Production process of water-soluble thiophanate-methyl preparation

Abstract

The invention discloses a production process of a water-soluble thiophanate-methyl preparation, and belongs to the technical field of pesticide preparations, the production process comprises the following steps: preparing porous drug-loaded microspheres by a spray drying method, crosslinking chitosan and methoxypolyethylene glycol under the action of a crosslinking agent to form polyethylene glycol modified chitosan, and coating thiophanate-methyl by using the polyethylene glycol modified chitosan as a loading material to prepare the water-soluble thiophanate-methyl preparation. Under the synergistic effect of the pore-forming agent, the granulation and pore-forming of the microspheres can be realized in one step. The thiophanate-methyl preparation prepared by taking the porous drug-loaded microspheres as the raw material not only has excellent water solubility and wettability, but also has the functions of slow release and pyrolysis resistance due to the combination of coating and micropores, the utilization rate of thiophanate-methyl is increased, and the raw material components have excellent biocompatibility and environmental friendliness, so that the thiophanate-methyl preparation has good application prospects. The sustainable development of agriculture is facilitated.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pesticide preparation, and particularly relates to a production process of a water-soluble thiophanate-methyl preparation. BACKGROUND

[0002] Thiophanate-methyl is a benzimidazole fungicide, also known as tolylfluanid, and is a broad-spectrum systemic low-toxicity fungicide with systemic, preventive and therapeutic effects. It is mainly used for preventing and treating diseases of vegetables, flowers, fruit trees and other crops.

[0003] The current dosage form of thiophanate-methyl mainly includes 50% or 70% wettable powder, 40% or 50% suspension concentrate and 36% suspension concentrate. Since thiophanate-methyl is almost insoluble in water (solubility <0.1 mg / L at 25℃), the traditional powder or suspension concentrate is prone to affecting the efficacy due to uneven dispersion. In the prior art, the water solubility is improved through a salt formation reaction (such as forming a sodium salt or a potassium salt with sodium / potassium hydroxide), but there are still certain technical defects.

[0004] Chinese patent with the publication number CN103430952A discloses a water-soluble thiophanate-methyl preparation and a production process thereof. Sodium hydroxide or potassium hydroxide is added to the raw material, and a solid-phase salt formation reaction is performed between thiophanate-methyl and sodium hydroxide or potassium hydroxide to form a sodium salt or a potassium salt of thiophanate-methyl. The salt has good solubility in water, and is used to improve the water solubility of the thiophanate-methyl preparation. However, since the preparation depends on strong alkali sodium hydroxide or potassium hydroxide, the pH value of the prepared preparation is alkaline, which can cause imbalance of the soil acid-base, and most crops grow in neutral or slightly acidic soil. Therefore, the use of the preparation can have potential negative effects on the soil and the environment. SUMMARY

[0005] The application aims to provide a production process of a water-soluble thiophanate-methyl preparation, which is simple, and the prepared water-soluble thiophanate-methyl preparation has excellent wetting and dispersing properties,

[0006] The application can be achieved by the following technical scheme.

[0007] The application provides a production process of a water-soluble thiophanate-methyl preparation, which includes the following steps.

[0008] Step one, dissolve chitosan in acetic acid solution, add polyethylene glycol monomethyl ether and a pore-forming agent, stir uniformly, then add thiophanate-methyl and stir uniformly to form a mixed solution;

[0009] Step two, add a crosslinking agent to the mixed solution, and perform spray drying through a spray dryer to obtain porous drug-loaded microspheres with a particle size of 5-10 μm;

[0010] Step three, the filler, viscosity reducer and wetting agent are stirred and mixed uniformly, and then crushed to a particle size of ≤10 μm. After crushing, the porous drug-loaded microspheres are stirred and mixed uniformly to obtain the water-soluble thiabendazole preparation.

