Biological body embedding type ultraviolet radiation device and biological body embedding type ultraviolet radiation system

Abstract

To provide a biological body embedding type ultraviolet radiation device capable of performing cancer treatment with reduced side effects such as inflammatory occurrences with low invasion and with a less burden on a patient.SOLUTION: A biological body embedding type ultraviolet radiation device 1 comprises: a power reception coil 2 for receiving wireless power supply; an ultraviolet emission element 6 for emitting ultraviolet by power generated by the power reception coil 2; and a housing 10 for holding the power reception coil 2 and the ultraviolet emission element 6 in a manner where the ultraviolet emitted from the ultraviolet emission element 6 to outside, where the ultraviolet emission element 6 has a peak of an emission wavelength between 300 nm to 400 nm.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a bioimplantable ultraviolet irradiation device that can be used for the treatment of cancer, and a bioimplantable ultraviolet irradiation system using the same. [Background technology]

[0002] The incidence and mortality rates of cancer are still on the rise. Types of cancer with high mortality rates include lung cancer, breast cancer, liver cancer, colon cancer, stomach cancer, and leukemia, and further development of medical technology is required. Cancer treatment methods are mainly broadly classified into chemotherapy using anticancer drugs, radiation therapy using electromagnetic waves or particle beams, surgical procedures such as laparotomy, endoscopic surgery, and laparoscopic surgery, and transplantation procedures such as hematopoietic stem cell transplantation and bone marrow transplantation, but all of them are highly invasive and have side effects, and are also physically burdensome.

[0003] The inventors focused on light energy as a therapeutic method that is minimally invasive, has few side effects, places little physical burden on the body, and is inexpensive, and sought a technology that can highly induce apoptosis (cell death) in cancer cells using light energy while suppressing the induction of necrosis. If it is possible to increase the occurrence of apoptosis (cell death) while suppressing the occurrence of necrosis, it is possible to effectively reduce the number of cancer cells while avoiding the occurrence of inflammation due to cancer treatment. As a result of the inventor's research, it was discovered that by irradiating cancer cells with light in a specific ultraviolet range at an appropriate intensity, it is possible to highly induce apoptosis in cancer cells and suppress the induction of necrosis.

[0004] Although some bioimplantable light irradiation devices have been proposed, such as in Patent Document 1, no proposals that are effective against cancer cells have been made yet. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2019-092532 A Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a bioimplantable ultraviolet irradiation device that enables cancer treatment that is minimally invasive, has few side effects such as inflammation, and places a small burden on the patient. [Means for solving the problem]

[0007] The implantable ultraviolet irradiation device according to aspect 1 of the present invention comprises a receiving coil for receiving wireless power supply, an ultraviolet light-emitting element that emits ultraviolet light using power generated by the receiving coil, and a housing that holds the receiving coil and the ultraviolet light-emitting element in a state in which the ultraviolet light emitted by the ultraviolet light-emitting element can be released to the outside, and is characterized in that the ultraviolet light-emitting element has a peak emission wavelength between 300 nm and 400 nm.

[0008] According to this bioimplantable ultraviolet irradiation device, the bioimplantable ultraviolet irradiation device is implanted in a living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to cancer cells, and power is generated in the power receiving coil by a wireless power supply device from outside the body, and ultraviolet light is generated from the ultraviolet light emitting element using this power to irradiate the cancer cells. This highly induces apoptosis in the cancer cells and suppresses the induction of necrosis, thereby enabling cancer treatment to be performed with minimal invasiveness, fewer side effects such as inflammation, and less of a burden on the patient.

[0009] In the bioimplantable ultraviolet irradiation device according to the second aspect, since the ultraviolet light emitting element is a light emitting diode having an emission wavelength peak between 330 nm and 395 nm, it is possible to effectively induce apoptosis in various cancer cells and suppress the induction of necrosis, thereby enabling cancer treatment that is minimally invasive, has fewer side effects such as inflammation, and places less of a burden on patients. In the experimental results described below, the effectiveness was confirmed for breast cancer, skin cancer, stomach cancer, and leukemia, but since the inventor's experiments have confirmed that cancer cells generally absorb ultraviolet light of specific wavelengths, it can be assumed that the present invention will have a similar effect on any other cancer cells (e.g., colon cancer, esophageal cancer, liver cancer, prostate cancer, uterine cancer, etc.).

[0010] A biological implantable ultraviolet irradiating device according to a third aspect is the device of the first or second aspect, wherein the housing is made of amorphous fluororesin and has a cylindrical shape with both ends sealed. The housing has an outer diameter of 2.9 mm or less.

[0011] The housing is made of amorphous fluororesin and has a cylindrical shape with both ends sealed, so that it can be easily inserted into the living body along the longitudinal direction of the housing, and the housing is highly waterproof, so that the internal structure of the device can be protected for a long period of time. Although amorphous fluororesin is optimal in that it has the least effect on the living body, other materials such as polypropylene, polyethylene, and polycarbonate can also be used with minimal invasiveness. The shape of the housing may be cylindrical, rectangular, or hexagonal, and the tip of the housing may be sharpened into a cone or pyramid shape. If it is sharpened, it may be easier to insert it into the affected area.

[0012] In addition, since the outer diameter of the housing is 2.9 mm or less, preferably 2.8 mm or less, it can be inserted into the treatment tool storage space (inner diameter 2.9 mm) at the tip of a general endoscope, and by operating the endoscope, the bioembedded ultraviolet irradiation device can be pushed out from the treatment tool storage space at the tip and inserted into the affected area with high positional accuracy or removed from the affected area. A dedicated insertion tool or removal tool described later may be used instead of the endoscope.

[0013] Since the housing is made of a flexible material, it may be bent in the middle of the longitudinal direction into a dogleg or arc shape before being inserted into the affected area, or may have a shape memory effect so that it is straight when inserted with an endoscope or a tool, and curved inside the body after being inserted into the affected area. This makes it possible to set the receiving coil in a direction suitable for receiving power. It is also possible to suppress positional deviation from the affected area by curving or bending it. In order to prevent positional deviation from the affected area, a convex or concave portion may be formed on the outer circumferential surface of the housing. The convex or concave portion may be a ring-shaped or helical shape that is coaxial with the central axis of the housing. In the case of a helical shape, the bioimplantable ultraviolet irradiation device may be rotated using an endoscope or a tool and screwed into the affected area.

[0014] The bioimplantable ultraviolet irradiation device of aspect 4 is any one of aspects 1 to 3, and includes a control circuit within the housing that receives AC current from the receiving coil and supplies DC current or DC pulse current to the ultraviolet light-emitting element in a forward voltage range capable of lighting the ultraviolet light-emitting element.

[0015] According to this bioimplantable ultraviolet irradiation device, the control circuit receives an AC current from the receiving coil, rectifies and adjusts the voltage, and supplies a DC current or a DC pulse current within a forward voltage range capable of lighting the ultraviolet light emitting element to the ultraviolet light emitting element, so that the ultraviolet light emitting element can emit light stably continuously or in pulses. In the case of pulse emission, the peak emission intensity can be increased compared to the power generated by the receiving coil of the ultraviolet light emitting element.

