Negative pressure synergized jet transdermal delivery device

Abstract

The application provides a negative pressure and jet transdermal delivery device, an execution end comprises an end body, the end body is provided with a negative pressure cavity, the inside of the negative pressure cavity is provided with a jet part, the jet part is provided with a jet port, a negative pressure processing module comprises a negative pressure source, the negative pressure source is communicated with the negative pressure cavity, a jet driving module comprises a pressure source, the pressure source is communicated with the jet port of the jet part, and a liquid medicine supply module is communicated with the jet driving module. By setting the jet part in the negative pressure cavity, the area affected by the negative pressure and the area affected by the jet overlap in space. When the negative pressure processing module applies controllable negative pressure to the target area, the synergy of negative pressure pretreatment and jet active delivery can be achieved. Controllable negative pressure is applied to the skin before or during the delivery of the liquid medicine jet, the skin is reversibly pre-deformed locally, and then the liquid medicine jet is used to deliver the medicine to the skin tissue layer of the target area, achieving efficient, low-damage and controllable transdermal delivery of macromolecular drugs.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and in particular to a negative pressure synergistic jet transdermal delivery device. Background Technology

[0002] Large molecule drugs such as peptides, proteins, and nucleic acid vaccines have important applications in cancer treatment, infectious disease control, immune modulation, and chronic disease management. However, these drugs typically have large molecular weights, strong hydrophilicity, weak transmembrane transport capabilities, and poor in vivo stability, and their clinical application still mainly relies on injection. Although traditional injection methods have high delivery efficiency, they also present problems such as pain, trauma, and infection risks. Transdermal drug delivery avoids the trauma and pain associated with traditional injections and offers advantages such as ease of use, high patient compliance, and suitability for long-term or repeated administration. However, the stratum corneum, epidermal-dermal junction, and superficial dermis constitute multiple physical barriers that severely limit the transdermal transport of large molecule drugs.

[0003] Existing transdermal penetration enhancement technologies include chemical penetration enhancers, microneedles, electroporation, ultrasound, thermal penetration enhancement, and needle-free high-pressure jetting. Among these, chemical penetration enhancers may cause skin irritation and drug inactivation; microneedles may have issues such as needle residue, complex preparation, and dosage limitations; electroporation and ultrasound are complex and require high parameter control; while traditional needle-free jetting can achieve active penetration, it often relies on high jet pressure, which can easily cause local tissue damage, uneven deposition distribution, or difficulty in precisely controlling the delivery depth.

[0004] Therefore, improving the transdermal delivery of macromolecular drugs is a technical problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0005] Therefore, it is necessary to provide a negative pressure synergistic jet transdermal delivery device to address the aforementioned technical problems.

[0006] This application provides a negative pressure synergistic jet transdermal delivery device, the negative pressure synergistic jet transdermal delivery device comprising:

[0007] The execution end includes an end body, the end body is provided with a negative pressure chamber, the negative pressure chamber is provided with a jetting element, and the jetting element is provided with a jetting port;

[0008] A negative pressure processing module, the negative pressure processing module including a negative pressure source, the negative pressure source being connected to the negative pressure chamber;

[0009] A jet driving module, the jet driving module including a pressure source, the pressure source being connected to the jet port of the jet element;

[0010] A drug supply module, which is connected to the jet driving module, is used to store the drug to be delivered and supply the drug to the jet driving module.

[0011] In one embodiment, the end body is further provided with a sealing structure; and / or,

[0012] The negative pressure treatment module further includes a negative pressure regulating valve assembly; and / or,

[0013] The jet drive module further includes a jet modulation valve assembly; and / or,

[0014] The negative pressure source is connected to the negative pressure chamber via a negative pressure pipeline; and / or,

[0015] The pressure source is connected to the jetting device via a liquid pipeline.

[0016] In one embodiment, the negative pressure synergistic jet transdermal delivery device includes:

[0017] A sensing module, wherein the sensing module is disposed on at least one of the end body, the negative pressure pipeline, and the drug solution pipeline, is used to collect at least one of the negative pressure signal, the jet pressure signal, and the adhesion status signal; and

[0018] The control module is connected to the negative pressure regulating valve group, the jet modulation valve group and the sensing and detection module for data communication.

[0019] The control module includes a parameter setting unit, a timing control unit, and a comparison and adjustment unit. The comparison and adjustment unit is connected to the sensing and detection module, the parameter setting unit, and the timing control unit.

[0020] In one embodiment, the timing control unit of the control module has a variety of preset timing programs built in, and the variety of preset timing programs includes at least one of the following:

[0021] A first timing program is configured to control the negative pressure regulating valve group to open before the jet modulation valve group, and to open the jet modulation valve group after the negative pressure processing module has completed the negative pressure pretreatment.

[0022] A second timing program is configured to control the negative pressure regulating valve group to remain in the open state while the jet modulation valve group is intermittently opened;

[0023] The third timing program is configured to control the negative pressure regulating valve group and the jet modulation valve group to open alternately according to a preset cycle.

[0024] In one embodiment, the sensing module includes at least one of a negative pressure sensor, a jet pressure sensor, a flow sensor, and a displacement sensor; wherein:

[0025] The negative pressure sensor is disposed in the negative pressure pipeline or the negative pressure chamber;

[0026] The jet pressure sensor is installed in the drug solution pipeline or the jet component;

[0027] The flow sensor is installed in the drug solution pipeline;

[0028] The displacement sensor is disposed on the end body.

[0029] In one embodiment, the sealing structure is fixed to the mating end face of the end body, the mating end face of the end body being configured to contact the target area;

[0030] At least a portion of the sealing structure protrudes from the mating end face of the end body to form a sealing contact with target areas of different curvatures.

[0031] In one embodiment, the execution end further includes a sterile contact element, which includes an annular sealing fitting portion and a sterile nozzle channel portion. The annular sealing fitting portion is connected to the sealing structure, and the sterile nozzle channel portion is connected to the jet element. The sterile nozzle channel portion is also detachably connected to the drug solution pipeline.

[0032] In one embodiment, the execution end further includes an adjustment mechanism disposed between the jetting element and the end body, the adjustment mechanism being used to adjust the position of the jetting orifice of the jetting element inside the negative pressure chamber; and / or,

[0033] The jet nozzle of the jetting component includes multiple micro-nozzles, which are arranged in at least one of a circular array or a rectangular array.

[0034] In one embodiment, the execution end further includes an anti-backflow structure disposed at the inflow end of the jet element.

