WO2021071373A1

WO2021071373A1 - Wireless electrostimulating applicator, method for generating electrostimulating pulses and use of the system for a pain therapy

Info

Publication number: WO2021071373A1
Application number: PCT/PL2020/050074
Authority: WO
Inventors: Siddarth AGRAWAL; Preeti AGRAWAL; Bartłomiej BARTOSZEWICZ; Piotr PRUCHNICKI; Mateusz SZMIT; Anil Kumar AGRAWAL; Waldemar GOŹDZIK; Jerzy Rudnicki
Original assignee: Uniwersytet Medyczny Im. Piastów Śląskich We Wrocławiu,
Priority date: 2019-10-10
Filing date: 2020-10-09
Publication date: 2021-04-15
Also published as: EP4041378A1; EP4041378A4; PL431427A1

Abstract

The first object of the invention is a wireless electrostimulating applicator, wherein the electrostimulating applicator includes an actuating module containing a module power supply system, a communication and control system and actuating system, the system further includes an application which controls the operation of the electrostimulating applicator, characterized in that the power supply system of the electrostimulating applicator contains a lithium-polymer battery (1) connected to the battery wireless charging system (2) which is connected to the voltage stabilizer of 3,3V (4), converter increasing the voltage to +95V (5) and a battery voltage measurement system (3), wherein the battery voltage measurement system (3) is connected to a microcontroller (6), the communication and control system includes a control microcontroller (6) which communicates via BLE interface (8) with the software on a PC or mobile device and the actuating system includes a set of controlled electric current sources (7), generating stimulation currents of adjustable intensity from which the electric current is directed to the electrodes (10), with which the skin resistance control system (9) coupled with the microcontroller is connected (6), wherein the stimulation current, generated by the actuating system, is in the form of pulses with an amplitude from -6mA to 6mA and repetition frequency from 1Hz to 200Hz. Moreover, the invention also relates to a method of generating electrostimulation pulses, a transdermal electrostimulation system, and the use of the pain therapy system.

Description

Wireless electrostimulating applicator, method for generating electrostimulating pulses and use of the system for a pain therapy

The first object of the invention is a wireless electrostimulating applicator for electrostimulation, which aims to stimulate the appropriate places in the human body with electric current, using the knowledge of acupuncture. The second object of the invention is a method of generating electrostimulating pulses based on application data collected from various sources, which allows to determine the optimal parameters of the electrostimulating applicator. The third object of the invention is a transdermal electrostimulation system comprising an electrostimulating applicator. The fourth object of the invention is the use of the system for the treatment of pain, especially post-operative pain in patients after inguinal hernia surgery or perinatal pain.

Acupuncture, as a therapeutic practice, derives from Far East countries. It has been practiced for over 2,500 years. It is used in a number of diseases. In 2002, the World Health Organization (WHO) published a report titled "Acupuncture. Review and Analysis of Reports on Controlled Clinical Trials". It contains information on clinical trials performed with the use of acupuncture techniques, including, which is particularly important, diseases, symptoms or conditions for which it has been proven - through controlled trials - that the use of acupuncture produces the desired and effective therapeutic effect, such as: adverse reactions to radiotherapy and/or chemotherapy, allergic rhinitis (including hay fever), biliary colic, depression (including depressive neurosis and depression after stroke), dysentery, menstrual pain, epigastric pain (also acute in peptic ulcer disease, acute and chronic gastritis and gastrospasm), facial pain (including craniomandibular disorders), headache, hypertension, hypotension, knee pain, leucopenia, lower back pain, fetal malposition, morning sickness, nausea and vomiting, neck pain, pain in dentistry (including toothache and temporomandibular dysfunction), periarticular shoulder inflammation, post-operative pain, renal colic, rheumatoid arthritis, sciatica, dislocation, stroke, tennis elbow.

In 1997, the National Institutes of Health (NIH, National Institutes of Health) accredited acupuncture as an effective treatment for post-operative pain, toothache, nausea and vomiting (induced by chemotherapy or pregnancy) and promising to alleviate menstrual pain, tennis elbow and abdominal pain based on available clinical evidence (Acupuncture, 1998; Morey, 1998; Wootton, 1997). In 2016, NIH-NCCIH (National Center for Complementary and Integrative Health) updated the clinical use of acupuncture according to research data, confirming its effectiveness in treating pain, including back and neck pain, osteoarthritis and knee pain as well as headaches (Wang, H., Yang, G., Wang, S., Zheng, X., Zhang, W., & Li, Y. (2018). The most commonly treated acupuncture indications in the United States: a cross-sectional study. The American Journal of Chinese Medicine, 46(07), 1387-1419; Med Clin (Bare). 2016 Sep 16;147(6):250-6. doi: 10.1016/j.medcli.2016.02.029. Medical indications for acupuncture: Systematic review).

The healing effect in acupuncture is achieved by inserting special silver or gold needles at specific body points that exert stimulus action on the peripheral and central nervous system, stimulating nerve endings. Acupuncture has an analgesic and healing effect. It improves blood circulation in the capillaries. This method is used to treat a wide range of diseases and pain conditions, as well as in inflammation, paralysis, and epilepsy. Electroacupuncture is a type of classical acupuncture in which strictly defined electrical stimuli support the stimulation of the body's characteristic points. Two types of electroacupuncture can be distinguished here. The first one uses needles inserted into the body of a patient. The second in which electrostimulation is performed transcutaneously. The second method is more desirable due to the lack of interference with the patient's body; namely, no piercing of the skin is needed. Research shows that stimulation with electrical impulses in appropriate areas of the body is widely effectively used in the treatment of, among others, high blood pressure, obesity, infertility, or depression.

