Indwelling object for living body

Abstract

Provided is an indwelling object for a living body that, while preventing dispersal of plaque or thrombi during stent dilation, can suppress inflammation caused by the use of biodegradable polymers at fixation sites for fixing a porous structure to a stent and can suppress decreases in the deliverability of the stent. An indwelling object 100 for a living body is provided with: a dilatable tubular stent 10; a porous structure 20, comprising a first biodegradable polymer and disposed so as to cover the stent 10; and a fixation section 30, comprising a second biodegradable polymer and fixing at least part of the porous structure 20 to the stent 10. The stent 10 comprises a medicament-supporting section 18 that includes a third biodegradable polymer and a medicament, and the time it takes the fixation section 30 to degrade is substantially the same as the time it takes the medicament-supporting section 18 to dissolve, or less than the time it takes the medicament-supporting section 18 to degrade.

Description

Living body incarceration

[0001] The present invention relates to a living body indwelling device.

[0002] A stent is a medical device that is used to treat various diseases caused by stenosis or occlusion of a biological lumen, such as a blood vessel. The stent is delivered to a lesion in the biological lumen by a stent delivery system and then placed there to expand the lesion, such as a stenosis or occlusion, and secure the lumen. A typical stent has linear struts that form the outer periphery of a cylindrical shape with gaps formed therein. After being delivered to the lesion, the stent applies tensile strength (expansion force) to the lesion when expanded (expanded) within the biological lumen. By maintaining this tensile strength for a predetermined period of time, the stent maintains the lesion in an expanded state and secures the lumen of the biological lumen.

[0003] For example, International Publication No. 2006 / 126182 discloses a mesh-covered stent in which a mesh is arranged to cover the outer periphery of a stent in order to prevent peripheral embolism during stent placement. In a mesh-covered stent, the mesh, which has an expandable knitted structure, expands in response to the expansion of the stent, thereby preventing the scattering of plaque or thrombus when the stent is expanded.

[0004] In mesh-covered stents, a polymer mesh may be used to improve the conformability of the mesh (porous structure) when the stent is expanded, improve delivery to the lesion, and reduce the impact that may be exerted on the biological lumen after treatment.The polymer used may be either non-biodegradable or biodegradable.

[0005] However, when components such as the porous structure and the fixing portions for fixing the porous structure to a stent (support element) are formed from non-biodegradable polymers, these components remain in the body as foreign bodies and may cause undesirable events such as restenosis. On the other hand, when biodegradable polymers are used as the above components, they are degraded in the body over time, so the above-mentioned problem of restenosis is less likely or does not occur. However, biodegradable polymers have the problem of easily causing inflammation in tissues during the degradation process.

[0006] The present invention has been made in view of the above-mentioned problems, and aims to provide an in-vivo indwelling device that can prevent the scattering of plaque and thrombus during stent expansion, suppress inflammation by using a biodegradable polymer in the fixing part for fixing a porous structure to the stent, and suppress a decrease in the deliverability of the stent.

[0007] The above object of the present invention can be achieved by any one of the following means (1) to (15).

[0008] (1) A living body indwelling device comprising: an expandable cylindrical stent; a porous structure made of a first biodegradable polymer arranged to cover the stent; and a fixing portion made of a second biodegradable polymer that fixes at least a portion of the porous structure to the stent, wherein the stent has a drug-carrying portion containing a third biodegradable polymer and a drug, and the degradation time of the fixing portion is substantially the same as or shorter than the degradation time of the drug-carrying portion.

[0009] (2) The indwelling device according to (1), wherein the decomposition time of the porous structure is substantially the same as or shorter than the decomposition time of the drug-carrying portion.

[0010] (3) The indwelling device according to (1) or (2), wherein the decomposition time of the porous structure is substantially the same as or shorter than the decomposition time of the fixing part.

[0011] (4) The indwelling device according to any one of (1) to (3), wherein the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer; the second biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer; and the third biodegradable polymer is at least one selected from the group consisting of polylactic acid-polycaprolactone copolymer and polylactic acid.

[0012] (5) The indwelling device according to any one of (1) to (4), wherein the weight average molecular weight of the first biodegradable polymer is 120,000 or more and 180,000 or less, the weight average molecular weight of the second biodegradable polymer is 120,000 or more and 180,000 or less, and the weight average molecular weight of the third biodegradable polymer is 100,000 or more and 120,000 or less.

[0013] (6) The living body indwelling device according to any one of (1) to (5), wherein the porous structure maintains its tensile strength for 7 days or more.

[0014] (7) The living body indwelling device according to any one of (1) to (6), wherein the decomposition time of the porous structure is within 4 months.

[0015] (8) The living body indwelling device according to any one of (1) to (7), wherein the decomposition time of the fixing part is within 4 months.

[0016] (9) The living body indwelling device according to any one of (1) to (8), wherein the decomposition time of the drug-carrying part is 4 months or more.

[0017] (10) The indwelling device according to any one of (1) to (9), wherein the decomposition time of the fixing part is substantially the same as the decomposition time of the drug-carrying part, and the decomposition time of the porous structure is shorter than the decomposition time of the drug-carrying part.

[0018] (11) The living body indwelling device according to any one of (1) to (10), wherein the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are selected from combinations 1 to 20 shown in the table below.

[0019]

[0020]

[0021]

[0022]

[0023]

[0024]

[0025]

[0026] (The composition ratio of each copolymer in the table is a molar ratio.) (12) The indwelling device according to (11), wherein the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are the combination 13 described above.

[0027] (13) The indwelling device according to any one of (1) to (12), wherein the stent is made of a non-biodegradable material, and the drug-carrying portion is disposed only on the portion of the surface of the ring that forms the stent that faces the porous structure.

[0028] (14) The indwelling device according to any one of (1) to (12), wherein the stent is made of a non-biodegradable material, and the drug-carrying portion is arranged so as to cover the entire surface of the ring that forms the stent.

[0029] (15) The indwelling device according to any one of (1) to (12), wherein the entire stent is constituted by the drug-carrying portion.

[0030] FIG. 1 is a schematic plan view showing a stent delivery system including a living body implant according to an embodiment. FIG. 2 is a schematic plan view showing a diametrically contracted state of a stent and a porous structure according to an embodiment. FIG. 3 is a schematic plan view showing a diametrically expanded state of a stent and a porous structure according to an embodiment. FIG. 4 is a partially enlarged view showing a part of a stent and a porous structure in a diametrically expanded state. FIG. 5 is a partially enlarged view showing a part of a stent and a porous structure in a diametrically contracted state. FIG. 6 is an enlarged view of a dashed line portion 6A shown in FIG. 5. FIG. 6 is an enlarged cross-sectional view showing a stent and a porous structure according to a first embodiment, taken along arrows 7A-7A shown in FIG. 6. FIG. 7 is an enlarged cross-sectional view showing a stent and a porous structure according to a second embodiment. FIG. 8 is an enlarged cross-sectional view showing a stent and a porous structure according to a third embodiment.

[0031] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. Note that the following description does not limit the technical scope or meaning of terms described in the claims. Also, the dimensional proportions in the drawings are exaggerated for the convenience of explanation and may differ from the actual proportions.

[0032] The embodiment will be described with reference to FIGS.

[0033] FIG. 1 is a diagram showing a stent delivery system 300 including a living body indwelling device 100 according to an embodiment.

[0034] 2 to 9 are diagrams for explaining the indwelling device 100, the stent 10, and the porous structure 20 according to the embodiment.

[0035] Specifically, Fig. 2 is a schematic plan view showing a diametrically contracted state of the stent 10 and porous structure 20 according to the embodiment. Fig. 3 is a schematic plan view showing a diametrically expanded state of the stent 10 and porous structure 20 according to the embodiment. Fig. 4 is a partial enlarged view of the stent 10 and porous structure 20 shown in Fig. 3. Fig. 5 is a further enlarged view of a portion of the stent 10 and porous structure 20 according to the embodiment. Fig. 6 is an enlarged view of the dashed line portion 6A shown in Fig. 5. Fig. 7 is a cross-sectional view of the indwelling device 100 (the indwelling device 100 according to the first embodiment) taken along arrows 7A-7A shown in Fig. 6. Fig. 8 is a cross-sectional view of the indwelling device 100 according to the second embodiment. Fig. 9 is a cross-sectional view of the indwelling device 100 according to the third embodiment.

[0036] In this specification, the longitudinal direction in which the stent 10 extends is referred to as the "axial direction." The axial direction is the direction from the distal end 10A to the proximal end 10B (or from the proximal end 10B to the distal end 10A) shown in Figure 2. The side of the stent 10 that is inserted into a living body is referred to as the "distal side," and the side opposite the distal side, where the surgeon operates the stent delivery system 300, is referred to as the "proximal side." The direction perpendicular to the axial direction is referred to as the "radial direction" of the indwelling device 100.

[0037] <Living Body Indwelling Device 100> As shown in FIG. 1, the living body indwelling device 100 according to this embodiment is disposed on the outer periphery of an expandable and contractible balloon 220 provided on a balloon catheter 200.

[0038] The balloon catheter 200 has a long catheter body 210 , a balloon 220 provided at the tip of the catheter body 210 , and a hub 230 fixed to the base end of the catheter body 210 .

[0039] The balloon catheter 200 equipped with the indwelling device 100 constitutes a stent delivery system 300. The stent delivery system 300 delivers the indwelling device 100 in a contracted state to the lesion, and expands (expands in diameter) the stent 10 and the porous structure 20 in association with the expansion of the balloon 220, thereby placing the stent 10 and the porous structure 20 in the lesion.

[0040] The balloon catheter 200 can be configured as, for example, a rapid exchange type balloon catheter in which a guide wire W can be introduced from near the distal end of the catheter main body 210 and passed through the distal end side of the balloon 220. The balloon catheter 200 can also be configured as a so-called over-the-wire type balloon catheter.

[0041] For example, an organic polymer material can be used as the material for the balloon 220. Specifically, polymer materials such as polyolefin (e.g., polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or a mixture of two or more of these), polyvinyl chloride, polyamide, polyamide elastomer, polyurethane, polyurethane elastomer, polyimide, fluororesin, or a mixture of these, or an elastic resin material such as two or more of the above polymer materials can be used, and among these, polyamide-based resins can be preferably used as the main material.

[0042] The living body indwelling device 100 will be described in detail below.

[0043] The indwelling device 100 according to this embodiment is used to treat strictures or obstructions that occur in blood vessels, bile ducts, tracheas, esophagus, urethra, or other biological lumens. The stent 10 used in the indwelling device 100 is configured as a so-called balloon-expandable medical device, which is placed in a crimped state on a folded balloon 220, and is expanded and placed at the lesion after being delivered to the lesion.

[0044] 2, 4, 5, 6, and 7, the indwelling device 100 comprises an expandable cylindrical stent 10, a porous structure 20 made of a first biodegradable polymer arranged to cover the stent 10, and a fixing portion 30 made of a second biodegradable polymer that fixes at least a portion of the porous structure 20 to the stent 10, the stent 10 having a drug-carrying portion 18 containing a third biodegradable polymer and a drug, and the degradation time of the fixing portion 30 is substantially the same as or shorter than the degradation time of the drug-carrying portion 18.

