A closed-loop vagus nerve stimulation system for depression

Abstract

The present invention proposes a closed-loop vagus nerve stimulation system for depression, wherein an implantable nanogenerator collects heartbeat mechanical energy and converts it into electrical energy; a power management module collects and stores the electrical energy converted by the implantable nanogenerator; a heart rate sensor collects heart rate data and transmits it to a feedback microcontroller; the feedback microcontroller receives and identifies abnormal heart rate data generated before or during the onset of depression, triggers a control switch between the power management module and the pulse generator, and the pulse generator outputs the energy stored in the power management module to the vagus nerve stimulation electrode in the form of an electrical pulse; the vagus nerve stimulation electrode electrically stimulates the vagus nerve. The present invention breaks through the technical bottleneck that the existing vagus nerve stimulation technique cannot be stably applied in clinical practice for a long time. On the basis of retaining the advantages of traditional vagus nerve stimulation such as minimally invasive surgery and precise stimulation, a self-powered unit is introduced, and the entire system is directly driven by the heartbeat, which can achieve long-term stable self-driven closed-loop vagus nerve stimulation.

Description

Technical Field

[0001] The present invention belongs to the field of medical equipment, and in particular relates to a self-driven closed-loop vagus nerve stimulation system for depression. Background Art

[0002] Vagus nerve stimulation (VNS) is a new method used in the treatment of drug-resistant epilepsy in the past 20 years. It is a neuromodulation technology that treats drug-resistant epilepsy by stimulating one side of the cervical vagus nerve. Because the parasympathetic fibers of the left vagus nerve are mainly distributed in the atrium, and the parasympathetic fibers of the right vagus nerve are mainly distributed in the ventricle, VNS generally chooses the left vagus nerve to reduce the occurrence of adverse cardiac reactions. The operation is performed under general anesthesia, without the need for craniotomy. Only a small incision is made in the neck and chest. The stimulating electrode is wrapped and fixed on the left vagus nerve trunk (below the upper and lower branches of the cervical cardiac branch), the pulse generator is implanted in the left chest, and the wire and the pulse generator are connected. The vagus nerve stimulator is usually turned on after 2 weeks to adjust the stimulation parameters. The existing VNS stimulator consists of a pulse generator, a wire (including 2 spiral electrodes and a fixed loop anchor), an in vitro parameter program controller, and an in vitro magnet.

[0003] VNS surgery has been widely used due to its advantages such as "no need for craniotomy, less surgical damage, fewer surgical complications, faster postoperative recovery, definite efficacy, and adjustable surgical effect". The principles of VNS in treating refractory depression are as follows: 1. The electrical stimulation signals transmitted by VNS pass through the solitary nucleus and directly act on the cerebellum, hypothalamus, thalamus, amygdala, limbic system and cerebral cortex. 2. The ascending fibers of the vagus nerve are indirectly projected to the locus coeruleus through the solitary nucleus. Therefore, stimulating the vagus nerve can enhance the functional activity of the locus coeruleus, thereby increasing the concentration of norepinephrine.

[0004] Closed-loop neurostimulation systems can adjust the treatment state according to physiological changes, that is, stimulation is selectively triggered through the patient's own physiological activities only when a pathological state is detected. Compared with open-loop therapy, closed-loop neuromodulation can control the stimulation time, enhance the clinical stimulation effect and reduce the risk of neurological discomfort. Studies over the past 50 years have shown that there is an association between depression and abnormal autonomic nervous system (ANS) activity. Significantly increased heart rate (HR) and low levels of heart rate variation (HRV) have been shown to be markers of ANS state. Cardiac parameters can serve as potential, non-invasive markers of depressive state. Early studies have shown that the diagnosis of depression, possibly combined with anxiety, is associated with higher HR and lower HRV in the overall 24-hour recording, and that the HR of patients with depression remains elevated during sleep. Schiweck et al. found that patients with depression had a higher baseline heart rate, with an average heart rate of 10-15 beats / min higher than that of the control group. The heart rate of patients with depression after treatment was close to that of the control group. Therefore, it is feasible to build a closed-loop neurostimulation system that can identify abnormal heart rate events and trigger electrical stimulation.

