Biocompatible implant

Abstract

To provide a biocompatible implant capable of effectively suppressing onset of inflammation derived from a porous structure, while preventing scattering of plaque and clot during stent expansion.SOLUTION: A biocompatible implant 100 includes an expandable tubular stent 10, a porous structure 20 made of a first biodegradable polymer arranged to cover the stent, and a micro drug carrier 30 containing a second biodegradable polymer and a drug. The micro drug carrier is at least partially embedded within the porous structure and / or at least partially carried on the outer surface of the porous structure, and the degradation time of the porous structure is either substantially the same as or shorter than the degradation time of the micro drug carrier.SELECTED DRAWING: Figure 6

Description

[Technical field]

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

[0002] A stent is a medical device that is delivered to a lesion in a biological lumen by a stent delivery system and then placed to expand the lesion, such as a stenosis or occlusion, and secure the lumen in order to treat various diseases caused by the narrowing or occlusion of a biological lumen such as a blood vessel. 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 it is expanded (expanded) in the biological lumen. The stent maintains its tensile strength for a predetermined period of time, thereby maintaining the lesion in an expanded state and securing the lumen of the biological lumen.

[0003] For example, Patent Document 1 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, a mesh having 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. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2006 / 126182 Summary of the Invention [Problem to be solved by the invention]

[0005] In mesh-covered stents, a polymer mesh is sometimes used to improve the mesh's ability to follow the stent when it expands, improve its delivery to the lesion, and reduce the impact on the biological lumen after treatment. However, when a polymer mesh is used, the following points are of concern:

[0006] Generally, polymer materials are more likely to cause inflammation in tissues than metal materials. In view of this, in known drug-eluting stents, when a polymer is used as a drug carrier, a biodegradable polymer or a bioinert polymer is often selected. However, it is believed that inflammation caused by the polymer can be suppressed by the drug released (eluted) from the stent. Therefore, when a biodegradable polymer is used as a constituent material of a stent, it is believed that the effect of inflammation caused by the polymer can be reduced by using a polymer that disappears quickly after the drug release is completed.

[0007] Taking the above points into consideration, in a mesh-covered stent comprising a polymer mesh, by adjusting the time from when the mesh-covered stent is placed until the polymer mesh decomposes and disappears, and the time from when the mesh-covered stent is placed until the release of the drug is completed, it is believed that it is possible to effectively suppress the onset of inflammation caused by the polymer mesh while preventing the scattering of plaque and thrombus when the stent is expanded.

[0008] However, when a drug is directly incorporated into the polymer mesh itself, the time until the polymer mesh decomposes and disappears and the time until the drug release is completed are essentially the same, making it difficult to determine a relationship between the two.

[0009] The present invention has been made in consideration of the above-mentioned problems, and has an object to provide an in-vivo indwelling device that can effectively suppress the onset of inflammation derived from a porous structure made of a biodegradable polymer while preventing the scattering of plaque and thrombus during stent expansion. [Means for solving the problem]

[0010] The above object of the present invention can be achieved by any one of the following means (1) to (13).

[0011] (1) A biological indwelling device comprising an expandable tubular stent, a porous structure made of a first biodegradable polymer arranged to cover the stent, and a micro-drug carrier containing a second biodegradable polymer and a drug, wherein at least a portion of the micro-drug carrier is embedded within the porous structure and / or at least a portion of the micro-drug carrier is supported on the outer surface of the porous structure, and the decomposition time of the porous structure is substantially the same as or shorter than the decomposition time of the micro-drug carrier.

[0012] (2) The indwelling device according to (2) above, wherein the first biodegradable polymer and the second biodegradable polymer are the same polymer, and the first biodegradable polymer and the second biodegradable polymer are selected from the group consisting of homopolymers of one type of monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or copolymers of two or more types of monomers.

[0013] (3) the first biodegradable polymer and the second biodegradable polymer are different polymers, and the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polycaprolactone, glycolic acid-lactic acid copolymer, ε-caprolactone-lactic acid copolymer, and glycolic acid-ε-caprolactone copolymer; 2. The indwelling device according to claim 1, wherein the second biodegradable polymer is at least one selected from the group consisting of polylactic acid, lactic acid-ε-caprolactone copolymer, and lactic acid-glycolic acid copolymer.

[0014] (4) The indwelling device according to the above-mentioned (3), wherein the molecular weight of the first biodegradable polymer and the second biodegradable polymer is 20,000 or more and 500,000 or less.

[0015] (5) The living body indwelling device according to any one of the above (1) to (4), wherein the decomposition time of the porous structure is within 4 months.

[0016] (6) The living body indwelling device according to any one of the above (1) to (5), wherein the decomposition time of the micro drug carriers exceeds 4 months.

[0017] (7) The living body indwelling device according to any one of the above (1) to (6), wherein the porous structure and the micro drug carriers have a number average molecular weight of less than 2,000 in a decomposed state.

[0018] (8) The living body indwelling device according to any one of the above (1) to (7), wherein the micro drug-carrying bodies are granular, needle-like, or pyramidal.

[0019] (9) The living body indwelling device according to any one of the above (1) to (8), wherein the micro drug carrier further contains a sterol, and a fatty acid or a phospholipid.

[0020] (10) The indwelling device according to any one of the above (1) to (9), wherein the stent is made of a metal material or a polymer material.

[0021] (11) The living body indwelling device according to any one of the above (1) to (10), wherein the medicine includes an anti-inflammatory agent.

[0022] (12) The indwelling device according to any one of (1) to (11) above, wherein the proportion of the drug in the micro drug carrier is 40% by mass or more and 55% by mass or less relative to the total amount of the second biodegradable polymer and the drug.