[0045] In the above-described indwelling device, the stent is covered with a porous structure, which prevents plaque and thrombus from scattering when the stent is expanded. Furthermore, in the above-described indwelling device, the porous structure is fixed to the stent by an anchoring portion, which prevents the porous structure from falling off the stent. This prevents a decrease in the deliverability of the stent. Furthermore, in the above-described indwelling device, the drug continues to be released from the drug-carrying portion until the anchoring portion is decomposed and disappears after a certain period of time has elapsed after placement. This effectively prevents the onset of inflammation caused by the anchoring portion made of a biodegradable polymer.

[0046] 2 to 4, the stent 10 has a cylindrical shape extending in the axial direction. The porous structure 20 is disposed so as to cover the outer periphery of the stent 10, and has the same cylindrical shape as the stent 10.

[0047] As shown in FIGS. 2, 3, 4 and 5, the stent 10 has a distal end 10A, a proximal end 10B, and a fixing portion 30 for fixing the porous structure 20 to the stent 10.

[0048] The stent 10 is configured to be capable of radial expansion (expansion to the states shown in FIGS. 3 and 4) and contraction (contraction to the state shown in FIG. 2).

[0049] As shown in Figures 3 to 6, the stent 10 has linear rings 11 that form the outer periphery of a cylindrical shape with gaps formed therein, and link portions 12 that connect the rings 11 with gaps defined between adjacent linear rings 11 in the axial direction.

[0050] The rings 11 extend circumferentially around the stent 10 in an axially reciprocating wave pattern.

[0051] As shown in Figure 4, the wavy ring 11 has a plurality of first strut portions 15 each consisting of a straight or curved line, a plurality of second strut portions 16 each consisting of a straight or curved line, and a curved portion 17 formed between the first strut portion 15 and the second strut portion 16.

[0052] As shown in FIG. 4, the ring 11 also has a plurality of third strut portions 14, which are adjacent to one side of the link portion 12 in the axial direction and are provided in pairs in the circumferential direction, and which are configured as straight or curved lines.

[0053] The rings 11 are arranged sequentially along the axial direction. Axially adjacent rings 11 are connected and integrated by links 12. Therefore, by increasing or decreasing the number of rings 11, it is possible to easily obtain a stent 10 having a desired axial length.

[0054] 6 and 7, a drug-carrying portion 18 may be provided on at least a portion of the outer surface of the stent 10. For example, the drug-carrying portion 18 may be disposed on the first strut portion 15 and the third strut portion 14 of the ring 11 shown in FIG.

[0055] In this embodiment, the drug-carrying portion 18 is not provided on the link portion 12. The portion of a predetermined range including the link portion 12 where the drug-carrying portion 18 is not provided constitutes the exposed portion 13. Specifically, the curved portion 17 of the ring 11 and the link portion 12 (areas where stress concentrates and / or distortion occurs as the stent 10 expands) are configured as the exposed portion 13. Because the drug-carrying portion 18 is not formed on the curved portion 17 of the ring 11 and the link portion 12, it is possible to prevent the drug-carrying portion 18 from peeling off or falling off due to stress concentrating on the drug-carrying portion 18 and causing bending or distortion when the stent 10 expands.

[0056] 6 shows a plan view of a portion of the drug-carrying portion 18 formed on the outer surface 10b of the stent 10. In this specification, for convenience of illustration, the drug-carrying portion 18 is omitted from the drawings other than FIGS.

[0057] The drug coated on the outer surface 10b of the stent 10 is supported by a polymer to form the drug-supported portion 18. The polymer is preferably a biodegradable polymer. In this case, after the stent 10 is placed in a living body, the drug is gradually released while the polymer is biodegraded, thereby more reliably preventing restenosis at the stent placement site in the living body and suppressing inflammation caused by the polymer. Details of the type of drug and the polymer (third biodegradable polymer) used in the drug-supported portion 18 will be described later.

[0058] A primer coating layer (not shown) may be disposed between the drug-carrying portion 18 and the outer surface 10b of the stent 10. Any primer can be selected to form the primer coating layer, taking into consideration its adhesiveness to the polymer contained in the drug-carrying portion 18 and its adhesiveness to the outer surface 10b of the stent 10. By providing a primer coating layer, the peel resistance of the drug-carrying portion 18 can be improved.

[0059] The porous structure 20 is disposed so as to cover the outer periphery of the stent 10 and is capable of expanding (expanding in diameter) in accordance with the expansion (diameter expansion) of the stent 10 .

[0060] As shown in FIGS. 5 and 6, the porous structure 20 has voids 24a that penetrate the porous structure 20 in the thickness direction, and a skeleton 24b that defines the voids 24a.

[0061] The indwelling device 100 has the porous structure 20 disposed on the outer periphery of the stent 10, and therefore when the stent 10 is expanded in a blood vessel, the porous structure 20 can be biased against the blood vessel in accordance with the expansion of the stent 10. Therefore, the indwelling device 100 can prevent the porous structure 20 from coming off or shifting from the indwelling site due to the pressure of the blood flowing in the blood vessel.

[0062] The porous structure 20 has a cylindrical shape extending in the axial direction, and has a mesh structure consisting of voids 24a and a skeleton 24b.

[0063] As shown in Figures 4, 5, and 6, the size of each of the multiple voids 24a in the porous structure 20 is preferably smaller than the area of ​​the gaps between the rings 11 of the stent 10. By adopting such a configuration, it is possible to prevent plaque and thrombus from scattering as the stent 10 expands. On the other hand, it is preferable that the size of the voids 24a be larger than the area of ​​a single blood cell contained in blood. This allows blood cells to pass through the voids 24a. Furthermore, the voids 24a enable the porous structure 20 to be extensible. Therefore, when the stent 10 expands, the porous structure 20 also elongates in the circumferential direction in accordance with the expansion of the stent 10, thereby exhibiting good follow-up (expandability) to the expansion of the stent 10.

[0064] The porous structure 20 can be made of, for example, a knitted fabric, a woven fabric (braid), or a molded product (a member such as a membrane with slits formed therein). When the porous structure 20 is a knitted fabric, the porous structure 20 can be made of a stockinette stitch. By making the porous structure 20 of a stockinette stitch, it is possible to prevent the axial length of the porous structure 20 from shortening as the stent 10 expands. When the porous structure 20 is a woven fabric, the woven fabric is made of a known weaving method. Alternatively, the porous structure 20 may be made of a molded product obtained by drilling holes in a tubular body formed by injection molding or the like. The size, shape, and number of the stitches and weaves of the porous structure 20 are not particularly limited as long as they are capable of preventing peripheral embolism during the expansion of the stent 10.

[0065] The fixing portion 30 can be provided, for example, so as to fix at least a part of the porous structure 20 to the stent 10 at a position excluding the distal end 10A and proximal end 10B of the stent 10. In this specification, the distal end 10A of the stent 10 refers to "the region at the most distal end of the stent 10 where the link portion 12 arranged at the most distal end is not provided." Also, in this specification, the proximal end 10B of the stent 10 refers to "the region at the most proximal end of the stent 10 where the link portion 12 arranged at the most proximal end is not provided."

[0066] The fixing portion 30 can be provided, for example, so that at least a portion of the porous structure 20 fixed to the stent 10 is embedded in the fixing portion 30 .

[0067] The fixing parts 30 can be provided, for example, on all of the link parts 12 included in the stent 10. The link parts 12 undergo little change in axial geometry as the stent 10 expands. Therefore, in the link parts 12, tension on the porous structure 20 associated with the expansion of the stent 10 does not occur when the stent 10 expands, and the fixing parts 30 provided on the link parts 12 can suitably prevent peeling or damage to the porous structure 20.

[0068] As described above, the link portions 12 are not provided with the drug-carrying portions 18. Therefore, as shown in Fig. 6 , the fixing portions 30 fix the porous structure 20 directly to the stent 10 at the exposed portions 13 of the stent 10 where no drug is applied. In other words, the fixing portions 30 are disposed directly on the link portions 12 of the stent 10. This configuration can improve the fixing force that fixes the porous structure 20 to the stent 10 compared to a configuration in which the fixing portions 30 are fixed to the stent 10 via the drug-carrying portions 18.

[0069] As described above, the fixing part 30 is provided in the exposed part 13 of the stent 10 where no drug is applied, so as to directly fix the porous structure 20 to the stent 10. Therefore, even if the fixing part 30 is welded by heating, the drug-carrying part 18 is not present in the heated area and its surrounding area, so that the efficacy of the drug can be prevented from being lost.

[0070] When the fixing material is fixed to the stent 10 via the drug-carrying portion 18, it is preferable to use a method that does not require heating or is less affected by heating, such as an adhesive.

[0071] As shown in Fig. 6, the loop portions 21 of the mesh knitted along the circumferential direction of the porous structure 20 can be fixed to the stent 10 via the fixing portions 30. It is preferable that the portions fixed by the fixing portions 30 include at least the loop portions 21. With this configuration, the loop portions 21 extending along the circumferential direction can be fixed to the stent 10, so that a long distance of the porous structure 20 can be embedded in the fixing material, thereby improving the fixing force.

[0072] The following describes preferred materials and effects of the living body indwelling device 100, as well as preferred arrangements of the drug carrying portion 18, etc.

[0073] 7, the drug-carrying portion 18 can be disposed only in at least a portion 19a (hereinafter referred to as "opposing portion 19a") facing the porous structure 20 in a cross section perpendicular to the axial direction of the surface 19 of the ring 11 that forms the stent 10. However, as will be described later, the drug-carrying portion 18 may have any form as long as it is present on at least a portion of the surface 19 of the ring 11 that forms the stent 10 or on at least a portion of the stent 10 itself.

[0074] Furthermore, the drug carrying portion 18 may be present in at least some or all of the multiple first strut portions 15, second strut portions 16, and third strut portions 14 of the ring 11, and may be present or absent in the multiple link portions 12 and / or curved portions 17. Preferably, the drug carrying portion 18 is present in the multiple first strut portions 15, second strut portions 16, and third strut portions 14, and is not present in the link portions 12 and curved portions 17. This reduces the phenomenon of the drug carrying portion 18 peeling off in the link portions 12 and curved portions 17, where stress concentration is likely to occur when the stent 10 is expanded.

[0075] In the first embodiment, the drug-carrying portion 18 is formed only on the facing portion 19a of the ring 11. According to the first embodiment, the drug-carrying portion 18 is selectively disposed on the facing portion 19a, and therefore the drug contained in the drug-carrying portion 18 is selectively released only from the side where the porous structure 20 is disposed (the facing portion 19a side). Therefore, according to the first embodiment, an inflammatory reaction induced by the porous structure 20 can be more effectively suppressed or prevented with a smaller amount of drug than when the drug-carrying portion 18 is disposed so as to cover the entire surface 19 of the ring 11. In other words, the risk of inflammation caused by contact between the porous structure 20 and biological tissue near the facing portion 19a can be effectively reduced or eliminated.

