JP7199950B2 - Biodegradable stent and medical device containing same - Google Patents

Description

The present invention relates to biodegradable stents for insertion into living body ducts such as digestive tracts, bile ducts, pancreatic ducts, blood vessels, ureters, and trachea, and medical devices including the same. In particular, the present invention relates to a self-expanding biodegradable stent with improved stent end expandability and a medical device comprising the same.

A body lumen is narrowed due to various causes, and stent placement is often performed as a treatment for this. In recent years, attention has been paid to biodegradable stents, which remain in the stenosis site for a certain period of time, but then decompose and disappear from the body, for their safety and the like.

However, the self-expanding force of biodegradable stents made of plastic resin is low and often insufficient compared to metallic stents made of shape memory alloys and the like. In particular, if the end of the stent is insufficiently expanded, there is a risk of obstruction of passage in the tube.
As a method for reinforcing the expansion force of biodegradable stents, the use of elastic filaments and the like has been proposed (Patent Documents 1 to 3). However, although these methods can increase the expansion force of the central portion of the stent, they have not been able to ensure sufficient expandability at the ends of the stent. As a method to improve this, a method of using an elastic connecting member or a shape memory alloy at the ends of the stent has been proposed (Patent Documents 4 and 5).

Japanese Patent Publication No. 4-47575 Japanese Patent Publication No. 2004-528115 WO2016-035757 JP 2016-146869 A JP 2017-29387 A

However, conventional self-expanding biodegradable stents are not sufficiently expandable at the end of the stent, and a simple and reliable method for expanding the end of the stent has been desired.

The present invention is intended to solve such problems, and provides a biodegradable stent and a medical device including the same that can reliably expand the end of the stent.

The biodegradable stent of the present invention is a biodegradable stent comprising a stent body in which a plurality of filament threads made of a biodegradable polymer are braided into a cylindrical braid, wherein the length direction including the vicinity of each end of the stent body is One end of the elastic thread is fixed near one end of the stent body and the other end is fixed near the other end of the stent body The elastic thread is fixed to the stent-constituting thread on the central side to form a fixed point or intersect to form a point of contact, and between both ends of the stent and the fixed point or point of contact on the central side of the stent. The elastic thread is characterized in that it is arranged outside the stent.
Another biodegradable stent of the present invention is a biodegradable stent comprising a stent body in which a plurality of filament threads made of a biodegradable polymer are braided into a cylindrical braid, wherein a length including the vicinity of each end of the stent body is provided. An elastic thread is arranged in at least a part of the longitudinal direction, one end of the elastic thread is fixed near the end of the stent main body, and the other end is attached to the stent-constituting thread on the central side of the end of the stent main body. and the elastic thread between both ends of the stent and the fixing point on the central side of the stent is arranged outside the stent.

A medical device of the present invention is characterized in that the biodegradable stent is mounted on a delivery system.

According to the configuration of the present invention, since the contractile force of the elastic thread acts on the vicinity of each end of the stent main body to widen it outward, it is possible to reliably expand the end of the stent main body. Moreover, since the elastic thread is fixed to the main body of the stent, there is no need to use a special member, and expansion can be achieved by a very simple method.

