Water dispersible granule based on emamectin benzoate and abamectin and preparation process thereof

Abstract

The invention discloses water dispersible granules based on emamectin benzoate and abamectin and a preparation process of the water dispersible granules, and relates to the technical field of pharmacy, and the water dispersible granules are prepared from emamectin benzoate, abamectin, modified eucalyptus oil, a wetting agent, a disintegrating agent, a binder and filler in a weight ratio of (5-20): (3-15): (5-8): (4-10): (6-12): (3-7): (40-65). And reacting the modified eucalyptus oil with maleic anhydride to obtain an esterification product, and reacting the esterification product with methoxypolyethylene glycol to obtain the modified eucalyptus oil. The water dispersible granule is good in water solubility and high in dispersion uniformity, and the stability of the product is improved.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceuticals, and in particular to a water dispersible granule based on emamectin benzoate and avermectin and a preparation process thereof. Background Art

[0002] Emamectin benzoate and avermectin are both highly effective biogenic insecticides commonly used in agricultural production, and have excellent control effects on a variety of pests. However, the existing emamectin benzoate and avermectin compound preparations on the market, especially water-dispersible granules, have deficiencies in dispersibility, water solubility and stability. Poor dispersibility will result in the inability to disperse the agent evenly in water, affecting the consistency of the efficacy; poor water solubility will cause the agent to dissolve slowly, increasing the time cost of application; lack of stability will easily cause the degradation of the active ingredients and shorten the shelf life of the preparation, which needs to be improved urgently. Summary of the invention

[0003] The first technical problem to be solved by the present invention is: in view of the deficiencies in the prior art, a water-dispersible granule based on emamectin benzoate and avermectin is provided, which has good water solubility, dispersibility and stability.

[0004] To solve the above-mentioned first technical problem, the technical solution of the present invention is: A water dispersible granule based on emamectin benzoate and abamectin, comprising emamectin benzoate, abamectin, modified eucalyptus oil, a wetting agent, a disintegrant, a binder and a filler in a weight ratio of (5-20): (3-15): (5-8): (4-10): (6-12): (3-7): (40-65); The preparation method of the modified eucalyptus oil is: A. Add eucalyptus oil and maleic anhydride to a reactor, add p-toluenesulfonic acid as a catalyst, heat to 60-80°C, and react for 3-5h under nitrogen protection; B. After the reaction is completed, a sodium hydroxide solution with a concentration of 10-15%wt is added dropwise to the system until the pH value of the system reaches 7-8, and then an equal volume of deionized water is added to the reaction system, and the mixture is stirred for 15-20 minutes and then allowed to stand for stratification, the lower aqueous phase is removed, and the water washing operation is repeated 2-3 times to obtain an esterified product; C. Transfer the above esterification product to a reactor, then add polyethylene glycol monomethyl ether and potassium hydroxide as a catalyst, raise the temperature to 120-130° C., and react for 4-6 hours; D. After the reaction is completed, cool to room temperature, first adjust the pH value of the system to 6-7 with 10-15%wt dilute hydrochloric acid solution, and distill at 0.08-1.5 kPa and 80-120°C for 30-90 minutes to obtain the modified eucalyptus oil.

[0005] Preferably, in step A, the molar ratio of eucalyptus oil to maleic anhydride is 1:1-2, and the amount of p-toluenesulfonic acid added accounts for 0.5-1% of the total mass of the system; In step C, the average molecular weight of polyethylene glycol monomethyl ether is 400-600, the molar ratio of the esterification product to polyethylene glycol monomethyl ether is 1:1.2-1.5, and the amount of potassium hydroxide added accounts for 2-3% of the total mass of the system.

[0006] Preferably, the wetting agent is modified fatty alcohol polyoxyethylene ether, and the preparation method thereof is: At 0-5°C, add fatty alcohol polyoxyethylene ether to a reactor filled with glacial acetic acid, stir evenly, then drop chlorosulfonic acid, control the material temperature in the reactor not to exceed 5°C during the dropwise addition, and control the dropwise addition time to 30-45min. After the dropwise addition is completed, heat to 30-40°C and react for 2-3h; After the reaction is completed, the reaction product is poured into ice water for quenching, and then neutralized to pH 7-8 with a mass fraction of 10-15%wt sodium hydroxide solution, and then extracted with ether, the lower aqueous phase is collected, and distilled at 0.15-0.4 kPa and 30-60°C for 60-120min to obtain modified fatty alcohol polyoxyethylene ether.

[0007] Preferably, the molar ratio of fatty alcohol polyoxyethylene ether to chlorosulfonic acid is 1:1.1-1.3; Preferably, the amount of glacial acetic acid added is 2-3 times the volume of the fatty alcohol polyoxyethylene.

