Composite microemulsion preparation containing monosultap and abamectin and preparation process thereof

Abstract

The invention relates to the technical field of pharmacy, and discloses a monosultap and abamectin-containing composite microemulsion preparation and a preparation process thereof, and the process comprises the following steps: optimizing a dissolution rate through a dissolution kinetic model to ensure that active components are fully dissolved and form a uniform mother solution; the pH is stabilized through a PID algorithm, a solubilizer, an emulsifier and an antioxidant are uniformly dispersed to form a water phase system, Taguchi experimental design is adopted to optimize parameters, DLS real-time monitoring is combined to ensure that the particle size of the emulsion is uniformly distributed, the homogenizing pressure is optimized based on a particle size prediction model, the particle size is ensured to be in a stable range through multiple times of homogenizing treatment, and through PID temperature control and filtering resistance monitoring, the particle size of the emulsion is uniformly distributed. Rapidly cooling and removing undissolved particles and impurities, detecting the particle size, the pH value and the component content by using a DLS algorithm, HPLC and GC, sealing and packaging the product, and monitoring the storage temperature and humidity. The preparation provided by the invention has the characteristics of high efficiency, low toxicity and environmental protection, and is suitable for preventing and treating various agricultural pests, and the preparation process is stable and reliable.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceuticals, and in particular relates to a composite microemulsion preparation containing cypermethrin and avermectin and a preparation process thereof. Background Art

[0002] Microemulsion is a homogeneous transparent system composed of oil phase, emulsifier and water phase, which is widely used in the field of pesticides. It has small particle size, high stability and good dispersibility, which can effectively improve the bioavailability of active ingredients and the environmental friendliness of preparations, and has become one of the important directions for the development of pesticide preparations. In the microemulsion system, the active ingredients can be distributed at the nanoscale, thereby enhancing the efficacy and duration of the drug, while reducing the dosage of the drug and the pollution to the environment.

[0003] Abamectin and chlorfenapyr are two widely used insecticides, each with a unique insecticidal mechanism. Abamectin acts on the nervous system of pests, has the dual functions of contact killing and stomach poisoning, and is highly selective against mites and a variety of pests; chlorfenapyr metabolizes to produce nereis toxins, which quickly act on the nerve conduction system of pests, showing excellent rapid effectiveness and broad-spectrum insecticidal properties. The combination of these two insecticides can achieve synergistic effects, extend the duration of effectiveness, and reduce the risk of drug resistance caused by the long-term use of a single pesticide.

[0004] The present invention provides a composite microemulsion preparation containing avermectin and avermectin and a preparation process thereof. Abamectin and avermectin are prepared into a composite microemulsion preparation, which can fully utilize the stability and dispersibility advantages of the microemulsion system to enhance the insecticidal effect and environmental adaptability of the agent. This preparation form can not only achieve uniform dispersion and long-term stability of the active ingredients, but also improve the efficacy and reduce the dosage requirement, and is an important means to achieve the development of high-efficiency and low-toxic pesticide preparations. Summary of the invention

[0005] In view of the above problems, the present invention provides a composite microemulsion preparation containing cypermethrin and avermectin and a preparation process thereof, so as to solve the problem of drug resistance risk caused by long-term use of a single pesticide in the prior art.

[0006] In order to solve the above technical problems, the present invention provides the following technical solutions: The present invention provides a composite microemulsion preparation containing cypermethrin and avermectin, which is prepared from the following raw materials according to weight percentage: Avermectin 0.5-1.0%, insecticide monochlorfon 10-15%, Tween-80 emulsifier 8-12%, ethylene glycol 5-8%, acetone 10-15%, sodium citrate 1-2%, BHT 0.1-0.3%, and deionized water as the balance.

