Sound field driven microsphere lung targeted drug delivery device
By using a graded sound field and a sound field driving device with real-time targeted control, the problems of drug microsphere penetration of the mucus barrier and low targeting accuracy in existing technologies have been solved, achieving efficient, safe and precise delivery of drugs to the lungs.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- FUJIAN PROVINCIAL HOSPITAL
- Filing Date
- 2026-03-26
- Publication Date
- 2026-05-12
AI Technical Summary
Existing sound field-driven lung drug delivery devices cannot dynamically adjust driving parameters according to the physiological structure of different lung regions. Drug microspheres have difficulty penetrating the mucus barrier, resulting in low targeting accuracy and easy damage to normal lung tissue.
Employing a graded sound field structure, combined with surface-modified drug microspheres and a real-time targeted control module, the drug microspheres are driven in segments from the airway inlet to the lesion area, while an integrated temperature control and protection module prevents tissue damage.
It improves the lung penetration ability and targeting accuracy of drug microspheres, reduces deposition in non-lesion areas, and enhances the safety and ease of operation of drug delivery.
Smart Images
Figure CN122006091A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of lung-targeted drug delivery technology, specifically to a sound field-driven microsphere lung-targeted drug delivery device. Background Technology
[0002] Lung diseases are a group of diseases with high incidence and great difficulty in treatment. Traditional methods of lung drug administration mainly include oral administration, intravenous injection, and conventional inhalation. Oral and intravenous administration have problems such as low drug utilization and large systemic toxicity. The drug needs to pass through the systemic circulation to reach the lung lesion area, resulting in insufficient local drug concentration in the lungs and difficulty in achieving the ideal therapeutic effect. Conventional inhalation (such as nebulized inhalation) can deliver drugs directly into the airway, but it has defects such as low targeting accuracy, easy clearance of drugs by pulmonary mucociliary mucus, and insufficient delivery depth. It cannot accurately deliver to the deep lesion area of the lung, and drug microspheres tend to deposit on the airway surface, resulting in poor treatment effect.
[0003] With the development of acoustic field-driven technology, some acoustic field-driven lung drug delivery devices have emerged in the existing technology. Their core principle is to use the mechanical effect of an ultrasonic field to drive drug microspheres into the lungs. However, existing acoustic field-driven drug delivery devices still have significant technical shortcomings: 1. Using a single-frequency sound field drive, it is impossible to dynamically adjust the drive parameters according to the physiological structure of different areas of the lung (such as the airway mucus layer and alveolar regions), which makes it difficult for drug microspheres to penetrate the mucus barrier and easy to deposit in non-lesion areas. 2. The drug microspheres and the acoustic field drive lack synergistic adaptation. The surface of the microspheres has not been specifically modified, so they cannot achieve precise anchoring in the lesion area and are easily cleared by lung immune cells. 3. The lack of an effective targeting control mechanism makes it impossible to adjust the range and intensity of the sound field in real time according to the location of the lesion, resulting in low targeting accuracy; 4. During the sound field process, local overheating is easily generated, which may damage normal lung tissue, and there is a lack of effective temperature control and protection measures.
[0004] Chinese patent CN121466431A discloses a nebulized drug delivery device for targeted lung delivery of icariin. It uses airflow to achieve the screening and delivery of drug particles. However, the device does not use sound field drive and cannot break through the lung mucus barrier. The targeting accuracy depends on airflow screening, making it difficult to achieve precise drug delivery to deep lesion areas. Another study uses ultrasonic sound field to drive drug microspheres, but only uses a single frequency sound field, and the microspheres are not modified for mucus penetration and targeting, resulting in low drug delivery efficiency and poor targeting.
