JP4966640B2 - Photodynamic therapy device and method of using the same - Google Patents

Description

  The present invention relates to a photodynamic therapy apparatus capable of treating only a deep lesion while preserving a shallow part, which is a healthy part of a living body, without damaging it, and a method of using the same.

  Photodynamic therapy (also called photodynamic therapy: PDT, photochemical therapy) has been studied for application to various treatments in addition to endoscopic treatment of early cancer. PDT means that a photosensitive substance (hereinafter referred to as a PDT drug) is administered by a method such as intravenous injection, selectively absorbed and accumulated in a lesion such as a cancerous tissue to be treated, and then irradiated with a light beam such as a laser beam. This is a treatment method for treating a lesion by irradiation.

  A PDT drug has a property of selectively accumulating in a lesioned part and a property of being activated when irradiated with light. The activation of the PDT drug means that oxygen around the PDT drug becomes singlet oxygen (active oxygen), and the singlet oxygen exerts strong oxidizing power and can damage the cells in the lesion.

  PDT using such singlet oxygen features has the following mechanism. When the PDT drug taken into the lesion is excited by light irradiation, the energy of the excited photosensitizer is transferred to oxygen present in the lesion, generating active singlet oxygen (active oxygen), This singlet oxygen necroses cells in the affected area by its strong oxidizing power. In other words, PDT requires a PDT drug in the lesion, excitation light that excites the PDT drug, and oxygen that is activated by the excited PDT drug. This is an extremely important factor in the treatment of generating oxygen.

  In PDT, when a PDT drug is accumulated in a lesion in the deep part of the living body and irradiated with excitation light, the lesion in the deep part of the living body can be treated, which is an extremely effective means for the treatment of the deep part of the living body. That is, it is not preferable to damage the cells of the healthy part on the irradiation means side that irradiates the excitation light with respect to the lesioned part, and it is desirable to treat the cells of the healthy part while preserving them. Moreover, in order to shorten the time concerning treatment, it is preferable that the treatment can be started even in a situation where a sufficient accumulation time does not pass after the administration of the PDT drug and there is little difference in drug concentration between the lesioned part and the healthy part.

  As such a conventional treatment method, for example, there is a method in which a PDT drug is activated only in a lesioned part by focusing a laser beam on the lesioned part (see Patent Document 1).

  However, in this method, if the focus of the laser beam is deviated or the intensity of the laser beam or the concentration of the drug is changed, the healthy part may be damaged, and it is difficult to detect the damaged shallow part.

  Therefore, the present inventors conducted extensive studies on pulsed laser irradiation conditions such as the PDT drug, the oxygen concentration of the lesion, and the peak intensity of the laser. As a result, the peak intensity of the irradiated laser light was changed from low to high intensity. As the peak intensity increases to a certain level, the PDT treatment efficiency (the degree of injury of the lesioned tissue) increases. However, if the peak intensity becomes too high, the treatment efficiency decreases. .

  This is because, in a disease where the lesion is covered with a healthy part, if the treatment depth is examined and the peak intensity of the laser is controlled, it can be used for the treatment of only the deep part without damaging the shallow part. Previously proposed as an apparatus (see Patent Document 2).

  In addition, in relation to the photodynamic therapy apparatus according to this proposal, as a detection means for detecting the activation of the PDT drug, fluorescence generated from singlet oxygen and the amount of light scattered outside the living body and emitted outside the living body Since it is possible to use the concentration of the PDT drug, the partial pressure of oxygen in the living body, or the inspection light transmitted through the surface of the living body, these have also been proposed (see Patent Document 3).

  The so-called “shallow preservation phenomenon” can be treated only in the deep part without damaging the shallow part, so the following three effect attenuation phenomena can be considered, all of which are the results of experiments using solution systems and cells. Proven.

(1) Drug bleaching The phenomenon in which a photosensitizer is destroyed by the generated singlet oxygen. In the shallow part of a living body that has received high-intensity pulse irradiation, the photosensitizer is rapidly destroyed by the singlet oxygen that is generated. Decreases.

(2) Local oxygen depletion Photosensitizers consume oxygen in the vicinity to generate singlet oxygen, and this supplemental oxygen supply is supplied by diffusion from the surroundings, and therefore received high-intensity pulse irradiation. In the shallow part of the living body, oxygen is locally depleted in the vicinity of the photosensitive substance, and oxygen supplementation from the periphery is not in time, and the therapeutic effect is reduced.

(3) Absorption saturation Because the amount of light energy that can be absorbed by a photosensitive substance is limited (supersaturated absorption phenomenon), in the shallow part of a living body that has received high-intensity pulse irradiation, even if more light energy is administered, it is efficient. Cannot be taken in automatically, and the therapeutic effect is reduced.

  However, it is difficult to explain the situation that “therapeutic effect cannot be obtained at all in the shallow area” as seen in the results of the InVIVO experiment with these phenomena alone.

In particular, in the shallow area, which is a thin and small local organization, it is not certain whether or not the injury will recover if the degree of injury is low, and which of the three phenomena may be the dominant factor. Not sure.
US Pat. No. 5,829,448 WO 2004/112902 A1 WO 2006/049132 A1

  The present invention has been made on the basis of knowledge obtained as a result of earnest research under the circumstances described above. In photodynamic treatment, the laser blood flow is reduced depending on the intensity of the laser beam, and the laser is focused on the laser beam. By controlling the intensity of light, the blood flow flowing in the shallow part of the living body is adjusted, and the increase or decrease in the amount of PDT drug accompanying the increase or decrease of the blood flow prevents the damage to the shallow part of the living body, while ensuring only the affected part. It is an object of the present invention to provide a photodynamic therapy device that can be treated and that has a lower physical and mental burden on the patient and can provide a higher therapeutic effect, and a method of using the same.

The photodynamic therapy device according to the present invention is a photodynamic therapy device for treating a lesion in a deep part of a living body using a photosensitizer activated by light, and activates the photosensitizer. irradiating means for irradiating light to the lesion, and a radiation control means for controlling the peak intensity of the light to reduce the blood flow through the shallow blood vessel in the irradiation unit side of the lesion The irradiation control means includes: a detection means for detecting a blood flow volume in the shallow portion; and the irradiation means for adjusting the contraction of the blood vessel in the shallow portion based on a detection result of the detection means. Control means for controlling the peak intensity of the light .

