Prochloraz manganese nano-suspension dispersion

Abstract

A prochloraz manganese nano-suspension, the particle size of the prochloraz manganese nano-suspension being less than 100 nanometers, especially less than 50 nanometers. The prochloraz manganese nano-suspension is formed by diluting and mixing three components with water: component A: a prochloraz solution prepared by dissolving prochloraz in at least one ketone solvent; component B: a manganese chloride solid or a manganese chloride aqueous solution; and component C: a mixture consisting of at least one water-soluble polymer adjuvant.

Description

Prochloraz manganese salt nanosuspension dispersion

Technical field

[0001] The present invention belongs to the field of nano pesticides, and particularly relates to the preparation of suspension dispersions of water- and solvent-insoluble pesticides with particle sizes less than 100 nanometers, especially less than 50 nanometers. [Background Technology]

[0002] Modern agricultural production requires the use of pesticides. Improving the formulation performance of existing pesticides, increasing their efficacy, reducing their dosage, and mitigating their impact on the environment are of great significance to the sustainable development of agriculture.

[0003] An effective way to achieve pesticide reduction is to effectively reduce the particle size of the active ingredients in pesticide formulations. For water-insoluble pesticides, the minimum size is a few nanometers. Nanopesticides refer to formulations in which the pesticide particles are at the nanometer scale (1 to 100 nm). The particle size of traditional pesticide formulations is on the micrometer scale, ranging from a few microns to tens of microns or even larger. If the particle size is reduced to nanometers, the size is reduced by a thousand times. Theoretically, the number of particles can increase by a billion times, and the surface area can increase by a thousand times. The dramatic increase in the number and surface area of ​​pesticide particles allows for more even dispersion on the leaves, more extensive contact with the target, and full and enhanced efficacy.

[0004] On April 1, 2019, the International Union of Pure and Applied Chemistry (IUPAC), celebrating its 100th anniversary, announced its "Top 10 Chemical Inventions That Will Change the World," with nanopesticides topping the list. This is due to the growing global population, projected to approach 10 billion by 2050. Feeding this large population requires a significant increase in agricultural output while minimizing the environmental impact of land use, including reducing pesticide pollution and water consumption. Nanopesticides, with their small particle size and improved target absorption, offer a promising tool for addressing the key challenges of traditional pesticides: environmental pollution, pesticide accumulation in organisms, and the significant increase in pest and disease resistance. While nanopesticides are by no means the only path to sustainable agricultural development, they certainly offer a lower impact on the environment and human health, contributing to a more sustainable future for the planet.

[0005] Prochloraz, chemically known as N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide, is a white crystal with a melting point of 46.5-49.3°C. It is non-volatile, non-corrosive, and non-explosive, with a vapor pressure of 0.48 mPa (20°C). Its solubility in water at 25°C is 34.4 mg / L. It is soluble in most organic solvents and relatively stable under normal storage conditions, but unstable under alkaline and acidic conditions. Prochloraz, originally developed and produced by the German company Agfr, is a highly effective, broad-spectrum, low-toxic imidazole fungicide. It has both protective and eradicative properties, as well as systemic and conductive properties. It primarily inhibits sterol biosynthesis and is particularly effective against various plant diseases caused by ascomycetes. It also controls rice blast, seedling blight, mushroom brown spot, rapeseed sclerotinia rot, and anthracnose on various crops.

[0006] Prochloraz manganese salt is a complex of prochloraz and manganese chloride, with prochloraz and manganese ions as its active ingredients. Compared to prochloraz, prochloraz manganese salt is safer because the manganese ions in it inhibit spore germination and mycelial growth of pathogens. This makes prochloraz manganese salt more effective and safer, and it can more effectively protect crops from pathogens.

[0007] Prochloraz manganese salt, chemical name is N-propyl-N-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide-manganese chloride, chemical formula is [C 15 H 16 Cl3N3O2]4·MnCl2, with a molecular weight of 1635.51 and a CAS number of 278-301-3. The molecular structure is shown in Formula (1). The original drug is a white to brown, granular powder with a slightly aromatic odor. Its melting point is 141-142.5°C, its solubility in water is 40 mg / L, its solubility in acetone is 7 g / L, and its vapor pressure is 0.02 Pa (20°C). This complex rapidly separates in aqueous solutions or suspensions, achieving a resolution of 55% within 4 hours at 25°C.

[0008] Since the 1990s, my country has been conducting extensive field trials on prochloraz manganese salt, demonstrating its significant efficacy against rapeseed sclerotinia rot, rice panicle, stripe leaf blight and seedling blight, banana leaf spot, peanut brown spot, watermelon vine blight, citrus storage and preservation, tulip bulb rot, grape gray mold and black bean disease, and tobacco brown spot, all at relatively low dosages. In 2008, a 1000-2000 times dilution was found to be significantly effective against mango anthracnose. In 2012, trials were conducted on citrus black spot, and EC 50It was subsequently found that an 800-1000 times dilution could achieve a 47.9%-63.4% control effect on garlic leaf blight, was safe for crops, and had a certain yield-increasing and yield-guaranteed effect on garlic bulbs.

[0009] The addition of manganese salts alters the original physical properties of prochloraz, rendering it insoluble in both water and organic solvents, forcing its formulation to be processed as a wettable powder. Currently, pesticide formulations processed through mechanical pulverization produce particle sizes ranging from a few microns to tens of microns or even larger. These large pesticide particle sizes hinder efficacy, leading to increased dosage and increased resistance in target insecticides. Improving the formulation and enhancing the efficacy of pesticides containing polyvalent metal ions is a global challenge.

[0010] The existing process for synthesizing the technical of prochloraz manganese salt and processing the wettable powder formulation is as follows: (1) Technical synthesis. Prochloraz manganese salt is dissolved in toluene, and manganese chloride is added to carry out a complexation reaction to obtain a block precipitate of prochloraz manganese salt. After separation, washing, and drying, the technical of prochloraz manganese salt is obtained. (2) Preparation processing. The solid technical of prochloraz manganese salt is used as the raw material, and the prochloraz manganese salt preparation is obtained by crushing, grinding, mixing, etc. This preparation process requires corresponding workshops and production equipment, such as filters, dryers, crushers, grinders, and mixers. The process is both lengthy and energy-consuming.

