JP2002200175A - Biological duct stent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a biological duct stent whose reconstriction rate is low. SOLUTION: The biological duct stent is made of a tube made of a bioabsorbable material, having a plurality of openings on the wall.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biological conduit stent which is useful as a biological conduit expander for expanding a stenotic biological conduit, a cover for covering a biological conduit obstruction such as an aneurysm, and the like. The term biological duct as used herein refers to a tubular tissue in a living body,
Specifically, it refers to blood vessels, trachea, digestive tract, ureter, urethra, fallopian tube, bile duct, and the like.

[0002]

2. Description of the Related Art Conventionally, as a method of dilating a stenotic blood vessel, particularly a living vessel of a coronary artery, a dilatation method using a balloon catheter, cutting of a stenosis site by a rotator or DCA (directional coronary atherectomy) are known. Methods, methods such as metal stent expansion and retention methods have been developed and used in actual surgical settings. Of these methods, the stenosis site is often expanded using a plurality of means. At present, a widely used method is to debulk a calcified portion using a rotator or DCA when the stenotic portion of the artery is calcified, and then expand the stenotic portion using a balloon catheter. When the stenosis is not calcified, the stenosis site is often expanded with a balloon catheter without using a rotatable or DCA. The disadvantage of balloon catheters is that there is always the danger of acute or subacute thrombotic vaso-occlusion when expanding the balloon, forcing the blood vessel wall to open and cracking and damaging it. That is. In addition, restenosis of a stenosis site within 6 months frequently occurs at about 50%. In particular, the former thrombotic occlusion is of high risk because it occurs suddenly after surgery.

[0003] A metallic stent has been devised to avoid such acute or subacute thrombotic vascular occlusion. This metallic stent suppresses flaps and plaques from the blood vessel lumen due to vascular wall cracks during balloon expansion, and thus contributes to greatly reducing the acute thrombotic occlusion rate. Conventionally, heparin, an anticoagulant, has been administered as a post-treatment to prevent thrombus formation after stent placement. The incidence of occlusive obstruction fell to less than 1%. It is said that the endothelial layer covers the stent wall in the blood vessel after about 7 to 21 days after stent placement. Thus, the role of the stent is substantially reduced at this point. In addition, for the restenosis within 6 months, the use of a metal stent reduces the incidence of restenosis compared to using a balloon alone.
Although it has been clarified by trial tests such as STRESS STUDY and the like, since restenosis still occurs at 10% or more, it is important to further reduce the restenosis rate.

[0004] Metal stents are inflexible, tend to apply physical stress to living body ducts such as blood vessels, and cause inflammation of the blood vessel wall and excessive intimal thickening which may be considered as causes of restenosis. There is a problem that the foreign matter remains permanently in the living body. In order to solve the problem of such a metal stent, use of a resin stent has been studied. For example, JP-A-3-205059, JP-A-5-103830 and the like can be mentioned. These patents all use bioabsorbable materials and are disclosed in
No. 59 discloses a single fiber produced and knitted. Japanese Patent Publication No. 5-509008 has not only fibers but also a porous material or pore wound in a cylindrical shape. Japanese Patent Application Laid-Open No. 6-218063 describes a stent made of a bioabsorbable material and containing a multi-layer laminate film containing a drug. JP-A-8-24346 describes a stent made of a reinforced film with biodegradable or bioabsorbable fibers sandwiched inside to increase the strength. Further, Japanese Patent Application Publication No. 10-503663 describes a sleeve or liner made of collagen used in combination with a stent. The earlier patents on metal stents that have been published are the initial objectives,
It is thought to be effective for acute thrombotic coronary artery occlusion tests, but its effect on in-stent restenosis is completely unknown. To achieve the initial purpose of the stent, hold down the flaps caused by PTCA,
It is sufficient for the stent to be stiff enough to withstand the contraction forces of the blood vessels, no further stiffness is required. Conversely, if the hardness is too strong, and if it stays in the blood vessel for a long time like metal, there is no undeniable possibility that the blood vessel may be damaged due to a difference in compliance with the blood vessel. Particularly, in the case of in-stent restenosis, it is not easy to repair a metal stent.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a living body stent having a low restenosis rate.

