Ultrasonic device and system

Abstract

This ultrasonic device comprises: a means for generating a drive signal for driving an ultrasonic transducer that emits ultrasonic waves; and a means for projecting ultrasonic waves based on the drive signal onto the skin of a subject at a vaccine vaccination position, and thereby promoting, in the subject, the production of antibodies by the vaccine.

Description

Ultrasonic device and system

[0001] The present disclosure relates to an ultrasonic device and a system.

[0002] An adjuvant is a substance administered together with a vaccine and is used to enhance the effect of vaccination. By using an adjuvant when inoculating a vaccine that is not sufficiently effective on its own, such as a vaccine that purifies and inoculates some components of an antigen, it is possible to achieve both the efficacy and safety of the vaccine.

[0003] Patent Document 1 discloses a composition containing a universal influenza vaccine antigen and a vaccine adjuvant.

[0004] Reexamination Bulletin No. 2020-02227

[0005] As new immunotherapies are being researched and developed, new approaches for enhancing the efficacy of vaccines are expected.

[0006] An object of the present invention is to provide a technique capable of enhancing the effect of a vaccine using ultrasonic waves.

[0007] An ultrasonic device according to an aspect of the present invention includes means for generating a drive signal for driving an ultrasonic transducer that emits ultrasonic waves, and means for irradiating ultrasonic waves based on the drive signal to the skin at the vaccination position of the vaccine in the subject, thereby promoting the production of antibodies by the vaccine in the subject.

[0008] Schematic diagram showing the configuration of the ultrasonic device. Block diagram showing the functional configuration of the control unit. Diagram illustrating the configuration of the ultrasonic radiation unit. Diagram explaining the state where the ultrasonic waves radiated from the ultrasonic radiation unit are focused. Flowchart showing an operation example of the ultrasonic device. Diagram explaining the implementation timing of vaccination, ultrasonic irradiation, and serum collection in the example. Diagram showing the analysis results in the example. Flowchart showing an operation example of the ultrasonic device. Schematic diagram showing the configuration of the ultrasonic device. Block diagram showing the functional configuration of the control unit. Flowchart showing an operation example of the ultrasonic device. Schematic diagram showing the configuration of the system.

[0009] Hereinafter, one embodiment of the present invention will be described in detail with reference to the drawings. In the drawings used to illustrate the embodiment, the same reference numerals are generally used for identical components, and repeated descriptions thereof will be omitted.

[0010] (1) Configuration of the ultrasonic device The configuration of the ultrasonic device of this embodiment will be described below. Figure 1 is a schematic diagram showing the configuration of the ultrasonic device of this embodiment.

[0011] As shown in Figure 1, the ultrasonic device 1 comprises a control unit 11 and an ultrasonic emission unit 15. The control unit 11 and the ultrasonic emission unit 15 are connected by wire or wireless.

[0012] The control unit 11 controls the ultrasonic emission unit 15. Specifically, the control unit 11 generates a drive signal to drive the ultrasonic transducer 14 of the ultrasonic emission unit 15 and outputs it to the ultrasonic emission unit 15.

[0013] The ultrasonic emission unit 15 has an ultrasonic transducer 14 that emits ultrasonic waves, and irradiates the skin 10 at the vaccine injection site on the target with ultrasonic waves based on a drive signal input from the control unit 11, thereby promoting antibody production by the vaccine in the target. The target to be irradiated with ultrasonic waves and vaccinated is a human or a non-human animal (for example, a mammal, fish, bird, amphibian, or reptile). In this embodiment, "injection site" refers to a location on the target's body that includes the place where the vaccine was administered and its vicinity. For example, when the vaccine is administered to the target by injection, the injection site is the location on the target's body where the syringe needle was inserted.

[0014] (1-1) Configuration of the Control Unit The configuration of the control unit of this embodiment will be described. Figure 2 is a block diagram showing the functional configuration of the control unit of this embodiment.

[0015] As shown in Figure 2, the control unit 11 includes a storage device 111, a processor 112, an input / output interface 113, a communication interface 114, an operation unit 116, and a display unit 117.

[0016] The storage device 111 is configured to store programs and data. The storage device 111 is, for example, a combination of ROM (Read Only Memory), RAM (Random Access Memory), and storage (e.g., flash memory or hard disk).

[0017] The program includes, for example, the following: • Operating System (OS) program • Application program for executing information processing (e.g., driver application for controlling the ultrasonic radiation unit 15)

[0018] The data includes, for example, at least one of the following: • A database referenced in information processing • Data obtained by performing information processing (i.e., the results of information processing)

[0019] The processor 112 is a computer that realizes the functions of the control unit 11 by starting a program stored in the storage device 111. The processor 112 is, for example, at least one of the following: • CPU (Central Processing Unit) • GPU (Graphic Processing Unit) • ASIC (Application Specific Integrated Circuit) • FPGA (Field Programmable Array)

[0020] The input / output interface 113 is configured to receive instructions from the user (for example, a medical professional using the ultrasound device 1 or a person receiving vaccination) from the operation unit 116 and to output information to the display unit 117.

