Long-acting rain-resistant bactericidal suspension agent and preparation method thereof

Abstract

The application discloses a rain-erosion-resistant long-acting bactericidal suspension agent and a preparation method thereof, and belongs to the technical field of pesticides. First, zinc nitrate hexahydrate, copper chloride dihydrate and 2-methyl imidazole are used to synthesize zinc-copper bimetal ZIF, and propiconazole and prochloraz are loaded on the ZIF to obtain a drug-loaded powder. Then, a metal-polyphenol network is formed by using gallic acid and iron ions to obtain a pre-coated drug-loaded powder. The pre-coated drug-loaded powder is used as a wall material to obtain a slow-release microcapsule powder through an interfacial polymerization method. Finally, the slow-release microcapsule powder is compounded with a dispersant SP-2206, magnesium aluminum silicate, xanthan gum, glycerol, kathon, a surfactant SP-4026SJ and deionized water, and is stirred and adjusted in pH value to obtain the rain-erosion-resistant long-acting bactericidal suspension agent. The preparation encapsulation rate, rain-erosion resistance and high-temperature storage stability are greatly improved, the slow release of the pesticide is realized, and the bactericidal duration is significantly prolonged.

Description

Technical Field

[0001] This invention belongs to the field of pesticide technology, specifically relating to a long-acting bactericidal suspension that is resistant to rain washout and its preparation method. Background Technology

[0002] Traditional pesticides suffer from problems such as easy photodegradation, short effective period, low utilization rate, easy loss and high environmental risk, which has promoted the application of microcapsule suspension technology in the pesticide field. This formulation encapsulates the active ingredient through a polymer capsule wall, achieving slow and controlled release, protecting the original pesticide, prolonging the effective period and reducing phytotoxicity.

[0003] Propiconazole and prochloraz are often used in combination in agricultural production. Their fungicidal spectra are complementary. Propiconazole has systemic properties and can control diseases such as sheath blight and rice blast, while prochloraz is effective against anthracnose and rice false smut. The combination formulation is mostly applied by spraying at the heading stage of rice or the early stage of fruit and vegetable diseases. However, propiconazole has a strong hydrophobic surface, which can easily lead to uneven dispersion and poor leaf adhesion. Prochloraz is easily photodegraded, resulting in rapid decline in efficacy in the field. If the microcapsules are not uniformly coated after the combination, the release rates may be mismatched, affecting the efficacy and increasing the risk of residues. At the same time, the use of the combination at the sensitive stage of crops may also cause phytotoxicity such as growth inhibition. Microencapsulation technology can effectively improve the above defects and improve the stability and field utilization of the agent.

[0004] Chinese invention patent application CN118126292A discloses a pesticide microcapsule suspension and its preparation method. The method uses interfacial polymerization, in which the pesticide technical and modified isoflurane diisocyanate are dissolved in an organic solvent as the oil phase, mixed and emulsified with an aqueous phase containing emulsifier and dispersant, and then a chain extender is added dropwise for cross-linking and curing to form polyurethane microcapsules. This method has the advantages of improving pesticide stability, reducing toxicity, and achieving sustained and controlled release.

[0005] However, the above scheme has a simple core structure, which only dissolves pesticides in the oil phase, which can easily lead to slow initial release and poor fast-acting effect. When compounded at high concentrations, it is easy to crystallize and precipitate. Moreover, the single space cannot separate the fast-acting and long-acting time sequence of the same pesticide, and long-term use can easily induce pesticide resistance. Summary of the Invention

[0006] The purpose of this invention is to provide a long-acting bactericidal suspension that is resistant to rain washout and its preparation method, so as to solve the problems in the prior art where the single core structure easily leads to slow initial release and poor rapid effect, and the single space cannot achieve the separation of the rapid and long-acting time sequence of the same pesticide, and long-term use easily leads to drug resistance.

[0007] The objective of this invention can be achieved through the following technical solutions: A method for preparing a long-lasting bactericidal suspension resistant to rain washout includes the following steps: Step 1: Zinc-copper bimetallic ZIF was synthesized using zinc nitrate hexahydrate, copper chloride dihydrate, and 2-methylimidazole. Propiconazole and imazalil technical were then loaded onto the ZIF to obtain a drug-loaded powder.

[0008] Step 2: Gallic acid and iron ions form a metal-polyphenol network to obtain a pre-coated drug-loaded powder. Then, using interfacial polymerization with polyurea as the wall material, a sustained-release microcapsule powder is obtained.

[0009] Step 3: Combine the sustained-release microcapsule powder with dispersant SP-2206, magnesium aluminum silicate, xanthan gum, glycerol, Kathon, surfactant SP-4026SJ, and deionized water, stir and adjust the pH value to obtain a long-lasting bactericidal suspension resistant to rain washout.

[0010] Furthermore, the specific preparation method of zinc-copper bimetallic ZIF is as follows: Zinc nitrate hexahydrate and copper chloride dihydrate were dissolved in deionized water to obtain a metal salt solution. 2-methylimidazole was dissolved in deionized water, and then the metal salt solution was added. The mixture was magnetically stirred at 35-45℃ and 600-800 rpm for 5-6 hours, centrifuged at 9000-10000 rpm for 10-20 minutes, filtered, and the precipitate was collected. The precipitate was washed 3-5 times each with deionized water and ethanol, and then vacuum dried to constant weight to obtain zinc-copper bimetallic ZIF.