[0035] In one embodiment, the negative pressure value within the negative pressure chamber is reduced by 5 kPa to 80 kPa relative to atmospheric pressure; and / or,

[0036] The pulse width output by the jet device is from 1ms to 1000ms; and / or,

[0037] The jet output frequency of the pulse jet from the jetting element is from 0.05 Hz to 50 Hz; and / or,

[0038] The pressure source outputs a pressure value of 0.05 MPa to 30 MPa; and / or,

[0039] The negative pressure source is a miniature vacuum pump, a negative pressure pump, a syringe-type negative pressure generator, or a Venturi negative pressure generator; and / or,

[0040] The pressure source is a pneumatic drive assembly, a mechanical spring drive assembly, a piezoelectric drive assembly, an electromagnetic drive assembly, a diaphragm pump drive assembly, or a plunger pump drive assembly.

[0041] In the aforementioned negative pressure synergistic jet transdermal delivery device, by placing the jet component inside the negative pressure chamber, the area where negative pressure can act and the area where the jet can act spatially overlap, or at least partially overlap, with each other. When the negative pressure treatment module applies controllable negative pressure to the target area (i.e., the skin), it controls the target area to undergo pre-deformation, thereby achieving a synergistic effect between negative pressure pretreatment and active jet delivery. Therefore, by applying controllable negative pressure to the skin before or during drug jet delivery, causing reversible pre-deformation of the local skin, and then using the drug jet to deliver the drug to the skin tissue layer of the target area, efficient, low-damage, and controllable transdermal delivery of macromolecular drugs can be achieved. Attached Figure Description

[0042] Figure 1 This is a schematic diagram of the structure of a negative pressure synergistic jet transdermal delivery device provided in one embodiment of this application.

[0043] Figure 2 This is a schematic diagram of the execution terminal provided in one embodiment of this application.

[0044] Figure 3 This is a schematic diagram of the initial attachment state of the execution end provided in one embodiment of this application.

[0045] Figure 4 This is a schematic diagram of the negative pressure processing state at the execution end provided in one embodiment of this application.

[0046] Figure 5 This is a schematic diagram of the jet delivery state at the execution end provided in one embodiment of this application.

[0047] Figure 6 This is a schematic diagram of the drug deposition state at the execution end provided in one embodiment of this application.

[0048] Figure 7 The timing control diagram of negative pressure and jet parameters is provided for one embodiment of this application.

[0049] Figure 8 This is a multi-mode delivery flowchart provided for one embodiment of this application.

[0050] Figure 9This is a feedback control flowchart provided for one embodiment of this application.

[0051] Icon labels:

[0052] 10. Target area; 20. Liquid jet;

[0053] 100. Execution end; 200. Negative pressure processing module; 300. Jet drive module; 400. Liquid supply module; 500. Sensing and detection module; 600. Control module; 700. Power supply module;

[0054] 110. Terminal body; 120. Negative pressure chamber; 130. Jet component; 140. Sealing structure; 150. Adjustment mechanism; 160. Anti-backflow structure;

[0055] 131. Jet port. Detailed Implementation

[0056] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0057] In the description of this application, it should be understood that if terms such as "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential" appear, these terms indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0058] Furthermore, where the terms "first" and "second" appear, these terms are for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined with "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, where the term "multiple" appears, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0059] In this application, unless otherwise expressly specified and limited, the terms "installation," "connection," "joining," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise expressly limited. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0060] In this application, unless otherwise expressly specified and limited, the use of descriptions such as "above" or "below" the second feature indicates that the first and second features are in direct contact or indirect contact via an intermediate medium. Furthermore, "above," "on top of," and "over" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. Similarly, "below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0061] It should be noted that if an element is referred to as being "fixed to" or "set on" another element, it can be directly on the other element or there may be an intervening element. If an element is considered to be "connected to" another element, it can be directly connected to the other element or there may be an intervening element. If so, the terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this application are for illustrative purposes only and do not represent the only possible implementation.

[0062] See Figures 1 to 9 As shown, this application provides a negative pressure synergistic jet transdermal delivery device, which includes an actuator 100, a negative pressure processing module 200, a jet driving module 300, and a drug supply module 400. The actuator 100 includes an actuator body 110, which has a negative pressure chamber 120. A jet element 130 is disposed inside the negative pressure chamber 120, and the jet element 130 has a jet port 131. The negative pressure processing module 200 includes a negative pressure source, which is connected to the negative pressure chamber 120. The jet driving module 300 includes a pressure source, which is connected to the jet port 131 of the jet element 130. The drug supply module 400 is connected to the jet driving module 300 and is used to store the drug to be delivered and supply the drug to the jet driving module 300.

[0063] The drug solution to be delivered may include, but is not limited to, peptides, proteins, antibodies, nucleic acids, mRNA, siRNA, DNA, vaccine antigens, immunomodulators, nanomedicines, cytokines, hormonal drugs, local anesthetics, anti-inflammatory drugs, and metabolic regulators. Those skilled in the art can select the type of drug solution according to actual needs, and no limitation is made herein.

[0064] The end effector 100 is a component in a negative pressure synergistic jet transdermal delivery device used to directly contact the target area 10 (i.e., the skin) and achieve negative pressure loading and jet output. The end body 110 can be used to construct the negative pressure chamber 120, carry the jet component 130 and various tubing interfaces. The end body 110 can be made of medical polymer materials such as polycarbonate, polyetheretherketone, polypropylene, polysulfone, etc., or metal materials such as stainless steel, titanium alloy, aluminum alloy, etc., or ceramic materials or their composite materials.

[0065] The negative pressure chamber 120 can be located on the skin-closed side of the end body 110, and is used to jointly define a local sealed space after contacting the skin surface during operation. The shape of the negative pressure chamber 120 can be cylindrical, conical, hemispherical, frustum-shaped, or irregular cross-sectional shape, etc., and the inner wall surface of the negative pressure chamber 120 can be provided with concave and convex textures or flow guiding structures to improve the uniformity of negative pressure distribution, which is not limited here.

[0066] The jetting element 130 is disposed inside the negative pressure chamber 120. The jetting element 130 can be a tubular structure, a nozzle structure, or a microchannel structure, etc., and is not limited here. The jetting port 131 is disposed at the end of the jetting element 130 and is used to deliver the liquid medicine jet 20 to the target area 10 within the negative pressure chamber 120, i.e., to the skin. The jetting port 131 can be located at the center, off-center, or in a multi-point array position within the negative pressure chamber 120, etc., and is not limited here.

[0067] The negative pressure processing module 200 includes a negative pressure source connected to a negative pressure chamber 120. The negative pressure processing module 200 applies controllable negative pressure to the target area 10 (i.e., skin), thereby controlling the pre-deformation of the target area 10. The negative pressure source can be a miniature vacuum pump, a negative pressure pump, a syringe-type negative pressure generator, a Venturi negative pressure generator, or an external negative pressure interface, etc. The negative pressure source is connected to the negative pressure chamber 120 via a negative pressure pipeline. Furthermore, auxiliary components such as filters, buffer chambers, and valve assemblies can be installed on the negative pressure pipeline as needed; no limitations are specified here.

