LU501696B1

LU501696B1 - Azoxystrobin aqueous nanosuspension and preparation method thereof

Info

Publication number: LU501696B1
Application number: LU501696A
Authority: LU
Inventors: Tianqian Lei; Decang Liu; Shun Wang; Meirong Song; Hongjin Li
Original assignee: Univ Henan Agricultural
Priority date: 2022-03-23
Filing date: 2022-03-23
Publication date: 2022-09-23

Abstract

The present disclosure relates to an Azoxystrobin aqueous nanosuspension, which includes components in percentage by mass: 10%-20% of Azoxystrobin, 10%-30% of hydrophobic dispersible nanosilicon dioxide, 2%-10% of wetting dispersant, 0.2%-3% of thickener, 1%-5% of antifreezing agent, 0.01%-0.2% of preservative, and the balance of water. It has the following advantages of small grain diameter, high liquidity, and strengthening in permeability and conductivity in leaves; as surface energy is increased, it is easier to adsorb to plants; with strengthening in wind and rainwash resistance, pesticide residues flowing in soil may be reduced; and it achieves controlled-release effect, which fulfills objectives of improving effect and prolonging lasting validity period.

Description

AZOXYSTROBIN AQUEOUS NANOSUSPENSION AND PREPARATION METHOD !/501696

THEREOF TECHNICAL FIELD

[01] The present disclosure relates to an aqueous nanosuspension, in particular to an azoxystrobin aqueous nanosuspension and its preparation method.

BACKGROUND ART

[02] In recent years, nanotechnology has been widely applied in materials, manufacturing, and other fields, which has brought a profound change of human life. Generally, in the field of drug products, a nanoscale is defined within 1 nm to 1,000 nm. For a nano-drug product, particles of a drug or the drug is adsorbed and wrapped in a carrier to prepare nanoscale particles, and then, the nanoscale particles are prepared into different dosage forms. As the nano-drug product has a unique small-size effect, a surface effect, and other properties, it shows many excellent properties and new functions, which achieves a low cost, a high efficiency, an automation, and a large scale in a drug production; The drug will achieve an organ targeting, which has a wide application prospect in the use of clinical use. A preparation of the drug product with the nanotechnology will be an important development direction in the field of the drug products in future.

[03] Azoxystrobin is a new beta-methoxyacrylate bactericide synthesized by a natural antibiotic of a mushroom as a template under an artificial biomimetic with low toxicity, which possesses the effects of protection, treatment, and eradication. It can prevent an energy synthesis of pathogenic bacteria by inhibiting a respiratory action of the pathogenic bacteria. It has a high bactericidal activity, and can prevent and control majority of plant diseases, such as downy mildew, early blight, leaf spot disease, anthracnose, powdery mildew, damping-off, root rot, stalk break, and brown blotch, which are caused by four higher and lower pathogenic fungi. At present, it is widely applied as an ideal bactericide for achieving pollution-free vegetables and fruits. At present, azoxystrobin related dosage forms that have been developed include an aqueous suspension, water dispersible granules, a microemulsion, a missible oil, and the like.

[04] At present, technologies of preparing effective components of a pesticide into aqueous nanosuspensions have been found, however, there are still some defects in these technologies as follows: (1) during a preparation process of most of the aqueous nanosuspensions, an organic solvent is inevitably used,, which is not be friendly to an environmental protection and will lead to an environmental pollution; (2) at present, the pesticide is adsorbed by a nano material carrier in most cases, but the organic solvent is used during a loading, which results in a low drug-loading capacity and an adsorption rate of the carrier to the pesticide; and (3) Some aqueous nanosuspensions can not go to industrial production and application because of high energy consumption and costs, difficult preparation

SUMMARY

[05] The present disclosure provides an azoxystrobin aqueous nanosuspension and a preparation method thereof.

[06] In the present disclosure, the following technical solutions are as follow: 1

[07] The present disclosure relates to an Azoxystrobin aqueous nanosuspension, which includes components in percentage by mass: 10%-20% of Azoxystrobin, 10%-30% of LU501696 hydrophobic dispersible nanosilicon dioxide, 2%-10% of wetting dispersant, 0.2%-3% of thickener, 1%-5% of antifreezing agent, 0.01%-0.2% of preservative, and the balance of water.

[08] A grain diameter of the hydrophobic dispersible nanosilicon dioxide ranges from 10 to nm, and a mass ratio of the azoxystrobin to the hydrophobic dispersible nanosilicon dioxide is 1: 0.5-1.5.

