Intelligent platform type multifunctional drug dispersant, preparation method and application

Abstract

The application discloses an intelligent platform type multifunctional drug dispersant, a preparation method and application. The intelligent platform type multifunctional drug dispersant comprises an adhesive dispersant aqueous solution and a solid drug. The adhesive dispersant solute in the adhesive dispersant aqueous solution is a core-shell structure composite material. The core body is biodegradable nanoparticles, and the shell body is a nanometer film formed by polymerization of amyloid aggregates. The intelligent platform type multifunctional drug dispersant has the following excellent performances: green raw materials and biodegradability, intelligent controlled release performance, excellent hydrophobic particle dispersion capacity, ultraviolet resistance and acid rain erosion resistance, super spreading and synergistic effect, and has a wide application field and other characteristics. The preparation method uses natural proteins and biomass nanomaterials as main construction units, and uses water as a solvent in the whole preparation process, and does not involve toxic organic solvents, so that the environmental protection performance is good, and the preparation method lays a foundation for large-scale production of the intelligent platform type multifunctional drug dispersant.

Description

Technical Field

[0001] This invention belongs to the field of pesticide formulation research and development technology, specifically relating to an intelligent platform-type multifunctional drug dispersant, its preparation method, and its application. Background Technology

[0002] Agriculture is the source of human food and clothing, the foundation of survival, and the primary condition for all production. Pesticides play a vital role in agricultural development; for example, herbicides are a key means of effectively controlling weeds in farmland. However, current pesticide application still faces two major challenges: first, the rapid settling and low suspension rate of the active ingredients in the pesticide solution lead to uneven spraying, affecting efficacy and potentially causing phytotoxicity; second, pesticide solutions are prone to splashing and rebound during spraying and are easily eroded by rainwater, resulting in low pesticide utilization efficiency and secondary pollution of the ecological environment. Therefore, it is necessary to rationally design and optimize herbicide formulations to achieve their efficient utilization.

[0003] The emergence of pesticide dispersants is closely related to the development of pesticide active ingredients and the advancement of formulation processing technology. In the early stages of chemical control, pesticides were directly added to water to form a mixed system, resulting in poor dispersibility and weak adhesion. To solve these problems, researchers added wetting agents and dispersants, and mixed and pulverized the pesticide technical material with adjuvants such as dispersants and wetting agents to create water-soluble pesticide dispersants. These water-soluble pesticide dispersants, when diluted with water, form stable suspensions, facilitating spray application and significantly improving pesticide utilization and control efficacy.

[0004] Despite the advantages of existing water-dispersible pesticide formulations, the following shortcomings still exist: (1) After the pesticide solution is prepared, due to the excessive particle size of the active ingredient or filler, uneven particle size distribution, or improper selection and insufficient dosage of dispersant or wetting agent, the active ingredient settles quickly and has a low suspension rate, resulting in uneven spraying, affecting the efficacy and even inducing pesticide damage; (2) There are still varying degrees of splashing and rebound problems during the spraying process, resulting in low pesticide utilization efficiency and the risk of secondary pollution to the ecological environment; (3) Under complex environmental conditions such as ultraviolet radiation and acid rain erosion, the stability of water-dispersible pesticides is poor, the active ingredient is easily degraded, and the efficacy period is shortened; (4) There is a lack of intelligent control over the release behavior of the drug, and the superspreading ability on the hydrophobic interface is insufficient, which limits its widespread application in high-requirement precision agriculture, biomedicine and high-end manufacturing.

[0005] Therefore, there is an urgent need to develop an intelligent platform-type multifunctional drug dispersant, its preparation method, and its application to comprehensively solve the above-mentioned technical problems. Summary of the Invention

[0006] The purpose of this invention is to overcome the deficiencies in existing technologies and provide an intelligent platform-type multifunctional drug dispersant, its preparation method, and its applications. This intelligent platform-type multifunctional drug dispersant possesses excellent properties such as green raw materials and biodegradability, intelligent controlled-release performance, superior hydrophobic particle dispersion ability, resistance to UV and acid rain erosion, and super-spreading and synergistic effects. It also has a wide range of applications, including as a liquid dispersant in nano-pesticides, cosmetics, coatings, oral liquid drugs, and injectable drugs. The preparation method of this invention uses natural proteins (lysozyme, bovine serum albumin, etc.) and biomass nanomaterials (cellulose nanocrystals, nanofibers, etc.) as the main building blocks. The entire preparation process uses water as a solvent, avoiding the use of toxic organic solvents, thus exhibiting good environmental friendliness and laying the foundation for the large-scale production of intelligent platform-type multifunctional drug dispersants.

[0007] One objective of this invention is to provide a smart platform-type multifunctional drug dispersant, comprising an aqueous solution of an adhesive dispersant and a solid drug. The adhesive dispersant solute in the aqueous solution is a core-shell structured composite material, wherein the core is biodegradable nanoparticles and the shell is a nanofilm formed by the polymerization of amyloid protein aggregates.

[0008] Preferably, the thickness of the nanofilm is in the range of 1~50nm, and it is polymerized from amyloid protein aggregates with a particle size of 1~10nm; the particle size of the adhesive dispersant solute is in the range of 500~900nm and the mass concentration is 10~20mg / mL.

[0009] Preferably, the biodegradable nanoparticles are one of cellulose nanofibers, cellulose nanocrystals, lithium magnesium silicate nanosheets, and nano-silica particles; the amyloid protein aggregates are formed by the polymerization reaction of one or more of lysozyme, bovine serum albumin, insulin, and α-lactalbumin.

