WO2024131349A1

WO2024131349A1 - Nano suspension specially for downy mildew

Info

Publication number: WO2024131349A1
Application number: PCT/CN2023/129260
Authority: WO
Inventors: 张子勇; 梁冰
Original assignee: 张子勇
Priority date: 2022-12-18
Filing date: 2023-11-02
Publication date: 2024-06-27
Also published as: WO2024131345A1; WO2024131343A1; WO2024131344A1; WO2024131338A1; WO2024131342A1; WO2024131340A1; WO2024131347A2; WO2024130462A1; WO2024131341A1; WO2024131336A1; WO2024131333A1; WO2024131339A1; WO2024131346A1; WO2024131335A1; WO2024131350A1; WO2024131337A1; WO2024131348A1

Abstract

The present invention relates to the field of nano pesticides, and relates to a propineb nano suspension having a particle size less than 100 nm and a preparation method therefor. According to the present invention, a propineb nano suspension having a size less than 100 nm is formed by diluting two or three components with water and mixing same. The preparation method comprises: under the condition that a stirring speed is not less than an effective stirring speed, adding a first-component dilution solution into a second-component dilution solution, or adding a second-component dilution solution into a first-component dilution solution; and forming a propineb compound nano suspension.

Description

Nano suspension for downy mildew

[Technical field]

The invention belongs to the field of nano pesticides, and particularly relates to the preparation of a binary or ternary composite nano suspension of propineb with particle size less than 100 nanometers.

【Background technique】

Improving the efficacy of pesticides is one of the important ways to reduce the amount of pesticides, and developing nanopesticides is the best way. Nanopesticides originated at the beginning of this century. They use nanotechnology to reduce the size of particles in pesticide formulations and achieve nano-dispersion. Nano (nm) is a unit of length. 1 nanometer is one billionth of a meter and one millionth of a millimeter. Simply put, nanopesticides refer to pesticide formulations in which the size of pesticide particles is at the nanometer level during application. From the perspective of application effect and stability, the particle size is preferably less than 100nm and the smaller the better. At present, the particle size of traditional pesticide formulations is above micrometers. If it is reduced to the corresponding nano size, the particle size is reduced by 1,000 times, then the number of particles can theoretically increase by 1 billion times and the surface area can increase by 1,000 times. This is the reason for the development of nanopesticides.

Propineb is a broad-spectrum carbamate protective organic sulfur fungicide developed by Bayer, Germany. It is also another large-scale product after Propineb. Because the molecule does not contain manganese ions, the molecular structure is different from other mancozeb varieties. The poisonous group has a methyl group, the hydrophobicity of the molecule is enhanced, and the biological activity is improved. This unique molecular structure and bactericidal characteristics make it difficult to produce resistance. Propineb also has common characteristics with other mancozeb series fungicides. They are all preventive protective fungicides, but Propineb has a wider bactericidal spectrum, more stable efficacy, and better bactericidal effect. The mechanism of action is to selectively act on the synthesis of fungal cell walls and proteins, inhibit the infection and germination of spores, and inhibit the growth of mycelium, causing its deformation and death. In addition, Propineb contains zinc that is easily absorbed by crops, which is beneficial to promote crop growth and improve the quality of fruits.

The chemical name of propineb is poly-1,2-propylene (bis(dithiocarbamate) zinc). Its chemical structure is shown in formula (1). The pure product is a white powder with a slightly special odor, and it decomposes above the melting point of 150°C. Because it is a multivalent metal salt, its solubility in water and common organic solvents is extremely low. The solubility in water (20°C) is <0.01 g/L. Solubility in organic solvents (g/L): toluene, hexane and dichloromethane are all <0.1. Only dimethylformamide + dimethyl sulfoxide >200. It is stable under dry conditions and decomposes under moist, acidic and alkaline conditions.

Propineb is a protective fungicide that is both fast-acting and long-lasting, with the characteristics of a broad fungicide spectrum, good safety, and the function of micro-fertilizer.

It has a wide spectrum of fungicides: high efficacy against downy mildew, early blight, late blight, leaf spot, anthracnose, black spot, ring rot, etc., and can prevent and treat a variety of crop diseases such as leaf spot, Chinese cabbage downy mildew, cucumber downy mildew, tomato early blight, tomato late blight, grape downy mildew, etc.; good safety: long lasting effect, safe for crops, humans, livestock and other beneficial organisms, low-toxic fungicide, non-toxic to bees, harmless to users, can be used during flowering and various growth periods of crops. It also has the function of micro-fertilizer: Propineb can release zinc ions to supplement the zinc elements required for growth, so it has the effect of foliar fertilizer, which is beneficial to crop coloring and quality improvement. However, since Propineb is a protective fungicide, it must be sprayed before the disease occurs or at the onset. In order to enhance the therapeutic effect on the disease while protecting it, it is often used in combination with other fungicides in production.

Propineb kills conidia and developing conidia by contact. Crops, including fruit trees, tea trees, vegetables, flowers, Chinese medicinal materials, potatoes and rice, etc., to prevent and control a variety of diseases. Leaf spot, leaf spot, downy mildew, blight, anthracnose, rust and leaf spot are the best. It has a protective effect on rice and other zinc-sensitive crops. Bayer vigorously promotes and applies it in China under the trade name Antaishan (70% propineb wettable powder). At present, there are more than 50 pesticide companies in China that produce propineb single agent, the dosage form is mainly wettable powder, and some are water-dispersible granules. There are no less than 100 pesticide companies that produce compound preparations of propineb and other pesticides, the dosage form is the same as the single agent. Because the content of active ingredients in these preparations is too high, up to 70% to 80%, the space for adding dispersants and auxiliary components is limited, and the particles are in close contact, which makes it easy for the particles to aggregate and crystallize, and the particle size is larger.

However, whether used alone or in combination, propineb is insoluble in water or organic solvents due to the physical properties of its original drug, so the dosage forms are mainly traditional powders, wettable powders, water-dispersible granules, and suspensions. According to the existing pesticide preparation processing technology level, the minimum size of pesticide particles in its preparations is usually more than a few microns, and the largest is more than ten microns or even tens of microns. The large size of propineb pesticide particles is not conducive to the efficacy of the drug. In addition, a certain degree of drug resistance has been generated by years of large-scale use. The current usage per unit area is large, usually 750 grams to 2250 grams of active ingredients per hour ^m2 . In this way, how to improve its efficacy and reduce its usage per unit area? It has become an important content of the research on the formulation type of this pesticide variety.

It should be made clear that the preparation process of the existing single-dose dosage form of propineb is to first synthesize the original drug and then process the dosage form. The specific steps include: (1) Original drug synthesis . It is divided into two steps: the first step is to synthesize propineb acid with 1,2-propylenediamine and _CS2 , and then neutralize it with alkali to obtain propineb ammonium or propineb sodium or propineb potassium. The second step is to react propineb ammonium or propineb sodium or propineb potassium with zinc salt to obtain propineb. The propineb ammonium or propineb sodium or propineb potassium synthesized in the first step is water-soluble and can be dissolved in water. It then undergoes a metal ion exchange reaction with zinc salt to obtain block or granular precipitated propineb. The precipitated propineb is neither soluble in water nor in organic solvents, and needs to be separated, washed, and dried to obtain propineb original drug. (2) Preparation processing . The solid propineb original drug is used as the raw material to process the preparation. Usually, crushing, grinding, mixing and other processes are required to obtain the propineb preparation. The above-mentioned preparation process after propineb, propineb, sodium, or potassium requires the addition of corresponding production equipment and workshops, such as filters, dryers, crushers, grinders, mixers, and corresponding production processes and processing techniques. It can be found that the process from synthesizing water-soluble propineb, propineb, sodium, or potassium to processing into a solid dosage form of propineb is long and energy-consuming.

Prior art: Chinese invention patent CN201711490378.4 “Preparation method of nano mancozeb” discloses a nano mancozeb powder dosage form.

The traditional process flow of preparing mancozeb technical and processing it into wettable powder is shown in Figure 1.

[Summary of the invention]

Prior applications: PCT/CN2022/139831; PCT/CN2022/139832; PCT/CN2022/139833

One of the purposes of the above invention is to overcome the shortcomings of the prior art and provide a new idea and method for preparing a mancozeb powder dosage form that is different from the prior art. Through the dilution process with water, the reaction of mancozeb (or mancozeb, mancozeb potassium) with manganese salt and zinc salt is achieved to generate mancozeb, thereby providing a mancozeb nano suspension that is apparently water-soluble and transparent in appearance, and is directly used for spraying.