[0011] Furthermore, the ratio of zinc nitrate hexahydrate, copper chloride dihydrate, and deionized water is 90-120g: 34-46g: 5000-6000mL.

[0012] Furthermore, the ratio of 2-methylimidazole, deionized water, and metal salt solution is 328-360g: 5000-6000mL: 5000-6000mL.

[0013] Furthermore, the specific preparation method of the drug-loaded powder is as follows: Zinc-copper bimetallic ZIF was dispersed in acetonitrile, and propiconazole technical, imazalil technical, and sodium dodecyl sulfate were added. The mixture was stirred at 35-45℃ in the dark for 12-14 h, during which time it was sonicated at 40-60 kHz for 5-10 min every 2 h, and centrifuged at 9000-10000 rpm for 10-20 min. The mixture was filtered, the precipitate was collected, and the precipitate was washed with ethanol 3-5 times and dried under vacuum to constant weight to obtain the drug-loaded powder.

[0014] Furthermore, the dosage ratio of zinc-copper bimetallic ZIF, acetonitrile, propiconazole technical, imazalil technical and sodium dodecyl sulfate is 500-580g: 2000-2800mL: 40-50g: 110-130g: 50-80mg.

[0015] Furthermore, the specific preparation method of the pre-coated drug-loaded powder is as follows: The drug-loaded powder was ultrasonically dispersed in deionized water and magnetically stirred at 750-850 rpm for 15-30 min. Polyvinylpyrrolidone was then added, and stirring was continued for 30-40 min. The pH was adjusted to 8 with sodium hydroxide solution, and 7 mg / mL gallic acid ethanol solution was slowly added dropwise while stirring was maintained. After the addition was complete, 70 mg / mL ferric chloride hexahydrate aqueous solution was slowly added. After the addition was complete, stirring was continued at 25-35℃ for 20-30 min. The mixture was vortexed for 1-3 min and centrifuged at 12000-15000 rpm for 10-20 min. The mixture was filtered, and the precipitate was collected. The precipitate was washed 3-5 times with deionized water and vacuum dried to constant weight to obtain the pre-coated drug-loaded powder.

[0016] Furthermore, the ratio of the amount of drug-loaded powder, deionized water, polyvinylpyrrolidone, gallic acid ethanol solution, and ferric chloride hexahydrate aqueous solution is 500-580g: 560-640mL: 2.4-3.6g: 60-80mL: 12-18mL.

[0017] Furthermore, the specific preparation method of the sustained-release microcapsule powder is as follows: Emulsifier SP-27001, 3wt% xanthan gum aqueous solution and organosilicon defoamer were added to deionized water, heated to 65-75℃ and stirred evenly to obtain the aqueous phase; The pre-coated drug powder was ultrasonically dispersed in a 50 vol% cyclohexanone / xylene mixed solvent, and then propiconazole technical, imazalil technical and diphenylmethane diisocyanate were added and mixed to obtain the oil phase. The oil phase was slowly added to the aqueous phase, and the mixture was sheared at 12000-13000 rpm for 5-10 min to form a stable O / W emulsion. The emulsion was then transferred to a four-necked flask and stirred at 65-75℃ and 400-500 rpm. A 9 wt% aqueous solution of tetraethylenepentamine was slowly added dropwise. After the addition was complete, the mixture was stirred at 65-75℃ for 5-6 h. After cooling, the mixture was centrifuged at 9000-10000 rpm for 10-20 min, and the precipitate was collected. The precipitate was washed 3-5 times with deionized water and dried to constant weight to obtain sustained-release microcapsule powder.

[0018] Furthermore, the ratio of emulsifier SP-27001, xanthan gum aqueous solution, silicone defoamer and deionized water is 130-150g: 54-58g: 10-12g: 5500-6000mL.

[0019] Furthermore, the ratio of the amount of pre-coated drug powder, cyclohexanone / xylene mixed solvent, propiconazole technical, imazalil technical and diphenylmethane diisocyanate is 423-467g: 2080-3200mL: 50-60g: 130-150g: 94-110g.

[0020] Furthermore, the ratio of the oil phase, aqueous phase, and tetraethylenepentamine aqueous solution is 2300-2400 mL: 5500-6000 mL: 1040-1200 mL.

[0021] Furthermore, the specific preparation method of the rain-resistant, long-lasting bactericidal suspension is as follows: Dispersant SP-2206, thickener magnesium aluminum silicate, xanthan gum, antifreeze glycerol, preservative Kathon, surfactant SP-4026SJ, and sustained-release microcapsule powder were added to deionized water and stirred evenly. The mixture was then mechanically stirred at low speed (400-800 rpm) for 30-40 minutes to ensure uniform suspension of the microcapsules. The pH was adjusted to 6.5 with sodium hydroxide solution to obtain a long-lasting bactericidal suspension resistant to rain washout.

[0022] Furthermore, the ratio of dispersant SP-2206, thickener magnesium aluminum silicate, xanthan gum, antifreeze glycerol, preservative Kathon, surfactant SP-4026SJ, sustained-release microcapsule powder, and deionized water is 12-15g: 3-5g: 1-2g: 15-18g: 1-1.5g: 3-3.4g: 520-530g: 400-460mL.

