Cancer treatment devices

Abstract

To provide a topical and low invasive cancer treatment.SOLUTION: A cancer treatment apparatus includes an endoscope, a deep ultraviolet ray source for emitting a deep ultraviolet ray having a peak wavelength in 200-300 nm, and a deep ultraviolet ray irradiation probe having an optical fiber guide connected to the deep ultraviolet ray source for propagating the deep ultraviolet ray emitted from the deep ultraviolet ray source, and emitting it from the emission end part. The deep ultraviolet ray irradiation probe is arranged so as to freely move back and forth in an axial direction of an insertion part of the endoscope. The emission end part of the optical fiber guide is positioned at the tip of the insertion part.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] The present invention relates to a cancer treatment device that utilizes deep ultraviolet light. [Background technology]

[0002] In cancer treatment by radiation therapy or chemotherapy, induction of cancer cell death by DNA damage is utilized. However, radiation therapy from the body surface irradiates cells other than cancer cells with radiation. In addition, even with systemic administration of anticancer drugs, it is inevitable that radiation will affect non-cancer tissues or non-cancer cells other than the cancer site. Therefore, drug delivery systems that can locally irradiate cancer and administer anticancer drugs are being investigated.

[0003] Regarding the application of ultraviolet light in the medical field, a method has been disclosed in which the stomach is photographed with ultraviolet light and the irregularities of the stomach surface are exaggerated in the gastroscope image (see Non-Patent Document 1). It has also been disclosed that deep ultraviolet light is easily absorbed by DNA, and that deep ultraviolet light induces the inactivation of bacteria through DNA damage (see Non-Patent Document 2), and that a method of treating inflammatory bowel disease by irradiating the body with UV-A or UV-B (see Patent Document 1) has been disclosed. However, deep ultraviolet light is difficult to handle because it is considered to be a risk factor for skin cancer, and the application of deep ultraviolet light to treatment has not progressed at present.

[0004] Therefore, in the treatment of cancer, particularly stomach cancer, endoscopic resection is widely used, in which the inside of the body cavity is observed using an endoscope while the cancerous area is resected. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Special Publication No. 2019-517305 [Non-patent literature]

[0006] [Non-Patent Document 1] Hirofumi Niwa Gastroenterological Endoscopy Vol 53(2), Feb.2011 [Non-Patent Document 2] Takagi et al., Lasers in Medical Science, DOI: 10.1007 / s10103-020-03143-7, September 2020 Summary of the Invention [Problem to be solved by the invention]

[0007] In cancer treatment, it is desirable to treat the cancer as locally as possible. Therefore, an object of the present invention is to provide a localized and minimally invasive cancer treatment. [Means for solving the problem]

[0008] In a previous study, the inventors of the present invention obtained experimental results showing that various bacteria were killed in vitro by DNA damage caused by deep ultraviolet rays. Therefore, thinking that deep ultraviolet rays could be used to kill cancer cells, they irradiated cancer cells with deep ultraviolet rays having a specific wavelength peak, and found that cancer cell death was induced by DNA damage, thus completing the present invention.

[0009] That is, the present invention is as follows. [Claim 1] An endoscope, a deep ultraviolet light source unit that emits deep ultraviolet light having a peak wavelength of 200 to 300 nm, and a deep ultraviolet light irradiation probe having an optical fiber guide that is connected to the deep ultraviolet light source unit and propagates the deep ultraviolet light emitted from the deep ultraviolet light source and emits it from an emission end, A cancer treatment device, characterized in that the deep ultraviolet ray irradiation probe is arranged so as to be freely advanced and retreated in the axial direction of an insertion part of an endoscope, and the emission end part of the optical fiber guide is located at the tip of the insertion part. [Claim 2] The cancer treatment device according to [1] above, characterized in that the endoscope is provided with a treatment instrument channel or a guide tube, and the deep ultraviolet ray irradiation probe is inserted into the treatment instrument channel or the guide tube. [Claim 3] The cancer treatment device according to the above-mentioned [2], wherein the diameter of the optical fiber guide is 0.3 to 0.95 times the diameter of the treatment instrument channel or the guide tube. [Claim 4] The cancer treatment device according to any one of the above [1] to [3], wherein the light source in the light source section is a light emitting diode. [Claim 5] The cancer treatment device according to any one of the above [1] to [4], wherein the peak wavelength of the deep ultraviolet light is 260 to 285 nm.