[0008] The disintegrant is modified white carbon black, and the modification method is as follows: Disperse white carbon black in deionized water to prepare a suspension with a mass fraction of 10-20%wt, place it in a reactor, stir it at a speed of 800-1000rpm, first dropwise add an aqueous solution of alkylphenol polyoxyethylene ether with a mass fraction of 20-30%wt, and continue stirring for 15-30min after the addition is completed; then dropwise add an aqueous solution of sodium dodecyl sulfate with a mass fraction of 15-25%wt, and stir for another 20-30min after the addition is completed; After the stirring is completed, suction filtration is performed, and the obtained filter cake is washed with deionized water for 2-3 times, and then dried at 50-70°C for 4-6 hours to obtain modified white carbon black.

[0009] Preferably, the mass ratio of white carbon black to alkylphenol polyoxyethylene ether and sodium lauryl sulfate is 100:5-10:3-8.

[0010] Preferably, the preparation method of the binder is: Anhydrous ethanol is added to the reaction kettle, stirring is started, and then refined corn starch and sodium hydroxide are added in sequence, the stirring speed is controlled at 300-500 rpm, and stirring is continued for 15-30 minutes to obtain a starch suspension.

[0011] Ethylene oxide was introduced into the reactor, and the temperature in the reactor was controlled at 50-70°C for 3-5 hours; After the reaction is completed, the reaction product is transferred to a neutralization kettle, and dilute hydrochloric acid with a concentration of 10-15%wt is added until the pH value of the system reaches 6-7, and then the reaction product is washed with deionized water 3-4 times. Finally, the reaction product is dried at 50-70°C and 0.08-0.09MPa for 3-5h to obtain the binder.

[0012] Preferably, the moisture content of the refined corn starch is less than 15% and the particle size is 60-80 mesh; The mass ratio of refined corn starch, ethylene oxide, sodium hydroxide and anhydrous ethanol is 100:20-30:1-3:200-300.

[0013] Preferably, the filler comprises sodium carboxymethyl cellulose and diatomaceous earth, and the mass ratio of sodium carboxymethyl cellulose to diatomaceous earth is 1:5-7.

[0014] The second technical problem to be solved by the present invention is: in view of the deficiencies in the prior art, a water-dispersible granule based on emamectin benzoate and avermectin is provided, which has good water solubility, dispersibility and stability.

[0015] To solve the above second technical problem, the technical solution of the present invention is: A preparation process of water dispersible granules based on emamectin benzoate and avermectin comprises the following steps: First, put emamectin benzoate, avermectin and modified eucalyptus oil into a high-speed mixer and stir at 100-180 rpm for 3-5 minutes to make them preliminarily mixed evenly; then add a wetting agent, increase the stirring speed to 800-1000 rpm, stir for 8-12 minutes to obtain a mixture; Continue to add disintegrant, binder and filler to the mixture, spray deionized water at the same time, control the material humidity at 25-35%, start the kneading machine to knead for 15-20 minutes, and then use the extrusion granulator to granulate into columnar particles with a particle size of 1-3 mm; The prepared granules are placed in a fluidized bed dryer, the temperature is controlled at 40-60°C, and dried until the moisture content is less than 3% to obtain water dispersible granules.

[0016] Due to the adoption of the above technical solution, the beneficial effects of the present invention are: 1. Through the esterification reaction between maleic anhydride and eucalyptus oil, polar anhydride groups are introduced into the original non-polar molecular structure of eucalyptus oil. The increase of polar groups initially changes the polarity of the molecule, improving its hydrophilicity. The access of polyethylene glycol monomethyl ether adds a hydrophilic ether chain structure to the eucalyptus oil derivative, greatly improving its water solubility. In the aqueous system, the interaction between the modified eucalyptus oil and water molecules is enhanced, making it easier to disperse in water, reducing the interfacial tension with water, and the new molecular structure helps to break the original cohesion of water, making the system more stable and uniform. The water-dispersible granules can be better suspended and dispersed in water, reducing agglomeration and precipitation. The modified eucalyptus oil acts as a cosolvent to help the active ingredients of the insecticide to be better dispersed in the aqueous phase, forming a uniform and stable dispersion system, so that the target area can be more evenly covered when the agent is sprayed, avoiding excessive or low local concentrations, and improving the insecticidal effect.

[0017] 2. After the modified eucalyptus oil is dissolved in water, it contains a variety of natural active ingredients such as eucalyptol, which play a synergistic role in the use of emamectin benzoate and avermectin. On the one hand, it can interfere with the nervous system and respiratory system of pests, making pests more sensitive to pesticides, reducing their resistance, and increasing the efficacy of emamectin benzoate and avermectin; on the other hand, it can act on the epidermis of pests, destroy their wax layer, help pesticides penetrate, and then enhance the insecticidal effect and reduce the amount of pesticides used. In addition, eucalyptus oil has antioxidant properties, which can improve the overall stability of water-dispersible granules. Its special smell can attract pests to the application area, increase the probability of pests contacting pesticides, and allow the pesticides to act accurately on target pests, avoiding waste of pesticides and improving prevention and control efficiency.

