JP2010233744A - In vivo indwelling stent and biological organ dilator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an in vivo indwelling stent composed of a stent body and a resin layer containing a physiological active agent and covering the outer surface of the stent body in which peeling of the resin layer containing a physiological active agent is prevented at outer edges of bent parts of the stent body that deform when the stent is dilated. <P>SOLUTION: The stent 1 is formed from a linear body having a predetermined line width. The stent is provided with the stent body 2 including annular bodies 5 each having a plurality of one-end side bent parts 21 having apexes on one end side in the axial direction of the stent and a plurality of the other-end bent parts 22 having apexes on the other end side and connecting parts 13 connecting the adjacent annular bodies 5 and the resin layer 3 containing a physiological active agent and covering the outer surface of the stent body 2. Each of the bent parts, namely, each of the one-end side bent parts 21 or the other-end side bent parts 22 is formed by making a defect on a part of the inner surface side of the bent part and has a thin part 14 that extends from an inner edge on the inner surface side to the direction of an outer edge. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an in-vivo indwelling stent and a biological organ dilator used to improve a stenosis or occlusion in a biological lumen such as a blood vessel, a bile duct, a trachea, an esophagus, or a urethra.

In-vivo stents are used to expand the stenosis or occlusion site and secure the lumen to treat various diseases caused by stenosis or occlusion of blood vessels or other in-vivo lumens. In general, it is a tubular medical device.
Since the stent is inserted into the body from outside the body, the diameter is small at that time. The stent is expanded at the target stenosis or occlusion site to increase the diameter, and the lumen is held as it is.

As the stent, a metal wire or a cylindrical shape obtained by processing a metal tube is generally used. It is attached to a catheter or the like in a thin state, inserted into a living body, expanded by a certain method at a target site, and tightly fixed to the inner wall of the lumen to maintain the lumen shape. Stents are classified into self-expandable stents and balloon expandable stents according to function and placement method. The balloon expandable stent has no expansion function in the stent itself. After inserting the stent into the target site, the balloon is positioned in the stent to expand the balloon, and the stent is expanded (plastic deformation) by the expansion force of the balloon. Fix it in close contact with the inner surface of the lumen. This type of stent requires the above-described stent expansion operation.
The balloon expandable stent is expanded by plastically deforming the stent with an expanding balloon, and is in close contact with the inner surface of a target lumen (for example, a blood vessel). The balloon expandable stent has a high expansion maintenance force (radial force) due to plastic deformation.

The purpose of stent placement is to prevent and reduce restenosis that occurs after a procedure such as PTCA. And in recent years, a bioactive substance is carried on the stent so that the bioactive substance can be locally released over a long period of time at the indwelling site of the lumen to reduce the restenosis rate. .
Recently, a bioactive substance such as an anticancer agent is supported on the stent, and this bioactive substance is locally released at the site where the stent is placed in the lumen to reduce the restenosis rate. Many attempts have been made. For example, as in JP-T-2004-533409 (Patent Document 1), local sustained release of a physiologically active substance is realized by carrying a coating layer in which an anticancer agent is contained in a polyolefin-based elastomer on a stent. Moreover, in Japanese translations of PCT publication No. 2004-518458 (patent document 2), the sustained release of an immunosuppressive agent is achieved using an acrylate-type polymer as a medicine carrying polymer. These bioactive substance-supported polymers are stable in the living body and have a characteristic of being resistant to deterioration such as cracking even after being placed in a blood vessel. However, since they are non-biodegradable polymers, the polymers after bioactive substances disappear Continues to remain in the blood vessels. Since these polymers are not less inflammatory, there is a concern of causing restenosis and thrombotic complications in the late period.

In addition, many studies using biodegradable polymers as supporting polymers for physiologically active substances have been found. For example, as disclosed in JP-A-8-33718 (Patent Document 3), a drug such as dexamethasone and a biodegradable polymer such as polylactic acid are dissolved in a solvent, and then the solution is sprayed onto the stent. The company manufactures stents that can release drugs by evaporation. The biodegradable polymer is decomposed and absorbed by the living body and disappears at the same time as the bioactive substance is released or after the bioactive substance is released. Low risk of restenosis and thrombotic complications in late period. Among biodegradable polymers, aliphatic polyesters such as polylactic acid have high biocompatibility, and are therefore widely studied as a support polymer for physiologically active substances.
Then, as shown in Japanese Patent Application Laid-Open No. 2007-97706 (Patent Document 4), the applicant of the present application includes a composition containing a physiologically active substance, a biodegradable polymer, and a plasticizer on at least a part of the surface of the stent body. A stent that is placed in an in vivo lumen having a layer formed of

Special table 2004-533409 gazette JP-T-2004-518458 JP-A-8-33718 JP 2007-97706 A

In the stent of Patent Document 4, the bioactive substance is gradually released into the living body as the biodegradable polymer is decomposed in the living body, and appropriate treatment can be performed. In addition, since the layer is given flexibility by the plasticizing effect of the plasticizer, it is possible to significantly suppress / prevent the destruction of the layer during the manufacturing process, the transportation process, and the stent expansion during clinical use. Is effective.
However, the present inventor has found that when this stent is applied to a balloon expandable stent, there is a possibility of peeling at the outer edge portion of the bent portion that is deformed when the stent is expanded.
Accordingly, an object of the present invention is to provide a stent substrate having a plurality of bent portions that are formed by a linear body having a predetermined line width and deformed when the stent is expanded, and a bioactive substance-containing resin layer that covers the outer surface of the stent substrate. The stent for living body indwelling in which the peeling of the bioactive substance containing resin layer in the outer edge part of the bending part which deform | transforms at the time of expansion of a stent is very little, and a living organ expansion device using the same are provided.