[0021] The drive circuit 115 is configured to generate a drive signal to drive the ultrasonic transducer 14 and output the drive signal to the ultrasonic radiation unit 15, in accordance with the control of the processor 112.

[0022] The operation unit 116 is configured to receive user input to the control unit 11. The operation unit 116 may be, for example, a switch, a button, a keyboard, a pointing device, a touch panel, or a combination thereof.

[0023] The display unit 117 is configured to display an image generated by the control unit 11. The display unit 117 is, for example, a liquid crystal display.

[0024] The communication interface 114 is configured to control communication between the control unit 11 and other devices.

[0025] Note that the configuration of the control unit 11 shown in Figure 2 is an example, and the configuration of the control unit 11 is not limited thereto. For example, the storage device 111 may be connected to the control unit 11 via a network. Also, at least one of the operation unit 116 and the display unit 117 may be implemented on an external input or output device connected to the control unit 11 via the input / output interface 113. Furthermore, the control unit 11 may not include the storage device 111 and the processor 112, and the drive circuit 115 may be configured to generate a predetermined drive signal in response to user input received via the input / output interface 113. Also, the drive circuit 115 may be configured to generate a drive signal based on instructions input from an external device via the communication interface 114.

[0026] (1-2) Configuration of the ultrasonic radiation unit The configuration of the ultrasonic radiation unit in this embodiment will be described. Figure 3 is a diagram illustrating the configuration of the ultrasonic radiation unit.

[0027] As shown in Figure 3, the ultrasonic radiation unit 15 includes a transducer disc 16 and a plurality of ultrasonic transducers 14. The plurality of ultrasonic transducers 14 are arranged along a horizontal plane that is aligned with the XY plane of the transducer disc 16, for example, in an array. The plurality of ultrasonic transducers 14 are configured to be driven according to a drive signal input from a drive circuit 115 and to emit ultrasonic waves.

[0028] The transducer disc 16 has a rectangular shape in the XY plane (i.e., a plan view from the Z direction (hereinafter simply referred to as "plan view")). The transducer disc 16 forms the radiating surface of the ultrasonic radiation unit 15. Multiple ultrasonic transducers 14 are arranged on the transducer disc 16 in a hexagonal shape in a plan view. Note that the shape of the transducer disc 16 and the arrangement of the ultrasonic transducers 14 are not limited to the example in Figure 3.

[0029] Figure 4 illustrates how ultrasonic waves emitted from the ultrasonic emission unit are focused. The control unit 11 drives each of the multiple ultrasonic transducers 14 at individual timings. The ultrasonic waves emitted from each ultrasonic transducer 14 have the same sound pressure. The ultrasonic waves emitted from the ultrasonic emission unit 15 have a phase difference corresponding to the time difference in the vibration of each ultrasonic transducer 14. As shown in Figure 4, the ultrasonic waves emitted from each of the multiple ultrasonic transducers 14 are focused at multiple focal points FP1 to FP3 located at a predetermined distance (hereinafter referred to as "focal distance") from the transducer disc 16. In other words, the ultrasonic emission unit 15 in this embodiment is configured to generate focused ultrasonic waves.

[0030] The control unit 11 can arbitrarily change the position of the focal point by controlling the timing of driving each ultrasonic transducer 14, as illustrated in Figure 4. Here, the focal length is expressed as the distance from the origin in a three-dimensional coordinate system where the reference point of the ultrasonic radiation unit 15 is the origin. For example, the focal length L1 of focal point FP1 is the distance between the origin (0,0,0) and FP1 (x1,y1,z1). The focal length L2 of focal point FP2 is the distance between the origin (0,0,0) and FP2 (x2,y2,z2). The focal length L3 of focal point FP3 is the distance between the origin (0,0,0) and FP3 (x3,y3,z3). In this way, the control unit 11 can three-dimensionally change the position of the focal point of the focused ultrasound emitted from the multiple ultrasonic transducers 14. Note that the position of the origin shown in Figure 4 can be arbitrarily changed.