[0005] Although VNS has been proven to be effective in treating depression, there are still some problems in actual clinical applications that limit the promotion and popularization of VNS. First, vagus nerve stimulation devices are expensive and cannot be implanted in the body for a long time due to limited battery energy supply. Depression requires long-term treatment. A second operation to replace the vagus nerve stimulator will not only increase the risk of exogenous infection, but also bring a heavy economic burden to patients. Secondly, the existing VNS in the treatment of depression has inconsistent final clinical trial results due to heterogeneity of responses between individuals, which hinders the large-scale clinical application of VNS. In addition, the current VNS stimulation intensity mostly depends on the subjective consciousness of the patient or doctor, and patient compliance is poor. In view of the problems and shortcomings of VNS, it is urgent to develop new neuroregulatory technologies to achieve safer, more reliable and long-term stable closed-loop pulse electrical stimulation of the vagus nerve while retaining the advantages of minimally invasive surgery and precise stimulation of traditional vagus nerve stimulation.

[0006] Therefore, there is an urgent need to solve the problem of self-driving and self-regulation of the vagus nerve stimulation system. Summary of the invention

[0007] In order to overcome the problems of the prior art, the present invention provides a vagus nerve stimulation system for depression, introduces a self-powered (self-driven) unit, establishes a new "monitoring-feedback-treatment" closed-loop neural regulation mode, and broadens the clinical application of vagus nerve stimulation.

[0008] The present invention provides the following technical solutions:

[0009] A closed-loop vagus nerve stimulation system for depression includes an implantable nanogenerator, a power management module, a heart rate sensor, a feedback microcontroller, a pulse generator and a vagus nerve stimulation electrode. The implantable nanogenerator collects the mechanical energy of heartbeat and converts it into electrical energy; the power management module collects and stores the electrical energy converted by the implantable nanogenerator to achieve AC / DC energy conversion and energy storage; the heart rate sensor collects heart rate data and transmits it to the feedback microcontroller; the feedback microcontroller receives and processes the heart rate data, identifies abnormal heart rate data generated before or during the onset of depression, triggers the pulse generator to output electrical pulses to the vagus nerve stimulation electrode, and the vagus nerve stimulation electrode stimulates the vagus nerve.

[0010] Furthermore, the implantable nanogenerator is a piezoelectric-friction composite nanogenerator, which is placed between the heart and the pericardium, and comprises, from the inside to the outside, a first electrode layer, a first friction layer, a piezoelectric layer, a second electrode layer, a third electrode layer, a first packaging layer, and a second packaging layer, respectively. The first friction layer is a polymer friction layer and the inner surface is provided with a micro-nano structure. An air layer is formed between the first friction layer and the inner surface of the first electrode layer. The inside and outside of the piezoelectric layer are respectively bonded to the first electrode layer and the third electrode layer. The other side of the first friction layer is in contact with the second electrode layer. The outermost layer is packaged by the first packaging layer and the second packaging layer in turn, and one side of the second electrode layer faces the anterior wall of the left ventricle.

[0011] Furthermore, the heart rate sensor is a friction nanogenerator, which comprises, from the inside to the outside, a second friction layer, a fourth electrode layer / a third friction layer, a fifth electrode layer, a first substrate layer, and a third packaging layer which are arranged opposite to each other; the second friction layer is a polymer friction layer and a micro-nano structure is provided on the inner surface; an air layer is formed between the second friction layer and the inner surface of the fourth electrode layer / the third friction layer; the fifth electrode layer is adhered to the outer side of the second friction layer; the fourth electrode layer / the third friction layer is adhered to the outer side of the first substrate layer; the outermost layer is provided with a packaging layer; the heart rate sensor is fixed on the outer surface of the heart to generate electrical pulses whose frequency is consistent with the heart rate and whose intensity depends on the strength of the heartbeat.

[0012] Furthermore, the power management module includes a rectifying and filtering unit and an energy storage unit. The power management module is connected to the implantable nanogenerator. The rectifying and filtering unit completes AC / DC energy conversion. The energy storage unit stores electrical energy. The power management module is implanted subcutaneously.

[0013] Furthermore, the feedback microcontroller includes a signal receiving unit, a microprocessor and a control switch. The signal receiving unit of the feedback microcontroller transmits the received heart rate sensor electrical signal to the microprocessor, and pre-sets the abnormal heart rate threshold and abnormal heart rate range before or during the onset of depression for the microprocessor. The microprocessor compares the received heart rate signal with the preset abnormal heart rate characteristic value before or during the onset of depression. When it is higher than the highest threshold of the abnormal heart rate or lower than the lowest threshold of the abnormal heart rate, the control switch on the feedback microcontroller is turned on, and the power management module forms a path with the pulse generator to trigger the pulse generator.

