CN113577562A - Alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells - Google Patents
Alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells Download PDFInfo
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Abstract
The invention relates to the field of medical equipment and discloses an alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells.A magnetic ring or a magnetic chain is wound on a metal coil, and a closed loop is formed between two ends of the metal coil and an alternating signal generating circuit; when in use, the carrier of the tumor cells which are dividing rapidly is positioned in the magnetic ring or the magnetic chain or on one side; a preset alternating current with the frequency of 30 kHz-300 kHz is loaded on the coil through the alternating signal generating circuit to generate a preset alternating magnetic field in the magnetic ring or the magnetic chain, and then a preset alternating electric field with the strength of 0.1V/cm-10V/cm is formed in the direction perpendicular to the magnetic ring or the magnetic chain, wherein the preset alternating electric field destroys or inhibits the rapidly dividing tumor cells in the carrier and does not act on normal cells. The device does not have an electrode, and when the device is used, the body can be placed in the magnetic ring or the magnetic chain or on one side of the magnetic ring or the magnetic chain without being tightly attached to the skin, so that the device can be worn or used for a long time, and the comfort level is high.
Description
Technical Field
The invention relates to the field of medical instruments, in particular to an alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells.
Background
It is well known that tumors, particularly malignant tumors or cancers, have uncontrolled, unlimited proliferation of cell division, rapid growth, low cell differentiation, and infiltration and diffusion (migration) compared to normal tissues.
As mentioned above, rapid growth of tumors (particularly malignant tumors) is often the result of relatively frequent cell division or proliferation as compared to normal tissue cells. The frequent cell division of cancer cells relative to normal cells is the basis for the effectiveness of existing cancer treatments, such as radiation therapy and the use of a wide variety of chemotherapeutic agents. Such treatments are based on the fact that cells undergoing division are more sensitive to radiation and chemotherapeutic agents than non-dividing cells. Because tumor cells divide more frequently than normal cells, it is possible to some extent to selectively damage or destroy tumor cells by radiation therapy and/or chemotherapy. The actual sensitivity of cells to radiation, therapeutic agents, etc. also depends on the specific characteristics of the different types of normal or malignant cell types. Thus, unfortunately, the sensitivity of tumor cells is not significantly higher than many types of normal tissue. This makes it less readily distinguishable between tumor cells and normal cells, and thus existing treatment protocols typical of cancer can also cause significant damage to normal cells, thereby limiting the therapeutic efficacy of such treatments. Furthermore, the inevitable damage to other tissues makes the treatment very damaging to the patient and the patient often cannot recover from an apparently successful treatment. Also, certain types of tumors are not sensitive at all to existing treatments.
Other methods for destroying cells exist that do not rely on radiation therapy or chemotherapy alone. For example, methods of destroying tumor cells using ultrasound or electricity may be used in place of conventional therapeutic methods. Electric fields and currents have been used for many years for medical purposes. Most commonly, an electric current is generated in the body of a human or animal by applying an electric field in the body of the human or animal by means of a pair of conductive electrodes between which a potential difference is maintained. These currents are either used to exert their special effect, i.e. to stimulate excitable tissues, or to generate heat by creating currents in the body, since the body can be equivalently resistive. Examples of the first type of application include: cardiac defibrillators, peripheral nerve and muscle stimulators, brain stimulators, and the like. Examples of the use of electric current for generating heat include: tumor resection, resection of malfunctioning heart or brain tissue, cauterization, relief of muscle rheumatalgia or other pain, and the like.
Other applications of electric fields for medical purposes include the use of high frequency oscillating fields emitted from sources emitting e.g. radio frequency electric waves or microwave sources directed to a region of interest of the body. In these examples, there is no electrical energy conduction between the source and the body; but rather energy is transferred to the body by radiation or induction. More particularly, the electrical energy generated by the source reaches the vicinity of the body via a conductor and is transmitted from this location to the human body through air or some other electrically insulating material.
In conventional electrical methods, electrical current is delivered to a target tissue region through electrodes placed in contact with the patient's body. The applied current will destroy substantially all cells in the vicinity of the target tissue. Thus, this type of electrical approach does not distinguish between different types of cells within the target tissue and results in destruction of both tumor and normal cells.
Application No. 200580048335.X, entitled apparatus for selectively destroying or inhibiting the growth of rapidly dividing tumor cells located within a target region of a patient, discloses that the apparatus comprises: at least two pairs of insulated electrodes (1620, 1630), wherein each electrode (1620, 1630) has a surface configured for placement against a patient's body; and an AC voltage source having at least two sets of outputs, wherein the at least two sets of outputs are phase shifted and are each electrically connected to one of the at least two pairs of insulated electrodes (1620, 1630); wherein the AC voltage source and the electrodes (1620, 1630) are configured such that when the electrodes (1620, 1630) are placed in close proximity to the patient's body, an AC electric field is applied into the patient's target region (1612) in a direction that is rotated relative to the target region (1612) due to a phase shift between at least two sets of outputs, the applied electric field having frequency and field strength characteristics such that the electric field (a) selectively destroys rapidly dividing tumor cells, and (b) leaves normal cells substantially unharmed. The device better distinguishes between dividing cells (including unicellular tissue) and non-dividing cells, and is capable of selectively destroying rapidly dividing tumor cells without substantially affecting normal cells or the body. However, when the device is used, the electrodes therein must be tightly adhered to the skin of the patient, which is not suitable for long-term use and has low use comfort. And the electrode has certain life, must regularly change, and use cost is extremely high.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the problems in the prior art, the invention provides an alternating electric field device for selectively destroying or inhibiting the mitosis of tumor cells, which can selectively destroy the tumor cells without basically influencing normal cells or a body.
The technical scheme is as follows: the invention provides an alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells, which comprises a closed magnetic ring or magnetic chain and at least one metal coil wound on the magnetic ring or the magnetic chain, wherein a closed loop is formed between two ends of the metal coil and an alternating signal generating circuit; the alternating signal generating circuit is any one or combination of the following: the sine wave generator comprises a constant-amplitude sine wave generator circuit, a reducing sine wave generator circuit, an amplifying sine wave generator circuit, a sine wave generator circuit with amplitude increasing and then reducing, and a sine wave circuit with frequency continuously changing between a maximum value and a minimum value; the inductance in each sine wave generator circuit is the metal coil; and loading a certain constant frequency with a current waveform of 30 kHz-300 kHz or a preset alternating current with continuously changed frequency on the metal coil through the alternating signal generating circuit, wherein the preset alternating current can enable a preset alternating magnetic field to be generated in the magnetic ring or the magnetic chain, and the preset alternating magnetic field can form a preset alternating electric field with the intensity of 0.1V/cm-10V/cm, which can destroy or inhibit the rapidly dividing tumor cells in the carrier and does not act on the normal cells, in the direction perpendicular to the magnetic ring or the magnetic chain.
Furthermore, the device also comprises a random/periodic signal generating circuit, an electric control switch is connected between the VDD power supply and the power supply input end of each alternating signal generating circuit, and an output signal of the random/periodic signal generating circuit is used for controlling the electric control switch. The random/periodic signal generating circuit may control the alternating signal generating circuit so as to divide the generated alternating signal into a plurality of series, and the time of occurrence of each series may be periodic, random or continuous.
Preferably, the constant-amplitude sine wave generator circuit is a clar wave oscillation circuit or a chaylor oscillation circuit, and the output current waveform of the preset alternating current is a continuous constant-amplitude sine wave, multiple groups of constant-amplitude sine waves with periodic time intervals, or multiple groups of constant-amplitude sine waves with random time intervals.
Preferably, an electronic control switch is connected between the Vdd power supply and the clar wave oscillation circuit or the schiler oscillation circuit, an input end of the electronic control switch is connected with an output end of the random/periodic signal generation circuit, and a current waveform of the output preset alternating current is a plurality of groups of sine waves with periodic time intervals or a plurality of groups of constant-amplitude sine waves with random time intervals.
