Preparation method of prothioconazole microgel pesticide for wheat red enzyme disease

Abstract

The invention relates to a preparation method of a prothioconazole microgel pesticide for wheat red enzyme disease, and belongs to the technical field of pesticide formulation processing. The preparation method comprises the following operation steps: (1) forming a dynamic covalent bond boric acid ester bond by utilizing a boric acid group and a substance with a 1, 2 or 1, 3-diol structure, promoting agglomeration of an alginic acid chain, and grafting phenylboronic acid onto sodium alginate to prepare phenylboronic acid sodium alginate; and (2) adding the prothioconazole solution into the phenylboronic acid sodium alginate solution, and carrying out self-assembly to obtain the granular prothioconazole microgel pesticide with the drug loading ratio of greater than 14.0%. The prepared prothioconazole microgel pesticide is good in biological activity and has low EC50 on wheat scab bacteria, it is indicated that the same sterilization effect can be achieved with a smaller dosage, the inhibition rate of prothioconazole on wheat scab is increased, in addition, the targeting property and the photolysis resisting effect of prothioconazole are improved, and the prothioconazole microgel pesticide has good application prospects. Good application prospects and market potentials are realized.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticide formulation processing, and particularly relates to a method for preparing a prothioconazole microgel pesticide for treating wheat erythrocyte sedimentation disease. Technical Background

[0002] Prothioconazole is a highly efficient and broad-spectrum triazole thione fungicide with protective, therapeutic and eradication effects. It is very promising for controlling wheat fusarium head blight. At present, the main formulations are suspension concentrates, dispersible oil suspension concentrates and emulsifiable concentrates for export. On the one hand, the target utilization rate of traditional pesticide formulations is low, and the utilization rate on crops is less than 30%. The dosage and application frequency of pesticides are increasing, resulting in more and more serious risks of pesticide residues. On the other hand, most traditional pesticides are insoluble in water, so they need to be dissolved in organic solvents and a large amount of adjuvants and surfactants are added to facilitate spraying and application. It is inevitable that pesticide products contain a large amount of toxic organic solvents, causing environmental pollution and harm. In addition, prothioconazole is easy to photolyze, and traditional formulations expose the active ingredients to the open environment for a long time, further reducing its utilization rate. Therefore, the development of a new formulation of prothioconazole that is efficient, simple, green, safe and environmentally friendly has practical application value for improving the targeting and utilization rate of prothioconazole and reducing environmental pollution.

[0003] Functionalized pesticide carriers are designed and developed according to the occurrence patterns, action characteristics and environmental conditions of harmful organisms. They use the interaction between pesticide molecules and carrier materials to achieve physical protection and controlled release of pesticide molecules, which is of great significance for improving the effective utilization rate and safety of pesticides. Among them, the design of water-based preparation of pesticides by supramolecular self-assembly technology avoids tedious chemical synthesis. At the same time, due to the dynamic reversible non-covalent interaction, pesticides can be accurately released under different stimuli. Sodium alginate is a natural polyanionic polysaccharide that exists in large quantities in nature. It has the advantages of low price, easy availability and biodegradability. It is an ideal carrier for the development of environmentally friendly pesticides. Although there have been cases of preparing related pesticide carriers by modifying sodium alginate, it does not have the improvement of the anti-photolysis and pH response properties of pesticides. In view of the characteristic that pathogenic fungi release acidic compounds and reduce the pH value of the biological microenvironment during the process of infecting plants, 3-aminophenylboronic acid is grafted into sodium alginate as a hydrophobic group. The boric acid group can form a dynamic covalent borate ester bond with a 1,2 or 1,3-diol structure substance, accelerating the self-assembly of the alginate chain. At the same time, the abundant carboxyl and hydroxyl groups on the alginate chain form hydrophobic forces, electrostatic interactions and hydrogen bonds between the carrier and prothioconazole. In addition, the borate ester bond is unstable under acidic conditions, giving the drug-loaded particles acid-responsive release characteristics. This drug-loaded system improves the targeting of prothioconazole, protects prothioconazole from photolysis, and has excellent antibacterial activity, with broad application value and market potential. Summary of the invention

[0004] In order to improve the targeting, utilization rate and anti-photolysis effect of prothioconazole and reduce environmental pollution, the present invention provides a method for preparing a prothioconazole microgel pesticide for wheat hematoxylin and eosinophilia.