[0031] Note that the configuration of the ultrasonic radiation unit 15 shown in Figures 3 and 4 is just one example, and the configuration of the ultrasonic radiation unit 15 is not limited thereto. For example, the transducer disc 16 may have a concave structure so that even if multiple ultrasonic transducers 14 emit ultrasound at the same phase, the ultrasound is focused at a specific focal point. Also, the focal point where the ultrasound emitted from the ultrasonic radiation unit 15 converges may be single or multiple. Furthermore, the focal point where the ultrasound emitted from the ultrasonic radiation unit 15 converges may be at a fixed position or a variable position relative to the transducer disc 16. In addition, the ultrasound emitted from the ultrasonic radiation unit 15 does not have to converge at a specific focal point; for example, the ultrasound emitted from the ultrasonic transducer 14 may spread radially or in a plane wave pattern. Furthermore, the ultrasonic transducer 14 provided in the ultrasonic radiation unit 15 may be single or multiple.

[0032] (2) Operation of the ultrasonic device The operation of the ultrasonic device 1 of this embodiment will be described.

[0033] As shown in Figure 1, the ultrasonic emission unit 15 of the ultrasonic device 1 irradiates the skin 10 at the vaccine injection site on the target with ultrasound based on a drive signal input from the control unit 11. Specifically, the drive circuit 115 generates a drive signal so that amplitude-modulated ultrasound at a predetermined frequency is emitted from the ultrasonic transducer 14. The multiple ultrasonic transducers 14 provided in the ultrasonic emission unit 15 are driven based on the drive signal and emit ultrasound. The ultrasound emitted by the multiple ultrasonic transducers 14 is focused at the location of the target skin 10, applying pressure (acoustic radiation pressure) to the skin 10 that varies according to the frequency described above.

[0034] When acoustic radiation pressure is applied to the target skin 10, cellular deformation occurs in the vicinity of the skin 10, and the expression of specific genes involved in antibody production due to vaccination increases. This increase in gene expression promotes antibody production when the target skin 10 is vaccinated, thereby improving the vaccine's effectiveness. Furthermore, since the stimulation from acoustic radiation pressure is not strong enough to damage the skin 10, it is possible to achieve both safety and vaccine effectiveness.

[0035] Thus, in this embodiment, the ultrasound device 1 irradiates the skin 10 at the vaccine injection site of the target with ultrasound based on a drive signal, thereby promoting antibody production by the vaccine in the target. Conventionally, adjuvants, which are pharmaceuticals, have been administered to enhance the effectiveness of vaccines, but such adjuvants carry the risk of side effects such as causing undesirable immune responses against autoantigens and damaging normal tissue. By using the ultrasound device 1 of this embodiment, the amount of conventional adjuvants administered with the vaccine can be reduced, or the administration of adjuvants can be eliminated, thereby reducing the risk of the aforementioned side effects. Furthermore, by using the ultrasound device 1 of this embodiment as a substitute for conventional adjuvants or in combination with conventional adjuvants, the effectiveness of the vaccine can be enhanced compared to conventional methods.

[0036] In this embodiment, the ultrasound device 1 controls the ultrasound waves emitted from multiple ultrasound transducers 14 to focus at a location on the target skin 10. This allows sufficient acoustic radiation pressure to be applied to the skin 10 even if the intensity of the ultrasound waves emitted from each ultrasound transducer 14 is low. However, if the intensity of the ultrasound waves emitted from each ultrasound transducer is sufficient, the ultrasound waves emitted from multiple ultrasound transducers 14 do not need to be focused, and the ultrasound device 1 may have only one ultrasound transducer 14. Furthermore, the ultrasound waves emitted from multiple ultrasound transducers 14 may be focused at multiple locations on the target skin 10. For example, the ultrasound device 1 may control the ultrasound waves emitted from the ultrasound transducers 14 to focus at multiple focal points, or it may be controlled so that the focal point where the ultrasound waves focus moves to multiple locations. This allows acoustic radiation pressure to be applied to a wider area on the target skin 10, thereby increasing gene expression in a wider range of cells and further enhancing the effectiveness of the vaccine.

[0037] In this embodiment, the ultrasonic device 1 is controlled so that amplitude-modulated ultrasound is emitted from the ultrasonic transducer 14 at a predetermined frequency. As a result, the acoustic radiation pressure from the ultrasound emitted from the ultrasonic transducer 14 provides the skin 10 with many pressure stimuli (vibrations) in a short period of time, thereby efficiently increasing gene expression in cells. Considering the response characteristics of the skin 10 to acoustic radiation pressure, it is desirable that the frequency used for amplitude modulation be approximately 10 Hz. However, the frequency used for amplitude modulation is not limited to this, and any frequency can be used. Alternatively, the ultrasonic device 1 may be controlled so that un-amplitude-modulated ultrasound is emitted from the ultrasonic transducer 14.

[0038] (3) Processing Flow of the Ultrasonic Device The processing flow of the ultrasonic device of this embodiment will be described. Figure 5 is a flowchart showing an example of the operation of the ultrasonic device. The processing flow in Figure 5 starts when the power of the ultrasonic device 1 is turned ON. However, the start timing of the processing flow in Figure 5 is not limited to this.