The mancozeb nano suspension described in the above invention can be loaded into a pesticide spraying device for spraying.

The innovative ideas of the present invention are as follows:

Propionate ammonium or propionate sodium or propionate potassium is a water-soluble ammonium salt, which is a single molecule dispersed in water as one component. The zinc salt that reacts with it is also a single molecule and metal ion dispersed in water as another component. When the two meet, it is very easy to form The structure of propineb is formed. Since zinc ions are multivalent metal ions, in addition to the commonly believed salt structure, the propineb formed may actually be a complex structure. Since it is an ionic reaction, the reaction speed is fast. When mixing, by controlling the addition speed and stirring speed of a certain component, the generated propineb nanoparticles can be obtained.

Under the condition of controllable stirring speed, an aqueous solution of one component (such as zinc salt) is added to an aqueous solution of another component (such as propineb). By controlling the dropping speed and stirring speed, nano-crystals of propineb can be generated, and a nano-suspension of propineb can be generated.

The generated propineb nanoparticles can temporarily and stably exist in water when they are very small in size and few in number. As propineb nanoparticles are continuously generated, the system will experience collision, growth and aggregation of propineb nanoparticles. When the size of propineb nanoparticles approaches the wavelength of visible light, or even exceeds it, the system begins to show opalescence and gradually becomes opaque. In addition, due to the effect of the grains' own gravity, large-sized grains are precipitated. In order to prevent this phenomenon, polymer additives must be added to the system. Polymer additives are water-soluble polymers, usually non-crystalline polymers, which exist in the form of random coils after dissolving in water. Random coils are loose spherical structures formed by the spontaneous curling of water-soluble polymer chains. The internal aggregates are lipophilic and hydrophobic molecular main chains, and the external ones are hydrophilic polar groups. At this time, when the size of the propineb nanoparticles generated by the system is less than 100 nanometers, under the shear force of mechanical stirring, these water-insoluble propineb nanoparticles will be dispersed into the interior of the random coils and loaded by the random coils, thereby isolating and preventing the effective collision, crystal growth, precipitation and precipitation of the grains. Therefore, the random coils formed by the water-soluble polymer additives play a role in dispersing, suspending, stabilizing and protecting the propineb nanoparticles. Since the random coils are uniformly dispersed in the water phase, the propineb nanoparticles uniformly dispersed in the random coils are also uniformly dispersed in the water phase. When the size of the grains is below 100 nanometers, natural light will not be significantly reflected or refracted when passing through this solution, so the system looks clear and transparent and apparently water-soluble.

It should be pointed out that in the process of generating nano-pesticide crystals, the dripping speed of one of the two components of propineb to the other component and the stirring speed of the aqueous solution of the polymer additive involve the amount of reactants added to the aqueous phase per unit time and the degree of uniform dispersion of the product, which is an important factor affecting the size of the generated nano-pesticide crystals. For the dripping speed, if the target is that the size of the precipitated nano-pesticide crystals is less than 100 nanometers, then whether the system is clear and transparent is the criterion. Its theoretical basis is that when the particle size is less than one-fourth of the lower limit of the wavelength of visible light, no serious refraction and reflection will be formed, so the system is transparent. The wavelength of visible light is 400 to 760 nanometers, and less than one-fourth is less than 100 nanometers. Conversely, if the system for generating nano-pesticide crystals is clear and transparent, it means that the size of the generated crystals is less than 100 nanometers.

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

① The mixing speed of the two-component solution (i.e. the speed of adding one of the components) cannot be too fast. If the solution is added too quickly, the two components will be unevenly dispersed, and the local concentration will be too high. Then the speed of generating grains will also be fast, and the number of generated grains will also be large. Aggregation between nano-crystals may occur, thus increasing the grain size. If the system has opalescence, it means that the grain size is already several hundred nanometers. If the opalescence becomes more and more severe or even opaque, it means that the grain size is close to or exceeds one micron. Therefore, the adding speed should be based on keeping the system transparent.

② The stirring speed of the system should be appropriately increased. The stirring speed of the system is related to the generation speed and dispersion speed of propineb nanoparticles in the water phase. The more fully stirred and the better the dispersion, the more conducive it is to the rapid formation, dispersion and entry of nanoparticles into random coils, so that smaller-sized grains remain in a stable dispersed state and avoid aggregation between grains. In this way, it is possible to obtain smaller and uniform propineb nanoparticles. When the two-component solution is added, it is necessary to continue stirring for a while to ensure the dispersion, suspension and stability of the generated propineb nanoparticles in the water-soluble polymer additive.

Explanation of terms

Tyndall phenomenon: The so-called Tyndall phenomenon refers to the fact that when a beam of light passes through a colloid, the colloid can be observed from the direction perpendicular to the incident light. A bright "pathway" appears in the liquid, and this phenomenon is also called the Tyndall effect. The essence of the Tyndall effect is a scattering phenomenon when light propagates in a colloid. The reason for this phenomenon is mainly because the particle size of the colloid particles is between 1 and 100 nm. When visible light passes through the colloid, it will produce a more obvious scattering effect, while the scattering effect of the true solution on light is very weak. Colloids have obvious Tyndall phenomenon, while true solutions with dispersed molecules have almost no such phenomenon, so it is often used to distinguish between colloidal solutions and true solutions.

If the particle is smaller than the wavelength of the incident light, light scattering occurs, and the light wave radiates around the particle, which is called scattered light or opalescence. The Tyndall effect is essentially a light scattering phenomenon or opalescence phenomenon. The scattering effect of a true solution on light is very weak. The intensity of scattered light also increases with the increase of 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 100nm, and the Tyndall phenomenon may occur. If the particle is larger than the wavelength of the incident light (400nm~740nm), light reflection occurs obviously. When the solution shows increasingly heavier opalescence, turbid liquid or even opaque, the particle size has increased to close to micrometers or above.

System: The so-called system refers to the suspension system formed by mixing two components under the premise of controlling the addition speed and stirring when preparing the propineb nano suspension in the present invention. The system is the target product - nano suspension generated by mixing water, precursor, zinc salt and water-soluble polymer additive.

Component: A component refers to a composition containing one or more ingredients. In principle, any ingredient used in the present invention can form a component alone, but considering the convenience of packaging, transportation and use, the components should be combined and simplified. The principles are: ① The components do not react with each other; ② The number of components formed by the components should not be too large.

Ingredients: The so-called ingredients refer to the raw materials used in the present invention, including water-soluble propionate salt, zinc salt, water-soluble polymer auxiliary agent and water.

Precursor: The so-called precursor refers to the parent substance used in the production reaction of the target product propineb, that is, water-soluble propineb salts, including propineb ammonium, propineb sodium, and propineb potassium.

Water-soluble polymer additives: refers to polymer substances that contain hydrophilic polar groups in the macromolecule and can dissolve in water, also known as polymer surfactants, active agents, and additives. Water-soluble polymer additives can play a role in dispersion, suspension, emulsification and stabilization. According to the nature of the group, they can be divided into anionic, cationic, zwitterionic and non-ionic polymer additives.

Particle size: also known as particle size; refers to the size of the propineb crystals formed by the interaction of the precursor with the zinc salt under the dispersion of the water-soluble polymer additive in the system, and 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.

Below 100 nanometers: It is a statistical classification of the size of pesticide particles in the system. The sizes of all pesticide particles in the suspension present a statistical distribution. The nano suspension below 100 nanometers described in the present invention refers to the peak value of the particle size distribution curve of the mass fraction of each fraction of the particle classification and its corresponding size is less than 100 nanometers. It can be detected by the British Malvern laser nanoparticle size analyzer and processed by the Number statistical method.

Stable period: refers to the stable time that the nanosuspension can maintain a transparent state after preparation. In order to ensure the completion of the spraying operation, the stable period should be no less than 1 hour. The hour-level stable period proposed in the present invention refers to a stable time between 1 and 5 hours.

Effective stirring speed: The so-called effective stirring speed refers to the fact that when one component is added to another component in a certain way, the nano-crystals generated in the system can be dispersed in time through stirring at a speed not less than the effective stirring speed, without the growth and aggregation of the grains, and the grain size does not increase to the level of several hundred nanometers. The transparent state of the generated liquid in the system is a sign of effective stirring.

Effective stirring: The addition of components and the stirring method and speed have an important impact on the system liquid. The stirring methods include mechanical stirring, multi-point mechanical stirring, manual stirring, and multi-point manual stirring. Fast stirring speed is conducive to producing good results. If the system liquid is transparent, it is considered to be effectively stirred. Otherwise, it is considered to be ineffective stirring.