[0076] In the first embodiment, the shape and size (cross-sectional shape, area provided on opposing portion 19a, etc.) of drug support portion 18 are not particularly limited and can be set appropriately depending on the cross-sectional shape and size of ring 11. For example, when the cross-sectional shape of ring 11 is square, approximately square, rectangular, or approximately rectangular, drug support portion 18 can be formed over the entire area of ​​the surface of ring 11 that can come into contact with porous structure 20.

[0077] In the first embodiment, the thickness of the drug carrying portion 18 is not particularly limited and is appropriately selected depending on the desired decomposition time, drug content, etc. The thickness of the drug carrying portion 18 can be, for example, 1 to 20 μm.

[0078] In a second embodiment of the present invention, as shown in FIG. 8 , the stent 10 is made of a non-biodegradable material, and the drug-carrying portion 18 can be arranged to cover the entire area of ​​the surface 19 of the ring 11 forming the stent 10 in a cross section perpendicular to the axial direction. According to the second embodiment, the drug-carrying portion 18 is arranged in areas other than the contact area with the porous structure 20. Therefore, according to the second embodiment, the drug concentration can be maintained more sufficiently than when the drug-carrying portion 18 is arranged only on the opposing portion 19 a of the ring 11, and therefore, inflammatory reactions induced by the porous structure 20 can be sufficiently suppressed or prevented. Furthermore, in the indwelling device 100, for example, an anti-inflammatory agent can be arranged on the side where the porous structure 20 comes into contact with biological tissue, and another drug that can be used to treat the target can be arranged in the other covered areas. Therefore, according to the second embodiment, inflammatory reactions induced by the porous structure 20 can be more effectively suppressed or prevented, while other necessary treatments can be performed simultaneously.

[0079] In the second embodiment, the thickness of the drug support portion 18 is not particularly limited and is appropriately selected depending on the decomposition time, drug content, etc. The thickness of the drug support portion 18 can be, for example, 0.5 to 10 μm.

[0080] In the third embodiment of the present invention, as shown in FIG. 9 , the entire stent 10 (all of the rings 11 forming the stent 10) is configured with the drug-carrying portion 18. In other words, the stent 10 itself can function as the drug-carrying portion 18. According to the third embodiment, since it is not necessary to separately form the drug-carrying portion 18 on the stent 10, the manufacturing process can be reduced, which is preferable from the viewpoint of mass production. Furthermore, as in the second embodiment, for example, a large amount of anti-inflammatory agent can be placed on the contact region side (facing portion 19 a side) of the stent 10 that comes into contact with the porous structure 20, and another drug that can be used for the treatment of the target can be placed in the remaining portion. Therefore, according to the third embodiment, it is possible to more effectively suppress or prevent an inflammatory response induced by the porous structure 20 and simultaneously perform other necessary treatments.

[0081] Of the first to third embodiments, the first and second embodiments are preferred, with the first embodiment being more preferred, from the viewpoints of further suppressing and preventing inflammatory reactions, higher tensile strength of the stent 10, and a longer period during which the tensile strength is maintained.

[0082] In the first and second embodiments, non-biodegradable materials that can be used for the stent 10 include carbon fiber, metal materials, and polymer materials. Preferably, the non-biodegradable material is a metal material or a polymer material. From the viewpoint of further reducing inflammation, it is particularly preferable that the non-biodegradable material be a metal material. When the stent 10 is made of a metal material, the metal material is not particularly limited, and metal materials commonly used in the stent manufacturing field can be used. Specific examples include stainless steels such as SUS304, SUS316, SUS316L, SUS420J2, and SUS630; tantalum; titanium; nickel-titanium alloys; tantalum-titanium alloys; nickel-aluminum alloys; Inconel; gold; platinum; iridium; tungsten; and cobalt-chromium (Co—Cr) alloys. Among stainless steels, SUS316L is preferred, as it has the best corrosion resistance. Among cobalt-based alloys, MP35N, L605, and the like are preferred. Furthermore, when the stent 10 is made of a polymer material, the polymer material to be used is not particularly limited, and may be any polymer material that is commonly used in the field of the product of the stent 10. Specific examples include polyolefins such as polyethylene and polypropylene, aromatic polyesters such as polyethylene terephthalate, cellulose-based polymers such as cellulose acetate and cellulose nitrate, and fluorine-containing polymers such as polytetrafluoroethylene and tetrafluoroethylene-ethylene copolymers.

[0083] The stent 10 can be suitably formed from a material appropriately selected from the materials exemplified above depending on the application site, etc. For example, when the stent 10 is formed from a metal material, the metal material has excellent strength, so the indwelling device 100 can be placed more reliably at the lesion site. When the stent 10 is formed from a polymer material, the polymer material has excellent flexibility, so the indwelling device 100 can be effectively delivered to the lesion site.

[0084] Furthermore, when the stent 10 is a self-expanding type, a superelastic alloy such as a nickel-titanium alloy is preferred because it requires the ability to return to its original shape. On the other hand, when the stent 10 is a balloon-expanding type, stainless steel is preferred because it is less likely to return to its original shape after expansion. Furthermore, when the stent 10 is made of carbon fiber, it exhibits excellent effects in that it is high in strength, has excellent flexibility, and is highly safe in vivo.

[0085] The stent 10 is not particularly limited in terms of material, shape, size, etc., as long as it can be placed at a lesion occurring in a lumen in a living body, such as a blood vessel, bile duct, trachea, esophagus, or urethra. For example, when used in a coronary artery of the heart, the outer diameter of the stent 10 before expansion is typically, for example, 1.0 to 3.0 mm. The wall thickness of the stent 10 (thickness in the cross-sectional views shown in Figures 7 to 9) is, for example, 0.05 to 0.25 mm. The length (axial length) of the stent 10 is, for example, 5 to 50 mm.

[0086] The method for manufacturing the stent 10 is not particularly limited, and may be appropriately selected from commonly used manufacturing methods depending on the structure and material of the stent 10. For example, a manufacturing method utilizing an etching technique such as laser etching or chemical etching, or a laser cutting technique may be selected.

[0087] The indwelling device 100 according to the present invention comprises an expandable tubular stent 10 having a drug-carrying portion 18 containing a third biodegradable polymer and a drug, a porous structure 20 made of a first biodegradable polymer arranged to cover the stent 10, and a fixing portion 30 made of a second biodegradable polymer that fixes at least a portion of the porous structure 20 to the stent 10.

[0088] In the present invention, the degradation time of the fixing part 30 is substantially the same as or shorter than the degradation time of the drug-carrying part 18 (the degradation time of the fixing part 30 is less than or equal to the degradation time of the drug-carrying part 18). In a bioinstrument 100 in which a porous structure 20 is fixed to a stent 10 via the fixing part 30, if the fixing part 30 is made of a non-biodegradable material, the fixing part 30 may remain in the body as a foreign body and cause undesirable events such as restenosis. On the other hand, even if the fixing part 30 is made of a biodegradable material, many biodegradable materials cause inflammation during the degradation process. However, in the present invention, the drug-carrying part 18 decomposes simultaneously with or after the decomposition of the fixing part 30. Therefore, the drug continues to be released from the drug-carrying part 18 into the biological tissue with which the fixing part 30 comes into contact until the fixing part 30 decomposes. Therefore, the indwelling device 100 according to the present invention can effectively prevent and suppress inflammatory reactions associated with the degradation of the fixing part 30 (second biodegradable polymer) during placement. On the other hand, if the degradation time of the fixing part 30 is longer than the degradation time of the drug-carrying part 18 (degradation time of the fixing part 30 > degradation time of the drug-carrying part 18), the fixing part 30 will remain beyond the drug elution period, which may cause adverse events such as restenosis.

[0089] Here, the decomposition time of the fixing part 30 can be shorter than the decomposition time of the drug-carrying part 18. With this configuration, the drug-carrying part 18 decomposes and disappears after the fixing part 30 decomposes and disappears. The drug continues to be released from the drug-carrying part 18 to the biological tissue with which the fixing part 30 comes into contact throughout the entire period that the fixing part 30 is present. Therefore, with this configuration, inflammatory reactions associated with the decomposition of the fixing part 30 (second biodegradable polymer) can be effectively prevented or suppressed. Here, the difference between the decomposition time of the fixing part 30 and the decomposition time of the drug-carrying part 18 (= decomposition time of the drug-carrying part 18 - decomposition time of the fixing part 30) is preferably 0.1 to 15 months, more preferably 0.5 to 12 months. In this specification, one month is defined as 30 days.

[0090] Alternatively, the decomposition time of the fixing part 30 can be substantially the same as the decomposition time of the drug-carrying part 18. With this configuration, the drug-carrying part 18 decomposes and disappears around the same time as the fixing part 30 decomposes and disappears. Therefore, for most of the time the fixing part 30 is present, the drug continues to be released from the drug-carrying part 18 to the biological tissue with which the fixing part 30 comes into contact. Therefore, with this configuration, inflammatory reactions associated with the decomposition of the fixing part 30 (second biodegradable polymer) can be effectively prevented or suppressed. Here, "the decomposition time of the fixing part 30 is substantially the same as the decomposition time of the drug-carrying part 18" means that the difference between the decomposition time of the fixing part 30 and the decomposition time of the drug-carrying part 18 is within 24 hours, preferably within 10 hours, more preferably within 5 hours, and particularly preferably within 2 hours. Particularly preferably, the decomposition time of the fixing part 30 is the same as the decomposition time of the drug-carrying part 18 (the difference is 0 hours). Preferably, the decomposition time of the fixing part 30 is the same as the decomposition time of the drug carrying part 18 (decomposition time of the fixing part 30 = decomposition time of the drug carrying part 18).

[0091] In one embodiment of the present invention, the decomposition time of the fixing part 30 is 0.1 to 15 months shorter than the decomposition time of the drug carrying part 18, or the decomposition time of the fixing part 30 is substantially the same as the decomposition time of the drug carrying part 18. In one embodiment of the present invention, the decomposition time of the fixing part 30 is 0.5 to 12 months shorter than the decomposition time of the drug carrying part 18, or the decomposition time of the fixing part 30 is the same as the decomposition time of the drug carrying part 18.

[0092] Other preferable relationships among the decomposition time of the fixing part 30, the decomposition time of the drug carrying part 18, and the decomposition time of the porous structure 20 will be described below.

[0093] Regarding the relationship between the decomposition time of the porous structure 20 and the decomposition time of the drug-carrying portion 18, it is preferable that the decomposition time of the porous structure 20 be substantially the same as or shorter than the decomposition time of the drug-carrying portion 18 (the decomposition time of the porous structure 20≦the decomposition time of the drug-carrying portion 18). As described above, the indwelling device 100 placed in a living body (in a living lumen) is likely to cause inflammation at the contact portion with the living tissue. On the other hand, in the case of the above-described decomposition time relationship, the drug is continuously released from the drug-carrying portion 18 to the living tissue with which the porous structure 20 contacts for most of the time the porous structure 20 is present. Therefore, this configuration can more effectively prevent or suppress inflammatory reactions in living tissues associated with the decomposition of the porous structure 20 (first biodegradable polymer). Therefore, it is possible to simultaneously suppress or prevent peripheral embolism and reduce or eliminate the risk of inflammation in living tissues due to contact with the porous structure 20.

