In-vivo indwelling tool

Abstract

An in-vivo indwelling tool (1) has a tubular body (10) having a longitudinal direction (x), and a fiber layer (30) disposed on an outer peripheral surface (12) of the tubular body (10). The fiber layer (30) contains fibers containing a polymer material and a drug. The degree of orientation of the fibers of the fiber layer (30) measured by a predetermined method is 60% or more.

Description

Intravascular implant

[0001] The present disclosure relates to an intravascular implant having a tubular body implanted in the body.

[0002] In minimally invasive interventional treatments for lesions or abnormalities such as aneurysms, thrombi, stenoses, and occlusions in blood vessels and the digestive tract, a tubular body implanted in the body is used. Examples of such tubular bodies include coils for embolization, stents, stent grafts, injection catheters, prosthetic valves, and the like. For example, in endovascular treatment, an embolization coil-containing intravascular implant is placed at the target site to promote thrombosis, and embolization is used to prevent, for example, the rupture of an aneurysm. There is also a treatment method in which a stent is inserted into a stenosed or occluded blood vessel to expand the blood vessel and ensure blood flow. Examples include coronary stent implantation for treating coronary artery stenosis or occlusion, and carotid artery stent implantation for improving cerebral artery stenosis. Patent Documents 1 to 3 disclose intravascular implants in which a coil holds a drug.

[0003] US Patent Application Publication No. 2007 / 299461, Japanese Patent Publication No. 2013-537046, Japanese Unexamined Patent Application Publication No. 2015-195978

[0004] However, the intravascular implants described in Patent Documents 1 to 3 had room for improvement in terms of the drug release efficiency. Therefore, an object to be solved by the present disclosure is to provide an intravascular implant capable of efficiently releasing a drug in the body.

[0005] An in-vivo implantation device according to an embodiment of the present disclosure that can solve the above problems is as follows: [1] An in-vivo implantation device comprising: a tubular body having a longitudinal direction; and a fiber layer disposed on the outer surface of the tubular body, wherein the fiber layer contains fibers comprising a polymer material and a drug, and the degree of orientation of the fibers in the fiber layer, measured by the following method, is 60% or more. (Method) An image of the tubular body viewed from the side is acquired, and for each of the 20 target fibers selected in the image, the relative angle θ (0° < θ ≤ 180°) of the direction of extension of the target fiber with respect to the direction parallel to the longitudinal direction is measured. The relative angle θ is classified into 10 classes obtained by equally dividing the range greater than 0° and less than or equal to 180°, and the frequency distribution for each class is obtained. The quantity ratio (%) of the sum of the frequencies of two adjacent classes to the total frequency is the degree of orientation of the fibers. Here, the first and tenth classes are considered to be adjacent.

[0006] Furthermore, the in-vivo implantation device according to the embodiment is preferably any of the following [2] to [8]. [2] The in-vivo implantation device according to [1], wherein the fiber includes a core-sheath type fiber having a core and a sheath, the core contains the drug and the sheath contains the polymer material. [3] The in-vivo implantation device according to [1] or [2], wherein the degree of orientation of the fibers in the fiber layer is 80% or more. [4] The in-vivo implantation device according to any one of [1] to [3], wherein the average fiber length of the fiber is 100 mm or more, and the fiber in the fiber layer is wound around the outer surface of the tubular body. [5] The in-vivo implantation device according to any one of [1] to [4], wherein the tubular body is a coil formed by winding a long wire. [6] The in-vivo implantation device according to [5], wherein the fiber is oriented in the longitudinal axis direction of the wire. [7] The in-vivo implantation device according to [5], wherein the fiber is oriented in a direction perpendicular to the longitudinal axis direction of the wire. [8] The in-vivo implantation device according to any one of the items [1] to [7], wherein the polymer material is a biodegradable polymer material.

[0007] In the above-mentioned in-vivo implantation device, the fibrous layer contains the drug, which suppresses the occurrence of an initial burst of the drug compared to a configuration where the drug is directly applied to the surface of the tubular body. In addition, because the fibers in the fibrous layer are oriented in a specific direction, it becomes easier to make the release rate of the drug contained in the fibers uniform over a wide area of ​​the fibrous layer.

[0008] These are schematic diagrams of an in-vivo implantation device according to an embodiment of the present disclosure. This is a side view (partially a cross-sectional view) of the tubular body of the in-vivo implantation device shown in Figure 1, along the longitudinal direction, showing the tubular body extended in a straight line. This is a cross-sectional view (partially a side view) of the tubular body of the in-vivo implantation device shown in Figure 1, along the longitudinal direction, showing the tubular body extended in a straight line. These are cross-sectional views showing the fiber layer of the in-vivo implantation device shown in Figures 2 and 3. This is a cut end view showing a modified example of the in-vivo implantation device shown in Figure 3. This is a schematic diagram showing the fiber structure of the fiber layer of the in-vivo implantation device according to an embodiment of the present disclosure. This is a schematic diagram showing a modified example of the fiber structure shown in Figure 6. This is a schematic diagram showing a method for measuring the degree of orientation. This is a schematic diagram showing the start and end points of a fiber when the fiber has a branching portion. This is a schematic diagram showing a modified example of the fiber orientation shown in Figure 8. This is a schematic diagram showing another modified example of the fiber orientation shown in Figure 8. This is a side view (partially a cross-sectional view) showing a modified example of the in-vivo implantation device shown in Figure 2. This is a side view (partially a cross-sectional view) showing another modified example of the in-vivo implant shown in Figure 2. This is a side view (partially a cross-sectional view) showing yet another modified example of the in-vivo implant shown in Figure 2. This is a side view (partially a cross-sectional view) showing yet another modified example of the in-vivo implant shown in Figure 2. This is a side view (partially a cross-sectional view) showing yet another modified example of the in-vivo implant shown in Figure 2. This is a side view (partially a cross-sectional view) showing yet another modified example of the in-vivo implant shown in Figure 2. This is a cross-sectional view showing another modified example of the in-vivo implant shown in Figure 3. This is a side view (partially a cross-sectional view) showing yet another modified example of the in-vivo implant shown in Figure 2.

[0009] The contents of this disclosure will be described in more detail below based on the embodiments described below. However, the contents of this disclosure are not limited by the embodiments described below, and it is certainly possible to implement the disclosure with appropriate modifications within the scope that is consistent with the spirit of the preceding and following descriptions, and all such modifications are included within the technical scope of this disclosure. In addition, hatching and component reference numerals may be omitted in the drawings for convenience, in which case refer to the specification or other drawings. Furthermore, the dimensions of various components in the drawings may differ from the actual dimensions, as priority is given to helping to understand the features of this disclosure.