[09] The wetting dispersant is one or more of calcium lignosulphonate, fatty alcohol- polyoxyethylene ether, dodecylbenzene sulfonic acid, phenylethyl phenol polyoxyethylene polyoxypropylene ether, methylene binaphthalene sulfonate, alkylphenol formaldehyde condensate sulfonate, and nonylphenol polyoxyethylene phosphate.

[10] The thickener is one or more of xanthan gum, aluminum-magnesium silicate, carboxymethylcellulose, sodium acrylate, polyvinyl alcohol, and polyvinylpyrrolidone.

[11] The preservative is one or more of aqueous solution of formaldehyde, citric acid, benzoic acid, sorbic acid, potassium sorbate, sodium o-phenylphenate, sodium propionate, hexamethylenetetramine, and sulphurous acid.

[12] The antifreezing agent is one or more of ethylene glycol, propylene glycol, glycerol, glycerol ether diethylene glycol, methyl propylidene diethylene glycol, urea, sodium nitrite, carbonate, calcium chloride, and calcium nitrite.

[13] A preparation method of the azoxystrobin aqueous nanosuspension is characterized by including the following steps: taking raw materials in a ratio, dissolving the azoxystrobin in an organic solvent, adding a hydrophobic dispersible nanosilicon dioxide carrier, and obtaining an oil phase; adding the wetting dispersant, the antifreezing agent, and the preservative into the water, dissolving with stirring, and obtaining a water phase; dropping the water phase into the oil phase while stirring; after dropping the water phase, distilling under a reduced pressure with stirring in a water bath of 30°C, and distilling the organic solvent completely; and finally, adding the thickener and the balance of water, shearing, emulsifying uniformly, and obtaining the azoxystrobin aqueous nanosuspension.

[14] The organic solvent is methanol or/and acetone, and a use level of the organic solvent is a use level of making the azoxystrobin dissolved completely.

[15] The prevent disclosure has two main characteristics: on one hand, the industrial and low-cost hydrophobic dispersible nanosilicon dioxide is used as the carrier, which can be dispersed uniformly in the oil phase, and adsorb a drug with the azoxystrobin to the utmost extent under a hydrophobic interaction, and in addition, the carrier achieves a synergistic effect due to its a bacteriostatic activity; on the other hand, in a technology of controlling a drug- loading capacity, an adsorption rate, and a grain diameter by a dissolvability, after a fixed quantity of azoxystrobin technical material (the dissolvability in water is 6 mg/L at 20°C) is dissolved in a specific organic solvent, and the hydrophobic dispersible nanosilicon dioxide is added, an adsorption happens between the carrier and the drug under the hydrophobic interaction, but the adsorption rate and the drug-loading capacity are low under an influence of an adsorption equilibrium; an addition of a poor solvent (the water) can reduce the dissolvability of the azoxystrobin in a mixed solvent until the solvent is supersaturated, making azoxystrobin molecules crystallized out unceasingly; drug-loading nano-particles to which the azoxystrobin 2 has been adsorbed will be used as crystal nuclei, and the azoxystrobin molecules will be crystallized out preferentially on these crystal nuclei, which forms a growing process of a LU501696 crystal; the dissolvability is reduced continuously in the growing process; in case that a sufficient amount of water is added, the dissolvability of the azoxystrobin technical material in a solution will be very low, a distillation will be conducted under a reduced pressure in a later period of a process, the organic solvent will be decreased constantly until it is distilled completely, which means that almost all of the azoxystrobin can be adsorbed or deposited onto the nanosilicon dioxide, with the adsorption rate almost up to 100%; during an implementation, an addition of an appropriate surfactant can avoid an agglomeration of the particles in this process, so that finally, the drug-loading capacity can be calculated based on a feed ratio w = _— Fer drug an —, without recycling the technical material; and an objective of Fed drug quantity + carrier quantity controlling the grain diameter can also be fulfilled by making an adjustment in the feed ratio and the drug-loading capacity. A key point of the present disclosure is to control a ratio of the azoxystrobin to the hydrophobic dispersible nanosilicon dioxide, that is, an effective component of an added pesticide is adsorbed by the silicon dioxide completely by adding the poor solvent or distilling the organic solvent, which can be quantified in a large production.

[16] After the azoxystrobin aqueous nanosuspension is determined by a laser particle size distribution instrument, an average grain diameter ranges from 50 to 200 nm, a particle size is controllable, and a distribution range is narrow. The drug product is free of the organic solvent, environmentally friendly, small in the grain diameter, high in liquidity, and strengthened in permeability and conductivity in leaves; a specific surface area is increased, making a dissolution rate of the technical material elevated; as surface energy is increased, the drug product is easier to adsorb to plants; and with strengthening in wind and rainwash resistance, pesticide residues flowing in soil may be reduced. The drug product can fulfill objectives of improving an effect and prolonging a lasting validity period under a controlled-release effect.