There is a known device for electrostimulation of characteristic points on the human body KWD-808 L by SI NIC. This device has many functions, including electroacupuncture. The illustrated device is a stationary device; therefore, it cannot be used in patients for a cyclic therapy for an extended period of time, e.g., one month at specific intervals, e.g., every few hours. This device is not portable and thus cannot be used for long-term electroacupuncture treatments.

Also, there is known a medical device for electrotherapy called AWQ-104L, which is also a stationary device that does not allow long-term treatment in specific cycles.

A product called ECO20 ECOSTIM is another commercially available device. The device can control from 2 to 8 electrostimulating electrodes, depending on the wiring used. The operating parameters are set manually by the user, but the device does not allow for their automatic selection. The possibility of conducting electrostimulation is limited to the frequency of 150Hz only.

Another known electrostimulation device is TENS JUMPER JPD-ESlOOz. It exists in the form of two devices connected to each other by means of a flexible polymeric joint containing electric wires connecting both devices. One of the devices in the pair includes circuits for communicating with an external control device through an application. The application allows to control the actuating module and to program the operating mode. Additionally, the device is equipped with a miniaturized battery, enabling charging via USB and eliminating the need for a regular battery replacement.

The Polish patent description PAT.165804 describes a method of stimulating biologically active acupuncture points to which stimuli in the form of pulse bursts are applied. These bursts are repeated at a frequency of 5 Hz ± 30%, wherein the filling factor is 0,5-20%, i.e., the pulse burst duration tp is equal to half of the burst repetition period Tp. The pulses filling the burst have a frequency of 3.5 kHz with ± 30%, wherein the width of a single ti pulse is 12 ps ± 30%, wherein these pulses are spike pulses. The maximum voltage amplitude on 5000 W load is 125 V ± 30%, and the maximum current amplitude is 25 mA ± 30%.

The patent application no. US2009192406 describes an electroacupuncture system for measuring and acting on the energy balance of a meridian in a patient. The system uses a pressure-sensitive probe connected to the potential source and a return path contact. The probe and contact are used to diagnose and treat a patient's energy meridian imbalance. The selection of electrostimulation parameters is based on the interpretation of the measured values of the energy balance. The presented device is a handy device for performing manual stimulation at specific single points; therefore, it is not suitable for long-term therapy at specified intervals without the need to visit a treatment center.

Another electrostimulation system is known from the international PCT application no. WO2016113661A1. The system includes an electrode patch and a mobile device. The condition of a patient is monitored by means of a mobile device and a patch with electrodes. After receiving information that the patient is experiencing, e.g., a headache, the mobile device communicates wirelessly with electrodes in the patch, causing an electrostimulating effect, thus reducing the level of experienced pain.

The Polish patent no. PAT.228476B1 describes a device for a transdermal therapeutic electrostimulation having an actuating module containing a module power supply system, a communication, and a control system as well as an actuating system. The built-in power supply includes a lithium-ion battery connected to the battery charging system, which is connected to a voltage stabilizer of 3.0V and a converter increasing the voltage to +30V; the communication and control system includes a control microcontroller communicating via USB interface with the software on a PC, and the actuating system contains a electric current digital-to-analog converter in the range from 0 m A to 10 mA, from which the electric current is directed to the electrodes to which the output voltage control system coupled with the microcontroller is connected, while all electronic elements included in the actuating module are installed on both sides of a four-layer printed circuit board.

The technical problem set for the present invention is to provide an applicator for electrostimulation that will adhere directly to the skin, and that will be characterized by simple construction, that will be small in size which will allow the user to wear it continuously over an extended period of therapy, and in addition, that will provide an electric signal with adjustable characteristics, intensity, frequency or polarity, automatically provide the therapy over a multi-day period without the need for charging and that will inform about the lack of contact with the user's skin and register the battery voltage and resistance of contact with the skin during the therapy period. Additionally, the applicator should be able to charge wirelessly. The applicator should also be able to be remotely controlled using a mobile device or a PC. Moreover, it should be possible to control either a single applicator or groups of applicators. The applicator should also be of a single body structure, with no wires connecting it to other applicators. It should also be possible to independently or automatically adjust the electrostimulation characteristics on the basis of data collected by the working applicators system, and the use of applicators for electrostimulation should reduce the doses of analgesic pharmaceuticals. The technical problems mentioned above have been solved by the present invention.

The first subject of the invention is a wireless electrostimulating applicator which includes an actuating module containing a module power supply, a communication and control system and actuating system. Further, the system includes an application for controlling the electrostimulating applicator operation, characterized by the fact that the power supply system of the electrostimulating applicator contains a lithium-polymer battery connected to the wireless battery charging system, which is connected to voltage stabilizer of 3.3V, converter increasing the voltage to +95V and a battery voltage measurement system, wherein the battery voltage measurement system is connected to a microcontroller. The communication and control system includes a microcontroller that communicates via BLE interface with software on a PC or a mobile device, and the actuating system includes a set of controlled electric current sources generating a stimulation current of a regulated intensity. The electric current is then directed to the electrodes connected to the skin resistance control system coupled with a microcontroller. The stimulation current generated by the actuating system is in the form of pulses with an amplitude from -6mA to 6mA and a repetition frequency from lHz to 200Hz.

In a preferred embodiment of the invention, the wireless battery charging system operates in the Qj standard. Qj standard is a wireless charging system for electronic devices commonly used in many mobile devices. A mobile device should be understood as an electronic device that allows for processing, receiving, and sending data without the need to maintain a wired connection to the network. A user can move the mobile device without the need to involve additional means.

On the other hand, wireless communication implemented in the popular Bluetooth Low Energy (BLE) standard enables easy control of a single applicator or a group of applicators using mobile devices.

In another advantageous embodiment of the invention, the actuating system enables to determine the duration of the electric current pulses or polarization of the pulses.

In a further preferred embodiment of the invention, the set of controlled electric current sources comprises at least two electric current sources.