[0023] The beneficial effects of this invention are: 1. This invention utilizes zinc-copper bimetallic ZIF as a highly efficient pesticide carrier. Leveraging its mesoporous structure and high pesticide loading capacity, it achieves efficient physical adsorption and stable loading of propiconazole and prochloraz. A dense surface protection layer (MPN) is then applied to the loaded ZIF, effectively inhibiting pesticide burst release, enhancing carrier structural stability, and further extending pesticide residual effect. Subsequently, the MPN-coated loaded ZIF, along with additionally added propiconazole and prochloraz technicals, are co-encapsulated in polyurea microcapsules, innovatively forming a dual-space, dual-drug composite core structure. This achieves synergistic enhancement of two fungicides with different mechanisms of action, significantly improving pesticide efficacy. The formulation exhibits a broad spectrum of bactericidal activity and high bactericidal efficacy. Furthermore, the scientifically formulated suspension system, enhanced with adjuvants such as dispersants, thickeners, and surfactants, provides excellent leaf adhesion and resistance to rain washout, reducing pesticide runoff after field application. The combination of slow-release ZIF mesoporous structures, rapid onset of action of free drug in the oil phase, and diffusion-controlled release via polyurea capsule walls creates a differentiated, tiered release mechanism, resulting in a formulation that is both fast-acting and long-lasting. This ensures a more stable and sustained release of the pesticide, significantly reducing the frequency of field application and lowering costs. Simultaneously, it effectively delays the development and progression of pathogen resistance, balancing the high efficiency, economy, and ecological benefits of pesticide application.

[0024] 2. The zinc-copper bimetallic ZIF of the present invention forms a multi-leaf cross structure through the coordination synergy of zinc-copper ions and 2-methylimidazole, which improves the specific surface area, pore volume and structural stability of the carrier, endowing it with high drug loading capacity and preventing structural collapse during processing; the bimetallic synergy optimizes the surface properties of ZIF, improves its interfacial compatibility with MPN coating layer and polyurea capsule wall, and lays the foundation for high encapsulation efficiency; zinc-copper ions also synergistically achieve physicochemical stability of the carrier, maintain the integrity of the pore structure, reduce pesticide leakage, and form a double protection with MPN coating layer to reduce pesticide decomposition; at the same time, the mesoporous and multi-leaf cross structure formed by the bimetallic synergy constructs pesticide slow-release channels and forms physical barriers, forming a double slow-release synergy with polyurea capsule wall, providing a guarantee for long-term sustained release of the formulation.

[0025] 3. The pre-coated pesticide powder of the present invention has an MPN coating layer that forms hydrogen bonds and coordination bonds with ZIF through phenolic hydroxyl groups, creating a dual-structure protection with the ZIF bimetallic framework. Combined with the anti-agglomeration effect of PVP, this avoids structural damage, particle agglomeration, and premature pesticide leakage during ZIF processing, thus improving overall physicochemical stability. The MPN layer optimizes the hydrophilicity and hydrophobicity of the ZIF surface, improving its interfacial compatibility with the oil-water phase and contributing to the high encapsulation rate of the polyurea capsule wall preparation. Furthermore, its polyphenol groups synergistically enhance the adhesion to the leaf wax layer through hydrogen bonds with the ZIF micro-nano structure, laying the core foundation for the formulation's resistance to rain washout. The ZIF mesoporous structure forms an initial barrier to pesticide diffusion, while the MPN layer forms a secondary physical barrier. The two also synergistically achieve dual pesticide protection with UV and thermal stability, reducing the decomposition and loss of active ingredients. At the same time, they synergistically regulate the pesticide diffusion rate, making the release more gradual, providing key support for the long-acting sustained-release bactericidal performance of the formulation.

[0026] 4. The sustained-release microcapsule powder of the present invention is composed of a polyurea capsule wall and a pre-coated drug-loaded powder, achieving synergistic effects among the polyurea capsule wall, MPN coating layer, and zinc-copper bimetallic ZIF. The polyurea capsule wall completely encapsulates the inner structure, forming a double-layer physical barrier with the MPN coating layer. Combined with the mesoporous barrier of the zinc-copper bimetallic ZIF, a three-stage sustained-release synergy is formed, precisely controlling the pesticide release rate and ensuring the long-lasting bactericidal effect of the formulation. The chemical stability of the polyurea capsule wall, together with the physicochemical stability of the MPN layer and the zinc-copper bimetallic ZIF, enhances the microcapsule's resistance to high temperature and shear, reduces pesticide decomposition and leakage, and ensures storage stability. The polyurea capsule wall also optimizes the microcapsule interface dispersibility, synergistically controlling the hydrophilicity and hydrophobicity of the MPN layer, avoiding particle aggregation or anchoring at the oil-water interface, significantly improving the pesticide encapsulation rate, and providing structural support for the hydrogen bonding adhesion between the MPN layer and the leaf wax layer. The three synergistically enhance the formulation's resistance to rain washout. Detailed Implementation

[0027] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments in the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0028] Example 1: A method for preparing a long-lasting bactericidal suspension resistant to rainwater runoff, comprising the following steps: S1: Dissolve 90g of zinc nitrate hexahydrate and 34g of copper chloride dihydrate in 5000mL of deionized water to obtain a metal salt solution; dissolve 328g of 2-methylimidazole in 5000mL of deionized water, then add 5000mL of the metal salt solution, stir magnetically at 35℃ and 600rpm for 5h, centrifuge at 9000rpm for 10min, filter, collect the precipitate, wash the precipitate three times each with deionized water and ethanol, and vacuum dry at 60℃ for 12h to obtain zinc-copper bimetallic ZIF.

