JPH08245420A - Treating tool using ultrasonic wave - Google Patents

Abstract

PURPOSE: To obtain a medicine administering tool capable of carrying out local treatment without using light irradiation energy. CONSTITUTION: A photosensitive medicine injected into a blood vessel is irradiated with ultrasonic wave to activate the photosensitive medicine by ultrasonic wave energy.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is a catheter for the treatment of various diseases such as thrombus and arteriosclerosis, and for the treatment of reocclusion after treatment of angioplasty such as PTCA, DCA, stent, laser and rotor. The present invention relates to an ultrasonic-wave-based therapeutic instrument that is used by being attached to the tip or the like, and particularly to an ultrasonic-wave-based therapeutic instrument that performs treatment using a photosensitive drug.

[0002]

2. Description of the Related Art For example, myocardial infarction is a disease in which blood flow is blocked due to thrombus or arteriosclerosis in the coronary arteries, oxygen is not sufficiently supplied to the myocardium, and the myocardium becomes necrotic.

One of the treatment methods for this myocardial infarction is medical thrombolytic therapy. In this medical thrombolytic therapy, a thrombus is dissolved by a drug by oral administration of the drug or intravascular injection.

However, in this medical thrombolytic therapy, the drug component is administered to the affected part by absorbing the drug into the blood and circulating this blood in the body, and therefore, compared with the amount of the drug administered, the affected part is compared. Since the amount of the drug absorbed into the skin is very small, there was a problem that the drug administration efficiency to the affected area was very poor. In addition, there is a problem that increasing the drug concentration to obtain an effective blood concentration causes side effects on other organs.

On the other hand, mechanical vasodilation therapy and the like are known as those for intensively treating thrombotic arteriosclerosis. This vasodilation therapy is based on PTCA (percutan).
eous transluminal coronar
y angioplasty: percutaneous coronary angioplasty). A guide catheter is introduced percutaneously from the patient's thigh to the coronary artery entrance under fluoroscopy, and a catheter with a balloon at its tip is guided. In this method, the lesion is guided by a wire and the balloon is inflated there to expand the stenosis of the coronary artery and increase the coronary blood flow. There is also a method of removing the affected area with a drill or a laser.

However, this vasodilation therapy has a problem that restenosis occurs at a high rate of 30 to 50% within a few months after the operation. For this reason, after a certain period of time has passed since the surgery, re-examination is performed using coronary angiography,
If there was restenosis, vasodilation therapy was repeated again, and if the stenosis could not be treated, more extensive coronary artery bypass surgery was required.

Further, in order to prevent restenosis, when performing vasodilation therapy, a wire mesh cylindrical body called a stent is inserted into the narrowed portion of the blood vessel and the balloon is expanded to expand the diameter of the cylindrical body. By doing so, the wall surface of the blood vessel is reinforced. However, even in this case, reocclusion occurs at an extremely high frequency.

The above-mentioned restenosis of the blood vessel causes damage to the intima of the blood vessel when a balloon or a stent is inserted into the blood vessel.
It is thought that this occurs because hyperplasia occurs due to intimal proliferation to repair this damage.

Recently, in order to prevent restenosis,
Photofrin II, HpD (hematoporphyrin derivative), DHE / E (dihematoporph)
rin and ether), Chloroalum
inum sulphated phthalocy
anine, 8-methoxypsoralen, 5
Studies on photochemotherapy using photosensitizing drugs such as -amino-levulinic acid have also been conducted (see, for example, Paolo Ortu et al .: "Photod.
dynamic Therapy of Arterie
s ", CIRCURATION (Journal of the American Circulation Society),
1992, Vol. 85, pp. 1189-1196).

The photosensitizing drug is activated when it is exposed to light and exerts its medicinal effect. Therefore, by injecting the photosensitizing drug into the body and then irradiating the affected area with light, the drug is irradiated only to the affected area. Can be operated. Therefore,
Photochemotherapy using a photosensitizing drug has an advantage that side effects are less likely to occur on parts other than the affected part.