The second object of the invention is a method for generating electrostimulating pulses in the electrostimulating applicator as defined in the first object of the invention, based on the collected application data from at least one electrostimulating applicator, data introduced by the user on a PC or mobile device, and user data generated and processed by the mobile device, wherein according to the method: a) the electrostimulation parameters are taken from the electrostimulating applicator and sent to the collecting device, b) data introduced by the user on a PC or mobile device is downloaded and sent to the collecting device, c) raw data is downloaded from the accelerometers in a mobile device and processed by existing technologies and sent to the collecting device, d) or the data generated by a smartwatch or smart band devices connected to the mobile device is downloaded and sent to the collecting device, e) the data collected in steps from a) to c) or to d) are processed with the use of artificial intelligence and machine learning algorithms on the central server, which, based on them, conclude about the recommended parameters of the electrostimulating applicator, f) the recommended operating parameters obtained in step e) are sent to the mobile application, g) parameters sent in step f) are sent to the electrostimulating applicator or electrostimulating applicators via the communication system of the electrostimulating applicator to the control system of the electrostimulating applicator, h) the electric signal with the recommended operating parameters, generated in the actuating system of the electrostimulating applicator, is supplied in the form of pulses with a frequency from lHz to 200 Hz and amplitude from -6mA to 6 mA to the application electrodes. In a preferred embodiment of the invention, the electrostimulation parameters taken from the electrostimulating applicator include electrostimulation parameters, preferably: stimulation duration, pause time between stimulations, cycle duration, stimulation pulses current intensity, pulses duration, pulse repetition frequency, electrostimulation current intensity, electrostimulation pulses polarization, data generated by the electrostimulating applicators, preferably the user's skin resistance value or battery charge level.

In another preferred embodiment of the invention, the data introduced by the user in a PC or mobile device include biometric data of the user, preferably gender, age, weight, height, BMI, data on the user's health condition, preferably data on current and past diseases, medications taken, discomfort, disease symptoms duration, applicator location data, user-perceived pain or other discomfort scale assessment, preferably on VAS or other scales, user-perceived comfort or discomfort scale associated with current electrostimulation parameters.

In a further advantageous implementation of the invention, the raw data collected from the accelerometers in the mobile device and the processed data include data on the user's current activity, preferably on motion, the number of steps taken, the number of floors climbed.

In yet another preferred embodiment of the invention, the data generated by smartwatches or smart bands coupled to the mobile device include data on the user's current heart rate and activity, preferably on motion, the number of steps taken, the number of floors climbed.

In another preferred embodiment of the invention, the recommended operating parameters of the electrostimulating applicator include cycles duration, stimulation pulses current intensity, pulses width, pulses repetition frequency, stimulation duration, pause time between stimulations.

In yet another preferred embodiment of the invention, the recommended operating parameters are modified by the user.

The method of data collection and processing is carried out on a hardware and software platform operating in the client-server architecture in which the application installed on a PC or in the user's mobile device acts as a client and serves to collect application data and controls the operation of electrostimulating applicators, using the operating parameters sent from the server. The server collects data from applications installed on a PC or in a mobile device and processes them using artificial intelligence and machine learning algorithms to determine the optimal operating parameters of electrostimulating applicators adapted to the needs and conditions of the user, which then sends it to the application installed on the PC or in the mobile device. Communication between the application installed on the PC or in the mobile device and server takes place via the Internet using VPN tunneling. The third object of the invention is a transdermal stimulation system comprising at least one electrostimulating applicator as defined in the first object of the invention, the operation of the electrostimulating applicator being controlled by the method defined in the second object of the invention.

In a preferred embodiment of the invention, the system comprises at least two electrostimulating applicators as defined in the first object of the invention, the electrostimulating applicators being controlled independently of each other.

In another preferred embodiment of the invention, the electrostimulating applicators operate independently of each other, the applicators forming at least one group of electrostimulating applicators, the group comprising no more than four electrostimulating applicators.

In yet another preferred embodiment of the invention, the system comprises at least two groups of electrostimulating applicators, the groups being controlled independently.

The fourth object of the invention is the use of the system as defined in the third object of the invention for the treatment of pain.

Preferably, the invention is used in the treatment of post-operative pain in patients after inguinal hernia surgery.

In another preferred embodiment, the invention is used in the treatment of perinatal pain.

The wireless system for transdermal therapeutic electrostimulation, containing an electrostimulating applicator, occupies a small area due to the use of small components, which reduces its weight and makes it comfortable to wear for a longer period of therapy. The lithium-polymer battery used ensures long operation of the device, which makes it possible to conduct therapy for several days without the need to recharge. The applied microcontroller, together with a set of controlled electric current sources with adjustable stimulation current intensity, pulses duration, repetition frequency, and variable polarity, allows for any shaping of electric flows and signals, thanks to which a wide range of electroacupuncture therapies can be conducted. The wireless communication system used allows for easy and quick control or reprogramming of the applicators. The wireless charging system allows to create a fully hermetic module, resistant to environmental factors, especially moisture. According to the solution, the system enables real-time parameters modification of the applicators operation through an application located on a mobile device and based on data generated by a processing mechanism based on artificial intelligence and machine learning mechanisms. When a discomfort/problem is identified, the stimulation is automatically intensified/current parameters are changed to improve the therapy's effect. Moreover, it is possible to automatically detect, in the event of loss of contact between the skin and the applicator, recommended appropriate sites of stimulation, and adjust the output intensity based on the applicator's initial measurement.

