WO2020021320A1

WO2020021320A1 - System and inductor for producing effects on a tumor by exposing to magnetic field

Info

Publication number: WO2020021320A1
Application number: PCT/IB2018/056103
Authority: WO
Inventors: Sergey PLETNEV; Andrei PLETNEV; Siarhei PANAMAROU; Mikita ZHYLINSKI; Sergey VINOGRADOV
Original assignee: Pletnev Sergey
Priority date: 2018-07-25
Filing date: 2018-08-14
Publication date: 2020-01-30
Also published as: EA201891554A1

Abstract

This invention relates to instrumentation for treatment and prevention of neoplasms in a human body such as a tumor. The system comprises an inductor section equipped with a plurality of electromagnetic coils disposed on a surface of a part of a human body and surrounding a tumor area, and connected to a current generation means for exciting magnetic fields in coils inducing therapeutic magnetic field in the tumor area. The system and inductor are characterized in that on the outside coils are interconnected with magnetic conductors, and a generator is made in the form of a pulse generator having a pulse repetition frequency of 2.5÷1,000 Hz and pulse frequency of 0.2÷500 kHz exciting the magnetic field with induction of 0.1 ÷ 100 mT. An inductor embodiment comprises two orthogonal pairs of opposite coils enclosing a part of the body in which the tumor is located, with the coils being coupled in series and connected by a common magnetically conductive layer. These system and inductor have advanced capabilities of producing effects on tumor growth in the process of conducting long-duration procedures with a high degree of comfort.

Description

SYSTEM AND INDUCTOR FOR PRODUCING EFFECTS ON A

TUMOR BY EXPOSING TO MAGNETIC FIELD

[001 ]. This invention relates to instrumentation for treatment and prevention of neoplasms in a human body such as a tumor. In this case, non-invasive techniques are advantageous.

PRIOR ART

[002] The brain cancer treatment poses a special problem. Medication-based tumor treatment is extremely complicated due to the blood-brain barrier being insurmountable for a large number of drugs.

[003]. The use of electric fields, the so-called tumor treating fields (TTF), is known for producing non-invasive exposure on a tumor [WO20171751 16 REDUCING MOTILITY OF CANCER CELLS USING TUMOR TREATING FIELDS (TTF)]. The submitted application discloses the use of effect of exposure to alternating electric fields produced by twinned capacity electrodes disposed on a patient’s head. Oscillating electric fields prevent the development of myotic division of cells of a glioblastoma in the brain tumor at frequencies of 100-300 kHz and a magnitude of 1 -3 V/ cm.

[004] One of the critical problems of this technique is the difficulty of targeting disease-affected tissues with required electric fields. Different parts of the brain are characterized by different conductivity and, hence, affected parts may be shunted.

[005]. In addition, electrodes and currents needed for treatment may cause some discomfort for the patient. The use of such technique for treatment requires that the patient’s head hair should be shaved and electrodes should be attached directly to the skin. High-frequency currents which are required to pass through a scalp and a skull to the main brain tissue frequently result in occurrence of irritation and rash.

[006]. One more problem resides in the fact that due to low allowable values of the fields’ parameters the treatment requires lengthy procedures (up to 12- hour duration), while power consumption is rather high. Taken together, this requires the use of a mobile system and rather powerful batteries. Four batteries with an operational life of 2-3 hours are used in the actual structure of the“Optune” instrument and, given the duration of one procedure being as long as 12 hours, they need to be replaced or recharged during the course of treatment. For this purpose, a patient should wear a special rucksack.

[https://www.optune.com/therapy/explore-therapyl.

[007] A technical solution which also uses TTF is more advanced, however, in this case, fields are produced by induction using an alternating electromagnetic field [Patent Application US20170014637A1 published 19.01.2017] As disclosed in the application, the system comprises a plurality of coils and an electromagnetic field generator which excites a plurality of coils to produce the tumor treatment field (TTF) in the specimen area, with the TTF having a time-dependent magnetic field component which, in its turn, induces an electric field with a magnitude of, at least, 0.1 V/ cm at a frequency from 50 kFIz to 500 kFIz. In this case, the coils are attached to a rigid shell in the form of a helmet for brain tumor treatment. In addition, the generator with coils may induce the electric field with a magnitude of 0.5, 1.0, 2, 5, 10 or 100 V/ cm.