[0011] In the above production process, chitosan and polyethylene glycol monomethyl ether are cross-linked under the action of a cross-linking agent to form polyethylene glycol modified chitosan. Chitosan is a natural polycationic polysaccharide, which has the characteristics of non-toxicity, biodegradability and regeneration. Chitosan itself has a certain hydrophilicity, but its wettability is usually poor. Polyethylene glycol is an amphiphilic biomaterial with hydrophilicity and flexibility. The hydroxyl group of polyethylene glycol can form a strong hydrogen bond with water molecules. Polyethylene glycol modified chitosan not only retains the advantages of chitosan, but also improves the water solubility and wettability.

[0012] Under the condition of giving polyethylene glycol modified chitosan high wettability and hydrophilicity, the methylthiabendazole is coated as a loading material to form a shell with high wettability and water solubility, breaking through the water solubility and wettability bottleneck of traditional methylthiabendazole wettable powder. And the polyethylene glycol modified chitosan coating layer will form a porous structure under the action of a porogen, increasing the contact area of the porous drug-loaded microspheres with water and further enhancing the wettability.

[0013] The spray drying method is a green and environmentally friendly preparation method. The porous drug-loaded microspheres prepared by the spray drying method have uniform particle size distribution and small particle size, and the granulation and poration of the microspheres can be realized in one step, which is simple and convenient. From the structure, the porous drug-loaded microspheres not only improve the water solubility and wettability, but also have the functions of sustained release and anti-pyrolysis due to the combination of coating and micropores, thereby improving the utilization rate and safety of pesticides and reducing the loss and residue of pesticides. It is suitable for modern agricultural scenarios such as unmanned aerial vehicle spraying.

[0014] The water-soluble thiabendazole preparation prepared by the above production process is coated with polyvinyl alcohol modified chitosan. When sprayed, chitosan will adhere to the surface of plant leaves, and the effective component methylthiabendazole will be released to the leaves through micropores to improve the efficacy. Chitosan can form a protective film to prevent pathogenic bacteria from invading and stimulate the secretion of defense substances (such as chitinase) by plants to enhance the disease resistance of plants. The raw materials of the preparation, polyethylene glycol and chitosan, have good biocompatibility and environmental friendliness, and will not cause environmental pollution.

[0015] Further, the concentration of the acetic acid solution is 1-5 wt%, and the mass ratio of chitosan to acetic acid solution is 1-3:100.

[0016] Further, the pore-forming agent is one of ammonium bicarbonate and sodium bicarbonate. The gas-type pore-forming agent mainly leaves pores in the material by decomposing or evaporating under high temperature or chemical reaction conditions. Ammonium bicarbonate generally completely decomposes at 60℃, has good decomposition performance, and the decomposition product has no residue, which does not negatively affect the final material. Sodium bicarbonate starts to decompose above 50℃, and the decomposition product is carbon dioxide and water. The residual sodium carbonate can also solidify the chitosan microspheres by forming acetate groups after adding acetic acid to neutralize chitosan.

[0017] Further, the mass ratio of the polyethylene glycol monomethyl ether and the chitosan is 1-2:5. By reacting formaldehyde with the amino groups in the chitosan to form Schiff bases, and by using the terminal hydroxyl groups of the polyethylene glycol monomethyl ether to undergo condensation reaction with formaldehyde to form a cross-linked network structure, the polyethylene glycol modified chitosan is achieved. The introduction of polyethylene glycol improves the water solubility and hydrophilicity of chitosan, so that it can exist in the form of stable colloids or particles in an aqueous solution.

[0018] Further, the mass-to-volume ratio of the pore-forming agent and the acetic acid solution is 0.1-0.2 g / mL.

[0019] Further, the mass ratio of the thiophanate-methyl and the chitosan is 4-5:3.

[0020] Further, the cross-linking agent is a 1-2wt% formaldehyde aqueous solution or a 0.1-2wt% glutaraldehyde aqueous solution, and the volume ratio of the cross-linking agent to the mixed solution is 1-5:100.

[0021] Further, the inlet air temperature of the spray drying is 120-160℃.

[0022] Further, the filler is one of kaolin, diatomite, and bentonite.