[0039] The control unit 11 performs input reception (S130). Specifically, the control unit 11 receives input from the user via the operation unit 116. User instructions include, for example, instructions relating to at least one of the following: - Start of ultrasonic emission - End of ultrasonic emission - Change of ultrasonic emission mode - Change of ultrasonic emission parameters User instructions may be given according to the type of vaccine to be administered to the target, and the control unit 11 may accept input according to the type of vaccine. If the ultrasonic device 1 is connected to an external device via the communication interface 114, the control unit 11 may also accept input from the external device.

[0040] The control unit 11 performs a determination (S131) ​​of whether or not to terminate the process. Specifically, if an instruction to terminate ultrasonic emission is input in S130, or if certain conditions are met, the control unit 11 determines to terminate the process and terminates the process shown in Figure 5. The specific conditions include, for example, that the ultrasonic emission time has reached a predetermined time, or that the skin 10 is no longer present in the direction of ultrasonic emission.

[0041] When the control unit 11 determines not to end the process in S131, it executes determination of control parameters (S132). Specifically, the control unit 11 determines control parameters according to the input received in S130. The control parameters include, for example, at least one of the following parameters regarding the ultrasonic waves emitted by the ultrasonic transducer 14: - Intensity - Phase - Carrier frequency - Modulation frequency - Modulation method - Radiation time - Radiation timing

[0042] The control unit 11 executes generation of a drive signal (S133). Specifically, the control unit 11 generates a drive signal for driving the ultrasonic transducer 14 based on the control parameters determined in S132. The generated drive signal is output to the ultrasonic radiation unit 15.

[0043] The ultrasonic radiation unit 15 executes irradiation of ultrasonic waves (S134). Specifically, the ultrasonic radiation unit 15 inputs the drive signal generated in S133 to the ultrasonic transducer 14, thereby irradiating the skin 10 at the vaccination position of the vaccine in the subject with ultrasonic waves based on the drive signal. The irradiated ultrasonic waves promote the production of antibodies by the vaccine in the subject and improve the effect of the vaccine.

[0044] After the end of S134, the ultrasonic device 1 returns to S130 to receive a new input.

[0045] (4) Example The example of this embodiment will be described. In this example, using the ultrasonic device 1 of this embodiment with mice as the experimental subjects, it was confirmed that the production of antibodies by the vaccine was promoted.

[0046] Four groups each containing seven 8-week-old normal mice (BALB / c) were prepared. The ultrasonic irradiation positions and vaccine inoculation positions in each group are as shown in Table 1 below.

[0047] For the ultrasonic waves to be irradiated, those obtained by amplitude-modulating 40 kHz ultrasonic waves at a frequency of 10 Hz were used. In the first group, ultrasonic waves focused at the position of the shaved back skin of the mice were irradiated for 20 minutes under intraperitoneal anesthesia. In the second group, ultrasonic waves focused at the position of the shaved thigh skin of the mice were irradiated for 20 minutes under intraperitoneal anesthesia. In the third and fourth groups, the mice were similarly anesthetized intraperitoneally, but ultrasonic wave irradiation was not performed.

[0048] Vaccination was carried out in two parts: the first vaccination and the second vaccination 14 days after the first one. For the first vaccination, an influenza vaccine (H1N1 hemagglutinin protein) mixed in equal amounts with complete Freund's adjuvant was used. For the second vaccination, an influenza vaccine (H1N1 hemagglutinin protein) mixed in equal amounts with incomplete Freund's adjuvant was used. In each of the first and second vaccinations, 100 μl of the vaccine was injected subcutaneously into the back of the mice in the first and third groups, and 50 μl of the vaccine was injected intramuscularly into the thigh of the mice in the second and fourth groups.

[0049] Figure 6 is a diagram explaining the implementation timing of vaccination, ultrasonic wave irradiation, and serum collection in this example. As shown in Figure 6, the above-mentioned intraperitoneal anesthesia and ultrasonic wave irradiation were each performed once a day for a total of 5 days, including the day of vaccination and the two days before and after for each of the two vaccinations.

[0050] Fourteen days after the second vaccination, serum was collected from the mice in each group, and influenza antibodies (anti-HA-IgG) were quantified by the ELISA method. The ultrasonic wave irradiation groups (the first and second groups) and the non-irradiation groups (the third and fourth groups) were compared. For statistical analysis, GraphPad Prism, version 10 (GraphPad Software, La Jolla, CA, USA) was used. In the comparison between the irradiation group and the non-irradiation group, analysis was performed using the Mann-Whitney U test, and the significance level was set at P < 0.05.