[0011] [Summary of the invention]

[0012] One of the purposes of the present invention is to overcome the shortcomings of the prior art and provide a new idea and method for preparing a wettable powder formulation of prochloraz manganese salt, which is different from the prior art. Through the dilution process with water, prochloraz and manganese chloride react to generate prochloraz manganese salt, thereby providing an apparently water-soluble and transparent nano-suspension dispersion of prochloraz manganese salt, which can be directly used for spraying.

[0013] The nano-suspension of prochloraz manganese salt described in the present invention can be loaded into pesticide spraying equipment for spraying. It mainly prevents and controls the following diseases: early and late blight, powdery mildew, damping-off, gray mold, mosaic disease, brown spot, and scab in tomatoes; leaf spot, anthracnose, blue mold, and scab in citrus; leaf spot, brown spot, powdery mildew, and rust in apples; scab, powdery mildew, rust, stem blight, and yellow leaf disease in pears; downy mildew, vine blight, gray mold, and mosaic disease in cucumbers; blast, sheath blight, seedling blight, damping-off, and false smut in rice; and anthracnose, blossom blight, soft rot, gray mold, and angular leaf spot in cotton. The product is effective and has stable and reliable quality.

[0014] The innovative ideas of the present invention are as follows:

[0015] The precursor of prochloraz manganese salt is prochloraz. Prochloraz is insoluble in water but soluble in organic solvents with great solubility. Prochloraz dissolves in organic solvents as a single molecular dispersion, serving as one component. The manganese chloride that reacts with it, on the other hand, is ionically dispersed in water, consisting of manganese ions and chloride ions, serving as another component. When the two interact under stirring, the manganese ions and prochloraz molecules readily react to form prochloraz manganese salt. By controlling the reaction conditions, the nucleation and crystallization growth of the resulting prochloraz manganese salt can be controlled, resulting in a nano-suspension dispersion of prochloraz manganese salt.

[0016] Under conditions where the stirring speed can be controlled, an organic solvent solution of one component (e.g., prochloraz) is added to an aqueous solution of another component (e.g., manganese chloride). The addition and mixing can also be performed in the opposite order. By controlling the dropwise addition rate and stirring speed, nanoparticles of prochloraz manganese salt and a suspension thereof can be generated.

[0017] The generated nanocrystals of prochloraz manganese salt can be temporarily and stably dispersed in an aqueous system when the particle size is very small and the number is small. As the nanocrystals continue to form, they collide, grow, and aggregate with each other. When the size of the nanocrystals of prochloraz manganese salt approaches the wavelength of visible light, the system begins to exhibit opalescence. When it exceeds this wavelength, it gradually becomes opaque. Combined with the effect of gravity, the system will precipitate as crystals. To prevent this phenomenon, a water-soluble polymer additive must be added to the system. After dissolving in water, the water-soluble polymer additive exists in the form of a random coil structure. A random coil is a loose spherical structure formed by the spontaneous curling of water-soluble polymer chains. The interior is composed of the lipophilic and hydrophobic molecular backbone, while the exterior is composed of hydrophilic polar groups. Numerous random coils aggregate into micelles. At this point, when the nanocrystals of prochloraz manganese salt generated in the system are less than 100nm, especially less than 50nm, they diffuse into the interior of random coils and micelles under the shear force of mechanical stirring, isolating and preventing the effective collision, growth, precipitation, and settling of the crystals. Therefore, the water-soluble polymer additive disperses, suspends, stabilizes, and protects the nanocrystals of prochloraz manganese salt. When the crystal size is below 100nm, especially below 50nm, the system appears clear and transparent, and appears water-soluble, exhibiting the "Tyndall phenomenon."

[0018] It's important to note that during the production of prochloraz manganese salt nanoparticles, the rate of component addition and the stirring speed of the system, which influence the amount of reactants added per unit time and the uniformity of dispersion of the product, are crucial factors influencing the size of the resulting nanoparticles. Regarding the addition rate, the goal is to produce nanoparticles less than 100 nanometers in size, with the clarity and transparency of the system serving as the criterion. This is based on the theory that when the particle size is less than one-quarter of the lower limit of the visible light wavelength (400-760 nanometers), there is no significant refraction or reflection, and therefore the system is transparent. Conversely, if the system exhibits opalescence or opacity, it indicates that the particle size is greater than 100 nanometers.

[0019] To achieve this goal, the following points must be focused on:

[0020] ① The mixing speed of the two-component solution (i.e., the speed at which one component is added) should not be too fast. If added too quickly, the two components will be unevenly dispersed, leading to localized excessive concentrations. This will also accelerate the formation of product crystals, resulting in a large number of crystals. This may lead to aggregation between nanocrystals, resulting in larger grain sizes. If the system exhibits opalescence, this indicates that the grain size is already several hundred nanometers. Therefore, the speed at which one component is added should be such that the system remains transparent.

[0021] ② The stirring speed of the system should be appropriately increased. The stirring speed of the system is related to the formation and dispersion rate of the product nanoparticles in the aqueous phase. Adequate stirring and rapid diffusion promote the rapid formation and dispersion of nanoparticles, maintain small particle size, and avoid aggregation of particles. The stirring speed should be coordinated with the addition rate of the components and should also be based on maintaining the transparency of the system.

[0022] Explanation of terms

[0023] Dispersed system: A dispersed system is formed when one or more substances are dispersed in another. The dispersed substance in a dispersed system is called the dispersed phase, and the other substance is called the dispersion medium. Based on the size of the dispersed phase particles, dispersed systems are categorized as: molecular (ionic) dispersed systems (particle size < 1 nm) and colloidal dispersed systems (particle size < 100 nm).

[0024] Colloids and Sols: A colloid is a state in which matter exists at a certain degree of dispersion, rather than being an inherent state of a particular type of substance. Many normally insoluble substances can, under appropriate conditions, disperse in a medium to form a seemingly uniform solution. While superficially indistinguishable from a true solution, their diffusion rate and permeability, among other factors, place them within the realm of colloidal substances and are referred to as sols.