[0023] The viscosity-reducing agent is fumed white carbon black. Fumed white carbon black is a small-particle-size silicon dioxide. Due to its small particle size, it has a large specific surface area, strong surface adsorption, large surface energy, high chemical purity, good dispersion performance, and smooth surface. When the water-soluble thiophanate-methyl preparation is dispersed in water, it can reduce the frictional resistance between the molecular chains of chitosan, reduce the internal friction of the solution, and thus reduce the viscosity.

[0024] The wetting agent is one of alkyl polyglycoside and polyoxyethylene ether surfactant. Alkyl polyglycoside and polyoxyethylene ether surfactant belong to non-ionic surfactants, have good wetting properties, contain multiple hydrophilic groups (such as polyoxyethylene chains) in their molecular structures, can reduce the surface tension of liquids, make liquids more easily penetrate the surface of particles, and are easily biodegradable and environmentally friendly.

[0025] Further, the mass ratio of the drug-loaded microspheres, the filler, the viscosity reducer and the wetting agent is 200:2-4:3-5:1-3.

[0026] Advantages of the present application:

[0027] (1) The present application realizes cross-linking of chitosan and polyethylene glycol monomethyl ether under the action of a cross-linking agent to form polyethylene glycol modified chitosan, which is used to coat thiophanate-methyl to form porous drug-loaded microspheres with high wettability, high water solubility and high drug loading capacity. The thiophanate-methyl preparation prepared from the porous drug-loaded microspheres not only has excellent water solubility and wettability, but also has the functions of sustained release and anti-pyrolysis due to the combination of coating and micropores, thereby improving the utilization rate.

[0028] (2) The porous drug-loaded microspheres are prepared by a spray drying method, have uniform particle size distribution and small particle size, and can realize one-step granulation and poration of the microspheres under the synergistic action of the porogen. The process is simple. In the preparation of the thiophanate-methyl preparation, the filler, the viscosity reducer and the wetting agent are first broken, and then mixed with the porous drug-loaded microspheres with small particle size, so as to ensure the integrity of the structure of the porous drug-loaded microspheres.

[0029] (3) The raw material components of the thiophanate-methyl preparation of the present application have excellent biocompatibility and environmental friendliness, are high-efficiency, low-toxicity and sustainable, do not cause environmental pollution, prevent and control pests and diseases while avoiding agricultural pollution, and are conducive to the sustainable development of agriculture. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present application will be described clearly and completely below in combination with the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0031] Embodiment 1

[0032] Step one, chitosan is weighed and dissolved in 1wt% acetic acid solution, the mass ratio of chitosan to acetic acid solution is 1:100, polyethylene glycol monomethyl ether and ammonium bicarbonate are added, the mass ratio of polyethylene glycol monomethyl ether to chitosan is 1:5, the mass-volume ratio of ammonium bicarbonate to acetic acid solution is 0.1g / mL, and stirring is uniform, then thiophanate-methyl is added and stirred uniformly, the mass ratio of thiophanate-methyl to chitosan is 4:3, to form a mixed solution;

[0033] Step two, 1wt% formaldehyde aqueous solution is added to the mixed solution, the volume ratio of formaldehyde aqueous solution to mixed solution is 1:100, and spray drying is performed by a spray dryer, the inlet air temperature is set to 140℃, to obtain porous drug-loaded microspheres with a particle size of 5-10μm;

[0034] Step three, kaolin, fumed silica and alkyl polyglycoside were stirred and mixed uniformly, and were crushed by a pulverizer to a particle size of ≤10 μm. After crushing, the porous drug-loaded microspheres were stirred and mixed uniformly with the crushed kaolin, fumed silica and alkyl polyglycoside. The mass ratio of the drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside was 200:2:3:1. Thus, a water-soluble thiabendazole preparation was obtained.