[0016] A bioimplantable ultraviolet irradiation system according to a fifth aspect of the present invention includes a bioimplantable ultraviolet irradiation device according to any one of the first to fourth aspects, and a wireless power supply device for wirelessly supplying power from outside the body to the power receiving coil, the wireless power supply device using any one of an electromagnetic induction method, a magnetic field resonance type electromagnetic induction method, and an electromagnetic wave method.

[0017] According to this bioimplantable ultraviolet irradiation system, a bioimplantable ultraviolet irradiation device is implanted in a living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to cancer cells, and the wireless power supply device generates electric power from the receiving coil using any one of the power supply methods of electromagnetic induction, magnetic field resonance type electromagnetic induction, and electromagnetic wave, and the ultraviolet light emitting element generates ultraviolet light using this electric power and irradiates the cancer cells. This allows a cancer treatment to be performed with low invasiveness, few side effects such as inflammation, and little burden on the patient by inducing high apoptosis in the cancer cells and suppressing the induction of necrosis. The wireless power supply device may be a stationary or portable device. In the case of a portable device, it may be equipped with a battery, a control circuit that generates an alternating current using the power of the battery, and a power transmission coil that generates a magnetic force or an electromagnetic wave using the control circuit. Effect of the Invention

[0018] According to this bioimplantable ultraviolet irradiation device, the bioimplantable ultraviolet irradiation device is implanted in a living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to cancer cells, and power is generated in the power receiving coil by a wireless power supply device from outside the body, and ultraviolet light is generated from the ultraviolet light emitting element using this power to irradiate the cancer cells. This highly induces apoptosis in the cancer cells and suppresses the induction of necrosis, thereby enabling cancer treatment to be performed with minimal invasiveness, fewer side effects such as inflammation, and less of a burden on the patient. [Brief description of the drawings]

[0019] [Figure 1] 1 is a side cross-sectional view of a biological implantable ultraviolet irradiating device according to a first embodiment of the present invention. [Diagram 2] FIG. 4 is a side cross-sectional view of a biological implantable ultraviolet irradiating device according to a second embodiment of the present invention. [Diagram 3] FIG. 2 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to an embodiment of the present invention. [Figure 4] FIG. 11 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to another embodiment of the present invention. [Diagram 5]FIG. 2 is a cross-sectional view showing a state in which the biological implantable ultraviolet irradiating device of the first embodiment is used. [Figure 6] FIG. 11 is a side cross-sectional view of a biological implantable ultraviolet irradiating device according to a third embodiment of the present invention. [Figure 7] FIG. 11 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to another embodiment of the present invention. [Figure 8] FIG. 11 is a side cross-sectional view of a biological implantable ultraviolet irradiating device according to a fourth embodiment of the present invention. [Figure 9] FIG. 13 is a side cross-sectional view of a biological implantable ultraviolet irradiating device according to a fifth embodiment of the present invention. [Figure 10] FIG. 11 is a circuit diagram of a biologically implantable ultraviolet irradiation device according to another embodiment of the present invention. [Figure 11] FIG. 11 is a plan view illustrating an example of a power transmission coil according to another embodiment of the present invention. [Figure 12] 1 is a plan view showing a state in which the biological implantable ultraviolet irradiating device is set in an insertion jig for the biological implantable ultraviolet irradiating device. FIG. [Figure 13] 11 is a plan view showing a state in which the biological implantable ultraviolet irradiating device is pushed out from an insertion jig for the biological implantable ultraviolet irradiating device. FIG. [Figure 14] 10 is a cross-sectional view showing a state in which the biologically embedded ultraviolet irradiation device is inserted into cancer cells from the insertion tool. FIG. [Figure 15] 11 is a cross-sectional view showing a state in which the insertion jig is pulled out after the biological implantable ultraviolet irradiating device is inserted. FIG. [Figure 16] FIG. 2 is a plan view of a removal jig for the biological implantable ultraviolet irradiation device. [Figure 17] FIG. 13 is a plan view of the removal jig with the locking claws protruding from the tip. [Figure 18] 11 is a cross-sectional view of a state in which a biologically embedded ultraviolet irradiation device inside a living body is grasped by a removal jig. [Figure 19] 11 is a cross-sectional view of a state in which the bioimplantable ultraviolet irradiation device is being pulled out of a living body by a pulling tool. FIG. [Figure 20]1 is a graph showing an example of the wavelength spectrum of ultraviolet light emitted by an ultraviolet light emitting element used in a biological implantable ultraviolet irradiation device. [Figure 21] FIG. 1 is a perspective view showing a test device for comparing the effects of irradiating cancer cells with ultraviolet light to kill the cancer cells. [Figure 22] 1 is a graph comparing the rates of apoptosis and necrosis induced in cancer cells when the wavelength and total dose of ultraviolet light were changed. [Diagram 23] 1 is a graph comparing the survival rate of cancer cells when the wavelength and total amount of ultraviolet light irradiation are changed. [Figure 24] 1 is a graph comparing the apoptosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. [Diagram 25] 1 is a graph comparing the necrosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. [Figure 26] 1 is a graph comparing the rates of apoptosis and necrosis induced in cancer cells when the wavelength and total dose of ultraviolet light were changed. [Figure 27] 1 is a graph comparing the survival rate of cancer cells when the wavelength and total amount of ultraviolet light irradiation are changed. [Figure 28] 1 is a graph comparing the apoptosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. [Figure 29] 1 is a graph comparing the necrosis rate of cancer cells when the wavelength and total irradiation amount of ultraviolet light are changed. [Diagram 30] 1 is a photograph showing samples of colon cancer cells, gastric cancer cells, and breast cancer cells used in the experiment. [Diagram 31] This is a graph showing the apoptosis rate of colon cancer cell, gastric cancer cell, and breast cancer cell samples used in the experiment when they were not exposed to UV light and when they were exposed to 30 J / cm2 of UV light. [Diagram 32] This is a graph showing the cell survival rate of healthy cells (human skin fibroblasts) when not exposed to UV light and when exposed to 10, 20, and 30 J / cm2. [Diagram 33]This is a graph showing the cell mortality rate of healthy cells (human skin fibroblasts) when they were not exposed to UV light and when they were exposed to 10, 20, and 30 J / cm2. [Diagram 34] These are optical microscope images (100x) of healthy cells (human skin fibroblasts) without UV exposure and after exposure to 10, 20, and 30 J / cm2 of UV light. [Diagram 35] 1 is a photograph of a prototype implantable ultraviolet irradiation device. [Diagram 36] This is a photograph of the prototype bioimplantable ultraviolet irradiation device when illuminated. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Hereinafter, an embodiment of the present invention will be described in detail with reference to the drawings. [First embodiment of the implantable ultraviolet irradiation device] 1 is a side cross-sectional view showing a first embodiment of a bioimplantable ultraviolet irradiating device according to the present invention. This bioimplantable ultraviolet irradiating device 1 has a power receiving coil 2 for receiving wireless power supply, a control circuit 4 for generating a direct current from an alternating current generated by the power receiving coil 2, an ultraviolet emitting element 6 for emitting ultraviolet light by the direct current from the control circuit 4, and a housing 10 for accommodating these.

