation device according to [1], wherein the coating layer is distributed over the entire length of the coil. [4] The coil is constructed by winding a wire, The in-vivo implantation device further comprises a tip positioned at the distal end of the coil, The in-vivo device according to [1], wherein when the wire that is not covered by the tip of the coil and is at the farthest end is defined as the first turn of the coil, the coating layer is distributed only within the range of the first to tenth turns of the coil. [5] The in-vivo implantation device according to any one of [1] to [3], wherein the coil is constructed by winding wire, and when the coil is viewed from a direction perpendicular to the longitudinal axis, the coil has separation portions where the wires are separated from each other, and the coating layer is arranged distal to the separation portions in the longitudinal axis. [6] The in-vivo device according to any one of the items [1] to [5], wherein the thickness of the coating layer is 2 nm or more and 10 nm or less. [7] The in-vivo device according to any one of the following [1] to [6], wherein the water droplet contact angle on the outer surface of the coating layer is 10° or less. [8] The in-vivo device according to any one of the claims [1] to [7], wherein a drug layer is further disposed on the outer surface of the coil. [9] The in vivo implantation device according to [8], wherein the drug layer is located outside the coating layer in the radial direction of the coil.

[10] The in vivo implantation device according to [9], wherein when the length of the coil in the longitudinal direction is divided into three equal parts, a distal part, a central part, and a proximal part, the coating layer is positioned on the outermost side in the radial direction in the distal part and the proximal part, and the drug layer is positioned on the outermost side in the radial direction in the central part.

[11] The in vivo implantation device according to any one of the following items [8] to

[10] , wherein the coating layer and the drug layer are in contact, and the drug layer contains a lipid-soluble drug.

[12] The in-vivo device according to any one of the items [1] to

[11] , wherein the coating layer contains a drug.

[13] The in vivo implantation device according to any one of the following [1] to

[12] , wherein the coating layer comprises at least one of polyvinylpyrrolidone, polyethylene glycol, and heparin.

[14] The in-vivo device according to any one of the items [1] to

[11] , wherein the coating layer does not contain a drug.

[15] The in-vivo device according to any one of the claims [1] to

[14] , wherein the coating layer comprises an ionized compound.

[16] The in-vivo device according to any one of [1] to

[15] , wherein the coating layer comprises an osmotic pressure increasing agent.

[17] The in-vivo device according to any one of [1] to

[16] , further comprising a hydrophilic coating layer disposed on the inner surface of the coil. [Effects of the Invention]

[0007] With the above-mentioned in-vivo implantable device, even if the coil travels through the blood vessel during coil placement, the coating layer on the outer surface of the coil suppresses unintended peripheral dispersal of thrombi. Furthermore, the hydrophilic coating layer on the outer surface of the coil suppresses the delivery sliding load within the catheter used to transport the in-vivo implantable device, enabling smooth placement. In addition, the hydrophilic coating layer reduces friction between coils within the aneurysm, making it easier to pack the coils into the aneurysm. As a result, the coil density within the aneurysm increases, suppressing the occurrence of recanalization caused by blood entering the gaps between the coils. [Brief explanation of the drawing]

[0008] [Figure 1] This is a schematic diagram of an in-vivo implantable device according to an embodiment of the present invention. [Figure 2] Figure 1 shows a cross-sectional view (partially a side view) of the coil of the in-vivo implantation device along its longitudinal axis. [Figure 3] Figure 2 shows an enlarged cross-sectional view (partially a side view) of the area around the distal end of the coil of the in-vivo implantation device. [Figure 4] This is a schematic diagram illustrating a method for measuring the water droplet contact angle on the outer surface of a coating layer. [Figure 5] Figure 2 is a cross-sectional view (partially a side view) showing a modified example of the in-vivo implantation device. [Figure 6] Figure 3 is a cross-sectional view (partially a side view) showing a modified example of the in-vivo implantation device. [Figure 7] Figure 3 shows a cross-sectional view (partially a side view) illustrating another modified example of the in-vivo implantation device. [Figure 8] It is a cross-sectional view (partial side view) showing another modification example of the indwelling device in the living body shown in FIG. 2. [Figure 9] It is a cross-sectional view (partial side view) showing an enlarged view of the periphery of the distal end of the coil of the indwelling device in the living body shown in FIG. 8. [Figure 10] It is a cross-sectional view (partial side view) showing still another modification example of the indwelling device in the living body shown in FIG. 3. [Figure 11] It is a cross-sectional view (partial side view) showing still another modification example of the indwelling device in the living body shown in FIG. 3. [Figure 12] It is a cross-sectional view (partial side view) showing still another modification example of the indwelling device in the living body shown in FIG. 3. [Figure 13] It is a cross-sectional view (partial side view) showing still another modification example of the indwelling device in the living body shown in FIG. 3. [Figure 14] It is a cross-sectional view (partial side view) showing still another modification example of the indwelling device in the living body 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 a 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, reference numerals of members, 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] 1. Indwelling device in the living body An in-vivo implantation device according to an embodiment of the present invention comprises a coil and a hydrophilic coating layer disposed on the outer surface of the coil. Hereinafter, the in-vivo implantation device may be simply referred to as the implantation device. Examples of use of the implantation device include embolization to promote thrombosis at target sites such as cerebral aneurysms, head and neck aneurysms, arteriovenous malformations, arteriovenous fistulas, pulmonary vascular malformations, renal vascular malformations, renal artery aneurysms, and abdominal aneurysms. Among these, the implantation device is preferably an implantation device for cerebral aneurysms. Examples of aneurysm shapes include fusiform and saccular shapes.

[0011] Embolization has three phases: Framing, Filling, and Finishing. The implant can be used in one of these phases, or it can be used across two or three of these phases.

[0012] An in-vivo implantation device according to an embodiment of the present invention will be described with reference to Figures 1 to 14. Figure 1 is a schematic diagram of an in-vivo implantation device according to an embodiment of the present invention. Figure 2 is a cross-sectional view (partially a side view) along the longitudinal axis of the coil of the in-vivo implantation device shown in Figure 1. Figure 3 is an enlarged cross-sectional view (partially a side view) of the area around the distal end of the coil of the in-vivo implantation device shown in Figure 2. Figure 4 is a schematic diagram showing a method for measuring the water droplet contact angle on the outer surface of the coating layer. Figures 5 and 8 are cross-sectional views (partially a side view) showing other modified examples of the in-vivo implantation device shown in Figure 2. Figures 6, 7, and 10 to 14 are cross-sectional views (partially a side view) showing modified examples of the in-vivo implantation device shown in Figure 3. Figure 9 is an enlarged cross-sectional view (partially a side view) of the area around the distal end of the coil of the in-vivo implantation device shown in Figure 8. As shown in Figures 1 to 3, the implantation device 1 has a coil 10 and a hydrophilic coating layer 20 disposed on the outer circumferential surface 12 of the coil 10.