[0029] Copper and zinc ions compete for coordination with 2-methylimidazole, inducing ligand loss, oxygen vacancies, and mesoporous structures, promoting the increase of interlayer hydrogen bonds, transforming the single-leaf structure into a stable multi-leaf cross structure, and endowing the material with high drug loading capacity.

[0030] S2: Disperse 500g of zinc-copper bimetallic ZIF in 2000mL of acetonitrile, add 40g of propiconazole technical, 110g of imazalil technical and 50mg of sodium dodecyl sulfate, stir at 35℃ in the dark for 12h, sonicate at 40kHz for 5min every 2h, centrifuge at 9000rpm for 10min, filter, collect the precipitate, wash the precipitate 3 times with ethanol, and vacuum dry at 40℃ for 12h to obtain drug-loaded powder.

[0031] By using solvent adsorption, pesticide molecules diffuse from the solvent into the porous structure of the carrier. Ultrasonic assistance improves mass transfer efficiency, shortens loading time, and avoids damage to the carrier structure.

[0032] S3: Disperse 500g of drug-loaded powder ultrasonically in 560mL of deionized water and stir magnetically at 750rpm for 15min. Then add 2.4g of polyvinylpyrrolidone and continue stirring for 30min. Adjust the pH to 8 with sodium hydroxide solution. Slowly add 60mL of 7mg / mL gallic acid ethanol solution while stirring. After the addition is complete, slowly add 12mL of 70mg / mL ferric chloride hexahydrate aqueous solution. After the addition is complete, continue stirring at 25℃ for 20min. Vortex for 1min and centrifuge at 12000rpm for 10min. Filter, collect the precipitate, wash the precipitate three times with deionized water, and vacuum dry at 40℃ for 12h to obtain pre-coated drug-loaded powder.

[0033] Under weakly alkaline conditions, the phenolic hydroxyl groups of gallic acid coordinate with iron ions to form a metal-polyphenol network, which is deposited on the ZIF surface. PVP acts as a stabilizer to prevent particle aggregation, while MPN can enhance adhesion to the leaf wax layer through hydrogen bonding and absorb ultraviolet light to improve photostability.

[0034] S4: Add 130g of emulsifier SP-27001, 54g of 3wt% xanthan gum aqueous solution and 10g of organosilicon defoamer to 5500mL of deionized water, heat to 65℃ and stir evenly to obtain the aqueous phase; 423g of pre-coated drug powder was ultrasonically dispersed in 2080mL of a 50vol% cyclohexanone / xylene mixed solvent, and 50g of propiconazole technical, 130g of imazalil technical and 94g of diphenylmethane diisocyanate were added and mixed well to obtain the oil phase. 2300 mL of the oil phase was slowly added to 5500 mL of the aqueous phase, and the mixture was sheared at 12000 rpm for 5 min to form a stable O / W emulsion. The emulsion was then transferred to a four-necked flask and stirred at 65 °C and 400 rpm. 1040 mL of 9 wt% tetraethylenepentamine aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred at 65 °C for 5 h. After cooling, the mixture was centrifuged at 9000 rpm for 10 min, and the precipitate was collected. The precipitate was washed three times with deionized water and dried to constant weight to obtain sustained-release microcapsule powder.

[0035] Using diphenylmethane diisocyanate as the oil phase wall material monomer and tetraethylenepentamine as the aqueous phase wall material monomer, a polyurea capsule wall is generated at the O / W emulsion interface through a condensation reaction. This completely encapsulates the pesticide-loaded powder coated with MPN, avoiding the problem of particles anchoring at the interface or entering the aqueous phase, resulting in a higher encapsulation rate.

[0036] S5: Add 12g of dispersant SP-2206, 3g of thickener magnesium aluminum silicate, 1g of xanthan gum, 15g of antifreeze glycerol, 1g of preservative Kathon, 3g of surfactant SP-4026SJ, and 520g of sustained-release microcapsule powder to 400mL of deionized water, stir evenly, and mechanically stir at low speed of 400rpm for 30min to make the microcapsules uniformly suspended. Adjust the pH value to 6.5 with sodium hydroxide solution to obtain a long-lasting bactericidal suspension that is resistant to rain washout.

[0037] Example 2: A method for preparing a long-lasting bactericidal suspension resistant to rainwater runoff, comprising the following steps: S1: Dissolve 105g of zinc nitrate hexahydrate and 40g of copper chloride dihydrate in 5500mL of deionized water to obtain a metal salt solution; dissolve 344g of 2-methylimidazole in 5500mL of deionized water, then add 5500mL of the metal salt solution, stir magnetically at 40℃ and 700rpm for 5.5h, centrifuge at 9500rpm for 15min, filter, collect the precipitate, wash the precipitate four times each with deionized water and ethanol, and vacuum dry at 65℃ for 13h to obtain zinc-copper bimetallic ZIF.

[0038] S2: 540g of zinc-copper bimetallic ZIF was dispersed in 2400mL of acetonitrile, and 45g of propiconazole technical, 120g of imazalil technical and 65mg of sodium dodecyl sulfate were added. The mixture was stirred at 40℃ in the dark for 13h, during which it was sonicated at 50kHz for 7.5min every 2h and centrifuged at 9500rpm for 15min. The mixture was filtered, the precipitate was collected, and the precipitate was washed 4 times with ethanol and dried under vacuum at 45℃ for 13h to obtain the drug-loaded powder.