[0010] More preferably, the cellulose nanofibers have a diameter of 4-10 nm, a length of 1-5 μm, and a mass concentration of 0.1-6 mg / mL;

[0011] The cellulose nanocrystals have a diameter of 4-10 nm, a length of 100-500 nm, and a mass concentration of 1-30 mg / mL.

[0012] The lithium magnesium silicate nanosheets have a thickness of 1-3 nm, a lateral dimension of 25-50 nm, and a mass concentration of 1-30 mg / mL.

[0013] The particle size of the nano-silica particles is 20~200nm, and the mass concentration is 1~30mg / mL;

[0014] The mass concentration of the protein corresponding to the amyloid aggregate is 1~30 mg / mL.

[0015] Preferably, the intelligent platform-type multifunctional drug dispersant also contains a surfactant, the mass percentage of which is 0.001~1wt%.

[0016] Preferably, the solid drug is a pesticide, specifically one of pyrimimethoxam, cyhalothrin, hydrofluoric acid ester, and pyraclostrobin, with a mass percentage of 5-20 wt%.

[0017] A second objective of this invention is to provide a method for preparing the above-mentioned intelligent platform-type multifunctional drug dispersant, comprising the following steps:

[0018] S1: Preparation of aqueous solution of adhesive dispersant

[0019] Biodegradable nanoparticles were slowly added to a protein aqueous solution and stirred until homogeneous to obtain a suspension. Then, tris(2-carboxyethyl)phosphonic acid hydrochloride aqueous solution was added dropwise to the prepared suspension and stirred for a period of time under certain temperature conditions to obtain an adhesive dispersant aqueous solution.

[0020] S2: Preparation of intelligent platform-type multifunctional drug dispersants

[0021] Weigh a certain mass of solid drug and add it to the aqueous solution of the adhesive dispersant prepared in step S1. Stir and mix evenly to obtain a preliminary drug dispersant. Ultrasonically treat the preliminary drug dispersant to obtain a smart platform type multifunctional drug dispersant.

[0022] Preferably, in step S1, the molar concentration of tris(2-carboxyethyl)phosphine hydrochloride in the aqueous solution is 30-50 mmol / L, the pH is 4-5, the reaction temperature is 25-40℃, and the reaction time is 1-24 h.

[0023] More preferably, step S2 specifically involves: using an ultrasonic cell wall disruptor to pulverize the preliminary drug dispersant, with operating parameters of 20 kHz, ultrasonic power density of 300 W / cm2, and a total duration of 1-10 min.

[0024] The third objective of this invention is to provide an application of the above-mentioned intelligent platform-type multifunctional drug dispersant, which can be used as a liquid dispersant in nano-pesticides, cosmetics, coatings, oral liquid drugs, and injectable drugs.

[0025] The advantages and beneficial effects of this invention are as follows:

[0026] 1. The present invention provides a smart platform-type multifunctional drug dispersant with green raw materials and biodegradability: it uses natural proteins (lysozyme, bovine serum albumin, etc.) and biomass nanomaterials (cellulose nanocrystals, nanofibers, etc.) as the main building blocks, and uses water as a solvent throughout the preparation process, without involving toxic organic solvents; the resulting product can be degraded into harmless small molecules by microorganisms in the natural environment, completely solving the microplastic pollution problem caused by non-degradable fillers in traditional wettable drug water dispersants.

[0027] 2. This invention provides an intelligent platform-type multifunctional drug dispersant with intelligent controlled-release performance: by precisely controlling the thickness (1~50 nm) of the amyloid protein aggregate nanofilm, the drug release rate can be linearly adjusted from several hours to several weeks. The thicker the film, the longer the drug diffusion path and the slower the release. This provides a "one-click" control solution for different application scenarios (such as rapid insect control, long-lasting weed control, slow-release fertilizer, and postoperative slow-release drugs), demonstrating the intelligent characteristics of the material.

[0028] 3. The present invention provides a smart platform-type multifunctional drug dispersant with excellent hydrophobic particle dispersing ability: the amphiphilic functional groups on the surface of amyloid protein aggregates can be strongly adsorbed on the surface of hydrophobic drug particles, forming a dual stabilizing mechanism of steric hindrance and electrostatic repulsion; compared with the drug aqueous dispersion system without the addition of this dispersant, the suspension rate of hydrophobic particles is increased from less than 40% to more than 95%, and there is no sedimentation after standing for 30 days.

[0029] 4. The present invention provides a smart platform-type multifunctional drug dispersant with resistance to ultraviolet radiation and acid rain erosion: the β-sheet structure of amyloid protein aggregates has natural ultraviolet absorption capacity (especially around 280 nm), which can reduce the photodegradation rate of drugs by more than 60%; at the same time, the dense shell remains stable in the pH range of 4 to 8, effectively protecting the internal active drug ingredients from acid rain erosion. After being washed by simulated acid rain (pH=4.5), the pesticide activity retention rate is still higher than 85%, which significantly prolongs the field efficacy period.

[0030] 5. The present invention provides a smart platform-type multifunctional drug dispersant with super-spreading and synergistic effects: When the drug dispersant of the present invention is compounded with low concentration (0.05~0.2 wt%) nonionic surfactants (such as Silwet L-77, APG), compared with drug dispersants without surfactants (such as PTB / CNC drug dispersants), the spreading diameter of droplets on hydrophobic leaf surfaces (contact angle >110°) can be increased by more than 5 times, and the contact angle is as low as 8~12°, realizing a leap from "adhesion" to "super-spreading"; at the same time, the adhesive dispersant can provide strong anchoring force to prevent the spread droplets from slipping, thereby greatly improving the drug deposition efficiency.

