A dual mode vapor phase monomolecular drug delivery device and system

Abstract

This invention discloses a dual-mode gas-phase single-molecule drug delivery device and system. The device includes a housing, an electronic control mechanism disposed inside the housing, and a drug delivery mechanism electrically connected to the electronic control mechanism. The housing includes an electronic control section for housing the electronic control mechanism and a drug delivery section for accommodating the drug delivery mechanism. The electronic control mechanism includes a power supply component electrically connected to the drug delivery mechanism and a control element for switching the power supply type of the power supply component. The power supply component passes through the drug delivery section and is used to ionize the drug solution within the drug delivery section to form an electrospray. The control element switches the drug delivery mode of the drug delivery mechanism by switching the positive and negative voltage states of the power supply component. This invention employs low-voltage driven bipolar electrospray technology to achieve nano- and micro-level atomization of the drug solution with low energy consumption and a small device size, forming uniform positive / negative charged microdroplets. This lays the foundation for subsequent gas-phase molecule conversion and targeted delivery, improving atomization efficiency and device portability.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to a dual-mode gas-phase single-molecule drug delivery device and system. Background Technology

[0002] Lung delivery is an important drug delivery method that delivers drugs directly to the respiratory tract and alveoli via inhalation. It has advantages such as rapid onset of action, high bioavailability, avoidance of the first-pass effect of the liver, and fewer systemic side effects. It has important application value in the treatment of asthma, chronic obstructive pulmonary disease, pulmonary infections, lung cancer, and systemic diseases.

[0003] To achieve pulmonary drug delivery, the drug needs to be converted into an aerosol form suitable for inhalation. Currently, commonly used pulmonary drug delivery devices in clinical practice mainly include pressure metered-dose inhalers (pMDI), dry powder inhalers (DPI), and traditional nebulizers (such as jet nebulizers and ultrasonic nebulizers).

[0004] However, traditional nebulization technology produces aerosols with a wide particle size distribution and poor uniformity. Only a portion of drug particles can effectively deposit in the lungs, while a large amount of drug is deposited in the oropharynx or exhaled due to unsuitable particle size, resulting in low drug utilization. Furthermore, the energy required to generate inhalable aerosols is high, often resulting in bulky and inconvenient devices. In addition, traditional nebulization technology struggles to precisely guide and control the direction of nebulized drug particles or molecules. Drug distribution in the lungs largely depends on the recipient's breathing pattern and airflow dynamics, exhibiting significant individual differences. This makes it difficult to achieve specific high-concentration drug delivery to the lesion site, affecting treatment efficacy and potentially increasing local irritation. Moreover, existing pulmonary drug delivery devices cannot simultaneously address the clinical needs of targeted drug delivery to both the upper respiratory tract (larynx) and lower respiratory tract (lungs). For clinical scenarios such as laryngitis, vocal cord polyps, precancerous lesions of the larynx, and postoperative local drug delivery, high-concentration, precise deposition in superficial laryngeal tissues is required; while for diseases such as asthma, COPD, and lung infections, drugs need to avoid laryngeal adsorption as much as possible and efficiently enter the lungs. Existing devices cannot achieve the switching between the two drug delivery modes in a simple and controllable way. They often require different devices, which not only increases medical costs but also fails to meet the personalized drug delivery needs for home use. Summary of the Invention

[0005] Based on this, the purpose of the present invention is to provide a dual-mode gas-phase single-molecule drug delivery device and system, which aims to solve the problems of low atomization efficiency, inability to achieve the desired deposition efficiency, and poor delivery accuracy of current drug delivery devices.

[0006] To achieve the above objectives, the present invention proposes a dual-mode gas-phase single-molecule drug delivery device, which includes a housing, an electronic control mechanism disposed inside the housing, and a drug delivery mechanism electrically connected to the electronic control mechanism. The housing includes an electrical control section for mounting the electrical control mechanism and a drug delivery section for accommodating the drug delivery mechanism; The electrical control mechanism includes a power supply component electrically connected to the drug delivery mechanism, and a control element for switching the power supply type of the power supply component; The power supply component is inserted into the drug delivery section to ionize the drug solution in the drug delivery section to form an electrospray. The control unit switches the drug delivery mode of the drug delivery mechanism by switching the positive and negative voltage states of the power supply component.