[0039] S3: Disperse 540g of drug-loaded powder ultrasonically in 600mL of deionized water and stir magnetically at 800rpm for 22.5min. Add 3.0g of polyvinylpyrrolidone and continue stirring for 35min. Adjust the pH to 8 with sodium hydroxide solution. Slowly add 70mL of 7mg / mL gallic acid ethanol solution while stirring. After the addition is complete, slowly add 15mL of 70mg / mL ferric chloride hexahydrate aqueous solution. After the addition is complete, continue stirring at 30℃ for 25min. Vortex for 2min and centrifuge at 13500rpm for 15min. Filter, collect the precipitate, wash the precipitate 4 times with deionized water, and vacuum dry at 45℃ for 13h to obtain pre-coated drug-loaded powder.

[0040] S4: Add 140g of emulsifier SP-27001, 56g of 3wt% xanthan gum aqueous solution and 11g of organosilicon defoamer to 5750mL of deionized water, heat to 70℃ and stir evenly to obtain the aqueous phase; 445g of pre-coated drug powder was ultrasonically dispersed in 2640mL of a 50vol% cyclohexanone / xylene mixed solvent, and 55g of propiconazole technical, 140g of imazalil technical and 102g of diphenylmethane diisocyanate were added and mixed well to obtain the oil phase. 2350 mL of the oil phase was slowly added to 5750 mL of the aqueous phase, and the mixture was sheared at 12500 rpm for 7.5 min to form a stable O / W emulsion. The emulsion was then transferred to a four-necked flask and stirred at 70 °C and 450 rpm. 1120 mL of 9 wt% tetraethylenepentamine aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred at 70 °C for 5.5 h. After cooling, the mixture was centrifuged at 9500 rpm for 15 min, and the precipitate was collected. The precipitate was washed four times with deionized water and dried to constant weight to obtain sustained-release microcapsule powder.

[0041] S5: Add 13.5g of dispersant SP-2206, 4g of thickener magnesium aluminum silicate, 1.5g of xanthan gum, 16.5g of antifreeze glycerol, 1.25g of preservative Kathon, 3.2g of surfactant SP-4026SJ, and 525g of sustained-release microcapsule powder to 430mL of deionized water, stir evenly, and mechanically stir at low speed of 600rpm for 35min to make the microcapsules uniformly suspended. Adjust the pH value to 6.5 with sodium hydroxide solution to obtain a long-lasting bactericidal suspension that is resistant to rain washout.

[0042] Example 3: A method for preparing a long-lasting bactericidal suspension resistant to rainwater runoff, comprising the following steps: S1: Dissolve 120g of zinc nitrate hexahydrate and 46g of copper chloride dihydrate in 6000mL of deionized water to obtain a metal salt solution; dissolve 360g of 2-methylimidazole in 6000mL of deionized water, then add 6000mL of the metal salt solution, stir magnetically at 45℃ and 800rpm for 6h, centrifuge at 10000rpm for 20min, filter, collect the precipitate, wash the precipitate 5 times each with deionized water and ethanol, and vacuum dry at 70℃ for 14h to obtain zinc-copper bimetallic ZIF.

[0043] S2: 580g of zinc-copper bimetallic ZIF was dispersed in 2800mL of acetonitrile, and 50g of propiconazole technical, 130g of imazalil technical and 80mg of sodium dodecyl sulfate were added. The mixture was stirred at 45℃ in the dark for 14h, and sonicated at 60kHz for 10min every 2h during the process. The mixture was then centrifuged at 10000rpm for 20min, filtered, and the precipitate was collected. The precipitate was washed 5 times with ethanol and dried under vacuum at 50℃ for 14h to obtain the drug-loaded powder.

[0044] S3: Disperse 580g of drug-loaded powder ultrasonically in 640mL of deionized water and stir magnetically at 850rpm for 30min. Then add 3.6g of polyvinylpyrrolidone and continue stirring for 40min. Adjust the pH to 8 with sodium hydroxide solution. Slowly add 80mL of 7mg / mL gallic acid ethanol solution while stirring. After the addition is complete, slowly add 18mL of 70mg / mL ferric chloride hexahydrate aqueous solution. After the addition is complete, continue stirring at 35℃ for 30min. Vortex for 3min and centrifuge at 15000rpm for 20min. Filter, collect the precipitate, wash the precipitate 5 times with deionized water, and vacuum dry at 50℃ for 14h to obtain pre-coated drug-loaded powder.

[0045] S4: Add 150g of emulsifier SP-27001, 58g of 3wt% xanthan gum aqueous solution and 12g of organosilicon defoamer to 6000mL of deionized water, heat to 75℃ and stir evenly to obtain the aqueous phase; 467g of pre-coated drug powder was ultrasonically dispersed in 3200mL of a 50vol% cyclohexanone / xylene mixed solvent, and 60g of propiconazole technical, 150g of imazalil technical and 110g of diphenylmethane diisocyanate were added and mixed well to obtain the oil phase. 2400 mL of the oil phase was slowly added to 6000 mL of the aqueous phase, and the mixture was sheared at 13000 rpm for 10 min to form a stable O / W emulsion. The emulsion was then transferred to a four-necked flask and stirred at 75 °C and 500 rpm. 1200 mL of 9 wt% tetraethylenepentamine aqueous solution was slowly added dropwise. After the addition was complete, the mixture was stirred at 75 °C for 6 h. After cooling, the mixture was centrifuged at 10000 rpm for 20 min, and the precipitate was collected. The precipitate was washed five times with deionized water and dried to constant weight to obtain sustained-release microcapsule powder.