[0006]

SUMMARY OF THE INVENTION The present invention relates to a biological conduit stent comprising a tube made of a bioabsorbable material and having a plurality of openings on a wall surface.

[0007]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The use of a bioabsorbable material for the base of a biological conduit stent has many advantages over a biological conduit stent made of metal. In particular, regarding in-stent restenosis, which is a problem with metal stents, since bioabsorbable stents are absorbed into the living body, it is possible to re-stent even if restenosis occurs in the installation part Becomes Although it is thought that it is not necessary to place the stent in the stenotic area for more than 6 months for the purpose of stent placement, the bioabsorbable material has a decomposition period of about 3 months like polyglycolic acid and a few months like polylactic acid. Some require years, and if these materials are selected, it is possible to select a material suitable for the required decomposition period according to the application. Also, even with the same material,
It is also possible to shorten the decomposition period by irradiating radiation, for example, γ-rays, and to irradiate polyglycolic acid with γ-rays, the intensity half-life can be reduced to within one week. In addition, additives that induce water at the time of fiber production are added, and the degree of crystallinity and decomposability depending on the crystal structure,
It is possible to control the bioabsorption period. Further, since the hardness of these bioabsorbable stents is smaller than that of metal, the mechanical difference from the blood vessel is small, and the resistance to pulsation of the blood vessel is small.

[0008] Looking at the design of a metal stent,
It can be broadly divided into slot tube type and coil type. Many patents for stents using bioabsorbable fibers have been filed, but these are coil types utilizing the characteristics of fibers, and it is difficult to produce slot tube types from fibers. In a cutting method such as machining (cutting or the like) from a tube and laser cutting in the present invention, both a slot tube type and a coil type can be manufactured.

The advantage of forming an opening penetrating the wall of the tube by the cutting method has the following advantages. (I) Compared to a stent made of a knitted fabric made of fiber, (i) the stent can be made thinner without knots or overlapping at the knot portion. (ii) Openings of various shapes can be formed, (iii) plastic deformation upon expansion is superior to a fiber stent, (iv) by stretching the tubular body to molecular orientation, And the like, which can reduce damage at the time of deformation. In addition, the cutting method has advantages such as lower cost, less influence of heat and less change in physical properties than laser processing.

The opening formed in the tube wall is shown in FIG.
As shown in (a), a corner portion (B portion) may be provided, but when the wall surface 3 around the opening 2 is pulled in the direction of the arrow, a negative stress distribution ( When a tensile stress is applied and an overload is applied to the corner portion (B portion), there is a possibility that the corner portion (B portion) is broken (FIG. 5B). Similarly, when the wall surface 3 around the opening 2 is pulled in the direction of the arrow, a positive stress distribution (compression stress) is applied to the joint (A) as shown in FIG. By forming the notch in the joint (A), the compressive stress in the joint (A) can be reduced. FIG. 6 is a schematic diagram in which a bulged portion 4 with an R added to a corner portion (B portion) is formed and a notch 5 is formed in a joint portion (A portion). For example, FIG. 1 shows a biological channel stent 1 of the present invention having a slit-shaped opening 2 on a wall surface 3.
The stent 1 has no corners, and four bulges are formed around one opening 2. Also,
FIG. 7 exemplifies a partial view of the living body stent in which the cutout 5 is formed together with the bulging portion 4. In addition, it is not always necessary to form the bulging portion, but it depends on the shape of the opening, but preferably at least one, more preferably at least two, particularly preferably at least four per opening. . Also, the notch is not necessarily formed, but preferably depends on the number of joints around the opening, but is preferably formed at least one, and more preferably two.

