A kind of avermectin quick-release and sustained-release dual-effect solid pesticide and preparation method thereof

Abstract

The invention discloses an avermectin quick-release and sustained-release dual-effect solid pesticide and a preparation method thereof. The composition is as follows: avermectin active ingredient 1%-20%, surfactant 1%-30%, sustained-release carrier 0.5%-10%, quick-release carrier 40%-90%. The quick-release and sustained-release dual-effect solid pesticide of the present invention can not only combine systems with different release characteristics in one-step preparation to play a synergistic role, but also integrates the micron and nano dual-size characteristics, giving the system richer properties, and its solid preparation form can also significantly improve the preparation stability and storage and transportation convenience and safety, overcome the problems of agglomeration, flocculation, sedimentation caused by the interaction of electrostatic attraction and van der Waals forces during the water dispersion process, and maintain its ideal application effect.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and specifically relates to an avermectin quick-release and sustained-release dual-effect solid pesticide and a preparation method thereof. Background Art

[0002] Pesticides are an important material basis for preventing and controlling agricultural pests and diseases and promoting stable and high grain production. At present, my country still mainly uses traditional formulations such as emulsifiable concentrates and wettable powders. These traditional formulations have problems such as the large use of organic solvents and adjuvants, dust drift, and poor water dispersibility, resulting in a loss of up to 70%-90% of the active ingredients in the use of pesticides. If the protected crops are taken as the actual target, the effective utilization rate is generally less than 30%; if calculated based on the actual amount of pesticide received by the pests, the utilization rate is even less than 0.1%. In addition, the effective period of traditional preparations is also relatively low, and it is difficult to maintain the effective concentration above the effective dose for pest control for a long time, so multiple applications are required. This not only leads to a waste of resources, but also causes serious pollution to the soil, water and atmosphere. Therefore, improving the performance of traditional preparations and developing dual-effect preparations with excellent water dispersibility and stability, as well as rapid release and sustained release are important ways to improve the effective utilization rate of traditional preparations.

[0003] In recent years, carrier-coated sustained-release pesticide systems such as microspheres, microcapsules, and gels have attracted more and more attention in the field of pesticide formulation processing. On the one hand, the sustained-release system can effectively inhibit the decomposition and loss of pesticides caused by environmental factors such as light, heat, rain, soil, microorganisms, and other chemical substances, improve the stability of the formulation, inhibit the volatilization of pesticides, mask the odor of pesticides, reduce contact toxicity, inhalation toxicity and pesticide damage, and reduce irritation to humans and animals. On the other hand, it can effectively extend the effective period of pesticide formulations, reduce the dosage and number of applications, and reduce the toxicity of pesticides to users and non-target organisms. With the sharp increase in agricultural labor costs and the improvement of people's environmental awareness, sustained-release pesticide formulations have gradually become one of the development directions of future pesticide formulations.

[0004] At present, the system with both rapid release and sustained release functions in the agricultural field is microcapsule suspension-suspension concentrate. The main disadvantage of this type of pesticide system is the stability of the liquid preparation. In addition, the rapid release and sustained release parts of the preparation are independent of each other, and the drug-loaded particles are large in size, which is easy to produce sedimentation. Usually, more stabilizers and suspending agents need to be added to maintain the stability of the system. The liquid dosage form is easily disturbed by the external environment and destroyed, which is inconvenient to store and transport. In actual application, the rapid and sustained release effects are also difficult to coordinate.

[0005] Nanoparticles have small size effect, interface effect and high permeability effect, which can improve the stability and water dispersibility of poorly soluble pesticides, promote target deposition and dose transfer, reduce loss, and thus improve the utilization rate of pesticides. Therefore, the use of nanomaterials and technologies to construct pesticide rapid-release nanoparticles can not only enable the preparation to exert its efficacy in a shorter period of time and quickly control the spread of pests and diseases, but also significantly improve the dispersibility, effectiveness and safety of pesticides. Studies have shown that the smaller the particle size of the nanoparticles, the higher the dispersion rate and suspension rate after entering the water. As the specific surface area of ​​the particles increases, the leaf surface attachment rate and deposition performance are also higher, that is, the nano-scale dispersed drug-carrying system is conducive to the rapid release of pesticides and the improvement of biological activity. For the sustained-release system, according to current literature reports and the team's previous research results, the larger the particle size of the drug-carrying particles and the thicker the shell material, the more conducive to extending the release time of the drug and improving the protection performance of the pesticide. Therefore, in the field of pesticide formulation processing, how to make the system have rapid effect, sustained release, stability and high efficiency at the same time, and how to integrate nano and micro drug delivery systems has always been a research difficulty in this field. Summary of the invention

[0006] The purpose of the present invention is to provide an avermectin quick-release and sustained-release dual-effect solid pesticide and a preparation method thereof.