The embodiment of the invention was presented in the drawing, where Fig. 1 shows a block diagram of an electrostimulating applicator, Fig. 2 - a diagram of a pulse generating system, Fig. 3 is a diagram of a stimulation signal, Fig. 4 a pain sensation after hernia operation assessed in the VAS at hospital discharge by the patients who differ from each other by the intervention type, Fig. 5 total dose of morphine consumed by patients differing in the type of intervention and the result of the analysis of variance and multiple comparisons (Tukey's post-hoc tests) in the therapy after hernia surgery, Fig. 6a- 6c the marginal values of perceived pain (average and their 95% confidence intervals) and assessment of the effect of treatment (a), time (b) and interaction Group Time (c) after hernia surgery, Fig. 7 correlation diagram between the dose of morphine and perceived pain, the value of the Pearson correlation coefficient and the equation of the regression line after hernia surgery, Fig. 8 age of women in labour with different types of intervention and the result of the analysis of variance and multiple comparisons (Kruskal-Wallis tests), Fig. 9 pain sensation assessed on the VAS scale at the beginning of the test in women with different types of intervention and the result of the analysis of variance and multiple comparisons (Kruskal-Wallis tests), Fig. 10 pain sensation assessed on the VAS scale after 30 minutes of the test in women with different types of intervention and the result of the analysis of variance and multiple comparisons (Kruskal-Wallis tests), Fig. 11 pain sensation assessed on the VAS scale at the end of the trial in women with different types of intervention and the result of the analysis of variance and multiple comparisons (Kruskal-Wallis tests), Fig. 12 exemplary arrangement of the applicators on the patient's body, where A1-A4 represent successive electrostimulating applicators AE, Fig. 13 a block diagram of electrostimulating pulses generation.

Example 1. Construction of an electrostimulating applicator

Fig. 1 shows a block diagram of actuating module of an electrostimulating applicator AE which distinguishes three main groups of elements, i.e. systems related to powering the entire device which include a lithium-polymer battery 1, a wireless battery charging system 2, battery voltage control system 3, voltage stabilizer 3,3V 4 and converter increasing the voltage to +95V 5; communication and control systems comprising a control microcontroller 6 that communicates wirelessly with software on a PC or in a mobile device via the BLE interface 8, wherein the task of the microcontroller 6 is to control all the other systems and to send stimulation pulses with specific parameters; actuating systems including controlled, bipolar electric current sources giving the current with an amplitude of +/-6 mA 7 (Fig, 2), which generate an electric current of precisely determined intensity and which are directed to the outputs of the application electrodes 10, wherein the signal from the electrodes goes through the skin resistance control system 9 to the microcontroller 6. a) Power supply system

The electrostimulation applicator is characterized by small dimensions, diameter less than 36 mm, thickness less than 12 mm. Hence, it was extremely important to choose an appropriate battery 1 due to its size and electrical capacity. Such properties are characteristic for lithium-polymer batteries. The capacity of battery 1 is related to its volume. Therefore, the same capacity can be obtained in the case of a battery with a larger surface area but thinner or thicker with smaller dimensions. The applicator for electrostimulation uses a battery 1 with a capacity of o 210 mAh. A larger battery would allow the electrostimulation module to operate longer but will significantly increase its size, which is definitely a disadvantage. Due to their specific properties, lithium-polymer batteries require an appropriate, special charging system 2. For this purpose, a charging system 2 operating in Qj standard is a wireless charging system for electronic devices commonly used in many mobile phones. The possibility of a wireless charging requires the use of a special receiver integrated circuit and a receiving coil. The receiving coil is made of a properly wound copper wire and a ferrite shielding pad. The receiving coil must be located as close to the outer casing as possible to ensure efficient power transfer from the charger system. For this reason, its shape and dimensions, i.e., diameter and thickness, must allow it to be placed inside the applicator. The use of the wireless charging system 2 allows for a complete encapsulation of the electrostimulation module. In this way, it is possible to better protect the electronic systems against the influence of environmental factors, especially moisture. The entire module will be placed in a sealed silicone casing. Only the stimulation electrodes 10 will protrude to the outside.

The dimensions are also important for a converter 5 generating high voltage due to the limited space. Additional requirements are:

• possibility of obtaining the maximum output voltage up to 95 V,

• possibility to adjust the output voltage,

• high efficiency of the system, reducing energy losses. b) System generating stimulation pulses 7

The system that is responsible for the generation of stimulation pulses (Fig. 2) consists of two identical branches. One of them is connected to the stimulating electrode, the other to the reference electrode, in the system of output electrodes 10. Each branch contains:

• high voltage pulses keyer system, • voltage-controlled electric current source,

• electric current source keyer system.

This topography allows for a generation on the application electrodes 10 of pulses of variable polarity and precisely determined stimulation current CC1 or CC2. The system can generate pulses with a frequency from lHz to 200Hz. The resistors connected in-line to the electrodes 10 increase the system's output impedance; their presence protects the user's skin and electronic components from the flow of too high electric current in the event of a failure of the switching system. Simultaneously, the voltage decrease on one of the resistors allows to measure the skin resistance. c) Microcontroller 6

The most important element of the device is the microcontroller 6, which controls the operation of the entire applicator. This system is characterized by a very low power consumption during operation, which allows to construct a device that works for a long time without the need to recharge the battery 1. The microcontroller 6 is an electronic system that contains a processor that executes a program stored in the memory and many additional systems that allow for the implementation of various additional functions, as described below.

One of these functions is the measurement of the voltage of the battery through the voltage measurement system 3. The measured value is stored in the non-volatile EEPROM memory. As a result, it is possible to follow the discharge process of the battery 1 and to forecast the applicator operating time.

Information on the resistance of the electrode 10 connection with the skin is also stored in EEPROM. The recorded information allows to assess the quality of the connection and to react in case of a deterioration of the contact parameters of the electrodes 10 with the skin. The resistance measurement by circuit 9 allows to regulate the voltage of the stimulation pulses. In case of a low resistance, when the electrodes 10 adhere well to the skin, the voltage from the converter 5 is reduced, which makes it possible to reduce the energy demand.

