Ultrasound therapy system and use thereof

Abstract

Disclosed in the present invention are an ultrasound therapy system and use thereof. The ultrasound therapy system comprises a main unit and a therapy head. The main unit comprises a signal module, a power supply module, an output module, and a matching module. The therapy head comprises a piezoelectric module and an amplitude transformer module. The length of the piezoelectric module and the length of the amplitude transformer module are half of the wavelength. The frequency range output by the ultrasound therapy system conforms to the frequency range of ultrasonic waves output by bats. According to the present invention, low-frequency and low-intensity ultrasound acts on the immune system of an organism, and specific immune environments such as interferon α high expression, immune strong response, autophagy enhancement, and inflammation level down-regulation are formed in the organism. Therefore, the ultrasound therapy system has the advantages of resisting tumors and viruses, preventing and ameliorating inflammatory aging, prolonging the life span, and treating autoimmune diseases.

Description

Ultrasonic therapy system and its application

[0001] This application claims priority to Chinese patent application PCT / CN2024 / 073058, filed on January 18, 2024. This application incorporates the entire text of the aforementioned Chinese patent application. Technical Field

[0002] The present invention relates to the field of medical equipment, and in particular to an ultrasonic treatment system and applications thereof. Background Art

[0003] Bats carry hundreds of giant viruses, including SARS, rabies, Ebola, and the novel coronavirus. However, their viral loads are relatively small, causing no symptoms, allowing them to coexist with the viruses. Even more surprising is bats' lifespan, which is significantly longer than similar-sized land mammals. The reason for bats' longevity—their ability to control inflammation—may offer new approaches to delaying aging.

[0004] What biological mechanisms make bats so unique that they can withstand a wide range of viruses and ensure their safety? The innate immune response senses cytoplasmic DNA and foreign RNA, responding with upregulation of interferon genes and production of other inflammatory cytokines such as TNF-α. Bats have undergone evolutionary adaptation, weakening their ability to sense cytoplasmic DNA through loss of the PYHIN gene and mutations in regulatory sites within STING.

[0005] In bats, expression of TNF-α and other inflammatory cytokines is reduced, while anti-inflammatory cytokines such as IL-10 are upregulated. Furthermore, activation of the NLRP3 inflammasome is suppressed in bats, leading to reduced production of IL-1β and IL-18 and enhanced RNA sensing. Furthermore, bats constitutively express TNF-α, enhance interferon gene expression, and possess enhanced autophagy. Taken together, these adaptive changes in bats enable them to tolerate viruses while suppressing inflammatory responses.

[0006] Alterations in immunity, leading to increased viral tolerance and reduced inflammation, underlie bats' longevity. Consequences of these changes include a reduction in inflammation-related diseases such as atherosclerosis, arthritis, neurodegeneration, and cancer. Thus, immune changes extend bat lifespan.

[0007] Research on bats reveals that they are one of the few mammals that use ultrasound to locate and prey. Others include naked mole-rats, which also coexist with numerous viruses and are known for their exceptional longevity. Therefore, the ability of bats and naked mole-rats to tolerate viruses, suppress inflammatory responses, and maintain longevity may be related to ultrasound. Summary of the Invention

[0008] In order to solve the technical problem in the prior art of lacking a device that can effectively stimulate the body's immune response, fight tumors, fight viruses, prevent and improve inflammatory aging, prolong life, and treat autoimmune diseases, the present invention provides an ultrasound therapy system and its application.

[0009] In order to solve the above technical problems, the present invention provides a technical solution as follows: an ultrasonic treatment system, which includes a host and a treatment head;

[0010] The host includes the following modules:

[0011] (1) Signal module, generating ultrasonic fundamental frequency signal;

[0012] (2) Power supply module, providing constant DC voltage;

[0013] (3) Output module, amplifying the output of the signal;

[0014] (4) A matching module that matches the output signal with the piezoelectric module of the treatment head to achieve consistency in voltage and current phases;

[0015] The treatment head includes the following modules:

[0016] (i) Piezoelectric module, converting electrical energy into mechanical energy;

[0017] (ii) a horn module for outputting the vibration generated by the piezoelectric module;

[0018] The length of the piezoelectric module and the horn module is half the wavelength;

[0019] The frequency range output by the ultrasonic therapy system is consistent with the frequency range of ultrasonic waves output by bats.

[0020] In a specific embodiment of the present invention, the host further comprises: (5) a display module, through which parameters of ultrasound treatment are set, the parameters including frequency, sound intensity, time and / or duty cycle, and functions of starting and stopping ultrasound treatment are provided;

[0021] The treatment head further includes: (iii) a packaging module: packaging and fixing the piezoelectric module and the horn module therein; and / or,

[0022] The ultrasound treatment system further includes a positioning module for positioning a treatment area.

[0023] In a specific embodiment of the present invention, the ultrasonic wave waveform output by the ultrasonic treatment system is a sine wave, the frequency range of the ultrasonic treatment system output is 20 to 50 kHz, and the output amplitude is 0.1 to 1.6 W / cm2 The pulse width range is 10~1000ms, the period range is 20~2000ms, and the corresponding duty cycle is 1 / 2~1 / 200.