[0010] In another aspect of the present invention, there is provided a method for treating cancer by irradiating cancer cells in a body cavity with deep ultraviolet light, the method comprising: (a1) inserting an endoscope having a deep ultraviolet light source unit that emits deep ultraviolet light having a peak wavelength of 200 to 300 nm, and a deep ultraviolet light irradiation probe that is connected to the deep ultraviolet light source unit and has an optical fiber guide that propagates the deep ultraviolet light emitted from the light source and emits it from an emission end, through the mouth, nose, or anus, and allowing the tip of the endoscope to reach the vicinity of cancer cells in the body cavity; and (b1) emitting deep ultraviolet light having a peak wavelength of 200 to 300 nm from the emission end. [2] A method for treating cancer in a body cavity, on the skin, or in the oral cavity, comprising: (a2) a deep ultraviolet light source unit that emits deep ultraviolet light having a peak wavelength of 200 to 300 nm; and a step of connecting the deep ultraviolet light source unit to the deep ultraviolet light source unit, and a step of bringing an emission end of a deep ultraviolet light irradiation probe having an optical fiber guide that propagates the deep ultraviolet light emitted from the light source and emits it from the emission end, to the vicinity of cancer cells in a body cavity, on the skin, or in the oral cavity; and (b2) a step of emitting deep ultraviolet light having a peak wavelength of 200 to 300 nm from the emission end. Effect of the Invention

[0011] The cancer treatment device of the present invention makes it possible to treat cancer, particularly gastric cancer, in a minimally invasive manner. [Brief description of the drawings]

[0012] [Figure 1] FIG. 2 is a diagram showing the wavelength characteristics of deep ultraviolet light irradiated in Example 1 with a peak wavelength of 265 nm. [Diagram 2] 1 shows the results of phase-contrast microscopy (magnification ×10) for evaluating cell morphology 48 hours after irradiation with deep ultraviolet light in Example 1. The right side shows NCC24 cells, and the left side shows YCCEL1 cells. [Diagram 3] 3 shows the results of observing cell morphology with a phase contrast microscope 48 hours after irradiation with deep ultraviolet rays or ultraviolet rays in Example 1 (magnification ×10). Fig. 3(a) shows the results without irradiation, (b) shows the results with irradiation with deep ultraviolet rays, and (c) shows the results with ultraviolet rays. [Figure 4] 1 is a graph showing the results of evaluating the number of viable cells (YCCEL1 cells) 48 hours after irradiation with deep ultraviolet rays or ultraviolet rays, assuming the number of viable cells in a non-irradiated control to be 100 in Example 1. [Diagram 5] 1 is a diagram showing an outline of one embodiment of a deep ultraviolet irradiation device of the present invention. [Figure 6] FIG. 2 is an enlarged perspective view of a tip portion of an endoscope insertion part of the deep ultraviolet irradiation device of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] The cancer treatment device of the present invention is not particularly limited as long as it is a device (hereinafter also referred to as "the present cancer treatment device") that includes an endoscope, a deep ultraviolet light source unit that emits deep ultraviolet light having a peak wavelength of 200 to 300 nm, and a deep ultraviolet irradiation probe connected to the deep ultraviolet light source unit and having an optical fiber guide that propagates the deep ultraviolet light emitted from the deep ultraviolet light source and emits it from an emission end, wherein the deep ultraviolet irradiation probe is arranged to be able to move forward and backward in the axial direction of the insertion part of the endoscope, and the emission end of the optical fiber guide is located at the tip of the insertion part, and such a cancer treatment device can locally kill cancer cells.