[0005] Therefore, developing a sound field-driven microsphere lung-targeted drug delivery device that can break through the lung mucus barrier, achieve precise targeting of lesion areas, and has safety protection functions has become an urgent need in the field of lung drug delivery technology. Summary of the Invention
[0006] To solve the above-mentioned technical problems, the technical solution provided by the present invention is as follows: According to an embodiment of the present invention, a sound field-driven microsphere lung-targeted drug delivery device includes a sound field generating module, a microsphere storage and drug delivery module, a targeting control module, and a temperature control and protection module, all of which are electrically connected via connecting wires. The sound field generating module has a graded sound field structure, including a low-frequency sound field generator and a high-frequency sound field generator, which can output a graded sound field with adjustable gradient to achieve segmented driving of the drug microspheres from the airway inlet to the lung lesion area. The microsphere storage and drug delivery module contains drug microspheres with surfaces modified with lung-targeting ligands and mucus-penetrating units. The lung-targeting ligands are lung epithelial cell-specific binding ligands, and the mucus-penetrating units are hydrophilic polymer modification layers. The targeting control module includes a lesion location detector, a signal processor, and a parameter control unit, which can collect lung lesion location signals in real time and dynamically adjust the frequency, intensity, and duration of action of the sound field generating module. The temperature control and protection module includes a temperature sensor and a temperature controller, which can monitor the temperature of the sound field action area in real time and maintain it within a safe range.
[0007] The low-frequency sound field generator has a frequency range of 10-50kHz and an intensity of 0.1-0.5W / cm², and is used to drive the drug microspheres to penetrate the lung mucus layer; the high-frequency sound field generator has a frequency range of 100-500kHz and an intensity of 0.05-0.2W / cm², and is used to precisely push the drug microspheres to the lesion area, and the effective range of the high-frequency sound field can be focused and adjusted by the parameter control unit.
[0008] The drug microspheres have a particle size of 1-5 μm, the surface-modified lung-targeting ligand is a receptor-specific antibody on the surface of alveolar epithelial cells, the mucus-penetrating unit is a polyethylene glycol (PEG) modified layer, the drug microspheres encapsulate lung therapeutic drugs, and the outer shell of the microspheres is an ultrasound-responsive material that can slowly release drugs under the action of graded sound fields.
[0009] The lesion location detector is a portable lung ultrasound detector, which can collect the location coordinates and lesion range signals of the lung lesion area in real time. The signal processor converts the collected signals into electrical signals and transmits them to the parameter control unit to realize the automatic adjustment of the sound field parameters. The adjustment response time is ≤0.5s.
[0010] The sound field generating module also includes a sound field conduction probe, which has an arc-shaped structure that conforms to the contours of the human face and neck. It can conduct graded sound fields directionally to the airway inlet, reducing sound field energy loss. The surface of the sound field conduction probe is coated with a biocompatible coating.
[0011] Furthermore, the temperature sensor of the temperature control and protection module is located at the sound field conduction probe, which can monitor the surface temperature of the lung airway in real time, with a monitoring range of 36-40℃. When the temperature exceeds 37.5℃, the temperature controller automatically reduces the sound field intensity until the temperature returns to a safe range.
[0012] The microsphere storage and drug delivery module also includes a quantitative drug delivery valve and a microsphere delivery tube. The quantitative drug delivery valve can accurately control the number of microspheres administered in a single dose with a control accuracy of ±5%. The outlet of the microsphere delivery tube is connected to the face mask, and the inner wall of the delivery tube is provided with an anti-adhesion coating to prevent the drug microspheres from adhering and clogging.
[0013] The targeted regulation module also includes a human-computer interaction interface, which allows manual setting of sound field parameters, drug dosage and drug administration time, while displaying lesion location, sound field parameters and temperature data in real time, facilitating monitoring by operators.
[0014] The temperature controller uses semiconductor temperature control technology with a temperature control accuracy of ±0.1℃. It can be adjusted in real time according to the feedback signal from the temperature sensor to avoid lung tissue damage caused by the sound field.
[0015] The drug delivery device is a portable device weighing ≤500g. It can be powered by a rechargeable battery with a battery life of ≥4h, and is suitable for clinical bedside drug delivery and home long-term care drug delivery.
