Nanoparticle drug carrier preparation device and use method

Abstract

The invention belongs to the technical field of nano medicament preparation, and discloses a nanoparticle drug carrier preparation device and a use method, and the method comprises the following steps: a motor drives an emulsification mechanism and a rotary drum to reversely rotate, and preliminary emulsification is carried out; the rotation driver drives the two stirring shafts and the stirring blades to rotate; the wall scraping assembly continuously scrapes materials on the inner wall of the rotary drum, and it is guaranteed that the materials are fully mixed; the comprehensive analysis and evaluation module fuses the multi-source information and comprehensively evaluates the preparation process of the nanoparticle drug carrier; according to the comprehensive evaluation result, whether the preparation parameters need to be adjusted or not is judged; adjusting the parameters as required; and conveying the materials in the rotary drum into a high-pressure homogenizer for homogenizing treatment to obtain the nanoparticle drug carrier. The emulsifying and stirring effects are improved through combination of multiple modes, and the uniformity of a nanoparticle drug carrier is guaranteed; comprehensive monitoring is achieved, various information is fused, historical data are combined, comprehensive evaluation and risk prediction are conducted on the preparation process, and preparation parameters are adjusted.

Description

Technical Field

[0001] This application relates to the technical field of nanoparticle drug preparation, and more specifically, to a nanoparticle drug carrier preparation device and its usage method. Background Art

[0002] Nanopharmaceuticals are a new type of drug dosage form, which uses nanotechnology to process drug active ingredients or drug carriers into nanoparticles, nanoemulsions, nanomicelles, nanoliposomes, etc. Compared with traditional drug dosage forms, nanopharmaceuticals have many advantages: improving drug solubility, many drugs have poor solubility problems, after being made into nanopharmaceuticals, the specific surface area of the drug increases, and the solubility is significantly improved, thus enhancing the bioavailability of the drug. Improving targeting, by modifying the nanoparticle drug carrier, it can specifically recognize cells or tissues at the lesion site and achieve targeted drug delivery. Taking tumor treatment as an example, nanopharmaceuticals can accurately accumulate in tumor tissues, increase the drug concentration at the tumor site, and reduce the toxic and side effects on normal tissues.

[0003] The prior art document with the publication number CN113680235A provides a preparation device for nanopharmaceuticals, including a cylinder body with a chassis, a ring plate is rotatably connected to the top of the cylinder body, two emulsifying mechanisms are arranged inside the ring plate, each emulsifying mechanism includes a first motor, a stirring shaft and an electric push rod, limiting grooves are opened on both sides of the stirring shaft, limiting pieces are slidably connected in the limiting grooves, a plurality of stirring blades are also fixed on the outer side of the stirring shaft, the telescopic shaft of the electric push rod extends into the cylinder body, and the bottom end of the telescopic shaft is fixed with a collar, and the collar is rotatably connected to the outer side of the stirring shaft near the top. By rotatably connecting a ring plate to the top of the cylinder body, when the ring plate rotates on the top of the cylinder body, it can drive the horizontal position adjustment of the emulsifying mechanism, and the mixing uniformity of the materials in the cylinder body is better when combined with the vertical stirring effect. The electric push rod can drive the stirring shaft to be adjusted in the vertical space, and different amounts of materials are mixed and used, increasing the uniform distribution of the materials.

[0004] Although the above prior art solutions can achieve relevant beneficial effects through the structures of the prior art, there are still the following defects: 1. The prior art only adopts a single stirring method, resulting in insufficient emulsification of the materials, making it difficult to ensure the uniformity of the nanoparticle drug carrier and affecting the product quality. 2. The prior art cannot comprehensively evaluate the preparation process and predict risks, and it is also difficult to adjust the preparation parameters according to the evaluation results. This will cause the preparation process to not always be in the best state, and the defective rate is relatively high. 3. It is unable to effectively scrape the materials on the inner wall of the cylinder, resulting in uneven mixing of the materials, affecting the emulsification effect and the particle size uniformity and quality stability of the nanoparticles.

[0005] In view of this, we propose a nanoparticle drug carrier preparation device and its usage method. Summary of the Invention

[0006] 1. Technical issues to be solved

[0007] The purpose of the present application is to provide a nanoparticle drug carrier preparation device and a method for use, which solves the technical problems raised in the above-mentioned background technology, realizes preliminary emulsification by driving the emulsification mechanism and the rotating drum to rotate in reverse by a motor, and then uses the rotation drive to drive the stirring shaft to rotate synchronously, as well as the cavitation effect of the ultrasonic generator. The combination of multiple methods greatly improves the emulsification and stirring effect, so that the material can be fully emulsified and dispersed, and the uniformity of the nanoparticle drug carrier is ensured; comprehensive monitoring can be achieved, and the comprehensive analysis and evaluation module integrates multiple information and combines historical data to conduct a comprehensive evaluation and risk prediction of the preparation process, and adjusts the preparation parameters according to the evaluation results to ensure that the preparation process is always in the best state and improve the technical effect of product quality.

[0008] 2. Technical solution.

[0009] The technical solution of the present application provides a device for preparing nanoparticle drug carriers, including an emulsification barrel, a barrel cover, a rotating drum, an emulsification mechanism, a wall scraping assembly, a driving gear, a transmission gear, a motor A, an ultrasonic probe, a high-pressure homogenizer, a suction pump and a monitoring mechanism.

[0010] A rotating drum is rotatably arranged in the emulsifying barrel; a motor is fixedly arranged at the bottom of the emulsifying barrel, the output shaft of the motor extends into the emulsifying barrel, and the output shaft of the motor is detachably fixedly connected with the emulsifying mechanism.

[0011] The bottom of the emulsifying barrel is rotatably provided with a transmission gear; the output shaft of the motor is coaxially fixed with a driving gear, and the bottom of the drum is fixed with a gear ring; the transmission gear is meshed and connected with the driving gear and the gear ring respectively. The motor can drive the drum to rotate through the transmission gear, the driving gear and the gear ring, and the rotation direction of the drum is opposite to that of the emulsifying mechanism. The function of the drum is to contain the material to be emulsified, and to work with the emulsifying mechanism during the rotation process to promote the full mixing and emulsification of the material.

[0012] A wall scraping component is detachably fixedly arranged on the emulsifying mechanism.

[0013] The barrel cover and the rotating drum are sealingly rotatably connected; the barrel cover is detachably fixedly arranged on the upper end of the emulsifying barrel; an ultrasonic probe is arranged on the barrel cover, and the ultrasonic probe is connected to the ultrasonic generator.

[0014] A suction pump is fixedly arranged on the high-pressure homogenizer, and an input end of the suction pump is arranged on the barrel cover. The input end of the suction pump passes through the barrel cover and extends into the bottom of the rotating drum.

[0015] A monitoring mechanism is fixedly arranged on the barrel cover; the monitoring mechanism monitors and regulates the preparation process of the nanoparticle drug carrier.

[0016] Through the above technical solution, the materials for the nanoparticle drug carrier to be prepared are added into the rotating cylinder. The barrel cover is covered, the motor is started, the motor drives the emulsifying mechanism to rotate, and at the same time, by driving the rotating cylinder to rotate in the reverse direction, the preliminary emulsification of the materials begins. The ultrasonic generator is started, and the ultrasonic probe emits ultrasonic waves into the materials, and the cavitation effect is used to further promote the emulsification and dispersion of the materials. During the emulsification process, the scraping wall assembly continuously scrapes off the materials on the inner wall of the rotating cylinder to ensure the full mixing of the materials. The monitoring mechanism monitors various parameters during the preparation process in real time and adjusts them as needed. When the preliminary emulsification is completed, the suction pump is started to transport the materials in the rotating cylinder to the high-pressure homogenizer for homogenization treatment. The materials after being processed by the high-pressure homogenizer are the required nanoparticle drug carrier. The real-time monitoring and adjustment functions of the monitoring mechanism ensure the stability of the preparation process and the consistency of the product quality.

[0017] As an alternative embodiment of the present invention, a plurality of emulsifying pumps are connected and arranged on the barrel cover through hoses; flow control valves are arranged on the hoses.

[0018] The input ends of the emulsifying pumps all extend into the water storage tank, the drug storage tank and the solvent storage tank. Water, drugs and solvents are stored in the water storage tank, the drug storage tank and the solvent storage tank respectively. By adjusting the opening degree of the flow control valve, the conveying flow rates of water, drug raw materials and solvents are accurately controlled.