What achieves the above object is as follows.
(1) A stent for in-vivo indwelling, which is formed into a substantially tubular body, has a diameter for insertion into a lumen in a living body, and expands when a force spreading radially from the inside is applied,
The stent is formed of a linear body having a predetermined line width, and has a plurality of one-end bent portions having apexes on one end side in the axial direction of the stent and a plurality of apexes on the other end side in the axial direction of the stent. A stent base comprising a plurality of annular bodies having a bent portion at the other end, and a connecting portion for connecting the adjacent annular bodies, and a physiologically active substance-containing resin partially covering the entire outer surface or the outer surface of the stent base With layers,
The one-end-side bent portion and the other-end-side bent portion, which are deformed when the stent is expanded, and more than half of the bent portions covered with the physiologically active substance-containing resin layer, A stent for indwelling in vivo, comprising a thin portion formed by partially losing the inner surface side of the bent portion, and the thin portion extending from the inner edge of the bent portion toward the outer edge.

(2) The indwelling stent according to (1), wherein the bending portion of the portion having the thin-walled portion has a neutral surface located on the outer edge side with respect to the center line of the line width of the bending portion. .
(3) The in-vivo indwelling stent according to (1) or (2), wherein the thin-walled portion extends from the inner side of the central portion of the bent portion and from the inner edge toward the outer edge.
(4) The above-described (1) to (1), wherein the thin-walled portion has one end positioned at the inner edge of the bent portion and the other end positioned near the center line of the line width of the bent portion or on the outer edge side from the center line. 3) The stent for in-vivo indwelling in any one of.
(5) The bending portion that is a bending portion that is deformed when the stent is expanded and that is 80% or more of the bending portion that is coated with the physiologically active substance-containing resin layer has the thin portion. (4) The stent for in-vivo indwelling in any one of.
(6) The in-vivo indwelling stent according to any one of (1) to (5), wherein the thin portion is any one of a fan shape, a crescent shape, a circular shape, and a rectangular shape.
(7) The in-vivo indwelling stent according to any one of (1) to (6), wherein a portion of the bent portion where the thin portion is provided has a substantially constant thickness.
(8) The above-described (1) to (6), wherein the portion of the bent portion where the thin portion is provided is thicker continuously or stepwise from the inner edge of the bent portion toward the outer edge. The stent for indwelling in any one of (4).
(9) The stent base has a bent portion that does not substantially deform or has a small amount of deformation when the stent is expanded, and the bent portion that does not substantially deform or has a small amount of deformation when the stent is expanded includes The in-vivo indwelling stent according to any one of (1) to (8), wherein a thin-walled portion is not provided.
(10) The in-vivo stent according to any one of (1) to (9), wherein the bioactive substance-containing resin layer is formed of a biodegradable polymer containing a bioactive substance.
(11) The annular body according to any one of (1) to (10), wherein the annular body is an annular endless member having a linear portion connecting the one end side bent portion and the other end side bent portion. In vivo indwelling stent.

Moreover, what achieves the said objective is as follows.
(12) The above-described (1) mounted so as to enclose the tube-shaped shaft main body, a foldable and expandable balloon provided at the tip of the shaft main body, and the balloon in the folded state. A living organ dilating instrument comprising the stent according to any one of (11) to (11).

The stent of the present invention is formed of a linear body having a predetermined line width, and has a plurality of one-end bent portions having apexes on one end side in the axial direction of the stent and a plurality of apexes on the other end side in the axial direction of the stent. A stent base including a plurality of annular bodies having a bent portion on the other end side, and a connecting portion connecting adjacent annular bodies, and a physiologically active substance-containing resin layer partially covering the entire outer surface or the outer surface of the stent base; A bent portion at one end side and a bent portion at the other end side that are deformed when the stent is expanded, and more than half of the bent portions covered with the bioactive substance-containing resin layer are bent portions. The thin-walled portion is formed by partially missing the inner surface side, and the thin-walled portion extends from the inner edge of the bent portion toward the outer edge.
For this reason, a bent portion having a thin wall portion has a small amount of deformation on the outer edge side when the stent is expanded, and there is also little deformation of the bioactive substance-containing resin layer in the portion covering the outer edge side of the bent portion. Very little.

FIG. 1 is a front view of an in-vivo stent according to an embodiment of the present invention. FIG. 2 is a diagram of the in-vivo indwelling stent of FIG. 1 deployed and viewed from the inner surface side. FIG. 3 is a partially enlarged view of FIG. 4 is a cross-sectional view taken along line AA in FIG. FIG. 5 is an explanatory view for explaining the cross-sectional shape of the bent portion of the in-vivo stent according to another embodiment of the present invention. FIG. 6 is an explanatory diagram for explaining the cross-sectional shape of the bent portion of the in-vivo stent according to another embodiment of the present invention. FIG. 7 is an explanatory view for explaining the form of the thin portion provided in the bent portion of the in-vivo stent according to another embodiment of the present invention. FIG. 8 is an explanatory view for explaining the form of the thin portion provided in the bent portion of the in-vivo stent according to another embodiment of the present invention. FIG. 9 is an explanatory view for explaining the form of the thin portion provided in the bent portion of the in-vivo stent according to another embodiment of the present invention. FIG. 10 is a diagram showing a deployed state of the in-vivo indwelling stent shown in FIG. 1 as viewed from the inner surface side. FIG. 11 is a view of a deployed in-vivo stent according to another embodiment of the present invention as viewed from the inner surface side. FIG. 12 is a partially enlarged view of FIG. FIG. 13 is a partially enlarged view of a developed view when the in-vivo indwelling stent shown in FIG. 11 is expanded. FIG. 14 is a partially omitted front view of the living organ dilator according to the embodiment of the present invention. FIG. 15 is an enlarged partial cross-sectional view of the distal end portion of the living organ dilator shown in FIG. FIG. 16 is an explanatory diagram for explaining the operation of the living organ dilator according to the embodiment of the present invention.

