Implantable ultraviolet irradiation device and implantable ultraviolet irradiation system

The implantable ultraviolet irradiation device addresses the invasive and side-effect-ridden nature of current cancer treatments by using wireless power to generate UV light that selectively induces apoptosis in cancer cells, achieving effective and minimally invasive cancer treatment.

JP7690216B2Active Publication Date: 2025-06-10稲田 シュンコ アルバーノ
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Patent Information

Application Number
JP2023092686
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Filing Date
2023-06-05
Publication Date
2025-06-10
Estimated Expiration
2043-06-05

AI Technical Summary

Technical Problem

Current cancer treatment methods are invasive and come with significant side effects, such as inflammation, and impose a heavy physical burden on patients.

Method used

An implantable ultraviolet irradiation device that uses a power receiving coil for wireless power supply to generate ultraviolet light in the 300-400 nm range, which is selectively absorbed by cancer cells to induce apoptosis while minimizing necrosis.

Benefits of technology

The device enables minimally invasive cancer treatment with reduced side effects and lower patient burden by selectively targeting and eliminating cancer cells through apoptosis induction.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

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
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Description

Technical Field

[0001] The present invention relates to an implantable ultraviolet irradiation device that can be used for cancer treatment and an implantable ultraviolet irradiation system using the same.

Background Art

[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, colorectal cancer, gastric cancer, leukemia, etc., and further development of medical technology is required. Cancer treatment methods are mainly classified into chemotherapy using anticancer drugs, radiation therapy using electromagnetic waves or particle beams, surgical operations such as laparotomy, endoscopic surgery, and laparoscopic surgery, and transplantation operations such as hematopoietic stem cell transplantation and bone marrow transplantation. However, all of them have large invasiveness and side effects and impose a heavy physical burden.

[0003] The inventor has focused on light energy as a treatment method with low invasiveness, few side effects, low physical burden, and low cost, and has explored a technology that can highly induce apoptosis (cell death) of cancer cells by light energy while suppressing the induction of necrosis (necrosis) at a low level. If apoptosis (cell death) can be more generated while suppressing the occurrence of necrosis (necrosis), cancer cells can be effectively reduced while avoiding the occurrence of inflammation caused by cancer treatment. As a result of the inventor's research, it has been found that by irradiating cancer cells with light in a specific ultraviolet region at an appropriate intensity, apoptosis can be highly induced in cancer cells and the induction of necrosis can be suppressed.

[0004] Although implantable light irradiation devices have been partially proposed as in Patent Document 1, no proposal has been made that is effective against cancer cells.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] The problem to be solved by the present invention is to provide an implantable ultraviolet irradiation device that can perform cancer treatment with less invasion, fewer side effects such as inflammation, and less burden on patients.

Means for Solving the Problems

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

[0008] According to this implantable ultraviolet irradiation device, the implantable ultraviolet irradiation device is implanted into the living body at a position where the cancer cells can be irradiated with the ultraviolet light emitted by the ultraviolet light emitting element, and power is generated in the power receiving coil by a wireless power supply device from outside the body. Ultraviolet light is generated from the ultraviolet light emitting element by this power and irradiated onto cancer cells. Thereby, apoptosis can be highly induced in cancer cells, and by suppressing the induction of necrosis, cancer treatment with less invasion, fewer side effects such as inflammation, and less burden on patients can be performed.

[0009] The implantable ultraviolet irradiation device according to Aspect 2 is a light emitting diode in which the ultraviolet light emitting element has a peak in the emission wavelength between 330 nm and 395 nm in Aspect 1. Therefore, it is possible to effectively induce apoptosis in various cancer cells and suppress the induction of necrosis. Therefore, cancer treatment with less invasion, fewer side effects such as inflammation, and less burden on patients can be performed. In addition, in the experimental results described later, effects were confirmed for breast cancer, skin cancer, gastric cancer, and leukemia. However, since it was confirmed by the experiments of the present inventors that cancer cells generally absorb ultraviolet rays of a specific wavelength, it can be inferred that the present invention has the same effect on any other cancer cells (for example, colorectal cancer, esophageal cancer, liver cancer, prostate cancer, uterine cancer, etc.).

[0010] In the case of the body-implantable ultraviolet irradiation device according to Aspect 3, in Aspect 1 or 2, the housing is formed of an amorphous fluororesin and has a cylindrical shape with both ends sealed. Further, the outer diameter of the housing is 2.9 mm or less.

[0011] Since the housing is formed of an amorphous fluororesin and has a cylindrical shape with both ends sealed, it is easy to insert the housing along the longitudinal direction into the living body, and since the waterproof property of the housing is also high, the internal structure of the device can be protected over a long period. Although amorphous fluororesin is optimal in that it has the least influence on the living body, polypropylene, polyethylene, polycarbonate, etc. can also be used with low invasiveness. Further, the shape of the housing may be cylindrical, square columnar, or hexagonal columnar, and the tip of the housing may be tapered into a conical shape or a pyramidal shape. When it is tapered, it may be possible to easily insert it into the affected part.

[0012] Further, 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 accommodation space (inner diameter 2.9 mm) at the tip of a general endoscope, and by operating the endoscope, the body-implantable ultraviolet irradiation device can be pushed out from the treatment tool accommodation space at the tip and inserted into the affected part with high positional accuracy, or removed from the affected part. Instead of the endoscope, a dedicated insertion jig or removal jig described later may be used.

[0013] Since the housing is made of a flexible material, it may be bent at a midpoint in the longitudinal direction to form a "U" shape or an arc shape and inserted into the affected area. Alternatively, it may be given a shape memory effect so that it is straight when inserted with an endoscope or a jig, and curves inside the living body after being inserted into the affected area. This makes it possible to set the power receiving coil in a direction suitable for power reception. Also, it is possible to suppress displacement from the affected area by bending or curving. To prevent displacement from the affected area, convex or concave portions may be formed on the outer peripheral surface of the housing. The convex or concave portions may be ring-shaped or spiral-shaped and coaxial with the central axis of the housing. In the case of a spiral shape, the implantable ultraviolet irradiation device may be rotated using an endoscope or a jig and screwed into the affected area.

[0014] In the implantable ultraviolet irradiation device according to Aspect 4, in any of Aspects 1 to 3, a control circuit is provided in the housing to receive an alternating current from the power receiving coil and supply 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.

