JPH11299900A - Stent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prevent reclosure and reconstriction and to improve the performance to prevent recoiling of a blood vessel wall, etc., by providing at least part of a stent with a portion embeddable into a vascular cavity wall. SOLUTION: The stent is provided with the embeddable portion 5a and the embeddable portion 5a is embedded into the wall of the vascular cavity wall 2 of the blood vessel, etc. Another portion 5b of the stent is exposed into the vascular cavity inside 3. The portion 5b may not be exposed in the vascular cavity inside 3 and may be flush with the inside surface of the vascular cavity wall 2 when the embedded portion 5a is embedded. In such a case, >=50% of the total stent volume is embedded into the vascular cavity wall 2 of the blood vessel, etc. to decrease the portion exposed from the vascular cavity wall 2. The embedded portion 5a is formed sharply so that the stent may be smoothly inserted to the vascular cavity wall 2 at the time of dilation by a balloon, etc. As a result, the insertion is made smooth and the recoiling of the blood vessel wall, etc., is prevented. An initial dilation effect and mechanical strength may be improved.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a stent (sten).
More particularly, the present invention relates to a stent for opening a lumen including a blood vessel narrowed or obstructed by a lesion. The stent of the present invention can be used for percutaneous coronary angioplasty (PTC).
A) It can be used particularly suitably for interventional treatment for acute coronary occlusion and restenosis after. Further, the stent of the present invention can be used for a treatment method for maintaining a lumen that has been occluded or narrowed due to cancer or the like.

[0002]

2. Description of the Related Art The application site and application method of the stent of the present invention are not particularly limited, but for convenience of explanation, a typical use method of a recent stent is "interventional treatment".
The conventional technology will be described with reference to an example.

[0003] In recent years, many stents have been clinically placed in the coronary artery as interventional treatments for acute coronary occlusion and restenosis after percutaneous coronary angioplasty (PTCA). Placement of this stent in the coronary artery has been shown to have a pronounced initial dilation effect, and has also been shown to be somewhat effective in preventing acute coronary occlusion and restenosis.

Conventionally, the structures of stents that have been developed are roughly classified into slotted tube stents having a tubular structure and coil stents made of a single wire. Can be.

The oldest and most widely used slotted tube stent in clinical practice is the Palmaz-Schatz stent. This Pal
The maz-Schatz stent consists of a stainless steel tube with a number of slits, and when the stent is expanded by a balloon (constituting a balloon catheter or the like), the slit of the stainless steel tube is diamond-shaped. And thereby exerts the function of expanding the lumen.

A Multilink stent having a tubular structure in which a plurality of links are connected also has a structure which is similarly expanded by a balloon.

On the other hand, examples of a coil stent formed of one wire include a Wiktor stent and a Cordis stent. These stents are classified into a type that is expanded by the balloon and a self-expandable type.

Most of the materials of the above-mentioned stents are metals. Among them, stainless steel or tantalum is mainly used from the viewpoints of biocompatibility, mechanical properties, workability and the like.

As described above, various stents having different structures and / or materials have been developed according to the purpose of use, the method of indwelling, and the like. As already mentioned, the greatest benefit of using a stent is in balloon angioplasty,
In the absence of a stent, most of the cases show acute recoil in the blood vessel after balloon dilatation, whereas the use of a stent significantly reduces recoil, ie, the use of a balloon / stent. A good initial dilation effect of blood vessels is obtained.

[0010] On the other hand, common problems in the use of various stents are occlusion due to thrombus formation at the early stage of the stent placement and reocclusion or restenosis at the later stage of the stent placement.

It is believed that metal (stent material), which is a foreign substance to the living body, promotes thrombus formation. The reocclusion or restenosis seen several weeks to several months after the stent placement is considered to be due to excessive proliferation of neovascular intima at the stent placement site. Although there are several theories about the mechanism of neointimal hyperproliferation, the following findings indicate that thrombus formed in the early stage of indwelling induces hyperproliferation of the neointimal membrane. Theories are believed to be most likely.