[0019] An oil storage tank is connected and arranged on the barrel cover through a hose, an oil pump is fixedly arranged on the oil storage tank, and the input end of the oil pump extends to the bottom of the oil storage tank. An oil phase is stored in the oil storage tank. A suitable oil phase is selected according to the properties of the drug such as solubility, stability and pharmacological activity.

[0020] As an alternative embodiment of the present invention, a plurality of dial blocks are evenly distributed on the inner wall of the rotating cylinder to improve the emulsification effect. The shapes of the dial blocks can be rectangular, trapezoidal, triangular, etc. Different-shaped dial blocks will produce different hydrodynamic effects when stirring the materials. The material of the dial blocks is stainless steel.

[0021] Through the above technical solution, when the dial blocks pass through the materials, the original laminar flow state of the materials will be destroyed, causing the materials to generate strong turbulence. Turbulence can increase the collision and mixing opportunities between different components in the materials and promote the dispersion and emulsification of the oil phase and the water phase.

[0022] As an alternative embodiment of the present invention, the emulsifying mechanism includes a rotating base, a stirring shaft, stirring blades and a rotation drive.

[0023] The rotating base is detachably and fixedly arranged on the output shaft of the motor; two stirring shafts are rotatably arranged on the rotating base; a number of stirring blades are arranged on the stirring shafts in a staggered manner.

[0024] A rotation drive is fixedly arranged on the rotating base; the rotation drive is in transmission connection with the stirring shaft.

[0025] Through the above technical solution, while the motor drives the rotating seat and the stirring shaft to revolve, the two stirring shafts are driven to rotate by the rotation drive, and the stirring shaft drives the stirring blades to rotate, thereby improving the emulsification uniformity effect.

[0026] As an optional solution of the present invention, the rotation drive includes a motor B, a driving gear, a shaft, a driven gear and a bevel gear B.

[0027] A motor B is fixedly arranged on the rotating seat; a driving gear is coaxially fixedly arranged on the output end of the motor B; a shaft rod is rotatably arranged on the rotating seat, and a driven gear is coaxially fixedly arranged on the shaft rod; the driven gear is meshed and transmission-connected with the driving gear.

[0028] Bevel gears B are coaxially fixedly arranged at both ends of the shaft, and a bevel gear A is coaxially fixedly arranged on the stirring shaft; the bevel gear A and the bevel gear B are meshed and transmission-connected.

[0029] Through the above technical solution, the starting motor B drives the driving gear to rotate, the driving gear drives the driven gear and the shaft to rotate, the shaft drives the bevel gear B to rotate, and the bevel gear B drives the bevel gear A to rotate, thereby driving the two stirring shafts to rotate synchronously, thereby improving the emulsification stirring effect.

[0030] As an optional solution of the present invention, the wall scraping assembly includes a rotating plate, a sliding block and a scraping plate.

[0031] The rotating plate is detachably fixed on the rotating seat of the emulsifying mechanism; sliders are slidably arranged at both ends of the rotating plate; a spring is arranged between the slider and the rotating plate; a scraper is fixedly arranged at the other end of the slider, and the scraper is arranged in friction contact with the inner wall of the rotating drum.

[0032] As an optional solution of the present invention, a heating plate is fixedly arranged at the bottom of the rotating drum, and a temperature sensor is fixedly arranged on the rotating drum.

[0033] As an optional solution of the present invention, a concentration sensor, a liquid level sensor, a pressure sensor and a particle size analyzer are arranged on the barrel cover.

[0034] As an optional solution of the present invention, a pressure regulating device is connected to the barrel cover.

[0035] As an optional solution of the present invention, the monitoring mechanism includes:

[0036] Data collection module: collects a large amount of data on materials, temperature, pressure, concentration, etc. used in the preparation of nanoparticle drug carriers. Widely collects various key data involved in the preparation of nanoparticle drug carriers. Labels the collected data.

[0037] Temperature monitoring module: including temperature sensor, which monitors the temperature of the emulsion in the drum in real time.

[0038] Pressure monitoring module: It includes a pressure sensor to monitor the pressure inside the rotating drum in real time.

[0039] Particle size analyzer: It monitors the particle size of the nanoparticles.

[0040] Liquid level monitoring module: It includes a liquid level sensor to monitor the liquid level height inside the rotating drum in real time.

[0041] Comprehensive analysis and evaluation module: It integrates information such as aqueous phase, oil phase, solvent, temperature, pressure, and particle size, comprehensively evaluates the preparation process of the rice grain drug carrier, and adjusts the parameters as needed. It promptly discovers abnormal situations. It includes information fusion evaluation and parameter adjustment decision-making.

[0042] Information fusion evaluation: This module conducts fusion analysis on information such as the types and dosages of the aqueous phase, oil phase, and solvent, as well as temperature, pressure, and particle size. By establishing a mathematical model and data analysis algorithm, it comprehensively evaluates the overall situation of the preparation process of the nanoparticles drug carrier. For example, it analyzes the influence of different material combinations on the particle size and stability of the nanoparticles under specific temperature and pressure conditions, so as to judge whether the preparation process is in the optimal state.

[0043] Parameter adjustment decision-making: According to the comprehensive evaluation results, this module can judge whether it is necessary to adjust the preparation parameters. If it is found that some parameters deviate from the optimal range, it will send a suggestion to the control center. The control center will automatically or prompt the operator to manually adjust the relevant parameters and feedback the abnormal information to the control center.

[0044] Alarm module: It includes an alarm. When an abnormal situation is detected, it promptly issues an alarm.

[0045] Control center: It is network-connected to the data collection module, temperature monitoring module, flow control valve, pressure monitoring module, particle size analyzer, liquid level monitoring module, and comprehensive analysis and evaluation module.

[0046] As an alternative solution of the present invention, the comprehensive analysis and evaluation module: It integrates information such as aqueous phase, oil phase, solvent, temperature, pressure, and particle size, comprehensively evaluates the preparation process of the rice grain drug carrier, and adjusts the parameters as needed. It promptly discovers abnormal situations. It includes the following steps:

[0047] 1. Data preprocessing: Obtain information on the types and dosages of the aqueous phase, oil phase, and solvent, as well as temperature data from the temperature monitoring module, pressure data from the pressure monitoring module, particle size data from the particle size analyzer, etc. from the data collection module. Perform data cleaning to remove duplicate, incorrect, or invalid data, and standardize the collected data to make different types of data comparable. Conduct data integration to integrate the processed data according to the time series or preparation batches to form a complete dataset for subsequent analysis.

[0048] 2. Establish a mathematical model: Select a multiple linear regression model according to the characteristics and requirements of nanoparticle drug carrier preparation. Use historical data to train the selected model and determine the model parameters. Continuously adjust the model parameters to enable the model to accurately reflect the relationships between various factors in the preparation process. Model verification: Use a portion of the data that was not involved in training to verify the established model and evaluate the accuracy and reliability of the model. If the prediction results of the model deviate significantly from the actual situation, the model needs to be adjusted and optimized.

[0049] 3. Data analysis;

[0050] Feature extraction: Extract features related to the nanoparticle preparation process from the integrated dataset, such as the ratios of different material combinations, the changing trends of temperature and pressure, the distribution characteristics of particle size, etc. These features will be used as the input of the model for analyzing and evaluating the preparation process.

[0051] Model calculation: Input the extracted features into the established mathematical model for calculation and analysis. The model will predict key indicators such as the particle size and stability of the nanoparticles based on the input features and compare them with the preset target values.

[0052] 4. Comprehensive evaluation: Based on the calculation results of the model, comprehensively consider factors such as the aqueous phase, oil phase, solvent, temperature, pressure, and particle size to evaluate the overall situation of the nanoparticle drug carrier preparation process. Determine whether the preparation process is in the optimal state. Combine historical data to predict whether there are potential problems or risks.

[0053] 5. Parameter adjustment decision:

[0054] 5.1. Judge the deviation of parameters: Set reasonable threshold ranges for each parameter according to the process requirements and quality standards of nanoparticle drug carrier preparation. Compare the parameter values calculated by the model with the set threshold ranges to determine whether there are parameter deviations. If a certain parameter exceeds the threshold range, it is considered that the parameter is abnormal. For the parameters that deviate from the threshold range, further evaluate the degree of abnormality. Make a comprehensive evaluation based on factors such as the deviation amplitude and duration to judge the severity of the abnormal situation.