The in-vivo indwelling stent of the present invention will be described using the following preferred embodiments.
The in-vivo stent 1 of the present invention is formed in a substantially tubular body, has a diameter for insertion into a lumen in a living body, and expands when a force spreading in the radial direction from the inside of the stent is applied. Is. The stent 1 is formed of a linear body having a predetermined line width, and includes a plurality of one-end bent portions 21 having apexes on one end side in the axial direction of the stent and a plurality of apexes on the other end side in the axial direction of the stent. A stent base 2 comprising a plurality of annular bodies 5 having the other end side bent portion 22 and a connecting portion 13 connecting adjacent annular bodies 5, and a physiological activity that partially covers the entire outer surface or the outer surface of the stent base 2 A substance-containing resin layer 3.
The bent portion 21 is one end-side bent portion 21 and the other end-side bent portion 22 that are deformed when the stent 1 is expanded, and more than half of the bent portions covered with the bioactive substance-containing resin layer 3. , 22 has a thin portion 14 formed by partially missing the inner surface side of the bent portion, and the thin portion 14 extends from the inner edge of the bent portion in the outer edge direction.
In FIG. 1, the outer edge of the thin portion 14 formed on the inner surface side of the stent 1 does not appear on the surface, but is shown by a solid line for explanation.

The in-vivo stent 1 of the present invention includes a stent base 2 and a physiologically active substance-containing resin layer 3 that partially covers the entire outer surface or the outer surface of the stent base 2.
The stent base 2 in this embodiment is a substantially tubular body, has a diameter for insertion into a living body lumen, and is an expandable stent when a force spreading radially from the inside of the stent is applied. Yes, a so-called balloon expandable stent.
And in this stent base | substrate 2, as shown in FIG. 1 thru | or 3, the cyclic | annular body 5 has several one end side bending parts 21 located in the one end side of a stent, and several other end side bending parts located in the other end side. 22 is a wave-like annular body including a linear portion 12 connecting between the bent portion 21, the one end side bent portion 21, and the other end side bent portion 22. And the linear part 12 is a linear part. And the annular body 5 adjacent to the axial direction is such that the other end side bent portion 22 of the annular body 5 located on one end side of the stent and the one end side bent portion 21 of the annular body 5 located on the other end side are close to each other. It is arranged and connected by the connecting part 13.

The stent 1 is inserted into the living body in the state shown in FIG. 1 and expands when a force spreading in the radial direction from the inside of the stent is applied. In the developed view, the state of FIG. 2 is changed to the state of FIG. At the time of the above deformation, the one end side bent portion 21 and the other end side bent portion 22 are deformed in the opening direction, but the linear portion 12 connecting the one end side bent portion 21 and the other end side bent portion 22 is substantially Does not deform.
As shown in FIG. 1 and FIG. 2 which is a development view thereof, the wavy annular body in the stent base 2 includes a plurality of one end side bent portions 21, other end side bent portions 22 and linear portions 12 having substantially the same pitch. It has an endless wavy body that is annularly continuous. In addition, 4-10 are suitable for the number of the peaks (or valleys) of the wavy annular body. In the stent 1 of this embodiment, a plurality of (specifically, two or three) connecting portions 13 are provided between adjacent annular bodies. In particular, in the stent base 2 of this embodiment, two joint portions are provided between adjacent annular bodies. Although it is preferable to provide a plurality of connecting portions 13 between adjacent annular bodies, only one connecting portion 13 may be provided.
In addition, the form of a stent base | substrate is not limited to what was comprised by several wavy annular bodies like the stent base | substrate 2 mentioned above, and what joins between the adjacent vertices of several wavy annular bodies. Absent.

Then, the one end side bent portion 21 serving as the free end of the stent base 2 or the other end side bent portion 22 serving as the free end, which is deformed when the stent 1 is expanded, is formed from the inner surface side and the inner edge. A thin portion 14 extending in the outer edge direction is provided. In the stent base 2 of this embodiment, since the bent portions 21 and 22 that are all free ends are deformed when the stent 1 is expanded, the thin-walled portion 14 is added to the bent portions 21 and 22 that are all free ends. Is formed. The thin-walled portion 14 is formed on the inner surface side of the bent portion of the stent base 2 and is formed by partially losing the thickness. And the thin part 14 is extended in the outer edge direction from the inner edge of a bending part. Further, this thin portion 14 does not appear on the outer surface side of the bent portion of the stent base 2 and does not have any influence on the outer surface.
As shown in FIG. 3, in the stent 1 of this embodiment, the thin-walled portion 14 extends from the inner surface side of the central portion of the bent portion and from the inner edge toward the outer edge, and spreads in a fan shape. It has become. For this reason, the thin part 14 is formed in the whole area of the inner edge side of a bending part. Moreover, as shown in FIG. 4, the edge part of the thin part 14 is located in the centerline P vicinity of the line width H1 of the bending parts 21 and 22. As shown in FIG. Moreover, this thin part 14 spreads in a fan shape with a substantially constant width. Further, in this embodiment, the portions where the thin portions 14 of the bent portions 21 and 22 are provided have a substantially constant thickness. Further, the bent portion of the thin-walled portion forming portion is in a state where the inner surface side is scraped off, and the outer surface of the bent portion is continuously continuous with other portions of the stent base. That is, the thin portion is formed by a defect portion formed on the inner surface side of the bent portion, and does not appear on the outer surface side.

