Vagus nerve stimulation device

Abstract

The invention relates to a vagus nerve stimulation device. The vagus nerve stimulation device comprises an ultrasonic generation unit, the ultrasonic generation unit is configured to emit ultrasonic waves to a target area of the vagus nerve, the frequency of the emitted ultrasonic waves is 40 kHz to 200 kHz, and the emitted ultrasonic waves penetrate biological tissue percutaneously and generate a stimulation effect on the target area of the vagus nerve. According to the vagus nerve stimulation device provided by the invention, deep targeting is realized with lower sound energy, and safe, effective, accurate and comfortable non-thermal nerve regulation of deep vagus nerves is realized.

Description

Technical Field

[0001] This application relates to the field of neuromodulation technology, and in particular to a vagus nerve stimulation device. Background Technology

[0002] Neuromodulation techniques are important for treating neurological disorders. Among them, transcutaneous vagus nerve stimulation (tVNS), as a non-invasive treatment, has attracted widespread attention due to its potential in modulating the autonomic nervous system and treating epilepsy, depression, and inflammation. Currently, the mainstream technology in this field relies on transcutaneous electrical stimulation. However, transcutaneous electrical stimulation has significant limitations: its current tends to diffuse on the tissue surface, making it difficult to effectively focus on deep target nerves, especially deep structures in the neck like the vagus nerve. To achieve sufficient stimulation depth, the stimulation intensity often needs to be increased, which can lead to strong stinging sensations, muscle spasms, and other discomfort in the superficial skin and surrounding tissues, resulting in poor patient tolerance and affecting treatment adherence and safety.

[0003] To overcome the problem of insufficient penetration depth of electrical stimulation, some studies have begun to explore the use of high-intensity focused ultrasound (HIFU) for neuromodulation. Ultrasound has excellent tissue penetration capabilities and can non-invasively focus on deep targets. However, the ultrasound frequencies traditionally used for neuromodulation are usually high, typically greater than 1 MHz. Its energy is easily absorbed by the tissue during penetration and converted into heat, with its main biological effect stemming from a thermal mechanism. While this thermal effect can be used for ablation, it carries the risk of causing tissue thermal damage in scenarios requiring reversible, non-invasive modulation of nerve function, limiting its application in long-term, safe neuromodulation.

[0004] Therefore, it is necessary to propose a new technical solution to overcome the shortcomings of existing technologies. Summary of the Invention

[0005] Based on this, this application provides a vagus nerve stimulation device, including an ultrasound generating unit, wherein:

[0006] The ultrasound generating unit is configured to emit ultrasound waves toward the target area of ​​the vagus nerve.

[0007] The emitted ultrasound waves have a frequency of 40kHz to 200kHz, allowing them to penetrate biological tissues percutaneously and stimulate the target area of ​​the vagus nerve.

[0008] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 40 kHz to 80 kHz.

[0009] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with frequencies of 40 kHz, 45 kHz, 50 kHz, 55 kHz, 60 kHz, 65 kHz, 70 kHz, 75 kHz, or 80 kHz, or 100 kHz, 120 kHz, 160 kHz, or 180 kHz.

[0010] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 80 kHz to 150 kHz.

[0011] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves at frequencies of 85 kHz, 90 kHz, 100 kHz, 110 kHz, 120 kHz, 130 kHz, 140 kHz, or 150 kHz.

[0012] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves with a frequency of 150 kHz to 200 kHz.

[0013] In some embodiments, the ultrasound generating unit is configured to provide ultrasound waves at frequencies of 155 kHz, 160 kHz, 165 kHz, 170 kHz, 175 kHz, 180 kHz, 85 kHz, 190 kHz, 195 kHz, or 200 kHz.

[0014] In some embodiments, the ultrasonic generating unit includes an ultrasonic transducer and an excitation circuit, the excitation circuit being electrically connected to the ultrasonic transducer to excite the ultrasonic transducer to generate ultrasonic waves.

[0015] In some embodiments, the excitation circuit includes a power supply module, a signal generation module, and an amplification module. The signal generation module generates an excitation wave of a set waveform, and the amplification module amplifies the excitation wave and provides it to the ultrasonic transducer to excite the ultrasonic transducer to generate ultrasonic waves.

[0016] In some embodiments, the excitation circuit further includes a boost circuit module and a matching network module, the matching network module being connected between the amplification module and the ultrasonic transducer.

[0017] In some embodiments, the vagus nerve stimulation device is adapted to be placed in the neck so that ultrasound waves penetrate the neck skin and act on the vagus nerve.

[0018] In some embodiments, the vagus nerve stimulation device includes a body adapted to be attached to human skin, and the ultrasound generating unit is disposed on the body.

[0019] In some embodiments, the body is configured as a patch or neckband suitable for attachment to the neck of a person.

[0020] In some embodiments, the body includes a flexible silicone element that can deform to fit human skin.