In a stent made of fiber, the crystal orientation is along the fiber axis. In the present invention, a tube is produced by, for example, drawing an extruder into water to produce an undrawn tube. By stretching the unstretched tube along the axis, oriented crystallization can be performed in the tube axis direction. The stretching ratio of the tube is 2 to 15
About 2 times, preferably about 2 to 6 times. In addition, by rotating the tube at the time of extrusion and performing heat treatment, or by arbitrarily rotating the tube oriented in the tube axis direction above the glass transition temperature, the crystal axis direction is at a predetermined angle with respect to the tube axis direction. Can be set to As the predetermined angle, about 10 to 80 °,
Preferably it is about 45 °. Further, it is also possible to produce a non-oriented tube by, for example, an injection molding method,
These methods make it possible to arbitrarily set an orientation crystal tube and an orientation angle thereof from non-orientation. Orientation in the tube axis direction in this way, optionally crystallinity,
The degree of orientation can not be set with a stent made of fiber, and it can be oriented and crystallized at an arbitrary angle with respect to the tube axis direction only with a stent made of a thermoplastic tube It is what becomes. In particular, poly-L-lactic acid has a stent in which the orientation angle is inclined from the tube axis direction, and exerts a piezo effect by stress from the biological channel after insertion of the biological channel,
In particular, it has the effect of promoting the proliferation of vascular endothelial cells.

A non-oriented tube can be produced by an injection molding method, and the molecular chain can be oriented in the circumferential direction by expanding the tube at a temperature equal to or higher than the glass transition temperature.
These tubes are heat set at the expanded diameter, then reduced in diameter, mounted on a balloon catheter, and transferred to the affected area.
A method of expanding and deploying with a balloon is exemplified. In this method, the opening may be formed by cutting the tube into a predetermined design before the heat setting, or may be formed by cutting the tube after the heat setting. Further, it is also possible to heat-set with a reduced diameter size and use it as a stent by the above-mentioned method. Also in this case, cutting out from the tube may be performed before or after heat setting. It is also possible to heat set the stent by performing stenting with a reduced diameter without heat setting and heating the liquid in the balloon or the balloon itself when expanding the balloon. Can cause problems.

The stent according to the present invention is characterized by being made of a bioabsorbable material. The ideal decomposition period varies depending on the type of the biological duct in the body such as the coronary arteries, arteries, and ureters. However, in this patent, the decomposition period is controlled not only by the material but also by the type of multilayer film and film. Control by thickness and control by foaming are possible.

As the bioabsorbable material, glycolic acid,
L-lactic acid, D-lactic acid, D, L-lactic acid, p-dioxanone, ε-caprolactone, ethylene glycol, a homopolymer having monomer units of trimethylene carbonate or a copolymer of two or more monomers, collagen, Examples include gelatin, chitin, chitosan, hyaluronic acid, and alginic acid, and preferably polyglycolic acid (PG
A) and poly-L-lactic acid (PLLA) are exemplified, and more preferably poly-L-lactic acid (PLLA) is exemplified.

The average molecular weight of the bioabsorbable polymer constituting the bioabsorbable material is 10,000 to 800,000.
It is preferably about 0, preferably about 100,000 to 400,000.

The outside diameter of the living body stent of the present invention is about 1 mm to 15 mm when the balloon is attached, and the outside diameter is about 2.5 mm to 40 mm when expanded. Appropriate stent diameter and length are determined by the type and diameter of the biological conduit using the stent. For example, in the case of a stent for coronary artery, the inner diameter when expanded is 2.5 mm to 4.0 mm and the length is 1 mm.
It is preferable that the inner diameter at the time of expansion is 5 mm to 40 mm, the inner diameter at the time of expansion is 11 mm for a urethral stent, and 4 cm to 10 cm, and the inner diameter at the time of expansion is 25 mm to 30 mm for an aortic stent.

The stent of the present invention can be manufactured so as to have the outer diameter when the balloon is mounted, and to have the outer diameter when the balloon is expanded (the diameter of the blood vessel to which the stent is mounted). You can also.

In one preferred embodiment, the outer diameter of the tube constituting the stent is made equal to the outer diameter at the time of expansion, and an opening is formed in the tube, preferably by a cutting method. In order to make the diameter suitable for setting in a balloon, it can be inserted into a tube having an appropriate inner diameter and heat-set to reduce the diameter. In this case, the outer diameter of the stent is 1.5 to 40 mm.
The outer diameter after diameter reduction is about 1.0 to 35 mm.

