A zif drug-loaded nanomaterial, a preparation method and application thereof

Abstract

The application discloses a ZIF drug-loaded nanomaterial, a preparation method and application thereof, and relates to the technical field of pesticide chemistry. A phenolic acid regulator is used for functional modification in the preparation process of ZIF-8 to form a hierarchical porous structure, which is beneficial to improving the drug loading performance of ZIF-8, effectively controlling the release of a pesticide after loading the pesticide, prolonging the persistence of the pesticide, improving the utilization rate of the pesticide, and reducing the amount of the pesticide.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pesticide chemistry, in particular to a ZIF drug-loaded nanomaterial, a preparation method and application thereof. BACKGROUND

[0002] Pesticides are an indispensable part of modern agricultural production practices and play an important role in defending major biological disasters and ensuring food production safety. However, the use of pesticides has also brought many problems. Only 1% of pesticides have effective effects on target organisms, and most pesticides are ultimately lost due to their physicochemical properties, application techniques and environmental factors (such as wind speed, leaching, evaporation, temperature, humidity, sedimentation, photolysis, hydrolysis and microbial activity, etc.), resulting in a large amount of pesticides and pesticide residues distributed in different areas such as soil, air and water. Pesticides can enter contaminated food, be inhaled as dust or aerosol, and humans can directly contact the skin when handling such products, which can enter the human body and cause harm to human health. At the same time, pesticide residues in food reduce the quality of agricultural products and increase the risk of food safety. In addition, long-term use of pesticides can cause biological resistance of pests and pathogenic microorganisms, increasing the difficulty of prevention and control. Therefore, developing new pesticide formulations with good prevention and control effect, low cost, small environmental hazard, and other advantages while having high efficiency, low toxicity and low residue is an effective way to reduce pesticide loss and improve pesticide control effect.

[0003] However, traditional pesticides have the disadvantages of uncontrollable release of active ingredients, short duration, and low water solubility, which not only reduces the prevention and control effect of pesticides, but also causes potential harm to the ecological environment and human and animal health. Therefore, it is urgent to develop a new type of pesticide to improve the utilization rate of pesticides, reduce the amount of pesticides, and achieve pesticide reduction and efficiency, so as to ensure the quality and safety of agricultural products.

[0004] In view of this, the present application is proposed. SUMMARY

[0005] The purpose of the present application is to provide a ZIF drug-loaded nanomaterial, a preparation method and application thereof, which aims to effectively improve the utilization rate of pesticides and reduce the amount of pesticides.

[0006] The present application is realized as follows:

[0007] In a first aspect, the present application provides a ZIF drug-loaded nanomaterial, comprising modified ZIF-8 and a pesticide loaded on the modified ZIF-8.

[0008] The modified ZIF-8 contains a phenolic acid regulator.

[0009] In an optional embodiment, the phenolic acid regulator is selected from at least one of tannic acid, gallic acid, chlorogenic acid and quinic acid.

[0010] Preferably, the phenolic acid regulator is tannic acid.

[0011] In an alternative embodiment, in the modified ZIF-8, the molar ratio of the phenolic acid regulator to 2-methylimidazole is 0.0005-0.0018:1.

[0012] In an alternative embodiment, the pesticide agent is selected from at least one of thiamethoxam and imidacloprid;

[0013] Preferably, the mass ratio of the pesticide agent to the modified ZIF-8 is 16-26:100.

[0014] In a second aspect, the present application provides a method for preparing the ZIF drug-loaded nanomaterial of any one of the preceding embodiments, comprising: using a zinc salt, 2-methylimidazole and a phenolic acid regulator as raw materials to prepare modified ZIF-8, and then loading a pesticide agent on the modified ZIF-8.

[0015] In an alternative embodiment, the molar ratio of zinc ions in the zinc salt to 2-methylimidazole and the phenolic acid regulator is 1:4-12:0.002-0.0216; preferably 1:6-10:0.01-0.015.

[0016] Preferably, the zinc salt is selected from at least one of zinc sulfate, zinc nitrate and zinc acetate.

[0017] In an alternative embodiment, the process for preparing the modified ZIF-8 comprises: dissolving the zinc salt to obtain a zinc salt solution, mixing and dissolving 2-methylimidazole and the phenolic acid regulator to obtain a ligand solution, and mixing and reacting the zinc salt solution and the ligand solution.