[0010] The in-vivo implantation device according to the embodiments of this disclosure comprises a tubular body having a longitudinal direction and a fibrous layer arranged on the outer surface of the tubular body, wherein the fibrous layer contains fibers comprising a polymer material and a drug, and the degree of orientation of the fibers in the fibrous layer, as measured by a predetermined method, is 60% or more. Hereinafter, the in-vivo implantation device may be simply referred to as the implantation device. The implantation device is implanted in the body in minimally invasive treatment of lesions or abnormalities such as aneurysms, thrombi, stenosis, and occlusion in blood vessels and gastrointestinal tracts. The implantation device is preferably an implantation device for cerebral aneurysms. The implantation device for cerebral aneurysms can be used in any one of the Framing, Filling, and Finishing phases, or it can be used over any two or three phases.

[0011] An in-vivo implantation device according to an embodiment of the present disclosure will be described with reference to Figures 1 to 19. Figure 1 is a schematic diagram of an in-vivo implantation device according to an embodiment of the present disclosure. Figure 2 is a side view (partially a cross-sectional view) along the longitudinal direction of the tubular body of the in-vivo implantation device shown in Figure 1, showing the tubular body extended in a straight line. Figure 3 is a cross-sectional view (partially a side view) along the longitudinal direction of the tubular body of the in-vivo implantation device shown in Figure 1, showing the tubular body extended in a straight line. Figure 4 is a cross-sectional view showing the fiber layer of the in-vivo implantation device shown in Figures 2 to 3. Figure 5 is a cut end view showing a modified example of the in-vivo implantation device shown in Figure 3. Figure 6 is a schematic diagram showing the fiber structure of the fiber layer of the in-vivo implantation device according to an embodiment of the present disclosure. Figure 7 is a schematic diagram showing a modified example of the fiber structure shown in Figure 6. Figure 8 is a schematic diagram showing a method for measuring the degree of orientation. Figure 9 is a schematic diagram showing the start and end points of a fiber when the fiber has a branching portion. Figures 10 to 11 are schematic diagrams showing modified fiber orientations as shown in Figure 8. Figures 12 to 17 and 19 are side views (partially cross-sectional views) showing yet another modified in-vivo device as shown in Figure 2. Figure 18 is a cross-sectional view showing yet another modified in-vivo device as shown in Figure 3. In Figure 1, the fiber layer 30 is omitted to facilitate understanding of the shape of the secondary coil. As shown in Figures 2, 3 and 5, the in-vivo device 1 has a tubular body 10 and a fiber layer 30.

[0012] As can be seen from Figures 2, 3, and 5, the tubular body 10 has a longitudinal direction x, and preferably has a radial direction y and a circumferential direction z. The tubular body 10 preferably has a distal end and a proximal end in the longitudinal direction x. The proximal side of the tubular body 10 refers to the direction toward the user or operator's hand with respect to the longitudinal direction x of the tubular body 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, 3, and 5, 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 tubular body 10 refers to the radial direction of the tubular body 10, and in the radial direction y, inward refers to the direction toward the longitudinal axis center of the tubular body 10, and outward refers to the direction extending radially from the longitudinal axis center on the opposite side from inward. The circumferential direction z of the tubular body 10 refers to the direction around the longitudinal axis. In the following, when the length of each member of the tubular body 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.

[0013] As shown in Figure 3, the tubular body 10 has a lumen 11. Preferably, the lumen 11 extends in the longitudinal direction x. Preferably, the tubular body 10 has an outer circumferential surface 12 and an inner circumferential surface 13. The outer circumferential surface 12 faces the outside of the tubular body 10 in the radial direction y, and the inner circumferential surface 13 faces the lumen 11. The tubular body 10 may have multiple lumen 11s, but it is preferable that it has only one lumen 11.

[0014] The tubular body 10 is used, for example, to treat various diseases caused by narrowing or occlusion of tubular structures in the body, such as the digestive tract or blood vessels, or to block abnormal dilated areas of blood vessels, such as aneurysms. The tubular body 10 may be placed in the lesion to expand the lesion, such as a narrowed or occluded area, from the inside and maintain the diameter of the lumen, or it may be used to entangle and remove thrombi or the like that formed in or around the lesion, thereby restoring the diameter of the lumen in that lesion.

[0015] The tubular body 10 is preferably made of resin, metal, or a combination of resin and metal. Examples of the tubular body 10 include resin tubes, metal tubes, hollow bodies formed by arranging wires in a predetermined pattern, hollow bodies coated with resin on at least one of their inner or outer surfaces, or combinations thereof, for example, those connected in the longitudinal direction x. Resin tubes can be manufactured, for example, by extrusion molding. Examples of hollow bodies with wires arranged in a predetermined pattern include cylindrical bodies having a mesh structure by simply crossing or weaving wires, and coils in which wires are wound. The wires may be one or more single wires, or one or more stranded wires. The type of mesh structure is not particularly limited, nor are the number of turns or density of the coils. The mesh structure or coil may be formed at a constant density over the entire longitudinal direction x of the tubular body 10, or the density may differ depending on the position in the longitudinal direction x of the tubular body 10. To increase the flexibility of the metal tube, notches or grooves may be formed on the outer surface of the metal tube. The shape of the cuts and grooves can be straight, arcuate, annular, spiral, or a combination of these.

[0016] As the tubular body 10, a coil, stent, stent graft, injection catheter, prosthesis valve, etc. can be used as an occlusion device.

[0017] The constituent material of the tubular body 10 only needs to be biocompatible. Examples of resins constituting the tubular body 10 include polyamide resins, polyester resins, polyurethane resins, polyolefin resins, fluororesins, vinyl chloride resins, silicone resins, natural rubber, synthetic rubber, etc. These may be used individually or in combination of two or more. The resin constituting the tubular body 10 may be either a thermoplastic resin or a thermosetting resin, but a thermoplastic resin is preferred. Examples of metals constituting the tubular body 10 include stainless steel such as SUS304 and SUS316, platinum, gold, titanium, nickel, cobalt, chromium, tungsten, Ni-Ti alloy, Co-Cr alloy, Pt-W alloy, or combinations thereof. The tubular body 10 may have a laminated structure made of different materials or the same material.

[0018] As shown in Figure 5, the tubular body 10 is preferably a stent 16. The stent 16 is an expandable structure composed of a mesh structure, such as a mesh, and includes a plurality of support columns. The stent 16 can be formed from a pattern of interconnected structural elements that expand and contract in the circumferential and axial directions, for example. Examples of stents include a coil-shaped type made of a single linear metal or polymer material, a type made by cutting out a metal tube or polymer tube with a laser, a type assembled by welding linear parts, and a type made by weaving multiple linear metals.

[0019] The stent 16 may be a balloon-expandable stent, but it is preferable that it be a self-expanding stent. This allows the stent 16 to expand to a predetermined size by removing the external members that suppress its expansion.

[0020] As shown in Figures 2 and 3, the tubular body 10 is preferably a coil 15 formed by winding a long wire. By inserting the coil 15 into the blood vessels of the affected area, blood flow can be blocked and the inflow of blood to the abnormal site can be suppressed, thereby reducing the risk of disease progression and rupture.

[0021] In this specification, unless otherwise specified, coil 15 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 15 of the primary coil, as shown in Figures 2 to 3, 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 15 is inserted into the lumen of the transport catheter in the form of a linear primary coil, as shown in Figures 2 to 3, and transported to the target site. When the primary coil is pushed out of the catheter, it is left 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.