In another preferred embodiment, the outer diameter of the tube constituting the stent is adjusted to the diameter of the balloon, and an opening is formed in the tube, preferably by a cutting method. In such a stent, when the balloon is expanded, the shape of the opening extends in the radial direction of the stent, so that the stent can be expanded to the diameter of the biological channel in which the stent is mounted (see FIGS. 1 and 4). The shape of the opening when the diameter of the stent is expanded in this way is a slit shape, a circle,
An arbitrary shape such as an ellipse, a rhombus, a rectangle, a square, a scale, and the like can be mentioned. Conversely, when expanded, a cut is made in the wall surface in advance to have such a shape, and an opening is formed. The diameter of the stent before expansion is slightly larger than the diameter of the balloon, and can be closely attached to the balloon by caulking when attached to the balloon.

As the radiopaque material, barium sulfate,
Gold and platinum are exemplified, and barium sulfate can be coated on the surface of the stent or kneaded inside. Also, gold and platinum can be attached as chips to appropriate portions of the stent.

In the case where the stent of the present invention is used as a covering device for a biological duct obstruction such as an aneurysm, it is preferable to wrap a film or cloth around the outside, inside, or both sides of the tubular biological duct stent. Examples of the material of the film or cloth include non-biodegradable polymers, and specific examples thereof include polyolefins such as polyethylene and polypropylene, polystyrene, polyester, polyurethane, polyamide, and fluorine-based resins.

The film or cloth is preferably joined or fixed to a tube made of a bioabsorbable material constituting the stent. Joining or fixing may be performed with a thread, a method of bonding with an adhesive, no fusion,
It can be performed by a method of welding with a solvent or the like.

The tube constituting the stent may have a multilayer structure or a single-layer structure. Examples of the tube having a multilayer structure include, for example, a three-layer structure in which an inner layer containing a bioabsorbable reinforcing fiber is sandwiched by an outer layer made of a bioabsorbable material.

Various chemicals can be contained on the surface or inside of the tube by coating, dipping, impregnating, spraying or the like. Examples of such agents include anticoagulants or / and antiplatelet agents such as heparin and its analogs, cell growth factors and the like.

The surface of the tube, cloth or film can be subjected to a hydrophilization treatment by corona discharge, plasma treatment, radiation treatment, ultraviolet treatment, ozone treatment or electron beam treatment.

The tube may be a foam of a bioabsorbable material.

An example of a method for processing a cutting stent is described below. (a) Cut a tube processed to an outer diameter (φ1.0-40.0mm) and thickness (0.01-1.5mm) to a length of 15-50mm; (b) A polymer rod or metal rod that fits the inner diameter of the tube Prepare a resin-coated material, insert the tube into the rod, and fix both sides of the tube with dedicated pinches; (c) The polymer rod with the tube set on the machining center work part (D) Using a φ0.2 to 6.0 mm end mill, axially insert grooves of 1 to 30 mm length into the tube at a constant pitch. The tool axis of the end mill is moved only on the tube axis. (E) The polymer rod is rotated by a special jig, and another groove is formed at a position shifted by rotation. (f) Groove processing is completed on the entire circumference, and a cut that becomes the end face of the product is made by rotating the polymer rod (tube) with a special jig by rotating the polymer rod (tube) through the end mill through the tube and making one round.

The laser used for laser cutting includes excimer laser, semiconductor laser, dye laser, gas laser (carbon dioxide laser, argon ion laser, helium-neon laser, etc.), solid laser (Nd: YAG laser, Ti: Sapphire laser, etc.) and free electron laser.

FIG. 1 shows a slit-shaped opening 2 by cutting.
An example of the manufactured biological conduit stent 1 will be described.
Four bulges 4 are formed in the tube wall 3 per opening to relieve tensile stress during stent expansion. FIG. 4 is a partially enlarged view showing a state where the living body stent of FIG. 1 is mounted on a balloon and expanded. FIG. 6 shows a partial view in which two notches 5 are formed in the wall surface 3 per one opening 2.