[0024] In a specific embodiment of the present invention, the frequency range of the ultrasonic treatment system output is 30-40 kHz, and the output amplitude is 0.15-0.25 W / cm 2 , the pulse width range is 50~200ms, and the period range is 300~500ms.

[0025] In a specific embodiment of the present invention, the frequency range of the ultrasonic treatment system output is 30-50 kHz, and the output amplitude is 0.15-0.25 W / cm 2 , the pulse width range is 50~200ms, and the period range is 300~400ms.

[0026] In a specific embodiment of the present invention, the ultrasound waves output by the ultrasound treatment system are further processed by a smooth transition algorithm.

[0027] In a specific embodiment of the present invention, the ultrasound treatment system satisfies one or more of the following conditions:

[0028] The display module includes a liquid crystal screen;

[0029] The signal module generates an ultrasonic fundamental frequency signal by means of DDS;

[0030] The output module adopts MOS tube to amplify the output signal;

[0031] The piezoelectric module includes one or more piezoelectric ceramic wafers; and,

[0032] The positioning module is a B-ultrasound probe, preferably a miniature B-ultrasound probe.

[0033] In a specific embodiment of the present invention, the positioning module is fixed to one side of the treatment head, and the two are located in the same plane and form an angle of 0° to 90°, so that the sound channel of the therapeutic ultrasound is displayed on the B-ultrasound image.

[0034] In a specific embodiment of the present invention, the angle is 10° to 80°, preferably 30° to 60°.

[0035] In a specific embodiment of the present invention, the piezoelectric module satisfies one or more of the following conditions:

[0036] The piezoelectric module includes four piezoelectric ceramic chips;

[0037] The piezoelectric ceramic wafer is a P42 piezoelectric ceramic; and,

[0038] The piezoelectric ceramic chips are arranged alternately according to positive and negative poles.

[0039] In a specific embodiment of the present invention, the packaging module includes: a front cover plate, a rear cover plate, an outer shell and a fixing member, and the density of the material of the rear cover plate is greater than the density of the material of the front cover plate.

[0040] In a specific embodiment of the present invention, the packaging module satisfies one or more of the following conditions:

[0041] The front cover is made of aluminum alloy;

[0042] The rear cover is made of stainless steel;

[0043] The housing is convenient for holding and is preferably cylindrical; and,

[0044] The fixing member is a set screw, which fastens and connects the modules; the set screw preferably has prestress.

[0045] In a specific embodiment of the present invention, the shape of the horn module is rectangular, circular, spherical, honeycomb, needle-shaped or ball-head.

[0046] In a specific embodiment of the present invention, the horn module satisfies one or more of the following conditions:

[0047] The output surface of the horn module is wrapped with a silicone rubber film;

[0048] The horn module uses a tangent circular surface transition to process the coarse and fine transition position; and,

[0049] The horn module further comprises a flange for mounting the housing; preferably, the flange is located at a node point.

[0050] In a specific embodiment of the present invention, the ultrasound therapy system is used to regulate the following changes in the body:

[0051] (1) increasing the expression of interferons and / or interleukins; the interferons include IFN-α, IFN-β and IFN-γ, and the interleukins include IL-10 and IL-15;

[0052] (2) Promote the proliferation of CD4+ T and / or CD40+ immune cells, and / or reduce the ratio of CD8 / CD4.

[0053] To solve the above technical problems, the present invention provides a technical solution: a method for stimulating an immune response in an organism using the ultrasound therapy system of the present invention, wherein ultrasound stimulation is performed on a target immune organ, preferably an immune organ such as the spleen or the brain, comprising the following steps:

[0054] (1) placing the ultrasound treatment system close to or in contact with a target point;

[0055] (2) adjusting parameters so that the ultrasonic treatment system generates and transmits ultrasonic waves;

[0056] (3) According to the location and area of ​​the target, adjust the ultrasonic transmission direction, output frequency, amplitude, pulse width, cycle and output time.

[0057] In a specific embodiment of the present invention, the stimulation of the body's immune response is anti-tumor, anti-viral, prevention and improvement of inflammatory aging, extension of life and / or treatment of autoimmune diseases.

[0058] In a specific embodiment of the present invention, the frequency range of the ultrasonic treatment system output is 20-50 kHz, and the output amplitude is 0.1-1.6 W / cm 2 The pulse width ranges from 10 to 1000 ms, the period ranges from 20 to 2000 ms, and the corresponding duty cycle ranges from 1 / 2 to 1 / 200; and the time range of ultrasonic stimulation is from 60 to 600 s.

[0059] In a specific embodiment of the present invention, the frequency range of the ultrasonic treatment system output is 30-40 kHz, and the output amplitude is 0.15-0.25 W / cm 2 The pulse width ranges from 50 to 200 ms, the period ranges from 300 to 500 ms, and the corresponding duty cycle ranges from 1 / 2 to 1 / 200; and the time range of ultrasonic stimulation is from 120 to 240 s.