[0022] As shown in Figures 2 and 3, the coil 15 is preferably constructed by winding a wire 21, and more preferably by winding one or more wires 21 in a helical shape. Examples of the wire 21 include a single wire, a stranded wire, and a coiled wire, with a single wire being preferred. Furthermore, it is preferable that the wire 21 is not a coiled wire.

[0023] As shown in Figures 10 to 11, the wire 21 has a longitudinal axis direction p, and has a distal end and a proximal end in the longitudinal axis direction p. The wire 21 may be composed of a single wire from the distal end to the proximal end, or it may be composed of multiple wires connected to each other in the longitudinal axis direction p. The shape of the cross section perpendicular to the longitudinal axis direction p of the wire 21 may be circular, oval, polygonal, or a combination thereof. The shape of the cross section perpendicular to the longitudinal axis direction p of the wire 21 may be the same throughout the entire longitudinal axis direction p of the wire 21, or it may differ depending on the position in the longitudinal axis direction p.

[0024] The outer diameter of the wire 21 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.

[0025] The outer diameter of the wire 21 may be the same in the longitudinal axis direction p of the wire 21, or it may be different depending on the position in the longitudinal axis direction p of the wire 21. If the cross-section of the wire 21 is not circular, the outer diameter of the wire 21 shall refer to the diameter equivalent to a circle.

[0026] The coil 15 may be a single-layer coil or a multi-layer coil having multiple layers. A portion of the coil 15 in the longitudinal direction x may be a single layer, and the remaining portion may be multi-layer.

[0027] The density of the coil 15, i.e., the winding spacing, is not particularly limited and can be tightly wound, pitched, or a combination of these. The coil 15 may have adjacent wires 21 in contact with each other in the longitudinal direction x. The coil 15 may have adjacent wires 21 in contact with each other in only a part of the longitudinal direction x, or adjacent wires 21 in contact with each other throughout the entire longitudinal direction x. Furthermore, the coil 15 may not have adjacent wires 21 in contact with each other in the longitudinal direction x. The state of not being in contact means that there is a gap between adjacent wires 21 in the longitudinal direction x of the coil 15.

[0028] The outer edge shape of the cross-section perpendicular to the longitudinal direction x of the coil 15 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.

[0029] The surface of the coil 15 may have an uneven surface structure if the cross-sections of adjacent wires 21 in the longitudinal direction x of the coil 15 are circular, elliptical, or the like.

[0030] The maximum and minimum outer diameters of the coil 15 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.

[0031] The outer diameter and / or inner diameter of the coil 15 may be the same size in the longitudinal direction x of the coil 15, or they may be different sizes depending on the position in the longitudinal direction x of the coil 15. If the cross-section of the coil 15 is not circular, the outer diameter of the coil 15 shall refer to the equivalent diameter of a circle. Similarly, if the inner lumen cross-section of the coil 15 is not circular, the inner diameter of the coil 15 shall refer to the equivalent diameter of a circle.

[0032] The coil 15 may have a constant outer diameter in the longitudinal direction x. A constant outer diameter means that the outer diameter of the coil 15 is substantially constant over the entire longitudinal direction x, and includes cases where the change in the outer diameter of the coil 15 over the entire longitudinal direction x is within ±5%.

[0033] The retaining device 1 has a fiber layer 30 arranged on the outer surface 12 of the tubular body 10. The fiber layer 30 only needs to have at least some of its fibers 40 arranged on the outer surface 12.

[0034] The fiber layer 30 may be arranged only on a part of the outer surface 12 of the tubular body 10, or it may be arranged on the entire outer surface 12 of the tubular body 10.

[0035] As the fiber layer 30, 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 nonwoven fabric or a 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 30, the fibers 40 may be joined to each other by entanglement, or they may be joined by heat fusion.

[0036] As shown in Figures 2-3 and 5, it is preferable that the fiber layer 30 has a cylindrical shape arranged along the peripheral wall of the tubular body 10. As shown in Figure 4, it is preferable that the fiber layer 30 has a cylindrical shape with only one lumen 31. As can be seen from Figures 2-3 and 5, it is preferable that the axis center in the longitudinal direction x of the tubular body 10 and the axis center in the longitudinal direction of the cylindrical fiber layer 30 coincide.

[0037] If the fiber layer 30 has a cylindrical shape, it is preferable that the fiber layer 30 has an outer peripheral surface 32 facing outwards from the retaining device 1 and an inner peripheral surface 33 facing outwards from the outer peripheral surface 12 of the tubular body 10.

[0038] As can be seen from Figures 2-3 and 5, it is preferable that the inner circumferential surface 33 of the fiber layer 30 is in contact with the outer circumferential surface 12 of the tubular body 10. It is preferable that no other members are disposed between the tubular body 10 and the fiber layer 30 in the radial direction y. For example, it is preferable that no drug is applied to the outer circumferential surface 12 of the tubular body 10 in any form other than the fiber layer 30.

[0039] The fiber layer 30 may consist of a single layer or multiple layers.

[0040] The fiber layer 30 may be fixed to the tubular body 10. The method of fixation is not particularly limited and can include suturing, bonding, welding, clamping, etc. The fiber layer 30 may be fixed to the tubular body 10 by a part of the fiber layer 30 being sandwiched between two wires 21 that constitute the tubular body 10. The fiber layer 30 may be fixed by bonding or welding its inner circumferential surface 33 to the outer circumferential surface 12 of the tubular body 10.

[0041] In the fiber layer 30, the fibers 40 may be wound around the outer surface 12 of the tubular body 10. That is, in the fiber layer 30, the fibers 40 may be wound around the axis in the longitudinal direction x of the tubular body 10.

[0042] The tubular body 10 may have only one fiber layer 30, or it may have multiple fiber layers 30. A first fiber layer 30 may be located at the distal end of the tubular body 10, and a second fiber layer 30 may be located at the proximal end of the tubular body 10. It is preferable that the multiple fiber layers 30 are arranged in the longitudinal direction x. The multiple fiber layers 30 may be spaced apart from each other in the longitudinal direction x, or they may be in contact with each other. It is preferable that all of the multiple fiber layers 30 have a cylindrical shape.

[0043] The fiber layer 30 includes fibers 40. Generally, a fiber is a thin, thread-like substance. In this specification, the fiber 40 refers to those with an average fiber diameter of 100 μm or less, excluding those with an average fiber diameter exceeding 100 μm. The average fiber diameter of the fiber 40 can be measured by the following method. Using a scanning electron microscope or a laser microscope (for example, the scanning transmission electron microscope (STEM-EDX / EELS) HD-2700 manufactured by Hitachi High-Technologies Corporation), an image of the fiber at a magnification of 1000 times is obtained. For the method of acquiring the image, reference can be made to the description of the acquisition of the image 60 described later. In the obtained image, the arithmetic mean value of the diameters of at least 20 fibers is taken as the average fiber diameter of the fiber 40. When measuring the diameter of the fiber, in the case of a fiber with a non-circular cross-sectional shape, the average value of the diameters of the circumscribed circle and the inscribed circle of the non-circular cross-section is taken as the diameter of the fiber.

