A breath-synchronized micro-dosing device and method for nebulized inhalation of infants and young children

Abstract

This invention discloses a respiratory-synchronized micro-dosing drug delivery device and method for nebulized inhalation in infants and young children, relating to the biomedical field. The device includes a nebulizing mask, a three-way airflow tube, a differential pressure sensor, a microprocessor, and a micro-dosing drug delivery component. The differential pressure sensor collects the air pressure signal within the three-way airflow tube. The microprocessor calculates the slope of the air pressure change in real time. When the slope meets preset conditions, it determines the moment of inhalation initiation and triggers the micro-dosing drug delivery component to release a fixed volume of drug solution in a single nebulization into the three-way airflow tube. Simultaneously, the effective inhalation window ends and the lockout is released by the slope recovery, achieving single-dose drug delivery within the same cycle. This invention utilizes the slope of the air pressure change as a time-domain criterion for inhalation initiation, locking the drug delivery action at the initial stage of inhalation in infants and young children, achieving micro-level precision in drug delivery, significantly improving the drug deposition rate in the lungs, and is suitable for infants and young children with fast respiratory rates and short inhalation times.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more particularly to medical nebulized drug delivery devices, specifically a respiratory-synchronized micro-dosage delivery device and method for nebulized inhalation in infants and young children. Background Technology

[0002] Nebulized inhalation therapy is a widely used method of drug delivery in the treatment of respiratory diseases. It transforms liquid medication into aerosol particles, allowing the drug to directly reach the airways and affected areas of the lungs via the inhaled airflow. It offers advantages such as rapid onset of action, low dosage, and minimal systemic side effects. In pediatric clinical practice, nebulized inhalation is an important means of treating infantile asthma, bronchiolitis, pneumonia, and other diseases.

[0003] The respiratory physiology of infants and young children differs significantly from that of adults. The respiratory rate of normal infants and young children can reach 40-60 breaths per minute, and the duration of the inspiratory phase is extremely short, usually only 0.3-0.5 seconds. Moreover, their respiratory rhythm is irregular and is often accompanied by involuntary behaviors such as crying and wriggling. As a result, their breathing pattern is characterized by high frequency, shallow and rapid, and irregularity. Therefore, their physiological characteristics place higher demands on the response speed and drug delivery accuracy of nebulized drug delivery devices than on adult devices.

[0004] Currently, most nebulizers for infants and young children used in clinical practice employ continuous spray mode, which means that drug aerosols are continuously generated during treatment without distinguishing between the inspiratory and expiratory phases of the child's breathing. Because the inspiratory phase accounts for a relatively small proportion of the respiratory cycle in infants and young children, a large amount of the drug mist generated by continuous spray escapes into the surrounding environment through the mask's exhaust port during the expiratory phase, resulting in extremely low actual drug utilization and a typically low actual lung deposition rate. Most of the drug is wasted in the environment or deposited on the mask and tubing walls.

[0005] Besides the problem of drug waste, most traditional nebulizers rely solely on preset timers or flow controllers to control the total dosage throughout the treatment process, lacking the ability to respond in real time to individual respiratory events. In actual use, their open-loop control method cannot distinguish between the onset of the child's inhalation and exhalation, nor can it detect changes in the intensity of a single breath. This can lead to multiple doses being administered within the same respiratory cycle, or the continuous release of drug mist after the inspiratory phase has ended. This problem is particularly prominent for infants and young children with fast respiratory rates and short inspiratory times. As a result, the effective dosage of a single breath is uncontrollable, and overdosing and underdosing alternate in adjacent respiratory cycles, affecting the predictability of therapeutic effects and increasing the risk of adverse drug reactions. Summary of the Invention

[0006] This invention overcomes the shortcomings of the prior art and provides a respiratory-synchronized micro-dose drug delivery device and method for infant nebulized inhalation. By real-time monitoring of the slope of the air pressure change in the three-way air delivery tube, the falling edge of the slope is used to capture the moment of inhalation initiation, and the rising inflection point of the slope is used to define the termination time of the effective inhalation work window. The release action of a single fixed volume of drug solution is locked at the beginning of the infant's inhalation, which can achieve precise synchronization between the drug delivery time and the peak of the inhalation airflow dynamics, thereby effectively improving the drug deposition rate in the lungs and reducing the variability of drug dosage between breaths.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: Firstly, the present invention provides a respiratory-synchronized micro-dosing drug delivery device for nebulized inhalation in infants and young children, comprising:

[0008] A nebulizer mask is used to cover the child's mouth and nose to create a breathing cavity;

[0009] The air guide tee has a main air inlet, a main air outlet and a side branch port. The main air inlet is used to connect to an external air supply source, and the main air outlet is connected to the air inlet end of the atomizing mask.

[0010] A differential pressure sensor is installed at the side branch port to collect the air pressure signal inside the air guide tee.

[0011] The microprocessor is connected to the differential pressure sensor and is used to output a control signal based on the air pressure signal.

[0012] A micro-dosing delivery component is connected to the microprocessor for control.

[0013] The microprocessor determines the moment of inhalation initiation and the end time of the effective inhalation work window based on the slope of the air pressure change of the air pressure signal. At the moment of inhalation initiation, it synchronously outputs a drive pulse to the micro-dose drug delivery component to release the drug liquid into the air delivery three-way tube in a single fixed volume manner and atomize the drug liquid.