[0018] Preferably, the solvent used for preparing the zinc salt solution and the ligand solution is water, and by controlling the total amount of water, the concentration of zinc ions after mixing the zinc salt solution and the ligand solution is 0.05 mol / L-0.25 mol / L.

[0019] Preferably, the reaction temperature is 15℃-30℃, and the reaction time is 3h-6h.

[0020] Preferably, after the reaction is completed, aging treatment is performed for 1h-4h, then the porous ZIF-8 solid is separated, and the porous ZIF-8 solid is washed and dried.

[0021] In an alternative embodiment, the process for loading the pesticide agent on the modified ZIF-8 comprises: mixing and reacting the organic solvent, the pesticide agent and the modified ZIF-8 for 4h-10h.

[0022] Preferably, the mass ratio of the pesticide agent to the modified ZIF-8 added is 2-4:1.

[0023] Preferably, the reaction is carried out under oscillation condition, and the rotation speed is controlled at 700 r / min-1200 r / min.

[0024] Preferably, after the reaction is completed, the drug-loaded particles are separated and dried.

[0025] In an optional embodiment, the organic solvent is selected from at least one of acetone and dichloromethane.

[0026] Preferably, when the pesticide agent is thiamethoxam, the organic solvent used is acetone; when the pesticide agent is imidacloprid, the organic solvent used is dichloromethane.

[0027] Preferably, the amount of the organic solvent is controlled so that the concentration of the pesticide agent in the reaction system is 10 mg / mL-60 mg / mL.

[0028] In a third aspect, the present application provides a pesticide comprising the ZIF drug-loaded nanomaterial of any one of the preceding embodiments or the ZIF drug-loaded nanomaterial prepared by the preparation method of any one of the preceding embodiments.

[0029] The present application has the following beneficial effects: the phenolic acid regulator is used to modify the ZIF-8 in the preparation process to form a hierarchical porous structure, which is beneficial to improve the drug loading performance of the ZIF-8, effectively control the release of the pesticide after loading the pesticide agent, prolong the persistence of the pesticide, improve the utilization rate of the pesticide, and reduce the amount of the pesticide. BRIEF DESCRIPTION OF DRAWINGS

[0030] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiments will be briefly introduced as follows. It should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor.

[0031] Figure 1 SEM images of tannic acid-modified ZIF-8; in the images, (a) represents ZIF-8a(TA30), the amount of tannic acid added is 30 mg; (b) represents ZIF-8a(TA50), the amount of tannic acid added is 50 mg; (c) represents ZIF-8a(TA70), the amount of tannic acid added is 70 mg; (d) represents ZIF-8a(TA100), the amount of tannic acid added is 100 mg, and (e) represents ZIF-8a, without adding tannic acid;

[0032] Figure 2FT-IR spectra of ZIF-8 adjusted by tannic acid; in the figure, a represents ZIF-8a; b represents ZIF-8a (TA30), the amount of tannic acid added is 30 mg; c represents ZIF-8a (TA50), the amount of tannic acid added is 50 mg; d represents ZIF-8a (TA70), the amount of tannic acid added is 70 mg; e represents ZIF-8a (TA100), the amount of tannic acid added is 100 mg;

[0033] Figure 3 XRD spectra of ZIF-8 adjusted by tannic acid; in the figure, (a) represents the standard spectrum of ZIF-8 and the spectra of ZIF-8a, ZIF-8a (TA30); (b) represents the spectra of ZIF-8a (TA50), ZIF-8a (TA70) and ZIF-8a (TA100);

[0034] Figure 4 N2 adsorption-desorption performance and BJH pore size distribution curve of different samples; in the figure, (a) represents the isotherm curve; (b) represents the BJH pore size distribution curve;

[0035] Figure 5 THIA and IMC drug loading rate (%) and encapsulation rate (%) comparison chart of different medicinal materials;

[0036] Figure 6 THIA and IMC release curve under different pH conditions; in the figure, (a) represents THIA, (b) represents IMC;

[0037] Figure 7 Drug-loaded ZIF-8 release performance test result chart; in the figure, (a) represents the performance test result chart of THIA drug-loaded material; (b) represents the performance test result chart of IMC drug-loaded material. DETAILED DESCRIPTION

[0038] In order to make the purpose, technical scheme and advantages of the embodiments of the present application more clear, the technical scheme in the embodiments of the present application will be clearly and completely described below. If the specific conditions are not indicated in the embodiments, the conventional conditions or the conditions suggested by the manufacturer are adopted. If the reagents or instruments used are not indicated by the manufacturer, they are all conventional products that can be purchased in the market.

