JP2001346885A - Guide wire with dilating function of stenosed site of blood vessel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a guide wire with a function of disturbing blood vessels which is adapted to stenosed site by giving an abrasion to an intermural portion of a blood vessel of a small experipmental animal or to dilate or excise the stenosed site. SOLUTION: The guide wire is constituted of a guide wire body which is coated with a cover layer made of a water-soluble polymer so that the surface thereof develops a state of a low friction resistance the moment it contacts a water based liquid and a knob-like body provided at distal end of the guide wire body and the knob-like part inserted into a blood vessel is vibrated or slidden to abrade or dilate a stenosed site. Microsocpic protrusions and recesses are formed in the entire surface of the knob-like part of a plurality of silts are arranged in the longitudinal direction of the surface to increase the degree of abrasive force while the remains of an abrupted stenosed are recovered.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a guide wire which is inserted into a blood vessel of an experimental animal such as a mouse or a rabbit to cause abrasion and to cause a stenosis on the inner wall of the blood vessel.

[0002]

2. Description of the Related Art In recent years, Japanese people have greatly increased opportunities to eat meat with the westernization of their eating habits. This allows
Atherosclerosis-based ischemic heart disease and atherosclerosis disease are increasing. The direct cause of the disease is mainly caused by the accumulation of cholesterol or the like in the blood vessel, thereby causing a stenosis in the blood vessel and inhibiting normal blood flow in the stenosis.

[0003] Percutaneous angioplasty has been commonly used as a treatment for arterial disease based on atherosclerosis. This is a treatment method in which coronary artery stenosis is released percutaneously without thoracotomy to increase coronary blood flow. That is, a guide wire is inserted from the relevant site by femoral artery puncture, and the distal end is placed at the target coronary artery entrance. Next, using a catheter with a dilatation balloon, the balloon is inserted into the stenosis and the lesion is pressurized.

[0004] Percutaneous coronary thrombectomy has also been performed in which a catheter having a cutter built in a tip cylinder is inserted into a stenosis in a blood vessel, the atheroma is cut off with a cutter, and the atheroma is collected with the tip cylinder. . Further, in the case of restenosis or the like in which good results cannot be obtained by percutaneous coronary angioplasty, percutaneous coronary stenting is performed.

[0005] In order to perform various treatments on a stenosis generated in a blood vessel as described above, first, a guide wire is inserted from the concerned site by femoral artery puncture, and the distal end is placed at a target coronary artery entrance. Next, the balloon of the balloon catheter is introduced into the stenosis by the previously inserted guide wire. Then, the balloon is used to pressurize the stenotic lesion, or a catheter having a built-in cutter at the distal end is inserted into the stenotic portion in the blood vessel, and the stenotic site is cut off by the cutter.

[0006] However, even if the lesion in the blood vessel is pressurized, abraded, or cut off by such treatment, the frequency of initial complications is reduced with the advancement of devices such as guidewires and catheters. At present, restenosis occurs with a probability of 20 to 50% within a few months. Although the introduction of intracoronary stenting reduced the incidence of restenosis by placing the mesh at the balloon and expanding the blood vessels, a reoccurrence rate of around 20% is still observed.

[0007] By examining the pathological image of restenosis thus generated, the outline of the mechanism of restenosis has been gradually revealed. That is, when angioplasty is performed, vascular disorders centering on endothelial damage occur, and as a result, medial smooth muscle cells proliferate and restenosis occurs.

FIG. 6 is a pathological image of a restenosis lesion generated after coronary angioplasty. In FIG. 6, excessive proliferation of smooth muscle cells is observed. In order to prevent restenosis after coronary angioplasty, various drug treatments have been attempted. But,
No drug has proven effective in large clinical trials. In addition, intracoronary radiation has also been attempted. However, there are problems such as thrombosis, carcinogenesis, and smooth muscle cell proliferation at the irradiated site, and the situation is not a condition used for ordinary treatment.

FIG. 7 shows a ballooning disorder of the mouse femoral artery. A hole is made in a micro branch of the femoral artery, and a guide wire is inserted into the femoral artery. The scale is 1mm
It is.

FIG. 8 is a histological image of a mouse femoral artery after ballooning disorder. Immediately after ballooning, apoptosis of medial smooth muscle cells (TUNEL staining positive cells) and expansion of the vascular lumen are observed. Thereafter, hyperproliferation of smooth muscle cells occurs, and the lumen is narrowed.

