Living organisms

Abstract

The present invention provides a biological implant that prevents the scattering of plaque and thrombi during stent expansion by using a porous structure, while also preventing the reduction in delivery efficiency that can occur as a result of providing a porous structure. [Solution] The biological implant 100 comprises an expandable cylindrical stent 10 and a porous structure 20 disposed on the inner circumference side of the stent 10 and configured to expand in accordance with the expansion of the stent 10.

Description

Technical Field

[0001] The present invention relates to a biological implant.

Background Art

[0002] A stent is implanted after being delivered to a lesion in a biological lumen by a stent delivery system in order to treat various diseases caused by stenosis or occlusion of a biological lumen such as a blood vessel, and expands a lesion such as a stenosis or occlusion portion to secure the lumen. It is a medical device.

[0003] For example, Patent Document 1 discloses a stent provided with a cover layer made of a knitted fabric that covers the outer periphery of an expandable stent body in order to prevent peripheral embolism (restenosis, etc.) during stent implantation. In the stent of Patent Document 1, when the stent body expands, the cover layer provided with meshes expands so as to follow the stent body, and it is possible to prevent the scattering of plaques and thrombi when the stent body expands.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, when a cover layer provided with meshes is disposed on the outer peripheral side of the stent body, the cover layer may get caught in the biological lumen when delivering the stent to a lesion or the like in the biological lumen. As a result, there is a risk of reducing the deliverability of the stent.

[0006] The present invention has been made in view of the above problems, and aims to provide a biological implant that prevents the scattering of plaque and thrombi during stent expansion by using a porous structure, while also preventing a decrease in delivery efficiency that may occur as a result of providing a porous structure. [Means for solving the problem]

[0007] The above object of the present invention can be achieved by any one of the following means (1) to (7).

[0008] (1) A cylindrical stent that can be expanded in diameter, A biological implant comprising: a porous structure disposed on the inner circumference side of the stent and configured to expand as the diameter of the stent expands.

[0009] (2) The porous structure is composed of a first biodegradable polymer, The stent has a drug-carrying portion containing a second biodegradable polymer and a drug, The biological implant 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 stent and the porous structure are fixed together, and the fixing portion further includes a third biodegradable polymer material. The fixation portion is located in a part of the stent where the drug-carrying portion is not provided, as described in (2).

[0011] (4) The stent has a plurality of wavy rings forming the outer circumference of a cylindrical shape, and link portions connecting adjacent rings. The aforementioned link portion is not provided with the drug-carrying portion. The fixing portion is located on at least a part of the link portion, and is the biological implant described in (3).

[0012] (5) The biodegradation time of the fixing part is substantially the same as or shorter than the biodegradation time of the drug-carrying part, the bioimplant according to (3) or (4).

[0013] (6) The porous structure has a skeleton part arranged in a network shape, a plurality of void parts partitioned by the skeleton part, and a coating part including a polymer material arranged to cover at least a part of the porous structure, the bioimplant according to any one of (1) to (5). The coating part has uneven parts formed along the surface shape of the porous structure, the bioimplant according to any one of (1) to (5).

[0014] (7) The porous structure has a skeleton part arranged in a network shape, a plurality of void parts partitioned by the skeleton part, and a coating part including a polymer material arranged to cover at least a part of the outer surface of the porous structure, the bioimplant according to any one of (1) to (5). The coating part is arranged only along the skeleton part surrounding the void part and is not arranged at a position corresponding to the void part, the bioimplant according to any one of (1) to (5).

Advantages of the Invention

[0015] According to the present invention, there is provided a bioimplant that can prevent the scattering of plaques and thrombi during the expansion of a stent by a porous structure and can prevent a decrease in delivery performance caused by providing the porous structure.

Brief Description of the Drawings

[0016] [Figure 1] It is a schematic plan view showing a stent delivery system including a bioimplant according to an embodiment. [Figure 2] It is a plan view showing a reduced-diameter state of a bioimplant according to an embodiment. [Figure 3] It is an axial orthogonal cross-sectional view of the biological implant along the arrow 3A-3A shown in FIG. 1. [Figure 4] It is an enlarged view showing a part of the biological implant in the expanded diameter state according to the embodiment. [Figure 5] It is an enlarged view showing an enlarged part of the biological implant in the state shown in FIG. 4. [Figure 6] It is an enlarged view showing a further enlarged part of the biological implant in the state shown in FIG. 5. [Figure 7] It is a schematic cross-sectional view showing a part of the biological implant according to the embodiment. [Figure 8] It is a schematic cross-sectional view showing a part of the biological implant according to the embodiment. [Figure 9] It is a plan view showing the biological implant according to the first modification. [Figure 10] It is an axial orthogonal cross-sectional view showing an enlarged part of the biological implant according to the first modification. [Figure 11] It is a cross-sectional view along the axial direction showing an enlarged part of the biological implant according to the first modification. [Figure 12] It is an axial orthogonal cross-sectional view showing an enlarged part of the biological implant according to the second modification. [Figure 13] It is a cross-sectional view along the axial direction showing an enlarged part of the biological implant according to the second modification.

Mode for Carrying Out the Invention

[0017] 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 the meaning of terms described in the claims. Also, the dimensional ratios in the drawings are exaggerated for convenience of explanation and may be different from the actual ratios.

[0018] (Embodiment) The embodiment will be described with reference to FIGS. 1 to 8.

[0019] FIG. 1 is a diagram showing a stent delivery system 300 including a biological implant 100 according to the embodiment.