FIG. 1 is a schematic side view of a stent according to one embodiment of the invention. FIG. 2 is a schematic side view of a stent in another embodiment of the present invention, in which the contact point between the elastic thread and the thread constituting the main body of the stent is positioned half the length of the stent from the end of the main body of the stent. FIG. 3 shows a still further embodiment of the present invention in which the contact points between the elastic threads and the threads constituting the main body of the stent are positioned at ⅓ of the length of the stent from the ends of the main body of the stent, and the elastic threads constitute the stent between the contact points. FIG. 2 is a schematic side view of a stent placed within a braid; FIG. 4 is a schematic side view of a stent with elastic threads positioned outwardly near each end of the stent body in accordance with yet another embodiment of the present invention. FIG. 5 illustrates yet another embodiment of the present invention in which the elastic yarns are placed on the outside of the stent body and fixed near each end, and the filament yarn ends forming the braid have two longitudinal rows of connecting points. 1 is a schematic side view of stents arranged side by side; FIG. FIG. 6 is a schematic explanatory diagram showing a braid manufacturing apparatus of the same. FIG. 7A is a schematic partial explanatory view of the braid manufacturing apparatus, and FIG. 7B is an operation diagram showing the movement of the bobbin. FIG. 8 is a schematic side view of the same delivery system carrying a stent. FIG. 9A is a side view photograph of the stent of Example 1 before mounting the delivery system, FIG. 9B is a side view view immediately after release from the delivery system, and FIG. 9C is a side view view 3 minutes after release from the delivery system. FIG. 10A is a side view photograph of the stent of Example 2 before mounting the delivery system, FIG. 10B is a side view view immediately after release from the delivery system, and FIG. 10C is a side view view 3 minutes after release from the delivery system. FIG. 11A is a side view photograph of the stent of Comparative Example 1 before mounting the delivery system, FIG. 11B is a side view view immediately after release from the delivery system, and FIG. 11C is a side view view 3 minutes after release from the delivery system. FIG. 12A is a side view photograph of the stent of Comparative Example 2 before mounting the delivery system, FIG. 12B is a side view view immediately after release from the delivery system, and FIG. 12C is a side view view 3 minutes after release from the delivery system. FIG. 13A is a side view photograph of the stent of Comparative Example 3 before mounting the delivery system, FIG. 13B is a side view view immediately after release from the delivery system, and FIG. 13C is a side view view 3 minutes after release from the delivery system. FIG. 14 is a photograph of the appearance of the stent before placement in Example 3 of the present invention. FIG. 15 is a photograph of the appearance 10 minutes after the stent was indwelled in the small intestine of the minipig in the animal experiment of Example 3 of the present invention.

The biodegradable stent of the present invention includes a stent body in which a plurality of filament threads made of a biodegradable polymer are braided into a cylindrical braid, and elastic threads are arranged on the outside of the stent body in the longitudinal direction. . The elastic threads are disposed along at least a portion of the length of the stent body, including near each end. One end of this elastic thread is fixed near the end of the stent body, and the other end is fixed at some part of the stent body. In the state where the diameter of the main body of the stent is reduced, tension is applied to the elastic thread. As a result, when the stent body is expanded from a contracted state, the contractile force of the elastic thread exerts a force to spread the stent body outward in the vicinity of each end of the stent body, so that the ends of the stent body can be reliably expanded. .

The polymer constituting the biodegradable filament yarn includes polyglycolic acid, poly-L-lactic acid, poly-D-lactic acid, polycaprolactone, polydioxanone, polyethylene glycol, and biodegradable synthetic polymers such as copolymers thereof, collagen, It is preferably at least one selected from biodegradable natural polymers such as gelatin, glycosaminoglycan, chitin, chitosan, hyaluronic acid, alginic acid and silk fibroin, spider silk fibroin. It is said that biodegradable synthetic polymers take about 2 weeks for polyglycol, about 6 months for polylactic acid, and 1 to 2 years for polycaprolactone. , polymer blend, molecular weight and crystallinity. As for the biodegradable natural polymer, the degradation period in vivo can be adjusted by controlling the molecular weight, controlling the structure, imparting a crosslinked structure, or the like.

The filament yarns preferably comprise 16 (16 strokes) or more, more preferably 24 (24 strokes) or more, and still more preferably 32 (32 strokes) or more. The upper limit is preferably 64 lines (64 shots) or less. Within the above range, each filament thread forms a spiral braid to form a braid, resulting in a stent with even higher self-expandability and deformation recovery. For the same reason, the braiding angle of each filament yarn (braiding yarn) forming the braid is preferably 30 to 80°. A preferred angle is 35-75°. If the angle of the braid is within the above range, the braid can be formed into a cylindrical shape without distortion. Here, the braiding angle means an acute angle between the length direction of the entire braid and the braiding thread direction. Also, the number of sets is 3/inch or more, preferably 4 to 18/inch. As a result, the yarn density and stitch density are high, the strength is high, and the elasticity is also high. Braided cords are divided into round and square braids, and braids braided by round beating are hollow and suitable for stents.