[0015] According to this implantable ultraviolet irradiation device, since the control circuit receives an alternating current from the power receiving coil, rectifies and adjusts the voltage, and supplies 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, the ultraviolet light emitting element can stably emit continuous light or pulsed light. When emitting pulsed light, the peak emission intensity can be increased compared to the power generated by the power receiving coil of the ultraviolet light emitting element.

[0016] The implantable ultraviolet irradiation system according to Aspect 5 of the present invention includes an implantable ultraviolet irradiation device according to any of Aspects 1 to 4 and a wireless power supply device for wirelessly supplying power to the power receiving coil from outside the body. The wireless power supply device is any one of a power supply method of an electromagnetic induction method, a magnetic field resonance type electromagnetic induction method, and an electromagnetic wave method.

[0017] According to this implantable ultraviolet irradiation system, an implantable ultraviolet irradiation device is implanted into the living body at a position where cancer cells can be irradiated with the ultraviolet rays emitted by the ultraviolet light-emitting element. Power is generated in the power receiving coil by any one of the power feeding methods of the electromagnetic induction method, the magnetic field resonance type electromagnetic induction method, and the electromagnetic wave method from outside the body by the wireless power feeding device, and ultraviolet rays are generated from the ultraviolet light-emitting element by this power to irradiate cancer cells. As a result, apoptosis can be highly induced in cancer cells, and by suppressing the induction of necrosis, minimally invasive cancer treatment with few side effects such as inflammation can be performed with less burden on the patient. The wireless power feeding device may be a stationary type or a portable device. In the case of a portable device, it may include a battery, a control circuit that generates an alternating current by the power of the battery, and a power transmission coil that generates a magnetic force or an electromagnetic wave by the control circuit.

Advantages of the Invention

[0018] According to this implantable ultraviolet irradiation device, an implantable ultraviolet irradiation device is implanted into the living body at a position where cancer cells can be irradiated with the ultraviolet rays emitted by the ultraviolet light-emitting element. Power is generated in the power receiving coil from outside the body by a wireless power feeding device, and ultraviolet rays are generated from the ultraviolet light-emitting element by this power to irradiate cancer cells. As a result, apoptosis can be highly induced in cancer cells, and by suppressing the induction of necrosis, minimally invasive cancer treatment with few side effects such as inflammation can be performed with less burden on the patient.

Brief Description of the Drawings

[0019]

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Mode for Carrying Out the Invention

[0020] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. [Implantable Ultraviolet Irradiation Device of the First Embodiment] FIG. 1 is a side sectional view showing a first embodiment of an implantable ultraviolet irradiation device according to the present invention. This implantable ultraviolet irradiation device 1 has a power receiving coil 2 for receiving wireless power supply, a control circuit 4 for generating a direct current from the alternating current generated by the power receiving coil 2, an ultraviolet light emitting element 6 that emits ultraviolet light by the direct current from the control circuit 4, and a housing 10 that houses these components.

[0021] The power receiving coil 2 is formed by winding a large number of conductive wires such as copper or aluminum with insulated surfaces in a spiral shape around a cylindrical bobbin 2A to provide a winding 2B. It receives the magnetic flux generated by a power transmission coil 31 described later and generates an alternating current having the same frequency as the power transmission coil 31 by electromagnetic induction. The power receiving coil 2 of this embodiment is arranged 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 intensity of the alternating current supplied to the power transmission coil 31. The bobbin 2A may be formed of a material such as plastic that has no magnetism when the frequency of the alternating magnetic flux received by the power receiving coil 2 is high, or may be formed of a magnetic material such as ferrite when the frequency of the alternating magnetic flux received by the power receiving coil 2 is low.

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

[0023] (2) The alternating current from the power receiving coil 2 is half-wave rectified or full-wave rectified by a rectifying element such as a diode, smoothed to some extent by a capacitor or a condenser, and supplied to the ultraviolet light emitting element 6 as a direct current with ripple remaining. The peak voltage of the direct current needs to exceed the light emitting voltage of the ultraviolet light emitting element 6. In this case, the ultraviolet light emitting element 6 emits light continuously.

[0024] (3) The alternating current from the power receiving coil 2 is half-wave rectified or full-wave rectified by a rectifying element such as a diode, and is supplied to the ultraviolet light emitting element 6 as a direct current or a direct current pulse current with the voltage increased by a known boosting circuit. The peak voltage of the direct current needs to exceed the light emitting voltage of the ultraviolet light emitting element 6. In this case, even when the alternating voltage from the power receiving coil 2 is low, the boosting circuit can increase the voltage to the light emitting voltage required by the ultraviolet light emitting element 6. When the power sufficient to cause the ultraviolet light emitting element 6 to emit light continuously cannot be obtained from the alternating current of the power receiving coil 2, it may be converted into a direct current pulse current, and PWM control may be performed to automatically reduce the duty ratio obtained by dividing the pulse width by the period to maintain the output voltage. In this case, the ultraviolet light emitting element 6 emits light continuously if the alternating power generated by the power receiving coil 2 is sufficiently large, and emits light in pulses if the alternating power generated by the power receiving coil 2 is insufficient for continuous light emission.

[0025] FIG. 3 shows an example of a circuit that full-wave rectifies the alternating current from the power receiving coil 2 by a rectifier circuit 12 such as a diode bridge and supplies a direct current DC with an increased voltage by a booster circuit 14 to the ultraviolet light emitting element 6. The voltage of the direct current DC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6. FIG. 4 shows an example of a circuit that full-wave rectifies the alternating current from the power receiving coil 2 by a rectifier circuit 12 such as a diode bridge and supplies it to the ultraviolet light emitting element 6 as a direct current pulse PC with an increased voltage by a pulse control circuit 16 that performs PWM control. The voltage of the direct current pulse PC is higher than the light emitting voltage VL of the ultraviolet light emitting element 6.

[0026] (4) The control circuit 4 includes a resonance circuit with the alternating magnetic flux generated by the power receiving coil 2, and may further include the circuits of (1) to (3) above. As the resonance circuit with the power receiving coil 2, it is possible to connect a capacitor with a predetermined capacitance in parallel with the power receiving coil 2. As this capacitor, a fixed capacitance capacitor may be used, a variable capacitance capacitor that adjusts the resonance frequency within a certain range according to the fluctuation of the frequency received from the power transmission coil 31 may be used, or the resonance may be achieved by using the inter-turn capacitance of the winding 2B of the power receiving coil 2.