[0020] Figures 2 to 8 are diagrams illustrating the biological implant 100, stent 10, and porous structure 20 according to the embodiment. Specifically, Figure 2 is a schematic plan view showing the reduced diameter state of the stent 10 and porous structure 20 according to the embodiment; Figure 3 is a cross-sectional view perpendicular to the axis of the biological implant 100 along the arrow 3A-3A shown in Figure 1 (cross-sectional view perpendicular to the axis when the balloon 220 is expanded); and Figures 4 to 6 are schematic plan views showing the expanded diameter state of the stent 10 according to the embodiment. Figures 7 and 8 are schematic cross-sectional views illustrating the characteristic parts of the biological implant 100 according to the embodiment.

[0021] For the sake of clarity, the following directions are defined in this specification.

[0022] The longitudinal direction in which the stent 10 and the porous structure 20 extend is defined as the "axial direction." The axial direction is the direction from the tip 10A to the base 10B (or from the base 10B to the tip 10A) as shown in Figure 2, and is indicated by arrows X1-X2 in each figure.

[0023] In the stent 10 and the porous structure 20, the side that is introduced into the body is called the "proximal side," and the side opposite the proximal side, on which the operator operates the stent delivery system 300, is called the "proximal side." The "proximal portion" refers to the part that includes a certain range from the proximal (frontmost) end towards the proximal end, and the "proximal end" refers to the part that includes a certain range from the proximal (very proximal) end towards the proximal end. Furthermore, the rotational direction relative to the axial direction is defined as the circumferential direction and is indicated by arrows R1-R2 in the figure.

[0024] In this specification, the inner surface 19a of the stent 10 (or strut) refers to the surface of the stent 10 on which the porous structure 20 is placed (the surface facing the lumen 18). The outer surface 19b of the stent 10 (or strut) refers to the surface of the stent 10 that faces the outside.

[0025] <Stent Delivery System 300> As shown in Figure 1, the biological implant 100 according to this embodiment is positioned on the outer circumference of the expandable and deflated balloon 220 provided by the balloon catheter 200.

[0026] The balloon catheter 200 comprises a long catheter body 210, a balloon 220 provided at the tip of the catheter body 210, and a hub 230 fixed to the proximal end of the catheter body 210.

[0027] The balloon catheter 200 to which the implanted biological device 100 is attached constitutes the stent delivery system 300. The stent delivery system 300 delivers the implanted biological device 100, to which the porous structure 20 is attached, in a deflated state to the lesion site, and by expanding the stent 10 and the porous structure 20 as the balloon 220 expands, the stent 10 and the porous structure 20 can be placed in the lesion site.

[0028] The balloon catheter 200 can be constructed, for example, as a rapid exchange type balloon catheter that allows the guidewire W to be introduced from near the tip of the catheter body 210 and inserted through to the tip of the balloon 220. The balloon 220 can also be constructed as a so-called over-the-wire type balloon catheter.

[0029] For example, organic polymer materials can be used as the material constituting the balloon 220. Specifically, polymer materials such as polyolefins (e.g., polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or mixtures of two or more of these), polyvinyl chloride, polyamide, polyamide elastomer, polyurethane, polyurethane elastomer, polyimide, fluororesin, or mixtures thereof, or elastic resin materials such as two or more of the above polymer materials can be used, and among these, polyamide resins can be preferably used as the main material.

[0030] <100 living organisms> The implantable device 100 according to this embodiment is used to treat narrowing or obstruction in blood vessels, bile ducts, trachea, esophagus, urethra, or other biological tubular lumen. The porous structure 20 used in the implantable device 100 is positioned on a folded balloon 220 in a crimped state. The stent 10 is positioned to cover the outer circumference of the porous structure 20, which is crimped onto the balloon 220. The implantable device 100 is configured as a so-called balloon-expandable medical device that is delivered to the lesion and then expanded as the balloon 220 expands, allowing it to be implanted in the lesion.

[0031] The stent 10 can be made of, for example, a non-biodegradable material. Examples of non-biodegradable materials that can be used for the stent 10 include carbon fiber, metallic materials, and polymer materials. Preferably, the non-biodegradable material is a metallic material or a polymer material. From the viewpoint of further reducing inflammation associated with the placement of the stent 10, it is particularly preferable that the non-biodegradable material is a metallic material. Here, the metallic material used when the stent 10 is made of a metallic material is not particularly limited, and metallic materials commonly used in the field of stents can be used. Specifically, 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, which has the best corrosion resistance, is preferred. Among cobalt-based alloys, MP35N and L605 are preferred.

[0032] Furthermore, the stent 10 can be made of, for example, a polymer material. Examples of polymer materials that can be used for the stent 10 include those commonly used in the stent product field. Specifically, these include polyolefins such as polyethylene and polypropylene, aromatic polyesters such as polyethylene terephthalate, cellulosic polymers such as cellulose acetate and cellulose nitrate, and fluorine-containing polymers such as polytetrafluoroethylene and tetrafluoroethylene-ethylene copolymers.

[0033] Furthermore, the stent 10 can also be constructed as a so-called self-expanding medical device, made of a self-expanding material. When the stent 10 is self-expanding, it is preferable to use a superelastic alloy such as a nickel-titanium alloy, as a restoring force to its original shape is required.

[0034] As shown in Figures 2 to 4, the biological implantation 100 comprises an expandable stent 10 and a porous structure 20 positioned on the inner circumference side of the stent 10 (the side of the lumen 18 of the stent 10) and configured to expand in accordance with the expansion of the stent 10.

[0035] <Stent 10> As shown in Figures 2 to 4, the stent 10 has a cylindrical shape with an internal lumen 18 formed as it extends in the axial direction.