That is, when a stent is placed in a dog coronary artery, one week later, a thrombus is formed around the stent, and three weeks later, the thrombus is replaced by macrophages, and the initial formation of neointima is seen. Eight weeks later, neointimal hyperplasia mainly composed of fibroblasts is observed (Schatz RA e
tal: Circulation 76 , 450, 1987).

[0013] In addition, a stent was placed in the aorta of a hereditary hyperlipidemia (WHHL) rabbit, and then pathological changes in the wall of the aorta were searched over time. Thrombus was observed in the thrombus, macrophage accumulation was observed in the thrombus attachment area around the stent over time, and neointima was formed to cover the stent (Takagi M et al.).
al, Atherosclerosis 10 9, 6, 1994).

On the other hand, through a search of autopsy cases after human coronary artery stenting, the characteristics of subacute thrombotic occlusion after stenting, the neointimal formation process, and the mechanism of restenosis were studied. (Less than 7 days), thrombus adhesion was observed around the stent wire, and accumulation of a small number of macrophages was found in the thrombus. On the 9th and 12th days after the placement of the stent, fibrin thrombus was observed around the stent wire, and the formation of primary neointima mainly composed of macrophages and spindle cells was observed around the stent wire. In the one-month stent placement example, a fibrin thrombus remained around the stent wire, and a neointima composed of smooth muscle cells and macrophages was observed in the thrombus in a worm-eating state. In restenosis cases, remarkable neointimal hyperplasia mainly composed of smooth muscle cells was observed. In cases more than one year after stenting, the luminal surface of the neointima was completely covered by regenerative vascular endothelium (Komatsu R et al, J Am Coll C
ardiol 29 , 312A, 1997).

From the above-mentioned animal experiments and studies on human clinical cases, as a mechanism of reocclusion or restenosis, when a thrombus is formed around a stent wire in the early stage of placement, macrophages accumulate in the thrombus and platelet-derived growth factor ( P
(DGF) and other growth factors to induce smooth muscle cell migration and proliferation, leading to excessive neointimal proliferation. Therefore, suppression of thrombus formation in the early stage of implantation is considered to lead not only to prevention of acute thrombotic occlusion but also to prevention of reocclusion or restenosis in the later stage of implantation (Tatsushi Komatsu et al., Therapeutics 31). , 1063, 19
97).

As described above, the material of the stent is a metal such as stainless steel, and is originally a material that is very easy to form a thrombus. For this purpose, strong anticoagulant or antiplatelet therapy has been used to prevent thrombus formation, but not only with the risk of bleeding of the living body itself, but also until microthrombus formation around the stent wire. It is difficult to stop. In addition, stents placed in the vascular endothelium are believed to induce turbulence in blood flow and form thrombi. In general, when a projection is formed on a smooth surface (for example, an inner wall of a blood vessel), thrombus formation is not seen on the smooth surface, whereas prominent thrombus formation is induced around the projection on the downstream side ( Hiroshi Imachi et al., History of Medicine 78 , 756, 197
1). In addition, thrombus formation increases in proportion to the height and amount of the protrusion (Yoshikawa K. et al., Artificial Organ 4 (Suppl), 107, 197).
Five).

Therefore, in order to suppress the formation of a thrombus of the stent as a protrusion on the blood vessel wall, it is necessary to minimize the amount of metal forming the stent and the height of the protrusion, that is, the thickness of the stent. However, in order to prevent reocclusion or restenosis against vascular recoil, which is the most important function of the stent, a high radialfo
rce or mechanical repulsion is required, i.e., sufficient metal and stent strut thickness or stent wire caliber. On the other hand, according to the findings of the present inventor, it is presumed that in the current stent, this causes thrombus formation, and further causes reocclusion or restenosis often observed in long-term placement.

