A multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system

Abstract

The present invention discloses a multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system, including: an ultrasonic transdermal drug delivery system and an ultrasonic visualization monitoring system, an ultrasonic electronic control system, the ultrasonic transdermal drug delivery system includes: a signal generator, an ultrasonic transducer, an ultrasonic microbubble transdermal drug delivery device; the ultrasonic visualization monitoring system includes: a time gain compensation circuit, a filter sequence and a power amplifier array, a high-efficiency noise amplifier and an ultrasonic imaging monitoring probe. The present invention overcomes the single frequency through the dual-frequency design of the ultrasonic transducer; the ultrasonic electronic control system accurately drives the transducer to achieve dual-frequency ultrasonic output, and through the ultrasonic visualization monitoring system and the ultrasonic microbubble transdermal drug delivery device, ultrasonic treatment and transdermal drug delivery under real-time navigation and monitoring are realized, thereby improving the efficiency and accuracy of drug delivery.

Description

Technical Field

[0001] The invention relates to the field of ultrasonic therapy, and more specifically to a multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery therapy and real-time ultrasonic visualization monitoring system. Background Art

[0002] Ultrasound, as a mechanical wave, has been used in rehabilitation medicine for decades and is still playing an important role in treating soft tissue injuries, promoting nerve regeneration, loosening scars, etc. Ultrasonic radiation does not destroy the activity of drugs, and has a significant penetration-enhancing effect on fat-soluble and water-soluble drugs including biomacromolecules, and can reach the deep tissues of the skin. Therefore, the research on establishing a transdermal drug delivery system using ultrasound to enhance percutaneous penetration is in full swing.

[0003] In the past few decades, ultrasound therapy has mostly used 800kHz continuous waves. In recent years, the application of 1-3MHz high-frequency ultrasound and 20-50kHz low-frequency ultrasound or pulsed ultrasound has also been developed. However, because the intensity of ultrasound decreases sharply with the propagation distance during the propagation of the medium, and the higher the ultrasound frequency, the more ultrasound attenuation and the smaller the penetration ability when propagating in biological tissues, and vice versa, which means that the use of a single frequency ultrasound to treat lesions of different depths is blind. Moreover, in the process of clinical treatment of diseases, the selection of ultrasound treatment sites is mostly based on clinical experience, and the accurate location of the treatment site lacks the necessary objective basis. The currently used ultrasound therapeutic device is far from achieving the purpose of precise treatment. In addition, in clinical practice, the effect of simple ultrasound treatment is limited, and the effect of combined drug treatment is more obvious. At present, ultrasound-enhanced transdermal drug delivery has been used clinically, but the efficiency of ultrasound drug delivery still has a lot of room for improvement, especially when combined with other permeation-enhancing transdermal drug delivery methods, the impact of other permeation-enhancing drug delivery methods on the efficiency of ultrasound transdermal drug delivery needs to be considered.

[0004] Currently, the frequency of ultrasonic treatment is single, the treatment effect is blind, and the efficiency of ultrasonic drug delivery is low, which needs to be solved urgently. Summary of the invention

[0005] In order to overcome the defects of the prior art in that the ultrasonic treatment frequency is single, the treatment effect is blind, and the ultrasonic drug delivery efficiency is low, the present invention provides a multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system.

[0006] The primary purpose of the present invention is to solve the above technical problems. The technical solution of the present invention is as follows:

[0007] A multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system comprises: an ultrasonic transdermal drug delivery system, an ultrasonic visualization monitoring system, and an ultrasonic electronic control system.

[0008] The ultrasonic transdermal drug delivery system comprises: a signal generator, an ultrasonic transducer, and an ultrasonic microbubble transdermal drug delivery device;

[0009] The ultrasonic visualization monitoring system comprises: a time gain compensation circuit, a filter sequence and a power amplifier array, a high-efficiency noise amplifier and an ultrasonic imaging monitoring probe;

[0010] The output end of the ultrasonic imaging monitoring probe is connected to the input end of the high-efficiency noise amplifier, the output end of the high-efficiency noise amplifier is connected to the time gain compensation circuit through the power amplifier array and the filter sequence in sequence, and the output end of the time gain compensation circuit is connected to the input end of the ultrasonic electronic control system through the AD converter;