[0036] As shown in Figure 3, the stent 10 has linear rings 11 that form the outer circumference of a cylindrical shape with gaps, and link portions 12 that connect the rings 11 in gaps partitioned between adjacent linear rings 11 in the axial direction.

[0037] The ring 11 extends circumferentially around the stent 10 in a wave-like pattern that reciprocates in the axial direction.

[0038] The ring 11 has multiple first strut portions 14, which are made up of straight or curved lines, second strut portions 15, which are made up of straight or curved lines, and curved portions 17 formed between the first strut portions 14 and the second strut portions 15.

[0039] Furthermore, as shown in Figure 3, the ring 11 has a plurality of third strut portions 16, which are straight or curved, and are adjacent to one side of the link portion 12 in the axial direction and are provided in pairs in the circumferential direction.

[0040] The rings 11 are arranged sequentially along the axial direction. Adjacent rings 11 in the axial direction are connected and integrated by link portions 12.

[0041] The stent 10 can be, for example, a drug-eluting stent in which at least a portion of the stent 10 is coated with a drug. The drug coated on the stent 10 can be, for example, supported by a predetermined polymer to form the drug-carrying portion 60.

[0042] As shown in Figures 5 to 8, the drug-carrying portion 60 can be positioned, for example, on the outer surface 19b of the first strut portion 14 and / or the outer surface 19b of the third strut portion 16 of the ring 11. On the other hand, it is preferable not to form the drug-carrying portion 60 on the curved portion 17 and the link portion 12 of the ring 11 (the parts where stress concentration and / or strain occur as the stent 10 expands). By configuring it in this way, when the stent 10 expands, stress will concentrate on the drug-carrying portion 60, and as a result, bending and strain will occur in the drug-carrying portion 60, which can prevent the drug-carrying portion 60 from peeling off or falling off the stent 10.

[0043] Figure 7 shows a schematic cross-sectional view of the link section 12 (or curved section 17), and Figure 8 shows a schematic cross-sectional view of the first strut section 14 (or third strut section 16).

[0044] As shown in Figure 8, the drug-carrying portion 60 can be positioned on the outer surface 19b of the stent 10. This allows the drug-carrying portion 60 positioned on the outer surface 19b of the stent 10 to come into direct contact with the biological tissue on the inner wall surface of the biological lumen when the stent 10 is expanded, thereby improving the effect of the drug on the lesion.

[0045] <Porous structure 20> As shown in Figures 3, 5, and 6, the porous structure 20 has a mesh-like arrangement of skeletal parts 30 and a plurality of voids 40 partitioned by the skeletal parts 30.

[0046] As shown in Figure 3, the porous structure 20 is positioned in the lumen 18 of the stent 10 and has a cylindrical shape similar to the stent 10.

[0047] Preferably, the size of each of the multiple voids 40 in the porous structure 20 is smaller in area than the gap between the rings 11 of the stent 10. By adopting such a configuration, the porous structure 20 can prevent plaque and thrombi from entering the inside of the stent 10 and scattering as the stent 10 expands. On the other hand, preferably, the size of the voids 40 is larger than the area of ​​a single blood cell contained in the blood. This allows blood cells to pass through the voids 40. Furthermore, this allows the voids 40 to impart expandability to the porous structure 20. Therefore, when the stent 10 expands, the porous structure 20 also expands in the circumferential direction along with the expansion of the stent 10, exhibiting good followability (expandability) to the expansion of the stent 10.

[0048] There are no particular restrictions on the patterns (shapes in the unfolded view) of the skeletal portion 30 and void portion 40 of the porous structure 20.

[0049] The porous structure 20 can be made of, for example, knitted fabric, woven fabric (braid), or molded material (a membrane-like member with cuts formed on it). If the porous structure 20 is knitted fabric, it can be made by knitting. By making the porous structure 20 by knitting, it is possible to suppress the shortening of the axial length of the porous structure 20 as the stent 10 expands. If the porous structure 20 is woven fabric, the fabric can be made using known weaving methods. Alternatively, the porous structure 20 may be made of a molded material in which holes are made in a tubular object formed by injection molding or the like. The size, shape, and number of stitches and weaves of the porous structure 20 are not particularly limited as long as they can prevent peripheral embolism when the stent 10 expands.

[0050] In this embodiment, the implantable device 100 has a porous structure 20 positioned on the inner circumference (lumen 18 side) of the stent 10, which has the function of preventing the scattering of plaque and thrombi as the stent 10 expands, as described above. Therefore, when delivering the implantable device 100 to the lesion in the biological lumen, the porous structure 20 can be prevented from getting caught on the inner wall of the biological lumen, etc. Even if the area of ​​the void portion 40 of the porous structure 20 is formed to be extremely small compared to the gap between the rings 11 of the stent 10, the porous structure 20 can still be prevented from getting caught on the inner wall of the biological lumen, etc., as described above, so the scattering of plaque and thrombi can be effectively prevented by the porous structure 20.

[0051] As shown in Figures 5, 6, and 7, the biological implant 100 may have a fixing portion 70 for fixing the stent 10 and the porous structure 20.

[0052] The fixing portion 70 can be placed in a location on the stent 10 where the drug-carrying portion 60 is not provided. By fixing the porous structure 20 to the location on the stent 10 where the drug-carrying portion 60 is not provided via the fixing portion 70, the porous structure 20 and the stent 10 can be properly fixed to each other using the polymer material contained in the fixing portion 70 (the third biodegradable polymer material described later).