[0005] The preparation steps of a prothioconazole microgel pesticide for wheat hematoxylin and eosinophilia are as follows:

[0006] (1) Preparation of phenylborated sodium alginate

[0007] (1.1) Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) to the sodium alginate solution and react for 0.5 to 1 h to obtain an activated reaction solution;

[0008] (1.2) adding 3-aminophenylboronic acid (PBA) to the activation reaction solution, stirring and reacting at room temperature for 24 h; dialyzing with pure water, and freeze-drying the dialyzate to obtain phenylboronic acid sodium alginate;

[0009] The mass ratio of the sodium alginate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 3-aminophenylboronic acid is 0.5-2.0: 0.5-1: 0.2-0.5;

[0010] (2) Preparation of prothioconazole microgel

[0011] (2.1) Dissolve prothioconazole in ethanol to obtain a prothioconazole ethanol solution with a concentration of 1 to 5 mg / mL;

[0012] (2.2) Dissolve phenylborated sodium alginate in pure water to obtain a phenylborated sodium alginate solution with a concentration of 2 to 10 mg / mL;

[0013] (2.3) Under ultrasonic conditions, slowly add the prothioconazole ethanol solution to the phenylborated sodium alginate solution, stir to react, and obtain a mixed solution; ultrafilter and centrifuge the mixed solution to obtain the prothioconazole microgel pesticide;

[0014] The prothioconazole microgel pesticide is a granular pesticide, the particles are spherical, monodispersed, evenly distributed, without obvious adhesion, the particle size is 200-900 nm, and the drug loading rate is 14.43%.

[0015] The further technical solution is as follows:

[0016] In step (1), the mass ratio of sodium alginate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 3-aminophenylboronic acid is 1:0.96:0.39.

[0017] In step (1.2), the dialysis molecular weight was 3500, the dialysis lasted for 7 days, and the pure water was replaced every day.

[0018] In step (2.1), the mass volume ratio of prothioconazole to ethanol is 3 g:100 mL.

[0019] In step (2.2), the mass volume ratio of the phenylborated sodium alginate and pure water is 6 g:200 mL.

[0020] In step (2.3), the ultrasonic conditions are: power 600 W, time 20 min.

[0021] In step (2.3), the ultrafiltration centrifugation is an ultrafiltration centrifugation with a molecular weight of 3500 Da.

[0022] The beneficial technical effects of the present invention compared with the prior art are embodied in the following aspects:

[0023] 1. The preparation method of the present invention has simple process, mild conditions, low production cost, and sodium alginate is easy to degrade. No auxiliary agent and organic solvent are used, and it is an environmentally friendly pesticide formulation.

[0024] 2. The prothioconazole microgel pesticide prepared by the present invention is spherical granules, in a monodisperse state, evenly distributed, without obvious adhesion, and has a particle size range of 200-900 nm. The sodium alginate modified by phenylboronic acid in the present invention has amphiphilicity, so that hydrophobic forces, electrostatic interactions and hydrogen bonds are formed between the carrier and prothioconazole, and ultrasound can promote the recombination of hydrogen bonds in the self-assembly system and promote the self-assembly between the carrier and the drug.

[0025] 3. In the present invention, the boric acid group can form a dynamic covalent borate ester bond with a substance having a 1,2 or 1,3-diol structure, promote the aggregation of the phenylborated alginate chain, and form a regular self-assembled structure. The present invention utilizes the characteristic that pathogenic fungi release acidic compounds during the process of infecting plants. The dynamic covalent borate ester bond is unstable and breaks under acidic conditions, thereby realizing the acid-responsive release characteristics of the drug-loaded particles. Since the modified alginate chain wraps prothioconazole in its body, the microgel has an anti-photolysis effect.