[0055] 5.2. Generating adjustment suggestions: When parameter deviation is detected, use the established mathematical model and data analysis algorithm to analyze the reasons for the parameter deviation. For example, if the particle size suddenly increases, it may be caused by factors such as too high temperature, unstable pressure, or imbalance in the material ratio.

[0056] Formulate an adjustment strategy. Based on the results of the cause analysis, formulate corresponding parameter adjustment strategies. For example, if the increase in particle size is caused by too high temperature, it can be recommended to reduce the power of the heating equipment; if it is due to imbalance in the material ratio, it can be recommended to adjust the flow control valve to change the feeding ratio.

[0057] Convert the formulated adjustment strategy into specific adjustment suggestions, including the name of the parameter to be adjusted, the adjustment direction, and the adjustment amplitude, etc.

[0058] 5.3. Feedback and execution: Send the generated adjustment suggestions to the control center, and at the same time, also feedback the abnormal situations and relevant data found during the preparation process to the control center. The control center selects to automatically or prompt the operator to manually adjust the relevant parameters according to the received adjustment suggestions. If automatic adjustment is selected, the control center will automatically control the corresponding equipment to adjust the parameters according to the suggestions; if manual adjustment is selected, the control center will prompt the operator to operate according to the suggestions and provide necessary operation guidance. After the parameter adjustment, continuously monitor various parameters of the preparation process and the quality indicators of the nanoparticles, and evaluate the effect of the adjustment. If the parameters still deviate or do not reach the expected effect after adjustment, it is necessary to re - analyze and adjust until the preparation process returns to the optimal state.

[0059] The present invention provides a method for using a nanoparticle drug carrier preparation device, including the following steps:

[0060] S1. Add the materials for preparing the nanoparticle drug carrier into the rotating drum. Cover the drum lid, and the heating plate at the bottom inside the rotating drum heats the materials to a predetermined temperature. Start the motor, and the motor drives the emulsifying mechanism to rotate, while driving the rotating drum to rotate in the opposite direction, and start the preliminary emulsification of the materials.

[0061] S2. The motor B driven by rotation drives the driving gear to rotate, the driving gear drives the driven gear and the shaft rod to rotate, the shaft rod drives the bevel gear B to rotate, and the bevel gear B drives the bevel gear A to rotate, thereby driving the two stirring shafts and the stirring blades to rotate synchronously, improving the emulsification and stirring effect.

[0062] S3. Start the ultrasonic generator, and the ultrasonic probe emits ultrasonic waves into the materials, and use the cavitation effect to further promote the emulsification and dispersion of the materials. During the emulsification process, the scraping wall assembly continuously scrapes off the materials on the inner wall of the rotating drum to ensure the full mixing of the materials.

[0063] S4. The temperature monitoring module monitors the temperature of the emulsion in the rotating drum in real time; the pressure monitoring module monitors the pressure in the rotating drum in real time; the particle size analyzer monitors the particle size of the nanoparticles; the liquid level monitoring module monitors the liquid level height in the rotating drum in real time.

[0064] S5. The comprehensive analysis and evaluation module of the monitoring mechanism integrates information such as aqueous phase, oil phase, solvent, temperature, pressure, and particle size, comprehensively evaluates the preparation process of the rice grain drug carrier, combines historical data, and predicts whether there are potential problems or risks. Abnormal situations are detected in a timely manner.

[0065] S6. According to the comprehensive evaluation results, it is judged whether the preparation parameters need to be adjusted. If it is found that some parameters deviate from the optimal range, a suggestion is sent to the control center, and the control center automatically or prompts the operator to manually adjust the relevant parameters, and the parameters are adjusted as needed (including adjusting temperature, pressure, aqueous phase volume, oil phase volume, etc.).

[0066] S7. When an abnormal situation is detected, the alarm module issues an alarm in a timely manner.

[0067] S8. After the preliminary emulsification is completed, the suction pump is started to transport the material in the rotating drum to the high-pressure homogenizer for homogenization treatment. The high-pressure homogenizer further processes the material, ensuring the quality of the nanoparticle drug carrier. The material after being processed by the high-pressure homogenizer is the required nanoparticle drug carrier.

[0068] 3. Beneficial effects

[0069] One or more technical solutions provided in the technical solution of the present application have at least the following technical effects or advantages.

[0070] 1. In the present invention, the emulsification mechanism and the rotating drum are driven by a motor to rotate in the reverse direction for preliminary emulsification, and then the rotation drive is used to drive the stirring shaft to rotate synchronously, and the cavitation effect of the ultrasonic generator are combined in multiple ways to greatly improve the emulsification and stirring effect, so that the material can be fully emulsified and dispersed, ensuring the uniformity of the nanoparticle drug carrier.

[0071] 2. Comprehensive monitoring can be realized. The temperature monitoring module, pressure monitoring module, particle size analyzer and liquid level monitoring module are used to monitor the temperature of the emulsion, pressure, nanoparticle particle size and liquid level height in the rotating drum in real time, providing comprehensive data support for the preparation process to detect potential problems in a timely manner.

[0072] 3. The comprehensive analysis and evaluation module integrates various information and combines historical data to comprehensively evaluate the preparation process and predict risks, and adjusts the preparation parameters according to the evaluation results to ensure that the preparation process is always in the best state, improve product quality and reduce the defective rate.

[0073] 4. The preliminarily emulsified material is transported to a high-pressure homogenizer by a suction pump for homogenization treatment, further ensuring the quality of the nanoparticle drug carrier and meeting the production requirements.

[0074] 5. When the dialing block passes through the material, it will disrupt the original laminar flow state of the material, causing the material to generate strong turbulence. Turbulence can increase the collision and mixing opportunities between different components in the material, promoting the dispersion and emulsification of the oil phase and the water phase. It promotes the cyclic flow of the material, further facilitating the emulsification process. The scraper of the wall scraping assembly can scrape off the material adhering to the inner wall of the rotating cylinder. This enables the material to be more evenly mixed and dispersed within the rotating cylinder, ensuring the uniformity of the emulsification effect. This helps to prepare a nanoparticle drug carrier with more uniform particle size and more stable quality. The dialing block on the inner wall of the rotating cylinder can enhance the degree of turbulence and cyclic flow of the material, and the material scraped off by the wall scraping assembly can quickly mix with other materials in the rotating cylinder under the action of the dialing block, further improving the emulsification effect. Description of the Drawings

[0075] Figure 1 It is an overall schematic diagram of a nanoparticle drug carrier preparation device disclosed in a preferred embodiment of the present application.

[0076] Figure 2 It is an internal structure schematic diagram of a nanoparticle drug carrier preparation device disclosed in a preferred embodiment of the present application.

[0077] Figure 3 is Figure 2 the sectional view taken along the line A-A in

[0078] Figure 4 It is a schematic diagram of the emulsification mechanism of a nanoparticle drug carrier preparation device disclosed in a preferred embodiment of the present application.

[0079] Figure 5 It is a schematic diagram of the rotational drive of a nanoparticle drug carrier preparation device disclosed in a preferred embodiment of the present application.

[0080] Reference Numerals: 1, emulsification barrel; 2, barrel cover; 3, rotating cylinder; 4, emulsification mechanism; 5, wall scraping assembly; 6, rotational drive; 7, drive gear; 8, transmission gear; 9, motor A; 10, ultrasonic probe; 11, water storage tank; 12, drug storage tank; 13, solvent storage tank; 14, emulsification pump; 15, high-pressure homogenizer; 16, suction pump; 17, oil storage tank; 18, oil pump; 31, dialing block; 32, toothed ring; 41, rotating seat; 42, stirring shaft; 43, stirring blade; 44, bevel gear A; 51, rotating plate; 52, slider; 53, scraper; 61, motor B; 62, driving gear; 63, shaft rod; 64, driven gear; 65, bevel gear B. Detailed Embodiments

[0081] The present application is further described in detail below in conjunction with the accompanying drawings.

[0082] Reference Figure 1 , Figure 2 and Figure 3 The embodiment of the present application provides a device for preparing a nanoparticle drug carrier, including an emulsifying barrel 1, a barrel cover 2, a rotating drum 3, an emulsifying mechanism 4, a wall scraping assembly 5, a driving gear 7, a transmission gear 8, a motor A9, an ultrasonic probe 10, a high-pressure homogenizer 15, a suction pump 16 and a monitoring mechanism.

