Wearable epilepsy diagnosis and treatment integrated device and use method thereof

Abstract

The invention discloses a wearable epilepsy diagnosis and treatment integrated device and a use method thereof, and belongs to the technical field of epilepsy detection and treatment, the device comprises an electroencephalogram acquisition module, an electroencephalogram detection module and an electric controlled drug release module, the electroencephalogram acquisition module is connected with the electroencephalogram detection module, and the electroencephalogram detection module is connected with the electric controlled drug release module. According to the wearable epilepsy diagnosis and treatment integrated device and the use method thereof, the problem of random epilepsy seizure in home care of epileptics is solved, the epileptics are helped to reduce the dosage of psychotropic drugs so as to reduce toxic and side effects, the number of medical treatment times of the epileptics is reduced, and the autonomous living ability of the epileptics is improved; the life quality of epilepsy patients is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of epilepsy detection and treatment, and particularly relates to a wearable integrated epilepsy diagnosis and treatment device and a using method thereof. Background Art

[0002] Epilepsy is a chronic neurological disease that affects people of all ages, characterized by recurrent epileptic seizures caused by abnormal discharges of brain neurons. During an epileptic seizure, a part of the body or the whole body has a brief involuntary convulsion, sometimes accompanied by loss of consciousness and urinary and fecal incontinence.

[0003] In the treatment of epilepsy, patients can take anti-epileptic drugs for treatment. However, there are still some patients who have poor treatment effects with anti-epileptic drugs, and long-term use of psychiatric drugs will bring strong toxic and side effects. Epileptic seizures are unpredictable. Frequent seizures or occasional grand mal seizures seriously affect the quality of life of epilepsy patients. If there is no external help during an attack, it may endanger the patient's life safety. If epilepsy can be predicted before an attack and drugs can be administered in time for intervention, the probability of epileptic seizures can be greatly reduced, and the harm caused by epileptic seizures to the body can be reduced. Nowadays, the gold standard for diagnosing epilepsy is electroencephalogram (EEG). However, EEG needs to be observed using hospital equipment. The commonly used scalp electrodes are silver chloride wet electrodes, which require conductive paste or conductive gel to be applied to the scalp, causing strong discomfort, and cannot support real-time long-term observation, which is very inconvenient for epilepsy patients.

[0004] In terms of drug delivery, traditional oral administration and transdermal administration have disadvantages such as low efficiency, slow speed, and limited drug selection. Summary of the Invention

[0005] The purpose of the present invention is to provide a wearable integrated epilepsy diagnosis and treatment device and a using method thereof, to solve the problem of random epileptic seizures encountered in the home care of epilepsy patients, help epilepsy patients reduce the dosage of psychiatric drugs and thus reduce toxic and side effects, reduce the number of hospital visits of patients and improve their self-care ability, and improve the quality of life of epilepsy patients.

[0006] To achieve the above purpose, the present invention provides a wearable integrated epilepsy diagnosis and treatment device, including an electroencephalogram (EEG) acquisition module, an EEG detection module, and an electronically controlled drug release module. The EEG acquisition module is connected to the EEG detection module, and the EEG detection module is connected to the electronically controlled drug release module; The EEG acquisition module includes an amplifier, a filter, an analog-to-digital converter, electrodes, and a battery. Among them, the amplifier is electrically connected to the electrodes and the filter respectively, the filter is electrically connected to the analog-to-digital converter, and the battery is electrically connected to the amplifier, the filter, the analog-to-digital converter, and the electrodes.

[0007] Preferably, the electroencephalogram detection module includes a microcontroller, Bluetooth, and a mobile phone. The microcontroller is electrically connected to the analog-to-digital converter and Bluetooth respectively, and Bluetooth is electrically connected to the mobile phone.

[0008] Preferably, the electronically controlled drug release module includes electronically controlled microneedles and a digital-to-analog converter. The digital-to-analog converter is electrically connected to the microcontroller and the electronically controlled microneedles respectively.

