Indoxacarb nano controlled release agent

Abstract

The invention relates to the technical field of pesticide preparations, in particular to an indoxacarb nano controlled release agent. The preparation method of the indoxacarb nano controlled-release agent comprises the following steps: preparing modified chitosan, grafting the modified chitosan to the surface of a hollow silicon dioxide carrier, dispersing the modified hollow silicon dioxide into an indoxacarb acetone solution to load a drug, putting drug-loaded microspheres into a chitosan solution, encapsulating, then putting into a copper sulfate solution, and carrying out freeze-drying to obtain the indoxacarb nano controlled-release agent. And centrifuging, separating, washing and drying to obtain the indoxacarb nano controlled release agent. The indoxacarb nano controlled-release agent disclosed by the invention has good leaf surface adhesion and controlled-release performance, and can improve the biological utilization efficiency of pesticides and better realize the insecticidal effect of the indoxacarb nano controlled-release agent.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticide preparations, and in particular to an indoxacarb nano controlled-release agent. Background Art

[0002] Food security and food safety are the basic guarantees for human survival and healthy living. Only by continuously increasing the crop yield of existing arable land can we meet the growing demand for food and agricultural products of the global population. However, as long as there are crops, there will be pests, and pesticides will need to be used for prevention and control. Indoxacarb is an organic compound with the molecular formula C 22 H 17 ClF3N3O7 is a broad-spectrum oxadiazine insecticide that blocks the sodium ion channels in insect nerve cells, causing the nerve cells to lose their function. It has a contact and stomach poisoning effect and can effectively prevent and control various pests on crops such as grain, cotton, fruits, and vegetables.

[0003] In order to reduce the amount of pesticides used and improve the efficacy of pesticides, water-based nanopesticide controlled-release agents with small size and high specific surface area are expected to solve the key problems of traditional pesticide formulations.

[0004] Patent document CN114097774B discloses a method for preparing a mesoporous silica nano-double-layer microsphere controlled-release agent. The mesoporous silica nano-double-layer microsphere controlled-release agent of this invention not only has good biocompatibility and degradability, but also solves the problems of premature drug release and short duration of effect.

[0005] However, traditional controlled-release agents often fail due to problems such as inability to maintain their effect and being easily washed away by rain, thus affecting their insecticidal efficiency. Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a nano controlled-release agent of indoxacarb to solve the problems of the existing controlled-release agents such as short duration and poor adhesion.

[0007] Based on the above purpose, the present invention provides a method for preparing a nano controlled-release agent of indoxacarb, comprising the following steps: S1: Mix chitosan and triethylenetetramine, stir evenly, react at 60-70°C for 20-24 hours, and after the reaction is complete, distill, precipitate, and dry to obtain amino chitosan; S2: dissolving amino chitosan in pyridine, stirring for 2 h, adding 3-(triethoxysilyl)propyl isocyanate, reacting at 60-70 °C for 20-24 h, evaporating, and washing to obtain modified chitosan; S3: The hollow silica particles were dispersed in deionized water and ultrasonicated for 30 min. The modified chitosan was then added and ultrasonically dispersed uniformly. The pH was adjusted to 4-5 and the reaction was carried out at 30-40°C for 20-24 h to obtain a modified hollow silica carrier. S4: The modified hollow silica carrier was dispersed in an indoxacarb acetone solution, and after ultrasonic treatment, the solution was stirred in the dark at room temperature for 48 h, centrifuged, and dried to obtain drug-loaded nanospheres; The modified hollow silica support and the indoxacarb acetone solution in step S4 are used in a ratio of 1-3 g: 100-200 mL; S5: The drug-loaded nanospheres were dispersed in the chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, and washed, and then placed in a copper sulfate solution for reaction for 1-2 h, centrifuged, separated, washed, and freeze-dried to obtain the indoxacarb nano controlled-release agent.

[0008] Preferably, the usage ratio of chitosan, triethylenetetramine and acetone in step S1 is 6-7 g:160-170 mL:150-200 mL.

[0009] Preferably, in step S2, the usage ratio of the amino chitosan, pyridine and 3-(triethoxysilyl)propyl isocyanate is 1.2-1.4 g: 20-30 mL: 0.25-0.3 mL.

[0010] Preferably, the usage ratio of the hollow silica particles, deionized water and modified chitosan in step S3 is 2-4 g:50-100 mL:1-2 g.

[0011] Preferably, the hollow silica particles in step S3 have a particle size of 3-10 μm.

[0012] Preferably, the concentration of the indoxacarb acetone solution in step S4 is 10-15 mg / mL.