[0083] A rotating drum 3 is rotatably arranged in the emulsifying barrel 1 ; a motor is fixedly arranged at the bottom of the emulsifying barrel 1 , and the output shaft of the motor extends into the emulsifying barrel 1 , and the output shaft of the motor is detachably fixedly connected to the emulsifying mechanism 4 .

[0084] A transmission gear 8 is rotatably provided at the bottom of the emulsifying barrel 1; a driving gear 7 is coaxially fixedly provided on the output shaft of the motor, and a gear ring 32 is fixedly provided at the bottom of the rotating drum 3; the transmission gear 8 is meshed and connected with the driving gear 7 and the gear ring 32 respectively. The motor can drive the rotating drum 3 to rotate through the transmission gear 8, the driving gear 7 and the gear ring 32, and the rotating direction of the rotating drum 3 is opposite to that of the emulsifying mechanism 4. The function of the rotating drum 3 is to contain the material to be emulsified, and to work in conjunction with the emulsifying mechanism 4 during the rotation process to promote the full mixing and emulsification of the material.

[0085] A wall scraping assembly 5 is detachably fixedly provided on the emulsifying mechanism 4 .

[0086] The barrel cover 2 and the drum 3 are sealed and rotatably connected; the barrel cover 2 is detachably fixedly provided on the upper end of the emulsification barrel 1; an ultrasonic probe 10 is provided on the barrel cover 2, and the ultrasonic probe 10 is connected to the ultrasonic generator. When the ultrasonic generator is started, the ultrasonic probe 10 converts the electrical signal into high-frequency mechanical vibration, and transmits the vibration to the material in the drum 3. The ultrasonic wave produces a cavitation effect in the material, that is, tiny bubbles are formed and quickly collapsed, generating a strong impact force and a local high temperature and high pressure environment. This cavitation effect can further break up the particles in the material, promote the dispersion and mixing of droplets, improve the effect and efficiency of emulsification, and make the prepared nanoparticle drug carrier more uniform in particle size and better in stability.

[0087] A suction pump 16 is fixedly arranged on the high-pressure homogenizer 15, and an input end of the suction pump 16 is arranged on the barrel cover 2. The input end of the suction pump 16 passes through the barrel cover 2 and can extend into the bottom of the drum 3. The high-pressure homogenizer 15 is used to further homogenize the material after preliminary emulsification to reduce the particle size of the nanoparticles and make their distribution more uniform.

[0088] A monitoring mechanism is fixedly arranged on the barrel cover 2; the monitoring mechanism monitors and regulates the preparation process of the nanoparticle drug carrier.

[0089] In this technical solution, the materials for preparing the nanoparticle drug carrier are added into the rotating drum 3. The barrel cover 2 is covered, the motor is started, the motor drives the emulsifying mechanism 4 to rotate, and at the same time, by driving the rotating drum 3 to rotate in the reverse direction, the preliminary emulsification of the materials is started. The ultrasonic generator is started, and the ultrasonic probe 10 emits ultrasonic waves into the materials, and the cavitation effect is used to further promote the emulsification and dispersion of the materials. During the emulsification process, the scraping wall assembly 5 continuously scrapes off the materials on the inner wall of the rotating drum 3 to ensure the full mixing of the materials. The monitoring mechanism monitors various parameters in the preparation process in real time and adjusts them as needed. When the preliminary emulsification is completed, the suction pump 16 is started to transport the materials in the rotating drum 3 to the high-pressure homogenizer 15 for homogenization treatment. The materials processed by the high-pressure homogenizer 15 are the required nanoparticle drug carrier. The rotating drum 3 and the emulsifying mechanism 4 rotating in the reverse direction improve the emulsification efficiency and quality of the materials. The scraping wall assembly 5 ensures the full utilization of the materials and the uniformity of emulsification. The application of the ultrasonic probe 10 further enhances the emulsification effect, making the nanoparticle particle size more uniform. The high-pressure homogenizer 15 further processes the materials to ensure the quality of the nanoparticle drug carrier. The real-time monitoring and adjustment function of the monitoring mechanism ensure the stability of the preparation process and the consistency of the product quality.

[0090] Further, a plurality of emulsifying pumps 14 are connected and arranged on the barrel cover 2 through hoses; flow control valves are arranged on the hoses.

[0091] The input ends of the emulsifying pumps 14 all extend into the water storage tank 11, the drug storage tank 12 and the solvent storage tank 13. Water, drugs and solvents are stored in the water storage tank 11, the drug storage tank 12 and the solvent storage tank 13 respectively. By adjusting the opening degree of the flow control valve, the delivery flow rates of water, drug raw materials and solvents are accurately controlled.

[0092] An oil storage tank 17 is connected and arranged on the barrel cover 2 through a hose. An oil pump 18 is fixedly arranged on the oil storage tank 17, and the input end of the oil pump 18 extends to the bottom of the oil storage tank 17. An oil phase is stored in the oil storage tank 17. A suitable oil phase is selected according to the properties of the drug such as solubility, stability and pharmacological activity.

[0093] Further, a plurality of dial blocks 31 are evenly arranged on the inner wall of the rotating drum 3 to improve the emulsification effect. The shape of the dial block 31 can be rectangular, trapezoidal, triangular, etc. Different-shaped dial blocks will produce different hydrodynamic effects when stirring the materials. The material of the dial block 31 is stainless steel.

[0094] In this technical solution, when the shifting block passes through the material, it will disrupt the original laminar flow state of the material, causing strong turbulence in the material. Turbulence can increase the collision and mixing opportunities between different components in the material, promoting the dispersion and emulsification of the oil phase and the water phase. To promote the circulating flow of the material, the shifting block 31 can also drive the material to circulate within the rotating drum 3. When the rotating drum rotates, the shifting block will push the material near the inner wall towards the center of the rotating drum, while driving the material in the central area towards the outer wall, forming a circulating flow pattern. This circulating flow enables the material to come into full contact with the emulsifying mechanism 4 and other additives, further promoting the emulsification process. For example, components such as drugs, oil phase, water phase, and emulsifiers can be more evenly mixed during the circulating flow, contributing to the formation of a stable nanoparticle drug carrier. To increase the shear force, the shifting block 31 generates a shear force on the material during rotation. Shear force is an important force for breaking oil droplets and water droplets, and it can divide larger droplets into smaller droplets. The magnitude and distribution of the shear force generated by shifting blocks of different shapes and sizes also vary.

[0095] Referring to Figure 4 , the emulsifying mechanism 4 includes a rotating base 41, a stirring shaft 42, stirring blades 43, and a rotation drive 6.

[0096] The rotating base 41 is detachably and fixedly arranged on the output shaft of the motor; two stirring shafts 42 are rotatably arranged on the rotating base 41; a number of stirring blades 43 are arranged on the stirring shafts 42 in a staggered manner.

[0097] A rotation drive 6 is fixedly arranged on the rotating base 41; the rotation drive 6 is in transmission connection with the stirring shaft 42.

[0098] In this technical solution, while the motor drives the rotating base 41 and the stirring shaft 42 to revolve, the rotation drive 6 drives the two stirring shafts 42 to rotate on their own axes, and the stirring shaft 42 drives the stirring blades 43 to rotate, improving the emulsification uniformity effect.

[0099] Referring to Figure 5 , the rotation drive 6 includes a motor B 61, a driving gear 62, a shaft rod 63, a driven gear 64, and a bevel gear B 65.

[0100] A motor B 61 is fixedly arranged on the rotating base 41; the output end of the motor B 61 is coaxially and fixedly provided with a driving gear 62; a shaft rod 63 is rotatably arranged on the rotating base 41, and a driven gear 64 is coaxially and fixedly arranged on the shaft rod 63; the driven gear 64 is in meshing transmission connection with the driving gear 62.

[0101] Bevel gears B 65 are coaxially and fixedly arranged at both ends of the shaft rod 63, and a bevel gear A 44 is coaxially and fixedly arranged on the stirring shaft 42; the bevel gear A 44 is in meshing transmission connection with the bevel gear B 65.