[0009] The usage method of the above-mentioned wearable epilepsy diagnosis and treatment integrated device includes the following steps: Step 1: Use electrodes to collect scalp electroencephalogram signals, and perform preprocessing through an amplifier, a filter, an analog-to-digital converter, and a digital signal processor. Step 2: Transmit the data to the microcontroller. The microcontroller analyzes the preprocessed electroencephalogram data, and sends the epilepsy detection result to the mobile phone for visual display. Step 3: The microcontroller converts the drug release signal into a voltage through the digital-to-analog converter, and stimulates the electronically controlled microneedles to release the drug.

[0010] Preferably, in Step 1, the electrodes are composed of silver-silver chloride dry electrodes. The electrodes are attached to the human scalp through a headband. The amplification factor of the amplifier is 20 - 40 dB, and the accuracy of the analog-to-digital converter is 16 bits.

[0011] Preferably, in Step 2, the time-frequency domain analysis method is used to analyze the electroencephalogram data. The specific operation is as follows: First, select a 1s signal for wavelet transform, select the Haar wavelet basis, convert the time-domain signal to the time-frequency domain, and analyze its time-frequency diagram in the time-frequency domain. During a period of time before epilepsy and during epileptic seizures, the power of the high-frequency part of the electroencephalogram signal will increase significantly. Judge the seizure situation of epilepsy through this information. Pack the seizure situation into 8 bytes. The first four bytes are data identifiers, the fifth and sixth bytes are voltage data, and the seventh and eighth bytes are check bits. Send the result and the preprocessed electroencephalogram signal to the computer through Bluetooth. The computer uses the pyserial module and the pyqtgraph module in the python language, and specifically uses the Multiprocessing multi-process module to realize data reception and visualization. The visualization has two parts, one is the real-time visualization of the electroencephalogram signal, and the other is the alarm reminder visualization of the epileptic seizure state.

[0012] Preferably, in Step 2, analyze whether the signal is a pre-signal of epileptic seizure. If it is not a pre-signal of epileptic seizure, return to the start stage. If it is a pre-signal of epileptic seizure, enter Step 3.

[0013] Preferably, in Step 3, judge whether it lasts for 1 minute. If it does not need to last for 1 minute, return to the start stage. If it needs to last for 1 minute, then voltage excitation releases the drug. After that, it is determined whether the epilepsy has ended. If it has ended, the system returns to the starting stage. If it has not ended, voltage excitation continues to release the drug.

[0014] The present invention combines epilepsy signal detection with drug delivery. Using an electro-controlled microneedle as a carrier and technologies such as micro-device processing, physiological signal detection, and drug control, an integrated diagnosis and treatment intelligent drug delivery system is developed. The system acquires electroencephalogram (EEG) signals through electrodes and is connected to a data transmission, signal processing, and control module. After detecting an epileptic seizure using an intelligent recognition algorithm, drugs are released as needed through the electro-controlled microneedle in a voltage-controlled manner. After detecting the end of epilepsy or the return of the EEG signal to normal, drug administration stops, thereby realizing dynamic monitoring and integrated diagnosis and treatment of epilepsy patients.

[0015] Therefore, the present invention adopts the above-mentioned wearable integrated epilepsy diagnosis and treatment device and its usage method, which has the following beneficial effects: (1) Solve the problem of random epileptic seizures encountered in the home care of epilepsy patients, help epilepsy patients reduce the dosage of psychotropic drugs, thereby reducing side effects, reduce the number of hospital visits of patients, and improve their self-care ability, and improve the quality of life of epilepsy patients; (2) Can real-time monitor the epileptic seizure state of epilepsy patients and administer drugs as needed, which can avoid grand mal seizures or alleviate the symptoms of grand mal seizures; (3) The device is designed as a wearable headband, which is small, flexible, and convenient for patients to use at home; (4) The EEG acquisition technology is mature, and the electro-controlled microneedle drug delivery technology is inexpensive, with a low overall cost; (5) The electro-controlled microneedle can be replaced after the drug is used up, the device has a long service life, and the usage cost is further reduced.

