JP2024057621A - In vivo indwelling device and its manufacturing method - Google Patents

Abstract

[Problem] To provide an in-vivo implantable device and a manufacturing method thereof that prevents in-vivo tissue from entering the voids at the end of the stent cover, thereby reducing the risk of damage to the stent cover and falling off of the stent. [Solution] An in-vivo implantable device (10) having a tubular stent (20), a tubular stent cover (30) formed of fibers (31) with voids (32), and a filling element (40) that fills at least a part of the voids (32) of the stent cover (30), the voids (32) are areas surrounded by the fibers (31) and are arranged continuously in the circumferential and axial directions over the entire circumference and length, the voids (32) located at the axial end of the stent cover (30) and arranged in the circumferential direction are defined as end voids (35), and the filling element (40) fills at least a part of the end voids (35). [Selected Figure] Figure 2

Description

The present invention relates to an in vivo indwelling device and a method for manufacturing the same.

A known method for treating lesions in biological lumens such as blood vessels is to percutaneously introduce a treatment device such as a catheter into the biological lumen and treat the lesion from within the biological lumen. In such treatment methods, when the lesion is a stenosis, the stenosis is expanded with a balloon, and a stent, which is an implantable medical device, is often placed to prevent restenosis after the balloon expansion. The surface of the stent is often coated with a drug that inhibits the migration and proliferation of vascular smooth muscle cells, which are the cause of restenosis. Such drug-coated stents are known as drug-eluting stents.

A stent has a tubular structure in which struts, which are linear components, are formed in a wavy and circular pattern, allowing it to contract and expand radially. When placing a stent at a lesion, the surgeon delivers the catheter on which the stent is contracted to the lesion. After the stent reaches the lesion, the surgeon manipulates the catheter to expand the stent and place it at the lesion.

If plaque is present at the lesion site where the stent is to be placed, the struts may be pressed against the plaque as the stent expands, causing cracks in the plaque and debris to form. As a result, the debris passes between the struts and migrates into the bloodstream, and in some cases is trapped in the peripheral blood vessels, causing the peripheral blood vessels to become occluded and causing necrosis of the peripheral tissue.

Patent Document 1 proposes an in-vivo device in which a stent is covered with a stent cover having voids, which is a woven fabric with woven fibers or a knitted fabric with woven fibers. The area surrounded by fibers, which corresponds to the voids in the stent cover, is smaller than the area surrounded by struts, which corresponds to the gaps in the stent. Therefore, debris generated by the compression of the struts is trapped in the stent cover, and migration of the debris into the blood is prevented. In addition, since the stent cover has voids, endothelial cells infiltrate through the voids in the stent cover after placement of the in-vivo device. Therefore, endothelialization occurs earlier than when the stent cover does not have voids, reducing the risk of thrombosis.

U.S. Pat. No. 1,007,0976

The woven fabric as a stent cover with voids is formed by intersecting weft and warp fibers, and has a structure in which voids surrounded by the weft and warp fibers are connected in the circumferential and axial directions. Normally, a specific fiber surrounding any void does not protrude radially outward due to the constraints of the intersecting fibers. However, the fibers surrounding a void present at the axial end of the fabric may spread radially outward if the end of the fiber extending in the axial direction that is not constrained by the intersecting fibers spreads radially outward. If a biological tissue or the like gets caught in a void in a fiber that spreads radially outward during catheter delivery, there is a risk of the fabric being damaged or the stent falling off.

In addition, in the knit as a stent cover having voids, the fibers are alternately folded back to form loops and are continuous in the circumferential direction, so that the loops are continuous in the circumferential direction. Also, a specific loop when the fibers are woven and a loop formed at the same circumferential position after an arbitrary number of loops are continuous intersect while being shifted in the axial direction. With the fibers continuing in this way, the knit has a spiral structure in which loops are connected in the circumferential direction and the axial direction. Therefore, any loop, except for the loop at the axial end of the knit, is restrained by the loops adjacent on both sides in the axial direction. However, since the loop at the axial end does not have an adjacent loop on one side in the axial direction, the loop may spread outward in the radial direction. If the loops that spread outward in the radial direction get caught on in vivo tissue during catheter delivery, there is a risk of the knit being damaged or the stent falling off.

In terms of fiber form, knitted fabrics have better expandability and contractibility than woven fabrics. On the other hand, the risk of loops at the ends of knitted fabrics spreading outward in the radial direction is higher than the risk of fibers surrounding voids at the axial end of woven fabrics spreading outward in the radial direction. This is because, in the case of woven fabrics, the ends of the fibers extending in the axial direction are located closer to the end than the fibers surrounding the voids at the axial end of the woven fabric, and the fibers surrounding the voids at the axial end of the woven fabric are themselves restrained by the intersecting fibers.

The present invention has been made to solve the above-mentioned problems, and aims to provide an in-vivo device and a manufacturing method thereof that prevents in-vivo tissue from entering the gap at the end of the stent cover and reduces the risk of damage to the stent cover and detachment of the stent.

The in-vivo implant that achieves the above-mentioned object comprises a tubular stent that extends in the axial direction, has a tip and a base end, is formed so as to be capable of radial expansion and contraction, and has gaps; a tubular stent cover that extends in the axial direction, has a tip and a base end, is formed so as to be capable of radial expansion and contraction, has gaps, and is formed of fibers; and a filling element that fills at least a part of the gaps in the stent cover, the gaps in the stent cover being an area surrounded by the fibers, and are arranged continuously in a line in the circumferential and axial directions over the entire circumference and length, the gaps located at the ends of the axial direction of the stent cover and arranged in the circumferential direction are defined as end gaps, and the filling element is characterized in that at least a part of the end gaps is filled.

The in-vivo implant device configured as described above has a filling element filled in at least some of the end gaps at the axial end of the stent cover, which prevents undesirable radial outward expansion of the axial end of the stent cover and prevents in-vivo tissue from entering the end gaps, thereby reducing the risk of damage to the stent cover and detachment of the stent.

The stent cover may have a region in the center located between the axial tip and base ends where the filling elements are not filled in the voids. This allows endothelial cells to infiltrate from the voids in the center of the stent cover after the stent is placed in the body, so that the in-vivo object is quickly covered with endothelium, suppressing the occurrence of thrombus.

The stent cover may be in a knitted form. This allows the stent cover to exhibit excellent expandability and contractibility without tending to spread radially outward at the axial ends or to become caught by tissue in the body in the gaps.

At least a portion of the adjacent region, which is the region between the end gaps adjacent in the circumferential direction, may be filled with the filling element. As a result, the loops that are adjacent in the circumferential direction and provided at the axial end are connected by the filling element filled in the adjacent region, making it difficult for the loops to spread radially outward. This reduces the risk of end gaps located at the axial end of the stent cover getting caught on in vivo tissue, damage to the stent cover, and detachment of the stent.

All of the adjacent regions may be filled with the filling elements. This effectively prevents undesirable radial outward expansion of the axial end of the stent cover, and effectively prevents end tissues from entering the end gaps located at the axial end of the stent cover, reducing the risk of damage to the stent cover and dislodging of the stent.