[0102] In this technical solution, the starting motor B61 drives the driving gear 62 to rotate. The driving gear 62 drives the driven gear 64 and the shaft rod 63 to rotate. The shaft rod 63 drives the bevel gear B65 to rotate. The bevel gear B65 drives the bevel gear A44 to rotate, thereby driving the two stirring shafts 42 to rotate synchronously, improving the emulsification and stirring effect.

[0103] Referring to Figure 2 , the scraping wall assembly 5 includes a rotating plate 51, a slider 52 and a scraping plate 53.

[0104] The rotating plate 51 is detachably and fixedly arranged on the rotating seat 41 of the emulsifying mechanism 4; sliders 52 are slidably arranged at both ends of the rotating plate 51; a spring is arranged between the slider 52 and the rotating plate 51; the other end of the slider 52 is fixedly provided with a scraping plate 53, and the scraping plate 53 is in frictional contact with the inner wall of the rotating cylinder 3.

[0105] In this technical solution, the scraping plate 53 can scrape off the materials adhering to the inner wall of the rotating cylinder 3. When encountering uneven places of the dial block 31 on the inner wall of the rotating cylinder 3, the slider 52 will automatically adjust its position under the action of the spring. At the same time, the elastic action of the spring can also buffer the frictional force between the scraping plate 53 and the inner wall of the rotating cylinder 3, reduce the wear of the scraping plate 53 and the inner wall of the rotating cylinder 3, and extend its service life. The materials adhering to the inner wall of the rotating cylinder 3 may form local accumulations, resulting in uneven material distribution and thus affecting the emulsification effect. The scraping wall assembly 5 continuously scrapes off the materials on the inner wall, enabling the materials to be more evenly mixed and dispersed in the rotating cylinder 3, ensuring the uniformity of the emulsification effect. This helps to prepare nanoparticle drug carriers with more uniform particle sizes and more stable quality. The dial block 31 on the inner wall of the rotating cylinder 3 can enhance the turbulence degree and circulating flow of the materials, and the materials scraped off by the scraping wall assembly 5 can be quickly mixed with other materials in the rotating cylinder under the action of the dial block 31. This synergistic effect makes the mixing of the materials in the rotating cylinder 3 more sufficient, further improving the emulsification effect. At the same time, the scraping wall assembly 5 keeps the inner wall of the rotating cylinder 3 clean, which is also beneficial for the dial block 31 to better play its role and avoid the accumulation of materials from hindering the movement of the dial block 31.

[0106] Furthermore, a heating plate is fixedly arranged at the bottom inside the rotating cylinder 3, and a temperature sensor is fixedly arranged on the rotating cylinder 3.

[0107] Furthermore, a concentration sensor, a liquid level sensor, a pressure sensor and a particle size analyzer are arranged on the barrel cover 2.

[0108] Furthermore, a pressure regulating device is connected to the barrel cover 2. The pressure regulating device includes:

[0109] Air compressor: Compresses air through mechanical movement, increases the air pressure, and provides the initial high-pressure air source for the entire pressure regulating system.

[0110] Air storage tank: Used to store the high-pressure air compressed by the air compressor. When the air pressure output by the air compressor is unstable, the air storage tank can store the excess air and release it when needed to ensure the relative stability of the system air pressure.

[0111] Pneumatic pressure regulating valve: The pneumatic pressure regulating valve controls the gas flow by adjusting the opening of the valve, thereby achieving the regulation of air pressure.

[0112] Air filter: The air filter removes pollutants such as dust, impurities, and oil droplets in the compressed air through filtering media (such as filter screens, filter elements, etc.). Different types of filters have different filtration precisions, and the appropriate filter can be selected according to actual needs. Application scenario: Installed after the air source equipment to ensure the cleanliness of the gas entering the pressure regulation system and the preparation equipment, prevent pollutants from having an adverse impact on the nanoparticle preparation process, and ensure the drug quality.

[0113] Dryer: The dryer is used to remove the moisture in the compressed air. The common drying methods are adsorption drying and refrigeration drying. In the preparation of nanoparticle drug carriers, moisture may affect the stability of the drug and the formation of nanoparticles. Therefore, the dryer can ensure the dryness of the gas entering the system and improve the reliability of the preparation process.

[0114] Safety valve: The safety valve is a safety protection device. When the air pressure in the system exceeds the set safety value, the safety valve will automatically open, release some gas, reduce the air pressure, and prevent the equipment from being damaged due to overpressure. Common safety valves include spring type, pilot type, etc.

[0115] Furthermore, the monitoring mechanism includes:

[0116] Data collection module: Collects a large amount of data on the materials, temperature, pressure, concentration, etc. in the preparation of nanoparticle drug carriers. Widely collects various key data involved in the nanoparticle drug preparation process. In terms of materials, record the specific types, specifications, and batch information of the aqueous phase, oil phase, solvent, and drug, because materials with different sources and properties may have a significant impact on the preparation results. Temperature data can reflect the thermal environment during the preparation process, pressure data is related to the mixing and homogenization degree of the materials, and concentration data involves the content of drugs, carrier materials, etc. in the system. These are all important factors determining the quality of nanoparticles. Label the collected data to facilitate subsequent analysis and processing. The labeling content includes information such as the data collection time, collection location, and related operation steps. When labeling temperature data, also record whether the temperature is collected during the emulsification start stage, homogenization process, or cooling stage, which helps analyze the influence of temperature at different stages on nanoparticle formation.

[0117] Temperature monitoring module: Includes a temperature sensor to real-time monitor the temperature of the emulsion in the rotating drum 3.

[0118] Pressure monitoring module: It includes a pressure sensor to monitor the pressure inside the rotating drum 3 in real time.

[0119] Particle size analyzer: To monitor the particle size of the nanoparticles.

[0120] Liquid level monitoring module: It includes a liquid level sensor to monitor the liquid level height inside the rotating drum 3 in real time.

[0121] Comprehensive analysis and evaluation module: It fuses information such as aqueous phase, oil phase, solvent, temperature, pressure, particle size, etc., comprehensively evaluates the preparation process of the rice grain drug carrier, and adjusts the parameters as needed. It can detect abnormal situations in a timely manner. It includes information fusion evaluation and parameter adjustment decision-making.

[0122] Information fusion evaluation: This module fuses and analyzes information such as the types and dosages of the aqueous phase, oil phase, and solvent, as well as temperature, pressure, particle size, etc. By establishing mathematical models and data analysis algorithms, it comprehensively evaluates the overall situation of the preparation process of the nanoparticles drug carrier. For example, it analyzes the influence of different material combinations on the particle size and stability of the nanoparticles under specific temperature and pressure conditions, so as to judge whether the preparation process is in the optimal state.

[0123] Parameter adjustment decision-making: According to the comprehensive evaluation results, this module can judge whether it is necessary to adjust the preparation parameters. If it is found that some parameters deviate from the optimal range, it will send a suggestion to the control center, and the control center will automatically or prompt the operator to manually adjust the relevant parameters, such as adjusting the flow control valve to change the feeding ratio of the materials, and adjusting the heating or cooling equipment to control the temperature, etc. At the same time, this module can also detect abnormal situations in the preparation process in a timely manner, such as sudden increase in particle size, abnormal temperature fluctuations, etc., and feedback the abnormal information to the control center.

[0124] Alarm module: It includes an alarm. When an abnormal situation is detected, it will send an alarm in a timely manner.

[0125] Control center: It is network-connected to the data collection module, temperature monitoring module, flow control valve, pressure monitoring module, particle size analyzer, liquid level monitoring module, and comprehensive analysis and evaluation module. It receives a large amount of data from each module and centrally processes and analyzes these data. Through built-in algorithms and programs, the control center can quickly judge the rationality of the data and the status of the preparation process. Instruction issuance and regulation. According to the data analysis results, the control center can automatically issue instructions to regulate each module and equipment. For example, when the temperature monitoring module feedbacks that the temperature is too high, the control center will send an instruction to reduce the power of the heating equipment; when the particle size analyzer shows that the particle size of the nanoparticles is too large, the control center will adjust the stirring speed of the emulsifying mechanism or the pressure of the high-pressure homogenizer. At the same time, the control center can also interact with the operator, provide operation suggestions and prompts, and realize the intelligent control of the preparation process of the nanoparticles drug carrier.