[0051] Figure 7 shows the analysis results in this example. Figure 7(a) shows the analysis results comparing Group 1 (non-irradiated group) and Group 3 (irradiated group), both of whom received the vaccine subcutaneously on their backs. The vertical axis of the graph represents absorbance, which indicates the amount of antibodies contained in the serum. In the comparison between Group 1 and Group 3, P = 0.0728, and no statistically significant difference was obtained. However, a trend of increased antibody levels was observed in Group 1, which received ultrasound irradiation, compared to Group 3, which did not receive ultrasound irradiation.

[0052] Figure 7(b) shows the analysis results comparing Group 2 (non-irradiated group) and Group 4 (irradiated group), both of which received the vaccine intramuscularly in the thigh. In the comparison between Group 2 and Group 4, P = 0.0041, indicating a significantly higher antibody level in Group 2, which received ultrasound irradiation, compared to Group 4, which did not receive ultrasound irradiation.

[0053] The results above demonstrate that the irradiation of the target skin with ultrasound by the ultrasound device 1 in this embodiment promotes the production of antibodies induced by the vaccine in the target, thereby enhancing the effectiveness of the vaccine.

[0054] (5) Summary As described above, the ultrasonic device 1 of this embodiment generates a drive signal to drive the ultrasonic transducer 14 that emits ultrasonic waves. The ultrasonic device 1 then irradiates the skin 10 at the vaccine injection site on the subject with ultrasonic waves based on the drive signal, thereby promoting antibody production by the vaccine on the subject. This makes it possible to enhance the effect of the vaccine using ultrasound.

[0055] The ultrasonic device 1 may receive input according to the type of vaccine and generate a drive signal based on parameters determined according to that input. This allows an appropriate acoustic radiation pressure to be applied to the target skin 10 according to the type of vaccine. As a result, antibody production by the vaccine can be effectively promoted, and the effectiveness of the vaccine can be further enhanced.

[0056] (6) Explain the modified examples.

[0057] (6-1) Modification 1 Modification 1 will now be explained. In Modification 1, the ultrasonic device determines the control parameters used to generate the drive signal based on various information acquired by the control unit 11. Figure 8 is a flowchart showing an example of the operation of the ultrasonic device. The processing flow in Figure 8 starts at the same timing as the processing flow in Figure 5. The same reference numerals are used for the same processes as those explained using Figure 5, and the following explanation will focus on the differences from the processes in Figure 5.

[0058] After receiving input in S130, the control unit 11 performs information acquisition (S150). Specifically, the control unit 11 acquires information via the input / output interface 113 or the communication interface 114. The information to be acquired includes at least one of the following: - Information indicating the type of vaccine to be administered to the subject - Attribute information of the subject (e.g., species, age, or sex) - Physical information of the subject (e.g., height or weight) - Disease information of the subject (e.g., medical history or presence of allergies) - Biological information of the subject (e.g., body temperature, blood pressure, or heart rate) - Diagnostic information of the subject (e.g., test data or results of a doctor's examination)

[0059] In S132, the control unit 11 performs the determination of control parameters. Specifically, the control unit 11 determines the control parameters based on the information acquired in S150. The control parameters include, for example, at least one of the following parameters relating to the ultrasound emitted by the ultrasonic transducer 14: intensity, phase, carrier frequency, modulation frequency, modulation method, radiation time, and radiation timing.

[0060] In S133, the control unit 11 generates a drive signal to drive the ultrasonic transducer 14 based on the control parameters determined in S132. The generated drive signal is output to the ultrasonic radiation unit 15.

[0061] According to Modification 1, the ultrasound device 1 acquires at least one of the following information: attribute information, physical information, disease information, biological information, and diagnostic information of the target, and generates a drive signal based on parameters determined according to that information. This makes it possible to apply an appropriate acoustic radiation pressure to the target's skin 10 for the target receiving the vaccine, thereby enhancing the effectiveness of the vaccine.

[0062] (6-2) Modification 2 Modification 2 will now be explained. The ultrasonic device of Modification 2 detects the vaccine injection site and controls the direction of ultrasound emission based on the detection result. Figure 9 is a schematic diagram showing the configuration of the ultrasonic device. Components similar to those described using Figure 1 are given the same reference numerals, and the following explanation will focus on the differences from the configuration of Figure 1.

[0063] As shown in Figure 9, the ultrasonic device 2 includes a control unit 11, an ultrasonic radiation unit 15, and a sensor 20. The control unit 11 and the sensor 20 are connected by wire or wireless.

[0064] The control unit 11 controls the ultrasonic emission unit 15 and the sensor 20. Specifically, the control unit 11 controls the sensor 20 and, based on the information acquired, generates a drive signal to drive the ultrasonic transducer 14 of the ultrasonic emission unit 15, and outputs the drive signal to the ultrasonic emission unit 15.