[0060] In a specific embodiment of the present invention, the frequency range of the ultrasonic treatment system output is 30-50 kHz, and the output amplitude is 0.15-0.25 W / cm 2 The pulse width ranges from 50 to 200 ms, the period ranges from 300 to 400 ms, and the corresponding duty cycle ranges from 1 / 2 to 1 / 200; and the time range of ultrasonic stimulation is from 120 to 240 s.

[0061] In a specific embodiment of the present invention, the frequency of the ultrasound treatment system output is 33kHz, and the amplitude of the output is 0.2W / cm 2 , the range of pulse width is 100 ms, the range of cycle is 400 ms, and the time range of ultrasound stimulation is 180 s.

[0062] In a specific embodiment of the present invention, the frequency of the ultrasound treatment system output is 50kHz, and the amplitude of the output is 0.2W / cm 2 , the range of pulse width is 100 ms, the range of cycle is 400 ms, and the time range of ultrasound stimulation is 180 s.

[0063] In a specific embodiment of the present invention, the target point is subjected to ultrasonic stimulation when the body has developed a tumor, been infected with a virus, has developed inflammation, has aged, or has an autoimmune disease.

[0064] In order to solve the above technical problems, the present invention provides a technical solution: application of the ultrasonic treatment system according to the present invention in the preparation of a device for stimulating the body's immune response.

[0065] In a specific embodiment of the present invention, the stimulation of the body's immune response is anti-tumor, anti-viral, prevention and improvement of inflammatory aging, extension of life and / or treatment of autoimmune diseases.

[0066] In order to solve the above technical problems, the present invention provides a technical solution: the ultrasound treatment system as described in the present invention is used to stimulate the body's immune response.

[0067] In a specific embodiment of the present invention, the stimulation of the body's immune response is anti-tumor, anti-viral, prevention and improvement of inflammatory aging, extension of life and / or treatment of autoimmune diseases.

[0068] On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0069] The reagents and raw materials used in the present invention are commercially available.

[0070] The positive progress effect of the present invention is:

[0071] This invention uses low-frequency, low-intensity ultrasound to target the immune system, creating a specific immune environment that results in high interferon-α expression, a strong immune response, enhanced autophagy, and reduced inflammation. This has the potential to fight tumors, fight viruses, prevent and improve inflammatory aging, prolong life, and treat autoimmune diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0072] Figure 1 is a schematic diagram of the host module.

[0073] FIG2 is a schematic diagram of a piezoelectric ceramic wafer with alternating positive and negative electrodes.

[0074] FIG3 is a schematic diagram of the structure of a horn tool head with a rectangular or spherical output surface.

[0075] FIG4 is a schematic diagram of the structure of a horn tool head with a rectangular output surface.

[0076] FIG5 is a schematic diagram of the structure of a horn tool head with a spherical output surface.

[0077] Figure 6 is a schematic diagram of the mounting structure of the horn tool head housing.

[0078] Figure 7 shows the structure of the treatment head.

[0079] Figure 8 shows the piezoelectric ceramic structure.

[0080] Figure 9 shows the structure of the horn tool head.

[0081] FIG10 is a schematic diagram of a sine wave.

[0082] FIG11 is a schematic diagram of sinusoidal wave modulation.

[0083] FIG12 is a schematic diagram of the output ultrasonic wave processed by the smooth transition algorithm.

[0084] FIG13 is a diagram showing the installation method of the positioning module and the treatment head.

[0085] FIG14 is a schematic diagram of therapeutic ultrasound and therapeutic organs on an image of a positioning module.

[0086] Figure 15 shows the tumor size and growth curve.

[0087] Figure 16 shows the pathological analysis of the tumor.

[0088] FIG17 shows the statistics and analysis of mouse blood cytokines.

[0089] FIG18 shows the statistics and analysis of immune cells in mouse blood.

[0090] FIG19 shows the statistics and analysis of cytokines in rat blood. DETAILED DESCRIPTION

[0091] The technical solution proposed by the present invention is to use ultrasound to stimulate the body's immune effect.

[0092] Ultrasound stimulation alters the body's immune system, triggering a series of immune responses, including increased interferon alpha expression, viral tolerance, and enhanced inflammation control. Based on bats' ability to transmit ultrasound and other related physiological characteristics, the inventors developed a specialized ultrasound therapy system.

[0093] The main parameters of the instrument are as follows:

[0094] Frequency: 20KHz~50KHz

[0095] Sound intensity: 0.1-1.6W / cm 2

[0096] The main evaluation indicators are as follows:

[0097] Interferon α, interferon β, interferon γ, CD4+ T cells, CD8+ T cells, TNF-α, IL-10, IL-1β, IL-15, IL-18

[0098] The main immune effects of this instrument can be used in the following aspects:

[0099] Anti-tumor

[0100] Antiviral

[0101] ●Prevent and improve inflammatory aging and prolong life

[0102] Treating autoimmune diseases

[0103] The inventors designed relevant animal experiments, using ultrasound to stimulate the body and verify its immune effect.