[0026] 4. The prothioconazole microgel pesticide prepared by the present invention has good biological activity. The EC of prothioconazole microgel pesticide and commercially available dispersible oil suspension against wheat fusarium 50 The prothioconazole microgels have lower EC values ​​than the commercial formulations, which are 1.39 and 2.15 mg / L, respectively. 50 , indicating that it can achieve the same fungicidal effect with less dosage, improve the inhibition rate of prothioconazole on wheat fusarium rust, and has good application prospects and market potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 These are the H NMR spectra of sodium alginate and sodium alginate modified with benzene borate; a is sodium alginate, and b is sodium alginate modified with benzene borate.

[0028] Figure 2 This is a schematic diagram of the results of determining the critical micelle concentration of phenylborated sodium alginate;

[0029] Figure 3 The transmission electron microscope and scanning electron microscope images of the prothioconazole microgel obtained in Example 1;

[0030] Figure 4 This is a structural feature analysis diagram of the prothioconazole microgel obtained in Example 1;

[0031] Figure 5 This is a thermogravimetric curve of the prothioconazole microgel obtained in Example 1;

[0032] Figure 6 The release curves of the prothioconazole microgel obtained in Example 1 under different conditions;

[0033] Figure 7 This is the photolysis resistance diagram of the prothioconazole microgel obtained in Example 1;

[0034] Figure 8 This is an experimental diagram of the antibacterial activity of the prothioconazole microgel and prothioconazole dispersible oil suspension prepared in Example 1 against wheat fusarium head blight; MGs: prothioconazole microgel, OD: prothioconazole dispersible oil suspension.

[0035] Fig. 9 The graph shows the inhibition rate of prothioconazole microgel and prothioconazole dispersible oil suspension on wheat fusarium sphaeroides obtained in Example 1. MGs: prothioconazole microgel, OD: prothioconazole dispersible oil suspension. DETAILED DESCRIPTION

[0036] The present invention will be further described below in conjunction with the embodiments.

[0037] Unless otherwise specified, the instruments, reagents and materials involved in the following embodiments are conventional instruments, reagents and materials already available in the prior art and can be obtained through regular commercial channels.

[0038] Example 1

[0039] The preparation steps of prothioconazole microgel are as follows:

[0040] (1) Preparation of phenylborated sodium alginate

[0041] (1.1) Dissolve 1 g of sodium alginate in 100 mL of pure water under stirring at room temperature, add 0.96 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and stir thoroughly for 30 min to obtain an activation reaction solution;

[0042] (1.2) Gradually add 0.39 g of 3-aminophenylboronic acid and stir the mixture at room temperature for 24 h. Place the solution after the reaction in a dialysis bag and place it in pure water for 7 days, replacing the pure water every day. Freeze-dry the dialyzed sample to obtain phenylboronic acid-modified sodium alginate, which is then sealed and stored at 4°C.

[0043] The mass ratio of sodium alginate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 3-aminophenylboronic acid is 1:0.96:0.39.

[0044] See also Figure 1 The chemical shift of 7.3-7.7 ppm is the characteristic signal of phenylboronic acid, which indicates that the phenylboronic acid fragment is successfully grafted onto sodium alginate (Alg). The substitution degree of sodium alginate is calculated by the ratio of the integral of phenylboronic acid to sodium alginate (Alg), which is about 20%.

[0045] See also Figure 2 A in the figure uses pyrene as a fluorescent probe and uses fluorescence spectrophotometry to determine the critical micelle concentration (CMC) of phenylboronic acid sodium alginate. The fluorescence emission spectrum of the pyrene probe has five emission peaks at 373 nm, 379 nm, 384 nm, 390 nm and 410 nm, among which the intensity ratio of I1 (373 nm) and I3 (384 nm) is very sensitive to the microenvironment of pyrene. Therefore, the value of I1 / I3 is usually used to characterize the polarity of the solution in which the pyrene probe is located. The sudden drop in I1 / I3 corresponds to the critical micelle concentration. The relationship between the fluorescence luminosity and I1 / I3 value of different concentrations of Alg-PBA after self-aggregation in aqueous solution is shown in the figure. Figure 2 As shown in Figure B, the CMC of phenylborated sodium alginate is 0.16 mg / mL. The smaller the CMC value, the easier it is for the polymer to self-aggregate, and the better the stability of the aggregates. Therefore, it is shown that phenylborated sodium alginate can self-aggregate at a lower concentration. Figure 2 C and Figure 2 D in the figure, the morphology and particle size of phenylborated sodium alginate micelles were characterized by transmission electron microscopy and nanoparticle size analyzer, and the average particle size was 512.9 nm.