[0021] The receiving coil 2 is provided with a winding 2B formed by winding a conductive wire of copper, aluminum or the like with an insulated surface many times in a spiral shape around a cylindrical bobbin 2A, and generates an AC current of the same frequency as the transmitting coil 31 by induced electromotive force upon receiving magnetic flux generated by a transmitting coil 31 described later. The receiving coil 2 in this embodiment is disposed coaxially with the housing 10, and the thickness, number of turns, and winding pitch of the conductive wire of the winding 2B are appropriately set corresponding to the frequency and strength of the AC current supplied to the transmitting coil 31. The bobbin 2A may be formed of a material such as a non-magnetic plastic if the frequency of the AC magnetic flux received by the receiving coil 2 is high, and may be formed of a magnetic material such as ferrite if the frequency of the AC magnetic flux received by the receiving coil 2 is low.

[0022] The control circuit 4 converts the AC current generated by the power receiving coil 2 into a DC current or DC pulse current that can cause the ultraviolet light emitting element 6 to emit light, and various types can be adopted as follows. (1) The AC current from the receiving coil 2 is simply half-wave or full-wave rectified by a rectifying element such as a diode, and is supplied as is to the ultraviolet light emitting element 6 as a pulsating DC current. It is preferable to have a current control resistor or an overcurrent protection circuit to protect the ultraviolet light emitting element 6 from an overcurrent. The peak voltage of the pulsating current must exceed the light emission voltage of the ultraviolet light emitting element 6. In this case, the ultraviolet light emitting element 6 emits pulsed light in synchronization with the frequency of the magnetic flux generated by the transmitting coil 31.

[0023] (2) The AC current from the receiving coil 2 is half-wave or full-wave rectified by a rectifying element such as a diode, and is smoothed to some extent by a capacitor to produce a DC current with residual ripples, which is then supplied to the UV light emitting element 6. The peak voltage of the DC current must exceed the light emission voltage of the UV light emitting element 6. In this case, the UV light emitting element 6 emits light continuously.

[0024] (3) The AC current from the receiving coil 2 is half-wave or full-wave rectified by a rectifying element such as a diode, and the voltage is increased by a known boost circuit, and the DC current or DC pulse current is supplied to the ultraviolet light emitting element 6. The peak voltage of the DC current must exceed the light emission voltage of the ultraviolet light emitting element 6. In this case, even if the AC voltage from the receiving coil 2 is low, the voltage can be increased to the light emission voltage required by the ultraviolet light emitting element 6 by the boost circuit. If the AC current from the receiving coil 2 does not provide enough power to cause the ultraviolet light emitting element 6 to emit light continuously, the current may be converted to a DC pulse current, and PWM control may be performed to maintain the output voltage by automatically lowering the duty ratio, which is the pulse width divided by the period. In this case, the ultraviolet light emitting element 6 emits light continuously if the AC power generated by the receiving coil 2 is sufficiently large, and emits light in pulses if the AC power generated by the receiving coil 2 is not sufficient for continuous emission.

[0025] 3 shows an example of a circuit in which the AC current from the power receiving coil 2 is full-wave rectified by a rectifier circuit 12 such as a diode bridge, and the voltage of the DC boosted by a boost circuit 14 is supplied to the ultraviolet light emitting element 6. The voltage of the DC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6. 4 shows an example of a circuit in which the AC current from the power receiving coil 2 is full-wave rectified by a rectifier circuit 12 such as a diode bridge, and the voltage is increased by a pulse control circuit 16 that performs PWM control, resulting in a DC pulse current PC that is supplied to the ultraviolet light emitting element 6. The voltage of the DC pulse current PC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6.

[0026] (4) The control circuit 4 may include a resonant circuit with the AC magnetic flux generated by the power receiving coil 2, and may further include the circuits (1) to (3) described above. As the resonant circuit with the power receiving coil 2, a capacitor of a predetermined capacitance may be connected in parallel with the power receiving coil 2. As this capacitor, a fixed capacitance capacitor may be used, or a variable capacitance capacitor that adjusts the resonant frequency within a certain range in response to fluctuations in the frequency received from the power transmitting coil 31 may be used, or resonance may be achieved using the line capacitance of the winding 2B of the power receiving coil 2.

[0027] The ultraviolet light emitting element 6 has an emission wavelength peak in the ultraviolet wavelength range of 300 nm to 400 nm. Experiments by the present inventor have revealed that by irradiating cancer cells with ultraviolet light in this wavelength range, apoptosis can be highly induced in the cancer cells and the induction of necrosis can be suppressed, thereby enabling cancer treatment that is less invasive, has fewer side effects such as inflammation, and places less of a burden on the patient. The ultraviolet light emitting element 6 may have an emission wavelength peak between 330 nm and 395 nm, and in this case, experiments by the present inventor have confirmed that the ultraviolet light emitting element 6 is highly effective in inducing apoptosis in cancer cells selected from breast cancer, skin cancer, stomach cancer, and leukemia.

[0028] The ultraviolet light emitting element 6 may be one specially designed for the present invention, but it is also possible to use ultraviolet light emitting diodes that are generally available on the market. Generally available ultraviolet light emitting diodes in the UVA1 region include those for 340 nm, 365 nm, 375 nm, 385 nm, 392.5 nm, and 395 nm, and have rated voltages of 340 nm: 4.6 to 4.8 V, 365 nm: 3.80 to 3.85 V, 375 nm: 3.40 V, 385 nm: 3.35 V, and 395 nm: 3.30 V, but are not limited to these.

[0029] The ultraviolet light emitting element 6 is fixed in the housing 10 by a support 8. A lens 10B that is transparent to the ultraviolet light emitted by the ultraviolet light emitting element 6 is provided in the light emission direction of the ultraviolet light emitting element 6 and seals the tip of the housing 10. If the entire housing 10 is formed from a material that is transparent to the ultraviolet light emitted by the ultraviolet light emitting element 6, it is possible to configure the housing 10 without providing the lens 10B. The rear end of the housing 10 is sealed as an end portion 10C, and the inside of the housing 10 is kept airtight.

[0030] Materials for the housing 10 include resins that are less invasive to the living body, and glass and ceramics that are less likely to break. In particular, amorphous fluororesin that is less invasive is optimal in that it has little effect on the living body, but polypropylene, polyethylene, polycarbonate, and the like can also be used. The shape of the housing 10 may be cylindrical, square tubular, or hexagonal tubular, with a cylindrical shape being particularly preferable. The tip of the housing 10 may be hemispherical, or may be sharpened into a cone or pyramid shape. If it is sharp, it may be easier to insert it into the affected area.