[0039] The embodiments of the present application provide a preparation method of ZIF drug-loaded nanomaterial, which comprises the following steps:

[0040] S1, preparing modified ZIF-8

[0041] The modified ZIF-8 is prepared by using zinc salt, 2-methyl imidazole and phenolic acid regulator as raw materials, Zn 2+The metal node is 2-methyl imidazole, and the organic ligand is functionalized by phenolic acid regulator competing with 2-methyl imidazole for coordination, so as to control the morphology, mesoporous structure and surface functional parameters of ZIF-8 material, so that the ZIF-8 nano carrier has more binding sites and the performance of the material is improved.

[0042] In some embodiments, the molar ratio of zinc ions in the zinc salt to 2-methyl imidazole and phenolic acid regulator is 1:4-12:0.002-0.0216, preferably 1:6-10:0.01-0.015. By accurately controlling the amount of each raw material, the drug loading performance of the modified ZIF-8 is further improved.

[0043] Further, the zinc salt is selected from at least one of zinc sulfate, zinc nitrate and zinc acetate, and can be any one or several of the above. The phenolic acid regulator is selected from at least one of tannic acid, gallic acid, chlorogenic acid and quinic acid; preferably tannic acid, and the selection of the above several phenolic acid regulators can control the morphology of ZIF-8 and increase the binding sites of the ZIF-8 nano carrier.

[0044] In actual operation, the process for preparing the modified ZIF-8 includes: dissolving the zinc salt to obtain a zinc salt solution, mixing and dissolving 2-methyl imidazole and the phenolic acid regulator to obtain a ligand solution, mixing and reacting the zinc salt solution and the ligand solution, and the reaction can be carried out at 15-30°C (room temperature), and the reaction time can be 3-6h to ensure that the reaction is fully carried out.

[0045] Specifically, the reaction temperature can be 15°C, 20°C, 25°C, 30°C, etc., the reaction time can be 3h, 4h, 5h, 6h, etc., and the reaction process is carried out under magnetic stirring at a stirring rate of 400-500rpm.

[0046] In some embodiments, the solvent used for preparing the zinc salt solution and the ligand solution is water, and by controlling the total amount of water, the concentration of zinc ions after mixing the zinc salt solution and the ligand solution is 0.05-0.25mol / L, such as 0.05mol / L, 0.10mol / L, 0.15mol / L, 0.20mol / L, 0.25mol / L, etc. The amount of water used in the preparation of the zinc salt solution and the ligand solution can be approximately the same.

[0047] In some embodiments, after the reaction is completed, aging treatment is carried out for 1-4h, and then the porous ZIF-8 solid is separated, washed and dried. The aging treatment makes the structure more stable and the combination more compact, and it is not easy to collapse.

[0048] Specifically, the aging treatment is to let the mixture after reaction stand still, and the aging treatment time can be 1 h, 2 h, 3 h, 4 h, etc. The separation means is not limited, and a high-speed centrifuge can be used for centrifugal separation, the rotation speed can be 7000 rpm-9000 rpm, and the centrifugal time can be 5 min-20 min.

[0049] Specifically, the washing can be alternating washing with water and ethanol, and the washing times can be multiple, such as 3 times. The drying can be drying in a freeze dryer.

[0050] S2, drug loading

[0051] The pesticide agent is loaded on the modified ZIF-8, and the pesticide agent is adsorbed on the modified ZIF-8 by a physical adsorption method.

[0052] It should be noted that ZIF-8 is a MOFs material, and the MOFs material has a periodic three-dimensional crystal structure formed by inorganic metal ions or metal clusters and organic ligands through coordination bonds. Due to the change of ligand category or metal coordination value, the structure, surface area and porosity will change, so the modified ZIF-8 has a hierarchical porous structure, which can adsorb pesticide agents to a greater extent.

[0053] In some embodiments, the process of loading pesticide agents on the modified ZIF-8 includes mixing organic solvents, pesticide agents and modified ZIF-8 for 4 h-10 h to fully load the pesticide agents. Specifically, the reaction time can be 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, etc. The pesticide agent can be a neonicotinoid pesticide, such as thiamethoxam, imidacloprid, etc.

[0054] In some embodiments, the mass ratio of pesticide agent to modified ZIF-8 is 2-4:1, such as 2.0:1, 2.5:1, 3.0:1, 3.5:1, 4.0:1, etc. By further controlling the amount of pesticide agent, the loading rate of the agent can be improved.