[0013] Preferably, the dosage ratio of the drug-loaded nanospheres, chitosan solution, and copper sulfate solution in step S5 is 1-2 g: 100-200 mL: 10 ml.

[0014] Preferably, the concentration of the chitosan solution in step S5 is 5-6 mg / mL.

[0015] Preferably, the concentration of the copper sulfate solution in step S5 is 0.1M.

[0016] Furthermore, the present invention also provides an indoxacarb nano controlled-release agent.

[0017] The beneficial effects of the present invention are as follows: the indoxacarb nano controlled-release agent of the present invention has good leaf adhesion and still has a high adhesion rate after being washed by rainwater, which can reduce shedding caused by natural effects such as rainwater or wind, thereby improving the bioavailability of the pesticide and better achieving its insecticidal effect.

[0018] The indoxacarb nano controlled-release agent of the present invention uses modified chitosan to modify the carrier, which ensures that the nano controlled-release agent has a rapid release ability under a simulated alkaline environment (intestinal alkaline environment), while also ensuring that it will not release suddenly or quickly under a neutral environment, further ensuring that it can release slowly and continuously under normal conditions.

[0019] The indoxacarb nano controlled-release agent of the present invention has good controlled-release performance and can maintain a protective effect for about 14 days. DETAILED DESCRIPTION

[0020] 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.

[0021] Example 1: A method for preparing a nanometer controlled-release agent of indoxacarb, the specific steps are as follows: (1) 6 g of chitosan and 160 mL of triethylenetetramine were mixed and stirred evenly. The mixture was reacted at 60 °C for 20 h. After the reaction was completed, the solvent was vacuum distilled and the resulting solid was dissolved in deionized water. The solid was then added dropwise to 150 mL of acetone. The reaction was repeated three times and precipitated. The resulting precipitate was dried in a vacuum oven at 40 °C for 2 d to obtain amino chitosan. (2) 1.2 g of amino-modified chitosan was dissolved in 20 mL of pyridine and stirred for 2 h. 0.25 mL of 3-(triethoxysilyl)propyl isocyanate was added and reacted at 60 °C for 20 h. The solvent was removed by vacuum evaporation and the residue was washed three times with n-hexane to obtain modified chitosan. (3) 2 g of hollow silica particles were dispersed in 50 mL of deionized water and ultrasonicated for 30 min. Then, 1 g of modified chitosan was added and ultrasonically dispersed uniformly. The pH was adjusted to 4 and the mixture was reacted at 30 °C for 20 h to obtain a modified hollow silica carrier. (4) 1 g of the modified hollow silica carrier was dispersed in 100 mL of a 10 mg / mL indoxacarb acetone solution. After ultrasonic treatment, the mixture was stirred in the dark at room temperature for 48 h, then centrifuged at 10,000 rpm for 10 min, and dried at 60 °C to obtain drug-loaded nanospheres. (5) Disperse 1 g of drug-loaded nanospheres in 100 mL of 5 mg / mL chitosan solution, stir at room temperature for 15 min, centrifuge, separate, and wash. Then, place it in 10 mL of 0.1 M copper sulfate solution to react for 1 h, centrifuge, separate, wash, and freeze-dry to obtain indoxacarb nano controlled-release agent.

[0022] Example 2: A method for preparing a nanometer controlled-release agent of indoxacarb, the specific steps are as follows: (1) 6.5 g of chitosan and 165 mL of triethylenetetramine were mixed and stirred evenly. The mixture was reacted at 65 °C for 21 h. After the reaction was completed, the solvent was vacuum distilled and the resulting solid was dissolved in deionized water. The solid was then added dropwise to 180 mL of acetone. The reaction was repeated three times and precipitated. The resulting precipitate was dried in a vacuum oven at 40 °C for 2 days to obtain amino chitosan. (2) 1.3 g of amino chitosan was dissolved in 25 mL of pyridine and stirred for 2 h. 0.28 mL of 3-(triethoxysilyl)propyl isocyanate was added and reacted at 65 °C for 22 h. The solvent was removed by vacuum evaporation and the residue was washed three times with n-hexane to obtain modified chitosan. (3) 3 g of hollow silica particles were dispersed in 80 mL of deionized water and ultrasonicated for 30 min. Then, 1.5 g of modified chitosan was added and ultrasonically dispersed uniformly. The pH was adjusted to 5 and the mixture was reacted at 35 °C for 21 h to obtain a modified hollow silica carrier. (4) 2 g of the modified hollow silica carrier was dispersed in 150 mL of a 13 mg / mL indoxacarb acetone solution. After ultrasonic treatment, the mixture was stirred in the dark at room temperature for 48 h, then centrifuged at 10,000 rpm for 10 min, and dried at 60 °C to obtain drug-loaded nanospheres. (5) 1.5 g of drug-loaded nanospheres were dispersed in 150 mL of 5.5 mg / mL chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, and washed. They were then placed in 10 mL of 0.1 M copper sulfate solution for 2 h, centrifuged, separated, washed, and freeze-dried to obtain indoxacarb nano controlled-release agent.