[0031] When used together with an endoscope, the outer diameter of the housing 10 is preferably 2.9 mm or less, and more preferably 2.8 mm or less. In this case, it can be inserted into the treatment tool storage space (usually 2.9 mm in inner diameter) at the tip of a general endoscope, and by operating the endoscope, the biomedical implantable ultraviolet irradiation device 1 can be pushed out of the treatment tool storage space at the tip and inserted into the affected area with high positional accuracy. A dedicated insertion tool or removal tool described later may be used instead of the endoscope.

[0032] 5 is a cross-sectional view of a living body showing a living body implantable ultraviolet irradiation system using the living body implantable ultraviolet irradiation device 1 and a method of using the living body implantable ultraviolet irradiation device 1. The living body implantable ultraviolet irradiation device 1 is inserted into normal cells 20 of a living body by an endoscope or an insertion tool, and is held in a state in which the lens 10B is directed toward cancer cells 24 occurring inside tissue consisting of normal cells 20, or in a state in which the lens 10B is inserted into the cancer cells 24. The number of living body implantable ultraviolet irradiation devices 1 inserted into the affected area is not limited to one, and a required number of devices are inserted into the living body at a required position and angle depending on the size of the affected area including the cancer cells 24.

[0033] A compress 30 having a power transmission coil 31 therein is attached and fixed to the surface of the skin 22 corresponding to the affected area by an adhesive or the like. Note that the present invention is not limited to fixing by a compress, and the power transmission coil 31 may be fixed along the skin 22 by any other method. Inside the compress 30, the power transmission coil 31 is arranged in a planar state in an electrically insulated state as shown in FIG. 11, and is connected to a power transmission unit 34 via a cord 32. The power transmission unit 34 has a battery 36, a control circuit 38, and an operation panel 40, and can be carried by the patient on a belt or the like (not shown). The control circuit 38 generates an AC current upon receiving power from the battery 36, and supplies the AC power to the power transmission coil 31 via the cord 32, causing the power transmission coil 31 to generate an AC magnetic flux. Note that the power transmission unit 34 does not necessarily have to be a portable type, and can also be implemented as a stationary type.

[0034] The frequency of the AC magnetic flux generated by the power transmitting coil 31 is not limited in the present invention, but is preferably in the range of 10 kHz to 20 MHz, taking into consideration the power receiving efficiency by the power receiving coil 2.

[0035] After the power receiving coil 2 receives an AC magnetic flux and generates an AC current, the AC current is converted into a DC current or a DC pulse current by the control circuit 4 and supplied to the UV light emitting element 6, which emits UV light L continuously or in a pulsed form. The emitted UV light L is irradiated to the cancer cells 24 through the lens 10B, and by continuing this irradiation for a certain period of time, it is possible to highly induce apoptosis in the cancer cells 24 and kill at least a part of the cancer cells 24, while suppressing the induction of necrosis and reducing side effects such as inflammation. In addition, since the UV light L penetrates the inside of the cancer cells 24 over a certain distance, not only a single layer of the cancer cells 24 but also multiple layers of the cancer cells 24 can be killed. After all or a part of the cancer cells 24 are induced to apoptose, the treatment is completed by removing the bioimplantable UV irradiation device 1 from the normal cells 20 in the living body using an endoscope or a removal tool described later.

[0036] The control circuit 38 estimates the power supplied from the power receiving coil 2 to the ultraviolet light emitting element 6 from the state of the AC current flowing to the power transmitting coil 31, and performs feedback control to increase the power supplied to the power transmitting coil 31 when magnetic coupling is poor due to the distance or orientation between the power transmitting coil 31 and the power receiving coil 2, and to reduce the power supplied to the power transmitting coil 31 when magnetic coupling between the power transmitting coil 31 and the power receiving coil 2 is good, thereby making the intensity of ultraviolet light generated by the ultraviolet light emitting element 6 constant. The operation panel 40 switches the control circuit 38 on and off, and adjusts the intensity and frequency of the AC current supplied to the power transmitting coil 31, so that the ultraviolet light emitting element 6 generates ultraviolet light of the required intensity.

[0037] The power transmitting unit 34 may be provided with a storage device that records the power value transmitted from the power transmitting coil 31 to the power receiving coil 2 over time, and a communication device that transmits the power value by wireless signal to a recording device outside the power transmitting unit 34. In this case, it is possible to quantitatively confirm the therapeutic effect from the information in the recording device.

[0038] [Second embodiment of the bioimplantable ultraviolet irradiation device] Fig. 2 shows a second embodiment of the bioimplantable ultraviolet irradiating device 1. In this second embodiment, the power receiving coil 2 is different from that in the first embodiment, and the power receiving coil 2 is formed by winding a winding 2B around an elliptical or oval bobbin 2A having an axis perpendicular to the longitudinal direction of the housing 10. The other configurations of the second embodiment are similar to those of the bioimplantable ultraviolet irradiating device 1 in Fig. 1, and therefore the description thereof is incorporated herein.

[0039] In this second embodiment, the power receiving coil 2 generates power by the magnetic flux from a direction perpendicular to the longitudinal direction of the housing 10, so that even when the bioimplantable ultraviolet irradiating device 1 is embedded in a state nearly parallel to the skin 22, power can be transmitted from the power transmitting coil 31 of the compress 30 attached to the skin 22. Therefore, depending on the embedding angle of the bioimplantable ultraviolet irradiating device 1 into the living body, it is possible to select and use the bioimplantable ultraviolet irradiating device 1 of Fig. 1 or the bioimplantable ultraviolet irradiating device 1 of Fig. 2.

[0040] [Third embodiment of the implantable ultraviolet irradiation device] FIG. 6 shows a third embodiment of the bioimplantable ultraviolet irradiation device 1. The third embodiment is characterized in that the control circuit 4 is simplified to reduce the overall size. The power receiving coil 2 is coaxially arranged in a housing 10 with a short overall length, and as shown in FIG. 7, the lead wire of the power receiving coil 2 is directly connected to the lead wire of the ultraviolet light emitting element 6. As the control circuit, a diode 42 is connected in parallel with the ultraviolet light emitting element 6 in the opposite direction to the ultraviolet light emitting element 6. The diode 42 serves to prevent the ultraviolet light emitting element 6 from being destroyed by a reverse voltage, and the ultraviolet light emitting element 6 generates pulsed light PL in synchronization with the AC magnetic flux supplied from the power transmitting coil 31. The peak voltage of the DC pulse current PC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6.

[0041] The tip of the ultraviolet light emitting element 6 is sharpened into a quadrangular pyramid shape by scraping off the plastic coating, and is exposed from the tip of the housing 10. The other configurations of the third embodiment are similar to those of the bioimplantable ultraviolet irradiating device 1 in Fig. 1, so the description of the first embodiment will be cited.

[0042] According to the third embodiment, since the overall length of the bioimplantable ultraviolet irradiating device 1 is short, even when the cancer cells 24 are located at a shallow position in the biological tissue, the bioimplantable ultraviolet irradiating device 1 can be easily inserted into the affected area and maintained in a certain position. In addition, since the tip of the ultraviolet emitting element 6 is sharp, it has an advantage that it can be easily inserted into the living body.