[0014] Furthermore, the pulse generator outputs a pulse frequency of 1-145 Hz and a voltage of 0-12.0 V.

[0015] Furthermore, the vagus nerve stimulation electrode and the pulse generator are connected by a nerve stimulation wire, and the vagus nerve stimulation electrode is spiral-shaped and wound around the vagus nerve.

[0016] Furthermore, the base layer of the vagus nerve stimulation electrode is a wire base, the wire base is a degradable polymer wire, a conductive layer is provided on the outside of the base layer, the conductive layer is a degradable metal, the encapsulation layer covers the conductive layer, and both ends are exposed, the encapsulation layer is a degradable polymer, and the wires exposed at both ends are respectively connected to the pulse generator and the vagus nerve target position.

[0017] A method for triggering a pulse generator by a microprocessor: setting a start threshold on the microprocessor, comparing the start threshold with the patient's current heart rate data, and calculating the heart rate change rate R hr , R hr When the positive and negative difference is greater than 20%, the pulse generator is started to output a stimulation signal;

[0018] R hr =[(V m -V bg )-(V0-V bg )] / V0, where V m V is the average value of the sensor output intensity at the maximum or minimum heart rate per unit time. bg It is the average value of the sensor output intensity at the background heart rate per unit time, and V0 is the average value of the sensor output intensity at the normal heart rate per unit time.

[0019] By adopting the above technical solution, the present invention has the following beneficial effects:

[0020] (1) The present invention overcomes the technical bottleneck that the existing vagus nerve stimulation cannot be applied in clinical practice in a long-term and stable manner. While retaining the advantages of traditional vagus nerve stimulation such as minimally invasive surgery and precise stimulation, it introduces a self-powered (self-driven) unit. The entire system is directly driven by the heartbeat, which can achieve long-term and stable self-powered vagus nerve stimulation.

[0021] (2) The present invention establishes a new "monitoring-feedback-treatment" closed-loop neural regulation mode. After the abnormal heart rate signal related to depression is accurately identified by the self-driven sensor, the switch of the trigger feedback microcontroller is turned on, and the pulse generator can provide pulse electrical stimulation to the vagus nerve. The establishment of this mode is another exploration of vagus nerve stimulation in the field of neuroscience, which can broaden the clinical application of vagus nerve stimulation and provide theoretical support for the development of new neural regulation technologies and methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a schematic diagram of the structure of the closed-loop vagus nerve stimulation system for depression according to the present invention;

[0023] Figure 2 This is the working principle diagram of the heart rate sensor, feedback microcontroller and pulse generator;

[0024] Figure 3 is a schematic diagram of the structure of an implantable nanogenerator;

[0025] Figure 4 is a structural diagram of a heart rate sensor;

[0026] Figure 5 This is the experimental result graph of the heart rate sensor output performance;

[0027] Figure 6 Schematic diagram of the structure of the vagus nerve stimulation electrode.

[0028] Description of Reference Numerals

[0029] 1 first electrode layer, 2 first friction layer, 3 piezoelectric layer, 4 second electrode layer, 5 third electrode layer, 6 first packaging layer, 7 second packaging layer, 8 second friction layer, 9 fourth electrode layer / third friction layer, 10 fifth electrode layer, 11 first substrate layer, 12 third packaging layer, 13 wire, 14 second substrate layer, 15 conductive layer, 16 fourth packaging layer. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the structural diagrams and specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0031] Example 1

[0032] The present invention provides a closed-loop vagus nerve stimulation system for depression, such as Figure 1As shown, it includes an implantable nanogenerator, a power management module, a heart rate sensor, a feedback microcontroller, a pulse generator and a vagus nerve stimulation electrode. The heart rate sensor, the feedback microcontroller and the pulse generator together form a self-feedback module. The implantable nanogenerator collects the mechanical energy of the heartbeat and converts it into electrical energy; the power management module collects and stores the electrical energy converted by the implantable nanogenerator to achieve AC / DC energy conversion and energy storage; the heart rate sensor collects heart rate data and transmits it to the feedback microcontroller; the feedback microcontroller receives and processes the heart rate data, identifies abnormal heart rate data generated before or during the onset of depression, identifies abnormal heart rate data generated before or during the onset of depression, and triggers the pulse generator to output electrical pulses to the vagus nerve stimulation electrode, which stimulates the vagus nerve. The system is directly powered by the heartbeat movement of the organism, and the electrical stimulation acts on the vagus nerve.