[0018] 3. Sulfonation modification of fatty alcohol polyoxyethylene ether gives fatty alcohol polyoxyethylene ether stronger hydrophilicity, improves its dispersion and wetting effect in aqueous system. After modification, the wetting time of fatty alcohol polyoxyethylene ether is greatly shortened. In the pesticide particle dispersion system, the dispersion uniformity is improved, which can quickly make the material evenly dispersed and spread, and improve its stability.

[0019] 4. By successively coating the two surfactants, alkylphenol polyoxyethylene ether and sodium dodecyl sulfate, on the surface of silica, its surface energy is reduced, hydrophilicity is enhanced, liquid-solid interfacial tension is reduced, and water penetration into the particles is accelerated, which greatly optimizes the quality of the preparation. At the same time, sodium dodecyl sulfate has a wetting effect and can cooperate with modified silica to promote the rapid disintegration and dissolution of water-dispersible granules. The suspension rate is greatly improved compared with the unmodified state, and the dispersion time and disintegration time are shortened.

[0020] 5. By modifying refined corn starch, ethylene oxide reacts with the hydroxyl groups on the starch molecules to undergo etherification reaction, and hydroxyethyl groups are gradually added to the starch chains. The hydrophilicity of the modified starch ether is significantly enhanced, and the cold water solubility is greatly improved. It can quickly dissolve at room temperature to form a stable and transparent solution, and the gelatinization temperature is significantly reduced, which effectively avoids the problem of high-temperature energy consumption during traditional starch gelatinization. The gelatinized solution has enhanced anti-aging ability, and is not prone to precipitation and stratification after long-term storage, which meets the dual requirements of water-dispersible granules for the binder to be quickly soluble in water and to be able to form a stable shape.

[0021] 6. The porous structure of diatomaceous earth and the swelling and bonding properties of sodium carboxymethyl cellulose work together to ensure that the water-dispersible granules have sufficient mechanical strength during storage and transportation, and will not break easily. When in use, water can quickly penetrate into the granules to achieve more balanced disintegration and dispersion, thereby improving the quality of the product. DETAILED DESCRIPTION

[0022] The present invention will be further described below in conjunction with the embodiments.

[0023] Example 1 A preparation process of water dispersible granules based on emamectin benzoate and avermectin comprises the following steps: First, put emamectin benzoate, avermectin and modified eucalyptus oil into a high-speed mixer and stir at 100-180 rpm for 3-5 minutes to make them preliminarily mixed evenly; then add a wetting agent, increase the stirring speed to 800-1000 rpm, stir for 8-12 minutes to obtain a mixture; Continue to add disintegrant, binder and filler to the mixture, spray deionized water at the same time, control the material humidity at 25-35%, start the kneading machine to knead for 15-20 minutes, and then use the extrusion granulator to granulate into columnar particles with a particle size of 1-3 mm; The prepared granules are placed in a fluidized bed dryer, the temperature is controlled at 40-60°C, and dried until the moisture content is less than 3% to obtain water dispersible granules.

[0024] Example 2 Prepared according to the method of Example 1, the mass fractions of the components in the water dispersible granules are: Emamectin benzoate: 5% Avermectin: 3% Modified eucalyptus oil: 5% Wetting agent (modified fatty alcohol polyoxyethylene ether): 4% Disintegrant (modified silica): 6% Binder: 3% Filler (sodium carboxymethyl cellulose: diatomaceous earth = 1:5): 74% Preparation steps: Preparation of modified eucalyptus oil: Take appropriate amounts of eucalyptus oil and maleic anhydride to make a molar ratio of 1:1, add 0.5% of p-toluenesulfonic acid as a catalyst, heat to 60°C, and react for 3 hours under nitrogen protection.

[0025] After the reaction, a 10% wt sodium hydroxide solution was slowly added dropwise to the system to neutralize the unreacted anhydride until the pH value of the system reached 7. Subsequently, an equal volume of deionized water was added to the reaction system, and the mixture was stirred for 15 min and allowed to stand for stratification. The lower aqueous phase was removed and the water washing operation was repeated twice to obtain the esterification product.

[0026] The above esterification product was transferred to a reactor, and polyethylene glycol monomethyl ether with an average molecular weight of 400 was added to make the molar ratio of the esterification product to polyethylene glycol monomethyl ether 1:1.2. At the same time, potassium hydroxide accounting for 2% of the total mass of the system was added as a catalyst, the temperature was raised to 120°C, and the reaction was carried out for 4 hours.

[0027] After the reaction was completed, the mixture was cooled to room temperature, the pH value of the system was adjusted to 6 with a 10% wt dilute hydrochloric acid solution, and distilled at 0.08 kPa and 80°C for 30 min to obtain modified eucalyptus oil.