The intersection region between the fibers that form loops at the axial end of the stent cover and the fibers that are aligned in the axial direction and intersect with the fibers may be filled with the filling elements. This allows the filling elements filled in the intersection region to prevent the loops at the axial end from fraying away from the fibers aligned in the axial direction. This makes it difficult for the loops to spread radially outward. This reduces the risk of end gaps at the axial end of the stent cover getting caught on in vivo tissue, damage to the stent cover, and detachment of the stent.

The filling elements may be filled into all of the end gaps. This effectively prevents undesirable radial outward expansion of the axial end of the stent cover, and effectively prevents in vivo tissue from entering the end gaps, reducing the risk of damage to the stent cover or dislodging of the stent.

The filling element filled in the end void may be continuous with the filling element filled in another void adjacent to the end void in the circumferential direction through a region radially outward and/or radially inward from the fiber. This allows adjacent filling elements to be formed continuously in the circumferential direction, suppressing undesirable radial outward expansion of the axial end of the stent cover. This further reduces the risk of end voids getting caught by in vivo tissues, etc., damaging the stent cover, or causing the stent to fall off.

The stent cover may be within the axial length of the stent. This prevents the axial end of the stent cover from undesirably spreading radially outward. This reduces the risk of end gaps getting caught on in vivo tissue, damaging the stent cover, or causing the stent to fall off.

The diameter of the filling element when it breaks may be larger than the diameter of the stent cover when it breaks. If the filling element breaks before the stent cover breaks, the stress distributed in the filling element is applied to the stent cover, so that the stent cover at the position where the filling element breaks is more likely to break than the stent cover at the position where the filling element remains. Therefore, the stent cover may break immediately after the filling element breaks. If the stent cover breaks after the filling element breaks, excessive deformation occurs in the stent cover. In contrast, if the diameter of the filling element when it breaks is larger than the diameter of the stent cover when it breaks, the stent cover breaks before the filling element breaks. Therefore, even when the stent cover breaks, the filler remains, so excessive deformation of the stent cover is prevented.

The breaking elongation of the filling element may be 300% or more. In a typical coronary artery stent placement procedure, the stent diameter before placement is 1 to 2 mm, and the stent diameter after placement is 3 to 4 mm. Therefore, if the breaking elongation of the filling element is 300% or more, the in-vivo device of the present invention can be applied in a typical coronary artery stent placement procedure without excessively deforming the stent cover.

The end of the stent cover where the filling element is filled may have a portion that overlaps radially on a cross section perpendicular to the axis in a contracted state. This ensures a large expansion diameter for the end of the stent cover even if the breaking elongation of the filling element is small. This prevents the end of the stent cover from breaking during expansion.

The stent cover may be made of a biodegradable material. This allows the stent cover to decompose and disappear after the indwelling device is placed in the body, thereby reducing the risk of a foreign body reaction originating from the stent cover.

The manufacturing method of an in vivo implant that achieves the above-mentioned object is characterized by comprising a preparation step of preparing a tubular stent that extends in the axial direction, has a tip and a base end, is formed so as to be expandable and contractible in the radial direction, has gaps, and a tubular fiber member formed in a tubular shape with fibers crossing each other to form gaps; an insertion step of inserting a core metal member into the tubular fiber member after the preparation step; a filling step of filling the gaps in the tubular fiber member with filling elements at multiple positions spaced apart in the axial direction of the tubular fiber member after the insertion step; a cutting step of cutting the tubular fiber member at an axial position of the tubular fiber member having gaps filled with the filling elements after the filling step; an attachment step of attaching the tubular composite member formed of the tubular fiber member and the filling elements obtained after the cutting step to the outer periphery of the stent; and a removal step of removing the core metal member from the tubular fiber member or the tubular composite member at any stage after the filling step and before the attachment step.

The manufacturing method for an in-vivo implant configured as described above can effectively manufacture an in-vivo implant in which at least some of the voids at the axial end of the stent cover are filled with filling elements. Furthermore, this manufacturing method prevents the generation of fiber fragments at the cut site, compared to a method in which a tubular fiber member not filled with filling elements is cut to obtain a stent cover. Therefore, by using an in-vivo implant obtained by this manufacturing method, the risk of fragments being blown into the body after placement in the body and blocking the body lumen is reduced.

The filling step may include the steps of covering the tubular fiber member with a tubular filling member formed into a tubular shape, inserting the tubular fiber member covered with the tubular filling member into a tubular heat shrinkable member, and heating the tubular heat shrinkable member at a temperature equal to or higher than the temperature at which the diameter of the tubular heat shrinkable member shrinks. Since tubular filling members have little variation between individual members, this reduces the variation in the shape of the filling elements at positions spaced apart in the axial direction.

The polymer in the tubular filling member may be oriented in the circumferential direction. This causes the filling member itself to shrink when heated, and more reliably fills the gaps in the tubular fiber member with the filling elements.

The melting point of the filling element may be lower than the melting point of the fiber. This prevents the fiber from melting due to the filling element becoming hot and melting, making it easier to maintain the structure of the stent cover.

The filling step may include a step of applying a solution containing the filling elements to the tubular fiber member and a step of drying the solution. This eliminates the need to heat the tubular fiber member to its melting point, thereby reducing the thermal load on the tubular fiber member.

The solubility of the filling elements in the solvent of the solution may be higher than the solubility of the fibers in the solvent. This prevents the fibers from dissolving, making it easier to maintain the structure of the stent cover.

FIG. 2 is a plan view showing the in-vivo indwelling device and the balloon catheter according to the embodiment. FIG. 2 is a plan view showing an in-vivo indwelling device. FIG. 1 is a plan view showing a stent. FIG. 2 is a plan view showing a portion of a stent cover. FIG. 2 is a plan view showing a portion of a stent cover. 5 is a cross-sectional view taken along line AA in FIG. 4. FIG. 1 is a diagram illustrating a first manufacturing method for an in vivo implant, in which (A) shows a state in which a protective tube and a core metal member are inserted into a tubular fiber member, (B) shows a state in which a tubular filling member is placed on the tubular fiber member, (C) shows a state in which a tubular heat-shrinkable member is placed on the tubular fiber member, (D) shows a state in which the tubular heat-shrinkable member and the tubular filling member are being heated, (E) shows a state in which the tubular heat-shrinkable member and the core metal member are being removed from the tubular fiber member, (F) shows a state in which the tubular fiber member and the tubular filling member are being cut, and (G) shows the completed stent cover and filling element after removing the protective tube. FIG. 13 is a diagram illustrating a second manufacturing method for an in vivo implantable device, in which (A) shows the state in which a protective tube and a core metal member are inserted into a tubular fiber member, (B) shows the state in which a solution is applied to the tubular fiber member, (C) shows the state in which the solvent of the solution has been evaporated, (D) shows the state in which the core metal member has been removed from the tubular fiber member, (E) shows the state in which the tubular heat-shrinkable member and the tubular filling member are being cut, and (G) shows the completed stent cover and filling element after removing the protective tube. 2 is a cross-sectional view of the in-vivo indwelling device and the balloon catheter in a contracted state taken along line BB in FIG. 1. FIG. 13 is a plan view showing a part of another example of an in-vivo indwelling device.

The following describes an embodiment of the present invention with reference to the drawings. Note that the dimensional ratios in the drawings may be exaggerated for the sake of explanation and may differ from the actual ratios.