[0033] Electrical stimulation acts on the vagus nerve in the form of electric current, which can not only enhance noradrenergic and serotonergic neurotransmission in brain areas (e.g., prefrontal cortex, amygdala and hippocampus) that are critical for emotion regulation, but also may enhance neuroplasticity. Ultimately, the purpose of promoting the regulation of vagus nerve to treat depression is achieved. The closed-loop vagus nerve stimulation system developed by the present invention can monitor the patient's heart rate state in real time and perform self-regulated vagus nerve stimulation. The stimulation system is flexible, light, simple, and the stimulation parameters have the advantage of low levels. It should be understood that the present invention can also be used to treat other nervous system diseases (Parkinson's, epilepsy) and arrhythmia.

[0034] like Figure 3 As shown, the implantable nanogenerator is a piezoelectric-friction composite nanogenerator, which is placed between the heart and the pericardium. The piezoelectric-friction composite nanogenerator is composed of the first electrode layer 1, the first friction layer 2, the piezoelectric layer 3, the second electrode layer 4, the third electrode layer 5, the first packaging layer 6, and the second packaging layer 7, which are arranged oppositely from the inside to the outside. The first electrode layer 1 serves as both an electrode layer and a friction layer. The first friction layer 2 is a polymer friction layer and has a micro-nano structure on its inner surface. An air layer is formed between the first friction layer 2 and the inner surface of the first electrode layer 1. The piezoelectric layer 3 is respectively attached to the first electrode layer 1 and the third electrode layer 5 on the inside and outside. The other side of the first friction layer 2 is in contact with the second electrode layer 4. The outermost layer is packaged by the first packaging layer 6 and the second packaging layer 7 in turn. One end of the wire 13 is connected to the second electrode layer 4 and the third electrode layer 5 respectively, and the other end is connected to the power management module. One side of the second electrode layer faces the anterior wall of the left ventricle.

[0035] The working principle of the piezoelectric-friction composite nanogenerator is the coupling of friction electrification effect, electrostatic induction effect and piezoelectric effect. The device generates output externally as the heart beats. When the device is subjected to heartbeat pressure, the first friction layer 2 and the first electrode layer 1 contact each other. In this process, as the stress increases, the contact surface between the first friction layer 2 and the first electrode layer 1 gradually increases. Subsequently, the stress applied to the piezoelectric material gradually increases. When the surface layer is in full contact with the bottom layer, the piezoelectric and friction potentials both reach their maximum values. When the force is released, each layer returns to its original state, and electrons flow in the opposite direction under the action of piezoelectricity and friction potential. The repeated contact-separation between the layers enables the piezoelectric-friction composite nanogenerator to generate output externally.

[0036] Among them, the first friction layer is one or more of polyethylene, polypropylene, polystyrene, silicone, polydimethylsiloxane, polyester, polyurethane, polymethacrylate, polytetrafluoroethylene, nylon, polyimide, chitin, cellulose, with a thickness of 100-500μm. The first electrode layer, the second electrode layer and the third electrode layer are one or more of gold, silver, copper, aluminum, iron, and alloy materials, with a thickness of 10-100μm; the piezoelectric layer is one or more of poly L-lactic acid PLLA, glycine, collagen, fiber, and chitin, with a thickness of 20-200μm; the first packaging layer material is a flexible insulating material of one or more of polylactic acid, polyvinyl alcohol, polytetrafluoroethylene, and composite materials, with a thickness of 10-50μm. The second packaging layer material is an elastic insulating material of one or more of polydimethylsiloxane, silicone, latex, rubber, and fluororubber materials, with a thickness of 20-200μm.

[0037] The power management module includes a rectifier filter unit and an energy storage unit, and the power management module is connected to the implantable nanogenerator. The rectifier unit converts the AC current output by the nanogenerator into a DC current, for example, a rectifier bridge can be used; the filter unit converts the pulsed DC output by the rectifier unit into a relatively stable DC current, and provides it to the energy storage unit for storage, for example, the energy storage unit can be a rechargeable lithium battery or an energy storage capacitor. Through the AC / DC energy conversion of the rectifier filter unit, the implantable nanogenerator generates DC power and stores electrical energy in the energy storage unit, and the power management module is implanted subcutaneously.