[0046] S5: Add 15g of dispersant SP-2206, 5g of thickener magnesium aluminum silicate, 2g of xanthan gum, 18g of antifreeze glycerol, 1.5g of preservative Kathon, 3.4g of surfactant SP-4026SJ, and 530g of sustained-release microcapsule powder to 460mL of deionized water, stir evenly, and mechanically stir at low speed of 800rpm for 40min to make the microcapsules uniformly suspended. Adjust the pH value to 6.5 with sodium hydroxide solution to obtain a long-lasting bactericidal suspension that is resistant to rain washout.

[0047] In Examples 1-3, zinc nitrate hexahydrate was selected from Hubei Rishengchang New Material Technology Co., Ltd., CAS No. 10196-18-6; copper chloride dihydrate was selected from Shandong Feihong New Material Co., Ltd., CAS No. 7447-39-4; 2-methylimidazole was selected from Shandong Xinyingshun New Material Co., Ltd., CAS No. 693-98-1; dichloromethane was selected from Shenyang Elepx Chemical Co., Ltd., CAS No. 75-09-2; propiconazole technical grade was selected from Hubei Deante Chemical Technology Co., Ltd., CAS No. 60207-90-1; imazalil technical grade was selected from Hubei Jiahuixingcheng Biotechnology Co., Ltd., CAS No. 67747-09-5; and sodium dodecyl sulfate was selected from Shanghai Zhenlishi Network Technology Co., Ltd., model EMAL. 10G-3; Polyvinylpyrrolidone was selected from Jinan Zhengkang Chemical Co., Ltd., model K30, CAS number 9003-39-8; Gallic acid was selected from Shandong Pingju Biotechnology Co., Ltd., CAS number 149-91-7; Ferric chloride hexahydrate was selected from Wuhan Hongde Yuexin Pharmaceutical Technology Co., Ltd., CAS number 10025-77-1; Emulsifier SP-27001 was selected from Jiangsu Qingyu Chemical Technology Co., Ltd.; Xanthan gum was selected from Shandong Huiheng Biotechnology Co., Ltd., CAS number 11138-66-2; Organosilicon defoamer was selected from Shandong Jiayi Chemical Technology Co., Ltd., model 01; Cyclohexanone was selected from Shandong Lukong Supply Chain Co., Ltd., CAS number 108-94-1; Xylene was selected from Shandong... Xinshunli Chemical Co., Ltd.; diphenylmethane diisocyanate was selected from Jiangsu Bosite Chemical Technology Co., Ltd., CAS No. 101-68-8; tetraethylenepentamine was selected from Pande (Shanghai) International Trade Co., Ltd., CAS No. 112-57-2; dispersant SP-2206 and surfactant SP-4026SJ were both selected from Tianjin Hepufeile New Materials Co., Ltd.; thickener magnesium aluminum silicate was selected from Jinan Huijinchuan Chemical Co., Ltd., CAS No. 71205-22-6; antifreeze glycerol was selected from Jinan Chenghao Chemical Co., Ltd., CAS No. 56-81; preservative Kathon was selected from Guangdong Fangxin Biotechnology Co., Ltd., CAS No. 55965-84-9; the remaining raw materials were all commercially available products.

[0048] Comparative Example 1: The difference from Example 1 is that steps S1 and S2 are omitted, and blank ZIF (prepared only from zinc ions and 2-methylimidazole, without introducing copper ions and without loading pesticides) is prepared. The pesticide-loaded powder in step S3 is replaced with an equal mass of blank ZIF for MPN coating. In the oil phase of step S4, the MPN-coated loaded ZIF is replaced with an equal mass of MPN-coated blank ZIF. The remaining steps remain unchanged, resulting in a long-lasting bactericidal suspension resistant to rain washout.

[0049] Comparative Example 2: The difference from Example 1 is that step S3 is omitted. In step S4, the pre-coated drug-loaded powder in step S4 is replaced with an equal mass of the drug-loaded powder obtained in step S2. The remaining steps remain unchanged, resulting in a long-lasting bactericidal suspension resistant to rain washout.

[0050] Comparative Example 3: The difference from Example 1 is that propiconazole and imazalil free active ingredients are not added in step S4, while the other steps remain unchanged, resulting in a long-lasting bactericidal suspension resistant to rain washout.

[0051] The following performance tests were conducted on the long-lasting bactericidal suspensions resistant to rainwater washout prepared in Examples 1-3 and Comparative Examples 1-3: Encapsulation efficiency: Following the determination method in HG / T 4939-2016 "Pesticide Microcapsules", 0.01g of suspension sample was added to 100mL of xylene, shaken well, and centrifuged to obtain the supernatant containing the free active ingredient outside the capsule. The supernatant was transferred to a 50mL volumetric flask and diluted to volume with anhydrous methanol. An appropriate amount of anhydrous methanol was added to the precipitate after centrifugation, and the mixture was ultrasonically broken up to completely dissolve the pesticide technical material inside the capsule. The volume was then diluted to volume with anhydrous methanol. The pesticide technical material content in the supernatant and precipitate was determined using high-performance liquid chromatography (HPLC). The encapsulation efficiency (%) was calculated using the formula: Encapsulation efficiency (%) = (1 - content of free active ingredient outside the capsule / total active ingredient) × 100%. A higher encapsulation efficiency indicates a better coating effect of the formulation on the pesticide technical material.