FIG. 9 shows apoptosis of smooth muscle cells observed by an electron microscope. Chromatin aggregation is observed.

FIG. 10 shows the results of restenosis prevention gene therapy. Cell cycle suppressor gene p2 in blood vessels after balloon injury
When 1 was introduced, proliferation of smooth muscle cells was suppressed.

[0013] Various clinical tests have been carried out using experimental animals to elucidate the mechanism of smooth muscle cell proliferation in more detail and to establish countermeasures. For this reason, a large number of mice more suitable for the experiment have been used by genetic manipulation.

As described above, the vascular injury method is used as one of the treatment methods for arterial diseases, but restenosis due to proliferation of smooth muscle cells is a problem. In order to prevent this restenosis, administration of a drug (solution) and introduction of a gene have been attempted. Therefore, the usefulness of this therapy has been confirmed using mouse microvessels, and attempts have been made to establish a therapy for human microvessels (brain, fingers, peripheral blood vessels).

[0015]

However, since the blood vessels of mice and the like are extremely small at 0.2 to 0.3 mm in the femoral artery, balloons such as those described above for animals such as rabbits and pigs are used. It was extremely difficult to perform the treatment in the blood vessel of a small experimental animal such as a mouse.

That is, first, a guide wire is inserted into a blood vessel, and then a balloon catheter having a size covering the guide wire is inserted along the guide wire.
It has not been possible to apply it to blood vessels of minute size such as mice.

In addition, since such animal experiments must be performed on a large number of animal solids in order to ensure the authenticity of the experiment, the insertion operation of the guide wire and the catheter twice must be performed on many animals. There was a major obstacle to doing it in a short time.

For this reason, the present invention provides a single insertion operation.
An experimental animal suitable for generating a stenosis by scuffing a predetermined portion of the inner wall of a tube of a small experimental animal such as a mouse or expanding or deleting the generated stenosis and artificially causing restenosis. An object of the present invention is to provide a guidewire with a vascular disorder generating function.

[0019]

Therefore, the present invention provides a guide wire inserted into a blood vessel of an experimental animal,
A coating layer formed of a water-soluble polymer substance or a derivative thereof is coated, and a guide wire main body that exhibits a low frictional resistance state when its surface comes into contact with an aqueous liquid; and a knob-shaped member provided at a tip portion of the guide wire main body. Body, and by vibrating or sliding the aneurysm inserted into a predetermined part of the blood vessel, abrasions are made at a predetermined part of the blood vessel inner wall, or a stenosis part generated on the blood vessel inner wall is formed. An object of the present invention is to provide a guidewire with an intravascular stenosis expanding function, which is characterized by expanding. Thus, the guide wire according to the present invention enables the above-described treatment for a mouse or the like having a blood vessel of an extremely small size, and causes a stenosis by applying abrasion to a predetermined portion of the inner wall of the tube with only one insertion operation. This makes it possible to generate restenosis or to artificially generate restenosis by expanding or deleting the generated stenosis.

Here, the guide wire body has a core wire, a wire member covering the core wire, and a coating layer made of the water-soluble polymer substance or a derivative thereof coated on the wire member. The core wire is made of a monofilament plastic member, a stainless steel wire, a piano wire, a titanium wire, a titanium alloy wire or a shape memory metal member,
The wire member is a coil member spirally wound around the core wire, and is formed of a stainless steel wire, a piano wire, a titanium wire, or a titanium alloy wire.

[0021] The water-soluble polymer or the derivative thereof is a cellulose polymer, a maleic anhydride polymer, or an acrylamide polymer. By the action of these substances, the guide wire can be smoothly inserted into a blood vessel.

The shape of the aneurysm may be of various shapes depending on the purpose of the treatment, and may be spherical, ovoid, conical with a narrow tip and a thick rear end, or different in one or more diameters. Some have a disk shape and one or more projections having different lengths.

Further, the degree of abrasion force is increased by forming fine projections or irregularities on the entire surface of the knob-like body or by providing a plurality of slits in the longitudinal direction of the surface.
A porous hole or a slit hole is provided on the surface of the knob-like body, and the inside of the knob-like body is a cavity, and the scum of the peeled constricted portion that enters from the porous hole or the slit is removed. It is formed to be collected.