[0031] 6. The intelligent platform-type multifunctional drug dispersant of the present invention has a wide range of applications: In addition to agricultural pesticides, the drug water dispersant of the present invention can also be used in: biomedicine, as a nanocarrier for oral or injectable hydrophobic drugs (such as paclitaxel and curcumin) to achieve controlled release; high-end coatings, added to water-based coatings to enhance the adhesion of the coating to the substrate and its anti-UV aging performance; cosmetics, used in sunscreens and foundations to improve the dispersion stability and skin adhesion of hydrophobic functional ingredients (such as physical sunscreens and pigments); and intelligent food packaging, as a biodegradable antibacterial coating to slowly release natural antibacterial agents.

[0032] 7. The present invention provides a method for preparing an intelligent platform-type multifunctional drug dispersant, which uses natural proteins (lysozyme, bovine serum albumin, etc.) and biomass nanomaterials (cellulose nanocrystals, nanofibers, etc.) as the main building blocks. The entire preparation process uses water as a solvent and does not involve toxic organic solvents, thus exhibiting good environmental friendliness. The overall operation steps are simple, the application is highly feasible, and the practicality is strong, laying the foundation for the large-scale production of intelligent platform-type multifunctional drug dispersants. Attached Figure Description

[0033] Figure 1 This is a diagram showing the dynamic changes of the aqueous dispersion system of pyrimidine oxime technical (without dispersant) under static conditions.

[0034] Figure 2 This is a diagram showing the static dynamic changes of the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1.

[0035] Figure 3 The results show the effect of cell wall disruption treatment time on the particle size of PTB / CNC adhesive pyrimimethoxam dispersant. The left figure is a biological optical microscope image, and the right figure is a curve of ultrasonic treatment time versus drug particle size.

[0036] Figure 4 The graph shows the deposition kinetics test results of water droplets and the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 on different leaf sample surfaces. The left graph corresponds to the water droplets in the control example, and the right graph corresponds to the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1.

[0037] Figure 5 A comparison of the kinetic parameters of PTB / CNC adhesive pyrimimethoxam dispersant (PTB / CNC) and water droplets on different leaf surfaces. Figure 5 (a) represents the maximum spreading ratio; Figure 5 (b) represents the maximum normalized rebound height. Detailed Implementation

[0038] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and examples. The following examples are only used to more clearly illustrate the technical solutions of the present invention and should not be construed as limiting the scope of protection of the present invention.

[0039] One objective of this invention is to provide a smart platform-type multifunctional drug dispersant, comprising an aqueous solution of an adhesive dispersant and a solid drug. The adhesive dispersant solute in the aqueous solution is a core-shell structured composite material, wherein the core is biodegradable nanoparticles and the shell is a nanofilm formed by the polymerization of amyloid protein aggregates.

[0040] Preferably, the thickness of the nanofilm is in the range of 1~50nm, and it is polymerized from amyloid protein aggregates with a particle size of 1~10nm; the particle size of the adhesive dispersant solute is in the range of 500~900nm and the mass concentration is 10~20mg / mL.

[0041] Preferably, the biodegradable nanoparticles are one of cellulose nanofibers, cellulose nanocrystals, lithium magnesium silicate nanosheets, and nano-silica particles; the amyloid protein aggregates are formed by the polymerization reaction of one or more of lysozyme, bovine serum albumin, insulin, and α-lactalbumin.

[0042] More preferably, the cellulose nanofibers have a diameter of 4-10 nm, a length of 1-5 μm, and a mass concentration of 0.1-6 mg / mL;

[0043] The cellulose nanocrystals have a diameter of 4-10 nm, a length of 100-500 nm, and a mass concentration of 1-30 mg / mL.

[0044] The lithium magnesium silicate nanosheets have a thickness of 1-3 nm, a lateral dimension of 25-50 nm, and a mass concentration of 1-30 mg / mL.

[0045] The particle size of the nano-silica particles is 20~200nm, and the mass concentration is 1~30mg / mL;

[0046] The mass concentration of the protein corresponding to the amyloid aggregate is 1~30 mg / mL.

[0047] Preferably, the intelligent platform-type multifunctional drug dispersant also contains a surfactant, the mass percentage of which is 0.001~1wt%.

[0048] Preferably, the solid drug is a pesticide, specifically one of pyrimimethoxam, cyhalothrin, hydrofluoric acid ester, and pyraclostrobin, with a mass percentage of 5-20 wt%.

[0049] A second objective of this invention is to provide a method for preparing the above-mentioned intelligent platform-type multifunctional drug dispersant, comprising the following steps:

[0050] S1: Preparation of aqueous solution of adhesive dispersant

[0051] Biodegradable nanoparticles were slowly added to a protein aqueous solution and stirred until homogeneous to obtain a suspension. Then, tris(2-carboxyethyl)phosphonic acid hydrochloride aqueous solution was added dropwise to the prepared suspension and stirred for a period of time under certain temperature conditions to obtain an adhesive dispersant aqueous solution.

[0052] S2: Preparation of intelligent platform-type multifunctional drug dispersants

[0053] Weigh a certain mass of solid drug and add it to the aqueous solution of the adhesive dispersant prepared in step S1. Stir and mix evenly to obtain a preliminary drug dispersant. Ultrasonically treat the preliminary drug dispersant to obtain a smart platform type multifunctional drug dispersant.

[0054] Preferably, in step S1, the molar concentration of tris(2-carboxyethyl)phosphine hydrochloride in the aqueous solution is 30-50 mmol / L, the pH is 4-5, the reaction temperature is 25-40℃, and the reaction time is 1-24 h.

[0055] More preferably, step S2 specifically involves: using an ultrasonic cell wall disruptor to pulverize the preliminary drug dispersant, with operating parameters of 20 kHz, ultrasonic power density of 300 W / cm2, and a total duration of 1-10 min.