[0007] The preparation process of the composite microemulsion containing cypermethrin and avermectin described in the present invention comprises the following specific steps: Step S1, optimizing the dissolution rate through a dissolution kinetic model to ensure that the active ingredient is fully dissolved and forms a uniform mother solution; Wherein step S1 also includes the following sub-steps: S1-1, add acetone to the stirring tank, turn on the stirrer, control the speed at 800-1000 rpm, and ensure that the error is less than ±2% through PID feedback control, as shown in formula (1): Formula (1) in, is the error between the target parameter and the actual parameter, are the proportional, integral, and differential coefficients, respectively. is the control signal; S1-2, slowly add the avermectin raw material into acetone, keep the temperature at 40-45°C, stir until completely dissolved, and monitor the dissolution rate using the dissolution kinetics Noyes-Whitney equation, as shown in formula (2): Formula (2) in, is the concentration of dissolved active ingredient, is the saturation concentration, is the diffusion coefficient, is the surface area of ​​the solid particle, is the diffusion layer thickness; S1-3, slowly add the insecticide monohydrate into acetone, continue stirring until it is evenly dissolved and the solubility is close to saturation, and name the obtained mixed solution "mother solution".

[0008] Step S2, stabilizing the pH through a PID algorithm, uniformly dispersing the solubilizer, emulsifier and antioxidant to form an aqueous phase system; Wherein step S2 also includes the following sub-steps: S2-1, in another stirring tank, add deionized water, then add ethylene glycol and Tween-80 emulsifier in sequence, and stir until completely and evenly dissolved; S2-2, add sodium citrate to adjust the pH value of the system to 7.0-8.5, introduce PID control algorithm to monitor pH fluctuation within ±0.1, add antioxidant BHT, stir and disperse evenly to form a "water phase".

[0009] Step S3, using Taguchi experimental design to optimize parameters, combined with DLS real-time monitoring, to ensure uniform distribution of emulsion particle size; Wherein step S3 also includes the following sub-steps: S3-1, slowly add the dissolved active ingredient mother solution into the water phase, and control the constant temperature at 45-50°C; S3-2, gradually increase the stirring speed to 1500-2000 rpm, continue stirring for 15-30 minutes, and optimize the combination of stirring speed, time and temperature parameters by Taguchi experimental design method; S3-3, use a high shear emulsifier at a speed of 8000-10000 rpm for shear emulsification treatment for 10-15 minutes, and monitor the particle size distribution of the emulsion in real time by dynamic light scattering to make the particle size uniform and the standard deviation minimal, as shown in formula (3): Formula (3) in, is the diffusion coefficient, the speed of particle movement, is the Boltzmann constant, is the absolute temperature, is the viscosity of the solution, is the hydraulic radius of the particle.

[0010] Step S4, optimizing the homogenization pressure based on the particle size prediction model, and performing multiple homogenization processes to ensure that the particle size is within a stable range; Wherein step S4 also includes the following sub-steps: S4-1, homogenizing the preliminarily emulsified mixed solution by a high-pressure homogenizer, optimizing the homogenization pressure based on the particle size prediction model, controlling the pressure at 60-100 MPa, repeating 3-5 times, and the particle size prediction model controls the particle size within the range of 50-100 nm; S4-2, monitor the system temperature during homogenization to ensure that it does not exceed 50°C to avoid decomposition of active ingredients.

[0011] Step S5, quickly cooling and removing undissolved particles and impurities through PID temperature control and filtration resistance monitoring; Wherein, in step S5, the following sub-steps are also included: S5-1, the microemulsion system is quickly cooled to room temperature through a cooling system, and PID temperature feedback control is introduced to ensure that the cooling process is accurate and fast, as shown in formula (4): Formula (4) in, is the error between the target parameter and the actual parameter, are the proportional, integral, and differential coefficients, respectively. is the control signal; S5-2, the microemulsion preparation is filtered using a 0.45 μm filter membrane to remove incompletely dissolved particles and impurities, and the filtration rate is monitored by the filtration resistance equation, as shown in formula (5): Formula (5) in, is the filtration rate, is the pressure difference, is the liquid viscosity, is the membrane resistance, and A is the area of ​​the filtration membrane.

