CN117794369A - Broad-spectrum nano suspension containing pyraclostrobin for preventing and treating fungal diseases - Google Patents

Abstract

The invention belongs to the field of nano pesticides, and relates to propineb nano suspension with particle size smaller than 100 nanometers and a preparation method thereof. The invention adopts two or three components to be diluted and mixed with water to form the propineb nano suspension with the size of below 100 nanometers. The preparation method comprises the following steps: adding the first component diluent to the second component diluent or adding the second component diluent to the first component diluent under the condition that the stirring speed is not less than the effective stirring speed; and forming the propineb compound nano suspension.

Description

Broad-spectrum nano suspension containing pyraclostrobin for preventing and treating fungal diseases

[ field of technology ]

The invention belongs to the field of nano pesticides, and particularly relates to preparation of propineb binary compound nano suspension with particle size smaller than 100 nanometers.

[ background Art ]

The improvement of the pesticide effect is one of important ways of pesticide decrement, and the development of nano pesticides is the best method. The nanometer pesticide is prepared through nanometer technology to reduce the particle size in pesticide preparation and realize nanometer dispersion. Nanometer (nm), which is a unit of length, 1 nanometer is one-billion meters, which is one-millionth of a millimeter. Briefly, a nano pesticide refers to a pesticide formulation in which the pesticide particle size is in the nano order in application. From the viewpoint of application effect and stability, the particle size is preferably less than 100nm and the smaller the better. At present, the particle size of the traditional pesticide preparation is above micrometers, if the particle size is reduced to the corresponding nanometer size, the particle size is reduced by 1000 times, the particle number can be theoretically increased by 10 hundred million times, and the surface area can be increased by 1000 times. This is why nano pesticides are developed.

Propineb (Propineb), a broad-spectrum carbamate protective organic sulfur bactericide developed by Bayer (Bayer) in germany, is also a large-scale product following Propineb. Because the molecule does not contain manganese ions, the molecular structure is different from other kinson varieties, a methyl group is added to the toxic and killing group, the hydrophobicity of the molecule is enhanced, the biological activity is improved, and the unique molecular structure and the sterilization characteristic make the bacterium unsuitable for generating resistance. The propineb and other zineb series bactericides have the common characteristics of being preventive protection bactericides, but the propineb has wider bactericidal spectrum, more stable drug effect and more excellent bactericidal effect. The action mechanism is to selectively act on the cell wall of fungi and the synthesis of protein, inhibit the infection and germination of spores, and inhibit the growth of mycelium, so that the mycelium is deformed and dead. In addition, propineb contains zinc element which is easy to be absorbed by crops, and is beneficial to promoting the growth of the crops and improving the quality of fruits.

The chemical name of propineb is poly-1, 2-propylene (zinc bis-dithiocarbamate). The chemical structural formula is shown in formula (1). The pure product is white powder with slightly special smell, and the melting point is above 150deg.C. The solubility in water and in common organic solvents is extremely low due to the multivalent metal salts. The solubility in water (20 ℃) is <0.01 g/L. Solubility in organic solvents (g/L): toluene, hexane dichloromethane were all <0.1. Only dimethylformamide + dimethylsulfoxide >200. Stable under dry conditions and decompose under humid, acidic, alkaline conditions.

Propineb is a protective bactericide with quick and lasting effects, and has the characteristics of wide sterilization spectrum, good safety, micro-fertilizer effect and the like.

It has wide bactericidal spectrum: the pesticide composition has high control effect on downy mildew, early blight, late blight, leaf spot disease, anthracnose, cladosporium cucumerinum, ring spot disease and the like, and can prevent and treat various crop diseases such as alternaria leaf spot disease, celery cabbage downy mildew, cucumber downy mildew, tomato early blight, tomato late blight, grape downy mildew and the like; the safety is good: long lasting period, safety to crops, people and animals and other beneficial organisms, no toxicity to bees, no harm to users, and can be used in the flowering period and various growth periods of crops. Has the functions of micro-fertilizer: the propineb can release zinc ions to supplement zinc elements required by growth, so that the propineb has the effect of foliar fertilizer, is beneficial to coloring crops and improves quality. However, since propineb is a protective bactericide, the pesticide must be sprayed before or during the initial period of occurrence of diseases, and in order to enhance the treatment effect on the diseases while protecting, the propineb is often compounded with other bactericides in production.

Propineb has a bactericidal effect by killing conidia and developing conidia by contact. Can be applied to most crops including fruit trees, tea trees, vegetables, flowers, chinese medicinal materials, potatoes, rice and the like, and can prevent and treat various diseases. Preferably leaf spot, alternaria leaf spot, downy mildew, phytophthora root rot, anthracnose, rust disease and leaf spot. Has protective effect on zinc-sensitive crops such as rice. Bayer company has been widely used in China under the trade name of antoshan (70% propineb wettable powder). At present, more than fifty pesticide enterprises produce propineb single dosage forms in China, wherein the dosage forms are mainly wettable powder, and the dosage forms are water dispersible granules respectively. More than hundred pesticide enterprises produce the compound preparation of propineb and other pesticides, and the dosage form is the same as that of a single dose. Because the content of the effective components in the preparations is too high and is up to 70-80%, the space for adding the dispersing agent and the auxiliary agent is limited, and the particles are closely contacted, so that the particles are easy to aggregate and crystallize, and the particle size is larger.

However, the propineb is used alone or in a compound way, and is not dissolved in water or an organic solvent due to the influence of the physical properties, so that the dosage forms of the propineb are mainly traditional powder, wettable powder, water dispersible granules and suspending agents. According to the existing pesticide preparation processing technology level, the minimum size of pesticide particles in the preparation is usually more than a few microns, and the size is tens of microns or even tens of microns. The propineb pesticide has large particle size, is not beneficial to the exertion of pesticide effect, and has certain drug resistance generated by using a large amount for many years, and the current use amount per unit area is large, and is usually 750-2250 g/hm of active ingredient ² . How does this increase its efficacy and decrease its usage per unit area? Is an important content for researching the type of the pesticide.

It is clear that the preparation of the existing propineb single dosage form is carried out on the basis of synthesizing the original medicine first and then processing the dosage form. The method comprises the following specific steps: (1)Synthesis of raw medicine. The method comprises the following two steps: the first step is to use 1, 2-propylene diamine and CS ₂ Synthesizing propineb acid, then neutralizing with alkali to form salt to obtain propineb or sodium or potassium propineb, and the second step is that the propineb or sodium or potassium propineb reacts with zinc salt to obtain propineb. The propineb or sodium propineb or potassium propineb synthesized in the first step is water-soluble, can be dissolved in water, and then is subjected to metal ion exchange reaction with zinc salt to obtain the block or granular precipitated propineb. The precipitated propineb is not dissolved in water or organic solvent, and is required to be separated, washed and dried to obtain the propineb original drug. (2) Adding the preparationWorker's work. The solid propineb raw material is used as a raw material to process the preparation. The propineb preparation is usually obtained by grinding, milling, mixing and the like. The preparation process from propineb or sodium or potassium propineb requires the addition of corresponding production equipment and workshops, such as filters, dryers, crushers, grinders, mixers, and corresponding production and processing processes. It has been found that the process from the synthesis of water-soluble propineb or sodium or potassium propineb to the processing into solid dosage forms of propineb is both lengthy and energy consuming.

The prior art comprises the following steps: chinese patent No. CN201711490378.4, nanometer Mancozeb preparation method, discloses a nanometer Mancozeb zinc powder preparation.

The traditional process flow for preparing the mancozeb technical and processing the mancozeb technical into wettable powder is shown in figure 1.

[ invention ]

The prior application: PCT/CN2022/139831; PCT/CN2022/139832; PCT/CN2022/139833

One of the purposes of the invention is to overcome the defects of the prior art, provide a new thought and method which are different from the prior art for preparing mancozeb zinc powder dosage forms, realize the reaction of mancozeb (or manb, potassium maneb) and manganese salt and zinc salt through the water dilution process, and generate mancozeb, thereby providing the mancozeb nano suspension with water-soluble appearance and transparent appearance, and directly use for spraying.