[0023] Example 3: A method for preparing a nanometer controlled-release agent of indoxacarb, the specific steps are as follows (1) 7 g of chitosan and 170 mL of triethylenetetramine were mixed and stirred evenly. The mixture was reacted at 70 °C for 24 h. After the reaction was completed, the solvent was vacuum distilled and the resulting solid was dissolved in deionized water. The solid was then added dropwise to 200 mL of acetone. The reaction was repeated three times and precipitated. The resulting precipitate was dried in a vacuum oven at 40 °C for 2 days to obtain amino chitosan. (2) 1.4 g of amino chitosan was dissolved in 30 mL of pyridine and stirred for 2 h. 0.3 mL of 3-(triethoxysilyl)propyl isocyanate was added and reacted at 70 °C for 24 h. The solvent was removed by vacuum evaporation and the residue was washed three times with n-hexane to obtain modified chitosan. (3) 4 g of hollow silica particles were dispersed in 100 mL of deionized water and ultrasonicated for 30 min. Then, 2 g of modified chitosan was added and ultrasonically dispersed uniformly. The pH was adjusted to 5 and the mixture was reacted at 40 °C for 24 h to obtain a modified hollow silica carrier. (4) 3 g of the modified hollow silica carrier was dispersed in 200 mL of a 15 mg / mL indoxacarb acetone solution. After ultrasonic treatment, the mixture was stirred in the dark at room temperature for 48 h, then centrifuged at 10,000 rpm for 10 min, and dried at 60 °C to obtain drug-loaded nanospheres. (5) 2 g of drug-loaded nanospheres were dispersed in 200 mL of 6 mg / mL chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, washed, and then placed in 10 mL of 0.1 M copper sulfate solution for reaction for 1 h. The solution was centrifuged, separated, washed, and freeze-dried to obtain indoxacarb nano controlled-release agent.

[0024] Comparative Example 1: The difference from Example 2 is that triethylenetetramine is replaced with 1,4-diaminobutane. The specific steps are as follows: (1) 6.5 g of chitosan and 165 mL of 1,4-diaminobutane were mixed and stirred evenly. The mixture was reacted at 65 °C for 21 h. After the reaction was completed, the solvent was vacuum distilled and the resulting solid was dissolved in deionized water. The solid was then added dropwise to 180 mL of acetone. The reaction was repeated three times and precipitated. The resulting precipitate was dried in a vacuum oven at 40 °C for 2 days to obtain amino chitosan. (2) 1.3 g of amino chitosan was dissolved in 25 mL of pyridine and stirred for 2 h. 0.28 mL of 3-(triethoxysilyl)propyl isocyanate was added and reacted at 65 °C for 22 h. The solvent was removed by vacuum evaporation and the residue was washed three times with n-hexane to obtain modified chitosan. (3) 3 g of hollow silica particles were dispersed in 80 mL of deionized water and ultrasonicated for 30 min. Then, 1.5 g of modified chitosan was added and ultrasonically dispersed uniformly. The pH was adjusted to 5 and the mixture was reacted at 35 °C for 21 h to obtain a modified hollow silica carrier. (4) 2 g of the modified hollow silica carrier was dispersed in 150 mL of a 13 mg / mL indoxacarb acetone solution. After ultrasonic treatment, the mixture was stirred in the dark at room temperature for 48 h, then centrifuged at 10,000 rpm for 10 min, and dried at 60 °C to obtain drug-loaded nanospheres. (5) 1.5 g of drug-loaded nanospheres were dispersed in 150 mL of 5.5 mg / mL chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, and washed. They were then placed in 10 mL of 0.1 M copper sulfate solution for 2 h, centrifuged, separated, washed, and freeze-dried to obtain indoxacarb nano controlled-release agent.

