Cyfluthrin microcapsule suspending agent and preparation method thereof
By modifying the flucythion microcapsule suspension with nano-mesoporous silica and coconut oil nanoliposome core-shell structure, the problems of insufficient sustained-release performance and poor stability of traditional pesticide formulations were solved, and an efficient and environmentally friendly sustained-release pesticide effect was achieved.
Patent Information
- Application Number
- CN202511073668.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-08-01
- Publication Date
- 2025-09-12
AI Technical Summary
Traditional pesticide formulations have problems such as insufficient sustained-release performance, poor stability, limitations of carrier materials and low bioavailability. In particular, cypermethrin has poor dispersibility in aqueous solution, and the traditional microcapsule preparation process is not environmentally friendly enough.
A core-shell structure with modified nano-mesoporous silica as the core and coconut oil nanoliposomes as the shell is used to improve the drug loading rate through electrostatic adsorption and hydrophobic rivet effect, and a microcapsule suspension is prepared by interfacial polymerization to form a core-shell structured sustained-release agent.
It significantly improves the drug loading rate, prolongs the duration of drug efficacy, reduces the application frequency, reduces environmental degradation, and achieves a highly efficient and environmentally friendly pesticide slow-release effect.
Smart Images
Figure CN120615929A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of pesticide preparation, in particular to a cyfluthrin microcapsule suspension and a preparation method thereof. Background Art
[0002] As a highly effective, broad-spectrum pyrethroid pesticide, cyfluthrin has important applications in agricultural and public health pest control. However, traditional pesticide formulations (such as emulsifiable concentrates and wettable powders) have significant drawbacks: 1. Inadequate sustained-release performance: Traditional dosage forms often result in rapid release of active ingredients due to a burst-release effect, resulting in a short duration of efficacy and the need for frequent administration, which not only increases costs but also increases the risk of contamination to non-target organisms and the environment.
[0003] 2. Poor stability: Cypermethrin is easily degraded by environmental factors such as light and humidity, and has poor dispersibility in aqueous solutions, resulting in low bioavailability.
[0004] 3. Limitations of carrier materials: Existing sustained-release carriers (such as ordinary polymer microcapsules) are difficult to achieve high drug loading rate, controlled release and biocompatibility, especially for the loading and sustained-release control of hydrophobic original drugs.
[0005] With the advancement of nanotechnology, mesoporous silica materials have shown potential for sustained-release pesticides due to their high specific surface area, adjustable pore structure, and ease of surface modification. However, single mesoporous silica carriers present challenges such as difficulty in precisely controlling drug release rates and insufficient long-term stability. Furthermore, traditional microcapsule preparation processes often rely on organic solvents or complex synthesis steps, resulting in high production costs and limited environmental friendliness.
[0006] In response to the above problems, there is an urgent need to develop a flucythrin preparation with high-efficiency loading, controllable sustained release and good environmental stability. Summary of the Invention
[0007] In view of this, the purpose of the present invention is to propose a flucythrin microcapsule suspension and a preparation method thereof. The present invention designs a modified nano-mesoporous silica-liposome sustained-release agent with a core-shell structure and combines it with an interfacial polymerization method to prepare the microcapsule suspension, aiming to solve the problems of uncontrollable pesticide release, poor stability and low bioavailability in the existing technology, and provide a new solution for efficient and environmentally friendly pesticide formulations.
[0008] Based on the above purpose, the present invention provides a cyfluthrin microcapsule suspension and a preparation method thereof.
[0009] A cyfluthrin microcapsule suspension is composed of the following raw materials in parts by weight: 26-30 parts of active ingredient, 10-14 parts of solvent, 1.8-2.2 parts of oil-soluble monomer, 5-7 parts of emulsifier, 1.8-2.2 parts of dispersant, 0.4-0.6 parts of water-soluble reactive monomer, 0.18-0.22 parts of thickener, 0.18-0.22 parts of preservative, 0.18-0.22 parts of defoaming agent, 3-5 parts of antifreeze, 0.18-0.22 parts of pH adjuster, and 44-45.2 parts of deionized water.
[0010] Preferably, the active ingredients include 24-26 parts by mass of a sustained-release agent and 2-4 parts by mass of cyfluthrin technical.
[0011] Preferably, the sustained-release agent is a core-shell structure with modified nano-mesoporous silica loaded with cyfluthrin as the core and coconut oil nanoliposomes loaded with cyfluthrin as the shell.
[0012] Preferably, the modifier of the modified nano-mesoporous silicon in the modified nano-mesoporous silicon loaded with flucythrin is obtained by mixing 3-aminopropyltriethoxysilane and trimethylchlorosilane in a mass ratio of 1:1, wherein the amino group in 3-aminopropyltriethoxysilane serves as a hydrophilic group, which can make the surface of the mesoporous silicon positively charged, enhance the electrostatic adsorption effect between the surface and the negatively charged pesticide flucythrin, and improve the drug loading rate, while the methyl group introduced by trimethylchlorosilane combines with the hydrophobic structure of flucythrin, such as the benzene ring and the long carbon chain, through hydrophobic interaction to form hydrophobic rivets, thereby adsorbing flucythrin through two sites.
[0013] Preferably, the preparation process of the sustained-release agent is as follows: Step A1. Preparation of core material: Preparation of modified nano-mesoporous silica loaded with cyfluthrin; Step A2. Preparation of Shell Material: Preparation of Coconut Oil Nanoliposomes Loaded with Cyfluthrin; Step A3: Core-shell assembly to obtain a sustained-release agent.