[0021] In some embodiments, the vagus nerve stimulation device has a hierarchical structure.

[0022] In some embodiments, the hierarchical structure includes a base layer, an ultrasound generating layer, and a coupling layer arranged in sequence.

[0023] In some embodiments, the target area includes the vagus nerve region associated with one or more of the following diseases: neuropsychiatric disorders, cognitive impairment, metabolic diseases, inflammatory and autoimmune diseases, cardiovascular diseases, and chronic pain syndromes.

[0024] In some embodiments, the ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with one or more of the following conditions: major depressive disorder, anxiety disorder, post-traumatic stress disorder, or epilepsy, in order to modulate the excitability and neurotransmitter balance of the central nervous system.

[0025] In some embodiments, the ultrasound generating unit is configured to controllably deliver ultrasound waves to target areas in the vagus nerve associated with Alzheimer's disease or other neurodegenerative diseases to enhance neural plasticity and promote the secretion of neurotrophic factors.

[0026] In some embodiments, the ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with obesity or type 2 diabetes to modulate the feeding center in the hypothalamus and improve insulin sensitivity.

[0027] In some embodiments, the ultrasound generating unit is configured to controllably deliver ultrasound waves to target areas in the vagus nerve associated with rheumatoid arthritis, Crohn's disease, or sepsis to suppress an overactive inflammatory response and regulate cytokine release.

[0028] In some embodiments, the ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with heart failure and arrhythmia in order to enhance vagal tone of the heart.

[0029] In some embodiments, the ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with fibromyalgia and migraine, in order to modulate the transmission of pain signals in the central nervous system.

[0030] In some embodiments, the ultrasonic generating unit includes multiple ultrasonic transducers arranged in an array.

[0031] In some embodiments, the ultrasonic transducers are four or more and arranged in a rectangular, circular or ring array.

[0032] The vagus nerve stimulation device provided in this application delivers ultrasound waves at frequencies of 40kHz to 200kHz to the deep vagus nerve target area. This frequency of ultrasound not only penetrates deep human tissue more effectively, achieving deep targeting with lower acoustic energy, but more importantly, its non-thermodynamic effects are particularly prominent. These non-thermodynamic effects, through mechanisms such as acoustic radiation force or cavitation, can directly regulate the electrophysiological properties of the neuronal membrane, achieving nerve excitation or inhibition without causing a significant temperature increase. This enables safe, effective, precise, and comfortable non-thermodynamic neuromodulation of the deep vagus nerve, filling the gaps and deficiencies of existing electrical stimulation and high-frequency ultrasound technologies. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the embodiments of this application or the conventional technology, the drawings used in the description of the embodiments or the conventional technology will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0034] Figure 1 This is a schematic diagram of the action position of an embodiment of the vagus nerve stimulation device of this application.

[0035] Figure 2 This is a schematic diagram of the structure of an embodiment of the vagus nerve stimulation device of this application.

[0036] Figure 3 This is an explosion diagram of an embodiment of the vagus nerve stimulation device of this application.

[0037] Figure 4 This is another exploded schematic diagram of an embodiment of the vagus nerve stimulation device of this application.

[0038] Figure 5 This is a schematic diagram of the circuit module of an embodiment of the vagus nerve stimulation device of this application.

[0039] Figure 6 This is a graph showing the changes in HAMD in a patient during a treatment case of depression, based on an embodiment of the vagus nerve stimulation device of this application.

[0040] Figure 7 This is a comparison chart of the frequency of epileptic seizures in patients in an epilepsy treatment case, based on an embodiment of the vagus nerve stimulation device of this application.

[0041] Figure 8 This is a comparative graph showing the colonic tissue pathology scores of patients in a case of inflammatory bowel disease treatment using an embodiment of the vagus nerve stimulation device of this application.

[0042] The component labels are as follows:

[0043] 1. Neck; 11. Vagus nerve trunk; 100. Vagus nerve stimulation device; 10. Main body; 101. Basal layer; 102. Coupled layer; 20. Ultrasound generating unit; 21. Ultrasound transducer; 221. DC / battery; 222. Sine wave signal generator; 223. Amplification circuit; 224. Boost circuit; 225. Matching network. Detailed Implementation

[0044] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0045] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on the other component or there may be an intermediate component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intermediate component present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this application's specification are for illustrative purposes only and do not represent the only possible implementation.

[0046] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0047] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature and the second feature are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0048] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The term "and / or" as used in this application includes any and all combinations of one or more of the associated listed items.

[0049] This application relates to the field of neuromodulation technology, specifically a vagus nerve stimulation device. It aims to provide a non-invasive, low-energy, deep-targeting, safe, effective, precise, and comfortable non-thermal neuromodulation solution for the deep vagus nerve, overcoming many problems existing in current technologies, such as infection, surgical trauma, and high cost associated with implanted electrode stimulation, and the difficulty in precise targeting and side effects of transcutaneous electrical stimulation. The technical solution is described in detail below with reference to accompanying drawings and specific implementation examples.