  And the bending parts 21 and 22 have said thin part 14, Therefore The neutral surface K of a bending part is located in the outer edge side rather than the centerline P of the line width H1 of a bending part. The bent portions 21 and 22 are deformed so as to be expanded when the stent is expanded. At this time, compressive strain is generated on the outer edge side of the bent portion 21, and tensile strain is generated on the inner edge side. And in the intermediate part of an outer edge and an inner edge, the neutral surface which neither a compressive strain nor a tensile strain arises exists. If the thin portion is not formed in the bent portion, the neutral surface is located on the center line P of the line width of the bent portion. Then, by providing the thin wall portion 14 and positioning the neutral surfaces K of the bent portions 21 and 22 on the outer edge side from the center line P of the line width of the bent portion, a portion where compression strain occurs (in other words, compression) The surface area of the portion where the strain occurs can be reduced, and the peeling of the physiologically active substance-containing resin layer 3 due to the deformation due to the compressive strain of the bent portion is suppressed. In addition, by providing the thin-walled portion 14 and positioning the neutral plane K of the bent portions 21 and 22 on the outer edge side from the center line P of the line width of the bent portion, a portion where tensile strain occurs when the stent is expanded (in other words, tensile The surface area of the portion where strain occurs) increases, but the deformation due to tensile strain is not large compared to compressive strain, and the bioactive substance-containing resin layer is also a resin layer, so it follows the tensile strain. No peeling occurs. Further, in this embodiment, since the thin portion spreads in a fan shape with a predetermined width, the region where the thin portion is formed is wide, and the neutral surface K is a bent portion in almost the entire bent portion. It is located on the outer edge side from the center line P of the line width. Further, it is preferable that one end of the thin portion 14 is positioned at the inner edge of the bent portion, and the other end is positioned near the center line of the line width of the bent portion or on the outer edge side from the center line.

And when providing the thin part 14 of a form as shown in FIG.
H1 (line width on the outer surface side of the bent portion) / H2 (line width on the inner surface side of the bent portion) ≧ 2
It is preferable that
Also,
B1 (thickness of the outer edge of the bent portion) / B2 (thickness of the thin portion of the bent portion) ≧ 2
It is preferable that
By doing so, the neutral plane K of the bent portion is positioned at the midpoint between the center line P of the line width H1 of the bent portion and the outer edge or on the outer edge side, and therefore, compressive strain occurs when the stent is expanded. The portion can be reduced.

Further, the form of the thin part formed in the bent part (the form in the thickness direction) is not limited to the constant thickness as described above, as in the thin part 14a shown in FIG. The wall thickness may increase continuously from the inner edge of the bent portion toward the outer edge. Moreover, like the thin part 14b shown in FIG. 6, thickness may become thick in steps toward the outer edge direction from the inner edge of a bending part.
Further, the shape (surface form) of the thin portion formed in the bent portion is not limited to the above-described fan shape, but a crescent shape such as the thin portion 14c shown in FIG. 7, shown in FIG. A rectangular shape such as the thin portion 14d or a circular shape such as the thin portion 14e shown in FIG. 9 may be used.

Then, the one end side bent portion 21 and the other end side bent portion 22 are bent portions which are deformed when the stent 1 is expanded, and the bent portions covered with the bioactive substance-containing resin layer 3 are, as described above, Although it is desirable that all the bent portions 21 and 22 have the thin-walled portion 14, more than half of the bent portions 21 and 22 may have the thin-walled portion 14, and preferably 70 of the bent portion that deforms when expanded. % Or more preferably has a thin portion, more preferably 80% or more, and particularly preferably 90% or more. Moreover, the thin part 14 does not need to be provided in the bent part where the physiologically active substance-containing resin layer 3 is not covered.
Further, in the stent 1 of this embodiment, the thin-walled portion 14 is provided in the bent portion which is the one-end-side bent portion and the other-end-side bent portion but is not a free end by being connected by the connecting portion. Absent. This is because the respective bent portions are integrated by being connected by the connecting portion, so that the portion is less likely to be distorted when the stent is expanded. In addition, you may provide a thin part also in these bending parts.

In addition, as the stent base 2 of the above-described embodiment, a stent base that does not substantially deform when the stent is expanded or has a bent portion with a small amount of deformation may be used. A bent portion that does not substantially deform during expansion or has a small amount of deformation may not be provided with a thin portion. Specifically, a stent substrate 10 as shown in FIGS. 11 to 13 may be used.
In the stent base 10, similarly to the stent base 2 described above, a plurality of wavy annular bodies 5 are arranged so as to be adjacent to each other in the axial direction, and each is connected by a connecting portion 13. The number of wavy line-like annular bodies 5 forming the stent substrate 10 is 14 in the one shown in FIGS. The number of wavy annular bodies 5 varies depending on the length of the stent, and is preferably 4 to 50, and more preferably 10 to 35.

Each wavy annular body 5 includes a plurality of one-end bent portions 21 and 21a having apexes on one end side in the axial direction of the stent base 10 and a plurality of other apexes on the other end side in the axial direction of the stent base 10. While having the end side bending parts 22 and 22a, it is comprised by the endless wavy body which continued cyclically | annularly. The one end side bent portions and the other end side bent portions in the annular body 5 are alternately formed, and the numbers thereof are the same.
The total number of the one-end-side bent portions 21 and the one-end-side bent portions 21a in one wavy annular body 5 is 8 in the case shown in FIG. Similarly, the total number of the other-end-side bent portions 22 and the other-end-side bent portions 22a in one wavy annular body 5 is also eight. The number of the one end side bent portions and the other end side bent portions in the wavy annular body 5 is preferably 4 to 12, and particularly preferably 6 to 10. The axial length of the wavy annular member 5 is preferably 0.5 to 2.0 mm, and particularly preferably 0.9 to 1.5 mm.
As shown in FIG. 13, the one end side bent portion 21 and the other end side bent portion 22 are greatly deformed when the stent is expanded, but the one end side bent portion 21a and the other end side bent portion 22a are changed when the stent is expanded. It is not substantially deformed or has a small amount of deformation. As shown in FIGS. 11 to 13, the thin portion 14 is provided in the one end side bent portion 21 and the other end side bent portion 22 which are greatly deformed when the stent is expanded. The other end side bent portion 22a is not provided. In addition, you may provide a thin part also in the one end side bending part 21a and the other end side bending part 22a.

