A pH-responsive pesticide controlled-release microsphere and a preparation method thereof

Abstract

The present application relates to the field of pesticide preparation and controlled release material, in particular to a pH-responsive pesticide controlled release microsphere and a preparation method thereof; the microsphere comprises a core material containing a pesticide active ingredient, and a three-dimensional network wall material shell formed by in-situ crosslinking of a polymer matrix containing free amino groups and a multifunctional macromolecular crosslinking modifier; the core is a modified agent synthesized by grafting a hydrazine compound containing a 3,4-dihydroxyphenyl group on a polyaldehyde polymer skeleton, so that the wall material network contains a hydrazone bond, an imine bond and a 3,4-dihydroxyphenyl group at the same time; the present application overcomes the defects that the traditional static crosslinking network is easy to leak and cannot effectively respond to stimulation, solves the problems of neutral burst release, slow acid response and weak leaf spreading and adhesion of the microsphere by using double dynamic covalent bonds and biomimetic adhesion structures, realizes acid-responsive controlled release, and significantly improves the rainstorm erosion resistance, ultraviolet attenuation resistance and soil degradability of the microsphere.

Description

Technical Field

[0001] This invention relates to the field of pesticide formulations and controlled-release materials, specifically to a pH-responsive pesticide controlled-release microsphere and its preparation method. Background Technology

[0002] In agricultural production, traditional pesticide formulations suffer from problems such as susceptibility to environmental influences leading to burst release, slow response under acidic conditions, and poor leaf adhesion. Existing technologies often employ static cross-linked networks to prepare controlled-release microspheres, but these microspheres are prone to structural loosening and leakage under prolonged neutral water conditions, and cannot effectively utilize dynamic covalent bond dissociation to release the drug under acidic stimulation. Furthermore, traditional microspheres lack an effective adhesion mechanism to plant leaves, making them susceptible to erosion by heavy rain. Therefore, how to provide a pesticide controlled-release microsphere that balances high encapsulation efficiency, precise acid-responsive release, and high leaf adhesion with erosion resistance is a technical problem urgently needing to be solved by those skilled in the art. Summary of the Invention

[0003] The purpose of this invention is to provide a pH-responsive pesticide controlled-release microsphere and its preparation method, aiming to solve the problems in existing technologies where the crosslinking density is difficult to precisely control, leading to a loose structure and leakage under neutral conditions, and where the dissociation response is slow under acidic stimulation, lacking an effective adhesion mechanism to plant leaves. Specifically, the technical solution of this invention is as follows: A pH-responsive pesticide controlled-release microsphere, the microsphere having a core-shell structure, comprising: Core material: contains active pesticide components; Wall material: is a three-dimensional network polymer shell formed by in-situ covalent crosslinking of a polymer matrix containing free amino groups and a multifunctional macromolecular crosslinking modifier; wherein, the network nodes of the three-dimensional network polymer shell contain imine bonds formed by the condensation of amino groups in the polymer matrix and aldehyde groups in the crosslinking modifier; and the network skeleton of the wall material simultaneously contains hydrazone bonds and 3,4-dihydroxyphenyl groups.

[0004] Preferably, the multifunctional macromolecular crosslinking modifier is prepared by grafting a hydrazide compound containing 3,4-dihydroxyphenyl onto the aldehyde groups in the multialdehyde polymer as a backbone.