[0068] The jet drive module 300 includes a pressure source connected to the jet port 131 of the jet component 130. The jet drive module 300 generates a controllable liquid jet 20. The pressure source can be a pneumatic drive assembly, a mechanical spring drive assembly, a piezoelectric drive assembly, an electromagnetic drive assembly, a diaphragm pump drive assembly, or a plunger pump drive assembly, etc. After the pressure source is connected to the jet component 130 via a liquid pipeline, auxiliary components such as check valves, filters, venting structures, and buffer structures can be installed on the liquid pipeline as needed; these are not limited here.

[0069] The drug supply module 400 is connected to the jet driving module 300 and is used to store the drug solution to be delivered and supply it to the jet driving module 300. The drug supply module 400 may include structures such as a drug storage chamber, drug tubing, and drug interface. The drug storage chamber may be a syringe, drug pouch, rigid storage bottle, flexible storage chamber, or microfluidic storage chip, etc. The drug supply module 400 may be equipped with a filter membrane, venting structure, one-way valve, and sterile connection interface to ensure stable drug output and safe use.

[0070] In the aforementioned negative pressure synergistic jet transdermal delivery device, by placing the jet element 130 inside the negative pressure chamber 120, the area where negative pressure can act and the area where the jet can act spatially overlap, or at least partially overlap. When the negative pressure treatment module 200 applies controllable negative pressure to the target area 10 (i.e., the skin), it controls the target area 10 to undergo pre-deformation, thereby achieving a synergistic effect between negative pressure pretreatment and active jet delivery. Therefore, by applying controllable negative pressure to the skin before or during the delivery of the drug jet 20, reversible pre-deformation occurs locally in the skin, and then the drug jet 20 delivers the drug to the skin tissue layer of the target area 10, thereby achieving efficient, low-damage, and controllable transdermal delivery of macromolecular drugs.

[0071] In one embodiment, the distal body 110 may also be provided with a sealing structure 140 as needed. The sealing structure 140 can be used to improve the adhesion stability between the distal body 110 and the skin surface, adapting to different skin curvatures and surface microtextures. The sealing structure 140 can be fixed to the mating end face of the distal body 110, which is configured to contact the target area 10. At least a portion of the sealing structure 140 protrudes from the mating end face of the distal body 110 to form a sealed contact with the target area 10 with different curvatures. The sealing structure 140 may be an annular sealing ring, a flexible skirt, a gel sealing layer, a medical silicone sealing pad, a hydrogel adhesive layer, or a combination thereof. The sealing structure 140 may be made of flexible materials such as medical silicone rubber, thermoplastic elastomer, polyurethane, or hydrogel. The shape of the sealing structure 140 can be adapted to the anatomical features of different skin areas. For example, a planar annular sealing structure 140 can be used for flat areas such as the forearm and abdomen, while an arc-shaped or contoured sealing structure 140 can be used for curved areas such as the thigh and upper arm.

[0072] The negative pressure processing module 200 may further include a negative pressure regulating valve assembly, which can be used to regulate the pressure magnitude and rate of change within the negative pressure chamber 120. The negative pressure regulating valve assembly may include one or more of the following: a solenoid valve, a proportional valve, a pressure relief valve, a pressure stabilizing chamber, and a filter unit. For example, a solenoid valve can be used to achieve rapid switching of negative pressure on and off; a proportional valve can be used to achieve continuous and precise adjustment of negative pressure intensity; a pressure relief valve can be used to quickly release negative pressure in abnormal situations or after delivery to avoid excessive stretching of the skin; a pressure stabilizing chamber can be used to buffer negative pressure fluctuations and improve negative pressure stability; and a filter unit can be used to prevent particles or contaminants from entering the negative pressure pipeline and the negative pressure chamber 120. Therefore, the opening and closing of the valves in the negative pressure regulating valve assembly can be adjusted according to the target negative pressure value and sensor feedback signals to create a stable or dynamically changing negative pressure within the negative pressure chamber 120.

[0073] The jet drive module 300 also includes a jet modulation valve assembly, which can be used to modulate the jet pressure, pulse width, injection frequency, and number of injections. The jet modulation valve assembly may include one or more of a high-speed solenoid valve, piezoelectric valve, microfluidic valve, pressure regulating valve, or pulse controller. For example, a high-speed solenoid valve can achieve rapid switching at the millisecond or even microsecond level, thereby generating a high-frequency pulsed jet; a piezoelectric valve has a fast response speed and high control accuracy, suitable for small-dose precision delivery; a microfluidic valve can achieve precise control of minute flow rates; a pressure regulating valve can be used to adjust the magnitude of the jet drive pressure; and a pulse controller can be used to set timing parameters such as pulse width, pulse interval, and number of pulses. Through the jet modulation valve assembly, the jet can be designed as a single-pulse jet, a multi-pulse jet, a continuous jet, or an intermittent jet, depending on the requirements.

[0074] The negative pressure source is connected to the negative pressure chamber 120 via a negative pressure pipeline. This pipeline can be medical-grade flexible or rigid, and the materials used can include silicone rubber, polyvinyl chloride, polyurethane, polytetrafluoroethylene, or stainless steel. Auxiliary components such as filters, buffer chambers, valve assemblies, and sensor interfaces can be installed on the negative pressure pipeline. For example, filters can prevent particles from entering the negative pressure source; buffer chambers can absorb negative pressure fluctuations and improve negative pressure stability; valve assemblies can control the on / off state and magnitude of the negative pressure; and sensor interfaces can be used to install negative pressure sensors.

[0075] The pressure source is connected to the jetting element 130 via a drug solution pipeline. This pipeline can be medical-grade flexible or rigid, and the pipeline material should have good biocompatibility and corrosion resistance; for example, silicone rubber, polyvinyl chloride, polyurethane, polytetrafluoroethylene, or stainless steel can be used. The drug solution pipeline can be equipped with a check valve, filter, venting structure, flow sensor, and pressure sensor. For example, the check valve can prevent drug backflow; the filter can remove particles and air bubbles from the drug solution; the venting structure can discharge gas from the pipeline to prevent gas from entering the jetting element 130 and affecting the jet quality; the flow sensor can detect the drug flow rate; and the pressure sensor can detect the jet pressure.

[0076] In one embodiment, the negative pressure synergistic jet transdermal delivery device may further include functional modules such as a sensing module 500, a control module 600, and a power module 700. The sensing module 500 is disposed on at least one of the end body 110, the negative pressure pipeline, and the drug solution pipeline, and is used to collect at least one of the negative pressure signal, the jet pressure signal, and the adhesion status signal. The control module 600 is connected to the negative pressure regulating valve group, the jet modulation valve group, and the sensing module 500 for data communication; wherein, the control module 600 has a built-in parameter setting unit, a timing control unit, and a comparison and adjustment unit, and the comparison and adjustment unit is connected to the sensing module 500, the parameter setting unit, and the timing control unit. The power module 700 can be used to supply power to the negative pressure synergistic jet transdermal delivery device.