The diameter of the filament thread is preferably 0.15-1.0 mm, more preferably 0.15-0.8 mm, and more preferably 0.15-0.6 mm. Within the above range, a sufficient expansion force can be maintained.

The elastic thread arranged on the outside of the main body of the stent is preferably spun from biocompatible polyurethane, rubber or thermoplastic elastomer. As a biocompatible polyurethane thread, there is, for example, the trade name "Pellethane" manufactured by Lubrizol in the United States, which is a US class VI compliant product. When using polyurethane yarns, filament yarns with a diameter of 50-500 μm are preferred, and filament yarns with a diameter of 60-300 μm are more preferred. Also, a plurality of filament yarns may be bundled and used. These elastic threads are not biodegradable, but the main part of the braid of the stent of the present invention is formed of biodegradable filament threads. It will be excreted even if it contains a substance that does not have

It is preferable that the elastic thread is fixed to the braid-constituting thread at the center side of the end portion of the main body of the stent as a fixing point, or crossed (passed through) as a point of contact. As a result, even if the stent body is bent and inserted into the living body, the ends of the stent body are expanded accurately. Preferably, the fixing points or contact points are located 1/8 to 1/2 of the length of the stent from the ends of the main body of the stent. This further expands the ends of the stent body precisely.

The tension applied to the elastic thread is preferably 0.1 to 5.0 N/thread, more preferably 0.3 to 3.0 N/thread, and particularly preferably 0.5 to 2 when the diameter of the main body of the stent is reduced. .5N/book. where N is Newton. This further expands the ends of the stent body precisely.

It is preferable that 3 to 6 elastic threads are arranged at regular intervals in the circumferential direction of the main body of the stent. This will spread evenly. In addition, the biodegradable stent preferably has a diameter ratio of 5 to 10 times from the contracted state to the expanded state. As a result, sufficient performance can be exhibited as a medical device.

When the biodegradable stent is expanded from a contracted state, the rate of change with respect to the original average diameter in the longitudinal direction is preferably in the range of -15 to +30%, more preferably -10 to +25%. Range. This allows uniform self-expansion, especially self-expansion close to the original state.

At the ends of the stent main body, it is preferable that the connecting points of the ends of the filaments forming the braid are arranged in two or more rows in the longitudinal direction. More preferably, there are 2 to 4 rows of attachment points. This makes the stent easy to mount on a delivery system and easy to expand. In addition, when the stent main body is converged, the number of connecting points at the outermost end of the stent can be reduced to create a spatial margin, which makes it possible to reduce the diameter of the end, making it easier to mount on a delivery system and expand the stent. Easy effect. It also has the effect that the end of the stent tends to expand after the stent is released.

The elastic thread and the main body of the stent are preferably fixed by heat fusion, ultrasonic fusion, adhesive, or a metal or resin tube. Heat fusion and ultrasonic fusion are relatively easy to fix. One end of the elastic thread is secured near the end of the stent. Although this fixation can be fixed at the extreme ends of the stent, it is possible to expand the ends of the stent more effectively by fixing it to the crossing points of the filament threads near the ends of the stent. can be done. The set to be fixed is not limited to the endmost portion, and can be fixed up to about the third set from the endmost portion. The fixing point of the other end of the elastic thread can be changed depending on the length of the elastic thread used. Threads can be used to expand the ends of the stent.

Another method of anchoring can be by tying elastic threads to the filament threads that make up the stent. According to this method, there is no need to use a special member for fixing, and the fixation can be carried out easily. It is also possible to crimp the elastic thread and the filament thread constituting the stent using a biocompatible metal such as stainless steel, gold, platinum, platinum/palladium alloy, platinum/iridium alloy, or platinum/tungsten alloy. can be fixed.

The medical device of the present invention is a medical device containing the biodegradable stent. This medical device has the biodegradable stent converging on a delivery system.

In the simplest embodiment of the present invention, elastic threads are placed outside the stent and both ends of the elastic threads are fixed only near the ends of the stent. In this case, since the contractile force of the elastic thread acts only between the ends of the stent, the stent may bend. As a method of improving this, it is preferable to position the contact point between the elastic thread and the stent at a position 1/8 to 1/2 of the length of the stent from the end of the stent.