[008]. The magnetic field has a higher penetration power and is less dependent on different conductivities of different tissue parts in the tumor area; different coil forms and configurations are provided, however, rather high power is still required to achieve the preset parameters.

[009]. The use of the magnetic field for therapy purposes is more comfortable and requires no head shaving, causes no irritation, however, the power consumption and the instrument weight respectively are still high and even may be higher as compared to the devices used in the electrode method.

[010]. In addition, both methods and devices based on them use rather high frequencies which are beyond the range of biologically perceivable frequencies, and which may cause a substantial electromagnetic heating of both inductors and entire surface and underline tissues manipulated by the system. Therefore, the inventors failed to use the method of comparison with “placebo” in the process of studying those systems, since a patient may immediately determine based on the sensation of warmth whether the device is ON or OFF.

[01 1 ]. This limitation of the frequency range precludes the use of other possibilities of exposure on tumor cells.

[012] Flowever, a method and a system of treating and suppressing tumor growth are known [Eurasian Application No. 201200044 published 30.05.2013] subject to which the main low-frequency pulsed magnetic-field exposure aimed to suppress the tumor growth is achieved by magnetic pulses with an amplitude ranging from 10 to 100 mT and a pulse frequency repetition - from 2 to 100 Hz during a series of 3-10 sessions, each with a duration of 10- 20 minutes.

[013]. Experiments to study the effects of low-frequency pulsed magnetic field have been conducted using inductors of various configurations, dimensions and capacity. During the experiments, the electric field intensity induced in tissues reached 10³ V/m. Such field values are below the sensitivity threshold and cause no discomfort for the patients.

[014] However, the abovementioned technical solution uses only the TTF low-frequency range and also requires rather high power consumption.

OBJECT OF THE PRESENT INVENTION

[015]. The object of the present invention is to enhance efficiency and extend the range of magnetic field parameters for effective tumor treatment, reduction in energy consumption, achievement of the required procedure duration and improvement of comfort during lengthy procedures.

SUMMARY OF THE PRESENT INVENTION

[016]. To achieve the object set of the present invention, a system for producing effects on a tumor from magnetic exposure comprises an inductor section equipped with a plurality of electromagnetic coils (1 ) configured to be disposed on a part of a human body and to enclose a tumor area. These coils are connected to a current generation means (2) to excite magnetic fields in coils inducing a therapeutic magnetic field for the tumor area treatment.

[017] The system according to the present invention is characterized in that coils on the outside are connected by magnetic conductors (3), and a generator is made in the form of a pulse generator having a pulse repetition frequency of 2.5÷1 ,000 Hz and a pulse frequency of 0.2÷500 kHz. In this case, the magnetic field is excited with induction of 0.1 ÷100 mT in coils.

[018]. According to further improvement, the system is characterized in that the magnetic conductors are made in the form of a magnetically conductive layer.

[019]. The magnetically conductive layer may be made of a ferromagnetic composite.

[020]. In one of the effective embodiments of the present invention, magnetic conductors are made of an amorphous metallic glass film.

[021 ] Such a solution allows both substantial reduction in energy consumption and increase in magnetic induction. A similar approach was used in the decision with respect to the EA Patent 029012 on “A Distributed Magnetic Therapeutic Inductor”. Subject to the disclosure thereof, it became possible to increase effectiveness of the magnetic field exposure on tumors during long-lasting procedures or a continuous use and improve the comfort of the therapy delivery. In addition, this provides new opportunities to increase efficiency of the magnetic field exposure on tumor cells by extending a frequency range of the therapeutic magnetic field in a low-frequency region compared to solutions disclosed in Applications WO20171751 16 and US20170014637A1 , as well as to combine low-frequency and high-frequency exposure and pulse variations and modulations thereof.