[0007] According to one aspect of the above technical solution, the power supply assembly includes a power supply component disposed at one end of the power control section, a circuit board electrically connected to the power supply component, and an electrode rod electrically connected to the circuit board, wherein the end of the electrode rod away from the circuit board is inserted into the drug delivery section.

[0008] According to one aspect of the above technical solution, the input terminal of the circuit board is used to connect to the power supply component. The circuit board adopts a bipolar low-voltage drive structure with H-bridge inverter combined with symmetrical voltage multiplier rectification to convert the power supply component voltage into a preset low-voltage forward DC voltage and reverse DC voltage.

[0009] According to one aspect of the above technical solution, the control element is located at the end of the electrical control section away from the drug delivery section, and the control element is used to switch the polarity of the output voltage of the circuit board.

[0010] According to one aspect of the above technical solution, the drug delivery mechanism includes an external component connected to the drug delivery section and a drug delivery component disposed within the drug delivery section, with one end of the drug delivery component penetrating through the drug delivery section and entering the external component.

[0011] According to one aspect of the above technical solution, the sealing cover is movably connected to the external component and the drug delivery section, and the external pipe is inclinedly connected to the drug delivery section. The sealing cover and the drug delivery section enclose a drug storage chamber, and the drug delivery component passes through the external pipe.

[0012] According to one aspect of the above technical solution, the drug delivery assembly includes a drug delivery tube connecting the external tube and the drug storage chamber, and a conductive needle passing through the drug delivery tube, wherein one end of the conductive needle away from the drug delivery tube is connected to an electrode rod.

[0013] This invention also proposes a dual-mode gas-phase single-molecule drug delivery system, implemented based on the aforementioned dual-mode gas-phase single-molecule drug delivery device, the system comprising: The first adjustment module is used to inject the drug solution into the drug storage chamber and adjust the distance between the drug delivery device and the recipient's face; The second adjustment module is used to determine the target area for drug delivery, turn on the circuit board, use the control unit to switch the polarity of the output voltage of the circuit board, adjust the charge-carrying capacity of the conductive needle, and form nano- and micro-charged droplets of corresponding polarity at the tip of the drug delivery tube, which are then directly sprayed onto the target area for drug delivery.

[0014] According to one aspect of the above technical solution, in the step of using a control element to switch the output voltage polarity of the circuit board and adjust the electrical charge carried by the conductive needle: If the target area for drug delivery is the throat, the circuit board is set to output a positive DC voltage so that the conductive needle carries a positive charge; If the target area for drug delivery is the lungs, a reverse DC voltage is set to be output so that the conductive needle carries a negative charge.

[0015] According to one aspect of the above technical solution, the distance between the drug delivery device and the recipient's face is 1cm to 10cm; in the throat drug delivery mode, the adjustable distance is 1cm to 3cm; and in the lung drug delivery mode, the adjustable distance is 3cm to 10cm.

[0016] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention employs low-pressure driven bipolar electrospray technology to achieve nano- and micro-level atomization of the drug solution with low energy consumption and small device size, forming uniform positive / negative charged microdroplets, laying the foundation for subsequent gas phase molecular conversion and targeted delivery, and improving atomization efficiency and device portability. 2. This invention achieves dual-mode targeted drug delivery to the throat and lungs using a bipolar electrospray circuit and a polarity switching switch: When the electrode rod is positively charged, the generated positively charged drug droplets can generate an attraction-repulsion effect with the negatively charged human respiratory tract tissue, efficiently adsorbing onto the throat region to achieve precise local drug delivery for throat diseases; when the electrode rod is negatively charged, the generated negatively charged drug droplets can generate an repulsion-repulsion effect with the negatively charged human respiratory tract tissue, effectively avoiding adsorption in the throat and entering the lungs with the airflow, improving lung deposition efficiency. 3. The dual-mode drug delivery system of the present invention is fully controllable and does not require replacement of the device structure. It can be adapted to different drug delivery scenarios simply by switching electrically. It retains the advantages of the original device, such as portability, low power consumption and no external pollution, while greatly expanding the scope of clinical application. It can simultaneously meet the inhalation drug delivery needs of laryngeal and pulmonary diseases, and has both clinical value and market application prospects. 4. The entire system of the present invention has a compact structure, low power consumption, and does not require an external voltage source. It is suitable for personalized, home-based, or mobile medical scenarios, and provides an innovative and practical delivery tool for targeted treatment of respiratory diseases. 5. The method of the present invention achieves full controllability from liquid drug to gaseous molecules and then to targeted delivery. It has the advantages of no external pollution, high delivery efficiency and wide applicability. It has good application prospects in the treatment of respiratory diseases of the throat and lungs and in the pulmonary inhalation delivery of systemic drugs.