[0094] The decomposition time of the porous structure 20 can be shorter than the decomposition time of the drug-carrying portion 18. With this configuration, the drug-carrying portion 18 decomposes and disappears after the porous structure 20 decomposes and disappears. The drug is continuously released from the drug-carrying portion 18 to the biological tissue with which the porous structure 20 contacts throughout the entire period the porous structure 20 is present. Therefore, with this configuration, inflammatory reactions associated with the decomposition of the porous structure 20 (first biodegradable polymer) can be effectively prevented or suppressed. Here, the difference between the decomposition time of the porous structure 20 and the decomposition time of the drug-carrying portion 18 (=decomposition time of the drug-carrying portion 18 - decomposition time of the porous structure 20) is preferably 0.2 months or more and 15 months or less, preferably 0.5 months or more and 12 months or less, and preferably 1.0 month or more and 3.0 months or less. Providing such a time difference allows for a better balance between the suppression and prevention of peripheral embolism and the reduction or elimination of the risk of tissue inflammation due to contact with the porous structure 20.

[0095] Alternatively, the decomposition time of the porous structure 20 can be substantially the same as the decomposition time of the drug-carrying portions 18. With this configuration, the drug-carrying portions 18 decompose and disappear around the same time that the porous structure 20 decomposes and disappears. Therefore, for most of the time the porous structure 20 is present, the drug continues to be released from the drug-carrying portions 18 to the biological tissue with which the porous structure 20 comes into contact. Therefore, with this configuration, inflammatory reactions associated with the decomposition of the porous structure 20 (first biodegradable polymer) can be effectively prevented or suppressed. Here, "the decomposition time of the porous structure 20 is substantially the same as the decomposition time of the drug-carrying portions 18" means that the difference between the decomposition time of the porous structure 20 and the decomposition time of the drug-carrying portions 18 is within 24 hours, preferably within 10 hours, more preferably within 5 hours, and particularly preferably within 2 hours. Particularly preferably, the decomposition time of the porous structure 20 is the same as the decomposition time of the drug-carrying portions 18 (the difference is 0 hours).

[0096] In one embodiment of the present invention, the decomposition time of the porous structure 20 is 0.2 to 15 months shorter than the decomposition time of the drug-carrying portion 18, or is substantially the same as the decomposition time of the drug-carrying portion 18. Because the porous structure 20 is disposed so as to cover the stent 10, the contact area between the porous structure 20 and the biological tissue is larger than the contact area between the stent 10 and the biological tissue. Therefore, the risk of inflammation associated with the degradation of the porous structure 20 (first biodegradable polymer) is greater for the porous structure 20 than for the fixing portion 30. Therefore, it is preferable that the drug be continuously released from the drug-carrying portion 18 to the biological tissue with which the porous structure 20 comes into contact throughout the entire period during which the porous structure 20 exists. That is, in one embodiment of the present invention, the decomposition time of the porous structure 20 is 0.5 to 12 months shorter than the decomposition time of the drug-carrying portion 18. In one embodiment of the present invention, the decomposition time of the porous structure 20 is 1.0 to 3.0 months shorter than the decomposition time of the drug-carrying portion 18.

[0097] At least a portion of the porous structure 20 is fixed to the stent 10 via the fixing portion 30 so that the porous structure 20 does not come off the stent 10 during the placement operation or during the placement period. It is preferable that the porous structure 20 continues to be at least partially fixed to the stent 10 via the fixing portion 30 throughout the placement period in the biological lumen. Therefore, it is preferable that the degradation time of the porous structure 20 is substantially the same as or shorter than the degradation time of the fixing portion 30 (degradation time of the porous structure 20≦degradation time of the fixing portion 30).

[0098] Here, the decomposition time of the porous structure 20 can be shorter than the decomposition time of the fixing part 30. In this configuration, the fixing part 30 decomposes and disappears after the porous structure 20 decomposes and disappears. The porous structure 20 is fixed to the stent 10 via the fixing part 30 throughout the entire period that the porous structure 20 exists. For example, even when the indwelling device 100 according to the present invention is placed in the coronary artery of a patient with acute myocardial infarction, it is possible to prevent the porous structure 20 from slipping or falling off from the indwelling device 100 (stent 10) due to vascular pulsation. Here, the difference between the decomposition time of the porous structure 20 and the decomposition time of the fixing part 30 (=decomposition time of the fixing part 30−decomposition time of the porous structure 20) is, for example, 0.1 to 4 months, preferably 0.2 to 3 months, and more preferably 1.0 to 2.5 months.

[0099] Alternatively, the decomposition time of the porous structure 20 can be made substantially the same as the decomposition time of the fixing part 30. With this configuration, the fixing part 30 decomposes and disappears around the same time as the porous structure 20 decomposes and disappears. Therefore, the porous structure 20 is fixed to the stent 10 via the fixing part 30 for most of the time that the porous structure 20 exists. For example, even when the indwelling device 100 according to the present invention is placed in the coronary artery of a patient with acute myocardial infarction, it is possible to prevent the porous structure 20 from slipping or falling off from the indwelling device 100 (stent 10) due to vascular pulsation. Here, "the decomposition time of the porous structure 20 is substantially the same as the decomposition time of the fixing part 30" means that the difference between the decomposition time of the porous structure 20 and the decomposition time of the fixing part 30 is within 24 hours, preferably within 10 hours, more preferably within 5 hours, and particularly preferably within 2 hours. It is particularly preferable that the decomposition time of the porous structure 20 is the same as the decomposition time of the fixing part 30 (decomposition time of the porous structure 20 = decomposition time of the fixing part 30).

[0100] In one embodiment of the present invention, the decomposition time of the porous structure 20 is 0.1 to 4 months shorter than the decomposition time of the fixing part 30, or the decomposition time of the porous structure 20 is substantially the same as the decomposition time of the fixing part 30. It is preferable that the porous structure 20 is continuously and reliably suppressed and prevented via the fixing part 30 during the indwelling period so that displacement or detachment due to changes in the biological lumen, such as vascular pulsation, does not occur. For this reason, it is preferable that the fixing part 30 continues to exist throughout the entire period during which the porous structure 20 exists. On the other hand, it is preferable that the fixing part 30 decomposes and disappears quickly after the porous structure 20 decomposes and disappears. That is, in one embodiment of the present invention, the decomposition time of the porous structure 20 is 0.2 to 3 months shorter than the decomposition time of the fixing part 30. In one embodiment of the present invention, the decomposition time of the porous structure 20 is 1.0 to 2.5 months shorter than the decomposition time of the fixing part 30.

[0101] From the viewpoint of more effective prevention and suppression of inflammation and the like at the contact portion where the living body implant 100 comes into contact with biological tissue (hereinafter referred to as the "contact portion"), it is preferable that the decomposition time of the drug-carrying portion 18 is longer than both the decomposition time of the fixing portion 30 and the decomposition time of the porous structure 20. Furthermore, in order to prevent the porous structure from slipping or falling off from the living body implant 100 (stent 10), it is preferable that the decomposition time of the porous structure 20 is equal to or shorter than the decomposition time of the fixing portion 30. That is, in one embodiment of the present invention, the decomposition time of the porous structure 20 is substantially the same as or shorter than the decomposition time of the fixing portion 30, and the decomposition time of the fixing portion 30 is substantially the same as or shorter than the decomposition time of the drug-carrying portion 18 (decomposition time of the porous structure 20≦decomposition time of the fixing portion 30≦decomposition time of the drug-carrying portion 18). In one embodiment of the present invention, the decomposition time of the porous structure 20 is shorter than the decomposition time of the fixing part 30, and is substantially the same as the decomposition time of the drug carrying part 18 (decomposition time of the porous structure 20 < decomposition time of the fixing part 30 ≈ decomposition time of the drug carrying part 18). In one embodiment of the present invention, the decomposition time of the porous structure 20 is shorter than the decomposition time of the fixing part 30 by 0.2 months or more and 3 months or less, and the difference between the decomposition time of the fixing part 30 and the decomposition time of the drug carrying part 18 (= decomposition time of the drug carrying part 18 - decomposition time of the fixing part 30) is 0 to 5 hours or 0 to 2 hours. In one embodiment of the present invention, the decomposition time of the porous structure 20 is shorter than the decomposition time of the fixing part 30 by 1.0 month or more and 2.5 months or more, and the decomposition time of the fixing part 30 is the same as the decomposition time of the drug carrying part 18.

[0102] The degradation time of the porous structure 20 can be appropriately selected depending on the target disease, the state and severity of the disease, the placement site, etc. The degradation time of the porous structure 20 is preferably within 4 months, more preferably from 1 month to 3.5 months, and particularly preferably from 1.5 months to 2 months. Within this degradation time, the porous structure 20 can suppress the scattering of plaque and thrombus when the indwelling device 100 is placed, while an endothelial cell layer can be sufficiently formed on the indwelling device 100 (stent 10).

[0103] In this specification, the "degradation time" of the porous structure 20, the fixing portion 30, the drug carrying portion 18, the first biodegradable polymer, the second biodegradable polymer and the third biodegradable polymer is a value measured according to the method described below.

[0104] [Method for Measuring Degradation Time] 0.3 mg of each of the porous structure 20, the fixing portion 30, the drug-carrying portion 18, the first biodegradable polymer, the second biodegradable polymer, or the third biodegradable polymer (collectively referred to as "sample") was weighed into a screw-cap test tube. Next, phosphate-buffered saline (PBS) at pH 7.4 was poured into the test tube up to the 15 ml line. The phosphate-buffered saline (PBS) was used as a simulated body fluid. The test tube was then stored in a 37°C incubator for a predetermined period (0, 1, 3, 7, 14, and 30 days, or 2, 3, 4, 6, 9, and 12 months) to allow hydrolysis to occur. After the predetermined period, the screw-cap test tube was removed from the incubator, and the PBS was sucked out of the screw-cap test tube with a Pasteur pipette. The water in the test tube was then completely evaporated by vacuum drying. Thereafter, a mobile phase solvent (hexafluoroisopropanol containing 5 mM sodium trifluoroacetate) is added to the test tube so that the sample concentration becomes 1 mg / ml, and the sample is completely dissolved. Then, the weight-average molecular weight (Mw) and number-average molecular weight (Mn) are measured according to the following method.

[0105] (Method for measuring weight-average molecular weight (Mw) and number-average molecular weight (Mn)) The weight-average molecular weight (Mw) and number-average molecular weight (Mn) are values ​​measured by gel permeation chromatography (GPC) using polymethyl methacrylate as a standard substance under the following measurement conditions: (Measurement conditions) Apparatus: Semi-micro GPC system LC-VP (manufactured by Shimadzu Corporation) Detector: Shodex (registered trademark) RI-104 (manufactured by Showa Denko K.K.) Column: Shodex (registered trademark) GPC LF-404 (manufactured by Showa Denko K.K.) Column temperature: 40°C Mobile phase solvent: hexafluoroisopropanol (HFIP) containing 5 mM sodium trifluoroacetate Sample concentration: 1 mg / ml Flow rate: 0.30 mL / min Injection volume: 10 μL Sample preparation: 1 mL of mobile phase solvent is added to 1 mg of the sample to be measured, and the solution is dissolved, and then filtered through a 0.45 μm PTFE membrane filter.