[0077] The sensing and detection module 500 may include one or more of the following: a negative pressure sensor, a jet pressure sensor, a flow sensor, a displacement sensor, an optical detection unit, a contact pressure sensor, and a leakage detection unit. The negative pressure sensor can be used to detect the pressure in the negative pressure chamber 120 or negative pressure pipeline in real time, and can be a piezoresistive pressure sensor, a capacitive pressure sensor, or a piezoelectric pressure sensor. The jet pressure sensor can be used to detect the jet pressure in the drug pipeline or jetting device 130, and can be a high-frequency response dynamic pressure sensor. The flow sensor can be used to detect the drug flow rate in the drug pipeline, and can be a thermal flow sensor, an ultrasonic flow sensor, or a mechanical flow sensor. The displacement sensor can be used to detect the amount of skin pre-deformation, such as the height of skin bulges, and can be a laser displacement sensor, an ultrasonic displacement sensor, a capacitive displacement sensor, or a resistive displacement sensor. The optical detection unit can be used to detect the contact state of the actuator end 100, and can be an image sensor or a photoelectric sensor. The contact pressure sensor can be used to detect the contact pressure between the actuator end 100 and the skin. The leak detection unit can be used to detect the sealing status of the negative pressure chamber 120, and can determine whether there is a leak by monitoring the pressure drop rate during the negative pressure maintenance period.

[0078] The control module 600 may include a microcontroller, embedded processor, programmable logic controller, drive circuit, human-machine interface, and communication module. The control module 600 integrates a parameter setting unit, a timing control unit, and a comparison and adjustment unit. The comparison and adjustment unit is connected to the sensing module 500, the parameter setting unit, and the timing control unit. The parameter setting unit can receive user-inputted or preset negative pressure and jet parameters, including negative pressure intensity, negative pressure duration, jet pressure, pulse width, jet frequency, number of jets, and delivery dose. The timing control unit can store and execute various preset timing programs to control the timing relationship between negative pressure pretreatment and jet delivery. The comparison and adjustment unit can compare the real-time signal acquired by the sensing module 500 with the target value in the parameter setting unit, and generate an adjustment signal based on the comparison result to control the operation of the negative pressure regulating valve group and the jet modulation valve group, achieving closed-loop control.

[0079] In one embodiment, the timing control unit of the control module 600 has a variety of preset timing programs (or modes) built in, and the variety of preset timing programs includes at least one of the following:

[0080] The first timing sequence is configured to control the negative pressure regulating valve group to open before the jet modulation valve group, and to open the jet modulation valve group only after the negative pressure processing module 200 has completed the negative pressure pretreatment. Under this first timing sequence, negative pressure is first applied to the skin for negative pressure pretreatment, causing pre-deformation of the skin. After the skin pre-deformation reaches the preset conditions, the negative pressure can be released or partially maintained, and then the jet drive module 300 is activated to output the drug jet 20. This mode is suitable for scenarios where the skin is sensitive to irritation or where a reduction in jet pressure is required. The negative pressure pretreatment time can be set according to the skin location, tissue characteristics, and drug type, for example, it can be set from 1 second to 600 seconds.

[0081] The second timing sequence is configured to control the jet modulation valve group to open intermittently while maintaining the negative pressure regulating valve group in an open state. Under this second timing sequence, the negative pressure is continuously maintained throughout the drug delivery process, keeping the skin in a pre-deformed state at all times. While maintaining the negative pressure, the jet drive module 300 intermittently outputs jets according to preset pulse parameters, causing multiple jet pulses to act on the same pre-deformed skin area. This mode is beneficial for improving delivery depth and deposition distribution uniformity, and is suitable for scenarios requiring larger doses or deeper delivery. The negative pressure maintenance time can be set as needed, the jet pulse width can range from 1 millisecond to 1000 milliseconds, and the pulse interval can range from 0.02 seconds to 20 seconds.

[0082] The third timing sequence is configured to control the alternating opening of the negative pressure regulating valve group and the jet modulation valve group according to a preset cycle. Under this third timing sequence, it can operate in a cyclical pattern of negative pressure loading, jet output, tissue recovery, re-negative pressure loading, re-jet output, and so on. For example, after 10 seconds of negative pressure loading, a pulse jet is output, followed by a 20-second tissue recovery period, after which the above cycle is repeated. This mode is suitable for drugs requiring fractionated, low-dose, and low-irritation delivery, reducing tissue damage caused by a single high-pressure jet. The specific cycle can be repeated 2 to 10 times or more, depending on the drug dosage and treatment plan, and is not limited here.

[0083] In one embodiment, the sensing module 500 includes at least one of a negative pressure sensor, a jet pressure sensor, a flow sensor, and a displacement sensor. The negative pressure sensor is disposed in a negative pressure pipeline or negative pressure chamber 120. The negative pressure sensor can be used to detect the pressure value in the negative pressure chamber 120 or negative pressure pipeline in real time and transmit the pressure signal to the control module 600. The negative pressure sensor can be a piezoresistive pressure sensor, a capacitive pressure sensor, or a piezoelectric pressure sensor. The range of the negative pressure sensor can be selected according to the negative pressure operating range; for example, a sensor with a range of -100 kPa to 0 kPa can be selected. The control module 600 determines whether the negative pressure has reached a preset value based on the feedback signal from the negative pressure sensor and automatically adjusts the negative pressure source or negative pressure regulating valve assembly for compensation when the pressure deviates.

[0084] A jet pressure sensor is installed in the liquid pipeline or jetting device 130. The jet pressure sensor can be used to detect the jet pressure value in the liquid pipeline or jetting device 130 in real time and transmit the corresponding pressure signal to the control module 600. The jet pressure sensor can be a high-frequency response dynamic pressure sensor to adapt to the rapid pressure changes of the pulsed jet. The range of the jet pressure sensor can be selected according to the jet's operating range; for example, a sensor with a range of 0 to 50 MPa can be selected. The control module 600 can be used to determine whether the jet pressure has reached a preset value based on the pressure signal fed back by the jet pressure sensor, and adjust the pressure source or pause the jet output when the pressure is abnormal.

[0085] A flow sensor is installed in the drug delivery line. The flow sensor can be used to detect the flow rate of the drug in the line in real time and transmit the flow signal to the control module 600. The flow sensor can be a thermal flow sensor, ultrasonic flow sensor, mechanical flow sensor, or mass flow sensor. The control module 600 can calculate the cumulative delivery dose based on the flow signal fed back from the flow sensor and stop the jet output when the preset dose is reached. The flow sensor can also be used to detect abnormalities such as drug blockage or line leakage.