[0050] Please see Figures 1 to 4 As shown, this application provides a vagus nerve stimulation device 100, which achieves effective and safe stimulation of the deep vagus nerve through non-invasive ultrasound stimulation technology. The vagus nerve stimulation device 100 is used to generate ultrasound waves to stimulate the vagus nerve, and includes a main body 10 and an ultrasound generating unit 20. The main body 10 is configured to adhere to the skin of the human body. The ultrasound generating unit 20 is disposed on the main body 10 and is configured to emit ultrasound waves towards the target area of ​​the vagus nerve. The emitted ultrasound waves have a frequency of 40kHz to 200kHz, allowing them to penetrate biological tissue percutaneously and stimulate the target area of ​​the vagus nerve.

[0051] The vagus nerve stimulation device 100 provided in this application delivers ultrasound waves with a frequency of 40kHz to 200kHz to the deep vagus nerve target area. This frequency of ultrasound waves not only penetrates deep human tissue more effectively, achieving deep targeting with lower acoustic energy, but more importantly, its non-thermodynamic effects are particularly prominent. These non-thermodynamic effects, through mechanisms such as acoustic radiation force or cavitation, can directly regulate the electrophysiological properties of the neuronal membrane, achieving nerve excitation or inhibition without causing a significant temperature increase. This enables safe, effective, precise, and comfortable non-thermodynamic neuromodulation of the deep vagus nerve, filling the gaps and deficiencies of existing electrical stimulation and high-frequency ultrasound technologies.

[0052] like Figures 2 to 4 As shown, in one embodiment of the vagus nerve stimulation device 100 provided in this application, the main body 10 is configured to adhere to the skin of the human body, providing a stable attachment base for the entire device and ensuring that the device can maintain stable contact with the human body during use, thereby ensuring that ultrasound waves can accurately act on the target area. The ultrasound generating unit 20 is disposed within the main body 10, and its core function is to controllably provide ultrasound waves to the target area of ​​the vagus nerve, thereby stimulating the vagus nerve through the specific action of ultrasound waves, and thus achieving the purpose of neuromodulation.

[0053] In this embodiment, the design of the main body 10 fully considers its conformity to human skin and ease of use. In some embodiments, the main body 10 is configured as a patch suitable for attachment to the neck 1, allowing ultrasound waves to penetrate the skin of the neck 1 and stimulate the vagus nerve. In other embodiments, the main body is configured as a neckband suitable for wearing and attaching to the neck 1. The neck 1 is an important distribution area of ​​the vagus nerve; designing the main body 10 of the vagus nerve stimulation device 100 as a patch for the neck 1 allows ultrasound waves to penetrate the skin of the neck 1 more effectively and directly stimulate the vagus nerve. Furthermore, the main body 10 is configured to attach to the area of ​​the neck 1 directly opposite the vagus nerve trunk 11 within the carotid sheath, thereby stimulating the vagus nerve more precisely and improving the effect of neuromodulation.

[0054] Furthermore, to better adapt to the shape and physiological characteristics of human skin, and to prevent the vagus nerve stimulation device 100 from failing to maintain constant contact with the skin during human activity, in this embodiment, the main body 10 includes a flexible silicone component. Flexible silicone has excellent flexibility and deformability, allowing it to deform accordingly according to the undulations and curves of the human skin surface, thus closely conforming to the skin. This close fit not only helps improve the transmission efficiency of ultrasound waves and reduce energy loss, but also enhances patient comfort during use, avoiding discomfort or device displacement caused by poor contact between the device and the skin.

[0055] In some embodiments, the main body 10 is a deformable component, such as a flexible circuit board, or a component with a flexible substrate such as rubber, silicone, woven fabric, or hydrogel that can be combined with flexible circuitry. Preferably, the main body 10 is a flexible sheet to adapt to skin folds and areas such as the neck that are frequently in motion. The flexible main body 10 allows for a stable acoustic coupling interface between the ultrasound generating unit 20 and the skin, effectively reducing energy loss of ultrasound waves during propagation. In some embodiments, the main body 10 is made of medical-grade silicone, which is safe, hygienic, skin-friendly, and lightweight, exhibiting excellent wearable characteristics. Figure 3 and Figure 4 As shown, in this embodiment, the vagus nerve stimulation device has a layered structure. Specifically, the layered structure includes a base layer 101, an ultrasound generating layer, and a coupling layer 102 arranged in sequence. The base layer 101 and coupling layer 102 constitute the main body 10, and the ultrasound generating layer is the layer containing the ultrasound generating unit 20, sandwiched between or encased within the base layer 101 and coupling layer 102. The base layer 101 is a deformable layer, for example, made of silicone. The coupling layer 102 is made of, for example, hydrogel, which improves sound wave transmission. By filling the gap between the vagus nerve stimulation device and the human skin, the coupling layer 102 achieves a gradual transition in acoustic impedance, effectively reducing interface reflection and allowing more ultrasound energy to penetrate human biological tissue. In use, the coupling layer 102 is attached to the human skin, with the base layer 101 facing away from the skin.

