JP2002239013A - Stent and method of manufacturing for the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a balloon dilation type stent which is easily and inexpensively shaped from a fiber consisting of an in vivo degradation absorptive polymer material to a stent shape and a method of manufacturing for the same. SOLUTION: A stent body of the stent to be indwelt in the vessel is formed by winding the fiber bent to a corrugated or zigzag shape to a cylindrical form. The fiber is pinched and compressed by planar tools 6 and 7, by which the corrugated or zigzag molding is formed. The stent is subjected to heat treatment of at least >=2 deg.C in the forming process step.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a stent used for securing a sufficient lumen by placing it in a blood vessel such as a blood vessel, a ureter, a urethra, a lymph vessel or the like where stenosis of a living body occurs. Things.

[0002]

2. Description of the Related Art When a stenosis occurs in a blood vessel such as a coronary artery of a living body, a balloon catheter is inserted into the stenosis and the balloon is inflated to expand the blood vessel and secure a lumen. Percutaneous coronary angioplasty (PTCA) to improve blood flow has been performed. However, postoperative 3
It is estimated that approximately 40% of patients will have restenosis of the coronary arteries within a month.

[0003] In order to solve the above problems, treatment with a stent attached to a balloon has been performed. By inserting the stent into a stenosis site and expanding it with a balloon, it is possible to achieve a desired appropriate blood vessel diameter. Conventionally, this stent is made of metal, and various types of so-called coil stents and slot stents have appeared. Such a stent is made of metal and cannot be removed from the body once placed in the body, which may be disadvantageous for restenosis after placement of the stent.

Accordingly, a stent made of a biodegradable and absorbable polymer material has been devised. With such a stent,
Immediately after the stent placement, a sufficient blood vessel lumen is secured, and after a period in which the blood vessel in the stent placement part is covered with vascular endothelial cells and the reaction that promotes stenosis such as new thrombus does not occur, it is decomposed and absorbed into the living body and Will never survive.

[0005] On the other hand, when manufacturing a stent formed from fibers of a biodegradable and absorbable polymer material, there is a problem in how to provide appropriate rigidity and how to shape the stent. Heretofore, flat-mesh-shaped or zigzag-shaped fibers wound in a cylindrical shape, and self-expandable wall stents have been disclosed, but flat-mesh-shaped or wall stents have been disclosed. For example, in the case where the fiber is knitted in a cylindrical shape with an outer diameter of about 3 mm and the fibers overlap each other and the thickness increases in the inner diameter direction, and the zigzag fiber is wound in a cylindrical shape, in order to form the shape, For example, a small mold is required, and the mold is reduced in size. If the frequency of use of the mold is increased, durability is lost or the mold itself is expensive.

[0006] Therefore, it has been desired that fibers having appropriate rigidity can be easily and inexpensively shaped into a stent shape.

[0007]

SUMMARY OF THE INVENTION The present invention solves the above-mentioned problems and provides a simple and inexpensive shaping from a fiber made of a polymer material, particularly a biodegradable and absorbable polymer material, to a stent shape. It is intended to provide a balloon expandable stent obtained from the manufacturing method.

[0008]