[0016] Next, through the drawings and embodiments, the technical solutions of the present invention will be further described in detail. Description of the Drawings

[0017] Figure 1 is a schematic structural diagram of an embodiment of a wearable integrated epilepsy diagnosis and treatment device and its usage method of the present invention; Figure 2 is a flowchart of an embodiment of a wearable integrated epilepsy diagnosis and treatment device and its usage method of the present invention; Figure 3 is a drug release test of phenytoin sodium at different voltages in an embodiment of a wearable integrated epilepsy diagnosis and treatment device and its usage method of the present invention; Figure 4 is a surface-gilded polylactic acid microneedle in an embodiment of a wearable integrated epilepsy diagnosis and treatment device and its usage method of the present invention; Figure 5It is the polylactic acid microneedle after surface polymerization of pyrrole in an embodiment of a wearable integrated epilepsy diagnosis and treatment device and its usage method of the present invention. Detailed implementation manners

[0018] The technical solutions of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0019] Unless otherwise defined, the technical terms or scientific terms used in the present invention should have the ordinary meanings understood by those of ordinary skill in the field to which the present invention belongs. The "first", "second" and similar terms used in the present invention do not indicate any order, quantity or importance, but are only used to distinguish different components. The terms such as "including" or "comprising" mean that the elements or objects appearing before this word cover the elements or objects listed after this word and their equivalents, without excluding other elements or objects. The terms such as "connected" or "coupled" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. The terms such as "upper", "lower", "left", "right" are only used to represent relative position relationships, and when the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0020] Embodiment 1 As Figure 1 shown, the present invention provides a wearable integrated epilepsy diagnosis and treatment device, including an electroencephalogram (EEG) acquisition module, an EEG detection module and an electrically controlled drug release module. The EEG acquisition module is connected to the EEG detection module, and the EEG detection module is connected to the electrically controlled drug release module.

[0021] Among them, the EEG acquisition module is used to acquire scalp EEG signals and then transmit the scalp EEG signals to the EEG detection module. The EEG detection module is used to analyze the scalp EEG signals and then transmit the analysis results to the electrically controlled drug release module. The electrically controlled drug release module is used for alkenyl electrically controlled microneedles to release drugs, so as to control the patient's condition.

[0022] The EEG acquisition module includes an amplifier, a filter, an analog-to-digital converter, electrodes and a battery. Among them, the amplifier is electrically connected to the electrodes and the filter respectively, the filter is electrically connected to the analog-to-digital converter, and the battery is electrically connected to the amplifier, the filter, the analog-to-digital converter and the electrodes.

[0023] Among them, the electrode is in close contact with the human scalp and is used to collect scalp electroencephalogram (EEG) signals. The specific arrangement of the electrodes refers to the international 10-20 system; the signal amplifier is used to amplify the EEG signals as low as dozens of microvolts, and the amplification factor is 30 dB; the filter is used to filter out the 50 Hz power frequency interference and the background noise generated by movement, etc.; the analog-to-digital converter is used to convert the collected EEG signals into digital signals, and the conversion accuracy is 16 bits. The EEG acquisition module also includes a digital signal processor, which is used to package the EEG signals and transmit the original data externally; the battery is used to supply power to the above devices, and a button battery can be used, and the battery life is about 7 days.

[0024] The EEG detection module includes a microcontroller, Bluetooth, and a mobile phone. The microcontroller is electrically connected to the analog-to-digital converter and Bluetooth respectively, and Bluetooth is electrically connected to the mobile phone. Among them, the microcontroller is used to perform algorithm analysis on the computer signals transmitted by the digital signal processor, including wavelet transform, power spectral density analysis, etc. In the wavelet transform, Haar wavelet basis is used. In the power spectral density analysis, the detection threshold is determined according to the power value of the normal signal, and the set drug release signal is output; Bluetooth sends the detection result of the microcontroller to the mobile phone for early warning; the mobile phone will visually display the epilepsy seizure situation to prompt the patient.