[022] In general, such a combination of features defines the novelty and inventive level. Magnetic connectivity of coils in combination with the extended frequency range and pulse character of producing exposure on tumor cells allow for, in this solution, improving efficacy and comfort of treatment based on both the significant increase in the value of magnetic induction and substantial reduction of current in coils and power consumption, thereby reducing the weight of batteries to the size of conventional AA or AAA, and as a result increasing the duration of a continuous procedure without recharging batteries. In this case, to magnetically connect the coils, an elastic ferromagnetic film or a metallic glass film may be used. Formation of a magnetic conductor in this manner allows for producing elastic inductors that would significantly improve comfort during the long-lasting application thereof. Moreover, metallic glass is characterized by extremely high electromagnetic radiation shielding capacity.

[023]. In addition, the system’s inductive elements in this configuration provide the required bandwidth of exposure and a combination of low- and high- frequency exposure in the pulsed and continuous modes.

[024] All above possibilities are accounted in a preferred embodiment of the system in which a generation means additionally includes a storage (4) with recorded pulse parameters being effective for treating specific tumor types. This storage is connected via a control device (6) (processor) to a DAC (5) programmable pulse driver the output of which is connected to an electromagnetic coil switch (2), with this switch being programmable. [025]. In addition to that, the extended range of exposure to improve treatment efficacy requires supplementary control, and, thus, the medium with recorded pulse parameters being effective for treatment of specific types of tumors is provided.

[026]. This medium stores characteristic parameters of the shape and frequency of pulses with respect to each tumor type which effectively suppress the growth of a specific type of a tumor. These data are derived from experiments and are stored in the database. Respective parameters via the control device (processor) are supplied to the programmable pulse driver (DAC) the output of which is connected to the electromagnetic coil switch. Therefore, the treatment efficacy is additionally enhanced due to effective exposure within a broad range of frequencies and combinations thereof in the magnetic field pulses.

[027] In accordance with this invention, to treat tumors and conduct most comfortable lengthy procedures, a new inductor was developed to include, at least, two orthogonal pairs of opposite coils (13, 14) enclosing a part of a head (1 1 ) in which a tumor (12) is located, with the coils being connected by a common magnetically conductive layer (15) and coupled in series to the generation means (16)

[028]. It is appropriate to use such an inductor for treating brain tumors. In this case, the coils enclose a human head in which a brain tumor is located. Such coils are not heavy, while they induce a rather effective field within the mentioned entire range, are easily integrated in any headgear and in combination with the compact control unit and power supply elements which may be simply disposed in a pocket cause no discomfort in the process of lengthy procedures.

[029] One more improvement consists in adding two more orthogonal pairs of opposite coils offset relative to the axis of first two pairs by an angle within a range of 30-60 degrees. Such a configuration of volumetric coils increases treatment efficacy and provides operation simultaneously in two modes, for example, in the mode of suppressing tumor growth and in the mode of stimulating the body immune reserves.

BRIEF DESCRIPTION OF DRAWINGS [030]. Fig. 1 illustrates an embodiment of the system equipped with plurality of coils disposed on the inside surface of a helmet or a headgear configured for treating a brain tumor and comprising a control device and a power supply unit and also a communication line with an external system, a hospital and a global database.

[031 ]. Fig. 2 illustrates a scheme of a comfortable head inductor with four coils (two pairs of orthogonal coils) and a portable self-contained control system.

[032] Fig. 3 illustrates an embodiment of the inductor with two additional pairs of orthogonal coils offset relative to each other.

DESCRIPTION OF THE SYSTEM IN THE STATIC MODE

[033]. Referring to Fig. 1 , a system for exposing a tumor to the magnetic field comprises an inductor section equipped with a plurality of electromagnetic coils (1 ) disposed on the inside surface of a partially spherical headgear and enclosing a head and a tumor area. Outputs of these coils are connected to a current generation means (2) to excite magnetic fields in coils inducing a therapeutic magnetic field for performing treatment in the tumor area.