[0027] The ultraviolet light emitting element 6 has a peak of the emission wavelength in the ultraviolet wavelength range of 300 nm to 400 nm. According to the experiments of the present inventor, by irradiating cancer cells with ultraviolet light in this wavelength range, apoptosis can be highly induced in cancer cells, and by suppressing the induction of necrosis, a cancer treatment with low invasiveness, few side effects such as inflammation, and little burden on patients can be performed. The ultraviolet light emitting element 6 may have a peak of the emission wavelength between 330 nm and 395 nm. In this case, it has been confirmed by the experiments of the present inventor that the effect of causing apoptosis in cancer cells particularly selected from breast cancer, skin cancer, gastric cancer, and leukemia is high.

[0028] The ultraviolet light emitting element 6 may be specially designed for the present invention, but it is also possible to use a commercially available ultraviolet light emitting diode. Commercially available ultraviolet light emitting diodes in the UVA1 region generally include those for 340 nm, 365 nm, 375 nm, 385 nm, 392.5 nm, 395 nm, etc. The rated voltages are 340 nm: 4.6 - 4.8 V, 365 nm: 3.80 - 3.85 V, 375 nm: 3.40 V, 385 nm: 3.35 V, 395 nm: 3.30 V, etc., but are not limited thereto.

[0029] The ultraviolet light emitting element 6 is fixed in the housing 10 by the support 8. In the light generation direction of the ultraviolet light emitting element 6, a lens 10B that is transparent to the ultraviolet light generated by the ultraviolet light emitting element 6 is provided to seal the tip of the housing 10. When the entire housing 10 is formed of a material that is transparent to the ultraviolet light generated by the ultraviolet light emitting element 6, a configuration without particularly providing the lens 10B is also possible. 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] Examples of the material of the housing 10 include resins with low invasiveness to the living body, glass and ceramics that are not easily damaged. In particular, amorphous fluororesin with low invasiveness is optimal in that it has little influence on the living body, but polypropylene, polyethylene, polycarbonate, etc. can also be used. The shape of the housing 10 may be cylindrical, square cylindrical, or hexagonal cylindrical, but is particularly preferably cylindrical. The tip of the housing 10 may be hemispherical, or may be pointed in a conical or pyramidal shape. When it is pointed, it may be easier to insert into the affected area.

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

[0032] FIG. 5 is a cross-sectional view of a living body showing an in-vivo implantable ultraviolet irradiation system using the in-vivo implantable ultraviolet irradiation device 1 and a method of using the in-vivo implantable ultraviolet irradiation device 1. This in-vivo implantable ultraviolet irradiation device 1 is inserted into normal cells 20 of a living body by an endoscope or an insertion jig, and is held in a state where the lens 10B is directed at cancer cells 24 generated inside the tissue composed of normal cells 20, or in a state where the lens 10B is inserted into the cancer cells 24. The number of in-vivo implantable ultraviolet irradiation devices 1 inserted into the affected area is not limited to one, and is inserted into the living body at the required positions and angles in the required number according to the size of the affected area including the cancer cells 24.

[0033] On the surface of the skin 22 corresponding to the affected area, a wet compress body 30 having a power transmission coil 31 inside is attached and fixed by an adhesive or the like. In the present invention, it is not limited to fixation by a wet compress, and the power transmission coil 31 may be fixed along the skin 22 by any other method. Inside the wet compress body 30, a power transmission coil 31 as illustrated in FIG. 11 is arranged in a planar shape in an electrically insulated state 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 a patient using a belt or the like (not shown). The control circuit 38 generates an alternating current receiving power from the battery 36, supplies the alternating current power to the power transmission coil 31 through the cord 32, and generates an alternating magnetic flux from the power transmission coil 31. Note that the power transmission unit 34 does not necessarily have to be portable, and can also be implemented as a stationary type.

[0034] The frequency of the alternating magnetic flux generated by the power transmission coil 31 is not limited in the present invention, but considering the power reception efficiency by the power reception coil 2, it is preferably in the range of 10 kHz to 20 MHz.

[0035] After the power reception coil 2 receives the alternating magnetic flux and generates an alternating current, it is converted into a direct current or a direct current pulse current by the control circuit 4 and supplied to the ultraviolet light emitting element 6, and the ultraviolet light emitting element 6 emits ultraviolet light L continuously or in pulses. The emitted ultraviolet light L is irradiated onto the cancer cells 24 through the lens 10B. By continuing this irradiation for a certain period of time, apoptosis can be highly induced in the cancer cells 24 to kill at least a part of the cancer cells 24, and the induction of necrosis can be suppressed, so that side effects such as inflammation generation can be reduced. Since the ultraviolet light L penetrates a certain distance inside the cancer cells 24, not only the cancer cells 24 in a single layer can be killed, but also the cancer cells 24 in multiple layers can be killed. After all or part of the cancer cells 24 are induced to apoptosis, the treatment is completed by removing the in-vivo implanted ultraviolet irradiation device 1 from the normal cells 20 in the living body using an endoscope or a removal jig described later.

[0036] The control circuit 38 estimates the power supplied from the power reception coil 2 to the ultraviolet light emitting element 6 from the state of the alternating current flowing through the power transmission coil 31, and increases the power supplied to the power transmission coil 31 when the magnetic coupling is poor due to the distance or orientation between the power transmission coil 31 and the power reception coil 2, and decreases the power supplied to the power transmission coil 31 when the magnetic coupling between the power transmission coil 31 and the power reception coil 2 is good. Feedback control may be performed to make the ultraviolet intensity 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 alternating current supplied to the power transmission coil 31 so that ultraviolet light of the required intensity is generated from the ultraviolet light emitting element 6.

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

[0038] [Biologically implantable ultraviolet irradiation device of the second embodiment] FIG. 2 shows a second embodiment of the biologically implantable ultraviolet irradiation device 1. In this second embodiment, unlike the first embodiment, the power reception coil 2 uses an elliptical or oval bobbin 2A having an axis in a direction perpendicular to the longitudinal direction of the housing 10, and the winding 2B is wound to form the power reception coil 2. Since the other configurations of the second embodiment are the same as those of the biologically implantable ultraviolet irradiation device 1 in FIG. 1, the description thereof is incorporated herein by reference.