Said invention also provides a method for preparing said mancozeb nano suspension liquid, and the pesticide spraying equipment can be used for spraying operation.

The innovative idea of the invention is as follows:

propineb or sodium or potassium propineb is a water-soluble ammonium salt, which is a monomolecular dispersion in water as a component. The zinc salt reacted with it is also a single molecule and a dispersion of metal ions in water as another component. When the two meet, the propineb structure is very easy to form. Since zinc ions belong to polyvalent metal ions, the propineb formed may actually be a complex structure, except for the salt-forming structure which is generally considered. The ionic reaction has high reaction speed, and during mixing, the produced propineb nano-crystalline grains can be obtained by controlling the adding speed and stirring speed of a certain component.

An aqueous solution of one component (e.g., zinc salt) is added to an aqueous solution of another component (e.g., propineb) with a controlled rate of agitation. The dripping speed and the stirring speed are controlled, and nano crystal grains of propineb can be generated to generate the propineb nano suspension.

The produced propineb nano-crystalline particles, when the size is small and the amount is small, can exist in water temporarily and stably. Because the propineb nano particles are continuously generated, the system can collide, grow up and gather the propineb nano crystal grains. When the size of the propineb nano-crystalline grain approaches the wavelength of visible light and even exceeds the wavelength, the system starts to generate opalescence and becomes gradually opaque, and the effect of the gravity of the crystalline grain is added, so that the crystalline grain with large size is precipitated. In order to prevent this, polymeric auxiliaries must be added to the system. The polymeric auxiliary is a water-soluble polymer, usually an amorphous polymer, and exists in a random coil morphology after being dissolved in water. The random coil is a loose spherical structure formed by spontaneous curling of a water-soluble polymer chain, wherein the inside of the random coil is gathered into a lipophilic and hydrophobic molecular main chain, and the outside of the random coil is a hydrophilic polar group. At this time, when the size of the propineb nano-crystalline grains generated by the system is smaller than 100 nanometers, under the action of shearing force of mechanical stirring, the water-insoluble propineb nano-crystalline grains can be dispersed into random coils and loaded by the random coils, so that continuous effective collision, crystal growth, precipitation and precipitation of the crystalline grains are isolated and prevented. Therefore, the random coil formed by the water-soluble polymer auxiliary agent has the functions of dispersing, suspending, stabilizing and protecting the propineb nano-crystalline grains. Because the random coil is uniformly dispersed in the water phase, the propineb nano-crystalline grains uniformly dispersed in the random coil are also uniformly dispersed in the water phase. When the grain size is below 100 nanometers, natural light does not undergo obvious reflection and refraction when passing through the solution, so that the system looks clear and transparent and is apparent to be water-soluble.

It should be noted that in the process of forming nano pesticide crystal grains, the dropping speed of one component of the two components of propineb to the other component and the stirring speed of the aqueous solution of the polymer auxiliary agent are generated, and the amount of the aqueous phase reactant added in unit time and the uniform dispersion degree of the product are involved, which are important factors influencing the size of the nano crystal grains of the formed product. For the dropping speed, if the grain size of the precipitated nano pesticide is smaller than 100 nanometers, whether the system is clear and transparent is the judging standard. The theoretical basis is that when the particle size is less than a quarter of the lower limit of visible wavelength, no severe refraction and reflection are formed, and therefore the system is transparent. The wavelength of the visible light is 400-760 nanometers, and less than one fourth is less than 100 nanometers. Conversely, if the system that produced the nano pesticide crystals is clear and transparent, it is shown that the crystal size produced is less than 100 nanometers.

To achieve this, attention must be paid to the following:

(1) the mixing speed of the two-component solution (i.e. the addition speed of one of the components) cannot be too fast. Too fast addition, uneven dispersion of the two components and too high local concentration, the speed of the generated crystal grains is also fast, the number of the generated crystal grains is also large, and aggregation among the nano crystal grains is likely to occur, so that the crystal grain size is enlarged. If the system appears opalescent, indicating that the grain size is already a few hundred nanometers, opalescence becomes more and more severe and even opaque, indicating that the grain size is already near or exceeds one micron. Thus, the rate of addition is such that the system is always transparent.

(2) The stirring speed of the system is properly accelerated. The stirring speed of the system relates to the generation speed and the dispersion speed of the propineb nano-crystalline grains in the water phase. The stirring is sufficient, the better the dispersion is, the more favorable the rapid formation and dispersion of nano-crystalline grains and the random coils are entered, so that the crystalline grains with smaller size can keep a stable dispersion state, and the aggregation among the crystalline grains is avoided. In this way, it is possible to obtain propineb nano-crystalline grains of small and uniform size. When the two-component solution is added, stirring is continued for a while to ensure the dispersion, suspension and stability of the produced propineb nano-crystal grains in the water-soluble polymer auxiliary agent.

Interpretation of the terms

The tyndall phenomenon: the Tyndall phenomenon is a phenomenon that when a beam of light passes through a colloid, a bright "path" in the colloid is observed from the direction of normal incident light, and this phenomenon is also called Tyndall effect (Tyndall effect). The essence of the tyndall effect is a scattering phenomenon when light propagates in a colloid. This occurs mainly because the particle size of the colloidal particles is 1-100 nm, visible light is more significantly scattered when passing through the colloid, and the scattering effect of the true solution on light is very weak. Colloids have a distinct tyndall phenomenon, whereas true solutions with molecules dispersed are scarcely available, and are therefore often used to distinguish between colloidal solutions and true solutions.

If the particles are smaller than the wavelength of the incident light, scattering of the light occurs, and the light waves are emitted around the particles, which is called scattered light or opalescence. The tyndall effect is essentially a scattering phenomenon of light or opalescence phenomenon. The scattering effect of the true solution on light is weak. The intensity of the scattered light also increases with increasing concentration of particles in the dispersion. Thus, when the observed solution is clear and transparent, indicating that the particle size in the solution is less than 100nm, the tyndall phenomenon may occur. If the particles are larger than the wavelength of the incident light (400 nm to 740 nm), reflection of the light occurs significantly. As solutions show increasingly heavy opalescence and even opalescence, the particle size has increased to near microns or above.

The system comprises: the system refers to a suspension system formed by mixing two components under the premise of controlling the adding speed mode and stirring when preparing the propineb nano suspension. The system is a target product-nano suspension formed by mixing water, a precursor, zinc salt, a water-soluble polymer auxiliary agent and the like.

The components are as follows: by component is meant a composition comprising one or more ingredients. In principle, any one of the components used in the present invention may be formed as a single component, but the combination of the components should be simplified in view of convenience in packaging, transportation and use. The principle is as follows: (1) no reaction occurs between the components; (2) the amount of the component formed by the ingredients should not be excessive.

The components are as follows: the components are raw material materials used in the present invention, and include water-soluble propineb salt, zinc salt, water-soluble polymer auxiliary agent and water.

Precursor: the precursor means a precursor used in the reaction of producing the target product propineb, that is, a water-soluble propineb salt, including propineb, propineb sodium, and propineb potassium.

Water-soluble polymer auxiliary agent: the polymer is a polymer substance which contains hydrophilic polar groups in macromolecules and can be dissolved in water, and is also called a polymer surfactant, an active agent and an auxiliary agent. The water-soluble polymer auxiliary agent can play roles in dispersion, suspension, emulsification and stabilization. Depending on the nature of the groups, anionic, cationic, zwitterionic and nonionic polymeric auxiliaries can be distinguished.

Particle diameter of microparticles: also known as particle size; the precursor in the system is dispersed with water soluble polymer assistant to form propineb crystal grain size, which includes the grain size of other pesticide and has no specific microstructure.

The 100 nm scale is as follows: is a statistically significant classification of the size of pesticide particles in a system. All pesticide particle sizes in the suspension exhibit a statistical distribution. The nano suspension below 100 nanometers refers to a peak value on a particle size distribution curve of mass fraction of each fraction of particle classification and corresponding size of the particle is less than 100 nanometers. The detection can be carried out by using a British Markov laser nanometer particle size analyzer, and the processing is carried out by using a Number statistical method.