[0005] Preferably, the method includes the following steps: Step 1, preparation of the polyaldehyde polymer skeleton: dissolve the polymer precursor in deionized water, add an oxidant under light-protected conditions, and carry out an oxidation reaction at 20-25°C for 12-24 hours; after the reaction is completed, add ethylene glycol to quench the unreacted oxidant, and after dialysis and freeze-drying, obtain a polyaldehyde polymer skeleton rich in free aldehyde groups. Step 2, Synthesis of multifunctional macromolecular crosslinking modifier: Dissolve hydrazide compounds containing 3,4-dihydroxyphenyl in a weakly acidic buffer solution, add an aqueous solution containing the polyaldehyde polymer backbone prepared in Step 1, control the molar ratio of hydrazide groups to aldehyde groups in the polyaldehyde polymer backbone to be 0.2:1 to 0.3:1, react at 20-25℃ for 6-8 hours to obtain a multifunctional macromolecular crosslinking modifier with hydrazone bonds in the main chain and retaining free aldehyde groups; Step 3, in-situ assembly and cross-linking curing of microspheres: The active ingredient of pesticide is dissolved in an organic solvent as the oil phase and added to an acidic aqueous solution containing an emulsifier and a polymer matrix containing free amino groups. The mixture is then subjected to high-speed shearing to form an oil-in-water emulsion. The oil-in-water emulsion is then uniformly dropped into a weakly alkaline coagulation bath containing the multifunctional macromolecular cross-linking modifier prepared in step 2 to carry out a cross-linking curing reaction. After the reaction is completed, the product is separated to obtain the pH-responsive pesticide controlled-release microspheres.

[0006] Preferably, in step 3, the separation process specifically involves: after the reaction is completed, collecting the microspheres by centrifugation, washing them alternately with deionized water and 20% ethanol aqueous solution, and finally freeze-drying them for 24 hours to obtain microsphere powder; the centrifugation conditions are: a rotation speed of 6000 rpm and a time of 10 minutes.

[0007] Preferably, in the multifunctional macromolecular crosslinking modifier, the molar ratio of the acylhydrazine group of the acylhydrazine compound to the aldehyde group of the multialdehyde polymer is 0.2:1 to 0.3:1.

[0008] Preferably, in step 1, the polymer precursor is sodium alginate and the oxidant is sodium periodate; in step 2, the acylhydrazine compound containing 3,4-dihydroxyphenyl is 3,4-dihydroxybenzoylhydrazine; and in step 3, the polymer matrix containing free amino groups is chitosan.

[0009] Preferably, in step 2, the pH value of the weakly acidic buffer solution is 4.5-5.0.

[0010] Preferably, in step 3, the pH value of the acidic aqueous solution is 4.0; the polymer matrix containing free amino groups is chitosan; the volume ratio of the oil phase to the acidic aqueous solution is 1:5 to 1:10; and the conditions for high-speed shearing are: a shear rate of 8000-12000 rpm and a shearing time of 10-15 minutes.

[0011] Preferably, in step 3, the pH value of the weakly alkaline coagulation bath is 7.5-8.0; the conditions for the crosslinking and curing reaction are: the coagulation bath temperature is controlled at 25-35℃, the reaction is continuously stirred for 3-5 hours, and the stirring speed is 200-300 rpm.

[0012] The beneficial effects of this invention are as follows: 1. This invention utilizes a polymer matrix containing free amino groups to crosslink in situ with a multifunctional macromolecular crosslinking modifier, simultaneously introducing imine bonds and hydrazone bonds into the microsphere wall material network. This crosslinking network overcomes the defects of traditional static crosslinking, which is prone to loosening and leakage, reduces the burst release of drugs in a neutral water environment, and utilizes hydrazone bond hydrolysis to achieve dissociation of the wall material network under acidic stimulation, thereby improving the acid-responsive controlled release performance of pesticides. 2. The multifunctional macromolecular crosslinking modifier of the present invention contains 3,4-dihydroxyphenyl, which imparts adhesive properties to the microsphere wall material; this structure overcomes the technical defects of weak leaf spreading and adhesion of traditional pesticide formulations, enhances the affinity of microspheres to plant leaves, improves the resistance of microspheres to rainstorm erosion, and prolongs the residence and action time of pesticide active ingredients on the leaf surface. 3. This invention uses chitosan and sodium alginate oxidized from periodate as a backbone to assemble a dense core-shell structure in situ. This cross-linking assembly mode prevents uneven distribution of cross-linking density in the wall material, not only forming a dense coating on the internal pesticide core material to resist ultraviolet decay, but also enabling the microspheres to be degraded by the soil after application, thus possessing good ecological safety. Detailed Implementation