[0012] Step S6, using DLS algorithm, HPLC and GC to detect particle size, pH value and component content; Wherein, in step S6, the following sub-steps are also included: S6-1, use a laser particle size analyzer to detect the particle size distribution, ensure that the average particle size and standard deviation meet the standards, and use the DLS algorithm to calculate, as shown in formula (6); Formula (6) Where SD is the standard deviation of the particle size distribution, is the particle size data point, is the average particle size; S6-2, ensure that the pH is within the range of 7.0-8.5 by automated pH monitoring; perform hot storage, low temperature and oscillation tests, use linear regression to predict the stratification trend and stability of the formulation, use HPLC method to detect the content of avermectin, and use GC method to detect the content of chlorpyrifos, as shown in formula (7)-(9): Formula (7) in, is a stratification indicator, It's time. is the initial stratification index value, is the stratified trend coefficient; Formula (8) in, is the avermectin concentration, is the sample detection peak area, The slope of the standard curve is is the standard curve intercept; Formula (9) in, is the content change rate, is the current detected avermectin concentration, is the initial avermectin concentration.

[0013] Step S7, seal and package the product, monitor the storage temperature and humidity, and keep the product in the best storage condition.

[0014] Wherein, in step S7, the following sub-steps are also included: S7-1, fill the microemulsion into high-density polyethylene (HDPE) bottles or light-proof plastic barrels, seal them, store them in a cool, dry, light-proof environment, introduce temperature and humidity sensors to monitor the storage environment data, and set alarm thresholds; S7-2, indicate product information, usage instructions, safety interval and precautions on the label.

[0015] Compared with the prior art, the present invention has the following beneficial effects: The present invention realizes the synergistic effect of the two active ingredients by compounding avermectin and insecticide and combining the characteristics of the microemulsion system, thereby effectively improving the insecticidal effect. The preparation can act on pests quickly, prolong the effective period, and reduce the frequency of medication.

[0016] The present invention adopts dynamic light scattering technology to monitor particle size distribution, combines homogenization pressure optimization and Taguchi experimental design, so that the emulsion particle size is uniformly and stably within the range of 50-100nm, and the good dispersibility significantly improves the absorption utilization rate of the preparation.

[0017] The present invention optimizes the utilization efficiency of active ingredients through microemulsion preparation technology, reduces the amount of pesticide used, reduces the impact on the environment, is highly safe for humans and animals, and meets the needs of green development of modern agriculture.

[0018] The preparation process of the present invention introduces a dissolution kinetic model and a PID feedback control algorithm, optimizes the dissolution, emulsification and homogenization steps, ensures the controllability and efficiency of the production process, and is convenient for large-scale promotion and application. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. It is understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0020] Figure 1 It is a process flow chart of the present invention. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the scope of protection of the present invention. Therefore, the following detailed description of the embodiments of the present invention provided in the drawings is not intended to limit the scope of the invention claimed for protection, but is only for selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the scope of protection of the present invention.

[0022] The present invention provides a composite microemulsion preparation containing cypermethrin and avermectin, which is prepared from the following raw materials according to weight percentage: Avermectin 0.5-1.0%, insecticide monochlorfon 10-15%, Tween-80 emulsifier 8-12%, ethylene glycol 5-8%, acetone 10-15%, sodium citrate 1-2%, BHT 0.1-0.3%, and deionized water as the balance.

[0023] The green vegetable experiment was designed. The test pesticide contained 1% avermectin and 15% insecticide wettable powder. The application dosage was 1.5 times the recommended dosage (5.40g / 20m²). The application method was manual spray. The sampling time was 1 hour, 1 day, 3 days, 7 days, 14 days, 21 days and 30 days after application.

[0024] The soil test was designed on a flat test site with moderate soil moisture. The application dosage was 1.5 times the recommended dosage (2.70 g / 10 m²). The sampling times were 1 hour, 1 day, 3 days, 7 days, 14 days, 21 days and 30 days after application.

[0025] According to the results of dynamic tests, the half-life of avermectin on green vegetables is 3.57-4.55 days, and the degradation rate is more than 92% 14 days after application, and more than 98% after 30 days; the half-life of avermectin in soil is 2.98-3.61 days, and the degradation rate is more than 96% 14 days after application, and more than 99% after 30 days.