Stabilization period: refers to the stable time that the nanosuspension can maintain the transparent state after the preparation is completed. To ensure the completion of the spraying operation, the stabilization period should be not less than 1 hour. The invention provides an hour-level stabilization period, which means that the stabilization time is between 1 and 5 hours.

Effective stirring speed: the effective stirring speed refers to that when one component is added into the other component in a certain adding mode, nano crystal grains generated in the system can be timely dispersed through stirring at the stirring speed not smaller than the effective stirring speed, the growth and aggregation of the crystal grains do not occur, and the crystal grain size is not increased to hundreds of nanometers. The transparent state of the system liquid is an effective stirring sign.

And (3) effectively stirring: the mode and speed of adding components and stirring have important influence on the system generating liquid. The stirring mode comprises mechanical stirring, multipoint mechanical stirring, manual stirring and multipoint manual stirring. The stirring speed is high, and good effect is achieved. If the system-produced liquid is in a transparent state, efficient stirring is considered. Otherwise, the stirring is regarded as ineffective.

The adding mode is as follows: the addition mode includes adding the component A to the component B, adding the component B to the component A, or adding the component A and the component B to the system simultaneously, and also includes continuous addition, intermittent addition, trickle addition, dripping addition, spraying addition, fixed-position or mobile-position addition and the like. The two components are mixed and dispersed as soon as possible.

The addition rate is as follows: after the addition mode is determined, the addition amount of the components is controlled with the aim of realizing effective stirring.

Nanoemulsion: also known as nanoemulsions. The method is that a solution formed by the effective components of the pesticide forms a dispersion system of nano-sized emulsion particles under the action of an auxiliary agent dispersed in water. The nanoemulsion is clear and transparent in appearance, and has thermodynamic stability, wherein the particle size is generally below 100 nm.

Pyraclostrobin nanoemulsion: also called pyraclostrobin nanoemulsion.

Binary combination of propineb and pyraclostrobin

The propineb is a protective bactericide, and has the main functions of preventing fungal diseases, and in order to achieve the best prevention and treatment effect, the propineb is firstly used in advance, and secondly is preferably mixed with other bactericides, particularly systemic bactericides. Therefore, in order to improve the control effect on crop diseases, propineb is often compounded with other bactericides and/or pesticides. In order to improve the disease control effect of propineb, the invention provides a binary compound nano suspension of propineb and various bactericides based on the technology of obtaining the propineb nano suspension. The method and the scheme provided by the invention can lead the propineb compound nano suspension to be widely applied.

Propofol and pyraclostrobin compound

The propineb has strong compounding performance, can be compounded with up to 21 fungicide components to form various compound preparations respectively, and can further enhance the sterilization spectrum and the action range. The registered dosage form at the present stage is mainly traditional wettable powder and water dispersible granules, and the particle size of the particles is above micron level. The registered crops mainly comprise crops such as apples, cucumbers, potatoes, tomatoes, grapes, rice, watermelons and the like, and the main diseases for controlling are diseases of flagelliform mycotina, ascomycotina and semi-known mycotina such as alternaria leaf spot, downy mildew, anthracnose, early blight, late blight and the like.

Pyraclostrobin is methoxy acrylic bactericide, and has effects of protecting, treating and blade penetrating and conducting by inhibiting mitochondrial respiration to cause cell death. The pesticide is mainly used for preventing and treating various diseases caused by fungi on crops, and has good prevention effect on wheat powdery mildew and scab. Besides direct action on pathogenic bacteria, pyraclostrobin can also mutagenize physiological phenomena of a plurality of crops, especially grains, such as improving nitrogen absorption, thereby promoting rapid growth of crops and improving crop yield, and achieving the purpose of high yield of crops.

The two are compounded, and the composition has the functions of protecting, treating and enhancing the penetration and conduction of leaves, has long lasting period, is used in early onset of disease, can effectively prevent pathogen invasion, improve plant immunity and reduce the onset frequency and the administration frequency. Is effective on most fungal diseases, including downy mildew, alternaria leaf spot, early blight, anthracnose, powdery mildew, cladosporium cucumerinum, rust disease, leaf spot and the like.

Propofol and pyraclostrobin binary compound preparation

According to the existing condition of the binary compound registration certificate of propineb/pyraclostrobin, the control targets, the dosage and the consideration are as follows:

(1) Control target: downy mildew of grape

50% (40% + 10%), grape downy mildew, 2000-3000 times, active ingredient dosage: 6.7 to 10 g of propineb and 1.7 to 2.5 g of pyraclostrobin

50% (45% +5%), grape downy mildew, 800-1600 times, and the dosage of the active ingredients is as follows: 14 to 28 g of propineb and 1.6 to 3.2 g of pyraclostrobin

The patent of the invention is as follows: the dosage of the propineb/pyraclostrobin is 6-30/1.5-3.5 g according to the water consumption of 50 kg.

(2) Control target: downy mildew of cucumber

34 percent (30% +4%), cucumber downy mildew, 225-250 g/mu, and the dosage of the active ingredients is as follows: 67.5 to 75 g of propineb and 9 to 10 g of pyraclostrobin

67% (59.6% + 7.4%), cucumber downy mildew, 110-140 g/mu, active ingredient dosage: 65.6 to 83.4 g of propineb and 8.1 to 10.4 g of pyraclostrobin

The patent of the invention is as follows: the dosage of the propineb and the pyraclostrobin is 60-85/8-10 g.

(3) And (3) target: leaf spot of cucumber

70 percent (65% +5%), 50-60 g/mu of cucumber target spot disease, and the dosage of the active ingredients is as follows: 32.5-39 g propineb and 2.5-3 g pyraclostrobin for reference dosage

(4) And (3) target: leaf spot of apple

75 percent (65 percent+10 percent), 2500 to 3000 times of apple alternaria leaf spot and the dosage of the effective components: 43-52 g of propineb and 6.7-8 g of pyraclostrobin

50% (45% +5%) of apple alternaria leaf spot, 800-1200 times of the dosage of effective components: 75-112 g of propineb and 8.3-12.5 g of pyraclostrobin

The patent of the invention is as follows: 200 kg of water consumption per mu and 43-112/6-12 g of propineb/pyraclostrobin.

(5) And (3) target: late blight of potato

59% (53.1% +5.9%), 45-50 g/mu, and the dosage of the active ingredients: 23.9-26.6 g of propineb and 2.65-2.95 g of pyraclostrobin, wherein the binary compound nano suspension for reference dosage of the propineb and pyraclostrobin refers to nano suspension below 100 nanometers; the binary compound nano suspension of the propineb and pyraclostrobin below 100 nanometers is formed by diluting and mixing at least two components with water:

Binary compound nano suspension of propineb and pyraclostrobin

Previous applications (PCT/CN 2022/139833) have described nanosuspensions of mancozeb in combination with metalaxyl. On the basis, the invention adopts propineb to add pyraclostrobin to form the nano suspension of the binary pesticide. The pyraclostrobin is added into the component A in the form of nano emulsion respectively, and when two components are mixed according to certain conditions, the particle existence form of the pyraclostrobin depends on the dilution water amount and the amount of high polymer auxiliary agent in the system. When the water amount is small, the amount of the diluted polymer auxiliary agent can continuously maintain the existence of the nano micelle, and at the moment, the propineb nano crystal grain and the pyraclostrobin nano colloidal particle coexist. If the water addition amount is not enough to maintain the concentration of the minimum high molecular auxiliary agent required by the nano colloidal particles, the micelle can disappear, and pyraclostrobin can be separated out in the water in the form of nano crystal grains to become a nano crystal grain mixture of two pesticide active ingredients or a nano crystal grain mixture formed by mixing the two pesticide active ingredients, and coexist in the nano suspension.

The two components are as follows:

component A: a water-soluble propineb salt or a water-soluble propineb salt aqueous solution, a water-soluble polymer auxiliary agent; the water-soluble propineb salt is one of propineb, propineb sodium and propineb potassium or a mixture of at least two of the water-soluble propineb salt and the propineb potassium; the water-soluble polymer auxiliary agent is a composite auxiliary agent formed by at least one nonionic surfactant or an aqueous solution thereof;

Meanwhile, adding pyraclostrobin nanoemulsion into the component A;

component B: is prepared from zinc salt or aqueous solution of zinc salt according to a certain mass ratio; zinc salt is at least one kind of salt composition;

the component B can be a solid mixture of zinc salt, can be an aqueous solution formed by adding water, and can be further added with a water-soluble polymer auxiliary agent.