[0043] [Fourth embodiment of the bioimplantable ultraviolet irradiation device] FIG. 8 shows a fourth embodiment of the bioimplantable ultraviolet irradiating device 1. In this fourth embodiment, the housing 10 is bendable at the center 10D, and the bioimplantable ultraviolet irradiating device 1 can be bent in a dogleg or curved shape. According to this fourth embodiment, the axial direction of the power receiving coil 2 and the optical axis direction of the ultraviolet ray of the ultraviolet ray light emitting element 6 can be changed, so that even if the optical axis of the ultraviolet ray light emitting element 6 is arranged inclined with respect to the surface of the skin 22 in the living body, the axial direction of the power receiving coil 2 can be arranged at an angle close to perpendicular to the surface of the skin 22. Therefore, it is possible to improve the efficiency of receiving power from the power transmitting coil 31. In addition, according to the fourth embodiment, there is a possibility that the effect that the bioimplantable ultraviolet irradiating device 1 is less likely to come off from the living body can be obtained.

[0044] In order to bend the housing 10 at the bent portion 10D, the housing 10 may be bent before the biological implantable ultraviolet irradiating device 1 is embedded, or the bent portion 10D may be bent during or after the device is embedded in the living body. Also, the housing 10 may be made to memorize a curved or bent shape, and may be curved or bent to return to the memorized shape after being embedded in the living body from the endoscope.

[0045] [Fifth embodiment of the bioimplantable ultraviolet irradiation device] FIG. 9 shows a fifth embodiment of the bioimplantable ultraviolet irradiating device 1. In this fifth embodiment, in order to widen the ultraviolet irradiating area from the tip of the bioimplantable ultraviolet irradiating device 1, a first ultraviolet emitting element 6 with an ultraviolet irradiating direction facing forward in the direction of the housing central axis and a plurality of (for example, two to four) second ultraviolet emitting elements 6 with an ultraviolet irradiating direction inclined at a certain angle (90° in the figure) with respect to the housing central axis are arranged at the tip of the housing 10. The second ultraviolet emitting elements 6 are preferably arranged at equal intervals around the housing central axis. The lens 10B has a cylindrical portion with a long U-shaped cross section and is made of a material that transmits ultraviolet light so that the ultraviolet ray L can be emitted at a wide irradiation angle. The first and second ultraviolet emitting elements 6 are connected in parallel or in series to each other and emit ultraviolet rays of the same wavelength at the same time. Lens 10B may be made of a material that does not scatter ultraviolet light, but inner surface 10E and / or outer surface of lens 10B may be a light scattering surface that scatters ultraviolet light emitted by first and second ultraviolet light emitting elements 6, or lens 10B may be made of a light scattering material that scatters ultraviolet light. When lens 10B has a scattering effect, it is possible to further expand the ultraviolet light irradiation area.

[0046] According to the fifth embodiment, the implantable ultraviolet irradiating device 1 emits ultraviolet rays over a wide angle from its tip, so that it is possible to increase the area over which ultraviolet rays can be irradiated onto the cancer cells 24, thereby expanding the region in which a therapeutic effect can be obtained.

[0047] [Sixth embodiment of the bioimplantable ultraviolet irradiation device] 10 shows a sixth embodiment of the bioimplantable ultraviolet irradiating device 1. In this sixth embodiment, a first ultraviolet irradiating element 6B, a second ultraviolet irradiating element 6C, and a third ultraviolet irradiating element 6D, each of which generates ultraviolet light with a different emission wavelength, are arranged inside the tip of the housing 10, and whichever element emits the ultraviolet light is irradiated to the front of the housing 10 through the lens 10B.

[0048] Within the housing 10 are provided a rectifier circuit 12 such as a diode bridge that rectifies the AC current from the receiving coil 2, a boost circuit 14 that generates a direct current DC by increasing the voltage from the rectified DC, and a switching circuit 43 that switches the boosted direct current or DC pulse current to only one of the first ultraviolet light-emitting element 6B, the second ultraviolet light-emitting element 6C, and the third ultraviolet light-emitting element 6D.

[0049] The first ultraviolet light-emitting element 6B, the second ultraviolet light-emitting element 6C, and the third ultraviolet light-emitting element 6D all generate ultraviolet light, but the wavelengths are different, for example, the first ultraviolet light-emitting element 6B is 340 nm, the second ultraviolet light-emitting element 6C is 365 nm, and the third ultraviolet light-emitting element 6D is 385 nm. According to the inventor's experiments, the ultraviolet light wavelengths that are likely to induce apoptosis and that are unlikely to induce necrosis may differ depending on the type of cancer cell, so if ultraviolet light of any suitable wavelength can be selected from the outside and emitted, it will be possible to use it to treat multiple types of cancer.

[0050] The switching circuit 43 has a frequency detection circuit that detects the frequency of the AC current from the winding 2B before it is rectified by the rectifier circuit 12, and if this frequency detection circuit determines that the frequency is A, it supplies the output power of the control circuit 14 to the first ultraviolet light-emitting element 6B, if it determines that the frequency is B, it supplies the output power of the control circuit 14 to the second ultraviolet light-emitting element 6C, and if it determines that the frequency is C, it supplies the output power of the control circuit 14 to the third ultraviolet light-emitting element 6D.

[0051] Meanwhile, the control circuit 38 of the power transmission unit 34 can set the frequency of the AC current supplied to the power transmission coil 31 by the operation panel 40 to any one of frequencies A, B, and C. Therefore, according to the bioimplantable ultraviolet irradiation device 1 of the sixth embodiment and the bioimplantable ultraviolet irradiation system using the same, there is an advantage that the ultraviolet wavelength generated by the bioimplantable ultraviolet irradiation device 1 can be selected from a plurality of types by operating the operation panel 40, and the type of cancer cells to be treated can be selected.

[0052] [Insertion tool for implantable ultraviolet irradiation device] The biological implantable ultraviolet irradiating device 1 of the present invention can be inserted into the affected area using an endoscope as described above, but it can also be inserted into the affected area using an insertion tool as shown in FIGS.

[0053] As shown in Figs. 12 and 13, the insertion tool 50 has a cylindrical main body 51, an elongated cylindrical needle 52 extending coaxially from the tip of the main body 51, and a cutting edge 54 formed at the tip of the needle 52, and an opening 56 is formed at the base of the cutting edge 54. The inside of the needle 52 has an inner diameter that allows the bioimplantable ultraviolet irradiation device 1 to pass through, and the bioimplantable ultraviolet irradiation device 1 can be removed to the outside through the opening 56. A shaft 58 is slidably arranged coaxially inside the main body 51 and the needle 52. A slit 59 is formed on the circumferential surface of the main body 51, extending from near the rear end of the main body 51 to near the tip, and a knob 60 is attached to the rear end of the shaft 58 through the slit 59. When the knob 60 is tightened, the shaft 58 is fixed to the main body 51 at any position.