[0025] Classification of Colloidal Solutions: Based on their stability and the structure of their colloidal particles, they are divided into the following categories: 1. Lyophobic sols, formed by insoluble substances dispersed in a dispersion medium, are referred to as sols. These particles consist of varying numbers of molecules, exhibiting large interphases and apparent free energies. These sols are highly unstable and easily disrupted, leading to aggregation and irreversible return to their original state. 2. Solutions of polymer compounds, whose molecular size reaches the colloid range and exhibits colloidal properties, are true molecular solutions, thermodynamically stable, and reversible systems. These sols are also known as lyophilic sols.

[0026] Tyndall effect: When a beam of light passes through a colloid, a bright "pathway" can be observed in the colloid perpendicular to the incident light. This phenomenon, also known as the Tyndall effect, is essentially the scattering of light when propagating through a colloid. This phenomenon occurs primarily because the particle size of colloidal particles ranges from 1 to 100 nm, resulting in a significant scattering effect of visible light passing through the colloid, while true solutions scatter very little light. Colloids exhibit a pronounced Tyndall effect, while true solutions with dispersed molecules exhibit virtually no light scattering. Therefore, it is often used to distinguish colloidal solutions from true solutions.

[0027] If the particles are smaller than the wavelength of the incident light, light scattering occurs, with the light waves radiating outward around the particles, a phenomenon known as scattered light or opalescence. The Tyndall effect is essentially a phenomenon of light scattering, also known as opalescence. True solutions scatter light very weakly. The intensity of scattered light also increases with increasing particle concentration in the dispersed system. Therefore, when the observed solution is clear and transparent, it indicates that the particle size in the solution is less than 100 nm, and the Tyndall effect may occur. If the particles approach or exceed the wavelength of the incident light (400-740 nm), significant light reflection occurs. When the solution displays increasing opalescence, turbidity, or even opacity, the particle size has increased to near micrometers or above.

[0028] System: The term "system" refers to the suspension dispersion formed by mixing two components under controlled addition rate and stirring during the preparation of the prochloraz manganese salt nanosuspension of the present invention. The system is the target product—a nanosuspension dispersion—formed by mixing water, a precursor solution, a water-soluble polymer additive, and the resulting prochloraz manganese salt.

[0029] Component: A component is a composition comprising one or more ingredients. In principle, any ingredient used in this invention can constitute a component on its own. However, for ease of packaging, transportation, and use, the components should be simplified. The principles are: 1) the ingredients should not react with each other; 2) the number of components should not be too large.

[0030] Ingredients: The so-called ingredients refer to the raw materials used in the present invention, including prochloraz, organic solvent, manganese chloride, water-soluble polymer additives and water.

[0031] Precursor: The so-called precursor refers to the parent substance used to generate the target product prochloraz manganese salt, namely prochloraz.

[0032] Water-soluble polymer additives are macromolecular substances containing hydrophilic polar groups that are soluble in water. They are also called polymer surfactants or active agents. Water-soluble polymer additives can provide dispersion, suspension, emulsification, and stabilization. Based on the nature of the groups, they can be categorized as anionic, cationic, zwitterionic, and nonionic polymer additives.

[0033] Particle size: also known as particle size; refers to the size of the crystals of prochloraz manganese salt formed by the interaction of the precursor in the system with the manganese salt under the dispersion of water-soluble polymer additives. It also includes the particle size formed by other pesticide varieties compounded with it, and does not specifically refer to the microscopic morphological structure of the crystals.

[0034] Sub-100 nanometers is a statistical classification of pesticide particle sizes within a system. All pesticide particle sizes within a suspension exhibit a statistical distribution. The sub-100 nanometer nanosuspension described herein means that at least 80% of the pesticide particles are smaller than 100 nanometers. Thus, particles larger than 100 nanometers constitute only a small fraction.

[0035] Effective stirring speed: The so-called effective stirring speed refers to the ability, under a certain addition method, to disperse the nanocrystals generated in the system promptly when one component is added to another, by stirring at a speed no less than the effective stirring speed, preventing grain growth and aggregation, and preventing the grain size from increasing to several hundred nanometers. Transparency of the resulting solution is a sign of effective stirring.

[0036] Effective stirring: The addition of components and the stirring method and speed have a significant impact on the resulting liquid. Stirring methods include mechanical stirring, multi-point mechanical stirring, manual stirring, and multi-point manual stirring. Fast stirring speeds are associated with optimal results. If the resulting liquid is transparent, the stirring is considered effective. Otherwise, the stirring is considered ineffective.

[0037] Addition method: The so-called addition method includes the order in which the different components are mixed with water to form two components. The two components can be added one after the other, or vice versa. Addition methods include continuous addition, intermittent addition, trickle addition, dropwise addition, spray addition, and addition at a fixed or mobile position. The addition method is preferably to achieve rapid mixing and dispersion.

[0038] Addition speed: After determining the addition method, control the amount of components added with the goal of achieving effective stirring.

[0039] The nano-suspension of prochloraz manganese salt of the present invention refers to a nano-suspension of prochloraz manganese salt with a size of less than 100 nanometers; the nano-suspension of prochloraz manganese salt with a size of less than 100 nanometers is formed by diluting and mixing three components with water:

[0040] Component A: a solution of prochloraz dissolved in one or more ketone solvents.

[0041] Component B: Manganese chloride solid or combined with water to form a transparent aqueous solution.

[0042] Component C: A mixture of one or more water-soluble polymer additives, or a transparent solution formed by adding an appropriate amount of water to reduce the viscosity.

[0043] The ketone solvent can be acetone which is soluble in water, or a mixture of acetone and cyclohexanone which is insoluble in water.

[0044] The water-soluble polymer auxiliary agent is a nonionic surfactant.

[0045] The nonionic surfactant may be selected from water-soluble starch, cellulose and its derivatives, water-soluble guar gum and its derivatives, polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, alkylphenol polyoxyethylene ether, arylphenol polyoxyethylene ether, castor oil polyoxyethylene ether, alkyl polyglycoside, Tween, polyvinyl alcohol, etc. Preferably, polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, alkylphenol polyoxyethylene ether, arylphenol polyoxyethylene ether, castor oil polyoxyethylene ether, alkyl polyglycoside, Tween, etc.