[0044] The fiber layer 30 can be composed of one or more fibers 40. The fiber 40 may be composed of a fiber bundle of a plurality of fibers. The form of the fiber bundle is not particularly limited and may be twisted, untwisted, or non-twisted. The number of fibers in the fiber bundle may be, for example, 2 or more and 10 or less.

[0045] The fiber layer 30 may be composed of one type of fiber 40. For example, the fiber layer 30 may be composed only of fibers containing a biodegradable polymer material and a drug, or may be composed only of fibers containing a non-biodegradable polymer material and a drug.

[0046] The fiber layer 30 may be composed of a plurality of types of fibers 40. For example, the fiber layer 30 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.

[0047] The fiber 40 may be a hollow fiber, but is preferably a solid fiber. The fiber 40 may or may not have crimps. A fiber having crimps refers to, for example, a solid fiber having a three-dimensional crimp structure in a spiral shape.

[0048] The single fiber 40 may have a straight shape extending straight or a shape branched in the middle.

[0049] The fiber layer 30 may extend in the radial direction y. For example, as the tubular body 10 expands, the fiber layer 30 may extend in the radial direction y.

[0050] The average fiber diameter of the fiber 40 is preferably 1 nm or more, 10 nm or more, 100 nm or more, 1 μm or more. To prevent the outer diameter of the fiber layer 30 from becoming excessively large, the average fiber diameter of the fiber 40 is preferably 50 μm or less, 45 μm or less, 40 μm or less.

[0051] The average fiber length of the fiber 40 may be, for example, 100 mm or more, 200 mm or more, 300 mm or more, or may be 1300 mm or less, 1200 mm or less, 1100 mm or less, 1000 mm or less.

[0052] The average fiber length of the fiber 40 can be measured by the following method. Ten arbitrary single fibers are taken out from the fiber layer 30. Each fiber is stretched straight without elongation, and the fiber length (mm) is measured on a ruler. The average value of the measured fiber lengths of the 10 fibers is taken as the average fiber length of the fiber 40. When the number of fibers constituting the fiber layer 30 is less than 10, the fiber lengths of all the fibers constituting the fiber layer 30 are measured, and the average value of the measured fiber lengths is taken as the average fiber length of the fiber 40. When the number of fibers constituting the fiber layer 30 is 1, the fiber length of that 1 fiber is taken as the average fiber length of the fiber 40. When the fiber to be measured is branched, for example, having a first branch portion and a second branch portion, the longer one of the first branch portion and the second branch portion is used for calculating the fiber length.

[0053] The fiber 40 can be formed using, for example, an electrospinning method, a melt spinning method, a wet spinning method, or a dry spinning method. Among them, it is preferably formed using the electrospinning method. When forming the fiber layer 30 by the electrospinning method, by using the tubular body 10 as a collector of the electrospinning system and spinning while rotating the tubular body 10, the fiber 40 can be wound around the outer peripheral surface of the tubular body 10.

[0054] The fibers 40 contained in the fiber layer 30 contain a polymer material 41 and a drug 42. Preferably, the fiber layer 30 does not contain any other components besides the fibers 40, such as thread-like materials with an average fiber diameter of more than 100 μm, resin wires, metal wires, etc.

[0055] Preferably, the fiber layer 30 is composed only of fibers 40 containing a polymer material 41 and a drug 42.

[0056] The polymer contained in the polymer material 41 may be a synthetic polymer or a natural polymer. The polymer material 41 also includes resins.

[0057] 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.

[0058] 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) (PHH 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.

[0059] 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.

[0060] 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.

[0061] In addition to the materials described above, the polymer material 41 may also contain various additives such as plasticizers, pigments, flame retardants, antistatic agents, lubricants, softeners, surfactants, and antibacterial agents.

[0062] 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.

[0063] 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). Examples include anticoagulants (such as Jar), ​​N-acetyl-L-cysteine ​​(NAC), calcium channel blockers (such as amlodipine, nifedipine, and diltiazem), diuretics (such as furosemide, trichlormethiazide, and spironolactone), angiotensin-converting enzyme inhibitors (ACEs) (such as enalapril, lisinopril, and perindopril), beta-blockers (such as metoprolol, atenolol, and bisoprolol), alpha-blockers (such as prazosin, terazosin, and doxazosin), alpha-beta-blockers (such as carvedilol, labetalol, and butoxamine), nitrates (such as nitroglycerin and isosorbide dinitrate), prostacyclin analogs (such as epoprostenol and treprostinil), anticoagulants (such as heparin, heparin derivatives, warfarin, antithrombin drugs such as dabigatran, and rivaroxaban), and antiplatelet agents (such as aspirin, clopidogrel, and ticagrelor).

[0064] 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 also 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.

[0065] The fiber layer 30 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.

[0066] 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, tantalum, and the like.

[0067] 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.

[0068] As shown in Figure 6, 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.

[0069] The fiber 40 shown in Figure 6 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.

[0070] 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.

[0071] 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, preferably 80 wt% or less, more preferably 70 wt% or less, and even more preferably 60 wt% or less.

[0072] 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, preferably 80 wt% or less, more preferably 70 wt% or less, and even more preferably 60 wt% or less.

[0073] 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.

[0074] 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 a concentric core-sheath structure and an eccentric core-sheath structure. 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 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.

[0075] As shown in Figure 7, 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.

[0076] 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 and a second branch portion, then in the first branch portion and / or the second branch portion, the core portion 44 may be exposed without being covered by the sheath portion 45.

[0077] 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.

[0078] In the core portion 44, the content of the drug 42 is preferably 80 wt% or more, more preferably 90 wt% or more, even more preferably 95 wt% or more, and may be 100 wt% or less, 99 wt% or less, or 98 wt% or less.

[0079] 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.

[0080] In the sheath portion 45, the content of the polymer material 41 is preferably 80 wt% or more, more preferably 90 wt% or more, even more preferably 95 wt% or more, and may be 100 wt% or less, 99 wt% or less, or 98 wt% or less.

[0081] The fiber layer 30 is preferably composed of one or more core-sheath type fibers.

[0082] 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.

[0083] 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.

[0084] In the implantation device 1, the degree of orientation of the fibers 40 in the fiber layer 30, as measured by the following method, is 60% or more. (Method) An image 60 of the tubular body 10 viewed from the side, as shown in Figure 8, is obtained, and for each of the 20 target fibers 61 selected in the image 60, the relative angle θ (0° < θ ≤ 180°) of the direction of extension m of the target fiber 61 with respect to the direction x1 parallel to the longitudinal direction x of the tubular body 10 is measured. The angle θ is classified into 10 classes obtained by equally dividing the range greater than 0° and less than or equal to 180°, and the frequency distribution for each class is obtained. The quantity ratio (%) of the sum of the frequencies of two adjacent classes to the total frequency is the degree of orientation of the fibers 40. Here, the first and tenth classes are considered to be adjacent. A specific example of the method for measuring the degree of orientation of the fibers 40 is described below.