[0053] Examples of locations where the drug-carrying portion 60 is not located include the curved portion 17 and / or the link portion 12. As mentioned above, stress concentration and strain are likely to occur in the curved portion 17 and / or the link portion 12 when the stent 10 is expanded, so it is not preferable to place the drug-carrying portion 60 there (see Figures 5 and 6). In particular, the link portion 12 is a location where the axial geometry changes with the expansion of the stent 10 are minimal. Therefore, if the fixing portion 70 is provided on the link portion 12, tension on the porous structure 20 with the expansion of the stent 10 is not generated, and peeling or damage to the porous structure 20 can be suitably suppressed. For this reason, it is preferable to place the fixing portion 70 on at least a part of the link portion 12.

[0054] As shown in Figure 7, the fixing portion 70 can be positioned on the inner surface 19a side of the stent 10. This allows the inner surface 19a of the stent 10 to be fixed to the porous structure 20 positioned on the inner circumference side of the stent 10.

[0055] The fixing portion 70 can be formed, for example, by the following method.

[0056] As an example of a method for forming the fixing portion 70 with a polymer material (for example, a third biodegradable polymer material), a nozzle device capable of spraying polymer material (an ultrasonic spray nozzle device) can be used. In the method using the nozzle device, with the porous structure 20 placed in the lumen 18 of the stent 10, the nozzle is inserted into the lumen of the porous structure 20, and the polymer material is discharged from the inner circumference of the porous structure 20 toward the inner surface 19a of the stent 10. The fixing portion 70 can be formed by drying and solidifying the applied polymer material.

[0057] Another example of a method for forming the fixing portion 70 from a polymer material (for example, a third biodegradable polymer material) is to use a heating rod. In the method using a heating rod, the porous structure 20 is placed in the lumen 18 of the stent 10, and the polymer material is placed between the inner surface 19a of the stent 10 and the porous structure 20. A heating rod heated to a predetermined temperature is then inserted into the lumen of the porous structure 20. By moving the heated heating rod along the inner circumferential surface of the porous structure 20, the polymer material placed between the inner surface 19a of the stent 10 and the porous structure 20 is melted, and the stent 10 and the porous structure 20 are welded together. The fixing portion 70 can be formed by drying and solidifying the molten polymer material.

[0058] Furthermore, the stent 10 and the porous structure 20 can be fixed in a manner other than the fixation part made of polymer material. For example, a laser welding method can be used. When using the laser welding method, the porous structure 20 is placed in the lumen 18 of the stent 10, and a laser is irradiated from the outside of the stent 10. At this time, the welding point (focal position) of the laser is set to the inner surface 19a of the stent 10 that is facing the porous structure 20. This allows the stent 10 and the porous structure 20 to be laser-welded together.

[0059] In this embodiment, the porous structure 20 can be made of a first biodegradable polymer material. Furthermore, the drug-carrying portion 60 of the stent 10 may contain a second biodegradable polymer material and a drug.

[0060] Regarding the relationship between the decomposition time of the porous structure 20 and the decomposition time of the drug-carrying portion 60, it is preferable that the decomposition time of the porous structure 20 is substantially the same as, or shorter than, the decomposition time of the drug-carrying portion 60 (decomposition time of porous structure 20 ≤ decomposition time of drug-carrying portion 60). A biological implant 100 placed in a biological lumen may cause inflammation at the contact point with the biological tissue on the inner wall of the biological lumen. In contrast, with the decomposition time relationship described above, the drug continues to be released from the drug-carrying portion 60 to the biological tissue for most of the period that the porous structure 20 is present. Therefore, this configuration can more effectively prevent and suppress the inflammatory response of the biological tissue associated with the decomposition of the porous structure 20 (first biodegradable polymer material). Thus, it is possible to achieve both the suppression and prevention of peripheral embolism and the reduction and elimination of the risk of inflammation of the biological tissue at the stent placement site.

[0061] For example, the decomposition time of the porous structure 20 can be shorter than the decomposition time of the drug-carrying portion 60. With this configuration, the drug-carrying portion 60 decomposes and disappears after the porous structure 20 has decomposed and disappeared. Throughout the entire period that the porous structure 20 is present, the drug continues to be released from the drug-carrying portion 60 into the living tissue. Therefore, with this configuration, the inflammatory response associated with the decomposition of the porous structure 20 (the first biodegradable polymer material) can be effectively prevented and suppressed. Here, the difference between the decomposition time of the porous structure 20 and the decomposition time of the drug-carrying portion 60 (= decomposition time of the drug-carrying portion 60 - decomposition time of the porous structure 20) is preferably 0.2 months to 15 months, preferably 0.5 months to 12 months, and preferably 1.0 month to 3.0 months. If such a time difference is provided, it is possible to achieve a better balance between suppressing and preventing peripheral embolism and reducing and eliminating the risk of inflammation in living tissue.

[0062] Furthermore, for example, the decomposition time of the porous structure 20 can be substantially the same as the decomposition time of the drug-carrying portion 60. With this configuration, the drug-carrying portion 60 decomposes and disappears around the same time as 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 portion 60 into the living tissue. For this reason, this configuration can effectively prevent and suppress the inflammatory response associated with the decomposition of the porous structure 20 (the first biodegradable polymer material). Here, "the decomposition time of the porous structure 20 is substantially the same as the decomposition time of the drug-carrying portion 60" means that the difference between the decomposition time of the porous structure 20 and the decomposition time of the drug-carrying portion 60 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 portion 60 (the above difference is 0 hours).