[0014] Preferably, the preparation of the core material in step A1 includes the following process: Step A101. Pretreatment of mesoporous silica: The mesoporous silica material is calcined in a muffle furnace at 500-600°C for 4-6 hours to remove surface impurities and organic matter, thereby improving its purity and activity. After cooling to room temperature, the mesoporous silica is dispersed in ethanol and ultrasonically treated for 30-60 minutes to obtain a uniform dispersion. Step A102. Modification of Mesoporous Silica: A modifier is added to the above dispersion and stirred at 60-80°C for 6-12 hours under nitrogen to allow the modifier to react with the hydroxyl groups on the surface of the mesoporous silica to modify the mesoporous silica. After the reaction, the product is centrifuged and washed 3-5 times with ethanol to remove unreacted modifier. The washed product is dried at 60-80°C for 12-24 hours to obtain modified nano-mesoporous silica. Step A103. Loading of flucythrin: dissolve flucythrin stock in an organic solvent to prepare a flucythrin solution, add nano-modified mesoporous silica to the flucythrin solution, and stir at room temperature for 24-48 hours to allow the flucythrin to be fully adsorbed into the pores of the modified nano-mesoporous silica. Remove the organic solvent by reduced pressure evaporation or centrifugal separation, and dry the product at 40-60°C for 6-12 hours to obtain a core material.
[0015] Preferably, the ratio of the mesoporous silica to the ethanol in step A101 is 5-6 g: 240-280 mL.
[0016] The mass ratio of mesoporous silicon to modifier in the dispersion in step A102 is 6-10:1-1.5.
[0017] The organic solvent in step A103 is any one of acetone, ethanol and toluene, and the concentration of the cyfluthrin solution is 20-30 mg / mL.
[0018] The mass ratio of cyfluthrin to modified nano-mesoporous silica in the cyfluthrin solution in step A103 is 1:3-5.
[0019] Preferably, the preparation process of the shell material in step A2 is as follows: Step A201. Preparation of lipid components: Soy lecithin, cholesterol, coconut oil, and Tween 80 were weighed in a mass ratio of 80 mg: 9 mg: 26 mg: 27.7 mg in a round-bottom flask and 5-10 mL of anhydrous ethanol was added until completely dissolved to obtain a lipid component mixture; Step A202. Dissolving cyfluthrin: Weigh 20 mg of cyfluthrin stock and add it to the lipid component mixture, stir to dissolve the cyfluthrin, and obtain a cyfluthrin lipid mixture; Step A203. The flucythrin lipid mixture was subjected to reduced pressure rotary evaporation at 40°C and 0.08-0.1 MPa to volatilize the ethanol. The flask was then purged with nitrogen to remove residual ethanol. Deionized water was then added and the mixture was oscillated at room temperature to uniformly disperse the system. Finally, the mixture was ultrasonically treated at a power of 200-300 W for 10-15 minutes in an ice bath, with each ultrasonic treatment lasting 3 seconds with an interval of 5 seconds to homogenize the particle size of the system to obtain a shell material.
[0020] Preferably, the process of core-shell assembly in step A3 is as follows: Step A301. Dispersion of the core material: Dispersing the modified nano-mesoporous silica loaded with cyfluthrin in a phosphate buffer solution (PBS, pH 7.4) and performing ultrasonic dispersion treatment to form a uniform core material suspension; Step A302. Core-shell assembly: The coconut oil nanoliposome-loaded cyfluthrin solution was added dropwise to the core material suspension, and a magnetic stirrer was turned on and stirred at a speed of 100-150 rpm for 1-2 hours to allow the liposomes to be wrapped around the modified mesoporous silica surface to form a core-shell structured sustained-release agent, wherein the mass ratio of the coconut oil nanoliposome-loaded cyfluthrin to the core material in the coconut oil nanoliposome-loaded cyfluthrin solution was 2-2.5:1; Step A303. Post-treatment: The mixed solution was allowed to stand at 4°C overnight to make the core-shell structure more stable. The next day, the solution was transferred to a centrifuge tube and centrifuged at 8000-10000 rpm for 15-20 minutes. The supernatant was discarded and the precipitate was washed three times with PBS. After each wash, centrifugation was performed to remove unencapsulated liposomes and other impurities. The washed precipitate was redispersed in an appropriate amount of PBS to obtain the final sustained-release agent with coconut oil nanoliposomes loaded with flucythrin as the shell and modified nano-mesoporous silica loaded with flucythrin as the core.
[0021] Step A202. Preparation of sustained-release agent: The prepared modified nano-mesoporous silica loaded with cyfluthrin and coconut oil nanoliposomes were mixed in a mass ratio of 1:2-3, and stirred at room temperature for 2-4 hours to fully mix the two to obtain a sustained-release agent.
[0022] Preferably, the solvent is 150# aromatic solvent oil.
[0023] Preferably, the oil-soluble monomer is polyisocyanate, and the polyisocyanate is any one of hexamethylene diisocyanate and isophorone diisocyanate.
[0024] Preferably, the emulsifier is fatty alcohol polyoxyethylene ether, and the dispersant is naphthalenesulfonate formaldehyde condensate sulfonate.
[0025] Preferably, the water-soluble reaction monomer is a polyamine, the polyamine is any one of ethylenediamine and hexamethylenediamine, and the thickener is xanthan gum.
[0026] Preferably, the preservative is isothiazolinone, and the defoaming agent is silicone.
[0027] Preferably, the antifreeze agent is ethylene glycol, and the pH adjuster is citric acid monohydrate.
[0028] A method for preparing a cyfluthrin microcapsule suspension, characterized in that it comprises the following steps: Step S1. Preparation of an oil phase: preparing an oil phase using an active ingredient, a solvent, and an oil-soluble monomer; Step S2. Preparation of an aqueous phase: preparing an aqueous phase using an emulsifier, a dispersant, and deionized water; Step S3. Preparation of an emulsion: preparing an emulsion using an oil phase and an aqueous phase; Step S4. Post-processing: solidifying the emulsion, and then using an antifreeze agent, a thickener, a pH regulator, a preservative and a defoaming agent to prepare a cyfluthrin microcapsule suspension.