[0046] Furthermore, the nano-suspension of prochloraz manganese salt with a size below 100 nanometers has a stability period of hours.

[0047] Stable period

[0048] The prochloraz manganese salt nano suspension of the present invention's preparation is a class transparent appearance, apparent water-soluble solution, but itself is not a thermodynamically stable solution. Therefore, the time that nano suspension keeps the transparent state of appearance is not infinitely long, but has a plateau. Consider from the characteristics of spraying operation, after the nano suspension is prepared, the operating time needed should be at least more than 1 hour, can like this describe the length of the plateau time in hours. Thus, the present invention proposes that there is the concept of "plateau" in the following nano suspension of 100nm. That is, the following level nano suspension of 100nm prepared by the present invention finishes the spraying operation during solution keeps transparency, and the plateau should reach 1 hour at least.

[0049] From the application perspective, the stable period can be further divided into four time periods: less than 1 hour, 1 to 2 hours, 2 to 5 hours, and more than 5 hours.

[0050] During the stabilization period, the nanoscale suspension remains transparent, which ensures that the particle size remains less than 100 nm.

[0051] Hourly stability period is analyzed from the perspective of spraying operation:

[0052] The stabilization time is about 1 hour, which is not sufficient for spraying operations. It is difficult to achieve a stable period of more than 5 hours for multi-component nanosuspensions. The stabilization time is between 2 and 5 hours, which is sufficient for most pesticide spraying equipment.

[0053] The hour-level stabilization period mentioned in the present invention refers to a stabilization time between 1 and 5 hours.

[0054] For the hourly stable period, further detailed division can be carried out.

[0055] The basic period for spraying operation is 1 to 2 hours; in most cases, the spraying equipment can complete the operation.

[0056] 2 to 5 hours is a sufficient period for spraying operations; it can be used to accommodate spraying operations that are delayed due to special circumstances.

[0057] Composition and additives of prochloraz manganese salt nanosuspension

[0058] Traditional prochloraz manganese salt pesticide formulations, such as wettable powders, are typically single-component and can be sprayed after dilution with water. However, the pesticide particles are typically larger than microns in size. The present invention, in order to obtain a suspension dispersion with nanometer-sized particles, employs a three-component formulation and, following a specific method, dilutes the suspension dispersion with water to produce a nanoscale suspension dispersion of prochloraz manganese salt with a particle size of less than 100 nanometers.

[0059] Three-component solution

[0060] The suspension of prochloraz manganese salt below 100 nanometers has a stable period of hours and is a system generated by the reaction of three components. They are:

[0061] Component A: Prochloraz solution dissolved in acetone or acetone / cyclohexanone mixed solvent.

[0062] Component B: Manganese chloride solid or in combination with water.

[0063] Component C: A mixture of one or more water-soluble polymer additives, or a transparent solution formed by adding an appropriate amount of water to reduce the viscosity.

[0064] Component ratio for generating nano-suspension dispersion of prochloraz manganese salt

[0065] In component A and component B, the amount of precursors used is the basis for determining the composition of the two components. Prochloraz in component A is the precursor for the formation of nano-prochloraz manganese salt and is the basis for determining the composition of component B.

[0066] The present invention takes the case where 20 grams of prochloraz manganese salt needs to be sprayed on 1 / 15 hectare of field as an example, and a three-component design is performed based on the generation of a 20-gram suspension of prochloraz manganese salt with a particle size below 100 nm.

[0067] Component A requires about 20 grams of prochloraz as a precursor, and dissolution requires about 40 grams or more of acetone or a mixed solvent of acetone / cyclohexanone.

[0068] Component B, determine the amount of manganese chloride required to react with prochloraz. It is generally believed that manganese ions and prochloraz form a 1:4 molecular complex structure, based on which the amount of manganese chloride can be calculated.

[0069] Component C, determine the type and amount of water-soluble polymer additives, based on the appearance of a transparent state, which is affected by the amount of water used for dilution.

[0070] The ratio of the amount of the auxiliary agent to the amount of water used for dilution is at least within 1:1200, preferably within 1:1000, and more preferably within 1:800.

[0071] Prochloraz: manganese chloride mass ratio

[0072] There is no strict ratio between prochloraz and manganese ions. To ensure a complete reaction in industrial production, the ratio of the two is large, which is the upper limit. The present invention adopts a ratio lower than this for the following reasons: ① The large amount of manganese ions and high concentration are not conducive to the formation and stability of small-sized grains; ② Using a low amount of manganese salt means that even if the reaction is not complete, all its components are independently usable fungicides; ③ The preparation process of the nanosuspension does not require industrial production of water washing, separation and drying of prochloraz manganese salt, and no components are lost. The molecular ratio and mass ratio between the two are as follows:

[0073] Prochloraz: manganese chloride = 1:0.3 (molecular ratio); 100:10 (mass ratio) (theoretical upper limit)

[0074] Preferably, prochloraz: manganese chloride = 1:0.275 (molecular ratio); 100:9 (mass ratio) (industrial production ratio)

[0075] More preferably, prochloraz: manganese chloride = 1:0.25 (molecular ratio); 100:8 (mass ratio) (practical application)

[0076] Water-soluble polymer additives

[0077] (1) The prochloraz manganese salt is diluted with water and then barrel-mixed to obtain a ready-to-use nano-suspension dispersion of the prochloraz manganese salt. A water-soluble polymeric additive with dispersing and suspending properties is added to this solution, resulting in the prochloraz manganese salt being dispersed and suspended in the polymeric additive solution at nanometer sizes. Because the particle size is less than 100 nanometers, the resulting nano-suspension dispersion of the prochloraz manganese salt appears transparent and water-soluble.