[0023] (13) The porous structure includes a coating layer containing the micro drug carrier, The living body indwelling device according to any one of the above (1) to (12), wherein the coating layer contains an adhesion promoter that adheres the micro drug-carrying bodies to living tissue. Effect of the Invention

[0024] According to the above-mentioned indwelling device, the porous structure decomposes and disappears after a certain period of time has elapsed since placement, and the release of the drug from the micro drug carriers continues until the porous structure decomposes and disappears. Therefore, the above-mentioned indwelling device can effectively suppress the onset of inflammation caused by the porous structure made of a biodegradable polymer while preventing the scattering of plaque or thrombus during stent expansion. [Brief description of the drawings]

[0025] [Figure 1] FIG. 1 is a schematic plan view showing a stent delivery system including a living body indwelling device according to an embodiment. [Diagram 2] FIG. 2 is a schematic plan view showing a reduced diameter state of the living body indwelling device according to the embodiment. [Diagram 3] FIG. 2 is a schematic plan view showing an expanded state (diameter-expanded state) of the living body indwelling device according to the embodiment. [Figure 4] FIG. 4 is a partially enlarged view showing a part of the living body indwelling in the state shown in FIG. 3. [Diagram 5] FIG. 2 is an enlarged cross-sectional view showing a cross section of a portion of a stent and a porous structure. [Figure 6] FIG. 2 is a cross-sectional view showing a simplified example of the arrangement of micro drug carriers in a porous structure. [Figure 7] FIG. 2 is a cross-sectional view showing a simplified example of the arrangement of micro drug carriers in a porous structure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] Hereinafter, an embodiment of the present invention will be described with reference to the attached drawings. Note that the following description does not limit the technical scope or meaning of terms described in the claims. Also, the dimensional ratios in the drawings are exaggerated for the convenience of explanation and may differ from the actual ratios.

[0027] Hereinafter, the living body indwelling device 100 according to this embodiment will be described with reference to Figs.

[0028] Fig. 1 is a schematic plan view showing a stent delivery system 300 including a living body indwelling device 100 according to an embodiment of the present invention. Fig. 2 is a schematic plan view showing a contracted state of the living body indwelling device 100 according to an embodiment. Fig. 3 is a schematic plan view showing a expanded state of the living body indwelling device 100 according to an embodiment. Fig. 4 is a partially enlarged view showing the living body indwelling device 100 according to an embodiment. Fig. 5 is a partially enlarged cross-sectional view of a stent 10 and a porous structure 20. Figs. 6 and 7 are cross-sectional views showing schematic examples of arrangement of micro drug carriers 30 in the porous structure 20.

[0029] In this specification, the direction in which the living body indwelling device 100 extends is referred to as the "axial direction." The above-mentioned axial direction is the direction from the distal end 10A to the proximal end 10B shown in FIG. 2. The side inserted into the living body is referred to as the "distal side," and the side opposite the distal end where the surgeon operates the stent delivery system 300 is referred to as the "proximal side." The direction perpendicular to the above-mentioned "axial direction" is referred to as the "radial direction" of the living body indwelling device 100.

[0030] As shown in FIG. 1, the stent delivery system 300 includes an indwelling device 100 and a balloon catheter 200.

[0031] <Balloon Catheter 200> The balloon catheter 200 is delivered in a deflated state to the affected area, and is used to expand and place the indwelling device 100 near the affected area.

[0032] 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 .

[0033] The catheter body 210 comprises an outer tube and an inner tube disposed inside the outer tube.

[0034] An expansion lumen is formed inside the outer tube, through which an expansion fluid flows for expanding the balloon 220. The distal end of the outer tube is fixed to the proximal end of the balloon 220. The proximal end of the outer tube is fixed to the hub 230.

[0035] A guidewire lumen into which a guidewire is inserted is formed inside the inner tube. The distal end of the inner tube passes through the inside of the balloon 220 and opens distally beyond the balloon 220. The proximal end of the inner tube passes through the sidewall of the outer tube proximal to the balloon 220 and is fixed to the outer tube.

[0036] The catheter body 210 is preferably made of a material having a certain degree of flexibility, and examples thereof include polyolefins such as polyethylene, polypropylene, polybutene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, ionomer, or a mixture of two or more of these; thermoplastic resins such as polyvinyl chloride resin, polyamide, polyamide elastomer, polyester, polyester elastomer, polyurethane, and fluororesin; silicone rubber; and latex rubber.

[0037] The balloon 220 is a member that, for example, expands inside a stenosis (lesion) to push open the stenosis. The tip side of the balloon 220 is fixed to the outer wall surface of the inner tube. The base end side of the balloon 220 is fixed to the outer wall surface of the tip of the outer tube. Therefore, the inside of the balloon 220 communicates with an expansion lumen formed in the outer tube. The balloon 220 is capable of receiving an expansion fluid from a base end opening 231 via the expansion lumen. The balloon 220 expands due to the inflow of the expansion fluid, and contracts and becomes folded by discharging the inflowing expansion fluid.

[0038] The material of the balloon 220 is preferably a flexible material that expands and contracts with the inflow and outflow of the expansion fluid, and examples thereof include polymeric materials such as polyolefin, crosslinked polyolefin, polyester, polyester elastomer, polyvinyl chloride, polyurethane, polyurethane elastomer, polyphenylene sulfide, polyamide, polyamide elastomer, fluororesin, silicone rubber, and latex rubber. The material of the balloon 220 is not limited to the above polymeric materials used alone, and a film in which the above polymeric materials are appropriately laminated may be used. The expansion fluid may be a gas or a liquid, and examples thereof include gases such as helium gas, CO2 gas, and O2 gas, and liquids such as saline and X-ray contrast medium.

[0039] The hub 230 has a proximal opening 231 that communicates with the inflation lumen of the outer tube. The proximal opening 231 functions as a port for the inflow and outflow of the inflation fluid.

[0040] The material of which the hub 230 is made is not particularly limited, but examples include thermoplastic resins such as polyethylene, polyurethane, polyester, polypropylene, polycarbonate, polyamide, polysulfone, polyarylate, and methacrylate-butylene-styrene copolymer.

[0041] <100 living body specimens> In this embodiment, the indwelling device 100 is used to treat, for example, a narrowed or blocked area that occurs in a blood vessel, a bile duct, a trachea, an esophagus, a urethra, or other body lumen. The indwelling device 100 is a so-called balloon expansion type device that is mounted on a balloon 220 in a crimped state, and is expanded after being delivered to the affected area and placed in the affected area.

[0042] As shown in Figures 2 to 7, the in-vivo implant 100 generally comprises an expandable tubular stent 10, a porous structure 20 made of a first biodegradable polymer arranged to cover the stent 10, and a micro drug carrier 30 containing a second biodegradable polymer and a drug.

[0043] The stent 10 has a generally cylindrical shape with an inner lumen extending in the axial direction. The stent 10 has a distal end 10A at its distal end and a proximal end 10B at its proximal end.

[0044] As shown in Figures 2 and 3, stent 10 is formed so as to be capable of radial expansion (the state shown in Figure 3) and contraction (the state shown in Figure 2). As shown in Figures 3 and 4, stent 10 has linear rings 11 forming the outer periphery of a cylindrical shape with gaps formed therein, and link portions 12 connecting rings 11 with the gaps.