The in-vivo device 10 according to this embodiment is used to treat lesions such as narrowed or blocked areas that occur in blood vessels, bile ducts, tracheas, esophagus, urethra, or other biological lumens. The in-vivo device 10 is mounted on a known catheter for use. As an example, the in-vivo device 10 is placed on the outer surface of the balloon 2 of a balloon catheter 1 and inserted into the biological lumen, as shown in FIG. 1.

The balloon catheter 1 has a balloon 2 at the tip of a long shaft 3 that can be expanded by fluid supplied through the inside of the shaft 3. The in-vivo device 10 is placed on the outer surface of the balloon 2 in a deflated state. The balloon 2 expands at the lesion, and together with the in-vivo device 10, it pushes open the lesion. When the balloon 2 then contracts, the in-vivo device 10 separates from the balloon 2 in an expanded state, maintaining the lesion open.

As shown in FIG. 2, the in vivo indwelling device 10 has a stent 20, a stent cover 30 that covers the stent 20, a filling element 40 that fills at least a portion of the void 32 formed in the stent cover 30, and at least one fragment 50.

As shown in FIG. 3, the stent 20 is a so-called balloon-expandable stent 20 that expands due to the expansion force of the balloon 2. The stent 20 is placed on the outer circumferential surface of the balloon 2 in a contracted state. The stent 20 is formed into a cylindrical shape as a whole by linear struts 21. The struts 21 are composed of a plurality of annular bodies 22 arranged in the axial direction of the balloon 2, and connecting elements 23 that connect adjacent annular bodies 22 in the axial direction. The shape of the stent 20 is not limited to this. The stent 20 may also be a so-called self-expandable stent 20 that expands due to the restoring force of a superelastic alloy.

Each annular body 22 is formed by folding back a number of linear elements 24 and arranging them continuously in the circumferential direction. Adjacent annular bodies 22 in the axial direction are integrally connected by a connecting element 23. Adjacent annular bodies 22 are connected by the connecting element 23 at least at one point on the circumference along the circumferential direction that intersects with the axial direction.

The width of the wire of the linear element 24 and the connecting element 23 is not particularly limited, but is, for example, 30 to 500 μm. The length of the wire of the linear element 24 and the connecting element 23 is not particularly limited, but is, for example, 0.2 to 20 mm. The thickness of the wire of the linear element 24 and the connecting element 23 is not particularly limited, but is, for example, 30 to 500 μm. The outer diameter of the stent 20 when expanded is approximately the same as the inner diameter of the stent cover 30 when expanded, but may be larger or smaller. The axial length of the stent 20 when expanded is approximately the same as the axial length of the stent cover 30 when expanded, but may be longer or shorter.

The stent 20 is placed on the outer surface of the deflated balloon 2 in a radially contracted state. When the balloon 2 expands, the angle between the circumferentially adjacent linear elements 24 widens, and the stent 20 expands radially.

The stent 20 can be made of any known material, such as metal materials such as stainless steel, cobalt-chromium alloy, and nickel-titanium alloy, or polymer materials such as polylactic acid and polycaprolactone.

As shown in Figs. 2, 4 to 6, the stent cover 30 is formed in a tubular knit form using flexible fibers 31. The stent cover 30 is formed in a tubular form with multiple voids 32 so as to cover the stent 20. The stent cover 30 has a central portion 33 between the axial tip and base end. In the stent cover 30, the flexible fibers 31 are alternately folded back to form multiple loops 34. The loops 34 are defined as fibers 31 divided by the length from a folded portion on one end side in the axial direction to another folded portion on the one end side via a folded portion on the other end side. Note that the orientation of the one end side and the orientation of the other end side are not fixed, and may be set each time. The voids 32 are defined as the area inside the loops 34. The multiple loops 34 are arranged continuously in the circumferential direction and arranged in a spiral. The original loops 34 and the loops 34 formed at the same circumferential position after an arbitrary number of loops 34 are arranged in succession are crossed while being shifted in the axial direction. Because the fibers 31 are continuous in this way, the knit has a tubular structure with loops 34 connected in the circumferential and axial directions. The multiple loops 34 connected in the circumferential direction form different rows 38 every 360 degrees.

As shown in FIG. 5, the stent cover 30 has multiple end gaps 35, multiple adjacent regions 36, and multiple intersection regions 37 at each axial end. The end gaps 35 are gaps 32 located at the axial end and formed by loops 34 that are convex toward the end, and are the inner regions of the loops 34 that extend from the folded portion 34B on the central portion 33 side to the other folded portion 34B on the central portion 33 side via the folded portion 34A on the end side.

The adjacent region 36 is a gap 32 located between two end gaps 35 adjacent in the circumferential direction. In other words, the adjacent region 36 is an inner region of the loop 34 that is convex toward the central portion 33 and is divided by the length from the folded portion 34A on the end side through the folded portion 34B on the central portion 33 side to the other folded portion 34A on the end side. At each end of the stent cover 30, the end gaps 35 and the adjacent region 36 are alternately arranged in the circumferential direction.

The intersecting region 37 is a region surrounded by the fiber 31 that is located at the axial end of the stent cover 30 and forms a loop 34, and the fiber 31 that intersects with the fiber 31 in the center 33, and is also part of the adjacent region 36.

The fiber diameter is not particularly limited, but is, for example, 0.007 to 0.1 mm, and preferably 0.01 to 0.03 mm. The outer diameter of the stent cover 30 when expanded is not particularly limited, but is, for example, 1.00 to 50.00 mm, and preferably 2.25 to 4.00 mm. The axial length of the stent cover 30 is not particularly limited, but is, for example, 5 to 250 mm, and preferably 12 to 38 mm.

The wale width W, which is the distance between the rows 38 aligned in the axial direction when expanded, i.e., the length by which the circumferentially extending fibers 31 are displaced in the axial direction for each revolution, is not particularly limited, but is, for example, 0.015 to 8.0 mm, and preferably 0.15 to 0.95 mm. The course width C, which is the distance between the loops 34 aligned in the circumferential direction when expanded, is not particularly limited, but is, for example, 0.01 to 5.0 mm, and preferably 0.1 to 0.6 mm.

The material of the fibers 31 forming the stent cover 30 is not particularly limited, but biodegradable or non-biodegradable materials can be used. Biodegradable materials include, for example, polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polydioxanone (PDO), trimethylene carbonate (PTMC), or copolymers thereof (binary copolymers, ternary copolymers, and quaternary copolymers), such as glycolic acid-lactic acid copolymers (PGA-LA) and glycolic acid-caprolactone copolymers (PGA-CL). Among these, polyglycolic acid, glycolic acid-lactic acid copolymers, and glycolic acid-caprolactone copolymers are particularly preferred, and polyglycolic acid is more preferred. The breaking elongation of polyglycolic acid is about 40%. Non-biodegradable materials include, for example, polyethylene terephthalate (PET), polyolefin (PO), acrylic oxide, polytetrafluoroethylene (PTFE), polyethylene covinyl acetate (PEVA), polyethylene elastomers, polyethylene oxide polybutylene terephthalate copolymers (PEO-PBT), polyethylene oxide polylactic acid copolymers (PEO-PLA), polybutyl methacrylate (PBMA), polyurethane (PU), silicone-polycarbonate urethane copolymers (SPCU), medical grade polycarbonate urethane (PCU), polyamide (PA), polyether ether ketone (PEEK), polyacrylic acid (PAA), polymethacrylic acid (PMA), carboxylic acid moieties including one or more of maleic acid, helical acid, taconic acid, and/or monomers thereof, thermoplastic polymers, thermosetting polymers, polyolefin elastomers, polyesters, polyurethanes, polyfluoropolymers, and/or polyamide combinations and/or esters, etc.