[0013] In this specification, unless otherwise specified, coil 10 refers to the configuration in the primary coil state. A primary coil that has been further shaped into a helical or three-dimensional shape is sometimes called a secondary coil. It is preferable that the coil 10 of the primary coil, as shown in Figure 2, is shaped to form the secondary coil shown in Figure 1. In Figure 1, the primary coil is wound to form a three-dimensional secondary coil shape. The coil 10 of the implantation device 1 is inserted into the lumen of the transport catheter in the form of a linear primary coil, as shown in Figure 2, and transported to the target site. When the primary coil is pushed out of the catheter, it is placed in the aneurysm in a state that has unfolded into a three-dimensional shape, as shown in Figure 1, or in a state that conforms to the shape of the aneurysm.

[0014] As can be seen from Figure 2, the coil 10 preferably has a longitudinal axis x, a radial direction y, and a circumferential direction z. The coil 10 preferably has a distal end and a proximal end in the longitudinal axis x. The proximal side of the coil 10 refers to the direction toward the user or operator's hand with respect to the longitudinal axis x of the coil 10, and the distal side refers to the opposite direction from the proximal side, i.e., the direction toward the treatment target. In Figure 2, the right side of the figure is the proximal side, and the left side of the figure is the distal side. The radial direction y of the coil 10 refers to the radial direction of the coil 10, and in the radial direction y, inward refers to the direction toward the longitudinal axis center of the coil 10, and outward refers to the direction extending radially from the longitudinal axis center on the opposite side from the inward direction. The circumferential direction z of the coil 10 refers to the direction around the longitudinal axis.

[0015] As shown in Figures 2 and 3, it is preferable that the coil 10 has an outer circumferential surface 12 and an inner circumferential surface 13. The surface of the coil 10 includes the outer circumferential surface 12 and the inner circumferential surface 13. It is preferable that the coil 10 has a lumen 11 extending in the longitudinal axis direction x. The outer circumferential surface 12 of the coil 10 faces the outside of the coil 10, i.e., the outside in the radial direction y, and the inner circumferential surface 13 of the coil 10 faces the lumen 11. It is preferable that a stretch resistance member 40, which will be described later, is placed in the lumen 11.

[0016] As shown in Figures 1 to 3, the coil 10 is preferably constructed by winding one or more wires 31 in a helical shape. Examples of wires 31 include single wires, stranded wires, and coiled wires, with single wires being preferred. Furthermore, it is preferable that the wire 31 is not a coiled wire.

[0017] The wire 31 is preferably biocompatible and flexible. Examples of materials that make up the wire 31 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 31 is made of a platinum-tungsten alloy.

[0018] The wire 31 has a longitudinal axis direction and has a distal end and a proximal end in the longitudinal axis direction. The wire 31 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 in the longitudinal axis direction. The shape of the cross section perpendicular to the longitudinal axis direction of the wire 31 may be circular, oval, polygonal, or a combination thereof. The shape of the cross section perpendicular to the longitudinal axis direction of the wire 31 may be the same throughout the entire longitudinal axis direction of the wire 31, or it may differ depending on the position in the longitudinal axis direction.

[0019] The outer diameter of the wire 31 is not particularly limited, but may be, for example, 25 μm or more, 30 μm or more, or 35 μm or more, and may be 75 μm or less, or 70 μm or less.

[0020] The outer diameter of the wire 31 may be the same in the longitudinal direction of the wire 31, or it may be different depending on the position in the longitudinal direction of the wire 31. If the cross-section of the wire 31 is not circular, the outer diameter of the wire 31 shall refer to the diameter equivalent to a circle.

[0021] The coil 10 may be a single-layer coil or a multi-layer coil having multiple layers. A portion of the coil 10 along its longitudinal axis x may be single-layered, while the remaining portion is multi-layered.

[0022] The density of the coil 10, i.e., the winding spacing, is not particularly limited and can be tightly wound, pitched, or a combination of these. The coil 10 may have adjacent wires 31 in contact with each other in the longitudinal axis x. The coil 10 may have adjacent wires 31 in contact with each other in only a part of the longitudinal axis x, or adjacent wires 31 in contact with each other along the entire longitudinal axis x. Furthermore, the coil 10 may not have adjacent wires 31 in contact with each other in the longitudinal axis x. Non-contact means that there is a gap between adjacent wires 31 in the longitudinal axis x of the coil 10.

[0023] The shape of the cross-section of the coil 10 perpendicular to the longitudinal axis x may be circular, oval, polygonal, or a combination thereof. The oval shape includes elliptical, egg-shaped, and rounded rectangular shapes. The same applies in the following description.

[0024] As shown in Figure 3, an uneven surface structure 32 may be provided on the surface of the coil 10 if the cross-sections of adjacent wires 31 in the longitudinal axis direction x of the coil 10 are circular, elliptical, etc.

[0025] The maximum and minimum outer diameters of coil 10 are not particularly limited and can be appropriately selected according to the phase of the procedure. For example, they may be 150 μm or more, 180 μm or more, or 200 μm or more, and may also be 400 μm or less, 380 μm or less, or 350 μm or less.

[0026] The outer diameter and / or inner diameter of the coil 10 may be the same size in the longitudinal axis x of the coil 10, or they may be different sizes depending on the position in the longitudinal axis x of the coil 10. If the cross-section of the coil 10 is not circular, the outer diameter of the coil 10 shall refer to the equivalent circular diameter. Similarly, if the inner lumen cross-section of the coil 10 is not circular, the inner diameter of the coil 10 shall refer to the equivalent circular diameter.

[0027] The coil 10 may have a constant outer diameter in the longitudinal axis direction x. A constant outer diameter means that the outer diameter of the coil 10 is substantially constant over the entire longitudinal axis direction x, and includes cases where the change in the outer diameter of the coil 10 over the entire longitudinal axis direction x is within ±5%.

[0028] As shown in Figures 2 and 3, a hydrophilic coating layer 20 is placed on the outer surface 12 of the coil 10. With the implantation device 1, even if the coil 10 travels through the blood vessel when it takes time to place the coil 10, the hydrophilic coating layer 20 on the outer surface 12 of the coil 10 can suppress unintended peripheral dispersal of thrombi. In addition, the hydrophilic coating layer 20 on the outer surface 12 of the coil 10 can suppress the delivery sliding load within the catheter used to transport the implantation device, enabling smooth placement. Furthermore, the presence of the hydrophilic coating layer 20 reduces friction between coils within the aneurysm, making it easier to pack the coil 10 into the aneurysm. As a result, the coil density within the aneurysm increases, suppressing the occurrence of recanalization caused by blood entering the gaps between the coils 10.