  In the present invention, the blood vessels in the shallow part of the living body are spasmed when irradiated with high-intensity pulsed laser light, and the blood flow is greatly reduced, and when the low-intensity pulsed laser light is irradiated, the blood vessels are spasmless and the blood flow is reduced little. In the inventions according to claims 1 and 8, in the photodynamic therapy apparatus, by irradiating the living body with high-intensity pulsed laser light, in the living body shallow part that is shallower than the lesioned part, The flowing blood flow can be reduced, the supply of PDT drug and oxygen can be cut off, the generation of singlet oxygen by the PDT drug can be prevented and the tissue can be stored without being killed. By using this attenuation, it is possible to prevent the blood vessels from spasm and decrease the blood flow, and to kill the tissue of the lesioned part by the continuously supplied PDT drug and oxygen. As a result, even in various lesions with various locations and types, only deep lesions can be treated more reliably while preserving or preserving the shallow part of the living body.

  In addition, in the photodynamic therapy device, the irradiation part is pulse-irradiated by the irradiation means, and the peak intensity of the light activated by the PDT drug is controlled by the irradiation control means, so that the blood flow through the blood vessel is reduced. The peak intensity of light can be controlled, the blood flow rate can be reduced, the superficial preservation phenomenon can be made more reliable, and the therapeutic effect can be further improved.

In addition, it is not necessary to wait until the concentration difference between the lesioned part and the healthy part on the irradiation means side that irradiates the excitation light as in the conventional case, and the treatment can be started when the PDT drug reaches the lesioned part. Therefore, there is no need to stay in a dark room where no visible light reaches, and the physical and mental burden is greatly reduced in both patients and medical workers. In addition, the irradiation control means detects the blood flow volume shallower than the lesioned part by the detection means, and the control means controls the peak intensity of the light and adjusts the blood vessel contraction based on the detection result. It is possible to perform an accurate and reliable treatment in accordance with the above, and exhibit an excellent therapeutic effect.

In the invention according to claim 6 , since the photosensitive substance has a characteristic that it is activated by light having a peak intensity in a predetermined range and is not substantially activated by light having a peak intensity outside the predetermined range. By only irradiating light with intensity, the photosensitive substance can generate singlet oxygen and kill the tissue.

In the invention according to claim 2 , since the detection means detects the blood flow volume by measuring the light quantity of the irradiation light and the reflected light, the detection of the blood flow volume becomes direct and extremely accurate. Accurate and reliable treatment suitable for the patient can be achieved, and higher therapeutic effects can be exhibited.

In the invention described in claim 3 , since the detecting means detects the blood flow volume from the ratio of the color tone corresponding to the blood or the number of blood vessels in the shallow image, the detection of the blood flow volume is straightforward and extremely accurate. Thus, a higher and superior therapeutic effect can be exhibited.

According to the fourth aspect of the present invention, the irradiation of the high-intensity pulse is started, and after a predetermined time has elapsed, the shallow blood vessel is spasmed. Utilizing this phenomenon, the predetermined time is measured by the control means, and the peak intensity of the light to be irradiated is controlled so as to be equal to or less than the blood flow volume before the predetermined time, so that the high intensity pulse can be irradiated unnecessarily. In addition, detection of the blood flow in the shallow area is more reliable, and extremely accurate treatment is possible.

In the invention according to claim 5 , the blood flow volume flowing in the shallow blood vessel is reduced immediately after the start of light irradiation until the initial blood flow suppression time, and after the initial blood flow suppression time has elapsed, until the light irradiation ends. If the peak intensity of light is controlled so that the contraction of the blood vessels in the shallow area is maintained during this period, the effect will be improved by killing the tissue in the deep lesion area while preserving the shallow area. Greatly improved.

(Premise of the present invention)
First, an outline of knowledge regarding changes in laser light intensity and blood flow in PDT, which is a premise of the present invention, will be described. InVIVO experiments were carried out using so-called tumor-bearing mice that produced cancer tumors by subcutaneously implanting prostate cancer cells. In the experiment, a PDT drug was applied to a tumor-bearing mouse, and after irradiating a cancer tumor with high-intensity pulsed laser light and low-intensity pulsed laser light one hour later, The blood flow rate in the deep part was measured by measuring the blood flow rate with a laser Doppler blood flow meter.

  The experimental results show that the blood flow velocity on the living body surface is reduced by 85% when irradiated with high-intensity pulsed laser light, and the blood vessels at the irradiated part of the pulsed laser light disappeared when the shallow area is visually observed. It was. At the time of irradiation with low-intensity pulsed laser light, the blood flow rate was reduced by about 31% compared to the blood flow rate before irradiation, and the presence of blood vessels on the surface of the living body could be clearly determined by visual observation.

  Such vasoconstriction action is caused by the influence of three factors, i.e., stimulation by generated singlet oxygen, stimulation by high-intensity pulsed laser light, and thermal stimulation produced by high-intensity pulsed light. Conceivable. Although it is considered that blood flow has been reduced by a transient thrombus, the blood flow volume is likely to be reduced due to spasm because of the resumption of blood flow after treatment.

  On the other hand, at the deep part, the laser light causes a diffusion phenomenon by living tissue to become diffused light even when irradiated with high intensity pulse laser light or low intensity pulse laser light. Does not decrease.

  Thus, the fact that the blood flow volume on the surface of a living body is greatly reduced by irradiating with a high-intensity pulsed laser light means that a PDT drug inevitably moved by the blood flow, and singlet oxygen generated by this PDT drug. It also means that it is reduced and depleted. This means that even if a high-intensity pulsed laser beam is irradiated on the living body surface, the therapeutic effect by PDT on the living body surface cannot be obtained, and the cells will not be necrotic.

  The fact that the presence or absence of such blood flow affects the production of singlet oxygen was verified by experiments. In the experiment, an aqueous solution in which a photosensitive substance and protein are dissolved is used, and the blood flow arrest state is modeled by an aqueous solution that is stored, and the blood flow state is modeled by a solution that continuously flows in the flow cell. The state of fluorescence emitted by singlet oxygen generated by excitation of the PDT drug was verified by irradiation with intense pulsed laser light. In the former storage system, the fluorescence from the drug decreased sharply 20 seconds after the start of irradiation. On the other hand, in the latter flow system, conversely, singlet oxygen fluorescence increased. This means that when blood flow is lost, the supply of PDT drug and oxygen is cut off, and singlet oxygen that produces a therapeutic effect is not generated, and the phenomenon of reduction in the amount of PDT drug due to irradiation with high-intensity pulsed laser light has been confirmed. did it.

  From this point, the blood vessel in the shallow part of the living body contracts (convulsions) after the start of high-intensity pulse irradiation, the supply of the PDT drug and oxygen is cut off, and the photodynamic effect is suppressed in about 20 seconds. become. Here, the time from the start of laser light irradiation to the state where blood flow is reduced is referred to as “initial blood flow suppression time”.