Preferably, the constant-amplitude sine wave generator circuit mainly comprises a sawtooth wave generator and a voltage-controlled oscillator, wherein sawtooth wave voltage generated by the sawtooth wave generator controls the voltage-controlled oscillator, and the voltage-controlled oscillator is connected with an inductance coil; the output current waveform of the preset alternating current is similar to a frequency modulation continuous FMCW wave, a plurality of groups of FMCW waves with periodic time intervals or a plurality of groups of FMCW waves with random time intervals.
Preferably, the constant-amplitude sine wave generator circuit mainly comprises a triangular wave generator and a voltage-controlled oscillator, wherein the voltage-controlled oscillator is connected with an inductance coil; the triangular wave voltage generated by the triangular wave generator controls the voltage-controlled oscillator, and the output current waveform of the preset alternating current is similar to a frequency modulation continuous FMCW wave, multiple groups of FMCW waves with periodic time intervals or multiple groups of FMCW waves with random time intervals.
Preferably, the constant-amplitude sine wave generator circuit mainly comprises a sine wave generator and a voltage-controlled oscillator, wherein the voltage-controlled oscillator is connected with an inductance coil; the sine wave voltage generated by the sine wave generator controls the voltage-controlled oscillator, and the current waveform of the output preset alternating current is similar to a frequency modulation continuous FMCW wave, multiple groups of FMCW waves with periodic time intervals or multiple groups of FMCW waves with random time intervals.
Preferably, the amplitude-reduced sine wave generator circuit is an LC oscillator circuit, and the output current waveform of the preset alternating current is a continuous amplitude-reduced sine wave, a periodic time interval amplitude-reduced sine wave or multiple groups of random time intervals amplitude-reduced sine waves.
Preferably, the amplified sine wave generator circuit mainly comprises a high-frequency sine wave generator, a sawtooth wave generator and an analog multiplier circuit, and the analog multiplier circuit is connected with the inductance coil; and multiplying the high-frequency sine wave generated by the high-frequency sine wave circuit by the sawtooth wave generated by the sawtooth wave generator, wherein the output current waveform of the preset alternating current is a continuous amplification sine wave, multiple groups of amplification sine waves with periodic time intervals or multiple groups of amplification sine waves with random time intervals.
Preferably, the first increase and then decrease sine wave generator circuit mainly comprises a high-frequency sine wave generator, a low-frequency sine wave generator and an analog multiplier circuit, wherein the analog multiplier circuit is connected with the inductance coil; and multiplying the high-frequency sine wave generated by the high-frequency sine wave generator by the low-frequency sine wave generated by the low-frequency sine wave generator, wherein the output current waveform of the preset alternating current is that the amplitude is increased and then reduced by a continuous sine wave, the amplitudes of a plurality of groups of periodic time intervals are increased and then reduced by a sine wave or the amplitudes of a plurality of groups of random time intervals are increased and then reduced by a sine wave.
Preferably, the first increase and then decrease sine wave generator circuit mainly comprises a high-frequency sine wave generator, a triangular wave generator and an analog multiplier circuit, wherein the analog multiplier circuit is connected with the inductance coil; and multiplying the high-frequency sine wave generated by the high-frequency sine wave generator by the triangular wave generated by the triangular wave generator, wherein the output current waveform of the preset alternating current is a sine wave with amplitude increased and then reduced continuously, a sine wave with amplitude increased and then reduced at a plurality of groups of periodic time intervals or a randomly amplified sine wave with a plurality of groups of random time intervals.
The working principle is as follows: when the device is used, a carrier of cells which are rapidly split is placed in a magnetic ring or a magnetic chain or on one side of the magnetic ring or the magnetic chain, a specific alternating signal generating circuit is electrified to generate alternating current with the frequency of 30 kHz-300 kHz and random amplitude, when the alternating current is output to a coil, an alternating magnetic field is generated in the magnetic ring or the magnetic chain, the direction of the alternating magnetic field is consistent with the direction of the magnetic ring or the magnetic chain, and a closed loop is formed like the magnetic ring or the magnetic chain. The alternating magnetic field forms an alternating electric field with the strength of 0.1V/cm-10V/cm in the vertical direction, namely the direction vertical to the magnetic ring or the magnetic linkage plane. Since cells are more susceptible to damage from alternating electric fields having specific frequency and electric field strength characteristics when they are rapidly dividing. Therefore, when the carrier of the rapidly dividing tumor cells is positioned in the alternating electric field, the rapidly dividing tumor cells positioned in the alternating electric field of the magnetic ring or the magnetic chain are influenced by the alternating electric field which has the same frequency as the alternating current in the coil and has the same trend strength of 0.1V/cm-10V/cm, the rapidly dividing tumor cells can be selectively destroyed by the alternating electric field with the specific frequency and the electric field strength characteristic for a period of time, and the normal cells cannot be damaged because of insensitivity to the alternating electric field with the specific frequency and the electric field strength characteristic. This selectively destroys rapidly dividing cells like tumor cells without damaging normal cells.
Has the advantages that: when the device is used, the carrier of the rapidly dividing tumor cells is directly placed in a magnetic ring or a magnetic chain or on one side, the device does not have an electrode, is not required to be tightly attached to the skin for use, can be worn or used for a long time, and has higher comfort level; can selectively destroy a rapidly dividing cell or body without substantially affecting normal cells or bodies.
Drawings
FIG. 1 is a schematic diagram of an apparatus for selectively destroying or inhibiting rapid division of tumor cells, wherein an alternating current signal is input to an inductive coil by an alternating signal generating circuit powered by VDD;
FIG. 2 is a schematic diagram of a switching power supply circuit providing a supply voltage VDD for subsequent circuits;
FIG. 3 is a schematic diagram of the structure of an apparatus for selectively destroying or inhibiting rapid division of tumor cells, wherein a damped sinusoidal current signal is passed through an inductor at fixed and random time intervals;
FIG. 4 is a constant amplitude sine wave generator circuit-a Clara wave oscillator circuit (modified capacitance three-point oscillator circuit) for generating a continuous constant amplitude sine wave;
FIG. 5 is a Krah wave oscillator circuit (modified capacitance three-point oscillator circuit) as a constant amplitude sine wave generator circuit for generating periodic or random time intervals;
FIG. 6 is a constant amplitude sine wave generator circuit for generating a continuous constant amplitude sine wave-a Schiller oscillator circuit (modified capacitive three-point oscillator circuit);
FIG. 7 is a constant amplitude sine wave generator circuit for generating periodic or random time intervals-a Schiller oscillator circuit (modified capacitive three-point oscillator circuit);
FIG. 8 shows a current waveform of a continuous constant-amplitude sine wave with the same frequency and amplitude;
FIG. 9 is a constant-amplitude sine wave with a current waveform of multiple groups of periodic time intervals, wherein each group of periodic sine waves has the same frequency, amplitude and duration, and idle time intervals between two adjacent groups of periodic sine waves are the same;
FIG. 10 is a diagram showing current waveforms of multiple groups of constant-amplitude sine waves with the same frequency, the same amplitude, and random duration of each group of random sine waves, and with the same or random idle time intervals between two adjacent groups of random sine waves;
fig. 11 shows that the current waveforms are amplitude-reduced sine waves with the same frequency, the same initial amplitude, the same damping attenuation coefficient of the amplitude, and the same idle time interval between two adjacent groups of periodic amplitude-reduced sine waves at multiple groups of periodic time intervals;
FIG. 12 is one of the alternating signal generating circuits of FIG. 1 that generates a damped sine wave signal at periodic or random time intervals;