[0086] A displacement sensor is installed on the end body 110. The displacement sensor can be used to detect the amount of pre-deformation of the skin under negative pressure in real time, such as the height of skin elevation or the distance of skin displacement. The displacement sensor can be a laser displacement sensor, ultrasonic displacement sensor, capacitive displacement sensor, resistive displacement sensor, or optical image sensor. The displacement sensor can be installed at a suitable location, such as the inner wall of the end body 110, inside the negative pressure chamber 120, or on the outer side of the end body 110. The control module 600 can be used to determine whether the skin pre-deformation has reached the preset condition based on the pre-deformation signal fed back by the displacement sensor, and to extend the negative pressure time or increase the negative pressure intensity when the skin deformation is insufficient, and to reduce the negative pressure or stop the operation when the skin deformation exceeds a safety threshold.

[0087] In one embodiment, the sealing structure 140 is fixed to the mating end face of the end body 110, which is configured to contact the target area 10. At least a portion of the sealing structure 140 protrudes from the mating end face of the end body 110 to form a sealing contact with the target area 10, which has different curvatures. The height of the sealing structure 140 protruding from the mating end face can be determined based on skin elasticity and the required sealing pressure; for example, the protrusion height can be designed to range from 0.5 mm to 10 mm. The sealing structure 140 can be in the form of an annular sealing ring, arranged around the opening edge of the negative pressure chamber 120. The sealing structure 140 can also be in the form of a flexible skirt extending outward along the opening edge of the negative pressure chamber 120 to form a larger sealing contact area. The sealing structure 140 can also be in the form of a gel sealing layer, which can adaptively fill the micro-textures of the skin surface to improve the sealing effect.

[0088] The sealing structure 140 can be made of medical-grade silicone rubber, thermoplastic elastomer, polyurethane, hydrogel, or a combination thereof. Medical-grade silicone rubber has good flexibility, biocompatibility, and aging resistance. Thermoplastic elastomers have excellent elasticity and processability. Polyurethane has good abrasion resistance and tear resistance. Hydrogel has good biocompatibility and skin adhesion, which can further improve the sealing effect and user comfort.

[0089] Furthermore, the sealing structure 140 can be designed as a detachable and replaceable structure to facilitate cleaning, disinfection, or single-use. The sealing structure 140 can be fixed to the end body 110 by snap-fit ​​connection, threaded connection, or adhesive bonding. The shape and size of the sealing structure 140 can be adapted to different skin areas to form a dedicated sealing structure 140 for different areas.

[0090] In one embodiment, the actuator 100 further includes a sterile contact element comprising an annular sealing fit and a sterile nozzle channel. The annular sealing fit is connected to the sealing structure 140 for forming a sealed contact with the skin surface. The shape of the annular sealing fit may match the sealing structure 140, for example, it may be annular, elliptical, or irregular. The annular sealing fit may be made of a flexible material capable of adapting to the curvature variations of different skin areas. The annular sealing fit may cover all or part of the surface of the sealing structure 140, or it may serve as an extension of the sealing structure 140.

[0091] The sterile nozzle channel is connected to the jet component 130, and is detachably connected to the drug supply line. The sterile nozzle channel guides the drug supply from the drug supply line to the jet nozzle 131, and ultimately outputs it to the target area 10. A drug flow channel can be provided inside the sterile nozzle channel; the shape and size of the flow channel can be designed according to the jet parameters. The sterile nozzle channel and the drug supply line can be detachably connected using methods such as plug-in connection, threaded connection, or snap-fit ​​connection.

[0092] The sterile contact can be a single-use component, which can be disassembled and replaced as a whole after use. The sterile contact can be made of medical-grade materials, such as medical-grade polypropylene, polycarbonate, polyetheretherketone, and medical-grade silicone rubber. The sterile contact can undergo sterilization treatment, such as ethylene oxide sterilization, irradiation sterilization, or high-temperature and high-pressure sterilization, to ensure a sterile state during use. The sterile contact can be individually packaged; it should be removed from the sterile packaging and installed at the execution end 100 before use.

[0093] The end effector 100 also includes an adjustment mechanism 150, which is disposed between the jetting element 130 and the end body 110. The adjustment mechanism 150 is used to adjust the position of the jet outlet 131 of the jetting element 130 within the negative pressure chamber 120. For example, in one embodiment, the adjustment mechanism 150 can be used to adjust the distance between the jet outlet 131 and the skin surface. This distance can affect the jet delivery effect; different distances will affect the speed, diameter, and impact energy of the jet when it reaches the skin. The adjustment range of the adjustment mechanism 150 can be set as needed, for example, from 0.5 mm to 20 mm. The adjustment mechanism 150 can be made of medical-grade metal or polymer materials. The adjustment mechanism 150 can be implemented using a limiting ring, an adjustable bracket, an elastic support, a threaded adjustment structure, or a replaceable gasket.

[0094] For example, a limiting ring can be disposed on the outer periphery of the jet element 130. By changing the limiting rings of different thicknesses, the length of the jet element 130 extending out of the negative pressure chamber 120 can be changed, thereby adjusting the distance between the jet port 131 and the skin surface. An adjustable bracket may include multiple hinged or slidingly connected support arms. The position of the jet element 130 can be changed by adjusting the angle or position of the support arms. An elastic support member can be disposed between the jet element 130 and the end body 110, utilizing the deformation of the elastic element to achieve fine-tuning of the position of the jet element 130. A threaded adjustment structure can be provided between the jet element 130 and the end body 110, allowing the axial position of the jet element 130 to be changed by rotating it. A replaceable shim can be disposed between the jet element 130 and the end body 110, allowing the position of the jet element 130 to be adjusted by changing the shims of different thicknesses.

[0095] The jet nozzle 131 of the jetting element 130 includes multiple micro-nozzles, which are arranged in at least one of a ring array or a rectangular array. For example, the multiple micro-nozzles may be located within the negative pressure chamber 120 and distributed around the center of the negative pressure chamber 120, or arranged along the long axis of the negative pressure chamber 120, or arranged in a ring array, rectangular array, honeycomb array, or radial array, without limitation. The number of multiple micro-nozzles can range from 2 to 100. The diameter of each micro-nozzle can range from 10 micrometers to 500 micrometers. The multiple micro-nozzles can have the same or different diameters to meet different delivery requirements.

[0096] The control module 600 can control multiple micro-nozzles to spray simultaneously or in stages to adapt to different skin delivery areas. Simultaneous spraying can deliver drugs simultaneously over a large skin area, improving delivery efficiency. Staged spraying can sequentially open micro-nozzles at different positions according to a preset order, enabling the spatial distribution control of the drug within the skin tissue.

[0097] In one embodiment, the execution end 100 further includes an anti-backflow structure 160, which is disposed at the inflow end of the jet member 130. The anti-backflow structure 160 can be used to reduce liquid backflow or contamination, ensuring the unidirectionality and stability of the jet output. The anti-backflow structure 160 may include a one-way valve, an anti-backflow structure, or a hydrophobic / hydrophilic interface structure, etc.