  On the other hand, high-intensity pulsed laser light that reaches the deep part (lesioned part) is attenuated by living tissue or blood, so that vasoconstriction in the deep part does not occur and singlet oxygen is generated gently over a long period of time. It was also found to continue.

  In addition, it has been found that blood vessels that have been convulsed by high-intensity pulsed laser light dilate after a short period of time after irritation, and blood circulation is resumed. Saved.

  As a result, when the blood vessels in the shallow part of the living body are spasmed by irradiation with high-intensity pulsed laser light and the blood flow volume is greatly reduced, the deep part can be treated while preserving the shallow part.

  Fig. 1 is a summary of the results of experiments on the preservation mechanism of the shallow part by irradiation with high-intensity pulsed laser light, and is a schematic diagram showing the time. The horizontal axis represents time, and the vertical axis represents the shallow part and deep part (lesioned part). Qualitatively shows blood flow, singlet oxygen and cumulative singlet oxygen. In the drawing, the solid line indicates the situation in the shallow part, and the broken line indicates the condition in the deep part. Further, it is assumed that the PDT drug has already been administered at the start of irradiation with the high-intensity pulsed laser beam and has already been distributed in the living body including the lesioned part.

  The first stage shows the irradiation of high-intensity pulsed laser light by ON and OFF. The state where the high-intensity pulsed laser beam is irradiated is “ON”, and the state where the irradiation is stopped is “OFF”. High-intensity pulsed laser light irradiation starts irradiation and ends irradiation after a predetermined time.

  As shown in the second stage, the blood flow volume in the shallow portion changes due to the irradiation with the high-intensity pulsed laser light. In the shallow blood flow, the initial flow gradually decreases to approximately 0 over 20 seconds after the start of irradiation, and decreases to approximately 0. However, in the deep blood flow, high-intensity pulsed laser light is diffused / absorbed by a living tissue, etc. Since the intensity of the blood flow decreases, the blood flow does not change. Strictly speaking, in the experiment, the blood flow gradually decreased slightly with the passage of time, but here, for the sake of simplicity, the display is constant for convenience.

  The singlet oxygen production amount shown in the third stage is greatly affected by blood flow. In the shallow area, since the blood flow rate decreases, the supply of new PDT drug and oxygen is cut off, and the amount of singlet oxygen generated decreases rapidly with a decrease in blood flow. However, since there is no change in blood flow in the deep part, singlet oxygen is constantly generated.

  The accumulated singlet oxygen shown in the fourth stage has a direct effect on the therapeutic effect. However, in the shallow part, the production decreases in about 20 seconds after the start of irradiation. There is only a small amount of oxygen. However, since the generation of singlet oxygen continues throughout the entire region from the start to the end of irradiation, the accumulated singlet oxygen amount is extremely large.

  When the irradiation is completed in this way, in the shallow portion, the blood vessel that has been blocked by the irradiation of the high-intensity pulsed laser light is gradually opened, and the blood flow is resumed. Although the time required for resumption varies depending on the individual, blood circulation is restored before the superficial tissue is necrotic. In addition, as a reference on this point, “Heat and Photolytic Nitric Oxide are essential factors for light-Induced vascular tension” published in Lasers in Medical Science Volume 15: 181-187 (Matsuo H. et al.) )

  Therefore, in the shallow part, the supply of oxygen to the cells is resumed by resuming the blood flow, and the shallow cells are preserved without being killed. Even if the cell is damaged by a small amount of singlet oxygen, it can be recovered. On the other hand, in the deep part, cell damage is advanced due to a large amount of singlet oxygen, and even if there is a blood flow, it does not recover and the cell is killed to achieve a therapeutic effect.

  As described above, in the present invention, when a living body is irradiated with a high-intensity pulsed laser beam, the supply of the PDT drug and oxygen is cut off due to a decrease in blood flow volume in the shallow area, the generation of singlet oxygen is reduced, and cell damage is reduced. On the other hand, in the deep part, the blood flow rate does not decrease due to the diffusion of the high-intensity pulsed laser light, the PDT drug and oxygen are supplied, the cumulative singlet oxygen amount increases, and the cells are damaged. However, although the shallow portion preservation effect is largely caused by a decrease in the shallow blood flow rate due to the irradiation of the high-intensity pulsed laser beam, the synergistic effect of this blood flow decrease phenomenon and the above three “effect attenuation phenomena”. It is considered that only the deep part (lesioned part) can be treated with the effect of preserving the shallow part of the living body.

  Here, a vascular shutdown effect is known as an action of the photodynamic therapy. In general, the blood vessels connected to the lesion site are coagulated and contracted due to the therapeutic effect of PDT to cause irreversible contraction, or the blood supply is blocked by the formation of a thrombus, thereby stopping the supply of nutrients to the lesion site. Refers to the state. In this case, resumption of blood flow is not observed at the site of the vascular shutdown effect. In this respect, the blood flow reduction at the shallow portion in the present invention is different in that it causes a spasm in which the blood flow resumes after the treatment is completed.

An embodiment of the present invention based on such knowledge will be described.
(First embodiment)
2 is a schematic perspective view of the photodynamic therapy device according to the first embodiment, FIG. 3 is a block diagram showing a schematic configuration of the photodynamic therapy device, FIG. 4 is a front view of the catheter, and FIG. (D) to (D) are views showing the distal end of the catheter.

  As shown in FIGS. 2 and 3, the photodynamic therapy device 1 includes an irradiation unit 11 that pulse-irradiates a lesioned part 41 with laser light, and an irradiation control unit 20 that controls the peak intensity of light from the irradiation unit 11. Have. In FIG. 2, only the distal end portion of the irradiation means 11 is shown in an enlarged manner, and the symbol “SW” in FIG. 2 is a foot switch for laser light irradiation.

  The irradiation means 11 is a thin and long treatment catheter 10 whose tip is inserted into the living body, a light irradiation portion 13 provided at the tip of the treatment catheter 10, and the treatment catheter 10 is inserted and extended. Are connected to the treatment apparatus main body 20a, and have an optical fiber F for guiding the light from the light source 21 to the light irradiation part 13.

  The irradiation control means 20 is a detection means 23 for detecting the blood flow rate in the shallow portion 42, and the light emitted by the irradiation means 11 so as to adjust the contraction of the blood vessels in the shallow portion 42 based on the detection result of the detection means 23. And a light branching unit 24 to which the light source 21 and the detection unit 23 are connected.

  Further details will be described. The treatment catheter 10 in the irradiation means 11 only needs to be able to reach the lesioned part 41 to be treated. For example, when treating arteriosclerosis, a catheter for blood vessels, and for treating prostate cancer or prostatic hypertrophy, it is used for the urethra. Use a catheter.