[0045] As shown in Fig. 4, the wavy ring 11 has a plurality of first strut portions 15 formed by straight lines or curved lines, second strut portions 16 also formed by straight lines or curved lines, and curved portions 17 formed between the first strut portions 15 and the second strut portions 16. Also, as shown in Fig. 4, the ring 11 has a plurality of third strut portions 14 formed by straight lines or curved lines that are adjacent to one side in the axial direction (for example, the left side in Fig. 4) of the link portion 12 and that are arranged in pairs in the circumferential direction (up and down in Fig. 4).

[0046] The rings 11 are arranged in sequence along the axial direction, and adjacent rings 11 in the axial direction are integrated together by link portions 12. Therefore, by increasing or decreasing the number of rings 11, a stent 10 of a desired length can be easily obtained.

[0047] The porous structure 20 having a large number of voids passing therethrough is disposed so as to cover the outer periphery (outer surface 19) of the stent 10, as shown in Figures 3, 4 and 5. The porous structure 20 is configured to be expandable following the expansion of the stent 10, as shown in Figures 2 and 3. By disposing the porous structure 20 on the outer periphery of the stent 10, the stent 10 biases the porous structure 20 against the blood vessel when the stent 10 is expanded within the blood vessel, thereby reducing breakage of the porous structure 20 due to the pressure of the blood flowing within the blood vessel.

[0048] The porous structure 20 extends along the axial direction of the stent 10 and has a mesh structure. The gaps in the mesh structure of the porous structure 20 can be configured to be smaller than the gaps between adjacent rings 11. By making the mesh of the porous structure 20 smaller than the gaps between the rings 11 in this manner, it is possible to prevent plaque and thrombus from scattering when the stent 10 is expanded in the lesion. This makes it possible to prevent peripheral embolism caused by plaque and thrombus.

[0049] The porous structure 20 includes, for example, any of knitted fabrics (knits), woven fabrics (braids), and molded articles. When the porous structure 20 is knitted, the porous structure 20 can be configured by, for example, knitted fabric. By configuring the porous structure 20 by knitted fabric, it is possible to suppress the axial shortening of the porous structure 20 accompanying the expansion of the stent 10. Since the knitted fabric itself is a known knitting method, detailed explanations are omitted in this specification. When the porous structure 20 is a woven fabric, the woven fabric is configured by a known weaving method. When the porous structure 20 is a molded article, the porous structure 20 is configured by a cylindrical sheet having regularly arranged voids. The size, shape, and number of the knitted and woven stitches of the porous structure 20 are not particularly limited as long as peripheral embolism during the expansion of the stent 10 can be prevented.

[0050] The thread diameter of the porous structure 20 is not particularly limited, but may be, for example, 20 μm.

[0051] The porous structure 20 is not limited to those formed by knitting. The porous structure 20 can also be formed by, for example, knitting, woven fabric (braid), etc. The size, shape, number, etc. of the stitches of the porous structure 20 are not particularly limited as long as they can prevent peripheral embolism caused by plaque or thrombus when the stent 10 is expanded. The porous structure 20 can be fixed at any location, such as the tip 10A, the base end 10B, and the link portion 12 of the stent 10. There is no particular limit to the method of fixing the porous structure 20 to the stent 10, and any method can be used, such as adhesive fixation using polymers or paraffin, or fixation using mechanical means such as a cable tie, clip, or thread.

[0052] The preferred materials and effects of the indwelling device 100 will be described below.

[0053] The stent 10 is made of carbon fiber, a metal material, or a polymer material. The stent 10 can be preferably made of a metal material or a polymer material. From the viewpoint of further reducing inflammation, the stent 10 is preferably made of a metal material.

[0054] When the stent 10 is made of a metal material, the metal material used is not particularly limited, and metal materials used for metal stents known in the medical field can be used. Specifically, 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-based alloys such as cobalt-chromium (Co-Cr) alloys, etc. are listed. Among stainless steels, SUS316L, which has the best corrosion resistance, is preferred. Among cobalt-based alloys, MP35N, L605, etc. are preferred.

[0055] When the stent 10 is made of a polymer material, the polymer material to be used is not particularly limited, and any polymer material known in the medical field for use in polymer stents (biodegradable stents) can be used. 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.

[0056] The stent 10 can be suitably formed from a material appropriately selected from the above-mentioned materials according to the application site (placement site in the living body), etc. For example, when the stent 10 is formed from a metal material, the metal material has excellent strength, so that the indwelling device 100 can be placed in the lesion for a desired period of time while maintaining a desired tensile strength. On the other hand, when the stent 10 is formed from a polymer material, the polymer material has excellent flexibility, so that the indwelling device 100 exhibits excellent delivery properties to the lesion. Furthermore, the stent 10 disappears due to biodegradation after a predetermined period of time, so that the influence that may be exerted on the living body lumen after treatment is reduced.

[0057] The stent 10 can also be configured as a self-expanding stent. When the stent 10 is configured as a self-expanding stent, it is preferable to use a superelastic alloy such as a nickel-titanium alloy, since it needs to have the ability to return to its original shape. When the indwelling device 100 is a balloon-expanding type, stainless steel is preferable because it is less likely to return to its original shape after expansion. 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.

[0058] The indwelling device 100 is not particularly limited in its specific shape or size, as long as it can be placed in a lesion that has occurred in a lumen in a living body, such as a blood vessel, a bile duct, a trachea, an esophagus, or a urethra. For example, when used in a coronary artery of the heart, the outer diameter of the stent 10 before expansion can be, for example, 1.0 to 3.0 mm. The wall thickness of the stent 10 is, for example, 0.05 to 0.25 mm. The length of the stent 10 is, for example, 5 to 50 mm.

[0059] The manufacturing method of 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.

[0060] The porous structure 20 contains a given first biodegradable polymer, and is preferably composed only of the first biodegradable polymer.

[0061] At least a portion of the micro drug carriers 30 is embedded within the porous structure 20 (see FIG. 6) and / or at least a portion is supported on the outer surface of the porous structure 20 (see FIG. 7).

[0062] As shown in Fig. 6, the micro drug carrier 30 may be entirely or partially embedded in the porous structure 20, but in order to prevent the micro drug carrier 30 from coming off the porous structure 20, it is preferable that most of the micro drug carrier 30 (e.g., a portion occupying 80% or more, preferably 90% or more of the maximum length) is embedded in the porous structure 20, and it is more preferable that the entirety is embedded in the porous structure 20. In this specification, the term "micro drug carrier" includes capsule-shaped substances having internal spaces and solid substances having no internal spaces.