[0056] The ultrasound generating unit 20 is the core functional part of the vagus nerve stimulation device 100, and its performance directly affects the stimulation effect on the vagus nerve. In this embodiment, the ultrasound generating unit 20 includes an ultrasound transducer 21 and an excitation circuit. The excitation circuit is electrically connected to the ultrasound transducer 21 to excite the ultrasound transducer 21 to generate ultrasound waves, thereby exciting the ultrasound transducer to generate ultrasound waves.

[0057] Furthermore, such as Figure 5As shown, the excitation circuit includes a power supply module, a signal generation module, and an amplification module. The power supply module provides stable power to the entire excitation circuit, ensuring that each module can operate normally; specifically, it is a DC / battery 221. In some embodiments, the excitation circuit includes a boost circuit module, specifically a boost circuit 224, to generate sufficient supply voltage. The signal generation module generates an excitation wave of a set waveform, such as a square wave or a sine wave; specifically, it is a sine wave signal generator 222. The amplification module amplifies the excitation wave and specifically includes an amplification circuit 223. In some embodiments, the excitation circuit further includes a matching network module connected between the amplification module and the ultrasonic transducer; it includes a matching network 225 to achieve path matching, so that the amplified excitation wave is provided to the ultrasonic transducer 21 in a matched manner, enabling the ultrasonic transducer 21 to generate ultrasonic waves of sufficient intensity and specific characteristics.

[0058] Specifically, in one embodiment, the excitation circuit of the ultrasonic transducer 21 mainly consists of the following key circuits, designed to drive the transducer efficiently and accurately, achieving efficient conversion between electrical and acoustic signals. DC / battery 221 and boost circuit 224: provide stable power to the entire excitation circuit and boost the voltage to generate sufficient supply voltage; Sine wave signal generator 222: typically employs Direct Digital Synthesis (DDS) technology, such as using a DDS chip like the AD9850, to generate frequency- and phase-adjustable sine or square wave signals to meet the resonant frequency requirements of different transducers; Amplifier circuit 223: amplifies the low-power signal generated by the signal generation circuit to a high-voltage pulse sufficient to drive the transducer, commonly using a half-bridge or full-bridge topology, employing VMOS transistors, MOSFET modules, etc., as switching elements; Matching network: composed of a matching transformer and capacitors, used to match the impedance of the power amplifier circuit and the transducer, maximizing the electro-acoustic conversion efficiency. Additionally, auxiliary functional modules such as a control module and a frequency selection module may also be included. The control module sets parameters (such as frequency and pulse count) through a host computer or microcontroller to coordinate the operation of each circuit; the frequency selection module is used in specific applications, such as multi-frequency transducer driving, to extract the target frequency from a wideband signal and simplify multi-frequency drive design.

[0059] The ultrasonic transducer 21 converts electrical energy into ultrasonic energy. In some embodiments, the ultrasonic transducer 21 is configured to generate pulsed ultrasound waves, which can have different duty cycles to suit the treatment needs of different diseases. Pulsed ultrasound waves have unique advantages; by adjusting parameters such as the pulse repetition frequency, pulse width, pulse intensity, and duty cycle, the intensity and frequency of stimulation to the vagus nerve can be more precisely controlled, thereby achieving fine-tuning of neural modulation. For example, a lower repetition frequency is suitable for situations requiring gentler nerve stimulation, while a higher repetition frequency can be used in scenarios requiring stronger stimulation.

[0060] In some embodiments, the ultrasound generating unit 20 employs a miniaturized design, with its excitation circuitry housed on a circuit board measuring only 2cm × 2cm. Furthermore, the ultrasound generating unit 20 can connect to a handheld terminal, such as a smartphone, via wired or wireless signals such as Bluetooth, infrared, Wi-Fi, or mobile communication networks, allowing users to intuitively set stimulation parameters and view treatment progress within an application on their smartphone or other handheld terminal.