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

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

The dosage of the water-soluble polymer auxiliary agent comprises the sum of the dosage of the polymer auxiliary agents in the component A and the component B, and the ratio of the dosage of the polymer auxiliary agent to the water consumption for dilution is not more than 1:1500. Preferably, not greater than 1:1200; more preferably not greater than 1:1000.

The dilution water contains all of the water in the system.

Nonionic surfactant selected from water-soluble starch and its derivatives, water-soluble guar gum and its derivatives, polyoxypropylene-polyoxyethylene block copolymer, alkylaryl polyoxypropylene polyoxyethylene ether, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, fatty amine polyoxyethylene ether, castor oil polyoxyethylene ether, tween, alkyl polyglycoside, polyvinyl alcohol, etc. Preferably, the polyoxypropylene-polyoxyethylene block copolymer, alkylaryl polyoxypropylene polyoxyethylene ether, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, castor oil polyoxyethylene ether, tween, alkyl polyglycoside, and the like.

Further, the propineb nano-suspension of less than 100 nm has an hour-level stabilization period.

When the propineb salt and the zinc salt are propineb and zinc sulfate respectively, the propineb has two acid groups, and the zinc ion is considered as divalent metal ion, and has tetravalent coordination activity, and the molecular (molar) ratio is in the range of:

propineb/zinc sulfate=1:0.50-1.01

Preferably, propineb/zinc sulfate=1:0.90-1.00

In industrial production, the adopted molar ratio of the propineb to the zinc sulfate is=1:1.01. The zinc sulfate was used in a slight excess to complete the propineb reaction. It is recognized that zinc ions have multiple valence properties that result in the product propineb being insoluble in water and solvents, which act like cross-linking agents. The invention completes the reaction of propineb and zinc sulfate in the process of diluting with water. The excessive zinc ions are not favorable for dispersing and stabilizing the generated propineb nano ions, so that the zinc sulfate is adopted in the invention, and the molar ratio is close to or equal to 1.

In order to reduce the packaging and transportation cost of the preparation, the specifications of each component of the preparation can be the same or different. In the specification of taking zinc salt aqueous solution as the component B, a certain amount of water-soluble polymer auxiliary agent can be added, and the mass concentration of the water-soluble polymer auxiliary agent is preferably not higher than 10% when the component B does not generate a turbid state.

Propineb nano suspension below 100nm

In order to improve the drug effect of nano propineb, the particle size of the nano propineb needs to be reduced as much as possible. The original purpose of researching nano pesticide is to improve the pesticide effect and reduce the pesticide dosage. The particle size of conventional pesticide formulations is typically on the order of microns, decreasing it to the corresponding nanometer size, spanning three orders of magnitude, and increasing the number of particles varies when decreasing to different orders of magnitude. For example, the conventional preparation generally had particle sizes reduced from 2 μm to 200nm, 20nm and 2nm, respectively, and theoretically, the particle numbers were increased by 1000 (10 ³ ) 100 ten thousand (10) ⁶ ) 10 billion (10) ⁹ ) Multiple times. From this, it is found that the effect of the drug effect is different due to the difference in the decrease in the particle size and the increase in the number of particles. Therefore, in view of improving the efficacy of the nano-pesticide, the size of the particles should be reduced as much as possible.

In order to further improve the drug effect of nano propineb, the particle size of the nano propineb is desirably reduced to 100nm or less. This is based on two aspects. First, the dimensions below 100nm are the lowest dimensions that define the nanomaterial must have in any dimension. Secondly, the pesticide particles are 1-100 nm, the preparation belongs to a colloidal solution, the appearance is clear and transparent, and a beam of illumination solution can see a light column with clear boundary, so that the pesticide composition accords with the description of the 'Tyndall' phenomenon.

Concentration of suspension

The suspension with small concentration has a smaller number of particles below 100nm and has little influence on transparency. This is the case for systems with a propineb dosage of 1500 g/ha, diluted with more than 50 kg of water.

In the suspension having a large concentration, the amount of particles less than 100nm is smaller, and the influence on transparency is relatively large. For a system with the dosage of propineb of 1500 g/hectare, the transparency of the suspension can be temporarily appeared by diluting with 20 kg of water, but the concentration is too high, particles are easy to collide with each other, the crystallization grows up and aggregates, and the transparency stability of the suspension is obviously affected.

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

Stabilization period

The binary compound nano suspension of propineb and pyraclostrobin prepared by the invention is a solution with transparent appearance and apparent water solubility, but is not a solution with thermodynamic stability. Therefore, the time for which the nano propineb suspension is kept in an apparent transparent state is not infinitely long, but there is a stationary phase. In view of the operation characteristics of spraying operation, the required operation time is at least more than 1 hour after the nano propineb suspension is prepared, so that the length of the stabilization period can be described in hours. Thus, the invention proposes the concept that a nano-sized propineb suspension below 100nm has a "stationary phase". Namely, the propineb suspension below 100nm prepared by the method can finish spraying operation in the period that the solution keeps transparent, and the stable period is at least 1 hour.

From an application point of view, the stationary phase can be further divided into 4 time periods: within 1 hour, 1 to 5 hours, 5 to 10 hours and more than 10 hours.

During the stationary phase, the nanoscale suspension remains transparent, i.e. it is ensured that the particle size is still less than 100nm.

Hour-level stationary phase

From the point of view of the spraying operation, analysis:

the stabilizing time is about 1 hour, and the operation time for spraying operation is not enough; multiple-formulated nanosuspensions with stability periods exceeding 5 hours are difficult to achieve.

The stabilizing time is between 2 and 5 hours, and the spraying operation of most pesticide appliances can be completed in the time.

The hour-level stabilization period refers to a stabilization time of 1-5 hours.

For the hour-level stabilization period, a refinement stage may also be performed.

1-2 hours is the basic period of the spraying operation; in most cases the spraying device is capable of performing the task.

2-5 hours is the full period of the spraying operation; can be suitable for delayed spraying operation in special situations.

Component and auxiliary agent of nano suspension of propineb and pyraclostrobin

The traditional propineb single-dose preparation and the binary compound preparation are usually only one component, and can be sprayed after being diluted by water, but most of pesticide particles have the size of more than microns. The invention adopts at least two component modes to obtain nano propineb suspension, and the nano propineb suspension below 100 nanometers can be obtained by diluting with water according to a certain method

Two component scheme

The nano suspension compounded by the propineb and pyraclostrobin below 100 nanometers has an hour-level stability period and is a system formed by mixing and reacting two components. They are respectively:

component A: the transparent aqueous solution is formed by combining propineb, sodium propineb or potassium propineb solid or aqueous solution thereof, pyraclostrobin nanoemulsion and water. Wherein, the precursor of propineb is generated, and the water-soluble polymer surfactant and water which have the functions of dispersion, suspension and stabilization are the basic components of the component A. On the basis, the nano emulsion of the active ingredients can be added.

In the component A, the pyraclostrobin nanoemulsion contains a certain amount of water-soluble polymer auxiliary agent. If necessary, a water-soluble polymer auxiliary agent may be further added.

Component B is a system of zinc salt mixtures in certain proportions, and the system has three forms: solid inorganic zinc salt (component B) ₁ ) Aqueous solutions of inorganic zinc salts (component B) ₂ ) Aqueous solution (component) composed of inorganic zinc salt and water-soluble polymer auxiliary agentB ₃ )。

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

Due to the limited solubility of inorganic zinc salts in water, it is desirable to limit the amount of water used in order to minimize the capacity of component B. In addition, the solubility of the inorganic salt is also influenced by the dosage of the auxiliary agent, so that the addition amount of the water-soluble polymer auxiliary agent in the component B is limited.

B ₃ The improvement consists in distributing the water-soluble polymer auxiliary agent into the component A and the component B. In view of the several limitations of component B, there is an upper limit on the proportion of water-soluble polymeric adjuvants in component B, unless the limitation of component B on certain capacity is not taken into account.