[0029] Beneficial effects of the present invention: The present invention provides a flucythrin microcapsule suspension and a preparation method thereof. The present invention uses modified nano-mesoporous silica as a core (loaded with flucythrin) and modifies the surface with 3-aminopropyltriethoxysilane and trimethylchlorosilane. Through the dual mechanisms of electrostatic adsorption (interaction between the positive charge of the amino group and the negative charge of the pesticide) and hydrophobic rivet effect (binding of the methyl group to the hydrophobic structure of the pesticide), the drug loading rate is significantly improved while ensuring stable storage of the drug in the pores.
[0030] The outer coconut oil nanoliposome shell of the present invention forms a physical barrier, delaying the drug release rate and achieving sustained release for more than 72 hours. Compared with the burst release effect of traditional preparations (24-hour release rate > 60%), the 24-hour release rate of the preparation of the present invention can be controlled at 30%-40%, significantly extending the duration of drug efficacy, reducing the frequency of application, and alleviating the environmental degradation of cyfluthrin.
[0031] Through material innovation and process optimization, the present invention breaks through the bottlenecks of uncontrollable release and poor stability of traditional pesticide formulations, and has significant application value in the field of efficient, safe and environmentally friendly pesticide formulations. BRIEF DESCRIPTION OF THE DRAWINGS
[0032] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0033] Figure 1 Schematic diagram of the structure of the sustained-release agent prepared in the present invention; Figure 2 TEM image of the sustained-release agent prepared in the present invention; Figure 3 This is the particle size distribution diagram of the sustained-release preparation prepared in the present invention. DETAILED DESCRIPTION
[0034] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to specific embodiments.
[0035] Example 1: Figure 1 As shown, the sustained-release agent prepared by the present invention is a spherical structure with modified nano-mesoporous silica loaded with cyfluthrin as the core layer and coconut oil nano-liposomes loaded with cyfluthrin attached to the surface. The preparation process is as follows: S1. Pretreatment of Mesoporous Silica: The mesoporous silica was calcined in a muffle furnace at 500°C for 4 h to remove surface impurities and organic matter, thereby improving its purity and activity. After cooling to room temperature, the mesoporous silica was dispersed in ethanol and ultrasonicated for 30 min to achieve uniform dispersion. The ratio of mesoporous silica to ethanol was 5 g:240 mL. S2. Modification of mesoporous silica: A modifier was added to the above dispersion and stirred at 60°C for 6 hours under nitrogen to allow the modifier to react with the hydroxyl groups on the surface of the mesoporous silica to modify the mesoporous silica. After the reaction, the product was centrifuged and washed three times with ethanol to remove unreacted modifier. The washed product was dried at 60°C for 12 hours to obtain modified nano-mesoporous silica. The mass ratio of mesoporous silica to modifier in the dispersion was 6:1. S3. Loading of cyfluthrin: Dissolve cyfluthrin stock in acetone to prepare a cyfluthrin solution. Add the nano-modified mesoporous silica to the cyfluthrin solution and stir at room temperature for 24 hours to allow the cyfluthrin to fully adsorb into the pores of the modified nano-mesoporous silica. Remove the acetone by reduced pressure evaporation or centrifugation, and dry the product at 40°C for 6 hours to obtain a core material. The concentration of the cyfluthrin solution is 20 mg / mL, and the mass ratio of cyfluthrin to modified nano-mesoporous silica in the cyfluthrin solution is 1:3. S4. Preparation of lipid components: Soy lecithin, cholesterol, coconut oil, and Tween 80 were weighed in a mass ratio of 80 mg: 9 mg: 26 mg: 27.7 mg in a round-bottom flask, and 5 mL of anhydrous ethanol was added until completely dissolved to obtain a lipid component mixture; S5. Dissolution of cyfluthrin: Weigh 20 mg of cyfluthrin original drug and add it to the lipid component mixture, stir to dissolve the cyfluthrin, and obtain a cyfluthrin lipid mixture; S6. The cyfluthrin-lipid mixture was subjected to reduced pressure rotary evaporation at 40°C and 0.08 MPa to volatilize the ethanol. The flask was then purged with nitrogen to remove residual ethanol. Deionized water was then added and the mixture was shaken at room temperature to uniformly disperse the system. Finally, ultrasonic treatment was performed in an ice bath at a power of 200 W for 10 minutes, with each ultrasonication cycle lasting 3 seconds and an interval of 5 seconds to homogenize the particle size of the system to obtain the shell material. S7. Dispersion of the core material: The modified nano-mesoporous silica loaded with cyfluthrin was dispersed in phosphate buffer solution (PBS, pH 7.4) and subjected to ultrasonic dispersion treatment to form a uniform core material suspension; S8. Core-shell assembly: A solution of cyfluthrin loaded with coconut oil nanoliposomes was added dropwise to the core material suspension while stirring at 100 rpm using a magnetic stirrer for 1 hour to allow the liposomes to wrap around the modified mesoporous silica surface, thereby forming a core-shell structured sustained-release agent. The mass ratio of cyfluthrin loaded with coconut oil nanoliposomes to the core material in the solution was 2:1. S9. Post-treatment: The mixed solution was allowed to stand at 4°C overnight to make the core-shell structure more stable. The next day, the solution was transferred to a centrifuge tube and centrifuged at 8000 rpm for 15 minutes. The supernatant was discarded and the precipitate was washed 3 times with PBS. After each wash, centrifugation was performed to remove unencapsulated liposomes and other impurities. The washed precipitate was redispersed in an appropriate amount of PBS to obtain the final sustained-release agent with coconut oil nanoliposomes loaded with flucythrin as the shell and modified nano-mesoporous silica loaded with flucythrin as the core. The TEM image of the sustained-release agent was measured as shown below. Figure 2 The particle size distribution diagram is shown in Figure 3 As shown; S10. Preparation of the oil phase: 24 g of the sustained-release agent and 2 g of the original cyfluthrin were mixed to obtain the active ingredient, 26 g of the active ingredient, 10 g of 150 # aromatic solvent oil and 1.8 g of polyisocyanate were mixed to obtain an oil phase; S11 Preparation of the aqueous phase: 5g fatty alcohol polyoxyethylene ether, 1.8g naphthalenesulfonate formaldehyde condensate sulfonate and 44g deionized water were mixed to prepare an aqueous phase; S12. Preparation of emulsion: Pour the prepared oil phase into the aqueous phase and homogenize at high speed to form a stable O / W emulsion. The average particle size is measured to be 5 μm. Start stirring and heat the homogenized emulsion to 45°C. Add 0.4 g of polyamine and maintain a stable capsule wall material curing temperature for 4 hours. Finally, add 3 g of ethylene glycol and xanthan gum aqueous solution, adjust the pH to 5.4 with monohydrate citric acid aqueous solution, and finally add 0.18 g of isothiazolinone and 0.18 g of silicone defoaming agent and stir evenly to obtain a flucythrinate microcapsule suspension, wherein the concentration of the xanthan gum aqueous solution is 2%, and the mass of the xanthan gum in the xanthan gum aqueous solution is 0.18 g.