[0011] The output end of the ultrasonic electronic control system is connected to the input end of the signal generator through the main clock and the delay device in sequence, and the output end of the signal generator is connected to the ultrasonic transducer;

[0012] The ultrasonic electronic control system is used to generate control electrical signals, control the acoustic radiation force pulse sequence and the sharp imaging pulse sequence generated by the ultrasonic transducer, and realize the precise driving of the low-frequency peripheral annular array element array and the high-frequency central array element;

[0013] The ultrasonic transducer is used to generate low-frequency peripheral annular array element array and high-frequency central array element ultrasonic waves;

[0014] The ultrasonic microbubble transdermal drug delivery device is used to immerse the ultrasonic transducer in a liquid filled with drug-loaded ultrasonic microbubbles and directly contact and fix it on the skin to achieve transdermal drug delivery;

[0015] The ultrasonic visualization monitoring system locates the treatment site, drug administration site and depth, and adjusts the ultrasonic output mode, frequency and intensity, the penetration direction, depth, penetration amount and microbubble breaking timing of the drug-loaded ultrasonic microbubble transdermal drug delivery device to achieve accurate and efficient drug administration.

[0016] The present invention controls the high-power acoustic radiation force pulse sequence and sharp imaging pulse sequence generated by the transducer through an ultrasonic electronic control system, thereby realizing precise driving of the low-frequency ring array and high-frequency array element of the ultrasonic transducer, and realizing the dynamic output of the lesion area of ​​interest simultaneously or alternately in real time by dual-frequency ultrasound; through the ultrasonic microbubble effect of the ultrasonic microbubble transdermal drug delivery device, ultrasonic treatment and transdermal drug delivery under real-time navigation and monitoring are realized. The ultrasonic visualization monitoring system locates the treatment site and the drug delivery site, and visualizes the environment of the treatment site and the drug delivery site on the system, which plays the role of monitoring and adjusting the treatment plan. The ultrasonic visualization monitoring system is combined with the ultrasonic microbubble transdermal device to achieve precise treatment and ultrasonic permeation directional drug delivery.

[0017] Furthermore, the ultrasonic transducer is a dual-frequency multi-element 2-ring array ultrasonic transducer, the central operating frequency of the middle element of the dual-frequency element 2-ring array ultrasonic transducer is 1-3MHz, the operating frequency of the peripheral ring array elements is set to be greater than 20KHz, and the middle element and the peripheral ring array elements can be synchronized or alternated. The present invention realizes a dual-frequency mode of high frequency of the central element and low frequency of the ring array elements.

[0018] Furthermore, the peripheral ring array elements of the dual-frequency multi-element 2-ring array ultrasonic transducer work simultaneously and emit ultrasonic waves a and b at the same position, wherein the frequency of ultrasonic wave a is >20KHz, and the frequency of ultrasonic wave b is 1-3MHz.

[0019] Furthermore, the power of the ultrasound waves between the different array elements is adjustable within a certain range, and pulse or continuous ultrasound waves can be set.

[0020] Furthermore, the transmitting circuit of the ultrasonic electronic control system can control the gating or closing of each transmitting channel, and can configure control parameters, the parameters include: configuring the transmitting pulse frequency, transmitting pulse amplitude, and transmitting mode, and the transmitting mode includes: pulse transmission or continuous transmission. The control parameters are configured to achieve an optimized transdermal drug delivery effect. In the present invention, the ultrasonic electronic control system circuit adopts an integrated chip design method, which reduces the interference caused by separate components and improves the sensitivity and accuracy of control. In the ultrasonic electronic control system of the present invention, the circuit board design is wired according to the design specifications of the high-frequency circuit, which further reduces the interference of the analog circuit part and the digital circuit part.