Means for Solving the Problems The present inventor has made intensive studies for this purpose, and as a result, found that a stent can be obtained by shaping into a desired stent shape and a method of manufacturing the same by the following. Reached. (1) In a stent to be placed in a vessel of a living body, the stent body has a wavy or zigzag shape obtained by winding a fiber folded in a wavy or zigzag shape into a cylindrical shape, sandwiching the fibers in a plate-shaped jig, and compressing the fiber. A stent in which a shaped article is formed, wherein at least two heat treatments are performed in the stent forming step, and the heat treatment is performed at a temperature not lower than the glass transition of the fiber and not higher than the melting point thereof. A stent and a method for manufacturing the stent, wherein a subsequent heat treatment temperature is set to be higher than that. (2) The stent according to (1), wherein the corrugated or zigzag bent fiber is formed by sandwiching a coiled fiber with a plate-shaped jig and compressing the fiber. Its manufacturing method. (3) The stent according to (2), wherein the cross-sectional shape of the coil-shaped fiber is formed by winding it around a mold having a perfect circle or an ellipse. (4) The stent according to (2), wherein the coil-shaped fiber is formed by being tightly wound around a mold having a perfect circular or elliptical cross section and then stretched. Method. (5) The stent according to (1), wherein the fiber is a biodegradable and absorbable polymer material, and a method for producing the stent. (6) The biodegradable and absorbable polymer material is selected from polylactic acid, polyglycolic acid, polyhydroxybutyric acid, poly (ε-caprolactone) or a copolymer thereof. And a method for producing the same. (7) The stent according to any one of (1) to (6), wherein a drug is coated or contained in at least a part of the stent, and a method of manufacturing the stent. (8) The stent according to any one of (1) to (7), wherein the method for expanding the stent is a balloon expandable type, and a method for manufacturing the stent. Is achieved by

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be described below.
Further details will be described.

A stent 1 of the present invention is a stent to be placed in a vessel of a living body. As shown in FIG. 1, the stent main body is formed by winding a fiber folded in a wavy or zigzag shape into a cylindrical shape. This is a stent formed by:
This stent is characterized in that it is sandwiched between plate-shaped jigs 6 and 7 shown in FIG. 7 and compressed to form a corrugated 2 or zigzag shaped product shown in FIG. In this way, it is possible to easily produce a fiber folded in a wave-like 2 or zigzag shape, and the shape can be produced in a flat state by this production method.

[0011] The corrugated fiber 2 or zigzag-shaped fiber is wound into a cylindrical shape.
It becomes the shape of.

The plate-shaped jigs 6 and 7 for producing the corrugated or zigzag molded product can be made of metal or glass, and can sufficiently transmit a shaping temperature to be described later. Any material that does not deform when a fiber made of a molecular material is inserted may be used.

The fibers of the stent of the present invention are shown in FIGS.
The fiber 3 wound in a coil shape as shown in FIG.
And 7 are sandwiched and compressed to form fibers which are bent in a wavy 2 or zigzag shape. The coiled fiber has a desired pitch of 9 and a diameter of 1.
0, and can be formed into a desired shape.

In producing the coil-wound fiber, the fiber is wound around a rod-shaped mold 14 at a desired pitch and diameter, or after being wound tightly around a rod-shaped mold having a desired diameter. It can also be obtained by stretching to a desired pitch 9.

The cross-sectional shape of the mold 14 used to obtain the coil-wound fiber for obtaining the stent of the present invention may be a perfect circle as shown in FIG.
It is possible to use an elliptical shape (15) as shown in FIG. Circular fibers are obtained from a perfect circle and uniform ellipses are obtained from an ellipse. The cross-sectional shape of the rod-shaped mold 14 of the present invention includes
Not only the perfect circle or ellipse but also other things such as a square and a rectangle can be used. In this case, it is preferable to have a moderate roundness so as not to damage the fiber.

Further, the fiber diameter of the fiber obtained from the biodegradable and absorbable polymer material used in manufacturing the stent of the present invention is desirably 50 μm to 1000 μm.
If a stent is manufactured with fibers of 50 μm or less, the radial force for maintaining an appropriate blood vessel diameter is too small, and the
If it is 000 μm or more, for example, it may be too thick for a stenotic coronary artery, and the expandability of the balloon may be reduced. A more preferred fiber diameter is 100 to 500 μm.