[0028] Preparation of modified fatty alcohol polyoxyethylene ether: At 0°C, add an appropriate amount of fatty alcohol polyoxyethylene ether into a reactor filled with glacial acetic acid (the amount of glacial acetic acid added is twice the volume of fatty alcohol polyoxyethylene), stir evenly, then add chlorosulfonic acid dropwise to make the molar ratio of fatty alcohol polyoxyethylene ether to chlorosulfonic acid be 1:1.1. During the addition, control the material temperature in the reactor not to exceed 5°C, and control the addition time to 30min. After the addition is completed, heat to 30°C and react for 2h.

[0029] After the reaction is completed, the reaction product is poured into ice water for quenching, and then neutralized to pH 7 with a mass fraction of 10% wt sodium hydroxide solution, and then extracted with ether, the lower aqueous phase is collected, and distilled at 0.15 kPa and 30°C for 60 minutes to obtain modified fatty alcohol polyoxyethylene ether.

[0030] Preparation of modified silica: Disperse white carbon black in deionized water to prepare a suspension with a mass fraction of 10% wt, place it in a reactor, stir it at a speed of 800 rpm, first add a 20% wt aqueous solution of alkylphenol polyoxyethylene ether to make the mass ratio of white carbon black to alkylphenol polyoxyethylene ether and sodium dodecyl sulfate be 100:5:3, and continue stirring for 15 minutes after the addition is completed; then add a 15% wt aqueous solution of sodium dodecyl sulfate to the reactor, and stir for 20 minutes after the addition is completed.

[0031] After the stirring was completed, suction filtration was performed, and the filter cake was washed twice with deionized water and then dried at 50° C. for 4 h to obtain modified silica.

[0032] Preparation of binder: Add anhydrous ethanol into the reaction kettle, start stirring, and then add refined corn starch with a moisture content of less than 15% and a particle size of 60-80 mesh and sodium hydroxide in sequence. The mass ratio of refined corn starch, ethylene oxide, sodium hydroxide, and anhydrous ethanol is 100:20:1:200. Control the stirring speed at 300 rpm and continue stirring for 15 minutes to obtain a starch suspension.

[0033] Ethylene oxide was introduced into the reactor and the temperature in the reactor was controlled at 50°C for 3 h.

[0034] After the reaction was completed, the reaction product was transferred to a neutralization kettle, and 10% wt dilute hydrochloric acid was added until the pH value of the system reached 6. The reaction product was then washed three times with deionized water. Finally, the reaction product was dried at 50°C and a vacuum degree of 0.08 MPa for 3 h to obtain a binder.

[0035] Example 3 Prepared according to the method of Example 1, the mass fractions of the components in the water dispersible granules are: Raw material weight ratio: Emamectin benzoate: 10% Avermectin: 8% Modified eucalyptus oil: 6% Wetting agent (modified fatty alcohol polyoxyethylene ether): 7% Disintegrant (modified silica): 8% Binder: 5% Filler (sodium carboxymethyl cellulose: diatomaceous earth = 1:6): 56% Preparation steps: Preparation of modified eucalyptus oil: Take appropriate amounts of eucalyptus oil and maleic anhydride to make a molar ratio of 1:1.5, add 0.7% of p-toluenesulfonic acid as a catalyst, heat to 70°C, and react for 4 hours under nitrogen protection.

[0036] After the reaction, a 12% wt sodium hydroxide solution was slowly added dropwise to the system to neutralize the unreacted anhydride until the pH value of the system reached 7.5. Subsequently, an equal volume of deionized water was added to the reaction system, and the mixture was stirred for 18 min and allowed to stand for stratification. The lower aqueous phase was removed and the water washing operation was repeated twice to obtain the esterification product.

[0037] The above esterification product was transferred to a reactor, and polyethylene glycol monomethyl ether with an average molecular weight of 500 was added to make the molar ratio of the esterification product to polyethylene glycol monomethyl ether 1:1.3. At the same time, potassium hydroxide accounting for 2.5% of the total mass of the system was added as a catalyst, the temperature was raised to 125°C, and the reaction was carried out for 5 hours.

[0038] After the reaction was completed, the mixture was cooled to room temperature, the pH value of the system was adjusted to 6.5 with a 12% wt dilute hydrochloric acid solution, and distilled at 0.8 kPa and 100° C. for 60 min to obtain modified eucalyptus oil.

[0039] Preparation of modified fatty alcohol polyoxyethylene ether: At 2°C, add an appropriate amount of fatty alcohol polyoxyethylene ether into a reactor filled with glacial acetic acid (the amount of glacial acetic acid added is 2.5 times the volume of fatty alcohol polyoxyethylene). After stirring evenly, add chlorosulfonic acid dropwise to make the molar ratio of fatty alcohol polyoxyethylene ether to chlorosulfonic acid be 1:1.2. During the addition, control the material temperature in the reactor not to exceed 5°C, and control the addition time to 38min. After the addition is completed, raise the temperature to 35°C and react for 2.5h.