[0065] The sensor 20 detects the vaccine injection site on the target based on control by the control unit 11 and outputs information indicating the detection result to the control unit 11. The sensor 20 is, for example, an imaging sensor (camera) that captures images, a distance sensor that measures distance, or a position sensor that detects the position of a wireless tag. The following explanation will mainly focus on the case where the sensor 20 is a camera, but the type of sensor is not limited to this.

[0066] Figure 10 is a block diagram showing the functional configuration of the control unit. Components similar to those described using Figure 2 are denoted by the same reference numerals, and the following explanation will focus on the differences from the configuration in Figure 2.

[0067] As shown in Figure 10, the communication interface 114 is configured to control communication between the control unit 11 and the sensor 20. Specifically, it sends instructions to the sensor 20 to control it and receives information from the sensor 20 indicating the vaccine administration location detected by the sensor 20.

[0068] Figure 11 is a flowchart showing an example of the operation of an ultrasonic device. The processing flow in Figure 11 starts at the same timing as the processing flow in Figure 5. Processes similar to those explained using Figure 5 are denoted by the same reference numerals, and the following explanation will focus on the differences from the processing in Figure 5.

[0069] After receiving the input in S130, the control unit 11 performs the acquisition of the detection result (S170). Specifically, the control unit 11 controls the sensor 20. The sensor 20 captures an image of the vicinity of the target skin 10 to generate image data and performs image analysis (e.g., feature analysis) to detect the vaccine injection site on the target.

[0070] As an example of the detection method, a physician or the subject themselves attaches a marker to the skin 10 at the site where the vaccine has been administered or is scheduled to be administered to the subject. The sensor 20 detects the marker from the captured image and identifies the position of the marker based on the position and orientation of the sensor 20 and the coordinates of the marker in the captured image. The sensor 20 then transmits the identified marker position to the control unit 11 as the detection result of the vaccine administration site on the subject.

[0071] As another example of the detection method, the sensor 20 images the vicinity of the target's skin 10 after the target has been vaccinated. The sensor 20 detects the vaccination site from the captured image and identifies the location of the vaccination site based on the position and orientation of the sensor 20 and the coordinates of the vaccination site in the captured image. The sensor 20 then transmits the identified location of the vaccination site to the control unit 11 as the detection result of the vaccination site on the target.

[0072] After it is determined in S131 to continue processing, the control unit 11 performs radiation direction control (S171). Specifically, the control unit 11 controls the direction of the ultrasound emitted from the ultrasound transducer 14 so that ultrasound is irradiated onto the skin 10 at the injection site detected in S170.

[0073] As an example of controlling the direction of emission, the ultrasonic emission unit 15 has a drive mechanism (e.g., an actuator) for changing the orientation of the ultrasonic transducer 14. The control unit 11 controls the direction of ultrasonic emission by outputting a signal to the ultrasonic emission unit 15 to control the drive mechanism of the ultrasonic emission unit 15 based on the information indicating the detection result of the inoculation position acquired in S170.

[0074] As another example of controlling the direction of emission, the control unit 11 controls the phase of the ultrasound emitted from the multiple ultrasonic transducers 14 by adjusting the drive signal output from the drive circuit 115 to the ultrasonic emission unit 15 based on the information indicating the detection result of the inoculation position acquired in S170. As explained with reference to Figure 4, the position where the ultrasound is focused can be changed by controlling the phase of the ultrasound emitted from the ultrasonic transducers 14. Furthermore, if the ultrasound emitted from the multiple ultrasonic transducers 14 spreads out in a plane wave shape, the direction of propagation of the emitted ultrasound can be changed by controlling the phase of the ultrasound emitted from the ultrasonic transducers 14. In this way, the control unit 11 controls the direction of ultrasound emission by controlling the phase of the ultrasound emitted from the ultrasonic transducers 14.

[0075] In S132, the control unit 11 performs the determination of control parameters. Specifically, the control unit 11 determines the control parameters according to at least one of the input received in S130 and the detection result obtained in S170. The control parameters include, for example, at least one of the following parameters relating to the ultrasound emitted by the ultrasound transducer 14: intensity, phase, carrier frequency, modulation frequency, modulation method, radiation time, and radiation timing. For example, the control unit 11 may determine the parameters relating to the intensity of the ultrasound emitted by the ultrasound transducer 14 based on the distance between the vaccine injection site indicated by the detection result and the position of the ultrasound transducer 14, so that ultrasound of appropriate intensity is irradiated onto the skin 10. The control unit 11 may also determine the parameters relating to the phase of the ultrasound emitted by the ultrasound transducer 14 based on the relative position between the vaccine injection site indicated by the detection result and the position of the ultrasound transducer 14, so that the ultrasound is focused at the location of the skin 10.