[0063] 7, when the micro drug carriers 30 are to be supported on the outer surface of the porous structure 20, a coating layer 40 can be disposed on the outer surface of the porous structure 20, and the micro drug carriers 30 can be supported via this coating layer 40. The coating layer 40 can be made of, for example, the same material as that used for the porous structure 20.

[0064] In this embodiment, the drug microcarriers 30 include a predetermined second biodegradable polymer and a drug.

[0065] The decomposition time of the porous structure 20 is the same as or shorter than the decomposition time of the micro drug carriers 30 .

[0066] Here, it is known that a porous structure is covered on a metal stent for the purpose of suppressing and preventing peripheral embolism due to the scattering of plaque and thrombus during stent placement (for example, WO2008 / 062414). However, polymer materials generally have a problem that they are more likely to induce inflammation in the tissue of the inner wall of a biological lumen when they come into contact with the inner wall of a biological lumen (such as a blood vessel wall) than metal materials. In contrast, in this embodiment, the decomposition time of the porous structure 20 is equal to or shorter than the decomposition time of the micro-drug carrier 30. That is, the drug contained in the micro-drug carrier 30 continues to be released from the micro-drug carrier 30 until the porous structure 20 is decomposed and disappears. As a result, inflammation can be suppressed or prevented in the tissue of the biological lumen that is in contact with the porous structure 20 when the stent 10 is in an expanded state by the drug released from the micro-drug carrier 30. Therefore, according to this embodiment, it is possible to simultaneously suppress and prevent peripheral embolism, and reduce and eliminate the risk of inflammation of tissue in a biological lumen due to contact with the porous structure 20.

[0067] The decomposition time of the porous structure 20 and the decomposition time of the micro-drug carrier 30 can be controlled by the type of the first biodegradable polymer that constitutes the porous structure 20 and the second biodegradable polymer that constitutes the micro-drug carrier 30, the size and shape of the porous structure 20 and the micro-drug carrier 30, etc., but are preferably controlled by the first biodegradable polymer that constitutes the porous structure 20 and the second biodegradable polymer that constitutes the micro-drug carrier 30.

[0068] That is, the degradation time of the first biodegradable polymer is the same as or shorter than the degradation time of the second biodegradable polymer. In addition, when the porous structure 20 is substantially composed of the first biodegradable polymer (e.g., more than 90 mass%, preferably more than 95 mass%, preferably more than 99 mass% relative to the total mass of the porous structure 20) or is composed of the first biodegradable polymer (100 mass% relative to the total mass of the porous structure 20), the degradation time of the porous structure 20 can be the same as the degradation time of the first biodegradable polymer. Similarly, when the components (excluding the drug) of the micro drug carrier 30 are substantially the second biodegradable polymer (e.g., greater than 90% by weight, preferably greater than 95% by weight, preferably greater than 99% by weight, based on the total weight of the micro drug carrier 30 (excluding the drug)), or when the micro drug carrier 30 is composed only of the second biodegradable polymer and the drug, the degradation time of the micro drug carrier 30 may be the same as the degradation time of the second biodegradable polymer.

[0069] In this specification, the "degradation time" of the porous structure 20, the micro drug carrier 30, the first biodegradable polymer, and the second biodegradable polymer is a value measured according to the method described below.

[0070] The porous structure 20, the micro drug carrier 30, the granular first biodegradable polymer having a diameter of 2.5 μm, and the granular second biodegradable polymer having a diameter of 2.5 μm (collectively referred to as "sample") are each weighed out in an amount of 3 g. Phosphate buffered saline (PBS) is used as a simulated body fluid. The samples are each immersed in PBS at 37°C (start of experiment). Every hour, the color and transparency of the particles of each sample, the visibility of the particle outline, and the number of visible particles are visually observed, and the time when the sample cannot be seen in the PBS is regarded as the end of degradation, and the time from the start of the experiment to the end of degradation is defined as the degradation time. The time when the sample cannot be seen in the PBS can be quantitatively expressed as the time when the number average molecular weight of the biodegradable polymer becomes less than 2,000. (preferably less than 100), that is, the time when the number average molecular weight of the biodegradable polymer becomes less than 2,000 can be regarded as the end of decomposition (as a quantitative standard for decomposition disappearance). For this reason, the number average molecular weight of the biodegradable polymer in the sample can be measured over time (for example, every hour or every five hours), and the time when it becomes less than 2,000 can be regarded as the end of decomposition, and the time from the start of the experiment to the end of decomposition can be defined as the decomposition time. Note that, in the in-vivo indwelling device 100, the period during which the first biodegradable polymer constituting the porous structure 20 and the polymer constituting the coating layer 40 are decomposed and disappeared, that is, the above number average molecular weight becomes less than 2,000, is preferably 3 months or more and 4 months or less.

[0071] The first biodegradable polymer and the second biodegradable polymer in this embodiment are not particularly limited, and known biodegradable polymers such as those described in JP-T-2011-528275, JP-T-2008-514719, WO 2008 / 1952, JP-T-2004-509205, etc. can be used.

[0072] Specifically, examples of the polymer include: (1) a polymer selected from the group consisting of aliphatic polyesters, polyesters, polyanhydrides, polyorthoesters, polycarbonates, polyphosphazenes, polyphosphates, polyvinyl alcohols, polypeptides, polysaccharides, proteins, and cellulose; and (2) a copolymer composed of two or more types of monomers constituting the above (1). Here, the aliphatic polyester is not particularly limited, and examples thereof include 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. In addition, the polycarbonate is not particularly limited, and examples thereof include tyrosine-derived polycarbonate.

[0073] Alternatively, the first biodegradable polymer and the second biodegradable polymer may be copolymers in which the monomers constituting the polymers are arbitrarily copolymerized. Here, the copolymer is not particularly limited. Specific examples include PDLLA-PCL, PLLA-r-PCL, PLLA-b-PCL, PLLA-r-PTMC (TMC=trimethylene carbonate), PLLA-r-PDTC (DCT=2,2-dimethyltrimethylene carbonate), PLLA-b-PTMC, PLLA-b-PDTC, PLGA (poly(lactide-co-glycolide), polyanhydride, polyorthoester, poly(N-(2-hydroxypropyl)methacrylamide), DLPLA-poly(dl-lactide), LPLA-poly(l-lactide), PGA-polyglycolide, PDO-poly(dioxanone), PGA-TMC-poly(glycolide-co-trimethylene carbonate ... Examples of such polymers include PGA-LPLA-poly(l-lactide-co-glycolide), PGA-DLPLA-poly(dl-lactide-co-glycolide), LPLA-DLPLA-poly(l-lactide-co-dl-lactide), and PDO-PGA-TMC-poly(glycolide-co-trimethylene carbonate-co-dioxanone, and PAE (Polyanhydride esters)-Salicylates in which salicylic acid has been chemically introduced into the polymer backbone (e.g., polymers in which salicylic acid is bound to both ends of polylactide anhydride or polyadipic acid).