[0029] In order to achieve the aforementioned effect of suppressing peripheral scattering of thrombi, the coating layer 20 needs to be positioned on the outermost part of the coil 10 in the radial direction y, in at least a portion of the outer peripheral surface 12 of the coil 10. More specifically, the coating layer 20 needs to be positioned on the outermost part of the coil 10 in the radial direction y, in the portion of the implantation device 1 where the coil 10 is present.

[0030] The coating layer 20 may be applied only to a portion of the outer surface 12 of the coil 10. By partially applying the coating layer 20 in this way, the magnitude of the delivery sliding load within the catheter for transporting the implantation device and the magnitude of friction between coils within the aneurysm can be adjusted.

[0031] The coating layer 20 may be distributed over the entire outer surface 12 of the coil 10.

[0032] When the length x along the longitudinal axis of the coil 10 is divided into three equal parts, a distal portion 15, a central portion 16, and a proximal portion 17, the coating layer 20 may be arranged on the outer circumferential surface 12 of the distal portion 15 and / or the outer circumferential surface 12 of the proximal portion 17 of the coil 10.

[0033] When the length x along the longitudinal axis of the coil 10 is divided into three equal parts, a distal part 15, a central part 16, and a proximal part 17, the coating layer 20 does not necessarily have to be located in the central part 16 of the coil 10.

[0034] The coating layer 20 is arranged on a part and other part of the coil 10 in the longitudinal axis direction x, and the part and other part may be separated in the longitudinal axis direction x. The coating layer 20 is arranged on a part and other part of the coil 10 in the circumferential direction z, and the part and other part may be separated in the circumferential direction z.

[0035] Preferably, the coating layer 20 is in contact with the outer circumferential surface 12 of the coil 10. However, the coating layer 20 does not have to be in contact with the outer circumferential surface 12 of the coil 10. For example, the coating layer 20 may be arranged on the outer circumferential surface 12 of the coil 10 with another layer or component in between.

[0036] The coating layer 20 may have a single-layer structure or a multi-layer structure.

[0037] In this specification, a hydrophilic coating layer 20 is defined as one with a high affinity for water, specifically one in which the water droplet contact angle on the outer surface of the coating layer 20 is 90° or less. Here, the water droplet contact angle refers to the static contact angle. The droplet method can be used to measure the water droplet contact angle on the outer surface of the coating layer 20. The primary or secondary coil is unwound to obtain the wire. For example, in Figure 4, the primary coil, coil 10, is unwound to obtain the wire 31. The left-right direction of the paper in Figure 4 is parallel to the longitudinal axis direction of the wire 31. Next, 2.0 μl of pure water 100 is dropped onto the coating layer 20 on the surface of the wire 31, and the water droplet contact angle on the surface of the coating layer 20 after 1 minute is measured by the θ / 2 method. Specifically, using a Keyence VHX5000 digital microscope (or its alternative, the Keyence VHX-X1 digital microscope), the wire 31 and the water droplet are photographed from a direction perpendicular to the longitudinal axis of the wire 31 (perpendicular to the dripping direction). The water droplet contact angle, which is the angle between the coating layer 20 and the water droplet at five arbitrary locations on the coating layer 20, is measured, and the average value of these five locations is taken as the water droplet contact angle on the outer surface of the coating layer 20.

[0038] The water droplet contact angle of the outer surface of the coating layer 20 is preferably 60° or less, more preferably 30° or less, and even more preferably 10° or less. Furthermore, the water droplet contact angle of the outer surface of the coating layer 20 may be greater than 0°, 1° or more, or 5° or more.

[0039] The coating layer 20 preferably has hydrophilic groups. Examples of hydrophilic groups include hydroxyl groups, carboxyl groups, amino groups, amide groups, pyrrolidone groups, carbonyl groups, carboxymethyl groups, carboxylic acid anhydrides, ketone groups, sulfo groups, aldehyde groups, phosphoryl groups, thiol groups, and ammonium groups.

[0040] The coating layer 20 preferably contains a hydrophilic resin. Examples of hydrophilic resins included in the coating layer 20 include polyvinyl alcohol-based polymers such as polyvinyl alcohol (PVA), PVA crosslinked polymers, PVA water-absorbing gel freeze-thaw elastomers, and ethylene vinyl alcohol copolymers; synthetic polymers such as polylactic acid, polyhydroxyethyl methacrylate, polyacrylic acid, sodium polyacrylate, polyacrylamide, polyvinylpyrrolidone, polyvinyl methyl ether, polyethylene oxide, polyethylene glycol, polyglycolic acid, methyl vinyl ether maleic anhydride copolymer, polyhydroxyethyl phthalate, polydimethylolpropionic acid, methyl isopropyl ketone formaldehyde, polyethyleneimine, polystyrene sulfonate, and water-soluble nylon; and natural polymers such as carboxymethyl starch, dialdehyde starch, celluloses (CMC, MC, HEC, HPC), tannin, lignin, alginic acid, gum arabic, guar gum, tragacanth gum, gelatin, casein, glue, and collagen. The coating layer 20 may contain only one type of hydrophilic resin, or it may contain two or more types.

[0041] A coating layer 20 can be placed on the outer surface 12 of the coil 10 by immersing the coil 10 in a hydrophilic coating agent, applying a hydrophilic coating agent to the outer surface 12 of the coil 10, or covering the outer surface 12 of the coil 10 with a hydrophilic coating agent. Alternatively, a coating layer 20 can be placed on the outer surface 12 of the coil 10 by immersing the wire 31 constituting the coil 10 in a hydrophilic coating agent, applying a hydrophilic coating agent to the outer surface of the wire 31, or covering the outer surface of the wire 31 with a hydrophilic coating agent, and then winding the wire 31 to form the coil 10.

[0042] When the coating layer 20 is in contact with the surface of the coil 10, the coil 10 may have a roughened surface portion with a surface roughness Ra of 0.010 μm or more and 0.50 μm or less, and the coating layer 20 may be placed on the roughened surface portion, so that the coating layer 20 adheres well to the surface of the coil 10. Here, the surface roughness Ra of the coil 10 is the arithmetic mean roughness of the roughness curve in the circumferential direction z of the surface of the coil 10 between reference lengths, and the reference length is one-quarter of the circumference of the coil 10. By making the surface of the coil 10 rough in this way, the bonding strength between the roughened surface portion and the coating layer 20 is increased, and the peeling of the coating layer 20 from the coil 10 during the procedure can be prevented.