Addition method: The so-called addition method includes adding component A to component B, component B to component A, or adding component A and component B to the system at the same time, and also includes continuous addition, intermittent addition, trickle addition, drop addition, spray addition, and addition at a fixed position or a moving position, etc. The best addition method is to mix and disperse the two components as quickly as possible.

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

Nanoemulsion: also known as nanoemulsion. It refers to a dispersion system in which the active ingredients of pesticides are dispersed in water to form nano-sized latex particles. The appearance of nanoemulsion is clear and transparent, the particle size is usually below 100nm, and it has thermodynamic stability.

Metalaxyl-M nanoemulsion: also known as Metalaxyl-M nanoemulsion.

Metalaxyl/pyraclostrobin nanoemulsion: contains a nanoemulsion of two fungicides.

Metalaxyl-M/Propamocarb hydrochloride nanoemulsion: sometimes also described as a composite nanoemulsion of metalaxyl-M and propamocarb hydrochloride, in which case propamocarb hydrochloride is dissolved in the aqueous phase of the emulsion.

Binary compound of propineb and metalaxyl-M

Propineb is a protective fungicide, and its main function is to prevent the occurrence of fungal diseases. In order to achieve the best control effect, it should be used in advance and preferably mixed with other fungicides, especially systemic fungicides. Therefore, in order to improve the control effect of crop diseases, propineb is often compounded with other fungicides and/or insecticides. In order to improve the control effect of propineb, the present invention proposes to further obtain a binary compounded nano suspension of propineb and a plurality of different fungicides on the basis of the technology of obtaining propineb nano suspension. The method and scheme proposed in the present invention can make the compounded nano suspension of propineb more widely used.

Propineb has a strong compounding property and can be compounded with up to 21 fungicide ingredients to form a variety of compound preparations, which can further enhance the fungicide spectrum and scope of action. At present, the registered dosage forms are mainly traditional wettable powders and water-dispersible granules, and the particle size is above the micron level. The registered crops are mainly apples, cucumbers, potatoes, tomatoes, grapes, rice, watermelons and other crops, and the main diseases controlled are leaf spot disease, downy mildew, anthracnose, early blight, late blight and other diseases of the subphylum Mastozotocin, subphylum Ascomycota and subphylum Deuteromycota.

Metalaxyl-M is a fungal protein synthesis inhibitor. It mainly inhibits the synthesis of ribosomal RNA in pathogenic fungi, prevents fungal spore production and inhibits hyphae growth, resulting in the lack of nutrients for pathogens, which cannot grow, develop and reproduce normally, thus leading to the death of pathogens. It has protective, therapeutic and systemic activities, especially the systemic ability that can be conducted up and down, and can be conducted laterally. It can pass through the seed coat and be conducted to various parts of the plant with seed germination and seedling growth. It can prevent and control various soil-borne and seed-borne diseases caused by low-level pathogens such as Pythium and Corytophthora in the Oomycetes. It is often used as a seed treatment agent in production. Because its water solubility is much higher than that of general fungicides. It has selective effects on downy mildew and phytophthora in the Oomycetes. For example, it has good control effects on potato/tomato late blight, grape/cucumber downy mildew, beet/watermelon/pepper blight, tobacco black shank, etc. It can also be used for the prevention and control of damping-off disease of various crops such as cotton and corn stem base rot.

The main application crops of metalaxyl include wheat, peanuts, corn, vegetables, beans, potatoes, sunflowers, litchi trees, grapes, cotton, lawns, ginseng and codonopsis Chinese medicinal materials, etc.

Preparation of binary compound of propineb and metalaxyl-M

According to the existing registration certificate of propineb/metalaxyl binary compound, its control target, dosage and reference dosage of the present invention are as follows:

(1) Target: Tomato late blight

40% (35% + 5%), control of tomato late blight, 80-100 g/mu, effective ingredient dosage per mu: 28-35 g of propineb + 4-5 g of metalaxyl-M - reference dosage for this invention

(2) Target: Potato late blight

56% (50% + 6%), control of potato late blight, 35-50 g/mu, effective ingredient dosage per mu: 17.5-25 g of propineb + 2.1-3 g of metalaxyl-M - reference dosage for this invention

(3) Target of control: cucumber downy mildew

50% (42% + 8%), control cucumber downy mildew, 60-80 g/mu, effective ingredient dosage per mu: 25.2-33.6 g of propineb + 4.8-6.4 g of metalaxyl-M - reference dosage for this invention

Preparation of a ternary compound of propineb and metalaxyl/pyraclostrobin

Pyraclostrobin is a methoxyacrylate fungicide that inhibits mitochondrial respiration, leading to cell death, and has protective, therapeutic, and leaf permeation conduction effects. It is mainly used to prevent and treat a variety of diseases caused by fungi on crops, and has good control effects on wheat powdery mildew and fusarium head blight. In addition to its direct effect on pathogens, pyraclostrobin can also induce physiological phenomena in many crops, especially cereals, such as increasing nitrogen absorption, thereby promoting rapid growth of crops and increasing crop yields, thereby achieving the goal of high crop yields.

The three-way combination of propineb/metalaxyl-M/pyraclostrobin has the functions of protecting, treating and enhancing leaf penetration and conduction. It has a long lasting effect. When used in the early stage of the disease, it can effectively prevent the invasion of pathogens and improve plant immunity, reducing the number of disease outbreaks and the number of medications. It is effective against most fungal diseases, including downy mildew, leaf spot disease, early blight, anthracnose, powdery mildew, black spot, rust, leaf spot, etc.

Propineb/Metalaxyl-M/Pyraclostrobin, used for the prevention and treatment of grape downy mildew, reference dosage of active ingredients per mu: Propineb 10-20, Metalaxyl-M 1.5-2, Pyraclostrobin 1.5-2 - reference dosage for this invention

Preparation of a ternary compound of propineb and metalaxyl/propamocarb hydrochloride

Felocarb hydrochloride is a low-toxic broad-spectrum fungicide with local systemic effect. It has both protective and therapeutic effects and belongs to the carbamate class. It inhibits mycelial growth, sporangium formation and spore germination by inhibiting the biochemical synthesis of phospholipids and fatty acids in the cell membrane of pathogens. It has special effects on oomycetes and diseases caused by algae-like fungi. It has good control effects on vegetable downy mildew, blight, damping-off disease, Solanaceae late blight, cotton blight, Cruciferae white rust, etc. It is suitable for liquid surface spray, seed treatment and soil treatment.

Propineb/metalaxyl/promocarb hydrochloride are used to control cucumber downy mildew. The dosage of active ingredients per mu is: 40-60 of propineb, 4-8 of metalaxyl, and 6.5-13 of promocarb hydrochloride, which are reference dosages used in the present invention.

The binary or ternary composite nano suspension of propineb and metalaxyl-M described in the present invention refers to a nano suspension of less than 100 nanometers; the binary or ternary composite nano suspension of propineb and metalaxyl-M described below 100 nanometers is formed by diluting and mixing at least two components with water:

Ternary composite nano suspension of propineb, metalaxyl-M and pyraclostrobin

The prior application (PCT/CN2022/139833) has described the nanosuspension of mancozeb and metalaxyl-methyl compound. On this basis, the present invention adopts propineb to add metalaxyl-methyl and pyraclostrobin to form a nanosuspension of ternary pesticides. Metalaxyl-methyl and pyraclostrobin are added to component A in the form of nanoemulsions, respectively. When the two components are mixed under certain conditions, the existence form of metalaxyl-methyl and pyraclostrobin particles depends on the amount of dilution water and the amount of polymer additives in the system. When the amount of water is small, the amount of diluted polymer additives can continue to maintain the existence of nanomicelles. At this time, propineb nanocrystals, metalaxyl-methyl and pyraclostrobin nanomicelles coexist. If the amount of water added is insufficient to maintain the minimum concentration of polymer adjuvants required for the nano-particles, the micelles will disappear, and metalaxyl-M and pyraclostrobin will precipitate in the water in the form of nano-crystals, becoming a mixture of nano-crystals of three pesticide active ingredients, or a mixture of nano-crystals generated by mixing two pesticide active ingredients, coexisting in the nano-suspension.