[0007] The avermectin fast-release and sustained-release dual-effect solid pesticide of the present invention exists in two particle sizes after being dispersed in water, wherein the effective ingredients in the fast-release drug-loaded part are of nanometer size of 1-100 nm after being dispersed in water, and the effective ingredients in the sustained-release drug-loaded part are of micrometer size of 1-5 μm after being dispersed in water.

[0008] The avermectin quick-release and sustained-release dual-effect solid pesticide provided by the present invention has the following composition in parts by weight:

[0009]

[0010] In the above-mentioned avermectin quick-release and sustained-release dual-effect solid pesticide, the avermectin active ingredients include one or more of type B1 avermectin, type B2 avermectin and avermectin benzoate.

[0011] In the above-mentioned avermectin-based rapid-release and sustained-release dual-effect solid pesticide, the surfactant should be understood to be a substance that can significantly change the interface state of the solution system.

[0012] The surfactant contains both hydrophilic groups and hydrophobic groups in its molecules.

[0013] The hydrophilic group is a polar group, such as carboxylic acid, sulfonic acid, sulfuric acid, amino group, hydroxyl group, amide group, etc.; while the hydrophobic group is usually a non-polar hydrocarbon chain.

[0014] The surfactant may be an anionic surfactant, a nonionic surfactant or a combination thereof.

[0015] The anionic surfactant may be selected from: maleic rosin polyoxyethylene-oxypropylene ether sulfonate, alkylphenol polyoxyethylene ether phosphate salt, monolauryl ether phosphate salt, didodecyl ether phosphate salt, octyl ether phosphate, fatty alcohol polyoxyethylene ether carboxylate, polycarboxylate and lignin sulfonate;

[0016] The nonionic surfactant can be selected from: phenolic resin polyoxyethylene ether, styrylphenol polyoxyethylene ether, alkylphenol formaldehyde resin polyoxyethylene ether, isopropylphenylphenol polyoxyethylene ether formaldehyde condensate, polyvinyl alcohol, castor oil polyoxyethylene ether, polyvinyl pyrrolidone, polyoxyethylene sorbitan monooleate, sorbitan oleate and polyoxyethylene polyoxypropylene block copolymer.

[0017] The sustained-release carrier is a polylactic acid compound, specifically at least one of polylactic acid and polylactic acid-glycolic acid copolymer.

[0018] Laboratory studies have found that polylactic acid compounds can form a good micron-scale drug-carrying system during the oil-water two-phase film formation and solvent volatilization process of this process, encapsulating or adsorbing a portion of avermectin compounds to achieve slow release of the drug, and at the same time, with the help of the spacing effect of the rapid-release carrier and the dispersing effect of the surfactant, avoid large-scale aggregation of the micron system.

[0019] The rapid-release carrier is at least one of sodium butyrate, sodium benzoate, sodium dodecyl sulfate, urea and lactose.

[0020] The rapid-release carrier not only plays the role of a supporting carrier in the formulation composition, so that the pesticide compound is dispersed in the carrier in the form of particles, but also accelerates the dispersion and dissolution of the drug-loaded particles in water by virtue of its high solubility and rapid dispersibility in water. Some avermectin compounds will be adsorbed on the surface of the rapid-release carrier. When dispersed with water, the drug-loaded particles can prevent drug aggregation, flocculation and precipitation through electrostatic action or steric hindrance, ensuring that the rapid-release drug-loaded particles are suspended in water in the form of nanoparticles as the carrier dissolves.

[0021] The above-mentioned avermectin quick-release and sustained-release dual-effect solid pesticide preparation is Figure 1 The process flow shown is prepared by a method comprising the following steps:

[0022] (1) dissolving the sustained-release carrier in an organic solvent to obtain a transparent oil phase A;

[0023] (2) adding the avermectin active ingredient and the surfactant into the oil phase A and dissolving them completely to obtain a uniformly dispersed transparent oil phase B;

[0024] (3) slowly adding the oil phase B dropwise into the water, shearing and emulsifying, to obtain a mixed phase C;

[0025] (4) adding a quick-release carrier to the mixed phase C under stirring to obtain a mixture D;

[0026] (5) The solvent and water in D are removed to obtain an avermectin-based rapid-release and sustained-release dual-effect solid pesticide.