  The optical fiber F inserted through the inside of the treatment catheter 10 is not particularly limited as long as it can transmit the energy of the light from the light source 21. For example, the diameter of the optical fiber F is about 0.05 to 0.6 mm. Is.

As shown in FIG. 4, the treatment catheter 10 is provided in the vicinity of the base 12 connected to the treatment apparatus body 20 a, the light irradiation unit 13 provided at the distal end inserted into the living body 40, and the light irradiation unit 13. and a contrast marker M _1, and a depth marker M ₂ provided near the center.

  The material constituting the entire treatment catheter 10 is composed of a polymer resin if it is a flexible catheter, and is composed mainly of metal if it is a rigid catheter. Other materials having a strength suitable for insertion into a living body may be used, or a coil spring within the thickness of the treatment catheter 10 or a wire extending in the axial direction may be reinforced.

  The light irradiation unit 13 is made of a light transmissive material such as synthetic quartz, polyethylene terephthalate or polycarbonate so that the laser light guided by the optical fiber F can be irradiated without being attenuated by the treatment catheter 10 itself. It is made of a highly transparent resin.

The contrast marker M ₁ may be an X-ray opaque marker for enhancing X-ray visibility or a marker for enhancing MRI contrast. For example, the contrast marker M ₁ may be visible on the outer surface of the treatment catheter 10. It is formed by providing a certain tungsten powder. As a result, the position of the distal end portion of the treatment catheter 10 can be easily confirmed. The depth marker M ₂ may be the same as the contrast marker M ₁ , but a plurality of depth markers M ₂ are provided at predetermined intervals in the axial direction and used when the treatment catheter 10 is inserted into the living body (reference numeral “33 in FIG. 7). a tip portion of the "reference), it is possible to know the insertion depth in relation to the depth marker M _2.

  In the case of treating the prostate, for the purpose of bringing the light irradiation unit 13 into contact with the tissue, and in the case of treating arteriosclerosis, the blood flow in the lesioned part 41 at the time of light irradiation. Therefore, a balloon that expands and contracts by supplying and discharging liquid or gas inside may be provided near the distal end of the treatment catheter 10. However, this balloon may have a blood perfusion function in order to secure a blood flow.

As the distal end portion of the treatment catheter 10, various types can be adopted as shown in FIG. Tip shown in FIG. 5 (A) is a typical example, in which the most recent position of the light-emitting section 13 provided with a contrast marker M _1.

  The tip shown in FIG. 5B is for irradiating diffused light, and light that has passed through the optical fiber F provided coaxially with the treatment catheter 10 is diffused by the light diffuser 14 and irradiated outside the catheter. Is done. Examples of the light diffuser 14 include a material in which a light diffusing substance such as alumina powder is distributed in a transparent material such as synthetic quartz or epoxy resin, or diffused light by attaching a minute scratch around the optical fiber F. There are things that give rise to.

  The tip shown in FIG. 5 (C) is a side-fired type, and can maintain the intensity of the pulsed laser light as compared with the diffused light type shown in FIG. 5 (B), so that the output of the pulsed laser light is suppressed. There is an advantage that can be. As means for laterally emitting pulsed laser light, for example, a mirror 15 for defining the light emission direction is provided at the output-side tip of the optical fiber F, or a prism is provided depending on circumstances. As the mirror 15, for example, a rigid quartz substrate, a metal plate, or a metal vapor deposited on a plastic member can be used.

The area range of the pulsed laser beam irradiated to the side illuminates the lesion 41, it is necessary to avoid influence of heat to the surrounding tissue, preferably 0.5cm ² ~3cm ^2. Even if the irradiation range is local and narrow, if the treatment catheter 10 is rotated according to the size of the lesioned part 41 to change the direction of irradiation and the lesioned part 41 is irradiated a plurality of times, the lesioned part 41 can be completely treated.

  The tip shown in FIG. 5 (D) is provided with a tip 16 for puncture, and when used under X-ray contrast or under laparoscope with a laparoscope / thoracoscope, it is directed from the hand to the target lesion 41. And can be inserted straight.

  Next, the irradiation control means 20 will be described. First, in FIG. 3, the light source 21 in the irradiation control means 20 is a part which irradiates a laser beam. As the laser, a semiconductor laser, a dye laser, a double wavelength of a variable wavelength near infrared laser, or the like can be suitably used. The irradiated laser beam may be continuous or pulsed laser beam. However, in the case of continuous irradiation, if the peak intensity is set to a certain level or more, the irradiated part is denatured by heating. Not very suitable. It is desirable to use pulsed light when performing shallow preservation treatment. A pulse of pulsed laser light means a pulse having a pulse width of 1 ms or less.

  The control unit 22 adjusts the output peak intensity of the laser light output from the light source 21 so that the output peak intensity of the laser light becomes a peak intensity within a predetermined range suitable for treatment in the lesion part 41 according to the depth of the lesion part 41. Or control light irradiation conditions such as repetition frequency.

  The detection means 23 includes a light branching unit 24 that separates the laser light and the return light irradiated toward the lesioned part 41, a blood flow rate calculation unit (blood flow rate calculation) that measures the amount of the return light and calculates the blood flow rate. Means) 25.

  The light branching unit 24 has a function of guiding laser light from the light source 21 adjusted by the control unit 22 to the light irradiation unit 13 and a function of guiding return light from the light irradiation unit 13 to the light amount measuring unit 25. have.

  The blood flow rate calculation unit 25 is connected so as to calculate the blood flow rate of the shallow portion 42 from the amount of return light detected by the sensor 26 provided in the vicinity of the light irradiation unit 13 and to transmit the blood flow rate to the control unit 22.

  Since the irradiated laser light has the property of being absorbed by blood, the amount of return light decreases when there is a blood flow, and increases when the blood flow decreases. By utilizing this point, as shown in FIG. 3, the detection unit 23 detects the amount of return light detected by the sensor 26 provided in the vicinity of the light irradiation unit 13 and the laser light emitted from the light irradiation unit 13. The amount of light is compared in the blood flow rate calculation unit 25, and based on this, the blood flow rate in the shallow portion 42 is calculated.

  Therefore, the control unit 22 can change the light irradiation conditions such as the peak intensity of light generated in the light source 21 and the repetition frequency in real time based on the detected photosensitive substance or oxygen concentration.

  The conditions of the laser beam and PDT drug used in this embodiment will be described.