Ternary composite nanosuspension of propineb, metalaxyl-M, and propamocarb hydrochloride

The prior application (PCT/CN2022/139833) has described the nanosuspension of mancozeb and metalaxyl-M. On this basis, the present invention uses propineb to add metalaxyl-M and propamocarb hydrochloride to form a nanosuspension of a ternary pesticide. Metalaxyl-M and propamocarb hydrochloride are added to component A in the form of a nanoemulsion and a solution, respectively. When the two components are mixed under certain conditions, the microparticles of metalaxyl-M and propamocarb hydrochloride exist in the form of a nanoemulsion and a solution, respectively. When the two components are mixed under certain conditions, the microparticles of metalaxyl-M and propamocarb hydrochloride depend on the amount of dilution water and the amount of polymer additives in the system. When the amount of water is small, the amount of diluted polymer additives can continue to maintain the existence of nanomicelles. At this time, propineb nanocrystals and metalaxyl-M nanomicelles coexist. And propamocarb hydrochloride is dispersed in water as a single molecule. If the amount of water added is insufficient to maintain the minimum concentration of polymer adjuvants required for the nano-particles, the micelles will disappear, and metalaxyl-M will precipitate in the water in the form of nano-crystals, together with the nano-crystals generated by propineb, to become a mixture of nano-crystals of the two pesticide active ingredients, or a mixture of nano-crystals generated by the mixing of the two pesticide active ingredients, coexisting in the nano-suspension; while propamocarb hydrochloride will dissolve in the diluted water.

Binary composite nanosuspension of propineb and metalaxyl-M

The prior application (PCT/CN2022/139833) has described the nanosuspension of mancozeb and metalaxyl-M. On this basis, the present invention adopts propineb to add metalaxyl-M to form a nanosuspension of a two-component pesticide. Metalaxyl-M is added to component A in the form of a nanoemulsion. When the two components are mixed under certain conditions, the existence form of the metalaxyl-M particles depends on the amount of dilution water and the amount of polymer adjuvant in the system. When the amount of water is small, the amount of diluted polymer adjuvant can continue to maintain the existence of nano micelles. At this time, propineb nanoparticles and metalaxyl-M nanoparticles coexist. If the amount of water added is not enough to maintain the minimum concentration of polymer adjuvant required for the nanoparticles, the micelles will disappear, and metalaxyl-M will precipitate in the water in the form of nanocrystals, becoming a mixture of nanocrystals of two pesticide active ingredients, or a mixture of nanocrystals generated by mixing two pesticide active ingredients, coexisting in the nanosuspension.

The two-component regimen is as follows:

Component A: water-soluble propionate salt or water-soluble propionate salt aqueous solution, water-soluble polymer auxiliary agent; the water-soluble propionate salt is one of propionammonium, propionate sodium, propionate potassium, or a mixture of at least two of them; the water-soluble polymer auxiliary agent is a composite auxiliary agent composed of at least one non-ionic surfactant or its aqueous solution;

At the same time, metalaxyl nanoemulsion is added to component A (binary solution)

Alternatively, metalaxyl/pyraclostrobin nanoemulsion is added to component A (one of the three-component solutions)

Alternatively, metalaxyl/promocarb hydrochloride nanoemulsion is added to component A (second of the three-component solution)

Component B: a zinc salt or an aqueous solution of a zinc salt in a certain mass ratio; the zinc salt is a constituent substance of at least one salt;

The component B may be a solid mixture of zinc salts, or may be an aqueous solution formed by adding water, and may further include a water-soluble polymer auxiliary agent.

The zinc salt is selected from at least one of zinc sulfate, zinc acetate, zinc chloride and zinc nitrate.

The water-soluble polymer auxiliary agent is at least one nonionic surfactant.

The amount of the water-soluble polymer additive includes the sum of the amounts of the polymer additives in component A and component B, and the ratio of the amount of the water-soluble polymer additive to the amount of dilution water is not greater than 1:1500, preferably not greater than 1:1200, and more preferably not greater than 1:1000.

The dilution water amount includes all the water in the system.

The nonionic surfactant may be selected from water-soluble starch and its derivatives, water-soluble guar gum and its derivatives, polyoxypropylene-polyoxyethylene block copolymers, alkyl aryl polyoxypropylene polyoxyethylene ethers, fatty alcohol polyoxyethylene ethers, fatty acid polyoxyethylene ethers, fatty amine polyoxyethylene ethers, castor oil polyoxyethylene ethers, tween, alkyl polysaccharides, polyvinyl alcohol, etc. Preferably, polyoxypropylene-polyoxyethylene block copolymers, alkyl aryl polyoxypropylene polyoxyethylene ethers, OP-10, fatty alcohol polyoxyethylene ethers, fatty acid polyoxyethylene ethers, castor oil polyoxyethylene ethers, tween, alkyl polysaccharides, etc.

Furthermore, the nano-suspension of propineb below 100 nanometers has a stable period of hours.

When the propionate salt and zinc salt are propionate ammonium and zinc sulfate respectively, propionate ammonium has two acid groups. Considering zinc ion as a divalent metal ion, it also has tetravalent coordination activity. The range of its molecular (molar) ratio is:

Propanol: Zinc sulfate = 1: 0.50 ~ 1.01

Preferably, propinephrine: zinc sulfate = 1: 0.90-1.00

In industrial production, the molar ratio of propineb: zinc sulfate is 1: 1.01. A slightly excessive amount of zinc sulfate is used to make the propineb react completely. It should be recognized that the zinc ion has a multi-valence property, which leads to the product propineb being insoluble in water and solvents, and it plays a role similar to that of a crosslinking agent. The present invention uses the reaction of propineb and zinc sulfate to complete during the dilution process. Excessive zinc ions are not conducive to the dispersion and stability of the generated propineb nanoparticles, so the present invention uses a molar ratio of zinc sulfate close to or equal to 1.

In order to reduce the packaging and transportation costs of the preparation, the specifications of each component of the preparation can be the same or different. In the specification of the zinc salt aqueous solution as component B, a certain amount of water-soluble polymer additive can be added, and the mass concentration of the added agent is preferably such that component B does not appear turbid, and is usually not higher than 10%.

Propineb nano suspension below 100nm

In order to improve the efficacy of nano-scale propineb, the present invention needs to reduce its particle size as much as possible. The original intention of studying nano-pesticides is to improve the efficacy of pesticides and reduce the amount of pesticides used. The particle size of traditional pesticide preparations is usually in the micron level. Reducing it to the corresponding nanometer size spans three orders of magnitude. When it is reduced to different orders of magnitude, the number of increased particles is also different. For example, the usual particle size of traditional preparations is reduced from 2μm to 200nm, 20nm, and 2nm respectively. In theory, the particle size is The number increases by 1000 (10 ³ ), 1 million (10 ⁶ ), and 1 billion (10 ⁹ ) times respectively. It can be seen that the different reductions in particle size and the different increases in particle number lead to different effects on the efficacy. Therefore, in order to improve the efficacy of nanopesticides, the size of its particles should be reduced as much as possible.

In order to further improve the efficacy of nano-scale propineb, the present invention hopes to reduce its particle size to below 100nm. This is based on two aspects. First, the size below 100nm is the minimum size that a nano material must have in any one dimension. Second, the pesticide particles are between 1 and 100nm, and the preparation belongs to a colloidal solution, which is apparently water-soluble and clear in appearance. When a beam of light shines on the solution, a beam of light with a clear boundary can be seen, which meets the description of the "Tyndall" phenomenon.

Concentration of suspension

For suspensions with low concentrations, the number of particles below 100 nm is relatively large, which has little effect on transparency. This is the case for a system with a dosage of 1500 g/ha of propineb diluted with more than 50 kg of water.

For highly concentrated suspensions, the number of particles below 100 nanometers is relatively small, which will have a greater impact on transparency. For a system with a dosage of 1500 g/hectare of propineb, diluted with less than 20 kg of water, although the suspension can also be transparent, the concentration of particles is high, and the result of mutual collision will cause the nanocrystals to grow and even aggregate, which will significantly affect the transparency stability of the suspension.

The situation where the water consumption is between 20 and 50 kg is the transition period of the suspension concentration.

stable period

The binary or ternary (with pyraclostrobin or propamocarb hydrochloride) composite nano suspension of propineb and metalaxyl prepared by the present invention is a kind of transparent and water-soluble solution, but it is not a thermodynamically stable solution. Therefore, the time for the nano propineb suspension to maintain a transparent state is not infinite, but there is a stable period. Considering the operating characteristics of the spraying operation, after the nano propineb suspension is prepared, the required operating time should be at least more than 1 hour, so the length of the stable period can be described in hours. Therefore, the present invention proposes the concept of "stable period" for nano-level propineb suspensions below 100nm. That is, the propineb suspension below 100nm prepared by the present invention completes the spraying operation within the period when the solution remains transparent, and the stable period should reach at least 1 hour.