[0038] Example 2

[0039] like Figure 2As shown, the heart rate sensor, feedback microcontroller and pulse generator together constitute a self-feedback module. The heart rate sensor collects heart rate data and transmits it to the feedback microcontroller. The feedback microcontroller receives and processes the heart rate data. When it is recognized that the heart rate signal is higher than the highest threshold of abnormal heart rate or lower than the lowest threshold of abnormal heart rate, the control switch is turned on, and the power management module and the pulse generator form a path, thereby triggering the pulse generator to start working; when the heart rate signal is between the lowest threshold and the highest threshold of abnormal heart rate, the control switch is turned off, the power management module and the pulse generator are disconnected, the pulse generator does not work, and the feedback microcontroller continues to perform heart rate detection and identification functions. The wires of the heart rate sensor are connected to the feedback microcontroller input S in port, the capacitor in the power management module is connected to the feedback microcontroller V in port, feedback to microcontroller V in port and feedback to the microcontroller V out There is a control switch between the ports, V out Connect to the pulse generator.

[0040] Among them, the heart rate sensor is a friction nanogenerator, such as Figure 4 As shown, the heart rate sensor is composed of the second friction layer 8, the fourth electrode layer / third friction layer 9, the fifth electrode layer 10, the first substrate layer 11, and the third packaging layer 12 arranged opposite to each other from the inside to the outside. The second friction layer 8 is a polymer friction layer and has a micro-nano structure on its inner surface. An air layer is formed between the second friction layer 8 and the inner surface of the fourth electrode layer / third friction layer 9. The fifth electrode layer is attached to the outer side of the second friction layer 8, and the fourth electrode layer / third friction layer is attached to the outer side of the first substrate layer 11. The outermost layer is provided with a packaging layer 12, and the wire 13 is connected to the second friction layer 8 and the fourth electrode layer / third friction layer 9 respectively.

[0041] The working principle of the heart rate sensor is the coupling effect of frictional electrification and electrostatic induction effect. The heart rate sensor is implanted in the heart and fits with the heart. The continuous beating of the heart can cause the second friction layer 8 and the fourth electrode layer / third friction layer 9 of the heart rate sensor to periodically contact and separate. When the heart contracts, the second friction layer 8 and the fourth electrode layer / third friction layer 9 contact each other, and free electrons are generated between the surfaces of the two materials, and the electrons flow from the second friction layer 8 to the fourth electrode layer / third friction layer 9. When the heart relaxes, the second friction layer 8 and the fourth electrode layer / third friction layer 9 separate from each other, resulting in an increase in the distance between the two materials, and electrons flow from the fourth electrode layer / third friction layer 9 to the second friction layer 8. As the heart keeps beating, the electrons circulate back and forth between the two friction layers, so the heart rate sensor generates output.

[0042] The second friction layer is one or more of silicone, polydimethylsiloxane, latex, fluororubber, and polyoctyl citrate, with a thickness of 200-1000 μm. The first substrate layer is one or more of polyethylene, polypropylene, polystyrene, polyester, polyurethane, polymethacrylate, polytetrafluoroethylene, nylon, polyimide, chitin, and cellulose, with a thickness of 50-200 μm. The fourth electrode layer and the fifth electrode layer are one or more of gold, silver, copper, aluminum, iron, and alloy materials, with a thickness of 10-100 μm; the encapsulation layer material is a flexible insulating material of one or more of polylactic acid, polyvinyl alcohol, polytetrafluoroethylene, and composite materials, with a thickness of 10-50 μm.

[0043] Figure 5 This is the experimental result of testing the output performance of the heart rate sensor when it is implanted in the body and driven by the heart beating. The heart rate sensor was implanted outside the pericardium of SD rats and adhered with biological glue. The heart rate sensor was fixed to the outer surface of the heart. Figure 5 As shown in the figure, an oscilloscope (HDO6104) is used to test the voltage signal generated by the heart rate sensor in the body, and an electrometer (Keithley6517B) is used to measure its output current and transferred charge in the body. The output voltage is 3.0V, the output current is 10.0μA, and the transferred charge is 18nC. This proves that the heart rate sensor can monitor heart rate signals such as voltage, current, and transferred charge.