[0104] Experiment 1 designed a mouse liver tumor model. After more than a year of animal experiments and repeated optimization of technical parameters, the treatment group showed a 42% increase in interferon α, 35% increase in interferon β, 34% increase in interferon γ, a 72% increase in CD4+ T cells, and a 42% increase in IL-15 compared to the control group. Tumor cell growth was also suppressed. These experiments demonstrate that ultrasound stimulates the immune system, leading to the production of interferon and the increase in other beneficial immune factors and cells, thereby inhibiting tumor cells.

[0105] Experiment 2 designed a normal mouse model. After a series of animal experiments, the treatment group showed decreased TNF-α expression, increased anti-inflammatory cytokine IL-10, and decreased pro-inflammatory cytokines IL-1β and IL-18 compared to the control group. These changes may help control inflammation, delay aging, and treat autoimmune diseases.

[0106] Experiment 3 designed a model of 12-month-old rats. Animal experiments showed that the anti-inflammatory cytokine IL-10 increased by 68% in the treatment group compared to the control group. This can help control inflammation, delay aging, and treat autoimmune diseases.

[0107] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0108] Example 1 Ultrasound therapy system

[0109] The ultrasonic treatment system of the present invention consists of a main unit and a treatment head.

[0110] The host part includes the following modules (the schematic diagram is shown in Figure 1):

[0111] Display module: It is mainly composed of an LCD screen. Human-computer interaction is achieved through the LCD screen. The parameters of ultrasound treatment can be set through the LCD screen, including frequency, sound intensity, time, duty cycle, etc., and the function of starting and stopping ultrasound treatment is provided.

[0112] Signal module: Generates ultrasonic fundamental frequency signal through DDS. The main control unit generates the electrical signal that drives the ultrasound based on parameters such as frequency, sound intensity, time, and duty cycle.

[0113] Power supply module: It is mainly responsible for converting AC power into DC voltage and providing constant DC voltage for various components.

[0114] Output module: uses MOS tube to amplify the output signal.

[0115] Matching module: matches the output electrical signal with the transducer to achieve consistency in voltage and current phase.

[0116] The treatment head is mainly generated by the piezoelectric vibrator, which is then output through the tool head. Both the piezoelectric vibrator and the tool head are designed to be half the wavelength. It includes the following modules:

[0117] Piezoelectric ceramics: Piezoelectric ceramic chips are components that convert electrical energy into mechanical energy and are the core components of ultrasonic therapy systems. This device's piezoelectric ceramics utilize four annular ceramic chips made of P42 material. P42 piezoelectric ceramics have high acoustic-to-electricity conversion efficiency and are suitable for immunotherapy. The number of these four annular piezoelectric ceramic chips is calculated based on the required acoustic power. Too few chips will produce too little power and fail to achieve the desired immunotherapy effect. Increasing the thickness of each chip increases the difficulty of manufacturing the piezoelectric chip, hindering immunotherapy. Piezoelectric chips have positive and negative poles, and the four chips need to be arranged alternately during installation, as shown in Figure 2.

[0118] The horn tool head can be designed in various shapes depending on the treatment needs. For example, a rectangular shape can be used for spleen treatment. Alternatively, a spherical design can be used to enhance transducer focus, as shown in Figure 3. The structure of a horn tool head with a rectangular output surface is shown in Figure 4; the structure of a spherical output surface is shown in Figure 5.

[0119] The horn tool head can be replaced to suit different output waveform requirements. For example, it can be designed into honeycomb, needle, ball head, etc. Note that the design of the horn needs to meet the theoretical requirements of half wavelength.

[0120] The output surface of a conventional horn tool head uses metal to directly contact the skin, which is not conducive to immunotherapy. This solution adds a thin layer of silicone rubber to the output surface, which prevents direct metal contact with the skin and also facilitates ultrasonic coupling, while preventing the thermal effects of ultrasound from being directly transmitted to the human skin.

[0121] The thick and thin transition of the horn tool head adopts a tangent circular surface transition method, which makes the transmission efficiency of ultrasound on the horn higher.

[0122] The horn tool head also has a flange for mounting the housing. The flange is located at the node point to minimize the impact on the transducer vibration. A schematic diagram is shown in Figure 6.

[0123] Front cover: Made of aluminum alloy.

[0124] Rear cover: Made of stainless steel.

[0125] Housing: Designed in cylindrical shape, convenient for handheld operation.

[0126] Set screws: These fasten the modules together. These screws must have a certain amount of prestress within a certain range. Double-stacked self-locking washers or disc washers are recommended; C-shaped washers are generally not recommended to prevent loosening during use. Use a torque wrench to ensure the torque is within the prestress range.