[0014] In a preferred embodiment of the present invention, the pressure sensing end of the differential pressure sensor is sealed and connected to the side branch port of the air guide tee; the signal output end of the differential pressure sensor is electrically connected to the analog-to-digital conversion pin of the microprocessor through a signal amplifier, for amplifying the collected air pressure signal and transmitting it to the microprocessor.

[0015] In a preferred embodiment of the present invention, the microprocessor has a built-in timer and a comparator. The timer is used to set the sampling time interval, and the comparator is used to compare the real-time calculated slope of the air pressure change with a preset threshold to determine the moment of inhalation initiation and the end time of the effective inhalation work window.

[0016] In a preferred embodiment of the present invention, the micro-dose delivery component includes a micro plunger metering pump and a piezoelectric nebulizer.

[0017] The micro plunger metering pump has a drive motor, an inlet and an outlet. The micro plunger metering pump is connected to the microprocessor for control and is used to squeeze out a fixed volume of liquid medicine with a fixed stroke after receiving the drive pulse from the microprocessor.

[0018] The piezoelectric atomizing plate is disposed on the inner wall of the main air outlet of the air guide tee, and is used to generate high-frequency vibration after receiving the oscillation drive signal of the microprocessor to atomize the liquid medicine.

[0019] In a preferred embodiment of the present invention, a pulse drive link is formed between the microprocessor and the drive motor of the micro plunger metering pump, and the microprocessor sends a drive pulse with a fixed pulse width to the drive motor when it determines the moment of inhalation start.

[0020] The microprocessor and the piezoelectric atomizing plate form an oscillation drive link, and the microprocessor sends signals to the drive motor and the piezoelectric atomizing plate at the same time.

[0021] In a preferred embodiment of the present invention, the microprocessor has a built-in latch register, which is set after the micro plunger metering pump and the piezoelectric atomizing plate are triggered to shield repeated trigger signals within the same inhalation cycle, and is reset to zero at the end of the effective inhalation work window.

[0022] In a preferred embodiment of the present invention, the invention further includes a drug reservoir and a liquid supply capillary; the drug reservoir is connected to the inlet of the micro plunger metering pump via the liquid supply capillary; the outlet of the micro plunger metering pump is connected to the back liquid chamber of the piezoelectric atomizing plate via another section of the liquid supply capillary.

[0023] In a preferred embodiment of the present invention, a one-way exhaust valve is further included. The one-way exhaust valve is disposed at the exhaust port on the side wall of the atomizing mask, and the conduction direction of the one-way exhaust valve is configured to allow only the gas inside the atomizing mask to be discharged to the outside atmosphere in one direction.

[0024] Secondly, the present invention provides a method for respiratory-synchronized micro-dose administration of medication via nebulization for infants and young children, implemented using the medication administration device described in any one of the above-mentioned methods, the medication administration method comprising the following steps:

[0025] S1. The differential pressure sensor collects the air pressure signal in the air guide three-way tube in real time at a preset sampling time interval. The microprocessor calculates the slope of the air pressure change over time based on the collected air pressure signal. When the slope of the change meets the preset inhalation start judgment condition, the current moment is determined to be the effective start moment of the inhalation phase.

[0026] S2. After the inspiratory phase is determined to start, the microprocessor continuously calculates the change slope. When the change slope meets the preset inspiratory end determination condition, the effective work window of this inspiratory phase is determined to end.

[0027] S3. At the instant the inhalation phase is determined to start, the microprocessor simultaneously sends a drive signal to the micro-dose delivery component. The micro-dose delivery component responds to the drive signal by squeezing out the liquid drug in a single fixed volume and atomizing and releasing the liquid drug into the air-conducting three-way tube.

[0028] S4. After step S3 is completed, the microprocessor initiates the same-cycle anti-repetition interlock, blocking the repeated triggering signal within the same inspiratory cycle until the effective work window of the current inspiratory phase ends, at which point the interlock is released, allowing the execution of steps S1-S3 to be repeated when the next inspiratory phase is started.

[0029] In a preferred embodiment of the present invention, in step S4, the microprocessor implements the anti-repeating locking through a built-in latch register:

[0030] After step S3 is completed, the latch register will set the latch flag bit;

[0031] During the period when the locking flag is in the specified position, the microprocessor blocks all repetitive triggering signals to the micro-dosing delivery component;

[0032] When the effective working window for inhalation is determined to be over, the microprocessor will clear and reset the latch flag.

[0033] This invention addresses the shortcomings of the prior art and has the following beneficial effects:

[0034] (1) This invention provides a respiratory-synchronized micro-dosing drug delivery device and method for infant nebulized inhalation. The microprocessor calculates the slope of the air pressure change in the three-way air delivery tube in real time with a fixed sampling period, and uses the slope falling at a preset threshold as the criterion for inhalation initiation. The trigger judgment is completed before the stable airflow is established, and a drive signal is sent to the micro plunger metering pump and the piezoelectric nebulizer. Since the slope reflects the trend speed of the air pressure change rather than the result amplitude of the change, this judgment mechanism can capture the initial movement of the diaphragm moving down before the air pressure amplitude has dropped significantly, so that the drug delivery command is issued earlier than the existing threshold triggering method. Compared with the existing threshold triggering technology, which must wait for the airflow to be established to a identifiable level before it can act, and has an inherent time delay, this invention moves the drug delivery action forward to the initial stage of inhalation, so that the peak value of the nebulized particles coincides with the peak value of the inhaled airflow on the time axis, and the drug can penetrate deep into the lower respiratory tract with the airflow.