However, in photochemotherapy using a photosensitizing drug, it is necessary to irradiate light from outside the body, and since the light has a reach of at most about 1 cm within the human body tissue, the affected area near the surface of the body is affected. However, there is a problem that the therapeutic effect can only be obtained. In addition, when trying to reach the affected area away from the surface of the body, it is necessary to increase the irradiation energy of the light, but in this case, there is a risk of giving a feeling of heat to the patient or modifying the tissue. In addition, there is a problem that the device becomes large and the cost of the device becomes high. In addition, when photochemotherapy is applied to endovascular treatment, red blood cells absorb light.Therefore, current intravascular phototherapy requires blocking the blood flow in blood vessels in the affected area and flowing a clear liquid instead of blood. There is a problem that it takes time and effort.

[0012]

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a drug administration device capable of performing local treatment without using irradiation energy of light.

[0013]

An ultrasonic-wave therapeutic instrument of the present invention is an ultrasonic-wave therapeutic instrument that is inserted into a blood vessel by irradiating a light-sensitive drug injected into the blood vessel with ultrasonic waves. , Activating the photosensitive drug.

The ultrasonic therapeutic device of the present invention is an ultrasonic therapeutic device for irradiating an ultrasonic wave from the outside of the body to the inside of the body, and the photosensitive drug injected into the blood vessel is irradiated with the ultrasonic wave. It is characterized by activating a photosensitive drug.

[0015]

The photosensitizing drug is injected into the blood vessel through a catheter or by injection. At the tip of the catheter,
An ultrasonic wave generator is provided, and the ultrasonic vibration from the ultrasonic wave generator is applied to the photosensitive drug in the blood vessel. Since the photosensitizing drug is excited not only by light energy but also by ultrasonic energy, the photosensitizing drug is activated by irradiation of ultrasonic waves. Therefore, the photosensitive drug is effective only in the vicinity of the affected area, and local treatment is possible.

Ultrasonic energy can also be applied from outside the body. Unlike light energy, ultrasonic waves are less attenuated when passing through tissues, so that even when the affected area is far from the body surface, it is possible to activate the photosensitive drug in the vicinity of the affected area.

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The features of the present invention will be specifically described below based on embodiments with reference to the drawings.

FIG. 1 is a schematic view showing a mode of use of the ultrasonic wave treatment instrument of the present invention. An ultrasonic wave generator 3 is provided at the tip of a catheter 2 made of silicon or Teflon that is inserted into the blood vessel 1.

FIG. 2 is an enlarged sectional view of the ultrasonic wave generator 3. The ultrasonic generator 3 includes a cylindrical piezoelectric element 4, a cylindrical inner electrode 5 formed by vapor deposition of silver on the surface of the inner peripheral surface of the piezoelectric element 4, and an outer peripheral surface of the piezoelectric element 4. And a cylindrical outer electrode 6 similarly formed on the surface of the. The inner electrode 5 and the outer electrode 6 are
It is provided in a state of being electrically insulated from the outside by coating its surface with an insulator. Lead wires 7 and 8 are connected to the inner electrode 5 and the outer electrode 6, respectively, and these lead wires 7 and 8 are led out along the inside of the catheter 2 to the root of the catheter 2 and drawn out of the body. . The tip of the ultrasonic generator 3 is covered with a disk-shaped lid 9. The ultrasonic generator 3 has a diameter of, for example, about 1 mm and an axial length of about 1 mm.
However, the size is not limited to this, and can be variously changed according to the type and state of the affected area to be treated.

An electric signal of ultrasonic frequency is applied between the inner electrode 5 and the outer electrode 6 of the ultrasonic generator 3, and the piezoelectric element 4 mechanically vibrates in the direction of arrow P at the ultrasonic frequency, This ultrasonic vibration is applied to the blood 1d containing the photosensitizing drug in the blood vessel 1 and the inner elastic plate 1a of the blood vessel 1. At this time, this ultrasonic vibration is as shown by an arrow Q in FIG.
Since it is radiated in the direction perpendicular to the surface of the piezoelectric element 4, that is, in the direction perpendicular to the axis of the ultrasonic wave generator 3, the internal elastic plate 1a is efficiently irradiated with ultrasonic vibrations. When ultrasonic vibration is applied to the inner elastic plate 1a, the tissue of the inner elastic plate 1a is loosened by the ultrasonic vibration and the drug is easily absorbed.

[Experimental Example] An experiment (Experiment A) was carried out to confirm the effect of suppressing the internal elastic plate hyperplasia by using the ultrasonic generator 3 described above.