As a feature of the present invention, it is possible to change the thickness of a portion, which is not possible with a fiber stent. By designing a part to be cut at the time of expansion and a part to be plastically deformed, it is possible to increase or decrease the apparent elasticity at the time of expansion. Moreover, the biological channel stent manufactured by the method of the present patent can improve the trekkability along the biological channel by these designing.

[0031]

According to the present invention, a living body stent having a low restenosis rate can be obtained.

[0032]

The present invention will be described in more detail with reference to the following examples. Example 1 Using a melt extruder having a screw diameter of 30 mm using poly-L-lactic acid having an average molecular weight of 200,000 as a raw material,
The tube was extruded into the air with a mandrel 14 mm and air-cooled at the take-up speed shown in Table 1 to produce a tube. Table 1 shows the outer diameter and inner diameter of the manufactured tube. Example 2 No. 2 in Table 1 3 (inner diameter 3.14mm, outer diameter 3.65m
m) is cut to a length of 1.5 cm. FIG. 1 shows a vascular stent obtained by placing this tube on a stainless steel rod (3.14 mm after coating) coated with a water-soluble polymer and machine-cut using a machining center (FIG. 2). Example 3 The plastic shafts of 0.5 mm increments shown in Table 2 are passed through the vascular stent of Example 2 at room temperature in order of decreasing diameter. Pass through a bar of one size, leave for 15 seconds and pull out and measure its inner diameter. Table 3 shows the inner diameter after passing the insertion shaft diameter up to 8 mm. FIG. 3 shows Table 3 as the inner diameter of the vascular stent after the expansion operation with respect to the insertion shaft diameter.
It is. As is clear from FIG. 3, the insertion shaft diameter is 5.5 mm.
From the above, it can be seen that the expansion is performed beyond the elastic deformation.

That is, these results show that the plastic deformation upon expansion is superior to that of the fiber stent. Specifically, the plastic deformation is almost the same as the insertion shaft diameter of up to 5.0 mm. The diameter of the stent naturally reduces to the diameter of, but when the insertion shaft diameter is expanded to 5.5 mm or more, the natural diameter decreases to 1.6.
mm, and there is no spontaneous diameter reduction beyond that. In the present invention, such a property is defined as a function deformed beyond elastic deformation. The above results indicate that the stent can be placed in accordance with the intended diameter of the conduit by expanding the balloon with a balloon in consideration of the natural diameter reduction of 1.6 mm. Example 4 6 was placed on the balloon portion of a PTCA balloon catheter prepared according to Example 2 and an expansion test was performed using cadaver pig lung blood vessels. The balloon portion was inserted until the inner diameter of the blood vessel was 3 mm, and the stent was expanded by applying pressure to 8 kg / cm ² with an inflator. After maintaining this state for 30 seconds, the inside of the balloon was depressurized, and the balloon was removed from the stent to place the stent. The stent portion was cut out and observed, and as a result, the stent was sufficiently expanded.

[0034]

[Table 1]

[0035]

[Table 2]

[0036]

[Table 3]

[Brief description of the drawings]

FIG. 1 shows a front view of a biological conduit stent of the present invention having a slit-shaped opening.

FIG. 2 shows a configuration diagram of a cutting system.

FIG. 3 is a graph showing the results of a stent expansion test.

FIG. 4 is a view showing a state of the stent of FIG. 1 at the time of expansion.

FIG. 5 is an explanatory diagram showing what kind of stress is applied to a corner (B) and a joint (A) when a stent is expanded.

FIG. 6 is a schematic diagram showing a bulged portion and a notch on a stent wall surface.

FIG. 7 is a diagram showing a notch in a wall surface of a stent.