[0014] <Endoscope> The endoscope in this specification includes an insertion section inserted from the nose, mouth, anus, etc. of the subject, and an operation section provided with an angle knob, and the operation section is connected to a connector section. The connector section is further connected to a monitor, a camera signal processing device, and an illumination light source generating device. The insertion section is provided with a treatment tool channel or a guide tube, and an optical fiber guide that transmits deep ultraviolet light is arranged so as to be able to move forward and backward in the axial direction of the insertion section of the endoscope. When the insertion section is provided with a treatment tool channel, an optical fiber guide is inserted from a treatment tool insertion port provided between the operation section and the insertion section through a hollow treatment tool channel in the insertion section to a treatment tool outlet at the tip of the insertion section. On the other hand, when the insertion section is provided with a guide tube, such a guide tube is provided on the outer surface of the insertion section, and an optical fiber guide is inserted into the guide tube.

[0015] Furthermore, an illumination optical fiber guide for illuminating the inside of the body cavity is inserted into the inside or outer surface of the insertion portion, with the emission end of the illumination optical fiber guide being located at the tip of the insertion portion and the base end of the illumination optical fiber guide being connected to the connector portion.

[0016] The light emitted from the illumination light source generating device is transmitted through the illumination optical fiber guide and is emitted from the emission end of the illumination optical fiber guide, illuminating the inside of the body cavity and making it easier for the operator to identify cancer within the body cavity. Examples of such light sources include light emitting diodes (LEDs), xenon lamps, halogen lamps, lasers, and mercury lamps.

[0017] Furthermore, a camera is attached to the tip of the insertion part to capture images inside the body cavity, and the image signal captured by the camera is sent to a camera signal processor via the connector, after which the image is displayed on a monitor. The operator can identify the cancer site and perform cancer treatment with deep ultraviolet light while observing the inside of the body cavity displayed on the monitor.

[0018] Furthermore, at the tip of the insertion portion, in addition to the emission end of the illumination optical fiber guide, a treatment tool outlet which is one end of the treatment tool channel and / or the tip of the guide tube are located.

[0019] The angle knob of the operation unit can be rotated to adjust the tip of the insertion unit to any angle. In addition, a switch for taking images, a suction button, and an air supply button may be provided as necessary.

[0020] At least the tip of the insertion part is made of a flexible material, and can be bent freely at a specified angle upward, downward, leftward, or rightward by operating the angle knob. By bending the tip of the insertion part toward the cancer cells to be treated, the operator can irradiate deep ultraviolet light only to the area where the cancer cells to be treated are present or in the vicinity thereof.

[0021] <Deep UV irradiation probe> The deep ultraviolet irradiation probe is equipped with a deep ultraviolet light source and an optical fiber guide. The deep ultraviolet light in this specification is not particularly limited as long as it has a peak wavelength of 200 to 300 nm, but is preferably a deep ultraviolet light having a peak wavelength of 220 to 290 nm, more preferably 250 to 285 nm, and even more preferably 265 nm or 280 nm. The full width at half maximum of the deep ultraviolet light emission spectrum can be, for example, 30 nm or less, preferably 25 nm or less, and more preferably 20 nm or less. Furthermore, a filter that cuts a predetermined wavelength may be provided so that only deep ultraviolet light having a wavelength near the peak wavelength is irradiated.

[0022] The optical fiber guide of the deep ultraviolet irradiation probe is disposed so as to be freely advanced and retreated in the axial direction through the treatment tool channel of the endoscope, and is freely attachable and detachable. The emission end of the optical fiber guide is located at the tip of the endoscope. Here, "located at the tip" means that the emission end of the optical fiber guide is in the vicinity of the tip of the endoscope and a predetermined deep ultraviolet ray is emitted from the emission end, and the emission end may protrude from the tip surface of the endoscope, the tip surface of the endoscope and the tip surface of the emission end may be flush with each other, or the emission end may be recessed inside the endoscope relative to the tip surface of the endoscope.