[0055] Further, the organic solvent is selected from at least one of acetone, dichloromethane, acetonitrile and DMF, and can be any one or several of the above. Preferably, when the pesticide agent is thiamethoxam, the organic solvent used is acetone; when the pesticide agent is imidacloprid, the organic solvent used is dichloromethane. By screening the organic solvent, the drug loading rate is further provided.

[0056] Further, the amount of organic solvent is controlled so that the concentration of the pesticide in the reaction system is 10 mg / mL-60 mg / mL, so that the pesticide is in full contact with the modified ZIF-8. Specifically, the concentration of the pesticide in the reaction system can be 10 mg / mL, 15 mg / mL, 22.5 mg / mL, 30 mg / mL, 45 mg / mL, 60 mg / mL, etc.

[0057] In some embodiments, the reaction process is carried out under oscillation conditions, and the rotation speed is controlled to be 700 r / min-1200 r / min, so that the original pesticide is fully loaded on the carrier material through oscillation.

[0058] In some embodiments, the preparation method further comprises: after the reaction is completed, separating to obtain the pesticide-loaded particles, and drying the pesticide-loaded particles. The separation method is not limited, and the centrifugal separation method can be used, the centrifugal speed can be 8000 r / min-12000 r / min (such as 10000 r / min), and the centrifugation time can be 3 min-8 min (such as 5 min). The drying method is not limited, and the vacuum freeze-drying method can be used for drying.

[0059] The embodiment of the present application also provides a ZIF pesticide-loaded nanomaterial, which comprises modified ZIF-8 and a pesticide loaded on the modified ZIF-8; wherein the modified ZIF-8 contains a phenolic acid regulator. The ZIF pesticide-loaded nanomaterial can improve the utilization rate of the pesticide, reduce the amount of pesticide, avoid the adverse effects of large amounts of pesticide residues on food quality and safety, and has good application prospects in pesticide loading and controlled release.

[0060] In some embodiments, in the modified ZIF-8, the molar ratio of the phenolic acid regulator to 2-methylimidazole is 0.0005-0.0018:1. By controlling the ratio of the phenolic acid regulator to 2-methylimidazole in the material, the drug loading effect of the material can be effectively improved, so that the mass ratio of the pesticide to the modified ZIF-8 in the product is 16-26:100, that is, the mass of the pesticide in 100 g of pure modified ZIF-8 is 16-26 g.

[0061] The embodiment of the present application also provides a pesticide, which comprises the above-mentioned ZIF pesticide-loaded nanomaterial, and can further comprise a reagent for dispersing the ZIF pesticide-loaded nanomaterial. The specific components are not limited, and can be selected according to the application scenario.

[0062] The features and properties of the present application are further described in detail below in combination with embodiments.

[0063] Embodiment 1

[0064] The embodiment provides a preparation method of modified ZIF-8, which comprises the following steps:

[0065] Take 4 mmol of anhydrous zinc sulfate and dissolve it in 20 mL of deionized water to form solution A. Take 32 mmol of 2-methylimidazole and 0.018 mmol (30 mg) of tannic acid, and dissolve them in 20 mL of deionized water to form solution B. Ultrasonically treat solution A and solution B for 3 min, respectively, to form a homogeneous solution.

[0066] After solution B is magnetically stirred at room temperature for 5 min (at a speed of 450 rpm), solution A is immediately added to solution B, which is continuously magnetically stirred at room temperature for 4 h (at a speed of 450 rpm). Then, the obtained solution is aged at room temperature for 2 h. Finally, the hierarchical porous ZIF-8 solid generated in the reaction is separated by using a high-speed centrifuge (at a speed of 8000 rpm for 10 min), and the collected solid is washed with deionized water and ethanol alternately for three times, and dried in a freeze dryer for 24 h (with a cold trap temperature of -80℃ and a sample chamber temperature of 20℃) to obtain ZIF-8a (TA30).

[0067] Example 2

[0068] The difference from Example 1 is that the amount of tannic acid is 0.030 mmol (50 mg), and ZIF-8a (TA50) is obtained.

[0069] Example 3

[0070] The difference from Example 1 is that the amount of tannic acid is 0.042 mmol (70 mg), and ZIF-8a (TA70) is obtained.

[0071] Example 4

[0072] The difference from Example 1 is that the amount of tannic acid is 0.059 mmol (100 mg), and ZIF-8a (TA100) is obtained.