A Japanese white rabbit was anesthetized with Nembuntar (25 mg / kg) under a balloon catheter (F
, abdominal aortic elastic plate 1a
Was injured about 7 cm. In FIG. 1, A indicates the intravascular elastic plate damage range. 1b is a smooth muscle and 1c is an external elastic plate. Immediately after the blood vessel damage, Photofrin II (5 mg / kg), which is known as a photosensitizing drug, was injected into the ear vein, and at the same time, the ultrasonic generator 3 shown in FIG. Ultrasonic waves were irradiated from within the blood vessel for about 10 minutes over about 1 cm. In FIG. 1, B indicates an ultrasonic irradiation site, and 1d indicates blood containing a photosensitive drug. Ultrasonic intensity is 0.3 W / cm ² , frequency is 1.3
It was set to MHz.

After 4 weeks, the blood vessels of the ultrasonic irradiation site B and the ultrasonic non-irradiation sites C and D before and after the cutting were cut out to prepare a cross-sectional blood vessel sample (EVG staining), and the degree of hyperplasia was measured. The degree of hyperplasia depends on the computer (Macintosh).
Image processing using the Sh Quadra 800) allows for intimal / medial (Media)
al) The area ratio was measured.

FIG. 3 is a schematic diagram showing a blood vessel in a hyperplastic state. 4 (a) and 4 (b) are cross-sectional views of FIG. 3 taken along line X-X and line Y-Y in a direction orthogonal to the length direction of the blood vessel. In the figure, 1e shows an overforming part.

In order to confirm the influence of only ultrasonic waves,
Immediately after the intravascular injury, the same experiment (Experiment B) as the above-mentioned conditions was performed except for Photofrin II administration.

The significant difference test between the ultrasonic wave irradiation site and the ultrasonic wave non-irradiation site is conducted by Student's test (Paire).
d, p <0.05), and other than that, ANOVA was used.

The area of the intima of the blood vessel was taken to be the cross-sectional area from the surface of the lumen, that is, the surface of the hyperplasia to the internal elastic plate 1a, and the area of the media of the blood vessel was taken to be the cross-sectional area from the internal elastic plate 1a to the external elastic plate.

The experimental results are shown below.

[0029]

[Table 1] From the results of Experiments A and B, intimal proliferation is not suppressed by single administration of Photofrin II or single treatment of ultrasonic waves, and therapeutic effect is improved by combined administration of Photofrin II and ultrasonic irradiation. It was confirmed.

Although ultrasonic waves are emitted from the inside of the blood vessel in the above-described embodiment, for example, US Pat.
Devices such as those described in US Pat. No. 158,071 that are capable of focusing ultrasound waves into specific parts of the body may be used to provide ultrasound energy to the photosensitive drug from outside the body. .

[0031]

As described above, according to the present invention, focusing on the fact that the photosensitizing drug is also sensitive to ultrasonic waves, ultrasonic waves are emitted instead of light. As a result, the drug can be locally applied to the affected area located away from the surface of the body to effectively treat the affected area.

[Brief description of drawings]

FIG. 1 is a schematic view showing a usage mode of an ultrasonic therapeutic instrument of the present invention.

FIG. 2 is an enlarged cross-sectional view of an ultrasonic wave generator.

FIG. 3 is a schematic diagram showing blood vessels in a hyperplastic state.

4A and 4B are cross-sectional views of FIG. 3 taken along line X-X and line Y-Y in a direction orthogonal to the length direction of the blood vessel.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Blood vessel, 1a ... Inner elastic plate, 1b ... Smooth muscle, 1c ... Outer elastic plate, 1d ... Blood, 1e ... Hyperplasia part, 2 ... Catheter,
3 ... Ultrasonic generator, 4 ... Piezoelectric element, 5 ... Inner electrode, 6
... Outer electrodes, 7, 8 ... Lead wires, 9 ... Lid

Claims (2)

[Claims] 1. A therapeutic device utilizing ultrasonic waves, which is inserted into a blood vessel, wherein the photosensitive drug injected into the blood vessel is irradiated with ultrasonic waves to activate the photosensitive drug. Ultrasonic treatment equipment. 2. A therapeutic device utilizing ultrasonic waves for irradiating ultrasonic waves into the body from outside the body, which comprises irradiating the photosensitive drug injected into a blood vessel with ultrasonic waves to activate the photosensitive drug. Characteristic ultrasonic treatment equipment.