[0039] In this second embodiment, since the power reception coil 2 generates electricity by the magnetic flux from a direction perpendicular to the longitudinal direction of the housing 10, even when the biologically implantable ultraviolet irradiation device 1 is embedded in a state close to being parallel to the skin 22, power can be transmitted from the power transmission coil 31 of the wet compress body 30 attached to the skin 22. Therefore, depending on the embedding angle of the biologically implantable ultraviolet irradiation device 1 into the living body, it is possible to select and use the biologically implantable ultraviolet irradiation device 1 in FIG. 1 and the biologically implantable ultraviolet irradiation device 1 in FIG. 2.

[0040] [Biologically implantable ultraviolet irradiation device of the third embodiment] FIG. 6 shows a third embodiment of the implantable ultraviolet irradiation device 1. This third embodiment is characterized by simplifying the control circuit 4 to reduce the overall size. The power receiving coil 2 is coaxially arranged within a short housing 10 of the entire length. 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, the diode 42 is connected in parallel with the ultraviolet light emitting element 6 in the reverse direction. The diode 42 functions to prevent the ultraviolet light emitting element 6 from being destroyed by reverse voltage, and the ultraviolet light emitting element 6 generates pulsed light PL in synchronization with the alternating magnetic flux supplied from the power transmission coil 31. The peak voltage of the DC pulsed current PC is higher than the light emission voltage VL of the ultraviolet light emitting element 6.

[0041] The tip of the ultraviolet light emitting element 6 has its plastic coating scraped off and is sharpened into a quadrangular pyramid shape, and is exposed from the tip of the housing 10. Since the other configurations of the third embodiment are the same as those of the implantable ultraviolet irradiation device 1 in FIG. 1, the description of the first embodiment is incorporated herein by reference.

[0042] According to this third embodiment, since the overall length of the implantable ultraviolet irradiation device 1 is short, even when the cancer cells 24 are located at a shallow position in the living tissue, it is easy to insert the implantable ultraviolet irradiation device 1 into the affected area and maintain the posture. Further, since the tip of the ultraviolet light emitting element 6 is sharp, it has the advantage of being easily inserted into the living body.

[0043] [Implantable Ultraviolet Irradiation Device of the Fourth Embodiment] FIG. 8 shows a fourth embodiment of the implantable ultraviolet irradiation device 1. In this fourth embodiment, the housing 10 is refractable at the central portion 10D, and the implantable ultraviolet irradiation device 1 can be curved in a U-shape or a curved shape. According to this fourth embodiment, since the axial direction of the power receiving coil 2 and the optical axis direction of the ultraviolet light of the ultraviolet light emitting element 6 can be changed, even when the optical axis of the ultraviolet light emitting element 6 is disposed at an angle 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 disposed at an angle close to perpendicular to the surface of the skin 22. Therefore, it is possible to improve the power reception efficiency from the power transmission coil 31. Further, according to the fourth embodiment, there is also a possibility that an effect that the implantable ultraviolet irradiation device 1 is difficult to come off from the living body can be obtained.

[0044] Note that in order to bend the housing 10 at the bent portion 10D, it may be bent before the implantable ultraviolet irradiation device 1 is implanted, or the bent portion 10D may be refracted during or after being implanted in the living body. Further, a curved shape or a bent shape may be stored in the housing 10, and after being implanted in the living body from the endoscope, it may be curved or bent to return to the stored shape.

[0045] [Implantable Ultraviolet Irradiation Device of Fifth Embodiment] FIG. 9 shows a fifth embodiment of the implantable ultraviolet irradiation device 1. In this fifth embodiment, in order to widen the ultraviolet irradiation area from the tip of the implantable ultraviolet irradiation device 1, a first ultraviolet light emitting element 6 with an ultraviolet irradiation direction facing forward in the housing central axis direction and a plurality (for example, 2 to 4) of second ultraviolet light emitting elements 6 having an ultraviolet irradiation 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 light emitting elements 6 are preferably arranged at equal intervals around the housing central axis. The lens 10B has a U-shaped cross section with a long cylindrical portion and is made of a material that transmits ultraviolet light so that ultraviolet light L can be emitted at a wide irradiation angle. The first and second ultraviolet light emitting elements 6 are connected in parallel or in series with each other and are adapted to emit ultraviolet light of the same wavelength simultaneously. The lens 10B may be made of a material that does not scatter ultraviolet light, but the inner surface 10E and / or the outer surface of the lens 10B may be a light scattering surface that scatters the ultraviolet light emitted by the first and second ultraviolet light emitting elements 6, or the lens 10B may be made of a light scattering material that scatters ultraviolet light. When the lens 10B has a scattering effect, it is possible to further widen the ultraviolet irradiation area.

[0046] According to the fifth embodiment, since the implantable ultraviolet irradiation device 1 emits ultraviolet light over a wide angle from its tip, it is possible to increase the area irradiated with ultraviolet light on the cancer cells 24 and widen the area where a therapeutic effect can be obtained.

[0047] [Implantable Ultraviolet Irradiation Device of the Sixth Embodiment] FIG. 10 shows a sixth embodiment of the implantable ultraviolet irradiation device 1. In this sixth embodiment, a first ultraviolet light emitting element 6B, a second ultraviolet light emitting element 6C, and a third ultraviolet light emitting element 6D that generate ultraviolet light with different emission wavelengths are arranged inside the tip of the housing 10, and ultraviolet light is irradiated forward of the housing 10 through the lens 10B regardless of which one emits light.

[0048] Inside the housing 10, there is provided a rectifying circuit 12 such as a diode bridge that rectifies the alternating current from the power receiving coil 2, a boosting circuit 14 that generates a direct current DC with an increased voltage from the rectified direct current, and a switching circuit 43 that switches and conducts the boosted direct current or direct current 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 for example, the wavelength of the first ultraviolet light emitting element 6B is 340 nm, the wavelength of the second ultraviolet light emitting element 6C is 365 nm, and the wavelength of the third ultraviolet light emitting element 6D is 385 nm, so they have different wavelengths. According to the experiments of the present inventors, since the ultraviolet light wavelengths that are likely to induce apoptosis and less likely to induce necrosis may vary depending on the type of cancer cells, if it is possible to select and emit ultraviolet light of an appropriate wavelength from the outside, it will be possible to use it for the treatment of multiple types of cancer.