[034] On the outside, coils (1 ) are connected by magnetic conductors (3) which may serve as a shield or an external electromagnetic protection. A generator section is made in the form of a pulse generator having a pulse repetition frequency of 2.5 - 1 ,000 Hz and a pulse frequency of 0.2 - 500 kHz. In this case, a magnetic field with induction of 0.1 - 100 mT is excited in coils.

[035]. The current generation means additionally comprises a medium (4) with recorded pulse parameters being effective for specific types of tumors. This storage (4), via the control device (6) (processor), is connected to the DAC programmable pulse driver (5) the output of which is connected to an electromagnetic coil switch (2), with the switch being programmable. In this case, all units are connected to the self-contained power supply (7). The control device (6) also communicates, via a wireless and Internet or other network (8), with an Information and Clinical Center (9), with the control device maintaining a database containing TTF parameters for different types of cancer (10) or communicating with said database.

DESCRIPTION OF SYSTEM OPERATION [036]. The system operates as described hereinafter.

[037] Subject to the clinical examination conducted in a Clinical Center (9), a physician identifies a location, an affected area size and a type of the cancer which induced tumor formation and refers a patient for the procedure. The Clinical Center preliminary conducts a research to identify parameters of the effective magnetic exposure to suppress tumor cells of different cancer types by using such methods, for example, as in https://www.novocure.com/our- pipeline/#clinical-trials, exclusively for magnetic fields and, according to the present invention, in the extended frequency range and pulse parameters of the magnetic TTF.

[038]. These research data are used to establish a TTF (10) database the date from which may be requested and delivered via available communication channels (8) to control units (6) of individual therapeutic devices and transferred to local storage (4) thereof. The physician also programs the procedures in accordance with the Clinical Center’s advices.

[039]. By a commencing procedure signal, the control unit (6) communicates the preset parameters from the storage (4) to the DAC programmable pulse driver (5) an output of which is connected to the programmable switch (2) of electromagnetic coils (1 ). In this case, the respective coils (1 ) induce a respective magnetic field of the preset orientation and induction. As a result, an array of magnetic coils (1 ) induces a 3-D therapeutic magnetic field in the part of a body (in the head area) where the tumor is located. Such a configuration has the advantage of having coils magnetically connected by a magnetically conductive layer (3) on outside thereof. This allows for achieving a substantial increase in induction, while significantly reducing energy consumption. In addition, this increases therapeutic capacities by both increasing procedure duration and comfort and by extending a range of the therapeutic intervention based on using both low frequencies and combining various (low-frequency and mid-frequency suppressing and stimulating) effects of exposure over the entire procedure duration, for example, during the course of the day. Therefore, the provided system may use both all TTF capacities and all therapeutic capacities of the low-frequency pulsed magnetic therapy both in the sphere of tumor growth suppression and in the sphere of the immune system stimulation, blood viscosity reduction, blood circulation improvement, etc., and also increase the procedure duration and provide combined effect over the entire procedure.

DESCRIPTION OF THE INDUCTOR EMBODIMENT

[040]. One of the embodiments of the present invention supplementing and developing features of the invented method is an inductor shown in Fig. 2, comprising, at least, two orthogonal pairs of opposite coils (13, 14) enclosing a part of the body, for example, a head (1 1 ) in which a tumor (12) occurred, with the opposite coils being coupled in series and connected by a common magnetically conductive layer (15).

[041 ] The advantages of this structure consist in inducing a rather intensive magnetic field by coils in combination with the magnetically conductive layer and a substantially increasing magnetic induction. In this case, the inductor bandwidth is maintained both in low-frequency and mid-frequency ranges.

[042] A serial connection of opposite coil pairs, similar to Helmholtz coils, provides actually uniform magnetic field throughout the entire volume, i.e. throughout the entire depth of the selected body part.

[043]. In addition to that, a large surface area covered by the coils and flexibility thereof result in the minor change in the form thereof and adaptation thereof to the body part surface. To treat brain tumors, this structure may be easily integrated in the headgear without causing discomfort during a lengthy use.