[0016] The advantages of this invention compared to the prior art are: 1. A graded sound field collaborative driving structure is adopted, with low-frequency sound field used to penetrate the lung mucus layer and high-frequency sound field used to precisely push the drug microspheres to the lesion area, realizing segmented driving of drug microspheres from the airway inlet to the lesion area, improving the lung penetration ability and deposition rate of drug microspheres; 2. Achieving synergistic adaptation between drug microspheres and acoustic field drive, the microsphere surface is modified with lung-targeting ligands and mucus-penetrating units, which can not only quickly penetrate the mucus layer, but also accurately anchor the lung lesion area, avoiding the microspheres being cleared by lung mucus or deposited in non-lesion areas, thus significantly improving targeting accuracy; 3. A real-time targeted control module has been added, which can dynamically adjust the sound field parameters according to the location of lung lesions, so as to achieve precise matching between the sound field range and the lesion area. It has a fast response speed, is easy to operate, and is suitable for lung lesions in different locations and ranges. 4. An integrated temperature control and protection module is used. The temperature sensor is located at the sound field conduction probe to monitor the temperature of the sound field area in real time and perform precise temperature control to avoid local overheating and damage to normal lung tissue, thereby improving the safety of the drug administration process and reducing the risk of adverse reactions during drug administration. 5. The overall design is portable, lightweight, and has a long battery life. Powered by a rechargeable battery, it is suitable for clinical bedside administration and home long-term care administration. It is easy to operate and does not require full-time operation by professionals, which improves patient medication adherence and has broad clinical application prospects. Attached Figure Description
[0017] Figure 1 This is a schematic diagram of the overall structure and working process of the acoustic field driven microsphere lung-targeted drug delivery device of the present invention; Figure 2 This is a schematic diagram of the sound field generation module of the sound field driven microsphere lung-targeted drug delivery device of the present invention; Figure 3 This is a schematic diagram of the microsphere storage and drug delivery module of the acoustic field driven microsphere lung-targeted drug delivery device of the present invention.
[0018] Figure label: 1-Sound field generation module, 11-Low frequency sound field generator, 12-High frequency sound field generator, 13-Sound field conduction probe; 2-Microsphere storage and drug delivery module, 21-Drug microspheres, 22-Quantitative drug delivery valve, 23-Microsphere delivery tube, 24-Microsphere storage chamber; 3-Targeted regulation module, 31-Lesion location detector, 32-Signal processor, 33-Parameter regulation unit, 34-Human-machine interface; 4-Temperature control and protection module, 41-Temperature sensor, 42-Temperature controller; 5- Rechargeable battery. Detailed Implementation
[0019] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, 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. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.
[0020] Example: A sound field-driven microsphere lung-targeted drug delivery device according to an embodiment of the present invention, such as... Figure 1-3As shown, specifically, it includes a sound field generating module 1, a microsphere storage and drug delivery module 2, a targeted regulation module 3, and a temperature control and protection module 4. Each module is electrically connected via a connecting wire and is powered by a rechargeable battery 5. The battery life is ≥4 hours, and the overall weight is 450g, making it easy to carry.
[0021] The sound field generating module 1 includes a low-frequency sound field generator 11, a high-frequency sound field generator 12, and a sound field conduction probe 13. The low-frequency sound field generator 11 has a frequency set to 30kHz and an intensity set to 0.3W / cm². The high-frequency sound field generator 12 has a frequency set to 300kHz and an intensity set to 0.1W / cm². The sound field conduction probe 13 has an arc-shaped structure that conforms to the contours of the human face and neck. Its surface is coated with a medical-grade silicone biocompatible coating to reduce skin irritation and improve sound field conduction efficiency.
[0022] The microsphere storage and drug delivery module 2 includes drug microspheres 21, a quantitative drug delivery valve 22, and a microsphere delivery tube 23. The drug microspheres 21 are stored in a microsphere storage chamber 24. The particle size of the drug microspheres 21 is 3 μm. Each drug microsphere 21 includes a microsphere shell, a drug core, a lung-targeting ligand, and a mucus penetration unit. The microsphere shell is made of polylactic-co-glycolic acid copolymer (PLGA) ultrasound-responsive material. The drug core is gefitinib, a drug for treating lung cancer. The lung-targeting ligand is an EGFR receptor-specific antibody on the surface of alveolar epithelial cells. The mucus penetration unit is a PEG-2000 modified layer. The quantitative drug delivery valve 22 is set to a single dose of 10 mg with a control accuracy of ±5%. The inner wall of the microsphere delivery tube 23 is coated with a polytetrafluoroethylene anti-adhesion coating, and the outlet is connected to a face mask to ensure smooth delivery of the drug microspheres 21.