[Description of Signs] 1 stent 2 opening 3 wall surface 4 bulging portion 5 notch

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Shojiro Matsuda 46 Aomachi Natsuga-shi, Ayabe City, Kyoto Prefecture Gunze Co., Ltd. Medical Materials Center, Research and Development Department (72) Inventor Yoshito Raft, Goga Shohiro, Uji City, Kyoto Prefecture 2-182 Okaya F term (reference) 4C167 AA44 AA49 AA55 BB31 CC09 DD01 GG12 GG34 GG35 GG43 HH30

Claims (21)

[Claims] 1. A biological conduit stent comprising a tube made of a bioabsorbable material and having a plurality of openings on a wall surface. 2. The biological conduit according to claim 1, wherein at least one bulge portion for reinforcing tensile stress during expansion and at least one notch for absorbing compressive stress during expansion are formed on a wall surface. Stent. 3. The stent according to claim 1, wherein the opening is formed by laser cutting, punching, machining, or the like. 4. The living body stent according to claim 1, wherein the stent is made of a stretched material. 5. The biological conduit stent according to claim 1, wherein the stent is heat-set at a temperature higher than the glass transition point of the bioabsorbable material. 6. The method according to claim 1, wherein the diameter is reduced at a temperature higher than the glass transition point of the bioabsorbable material, and then heat set at the temperature at the time of diameter reduction or at a temperature higher than the temperature. 2. The biological channel stent according to item 1. 7. The biological conduit stent according to claim 1, wherein at least a part of the tube used is deformed beyond elastic deformation when expanded by the balloon. 8. The bioabsorbable material is glycolic acid, L-lactic acid, D-lactic acid, D, L-lactic acid, p-dioxanone, ε-lactic acid.
Homopolymer having caprolactone, ethylene glycol and trimethylene carbonate as monomer units or 2
The biological duct stent according to any one of claims 1 to 7, which is a copolymer comprising at least one kind of monomer, collagen, gelatin, chitin, chitosan, hyaluronic acid, alginic acid, or the like. 9. The stent according to claim 8, wherein the surface of the bioabsorbable material is subjected to a hydrophilic treatment by plasma discharge, electron beam treatment, corona discharge, ultraviolet irradiation, ozone treatment or the like. 10. A method in which at least a part of a tube used is coated with a natural polymer such as collagen, gelatin, chitin, chitosan, hyaluronic acid, or alginic acid, or a synthetic polymer such as polyvinyl alcohol or polyethylene glycol. The living body stent according to any one of claims 1 to 9, wherein 11. The biological duct stent according to claim 1, wherein the tube axis direction of the biological duct stent and the crystal orientation direction of the bioabsorbable material form different angles. 12. A radiopaque material (barium sulfate, gold, platinum, or the like) or a drug such as an antiplatelet agent, an anticoagulant, or a smooth muscle cell proliferation inhibitor, on at least a part of or the surface of the bioabsorbable material. 2. The method according to claim 1, wherein
The biological conduit stent according to any one of claims 1 to 7. 13. The stent according to claim 1, wherein the bioabsorbable polymer constituting the bioabsorbable material has an average molecular weight of 10,000 to 800,000. 14. The living body according to any one of 1 to 13, wherein the outer diameter is 1 mm to 15 mm when the balloon is mounted (when the diameter is reduced, the outer diameter is reduced when the balloon is mounted) and 2.5 mm to 40 mm when the balloon is expanded. Conduit stent. 15. A living body stent in which a film or cloth is wound around the outside, inside or both sides of the stent according to any one of claims 1 to 14. 16. The stent according to claim 15, wherein the film or cloth is joined or fixed to a tube constituting the stent. 17. A living body stent obtained by wrapping a film or cloth around the outside, inside or both sides of the stent according to any one of claims 1 to 16, and ligating the cloth or film on both sides with a thread or the like. . 18. The tube according to claim 1, wherein the tube has a multilayer structure.
18. The biological duct stent according to any one of 17. 19. The stent according to claim 18, wherein the inner layer or the outer layer of the tube contains reinforcing fibers. 20. The tube, cloth or film surface is subjected to a hydrophilic treatment.
10. The biological duct stent according to any one of 9 above. 21. The stent of claim 1, wherein the tube is a foam of a bioabsorbable material.