In-vivo indwelling stent and stent delivery system

Abstract

An in-vivo indwelling stent 1 has a drug-containing coating portion on an outer surface, is self-expanding, and comprises: a ring-shaped body 2 provided with multiple bent portions 21, 22 with vertices on one end and an other end; and connecting portions 31, 32 connecting the multiple bent portions 21, 22. Apexes of adjacent bent portions are offset by a predetermined distance in a circumferential direction of a stent body. A distance (D1) between the apexes of adjacent bent portions is 0.485 mm or less, and the relationship between a circumferential distance Y of a stent body 10 and an axial distance X between the apexes of the bent portions satisfies the following Formula (I).　(I): Y ≥ -0.0028X2 - 0.2927X + 358.87

Description

Intravascular stent and stent delivery system

[0001] The present invention relates to an intravascular stent used for treating stenotic or occluded portions that occur in lumens of blood vessels, bile ducts, tracheas, esophaguses, urethras, and other organs. Particularly, it relates to a drug-eluting stent (DES).

[0002] A stent is a medical device consisting of a cylindrical body with an opening on its side, composed of multiple annular bodies made of wavy struts with curved sections, arranged axially, with adjacent annular bodies integrated via connecting sections. For example, it is used to prevent restenosis after percutaneous coronary angioplasty for myocardial infarction or angina pectoris. Many self-expanding stents used for in vivo placement are cylindrical in shape, can be reduced in diameter by compression in the central axial direction, and can be restored to their original shape by releasing the compression. The stent body of a self-expanding in vivo placement stent is made of annular bodies formed of wavy linear components with multiple bent sections having vertices at one end and the other end in the axial direction, and connecting sections that connect the annular bodies when the multiple annular bodies are arranged axially within the stent body. The application of so-called bare-metal stents, which are not coated with a drug, results in a lower restenosis rate compared to PTCA or PCI without stents, but restenosis is still observed in approximately 20-30% of cases at the stent placement site. The main cause of restenosis is intimal thickening due to the migration and proliferation of vascular smooth muscle cells. Therefore, drug-eluting stents have been proposed, which prevent restenosis by coating the outer surface of the stent with a drug that can suppress the migration and proliferation of vascular smooth muscle cells and releasing the drug at the stent placement site. Drugs used include taxol (paclitaxel), mitomycin C, adriamycin, genistein, tylfostine, cytochalasin, and sirolimus (rapamycin). In self-expanding stents, a drug-containing coating is provided by coating the outer surface of the expanded stent body with a drug-containing solution. For coating, a coating solution in which the drug and a biocompatible polymer are dissolved in a solvent is used, and it is applied to the stent body so that a predetermined amount of drug is present on the outer surface of the stent.When using a self-expanding stent body that includes an annular body formed from a wavy linear component having multiple bent portions with vertices at one end and the other end in the axial direction as described above, and connecting portions that connect the annular bodies when the multiple annular bodies are arranged in the axial direction of the stent body, the above-mentioned coating liquid is applied to the expanded stent body.

[0003] Japanese Patent Publication No. 2019-195673 (WO2016-163339)

[0004] In recent years, there has been an increase in cases of stenosis due to calcification in the arteries of the lower extremities. To improve stenosis caused by calcification in the arteries of the lower extremities, such as the superficial femoral artery (SFA), and to suppress restenosis after improvement, it is desirable to have a drug coating layer over the entire outer surface of the stent, including the curved portion. However, stents using a self-expanding stent body, such as the one shown in Patent Document 1, have curved portions at adjacent free ends in the axial direction. When a drug coating is applied to such a type of stent body, a thin film of drug may be formed connecting the curved portions of the adjacent free ends.

[0005] The object of the present invention is to provide a self-expanding in vivo stent having a drug-containing coating, and furthermore, an in vivo stent and stent delivery system that reduces the formation of a thin drug film connecting adjacent free end bends, even if the stent has axially adjacent free end bends.

[0006] The following is a stent for implantation in a living body that achieves the above objective, comprising a tubular stent body and a drug-containing coating provided on the outer surface of the stent body, and which can be reduced in diameter by compression in the central axis direction and restored to its pre-reduced shape by releasing the compression, wherein the stent body comprises an annular body formed of a wavy linear component having a plurality of bent portions having vertices on one end and the other end in the axial direction, and a connecting portion that connects the annular bodies when the plurality of annular bodies are arranged in the axial direction of the stent body, wherein between adjacent annular bodies in the axial direction of the implantation in a living body, the vertices of the adjacent bent portions are offset in the circumferential direction of the stent body, and between adjacent annular bodies in the axial direction of the implantation in a living body, except for those between annular bodies located at both ends of the stent body, they are not connected by the connecting portion and are free ends, and have bent portions that are close to each other and facing each other diagonally in the axial direction, Furthermore, when the in vivo implantable stent is uncompressed, the distance (D1) between the vertices of the free ends and adjacent bent portions is 0.485 mm or less, and the distance between the vertices of the bent portions satisfies the following equation (I) in relation to the axial distance X, where Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, the drug-containing coating is provided on the outer surface of the free end and adjacent to the bent portion of the in vivo stent.

[0007] Furthermore, the following is a device that achieves the above objective: a stent delivery system comprising a sheath, the above-mentioned in vivo implantable stent housed within the tip of the sheath, and an inner tube slidably inserted through the sheath for pushing the in vivo implantable stent out from the tip of the sheath.

[0008] The self-expanding in vivo stent of the present invention comprises a tubular stent body and a drug-containing coating provided on the outer surface of the stent body, and is an in vivo stent that can be reduced in diameter by compression in the central axis direction and restored to its pre-reduced shape by releasing the compression. The stent body comprises an annular body formed of a wavy linear component having a plurality of bent portions having vertices on one end and the other end in the axial direction, and a connecting portion that connects the annular bodies when the plurality of annular bodies are arranged in the axial direction of the stent body. Between adjacent annular bodies in the axial direction of the in vivo stent, the vertices of the adjacent bent portions are offset in the circumferential direction of the stent body, and between adjacent annular bodies in the axial direction of the in vivo stent, except for the annular bodies located at both ends of the stent body, they are not connected by the connecting portion and are free ends, and have bent portions that are close to each other and facing each other diagonally in the axial direction. Furthermore, when the in vivo implantable stent is uncompressed, the distance (D1) between the vertices of adjacent bent portions that are free ends is 0.485 mm or less, and the circumferential distance Y of the stent body between the vertices of the bent portions satisfies the following equation (I) in relation to the axial distance X: Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, a drug-containing coating is provided on the outer surface of the free end and adjacent bent portion. When the in vivo implantable stent is uncompressed, the free end and adjacent bent portion satisfy the above-mentioned conditions, and when the drug-containing coating is formed on the outer surface of the stent body when uncompressed, the formation of a thin drug film between the adjacent free end bent portions can be suppressed. In addition, since the distance between the vertices of the free end and adjacent bent portion (D1) is 0.485 mm or less, the implantation site of the stent where the free end and adjacent bent portion are located can be sufficiently expanded and held when uncompressed.