[0061] Please continue reading. Figure 2 and Figure 3 As shown, in some embodiments, there are multiple ultrasonic transducers 21, and these multiple ultrasonic transducers 21 are arranged in an array. This array arrangement can further improve the accuracy and effectiveness of vagus nerve stimulation. The array arrangement can specifically be various forms such as a triangular array, rectangular array, circular array, and ring array, which can be configured according to the shape of the area to be covered. In this embodiment, there are four ultrasonic transducers 21 arranged in a rectangular array; in other embodiments, the number of ultrasonic transducers 21 can be more than four. The array of ultrasonic transducers 21 formed in this embodiment adopts a planar or slightly focused acoustic structure, has a large emission area, and can generate a sound field with a wide coverage. This design allows the device to be worn without precise positioning; simply placing the device against the corresponding area of ​​the neck 1 ensures that the vagus nerve trunk 11 is effectively wrapped within the sound field, greatly reducing the difficulty of use and improving the practicality and convenience of the device. In different application scenarios, different array forms can be used to achieve adjustable focus. The adjustable focal length increases the flexibility and adaptability of the vagus nerve stimulation device 100. It allows for adjustment of the focal length based on different patients and the location of the vagus nerve target area, enabling the ultrasound waves to be focused more accurately on the target region and further improving the precision of stimulation. For example, the location and depth of the vagus nerve in the neck may vary for patients of different body types; adjusting the focal length ensures that the ultrasound waves always accurately target the target area. The ultrasound transducer array 21 can be manufactured using flexible printed circuit technology, providing excellent surface fit.

[0062] The vagus nerve stimulation device 100 provided in this application has an ultrasound generating unit 20 configured to provide ultrasound waves with a frequency of 40kHz to 200kHz to act on the target area of ​​the deep vagus nerve. Ultrasound waves in this frequency range are low-frequency ultrasound waves, which have less attenuation in biological tissues and can penetrate tissue barriers such as skin and muscle to reach the deep vagus nerve, overcoming the limitation of limited penetration depth in traditional electrical stimulation methods. Simultaneously, low-frequency ultrasound uses a non-thermal effect as its main mechanism of action, influencing the nerve cell membrane potential through acoustic radiation or cavitation effects to achieve nerve regulation, avoiding temperature increases caused by tissue energy absorption, and significantly improving the safety of treatment. The mechanical vibration effect of the ultrasound waves acts on the vagus nerve through acoustic radiation to change the permeability of the nerve cell membrane, regulate the activity of sodium and potassium ion channels, and affect nerve excitability; the cavitation effect of the ultrasound waves acts on the vagus nerve, and the generated microfluidics promote the release and rebalancing of neurotransmitters.

[0063] In some specific application embodiments, the ultrasound generating unit 20 can be configured to provide ultrasound waves with frequencies of 40kHz~80kHz, 80kHz~150kHz, or 150kHz~200kHz, or even configured to provide ultrasound waves with specific frequencies such as 40kHz, 45kHz, 50kHz, 55kHz, 60kHz, 65kHz, 70kHz, 75kHz, 80kHz, 90kHz, 95kHz, 100kHz, 110kHz, 120kHz, 130kHz, 140kHz, 150kHz, 155kHz, 160kHz, 165kHz, 170kHz, 175kHz, 180kHz, 85kHz, 190kHz, 195kHz, or 200kHz. Ultrasound waves of different frequencies have different penetration depths and tissue interaction characteristics. Generally speaking, relatively lower frequency ultrasound waves have deeper penetration depths but relatively lower spatial resolution; relatively higher frequency ultrasound waves have higher spatial resolution but shallower penetration depths. By selecting an appropriate ultrasound frequency, precise stimulation of the vagus nerve can be achieved based on the depth and accuracy requirements of the target area. For example, a lower frequency ultrasound can be selected for a deeper vagus nerve target area, while a higher frequency ultrasound can be selected for a target area requiring higher precision stimulation.

[0064] In the vagus nerve stimulation device 100 of this application, the target area includes target areas of the vagus nerve associated with one or more diseases, such as neuropsychiatric disorders, cognitive impairment, metabolic diseases, inflammatory and autoimmune diseases, cardiovascular diseases, and chronic pain syndromes. The vagus nerve plays a crucial role in the physiological regulation of the human body and is closely related to the occurrence and development of various diseases. The term "associated" refers to the important role these target areas play in the pathological mechanisms of one or more diseases, such as neuropsychiatric disorders, cognitive impairment, metabolic diseases, inflammatory and autoimmune diseases, cardiovascular diseases, and chronic pain syndromes. Ultrasonic stimulation of these target areas can effectively alleviate or treat the corresponding symptoms. By stimulating target areas of the vagus nerve associated with specific diseases, the function of the nervous system can be modulated, thereby achieving the purpose of treating or alleviating these diseases.

[0065] In some embodiments, the ultrasound generating unit 20 is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with one or more of the following conditions: major depressive disorder, anxiety disorder, post-traumatic stress disorder, or epilepsy, to modulate the excitability and neurotransmitter balance of the central nervous system. That is, in the area of ​​neuropsychiatric disorders, this device can be used to treat major depressive disorder, anxiety disorder, post-traumatic stress disorder, and epilepsy by modulating the excitability and neurotransmitter balance of the central nervous system.

