Nano suspending agent loaded with difenoconazole and preparation method thereof
The one-pot method for preparing mesoporous silica nanoparticles loaded with difenoconazole solves the problems of easy photodegradation and insufficient stability of difenoconazole, achieving efficient pesticide loading and sustained release, simplifying the preparation process, and reducing environmental pollution.
Patent Information
- Application Number
- CN202511108827.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-08
- Publication Date
- 2025-11-25
AI Technical Summary
In existing technologies, difenoconazole pesticides are prone to photodegradation, have insufficient stability and persistence, and traditional preparation methods are complex, making it difficult to achieve efficient pesticide loading and sustained release.
A one-pot method was used to prepare mesoporous silica nanoparticles loaded with difenoconazole. This method combines the preparation of mesoporous silica nanoparticles with the encapsulation of difenoconazole in one process, forming a stable difenoconazole-loaded nano-suspension. The three-dimensional open network structure of mesoporous silica is used to improve drug loading capacity and sustained-release performance.
It improves the stability and duration of action of difenoconazole, reduces the dosage, simplifies the preparation process, achieves slow and sustained drug release, and reduces environmental pollution.
Smart Images
Figure CN121003214A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of pesticide preparation, in particular to a kind of loaded difenoconazole nano-suspension and preparation method thereof. BACKGROUND
[0002] In the past decade, nanotechnology and nanomaterials have been increasingly applied in various aspects of agriculture, including pest control, seed treatment, fertilizer and pesticide delivery, nutrient uptake of crops or vegetables, detection and purification of toxic agricultural chemicals and water, and pollutant remediation. The application of nanomaterials in agriculture has become a hot topic and can effectively solve some difficulties faced by traditional formulations, especially mesoporous silica nanoparticles as a carrier for loading pesticides have become a research hotspot for scholars. Loading pesticides with mesoporous silica nanoparticles not only improves drug solubility and permeability, allowing it to accurately penetrate target plants without dissipating due to external environmental factors such as wind speed and temperature, but also has a sustained-release effect, prolonging drug release time and allowing active ingredients to be released slowly and continuously rather than in short bursts. This not only reduces the frequency of drug administration and saves medication, but also avoids overuse of the drug, which can damage the environment.
[0003] One-pot method is a modified sol-gel method, the biggest advantage of which is that the preparation of mesoporous silica nanoparticles and the encapsulation of active ingredients are combined and completed at the same time, without the need to first prepare mesoporous silica nanoparticle shells and then encapsulate active ingredients by adsorption or other methods. One-pot method makes the preparation process of drug-loaded nanoparticles simpler and more convenient, providing the possibility for industrialization.
[0004] Difenoconazole was developed by Syngenta in 1989 and belongs to the triazole class of pesticides. Difenoconazole is a broad-spectrum fungicide used to control diseases in vegetables, fruits, cereals, and other field crops. It has preventive and curative effects by inhibiting the demethylation process in ergosterol synthesis. Difenoconazole is a light-degradable drug, and the one-pot preparation method simultaneously encapsulates the drug and prepares nanoparticles, which not only shortens the preparation time of drug-loaded nanoparticles but also improves the stability and efficacy of difenoconazole. SUMMARY
[0005] The purpose of the present application is to use mesoporous silica nanoparticles prepared by one-pot method to coat or adsorb difenoconazole, increase its stability and efficacy, and reduce the amount of drug administration, thereby reducing the environmental pollution caused by this pesticide.
[0006] The application provides a preparation method of a nano-suspension agent loaded with difenoconazole.
[0007] The object of the application can be achieved by the following technical solutions.
[0008] The application provides a nano-suspension agent loaded with difenoconazole, and components are shown in the following mass ratio: 1-50% of nano-particles loaded with difenoconazole, 1-10% of wet dispersant, 0.1-5% of thickening agent, 1-5% of antifreezing agent, 0.5-5% of defoaming agent, and the rest is deionized water.
[0009] Further, the preparation of the nano-particles loaded with difenoconazole comprises the following steps:
[0010] (1) preparing an aqueous phase: dissolving cetyltrimethylammonium bromide in pure water, and heating by ultrasonic waves until completely dissolved, and then standing for several minutes until no air bubbles are present on the surface for standby;
[0011] (2) preparing an oil phase: weighing a certain amount of difenoconazole technical material, and dissolving in a beaker for standby;
[0012] (3) transferring the aqueous phase prepared in step (1) into a three-necked flask under mechanical stirring at a certain temperature, and uniformly pouring the oil phase prepared in step (2) into the three-necked flask to form a stable oil-in-water (O / W) emulsion;
[0013] (4) dropping tetraethyl orthosilicate into the three-necked flask at a uniform and slow speed, and then uniformly dropping concentrated ammonia water into the three-necked flask, accelerating the hydrolysis and condensation reaction of tetraethyl orthosilicate and water, so that the solution gradually turns white, and a suspension of mesoporous silica nano-particles is obtained;
[0014] (5) centrifuging the suspension obtained in step (4), washing twice with ethanol, and washing once with water, and then freeze-drying in a freeze dryer for 24 hours to obtain a powder of mesoporous silica nano-particles loaded with difenoconazole.