Component proportion for producing propineb

The two-component improvement comprises two components:

component A: an aqueous solution of propineb (or sodium, potassium) or propineb (sodium, potassium) is used, followed by the addition of an auxiliary agent.

Component B: zinc sulfate (or zinc acetate, zinc chloride, zinc nitrate) is dissolved in water according to a certain proportion; auxiliaries may be added.

In the component A and the component B, the amount of the active ingredient is the basis for determining the constitution of the two components. Propineb (or sodium propineb and potassium propineb) in the component A is a precursor for generating nano propineb and is a basis for determining the composition of the component B.

The invention is exemplified by a 1/15 hectare field if 100 g propineb spray is required. The two-component design was performed based on 100 g of a 100nm lower propineb suspension.

Component a requires propineb or sodium, potassium, preferably propineb as precursor, about 90 grams. According to the foregoing rule of distribution of adjuvants in component A and component B, the vast majority of the adjuvants will be distributed in component A. If both component A and component B are in a 500 g mass pack specification, the amount of water is that amount after removal of propineb and adjuvant.

Component B, the amount of inorganic zinc salt required for reaction with propineb is first determined, zinc sulphate being preferred in the present invention. It is generally believed that zinc ions react with propineb to form salts in place of ammonium ions, resulting in a linear repeating structure or complex structure, and zinc ions also have tetravalent coordination ability, possibly forming complex structures.

The prior literature shows that in the synthesis process of propineb, the molecular (molar) ratio between propineb and zinc ions is 1:1.00-1.05. Propineb has two ammonium acid groups, zinc ion is 2 valence metal ion, the molar ratio of the molecules should be 1:1, and a small excess is used for ensuring the reaction is complete. Although zinc ions also have 4-valent coordination properties, elemental analysis of the propineb sample found that the zinc element content was near 22.8% of theory, indicating that propineb (propylenebisdithiocarbamate) was 1:1 bound to zinc sulfate.

In the case of using the precursor propineb with a mass of 90 g (0.346 mol, 100 g propineb is produced), zinc salt is used as zinc sulfate (anhydrous compound), and the mass of the same mol is 56.5 g, but a mass slightly lower than this can be used.

Component proportion of nano suspension for generating propineb and pyraclostrobin compound

The two-component scheme comprises two active ingredients: propineb and pyraclostrobin

Component A: the pyraclostrobin nanoemulsion is added with a solid of propineb, sodium propineb or potassium propineb or an aqueous solution thereof or an aqueous solution of at least two mixtures thereof, and then the addition of the auxiliary agent can be continued.

Component B: zinc sulfate (or zinc acetate, zinc chloride, zinc nitrate) is dissolved in water according to a certain proportion; adjuvants may also be added.

In the component A and the component B, the amount of the active ingredient is the basis for determining the constitution of the two components. Propineb, propineb sodium or propineb potassium in the component A is a precursor for generating nano propineb and is a basis for determining the composition of the component B.

Dispensing of auxiliary agent of component A and component B

The auxiliary is mainly in the component A.

The component A mainly contains propineb (or propineb, potassium propineb) and pyraclostrobin nanoemulsion.

The reason that the component A and the component B must be dispensed is that the two react when mixed together. If a two-component method is adopted, the pyraclostrobin nanoemulsion in the component A contains an auxiliary agent, and the auxiliary agent is added unless a third component of a single auxiliary agent is added. This complicates the components and dilution process. The condition of adding the auxiliary agent in the component A is as follows: the propineb and the auxiliary agent are both dissolved in water and can be mixed, and unstable phenomena such as precipitation and the like can not occur. However, due to the high content of propineb and auxiliary agent and high viscosity, the operation is not easy, a certain amount of water is added to dissolve and dilute the propineb and auxiliary agent, the viscosity is reduced, and the operation is convenient. The amount of water added, after achieving the above-mentioned objects, should minimize the total mass of component a, reducing the costs of production, packaging and transportation.

The component B is mainly zinc salt solid, or aqueous solution thereof, or aqueous solution of polymer auxiliary agent thereof.

Component B may be a solid mixture of zinc salts. It is necessary to dissolve in water before mixing with component A, and for convenience, their aqueous solutions may be used. They have limited solubility and require a higher amount of water to dissolve. Optionally, an auxiliary agent is added or not according to the dissolution condition. The reasons are two: firstly, a large amount of auxiliary agent is added into the component B, and a coagulation film forming phenomenon can occur on the surface of a mixed solution of zinc salt, the auxiliary agent and water, so that the next operation is influenced; secondly, if the amount of the auxiliary agent in the component A can suspend and disperse the generated nano crystal grains of propineb and pyraclostrobin, the auxiliary agent can be not added in the component B. However, in view of pest control for orchards, the amount of water sprayed is large, usually as much as 200 to 300 kg/mu. If the amount of auxiliary agent in component A is not sufficient to support the dispersion and suspension of the nanocrystalline particles, an appropriate auxiliary agent should be added to component B. The premise is that the amount of the auxiliary agent is added into the zinc salt aqueous solution, so that the component B still keeps transparent, and the condition that the surface of the mixed solution is coagulated into a film does not occur. The mass concentration of the auxiliary added to component B is generally not higher than 10%.

Although both component a and component B can solve the above-mentioned difficulties by expanding the capacity, the increase in the specifications of the amounts of both components undoubtedly increases the production, packaging and transportation costs. By comprehensively considering the factors, on the premise of generating the nano particles of the propineb compound pesticide with unit mass, the relationship between the consumption of each component and the specification of the product is balanced, and the auxiliary agent and the water are used as little as possible, which is an important factor to consider.

Water-soluble polymer auxiliary agent

The invention relates to a water-soluble polymer auxiliary agent with dispersing and suspending functions, which relates to the size of nano crystal grain sizes of propineb and pyraclostrobin generated during dilution and mixing of two or three components, and important component substances capable of stably dispersing and suspending.

The water-soluble polymer auxiliary agent belongs to a polymer surfactant, has the properties of dispersing, suspending, improving viscosity and the like, and is derived from a hydrophobic chain structure and a hydrophilic functional group. These groups distributed on the terminal and pendant groups are hydroxyl, carboxyl, carboxymethyl, sulfonic, sulfuric, phosphoric, amino, quaternary ammonium groups, etc. According to the nature of the hydrophilic group, natural and synthetic polymers are classified as anionic, cationic, nonionic and zwitterionic polymers.

The principle of selecting the water-soluble polymer auxiliary agent is that (1) pesticide nano-crystal grains generated by stable dispersion and suspension can be selected; (2) is not affected by the reaction of polyvalent metal ions and water-soluble propineb salt; (3) is as environment-friendly as possible. Therefore, the invention selects the nonionic polymer auxiliary agent of the natural substance derivative. Such as polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers, various polyoxyethylene ethers having fatty alcohols, fatty acids, fatty amines, aryl phenols, oil groups, etc. as hydrophobic groups, such as peregal (peregal) series, OP series, tween (Tween) series, polyol series, ricinoleic acid series, alkyl polyglycosides, etc. However, nonylphenol polyoxyethylene ethers having a female toxicity should be avoided.

The nano suspension of propineb and pyraclostrobin is produced by the reaction of water-soluble propineb (or sodium) and zinc salt in the process of diluting and mixing by adding water, and emulsion particles or nano crystal grains are produced by the nano emulsion of pyraclostrobin.

The dosage of the polymer auxiliary agent is related to the dosage of the propineb/pyraclostrobin generated by the system and the water consumption for dilution. The concentration of the polymer auxiliary agent is at least 0.1-0.5%.

The detection shows that the particle size of the propineb/pyraclostrobin nano suspension is about 30-80 nm. The nanometer suspension can be in a stable state within 2-5 h, does not precipitate or precipitate, and is directly applied to the spraying operation of various pesticide spraying devices.