[0018]

As described above, the metal amount of the stent or the thickness of the stent necessary for preventing recoil of the blood vessel wall and the like and for exhibiting a good initial expansion effect is determined by hemodynamically forming a thrombus. It induces reocclusion or restenosis not only in the acute phase but also in the chronic phase. On the other hand, if the amount of metal forming the stent and the height of the protrusions (that is, the thickness of the stent) are made as small as possible with emphasis on suppressing thrombus formation, the recoil prevention function of the blood vessel wall and the like becomes insufficient,
There has been a strong demand for stents to achieve both.

An object of the present invention is to provide a stent that solves the above-mentioned problems.

Another object of the present invention is to provide a stent that can achieve both a function of preventing recoil of a blood vessel wall and the like and suppression of thrombus formation.

[0021]

Means for Solving the Problems As a result of earnest studies, the present inventors have made it possible to provide a stent with a structure that can be embedded at least partially in a lumen wall such as a blood vessel wall. It was found to be extremely effective in solving the problem.

The stent of the present invention is based on the above findings, and more specifically, is characterized in that at least a part thereof has a portion that can be embedded in the lumen wall.

The basic concept of the present invention having the above-described structure is that a portion which is responsible for mechanical properties for preventing reclosion or restenosis against recoil of a lumen wall such as a blood vessel, which is the most important function of a stent. Is mainly buried in the lumen wall such as a blood vessel wall, and by reducing the portion exposed on the lumen inner wall as much as possible, not only prevention of thrombus formation and the like,
An object of the present invention is to prevent reocclusion or restenosis at the later stage of implantation due to neointimal hyperproliferation.

As described above, in a long-term indwelling example in which reocclusion or restenosis does not occur, the surface of the stent is covered with neovascular endothelium and is in a very stable state. The basic concept of the present invention is to bury at least a part of a stent in a lumen wall of a blood vessel or the like so as to minimize the portion of the stent exposed on the inner surface of the lumen wall, and to cover the stent with a new (vascular) endothelium. To promote and create a stable state. In particular, it is intended to reduce the surface area exposed on the inner wall surface of the lumen and to make it flush with the inner surface of the lumen (to minimize the height of the protruding portion exposed to the inside of the lumen as much as possible). .

[0025]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described more specifically with reference to the drawings as necessary. In the following description, “parts” and “%” representing quantitative ratios are based on weight unless otherwise specified.

(Stent) In the present invention, the term "stent" refers to a structure that is temporarily or semi-permanently placed inside a lumen to maintain the inner diameter of the lumen.
The structure of the stent is not particularly limited as long as it performs such a function.

From the viewpoint of ease of manufacture, the stent of the present invention preferably has a slotted tube stent type structure. An example of such a slotted tube stent type structure is the Palmaz-S, which can be made by slitting a tubular tube.
Examples include a chatz stent and a Multilink stent having a tubular structure in which a plurality of links are connected.

From the viewpoint of placing the stent in the lumen, the stent of the present invention preferably has a “balloon-expandable type” structure that can be expanded by expanding a balloon portion such as a balloon catheter.

(Embeddable Portion) The structure of the portion of the stent of the present invention which can be embedded in the lumen wall can be embedded in the lumen without destroying or rupturing the lumen. Is not particularly limited.

From the viewpoint of the balance between mechanical properties for preventing lumen reocclusion or restenosis and functions for preventing thrombus formation, etc., the volume of the portion of the stent of the present invention that can be embedded in the lumen wall is as follows: It is preferably at least 50%, more preferably at least 80% (especially at least 90%) of the entire stent volume.

(Structure of Stent) Hereinafter, the structure and use of the stent of the present invention will be described with reference to the drawings.

FIG. 1 (an example of a slotted tube stent) and FIG. 2 (an example of a coil stent) are schematic cross-sectional views of a conventional stent installed on the inner surface of a lumen such as a blood vessel.

Referring to FIG. 1, stent strut 1
Are arranged inside the lumen 2 such as a blood vessel. On the other hand,
Referring to FIG. 2, a stent wire 4 is disposed inside a lumen 2 such as a blood vessel. That is, in any of the conventional stents as shown in FIGS. 1 and 2, most of the stent struts 1 or the stent wires 4 are not only exposed on the inner surface of the lumen 3 but also most of them. It protrudes from the inner surface of the lumen. According to the measurement by the present inventors, the metal surface area of the conventional stent is 10 to 20% (based on the total surface area of the inner surface of the lumen of the stent placement part), and the thickness of the stent is 70 to 150 μm. Met.