[0021] Furthermore, the ultrasonic microbubble transdermal drug delivery device is used for transdermal drug delivery in cooperation with the probe of the ultrasonic transducer; the ultrasonic microbubble transdermal drug delivery device comprises: a circular plastic shell, the interior of the circular plastic shell is a drug-carrying cavity; a first circular hole and a second circular hole are provided at the upper part of the drug-carrying cavity, the diameter of the first circular hole is larger than the diameter of the second circular hole, the first circular hole is connected to the ultrasonic transducer, and the second circular hole is used for injecting drug liquid; the ultrasonic microbubbles of the ultrasonic microbubble transdermal drug delivery device are placed in the drug-carrying cavity; the circular opening below the drug-carrying cavity is directly adhered to the skin, and a waterproof skin patch is surrounded at the bottom of the shell for sticking the ultrasonic microbubble transdermal drug delivery device on the skin; water or drug solution is injected into the drug-carrying cavity through the second circular hole of the drug-carrying cavity, the water or drug solution is fully mixed with the ultrasonic microbubbles, and can be used as a coupling agent between the ultrasonic transducer probe and the skin, and at the same time as a carrier for the drug to be introduced. In the present invention, when the drug-carrying cavity is connected and fitted with the ultrasonic probe of the transducer, water or drug solution needs to cover the ultrasonic probe to a certain depth to ensure that no air gap appears between the probe and the drug-carrying liquid, reduce ultrasonic reflection and scattering, and prevent attenuation of ultrasonic action intensity. Immersion coupling is the preferred coupling method.

[0022] Furthermore, the ultrasonic microbubble transdermal drug delivery device comprises ultrasonic microbubbles, and the shell of the ultrasonic microbubbles comprises one or more of proteins, lipids, sugars or polymer compounds.

[0023] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0024] The present invention overcomes the defect of blindness in single-frequency treatment by designing an ultrasonic transducer with a low-frequency ring array and a high-frequency central array element; the ultrasonic electronic control system accurately drives the low-frequency ring array and the high-frequency array element of the ultrasonic transducer to realize dynamic emission at different depths of the lesion area; through the microbubble effect of ultrasound and ultrasonic microbubble transdermal drug delivery device, ultrasonic treatment and transdermal drug delivery under real-time navigation and monitoring are realized, thereby improving the efficiency and accuracy of ultrasonic drug delivery. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Schematic diagram of the system of the present invention.

[0026] Figure 2 This is a schematic diagram of the structure of the ultrasonic microbubble transdermal drug delivery device.

[0027] Figure 3 A schematic diagram of an ultrasonic microbubble transdermal drug delivery device for cooperating with an ultrasonic transducer probe. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described below in conjunction with the accompanying drawings and embodiments.

[0029] Example 1

[0030] like Figure 1 As shown, a multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system includes: an ultrasonic transdermal drug delivery system and an ultrasonic visualization monitoring system, and an ultrasonic electronic control system. The ultrasonic transdermal drug delivery system includes: a signal generator, an ultrasonic transducer, and an ultrasonic microbubble transdermal drug delivery device; the ultrasonic visualization monitoring system includes: a time gain compensation circuit, a filter sequence and a power amplifier array, a high-efficiency noise amplifier (i.e., a high-efficiency LNA), and an ultrasonic imaging monitoring probe;

[0031] The output end of the ultrasonic imaging monitoring probe is connected to the input end of the high-efficiency noise amplifier, the output end of the high-efficiency noise amplifier is connected to the time gain compensation circuit through the power amplifier array and the filter sequence in sequence, and the output end of the time gain compensation circuit is connected to the input end of the ultrasonic electronic control system through the AD converter;

[0032] The output end of the ultrasonic electronic control system is connected to the input end of the signal generator through the main clock and the delay device in sequence, and the output end of the signal generator is connected to the ultrasonic transducer;

[0033] The ultrasonic transducer is a dual-frequency multi-element 2-ring array ultrasonic transducer, the central operating frequency of the middle element of the dual-frequency multi-element 2-ring array ultrasonic transducer is 1-3MHz, the operating frequency of the peripheral ring array elements is set to be greater than 20KHz, and the middle element and the peripheral ring array elements can output synchronously or alternately. The present invention realizes a dual-frequency mode of high frequency of the central element and low frequency of the ring array elements. The peripheral ring array elements of the dual-frequency multi-element 2-ring array ultrasonic transducer work simultaneously and emit ultrasonic waves a and b focused on the same position, wherein the frequency of ultrasonic wave a is>20KHz, and the frequency of ultrasonic wave b is 1-3MHz.