[0036] Example 2: S1. Pretreatment of Mesoporous Silica: The mesoporous silica was calcined in a muffle furnace at 550°C for 5 h to remove surface impurities and organic matter, thereby increasing its purity and activity. After cooling to room temperature, the mesoporous silica was dispersed in ethanol and ultrasonicated for 45 min to achieve uniform dispersion. The ratio of mesoporous silica to ethanol was 5.5 g:260 mL. S2. Modification of mesoporous silica: A modifier was added to the above dispersion and stirred at 70°C for 9 hours under nitrogen to allow the modifier to react with the hydroxyl groups on the surface of the mesoporous silica to modify the mesoporous silica. After the reaction, the product was centrifuged and washed four times with ethanol to remove unreacted modifier. The washed product was dried at 70°C for 18 hours to obtain modified nano-mesoporous silica. The mass ratio of mesoporous silica to modifier in the dispersion was 8:1.2. S3. Loading of cyfluthrin: The cyfluthrin stock was dissolved in ethanol to prepare a cyfluthrin solution. The nano-modified mesoporous silica was added to the cyfluthrin solution and stirred at room temperature for 36 hours to allow the cyfluthrin to be fully adsorbed into the pores of the modified nano-mesoporous silica. The ethanol was removed by reduced pressure evaporation or centrifugation, and the product was dried at 50°C for 9 hours to obtain a core material. The concentration of the cyfluthrin solution was 25 mg / mL, and the mass ratio of cyfluthrin to modified nano-mesoporous silica in the cyfluthrin solution was 1:4. S4. Preparation of lipid components: Soy lecithin: cholesterol: coconut oil: Tween 80 was weighed in a mass ratio of 80 mg: 9 mg: 26 mg: 27.7 mg. Soy lecithin, cholesterol, coconut oil and Tween 80 were placed in a round-bottom flask and 7.5 mL of anhydrous ethanol was added until completely dissolved to obtain a lipid component mixture; S5. Dissolution of cyfluthrin: Weigh 20 mg of cyfluthrin original drug and add it to the lipid component mixture, stir to dissolve the cyfluthrin, and obtain a cyfluthrin lipid mixture; S6. The cyfluthrin-lipid mixture was subjected to reduced pressure rotary evaporation at 40°C and 0.09 MPa to volatilize the ethanol. The flask was then purged with nitrogen to remove residual ethanol. Deionized water was then added and the mixture was shaken at room temperature to uniformly disperse the mixture. Finally, ultrasonic treatment was performed in an ice bath at a power of 250 W for 12.5 minutes, with each ultrasonication lasting 3 seconds with an interval of 5 seconds to homogenize the particle size of the mixture to obtain the shell material. S7. Dispersion of the core material: The modified nano-mesoporous silica loaded with cyfluthrin was dispersed in phosphate buffer solution (PBS, pH 7.4) and subjected to ultrasonic dispersion treatment to form a uniform core material suspension; S8. Core-shell assembly: A solution of cyfluthrin loaded with coconut oil nanoliposomes was added dropwise to the core material suspension while stirring at 125 rpm using a magnetic stirrer for 1.5 h to allow the liposomes to encapsulate the modified mesoporous silica surface, forming a core-shell structured sustained-release agent. The mass ratio of cyfluthrin loaded with coconut oil nanoliposomes to the core material in the solution was 2.2:1. S9. Post-treatment: The mixed solution was allowed to stand at 4°C overnight to stabilize the core-shell structure. The next day, the solution was transferred to a centrifuge tube and centrifuged at 9000 rpm for 17 minutes. The supernatant was discarded, and the precipitate was washed three times with PBS. After each wash, centrifugation was performed to remove unencapsulated liposomes and other impurities. The washed precipitate was redispersed in an appropriate amount of PBS to obtain the final sustained-release agent with coconut oil nanoliposomes loaded with cyfluthrin as the shell and modified nano-mesoporous silica loaded with cyfluthrin as the core. S10 Preparation of the oil phase: 25g of the sustained-release agent and 3g of the original drug of cyfluthrin were mixed to obtain the active ingredient, 28g of the active ingredient, 12g150# aromatic solvent oil and 2g of polyisocyanate were mixed to obtain an oil phase; S11 Preparation of the aqueous phase: 6g fatty alcohol polyoxyethylene ether, 2g naphthalenesulfonate formaldehyde condensate sulfonate and 44.6g deionized water were mixed to prepare an aqueous phase; S12. Preparation of emulsion: Pour the prepared oil phase into the aqueous phase and homogenize at high speed to form a stable O / W emulsion. The average particle size is measured to be 5 μm. Start stirring and heat the homogenized emulsion to 45°C. Add 0.5 g of polyamine and maintain a stable capsule wall material curing temperature for 4 hours. Finally, add 4 g of ethylene glycol and xanthan gum aqueous solution, adjust the pH to 5.4 with citric acid monohydrate aqueous solution, and finally add 0.2 g of isothiazolinone and 0.2 g of silicone defoaming agent and stir evenly to obtain a flucythrinate microcapsule suspension, wherein the concentration of the xanthan gum aqueous solution is 2%, and the mass of the xanthan gum in the xanthan gum aqueous solution is 0.2 g.
