JP5186697B2 - In vivo cell stimulator - Google Patents

Description

  The present invention relates to an in-vivo cell stimulation apparatus for stimulating elements contained in cells in a living body by the action of electromagnetic waves.

  Conventionally, local therapies that are less invasive to the whole body and less burden on the body have been used for cancer treatment. Typically, local therapy includes radiation therapy (Non-patent Document 1).

National Cancer Center Cancer Control Information Center Cancer Information Service website, http://ganjoho.ncc.go.jp/pub/med_info/treatment/010706.html

  Radiation therapy irradiates cancer cells with radiation, stimulates (damages) the genes (DNA) in the cancer cells, loses proliferation ability, or enhances apoptosis to cause cancer cells to die (cancer cells) This radiation therapy cures cancer and alleviates symptoms such as pain due to increased cancer. Here, the term “radiation” is a generic term for a substance that propagates energy in the form of a wave or particles in a space or substance, and radiation is broadly divided into two types: electromagnetic waves and particle beams. Electromagnetic waves include X-rays and gamma rays, and particle beams include electron, particle radiation such as protons and heavy particles (heavy ions).

  In the following, therapies and treatments using particle beams as radiation are specifically referred to as particle beam therapy and particle beam treatments, and therapies and treatments using electromagnetic waves such as X-rays and gamma rays as radiation are particularly radiotherapy, It shall be called radiation therapy. In addition, the above-mentioned “stimulating (stimulating)” refers to physical and chemical actions that occur according to the magnitude of the product of the intensity of radiation and the application time (stimulus magnitude). It refers to physically fragmenting a gene (DNA) in cancer cells. Hereinafter, in this specification, the term “provides stimulation (damage)” is used in this sense.

  Radiation therapy methods include external radiation methods that emit radiation from outside the body, and sealed brachytherapy (internal radiation method) in which radiation sources are inserted directly into body tissues, esophagus, and cavities such as the uterus. However, at present, the external irradiation method is the mainstream.

  When performing radiation therapy, generally, a treatment plan is made regarding which part of radiation, which direction, how much, and how many times it is to be treated. At this time, using a simulator or the like, the direction of radiation irradiation is examined so that a sufficient amount of radiation hits the cancer cells and does not hit the normal tissues around the cancer cells. In many cases, cancer cells are irradiated with radiation from one direction, but there are cases where radiation is irradiated from several directions.

  By the way, conventional radiation therapy using electromagnetic waves such as X-rays and gamma rays has less burden on the body compared to systemic therapy such as anticancer drug treatment, but local radiation irradiation to the cancer affected area is difficult, and radiation is cancerous. Since it hits the normal tissue around the cells, the burden on the body was still large. In particle beam therapy using particle beam as radiation, the particle beam has little effect on normal tissues around cancer cells and the burden on the body is light, but large-scale and high-speed accelerators such as cyclotron and synchrotron Expensive devices were necessary, and it was difficult to spread particle beam therapy to the terminal medical facilities.

  The present invention has been made in view of such problems, and an object of the present invention is to provide an in vivo cell stimulating device capable of performing local treatment with a compact and inexpensive device.

  The in vivo cell stimulating device of the present invention is an electromagnetic wave having a fundamental frequency of a frequency equal to the inverse of the relaxation time of a dielectric substance contained in a predetermined element among a plurality of elements constituting a predetermined cell in the living body. Electromagnetic wave generating means for generating, and convergent irradiating means for convergently irradiating an electromagnetic wave output from the electromagnetic wave generating means to a minute region including predetermined cells in the living body.

  The fundamental frequency of the electromagnetic wave output from the electromagnetic wave generating means is, for example, not less than 500 MHz and not more than 10 GHz. Here, the intensity of the fundamental frequency component contained in the electromagnetic wave generated by the electromagnetic wave generating means is small enough not to stimulate the dielectric material, and when the fundamental frequency component is converged to a minute region by the convergent irradiation means, The intensity of the fundamental frequency component in the minute region is preferably large enough to stimulate the dielectric material. Further, the electromagnetic wave output from the electromagnetic wave generating means preferably does not contain unnecessary components such as subharmonic, non-harmonic, residual FM, and SSB phase noise, but if these unnecessary components are included, The strength of these unnecessary components is not only small enough not to stimulate the dielectric material, but also when the unnecessary components are converged to the minute region by the convergence irradiation means, It is preferred that the strength be small enough not to irritate the dielectric material.