[0023] The targeted regulation module 3 includes a lesion location detector 31, a signal processor 32, a parameter regulation unit 33, and a human-machine interface 34. The lesion location detector 31 is a portable lung ultrasound detector with a detection depth of 5-10 cm, which can collect the location coordinates of the lung lesion area in real time. The signal processor 32 uses an STM32 microcontroller to convert ultrasound signals into electrical signals and perform analysis and processing. The parameter regulation unit 33 dynamically adjusts the frequency and intensity of the low-frequency and high-frequency sound fields according to the instructions of the signal processor 32, with an adjustment response time of 0.3 s. The human-machine interface 34 is a touch screen display, which allows manual setting of drug administration parameters and real-time display of lesion location, sound field parameters, and temperature data.
[0024] The temperature control and protection module 4 includes a temperature sensor 41 and a temperature controller 42. The temperature sensor 41 is a thermistor sensor, which is located inside the sound field conduction probe 13 and has a monitoring range of 36-40℃. The temperature controller 42 uses a semiconductor temperature control chip with a temperature control accuracy of ±0.1℃. When the detected temperature exceeds 37.5℃, it automatically reduces the intensity of the high-frequency sound field generator 12 until the temperature returns to below 37℃.
[0025] The working process of the acoustic field-driven microsphere lung-targeted drug delivery device is as follows: (1) Preoperative preparation: Place the drug microspheres 21 into the microsphere storage chamber 24, set the single dose to 10mg through the human-computer interaction interface 34, set the initial values of the sound field parameters (low frequency 30kHz, intensity 0.3W / cm², high frequency 300kHz, intensity 0.1W / cm²), set the temperature control safety threshold to 37.5℃, and ensure that the rechargeable battery 5 has sufficient power. (2) Lesion localization: The lesion location detector 31 is placed close to the patient's chest to collect the location coordinates of the lung cancer lesion area in real time. The signal processor 32 analyzes and processes the collected signals to determine the specific location and range of the lesion area and transmits the signals to the parameter control unit 33. (3) Graded sound field driven drug delivery: The parameter control unit 33 adjusts the parameters of the sound field generation module 1 according to the lesion location signal, so that the low frequency sound field is focused on the airway mucus layer, driving the drug microspheres 21 to penetrate the mucus layer; at the same time, the high frequency sound field is adjusted to focus on the lesion area, and the drug microspheres 21 are precisely pushed to the lesion location. The lung targeting ligand on the surface of the drug microspheres 21 specifically binds to the alveolar epithelial cells in the lesion area to achieve targeted anchoring. (4) Temperature monitoring: Temperature sensor 41 monitors the temperature of the sound field area in real time. When the temperature exceeds 37.5℃, temperature controller 42 automatically reduces the intensity of high-frequency sound field until the temperature returns to a safe range. During the drug administration process, the operator monitors various parameters in real time through human-machine interface 34 to ensure drug administration safety. (5) End of drug administration: After drug administration is completed, turn off the sound field generation module 1, clean the microsphere storage chamber 24 and the microsphere delivery tube 23 to complete the entire drug administration process.
[0026] The present invention and its embodiments have been described above. This description is not restrictive, and the accompanying drawings are only one embodiment of the present invention; the actual structure is not limited thereto. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the invention, such designs should fall within the protection scope of the present invention.