[0076] In S133, the control unit 11 generates a drive signal to drive the ultrasonic transducer 14 based on the control parameters determined in S132. The generated drive signal is output to the ultrasonic radiation unit 15.

[0077] In S134, the ultrasonic radiation unit 15 inputs the drive signal generated in S133 to the ultrasonic transducer 14, thereby irradiating the skin 10 at the vaccine injection site on the target with ultrasound based on the drive signal.

[0078] According to Modification 2, the ultrasound device 2 detects the vaccine injection site on the subject. The ultrasound device 2 then controls the direction of the ultrasound emitted from the ultrasound transducer 14 so that ultrasound based on the drive signal is irradiated onto the skin 10 at the detected injection site on the subject. This allows for more accurate irradiation of the skin 10 at the injection site with ultrasound, thereby enhancing the effectiveness of the vaccine.

[0079] (6-3) Modification 3 Modification 3 will now be explained. In Modification 3, the system consists of an ultrasound device that irradiates the target with ultrasound and an inoculation device that administers the vaccine to the target. Figure 12 is a schematic diagram showing the system configuration. Components similar to those described using Figure 1 are denoted by the same reference numerals, and the following explanation will focus on the differences from the configuration in Figure 1.

[0080] As shown in Figure 12, the system 300 comprises an ultrasonic device 1 and an inoculation device 30. The inoculation device 30 and the control unit 11 of the ultrasonic device 1 are connected by wire or wireless.

[0081] The vaccination device 30 administers the vaccine to the target based on the control of the control unit 11.

[0082] The ultrasonic device 1 comprises a control unit 11 and an ultrasonic emission unit 15. The control unit 11 and the ultrasonic emission unit 15 are connected by wire or wireless.

[0083] The ultrasonic emission unit 15 has an ultrasonic transducer 14 that emits ultrasonic waves, and irradiates the skin 10 at the vaccine injection site on the subject with ultrasonic waves based on a drive signal input from the control unit 11, thereby promoting antibody production by the vaccine on the subject.

[0084] The control unit 11 controls the ultrasonic emission unit 15 and the vaccination device 30. Specifically, the control unit 11 generates a drive signal to drive the ultrasonic transducer 14 of the ultrasonic emission unit 15 and outputs it to the ultrasonic emission unit 15. The control unit 11 also outputs an instruction to the vaccination device 30 to administer the vaccine and obtains the result of the vaccine administration from the vaccination device 30.

[0085] The control unit 11 may irradiate the target's skin with ultrasound based on a drive signal after the target has been vaccinated with the vaccine by the vaccination device 30. In this case, the irradiation of ultrasound increases the expression of specific genes in cells that are producing antibodies in response to the vaccine, thereby promoting antibody production. As a result, the effectiveness of vaccination can be improved.

[0086] The control unit 11 may irradiate the target's skin with ultrasound based on a drive signal before the vaccine is administered to the target by the vaccination device 30. In this case, cells with increased expression of specific genes due to ultrasound irradiation will react to the vaccine and produce antibodies, thereby promoting antibody production more than when ultrasound irradiation is not performed. As a result, the effectiveness of vaccination can be improved.

[0087] The control unit 11 may, at the same time that the vaccine is administered to the target by the inoculation device 30, irradiate the target's skin with ultrasound based on a drive signal.

[0088] Furthermore, the inoculation device 30 may administer an adjuvant to the target along with the vaccine. The type of adjuvant is not limited, but may include at least one of the following: metal salts, low molecular weight compounds, polypeptides, nucleic acids, and proteins (such as cytokines). In this case, the antibody production-promoting effect of the administered adjuvant and the antibody production-promoting effect of the ultrasound irradiation from the ultrasound device 1 can be combined to further improve the effectiveness of the vaccine.

[0089] (6-4) Other Modifications The above-described embodiments demonstrated that irradiating the target skin with ultrasound using the ultrasound device of this embodiment enhances the effectiveness of the influenza vaccine. However, the target diseases of vaccines to which the ultrasound device can be applied are not limited to influenza vaccines. The effectiveness of vaccines can also be improved by irradiating the skin of a person receiving a vaccine for a different target disease (for example, a vaccine for herpes zoster, COVID-19, or herpes simplex) with ultrasound using the ultrasound device 1. Furthermore, the vaccine to which the ultrasound device 1 can be applied is not limited to antiviral vaccines, but may also be so-called immunotherapy vaccines (for example, cancer vaccines or dermatofibrosis vaccines). Also, the type of vaccine to which the ultrasound device 1 can be applied is not limited, and may include, for example, inactivated vaccines, live vaccines, toxoids, recombinant protein vaccines, or mRNA vaccines.