Further, the tip portion of the guide wire body is formed in a smooth streamline shape, and in combination with the action of the coated coating layer which exhibits a low frictional resistance state when its surface comes into contact with an aqueous liquid, It facilitates introduction into a predetermined site in a blood vessel. Furthermore, the diameter near the distal end of the guide wire body is thinner and more flexible than other portions.

[0025]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The details of a guide wire with an intravascular stenosis expanding function according to the present invention will be described below with reference to the drawings.

FIG. 1 is a diagram for explaining a main part of the present invention. The guide wire main body is composed of a core wire 2 having an appropriate rigidity and a wire member 1 covering the core wire.
Here, the core wire 2 is a single fiber plastic member,
Made of stainless steel wire, piano wire, titanium wire, titanium alloy wire or shape memory metal member. The wire member 1 is a coil member spirally wound around the core wire, and is made of a stainless steel wire, a piano wire, a titanium wire, or a titanium alloy wire.

A plastic or metal nodule 3 is adhered to the vicinity of the distal end 1a of the guide wire body. And the guide wire main body 1 provided with the knob-like body 3
Is inserted into the artery from the inferior part of the mouse, and is sent to a predetermined site while seeing through X-rays. The aneurysm 3 is vibrated or rotated to apply abrasion to the inner wall of the blood vessel or to occur inside the blood vessel. The stenosis can be scraped off. The diameter of the guide wire body near the distal end is gradually reduced compared to the other parts. This increases the flexibility of the wire body and reduces the frictional resistance when moving through the blood vessels of the mouse.

FIG. 2 shows a state in which the tip of the wire according to the present invention is bent into a smooth shape. This is also to reduce the frictional resistance when the wire main body is introduced to a predetermined site in the blood vessel, and the distal end portion 1a of the wire main body 1 is bent into a smooth shape.

Further, in order to impart hydrophilicity to the wire main body 1 and reduce frictional resistance when the wire main body 1 comes into contact with an aqueous liquid, the entire surface of the wire main body 1 is provided with a coating layer made of a water-soluble polymer substance or its dielectric substance. Is coated.

Many natural and synthetic water-soluble polymer substances are known. As natural water-soluble polymer substances, starch, cellulose, tannin and lignin, polysaccharides, and proteins such as gelatin and casein are known. As artificially synthesized water-soluble polymer substances, PVA-based, polyethylene oxide-based, acrylic acid-based, maleic anhydride-based, phthalic acid-based, water-soluble polyester and ketone aldehyde resins, acrylamide-based, polyvinylpyrrolidone, polyimine and Polyelectrolytes and the like are known.

FIG. 3 shows a structure in which fine projections are formed on the surface of the knob-like body 3. Since a plurality of fine projections 5 are formed over the entire surface of the aneurysm 3, the fine projections 5 are vibrated or rotated to apply abrasion to a blood vessel, and to efficiently remove a stenosis portion generated in the blood vessel. be able to.

FIG. 4 shows various shapes of the nubs.
(A) is a spherical shape, (B) is an oval, (C) is a conical shape with a thin tip and a thick rear end, (D) is a single disk or projection, (E)
A plurality of disks or a plurality of protrusions having different diameters. These aneurysms 3 are appropriately selected and used depending on the thickness of the target blood vessel and the condition of the stenosis.

FIG. 5 shows a knob-like body having a slit formed on the surface. A plurality of slits 4 are formed on the surface of the bump 3. If this is inserted into a blood vessel of a mouse and rotated at a predetermined site having a stenosis, it is effective to remove the stenosis. By making the inside of the knob-like body 3 hollow, it is useful to collect and collect some of the exfoliated stenosis from the slit 4 into the inside of the knob-like body 3.

[0034]

As described above, the guide wire with an intravascular stenosis dilatation function according to the present invention is suitable for small animals such as mice having extremely small blood vessels of 0.2 to 0.3 mm in the femoral artery. In addition, it was possible to perform a vascular injury method, thereby facilitating experiments for elucidating the mechanism of restenosis generation due to smooth muscle cell proliferation.

Further, the conventional operation of inserting the guide wire and the catheter twice can be performed by a single operation, so that many animal experiments can be performed in a short time.