[0073] Example 5

[0074] The present embodiment provides a preparation method of a ZIF drug-loaded nanomaterial, which comprises the following steps:

[0075] (1) Preparation of modified ZIF-8

[0076] The specific steps refer to Example 2, and ZIF-8a (TA50) is obtained.

[0077] (2) Drug loading

[0078] Into a 2 mL centrifuge tube, 1 mL of acetone was added, then 7.5 mg of thiamethoxam (THIA) technical material and 15 mg of ZIF-8a (TA50) were added into the centrifuge tube, sealed and shaken for 6 h at a speed of 1000 r / min, so as to fully load the technical material on the carrier material, then centrifuged at 10000 r / min for 5 min, and the supernatant was poured out, to obtain THIA@ZIF-8 drug-loaded particles, which were vacuum freeze-dried for 12 h.

[0079] Note: In this example, the mass ratio of THIA to ZIF-8a (TA50) is 1:2.

[0080] Examples 6-11

[0081] The difference between this example and Example 5 is only that the amount of thiamethoxam (THIA) is different, and the amount of thiamethoxam (THIA) in Examples 6-11 is 10 mg, 15 mg, 22.5 mg, 30 mg, 45 mg, and 60 mg, respectively.

[0082] Note: In Examples 6-11, the mass ratio of THIA to ZIF-8a (TA50) is 2:3, 1:1, 3:2, 2:1, 3:1, and 4:1, respectively.

[0083] Example 12

[0084] This example provides a preparation method of ZIF drug-loaded nanomaterials, comprising the following steps:

[0085] (1) Preparation of modified ZIF-8

[0086] The specific steps refer to Example 2 to obtain ZIF-8a (TA50).

[0087] (2) Drug loading

[0088] Into a 2 mL centrifuge tube, 1 mL of dichloromethane was added, then 7.5 mg of imidacloprid (IMC) technical material and 15 mg of ZIF-8a (TA50) were added into the centrifuge tube, sealed and shaken for 6 h at a speed of 1000 r / min, so as to fully load the technical material on the carrier material, then centrifuged at 10000 r / min for 5 min, and the supernatant was poured out, to obtain IMC@ZIF-8 drug-loaded particles, which were vacuum freeze-dried for 12 h.

[0089] Note: In this example, the mass ratio of IMC to ZIF-8a (TA50) is 1:2.

[0090] Examples 13-18

[0091] The difference from Example 12 is only that the amount of imidacloprid (IMC) is different, and the amount of imidacloprid (IMC) in Examples 13-18 is 10 mg, 15 mg, 22.5 mg, 30 mg, 45 mg, 60 mg, respectively.

[0092] Note: the mass ratio of IMC to ZIF-8a (TA50) in Examples 13-18 is 2:3, 1:1, 3:2, 2:1, 3:1, 4:1, respectively.

[0093] Example 19

[0094] The difference from Example 12 is only that ZIF-8a (TA50) is replaced by ZIF-8a (TA70), that is, the preparation method of step (1) refers to Example 3.

[0095] Example 20

[0096] The difference from Example 5 is only that tannic acid is replaced by an equal amount of gallic acid.

[0097] Example 21

[0098] The difference from Example 5 is only that tannic acid is replaced by an equal amount of chlorogenic acid.

[0099] Example 23

[0100] The difference from Example 5 is only that tannic acid is replaced by an equal amount of quinic acid.

[0101] Example 24

[0102] The difference from Example 5 is only that the solvent in step (2) is replaced by acetonitrile.

[0103] Comparative Example 1

[0104] The difference from Example 1 is only that tannic acid is not added.

[0105] Test Example 1

[0106] The ZIF-8 material prepared in step (1) of Examples 1-4 and Comparative Example 1 is characterized.

[0107] (1) The SEM images of the modified ZIF-8 prepared in step (1) of Examples 1-4 and Comparative Example 1 are tested, and the results are shown in Figure 1 .

[0108] ZIF-8a is a uniform size multilayer ball flower structure, with a diameter of 50±5.00 μm. By introducing different doses (30 mg, 50 mg, 70 mg, 100 mg) of TA, four kinds of ZIF-8a (ZIF-8a(TA30), ZIF-8a(TA50), ZIF-8a(TA70), ZIF-8a(TA100)) were prepared. The multilayer ball flower structure of ZIF-8a was still retained after the addition of TA, with a large surface area and obvious wrinkle structure, which helps to load more pesticides. Compared with ZIF-8a without TA, the particle size is smaller, with an average particle size of 20 μm, which is due to the addition of TA competing with 2-methylimidazole for coordination, resulting in surface defects. However, since the content of TA is small, the attachment area of small particles is small. With the increase of tannic acid content, small particles gradually increase, increasing the roughness of the material surface, which proves that the addition of TA has an impact on the surface structure of ZIF-8a.