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

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

[0052] [Insertion jig for the implantable ultraviolet irradiation device] As described above, the implantable ultraviolet irradiation device 1 of the present invention can be inserted into the affected area using an endoscope, but it can also be inserted into the affected area using an insertion jig as shown in FIGS. 12 to 15.

[0053] As shown in FIGS. 12 and 13, this insertion jig 50 has a cylindrical main body 51, an elongated cylindrical needle 52 extending coaxially from the tip of the main body 51, and a blade tip 54 formed at the tip of the needle 52. An opening 56 is formed at the base of the blade tip 54. The inside of the needle 52 has an inner diameter through which the implantable ultraviolet irradiation device 1 can pass, and the implantable ultraviolet irradiation device 1 can escape to the outside from the opening 56. A shaft 58 is coaxially arranged inside the main body 51 and the needle 52 in a slidable manner. A slit 59 reaching from the vicinity of the rear end to the vicinity of the front end of the main body 51 is formed on the circumferential surface of the main body 51, 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 at an arbitrary position in the main body 51.

[0054] To insert the implantable ultraviolet irradiation device 1 into the living body using the insertion jig 50, as shown in FIG. 12, first fix the knob 60 at the rear end of the slit 59, and load the implantable ultraviolet irradiation device 1 into the needle 52 from the opening formed between the front end of the slit 59 and the shaft 58. The ultraviolet light emitting element 6 of the implantable ultraviolet irradiation device 1 is directed toward the blade tip 54 side.

[0055] Next, as shown in FIG. 14, after the patient is under local anesthesia, surgical X-ray imaging devices 62 are arranged above and below the affected part respectively. While checking the position of the tumor while looking at the monitor 64, the needle 52 of the insertion jig 50 is inserted into the living body to the position where the cancer cells 24 are located. In this state, loosen the knob 60 and move the shaft 58 forward along the slit 59, push out the in-vivo implantable ultraviolet irradiation device 1 from the opening 56, and insert it into the normal cell 20 at the position where the ultraviolet rays from the ultraviolet light emitting element 6 hit the cancer cells 24. When the insertion is completed, as shown in FIG. 15, pull out the insertion jig 50 from the living body. Repeat this insertion operation to set the required number of in-vivo implantable ultraviolet irradiation devices 1 at the affected part. Then, by energizing from the power transmission unit 34 to the power transmission coil 31, irradiate the cancer cells 24 with the ultraviolet rays from the ultraviolet light emitting element 6, highly induce apoptosis in the cancer cells 24, and suppress the induction of necrosis, so that it is possible to perform cancer treatment with less invasion and fewer side effects such as inflammation.

[0056] [Withdrawal jig for in-vivo implantable ultraviolet irradiation device] The in-vivo implantable ultraviolet irradiation device 1 of the present invention can be withdrawn from the living body using an endoscope as described above, but can also be withdrawn from the living body using a withdrawal jig 70 as shown in FIGS. 16 to 19.

[0057] As shown in FIGS. 16 and 17, this extraction jig 70 has a cylindrical main body 71, an elongated cylindrical needle 72 coaxially extending from the tip of the main body 71, and a cutting edge 74 formed at the tip of the needle 72. An opening 76 is formed at the base of the cutting edge 74. The inside of the needle 72 has an inner diameter through which the implantable ultraviolet irradiation device 1 can pass, and the implantable ultraviolet irradiation device 1 can be inserted into the inside from the opening 76. Inside the main body 71 and the needle 72, a tube 78 is coaxially arranged slidably. 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 at an arbitrary position on the main body 71. Inside the tube 78, a pair of locking claws 79 are arranged slidably. When the locking claws 79 are pushed out from the tip of the tube 78, the locking claws 79 open, and when the locking claws 79 are pulled into the inside of the tube 78, the locking claws 79 close, enabling the implantable ultraviolet irradiation device 1 to be grasped. The tube 78 is provided with a set screw 82 for fixing the position of the locking claws 79.

[0058] To recover the implantable ultraviolet irradiation device 1 from the living body using the extraction jig 70, after the patient is partially anesthetized, as shown in FIG. 18, surgical X-ray imaging devices 62 are arranged above and below the affected part, and while checking the monitor 64 to confirm the position where the tumor was located, the needle 72 of the extraction jig 70 is inserted into the living body, and the tip is opposed to the rear end of the implantable ultraviolet irradiation device 1. In this state, the knob 80 is loosened to move the tube 78 forward, the set screw 82 is loosened to push out the locking claws 79 from the tube 78, and the rear end of the implantable ultraviolet irradiation device 1 is clamped by the opened locking claws 79. Next, as shown in FIG. 19, the locking claws 79 are pulled into the tube 78, the implantable ultraviolet irradiation device 1 is grasped by the locking claws 79, and the set screw 82 is fixed in this state. Further, the knob 80 is slid to the rear end side to accommodate the implantable ultraviolet irradiation device 1 in the sleeve 72. Then, by pulling out the extraction jig 70 from the living body, it is possible to remove the implantable ultraviolet irradiation device 1.

[0059] By using such an insertion jig 50 and a withdrawal jig 70, the implantable ultraviolet irradiation device 1 can be safely and easily inserted into and withdrawn from a living body, and the convenience of the implantable ultraviolet irradiation device 1 and the system can be enhanced.

[0060] As described above, various embodiments of the present invention have been described. However, the present invention is not limited to these, and within the scope described in the claims, the features of each embodiment may be combined with each other, or a configuration that is not essential to the present invention may be removed.