[0037] Example 3: S1. Pretreatment of Mesoporous Silica: The mesoporous silica was calcined in a muffle furnace at 600°C for 6 h to remove surface impurities and organic matter, thereby improving its purity and activity. After cooling to room temperature, the mesoporous silica was dispersed in ethanol and ultrasonicated for 60 min to achieve uniform dispersion, resulting in a dispersion solution with a ratio of 6 g mesoporous silica to 280 mL ethanol. S2. Modification of mesoporous silica: A modifier was added to the above dispersion and stirred at 80°C for 12 hours under nitrogen to allow the modifier to react with the hydroxyl groups on the surface of the mesoporous silica to modify the mesoporous silica. After the reaction, the product was centrifuged and washed five times with ethanol to remove unreacted modifier. The washed product was dried at 80°C for 24 hours to obtain modified nano-mesoporous silica. The mass ratio of mesoporous silica to modifier in the dispersion was 10:1.5. S3. Loading of cyfluthrin: The cyfluthrin stock was dissolved in toluene to prepare a cyfluthrin solution. Nano-modified mesoporous silica was added to the cyfluthrin solution and stirred at room temperature for 48 hours to allow the cyfluthrin to be fully adsorbed into the pores of the modified nano-mesoporous silica. The toluene was removed by reduced pressure evaporation or centrifugation, and the product was dried at 60°C for 12 hours to obtain a core material. The concentration of the cyfluthrin solution was 30 mg / mL, and the mass ratio of cyfluthrin to modified nano-mesoporous silica in the cyfluthrin solution was 1:5. S4. Preparation of lipid components: Soy lecithin: cholesterol: coconut oil: Tween 80 was weighed in a mass ratio of 80 mg: 9 mg: 26 mg: 27.7 mg. Soy lecithin, cholesterol, coconut oil and Tween 80 were placed in a round-bottom flask and 10 mL of anhydrous ethanol was added until completely dissolved to obtain a lipid component mixture; S5. Dissolution of cyfluthrin: Weigh 20 mg of cyfluthrin original drug and add it to the lipid component mixture, stir to dissolve the cyfluthrin, and obtain a cyfluthrin lipid mixture; S6. The cyfluthrin-lipid mixture was subjected to reduced pressure rotary evaporation at 40°C and 0.1 MPa to volatilize the ethanol. The flask was then purged with nitrogen to remove residual ethanol. Deionized water was then added and the mixture was shaken at room temperature to uniformly disperse the mixture. Finally, ultrasonic treatment was performed in an ice bath at 300 W for 15 minutes, with each ultrasonication cycle lasting 3 seconds and an interval of 5 seconds, to homogenize the particle size of the system to obtain the shell material. S7. Dispersion of the core material: The modified nano-mesoporous silica loaded with cyfluthrin was dispersed in phosphate buffer solution (PBS, pH 7.4) and subjected to ultrasonic dispersion treatment to form a uniform core material suspension; S8. Core-shell assembly: A solution of cyfluthrin loaded with coconut oil nanoliposomes was added dropwise to the core material suspension while stirring at 150 rpm using a magnetic stirrer for 2 h to allow the liposomes to encapsulate the modified mesoporous silica surface, forming a core-shell structured sustained-release agent. The mass ratio of cyfluthrin loaded with coconut oil nanoliposomes to the core material in the solution was 2.5:1. S9. Post-treatment: The mixed solution was allowed to stand at 4°C overnight to stabilize the core-shell structure. The next day, the solution was transferred to a centrifuge tube and centrifuged at 10,000 rpm for 20 minutes. The supernatant was discarded, and the precipitate was washed three times with PBS. After each wash, centrifugation was performed to remove unencapsulated liposomes and other impurities. The washed precipitate was redispersed in an appropriate amount of PBS to obtain the final sustained-release agent with coconut oil nanoliposomes loaded with cyfluthrin as the shell and modified nano-mesoporous silica loaded with cyfluthrin as the core. S10. Preparation of the oil phase: 26 g of the sustained-release agent and 4 g of the original cyfluthrin were mixed to obtain the active ingredient, 30 g of the active ingredient, 14 g of 150 # aromatic solvent oil and 2.2 g of polyisocyanate were mixed to obtain an oil phase; S11 Preparation of the aqueous phase: 7g fatty alcohol polyoxyethylene ether, 2.2g naphthalenesulfonate formaldehyde condensate sulfonate and 45.2g deionized water were mixed to prepare an aqueous phase; S12. Preparation of emulsion: Pour the prepared oil phase into the aqueous phase and homogenize at high speed to form a stable O / W emulsion. The average particle size is measured to be 5 μm. Start stirring, heat the homogenized emulsion to 45°C, add 0.6 g of polyamine, maintain a stable capsule wall material curing temperature and cure for 4 hours, finally add 5 g of ethylene glycol and xanthan gum aqueous solution, adjust the pH to 5.4 with monohydrate citric acid aqueous solution, finally add 0.22 g of isothiazolinone and 0.22 g of silicone defoaming agent and stir evenly to obtain a flucythrinate microcapsule suspension, wherein the concentration of the xanthan gum aqueous solution is 2%, and the mass of the xanthan gum in the xanthan gum aqueous solution is 0.22 g.
[0038] Comparative Example 1: Compared with Example 1, this comparative example only replaced the "active ingredient" with "an equal amount of sustained-release agent", and the remaining steps and parameters were the same, which will not be repeated in this comparative example. Finally, a cyfluthrin microcapsule suspension was obtained.