[0046] (2) Preparation of prothioconazole microgel

[0047] (2.1) Dissolve 30 mg of prothioconazole in 10 mL of ethanol to obtain a 3 mg / mL prothioconazole ethanol solution;

[0048] (2.2) Dissolve 120 mg of phenylborated sodium alginate in 20 mL of pure water to obtain a 6 mg / mL phenylborated sodium alginate solution;

[0049] (2.3) Add the prothioconazole solution to the phenylboronic acid sodium alginate solution and sonicate at 600 W for 20 min. Transfer the solution to an ultrafiltration centrifuge tube with a molecular weight of 3500 Da and centrifuge at 5000 rpm for 30 min. Centrifuge three times to remove ethanol and unassembled small molecules to obtain prothioconazole microgel pesticide.

[0050] The prothioconazole microgel pesticide prepared in Example 1 is a granular pesticide, the particles are spherical, monodisperse, uniformly distributed, without obvious adhesion, and the particle size is 200-900 nm; the drug loading rate is 14.43%.

[0051] Example 2

[0052] According to the preparation method of Example 1, the amounts of phenylborated sodium alginate and prothioconazole were changed to prepare prothioconazole microgels with different drug loading amounts.

[0053] The absorbance of the drug was tested by ultraviolet spectrophotometer to calculate its drug loading. The dosage of prothioconazole and phenylborated sodium alginate and the drug loading of prothioconazole microgel are shown in Table 1.

[0054] Table 1 Dosages of phenylborated sodium alginate and prothioconazole and drug loading of prothioconazole microgels

[0055] Prothioconazole / mg Sodium alginate phenylborated / mg Quality Ratio Drug loading / % 30 60 1:2 15.28 30 120 1:4 14.43 20 120 1:6 10.76 15 120 1:8 8.19 12 120 1:10 6.62

[0056] From the results in Table 1, it can be seen that by adjusting the ratio of pesticide to carrier, it is found that the drug loading is higher when the ratio of pesticide to carrier is 1:4. Continuing to increase the pesticide ratio does not increase the drug loading significantly and will lead to drug waste.

[0057] See also Figure 3 , Figure 3 A in the figure is a scanning electron micrograph of prothioconazole microgel; Figure 3 B in the figure is a transmission electron microscope image of prothioconazole microgel. It can be seen from the figure that the gel particles are spherical, evenly distributed, and have no obvious adhesion phenomenon.

[0058] See also Figure 4 , Figure 4 A in is the infrared absorption spectrum, Figure 4 B in the figure is the particle size distribution diagram. Figure 4 Compared with sodium alginate, A in the sample is modified with phenylboronic acid. Figure 4 A in 1340 cm -1 The 709 cm-1 The peak at 1622 cm is the CH bending vibration of benzene. -1 The characteristic peaks are caused by the C=O stretching vibration of amide I. These characteristic peaks represent that the phenylboronic acid fragments are successfully grafted onto the alginate chain. At the same time, prothioconazole was observed on the prothioconazole microgel at 750 cm -1 (C-Cl stretching vibration) and 1500-1413 cm -1 The characteristic peaks at , indicating that prothioconazole was successfully loaded. In addition, the spectra of prothioconazole microgel and phenylborated sodium alginate are basically consistent, indicating that the main core of prothioconazole microgel is phenylborated sodium alginate (Alg-PBA), and prothioconazole is encapsulated in phenylborated sodium alginate. The position and shape of these characteristic peaks do not change significantly, but the relative intensity is significantly reduced. It can be inferred that the free vibration of prothioconazole in the phenylborated sodium alginate cavity is restricted by van der Waals forces and spatial constraints, and the molecular transition dipole moment is smaller than the free vibration dipole moment, which will lead to a decrease in infrared absorption intensity. See Figure 4 In B, after adding prothioconazole, the particle size increased from 512.9 nm to 543.2 nm, which further proved the successful encapsulation of prothioconazole.