[0009] Figure 1 is an unfolded view of a self-expanding in vivo stent according to an embodiment of the present invention. Figure 2 is an unfolded view of the in vivo stent shown in Figure 1 in a reduced diameter state. Figure 3 is a partially enlarged view of the in vivo stent shown in Figure 1. Figure 4 is a partially enlarged view of the in vivo stent shown in Figure 1. Figure 5 is an unfolded view of a self-expanding in vivo stent according to another embodiment of the present invention. Figure 6 is an unfolded view of a self-expanding in vivo stent according to another embodiment of the present invention. Figure 7 is a partially abbreviated front view of a stent delivery system according to an embodiment of the present invention. Figure 8 is a partially abbreviated enlarged cross-sectional view of the area near the tip of the stent delivery system shown in Figure 7. Figure 9 is a partially abbreviated enlarged cross-sectional view of the area near the proximal end of the stent delivery system shown in Figure 7. Figure 10 is an explanatory diagram for explaining the operation of a stent delivery system according to an embodiment of the present invention. Figure 11 is an explanatory diagram for explaining a coating device used to form a drug-containing coating portion in an in vivo stent. Figure 12 is an explanatory diagram for explaining the main part of the coating device shown in Figure 11. Figure 13 is a graph showing the test results of in-vivo stents.

[0010] The in vivo stent of the present invention will be described using the embodiment shown in the drawings. The self-expanding in vivo stent 1 of the present invention comprises a tubular stent body 10 and a drug-containing coating portion 30 provided on the outer surface of the stent body 10, and is an in vivo stent that can be reduced in diameter by compression in the central axis direction and restored to its pre-reduced shape by releasing the compression. The stent body 10 comprises an annular body 2 formed of a wavy linear component having a plurality of bent portions 21, 22 having vertices P1, P2 at one end and the other end in the axial direction, and connecting portions 31, 32 that connect the annular bodies when the plurality of annular bodies 2 are arranged in the axial direction of the stent body 10. Between adjacent annular bodies 2 in the axial direction of the in vivo stent 1, the vertices P1 and P2 of the adjacent bent portions 21 and 22 are offset in the circumferential direction of the stent body 10. Furthermore, between adjacent annular bodies 2 in the axial direction of the in vivo stent 1, except for those between annular bodies located at both ends of the stent body 10, the annular bodies are not connected by a connecting portion and are free ends, and are provided with bent portions 21 and 22 that are close to each other and facing each other diagonally in the axial direction.

[0011] Furthermore, when the in vivo stent 1 is uncompressed (specifically, in the uncompressed, unfolded state shown in Figures 2 and 3), the distance (D1) between the vertices of adjacent bent portions that are free ends is 0.485 mm or less, and the distance between the vertices of the bent portions 21 and 22 satisfies the following equation (I) in relation to the axial distance X, where Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, a drug-containing coating portion 30 is provided on the outer surface of the free ends and adjacent bent portions 21 and 22.

[0012] The in vivo stent 1 of the present invention is a self-expanding in vivo stent 1 that is formed in a cylindrical shape, can be reduced in diameter by compression in the central axis direction, and can be restored to its original shape by releasing the compression.

[0013] In the in vivo stent 1, between adjacent annular bodies 2 in the axial direction, the apex P1 of the bent portion (peak) 21 on one end and the apex P2 of the bent portion (valley) 22 on the other end are offset in the circumferential direction of the stent body 10. Furthermore, in this embodiment, the annular bodies 2 adjacent in the axial direction of the in vivo stent 1, excluding those located at both ends of the stent body 10, are not connected by a connecting portion and are free ends, and are provided with bent portions 21 and 22 that are close to each other and facing each other diagonally in the axial direction. The in vivo stent of the present invention is particularly effective as a stent for the arteries of the lower limbs.

[0014] The self-expanding in vivo stent 1 of this embodiment is formed in a substantially cylindrical shape and comprises a stent body 10 that is reduced in diameter when inserted into a body and can be restored to its pre-reduced shape when implanted in a body, and a drug-containing coating portion 30 provided on its outer surface. As shown in Figures 1 and 2, the stent body 10 comprises a plurality of annular bodies 2 that can deform in a direction in which the outer diameter is reduced when stress is applied, and connecting portions 31 and 32 that connect the plurality of annular bodies 2 in an axial position of the stent. The annular bodies 2 comprise a linear first strut portion 23, a linear second strut portion 24, and a bent portion 21 at one end and a bent portion 22 at the other end that connect adjacent linear first strut portions 23 and linear second strut portions 24. The bent portion 21 at one end and the bent portion 22 at the other end are the parts that deform when the in vivo stent 1 expands or contracts in the radial direction.

[0015] Furthermore, when the stent is reduced in diameter, the linear first strut portion 23 and the linear second strut portion 24 of the annular body 2 become approximately parallel to the central axis of the stent, as shown in Figure 2. The number of bent portions 21 at one end and bent portions 22 at the other end of the annular body 2 of the stent body 10, and the number of vertices P1 (peak) at one end and vertices P2 (valley) at the other end of the annular body 2 are preferably 12 to 20, and particularly preferably 16.

[0016] The connecting portions 31 and 32 extend diagonally with respect to the central axis of the stent body 10, and the connecting portions 31 and 32 are generally straight, with the widths (line widths) of the connecting portions 31 and 32, the struts 23 and 24, and the bent portions being approximately the same. The widths (line widths) of the connecting portions 31 and 32, the struts 23 and 24, and the bent portions are preferably 0.08 mm to 0.120 mm, and particularly preferably 0.10 mm to 0.115 mm.

[0017] Furthermore, the annular body 2 is formed from a wavy linear component having multiple bent portions 21 and 22, each having a vertex at one end and the other end in the axial direction. Between adjacent annular bodies 2 in the axial direction of an in vivo implantable stent, the vertices of the adjacent bent portions 21 and 22 are offset by a predetermined length (specifically, about 0.35 to 0.40 mm) in the circumferential direction of the stent body.

[0018] Furthermore, in the in vivo stent 1 of the present invention, when the stent 1 is uncompressed (specifically, in the uncompressed, deployed state shown in Figures 2 and 3), the distance (D1) between the vertices of adjacent bent portions that are free ends is 0.485 mm or less. This allows for sufficient expansion and retention of the stent implantation site at adjacent bent portions. Preferably, the distance (D1) between the vertices of the bent portions is 0.30 mm or less. Moreover, it is preferable that the distance (D1) between the vertices of adjacent bent portions is 0.10 to 0.24 mm. By doing so, deformation of adjacent bent portions during stent compression is facilitated, and overlapping is suppressed.

[0019] Furthermore, the distance between adjacent free ends and bends (shortest distance, D2) is preferably 0.20 mm or less, and particularly preferably 0.1 to 0.15 mm.

[0020] Furthermore, in the in vivo stent 1 of the present invention, when the stent 1 is uncompressed (specifically, in the uncompressed unfolded state shown in Figures 2 and 3), the circumferential distance Y between the vertices of the bent portions 21 and 22 of the stent body 10 satisfies the following equation (I) in relation to the axial distance X. Note that a drug-containing coating portion 30 is provided on the outer surfaces of the free ends of the adjacent bent portions 21 and 22. Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) The distance between the vertices of the bent portions 21 and 22 was calculated from the results (see Figure 13) obtained by creating a number of stent bodies with different circumferential distances Y and axial distances X of the stent body 10, applying a coating liquid for shaping the drug-containing coating portion to the outer surface of the stent base using a coating apparatus as shown in Figures 11 and 12, and confirming whether or not a drug-containing thin film (crosslinking) connecting the vertices of the bent portions 21 and 22 was formed. The coating apparatus shown in Figures 11 and 12 will be described later. As shown in Figure 13, when the relationship between the circumferential distance Y and axial distance X of the stent body 10 between the vertices of the bent portions 21 and 22 satisfies the above equation (I), the formation of a drug-containing thin film (crosslinking) connecting the vertices of the bent portions 21 and 22 was not observed.