[0025] The electrically controlled drug release module includes an electrically controlled microneedle and a digital-to-analog converter. The digital-to-analog converter is electrically connected to the microcontroller and the electrically controlled microneedle respectively. Among them, the digital-to-analog converter is used to convert the drug release signal output by the microcontroller into a voltage analog signal; the electrically controlled microneedle is used to release the drug.

[0026] As Figure 4 、 Figure 5 shown, the electrically controlled microneedle is prepared by the inverse molding method with polylactic acid material. A male mold is printed using high-precision 3D printing technology, and the material is photosensitive resin. A female mold is made using polydimethylsilane. The method is to pour polydimethylsiloxane into the microneedle male mold and bake it at 60 °C for 20 minutes. After the polydimethylsilane is cured, it serves as the microneedle female mold; then the polylactic acid microneedles are prepared by the high-temperature melting method. The method is to place polylactic acid particles on the surface of the female mold. At a high temperature of 230 °C, the polylactic acid melts, vacuum is extracted and cooled to form polylactic acid microneedles; a gold conductive layer is sputtered on the surface of the microneedles by an ion sputtering instrument to make it conductive. The sputtering pressure is 10 mbar, the current is 15 mA, and the sputtering time is 12 minutes. Then, pyrrole doped with antiepileptic drugs sodium valproate, phenytoin sodium, and carbamazepine is polymerized on the surface of the electrically controlled microneedles through an electrochemical reaction. The specific area of the electrically controlled microneedle is 225 mm 2 , and there is a 15×15 microneedle array on the surface. The length of each needle is 800 μm, conical, and the bottom diameter is 300 μm.

[0027] The drug release test of phenytoin sodium is as Figure 3As shown in the figure, it can be seen from the figure that phenytoin sodium can control the drug release rate by changing the voltage, and the drug release effect is significant and stable. The main principle is that the drug-releasing microneedle serves as the anode, and pyrrole undergoes an oxidation reaction at the anode to form a dense polypyrrole film. The polypyrrole is doped with an anti-epileptic drug. The specific manufacturing method is to dissolve pyrrole and the anti-epileptic drug in water at a certain concentration, insert the anode and cathode into the solution, and carry out an electrochemical reaction. When releasing the drug, the microneedle electrode serves as the cathode, a reduction reaction occurs, the polypyrrole loses its charge, and the drug is released.

[0028] Polypyrrole is a common conductive polymer. Pyrrole monomers can undergo an oxidation reaction to form polypyrrole, and polypyrrole can encapsulate negatively charged drugs. Anti-epileptic drugs such as sodium valproate and phenytoin sodium are the preferred drugs. In the electrochemical reaction cell, the polylactic acid microneedle is used as the anode, and pyrrole will polymerize on the surface of the microneedle to form a polypyrrole film, and the anti-epileptic drug is encapsulated in the film. When releasing the drug, under the voltage stimulation, a reduction reaction occurs at the electrode where the polypyrrole is located, and the drug is released. Using sodium fluorescein as a model drug, when the drug is released, there is an obvious corresponding relationship between the energization time and the drug release amount. The characterization method of sodium fluorescein is to measure the absorbance with an enzyme-labeling instrument at 496 nm. The characterization method of drugs such as sodium valproate is high-performance liquid chromatography (HPLC). The chromatographic conditions are that the mobile phase is set as methanol-water (80, 20), the flow rate is 0.9 mL / min, the detection wavelength is 265 nm, the column temperature is 30 °C, and the injection volume is 20 μL. In this embodiment, simulated epileptic EEG signals are used, and the data comes from Boston Children's Hospital (CHB-MIT Scalp EEG Database). The headband is worn closely to the head to minimize the occlusion of hair as much as possible. When the epileptic signal is about to occur, the device will alarm and initiate voltage excitation, and the drug loaded on the microneedle is released. When the pre-epileptic seizure signal ends, the voltage excitation is stopped, and the microneedle immediately stops releasing the drug. The amount of sodium fluorescein released is quantitatively measured using an enzyme-labeling instrument.