  The wavelength of the laser light applied to the lesioned part 41 is 600 nm to 800 nm, and a light beam having a wavelength close to the absorption wavelength of the PDT drug to be used may be used. In particular, a laser beam generated by a wavelength-tunable optical parametric oscillator (OPO) is desirable. The wavelength of the light generated by OPO can be changed, and the lesion can be widely treated from the shallow to the deep by changing the wavelength and the irradiation peak intensity of the light.

  The shallow part 42 in the lesion part 41 to be adjusted is, for example, about 0.05 mm to 10 mm, and the deep part is a part deeper than that.

The laser light irradiation conditions can be appropriately determined according to the size of the lesion, the type of light used, the PDT drug, and the like. When performing PDT treatment by irradiating a light beam, the pulse energy density (irradiation amount, J / cm ² ) is important, but is obtained by multiplying the peak intensity of the light beam and the pulse width. That is, pulse energy density = peak intensity × pulse width.

In the peak intensity of the irradiated light, the range of the high peak intensity and the range of the low peak intensity are not limited, and can be determined as appropriate depending on the type of the light, the depth of the lesion to be treated, and the like. For example, the peak intensity of the irradiated light may be in the range of 100 mW / cm ^{2 to 5} MW / cm ² , and the total energy density may be ²⁰ to 500 J / cm ² or more. Examples of the peak intensity of the light having a high peak intensity include a range of 10 kW / cm ² or more to a threshold value or less at which plasma starts to be generated on the living body surface by pulse irradiation. Preferably, the peak intensity of the light with high peak intensity is in the range of 100 kW / cm ^{2 to} 10 Mw / cm ² . More preferably, the peak intensity of the light having a high peak intensity is in the range of 200 kW / cm ^{2 to 5} Mw / cm ² .

  In the laser-irradiated portion, it takes a certain time for the locally consumed oxygen to be diffused and supplied from the surrounding tissue. Therefore, it is necessary to match the laser irradiation timing with the oxygen supply. The repetition frequency of such irradiation laser is preferably about 1 Hz to 1 kHz.

  However, the range of high peak intensity and low peak intensity is used both when irradiating with a light irradiation unit set near the lesioned part and when irradiating light from outside the body using a device having a catheter as described later. Therefore, in this case, for example, when a PDT drug is irradiated to a lesion part where the PDT drug is accumulated from a shallow part to a deep part, a light beam having a peak intensity capable of damaging a shallow part of about 0.05 mm to 10 mm from the surface. Is called a low peak intensity light beam, and a peak intensity light beam capable of damaging deeper than that is called a high peak intensity light beam.

  A PDT drug currently used for PDT treatment in practical use is porfimer sodium (PHE) having an absorption wavelength of 630 nm, and is used in combination with an excimer dye laser having a wavelength of 630 nm. However, the excimer dye laser light is limited to the treatment of superficial cancer because it has a depth of about 2 to 3 mm in living tissue.

  The device of the present invention also uses a long-wavelength laser with greater depth of penetration because it also allows treatment of deep lesions that are not possible with current PDT. Therefore, the PDT drug to be used can be any drug having an absorption wavelength near 630 nm to a drug having an absorption wavelength on the longer wavelength side. Among these, a drug having an absorption wavelength at 650 nm to 800 nm is desirable. For example, tarporphine (trade name of Meiji Seika Co., Ltd .: Rezaphyrin) (664 nm) (mono-L-aspartyl chlorin e6, Japanese Patent No. 2961074), ATH-S10 (670 nm) which is a mTHPC (652 nm) chlorin-based drug ( Iminochlorin aspartic acid derivative, Toyo Hakken Kogyo Co., Ltd., Japanese Patent Laid-Open No. 6-80671, SnET2 (660 nm) (tin etiopurpurin, Mirabant Medical Technologies), AlPcS (675 nm) (chloroaluminumsulphine 690nm) (benzoporphyrin derivative monoacid) ring A, QLT), Lu-tex (732 nm) (Lutetium Texaphyrin) and the like (common names, absorption “peak” wavelengths are shown, and general names, sources, and literature are shown).

  Moreover, you may mix and use these chemical | medical agents. By accumulating a plurality of drugs having different absorption wavelengths in the lesion, it is possible to treat not only the wavelength of light and the repetition frequency but also the intensity of irradiation peak, so that the lesion can be treated widely from shallow to deep.

  For administration of these drugs, the drug is dissolved in an appropriate buffer solution such as a phosphate buffer salt solution, and pharmaceutically acceptable additives are added as necessary. Examples of additives include solubilizing agents such as organic solvents, pH adjusters such as acids and bases, stabilizers such as ascorbic acid, excipients such as glucose, and isotonic agents such as sodium chloride.

  The administration method is not limited to a special one. It can be administered by intravenous injection, intramuscular injection, subcutaneous injection, oral administration and the like. The dosage is 0.01 to 100 mg / kg body weight, preferably 1 to 5 mg / kg body weight when administered systemically by intravenous injection or the like. In the case of local administration, for example, a drug prepared to several μg / ml to several mg / ml may be administered by injection or the like directly into the lesioned part by several μl to several ml.

  Next, the operation of this embodiment will be described.

  FIG. 6 is a flowchart showing the flow of the operation of the present embodiment, FIG. 7 is a schematic diagram showing a state in which a lung tumor is treated as a lesion by way of example using a catheter, and FIGS. ) Is a schematic cross-sectional view showing the treatment state at the catheter tip in stages. In FIG. 8A, white circles represent alveoli, and black masses represent lung cancer tumor tissues that are the lesions 41. The black mass has changed to a white mass, indicating that treatment has been completed.

  In the stage of the start of treatment shown in FIG. 6, the PDT drug has already been administered to the patient, is sufficiently diffused to the light irradiation site including the lesioned portion 41, and the light irradiation unit 13 is disposed at an appropriate irradiation position. .

  First, initial treatment conditions are input to the control unit 22 (step S1). The initial treatment conditions are the peak intensity, frequency, total administration energy, concentration of the PDT drug supplied to the living body 40, or the area to be irradiated with light, the distance to the area to be irradiated with light, Such as irradiation time. These conditions are determined based on the situation obtained by examining the living body 40 in advance, for example, the position of the lesioned part 41 and the like. Specifically, the depth of the lesioned part 41 is measured, and the initial peak of the pulsed light irradiated by the light irradiating unit 13 so that the peak intensity of the pulsed laser light in the lesioned part 41 falls within a predetermined range for activating the PDT drug. The strength is determined.

  After a predetermined time (about 1 hour) has passed after injecting the PDT drug, the guiding catheter 33 is inserted with the endobronchial tube 32 inserted into the bronchus as shown in FIG. The treatment catheter 10 is inserted using as a guide. And the treatment catheter 10 protrudes from the front-end | tip of the guiding catheter 33, and it inserts to the very bronchiolopulmonary lungs in the lesioned part 41 vicinity (state shown to FIG. 8A).