[0056] The third objective of this invention is to provide an application of the above-mentioned intelligent platform-type multifunctional drug dispersant, which can be used as a liquid dispersant in nano-pesticides, cosmetics, coatings, oral liquid drugs, and injectable drugs.

[0057] Example 1

[0058] The preparation of a smart platform-type multifunctional PTB / CNC adhesive pyrimidine oxime dispersant using the method of this invention includes the following steps:

[0059] The preparation of F1, PTB / CNC adhesive dispersant aqueous solution, specifically the preparation of an adhesive dispersant (PTB / CNC) aqueous solution based on bovine serum albumin (BSA) amyloid aggregates (PTB) and cellulose nanocrystals (CNC):

[0060] Commercially available cellulose nanocrystal (CNC) dispersion (4% w / w solids) was diluted to 6 mg / mL for later use. 120 mg of bovine serum albumin (BSA) was weighed and dissolved in 3.9 mL of deionized water. Then, 2 mL of the 6 mg / mL CNC dispersion prepared above was added. Under magnetic stirring at 600 rpm, 100 μL of tris(2-carboxyethyl)phosphine (TCEP) solution (30 mmol / L, pH=4.5) was added dropwise. The reaction was continued for 12 h. TCEP induced the conversion of BSA into amyloid oligomers (PTB) by reducing the disulfide bonds in the BSA molecule. The newly generated PTB spontaneously assembled on the surface of CNC to form PTB / CNC nanocomposites, and finally 6 mL of PTB / CNC adhesive dispersant aqueous solution was obtained. The concentrations of PTB, CNC and TCEP in the PTB / CNC adhesive dispersant aqueous solution were 20 mg / mL, 2 mg / mL and 1 mmol / L, respectively.

[0061] F2. Preparation of intelligent platform-type multifunctional drug dispersants, specifically the preparation of PTB / CNC adhesive pyrimidine oxime dispersant:

[0062] 60 mg of commercially available solid herbicide pyrimiflunom (98% purity) was weighed and added to the 6 mL LTB / CNC adhesive dispersant aqueous solution prepared in step F1. The mixture was thoroughly and uniformly mixed using a vortex mixer to obtain a preliminary pyrimiflunom dispersion with a pyrimiflunom content of 10 wt%. The preliminary pyrimiflunom dispersion was then pulverized using an ultrasonic cell disruptor. Specifically, the probe (13 mm in diameter) was placed at an appropriate depth below the liquid surface, and the operating frequency was set to 20 kHz and the ultrasonic power density to 300 W / cm³. 2 The total duration was 5 minutes (2 seconds of ultrasound / 2 seconds of intermittent treatment) to reduce the particle size of pyrimidine oxime. After the pulverization process, PTB / CNC adhesive pyrimidine oxime dispersant was obtained.

[0063] Example 2

[0064] The preparation of a smart platform-type multifunctional PTB / CNF adhesive cyhalothrin dispersant using the method of this invention includes the following steps:

[0065] The preparation of H1 and PTB / CNF adhesive dispersant aqueous solutions specifically involves the preparation of an adhesive dispersant (PTB / CNF) aqueous solution based on bovine serum albumin (BSA) amyloid aggregates (PTB) and cellulose nanofibers (CNF):

[0066] The difference from step F1 in Example 1 is that a commercially available cellulose nanofiber (CNF) dispersion (6% w / w solid content) is used instead of a cellulose nanocrystal (CNC) dispersion (4% w / w solid content). In the prepared PTB / CNF adhesive dispersant aqueous solution, the concentrations of PTB, CNF, and TCEP in the PTB / CNC adhesive dispersant aqueous solution are 20 mg / mL, 6 mg / mL, and 1 mmol / L, respectively.

[0067] H2. Preparation of intelligent platform-type multifunctional drug dispersants, specifically the preparation of PTB / CNF adhesive cyhalothrin dispersants:

[0068] For specific operation, please refer to step F2 in Example 1. The difference from step F2 in Example 1 is that commercially available solid cyhalothrin is used instead of commercially available solid pyrimimethoxam, and the mass percentage of cyhalothrin in the prepared PTB / CNF adhesive cyhalothrin dispersant is 5 wt%.

[0069] Example 3

[0070] The method of this invention is used to prepare a smart platform-type multifunctional PTL / LAP adhesive hydrofluoric acid ester water dispersible agent, comprising the following steps:

[0071] The preparation of W1 and PTL / LAP adhesive dispersant aqueous solutions, specifically the preparation of adhesive dispersant (PTL / LAP) aqueous solutions based on lysozyme (LZ) amyloid aggregates (PTL) and lithium magnesium silicate nanosheets (LAP):

[0072] Dissolve 50 mg of lysozyme (LZ) in 4 mL of deionized water and stir thoroughly to form an LZ aqueous solution; disperse 10 mg of synthetic magnesium lithium silicate (LAP) in 1 mL of deionized water to obtain an LAP dispersion; mix the LZ aqueous solution and the LAP dispersion and stir on a high-speed mixer at 300 °C. Stirring at 25°C for 2 hours at a rotation speed of r / min allows LZ to be fully adsorbed onto the surface of LAP nanosheets via electrostatic interaction, forming an LZ / LAP complex. While stirring, 100 μL of tris(2-carboxyethyl)phosphine (TCEP) solution (molar concentration 50 mmol / L, pH=5) is added dropwise. After thorough mixing, the system is placed at 25°C and stirred for another 12 hours to induce an amyloid transformation of LZ and the formation of an adhesive layer on the LAP surface. This results in a PTL / LAP adhesive dispersant aqueous solution based on LZ amyloid aggregates, with concentrations of PTL, LAP, and TCEP in the PTL / LAP adhesive dispersant aqueous solution of 10 mg / mL, 1 mg / mL, and 1 mmol / L, respectively.