[0015] Further, the content of difenoconazole in the mesoporous silica nano-particles loaded with difenoconazole is greater than 10%.
[0016] Further, the preparation of the nano-suspension agent loaded with difenoconazole comprises the following steps:
[0017] According to the formula, the nano-particles loaded with difenoconazole, the wet dispersant, the thickening agent, the antifreezing agent, the defoaming agent and water are added into a beaker, sheared by a shearing machine for 10-30 seconds, zirconium oxide beads are added, and then grinding is performed in a sand mill to obtain the nano-suspension agent.
[0018] Further, the wetting dispersant is selected from one or more of sodium lignosulfonate, calcium lignosulfonate, naphthalene sulfonate formaldehyde polymer sodium salt, alkyl naphthalene sulfonate formaldehyde condensate, polycarboxylate, polyoxyethylene polyoxypropylene ether block copolymer, dodecyl polyoxyethylene phosphate.
[0019] Further, the thickening agent is selected from one or more of xanthan gum, magnesium aluminum silicate, methyl cellulose, sodium carboxymethyl cellulose.
[0020] Further, the antifreezing agent is selected from one or more of ethylene glycol, propylene glycol, glycerol, urea.
[0021] Further, the antifoaming agent is selected from one of organic silicon antifoaming agents.
[0022] The present application has the following beneficial effects relative to the prior art:
[0023] The mesoporous silica nanoparticles loaded with difenoconazole are prepared by one-pot method, which has the advantages of simple preparation process, short preparation time, simultaneous drug loading process and preparation process.
[0024] The mesoporous silica nanoparticles have a three-dimensional open network structure and high surface area, showing good adsorption capacity. This special structure allows the mesoporous interior space to accommodate a large number of difenoconazole drug molecules, thereby improving the drug loading capacity and also improving the light stability.
[0025] Due to the special structure of the mesopores, the drug can be continuously and slowly released for a long time, which can avoid frequent use of the drug, reduce the amount of the drug used, and thus achieve the purpose of protecting the environment. BRIEF DESCRIPTION OF DRAWINGS
[0026] Figure 1 is a scanning electron microscope image of the mesoporous silica nanoparticle loaded with difenoconazole of the present application. DETAILED DESCRIPTION
[0027] In order to make the purpose, technical scheme and advantages of the present patent more clear, the present patent will be further described in detail below in combination with specific embodiments. It should be understood that the specific embodiments described herein are part of the embodiments of the present application and are not intended to limit the present application. Unless otherwise specified, the experimental methods of the following examples are conventional methods; unless otherwise specified, the experimental materials and reagents used in the following examples can be obtained by commercial means.
[0028] Preparation of mesoporous silica nanoparticles loaded with difenoconazole
[0029] Example 1: Preparation of mesoporous silica nanoparticles loaded with difenoconazole
[0030] Dissolve 0.1 g of cetyltrimethylammonium bromide in 70 mL of water to obtain an aqueous phase, dissolve 0.1 g of difenoconazole in 20 mL of isopropanol to obtain an oil phase, transfer the aqueous phase into a three-necked flask, pour the oil phase into the three-necked flask at a uniform speed to form a stable oil-in-water (O / W) emulsion, drop 0.5 mL of tetraethyl orthosilicate into the three-necked flask at a uniform and slow speed, then drop 0.5 mL of concentrated ammonia water into the three-necked flask at a uniform speed, react at 25 °C for 2 h to obtain a suspension of mesoporous silica nanoparticles, centrifuge the suspension, wash twice with ethanol and once with water, and then freeze dry in a freeze dryer for 24 h to obtain difenoconazole-loaded mesoporous silica nanoparticle powder.
[0031] Example 2: Preparation of difenoconazole-loaded mesoporous silica nanoparticles
[0032] Dissolve 0.1 g of cetyltrimethylammonium bromide in 70 mL of water to obtain an aqueous phase, dissolve 0.1 g of difenoconazole in 20 mL of isopropanol to obtain an oil phase, transfer the aqueous phase into a three-necked flask, pour the oil phase into the three-necked flask at a uniform speed to form a stable oil-in-water (O / W) emulsion, drop 0.5 mL of tetraethyl orthosilicate into the three-necked flask at a uniform and slow speed, then drop 0.5 mL of concentrated ammonia water into the three-necked flask at a uniform speed, react at 25 °C for 2 h to obtain a suspension of mesoporous silica nanoparticles, centrifuge the suspension, wash twice with ethanol and once with water, and then freeze dry in a freeze dryer for 24 h to obtain difenoconazole-loaded mesoporous silica nanoparticle powder.