[0023] The deep ultraviolet light source unit in this specification includes a light source that emits deep ultraviolet light, and a light source control unit that controls the light source. The irradiation of deep ultraviolet light can be controlled by turning the power on and off. The irradiation time of deep ultraviolet light may be controlled by turning the power on and off, but an irradiation control unit may be provided in which the irradiation time is input in advance and irradiation is performed for a set time using an irradiation switch. Examples of light sources include, but are not limited to, LEDs, xenon lamps, halogen lamps, lasers, and mercury lamps. A power supply source and a light source switch are connected to the deep ultraviolet light source unit, and the irradiation of deep ultraviolet light can be controlled by the light source switch.

[0024] The light source control unit in this specification controls the light source to emit deep ultraviolet light of a predetermined wavelength at a predetermined intensity.

[0025] <Optical fiber guide> The optical fiber guide in this specification is connected to a deep ultraviolet light source unit, and transmits deep ultraviolet light emitted from the light source and emits it from an emission end. The optical fiber guide may be one in which a plurality of optical fibers are bundled. The optical fiber guide may be one that can be inserted into a treatment instrument channel or a guide tube so as to be able to move forward and backward. The outer diameter may be shorter than the diameter of the treatment instrument channel or the guide tube, and the diameter of the optical fiber guide may be 0.3 to 0.95 times the diameter of the treatment instrument channel or the guide tube, with the lower limit being 0.4 times, 0.5The diameter of the optical fiber guide may be 0.5, 0.6, or 0.8, with the upper limit being 0.9, 0.85, or 0.8. When an endoscope is used, a bent portion is generated in the insertion portion. Therefore, by setting the diameter of the optical fiber guide to the above range, the optical fiber guide comes into contact with at least the bent portion of the treatment instrument channel or the guide tube, and as a result, it becomes possible to fix the optical fiber guide to the treatment instrument channel or the guide tube without using a fixing means.

[0026] However, when cancer treatment is performed, the emission end of the optical fiber guide may be fixed near the tip of the endoscope. By fixing the emission end near the tip of the endoscope, it becomes possible to make it easier for the emission end of the optical fiber guide to irradiate deep ultraviolet light in a desired direction, such as a vertical direction, with respect to the surface of the treatment tool outlet at the tip of the endoscope when the insertion part is bent.

[0027] The material of the treatment tool channel or guide tube can be selected from those with hardness that does not prevent bending of the tip of the endoscope. The base end of the optical fiber guide is connected to the optical fiber guide power supply unit. The power supply unit can control the current to the optical fiber guide, and the deep ultraviolet light emission can be turned on and off by the deep ultraviolet light switch. The other end of the optical fiber guide can also emit deep ultraviolet light, making it possible to locally irradiate the cancer with deep ultraviolet light.

[0028] <Cancer treatment> By using this cancer treatment device, it becomes possible to treat cancer in a minimally invasive manner. A specific cancer treatment method will be described using the case of treating stomach cancer using this cancer treatment device as an example, but it can also be used to treat cancers other than stomach cancer, such as colon cancer, esophageal cancer, pharyngeal cancer, laryngeal cancer, bile duct cancer, and oral cancer.

[0029] The insertion part of the endoscope is inserted through the mouth, nose, anus, etc., so that the tip of the insertion part reaches the specified lumen. The operator observes the surface of the lumen while watching the image captured by the camera at the tip on the monitor, and judges whether or not there is cancer. If cancer is found, the angle knob is operated so that the exit end of the optical fiber guide is positioned 0.2 to 3 cm away from the surface of the cancerous area, and deep ultraviolet light is irradiated for a specified time with a specified light intensity.

[0030] The irradiation time of deep ultraviolet light can be adjusted appropriately depending on the area, depth, etc. of the cancerous area to be irradiated, and can be 1 to 180 seconds per treatment, with the lower limit being 2, 3, 5, 8, 10, 15, or 20 seconds and the upper limit being 150, 120, 90, or 80 seconds, and irradiation can be performed once or in two or more separate treatments.

[0031] The present invention will be described in more detail below with reference to examples. The examples are not limiting.