[0078] (2) Water-soluble polymer additives are polymer surfactants that disperse, suspend, stabilize, and increase viscosity of nanoparticles. This is due to their hydrophobic chain structure and hydrophilic groups. These groups, found on the side and end of the macromolecular chain, include hydroxyl, carboxyl, carboxymethyl, sulfonic acid, sulfate, phosphate, amino, and quaternary ammonium salts. Based on their source, they are classified as natural or synthetic polymers. Based on the nature of their hydrophilic groups, they are classified as anionic, cationic, nonionic, and zwitterionic polymers.

[0079] (3) The principles for selecting water-soluble polymer adjuvants in the present invention are: 1. They must stabilize, disperse, and suspend the pesticide nanoparticles generated in the system; 2. They must be unaffected by the reaction between polyvalent metal ions and prochloraz; and 3. They must be as environmentally friendly as possible. Therefore, the present invention selects non-ionic polymer adjuvants from natural substances and their derivatives, such as various polyoxyethylene ethers with hydrophobic groups such as fatty alcohols, fatty acids, fatty amines, alkylphenols, arylphenols, and oleyl groups, such as the Peregal series, OP series, Tween series, polyol series, ricinoleic acid series, and alkyl polyglycosides. However, nonylphenol polyoxyethylene ethers, which are known to have estrogenic toxicity, should be avoided.

[0080] (4) The nano-suspension dispersion of prochloraz manganese salt is directly generated by the reaction of the precursor prochloraz with manganese chloride during the dilution process before use. Since the active ingredient content is at the spraying concentration, the content is relatively low, approximately 0.01-0.02 g / liter of water (for example, the active ingredient dosage of prochloraz manganese salt is 20 g / mu, and the sprayer uses 100-200 liters / mu of water, with mu being 1 / 15 hectare, and the same applies hereinafter). The stability of the nano-suspension dispersion of prochloraz manganese salt is adjusted by controlling the dosage of polymer additives. The dosage of polymer additives is related to the amount of prochloraz manganese salt generated by the system and the amount of water used for dilution. For example, if the dilution water dosage of prochloraz manganese salt is 100 kg, 150 kg, and 200 kg, respectively, the concentrations of the active ingredient are 0.02%, 0.013%, and 0.01%, respectively. The concentration of the polymer additive is at least in the range of 0.1% to 0.2%. Testing has shown that the active ingredient particles in the prochloraz manganese salt nanosuspension are approximately 10 to 50 nm in size. This nanosuspension remains stable for less than 8 hours, without precipitation or settling, and can be directly applied to various pesticide spraying equipment.

[0081] (5) The nano-suspension dispersion of prochloraz manganese salt and the nano-particles of prochloraz manganese salt are formed by reaction during the dilution and mixing process. This not only eliminates the need for the synthesis and purification process of the pesticide raw material factory to prepare prochloraz manganese salt from prochloraz, but also eliminates the need for the multi-step physical processing process of the pesticide formulation factory to process prochloraz manganese salt and other adjuvants into a wettable powder. The solution proposed by the present invention shortens the manufacturing process of the formulation and is directly applicable to plant protection in agricultural production. The process is environmentally friendly and energy-saving, and can significantly reduce production costs. The particle size of the nano-suspension dispersion of prochloraz manganese salt obtained by the present invention is less than 100 nm, which can fully exert the efficacy of the drug, reduce the amount of pesticide used, and play a role in reducing the amount and increasing the efficiency.

[0082] The key technologies of the present invention lie in the following aspects:

[0083] 1. The formation process of nanosuspension dispersion

[0084] This invention innovatively proposes a new model and method for preparing a nanosuspension from the water- and organic solvent-insoluble pesticide prochloraz manganese salt containing polyvalent metal ions. By utilizing the dilution process required for pesticide spraying, the pesticide precursor is mixed with the corresponding metal salt. By leveraging the rapid nature of ionic reactions, the reactant concentration and stirring speed are controlled to produce a nanosuspension dispersion with a crystal size of less than 100 nanometers. This method eliminates the chemical synthesis and purification steps required by prochloraz manganese salt manufacturers to prepare it from prochloraz, as well as the multi-step processing steps required by pesticide formulation manufacturers to convert the prochloraz manganese salt technical into a wettable powder. This model and method are the most important key technologies of this invention and are also suitable for compounding prochloraz manganese salt with other pesticides to prepare nanosuspensions.

[0085] 2. Dilution water volume

[0086] After the amount of component A and component B is fixed, the dilution water amount is one of the key technologies for controlling the dilution concentration of the two components to obtain nanoscale prochloraz manganese salt microparticles. The dilution water amount determines the reaction of the reactants in the dilution liquid and the concentration of the product. If the water amount is too little, such as 2kg, the concentration of the reactants in the dilution liquid is relatively large, the concentration of the generated nanoparticles is high, and the stability time of the particle size below 100nm is short. If the water amount exceeds 300kg, although a transparent dilution liquid can still be obtained, the concentration of the auxiliary agent contained in the components is significantly reduced, and the stability of the nano suspension will also deteriorate unless the amount of the auxiliary agent is increased. Thus, after the amount of component A and component B is fixed, the appropriate dilution water amount, for example, a water amount range greater than 5kg and less than 300kg, is one of the key technologies for controlling the concentration of the two components and generating a stable prochloraz manganese salt nano suspension dispersion.

[0087] 3. Types and dosage of additives

[0088] Selecting and using the appropriate type and dosage of additives is another key technology for producing nano-suspensions of prochloraz manganese salt. However, when prochloraz and manganese salt are combined in water to form prochloraz manganese salt nanoparticles, the dispersion effect of large amounts of water and stirring alone cannot stabilize the resulting nano-sized prochloraz manganese salt particles. This is because the particles are not static; they are constantly undergoing Brownian motion, colliding with each other. As a result of these collisions, the particles merge, grow, and eventually precipitate. An effective way to prevent the size of the generated particles from increasing is to select the appropriate type of water-soluble polymer additive (also called a dispersant) and determine its dosage to ensure that the resulting nanoparticles are evenly dispersed in the aqueous solution of the polymer dispersant. This type of dispersant is primarily a water-soluble polymer that is soluble in water. The microscopic state of water-soluble polymers in water is typically the form of random coils. The size of these random coils is generally larger than the newly formed prochloraz manganese salt particles, depending on the molecular weight and concentration of the polymer additive. If the nanoparticles of prochloraz manganese salt generated at this time are smaller than 100nm or even smaller than 50nm, these particles can enter the interior of the random coils, preventing and slowing the mutual collisions between the particles, thereby improving the stability of the generated nanoparticles. This is the dispersing, suspending and stabilizing effect of adding additives.