[0025] Comparative Example 2: A method for preparing a nanometer controlled-release agent of indoxacarb, the specific steps are as follows: (1) 1.3 g of chitosan was dissolved in 25 mL of pyridine and stirred for 2 h. 0.28 mL of 3-(triethoxysilyl)propyl isocyanate was added and reacted at 65 °C for 22 h. The solvent was removed by vacuum evaporation and the residue was washed three times with n-hexane to obtain modified chitosan. (2) 3 g of hollow silica particles were dispersed in 80 mL of deionized water and ultrasonicated for 30 min. Then, 1.5 g of modified chitosan was added and ultrasonically dispersed uniformly. The pH was adjusted to 5 and the mixture was reacted at 35 °C for 21 h to obtain a modified hollow silica carrier. (3) 2 g of the modified hollow silica carrier was dispersed in 150 mL of a 13 mg / mL indoxacarb acetone solution. After ultrasonic treatment, the mixture was stirred in the dark at room temperature for 48 h, then centrifuged at 10,000 rpm for 10 min, and dried at 60 °C to obtain drug-loaded nanospheres. (5) 1.5 g of drug-loaded nanospheres were dispersed in 150 mL of 5.5 mg / mL chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, and washed. They were then placed in 10 mL of 0.1 M copper sulfate solution for 2 h, centrifuged, separated, washed, and freeze-dried to obtain indoxacarb nano controlled-release agent.

[0026] Comparative Example 3: A method for preparing a nanometer controlled-release agent of indoxacarb, the specific steps are as follows: (1) 2 g of hollow silica carrier was dispersed in 150 mL of 13 mg / mL indoxacarb acetone solution, and after ultrasonic treatment, it was stirred in the dark at room temperature for 48 h, then centrifuged at 10,000 rpm for 10 min, and dried at 60 °C to obtain drug-loaded nanospheres; (2) 1.5 g of drug-loaded nanospheres were dispersed in 150 mL of 5.5 mg / mL chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, and washed. They were then placed in 10 mL of 0.1 M copper sulfate solution for 2 h, centrifuged, separated, washed, and freeze-dried to obtain indoxacarb nano controlled-release agent.

[0027] Performance Testing Leaf retention test: Dry leaves were cut into 2 × 2 cm samples, immersed in the sample solution (200 μg / mL) for 15 seconds, and then lifted vertically with tweezers. After draining, the leaves were weighed and the liquid retention was calculated. Each experiment was repeated three times. The test results are shown in Table 1. Simulated rain shower test: The suspensions obtained in the examples and comparative examples (1 mL, 0.5 mg / mL) were evenly sprayed onto the leaves using a sprayer. The leaves were then rinsed with 50 mL of deionized water to simulate rain (at an angle of 60°, a flushing height of 10 cm, and a flushing rate of 0.2 mL / s). Fluorescence imaging was used to evaluate the retention of the carriers on the cucumber leaves. All experiments were repeated three times in parallel. The test results are shown in Table 1. Release performance test: 5 mg of the samples obtained in Example 2 and the comparative example were dispersed in pH = 7.0 (phosphate buffer) or pH = 9.0 (carbonate buffer), respectively, and placed in dialysis bags. The dialysis bags were then immersed in 200 mL of the corresponding pH buffer and shaken in a constant temperature shaker in the dark. At preset time points (0, 4, 8, 12, 24, and 48 h), 1 mL of the external buffer was removed and an equal volume of fresh buffer was added. The absorbance was measured using a UV spectrophotometer, and the indoxacarb concentration was calculated. The test results are shown in Table 2. Insecticidal tests: A 30 mg / mL suspension of the samples obtained in Example 2 and the comparative example was prepared. Fresh cabbage pieces of the same size were then immersed in the suspension for 10 minutes, removed, and air-dried. Subsequently, 100 cotton bollworms (third-instar larvae) were placed in a Petri dish containing the treated leaves. The dishes were incubated in an incubator (25°C, 70% relative humidity, 16:8 light-dark cycle) for 14 days. The mortality of the cotton bollworms in each dish was monitored. Each experiment was repeated three times. The test results are shown in Table 3.

[0028]

[0029] Data analysis shows that the indoxacarb nano controlled-release agent of the present invention has good leaf adhesion and still has a high adhesion rate after being washed by rain. When used, it can reduce the shedding caused by natural effects such as rain or wind, and better achieve its insecticidal effect. It can be seen from Example 2 and the comparative example that the present invention uses modified chitosan to modify the carrier surface. On the one hand, it can improve the roughness of the surface of the nano controlled-release agent, and then it can cooperate with the villi structure on the surface of the plant leaf surface. On the other hand, the modified chitosan The surface of chitosan has a large number of polar groups, which can form a large number of hydrogen bonds with the yellow on the leaf surface. The combined effect enables the nano controlled release agent to better adhere to the surface of crop leaves. The strong leaf adhesion ability can reduce the shedding of nano pesticides from the leaves, thereby improving the bioavailability of pesticides. From Example 2 and Comparative Example 1, it can be seen that the adhesion performance of chitosan modified with triethylenetetramine is better than that of chitosan modified with 1,4-diaminobutane. This may be because triethylenetetramine has more active sites and can increase the overall amount of hydrogen bonds formed.