[0033] Example 3: Preparation of difenoconazole-loaded mesoporous silica nanoparticles
[0034] Dissolve 0.1 g of cetyltrimethylammonium bromide in 70 mL of water to obtain an aqueous phase, dissolve 0.1 g of difenoconazole in 20 mL of isopropanol to obtain an oil phase, transfer the aqueous phase into a three-necked flask, pour the oil phase into the three-necked flask at a uniform speed to form a stable oil-in-water (O / W) emulsion, drop 0.5 mL of tetraethyl orthosilicate into the three-necked flask at a uniform and slow speed, then drop 0.5 mL of concentrated ammonia water into the three-necked flask at a uniform speed, react at 25 °C for 2 h to obtain a suspension of mesoporous silica nanoparticles, centrifuge the suspension, wash twice with ethanol and once with water, and then freeze dry in a freeze dryer for 24 h to obtain difenoconazole-loaded mesoporous silica nanoparticle powder.
[0035] Example 4: Preparation of difenoconazole-loaded mesoporous silica nanoparticles
[0036] Example 1 : Preparation of Difenoconazole loaded mesoporous silica nanoparticles
[0037] Example 5: Preparation of Difenoconazole loaded mesoporous silica nanoparticles
[0038] Example 1 : Preparation of Difenoconazole loaded mesoporous silica nanoparticles
[0039] The drug loading of difenoconazole loaded mesoporous silica nanoparticles of examples 1-5 is shown in table 1.
[0040] Table 1 : Drug loading of difenoconazole nanoparticles
[0041]
[0042] Example 1 : Preparation of Difenoconazole loaded mesoporous silica nanoparticles
[0043] Example 6: 1.78% Difenoconazole nano suspension
[0044] Difenoconazole loaded nanoparticles 10% (Example 4 nanoparticles), Succinic acid di(2-ethylhexyl) sodium sulfonate 0.5%, Dispersing agent Calcium lignosulfonate 12.5%, Propanol 3%, Silicone antifoam agent DF-2850 1%, Magnesium aluminum silicate 0.06% and Xanthan gum 0.03%, Preservative BIT 200 0.2%, Water q.s. to 100%.
[0045] Example 7: 3.56% Difenoconazole nano suspension
[0046] Difenoconazole loaded nanoparticles 20% (Example 4 nanoparticles), Dispersant calcium lignosulfonate 12.5%, Propylene glycol 6%, Silicone antifoam DF-28 2%, Magnesium aluminium silicate 1.2% and Xanthan gum 0.8%, Preservative BIT 2%, Water q.s. to 100%.
[0047] Example 8: 3.56% Difenoconazole nano suspension
[0048] Difenoconazole loaded nanoparticles 20% (Example 4 nanoparticles), Dispersant calcium lignosulfonate 12.5%, Propylene glycol 6%, Silicone antifoam DF-28 2%, Magnesium aluminium silicate 1.2% and Xanthan gum 0.8%, Preservative BIT 2%, Water q.s. to 100%.
[0049] Example 9: 4.27% Difenoconazole nano suspension
[0050] Difenoconazole loaded nanoparticles 24% (Example 4 nanoparticles), Dispersant calcium lignosulfonate 12.5%, Propylene glycol 6%, Silicone antifoam DF-28 2%, Magnesium aluminium silicate 1.2% and Xanthan gum 0.8%, Preservative BIT 2%, Water q.s. to 100%.
[0051] Example 10: 5.34% Difenoconazole nano suspension
[0052] Difenoconazole loaded nanoparticles 30% (Example 4 nanoparticles), Dispersant Atlox 4913 4%, Wetting agent TXC 2%, Agrimulch 1601 # 2%, Silica 1%, Xanthan gum 0.2%, Magnesium aluminium silicate 0.5%, Propylene glycol 4%, Silicone antifoam 0.2%, Water q.s. to 100%.
[0053] Example 11 : 5.34% Difenoconazole nano suspension
[0054] Difenoconazole loaded nanoparticles 30% (Example 4 nanoparticles), Dispersant calcium lignosulfonate 12.5%, Propylene glycol 4.5%, Silicone antifoam DF-28 5%, Magnesium aluminium silicate 0.6% and Xanthan gum 0.4%, Preservative BIT 200.6%, Water q.s. to 100%.