[0054] To insert the bioimplantable ultraviolet irradiating device 1 into a living body using the insertion tool 50, first fix the knob 60 at the rear end of the slit 59, and load the bioimplantable ultraviolet irradiating device 1 into the needle 52 through the opening between the front end of the slit 59 and the shaft 58, as shown in Fig. 12. The ultraviolet emitting element 6 of the bioimplantable ultraviolet irradiating device 1 is oriented toward the blade tip 54.

[0055] Next, as shown in FIG. 14, after the patient is partially anesthetized, surgical X-ray imaging devices 62 are placed above and below the affected area, and while checking the position of the tumor while watching the monitor 64, the needle 52 of the insertion tool 50 is inserted into the living body to the position where the cancer cells 24 are located. In this state, the knob 60 is loosened and the shaft 58 is moved forward along the slit 59, and the bio-implantable ultraviolet irradiation device 1 is pushed out from the opening 56 and inserted into the normal cells 20 at the position where the ultraviolet light from the ultraviolet light emitting element 6 hits the cancer cells 24. After the insertion is completed, the insertion tool 50 is pulled out of the living body as shown in FIG. 15. This insertion operation is repeated to set the required number of bio-implantable ultraviolet irradiation devices 1 at the affected area. Thereafter, the ultraviolet light from the ultraviolet light emitting element 6 is irradiated onto the cancer cells 24 by passing electricity from the power transmission unit 34 to the power transmission coil 31, thereby inducing high apoptosis in the cancer cells 24 and suppressing the induction of necrosis, thereby making it possible to perform cancer treatment that is minimally invasive and has few side effects such as inflammation.

[0056] [Removal tool for implantable ultraviolet irradiation device] The biological implantable ultraviolet irradiating device 1 of the present invention can be extracted from the living body using an endoscope as described above, but it can also be extracted from the living body using an extraction tool 70 as shown in FIGS.

[0057] As shown in Figs. 16 and 17, the extraction jig 70 has a cylindrical main body 71, an elongated cylindrical needle 72 extending coaxially from the tip of the main body 71, and a cutting edge 74 formed at the tip of the needle 72, with an opening 76 formed at the base of the cutting edge 74. The inside of the needle 72 has an inner diameter that allows the bioimplantable ultraviolet irradiation device 1 to pass through, and the bioimplantable ultraviolet irradiation device 1 can be inserted into the inside through the opening 76. A tube 78 is slidably arranged coaxially inside the main body 71 and the needle 72. A slit 77 is formed on the circumferential surface of the main body 71, and a knob 80 is attached to the rear end of the tube 78 through the slit 77. When the knob 80 is tightened, the tube 78 is fixed to the main body 71 at any position. A pair of locking claws 79 are slidably disposed inside the tube 78, and the locking claws 79 open when pulled out from the tip of the tube 78, and close when pulled back into the tube 78, making it possible to grip the bioimplantable ultraviolet irradiation device 1. The tube 78 is provided with a set screw 82 for fixing the position of the locking claws 79.

[0058] In order to retrieve the bioimplantable ultraviolet irradiation device 1 from the living body using the extraction tool 70, the patient is partially anesthetized, and then, as shown in FIG. 18, surgical X-ray imaging devices 62 are placed above and below the affected area, and while checking the location of the tumor by looking at the monitor 64, the needle 72 of the extraction tool 70 is inserted into the living body, and the tip of the needle 72 faces the rear end of the bioimplantable ultraviolet irradiation device 1. In this state, the knob 80 is loosened to move the tube 78 forward, and the locking screw 82 is loosened to push the locking claw 79 out of the tube 78, and the rear end of the bioimplantable ultraviolet irradiation device 1 is clamped by the open locking claw 79. Next, as shown in FIG. 19, the locking claw 79 is pulled into the tube 78, and the locking claw 79 grips the bioimplantable ultraviolet irradiation device 1, and the locking screw 82 is fixed in this state. Furthermore, the knob 80 is slid toward the rear end side to accommodate the bioimplantable ultraviolet irradiation device 1 in the sleeve 72. Then, by pulling out the removal jig 70 from the living body, the living body implantable ultraviolet irradiating device 1 can be removed.

[0059] By using such an insertion tool 50 and extraction tool 70, the bioimplantable ultraviolet irradiation device 1 can be safely and easily inserted into and removed from the body, thereby increasing the convenience of the bioimplantable ultraviolet irradiation device 1 and the system.

[0060] Various embodiments of the present invention have been described above, but the present invention is not limited to these, and within the scope of the claims, the features of each embodiment may be combined with each other, and configurations that are not essential to the present invention may be removed. EXAMPLES

[0061] Next, the results of experiments conducted by the present inventors on UV irradiation of various cancer cells will be explained, and the effects of the present invention will be described in detail.

[0062] Fig. 20 is a graph showing the characteristics of the commercially available ultraviolet light emitting element (ultraviolet light emitting diode) used in this experimental example, with the vertical axis being light intensity (arbitrary units) and the horizontal axis being wavelength (nm). The respective peak wavelengths were 340 nm, 365 nm, and 385 nm as specified. The luminous flux / radiant flux of the 340 nm ultraviolet light emitting element was 70 mW, and the emission voltage was 4.8 V. The luminous flux / radiant flux of the 365 nm ultraviolet light emitting element was 1200 mW, and the emission voltage was 3.80 V. The luminous flux / radiant flux of the 385 nm ultraviolet light emitting element was 550 mW, and the emission voltage was 3.35 V.

[0063] Figure 21 is a perspective view showing the ultraviolet irradiation device, light emission control device, and computer used in this experiment. The ultraviolet light-emitting diode, which was placed facing downwards in the central ultraviolet irradiation device, irradiated ultraviolet light onto cancer cells in a petri dish placed below. The ultraviolet light-emitting diode was constantly cooled using a cooling fan and a heat sink. Pathogenic cells of skin lymphoma (Jurkat T cells) or skin cancer (melanoma cells) were placed in the petri dish to carry out the experiment.

[0064] [Apoptosis / necrosis induction experiment of pathogenic cells (Jurkat T cells) of cutaneous lymphoma] Jurkat T cells were cultured for 48 hours in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and CO2:5%. The grown Jurkat T cells were washed and replaced with PBS medium in 36 petri dishes. Using the device shown in Figure 21, the pathogenic cells in the petri dishes were irradiated with ultraviolet light using the ultraviolet light-emitting diodes of 340 nm, 365 nm, and 385 nm. The irradiation conditions are shown in Table 1.

[0065] [Table 1]

[0066] Since the luminous efficiency of ultraviolet light-emitting diodes differs depending on the ultraviolet wavelength, the irradiation distance to the pathogenic cells was adjusted to keep the irradiation intensity constant. As a result, the irradiation intensity, total irradiation amount, and irradiation time in Table 1 were the same for all three wavelengths.