[0066] In other embodiments, the ultrasound generating unit 20 is configured to controllably deliver ultrasound waves to target areas in the vagus nerve associated with Alzheimer's disease or other neurodegenerative diseases to enhance neural plasticity and promote the secretion of neurotrophic factors. That is, in the field of cognitive impairment, this device aims to improve the memory and cognitive abilities of patients with neurodegenerative diseases such as Alzheimer's disease by enhancing neural plasticity and promoting the secretion of neurotrophic factors.

[0067] In other embodiments, the ultrasound generating unit 20 is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with obesity or type 2 diabetes to modulate the hypothalamic feeding center and improve insulin sensitivity. That is, in terms of metabolic diseases, this device is suitable for treating metabolic syndromes such as obesity and type 2 diabetes by intervening in metabolic processes through modulating the hypothalamic feeding center and improving insulin sensitivity.

[0068] In other embodiments, the ultrasound generating unit 20 is configured to controllably deliver ultrasound waves to target areas in the vagus nerve associated with rheumatoid arthritis, Crohn's disease, or sepsis to suppress overactive inflammatory responses and regulate cytokine release. That is, in the context of inflammatory and autoimmune diseases, the device can be used as an adjunct therapy for rheumatoid arthritis, Crohn's disease, and sepsis by suppressing overactive inflammatory responses and regulating cytokine release.

[0069] In other embodiments, the ultrasound generating unit 20 is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with heart failure and arrhythmias to enhance vagal tone in the heart. That is, in the field of cardiovascular disease, this device is suitable for patients with heart failure and arrhythmias to improve heart rate variability and cardiac function by enhancing vagal tone in the heart.

[0070] In other embodiments, the ultrasound generating unit 20 is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with fibromyalgia and migraine to modulate the transmission of pain signals in the central nervous system. That is, the device is also suitable for treating chronic pain syndromes such as fibromyalgia and migraine by relieving symptoms through modulating the transmission of pain signals in the central nervous system.

[0071] When using the vagus nerve stimulation device 100 provided in this application, the main body 10 is first attached to a suitable location on the skin, ensuring a tight fit between the device and the skin. The suitable location refers to a position where the vagus nerve can be effectively stimulated; this location can be determined in advance using anatomical techniques and human endoscopic techniques. Then, by controlling the excitation circuit, the ultrasound generating unit 20 generates ultrasound waves with preset parameters such as frequency, phase, duty cycle, repetition frequency, and intensity, and focuses the ultrasound waves onto the target area of ​​the vagus nerve to achieve stimulation modulation.

[0072] The following are some specific clinical trials illustrating the application of the vagus nerve stimulation device 100 provided in this application in terms of neuromodulation.

[0073] Example 1: Treatment of Depression

[0074] The percutaneous vagus nerve ultrasound stimulation device used in this case operates at a frequency of 150-200 kHz and has shown good performance in treating treatment-resistant depression. The device employs a 20 mm diameter circular planar piezoelectric ceramic transducer encapsulated in a flexible neckband made of medical-grade silicone (Ecoflex silicone). This case utilizes a pulsed ultrasound emission mode with a duty cycle of 30% and a sound pressure level controlled below 2 W / cm². During treatment, the patient wears the device once daily for 20 minutes each time, with a treatment cycle of 6 weeks.

[0075] This device generates low-frequency ultrasound waves that penetrate neck tissue and act on the vagus nerve trunk within the carotid sheath. The mechanical vibration effect of the ultrasound waves alters the permeability of nerve cell membranes through acoustic radiation, regulating the activity of sodium and potassium ion channels and thus affecting nerve excitability. Simultaneously, the microfluidic effect generated by cavitation promotes the release and rebalancing of neurotransmitters. During treatment, the surface temperature of the device is maintained below 37°C, completely avoiding the risk of thermal damage.

[0076] like Figure 6 As shown, clinical studies have demonstrated that after 6 weeks of treatment, patients' Hamilton Depression Rating Scale (HAMD) scores decreased from an initial moderate depression level of approximately 18.5 points to a normal level of approximately 6.2 points, a reduction of an average of 12.3 points, and serum brain-derived neurotrophic factor (BDNF) levels significantly increased. The non-invasive nature of this device allows patients to complete treatment at home, greatly improving treatment adherence. Compared to traditional drug therapy, this treatment method avoids drug side effects and provides a new treatment option for patients with drug-resistant depression.

[0077] Example 2: Epilepsy Treatment

[0078] The percutaneous vagus nerve ultrasound stimulation device used in this example operates at an ultrasound frequency of 80-150 kHz, with 120 kHz being the preferred frequency, and has shown good performance in treating epilepsy. This example employs a 4-element ring-shaped focusing transducer array, with an outer diameter of 40 mm and an inner diameter of 20 mm, integrated within an Ecoflex elastic silicone encapsulation layer.