[0055] Example 12: 7.12% Difenoconazole nano suspension
[0056] Difenoconazole loaded nanoparticles 40% (Example 4 nanoparticles), sodium bis(2- ethylhexyl)sulfosuccinate 1%, dispersant calcium lignosulfonate 5%, ethylene glycol 4%, silicone antifoam DF-2850 5%, magnesium aluminum silicate 0.6% and xanthan gum 0.4%, preservative BIT 200 0.4%, water q.s. to 100%.
[0057] Example 13: 7.12% difenoconazole nano-suspension
[0058] Difenoconazole loaded nanoparticles 40% (Example 4 nanoparticles), sodium bis(2- ethylhexyl)sulfosuccinate 3%, dispersant calcium dodecylbenzenesulfonate 20%, propylene glycol 5%, silicone antifoam DF-2851 5%, magnesium aluminum silicate 0.6% and xanthan gum 0.4%, preservative BIT 200 0.8%, water q.s. to 100%.
[0059] Example 14: 8.9% difenoconazole nano-suspension
[0060] Difenoconazole loaded nanoparticles 50% (Example 4 nanoparticles), sodium bis(2- ethylhexyl)sulfosuccinate 3%, dispersant calcium dodecylbenzenesulfonate 20%, propylene glycol 5%, silicone antifoam DF-2851 5%, magnesium aluminum silicate 0.6% and xanthan gum 0.4%, preservative BIT 200 0.8%, water q.s. to 100%.
[0061] The above described examples only express several embodiments of the present application, which are described in more detail and in more detail, but cannot be understood as limiting the scope of the patent. It should be noted that for those skilled in the art, the above embodiments can be made in several ways, combinations and improvements without departing from the concept of the present patent, which are within the scope of protection of the present patent. Therefore, the scope of protection of the present patent shall be subject to the claims.
Claims
1. A nano-suspension of difenoconazole, characterized in that, The preparation method of the loaded diafenthi-conazole nanoparticle suspension agent is as follows:
2. The preparation method of the loaded diafenthi-conazole nanoparticle suspension agent is as follows: (1) preparing an aqueous phase: dissolving cetyltrimethylammonium bromide in pure water, and heating by ultrasonic waves until completely dissolved, and then standing for several minutes until no bubbles are generated on the surface for standby; (2) preparing an oil phase: dissolving diafenthi-conazole with a solvent in a beaker for standby; (3) The water phase prepared in step (1) is transferred to a three-necked flask under mechanical stirring at a certain temperature, and the oil phase prepared in step (2) is poured into it at a constant speed, (3) forming a stable oil-in-water (O / W) emulsion; (4) dropping tetraethyl orthosilicate into a three-necked flask at a uniform and slow speed, and then dropping concentrated ammonia water into the flask at a uniform speed, accelerating the hydrolysis and condensation reaction of the tetraethyl orthosilicate and water, and making the solution gradually white, so as to obtain a suspension of mesoporous silica nanoparticles; (5) centrifuging the suspension obtained in step (4), washing twice with ethanol, and washing once with water, and then freeze-drying in a freeze dryer for 24 hours to obtain a powder of the loaded diafenthi-conazole mesoporous silica nanoparticle.
3. The loaden mesoporous silica nanoparticle of difenoconazole according to claim 1, characterized in that The content of the diafenthi-conazole is greater than 10%.
4. The preparation method of the loaded diafenthi-conazole nanoparticle suspension agent is as follows: According to the formula, the loaded diafenthi-conazole nanoparticle, the wet dispersant, the thickening agent, the antifreeze agent, the defoaming agent and the deionized water are added into a beaker, and sheared by a shearing machine for 10-30 minutes, and then zirconium oxide beads are added and ground in a sand mill to obtain the nanoparticle suspension agent.
5. The nano-suspension of difenoconazole according to claim 1, wherein The wet dispersant is selected from one or more of sodium lignosulfonate, calcium lignosulfonate, naphthalene sulfonate formaldehyde polymer sodium salt, alkyl naphthalene sulfonate formaldehyde condensate, polycarboxylate, polyoxyethylene polyoxypropylene ether block copolymer and dodecyl polyoxyethylene phosphate.
6. The nano-suspension of difenoconazole according to claim 1, wherein The thickening agent is selected from one or more of xanthan gum, magnesium aluminum silicate, methyl cellulose and sodium carboxymethyl cellulose.
7. The nano-suspension of difenoconazole according to claim 1, wherein The antifreeze agent is selected from one or more of ethylene glycol, propylene glycol, glycerol and urea.
8. The nano-suspension of difenoconazole according to claim 1, wherein the nano-suspension is prepared by the method according to claim 7. The defoaming agent is selected from one kind of organic silicon defoaming agent.