[0017] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the dual-mode gas-phase single-molecule drug delivery device in Embodiment 1 of the present invention; Figure 2 This is an internal cross-sectional view of the dual-mode gas-phase single-molecule drug delivery device in Embodiment 1 of the present invention; Figure 3 This is an enlarged schematic diagram of the drug delivery section in Embodiment 1 of the present invention; Figure 4 This is a schematic diagram of the structure of the gas-phase single-molecule drug delivery simulation experimental device according to Embodiment 2 of the present invention; Figure 5 This is a schematic diagram comparing the drug movement trajectory in the positive and negative electric modes of the present invention; Figure 6 This is a comparison chart of salbutamol deposition rates in the throat and lungs under the positive / negative charge modes of this invention. Figure 7 This is the UV absorption spectrum of salbutamol in Example 3 of the present invention; Figure 8 This is a comparative experimental result of the three nebulizers in Embodiment 3 of the present invention regarding their lung deposition efficiency. According to the diagram; Figure 9 A comparison diagram of droplet size distribution generated by the conventional manual jet atomizer, the conventional ultrasonic atomizer, and the device of the present invention. Figure 10 This is a comparison of the intensity of the characteristic ion peaks of salbutamol in the secondary distribution bottle sample after the three atomizing devices in Embodiment 5 of the present invention were collected by a glass double-stage impactor. Figure 11 This is a bar chart comparing the recovery of salbutamol in the primary and secondary distribution bottles of the three nebulizers in a simulated lung drug delivery experiment according to Embodiment 5 of the present invention.

[0019] Component symbol explanation in the attached diagram: 1. Drug storage chamber; 2. Electrode rod; 3. Conical microchannel; 4. Conductive needle; 5. Drug delivery tube; 6. Circuit board; 7. Power supply component; 8. Control component; 9. Housing; 10. Working status indicator light; 11. Primary distribution bottle; 12. Secondary distribution bottle; 13. Vacuum pump; 14. External pipe; 15. Sealing cap. Detailed Implementation

[0020] To make the objectives, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Several embodiments of the present invention are shown in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided so that the disclosure of the present invention will be more thorough and complete.

[0021] It should be noted that when an element is referred to as being "fixed to" another element, it can be directly on the other element or there may be an intervening element. When 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. The terms "vertical," "horizontal," "left," "right," "upper," "lower," and similar expressions used herein are for illustrative purposes only and are not intended to 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 limiting the invention.

[0022] In this invention, unless otherwise explicitly specified and limited, the terms "installation," "connection," "linking," and "fixing," etc., 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 communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention according to the specific circumstances. The term "and / or" as used herein includes any and all combinations of one or more of the related listed items.

[0023] Example 1 Please see Figures 1-3 The above is a schematic diagram of a dual-mode gas-phase single-molecule drug delivery device according to Embodiment 1. This dual-mode gas-phase single-molecule drug delivery device includes a housing 9, an electronic control mechanism disposed inside the housing, and a drug delivery mechanism electrically connected to the electronic control mechanism, wherein: The drug delivery device provided in this embodiment is integrated within a housing 9, which includes an electrical control section for mounting an electrical control mechanism and a drug delivery section for accommodating the drug delivery mechanism. Further, the electrical control mechanism includes a power supply component electrically connected to the drug delivery mechanism and a control element 8 for switching the power supply type of the power supply component. The power supply component passes through the drug delivery section to ionize the drug solution within the delivery section to form an electrospray. The control element switches the drug delivery mode of the drug delivery mechanism by switching the positive and negative voltage states of the power supply component.

[0024] Furthermore, the power supply assembly includes a power supply unit 7 located at one end of the electronic control section, a circuit board 6 electrically connected to the power supply unit 7, and an electrode rod 2 electrically connected to the circuit board 6, with one end of the electrode rod 2 away from the circuit board 6 extending into the drug delivery section. In this embodiment, the power supply unit 7 can be a rechargeable lithium polymer battery with a rated voltage of 3.7V and a capacity of 1500mAh, providing operating power for the entire device.