  In this embodiment, it is not necessary to wait until the PDT drug is absorbed and accumulated in the lesioned part 41, and the treatment can be started after about one hour has elapsed after the PDT drug has been injected. This is because in the PDT according to the present invention, it is considered that the PDT drug supplied by the blood flow has a greater influence on the treatment result than the PDT drug taken into the cells.

  Therefore, as in the conventional normal PDT, in a dark place where no visible light hits for a long time (about 48 hours) until the difference in concentration of the PDT drug occurs between the target lesion cell such as a cancer tumor and the surrounding healthy cells. There is no need to wait, and the physical and mental burden on the patient is greatly reduced, which is a great merit for medical professionals and high in terms of medical economy.

  Moreover, the treatment catheter 10 does not need to penetrate into the lesioned part 41, and may be in a state of being disposed at a position about 0.5 to 1 cm away from the lesioned part 41. Therefore, for example, there is no risk of cancer cells adhering to the treatment catheter 10, and even when the treatment catheter 10 is removed after treatment, there is no risk of causing cancer cells to move to the path and causing cancer metastasis.

  Based on the initial treatment conditions, the control unit 22 operates the light source 21 to start irradiation with high-intensity pulsed laser light from the light irradiation unit 13 toward the lesion site (step S2).

  At the stage where 20 seconds have elapsed from the start of irradiation with the high-intensity pulsed laser light, the detection means 23 monitors the blood flow in the shallow portion 42 of the lesioned part 41 and determines the blood flow rate at the surface of the living body (step S3). In the present embodiment, the blood flow amount calculation unit 25 compares the light amount of the irradiated laser light and the light amount of the return light detected by the sensor 26, and determines the blood flow amount on the surface portion of the living body based on the calculation result. .

  If the blood flow is confirmed in the shallow portion 42 to be preserved by the determination (step S4: YES), the PDT drug is activated in the shallow portion 42 of the lesioned portion 41 by irradiation with the pulse laser beam, There is a possibility that the cells are damaged, and the intensity of the pulsed laser beam is increased because the intensity of the pulsed laser beam is insufficient (step S5). On the other hand, when blood flow is not confirmed, irradiation with pulsed laser light does not activate the PDT drug in the shallow part 42 of the lesioned part 41, and there is no risk of cell injury, and irradiation with normal pulsed laser light. Therefore, the intensity of the pulse laser beam is maintained (step S6: NO).

  When the high-intensity pulsed laser beam is irradiated in this manner, the PDT drug is activated in the lesioned part 41, and the cells of the lesioned part 41 are damaged by the mechanism described above.

  However, a high-intensity pulse laser beam and a low-intensity pulse laser beam can be used in combination as appropriate. FIG. 8B shows a state where a deep part treatment is performed by irradiation with a high-intensity pulsed laser beam, and FIG. 8C shows a case where a shallow part 42 is treated by irradiation with a low-intensity pulsed laser beam. Show the state.

  When irradiated with high-intensity pulsed laser light, the blood flow in the tissue near the light emitting part (shallow part 42) is reduced by the high-intensity pulsed laser light, and no therapeutic effect is obtained. A therapeutic effect is obtained for the tissue far away from the emission part (deep part). The treatment depth is, for example, 1 to 3 cm, and as shown in FIG. 8 (B), a bulbous region having a diameter of about 6 cm is treated.

  When the low-intensity pulsed laser beam or continuous light (CW irradiation) is used subsequently to the above-described high-intensity pulsed laser beam, the structure of the shallow part 42 left after the treatment in the vicinity of the light emitting part (shallow part 42) is illustrated. It can be treated as shown in 8 (C).

Finally, the control unit 22 determines whether or not the treatment is completed based on the initial treatment conditions such as the treatment time (step S7). If the treatment has not ended (step S7: NO), the processing from step S2 is repeated. When treatment has been completed (step S7)
: YES), photodynamic therapy is terminated.

  Thus, in the PDT according to the present embodiment, the shallow part can be preserved and only the deeply affected part can be treated.

  For example, when primary lung cancer is found in the periphery of the lung, common surgical operations also remove lymph nodes that are suspected of metastasis. At this time, it is not possible to remove only the lymph node, but the entire lung tissue and bronchi are cut off. If the lungs are severely cut, the ability to ventilate is greatly impaired, breathing becomes difficult, and the quality of life of the patient after treatment is significantly reduced.

  Moreover, in normal PDT in which superficial preservation is impossible, the cancer tumor formed in the airway mucosa is treated from the inside. The bronchus is composed of airway mucosa, airway wall, bronchial cartilage and the like from the inside, and the lymph node is on the outside. When the treatment depth is increased with normal PDT and treatment is performed up to the lymph node, the bronchial structure is destroyed. After treatment, edema occurs, causing problems such as respiratory stenosis and difficulty in breathing.

However, in the PDT according to the present embodiment, there is no possibility of such a problem, and only the lesioned part 41 in the deep part can be treated while the shallow part is reliably preserved.
(Second Embodiment)
In the above-described embodiment, the light irradiation unit 13 irradiates the laser beam and detects the reflected light from the living body 40. In the present embodiment, the blood flow rate is detected based on the temperature of the living body 40. It is. When the blood flow is reduced by irradiating laser light, the temperature of the living body 40 also changes. Therefore, when the temperature of the living body 40 before the irradiation with the laser light and the temperature of the living body 40 after the irradiation are measured and compared in the control unit 22, the blood flow rate in the shallow living body 42 can be detected.

  FIG. 9 is a block diagram according to the second embodiment, FIG. 10 is a graph showing the temperature measurement results near the living body surface and the deep part of the living body at the time of laser light irradiation, and FIG. (B) shows the case of low-intensity pulsed laser light irradiation. In the graph, the thin line represents the temperature change in the shallow tumor portion 42, and the thick line represents the temperature change in the deep tumor portion. In addition, the same code | symbol is attached | subjected to the member which is common in the member shown to a previous figure, and description is abbreviate | omitted.

  First, it verified by experiment about the point that the temperature of the biological body 40 also changes, when blood flow volume reduces by irradiating a laser beam. The experiment was a mouse InVIVO experiment, and a thermocouple was punctured into the living body 40 under treatment, and the temperature was measured. The shallow tumor portion 42 is 200 μm from the surface layer, and the deep tumor portion is 5 mm from the surface layer. The high intensity pulse laser light and the low intensity pulse laser light have the values shown in Table 1 below.