[0026] The half-life of insecticide on green vegetables is 3.46-4.01 days, and the dissolution rate is more than 98% 14 days after application, and more than 99% after 30 days; the half-life of insecticide in soil is 3.26-3.34 days, and the dissolution rate exceeds 98%. The following are the key experimental data, see Table 1 for details: Table 1 Key experimental data

[0027] Please refer to Figure 1 The present invention provides a process flow chart of preparing a composite microemulsion preparation containing cypermethrin and avermectin, which comprises the following steps: Step S1, optimizing the dissolution rate through a dissolution kinetic model to ensure that the active ingredient is fully dissolved and forms a uniform mother solution; Wherein step S1 also includes the following sub-steps: S1-1, add acetone to the stirring tank, turn on the stirrer, control the speed at 800-1000 rpm, and ensure that the error is less than ±2% through PID feedback control, as shown in formula (1): Formula (1) in, is the error between the target parameter and the actual parameter, are the proportional, integral, and differential coefficients, respectively. is the control signal; S1-2, slowly add the avermectin raw material into acetone, keep the temperature at 40-45°C, stir until completely dissolved, and monitor the dissolution rate using the dissolution kinetics Noyes-Whitney equation, as shown in formula (2): Formula (2) in, is the concentration of dissolved active ingredient, is the saturation concentration, is the diffusion coefficient, is the surface area of ​​the solid particle, is the diffusion layer thickness; S1-3, slowly add the insecticide monohydrate into acetone, continue stirring until it is evenly dissolved and the solubility is close to saturation, and name the obtained mixed solution "mother solution".

[0028] It should be noted that regarding the evaluation of mixing uniformity of the mother liquor preparation, a laser particle size analyzer is used to detect the particle size distribution of the active ingredient particles in the mother liquor to ensure uniform dissolution and avoid particle agglomeration. Samples are drawn from the mother liquor, diluted to the detection concentration, and tested using a laser particle size analyzer, and the particle size distribution data is recorded. If the particle size distribution does not meet the standards, the stirring time needs to be extended or the stirring speed needs to be increased.

[0029] Observe the microstructure of the mother liquor under a microscope to confirm whether the particles are evenly distributed and whether there are incompletely dissolved particles or agglomerates. The dissolved particles should be evenly distributed without obvious particle agglomeration. The solution should be clear and particle-free with uniform color.

[0030] In addition, if it is found during the dissolution process that a certain ingredient (such as chlorpyrifos or avermectin) is difficult to achieve an ideal dissolution state, the dissolution effect can be optimized by appropriately increasing or decreasing the proportion of a certain ingredient.

[0031] Step S2, stabilizing the pH through a PID algorithm, uniformly dispersing the solubilizer, emulsifier and antioxidant to form an aqueous phase system; Wherein step S2 also includes the following sub-steps: S2-1, in another stirring tank, add deionized water, then add ethylene glycol and Tween-80 emulsifier in sequence, and stir until completely and evenly dissolved; S2-2, add sodium citrate to adjust the pH value of the system to 7.0-8.5, introduce PID control algorithm to monitor pH fluctuation within ±0.1, add antioxidant BHT, stir and disperse evenly to form a "water phase".

[0032] It should be noted that in order to ensure the uniformity of the aqueous phase, it is necessary to evaluate the uniformity of dissolution and dispersion in the system after the solubilizer, emulsifier and antioxidant are mixed. Using liquid transmittance detection, the uniformly dissolved aqueous phase system should show consistent transmittance, without visible precipitation or particles. Use a spectrophotometer to detect the transmittance of the aqueous phase, and take samples from the top, middle and bottom of the mixed liquid to measure the change in transmittance. The indicator requires that the transmittance change range does not exceed ±2%.