[0034] The ultrasonic output mode and intensity can be adjusted between different elements of the peripheral ring array. This ensures that the power of the ultrasonic wave is within a certain range (0.5W / cm 2 -3W / cm 2 ) and can be set to pulse or continuous ultrasound.

[0035] The ultrasonic electronic control system is used to generate control electrical signals to control the high-power acoustic radiation force pulse sequence and sharp imaging pulse sequence generated by the ultrasonic transducer and to achieve precise driving of the low-frequency ring array and the high-frequency center array element;

[0036] The ultrasonic transducer is used to generate low-frequency peripheral annular array element array and high-frequency central array element ultrasonic waves;

[0037] The radio frequency transmitting circuit of the ultrasonic electronic control system uses the HV732 chip to directly output high-voltage signals; the ultrasonic signal pre-amplification circuit, bandpass circuit, and data acquisition circuit of the ultrasonic electronic control system are implemented using the integrated chip AD9272. The transmitting circuit of the ultrasonic electronic control system can control the gating or closing of each transmitting channel, and can also configure control parameters, including: configuring the transmitting pulse frequency, transmitting pulse amplitude, and transmitting mode, and the transmitting mode includes: pulse transmission or continuous transmission, etc.

[0038] In the present invention, the circuit of the ultrasonic electronic control system adopts the design mode of integrated chip, which reduces the interference caused by separate components and improves the sensitivity and accuracy of control. In the ultrasonic electronic control system of the present invention, the control circuit board design is wired according to the design specification of high-frequency circuit, which further reduces the interference of analog circuit part and digital circuit part. The power supply of the ultrasonic electronic control system is a power supply with the function of reducing ripple interference.

[0039] The ultrasonic microbubble transdermal drug delivery device is used for immersing the ultrasonic transducer into the liquid full of drug-loaded ultrasonic microbubbles and directly contacting and being fixed on the skin to realize transdermal drug delivery, by coupling the ultrasonic microbubble transdermal drug delivery device with the device of ultrasonic transducer, reduce ultrasonic energy attenuation, make the sound field fully drive the drug-loaded ultrasonic microbubbles to enter the human body, improve transdermal drug delivery efficiency. The ultrasonic wave that ultrasonic transducer produces different frequencies can be used to adjust the penetration of medicine different depths, as only skin surface medicine is penetrated, high frequency (1-3MHz) can be selected, as deep penetration is needed, available low frequency (20KHz), or high and low frequency are synchronously and alternately penetrated. And in different stages of drug penetration, different intensities of ultrasonic wave can be selected, first low-intensity ultrasound (for example <1W / cm2) is selected for driving microbubbles to penetrate the human body, when the visual display system prompts that the microbubble majority has reached the treatment site, high-intensity ultrasound (>1W / cm2) can be selected to break microbubbles and promote drug absorption.

[0040] The ultrasonic visualization monitoring system locates the treatment site, drug administration site and depth, and adjusts the ultrasonic output mode, frequency and intensity, the penetration direction, depth, penetration amount and microbubble breaking timing of the drug-loaded ultrasonic microbubble transdermal drug delivery device to achieve accurate and efficient drug administration.

[0041] Figure 2 A schematic structural diagram of an ultrasonic microbubble transdermal drug delivery device is shown.

[0042] Figure 3 A schematic diagram showing an ultrasonic microbubble transdermal drug delivery device for cooperating with a probe of an ultrasonic transducer is shown. Figure 3 In the figure, 6 represents an ultrasonic transducer, 601 represents an ultrasonic transducer handle, and 602 represents an ultrasonic transducer probe.