DETAILED DESCRIPTION OF THE EMBODIMENTS Embodiment 1

[17] 12 g of azoxystrobin technical material is weighed, and is added into 600 mL of methanol for dissolving with stirring, then, a mixed solution is added into 12 g of hydrophobic dispersible nanosilicon dioxide, and an oil phase is obtained; 2 g of calcium lignosulphonate, 4 g of fatty alcohol-polyoxyethylene ether, 5 g of ethylene glycol, and 0.05 g of sodium o- phenylphenate are added into 60 g of water for dissolving while being stirred, and a water phase is obtained; the water phase is dropped into the oil phase slowly while being stirred quickly; after the water phase is dropped completely, a reduced pressure distillation is conducted in a water bath of 30°C with stirring, and the methanol is distilled completely; and finally, 0.2 g of xanthan gum, 1 g of aluminum-magnesium silicate, and the balance of 100 g of water are added for uniform shearing and emulsifying, and the 12% azoxystrobin aqueous nanosuspension is obtained. After detection, an average grain diameter of the product is 100 nm. Embodiment 2

[18] 20 gofazoxystrobin technical material is weighed, and is added into 300 mL of acetone for dissolving with stirring, then, a mixed solution is added into 10 g of hydrophobic dispersible nanosilicon dioxide, and an oil phase is obtained; 2 g of calcium lignosulphonate,0.8 g of alkylphenol formaldehyde condensate sulfonate, 4.8 g of nonylphenol polyoxyethylene phosphate, 5 g of ethylene glycol, and 0.05 g of benzoic acid are added into 50 g of water for dissolving while being stirred, and a water phase is obtained; the water phase is dropped into 3 the oil phase slowly while being stirred quickly; after the water phase is dropped completely, a reduced pressure distillation is conducted in a water bath of 30°C with stirring, and the acetone LU501696 is distilled completely; and finally, 0.2 g of xanthan gum, 1 g of aluminum-magnesium silicate, and the balance of 100 g of water are added for uniform shearing and emulsifying, and the 20% azoxystrobin aqueous nanosuspension is obtained. After detection, an average grain diameter of the product is 165 nm. Embodiment 3

[19] 20 gofazoxystrobin technical material is weighed, and is added into 300 mL of acetone for dissolving with stirring, then, a mixed solution is added into 30 g of hydrophobic dispersible nanosilicon dioxide, and an oil phase is obtained; 2 g of dodecylbenzene sulfonic acid, 3 g of phenylethyl phenol polyoxyethylene polyoxypropylene ether, 1 g of methylene binaphthalene sulfonate, 5 g of ethylene glycol, and 0.05 g of benzoic acid are added into 35 g of water for dissolving while being stirred, and a water phase is obtained; the water phase is dropped into the oil phase slowly while being stirred quickly; after the water phase is dropped completely, a reduced pressure distillation is conducted in a water bath of 30°C with stirring, and the acetone is distilled completely; and finally, 0.2 g of xanthan gum, 1 g of aluminum-magnesium silicate, and the balance of 100 g of water are added for uniform shearing and emulsifying, and the 20% azoxystrobin aqueous nanosuspension is obtained. After detection, an average grain diameter of the product is 75 nm.

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[21] The 12% azoxystrobin aqueous nanosuspension obtained in the embodiment 1 was subjected to an indoor biological activity assay. A specific experiment method was as follows: a toxicity of a 25% azoxystrobin suspension agent and the 12% azoxystrobin aqueous nanosuspension to pseudoperonospora cubensis was determined in a pot culture method. On the basis of a preliminary test, agents for tests were prepared into mother solutions with the same concentration, and then, were diluted into solutions under the tests, with 7 concentration gradients; and clear water was set as a solvent control. When a cucumber seedling grew to 6 true leaves, a pesticide was sprayed, that is, the pesticide was sprayed uniformly on front and back sides of the leaves; a pseudoperonospora cubensis spore suspension was sprayed within 24 h after the pesticide was sprayed, and the cucumber seedling was cultured for 96 h in a greenhouse (T=20°C to 25°C, RH=90% to 95%); and results were investigated, ECso was calculated, and a toxic regression equation of the agents was obtained with a least square method. Experimental results were shown in Table 2. Table 2 showed that a biological activity 4 of the azoxystrobin aqueous nanosuspension was significantly higher than that of the ordinary azoxystrobin suspension agent. LU501696 Table 2 Test results of indoor biological activity assay Agent Toxic regression equation ECso Correlation coefficient Cam) 25% azoxystrobin suspension y=0.2331x+4.5333 100.77 0.9835 agent 12% azoxystrobin aqueous y=0.6818x+4.1682 16.60 0.9781 nanosuspension