[0126] Furthermore, the comprehensive analysis and evaluation module: integrates information such as the aqueous phase, oil phase, solvent, temperature, pressure, particle size, etc., comprehensively evaluates the preparation process of the rice grain drug carrier, adjusts the parameters as needed, and promptly detects abnormal situations. It includes the following steps:

[0127] 1. Data preprocessing: Obtain information on the types and dosages of the aqueous phase, oil phase, and solvent from the data collection module, as well as temperature data from the temperature monitoring module, pressure data from the pressure monitoring module, particle size data from the particle size analyzer, etc. Ensure the accuracy and integrity of the data, and mark the missing or abnormal data. Perform data cleaning to remove duplicate, incorrect, or invalid data, and standardize the collected data so that different types of data are comparable. For example, convert data such as temperature and pressure to a unified unit and range. Perform data integration to integrate the processed data according to the time series or preparation batch to form a complete data set for subsequent analysis.

[0128] 2. Establish a mathematical model: Select a multiple linear regression model according to the characteristics and requirements of nanoparticle drug carrier preparation. Use historical data to train the selected model and determine the model parameters. By continuously adjusting the model parameters, make the model accurately reflect the relationship between various factors in the preparation process.

[0129] The model is: D = β0 + β1W + β2O + β3S + β4T + β5P + E; where D is the particle size of the nanoparticles. This is the target variable to be predicted and analyzed by the entire model. In the preparation of nanoparticle drug carriers, the particle size of the nanoparticles is a very critical indicator, which directly affects the release rate, bioavailability, targeting and distribution of the drug in the body. W is the amount of water phase. In the preparation of nanoparticles, the water phase is usually used as a continuous phase to provide a dispersion medium for other components. O is the amount of oil phase. The oil phase is often used as a carrier of the drug or the core component of the nanoparticles in the preparation of nanoparticles. Changes in the amount of oil phase will affect the structure and size of the nanoparticles. If the amount of oil phase is too much, larger oil droplets may be formed, and the particle size of the nanoparticles prepared in the end will also be larger; conversely, if the amount of oil phase is too little, it may not be able to effectively encapsulate the drug or form a stable nanoparticle structure. S is the amount of solvent. The role of the solvent is to dissolve the drug, carrier material and other components so that they can be evenly dispersed in the system. Different amounts of solvent will affect the viscosity, solubility and intermolecular interactions of the system, thus affecting the particle size of the nanoparticles. For example, insufficient amounts of solvent may lead to incomplete dissolution of some components, affecting the uniformity and particle size of the nanoparticles; while excessive amounts of solvent may increase the difficulty of subsequent separation and removal of the solvent, and may also affect the stability of the nanoparticles. T is temperature. Temperature is one of the important physical factors affecting the preparation process of nanoparticles. Under different temperature conditions, the thermal motion rate of molecules, the chemical reaction rate and the solubility of substances will change. Higher temperatures may accelerate the movement of molecules and promote the emulsification and dispersion process, but may also cause drug decomposition or carrier material denaturation; lower temperatures may increase the viscosity of the system, which is not conducive to the formation and uniform dispersion of nanoparticles. Therefore, temperature has a significant effect on the particle size of nanoparticles. P is pressure. Pressure also plays an important role in the preparation of nanoparticles, especially in some processes involving high-pressure homogenization. Appropriate pressure can make the oil phase and the water phase mix better, break up larger particles, and thus prepare nanoparticles with smaller and more uniform particle sizes. Too high a pressure may cause equipment damage or excessive crushing of nanoparticles; too low a pressure may fail to achieve the desired homogenization effect, resulting in a larger nanoparticle size. β0 is the intercept term. Β1, β2, β3, β4, and β5 are the regression coefficients of water phase dosage, oil phase dosage, solvent dosage, temperature, and pressure, respectively. The regression coefficient represents the average change in the dependent variable (nanoparticle size) for each unit change in the independent variable when other independent variables remain unchanged. E is the error term.

[0130] Model validation: Use a portion of data that was not used in training to validate the established model and evaluate the accuracy and reliability of the model. If the model's prediction results deviate greatly from the actual situation, the model needs to be adjusted and optimized.

[0131] 3. Data analysis:

[0132] Feature extraction: Extract features related to the nanoparticle preparation process from the integrated dataset, such as the proportions of different material combinations, the changing trends of temperature and pressure, the distribution characteristics of particle size, etc. These features will be used as the input of the model for analyzing and evaluating the preparation process.

[0133] Model calculation: Input the extracted features into the established mathematical model for calculation and analysis. The model will predict key indicators such as the particle size and stability of the nanoparticles based on the input features and compare them with the preset target values.

[0134] 4. Comprehensive evaluation: According to the calculation results of the model, comprehensively consider factors such as the aqueous phase, oil phase, solvent, temperature, pressure, and particle size, and evaluate the overall situation of the nanoparticle drug carrier preparation process. Determine whether the preparation process is in the optimal state. Combine historical data to predict whether there are potential problems or risks. The risk prediction is carried out according to the following formula:

[0135] R = Σ n i＝1 (w ti * d i * r i ); w ti = w i / [H i * Σ n i＝1 (w k / H k )]; d i = | x i - x i0 | / x io .

[0136] H i =- Σ m j-1 [pij * log2(p ij )]; In the formula, R is the risk assessment coefficient, which is a key indicator calculated by integrating various factors and is used to measure the risk degree of the nanoparticle drug carrier preparation process. By comparing with the risk threshold, it is judged whether there are potential risks in the preparation process. x i represents the i-th factor affecting the nanoparticle drug carrier preparation, including the aqueous phase, oil phase, solvent, temperature, pressure, and particle size, etc. The value range of i is from 1 to n, and n is the total number of influencing factors. x io is the standard value of the i-th factor and is used to calculate the deviation degree of the actual value of the factor from the standard value. d i is the deviation degree of the actual value of the i-th factor from the standard value, reflecting the difference between the current state and the standard state of this factor. H iis the information entropy of the i-th factor, which is used to measure the uncertainty of the data of this factor. Where m is the number of states of this factor in historical data, and p ij is the probability that the i-th factor is in the j-th state. The larger the information entropy, the higher the data uncertainty of this factor. w i is the initially set weight of the i-th factor, which reflects the relative importance of each factor's influence on the preparation process and can be determined by methods such as the analytic hierarchy process. w ti is the dynamic weight of the i-th factor adjusted based on information entropy. r i is the risk correlation factor, and its value range is 0 - 1. By statistically analyzing historical data, the variation law of each factor when a risk event occurs is calculated. r i The closer it is to 1, the stronger the correlation between this factor and the risk event. R0 is the risk threshold, which is a preset standard value. When the risk assessment coefficient, it is judged that there are potential risks in the preparation process; when, it is considered that the preparation process is in a relatively safe state. w k is the initially set weight of the k-th factor. H k is the information entropy of the i-th factor.

[0137] 5. Parameter adjustment decision:

[0138] 5.1. Judge the deviation of parameters: According to the process requirements and quality standards of nanoparticle drug carrier preparation, reasonable threshold ranges are set for each parameter. Compare the parameter values calculated by the model with the set threshold ranges to judge whether there are parameter deviations. If a certain parameter exceeds the threshold range, it is considered that this parameter is abnormal.

[0139] For the parameters that deviate from the threshold range, further evaluate their degree of abnormality. Make a comprehensive evaluation according to factors such as the deviation amplitude and duration to judge the severity of the abnormal situation.

[0140] 5.2. Generate adjustment suggestions: When parameter deviations are found, use the established mathematical model and data analysis algorithm to analyze the reasons for the parameter deviations. For example, if the particle size suddenly increases, it may be caused by reasons such as too high temperature, unstable pressure, or imbalance of material ratio.

[0141] Formulate adjustment strategies. According to the results of the cause analysis, formulate corresponding parameter adjustment strategies. For example, if the particle size increases due to too high temperature, it can be recommended to reduce the power of the heating equipment; if the material ratio is out of balance, it can be recommended to adjust the flow control valve to change the feeding ratio.

[0142] Convert the formulated adjustment strategies into specific adjustment suggestions, including the name of the parameter to be adjusted, the adjustment direction (increase or decrease), and the adjustment amplitude, etc.