[0027] In step (1) of the above method, the organic solvent is a low-boiling point organic solvent that can dissolve both the sustained-release carrier and the avermectin active ingredient and is immiscible with water.

[0028] On the one hand, it is to ensure that avermectin pesticides are dissolved in molecular state, which is convenient for the assembly process of their micron and nano systems. On the other hand, it is to facilitate the removal of solvents in the subsequent removal of solvents. The water-immiscible solvent can cause the sustained-release carrier to gather at the oil-water interface. Later, as the organic solvent is removed, the sustained-release carrier can precipitate or self-assemble at the interface, thereby adsorbing or encapsulating the pesticide compounds and realizing the construction of a sustained-release system.

[0029] The organic solvent may specifically be dichloromethane and / or chloroform.

[0030] At present, the construction of nano pesticide particles generally requires the assistance of external crushing means such as grinding and shearing, which not only consumes a lot of energy, but also obtains uneven particle size distribution, and also pollutes the system due to problems such as dissolution and shedding of grinding beads, affecting the final quality of the product. The preparation method of the present invention does not require the use of high-energy consumption equipment such as grinders, has a simple preparation process, is easy to control, has stable product quality, good reproducibility, improves production efficiency and pesticide utilization, and saves production costs.

[0031] In the present invention, the amount of the sustained-release carrier is not more than 10%, and the amount of the rapid-release carrier is not less than 40%, otherwise the water dispersibility of the solid pesticide will be affected, thereby affecting the rapid-release and sustained-release effects.

[0032] The present invention creatively integrates the micron-level and nano-level drug-carrying systems of pesticides through long-term exploration and research, and adopts a one-step preparation method to construct a kind of avermectin-type quick-release-slow-release dual-effect solid pesticide. When the preparation is used, the nano-level drug-carrying particles quickly disperse and release the drug, exerting the quick-release function, and at the same time, the small size effect, large specific surface effect, interface effect and high permeability characteristics of the nanoparticles are conducive to increasing the adhesion and permeability of the drug on the crop leaf surface, thereby improving its bioavailability. In contrast, the active ingredients of the pesticide in the micron-level slow-release carrier slowly release the pesticide due to the encapsulation / adsorption effect of the slow-release carrier, which can not only prolong the release time of the drug, but also maintain the active concentration of the pesticide above the effective dose for a long time, ensure the effectiveness and persistence of the agent, reduce the operating cost, and improve the ecological and environmental benefits. In the composition of the preparation, the nano- and micron-level drug-carrying systems are mutually integrated, which not only ensures the uniformity of the system, but also avoids the agglomeration and aggregation between the single systems. In addition, the preparation is in the form of a solid preparation, which is less affected by the external environment than the liquid preparation, and the stability and shelf life are significantly improved, which is convenient for packaging, storage and transportation.

[0033] The quick-release and sustained-release dual-effect solid pesticide of the present invention can not only combine systems with different release characteristics in a one-step preparation to exert synergistic effects, but also integrates the dual-size characteristics of micrometer and nanometer, giving the system richer properties. Its solid preparation form can also significantly improve the stability of the preparation and the convenience and safety of storage and transportation, overcome the problems of agglomeration, flocculation, sedimentation, etc. caused by the interaction of electrostatic attraction and van der Waals forces during the water dispersion process, and maintain its ideal application effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The present invention is a process flow chart for preparing the avermectin quick-release and sustained-release dual-effect solid pesticide.

[0035] Figure 2 This is the particle size distribution diagram of the B1 type avermectin rapid-release and sustained-release dual-effect powder prepared in Example 1 of the present invention after entering water.

[0036] Figure 3 It is a comparison chart of the sustained release performance of the rapid-release-sustained-release dual-effect preparation, the pure sustained-release preparation of ethyl cellulose, and the dual-effect preparation with ethyl cellulose as a sustained-release carrier in Example 8 of the present invention.

[0037] Figure 4 This is a comparison chart of leaf adhesion and retention performance of the rapid-release-sustained-release dual-effect preparation and the pure sustained-release preparation of ethyl cellulose in Example 9 of the present invention.