Example

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

[0062] FIG. 20 is a graph showing the characteristics of a commercially available ultraviolet light-emitting element (ultraviolet light-emitting diode) used in this experimental example. The vertical axis represents the light intensity (arbitrary unit), and the horizontal axis represents the wavelength (nm). Each peak wavelength was 340 nm, 365 nm, and 385 nm as per the standard. 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] FIG. 21 is a perspective view showing the ultraviolet irradiation device, the light emission control device, and the computer used in this experiment. Ultraviolet rays were irradiated from an ultraviolet light-emitting diode disposed downward in the central ultraviolet irradiation device onto cancer cells in a petri dish disposed below. The ultraviolet light-emitting diode was constantly cooled using a cooling fan and a heat sink. In the petri dish, pathogenic cells (Jurkat T cells) of cutaneous lymphoma or skin cancer (melanoma cells) were placed for the experiment.

[0064] [Experiment on induction of apoptosis / necrosis of pathogenic cells (Jurkat T cells) of cutaneous lymphoma] Jurkat T cells were cultured at 37 °C in an environment of 5% CO₂ for 48 hours using a cell growth medium (RPMI1640 + 10% FBS). The proliferated Jurkat T cells were washed and replaced with PBS medium in 36 petri dishes. Using the apparatus shown in Figure 21, ultraviolet light was irradiated onto the pathogenic cells in the petri dishes using the ultraviolet light-emitting diodes at 340 nm, 365 nm, and 385 nm. The irradiation conditions are shown in Table 1. 2 The proliferated Jurkat T cells were washed and replaced with PBS medium in 36 petri dishes. Using the apparatus shown in Figure 21, ultraviolet light was irradiated onto the pathogenic cells in the petri dishes using the ultraviolet light-emitting diodes at 340 nm, 365 nm, and 385 nm. The irradiation conditions are shown in Table 1.

[0065]

Table 1

[0066] Note that due to the difference in the ultraviolet wavelength, the luminous efficiency of the ultraviolet light-emitting diode is different. Therefore, in order to make the irradiation intensity constant, the irradiation distance to the pathogenic cells was adjusted. As a result, the irradiation intensity, total irradiation dose, and irradiation time in Table 1 were made the same for all three wavelengths.

[0067] The pathogenic cells after ultraviolet irradiation were cultured at 37 °C in an environment of 5% CO₂ for 24 hours using a cell growth medium (RPMI1640 + 10% FBS). For the pathogenic cells in each petri dish after culture, staining was performed with the staining reagent Annexin V and the staining reagent PI, and then flow cytometry (FACS) analysis was performed using a flow cytometer device. If the Jurkat T cells are in a normal state without inducing apoptosis, membrane phospholipids (phosphatidylserine PS) exist inside the cell membrane and there is no damage to the cell membrane. Therefore, the reagent PI is not taken into the cell and does not bind to the nuclear DNA. However, when apoptosis induction occurs in the pathogenic cells, apoptotic cells and necrotic cells are stained with both the staining reagent Annexin V and the staining reagent PI. Therefore, quantitative analysis of apoptotic cells and necrotic cells can be performed by flow cytometry. 2 The pathogenic cells after ultraviolet irradiation were cultured at 37 °C in an environment of 5% CO₂ for 24 hours using a cell growth medium (RPMI1640 + 10% FBS). For the pathogenic cells in each petri dish after culture, staining was performed with the staining reagent Annexin V and the staining reagent PI, and then flow cytometry (FACS) analysis was performed using a flow cytometer device. If the Jurkat T cells are in a normal state without inducing apoptosis, membrane phospholipids (phosphatidylserine PS) exist inside the cell membrane and there is no damage to the cell membrane. Therefore, the reagent PI is not taken into the cell and does not bind to the nuclear DNA. However, when apoptosis induction occurs in the pathogenic cells, apoptotic cells and necrotic cells are stained with both the staining reagent Annexin V and the staining reagent PI. Therefore, quantitative analysis of apoptotic cells and necrotic cells can be performed by flow cytometry.

[0068] Figure 22 shows, at each wavelength of 340 nm, 365 nm, and 385 nm, the total irradiation dose of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm2 It is a graph showing the results of flow cytometry analysis indicating the densities of viable cells, apoptosis-induced cells, and necrosis-induced cells of pathogenic cells in each case irradiated. At any wavelength, as the total irradiation dose increased, the apoptosis-induced cells increased, but the necrosis-induced cells hardly increased. Also, the shorter the wavelength, the fewer the final viable cells. Figure 23 shows, at each wavelength of 340 nm, 365 nm, and 385 nm, the total irradiation doses of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2 and is a graph showing the ratio (%) of viable cells of pathogenic cells in each case irradiated (Tukey-Kramer test, p < 0.05, n = 3). As the total irradiation dose increased, and also the shorter the wavelength, the fewer the final viable cells. Figure 24 shows, at each wavelength of 340 nm, 365 nm, and 385 nm, the total irradiation doses of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2 and is a graph showing the ratio (%) of apoptosis-induced cells of pathogenic cells in each case irradiated (Tukey-Kramer test, p < 0.05, n = 3). At 10 J / cm 2 it was 60% or more, at 20 J / cm 2 it was 70% or more, and at 30 J / cm 2 80% or more of the cells were induced to apoptosis. The shorter the wavelength, the higher the ratio of apoptosis induction. Figure 25 shows, at each wavelength of 340 nm, 365 nm, and 385 nm, the total irradiation doses of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2 and is a graph showing the ratio (%) of necrosis-induced cells of pathogenic cells in each case irradiated (Tukey-Kramer test, p < 0.05, n = 3). From the control to 30 J / cm 2Until reaching this point, the ratio of necrotic cells was 2% or less in all cases. No particular influence of the difference in total irradiation dose and wavelength on necrosis induction was observed either.

[0069] As shown in FIGS. 22 to 25, in the case of leukemia cells (Jurkat T cells), which are floating cells, apoptosis induction was found to be highest at 97% in the case of a peak wavelength of 340 nm × 30 J / cm 2 On the other hand, necrosis induction occurred in only 2% or less even in the case of a peak wavelength of 340 nm × 30 J / cm 2

[0070] [Apoptosis and Necrosis Induction Experiments on Skin Cancer (Melanoma Cells)] Melanoma cells were cultured for 48 hours at 37°C in an environment of CO 2 : 5% using a cell growth medium (RPMI1640 + 10% FBS). The proliferated melanoma cells were washed and replaced into the PBS medium in 36 petri dishes. Using the apparatus shown in FIG. 21, ultraviolet light-emitting diodes with wavelengths of 340 nm, 365 nm, and 385 nm were used to irradiate the pathogenic cells in the petri dishes with ultraviolet light. The irradiation conditions were the same as in Table 1.