[0073] W2: Preparation of intelligent platform-type multifunctional drug dispersants, specifically the preparation of PTL / LAP adhesive hydrofluoric acid ester water dispersant:

[0074] For specific operation, please refer to step F2 in Example 1. The difference from step F2 in Example 1 is that commercially available solid hydrofluoric acid ester is used instead of commercially available solid pyrimimethoxam. The mass percentage of hydrofluoric acid ester in the prepared PTL / LAP adhesive hydrofluoric acid ester water dispersible agent is 15 wt%.

[0075] Example 4

[0076] The method of this invention is used to prepare a smart platform-type multifunctional PTB / LAP adhesive pyraclostrobin water dispersible agent, comprising the following steps:

[0077] Z1, the preparation of PTB / LAP adhesive dispersant aqueous solution, specifically the preparation of an adhesive dispersant (PTB / LAP) aqueous solution based on bovine serum albumin (BSA) amyloid aggregates (PTB) and lithium magnesium silicate nanosheets (LAP):

[0078] The difference from step W1 in Example 3 is that lysozyme (LZ) is replaced with bovine serum albumin (BSA), ultimately forming an aqueous solution of PTB / LAP adhesive dispersant based on PTB amyloid aggregates, wherein the concentrations of PTB, LAP, and TCEP in the PTB / LAP adhesive dispersant aqueous solution are 30 mg / mL, 30 mg / mL, and 1 mmol / L, respectively.

[0079] Z2: Preparation of intelligent platform-type multifunctional drug dispersants, specifically the preparation of PTB / LAP adhesive pyraclostrobin water dispersant:

[0080] For specific operation, please refer to step F2 in Example 1. The difference from step F2 in Example 1 is that commercially available solid pyraclostrobin is used instead of commercially available solid herbicide pyrimimethoxam. The mass percentage of pyraclostrobin in the prepared PTB / LAP adhesive pyraclostrobin water dispersible agent is 20 wt%.

[0081] Comparative Example 1

[0082] 60 mg of commercially available solid herbicide pyrimifluoxetine (98% purity) was weighed and added to 6 mL of deionized water. The mixture was thoroughly and evenly mixed using a vortex mixer to obtain a preliminary aqueous dispersion of pyrimifluoxetine, with a mass percentage of 10 wt%. The preliminary dispersion of pyrimifluoxetine was then pulverized using an ultrasonic cell disruptor. Specifically, the probe (13 mm in diameter) was placed at an appropriate depth below the liquid surface, and the operating frequency was set to 20 kHz and the ultrasonic power density to 300 W / cm³. 2The total duration was 5 min (2 s of sonication / 2 s of intermittent sonication), yielding 6 mL of pyrimidine oxime ether aqueous dispersion system.

[0083] Test Experiment 1

[0084] The dispersion stability of the PTB / CNC adhesive pyrimimethoxam dispersant prepared in Example 1 and the pyrimimethoxam aqueous dispersion system prepared in Comparative Example 1 were tested, and the specific procedures are as follows:

[0085] The PTB / CNC adhesive pyrimimethoxam dispersant prepared in Example 1 and the pyrimimethoxam aqueous dispersion system prepared in Comparative Example 1 were respectively encapsulated in bottles. After magnetic stirring, photos were taken immediately, and then the bottles were allowed to stand at room temperature for 12 hours. The standing results of the pyrimimethoxam aqueous dispersion system prepared in Comparative Example 1 are shown in the appendix. Figure 1 The standing results of the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 are shown in Appendix 1. Figure 2 .

[0086] from Figure 1 As can be seen from the images: the left image shows the state of the pyrimimethoxam aqueous dispersion system after magnetic stirring, which appears as a white suspension; the right image shows that after standing for 12 hours, the pyrimimethoxam aqueous dispersion system exhibits obvious stratification, with the pyrimimethoxam technical particles completely settling at the bottom of the bottle. This phenomenon indicates that the pyrimimethoxam aqueous dispersion system prepared in Comparative Example 1 has significant dispersion instability defects, which seriously affect the subsequent spraying and use of pyrimimethoxam.

[0087] from Figure 2 As can be seen from the diagram: the left image shows the state of the PTB / CNC adhesive pyrimidine oxime dispersant after magnetic stirring, which is a white suspension; the right image shows that after standing for 12 hours, the PTB / CNC adhesive pyrimidine oxime dispersant is still a white suspension with a consistent color from top to bottom, and no sedimentation or phase separation has occurred. This phenomenon indicates that the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 has excellent physical dispersion stability, that is, the aqueous solution of the PTB / CNC adhesive dispersant significantly improves the kinetic stability of pyrimidine oxime.

[0088] Test Experiment 2

[0089] The effect of the ultrasonic cell wall disruption machine's operating time on the particle size of pyrimimethoxam in the PTB / CNC adhesive pyrimimethoxam dispersant prepared in Example 1 was investigated. The specific operation is as follows:

[0090] Following step F1 of Example 1, a 60 mL aqueous solution of PTB / CNC adhesive dispersant was prepared by scaling up the process by 10 times. The concentrations of PTB, CNC, and TCEP in the PTB / CNC adhesive dispersant aqueous solution were 20 mg / mL, 2 mg / mL, and 1 mmol / L, respectively. Then, 600 mg of commercially available solid herbicide pyrimidine oxime (98% purity) was weighed and added to the prepared 60 mL PTB / CNC adhesive dispersant aqueous solution and stirred until homogeneous, yielding a PTB / CNC adhesive pyrimidine oxime dispersant. The prepared PTB / CNC adhesive pyrimidine oxime dispersant was divided into four equal portions. Each of the four portions was then sequentially pulverized using an ultrasonic cell disruptor. Specifically, the probe (13 mm in diameter) was placed at an appropriate depth below the liquid surface, and the operating frequency was set to 20 kHz and the ultrasonic power density to 300 W / cm³. 2 The ultrasonic pulverization times for four PTB / CNC adhesive pyrimimethoxam dispersants were 0 min, 1 min, 3 min, and 5 min, respectively, with a 2-second ultrasonic treatment followed by a 2-second intermittent treatment. The particle size of the four PTB / CNC adhesive pyrimimethoxam dispersants was then observed and photographed using a CX23 bio-optical microscope. The particle size data were plotted as an ultrasonic duration-particle size curve. The results are shown in the appendix. Figure 3 .