[0030]

[0031] As can be seen from Example 2 and the comparative example in Table 2, the present invention uses modified chitosan to modify the carrier, which ensures that the nano controlled-release agent has a rapid release ability under a simulated alkaline environment (intestinal alkaline environment), while also ensuring that it will not have sudden release and rapid release in a neutral environment, further ensuring that it can be slowly and continuously released under normal conditions, and can be quickly released in the alkaline environment of the pest intestine; and Example 2 and the controlled-release performance are better than the comparative example, which is mainly because, on the one hand, the modified chitosan grafted on the carrier surface has good compatibility with the chitosan coated on the carrier surface, which can enhance the coating layer. Thickness and density. On the other hand, a large number of polar groups on the surface of the modified chitosan can form hydrogen bonds with the chitosan coating layer, thereby improving the overall density and stability of the carrier. At the same time, the modified chitosan can exist as a large group, thereby blocking a part of the drug release pores, thereby ensuring that it will not release suddenly or quickly under a neutral environment. It can be seen from Example 2 and Comparative Example 1 that the sustained-release performance of chitosan modified with triethylenetetramine is better than that of chitosan modified with 1,4-diaminobutane. This may be because triethylenetetramine has more active sites and can increase the number of hydrogen bonds.

[0032]

[0033] It can be seen from Example 2 and the comparative example in Table 3 that the nano controlled-release agent of the present invention has good controlled-release performance and can maintain the protective effect for about 14 days.

[0034] 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.

Claims

1. A method for preparing an indoxacarb nano controlled-release agent, characterized in that: The following steps are involved: S1: Mix chitosan and triethylenetetramine, stir evenly, react at 60-70°C for 20-24 hours, and after the reaction is complete, distill, precipitate, and dry to obtain amino chitosan; S2: dissolving amino chitosan in pyridine, stirring for 2 h, adding 3-(triethoxysilyl)propyl isocyanate, reacting at 60-70 °C for 20-24 h, evaporating, and washing to obtain modified chitosan; S3: The hollow silica particles were dispersed in deionized water and ultrasonicated for 30 min. The modified chitosan was then added and ultrasonically dispersed uniformly. The pH was adjusted to 4-5 and the reaction was carried out at 30-40°C for 20-24 h to obtain a modified hollow silica carrier. S4: The modified hollow silica carrier was dispersed in an indoxacarb acetone solution, and after ultrasonic treatment, the solution was stirred in the dark at room temperature for 48 h, centrifuged, and dried to obtain drug-loaded nanospheres; The modified hollow silica support and the indoxacarb acetone solution in step S4 are used in a ratio of 1-3 g: 100-200 mL; S5: The drug-loaded nanospheres were dispersed in the chitosan solution, stirred at room temperature for 15 min, centrifuged, separated, and washed, and then placed in a copper sulfate solution for reaction for 1-2 h, centrifuged, separated, washed, and freeze-dried to obtain the indoxacarb nano controlled-release agent.

2. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, wherein: The usage ratio of chitosan, triethylenetetramine and acetone in step S1 is 6-7 g:160-170 mL:150-200 mL.

3. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, wherein: In step S2, the usage ratio of the amino chitosan, pyridine and 3-(triethoxysilyl)propyl isocyanate is 1.2-1.4 g: 20-30 mL: 0.25-0.3 mL.

4. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, wherein: The usage ratio of the hollow silica particles, deionized water and modified chitosan in step S3 is 2-4 g:50-100 mL:1-2 g.

5. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, wherein: The hollow silica particles in step S3 have a particle size of 3-10 μm.

6. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, characterized in that: The concentration of the indoxacarb acetone solution in step S4 is 10-15 mg / mL.

7. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, characterized in that: The dosage ratio of the drug-loaded nanoparticles, chitosan solution, and copper sulfate solution in step S5 is 1-2 g: 100-200 mL: 10 ml.

8. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, characterized in that: The concentration of the chitosan solution in step S5 is 5-6 mg / mL.

9. The method for preparing the indoxacarb nano controlled-release agent according to claim 1, wherein: The concentration of the copper sulfate solution in step S5 is 0.1M.

10. An indoxacarb nano controlled-release agent, characterized in that: The indoxacarb nano controlled-release agent is prepared according to the preparation method of any one of claims 1 to 9.

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