A quartz oscillator creates a precise clock working at a frequency of 32.768 kHz. This system, together with the timer contained in the microcontroller 6, measures the time between successive stimulation cycles.

The system activity is signaled by two LED diodes located in the applicator casing: red and green. Continuous lighting of the red diode means charging of the battery 1. During stimulation, the diodes flash. The red diode's flashes indicate the sending of electric current pulses to the electrodes 10, but in a situation where the skin resistance is high. The flashes of the green diode occur at low, optimal skin resistance. In this way, without reading the data from the applicator, it is possible to quickly see whether the electrodes 10 of the applicator are in good contact with the skin.

The applicator has a special operating mode that facilitates its placement on the user's body. In this mode, the device sends stimulating pulses and simultaneously measures skin resistance. Information about the resistance is sent to the application and indicated by flashing LED diodes. At higher resistance values, the red LED flashes as the resistance between the electrodes 10 and the skin decreases, and the green diode starts flashing. Simultaneously, the flashing speed increases as the resistance decreases. This solution allows to place the applicators only on the basis of the light signals they send without the need to use an application. This proceeding mode significantly speeds up the procedure of mounting the devices. d) Bluetooth Low Energy communication module 8

According to the assumptions, the actuating module of the electrostimulation applicator communicates with the outside environment in the Bluetooth LE standard (communication system 8). A commonly used solution is the use of ready-made communication modules that are produced by many companies. Due to the parameters of communication modules available on the market, and especially the miniature dimensions, the ATSAMB11-ZR module from Microchip was selected. The transmission of information in the BLE standard takes place through services and associated characteristics. The first characteristic is used to read the applicator configuration; the first bytes are the identification string. The next ones are the applicator configuration read from its internal EEPROM memory. The configuration includes information about stimulation (frequencies electric current intensity, stimulation time). The third characteristic is used to control the applicator operation (turn on, turn off, start, stimulation stop). The fourth characteristic is used to transfer the stimulation configuration to the applicator. The fifth characteristic is intended to read the historical data collected by the applicator during stimulation regarding skin resistance and battery voltage.

Example 2. Stimulating signal

The design of the electrostimulation applicator with the features according to example 1 allows to control or program the stimulating signal waveform. The stimulating signal consists of electric current pulses repeated at fixed intervals. According to the assumptions, it is possible to influence many parameters of this signal. Fig. 3 shows an exemplary stimulating waveform and indicates which signal parameters can be changed. First of all, each signal consists of two stimulation cycles Cl and C2, which can be defined independently. In the cycle, it is possible to set the following operating parameters:

• cycle duration (Cl, C2), • stimulating pulses current intensity (CC1, CC2),

• width (duration) of pulses (BC1, BC2),

• pulse repetition frequency (it is unambiguously related to the repetition period (AC1, AC2)). Both stimulation cycles (Cl, C2) are repeated alternately for a fixed stimulation period. Stimulation period PI and the pause time between stimulations P2 are also set by the user by sending the appropriate configuration data from a mobile device or PC. An exemplary signal waveform is shown in Fig. 3a.

The first two parameters are:

PI - stimulation period (Fig. 3a)

P2 - pause time between stimulations (Fig. 3a)

These parameters are set by the user in the remote control or mobile application in the range of 1 - 60 minutes for the stimulation period and 5-720 minutes for pause time between stimulations.

The next 6 parameters (AC1, BC1, Cl, AC2, BC2, C2) define the type of stimulation by setting the stimulation cycle parameters (frequency, pulse width, cycle duration).

The last two parameters are the stimulation current:

CC1 - current intensity during the day,

CC2 - current intensity during the night.

Two intensity values were defined because preliminary tests showed greater sensitivity to electrical pulses at night, which means that the intensity of stimulation current during sleep has to be reduced.

Example 3. The method of generating electrostimulating pulses

The method of generating electrostimulating pulses is based on the collected data, and their processing using an application installed on a PC or user's AM mobile device and a central CS server that communicates with the application installed on a PC or AM mobile device via the Internet using VPN tunneling. The pulse generation method is shown in Fig. 13.

The application installed on a PC or the user's AM mobile device is used to collect data concerning one user, in particular data from DAP electrostimulating applicators, data entered by the user including biometric data, data concerning health, medications taken, and ailments as felt as well as data generated and processed via a mobile device (DAPL or DSS) and devices such as smartwatches or smart bands SS. The second use of the application installed on a PC or AM mobile device is to control the operation of AE electrostimulation applicators. The application uses for electrostimulation parameters generated by an artificial intelligence (Al) or machine learning (ML) algorithm working on a central server CS. The user has the possibility to modify the operating parameters of the AE applicator so as to minimize the level of pain and/or other ailments and maximize his comfort.

The central server CS has the function of collecting data from many applications installed on a PC or AM mobile device and processing the collected data using artificial intelligence and machine learning algorithms. The artificial intelligence and machine learning algorithms that can be applied include but are not limited to: expert system, linear regression model, logit regression model, decision tree, GLM model (Generalized Linear Model), GAM model (Generalized Additive Model), random forest, gradient boosting model, artificial neural network, deep artificial neural network, k-means method, SOM method (Self-Organizing Map).

Artificial intelligence and machine learning algorithms recommend optimal RPP working parameters, namely the values of the stimulating signal parameters as described in the second example, electrostimulation applicators AE for the user based on the user's data, in particular biometric data (gender, age, weight, height, BMI), data on the user's health (data on current and past illnesses, medications taken), data generated and processed by DAPL mobile device and smartwatch or smart band SS devices, data describing ailments, data on the location of applicators and the assessment of the scale of pain experienced by the user on the VSA scale or other. Raw data collected from accelerometers in the AM mobile device can also be used to determine the recommended operating parameters, such as data on the user's current activity, preferably regarding motion, the number of steps taken, the number of floors climbed.