[0013] The technical solutions in the embodiments of the present invention will be clearly and completely described below. The described embodiments are only some embodiments of the present invention, and not all embodiments; based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example

[0014] This embodiment provides a pH-responsive pesticide controlled-release microsphere and its preparation method, which specifically includes the following steps; S1, Preparation of the multi-aldehyde polymer backbone 5.0 g of sodium alginate was dissolved in 100 mL of deionized water, and 2.8 g of sodium periodate was added under light-protected conditions. The reaction was carried out at 25 °C for 12 hours. After the reaction was completed, 1.0 mL of ethylene glycol was added to quench the reaction for 30 minutes. The mixture was then dialyzed through a dialysis bag with a molecular weight cutoff of 3500 for 48 hours and freeze-dried to obtain sodium alginate oxidized with periodate rich in free aldehyde groups. S2. Synthesis of Multifunctional Macromolecular Crosslinking Modifiers 1.0 g of sodium alginate oxidized by periodate was dissolved in 50 mL of acetate-sodium acetate buffer solution, and 0.18 g of 3,4-dihydroxybenzoyl hydrazine was added to make the molar ratio of hydrazine group to aldehyde group in sodium alginate oxidized by periodate 0.2:1. The reaction was carried out at 25 °C for 6 hours to obtain a multifunctional macromolecular crosslinking modifier with hydrazone bond in the main chain and free aldehyde group retained. S3, In-situ assembly and cross-linking curing of microspheres Chitosan was dissolved at 1.5% by mass in an aqueous solution of 1.0% by volume to prepare an acidic aqueous solution with a pH of 4.0; 0.80g of abamectin was dissolved in 8mL of ethyl acetate to form an oil phase; the oil phase was added to 40mL of an acidic aqueous solution of chitosan containing polysorbate 80 emulsifier, and the mixture was sheared at 8000rpm for 10 minutes to form an oil-in-water emulsion; The oil-in-water emulsion was added dropwise at a rate of 1.5 mL / min using a peristaltic pump to a weakly alkaline coagulation bath with a pH of 7.5 containing the aforementioned multifunctional macromolecular crosslinking modifier. The coagulation bath temperature was controlled at 25°C, and the reaction was continuously stirred for 3 hours at a stirring speed of 200 rpm. After the reaction was completed, the suspension was centrifuged at 6000 rpm for 10 minutes to collect the microspheres. After removing the supernatant, the microspheres were washed once each with 20 mL of deionized water, 20 mL of 20% ethanol aqueous solution, and 20 mL of deionized water. The microspheres were then pre-frozen at -40°C for 8 hours and freeze-dried for 24 hours to obtain the pH-responsive pesticide controlled-release microsphere powder. Example

[0015] This embodiment provides a pH-responsive pesticide controlled-release microsphere and its preparation method, which specifically includes the following steps; S1, Preparation of the multi-aldehyde polymer backbone The operation process is exactly the same as in Example 1; S2. Synthesis of Multifunctional Macromolecular Crosslinking Modifiers 1.0 g of sodium alginate oxidized by periodate was dissolved in 50 mL of acetate-sodium acetate buffer solution, and 0.18 g of 3,4-dihydroxybenzoyl hydrazine was added to make the molar ratio of hydrazine group to aldehyde group in sodium alginate oxidized by periodate 0.2:1. The reaction was carried out at 25 °C for 6 hours to obtain a multifunctional macromolecular crosslinking modifier with hydrazone bond in the main chain and free aldehyde group retained. S3, In-situ assembly and cross-linking curing of microspheres The operation process is basically the same as in Example 1, except that: the core material is changed to pyraclostrobin; the volume ratio of oil phase to acidic aqueous solution is set to 1:8; the high-speed shear rate is 10,000 rpm and the shearing time is 12 minutes; the pH value of the weakly alkaline coagulation bath is 7.8 and the coagulation bath temperature is 30°C; the reaction is continuously stirred for 4 hours and the stirring speed is 250 rpm. Example