  The experimental results shown in FIGS. 10A and 10B were obtained. As is clear from this experimental result, when irradiated with high-intensity pulsed laser light, the temperature near the surface of the living body rises significantly compared to the depth of the living body, whereas when irradiated with low-intensity pulsed laser light, the difference in temperature difference due to depth is Few. This shows a state where the blood flow is lowered in the shallow part of the living body and the temperature is rapidly increased due to the loss of the tissue cooling effect by the blood flow when the high-intensity pulsed laser beam is irradiated. Therefore, the blood flow rate in the shallow portion 42 can be monitored by measuring the actual temperature of the living body 40.

  As shown in FIG. 9, in the present embodiment, a temperature sensor 27 is provided in the vicinity of the light irradiation unit 13, and a temperature signal on the surface of the living body detected by the temperature sensor 27 is input to the control unit 22.

Therefore, if the temperature change state shown in the graphs of FIGS. 10A and 10B is stored in the control unit 22 in advance and compared with the temperature detected from the living body 40, the blood flow rate of the living body 40 is detected. be able to.
(Third embodiment)
FIG. 11 is a block diagram according to the third embodiment, and members that are the same as those shown in the previous drawings are given the same reference numerals, and descriptions thereof are omitted.

  The detection means 23B according to the present embodiment recognizes the shape of a blood vessel in the direction of the deep part of the living body through image diagnosis using ultrasonic waves or laser light. It is something to be offered.

  In the field of endoscopes, a method of clearly drawing blood vessels using an optical filter is generally known. In the present embodiment using this technique, an endoscope 28 is used as shown in FIG.

  In the detection of the number of blood vessel distributions, first, the light irradiation unit 13 captures an image of the lesioned part 41 with the camera C between the pulses of the pulse laser light irradiation, and the image obtained through the optical filter 29 provided in the endoscope 28. Information is guided to the image acquisition unit (image acquisition unit) 30, and based on the image signal from the image acquisition unit 30, the blood flow rate calculation unit 31 performs an operation for calculating the number of blood vessel distributions in the visual field of the endoscope 44. The obtained value is fed back and input as a control signal to the control unit 22 to control the pulsed light emitted by the light irradiation unit 13.

In this way, the distribution state of blood vessels can be detected from the image of the living body 40, and the blood flow rate in the shallow living body 42 can be detected from the obtained number of blood vessel distributions.
(Fourth embodiment)
In the embodiment described above, in detecting the blood flow rate in the shallow portion 42 of the living body 40, the return light, the temperature change of the living body 40, and the number of blood vessel distributions by image diagnosis are used. Or a blood flow rate detected by optical Doppler shift.

  First, what detects a color tone will be described. When the blood flow is reduced by irradiating laser light, the amount of blood color signal in the image signal of image diagnosis also changes, so if you measure the change in the amount of blood color signal before and after laser light irradiation, The blood flow can be grasped.

  That is, for example, if the temperature sensor 27 shown in FIG. 9 is a color sensing sensor, the red amount of blood before laser light irradiation and the red amount of return light are measured and compared in the control unit 22, The blood flow rate in the living body shallow part 42 can be detected.

  What is detected by optical Doppler shift will be described. Since the return light described above changes the frequency of the light according to the blood flow in the living tissue, the blood flow can be grasped by measuring the amount of change in the frequency of the return light.

  That is, for example, if the temperature sensor 27 shown in FIG. 9 is a sensor that detects a frequency, and the frequency of the laser light emitted from the light irradiation unit 13 is compared with the frequency of the return light detected by the sensor, the living body The blood flow volume in the shallow portion 42 can be detected. However, the measurement is preferably performed while the blood vessel cross-sectional area does not change. When the blood vessel cross-sectional area changes, it becomes difficult to grasp the blood flow rate, that is, the blood volume.

  In the embodiment described above, the present invention is applied to the treatment of the lung. However, the application of the present invention is not limited to the lung and bronchus, and the urethra, blood vessel, intestinal tract, nasal cavity, oral cavity, ear canal, vagina, and the like. The present invention can also be applied to the treatment of a living body lumen or an organ without a lumen.

  In addition, the lesion to be treated by the laser irradiation apparatus of the present invention is a disease lesion associated with abnormal cell proliferation or atheroma in the tissue, and the progression of the disease is stopped by damaging the tissue lesion. It is a lesion that can be treated and prevented from spreading. Examples of the disease having such a lesion include carcinoma, sarcoma, benign tumor, arteriosclerosis accompanied by atheroma. There is no limitation on the site of occurrence of these diseases, and there is no limitation on the degree of progression. For example, in the case of a carcinoma, the target is from superficial early cancer to invasive advanced cancer. Among these, a disease in which a lesion is present up to a deep tissue is preferable, and a disease in which a normal part covers the lesion is preferable.

  The normal part that covers the affected part is not necessarily the same tissue as the affected part. When an attempt is made to irradiate the affected part with light using the device of the present invention, there are other tissues in the affected part and the irradiated part. This includes cases where

  Such diseases include carcinomas in the epithelium with normal epithelial surface, non-epithelial cells (stromal cells: cells that constitute the supporting tissue) sarcoma that exist within the tissue, and epithelial When the light irradiation part of the device is inserted into the urethra, such as sarcoma covered with cells, prostate cancer or benign prostatic hyperplasia, the normal part (urethral wall) between the lesion part (prostate) and the light irradiation part When there is a light irradiation part of the device inserted into the artery, such as atherosclerosis, there is a normal part that covers the lesion part (the atheroma) between the lesion part (the atheroma) and the light irradiation part Examples of the disease include (film).

  In the above-described embodiment, only the PDT drug is used at the time of photodynamic therapy. However, the therapeutic effect can be obtained by administering a drug having an effect on the blood flow, for example, a thrombolytic agent (such as aspirin). It is expected to improve. When a drug having an effect on blood flow is administered, vascular occlusion at the treatment site is hindered and the treatment effect can be improved.

  Examples of vasoactive agents include the following.

  (1) At the time of PDT treatment, for example, if a drug having the following antithrombotic medicinal properties is used in combination, improvement of therapeutic effects such as thrombus, embolism, blood flow disorder and the like can be expected.

Aspirin, ticlopidine hydrochloride, warfarin potassium, heparin sodium, nasalplase, alteplase, urokinase, tisokinase, argatroban Indomethacin, ibuprofen, ketoprofen, naproxen, piroxicam (2) When treating with PDT, for example, if a drug with the following vasodilatory action is used in combination, the increase or decrease in the therapeutic effect of the site where vascular occlusion is prevented cannot be mentioned, It may have the effect of maintaining the supply of drug and oxygen to the lesion site while pulsed laser light irradiation continues.