[0040] After the reaction is completed, the reaction product is poured into ice water for quenching, and then neutralized to pH 7.5 with a sodium hydroxide solution with a mass fraction of 12% wt, and then extracted with ether, the lower aqueous phase is collected, and distilled at 0.3 kPa and 45°C for 90 minutes to obtain modified fatty alcohol polyoxyethylene ether.

[0041] Preparation of modified silica: Disperse white carbon black in deionized water to prepare a suspension with a mass fraction of 15% wt, place it in a reactor, and stir it at a speed of 900 rpm. First, add a 25% wt aqueous solution of alkylphenol polyoxyethylene ether to make the mass ratio of white carbon black to alkylphenol polyoxyethylene ether and sodium dodecyl sulfate be 100:8:5. After the addition is completed, continue stirring for 23 minutes; then add a 20% wt aqueous solution of sodium dodecyl sulfate to the reactor, and stir for another 25 minutes after the addition is completed.

[0042] After the stirring was completed, suction filtration was performed, and the filter cake was washed three times with deionized water and then dried at 60° C. for 5 h to obtain modified silica.

[0043] Preparation of binder: Add anhydrous ethanol into the reaction kettle, start stirring, and then add refined corn starch with a moisture content of less than 15% and a particle size of 60-80 mesh and sodium hydroxide in sequence. The mass ratio of refined corn starch, ethylene oxide, sodium hydroxide, and anhydrous ethanol is 100:25:2:250. Control the stirring speed at 400 rpm and continue stirring for 23 minutes to obtain a starch suspension.

[0044] Ethylene oxide was introduced into the reactor and the temperature in the reactor was controlled at 60°C for 4 hours.

[0045] After the reaction was completed, the reaction product was transferred to a neutralization kettle, and dilute hydrochloric acid with a concentration of 12% wt was added until the pH value of the system reached 6.5, and then the reaction product was washed with deionized water for 3 times. Finally, the reaction product was dried at 60°C and a vacuum degree of 0.085 MPa for 4 hours to obtain a binder.

[0046] Example 4 Prepared according to the method of Example 1, the mass fractions of the components in the water dispersible granules are: Raw material weight ratio: Emamectin benzoate: 15% Avermectin: 12% Modified eucalyptus oil: 7% Wetting agent (modified fatty alcohol polyoxyethylene ether): 9% Disintegrant (modified silica): 10% Binder: 6% Filler (sodium carboxymethyl cellulose: diatomaceous earth = 1:6.5): 41% Preparation steps: Preparation of modified eucalyptus oil: Take appropriate amounts of eucalyptus oil and maleic anhydride to make the molar ratio of the two to be 1:1.8, add 0.9% of the total mass of p-toluenesulfonic acid as a catalyst, heat to 75°C, and react for 4.5 hours under nitrogen protection.

[0047] After the reaction is completed, a 13% wt sodium hydroxide solution is slowly added into the system to neutralize the unreacted anhydride until the pH value of the system reaches 7.2. Subsequently, deionized water of an equal volume to the reaction system is added, and the mixture is stirred for 16 min and allowed to stand for stratification. The lower aqueous phase is removed, and the water washing operation is repeated 3 times to obtain the esterification product.

[0048] The above esterification product was transferred to a reactor, and polyethylene glycol monomethyl ether with an average molecular weight of 550 was added to make the molar ratio of the esterification product to polyethylene glycol monomethyl ether 1:1.4. At the same time, potassium hydroxide accounting for 2.8% of the total mass of the system was added as a catalyst, the temperature was raised to 128°C, and the reaction was carried out for 5.5 hours.

[0049] After the reaction was completed, the mixture was cooled to room temperature, the pH value of the system was adjusted to 6.2 with a 13% wt dilute hydrochloric acid solution, and distilled at 1.2 kPa and 110° C. for 80 min to obtain modified eucalyptus oil.

[0050] Preparation of modified fatty alcohol polyoxyethylene ether: At 4°C, add an appropriate amount of fatty alcohol polyoxyethylene ether into a reactor filled with glacial acetic acid (the amount of glacial acetic acid added is 2.8 times the volume of fatty alcohol polyoxyethylene). After stirring evenly, add chlorosulfonic acid dropwise to make the molar ratio of fatty alcohol polyoxyethylene ether to chlorosulfonic acid be 1:1.25. During the addition, control the material temperature in the reactor not to exceed 5°C, and control the addition time to 40min. After the addition is completed, raise the temperature to 38°C and react for 2.8h.

[0051] After the reaction is completed, the reaction product is poured into ice water for quenching, and then neutralized to pH 7.2 with a sodium hydroxide solution with a mass fraction of 13% wt, and then extracted with ether, the lower aqueous phase is collected, and distilled at 0.35 kPa and 50°C for 100 minutes to obtain modified fatty alcohol polyoxyethylene ether.