[0035] Example 2

[0036] The difference from Example 1 is that the mass ratio of polyethylene glycol monomethyl ether and chitosan is 1.5:5, and the volume ratio of formaldehyde aqueous solution and mixed solution is 3:100. The specific steps are as follows:

[0037] Step one, chitosan was weighed and dissolved in 1wt% acetic acid solution. The mass ratio of chitosan to acetic acid solution was 1:100. Polyethylene glycol monomethyl ether and ammonium bicarbonate were added. The mass ratio of polyethylene glycol monomethyl ether to chitosan was 1.5:5. The mass-volume ratio of ammonium bicarbonate to acetic acid solution was 0.1 g / mL. After stirring uniformly, thiabendazole was added and stirred uniformly. The mass ratio of thiabendazole to chitosan was 4:3. A mixed solution was formed.

[0038] Step two, 1wt% formaldehyde aqueous solution was added to the mixed solution. The volume ratio of formaldehyde aqueous solution to mixed solution was 3:100. Spray drying was performed by a spray dryer. The inlet air temperature was set to 140°C. Porous drug-loaded microspheres were obtained. The particle size was 5-10 μm.

[0039] Step three, kaolin, fumed silica and alkyl polyglycoside were stirred and mixed uniformly, and were crushed by a pulverizer to a particle size of ≤10 μm. After crushing, the porous drug-loaded microspheres were stirred and mixed uniformly with the crushed kaolin, fumed silica and alkyl polyglycoside. The mass ratio of the drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside was 200:2:3:1. Thus, a water-soluble thiabendazole preparation was obtained.

[0040] Example 3

[0041] The difference from Example 1 is that the mass ratio of polyethylene glycol monomethyl ether and chitosan is 2:5, and the volume ratio of formaldehyde aqueous solution and mixed solution is 5:100. The specific steps are as follows:

[0042] Step one, chitosan was weighed and dissolved in 1wt% acetic acid solution. The mass ratio of chitosan to acetic acid solution was 1:100. Polyethylene glycol monomethyl ether and ammonium bicarbonate were added. The mass ratio of polyethylene glycol monomethyl ether to chitosan was 2:5. The mass-volume ratio of ammonium bicarbonate to acetic acid solution was 0.1 g / mL. After stirring uniformly, thiabendazole was added and stirred uniformly. The mass ratio of thiabendazole to chitosan was 4:3. A mixed solution was formed.

[0043] Step two, add 1wt% formaldehyde solution to the mixed solution, the volume ratio of formaldehyde solution and mixed solution is 5:100, spray drying through the spray dryer, set the inlet temperature to 140℃, get porous drug-loaded microspheres, particle size is 5-10μm;

[0044] Step three, mix kaolin, fumed silica and alkyl polyglycoside uniformly, crush to particle size ≤10μm with a crusher, mix the crushed porous drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside uniformly, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:2:3:1, get water-soluble thiabendazole preparation.

[0045] Example 4

[0046] The difference from example 2 is that the mass ratio of thiabendazole and chitosan is 5:3, the specific steps are as follows:

[0047] Step one, weigh chitosan and dissolve it in 1wt% acetic acid solution, the mass ratio of chitosan and acetic acid solution is 1:100, add polyethylene glycol monomethyl ether and ammonium bicarbonate, the mass ratio of polyethylene glycol monomethyl ether and chitosan is 1.5:5, the mass-volume ratio of ammonium bicarbonate and acetic acid solution is 0.1g / mL, stir uniformly, then add thiabendazole and stir uniformly, the mass ratio of thiabendazole and chitosan is 5:3, form a mixed solution;

[0048] Step two, add 1wt% formaldehyde solution to the mixed solution, the volume ratio of formaldehyde solution and mixed solution is 3:100, spray drying through the spray dryer, set the inlet temperature to 140℃, get porous drug-loaded microspheres, particle size is 5-10μm;

[0049] Step three, mix kaolin, fumed silica and alkyl polyglycoside uniformly, crush to particle size ≤10μm with a crusher, mix the crushed porous drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside uniformly, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:2:3:1, get water-soluble thiabendazole preparation.