[0033] Step S3, using Taguchi experimental design to optimize parameters, combined with DLS real-time monitoring, to ensure uniform distribution of emulsion particle size; Wherein step S3 also includes the following sub-steps: S3-1, slowly add the dissolved active ingredient mother solution into the water phase, and control the constant temperature at 45-50°C; S3-2, gradually increase the stirring speed to 1500-2000 rpm, continue stirring for 15-30 minutes, and optimize the stirring speed, time and temperature parameter combination by Taguchi experimental design method; S3-3, use a high shear emulsifier at a speed of 8000-10000 rpm for shear emulsification treatment for 10-15 minutes, and monitor the particle size distribution of the emulsion in real time by dynamic light scattering to make the particle size uniform and the standard deviation minimal, as shown in formula (3): Formula (3) in, is the diffusion coefficient, the speed of particle movement, is the Boltzmann constant, is the absolute temperature, is the viscosity of the solution, is the hydraulic radius of the particle.

[0034] It should be noted that the standard deviation is a key indicator for measuring the uniformity of the particle size distribution of the emulsion. It needs to be obtained through dynamic light scattering (DLS) technology or other particle size detection methods, and is used to evaluate the stability and uniformity of the emulsion.

[0035] Use DLS or laser particle size analyzer to measure the particle size distribution data of the emulsion sample, record the particle size values ​​of different particles, calculate the average particle size and standard deviation. A lower standard deviation indicates a more uniform particle size distribution. The average particle size should be in the range of 50-100nm, and the standard deviation should be less than 10% to ensure uniformity of distribution. Too large a standard deviation may cause emulsion instability or affect drug absorption, while too small a standard deviation may increase preparation costs and increase the risk of agglomeration.

[0036] Step S4, optimizing the homogenization pressure based on the particle size prediction model, and performing multiple homogenization processes to ensure that the particle size is within a stable range; Wherein step S4 also includes the following sub-steps: S4-1, homogenizing the preliminarily emulsified mixed solution by a high-pressure homogenizer, optimizing the homogenization pressure based on the particle size prediction model, controlling the pressure at 60-100 MPa, repeating 3-5 times, and the particle size prediction model controls the particle size within the range of 50-100 nm; S4-2, monitor the system temperature during homogenization to ensure that it does not exceed 50°C to avoid decomposition of active ingredients.

[0037] It should be noted that during the homogenization stage, the particle size convergence condition is the key control point to ensure that the emulsion particle size reaches the target range and is stable. The lack of a convergence standard may lead to uneven particle size distribution or decreased emulsion stability. The particle size convergence condition refers to the process of multiple homogenization treatments so that the particle size of the emulsion gradually tends to be stable, reaches the set target range, and the particle size change rate is lower than a specific threshold.

[0038] Adjust the parameters of the high-pressure homogenizer to control the pressure range of 60-100MPa, optimize the particle size through pressure regulation, and homogenize 3-5 times. Ensure that the temperature does not exceed 50°C during the treatment process through temperature control to prevent degradation of active ingredients. After the initial homogenization, record the particle size distribution of the emulsion, adjust the pressure or increase the number of homogenization times, and monitor whether the particle size gradually approaches the target range (50-100nm). When the particle size change rate is less than 5% and the PDI is less than 0.1, confirm that the particle size has converged.

[0039] Step S5, quickly cooling and removing undissolved particles and impurities through PID temperature control and filtration resistance monitoring; Wherein, in step S5, the following sub-steps are also included: S5-1, the microemulsion system is quickly cooled to room temperature through a cooling system, and PID temperature feedback control is introduced to ensure that the cooling process is accurate and fast, as shown in formula (4): Formula (4) in, is the error between the target parameter and the actual parameter, are the proportional, integral, and differential coefficients, respectively. is the control signal; S5-2, the microemulsion preparation is filtered using a 0.45 μm filter membrane to remove incompletely dissolved particles and impurities, and the filtration rate is monitored by the filtration resistance equation, as shown in formula (5): Formula (5) in, is the filtration rate, is the pressure difference, is the liquid viscosity, is the membrane resistance, and A is the area of ​​the filtration membrane.

[0040] It should be noted that the quality of the filtered solution directly affects the uniformity, stability and final effect of the product. The quality of the filtered solution should meet the following requirements: no obvious undissolved particles or impurities, the particle size is in line with the target range (50-100nm), the solution has good uniformity, the concentration of key components is consistent, the solution has high light transmittance, and there is no stratification or precipitation.