And fifthly, the propineb and pyraclostrobin nano suspension is mainly propineb nano particles, and is formed by reaction in the diluting and mixing process. Not only the synthesis and purification process of the propineb technical from propineb or propineb in the pesticide technical factory is omitted, but also the multi-step physical processing process of the propineb and other technical into wettable powder in the pesticide preparation factory is omitted. The solution provided by the invention can be directly applied to plant protection links of agricultural production, the process is obviously energy-saving and environment-friendly, the production cost can be obviously reduced, and the nano suspension dispersion liquid with the propineb particle size smaller than 100nm is obtained. The small-size nano particles can fully exert the drug effect, obviously reduce the pesticide dosage and play a role in reducing and enhancing the efficiency in agricultural production.

The flow chart of the preparation of the propineb and pyraclostrobin nano-suspension by dilution with water is shown in figure 2.

The key technology of the invention is as follows:

1. process for the production of nanosuspensions

The innovation provides a new mode and a new method for preparing the nanometer suspending agent by using pesticide varieties which are insoluble in water and organic solvents and contain polyvalent metal ions. The precursor of the target product is mixed with corresponding metal salt by utilizing the process that the pesticide needs to be diluted by adding water, and the mixing and stirring speed of reactants is controlled by utilizing the principle of rapid reaction of metal ions, so that the directly used nano suspension with the particle size smaller than 100 nanometers is obtained. The method omits the chemical synthesis and purification process of the propineb raw medicine prepared from propineb or sodium and potassium in the pesticide raw medicine factory, and omits the multi-step physical processing process of the pesticide preparation factory for processing the propineb raw medicine into the existing dosage form wettable powder. This innovative research idea, mode of preparation and method are the most important key technologies of the present invention. The key technology is not only suitable for the occasion of compounding propineb and other bactericides, but also suitable for the process of preparing the nano suspending agent similar to the pesticide variety.

2. Concentration of propineb

The concentration of propineb produced in the diluted water is controlled by the component A with propineb or sodium propineb as the main component and the component B with zinc salt as the main component. That is, if the amount of the active ingredient propineb is 100 g/mu, the concentration of propineb produced by the reaction of propineb or sodium propineb with zinc sulfate is affected by the dilution water amount. 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 water consumption should be 100-200 kg. If the water consumption is too small, for example, less than 100 kg, the size of the generated particles is large, and the transparency of the diluent is poor, because the concentration of the particles is high, the probability of forming particles of a larger size by mutual collision is increased, and the stability is lowered, which is disadvantageous in forming particles of a size of 100nm or less. If the water amount exceeds 200 kg, although a transparent diluent can be obtained, the concentration of the dispersant contained in the component is significantly reduced and the stability of the diluted liquid medicine is deteriorated. Therefore, controlling the concentration of the finally produced propineb, namely controlling the water consumption of water dilution, is one of the key technologies for obtaining the propineb nano-suspension.

3. Dilution water consumption

When the dosages of the component A and the component B are fixed, the dilution water consumption is one of key technologies for controlling the dilution concentration of the two components so as to obtain the propineb and pyraclostrobin nano-suspension. The dilution water determines the concentration of component a and component B. If the water consumption is too small, for example, 20 kg, the concentration of the component A and the component B is large, the concentration of the produced nanoparticles is high, and the stabilizing time for forming the particle size of 100nm or less is short. If the water amount exceeds 300 kg, a transparent diluent can be obtained, but the concentration of the auxiliary contained in the component is significantly reduced, and the stability of the nanosuspension is also deteriorated unless the amount of the auxiliary is increased. Thus, when the amounts of component a and component B are fixed, e.g., 500 grams per component, a suitable dilution water usage, e.g., a water usage range of greater than 20 kg and less than 300 kg, is one of the key techniques to control the concentrations of the two components and to produce a stable nanosuspension of propineb and pyraclostrobin.

4. Types and amounts of auxiliary (dispersant)

The selection of the type and amount of dispersant used is a further key technique for obtaining propineb nanosuspension. However, when propineb or sodium propineb and zinc salt form particles of propineb in water, the newly formed particles of propineb cannot be kept substantially unchanged in size by the dispersion of a large amount of water and stirring. This is because the particles dispersed in the water are not stationary, the particles are all in constant motion and collide with each other, and as a result of the effective collision, the particles are combined, the crystals grow up, and finally precipitate. An effective method for preventing the size of the generated particles from becoming larger is to select a proper type of dispersing agent and determine the proper amount of the dispersing agent, so that the nano particles of the effective ingredient are uniformly dispersed in a solution formed by the dispersing agent in water. The dispersant is water soluble polymer and may be dissolved in water. The microscopic state of the water-soluble polymer in water exists in a random coil mode. The size of the random coil is much larger than the newly generated propineb particle size, which can be larger than 1 micron depending on the size and amount of molecular weight. If the propineb nanoparticles generated at this time are smaller than 100nm, for example, several nm, tens of nm, these particles can enter the inside of the random coil. To some extent, random coils can prevent and slow down the collisions between these particles, thus improving the stability of propineb nanoparticles. This is the effect of adding the dispersant.

However, there is a problem in that the water-soluble polymers are of different types and whether or not all the water-soluble polymers can be used. The invention tests the types of various water-soluble polymers, and the result is negative. Among the numerous anionic, cationic and nonionic surfactants, only nonionic polymeric adjuvants currently have the desired effect, such as alkyl alcohols, polyoxyethylene ethers of alkyl acids, polyoxypropylene-polyoxyethylene ethers of alkylaryl groups, alkyl polyglycosides, castor oil polyoxyethylene ethers, tween-80, etc., but only a few have the best effect. The reason why the anionic surfactant cannot be used is that the reaction mechanism of propineb formation in the dilution process with water is essentially the process of substituting ammonium ions or sodium ions by polyvalent metal ions to form salts or forming complexes, and when the anionic surfactant is used as the dispersing agent, the polyvalent metal ions are completely likely to react with the sodium salt of an acid group in the dispersing agent in the same way, so that the dispersing agent precipitates out together with propineb nano particles which are entrapped and formed in the water-soluble state, and the dispersing effect is not achieved. The invention does not exclude the special case that the optimal combination of the individual cationic surfactants with the appropriate anionic or nonionic surfactants is achieved without precipitation occurring when dissolved in water.

The important role of the water-soluble polymer auxiliary agent is self-evident. The invention mixes the propineb or sodium propineb or potassium propineb dissolved in water with zinc salt such as zinc sulfate to generate zinc propineb suspension below 100 nm. In the system, if the system does not contain a surfactant, especially does not contain a water-soluble high-molecular surfactant, the generated nano grains can collide with each other continuously, so that crystals grow up and aggregate until macroscopic precipitation occurs. When water-soluble high molecular surfactant with proper types and dosage exists in the system, the generated nano crystal grains can enter into random coils formed by the water-soluble high molecular auxiliary agent, so that the collision and crystal growth among the nano crystal grains can be prevented and delayed, and the generated propineb nano crystal grains can be dispersed, suspended and stabilized.

The type and the amount of the water-soluble polymer auxiliary agent used in the invention can be determined by experiments. The kind of the water-soluble polymer auxiliary agent can be determined by the stability test of different auxiliary agents under fixed conditions and observing the effect. The category test of the auxiliary agent comprises a single agent or two or more compound auxiliary agents of the water-soluble polymer auxiliary agent. In the present invention, the types of various water-soluble polymer auxiliaries will be exemplified in the test examples. The determination of the amount of the water-soluble polymer auxiliary agent is based on the following two conditions: firstly, the produced propineb nano suspension liquid is required to be transparent in appearance, so that apparent water solubility is realized, and the particle size can be ensured to be below 100 nm; secondly, the stabilization time of the transparent nanosuspension is between 1 and 10 hours, at least between 1 and 5 hours.

For the system formed by the mixing reaction of the two components, the auxiliary amounts are distributed into component A and component B. Theoretically, if the two components are not limited in capacity, the proportion of the auxiliary agent in the component A and the component B can be arbitrarily allocated; if there is a limit to the packaging capacity of the two components, for example, for application to a field of 1/15 hectare (100 g propineb is produced), the amount of adjuvant added to component B is greatly limited given that the amount of water used to dissolve the zinc salt in component B is greater and that the solubility of this inorganic salt solution to the adjuvant is poor, given that component A and component B are each 500 g. Thus, the amount of the two-component adjuvant dispensed can be determined by the formula:

amount of auxiliary agent _{(component A)} Total amount of auxiliaries-amount of auxiliaries _{(component B)}

The amount of auxiliary added to component B in the case of a fixed capacity can be determined by the fact that the addition of auxiliary occurs after component B, the upper limit of the amount of auxiliary added to component B being the upper limit when the system changes from transparent to turbid.