Trazoline hydrochloride, cilostazol, beraprost sodium, bamethane sulfate, fasudil hydrochloride As described in the part explained as the premise of the present invention, the vasoconstrictive action, which is a feature of the present invention, is caused by stimulation caused by singlet oxygen generated and There are three factors, i.e., stimulation by intense pulsed light and thermal stimulation produced by high-intensity pulsed light. Therefore, various drugs such as porphyrin derivatives and crawlin substances have been proposed as PDT drugs. For example, as porphyrin derivatives, there are JP-A-9-124652, WO98 / 14453, JP-A-4-330013, Japanese Patent No. 2961074, etc., for various cancers as target diseases for photochemical treatment. Are Japanese Patent Publication No. 7-53733, Japanese Patent Laid-Open No. 9-124652, etc., and for autoimmune diseases, there are WO 99/07364, WO 98/19677, WO 98/14453, As for arteriosclerosis, Japanese Patent No. 3154742, WO00 / 59505 and the like have been reported.

  However, the stimulation described above occurs in any drug, and the treatment according to the present invention can be performed.

  The present invention will be specifically described by the following examples, but the present invention is not limited to these examples.

  FIG. 12 is a schematic cross-sectional view showing a state in which lung cancer of a mouse is treated using a catheter.

For example, when the lesioned part 41 is in the peripheral part of the lung, PDT is performed using the therapeutic catheter 10. As an initial treatment condition, the peak intensity of a pulsed laser beam having a wavelength of 664 nm is 10 mJ / cm ² , the repetition frequency is 10 Hz, and the total administration energy is 100 J / cm ^2. The photosensitizer resaphyrin was injected at a concentration of 2 mg / kg.

  As the light source, an excimer die laser (EDL-1, Hamamatsu Photonics) was used. Oosazine 740 concentration 0.5 mM was added to rhodamine 640 concentration 0.5 mM (solvent ethanol), and it was used as a light source having an oscillation wavelength of 667 ± 3 nm and a pulse width of 10 ns by using laser dye degradation.

  After injecting the PDT drug and passing 1 hour, the guiding catheter 33 was inserted with the endobronchial tube 32 inserted into the bronchi. The treatment catheter 10 was inserted using the guiding catheter 33 as a guide, and the treatment catheter 10 was projected from the distal end of the guiding catheter 33 to reach the bronchi near the lesioned portion 41.

The control unit 22 was operated, and high intensity pulsed light having a light peak intensity of 10 mJ / cm ² was irradiated from the light irradiation unit 13 toward the lesion site at an irradiation region diameter of 8 mm at 100 J / cm ² .

  48 hours after the implementation, the PDT effect was verified. The verification was judged by observing an HE-stained image after thinly slicing the tumor and fixing it with formalin. As for the shallow part 42, the preservation | save site | part of thickness 0.3mm-0.5mm was confirmed, the treatment depth to the deep part depth 5mm was able to be obtained, and it has confirmed that the lesioned part 41 was killed.

  The present invention makes it possible to treat only a deeply affected part while preserving the shallow skin film, which is a healthy part of a living body, without damaging it.

It is the schematic which shows the experimental result regarding the shallow part preservation mechanism by irradiation of a high intensity | strength pulsed laser beam with time. 1 is a schematic perspective view of a photodynamic therapy device according to a first embodiment. It is a block diagram which shows schematic structure of the photodynamic treatment apparatus. It is a front view of a catheter. (A)-(D) are front views which show the front-end | tip part of a catheter. It is a flowchart which shows the flow of operation | movement of 1st Embodiment. It is the schematic which shows the state which is treating the tumor of a lung as a lesioned part using a catheter. (A)-(D) are schematic sectional drawings which show the treatment state in a catheter front-end | tip part in steps. It is a block diagram concerning a 2nd embodiment. A graph showing the temperature measurement results near the living body surface and in the deep part of the living body at the time of pulse irradiation, (A) shows the result when irradiated with high-intensity pulsed laser light, and (B) shows the result when irradiated with low-intensity pulsed laser light. Show. It is a block diagram concerning a 3rd embodiment. It is a schematic sectional drawing which shows the state which is treating the lung cancer of a mouse | mouth using a catheter.

Explanation of symbols

1 ... Photodynamic therapy device,
10 ... treatment catheter,
11 ... Irradiation means,
13 ... light irradiation part,
20 ... Irradiation control means,
21 ... light source,
22 ... control unit,
23. Detection means,
24: Optical branching section,
25. Blood flow calculation means,
40 ... living body,
41 ... lesions,
42 ... Shallow part,
F: Optical fiber,
M ₁ , M ₂ ... markers.

Claims (6)

A photodynamic therapy device for treating a lesion in a deep part of a living body using a photosensitive substance activated by light,
Irradiating means for irradiating the lesion with light that activates the photosensitive substance;
Irradiation control means for controlling the peak intensity of the light so as to reduce the amount of blood flowing through the shallow blood vessel on the irradiation means side of the lesioned part ,
The irradiation control means includes a detection means for detecting a blood flow volume in the shallow portion, and the light emitted by the irradiation means so as to adjust a contraction of the blood vessel in the shallow portion based on a detection result of the detection means. And a control means for controlling the peak intensity of the photodynamic therapy device. The detection means measures the light quantity of the return light, the light branching part for separating the light emitted by the irradiation means and the return light reflected from the living body, and determines the blood quantity from the return light quantity. The photodynamic therapy device according to claim 1 , further comprising a blood flow rate calculation means for calculating a flow rate . The detection means is an image acquisition means for acquiring the image of the shallow portion, and a blood flow rate calculation means for calculating a blood flow rate based on a ratio of a color tone corresponding to blood in the image or the number of blood vessels included in the image. And a photodynamic therapy device according to claim 1 or 2. The control means measures a predetermined time and controls the peak intensity of the light emitted by the irradiating means so that the blood flow after the predetermined time is equal to or less than the blood flow before the predetermined time. The photodynamic therapy apparatus in any one of 1-3 . The control means reduces the amount of blood flowing through the shallow blood vessel immediately after the start of light irradiation until the initial blood flow suppression time, and after the initial blood flow suppression time has elapsed until the end of light irradiation. The peak intensity of the light is controlled so as to maintain the contraction of the shallow blood vessel.
Item 4. The photodynamic therapy device according to any one of Items 1 to 3 . The light-sensitive substance is activated by light having a peak intensity in a predetermined range, and has a characteristic that it is difficult to activate by light having a peak intensity outside the predetermined range. Photodynamic therapy device.

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