From the application perspective, the stable period can be further divided into four time periods: less than 1 hour, 1 to 5 hours, 5 to 10 hours, and more than 10 hours.

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

Hourly Stability Period

From the perspective of spraying operations:

The stabilization time is about 1 hour, which is not enough for the spraying operation; multi-component nanosuspensions with a stability period of more than 5 hours are difficult to achieve and unnecessary.

The stabilization time is between 2 and 5 hours, and the spraying operation of most pesticide equipment can be completed easily within this time.

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

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

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

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

Composition and additives of nano suspension of propineb and metalaxyl-M

Traditional propineb single-dose preparations and binary compound preparations are usually only one component and can be sprayed after being diluted with water, but the particle size of most pesticides is above the micron level. In order to obtain a nano-level propineb suspension, the present invention adopts at least two components and dilutes it with water according to a certain method to obtain a propineb suspension below 100 nanometers.

Two-component solution

Nano suspension of propineb and metalaxyl-M with a size below 100 nanometers has a stable period of hours and is a system generated by the mixed reaction of two components. They are:

Component A: It is composed of propineb, propineb sodium or propineb potassium solid or its aqueous solution, metalaxyl-M nanoemulsion and water to form a transparent aqueous solution. Among them, the precursor of propineb, the water-soluble polymer surfactant and water that play the role of dispersion, suspension and stabilization are the basic components of component A. On this basis, the nanoemulsion of the active ingredient can be added.

In component A, the metalaxyl-M nanoemulsion contains a certain amount of water-soluble polymer additives. As required, further water-soluble polymer additives may be added.

Component B is a system of a zinc salt mixture composed of a certain proportion, and the system has three forms: solid inorganic zinc salt (component B ₁ ), aqueous solution of inorganic zinc salt (component B ₂ ), and aqueous solution composed of inorganic zinc salt and water-soluble polymer additive (component B ₃ ).

Since the solubility of inorganic zinc salts in water is limited, the amount of water used needs to be limited in order to minimize the capacity of component B. In addition, the solubility of inorganic salts is also affected by the amount of additives, which also limits the amount of water-soluble polymer additives added to component B.

_B3 is an improved solution, which is to distribute the water-soluble polymer additive to both component A and component B. In view of several limitations of component B, there is an upper limit to the proportion of the water-soluble polymer additive in component B, unless the limitation of component B to a certain capacity is not considered.

Proportion of components for the production of Propineb

The above two-component improvement solution includes two components:

Component A: Use propinephrine (or propinephrine sodium, propinephrine potassium), or an aqueous solution of propinephrine (propinephrine sodium, propinephrine potassium), and then add an auxiliary agent.

Component B: Dissolve zinc sulfate (or zinc acetate, zinc chloride, zinc nitrate) in water in a certain proportion; auxiliary agents may be added.

In component A and component B, the amount of active ingredients is the basis for determining the composition of the two components. Propinenium (or propine sodium, propine potassium) in component A is the precursor for the formation of nano propineb and is the basis for determining the composition of component B.

The present invention takes the case that 100 grams of propineb is required to be sprayed on 1/15 hectare of field as an example, and a two-component design is carried out based on the generation of 100 grams of propineb suspension below 100nm.

Component A requires propinephrine or propinephrine sodium, propinephrine potassium, preferably propinephrine as a precursor, about 90 grams. According to the aforementioned distribution principle of the auxiliary agent in component A and component B, most of the auxiliary agent will be distributed in component A. If both component A and component B are packaged in 500 grams of mass, the amount of water used is the amount after removing propinephrine and auxiliary agents.

Component B, first determine the amount of inorganic zinc salt required for the reaction with propionium, the present invention preferably uses zinc sulfate. It is generally believed that zinc ions react with propionium to replace ammonium ions to form salts, generating a linear repeating structure or complex structure, and zinc ions also have a tetravalent coordination ability and may also form a complex structure.

Existing literature shows that in the synthesis process of propineb, the molecular (molar) ratio between propineb and zinc ion is 1:1.00-1.05. Propineb has two ammonium acid groups, and zinc ion is a divalent metal ion. The molecular molar ratio should be 1:1, and a slight excess is to ensure complete reaction. Although zinc ion also has a tetravalent coordination property, elemental analysis of propineb samples found that the zinc content was close to the theoretical value of 22.8%, indicating that propineb (propylene bis dithiocarbamate) and zinc sulfate are combined in a 1:1 ratio.

In the present invention, when the mass of the precursor propineb is 90 grams (0.346 mole, generating 100 grams of propineb), the zinc salt used is zinc sulfate (anhydrate), and the mass of the same mole is 56.5 grams, and a mass slightly lower than this can also be used.

Proportion of ingredients for the nano suspension of propineb and metalaxyl

The two-component solution includes two active ingredients: propineb and metalaxyl-M

Component A: Use propinephrine, propinephrine sodium or propinephrine potassium solid or its aqueous solution, or an aqueous solution of a mixture of at least two of them, add metalaxyl-M nanoemulsion, and then continue to add auxiliary agents.

Component B: Dissolve zinc sulfate (or zinc acetate, zinc chloride, zinc nitrate) in water in a certain proportion; additives may also be added.

In component A and component B, the amount of active ingredients is the basis for determining the composition of the two components. Propinenium, propineb, sodium or potassium propineb in component A is the precursor for the formation of nano propineb, which is the basis for determining the composition of component B.

Distribution of additives between component A and component B

The additives are mainly in component A.

Component A mainly contains propinephrine (or propine sodium, propine potassium) and metalaxyl-M nanoemulsion.

The reason why component A and component B must be packaged separately is that the two will react when mixed together. If a two-component method is used, the metalaxyl-M nanoemulsion in component A contains an additive, and an additive must be added separately, unless a third component of a separate additive is added. This makes the component and dilution process complicated. The condition for adding additives to component A is that both propenyl and the additive are soluble in water and can be miscible without precipitation and other unstable phenomena. However, considering that the content of propenyl and the additive is high and the viscosity itself is large, it is not easy to operate. Therefore, a certain amount of water should be added to dissolve and dilute it, reduce the viscosity, and facilitate operation. After achieving the above purpose, the amount of water added should reduce the total mass of component A as much as possible to reduce the production, packaging and transportation costs.

Component B is mainly zinc salt solid, or its aqueous solution, or its aqueous solution of polymer auxiliary agent.

Component B can be a solid mixture of zinc salts. It needs to be dissolved in water before mixing with component A. For convenience, their aqueous solutions can be used. Their solubility is limited and requires a large amount of water to dissolve. Depending on the solubility, you can choose to add or not add adjuvants. There are two reasons: First, if a large amount of adjuvants is added to component B, condensation and film formation will appear on the surface of the mixed solution of zinc salts, adjuvants and water, affecting the next step of operation; second, if the amount of adjuvants in component A can suspend and disperse the generated nanocrystals of propineb and metalaxyl, no adjuvants are required in component B. However, considering that it is used for disease and insect pest control in orchards, the amount of water used for spraying is large, usually up to 200 to 300 kg/mu. If the amount of adjuvants in component A is not enough to support the dispersion and suspension of the nanocrystals, it should be added to component B. Add appropriate additives. The premise is that the amount of additives added to the zinc salt aqueous solution should keep component B transparent and prevent the mixed solution from condensing into a film on the surface. The mass concentration of additives added to component B is generally not higher than 10%.

Although both component A and component B can solve the above difficulties by expanding their capacity, the increase in the dosage of the two components will undoubtedly increase the production, packaging and transportation costs. Taking these factors into consideration, it is important to balance the relationship between the dosage of each component and the product specifications and use as little adjuvant and water as possible under the premise of generating unit mass of propineb compound pesticide nanoparticles.

Water-soluble polymer additives

(1) The water-soluble polymer auxiliary agent with dispersing and suspending effects is an important component substance related to the size of the nano-crystals of propineb and metalaxyl-M generated when two or three components are diluted and mixed, as well as whether they can be stably dispersed and suspended.

⑵ Water-soluble polymer additives are polymer surfactants with properties such as dispersion, suspension, and viscosity improvement, which are derived from the hydrophobic chain structure and hydrophilic functional groups. These groups distributed in the end groups and side groups include hydroxyl, carboxyl, carboxymethyl, sulfonic acid, sulfate, phosphoric acid, amino, quaternary ammonium salt, etc. According to the source, they are divided into natural and synthetic polymers, and according to the nature of the hydrophilic group, they are divided into anionic, cationic, nonionic and zwitterionic polymers.