FIGS. 3 and 4 are schematic sectional views showing examples in which the stent of the present invention is placed in a lumen such as a blood vessel. Referring to FIG. 3, an implantable portion 5a of the stent of the present invention is embedded in the wall of a lumen 2 such as a blood vessel, while a portion 5b of the stent is exposed to the interior 3 of the lumen. doing.

On the other hand, referring to FIG. 4, an implantable portion 6a of the stent of the present invention is embedded in the wall of the lumen 2 such as a blood vessel. In the embodiment of FIG. 4, there is substantially no stent portion exposed to the interior 3 of the lumen 2, and the exposed surface 6b of the stent to the interior 3 is flush (substantially flush with the lumen inner surface). )It has become.

As shown in these figures, in the stent of the present invention, preferably 50% or more (more preferably 80% or more, particularly 90% or more) of the entire stent volume is covered by a luminal wall such as a blood vessel. The portion which is buried in the inside 2 and is exposed on the inner surface of the lumen of the stent is reduced.

The stent of the present invention has a sharp portion (5a in FIG. 3, 6a in FIG. 4) so that it can be embedded in the lumen wall. This embeddable portion is not only smoothly inserted into the lumen wall 2 such as a blood vessel when expanded by a balloon or the like, but also has a mechanical strength for preventing recoil of the blood vessel wall or the like and exhibiting an initial expansion effect. Enhance.

In the stent of the present invention, the depth of the buried portion of the blood vessel or the like in the lumen wall (black portion 5a in FIG. 3 and 6a in FIG. 4) depends on the type and location of the lumen used. Although different, it is preferably 1/10 to 2/3 (more preferably 1/5 to 1/2) of the average thickness of the lumen wall.

(Material) The material of the stent of the present invention is not particularly limited, but is preferably a metal and / or a polymer from the viewpoint of excellent mechanical strength and spreadability. As the metal, stainless steel and tantalum conventionally used for stents can be suitably used.

Further, as a material which satisfies hardness and spreadability which are important properties for the stent of the present invention and which is stable in the lumen wall, platinum, an alloy of platinum and gold, titanium or titanium Alloys and the like can be used.

(Porous Metal) The stent of the present invention can be made of a porous metal. Such a porous metal material can be particularly suitably used for the purpose of causing a stent to carry a physiologically active substance or the like and thereby sustaining release.

(Polymer) In the present invention, a polymer material can also be used as a stent material. That is, in the present invention, the portion embedded in the lumen wall of the stent also contributes effectively to the mechanical repulsion against the recoil of the blood vessel. Also, a polymer material having poor elasticity can be used as the stent material.

As described above, when the mechanical properties similar to those of the metal stent are achieved by the stent made of a polymer material, the volume of the polymer material used for the stent is larger than that of the metal material. there is a possibility. However, in the stent of the present invention, it is possible to bury a main part of a large-capacity polymeric stent in a lumen wall such as a blood vessel so as to reduce a part of the stent exposed in the lumen. Therefore, as described above, even when a polymer is used as a stent material, thrombus formation or restenosis can be suppressed.

The polymer material that can be used for the stent of the present invention is not particularly limited. For example, a polymer having excellent mechanical properties represented by polytetrafluoroethylene, polyethylene, polypropylene, nylon, polyester and the like is preferably used. Can be used.

In the present invention, a biodegradable polymer may be used as a stent material, and the stent may be decomposed or eliminated in vivo as needed. Examples of the polymer material that is metabolically degraded in a living body include biodegradable polyesters represented by polyglycolic acid, polylactic acid, various polylactones, and the like.