[0043] The arithmetic mean roughness Ra of coil 10 (primary coil) corresponds to the arithmetic mean roughness Ra specified in JIS B 0601 (2001) and is measured in accordance with JIS B 0633 (2001). For measurement, a measuring instrument specified in JIS B 0651 (2001) (for example, an ultra-precision non-contact three-dimensional measuring device, model: NH-3SP, manufactured by Mitaka Kohki Co., Ltd.) is used. For measurement, both ends of the wire 31 constituting coil 10 (primary coil), or the distal end of the wire 31 and a position several centimeters proximal to the distal end (for example, a position 5 centimeters proximal to the distal end) are grasped and pulled to straighten the wire 31. The surface roughness of the straightened wire 31 may then be measured in accordance with JIS B 0633 (2001). Similarly, if the coil 10 (primary coil) has been shaped to form a secondary coil, the wire 31 constituting the secondary coil may be straightened by gripping both ends of the wire 31, or the distal end of the wire 31 and a position several centimeters proximal to the distal end (for example, 5 centimeters proximal to the distal end), and pulling it to straighten the wire 31. The surface roughness of the straightened wire 31 may then be measured in accordance with JIS B 0633 (2001). The surface roughness Ra of the outer circumferential surface 12 of the coil 10 (primary coil) can be determined by measuring the surface roughness Ra of the portion of the straightened wire 31 that corresponds to the outer circumferential surface 12 of the coil 10 (primary coil). The surface roughness Ra of the inner circumferential surface 13 of the coil 10 (primary coil) can be determined by measuring the surface roughness Ra of the portion of the straightened wire 31 that corresponds to the inner circumferential surface 13 of the coil 10 (primary coil). Since the coil 10 is constructed by winding a wire 31, the outer circumference of the straightened wire 31, for example, in the range of 0° to 180°, corresponds to the outer surface 12 of the coil 10, and the outer circumference of the straightened wire 31, for example, in the range of 180° to 360°, corresponds to the inner surface 13 of the coil 10. Therefore, by measuring the surface roughness Ra of the wire 31, the surface roughness Ra of the coil 10 can be measured. When measuring the calculated average roughness Ra of a coil 10 (primary coil) that already has a coating layer 20, the coating layer 20 should be removed from the coil 10 before measurement. The method for removing the coating layer 20 is not limited, but for example, a method of dissolving it in an organic solvent such as ethanol, methanol, dichloromethane, or chloroform can be used.

[0044] The surface roughness Ra of the roughened portion of the coil 10 may be 0.015 μm or more, or 0.020 μm or more, and is preferably 0.30 μm or less, and more preferably 0.10 μm or less.

[0045] Of the surface of the coil 10, portions with a surface roughness Ra of less than 0.010 μm and portions with a surface roughness greater than 0.50 μm are not considered rough surfaces. Therefore, for example, when the primary coil 10 is constructed by tightly winding wires 31 with a circular or elliptical cross-section, the uneven structure formed between adjacent wires 31 of the coil 10 due to the circular or elliptical cross-section of the wires 31, and scratches larger than 0.50 μm that occur during the manufacturing process, are not considered rough surfaces.

[0046] The roughened portion may be distributed over the entire surface of the coil 10, but it is preferable that it be distributed over only a portion of the surface of the coil 10.

[0047] The coil 10 may have roughened surfaces on its outer circumferential surface 12 and inner circumferential surface 13. In that case, it is preferable that the surface roughness Ra of the roughened surface on the outer circumferential surface 12 is greater than the surface roughness Ra of the roughened surface on the inner circumferential surface 13, in order to facilitate adhesion of the coating layer 20 to the outer circumferential surface 12.

[0048] Preferably, the coating layer 20 does not contain any chemicals. This makes it easier for the coating layer 20 to be applied thinly to the surface of the coil 10, thereby preventing the coil 10 from hardening. In addition, it makes it easier to configure the coating layer 20 to adhere closely to the surface of the coil 10, thereby preventing the coating layer 20 from peeling off or cracking from the coil 10.

[0049] The coating layer 20 may contain a drug. The drug may be encapsulated within the coating layer 20. The drug may be dispersed within the coating layer 20. The drug may be an active ingredient (API) alone, or a mixture with other additives. Preferred additives include base materials, plasticizers, stabilizers, surfactants, etc. For information on the drug contained in the coating layer 20, refer to the description of the drug contained in the drug layer 60 described later. Note that when the coating layer 20 contains a drug, the embodiment in which the encapsulated drug is applied to the surface of the coil 10 is excluded.

[0050] The coating layer 20 preferably contains an ionized compound. Furthermore, the coating layer 20 preferably contains an osmotic pressure increasing agent. By including at least one of these in the coating layer 20, the hydrophilicity of the coating layer 20 is increased, thereby enhancing effects such as preventing unintended thrombus adhesion.

[0051] Examples of ionized compounds included in the coating layer 20 include heparin, polymethacrylic acid, calcium salts, polycarboxylic acids, and sodium citrate.

[0052] Examples of osmotic pressure increasing agents included in the coating layer 20 include urea; polyhydric alcohols such as glycerol; glycols such as polyethylene glycol and propylene glycol; and sugar alcohols such as sorbitol and mannitol.

[0053] The coating layer 20 preferably contains at least one of polyvinylpyrrolidone, polyethylene glycol, and heparin.

[0054] Within limits that do not impede the effects of the present invention, the coating layer 20 may contain various additives such as plasticizers, reaction regulators, pigments, flame retardants, antistatic agents, lubricants, adhesion enhancers, release modifiers, softeners, and surfactants.

[0055] The thickness of the coating layer 20 is preferably 2 nm or more and 10 nm or less. A thickness of 2 nm or more allows for a smooth coating surface, which enhances the effect of suppressing the delivery sliding load of the indwelling device 1 within the transport catheter and reducing friction between coils within the aneurysm. On the other hand, a thickness of 10 nm or less suppresses the increase in the outer diameter of the indwelling device 1, thereby improving ease of insertion into the aneurysm. The thickness of the coating layer 20 is more preferably 3 nm or more, and even more preferably 4 nm or more. Furthermore, the thickness of the coating layer 20 is more preferably 9 nm or less, and even more preferably 8 nm or less.

[0056] The thickness of the coating layer 20 may be uniform on the outer surface 12 of the coil 10, or it may vary in thickness from part to part. For example, the coating layer 20 may become thicker or thinner from the distal end to the proximal end of the coil 10.

[0057] The coating layer 20 may be arranged along the uneven surface structure 32 of the coil 10. In that case, it is preferable that the uneven surface structure 32 of the coil 10 is visible.

[0058] Because the coating layer 20 is placed on the outer peripheral surface 12 of the coil 10, the outer surface of the retaining device 1 may be flat in the portion of the coil 10 that has an uneven surface structure 32.

[0059] As shown in Figure 2, when the length of the coil 10 along its longitudinal axis is divided into three equal parts, a distal portion 15, a central portion 16, and a proximal portion 17, it is preferable that the coating layer 20 is located in at least one of the distal portion 15 and the proximal portion 17, and not in the central portion 16. The delivery sliding load tends to be higher in the distal portion 15 and the proximal portion 17, but by providing the coating layer 20 in this way, it is possible to reduce the sliding load in the distal portion 15 and the proximal portion 17 to about the same level as in the central portion 16, and the sliding load can be set to be approximately the same throughout the entire coil 10. As a result, when the sliding load suddenly increases during the procedure, the user is more likely to feel discomfort, and it becomes easier to detect procedural errors (for example, thrombus adhesion, damage to the coil 10, or peeling of the inner layer of the catheter used for transporting the indwelling device) at an early stage.