[0016] This embodiment provides a pH-responsive pesticide controlled-release microsphere and its preparation method, which specifically includes the following steps; S1, Preparation of the multi-aldehyde polymer backbone The operation process is exactly the same as in Example 1; S2. Synthesis of Multifunctional Macromolecular Crosslinking Modifiers The operation process is basically the same as in Example 1, except that: the pH value of the weakly acidic buffer solution is set to 5.0; the molar ratio of the hydrazide group to the aldehyde group in the sodium alginate oxidized by periodate is controlled to be 0.3:1; and the reaction time is 8 hours. S3, In-situ assembly and cross-linking curing of microspheres The operation process is basically the same as in Example 1, except that: the volume ratio of oil phase to acidic aqueous solution is set to 1:10; the high-speed shear rate is 12000 rpm and the shearing time is 15 minutes; the pH value of the weakly alkaline coagulation bath is 8.0 and the coagulation bath temperature is 35°C; the reaction is continuously stirred for 5 hours and the stirring speed is 300 rpm.

[0017] Comparative Example 1: The difference between this comparative example and Example 2 is that: in S2, the multifunctional macromolecular crosslinking modifier modified with 3,4-dihydroxybenzoylhydrazine is not used, and only sodium alginate oxidized from periodate prepared in S1 is used directly as the crosslinking agent. Other operation steps and process parameters are exactly the same as in Example 2. The microspheres formed in this comparative example only have an imine bond network formed by chitosan and oxidized sodium alginate. The resulting microspheres do not have hydrazone bonds or 3,4-dihydroxyphenyl bonds.

[0018] Comparative Example 2: The difference between this comparative example and Example 2 is that: in S3, the multifunctional macromolecular crosslinking modifier is not added to the coagulation bath, but instead 0.5% by mass of glutaraldehyde aqueous solution is added, the pH value of the coagulation bath is 7.8, the coagulation bath temperature is 30°C, the reaction time is 4 hours, and the stirring speed is 250 rpm. Other operating steps and process parameters are exactly the same as in Example 2. The resulting microsphere wall material is composed only of chitosan and glutaraldehyde crosslinking, and does not contain hydrazone bonds, free multialdehyde polymer backbone and 3,4-dihydroxyphenyl.