[0052] Cumulative Release: 1g of suspension sample was placed in a dialysis bag (molecular weight cutoff 3500 Da), sealed, and then placed in an Erlenmeyer flask containing 500mL of release medium (an aqueous solution containing 30wt% methanol). The mixture was stirred at a constant speed of 150rpm at room temperature. 5mL samples were taken at 6h, 24h, 48h, 72h, 96h, and 120h, with an equal volume of release medium added simultaneously at the same temperature. The pesticide technical content in the sample solution was determined using high-performance liquid chromatography (HPLC), and the cumulative release rate (%) at different time points was calculated. A smaller change in the cumulative release rate and a longer effective release period indicate better long-acting sustained-release performance of the formulation.

[0053] High-temperature storage stability: 50g of suspension sample was sealed in a brown sample bottle and stored in a constant temperature incubator at 54℃±2℃ for 14 days. After storage, it was taken out and cooled to room temperature. The appearance of the preparation was observed for abnormalities such as layering, precipitation, clumping, and demulsification. At the same time, 0.01g of the sample before and after storage were weighed and the content of active ingredients was determined by high performance liquid chromatography. The decomposition rate of active ingredients (%) was calculated according to the formula: (content of active ingredients before storage - content of active ingredients after storage) / content of active ingredients before storage × 100%. The lower the decomposition rate of active ingredients and the no abnormality in appearance, the better the high-temperature storage stability of the preparation.

[0054] The results are shown in Table 1: Table 1. Performance Test Results of Rain-Resistant Long-Lasting Bactericidal Suspension

[0055] As can be seen from Table 1, the rain-resistant long-lasting bactericidal suspensions prepared in Examples 1-3 of this invention are significantly better than Comparative Examples 1-3 in terms of encapsulation efficiency, cumulative release sustained-release properties, and high-temperature storage stability.

[0056] In Comparative Example 1, the encapsulation efficiency was significantly reduced, the cumulative release rate increased sharply, and the high-temperature storage stability was extremely poor. This may be because zinc-copper bimetallic ZIF was not prepared and pesticide loading was not performed. Only blank ZIF was used as a carrier. It has no mesoporous structure and poor drug loading capacity, so it cannot achieve effective pesticide loading and encapsulation. The polyurea capsule wall is also difficult to form a stable microcapsule structure, resulting in a sharp increase in the content of free pesticides outside the capsule. During storage, component decomposition and formulation stratification and clumping are likely to occur.

[0057] In Comparative Example 2, the encapsulation efficiency decreased, the cumulative release rate increased significantly, and the decomposition rate of the active ingredient increased. This may be because the drug-loaded powder was not coated with MPN, and the lack of protection and adhesion of the metal-polyphenol network not only made the ZIF carrier susceptible to damage during interfacial polymerization, reducing the pesticide encapsulation effect, but also left the microcapsule surface without a protective layer, which could not block the influence of the external environment, resulting in faster pesticide release and easy decomposition of the active ingredient during storage.

[0058] In Comparative Example 3, the cumulative release rate increased significantly, the long-acting sustained-release performance decreased, and the encapsulation rate also decreased slightly. This may be because no additional free active ingredients of propiconazole and imazalil were added in step S4. The pesticides loaded on the ZIF carrier lacked the gradient release coordination between the free active ingredients and the carrier-loaded pesticides. In addition, the content of active ingredients in the oil phase was insufficient, which prevented the polyurea microcapsules formed by interfacial polymerization from achieving a slow gradient release of the pesticides. This also slightly affected the encapsulation effect of the microcapsules, ultimately leading to a deterioration in the long-acting sustained-release performance of the formulation.

[0059] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the invention.

Claims

1. A method for preparing a rainfast long-acting bactericidal suspension, characterized in that, Includes the following steps: Step 1: Zinc-copper bimetallic ZIF was synthesized using zinc nitrate hexahydrate, copper chloride dihydrate, and 2-methylimidazole, and then loaded with propiconazole and imazalil technical to obtain a drug-loaded powder. Step 2: Gallic acid and iron ions form a metal-polyphenol network to obtain a pre-coated drug powder. Then, using interfacial polymerization with polyurea as the wall material, a sustained-release microcapsule powder is obtained. Step 3: Combine the sustained-release microcapsule powder with dispersant SP-2206, magnesium aluminum silicate, xanthan gum, glycerol, Kathon, surfactant SP-4026SJ, and deionized water, stir and adjust the pH value to obtain a long-lasting bactericidal suspension resistant to rain washout.

2. The method for preparing rainwater erosion resistant long-acting bactericidal suspension according to claim 1, characterized in that, The specific preparation method of the zinc-copper bimetallic ZIF is as follows: Zinc nitrate hexahydrate and copper chloride dihydrate were dissolved in deionized water to obtain a metal salt solution. 2-methylimidazole was dissolved in deionized water, and then the metal salt solution was added. The mixture was magnetically stirred at 35-45℃ and 600-800 rpm for 5-6 hours, centrifuged at 9000-10000 rpm for 10-20 minutes, filtered, and the precipitate was collected. The precipitate was washed 3-5 times each with deionized water and ethanol, and then vacuum dried to constant weight to obtain zinc-copper bimetallic ZIF.

3. The method for preparing rainwater erosion resistant long-acting bactericidal SC according to claim 2, characterized in that, The ratio of zinc nitrate hexahydrate, copper chloride dihydrate, and deionized water is 90-120g: 34-46g: 5000-6000mL; the ratio of 2-methylimidazole, deionized water, and metal salt solution is 328-360g: 5000-6000mL: 5000-6000mL.