In order to realize an appropriate radial force of the stent obtained by using the fiber having the above-mentioned fiber diameter, the storage elastic modulus at 37 ° C. of the fiber forming the stent of the present invention is 1 unit.
Desirably, it is 50 GPa. By measuring the elastic modulus under a dynamic environment in which vibration is applied, it is possible to evaluate the rigidity affected by pulsation in a blood vessel or the like.
More preferably, it is 3 to 30 GPa. Within this range, it is possible to realize appropriate rigidity, that is, bending rigidity, for the blood vessel. The bending stiffness is represented by the product of the second moment of area of the fiber and the Young's modulus. Here, the storage modulus is used instead of the Young's modulus. Outside the above range, the bending rigidity is too weak or too strong, and it is not possible to realize bending rigidity for maintaining an appropriate blood vessel lumen, that is, to realize radial force for maintaining an appropriate blood vessel diameter. It will be difficult. Further, in order to realize such storage elastic modulus, it is preferable to apply a treatment such as drawing and orienting the fiber obtained by the above-mentioned spinning at an appropriate draw ratio and heat treatment at an appropriate temperature.

By this operation, the biodegradable and absorbable polymer material is oriented and crystallized, and a material having a high crystallinity can be produced. Therefore, the biodegradable and absorbable polymer material is not decomposed and absorbed in a short time, and the performance of the stent can be maintained for a long time.

The stent of the present invention is formed from fibers of a polymer material. It is desirable to use a biodegradable and absorbable polymer material that is decomposed and absorbed and metabolized in vivo. By using such a biodegradable and absorbable polymer material, it can be absorbed into the body without remaining forever in the body unlike a metal stent. Even if restenosis occurs, since the stent itself has been decomposed and absorbed, it is possible to insert the stent again at the same stenosis site and place it. Therefore, the stent-in-st generated by the metallic stent
The problem of ent does not occur. The biodegradable and absorbable polymer material is selected from polylactic acid, polyglycolic acid, polyhydroxybutyric acid, poly (ε-caprolactone) or a copolymer thereof. More preferably, it is selected from polylactic acid, polyglycolic acid, and lactic acid-glycolic acid copolymer.

The fiber obtained from the biodegradable and absorbable polymer material can be obtained by a method such as melt spinning, dry spinning, and wet spinning. The weight-average molecular weight of the biodegradable and absorbable polymer material determined by the GPC method is 10,000 to 1,000,000 in order to realize appropriate molding. More preferably, 10
10,000 to 500,000. The GPC method was performed using chloroform as the mobile phase, a column temperature of 40 ° C., a flow rate of 1 ml / min, and polystyrene conversion.

The shape of the coiled fiber obtained as the first step for forming the corrugated 2 or zigzag fiber shown in FIG. 9 constituting the stent of the present invention is as follows. In a state wound in a mold as shown in (1), the treatment is performed at a temperature not lower than the glass transition point and not higher than the melting point of the biodegradable and absorbable polymer material. Preferred temperature conditions are 5 ° C. or higher from the glass transition point, more preferably 1 ° C.
When performed at 0 ° C. or higher, good shaping can be realized. In the second step, a wavy 2 or zigzag molded product is formed by being sandwiched and compressed by the plate-shaped jigs 6 and 7. Also in this shaping, good shaping can be realized by performing at 5 ° C. or more, more preferably at 10 ° C. or more from the glass transition point. This temperature may be the same as the temperature in the first stage. Preferably they are the same or more. Next, as shown in FIG. 11, a corrugated 2 or zigzag fiber is wound into a tube as a third step, and the temperature condition for shaping into a stent shape is also in the above range, that is, the biodegradable and absorbable polymer. A temperature above the glass transition point and below the melting point of the material is appropriate. This temperature may be the same as the temperature in the first and second stages. Preferably they are the same or more.

In the preferred shape of the present invention, the number of heat treatments can be two times, but it is more preferable to perform three times.

In the shaping, the setting time in each step is arbitrary and may be 1 minute or more, preferably 5 minutes or more.

In the stent of the present invention, in the above-described manufacturing method, the internal strain and the amorphous region caused by the deformation are generated in the wavy 2 or zigzag curved portion or the deformed portion 8 at the apex, and the stent is decomposed when placed in the body. It becomes easier,
It may show brittleness. In addition, such a material is liable to be plastically deformed more than necessary, and may not exhibit elasticity necessary for sufficiently expanding a blood vessel during indwelling.