[0074] The above polymers and copolymers may be used alone, or in combination of two or more, or in combination of one or more polymers and one or more copolymers. The above polymers and copolymers may be produced by synthesis or may be commercially available. There is no particular limitation on the synthesis method, and known methods can be applied 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 selecting a required structure from L-lactic acid, D-lactic acid, and glycolic acid as raw materials and subjecting them to dehydration polycondensation. They can also be obtained by selecting a required structure from lactide, which is a cyclic dimer of lactic acid, and glycolide, which is a cyclic dimer of glycolic acid, and subjecting them to ring-opening polymerization. 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.

[0075] Of these, the first biodegradable polymer and the second biodegradable polymer are preferably selected from the group consisting of homopolymers of one type of monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or copolymers of two or more types of monomers.

[0076] In one embodiment of the present invention, the decomposition time of the porous structure 20 is substantially the same as the decomposition time of the micro drug carrier 30. With this configuration, the micro drug carrier 30 is decomposed and disappeared around the time when the porous structure 20 is decomposed and disappeared. Therefore, the drug is continuously released from the micro drug carrier 30 to the tissue with which the porous structure 20 is in contact for most of the time during which the porous structure 20 exists. Therefore, with this configuration, it is possible to simultaneously suppress and prevent peripheral embolism and reduce and eliminate the risk of inflammation of the tissue due to contact with the porous structure 20. Here, "the decomposition time of the porous structure 20 is substantially the same as the decomposition time of the micro drug carrier 30" means that the difference between the decomposition time of the porous structure 20 and the decomposition time of the micro drug carrier 30 is within 2 hours, preferably 1 hour. Particularly preferably, the decomposition time of the porous structure 20 is the same as the decomposition time of the micro drug carrier 30.

[0077] In the above embodiment, the decomposition time of the porous structure 20 and the micro drug carriers 30 is, for example, 2 to 6 months, and preferably 3 to 4 months. With such a decomposition time, the porous structure 20 can suppress the scattering of plaque or thrombus when the stent 10 is placed, while an endothelial cell layer can be sufficiently formed on the stent 10.

[0078] In the above embodiment, the porous structure 20 and the micro drug carrier 30 preferably contain the same biodegradable polymer, and more preferably, the biodegradable polymers used in the porous structure 20 and the micro drug carrier 30 are the same. This makes it easy to adjust the decomposition time to be substantially the same. That is, the first biodegradable polymer and the second biodegradable polymer are preferably the same polymer. Specific examples of the first biodegradable polymer and the second biodegradable polymer are the same as those of the biodegradable polymers exemplified above. Of these, the first biodegradable polymer and the second biodegradable polymer are preferably selected from the group consisting of homopolymers of one type of monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or copolymers of two or more types of monomers. That is, in a preferred embodiment of the present invention, the first biodegradable polymer and the second biodegradable polymer are the same polymer, and the first biodegradable polymer and the second biodegradable polymer are selected from the group consisting of homopolymers of one monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or copolymers of two or more monomers.

[0079] The weight-average molecular weight of the first biodegradable polymer and the second biodegradable polymer is not particularly limited and is appropriately selected according to the desired decomposition time (biodegradation rate). Specifically, the weight-average molecular weight of the first biodegradable polymer and the second biodegradable polymer is preferably 10,000 or more, more preferably 10,000 to 1,000,000, and even more preferably 20,000 to 500,000. The method for measuring the weight-average molecular weight includes 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 substance.

[0080] In another embodiment of the present invention, the decomposition time of the porous structure 20 is shorter than the decomposition time of the micro drug carriers 30. With this configuration, the porous structure 20 decomposes and disappears, leaving only the stent 10, and then the micro drug carriers 30 decompose and disappear. Therefore, while the porous structure 20 exists, the drug continues to be released from the micro drug carriers 30 to the tissue with which the porous structure 20 comes into contact. Therefore, with this configuration, it is possible to simultaneously suppress and prevent peripheral embolism and reduce and eliminate the risk of inflammation of tissue due to contact with the porous structure 20.

[0081] Here, the difference between the decomposition time of the porous structure 20 and the decomposition time of the micro drug carriers 30 is 2 hours or more, and preferably 3 hours or more. Such a difference can achieve a better balance between the suppression and prevention of peripheral embolism and the reduction and elimination of the risk of inflammation of tissues due to contact with the porous structure 20.

[0082] In the above other embodiment, the decomposition time of the porous structure 20 is preferably within 4 months, more preferably 2 months or more and 4 months or less, and particularly preferably 3 months or more and 4 months or less. The decomposition time of the micro drug carrier 30 is preferably more than 4 months, more preferably more than 4 months and 12 months or less, and particularly preferably more than 4 months and 6 months or less. With such a decomposition time, the porous structure 20 can suppress the scattering of plaque or thrombus when the stent 10 is placed, while an endothelial cell layer can be sufficiently formed on the stent 10.

[0083] In the other embodiment, the first biodegradable polymer constituting the porous structure 20 and the second biodegradable polymer constituting the micro drug carrier 30 may be a combination of materials such that the decomposition time of the porous structure 20 is shorter than the decomposition time of the micro drug carrier 30. The first biodegradable polymer and the second biodegradable polymer can be the same polymers as those exemplified in the above embodiment. Among them, when a structural unit derived from glycolic acid or caprolactone is introduced, the decomposition rate generally increases. For this reason, it is preferable to use a biodegradable polymer with a relatively fast biodegradation rate for the porous structure 20, such as polyglycolic acid, polycaprolactone, glycolic acid-lactic acid copolymer containing 10 mol % or more of glycolic acid based on the total monomers, glycolic acid-ε-caprolactone copolymer containing 4 mol % or more of caprolactone based on the total monomers, or ε-caprolactone-lactic acid copolymer containing 4 mol % or more of caprolactone based on the total monomers. That is, the first biodegradable polymer is preferably at least one selected from the group consisting of polyglycolic acid, polycaprolactone, glycolic acid-lactic acid copolymer, ε-caprolactone-lactic acid copolymer, and glycolic acid-ε-caprolactone copolymer. Also, it is preferable to use a biodegradable polymer having many structural units derived from lactic acid, such as polylactic acid, a lactic acid-glycolic acid copolymer containing lactic acid in 90 mol % or more of the total monomers, or a lactic acid-ε-caprolactone copolymer containing lactic acid in 96 mol % or more of the total monomers, for the micro drug carrier 30. That is, the second biodegradable polymer is preferably at least one selected from the group consisting of polylactic acid, a lactic acid-ε-caprolactone copolymer, and a lactic acid-glycolic acid copolymer.