[0025] It should be noted that the circuit board 6 is equipped with a low-voltage bipolar electro-spray circuit, the input of which is connected to the power supply unit 7. The circuit board 6 adopts a bipolar low-voltage drive circuit design based on H-bridge inverter + symmetrical voltage doubler rectification, converting the 3.7V DC voltage provided by the battery into an adjustable bipolar voltage output of 0.5kV~5kV positive DC voltage or -0.5kV~-5kV reverse DC voltage. In order to control the output polarity of the circuit board 6 so that the electrode rod 2 has different voltage polarities, a control unit 8 is provided at the end of the electronic control section away from the drug delivery section. The control unit 8 has three positions (positive mode / off mode / negative mode), and the output polarity can be switched with one button. At the same time, a working status indicator light 10 can also be set on the housing 9. The working status indicator light 10 displays red to correspond to the positive electrical throat drug delivery mode and blue to correspond to the negative electrical lung drug delivery mode, so that the user can intuitively identify the current working status. In addition, the electrode rod 2 can be made of platinum-iridium alloy wire with a diameter of 0.5 mm. One end of the electrode rod is electrically connected to the voltage output terminal of the bipolar electrospray circuit, and the other end extends into the drug delivery section.

[0026] Furthermore, for administering medication to the recipient, the medication delivery mechanism includes an external component connected to the delivery section and a delivery component disposed within the delivery section, with one end of the delivery component penetrating through the delivery section and entering the external component. The external component is movably connected to a sealing cap 15 and the delivery section, and an external connecting pipe 14 is inclinedly connected to the delivery section. The sealing cap 15 and the delivery section enclose a drug storage chamber 1, and the delivery component passes through the external connecting pipe 14. In this embodiment, the drug storage chamber 1 can be made of medical-grade polycarbonate with a volume of 2 mL. The sealing cap 15 is detachably connected to the delivery section for easy drug injection and cleaning. A conical microchannel 3 is provided at the bottom of the drug storage chamber 1, with an inlet diameter of 300 μm, an outlet diameter of 50 μm, and a length of 15 mm. The end of the electrode rod 2 is led out through this conical microchannel 3.

[0027] Furthermore, the drug delivery assembly includes a drug delivery tube 5 connecting the outer tube 14 and the drug storage chamber 1, and a conductive needle 4 inserted inside the drug delivery tube 5. The end of the conductive needle 4 away from the drug delivery tube 5 is connected to the electrode rod 2. The tip diameter of the conductive needle 4 can be set to 20 μm for insertion into the inlet end of the drug delivery tube 5 to a depth of approximately 3 mm.

[0028] In practice, after injecting the drug solution into the drug storage chamber 1, the distance between the device and the recipient's face is adjusted, and the drug delivery mode is selected via a polarity switching switch. The bipolar electrospray circuit board 6 then operates, establishing an electric field of corresponding polarity between the conductive needle 4 and the external environment. The drug solution forms a stable electrospray at the tip of the delivery tube 5, generating corresponding polarity charged nano-droplets with a particle size primarily distributed in the 100-300 nm range, which are directly sprayed onto the target area. Throughout the entire operation, the device's operating current remains below 1.2 μA, and the power consumption is less than 5 mW.

[0029] Example 2 Please see Figure 4 This embodiment is based on the drug delivery device provided in Embodiment 1, and a lung nebulization drug delivery experimental device is built to conduct a simulation experiment.

[0030] To verify the efficacy of the bipolar switching system's dual-mode drug delivery (laryngeal / lung), a simulated human respiratory tract-lung deposition model was used to compare drug deposition distribution in positive and negative polarity modes, with drug movement trajectories referenced... Figure 5 , Figure 6 This is a comparison chart of salbutamol deposition rates in the throat and lungs under positive and negative charge modes.

[0031] The experimental setup in this embodiment uses an improved human respiratory tract simulation dual-stage impactor, in which the primary distribution bottle 11 simulates laryngeal deposition and the secondary distribution bottle 12 simulates lung deposition; the experimental drug is salbutamol, prepared with anhydrous ethanol at a concentration of 1 mg / mL, with a drug delivery volume of 2 mL and a delivery time of 30 seconds.