[0091] from Figure 3 As can be seen, with the extension of the ultrasonic cell wall disruptor treatment time, within the range of 0-3 min, the particle size of the drug (pyrimidine oxime) exhibits a significant trapezoidal decreasing trend, gradually decreasing from the initial micrometer scale (>10 μm) to the submicrometer scale (700±50 nm). Within the range of 3-5 min, the particle size decrease is relatively slow, and after 5 min, the decrease is even slower. This indicates that by precisely controlling the working time of the ultrasonic cell wall disruptor, the controllable adjustment of drug particle size from the micrometer scale to the submicrometer scale can be effectively achieved. Considering all factors, with the cell wall disruptor operating at a frequency of 20 kHz and an ultrasonic power density of 300 W / cm², this effect is particularly significant. 2 Under these conditions, a processing time of 5 minutes is optimal.

[0092] Test Experiment 3

[0093] The sedimentation kinetics of the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 were investigated. The specific procedures are as follows, with water droplets as a control:

[0094] Four different types of fresh plant leaves (barberry, bermudagrass, foxtail, and cogongrass) were selected. The leaves were gently rinsed with deionized water and dried. Several leaf samples of the same size (2cm x 4cm) were cut and fixed flat onto a glass slide with double-sided tape. An M230 high-speed camera (Revealer, China) with a macro lens (EF 100mm F / 2.8 LISUS M, China) was set on the experimental platform, with a frame rate of 2000 frames per second. By adjusting the vertical distance between the needle and the leaf sample to 20cm, droplets were allowed to fall naturally and impact the leaf surface vertically at a speed of approximately 2m / s. Simultaneously, the high-speed camera continuously recorded the deposition dynamics from droplet contact (0ms) to 48ms, including spreading, retraction, and bouncing. Each droplet and leaf sample combination was repeated at least five times, with a different fresh impact point on the leaf each time. Keyframe images at 0ms, 6ms, and 48ms were then extracted to analyze the dynamic behavior of the droplet on different leaf sample surfaces. The test results are shown in the appendix. Figure 4 .

[0095] from Figure 4 As can be seen, in the left image, the spreading angle of water droplets on the leaves of four species (barberry, bermudagrass, foxtail grass, and cogongrass) at 48ms is >60°; in the right image, the spreading angle of the PTB / CNC adhesive pyrimidine oxime ether dispersant prepared in Example 1 on the leaves of four species (barberry, bermudagrass, foxtail grass, and cogongrass) at 48ms is <25°.

[0096] To quantitatively describe the dynamic behavior of droplets, the maximum spreading ratio (β) is introduced. max = D max / D0, where D max The dynamic parameters of the two droplets on four blade surfaces were further quantitatively analyzed using two parameters: the maximum spreading diameter (D0 being the initial diameter) and the normalized rebound height (h = H / D0, where H is the droplet centroid height). The test results are shown in the appendix. Figure 5 .

[0097] from Figure 5 As can be seen from (a), in terms of spreading ability, the maximum spreading ratio (β) of PTB / CNC adhesive pyrimimethoxam dispersant droplets on crabgrass, bermudagrass, foxtail, and cogongrass is [missing information]. max The β value remained stable between 2.7 and 3.3, while that of the control example water droplet was stable. max The value is only 2.5-2.7, and the PTB / CNC adhesive pyrimidine oxime dispersant system is about 10% better than water droplets.

[0098] from Figure 5 As can be seen from (b), in terms of rebound resistance, the maximum normalized rebound height (h) of the control example water droplets on crabgrass, bermudagrass, and cogongrass is significantly higher. maxThe values ​​were generally around 0.5-0.6, reaching as high as 1.1 on foxtail grass; while the h of PTB / CNC adhesive pyrimimethoxam dispersant droplets was... max The values ​​were all below 0.5, indicating a significant reduction in rebound height, which is highly consistent with its complete deposition behavior. This demonstrates that the PTB / CNC adhesive pyrimimethoxam dispersant prepared in Example 1 can firmly adhere to the weed leaf surface during impact without rebounding, indicating that the presence of the PTB / CNC dispersant can significantly increase the adhesion of pyrimimethoxam to the weed surface.

[0099] Test Experiment 4

[0100] The PTB / CNC adhesive pyrimidine oxime dispersant (shell thickness approximately 15 nm) prepared in Example 1 was subjected to simulated accelerated UV aging (UVB 0.6 W / m², 72 h), acid rain erosion (pH 4.5, erosion rate 50 mm / h, duration 2 h), and in vitro drug release (pH 7.4, 37 °C) experiments. The specific procedures are as follows:

[0101] 4.1 Simulated UV accelerated aging experiment was conducted in accordance with GB / T 16422.3—2022 "Laboratory Light Source Exposure Test Methods for Plastics Part 3: Fluorescent UV Lamp". The pyrimidine oxime ether aqueous dispersion system prepared in Comparative Example 1 was used as a control example. The experiment used a UVB-313 fluorescent UV lamp tube, with the irradiance set at 0.6 W / m²@ 313 nm. The sample exposure temperature was 40±2℃, and the continuous light exposure was 72 h. After UV irradiation, the residual amount of active ingredients on the leaf surface was measured, and the retention rate was calculated.