[0043] In the present invention, the ultrasonic microbubble transdermal drug delivery device is used for transdermal drug delivery in cooperation with the probe of the ultrasonic transducer; the ultrasonic microbubble transdermal drug delivery device comprises: a circular plastic shell 1, the interior of the circular plastic shell 1 is a drug-carrying cavity 2; a first circular hole 3 and a second circular hole 4 are provided on the upper part of the drug-carrying cavity 2, the diameter of the first circular hole 3 is larger than the diameter of the second circular hole 4, the first circular hole 3 is connected to the ultrasonic transducer, and the second circular hole 4 is used for injecting drug solution; ultrasonic microbubbles of the ultrasonic microbubble transdermal drug delivery device are placed in the drug-carrying cavity 2; the circular opening below the drug-carrying cavity 2 is directly adhered to the skin, and a waterproof skin patch 5 is surrounded below the shell for sticking the ultrasonic microbubble transdermal drug delivery device on the skin; water or drug solution is injected into the drug-carrying cavity 2 through the second circular hole 4 of the drug-carrying cavity 2, the water or drug solution is fully mixed with the ultrasonic microbubbles, and can be used as a coupling agent between the ultrasonic transducer probe and the skin, and at the same time as a carrier of the drug to be introduced. In the present invention, when the drug-carrying cavity is connected and matched with the ultrasonic probe of the circulator, water or drug solution needs to cover the ultrasonic probe to a certain depth to ensure that there is no air gap between the probe and the drug-carrying liquid, reduce ultrasonic reflection and scattering, and prevent attenuation of ultrasonic action intensity. Immersion coupling is the preferred coupling method.

[0044] In the present invention, the ultrasonic microbubble transdermal drug delivery device comprises ultrasonic microbubbles, and the shell of the ultrasonic microbubbles comprises one or more of proteins, lipids, sugars or polymer compounds.

[0045] The selection and application of the ultrasonic microbubbles are:

[0046] The ultrasonic microbubbles can be purchased or prepared according to clinical application requirements. Commonly used microbubble shells are mainly composed of proteins, lipids, sugars or polymer compounds. In a specific embodiment, the ultrasonic microbubbles can use targeted nano-scale lipid microbubbles, which are safe, effective, and long-lasting, and can carry genes, drugs, targeting substances, fluorescent proteins, etc. to target and identify specific organs or even specific molecules. The fluorescent substances carried by the microbubbles also help the ultrasonic visualization display system to display and locate the administration site and depth. After the microbubbles are destroyed under ultrasonic irradiation, a large amount of drugs can be released at the lesion site, thereby improving the local efficacy without causing systemic side effects. The therapeutic effect of ultrasound itself combined with the drug effect can improve the efficacy. The nanoformulations developed for transdermal use include polymer nanoparticles, nanogels, nanoemulsions, lipid-based nanoparticles, dendritic molecules, nanocapsules and nanogels. There are many types of existing gas-containing microbubbles. Many drugs have been used for ultrasonic penetration, including hydrocortisone, betamethasone, dipropionic acid, oligodeoxynucleotides, chymosin, dexamethasone, fluocinolone, heparin, hyaluronidase, ibuprofen, indomethacin, insulin, iodine, ketoprofen, lidocaine, methoxy, naproxen, piroxicam, sodium salicylate, trypsin, zinc, etc., as well as some anticancer drugs and thrombolytic drugs. The above drugs can be ultrasonically transdermally administered through the present invention.

[0047] The present invention controls the high-power acoustic radiation force pulse sequence and sharp imaging pulse sequence generated by the transducer through an ultrasonic electronic control system, thereby realizing precise driving of the low-frequency ring array and high-frequency array element of the ultrasonic transducer, and realizing the dynamic output of the lesion area of ​​interest simultaneously or alternately in real time by dual-frequency ultrasound; through the ultrasonic microbubble effect of the ultrasonic microbubble transdermal drug delivery device, ultrasonic treatment and transdermal drug delivery under real-time navigation and monitoring are realized. The ultrasonic visualization monitoring system locates the treatment site and the drug delivery site, and visualizes the environment of the treatment site and the drug delivery site on the system, which plays the role of monitoring and adjusting the treatment plan. The ultrasonic visualization monitoring system is combined with the ultrasonic microbubble transdermal device to achieve precise treatment and ultrasonic permeation directional drug delivery.