[0063] In the biological implant 100, the drug contained in the drug-carrying portion 60 is not particularly limited and can be appropriately selected according to the desired use. Considering the induction of inflammation by the porous structure 20 and the fixation portion 70, the drug preferably contains an anti-inflammatory agent or an immunosuppressant. Here, the anti-inflammatory agent is not particularly limited and known anti-inflammatory agents can be used. The anti-inflammatory agent is a steroidal anti-inflammatory agent, a non-steroidal anti-inflammatory agent, or a combination thereof. For example, anti-inflammatory agents include alclofenac, alclomethasone dipropionate, algestone acetonide, alpha-amylase, amsinafar, amsinafid, amfenac sodium, ampyrrose hydrochloride, anakinra, anirolac, anitrazafen, apazon, valsalazid disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelain, broperamol, budesonide, carprofen, and cycloprofen. Syntazone, criprofen, clobetasol propionate, clobetazone butyrate, clopirac, cloticasone propionate, colmethasone acetate, cortodoxone, deflazacort, desonide, desoxymethasone, dexamethasone, dexamethasone dipropionate, diclofenac potassium, diclofenac sodium, diflorazone diacetate, diflumidone sodium, diflunisal, difluprednate, diphthalone, dimethyl sulfoxide, do Rocinonide, Endrizone, Enlimomab, Enolicum sodium, Epirizol, Etodrug, Etofenamate, Felbinac, Fenamol, Fenbufen, Fenclofenac, Fenclolac, Fendozal, Fenpiparone, Fenthiazac, Flazaron, Fluazacort, Flufenamic acid, Flumizole, Flunisolid acetate, Flunixin, Flunixin meglumine, Fluocortin butyl, Fluorometholone acetate, Flu Quazone, flurbiprofen, fluretofen, fluticasone propionate, flaprofen, flobufen, halcinonide, halobetazole propionate, halopredone acetate, ibufenac, ibuprofen, ibuprofen aluminum, ibuprofen piconol, ironidap, indomethacin, indomethacin sodium, indoprofen, indoxol, intrazol, isoflupredone acetate, isoxepak, isoxicam,Ketoprofen, lofemisole hydrochloride, romoxicam, loteprednol etavonate, sodium meclofename, meclofenamic acid, mechlorizone dibutyrate, mefenamic acid, mesalamine, mesecrazone, prednisolone, methylprednisolone sleptanoate, momiflumate, nabumetone, naproxen, naproxen sodium, naproxol, nimazon, olsalazine sodium, olgotein, orpanoxin, oxaprozin, oxyfenbutazone, paraniline hydrochloride, sodium pentosan polysulfate, fenbutazone sodium glycerate, pirfenidone, piroxicam, piroxicam cinnamate, piroxicam olamine, pirprofen, prednazate, priferon, prodolic acid, proquazone, prox Examples include sazole, proxazole citrate, rimexolone, romazalit, sarcorex, sarnasedin, sarsalate, sanguinalium chloride, secrazone, selmethacin, sudoxicam, sulindac, suprofen, talmetacin, talniflumate, talosalate, tebuferon, tenidap, tenidap sodium, tenoxicam, tesicam, tesimide, tetridamine, thiopinac, thixocortol pivalate, tolmetin, tolmetin sodium, triclonide, triflumidate, zidomethacin, zomepirac sodium, aspirin (acetylsalicylic acid), salicylic acid, corticosteroids, glucocorticoids, tacrolimus, pimecorlimus, their prodrugs, and their codrugs. The above anti-inflammatory agents may be used individually or in combination of two or more.

[0064] Immunosuppressants are 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®), tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, and gusperimus. The above immunosuppressants may be used individually or in combination of two or more. Furthermore, the above immunosuppressants may be used in combination with anti-inflammatory agents.

[0065] Here, the amount of drug in the drug-carrying portion 60 is not particularly limited as long as it is an amount that produces the desired therapeutic effect, but from the viewpoint of further exhibiting anti-inflammatory effects, it is preferable to include a larger amount of drug. Specifically, the amount of drug in the drug-carrying portion 60 is preferably 30% to 60% by mass, more preferably 45% to 50% by mass, and particularly preferably 50% by mass, based on the total amount (100% by mass) of the second biodegradable polymer material and the drug. With this composition, an appropriate amount of drug can be effectively released over a predetermined period.

[0066] In this embodiment, the fixing portion 70 that secures the stent 10 and the porous structure 20 may include a third biodegradable polymer material.

[0067] Preferably, the decomposition time of the fixation part 70 is substantially the same as, or shorter than, the decomposition time of the drug-carrying part 60 (decomposition time of fixation part 70 ≤ decomposition time of drug-carrying part 60). If the fixation part 70 is made of a non-biodegradable material, the fixation part 70 may remain in the body as a foreign body, potentially causing undesirable events such as restenosis. On the other hand, even if a biodegradable material is used for the fixation part 70, many biodegradable materials can cause inflammation during the decomposition process. In contrast, according to this embodiment, the drug-carrying part 60 decomposes and disappears at the same time as, or after, the fixation part 70 has decomposed and disappeared. Therefore, the drug continues to be released from the drug-carrying part 60 into the living tissue until the fixation part 70 decomposes and disappears. Therefore, according to the biological implantation device 100 of this embodiment, the inflammatory response associated with the decomposition of the fixation part 70 during stent placement can be effectively prevented and suppressed. For example, if the decomposition time of the fixing part 70 is longer than the decomposition time of the drug-carrying part 60 (decomposition time of fixing part 70 > decomposition time of drug-carrying part 60), the fixing part 70 will remain beyond the drug dissolution period, and the possibility of causing restenosis or other problems cannot be ruled out.