(Combination of Materials) As the stent material of the present invention, a metal and a polymer material may be used in combination, if necessary. For example, the stent of the present invention can be produced by arranging the above-mentioned polymer material on the surface of the above-mentioned metal material by coating or the like. In particular, as a polymer material for coating,
The above-mentioned biodegradable polymer material can be suitably used for the purpose of carrying a physiologically active substance and releasing it gradually.

(Physiologically Active Substance) If necessary, the physiologically active substance to be carried on the stent of the present invention to be sustainedly released is not particularly limited, and one or more known physiologically active substances may be appropriately selected or used in combination. It is possible. Such physiologically active substances include, for example, thrombus formation inhibition, thrombolysis,
Substances having various functions such as platelet adhesion / aggregation suppression, infection prevention, anticancer properties, and cell growth suppression are exemplified.

(Preparation Method) The preparation method of the stent of the present invention is not particularly limited, and can be appropriately selected or combined from known stent preparation methods.

For example, when the stent of the present invention is made of a metal material such as stainless steel, for example, as shown in a schematic perspective view of FIG. A method in which a sharp portion (portion that can be buried in the lumen wall) 7 for introduction is cut out, and the surface is polished and smoothed by an electrolytic polishing method or a chemical polishing method can be suitably used.

In FIG. 5, the portion 7 to be buried in the lumen wall is thin and sharp on the outer peripheral side so as to be easily buried in the lumen wall, while the inner peripheral side is a balloon or the like. The wall thickness is designed to be large so as not to damage the
See cross section.)

Such a laser processing method itself is known as a conventional stent processing method (for details of the metal laser processing method, see, for example, the literature, “Micro Processing Technology-Second Edition” edited by the Micro Processing Technology Editing Committee. Edition- ", p. 52 (1988), see Nikkan Kogyo Shimbun).

On the other hand, when the stent material is a polymer material, it can be manufactured in the same manner as in the case of the metal material described above.

Further, the method of coating the surface of the metal stent with various polymer materials is not particularly limited, and a conventionally known coating method can be used. As the known method, for example, a solvent casting method of dissolving a polymer material in a solvent, coating the solution by immersing the stent, and then evaporating the solvent;
A method in which a polymer material powder is adhered to a metal surface by an electrostatic coating method or the like, and then the polymer material is melted to form a coating film.

The method for introducing the above-mentioned physiologically active substance into the stent material of the present invention is not particularly limited, and a conventionally known introduction method can be used. As the known method, when the stent material is a porous metal, the physiologically active substance is dissolved in a solvent, the porous metal is immersed in the solution, and the physiologically active substance is introduced into the pores. A method of evaporating the solvent is suitably used. When the stent material is a polymer material, a method of simultaneously dissolving or dispersing the polymer material and the physiologically active substance in a solvent, and then evaporating the solvent,
A conventionally known method such as a method of eutectic melting the polymer material and the physiologically active substance can be used.

(Method of Use) The method of using the stent of the present invention is not particularly limited. For example, in the present invention, almost the same method as that of a conventional slotted tube stent can be used.For example, the stent is mounted on a balloon of a balloon catheter, inserted to the stent placement site, and the balloon is expanded. Thus, the stent can be expanded and placed in a lumen such as a blood vessel.

Unlike the conventional stent, the stent of the present invention has a portion which can be buried outside (for example, a sharp portion). When the balloon is expanded, the buried portion cuts through the lumen wall and inserts into the wall. You will be buried. Therefore, when using the stent of the present invention, it is preferable to place the stent after sufficient predilation with a balloon at a lesion that has been occluded or stenotic due to thrombus formation or calcification.

In the stent of the present invention, a portion (for example, a sharp portion) that can be buried outside is arranged.
Preferably, the stent is covered with a sheath or the like to protect the normal lumen wall sufficiently so as not to damage the normal lumen wall until the stent is introduced into a lesion.
The method of protecting the normal lumen wall itself with such a sheath is
This is a method that has been used even when a conventional stent is used.

As described above, a feature of the stent of the present invention is that at least a part (preferably, most) of the structure is buried in the lumen wall of a blood vessel or the like and is exposed on the inner surface of the lumen. That is, the part is reduced.