[0127] The treatment head of the present invention (structure shown in FIG7 ) generates ultrasonic waves after the piezoelectric ceramic is energized. Due to the high density of the stainless steel of the rear cover (about 7.9 g / cm 3 ), while the front cover aluminum alloy has a low density (about 2.8g / cm 3 ), resulting in a large displacement amplitude of the forward-directed ultrasonic output. The amplitude of the output ultrasonic waves is further increased by the front horn tool head, resulting in the treatment head of the present invention featuring high output efficiency and focused ultrasound. Furthermore, the tool head is designed to correspond in size to the treatment area, ensuring that the entire treatment head meets the requirements of immunotherapy.

[0128] Piezoelectric ceramics (structure shown in Figure 8) possess not only piezoelectricity but also dielectric and elastic properties. They are widely used in medical imaging, acoustic sensors, acoustic transducers, ultrasonic motors, and other applications. Piezoelectric ceramics are manufactured using the piezoelectric effect, a process in which mechanical stress causes the relative displacement of internal positive and negative charge centers within the material, leading to polarization. This results in bound charges of opposite sign forming on the surfaces of the material at both ends, giving them a sensitive characteristic.

[0129] The output surface of the horn tool head (structure shown in FIG9 ) is an elongated rectangle, which is designed to a corresponding size according to the shape of the treatment area so that the entire treatment head meets the needs of immunotherapy.

[0130] The ultrasonic waveform output by this device is a pulse-modulated sine wave. The schematic diagram of the sine wave is shown in Figure 10. In Figure 10, the horizontal axis is time and the vertical axis is the output amplitude. The frequency range of the output of this device is 20 to 50 kHz, and the output amplitude, that is, the ultrasonic sound intensity range is 0.1 to 1.6 W / cm 2The schematic diagram of sinusoidal wave modulation is shown in Figure 11. The duration of transmission in the modulated waveform is the pulse width, the period from one transmission start point to the next is the cycle, and the pulse width divided by the cycle is the duty cycle. The pulse width of this device ranges from 10 to 1000 ms, and the cycle ranges from 20 to 2000 ms, corresponding to a duty cycle of 1 / 2 to 1 / 200. The total treatment time of this device ranges from 60 to 600 s. The ultrasound output of this device also undergoes a smooth transition algorithm, as shown in Figure 12. Each pulse output gradually increases in amplitude, reaching a stable pulse width after reaching the output amplitude. At the end of the pulse, the amplitude also gradually decreases. This output method is more comfortable and more tolerable for patients, while also making the device more stable and less prone to damage. It also better aligns with the characteristics of bat ultrasound output, making the device more realistic. Parameters such as the ultrasound output amplitude and duty cycle can be edited to generate treatment sequences based on treatment needs, making the device more intelligent and user-friendly. If new characteristics of bat ultrasound output are discovered later, the treatment sequence can be modified to continue the bionic design.

[0131] ●The positioning module is used to locate the treatment area and is an optional module. When precise positioning is required, a micro B-ultrasound probe can be used, generally a micro B-ultrasound probe is used. The B-ultrasound probe and the B-ultrasound host work together to detect the internal organs and tissues of the human body. By fixing the probe of the positioning module and the treatment head of the present invention together, the internal organs of the human body can be seen on the image of the positioning module, and the sound channel of the ultrasound treatment can also be determined according to the positional relationship. According to the treatment needs, the appropriate treatment sound channel and the appropriate treatment organ are selected for immunotherapy. The installation method of the positioning module and the treatment head is shown in Figure 13. The schematic diagram of the treatment ultrasound and treatment organs on the image of the positioning module is shown in Figure 14.

[0132] Example 2 Anti-tumor verification of ultrasound therapy system

[0133] The mouse liver tumor model was used to verify that low-frequency, low-intensity ultrasound acts on the body's immune system, stimulating the body's immune response, thereby inhibiting viruses and having anti-tumor effects. The experimental groups are shown in Table 1.

[0134] Table 1 Experimental groups

[0135] Note: All experimental mice were inoculated with tumors at the same time, and samples were taken for testing and treatment at the same time. 3 Or if the longest diameter of the tumor is greater than 15 mm, the experiment will be terminated.

[0136] Treatment area:

[0137] Spleens of treated mice

[0138] Treatment:

[0139] Using a specialized ultrasound therapy system developed by the present invention, ultrasound therapy was performed on the spleens of experimental mice. The tool head used in this experiment was rectangular, suitable for spleen treatment. Before the experiment, the mice were skin-prepared, and ultrasound was used to locate the treatment site (the spleen) on their skin. The mice were anesthetized and then treated.

[0140] Treatment parameters:

[0141] Ultrasonic frequency: 33kHz

[0142] Ultrasonic sound intensity: 0.2W / cm 2

[0143] Treatment time: 180 seconds

[0144] ●Modulation pulse width: 100ms

[0145] ●Modulation period: 400ms

[0146] Index detection

[0147] 1. After the experiment, take pictures of the tumor tissue and observe the pathology by HE.

[0148] 2. Interferon IFN-α, IFN-β, IFN-γ, IL-15 in serum;

[0149] 3. Flow cytometry detection of CD4+T cells, CD8+T cells, CD8 / CD4 T cell ratio, and CD40+ immune cells in the blood.