[0089] The present invention has tested a variety of different types of water-soluble polymers. Among the numerous anionic, cationic, and nonionic surfactants, only nonionic polymer additives can currently achieve the desired effect, such as fatty alcohol polyoxyethylene ethers, fatty acid polyoxyethylene ethers, alkylaryl polyoxypropylene polyoxyethylene ethers, castor oil polyoxyethylene ethers, Tween-80, and alkyl polyglycosides. In most cases, anionic surfactants react with manganese ions to form a water-insoluble precipitate, which loses the dispersing effect. However, the present invention does not exclude the special case where appropriate anionic and cationic surfactants are optimized in combination with each other or with nonionic surfactants to achieve a water-soluble and non-precipitated state.

[0090] The type and amount of the water-soluble polymer additive used in the present invention can be determined through experimentation. The criteria for determination are as follows: first, the resulting prochloraz manganese salt nanosuspension must be transparent, water-soluble, and have a particle size of less than 100 nm; second, the transparent nanosuspension must be stable for at least 2 to 5 hours.

[0091] The amount of the adjuvant used in the present invention is affected by the amount of dilution water. A larger amount of dilution water is used, the amount of the adjuvant used will be appropriately increased. The ratio of the adjuvant to the amount of dilution water is at least within 1:1200, preferably within 1:1000, and more preferably within 1:800.

[0092] 4. Type and dosage of solvent

[0093] The selection of the aqueous solvent is also one of the key technologies of the present invention. The solvent is selected based on the solubility of prochloraz. Prochloraz is easily soluble in a variety of organic solvents, such as toluene, dichloromethane, dimethyl sulfoxide, acetone, methanol, isopropanol, ethyl acetate, cyclohexanone, etc., with a solubility greater than 600g / L.

[0094] Considering the toxicity and cost of the solvent, acetone, dimethyl sulfoxide, isopropyl alcohol, ethyl acetate, and cyclohexanone are preferred. More preferably, acetone, isopropyl alcohol, ethyl acetate, and cyclohexanone are selected. Among these, acetone and isopropyl alcohol are water-soluble solvents, while ethyl acetate and cyclohexanone are water-insoluble solvents.

[0095] For example, prochloraz is dissolved in acetone as component A, manganese chloride as component B, and a water-soluble polymer additive as component C. Component C is first dissolved in dilution water, and then component B is added to form a mixed aqueous solution. Once component A is added to the mixed aqueous solution, the acetone solvent dissolves in water and rapidly disperses into the aqueous phase. The dissolved prochloraz molecules precipitate in the aqueous phase and immediately react with manganese ions in the water to form prochloraz manganese salt molecules. These prochloraz manganese salt molecules are insoluble in water and aggregate to form crystal nuclei, which then grow into grains. Under stirring, the grains entrap the random coils or micelles formed by the polymer additive, dispersing and stabilizing them. By controlling the rate of addition of component A and the intensity of the stirring and dispersion, a suspension of prochloraz manganese nanoparticles can be obtained.

[0096] The above-mentioned prochloraz solution uses only a water-soluble acetone solvent, which is insufficient in controlling the nanometer size of the product. This is because, once component A enters the aqueous phase, all the acetone rapidly dissolves in water, and the prochloraz dissolved by it will all precipitate out in the aqueous phase. If the amount added cannot be evenly controlled, the product precipitation may be too concentrated, which is detrimental to controlling the nanometer size of the manganese prochloraz. To address this problem, the present invention uses a combination of a water-soluble solvent and a water-insoluble solvent to remedy this deficiency. Two solvents, one water-soluble and one water-insoluble (such as acetone and cyclohexanone), are used to dissolve the prochloraz. When the solution is added to an aqueous solution containing manganese chloride, the water-soluble acetone rapidly disperses into the aqueous phase, causing a portion of the prochloraz dissolved by it to precipitate out in the aqueous phase, while the prochloraz dissolved by the water-insoluble cyclohexanone solvent continues to exist in the solution. Under the action of a polymer auxiliary agent and stirring, this solution may begin to form micelles. As stirring continues, once the polymeric additive contained in Component A is evenly dispersed in the aqueous phase, the additive concentration decreases, the micellar structure may no longer exist, and the prochloraz molecules dissolved in the water-immiscible cyclohexanone solvent will gradually precipitate in the aqueous phase. Thus, with the same amount of Component A added, the process of prochloraz entering the aqueous phase becomes longer and slower, thus facilitating the production of a stable dispersion of the prochloraz manganese salt nanosuspension.

[0097] The relative ratio between the water-soluble solvent and the water-insoluble solvent depends on the specific type of solvent and the experimental results.

[0098] 5. Adding method and stirring method

[0099] The method of adding ingredients is also a key factor influencing the performance of prochloraz manganese salt nanosuspensions. Once the dilution water volume and the ratio between components A and B are determined, how the mixing process is performed will affect the resulting particle size and stability. For example, the method of adding the three components raises the following questions:

[0100] First, during the dilution process, should component C or component B be added to the dilution water first?

[0101] Second, how is component A added to the mixed aqueous solution of components B and C? Is it added by pouring, adding in a trickle, dropping, or spraying? Is it added at a single point or multiple points? Is it added continuously or intermittently? And so on.

[0102] In reality, once the addition method is determined, the question of stirring method also arises. Similarly, stirring methods vary, such as manual or mechanical stirring? Single-point stirring or multi-point stirring? Continuous stirring or intermittent stirring? The stirring method is closely related to the stirring speed.

[0103] Whether it's the method of addition, stirring, or speed, these factors all hinge on the concentration of the reactants in the reaction zone formed instantly upon mixing the two dilute components, and the ability to rapidly disperse the products. The most direct way to assess the effectiveness of these two methods and stirring speeds is to observe the transparency of the resulting product. If the resulting nanosuspension is clear and transparent, and exhibits a prolonged stability, this indicates an appropriate method of addition and an effective stirring method and speed.