[0021] Furthermore, the axial length of the annular body 2 when it is self-expanding is preferably 1.3 to 1.7 mm, more preferably 1.4 to 1.6 mm, and even more preferably 1.45 to 1.55 mm. The lengths of the connecting parts 31 and 32 are preferably 0.35 to 0.50 mm, more preferably 0.40 to 0.45 mm. In addition, the total axial length of one annular body and the connecting parts connected thereto is preferably 1.5 to 2.5 mm, more preferably 2.0 to 2.2 mm.

[0022] In the in vivo stent 1 of the present invention, the inclination angle of the stent body 10 at the connection portion with respect to the axial direction in the uncompressed view of the in vivo stent is preferably 110 to 130 degrees. Specifically, the inclination angles of the connection portions 31 and 32 with respect to the central axis of the stent body when the annular body 2 is self-expanding (the inclination angles of the stent body with respect to the central axis in the unfolded state of the stent, A1 and A2 in Figure 4) are preferably 115 to 125 degrees. Furthermore, it is preferable that the inclination angle A1 at the connection portion 31 and the inclination angle A2 at the connection portion 32 shown in Figure 4 are approximately the same (specifically, the difference is less than 5%).

[0023] In this embodiment, the stent body 10 has an outer diameter of 4.0 to 10.0 mm during self-expansion, and is particularly preferably 5.0 to 9.0 mm. The axial length of the stent during self-expansion is preferably 30 to 200 mm, particularly preferably 40 to 180 mm, and more preferably 40 to 150 mm. The number of annular bodies 2 in the stent body 10 is preferably 7 to 100, and more preferably 20 to 90.

[0024] In the in vivo stent 1 of the present invention, the ratio of the outer surface area of ​​the stent body 10 to the outer surface area of ​​the virtual cylindrical body of the in vivo stent 1 during self-expansion is preferably 15% to 20%, and particularly preferably 15% to 18%. The virtual cylindrical body of the in vivo stent 1 refers to the cylindrical body formed by the outer diameter and total length of the stent body 10 during self-expansion. Furthermore, the ratio of the outer surface area of ​​the stent body 10 to the outer surface area of ​​the virtual cylindrical body can be calculated as "total outer surface area of ​​the stent body 10 / outer surface area of ​​the virtual cylindrical body (outer surface area of ​​the cylindrical body formed by the outer diameter and total length of the stent body 10 during self-expansion)".

[0025] As shown in Figure 4, the in vivo stent has multiple lateral openings formed within adjacent annular bodies 2 during self-expansion. As shown in Figure 4, the multiple lateral openings formed within adjacent annular bodies 2 during self-expansion are formed by struts 23, struts 24, bent portions 21, 22, and connecting portions 31, 32. The radius (C) of the maximum inscribed circle (B) at each lateral opening is preferably 0.37 to 0.45 mm, and particularly preferably 0.37 to 0.40 mm. The size of the lateral openings is not uniform and varies depending on the location. Also, the radius (C) of the maximum inscribed circle (B) at each lateral opening does not differ significantly, but they are not all the same. It is preferable that the radius (C) of the maximum inscribed circle (B) at each lateral opening is approximately the same, specifically, that the difference is less than 15%, preferably less than 10%.

[0026] Furthermore, it is preferable that the diameter retention rate at the center of the in-vivo stent 1, when the central part of the in-vivo stent is curved with a radius of curvature of R7.5 mm, is 85% or more, and particularly preferably 87% or more. The diameter retention rate at the center of the in-vivo stent when the central part of the in-vivo stent is curved with a radius of curvature of R7.5 mm is calculated by pressing the central part of the in-vivo stent against a cylindrical rod with a radius of curvature of R7.5 mm and pressing down on both sides of the in-vivo stent so that the in-vivo stent is aligned with the cylindrical rod with a radius of curvature of R7.5 mm. In this state, the central part of the in-vivo stent deforms into an elliptical cross-section and has a short-diameter portion. The diameter retention rate (%) is calculated by "length of the short-diameter portion of the central part when deformed / outer diameter of the in-vivo stent when not deformed" × 100.

[0027] Furthermore, the expansion force of the in vivo implantable stent is preferably 9 to 11 N / cm. The above expansion force can be measured with a commercially available radial force measuring instrument. The material forming the stent body 10 is preferably a metal having superelastic properties. Specific examples of alloys having superelastic properties include Ni-Ti alloy (which may also contain Co, Fe, Zr, Hf, Pd, Au, Fe, Pt, Mo), Cu alloy (which may also contain Al, Mn, Ni, Zn), and Mg alloy (which may also contain Li, Al, Zn, Ca, Y, W, Zr, Gd, Mn, Sc, Cu, Ag, Nd, and other rare earth metals).

[0028] As shown in Figure 3, the in vivo stent 1 of the present invention includes a drug-containing coating portion 30 provided on the outer surface of the stent body 10. The drug-containing coating portion 30 includes a linear coating portion 34 that covers the linear first strut portion 23 and the linear second strut portion 24, and a bent portion coating portion 35 that covers the bent portions 21 and 22. The drug-containing coating portion is preferably a drug-eluting coating portion. Furthermore, the drug-containing coating portion is preferably flexible or elastic.

[0029] The in vivo stent 1 of the present invention is a self-expanding type that is compressed in the axial direction when inserted into the body and expands outward to return to its pre-compression shape when implanted in the body. The stent body 10 is formed by cutting a superelastic metal tube to create the basic shape of the stent body, then expanding its diameter, and subsequently heat-treating it, so that the stent body is superelastic in the expanded state. The drug-containing coating portion 30 is applied to the outer surface of the stent body 10 after the diameter has been expanded and either before or after the heat treatment.

[0030] The drug contained in the drug-containing coating portion 30 of the in vivo implantable stent of the present invention is, for example, at least one compound selected from the group consisting of anticancer agents, immunosuppressants (e.g., sirolimus, sirolimus derivatives), antibiotics, antirheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, calcium channel blockers, antihyperlipidemic agents, integrin inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid-improving agents, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet agents, anti-inflammatory agents, bio-derived materials, interferon, and NO production-promoting substances.

[0031] The drug contained in the drug-containing coating of the in vivo implantable stent 1 is preferably sirolimus or a sirolimus derivative. Examples of sirolimus derivatives include everolimus, temsirolimus, ridafololimus, and zotarolimus.

[0032] The drug coating the outer surface of the stent body may be supported on a polymer to form a drug-containing coating. When the drug-containing coating is supported on a polymer, the drug is gradually released after the stent is placed in the body, so the drug effect lasts for a long period of time and restenosis at the stent site is reliably prevented. Furthermore, since residual polymer may cause an inflammatory reaction, it is preferable that the polymer be a biodegradable polymer.

[0033] Biodegradable polymers include, for example, at least one polymer selected from the group consisting of polyester, aliphatic polyester, polyacid anhydride, polyorthoester, polycarbonate, polyphosphazene, polyphosphate ester, polyvinyl alcohol, polypeptide, polysaccharide, protein, and cellulose; copolymers obtained by arbitrarily copolymerizing monomers constituting a polymer; and mixtures of polymers and / or copolymers. Aliphatic polyesters include, for example, polylactic acid (PLA), polyglycolic acid (PGA), lactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), and copolymers of lactic acid and caprolactone. Here, copolymers of lactic acid and caprolactone are preferred. The drug-containing coating portion preferably contains a polymer with a molecular weight of 150,000 or more, and in particular, the above-mentioned biodegradable polymer with a molecular weight of 150,000 or more is preferred.