  In addition, the above-mentioned “elements constituting a predetermined cell in a living body” are, for example, the nucleus, nucleolus, microtubule, ribosome, endoplasmic reticulum, Golgi apparatus, lysosome, centrosome, secretory granule, and mitochondria, “Dielectric substance contained in an element constituting a predetermined cell in a living body” is, for example, DNA, RNA, or protein.

  In the in vivo cell stimulating device of the present invention, an electromagnetic wave having a fundamental frequency at a frequency equal to the reciprocal of the relaxation time of the dielectric substance contained in the predetermined element among the elements constituting the predetermined cell in the living body is generated as an electromagnetic wave. The electromagnetic wave generated from the means is converged and irradiated to a minute region including predetermined cells in the living body by the convergent irradiation means. As a result, only a minute region becomes a strong electromagnetic field, and therefore, only elements existing in the minute region among elements constituting a predetermined cell in a living body including a dielectric substance having a relaxation time equal to the inverse of the fundamental frequency are included. Selective stimulation from electromagnetic waves.

  According to the in vivo cell stimulating device of the present invention, an electromagnetic wave having a fundamental frequency of a frequency equal to the inverse of the relaxation time of the dielectric substance contained in the predetermined element among the elements constituting the predetermined cell in the living body. Since a minute area including a predetermined cell in a living body is convergently irradiated, the minute area among elements constituting the predetermined cell in the living body including a dielectric substance having a relaxation time equal to the inverse of the fundamental frequency. Stimulation by electromagnetic waves can be selectively given only to the elements present in. Thus, for example, when cancer cells are present in a minute region, it is possible to stimulate cancer cells existing in the minute region without stimulating cells existing around the minute region. Therefore, local treatment is possible. Further, in the present cell stimulation apparatus, the convergent irradiation means is used to converge and radiate the electromagnetic wave output from the electromagnetic wave generating means to the minute area, so that the power required in the minute area is output from the electromagnetic wave generating means. Since it is not necessary, it does not become a large size like an apparatus used in particle beam therapy, and can be downsized to a size of a table top. Therefore, local treatment can be performed with a compact and inexpensive device.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

  FIG. 1 shows a schematic configuration of an in-vivo cell stimulating device 1 according to an embodiment of the present invention, and FIG. 2 schematically shows an enlarged internal configuration of the electromagnetic wave generator 10 of FIG. is there. This in-vivo cell stimulating device 1 includes an electromagnetic wave generator 10 (electromagnetic wave generating means), a coaxial line 20, a monopole antenna 30, a spheroid reflector 40, and a water tank 50. The monopole antenna 30 and the spheroid reflector 40 correspond to a specific example of “convergent irradiating means” of the present invention. The water tank 50 is filled with a liquid such as water, and the monopole antenna 30, the spheroid reflector 40 and the living body 60 are immersed in the liquid.

  Here, the living body 60 is configured to include various types of in-vivo cells 2, and has, for example, an affected part 60A in which cancer cells are present. Each in-vivo cell 2 includes intracellular components such as a nucleus, a nucleolus, a microtubule, a ribosome, an endoplasmic reticulum, a Golgi apparatus, a lysosome, a centrosome, a secretory granule, and a mitochondria. The in-vivo cell 2 may be either an animal cell or a plant cell, and may or may not be covered with a cell wall. Further, some pre-processing may be performed or may not be performed.

  These intracellular components include dielectric substances such as nucleic acids such as DNA and RNA, and proteins. Here, the dielectric material has a specific relaxation time corresponding to its structure and constituent molecules, and has a specific resonance frequency corresponding to the size of this specific relaxation time. The resonance frequency of each dielectric substance varies depending on the type and size of the in-vivo cell 2, but is scattered in a range of approximately 1 MHz to 10 GHz.

  The electromagnetic wave generator 10 includes, for example, a so-called virtual cathode oscillation tube, and is formed by disposing a cathode 11 and an anode 12 in a vacuum tube 13 so as to face each other.

  The cathode 11 has, for example, a structure in which fine fibers are attached to the upper surface of a columnar metal provided in contact with the inner wall of the vacuum tube 13. The cathode 11 emits electrons from the upper surface of the cathode 11 (for example, fine fibers on the metal) by the action of an electric field generated between the anode 12 and the cathode 11 when a pulse high voltage is applied to the anode 12. It has become.