[0067] After UV irradiation, the pathogenic cells were cultured in cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% CO2 for 24 hours. After culture, the pathogenic cells in each dish were stained with Annexin V and PI, and then analyzed by flow cytometry (FACS) using a flow cytometer. If Jurkat T cells are in a normal state without apoptosis induction, membrane phospholipids (phosphatidylserine PS) are present on the inside of the cell membrane and there is no damage to the cell membrane, so the PI reagent is not taken up into the cell and does not bind to the nuclear DNA. However, if apoptosis induction occurs in the pathogenic cells, apoptotic and necrotic cells are stained with both Annexin V and PI, so quantitative analysis of apoptotic and necrotic cells can be performed by flow cytometry.

[0068] FIG. 22 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2This is a graph showing the results of flow cytometry analysis showing the densities of live cells, apoptosis-induced cells, and necrosis-induced cells of pathogenic cells in each case of irradiation with 1000 u / s. At all wavelengths, the number of apoptosis-induced cells increased as the total irradiation dose increased, but the number of necrosis-induced cells hardly increased. In addition, the shorter the wavelength, the fewer the final live cells. FIG. 23 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2 This is a graph showing the percentage (%) of viable pathogen cells in each case of irradiation with light of 1000 nm (Tukey-Kramer test, p<0.05, n=3). The higher the total irradiation dose and the shorter the wavelength, the fewer the final viable cells. FIG. 24 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2 10 J / cm 2 (Tukey-Kramer test, p<0.05, n=3) 2 60% or more, 20J / cm 2 70% or more, 30J / cm 2 At shorter wavelengths, apoptosis was induced in more than 80% of cells. FIG. 25 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2 The graph shows the ratio (%) of necrosis-induced pathogen cells in each case irradiated with 30 J / cm (Tukey-Kramer test, p<0.05, n=3). 2 The percentage of cells in which necrosis was induced was less than 2% in all cases. There was no particular effect of the total irradiation dose or wavelength on the induction of necrosis.

[0069] As shown in Figures 22 to 25, in the case of leukemia cells (Jurkat T cells), which are suspended cells, the peak wavelength is 340 nm × 30 J / cm 2 The highest apoptosis induction rate (97%) was observed in the case of 340 nm × 30 J / cm. On the other hand, necrosis induction was observed in the case of 340 nm × 30 J / cm. 2 Even in these cases, the incidence was less than 2%.

[0070] [Apoptosis and necrosis induction experiments in skin cancer (melanoma cells)] Melanoma cells were cultured for 48 hours in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% CO2. The grown melanoma cells were washed and replaced with PBS medium in 36 petri dishes. Using the device shown in Figure 21, ultraviolet light-emitting diodes of 340 nm, 365 nm, and 385 nm were used to irradiate ultraviolet light onto the pathogenic cells in the petri dishes. The irradiation conditions were the same as those in Table 1.

[0071] After UV irradiation, the pathogenic cells were cultured in cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% CO2 for 48 hours. After culture, the melanoma cells in each dish were stained with Annexin V and PI, and then analyzed by flow cytometry (FACS) using a flow cytometer.

[0072] FIG. 26 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2This is a graph showing the results of flow cytometry analysis showing the densities of live cells, apoptosis-induced cells, and necrosis-induced cells in melanoma cells irradiated with UV light at each wavelength. At all wavelengths, the number of apoptosis-induced cells increased as the total irradiation dose increased, but the number of necrosis-induced cells hardly increased. In addition, it was confirmed that, among the three wavelengths, 340 nm and 365 nm were more effective at inducing apoptosis, and 365 nm was particularly effective in inducing apoptosis in melanoma cells. In this way, it was confirmed that the absorption rate of UV light at each wavelength differs depending on the type of cancer.

[0073] FIG. 27 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2 The graph shows the percentage of viable melanoma cells irradiated with a total dose of 30 J / cm (Tukey-Kramer test, p<0.05, n=3). 2 At 340 nm and 365 nm, the survival rate was significantly reduced. FIG. 28 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2 The graph shows the percentage (%) of melanoma cells that underwent apoptosis induction in each case of irradiation with a total dose of 30 J / cm2 (Tukey-Kramer test, p<0.05, n=3). 2 At 340 nm and 365 nm, the proportion of cells in which apoptosis was induced reached nearly 100%. FIG. 29 shows the results for the total irradiation dose of 0 (control), 10 J / cm at wavelengths of 340 nm, 365 nm, and 385 nm. 2 , 20J / cm 2 , 30J / cm 2The percentage of melanoma cells in which necrosis was induced was 5-6% in the control group, whereas the percentage was 10-30 J / cm2 in the control group (Tukey-Kramer test, p<0.05, n=3). 2 Under these conditions, the percentage of cells in which necrosis was induced was less than 1%. There was no particular effect of the difference in total irradiation dose and wavelength on necrosis induction.

[0074] As shown in Figures 26 to 29, in the case of malignant melanoma (skin cancer), which is an adherent cell, the radiation dose was 30 J / cm at peak wavelengths of 340 nm and 365 nm. 2 In the case of 365 nm, apoptosis induction was observed in about 95-98% of melanoma cells. In particular, the apoptosis induction effect in melanoma cells was confirmed to be high in the case of 365 nm. On the other hand, necrosis induction in these cases was about 1% or less.

[0075] As shown by the above results, ultraviolet light in a specific wavelength range is highly effective in inducing apoptosis in cancer cells and suppressing the induction of necrosis. It was also found that the effective peak wavelength and total irradiation amount differ depending on the type of cancer cell.

[0076] [UV irradiation experiments on colon cancer, stomach cancer, and breast cancer pathogenic cells] We conducted ultraviolet irradiation experiments using human colon cancer, stomach cancer, and breast cancer pathogenic cells. Tumors (spheroids) were created with each pathogenic cell type, assuming a realistic situation. The details of the pathogenic cells are as follows: Colorectal cancer cells (E-GFP) Gastric cancer cells (Nawa (N+0)) Breast cancer cells (MCF-7)

[0077] Each pathogenic cell was cultured for 96 hours in a cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% CO2 to create a tumor (spheroid). Figures 30(a)-(c) show photos of each cell after culture in a petri dish, and Figures 30(d)-(f) show microscopic photos (40x) of the cells.

[0078] Using the device shown in Figure 21 and a 365 nm ultraviolet light emitting diode, ultraviolet light was irradiated onto colon cancer, stomach cancer, and breast cancer tumors in a petri dish. The irradiation conditions were total irradiation dose of 0 (control) and total irradiation dose of 30 J / cm. 2 It was decided. The irradiated tumor cells were further cultured in cell growth medium (RPMI1640 + 10% FBS) at 37°C and 5% CO2 for 24 hours, then the tumors were removed from the dish and the cells were loosened. The loosened cells were counted using a hemocytometer to count live cells and apoptotic dead cells, and compared with the unirradiated (control) sample.

[0079] Figure 31(a)-(c) are graphs showing the ratio of live cells to dead cells in colon cancer cells (E-GFP), gastric cancer cells (Nawa (N+0)), and breast cancer cells (MCF-7) without irradiation (control), and Figure 31(d)-(f) are graphs showing the ratio of live cells to dead cells in colon cancer cells (E-GFP), gastric cancer cells (Nawa (N+0)), and breast cancer cells (MCF-7) without irradiation (control), respectively, with irradiation of 30 J / cm 2 1 is a graph showing the ratio of live cells to apoptosis-induced dead cells after 100 μg / ml of UV irradiation.