[0034] Furthermore, a primer coating layer may be placed between the stent body and the drug-containing coating to reduce variations in the ease of peeling of the drug-containing coating on the stent body. As the material for the primer coating layer, for example, a biodegradable polymer material can be used when the drug-containing coating is supported on a polymer.

[0035] Preferably, the drug-containing coating portion 30 has a first coating having a first polymer formed by the auto-oxidative polymerization of dopamine molecules or their analogs on the outer surface of the stent body, a second coating layer having a second polymer covalently bonded to the first polymer on the first coating layer, and a third coating layer having a drug and a third polymer supporting the drug on the second coating layer. Furthermore, it is preferable that the second polymer and the third polymer in the drug-containing coating portion 30 form an interpenetrating polymer network structure.

[0036] Furthermore, as in the stent 1 of this embodiment, it is preferable to provide markers 5 made of radiopaque material. It is preferable to provide the radiopaque material markers 5 at both ends of the stent body 10. In particular, as shown in Figures 1 and 2, it is preferable to provide multiple radiopaque material markers 5 at each end. The radiopaque material markers 5 are fixed to the stent so as to close the small opening formed in the stent. Such markers are preferably attached, for example, by placing a disc-shaped member of an X-ray contrast material having a portion slightly smaller and a portion larger than the small opening formed in the stent body 10, pressing it from both sides, and crimping it in a rivet-like manner.

[0037] Furthermore, in the stent 1 of this embodiment, the connecting portions 31 and 32 include a first pattern connecting portion 31 that extends at a predetermined angle oblique to the central axis of the stent body, and a second pattern connecting portion 32 that extends at a predetermined angle oblique to the central axis of the stent body and in a direction different from that of the first pattern connecting portion 31. The connecting portion between opposing annular bodies 2 is either the first pattern connecting portion 31 or the second pattern connecting portion 32, and is the same pattern connecting portion. The connecting portions adjacent in the axial direction of the stent body are arranged so that the first pattern connecting portion 31 and the second pattern connecting portion 32 alternate.

[0038] Furthermore, in the in vivo implantable stent 1 of the present invention, the stent body 10 further comprises two maximum connection portion holders 11 having connection portions between all adjacent vertices of adjacent annular bodies 2 at both ends of the stent body, two first diminished connection portion holders 12 having 40 to 60% of the number of connection portions between the annular body 2 having the maximum connection portion holders and the annular body 2 located axially inward of the stent body, and a second diminished connection portion holder 13 having 40 to 60% of the number of connection portions between a plurality of annular bodies 2 located between the two first diminished connection portion holders.

[0039] Further, the connecting portions 31 and 32 include a first-pattern connecting portion 31 that extends obliquely at a predetermined angle with respect to the central axis of the stent body, and a second-pattern connecting portion 32 that extends obliquely at a predetermined angle with respect to the central axis of the stent body and in a direction different from that of the first-pattern connecting portion 3l. And the connecting portions between the opposing annular bodies 2 are either the first-pattern connecting portion 31 or the second-pattern connecting portion 32, and are the same-pattern connecting portions. The connecting portions adjacent to each other in the axial direction of the stent body are arranged such that the first-pattern connecting portion 31 and the second-pattern connecting portion 32 alternate with each other.

[0040] In particular, in the in-vivo implantable stent 1 of this embodiment, as shown in FIGS. 1 and 2, the connecting portion group 15a located at one end portion (between one annular body and the annular body adjacent thereto) is entirely composed of the first-pattern connecting portions 31 that extend obliquely downward to the left (in the drawing) at a predetermined angle with respect to the central axis of the stent body. And the connecting portion group 16a adjacent to the connecting portion group 15a in the axial direction of the stent body 10 is entirely composed of the second-pattern connecting portions 32 that extend obliquely downward to the right (in the drawing) at a predetermined angle with respect to the central axis of the stent body.

[0041] And the connecting portion group 17a adjacent to the connecting portion group 16a in the axial direction of the stent body 10 is entirely composed of the first-pattern connecting portions 31 that extend obliquely downward to the left (in the drawing) at a predetermined angle with respect to the central axis of the stent body. Similarly, the connecting portion group 17b adjacent to the connecting portion group 17a in the axial direction of the stent body 10 is entirely composed of the second-pattern connecting portions 32 that extend obliquely downward to the right (in the drawing) at a predetermined angle with respect to the central axis of the stent body. Thereafter as well, the connecting portion group 17a composed of the first-pattern connecting portions 31 and the connecting portion group 17b composed of the second-pattern connecting portions 32 are arranged to alternate with each other in the axial direction.

[0042] Furthermore, as shown in FIGS. 1 and 2, between the connection portion group 17a and the connection portion group 17b, the connection portion 31 and the connection portion 32 are not continuous in the axial direction of the stent body 10. Specifically, in the direction of the other end of the axis of the connection portion 31 of the connection portion group 17a, in other words, downward (in the drawing), the connection portion 32 of the connection portion group 17b is not located, and below the connection portion 31 (in the drawing), there exists the other end side bending portion 22 that serves as a free end. Similarly, in the direction of the other end of the axis of the connection portion 32 of the connection portion group 17b, in other words, downward (in the drawing), the connection portion 31 of the connection portion group 17a is not located, and below the connection portion 32 (in the drawing), there exists the other end side bending portion 22 that serves as a free end.

[0043] And the connection portion group 15b located at the other end portion (between the annular body at the other end and the adjacent annular body) is composed of all second pattern connection portions 32 that extend obliquely downward to the lower right (in the drawing) at a predetermined angle with respect to the central axis of the stent body. And the connection portion group 16b adjacent to the connection portion group 15b in the axial direction of the stent body 10 is composed of all first pattern connection portions 31 that extend obliquely downward to the lower left (in the drawing) at a predetermined angle with respect to the central axis of the stent body.

[0044] Also, in the in-vivo indwelling stent 1 of this embodiment, the stent body 10 includes two maximum connection portion holding portions 11a and 11b that have connection portions at all positions between the adjacent vertices of the adjacent annular bodies 2 at both ends of the stent body, and between the annular bodies 2 having the maximum connection portion holding portions 11a and 11b and the annular bodies 2 located inside the stent body in the axial direction, there are two first reduced connection portion holding portions 12a and12b that have a number of connection portions equal to 40 - 60% of the number of connection portions in the maximum connection portion holding portion. Between the plurality of annular bodies 2 located between the two first reduced connection portion holding portions 12a and 12b, there are second reduced connection portion holding portions 13a and 13b that have a number of connection portions equal to 40 - 60% of the number of connection portions in the first reduced connection portion holding portion. Note that it is preferable that the first reduced connection portion holding portion has a number of connection portions equal to 45 - 55% of the number of connection portions in the maximum connection portion holding portion. Also, it is preferable that the second reduced connection portion holding portion has a number of connection portions equal to 45 - 55% of the number of connection portions in the first reduced connection portion holding portion.

