Compound nanogel sustained-release preparation, preparation method and application thereof

Abstract

This invention relates to the field of agricultural pest control, and particularly to a compound nanogel sustained-release agent, its preparation method, and its application. This invention provides a compound nanogel sustained-release agent comprising bromonitol, a synergist, a carrier material, and a cross-linking agent, wherein the synergist includes one or more of kasugamycin, amino oligosaccharides, thiazolium zinc, and copper hydroxide. This invention prepares a nanogel sustained-release agent by compounding bromonitol and the synergist, which has significant preventive effects against plant bacterial diseases such as bacterial wilt, bacterial angular leaf spot, canker, and soft rot. Furthermore, the compound nanogel sustained-release agent of this invention has small particle size, stable physicochemical properties under cold and heat, good dispersibility in water, no particle agglomeration, no particle size increase, a decomposition rate of less than 5%, a long-lasting effect, good safety, is not prone to inducing drug resistance, requires a small dosage, and simultaneously increases yield and efficiency.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of agricultural prevention and treatment, in particular to a compound nanogel slow-release agent and a preparation method and application thereof. BACKGROUND

[0002] Bacterial disease is a disease caused by bacterial infection of plants. In recent years, it has been very serious, such as tomato bacterial wilt, ginger bacterial wilt, Chinese cabbage soft rot, cucumber bacterial angular spot, rice bacterial leaf blight, corn stem rot, wheat black leg disease, citrus canker and the like. At present, the main prevention and treatment method in China is pesticide prevention and treatment, but there are few effective prevention and treatment agents, and at the same time, the bacterial resistance is increasing year by year due to long-term use of the same agent, thereby leading to short effective period and poor drug efficacy; it can be seen that the difficulty of chemical prevention and treatment is increasing; and due to excessive use of pesticides, environmental pollution and increase of farmers' drug cost are caused, which is not conducive to the sustainable development of agriculture. SUMMARY

[0003] In order to solve the above problems, the present application provides a compound nanogel slow-release agent and a preparation method and application thereof. The present application fully utilizes the potential use of nanotechnology in the protection and delivery of drugs by preparing a nano-pesticide preparation, and provides a new driving force for sustainable agricultural development; and the compound nanogel slow-release agent can effectively prevent and treat bacterial diseases, and has the advantages of long effective period, good drug efficacy, low cost and no environmental pollution.

[0004] In order to achieve the above purpose, the present application provides the following technical scheme:

[0005] The present application provides a compound nanogel slow-release agent, which comprises the following raw materials in mass percentage: 1-70% of effective ingredient, 0.5-90% of carrier material, 0.1-20% of crosslinking agent and 0.1-10% of surfactant; the effective ingredient comprises bromonitromethanol and synergist; the synergist comprises one or more of mycostatin, amino oligosaccharide, zinc thiazole and copper hydroxide; and the mass ratio of bromonitromethanol to synergist is (1-80):(1-80).

[0006] Preferably, the following raw materials in mass percentage are included: 1-50% of effective ingredient, 25-85% of carrier material, 1-17% of crosslinking agent and 0.2-10% of surfactant.

[0007] Preferably, the mass ratio of bromonitromethanol to synergist is (1-40):(1-40).

[0008] Preferably, the mass ratio of bromonitromethanol to synergist is (1-20):(1-20).

[0009] Preferably, the surfactant comprises a water-soluble surfactant; the water-soluble surfactant comprises one or a mixture of several of polycarboxylate, quaternary ammonium salt, polyoxyethylene ether phosphate, styryl phenol polyoxyethylene ether phosphate, sulfonate, polyvinyl alcohol, carboxylate and polyoxyethylene polyoxypropylene block copolymer; the carrier material comprises sodium alginate; the cross-linking agent comprises anhydrous copper sulfate.

[0010] The application provides a preparation method of the above-mentioned complex nano-gel sustained-release agent, comprising the following steps:

[0011] The bromonitromethanol, the synergist, the carrier material and the surfactant are mixed with water to obtain a first mixed solution; the first mixed solution is added to an oil phase under high-speed shearing to obtain a second mixed solution; the mass ratio of the oil phase to the first mixed solution is (1.5-20):1; the cross-linking agent is added dropwise to the second mixed solution to obtain the complex nano-gel sustained-release agent.

[0012] Preferably, the oil phase comprises one or several of cyclohexane, isopropyl alcohol, rapeseed oil, dimethylbenzene, methyl oleate, 200# solvent oil and methyl esterified soybean oil.

[0013] Preferably, the dropping speed is 30-60 drops / min.

[0014] The application provides an application of the above-mentioned complex nano-gel sustained-release agent or the complex nano-gel sustained-release agent prepared by the above-mentioned preparation method in preventing and treating plant bacterial diseases.

[0015] Preferably, the bacterial diseases comprise bacterial wilt, angular leaf spot, brown spot, basal rot, bacterial canker, soft rot, stem rot and bacterial leaf blight.

[0016] The application provides a method for preventing and treating plant bacterial diseases, the method comprising spraying, drip irrigation, root irrigation, spreading, hole application or seed dressing the above-mentioned complex nano-gel sustained-release agent or the sustained-release agent prepared by the above-mentioned preparation method.

[0017] Beneficial effects: the application provides a complex nanogel sustained-release agent containing bromonitril, synergist, carrier material and crosslinking agent, wherein the synergist includes one or more of mycobacillin, amino oligosaccharide, zinc thiazole and copper hydroxide, and the mass ratio of bromonitril and synergist is (1-80):(1-80). The application prepares the nanogel sustained-release agent by compounding bromonitril and synergist, which has a significant prevention effect on plant bacterial diseases such as plant bacterial wilt, bacterial angular spot, bacterial wilt and soft rot, and the complex nanogel sustained-release agent has the advantages of small particle size, stable physical and chemical properties in cold and hot storage (0℃, 7d; 54℃, 14d), good water dispersion, no particle adhesion, no particle size growth, a decomposition rate of less than 5%, a long effective period, good safety, less drug resistance, good suspension stability, good drug efficacy and convenient use, and can also delay drug resistance and increase yield and efficacy.

[0018] Moreover, the application provides a preparation method of the complex nanogel sustained-release agent, and the preparation method has the advantages of simple process, energy saving, no pollution, less harm to the environment, and good application prospect. DETAILED DESCRIPTION

[0019] Unless otherwise specified, the substances in the application are obtained by conventional purchase by those skilled in the art.

[0020] The application provides a complex nanogel sustained-release agent, which contains the following raw materials in mass percentage: 1-70% of effective components, 0.5-90% of carrier materials, 0.1-20% of crosslinking agents and 0.1-10% of surfactants; the effective components include bromonitril and synergist; the synergist includes one or more of mycobacillin, amino oligosaccharide, zinc thiazole and copper hydroxide; and the mass ratio of bromonitril and synergist is (1-80):(1-80).