[0041] Specific detection standards and methods: place the solution sample in a transparent glass container and observe whether there are suspended particles or precipitation under natural light or white light. If there are particles or precipitation, the filtration time needs to be extended or the filter membrane pore size needs to be changed.

[0042] Particle size distribution detection uses dynamic light scattering (DLS) equipment to measure particle size distribution. Samples are taken from different sampling points (top, middle, and bottom) to ensure uniformity and detect whether there are large particles >100nm. If so, repeat filtration or adjust filtration conditions.

[0043] Step S6, using DLS algorithm, HPLC and GC to detect particle size, pH value and component content; Wherein, in step S6, the following sub-steps are also included: S6-1, use a laser particle size analyzer to detect the particle size distribution, ensure that the average particle size and standard deviation meet the standards, and use the DLS algorithm to calculate, as shown in formula (6); Formula (6) Where SD is the standard deviation of the particle size distribution, is the particle size data point, is the average particle size; S6-2, ensure that the pH is within the range of 7.0-8.5 by automated pH monitoring; perform hot storage, low temperature and oscillation tests, use linear regression to predict the stratification trend and stability of the formulation, use HPLC method to detect the content of avermectin, and use GC method to detect the content of chlorpyrifos, as shown in formula (7)-(9): Formula (7) in, is a stratification indicator, It's time. is the initial stratification index value, is the stratified trend coefficient; Formula (8) in, is the avermectin concentration, is the sample detection peak area, The slope of the standard curve is is the standard curve intercept; Formula (9) in, is the content change rate, is the current detected avermectin concentration, is the initial avermectin concentration.

[0044] It should be noted that hot storage and low temperature testing are important steps to evaluate the stability of microemulsion preparations under extreme storage conditions. The purpose is to ensure that the physical and chemical properties of the product remain stable under temperature changes.

[0045] The hot storage test simulates the stability of the product under high-temperature storage conditions and detects changes in its appearance, particle size, ingredient content, stratification or precipitation; the temperature range is 40℃±2℃, and the test time is 14 days, 30 days, and 90 days. The specific time depends on the use of the preparation or stability requirements. The container is required to be a high-density polyethylene (HDPE) bottle or the actual packaging container of the preparation and is well sealed. The low-temperature test simulates the stability of the product under low-temperature storage or transportation conditions to detect whether coagulation, stratification, precipitation or particle size increase occurs. The temperature range is 0℃±2℃, and the test time is 7 days, 14 days, and 30 days. The container is required to be stored in an actual packaging container and sealed.

[0046] The operating steps of hot storage and low-temperature tests are as follows: take representative samples, pack them into actual packaging containers, seal them and mark them. The hot storage samples are placed in a constant temperature box (40℃±2℃), and the low-temperature samples are placed in a low-temperature box (0℃±2℃). For the hot storage test, samples are taken for inspection at 0 days, 14 days, 30 days, and 90 days respectively. For the low-temperature test, samples are taken for inspection at 0 days, 7 days, 14 days, and 30 days respectively. After each sampling, various indicators are tested immediately, and the appearance, particle size distribution, component content, and pH value data are recorded.

[0047] Step S7, seal and package the product, monitor the storage temperature and humidity, and keep the product in the best storage condition.

[0048] Wherein, in step S7, the following sub-steps are also included: S7-1, fill the microemulsion into high-density polyethylene (HDPE) bottles or light-proof plastic barrels, seal them, store them in a cool, dry, light-proof environment, introduce temperature and humidity sensors to monitor the storage environment data, and set alarm thresholds; S7-2, indicate product information, usage instructions, safety interval and precautions on the label.