[0038] Figure 5 This is the sustained release curve of the preparation prepared in Comparative Example 1. DETAILED DESCRIPTION

[0039] The present invention is further described in detail below in conjunction with specific embodiments, and the examples provided are only for illustrating the present invention, rather than for limiting the scope of the present invention. The examples provided below can be used as a guide for further improvements by those of ordinary skill in the art, and do not constitute a limitation of the present invention in any way.

[0040] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0041] Example 1: Preparation of 1% mass concentration of B1 type avermectin rapid-release and sustained-release dual-effect powder

[0042] The implementation steps of this embodiment are as follows:

[0043] (1) Weigh 0.7 g of polylactic acid (Shandong Academy of Pharmaceutical Sciences) and dissolve it in 8 mL of dichloromethane (Sinopharm Chemical Reagent Beijing Co., Ltd.). After complete dissolution, a transparent oil phase A is obtained;

[0044] (2) 0.1 g of B1 type avermectin technical (Qilu Pharmaceutical (Inner Mongolia) Co., Ltd.), 0.8 g of Nongru 600 (styrylphenol polyoxyethylene ether, Cangzhou Hongyuan Agrochemical Co., Ltd.) and 0.8 g of Nongru 700 (alkylphenol formaldehyde resin polyoxyethylene ether, Cangzhou Hongyuan Agrochemical Co., Ltd.) were added to A and completely dissolved to obtain a transparent oil phase B;

[0045] (3) Slowly add the oil phase B dropwise into 15 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0046] (4) adding 7.6 g of sodium benzoate to the mixed phase C while stirring at 500 rpm to obtain a mixture D;

[0047] (5) The mixture D is heated in an oven at 45° C., and after the dichloromethane and water are completely volatilized, the mixture is pulverized again to obtain a B1 type avermectin rapid-release and sustained-release dual-effect pesticide powder.

[0048] The B1 type avermectin rapid-release and sustained-release dual-effect powder prepared in this example was dispersed with standard hard water, and the wetting time was 15 s. The average particle size of the nano-scale drug-carrying particles in the drug-carrying system was measured by a Malvern particle size analyzer to be 25 nm, and the average particle size of the micron-scale drug-carrying particles was 2.0 microns.

[0049] Example 2: Preparation of 20% mass concentration of avermectin benzoate rapid-release and sustained-release dual-effect tablets

[0050] The implementation steps of this embodiment are as follows:

[0051] (1) Weigh 0.3 g of polylactic acid and dissolve it in 5 mL of dichloromethane to obtain a transparent oil phase A after it is completely dissolved;

[0052] (2) 2 g of emamectin benzoate technical (Qilu Shenghua Pharmaceutical Co., Ltd.) and 1.5 g of Nongru 600 were added to A and completely dissolved to obtain a transparent oil phase B;

[0053] (3) Slowly add the oil phase B dropwise into 10 mL of water and shear at 8000 rpm to obtain a mixed phase C;

[0054] (4) Add 6.2 g of sodium n-butyrate (B&K Technology Co., Ltd.) to the mixed phase C under stirring at 500 rpm to obtain a mixture D;

[0055] (5) heating the mixture D in an oven at 45° C. until the dichloromethane and water are completely volatilized, and then pulverizing the mixture again to obtain an emamectin benzoate rapid-release and sustained-release dual-effect powder;

[0056] (6) The dual-effect powder obtained above is placed in a tablet press for tableting to prepare avermectin benzoate rapid-release and sustained-release dual-effect tablets.

[0057] The avermectin benzoate rapid-release and sustained-release dual-effect tablets prepared in this example were dispersed with standard hard water, and the wetting time was 42 seconds. The average particle size of the nano-sized drug-loaded particles in the drug-loaded system was 52 nm, and the average particle size of the micro-sized drug-loaded particles was 2.8 microns.