⑶ The principles for selecting water-soluble polymer additives in the present invention are: ① being able to stably disperse and suspend the generated pesticide nanoparticles; ② being unaffected by the reaction of multivalent metal ions with water-soluble mancozeb; ③ being as environmentally friendly as possible. Therefore, the present invention selects non-ionic polymer additives derived from natural substances. Such as polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers, various polyoxyethylene ethers with fatty alcohols, fatty acids, fatty amines, aromatic phenols, oil groups, etc. as hydrophobic groups, such as Peregram series, OP series, Tween series, polyol series, ricinoleic acid series, alkyl polysaccharides, etc. However, nonylphenol polyoxyethylene ethers with estrogenic toxicity should be abandoned.

(4) The nano suspension of propineb and metalaxyl-M is generated by the reaction of water-soluble propineb (or sodium) and zinc salt during the dilution and mixing process, and the latex particles or nano crystal particles are generated from the metalaxyl-M nanoemulsion.

The amount of polymer additives used is related to the amount of propineb/metalaxyl-M produced by the system and the amount of water used for dilution. The concentration of the polymer additives is at least in the range of 0.1% to 0.5%.

According to the test, the particle size of the propineb/metalaxyl nanosuspension is about 30-80nm. This nanosuspension can be in a stable state within 2-5 hours without precipitation or settling, and can be directly used in the spraying operation of various pesticide spraying equipment.

(5) The nano suspension of propineb and metalaxyl-M is mainly propineb nanoparticles, which are formed by reaction during the dilution and mixing process. Not only does it save the synthesis and purification process of preparing propineb original medicine from propineb ammonium or propineb sodium in the pesticide original medicine factory, but it also saves the multi-step physical processing process of processing propineb and other original medicines into wettable powders in the pesticide preparation factory. The solution proposed by the present invention can be directly applied to the plant protection link of agricultural production. The process is obviously energy-saving and environmentally friendly, and the production cost can be significantly reduced. A nano suspension dispersion with a particle size of propineb less than 100nm is obtained. The small-sized nanoparticles of the present invention can give full play to the efficacy of the medicine, significantly reduce the amount of pesticides used, and play a role of reducing the amount and increasing the efficiency in agricultural production.

FIG2 is a flow chart of preparing a nano suspension of propineb and metalaxyl-M by diluting with water in the present invention.

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

1. Nanosuspension generation process

The invention innovatively proposes a new mode and method for preparing nano suspensions from pesticides containing polyvalent metal ions that are insoluble in water and organic solvents. The precursor of the target product is mixed with the corresponding metal salt by utilizing the process that the pesticide needs to be diluted with water. The mixing and stirring speed of the reactants are controlled by utilizing the principle of rapid reaction of metal ions, thereby obtaining a nano suspension with a particle size of less than 100 nanometers for direct use. The method eliminates the chemical synthesis and purification process of the pesticide raw material factory preparing propineb from propineb ammonium or propineb sodium and propineb potassium, and also eliminates the multi-step physical processing process of the pesticide formulation factory processing propineb raw material into the existing dosage form wettable powder. This innovative research idea, preparation mode and method are the most important key technologies of the invention. This key technology is not only suitable for the occasions where propineb is compounded with other fungicides, but also suitable for the process of preparing nano suspensions from similar pesticide varieties.

2. Concentration of Propineb

The concentration of propineb generated by component A with propineb or propineb as the main component and component B with zinc salt as the main component in the diluted water is controlled. That is, if the dosage of the active ingredient propineb is 100 g/mu, the concentration of propineb generated by the reaction of propineb or propineb with zinc sulfate is affected by the amount of water used for dilution. For example, the concentration of propineb or propineb should be controlled in the range of 0.09-0.045 g/kg, the concentration of anhydrous zinc sulfate should be controlled in the range of 0.057-0.0028 g/kg, and the corresponding amount of water is 100 kg-200 kg. If the amount of water is too small, much less than 100 kg, for example, less than 20 kg, the size of the generated particles is large and the transparency of the diluted solution is poor. This is because the concentration of the particles is high, the probability of mutual collision to form larger particles increases, the stability decreases, and it is not conducive to the formation of particles below 100 nm. If the amount of water used exceeds 200 kg, although a transparent dilution can still be obtained, the concentration of the dispersant contained in the components is significantly reduced, and the stability of the diluted solution will also deteriorate. Therefore, controlling the concentration of the final Propineb, that is, controlling the amount of water used for dilution, is one of the key technologies for obtaining Propineb nanosuspension.

3. Dilution water volume

When the dosage of component A and component B is fixed, the dilution water consumption is one of the key technologies for controlling the dilution concentration of the two components, thereby obtaining a nano suspension of propineb and metalaxyl. The dilution water consumption determines the concentration of component A and component B. If the water consumption is too little, such as 20 kg, the concentration of component A and component B is large, the concentration of the generated nanoparticles is high, and the stable time of the particle size below 100nm is short. If the water consumption exceeds 300 kg, although a transparent dilution can still be obtained, the concentration of the auxiliary agent contained in the component is significantly reduced, and the stability of the nano suspension will also deteriorate, unless the dosage of the auxiliary agent is increased. Thus, when the dosage of component A and component B is fixed, for example, each component is 500 grams, the appropriate dilution water consumption, for example, a water consumption range of greater than 20 kg and less than 250 kg, is one of the key technologies for controlling the concentration of the two components and generating a stable nano suspension of propineb and metalaxyl.

4. Type and dosage of additives (dispersants)

Selecting the appropriate type and dosage of dispersant is another key technology for obtaining propineb nano suspension. However, when propineb ammonium or propineb sodium generates propineb particles with zinc salt in water, the dispersion effect of a large amount of water and stirring alone cannot keep the size of the newly generated propineb nanoparticles basically unchanged. This is because the particles dispersed in the water are not static, but are constantly moving and colliding with each other. As a result of the effective collision, the particles merge, crystallize and grow, and finally precipitate. An effective way to prevent the size of the generated particles from increasing is to select the appropriate type of dispersant and determine its appropriate dosage so that the nanoparticles of the active ingredient are evenly dispersed in the solution formed by the dispersant in water. This type of dispersant is first of all a water-soluble polymer that can be dissolved in water. The microscopic state of the water-soluble polymer in water is in the form of a random coil. The size of the random coil is much larger than the size of the newly generated propineb particles, depending on the size of the molecular weight and the dosage, usually in the hundreds of nanometers, and the largest can be greater than 1 micron. If the generated propineb nanoparticles are smaller than 100 nanometers, such as a few nanometers or a dozen nanometers, these particles can enter the interior of the random coils. To a certain extent, the random coils can prevent and slow down the mutual collisions between these particles, thereby improving the stability of the propineb nanoparticles. This is the role played by adding a dispersant.

But there is a problem here, water-soluble polymers have different types, whether all water-soluble polymers can be used. The present invention has tested a variety of different types of water-soluble polymers, and the conclusion obtained is negative. Among the numerous anionic surfactants, cationic surfactants and nonionic surfactants, only nonionic polymer additives can play the desired effect at present, such as alkyl alcohol, polyoxyethylene ether of alkyl acid, polyoxypropylene-polyoxyethylene ether of alkyl aryl, alkyl polysaccharide, castor oil polyoxyethylene ether, Tween-80, etc., and only a few of them have the best effect. The reason why anionic surfactants cannot be used is that the reaction mechanism of forming propineb in the process of dilution with water is essentially a process in which polyvalent metal ions replace ammonium ions or sodium ions to form salts or generate complexes. When the dispersant adopts anionic surfactants, the polyvalent metal ions may react in the same way as the sodium salt of the acidic group in the dispersant, so that the dispersant is precipitated together with the generated propineb nanoparticles from the state of being dissolved in water, and the dispersant cannot play the role of dispersion. The present invention does not exclude the special case where an individual cationic surfactant is optimally combined with an appropriate anionic or nonionic surfactant to dissolve in water without precipitation.

The important role of the water-soluble polymer auxiliary agent used in the present invention is self-evident. The present invention utilizes in the water dilution process, water-soluble propine ammonium or propine sodium or propine potassium, and zinc salts such as zinc sulfate that provide zinc ions, to mix in a certain manner, and through the reaction of zinc ions and propine ammonium or propine sodium or propine potassium in the mixing process, generate a propineb suspension of 100 nanometers or less. In the system, if it does not contain a surfactant, especially does not contain a water-soluble polymer surfactant, the nano crystal grains generated will constantly collide with each other, causing crystal growth and aggregation, until macroscopic precipitation occurs. When there is a water-soluble polymer surfactant of suitable type and consumption in the system, the nano crystal grains generated will enter the random coil formed by the water-soluble polymer auxiliary agent, just can stop and delay the collision and crystal growth between the nano crystal grains, thereby the generated propineb nano crystal grains are played a role of dispersion, suspension and stability.