[0045] Specifically, as shown in Figures 1 and 2, one end (between the annular body at one end and the adjacent annular body) has a maximum connection portion 11a that connects all of the diagonally opposing bent portions 22 on the other end and the bent portion 21 on the one end. Therefore, the annular bodies 2 at one end do not have any bent portions 21 and 22 that become free ends. Furthermore, all the connection portions between the annular body at one end and the adjacent annular body, in other words, the connection portions in the maximum connection portion 11a, are first pattern connection portions 31 that extend diagonally downward to the left (in the drawing) at a predetermined angle with respect to the central axis of the stent body.

[0046] Furthermore, the stent body 10 has a maximum connection portion 11b at the other end (between the annular body at the other end and the adjacent annular body) that connects all of the diagonally opposing bent portions 22 on the other end side and the bent portion 21 on the one end side. For this reason, there are no free-end bent portions 21 and 22 between the annular bodies 2 at the other end. The connection portions between the annular body at the other end and the adjacent annular body, in other words, the connection portions in the maximum connection portion 11b, are all second pattern connection portions 32 that extend diagonally downward to the right at a predetermined angle with respect to the central axis of the stent body (in the drawing).

[0047] Furthermore, the space between the annular body 2 having the most connection portion 11a at one end and the annular body 2 located axially inward from the stent body is a first reduced number of connection portion 12a, which has 40 to 60% of the number of connection portions in the most connection portion 11a. In the examples shown in Figures 1 and 2, the number of connection portions in the most connection portion 11a is 16, and the number of connection portions in the first reduced number of connection portion 12a is 8, which is 50% of the number of connection portions in the most connection portion 11a. The connection portions in the first reduced number of connection portion 12a are arranged at equiangled angles with respect to the central axis of the stent body 10.

[0048] Similarly, the space between the annular body 2 having the most connection portion 11b at the other end and the annular body 2 located axially inward from the stent body is a first reduced number of connection portion 12b, which has 40-60% of the number of connection portions in the most connection portion 11b. In Figures 1 and 2, the number of connection portions in the most connection portion 11b is 16, and the number of connection portions in the first reduced number of connection portion 12b is 8, which is 50% of the number of connection portions in the most connection portion 11b. The connection portions in the first reduced number of connection portion 12b are arranged at equiangled angles with respect to the central axis of the stent body 10.

[0049] Furthermore, the space between the annular bodies 2 located between the first diminishing connection holders 12a and 12b is a second diminishing connection holder 13a and 13b, each having 40 to 60% of the number of connection parts in the first diminishing connection holder. In Figures 1 and 2, the number of connection parts in the first diminishing connection holders 12a and 12b is 8, and the number of connection parts in the second diminishing connection holders 13a and 13b is 4, which is 50% of the number of connection parts in the first diminishing connection holders 12a and 12b. The connection parts in the second diminishing connection holders 13a and 13b are arranged at equal angles with respect to the central axis of the stent body 10.

[0050] Furthermore, the in vivo stent of the present invention may also be an in vivo stent 1b having an unfolded view during self-expansion as shown in Figure 5. The main differences between the in vivo stent 1b and the in vivo stent 1 described above are the number of bent portions 21 at one end and bent portions 22 at the other end of the annular body 2b of the stent body 10b, and the number of vertices at one end and the other end of the annular body 2b.

[0051] In the in vivo stent 1b, the number of bent portions 21 at one end and 22 at the other end of the annular body 2b, and the number of vertices at one end and the other end of the annular body 2b are each 12. Furthermore, as shown in Figure 5, in the in vivo stent 1b, the number of connections in the most numerous connection portion holding portions 11a and 11b is 12, and the number of connections in the first reduced connection portion holding portions 12a and 12b is 6, which is 50% of the number of connections in the most numerous connection portion holding portion 11a. Also, the number of connections in the first reduced connection portion holding portions 12a and 12b is 6, and the number of connections in the second reduced connection portion holding portions 13a and 13b is 3, which is 50% of the number of connections in the first reduced connection portion holding portions 12a and 12b.

[0052] Furthermore, the in vivo stent of the present invention may also be an in vivo stent 1c having an unfolded view during self-expansion as shown in Figure 6. The main difference between the in vivo stent 1c and the in vivo stent 1 described above is the number of annular bodies 2 in the stent body 10c and the resulting total length of the stent body 10c. In the in vivo stent 1c, the number of annular bodies 2 is 21. The axial length of each annular body and connection part, and the diameter of each annular body are the same as those of the in vivo stent 1.

[0053] Furthermore, in the in vivo stent 1c of this embodiment, one maximum connection holder portion 11a, 11b and one first reduction connection holder portion 12a, 12b are provided at both ends of the stent body 10c. Between the two first reduction connection holder portions 12a, 12b, there are many second reduction connection holder portions 13a, 13b. Therefore, the number of second reduction connection holder portions 13a, 13b differs significantly between the in vivo stent 1c and the in vivo stent 1 described above.

[0054] Figures 11 and 12 are a front view and a side view of the main components of the coating apparatus. The coating apparatus 200 includes a chamber 210, a holder 220, a moving device 230, a first coating head 240, a second coating head 245, a first position information acquisition device 270, a second position information acquisition device 280, and a control unit 290.

[0055] The chamber 210 comprises a base 212, a main frame 214 positioned on the base 212, and a duct 216 connected to the top. The main frame 214 is covered from the outside with a transparent synthetic resin plate, making the inside of the chamber 210 airtight. An air conditioning unit 218 is connected to the duct 216. The air conditioning unit 218 supplies air with adjusted temperature and humidity to the chamber 210. Therefore, it is possible to maintain a constant temperature and humidity inside the chamber 210 and keep the coating conditions constant. Reference numeral 215 indicates a support frame horizontally mounted on the main frame 214.

[0056] The retainer 220 is positioned at the bottom inside the chamber 210 and is used to hold the stent body 10. It has a base 222, a chuck 224, a motor 226, and a mandrel 228.

[0057] The base portion 222 is mounted on the moving device 230 and, as will be described later, is movable in the X-Y direction, and a chuck portion 224 and a motor 226 are arranged thereon. The chuck portion 224 is used to chucking the base end of the mandrel 228. The motor 226 is configured to allow the chuck portion 224 to rotate in forward and reverse directions. The mandrel 228 has an outer circumference on which the stent body 10 is detachably mounted. Therefore, the holder 220 can rotate the stent body 10 mounted on the mandrel 228 in forward and reverse directions, move it in the X direction, and move it in the Y direction.

[0058] The moving device (corresponding to the means of movement) 230 is used to move the holder 220 in the X-Y direction and has an X-direction moving mechanism 231 and a Y-direction moving mechanism 236. The X-direction moving mechanism 231 has a running rail 233 that extends in the X direction and has a linear motor drive source, and an X-direction moving table 234 that moves along the running rail 233. The Y-direction moving mechanism 236 has a running rail 237 that extends in the Y direction, a Y-direction moving table 238 that moves along the running rail 237, and a motor 239 that drives the Y-direction moving table 238. The running rail 237 is placed on the X-direction moving table 234, and the base 222 of the holder 220 is placed on the Y-direction moving table 238.

[0059] As shown in Figures 12 and 11, the first coating head 240 and the second coating head 245 are located in the middle of the chamber 210 and are used to apply the coating liquid, and have a dispenser 252, a vertical table 253, a bracket 258, and a nozzle section 262.

[0060] The dispenser 252 has a cylinder section 255, a piston section 256, and a drive section 257, and is mounted on a vertical table 253. The vertical table 253 is mounted on a support frame 215 of the chamber 210 via a bracket 258, and is configured to allow the dispenser 252 to move in the Z direction by a screw feed mechanism driven by a motor 254.