fig. 13 shows a plurality of groups of random time intervals of amplitude-reduced sine waves with current waveforms, wherein the frequency of each group of amplitude-reduced sine waves is the same, the initial amplitudes of the sine waves are the same or different, the attenuation coefficients are the same or different, and the idle time intervals between two adjacent groups of random amplitude-reduced sine waves are random;
FIG. 14 is a graph showing current waveforms of multiple groups of amplified sine waves with the same frequency and gradually increased amplitude for each group of sine waves, and the idle time intervals between two adjacent groups of sine waves are the same or random;
FIG. 15 is a circuit for generating the sets of randomly time spaced amplified sine wave current waveforms of FIG. 14;
FIG. 16 is a schematic diagram of the circuit of FIG. 15 producing sets of randomly time spaced amplified sine wave current waveforms of FIG. 14;
FIG. 17 shows a current waveform in which each group of sine waves has the same frequency, and the amplitude of each group of sine waves is gradually increased and then decreased;
FIG. 18 is one of the circuits for generating the sine wave current waveforms of FIG. 17 with the amplitude increasing and then decreasing for the sets of random time intervals;
FIG. 19 is a schematic diagram of the circuit of FIG. 18 producing sine wave current waveforms of the sets of random time intervals of FIG. 17 with increasing amplitude and then decreasing amplitude;
FIG. 20 is another circuit for generating the sine wave current waveforms of FIG. 17 with the amplitude increased and then decreased for the sets of random time intervals;
FIG. 21 is a schematic diagram of the circuit of FIG. 20 producing sine wave current waveforms of the sets of random time intervals of FIG. 17 with increasing amplitude and then decreasing amplitude;
FIG. 22 is a similar frequency modulated continuous FMCW wave with a current waveform that increases linearly in frequency over the pulse duration;
FIG. 23 is one of the circuits that produces the continuous FMCW wave current waveform of FIG. 22;
FIG. 24 is a similar frequency modulated continuous FMCW wave in which the current waveform is linearly increasing in frequency for the duration of the pulse, followed by a linear decrease in frequency;
FIG. 25 is a circuit for generating the continuous FMCW wave current waveform of FIG. 24;
FIG. 26 is a frequency modulated continuous FMCW wave in which the frequency of the current waveform varies in a sinusoidal manner during a cycle;
FIG. 27 is a circuit for generating the continuous FMCW wave current waveform of FIG. 26;
FIG. 28 is a schematic view of the structure of a bracelet, foot ring, neck ring or waist band for selectively destroying or inhibiting the rapid division of tumor cells in embodiment 2-the wearing component is a closed ring structure;
FIG. 29 is a schematic view of the structure of a bracelet, foot ring, neck ring or waist band for selectively destroying or inhibiting the rapid division of tumor cells in embodiment 2, wherein the wearing component is in a non-closed ring structure;
FIG. 30 is a schematic structural view of a bracelet, a foot ring, a neck ring or a waist band for selectively destroying or inhibiting tumor cell division in accordance with embodiment 3;
FIG. 31 is a schematic structural view of a bracelet, a foot ring, a neck ring or a waistband for selectively destroying or inhibiting tumor cell division in embodiment 4;
FIG. 32 is a schematic structural view of a bracelet, a foot ring, a neck ring or a waist band for selectively destroying or inhibiting tumor cell division in accordance with embodiment 5;
FIG. 33 is a schematic view of the vest structure used for selectively destroying or inhibiting the rapid division of tumor cells in embodiment 6;
FIG. 34 is a schematic representation of a brassiere according to embodiment 7 for selectively destroying or inhibiting rapid division of tumor cells;
FIG. 35 is a schematic view of the structure of a cap for selectively destroying or inhibiting the rapid division of tumor cells in embodiment 8;
FIG. 36 is a schematic view of the structure of a patch device for selectively destroying or inhibiting the rapid division of tumor cells in accordance with embodiment 9;
FIG. 37 is a schematic view of the structure of the therapeutic bed for selectively destroying or inhibiting the rapid division of tumor cells in the embodiment 10, wherein a magnetic ring or magnetic chain is positioned above the bed plate;
FIG. 38 is a schematic view of the structure of the therapeutic bed for selectively destroying or inhibiting the rapid division of tumor cells in the embodiment 10, wherein a magnetic ring or magnetic chain is arranged below the bed plate;
FIG. 39 is a schematic view of the structure of the therapeutic bed for selectively destroying or inhibiting the rapid division of tumor cells in the embodiment 10, wherein the magnetic rings or magnetic chains are arranged on the front, back, left and right sides of the bed plate;
FIG. 40 is a schematic view of the structure of a therapeutic bed for selectively destroying or inhibiting the rapid division of tumor cells in the embodiment 10, wherein the bed plate is positioned in a magnetic ring or a magnetic chain;
FIG. 41 is a schematic view of the structure of a therapeutic bed for selectively destroying or inhibiting the rapid division of tumor cells according to embodiment 11;
FIG. 42 is a schematic view of an alternating electric field generated within a magnetic loop or flux linkage;
FIG. 43 is a schematic representation of the growth and proliferation inhibition of human dermal fibroblasts 3T3 when a device for selectively destroying or inhibiting mitosis in tumor cells is applied to human dermal fibroblasts 3T 3;
FIG. 44 is a graph showing the inhibition rate of human dermal fibroblasts 3T3 when a device for selectively destroying or inhibiting mitosis of tumor cells is applied to human dermal fibroblasts 3T 3;
FIG. 45 is a schematic illustration of the proliferation assay of human non-small cell lung cancer cells when an apparatus for selectively destroying or inhibiting tumor cell mitosis is applied to human non-small cell lung cancer cells;
FIG. 46 is a graph showing the inhibition rate of a human non-small cell lung cancer cell when an apparatus for selectively destroying or inhibiting mitosis in a tumor cell is applied to the human non-small cell lung cancer cell;
FIG. 47 is a schematic illustration of the detection of proliferation of human glioblastoma cells when a device for selectively destroying or inhibiting mitosis in tumor cells is applied to human glioblastoma cells;
FIG. 48 is a graph showing the inhibition rate of human glioblastoma cells by an apparatus for selectively disrupting or inhibiting mitosis in tumor cells when applied to human glioblastoma cells;
FIG. 49 is a schematic representation of the proliferation assay of murine glioma cells when a device for selectively disrupting or inhibiting the mitosis of tumor cells is applied to the murine glioma cells;
FIG. 50 is a graph showing the inhibition rate of murine glioma cells when acted upon by a device for selectively disrupting or inhibiting the mitosis of tumor cells.
Detailed Description
The present invention will be described in detail with reference to the accompanying drawings.
Embodiment 1:
the present embodiment provides an alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells, as shown in fig. 1, comprising a closed magnetic ring or magnetic chain 1 and at least one metal coil 2 wound on the magnetic ring or magnetic chain 1, wherein the metal coil 2 is wound around part or all of the magnetic ring or magnetic chain 1, and a closed loop is formed between two ends of the metal coil 2 and an alternating signal generating circuit; in use of the device, a carrier 3 of rapidly dividing tumour cells is located within or to one side of the magnetic ring or flux linkage 1. The included angle between the plane of the magnetic ring or magnetic chain 1 and the carrier 3 of the rapidly dividing tumor cells is changed within the range of 0-90 degrees. If the carrier 3 of the tumor cells which are dividing rapidly is positioned at one side of the magnetic ring or the magnetic chain, an included angle of 0 degree is preferably formed between the plane where the magnetic ring or the magnetic chain 1 is positioned and the carrier 3 of the cells which are dividing; if the carrier 3 of the rapidly dividing tumor cell is located in the magnetic ring or magnetic chain 1, an angle of 90 degrees is preferably formed between the plane of the magnetic ring or magnetic chain 1 and the carrier 3 of the rapidly dividing tumor cell, or the carrier 3 of the rapidly dividing tumor cell and the magnetic ring or magnetic chain 1 are located on the same plane.
The magnetic ring or flux linkage 1 is made of a flexible soft magnetic material or a rigid soft magnetic material. The flexible soft magnetic material is any one or combination of the following materials: electromagnetic pure iron, iron-silicon alloy, iron-nickel alloy, iron-aluminum alloy, iron-silicon-aluminum alloy, iron-cobalt alloy, amorphous soft magnetic alloy and ultra-microcrystalline soft magnetic alloy; the rigid soft magnetic material is any one or combination of the following materials: pure iron and low carbon steel, iron-cobalt alloy, soft magnetic ferrite, amorphous nanocrystalline alloy.