[0098] For example, a check valve can be installed at the inlet end of the jet element 130, allowing the liquid medicine to flow from the liquid medicine pipeline towards the jet port 131, while preventing the liquid medicine from flowing back from the jet port 131 towards the liquid medicine pipeline. The check valve can be a spring-loaded check valve, a ball-loaded check valve, a diaphragm-loaded check valve, or a duckbill-loaded check valve. A spring-loaded check valve uses spring force to reset the valve core; the valve core opens when the forward pressure exceeds the spring force and closes when there is reverse pressure. A ball-loaded check valve uses the rolling of a ball on the valve seat to achieve unidirectional flow. A diaphragm-loaded check valve uses the deformation of an elastic diaphragm to achieve unidirectional flow. A duckbill-loaded check valve uses the elastic deformation of a duckbill-shaped structure to achieve unidirectional flow.

[0099] For example, an anti-backflow structure can be installed at the inlet end of the jet component 130 to prevent the liquid from being drawn back due to negative pressure after the jetting process. The anti-backflow structure can be an elastic diaphragm or a flexible valve that automatically closes the flow channel when the jet pressure disappears. Another example is a hydrophobic / hydrophilic interface structure that utilizes surface tension to achieve unidirectional flow. Hydrophobic and hydrophilic regions are provided within the flow channel, and the surface tension difference between these regions is used to guide the unidirectional flow of the liquid. Those skilled in the art can design such structures according to actual needs, and no limitations are imposed here.

[0100] In one embodiment, the negative pressure value within the negative pressure chamber 120 is reduced by 5 kPa to 80 kPa relative to atmospheric pressure. The negative pressure intensity can be adjusted based on the skin location, tissue thickness, and safety threshold. For thinner skin areas such as the forearm and back of the hand, a lower negative pressure intensity can be used, for example, a reduction of 5 kPa to 30 kPa relative to atmospheric pressure. For thicker skin areas such as the back and thighs, a higher negative pressure intensity can be used, for example, a reduction of 30 kPa to 60 kPa relative to atmospheric pressure. For scenarios requiring greater pre-deformation, an even higher negative pressure intensity can be used, for example, a reduction of 60 kPa to 80 kPa relative to atmospheric pressure.

[0101] The pulse width output by the jet device 130 ranges from 1 ms to 1000 ms. Here, pulse width refers to the duration of a single jet pulse. Shorter pulse widths, such as 1 ms to 50 ms, are suitable for small-dose, shallow delivery, reducing tissue impact. Longer pulse widths, such as 50 ms to 300 ms, are suitable for large-dose, deep delivery, enabling deeper drug deposition.

[0102] The pulse jet output by the jetting device 130 has a jet frequency ranging from 0.05 Hz to 50 Hz. The jet frequency refers to the number of jet pulses per unit time. Lower jet frequencies, such as 0.05 Hz to 1 Hz, are suitable for single or small-pulse delivery, with a longer tissue recovery time between each pulse. Higher jet frequencies, such as 1 Hz to 50 Hz, are suitable for rapid delivery of multiple pulses, allowing drug administration to be completed in a shorter time.

[0103] The pressure output of the pressure source ranges from 0.05 MPa to 30 MPa. The jet driving pressure is a key parameter affecting jet velocity and delivery depth. Lower driving pressures, such as 0.05 MPa to 1 MPa, are suitable for superficial delivery or pressure-sensitive drugs. Medium driving pressures, such as 1 MPa to 10 MPa, are suitable for routine transdermal delivery. Higher driving pressures, such as 10 MPa to 30 MPa, are suitable for deep delivery or penetration of thicker skin tissue.

[0104] The negative pressure source can be a miniature vacuum pump, a negative pressure pump, a syringe-type negative pressure generator, or a Venturi negative pressure generator. Among these, the miniature vacuum pump is small in size and lightweight. The negative pressure pump provides a stable and controllable negative pressure output. The syringe-type negative pressure generator generates negative pressure by pulling a syringe piston; it is simple in structure and inexpensive. The Venturi negative pressure generator utilizes the negative pressure effect created when compressed air passes through a Venturi tube to generate negative pressure, eliminating the need for an additional negative pressure pump.

[0105] The pressure source can be a pneumatic drive assembly, a mechanical spring drive assembly, a piezoelectric drive assembly, an electromagnetic drive assembly, a diaphragm pump drive assembly, or a plunger pump drive assembly. Among them, the pneumatic drive assembly uses compressed gas to push a piston or diaphragm, ejecting the liquid medicine from the reservoir to form a jet. The mechanical spring drive assembly uses the elastic potential energy of a compressed spring to push a piston, ejecting the liquid medicine to form a jet. The piezoelectric drive assembly uses the inverse piezoelectric effect of a piezoelectric element to generate micro-displacement, pushing a diaphragm or piston to eject the liquid medicine to form a jet, featuring fast response and high control precision. The electromagnetic drive assembly uses electromagnetic force to push a piston or diaphragm, ejecting the liquid medicine to form a jet. The diaphragm pump drive assembly uses the reciprocating motion of a diaphragm to pump the liquid medicine from the reservoir to form a jet. The plunger pump drive assembly uses the reciprocating motion of a plunger to eject the liquid medicine from the reservoir to form a jet.

[0106] Combination Figures 3 to 6 As shown, Figures 3 to 6 Schematic diagrams of the execution terminal 100 in different operating states are shown. Figure 3 The initial attachment state of the actuator 100 is shown. In this state, the sealing structure 140 of the actuator 100 contacts the skin surface of the target area 10, forming a preliminary seal. At this time, no negative pressure is applied in the negative pressure chamber 120, and the skin is in a naturally relaxed state. The jet outlet 131 of the jetting element 130 maintains a certain initial distance from the skin surface. Figure 4 The diagram illustrates the negative pressure processing state of the execution end 100. In this state, the negative pressure processing module 200 is activated, applying negative pressure to the negative pressure chamber 120. Under the action of negative pressure, the skin in the target area 10 undergoes controllable bulging or pre-deformation into the negative pressure chamber 120. After the skin bulges, the openness of accessory pathways such as hair follicles and sweat gland ducts increases, and the local tissue stress state is adjusted. The negative pressure sensor detects the pressure value within the negative pressure chamber 120 in real time, and the displacement sensor detects the bulge height of the skin in real time. When the skin pre-deformation reaches the preset conditions, the control module 600 confirms that jet delivery can proceed.