[0061] The cylinder portion 255 is a container for storing the coating liquid and is attached to the vertical table 253. The piston portion 256 is slidably positioned within the cylinder portion 255. The drive unit 257 has, for example, a motor or a hydraulic mechanism and is configured to press the piston portion 256 with a predetermined force.

[0062] The nozzle portion 262 communicates with the cylinder portion 255 and includes a mounting member 264 and a nozzle 266. The mounting member 264 is positioned at the lower end of the cylinder portion 255 and is used to connect the nozzle 266 to the cylinder portion 255.

[0063] The second coating head 245 shown in Figure 11 is located in the middle of the chamber 210 and is used to apply the coating liquid. The second coating head 245 is substantially the same as the first coating head 240, except that a different coating liquid is stored in the cylinder portion 255, so its description is omitted.

[0064] The first position information acquisition device 270 is an imaging means provided for acquiring position information in the X-Y direction in a Cartesian coordinate system on the surface of the stent body 10 (strut), and is attached to the support frame 215 via a bracket 272. The first position information acquisition device 270 has a camera unit 274 and a line sensor unit arranged to extend in the axial direction of the stent body 10. The line sensor unit is used to scan the surface of the stent body 10 in synchronization with the rotation of the stent body 10 attached to the mandrel 228 of the holder 220, acquire image data of the surface of the stent body 10, and transmit it to the control unit 290.

[0065] The second position information acquisition device 280 is a Z-direction displacement measuring means provided to acquire position information in the Z-direction in a Cartesian coordinate system on the surface of the stent body 10 (strut). It is fixed to the lower end of a bracket 282 attached to the support frame 215 and has a laser displacement sensor 284. The laser displacement sensor 284 is a vertical sensor that measures the Z-direction displacement of the linear first strut portion 23 and the linear second strut portion 24. It is used to scan along a trajectory passing through the centers of the linear first strut portion 23, the linear second strut portion 24 and the bent portions 21 and 22 while rotating the stent body 10 in forward and reverse directions, acquire Z-direction displacement data for the entire stent body 10, and transmit it to the control unit 290. The measurement start point is not particularly limited, but for example, it may coincide with the application start position.

[0066] The control unit 290 is located outside the chamber 210 and includes, for example, a microprocessor that controls the above-mentioned parts and performs various calculations according to a program, a memory for storing various settings and data, a monitor for displaying various settings and data, a keyboard for inputting various settings and data, etc., and is used to control the holder 220, the moving device 230, the first coating head 240, the second coating head 245, the first position information acquisition device 270, and the second position information acquisition device 280.

[0067] The calculation processes include, for example, a process for acquiring position information in the X-Y direction, a process for acquiring position information in the Z direction, and a process for setting the coating path by the nozzle 266.

[0068] In the process for acquiring position information in the X-Y direction, based on the fact that the brightness of the stent body 10 (strut) is high and the brightness of the void is low, the image data of the surface of the stent body 10 acquired from the first position information acquisition device 270 is binarized with an appropriate brightness to separate the stent body 10 (strut) from the void, and converted into the X-Y coordinates of the stent body 10 (strut), that is, position information in the X-Y direction in a Cartesian coordinate system, and stored in memory. The obtained position information in the X-Y direction is used to calculate the coordinates of the trajectory passing through the center of the stent body 10 (strut), and the obtained trajectory coordinates are stored in memory.

[0069] In the process for acquiring position information in the Z direction, the Z-direction displacement data of the entire stent body 10 acquired from the second position information acquisition device 280 is converted into Z-direction position information in the Cartesian coordinate system of the surface of the stent body 10 (strut) and stored in memory. The stent body 10 (strut) is not strictly a smooth surface, but has irregularities. Therefore, in order to apply each coating liquid quantitatively and precisely, it is necessary to control the movement of the tip of the nozzle 266 based on the Z-direction position information so that it is strictly parallel to the surface of the stent body 10 (strut), and to apply a predetermined amount of each coating liquid.

[0070] In the process of setting the coating path for each coating liquid by the nozzle 266, the position information in the X-Y direction and the Z direction of the stent body 10 (linear strut sections 23, 24, bent sections 21, 22, and connecting sections 31, 32) in the Cartesian coordinate system is used to calculate the settings for continuous coating on the stent body 10 (struts).

[0071] Next, the stent delivery system 50 of the present invention will be described with reference to Figures 7 to 10. The stent delivery system 50 of the present invention comprises a sheath 52, a stent 1 for implantation in a living body housed in the tip of the sheath 52, and an inner tube 54 that is slidably inserted inside the sheath 52 and pushes the stent 1 for implantation in a living body out from the tip of the sheath 52.

[0072] The in vivo stent 1 is as described above. The stent delivery system 50 of this embodiment comprises a sheath 52, a self-expanding in vivo stent 1, and an inner tube 54, as shown in Figure 7.

[0073] As shown in Figures 7, 8, and 10, the sheath 52 is tubular and has openings at its tip and rear end. The tip opening functions as a discharge port for the in vivo stent 1 when it is placed in a narrowed area within a body cavity. The in vivo stent 1 is pushed out through this tip opening, releasing the stress load and expanding to return to its pre-compression shape. The tip of the sheath 52 is a stent housing section 55 that houses the in vivo stent 1 inside. The sheath 52 also has a side hole 41 provided on the proximal end side of the stent housing section 55. The side hole 41 is for guiding the guide wire to the outside.

[0074] Furthermore, as shown in Figures 7 and 9, a sheath hub 56 is fixed to the base end of the sheath 52. As shown in Figure 9, the sheath hub 56 comprises a sheath hub body 61 and a valve body 62 housed within the sheath hub body 61, which slidably and liquid-tightly holds the inner tube 54. The sheath hub 56 also includes a side port 63 that branches diagonally rearward from near the center of the sheath hub body 61.

[0075] Furthermore, the sheath hub 56 is equipped with an inner tube locking mechanism that restricts the movement of the inner tube 54. In this embodiment, the locking mechanism consists of a valve body 62 that clamps the base end of the inner tube 54 in a liquid-tight manner by compression, an operating member 64 that compresses the valve body 62, and the sheath hub body 61. By providing this locking mechanism, the inner tube 54 can be fixed in any position relative to the sheath 52. The valve body 62 is installed in a valve body housing recess provided at the base end of the sheath hub body 61, and an inner tube insertion passage that forms part of the inner tube lumen is formed inside the valve body 62. In addition, the inner diameter of the valve body housing recess is made slightly larger than the outer diameter of the valve body 62, allowing the valve body 62 to expand radially when compressed by the operating member 64. The internal shape of the valve body 62 (in other words, the shape of the inner tube insertion passage) is made into a shape in which two substantially spherical shapes partially overlap in the axial direction, with both ends and the center part having a reduced diameter.

[0076] The operating member 64 has a cylindrical valve body pressing portion 64a protruding towards the tip in the central part, an inner cylindrical portion 64c formed to enclose the valve body pressing portion 64a and having a screw portion 64b that can be screwed into a screw portion 61a formed on the outer surface of the rear end of the sheath hub body 61, and a cylindrical gripping portion 64d formed to enclose the inner cylindrical portion 64c. The gripping portion 64d is the part used to grip the operating member 64 when it is rotated. Furthermore, an internal passage is formed inside the valve body pressing portion 64a, specifically inside the valve body pressing portion 64a, forming part of the lumen for the inner tube. Also, as shown in Figure 9, the tip portion of the valve body pressing portion 64a is inserted into the recess for housing the valve body, and the valve body 62 can be compressed by moving the operating member to the tip.