The data collected from the AE applicator constitute the basis for Al and ML to generate the recommended RPP operating parameters. The data include electrostimulation parameters, preferably stimulation duration, pause time between stimulations, cycle duration, stimulation pulses current intensity, pulses repetition frequency, electrostimulation current intensity, the polarity of electrostimulation pulses, data generated by the electrostimulating applicators, preferably resistance value of the user's skin or the battery charge level.

The input of the artificial intelligence and machine learning algorithm takes a set of data as described above. They process the data in a way specific to the algorithm. The output of the algorithm shows the recommended RPP parameters of the AE electrostimulating applicators. The obtained recommended RPP operating parameters of the AE electrostimulating applicator are then sent to the applicator or applicators through the BLE 8 module, wherein, on the basis thereof, the control system generates an electrical signal in the actuating system in the form of pulses. The pulses characteristics are limited by the design of the AE applicator, as in the first embodiment. The pulse electrical signal generated in the actuating system of the electrostimulating applicator is fed to the electrodes 10. The recommended RPP operating parameters sent from the CS central server to the mobile application can also be modified by the user in order to individually and precisely select the operating parameters of the AE applicator.

The use of artificial intelligence and machine learning algorithms makes it possible to recommend to the user such electrostimulation parameters that will most effectively reduce the patient's pain or other ailments in therapeutic uses and contribute to the greatest comfort improvement. The user will be able to modify the applied electrostimulation parameters so as to minimize the level of perceived pain or other discomforts in the case of therapeutic uses and maximize his comfort. The recommendations take into account the needs and condition of the user, in particular his gender, age, weight, height, type and intensity of pain and/or other ailments, concomitant diseases, and variables describing the user's health, time of day/night, the impact of stimulation on the perceived pain level, in case of therapeutic uses, the user's skin resistance, the history of the user's electrostimulation parameters settings modification, the user's current heart rate, and the user's current activity level.

Example 4. System for electrostimulation

A dedicated application for mobile devices is used to control the operation of applicators AE for transdermal electrostimulation, according to the design from the first example. However, the control itself is carried out according to the method described in the third example. By using the BLE 8 communication standard, the application allows to search for AE modules (applicators) present in the area for AE stimulation. An appropriate screen allows to select by the user of up to four applicators operating together. It is also possible to create more than one group of applicators. Moreover, the formed groups of applicators can be independently controlled according to the method described in the third example.

In the next step, the AE applicator shall be placed on the body, and such information shall be introduced into the program. The most important step before starting the stimulation is to select the appropriate intensity of CC1 or CC2 stimulation current. The appropriate test mode screen allows to change the current intensity and informs about the quality of the AE applicator contact with the skin by measuring the resistance. The AE applicator should be positioned in such a location where the contact resistance of the electrodes 10 with the skin will be the lowest. In such conditions, the device uses the smallest stimulation voltage to obtain the proper stimulation. The voltage change results from the expression U=R*I, where U - current voltage, R - resistance, I - current intensity. An increase of resistance makes it necessary to increase the voltage in order to obtain stimulation with a correct intensity. For the user, this increases the comfort of use and, at the same time, reduces energy consumption.

After installing the applicator and determining the correct intensity of CC1 or CC2 stimulation current, it is necessary, in the next window, to determine the type of stimulation by selecting the appropriate stimulation sequence from the list in the application on the mobile device. This window also allows to define the duration of PI simulation and the time interval between successive P2 stimulations. An additional parameter setting the time of the beginning of the nighttime allows to reduce the current intensity during sleep.

A dedicated application for mobile devices also allows to control more than one electrostimulating applicator. All applicators included in the stimulation system operate autonomously after their activation, and it is not necessary to use them for application control.

Each of the AE applicators is an independent device that carries out a programmed stimulation cycle, e.g., according to the characteristics of the stimulating signal from the second example. In order to increase the effectiveness of the therapy, a greater number of applicators are used in different places on the user's body (Fig. 12). The group of applicators created in this way works simultaneously according to the same stimulation program, and at the same time, they start stimulation and simultaneously end the stimulation. Flowever, due to the different levels of sensitivity of the stimulated body points, each of the applicators in the group has an individually selected stimulation current intensity.

After the application of stimulators, the role of the mobile application is reduced to obtaining information about the current status of each applicator - it is possible to obtain information about the battery status and the resistance of the electrode connection with the skin. The application is also used in an emergency. If necessary, if the stimulation is too strong, the stimulation can be stopped immediately. Similarly, it is possible to start stimulation earlier if the pain sensation becomes too strong.

Example 5. Use of the system in pain therapy

The use of the system, as described in Example 4, enables effective pain therapy. a) The use of electrostimulation in the treatment of post-operative pain in patients after inguinal hernia surgery (Fig. 4-7)

Methodology

The prospective, randomized study included 35 patients, 6 women and 29 men, admitted to the University Teaching Hospital in Wroclaw, to the Department of General, Minimally Invasive, and Endocrine Surgery from November 2018 to May 2019. The patients were qualified for the Lichtenstein method of inguinal hernia plastic surgery. After surgery, all patients were connected to an infusion pump with PCA (Patient-controlled analgesia) function with morphine solution at a concentration of lmg/lml. No induction dose or base morphine infusion was administered. A single dose, possible for the administration to a patient in the PCA regimen, was 1 mg, with a limit of 10 doses in 4 hours. The lockout time was 15 minutes. Depending on the group to which a patient was qualified, electrodes emitting a current of 1.2-1.8 mA were then placed in cycles of 60 min stimulation/60 min break (Study Trial, ST1), electrodes generating subliminal pulses (Blind Test, BT1) or no electrodes were applied (Control Test, CT1). Next, for 24 hours, at four-hour intervals, the pain level was measured on the basis of the VAS scale (Visual Analog Scale) (Fig. 6), the number of breaths, saturation, blood pressure, heart rate, presence of nausea or symptoms of sedation. Upon disconnection of the infusion pump, the total morphine boluses administered by the patient were recorded (TMD, total morphine dose). Patients with recurrent hernias, respiratory or cardiac failure, and chronically treated with opioids were excluded from the study. The study was approved by the Bioethics Committee at the Medical University of Wroclaw (consent no. KB 599/2017). The scope and purpose of the study were carefully explained to each patient. Each patient expressed his willingness to take part in the study by signing an informed consent form.