[0150] Experimental results

[0151] 1. Relationship between tumor size and ultrasound therapy

[0152] As shown in Figure 15, the overall tumor volume is C>A>B. Compared with the normal model control group C, the tumor growth of the experimental A (stimulation treatment first, then modeling) group was inhibited, but the inhibitory effect was not obvious and had no statistical significance; the tumor growth of the experimental B (modeling first, then stimulation treatment) group was significantly inhibited, and P≤0.05 was statistically significant.

[0153] 2. Pathological Analysis of Tumors

[0154] As shown in Figure 16, the tumor necrosis area is A>B>C. Compared with the normal model control group C, the necrosis rate of tumor cells in the experimental A (stimulation treatment before modeling) group and the experimental B (modeling before stimulation treatment) group was significantly increased, and the necrosis rate of tumor cells in the experimental A group was higher than that in the experimental B group. However, there was no significant statistical difference between the groups.

[0155] 3. Relationship between cytokines and ultrasound therapy

[0156] Table 2 Statistics and analysis of mouse blood cytokines Note: a: p<0.05Vs C; b: p<0.01Vs C;

[0157] Experimental results: Cytokines in mouse blood were detected by ELISA (Table 2 and Figure 17):

[0158] No. 1: The IFN-α content in the blood of mice in experimental groups A, B, and C was B>A>C, which were 106.73±28.6pg / ml, 128.69±20.72pg / ml, and 90.46±20.83pg / ml, respectively; compared with the normal model control group C, the IFN-α content in the blood of mice in experimental group A increased, but there was no statistical significance. The IFN-α content in the blood of mice in experimental group B increased significantly, and P≤0.01 was statistically significant.

[0159] No. 2: The IFN-β content in the blood of mice in experimental groups A, B, and C was B>A>C, which were 213.80±69.89pg / ml, 258.28±61.04pg / ml, and 190.59±43.73pg / ml, respectively; compared with the normal model control group C, the IFN-β content in the blood of mice in experimental group A increased slightly, but there was no statistical significance. The IFN-β content in the blood of mice in experimental group B increased significantly, and P≤0.05 was statistically significant.

[0160] No. 3: The IFN-γ content in the blood of mice in experimental groups A, B, and C was B>A>C, which were 97.11±32.28pg / ml, 110.54±22.93pg / ml, and 82.13±11.98pg / ml, respectively; compared with the normal model control group C, the IFN-γ content in the blood of mice in experimental group A increased slightly, but there was no statistical significance, while the IFN-γ content in the blood of mice in experimental group B increased significantly, with P≤0.05 being statistically significant.

[0161] No. 4: The IL-5 content in the blood of mice in experimental groups A, B, and C was B>A>C, which were 97.11±32.28pg / ml, 110.54±22.93pg / ml, and 82.13±11.98pg / ml, respectively; compared with the normal model control group C, the IL-5 content in the blood of mice in experimental groups A and B was significantly increased, P≤0.05 was statistically significant, and the IL-5 content in experimental group B was higher than that in experimental group A.

[0162] 4. Relationship between immune cells and ultrasound therapy

[0163] Table 3 Statistics and analysis of immune cells in mouse blood Note: a: p<0.05Vs C; b: p<0.01Vs C;

[0164] Experimental results: The proportion of immune cells in mouse blood was detected by flow cytometry (Table 3 and Figure 18):

[0165] No. 1: The ratio of CD4+T cells in the blood of mice in experimental groups A, B, and C was B>A>C, which were 20.48±8.05, 26.41±5.45, and 15.31±9.08, respectively; compared with the normal model control group C, the ratio of CD4+T cells in the blood of mice in experimental group A increased, but there was no statistical significance. The ratio of CD4+T cells in the blood of mice in experimental group B increased significantly, and P≤0.05 was statistically significant.

[0166] No. 2: There was no significant difference in the content of CD8+T cells in the blood of mice in experimental groups A, B, and C, which were 8.54±2.97, 8.43±2.79, and 8.73±2.12, respectively; compared with the normal model control group C, the proportion of CD8+T cells in the blood of mice in experimental groups A and B did not change.

[0167] No. 3: The ratio of CD40+ immune cells in the blood of mice in experimental groups A, B, and C was A>B>C, which were 30.68±4.67, 28.91±7.92, and 25.13±5.13, respectively; compared with the normal model control group C, the ratio of CD40+ immune cells in the blood of mice in experimental groups A and B increased slightly, but there was no statistical significance.

[0168] No. 4: The CD8 / CD4 T cell ratios in the blood of mice in experimental groups A, B, and C were C>A>B, which were 44.03±14.35, 32.66±10.31, and 72.78±41.28, respectively; compared with the normal model control group C, the CD8 / CD4 cell ratios in the blood of mice in experimental groups A and B were significantly decreased, with P≤0.05 being statistically significant, and the CD8 / CD4 cell ratios in experimental group B were lower than those in experimental group A.