[0044] Example 3

[0045] The feedback microcontroller includes a signal receiving unit, a microprocessor and a switch. The heart rate signal collected by the heart rate sensor is transmitted through port S in The signal is received by the signal receiving unit and transmitted to the microprocessor. The microprocessor compares the received heart rate signal with the abnormal heart rate characteristic value. When it is identified that the heart rate signal is higher than the highest threshold of abnormal heart rate or lower than the lowest threshold of abnormal heart rate, the microprocessor controls V in Port and V out The control switch between the ports is turned on, the power management module forms a path with the pulse generator, the energy stored in the capacitor in the power management module is transferred to the pulse generator, and the pulse generator starts working; when the heart rate signal is between the lowest threshold and the highest threshold of the abnormal heart rate, the microprocessor controls V in Port and V out The control switch between the ports is turned off, the power management module and the pulse generator are disconnected, the pulse generator does not work, and the feedback microcontroller continues to perform the heart rate detection and identification functions.

[0046] The pulse generator output pulse frequency is set to 1-145 Hz, and the voltage is 0-12.0 V. When the pulse generator starts working, it can deliver electrical pulses to the electrical stimulation electrodes with preset electrical stimulation parameters.

[0047] The invention provides a method for triggering a pulse generator by abnormal heart rate.

[0048] Before vagus nerve electrical stimulation, the patient's heart rate is monitored in real time through a heart rate sensor to determine the heart rate intensity and frequency, and to clarify the maximum and minimum heart rate thresholds. The abnormal heart rate parameters and the heart rate threshold for start-up of the control switch are set on the microprocessor through computer programming. There are many ways to determine the heart rate threshold, and in actual applications, it can also be calculated in combination with the patient's real-time heart rate.

[0049] In a preferred embodiment, the heart rate threshold is determined in the following manner: The heart rate threshold V of the start control switch ps =(V0-V bg )*(1±20%)+V bg , where V ps is the maximum or minimum heart rate threshold, V bg It is the average value of the sensor output intensity at the background heart rate per unit time, and V0 is the average value of the sensor output intensity at the normal heart rate per unit time.

[0050] Set the heart rate threshold for starting the control switch on the microprocessor, compare the heart rate threshold with the patient's current heart rate data, and calculate the heart rate change rate R hr , when R hr When it is greater than 20% or less than -20%, the control switch is started, triggering the pulse generator to output a stimulation signal, which is transmitted to the vagus nerve stimulation electrode and releases an electrical stimulation action at the vagus nerve.

[0051] In a preferred embodiment, the heart rate change rate is calculated in the following manner to determine whether the control switch can be activated. hr =[(V m -V bg )-(V0-V bg )] / V0, where V m V is the average value of the sensor output intensity at the maximum or minimum heart rate per unit time. bg It is the average value of the sensor output intensity at the background heart rate per unit time, and V0 is the average value of the sensor output intensity at the normal heart rate per unit time.

[0052] For example, V m It is the average heart rate value of the patient within 10-30 seconds before the current moment. The feedback microcontroller can calculate V in real time based on the heart rate data collected by the heart rate sensor. m It should be noted that the heart rate change rate R hr The calculation method is not limited to the above specific method. In actual use, a more complex or simpler calculation method than the above method can be used.

[0053] Example 4

[0054] like Figure 6 As shown, the base layer 14 of the vagus nerve stimulation electrode is a wire base, which is a degradable polymer wire. A conductive layer 15 is provided on the outside of the base layer, which is a degradable metal. The encapsulation layer 16 covers the conductive layer, and both ends are exposed. The encapsulation layer is a degradable polymer. The exposed wires at both ends are respectively connected to the pulse generator and the vagus nerve target position.

[0055] The wire substrate can be catgut, absorbable PLGA medical suture, PLA wire, magnesium wire, iron wire, molybdenum wire. The conductive layer is a degradable metal of magnesium, iron, manganese, zinc, silicon or molybdenum. The encapsulation layer is polyvinyl alcohol, polygalactone, polylactic acid, polyhydroxybutyric acid valerate, chitosan or sodium alginate.

[0056] The above-mentioned embodiments only express the implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be based on the attached claims.