[0021] Preferably, the raw materials of the complex nanogel sustained-release agent contain the following raw materials in mass percentage: 1-50% of effective components, 25-85% of carrier materials, 1-17% of crosslinking agents and 0.2-10% of surfactants; more preferably, the raw materials contain 15-30% of effective components, 55-70% of carrier materials, 5-10% of crosslinking agents and 5-10% of surfactants.

[0022] Preferably, the mass ratio of bromonitril and synergist is (1-40):(1-40), more preferably (1-20):(1-20), and most preferably (1-4):(1-2).

[0023] In the present application, the surface active agent preferably comprises a water-soluble surface active agent; the water-soluble surface active agent preferably comprises a mixture of one or several of polycarboxylate, quaternary ammonium salt, polyoxyethylene ether phosphate, styryl phenol polyoxyethylene ether phosphate, sulfonate, polyvinyl alcohol, carboxylate and polyoxyethylene polyoxypropylene block copolymer; the sulfonate preferably comprises sodium dodecyl sulfonate; the quaternary ammonium salt comprises dodecyl trimethyl ammonium bromide; the polyoxyethylene polyoxypropylene block copolymer preferably comprises an EO-PO block copolymer; the carboxylate is preferably sodium polyacrylate; the carrier material preferably comprises sodium alginate; and the cross-linking agent preferably comprises anhydrous copper sulfate.

[0024] The bromonitromethanol is used in combination with the meson, the amino oligosaccharide, the zinc thiazole and / or the copper hydroxide to achieve the effect of preventing and treating bacteria; the sodium alginate is a carrier material for preparing the compound nanogel sustained-release agent, which can increase the sustained-release effect of the medicament; the surface active agent can play a role in dispersing the effective components in the preparation process; the copper sulfate is used as a cross-linking agent, and the copper ions and the uniformly dispersed sodium alginate are cross-linked to form a three-dimensional network gel, and the copper ion content in the compound nanogel sustained-release agent is increased, thereby increasing the sustained-release effect of the medicament; the copper ions are slowly released after the compound nanogel sustained-release agent is applied, and have the effect of killing bacteria and further improving the efficacy.

[0025] The present application provides a preparation method of the compound nanogel sustained-release agent, which comprises the following steps:

[0026] The bromonitromethanol, the synergist, the carrier material and the surface active agent are mixed with water to obtain a first mixed solution; the first mixed solution is added to an oil phase under high-speed shearing to obtain a second mixed solution; the mass ratio of the oil phase to the first mixed solution is (1.5-20):1; and the cross-linking agent is added dropwise to the second mixed solution to obtain the compound nanogel sustained-release agent.

[0027] The present application provides a preparation method of the compound nanogel sustained-release agent, which comprises the following steps:

[0028] In the present application, when the synergist preferably comprises mesoformin and / or amino oligosaccharide, the mass ratio of bromonitromethanol, synergist, carrier material, surfactant and water is preferably (1-30):(0.1-20):(10-200):(1-10):(100-1000), more preferably (1-16):(0.5-10):(10-90):(2-5):(100-500); the water is preferably distilled water. The present application does not have any limitation on the mixing method, which can be performed by using methods well known to those skilled in the art.

[0029] The present application first dissolves bromonitromethanol, water-soluble mesoformin and / or amino oligosaccharide, carrier material and surfactant in water as a first mixed solution, adds the first mixed solution into an oil phase for high-speed shearing to prepare a second mixed solution, then adds a crosslinking agent solution into the second mixed solution, stirs uniformly, and then ultrasonicates to disperse into nanoparticles, and uses the crosslinking agent to form a three-dimensional network gel with the carrier material in the second mixed solution by crosslinking to wrap the effective components therein.

[0030] The shearing rate of the present application is preferably 8000-20000 rpm, more preferably 8000-19000 rpm; the shearing time is preferably 1-5 min, more preferably 1-4 min; and the shearing temperature is preferably 5-50°C, more preferably 20-35°C.

[0031] In the present application, the oil phase preferably comprises one or more of cyclohexane, isopropyl alcohol, rapeseed oil, dimethylbenzene, methyl oleate, 200# solvent oil and methyl esterified soybean oil.

[0032] In the present application, the concentration of the crosslinking agent is preferably 0.5-3 m / L, more preferably 1.5 m / L.

[0033] The present application further comprises ultrasonic dispersion, centrifugation and drying after the cross-linking agent is added dropwise to the second mixed solution, to obtain the compounded nanogel sustained-release agent. The speed of adding dropwise is preferably 30-60 drops / min, more preferably 30-50 drops / min. The dispersion mode is preferably ultrasonic dispersion, the ultrasonic dispersion time is preferably 0.5-2 h, more preferably 0.5-1.6 h, and most preferably 0.5-1.3 h. The centrifugation is preferably performed 3 times to obtain a compounded nanogel sustained-release agent with higher purity. The centrifugation speed is preferably 10,000 rpm, and the centrifugation time is preferably 10 min. After each centrifugation, the centrifugation precipitate is preferably washed with an equal amount of isopropyl alcohol. The drying time is preferably 24 h, and the drying temperature is preferably 25°C. The ultrasonic time is preferably 0.5-3 h, more preferably 0.5-2 h. The ultrasonic frequency is preferably 15-25 kHz, more preferably 20-25 kHz. In the present application, the oil phase and the solvent (water) of the first mixed solution are all discarded by centrifugation and drying, so that the prepared compounded nanogel sustained-release agent product does not include the solvent of the first mixed solution and the oil phase.

[0034] In the present application, when the synergist preferably comprises zinc thiazole and / or copper hydroxide, the present application preferably mixes bromonitromethanol, a synergist, a surfactant and a carrier material with water to obtain a first mixed solution (dispersed phase). The first mixed solution is added to an oil phase under high-speed shearing conditions to obtain a second mixed solution. A cross-linking agent is added dropwise to the second mixed solution (W / O type multi-phase dispersion liquid) to obtain a compounded nanogel sustained-release agent.

[0035] In the present application, after bromonitromethanol, a synergist, a surfactant, a carrier and water are uniformly mixed to obtain a first mixed solution, the first mixed solution is added to an oil phase to prepare a second mixed solution by high-speed shearing, and then a cross-linking agent is added to prepare a nanogel sustained-release agent. This method is simple, energy-saving, pollution-free, and has good application prospects.

[0036] In the present application, the mass ratio of bromonitromethanol, a synergist, a carrier material, a surfactant and water is preferably (1-30):(0.1-20):(10-200):(1-10):(100-1000), more preferably (1-16):(0.5-10):(10-90):(2-5):(100-500). The water is preferably distilled water. The mixing mode is not limited in the present application, and any method known to those skilled in the art can be used.