[0169] Example 3: Verification of Ultrasound Therapy System for Preventing and Improving Inflammatory Aging

[0170] A 12-month-old rat model was designed to demonstrate that low-frequency, low-intensity ultrasound stimulates the immune system, thereby preventing and improving inflammatory aging, extending lifespan, and / or treating autoimmune diseases. The experimental groups are shown in Table 4.

[0171] Table 4 Experimental groups

[0172] Treatment area:

[0173] Treating the spleen in rats

[0174] Treatment:

[0175] Using the dedicated ultrasound therapy system developed by this invention, experimental rats underwent ultrasound therapy on their spleens. The tool head used in this experiment was rectangular, suitable for spleen treatment. Before the experiment, the rats were skin-prepared, and ultrasound was used to locate the treatment site (the spleen) on their body surfaces. The rats were anesthetized and then treated.

[0176] Treatment parameters:

[0177] Ultrasonic frequency: 50kHz

[0178] Ultrasonic sound intensity: 0.2W / cm 2

[0179] Treatment time: 180 seconds

[0180] ●Modulation pulse width: 100ms

[0181] ●Modulation period: 400ms

[0182] Index detection

[0183] ●After the experiment, IL-10 was detected in the rat serum;

[0184] Experimental results

[0185] The relationship between IL-10 and ultrasound therapy

[0186] Table 5 Statistics and analysis of IL-10 in rat blood Note: a: p < 0.01 Vs B;

[0187] Experimental results: Cytokines in rat blood were detected by ELISA (Table 5 and Figure 19):

[0188] No. 1: The IL-10 content in the blood of rats in experimental groups A and B was A>B, which were 405.01±60.89pg / ml and 241.22±63.95pg / ml respectively; compared with the control group B, the IL-10 content in the blood of rats in experimental group A was significantly increased, P≤0.01 was statistically significant.

[0189] IL-10 plays an important role in anti-inflammation and immune regulation, and is closely related to inflammatory aging. Maintaining the level and function of IL-10 can help slow down the process of inflammatory aging and thus prolong life.

[0190] Although the above describes specific embodiments of the present invention, it should be understood by those skilled in the art that these are merely illustrative and that various changes or modifications may be made to these embodiments without departing from the principles and essence of the present invention. Therefore, the scope of protection of the present invention is defined by the appended claims.

Claims

1. An ultrasonic therapy system, which includes a main unit and a treatment head; characterized in that, the main unit includes the following modules: (1) A signal module, which generates a fundamental frequency signal of ultrasound; (2) A power supply module, which provides a constant DC voltage; (3) An output module, which amplifies the output of the signal; (4) A matching module, which matches the output signal with the piezoelectric module of the treatment head to achieve consistency in voltage, current, and phase; the treatment head includes the following modules: (i) A piezoelectric module, which converts electrical energy into mechanical energy; (ii) A horn module, which outputs the vibration generated by the piezoelectric module; the lengths of the piezoelectric module and the horn module are half of the wavelength; the frequency range output by the ultrasonic therapy system conforms to the frequency range of the ultrasonic waves output by bats.

2. The ultrasonic therapy system according to claim 1, characterized in that, the main unit further includes: (5) A display module, through which the parameters of ultrasonic therapy are set. The parameters include frequency, sound intensity, time, and / or duty cycle, and provide the functions of starting and aborting ultrasonic therapy; the treatment head further includes: (iii) A packaging module: encapsulating and fixing the piezoelectric module and the horn module therein; and / or, the ultrasonic therapy system further includes a positioning module for positioning the treatment area.

3. The ultrasonic treatment system according to claim 1, characterized in that The ultrasonic waveform output by the ultrasonic treatment system is a sine wave, the frequency range output by the ultrasonic treatment system is 20-50 kHz, and the output amplitude is 0.1-1.6 W / cm 2 , the pulse width range is 10-1000 ms, the cycle range is 20-2000 ms, and the corresponding duty cycle is 1 / 2-1 / 200; Preferably, the frequency range output by the ultrasonic treatment system is 30 - 40 kHz, the output amplitude is 0.15 - 0.25 W / cm 2 , the pulse width range is 50 - 200 ms, and the period range is 300 - 500 ms; or, the frequency range output by the ultrasonic treatment system is 30 - 50 kHz, the output amplitude is 0.15 - 0.25 W / cm 2 , the pulse width range is 50 - 200 ms, and the period range is 300 - 400 ms; Preferably, the ultrasonic waves output by the ultrasonic therapy system are also processed by an algorithm with smooth transition.

4. The ultrasonic treatment system according to claim 2, wherein The ultrasonic therapy system satisfies one or more of the following conditions: the display module includes a liquid crystal screen; the signal module generates a fundamental frequency signal of ultrasound by means of DDS; the output module uses MOS transistors to amplify the output of the signal; the piezoelectric module includes one or more piezoelectric ceramic wafers; and, the positioning module is a B-ultrasound probe, preferably a micro B-ultrasound probe; Preferably, the positioning module is fixed on one side of the treatment head, and the two are in the same plane and form an angle of 0° to 90°, so that the sound channel of the therapeutic ultrasound is shown in the B-ultrasound image; More preferably, the degree of the angle is 10° to 80°, preferably 30° to 60°.