[0085] (Step S1: Acquisition of images for evaluation) An image 60 of the tubular body 10 viewed from the side is acquired, as shown in Figure 8. Image 60 is obtained by scanning an electron microscope or laser microscope (for example, a scanning transmission electron microscope (STEM-EDX / EELS) HD-2700 manufactured by Hitachi High-Technologies Corporation) and photographing the fiber layer 30 from a direction perpendicular to the longitudinal direction x of the tubular body 10 at a magnification of 1000x. An example of the acquired image 60 is shown in Figure 8. The length of image 60 in the vertical direction (parallel to the radial direction y) and the length of image 60 in the horizontal direction (parallel to the longitudinal direction x) are made to be the same size. The size of image 60 may be, for example, 100 μm vertically and 100 μm horizontally. If the sizes in the vertical and horizontal directions are different, the image 60 is cropped.

[0086] Image 60 may be an image of any part of the fiber layer 30. For example, Image 60 may be an image of the distal part of the fiber layer 30, or an image of the proximal part of the fiber layer 30, but it is preferable that the image passes through the central position 14 in the longitudinal direction x of the fiber layer 30 (see Figures 3 and 5), and it is more preferable that the lateral center position of Image 60 coincides with the central position 14 in the longitudinal direction x of the fiber layer 30.

[0087] (Step S2: Selection of Fibers to be Measured) The 20 fibers in image 60 are designated as the fibers to be measured 61. As shown in Figure 8, the extension direction m of the fibers to be measured 61 is defined by the extension direction of the line segment (straight line) connecting the start point 62 and the end point 63 of the fibers to be measured 61. The 20 fibers to be measured 61 are selected in order from the longest to the shortest in image 60. The fibers to be measured 61 only need to have their start point 62 and end point 63 visible in image 60, and in parts not shown in image 60, the start point 62 or end point 63 may be connected to other fibers, or the fiber may branch midway. If the fiber branches midway, the start point 62 and end point 63 may be defined using the branch with the longest fiber length among the multiple branches formed by the branching. For example, the fiber 61 shown in Figure 9 has a branching portion 64, which has a first branch 61a and a second branch 61b, with the first branch 61a being longer than the second branch 61b. Therefore, in the fiber 61 shown in Figure 9, the length of the starting point 62, the ending point 63, and the line segment connecting them are defined using the first branch 61a, which is longer than the second branch 61b.

[0088] (Step S3: Measurement of angle θ) For each of the 20 fibers 61 to be measured, the relative angle θ of the direction of extension m of the fiber 61 with respect to the direction x1 parallel to the longitudinal direction x of the tubular body 10 is measured. θ is in the range of greater than 0° and less than or equal to 180°. The angle θ is classified into 10 classes obtained by dividing the range of greater than 0° and less than or equal to 180° in 18° increments, and the frequency distribution for each class is determined. Table 1 shows the 10 classes, from class 1 to class 10. The numerical ratio (%) of the sum of the frequencies of two adjacent classes to the total frequency is taken as the degree of orientation of the fiber 40. Here, the 1st and 10th classes are considered to be adjacent.

[0089]

[0090] In this specification, the degree of orientation of the fibers 40 in the fiber layer 30 measured by the above method is 60% or more. That is, in the above method, 12 or more of the total 20 fibers 61 to be measured in the image 60 are located in two adjacent classes. More specifically, 60% of the fibers 40 in the fiber layer 30 measured by the above method are classified into one of the following: (i) class 1 or class 2, (ii) class 2 or class 3, (iii) class 3 or class 4, (iv) class 4 or class 5, (v) class 5 or class 6, (vi) class 6 or class 7, (vii) class 7 or class 8, (viiii) class 8 or class 9, (ix) class 9 or class 10, or (x) class 10 or class 1. As a result, the fibers 40 in the fiber layer 30 are oriented in a specific direction, making it easier to uniformly release the drug contained in the fibers 40 over a wide area of ​​the fiber layer 30.

[0091] For example, if there are 2 fibers each classified as class 1 and 5, 6 fibers each classified as class 2, 7 fibers each classified as class 3, 1 fiber each classified as class 6, 9, and 10, and 0 fibers each classified as class 7 and 8, then the degree of orientation of the fibers 40 in the fiber layer 30 is 65%. This can be calculated using the formula: (6 + 7, which is the sum of the frequencies classified as class 2 and 3) × 100 / (20, which is the total number of fibers 61 to be measured).

[0092] The degree of orientation of the fibers 40 in the fiber layer 30 measured by the above method may be 60% or more, preferably 65% ​​or more, more preferably 70% or more, and even more preferably 80% or more. Furthermore, the degree of orientation of the fibers 40 in the fiber layer 30 measured by the above method may be 100% or less, 95% or less, or 90% or less. As a result, the fibers 40 in the fiber layer 30 are more oriented in a specific direction, making it easier to uniformize the release rate of the drug contained in the fibers 40 over a wide area of ​​the fiber layer 30.

[0093] It is preferable that the average fiber length of the fibers 40 is 100 mm or more, and that in the fiber layer 30, the fibers 40 are wound around the outer surface 12 of the tubular body 10. This arrangement of the fiber layer 30 makes it easier to orient the fibers 40 within the fiber layer 30 in a specific direction.

[0094] As shown in Figure 10, it is preferable that the fibers 40 contained in the fiber layer 30 are oriented in the longitudinal axis direction p of the wire 21. More specifically, it is preferable that 60% or more of the total 20 measurement target fibers 61 in Image 60, i.e., 12 or more fibers, are within ±5° of the longitudinal axis direction p of the wire 21. As a result, many fibers 40 extend along the longitudinal axis direction p, and the fibers 40 can easily pass between adjacent wires 21 in the longitudinal direction x of the tubular body 10 and enter the lumen 11 of the tubular body 10. The entry of fibers 40 into the lumen 11 can improve the sustained release of the drug 42. In addition, since the fibers 40 can easily follow the longitudinal axis direction p of the wire 21, it is easier to obtain a rigid tubular body 10. Note that a rigid tubular body 10 means that the bending rigidity of the tubular body 10 is high.

[0095] The gap between adjacent wires 21 in the longitudinal direction x may be an extremely narrow gap relative to the outer diameter of the wire 21, for example, 1 nm to 100 μm. Preferably, the gap between the wires 21 is narrow enough for the fibers 40 to pass through.

[0096] As shown in Figure 11, it is preferable that the fibers 40 contained in the fiber layer 30 are oriented in a direction q perpendicular to the longitudinal axis direction p of the wire 21. More specifically, it is preferable that 60% or more of the total 20 measured fibers 61 in Image 60, i.e., 12 or more fibers, are within a range of ±5° with respect to direction q. This makes it difficult for fibers 40 to penetrate between adjacent wires 21 in the longitudinal direction x of the tubular body 10, thus preventing the bending and flexing movements of the tubular body 10 from being restricted by the fiber layer 30. As a result, the tubular body 10 becomes flexible and is suitable for use in the phase of filling a tubular body into a knot.