[0106] Next, a logarithmic plot of the obtained number average molecular weight (Mn) was created, and the time at which Mn became 100 was determined from the linear regression equation of this plot, and this time was taken as the decomposition time.

[0107] Providing a porous structure 20 on a stent 10 (particularly a metal stent) can suppress peripheral embolism associated with the scattering of embolic material (e.g., thrombus, plaque) during placement of the stent 10. Because the porous structure 20 is made of a biodegradable polymer (first biodegradable polymer), components (e.g., knitted yarns) constituting the porous structure 20 gradually break and fall off from areas of high stress during placement, creating holes. This can cause the porous structure 20 to lose its ability to retain embolic material such as thrombus or plaque, and the fallen fragments may scatter to the peripheral blood vessel, potentially leading to peripheral embolism. Furthermore, once this process has progressed to a certain extent, the porous structure 20 can no longer maintain its shape (e.g., a cylindrical shape). Therefore, it is preferable that the porous structure 20, together with the stent 10, exert tensile strength to expand the biological lumen in which it is placed and maintain that tensile strength throughout the placement period. For example, when the indwelling device 100 according to the present invention is placed in a relatively small-diameter coronary artery in a patient with a heart disease such as acute myocardial infarction, the thrombus retraction period is approximately 7 days. Therefore, when such a disease is treated, the tensile strength maintenance period of the porous structure 20 is preferably 7 days or more, more preferably 9 days or more, and particularly preferably 15 days or more. In the above case, the upper limit of the tensile strength maintenance period of the porous structure 20 is, for example, 30 days or less, preferably 25 days or less. Within such a period, an endothelial cell layer can be sufficiently formed on the indwelling device 100 (stent 10). Furthermore, when the indwelling device 100 according to the present invention is placed in a relatively large-diameter carotid artery in a patient with carotid artery stenosis, for example, it has been reported that plaque can be dispersed from the mesh portion of the porous structure 20 even 1 to 1.5 months after placement. Therefore, when targeting such diseases, the tensile strength retention period of the porous structure 20 is preferably one month or more, more preferably two months or more. In the above case, the upper limit of the tensile strength retention period of the porous structure 20 is, for example, six months or less, preferably three months or less. Within such a period, an endothelial cell layer can be sufficiently formed on the indwelling device 100 (stent 10).

[0108] In this specification, the "tensile strength retention period" refers to the period during which the porous structure 20 can maintain its tensile strength, and specifically, is a value measured according to the following method.

[0109] [Method for measuring tensile strength maintenance period] It has been reported that the period during which the tensile strength of Dexon (registered trademark) (PGA suture), Vicryl (registered trademark) (PGLA9010 suture), and Monocryl (registered trademark) (PGCL7525 suture) becomes 50% or less is approximately 2 to 3 weeks (e.g., Biomed. Mater. Res., 49(1): 25-35, 2000). On the other hand, when the weight average molecular weight (Mw) of these sutures was measured according to the following method, it was found that the weight average molecular weight had decreased to about 20,000 after 2 weeks. From the above results, the weight average molecular weight of the porous structure (or the first biodegradable polymer) was measured according to the following method, and the storage period required for the weight average molecular weight (Mw) to become 20,000 or less was defined as the "tensile strength maintenance period of the porous structure 20".

[0110] 0.3 mg of the porous structure 20 or the first biodegradable polymer (collectively referred to as the "sample") was weighed into a screw-cap test tube. Next, phosphate-buffered saline (PBS) at pH 7.4 was poured into the test tube up to the 15 ml line. The phosphate-buffered saline (PBS) was used as a simulated body fluid. The test tube was then stored in a constant temperature bath at 37°C to allow hydrolysis to occur. Every day from the seventh day onwards, the screw-cap test tube was removed from the constant temperature bath, and the PBS was sucked out of the screw-cap test tube with a Pasteur pipette. The water in the test tube was then completely evaporated by vacuum drying. A mobile phase solvent (hexafluoroisopropanol containing 5 mM sodium trifluoroacetate) was then added to the test tube to achieve a sample concentration of 1 mg / ml. The sample was then completely dissolved, and the weight-average molecular weight (Mw) after storage for a predetermined period was measured in the same manner as described in the "Method for measuring decomposition time" above.

[0111] The degradation time of the fixing part 30 can be appropriately selected depending on the target disease, the state and severity of the disease, the placement site, and further the degradation times of the porous structure 20 and the drug-carrying part 18. The degradation time of the fixing part 30 is preferably equal to or longer than the degradation time of the porous structure 20 and shorter than the degradation time of the drug-carrying part 18. The degradation time of the fixing part 30 is preferably within four months, more preferably from one month to four months, and particularly preferably from 1.5 months to four months. Within this degradation time, with the porous structure 20 firmly fixed to the stent 10 via the fixing part 30, the porous structure 20 can suppress the scattering of plaque and thrombus during placement of the indwelling device 100, and an endothelial cell layer can be sufficiently formed on the indwelling device 100 (stent 10).

[0112] The degradation time of the drug-carrying portion 18 can be appropriately selected depending on the target disease and the implantation site. The time required for tissue damage caused by implanting the stent 10 to heal is typically 3 to 4 months. Therefore, the degradation time of the drug-carrying portion 18 is preferably 4 months or longer, more preferably 4 months to 22 months, and particularly preferably 4 months to 12 months. Such a degradation time allows for a sufficient formation of an endothelial cell layer on the stent 10 while more effectively preventing or suppressing inflammation and other issues at the contact site during the implantation period. Furthermore, if the drug-carrying portion 18 further contains another drug that can be used to treat the target, it is possible to effectively suppress or prevent inflammatory reactions induced by the porous structure 20 and simultaneously perform other necessary treatments.

[0113] Here, the degradation time of the fixing part 30, the degradation time of the drug carrying part 18, and the degradation time of the porous structure 20 can be controlled by the type of second biodegradable polymer constituting the fixing part 30, the third biodegradable polymer constituting the drug carrying part 18, and the first biodegradable polymer constituting the porous structure 20, respectively. Note that the sizes of the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer have little or no effect on the degradation time (degradation rate, solubility) (in materials that degrade evenly throughout). That is, the degradation time of the second biodegradable polymer is substantially the same as or shorter than the degradation time of the third biodegradable polymer (the degradation time of the second biodegradable polymer≦the degradation time of the third biodegradable polymer). Preferably, the degradation time of the first biodegradable polymer is substantially the same as or shorter than the degradation time of the third biodegradable polymer (degradation time of the first biodegradable polymer≦degradation time of the third biodegradable polymer). Preferably, the degradation time of the first biodegradable polymer is substantially the same as or shorter than the degradation time of the second biodegradable polymer (degradation time of the first biodegradable polymer≦degradation time of the second biodegradable polymer). A more preferred embodiment is the same as above, except that the porous structure 20 is read as the first biodegradable polymer, the fixing part 30 is read as the second biodegradable polymer, and the drug carrying part 18 is read as the third biodegradable polymer.

[0114] The biodegradable polymers that can be used as the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are not particularly limited and are appropriately selected from known biodegradable polymers according to the degradation time described in detail below.

[0115] Examples of such biodegradable polymers that can be used include known biodegradable polymers such as those described in JP-A Nos. 2011-528275, 2008-514719, WO 2008 / 1952, and 2004-509205. Specific examples include: (1) polymers selected from the group consisting of aliphatic polyesters, polyesters, polyanhydrides, polyorthoesters, polycarbonates, polyphosphazenes, polyphosphate esters, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose; and (2) copolymers composed of two or more types of monomers constituting the above-mentioned (1). The aliphatic polyester is not particularly limited, and examples thereof include polylactic acids (PLA) such as poly-L-lactic acid (PLLA), poly-D-lactic acid (PDLA), and poly-DL-lactic acid (PDLLA), polyglycolic acid (PGA), polyhydroxybutyric acid, polyhydroxyvaleric acid, polyhydroxypentanoic acid, polyhydroxyhexanoic acid, polyhydroxyheptanoic acid, poly(ε-caprolactone) (PCL), polytrimethylene carbonate, poly2,2-dimethyltrimethylene carbonate, polydioxanone, polybutyrolactone, polyvalerolactone, polymalic acid, polyethylene adipate, polyethylene succinate, polybutylene adipate, and polybutylene succinate. The polycarbonate is not particularly limited, and examples thereof include tyrosine-derived polycarbonate (Tyrosine-polycarbonate).

[0116] Alternatively, the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer may be copolymers obtained by arbitrarily copolymerizing the monomers that constitute the polymers. Here, the copolymer is not particularly limited. Specifically, polyglycolic acid-polylactic acid copolymers (PGA-PLA) such as polyglycolic acid-poly-L-lactic acid copolymer (PGA-PLLA), polyglycolic acid-poly-D-lactic acid copolymer (PGA-PDLA), polyglycolic acid-poly-DL-lactic acid copolymer (PGA-PDLLA), polyglycolic acid-polycaprolactone copolymers such as polyglycolic acid-polycaprolactone copolymer (PGA-PCL), poly-L-lactic acid-poly(ε-caprolactone) copolymer (PLLA-PCL), poly-D-lactic acid-poly(ε-caprolactone) copolymer (PDLA-PCL), poly-DL-lactic acid-poly(ε-caprolactone) copolymer (PDLLA-PCL), polylactic acid-polycaprolactone copolymers such as poly-L-lactic acid-polytrimethylene carbonate copolymer (PLLA-PTMC (TMC=trimethylene carbonate) polylactic acid-poly(2,2,-dimethyltrimethylene carbonate) copolymer (PLLA-PTMC) such as poly-D-lactic acid-polytrimethylene carbonate copolymer (PDLA-PTMC) and poly-DL-lactic acid-polytrimethylene carbonate copolymer (PDLLA-PTMC); polylactic acid-poly(2,2,-dimethyltrimethylene carbonate) copolymer (PLLA-PDTC) such as poly-L-lactic acid-poly(2,2,-dimethyltrimethylene carbonate) copolymer (PDLA-PDTC) and poly-DL-lactic acid-poly(2,2,-dimethyltrimethylene carbonate) copolymer (PDLLA-PDTC);-dimethyltrimethylene carbonate) copolymer (PLA-PDTC), poly(lactide-co-glycolide) (PLGA), polyanhydrides, polyorthoesters, poly(N-(2-hydroxypropyl)methacrylamide), poly-DL-lactic acid-poly(dl-lactide), poly-L-lactic acid-poly(l-lactide), polyglycolic acid-polyglycolide, PDO-poly(dioxanone), polyglycolic acid-polytrimethylene carbonate-poly(glycolide-co-trimethylene carbonate) ), polyglycolic acid-poly-L-lactic acid-poly(l-lactide-co-glycolide), polyglycolic acid-poly-DL-lactic acid-poly(dl-lactide-co-glycolide), poly-L-lactic acid-poly-DL-lactic acid-poly(l-lactide-co-dl-lactide), and PDO-polyglycolic acid-polytrimethylene carbonate-poly(glycolide-co-trimethylene carbonate-co-dioxanone), PAE (Polyanhydride esters)-Salicylate in which salicylic acid has been chemically introduced into the polymer main chain (for example, a polymer in which salicylic acid is bound to both ends of polylactide anhydride or polyadipic acid).