[0035] (2) The microprocessor of this invention further uses the slope rising back to a preset threshold as the termination condition for the effective inhalation work window, and triggers the latch register to reset to zero when the condition is met. Since the inflection point where the slope rises from a negative value to a positive value precisely corresponds to the turning point where the inhalation airflow changes from acceleration to deceleration, this determination method is much earlier on the time axis than when the amplitude drops to a certain percentage value. In contrast, existing amplitude-type or duration-type criteria cannot identify this turning point and can only determine the end after the airflow amplitude has significantly decreased, resulting in the subsequent release of drug mist depositing in the oropharynx due to insufficient kinetic energy during the airflow deceleration phase. This invention locks the effective drug delivery window in the airflow acceleration phase and the early deceleration phase, which can exclude the ineffective later stage of the deceleration phase, thereby concentrating the release of a fixed volume of drug liquid within the time window with the highest delivery efficiency in this inhalation cycle.

[0036] (3) In this invention, the microprocessor uses the slope of the pressure change only as a logic switch. The actual value of the slope does not participate in the modulation of the drug dosage. The micro plunger metering pump outputs a fixed volume of drug solution per breath with a fixed stroke, thereby severing the regulatory coupling between respiratory intensity and drug dosage. The drug dosage for each breath is determined only by the mechanical stroke of the micro plunger metering pump. Compared with existing proportional regulation technologies where the drug dosage fluctuates with the inspiratory force and duration, resulting in significant dose variation between breaths, in this invention, regardless of the depth and strength of the child's next breath, the single drug dosage volume remains constant, thereby improving the controllability and consistency of drug dosage and allowing for accurate prediction of clinical drug dosage.

[0037] (4) The microprocessor of this invention has a built-in latch register. By setting the latch flag after each drug administration trigger, it blocks all repeated trigger signals to the micro-dose drug delivery component within the same inspiratory cycle until the effective work window of the current inspiratory cycle ends, at which point the register is reset. This timing latch mechanism can forcibly limit each inspiratory cycle to only one drug administration action from the control logic level, thereby avoiding multiple drug administrations within the same inspiratory phase. In contrast, existing devices may be triggered multiple times within the inspiratory phase, resulting in uncontrollable single-breath drug administration. This invention precisely constrains the single-breath drug administration to a fixed volume through latch logic, thereby avoiding the alternation of under-dosing and over-dosing in the same patient.

[0038] (5) This invention, by setting a one-way exhaust valve at the exhaust port on the side wall of the atomizing mask, allows only the gas inside the mask to be discharged to the outside atmosphere in one direction. The airflow during the exhalation phase can be discharged directly through the exhaust port without flowing through the air-conducting three-way tube, so that the sensitive end of the differential pressure sensor is not disturbed by the exhaled airflow during the exhalation phase, and purely reflects the real negative pressure change generated by the expansion of the chest cavity during the inhalation phase, which can improve the signal-to-noise ratio of the sensor's acquired signal. Compared with the existing slope algorithm applications, which usually rely on software filtering to suppress noise, but the filtering stage introduces phase delay, this invention relies on this physical isolation so that the slope determination can directly use the original differential signal without software smoothing filtering, ensuring the response speed while avoiding false triggering caused by noise interference. Attached Figure Description

[0039] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0040] Figure 1 This is a schematic diagram of the overall structure of the respiratory-synchronized micro-dosing drug delivery device of the present invention;

[0041] Figure 2 This is a partial half-section diagram of the connection between the air-conducting three-way tube and the micro-dose drug delivery component of the present invention;

[0042] Figure 3 This is a schematic flowchart of the respiratory-synchronized micro-dose drug delivery method of the present invention;

[0043] Figure 4 This is a time-series diagram illustrating the determination of air pressure slope and drug administration according to the present invention;

[0044] In the diagram: 1. Atomizing mask; 2. Air duct 3; 21. Main air inlet; 22. Main air outlet; 23. Side branch port; 3. Differential pressure sensor; 4. Signal amplifier; 5. Microprocessor; 6. Miniature plunger metering pump; 61. Drive motor; 62. Liquid inlet; 63. Liquid outlet; 7. Drug reservoir; 8. Liquid supply capillary; 9. Piezoelectric atomizing plate; 91. Back side liquid chamber; 92. Atomizing surface; 10. One-way exhaust valve; 11. Side wall exhaust port. Detailed Implementation

[0045] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0046] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein. Therefore, the scope of protection of the invention is not limited to the specific embodiments disclosed below.

[0047] In the description of this application, it should be understood that the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined with "first," "second," etc., may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0048] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "connected," "linked," and "set up" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; 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; and they can refer to the internal connection of two components. Those skilled in the art will understand the specific meaning of the above terms in this application based on the specific circumstances.

[0049] Application Overview:

[0050] To address the problems associated with traditional continuous nebulization and timed / flow-controlled methods, some existing technologies attempt to combine respiratory detection with nebulization triggering to synchronize drug delivery with respiratory rhythm. For example, Chinese invention patent CN121466432A discloses a lung-targeted drug nebulization delivery device with respiratory triggering, which uses two differential pressure airflow sensors to monitor the "positive pressure difference" in the respiratory tract to determine the start of inspiration.