Therefore, by shaping even these deformed portions under the above-mentioned temperature conditions, it is possible to sufficiently crystallize and enhance the elasticity.

The temperature condition is set to be equal to or higher than the glass transition of the fiber and equal to or lower than the melting point, and further, the heat treatment temperature after the first heat treatment is set to be higher. It can be performed, and the internal distortion of the deformed portion due to the first shaping can be eliminated, so that the shape can be maintained until the balloon is expanded in the indwelling operation.

The curved portion or the apex portion, which is the deformed portion, is plastically deformed by expanding the balloon, and the stent can be expanded to a desired diameter.

On the other hand, the portion which has not been deformed in the shaping operation remains in a state where it is oriented and crystallized by the stretching operation, and exhibits sufficient rigidity.
In addition, the plastically deformed portion does not deteriorate due to fatigue and reduced strength when subjected to several times of deformation such as diameter reduction or expansion.
In shaping the stent into a shape, depending on the heat treatment temperature, the corrugated 2 or zigzag fiber wound in a tubular shape may be softened and deformed by heat and may not be shaped into a desired shape. In such a case, from the outer side of the corrugated 2 or zigzag fiber wound in a cylindrical shape, the material is wound with a sealing material, sheet, paper, or the like which does not thermally deform, the shape is maintained, and heat treatment is performed. It is also possible to do In addition, as shown in FIGS. 12 and 13, in the stent of the present invention in which the wavy or zigzag fibers are wound in a tubular shape, the vertexes of the bent portions may be in contact with each other and joined.

The stent of the present invention is mounted on a balloon, inserted therein, and performs treatment by expanding at a stenosis site. When mounted on a balloon,
The stent has a reduced diameter. When the stent of the present invention is mounted on a balloon, the diameter of the stent may be reduced by covering the stent itself with a sheath or the like.

In the stent of the present invention, an X-ray contrast agent may be coated on the surface of the stent or kneaded inside the fiber in order to make the insertion operation easier. This facilitates the insertion and placement operation under X-ray contrast, as in the case of the metal stent.

In the stent of the present invention, a drug may be coated on the surface of the stent or contained in the fiber in order to suppress thickening and inflammation after the stent is placed. As the drug, an anticancer agent, an anti-inflammatory agent, an antithrombotic agent, an antioxidant and the like can be used. Adreamycin, mitomycin C, cisplatin, taxol, taxotere, etc., or derivatives thereof are selected as anticancer agents, steroidal drugs such as dexamethasone are selected as anti-inflammatory agents, and urokinase, heparin are used as antithrombotic agents. , Aspirin, IIb / IIIa, etc., and as the antioxidant, those exhibiting antioxidant effects such as polyphenols, catechins, and vitamin E are selected.

The method of measuring the storage modulus and the glass transition point in the present invention will be described below. (Storage Elastic Modulus) The storage elastic modulus of the fiber according to the present invention can be determined by using a dynamic viscoelasticity measuring device, DV manufactured by IT Measurement Control Co., Ltd.
Using A-225, the measurement was performed in air under the conditions of a measurement frequency of 10 Hz and a heating rate of 5 ° C./min by a heating method. (Glass transition point) DSC measurement was performed using a differential scanning calorimeter DSC-50 manufactured by Shimadzu Corporation under a nitrogen atmosphere (flow rate: 20 ml / min), heating rate: 10 ° C./min, measurement temperature range: room temperature to The measurement was performed at 240 ° C. An empty pan was used as a reference sample.

[0033]

EXAMPLES Examples of the present invention will be described below in more detail.