[0029] The whole set of devices is integrated into an integrated headband and worn on the forehead. When a pre-epileptic seizure signal is detected, voltage excitation is initiated, and the drug is released. After the pre-epileptic seizure signal disappears, the voltage excitation is stopped, realizing closed-loop drug delivery.

[0030] As Figure 2 shown, the usage method of the above-mentioned wearable integrated epilepsy diagnosis and treatment device includes the following steps: Step 1: Use electrodes to collect scalp EEG signals and perform preprocessing through an amplifier, filter, analog-to-digital converter, and digital signal processor. The electrodes are composed of silver-silver chloride dry electrodes. The electrodes are attached to the human scalp through a headband. The amplification factor of the amplifier is 20 - 40 dB, and the accuracy of the analog-to-digital converter is 16 bits.

[0031] Step 2: Transmit the data to the microcontroller. The microcontroller analyzes the preprocessed EEG data and sends the epilepsy detection result to the mobile phone for visual display.

[0032] Analyze the EEG data using the time-frequency domain analysis method. The specific operation is as follows: First, select a 1s signal for wavelet transform, use the Haar wavelet basis to convert the time-domain signal to the time-frequency domain, and analyze its time-frequency diagram in the time-frequency domain. During a period before epilepsy and during an epileptic seizure, the power of the high-frequency part of the EEG signal will increase significantly. Judge the occurrence of epilepsy based on this information. Pack the seizure situation into 8 bytes. The first four bytes are data identifiers, the fifth and sixth bytes are voltage data, and the seventh and eighth bytes are check bits. Send the result and the preprocessed original EEG signal to the computer via Bluetooth. The computer uses the pyserial module and the pyqtgraph module in the Python language, and specifically uses the Multiprocessing multi-process module to implement data reception and visualization. The visualization has two parts, one is the real-time visualization of the EEG signal, and the other is the alarm reminder visualization of the epileptic seizure state.

[0033] Analyze whether the signal is a pre-signal of an epileptic seizure. If it is not a pre-signal of an epileptic seizure, return to the start stage. If it is a pre-signal of an epileptic seizure, enter Step 3.

[0034] Step 3: The microcontroller converts the drug release signal into a voltage through a digital-to-analog converter and stimulates the electro-controlled microneedles to release the drug.

[0035] Judge whether it lasts for 1 minute. If it does not need to last for 1 minute, return to the start stage. If it needs to last for 1 minute, then the voltage stimulates the release of the drug.

[0036] Then judge whether the epilepsy has ended. If it has ended, return to the start stage. If it has not ended, continue to stimulate the release of the drug with voltage. Continuously administer the drug before the end of the epileptic seizure pre-signal and stop administering the drug after the epileptic seizure pre-signal disappears, realizing closed-loop control of drug release.

[0037] Therefore, the present invention adopts the above-mentioned wearable integrated epilepsy diagnosis and treatment device and its usage method to solve the problem of random epileptic seizures encountered in the home care of epilepsy patients, help epilepsy patients reduce the dosage of psychiatric drugs and thus reduce the toxic and side effects, reduce the number of hospital visits of patients and improve their self-care ability, and improve the quality of life of epilepsy patients.

[0038] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions of the present invention or make equivalent replacements, and these modifications or equivalent replacements do not enable the modified technical solutions to depart from the spirit and scope of the technical solutions of the present invention.