[0032] [Example 1] Gastric cancer cell lines (YCCEL1, NCC24) were irradiated with deep ultraviolet light or ultraviolet light using a deep ultraviolet light emitting diode with a peak wavelength of 265 nm and an ultraviolet A (UV-A) light emitting diode with a peak wavelength of 365 nm as a control. Gastric cancer cell lines were plated in a 35 mm dish at 2.0 × 10 5 The cells were seeded on about 1 / dish and cultured at 37°C for 3 days to allow the cells to adhere to the dishes. The cells were washed twice with PBS and then irradiated with deep UV rays. After irradiation, 1 mL of PBS was added and the cells were cultured at 37°C. The conditions for irradiation with deep UV rays are as follows. Figure 1 shows the wavelength characteristics of deep UV rays with a peak wavelength of 265 nm. Number of LED light sources: 1 Wavelength: 265nm Power: 2.8W Current: 350mA Distance from the object: 35mm Irradiance: 0.265mW / cm 2 Irradiation time: 0, 10, 20, 30, 40, 50, 60 seconds

[0033] Cell morphology was evaluated using a phase contrast microscope (10x magnification) after 24 and 48 hours of deep UV or UV irradiation. The results of observation 48 hours after deep UV or UV irradiation (irradiation time 60 seconds) are shown in Figures 2 and 3. In Figure 2, the upper row is a photograph taken before deep UV irradiation, and the lower row is a photograph taken 48 hours after deep UV irradiation, with NCC24 cells on the right and YCCEL1 cells on the left. In addition, in Figure 3, the upper row is a photograph taken before YCCEL1 cell irradiation, and the lower row is a photograph taken 48 hours after 365 nm UV irradiation on the right and 48 hours after 265 nm deep UV irradiation on the left.

[0034] As is clear from Figure 2, 48 hours after deep UV irradiation, both gastric cancer cell lines YCCEL1 and NCC24 changed from a dish-like shape to a spherical shape. Although not shown in Figure 2, further observation under a 40x fluorescence microscope revealed that the cell nuclei were fragmented and apoptosis was induced. Furthermore, as is clear from Figure 3, there was no change in cell morphology at 365 nm, making it clear that deep UV irradiation is effective in preventing cell damage.

[0035] Figure 4 shows the results of evaluating the number of live cells (YCCEL1 cells) 48 hours after irradiation, assuming the number of live cells in the non-irradiated control to be 100. When irradiated with 265 nm light, the number of live cells decreased to approximately 20% even with an irradiation time of just 10 seconds, and the number of live cells decreased to approximately 10% with an irradiation time of 30 seconds, and to approximately 8% with an irradiation time of 60 seconds. On the other hand, when irradiated with 365 nm light, the decrease in the number of live cells was more than 70% even with an irradiation time of 60 seconds, making it clear that this is insufficient to kill cancer cells. Furthermore, the fact that the cancer cells are killed even with a short irradiation time can also reduce the impact of deep ultraviolet irradiation on normal cells, leading to the suppression of side effects.

[0036] (Deep ultraviolet irradiation device) An embodiment of the deep ultraviolet ray irradiation device of the present invention will be described with reference to Fig. 5 and Fig. 6. The deep ultraviolet ray irradiation device 1 comprises an endoscope 2 and a deep ultraviolet ray irradiation probe 3.

[0037] The endoscope 2 includes an insertion section 11, an operation section 12, and a connector section 13, and the operation section 12 is provided with an angle knob 14. The connector section 13 is connected to a base end of an illumination optical fiber guide (not shown), and the illumination optical fiber guide is inserted into the insertion section of the endoscope. The end 15 of the insertion section of the endoscope includes an emission end 16 of the illumination optical fiber guide and a camera 17. The insertion section 11 includes a treatment tool channel 18, which is tubular from a treatment tool channel inlet 19 to a treatment tool channel outlet 20. By operating the angle knob 14, the angle of the end 15 of the insertion section can be bent 210 degrees upward, 90 degrees downward, and 100 degrees left and right. The connector section 13 is connected to a video device with a monitor (not shown), an LED light emitting device, and a power supply. An image from the end of the insertion section is displayed on the monitor. The light emitted by the LED light emitting device is emitted from the emission end 16 of the illumination optical fiber guide via the illumination optical fiber guide.