Example 1 Poly-L-lactic acid having a weight average molecular weight of 280,000 was melt-spun at a molding temperature of 200 ° C.
A fiber of 00 μm was obtained. The obtained fiber was drawn 6 times at 90 ° C. to obtain a fiber having φ160 μm and storage elastic modulus of 8.6 GPa. The Tg of the fiber was about 60 ° C. This fiber was tightly wound in a coil shape around a perfect circular cored bar of φ0.5 mm. The coiled fiber was sandwiched between two glass plates and shaped into a wave at 100 ° C. Subsequently, the obtained wavy fiber was wound around a 1.85 mm φ perfect circular core metal so as not to lose the wavy shape, and shaped into a stent at 110 ° C. to obtain a stent. The diameter of this stent could be easily reduced by compression from the outer periphery, and the diameter could be easily expanded by a balloon catheter.

Example 2 Poly-L-lactic acid having a weight average molecular weight of 280,000 was melt-spun at a molding temperature of 210 ° C.
A fiber of 00 μm was obtained. The obtained fiber was stretched 5 times at 90 ° C. to obtain a fiber having a diameter of 180 μm and a storage modulus of 7.5 GPa. The Tg of the fiber was about 60 ° C. This fiber is wound in a coil shape around a perfect circular cored bar of φ0.9 mm.
The first stage shaping was performed at 0 ° C. The coiled fiber was sandwiched between two glass plates and shaped into a wave at 90 ° C. Next, the obtained wavy fibers were sized at φ1.65.
The corrugated core was wound so as not to lose its wavy shape, and shaped into a stent at 90 ° C. to obtain a stent. The diameter of this stent could be easily reduced by compression from the outer periphery, and the diameter could be easily expanded by a balloon catheter.

As described above, the diameter and pitch of the coiled fiber are more stabilized by applying heat treatment when the cored metal is wound in a coil shape, and the shape can be easily formed in the next step.

Example 3 Poly L-lactic acid having a weight average molecular weight of 280,000 was melt-spun at a molding temperature of 210 ° C.
A fiber of 00 μm was obtained. The obtained fiber was stretched 4 times at 80 ° C. to obtain a fiber having a diameter of 200 μm and a storage modulus of 6.4 GPa. The Tg of the fiber was about 60 ° C. This fiber is wound in a coil shape around a perfect circular core bar of φ0.7 mm.
The first stage shaping was performed at 0 ° C. The coiled fiber was sandwiched between two glass plates and corrugated at 110 ° C. Next, the obtained wavy fiber was φ1.6.
It was wound around a 5 mm perfect circular cored bar without breaking the wavy shape, and shaped into a stent at 110 ° C. to obtain a stent. The diameter of this stent could be easily reduced by compression from the outer periphery, and the diameter could be easily expanded by a balloon catheter.

Example 4 Poly-L-lactic acid having a weight average molecular weight of 280,000 was melt-spun at a molding temperature of 200 ° C.
A fiber of 00 μm was obtained. The obtained fiber was drawn 6 times at 90 ° C. to obtain a fiber having φ160 μm and storage elastic modulus of 8.6 GPa. The Tg of the fiber was about 60 ° C. This fiber is wound in a coil shape around a perfect circular cored bar of φ0.7 mm.
The first stage shaping was performed at 0 ° C. The coiled fiber was sandwiched between two glass plates and shaped into a wave at 100 ° C. Then, the obtained wavy fiber was φ1.8.
It was wound around a 5 mm perfect circular cored bar without breaking the wavy shape, and shaped into a stent at 110 ° C. to obtain a stent. The diameter of this stent could be easily reduced by compression from the outer periphery, and the diameter could be easily expanded by a balloon catheter.

Example 5 The stents described in Examples 1 to 4 were mounted on a balloon and inserted into the rabbit external carotid artery.
The balloon was inflated to expand the stent to the vessel diameter.
Thereafter, the balloon was deflated and removed, and the stent was placed. Necropsy was performed two and four weeks later. After systemic perfusion with a heparinized diet, blood vessels were fixed with a 10% neutral buffered formalin solution. After sufficient fixation, target vessels were excised. The blood vessel in which the stent was placed was embedded in paraffin by a predetermined method to prepare a pathological specimen. Pathological specimen is HE
The cells were stained and observed with an optical microscope. As a result, the inflammatory reaction and hypertrophy were slight, and it was confirmed that the stent of the present invention was excellent in biocompatibility.