[0080] As shown in Figure 31, the total irradiation dose was 30 J / cm compared to no UV irradiation (control). 2 It was found that apoptosis (cell death) was induced in the cells exposed to the radiation. Total irradiation dose was 30 J / cm 2 When comparing colon cancer cells, gastric cancer cells, and breast cancer cells irradiated with 365 nm, it was found that colon cancer cells were more susceptible to apoptosis induction. On the other hand, this does not mean that 365 nm is ineffective against gastric cancer cells and breast cancer cells, and the total irradiation dose of 30 J / cm, which was the experimental condition in this study, was ineffective. 2 It was estimated that a higher total dose of irradiation would be necessary. These experimental results demonstrated that the implantable UV irradiation device is effective for cancer treatment by obtaining a sufficient total dose of irradiation.

[0081] [Investigation of the effects of ultraviolet light (365 nm) on human skin fibroblasts] The following experiment was carried out to confirm that UV irradiation of non-cancerous human skin fibroblast cells would not cause abnormalities in healthy cells. Human dermal fibroblasts were cultured in cell growth medium (MEMα + 10% FBS) at 37°C in an environment of 5% CO2 for 72 hours. The grown human dermal fibroblasts were washed and replaced with PBS medium in 15 petri dishes. Using the device shown in Figure 21, the cells in the petri dishes were irradiated with ultraviolet light using a 365 nm ultraviolet light-emitting diode. The irradiation conditions are shown in Table 2. Sham irradiation refers to a total irradiation dose of 30 J / cm2 without ultraviolet light irradiation and with PBS medium added. 2 The cells were then left at room temperature for the same period (16.6 min.) as in Example 1. Under these conditions, the effect of PBS medium on the cells was examined.

[0082] [Table 2]

[0083] After UV irradiation, the cells were cultured in cell growth medium (MEMα + 10% FBS) at 37°C and 5% CO2 for 72 hours. After culture, the cells in each dish were stained with the staining reagent Acridine Orange / Propidium Iodide Stain and analyzed using an automatic fluorescent cell counter.

[0084] Figure 32 shows the results of the comparison of the total UV irradiation doses of 0 (control), simulated irradiation, 10, 20, and 30 (J / cm 2 ) The viability of all samples was close to 100%. Figure 33 shows the results of the comparison of the total UV irradiation doses of 0 (control), simulated irradiation, 10, 20, and 30 (J / cm 2 ) The mortality rate was low at about 2-3%. Figure 34 (a) to (e) show the results for the total UV irradiation dose of 0 (control), simulated irradiation, 10, 20, and 30 (J / cm 2 ) and human skin fibroblasts in each sample taken at 100x magnification. No particular differences were observed between the samples.

[0085] As shown in Figures 32 to 34, no significant difference was observed when comparing the control and the mock irradiation. Therefore, it was found that the PBS medium did not have a negative effect on human dermal fibroblasts. In addition, compared to the control, the total irradiation doses of 10, 20, and 30 J / cm 2 It was found that UV irradiation had no adverse effect on human skin fibroblasts. 2 Even in this case, cell death was limited to only about 3%. These results indicate that the ultraviolet light emitted from the implantable ultraviolet irradiation device has almost no adverse effects on healthy cells.

[0086] Figures 35 and 36 are photographs of a biological implantable ultraviolet irradiation device prototyped by the inventors. Despite its small size (diameter 4.8 mm × total length 12 mm), the ultraviolet light-emitting diode (365 nm) was able to emit light when it received an AC magnetic flux (300 kHz) from the power transmission coil. [Industrial Applicability]

[0087] According to the bioimplantable ultraviolet irradiation device of the present invention, the bioimplantable ultraviolet irradiation device is implanted in a living body at a position where the ultraviolet light emitted by the ultraviolet light emitting element can be irradiated to cancer cells, and electric power is generated in the power receiving coil by a wireless power supply device from outside the body, and ultraviolet light is generated from the ultraviolet light emitting element using this electric power and irradiated to the cancer cells. This highly induces apoptosis in the cancer cells and suppresses the induction of necrosis, thereby enabling cancer treatment that is minimally invasive, has few side effects such as inflammation, and places a small burden on the patient. Therefore, the present invention can be used industrially. [Explanation of symbols]

[0088] 1. Implantable UV irradiation device 2 Receiving coil 2A Bobbin 2B winding 4 Control circuit 6. Ultraviolet light emitting element 6A tip 6B First ultraviolet light emitting element 6C Second ultraviolet light emitting element 6D 3rd ultraviolet light emitting element 8 Support 10. Housing 10A housing body 10B Lens 10C end 10D bent part 12 Rectifier circuit 14 Control circuit 16 Pulse control circuit 20 normal cells 22 Skin 24 Cancer cells L UV light 30 Compress 31 Transmission coil 32 Code 34 Power Transmission Unit 36 Batteries 38 Control circuit 40 Control panel 42 Diode 43 Switching Circuits 50 Insertion jig 51 Main unit 52 Needle 54 Cutting Edge 56 Opening 58 Shaft 59 Slit 60 knob 62 Position Measuring Unit 64 monitors 70 Extraction jig 71 Main unit 72 Needle 74 Cutting Edge 76 Opening 78 tube 79 Locking claw 80 knob 82 Setscrew

Claims

1. A bioimplantable ultraviolet irradiation device comprising: a receiving coil for receiving wireless power supply; an ultraviolet light-emitting element that emits ultraviolet light using power generated by the receiving coil; and a housing that holds the receiving coil and the ultraviolet light-emitting element in a state in which the ultraviolet light emitted by the ultraviolet light-emitting element can be released to the outside, wherein the ultraviolet light-emitting element has a peak emission wavelength between 300 nm and 400 nm.

2. 2. The implantable ultraviolet irradiation device according to claim 1, wherein the ultraviolet light emitting element is a light emitting diode having a peak emission wavelength between 330 nm and 395 nm, and is used to induce apoptosis in cancer cells.

3. 3. The biological implantable ultraviolet irradiation device according to claim 1, wherein the housing is made of amorphous fluororesin, has a cylindrical shape with both ends sealed, and has an outer diameter of 2.9 mm or less.

4. The bioimplantable ultraviolet irradiation device according to claim 1 or 2, characterized in that a control circuit is provided within the housing for receiving an alternating current from the receiving coil and supplying a direct current or a direct current pulse current within a forward voltage range capable of lighting the ultraviolet light emitting element to the ultraviolet light emitting element.

5. 3. A bioimplantable ultraviolet irradiation system comprising: the bioimplantable ultraviolet irradiation device according to claim 1 or 2; and a wireless power supply device for wirelessly supplying power from outside the body to the power receiving coil, wherein the wireless power supply device uses any one of an electromagnetic induction method, a magnetic field resonance type electromagnetic induction method, and an electromagnetic wave method.

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