[0090] In the above embodiment, the ultrasound emitted from the ultrasound device has a frequency of 40 kHz. However, the frequency of the ultrasound emitted from the ultrasound device is not limited to this; any frequency that can apply acoustic radiation pressure to the target skin is acceptable.

[0091] In the above-described embodiment, ultrasound irradiation was performed over a total of five days, including the day of vaccination and the two days before and after. However, the timing and number of ultrasound irradiations by the ultrasound device are not limited to this. It is sufficient for ultrasound irradiation to be performed at least once, either before or after vaccination.

[0092] In the above-described modification 2, the case in which the direction of ultrasound emitted from the ultrasonic transducer is controlled based on the detection result of the vaccine injection site was explained. However, the method of controlling the direction of emitted ultrasound is not limited to this. For example, the control unit of the ultrasonic device may receive input in response to user operation to specify the direction of ultrasound emitted from the ultrasonic transducer and control the direction of ultrasound emission in response to said input. Specifically, the control unit may control the drive mechanism of the ultrasonic emission unit 15 based on input in response to user operation, or it may control the phase of ultrasound emitted from a plurality of ultrasonic transducers 14. In addition, the control unit of the ultrasonic device may receive instructions from an external device to specify the direction of ultrasound emitted from the ultrasonic transducer and control the direction of ultrasound emission in response to said instructions.

[0093] Although embodiments of the present invention have been described in detail above, the scope of the present invention is not limited to the embodiments described above. Furthermore, the embodiments described above can be improved or modified in various ways without departing from the spirit of the present invention. In addition, the embodiments and modifications described above can be combined.

[0094] 1 Ultrasound device 10 Skin 11 Control unit 14 Ultrasound transducer 15 Ultrasound radiation unit

Claims

1. An ultrasonic device comprising: means for generating a drive signal for driving an ultrasonic transducer that emits ultrasonic waves; and means for irradiating the skin at the vaccine injection site on a target with ultrasonic waves based on the drive signal to promote antibody production by the vaccine on the target.

2. The ultrasonic apparatus according to claim 1, wherein the means for generating the drive signal generates the drive signal such that ultrasonic waves amplitude-modulated at a predetermined frequency are emitted from the ultrasonic transducer, and the ultrasonic waves based on the drive signal apply pressure to the target skin that varies according to the predetermined frequency.

3. The ultrasonic device according to claim 2, wherein the predetermined frequency is approximately 10 Hz.

4. An ultrasonic device according to any one of claims 1 to 3, comprising a plurality of ultrasonic transducers driven based on the drive signal, wherein the ultrasonic waves emitted by the plurality of ultrasonic transducers are focused at the location of the target skin.

5. The ultrasonic device according to claim 4, wherein the ultrasonic waves emitted by the plurality of ultrasonic transducers are focused at a plurality of locations on the skin of the target.

6. The ultrasonic device according to any one of claims 1 to 5, comprising means for receiving input according to the type of vaccine, wherein means for generating a drive signal generates the drive signal based on parameters determined according to the input.

7. An ultrasonic apparatus according to any one of claims 1 to 6, comprising means for acquiring at least one of the attribute information, physical information, disease information, biological information and diagnostic information of the subject, wherein the means for generating the drive signal generates the drive signal based on parameters determined according to the acquired information.

8. The ultrasonic apparatus according to claim 6 or 7, wherein the parameters include parameters relating to at least one of the intensity, phase, carrier frequency, modulation frequency, modulation scheme, radiation time, and radiation timing of the ultrasonic waves emitted by the ultrasonic transducer.

9. An ultrasonic device according to any one of claims 1 to 8, comprising: means for detecting the injection site of the vaccine in a target; and means for controlling the direction of ultrasonic waves emitted from the ultrasonic transducer so that ultrasonic waves based on the drive signal are irradiated onto the skin at the detected injection site in the target.

10. The ultrasonic device according to any one of claims 1 to 9, wherein the vaccine is an influenza vaccine.

11. A system comprising an ultrasonic device having an ultrasonic transducer that emits ultrasonic waves, and an inoculation device for inoculating a target with a vaccine, wherein the ultrasonic device comprises means for generating a drive signal for driving the ultrasonic transducer, and means for irradiating the skin at the vaccine inoculation site on the target with ultrasonic waves based on the drive signal to promote antibody production by the vaccine in the target.

12. The system according to claim 11, wherein the ultrasonic device irradiates the skin of the target with ultrasonic waves based on the drive signal before the target is inoculated with the vaccine by the inoculation device.

13. The system according to claim 11, wherein the ultrasonic device irradiates the skin of the target with ultrasound based on the drive signal after the target has been inoculated with the vaccine by the inoculation device.

14. The system according to any one of claims 11 to 13, wherein the inoculation device administers an adjuvant together with the vaccine to the subject.

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