[0117] The above polymers and copolymers may be used alone or in combination of two or more types, or in combination of one or more polymers and one or more copolymers. Furthermore, the above polymers and copolymers may be synthesized or commercially available. The synthesis method is not particularly limited, and known methods can be used in the same manner or with appropriate modifications. For example, polylactic acid (PLA), polyglycolic acid (PGA), or lactic acid-glycolic acid copolymer (PLGA) can be obtained by dehydration polycondensation of L-lactic acid, D-lactic acid, or glycolic acid, whichever has the required structure. Alternatively, they can be obtained by ring-opening polymerization of lactide, a cyclic dimer of lactic acid, or glycolide, a cyclic dimer of glycolic acid, which has the required structure. Lactides include L-lactide, which is a cyclic dimer of L-lactic acid, D-lactide, which is a cyclic dimer of D-lactic acid, meso-lactide, which is a cyclic dimer of D-lactic acid and L-lactic acid, and DL-lactide, which is a racemic mixture of D-lactide and L-lactide. Any of these lactides can be used in the present disclosure.

[0118] The weight-average molecular weight of the biodegradable polymer is not particularly limited and can be appropriately selected depending on the desired degradation time (biodegradation rate). Specifically, the weight-average molecular weight (Mw) of the biodegradable polymer is preferably 10,000 or more, more preferably 50,000 to 1,000,000, and even more preferably 100,000 to 500,000. The number-average molecular weight (Mn) of the biodegradable polymer is preferably 5,000 or more, more preferably 20,000 to 800,000, and even more preferably 30,000 to 200,000. Methods for measuring molecular weight (weight-average molecular weight, number-average molecular weight) include gel permeation chromatography (GPC), light scattering, viscosity measurement, and mass spectrometry (TOFMASS, etc.). In this specification, the weight-average molecular weight is a value measured by GPC using polystyrene as a standard.

[0119] The first biodegradable polymer constituting the porous structure 20 can be selected from the biodegradable polymers described above. The porous structure 20, together with the stent 10, preferably exerts tensile strength to expand the biological lumen in which it is placed, and maintains that tensile strength throughout the placement period. The porous structure 20 is preferably a bulk erosion type in which the entire structure is eroded (the entire material decomposes evenly). This configuration can more effectively suppress and prevent peripheral embolism caused by breakage or detachment of the components (e.g., knitted threads) constituting the porous structure 20.

[0120] Specifically, the first biodegradable polymer is preferably a homopolymer of one monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or a copolymer of two or more monomers. The first biodegradable polymer is more preferably a homopolymer of one monomer selected from the group consisting of lactic acid, caprolactone, and glycolic acid, or a copolymer of two or more monomers. It is even more preferable that the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer. From the viewpoint of a relatively fast biodegradation rate (short degradation time), the first biodegradable polymer may be polyglycolic acid, a polyglycolic acid-polylactic acid copolymer containing glycolic acid in an amount of more than 10 mol% and less than 100 mol% (preferably 25 mol% or more and 95 mol% or less, more preferably more than 50 mol% and 95 mol% or less) of the total monomers (polyglycolic acid-poly-L-lactic acid copolymer, polyglycolic acid-poly-D-lactic acid copolymer, polyglycolic acid-poly-DL-lactic acid copolymer, preferably polyglycolic acid-poly-L-lactic acid copolymer, polyglycolic acid-poly-D-lactic acid copolymer), or a polymer containing caprolactone in an amount of 4 mol% or more of the total monomers. It is particularly preferred that the first biodegradable polymer is at least one selected from the group consisting of a polyglycolic acid-polycaprolactone copolymer containing the above (preferably 5 mol% to 40 mol%, more preferably 10 mol% to 30 mol%), and a polylactic acid-polycaprolactone copolymer containing caprolactone in an amount of 5 mol% to 40 mol% (preferably 8 mol% to 20 mol%) of the total monomers (polyε-caprolactone-poly-L-lactic acid copolymer, polyε-caprolactone-poly-D-lactic acid copolymer, polyε-caprolactone-poly-DL-lactic acid copolymer, and particularly polyε-caprolactone-poly-DL-lactic acid copolymer). From the standpoints of ease of molding, strength, etc., the first biodegradable polymer is most preferably polyglycolic acid.

[0121] The weight-average molecular weight of the first biodegradable polymer is not particularly limited and may be appropriately selected depending on the desired degradation time (biodegradation rate). Specifically, the weight-average molecular weight (Mw) of the first biodegradable polymer is preferably 100,000 or more and 300,000 or less, and more preferably 120,000 or more and 180,000 or less. The number-average molecular weight (Mn) of the first biodegradable polymer is preferably 20,000 to 150,000, and even more preferably 55,000 to 85,000.

[0122] The crystallinity of the first biodegradable polymer is, for example, 0% or more and 40% or less, more preferably 0% or 20% or more and 40% or less, and even more preferably 20% or more and 40% or less.

[0123] The crystallinity can be measured, for example, as follows.

[0124] In accordance with JIS-K7122, approximately 10 mg of a sample is heated from 20°C to 250°C at a heating rate of 10°C / min and a nitrogen gas flow rate of 20 ml / min using a differential scanning calorimeter (Diamond DSC manufactured by PerkinElmer). The heat of crystallization (ΔHc) [J / g] is determined from the area of ​​the exothermic crystallization peak during heating in the DSC curve drawn, and the heat of crystal fusion (ΔHm) [J / g] is determined from the area of ​​the endothermic crystal melting peak, and the degree of crystallinity is calculated using the following formula.

[0125] Crystallinity = (ΔHm - ΔHc) x 100 / ΔHf [%] Here, ΔHf refers to the heat of fusion for complete crystallization, and is the heat of crystalline fusion of each polymer that is 100% crystallized. For example, in the case of homopolymers, the heat of crystalline fusion (ΔHf) of polyglycolic acid is 206.0 J / g, the heat of crystalline fusion (ΔHf) of polylactic acid is 93.7 J / g, and the heat of crystalline fusion (ΔHf) of polycaprolactone is 136.1 J / g. In addition, in the case of a copolymer composed of two different polymers, the heat of crystalline fusion (ΔHf) can be calculated from the molar ratio of each constituent polymer using the following formula: Heat of crystalline fusion (ΔHf) = {(ΔHf １ ×M １ ) + (ΔHf ２ ×M ２)} / 100 where ΔHf １ is the heat of crystalline fusion of the first constituent polymer, ΔHf ２ is the heat of crystalline fusion of the second constituent polymer, M １ is the molar ratio of the first constituent polymer, M ２ indicates the molar ratio of the second constituent polymer.

[0126] The second biodegradable polymer constituting the fixing portion 30 can be selected from the above biodegradable polymers. The fixing portion 30 connects the stent 10 and the porous structure 20. The fixing portion 30 is preferably a bulk erosion type that is eroded entirely (the entire material decomposes evenly).

[0127] Specifically, the second biodegradable polymer is preferably a homopolymer of one monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or a copolymer of two or more monomers. The second biodegradable polymer is more preferably a homopolymer of one monomer selected from the group consisting of lactic acid, caprolactone, and glycolic acid, or a copolymer of two or more monomers. It is even more preferable that the second biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer. Considering the preferred degradation time of the fixing part, the second biodegradable polymer may be polyglycolic acid, a polyglycolic acid-polylactic acid copolymer containing glycolic acid in an amount of more than 10 mol% and less than 100 mol% (preferably 25 mol% or more and 95 mol% or less, more preferably more than 50 mol% and 95 mol% or less) of the total monomers (polyglycolic acid-poly-L-lactic acid copolymer, polyglycolic acid-poly-D-lactic acid copolymer, polyglycolic acid-poly-DL-lactic acid copolymer, preferably polyglycolic acid-poly-L-lactic acid copolymer, polyglycolic acid-poly-D-lactic acid copolymer), or a polymer containing caprolactone in an amount of 4 mol% or more of the total monomers (preferably The second biodegradable polymer is particularly preferably at least one selected from the group consisting of polyglycolic acid-polycaprolactone copolymers containing caprolactone at a concentration of from 5 mol% to 40 mol%, and more preferably from 10 mol% to 30 mol%, and polylactic acid-polycaprolactone copolymers containing caprolactone at a concentration of from 5 mol% to 40 mol% (preferably from 8 mol% to 20 mol%) of the total monomers (polyε-caprolactone-poly-L-lactic acid copolymer, polyε-caprolactone-poly-D-lactic acid copolymer, polyε-caprolactone-poly-DL-lactic acid copolymer, and particularly polyε-caprolactone-poly-DL-lactic acid copolymer). The second biodegradable polymer is most preferably a poly-DL-lactic acid-polycaprolactone copolymer containing caprolactone at 10 mol% of the total monomers.

[0128] The weight-average molecular weight of the second biodegradable polymer is not particularly limited and may be appropriately selected depending on the desired degradation time (biodegradation rate). Specifically, the weight-average molecular weight (Mw) of the second biodegradable polymer is preferably 100,000 or more and 300,000 or less, and more preferably 120,000 or more and 180,000 or less. The number-average molecular weight (Mn) of the second biodegradable polymer is preferably 20,000 to 150,000, and even more preferably 55,000 to 85,000.

[0129] The crystallinity of the second biodegradable polymer is, for example, 0% or more and 40% or less, more preferably 0% or 20% or more and 40% or less, and even more preferably 0%.

[0130] The third biodegradable polymer constituting the drug-carrying portion 18 can be selected from the above-mentioned biodegradable polymers. The drug-carrying portion 18 is preferably a bulk erosion type that erodes entirely (the entire material decomposes evenly).

[0131] Specifically, the third biodegradable polymer is preferably a homopolymer of one monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or a copolymer of two or more monomers. The third biodegradable polymer is more preferably a homopolymer of one monomer selected from the group consisting of lactic acid and caprolactone, or a copolymer of two or more monomers. The third biodegradable polymer is more preferably at least one selected from the group consisting of polylactic acid-polycaprolactone copolymer and polylactic acid. Considering the preferred degradation time of the drug-carrying portion 18, it is particularly preferred that the third biodegradable polymer be at least one selected from the group consisting of polylactic acid (poly-L-lactic acid, poly-D-lactic acid, poly-DL-lactic acid, preferably poly-DL-lactic acid) and polylactic acid-polycaprolactone copolymers (poly-ε-caprolactone-poly-L-lactic acid copolymer, poly-ε-caprolactone-poly-D-lactic acid copolymer, poly-ε-caprolactone-poly-DL-lactic acid copolymer, particularly poly-ε-caprolactone-poly-DL-lactic acid copolymer) containing caprolactone in an amount of 5 mol% to 40 mol% (preferably 8 mol% to 20 mol%) of the total monomers. The third biodegradable polymer is most preferably a poly-DL-lactic acid-polycaprolactone copolymer containing caprolactone in an amount of 10 mol% of the total monomers.

[0132] In one embodiment of the present invention, the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer; the second biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer; and the third biodegradable polymer is at least one selected from the group consisting of polylactic acid-polycaprolactone copolymer and polylactic acid.