The alternating signal generating circuit needs a power supply circuit, i.e. a switching power supply circuit, as shown in fig. 2, and converts an alternating current commercial power (e.g. 220V 50Hz of the chinese standard) or a battery power into a direct current voltage V through the switching power supply circuitDDAnd supplies power to the alternating signal generating circuit.
The alternating signal generating circuit is used for generating alternating signals meeting the requirements of frequency, amplitude and time interval. The alternating signal generating circuit can be any one or combination of a constant-amplitude sine wave generator circuit, a reducing-amplitude sine wave generator circuit, an amplifying sine wave generator circuit, a sine wave generator circuit with the amplitude increasing first and then reducing, and a sine wave circuit with the frequency continuously changing between the maximum value and the minimum value.
The constant-amplitude sine wave generator circuit is a Clara wave oscillation circuit or a Mathler oscillation circuit; or, the constant-amplitude sine wave generator circuit mainly comprises a sawtooth wave generator and a voltage-controlled oscillator; or, the constant-amplitude sine wave generator circuit mainly comprises a triangular wave generator and a voltage-controlled oscillator; the amplitude-reducing sine wave generator circuit is an LC oscillator circuit; the amplification sine wave generator circuit mainly comprises a sine wave generator, a sawtooth wave generator and an analog multiplier circuit; the first-increasing and second-decreasing sine wave generator circuit mainly comprises a high-frequency sine wave generator, a low-frequency sine wave generator and an analog multiplier circuit; or the first increasing and then decreasing sine wave generator circuit mainly comprises three circuits of a sine wave generator, a triangular wave generator and an analog multiplier circuit.
In order to realize equal time intervals or random time intervals among a plurality of groups of sine waves, a periodic signal generating circuit, a random signal generating circuit or the combination of the periodic signal generating circuit and the random signal generating circuit is also needed, an electric control switch is also connected between a VDD power supply and the power supply input end of the alternating signal generating circuit, and an output signal of the random/periodic signal generating circuit is used for controlling the electric control switch. The random/periodic signal generating circuit may control the respective alternating signal generating circuits so as to divide the generated alternating signals into a plurality of series, and the timing of occurrence of each series may be periodic, random or continuous.
Fig. 3 shows a typical amplitude-reduced sine wave generation circuit, which is an LC oscillator circuit incorporating an inductor for generating a periodic/random time interval amplitude-reduced sine wave. Wherein C in the figure and a primary coil L wound on a magnetic ring or a magnetic chain 1 form an LC oscillator circuit. Because of the non-negligible resistance in the inductor L, the LC oscillator is a ringing oscillator with an oscillation frequency of. In fig. 3, the periodic/random signal generating circuit generates a periodic signal or a random signal to control the electrically controlled switch (usually implemented by power MOS transistors, BJT transistors, IGBT transistors, relays, etc.). And the electric control switch is turned off immediately after being turned on, so that the LC oscillator is full of energy and starts to resonate. Thus, the ringing circuit is turned on at periodic/random intervals.
When the alternating signal generating circuit is a constant-amplitude sine wave generator circuit, the constant-amplitude sine wave generator circuit may be a clara wave oscillating circuit, as shown in fig. 4. The circuit incorporates a sine wave generator with an inductor coil for generating a continuous constant amplitude sine wave. The inductor L can be directly a metal coil 2 in an alternating electric field device for selectively destroying or inhibiting the mitosis of tumor cells, and the function of the invention can also be realized if a sine wave generator with other structures, such as a sine wave generator generated by an RC oscillator, is used for sending to a primary coil of a transformer.
On the basis of the circuit shown in fig. 4, an electrically controlled switch is connected to the VDD power supply and the power input terminal of the clabber oscillator circuit, and a random/periodic signal generating circuit is used to generate a periodic signal or a random signal, as shown in fig. 5. The current waveform of the output preset alternating current is a constant-amplitude sine wave at periodic time intervals or a constant-amplitude sine wave at random time intervals.
When the alternating signal generating circuit is a constant-amplitude sine wave generator circuit, the constant-amplitude sine wave generator circuit may also be a schiller oscillator circuit (see fig. 6) which is a sine wave generator combined with an inductor coil and used for generating a continuous sine wave. The inductor L can be directly a metal coil 2 in an alternating electric field device for selectively destroying or inhibiting the mitosis of tumor cells, and the function of the invention can also be realized if a sine wave generator with other structures, such as a sine wave generator generated by an RC oscillator, is used for sending to a primary coil of a transformer.
On the basis of the circuit shown in fig. 6, an electronic control switch is connected to the VDD power supply and the power supply input end of the miller oscillation circuit, and a periodic signal or a random signal is used as an auxiliary signal, so that a constant-amplitude sine wave with periodic time intervals or a constant-amplitude sine wave with random time intervals is realized as shown in fig. 7.
When the alternating electric field device for selectively destroying or inhibiting the mitosis of the tumor cells in the embodiment is used, the carrier 3 of the tumor cells which are dividing rapidly is placed in or at one side of the magnetic ring or the magnetic chain 1, alternating current with the frequency of 30 kHz-300 kHz and random amplitude is generated after the alternating signal generating circuit is electrified, when the alternating current is output to the metal coil 2, an alternating magnetic field is generated in the magnetic ring or the magnetic chain 1, the direction of the alternating magnetic field is consistent with the direction of the magnetic ring or the magnetic chain 1, and a closed loop is formed like the magnetic ring or the magnetic chain 1. The alternating magnetic field forms an alternating electric field in its vertical direction, i.e. in a direction perpendicular to the plane of the magnetic ring or flux linkage 1. As shown in fig. 42. Since tumor cells are more susceptible to destruction by alternating electric fields of a specific frequency and strength characteristic of electric fields when they are dividing rapidly. Thus, when the rapidly dividing tumor cell carrier 3 is located within the alternating electric field, the rapidly dividing tumor cell is affected by the alternating electric field. The alternating electric field of the specific frequency and electric field strength characteristic is maintained for a period of time to selectively destroy the rapidly dividing tumor cells, while normal cells are not damaged due to the insensitivity to the alternating electric field of the specific frequency and electric field strength characteristic. This selectively destroys rapidly dividing cells like tumor cells without damaging normal cells.
The preset alternating current is any current waveform with the frequency of 30 kHz-300 kHz, and the strength of the preset alternating electric field is 0.1V/cm-10V/cm.
The current waveform of the preset alternating current is a continuous sine wave with a constant amplitude, and the frequency and the amplitude of the continuous sine wave are the same, as shown in fig. 8. Both the alternating signal generating circuits shown in fig. 4 and 6 are capable of generating a continuous constant amplitude sine wave as shown in fig. 8.
The current waveform of the preset alternating current is a plurality of groups of constant-amplitude sine waves with periodic time intervals, the frequency, the amplitude and the duration of the constant-amplitude sine waves with the periodic time intervals of each group are the same, and the idle time intervals between the constant-amplitude sine waves with the periodic time intervals of two adjacent groups are the same, as shown in fig. 9. The duration of the constant-amplitude sine waves of each group of periodic time intervals is at least one sine wave period; the idle time interval between the constant-amplitude sine waves of the two adjacent groups of period time intervals is at least one sine wave period. The alternating signal generating circuits shown in fig. 5 and 7 are both capable of generating a constant amplitude sine wave with periodic time intervals as shown in fig. 9.
The current waveform of the preset alternating current is a plurality of groups of constant-amplitude sine waves with random time intervals, the frequency of the constant-amplitude sine waves with the random time intervals is the same, the amplitude of the constant-amplitude sine waves with the random time intervals is the same, the duration of the constant-amplitude sine waves with the random time intervals is random, and the idle time intervals between the constant-amplitude sine waves with the random time intervals of two adjacent groups are the same or random, as shown in fig. 10. The duration of each group of constant-amplitude sine waves at random time intervals is at least one sine wave period; the idle time interval between two adjacent groups of constant-amplitude sine waves at random time intervals is at least one sine wave period. The alternating signal generating circuits shown in fig. 5 and 7 are both capable of generating sets of randomly time spaced constant amplitude sine waves as shown in fig. 10.