Claims
1. A sound field-driven microsphere lung-targeted drug delivery device, characterized in that, The system includes a sound field generation module (1), a microsphere storage and drug delivery module (2), a targeting and control module (3), and a temperature control and protection module (4), all of which are electrically connected via connecting wires. The sound field generation module (1) is a graded sound field structure, including a low-frequency sound field generator (11) and a high-frequency sound field generator (12), which can output a graded sound field with adjustable gradient to realize the segmented driving of drug microspheres from the airway inlet to the lung lesion area. The microsphere storage and drug delivery module (2) is loaded with drug microspheres (21) whose surfaces are modified with lung-targeting ligands and mucus penetration units. The lung-targeting ligand is a lung epithelial cell-specific binding ligand, and the mucus penetration unit is a hydrophilic polymer modification layer; the targeting regulation module (3) includes a lesion location detector (31), a signal processor (32) and a parameter regulation unit (33), which can collect lung lesion location signals in real time and dynamically adjust the frequency, intensity and duration of the sound field generation module (1); the temperature control and protection module (4) includes a temperature sensor (41) and a temperature controller (42), which can monitor the temperature of the sound field action area in real time and maintain it within a safe range.
2. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The low-frequency sound field generator (11) has a frequency range of 10-50kHz and an intensity of 0.1-0.5W / cm², and is used to drive the drug microspheres (21) to penetrate the lung mucus layer; the high-frequency sound field generator (12) has a frequency range of 100-500kHz and an intensity of 0.05-0.2W / cm², and is used to precisely push the drug microspheres (21) to the lesion area, and the effective range of the high-frequency sound field can be focused and adjusted by the parameter control unit (33).
3. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The drug microspheres (21) have a particle size of 1-5 μm, the lung-targeting ligand modified on the surface is a specific antibody against the receptor on the surface of alveolar epithelial cells, the mucus-penetrating unit is a polyethylene glycol (PEG) modified layer, the drug microspheres (21) encapsulate lung therapeutic drugs, and the outer shell of the microspheres is an ultrasound-responsive material that can slowly release drugs under the action of graded sound fields.
4. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The lesion location detector (31) is a portable lung ultrasound detector that can collect the location coordinates and lesion range signals of the lung lesion area in real time. The signal processor (32) converts the collected signals into electrical signals and transmits them to the parameter control unit (33) to realize the automatic adjustment of the sound field parameters. The adjustment response time is ≤0.5s.
5. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The sound field generating module (1) also includes a sound field transmission probe (13). The sound field transmission probe (13) has an arc-shaped structure that fits the contours of the human face and neck. It can conduct graded sound fields to the airway inlet in a directional manner, reducing sound field energy loss. The surface of the sound field transmission probe (13) is provided with a biocompatible coating.
6. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 5, characterized in that, The temperature sensor (41) of the temperature control and protection module (4) is located at the sound field conduction probe (13), which can monitor the surface temperature of the lung airway in real time. The monitoring range is 36-40℃. When the temperature exceeds 37.5℃, the temperature controller (42) automatically reduces the sound field intensity until the temperature returns to a safe range.
7. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The microsphere storage and drug delivery module (2) also includes a quantitative drug delivery valve (22) and a microsphere delivery tube (23). The quantitative drug delivery valve (22) can accurately control the number of microspheres administered in a single dose, with a control accuracy of ±5%. The outlet of the microsphere delivery tube (23) is connected to the face mask, and the inner wall of the delivery tube is provided with an anti-adhesion coating to prevent the drug microspheres (21) from adhering and clogging.
8. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The targeted regulation module (3) also includes a human-computer interaction interface (34), which allows manual setting of sound field parameters, drug dosage and drug administration time, while displaying the lesion location, sound field parameters and temperature data in real time, making it convenient for operators to monitor.
9. The acoustic field-driven microsphere lung-targeted drug delivery device according to claim 1, characterized in that, The temperature controller (42) adopts semiconductor temperature control technology and has a temperature control accuracy of ±0.1℃. It can be adjusted in real time according to the feedback signal of the temperature sensor (41) to avoid lung tissue damage caused by the sound field.
10. A sound field-driven microsphere lung-targeted drug delivery device according to any one of claims 1-9, characterized in that, The drug delivery device is a portable device with a weight of ≤500g. It can be powered by a rechargeable battery (5) with a battery life of ≥4h. It is suitable for clinical bedside drug delivery and home long-term care drug delivery.