[0071] The pathogenic cells after ultraviolet irradiation were cultured for 48 hours at 37°C in an environment of CO 2 : 5% using a cell growth medium (RPMI1640 + 10% FBS). After culturing, the melanoma cells in each petri dish were stained with the staining reagent Annexin V and the staining reagent PI, and then flow cytometry (FACS) analysis was performed using a flow cytometer device.

[0072] FIG. 26 shows, at each wavelength of 340 nm, 365 nm, and 385 nm, a total irradiation dose of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2 ​It is a graph showing the results of flow cytometry analysis indicating the density of viable cells, apoptosis-induced cells, and necrosis-induced cells of melanoma cells in each case irradiated. In any wavelength, as the total irradiation dose increased, the apoptosis-induced cells increased, but the necrosis-induced cells hardly increased. Among the three wavelengths, the apoptosis-inducing effect was high at 340 nm and 365 nm, and it was confirmed that the apoptosis-inducing effect on melanoma cells was particularly high at 365 nm. Thus, it was confirmed that the absorption rate of ultraviolet light varies depending on the wavelength for different types of cancer.

[0073] Figure 27 is a graph showing the ratio (%) of viable cells of melanoma cells in each case irradiated at each wavelength of 340 nm, 365 nm, and 385 nm with a total irradiation dose of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2 (Tukey-Kramer test, p < 0.05, n = 3). When the total irradiation dose reached 30 J / cm 2 , the survival rate significantly decreased in the cases of 340 nm and 365 nm. Figure 28 is a graph showing the ratio (%) of apoptosis-induced cells of melanoma cells in each case irradiated at each wavelength of 340 nm, 365 nm, and 385 nm with a total irradiation dose of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2 (Tukey-Kramer test, p < 0.05, n = 3). When the total irradiation dose reached 30 J / cm 2 , the ratio of apoptosis-induced cells reached nearly 100% in the cases of 340 nm and 365 nm. Figure 29 is a graph showing the ratio (%) of necrosis-induced cells of melanoma cells in each case irradiated at each wavelength of 340 nm, 365 nm, and 385 nm with a total irradiation dose of 0 (control), 10 J / cm 2 , 20 J / cm 2 , 30 J / cm 2A graph showing the ratio (%) of cells with necrosis induced in melanoma cells in each case irradiated (Tukey-Kramer test, p<0.05, n = 3). It was 5 - 6% in the control, but at 10 to 30 J / cm 2 under the conditions, the ratio of cells with necrosis induced was about 1% or less in all cases. No particular influence of the difference in total irradiation dose and wavelength on necrosis induction was observed among these.

[0074] As shown in FIGS. 26 to 29, in the case of adherent cells of malignant melanoma (skin cancer), apoptosis induction of about 95 - 98% was shown at peak wavelengths of 340 nm and 365 nm at 30 J / cm 2 . In particular, it was confirmed that the apoptosis induction effect on melanoma cells was 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, it was found that ultraviolet light in a specific wavelength range has a high effect of inducing apoptosis in cancer cells and suppresses necrosis induction. Also, it was found that the effective peak wavelength and total irradiation dose differ depending on the type of cancer cell.

[0076] [Ultraviolet irradiation experiment on pathogenic cells of colorectal cancer, gastric cancer, and breast cancer] An ultraviolet irradiation experiment was conducted using pathogenic cells of human-derived colorectal cancer, gastric cancer, and breast cancer. Assuming the actual situation, tumors (spheroids) were created with each pathogenic cell. 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 at 37°C in an environment of CO 2 :5% using a cell growth medium (RPMI1640 + 10% FBS) to create tumors (spheroids). FIGS. 30(a) to (c) are photographs of each cell after culture in a petri dish, and FIGS. 30(d) to (f) are microscope photographs (40 times magnification) of those cells.

[0078] Using the apparatus shown in Fig. 21 and a 365-nm ultraviolet light-emitting diode, ultraviolet light was irradiated onto tumors of colorectal cancer, gastric cancer, and breast cancer in a petri dish. The irradiation conditions were a total irradiation dose of 0 (control) and a total irradiation dose of 30 J / cm 2 as follows. After irradiation, the tumor cells were further cultured in a cell growth medium (RPMI 1640 + 10% FBS) at 37 °C in an environment of CO 2 : 5% for 24 hours. The tumor was taken out of the petri dish and the cells were dissociated. The dissociated cells were counted using a hemocytometer to count live cells and apoptosis-induced dead cells, and compared with non-irradiated (control) samples.

[0079] Figs. 31(a) to (c) are graphs showing the ratio of live cells to dead cells in the case of non-irradiated (control) colorectal cancer cells (E-GFP), gastric cancer cells (Nawa (N+0)), and breast cancer cells (MCF-7), and Figs. 31(d) to (f) are graphs showing the ratio of live cells to apoptosis-induced dead cells after ultraviolet irradiation of 30 J / cm 2 respectively.

[0080] As shown in Fig. 31, it was found that apoptosis (cell death) induction occurred in the cells given a total irradiation dose of 30 J / cm 2 compared to non-ultraviolet irradiation (control). When comparing the irradiated colorectal cancer cells, gastric cancer cells, and breast cancer cells with a total irradiation dose of 30 J / cm 2 , it was found that colorectal cancer cells were more likely to induce apoptosis. On the other hand, for gastric cancer cells and breast cancer cells, it was not that 365 nm had no effect, but it was estimated that a total irradiation dose higher than the current experimental condition of 30 J / cm 2 was required. From these experimental results, it was found that the in-vivo implanted ultraviolet irradiation device is effective for cancer treatment by obtaining a sufficient total irradiation dose.

[0081] [Investigation of the effects of ultraviolet light (365 nm) on human dermal fibroblasts] To confirm that normal cells do not develop abnormalities when human skin fibroblasts that are not cancer cells are irradiated with ultraviolet light, the following experiment was conducted. Human skin fibroblasts were cultured for 72 hours at 37 °C in an environment with 5% CO 2 2 using cell growth medium (MEMα + 10% FBS). The proliferated human skin fibroblasts were washed and transferred to PBS medium in 15 petri dishes. Using the apparatus shown in Figure 21, a 365 nm ultraviolet light-emitting diode was used to irradiate the cells in the petri dishes with ultraviolet light. The irradiation conditions are shown in Table 2. Note that sham irradiation refers to a condition where the total irradiation dose is 30 J / cm 2 2 for the same time (16.6 min.) at room temperature without irradiating with ultraviolet light, with PBS medium added. From this condition, the effect of the PBS medium on the cells was investigated.