The type and amount of the water-soluble polymer additive used in the present invention can be determined by experiments. The type of water-soluble polymer additive can be determined by conducting stability tests on different additives under fixed conditions and observing the effects. The additive type test includes a single dose of a water-soluble polymer additive or a compounded additive of two or more. The present invention will exemplify the types of different water-soluble polymer additives in the test examples. The determination of the amount of the water-soluble polymer additive will be based on meeting the following two conditions: First, the generated propineb nano suspension must be transparent in appearance and achieve apparent water solubility, so that the particle size can be guaranteed to be below 100nm; second, the stability time of this transparent nano suspension is between 1 and 10 hours, at least between 1 and 5 hours.

For the system generated by the mixed reaction of two components, the amount of adjuvant is distributed to component A and component B. Theoretically, if there is no capacity limit for the two components, the proportion of adjuvant in component A and component B can be arbitrarily distributed; if there is a packaging capacity limit for the two components, for example, for the use of the drug in 1/15 hectare of field (to generate 100 grams of propineb), component A and component B are specified to be 500 grams each. Considering that the amount of water used to dissolve the zinc salt in component B is large, and the inorganic salt solution has poor solubility for adjuvants, the amount of adjuvant added to component B will be greatly limited. In this way, the amount of adjuvant distributed to the two components can be determined by the following formula:

Amount of additives _{(component A)} = total amount of additives - amount of additives _{(component B)}

In the case of fixed capacity, the amount of additive added to component B can be determined by the situation after the additive is added to component B. When the system changes from transparent to turbid, it is the upper limit of the amount of additive added to component B.

The amount of the auxiliary agent used in the present invention is relative to the amount of water used for dilution. The amount of the auxiliary agent used will be appropriately increased if the amount of water used for dilution is large. The ratio of the amount of the auxiliary agent used to the amount of water used for dilution is at least within 1:1200, preferably within 1:1000.

5. Adding method and stirring method

The addition method is also one of the important factors affecting the performance of the nanosuspension of propineb and metalaxyl. When the amount of dilution water and the proportion of components A and B are determined, how to operate during the mixing process will affect the size and stability of the generated particles. For example, the addition method will involve the following issues:

First, is diluent X of component A added to diluent Y of component B, or is diluent Y of component B added to diluent X of component A?

Second, how to add? Is it pouring, trickle adding, dripping, or spraying? Is it single-point adding, or multi-point adding? Is it continuous adding, or intermittent adding? And so on.

In fact, after the addition method is determined, the stirring method will also be involved. Similarly, there are different ways of stirring, is it manual stirring or mechanical stirring? Is it single-point stirring or multi-point stirring? Is it continuous stirring or intermittent stirring? And so on. The stirring method is closely related to the stirring speed.

Regardless of the method of adding materials, stirring method, or stirring speed, they all involve the concentration of reactants in the reaction area formed at the moment of mixing the two-component dilutions and whether the products can be dispersed quickly. The most direct way to judge the standards of these two methods and stirring speed is to observe whether the products in the system are transparent. If the generated nanosuspension is clear and transparent, and has a long stable time, it means that the addition method is appropriate, and the stirring method and stirring speed are effective.

Preparation method of propineb and metalaxyl-M nano suspension

For the two-component solution, the present invention adopts the following technical solution:

Under the condition that the stirring speed is not less than the effective stirring speed, the component A dilution is added to the component B dilution, or the component B dilution is added to the component A dilution; a nano suspension of propineb and metalaxyl-M is generated.

Component A diluent and component B diluent are aqueous solutions formed by diluting component A and component B with water respectively;

Component A: composed of a water-soluble propionate salt or a water-soluble propionate salt aqueous solution and a water-soluble polymer auxiliary agent; the water-soluble propionate salt is one of propionammonium, propionate sodium, propionate potassium, or a mixture of at least two thereof;

Meanwhile, component A is added with metalaxyl nanoemulsion;

Component B: It is a zinc salt solid or its aqueous solution composed in a certain proportion.

The adding method, adding speed and stirring speed are controlled so that 100 nanometer-level nanocrystals of propineb and metalaxyl-M are generated in the suspension, and the final suspension is a 100 nanometer-level nanosuspension of propineb and metalaxyl-M.

Mixing method

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.

Mechanical stirring: In the field, it is difficult to have a large container with a stirring device. If such conditions are available, the speed of large stirring equipment generally does not exceed 100 rpm. Stirring at a speed close to this speed is sufficient.

For manual stirring, the stirring speed can be adjusted to the operating speed that is consistent with the physiological functions of the human body. In order to obtain a stable target product, the material addition speed can be appropriately reduced, and the material addition speed can be determined by observing the transparent state of the product in the system.

Joining method and joining speed

In order to make the added materials more uniform and fine, and disperse them quickly after entering the system, one component can be added to another component in a continuous, intermittent or dropwise manner. For the dropwise addition method, you can use the artificial sprayer commonly available in rural areas to spray and add, which has the best effect. The speed of addition is still determined by observing the transparent state of the product in the system to determine the speed of material addition.

For existing pesticide preparations, water is used as a dispersion medium for spraying. Usually, the pesticide preparation needs to be diluted with water before spraying, or the pesticide preparations used together need to be mixed together. This process is commonly known as "tank mixing". The present invention utilizes the "tank mixing" process to mix component A and component B at a certain concentration, a certain addition method and an addition speed under the action of a specific adjuvant, a dispersant, so as to directly obtain a "tank mixed" transparent propineb/metalaxyl-M nano suspension that can be sprayed on site.

Dilution water consumption

The current experimental data shows that 50 kg is a reasonable starting range. This dilution water consumption is strongly related to our target stable period. This is a multivariate problem, and the additive content and additive composition in the components are also influencing factors.

The purpose of the present invention is to obtain a nano suspension of propineb and metalaxyl-M with a transparent stability period of 2 to 5 hours at a level below 100 nanometers. When the unit mass of the precursor (for example, 90 grams of propineb and the metal salt (zinc sulfate) reacting therewith is fixed, and the mass of metalaxyl-M is also fixed, the factors that can affect the nano size and stability of the particles also include: the amount of dilution water, the amount of auxiliary agent used and the preparation method.

The amount of water used for dilution can affect the size of the generated nano-propineb grains 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 propineb solution and the zinc sulfate solution at the moment of contact reaction, as well as the uniformity of dispersion, and therefore will also affect the size of the generated grains, the dispersion effect of the grains, 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. If the amount of water used is too little, there will be a limit. For example, when the amount of water used for dilution is 20 kg or less, the stable time of the generated transparent propineb and metalaxyl nano suspension is about 1 hour, which cannot fully guarantee the spraying operation time. Therefore, it is necessary to increase the amount of water used for dilution.

The invention selects the dilution water amount between 30 and 300 kilograms, preferably between 50 and 200 kilograms, for generating 100 grams of the target product, i.e., a suspension of propineb and metalaxyl-M with a transparent stable period of 2 to 5 hours at a level below 100 nm.

Three-component basic scheme

The basic scheme of the nano-suspension of propineb and metalaxyl-M of the present invention, which is less than 100 nanometers, is a system formed by three components. They are:

Component A': It is composed of propinephrine, propinephrine sodium or propinephrine potassium solid or its aqueous solution, which is the precursor for generating propinephrine zinc nanoparticles.

Component A' can be propinephrine, propinephrine sodium, propinephrine potassium, or a mixture thereof. The single component or a mixture of two or three components can be solid, which is easy to package, small in size, and can be dissolved in water before use and dissolve quickly. However, its aqueous solution can also be used, which can be directly diluted to a certain volume with water before use. A certain amount of water-soluble polymer additives may or may not be added to component A'.

Component B': It is composed of a certain proportion of zinc salt solid or its aqueous solution, which is the multivalent metal ion required to generate propineb nanoparticles.

Component B' is a mixture of inorganic zinc salts in a certain proportion. The zinc salt is selected from at least one of zinc sulfate, zinc acetate, zinc chloride and zinc nitrate. Component B' can be solid, so that the packaging volume is small, or its aqueous solution can be used. Due to the limitation of their solubility, the solution volume is large, which is not conducive to storage and transportation, but convenient to use. A certain amount of water-soluble polymer additives may or may not be added to component B'.