[0049] It should be noted that during the storage process, if the environmental conditions exceed the recommended range, the stability of the microemulsion preparation may decrease. Common causes of abnormal conditions include: abnormal temperature. High temperature may accelerate the degradation of avermectin and insecticide, causing stratification, precipitation or a decrease in the content of active ingredients; low temperature may cause the precipitation of emulsifiers or solubilizers, resulting in emulsion instability; abnormal humidity. High humidity may cause condensation of water vapor inside and outside the packaging container, resulting in changes in the properties of the emulsion; low humidity may cause packaging materials to fail or the product to dry out; abnormal light. Direct strong light may cause photodegradation of avermectin and insecticide, affecting the effectiveness of the product.

[0050] Measures for handling abnormal situations and handling of abnormal temperatures: If it is too hot, immediately transfer the product to a cool environment with suitable temperature. Take samples to test particle size distribution, component content and appearance changes, and evaluate product stability. If the particle size, component content or appearance exceeds the standard range, re-filter or adjust storage conditions. If it is too cold, slowly heat the product to room temperature to avoid deformation of the container or instability of the emulsion due to excessive temperature difference. After standing for 24 hours, check whether the emulsion has returned to a clear state. If precipitation or abnormal particle size distribution occurs, stir or re-emulsify.

[0051] Handling of abnormal humidity: Check the sealing of the packaging container at high humidity. If leakage or condensation is found, replace the qualified packaging. Use a dehumidifier to reduce the humidity of the storage environment to 30%-60%. Take samples to test the moisture content and emulsion appearance, and evaluate whether additional treatment is needed. Ensure that the packaging container is intact at low humidity to avoid container rupture due to dryness. Use humidification equipment to adjust the humidity to the recommended range. Check the fluidity and emulsion properties of the product to ensure that the uniformity is not affected.

[0052] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention has various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A composite microemulsion preparation containing cypermethrin and avermectin, characterized in that: The composite microemulsion preparation is prepared from the following raw materials according to weight percentage: Avermectin 0.5-1.0%, insecticide monochlorfon 10-15%, Tween-80 emulsifier 8-12%, ethylene glycol 5-8%, acetone 10-15%, sodium citrate 1-2%, BHT 0.1-0.3%, and deionized water as the balance.

2. A process for preparing a composite microemulsion containing cypermethrin and avermectin, specifically applied to the composite microemulsion according to claim 1, characterized in that: The preparation process includes: Step S1, optimizing the dissolution rate through a dissolution kinetic model to ensure that the active ingredient is fully dissolved and forms a uniform mother solution; Step S2, stabilizing the pH through a PID algorithm, uniformly dispersing the solubilizer, emulsifier and antioxidant to form an aqueous phase system; Step S3, using Taguchi experimental design to optimize parameters, combined with DLS real-time monitoring, to ensure uniform distribution of emulsion particle size; Step S4, optimizing the homogenization pressure based on the particle size prediction model, and performing multiple homogenization processes to ensure that the particle size is within a stable range; Step S5, quickly cooling and removing undissolved particles and impurities through PID temperature control and filtration resistance monitoring; Step S6, using DLS algorithm, HPLC and GC to detect particle size, pH value and component content; Step S7, seal and package the product, monitor the storage temperature and humidity, and keep the product in the best storage condition.

3. The process for preparing a composite microemulsion containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein step S1 also includes the following sub-steps: S1-1, add acetone to the stirring tank, turn on the stirrer, control the speed at 800-1000 rpm, and ensure that the error is less than ±2% through PID feedback control, as shown in formula (1): Formula (1) in, is the error between the target parameter and the actual parameter, are the proportional, integral, and differential coefficients, respectively. is the control signal; S1-2, slowly add the avermectin raw material into acetone, keep the temperature at 40-45°C, stir until completely dissolved, and monitor the dissolution rate using the dissolution kinetics Noyes-Whitney equation, as shown in formula (2): Formula (2) in, is the concentration of dissolved active ingredient, is the saturation concentration, is the diffusion coefficient, is the surface area of ​​the solid particle, is the diffusion layer thickness; S1-3, slowly add the insecticide monohydrate into acetone, continue stirring until it is evenly dissolved and the solubility is close to saturation, and name the obtained mixed solution "mother solution".