The current waveform of the preset alternating current is a plurality of groups of amplitude-reducing sine waves with periodic time intervals, the frequency of the amplitude-reducing sine waves with the periodic time intervals of each group is the same, the initial amplitude is the same, the damping attenuation coefficient of the amplitude is the same, and the idle time intervals between the amplitude-reducing sine waves with the periodic time intervals of two adjacent groups are the same; as shown in fig. 11. After the amplitude-reducing sine wave of each group of periodic time intervals is attenuated to 0, starting the amplitude-reducing sine wave of the next group of periodic time intervals after a fixed idle time interval; the idle time interval between two adjacent groups of amplitude-reduced sine waves with the period time interval is at least one sine wave period; the attenuation coefficient of the damped sine waves of each group of periodic time intervals is R/2L, wherein R is the series resistance value or the equivalent series parasitic resistance value of the LC oscillating circuit, L is the inductance of the LC oscillating circuit, and C is a capacitance value connected in parallel to the inductance L; the duration of the damped sinusoids of each group of periodic time intervals is 5-30 sinusoid periods. By changing the resistance value R, the attenuation coefficient can be changed. The decay system is usually evaluated simply by how many sustained sinusoids per group. The sine wave attenuation coefficient (equivalent to the series resistance value R of the regulating inductor L) can be preset according to the position of a patient and the severity of the disease. An alternating signal generating circuit as shown in fig. 12 (one of the alternating signal generating circuits of fig. 1, which generates a reduced sine wave signal at fixed time intervals or at random time intervals), i.e., a reduced sine wave signal capable of generating a plurality of sets of periodic time intervals as shown in fig. 11. The inductor L in fig. 12 may be directly replaced by a primary winding of a transformer, which is shown in fig. 3.
The current waveform of the preset alternating current is a plurality of groups of amplitude-reduced sine waves with random time intervals, the frequency of the amplitude-reduced sine waves with random time intervals in each group is the same, the starting amplitudes are the same or different, the attenuation coefficients are the same or different, and the idle time intervals between two adjacent groups of the amplitude-reduced sine waves with random time intervals are random, as shown in fig. 13. The attenuation coefficient of each group of the damped sine waves at random time intervals is R/2L, wherein R is the series resistance value or the equivalent series parasitic resistance value of the LC oscillating circuit, L is the inductance of the LC oscillating circuit, and C is a capacitance value connected in parallel to the inductance L; the duration of each group of the amplitude-reduced sine waves at random time intervals is 5-30 sine wave periods. By changing the resistance value R, the attenuation coefficient can be changed. The decay system is usually evaluated simply by how many sustained sinusoids per group. The sine wave attenuation coefficient (which is equivalent to the series resistance value R of the regulating inductor L) can be set according to the position of a patient and the severity of the disease. An alternating signal generating circuit as shown in figure 12 is capable of generating a plurality of sets of randomly time spaced reduced sine waves as shown in figure 13.
The current waveform of the preset alternating current is a plurality of groups of amplified sine waves with periods or random time intervals or continuous amplitudes gradually increased, the frequency of each group of amplified sine waves is the same, the amplitudes are gradually increased, and the idle time intervals between two adjacent groups of amplified sine waves are the same or random. The duration of each group of amplified sine waves is 5-30 sine wave periods. The circuit shown in fig. 15 is one of the circuits that generates the waveforms shown in fig. 14: comprises a high-frequency sine wave generator, a sawtooth wave generator and an analog multiplier circuit, wherein the analog multiplier circuit is connected with an induction coil, and the induction coil can directly adopt a metal coil 2 in an alternating electric field device for selectively destroying or inhibiting the mitosis of tumor cells. The high-frequency sine wave generated by the high-frequency sine wave generator is multiplied by the sawtooth wave generated by the sawtooth wave generator, so that a plurality of groups of amplified sine waves with gradually increased amplitude values are obtained. The waveform generation principle is shown in fig. 16: and multiplying the second waveform and the third waveform to obtain the first waveform.
The current waveform of the preset alternating current is a plurality of groups of periodic or random time intervals or continuous amplitude values, wherein the amplitude values of each group are increased firstly and then decreased by sine waves, the frequency of each group of amplitude values is the same, the amplitude values are gradually increased firstly and then gradually decreased, and the idle time intervals between the groups of amplitude values, which are increased firstly and then decreased by sine waves, are the same or random. The circuit shown in fig. 18 is a circuit for generating a sine wave waveform with an amplitude increasing and then decreasing, and comprises a high-frequency sine wave generator, a low-frequency sine wave generator and an analog multiplier circuit, wherein the analog multiplier circuit is connected with an induction coil, and the induction coil can directly adopt a metal coil 2 in an alternating electric field device for selectively destroying or inhibiting the mitosis of tumor cells. The high frequency sine wave generated by the high frequency sine wave generator is multiplied by the low frequency sine wave generated by the low frequency sine wave generator to obtain a plurality of groups of sine waves with increasing amplitude and then decreasing amplitude as shown in fig. 17, and the waveform generation principle is shown in fig. 19: the second and third waveforms are multiplied to obtain the first waveform.
The circuit shown in fig. 20, which is another circuit for generating a plurality of sets of waveforms of increasing and decreasing amplitudes of random time intervals shown in fig. 17, comprises a high-frequency sine wave generator, a triangle wave generator and an analog multiplier circuit, wherein the analog multiplier circuit is connected with an inductance coil, and the inductance coil can be directly used as a metal coil 2 in an alternating electric field device for selectively destroying or inhibiting the mitosis of tumor cells. The high frequency sine wave generated by the high frequency sine wave generator and the triangular wave generated by the triangular wave generator are multiplied to obtain the sine wave with the amplitude increased and then decreased as shown in fig. 17. The waveform generation principle is shown in fig. 21: the second and third waveforms are multiplied to obtain the first waveform. The circuit for generating the sine wave waveform of fig. 17 in which the amplitude is increased and then decreased is not limited to the circuits shown in fig. 18 and 20.
The current waveform of the preset alternating current is similar to a frequency modulated continuous FMCW wave, and the frequency of the frequency modulated continuous FMCW wave increases linearly within a preset time, as shown in the first waveform of fig. 22. The second waveform corresponds to the sine wave frequency of the first waveform. The starting frequency and the final frequency are both within a preset range of 30 KHz-300 KHz, the limit value of the highest frequency is 300kHz, and the limit value of the lowest frequency is 30 kHz. In a certain device, the highest frequency and the lowest frequency are selected and set according to specific cancer cell attributes, but always fall within the range of 30 KHz-300 KHz. A preset time interval is arranged between the highest frequency and the lowest frequency; the duration of the linear increase from the lowest frequency to the highest frequency is 5-100 sine wave periods.
Fig. 23 is a circuit diagram of one of the circuits for generating the waveform of fig. 22, which includes a sawtooth generator and a voltage controlled oscillator, the voltage controlled oscillator is connected with an inductance coil, and the inductance coil can be directly used as the metal coil 2 in the magnetic ring array device for treatment. The sawtooth wave voltage generated by the sawtooth wave generator is used for controlling the voltage-controlled oscillator, and the sine wave with continuously variable frequency is output, namely the frequency modulation continuous wave FMCW.
The current waveform of the preset alternating current is similar to a frequency modulated continuous FMCW wave, and the frequency of the frequency modulated continuous FMCW wave is linearly increased and then linearly decreased within a preset time, as shown in the first waveform of fig. 24. The second waveform corresponds to the sine wave frequency of the first waveform. The starting frequency and the final frequency are both within a preset range of 30 KHz-300 KHz, the limit value of the highest frequency is 300kHz, and the limit value of the lowest frequency is 30 kHz. In a certain device, the highest frequency and the lowest frequency are selected and set according to specific cancer cell attributes, but always fall within the range of 30 KHz-300 KHz. A preset time interval is arranged between the highest frequency and the lowest frequency; the duration of linearly increasing from the lowest frequency to the highest frequency is 5-100 sine wave periods; the duration of the linear reduction from the highest frequency to the lowest frequency is 5-100 sine wave periods.