  The anode 12 is configured to include, for example, mesh-like stainless steel, and is provided through the side wall of the vacuum tube 13 and is fixed to the side wall of the vacuum tube 13 via an insulator 14 provided on the side wall of the vacuum tube 13. ing. The anode 12 emits electrons from the cathode 11 and accelerates the emitted electrons to a predetermined energy by the action of an electric field between the anode 12 and the cathode 11 generated when a pulse high voltage is applied to the anode 12. As a result, a high-density electron current is generated, and the electron current is passed through the back side of the anode 12 through a mesh gap, for example. The electrons that have passed through the anode 12 are decelerated due to space charge, and as a result, an electron pool (virtual cathode 15) is generated.

  The vacuum tube 13 is a waveguide made of copper, for example, and is connected to the ground. On the wall surface of the vacuum tube 13 in the radiation direction of the electromagnetic wave M, an extraction window 16 for taking out the electromagnetic wave M out of the vacuum tube 13 is provided. The extraction window 16 is made of, for example, quartz. A waveguide / coaxial converter 17 is attached to the extraction window 16, and the electromagnetic wave M extracted from the vacuum tube 13 is converted into, for example, a TEM mode by the waveguide / coaxial converter 17. The signal is output to the coaxial line 20.

  In this electromagnetic wave generator 10, once the virtual cathode 15 is generated, electrons reciprocate between the cathode 11 and the virtual cathode 13, and electromagnetic waves M are generated by this reciprocating motion. The frequency of the electromagnetic wave M is 1 GHz or more and 10 GHz or less, and can be controlled to some extent by the distance between the cathode 11 and the anode 12. That is, the electromagnetic wave generator 10 can generate the electromagnetic wave M within the range of the resonance frequency of each dielectric substance.

  The coaxial line 20 is a waveguide that propagates the electromagnetic wave M radiated from the electromagnetic wave generator 10 to the monopole antenna 30. One end of the coaxial line 20 is attached to the waveguide / coaxial converter 17, and the other end is connected to the monopole antenna 30.

  The monopole antenna 30 is disposed at the first focal point F1 of the spheroid reflector 40. The spheroid reflector 40 has two focal points (first focal point F1 and second focal point F2) on the rotational axis, and electromagnetic waves M radiated from the monopole antenna 30 disposed at the first focal point F1. Is reflected and converged to the second focal point F2. The electromagnetic wave M radiated from the monopole antenna 30 is reflected by the spheroid reflector 40 and converges to the second focal point F2 of the spheroid reflector. The reflecting surface of the spheroid reflecting mirror 40 is made of, for example, copper.

  In the present embodiment, it is assumed that the monopole antenna 30 and the spheroid reflector 40 are positioned using a predetermined method so that the affected part 60A of the living body 60 is disposed at the second focal point F2. .

  By the way, although the intensity | strength of the fundamental frequency component contained in the electromagnetic wave M emitted from the electromagnetic wave generator 10 is low to such an extent that the dielectric substance in the in-vivo cell 2 contained in the biological body 60 is not stimulated, When the fundamental frequency component is converged to the second focus F2 by the monopole antenna 30 and the spheroidal electromagnetic wave reflector 50, the intensity of the fundamental frequency component at the second focus F2 is high enough to stimulate the dielectric substance. It has become.

  The electromagnetic wave M emitted from the electromagnetic wave generator 10 preferably does not contain unnecessary components such as harmonics, subharmonics, non-harmonics, residual FM, and SSB phase noise. However, these unnecessary components are included. In this case, the strength of these unnecessary components is not only reduced to such an extent that the dielectric material is not stimulated, but the unnecessary components are secondly reduced by the monopole antenna 30 and the spheroid electromagnetic reflector 50. It is preferable that the intensity of the unnecessary component at the second focal point F2 when converged to the focal point F2 is low enough not to stimulate the dielectric substance. In other words, the electromagnetic wave M emitted from the electromagnetic wave generator 10 is an electromagnetic wave having a small frequency component other than the fundamental frequency component, and preferably has a feature that most of the input power is concentrated on the fundamental frequency.

  When most of the input power is concentrated in the fundamental frequency region as described above, it is not necessary to generate an electromagnetic wave with a large power by the electromagnetic wave generator 10 in order to stimulate intracellular components.

  In addition, since the irradiation time of the electromagnetic wave M onto the minute region F can be increased by increasing the number of cycles of the voltage (acceleration voltage) applied between the cathode 11 and the anode 12, the fundamental frequency and the application time are increased. And can be controlled independently. Thereby, since the magnitude | size of the stimulus which an intracellular component receives can be set arbitrarily, the stimulus according to the objective and a use can be given to an intracellular component.