[0032] Experimental Group 1 (Positive Electrical Throat Administration Mode): The bipolar electrospray circuit outputs a positive DC voltage of 1.2kV, and the distance between the device and the impactor inlet is 2cm.

[0033] Experimental Group 2 (Negative Electronephrotic Drug Delivery Mode): The bipolar electrospray circuit outputs a reverse DC voltage of -1.2kV, and the distance between the device and the impactor inlet is 5cm.

[0034] The experimental results are as follows: Experimental group 1 (positive laryngeal mode): The recovery of salbutamol in primary distribution bottle 11 (laryngeal simulation) was 1.54 mg, accounting for 77.0% of the total dose; the recovery of salbutamol in secondary distribution bottle 12 (lung simulation) was 0.34 mg, accounting for 17.0% of the total dose; the total recovery rate was 94.0%.

[0035] Experimental group 2 (negatively charged lung mode): The recovery of salbutamol in primary distribution bottle 11 (laryngeal simulation) was 0.07 mg, accounting for 3.5% of the total dose; the recovery of salbutamol in secondary distribution bottle 12 (lung simulation) was 1.76 mg, accounting for 88.0% of the total dose; the total recovery rate was 91.5%.

[0036] The results of this embodiment demonstrate that the present invention can precisely control the drug deposition site by switching between positive and negative polarities: in positive polarity mode, based on the principle of attraction between opposite charges, the drug deposition rate in the larynx can reach 77%, meeting the local high-concentration drug delivery requirements for laryngeal diseases; in negative polarity mode, based on the principle of repulsion between like charges, the drug adsorption rate in the larynx is as low as 3.5%, while the lung deposition rate is increased to 88%, further optimizing the drug delivery effect. This invention significantly expands the clinical application scenarios of the device, realizing controllable targeted drug delivery with dual functionality.

[0037] Example 3 Based on the dual-mode gas-phase single-molecule drug delivery device provided in Example 1, a glass double-stage impactor, a vacuum pump 13, an ultraviolet-visible spectrophotometer and a matching data acquisition system were configured to build a lung nebulization drug delivery experimental device for simulation experiments. In this device, the primary distribution bottle 11 of the glass double-stage impactor simulates upper respiratory tract deposition, and the secondary distribution bottle 12 simulates lung deposition.

[0038] The experimental drug used was salbutamol, and an anhydrous ethanol was used to prepare an experimental drug solution with a concentration of 1 mg / mL.

[0039] In this embodiment, the experimental parameters were set as follows: the output voltage of the bipolar electrospray circuit was set to -1.2 kV (negative charge lung administration mode); the distance between the outlet end of the delivery tube 5 and the inlet of the dual-stage impactor was set to 5 cm; the inhalation flow rate of the vacuum pump 13 was set to 60 L / min; the single administration volume was 2 mL; and the administration duration was set to 30 seconds.

[0040] The lung-targeted gas-phase single-molecule drug delivery application in this embodiment includes the following steps: 7 mL of anhydrous ethanol was added to the primary distribution bottle 11 as the absorption solution, and 30 mL of anhydrous ethanol was added to the secondary distribution bottle 12 as the absorption solution. Inject 2 mL of salbutamol ethanol solution into storage chamber 1; Turn on vacuum pump 13 and adjust it to the standard test flow rate; Select the negative charge lung drug delivery mode by polarity switching switch, start the dual-mode gas phase single molecule drug delivery device, the drug liquid is electro-sprayed at the tip of the drug delivery tube 5 to form nano-micro charged droplets and sprayed directly, the device runs for 30 seconds according to the set parameters. After the experiment, the absorbent solutions in primary distribution bottle 11 and secondary distribution bottle 12 were collected and diluted to 50.0 mL with anhydrous ethanol. The absorbance was measured at a wavelength of 276 nm using a UV-Vis spectrophotometer, and the resulting UV absorption spectrum is shown below. Figure 7 As shown; The salbutamol content in the primary distribution bottle 11 and secondary distribution bottle 12 of the glass double-stage impactor was calculated based on the standard curve.