[0050] Example 5

[0051] The difference from example 2 is that the mass ratio of thiabendazole and chitosan is 5:3, the specific steps are as follows:

[0052] Step one, weigh chitosan and dissolve it in 1wt% acetic acid solution, the mass ratio of chitosan and acetic acid solution is 1:100, add polyethylene glycol monomethyl ether and ammonium bicarbonate, the mass ratio of polyethylene glycol monomethyl ether and chitosan is 1.5:5, the mass-volume ratio of ammonium bicarbonate and acetic acid solution is 0.1g / mL, stir uniformly, then add thiabendazole and stir uniformly, the mass ratio of thiabendazole and chitosan is 5:3, form a mixed solution;

[0053] Step two, add 1wt% formaldehyde solution to the mixed solution, the volume ratio of formaldehyde solution and mixed solution is 3:100, spray drying through the spray dryer, set the inlet temperature to 140℃, get porous drug-loaded microspheres, particle size is 5-10μm;

[0054] Step three, mix kaolin, fumed silica and alkyl polyglycoside uniformly, crush to particle size ≤10μm with a crusher, mix with porous drug-loaded microspheres after crushing, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:2:3:1, get water-soluble thiophanate-methyl preparation.

[0055] Example 6

[0056] The difference from example 4 is only that the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:3:4:2, the specific steps are as follows:

[0057] Step one, weigh chitosan and dissolve in 1wt% acetic acid solution, the mass ratio of chitosan and acetic acid solution is 1:100, add polyethylene glycol monomethyl ether and ammonium bicarbonate, the mass ratio of polyethylene glycol monomethyl ether and chitosan is 1.5:5, the mass-volume ratio of ammonium bicarbonate and acetic acid solution is 0.1g / mL, stir uniformly, then add thiophanate-methyl and stir uniformly, the mass ratio of thiophanate-methyl and chitosan is 4.5:3, form a mixed solution;

[0058] Step two, add 1wt% formaldehyde solution to the mixed solution, the volume ratio of formaldehyde solution and mixed solution is 3:100, spray drying through the spray dryer, set the inlet temperature to 140℃, get porous drug-loaded microspheres, particle size is 5-10μm;

[0059] Step three, mix kaolin, fumed silica and alkyl polyglycoside uniformly, crush to particle size ≤10μm with a crusher, mix with porous drug-loaded microspheres after crushing, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:3:4:2, get water-soluble thiophanate-methyl preparation.

[0060] Example 7

[0061] The difference from example 4 is only that the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:4:5:3, the specific steps are as follows:

[0062] Step one, take chitosan and dissolve it in 1wt% acetic acid solution, the mass ratio of chitosan to acetic acid solution is 1:100, add polyethylene glycol monomethyl ether and ammonium bicarbonate, the mass ratio of polyethylene glycol monomethyl ether to chitosan is 1.5:5, the mass-volume ratio of ammonium bicarbonate to acetic acid solution is 0.1g / mL, stir evenly, then add thiophanate-methyl and stir evenly, the mass ratio of thiophanate-methyl to chitosan is 4.5:3, to form a mixed solution;

[0063] Step two, add 1wt% formaldehyde aqueous solution to the mixed solution, the volume ratio of formaldehyde aqueous solution to mixed solution is 3:100, spray drying is carried out by a spray dryer, the inlet air temperature is set to 140℃, to obtain porous drug-loaded microspheres with a particle size of 5-10μm;

[0064] Step three, stir and mix kaolin, fumed silica and alkyl polyglycoside uniformly, crush to a particle size of ≤10μm, then stir and mix with the porous drug-loaded microspheres, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:4:5:3, to obtain a water-soluble thiophanate-methyl preparation.