[0068] Furthermore, the decomposition time of the fixation part 70 can be shorter than the decomposition time of the drug-carrying part 60. With this configuration, the drug-carrying part 60 decomposes and disappears after the fixation part 70 has decomposed and disappeared. Throughout the entire period that the fixation part 70 is present, the drug continues to be released from the drug-carrying part 60 to the living tissue. Therefore, with this configuration, the inflammatory response associated with the decomposition of the fixation part 70 can be effectively prevented and suppressed. Here, the difference between the decomposition time of the fixation part 70 and the decomposition time of the drug-carrying part 60 (= decomposition time of drug-carrying part 60 - decomposition time of fixation part 70) is preferably 0.1 months or more and 15 months or less, more preferably 0.5 months or more and 12 months or less. In this specification, one month is treated as 30 days.

[0069] Furthermore, the decomposition time of the fixing part 70 can be substantially the same as the decomposition time of the drug-carrying part 60. With this configuration, the drug-carrying part 60 decomposes and disappears around the same time as the fixing part 70. Therefore, for most of the time the fixing part 70 is present, the drug continues to be released from the drug-carrying part 60 to the living tissue. For this reason, this configuration can effectively prevent and suppress the inflammatory response associated with the decomposition of the fixing part 70. Here, "the decomposition time of the fixing part 70 is substantially the same as the decomposition time of the drug-carrying part 60" means that the difference between the decomposition time of the fixing part 70 and the decomposition time of the drug-carrying part 60 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 70 is the same as the decomposition time of the drug-carrying part 60 (the above difference is 0 hours).

[0070] Furthermore, it is preferable that the decomposition time of the porous structure 20 is shorter than the decomposition time of the fixing part 70. With this configuration, the fixing part 70 decomposes and disappears after the porous structure 20 has decomposed and disappeared. Therefore, for the entire period that the porous structure 20 is present, the porous structure 20 is fixed to the stent 10 via the fixing part 70. Thus, even when the implanted biological device 100 is placed in the coronary artery of a patient with acute myocardial infarction, displacement or detachment of the porous structure 20 from the implanted biological device 100 (stent 10) due to vascular pulsation can be effectively suppressed. Here, the difference between the decomposition time of the porous structure 20 and the decomposition time of the fixing part 70 (= decomposition time of the fixing part 70 - decomposition time of the porous structure 20) is, for example, 0.1 months or more and 4 months or less, preferably 0.2 months or more and 3 months or less, and more preferably 1.0 month or more and 2.5 months or less.

[0071] The decomposition time of the porous structure 20, the drug-carrying portion 60, and the fixing portion 70 can be controlled by the type of first biodegradable polymer material constituting the porous structure 20, the type of second biodegradable polymer material constituting the drug-carrying portion 60, and the type of third biodegradable polymer material constituting the fixing portion 70. It is considered that the size of the first biodegradable polymer material, the second biodegradable polymer material, and the third biodegradable polymer (in materials where the entire material decomposes uniformly) has little to no effect on the decomposition time (decomposition rate, solubility).

[0072] The biodegradable polymer materials that can be used as the first biodegradable polymer material, the second biodegradable polymer material, and the third biodegradable polymer material are not particularly limited and can be appropriately selected from known biodegradable polymer materials according to the relative decomposition times of each material.

[0073] As the biodegradable polymer materials described above, known biodegradable polymer materials such as those described in Japanese Patent Publication No. 2011-528275, Japanese Patent Publication No. 2008-514719, International Publication No. 2008 / 1952, and Japanese Patent Publication No. 2004-509205 can be used. Specifically, examples include (1) polymers selected from the group consisting of aliphatic polyesters, polyesters, polyacid anhydrides, polyoltoesters, polycarbonates, polyphosphazenes, polyphosphate esters, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose; and (2) copolymers composed of two or more monomers constituting (1) above. Here, the aliphatic polyester is not particularly limited and includes, for example, polylactic acid (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. Furthermore, the polycarbonate is not particularly limited and includes, for example, tyrosine-polycarbonate.

[0074] Next, a biological implant relating to a modified embodiment described above will be explained. In the explanation of the modified embodiment, explanations that overlap with those described in the previously described embodiment will be omitted as appropriate. Unless otherwise specified, the biological implant relating to the modified embodiment can incorporate the same components as those described in the previously described embodiment.

[0075] <Example 1> Figure 9 is a plan view showing the reduced diameter state of the biological implant 100 according to the modified example 1. Figure 10 is an enlarged view showing a part of the cross-sectional area perpendicular to the axis of the base end 20B of the porous structure 20, and Figure 11 is a cross-sectional view along the axial direction of the base end 20B of the porous structure 20.

[0076] As shown in Figures 9 to 11, the porous structure 20 according to Modification 1 has a mesh-like arrangement of skeletal parts 30, a plurality of voids 40 partitioned by the skeletal parts 30, and a covering part 50 containing a polymer material that is arranged to cover at least a part of the porous structure 20.

[0077] As shown in Figures 10 and 11, the covering portion 50 has uneven surfaces 53 formed along the surface shape of the porous structure 20.

[0078] The biological implant 100 is protected by a covering portion 50 which covers at least a portion of the porous structure 20, thereby preventing the porous structure 20 (especially the void portion 40) from getting caught on the biological lumen (e.g., blood vessel) when the biological implant 100 moves within the biological lumen. Furthermore, because the covering portion 50 of the biological implant 100 contains a polymer material, it is possible to prevent an excessive reduction in the flexibility of the area of ​​the porous structure 20 where the covering portion 50 is provided. Therefore, it is possible to prevent a decrease in the deliverability of the biological implant 100 or a decrease in the expandability of the porous structure 20 as a result of providing the covering portion 50.