The fragments 50 are small pieces cut and separated from the fibers 31, and are placed at each axial end of the in-vivo implant 10. The fragments 50 are formed by cutting the loops 34 when cutting out a stent cover 30 having a predetermined axial length from a long tubular woven fiber member 60 (see FIG. 7). The fragments 50 are hooked onto the loops 34 that form the end gaps 35, but they do not have to be hooked. The in-vivo implant 10 does not have to have the fragments 50.

The filling element 40 is filled into one or more end voids 35 at at least one axial end of the stent cover 30. In this embodiment, the filling element 40 is filled into all end voids 35 located at both axial ends of the stent cover 30. The filling element 40 may fill only a portion of each end void 35, or may fill each end void 35 entirely. For example, in a development view of the stent cover 30 seen from the radial outside, an area of about 10% of the area of one end void 35 may be filled with the filling element 40.

The filling elements 40 may be filled only in the end gaps 35 of the rows 38 located at each end of the stent cover 30 in the axial direction, or may be filled in the gaps 32 across multiple rows 38 from the end toward the central portion 33. When the filling elements 40 are filled in this way, in cases where the loops 34 of the rows 38 on the central portion 33 side spread radially outward as the loops 34 of the end spread radially outward, the infiltration of in vivo tissues and the like into the gaps 32 on the central portion 33 side from the end is suppressed, and the risk of damage to the stent cover 30 and detachment of the stent 20 is reduced.

The filling elements 40 are filled in one or more adjacent regions 36 at one or both axial ends of the stent cover 30. The filling elements 40 may fill only a portion of each adjacent region 36, or may fill the entire adjacent region 36. For example, in a development view of the stent cover 30 seen from the radial outside, an area of about 10% of the area of one adjacent region 36 may be filled with the filling elements 40.

The filling elements 40 are filled in one or more intersection regions 37 at one or both axial ends of the stent cover 30. The filling elements 40 may fill only a portion of each intersection region 37, or may fill each intersection region 37 entirely. For example, in a development view of the stent cover 30 seen from the radial outside, about 10% of the area of one intersection region 37 may be filled with the filling elements 40.

In this embodiment, the filling elements 40 fill all of the voids 32 located within a predetermined length range from both axial ends of the stent cover 30 toward the central portion 33. The stent cover 30 has voids 32 in the central portion 33 that are not filled with the filling elements 40.

As shown in FIG. 6, the filling element 40 filled in the end void 35 is continuous with the filling element 40 filled in the other void 32 adjacent to the end void 35 (the adjacent region 36 in this embodiment) through a region radially outward and/or radially inward from the fiber 31. The filling element 40 filled in the end void 35 may not be continuous with the filling element 40 filled in the other void 32 adjacent to the end void 35 through a region radially outward and/or radially inward from the fiber 31. The thickness of the filling element 40 filled in the end void 35 may be equal to or greater than the diameter of the fiber 31, or may be equal to or less than the diameter of the fiber 31. The shortest distance t1 from the outer surface of the filling element 40 filled in the void 32 to the fiber 31 is preferably equal to or less than the fiber diameter. The smaller the shortest distance t1, the more the increase in the outer diameter of the in-vivo indwelling device 10 is suppressed, and the peripheral reachability of the in-vivo indwelling device 10 is improved. The minimum distance t1 is preferably 0 to 0.5 mm, and more preferably 0 to 0.03 mm.

The shortest distance t2 from the inner surface of the filling element 40 filling the gap 32 to the fiber 31 is preferably equal to or less than the fiber diameter. The smaller the shortest distance t2, the larger the internal lumen area of the indwelling device 10, and therefore the greater the blood flow supply from the indwelling device 10 to the periphery. The shortest distance t2 is preferably 0 to 0.5 mm, and more preferably 0 to 0.03 mm.

In this embodiment, the fragment 50 is included and fixed within the filling element 40, but it does not have to be included within the filling element 40. The fragment 50 has the effect of making the end of the stent cover 30 less likely to deform. In addition, other reinforcing elements may be included within the filling element 40 instead of or in addition to the fragment 50.

The material of the filling element 40 is not particularly limited, but biodegradable or non-biodegradable materials can be used. Examples of biodegradable materials include polyglycolic acid (PGA), polylactic acid (PLA), polycaprolactone (PCL), polydioxanone (PDO), trimethylene carbonate (PTMC), or copolymers thereof (binary copolymers, ternary copolymers, and quaternary copolymers), such as lactic acid-caprolactone copolymers (PLA-CL). Among these, polycaprolactone and lactic acid-caprolactone copolymers are particularly preferred, and PDLLA-CL, which is one of the lactic acid-caprolactone copolymers, is more preferred. The breaking elongation of PDLLA-CL is approximately 1000%. Among the biodegradable materials mentioned above, the material with the highest breaking elongation is polycaprolactone, which has a breaking elongation of 1500%.

Non-biodegradable materials include, for example, polyolefins (PO), acrylic oxide, polytetrafluoroethylene (PTFE), polyethylene covinyl acetate (PEVA), polyethylene elastomers, polyethylene oxide polybutylene terephthalate copolymers (PEO-PBT), polyethylene oxide polylactic acid copolymers (PEO-PLA), polybutyl methacrylate (PBMA), polyurethanes (PU), silicone-polycarbonate urethane copolymers (SPCU), medical grade polycarbonate urethane (PCU), polyamides (PA), polyether ether ketones (PEEK), polyacrylic acids (PAA), polymethacrylic acids (PMA), carboxylic acid moieties including one or more of maleic acid, helical acid, taconic acid, and/or monomers thereof, thermoplastic polymers, thermosetting polymers, polyolefin elastomers, polyesters, polyurethanes, polyfluoropolymers, and/or combinations and/or esters of polyamides (PA), and the like.

The material of the filling element 40 may be, for example, placed on the stent cover 30 in a melted state and then cooled to harden, or may be placed on the stent cover 30 in a dissolved state in a solvent and then the solvent is dried to harden. Therefore, when the material of the filling element 40 is melted, it is preferable that the material of the stent cover 30 has a lower melting point than the material of the stent cover 30 so that the stent cover 30 is not melted. Also, when the filling element 40 is dissolved in a specific solvent, it is preferable that the material of the stent cover 30 is insoluble or difficult to dissolve in that solvent.

The material of the filling element 40 is preferably biodegradable and has better elasticity than the material of the stent cover 30.

The stent cover 30 and the stent 20, with the end gaps 35 filled with the filling elements 40, may be fixed in whole or in part by known techniques such as gluing, fusing, or tying with thread. Fixing the stent cover 30 and the stent 20 reduces the risk that the stent cover 30 will fall off the stent 20 during delivery.