[0037] The bromonitromethanol, synergist, surfactant and carrier material are mixed with water, and then wet grinding and filtering are preferably performed on the mixed solution; in the present application, the wet grinding is preferably performed in a grinding cylinder; the wet grinding is preferably in a circulation mode; the mass ratio of grinding beads to the mixed solution is (1-3):1, more preferably 2:1; the grinding beads are preferably zirconium beads; the particle size of the zirconium beads is preferably 1.8 mm; the rotation speed of the wet grinding is preferably 2000-25000 rpm, more preferably 3000-23000 rpm, further preferably 5000-20000 rpm, and most preferably 6000-19000 rpm; the wet grinding time is preferably 3-4 h, more preferably 3.2-3.8 h; the particle size of the obtained grinding solution after wet grinding is preferably <400 nm; the filtering is preferably performed using a 0.45 μm microporous filter membrane.

[0038] The rotation speed of the shearing is preferably 8000-20000 rpm, more preferably 8000-19000 rpm, and most preferably 15000 rpm; the shearing time is preferably 1-5 min, more preferably 2-4 min, and most preferably 3 min; the shearing temperature is preferably 5-50°C, and more preferably 20-35°C.

[0039] In the present application, the concentration of the crosslinking agent is preferably 0.5-3 m / L, and more preferably 1.5 m / L.

[0040] After the crosslinking agent is added dropwise to the second mixed solution, the obtained mixed solution is preferably subjected to ultrasonic treatment, centrifugation and drying to obtain a compounded nanogel sustained-release agent. The ultrasonic treatment is preferably ultrasonic dispersion; the ultrasonic treatment time is preferably 0.5-3 h, more preferably 1-2 h; the ultrasonic frequency is preferably 5-25 KHz, and more preferably 20-25 KHz; the centrifugation is preferably performed 3 times to obtain a compounded nanogel sustained-release agent with higher purity; the centrifugation rotation speed is preferably 10000 rpm; the centrifugation time is preferably 10 min; the centrifugation precipitate is preferably washed with an equal amount of isopropyl alcohol after each centrifugation; the drying time is preferably 24 h; and the drying temperature is preferably 25°C. In the present application, the oil phase and the solvent of the first mixed solution are discarded through centrifugation and drying, and therefore the prepared compounded nanogel sustained-release agent product does not include the water and oil phase in the first mixed solution.

[0041] The compound nanogel sustained-release agent of the present application is prepared by wrapping, coupling, inlaying and other ways of pesticide with high molecular nanomaterials, fully utilizes the potential use of nanotechnology in drug protection and delivery, provides a new power for sustainable agricultural development, and can effectively prevent and control bacterial diseases; therefore, the compound nanogel sustained-release agent of the present application can be used for preventing and controlling plant bacterial diseases.

[0042] The present application provides the application of the above-mentioned compound nanogel sustained-release agent or the sustained-release agent prepared by the above-mentioned preparation method in preventing and controlling plant bacterial diseases. In the present application, the bacterial diseases preferably include bacterial wilt, angular leaf spot, brown spot, basal rot, bacterial wilt, soft rot, stem rot and bacterial leaf blight; and the plants preferably include ginger, Chinese cabbage, rice, citrus, cotton, strawberry, potato, soybean, eggplant, tomato, wheat, tobacco, cucumber, konjac, gourd, corn and rice, etc. The effect of the compound nanogel sustained-release agent is verified by virulence test and field test, and the results show that the compound nanogel sustained-release agent of the present application has a longer effective period than the commercially available single agent and the compound nanogel sustained-release agent prepared by using calcium chloride as a crosslinking agent, reaches more than 90 days, is safe to crops, reduces the amount of pesticide, and reduces the cost.

[0043] The present application provides a method for preventing and controlling plant bacterial diseases, which comprises spraying, drip irrigation, root irrigation, spreading, hole application or seed dressing the above-mentioned compound nanogel sustained-release agent or the sustained-release agent prepared by the above-mentioned preparation method; and the application amount of the method is preferably 2-50 g a.i. / mu, and more preferably 15-50 g a.i. / mu.

[0044] In order to further illustrate the present application, the compound nanogel sustained-release agent, the preparation method and the application thereof provided by the present application are described in detail below with reference to the examples, but they should not be understood as limiting the scope of protection of the present application.

[0045] Example 1

[0046] The raw materials of the compound nanogel sustained-release agent (1.2% bronopol·mesna compound nanogel sustained-release agent) are shown in Table 1, wherein the mass ratio of bronopol to mesna is 2:1.

[0047] Table 1 Components of 1.2% bronopol·mesna compound nanogel sustained-release agent

[0048] Components Dosage Bronopol (as active ingredient) 0.1g Mycosubtilin (as active ingredient) 0.05g Sodium alginate (carrier material) 9g Anhydrous copper sulfate (cross-linking agent) 1g Sodium dodecylsulfonate (sulfonate surfactant) 0.5g Methyl oleate (oil phase) 90g Distilled water (solvent for first mixed solution) 30g

[0049] a. Respectively take bromonitromethanol, myclosin, sodium alginate, sodium dodecyl sulfonate into distilled water and stir to be uniform as the first mixed solution, wherein the mass ratio of bromonitromethanol, myclosin, sodium alginate, sodium dodecyl sulfonate and distilled water is 0.1:0.05:9:0.5:30, i.e. 1:0.5:90:5:300;

[0050] b. At 20℃, under high-speed shearing at 8000rpm, slowly drop the first mixed solution prepared in step (a) into methyl oleate to obtain W / O microemulsion (second mixed solution) under shearing for 1min; the mass ratio of oil phase and the first mixed solution is 18:7.93, i.e. 2.2:1;

[0051] c. Prepare copper sulfate aqueous solution by adding water to anhydrous copper sulfate, with a concentration of 1.5m / L, and drop it into the W / O microemulsion in step (b) at a drop rate of 30 drops / min, stir uniformly and then ultrasonic for 0.5h at a frequency of 20KHz to form a uniformly dispersed nanosuspension.

[0052] d. Place the nanosuspension in step (c) in a high-speed centrifuge and centrifuge at 10000rpm for 10min, discard the supernatant, add an equal amount of isopropanol to wash the centrifugal precipitate, centrifuge again at 10000rpm for 10min, repeat the operation for three times, and then vacuum dry the centrifugal precipitate at 25℃ for 24h to obtain the prepared nanogel sustained-release agent, i.e. 1.2% bromonitromethanol·myclosin compound nanogel sustained-release agent.

[0053] Through the above step (d), all the oil phase and the first mixed solution solvent in the formula have been discarded, so the prepared bromonitromethanol nanogel sustained-release agent product does not include the first mixed solution solvent and the oil phase.

[0054] The particle size, surface Zate potential and particle dispersion coefficient of the 1.2% bromonitromethanol·myclosin compound nanogel sustained-release agent prepared in this embodiment were determined: 10mg of the above prepared nanogel sustained-release agent was added into 100mL anhydrous ethanol, and ultrasonic was applied until the sample was completely dispersed, and then a laser particle size analyzer (LPA) (ZS90, Malvern Company, UK) was used for determination;

[0055] Drug loading determination: 0.1g of the sample was dispersed in 10mL of 0.1M sodium citrate solution, and after it was completely dissolved, the bromonitromethanol and myclosin contents were determined by high performance liquid chromatography;

[0056] Thermal storage stability determination: thermal storage stability determination was carried out according to GB / T19136-2003;

[0057] Low temperature stability determination: low temperature stability determination was carried out according to GB / T19137;

[0058] Sedimentation Rate (F) was calculated by the following method: the above suspension was placed in a measuring cylinder, mixed well, and the total volume V0 of the suspension was measured. After 10 weeks, the volume Vu of the sediment was measured when the sedimentation surface was no longer changing. The sedimentation rate F was calculated as follows: F = Vu / V0 x 100%.