[0084] As described above, the first biodegradable polymer and the second biodegradable polymer are different polymers, and it is preferred that the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polycaprolactone, glycolic acid-lactic acid copolymer, ε-caprolactone-lactic acid copolymer, and glycolic acid-ε-caprolactone copolymer, and the second biodegradable polymer is at least one selected from the group consisting of polylactic acid, lactic acid-ε-caprolactone copolymer, and lactic acid-glycolic acid copolymer.

[0085] In addition to the above combination of materials, the following method can also be used to adjust the decomposition time of the porous structure 20 to be shorter than the decomposition time of the micro drug carriers 30.

[0086] For example, methods for controlling the decomposition time of the porous structure 20 include a method of controlling the composition (e.g., glass transition temperature), molecular weight (e.g., length of the thread constituting the porous structure 20), and crystallinity (e.g., spinning conditions for the porous structure 20, presence or absence of annealing) of the first biodegradable polymer, a method of appropriately selecting the presence or absence of terminal treatment (for example, the decomposition time will be longer when terminal treatment is performed by esterification), a method of using an additive, etc. Among these, from the viewpoint of ease of control of the decomposition time, a method of controlling the molecular weight and composition (glass transition temperature) of the first biodegradable polymer is preferably used.

[0087] In addition, the method of controlling the decomposition time of the micro-drug carrier 30 includes a method of controlling the molecular weight and composition of the second biodegradable polymer, the compounding ratio of the drug, and the mixing ratio and mixing method of the second biodegradable polymer and the drug, a method of using an additive, and a method of controlling the shape of the drug. Among these, from the viewpoint of ease of control of the decomposition time of the micro-drug carrier 30 (second biodegradable polymer), a method of controlling the molecular weight and composition of the second biodegradable polymer, the compounding ratio of the drug, and the mixing ratio and mixing method of the second biodegradable polymer and the drug is preferably used. Usually, the biodegradation rate slows down when the molecular weight (weight average molecular weight) of the biodegradable polymer increases. For this reason, a method of adjusting the molecular weight (weight average molecular weight) of the first biodegradable polymer used in the porous structure 20 to be smaller than the molecular weight (weight average molecular weight) of the second biodegradable polymer used in the micro-drug carrier 30 can be used.

[0088] For example, the molecular weight (weight average molecular weight) of the first biodegradable polymer is preferably 20,000 or more, more preferably 50,000 or more and 400,000 or less, and the molecular weight (weight average molecular weight) of the second biodegradable polymer is preferably 500,000 or less, more preferably 50,000 or more and 400,000 or less.

[0089] Alternatively, the porous structure 20 may contain a biodegradable polymer that has been irradiated with an electron beam in advance. In general, when a (co)polymer is irradiated with an electron beam, bonds within the (co)polymer are more likely to be broken, and the biodegradation rate increases. Therefore, even when biodegradable polymers of the same composition are used, the decomposition time can be adjusted by irradiating the biodegradable polymer used in the porous structure 20 with an electron beam in advance.

[0090] 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 deliverability to the lesion and irritation to the blood vessel wall. Preferably, the porous structure 20 is disposed so as to cover the entire outer surface of the stent 10.

[0091] The thickness of the porous structure 20 (outer diameter of the wire portion) is not particularly limited and is set within a range that does not significantly impair the performance of the stent 10, such as the deliverability to the lesion and the irritability to the blood vessel wall. Specifically, the thickness of the porous structure 20 is preferably 1 μm to 100 μm, more preferably 5 μm to 50 μm. The above thickness can more effectively suppress and prevent peripheral embolism associated with the scattering of plaque and thrombus during or after the placement of the stent 10. In addition, the function related to the thickness of the porous structure 20 is preferably thin within a range in which mechanical strength is maintained. A thin porous structure 20 is advantageous in terms of preventing the foldability and device profile from becoming large and improving the passage through the lesion. In other words, if the porous structure 20 is formed too thick, it is disadvantageous in terms of the foldability and device profile, and the inner diameter (expanded diameter) of the stent becomes small after placement in the lesion, reducing the effect of improving blood flow. As a result, it is believed that thrombus adhesion is more likely to occur.

[0092] As for the method of producing the porous structure 20 and the method of covering the stent 10 with the porous structure 20, the methods described in, for example, International Publication No. 2008 / 062414 can be applied in the same manner or with appropriate modifications.

[0093] The shape of the micro drug carrier 30 is not particularly limited, but may be granular, needle-like, pyramidal, cylindrical, rectangular tube, truncated cone, or truncated pyramidal, etc. Among these, the micro drug carrier 30 is preferably granular, needle-like, or pyramidal.

[0094] The size of the micro drug carrier 30 is set within a range that satisfies the effect of drug release. For example, when the micro drug carrier 30 is granular, the average diameter of the micro drug carrier 30 is preferably 1 μm or more and 5 μm or less, more preferably 2 μm or more and less than 4 μm, and particularly preferably more than 2.0 μm and 3.0 μm or less. The above sizes allow a sufficient amount of drug to be retained and released.

[0095] The micro drug carrier 30 includes a second biodegradable polymer and a drug. Here, the drug included in the micro drug carrier 30 is not particularly limited and can be appropriately selected depending on the desired application. Considering the inflammation induced by the porous structure 20, the drug preferably includes an anti-inflammatory agent.