[0038] The deep ultraviolet irradiation probe 3 includes a deep ultraviolet light source unit 31 and an optical fiber guide 32. The deep ultraviolet light source unit 31 emits deep ultraviolet light D having a peak wavelength at 265 nm, and is connected to the base end of the optical fiber guide 32. The deep ultraviolet light source unit 31 includes a deep ultraviolet light source switch (not shown), and the operator of the endoscope can control on / off of the deep ultraviolet light source and the irradiation time of deep ultraviolet light.

[0039] The optical fiber guide is inserted from the treatment tool channel inlet 19 and is disposed so as to be movable forward and backward in the axial direction within the treatment tool channel 18. The emission end 33 of the optical fiber guide is located at the tip of the insertion portion 11 of the endoscope and irradiates deep ultraviolet light D.

[0040] This device is useful in the treatment of early cancer, especially gastric cancer. When early gastric cancer is limited to the mucosal layer on the surface and the lateral spread of the lesion is 2 cm or less, a method has been established in which the tissue containing the lesion is raised and the tissue containing the lesion is excised. However, in the case of early gastric cancer, especially small lesions with a lateral spread of less than 1 cm, the resection is excessive, and there are many complications such as bleeding or perforation. In the past, the lesion and its surroundings were treated with a laser to kill the cancer cells. However, the laser treatment is dangerous because it affects the deep part of the lesion, and it is no longer used. On the other hand, the device of the present invention can irradiate deep ultraviolet light mainly on the cancer tissue while observing the cancer lesion, making it possible to reduce the impact on normal cells. [Industrial Applicability]

[0041] The cancer treatment device using deep ultraviolet light of the present invention can be used to treat skin lesions where the lesions can be observed from the body surface, and cancers and precancerous lesions in the digestive system, urology, obstetrics and gynecology, and otolaryngology where the lesions can be observed under an endoscope in oral surgery. In addition, by utilizing the bactericidal effect of deep ultraviolet light, it can also be applied in combination with the treatment of infectious diseases or abscesses in these areas. [Explanation of symbols]

[0042] 1...Deep ultraviolet irradiation device 2. Endoscope 3…Deep UV irradiation probe 11...Insertion section 12...Operation unit 13…Connector section 14...Angle knob 15…Tip of insertion part 16...Output end of optical fiber guide for illumination 17…Camera 18...Treatment tool channel 19...Treatment channel inlet 20...Treatment tool channel outlet 31...Deep ultraviolet light source section 32...Fiber optic guide 33...Output end of optical fiber guide D... Deep ultraviolet

Claims

1. An endoscope and A deep ultraviolet light source unit having a light source that emits deep ultraviolet light having a peak wavelength in the range of 200 to 290 nm and a full width at half maximum of an emission spectrum of 20 nm or less, and a deep ultraviolet irradiation probe having an optical fiber guide that is connected to the deep ultraviolet light source unit and propagates the deep ultraviolet light emitted from the light source and emits it from an emission end; Equipped with the optical fiber guide is disposed so as to be movable forward and backward in the axial direction of the insertion portion of the endoscope, and the emission end of the optical fiber guide is located at the tip of the insertion portion, The endoscope is provided with a treatment instrument channel or a guide tube, the optical fiber guide is inserted into the treatment instrument channel or the guide tube, and the diameter of the optical fiber guide is 0.5 to 0.95 times the diameter of the treatment instrument channel or the guide tube.

2. A cancer treatment device as described in claim 1, characterized in that the tip of the insertion part is made of a flexible material and can be freely bent at a predetermined angle in the upward, downward, leftward or rightward directions by operating an angle knob provided on the endoscope.

3. A cancer treatment device as described in claim 1 or 2, characterized in that the light source is a light-emitting diode.

4. A cancer treatment device as described in any one of claims 1 to 3, characterized in that the peak wavelength of the deep ultraviolet light is 260 to 285 nm.

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