[0060] As shown in Figure 5, the coating layer 20 may be distributed over the entire length axis x of the coil 10. For example, the coating layer 20 may be distributed over the entire outer surface 12 of the coil 10. By distributing the coating layer 20 in this way, the delivery sliding load can be reduced over the entire coil 10.

[0061] As shown in Figures 1 to 3, the coil 10 is constructed by winding a wire 31, and the implantation device 1 may further have a tip 35 positioned at the distal end of the coil 10. The tip 35 covers a portion of the wire 31 to prevent the distal end of the wire 31 from directly contacting the inner wall surface of the body. The tip 35 may or may not be in contact with the stretch resistance member 40.

[0062] The shape of the tip 35 is not particularly limited, but may be, for example, hemispherical, semi-elongated, cylindrical, or polygonal prism.

[0063] The tip 35 may be joined to at least one of the outer circumferential surface 12 and the inner circumferential surface 13 of the coil 10. In addition, to prevent the tip 35 from falling off, a portion of the tip 35 may be placed in the lumen 11 at the distal end of the coil 10. The proximal end of the tip 35 may be located distal to the distal end of the wire 31, and vice versa.

[0064] The tip 35 may be made of a metal material or a resin. Examples of resins that make up the tip 35 include thermoplastic resins and UV-curing resins. Examples of resins that make up the tip 35 include ester resins such as epoxy acrylate resins, urethane acrylate resins, polyester acrylate resins, and polyethylene terephthalate resins, and olefin resins such as polypropylene. As the metal that makes up the tip 35, the metals listed in the description of the wire 31 can be used. The materials of the wire 31 and the tip 35 may be the same or different. The tip 35 may be made of the same material as the coating layer 20.

[0065] As shown in Figure 6, when the wire 31 that is not covered by the tip 35 and is at the furthest point of the coil 10 is considered to be the first turn n1 of the coil 10, the coating layer 20 is applied to the first turn n1 to the tenth turn n of the coil 10. 10 They may be placed only within the range up to n1. 10 Because the areas where the coating layer 20 is present tend to be hard, these hard areas can be used to locate gaps for positioning the coil 10 within the knot. Also, because the hardness changes at the boundary between the areas where the coating layer 20 is present and those where it is not, the coil 10 becomes easier to bend starting from this boundary. Therefore, the coating layer 20 is present from the first turn n1 to the tenth turn n 10By existing only within this range, an easily bendable portion of the coil 10 can be provided at the distal portion 15 of the coil 10, making it easier to extend the coil 10 in a spiral shape within the knot, starting from the easily bendable portion, when the coil 10 is placed inside the knot. Note that the wire 31 not covered by the tip 35 refers to the portion of the wire 31 whose outer surface 12 is located radially y outside the tip 35 when the coil 10 and the tip 35 are arranged to overlap in the longitudinal axis direction x.

[0066] The area where the coating layer 20 is applied is preferably at least n1 of the first turn of the coil 10, more preferably at least n2 of the second turn, and even more preferably at least n3 of the third turn. Furthermore, the area where the coating layer 20 is applied is preferably at least n of the tenth turn of the coil 10. 10 The following is preferable, and it may be 9th volume n9 or less, or 8th volume n8 or less.

[0067] As shown in Figure 7, the coil 10 is constructed by winding wire 31, and when viewed from a direction perpendicular to the longitudinal axis x, the coil 10 may have separation portions 18 where the wires 31 are separated from each other. In that case, the coating layer 20 may be positioned distal to the separation portion 18 in the longitudinal axis x. When the coil 10 has separation portions 18 and the coating layer 20 is positioned distal to the separation portion 18, the portion of the coil 10 distal to the separation portion 18 tends to become harder. Therefore, this hard portion can be used to find a gap for positioning the coil 10 within the knot. Also, because the hardness changes at the separation portion 18, the coil 10 becomes easier to bend starting from the separation portion 18. Therefore, when positioning the coil 10 within the knot, it becomes easier to extend the coil 10 in a spiral shape starting from the separation portion 18 within the knot. In other words, the separation portion 18 functions as an easily bendable portion that makes the coil 10 easier to bend.

[0068] A single coil 10 may have one or more separation portions 18, but it is preferable to have only one. This makes it easier to form a single starting point for bending the coil 10, thus making it easier to position the coil 10 within the knot.

[0069] The length of the separation portion 18 in the longitudinal axis direction x is preferably at least half the outer diameter of the wire 12, more preferably at least the outer diameter of the wire 12, and even more preferably at least 1.5 times the outer diameter of the wire 12. On the other hand, the length of the separation portion 18 in the longitudinal axis direction x is preferably no more than three times the outer diameter of the wire 12, and more preferably no more than 2.5 times the outer diameter of the wire 12. By setting the size of the separation portion 18 in this way, the coil 10 becomes easier to bend starting from the separation portion 18, and the coil 10 becomes easier to extend in a spiral shape within the knot.

[0070] The location where the separation portion 18 is provided is not particularly limited, but when the length x in the longitudinal axis direction of the coil 10 is divided into three equal parts, a distal portion 15, a central portion 16, and a proximal portion 17, it is preferable that the separation portion 18 is located in the distal portion 15, and more preferably at the distal end of the coil 10. When the wire 31 that is not covered by the tip 35 and is at the most distal end of the coil 10 is considered to be the first turn n1 of the coil 10, the separation portion 18 only needs to be located more proximal to the first turn n1, and may be located more proximal to the second turn n2 and more proximal to the third turn n3. Also, the tenth turn n 10 It may be positioned distal to the 9th volume n9.

[0071] The coating layer 20 may be positioned proximal to the separation portion 18 in the longitudinal axis x, but it is preferable that the coating layer 20 be positioned only distal to the separation portion 18 in the longitudinal axis x. In another embodiment, the coating layer 20 is positioned on the proximal portion 17 of the coil 10, and in the distal portion 16 of the coil 10, the coating layer 20 is positioned only distal to the separation portion 18, and the central portion 16 of the coil 10 does not need to have a coating layer 20.

[0072] As shown in Figures 8 and 9, it is preferable that a drug layer 60 is further arranged on the outer circumferential surface 12 of the coil 10. In the drug layer 60, the drug may be held on the surface of the coil 10 in the form of being enclosed in capsules such as microcapsules, or the drug enclosed in capsules may be held on the surface of the coil 10 in a layered manner.