Fig. 25 is a circuit diagram of one of the circuits for generating the waveform of fig. 24, which includes a triangle wave generator and a voltage controlled oscillator, the voltage controlled oscillator is connected with an inductance coil, and the inductance coil can be directly used as the metal coil 2 in the magnetic ring array device for treatment. The triangular wave voltage generated by the triangular wave generator is used for controlling the voltage-controlled oscillator, and a sine wave with continuously variable frequency is output, namely the continuous FMCW wave is modulated by the frequency.
The current waveform of the preset alternating current is similar to a frequency modulated continuous FMCW wave, and the frequency of the frequency modulated continuous FMCW wave is increased and then decreased within a preset time, as shown in the first waveform of fig. 26. The second waveform corresponds to the sine wave frequency of the first waveform. The increasing and decreasing frequency changes follow a sine wave law. The starting frequency and the final frequency are both within a preset range of 30 KHz-300 KHz, the limit value of the highest frequency is 300kHz, and the limit value of the lowest frequency is 30 kHz. In a certain device, the highest frequency and the lowest frequency are selected and set according to specific cancer cell attributes, but always fall within the range of 30 KHz-300 KHz. A preset time interval is arranged between the highest frequency and the lowest frequency; the duration from the lowest frequency to the highest frequency is 5-100 sine wave periods; the duration of the reduction from the highest frequency to the lowest frequency is 5-100 sine wave cycles.
Fig. 27 is a circuit diagram of one of the waveforms of fig. 26, which includes a sine wave generator and a voltage controlled oscillator connected to an inductor coil that can be directly used as the metal coil 2 in the magnetic ring array device for treatment. The sine wave voltage generated by the sine wave generator is used for controlling the voltage-controlled oscillator, and the sine wave with continuously variable frequency is output, namely the frequency modulation continuous wave FMCW.
In the embodiment, an alternating electric field with the frequency of 30 kHz-300 kHz and the alternating electric field with the intensity of 0.1V/cm-10V/cm is applied to normal cells and different tumor cell lines, so that the device in the embodiment can selectively kill tumor cells and inhibit the growth of the tumor cells by adding the field intensity with the specific frequency (between 30kHz and 300 kHz) and the intensity (between 0.1V/cm and 10V/cm). The experimental method is as follows:
normal cells, human skin fibroblast 3T3, three cancer cells, human lung adenocarcinoma cell a549, human glioblastoma cell U87 and murine glioma cell C6 were inoculated in 96-well plates, respectively. The experimental group places the cells in magnetic rings generating electric fields with different electric field strengths and different frequencies, places the magnetic rings and the cells in a carbon dioxide incubator with the volume of 54 multiplied by 50 multiplied by 68cm, the incubator is grounded, the internal electric field strength is 0, and no influence of an external electric field exists; the control group was cultured in the same incubator routinely without electric field. The cells of the experimental group and the cells of the control group are inoculated in the same quantity and the same density, the culture conditions are DEME +10% FBS culture medium, the cells are cultured for 1 to 14 days, the CCK8 cell proliferation experiment detection is carried out, and the cell proliferation inhibition rate is calculated.
The experimental results are as follows:
when the electric field intensity range is 0.1V/cm-10V/cm and the frequency is 30 kHz-300 kHz, the inhibition results on the proliferation of normal cells and three different tumor cells are as follows:
1, effect on normal cells:
in the present embodiment, human skin fibroblasts 3T3 were cultured in the alternating electric field environment (test group/experimental group) and in the normal culture environment (control group/control group), respectively, and the proliferation and inhibition of the alternating electric field on the growth of human skin fibroblasts 3T3 were examined, with the results expected: the alternating electric field has no obvious influence on the growth and proliferation of human skin fibroblast 3T3, and the cell proliferation of the experimental group is consistent with that of the control group, as shown in figure 43. The inhibition rate of the alternating electric field on the growth of the human skin fibroblast 3T3 is close to 0, and the proliferation inhibition effect is not obvious, as shown in figure 44.
2, cell proliferation inhibition by applying electric field to human lung adenocarcinoma cells
As shown in fig. 45 and 46, when the inhibition effect is the best for the human lung adenocarcinoma cells a549, the inhibition rate is about 40%, i.e., the number of the inhibited cells accounts for 40% of the total number of the cells in the control group.
3, cell proliferation inhibition by applying electric field to human glioblastoma cells
As shown in fig. 47 and 48, the inhibition rate of U87 was about 35% when the inhibition effect was the best, i.e., the number of cells inhibited was 35% of the total number of cells in the control group.
Inhibition of cell proliferation by applying electric field to rat glioma cells
As shown in fig. 49 and 50, for murine glioma cell C6, the inhibition rate was 0.45 when the inhibition effect was the best, i.e., the number of cells inhibited was 45% of the total number of cells in the control group.
Embodiment 2:
according to the device of embodiment 1, this embodiment provides a bracelet, an ankle ring, a neck ring, a waistband, a hip bag or a belly band for selectively destroying or inhibiting tumor cell division, as shown in fig. 28, the bracelet, the ankle ring, the neck ring or the waistband includes a wearing component 4 and the alternating electric field device of embodiment 1 for selectively destroying or inhibiting tumor cell division, the wearing component 4 is an endless or closed loop structure made of ABS, HDPE, PC, FRP, fiber, nylon, rubber or silica gel material, a magnetic ring or a magnetic chain is installed on the outer sidewall of the wearing component 4, a slot 401 is opened on the sidewall of the wearing component 1, and the magnetic ring or the magnetic chain 1 is clamped in the slot 401 to realize the installation connection with the wearing component 1; a closed loop is formed between the two ends of the metal coil 2 and the alternating signal generating circuit.
When using the bracelet, the foot ring, the neck ring or the waist belt, if the wearing component is a closed ring structure, as shown in fig. 28, the bracelet, the foot ring, the neck ring or the waist belt can be directly sleeved on the arm, the ankle, the neck or the waist of the patient through the wearing component 4. If the wearing component 4 is an annular structure with non-closed ends, as shown in fig. 29, the wearing component covers the bracelet, the foot ring, the neck ring or the waist belt on the arm, the ankle, the neck or the waist of the patient, and then the two ends of the wearing component 4 are connected through the buckle 402.
When tumor cells exist in the arms, legs, necks, waists, abdomens or pelvic cavities of a patient, the patient only needs to wear the bracelet, the ankles, the neckloop, the waistbands, the buttocks bag or the abdominal belt, and then selects the current waveform of the preset alternating current with proper frequency and amplitude through the alternating signal generating circuit according to the specific situation of the tumor.
Otherwise, this embodiment is identical to embodiment 1, and will not be described herein.
Embodiment 3:
this embodiment is substantially the same as embodiment 2, and differs only in the connection form between the magnet ring or the magnet chain 1 and the wearing unit 4 in this embodiment. In this embodiment, the side wall of the wearing component 4 is provided with a binding mechanism 403, and the wearing component 4 and the magnetic ring or the magnetic linkage 1 are bound together through the binding mechanism 403. The binding mechanism 403 is a plurality of pairs of straps circumferentially disposed on the sidewall of the wearing component, one end of each of the plurality of pairs of straps is fixed on the sidewall of the wearing component 4, and the other end is tied to the magnetic ring or the magnetic chain 1. As shown in fig. 30.
Otherwise, this embodiment is identical to embodiment 2, and will not be described herein.
Embodiment 4:
this embodiment is substantially the same as embodiment 3, except that the binding means 403 of the wearing unit 4 in this embodiment is a plurality of pairs of hidden button sets circumferentially provided on the side wall of the wearing unit, the plurality of pairs of hidden button sets are fixed to the side wall of the wearing unit through respective connectors, and the wearing unit 4 can be attached to a magnetic ring or a magnetic chain through each pair of hidden button sets. As in fig. 31.
Otherwise, this embodiment is completely the same as embodiment 3, and will not be described herein.