[0058] Example 3: Preparation of 5% mass concentration of B1 type avermectin rapid-release and sustained-release dual-effect granules

[0059] The implementation steps of this embodiment are as follows:

[0060] (1) Weigh 0.5 g of polylactic acid and dissolve it in 4 mL of dichloromethane to obtain a transparent oil phase A after complete dissolution;

[0061] (2) 0.5 g of B1 type avermectin technical and 2 g of polyvinyl alcohol (Shanghai Yuanye Biotechnology Co., Ltd.) were added to A and completely dissolved to obtain a transparent oil phase B;

[0062] (3) Slowly add the oil phase B dropwise into 13 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0063] (4) Add 7 g of lactose (Shanghai Yuanye Biotechnology Co., Ltd.) to the mixed phase C under stirring at 500 rpm to obtain a mixture D;

[0064] (5) The mixture D is heated in an oven at 50° C., and after the dichloromethane and water are completely volatilized, the mixture is pulverized again to obtain a B1 type avermectin rapid-release and sustained-release dual-effect powder.

[0065] (6) After adding an appropriate amount of binder (1% PVA aqueous solution, amount is 2%) to the obtained dual-effect powder, the powder is placed in an extrusion granulator for extrusion granulation and the moisture is dried to obtain B1 type avermectin rapid-release and sustained-release dual-effect granules.

[0066] The B1 type avermectin rapid-release and sustained-release dual-effect granules prepared in this example were dispersed with standard hard water, and the wetting time was 32 seconds. The average particle size of the nano-sized drug-carrying particles in the drug-carrying system was 45 nm, and the average particle size of the micro-sized drug-carrying particles was 3.1 microns.

[0067] Example 4: Preparation of 4% mass concentration of B2-type avermectin rapid-release and sustained-release dual-effect powder

[0068] The implementation steps of this embodiment are as follows:

[0069] (1) Weigh 0.5 g of polylactic acid and dissolve it in 4 mL of dichloromethane to obtain a transparent oil phase A after complete dissolution;

[0070] (2) 0.4 g of B2-type avermectin technical (Hebei Xingbai Agricultural Technology Co., Ltd.), 0.05 g of Nongru 600 and 0.05 g of maleic rosin polyoxyethylene-oxypropylene ether sulfonate (Jiangsu Qingyu Chemical Technology Co., Ltd.) were added to A and completely dissolved to obtain a transparent oil phase B;

[0071] (3) Slowly add the oil phase B dropwise into 12 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0072] (4) adding 9.0 g of sodium benzoate to the mixed phase C while stirring at 500 rpm to obtain a mixture D;

[0073] (5) The mixture D is heated in an oven at 45° C., and after the dichloromethane and water are completely evaporated, the mixture is pulverized again to obtain a B2-type avermectin rapid-release and sustained-release dual-effect powder.

[0074] The B2 type avermectin rapid-release and sustained-release dual-effect powder prepared in this example was dispersed with standard hard water, and the wetting time was 15 seconds. The average particle size of the nano-scale drug-carrying particles in the drug-carrying system was 67 nm, and the average particle size of the micro-scale drug-carrying particles was 3.3 microns.

[0075] Example 5: Preparation of 10% mass concentration of emamectin benzoate rapid-release and sustained-release dual-effect tablets

[0076] The implementation steps of this embodiment are as follows:

[0077] (1) Weigh 0.05 g of poly(lactic acid-co-glycolic acid) (Shandong Academy of Pharmaceutical Sciences) and dissolve it in 3 mL of dichloromethane to obtain a transparent oil phase A after complete dissolution;

[0078] (2) 1 g of emamectin benzoate technical and 3 g of lignin sulfonate (Shanghai Yuanye Biotechnology Co., Ltd.) were added to A and completely dissolved to obtain a transparent oil phase B;

[0079] (3) Slowly add the oil phase B dropwise into 8 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0080] (4) adding 5.95 g of sodium benzoate to the mixed phase C while stirring at 500 rpm to obtain a mixture D;

[0081] (5) The mixture D is freeze-dried to remove dichloromethane and water, and then pulverized again to obtain an avermectin benzoate rapid-release and sustained-release dual-effect powder.

[0082] (6) The dual-effect powder obtained above is placed in a tablet press for tableting to prepare avermectin benzoate rapid-release and sustained-release dual-effect tablets.

[0083] The avermectin benzoate rapid-release and sustained-release dual-effect tablets prepared in this example were dispersed with standard hard water, and the wetting time was 41 s. The average particle size of the nano-sized drug-carrying particles in the drug-carrying system was 76 nm, and the average particle size of the micro-sized drug-carrying particles was 2.6 microns.