Claims

1. A wearable integrated epilepsy diagnosis and treatment device, characterized in that: It includes an EEG acquisition module, an EEG detection module and an electric controlled drug release module, wherein the EEG acquisition module is connected to the EEG detection module, and the EEG detection module is connected to the electric controlled drug release module; The EEG acquisition module includes an amplifier, a filter, an analog-to-digital converter, electrodes and a battery, wherein the amplifier is electrically connected to the electrode and the filter respectively, the filter is electrically connected to the analog-to-digital converter, and the battery is electrically connected to the amplifier, the filter, the analog-to-digital converter and the electrodes.

2. A wearable integrated epilepsy diagnosis and treatment device according to claim 1, characterized in that: The electroencephalogram detection module includes a microcontroller, Bluetooth and a mobile phone. The microcontroller is electrically connected to the analog-to-digital converter and the Bluetooth respectively, and the Bluetooth is electrically connected to the mobile phone.

3. A wearable epilepsy diagnosis and treatment integrated device according to claim 1, characterized in that: The electrically controlled drug release module comprises an electrically controlled microneedle and a digital-to-analog converter, and the digital-to-analog converter is electrically connected to the microcontroller and the electrically controlled microneedle respectively.

4. A method for using a wearable integrated epilepsy diagnosis and treatment device as claimed in any one of claims 1 to 3, characterized in that: The following steps are involved: Step 1: Use electrodes to collect scalp EEG signals and pre-process them through amplifiers, filters, analog-to-digital converters and digital signal processors; Step 2: Data is transmitted to the microcontroller, which analyzes the pre-processed EEG data and sends the epilepsy detection results to the mobile phone for visual display; Step 3: The microcontroller converts the drug release signal into voltage through a digital-to-analog converter, stimulating the electrically controlled microneedle to release the drug.

5. The method for using a wearable integrated epilepsy diagnosis and treatment device according to claim 4, characterized in that: In step 1, the electrode is composed of a silver-silver chloride dry electrode, the electrode is attached to the human scalp through a headband, the amplifier gain is 20-40dB, and the analog-to-digital converter accuracy is 16 bits.

6. The method for using a wearable integrated epilepsy diagnosis and treatment device according to claim 4, characterized in that: In step 2, the EEG data is analyzed by using the time-frequency domain analysis method. The specific operations are as follows: first, the 1s model is selected for wavelet transform, and the Haar wavelet basis is selected to convert the time domain signal to the time-frequency domain. The time-frequency diagram is analyzed in the time-frequency domain. The power of the high-frequency part of the EEG signal will increase significantly in the period before epilepsy and during epileptic seizures. This information is used to judge the onset of epilepsy. The seizure situation is packaged into 8 bytes, the first four bytes are data identifiers, the fifth and sixth bytes are voltage data, and the seventh and eighth bytes are check bits. The results and preprocessed EEG signals are sent to the computer via Bluetooth. The computer uses the pyserial module and pyqtgraph module in the python language, and specifically uses the Multiprocessing multi-process module to achieve data reception and visualization. The visualization has two parts, one is the real-time visualization of EEG signals, and the other is the alarm reminder visualization of the epileptic seizure status.

7. The method for using a wearable integrated epilepsy diagnosis and treatment device according to claim 4, characterized in that: In step 2, the signal is analyzed to determine whether it is a pre-epilepsy seizure signal. If it is not a pre-epilepsy seizure signal, the process returns to the beginning. If it is a pre-epilepsy seizure signal, the process proceeds to step 3.

8. The method for using a wearable integrated epilepsy diagnosis and treatment device according to claim 4, characterized in that: In step 3, it is determined whether it lasts for 1 minute. If it does not need to last for 1 minute, it returns to the beginning stage. If it needs to last for 1 minute, the voltage is stimulated to release the drug. Then determine whether the epilepsy has ended. If it has ended, return to the starting stage. If it has not ended, continue voltage stimulation to release drugs.

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