[0059] See also Figure 5 For prothioconazole microgel, the mass loss in the first stage occurs at 30-122°C, which is mainly caused by the evaporation of adsorbed water vapor and crystal water; the second stage occurs between 122-560°C, and the mass loss in this stage is mainly caused by the depolymerization of alginate chains, decomposition of pyranose rings, and ring-opening reactions; and in the third stage, after the temperature is higher than 560°C, the mass loss corresponds to the further decomposition of carbonization products and the removal of residual volatiles. The final residual weights of prothioconazole, phenylborated sodium alginate, and prothioconazole microgel were 15.58%, 24.75%, and 27.03%, respectively, among which prothioconazole microgel had the highest value. Prothioconazole may play a role similar to that of an azo initiator, enhancing the cross-linking reaction of free radicals in the alginate chain and improving the thermal stability of prothioconazole microgel. See Figure 5 In Figure B, the endothermic process of prothioconazole microgel in the DTA curve occurs at about 137.7°C, which is higher than 131.4°C of prothioconazole, which may be related to the destruction of the binding force (such as hydrogen bond) between prothioconazole and phenylborated sodium alginate. The above shows that prothioconazole and phenylborated sodium alginate form composite microgel particles through non-covalent interaction.

[0060] In vitro release of prothioconazole from prothioconazole microgels

[0061] To evaluate the release performance of prothioconazole in prothioconazole microgels, release experiments were conducted under different pH conditions (5, 7, and 9). The prothioconazole microgels were added into dialysis bags (3500 Da), and the dialysis bags were placed into beakers containing 150 mL of release medium, which consisted of PBS with 70% water and 30% methanol. Different pH release conditions were controlled, and under room temperature and in a dark environment, sustained release was carried out with constant stirring at 150 rpm / min. At specific time points, 1 mL of the sustained release solution was taken for detection, and an equal volume of release medium was added. High-performance liquid chromatography was used to measure the cumulative release rate of prothioconazole microgels.

[0062] See Figure 6 , since pathogenic fungi release acidic compounds during the process of infecting plants, reducing the pH value of the biological microenvironment, a pH-responsive release experiment was specifically designed for the acidic fungal growth environment. See Figure 6 , the prothioconazole microgels exhibited special pH-sensitive release characteristics, with an accelerated release rate under acidic conditions. In the release environment with a pH of 5, obvious release was observed in the initial stage, and the release amount reached 75% at 4 h. In the release environment with a pH of 9, the release amount reached 80% at 8 h. In the release environment with a pH of 7, the release amount reached 75% at 10 h. This indicates that the release rate of PTC under acidic conditions is faster than that under neutral and alkaline conditions. Therefore, the release behavior can be regulated by controlling the pH value.

[0063] The release kinetics model was introduced to analyze the release kinetics of prothioconazole microgels under different conditions. As shown in Table 2, the fitting results of the release kinetics model indicated that: in the release environments under different pH conditions, compared with the zero-order, first-order, and Higuchi release models, its release performance was more in line with the Weibull model, and the correlation coefficients (R 2 ) were 0.9989, 0.9988, and 0.9979 respectively. The exponent k in the Weibull model is an indicator of the release mechanism, where k ≤ 0.75 belongs to Fickian diffusion, 0.75 < k < 1 belongs to the collective mechanism of Fickian diffusion and Case II transport, and k > 1 belongs to a complex release mechanism. For prothioconazole microgels, all k values were < 0.75, indicating that its release behavior conforms to Fickian diffusion from the inner layer to the outer layer.