4. The method for preparing rainwater erosion resistant long-acting bactericidal SC according to claim 1, characterized in that, The specific preparation method of the drug-loaded powder is as follows: Zinc-copper bimetallic ZIF was dispersed in acetonitrile, and propiconazole technical, imazalil technical, and sodium dodecyl sulfate were added. The mixture was stirred at 35-45℃ in the dark for 12-14 h, during which time it was sonicated at 40-60 kHz for 5-10 min every 2 h, and centrifuged at 9000-10000 rpm for 10-20 min. The mixture was filtered, the precipitate was collected, and the precipitate was washed with ethanol 3-5 times and dried under vacuum to constant weight to obtain the drug-loaded powder. The ratio of zinc-copper bimetallic ZIF, acetonitrile, propiconazole technical, imazalil technical and sodium dodecyl sulfate is 500-580g: 2000-2800mL: 40-50g: 110-130g: 50-80mg.

5. The method for preparing rain water erosion resistant long-acting bactericidal SC according to claim 1, characterized in that, The specific preparation method of the pre-coated drug-loaded powder is as follows: The drug-loaded powder was ultrasonically dispersed in deionized water and magnetically stirred at 750-850 rpm for 15-30 min. Polyvinylpyrrolidone was then added and stirred for 30-40 min. The pH was adjusted to 8 with sodium hydroxide solution. Under stirring, 7 mg / mL gallic acid ethanol solution was added dropwise. After the addition was complete, 70 mg / mL ferric chloride hexahydrate aqueous solution was added. The mixture was stirred at 25-35℃ for 20-30 min, vortexed for 1-3 min, and centrifuged at 12000-15000 rpm for 10-20 min. The mixture was filtered, the precipitate was collected, and the precipitate was washed 3-5 times with deionized water and vacuum dried to constant weight to obtain the pre-coated drug-loaded powder.

6. The method for preparing a rain-resistant, long-lasting bactericidal suspension according to claim 5, characterized in that, The ratio of the amount of drug-loaded powder, deionized water, polyvinylpyrrolidone, gallic acid ethanol solution, and ferric chloride hexahydrate aqueous solution is 500-580g: 560-640mL: 2.4-3.6g: 60-80mL: 12-18mL.

7. The method for preparing rainwater erosion resistant long-acting bactericidal SC according to claim 1, characterized in that, The specific preparation method of the sustained-release microcapsule powder is as follows: Emulsifier SP-27001, 3wt% xanthan gum aqueous solution and organosilicon defoamer were added to deionized water, heated to 65-75℃ and stirred evenly to obtain the aqueous phase; The pre-coated drug powder was ultrasonically dispersed in a 50 vol% cyclohexanone / xylene mixed solvent, and then propiconazole technical, imazalil technical and diphenylmethane diisocyanate were added and mixed to obtain the oil phase. The oil phase was slowly added to the aqueous phase, and sheared at 12000-13000 rpm for 5-10 min. The mixture was then transferred to a four-necked flask and 9 wt% tetraethylenepentamine aqueous solution was added dropwise under stirring at 65-75℃ and 400-500 rpm. After the addition was complete, the mixture was stirred for 5-6 h, cooled, and centrifuged at 9000-10000 rpm for 10-20 min. The precipitate was collected, washed 3-5 times with deionized water, and dried to constant weight to obtain sustained-release microcapsule powder.

8. The method for preparing rainwater erosion resistant long-acting bactericidal SC according to claim 7, characterized in that, The ratio of emulsifier SP-27001, xanthan gum aqueous solution, silicone defoamer and deionized water is 130-150g: 54-58g: 10-12g: 5500-6000mL; The ratio of the amount of the pre-coated drug powder, the cyclohexanone / xylene mixed solvent, the propiconazole technical, the imazalil technical and the diphenylmethane diisocyanate is 423-467g: 2080-3200mL: 50-60g: 130-150g: 94-110g. The ratio of the oil phase, aqueous phase, and tetraethylenepentamine aqueous solution is 2300-2400 mL: 5500-6000 mL: 1040-1200 mL.

9. The method for preparing the rainwater scouring resistant long-acting bactericidal SC according to claim 1, characterized in that, The specific preparation method of the rain-resistant, long-lasting bactericidal suspension is as follows: Dispersant SP-2206, thickener magnesium aluminum silicate, xanthan gum, antifreeze glycerol, preservative Kathon, surfactant SP-4026SJ and sustained-release microcapsule powder were added to deionized water and stirred evenly. The mixture was then mechanically stirred at low speed at 400-800 rpm for 30-40 minutes to ensure uniform suspension of the microcapsules. The pH was adjusted to 6.5 with sodium hydroxide solution to obtain a long-lasting bactericidal suspension resistant to rain washout. The ratio of the dispersant SP-2206, thickener magnesium aluminum silicate, xanthan gum, antifreeze glycerol, preservative Kathon, surfactant SP-4026SJ, sustained-release microcapsule powder, and deionized water is 12-15g: 3-5g: 1-2g: 15-18g: 1-1.5g: 3-3.4g: 520-530g: 400-460mL.

10. A rainfast long-acting bactericidal suspension characterized in that, It is prepared by the method for preparing a long-lasting bactericidal suspension resistant to rain washout as described in any one of claims 1-9.

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