[0041] Depend on Figure 7 As can be seen, after the pulmonary nebulization drug delivery experiment, salbutamol was effectively delivered to the secondary distribution bottle 12, which simulated pulmonary deposition. The recovery rate of salbutamol in the primary distribution bottle 11 was 0.07 mg, accounting for 3.5% of the total dose; the recovery rate in the secondary distribution bottle 12 was 1.76 mg, accounting for 88.0% of the total dose; the overall recovery rate was 91.5%. A comparison of the pulmonary deposition efficiency of the device of this invention with that of a conventional nebulizer is provided. Figure 8 As shown.

[0042] Under the same experimental conditions, a comparative experiment was conducted using a traditional manual jet nebulizer. The results showed that the recovery volume of the primary distribution bottle 11 accounted for 42.5% of the total drug dosage, and the recovery volume of the secondary distribution bottle 12 accounted for 56.8% of the total drug dosage. A comparative experiment was conducted using a traditional ultrasonic jet nebulizer. The results showed that the recovery volume of the primary distribution bottle 11 accounted for 37.5% of the total drug dosage, and the recovery volume of the secondary distribution bottle 12 accounted for 61.8% of the total drug dosage.

[0043] This embodiment demonstrates that, using the negative-charge mode of the dual-mode gas-phase single-molecule drug delivery device described in this invention, the deposition efficiency of salbutamol in the simulated lung region can be increased to 88.0%, approximately 31.2 percentage points higher than that of traditional jet nebulizers. Simultaneously, the upper respiratory tract deposition rate is reduced from 42.5% to 3.5%. This verifies that the device of this invention, through the principle of like charges repelling each other in negative-charge spray and low-pressure nebulization, can significantly improve drug deposition efficiency in the lungs and reduce drug loss in the upper respiratory tract, providing an effective technical solution for achieving precise lung-targeted drug delivery.

[0044] Example 4 This embodiment aims to determine and compare the droplet size distribution of the drug solution produced by a traditional manual jet nebulizer, a traditional ultrasonic nebulizer, and the dual-mode gas-phase single-molecule drug delivery device shown in Example 1 using laser diffraction, in order to verify the technical advantages of the device of the present invention in generating fine droplets suitable for respiratory tract nebulization drug delivery.

[0045] In this embodiment, anhydrous ethanol was used as the solvent to prepare a salbutamol solution with a concentration of 1 mg / mL, which was used as the test solution for each nebulizer.

[0046] The devices under test in this embodiment are: Device A: a conventional manual jet nebulizer (control group A), Device B: a conventional ultrasonic nebulizer (control group B), and Device C: the dual-mode gas-phase single-molecule drug delivery device described in Example 1 (experimental group, negative charge mode). The operating parameters of the experimental group are set as follows: the bipolar electrospray circuit 6 outputs a reverse voltage of -1.2kV.

[0047] In this embodiment, laser diffraction was used to determine the droplet size distribution. A laser diffractometer was used for measurement, with a measurement range of 0.1 μm to 2000 μm, fully covering the 0.1 μm to 5 μm range of inhalable particles in the lungs. The nebulization flow rate was controlled by a vacuum pump 13. A high-speed camera was used to visualize and observe the entire nebulization process.

[0048] Each device was placed under identical environmental conditions (temperature 25±1℃, relative humidity 50±5%) to atomize the test solution. Each device was tested independently 5 times, with each spray lasting 30 seconds. Particle size distribution data were collected and the average value was analyzed.

[0049] The particle size distribution measurement results in this embodiment are as follows: Figure 9 As shown, the main particle size characteristic parameters are as follows: Control group A (traditional manual jet atomizer): The median volumetric particle size Dv50 was 5.8 ± 0.3 μm, and the particle size range ((Dv90-Dv10) / Dv50) was 2.4. Among them, droplets with a particle size greater than 10 μm accounted for 26% of the total volume, and droplets with a particle size in the range of 1 μm-5 μm accounted for 36%.

[0050] Control group B (traditional ultrasonic nebulizer): median volumetric particle size Dv50 was 3.6±0.2 μm, particle size range was 1.7, droplets with a particle size greater than 10 μm accounted for 11%, and droplets with a particle size in the range of 1μm-5 μm accounted for 55%.

[0051] Experimental group (device of the present invention): The median volumetric particle size Dv50 is 0.18±0.03 μm, the particle size span is 0.9, the proportion of droplets with a particle size greater than 1 μm is less than 2%, the proportion of droplets with a particle size less than 1 μm is more than 98%, and no droplets with a particle size greater than 10 μm are detected.