[0104] Preparation method of prochloraz manganese salt nano suspension

[0105] The present invention adopts the following technical solutions:

[0106] Under the condition that the stirring speed is not less than the effective stirring speed, component A is added to the mixed diluted aqueous solution formed by component B and component C to form a nano-suspension dispersion of prochloraz manganese salt.

[0107] Components B and C form a mixed aqueous solution with dilution water, and the optimal addition order is selected to obtain a transparent mixed diluted aqueous solution.

[0108] Component A, a solution of prochloraz dissolved in acetone or a mixture of acetone and cyclohexanone, is added to the above mixed diluted aqueous solution under controlled conditions.

[0109] The adding method, adding speed and stirring speed are controlled so that 100 nm nano-crystals of prochloraz manganese salt are generated in the suspension, that is, a 100 nm nano-suspension dispersion of prochloraz manganese salt.

[0110] Effective stirring speed

[0111] The so-called effective stirring speed refers to the process in which when one component is added to another component, the nanopesticide crystals generated in the mixed liquid can be dispersed in time by stirring at a speed not less than the effective stirring speed, without significant crystal aggregation, thus preventing the size of these crystals from increasing to hundreds of nanometers or micrometers.

[0112] Stirring method

[0113] Mechanical stirring: In the field, such conditions are ideal. Large stirring equipment generally does not exceed 100 rpm, and the specific stirring speed can be adjusted within this stirring rate. However, obtaining large containers with stirring devices in the field is often difficult.

[0114] Manual stirring: This is more suitable for most application scenarios. In this case, the stirring speed must meet the physiological requirements of manual stirring and cannot be too fast.

[0115] For manual stirring, the stirring speed should be consistent with the human body's physiological function. To obtain a stable target product, the material addition rate can be appropriately reduced. The material addition rate can be determined by observing the product's transparent state in the system.

[0116] Joining method and joining speed

[0117] To ensure that the added materials are uniformly fine and quickly dispersed upon entering the system, one component can be added to another continuously, intermittently, or dropwise. For dropwise addition, spraying with a manual sprayer, commonly available in rural areas, is the most effective method. The addition speed is determined by observing the transparency of the product within the system.

[0118] Existing pesticide formulations, which use water as a dispersion medium for spraying, typically require dilution or mixing of co-used pesticide formulations before spraying, a process commonly known as "tank mixing." The present invention utilizes this "tank mixing" process to mix components A, B, and C according to a specific addition method and rate in the presence of a specific water-soluble polymer adjuvant, thereby directly producing a transparent "tank-mixed" nano-suspension dispersion of prochloraz manganese salt that can be sprayed on-site.

[0119] Dilution water consumption

[0120] Current experimental data indicates that around 5 kg is a reasonable starting range. This dilution water consumption is strongly correlated with our target stabilization period. This is a multivariate issue, and the additive content and composition of the components also play a role.

[0121] The present invention aims to produce a suspension of prochloraz manganese salt with a transparent stability period of 2 to 5 hours at a size below 100 nm. When the unit mass of precursor (e.g., 20 grams of prochloraz) and the mass of manganese chloride reacted with it are fixed, factors that can affect the nanoparticle size and stability include the amount of dilution water, the amount of additives used, and the preparation method.

[0122] The amount of water used for dilution can affect the size of the generated nano-manganese salt of prochloraz crystals and the length of the stable period. The reason is that the amount of water used as a dispersion medium will affect the concentration of the prochloraz solution and the manganese chloride solution at the moment of contact reaction, as well as the uniformity of dispersion, and therefore will also affect the number of crystal nuclei generated, the size of the crystals, the dispersion effect of the crystals, and the chances of crystal aggregation and growth. The amount of additives used affects the concentration of its aqueous solution in different water amounts, as well as the size of its dispersion, suspension and stabilization effect on the generated nano-crystals and the length of the stable period. Too little water will produce a limit. For example, when the dilution water amount is 2 kg or less (drone spraying), it is difficult to generate a transparent suspension dispersion of manganese salt of prochloraz. Therefore, it is necessary to increase the amount of water used for dilution.

[0123] The present invention produces 20 grams of the target product, i.e., a prochloraz manganese salt suspension with a transparent stability period of 2 to 5 hours at a level below 100 nm. Depending on the type of crops to be sprayed, the amount of water used for dilution is selected to be between 5 and 300 kilograms, preferably in the range of 50 to 200 kilograms.

[0124] [Implementation Method]

[0125] The method of the present invention for preparing a nano-suspension dispersion of prochloraz manganese salt with a size of less than 100 nm, taking three components as an example, comprises the following steps:

[0126] In the first step, a water-soluble polymer additive (as component C) is dissolved in the dilution water to form a transparent dilution aqueous solution.

[0127] In the second step, manganese chloride solid or its aqueous solution (as component B) is added into the transparent diluted aqueous solution and dissolved to form a transparent mixed diluted aqueous solution.

[0128] The third step is to uniformly add component A to the transparent mixed diluted aqueous solution under mechanical stirring (preferably) or manual stirring conditions at a stirring speed not less than the effective stirring speed in accordance with a certain adding method (continuous or intermittent pouring, dropping, spraying, etc.).

[0129] Here are some examples:

[0130] Example 1.

[0131] Prochloraz manganese salt suspension dispersion can be used to prevent and control cucumber anthracnose and tobacco brown spot disease. The dosage of active ingredient is 20 g / mu.

[0132] The dilution water volume is 20 kg.

[0133] The dosage of each component, the amount of dilution water, and the preparation of the solution are listed in the table below:

[0134] How to do it:

[0135] (1) In a suitable container, add 20 kg of dilution water. Add component C in sequence, stir and dissolve to obtain a transparent aqueous solution of the water-soluble polymer additive.

[0136] (2) Add component B to the aqueous solution of the water-soluble polymer auxiliary agent, stir and disperse to obtain a transparent mixed diluted aqueous solution of component B and component C.