[0096] 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, the anti-inflammatory agent may be alclofenac, alclometasone dipropionate, algestone acetonide, alpha amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anilorac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelain, broperamol, budesonide, carprofen, cycloprofen, synthazone, criprofen, clobeta propionate, zole, clobetasone butyrate, clopirac, cloticasone propionate, cormetasone acetate, cortodoxone, deflazacort, desonide, desoximetasone, dexamethasone, dexamethasone dipropionate, diclofenac potassium, diclofenac sodium, diflorasone diacetate, diflumidone sodium, diflunisal, difluprednate, diphthalone, dimethylsulfoxide, drocinonide, endolisone, enlimomab, enolicam sodium, epirizole, etodolac, etofena Mate, Felbinac, Fenamol, Fenbufen, Fenclofenac, Fenclorac, Fendozar, Fenpiparone, Fentiazac, Flazaron, Fluazacort, Flufenamic acid, Flumizole, Flunisolide acetate, Flunixin, Flunixin meglumine, Fluocortin butyl, Fluorometholone acetate, Fluquazone, Flurbiprofen, Fluretofen, Fluticasone propionate, Furaprofen, Flobufen, Halcinonide, Halobetasol propionate, Ha acetate Lopredone, Ibufenac, Ibuprofen, Ibuprofen Aluminum, Ibuprofen Piconol, Ilonidap, Indomethacin, Indomethacin Sodium, Indoprofen, Indoxol, Intrazol, Isoflupredone Acetate, Isoxepac, Isoxicam, Ketoprofen, Lofemizole Hydrochloride, Lomoxicam, Loteprednol Etabonate, Meclofenamate Sodium, Meclofenamic Acid, Meclorisone 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, preferon, prodolic acid, proquazone, proxazole, proxazole citrate, rimexolone, romazarit, sarcorex, salnacedin, salsale ate, 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, co-drugs thereof, etc. The above anti-inflammatory agents may be used alone or in combination of two or more.

[0097] Here, the content (ratio) of the drug in the micro drug carrier 30 is not particularly limited as long as it is an amount that exerts the desired medicinal effect, but from the viewpoint of further exerting the anti-inflammatory effect, it is preferable to contain a large amount of drug. Specifically, the content of the drug in the micro drug carrier 30 is preferably 30% by mass or more and 60% by mass or less, more preferably 40% by mass or more and 55% by mass or less, based on the total amount (100% by mass) of the second biodegradable polymer and the drug. With this composition, an appropriate amount of the drug can be effectively released for a predetermined period of time.

[0098] Furthermore, the micro drug carrier 30 may contain other drugs in addition to the anti-inflammatory drug. When the micro drug carrier 30 further contains other drugs, the other drugs are not particularly limited, but are preferably drugs that suppress stenosis and blockage of the vascular system that may occur when the stent 10 is placed in the lesion. Specifically, anticancer drugs such as paclitaxel, docetaxel, vinblastine, vindesine, irinotecan, and pirarubicin; immunosuppressants such as sirolimus, everolimus, pimecrolimus, and sirolimus derivatives such as ABT-578, tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, and gusperimus; antibiotics such as mitomycin, adriamycin, doxorubicin, actinomycin, daunorubicin, idarubicin, pirarubicin, aclarubicin, epirubicin, and zinostatin stimalamer; antithrombotic drugs such as aspirin and ticlopidine; cerivastatin, cerivastatin sodium, atorvastatin, pitavastatin, fluvastatin, and fluvastatin sodium Examples of the other drugs include HMG-CoA reductase inhibitors such as quinapril, trandolapril, temocapril, delapril, enalapril maleate, and captopril; calcium antagonists such as hifedipine, nilvadipine, benidipine, and nisoldipine; antihyperlipidemic drugs such as probucol; integrin inhibitors such as AJM300; antiallergic drugs 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, and clopidogrel. These drugs are preferred in that they can control the behavior of cells in the affected tissue to treat the affected area. The other drugs may be used alone or in combination of two or more.

[0099] Instead of or in addition to the other drugs, the micro drug carrier 30 preferably contains an adhesion enhancer. With this configuration, when the stent 10 is placed at a desired site, the micro drug carrier 30 adheres more strongly to the tissue at the placement site of the stent 10, allowing the drug effect to act more effectively on the tissue.

[0100] When the micro drug carrier 30 contains an adhesion improver, examples of the adhesion improver include sterol (e.g., cholesterol), lipid, phospholipid, fat, fatty acid, surfactant, and derivatives thereof. The above adhesion improvers may be used alone or in combination of two or more. Among these, a combination of sterol and fatty acid or phospholipid is preferable. From the viewpoint of homogeneity, the adhesion improver preferably contains cholesterol and fatty acid or phospholipid, and more preferably is composed only of cholesterol and fatty acid or phospholipid. In this case, the cholesterol may be cholesterol or a chemically modified cholesterol or cholesterol conjugate. The cholesterol may be dimethylaminoethane-carbamoyl cholesterol (DC-cholesterol). That is, the micro drug carrier 30 preferably further contains sterol and fatty acid or phospholipid. More preferably, the micro drug carrier 30 further contains cholesterol and fatty acid or phospholipid. When the micro-drug carrier 30 further comprises a sterol and a fatty acid or a phospholipid, the sterol and the fatty acid or the phospholipid may be mixed with the second biodegradable polymer and the drug, or coated on the mixture of the second biodegradable polymer and the drug, with the latter being preferred. That is, the micro-drug carrier 30 is preferably coated with an adhesion improver comprising a sterol and a fatty acid or a phospholipid. The micro-drug carrier 30 is more preferably coated with an adhesion improver comprising a cholesterol and a fatty acid or a phospholipid. The micro-drug carrier 30 is particularly preferably coated with an adhesion improver comprised of a cholesterol and a fatty acid or a phospholipid.

[0101] When the adhesion improver contains a fatty acid, examples of the fatty acid include lauric acid, lauroleic acid, tetradeadienoic acid, octanoic acid, myristic acid, myristoleic acid, decenoic acid, decanoic acid, hexadecenoic acid, palmitoleic acid, palmitic acid, linoleic acid, linoleic acid, oleic acid, vaccenic acid, stearic acid, eicosapentaenoic acid, arachidonic acid, mead acid, arachidic acid, docosahexaenoic acid, docosapentaenoic acid, docosatetraenoic acid, docosenoic acid, tetracosanoic acid, hexacosanoic acid, pristanic acid, phytanic acid, and nervonic acid. The above fatty acids may be used alone or in combination of two or more.

[0102] In the case where the adhesion promoter contains a phospholipid, the phospholipid may be, for example, a phospholipid commonly found in serum or cell membranes, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol; dieicosenoylphosphatidylcholine (1,2-dieicosenoyl-sn-glycero-3-phosphocholine, C20:1 PC), diarachidonoylphosphatidylcholine (1,2-diarachidoyl-sn-glycero-3-phosphocholine, C20:1 PC), dierucoylphosphatidylcholine (1,2-dierucoyl-sn-glycero-3-phosphocholine, C22:1 PC), didocosahexaenoylphosphatidylcholine (1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine, C22:6 PC), diac ... Examples of phospholipids include phospholipids having an acyl chain length of about 20 to about 34 carbons, such as 1,2-henicosenoyl-sn-glycero-3-phosphocholine (C21:1 PC), henicosenoylphosphatidylcholine (1,2-henicosenoyl-sn-glycero-3-phosphocholine, C24:1 PC), and dinervonylphosphatidylcholine (1,2-dinervonyl-sn-glycero-3-phosphocholine, C24:1 PC). The above phospholipids may be used alone or in combination of two or more.