[0097] As shown in Figures 2-3 and 5, it is preferable that the fiber layer 30 is arranged over the entire length x of the tubular body 10. Since the flexibility of the tubular body 10 tends to decrease when the fiber layer 30 is provided, the fiber layer 30 may be arranged only in a part of the length x of the tubular body 10. For example, the fiber layer 30 may be arranged in a section of 30% or more of the total length x of the tubular body 10, 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 30 may be arranged in a section of 90% or less of the total length x of the tubular body 10, or in a section of 80% or less of the total length, or in a section of 70% or less of the total length.

[0098] The length of the fiber layer 30 in the longitudinal direction x is preferably the same as or shorter than the length of the tubular body 10 in the longitudinal direction x. The fiber layer 30 is preferably not located distal to the distal end of the tubular body 10. Furthermore, the fiber layer 30 is preferably not located proximal to the proximal end of the tubular body 10.

[0099] As shown in Figure 12, the fiber layer 30 is located only in the distal portion 10D of the tubular body 10 and does not need to be located in the proximal portion 10P of the tubular body 10. As shown in Figure 13, the fiber layer 30 is located only in the proximal portion 10P of the tubular body 10 and does not need to be located in the distal portion 10D of the tubular body 10.

[0100] As shown in Figure 14, when the length of the tubular body 10 is divided into three equal parts in the longitudinal direction x of the tubular body 10 into a distal section 10A, a central section 10B, and a proximal section 10C, the fiber layer 30 may be located only in the central section 10B, or as shown in Figure 15, it may be located in the distal section 10A and the central section 10B but not in the proximal section 10C, or, although not shown, it may be located in the proximal section 10C and the central section 10B but not in the distal section 10A.

[0101] As shown in Figure 16, it is preferable that the fiber layer 30 is not provided at the distal end of the tubular body 10. For example, if the tubular body 10 is a coil 15, and the wire 21 that is not covered by the tip 25 and is at the most distal end of the coil 15 is counted as the first turn from the distal side of the coil 15, it is preferable that the fiber layer 30 is positioned proximal to the third turn of the coil 15 from the distal side, more preferably proximal to the fifth turn of the coil 15 from the distal side, and even more preferably proximal to the tenth turn of the coil 15 from the distal side. By not providing the fiber layer 30 at the distal end of the coil 15, the outer surface 12 of the coil 15 is more easily exposed at the distal end, which makes it easier for the coil 15 to firmly engage with other parts of the coil and other coils when placed in the knot, making it easier to form a framework.

[0102] As shown in Figure 16, it is preferable that the fiber layer 30 is not provided at the proximal end of the tubular body 10. For example, if the tubular body 10 is a coil 15, and the wire 21 that is not covered by the base tip 26 and is at the nearest position in the coil 15 is counted as the first turn from the proximal side of the coil 15, it is preferable that the fiber layer 30 is located distal to the third turn of the coil 15, more preferably distal to the fifth turn of the coil 15, and even more preferably distal to the tenth turn of the coil 15. By not providing the fiber layer 30 at the proximal end of the coil 15, the outer surface 12 of the coil 15 is more easily exposed at the proximal end, which helps to prevent a decrease in the flexibility of the coil 15.

[0103] As shown in Figure 16, it is preferable that the fiber layer 30 is arranged only in the portion of the tubular body 10 excluding the distal and proximal ends.

[0104] Although not shown in the figures, the fiber layer 30 may not be provided at the distal end of the tubular body 10, nor at the proximal portion 10P of the tubular body 10, and the fiber layer 30 may be provided only at the portion of the tubular body 10 excluding the distal end and the proximal portion 10P. This makes it easier to engage the distal end of the tubular body 10 with other members while preventing a decrease in flexibility at the proximal portion 10P of the tubular body 10.

[0105] When the tubular body 10 is composed of wires 21, it is preferable that the fibers 40 are sandwiched between two adjacent wires 21 in the longitudinal direction x, as shown in Figures 17 to 18. By sandwiching the fibers 40 between the wires 21, the drug 42 is less likely to be released from the fibers 40 in the sandwiched portion, thereby improving the sustained release of the drug.

[0106] As shown in Figures 17 and 18, if there is a gap 22 between adjacent wires 21 in the longitudinal direction x, some of the fibers of the fiber layer 30 may be placed in the gap 22. Here, the gap 22 is defined as having a length in the longitudinal direction x that is 1 / 10 or larger than the outer diameter of the wire 21.

[0107] Although not shown in the diagram, even if there is a gap 22 between adjacent wires 21 in the longitudinal direction x, the fiber layer 30 does not need to be placed in the gap 22.

[0108] As shown in Figures 3 and 5, the fiber layer 30 may be arranged only on the radially y-outside of the outermost position of the outer circumferential surface 12 of the tubular body 10.

[0109] As shown in Figures 17 and 18, the fiber layer 30 may be positioned radially y inward from the outermost position of the outer surface 12 of the tubular body 10.

[0110] As shown in Figure 18, the fiber layer 30 may be arranged on the inner circumferential surface 13 side of the tubular body 10. That is, the fibers 40 of the fiber layer 30 may be present in the lumen 11 of the tubular body 10. Since the drug 42 is less likely to be released from the fibers 40 arranged in the lumen 11 compared to the fibers 40 arranged on the outer circumferential surface 12, the sustained release of the drug can be improved.

[0111] As can be seen from Figure 18, if there is a gap 22 between adjacent wires 21 in the longitudinal direction x, the fiber layer 30 may enter the lumen 11 of the tubular body 10 through the gap 22.

[0112] The tubular body 10 shown in Figure 18 may be formed by providing a fiber layer 30 on the outer surface of a wire 21, and then winding the wire 21 with the fiber layer 30 to form a coil shape.

[0113] Although not shown in the diagram, the second agent may be impregnated into the interfiber gaps of the fiber layer 30. This allows the fiber layer 30 to hold a large amount of the agent while preventing an initial burst of the agent. For the composition of the second agent, please refer to the description of agent 42.

[0114] The surface roughness Ra of the outer circumferential surface 12 of the tubular body 10 may be greater than the surface roughness Ra of the inner circumferential surface 13 of the tubular body 10. This increases the frictional force acting between the outer circumferential surface 12 of the tubular body 10 and the inner circumferential surface 33 of the fiber layer 30, making it easier for the fiber layer 30 to adhere tightly to the outer circumferential surface 12 of the tubular body 10. The surface roughness Ra of the outer circumferential surface 12 and the inner circumferential surface 13 of the tubular body 10 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. When measuring the calculated average roughness Ra of a tubular body 10 that already has a fiber layer 30, the fiber layer 30 can be removed from the tubular body 10 before measurement. The fiber layer 30 can be removed by dissolving it in a solvent such as physiological saline.