[0039] Comparative Example 2: Compared with Example 1, this comparative example only replaced the "active ingredient" with "an equal amount of flucythrin technical", and the remaining steps and parameters were the same, which will not be repeated in this comparative example. Finally, a flucythrin microcapsule suspension was obtained.
[0040] Comparative Example 3: Compared with Example 1, this comparative example only replaced the "sustained-release agent" with an equal total amount of "a mixture of modified nano-mesoporous silica, coconut oil nanoliposomes, and flucythrin technical", and the remaining steps and parameters were the same, which will not be repeated in this comparative example. Finally, a flucythrin microcapsule suspension was obtained.
[0041] Comparative Example 4: Compared with Example 1, this comparative example only replaced "coconut oil nanoliposomes loaded with flucythrin" with "coconut oil nanoliposomes", and the remaining steps and parameters were the same, which will not be repeated in this comparative example. Finally, a flucythrin microcapsule suspension was obtained.
[0042] Comparative Example 5: Compared with Example 1, this comparative example only replaces "modified nano-mesoporous silica loaded with flucythrin" with "modified nano-mesoporous silica", and the remaining steps and parameters are the same, which will not be repeated in this comparative example. Finally, a flucythrin microcapsule suspension is obtained.
[0043] Performance testing: 1. Drug Loading Efficiency Determination: Method: 10 mg of the sample from the Examples / Comparative Examples was added to 5 mL of acetonitrile and ultrasonically extracted for 30 minutes. After centrifugation, the supernatant was collected and the cyfluthrin concentration was determined by high-performance liquid chromatography (HPLC). Chromatographic conditions: C18 column (150 mm × 4.6 mm, 5 μm), mobile phase acetonitrile-water (70:30, v / v), flow rate 1.2 mL / min, detection wavelength 225 nm.
[0044] The calculation formula is: drug loading rate (%) = (pesticide mass in extract / total sample mass) × 100%. The results are shown in Table 1 below: Table 1 Drug loading rate test results Data Analysis: The drug loading rates in Examples 1-3 remained stable at 27.8%-29.2%, significantly higher than those in Comparative Examples 1-5 (15.3%-20.5%). Comparative Example 2 (only the technical drug) achieved a loading rate of only 5.2%, an 82% decrease compared to the Examples. This is likely due to electrostatic attraction between the amino groups (positive charge) on the modified nano-mesoporous silica surface and the negative charge of cyfluthrin. Simultaneously, the methyl groups introduced by trimethylchlorosilane form a hydrophobic rivet effect with the hydrophobic structure of the pesticide (benzene rings and long carbon chains). This dual-site interaction increased drug loading by 2-5 times. In Comparative Example 1, which used only a sustained-release agent (without the technical drug), drug loading relied on passive adsorption within the core-shell structure, lacking direct loading of the technical drug, resulting in a 46% decrease. Comparative Example 2 relied on direct dissolution of the technical drug, without adsorption within the mesoporous silica core and encapsulation within the liposome shell. This resulted in easy precipitation of the technical drug and an extremely low loading rate. Comparative Examples 3-5: The core-shell structure was destroyed (such as mixing unassembled core-shell components, lack of liposome or mesoporous silica modification), the adsorption sites were reduced, and the drug loading rate decreased by 28%-43%.
[0045] 2. Sustained-release performance test (in vitro release): Using the dialysis bag method (molecular weight cut-off 3500Da), 50mg of sample was dispersed in 10mL of PBS buffer (pH 7.4) and incubated at 37°C with constant shaking (100rpm). 1mL of the release solution was collected at 0.5, 1, 2, 4, 8, 12, 24, 48, and 72h. The concentration was determined by HPLC, and the cumulative release rate was calculated. The results are shown in Table 2 below: Table 2 Sustained-release performance (24 / 48 / 72h cumulative release rate) Data Analysis: The cumulative release rate of the embodiment is 33.8%-36.1% in 24 hours, 50.5%-53.4% in 48 hours, and about 70% in 72 hours, showing a sustained and slow release, which is in line with the ideal curve of pesticide sustained-release preparations (the 24-hour release rate of traditional preparations is >60%). In the comparative examples, the 24h release rate was as low as 45.7% (Comparative Example 4) and as high as 72.1% (Comparative Example 2), both significantly higher than those in the examples, with an obvious burst release effect (e.g., the 72h release rate of Comparative Example 2 reached 95.1%, close to that of the free original drug). This may be due to the sustained-release regulation of the mesoporous silica core: the pore size (3-5nm) limits drug diffusion, and the modifier increases the affinity of the inner surface of the pore, delaying the initial release; coupled with the physical barrier of the liposome shell: the coconut oil liposome membrane is about 5-10nm thick, forming a diffusion barrier, further reducing the release rate (Comparative Example 4 lacks the original drug loaded on liposomes, and the release rate is increased by 30%); the core-shell structure requires the drug to first break through the liposome membrane and then diffuse from the mesoporous silica pores. The double resistance reduces the release rate by 40%-60% (compared with Comparative Example 5 without a shell structure).
[0046] 3. Particle size and zeta potential: Dynamic light scattering (DLS) was used to determine the average particle size and distribution (PDI) of the samples in deionized water, and a zeta potential meter was used to determine the surface charge (25°C, pH 7.0).
[0047] Sedimentation experiment: The sedimentation volume ratio of the sample after centrifugation at 5000 rpm for 10 minutes was observed. The results are shown in Table 3 below: Table 3 Summary of dispersion stability test results Data Analysis: The examples exhibited an average particle size of 175-185 nm, a PDI <0.13, and a sedimentation volume ratio <5%, indicating the formation of a stable O / W emulsion (the emulsifier, fatty alcohol polyoxyethylene ether, and the dispersant, naphthalenesulfonate, were combined to reduce the oil-water interfacial tension to 15-20 mN / m). In contrast, the comparative examples exhibited particle sizes increased to 200-300 nm, a PDI >0.25, and a sedimentation volume ratio as high as 35% (Comparative Example 2). This was attributed to the lack of steric protection provided by the core-shell structure (Comparative Examples 1-2), which resulted in hydrophobic aggregation of the original drug; and the absence of a modifier, which exposed hydroxyl groups on the mesoporous silica surface, leading to aggregation through hydrogen bonding between particles (Comparative Example 5). The examples exhibited a stable surface charge of −14 to −16 mV, maintaining dispersibility through electrostatic repulsion. However, the comparative examples exhibited a reduced absolute potential (<−10 mV) due to the lack of components (e.g., the absence of liposomes), resulting in insufficient electrostatic repulsion and prone to particle aggregation.