[0079] Furthermore, the biological implant 100 has a coating portion 50 with uneven surfaces 53 formed along the surface shape of the porous structure 20. In other words, the coating portion 50 is not formed with a uniform thickness across all parts of the porous structure 20, and some parts of the coating portion 50 are thinner than other parts of the coating portion 50 (for example, the protrusions 53a). Therefore, the amount of coating portion 50 required (the volume of polymer material contained in the coating portion 50) is reduced compared to the case where the coating portion 50 is provided with a uniform thickness across the entire porous structure 20.

[0080] As shown in Figures 10 and 11, the covering portion 50 has a convex portion 53a that has a convex shape at a position corresponding to the skeletal portion 30, and a recessed portion 53b that has a smaller covering amount than the convex portion 53a at a position corresponding to the void portion 40.

[0081] In the covering portion 50, the skeletal portion 30 and the void portion 40 are arranged alternately in the circumferential direction of the porous structure 20. Therefore, as shown in Figure 10, the covering portion 50 has convex portions 53a provided in the areas where the skeletal portion 30 is located and concave portions 53b provided in the areas where the void portion 40 is located, which are arranged alternately along the circumferential direction of the porous structure 20.

[0082] The porous structure 20 has a recess 53b with a small thickness formed in a part of the covering portion 50, thus reducing the amount of covering portion 50 that needs to be installed. Furthermore, because the porous structure 20 has a recess 53b formed in the covering portion 50, when the porous structure 20 expands in conjunction with the expansion of the stent 10, the expansion of the porous structure 20 at the location where the recess 53b is formed can be prevented. Therefore, by providing the recess 53b, the porous structure 20 can prevent the smooth expansion of the porous structure 20 from being hindered by the presence of the covering portion 50.

[0083] In particular, in this embodiment, as shown in Figure 10, the covering portion 50 has convex portions 53a and concave portions 53b arranged alternately in the circumferential direction. Therefore, when the porous structure 20 expands, each of the concave portions 53b located between adjacent convex portions 53a in the circumferential direction begins to expand quickly. Thus, when the porous structure 20 expands, it becomes possible to uniformly expand each part of the porous structure 20 in the circumferential direction.

[0084] As shown in Figure 9, the covering portion 50 can be positioned at least one of the two ends 20A and 20B located in the axial direction (longitudinal direction) of the porous structure 20.

[0085] In this modified example, the covering portion 50 is placed at both ends 20A and 20B of the porous structure 20. However, for example, the covering portion 50 may be placed only at the tip end 20A of the porous structure 20, or only at the base end 20B of the porous structure 20. The following description will focus on the covering portion 50 placed at the base end 20B of the porous structure 20, but the covering portion 50 provided at the tip end 20A can be configured in the same way as the covering portion 50 placed at the base end 20B.

[0086] As shown in Figure 11, the amount of coverage of the covering portion 50 gradually decreases from the base end portion 20B located in the axial direction of the porous structure 20 to the central portion 20C (near the axial center of the porous structure 20). In other words, the thickness of the covering portion 50 provided at the base end portion 20B of the porous structure 20 gradually decreases toward the tip end portion 20A located on the opposite side in the axial direction. Similarly, the thickness of the covering portion 50 provided at the tip end portion 20A of the porous structure 20 gradually decreases toward the base end portion 20B located on the opposite side in the axial direction.

[0087] For example, as a manufacturing method for the porous structure 20, a porous structure longer than the length intended for use in the product may be prepared and cut at a predetermined position. When such a manufacturing method is adopted, both ends 20A and 20B of the porous structure 20 will be made up of the cut ends. Since the porous structure 20 has a mesh structure consisting of a skeletal part 30 and a void part 40, fraying and irregularities are likely to occur at the cut ends, which may result in a shape that spreads radially outward. When both ends 20A and 20B of the porous structure 20 are formed in this way, the porous structure 20 is more likely to get caught in biological tubules or the like.

[0088] In this embodiment, by arranging the covering portion 50 at both ends 20A and 20B of the porous structure 20, it is possible to prevent the fraying and variations described above from occurring at both ends 20A and 20B. Furthermore, since the amount of covering portion 50 is gradually reduced from each end 20A and 20B located in the axial direction of the porous structure 20 toward the axial center, the amount of covering portion 50 can be reduced even more effectively. In addition, when moving the biological implant 100 within a biological lumen, both ends 20A and 20B in the axial direction of the porous structure 20 are prone to contact with the inner wall of the biological lumen, and are particularly likely to get caught on the porous structure 20. By covering at least one end of both ends 20A and 20B in the axial direction of the porous structure 20 with the covering portion 50, as in this embodiment, it is possible to effectively prevent the porous structure 20 from getting caught on the inner wall of the biological lumen, etc.

[0089] Furthermore, the porous structure 20 can be fixed to the stent 10 via the covering portion 50. By fixing the porous structure 20 to the stent 10 via the covering portion 50, it is possible to prevent fraying or inconsistencies in the porous structure 20 at the cutting position when the porous structure 20 is cut at the position where the covering portion 50 is provided during the manufacturing of the porous structure 20.

[0090] Furthermore, the porous structure 20 can be fixed to the stent 10 via the covering portion 50 in areas where the drug-carrying portion 60 is not located. By fixing the porous structure 20 to the stent 10 only in areas where the drug-carrying portion 60 is not located, the polymer material contained in the covering portion 50 can be used to appropriately fix the covering portion 50, the porous structure 20, and the stent 10 to each other. Examples of areas where the drug-carrying portion 60 is not located include the curved portion 17 and / or the link portion 12.