[0059] The results are shown in Table 2.

[0060] Table 2 Quality and technical indexes of 1.2% bronopol · mesnagin complex nanogel sustained-release preparation

[0061] Test item / test method Test result Total active ingredient content (%) Bronopol: 0.83; mycosubtilin: 0.42 Average particle size (nm) 96 Surface Zate potential (mV) -20.5 Particle dispersion coefficient 0.065 Sedimentation volume ratio 0.99 Low-temperature stability Pass Thermal storage stability Pass, disintegration rate < 5%

[0062] As shown in Table 2, the complex nanogel sustained-release preparation of the present embodiment has small particle size, good dispersity, and stable physicochemical properties.

[0063] Example 2

[0064] The raw materials of the complex nanogel sustained-release preparation (25% bronopol · amino oligosaccharide complex nanogel sustained-release preparation) are shown in Table 3, wherein the mass ratio of bronopol to amino oligosaccharide is 4:1.

[0065] Table 3 Components of 25% bronopol · amino oligosaccharide complex nanogel sustained-release preparation

[0066]

[0067]

[0068] Preparation was carried out according to the preparation method of Example 1, wherein the emulsification shear rate was 10000 rpm, the emulsification time was 2 min, ultrasonic treatment was performed for 1 h, and the other operations were the same as in Example 1. The ratio of the oil phase to the first mixed solution was 150:56.8, i.e. 2.641:1.

[0069] The oil phase and the first mixed solution solvent in the formula have been completely discarded through step (d) above, and therefore the finished bronopol nanogel sustained-release preparation does not include the first mixed solution solvent and the oil phase.

[0070] Each index was detected according to the method described in Example 1, and the quality and technical indexes of the 25% bronopol · amino oligosaccharide nanogel sustained-release preparation prepared in Example 2 are shown in Table 4.

[0071] Table 4 Quality and technical indexes of 25% bronopol · amino oligosaccharide nanogel sustained-release preparation

[0072] Test item / test method Test result Total active ingredient content (%) Bronopol: 5.04; amino-oligosaccharide: 20.16 Average particle size (nm) 90 Surface Zate potential (mV) -22.5 Particle dispersion coefficient 0.074 Sedimentation volume ratio 0.98 Low-temperature stability Pass Thermal storage stability Pass, disintegration rate < 5%

[0073] As shown in Table 4, the complex nanogel sustained-release preparation of the present application has small particle size, good dispersity and stable physicochemical properties.

[0074] Example 3

[0075] The raw materials of the complex nanogel sustained-release preparation (44% bronopol·zinc thiazole complex nanogel sustained-release preparation) are shown in Table 5, wherein the mass ratio of bronopol to zinc thiazole is 1:1.

[0076] Table 5 Components of 44% bronopol·zinc thiazole complex nanogel sustained-release preparation

[0077]

[0078]

[0079] a. Bronopol, zinc thiazole, sodium alginate, sodium polyacrylate and polyvinyl alcohol were weighed and added into distilled water, respectively, and stirred until uniform. Then, the mixture was transferred into a grinding cylinder and wet ground by using a grinder (grinding beads: zirconium beads, mass ratio of grinding beads to the obtained mixture solution: 2:1; particle size: 1.8 mm; rotation speed: 10000 rpm; grinding mode: circulating grinding, grinding for 3 h, and then filtered by using a 0.45 μm microporous filter. The filtrate was taken as the dispersion phase (first mixed solution), wherein the mass ratio of bronopol, zinc thiazole, sodium alginate, sodium polyacrylate, polyvinyl alcohol and distilled water was 0.7:0.7:1:0.15:0.15:30, i.e. 7:7:10:1.5:1.5:300.

[0080] b. The dispersion phase prepared in step (a) was slowly added into a mixture of xylene and 200# solvent oil under high-speed shearing at 25°C and 15000 rpm for 3 min to obtain a W / O type multi-phase dispersion liquid (second mixed solution), wherein the mass ratio of oil phase to dispersion phase (first mixed solution) was 30:12.7, i.e. 2.36:1.

[0081] c. Anhydrous copper sulfate was added into water to prepare a copper sulfate aqueous solution with a concentration of 1.5 m / L, which was added dropwise into the W / O type multi-phase dispersion liquid (second mixed solution) prepared in step (b) at a dropping speed of 60 drops / min. After stirring, the mixture was ultrasonically treated for 1.5 h at an ultrasonic frequency of 25 KHz to form a uniformly dispersed nanosuspension.

[0082] d. The nanosuspension in step (c) is placed in a high-speed centrifuge and centrifuged at 10,000 rpm for 10 min, the supernatant is discarded, and the same amount of isopropanol is added to wash the centrifugal precipitate, which is centrifuged again at 10,000 rpm for 10 min, and the operation is repeated three times. Then, the centrifugal precipitate is vacuum dried at 25°C for 24 h to obtain the 44% bromonitromethanol·zinc thiazole nanogel sustained-release preparation.

[0083] The oil phase and the solvent of the dispersed phase (the first mixed solution) in the formula have been completely discarded through the above step (d), and therefore the finished bromonitromethanol nanogel sustained-release preparation prepared does not include the solvent of the dispersed phase (the first mixed solution) and the oil phase.

[0084] The indicators are detected according to the method described in Example 1, and the quality technical indicators of the 44% bromonitromethanol·zinc thiazole nanogel sustained-release preparation prepared in Example 3 are shown in Table 6.

[0085] Table 6 Quality technical indicators of the 44% bromonitromethanol·zinc thiazole complex nanogel sustained-release preparation

[0086] Test item / test method Test result Total active ingredient content (%) Bronopol: 22.05; thiazolyl zinc: 22.05 Average particle size (nm) 356 Surface Zate potential (mV) -19.0 Particle dispersion coefficient 0.113 Sedimentation volume ratio 0.99 Low-temperature stability Pass Thermal storage stability Pass, disintegration rate < 5%

[0087] As can be seen from the experimental data in Table 6, the nanogel sustained-release preparation with small particles, good dispersity, and stable physicochemical properties can be obtained in this example.

[0088] Example 4

[0089] 39% bromonitromethanol·copper hydroxide complex nanogel sustained-release preparation

[0090] The raw materials of the complex nanogel sustained-release preparation (the 39% bromonitromethanol·copper hydroxide complex nanogel sustained-release preparation) are shown in Table 7, wherein the mass ratio of bromonitromethanol to copper hydroxide is 1.5:1.