[0077] In this embodiment of the locking mechanism, when the operating member 64 is rotated to advance the screwing process so that it moves toward the tip of the sheath hub 56, the tip of the valve body pressing portion 64a comes into contact with the rear end of the valve body 62. Further rotation of the operating member 64 to advance the screwing process compresses the valve body 62 in the axial direction. As the compression of the valve body 62 progresses, the inner diameter of the internal passage decreases, and finally the inner tube 54 is gripped and fixed by the valve body 62. The locking mechanism is released by the reverse rotation operation described above.

[0078] Furthermore, a reinforcing tube 66 is provided between the base end of the sheath 52 and the sheath hub 56, extending from the tip of the sheath hub 56 toward the tip. This reinforcing tube 66 prevents kinking of the sheath 52 at the tip of the sheath hub 56. It is preferable to use a heat-shrinkable tube as the reinforcing tube.

[0079] As shown in Figures 7, 8, and 9, the inner tube 54 comprises a shaft-shaped inner tube body portion 40, a tip portion 47 provided at the tip of the inner tube body portion 40 and protruding from the tip of the sheath 52, and an inner tube hub 70 fixed to the base end of the inner tube body portion 40.

[0080] The tip portion 47 preferably protrudes from the tip of the sheath 52 and is tapered, gradually decreasing in diameter towards the tip, as shown in Figure 8. This configuration facilitates insertion into the stenosis. Furthermore, the inner tube 54 is preferably located on the tip side of the in-vivo stent 1 and is equipped with a stopper to prevent the sheath from moving toward the tip. The base end of the tip portion 47 is capable of contacting the tip of the sheath 52 and functions as the stopper described above.

[0081] Furthermore, as shown in Figure 8, the inner tube 54 is provided with two protrusions 43 and 45 for holding the in vivo stent 1. The protrusions 43 and 45 are preferably annular. A stent-holding protrusion 43 is provided on the proximal end side of the tip 47 of the inner tube 54. The in vivo stent 1 is positioned between the two protrusions 43 and 45. Therefore, the area between these two protrusions 43 and 45 in the stent delivery system 50 is the stent storage area 55. In other words, the inner tube 54 is provided with a stent extrusion protrusion 45 located on the proximal end side of the stent storage area 55, and a stent-holding protrusion 43 located on the tip side of the stent storage area 55. The outer diameters of these protrusions 43 and 45 are sized to be in contact with the compressed in vivo stent 1, which will be described later.

[0082] Therefore, the in vivo stent 1 is restricted from moving toward the tip by the protruding portion 43 and from moving toward the proximal end by the protruding portion 45. Then, as shown in Figure 10, when the sheath 52 moves backward, the in vivo stent 1 is exposed by the sheath 52, expands, and is eventually discharged as a whole.

[0083] As shown in Figure 8, the inner tube 54 includes a lumen 48 that extends from its tip to at least the proximal end side of the stent housing portion 55 of the sheath 52, and an inner tube side hole 42 that communicates with the lumen 48 on the proximal end side of the stent housing portion. In this embodiment of the stent delivery system 50, the lumen 48 terminates at the location where the inner tube side hole 42 is formed. The lumen 48 is for inserting one end of a guide wire from the tip of the stent delivery system 50, partially inserting it into the inner tube, and then leading it out to the outside from the side of the inner tube. The inner tube side hole 42 is located slightly towards the tip of the stent delivery system 50 from the sheath side hole 41.

[0084] The inner tube 54 penetrates the sheath 52 and protrudes from the rear end opening of the sheath 52. An inner tube hub 70 is fixed to the base end of the inner tube 54, as shown in Figures 7 and 10.

[0085] Furthermore, in the stent delivery system of this embodiment, a rigid pipe 72 is fitted over the base end of the inner tube 54. This rigid pipe 72 extends a predetermined distance toward the tip from the base end of the inner tube 54, and at least the tip of the pipe 72 penetrates into the sheath hub 56 and extends to a position that is toward the tip of the valve body 62. Furthermore, it is preferable that the base end of the inner tube 54 is provided with an insertion depth restricting portion that restricts the distance the sheath 52 moves toward the tip. The inner tube 54 is provided with an insertion depth restricting tube 73 at its base end. The outer diameter of this tube 73 is larger than the inner diameter of the passage of the operating member 64 of the sheath hub 56, and it is impossible for it to penetrate into the sheath hub 56.

[0086] Next, the method of using the stent delivery system 50 of the present invention will be explained with reference to the drawings. First, as shown in Figure 10, the rear end 9a of the guide wire 9 is inserted from the tip of the lumen 48 of the inner tube 54, and is led out to the outside by passing it through the side hole 42 of the inner tube 54 and the side hole 41 of the sheath 52. Then, the sheath 52 is grasped and the stent delivery system 50 of the present invention is inserted into a body cavity (for example, a blood vessel) along the guide wire 9 to position the target in vivo stent 1 for placement in the stenotic area.

[0087] Next, the sheath 52 is moved axially towards the proximal end. At this time, the rear end face of the in vivo stent 1 abuts against the tip surface of the stent extrusion projection 45 and is locked in place, so it is released from the tip opening of the sheath 52 as the sheath 52 moves. As a result of this release, the in vivo stent 1 expands itself, as shown in Figure 10, and expands the stenotic area, and is then placed within the stenotic area. After that, the inner tube 54 is moved axially towards the proximal end and stored inside the sheath 52, and the procedure is completed by removing the sheath 52 together with the inner tube 54 from the body cavity.

[0088] The self-expanding in vivo stent of the present invention comprises a tubular stent body and a drug-containing coating provided on the outer surface of the stent body, and is an in vivo stent that can be reduced in diameter by compression in the central axis direction and restored to its pre-reduced shape by releasing the compression. The stent body comprises an annular body formed of a wavy linear component having a plurality of bent portions having vertices on one end and the other end in the axial direction, and a connecting portion that connects the annular bodies when the plurality of annular bodies are arranged in the axial direction of the stent body. Between adjacent annular bodies in the axial direction of the in vivo stent, the vertices of the adjacent bent portions are offset in the circumferential direction of the stent body, and between adjacent annular bodies in the axial direction of the in vivo stent, except for the annular bodies located at both ends of the stent body, they are not connected by the connecting portion and are free ends, and have bent portions that are close to each other and facing each other diagonally in the axial direction. Furthermore, when the in vivo implantable stent is uncompressed, the distance (D1) between the vertices of adjacent bent portions that are free ends is 0.485 mm or less, and the circumferential distance Y of the stent body between the vertices of the bent portions satisfies the following equation (I) in relation to the axial distance X: Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, a drug-containing coating is provided on the outer surface of the free end and adjacent bent portion. When the in vivo implantable stent is uncompressed, the free end and adjacent bent portion satisfy the above-mentioned conditions, and when the drug-containing coating is formed on the outer surface of the stent body when uncompressed, the formation of a thin drug film between the adjacent free end bent portions can be suppressed. In addition, since the distance between the vertices of the free end and adjacent bent portion (D1) is 0.485 mm or less, the implantation site of the stent where the free end and adjacent bent portion are located can be well expanded and maintained when uncompressed.