[0082]

Table 2

[0083] After ultraviolet irradiation, the cells were cultured for 72 hours at 37 °C in an environment with 5% CO 2 2 using cell growth medium (MEMα + 10% FBS). The cells in each petri dish after culturing were stained with the staining reagent Acridine Orange / Propidium Iodide Stain and then analyzed using an automatic fluorescence cell counter.

[0084] Figure 32 is a graph showing the ratio (%) of live cells in each sample with a total ultraviolet irradiation dose of 0 (control), sham irradiation, 10, 20, 30 (J / cm 2 2). The survival rate was nearly 100% in all cases. Figure 33 is a graph showing the ratio (%) of dead cells in each sample with a total ultraviolet irradiation dose of 0 (control), sham irradiation, 10, 20, 30 (J / cm 2 2). The mortality rate was as low as about 2 - 3% in all cases. Figures 34(a) - (e) are graphs showing the ratio (%) of dead cells in each sample with a total ultraviolet irradiation dose of 0 (control), sham irradiation, 10, 20, 30 (J / cm 2) are optical microscope photographs (100× magnification) of human dermal fibroblasts in each sample thus prepared. No particular differences were observed among them.

[0085] As shown in FIGS. 32 to 34, no significant difference was observed when comparing the control with the simulated irradiation. Therefore, it was found that the PBS medium did not have an adverse effect on human dermal fibroblasts. Also, compared with the control, ultraviolet irradiation at total irradiation doses of 10, 20, and 30 J / cm 2 was found not to have an adverse effect on human dermal fibroblasts. Even in the case of a maximum total irradiation dose of 30 J / cm 2 , the cell death was only about 3%. From these results, it was found that the ultraviolet rays emitted from the implantable ultraviolet irradiation device hardly have an adverse effect on healthy cells.

[0086] FIGS. 35 and 36 are photographs of the implantable ultraviolet irradiation device prototyped by the present inventors. Despite its small size of 4.8 mm in diameter × 12 mm in total length, the ultraviolet light-emitting diode (365 nm) was able to emit light upon receiving the alternating magnetic flux (300 kHz) from the power transmission coil.

Industrial Applicability

[0087] According to the implantable ultraviolet irradiation device of the present invention, the implantable ultraviolet irradiation device is implanted into the living body at a position where cancer cells can be irradiated with the ultraviolet rays emitted from the ultraviolet light-emitting element, power is generated in the power receiving coil by a wireless power supply device from outside the body, and ultraviolet rays are generated from the ultraviolet light-emitting element by this power and irradiated onto the cancer cells. Thereby, apoptosis can be highly induced in cancer cells, and by suppressing the induction of necrosis, minimally invasive cancer treatment with few side effects such as inflammation can be performed with less burden on the patient. Therefore, the present invention can be industrially utilized.

Explanation of Reference Numerals

[0088] 1 Implantable ultraviolet irradiation device 2 Power 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 Third Ultraviolet Light Emitting Element 8 Support 10 Housing 10A Housing Body 10B Lens 10C End 10D Bending Portion 12 Rectifier Circuit 14 Control Circuit 16 Pulse Control Circuit 20 Normal Cells 22 Skin 24 Cancer Cells L Ultraviolet Light 30 Compress Bandage 31 Power Transmission Coil 32 Cord 34 Power Transmission Unit 36 Battery 38 Control Circuit 40 Control Panel 42 Diode 43 Switching Circuit 50 Insertion Fixture 51 Body 52 Needle 54 Blade Tip 56 Opening 58 Shaft 59 Slit 60 Knob 62 Position Measuring Unit 64 Monitor 70 Withdrawal Fixture 71 Body 72 Needle 74 Blade Tip 76 Opening 78 Tube 79 Locking Claw 80 Knob 82 Set Screw

Claims

1. A power receiving coil for receiving wireless power supply, an ultraviolet light emitting element that emits ultraviolet light by the power generated by the power receiving coil, and a housing that holds the power receiving coil and the ultraviolet light emitting element in a state where the ultraviolet light emitted by the ultraviolet light emitting element can be emitted to the outside. The ultraviolet light emitting element is a bio-implantable ultraviolet irradiation device having a peak of the emission wavelength between 340 nm and 385 nm, and is provided with a wireless power supply device for wirelessly supplying power to the power receiving coil from outside the body, wherein the wireless power supply device is a power supply method of any one of an electromagnetic induction method, a magnetic field resonance type electromagnetic induction method, and an electromagnetic wave method, The wireless power supply device wirelessly supplies power to the power receiving coil so that the total irradiation dose of the ultraviolet rays from the ultraviolet light emitting element is 10 to 30 J / cm 2 A body-implanted ultraviolet irradiation system, characterized in that wireless power supply is performed to the power receiving coil so as to achieve this.

2. The bio-implantable ultraviolet irradiation system according to claim 1, wherein the housing is formed of a flexible material, and the bio-implantable ultraviolet irradiation device is bendable at a middle portion in the longitudinal direction of the housing.

3. The bio-implantable ultraviolet irradiation system according to claim 1 or 2, wherein the housing is formed of an amorphous fluororesin and has a cylindrical shape with both ends sealed, and the outer diameter of the housing is 2.9 mm or less.

4. The bio-implantable ultraviolet irradiation system according to claim 1 or 2, wherein a plurality of ultraviolet light emitting elements that generate ultraviolet light having different emission wavelengths are arranged in the housing, and a switching circuit is provided for selecting any one of the ultraviolet light emitting elements and supplying the power generated by the power receiving coil.

5. The bio-implantable ultraviolet irradiation system according to claim 1 or 2, wherein the tip of the bio-implantable ultraviolet irradiation device is pointed in a conical shape or a pyramidal shape, and the ultraviolet light from the ultraviolet light emitting element is emitted from the pointed tip.

Citation Information

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