[0051] This device is essentially a threshold-triggered type, which is inherently unsuitable for infants and young children. Because infants and young children have weak inspiratory muscles and a gentle inspiratory airflow, there is a significant time delay between the onset of diaphragmatic movement and the generation of a stable and detectable positive pressure difference at the mask end. This approach inherently requires the airflow to be established and reach a certain intensity before triggering, resulting in the nebulization initiation time always lagging behind the actual inspiratory airflow initiation time. The peak drug concentration produced by nebulization lags behind the peak inspiratory airflow. According to aerosol dynamics principles, a large number of drug particles cannot obtain sufficient axial kinetic energy and impact and deposit in the oropharynx and glottis region, making it difficult for them to enter the lower respiratory tract with the airflow.

[0052] Building upon this, more advanced technologies have proposed a drug delivery strategy that dynamically adjusts the length and proportion of drug delivery pulses based on respiratory characteristics. The basic logic is as follows: the patient's respiratory signals are collected in real time by flow or pressure sensors. Based on the peak flow rate or duration of the inspiratory airflow, a dynamically variable driving pulse width or duty cycle is calculated using proportional-integral-differential or similar algorithms. That is, a longer pulse is output to release more drug when the inspiratory force is strong and the inspiratory time is long, and a shorter pulse is output to release less drug when the inspiratory force is weak and the inspiratory time is short, so as to achieve proportional tracking between drug dosage and respiratory work intensity.

[0053] The applicant discovered that the core logic of this strategy is based on a sequential control framework of "measure first, calculate later, then output." The sensor must first acquire a sufficiently long inspiratory signal sample before the processor can extract the amplitude and calculate the duration of that signal, thereby calculating the corresponding pulse length or proportional coefficient. This means that the technology can only issue a drug delivery command after the inspiratory airflow has been established and stabilized. Essentially, it is a delayed response to an already occurring respiratory event, rather than a prediction of an impending one. For infants and young children with a total inspiratory phase duration of only 0.3-0.5 seconds, signal acquisition and calculation delays often occupy a large portion of the total inspiratory phase. By the time the driving pulse is finally output, the inspiratory airflow has already entered a plateau phase or even begun to decay. The peak value of the aerosol generated by nebulization lags significantly behind the peak value of the inspiratory airflow, preventing the nebulized particles from effectively penetrating the alveolar region and thus limiting further improvement in treatment efficacy.

[0054] In response to the above problems, such as Figure 1 and Figure 2 As shown, this invention proposes a respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation, comprising:

[0055] A nebulizer mask is used to cover the child's mouth and nose to create a breathing cavity;

[0056] The air guide tee has a main air inlet, a main air outlet and a side branch port. The main air inlet is used to connect to an external air supply source, and the main air outlet is connected to the air inlet end of the atomizing mask.

[0057] A differential pressure sensor is installed at the side branch port to collect the air pressure signal inside the air guide tee.

[0058] The microprocessor is connected to the differential pressure sensor and is used to output a control signal based on the air pressure signal.

[0059] A micro-dosing delivery component is connected to the microprocessor for control.

[0060] The microprocessor determines the moment of inhalation initiation and the end time of the effective inhalation work window based on the slope of the air pressure change of the air pressure signal. At the moment of inhalation initiation, it synchronously outputs a drive pulse to the micro-dose drug delivery component to release the drug liquid into the air delivery three-way tube in a single fixed volume manner and atomize the drug liquid.

[0061] The core concept of this invention is that the microprocessor 5 does not rely on the absolute value of air pressure or the integral result of the respiratory event that has occurred. Instead, it performs differential processing on the air pressure signal collected by the differential pressure sensor 3 in the time domain, calculates the slope of air pressure change in real time, and accurately defines the effective working window with the highest delivery efficiency in one inhalation cycle based on the falling edge and rising edge of the slope. Then, at the moment the window starts, it synchronously outputs a drive pulse with a fixed pulse width to the micro-dose drug delivery component, and releases and atomizes the drug liquid into the guide air three-way tube 2 in a single fixed volume manner.

[0062] The basic principle is that the slope, as the derivative of air pressure with respect to time, reflects the trend and speed of air pressure change, not its absolute value. By shifting the processing method of pressure signals from the traditional amplitude domain to the time domain, this invention can utilize the negative abrupt change in slope to capture the initial downward movement of the diaphragm before the air pressure amplitude has significantly decreased, achieving proactive prediction rather than delayed response. Simultaneously, the inflection point of the slope's rebound precisely corresponds to the turning point where the inspiratory airflow transitions from acceleration to deceleration, thereby locking the drug delivery window onto the most favorable ascending phase and early deceleration phase for aerosol delivery. This solves the drug delivery lag problem caused by the sequential control framework of measurement, calculation, and output in existing technologies, as well as the uncontrollable dosage problem caused by respiratory variability.

[0063] The following will describe in detail, with reference to the accompanying drawings and embodiments, the specific implementation of the above core concept, the structure of each component, the connection relationship and their collaborative working process.

[0064] Example 1:

[0065] This embodiment provides a respiratory-synchronized micro-dosing drug delivery device for nebulized inhalation in infants and young children.