[0107] Figure 5 The image shows the jet delivery state of the execution end 100. In this state, the jet drive module 300 is activated, and the drug solution in the drug supply module 400 enters the jet element 130 through the drug solution pipeline under the drive of the pressure source, and is output from the jet port 131 to form a drug solution jet 20. The drug solution jet 20 acts on the skin of the pre-deformed target area 10 to achieve transdermal drug delivery. The jet can be a single pulse jet, a multi-pulse jet, a continuous jet, or an intermittent jet. The jet pressure sensor detects the jet pressure in real time, and the flow sensor detects the drug solution flow rate in real time. Figure 6The image shows the drug deposition state of the execution end 100. In this state, the drug jet 20 has penetrated the skin surface, and the drug is deposited within the target skin tissue layer. Due to the improved skin entry conditions caused by negative pressure pretreatment, subsequent jets can achieve effective delivery at lower pressures, resulting in deeper, more uniform, and more controllable drug deposition within the skin tissue. After delivery is complete, the control module 600 shuts down the jet drive module 300 and slowly releases the negative pressure through the pressure relief valve, allowing the execution end 100 to be removed from the skin surface.

[0108] Combination Figure 7 As shown, the timing control unit of the control module 600 has a variety of preset timing programs built in, which can control the negative pressure pretreatment and jet delivery to work together in accordance with the preset timing.

[0109] In some embodiments, a first timing sequence (which may be referred to as sequential negative pressure-jet delivery) is employed. In this first timing sequence, the control module 600 controls the negative pressure regulating valve group to open before the jet modulation valve group. First, negative pressure is applied to pre-treat the skin; the negative pressure intensity can be 5 kPa to 80 kPa lower than atmospheric pressure, and the negative pressure duration can be 1 second to 600 seconds. After the skin pre-deformation reaches the preset conditions, the jet modulation valve group is then opened to output the jet. The jet driving pressure can be 0.05 MPa to 30 MPa, and the pulse width can be 1 ms to 1000 ms.

[0110] In some embodiments, a second timing sequence (which may be referred to as jet delivery under negative pressure maintenance) is employed. In this second timing sequence, the control module 600 controls the negative pressure regulating valve group to remain open, so that the negative pressure is continuously maintained throughout the delivery process. Under the negative pressure maintenance state, the jet modulation valve group is opened intermittently, outputting multiple pulse jets. For example, the pressure in the negative pressure chamber is adjusted to be 20 kPa lower than the atmospheric pressure and maintained for 30 seconds, and then three pulse jets are output under the negative pressure maintenance state, each pulse width being 50 ms and the pulse interval being 2 seconds. The negative pressure sensor detects the pressure in the negative pressure chamber in real time, and when the pressure fluctuation exceeds a set threshold, the control module automatically compensates for the negative pressure or suspends the jet output.

[0111] In some embodiments, a third timing sequence (which may be referred to as periodic negative pressure-pulse jet delivery) is employed. In this third timing sequence, the control module 600 controls the negative pressure regulating valve group and the jet modulation valve group to open alternately according to a preset cycle. For example, the operation is performed in a cycle of sequentially executing negative pressure loading for 10 seconds, pulse jet once, tissue recovery for 20 seconds, negative pressure loading again for 10 seconds, pulse jet once again, and so on, and the cycle can be repeated 2 to 10 times.

[0112] Combination Figure 8As shown, in Mode 1, the actuator 100 is first attached to the target area 10, i.e., the skin surface, so that the sealing structure 140 forms a sealed contact with the skin surface. Then, the negative pressure processing module 200 is activated to create a preset negative pressure in the negative pressure chamber 120, causing the local skin to undergo controllable pre-deformation under the action of negative pressure. The sealing state of the actuator 100 and the skin pre-deformation state are determined by the negative pressure sensor, displacement sensor, and leakage detection unit to determine whether the preset conditions have been met. After the skin pre-deformation has reached the preset conditions, the negative pressure is released or partially maintained, and then the jet drive module 300 is activated to output the liquid jet 20. This mode is suitable for scenarios where the skin is sensitive to irritation or where it is necessary to reduce the jet pressure.

[0113] In Mode 2, the drug jet 20 can be output under continuous negative pressure, allowing it to directly act on skin tissue in a pre-deformed state and with appendages open. This mode is beneficial for improving delivery depth and uniformity of deposition distribution. In Mode 3, the negative pressure loading, jet output, and tissue recovery process can be repeated according to a preset cycle. This mode is suitable for drugs requiring fractionated, low-dose, and low-irritation delivery, reducing tissue damage caused by single high-pressure jets. In Mode 4, the negative pressure intensity, jet pressure, and number of sprays can be adjusted in real time based on negative pressure, jet pressure, flow rate, or skin deformation signals. This mode is suitable for individualized skin condition adaptation and safety boundary control.

[0114] Combination Figure 9 As shown, during the negative pressure loading process, the negative pressure sensor can be used to collect the pressure signal within the negative pressure chamber 120 in real time, and the displacement sensor can be used to collect the skin elevation height signal in real time. The comparison and adjustment unit of the control module 600 can be used to compare the collected signal with the target value in the parameter setting unit. When the skin elevation height reaches the preset range, the control module 600 starts jet delivery; when the skin elevation is insufficient, the control module 600 extends the negative pressure action time or increases the negative pressure intensity; when the skin elevation exceeds the safety threshold, the control module 600 reduces the negative pressure or stops the operation.

[0115] During jet delivery, a jet pressure sensor can be used to acquire jet pressure signals in real time, and a flow sensor can be used to acquire drug flow signals in real time. When the jet pressure deviates from the preset value, the control module 600 adjusts the pressure source or jet modulation valve assembly for compensation. When the drug flow is abnormal (such as blockage or leakage), the control module 600 suspends jet output and issues an alarm. When the cumulative delivered dose reaches the preset value, the control module 600 stops jet output and releases negative pressure or enters a safe standby state.

[0116] The negative pressure synergistic jet transdermal delivery device provided in this application is specifically suitable for delivering vaccine antigens, nucleic acid vaccines, immunomodulators, or other bioactive substances that can induce immune responses. In addition to the aforementioned physical delivery enhancement function, the negative pressure synergistic jet transdermal delivery device can also provide an auxiliary local immune gain signal to the target area (i.e., the skin) through the synergistic mechanism of negative pressure and jet.

[0117] Specifically, during the delivery process, the controllable negative pressure in the negative pressure chamber 120 can cause the target area 10 (i.e., the skin) to bulge and stretch locally. This can not only open hair follicles, sweat glands, etc. to reduce drug delivery resistance, but also change the physical tension state of the extracellular matrix in the skin tissue.

[0118] Based on this pre-deformation, the transient drug jet 20 triggered by the jet drive module 300 impacts the skin tissue, which is already in a pre-deformed state, in the form of pulses or continuous flow, forming fluid shear force and impact force superimposed on the negative pressure stimulation. Therefore, the combined mechanical stimulation of the above-mentioned negative pressure stretching and jet impact can constitute a dynamic physical signal acting on the local skin tissue microenvironment.