[0115] If the tubular body 10 is a coil 15, when measuring the surface roughness Ra, the wire 21 constituting the coil 15 (primary coil) can be straightened by gripping both ends of the wire 21, or the distal end of the wire 21 and a position several centimeters proximal to the distal end (for example, 5 cm proximal to the distal end), and pulling it. The surface roughness of the straightened wire 21 can then be measured in accordance with JIS B 0633 (2001). Similarly, if the coil 15 (primary coil) has been shaped to form a secondary coil, the wire 21 constituting the secondary coil can be straightened by gripping both ends of the wire 21, or the distal end of the wire 21 and a position several centimeters proximal to the distal end (for example, 5 cm proximal to the distal end), and pulling it. The surface roughness of the straightened wire 21 can then be measured in accordance with JIS B 0633 (2001). The surface roughness Ra of the outer surface of the coil 15 (primary coil) can be determined by measuring the surface roughness Ra of the portion of the straightened wire 21 that corresponds to the outer surface of the coil 15 (primary coil). Similarly, the surface roughness Ra of the inner surface of the coil 15 (primary coil) can be determined by measuring the surface roughness Ra of the portion of the straightened wire 21 that corresponds to the inner surface of the coil 15 (primary coil). Since the coil 15 is constructed by winding the wire 21, the area of ​​the outer circumference of the straightened wire 21, for example, between 0° and 180°, corresponds to the outer surface of the coil 15, and the area of ​​the outer circumference of the straightened wire 21, for example, between 180° and 360°, corresponds to the inner surface of the coil 15. Therefore, by measuring the surface roughness Ra of the wire 21, the surface roughness Ra of the coil 15 can be measured.

[0116] Although not shown in the figures, in addition to the fiber layer 30, a drug may be placed on the surface of the tubular body 10. In that case, the drug may be placed on the outer surface 12 or on the inner surface 13. The drug placed on the surface of the tubular body 10 may be held on the surface of the tubular body 10 as a drug layer. A drug layer may be placed on the outer surface 12 of the tubular body 10, and the fiber layer 30 may be placed outside the drug layer in the radial direction y.

[0117] In addition to the fiber layer 30, the drug applied to the tubular body 10 may be directly attached to the surface of the tubular body 10, or it may be attached indirectly to the surface of the tubular body 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.

[0118] If the drug is directly attached to the surface of the tubular body 10, the drug may be covered by the fiber layer 30 in order to control the rate of drug release.

[0119] In addition to the fiber layer 30, the drug applied to the tubular body 10 is preferably encapsulated. The drug encapsulated in the capsule may be directly attached to the surface of the tubular body 10, or it may be attached indirectly to the surface of the tubular body 10 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.

[0120] As shown in Figures 2 and 19, when the primary coil is extended in a straight line with the distal end of the primary coil on the left and the proximal end on the right, the wire 21 extends at an angle with respect to the radial direction y (the vertical direction in the plane of the paper in Figures 2 and 19). As shown in Figure 2, when the wire 21 extends from the top to the bottom as it goes from the distal end to the proximal end of the tubular body 10, the longitudinal axis p of the wire 21 has a negative slope. As shown in Figure 19, when the wire 21 extends from the bottom to the top as it goes from the distal end to the proximal end of the tubular body 10, the longitudinal axis p of the wire 21 has a positive slope. Similarly, with respect to the fibers 40 contained in the fiber layer 30, if they extend from the top to the bottom as you move from the distal to the proximal side of the tubular body 10, the direction of extension of the fibers 40 is assumed to have a negative slope, and if they extend from the bottom to the top as you move from the distal to the proximal side of the tubular body 10, the direction of extension of the fibers 40 is assumed to have a positive slope. In this case, the sign of the slope in the longitudinal axis direction p of the wire 21 and the sign of the slope in the direction of extension of the fibers 40 may be different or the same. For example, if the longitudinal axis direction p of the wire 21 has a negative slope, the direction of extension of the fibers 40 in the fiber layer 30 may have a negative slope or a positive slope. Also, if the longitudinal axis direction p of the wire 21 has a positive slope, the direction of extension of the fibers 40 in the fiber layer 30 may have a positive slope or a negative slope.

[0121] Preferably, 60% or more of the fibers 40 in the fiber layer 30 have the same sign of inclination in the longitudinal axis direction p of the wire 21 as the sign of inclination in the direction of extension of the fibers 40, more preferably 70% or more have the same sign, and even more preferably 80% or more have the same sign. Furthermore, preferably 100% or less of the fibers 40 in the fiber layer 30 have the same sign of inclination in the longitudinal axis direction p of the wire 21 as the sign of inclination in the direction of extension of the fibers 40, more preferably 95% or less have the same sign, and even more preferably 90% or less have the same sign. The percentage (%) of the fibers 40 in the fiber layer 30 in which the sign of inclination in the longitudinal axis direction p of the wire 21 and the sign of inclination in the direction of extension of the fibers 40 are the same can be calculated from the image 60 described above using 20 target fibers 61 for measuring the relative angle θ of the extension direction m of the target fiber 61 with respect to the direction x1 parallel to the longitudinal direction x of the tubular body 10. For example, for each of the 20 fibers 61 to be measured, the sign of the inclination in the longitudinal axis direction p of the wire 21 and the sign of the inclination in the extension direction m of the fiber 61 to be measured can be examined, and by using (number of fibers 61 to be measured that have the same sign of inclination as the inclination in the longitudinal axis direction p of the wire 21) × 100 / (total number of fibers 61 to be measured, which is 20), the proportion of the inclination in the longitudinal axis direction p of the wire 21 and the inclination in the extension direction of the fiber 40 that have the same sign can be determined.

[0122] It is preferable that 60% or more of the fibers 40 in the fiber layer 30 have different signs for the inclination of the wire 21 in the longitudinal axis direction p and the inclination of the fiber 40 in the direction of extension, more preferably 70% or more have different signs, and even more preferably 80% or more have different signs. Furthermore, it is preferable that 100% or less of the fibers 40 in the fiber layer 30 have different signs for the inclination of the wire 21 in the longitudinal axis direction p and the inclination of the fiber 40 in the direction of extension, more preferably 95% or less have different signs, and even more preferably 90% or less have different signs. The percentage (%) of the fibers 40 in the fiber layer 30 in which the sign of the inclination of the wire 21 in the longitudinal axis direction p and the sign of the inclination of the fiber 40 in the direction of extension are different can be calculated from the image 60 described above using 20 target fibers 61 for measuring the relative angle θ of the extension direction m of the target fiber 61 with respect to the direction x1 parallel to the longitudinal direction x of the tubular body 10. For example, for each of the 20 fibers 61 to be measured, the sign of the inclination in the longitudinal axis direction p of the wire 21 and the sign of the inclination in the extension direction m of the fiber 61 to be measured can be examined, and by using (number of fibers 61 to be measured that have an inclination with a different sign from the inclination in the longitudinal axis direction p of the wire 21) × 100 / (total number of fibers 61 to be measured, which is 20), the proportion of the inclination in the longitudinal axis direction p of the wire 21 and the inclination in the extension direction of the fiber 40 that are different in sign can be determined.