[0073] The drug may be the active ingredient (API) alone, or a mixture with other additives. Preferred additives include base materials, plasticizers, stabilizers, surfactants, etc. In this specification, the amount of drug refers to the mass (mg) of the drug. If the drug is a mixture containing additives, the amount of drug refers to the mass (mg) of the mixture. Since the amount of drug is proportional to the thickness of the drug layer, the amount of drug can be determined from the thickness of the drug layer.

[0074] The types of drugs included in the drug layer 60 are not particularly limited, as long as they are necessary for the prevention or treatment of the affected area. The drugs may have at least one of the following effects: anti-inflammatory effect, antioxidant effect, antihypertensive effect, anticoagulant effect, and shear stress sensing 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, Furi). (e.g., radical scavengers), N-acetyl-L-cysteine ​​(NAC), calcium channel blockers (e.g., amlodipine, nifedipine, diltiazem), anti-alcohol drugs (e.g., disulfiram), antidepressants with shear stress inhibitory effects (e.g., paroxetine), diuretics (e.g., furosemide, trichlormethiazide, spironolactone), angiotensin-converting enzyme inhibitors (ACE inhibitors) (e.g., enalapril, lisinopril, perindopril) Examples include beta-blockers (such as metoprolol, atenolol, bisoprolol), alpha-blockers (such as prazosin, terazosin, doxazosin), alpha-beta-blockers (such as carvedilol, labetalol, butoxamine), anticoagulants (heparin, heparin derivatives, warfarin, antithrombin drugs such as dabigatran, rivaroxaban, etc.), and antiplatelet agents (such as aspirin, clopidogrel, ticagrelor, etc.).

[0075] The drug layer 60 preferably contains a lipid-soluble drug. The lipid-soluble drug can be any drug that dissolves in lipids, such as lipid-soluble statins, beta-blockers, dihydropyridine calcium channel blockers, anti-inflammatory drugs, and shear stress sensing inhibitors. Examples of lipid-soluble statins include atorvastatin, simvastatin, and rosuvastatin. Examples of lipid-soluble beta-blockers include metoprolol and propranolol. Examples of dihydropyridine calcium channel blockers include amlodipine and nifedipine. Examples of lipid-soluble anti-inflammatory drugs include the anti-alcohol drug disulfiram. Examples of lipid-soluble shear stress sensing inhibitors include antidepressants, specifically paroxetine, which is a P2X4 receptor inhibitor.

[0076] As shown in Figures 8 and 9, it is preferable that the drug is placed only on the surface of the coil 10 and that the lumen 11 of the coil 10 is not filled with the drug.

[0077] In the drug layer 60, the drug may be directly attached to the surface of the coil 10, or it may be indirectly attached to the surface of the coil 10 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.

[0078] In the drug layer 60, it is preferable that the drug is encapsulated in a capsule. This allows for effective release of the drug when the coil 10 is delivered to the affected area in the body. The encapsulated drug may be directly attached to the surface of the coil 10, or it may be attached indirectly to the surface of the coil 10 via a bioadhesive. Alternatively, the encapsulated drug may be held on the surface of the coil 10 in a layered manner.

[0079] The capsule size is preferably 10 nm or larger, more preferably 50 nm or larger, even more preferably 100 nm or larger, and also preferably 500 nm or smaller, more preferably 400 nm or smaller, and even more preferably 200 nm or smaller.

[0080] The drug is preferably encapsulated in a capsule containing 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. Among the biodegradable materials, PLGA is particularly preferred.

[0081] The capsule preferably has a structure in which multiple filamentous bioabsorbable polymers are condensed into a spherical shape. The number of filamentous bioabsorbable polymers is preferably 10,000 or more, more preferably 20,000 or more, and even more preferably 30,000 or more. The number of filamentous bioabsorbable polymers may also be 100,000 or less, 90,000 or less, or 80,000 or less. In particular, the capsule preferably has a structure in which 10,000 to 100,000 filamentous PLGAs are condensed into a spherical shape.

[0082] The glass transition temperature of the materials constituting the capsule is not particularly limited, but may be, for example, 40°C or higher, 41°C or higher, or 42°C or higher, and may also be 50°C or lower, 49°C or lower, or 48°C or lower.

[0083] The surface of the capsule is preferably covered with a coating material. The coating material can suppress the drug from leaching into the bloodstream or detaching during delivery of the implantation device 1 into the body. The material constituting the coating material is preferably a water-soluble polymer from the viewpoint of preventing initial bursting of the drug. Examples of coating material materials include carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxyethylcellulose, polyvinyl alcohol, alginic acid, pectin, gum arabic, gellan gum, guar gum, xanthan gum, carrageenan, and gelatin.

[0084] The surface of the capsule may be coated with a surfactant. The coating of a surfactant increases the fluidity of the capsule through the cell membrane, thereby improving the permeability of the drug through the cell membrane. The type of surfactant is not particularly limited, but a nonionic surfactant is preferred, such as polyoxyethylene sorbitan monolaurate, preferably Tween® 20, Tween® 80, etc.

[0085] As shown in Figures 8 and 9, it is preferable that the drug layer 60 is distributed only to a part of the outer circumferential surface 12. It is preferable that the drug layer 60 is not distributed over the entire outer circumferential surface 12. The drug layer 60 may also be distributed on the inner circumferential surface 13.

[0086] The drug layer 60 may have a single-layer structure or a multi-layer structure.

[0087] The drug layer 60 is arranged in a part and another part of the coil 10 in the longitudinal axis x direction, and the part and the other part may be separated in the longitudinal axis x direction.

[0088] As shown in Figures 8 and 9, when the length of the coil 10 along its longitudinal axis x is divided into three equal parts: a distal portion 15, a central portion 16, and a proximal portion 17, it is preferable that the coating layer 20 is positioned on the outermost side in the radial direction y in the distal portion 15 and the proximal portion 17, and the drug layer 60 is positioned on the outermost side in the radial direction y in the central portion 16. The presence of the coating layer 20 in the distal portion 15 makes the distal portion 15 more rigid, but this rigid portion can be used to locate the gap for positioning the coil 10 within the nodule. The presence of the coating layer 20 in the proximal portion 17 reduces the delivery sliding load, making it easier to insert the coil 10 into the nodule in the latter half of the procedure. In the central portion 16, the drug can be released from the drug layer 60 at an early stage of the procedure.

[0089] On the outer surface 12, the drug layer 60 does not necessarily have to be placed on the distal portion 15 and the proximal portion 17 of the coil 10. Alternatively, on the outer surface 12, the drug layer 60 may be placed radially y-inward from the coating layer 20 at the distal portion 15 and the proximal portion 17. This makes it easier to position the coating layer 20 as far outward as possible at the distal portion 15 and the proximal portion 17.

[0090] The central portion 16 may have a drug layer 60, but may not have a coating layer 20. Alternatively, in the central portion 16, the drug layer 60 may be located radially outward y from the coating layer 20.