[0079] During treatment, the device employs intelligent adaptive adjustment, using a relatively high-intensity stimulation mode during epileptic seizures and a continuous low-intensity stimulation mode to maintain the neuromodulation effect during non-seizure periods. Biomechanical simulations show that the sound field generated by this focused transducer array reaches a sound intensity of 2.0 W / cm² at the vagus nerve, while the sound intensity in surrounding tissues is below the safe threshold of 0.7 W / cm². Figure 7 As shown, clinical trials have demonstrated that, within the same statistical duration, there were 18 seizures before treatment and 6 seizures after treatment, indicating that the system reduces the frequency of epileptic seizures by approximately 67%. Patients experience high comfort when wearing the system, and it does not disrupt normal sleep even when used at night.

[0080] Example 3: Treatment of Inflammatory Bowel Disease

[0081] The ultrasonic vagus nerve stimulation device used in this example operates at a frequency range of 40–80 kHz, preferably 40 kHz, 50 kHz, 60 kHz, 70 kHz, or 80 kHz. This example employs a composite transducer design with a central 20 mm planar emission area surrounded by four circular focusing elements. The entire system is embedded in a biocompatible hydrogel matrix, forming a flexible patch that highly conforms to the anatomical structure of the neck.

[0082] For the treatment of inflammatory bowel disease, this device primarily activates the cholinergic anti-inflammatory pathway in the vagus nerve, releasing acetylcholine which acts on α7nAChR receptors (α7 nicotinic acetylcholine receptors) on macrophages, inhibiting the release of pro-inflammatory factors such as TNF-α (tumor necrosis factor-α). Figure 8 As shown, clinical studies have demonstrated that after four weeks of treatment using this device, the disease activity index of experimental colitis models significantly improved, and the colonic histopathological score decreased by 58.7%. This technology provides a novel non-pharmacological treatment option for patients with inflammatory bowel disease, and is particularly significant for those who do not respond well to traditional biological agents or have developed drug resistance.

[0083] As can be seen from the above description of specific embodiments, the vagus nerve stimulation device of this application has significant advantages compared with the prior art. First, it is a non-invasive neuromodulation method, avoiding the problems of infection, surgical trauma, and high costs associated with implanted electrode stimulation, greatly improving patient acceptance and safety. Second, through the action of ultrasound, targeted stimulation of the deep vagus nerve can be achieved, overcoming the problems of percutaneous electrical stimulation's difficulty in penetrating superficial tissues and its tendency to cause stimulation diffusion and side effects. Furthermore, the main design of the device facilitates daily use by patients, improving the convenience and compliance of treatment.

[0084] The vagus nerve stimulation device 100 provided in this application uses non-invasive percutaneous transmission of ultrasound waves from 40kHz to 200kHz. This frequency of ultrasound waves not only penetrates deep human tissues more effectively, achieving deep targeting with lower acoustic energy, but more importantly, its non-thermodynamic effects are particularly prominent. These non-thermodynamic effects, through mechanisms such as acoustic radiation force or cavitation effects, can directly regulate the electrophysiological properties of neuronal membranes, achieving nerve excitation or inhibition without causing a significant temperature increase. This enables safe, effective, precise, and comfortable non-thermal neuromodulation of the deep vagus nerve, filling the gaps and deficiencies of existing electrical stimulation and high-frequency ultrasound technologies. Furthermore, the vagus nerve stimulation device 100 provided in this application combines a flexible main body 10 with an array of ultrasound transducers 21, making it comfortable to wear and conforming to positions such as the neck, maintaining excellent acoustic coupling performance, and suitable for home use.

[0085] The vagus nerve stimulation device described in this application achieves safe and effective stimulation of the vagus nerve through its unique structural design and technical means, providing a new and promising technical solution for the treatment and research of nervous system diseases. With continuous technological development and improvement, it is believed that this device will play a greater role in clinical applications, bringing better treatment outcomes and quality of life to patients.

[0086] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the scope of protection of this application. Therefore, the patent protection scope of this application should be determined by the appended claims.

Claims

1. A vagus nerve stimulation device, characterized in that, Includes an ultrasound generating unit, wherein: The ultrasound generating unit is configured to emit ultrasound waves toward the target area of ​​the vagus nerve. The emitted ultrasound waves have a frequency of 40kHz to 200kHz, allowing them to penetrate biological tissues percutaneously and stimulate the target area of ​​the vagus nerve.

2. The vagus nerve stimulation device according to claim 1, characterized in that, The ultrasonic generating unit is configured to provide ultrasonic waves with a frequency of 40kHz to 80kHz.

3. The vagus nerve stimulation device according to claim 2, characterized in that, The ultrasonic generating unit is configured to provide ultrasonic waves with a frequency of 40 kHz, 45 kHz, 50 kHz, 55 kHz, 60 kHz, 65 kHz, 70 kHz, 75 kHz, or 80 kHz.

4. The vagus nerve stimulation device according to claim 1, characterized in that, The ultrasonic generating unit is configured to provide ultrasonic waves with a frequency of 80kHz to 150kHz.