[0052] The experimental results of this embodiment show that, compared with traditional manual jet nebulizers and ultrasonic nebulizers, the dual-mode gas-phase single-molecule drug delivery device of this invention can generate nano- and micro-sized charged droplets with significantly smaller particle sizes and more concentrated distribution, with a median volume diameter (Dv50) of less than 0.2 μm. This particle size characteristic results in the vast majority of droplets generated by nebulization having extremely small aerodynamic diameters, making them easy to enter the deep respiratory tract with the airflow. This verifies the superiority of the device in terms of nebulization particle size control and is the physical basis for its efficient targeted drug delivery to the respiratory tract.

[0053] Example 5 This embodiment aims to systematically compare and evaluate the drug delivery effects of traditional manual jet nebulizers, traditional ultrasonic nebulizers, and the dual-mode gas phase single-molecule drug delivery device described in Example 1 by using a glass dual-stage impactor collection system that simulates human lung deposits and combining it with quantitative mass spectrometry analysis.

[0054] In this embodiment, the experimental setup uses a glass double-stage impactor to simulate human lung deposits, and combines it with a triple quadrupole mass spectrometer (equipped with a high-performance liquid chromatography injection system) for quantitative analysis.

[0055] The experimental drug used was salbutamol, and an anhydrous ethanol was used to prepare an experimental drug solution with a concentration of 1 mg / mL.

[0056] In this embodiment, the experimental parameters were set as follows: the output voltage of the bipolar electrospray circuit of the dual-mode gas-phase single-molecule drug delivery device (experimental group) was set to -1.2 kV (negative mode). The distance between the outlet end of the drug delivery tube 5 and the inlet of the dual-stage impactor was set to 5 cm; the inhalation flow rate of the vacuum pump 13 was set to 60 L / min; the single drug delivery volume was 2 mL; and the drug delivery duration was set to 30 seconds.

[0057] The drug administration effect determination in this embodiment includes the following steps: The experimental system was set up, and the outlet end of each atomizing device was fixed 5 cm away from the inlet of the dual-stage impactor. 7 mL of anhydrous ethanol was added to the primary distribution bottle 11 as the absorption solution, and 30 mL of anhydrous ethanol was added to the secondary distribution bottle 12 as the absorption solution. Add 2.0 mL of the test solution to each of the test devices; Turn on vacuum pump 13 and adjust the suction flow rate to 60 L / min; Turn on the atomizing device and spray continuously for 30 seconds; After the experiment, the absorbent solutions in the primary distribution bottle 11 and the secondary distribution bottle 12 of each group were combined and diluted to 50.0 mL with anhydrous ethanol. The diluted sample solution was injected into a high-performance liquid chromatography system and detected using an electrospray ionization source in positive ion mode. Quantitative analysis of salbutamol characteristic ion pairs was performed using multiple reaction monitoring (MRM) mode.

[0058] Figure 10 This image shows a comparison of the intensity of characteristic ion peaks of salbutamol in sample 12 of a secondary distribution bottle after collection by three different nebulizers using a glass double-stage impactor. Specific data are as follows: The mass spectrometry signal intensity of control group A (traditional manual jet nebulizer) is 1.8 × 10⁻⁶. 4 The mass spectrometry signal intensity of control group B (conventional ultrasonic nebulizer) was 3.2 × 10⁻⁶. 4 The mass spectrometry signal intensity of the experimental group (the device of this invention) was 1.5 × 10⁻⁶. 5 counts.

[0059] Figure 11 This is a bar chart comparing the recovery of salbutamol in the primary distribution bottle 11 and the secondary distribution bottle 12 in a simulated lung drug delivery experiment using the three nebulization devices in Embodiment 5 of the present invention.

[0060] In this embodiment, compared with traditional manual jet atomizers and ultrasonic atomizers, the mass spectrometry signal intensity of the device of the present invention is significantly higher and has better repeatability. The mass spectrometry signal intensity of the experimental group (the device of the present invention) is approximately 8.3 times that of control group A and 4.7 times that of control group B.

[0061] This embodiment demonstrates that the dual-mode gas-phase single-molecule drug delivery device described in this invention can achieve higher drug delivery efficiency and more stable drug delivery performance. Quantitative analysis using a glass bi-stage impactor combined with mass spectrometry shows that the amount of drug obtained by the device in the simulated lung deposition region is significantly higher than that of traditional nebulizers, verifying the technical advantages of this invention in improving lung drug delivery efficiency and stability.