Embodiment 5:
this embodiment is substantially the same as embodiment 2, and differs only in the connection form between the magnet ring or the magnet chain 1 and the wearing unit 4 in this embodiment. In this embodiment, the wearing component 4 may be a shell made of fiber, nylon, rubber or silica gel material directly wrapped outside the magnetic ring or the magnetic chain 1. As in fig. 32.
Otherwise, this embodiment is identical to embodiment 2, and will not be described herein.
Embodiment 6:
according to the device of embodiment 1, this embodiment provides a vest for selectively destroying or inhibiting tumor cell division, as shown in fig. 33, the vest comprises a wearing member 4 and the alternating electric field device of embodiment 1 for selectively destroying or inhibiting tumor cell division, the wearing member 4 is made of ABS, HDPE, PC, FRP, fiber, nylon, rubber or silicone material and is made into a vest shape, a magnetic ring or magnetic chain 1 is sewn on the outer side wall of the wearing member 4, or the connection relationship between the magnetic ring or magnetic chain 1 and the wearing member 4 can be the same as any one of embodiments 2 to 5; a closed loop is formed between the two ends of the metal coil 2 and the alternating signal generating circuit.
The vest is used when tumors exist in the chest, abdomen or back of a patient, and can be used for treating lung cancer, esophageal cancer, mediastinal tumor, liver cancer, stomach cancer, pancreatic cancer, kidney cancer and the like. The patient only needs to wear the vest and then selects the current waveform of the preset alternating current with proper frequency and amplitude through the alternating signal generating circuit according to the specific condition of the tumor.
Otherwise, this embodiment is identical to embodiment 1, and will not be described herein.
Embodiment 7:
according to the apparatus of embodiment 1, this embodiment provides a wearable device for selectively destroying or inhibiting tumor cells from rapidly dividing, as shown in fig. 34, the wearable device may be in the shape of a bra, the wearable device includes a bra-shaped wearable component 4 and the alternating electric field apparatus of embodiment 1 disposed at the positions of nipples on both sides of the bra for selectively destroying or inhibiting tumor cells from mitosis, the wearable component 4 is made of fiber, nylon, rubber or silicone material and is in the shape of a bra, the magnetic ring or chain 1 is sewn on the outer side wall of the wearable component 4, or the connection relationship between the magnetic ring or chain 1 and the wearable component 4 may be the same as any one of embodiments 2 to 5; a closed loop is formed between the two ends of the metal coil 2 and the alternating signal generating circuit.
When a tumor such as breast cancer exists in the chest of a patient, the bra is worn by the patient, and then the current waveform of the preset alternating current with proper frequency and amplitude is selected through the alternating signal generating circuit according to the specific condition of the tumor.
Otherwise, this embodiment is identical to embodiment 1, and will not be described herein.
Embodiment 8:
according to the device of embodiment 1, this embodiment provides a hat or helmet for selectively destroying or inhibiting tumor cells from dividing rapidly, as shown in fig. 35, the hat comprises a wearing component 4 and the alternating electric field device of embodiment 1 for selectively destroying or inhibiting tumor cells from dividing mitotically, the wearing component 4 is made of ABS, HDPE, PC, FRP, fiber, nylon, rubber or silica gel material into hat or helmet shape, a magnetic ring or magnetic chain 1 is sewn on the outer sidewall of the wearing component 4, or the connection relationship between the magnetic ring or magnetic chain 1 and the wearing component 4 can be the same as any one of embodiments 2 to 5; a closed loop is formed between the two ends of the metal coil 2 and the alternating signal generating circuit.
When tumor cells such as glioma exist on the head of a patient, the cap or helmet is used, the patient only needs to wear the cap or helmet, and then the alternating signal generating circuit selects the current waveform of the preset alternating current with proper frequency and amplitude according to the specific situation of the tumor. Otherwise, this embodiment is identical to embodiment 1, and will not be described herein.
Embodiment 9:
the alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells in the present embodiment is made to be smaller in size for treating tumor cells in local parts of a patient, and the small-sized device can be fixed on clothes or other wearing equipment or pasted on the surface of a wounded part of a body, as shown in fig. 36, for treating tumor at the position of the chest of the patient, and the plane of the magnetic ring or magnetic chain 1 in the device is in a basically parallel fit state with the chest, so that magnetic induction lines in the magnetic ring or magnetic chain 1 can enter the skin of the wounded part to achieve the purpose of damaging the tumor cells of the wounded part. Due to the small size, the action area of the generated electric field is small, the path directivity number is small, and the treatment can be carried out aiming at the lesion with the determined position on the body surface and the body.
Otherwise, this embodiment is identical to embodiment 1, and will not be described herein.
Embodiment 10:
according to the device in embodiment 1, the present embodiment provides a therapeutic bed for selectively destroying or inhibiting tumor cells from rapidly dividing, the therapeutic bed comprises a bed plate 5, a positioning assembly and the device for selectively destroying or inhibiting dividing cells in embodiment 1, wherein a magnetic ring or magnetic chain 1 is mounted on a positioning frame 6 in the positioning assembly, a closed loop is formed between two ends of a metal coil 2 and an alternating signal generating circuit, the magnetic ring or magnetic chain 1 is located above (as shown in fig. 37) or below (as shown in fig. 38) the bed plate 5, and a plane of the magnetic ring or magnetic chain 1 and a plane of the bed plate 5 are parallel to each other. Or the magnetic ring or the magnetic chain 1 is positioned at any side of the periphery of the bed plate 5, and the plane where the magnetic ring or the magnetic chain 1 is positioned is perpendicular to the plane where the bed plate 5 is positioned (as shown in fig. 39, including the situation that the magnetic ring or the magnetic chain 1 is positioned at the front, the back, the left and the right sides of the bed plate 5). Or, the bed plate 5 is located in the magnetic ring or the magnetic chain 1, and the plane of the magnetic ring or the magnetic chain 1 is perpendicular to the plane of the bed plate 5, as shown in fig. 40.
When the treatment bed is used, a patient directly lies on the bed plate 5, and then the current waveform of the preset alternating current with proper frequency and amplitude is selected through the alternating signal generating circuit according to the specific condition of the tumor. The treatment bed can be suitable for treating various tumors.
Otherwise, this embodiment is identical to embodiment 1, and will not be described herein.
Embodiment 11:
the present embodiment is a further improvement of embodiment 9, and the main improvement is that, in the present embodiment, in order to adjust an included angle between a plane where a bed plate 5 and a magnetic ring or a magnetic chain 1 in a treatment bed are located, to adjust an included angle between a magnetic induction line in the magnetic ring or the magnetic chain 1 and the bed plate 5, and to adjust an included angle between the magnetic induction line and tumor cells in a patient body in a multi-direction, so as to achieve the purpose of optimizing a treatment effect, the positioning assembly in the present embodiment further includes an angle adjusting mechanism, the angle adjusting mechanism includes a driving cylinder 7 and a rocker arm 8, the driving cylinder 7 is fixed on the positioning frame 6, one end of the rocker arm 8 is connected with a telescopic rod of the driving cylinder 7, the other end of the rocker arm is connected with the magnetic ring or the magnetic chain 1 through a universal shaft 9, and the magnetic ring or the magnetic chain 1 is rotatably connected on the positioning frame 6 through a rotating shaft. As in fig. 41. When the adjustment is needed, the rocker arm 8 drives the magnetic ring or the magnetic chain 1 to rotate around the rotating shaft by driving the stretching of the cylinder 7, so that the included angle between the bed plate 5 and the plane where the magnetic ring or the magnetic chain is located can be adjusted, and finally the effect of adjusting the included angle between the bed plate 5 and the magnetic induction lines in the magnetic ring or the magnetic chain 1 is achieved.
Otherwise, this embodiment is completely the same as embodiment 9, and will not be described herein.
It will be appreciated that the alternating electric field apparatus of the present invention for selectively disrupting or inhibiting mitosis of tumor cells may also be used for other purposes than treating tumors in a living body. In fact, selective disruption using the present device may be used in conjunction with any proliferation dividing and propagating organism, for example, tissue cultures, microorganisms such as bacteria, mycoplasma, protozoa, etc., fungi, algae, plant cells, etc.