[0137] ⑶ While stirring, continuously add component A dropwise to the transparent mixed diluted aqueous solution of component B and component C. Control the addition speed and stirring speed to keep the system transparent until the solution is completely added.

[0138] The obtained transparent nano-suspension dispersion of prochloraz manganese salt can be directly used for spraying operations and has a stable time of 3.5 hours.

[0139] Example 2.

[0140] Myclobutanil manganese salt suspension dispersion can be used to prevent and control grape black pox disease. The dosage of active ingredient is 50 grams per mu, and the dilution water volume is 200 kilograms.

[0141] The dosage of each component, the amount of dilution water, and the preparation of the solution are listed in the table below:

[0142] How to do it:

[0143] (1) In a suitable container, add 200 kg of dilution water. Add component C in sequence, stir and dissolve to obtain a transparent aqueous solution of the water-soluble polymer additive.

[0144] (2) Add component B to the transparent aqueous solution of the water-soluble polymer auxiliary agent, stir and disperse, and obtain a transparent mixed diluted aqueous solution of component B and component C.

[0145] (3) While stirring, add component A in a continuous stream to the transparent mixed diluted aqueous solution of components B and C. Control the addition speed and stirring speed to keep the system transparent until the solution is completely added.

[0146] (4) The obtained transparent manganese nano-suspension dispersion of prochloraz can be directly used for spraying. The stability time is 5 hours.

[0147] Example 3.

[0148] Myclobutanil manganese salt suspension dispersion can be used to prevent and control anthracnose of citrus. The dosage of active ingredient is 60 grams per mu, and the dilution water volume is 250 kilograms.

[0149] The dosage of each component, the amount of dilution water, and the preparation of the solution are listed in the table below:

[0150] How to do it:

[0151] (1) In a suitable container, add 240 kg of dilution water. Add component A and stir to disperse it to obtain a transparent prochloraz nano-diluted emulsion.

[0152] ⑵Dissolve component B in 10 kg of water to obtain a diluted solution of component B.

[0153] (3) While stirring, continuously add the diluted solution of component B to the diluted emulsion of component A. Control the addition speed and stirring speed to keep the system transparent until the solution is completely added.

[0154] (4) The obtained transparent nano-suspension dispersion of prochloraz manganese salt can be directly used for spraying. The stability time is 5 hours.

[0155] Example 4.

[0156] Myclobutanil manganese salt suspension dispersion can be used to prevent and control rice blast and rice false smut. The dosage of active ingredient is 15 grams per mu and the dilution water dosage is 15 kilograms.

[0157] The dosage of each component, the amount of dilution water, and the preparation of the solution are listed in the table below:

[0158] How to do it:

[0159] (1) In a suitable container, add 14 kg of dilution water. Add component C in sequence, stir and dissolve to obtain a transparent aqueous solution of the water-soluble polymer additive.

[0160] (2) Add component B to 1 kg of water and stir to dissolve. Then add it to the transparent aqueous solution of the water-soluble polymer additive, stir, disperse and dissolve to obtain a transparent mixed diluted aqueous solution of component B and component C.

[0161] ⑶ While stirring, add component A dropwise to the transparent mixed diluted aqueous solution of component B and component C. Control the addition speed and stirring speed to keep the system transparent until the solution is completely added.

[0162] (4) The obtained transparent manganese nano-suspension dispersion of prochloraz can be directly used for spraying. The stability time is 4.5 hours.

Claims

1. A nano suspension of prochloraz manganese salt, characterized in that: The prochloraz manganese salt nano suspension refers to a prochloraz manganese salt nano suspension of less than 100 nanometers; the prochloraz manganese salt nano suspension of less than 100 nanometers is formed by diluting and mixing three components with water: Component A: a solution of prochloraz dissolved in at least one ketone solvent; Component B: manganese chloride solid or manganese chloride aqueous solution; Component C: A mixture consisting of at least one water-soluble polymer auxiliary agent.

2. The prochloraz manganese salt nano suspension according to claim 1, characterized in that The component C is added with diluting water to form a transparent aqueous solution.

3. The prochloraz manganese salt nano suspension according to claim 1, characterized in that The water-soluble polymer auxiliary agent is a non-ionic surfactant.

4. The prochloraz manganese salt nano suspension according to claim 3, characterized in that The nonionic surfactant is at least one of the following options: water-soluble starch, water-soluble cellulose, water-soluble guar gum and its derivatives, polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymer, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, alkylphenol polyoxyethylene ether, arylphenol polyoxyethylene ether, castor oil polyoxyethylene ether, alkyl polysaccharide, Tween, polyvinyl alcohol, polyvinyl pyrrolidone; preferably, polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymer, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, arylphenol polyoxyethylene ether, castor oil polyoxyethylene ether, alkyl polysaccharide, Tween.

5. The prochloraz manganese salt nano suspension according to claim 1, characterized in that The nano suspension of prochloraz manganese salt with a size below 100 nanometers has a stable period of hours.

6. The prochloraz manganese salt nano suspension according to claim 1, characterized in that The ratio of the amount of the water-soluble polymer additive to the amount of dilution water is not greater than 1:1200.

7. The prochloraz manganese salt nano suspension according to claim 1, characterized in that The ketone solvent is acetone, cyclohexanone, isopropanol, ethyl acetate, or a mixture thereof.

8. The prochloraz manganese salt nanosuspension according to any one of claims 1 to 7, characterized in that The mass ratio of prochloraz: manganese chloride is in the range of: Prochloraz: manganese chloride = 100: 8-10; Preferably, prochloraz:manganese chloride=100:8-9.

9. A method for preparing a nano suspension of prochloraz manganese salt, comprising adding component A to a mixed diluted aqueous solution formed by component B and component C under a stirring speed not less than an effective stirring speed to form a nano suspension dispersion of prochloraz manganese salt: Component A: a solution of prochloraz dissolved in at least one ketone solvent; Component B: manganese chloride solid or manganese chloride aqueous solution; Component C: A mixture consisting of at least one water-soluble polymer auxiliary agent.

10. The preparation method according to claim 9, characterized in that: The method of adding one component to another component is one of the following four methods: continuous addition, intermittent addition, dropwise addition, and spray addition.

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