Component C: Metalaxyl

Metalaxyl-M nanoemulsion is used as component C. Metalaxyl-M nanoemulsion contains a certain amount of water-soluble polymer additives. As required, water-soluble polymer additives may be added to component C or not.

The total mass of the water-soluble polymer additives required for the three-component solution is distributed among component A', component B' and component C, and is also included in the metalaxyl-M nanoemulsion in component C.

[Brief Description of the Figures]

Figure 1: a process flow chart of the traditional preparation of mancozeb technical and processing into wettable powder formulations;

Figure 2: Schematic diagram of the process for preparing a nano suspension of propineb and metalaxyl (two components)

Figure 3: Schematic diagram of the process for preparing a nano-suspension of propineb and metalaxyl (three components)

[Implementation Method]

The method for preparing a transparent nano-suspension of propineb and metalaxyl-M in a size below 100 nm according to the present invention comprises the following steps:

In the first step, component A and component B are diluted respectively according to different water amounts and different dilution ratios to form component A dilution liquid and component B dilution liquid.

The second step is to uniformly add the component A dilution to the component B dilution in a certain adding method (continuous or intermittent pouring, dropping, spraying, etc.) under mechanical stirring (preferably) or manual stirring conditions at a stirring speed not less than the effective stirring speed; or add in the reverse order.

The steps of the three-component scheme are as follows:

In the first step, component A' and component B' are diluted respectively according to different water amounts and different dilution ratios to form component A' dilution liquid and component B' dilution liquid.

The second step is to add component C into the diluted solution of component A’ and stir to disperse evenly.

The third step is to uniformly add the component A' and component C dilutions to the component B' dilution in a certain adding method (continuous or intermittent pouring, dropping, spraying, etc.) under mechanical stirring (preferred) or manual stirring conditions at a stirring speed not less than the effective stirring speed; or add in the reverse order.

For the three-component compounding solution, add pyraclostrobin or propamocarb hydrochloride to the two-component compounding of propineb/metalaxyl-M.

Here are some examples:

Example 1

Propineb/Metalaxyl-M nano suspension can be used to prevent and treat tomato late blight. The dosage of its active ingredients is 35/4 g/mu respectively, and the dilution water dosage for spraying tomatoes is 40 kg/mu. About 32 g of propineb is needed to produce 35 g of propineb.

Component ratio: The component ratio, dilution water volume, water volume distribution, addition sequence and method, and test results of each component are listed in the following table:

How to do it:

Component A and component B were diluted and dissolved in a ratio of 4/5 and 1/5 of 40 kg of water, respectively, to obtain component A dilution and component B dilution, respectively. Under manual stirring, the component B dilution was added to the component A dilution in a continuous stream to obtain a transparent nano-suspension of propineb/metalaxyl-M. The stability time was 4 hours.

Example 2

Propineb/Metalaxyl-M nano suspension can be used to prevent and treat potato late blight. The dosage of active ingredients is 25/3 g/mu respectively, and the dilution water dosage for spraying potatoes is 30 kg/mu. About 23 g of propineb is needed to produce 25 g of propineb.

How to do it:

Component A and component B were diluted and dissolved in the ratio of 2/3 and 1/3 of 30 kg of water, respectively, to obtain component A dilution and component B dilution, respectively. Under manual stirring, the component B dilution was added to the component A dilution by continuous spraying to obtain a transparent nano suspension of propineb/metalaxyl-M. The stable time was 3.5 hours.

Example 3

Propineb/Metalaxyl-M/ Pyraclostrobin nano suspension can be used to control grape downy mildew. The dosage of its active ingredients is 20/2/2 g/mu respectively, and the dilution water dosage for spraying grapes is 50 kg/mu. 18 g of propineb is needed to produce 20 g of propineb.

How to do it:

Component A and component B were diluted and dissolved in a ratio of 4/5 and 1/5 of 50 kg of water, respectively, to obtain a component A dilution and a component B dilution, respectively. Under manual stirring, the component B dilution was added to the component A dilution in a continuous dropwise manner to obtain a transparent nano suspension of propineb/metalaxyl-M/pyraclostrobin. The stable time was 5 hours.

Example 4

This embodiment is basically the same as the embodiment 3, but implements a three-component solution, which is different in the component composition, the type and amount of the auxiliary agent, and the order and method of adding the dilution water.

How to do it:

Component A' and component B' are diluted and dissolved in a ratio of 4/5 and 1/5 of 50 kg of water, respectively, to obtain component A' dilution and component B' dilution, respectively. Then component C is added to the component A' dilution to form a mixed dilution of component A' and component C. Under manual stirring, the component B' dilution is added to the mixed dilution of component A' and component C in a continuous spraying manner. A transparent nano suspension of propineb/metalaxyl/pyraclostrobin was obtained in the solution, and the stability time was 5 hours.

Example 4

Propineb/Metalaxyl/ Propamocarb hydrochloride nano suspension can be used to control cucumber downy mildew. The dosage of its active ingredients is 50/5/10 g/mu respectively, and the dilution water dosage for spraying cucumber is 30 kg/mu. 45 g of propineb is needed to produce 50 g of propineb.

How to do it:

Component A' and component B' were diluted and dissolved in a ratio of 4/5 and 1/5 of 30 kg of water, respectively, to obtain component A' dilution and component B' dilution, respectively. Component C was added to the A' dilution and stirred evenly to obtain a mixed dilution of component A' and component C. Under manual stirring, the component B' dilution was added to the mixed dilution of component A' and component C in a continuous spraying manner to obtain a transparent nano suspension of propineb/metalaxyl/promocarb hydrochloride. The stable time was 4 hours.

Claims

A nano suspension specifically for downy mildew; the nano suspension specifically for downy mildew is a nano suspension below 100 nanometers; the nano suspension below 100 nanometers is formed by diluting and mixing two components with water:

Component A: water-soluble propionate salt or water-soluble propionate salt aqueous solution, water-soluble polymer auxiliary agent; the water-soluble propionate salt is one of propionammonium, propionate sodium, propionate potassium, or a mixture of at least two thereof;

Component A is added with metalaxyl-M nanoemulsion, or metalaxyl-M/pyraclostrobin nanoemulsion, or metalaxyl-M/promocarb hydrochloride nanoemulsion;

Component B: It is composed of zinc salt or aqueous solution of zinc salt in a certain mass ratio; the zinc salt is a constituent substance of at least one salt.
The nanosuspension specifically for downy mildew as claimed in claim 1 is characterized in that the nanosuspension below 100 nanometers has a stable period of hours.
The nanosuspension for downy mildew as claimed in claim 1, characterized in that the component B is formed into an aqueous solution by adding a water-soluble polymer additive and water.
The nanosuspension specifically for downy mildew disease according to claim 1, characterized in that the water-soluble polymer auxiliary agent is a nonionic surfactant.
The nano suspension specially used for downy mildew disease according to claim 1 is characterized in that the ratio of the amount of the water-soluble polymer auxiliary agent to the amount of dilution water is not greater than 1:1200.
The nanosuspension for downy mildew as claimed in claim 4, characterized in that the nonionic surfactant is at least one of the following options: water-soluble starch and its derivatives, water-soluble guar gum and its derivatives, polyoxypropylene-polyoxyethylene block copolymers, alkyl aromatic polyoxypropylene polyoxyethylene ethers, OP-10, fatty alcohol polyoxyethylene ethers, fatty acid polyoxyethylene ethers, fatty amine polyoxyethylene ethers, castor oil polyoxyethylene ethers, Tween, alkyl polysaccharides, polyvinyl alcohol, polyvinyl pyrrolidone.
The nanosuspension for downy mildew according to any one of claims 1 to 6, characterized in that the zinc salt is selected from at least one of zinc sulfate, zinc acetate, zinc chloride and zinc nitrate.
The nano suspension for downy mildew as claimed in claim 7, characterized in that when the propionate and the zinc salt are propionate ammonium and zinc sulfate respectively, the range of their molecular molar ratio is:
Propionate: Zinc sulfate = 1: 0.50 ~ 1.01
Preferably, propinephrine:zinc sulfate=1:0.90-1.00.
A method for preparing a nano suspension for downy mildew as claimed in claims 1 to 8; adding a diluent of component A to a diluent of component B under the condition that the stirring speed is not less than the effective stirring speed; or adding a diluent of component B to a diluent of component A to form a binary composite nano suspension;

The component A dilution and the component B dilution are aqueous solutions formed by diluting component A and component B with water, respectively.
The preparation method according to claim 9 is characterized in that the way of adding one component to another component is one of the following four ways: continuous addition, intermittent addition, dropwise addition, and spray addition.