[0091] Table 7 Components of the 39% bromonitromethanol·copper hydroxide complex nanogel sustained-release preparation

[0092]

[0093] Preparation is carried out according to the preparation method of Example 3, wherein the wet grinding time is 4 h, the emulsification shearing rate is 20,000 rpm, emulsification is carried out for 5 min, ultrasonic is carried out for 2 h, and other operations are the same as in Example 3, wherein the ratio of the oil phase to the first mixed solution is 130:25.2, i.e. 5.16:1.

[0094] The oil phase and the solvent of the first mixed solution in the formula have been completely discarded through the above step (d), and therefore the finished bromonitromethanol nanogel sustained-release preparation prepared does not include the solvent of the first mixed solution and the oil phase.

[0095] The indicators were detected according to the method described in Example 1. The quality technical indicators of the 39% bromonitromethanol·copper hydroxide nanogel sustained-release preparation prepared in Example 4 are shown in Table 8.

[0096] Table 8 Quality technical indicators of the 39% bromonitromethanol·copper hydroxide nanogel sustained-release preparation

[0097] Test item / test method Test result Total active ingredient content (%) Bronopol: 23.22; copper hydroxide: 15.48 Average particle size (nm) 234 Surface Zate potential (mV) -22.5 Particle dispersion coefficient 0.074 Sedimentation volume ratio 0.98 Low-temperature stability Pass Thermal storage stability Test item / test method Test result Total active ingredient content (%) Bronopol: 23.22; copper hydroxide: 15.48 Average particle size (nm) Surface Zate potential (mV) Particle dispersion coefficient Sedimentation volume ratio Low-temperature stability Pass Thermal storage stability Test item / test method Test result Total active ingredient content (%) Pass, disintegration rate < 5%

[0098] As can be seen from the experimental data described in Table 8, the complex nanogel sustained-release preparation of the present embodiment can be obtained, which has small particles, good dispersity, and stable physicochemical properties.

[0099] Application Example 1

[0100] The toxicity and synergistic effect of the complex nanogel sustained-release preparation were determined by a method combining indoor toxicity determination and field test.

[0101] First, the synergistic ratio (SR) of the two agents after being compounded in a certain proportion was determined by indoor toxicity determination. SR<0.5 indicates antagonistic effect, 0.5≤SR≤1.5 indicates additive effect, and SR>1.5 indicates synergistic effect. On this basis, field test was further conducted.

[0102] Method for indoor toxicity determination: according to the experimental design concentration, a certain amount of drug solution was added to cooled NB medium, 4 replicates were set for each treatment, the bacteria grown on NA medium were diluted with sterile water to 1×10 7 spores / mL concentration suspension, 100 uL of bacterial solution was inoculated into each treatment medium, and was placed in a 28-30℃ condition for shaking (120 r / min).

[0103] The turbidity of each treatment was determined before the start of the culture, and the turbidity of each treatment was determined and recorded when the control treatment reached the logarithmic growth phase. According to the investigation data, the bacterial growth inhibition rate was calculated according to formula II.

[0104] Formula II, wherein P is the growth inhibition rate, A0is the turbidity increase value of the blank control, and A1is the turbidity increase value of the agent treatment.

[0105] The logarithmic values of the agent concentrations and the probability values of the control effects were subjected to regression analysis by SPSS, and the EC 50 values of each treatment were calculated, and the EC 50 values of each agent were calculated. At the same time, the synergistic ratio (SR) of the two agents in different proportions was calculated according to the Wadley method. SR<0.5 indicates antagonistic effect, 0.5≤SR≤1.5 indicates additive effect, and SR>1.5 indicates synergistic effect. The calculation formulas are as follows: SR=EC 50 (theoretical value) / EC 50 (observed value), formula III, EC50 Theoretical value) = (a + b) / [(a / EC 50 of A) + (b / EC 50 of B)], Formula IV, wherein: a and b are the proportions of active ingredients A and B in the combination, A is bronopol, and B is selected from one of the group consisting of mycostatin, oligosaccharide amino, zinc thiazole, and copper hydroxide.

[0106] 1.1, Test pathogen: tomato Pseudomonas solanacearum (Pseudomonas solanacearum SHBCC D10937, Shanghai Baocang Biotechnology Center); test design: effective inhibition concentration ranges of bronopol and hexaconazole technical and different mixtures thereof were determined through preliminary tests. The results of the virulence determination are shown in Table 9.

[0107] Table 9 Analysis of the results of the virulence determination of the bronopol and mycostatin complex nanogel sustained-release agent on tomato Pseudomonas solanacearum

[0108]

[0109] As can be seen from Table 9, the synergistic ratio SR of bronopol and mycostatin in the ratio of (1:80) to (80:1) on tomato Pseudomonas solanacearum is greater than 1.5, indicating that the two exhibit synergistic effects in the ratio of (1:80) to (80:1). When the ratio of bronopol and mycostatin is (1:10) to (10:1), the synergistic effect is more prominent, with the synergistic ratio being greater than 2.0. In particular, when the ratio of bronopol and mycostatin is 4:1, the synergistic ratio is the largest, and the synergistic effect is the most obvious.

[0110] 1.2, Test pathogen: carrot Erwinia carotovora (Erwinia carotovora SHBCC D72647, Shanghai Baocang Biotechnology Center); test design: effective inhibition concentration ranges of bronopol and oligosaccharide amino technical and different mixtures thereof were determined through preliminary tests. The results of the virulence determination are shown in Table 10.

[0111] Table 10 Analysis of the results of the virulence determination of the bronopol and oligosaccharide amino complex on Erwinia carotovora

[0112]

[0113] As can be seen from Table 10, the synergistic ratio SR of bronopol and oligosaccharide amino in the ratio of (1:80) to (80:1) on Erwinia carotovora is greater than 1.5, indicating that the two exhibit synergistic effects in the ratio of (1:80) to (80:1). When the ratio of bronopol and oligosaccharide amino is (1:40) to (20:1), the synergistic effect is more prominent, with the synergistic ratio being greater than 2.13. In particular, when the ratio of bronopol and oligosaccharide amino is 1:2, the synergistic ratio is the largest, and the synergistic effect is the most obvious.

[0114] 1.3, Test pathogenic bacteria: Pseudomonas solanacearum (Pseudomonas solanacearum SHBCC D10937, Shanghai Baocang Biotechnology Center); Test design: The effective inhibition concentration range of bromonitril and zineb and their different ratio mixtures was determined through preliminary test. The toxicity determination results are shown in Table 11.

[0115] Table 11 Analysis of toxicity determination results of bromonitril and zineb complex on Pseudomonas solanacearum

[0116]

[0117]

[0118] From Table 11, it can be seen that when the ratio of bromonitril and zineb is (1:80)~(80:1), the synergistic ratio SR of Pseudomonas solanacearum is greater than 1.5, which shows that the two mixed in the range of (1:80)~(80:1) all show synergistic effect. When the ratio of bromonitril and amino oligosaccharide is (1:40)~(30:1), the synergistic effect is more prominent, and the synergistic ratio is all above 2.04. Especially, when the ratio of bromonitril and meson is 1:1, the synergistic ratio is the largest, and the synergistic effect is the most obvious.