[0143] 5.3. Feedback Execution: Send the generated adjustment suggestions to the control center, and at the same time, also feedback the abnormal situations and relevant data found during the preparation process to the control center. Based on the received adjustment suggestions, the control center selects to automatically or prompt the operator to manually adjust the relevant parameters. If automatic adjustment is selected, the control center will automatically control the corresponding equipment (such as flow control valves, heating or cooling equipment, etc.) according to the suggestions for parameter adjustment; if manual adjustment is selected, the control center will prompt the operator to operate according to the suggestions and provide necessary operation guidance. After the parameter adjustment, continuously monitor various parameters of the preparation process and the quality indicators of the nanoparticles, and evaluate the effect of the adjustment. If the parameters still deviate or do not achieve the expected effect after adjustment, re-analysis and adjustment are required until the preparation process returns to the optimal state.

[0144] The present invention provides a method for using a nanoparticle drug carrier preparation device, comprising the following steps:

[0145] S1. Add the materials for preparing the nanoparticle drug carrier into the rotating drum 3. Cover the drum lid 2, and the heating plate at the bottom inside the rotating drum 3 heats the materials to a predetermined temperature. Start the motor, and the motor drives the emulsifying mechanism 4 to rotate, and at the same time drives the rotating drum 3 to rotate in the reverse direction, and start to preliminarily emulsify the materials.

[0146] S2. The motor B61 of the rotation drive 6 drives the driving gear 62 to rotate, the driving gear 62 drives the driven gear 64 and the shaft rod 63 to rotate, the shaft rod 63 drives the bevel gear B65 to rotate, and the bevel gear B65 drives the bevel gear A44 to rotate, thereby driving the two stirring shafts 42 to rotate synchronously, improving the emulsifying and stirring effect.

[0147] S3. Start the ultrasonic generator, and the ultrasonic probe 10 emits ultrasonic waves into the materials, and further promotes the emulsification and dispersion of the materials by using the cavitation effect. During the emulsification process, the scraping wall assembly 5 continuously scrapes off the materials on the inner wall of the rotating drum 3 to ensure the full mixing of the materials.

[0148] S4. The temperature monitoring module monitors the temperature of the emulsion in the rotating drum 3 in real time; the pressure monitoring module monitors the pressure in the rotating drum 3 in real time; the particle size analyzer monitors the particle size of the nanoparticles; the liquid level monitoring module monitors the liquid level height in the rotating drum 3 in real time.

[0149] S5. The comprehensive analysis and evaluation module of the monitoring mechanism integrates information such as the aqueous phase, oil phase, solvent, temperature, pressure, particle size, etc., comprehensively evaluates the preparation process of the rice grain drug carrier, and combines historical data to predict whether there are potential problems or risks. Detect abnormal situations in a timely manner.

[0150] S6. Determine whether it is necessary to adjust the preparation parameters according to the comprehensive evaluation results. If it is found that some parameters deviate from the optimal range, send a suggestion to the control center, and the control center automatically or prompts the operator to manually adjust the relevant parameters, and adjust the parameters as needed (including adjusting the temperature, pressure, amount of aqueous phase, amount of oil phase, etc.).

[0151] S7. When an abnormal situation is monitored, the alarm module issues an alarm in a timely manner.

[0152] S8. After the initial emulsification is completed, start the suction pump 16 to transport the material in the rotating drum 3 to the high-pressure homogenizer 15 for homogenization treatment. The high-pressure homogenizer 15 further processes the material to ensure the quality of the nanoparticle drug carrier. The material after being processed by the high-pressure homogenizer 15 is the required nanoparticle drug carrier.

[0153] The working principle of the nanoparticle drug carrier preparation device of the present invention is as follows: Add the material for preparing the nanoparticle drug carrier into the rotating drum 3. Cover the barrel cover 2, and the heating plate at the bottom inside the rotating drum 3 heats the material to a predetermined temperature. Start the motor, the motor drives the emulsification mechanism 4 to rotate, and at the same time drives the rotating drum 3 to rotate in the opposite direction to start the initial emulsification of the material. The motor B61 of the rotation drive 6 drives the driving gear 62 to rotate, the driving gear 62 drives the driven gear 64 and the shaft rod 63 to rotate, the shaft rod 63 drives the bevel gear B65 to rotate, and the bevel gear B65 drives the bevel gear A44 to rotate, thereby driving the two stirring shafts 42 to rotate synchronously to improve the emulsification and stirring effect. Start the ultrasonic generator, and the ultrasonic probe 10 emits ultrasonic waves into the material to further promote the emulsification and dispersion of the material by using the cavitation effect. During the emulsification process, the scraping wall assembly 5 continuously scrapes off the material on the inner wall of the rotating drum 3 to ensure the full mixing of the material. The temperature monitoring module monitors the temperature of the emulsion in the rotating drum 3 in real time; the pressure monitoring module monitors the pressure in the rotating drum 3 in real time; the particle size analyzer monitors the particle size of the nanoparticles; the liquid level monitoring module monitors the liquid level height in the rotating drum 3 in real time; the comprehensive analysis and evaluation module of the monitoring mechanism integrates information such as the aqueous phase, oil phase, solvent, temperature, pressure, and particle size, conducts a comprehensive evaluation of the process of preparing the rice grain drug carrier, combines historical data, predicts whether there are potential problems or risks, and discovers abnormal situations in a timely manner. Determine whether it is necessary to adjust the preparation parameters according to the comprehensive evaluation results, and adjust the parameters as needed. When an abnormal situation is monitored, the alarm module issues an alarm in a timely manner. After the initial emulsification is completed, start the suction pump 16 to transport the material in the rotating drum 3 to the high-pressure homogenizer 15 for homogenization treatment. The high-pressure homogenizer 15 further processes the material to ensure the quality of the nanoparticle drug carrier. The material after being processed by the high-pressure homogenizer 15 is the required nanoparticle drug carrier.

[0154] In the present invention, the emulsifying mechanism and the rotating drum are driven by a motor to rotate in opposite directions for preliminary emulsification. Then, the rotating drive is used to drive the stirring shaft to rotate synchronously, and the cavitation effect of the ultrasonic generator is utilized. The combination of multiple methods greatly improves the emulsification and stirring effect, enabling the material to be fully emulsified and dispersed, and ensuring the uniformity of the nanoparticle drug carrier. Comprehensive monitoring can be achieved. By using the temperature monitoring module, pressure monitoring module, particle size analyzer, and liquid level monitoring module, the temperature, pressure, nanoparticle size, and liquid level height of the emulsion in the rotating drum are monitored in real time, providing comprehensive data support for the preparation process to promptly discover potential problems. The comprehensive analysis and evaluation module integrates various information and combines historical data to comprehensively evaluate and predict risks for the preparation process, and adjusts the preparation parameters according to the evaluation results to ensure that the preparation process is always in the best state, improving product quality and reducing the defective rate. The material after preliminary emulsification is transported to a high-pressure homogenizer by a suction pump for homogenization treatment, further ensuring the quality of the nanoparticle drug carrier and meeting the production requirements.

[0155] As described above, the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: they can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for using a nanoparticle drug carrier preparation device, characterized in that: The following steps are involved: S1. Add the material of the nanoparticle drug carrier to be prepared into the drum, heat the material through the heating plate, and drive the emulsification mechanism to rotate by the motor, and at the same time drive the drum to rotate in the opposite direction to preliminarily emulsify the material; S2, the rotation drive drives the two stirring shafts and stirring blades to rotate, thereby improving the emulsification stirring effect; S3, start the ultrasonic generator, the ultrasonic probe emits ultrasonic waves into the material, and uses the cavitation effect to further promote the emulsification and dispersion of the material; the scraping component continuously scrapes the material on the inner wall of the drum to ensure that the material is fully mixed; S4, the temperature monitoring module monitors the temperature of the emulsion in the drum in real time; the pressure monitoring module monitors the pressure in the drum in real time; the particle size analyzer monitors the particle size of the nanoparticles; S5. The comprehensive analysis and evaluation module of the monitoring agency integrates multi-source information to conduct a comprehensive evaluation of the rice grain drug carrier preparation process, predict potential problems or risks, and detect abnormal situations in a timely manner; S6. Determine whether the preparation parameters need to be adjusted based on the comprehensive evaluation results; adjust the parameters as needed; S7. When an abnormal situation is detected, the alarm module will issue an alarm in time; S8. After the initial emulsification is completed, start the suction pump to transport the material in the drum to the high-pressure homogenizer for homogenization to obtain nanoparticle drug carriers.