The contact points between the elastic thread and the stent can be made by the fixing method described above, but they may also be crossed with the filament thread forming the main body of the stent. One point of contact may be sufficient, but two or more points may be provided. When there are two or more points of contact, the elastic thread may be arranged on the outside or inside of the stent between the points of contact, or may be woven into the stent.

Description will be made below with reference to the drawings. In the following drawings, the same symbols indicate the same items. FIG. 1 is a schematic side view of a biodegradable stent 1a in one embodiment (reference example) of the present invention. The stent 1a is composed of a filament thread 2 of a braid forming a main body of the stent and elastic threads 4a to 4d arranged outside the main body of the stent. In this example, one end of the elastic threads 4a-4d is fixed near the end of the stent body, the other end is fixed at the other end of the stent body, and 5a and 5b are the fixing points of the elastic threads. It is a point. This fixation is formed by fusion. In this stent main body, the elastic threads 4a-4d are under tension when the diameter is reduced. At both ends of the main body of the stent, the ends of the filament threads 2 of the braid are fixed by fusion or the like. 3a is a fixed point at the end of the filament yarn 2;

FIG. 2 is a schematic side view of a stent 1b according to another embodiment of the present invention, in which the contact point between the elastic thread and the thread constituting the main body of the stent is positioned half the length of the stent from the end of the main body of the stent. The difference from FIG. 1 is that the elastic thread 4a is crossed (passed through) through the filament thread in the central portion of the stent main body to form the contact point 6a. The contact point 6a may be a fixed point. As a result, even if the stent body is bent and inserted into the living body, the ends of the stent body are expanded accurately.

FIG. 3 shows a further embodiment of the present invention in which the contact point between the elastic thread and the thread constituting the main body of the stent is positioned at ⅓ of the length of the stent from the end of the stent body, and the elastic thread is placed between the contact points 6a and 6b. 1 is a schematic side view of a stent 1c arranged in a braid that constitutes the . The contacts 6a, 6b may be fixed points. As a result, even if the stent body is inserted into the living body in a bent state as in FIG. 2, the ends of the stent body are expanded accurately.

FIG. 4 is a schematic side view of a stent 1d with elastic threads placed outside near each end of the stent body in accordance with yet another embodiment of the present invention. The elastic thread 4a is fixed to the filament threads forming the stent body at fixing points 5a and 5b, and the elastic thread 4b is fixed to the filament threads forming the stent body at fixing points 5c and 5d. This causes at least both ends to expand outward.

FIG. 5 illustrates yet another embodiment of the present invention in which the elastic yarns are placed on the outside of the stent body and fixed near each end, and the filament yarn ends forming the braid have two longitudinal rows of connecting points. FIG. 3 is a schematic side view of stents 1e arranged side by side. The difference from FIG. 2 is that at one end 7a of the stent main body, the connecting points 3a and 3b of the filament ends are arranged in two rows in the longitudinal direction, and at the other end 7b of the stent main body, the filament ends are arranged. The coupling points 3c, 3d are arranged in two rows in the longitudinal direction. As a result, when the main body of the stent is converged, the number of connecting points at the outermost end of the stent can be reduced, thereby creating a spatial margin and allowing the diameter of the end to be reduced. It has an easy effect. It also has the effect that the end of the stent tends to expand after the stent is released.

FIG. 6 is a schematic explanatory diagram showing a braid manufacturing apparatus of the same. This example is a schematic explanatory view showing an apparatus for manufacturing a round braid. The manufacturing apparatus 10 includes a frame 11, a bobbin (carrier) 12, a mandrel 14, and a driving device (not shown). As the bobbin 12 rotates along the solid line of the track 19 (FIG. 7B) on the base 11, the thread 13 wound around the bobbin 12 is braided on the mandrel 14 that pushes up to form a braid 17. The push-up portion 16 is composed of a hemispherical head that moves up and down in conjunction with the rotational movement of the bobbin 12 and a cylindrical (or polygonal) cylindrical portion 15 at the center thereof. The outer diameter of the cylindrical portion 15 is approximately equal to the inner diameter of the braid 17 . The braid 17 is sent to a heater and heat-set if necessary. The braided cord 17 passes through a take-out guide (pulley) 18 and is shaken off into the storage container. In the above, the mandrel 14 stroke length and the number of strokes are appropriately set. Heat setting can also be added to the braid.