The study involved 35 patients, including 6 women (17,1%) at the age of 27 to 88 years (average 58,7; standard deviation SD = 14.5 years). The results are presented in Table 1. Table 1. General characteristics of patients in randomized groups (hernia)

A group of patients

Feature (variable) ST1 BT1 CT1 P-value

_ N = 11 _ N = 13 _ N= 11 _

Gender: n % n % n %

Women 2 18,2% 1 7,7% 3 27,3% 0,445

Men _ 9 81,8% _ 12 92,3% _ 8 72,7% _

Age (years of age):

M (SD) 58,1 (17,3) 59,4 (14,7) 58,6 (12,3) _{Q g??}

Me [IQR] 57 [49; 70] 63 [42; 71] 60 [49; 68]

Min - Max 27 - 88 34- 76 36- 74 All three groups of patients were homogeneous in terms of gender and age structure (p > 0,05).

The level of perceived pain in the ST1 group was significantly lower than in the BT1 and CT1 group (p< 0,01). The difference was insignificant between ST1 and CT1 groups (p > 0,05). Similar differences occurred with total morphine dose (TMD) (Fig. 5).

The results of the two-way analysis of variance confirmed that the level of perceived pain after using the system according to the invention, in the study group (ST1) is significantly lower than in the others (Fig. 6a). All patients experienced the severest pain at the eighth hour after surgery (Fig. 6b), and no statistical interaction was observed between the type of treatment (Group) and measurement time (Time) - Fig. 6c

A positive, statistically significant correlation was observed between pain intensity and morphine doses (Fig. 7).

B) The use of electrostimulation in the treatment of perinatal pain (Fig. 8-11)

Methodology

The prospective, randomized study included 22 patients admitted to the Obstetrics and Gynecology Department of the Provincial Specialist Hospital in Wroclaw, Research and Development Center from February 2019 to May 2019. The inclusion criteria were as follows: (a) signed consent; (b) between 20 and 35 years of age; (c) planned vaginal delivery with a single pregnancy; (d) gestational age 37-42 weeks; (e) fetal apex presentation; (f) no obstetric or non-obstetric complications; and (g) dilation of the cervix C3 cm with regular contractions. The exclusion criteria were: (h) emergency delivery; (i) instrumental or CS delivery during labor; (k) history of electroacupuncture experience for pain relief; (I) wound scarring or inflammation at the application sites; and (m) the presence of a pacemaker. Patients qualified for vaginal delivery were randomly assigned to one of three groups: Group I (sham therapy, Blind Test 2 - BT2) - device generating subliminal electrical pulses, Group II (proper therapy, Study Trial 2 - ST2) - device generating the appropriate electrical pulses with appropriate parameters (intensity between 1 and 3 mA; frequency 2/100 Hz, in cycles of 30 min stimulation/30 min break); Group III (control, Control Test 2- CT2) - no devices connected. Next, for 24 hours, at four-hour intervals, the pain level was measured on the basis of the VAS scale (Visual Analog Scale), the number of breaths, saturation, blood pressure, heart rate, presence of nausea, or symptoms of sedation. The study was approved by the Bioethics Committee at the Medical University of Wroclaw (consent no. KB 27/2019). The scope and purpose of the study were carefully explained to each patient. Each patient expressed her willingness to take part in the study by signing an informed consent form. Results

The compared groups of women were homogeneous in terms of age and pain level at the beginning of the study (p > 0,05). Already after 30 minutes, after using the system according to the invention, the intensity of pain in the ST2 group decreased, and by the end of labor, it was lower than in the CT2 and BT2 groups and PBT2 (p < 0,05). The results are presented in Table 2.

Table 2. General characteristics of patients in randomized groups (perinatal pain)

CT2 ST2 BT2 Test

N = 7 N = 8 N = 7 P

Age 0,716

M ± SD 27,6 ± 2,0 26,9 ± 3,8 26,6 ± 2,4

Me [Ql; Q3] 28 [25; 29] 27 [24; 30] 27 [24; 28]

Min -Max 25-30 22-33 23-30

Pain intensification at the

0,542 beginning (VAS)

M ± SD 7,1 ± 1,3 7,9 ± 1,1 7,4 ± 1,3

Me [Ql; Q3] 7 [6; 8] 8 [7; 9] 7 [6; 9]

Min - Max 5-9 6-9 6-9

Pain intensification after

<0,001 30 minutes (VAS)

M ± SD 6,6 ± 0,8 3,8 ± 0,7 7,0 ± 0,8 Me [Ql; Q3] 7 [6; 7] 4 [3; 4] 7 [6; 8]

Min - Max 5-7 3-5 6-8

Pain intensification at the

<0,001 end (VAS)

M ± SD 6,0 ±0,8 2,9 ±0,8 6,9 ± 1,1

Me [Ql; Q3] 6 [5; 7] 3 [2; 4] 7 [6; 8]

Min - Max 5-7 2-4 5-8

Willingness to repeat the n % n % n % therapy:

100

Yes 0 0,0 3 42,9 <0,001

⁸ ,0

No 0 0,0 0 0,0 4 57,1

_ 100,

Not applicable 0 0,0 0 0,0

Claims

1. A wireless electrostimulating applicator, electrostimulating applicator comprising an actuating module containing a module power supply system, a communication and control system and an actuating system, the system further includes an application which controls the operation of the electrostimulating applicator, characterized in that the electrostimulating applicator power supply system comprises a lithium-polymer battery (1) connected to the wireless battery charging system (2) which is connected to the voltage stabilizer of 3,3V (4), converter increasing voltage of +95V (5) and battery voltage measurement system (3), wherein the battery voltage measurement system (3) is connected to a microcontroller (6), the communication and control system includes a control microcontroller (6) which communicates via BLE interface (8) with software on a PC or mobile device and the actuating system includes a set of controlled electric current sources (7), generating stimulation current of adjustable intensity from which the electric current is directed to the electrodes (10) with which the skin resistance control system (9) is connected and coupled with the microcontroller (6), wherein the stimulation current generated by the actuating system is in the form of pulses with an amplitude from -6mA to 6mA and repetition frequency from lHz to 200Hz.

2. The wireless applicator, according to claim 1, characterized in that the wireless battery charging system (2) operates in the Qj standard.

3. The wireless applicator, according to claim 1 or 2, characterized in that the actuating system allows to determine the electric current pulses duration (BC1, BC2) or pulse polarization.

4. The wireless applicator, according to claims 1 to 3, characterized in that the set of controlled current sources comprises at least two electric current sources.

5. A method of generating electrostimulation pulses in an electrostimulating applicator (AE), as defined in claim 1, on the basis of the collected application data derived from at least one electrostimulating applicator, data introduced by the user on a PC or mobile device, and user data generated and processed by the mobile device, wherein according to the method a) the electrostimulation parameters are taken from the electrostimulating applicator (AE) and sent to the collecting device (CS), b) data introduced by the user on a PC or mobile device (AM) is downloaded and sent to the collecting device (CS), c) raw data are downloaded from accelerometers in a mobile device (DAPL) and processed by existing technologies and sent to a collecting device (CS), d) or the data generated by a smartwatch or smart band (SS) device is downloaded and sent to the collecting device (CS), e) the data collected in steps from a) to c) or to d) are processed with the use of artificial intelligence and machine learning algorithms on the central server (CS), which on the basis of them conclude about the recommended operating parameters (RPP) of the electrostimulating applicator (AE), f) the recommended operating parameters (RPP) obtained in step e) are sent to the mobile application (AM), g) the parameters (RPP) sent in step f) are sent to the electrostimulating applicator or electrostimulating applicators (AE) via the communication system of the electrostimulating applicator (AE) to the control system of the electrostimulating applicator (AE), h) the electric signal with the recommended operating parameters (RPP) generated in the actuating system of the electrostimulating applicator (AE) in the form of pulses with a frequency from lHz to 200 Hz and amplitude from -6mA to 6 mA is supplied to the application electrodes (10).

6. The method, according to claim 5, characterized in that the electrostimulation parameters taken from the electrostimulating applicator (AE) include: electrostimulation parameters, preferably stimulation duration, pause time between stimulations, cycle duration, stimulation pulses current intensity, pulses duration, pulse repetition frequency, intensity of the electrostimulation current, electrostimulation pulses polarity, data generated by the electrostimulating applicators, preferably the user's skin resistance value or battery charge level.

7. The method, according to claims 4, 5, or 6, characterized in that the data introduced by the user to PC or mobile device (AM) include: biometric data of the user, preferably gender, age, weight, height, BMI, data on the user's health, preferably data about current and past illnesses, medications taken, perceived discomfort, duration of symptoms, data on the location of applicators, assessment of the user's perceived pain or other ailments, preferably on VAS scale or other, assessment of the user's perceived comfort or discomfort related to the current parameters of electrostimulation.

8. The method, according to claims 5, 6, or 7, characterized in that the raw data taken from the accelerometers in the mobile device (AM) include: data on the user's current activity, preferably on motion, number of steps taken, number of floors climbed.

9. The method, according to claims 5, 6, 7, or 8, characterized in that the data generated by a smartwatch or smart band connected with the mobile device include data: on the user's current heart rate and activity, preferably on motion, number of steps taken, number of floors climbed.

10. The method, according to claims 5, 6, 7, 8 or 9, characterized in that the recommended operating parameters of the electrostimulating applicator include: cycles duration (Cl, C2), stimulation pulses current intensity (CC1, CC2), pulses width (BC1, BC2), pulses repetition frequency (AC1, AC2), stimulation duration (PI), pause time between stimulations (P2).

11. The method, according to claims 5, 6, 7, 8, 9 or 10, characterized in that the recommended operating parameters (RPP) are subject to modification by a user (MPE).

12. A system for transdermal electrostimulation comprising at least one electrostimulating applicator (AE), as defined in claim 1, wherein the operation of the electrostimulating applicator (AE) is controlled by the method according to claim 5.

13. The system, according to claim 12, characterized in that it comprises at least two electrostimulating applicators (A), as defined in claim 1, wherein the electrostimulating applicators (AE) are controlled independently of each other.

14. The system, according to claim 12 or 13, characterized in that the electrostimulating applicators (AE) are operating independently of each other, wherein the applicators form at least one group of electrostimulating applicators (AE), wherein the group comprises no more than four electrostimulating applicators.

15. The system, according to claims 12 to 14, characterized in that it comprises at least two groups of electrostimulating applicators (AE), the groups being controlled independently.

16. A use of the system according to claim 12 in the pain treatment.

17. The use, according to claim 16, in the treatment of post-operative pain in patients after inguinal hernia surgery.

18. The use, according to claim 16, in the treatment of perinatal pain.