[0048] 4. Prepare the sample into a 10 mg / L solution and irradiate it under a 250W UV lamp (λ=365nm). Take samples at intervals and determine the residual concentration by HPLC. Calculate the photolysis half-life (t1 / 2). The results are shown in Table 4 below: Table 4 Summary of photostability test results Data Analysis: The photolysis half-life in the examples is 11.8-13.0 hours, six times that of the free original drug (2 hours) and significantly better than the comparative examples (minimum 2.1 hours, maximum 8.8 hours). This is due to the shielding mechanism: the mesoporous silica wall (20-30 nm thick) absorbs 200-400 nm UV light, reducing direct drug exposure; the unsaturated fatty acid structure of the liposome shell captures free radicals and inhibits photooxidation reactions (Comparative Example 2, without protection, has a half-life of only 2.1 hours and a photolysis rate of 99% within 72 hours). In practical applications, extending the photostability period can reduce the frequency of field application (for example, traditional formulations require every three days, while the examples can be extended to seven days), reducing the loss of efficacy due to photodegradation, making it particularly suitable for outdoor crop control.
[0049] 5. Insecticidal activity (targeting corn borer larvae): Using the feed drip method, the sample was prepared into a 200 mg / kg solution and treated with third-instar larvae. The mortality rate was recorded at 24, 48, and 72 hours, and the median lethal dose (LD50) was calculated. The results are shown in Table 5 below: Table 5 Insecticidal activity (lethality at a dose of 200 mg / kg) Data Analysis: Analysis of the difference in lethality showed that at a dose of 200 mg / kg, the lethality of the present invention was over 90% at 24 hours and 100% at 72 hours, significantly higher than that of the control (maximum 95%, minimum 50%). The present invention also maintained a release of over 50% at 48 hours, maintaining the nerve agent (cyfluthrin) to Na + / K + - Sustained inhibition of ATPase (Comparative Example 2, due to a burst release, resulted in an excessively high concentration early on but insufficient concentration later, resulting in a 72-hour lethality rate of only 70%). The surface charge of the core-shell structure (the negatively charged liposome shell) electrostatically attracts the positively charged insect cuticle, increasing attachment to the insect surface (Comparative Example 4, lacking liposomes, saw a 30% reduction in attachment and a 17% decrease in lethality). Comparative Examples 1-2, however, experienced insufficient drug loading or uncontrolled release, resulting in insufficient drug delivery to the target or a short duration of action. Comparative Examples 3-5 experienced core-shell separation or missing components, leading to drug loss or photolysis. For example, in Comparative Example 5, due to the lack of a mesoporous silica core, the photolysis rate increased by 46%, reducing the actual effective dose.
[0050] The cyfluthrin microcapsule suspension and its preparation method provided by the present invention achieve the following significant effects through innovative core-shell structure design and formulation optimization: 1. Highly Efficient Drug Loading and Targeted Sustained-Release Performance: Core-Shell Structure Synergy: Using modified nano-mesoporous silica as the core (loaded with flucythrin), the surface is modified with 3-aminopropyltriethoxysilane and trimethylchlorosilane. Through the dual mechanisms of electrostatic adsorption (interaction between the positive amino group charge and the negative charge of the pesticide) and hydrophobic rivet effect (binding of the methyl group to the hydrophobic structure of the pesticide), this formulation significantly improves drug loading efficiency (by 20%-30% compared to traditional carriers) while ensuring stable drug storage within the pores. Controlled Sustained Release: The outer coconut oil nanoliposome shell forms a physical barrier, slowing the drug release rate and achieving sustained release for over 72 hours. Compared to the burst release effect of traditional formulations (24-hour release rate >60%), the 24-hour release rate of this formulation can be controlled to 30%-40%, significantly extending the duration of drug efficacy and reducing the frequency of application.
[0051] 2. Improved Stability and Environmental Adaptability: Light and Chemical Stability: The silica wall structure of the mesoporous silica core shields against UV light. Combined with the antioxidant properties of the liposome shell, this extends the photolysis half-life of cyfluthrin to 4-8 times that of the free technical drug (e.g., under UV irradiation, the half-life of the free technical drug is 2 hours, while this formulation reaches 8-16 hours), effectively resisting environmental degradation. Optimized Water Dispersibility: By combining emulsifiers such as fatty alcohol polyoxyethylene ethers with a thickener such as xanthan gum, a stable water-based suspension system is formed, eliminating the use of organic solvents. The resulting particles are uniform (100-200 nm) and have a dispersibility exceeding 95%, eliminating the agglomeration problem of the hydrophobic technical drug in water.
[0052] 3. Biocompatibility and Safety: Low-toxicity excipient system: Biocompatible materials such as coconut oil liposomes, a natural thickener (xanthan gum), an environmentally friendly antifreeze (ethylene glycol), and a solvent-free formulation are used to reduce acute toxicity to non-target organisms (such as bees and aquatic organisms). Experimental verification shows that the formulation's cytotoxicity to mammalian cells (IC50 > 200 μg / mL) is significantly lower than that of traditional emulsifiable concentrates (IC50 < 50 μg / mL). Targeted Enrichment and Residue Reduction: The surface charge of the core-shell structure (positively charged core + neutral lipid shell) allows for electrostatic adsorption to bind to insect cuticular proteins, enhancing target site accumulation and reducing soil and water migration. The pesticide residue is expected to be reduced by 30%-50%.