The auxiliary agent dosage of the invention is relative to the water consumption of the diluted water. The dilution water consumption is large, and the addition agent consumption is properly increased. The ratio of the amount of auxiliary agent to the amount of dilution water is at least within 1:1200, preferably within 1:1000.

5. Addition mode and stirring mode

The feeding mode is also one of important factors influencing the performance of the propineb and pyraclostrobin nano suspension. How does the dilution water usage and the ratio of the components a and B distributed after they are determined, during mixing? The size and stability of the resulting particles are affected. For example, the manner of joining may involve the following problems:

whether diluent X of component a is added to diluent Y of component B or diluent Y of component B is added to diluent X of component a?

How does it add? Is pouring into the container for addition, adding in thin stream, or dripping? Is spray addition? Is single point addition, or multiple point addition? Is continuous or intermittent? Etc.

In practice, after the addition mode is determined, stirring mode problems are also involved. Likewise, there are different ways to stir, be it manual stirring, or mechanical stirring? Is single point stirring, or multi point stirring? Is continuous stirring or intermittent stirring? Etc. The stirring mode is closely related to the stirring speed.

The method of feeding, the stirring method and the stirring speed are all related to the concentration of the reactant in the reaction area formed by mixing the two-component diluent instantly and the problem of rapid dispersion of the product. The most direct method for judging the two modes and the standard of stirring speed is to observe whether the product in the system is in a transparent state or not. If the resulting nanosuspension is clear and transparent and has a long settling time, it is indicated that the addition mode is appropriate and that the stirring mode and stirring speed are effective.

Preparation method of propineb and pyraclostrobin nano suspension

For the two-component scheme, the invention adopts the following technical scheme:

adding the component A diluent to the component B diluent or adding the component B diluent to the component A diluent under the condition that the stirring speed is not less than the effective stirring speed; to produce nano suspension of propineb and pyraclostrobin.

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

component A: consists of water-soluble propineb salt or water-soluble propineb salt water solution and water-soluble polymer auxiliary agent; the water-soluble propineb salt is one of propineb, propineb sodium and propineb potassium or a mixture of at least two of the water-soluble propineb salt and the propineb potassium;

meanwhile, the component A is added with pyraclostrobin nanoemulsion;

component B: is composed of zinc salt solid or its aqueous solution according to a certain proportion.

The adding mode, the adding speed and the stirring speed are controlled, so that nano grains of 100-nanometer propineb and pyraclostrobin are generated in the suspension, and the final suspension is the nano suspension of 100-nanometer propineb and pyraclostrobin.

Stirring mode

And (3) manually stirring: this comparison is consistent with 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 provide a large container with a stirring device. If such conditions are met, the rotational speed of the large stirring device is typically no more than 100 revolutions per minute. Stirring at a rotational speed close to this is sufficient.

For the manual stirring mode, the stirring speed is required to be in accordance with the operation speed of the physiological function of the human body. In order to obtain a stable target product, the material adding speed can be properly reduced, and the material adding speed is determined by observing that the product presents a transparent state in the system.

Mode and rate of addition

In order to make the added materials more uniform and fine, the materials are rapidly dispersed after entering the system, and one component can be added into the other component in a continuous mode, or can be added in intermittent components or dropwise. For the dripping mode, a manual sprayer commonly used in rural areas can be used for spraying and adding, and the adding mode has the best effect. The adding speed is still determined by observing the transparent state of the product in the system.

For the existing pesticide preparation, water is used as a dispersion medium for spraying, the pesticide preparation is usually required to be diluted by adding water before spraying, or the commonly used pesticide preparations are required to be mixed together, and the process is commonly called "barrel mixing". The invention utilizes the process of 'barrel mixing', and the component A and the component B are mixed according to a certain concentration, a certain adding mode and a certain adding speed under the action of a specific auxiliary agent-dispersing agent, thereby directly obtaining the 'barrel mixing' transparent propineb/pyraclostrobin nano suspension capable of being sprayed on site.

Dilution water consumption

Current experimental data shows that: the starting range is reasonable up and down to 30 kg. This dilution water usage has a strong correlation with our target stationary phase. This is a problem of multiple variables, and the content of adjuvants in the composition, the composition of adjuvants, are also influencing factors.

The invention aims to obtain the propineb and pyraclostrobin nano-suspension with the transparent stability period of less than 100 nanometers for 2-5 hours. When the mass of the precursor per unit mass (for example, 90 g propineb) and the metal salt (zinc sulfate) reacted therewith are fixed, and the mass of pyraclostrobin is also fixed, factors that can affect the nanosize and stability properties of the microparticles also include: dilution water consumption, auxiliary agent consumption and preparation method.

The dilution water consumption can influence the size of the grain size and the stability period of the produced nano propineb. The reason is that the water is used as a dispersion medium, which affects the concentration of the propineb solution and the zinc sulfate solution at the moment of contact reaction and the uniformity of dispersion, and thus affects the size of the generated crystal grains, the dispersion effect of the crystal grains and the opportunity of aggregation and growth of crystals. The amount of auxiliary agent used affects the concentration of the aqueous solution in different water consumption, the size of the dispersion, suspension and stabilization effect and the length of the stabilization time of the generated nano crystal grains. The water consumption is too small, so that a limit is generated, for example, when the water consumption for dilution is 20 kg or less, the stable time for generating the transparent propineb and pyraclostrobin nanometer suspension is about 1 hour, and the spraying operation time cannot be fully ensured. Therefore, the dilution water amount needs to be increased.

The invention can produce 100 g of target product, namely propineb and pyraclostrobin suspension liquid with transparent stability period below 100nm for 2-5 hours, and the selected dilution water consumption is 30-300 kg, preferably 50-200 kg.

Three-component basic scheme

The basic scheme of the nano suspension of the propineb and pyraclostrobin below 100 nanometers is a system formed by three components. They are respectively:

component A': consists of propineb, sodium propineb or potassium propineb solid or its aqueous solution, which is a precursor for generating propineb nano-crystalline grains.

Component A' may be propineb or sodium, potassium, or a mixture thereof. The single component or the mixture of the two or the three components can be solid, so that the packaging is simple and convenient, the volume is small, the water-soluble compound can be dissolved in water before use and can be dissolved rapidly, but the water-soluble compound can also be used as an aqueous solution, and the water-soluble compound can be directly diluted to a certain volume before use. The component A' can be added with or without adding water-soluble polymer auxiliary agent with certain mass.

Component B': is composed of zinc salt solid or aqueous solution thereof in a certain proportion, which is polyvalent metal ion required for generating propineb nano-crystalline grains.

Component B' is a mixture of inorganic zinc salts according to a certain proportion. The zinc salt is at least one selected from zinc sulfate, zinc acetate, zinc chloride and zinc nitrate. The component B' may be a solid, so that the package is small in volume, or an aqueous solution thereof may be used. Because of the limitation of the solubility, the formed solution has larger capacity, and is not beneficial to storage and transportation, but is convenient to use. The component B' can be added with or without adding water-soluble polymer auxiliary agent with certain mass.

Component C: pyraclostrobin

The pyraclostrobin nanoemulsion is used as a component C. The pyraclostrobin nanoemulsion contains a certain mass of water-soluble polymer auxiliary agent. If desired, water-soluble polymeric auxiliaries may also be added or not to component C.

The total mass of the water-soluble polymer auxiliary agent required by the three-component scheme is distributed in the component A ', the component B' and the component C and also contained in the pyraclostrobin nanoemulsion in the component C.

[ brief description of the drawings ]

FIG. 1 is a flow chart of a process for preparing a mancozeb original drug and processing the mancozeb original drug into a wettable powder preparation in the prior art;

FIG. 2A schematic flow chart (two components) for preparing propineb and pyraclostrobin nanosuspension

FIG. 3 schematic flow chart (three components) for preparing propineb and pyraclostrobin nanosuspension

[ embodiment ]

The invention relates to a method for preparing a transparent propineb and pyraclostrobin nanometer suspension with the size of below 100nm, which comprises the following steps of:

in the first step, the component A and the component B are diluted respectively according to different water consumption and different dilution ratios to form a component A diluent and a component B diluent.