  Here, the intensity of the electromagnetic wave M that does not stimulate the dielectric substance varies depending on the irradiation time of the electromagnetic wave M, and if the irradiation time is short, the dielectric substance is not stimulated even if the intensity of the electromagnetic wave M is large to some extent. On the contrary, even if the application time is long, if the intensity of the electromagnetic wave M is low to some extent, the dielectric substance is not stimulated. Accordingly, although the value varies somewhat depending on the type of the in vivo living body cell 2, the product of the intensity of the fundamental frequency component contained in the electromagnetic wave M in the minute region F and the irradiation time for convergently irradiating the minute region F with the electromagnetic wave M. Is set to be equal to or greater than a predetermined value, and the intensity and irradiation time of the electromagnetic wave M generated by the electromagnetic wave generator 10 are set.

  In the in-vivo cell stimulation apparatus 1 of the present embodiment, an electromagnetic wave having a fundamental frequency of a frequency equal to the inverse of the relaxation time of the dielectric substance contained in the predetermined element among the elements constituting the predetermined in-vivo cell 2. M is generated from the electromagnetic wave generator 10, and the electromagnetic wave M is converged and irradiated to the second focal point F2 where the affected part 60A exists by the monopole antenna 30 and the spheroid electromagnetic wave reflecting mirror 50. Thereby, since only the affected part 60A becomes a strong electromagnetic field, only elements existing in the affected part 60A among the elements constituting the predetermined in-vivo cell 2 including the dielectric substance having the relaxation time equal to the reciprocal of the fundamental frequency are included. Stimulation by the electromagnetic wave M can be selectively given. Thereby, for example, when cancer cells are present in the affected part 60A, the cancer cells existing in the affected part 60A are stimulated without stimulating the in vivo cells 2 existing around the affected part 60A. Therefore, local treatment is possible. Further, in the in vivo cell stimulation apparatus 1 of the present embodiment, the electromagnetic wave M output from the electromagnetic wave generator 10 is converged and irradiated to the second focal point F2 using the monopole antenna 30 and the spheroid electromagnetic wave reflecting mirror 50. Since the power required for the second focal point F2 does not need to be output from the electromagnetic wave generator 10, it does not become a large size like a device used in particle beam therapy, and is about a table top. The size can be reduced to the size of Therefore, local treatment can be performed with a compact and inexpensive device.

[Example]
Next, examples according to the above embodiment will be described.

  In this example, in order to estimate the proliferative ability of CHO (Chinese Hamster Ovary) cells, before CHO cells were irradiated with electromagnetic waves, a specific CHO cell was selected during DNA replication. BrdU (bromodeoxyuridine) was incorporated into the intracellular components. This BrdU can be detected by using a BrdU antibody, and by measuring the area of BrdU detected by this BrdU antibody, the area of the active reaction region of CHO cells can be known. By comparing with the area of the active reaction region detected when the CHO cells were grown without irradiating the CHO cells with any electromagnetic wave, the proliferation ability of the CHO cells can be estimated.

  In this embodiment, the in-vivo cell stimulating apparatus 1 has a voltage Vd applied between the cathode 11 and the anode 12 in the range from several tens kV to about 100 kV, as shown in FIG. 0. When changed for several seconds, an electromagnetic wave in the range of about 2 GHz to 3.5 GHz is generated from the electromagnetic wave generator 10, and as shown in FIG. 4, the intensity of the electromagnetic wave at the second focal point F2 at this time Has a characteristic of 15 MW at 3 GHz. That is, the in-vivo cell stimulating device 1 here applies an acceleration voltage in the range of about several tens of kV to about 100 kV between the cathode 11 and the anode 12 to provide a range of about 2 GHz to 3.5 GHz. The electromagnetic wave inside can be generated.

  First, as described above, before irradiating CHO cells with electromagnetic waves, in the DNA replication phase, BrdU is incorporated into a specific intracellular component (for example, nucleus 20) of the CHO cells, and the intracellular cells that have incorporated BrdU. After the four types of electromagnetic waves A to D shown in FIG. 5 are separately converged and irradiated to the microregion F including the CHO cells having the constituent elements, BrdU contained in the CHO cells is changed to BrdU after a while. It detected with the antibody and the area of the active reaction area | region was measured. In FIG. 5, the measured area of each active reaction region is divided by the area of the active reaction region detected when the CHO cells were grown without irradiating the CHO cells with electromagnetic waves at all (Comparative Example). The values obtained are shown.