[0123] Although not shown in the figures, if the inclination of the wire 21 in the longitudinal direction p changes along the longitudinal direction x of the tubular body 10, for example, in either the section with a first inclination along the longitudinal direction x or the section with a second inclination along the longitudinal direction x, it is preferable that 60% to 100% of the fibers 40 of the fiber layer 30 have the same or different signs for the inclination of the wire 21 in the longitudinal direction p and the inclination of the fibers 40 in the direction of extension. In such cases where there are two sections in the longitudinal direction x where the inclination of the wire 21 in the longitudinal direction p differs, the signs for the inclination of the wire 21 in the longitudinal direction p and the signs for the inclination of the fibers 40 in the direction of extension can be determined by using an image that passes through the center position of each section in the longitudinal direction x.

[0124] As shown in Figure 3, it is preferable that the retaining device 1 has a stretch resistance member 50 positioned in the lumen 11 of the coil 15. The stretch resistance member 50 suppresses the stretching of the coil 15 in the longitudinal direction x during operation.

[0125] The stretch resistance member 50 may be a long member made of a single wire or stranded wire. The stretch resistance member 50 can be linear, wavy, helical, or a combination thereof. Only one or more stretch resistance members 50 may be placed in the lumen 11. The stretch resistance member 50 may be made of resin or metal.

[0126] The first end of the stretch resistance member 50 may be connected to the distal end of the coil 15 (for example, the distal end of the wire 21). The second end of the stretch resistance member 50 may be connected to the proximal end of the coil 15 (for example, the proximal end of the wire 21) or to the connection portion 53. The stretch resistance member 50 may be placed in the lumen 11 in a state where it is folded back midway along the longitudinal axis of the stretch resistance member 50.

[0127] Methods for connecting the stretch resistance member 50 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.

[0128] As shown in Figures 1 and 3, the retaining device 1 is positioned proximal to the coil 15 in the longitudinal direction x of the coil 15 and may further include a pusher 55 that pushes the coil 15 distally and a connecting portion 53 that connects the proximal portion of the coil 15 and the distal portion of the pusher 55.

[0129] The pusher 55 is a rod-shaped or wire-shaped member used to hold the coil 15 and push it distally. The pusher 55 can consist of one or more members. The pusher 55 can consist of a wire member, a coil member, or a combination thereof. The pusher 55 can be made of a conductive material such as stainless steel.

[0130] The connection portion 53 connects the coil 15 and the pusher 55. Preferably, the connection portion 53 has a detachment mechanism that allows the coil 15 to detach from the pusher 55. Examples of detachment mechanisms include hydraulic, electric, and mechanical types, and among these, an electric detachment mechanism is preferred. In the detachment mechanism, it is preferable that the connection portion 53 is heated and disconnected by electrical or thermal energy supplied through the pusher 55, causing the coil 15 to detach from the pusher 55. In this case, it is preferable that the connection portion 53 is heated by a high-frequency current supplied between the distal end of the pusher 55 and the counter electrode.

[0131] The connecting portion 53 preferably contains a material that melts or dissolves when heated. The connecting portion 53 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.

[0132] As shown in Figures 1 to 3, the coil 15 is constructed by winding a wire 21, and the implantation device 1 may further have a tip 25 positioned at the distal end of the coil 15. The tip 25 covers a portion of the wire 21 to prevent the distal end of the wire 21 from directly contacting the inner wall surface of the body.

[0133] As shown in Figures 1 to 3, a proximal tip 26 may be provided at the proximal end of the coil 15 to close the proximal end of the coil 15. The proximal tip 26 has a lumen, and a part of the connecting portion 53, for example, the distal end, may be inserted into the lumen.

[0134] The tip 25 and / or base tip 26 may be made of a metal material or a 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 metal that constitutes the tip 25 can be one of the metals mentioned in the description of the wire 21.

[0135] In the longitudinal direction x, it is preferable that the fiber layer 30 is positioned distal to the distal end of the connecting portion 53. In the longitudinal direction x, it is preferable that the fiber layer 30 is not positioned in the portion where the coil 15 and the connecting portion 53 overlap.

[0136] This application claims the benefit of priority based on Japanese Patent Application No. 2025-17311, filed on 5 February 2025. The entire specification of Japanese Patent Application No. 2025-17311, filed on 5 February 2025, is incorporated herein by reference.

[0137] 1: Intraviviparous device 10: Tubular body 11: Lumen 12: Outer surface 13: Inner surface 15: Coil 16: Stent 21: Wire 22: Gap 25: Tip 26: Proximal tip 30: Fiber layer 31: Lumen 32: Outer surface 33: Inner surface 40: Fiber 41: Polymer material 42: Drug 44: Core 45: Sheath 50: Stretch resistance member 53: Connection part 55: Pusher 60: Image 61: Fiber to be measured 62: Start point 63: End point θ: Relative angle of the extension direction of the fiber to be measured with respect to the direction parallel to the longitudinal direction of the tubular body m: Extension direction of the fiber to be measured p: Longitudinal axis direction of the wire q: Direction perpendicular to the longitudinal axis direction of the wire x: Longitudinal direction of the tubular body x1: Direction parallel to the longitudinal direction of the tubular body y: radial direction of the tubular body z: circumferential direction of the tubular body

Claims

1. An in-vivo implant comprising: a tubular body having a longitudinal direction; and a fiber layer disposed on the outer surface of the tubular body, wherein the fiber layer contains fibers comprising a polymer material and a drug, and the degree of orientation of the fibers in the fiber layer, as measured by the following method, is 60% or more. (Method) An image of the tubular body viewed from the side is obtained, and for each of the 20 target fibers selected in the image, the relative angle θ (0° < θ ≤ 180°) of the direction of extension of the target fiber with respect to the direction parallel to the longitudinal direction is measured. The relative angle θ is classified into 10 classes obtained by equally dividing the range greater than 0° and less than or equal to 180°, and the frequency distribution for each class is obtained. The numerical ratio (%) of the sum of the frequencies of two adjacent classes to the total frequency is the degree of orientation of the fibers. Here, the first and tenth classes are considered to be adjacent.

2. The in-vivo implantation 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 in-vivo implantation device according to claim 1 or 2, wherein the degree of orientation of the fibers in the fiber layer is 80% or more.

4. The in-vivo implantation device according to claim 1 or 2, wherein the average fiber length of the fibers is 100 mm or more, and in the fiber layer, the fibers are wound around the outer surface of the tubular body.

5. The in-vivo implantation device according to claim 1 or 2, wherein the tubular body is a coil formed by winding a long wire.

6. The in-vivo implantation device according to claim 5, wherein the fibers are oriented in the longitudinal axis direction of the wire.

7. The in-vivo implantation device according to claim 5, wherein the fibers are oriented in a direction perpendicular to the longitudinal axis of the wire.

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

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