[0084] Example 6: Preparation of 15% mass concentration of B2-type avermectin rapid-release and sustained-release dual-effect powder

[0085] The implementation steps of this embodiment are as follows:

[0086] (1) Weigh 1 g of polylactic acid and dissolve it in 8 mL of dichloromethane to obtain a transparent oil phase A after it is completely dissolved;

[0087] (2) 1.5 g of B2 avermectin technical, 0.5 g of Nongru 600 and 0.5 g of Nongru 700 were added to A and completely dissolved to obtain a transparent oil phase B;

[0088] (3) Slowly add the oil phase B dropwise into 15 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0089] (4) Add 6.5 g of sodium dodecyl sulfate (Shanghai MacLean Biochemical Technology Co., Ltd.) to the mixed phase C under stirring at 500 rpm to obtain a mixture D;

[0090] (5) The mixture D is heated in an oven at 45° C., and after the dichloromethane and water are completely volatilized, the mixture is pulverized again to obtain a B2 avermectin rapid-release and sustained-release dual-effect powder.

[0091] The B2-type avermectin rapid-release and sustained-release dual-effect powder prepared in this example was dispersed with standard hard water, and the wetting time was 33 seconds. The average particle size of the nano-scale drug-carrying particles in the drug-carrying system was 72 nm, and the average particle size of the micro-scale drug-carrying particles was 4.3 microns.

[0092] Example 7: Preparation of a dual-loaded rapid-release and sustained-release powder containing 2.5% B1-type avermectin and 2.5% avermectin benzoate

[0093] The implementation steps of this embodiment are as follows:

[0094] (1) Weigh 0.5 g of polylactic acid and dissolve it in 4 mL of dichloromethane to obtain a transparent oil phase A after complete dissolution;

[0095] (2) adding 0.25 g of B1 type avermectin technical drug, 0.25 g of avermectin benzoate technical drug and 2 g of polyvinyl alcohol to solution A, and obtaining a transparent oil phase B after complete dissolution;

[0096] (3) Slowly add the oil phase B dropwise into 10 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0097] (4) adding 7 g of lactose to the mixed phase C while stirring at 500 rpm to obtain a mixture D;

[0098] (5) The mixture D is heated in an oven at 50° C., and after the dichloromethane and water are completely volatilized, the mixture is pulverized again to obtain a rapid-release and sustained-release dual-effect powder containing type B1 avermectin and avermectin benzoate.

[0099] The B1-type avermectin and avermectin benzoate dual-loaded rapid-release and sustained-release dual-effect powder prepared in this example was dispersed with standard hard water, and the wetting time was 16 seconds. The average particle size of the nano-scale drug-loaded particles in the drug-loaded system was 65 nm, and the average particle size of the micron-scale drug-loaded particles was 3.7 microns.

[0100] Example 8, sustained release performance test:

[0101] A pure sustained-release preparation of type B1 avermectin with ethyl cellulose as a single carrier was prepared by the following method. The specific preparation process is as follows: (1) weighing 0.1 g of type B1 avermectin original drug and 2 g of ethyl cellulose and dissolving them in 5 mL of dichloromethane, stirring to completely dissolve them, and obtaining oil phase A; (2) preparing a polyvinyl alcohol aqueous solution with a mass concentration of 5%, adding 5.9 g of sodium dodecyl sulfate to 40 mL of the polyvinyl alcohol aqueous solution, stirring until completely dissolved, and obtaining aqueous phase B; (3) adding oil phase A to aqueous phase B at a stirring speed of 1500 rpm, continuing to stir until the dichloromethane is completely volatilized, filtering, washing, and drying to obtain a pure sustained-release preparation of type B1 avermectin-ethyl cellulose.

[0102] The sustained-release carrier polylactic acid in Example 1 was replaced with ethyl cellulose, and other components and contents were kept unchanged to prepare a dual-effect preparation with ethyl cellulose as a sustained-release carrier.

[0103] Take a certain amount of the B1 type avermectin quick-release-slow-release dual-effect powder prepared in Example 1, the dual-effect preparation with ethyl cellulose as the slow-release carrier, and the pure slow-release preparation of ethyl cellulose and put them into a dialysis bag, take 15% ethanol solution as the slow-release medium, and carry out the slow-release performance test in a constant temperature shaking table at 25°C. Take out 1mL of the slow-release solution at 5h, 10h, 24h, 48h, 72h, 96h and 120h after the slow release, respectively, adopt high performance liquid chromatography to measure the content of pesticide in the slow-release solution, and calculate the slow-release rate. After each sampling, 1mL of 15% ethanol solution is added again to supplement the slow-release medium.