2. The method for using the nanoparticle drug carrier preparation device according to claim 1, characterized in that: Step S5 includes the following steps: S51, data preprocessing: obtaining the type and amount information of the water phase, oil phase, and solvent, as well as the temperature data of the temperature monitoring module, the pressure data of the pressure monitoring module, and the particle size data of the particle size analyzer; performing data cleaning, standardizing the collected data, and performing data integration; S52. Establishing a mathematical model: selecting a multiple linear regression model, using historical data to train the selected model, determining the parameters of the model, and continuously adjusting the model parameters so that the model can accurately reflect the relationship between various factors in the preparation process; verifying and optimizing the established model; S53, data analysis: extract the features related to the nanoparticle preparation process from the integrated data set, input the extracted features into the established mathematical model for calculation and analysis. The model will predict the particle size and key stability indicators of the nanoparticles based on the input features and compare them with the preset target values; S54. Comprehensive evaluation: Based on the calculation results of the model, the overall situation of the nanoparticle drug carrier preparation process is evaluated to predict potential problems or risks; S55, parameter adjustment decision: S55.

1. Determine parameter deviation: Compare the parameter values ​​calculated by the model with the set threshold range to determine whether there is parameter deviation; for parameters that deviate from the threshold range, further evaluate their degree of abnormality; conduct a comprehensive evaluation based on the magnitude and duration of the deviation; S55.

2. Generate adjustment suggestions: When parameter deviation is found, use the established mathematical model and data analysis algorithm to analyze the cause of the parameter deviation, and formulate corresponding parameter adjustment strategies based on the results of the cause analysis; S55.

3. Feedback execution: The generated adjustment suggestions are sent to the control center, and the control center adjusts the relevant parameters according to the received adjustment suggestions.

3. The method for using the nanoparticle drug carrier preparation device according to claim 2, characterized in that: In step S52, the model is: D = β0 + β1W + β2O + β3S + β4T + β5P + E; wherein D is the particle size of the nanoparticles; W is the amount of water phase; O is the amount of oil phase; S is the amount of solvent; T is the temperature; P is the pressure; β0 is the intercept term; β1, β2, β3, β4 and β5 are the regression coefficients of the amount of water phase, the amount of oil phase, the amount of solvent, the temperature and the pressure respectively; E is the error term; In step S54, risk prediction is performed according to the following formula: R=Σ n i＝1 (w ti *d i *r i );w ti =w i / [H i *Σ n i＝1 (w k / H k )];d i =|x i -x i0 | / x io ; H i =-Σ m j-1 [pij*log2(p ij )]; where R is the risk assessment coefficient; x i represents the i-th factor affecting the preparation of nanoparticle drug carriers, i ranges from 1 to n, and n is the total number of influencing factors; x io is the standard value of the ith factor; d i is the degree of deviation between the actual value of the factor and the standard value; H i is the information entropy of the i-th factor; m is the number of states of the factor in the historical data, p ij is the probability that the ith factor is in the ith state; w i is the weight of the th factor initially set; w ti is the dynamic weight of the factor after adjustment based on information entropy; r i is the risk association factor; R0 is the risk threshold; w k is the weight of the kth factor initially set, H k is the information entropy of the th factor.

4. The method for using the nanoparticle drug carrier preparation device according to claim 1, characterized in that: The barrel cover is connected to a plurality of emulsification pumps through a hose; each hose is provided with a flow control valve; the input ends of the emulsification pumps are respectively connected to a water storage tank, a medicine storage tank and a solvent storage tank; The barrel cover is connected to an oil storage tank through a hose, an oil pump is fixedly arranged on the oil storage tank, and an input end of the oil pump extends into the bottom of the oil storage tank; A plurality of shifting blocks are evenly arranged on the inner wall of the rotating drum, and the material of the shifting blocks is stainless steel.

5. The method for using the nanoparticle drug carrier preparation device according to claim 2, characterized in that: The shape of the shifting block is rectangular, trapezoidal or triangular, and shifting blocks of different shapes produce different fluid mechanics effects when stirring materials.

6. The method for using the nanoparticle drug carrier preparation device according to claim 1, characterized in that: The emulsifying mechanism includes a rotating seat, a stirring shaft, stirring blades and a rotating drive; The rotating seat is detachably fixed on the output shaft of the motor; two stirring shafts are rotatably arranged on the rotating seat; a plurality of stirring blades are staggeredly arranged on the stirring shaft; a rotating drive is fixedly arranged on the rotating seat; and the rotating drive is transmission-connected with the stirring shaft.

7. The method for using the nanoparticle drug carrier preparation device according to claim 6, characterized in that: The rotation drive includes a motor B, a driving gear, a shaft, a driven gear and a bevel gear B; A motor B is fixedly arranged on the rotating seat; a driving gear is coaxially fixedly arranged on the output end of motor B; a shaft rod is rotatably arranged on the rotating seat, and a driven gear is coaxially fixedly arranged on the shaft rod; the driven gear is meshed and connected with the driving gear, bevel gears B are coaxially fixedly arranged at both ends of the shaft rod, and a bevel gear A is coaxially fixedly arranged on the stirring shaft; the bevel gear A is meshed and connected with the bevel gear B.

8. The method for using the nanoparticle drug carrier preparation device according to claim 1, characterized in that: The wall scraping assembly includes a rotating plate, a sliding block and a scraper; The rotating plate is detachably fixed on the rotating seat of the emulsifying mechanism; sliders are slidably arranged at both ends of the rotating plate; a spring is arranged between the slider and the rotating plate; a scraper is fixedly arranged at the other end of the slider, and the scraper is arranged in friction contact with the inner wall of the rotating drum; A heating plate is fixedly arranged at the bottom of the rotating drum, and a temperature sensor is fixedly arranged on the rotating drum; a concentration sensor, a liquid level sensor, a pressure regulating device, a pressure sensor and a particle size analyzer are arranged on the barrel cover.

9. The method for using the nanoparticle drug carrier preparation device according to claim 1, characterized in that: Monitoring agencies include: Data collection module: widely collect various key data involved in the preparation process of nanoparticle drug carriers; annotate the collected data; Temperature monitoring module: including temperature sensor, real-time monitoring of the emulsion temperature in the drum; Pressure monitoring module: including pressure sensor, which monitors the pressure in the drum in real time; Particle size analyzer: monitors the particle size of nanoparticles; Liquid level monitoring module: including liquid level sensor, which monitors the liquid level in the drum in real time; Comprehensive analysis and evaluation module: Integrate the information of water phase, oil phase, solvent, temperature, pressure and particle size to comprehensively evaluate the preparation process of rice particle drug carrier and detect abnormal situations in time; Alarm module: including alarm, which will send out alarm in time when abnormal situation is detected; Control center: network connected with data collection module, temperature monitoring module, flow control valve, pressure monitoring module, particle size analyzer, liquid level monitoring module and comprehensive analysis and evaluation module.

10. A device for preparing a nanoparticle drug carrier, comprising: Emulsification barrel, barrel cover, rotating drum, emulsification mechanism, scraping wall assembly, driving gear, transmission gear, motor A, ultrasonic probe, high-pressure homogenizer, suction pump and monitoring mechanism; characterized in that: A rotating drum is rotatably arranged in the emulsification barrel; a motor is fixedly arranged at the bottom of the emulsification barrel, and the output shaft of the motor extends into the emulsification barrel, and the output shaft of the motor is detachably fixedly connected to the emulsification mechanism; A transmission gear is rotatably provided at the bottom of the emulsification barrel; a driving gear is coaxially fixedly provided on the output shaft of the motor, and a gear ring is fixedly provided at the bottom of the rotating drum; the transmission gear is meshed and connected with the driving gear and the gear ring respectively; a scraper assembly is detachably fixedly provided on the emulsification mechanism; a barrel cover is detachably fixedly provided on the upper end of the emulsification barrel; the barrel cover and the rotating drum are sealingly and rotatably connected; an ultrasonic probe is provided on the barrel cover, and the ultrasonic probe is connected to an ultrasonic generator; a suction pump is fixedly provided on the high-pressure homogenizer, and the input end of the suction pump is provided on the barrel cover, and the input end of the suction pump passes through the barrel cover and extends into the bottom of the rotating drum; a monitoring mechanism is fixedly provided on the barrel cover; the monitoring mechanism monitors and regulates the preparation process of the nanoparticle drug carrier.

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