[0091] The polymer material contained in the covering portion 50 is, for example, a biodegradable polymer. By constructing the covering portion 50 in this manner, the covering portion 50 can be decomposed and disappear after a predetermined period of time has elapsed since the stent 10 was placed in place. Furthermore, by using a biodegradable polymer as the polymer material, the impact on the human body caused by placing the covering portion 50 together with the stent 10 and the porous structure 20 can be reduced. The polymer material constituting the covering portion 50 can be, for example, the same as the third biodegradable polymer material used in the fixing portion 70 described above.

[0092] The polymer material contained in the covering portion 50 has physical properties such as a Young's modulus less than 10 MPa. By configuring the covering portion 50 in this way, it is possible to prevent the smooth expansion of the porous structure 20 from being hindered by the covering portion 50 when the stent 10 expands.

[0093] <Modification 2> The covering portion 50 of the porous structure 20 according to the modified example 1 described above includes an uneven portion 53 formed along the surface shape of the porous structure 20 (see Figures 10 and 11). On the other hand, as shown in Figures 12 and 13, the covering portion 50A according to this modified example 2 is arranged only along the skeletal portion 30 surrounding the void portion 40, and is not positioned at a location corresponding to the void portion 40.

[0094] As shown in Figures 12 and 13, the covering portion 50A is configured to form an outer layer that covers the skeletal portion 30.

[0095] In the porous structure 20 according to Modification 2, the covering portion 50A is not formed in a position where the void portion 40 exists. In other words, unlike Modification 1 described above, there is no recess 53b arranged to fill the void portion 40. Therefore, the amount of covering portion 50A to be installed is further reduced compared to the covering portion 50 according to Modification 1 described above. Also, since there is no recess 53b arranged to fill the void portion 40 as described above, the flexibility of the porous structure 20 in the position corresponding to the void portion 40 can be improved. Furthermore, the bulkiness caused by providing the covering portion 50A when the stent 10 is crimped into the porous structure 20 (the state in which the biological implant 100 is formed) can be reduced.

[0096] As shown in Figure 13, in the porous structure 20 according to Modification 2, the amount of covering portion 50A gradually decreases from the end located in the axial direction of the porous structure 20 (the base end 20B in the illustrated example) to the central part (towards the direction of arrow X1 in the figure). By configuring it in this way, as explained in Modification 1 above, it is possible to reduce the amount of covering portion 50A while preventing fraying and inconsistencies from occurring at the ends of the porous structure 20.

[0097] In the modified example 2, an example was described in which a covering portion 50A is formed on the proximal end portion 20B of the porous structure 20. However, it is also possible to adopt a configuration in which the covering portion 50A is provided on the tip portion 20A and / or the proximal end portion 20B of the porous structure 20. Furthermore, although not described here, the covering portion 50A can be configured to fix the porous structure 20 to the stent 10 at a predetermined position (for example, in an area where the drug-carrying portion 60 is not formed), similar to the embodiment described above.

[0098] In Modification 1 and Modification 2, the tip portion 20A and / or base portion 20B were given as examples of locations for forming the covering portion 50 (or covering portion 50A) on the porous structure 20. However, there are no particular restrictions on the location where the covering portion 50 is provided in the biological implant according to the present invention, and it can be provided at any location, at least a part of the porous structure 20.

[0099] Although the biological implantation device according to the present invention has been described above through embodiments and modifications, the present invention is not limited to the configuration described in the embodiments and can be modified as appropriate based on the claims. [Explanation of Symbols]

[0100] 10 stents 10A Stent Tip 10B Stent base 11 rings 12 Link section 14. First strut section 15. Second strut section 16. Third strut section 17 Curved section 18. Lumen of the stent 19a Inner surface of the stent 19b Outer surface of the stent 20 Porous structure 20A Tip of the porous structure 20B Base of a porous structure 30 Skeletal parts 40 Cavity 50 Covering part 50A Insulated part 53 Uneven part 53a Convex part 53b Recess 60 Drug handling section 70 Fixed part 100 Living organisms 200 balloon catheters 220 balloons 300 Stent Delivery System

Claims

1. A cylindrical stent that can be expanded in diameter, A biological implant comprising: a porous structure disposed on the inner circumference side of the stent and configured to expand as the diameter of the stent expands.

2. The porous structure is composed of a first biodegradable polymer, The stent has a drug-carrying portion containing a second biodegradable polymer and a drug, The biological implant 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 stent and the porous structure are fixed together, and the fixing portion further includes a third biodegradable polymer material. The biological implant according to claim 2, wherein the fixing portion is located in a place in the stent where the drug-carrying portion is not provided.

4. The stent has a plurality of wavy rings forming the outer circumference of a cylindrical shape, and link portions connecting adjacent rings. The aforementioned link portion is not provided with the drug-carrying portion. The biological implant according to claim 3, wherein the fixing portion is arranged on at least a part of the link portion.

5. The biological implant according to claim 3 or 4, wherein the decomposition time of the fixed portion is substantially the same as, or shorter than, the decomposition time of the drug-carrying portion.

6. The aforementioned porous structure is A skeletal structure arranged in a mesh-like pattern, Multiple voids partitioned by the aforementioned skeletal portion, The porous structure has a covering portion which includes a polymer material disposed to cover at least a part of the porous structure, The biological implant according to claim 1, wherein the covering portion has an uneven portion formed in accordance with the surface shape of the porous structure.

7. The aforementioned porous structure is A skeletal structure arranged in a mesh-like pattern, Multiple voids partitioned by the aforementioned skeletal portion, The porous structure comprises a coating portion including a polymer material disposed to cover at least a portion of the outer surface of the porous structure, The biological implant according to claim 1, wherein the covering portion is arranged only along the skeletal portion surrounding the void and is not arranged at a position corresponding to the void.

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