As shown in FIGS. 11 and 12, the wavy annular body 5 is connected to one end of the parallel linear portion 41 parallel to the axial direction of the stent via the bent portion 21a, and at least the stent substrate 10 A first inclined linear portion 42 that is inclined at a predetermined angle with respect to the central axis of the stent base 10 at the time of expansion, and one end of the first inclined linear portion 42 is connected to the bent portion 22; An inclined linear portion (in this embodiment, an inclined curved portion) 43 extending obliquely at a predetermined angle with respect to the central axis is connected to one end of the inclined curved portion 43 via the bent portion 21, and at least a stent substrate A plurality of deformed M-shaped linear portions composed of four linear portions of the second inclined linear portion 44 that is inclined at a predetermined angle with respect to the central axis of the stent base 10 when the ten is expanded. The adjacent deformed M-shaped linear portions are connected by a bent portion 22a that connects one end of the second inclined linear portion 44 and the other end of the parallel linear portion 41, so that an endless wavy annular body is formed. 5 is constituted.
As shown in FIG. 11, in the wavy annular body 5, the bent portion 21 located on one end side of the inclined curved portion 43 is in a state of projecting to one end side from the other end-side bent portion 21 a. . Similarly, in the wavy annular body 5, the bent portion 22 located on the other end side of the inclined curved portion 43 is in a state of protruding from the other end side bent portion 22 a to the other end side. In the stent substrate 10 of this embodiment, one wavy annular body 5 is constituted by four deformed M-shaped linear portions. In addition, it is preferable that the one wavy-line annular body 5 is comprised by 3 to 5 deformation | transformation M-shaped linear parts.
Adjacent wavy-line annular bodies 5 are connected by a connecting portion 13. In particular, in the stent substrate 10 of this embodiment, the ends of the parallel straight portions 41 of the adjacent wavy line-like annular bodies 5 are connected to each other by the short and connecting portions 13. Moreover, in the stent base | substrate 10 of this Example, the two parallel linear parts 41 connected by the connection part 13 are substantially linear form.

In all the above-described stents, the stent preferably has a non-expanded diameter of about 0.8 to 1.8 mm, and more preferably 0.9 to 1.4 mm. The length of the stent when not expanded is preferably about 9 to 40 mm. Moreover, about 0.7-2.0 mm is suitable for the length of one wavy annular body. Further, the number of bent portions on one end side and the other end side of one wavy annular body is preferably 4-8, and particularly preferably 5-7. Moreover, as a number of cyclic bodies, 4-20 are suitable. The diameter of the stent during molding (before compression) is preferably about 1.5 to 3.5 mm, and more preferably 2.0 to 3.0 mm. Further, the thickness of the stent is preferably about 0.05 to 0.15 mm, particularly preferably 0.08 to 0.12 mm, and the width of the linear component is 0.07 to 0.00. About 15 mm is preferable, and 0.08 to 0.13 mm is particularly preferable.
As a material for forming the stent substrate, a material having a certain degree of biocompatibility is preferable. For example, stainless steel, tantalum or tantalum alloy, platinum or platinum alloy, gold or gold alloy, cobalt base alloy such as cobalt chrome alloy, etc. are considered. It is done. Moreover, after producing the stent shape, precious metal plating (gold, platinum) may be performed. As stainless steel, SUS316L having the most corrosion resistance is suitable.

The stent substrate is preferably chamfered. As a method for chamfering a stent, after forming the stent into a final shape, it can be performed by chemical polishing, electrolytic polishing or mechanical polishing. The chemical polishing is preferably performed by dipping in a stainless chemical polishing solution. The stainless steel chemical polishing liquid is not particularly limited as long as it can dissolve stainless steel. For example, a mixed liquid composed of hydrochloric acid and nitric acid is used as a basic component, and an organic sulfur compound for adjusting the dissolution rate, smoothing, and imparting gloss. And those to which a surfactant is added are preferred.
Furthermore, it is preferable to anneal after producing the final shape of the stent. By performing the annealing, the flexibility and plasticity of the entire stent are improved, and the indwellability in the bent blood vessel is improved. Compared to the case without annealing, the force that tries to restore the shape before expansion after expanding the stent, especially the force that tries to return to the linear shape when it expands at the bent blood vessel site, is reduced. The physical stimulation applied to the inner wall of the blood vessel can be reduced, and the factor of restenosis can be reduced. Annealing is performed by heating to 900 to 1200 ° C. in an inert gas atmosphere (for example, a mixed gas of nitrogen and hydrogen) and then slowly cooling so that an oxide film is not formed on the stent surface. preferable.

And the stent of this invention is equipped with the bioactive substance containing resin layer 3 which coat | covers the whole outer surface or the outer surface of the stent base | substrates 2 and 10 partially. As shown in FIG. 4, the physiologically active substance-containing resin layer 3 covers the entire stent substrate including the outer surface of the bent portion and only the outer surface. As shown in FIG. 4, the physiologically active substance-containing resin layer 3 preferably covers the entire outer surface of the stent substrate including the outer surface of the bent portion, but an outer surface portion that is not partially covered is formed. It may be. The physiologically active substance-containing resin layer 3 preferably covers 70% or more of the outer surface of the stent substrate, more preferably 80% or more, and particularly preferably 90% or more.
The bioactive substance-containing resin layer 3 is preferably formed of a biodegradable polymer containing a bioactive substance.
The biodegradable polymer is not particularly limited as long as it is enzymatically or non-enzymatically degraded in vivo and the degradation product does not show toxicity. For example, polylactic acid, polyglycolic acid, polylactic acid-polyglycol Acid copolymer, polycaprolactone, polylactic acid-polycaprolactone copolymer, polyorthoester, polyphosphazene, polyphosphate ester, polyhydroxybutyric acid, polymalic acid, poly α-amino acid, collagen, gelatin, laminin, heparan sulfate, fibronectin Vitronectin, chondroitin sulfate, hyaluronic acid, polypeptide, chitin, chitosan and the like can be used.