[0119] 1.4, Test pathogenic bacteria: Erwinia carotovora (Erwinia carotovora SHBCC D72647, Shanghai Baocang Biotechnology Center); Test design: The effective inhibition concentration range of bromonitril and copper hydroxide and their different ratio mixtures was determined through preliminary test. The toxicity determination results are shown in Table 12.

[0120] Table 12 Analysis of toxicity determination results of bromonitril and copper hydroxide complex on Erwinia carotovora

[0121]

[0122]

[0123] From Table 12, it can be seen that when the ratio of bromonitril and copper hydroxide is (1:80)~(80:1), the synergistic ratio SR of Erwinia carotovora is greater than 1.5, which shows that the two mixed in the range of (1:80)~(80:1) all show synergistic effect. When the ratio of bromonitril and amino oligosaccharide is (1:40)~(40:1), the synergistic effect is more prominent, and the synergistic ratio is all above 2.12. Especially, when the ratio of bromonitril and meson is 3:2, the synergistic ratio is the largest, and the synergistic effect is the most obvious.

[0124] Application Example 2

[0125] 2.1, perennial tomato planting, tomato bacterial wilt disease serious plot, a total of 17 treatments, treatment 1 prepared by example 1 of the complex nanogel slow release agent, the dosage is 30g a.i. / acre; treatment 2 is prepared by example 1 of the complex nanogel slow release agent, the dosage is 15g a.i. / acre; treatment 3 is prepared by example 2 of the complex nanogel slow release agent, the dosage is 30g a.i. / acre; treatment 4 is prepared by example 2 of the complex nanogel slow release agent, the dosage is 15g a.i. / acre; treatment 5 is prepared by example 3 of the complex nanogel slow release agent, the dosage is 30g a.i. / acre; treatment 6 is prepared by example 3 of the complex nanogel slow release agent, the dosage is 15g a.i. / acre; treatment 7 is prepared by example 4 of the complex nanogel slow release agent, the dosage is 30g a.i. / acre; treatment 8 is prepared by example 4 of the complex nanogel slow release agent, the dosage is 15g a.i. / acre; treatment 9 is reference agent 1 (1.2% bromothalonil·zhongshengmycin complex nanogel slow release agent is prepared by replacing anhydrous copper sulfate with calcium chloride of the same mass, other components and preparation process are the same as example 1), the dosage is 30g a.i. / acre; treatment 10 is reference agent 1, the dosage is 15g a.i. / acre; treatment 11 is reference agent 2 (the amount of bromothalonil in example 1 is changed to 0.135g, the amount of zhongshengmycin is changed to 0.015g, other conditions remain unchanged), the dosage is 30g a.i. / acre; treatment 12 is reference agent 2, the dosage is 15g a.i. / acre; treatment 13 is 20% bromothalonil wettable powder on the market, the dosage is 30g a.i. / acre; treatment 14 is 3% zhongshengmycin wettable powder, the dosage is 30g a.i. / acre; treatment 15 is 5% aminosugar oligosaccharide aqueous agent, the dosage is 30g a.i. / acre; treatment 16 is 77% copper hydroxide wettable powder, the dosage is 30g a.i. / acre; treatment 17 is 1.2% bromothalonil·zhongshengmycin wettable powder prepared by using conventional preparation method and conventional adjuvant in the art (the ratio of effective ingredients is consistent with example 1), the specific method is to mix bromothalonil, zhongshengmycin, dispersing agent, wetting agent and filler uniformly in a mixing cylinder, wherein bromothalonil (calculated as effective ingredient) is 0.83%, zhongshengmycin (calculated as effective ingredient) is 0.42%, dispersing agent is alkyl benzene sulfonate, the amount is 5%, wetting agent is sodium dodecyl sulfate, the amount is 3%, filler is white carbon black, make up to 100%, then mix uniformly after being pulverized by airflow pulverizer, the dosage is 30g a.i. / acre.

[0126] Each treatment is repeated 4 times, arranged randomly, take samples regularly, investigate the control effect on tomato bacterial wilt at different periods, and measure the yield of tomatoes at harvest, the results are shown in table 13. All the above treatments are diluted by the same amount of water and applied by drip irrigation.

[0127] Table 13. Control efficacy of different component compounded nanogel sustained-release agents on tomato bacterial wilt

[0128]

[0129] As can be seen from the results of Table 13, the prepared compounded nanogel sustained-release agents of Examples 1-4 have significantly higher prevention effects on tomato bacterial wilt than the commercially available agents, 1.2% bronopol · zhongshengjinjin wettable powder and the reference agents at the same amount and low dosage, and show obvious synergistic effects, and still have relatively high prevention effects and more obvious yield-increasing effects 90 days after the treatment. No phytotoxicity occurs during the test, and the safety is good. It can be seen that the prepared compounded nanogel sustained-release agents have the advantages of less amount of drug, long effective period, yield-increasing and efficiency-increasing effects, thereby reducing the production cost and reducing the generation of drug resistance. In addition, compared with the reference agent 1, the nanogel sustained-release agent prepared by using anhydrous copper sulfate instead of the conventional calcium chloride can effectively improve the prevention effect and the tomato yield. As can be seen from the reference agent 2, when the ratio of bronopol to zhongshengjinjin is greater than 80:1, the drug efficacy and yield-increasing rate significantly decrease.