[0064] Table 2 Analysis of the fitting results of prothioconazole release from prothioconazole microgels under different conditions

[0065] 30% methanol (pH=5) <![CDATA[R 2 ]]> 30% methanol (pH=7) <![CDATA[R 2 ]]> 30% methanol (pH=9) <![CDATA[R 2 ]]> Zero-order model Q=0.0571t+0.3316 0.7245 Q=0.0566t+0.2225 0.8305 Q=0.0634t+0.2169 0.8624 First-order model Q=0.8521(1-exp(-0.5886t)) 0.9959 Q=0.7663(1-exp(-0.3972t)) 0.9931 Q=0.8458(1-exp(-0.3399t)) 0.9923 Higuchi Model <![CDATA[Q=0.2473t 1 / 2 +0.1274]]> 0.8838 <![CDATA[Q=0.2392t 1 / 2 +0.0319]]> 0.9521 <![CDATA[Q=0.2655t 1 / 2 +0.0082]]> 0.9679 Weibull Model <![CDATA[Q=0.8657(1-exp(-(0.5379(x+0.0399)) 0.9188 ))]]> 0.9989 <![CDATA[Q=0.8195(1-exp(-(0.3348(x-0.0353)) 0.8037 ))]]> 0.9988 <![CDATA[Q=0.9041(1-exp(-(0.2792(x+0.0486)) 0.8616 ))]]> 0.9979

[0066] Study on the photodegradation resistance performance of prothioconazole microgels

[0067] Prothioconazole is prone to photolysis under ultraviolet irradiation, which seriously affects its efficacy. Therefore, the UV stability of prothioconazole microgel was studied. 100 μL of prothioconazole microgel and commercially available dispersible oil suspension with the same active ingredient content were evenly applied on the surface of a glass slide, dried naturally in the dark, and then irradiated with a 14 W ultraviolet lamp. The glass slide was taken out after different irradiation times. The prothioconazole residue in the glass slide was extracted by acetonitrile extraction and analyzed by high performance liquid chromatography.

[0068] See also Figure 7 The degradation rate of prothioconazole in prothioconazole microgel was significantly lower than that of commercial dispersible oil suspension. The degradation rate of commercial dispersible oil suspension was about 62.45% in 12 h, while the degradation rate of prothioconazole microgel was 31.7%. This may be due to the rich hydroxyl and carboxyl functional groups on phenylborated sodium alginate, and these copolymer structures have the ability to absorb ultraviolet rays.

[0069] Study on the biological activity of prothioconazole microgel against wheat scab

[0070] In order to determine the biological activity of the prepared prothioconazole microgel, wheat fusarium was selected as the test strain, and the antibacterial activity was determined by the mycelial growth rate method, and the commercially available dispersible oil suspension of prothioconazole was used as a control. A 6 mm diameter bacterial cake was cut from the edge of the colony that had grown for 5 days, and then inoculated in the center of a 90 mm diameter potato dextrose agar medium containing different concentrations of prothioconazole. The blank group was a medium without drug addition, and each treatment was repeated three times. The mycelium of each treatment group grew in a constant temperature incubator at 25 ± 1 ° C under dark conditions. When the diameter of the blank treatment colony was close to the diameter of the full-grown culture dish, the antibacterial activity of each treatment was measured by the cross method. The inhibition rate was calculated by the following equation, where d c is the diameter of the control colony, d t is the colony diameter of each treatment.

[0071]

[0072] See also Figure 8 , Experimental diagram of the antibacterial activity of prothioconazole microgel particles and prothioconazole dispersible oil suspension concentrates at different concentrations against wheat fusarium sphaeroides.

[0073] See also Fig. 9, the inhibition rate of prothioconazole microgel and prothioconazole dispersible oil suspension on wheat fusarium. The corresponding inhibition rate was calculated by measuring the colony diameter of wheat fusarium on the culture medium from 24 h to 96 h. The results showed that both prothioconazole microgel particles and prothioconazole dispersible oil suspension showed excellent biological activity, and the antibacterial activity against wheat fusarium was dose- and time-dependent, increasing with the increase of concentration and time. In addition, under the same conditions, the inhibition rate of prothioconazole microgel on the mycelial growth of fusarium was always higher than that of commercial dispersible oil suspension. When the concentration of active ingredient was 10 mg / L, the mycelial growth inhibition rate of OD treatment was 75.00±1.77% after 96 h of culture, while the mycelial growth inhibition rate of MGs treatment was 83.04±1.73%. The half effective concentration (EC50) of prothioconazole microgel and commercial dispersible oil suspension on wheat fusarium was calculated. 50 ) were 1.39 and 2.15 mg / L, respectively. In summary, the therapeutic effect of MGs has good sustained release performance and has better inhibitory effect compared with the commercially available product PTC OD.