Next, the operation of the in-vivo indwelling device 10 according to this embodiment will be described.
In the in-vivo indwelling device 10, the end gaps 35, adjacent regions 36, and intersection regions 37 at both axial ends of the stent cover 30 are filled with the filling elements 40. This prevents the end of the axial direction of the stent cover 30 from spreading outward in the radial direction and the fibers 31 from fraying. This prevents tissue in the body from getting caught in the end gaps 35 during delivery of the balloon catheter 1, thereby preventing damage to the stent cover 30 and the detachment of the stent 20. Furthermore, by preventing the spread of the stent cover 30 and the fraying and breakage of the fibers 31, the therapeutic effect is maintained high without being reduced, and the occurrence of stent thrombosis due to disturbance of blood flow is prevented.

<First manufacturing method>
Next, a first method for manufacturing the in-vivo implant 10 will be described with reference to Fig. 7. In this method, the material of the filling element 40 is filled into the gap 32 of the stent cover 30 in a molten state.

First, a tubular stent 20 and a tubular fiber member 60 formed by knitting fibers 31 to have voids 32 are prepared (preparation step). Next, as shown in FIG. 7(A), a stainless steel core member 100 covered with a protective tube 101 made of PTFE, for example, is inserted into the lumen of the tubular fiber member 60 (insertion step). Since the protective tube 101 is made of PTFE, it prevents the molten material from adhering to the core member 100. The material of the protective tube 101 is not limited to PTFE as long as the molten material is not easily adhered to the material. The protective tube 101 does not have to be provided. The material of the core member 100 is not limited to stainless steel. The axial length of the tubular fiber member 60 is set to a length that allows multiple stent covers 30 to be cut out.

Next, as shown in FIG. 7(B), tubular filling members 110 formed into a tubular shape from the material of the filling element 40 are placed on the tubular fiber member 60 at multiple positions spaced apart in the axial direction. The inner diameter of the tubular filling member 110 is approximately equal to the outer diameter of the tubular fiber member 60. The axial length of the tubular filling member 110 is approximately twice the axial length of the filling element 40 that is ultimately formed.

Next, as shown in FIG. 7(C), the outside of the tubular fiber member 60 and the tubular filling member 110 are covered with a tubular heat-shrinkable member 120. The tubular heat-shrinkable member 120 is a so-called heat-shrinkable tube that shrinks in diameter when heated.

Ideally, the material of the tubular heat shrink member 120 is a material that exhibits shrinkage capability in a temperature range from the melting point of the filling element to a temperature range at which the stent cover 30 does not deform. The material of the tubular heat shrink member 120 is, for example, polyolefin (PO), fluoropolymer (fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), etc.), polyvinyl chloride (PVC), chloroprene rubber, silicone elastomer, etc., and is preferably polyolefin.

7(D), the tubular fiber member 60, the tubular filling member 110, and the tubular heat shrinkable member 120 are heated by a known heating means such as an oven. At this time, it is preferable to heat the tubular fiber member 60, the tubular filling member 110, and the tubular heat shrinkable member 120 uniformly without bias in the axial and circumferential directions. The heating temperature is below the melting point of the fiber 31 constituting the tubular fiber member 60, above the shrinkage temperature of the tubular heat shrinkable member 120, and above the melting point of the tubular filling member 110. As a result, the fiber 31 does not melt due to heating, the tubular heat shrinkable member 120 shrinks in diameter, and the tubular filling member 110 melts. Therefore, the melted tubular filling member 110 is pressed by the shrinking tubular heat shrinkable member 120 to fill the gaps 32 of the fiber 31 of the tubular fiber member 60 (filling process). At this time, the protective tube 101 prevents the melted tubular filling member 110 from adhering to the core metal member 100. The tubular filling member 110 may be oriented in the circumferential direction in advance by blow molding or the like. This allows the tubular filling member 110 to shrink in diameter not only by being pressed by the tubular heat-shrinkable member 120 but also by its own shrinking effect, allowing for a more uniform shrinkage. Therefore, the tubular filling member 110 shrinks in diameter uniformly, melts in close contact with the tubular fiber member 60, and is well filled into the gaps 32 of the tubular fiber member 60.

Next, as shown in FIG. 7(E), the tubular fiber member 60 and the tubular heat-shrinkable member 120 are cooled. This causes the tubular filling member 110 to harden and form the filling element 40. After this, the tubular heat-shrinkable member 120 is removed, and the core metal member 100 is pulled out from the tubular fiber member 60 (removal process). At this time, since the protective tube 101 is provided between the tubular fiber member 60 and the core metal member 100, it is easy to pull out the core metal member 100 from the tubular fiber member 60.

Next, as shown in FIG. 7(F), the tubular fiber member 60 is cut together with the protective tube 101 at an axial position of the tubular fiber member 60 having the voids 32 filled with the filling elements 40 (cutting step). The cutting position is approximately the center of the axial direction of each filling element 40. As a result, both sides of the cut site form axial end portions of different stent covers 30 in which the voids 32 are filled with the filling elements 40. Note that the step of removing the core metal member 100 from the tubular fiber member 60 may be performed after cutting the tubular fiber member 60 and the filling elements 40. In this case, the tubular fiber member 60 and the filling elements 40 are cut together with the core metal member 100.

Next, as shown in FIG. 7(G), the protective tube 101 is removed from the tubular composite member 70 formed from the cut tubular fiber member 60 and the filling element 40. The protective tube 101 may be removed from the tubular fiber member 60 together with the core metal member 100 or after the core metal member 100 is removed in the removal process. After this, the tubular composite member 70 is attached by covering the outer periphery of the stent 20 (attachment process). In this way, the in vivo indwelling device 10 having the stent 20, the stent cover 30, and the filling element 40 is completed. In this method, the filling element 40 is filled into the gap 32 of the tubular fiber member 60, and then the portion filled with the filling element 40 is cut, so that fraying of the fiber 31 is prevented, and the fragments 50 formed by cutting are held within the filling element 40 and do not fall off. Therefore, the risk of the fragments 50 scattering to the periphery of the biological lumen and blocking the peripheral lumen is suppressed.

After cutting the tubular fiber member 60 to form the stent cover 30, the tubular filling member 110 may be placed at the axial end of the stent cover 30, and the filling element 40 may be filled into the end gap 35 by the tubular heat shrink member 120.

As Example 1, an in-vivo indwelling device 10 was produced by the above-mentioned first production method.
The prepared tubular fiber member 60 had an outer diameter of 4.0 mm and an axial length of about 500 mm. The material of the tubular fiber member 60 was PET, and the material of the filling element 40 was LCL5050. LCL5050 is a polymer with better elongation than PET and a lower melting point.