[0102] Test results show that the PTB / CNC adhesive pyrimimethoxam dispersant prepared in Example 1 retained 82% of the active ingredient (pyrimimethoxam) after 72 hours of UV irradiation, meeting the acceptance standard of ≥60%; while the pyrimimethoxam aqueous dispersion system in the control example retained only 28% of the active ingredient (pyrimimethoxam) after 72 hours of UV irradiation.

[0103] 4.2 Simulated acid rain erosion experiments were conducted according to the leaf sample treatment and residue determination methods in GB / T 31270.19—2014 "Test Guidelines for Environmental Safety Evaluation of Chemical Pesticides Part 19: Tests on the Effects on Non-Target Plants". Simulated acid rain was prepared according to ASTM E1196—01(2020) "Preparation and Exposure Methods of Artificial Simulated Acid Rain Solutions", and the pH was adjusted to 4.5±0.1 using a sulfuric acid-nitric acid mixture (molar ratio approximately 3:1). Artificial rainfall simulation was used, with a erosion intensity set at 50 mm / h and continuous spraying for 2 h (total erosion volume 100 mm). The pyrimidine oxime-based aqueous dispersion system prepared in Comparative Example 1 was used as a control, and the retention rate of the active ingredient on the leaves was measured after erosion.

[0104] Test results show that the PTB / CNC adhesive pyrimimethoxam dispersant prepared in Example 1, after being washed with acid rain at pH 4.5 for 2 hours, had a foliar active ingredient (pyrimimethoxam) retention rate of 86%, meeting the acceptance standard of ≥70%; while the pyrimimethoxam aqueous dispersion system in the control example, after being washed with acid rain at pH 4.5 for 2 hours, had a foliar active ingredient (pyrimimethoxam) retention rate of only 32%.

[0105] 4.3 In vitro drug release experiments were conducted according to the National Center for Nanoscience and Technology's "Test Method for In Vitro Release Rate of Polymer-Loaded Drug-Coated Nanomicelles" (Dialysis / Centrifugation Method for Detecting In Vitro Release of Polymer-Loaded Drug-Coated Micelles). The dialysis bag method was used, with a molecular weight cutoff of 8000–14000 Da for the dialysis membrane. The release medium was PBS buffer (pH=7.4), the temperature was 37±0.5℃, and the oscillation rate was 100 rpm. Sampling was performed at predetermined time points (intensive sampling in the first 12 hours, with subsequent intervals appropriately extended to 120 hours) to determine the concentration of pyrimidine oxime-methyl in the release medium, and the cumulative release rate was calculated.

[0106] Test results show that the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 releases approximately 25% in the first 12 hours, <60% cumulatively in 72 hours, and approximately 85% cumulatively in 120 hours, meeting the requirements for long-acting release and exhibiting good sustained-release behavior.

[0107] Test Experiment 5

[0108] Following the procedures in Example 1, 6 mL of PTB / CNC adhesive pyrimidine oxime dispersant was prepared, and then 6 mg of organosilicone surfactant was added and stirred until homogeneous to obtain a PTB / CNC adhesive pyrimidine oxime dispersant with a surfactant, wherein the mass percentage of organosilicone surfactant was 0.1 wt%. The prepared PTB / CNC adhesive pyrimidine oxime dispersant with surfactant was then spread on wheat leaves (contact angle approximately 110°), with the PTB / CNC adhesive pyrimidine oxime dispersant without added organosilicone surfactant prepared in Example 1 serving as a control. The specific experimental procedures are as follows:

[0109] Wheat leaves were selected, gently rinsed with deionized water, and dried. Several leaf samples of the same size (2cm × 4cm) were cut and laid flat on a glass slide. The ends of the leaves were fixed with double-sided tape to keep the leaf surface naturally flat. 2μL of the test droplet was taken from each sample (the control example used PTB / CNC adhesive pyrimidine oxime dispersant without added silicone surfactant, and the experimental example used the same dispersant with 0.1wt% silicone surfactant). The dynamic deposition behavior of the two droplets on the wheat leaf surface was recorded according to the method in Experiment 3, and the real-time contact angle was recorded. The spreading diameter was measured to calculate the coverage area.

[0110] Test results show that the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 without the addition of organosilicon surfactant spreads within 5 seconds, and the contact angle drops to 60°; while the PTB / CNC adhesive pyrimidine oxime dispersant with added surfactant spreads completely within 0.2 seconds, and the contact angle drops to 9°. The coverage area is 5 times larger than that of the PTB / CNC adhesive pyrimidine oxime dispersant prepared in Example 1 without the addition of organosilicon surfactant. This indicates that adding a small amount of organic surfactant to the PTB / CNC adhesive drug dispersant can significantly improve the spreading ability.

[0111] Test Experiment 6

[0112] Following the procedures in Example 1, prepare 6 ml of 10 wt% PTB / CNC adhesive pyrimidine oxime dispersant. Transfer 10 μL of this dispersant to deionized water and dilute 1000 times, bringing the volume to 10 mL to obtain a spray solution with an active ingredient concentration of 0.01 wt%. Cut several 2 cm × 4 cm bermudagrass leaf samples according to the method in Experiment 3, and fix them flat on a glass slide with double-sided tape. Use a handheld sprayer to evenly spray the diluted solution from a vertical distance of approximately 30 cm until the leaf surface is completely wetted. Then place the leaves in a fume hood for 30-60 minutes to air dry naturally. Once the solution has completely dried and formed a film, the treatment is complete and can be used for subsequent shear-induced desorption experiments.