[0104] In the experiment, the sustained release performance of the drug prepared by the present invention was compared with that of the preparation using ethyl cellulose as a single carrier. Figure 3 The test results show that the dual-effect solid pesticide preparation prepared by the preparation method of the present invention with polylactic acid as the sustained-release carrier and sodium benzoate as the rapid-release carrier, compared with the widely used ethyl cellulose as the single sustained-release carrier, exhibits a burst release characteristic in the early stage of release, has a faster release rate, and exhibits rapid-release performance. Subsequently, as the drug is slowly released in the sustained-release carrier, it presents a gentle release process, and the release rate is significantly lower than that of the control sustained-release preparation, which can effectively prolong the duration of the agent and save production costs.

[0105] In contrast, the release rate of pesticides in the dual-effect preparation prepared with ethyl cellulose as a sustained-release carrier is faster, and most of the drugs are released in a short time. The reason is that in this preparation method, ethyl cellulose cannot achieve a good coating of avermectin, and most of the active ingredients of the pesticide are only freely adsorbed on the carrier. After entering the solution, they are quickly dissolved and released, making it difficult to achieve an ideal controlled-release effect.

[0106] Example 9: Leaf surface adhesion retention performance test

[0107] The leaf retention was determined by the immersion method. Take fresh and clean cucumber and cabbage leaves, and measure their surface areas with a leaf area meter. Immerse the leaves in the aqueous dispersion of the B1-type avermectin rapid-release and sustained-release dual-effect powder prepared in Example 1 and the above-mentioned ethyl cellulose sustained-release preparation, respectively. After immersion for 15 seconds, take out the leaves and place them vertically until the droplets stop dripping. Record the mass of each leaf before and after immersion. Retention (Rm, mg / cm 2 The calculation formula of Rm is: Rm = (W1-W0) / S. Where: W0 and W1 are the weight of the leaf before and after immersion in the dispersion (mg), S is the leaf area (cm 2 ).

[0108] The test results are as follows Figure 4 As shown, the retention amount of the quick-release and sustained-release dual-effect solid pesticide prepared by the preparation method of the present invention on the hydrophilic cucumber and hydrophobic cabbage leaf surfaces is greater than that of the pure sustained-release preparation of ethyl cellulose, indicating that it has better leaf surface adhesion and retention performance, which is mainly attributed to the small size effect, large specific surface effect, interface effect and high permeability of the nanoparticles. The improvement of leaf surface adhesion and retention performance can increase the effective utilization rate of pesticides, reduce pesticide loss, reduce the dosage, and improve the environmental and ecological effects of the preparation.

[0109] Example 10, Biological Activity Assay

[0110] The biological test process is as follows: Use 0.05% Triton X-100 aqueous solution to dilute the B1 type avermectin rapid-release and sustained-release dual-effect powder prepared in Example 1 and the above-mentioned ethyl cellulose pure sustained-release preparation into a series of concentration solutions. Select cabbage leaves of appropriate size and immerse them in different concentrations of solutions. Take them out after 10 seconds. After drying at room temperature, place the leaves in a disposable culture dish covered with filter paper. Select 10 2nd instar larvae of diamondback moth from each dish, and repeat each treatment 4 times. Use 0.05% Triton X-100 aqueous solution as a blank control. The treated test insects are raised under normal feeding conditions. Check the number of dead and live insects after 24 hours and 72 hours, and calculate the mortality rate. Use DPS software to calculate the toxicity regression equation, LC 50 and correlation coefficient.

[0111] Table 1 Toxicity test results of different preparations to Plutella xylostella (24h)

[0112]

[0113] Table 2 Toxicity test results of different preparations to Plutella xylostella (72h)

[0114]

[0115] The test results are shown in Tables 1 and 2. The data show that the rapid-release and sustained-release dual-effect powder of the present invention has a higher LC value against Plutella xylostella than the conventional sustained-release powder, whether it is 24h or 72h. 50 The insecticidal effect is better in both rapid and long-term effects, and its dual-effect function is more excellent. The improvement of insecticidal activity can reduce the amount of pesticides used and improve the ecological safety and economic benefits of the preparation.