[0066] Specifically, such as Figure 1As shown, the nebulizer mask 1 is the interface that comes into direct contact with the child. Its edges are made of soft silicone to ensure a close fit to the child's face during use, covering both the mouth and nose to form a closed breathing cavity. The nebulizer mask 1 can be secured by wrapping it around the back of the child's head using a standard headband attachment to ensure it doesn't easily fall off when the infant cries or squirms. Side vents 11 are provided on the side wall of the nebulizer mask 1 to expel exhaled air.

[0067] In this embodiment, the air-guiding three-way pipe 2 serves as a flow channel for gas and drug mist, and it has a main air inlet 21, a main air outlet 22, and a side branch port 23. The main air inlet 21 is located at one end of the three-way pipe and is used to connect to the external oxygen supply pipeline to provide the system with a continuous or on-demand oxygen source. The main air outlet 22 is located at the other end and is directly connected to the air inlet of the atomizing mask 1, which is the final channel for the carrier gas and drug mist to enter the mask. The side branch port 23 is an independent pressure-sensing channel used to isolate and guide the internal air pressure to the sensor.

[0068] Furthermore, the pressure-sensing end of the differential pressure sensor 3 is fixed to the side branch port 23 via a sealed connector, ensuring that the static or dynamic pressure within the air duct 2 can be transmitted to the sensitive diaphragm of the differential pressure sensor 3 without loss. The signal output end of the differential pressure sensor 3 is electrically connected to the input end of the signal amplifier 4 via a wire, and the output end of the signal amplifier 4 is electrically connected to the analog-to-digital conversion pin of the microprocessor 5.

[0069] Understandably, the signal amplifier 4 is used to condition and amplify the weak differential voltage signal output by the differential pressure sensor 3 so that it meets the input range requirements of the analog-to-digital converter inside the microprocessor 5, thereby forming a barometric pressure signal acquisition link.

[0070] In this embodiment, the microprocessor 5 integrates or is configured via peripherals with a timer, an analog-to-digital converter, a comparator, a differential operation module, and a latch register. The microprocessor 5 is electrically connected to the drive motor 61 of the micro plunger metering pump 6 and the control terminal of the piezoelectric atomizing plate 9 via its pulse output pin, forming a pulse drive link and an oscillation drive link.

[0071] In this embodiment, as Figure 2 As shown, the micro-dose delivery assembly includes a micro plunger metering pump 6 and a piezoelectric atomizing plate 9. The micro plunger metering pump 6 has a drive motor 61, an inlet 62, and an outlet 63. The micro plunger metering pump 6 is connected to a microprocessor 5 for control and is used to squeeze out a fixed volume of liquid medicine with a fixed stroke after receiving the drive pulse from the microprocessor. The piezoelectric atomizing plate 9 is disposed on the inner wall of the main outlet 21 of the air guide tee 2 and is used to generate high-frequency vibration after receiving the oscillation drive signal from the microprocessor 5 to atomize the liquid medicine.

[0072] Furthermore, the drug reservoir 7 is a flexible container with variable volume, used to store liquid medicine; the outlet of the drug reservoir 7 is connected to the inlet 62 of the micro plunger metering pump 6 through a liquid supply capillary tube 8, and the outlet 63 of the micro plunger metering pump 6 is connected to the back liquid chamber 91 of the piezoelectric atomizing plate 9 through another liquid supply capillary tube 8.

[0073] Furthermore, the piezoelectric atomizing plate 9 is fixedly installed on the inner wall of the main air outlet 22 of the air guide tee 2, with its atomizing surface 92 facing the airflow direction of the main air outlet 22. Optionally, the piezoelectric atomizing plate 9 is a microporous piezoelectric atomizing plate, in which the liquid cavity 91 on the back side receives the liquid medicine, and then the liquid medicine is squeezed out from the micropores and atomized by high-frequency vibration.

[0074] like Figure 3 As shown, the core of the device of the present invention lies in its time-domain determination mechanism based on the slope of air pressure change, and the physical structure and logical interlock that work in conjunction with the mechanism.

[0075] The determination of the moment of inhalation initiation is as follows: During device operation, the timer of microprocessor 5 is set to a fixed sampling time interval, which is 10 ms in this embodiment; microprocessor 5 reads the air pressure value P amplified by signal amplifier 4 in real time through analog-to-digital conversion pin at this sampling period, and the differential operation module of microprocessor 5 then calculates the real-time slope K of the air pressure change with time, and the calculation formula is:

[0076] .

[0077] in, This represents the current air pressure value. The air pressure value is the value sampled 10 ms ago.

[0078] In a preferred embodiment, before performing slope calculation, the microprocessor 5 first processes the collected air pressure values. Normalization is performed to eliminate the influence of dimensions.

[0079] Specifically, normalization can be performed according to the formula In progress, among which and These are the maximum and minimum air pressure values ​​calibrated by the system, respectively.

[0080] Furthermore, microprocessor 5 uses the normalized air pressure value. The slope K is calculated. The first comparator built into the microprocessor 5 has a preset inspiratory initiation slope threshold K1. When the real-time calculated slope K first satisfies K ≤ K1, i.e., a negative abrupt change occurs in the slope, the first comparator outputs a trigger signal, and the microprocessor 5 determines that the current moment is the effective initiation instant of an inspiratory phase. This determination logic utilizes the characteristic that the slope reflects the changing trend, and can complete the determination 10-20 ms before the airflow stabilizes.