In the present invention, since fine projections are formed on the entire surface of the aneurysm provided at the distal end of the guide wire, the guide wire is rotated to efficiently remove a stenosis formed in the blood vessel. can do. Furthermore, a porous hole or a slit hole is provided on the surface of the nodule, and the inside of the nodule is a hollow, and the scum of the peeled constricted portion that enters from the porous hole or the slit is removed. It made it possible to recover.

[Brief description of the drawings]

FIG. 1 shows an example of a guidewire with an intravascular stenosis expanding function according to the present invention.

FIG. 2 is a guide wire according to the present invention in which a distal end portion is smoothly bent.

FIG. 3 shows a knob-like body having fine projections formed on the surface according to the present invention.

FIG. 4 shows various knobs having different shapes according to the present invention.

FIG. 5 shows a knob-like body having a slit formed on the surface according to the present invention.

FIG. 6 shows an example of a pathological image of a restenosis lesion generated after coronary angioplasty.

FIG. 7 shows an example of a ballooning disorder of the mouse aorta.

FIG. 8 shows an example of a mouse femoral artery tissue image after a ballooning disorder.

FIG. 9 shows an example of apoptosis of smooth muscle cells observed by an electron microscope.

FIG. 10 shows the results of restenosis prevention gene therapy.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 Guide wire main-body part coated with the coating layer comprised of a water-soluble polymer substance or its derivative 1a Tip part 2 Core wire 3 Nodule 4 Slit

Claims (14)

[Claims] 1. A guide wire inserted into a blood vessel of an experimental animal, wherein the guide wire is coated with a coating layer composed of a water-soluble polymer substance or a derivative thereof, and has a low frictional resistance state when its surface comes into contact with an aqueous liquid. By vibrating or sliding the nodule inserted into a predetermined portion of the blood vessel, the inner wall of the blood vessel being formed by a guide wire main body having a shape and a nodule provided at the distal end of the guide wire main body. A guide wire with an intravascular stenosis expanding function, wherein a scuff is applied at a predetermined site or a stenosis generated on an inner wall of the blood vessel is expanded. 2. The guide wire body, wherein a core wire, a wire member covering the core wire, and a coating layer composed of the water-soluble polymer substance or a derivative thereof are coated on the wire member. Item 2. The guidewire with an intravascular stenosis expanding function according to Item 1. 3. The core wire is made of a single-fiber plastic member, a stainless steel wire, a piano wire, a titanium wire, a titanium alloy wire, or a shape memory metal member, and the wire member has a spiral shape around the core wire. The guide wire with an intravascular stenosis expanding function according to claim 2, wherein the coil member is made of a stainless steel wire, a piano wire, a titanium wire, or a titanium alloy wire. 4. The intravascular stenosis according to claim 1, wherein the water-soluble polymer or the derivative thereof is a cellulose-based polymer, a maleic anhydride-based polymer, or an acrylamide-based polymer. Guide wire with extended function. 5. The guide wire according to claim 3, wherein the aneurysm has a spherical shape. 6. The guide wire according to claim 3, wherein the bulge has an oval shape. 7. The guide wire according to claim 3, wherein the aneurysm has a conical shape with a thin front end and a thick rear end. 8. The guide wire with an intravascular stenosis expanding function according to claim 3, wherein the shape of the aneurysm is one or a plurality of discs having different diameters. 9. The guide wire with a function of expanding an intravascular stenosis according to claim 3, wherein the shape of the aneurysm is one or a plurality of protrusions having different lengths. 10. The guide wire with an intravascular stenosis expanding function according to claim 3, wherein fine protrusions or irregularities are formed on the entire surface of the aneurysm. 11. The guide wire with a function of expanding a stenosis in a blood vessel according to claim 3, wherein the guide wire has a plurality of slits in a longitudinal direction of the surface of the aneurysm. 12. A porous hole or a slit hole is provided on the surface of the knob-like body, and the inside of the knob-like body is a cavity, and the peeled narrowed portion penetrates from the porous hole or the slit. The guidewire with an intravascular stenosis expanding function according to claim 10 or 11, wherein the guidewire is formed so as to collect scum. 13. The distal end of the guide wire body,
The guide wire with an intravascular stenosis expanding function according to claim 3, wherein the guide wire has a smooth streamline shape. 14. The guidewire according to claim 13, wherein the diameter of the guidewire body near the distal end portion is smaller than that of the other portions and has greater flexibility. .