[0116] Comparative Example 1

[0117] (1) Weigh 2.0 g of polylactic acid and dissolve it in 15 mL of dichloromethane to obtain a transparent oil phase A after complete dissolution;

[0118] (2) 1.3 g of B1 type avermectin technical, 1.5 g of Nongru 600 and 1.5 g of Nongru 700 were added to A and completely dissolved to obtain a transparent oil phase B;

[0119] (3) Slowly add the oil phase B dropwise into 25 mL of water and shear at 5000 rpm to obtain a mixed phase C;

[0120] (4) adding 3.7 g of sodium benzoate to the mixed phase C while stirring at 500 rpm to obtain a mixture D;

[0121] (5) The mixture D is heated in an oven at 45° C., and after the dichloromethane and water are completely volatilized, the mixture is pulverized again to obtain a B1 type avermectin rapid-release and sustained-release dual-effect pesticide powder.

[0122] The prepared solid preparation, after being dispersed with standard hard water, had a wetting time of 87 seconds. The average particle size of the nano-sized drug-carrying particles in the drug-carrying system was measured by a Malvern particle size analyzer to be 335 nm, and the average particle size of the micro-sized drug-carrying particles was 5.1 microns. The dispersibility and uniformity of the preparation were significantly reduced.

[0123] Using 15% ethanol solution as the sustained-release medium, the sustained-release curve Figure 5 As shown. Because the content of the quick-release carrier that plays a role of barrier and rapid dispersion is reduced in the composition, the prepared solid particles are prone to agglomeration and adhesion, and most of the active ingredients of the pesticide are wrapped in the slow-release carrier, so the dispersibility and quick-release properties of the preparation are significantly reduced. At the same time, due to the presence of particle aggregates, the particles are also prone to collapse and sedimentation in the slow-release medium, so the rate of pesticide release is very slow, the active ingredients in the liquid are very low, and it is difficult to meet the needs of practical applications.

[0124] The present invention has been described in detail above. For those skilled in the art, without departing from the purpose and scope of the present invention, and without the need to carry out unnecessary experimental conditions, the present invention can be implemented in a wide range under equivalent parameters, concentrations and conditions. Although the present invention provides specific embodiments, it should be understood that the present invention can be further improved. In a word, according to the principles of the present invention, the application is intended to include any changes, uses or improvements to the present invention, including departure from the disclosed scope in the application, and changes made with conventional techniques known in the art.

Claims

1. Avermectin quick-release and sustained-release dual-effect solid pesticide, in parts by weight, has the following composition: Avermectin active ingredients 1%-20% Surfactant 1%-30% Sustained release carrier 0.5%-10% Immediate-release carrier 59.5%-90%; The sustained-release carrier is at least one of polylactic acid and polylactic acid-glycolic acid copolymer; The surfactant is: anionic surfactant, nonionic surfactant or a combination thereof; in, The anionic surfactant is selected from: maleic rosin polyoxyethylene-oxypropylene ether sulfonate and lignin sulfonate; The nonionic surfactant is selected from: polyoxyethylene styrylphenol ether, polyoxyethylene alkylphenol formaldehyde resin ether, polyvinyl alcohol; The rapid-release carrier is selected from the group consisting of sodium n-butyrate, sodium benzoate, sodium dodecyl sulfate, and lactose; The avermectin quick-release and sustained-release dual-effect solid pesticide is prepared by a method comprising the following steps: (1) dissolving the sustained-release carrier in an organic solvent to obtain a transparent oil phase A; (2) Adding avermectin active ingredients and surfactants into A, and dissolving them completely to obtain a uniformly dispersed transparent oil phase B; (3) Slowly add the oil phase B into the water and shear and emulsify to obtain the mixed phase C; (4) adding a quick-release carrier to C while stirring to obtain a mixture D; (5) The solvent and water in D are removed to obtain an avermectin-based rapid-release and sustained-release dual-effect solid pesticide.

2. The avermectin quick-release and sustained-release dual-effect solid pesticide according to claim 1, characterized in that: The avermectin active ingredient is selected from one or more of: type B1 avermectin, type B2 avermectin and avermectin benzoate.

3. The avermectin quick-release and sustained-release dual-effect solid pesticide according to claim 1, characterized in that: In step (1), the organic solvent is a low-boiling point organic solvent that can dissolve both the sustained-release carrier and the avermectin active ingredient and is immiscible with water.

4. The avermectin quick-release and sustained-release dual-effect solid pesticide according to claim 3, characterized in that: The organic solvent is at least one of dichloromethane and chloroform.

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