[0130] 2.2, perennially planting cucumber, and selecting the plot where cucumber bacterial angular spot is serious, 17 treatments were set, treatment 1 was the prepared complex nano-hydrogel slow-release agent of example 1, the dosage was 40 g a.i. / mu; treatment 2 was the prepared complex nano-hydrogel slow-release agent of example 1, the dosage was 20 g a.i. / mu; treatment 3 was the prepared complex nano-hydrogel slow-release agent of example 2, the dosage was 40 g a.i. / mu; treatment 4 was the prepared complex nano-hydrogel slow-release agent of example 2, the dosage was 20 g a.i. / mu; treatment 5 was the prepared complex nano-hydrogel slow-release agent of example 3, the dosage was 40 g a.i. / mu; treatment 6 was the prepared complex nano-hydrogel slow-release agent of example 3, the dosage was 20 g a.i. / mu; treatment 7 was the prepared complex nano-hydrogel slow-release agent of example 4, the dosage was 40 g a.i. / mu; treatment 8 was the prepared complex nano-hydrogel slow-release agent of example 4, the dosage was 20 g a.i. / mu; treatment 9 was the reference agent 1 (25% bronas · oligosaccharide complex nano-hydrogel slow-release agent was prepared by using the same amount of calcium chloride instead of anhydrous copper sulfate, other components and preparation process were the same as example 2), the dosage was 40 g a.i. / mu; treatment 10 was the reference agent 1, the dosage was 20 g a.i. / mu; treatment 11 was the reference agent 2 (the amount of bronas in example 2 was changed to 0.3 g, the amount of oligosaccharide was changed to 1.7 g, other conditions were unchanged), the dosage was 40 g a.i. / mu; treatment 12 was the reference agent 2, the dosage was 20 g a.i. / mu; treatment 13 was 20% bronas wettable powder on the market, the dosage was 40 g a.i. / mu; treatment 14 was 3% zhengengmycin wettable powder, the dosage was 40 g a.i. / mu; treatment 15 was 5% oligosaccharide aqueous agent, the dosage was 40 g a.i. / mu; treatment 16 was 77% copper hydroxide wettable powder, the dosage was 40 g a.i. / mu; treatment 17 was 25% bronas · oligosaccharide wettable powder (the ratio of active ingredients was consistent with example 2) prepared by using the conventional preparation method and conventional adjuvant in the art, the specific method was that bronas, oligosaccharide, dispersing agent, wetting agent, filler were mixed uniformly in a mixing cylinder, wherein bronas was 5.04%, oligosaccharide was 20.16%, dispersing agent was naphthalene formaldehyde condensate sodium salt, the amount was 3%, wetting agent was alkyl naphthalene sulfonate, the amount was 3%, filler was kaolin, the rest was supplemented, then it was mixed uniformly after being pulverized by an air flow pulverizer, the specific dosage was 40 g a.i. / mu. Each treatment was repeated 4 times, a random arrangement method was used, samples were taken regularly, the control effects on cucumber bacterial angular spot at different times were investigated, and the yield of cucumber at harvest was determined, the results were shown in table 14. All the above treatments were diluted by the same amount of water and applied by root irrigation.

[0131] Table 14. Efficacy test of the complex nanogel sustained-release agent of different components for preventing and treating cucumber bacterial angular leaf spot

[0132]

[0133] As shown in the experimental data in Table 14, the complex nanogel sustained-release agent of bromonitril prepared in Examples 1-4 has a significantly higher prevention effect on cucumber bacterial angular leaf spot than the commercially available agent, 25% bromonitril · Zhengengmycin soluble solution and the reference agent at the same amount and low dose, and shows obvious synergistic effect. The prevention effect is still high at 90 days after the drug, and the yield-increasing effect is more obvious. No phytotoxicity occurs during the test, and the safety is good. Therefore, the complex nanogel sustained-release agent prepared in the application has the advantages of less amount of drug, long effective period, yield-increasing and efficiency-increasing effects, thereby reducing the production cost and reducing the generation of drug resistance. In addition, compared with the reference agent 1, the nanogel sustained-release agent prepared by using anhydrous copper sulfate instead of the conventional calcium chloride can effectively improve the prevention effect and the yield of cucumber. As shown in the reference agent 2, when the ratio of bromonitril to amino oligosaccharide is less than 1:80, the drug efficacy and yield-increasing rate decrease significantly.

[0134] 2.3, perennial corn, corn stem rot serious plot, a total of 15 treatments, treatment 1 prepared by example 1 of the complex nanogel slow release agent, the dosage is 50g a.i. / acre; treatment 2 is prepared by example 1 of the complex nanogel slow release agent, the dosage is 25g a.i. / acre; treatment 3 is prepared by example 2 of the complex nanogel slow release agent, the dosage is 50g a.i. / acre; treatment 4 is prepared by example 2 of the complex nanogel slow release agent, the dosage is 25g a.i. / acre; treatment 5 is prepared by example 3 of the complex nanogel slow release agent, the dosage is 50g a.i. / acre; treatment 6 is prepared by example 3 of the complex nanogel slow release agent, the dosage is 25g a.i. / acre; treatment 7 is prepared by example 4 of the complex nanogel slow release agent, the dosage is 50g a.i. / acre; treatment 8 is prepared by example 4 of the complex nanogel slow release agent, the dosage is 25g a.i. / acre; treatment 9 is reference 1 (44% bromothalonil·amino oligosaccharide complex nanogel slow release agent prepared by replacing anhydrous copper sulfate with calcium chloride of the same mass, other components and preparation process are the same as example 3), the dosage is 50g a.i. / acre; treatment 10 is reference 1, the dosage is 25g a.i. / acre; treatment 11 is commercially available 20% bromothalonil wettable powder, the dosage is 50g a.i. / acre; treatment 12 is 3% zhengengmycin wettable powder, the dosage is 50g a.i. / acre; treatment 13 is 5% amino oligosaccharide aqueous agent, the dosage is 50g a.i. / acre; treatment 14 is 77% copper hydroxide wettable powder, the dosage is 50g a.i. / acre; treatment 15 is 44% bromothalonil·thiabendazole suspension concentrate prepared by using conventional preparation method and conventional adjuvant in the art (the effective ingredient ratio is consistent with example 3), the specific method is that dispersing agent, wetting agent, defoaming agent, thickening agent (may be added or not), antifreeze agent (may be added or not) are mixed uniformly by high speed shearing, bromothalonil 22.05%, thiabendazole 22.05%, dispersing agent is alkyl phenol polyoxyethylene ether, the amount is 5%, wetting agent is sodium dodecyl benzene sulfonate, the amount is 2%, silicone defoaming agent 0.2%, thickening agent gum arabic 1%, antifreeze agent propylene glycol 3%. After mixing uniformly, bromothalonil and thiabendazole are ball milled in a ball mill for 2-3 hours, so that the particle size is all below 5μm, the rest is supplemented with deionized water, the dosage is 50g a.i. / acre. Each treatment is repeated 4 times, adopts random arrangement, takes sample regularly, investigates the control effect on corn stem rot at different periods, and measures the corn yield at harvest, the results are shown in table 15. All the above treatments are diluted by the same amount of water and applied by spraying.

[0135] Table 15 complex nanogel slow release agent of different components for controlling corn stem rot

[0136]

[0137] As can be seen from the results of Table 15, the complex nano-hydrogel sustained-release agent prepared in Examples 1-4 has a significantly higher prevention effect on corn stem rot than the commercially available agent, 44% bronopol·zineb suspension concentrate and the reference agent at the same drug amount and low dosage, and shows obvious synergistic effect, and still maintains a high prevention effect at 90 days after the drug, and the yield-increasing effect is more obvious. No drug damage occurs during the test, and the safety is good; thus, it can be seen that the prepared bronopol complex nano-hydrogel sustained-release agent has a small drug amount, a long effective period, a yield-increasing and efficiency-increasing effect, thereby reducing the production cost and reducing the generation of drug resistance. In addition, compared with the reference agent 1, the nano-hydrogel sustained-release agent prepared by using anhydrous copper sulfate instead of the conventional calcium chloride can effectively improve the prevention effect and the corn yield.