4. The process for preparing a composite microemulsion preparation containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein step S2 also includes the following sub-steps: S2-1, in another stirring tank, add deionized water, then add ethylene glycol and Tween-80 emulsifier in sequence, and stir until completely and evenly dissolved; S2-2, add sodium citrate to adjust the pH value of the system to 7.0-8.5, introduce PID control algorithm to monitor pH fluctuation within ±0.1, add antioxidant BHT, stir and disperse evenly to form "aqueous phase".

5. The process for preparing a composite microemulsion preparation containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein step S3 also includes the following sub-steps: S3-1, slowly add the dissolved active ingredient mother solution into the water phase, and control the constant temperature at 45-50°C; S3-2, gradually increase the stirring speed to 1500-2000 rpm, continue stirring for 15-30 minutes, and optimize the stirring speed, time and temperature parameter combination by Taguchi experimental design method; S3-3, use a high shear emulsifier at a speed of 8000-10000 rpm for shear emulsification treatment for 10-15 minutes, and monitor the particle size distribution of the emulsion in real time by dynamic light scattering to make the particle size uniform and the standard deviation minimal, as shown in formula (3): Formula (3) in, is the diffusion coefficient, the speed of particle movement, is the Boltzmann constant, is the absolute temperature, is the viscosity of the solution, is the hydraulic radius of the particle.

6. The process for preparing a composite microemulsion containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein step S4 also includes the following sub-steps: S4-1, homogenizing the preliminarily emulsified mixed solution by a high-pressure homogenizer, optimizing the homogenization pressure based on the particle size prediction model, controlling the pressure at 60-100 MPa, repeating 3-5 times, and the particle size prediction model controls the particle size within the range of 50-100 nm; S4-2, monitor the system temperature during homogenization to ensure that it does not exceed 50°C to avoid decomposition of active ingredients.

7. The process for preparing a composite microemulsion preparation containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein, in step S5, the following sub-steps are also included: S5-1, the microemulsion system is quickly cooled to room temperature through a cooling system, and PID temperature feedback control is introduced to ensure that the cooling process is accurate and fast, as shown in formula (4): Formula (4) in, is the error between the target parameter and the actual parameter, are the proportional, integral, and differential coefficients, respectively. is the control signal; S5-2, the microemulsion preparation is filtered using a 0.45 μm filter membrane to remove incompletely dissolved particles and impurities, and the filtration rate is monitored by the filtration resistance equation, as shown in formula (5): Formula (5) in, is the filtration rate, is the pressure difference, is the liquid viscosity, is the membrane resistance, and A is the area of ​​the filtration membrane.

8. The process for preparing a composite microemulsion preparation containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein, in step S6, the following sub-steps are also included: S6-1, use a laser particle size analyzer to detect the particle size distribution, ensure that the average particle size and standard deviation meet the standards, and use the DLS algorithm to calculate, as shown in formula (6); Formula (6) Where SD is the standard deviation of the particle size distribution, is the particle size data point, is the average particle size; S6-2, ensure that the pH is within the range of 7.0-8.5 by automated pH monitoring; perform hot storage, low temperature and oscillation tests, use linear regression to predict the stratification trend and stability of the formulation, use HPLC method to detect the content of avermectin, and use GC method to detect the content of chlorpyrifos, as shown in formula (7)-(9): Formula (7) in, is a stratification indicator, It's time. is the initial stratification index value, is the stratified trend coefficient; Formula (8) in, is the avermectin concentration, is the sample detection peak area, The slope of the standard curve is is the standard curve intercept; Formula (9) in, is the content change rate, is the current detected avermectin concentration, is the initial avermectin concentration.

9. The process for preparing a composite microemulsion preparation containing cypermethrin and avermectin according to claim 2, characterized in that: Wherein, in step S7, the following sub-steps are also included: S7-1, fill the microemulsion into high-density polyethylene (HDPE) bottles or light-proof plastic barrels, seal them, store them in a cool, dry, light-proof environment, introduce temperature and humidity sensors to monitor the storage environment data, and set alarm thresholds; S7-2, indicate product information, usage instructions, safety interval and precautions on the label.

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