  Here, the electromagnetic wave A in FIG. 5 is an electromagnetic wave having a fundamental frequency of 3.6 GHz and an intensity of 13 MW, and the electromagnetic wave B is an electromagnetic wave having a fundamental frequency of 3.6 GHz and an intensity of 10 MW. C is an electromagnetic wave having a fundamental frequency of 2.7 GHz and an intensity of 2 MW.

  From FIG. 5, when the electromagnetic wave B was converged and irradiated to the CHO cell, the active reaction region was the narrowest and was only about 0.1 as compared with the comparative example. That is, it can be said that when the electromagnetic wave B is convergently irradiated to the CHO cell, the proliferation ability of the CHO cell is suppressed to about 1/10. Therefore, it can be said that the CHO cells at this time were almost inactivated by exposure to the electromagnetic wave B. In other cases, since the active reaction region is about 0.4 at the maximum compared to the comparative example, the CHO cells can be generally inactivated by exposure to electromagnetic waves A, C, and D. I can say.

  While the present invention has been described with reference to the embodiment and examples, the present invention is not limited to these, and various modifications are possible.

  For example, in the above embodiment, the electromagnetic wave generator 10 is configured by a virtual cathode oscillation tube, but may be configured by, for example, a magnetron, a klystron, or the like.

It is a schematic block diagram of the in-vivo cell stimulation apparatus which concerns on one embodiment of this invention. It is a schematic block diagram of the electromagnetic wave generator of FIG. It is a wave form diagram for demonstrating the relationship between the acceleration voltage and fundamental frequency of the electromagnetic wave generator which concerns on an Example. It is a frequency spectrum figure of the electromagnetic waves output from the electromagnetic wave generator which concerns on an Example. It is a relationship figure for demonstrating the relationship between the inactivation rate of the CHO cell in an Example, and the fundamental frequency and power of electromagnetic waves.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Cell stimulator in a living body, 2 ... Cell, 10 ... Electromagnetic wave generator, 11 ... Cathode, 12 ... Anode, 13 ... Vacuum tube, 14 ... Insulator, 15 ... Virtual cathode, 16 ... Extraction window, 17 ... Waveguide -Coaxial conversion part, 20 ... Coaxial line, 30 ... Monopole antenna, 40 ... Spheroidal reflector, 50 ... Water tank, 60 ... Living body, 60A ... Affected part, F1 ... First focus, F2 ... Second focus, M ... Electromagnetic waves.

Claims (6)

Electromagnetic wave generating means for generating an electromagnetic wave having a fundamental frequency of a frequency equal to the inverse of the relaxation time of the dielectric substance contained in the predetermined element among the plurality of elements constituting the predetermined cell in the living body;
Convergent irradiating means for converging and irradiating the electromagnetic wave output from the electromagnetic wave generating means to a minute region including predetermined cells in the living body,
The fundamental frequency is 1 GHz or more and 10 GHz or less,
The intensity of the fundamental frequency component contained in the electromagnetic wave generated by the electromagnetic wave generating means is small enough not to stimulate the dielectric substance, and the electromagnetic wave generated by the electromagnetic wave generating means is converged on the micro area by the convergent irradiation means. An in- vivo cell stimulating device characterized in that the intensity of the fundamental frequency component in the minute region is high enough to stimulate the cells when it is applied. The intensity of the electromagnetic wave generated by the electromagnetic wave generating means so that the product of the intensity of the fundamental frequency component included in the electromagnetic wave in the minute area and the irradiation time for convergent irradiation of the electromagnetic wave on the minute area is a predetermined value or more, and The in vivo cell stimulation apparatus according to claim 1, wherein each of the irradiation times is set. The in-vivo cell stimulating device according to claim 1, wherein the predetermined cell in the living body is a cancer cell. The element that constitutes a predetermined cell in the living body is a nucleus, nucleolus, microtubule, ribosome, endoplasmic reticulum, Golgi apparatus, lysosome, centrosome, secretory granule, or mitochondria. The in-vivo cell stimulating device. The in vivo cell stimulating device according to claim 1, wherein the dielectric substance is DNA, RNA, or protein. The in vivo cell stimulation apparatus according to claim 1, wherein the convergent irradiation means includes a monopole antenna and a spheroid reflector.

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