  Further, a surface treatment may be performed on the outer surface of the stent substrate in order to enhance the adhesion with the resin layer. As the surface treatment, there is a method of coating the surface with a material having high affinity as a primer. Although various materials can be used as the primer material, the most preferable one is a silane coupling agent having a hydrolyzable group and an organic functional group. The silanol group generated by the decomposition of the hydrolyzable group (for example, alkoxy group) of the silane coupling agent is bonded to the surface of the joining portion (free end portion) of the metal easily deformable portion by a covalent bond or the like. The organic functional group (for example, epoxy group, amino group, mercapto group, vinyl group, methacryloxy group) can be bonded to the polymer in the resin adhesive layer by a chemical bond. Specific examples of the silane coupling agent include γ-aminopropylethoxysilane and γ-glycidoxypropylmethyldimethoxysilane. Examples of primer materials other than silane coupling agents include organic titanium coupling agents, aluminum coupling agents, chromium coupling agents, organic phosphoric acid coupling agents, organic vapor deposition films such as polyparaxylene, and cyanoacrylates. Adhesives, polyurethane-based paste resins, and the like. In addition, it is preferable not to use a primer.

Further, a physiologically active substance may be contained in the material for forming the joint.
Physiologically active substances include agents that suppress intimal thickening, anticancer agents, immunosuppressive agents, antibiotics, anti-rheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, calcium antagonists, anti-high fats Antihypertensive agent, anti-inflammatory agent, integrin inhibitor, antiallergic agent, antioxidant, GPIIbIIIa antagonist, retinoid, flavonoid and carotenoid, lipid improver, DNA synthesis inhibitor, tyrosine kinase inhibitor, antiplatelet agent, vascular smoothing Muscle growth inhibitors, anti-inflammatory drugs, biological materials, interferons and epithelial cells generated by genetic engineering are used. And you may use 2 or more types of mixtures, such as said chemical | medical agent.
As the anticancer agent, for example, vincristine, vinblastine, vindesine, irinotecan, pirarubicin, paclitaxel, docetaxel, methotrexate and the like are preferable. As an immunosuppressant, for example, sirolimus, tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, gusperimus, mizoribine and the like are preferable. As the antibiotic, for example, mitomycin, adriamycin, doxorubicin, actinomycin, daunorubicin, idarubicin, pirarubicin, aclarubicin, epirubicin, pepromycin, dinostatin styramer and the like are preferable. As the anti-rheumatic agent, for example, methotrexate, sodium thiomalate, penicillamine, lobenzalit and the like are preferable. As the antithrombotic drug, for example, heparin, aspirin, antithrombin preparation, ticlopidine, hirudin and the like are preferable. As the HMG-CoA reductase inhibitor, for example, cerivastatin, cerivastatin sodium, atorvastatin, nisvastatin, itavastatin, fluvastatin, fluvastatin sodium, simvastatin, lovastatin, pravastatin and the like are preferable. As the ACE inhibitor, for example, quinapril, perindopril erbumine, trandolapril, cilazapril, temocapril, delapril, enalapril maleate, lisinopril, captopril and the like are preferable. As the calcium antagonist, for example, nifedipine, nilvadipine, diltiazem, benidipine, nisoldipine and the like are preferable. As the antihyperlipidemic agent, for example, probucol is preferable. As the antiallergic agent, for example, tranilast is preferable. As the retinoid, for example, as the all-trans retinoic acid flavonoid and carotenoid, for example, catechins, particularly epigallocatechin gallate, anthocyanins, proanthocyanidins, lycopene, β-carotene and the like are preferable. As the tyrosine kinase inhibitor, for example, genistein, tyrphostin, arbustatin and the like are preferable. As the anti-inflammatory agent, for example, steroids such as dexamethasone and prednisolone are preferable. As the biological material, for example, EGF (epidermal growth factor), VEGF (vascular endothelial growth factor), HGF (hepatocyte growth factor), PDGF (platelet derived growth factor), bFGF (basic fibroblast growth factor) and the like are preferable.

Next, the living organ dilator according to the present invention will be described with reference to embodiments shown in the drawings.
FIG. 14 is a partially omitted front view of the living organ dilator according to the embodiment of the present invention.
FIG. 15 is an enlarged partial cross-sectional view of the distal end portion of the living organ dilator shown in FIG.
FIG. 16 is an explanatory diagram for explaining the operation of the living organ dilator according to the embodiment of the present invention.
The living organ dilator 100 of the present invention encloses a tubular shaft body 102, a foldable and expandable balloon 103 provided at the distal end of the shaft body 102, and a balloon 103 in a folded state. And a stent 1 that is expanded by expansion of the balloon 103.
And as the stent 1, the stent 1 mentioned above and the stent of all the examples mentioned above can be used.
A living organ expanding device 100 of this embodiment includes the above-described stent 1 and a tube-shaped living organ expanding device main body 101 to which the stent 1 is attached.
The living organ expanding instrument main body 101 includes a tube-shaped shaft main body 102 and a foldable and expandable balloon 103 provided at the distal end of the shaft main body. The stent 1 includes the balloon 103 in a folded state. It is mounted so as to be encapsulated and expanded by expansion of the balloon 103.