5. The vagus nerve stimulation device according to claim 4, characterized in that, The ultrasonic generating unit is configured to provide ultrasonic waves with a frequency of 85 kHz or 90 kHz or 95 kHz or 100 kHz or 110 kHz or 120 kHz or 130 kHz or 140 kHz or 150 kHz.

6. The vagus nerve stimulation device according to claim 1, characterized in that, The ultrasonic generating unit is configured to provide ultrasonic waves with a frequency of 150kHz to 200kHz.

7. The vagus nerve stimulation device according to claim 6, characterized in that, The ultrasonic generating unit is configured to provide ultrasonic waves with a frequency of 155 kHz, 160 kHz, 165 kHz, 170 kHz, 175 kHz, 180 kHz, 85 kHz, 190 kHz, 195 kHz, or 200 kHz.

8. The vagus nerve stimulation device according to claim 1, characterized in that, The ultrasonic generating unit includes an ultrasonic transducer and an excitation circuit. The excitation circuit is electrically connected to the ultrasonic transducer to excite the ultrasonic transducer to generate ultrasonic waves.

9. The vagus nerve stimulation device according to claim 8, characterized in that, The excitation circuit includes a power supply module, a signal generation module, and an amplification module. The signal generation module generates an excitation wave with a set waveform, and the amplification module amplifies the excitation wave and provides it to the ultrasonic transducer to excite the ultrasonic transducer to generate ultrasonic waves.

10. The vagus nerve stimulation device according to claim 9, characterized in that, The excitation circuit also includes a boost circuit module and a matching network module, wherein the matching network module is connected between the amplification module and the ultrasonic transducer.

11. The vagus nerve stimulation device according to any one of claims 1 to 10, characterized in that, The vagus nerve stimulation device is adapted to be placed in the neck so that ultrasound waves can penetrate the skin of the neck and act on the vagus nerve.

12. The vagus nerve stimulation device according to any one of claims 1 to 10, characterized in that, The vagus nerve stimulation device includes a main body adapted to be attached to human skin, and the ultrasound generating unit is disposed on the main body.

13. The vagus nerve stimulation device according to claim 12, characterized in that, The main body is configured as a patch or neckband suitable for attachment to the human neck.

14. The vagus nerve stimulation device according to claim 12, characterized in that, The main body includes a flexible silicone component that can deform to fit human skin.

15. The vagus nerve stimulation device according to any one of claims 1 to 10, characterized in that, The vagus nerve stimulation device has a hierarchical structure.

16. The vagus nerve stimulation device according to claim 15, characterized in that, The hierarchical structure includes a base layer, an ultrasound generating layer, and a coupling layer arranged in sequence.

17. The vagus nerve stimulation device according to any one of claims 1 to 10, characterized in that, The target area includes the vagus nerve region associated with one or more of the following diseases: neuropsychiatric disorders, cognitive impairment, metabolic diseases, inflammatory and autoimmune diseases, cardiovascular diseases, and chronic pain syndromes.

18. The vagus nerve stimulation device according to claim 17, characterized in that, The ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with one or more of the following conditions: major depressive disorder, anxiety disorder, post-traumatic stress disorder, or epilepsy, in order to modulate the excitability and neurotransmitter balance of the central nervous system.

19. The vagus nerve stimulation device according to claim 17, characterized in that, The ultrasound generating unit is configured to controllably deliver ultrasound waves to target areas in the vagus nerve associated with Alzheimer's disease or other neurodegenerative diseases to enhance neural plasticity and promote the secretion of neurotrophic factors.

20. The vagus nerve stimulation device according to claim 17, characterized in that, The ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with obesity or type 2 diabetes, in order to modulate the feeding center in the hypothalamus and improve insulin sensitivity.

21. The vagus nerve stimulation device according to claim 17, characterized in that, The ultrasound generating unit is configured to deliver ultrasound waves in a controlled manner to target areas in the vagus nerve associated with rheumatoid arthritis, Crohn's disease, or sepsis, in order to suppress an overactive inflammatory response and regulate cytokine release.

22. The vagus nerve stimulation device according to claim 17, characterized in that, The ultrasound generating unit is configured to controllably deliver ultrasound waves to a target area in the vagus nerve associated with heart failure and arrhythmia in order to enhance vagal tone of the heart.

23. The vagus nerve stimulation device according to claim 17, characterized in that, The ultrasound generating unit is configured to deliver ultrasound waves in a controlled manner to a target area in the vagus nerve associated with fibromyalgia and migraine, in order to modulate the transmission of pain signals in the central nervous system.

24. The vagus nerve stimulation device according to any one of claims 1 to 10, characterized in that, The ultrasonic generating unit includes multiple ultrasonic transducers arranged in an array.

25. The vagus nerve stimulation device according to claim 24, characterized in that, The ultrasonic transducers consist of four or more units arranged in a rectangular, circular, or ring array.

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