[0062] In the description of this specification, references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0063] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this patent should be determined by the appended claims.

Claims

1. A dual-mode gas-phase single-molecule drug delivery device, characterized in that, The dual-mode gas-phase single-molecule drug delivery device includes a housing, an electronic control mechanism disposed inside the housing, and a drug delivery mechanism electrically connected to the electronic control mechanism. The housing includes an electrical control section for mounting the electrical control mechanism and a drug delivery section for accommodating the drug delivery mechanism; The electrical control mechanism includes a power supply component electrically connected to the drug delivery mechanism, and a control element for switching the power supply type of the power supply component; The power supply component is inserted into the drug delivery section to ionize the drug solution in the drug delivery section to form an electrospray. The control unit switches the drug delivery mode of the drug delivery mechanism by switching the positive and negative voltage states of the power supply component.

2. The dual-mode gas-phase single-molecule drug delivery device according to claim 1, characterized in that, The power supply assembly includes a power supply unit located at one end of the power control section, a circuit board electrically connected to the power supply unit, and an electrode rod electrically connected to the circuit board, with one end of the electrode rod away from the circuit board extending into the drug delivery section.

3. The dual-mode gas-phase single-molecule drug delivery device according to claim 2, characterized in that, The input terminal of the circuit board is used to connect to the power supply unit. The circuit board adopts a bipolar low-voltage drive structure with H-bridge inverter combined with symmetrical voltage doubler rectification to convert the power supply unit voltage into a preset low-voltage forward DC voltage and reverse DC voltage.

4. The dual-mode gas-phase single-molecule drug delivery device according to claim 3, characterized in that, The control unit is located at the end of the electrical control section away from the drug delivery section, and the control unit is used to switch the polarity of the output voltage of the circuit board.

5. The dual-mode gas-phase single-molecule drug delivery device according to claim 1, characterized in that, The drug delivery mechanism includes an external component connected to the drug delivery section and a drug delivery component disposed within the drug delivery section, with one end of the drug delivery component penetrating from the drug delivery section into the external component.

6. The dual-mode gas-phase single-molecule drug delivery device according to claim 5, characterized in that, The external assembly includes a sealing cover movably connected to the drug delivery section and an external pipe obliquely connected to the drug delivery section. The sealing cover and the drug delivery section enclose a drug storage chamber, and the drug delivery assembly passes through the external pipe.

7. The dual-mode gas-phase single-molecule drug delivery device according to claim 6, characterized in that, The drug delivery assembly includes a drug delivery tube connecting the external tube and the drug storage chamber, and a conductive needle passing through the drug delivery tube, with one end of the conductive needle away from the drug delivery tube connected to an electrode rod.

8. A dual-mode gas-phase single-molecule drug delivery system, characterized in that, Based on the dual-mode gas-phase single-molecule drug delivery device according to any one of claims 1-7, the system comprises: The first adjustment module is used to inject the drug solution into the drug storage chamber and adjust the distance between the drug delivery device and the recipient's face; The second adjustment module is used to determine the target area for drug delivery, turn on the circuit board, use the control unit to switch the polarity of the output voltage of the circuit board, adjust the charge-carrying capacity of the conductive needle, and form nano- and micro-charged droplets of corresponding polarity at the tip of the drug delivery tube, which are then directly sprayed onto the target area for drug delivery.

9. The dual-mode gas-phase single-molecule drug delivery system according to claim 8, characterized in that, In the step of using a control unit to switch the output voltage polarity of the circuit board and adjust the electrical charge carried by the conductive needle... If the target area for drug delivery is the throat, the circuit board is set to output a positive DC voltage so that the conductive needle carries a positive charge; If the target area for drug delivery is the lungs, a reverse DC voltage is set to be output so that the conductive needle carries a negative charge.

10. The dual-mode gas-phase single-molecule drug delivery system according to claim 9, characterized in that, The distance between the drug delivery device and the recipient's face is 1cm to 10cm. In the throat delivery mode, the distance can be adjusted to 1cm to 3cm; in the lung delivery mode, the distance can be adjusted to 3cm to 10cm.

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