[0113] The shear-induced desorption experiment was conducted as follows: a constant shear stress (approximately 50 g / cm³) was applied using a soft-bristled brush dipped in water. 2 The leaf surface was brushed 10 times (corresponding to a shear rate of 1 shear stroke / s). The results showed that after mechanical shear stimulation, the drug residue rate could be reduced to below 3%. This result indicates that the interfacial adhesive layer constructed by PTB / CNC adhesive dispersant has typical shear threshold response behavior—under low shear conditions (rainwater erosion, shear stress <1 g / cm³). 2 It maintains stable anchorage under conditions of high shear (external friction, shear stress > 50 g / cm²) and high shear stress (external friction, shear stress > 50 g / cm²). 2 Adhesion failure and controlled desorption occur under these conditions. This characteristic endows the PTB / CNC adhesive pyrimidine oxime dispersant with a smart response function of "resistant to rain erosion and easily removed by friction", meeting the practical application needs of efficient removal of residues and reduction of environmental exposure risks before crop harvest.

[0114] The intelligent platform-type multifunctional drug dispersants configured in Examples 2-4 were subjected to relevant performance tests according to Test Experiments 1-6 above. The results showed that the performance test results were consistent with those of the PTB / CNC adhesive pyrimidine oxime dispersant configured in Example 1.

[0115] In summary, the intelligent platform-type multifunctional drug dispersant prepared by the method of this invention exhibits excellent leaf wettability, resistance to environmental erosion, intelligent controlled release, super-spreading, and intelligent removal performance, providing a new approach to improve the performance of adhesive pesticide formulations and achieving the purpose of the invention.

[0116] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A smart platform-type multifunctional drug dispersant, characterized in that, The product includes an aqueous solution of an adhesive dispersant and a solid drug. The adhesive dispersant solute in the aqueous solution is a core-shell structured composite material, wherein the core is biodegradable nanoparticles and the shell is a nanofilm formed by the polymerization of amyloid protein aggregates.

2. The intelligent platform-type multifunctional drug dispersant as described in claim 1, characterized in that, The thickness of the nanofilm ranges from 1 to 50 nm, and it is polymerized from amyloid protein aggregates with a particle size of 1 to 10 nm; the particle size of the adhesive dispersant solute ranges from 500 to 900 nm and the mass concentration is 10 to 20 mg / mL.

3. The intelligent platform-type multifunctional drug dispersant as described in claim 1, characterized in that, The biodegradable nanoparticles are one of cellulose nanofibers, cellulose nanocrystals, lithium magnesium silicate nanosheets, and nano-silica particles; the amyloid protein aggregates are formed by the polymerization reaction of one or more of lysozyme, bovine serum albumin, insulin, and α-lactalbumin.

4. The intelligent platform-type multifunctional drug dispersant as described in claim 3, characterized in that, The cellulose nanofibers have a diameter of 4-10 nm, a length of 1-5 μm, and a mass concentration of 0.1-6 mg / mL. The cellulose nanocrystals have a diameter of 4-10 nm, a length of 100-500 nm, and a mass concentration of 1-30 mg / mL. The lithium magnesium silicate nanosheets have a thickness of 1-3 nm, a lateral dimension of 25-50 nm, and a mass concentration of 1-30 mg / mL. The particle size of the nano-silica particles is 20~200nm, and the mass concentration is 1~30mg / mL; The mass concentration of the protein corresponding to the amyloid aggregate is 1~30 mg / mL.

5. The intelligent platform-type multifunctional drug dispersant as described in claim 1, characterized in that, The intelligent platform-type multifunctional drug dispersant also contains a surfactant, with a mass percentage of 0.001~1wt%.

6. The intelligent platform-type multifunctional drug dispersant as described in claim 1, characterized in that, The solid drug is a pesticide, specifically one of pyrimifluoxane, cyhalothrin, hydrofluoric acid ester, and pyraclostrobin, with a mass percentage of 5-20 wt%.

7. A method for preparing a smart platform-type multifunctional drug dispersant as described in any one of claims 1 to 6, characterized in that, The following steps are included: S1: Preparation of aqueous solution of adhesive dispersant Biodegradable nanoparticles were slowly added to a protein aqueous solution and stirred until homogeneous to obtain a suspension. Then, tris(2-carboxyethyl)phosphonic acid hydrochloride aqueous solution was added dropwise to the prepared suspension and stirred for a period of time under certain temperature conditions to obtain an adhesive dispersant aqueous solution. S2: Preparation of intelligent platform-type multifunctional drug dispersants Weigh a certain mass of solid drug and add it to the aqueous solution of the adhesive dispersant prepared in step S1. Stir and mix evenly to obtain a preliminary drug dispersant. Ultrasonically treat the preliminary drug dispersant to obtain a smart platform type multifunctional drug dispersant.

8. The preparation method of the intelligent platform-type multifunctional drug dispersant as described in claim 7, characterized in that, In step S1, the molar concentration of tris(2-carboxyethyl)phosphine hydrochloride in the aqueous solution is 30-50 mmol / L, the pH is 4-5, the reaction temperature is 25-40℃, and the reaction time is 1-24 h.

9. The preparation method of the intelligent platform-type multifunctional drug dispersant as described in claim 7, characterized in that, The specific operation of step S2 is as follows: the preliminary drug dispersion is pulverized using an ultrasonic cell wall disruptor with operating parameters of 20kHz and ultrasonic power density of 300 W / cm³. 2 The total duration is 1-10 minutes.

10. An application of the intelligent platform-type multifunctional drug dispersant as described in any one of claims 1 to 5, characterized in that, Used as a liquid dispersant in nano-pesticides, cosmetics, coatings, oral liquid drugs, and injectable drugs.

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