[0091] The drug layer 60 may be positioned inside the coating layer 20 in the radial direction y of the coil 10, but as shown in Figure 10, the drug layer 60 may be positioned outside the coating layer 20 in the radial direction y of the coil 10. In this way, the drug layer 60 is held by the coating layer 20, which allows for adjustment of the release rate of the active ingredient of the drug from the drug layer 60.

[0092] When the drug layer 60 is located radially outward from the coating layer 20, it is preferable that the drug layer 60 is distributed only to a portion of the outer surface 12 of the coil 10, as shown in Figure 10. Furthermore, it is preferable that the drug layer 60 is not distributed over the entire coating layer 20. This allows the coating layer 20 to exert an effect of suppressing peripheral dispersal of thrombi.

[0093] As shown in Figure 10, it is preferable that the coating layer 20 and the drug layer 60 are in contact. In this case, it is preferable that the drug layer 60 contains a lipid-soluble drug. In the case of a lipid-soluble drug, it is thought that the drug is more likely to migrate into the endothelium when the affinity between the coating layer 20 as a base and the lipid-soluble drug is greater than the affinity between the coating layer 20 as a base and the endothelial layer of the blood vessel. As shown in Figure 10, by having the coating layer 20 in contact with the drug layer 60 containing the lipid-soluble drug, the influence of the affinity between the coating layer 20 and the lipid-soluble drug is increased, making it easier for the drug to migrate into the endothelium.

[0094] As shown in Figure 11, the indwelling device 1 may have a hydrophilic coating layer 20 disposed on the inner circumferential surface 13 of the coil 10. This makes it easier to retain the drug on the inner circumferential surface 13 side of the coil 10, thereby enhancing the drug sustained release effect.

[0095] The coating layer 20 may be applied to only a portion of the inner circumferential surface 13 of the coil 10, or it may be applied to the entire inner circumferential surface 13. The coating layer 20 may be applied to the entire outer circumferential surface 12 and the entire inner circumferential surface 13 of the coil 10.

[0096] For other configurations in which the coating layer 20 is arranged on the inner circumferential surface 13 of the coil 10, please refer to the description of the configuration in which the coating layer 20 is arranged on the outer circumferential surface 12 of the coil 10.

[0097] As shown in Figures 12 to 13, a hydrophilic coating layer 20 is not required on the inner circumferential surface 13 of the coil 10. In that case, it is preferable that a drug layer 60 is placed on the inner circumferential surface 13, and it is more preferable that the inner circumferential surface 13 and the drug layer 60 are in contact with each other.

[0098] Although not shown in the figures, the drug layer 60 may be distributed only to a portion of the inner surface 13 in the longitudinal axis x of the coil 10, or, as can be seen from Figure 12, it may be distributed over the entire inner surface 13.

[0099] Although not shown in the diagram, the drug layer 60 is located only on the inner circumferential surface 13 and does not necessarily have to be located on the outer circumferential surface 12. This makes it easier to prevent the initial bursting of the drug layer 60 when the coil 10 is inserted into the body.

[0100] As shown in Figure 13, it is preferable that the drug layer 60 is distributed only in a portion of the coating layer 20 on the outer peripheral surface 12 side. It is also preferable that the drug layer 60 is not distributed in the remaining area of ​​the coating layer 20 on the outer peripheral surface 12 side.

[0101] As shown in Figure 14, a hydrophilic coating layer 20 is provided on the inner circumferential surface 13 of the coil 10, and a drug layer 60 may be provided on a part and / or all of the area of ​​the coating layer 20 on the inner circumferential surface 13 of the coil 10.

[0102] The thickness of the drug layer 60 on the outer peripheral surface 12 may vary depending on the position in the longitudinal axis x, or it may be the same in the longitudinal axis x. The thickness of the drug layer 60 on the outer peripheral surface 12 may vary depending on the position in the circumferential direction z, or it may be the same in the circumferential direction z.

[0103] The thickness of the drug layer 60 on the inner circumferential surface 13 may vary depending on the position in the longitudinal axis x, or it may be the same in the longitudinal axis x. The thickness of the drug layer 60 on the inner circumferential surface 13 may vary depending on the position in the circumferential direction z, or it may be the same in the circumferential direction z.

[0104] The type of active pharmaceutical ingredient in the drug layer 60 on the outer surface 12 and the type of active pharmaceutical ingredient in the drug layer 60 on the inner surface 13 may be the same or different.

[0105] When the length x along the longitudinal axis of the coil 10 is divided into a distal section and a proximal section, the type of active pharmaceutical ingredient in the drug layer 60 located in the distal section of the coil 10 and the type of active pharmaceutical ingredient in the drug layer 60 located in the proximal section of the coil 10 may be the same or different.

[0106] As shown in Figure 2, it is preferable that the retaining device 1 has a stretch resistance member 40 positioned in the lumen 11 of the coil 10. The stretch resistance member 40 suppresses the stretching of the coil 10 in the longitudinal axis direction x during operation. The stretch resistance member 40 may be a long member made of a single wire or stranded wire. The stretch resistance member 40 has a longitudinal axis direction and has a first end and a second end in that longitudinal axis direction. The stretch resistance member 40 may be made of a single layer or multiple layers in the radial direction perpendicular to the longitudinal axis direction. The stretch resistance member 40 may have an inner layer made of stranded wire made of multiple wires and an outer layer provided outside the inner layer and containing a resin composition. Only one stretch resistance member 40 may be positioned in the lumen 11, or multiple members may be positioned.

[0107] The stretch resistance member 40 may be made of resin or metal. Examples of resins that make up the stretch resistance member 40 include polyester resins such as polyethylene terephthalate, polyamide resins such as nylon, and polyolefin resins such as polyethylene and polypropylene. Being made of resin increases flexibility and improves the delivery performance of the retaining device 1. Also, if the stretch resistance member 40 is made of resin, fracture due to metal fatigue during delivery can be eliminated. By making the length of the stretch resistance member 40 longer than the length of the coil 10, or by using a material that is easily stretched for the stretch resistance member 40, the tension caused by the end of the coil 10 stretching in a straight line due to insufficient length of the stretch resistance member 40 when the coil 10 is placed in the knot can be alleviated. Examples of metals that make up the stretch resistance member 40 include platinum, gold, rhodium, palladium, rhenium, silver, nickel, titanium, tantalum, tungsten and their alloys, and stainless steel.

[0108] The stretch resistance member 40 may be made of a different material than the wire 31 that makes up the coil 10. For example, the coil 10 may be made of a platinum-tungsten alloy, and the stretch resistance member 40 may be made of polypropylene resin.

[0109] The shape of the stretch resistance member 40 may be circular, oval, polygonal, or a combination thereof, with the cross-sectional shape perpendicular to its longitudinal axis.