[0133] In one embodiment of the present invention, the first biodegradable polymer is selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymers (polyglycolic acid-poly-L-lactic acid copolymers, polyglycolic acid-poly-D-lactic acid copolymers, polyglycolic acid-poly-DL-lactic acid copolymers, preferably polyglycolic acid-poly-L-lactic acid copolymers and polyglycolic acid-poly-D-lactic acid copolymers) containing glycolic acid in an amount of more than 10 mol% and less than 100 mol% (preferably 25 mol% or more and 95 mol% or less, more preferably more than 50 mol% and 95 mol% or less) of all monomers), and caprolactone in an amount of 4 mol% or more of all monomers. and polylactic acid-polycaprolactone copolymers containing caprolactone in an amount of 5 mol% to 40 mol% (preferably 8 mol% to 20 mol%) of the total monomers (polyε-caprolactone-poly-L-lactic acid copolymer, polyε-caprolactone-poly-D-lactic acid copolymer, polyε-caprolactone-poly-DL-lactic acid copolymer, particularly polyε-caprolactone-poly-DL-lactic acid copolymer). the second biodegradable polymer is one of polyglycolic acid, polyglycolic acid-polylactic acid copolymers (polyglycolic acid-poly-L-lactic acid copolymers, polyglycolic acid-poly-D-lactic acid copolymers, polyglycolic acid-poly-DL-lactic acid copolymers, preferably polyglycolic acid-poly-L-lactic acid copolymers, polyglycolic acid-poly-D-lactic acid copolymers) containing glycolic acid in an amount of more than 10 mol% and less than 100 mol% (preferably 25 mol% or more and 95 mol% or less, more preferably more than 50 mol% and 95 mol% or less) of the total monomers, or caprolactone in an amount of 4 mol% or more (preferably and at least one selected from the group consisting of polyglycolic acid-polycaprolactone copolymers containing caprolactone in an amount of 5 mol% or more and 40 mol% or less, more preferably 10 mol% or more and 30 mol% or less), and polylactic acid-polycaprolactone copolymers containing caprolactone in an amount of 5 mol% or more and 40 mol% or less (preferably 8 mol% or more and 20 mol% or less) of the total monomers (polyε-caprolactone-poly-L-lactic acid copolymer, polyε-caprolactone-poly-D-lactic acid copolymer, polyε-caprolactone-poly-DL-lactic acid copolymer, in particular polyε-caprolactone-poly-DL-lactic acid copolymer);The third biodegradable polymer is at least one selected from the group consisting of polylactic acid (poly-L-lactic acid, poly-D-lactic acid, poly-DL-lactic acid, preferably poly-DL-lactic acid) and polylactic acid-polycaprolactone copolymers containing caprolactone in an amount of 5 mol % to 40 mol % (preferably 8 mol % to 20 mol %) of the total monomers (poly-ε-caprolactone-poly-L-lactic acid copolymer, poly-ε-caprolactone-poly-D-lactic acid copolymer, poly-ε-caprolactone-poly-DL-lactic acid copolymer, particularly poly-ε-caprolactone-poly-DL-lactic acid copolymer);

[0134] In one embodiment of the present invention, the first biodegradable polymer is polyglycolic acid; the second biodegradable polymer is poly(DL-lactic acid)-polycaprolactone copolymer containing 10 mol % of caprolactone based on the total monomers; and the third biodegradable polymer is poly(DL-lactic acid)-polycaprolactone copolymer containing 10 mol % of caprolactone based on the total monomers.

[0135] The weight-average molecular weight of the third biodegradable polymer is not particularly limited and may be appropriately selected depending on the desired degradation time (biodegradation rate). Specifically, the weight-average molecular weight (Mw) of the third biodegradable polymer is preferably 50,000 or more and 250,000 or less, and more preferably 100,000 or more and 120,000 or less. The number-average molecular weight (Mn) of the third biodegradable polymer is preferably 20,000 to 150,000, and even more preferably 55,000 to 85,000.

[0136] The crystallinity of the third biodegradable polymer is, for example, 0% or more and 40% or less, more preferably 0% or 20% or more and 40% or less, and even more preferably 0%.

[0137] That is, in one embodiment of the present invention, the weight average molecular weight of the first biodegradable polymer is 100,000 or more and 300,000 or less, the weight average molecular weight of the second biodegradable polymer is 100,000 or more and 300,000 or less, and the weight average molecular weight of the third biodegradable polymer is 50,000 or more and 250,000 or less.

[0138] In one embodiment of the present invention, the weight average molecular weight of the first biodegradable polymer is 120,000 or more and 180,000 or less, the weight average molecular weight of the second biodegradable polymer is 120,000 or more and 180,000 or less, and the weight average molecular weight of the third biodegradable polymer is 100,000 or more and 120,000 or less.

[0139] In one embodiment of the present invention, the number average molecular weight of the first biodegradable polymer is 20,000 to 150,000, the number average molecular weight of the second biodegradable polymer is 20,000 to 150,000, and the number average molecular weight of the third biodegradable polymer is 20,000 to 150,000.

[0140] In one embodiment of the present invention, the number average molecular weight of the first biodegradable polymer is 55,000 to 85,000, the number average molecular weight of the second biodegradable polymer is 55,000 to 85,000, and the number average molecular weight of the third biodegradable polymer is 55,000 to 85,000.

[0141] The degradation time of the drug-carrying portion 18, the fixing portion 30, and (if necessary) the porous structure 20 can be adjusted by appropriately selecting the types of materials described above. Alternatively or in addition to the above, the degradation time of the biodegradable polymer may be adjusted by controlling the composition (e.g., glass transition temperature), molecular weight (e.g., in the case of a porous structure, the length of the constituent threads), and crystallinity (e.g., in the case of a porous structure, the spinning conditions, or the presence or absence of annealing) of the biodegradable polymer (e.g., a low crystallinity shortens the degradation time; for example, controlling the crystallinity to 0% to 40%), appropriately selecting the presence or absence of terminal treatment (e.g., terminal treatment by esterification lengthens the degradation time), or using an additive. Among these, methods of controlling the molecular weight, composition (glass transition temperature), or crystallinity of the biodegradable polymer are preferred from the standpoint of ease of control of degradation time. Furthermore, for the drug-carrying portion 18, methods for controlling its degradation time include controlling the molecular weight, composition, or crystallinity of the third biodegradable polymer (e.g., a high degree of crystallinity increases the degradation time, e.g., controlling the crystallinity to over 40%), appropriately selecting whether or not to perform end treatment (e.g., performing end treatment by esterification increases the degradation time), controlling the mixing ratio and mixing method of the third biodegradable polymer and the drug, using additives, and controlling the shape of the drug. Among these, methods for controlling the molecular weight, composition, or crystallinity of the third biodegradable polymer and controlling the mixing ratio and mixing method of the third biodegradable polymer and the drug are preferred from the standpoint of ease of control of the degradation time of the drug-carrying portion 18 (third biodegradable polymer). Typically, the biodegradation rate slows as the molecular weight (weight-average molecular weight) of the biodegradable polymer increases. For this reason, a method for appropriately adjusting the molecular weight (weight-average molecular weight) of the first, second, and third biodegradable polymers can be used.

[0142] Alternatively, the fixing part 30 or the porous structure 20 may contain a biodegradable polymer that has been irradiated with an electron beam in advance. Generally, when a (co)polymer is irradiated with an electron beam, bonds within the (co)polymer are more likely to be broken, increasing the rate of biodegradation. Therefore, even when biodegradable polymers of the same composition are used, the degradation time can be adjusted by irradiating the biodegradable polymer used in the fixing part 30 or the porous structure 20 with an electron beam in advance.

[0143] The first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are preferably selected from combinations 1 to 20 shown in the table below. The combination of the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer is more preferably combination 13 shown in the table below. Note that although only the third biodegradable polymer is exemplified in the table below, the drug-carrying portion 18 also contains a drug in addition to the third biodegradable polymer. In the table below, when the drug-carrying portion 18 contains poly D,L-lactic acid-polycaprolactone (90 / 10) copolymer or poly D,L-lactic acid as the third biodegradable polymer, the drug-carrying portion 18 contains a limus drug (preferably sirolimus) as the drug. In this case, the drug content (in terms of solid content) is preferably 50 to 60% by mass, more preferably 50 to 55% by mass, and particularly preferably 50% by mass (drug:third biodegradable polymer=50:50 (mass ratio)) relative to the drug-carrying portion 18. An indwelling device having this combination can be suitably used for heart diseases such as acute coronary syndrome (ACS), acute myocardial infarction (AMI), and ST-elevation myocardial infarction (STEMI), in particular acute myocardial infarction.

[0144]

[0145]

[0146]

[0147]

[0148]

[0149]

[0150]

[0151] (The constituent ratios of the copolymers in the table are molar ratios.) The size of the porous structure 20 is not particularly limited and is set within a range that does not significantly impair the performance of the stent 10, such as its reachability (deliverability) to the biological lumen and its lesions where it is to be placed, and its irritation to the blood vessel wall. Preferably, the porous structure 20 is arranged so as to cover the entire outer peripheral surface of the stent 10.

[0152] The thickness of the porous structure 20 (synonymous with the outer diameter of the framework 24b) is not particularly limited and is set within a range that does not significantly impair the performance of the stent 10, such as delivery to a biological lumen and its lesions, and irritation to the blood vessel wall. Specifically, the thickness of the porous structure 20 (the radial thickness in the cross-sectional views perpendicular to the axial direction shown in Figures 7 to 9) is not particularly limited and is set within a range that does not significantly impair the performance of the stent 10, such as delivery to a biological lumen and its lesions, and irritation to the blood vessel wall. For example, the thickness of the porous structure 20 is preferably 1 μm to 100 μm, and more preferably 5 μm to 50 μm. This thickness can more effectively suppress and prevent peripheral embolism associated with the dispersal of plaque or thrombus during or after the placement of the stent 10. Regarding the function related to the thickness of the porous structure 20, a thinner thickness is preferable within a range that maintains mechanical strength. A thinner porous structure 20 is advantageous in terms of improving foldability and preventing the device profile from becoming too large, thereby improving passage through a lesion. In other words, an excessively thick porous structure 20 is disadvantageous in terms of foldability and device profile, and also reduces the inner diameter (expanded diameter) of the stent 10 after placement in a lesion, thereby reducing the effectiveness of improving blood flow. This is thought to result in increased susceptibility to thrombus adhesion. The radial thickness of the stent 10 (the radial thickness in the cross-sectional views perpendicular to the axial direction shown in Figures 7 to 9) can be configured to be greater than the thickness of the porous structure 20. When the thickness of the porous structure 20 is configured to the dimensions exemplified above, the thickness of the stent 10 can be configured to be, for example, 60 μm to 120 μm.

[0153] As for the method of producing the porous structure 20 and the method of coating the stent 10 with the porous structure 20, the methods described in, for example, WO 2008 / 062414 can be applied in the same manner or with appropriate modifications.

[0154] Furthermore, as a method for fixing the porous structure 20 and the stent 10 via the fixing part 30, for example, a method can be used in which the porous structure 20, the stent 10, and the fixing part 30 are prepared, the fixing part 30 and the porous structure 20 are sequentially placed at predetermined positions on the stent 10, and then the fixing part 30 and the porous structure 20 are integrated by applying heat.