[0053] 4. Simple Preparation Process and Industrial Feasibility: The interfacial polymerization method simplifies the process: through an emulsion curing reaction between the oil phase (active ingredient + solvent + monomer) and the aqueous phase (emulsifier + dispersant), complex nanoassembly equipment is not required. The reaction conditions are mild (room temperature stirring, reduced pressure evaporation), making it suitable for large-scale production and reducing costs by 20%-30% compared to traditional nanoformulations. Parameter Adjustability: By adjusting the modifier ratio (e.g., a 1:1 weight ratio of aminosilane to methylsilane) and the liposome composition (soy lecithin: cholesterol: coconut oil = 80:9:26), the sustained-release rate can be flexibly controlled (fast-release / sustained-release), adapting to different crop or pest control needs.
[0054] 5. Comprehensive Performance Advantages: Enhanced Insecticidal Activity: Compared to the free technical, the microcapsule suspension concentrate (SC) increases the 24-hour mortality rate against pests such as corn borer and German cockroach by 30%-50% (e.g., at a dose of 200 mg / kg, the mortality rate increases from 60% to 90%). This is attributed to its sustained release properties, which allow the drug to exert its effects at the target site. Environmentally Friendly: No organic solvent residue is present, and the amount of defoamer (organic silicone) and preservative (isothiazolinone) used in traditional formulations is reduced to half, complying with the environmental requirements of EU REACH regulations for pesticide formulations.
[0055] In summary, the present invention has broken through the bottlenecks of uncontrollable release and poor stability of traditional pesticide formulations through material innovation and process optimization, and has significant application value in the field of efficient, safe and environmentally friendly pesticide formulations.
[0056] The core-shell structure (modified mesoporous silica core + liposome shell) and the excipient formula (polyisocyanate + polyamine) in this invention form a synergistic system. The absence of any one component leads to performance degradation (as demonstrated in Comparative Examples 3-5, a mixed, rather than assembled, core-shell formulation cannot achieve the same effect). This breakthrough is achieved in four dimensions: drug loading, sustained release, stability, and activity. Compared to traditional formulations (e.g., burst release rate of emulsifiable concentrates >60% and photolysis half-life <3h), the data in the examples all reach industry-leading levels. The low release rate reduces pesticide loss, photostability reduces environmental residues, and dispersion stability reduces the need for adjuvants, aligning with the global trend of reducing pesticide use and increasing its effectiveness.
[0057] Those skilled in the art should understand that the discussion of any of the above embodiments is merely illustrative and is not intended to imply that the scope of the present invention is limited to these examples. Within the scope of the present invention, the technical features in the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and there are many other variations of the different aspects of the present invention as described above, which are not provided in detail for the sake of simplicity.
[0058] The present invention is intended to cover all such substitutions, modifications and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.
Claims
1. A cyfluthrin microcapsule suspension, characterized in that, It is composed of the following raw materials in parts by weight: 26-30 parts of active ingredient, 10-14 parts of solvent, 1.8-2.2 parts of oil-soluble monomer, 5-7 parts of emulsifier, 1.8-2.2 parts of dispersant, 0.4-0.6 parts of water-soluble reactive monomer, 0.18-0.22 parts of thickener, 0.18-0.22 parts of preservative, 0.18-0.22 parts of defoaming agent, 3-5 parts of antifreeze, 0.18-0.22 parts of pH adjuster, and 44-45.2 parts of deionized water.
2. The cyfluthrin microcapsule suspension according to claim 1, wherein The active ingredients include 24-26 parts by mass of a sustained-release agent and 2-4 parts by mass of cyfluthrin technical.
3. The cyfluthrin microcapsule suspension according to claim 2, wherein The sustained-release agent has a core-shell structure with modified nano-mesoporous silica loaded with cyfluthrin as a core and coconut oil nano-liposome loaded with cyfluthrin as a shell.
4. The cyfluthrin microcapsule suspension according to claim 3, wherein The modifier of the modified nano-mesoporous silica in the modified nano-mesoporous silica loaded with cyfluthrin is obtained by mixing 3-aminopropyltriethoxysilane and trimethylchlorosilane in a mass ratio of 1:
1.
5. The cyfluthrin microcapsule suspension according to claim 1, wherein The solvent is 150# aromatic solvent oil, the oil-soluble monomer is polyisocyanate, and the polyisocyanate is any one of hexamethylene diisocyanate and isophorone diisocyanate.
6. The cyfluthrin microcapsule suspension according to claim 1, wherein The emulsifier is fatty alcohol polyoxyethylene ether, and the dispersant is naphthalenesulfonate formaldehyde condensate sulfonate.
7. The cyfluthrin microcapsule suspension according to claim 1, wherein The water-soluble reaction monomer is a polyamine, the polyamine is any one of ethylenediamine and hexamethylenediamine, and the thickener is xanthan gum.
8. The cyfluthrin microcapsule suspension according to claim 1, wherein The preservative is isothiazolinone, and the defoaming agent is silicone.
9. The cyfluthrin microcapsule suspension according to claim 1, wherein The antifreeze agent is ethylene glycol, and the pH regulator is citric acid monohydrate.
10. The method for preparing the cyfluthrin microcapsule suspension according to any one of claims 1 to 9, characterized in that: The following steps are involved: Step S1. Preparation of an oil phase: preparing an oil phase using an active ingredient, a solvent, and an oil-soluble monomer; Step S2. Preparation of an aqueous phase: preparing an aqueous phase using an emulsifier, a dispersant, and deionized water; Step S3. Preparation of an emulsion: preparing an emulsion using an oil phase and an aqueous phase; Step S4. Post-processing: solidifying the emulsion, and then using an antifreeze agent, a thickener, a pH regulator, a preservative and a defoaming agent to prepare a cyfluthrin microcapsule suspension.