In the case of blood vessels, obstacles protruding into the lumen of blood vessels cause acute occlusion or restenosis due to thrombus formation. In the case of esophagus, etc., they obstruct the smooth passage of food, and in the case of bile ducts, pancreatic ducts, etc. Also hinder the passage of digestive juices. on the other hand,
Diseases for which the stent is to be placed are blood vessels with advanced arteriosclerotic lesions such as calcification, and a method of removing plaque or calcified portion with a razor or a rotating blade when expanding the balloon of PTCA, or using a blade. In general, a method of making an incision in a blood vessel wall with a balloon having a hole is used. Therefore, according to the knowledge of the present inventor, an implantable portion (for example, a sharp portion) of the outer periphery of the stent of the present invention is used.
It is presumed that the damage caused by incising the diseased vessel wall is not substantially significant.

Similarly, stenosis due to esophageal cancer, bile duct cancer, bronchial cancer, or the like, or embedding of the stent of the present invention in the occluded lumen wall is not likely to be a major obstacle.

Furthermore, as can be seen from the clinical findings of a conventional stent placed on the inner surface of a lumen such as a blood vessel, in a long-term placement example, the conventional stent is completely covered by neointima, Is believed to be stabilized by being buried in (eg, Komatsu R et al, JA
m Coll Cardiol 29 , 312A, 1997). Therefore, according to the findings of the present inventor, it is presumed that the stent of the present invention should be buried as much as possible in the lumen wall from the initial stage of placement of the stent, rather contributing to the stabilization of the stent.

[0062]

As described above, according to the present invention, there is provided a stent characterized in that at least a part thereof has a portion which can be embedded in a lumen wall.

Since the stent of the present invention is at least partially (preferably most) buried in the lumen wall of a blood vessel or the like, the portion exposed or projected on the inner surface of the lumen is reduced, and acute Obstruction or restenosis can be effectively prevented.

Further, in the case of the stent of the present invention, the portion of the blood vessel or the like exposed on the inner surface of the lumen is minimized to reduce the volume of the portion of the blood vessel or the like that resists recoil, that is, the volume of the portion buried in the lumen wall. According to the present invention, although it is possible to increase the size of the polymer material, the polymer material is inferior in mechanical properties to metal, but is capable of imparting biodegradability or supporting and / or sustaining release of a physiologically active substance. Can be used as a material for a stent.

[Brief description of the drawings]

FIG. 1 is a schematic cross-sectional view showing an example of an embodiment in which a conventional stent is placed in a lumen.

FIG. 2 is a schematic cross-sectional view showing another example of a mode in which a conventional stent is placed in a lumen.

FIG. 3 is a schematic sectional view showing an embodiment in which the stent of the present invention is placed in a lumen.

FIG. 4 is a schematic cross-sectional view showing another embodiment in which the stent of the present invention is placed in a lumen.

FIG. 5 is a schematic perspective view showing one embodiment (an embodiment having a sharp portion on the outside) of the configuration of the stent of the present invention.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Stent strut, 2 ... Luminal wall, 3 ... Inside the lumen, 4 ... Stent wire, 5a ... Stent embedable part, 5b ... Stent lumen exposed part, 6a ... Stent embedable part, 6b ... Stent Exposure surface in the lumen, 7 ... buried part.

Claims (7)

[Claims] 1. A stent characterized in that at least a part thereof has a portion that can be embedded in a lumen wall. 2. The stent according to claim 1, wherein the lumen wall is a blood vessel wall. 3. The stent according to claim 1, wherein the volume of the implantable portion is 50% or more of the entire volume of the stent. 4. The stent according to claim 1, wherein the material is made of one of a metal and a polymer compound. 5. The stent according to claim 4, wherein said metal is a porous metal. 6. The stent according to claim 1, comprising a metal and a polymer coating layer disposed on the metal. 7. The stent according to claim 4, wherein a physiologically active substance is supported on the porous metal or the polymer compound.