[044] Said coils (13, 14) are connected to the portable generation means (16) generating current pulses to excite a magnetic field in said coils (13, 14). The control device (17) is configured to control the procedure through a specific program to be preset or selected by the physician from a set of programs stored in the data storage device (18).

[045]. Said generation means is portable and easily fits in an outerwear pocket without causing discomfort and attracting attention of others. Cylindrical batteries (19) are used as a power supply (19).

[046]. The operation of the device is similar to that shown in Fig. 1.

EMBODIMENTS

[047] In a particular embodiment implemented as a mockup, four AAA cylindrical batteries with a capacity of about 2,000 mA/h were used. [048]. Coils were wound using 0.3 mm enameled copper wire

[049] Waveforming resistance - 50 Ohm

[050]. A unit of the UniSPOK-D magnetotherapeutic device was used as a generation means

[051 ]. Current consumption - / = 70 mA

[052] Induction - H = 0.5÷0.7 mT

[053]. Running time - 6 hours.

[054] A magnetically conductive coating applied using an amorphous metal film (METALIC GLAS). For comparison, when a frame was coated with metallic glass, the current consumption reduced 2-fold, while induction increased 12-fold.

[055]. To further develop functionality and enhance combined effect, the structure may be supplemented with two more orthogonal pairs of opposite coils offset relative to the axis of first two pairs by an angle ranging from 30 to 60 degrees. It is most preferable, by an angle of 45 degrees. In such cases, two independent types of effects of magnetic field exposure on the tumor and surrounding tissues may be produced.

[056]. Therefore, the claimed system and inductor possess new features which taken together produce a new technical result, i.e. they are novel and nonobvious for those skilled in the art.

[057] The system and inductor may be manufactured commercially from suitable materials and components, i.e. may be industrially applicable.

Claims

1. A system for producing effects on a tumor by exposing to magnetic field comprising an inductor section equipped with a plurality of electromagnetic coils disposed on a part of a body surface and surrounding a tumor area, and connected to a current generation means configured to excite magnetic fields in coils inducing a therapeutic magnetic field (TMF) in the tumor area, characterized in that on their outside said coils are interconnected by magnetic conductors, and a generator is made in the form of a pulse generator having a pulse repetition frequency of 2.5÷1 ,000 Hz and pulse frequency of 0.2÷500 kHz exciting the magnetic field with induction of 0.1 ÷ 100 mT.

2. The system according to claim 1 , characterized in that magnetic conductors are made in the form of a magnetically conductive layer.

3. The system according to claim 1 , characterized in that magnetically conductive layer is made from a ferromagnetic composite.

4. The system according to claim 1 , characterized in that magnetic conductors are made from amorphous metallic glass.

5. The system according to claim 1 , characterized in that the generator is made in the form of a pulse generator with a pulse repetition frequency of 2.5÷1 ,000 Hz and pulse frequency of 0.2÷500 kHz.

6. The system according to claim 1 , characterized in that a generation means additionally comprises a storage with recorded parameters of pulses being effective with respect to specific types of tumors, with the generation means being connected via a control device (processor) to a programmable pulse driver (DAC) an output of which is connected to the electromagnetic coils switch.

7. The system according to claim 1 , characterized in that the generator is coupled to electromagnetic coils via a programmable switch.

8. An inductor for the system according to claim 1 comprising a plurality of electromagnetic coils connected to the generator and disposed on a part of a body surface and surrounding a tumor area, characterized in that the inductor comprises, at least, two orthogonal pairs of opposite coils enclosing a part of the body in which the tumor is located, with the coils being coupled in series and being covered from the outside by a common magnetically conductive layer.

9. The inductor according to claim 8, characterized in that coils surround a human head in which the brain tumor is located and are disposed in a headgear.

10. The inductor according to claim 8, characterized in that it additionally comprises at least two more orthogonal pairs of opposite coils offset relative to the axis of first two pairs by an angle within a range of 30-60 degrees.