Next, a stainless steel core member 100 covered with a PTFE protective tube 101 was inserted into the lumen of the tubular fiber member 60. Next, the tubular fiber member 60 was covered with a plurality of tubular filling members 110, and further covered with a tubular heat-shrinkable member 120. After this, it was heated using an oven. The heating temperature was about 150°C. After this, the core member 100 was removed from the cooled tubular fiber member 60, and the part of the tubular fiber member 60 filled with the filling elements 40 was cut together with the protective tube 101. After this, the protective tube 101 was removed from the cut tubular fiber member 60, and a tubular composite member 70 having a stent cover 30 and the filling elements 40 filled in the voids 32 of the stent cover 30 was obtained. The outer diameter of the stent cover 30 of the obtained tubular composite member 70 was 2.7 mm. Next, a tubular composite member 70 was placed over the outer circumference of the prepared stent 20, which had an outer diameter of 2.0 mm and was expandable to 4.5 mm or more, to obtain an in-vivo indwelling device 10.

The in-vivo indwelling device 10 according to Example 1 obtained was placed on the outer periphery of a balloon 2 expandable to 4.2 mm or more, and the balloon 2 was expanded until the outer diameter became 4.0 mm. As a result, the outer diameter of the stent cover 30 expanded to 4.2 mm. The balloon 2 was then deflated and removed from the in-vivo indwelling device 10. As a result, the outer diameter of the stent cover 30 became 4.1 mm. During the expansion, no breakage of the filling element 40, fraying of the fiber 31, or falling off of the fragments 50 was observed.

<Second manufacturing method>
Next, a second method for producing the in-vivo indwelling device 10 will be described with reference to Fig. 8. In this method, the material of the filling element 40 is filled into the gap 32 of the stent cover 30 in a state of being dissolved in a solvent.

First, a tubular stent 20 and a tubular fiber member 60 formed by knitting fibers 31 into a tubular shape so as to have voids 32 are prepared (preparation step). Next, as shown in FIG. 8(A), a core metal member 100 covered with a protective tube 101 is inserted into the lumen of the tubular fiber member 60 (insertion step). The preparation step and insertion step are the same as those in the first manufacturing method described above.

8B, the tubular fiber member 60 is impregnated at a plurality of positions spaced apart in the axial direction with a solution 130 in which the material of the filling element 40 is dissolved in a solvent. Methods for supplying the solution 130 to the desired positions include, for example, dispense coating using a tube 131, spray coating in which the solution 130 is sprayed, and dipping coating in which only the axial end of the tubular fiber member 60 cut to a predetermined length is immersed in the solution 130. In the spray coating, it is preferable to mask the tubular fiber member 60 in the range in which the filling element 40 is not formed. A solvent that does not affect the material of the stent cover 30 (tubular fiber member 60) is selected. The axial length of each range of the tubular fiber member 60 impregnated with the solution 130 is approximately twice the axial length of the filling element 40 to be finally formed. The protective tube 101 prevents the solution 130 from adhering to the core metal member 100.

The solvent is not particularly limited as long as the filling element 40 is soluble in the solvent. The solvent may be ethanol, acetone, tetrahydrofuran, dimethylformamide, dimethylsulfoxide, chloroform, dichloromethane, hexane, ether, or the like, and is preferably acetone or chloroform.

Next, the solvent contained in the solution 130 impregnated in the tubular fiber member 60 is volatilized by heating or reducing the pressure. As a result, the gaps 32 in the fibers 31 of the tubular fiber member 60 are filled with the filling elements 40 (filling process), as shown in FIG. 8(C).

Next, as shown in FIG. 8(D), the core metal member 100 is removed from the tubular fiber member 60 (removal process). At this time, since the protective tube 101 is provided between the tubular fiber member 60 and the core metal member 100, it is easy to pull out the core metal member 100 from the tubular fiber member 60.

Next, as shown in FIG. 8(E), the tubular fiber member 60 is cut together with the protective tube 101 at an axial position of the tubular fiber member 60 having the voids 32 filled with the filling elements 40 (cutting process). The cutting position is approximately the center in the axial direction of the range in which each filling element 40 is filled.

Next, as shown in FIG. 8(F), the protective tube 101 is removed from the tubular composite member 70 formed from the cut tubular fiber member 60 and the filling element 40. The protective tube 101 may be removed from the tubular fiber member 60 together with the core metal member 100 in the removal process, or after the core metal member 100 is removed. After this, the tubular composite member 70 is attached by covering the outer periphery of the stent 20 (attachment process). This completes the in-vivo indwelling device 10 having the stent 20, stent cover 30, and filling element 40. The steps after the cutting process are the same as those in the first manufacturing method described above.

As Example 2, the in-vivo indwelling device 10 was produced by the above-mentioned second production method.
The prepared tubular fiber member 60 had an outer diameter of 4.0 mm and an axial length of about 500 mm. The material of the tubular fiber member 60 was PGA, and the material of the filling element 40 was DLCL9010. The solvent was acetone. DLCL9010 is a polymer that is more extensible than PGA and easily dissolves in acetone.

Next, a stainless steel core member 100 covered with a PTFE protective tube 101 was inserted into the lumen of the tubular fiber member 60. Next, a solution 130 was prepared by dissolving DLCL9010, the material of the filling element 40, in acetone, the solvent, and impregnated into multiple positions in the axial direction of the tubular fiber member 60 by dispense coating. After that, the solution was heated under reduced pressure to volatilize the solvent. The heating temperature was about 60°C. After that, the core member 100 was removed from the cooled tubular fiber member 60, and the portion of the tubular fiber member 60 filled with the filling element 40 was cut together with the protective tube 101. After that, the protective tube 101 was removed from the cut tubular fiber member 60, and a tubular composite member 70 having a stent cover 30 and the filling element 40 filled in the gap 32 of the stent cover 30 was obtained. The outer diameter of the stent cover 30 of the obtained tubular composite member 70 was 2.3 mm. Next, the in-vivo indwelling device 10, in which the tubular composite member 70 was placed on the outer periphery of the prepared stent 20 having an outer diameter of 2.0 mm and expandable to 4.5 mm or more, was crimped on the outer surface of the balloon 2 using a known crimping machine. The outer diameter of the stent cover 30 after crimping was 1.38 mm in the area filled with the filling elements 40 at the axial end, and 1.55 mm in the central part 33 where the filling elements 40 were not filled. In the stent cover 30 contracted by crimping, a plurality of folded parts 39 protruding radially outward were formed in a circumferential line in the area filled with the filling elements 40 at the axial end of the stent cover 30, as shown in FIG. 9. In the folded parts 39, the stent cover 30 overlaps radially on a cross section perpendicular to the axis.

The in-vivo indwelling device 10 according to Example 2 obtained was placed on the outer periphery of a balloon 2 that can be expanded to 3.7 mm or more, and the balloon 2 was expanded until the outer diameter became 3.5 mm. The balloon 2 was then deflated and removed from the in-vivo indwelling device 10. As a result, the outer diameter of the stent cover 30 became 3.7 mm. During the expansion, no breakage of the filling element 40, fraying of the fiber 31, or falling off of the fragments 50 was observed.

As described above, the in-vivo implant device 10 according to this embodiment includes a tubular stent 20 that extends in the axial direction, has a tip and a base end, is formed to be capable of radial expansion and contraction, and has gaps; a tubular stent cover 30 that extends in the axial direction, has a tip and a base end, is formed to be capable of radial expansion and contraction, has voids 32, and is formed of fibers 31; and a filling element 40 that fills at least a portion of the voids 32 in the stent cover 30. The voids 32 in the stent cover 30 are areas surrounded by the fibers 31 and are arranged continuously in the circumferential and axial directions over the entire circumference and length. The voids 32 located at the axial end of the stent cover 30 and arranged in the circumferential direction are defined as end voids 35, and the filling element 40 fills at least a portion of the end voids 35.