[0040]

According to the above-described manufacturing method, it is possible to easily and inexpensively manufacture a stent made of fibers of a biodegradable and absorbable polymer material, and the stent is formed into a shape by expansion with a balloon. It can be expected to have a therapeutic effect of maintaining and preventing stenosis in the blood vessel, and further, being absorbed in the blood vessel and leaving no indwelling object.

[Brief description of the drawings]

FIG. 1 is a view showing an example of a projection view from a lateral direction of a stent of the present invention.

FIG. 2 is a diagram showing an example of a perfect circular cross section of a rod-shaped mold for producing coiled fibers.

FIG. 3 is a diagram showing an example of an elliptical cross section of a rod-shaped mold for producing a coil-shaped fiber.

FIG. 4 is a view showing a state in which fibers for producing the stent of the present invention are densely wound around a rod-shaped mold.

FIG. 5 is a view showing a state in which fibers for producing the stent of the present invention are wound around a rod-shaped mold at an appropriate pitch.

FIG. 6 is a view showing a fiber wound in a coil shape or a fiber in a state in which a densely wound fiber is stretched.

FIG. 7 is a conceptual diagram illustrating a process of compressing a coiled fiber.

FIG. 8 is a conceptual diagram illustrating a state after a coiled fiber is compressed.

FIG. 9 is a diagram showing a wavy fiber formed by compression.

FIG. 10 is a diagram illustrating an example of a mold for shaping into a stent shape.

FIG. 11 is a conceptual diagram showing a state in which a fiber shaped like a wave is wound around the mold of FIG. 10 and shaped into a stent.

FIG. 12 is a diagram illustrating a portion where vertices of a wavy fiber are grounded.

FIG. 13 is a diagram illustrating a portion where wavy fibers are alternately arranged and grounded.

[Explanation of symbols]

 1. 1. Stent body 2. Wavy shaped fibers 3. coiled fibers 4. Wavy shaped fiber sides 5. Part where the wavy fibers are grounded 6. compression jig Compression jig 8. Deformation part

Claims (8)

[Claims] In a stent to be placed in a vessel of a living body, the stent body has a wavy shape formed by winding a fiber folded in a wavy shape or a zigzag shape into a tube, sandwiching the fiber in a plate-shaped jig and compressing the fiber. Alternatively, a stent in which a zigzag molded article is formed, wherein at least two heat treatments are performed in the stent forming step, and the heat treatment is performed at a temperature equal to or higher than the glass transition of the fiber and equal to or lower than the melting point. And a method for producing the stent, wherein the temperature of the subsequent heat treatment is set higher than that. 2. The fiber according to claim 1, wherein the fiber folded in a wavy or zigzag shape is formed by compressing a fiber wound in a coil shape by sandwiching the fiber in a plate-shaped jig. A stent and a method for manufacturing the same. 3. The stent according to claim 2, wherein the cross-sectional shape of the coil-shaped fiber is formed by winding it around a mold having a perfect circle or an ellipse. 4. The stent according to claim 2, wherein the coil-shaped fiber is formed by being closely wound around a mold having a perfect circular or elliptical cross section, and then stretched. Its manufacturing method. 5. The stent according to claim 1, wherein the fiber is a biodegradable and absorbable polymer material. 6. The biodegradable and absorbable polymer material is polylactic acid, polyglycolic acid, polyhydroxybutyric acid, poly (ε
6. The stent according to claim 5, wherein the stent is selected from (caprolactone) or a copolymer thereof. 7. The stent according to claim 1, wherein at least a part of the stent is coated or contained with a drug. 8. The method according to claim 1, wherein the method for expanding the stent is a balloon expansion type.
And a method for producing the same.