[0074] Dosage form Regression equation (y=) <![CDATA[EC 50 (mg / L)]]> 95% Confidence Interval <![CDATA[R 2 ]]> Prothioconazole microgel (PTC OD) 1.9951x-0.6651 2.15 1.68-2.81 0.9830 Prothioconazole dispersible oil suspension concentrates (PTC MGs) 2.1136x-0.3043 1.39 1.10-1.77 0.9920

[0075] The above research results show that compared with the currently widely sold prothioconazole dispersible oil suspension, the prothioconazole microgel prepared by the present invention has better and more lasting antibacterial effect, a pH-responsive release mechanism and anti-photolysis performance, and is simple to operate and has a low preparation cost, which shows that the pesticide preparation prepared by the present invention has certain advantages and has the potential for further development and application.

[0076] It will be easily understood by those skilled in the art that the above embodiments are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a prothioconazole microgel pesticide for wheat hematoxylin and eosinophilia, characterized in that: The steps are as follows: (1) Preparation of phenylborated sodium alginate (1.1) Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) to the sodium alginate solution and react for 0.5 to 1 h to obtain an activated reaction solution; (1.2) adding 3-aminophenylboronic acid (PBA) to the activation reaction solution, stirring and reacting at room temperature for 24 h; dialyzing with pure water, and freeze-drying the dialyzate to obtain phenylboronic acid sodium alginate; The mass ratio of the sodium alginate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 3-aminophenylboronic acid is 0.5-2.0: 0.5-1: 0.2-0.5; (2) Preparation of prothioconazole microgel (2.1) Dissolve prothioconazole in ethanol to obtain a prothioconazole ethanol solution with a concentration of 1 to 5 mg / mL; (2.2) Dissolve phenylborated sodium alginate in pure water to obtain a phenylborated sodium alginate solution with a concentration of 2 to 10 mg / mL; (2.3) Under ultrasonic conditions, slowly add the prothioconazole ethanol solution to the phenylborated sodium alginate solution, stir to react, and obtain a mixed solution; ultrafilter and centrifuge the mixed solution to obtain the prothioconazole microgel pesticide; The prothioconazole microgel pesticide is a granular pesticide, the particles are spherical, monodispersed, evenly distributed, without obvious adhesion, the particle size is 200-900 nm, and the drug loading rate is 14.43%.

2. A method for preparing a prothioconazole microgel pesticide for wheat hematoxylin according to claim 1, characterized in that: In step (1), the mass ratio of sodium alginate, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 3-aminophenylboronic acid is 1:0.96:0.

39.

3. A method for preparing a prothioconazole microgel pesticide for wheat hematoxylin according to claim 1, characterized in that: In step (1.2), the dialysis molecular weight was 3500, the dialysis lasted for 7 days, and the pure water was replaced every day.

4. The method for preparing a prothioconazole microgel pesticide for wheat hematoxylin according to claim 1, characterized in that: In step (2.1), the mass volume ratio of prothioconazole to ethanol is 3 g:100 mL.

5. The method for preparing a prothioconazole microgel pesticide for wheat hematoxylin according to claim 1, characterized in that: In step (2.2), the mass volume ratio of the phenylborated sodium alginate and pure water is 6 g:200 mL.

6. The method for preparing a prothioconazole microgel pesticide for wheat hematoxylin according to claim 1, characterized in that: In step (2.3), the ultrasonic conditions are: power 600 W, time 20 min.

7. The method for preparing a prothioconazole microgel pesticide for wheat hematoxylin according to claim 1, characterized in that: In step (2.3), the ultrafiltration centrifugation is an ultrafiltration centrifugation with a molecular weight of 3500 Da.

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