Tumor cells as presented herein include leukemia, lymphoma, myeloma, plasmacytoma; and solid tumors. Examples of solid tumors that may be treated according to the present invention include sarcomas and carcinomas such as, but not limited to: fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, dorsal-locked epithelioma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendothelioma, synovioma, mesothelioma, leiomyosarcoma, rhabdomyosarcoma, colon cancer, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchial carcinoma, renal cell carcinoma, liver cancer, bile duct carcinoma, choriocarcinoma, seminoma, embryonic carcinoma, cervical cancer, testicular tumor, lung cancer, small-cell lung cancer, bladder cancer, epithelial cancer, glioma, astrocytic carcinoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligoglioma, meningioma, melanoma, neuroblastoma, melanoma, neuroblastoma, melanoma, neuroblastoma, melanoma, neuroblastoma, melanoma, neuroblastoma, melanoma, carcinoma of the patient's nerve, or other cell of the patient's nerve, or of the patient's skin, or the patient's skin, Neuroblastoma and retinoblastoma.
The above embodiments are merely illustrative of the technical concepts and features of the present invention, and the purpose of the embodiments is to enable those skilled in the art to understand the contents of the present invention and implement the present invention, and not to limit the protection scope of the present invention. All equivalent changes and modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (10)
1. An alternating electric field device for selectively destroying or inhibiting tumor cell mitosis, characterized by comprising a closed magnetic ring or magnetic chain (1) and at least one metal coil (2) wound on the magnetic ring or magnetic chain (1), wherein a closed loop is formed between two ends of the metal coil (2) and an alternating signal generating circuit; in use of the device, a carrier (3) of rapidly dividing tumour cells is located within or to one side of the magnetic ring or flux linkage;
the alternating signal generating circuit is any one or combination of the following: the sine wave generator comprises a constant-amplitude sine wave generator circuit, a reducing sine wave generator circuit, an amplifying sine wave generator circuit, a sine wave generator circuit with amplitude increasing and then reducing, and a sine wave circuit with frequency continuously changing between a maximum value and a minimum value; wherein, the inductance in each sine wave generator circuit is the metal coil (2);
the alternating signal generating circuit loads a certain constant frequency with a current waveform of 30 kHz-300 kHz or a preset alternating current with continuously changed frequency on the metal coil (2), the preset alternating current can enable a preset alternating magnetic field to be generated in the magnetic ring or the magnetic chain (1), and the preset alternating magnetic field can form a preset alternating electric field which can destroy or inhibit the rapidly dividing tumor cells in the carrier in the direction perpendicular to the magnetic ring or the magnetic chain (1) and has the strength of 0.1V/cm-10V/cm and does not act on normal cells.
2. A magnetic ring array therapy device as claimed in claim 1, further comprising a random/periodic signal generation circuit, an electrically controlled switch connected between the VDD supply and the power input of the alternating signal generation circuit, the output signal of the random/periodic signal generation circuit being used to control the electrically controlled switch.
3. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in tumor cells according to claim 2 wherein the constant amplitude sine wave generator circuit is a Clara wave oscillator circuit or a Mathler oscillator circuit, and the preset alternating current is output in a waveform of continuous constant amplitude sine waves, sets of periodic time interval constant amplitude sine waves or sets of random time interval constant amplitude sine waves.
4. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in a tumor cell according to claim 2 wherein the constant amplitude sine wave generator circuit consists essentially of a sawtooth generator and a voltage controlled oscillator connected to an inductive coil;
the sawtooth wave voltage generated by the sawtooth wave generator controls the voltage-controlled oscillator, and the output current waveform of the preset alternating current is similar to a frequency modulation continuous FMCW wave, multiple groups of FMCW waves with periodic time intervals or multiple groups of FMCW waves with random time intervals.
5. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in a tumor cell according to claim 2 wherein the constant amplitude sine wave generator circuit consists essentially of a triangle wave generator and a voltage controlled oscillator connected to an inductor;
the triangular wave voltage generated by the triangular wave generator controls the voltage-controlled oscillator, and the output current waveform of the preset alternating current is similar to a frequency modulation continuous FMCW wave, multiple groups of FMCW waves with periodic time intervals or multiple groups of FMCW waves with random time intervals.
6. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in a tumor cell according to claim 2 wherein the constant amplitude sine wave generator circuit consists essentially of a sine wave generator and a voltage controlled oscillator connected to an inductor;
the sine wave voltage generated by the sine wave generator controls the voltage-controlled oscillator, and the current waveform of the output preset alternating current is similar to a frequency modulation continuous FMCW wave, multiple groups of FMCW waves with periodic time intervals or multiple groups of FMCW waves with random time intervals.
7. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in tumor cells according to claim 2 wherein the dampened sine wave generator circuit is an LC oscillator circuit, the current waveform of the preset alternating current output being a continuous dampened sine wave, a plurality of sets of periodic time spaced dampened sine waves, or a plurality of sets of random time spaced dampened sine waves.
8. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in tumor cells according to claim 2 wherein the amplified sine wave generator circuit consists essentially of a high frequency sine wave generator, a sawtooth generator, and an analog multiplier circuit, the analog multiplier circuit connected to an inductive coil;
and multiplying the high-frequency sine wave generated by the high-frequency sine wave circuit by the sawtooth wave generated by the sawtooth wave generator, wherein the output current waveform of the preset alternating current is a continuous amplification sine wave, multiple groups of amplification sine waves with periodic time intervals or multiple groups of amplification sine waves with random time intervals.
9. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in a tumor cell according to claim 2 wherein the increase-then-decrease sine wave generator circuit consists essentially of a high frequency sine wave generator, a low frequency sine wave generator, and an analog multiplier circuit, the analog multiplier circuit connected to an inductive coil;
and multiplying the high-frequency sine wave generated by the high-frequency sine wave generator by the low-frequency sine wave generated by the low-frequency sine wave generator, wherein the output current waveform of the preset alternating current is that the amplitude is increased and then reduced by a continuous sine wave, the amplitudes of a plurality of groups of periodic time intervals are increased and then reduced by a sine wave or the amplitudes of a plurality of groups of random time intervals are increased and then reduced by a sine wave.
10. The alternating electric field apparatus for selectively disrupting or inhibiting mitosis in a tumor cell according to claim 2 wherein the up-then-down sine wave generator circuit consists essentially of a high frequency sine wave generator, a triangle wave generator, and an analog multiplier circuit, the analog multiplier circuit connected to an inductive coil;
and multiplying the high-frequency sine wave generated by the high-frequency sine wave generator by the triangular wave generated by the triangular wave generator, wherein the output current waveform of the preset alternating current is a sine wave with amplitude increased and then reduced continuously, a sine wave with amplitude increased and then reduced at a plurality of groups of periodic time intervals or a randomly amplified sine wave with a plurality of groups of random time intervals.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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CN202110843593.8A CN113577562A (en) | 2021-07-26 | 2021-07-26 | Alternating electric field device for selectively destroying or inhibiting mitosis of tumor cells |
PCT/CN2022/106357 WO2023005720A1 (en) | 2021-07-26 | 2022-07-19 | Alternating electric field apparatus for selectively destroying or inhibiting mitosis of tumor cells |
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WO2023005721A1 (en) * | 2021-07-26 | 2023-02-02 | 昆仑智鼎(北京)医疗技术有限公司 | Apparatus for selectively disrupting or inhibiting mitosis of tumor cell |
WO2023005720A1 (en) * | 2021-07-26 | 2023-02-02 | 昆仑智鼎(北京)医疗技术有限公司 | Alternating electric field apparatus for selectively destroying or inhibiting mitosis of tumor cells |
CN117398613A (en) * | 2023-11-30 | 2024-01-16 | 昆仑智鼎(北京)医疗技术有限公司 | Multidimensional electric field generating device for tumor cell mitosis and application method thereof |
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