[0052] Preparation of modified silica: Disperse white carbon black in deionized water to prepare a suspension with a mass fraction of 18% wt, place it in a reactor, and stir it at a speed of 950 rpm. First, add a 28% wt aqueous solution of alkylphenol polyoxyethylene ether to make the mass ratio of white carbon black to alkylphenol polyoxyethylene ether and sodium dodecyl sulfate be 100:9:6. After the addition is completed, continue stirring for 28 minutes; then add a 22% wt aqueous solution of sodium dodecyl sulfate to the reactor, and stir for another 28 minutes after the addition is completed.

[0053] After stirring, suction filtration was performed, and the filter cake was washed three times with deionized water and then dried at 65° C. for 5.5 h to obtain modified silica.

[0054] Preparation of binder: Add anhydrous ethanol into the reactor, start stirring, and then add refined corn starch with a moisture content of less than 15% and a particle size of 60-80 mesh and sodium hydroxide in sequence. The mass ratio of refined corn starch, ethylene oxide, sodium hydroxide and anhydrous ethanol is 100:28:2.5:280. Control the stirring speed at 450 rpm and continue stirring for 25 minutes to obtain a starch suspension.

[0055] Ethylene oxide was introduced into the reactor and the temperature in the reactor was controlled at 65°C for 4.5 hours.

[0056] After the reaction was completed, the reaction product was transferred to a neutralization kettle, and dilute hydrochloric acid with a concentration of 13% wt was added until the pH value of the system reached 6.2. The reaction product was then washed with deionized water for 4 times. Finally, the reaction product was dried at 65°C and a vacuum degree of 0.088 MPa for 4.5 hours to obtain a binder.

[0057] Example 5 Prepared according to the method of Example 1, the mass fractions of the components in the water dispersible granules are: Raw material weight ratio: Emamectin benzoate: 20% Avermectin: 15% Modified eucalyptus oil: 8% Wetting agent (modified fatty alcohol polyoxyethylene ether): 10% Disintegrant (modified silica): 12% Binder: 7% Filler (sodium carboxymethyl cellulose: diatomaceous earth = 1:7): ​​28% Preparation steps: Preparation of modified eucalyptus oil: Take appropriate amounts of eucalyptus oil and maleic anhydride to make a molar ratio of 1:2, add 1% of the total mass of the system p-toluenesulfonic acid as a catalyst, heat to 80°C, and react for 5 hours under nitrogen protection.

[0058] After the reaction, a 15% wt sodium hydroxide solution was slowly added dropwise to the system to neutralize the unreacted anhydride until the pH value of the system reached 8. Subsequently, an equal volume of deionized water was added to the reaction system, and the mixture was stirred for 20 min and allowed to stand for stratification. The lower aqueous phase was removed and the water washing operation was repeated 3 times to obtain the esterification product.

[0059] The above esterification product was transferred to a reactor, and polyethylene glycol monomethyl ether with an average molecular weight of 600 was added to make the molar ratio of the esterification product to polyethylene glycol monomethyl ether 1:1.5. At the same time, potassium hydroxide accounting for 3% of the total mass of the system was added as a catalyst, the temperature was raised to 130°C, and the reaction was carried out for 6 hours.

[0060] After the reaction was completed, the mixture was cooled to room temperature, the pH value of the system was adjusted to 7 with a 15% wt dilute hydrochloric acid solution, and distilled at 1.5 kPa and 120° C. for 90 min to obtain modified eucalyptus oil.

[0061] Preparation of modified fatty alcohol polyoxyethylene ether: At 5°C, add an appropriate amount of fatty alcohol polyoxyethylene ether into a reactor filled with glacial acetic acid (the amount of glacial acetic acid added is 3 times the volume of fatty alcohol polyoxyethylene). After stirring evenly, add chlorosulfonic acid dropwise to make the molar ratio of fatty alcohol polyoxyethylene ether to chlorosulfonic acid be 1:1.3. During the addition, control the material temperature in the reactor not to exceed 5°C, and control the addition time to 45min. After the addition is completed, raise the temperature to 40°C and react for 3h.

[0062] After the reaction is completed, the reaction product is poured into ice water for quenching, and then neutralized to pH 8 with a mass fraction of 15% wt sodium hydroxide solution, and then extracted with ether, the lower aqueous phase is collected, and distilled at 0.4 kPa and 60°C for 120 min to obtain modified fatty alcohol polyoxyethylene ether.

[0063] Preparation of modified silica: Disperse white carbon black in deionized water to prepare a suspension with a mass fraction of 20% wt, place it in a reactor, stir it at a speed of 1000 rpm, first add a 30% wt aqueous solution of alkylphenol polyoxyethylene ether to make the mass ratio of white carbon black to alkylphenol polyoxyethylene ether and sodium dodecyl sulfate be 100:10:8, and continue stirring for 30 minutes after the addition is completed; then add a 25% wt aqueous solution of sodium dodecyl sulfate to the solution, and stir for another 30 minutes after the addition is completed.