FIG. 7A is a schematic partial explanatory diagram of inserting warp yarns (elastic yarns) in the manufacturing apparatus, and FIG. 7B is an operation diagram showing the movement of the bobbin. 7A-B, the bobbin 12 rotates on the solid line of the track 19 on the base 11, so that the yarn 13 wound around the bobbin 12 is braided on the mandrel 14 that pushes up, creating a braid 17. .

FIG. 8 is a schematic side view of a delivery system 20 carrying a stent 1 according to one embodiment of the invention. The system includes a hub 21, a pusher 22, a Y-connector 23, an outer sheath 24 having an inner catheter inside, on which a stent 1 is mounted on a stent-loading portion 25 of the inner catheter. It is inserted into the living body in this state.

EXAMPLES The present invention will be described in more detail below using examples and comparative examples, but the present invention is not limited to the following examples.

(Example 1)
Thirty-two monofilament threads (diameter: 0.23 mm) made of polyglycolic acid (PGA) were used to prepare a braided stent (diameter: 22 mm, length: 80 mm) using a braiding apparatus. A polyurethane elastic thread (manufactured by Lubrizol, USA, trade name "Pellethane" (diameter: 200 µm)) was placed on the stent main body outside and fixed at both ends of the stent as shown in Fig. 1 . However, as shown in FIG. 5, the connecting points of the ends of the filament yarns forming the braid were arranged in two rows in the longitudinal direction. Four polyurethane elastic threads were arranged at equal intervals on the circumference of the stent. This braided stent was mounted on a delivery system with an inner diameter of 3 mm shown in FIG. 8, and then pushed out from the delivery system. expanded to 22-27 mm larger than the diameter of the FIG. 9A shows a side photograph of the stent before mounting the delivery system, FIG. 9B shows a side photograph immediately after release from the delivery system, and FIG. 9C shows a side photograph three minutes after release from the delivery system.

(Example 2)
A braided stent was prepared in the same manner as in Example 1, except that the polyurethane elastic thread was crossed with the monofilament thread constituting the braided cord at the center of the stent as shown in FIG. This braided stent was mounted on a delivery system with an inner diameter of 3 mm and then pushed out from the delivery system. , extended to a large 22-27 mm. FIG. 10A shows a side photograph of the stent before mounting the delivery system, FIG. 10B shows a side photograph immediately after release from the delivery system, and FIG. 10C shows a side view photograph 3 minutes after release from the delivery system.

(Example 3)
Using 32 monofilament threads (0.29 mm in diameter) made of polyglycolic acid, a braided stent (19 mm in diameter, 75 mm in length) was produced using a braided cord production apparatus. Polyurethane elastic thread (manufactured by Lubrizol, USA, trade name "Pellethane" (diameter 150 μm)) is attached to this braided stent, and as shown in FIG. The contact point was placed between the elastic thread and the braid constituting the stent through the outside to the 1/3 position, and the elastic thread was passed through the braid constituting the stent between the contact points. This stent was surgically placed in the small intestine of a minipig using a delivery system with an inner diameter of 9 mm. FIG. 14 shows the appearance of the stent before placement in this example, and FIG. 15 shows the appearance 10 minutes after placement in the minipig small intestine. The diameter of the central part was 19 mm, the diameter of the end on the stomach side was 19 mm, and the diameter of the end on the anus side was 19 mm, and it was well expanded to the ends.

(Comparative example 1)
A braided stent was prepared in the same manner as in Example 1, except that a polyurethane elastic thread was arranged inside the stent. When this braided stent was mounted on a delivery system with an inner diameter of 3 mm and then pushed out from the delivery system, the stent self-expanded, but one end expanded only by about 15 mm and did not expand to its original diameter. . FIG. 11A is a side view photograph of the stent before mounting the delivery system, FIG. 11B is a side view view immediately after release from the delivery system, and FIG. 11C is a side view view 3 minutes after release from the delivery system.