[0089] Embodiments of the in vivo stent of the present invention are as follows: (1) An in vivo stent comprising a tubular stent body and a drug-containing covering portion provided on the outer surface of the stent body, wherein the diameter can be reduced by compression in the central axis direction and restored to the shape before the reduction by releasing the compression, wherein the stent body comprises an annular body formed of a wavy linear component having a plurality of bent portions having vertices on one end and the other end in the axial direction, and a connecting portion that connects the annular bodies when the plurality of annular bodies are arranged in the axial direction of the stent body, wherein between adjacent annular bodies in the axial direction of the in vivo stent, the vertices of the adjacent bent portions are offset in the circumferential direction of the stent body, and between adjacent annular bodies in the axial direction of the in vivo stent, except for the annular bodies located at both ends of the stent body, they are not connected by the connecting portion and are free ends, and have bent portions that are close to each other and facing each other diagonally in the axial direction, Furthermore, when the in vivo implantable stent is uncompressed, the distance (D1) between the vertices of the free ends and adjacent bent portions is 0.485 mm or less, and the distance between the vertices of the bent portions satisfies the following equation (I) in relation to the axial distance X, where Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, the drug-containing coating is provided on the outer surface of the free end and adjacent to the bent portion of the in vivo stent.

[0090] This self-expanding in vivo stent comprises a tubular stent body and a drug-containing coating provided on the outer surface of the stent body. It is an in vivo stent that can be reduced in diameter by compression in the central axis direction and restored to its original shape by releasing the compression. The stent body comprises an annular body formed from a wavy linear component having multiple bent portions with vertices at one end and the other end in the axial direction, and connecting portions that connect the annular bodies when the multiple annular bodies are arranged in the axial direction of the stent body. Between adjacent annular bodies in the axial direction of the in vivo stent, the vertices of the adjacent bent portions are offset in the circumferential direction of the stent body. Furthermore, between adjacent annular bodies in the axial direction of the in vivo stent, except for those located at both ends of the stent body, they are not connected by connecting portions, are free ends, and have bent portions that are close to each other and facing each other diagonally in the axial direction. Furthermore, when the in vivo implantable stent is uncompressed, the distance (D1) between the vertices of adjacent bent portions that are free ends is 0.485 mm or less, and the circumferential distance Y of the stent body between the vertices of the bent portions satisfies the following equation (I) in relation to the axial distance X: Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, a drug-containing coating is provided on the outer surface of the free end and adjacent bent portion. When the in vivo implantable stent is uncompressed, the free end and adjacent bent portion satisfy the above-mentioned conditions, and when the drug-containing coating is formed on the outer surface of the stent body when uncompressed, the formation of a thin drug film between the adjacent free end bent portions can be suppressed. In addition, since the distance between the vertices of the free end and adjacent bent portion (D1) is 0.485 mm or less, the implantation site of the stent where the free end and adjacent bent portion are located can be sufficiently expanded and held when uncompressed.

[0091] Furthermore, the following embodiments of the above-mentioned in vivo stent may also be: (2) The in vivo stent according to (1) above, wherein the distance (shortest distance, D2) between the free ends and adjacent bent portions is 0.2 mm or less. (3) The in vivo stent according to (1) or (2) above, wherein the distance (D1) between the vertices of the free ends and adjacent bent portions is 0.10 to 0.24 mm. (4) The in vivo stent according to any one of (1) to (3) above, wherein the length of the connection portion is 0.40 to 0.45 mm. (5) The in vivo stent according to any one of (1) to (4) above, wherein the axial length of the annular body is 1.3 to 1.7 mm. (6) The in vivo stent is the in vivo stent according to any one of (1) to (5) above, wherein the angle of inclination of the stent body with respect to the axial direction of the connection portion in the unfolded view of the in vivo stent when it is uncompressed is 110 to 130 degrees. (7) The in vivo stent is the in vivo stent according to any one of (1) to (6) above, wherein the ratio of the outer surface area occupied by the outer surface of the stent body to the outer peripheral area of ​​the virtual cylinder when the in vivo stent is uncompressed is 15% to 20%. (8) The in vivo stent is the in vivo stent according to any one of (1) to (7) above, wherein the expansion force is 9 to 11 N / cm. (9) The in vivo stent is the in vivo stent according to any one of (1) to (8) above, wherein the drug-containing coating portion contains sirolimus or a sirolimus derivative as a drug.

[0092] Furthermore, embodiments of the stent delivery system of the present invention are as follows: (10) A stent delivery system comprising a sheath, a stent for implantation in a living body as described in any of (1) to (9) above, housed in the tip of the sheath, and an inner tube that is slidably inserted through the sheath and for pushing the stent for implantation in a living body out from the tip of the sheath.

Claims

1. An in vivo stent comprising a tubular stent body and a drug-containing coating portion provided on the outer surface of the stent body, wherein the diameter can be reduced by compression in the central axis direction and restored to its pre-reduced shape by releasing the compression, wherein the stent body comprises an annular body formed of a wavy linear component having a plurality of bent portions having vertices on one end and the other end in the axial direction, and a connecting portion connecting the annular bodies when the plurality of annular bodies are arranged in the axial direction of the stent body, wherein between adjacent annular bodies in the axial direction of the in vivo stent, the vertices of the adjacent bent portions are offset in the circumferential direction of the stent body, and between adjacent annular bodies in the axial direction of the in vivo stent, except for those between annular bodies located at both ends of the stent body, they are not connected by the connecting portion and are free ends, and have bent portions that are close to each other and facing each other diagonally in the axial direction. Furthermore, when the in vivo implantable stent is uncompressed, the distance (D1) between the vertices of the free ends and adjacent bent portions is 0.485 mm or less, and the distance between the vertices of the bent portions satisfies the following equation (I) in relation to the axial distance X, where Y ≥ -0.0028X ２ -0.2927X + 358.87 (I) Furthermore, the drug-containing coating is provided on the outer surface of the free end and adjacent to the bent portion, making it a stent for implantation in a living body.

2. The in vivo stent according to claim 1, wherein the distance (shortest distance, D2) between the free ends and adjacent bent portions is 0.2 mm or less.

3. The in vivo stent according to claim 1 or 2, wherein the distance (D1) between the vertices of the adjacent free ends of the bent portions is 0.10 to 0.24 mm.

4. The in vivo stent according to claim 1 or 2, wherein the length of the connecting portion is 0.40 to 0.45 mm.

5. The in vivo stent according to claim 1 or 2, wherein the axial length of the annular body is 1.3 to 1.7 mm.

6. The in vivo stent according to claim 1 or 2, wherein the inclination angle of the stent body of the connection portion with respect to the axial direction in the uncompressed unfolded view of the in vivo stent is 110 to 130 degrees.

7. The in vivo stent according to claim 1 or 2, wherein the ratio of the outer surface area of ​​the stent body to the outer surface area of ​​the virtual cylindrical body when the in vivo stent is uncompressed is 15% to 20%.

8. The in vivo stent according to claim 1 or 2, wherein the in vivo stent has an expansion force of 9 to 11 N / cm.

9. The in vivo stent according to claim 1 or 2, wherein the drug-containing coating portion contains sirolimus or a sirolimus derivative as the drug.

10. A stent delivery system comprising a sheath, a stent for in-vivo implantation according to claim 1 or 2 housed within the tip of the sheath, and an inner tube slidably inserted through the sheath for pushing the stent for in-vivo implantation out from the tip of the sheath.

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