[0103] The composition of the adhesion improver is not particularly limited and is appropriately selected according to the desired tissue adhesion. For example, when the adhesion improver contains sterol (particularly cholesterol) and fatty acid, the mixing ratio of sterol to fatty acid (mass ratio of sterol: fatty acid) is, for example, about 1:2 to about 3:1, preferably 1:1.5 to 2.5:1, more preferably 1:1 to 2:1. For example, when the adhesion improver contains sterol (particularly cholesterol) and phospholipid, the mixing ratio of sterol to phospholipid (mass ratio of sterol: phospholipid) is, for example, about 1:2 to about 3:1, preferably 1:1.5 to 2.5:1, more preferably 1:1 to 2:1.

[0104] In this embodiment, the living body indwelling device 10 may preferably adopt a configuration in which the coating layer 40 contains an adhesion improver in a form (form shown in FIG. 7) that includes the micro drug carrier 30. When the living body indwelling device 10 is configured in this way, the content of the adhesion improver is not particularly limited and is appropriately selected according to the desired biological tissue adhesiveness. As an example, in a form in which the coating layer 40 contains an adhesion improver, the micro drug carrier 30 is 10% by mass or more and 75% by mass or less, preferably 20% by mass or more and 65% by mass or less, and more preferably 30% by mass or more and 55% by mass or less, relative to the coating layer 40 (100% by mass). The coating layer 40 containing the adhesion improver may be adjusted to an amount that can cover the entire surface of the micro drug carrier 30. With this composition, the micro drug carrier 30 can be more effectively adhered to the biological tissue (the biological tissue located at the placement target site).

[0105] The method for producing the micro drug carrier 30 is not particularly limited, and for example, a method can be used in which the second biodegradable polymer and drug, and if necessary, at least one of a solvent, another drug, and an adhesion promoter (e.g., a mixture of a sterol and a fatty acid or a phospholipid), are mixed and molded into a suitable shape. Alternatively, a method can be used in which the second biodegradable polymer and drug, and if necessary, at least one of a solvent and another drug are mixed and molded into a suitable shape (molded product), and then the molded product is coated with a mixture of an adhesion promoter (e.g., a mixture of a sterol and a fatty acid or a phospholipid) and, if necessary, a solvent, to form a coating of the adhesion promoter on the molded product.

[0106] As described above, the biological indwelling device 100 of this embodiment is a biological indwelling device comprising an expandable tubular stent 10, a porous structure 20 made of a first biodegradable polymer arranged to cover the stent 10, and a micro-drug carrier 30 containing a second biodegradable polymer and a drug, wherein at least a portion of the micro-drug carrier 30 is embedded within the porous structure 20 and / or at least a portion is supported on the outer surface of the porous structure 20, and the decomposition time of the porous structure 20 is substantially the same as or shorter than the decomposition time of the micro-drug carrier 30.

[0107] According to the indwelling device 100 configured as described above, the porous structure 20 decomposes and disappears after a certain period of time has elapsed since placement, and the drug continues to be released from the drug microcarriers 30 until the porous structure 20 decomposes and disappears. Therefore, the indwelling device 100 can effectively suppress the onset of inflammation caused by the porous structure 20 while preventing the scattering of plaque or thrombus when the stent 10 is expanded. [Explanation of symbols]

[0108] 10 Stents 11. Ring 12 Link section 20 Porous structure 30 Micro drug carrier 40 Coating Layer 100 Living body specimens

Claims

1. A living body indwelling device comprising an expandable cylindrical stent, a porous structure made of a first biodegradable polymer arranged so as to cover the stent, and a micro drug carrier containing a second biodegradable polymer and a drug, The micro drug carrier is at least partially embedded in the porous structure and / or at least partially supported on the outer surface of the porous structure; A living body indwelling device, wherein the decomposition time of the porous structure is substantially the same as or shorter than the decomposition time of the micro drug carrier.

2. the first biodegradable polymer and the second biodegradable polymer are the same polymer; 2. The indwelling device according to claim 1, wherein the first biodegradable polymer and the second biodegradable polymer are selected from the group consisting of homopolymers of one type of monomer selected from the group consisting of lactic acid, caprolactone, glycolic acid, dioxanone, butyrolactone, valerolactone, hydroxybutyric acid, and trimethylene carbonate, or copolymers of two or more types of monomers.

3. the first biodegradable polymer and the second biodegradable polymer are different polymers; the first biodegradable polymer is at least one selected from the group consisting of polyglycolic acid, polycaprolactone, glycolic acid-lactic acid copolymer, ε-caprolactone-lactic acid copolymer, and glycolic acid-ε-caprolactone copolymer; 2. The indwelling device according to claim 1, wherein the second biodegradable polymer is at least one selected from the group consisting of polylactic acid, lactic acid-ε-caprolactone copolymer, and lactic acid-glycolic acid copolymer.

4. 4. The indwelling device according to claim 3, wherein the molecular weight of the first biodegradable polymer and the second biodegradable polymer is 20,000 or more and 500,000 or less.

5. 5. The indwelling device according to claim 3, wherein the decomposition time of said porous structure is within 4 months.

6. The indwelling body of claim 5, wherein the decomposition time of the micro drug carrier is more than 4 months.

7. 2. The indwelling device according to claim 1, wherein the number average molecular weight of said porous structure and said micro drug carrier in a decomposed state is less than 2,000.

8. The living body indwelling device according to claim 1, wherein the micro drug carriers are granular, needle-like, or pyramidal.

9. The indwelling device according to claim 1, wherein the micro drug carrier further comprises a sterol, and a fatty acid or a phospholipid.

10. The indwelling device according to claim 1 , wherein the stent is made of a metal material or a polymer material.

11. The indwelling body according to claim 1 , wherein the drug includes an anti-inflammatory agent.

12. 2. The indwelling device according to claim 1, wherein the ratio of the drug in the drug-carrying microcarrier is 40% by mass or more and 55% by mass or less based on the total amount of the second biodegradable polymer and the drug.

13. The porous structure includes a coating layer containing the micro drug carrier, 2. The indwelling device according to claim 1, wherein said coating layer contains an adhesion promoter for adhering said micro drug carriers to biological tissue.

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