[0048] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system, characterized in that: The invention comprises: an ultrasonic transdermal drug delivery system, an ultrasonic visualization monitoring system and an ultrasonic electronic control system. The ultrasonic transdermal drug delivery system comprises: a signal generator, an ultrasonic transducer and an ultrasonic microbubble transdermal drug delivery device; the ultrasonic visualization monitoring system comprises: a time gain compensation circuit, a filter sequence and a power amplifier array, a high-efficiency noise amplifier and an ultrasonic imaging monitoring probe; The output end of the ultrasonic imaging monitoring probe is connected to the input end of the high-efficiency noise amplifier, the output end of the high-efficiency noise amplifier is connected to the time gain compensation circuit through the power amplifier array and the filter sequence in sequence, and the output end of the time gain compensation circuit is connected to the input end of the ultrasonic electronic control system through the AD converter; The output end of the ultrasonic electronic control system is connected to the input end of the signal generator through the main clock and the delay device in sequence, and the output end of the signal generator is connected to the ultrasonic transducer; The ultrasonic electronic control system is used to generate control electrical signals, control the acoustic radiation force pulse sequence and the sharp imaging pulse sequence generated by the ultrasonic transducer, and realize the driving of the low-frequency peripheral annular array element array and the high-frequency central array element of the ultrasonic transducer; The ultrasonic transducer is used to generate low-frequency peripheral annular array element array and high-frequency central array element ultrasonic waves; The ultrasonic microbubble transdermal drug delivery device is used to immerse the ultrasonic transducer in a liquid filled with drug-loaded ultrasonic microbubbles and directly contact and fix it on the skin to achieve transdermal drug delivery; The ultrasonic microbubble transdermal drug delivery device comprises ultrasonic microbubbles, the shell of which comprises one or more of proteins, lipids, sugars or polymer compounds; The ultrasonic visualization monitoring system displays and locates the treatment site, drug delivery site and depth, and achieves precise drug delivery by adjusting the ultrasonic output mode, frequency and intensity, adjusting the drug-loaded ultrasonic microbubble penetration direction, depth, penetration amount and microbubble breaking timing of the ultrasonic microbubble transdermal drug delivery device.

2. A multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system according to claim 1, characterized in that: The ultrasonic transducer is a dual-frequency multi-element 2-ring array ultrasonic transducer. The central operating frequency of the middle element of the dual-frequency multi-element 2-ring array ultrasonic transducer is 1-3MHz, and the operating frequency of the outer ring array elements is set to be greater than 20KHz. The middle element and the outer ring array elements can output synchronously or alternately.

3. A multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system according to claim 2, characterized in that: The peripheral ring array elements of the dual-frequency multi-element 2-ring array ultrasonic transducer work simultaneously and emit ultrasonic waves a and b focused at the same position, wherein the frequency of ultrasonic wave a is >20KHz, and the frequency of ultrasonic wave b is 1-3MHz.

4. The multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system according to claim 2, characterized in that: The power of ultrasound between different array elements is adjustable within a set range, and pulse or continuous ultrasound can be set.

5. The multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system according to claim 1, characterized in that: The transmitting circuit of the ultrasonic electronic control system can control the gating or closing of each transmitting channel, and can configure control parameters, which include: configuring the transmitting pulse frequency, transmitting pulse amplitude, and transmitting mode.

6. The multi-frequency and multi-power ultrasonic microbubble non-invasive transdermal drug delivery treatment and real-time ultrasonic visualization monitoring system according to claim 1, characterized in that: The ultrasonic microbubble transdermal drug delivery device is used for transdermal drug delivery in cooperation with the probe of an ultrasonic transducer; the ultrasonic microbubble transdermal drug delivery device comprises: a circular plastic shell, the interior of the circular plastic shell is a drug-carrying cavity; a first circular hole and a second circular hole are provided on the upper part of the drug-carrying cavity, the diameter of the first circular hole is greater than the diameter of the second circular hole, the first circular hole is connected to the ultrasonic transducer, and the second circular hole is used for injecting drug liquid; the microbubbles of the ultrasonic microbubble transdermal drug delivery device are placed in the drug-carrying cavity; the circular opening below the drug-carrying cavity is directly adhered to the skin, and a waterproof skin patch is surrounded below the shell for adhering the ultrasonic microbubble transdermal drug delivery device to the skin; water or drug solution is injected into the drug-carrying cavity through the second circular hole of the drug-carrying cavity, the water or drug solution is fully mixed with the ultrasonic microbubbles, and can be used as a coupling agent between the ultrasonic transducer probe and the skin, and at the same time as a carrier of the drug to be introduced.

Images