[0119] Under the aforementioned combined mechanical stimulation, stromal cells, resident immune cells, and antigen-presenting cells in the local skin tissue may undergo a certain degree of mechanical response. This can enhance the uptake, retention, and presentation of antigens or immunomodulatory drugs in the local tissue, and may further promote the recruitment of local immune cells, the maturation of dendritic cells, or the formation of subsequent immune responses. Therefore, the negative pressure synergistic jet delivery method of this application can produce an auxiliary local immune enhancement effect on top of the physical delivery enhancement when used for the delivery of vaccine antigens, nucleic acid drugs, or immunomodulators.

[0120] It should be clarified that the aforementioned immune-enhancing effect is an auxiliary biological response generated based on the unique physical working mode of the negative pressure synergistic jet transdermal delivery device of this application. It aims to optimize the local immune microenvironment at a physical level to auxiliaryly enhance the delivery effect of immune-related drugs. This immune-enhancing effect does not replace traditional chemical immunomodulatory methods such as adjuvants, nor is it contingent upon producing a specific therapeutic effect. The negative pressure synergistic jet transdermal delivery device of this application can be used in combination with conventional adjuvants, immunomodulators, or other pharmaceutical preparations to comprehensively optimize the local delivery and immune effects of vaccines or immunotherapeutic drugs.

[0121] The aseptic contact components, anti-backflow structure, sensors, and valve assemblies described in this embodiment are implemented in the same way as in the previous embodiments, and will not be repeated here. The negative pressure synergistic jet transdermal delivery device of this application achieves efficient and low-damage transdermal delivery, and can also provide a physical delivery platform with potential synergistic benefits for immunotherapy and vaccine administration.

[0122] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0123] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A negative pressure synergistic jet transdermal delivery device, characterized in that, The negative pressure synergistic jet transdermal delivery device includes: An execution terminal (100) includes a terminal body (110), the terminal body (110) is provided with a negative pressure chamber (120), the negative pressure chamber (120) is provided with a jetting element (130), and the jetting element (130) is provided with a jetting port (131). A negative pressure processing module (200) includes a negative pressure source, which is connected to the negative pressure chamber (120); A jet driving module (300) includes a pressure source connected to the jet port (131) of the jet component (130); A liquid medicine supply module (400) is connected to the jet driving module (300) and is used to store the liquid medicine to be delivered and supply the liquid medicine to the jet driving module (300).

2. The negative pressure synergistic jet transdermal delivery device according to claim 1, characterized in that, The end body (110) is also provided with a sealing structure (140); and / or, The negative pressure processing module (200) further includes a negative pressure regulating valve assembly; and / or, The jet drive module (300) further includes a jet modulation valve assembly; and / or, The negative pressure source is connected to the negative pressure chamber (120) via a negative pressure pipeline; and / or, The pressure source is connected to the jetting device (130) through a liquid pipeline.

3. The negative pressure synergistic jet transdermal delivery device according to claim 2, characterized in that, The negative pressure synergistic jet transdermal delivery device includes: A sensing module (500), wherein the sensing module (500) is disposed on at least one of the end body (110), the negative pressure pipeline, and the liquid medicine pipeline, and is used to collect at least one of the negative pressure signal, the jet pressure signal, and the adhesion status signal; and The control module (600) is connected to the negative pressure regulating valve group, the jet modulation valve group and the sensing and detection module (500) via data communication. The control module (600) includes a parameter setting unit, a timing control unit, and a comparison and adjustment unit. The comparison and adjustment unit is connected to the sensing and detection module (500), the parameter setting unit, and the timing control unit.

4. The negative pressure synergistic jet transdermal delivery device according to claim 3, characterized in that, The timing control unit of the control module (600) has a variety of preset timing programs built in, and the various preset timing programs include at least one of the following: A first timing program is configured to control the negative pressure regulating valve group to open before the jet modulation valve group, and to open the jet modulation valve group after the negative pressure processing module (200) has completed the negative pressure preprocessing. A second timing program is configured to control the negative pressure regulating valve group to remain in the open state while the jet modulation valve group is intermittently opened; The third timing program is configured to control the negative pressure regulating valve group and the jet modulation valve group to open alternately according to a preset cycle.

5. The negative pressure synergistic jet transdermal delivery device according to claim 3, characterized in that, The sensing module (500) includes at least one of a negative pressure sensor, a jet pressure sensor, a flow sensor, and a displacement sensor; wherein: The negative pressure sensor is disposed in the negative pressure pipeline or the negative pressure chamber (120). The jet pressure sensor is disposed in the drug liquid pipeline or the jet component (130). The flow sensor is installed in the drug solution pipeline; The displacement sensor is disposed on the end body (110).

6. The negative pressure synergistic jet transdermal delivery device according to claim 2, characterized in that, The sealing structure (140) is fixed to the mating end face of the end body (110), and the mating end face of the end body (110) is configured to contact the target area; At least a portion of the sealing structure (140) protrudes from the mating end face of the end body (110) to form a sealing contact with target areas of different curvatures.

7. The negative pressure synergistic jet transdermal delivery device according to claim 6, characterized in that, The execution end (100) also includes a sterile contact element, which includes an annular sealing fitting part and a sterile nozzle channel part. The annular sealing fitting part is connected to the sealing structure (140), the sterile nozzle channel part is connected to the jet element (130), and the sterile nozzle channel part is pluggably connected to the drug liquid pipeline.

8. The negative pressure synergistic jet transdermal delivery device according to claim 1, characterized in that, The execution end (100) further includes an adjustment mechanism (150), which is disposed between the jetting element (130) and the end body (110). The adjustment mechanism (150) is used to adjust the position of the jetting port (131) of the jetting element (130) inside the negative pressure chamber (120); and / or, The jet nozzle (131) of the jet element (130) includes a plurality of micro-nozzles, which are arranged in at least one of a ring array or a rectangular array.

9. The negative pressure synergistic jet transdermal delivery device according to claim 1, characterized in that, The execution end (100) also includes an anti-backflow structure (160), which is disposed at the inflow end of the jet member (130).

10. The negative pressure synergistic jet transdermal delivery device according to claim 1, characterized in that, The negative pressure value within the negative pressure chamber (120) is reduced by 5 kPa to 80 kPa relative to atmospheric pressure; and / or, The pulse width output by the jet element (130) is from 1 ms to 1000 ms; and / or, The jetting frequency of the pulsed jet output by the jetting element (130) is from 0.05 Hz to 50 Hz; and / or, The pressure source outputs a pressure value of 0.05 MPa to 30 MPa; and / or, The negative pressure source is a miniature vacuum pump, a negative pressure pump, a syringe-type negative pressure generator, or a Venturi negative pressure generator; and / or, The pressure source is a pneumatic drive assembly, a mechanical spring drive assembly, a piezoelectric drive assembly, an electromagnetic drive assembly, a diaphragm pump drive assembly, or a plunger pump drive assembly.

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