[22] The embodiment 1 was subjected to a pesticide effect of a farmland; and the agents for the tests were the 25% azoxystrobin aqueous nanosuspension and the 12% azoxystrobin aqueous nanosuspension, which were used for preventing and controlling cucumber downy mildew, and conducting a contrast test of the pesticide effects. There were 5 treatments, 4 repeats, and a total of 20 plots, each of which has a spraying area of 20 m°; and all plots were arranged in a randomized block method. A conventional spraying is implemented. 10 cucumber plants were selected in each test plot in a five-point sampling method, disease indexes of cucumbers prior to a pesticide application, after 7 d of the pesticide application for the first time, and after 7 d and 14 d of the pesticide application for the second time were investigated, and a prevention and control effect was calculated. Experimental results were shown in Table 3. Statistical results showed that the azoxystrobin aqueous nanosuspension had the prevention and control effect on the cucumber downy mildew; and compared with the ordinary azoxystrobin suspension agent, at least a half of dosage was saved under the same prevention and control effect. Table 3 Results of pesticide effect test of farmland Treatment Dosage Prevention and control effect After 7 days of After 7 days of After 14 days of pesticide pesticide pesticide application for the | application for the | application for the first time second time second time 12% azoxystrobin 20 mL/mu 60.4 70.4 78.5 aqueous nanosuspension 12% azoxystrobin 30 mL/mu 67.2 81.2 86.3 aqueous nanosuspension 12% azoxystrobin 40 mL/mu 79.1 88.9 94.6 aqueous nanosuspension 25% azoxystrobin 40 mL/mu 68.3 79.0 84.1 suspension agent

Claims

WHAT IS CLAIMED IS: LUS01696

1. An azoxystrobin aqueous nanosuspension, comprising components in percentage by mass: 10%-20% of azoxystrobin, 10%-30% of hydrophobic dispersible nanosilicon dioxide, 2%-10% of wetting dispersant, 0.2%-3% of thickener, 1%-5% of antifreezing agent, 0.01%-

0.2% of preservative, and the balance of water, wherein a grain diameter of the hydrophobic dispersible nanosilicon dioxide ranges from 10 to 30 nm, and a mass ratio of the azoxystrobin to the hydrophobic dispersible nanosilicon dioxide is 1: 0.5-1.5.

2. The azoxystrobin aqueous nanosuspension according to claim 1, characterized in that, the wetting dispersant is one or more of calcium lignosulphonate, fatty alcohol-polyoxyethylene ether, dodecylbenzene sulfonic acid, phenylethyl phenol polyoxyethylene polyoxypropylene ether, methylene binaphthalene sulfonate, alkylphenol formaldehyde condensate sulfonate, and nonylphenol polyoxyethylene phosphate.

3. The azoxystrobin aqueous nanosuspension according to claim 1, characterized in that, the thickener is one or more of xanthan gum, aluminum-magnesium silicate, carboxymethylcellulose, sodium acrylate, polyvinyl alcohol, and polyvinylpyrrolidone.

4. The azoxystrobin aqueous nanosuspension according to claim 1, characterized in that, the preservative is one or more of aqueous solution of formaldehyde, citric acid, benzoic acid, sorbic acid, potassium sorbate, sodium o-phenylphenate, sodium propionate, hexamethylenetetramine, and sulphurous acid.

5. A preparation method of the azoxystrobin aqueous nanosuspension according to claim 1, characterized in that, it comprises the following steps: taking raw materials in a ratio, dissolving the azoxystrobin in an organic solvent, adding a hydrophobic dispersible nanosilicon dioxide carrier, and obtaining an oil phase; adding the wetting dispersant, the antifreezing agent, and the preservative into the water, dissolving with stirring, and obtaining a water phase; dropping the water phase into the oil phase while stirring; after dropping the water phase, distilling under a reduced pressure with stirring in a water bath of 30°C, and distilling the organic solvent completely; and finally, adding the thickener and the balance of water, shearing, emulsifying uniformly, and obtaining the azoxystrobin aqueous nanosuspension.

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