As the stent 1, the stents of all the embodiments described above can be used. The stent used here is a so-called balloon expandable stent that has a diameter for insertion into a lumen in a living body and is expandable when a force that expands radially from the inside of the tubular body is applied. Used.
In the living organ dilator 100 of this embodiment, as shown in FIG. 14, the shaft main body 102 has one end opened at the tip of the shaft main body 102 and the other end at the rear end of the shaft main body 102. An opening guide wire lumen 115 is provided.
The living organ expanding instrument main body 101 includes a shaft main body 102 and a stent expansion balloon 103 fixed to the distal end of the shaft main body 102, and the stent 1 is mounted on the balloon 103. The shaft body 102 includes an inner tube 112, an outer tube 113, and a branch hub 110.

As shown in FIG. 15, the inner tube 112 is a tube body including a guide wire lumen 115 for inserting a guide wire therein. The inner tube 112 has a length of 100 to 2500 mm, more preferably 250 to 2000 mm, and an outer diameter of 0.1 to 1.0 mm, more preferably 0.3 to 0.7 mm, and a wall thickness of 10 to 10. It is 250 micrometers, More preferably, it is 20-100 micrometers. The inner tube 112 is inserted into the outer tube 113, and the tip of the inner tube 112 protrudes from the outer tube 113. A balloon expanding lumen 116 is formed by the outer surface of the inner tube 112 and the inner surface of the outer tube 113, and has a sufficient volume. The outer tube 113 is a tube body in which the inner tube 112 is inserted and the tip is located at a portion slightly retracted from the tip of the inner tube 112.
The outer tube 113 has a length of 100 to 2500 mm, more preferably 250 to 2000 mm, and an outer diameter of 0.5 to 1.5 mm, more preferably 0.7 to 1.1 mm, and a wall thickness of 25 to 25 mm. It is 200 μm, more preferably 50 to 100 μm.
In the living organ dilator 100 of this embodiment, the outer tube 113 is formed by the distal end side outer tube 113a and the main body side outer tube 113b, and both are joined. The distal end side outer tube 113a has a tapered diameter at a portion closer to the distal end than the joint portion with the main body side outer tube 113b, and the distal end side has a smaller diameter than the tapered portion.

The outer diameter at the small diameter portion of the distal end side outer tube 113a is 0.50 to 1.5 mm, preferably 0.60 to 1.1 mm. Further, the base end portion of the distal end side outer tube 113a and the outer diameter of the main body side outer tube 113b are 0.75 to 1.5 mm, preferably 0.9 to 1.1 mm.
The balloon 103 has a front end side joint portion 103a and a rear end side joint portion 103b. The front end side joint portion 103a is fixed at a position slightly rear end side from the front end of the inner tube 112, and the rear end side joint portion 103b. Is fixed to the tip of the outer tube. The balloon 103 communicates with the balloon expansion lumen 116 in the vicinity of the proximal end portion.
As a material for forming the inner tube 112 and the outer tube 113, a material having a certain degree of flexibility is preferable. For example, polyolefin (for example, polyethylene, polypropylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, etc.) Further, thermoplastic resins such as polyvinyl chloride, polyamide elastomer and polyurethane, silicone rubber, latex rubber and the like can be used, preferably the above-mentioned thermoplastic resin, more preferably polyolefin.

As shown in FIG. 15, the balloon 103 is foldable, and can be folded on the outer periphery of the inner tube 112 when not expanded. As shown in FIG. 16, the balloon 103 has an expandable portion that is a cylindrical portion (preferably, a cylindrical portion) having substantially the same diameter so that the attached stent 1 can be expanded. The substantially cylindrical portion may not be a complete cylinder, but may be a polygonal column. As described above, the balloon 103 is liquid-tightly fixed to the inner tube 112 with the front end side joint portion 103a and the rear end side joint portion 103b to the front end of the outer tube 113 with an adhesive or heat fusion. . Further, in this balloon 103, the space between the expandable portion and the joint portion is formed in a tapered shape.
The balloon 103 forms an expansion space 103 c between the inner surface of the balloon 103 and the outer surface of the inner tube 112. The expansion space 103c communicates with the expansion lumen 116 at the entire periphery at the rear end. In this way, the rear end of the balloon 103 communicates with the expansion lumen having a relatively large volume, so that the expansion fluid can be reliably injected into the balloon from the expansion lumen 116.

As a material for forming the balloon 103, a material having a certain degree of flexibility is preferable. For example, polyolefin (for example, polyethylene, polypropylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, cross-linked ethylene-vinyl acetate). Copolymer), polyvinyl chloride, polyamide elastomer, polyurethane, polyester (for example, polyethylene terephthalate), thermoplastic resin such as polyarylene sulfide (for example, polyphenylene sulfide), silicone rubber, latex rubber, and the like. In particular, a stretchable material is preferable, and the balloon 103 is preferably biaxially stretched having high strength and expansion force.
As the size of the balloon 103, the outer diameter of the cylindrical portion (expandable portion) when expanded is 2 to 4 mm, preferably 2.5 to 3.5 mm, and the length is 10 to 50 mm, preferably 20-40 mm. Moreover, the outer diameter of the front end side joint portion 103a is 0.9 to 1.5 mm, preferably 1 to 1.3 mm, and the length is 1 to 5 mm, preferably 1 to 1.3 mm. Moreover, the outer diameter of the rear end side joint portion 103b is 1 to 1.6 mm, preferably 1.1 to 1.5 mm, and the length is 1 to 5 mm, preferably 2 to 4 mm.