Claims

1. A closed-loop vagus nerve stimulation system for depression, comprising an implantable nanogenerator, a power management module, a heart rate sensor, a feedback microcontroller, a pulse generator and a vagus nerve stimulation electrode, characterized in that: The implantable nanogenerator collects the mechanical energy of the heartbeat and converts it into electrical energy; the power management module collects and stores the electrical energy converted by the implantable nanogenerator to achieve AC / DC energy conversion and energy storage; the heart rate sensor collects heart rate data and transmits it to the feedback microcontroller; the feedback microcontroller receives and processes the heart rate data, identifies abnormal heart rate data generated before or during the onset of depression, and triggers the pulse generator to output electrical pulses to the vagus nerve stimulation electrode, and the vagus nerve stimulation electrode stimulates the vagus nerve; The implantable nanogenerator is a piezoelectric-friction composite nanogenerator, which is placed between the heart and the pericardium. From the inside to the outside, it is sequentially arranged as a first electrode layer, a first friction layer, a piezoelectric layer, a second electrode layer, a third electrode layer, a first packaging layer, and a second packaging layer. The first friction layer is a polymer friction layer and the inner surface is provided with a micro-nano structure. An air layer is formed between the first friction layer and the inner surface of the first electrode layer. The inside and outside of the piezoelectric layer are respectively bonded to the first electrode layer and the third electrode layer. The other side of the first friction layer is in contact with the second electrode layer. The outermost layer is sequentially packaged by the first packaging layer and the second packaging layer. One side of the second electrode layer faces the anterior wall of the left ventricle. The heart rate sensor is a friction nanogenerator, which includes, from the inside to the outside, a second friction layer, a fourth electrode layer / a third friction layer, a fifth electrode layer, a first substrate layer, and a third packaging layer that are arranged opposite to each other; the second friction layer is a polymer friction layer and a micro-nano structure is provided on the inner surface; an air layer is formed between the second friction layer and the inner surface of the fourth electrode layer / the third friction layer; the fifth electrode layer is attached to the outer side of the second friction layer; the fourth electrode layer / the third friction layer is attached to the outer side of the first substrate layer; the outermost layer is provided with a packaging layer; the heart rate sensor is fixed on the outer surface of the heart to generate electrical pulses whose frequency is consistent with the heart rate and whose intensity depends on the strength of the heart beating.

2. The closed-loop vagus nerve stimulation system according to claim 1, characterized in that: The power management module includes a rectifying and filtering unit and an energy storage unit. The power management module is connected to the implantable nanogenerator. The rectifying and filtering unit completes AC / DC energy conversion. The energy storage unit stores electrical energy. The power management module is implanted subcutaneously.

3. The closed-loop vagus nerve stimulation system according to claim 1, characterized in that: The feedback microcontroller includes a signal receiving unit, a microprocessor and a control switch. The signal receiving unit of the feedback microcontroller transmits the received heart rate sensor electrical signal to the microprocessor, and pre-sets the abnormal heart rate threshold and abnormal heart rate range before or during the onset of depression for the microprocessor. The microprocessor compares the received heart rate signal with the preset abnormal heart rate characteristic value before or during the onset of depression. When it is higher than the highest threshold of abnormal heart rate or lower than the lowest threshold of abnormal heart rate, the control switch on the feedback microcontroller is turned on, and the power management module forms a path with the pulse generator to trigger the pulse generator.

4. The closed-loop vagus nerve stimulation system according to claim 1, characterized in that: The pulse generator outputs a pulse frequency of 1-145 Hz and a voltage of 0-12.0 V.

5. The closed-loop vagus nerve stimulation system according to claim 1, characterized in that: The vagus nerve stimulation electrode and the pulse generator are connected by a nerve stimulation wire. The vagus nerve stimulation electrode is spiral-shaped and wound around the vagus nerve.

6. The closed-loop vagus nerve stimulation system according to claim 1, characterized in that: The base layer of the vagus nerve stimulation electrode is a wire base, which is a degradable polymer wire. A conductive layer is provided on the outside of the base layer, which is a degradable metal. The encapsulation layer covers the conductive layer, and both ends are exposed. The encapsulation layer is a degradable polymer. The wires exposed at both ends are respectively connected to the pulse generator and the vagus nerve target position.

7. The closed-loop vagus nerve stimulation system according to claim 3, characterized in that: The method of triggering the pulse generator by the microprocessor is to set the start threshold on the microprocessor, compare the start threshold with the patient's current heart rate data, and calculate the heart rate change rate R hr , R hr When the positive and negative difference is greater than 20%, the pulse generator is started to output the stimulation signal; R hr =[(V m -V bg )-(V0-V bg )] / V0, where V m It is the average value of the sensor output intensity at the maximum or minimum heart rate per unit time, V bg It is the average value of the sensor output intensity at the background heart rate per unit time, and V0 is the average value of the sensor output intensity at the normal heart rate per unit time.

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