[0065] Example 8

[0066] The difference from Example 6 is that ammonium bicarbonate is replaced by sodium bicarbonate, and the specific steps are as follows:

[0067] Step one, take chitosan and dissolve it in 1wt% acetic acid solution, the mass ratio of chitosan to acetic acid solution is 1:100, add polyethylene glycol monomethyl ether and ammonium bicarbonate, the mass ratio of polyethylene glycol monomethyl ether to chitosan is 1.5:5, the mass-volume ratio of ammonium bicarbonate to acetic acid solution is 0.1g / mL, stir evenly, then add thiophanate-methyl and stir evenly, the mass ratio of thiophanate-methyl to chitosan is 4.5:3, to form a mixed solution;

[0068] Step two, add 1wt% formaldehyde aqueous solution to the mixed solution, the volume ratio of formaldehyde aqueous solution to mixed solution is 3:100, spray drying is carried out by a spray dryer, the inlet air temperature is set to 140℃, to obtain porous drug-loaded microspheres with a particle size of 5-10μm;

[0069] Step three, stir and mix kaolin, fumed silica and alkyl polyglycoside uniformly, crush to a particle size of ≤10μm, then stir and mix with the porous drug-loaded microspheres, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:3:4:2, to obtain a water-soluble thiophanate-methyl preparation.

[0070] Comparative Example 1

[0071] The difference from Example 1 is that polyethylene glycol monomethyl ether is not added in Step one, and the specific steps are as follows:

[0072] Step one, take chitosan and dissolve it in 1wt% acetic acid solution, the mass ratio of chitosan to acetic acid solution is 1:100, add ammonium bicarbonate, the mass-volume ratio of ammonium bicarbonate to acetic acid solution is 0.1g / mL, stir evenly, then add thiophanate-methyl and stir evenly, the mass ratio of thiophanate-methyl to chitosan is 4:3, to form a mixed solution;

[0073] Step two, add 1wt% formaldehyde aqueous solution to the mixed solution, the volume ratio of formaldehyde aqueous solution to mixed solution is 1:100, spray drying is carried out by a spray dryer, the inlet air temperature is set to 140℃, to obtain porous drug-loaded microspheres with a particle size of 5-10μm;

[0074] Step three, mix kaolin, fumed silica and alkyl polyglycoside evenly, crush them to a particle size of ≤10μm with a pulverizer, then mix them with the porous drug-loaded microspheres evenly, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:2:3:1, to obtain a water-soluble thiophanate-methyl preparation.

[0075] Comparative example 2

[0076] The difference from example 1 is that no pore-forming agent is added in step one, the specific steps are as follows:

[0077] Step one, take chitosan and dissolve it in 1wt% acetic acid solution, the mass ratio of chitosan to acetic acid solution is 1:100, add polyethylene glycol monomethyl ether, the mass ratio of polyethylene glycol monomethyl ether to chitosan is 1:5, stir evenly, then add thiophanate-methyl and stir evenly, the mass ratio of thiophanate-methyl to chitosan is 4:3, to form a mixed solution;

[0078] Step two, add 1wt% formaldehyde aqueous solution to the mixed solution, the volume ratio of formaldehyde aqueous solution to mixed solution is 1:100, spray drying is carried out by a spray dryer, the inlet air temperature is set to 140℃, to obtain drug-loaded microspheres with a particle size of 5-10μm;

[0079] Step three, mix kaolin, fumed silica and alkyl polyglycoside evenly, crush them to a particle size of ≤10μm with a pulverizer, then mix them with the drug-loaded microspheres evenly, the mass ratio of drug-loaded microspheres, kaolin, fumed silica and alkyl polyglycoside is 200:2:3:1, to obtain a water-soluble thiophanate-methyl preparation.

[0080] Comparative example 3

[0081] The difference from example 1 is that thiophanate-methyl technical material is directly used to prepare the thiophanate-methyl preparation, and the thiophanate-methyl technical material is added according to a mass proportion of 50%, the specific steps are as follows:

[0082] The thiophanate-methyl, kaolin, fumed white carbon black and alkyl polyglycoside are stirred and mixed uniformly, and are crushed by a pulverizer to a particle size of 10 μm or less, and are stirred and mixed uniformly again after crushing, and the mass ratio of the thiophanate-methyl, kaolin, fumed white carbon black and alkyl polyglycoside is 6:2:3:1, to obtain a water-soluble thiophanate-methyl preparation.