[0064] After the stirring was completed, suction filtration was performed, and the filter cake was washed three times with deionized water and then dried at 70° C. for 6 h to obtain modified silica.

[0065] Preparation of binder: Add anhydrous ethanol into the reaction kettle, start stirring, and then add refined corn starch with a moisture content of less than 15% and a particle size of 60-80 mesh and sodium hydroxide in sequence. The mass ratio of refined corn starch, ethylene oxide, sodium hydroxide and anhydrous ethanol is 100:30:3:300. Control the stirring speed at 500 rpm and continue stirring for 30 minutes to obtain a starch suspension.

[0066] Ethylene oxide was introduced into the reactor and the temperature in the reactor was controlled at 70°C for 5 hours.

[0067] After the reaction was completed, the reaction product was transferred to a neutralization kettle, and dilute hydrochloric acid with a concentration of 15% wt was added until the pH value of the system reached 7, and then the reaction product was washed 4 times with deionized water. Finally, the reaction product was subjected to the conditions of 70°C and a vacuum degree of 0.09 MPa to obtain a binder.

[0068] Comparative Example 1 The eucalyptus oil was not modified, and the rest was exactly the same as in Example 5.

[0069] Comparative Example 2 The fatty alcohol polyoxyethylene ether was not modified, and the rest was exactly the same as in Example 5.

[0070] Comparative Example 3 The white carbon black was not modified, and the rest was exactly the same as in Example 5.

[0071] Comparative Example 4 Only alkylphenol polyoxyethylene ether is used to modify white carbon black, and the rest is exactly the same as in Example 5.

[0072] Comparative Example 5 Only sodium dodecyl sulfate was used to modify the silica, and the rest was exactly the same as in Example 5.

[0073] Comparative Example 6 The binder used was refined corn starch without etherification modification, and the rest was exactly the same as in Example 5.

[0074] Comparative Example 7 Only sodium carboxymethyl cellulose was used as filler, and the rest was exactly the same as in Example 5.

[0075] Comparative Example 8 The filler used was diatomaceous earth, and the rest was exactly the same as in Example 5.

[0076] The performance of the water dispersible granules based on emamectin benzoate and avermectin in Examples 2-5 and Comparative Examples 1-8 was tested, and the results are shown in the following table: Table 1

[0077] Among them, stability is evaluated by storing the preparation at 40°C for one month and observing the retention rate of the active ingredient. "Relatively stable", "stable", "very stable" and "highly stable" indicate that the retention rate of the active ingredient is high and the quality of the preparation is stable; "slightly less stable", "average" and "poor" indicate that the active ingredient of the preparation has different degrees of loss or quality changes during storage.

[0078] Dispersion uniformity: Observe the dispersion of particles in the solution from the macro and micro perspectives. "Relatively uniform", "uniform" and "highly uniform" indicate good dispersion and less agglomeration; "average uniformity" indicates varying degrees of agglomeration or precipitation; and "uneven" indicates poor dispersion and a large amount of agglomeration or precipitation.

[0079] Dispersion time: record the time from putting the water-dispersible granules into water to forming a relatively uniform dispersion system. The shorter the time, the better the dispersion performance.

[0080] Suspension rate: refers to the proportion of active ingredients suspended in the solution after the preparation forms a suspension in water. The higher the value, the better.

[0081] Disintegration time: record the time required for the water-dispersible granules to disintegrate into small particles or disperse completely in water. The shorter the better.

[0082] Efficacy: Through indoor bioassay, with untreated pests and diseases as the control, the control effect of using the preparation is calculated. The higher the value, the better the efficacy. The above experimental data is based on the killing effect of Plutella xylostella.

[0083] It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope limited by the appended claims of the application.

Claims

1. A water dispersible granule based on emamectin benzoate and avermectin, characterized in that: The invention comprises emamectin benzoate, avermectin, modified eucalyptus oil, a wetting agent, a disintegrant, a binder and a filler in a weight ratio of (5-20): (3-15): (5-8): (4-10): (6-12): (3-7): (40-65); The preparation method of the modified eucalyptus oil is: A. Add eucalyptus oil and maleic anhydride to a reactor, add p-toluenesulfonic acid as a catalyst, heat to 60-80°C, and react for 3-5h under nitrogen protection; B. After the reaction is completed, a sodium hydroxide solution with a concentration of 10-15%wt is added dropwise to the system until the pH value of the system reaches 7-8, and then an equal volume of deionized water is added to the reaction system, and the mixture is stirred for 15-20 minutes and then allowed to stand for stratification, the lower aqueous phase is removed, and the water washing operation is repeated 2-3 times to obtain an esterified product; C. Transfer the above esterification product to a reactor, then add polyethylene glycol monomethyl ether and potassium hydroxide as a catalyst, raise the temperature to 120-130° C., and react for 4-6 hours; D. After the reaction is completed, cool to room temperature, first adjust the pH value of the system to 6-7 with 10-15%wt dilute hydrochloric acid solution, and distill at 0.08-1.5 kPa and 80-120°C for 30-90 minutes to obtain the modified eucalyptus oil.

2. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 1, characterized in that: In step A, the molar ratio of eucalyptus oil to maleic anhydride is 1:1-2, and the amount of p-toluenesulfonic acid added accounts for 0.5-1% of the total mass of the system; In step C, the average molecular weight of polyethylene glycol monomethyl ether is 400-600, the molar ratio of the esterification product to polyethylene glycol monomethyl ether is 1:1.2-1.5, and the amount of potassium hydroxide added accounts for 2-3% of the total mass of the system.

3. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 1, characterized in that: The wetting agent is modified fatty alcohol polyoxyethylene ether, and its preparation method is as follows: At 0-5°C, add fatty alcohol polyoxyethylene ether to a reactor filled with glacial acetic acid, stir evenly, then drop chlorosulfonic acid, control the material temperature in the reactor not to exceed 5°C during the dropwise addition, and control the dropwise addition time to 30-45min. After the dropwise addition is completed, heat to 30-40°C and react for 2-3h; After the reaction is completed, the reaction product is poured into ice water for quenching, and then neutralized to pH 7-8 with a mass fraction of 10-15%wt sodium hydroxide solution, and then extracted with ether, the lower aqueous phase is collected, and distilled at 0.15-0.4 kPa and 30-60°C for 60-120min to obtain modified fatty alcohol polyoxyethylene ether.

4. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 3, characterized in that: The molar ratio of fatty alcohol polyoxyethylene ether to chlorosulfonic acid is 1:1.1-1.3; The amount of glacial acetic acid added is 2-3 times the volume of the fatty alcohol polyoxyethylene.

5. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 1, characterized in that: The disintegrant is modified white carbon black, and the modification method is as follows: Disperse white carbon black in deionized water to prepare a suspension with a mass fraction of 10-20%wt, place it in a reactor, stir it at a speed of 800-1000rpm, first dropwise add an aqueous solution of alkylphenol polyoxyethylene ether with a mass fraction of 20-30%wt, and continue stirring for 15-30min after the addition is completed; then dropwise add an aqueous solution of sodium dodecyl sulfate with a mass fraction of 15-25%wt, and stir for another 20-30min after the addition is completed; After the stirring is completed, suction filtration is performed, and the obtained filter cake is washed with deionized water for 2-3 times, and then dried at 50-70°C for 4-6 hours to obtain modified white carbon black.

6. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 5, characterized in that: The mass ratio of white carbon black to alkylphenol polyoxyethylene ether and sodium dodecyl sulfate is 100:5-10:3-8.

7. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 1, characterized in that: The preparation method of the binder is: Anhydrous ethanol is added to the reaction kettle, stirring is started, and then refined corn starch and sodium hydroxide are added in sequence, the stirring speed is controlled at 300-500 rpm, and stirring is continued for 15-30 minutes to obtain a starch suspension; Ethylene oxide was introduced into the reactor, and the temperature in the reactor was controlled at 50-70°C for 3-5 hours; After the reaction is completed, the reaction product is transferred to a neutralization kettle, and dilute hydrochloric acid with a concentration of 10-15%wt is added until the pH value of the system reaches 6-7, and then the reaction product is washed with deionized water 3-4 times. Finally, the reaction product is dried at 50-70°C and 0.08-0.09MPa for 3-5h to obtain the binder.

8. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 7, characterized in that: The moisture content of refined corn starch is less than 15%, and the particle size is 60-80 mesh; The mass ratio of refined corn starch, ethylene oxide, sodium hydroxide and anhydrous ethanol is 100:20-30:1-3:200-300.

9. A water dispersible granule based on emamectin benzoate and avermectin as claimed in claim 1, characterized in that: The filler comprises sodium carboxymethyl cellulose and diatomaceous earth, and the mass ratio of sodium carboxymethyl cellulose to diatomaceous earth is 1:5-7.

10. The process for preparing water dispersible granules based on emamectin benzoate and avermectin according to any one of claims 1 to 9, characterized in that: The following steps are involved: First, put emamectin benzoate, avermectin and modified eucalyptus oil into a high-speed mixer and stir at 100-180 rpm for 3-5 minutes to make them preliminarily mixed evenly; then add a wetting agent, increase the stirring speed to 800-1000 rpm, stir for 8-12 minutes to obtain a mixture; Continue to add disintegrant, binder and filler to the mixture, spray deionized water at the same time, control the material humidity at 25-35%, start the kneading machine to knead for 15-20 minutes, and then use the extrusion granulator to granulate into columnar particles with a particle size of 1-3 mm; The prepared granules are placed in a fluidized bed dryer, the temperature is controlled at 40-60°C, and dried until the moisture content is less than 3% to obtain water dispersible granules.

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