[0138] 2.4, perennial rice planting, rice white leaf blight serious plot, a total of 15 treatments, treatment 1 prepared by example 1 of the complex nanogel slow release agent, the dosage is 45g a.i. / mu; Treatment 2 is prepared by example 1 of the complex nanogel slow release agent, the dosage is 22.5g a.i. / mu; Treatment 3 is prepared by example 2 of the complex nanogel slow release agent, the dosage is 45g a.i. / mu; Treatment 4 is prepared by example 2 of the complex nanogel slow release agent, the dosage is 22.5g a.i. / mu; Treatment 5 is prepared by example 3 of the complex nanogel slow release agent, the dosage is 45g a.i. / mu; Treatment 6 is prepared by example 3 of the complex nanogel slow release agent, the dosage is 22.5g a.i. / mu; Treatment 7 is prepared by example 4 of the complex nanogel slow release agent, the dosage is 45g a.i. / mu; Treatment 8 is prepared by example 4 of the complex nanogel slow release agent, the dosage is 22.5g a.i. / mu; Treatment 9 is the reference agent 1 (with the same amount of calcium chloride instead of anhydrous copper sulfate to prepare 39% bronopol·copper hydroxide complex nanogel slow release agent other components and preparation process is the same as example 4), the dosage is 45g a.i. / mu; Treatment 10 is the reference agent 1, the dosage is 22.5g a.i. / mu; Treatment 11 is the commercially available 20% bronopol wettable powder, the dosage is 45g a.i. / mu; Treatment 12 is 3% zhengengmycin wettable powder, the dosage is 45g a.i. / mu; Treatment 13 is 5% amino oligosaccharide aqueous agent, the dosage is 45g a.i. / mu; Treatment 14 is 77% copper hydroxide wettable powder, the dosage is 45g a.i. / mu; Treatment 15 is prepared by using the conventional preparation method and conventional adjuvant of the art 39% bronopol·copper hydroxide wettable powder (the same effective ingredient ratio as example 4), the specific method is to mix bronopol, copper hydroxide, dispersing agent, wetting agent, filler uniformly in the mixing cylinder, wherein bronopol is 23.22%, copper hydroxide is 15.48%, dispersing agent is sodium lignosulfonate, the amount is 6%, wetting agent is sodium lauryl sulfate, the amount is 4%, carrier is attapulgite, the rest is made up. After being crushed by airflow pulverizer, it is mixed uniformly and can be used, the dosage is 45g a.i. / mu. All the above treatments are diluted by the same amount of water and applied by root irrigation.

[0139] Each treatment is repeated 4 times, using random arrangement, sampling regularly, investigating the control effect of different periods on rice white leaf blight, and measuring the yield of rice at harvest, the results are shown in table 16.

[0140] Table 16 complex nanogel slow release agent of different components for preventing and treating rice white leaf blight

[0141]

[0142]

[0143] As can be seen from the results of Table 16, the prepared complex nanogel sustained-release agent of Examples 1-4 has a significantly higher prevention effect on rice bacterial leaf blight than the commercially available 39% bronopol · copper hydroxide wettable powder and the reference agent at the same drug amount and low dosage, and shows obvious synergistic effect, and still maintains a high prevention effect 90 days after the drug, and the yield-increasing effect is more obvious. No phytotoxicity occurs during the test, and the safety is good; thus, the prepared complex nanogel sustained-release agent has the advantages of less drug amount, long effective period, yield-increasing and efficiency-increasing effects, thereby reducing the production cost and reducing the generation of drug resistance. In addition, compared with the reference agent, the nanogel sustained-release agent prepared by using anhydrous copper sulfate instead of the conventional calcium chloride can effectively improve the prevention effect and the yield of rice.

[0144] Although the present application has been disclosed with reference to the preferred embodiments, it is not intended to limit the present application, and any person skilled in the art can make various modifications and modifications without departing from the spirit and scope of the present application, and thus the protection scope of the present application should be defined by the claims.

Claims

1. A complex nanogel sustained release agent, characterized in that, The raw materials include the following mass percentages: 1-70% of an effective component, 0.5-90% of a carrier material, 0.1-20% of a crosslinking agent, and 0.1-10% of a surfactant; the effective component is bromonitromethanol and a synergist; the synergist is an aminosaccharide; and the mass ratio of the bromonitromethanol to the synergist is 1:2; The surfactant is a water-soluble surfactant; the water-soluble surfactant is a mixture of one or more of polycarboxylate, quaternary ammonium salt, polyoxyethylene ether phosphate, styryl phenol polyoxyethylene ether phosphate, sulfonate, polyvinyl alcohol, carboxylate, and polyoxyethylene polyoxypropylene block copolymer; the carrier material is sodium alginate; and the crosslinking agent is anhydrous copper sulfate. The preparation method of the complex nanogel sustained-release agent is as follows: The bromonitromethanol, the synergist, the carrier material, and the surfactant are mixed with water to obtain a first mixed solution; The first mixed solution is added to an oil phase under high-speed shearing to obtain a second mixed solution; the mass ratio of the oil phase to the first mixed solution is (1.5-20):1; The crosslinking agent is added dropwise to the second mixed solution to obtain the complex nanogel sustained-release agent; The oil phase is one or more of cyclohexane, isopropyl alcohol, rapeseed oil, dimethylbenzene, methyl oleate, 200# solvent oil, and methyl esterified soybean oil; The dropping speed is 30-60 drops / min.

2. The nano-hydrogel composite slow-release agent according to claim 1, wherein, The raw materials include the following mass percentages: 1-50% of an effective component, 25-85% of a carrier material, 1-17% of a crosslinking agent, and 0.2-10% of a surfactant.

3. A process for the preparation of the complex nanogel sustained release agent according to any one of claims 1-2, characterized by, The method includes the following steps: The bromonitromethanol, the synergist, the carrier material, and the surfactant are mixed with water to obtain a first mixed solution; The first mixed solution is added to an oil phase under high-speed shearing to obtain a second mixed solution; the mass ratio of the oil phase to the first mixed solution is (1.5-20):1; The crosslinking agent is added dropwise to the second mixed solution to obtain the complex nanogel sustained-release agent; The oil phase includes one or more of cyclohexane, isopropyl alcohol, rapeseed oil, dimethylbenzene, methyl oleate, 200# solvent oil, and methyl esterified soybean oil; The dropping speed is 30-60 drops / min.

4. The use of the complex nanogel sustained-release agent according to any one of claims 1-2 or the complex nanogel sustained-release agent prepared by the preparation method of claim 3 in the prevention and treatment of plant bacterial diseases, characterized in that, The bacterial diseases are bacterial wilt, angular leaf spot, stem rot, and white leaf wilt; and the application amount of the complex nanogel sustained-release agent is 2-50 g a.i. / mu.

5. A method for controlling a bacterial disease of plants, characterized by, The method is spraying, drip irrigation, root irrigation, spreading, hole application, or seed dressing; the bacterial diseases are bacterial wilt, angular leaf spot, stem rot, and white leaf wilt; and the application amount of the complex nanogel sustained-release agent is 2-50 g a.i. / mu.

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