[0110] To facilitate the placement of the stretch resistance member 40 in the lumen 11, the outer diameter of the stretch resistance member 40 is preferably less than half the inner diameter of the coil 10, and more preferably one-third or less. To prevent the stretch resistance member 40 from breaking, the outer diameter of the stretch resistance member 40 is preferably one-fifteenth or more the inner diameter of the coil 10, and more preferably one-tenth or more.

[0111] The stretch resistance member 40 can be linear, wave-shaped, helical, or a combination thereof.

[0112] The first end of the stretch resistance member 40 may be connected to the distal end of the coil 10, specifically to the distal end of the wire 31 that constitutes the coil 10. The second end of the stretch resistance member 40 may be connected to the proximal end of the coil 10, specifically to the proximal end of the wire 31. The second end of the stretch resistance member 40 may be connected to the connecting portion 50 (described later) that connects the coil 10 and the pusher 55. The stretch resistance member 40 may be placed in the lumen 11 in a state where it is folded back in the middle of its longitudinal axis. In that case, it is preferable that the folded portion 41 of the stretch resistance member 40 is connected to the distal or proximal end of the coil 10, and the first end and the second end are connected to the proximal or distal end of the coil 10, or to the distal end of the connecting portion 50. For example, in Figure 2, the stretch resistance member 40 has a folded portion 41 that is folded back in the middle of the longitudinal axis direction, the folded portion 41 is connected to the distal end of the coil 10, and the first end and the second end are connected to the connection portion 50.

[0113] Methods for connecting the stretch resistance member 40 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 the two elements are directly connected and forms in which the two elements are indirectly connected through one or more other elements.

[0114] It is preferable that the drug is placed on the surface of the stretch-resistant member 40. This makes it easier to efficiently deliver the drug necessary for treatment to the treatment site in the body. The drug may be placed only on a part of the stretch-resistant member 40 in the longitudinal direction, or it may be placed over the entire longitudinal direction of the stretch-resistant member 40. For a method of placing the drug on the stretch-resistant member 40, refer to the description of the method of providing the drug layer 60 on the coil 10.

[0115] As shown in Figures 1 to 3, the indwelling device 1 may further include a connecting portion 50 positioned in the lumen 11 of the coil 10 and connected to the proximal end of the coil 10, and a pusher 55 connected to the coil 10 via the connecting portion 50.

[0116] The retaining device 1 preferably has a release mechanism that allows the coil 10 to detach from the pusher 55. Examples of release mechanisms include hydraulic, electrical, and mechanical types, and among these, an electrical release mechanism is preferred. In the release mechanism, it is preferable that the connection portion 50 is heated and disconnected by electrical or thermal energy supplied through the pusher 55, thereby detaching the coil 10 from the pusher 55. In this case, it is preferable that the connection portion 50 is heated by a high-frequency current supplied between the distal end of the pusher 55 and the counter electrode plate.

[0117] The shape of the connecting portion 50 is not particularly limited and may be linear, rod-shaped, cylindrical, polygonal prism-shaped, cylindrical, polygonal tube-shaped, frustoconical, frustoconical, or a combination thereof.

[0118] The connecting portion 50 preferably contains a material that melts or dissolves upon heating. The connecting portion 50 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.

[0119] The pusher 55 is a rod-shaped or wire-shaped member used to hold the indwelling device 1 and push it distally. The pusher 55 can consist of one or more members. The pusher 55 may consist of a wire member, a coil member, or a combination thereof. The pusher 55 may be made of a conductive material such as stainless steel.

[0120] As shown in Figures 1 to 3, a base tip 36 may be provided at the proximal end of the coil 10 to close the proximal end of the coil 10. For details on the configuration of the base tip 36, please refer to the description of the tip tip 35. [Explanation of Symbols]

[0121] 1: Intra-vivo device 10: Coil 11:Lumen 12: Outer surface 13: Inner surface 15: Distal part 16: Central part 17: Proximal part 18: Separation part 20: Coating layer 31: Wire rod 35: Tip 36: Base tip 40: Stretch resistance member 50: Connection part 55: Pusher 60: Drug layer x: Longitudinal axis of the coil y: radial direction of the coil z: Circumferential direction of the coil

Claims

1. An in-vivo implant comprising a coil and a hydrophilic coating layer disposed on the outer surface of the coil.

2. The in-vivo implantation device according to claim 1, wherein when the length of the coil in the longitudinal direction is divided into three equal parts, a distal part, a central part, and a proximal part, the coating layer is disposed in at least one of the distal part and the proximal part, and the coating layer is not disposed in the central part.

3. The in-vivo implantation device according to claim 1, wherein the coating layer is distributed over the entire length of the coil in the longitudinal direction.

4. The aforementioned coil is constructed by winding a wire, The in-vivo implantation device further comprises a tip positioned at the distal end of the coil, The in-vivo implantation device according to claim 1 or 2, wherein when the wire that is not covered by the tip of the coil and is at the farthest end is defined as the first turn of the coil, the coating layer is distributed only within the range of the first to tenth turns of the coil.

5. The in-vivo implantation device according to claim 1 or 2, wherein the coil is constructed by winding wire, and when the coil is viewed from a direction perpendicular to the longitudinal axis, the coil has separation portions where the wires are separated from each other, and the coating layer is arranged distal to the separation portions in the longitudinal axis direction.

6. The in-vivo device according to claim 1 or 2, wherein the thickness of the coating layer is 2 nm or more and 10 nm or less.

7. The in-vivo device according to claim 1 or 2, wherein the water droplet contact angle on the outer surface of the coating layer is 10° or less.

8. The in-vivo device according to claim 1 or 2, wherein a drug layer is further disposed on the outer surface of the coil.

9. The in-vivo device according to claim 8, wherein the drug layer is positioned outside the coating layer in the radial direction of the coil.

10. The in-vivo device according to claim 9, wherein when the length of the coil in the longitudinal direction is divided into three equal parts, a distal portion, a central portion, and a proximal portion, the coating layer is positioned on the outermost side in the radial direction in the distal portion and the proximal portion, and the drug layer is positioned on the outermost side in the radial direction in the central portion.

11. The in vivo implantation device according to claim 9, wherein the coating layer and the drug layer are in contact, and the drug layer contains a lipid-soluble drug.

12. The in-vivo device according to claim 1 or 2, wherein the coating layer contains a drug.

13. The in-vivo device according to claim 1 or 2, wherein the coating layer comprises at least one of polyvinylpyrrolidone, polyethylene glycol, and heparin.

14. The in-vivo device according to claim 1 or 2, wherein the coating layer does not contain any drugs.

15. The in-vivo device according to claim 1 or 2, wherein the coating layer comprises an ionized compound.

16. The in-vivo device according to claim 1 or 2, wherein the coating layer comprises an osmotic pressure increasing agent.

17. The in-vivo device according to claim 1 or 2, further comprising a hydrophilic coating layer disposed on the inner circumferential surface of the coil.

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