[0081] The determination of the end of the effective work window for inhalation is as follows: The second comparator built into the microprocessor 5 has a preset threshold K2 for the end of the inhalation peak slope, where K2 > K1. After determining the start of the inhalation phase, the microprocessor 5 does not stop calculating but continues to calculate the real-time changing slope K at 10 ms intervals. When the value of K rises back to K ≥ K2, the second comparator outputs a trigger signal, and the microprocessor 5 determines that the effective work window for this inhalation has ended. This rising inflection point is much earlier on the time axis than the moment when the air pressure amplitude drops to a certain preset percentage, which can accurately correspond to the turning point where the inhalation airflow changes from acceleration to deceleration.

[0082] The synchronous output and interlocking of micro-dose drug delivery are as follows: At the instant the first comparator determines that the inhalation phase has started, the microprocessor 5 performs two synchronous operations within the same operation cycle. The first operation is to send a first drive pulse with a fixed pulse width to the drive motor 61 of the micro plunger metering pump 6. After receiving the pulse, the drive motor 61 drives the plunger to advance with a fixed stroke, quantitatively drawing the drug solution in the drug reservoir 7 through the supply capillary 8 and squeezing out 2 μL to the back liquid chamber 91 of the piezoelectric atomizing plate 9. The second operation is to send a high-frequency oscillating electrical signal to the piezoelectric atomizing plate 9. After receiving the signal, the piezoelectric atomizing plate 9 generates high-frequency mechanical vibration, instantly atomizing the 2 μL of drug solution in the back liquid chamber 91 into aerosol particles, which enter the atomizing mask 1 with the inhalation airflow in the main outlet 22.

[0083] After the two operations are completed, the microprocessor 5 immediately sets the lockout flag in the built-in lockout register to 1. During the period when the lockout flag is 1, the microprocessor 5 blocks all repeated trigger signals to the micro plunger metering pump 6 and the piezoelectric nebulizer 9 until the second comparator determines that the effective work window of this inhalation has ended, i.e., K ≥ K2. Only then does the microprocessor 5 clear the lockout flag, allowing the above determination and drug delivery process to be re-executed when the next inhalation phase is started. This forces the drug delivery action to be performed only once per inhalation cycle at the control logic level.

[0084] In this embodiment, by setting a physical isolation and cooperation between the one-way exhaust valve 10 and the atomizing mask 1, the differential pressure sensor 3 and the microprocessor 5 can form a pressure signal acquisition link, providing pure and high signal-to-noise ratio raw data for slope calculation.

[0085] Specifically, such as Figure 1 As shown, the one-way exhaust valve 10 is located at the exhaust port 11 on the side wall of the atomizing mask 1. Its conduction direction is set to allow only the gas inside the atomizing mask 1 to be discharged to the outside atmosphere. During the exhalation phase, the air pressure inside the mask increases, and the exhaled hot and humid waste gas pushes open the valve plate of the one-way exhaust valve 10 and is directly discharged into the outside atmosphere through the exhaust port 11, without backflowing into the air guide tee 2. During the inhalation phase, a negative pressure is formed inside the mask, and the one-way exhaust valve 10 automatically and tightly closes under atmospheric pressure. The resulting expiratory isolation link ensures that the differential pressure sensor 3 is basically unaffected by airflow disturbance during the exhalation phase and purely reflects the real negative pressure change generated by chest expansion during the inhalation phase, effectively improving the signal-to-noise ratio. The slope determination can directly use the original differential signal without software smoothing filtering, thereby maintaining low response delay and avoiding noise-induced false triggering.

[0086] Understandably, the microprocessor 5 uses the slope only as a pure switching quantity rather than a modulation quantity. In this embodiment, regardless of whether the specific value of the slope is -0.8 or -1.2, as long as K ≤ K1, a fixed-stroke dosing is triggered. The single volume of the dosing is locked by the mechanical stroke of the micro plunger metering pump 6, which is decoupled from the actual intensity of each breath of the child, so that the dose variation coefficient (CV value) between breaths is significantly reduced compared with the technology that relies on amplitude ratio adjustment.

[0087] Example 2:

[0088] like Figure 3 As shown, this embodiment provides a method for respiratory-synchronized micro-dose drug delivery for nebulized inhalation in infants and young children, including the following steps:

[0089] S1. Real-time monitoring and determination of the inspiratory initiation slope: The microprocessor 5, through its analog-to-digital conversion pin, acquires the air pressure signal from the differential pressure sensor 3, amplified by the signal amplifier 4, in real time with a sampling period of ≤10 ms. The differential operation module built into the microprocessor 5 then calculates the air pressure change slope K at the current moment. The first comparator built into the microprocessor 5 presets the inspiratory initiation slope threshold K1. When the real-time change slope K first satisfies K ≤ K1, the first comparator outputs a trigger signal, and the microprocessor 5 determines that the current moment is an effective initiation moment of the inspiratory phase.

[0090] S2. Determination of the end of the effective work window of inhalation: After the inhalation phase is determined to start, the microprocessor 5 does not stop calculating, but enters the continuous monitoring phase. The microprocessor 5 continuously calculates the real-time change slope K at a period of 10 ms. The second comparator built into the microprocessor 5 presets the inhalation peak end slope threshold K2, where K2> K1. When the value of K rises back to K ≥ K2, the second comparator outputs a trigger signal, and the microprocessor 5 determines that the effective work window of this inhalation has ended.