The in-vivo implant device 10 configured as described above has the filling element 40 filled in at least a portion of the end gap 35 at the axial end of the stent cover 30, which prevents the axial end of the stent cover 30 from undesirably spreading radially outward and prevents in-vivo tissue and the like from entering the end gap 35, thereby reducing the risk of damage to the stent cover 30 and of the stent 20 falling off.

The stent cover 30 also has an area in the central portion 33 located between the axial tip and base ends where the filling elements 40 are not filled in the voids 32. As a result, after the stent 20 is placed in the body, endothelial cells infiltrate from the voids 32 in the central portion 33 of the stent cover 30, so that the in-vivo device 10 is covered with endothelium early on, and the occurrence of thrombus is suppressed.

The stent cover 30 is also in a knitted form. This allows the stent cover 30 to exhibit excellent expandability and contractibility without tending to spread radially outward at the axial ends, and without tending to cause the gaps 32 to catch on tissue in the body.

In addition, at least a portion of the adjacent region 36, which is the region between circumferentially adjacent end gaps 35, is filled with the filling elements 40. As a result, the loops 34 that are provided at the axial ends and adjacent in the circumferential direction are connected by the filling elements 40 filled in the adjacent region 36, making it difficult for the loops 34 to spread radially outward. This reduces the risk of end gaps 35 located at the axial ends of the stent cover 30 getting caught on in vivo tissue, damage to the stent cover 30, and detachment of the stent 20.

In addition, all adjacent regions 36 are filled with filling elements 40. This effectively prevents undesirable radial outward expansion of the axial end of the stent cover 30, and effectively prevents end tissues from entering the end gaps 35 located at the axial end of the stent cover 30, reducing the risk of damage to the stent cover 30 and of the stent 20 falling off.

In addition, the intersection region 37 between the fiber 31 that is located at the axial end of the stent cover 30 and forms the loop 34 and the fiber 31 that is aligned in the axial direction and intersects with the fiber 31 is filled with the filling element 40. As a result, the filling element 40 filled in the intersection region 37 prevents the loop 34 located at the axial end from fraying out of the fiber 31 aligned in the axial direction. This makes it difficult for the loop 34 to spread radially outward. This reduces the risk of the end gap 35 located at the axial end of the stent cover 30 getting caught on in vivo tissue, damage to the stent cover 30, and detachment of the stent 20.

The filling elements 40 are also filled into all end gaps 35. This effectively prevents undesirable radial outward expansion of the axial end of the stent cover 30, and effectively prevents in vivo tissue from entering the end gaps 35, reducing the risk of damage to the stent cover 30 and the detachment of the stent 20.

The filling elements 40 filled in the end voids 35 are continuous with the filling elements 40 filled in other voids 32 circumferentially adjacent to the end voids 35 through the region radially outward and/or radially inward from the fibers 31. As a result, the filling elements 40 adjacent to each other in the circumferential direction are formed continuously, suppressing undesirable radial outward expansion of the axial end of the stent cover 30. This further reduces the risk of end voids 35 getting caught by in vivo tissues, damage to the stent cover 30, or detachment of the stent 20.

The stent cover 30 is within the axial length of the stent 20. This prevents the axial end of the stent cover 30 from undesirably spreading radially outward. This reduces the risk of end gap 35 catching on tissue in the body, damaging the stent cover 30, or causing the stent 20 to fall off. The axial length of the stent cover 30 may be the same as the axial length of the stent 20, or may be slightly longer than the axial length of the stent 20.

In addition, the diameter at which the filling element 40 breaks is larger than the diameter at which the stent cover 30 breaks. If the filling element 40 breaks before the stent cover 30 breaks, the stress distributed in the filling element 40 is applied to the stent cover 30, so that the stent cover 30 at the position where the filling element 40 breaks is more likely to break than the stent cover 30 at the position where the filling element 40 remains. For this reason, the breakage of the stent cover 30 can occur immediately after the breakage of the filling element 40. If the stent cover 30 breaks after the breakage of the filling element 40, excessive deformation occurs in the stent cover 30. In contrast, if the diameter at which the filling element 40 breaks is larger than the diameter at which the stent cover 30 breaks, the breakage of the stent cover 30 occurs before the breakage of the filling element 40. Therefore, even when the stent cover 30 breaks, the filler remains, so excessive deformation of the stent cover 30 is prevented. For this reason, it is preferable that the diameter at which the filling element 40 breaks is larger than the diameter at which the stent cover 30 breaks. It is more preferable that the filling element 40 does not break until it reaches the desired expanded diameter.

The breaking elongation of the filling element 40 is preferably 300% or more. In a typical coronary stent placement procedure, the outer diameter of the stent before placement is 1 to 2 mm, and the outer diameter of the stent after placement is 3 to 4 mm. Therefore, if the breaking elongation of the filling element 40 is 300% or more, the in-vivo indwelling device 10 of the present invention can be applied in a typical coronary stent placement procedure without excessively deforming the stent cover 30.

In addition, the end of the stent cover 30 where the filling element 40 is filled has a portion that overlaps radially on a cross section perpendicular to the axis in the contracted state. This ensures that the expansion diameter of the end of the stent cover 30 is large even if the breaking elongation of the filling element 40 is small. This prevents the end of the stent cover 30 from breaking during expansion.

The stent cover 30 is preferably made of a biodegradable material. This allows the stent cover 30 to decompose and disappear after the indwelling device 10 is placed in the body, thereby reducing the risk of a foreign body reaction originating from the stent cover 30.

The manufacturing method of the in vivo indwelling device 10 according to this embodiment includes a preparation step of preparing a tubular stent 20 that extends in the axial direction, has a tip and a base end, is formed so as to be expandable and contractible in the radial direction, and has gaps, and a tubular fiber member 60 formed in a tubular shape in which fibers 31 cross to have voids 32; an insertion step of inserting a core metal member 100 into the tubular fiber member 60 after the preparation step; and an insertion step of inserting a filling element 100 into the voids 32 of the tubular fiber member 60 at multiple positions spaced apart in the axial direction of the tubular fiber member 60 after the insertion step. The method includes a filling step of filling the tubular fiber member 60 with the filling elements 40, a cutting step of cutting the tubular fiber member 60 at an axial position of the tubular fiber member 60 having the voids 32 filled with the filling elements 40 after the filling step, an attachment step of attaching the tubular fiber member 60 obtained after the cutting step and the tubular composite member 70 formed by the filling elements 40 to the outer periphery of the stent 20, and a removal step of removing the core metal member 100 from the tubular fiber member 60 or the tubular composite member 70 at any stage after the filling step and before the attachment step.

The manufacturing method of the in-vivo device 10 configured as described above can effectively manufacture an in-vivo device 10 in which at least some of the gaps 32 at the axial end of the stent cover 30 are filled with the filling elements 40. This manufacturing method prevents the generation of fragments 50 of the fibers 31 at the cut site, compared to a method in which a tubular fiber member 60 not filled with filling elements is cut to obtain a stent cover 30. Therefore, by using the in-vivo device 10 obtained by this manufacturing method, the risk of fragments 50 being blown into the body and blocking the body lumen after placement in the body is reduced.