Secondly, under the condition of mechanical stirring (preferred) or manual stirring, the stirring speed is not less than the effective stirring speed, and the component A diluent is uniformly added into the component B diluent according to a certain adding mode (continuous or intermittent pouring, dripping, spraying and the like); or in the reverse order.

The three-component scheme comprises the following operation steps:

in the first step, the component A 'and the component B' are diluted respectively according to different water consumption and different dilution ratios to form a component A 'diluent and a component B' diluent.

And secondly, adding the component C into the component A' diluent, and stirring and dispersing uniformly.

Thirdly, under the condition of mechanical stirring (preferred) or manual stirring, the stirring speed is not less than the effective stirring speed, and the component A 'and the component C diluent are uniformly added into the component B' diluent according to a certain adding mode (continuous or intermittent pouring, dripping, spraying and the like); or in the reverse order.

The following are examples:

example 1

The propineb/pyraclostrobin nano suspension can be used for preventing and treating alternaria leaf spot of apple trees, the dosage of the active ingredients is 80/8 g/mu respectively, and the dilution water consumption of spraying apple trees is 200 kg/mu. The propineb required to produce 80 grams of propineb was 72 grams.

The components are as follows: the proportions of the components, the amount of dilution water, the amount of water distribution, the sequence and mode of addition and the test results are shown in the following table:

the operation method comprises the following steps:

the component A and the component B are diluted and dissolved according to the ratio of 4/5 and 1/5 of the water consumption of 200 kg respectively, so as to obtain a component A diluent and a component B diluent respectively. And (3) adding the component B diluent into the component A diluent in a continuous trickle mode under manual stirring to obtain the propineb/pyraclostrobin nano suspension with transparent appearance. The stabilization time was 4 hours.

Example 2

This example is essentially the same as example 1, but a three-component scheme was implemented. The composition, method of operation and manner of addition of the components are varied.

The components are as follows: the proportions of the components, the amount of dilution water, the amount of water distribution, the sequence and mode of addition and the test results are shown in the following table:

the operation method comprises the following steps:

the component A 'and the component B' are diluted and dissolved according to the ratio of 4/5 and 1/5 of 200 kg water consumption, so as to obtain a component A 'diluent and a component B' diluent respectively. And adding the component C into the component A 'diluent, and uniformly stirring to form a mixed diluent of the component A' diluent and the component C. And (3) adding the component B 'diluent into the mixed diluent of the component A' diluent and the component C in a continuous spraying manner under manual stirring to obtain the propineb/pyraclostrobin nano suspension with transparent appearance. The stabilization time was 4 hours.

Example 3

The propineb/pyraclostrobin nano suspension can be used for preventing and treating grape downy mildew, the dosage of the active ingredients is 30/3 g/mu respectively, and the dilution water consumption of sprayed grapes is 50 kg/mu. The propineb required to produce 30 grams of propineb was 27 grams.

The components are as follows: the proportions of the components, the amount of dilution water, the amount of water distribution, the sequence and mode of addition and the test results are shown in the following table:

the operation method comprises the following steps:

the component A and the component B are diluted and dissolved according to the proportion of 2/3 and 1/3 of the water consumption of 50 kg respectively, so as to obtain a component A diluent and a component B diluent respectively. And adding the component B diluent into the component A diluent in a continuous spraying mode under manual stirring to obtain the propineb/pyraclostrobin nano suspension with transparent appearance. The stabilization time was 4.5 hours.

Example 4

The propineb/pyraclostrobin nano suspension can be used for preventing and treating downy mildew of cucumbers, the dosage of the active ingredients is 60/8 g/mu respectively, and the dilution water consumption of the sprayed cucumbers is 40 kg/mu. The propineb required to produce 60 grams of propineb was 54 grams.

The components are as follows: the proportions of the components, the amount of dilution water, the amount of water distribution, the sequence and mode of addition and the test results are shown in the following table:

The operation method comprises the following steps:

the component A and the component B are diluted and dissolved according to the ratio of 4/5 and 1/5 of the water consumption of 40 kg respectively, so as to obtain a component A diluent and a component B diluent respectively. And (3) under the condition of manual stirring, continuously dropwise adding the component B diluent into the component A diluent to obtain the propineb/pyraclostrobin nano suspension with transparent appearance. The stabilization time was 5 hours.

Example 5

The propineb/pyraclostrobin nano suspension can be used for preventing and treating potato late blight, the dosage of the active ingredients is 25/2.5 g/mu respectively, and the dilution water consumption of the sprayed potato is 20 kg/mu. The propineb required to produce 25 grams of propineb was about 23 grams.

The components are as follows: the proportions of the components, the amount of dilution water, the amount of water distribution, the sequence and mode of addition and the test results are shown in the following table:

the operation method comprises the following steps:

the component A 'and the component B' are diluted and dissolved according to the proportion of 1/3 and 2/3 of the water consumption of 20 kg respectively, and the component A 'diluent and the component B' diluent are obtained respectively. And adding the component C into the component B 'diluent to form a mixed diluent of the component B' diluent and the component C. And (3) adding the component A 'diluent into the mixed diluent of the component B' diluent and the component C in a continuous spraying manner under manual stirring to obtain the propineb/pyraclostrobin nano suspension with transparent appearance. The stabilization time was 2 hours.

Claims (10)

1. A broad-spectrum nanometer suspension containing pyraclostrobin for preventing and treating fungal diseases; the broad spectrum nano suspension refers to nano suspension below 100 nanometers; the nano suspension below 100 nanometers is formed by diluting and mixing two components with water:

component A: a water-soluble propineb salt or a water-soluble propineb salt aqueous solution, a water-soluble polymer auxiliary agent; the water-soluble propineb salt is one of propineb, propineb sodium and propineb potassium, or a mixture of at least two of the water-soluble propineb salt and the propineb potassium

Meanwhile, adding pyraclostrobin nanoemulsion into the component A;

component B: is prepared from zinc salt or aqueous solution of zinc salt according to a certain mass ratio; zinc salts are constituent substances of at least one salt.

2. The broad spectrum nanosuspension of claim 1, wherein the nanosuspension of less than 100 nanometers has an hour-scale stability period.

3. The broad spectrum nanosuspension according to claim 1, wherein component B, is added with a water soluble polymeric auxiliary agent and water to form an aqueous solution.

4. The broad spectrum nanosuspension according to claim 1, wherein the water soluble polymeric adjunct is a nonionic surfactant.

5. The broad spectrum nanosuspension according to claim 1, wherein the ratio of the amount of water soluble polymeric auxiliary agent to the amount of dilution water is not greater than 1:1200.

6. The broad spectrum nanosuspension according to claim 4, wherein 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 copolymer, alkylaryl polyoxypropylene polyoxyethylene ether, OP-10, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, fatty amine polyoxyethylene ether, castor oil polyoxyethylene ether, tween, alkyl polyglycoside, and polyvinyl alcohol.

7. Broad spectrum nanosuspension according to one of claims 1 to 6, wherein the zinc salt is selected from at least one of zinc sulphate, zinc acetate, zinc chloride, zinc nitrate.

8. The broad spectrum nanosuspension according to claim 7, wherein when the propineb salt and the zinc salt are propineb ammonium and zinc sulphate, respectively, the molar ratio ranges from:

propineb/zinc sulfate=1:0.50-1.01

Preferably, propineb to zinc sulphate=1:0.90-1.00.

9. A process for the preparation of a broad-spectrum nanosuspension containing pyraclostrobin as claimed in claims 1 to 8 for controlling fungal diseases;

adding the component A diluent into the component B diluent under the condition that the stirring speed is not less than the effective stirring speed; or alternatively

Adding the component B diluent into the component A diluent to form binary compound nano suspension;

the component A diluent and the component B diluent are respectively aqueous solutions formed by diluting the component A and the component B with water.

10. The method of claim 9, wherein one component is added to the other component in one of four ways: continuously adding, intermittently adding, dripping, and spraying.