[0019] Performance testing Confocal laser scanning microscopy and scanning electron microscopy were used to observe the surface morphology and internal core-shell structure of microspheres; Fourier transform infrared spectroscopy was used to verify the characteristic peaks of hydrazone and imine bonds; X-ray photoelectron spectroscopy was used to analyze the chemical state of N1s; high performance liquid chromatography was used to determine the encapsulation efficiency and drug loading; laser particle size analyzer was used to determine the average particle size; contact angle meter was used to determine the leaf contact angle; in vitro release tests were conducted in pH 7.4 phosphate buffer and pH 5.0 acetate buffer; artificial rainfall tests were conducted by washing the sprayed leaves with 100 mm / h rain for 4 hours after drying, and the retention rate was determined after 2 hours of rain; ultraviolet aging chamber was used to determine the degradation rate after 72 hours of 315-400 nm ultraviolet irradiation; soil degradation tests were conducted by burying the microspheres in loam with a moisture content of 25% to determine the weight loss rate. The supplementary morphological observation results are as follows: Examples 1 to 3 all exhibit a distinct core-shell structure. The green fluorescence labeled with fluorescein isothiocyanate is concentrated in the shell layer of the microspheres, while the red fluorescence labeled with Nile Red is concentrated in the core. Furthermore, the cross-section of the scanning electron microscope shows a distinct hollow encapsulated morphology. Comparative Example 1 has a thinner shell than Examples 1 to 3 and exhibits poor uniformity of encapsulation. Comparative Example 2 shows no obvious core-shell layering. In Fourier transform infrared spectroscopy, Examples 1 to 3 all detected a core thickness of 1645 cm⁻¹. -1 and 1620cm -1 Characteristic absorption peaks of hydrazone and imine bonds were detected in the vicinity. In Comparative Example 1, only the imine bond peak was detected, while in Comparative Example 2, no hydrazone bond-related peaks were detected. Test Result Mechanism Analysis Structural characterization results from confocal laser scanning microscopy and scanning electron microscopy show that the present invention successfully constructed a stable wall shell by in-situ crosslinking a chitosan polymer matrix with a multifunctional macromolecular modifier. X-ray photoelectron spectroscopy further confirmed the highly crosslinked state of free amino groups converted into imine bonds in the examples, verifying the formation of a dual dynamic bond network chemical structure. In contrast, the comparative examples failed to form an ideal core-shell encapsulation morphology due to different crosslinking systems. A comparison of the test results of Examples 1-3 and Comparative Example 1 shows that the lack of 3,4-dihydroxybenzoyl hydrazine modification leads to a decrease in the release rate of microspheres to 51.4% under pH 5.0 conditions, an increase in leaf contact angle, and a decrease in retention rate to 49.8% after heavy rain. The underlying mechanism is that hydrazone bonds are the core of acid-triggered degradation. The absence of hydrazone bonds reduces the hydrolysis and pore expansion capacity of the wall material network under acidic conditions, weakening the acid-response release rate. At the same time, the lack of biomimetic adhesion of 3,4-dihydroxyphenyl causes the microspheres to lose their strong affinity and adhesion to plant leaves, resulting in reduced hydrophilic spreading performance. A comparison of the test results of Examples 1-3 and Comparative Example 2 shows that after replacing the multifunctional macromolecular crosslinking modifier with a traditional glutaraldehyde small molecule crosslinking system, the controlled-release performance and environmental adaptability of the microspheres are significantly reduced: the leakage burst release at pH 7.4 is 28.3%, while at pH 5.0, there is no effective dissociation response, the UV degradation rate increases to 18.9%, and the soil weight loss rate decreases to 21.6%. The underlying mechanism is that although the network formed by glutaraldehyde crosslinking contains imine bonds, it is prone to irreversible side reactions, resulting in an overly rigid and dense crosslinked network that loses its reversible dynamic dissociation ability. The resulting shell is prone to loosening and leakage in a neutral environment, and cannot effectively dissociate under acidic stimulation. In addition, the lack of a natural polysaccharide macromolecular backbone and antioxidant polyphenol structure reduces the microspheres' resistance to ultraviolet penetration, leading to drug photolysis. Furthermore, this irreversible and dense crosslinked network is not easily degraded by microorganisms in the soil. Based on the data from Examples 1 to 3, it can be seen that within the scope of the technical solution defined in this invention, by controlling the grafting ratio of the multifunctional modifier and the process parameters of the microsphere crosslinking assembly, the particle size, leaf surface adhesion, and acid response rate of the microspheres can be effectively controlled. Example 3 corresponds to a higher degree of functionalization, and its retention rate after heavy rain and acid-responsive release rate are superior to those of other examples and comparative examples; Example 2 has optimized comprehensive performance in terms of encapsulation efficiency, drug loading, and particle size uniformity; This indicates that the combination of chitosan, multifunctional macromolecular crosslinking modifier, hydrazone bond, imine bond, and 3,4-dihydroxyphenyl can successfully construct a dense core-shell structure in the same microsphere wall material, while taking into account multiple properties such as environmentally responsive controlled release, strong adhesion, resistance to UV decay, and soil biodegradability.

[0020] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments for application in other fields. However, any conventional modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the technical solution of the present invention shall still fall within the protection scope of the technical solution of the present invention.

Claims

1. A pH-responsive pesticide controlled-release microsphere, characterized in that, The microspheres have a core-shell structure, comprising: Core material: Contains active pesticide ingredients; Wall material: a three-dimensional network polymer shell formed by in-situ covalent crosslinking of a polymer matrix containing free amino groups and a multifunctional macromolecular crosslinking modifier; wherein, the network nodes of the three-dimensional network polymer shell contain imine bonds formed by the condensation of amino groups in the polymer matrix and aldehyde groups in the crosslinking modifier; and the network skeleton of the wall material simultaneously contains hydrazone bonds and 3,4-dihydroxyphenyl groups.