As shown in FIGS. 15 and 16, the living organ dilator 100 has two Xs fixed to the outer surface of the shaft main body at positions corresponding to both ends of the cylindrical portion (expandable portion) when expanded. Line contrast members 117 and 118 are provided. In addition, it is good also as what has two X-ray contrast contrast members fixed to the outer surface of the shaft main-body part 102 (in this embodiment, the inner pipe | tube 112) of the position which becomes the both ends of the predetermined length of the center part of the stent 1. FIG. Furthermore, it is good also as what provides the single X-ray contrast property member fixed to the outer surface of the shaft main-body part of the position used as the center part of a stent.
The X-ray contrast members 117 and 118 are preferably ring-shaped members having a predetermined length, or those obtained by winding a linear body in a coil shape, and the forming material is, for example, gold, platinum, tungsten, or the like. Those alloys or silver-palladium alloys are suitable.
The stent 1 is attached so as to encapsulate the balloon 103. The stent is manufactured by processing a metal pipe having a smaller diameter than that at the time of stent expansion and an inner diameter larger than the outer diameter of the folded balloon. Then, a balloon is inserted into the manufactured stent, and a uniform force is applied to the outer surface of the stent inward to reduce the diameter, thereby forming a product-state stent. That is, the above stent 1 is completed by compression mounting on the balloon.

A linear rigidity imparting body (not shown) may be inserted between the inner tube 112 and the outer tube 113 (within the balloon expansion lumen 116). The rigidity imparting body prevents extreme bending of the main body 102 of the living organ expanding device 100 at the bent portion without significantly reducing the flexibility of the living organ expanding device 100, and the distal end of the living organ expanding device 100. Easy to push the part. It is preferable that the tip of the rigidity imparting body has a smaller diameter than other parts by a method such as polishing. Moreover, it is preferable that the rigidity imparting body has the tip of the small diameter portion extending to the vicinity of the tip of the outer tube 113. The rigidity imparting body is preferably a metal wire, and is preferably an elastic metal such as stainless steel having a wire diameter of 0.05 to 1.50 mm, preferably 0.10 to 1.00 mm, a superelastic alloy, etc. Is a high-strength stainless steel for springs and a superelastic alloy wire.
In the living organ dilator 100 of this embodiment, as shown in FIG. 14, a branch hub 110 is fixed to the proximal end. The branch hub 110 has a guide wire inlet 109 that communicates with the guide wire lumen 115 to form a guide wire port, and communicates with the inner tube hub fixed to the inner tube 112 and the balloon expansion lumen 116, and the injection port 111. And an outer tube hub fixed to the outer tube 113. The outer tube hub and the inner tube hub are fixed to each other. As a material for forming the branch hub 110, a thermoplastic resin such as polycarbonate, polyamide, polysulfone, polyarylate, and methacrylate-butylene-styrene copolymer can be preferably used.
Note that the structure of the living organ dilator is not limited to the above, and may have a guide wire insertion port communicating with the guide wire lumen at an intermediate portion of the living organ dilator.

DESCRIPTION OF SYMBOLS 1 In vivo indwelling stent 2 Stent base | substrate 3 Physiologically active substance containing resin layer 5 Ring body 13 Connection part 14 Thin part 21 One end side bending part 22 The other end side bending part 100 Biological organ dilator

Claims (12)

An in-vivo stent that is formed into a substantially tubular body, has a diameter for insertion into a lumen in a living body, and expands when a force spreading radially from the inside is applied,
The stent is formed of a linear body having a predetermined line width, and has a plurality of one-end bent portions having apexes on one end side in the axial direction of the stent and a plurality of apexes on the other end side in the axial direction of the stent. A stent base comprising a plurality of annular bodies having a bent portion at the other end, and a connecting portion for connecting the adjacent annular bodies, and a physiologically active substance-containing resin partially covering the entire outer surface or the outer surface of the stent base With layers,
The one-end-side bent portion and the other-end-side bent portion, which are deformed when the stent is expanded, and more than half of the bent portions covered with the physiologically active substance-containing resin layer, In vivo, characterized in that it has a thin portion formed by partially missing the inner surface side of the bent portion, and the thin portion extends from the inner edge of the bent portion in the outer edge direction. Indwelling stent. The in-vivo stent according to claim 1, wherein the bent portion of the portion having the thin-walled portion has a neutral surface located on the outer edge side of the center line of the line width of the bent portion. The in-vivo indwelling stent according to claim 1 or 2, wherein the thin-walled portion extends from the inner side of the central portion of the bent portion and from the inner edge toward the outer edge. The thin-walled portion has one end positioned at the inner edge of the bent portion and the other end positioned near the center line of the line width of the bent portion or on the outer edge side from the center line. The stent for in-vivo indwelling described. 5. The bent portion that is a bent portion that is deformed when the stent is expanded and that is 80% or more of the bent portion that is covered with the physiologically active substance-containing resin layer has the thin portion. The stent for in-vivo indwelling. The in-vivo stent according to any one of claims 1 to 5, wherein the thin portion is any one of a fan shape, a crescent shape, a circular shape, and a rectangular shape. The in-vivo indwelling stent according to any one of claims 1 to 6, wherein a portion of the bent portion where the thin portion is provided has a substantially constant thickness. The portion of the bent portion where the thin portion is provided has a thickness that increases continuously or stepwise from the inner edge of the bent portion toward the outer edge. In vivo indwelling stent. The stent base has a bent portion that does not substantially deform or has a small amount of deformation when the stent is expanded, and the thin portion has a bent portion that does not substantially deform or has a small amount of deformation when the stent is expanded. The stent for in-vivo indwelling in any one of Claim 1 thru | or 8 which is not provided. The in-vivo stent according to any one of claims 1 to 9, wherein the bioactive substance-containing resin layer is formed of a biodegradable polymer containing a bioactive substance. The in-vivo indwelling stent according to any one of claims 1 to 10, wherein the annular body is an endless continuous in an annular shape having a linear portion connecting the one end side bent portion and the other end side bent portion. . The tubular shaft main body, a foldable and expandable balloon provided at the tip of the shaft main body, and the balloon in a folded state are mounted so as to enclose the balloon. A biological organ dilating device comprising the above-described stent.

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