[0083] The thiophanate-methyl preparations prepared in Examples 1-8 and Comparative Examples 1-3 are subjected to performance testing, and the results are shown in Table 1:

[0084] The wetting time, the suspension rate, the pH value, the thiophanate-methyl mass fraction and the thermal storage stability are determined according to the reference standard GB / T 23552-2009 Thiophanate-methyl Wettable Powder.

[0085] Table 1

[0086] Item Wetting time / s Suspension rate / % pH value Thioph. mass fraction / % Thermal storage stability / % Example 1 63 82 6.1 51.1 99 Example 2 54 86 6.2 49.3 99 Example 3 52 87 6.3 47.6 99 Example 4 55 85 6.2 51.9 99 Example 5 59 83 6.2 52.2 99 Example 6 49 91 6.2 51.0 99 Example 7 51 89 6.2 50.3 99 Example 8 48 86 6.4 51.1 99 Comparative Example 1 94 75 6.0 45.7 97 Comparative Example 2 75 79 5.8 51.2 99 Comparative Example 3 115 54 7.0 50.0 97

[0087] As can be seen from Table 1, the thiophanate-methyl preparation prepared in the examples has a short wetting time, a high suspension rate, and excellent thermal decomposition resistance based on the coating effect, and the pH value is weakly acidic, which does not cause an alkaline burden on the soil.

[0088] It should be noted that the relational terms herein such as first and second, and the like are used merely to distinguish one entity or action from another entity or action, without necessarily requiring or implying that the entities or actions are in any way mutually exclusive or in any way arranged or ordered in succession.

[0089] Although the embodiments of the present application have been shown and described, it is understood that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A process for the production of a water-soluble thiabendazole formulation, characterized by, The method comprises the following steps: Step one, dissolve chitosan in acetic acid solution, add polyethylene glycol monomethyl ether and pore-forming agent, stir evenly, then add thiophanate-methyl and stir evenly to form a mixture; Step two, add crosslinking agent to the mixture, and spray dry through a spray dryer to obtain porous drug-loaded microspheres with a particle size of 5-10 μm; Step three, mix the filler, viscosity reducer and wetting agent evenly, crush them to a particle size of ≤10 μm with a crusher, and then mix them with the porous drug-loaded microspheres to obtain a water-soluble thiophanate-methyl preparation.

2. The production process of a water-soluble thiophanate-methyl formulation according to claim 1, characterized in that, The concentration of the acetic acid solution is 1-5 wt%, and the mass ratio of chitosan to the acetic acid solution is 1-3:

100.

3. The production process of a water-soluble thiophthalimide preparation according to claim 1, characterized in that, The pore-forming agent is one of ammonium bicarbonate and sodium bicarbonate.

4. The production process of a water-soluble thiophthalimide preparation according to claim 1, characterized by, The mass ratio of polyethylene glycol monomethyl ether to chitosan is 1-2:

5.

5. The production process of a water-soluble thiophthalimide preparation according to claim 1, characterized by, The mass-volume ratio of the pore-forming agent to the acetic acid solution is 0.1-0.2 g / mL.

6. The production process of a water-soluble thiophthalimide preparation according to claim 1, characterized by, The mass ratio of thiophanate-methyl to chitosan is 4-5:

3.

7. The production process of a water-soluble thiophthalimide preparation according to claim 1, characterized by, The crosslinking agent is 1-2 wt% formaldehyde aqueous solution or 0.1-2 wt% glutaraldehyde aqueous solution, and the volume ratio of the crosslinking agent to the mixture is 1-5:

100.

8. The process for producing a water-soluble thiophthalimide preparation according to claim 1, characterized by, The inlet air temperature of the spray drying is 120-160℃.

9. The production process of a water-soluble thiophthalimide preparation according to claim 1, characterized by, The filler is one of kaolin, diatomite and bentonite; The viscosity reducer is fumed white carbon black; The wetting agent is one of alkyl polyglycoside and polyoxyethylene ether surfactant.

10. The process for producing a water-soluble thiabendazole formulation according to claim 1, characterized by, The mass ratio of the drug-loaded microspheres, the filler, the viscosity reducer and the wetting agent is 200:2-4:3-5:1-3.