5. The ultrasonic treatment system according to claim 1, characterized in that, The piezoelectric module satisfies one or more of the following conditions: the piezoelectric module includes 4 piezoelectric ceramic wafers; the piezoelectric ceramic wafers are P42 piezoelectric ceramics; and, the piezoelectric ceramic wafers are arranged alternately with positive and negative polarities.

6. The ultrasonic treatment system according to claim 2, wherein The packaging module includes: a front cover plate, a rear cover plate, a housing, and a fixing member. The density of the material of the rear cover plate is greater than that of the material of the front cover plate; preferably, the packaging module satisfies one or more of the following conditions: the front cover plate is made of aluminum alloy; the rear cover plate is made of stainless steel; the housing is convenient for holding, preferably cylindrical; and, the fixing member is a set screw for tightly connecting each module; the set screw preferably has prestress.

7. The ultrasonic treatment system according to claim 1, characterized in that, The shape of the horn module is rectangular, circular, spherical, honeycomb-shaped, needle-shaped, or ball-headed; preferably, the horn module satisfies one or more of the following conditions: the output surface of the horn module is wrapped with a silicone rubber film; the horn module uses a tangential circular surface to transition and process the thick-thin transition position; and, The horn module further includes a flange for mounting the housing; preferably, the position of the flange is at the position of the wave node.

8. The ultrasonic treatment system according to any one of claims 1-7, characterized in that, It is used to adjust the following changes in the body: (1) Increase the expression of interferon and / or interleukin; the interferon includes IFN-α, IFN-β, and IFN-γ, and the interleukin includes IL-10 and IL-15; (2) Promote the proliferation of CD4+T and / or CD40+ immune cells, and / or reduce CD8 / CD4.

9. A method for stimulating the body's immune response using the ultrasonic treatment system according to any one of claims 1-8, wherein, Performing ultrasound stimulation on a target target, preferably an immune organ such as the spleen or the brain, includes the following steps: (1) Bring the ultrasound treatment system close to or into contact with the target target; (2) Adjust the parameters to cause the ultrasound treatment system to generate and emit ultrasonic waves; (3) According to the position and area of the target target, adjust the conduction direction, output frequency, amplitude, pulse width, period, and output time of the ultrasonic waves; Preferably, the stimulation of the body's immune response is for anti-tumor, anti-viral, preventing and improving inflammatory aging, extending lifespan, and / or treating autoimmune diseases.

10. The method according to claim 9, wherein The frequency range output by the ultrasonic treatment system is 20 - 50 kHz, and the output amplitude is 0.1 - 1.6 W / cm 2 , the pulse width range is 10 - 1000 ms, the cycle range is 20 - 2000 ms, and the corresponding duty cycle is 1 / 2 - 1 / 200; and the ultrasonic stimulation time range is 60 - 600 s.

11. The method according to claim 9 or 10, characterized in that, The frequency range output by the ultrasonic treatment system is 30 - 40 kHz, and the output amplitude is 0.15 - 0.25 W / cm 2 , the pulse width ranges from 50 - 200 ms, the period ranges from 300 - 500 ms, and the corresponding duty cycle is 1 / 2 - 1 / 200; and the time range of ultrasonic stimulation is 120 - 240 s; or, the frequency range output by the ultrasonic treatment system is 30 - 50 kHz, and the output amplitude is 0.15 - 0.25 W / cm 2 , the pulse width ranges from 50 - 200 ms, the period ranges from 300 - 400 ms, and the corresponding duty cycle is 1 / 2 - 1 / 200; and the time range of ultrasonic stimulation is 120 - 240 s.

12. The method according to claim 11, wherein The frequency output by the ultrasonic treatment system is 33 kHz, and the output amplitude is 0.2 W / cm 2 , the pulse width ranges from 100 ms, the cycle range is 400 ms, and the ultrasonic stimulation time range is 180 s; or, the frequency output by the ultrasonic treatment system is 50 kHz, and the output amplitude is 0.2 W / cm 2 , the pulse width ranges from 100 ms, the cycle range is 400 ms, and the ultrasonic stimulation time range is 180 s.

13. The method according to any one of claims 9 to 12, characterized in that, The time for performing ultrasound stimulation on the target target is when the body has developed a tumor, been infected with a virus, developed inflammation, aged, or has an autoimmune disease.

14. Use of the ultrasound treatment system according to any one of claims 1-8 in the preparation of a device for stimulating the body's immune response; Preferably, the stimulation of the body's immune response is for anti-tumor, anti-viral, preventing and improving inflammatory aging, extending lifespan, and / or treating autoimmune diseases.

15. The ultrasound treatment system according to any one of claims 1-8, which is used to stimulate the body's immune response; Preferably, the stimulation of the body's immune response is for anti-tumor, anti-viral, preventing and improving inflammatory aging, extending lifespan, and / or treating autoimmune diseases.

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