(Comparative example 2)
A braided stent was prepared in the same manner as in Example 1, except that the polyurethane elastic thread was woven into the monofilaments constituting the stent braid. When this braided stent was mounted on a delivery system with an inner diameter of 3 mm and then pushed out from the delivery system, one end expanded only by about 17 mm and did not expand to its original diameter. FIG. 12A shows a side photograph of the stent before mounting the delivery system, FIG. 12B shows a side photograph immediately after release from the delivery system, and FIG. 12C shows a side photograph three minutes after release from the delivery system.

(Comparative Example 3)
A braided stent was produced in the same manner as in Example 1, except that the polyurethane elastic thread was not arranged. When this braided stent was mounted on a delivery system with an inner diameter of 3 mm and then pushed out from the delivery system, one end expanded only by about 17 mm and did not expand to its original diameter. FIG. 13A shows a side photograph of the stent before mounting the delivery system, FIG. 13B shows a side photograph immediately after release from the delivery system, and FIG. 13C shows a side view photograph 3 minutes after release from the delivery system.

The biodegradable stent of the present invention is suitable for insertion into the ducts of living organisms such as humans, pets, and livestock.

1a-1e biodegradable stent 2 filament yarns 3a-3d that make up the braid filament yarn terminal fixing points 4a-4g elastic yarns 5a-5d elastic yarn and filament yarn fixing points 6a-6b contact points of elastic yarn and filament yarn or Fixing points 7a, 7b Stent main body end 10 Braid manufacturing device 11 Base 12 Bobbin (carrier)
13 Thread 14 Mandrel 15 Cylindrical portion 16 Push-up portion 17 Braided cord 18 Guide (pulley)
19 track 20 delivery system 21 hub 22 pusher 23 Y connector 24 outer sheath 25 delivery

Claims (10)

A biodegradable stent including a stent main body in which a plurality of filament threads made of a biodegradable polymer are braided into a cylindrical braid,
An elastic thread is arranged in at least a part of the length direction including near each end of the main body of the stent,
one end of the elastic thread is fixed near one end of the stent body and the other end is fixed near the other end of the stent body,
The elastic thread is fixed to the stent-constituting thread at the center side to be a fixed point or crossed to be a point of contact,
A biodegradable stent, wherein elastic threads between both ends of the stent and fixing points or contact points on the central side of the stent are arranged outside the stent. A biodegradable stent including a stent main body in which a plurality of filament threads made of a biodegradable polymer are braided into a cylindrical braid,
An elastic thread is arranged in at least a part of the length direction including near each end of the main body of the stent,
One end of the elastic thread is fixed near the end of the stent main body, and the other end is fixed to the stent-constituting thread centrally from the end of the stent main body as a fixing point ,
A biodegradable stent, wherein elastic threads between both ends of the stent and fixing points on the central side of the stent are arranged outside the stent. 3. The biodegradable stent according to claim 1, wherein the elastic thread is spun from biocompatible polyurethane, rubber or thermoplastic elastomer. 4. The fixation point or point of contact between the elastic thread on the central side of the stent body and the stent body-constituting thread, according to claim 1 or 3 , at a position 1/8 to 1/2 of the length of the stent from the end of the stent body. Biodegradable stent. 4. The biodegradation according to claim 2 or 3, wherein the fixing point of the elastic thread on the central side of the stent body and the stent body-constituting thread is located at a position 1/8 to 1/2 of the length of the stent from the end of the stent body. sexual stent. The biodegradable stent according to any one of claims 1 to 5, wherein the tension applied to the elastic thread is 0.1 to 5.0 N/thread when the main body of the stent is contracted. The biodegradable stent according to any one of claims 1 to 6 , wherein 3 to 6 elastic threads are arranged at equal intervals in the circumferential direction of the stent main body. The biodegradable stent according to any one of claims 1 to 7, wherein the biodegradable stent has a diameter magnification from a contracted state to an expanded state ranging from 5 to 10 times. The biodegradability according to any one of claims 1 to 8, wherein the elastic thread and the stent main body are fixed by heat fusion, ultrasonic fusion, bonding with an adhesive, or a metal or resin tube. stent. A medical device comprising the biodegradable stent according to any one of claims 1 to 9 mounted in a delivery system.

Images