[0155] In the in-vivo indwelling device 10, the drug-carrying portion 18 contains a drug in addition to the third biodegradable polymer. The drug contained in the drug-carrying portion 18 is not particularly limited and can be appropriately selected depending on the desired application. Considering the inflammation induced by the porous structure 18 and the fixing portion 30, the drug preferably contains an anti-inflammatory agent or an immunosuppressant. The anti-inflammatory agent is not particularly limited, and known anti-inflammatory agents can be used. The anti-inflammatory agent may be a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, or a combination thereof. Examples of anti-inflammatory agents include alclofenac, alclometasone dipropionate, algestone acetonide, alpha amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anilolac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelain, broperamol, budesonide, and carprofen. , cycloprofen, synthasone, criprofen, clobetasol propionate, clobetasone butyrate, clopirac, cloticasone propionate, cormetasone acetate, cortodoxone, deflazacort, desonide, desoximetasone, dexamethasone, dexamethasone dipropionate, diclofenac potassium, diclofenac sodium, diflorasone diacetate, diflumidone sodium, diflunisal, difluprednate, dif Talon, dimethyl sulfoxide, drocinonide, endrizone, enlimomab, enolicam sodium, epirizole, etodolac, etofenamate, felbinac, fenamol, fenbufen, fenclofenac, fenclorac, fendosal, fenpiparone, fentiazac, flavazalon, fluazacort, flufenamic acid, flumizole, flunisolide acetate, flunixin, flunixin meglumine, fluocortin butyl, fluorometholone acetate, fluquazone, flurbiprofen, fluretofen, fluticasone propionate, furaprofen, flobufen, halcinonide, halobetasol propionate, halopredone acetate, ibufenac, ibuprofen, ibuprofen aluminum, ibuprofen piconol, ilonidap, indomethacin, indomethacin sodium, indoprofen, indoxol,Intrazol, isoflupredone acetate, isoxepac, isoxicam, ketoprofen, lofemizole hydrochloride, romoxicam, loteprednol etabonate, meclofenamate sodium, meclofenamic acid, mechlorisone dibutyrate, mefenamic acid, mesalamine, meseclazone, prednisolone, methylprednisolone suleptanate, momiflumate, nabumetone, naproxen, naproxen sodium, naproxol, nimazone, olsalazine sodium, orgotein, orpanoxin, oxaprozin, oxyphenbutazone, paranyline hydrochloride, pentosan polysulfate sodium, phenbutazone sodium glycerate, pirfenidone, piroxicam, piroxicam cinnamate, piroxicam olamine, pirprofen, prednazate, Priferon Examples of the anti-inflammatory agent include prodolic acid, proquazone, proxazole, proxazole citrate, rimexolone, romazarit, sarcorex, salnacedin, salsalate, sanguinarium chloride, seclazone, selmetacin, sudoxicam, sulindac, suprofen, talmetacin, talniflumate, talosalate, tebufelone, tenidap, tenidap sodium, tenoxicam, tesicam, tesimide, tetridamine, thiopinac, tixocortol pivalate, tolmetin, tolmetin sodium, triclonide, triflumidate, zidometacin, zomepirac sodium, aspirin (acetylsalicylic acid), salicylic acid, corticosteroids, glucocorticoids, tacrolimus, pimecollimus, prodrugs thereof, and co-drugs thereof. The above anti-inflammatory agents may be used alone or in combination of two or more.

[0156] The immunosuppressant is also not particularly limited, and known immunosuppressants can be used. Examples include sirolimus, everolimus, biolimus A9, pimecrolimus, zotarolimus, sirolimus derivatives such as ABT-578, biolimus (e.g., Biolimus A9 (registered trademark)), tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, and gusperimus. The above immunosuppressants may be used alone or in combination with two or more. Furthermore, the above immunosuppressants may be used in combination with an anti-inflammatory agent.

[0157] Here, the amount of drug contained in the drug-carrying portion 18 is not particularly limited as long as it is an amount that produces the desired medicinal effect, but from the viewpoint of further exerting an anti-inflammatory effect, it is preferable to contain a large amount of drug. Specifically, the drug content in the drug-carrying portion 18 is preferably 30% by mass or more and 60% by mass or less, more preferably 45% by mass or more and 50% by mass or less, and particularly preferably 50% by mass, relative to the total amount (100% by mass) of the third biodegradable polymer and the drug. With this composition, an appropriate amount of drug can be effectively sustained-released for a predetermined period of time.

[0158] Furthermore, the drug-carrying portion 18 may contain other drugs in addition to the anti-inflammatory drug. Preferably, the drug-carrying portion 18 is composed only of the third biodegradable polymer and the drug. More preferably, the drug-carrying portion 18 is composed only of the third biodegradable polymer and at least one of the anti-inflammatory drug and the immunosuppressant. Particularly preferably, the drug-carrying portion 18 is composed only of the third biodegradable polymer and the immunosuppressant.

[0159] In the case where the drug-carrying portion 18 further contains another drug, the other drug is not particularly limited, but is preferably a drug that suppresses stenosis or occlusion of the vascular system that may occur when the living body indwelling device 100 is placed in the lesion. Specific examples include anticancer drugs such as paclitaxel, docetaxel, vinblastine, vindesine, irinotecan, and pirarubicin; antibiotics such as mitomycin, adriamycin, doxorubicin, actinomycin, daunorubicin, idarubicin, pirarubicin, aclarubicin, epirubicin, and zinostatin stimalamer; antithrombotic drugs such as aspirin and ticlopidine; HMG-CoA reductase inhibitors such as cerivastatin, cerivastatin sodium, atorvastatin, pitavastatin, fluvastatin, fluvastatin sodium, simvastatin, and lovastatin; quinapril, trandolapril, and temocapril. Examples of other drugs include ACE inhibitors such as benzodiazepine, delapril, enalapril maleate, and captopril; calcium channel blockers such as hifedipine, nilvadipine, benidipine, and nisoldipine; antihyperlipidemic drugs such as probucol; integrin inhibitors such as AJM300; antiallergic agents such as tranilast; antioxidants such as α-tocopherol, catechin, dibutylhydroxytoluene, and butylhydroxyanisole; GPIIbIIIa antagonists such as abciximab; retinoids such as all-trans retinoic acid; lipid-improving drugs such as eicosapentaenoic acid; and antiplatelet drugs such as ticlopidine, cilostazol (500), and clopidogrel. These drugs are preferred because they can control the behavior of cells in the affected tissue and treat the affected area. The other drugs may be used alone or in combination.

[0160] The method for forming the drug-carrying portion 18 is not particularly limited, and examples that can be used include a method of mixing a third biodegradable polymer and a drug, and, if necessary, at least one of a solvent and other drugs, to obtain a mixture, and applying this mixture to a predetermined site on the stent 10 (the method for producing the indwelling device 100 of the first and second embodiments described above), a method of mixing a third biodegradable polymer and a drug, and, if necessary, at least one of a solvent and other drugs, to obtain a mixture, and using this mixture to mold the stent 10 (the method for producing the indwelling device 100 of the third embodiment described above), and the like.

[0161] As described above, the indwelling device 100 according to this embodiment comprises the expandable tubular stent 10, the porous structure 20 made of a first biodegradable polymer arranged to cover the stent 10, and the fixing part 30 made of a second biodegradable polymer that fixes at least a portion of the porous structure 20 to the stent 10, the stent 10 having a drug-carrying part 18 containing a third biodegradable polymer and a drug, the degradation time of the fixing part 30 being substantially the same as or shorter than the degradation time of the drug-carrying part 18. Preferably, the degradation time of the porous structure 20 is substantially the same as or shorter than the degradation time of the drug-carrying part 18. More preferably, the degradation time of the porous structure 20 is substantially the same as or shorter than the degradation time of the fixing part 30. According to the implantable device 100 configured as described above, after a certain period of time has passed since implantation, the fixing part 30 (and further the porous structure 20) decomposes and disappears, and the release of the drug from the stent 10 continues until the fixing part 30 (and further the porous structure 20) decomposes and disappears. Therefore, the implantable device 100 can effectively suppress the onset of inflammation caused by the fixing part 30 (and further the porous structure 20) made of a biodegradable polymer, while preventing the scattering of plaque and thrombus when the stent 10 is expanded.

[0162] This application is based on Japanese Patent Application No. 2024-052913, filed on March 28, 2024, the disclosure of which is hereby incorporated by reference in its entirety.

Claims

1. A living body implant comprising an expandable cylindrical stent, a porous structure made of a first biodegradable polymer arranged to cover the stent, and a fixing portion made of a second biodegradable polymer that fixes at least a portion of the porous structure to the stent, wherein the stent has a drug-carrying portion containing a third biodegradable polymer and a drug, and the degradation time of the fixing portion is substantially the same as or shorter than the degradation time of the drug-carrying portion.

2. The indwelling device according to claim 1, wherein the decomposition time of the porous structure is substantially the same as or shorter than the decomposition time of the drug-carrying portion.

3. The indwelling device according to claim 1, wherein the decomposition time of the porous structure is substantially the same as or shorter than the decomposition time of the fixing part.

4. The indwelling device according to claim 1, wherein the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer; the second biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polyglycolic acid-polylactic acid copolymer, polyglycolic acid-polycaprolactone copolymer, and polylactic acid-polycaprolactone copolymer; and the third biodegradable polymer is at least one selected from the group consisting of polylactic acid-polycaprolactone copolymer and polylactic acid.

5. The indwelling device according to claim 1, wherein the weight average molecular weight of the first biodegradable polymer is 120,000 or more and 180,000 or less, the weight average molecular weight of the second biodegradable polymer is 120,000 or more and 180,000 or less, and the weight average molecular weight of the third biodegradable polymer is 100,000 or more and 120,000 or less.

6. The indwelling device according to claim 1, wherein the tensile strength of the porous structure is maintained for a period of 7 days or more.

7. The indwelling device according to claim 1, wherein the decomposition time of the porous structure is within four months.

8. The indwelling device according to claim 1, wherein the decomposition time of the fixing part is within four months.

9. The indwelling device according to claim 1, wherein the decomposition time of the drug-carrying portion is 4 months or more.

10. The indwelling device according to claim 1, wherein the decomposition time of the fixing part is substantially the same as the decomposition time of the drug-carrying part, and the decomposition time of the porous structure is shorter than the decomposition time of the drug-carrying part.

11. The indwelling device according to claim 1, wherein the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are selected from combinations 1 to 20 shown in the table below. (The composition ratio of each copolymer in the table is a molar ratio.) 12. The indwelling device according to claim 11, wherein the first biodegradable polymer, the second biodegradable polymer, and the third biodegradable polymer are the combination 13 above.

13. The indwelling device according to claim 1, wherein the stent is made of a non-biodegradable material, and the drug-carrying portion is disposed only on the portion of the surface of the ring that forms the stent that faces the porous structure.

14. The indwelling device according to claim 1, wherein the stent is made of a non-biodegradable material, and the drug-carrying portion is arranged so as to cover the entire surface of the rings that form the stent.

15. The indwelling device according to claim 1, wherein the entire stent is constituted by the drug-carrying portion.

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