[0091] S3. Synchronous output of micro-dose administration pulse: At the instant the inspiratory phase is started, the microprocessor 5 simultaneously sends a drive signal to the drive motor 61 of the micro plunger metering pump 6 and the piezoelectric atomizing plate 9 within the same calculation cycle. Specifically, a first drive pulse with a fixed pulse width is sent to the drive motor 61, causing it to drive the plunger forward with a fixed stroke, quantitatively squeezing 2 μL of the drug solution in the drug reservoir 7 into the back liquid chamber 91 of the piezoelectric atomizing plate 9; at the same time, a high-frequency oscillating electrical signal is sent to the piezoelectric atomizing plate 9, causing it to instantaneously atomize the 2 μL of drug solution in the back liquid chamber 91, ensuring the consistency of the timing of drug extrusion and atomization, and avoiding the retention of drug solution in the back liquid chamber 91.

[0092] S4. Same-cycle anti-repeated dosing lockout: At the same moment after the completion of step S3, i.e. after the drive pulse is issued, the microprocessor 5 immediately sets the lockout flag in its built-in lockout register to 1. During the period when the lockout flag is 1, the microprocessor 5 blocks all repeated triggering signals to the micro plunger metering pump 6 and the piezoelectric nebulizer 9. No matter how the slope K fluctuates afterward, the microprocessor 5 will only clear the lockout flag when the effective work window of this inhalation is determined to be over in step S2, i.e., when the condition K ≥ K2 is met, so that the system is reset and steps S1 to S3 are re-executed when the next inhalation phase is started.

[0093] Figure 4 The above timing logic is demonstrated as follows: at time t1, K ≤ K1, drug administration is triggered and the lockout is set; during the entire effective inhalation window from t1 to t2, although the slope may fluctuate, the lockout flag is valid, blocking all repeated triggers; at time t2, K ≥ K2, the effective window ends, the lockout flag is cleared, and the system is ready to respond to the next inhalation.

[0094] To further verify the technical effects of the present invention, a comparative experiment was conducted on a test platform simulating infant breathing patterns.

[0095] The experiment was divided into three groups: Group A was the device and method of the present invention, Group B was the traditional continuous spray nebulizer (model ZS-17-A medical compressor nebulizer), and Group C was the dynamic adjustment nebulizer using a proportional following strategy.

[0096] The test used a YZ1234-I metrology-adjustable iron lung to simulate infant breathing. The respiratory rate was set at 50 breaths / min, the inspiratory phase time at 0.4 s, and the tidal volume at 50 mL. High-performance liquid chromatography (HPLC) was used to quantitatively analyze the mass of drug deposited in the lower respiratory tract (terminal trachea and below) of the simulated lung, and the lung deposition rate was calculated based on the delivered dose. Simultaneously, the single-dose administration within 5 minutes of continuous operation for each group was recorded, and the coefficient of variation (CV) was calculated. The experimental results are summarized in Table 1.

[0097] Test metrics Group A Group B Group C Lung deposition rate (%) 23.5 4.2 11.8 Drug escape rate (%) 12.8 74.5 45.6 Coefficient of variation (CV%) of a single dose 2.8 / ±52.3 Response latency (ms) 8 / 75

[0098] As shown in Table 1, the lung deposition rate of Group A of the device and method of the present invention reached 23.5%, which is significantly higher than that of Group B (continuous spray mode, 4.2%) and Group C (proportion-following strategy, 11.8%). Correspondingly, the drug escape rate was reduced to 12.8%, far lower than that of Group B (74.5%) and Group C (45.6%). The results indicate that the present invention, by precisely locking the drug delivery action at the initial stage of inhalation, makes the peak value of atomized particles coincide with the peak value of inspiratory airflow on the time axis, which can effectively avoid drug escape in the expiratory phase and inertial impaction deposition in the oropharynx.

[0099] Furthermore, the CV value for a single dose of this invention is only 2.8%, while group B cannot be defined due to continuous dosing, and group C has a CV as high as 52.3%. This verifies that the strategy of this invention, which uses the slope as a pure switching quantity and locks the dosing volume using the fixed stroke of the micro plunger metering pump 6, can break the coupling between the dosage and respiratory variability, thereby achieving highly controllable and consistent micro-dosing. In contrast, techniques that rely on amplitude proportional adjustment result in drastic fluctuations in dosage with the depth and strength of the child's breathing, leading to the clinical risk of both underdosing and overdosing.

[0100] Furthermore, the response delay of this invention is controlled to within 10 ms. Group B is not applicable due to continuous dosing and is far superior to the 75 ms delay of Group C. For infants and young children with an inspiratory phase of only 0.4 s, the 75 ms delay in Group C accounts for nearly 20% of the total inspiratory phase duration, meaning that its drug release peak must lag behind the airflow peak. The 8 ms response delay of this invention is essentially negative delay compensation, which can ensure that the dosing command is issued earlier than the establishment of a stable airflow, thereby achieving advanced prediction.