The filling step may also include the steps of covering the tubular fiber member 60 with a tubular filling member 110 formed into a tubular shape, inserting the tubular fiber member 60 covered with the tubular filling member 110 into a tubular heat-shrinkable member 120, and heating the tubular fiber member 60 at a temperature equal to or higher than the temperature at which the tubular heat-shrinkable member 120 shrinks in diameter. Since the tubular filling member 110 has little variation between individual members, this reduces the variation in the shape of the filling elements 40 at positions spaced apart in the axial direction.

The polymers in the tubular filling member 110 may be oriented in the circumferential direction. This causes the filling member itself to shrink when heated, and more reliably fills the gaps 32 in the tubular fiber member 60 with the filling elements 40.

The melting point of the filling element 40 is lower than that of the fiber 31. This prevents the fiber 31 from melting due to the high temperature of the filling element 40, making it easier to maintain the structure of the stent cover 30.

The filling process may also include a step of applying a solution 130 containing the filling elements 40 to the tubular fiber member 60 and a step of drying the solution 130. This eliminates the need to heat the filling elements 40 to their melting point, thereby reducing the thermal load on the tubular fiber member 60.

The solubility of the filling elements 40 in the solvent of the solution 130 may be higher than the solubility of the fibers 31 in the solvent. This prevents the fibers 31 from dissolving, making it easier to maintain the structure of the stent cover 30.

The present invention is not limited to the above-mentioned embodiment, and various modifications can be made by those skilled in the art within the technical concept of the present invention. For example, as shown in another example in FIG. 10, the stent cover 30 may be in the form of a woven fabric formed by intersecting a plurality of weft fibers 31A and a plurality of warp fibers 31B. In this case, at the end of the stent cover 30, end gaps 35 surrounded on both sides in the axial direction and both sides in the circumferential direction by fibers 31 are arranged in the circumferential direction. In addition, no adjacent region 36 is provided. The fiber spacing of the weft fibers 31A and the fiber spacing of the warp fibers 31B are not particularly limited, but are preferably 0.01 to 8.0 mm, and more preferably 0.1 to 0.95 mm. In addition, other dimensions of the stent cover 30 can be the same as those of the above-mentioned embodiment.

In addition, known drugs such as immunosuppressants may be included on or inside the stent 20, stent cover 30, or filling element 40.

REFERENCE SIGNS LIST 10 In-vivo indwelling device 20 Stent 30 Stent cover 31 Fiber 31A Weft fiber 31B Warp fiber 32 Void 33 Central portion 34 Loop 35 End void 36 Adjacent region 37 Intersecting region 38 Row 39 Folded portion 40 Filling element 50 Fragment 60 Tubular fiber member 70 Tubular composite member 100 Core metal member 101 Protective tube 110 Tubular filling member 120 Tubular heat-shrinkable member 130 Solution

Claims (19)

a tubular stent extending in an axial direction, having a distal end and a proximal end, configured to be radially expandable and contractible, and having a gap;
a stent cover that is axially extending, has a distal end and a proximal end, is formed so as to be capable of radial expansion and contraction, has a tubular shape with a void, and is formed of a fiber;
and a filling element for filling at least a part of the void of the stent cover,
The voids of the stent cover are areas surrounded by the fibers, and are arranged continuously in a circumferential direction and an axial direction over the entire circumference and length of the stent cover,
The voids located at the axial end of the stent cover and arranged in the circumferential direction are defined as end voids,
The filling element is filled in at least a part of the end gap. The in-vivo indwelling device according to claim 1, wherein the stent cover has a region in the central portion located between the axial tip and base ends where the filling element is not filled in the gap. The in-vivo indwelling device according to claim 1 or 2, characterized in that the stent cover is in a knitted form. The in-vivo indwelling device according to claim 3, characterized in that at least a portion of the adjacent regions, which are regions between the end gaps adjacent in the circumferential direction, is filled with the filling element. The in-vivo indwelling device according to claim 4, characterized in that all of the adjacent regions are filled with the filling element. The in-vivo indwelling device according to any one of claims 3 to 5, characterized in that the intersecting region, which is the region between the fiber located at the axial end of the stent cover and forming a loop, and the fiber that intersects with the fiber in the axial direction, is filled with the filling element. The in-vivo indwelling device according to any one of claims 1 to 6, characterized in that the filling element is filled in all of the end gaps. The in-vivo indwelling device according to any one of claims 1 to 7, characterized in that the filling element filled in the end void is continuous with the filling element filled in another void adjacent to the end void in the circumferential direction via a region radially outward and/or radially inward from the fiber. The in-vivo indwelling device according to any one of claims 1 to 8, characterized in that the stent cover is within the range of the axial length of the stent. The in-vivo indwelling device according to any one of claims 1 to 9, characterized in that the diameter of the filling element when it breaks is larger than the diameter of the stent cover when it breaks. The in-vivo indwelling device according to any one of claims 1 to 10, characterized in that the breaking elongation of the filling element is 300% or more. The in-vivo indwelling device according to any one of claims 1 to 11, characterized in that the end of the stent cover into which the filling element is filled has a portion that overlaps radially on a cross section perpendicular to the axis in a contracted state. The in-vivo indwelling device according to any one of claims 1 to 12, characterized in that the stent cover is made of a biodegradable material. a preparation step of preparing a tubular stent having gaps, which extends in an axial direction, has a tip end and a base end, is formed so as to be capable of expanding and contracting in a radial direction, and a tubular fiber member formed in a tubular shape in which fibers cross to have voids;
an inserting step of inserting a core metal member into the tubular fiber member after the preparing step;
a filling step of filling the voids of the tubular fiber member with filler elements at a plurality of axially spaced locations of the tubular fiber member after the inserting step;
a cutting step of cutting the tubular fiber member at an axial position of the tubular fiber member having voids filled with the filling elements after the filling step;
a mounting step of mounting the tubular composite member formed by the tubular fiber member and the filling element obtained after the cutting step on an outer periphery of the stent;
A method for manufacturing an in-vivo indwelling device, comprising: a removal step of removing the core metal member from the tubular fiber member or the tubular composite member at any stage after the filling step and before the attachment step. The filling step includes a step of covering the tubular fiber member with a tubular filling member formed into a tubular shape;
inserting the tubular fiber member covered with the tubular filling member into a tubular heat shrinkable member;
The method according to claim 14, further comprising the step of: heating the tubular heat-shrinkable member at a temperature equal to or higher than the temperature at which the tubular heat-shrinkable member shrinks in diameter. The method for manufacturing an in vivo indwelling device according to claim 14 or 15, characterized in that the polymer in the tubular filling member is oriented in the circumferential direction. The method for manufacturing an in-vivo indwelling device according to any one of claims 14 to 16, characterized in that the melting point of the tubular filling member is lower than the melting point of the fibers. The filling step includes applying a solution containing the filling elements to the tubular fiber member;
and drying the solution. The method of claim 18, characterized in that the solubility of the packing elements in the solvent of the solution is higher than the solubility of the fibers in the solvent.

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