2. The pH-responsive pesticide controlled-release microspheres according to claim 1, characterized in that, The multifunctional macromolecular crosslinking modifier is prepared by grafting a hydrazide compound containing 3,4-dihydroxyphenyl onto the aldehyde groups in the multialdehyde polymer as a backbone.

3. A method for preparing pH-responsive pesticide controlled-release microspheres as described in any one of claims 1 or 2, characterized in that, The method includes the following steps: Step 1, Preparation of the polyaldehyde polymer backbone: The polymer precursor is dissolved in deionized water, and an oxidant is added under light-protected conditions. The oxidation reaction is carried out at 20-25℃ for 12-24 hours. After the reaction is completed, ethylene glycol is added to quench the unreacted oxidant. After dialysis and freeze-drying, a polyaldehyde polymer backbone rich in free aldehyde groups is obtained. Step 2, Synthesis of multifunctional macromolecular crosslinking modifier: Dissolve hydrazide compounds containing 3,4-dihydroxyphenyl in a weakly acidic buffer solution, add an aqueous solution containing the polyaldehyde polymer backbone prepared in Step 1, control the molar ratio of hydrazide groups to aldehyde groups in the polyaldehyde polymer backbone to be 0.2:1 to 0.3:1, react at 20-25℃ for 6-8 hours to obtain a multifunctional macromolecular crosslinking modifier with hydrazone bonds in the main chain and retaining free aldehyde groups; Step 3, in-situ assembly and cross-linking curing of microspheres: The active ingredient of pesticide is dissolved in an organic solvent as the oil phase and added to an acidic aqueous solution containing an emulsifier and a polymer matrix containing free amino groups. The mixture is then subjected to high-speed shearing to form an oil-in-water emulsion. The oil-in-water emulsion is then uniformly dropped into a weakly alkaline coagulation bath containing the multifunctional macromolecular cross-linking modifier prepared in step 2 to carry out a cross-linking curing reaction. After the reaction is completed, the product is separated to obtain the pH-responsive pesticide controlled-release microspheres.

4. The method according to claim 3, characterized in that, In step 3, the separation process specifically involves: after the reaction is completed, collecting the microspheres by centrifugation, washing them alternately with deionized water and 20% ethanol aqueous solution, and finally freeze-drying them for 24 hours to obtain microsphere powder; the centrifugation conditions are: a rotation speed of 6000 rpm and a time of 10 minutes.

5. The pH-responsive pesticide controlled-release microspheres according to claim 2, characterized in that, In the multifunctional macromolecular crosslinking modifier, the molar ratio of the acylhydrazine group in the acylhydrazine compound to the aldehyde group in the multialdehyde polymer is 0.2:1 to 0.3:

1.

6. The method according to claim 3, characterized in that, In step 1, the polymer precursor is sodium alginate and the oxidant is sodium periodate; in step 2, the hydrazide compound containing 3,4-dihydroxyphenyl is 3,4-dihydroxybenzoylhydrazide; in step 3, the polymer matrix containing free amino groups is chitosan.

7. The method according to claim 6, characterized in that, In step 2, the pH value of the weakly acidic buffer solution is 4.5-5.

0.

8. The method according to claim 6, characterized in that, In step 3, the pH value of the acidic aqueous solution is 4.0; the polymer matrix containing free amino groups is chitosan; the volume ratio of the oil phase to the acidic aqueous solution is 1:5 to 1:10; the conditions for high-speed shearing are: shear rate of 8000-12000 rpm and shearing time of 10-15 minutes.

9. The method according to claim 6, characterized in that, In step 3, the pH value of the weakly alkaline coagulation bath is 7.5-8.0; the conditions for the cross-linking curing reaction are: the coagulation bath temperature is controlled at 25-35℃, the reaction is continuously stirred for 3-5 hours, and the stirring speed is 200-300 rpm.