[0101] The above description is based on the preferred embodiments of the present invention. It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered exemplary and non-limiting in all respects. The scope of the invention is defined by the appended claims rather than the foregoing description, and all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0102] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A respiratory-synchronized micro-dosing drug delivery device for nebulized inhalation in infants and young children, characterized in that, include: A nebulizer mask is used to cover the child's mouth and nose to create a breathing cavity; The air guide tee has a main air inlet, a main air outlet and a side branch port. The main air inlet is used to connect to an external air supply source, and the main air outlet is connected to the air inlet end of the atomizing mask. A differential pressure sensor is installed at the side branch port to collect the air pressure signal inside the air guide tee. The microprocessor is connected to the differential pressure sensor and is used to output a control signal based on the air pressure signal. A micro-dosing delivery component is connected to the microprocessor for control. The microprocessor determines the moment of inhalation initiation and the end time of the effective inhalation work window based on the slope of the air pressure change of the air pressure signal. At the moment of inhalation initiation, it synchronously outputs a drive pulse to the micro-dose drug delivery component to release the drug liquid into the air delivery three-way tube in a single fixed volume manner and atomize the drug liquid.

2. The respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 1, characterized in that, The pressure sensing end of the differential pressure sensor is sealed and connected to the side branch port of the air duct tee; the signal output end of the differential pressure sensor is electrically connected to the analog-to-digital conversion pin of the microprocessor through a signal amplifier, which is used to amplify the collected air pressure signal and transmit it to the microprocessor.

3. The respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 1, characterized in that, The microprocessor has a built-in timer and comparator. The timer is used to set the sampling time interval, and the comparator is used to compare the real-time calculated slope of the air pressure change with a preset threshold to determine the moment of inhalation initiation and the end time of the effective inhalation work window.

4. The respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 1, characterized in that, The micro-dose delivery component includes a micro plunger metering pump and a piezoelectric atomizing plate; The micro plunger metering pump has a drive motor, an inlet and an outlet. The micro plunger metering pump is connected to the microprocessor for control and is used to squeeze out a fixed volume of liquid medicine with a fixed stroke after receiving the drive pulse from the microprocessor. The piezoelectric atomizing plate is disposed on the inner wall of the main air outlet of the air guide tee, and is used to generate high-frequency vibration after receiving the oscillation drive signal of the microprocessor to atomize the liquid medicine.

5. A respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 4, characterized in that, The microprocessor and the drive motor of the micro plunger metering pump form a pulse drive link. When the microprocessor determines the moment of inhalation start, it sends a drive pulse with a fixed pulse width to the drive motor. The microprocessor and the piezoelectric atomizing plate form an oscillation drive link, and the microprocessor sends signals to the drive motor and the piezoelectric atomizing plate at the same time.

6. A respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 4, characterized in that, The microprocessor has a built-in latch register, which is set after the micro plunger metering pump and the piezoelectric atomizing plate are triggered to shield repeated trigger signals within the same inhalation cycle, and is reset to zero at the end of the effective inhalation work window.

7. A respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 4, characterized in that, It also includes a drug reservoir and a liquid supply capillary; the drug reservoir is connected to the inlet of the micro plunger metering pump through the liquid supply capillary; the outlet of the micro plunger metering pump is connected to the back liquid chamber of the piezoelectric atomizing plate through another section of the liquid supply capillary.

8. A respiratory-synchronized micro-dosing drug delivery device for infant nebulization inhalation according to claim 1, characterized in that, It also includes a one-way exhaust valve, which is located at the exhaust port on the side wall of the atomizing mask. The one-way exhaust valve is configured to allow only the gas inside the atomizing mask to be discharged to the outside atmosphere in one direction.

9. A method for nebulized inhalation-synchronized micro-dose drug delivery for infants and young children, implemented using the drug delivery device according to any one of claims 1-8, characterized in that, The administration method includes the following steps: S1. The differential pressure sensor collects the air pressure signal in the air guide three-way tube in real time at a preset sampling time interval. The microprocessor calculates the slope of the air pressure change over time based on the collected air pressure signal. When the slope of the change meets the preset inhalation start judgment condition, the current moment is determined to be the effective start moment of the inhalation phase. S2. After the inspiratory phase is determined to start, the microprocessor continuously calculates the change slope. When the change slope meets the preset inspiratory end determination condition, the effective work window of this inspiratory phase is determined to end. S3. At the instant the inhalation phase is determined to start, the microprocessor simultaneously sends a drive signal to the micro-dose drug delivery component. The micro-dose drug delivery component responds to the drive signal by squeezing out the drug liquid in a single fixed volume and atomizing and releasing the drug liquid into the air-conducting three-way tube. S4. After step S3 is completed, the microprocessor initiates the same-cycle anti-repetition interlock, blocking the repeated triggering signal within the same inhalation cycle until the effective work window of the current inhalation ends, at which point the interlock is released, allowing the execution of steps S1-S3 to be repeated when the next inhalation phase is started.

10. A method for synchronized respiratory micro-dosage administration for nebulized inhalation in infants and young children according to claim 9, characterized in that, In step S4, the microprocessor implements the anti-repeating locking through a built-in latch register: After step S3 is completed, the latch register will set the latch flag bit; During the period when the locking flag is in the specified position, the microprocessor blocks all repetitive triggering signals to the micro-dosing delivery component; When the effective working window for inhalation is determined to be over, the microprocessor will clear and reset the latch flag.

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