[0109] (2) The FT-IR spectra of the modified ZIF-8 prepared in step (1) of Test Examples 1-4 and Comparative Example 1 are shown in Table 2. Figure 2

[0110] Figure 2 The infrared spectrum of ZIF-8a is basically the same as the infrared spectrum of ZIF-8 in previous research results, which proves the successful preparation of ZIF-8a. The stretching vibration peaks at 3140 cm -1 and 2930 cm -1 are related to the C-H bonds on the imidazole ring and methyl, the peaks at 1600 cm -1 and 680 cm -1 belong to C=N and Zn-N bonds, respectively, and the absorption peaks at 1140 cm -1 and 998 cm -1 are the stretching vibration peaks of C-N bonds, which all prove that Zn 2+ is combined with 2-methylimidazole, and ZIF-8a is successfully synthesized. In addition to the stretching vibration peaks of ZIF-8a observed, the addition of TA also produces some new absorption peaks, which may be due to the exposure of new functional groups. The absorption peak at 1570 cm -1 may be related to the planar vibration of the benzene ring on the aromatic compound TA, and the absorption peak at 3440 cm -1 belongs to the O-H bond, which has obvious changes compared with ZIF-8a. This phenomenon may be due to the presence of a large number of hydroxyl groups in TA. At the same time, it can be seen from the infrared spectrum that the intensity of the absorption peak increases, which may be related to the amount of TA added.

[0111] ​(3) The XRD diffraction spectrum of the modified ZIF-8 prepared in step (1) in Test Examples 1-4 and Comparative Example 1 is shown in Table 2. Figure 3

[0112] CCDC 602542 represents the standard card of ZIF-8. By comparing with the standard card, it is found that the typical characteristic peaks of ZIF-8 appear at 2θ = 7.4°, 10.4°, 12.8°, 17.8°, respectively corresponding to (011), (002), (211), (222) planes, proving the successful synthesis of ZIF-8a, and after TA adjustment, the crystal structure of ZIF-8a is not destroyed, and the crystal type, unit cell shape and atomic position do not change greatly. When the amount of TA introduced is 30 mg, 50 mg, 70 mg, the intensity of the main diffraction peak decreases significantly. This transformation is mainly because the addition of TA effectively changes the crystallization process of ZIF-8, resulting in defects or destruction of the crystal structure of ZIF-8. With the increase of the amount of TA to 100 mg, the intensity of the derived peak increases, indicating that the addition of TA can improve the crystallinity of the material crystal, and at the same time, the high molecular weight TA can not only be used as a structure directing agent, but also as a deprotonating agent, increasing the nucleation rate and crystallinity of ZIF-8. The XRD diffraction spectrum of ZIF-8a and ZIF-8 adjusted by different doses of TA has relatively consistent peak position, sharp peak shape, large peak intensity, and no other redundant impurity peaks, which can be explained that the synthesized material is a nanocarrier material with good crystallinity and no impurities.

[0113] Test Example 2

[0114] The N2 adsorption-desorption isotherm performance and BJH pore size distribution of ZIF-8 prepared in step (1) in Test Examples 1-4 and Comparative Example 1 are shown in Table 2. Figure 4

[0115] Figure 4 ​​The N2 adsorption-desorption isotherms of ZIF-8a and ZIF-8a(TA) are shown in Figure (a). It can be seen from the figure that the N2 adsorption-desorption isotherm of the original ZIF-8a shows a typical I-type isotherm (according to the IUPAC classification) of microporous materials, and the N2 adsorption amount increases at a lower pressure (P / P0<0.1), which indicates that the ZIF-8a mainly exists in a microporous structure (according to the IUPAC definition, the micropore diameter is less than 2 nm, and the mesopore diameter is 2-50 nm), and the BJH average pore diameter of 3.0462 nm also indicates that the pore diameter is small. The N2 adsorption-desorption curve of ZIF-8a(TA) gradually changes to a IV-type isotherm with the increase of the amount of TA added, the N2 adsorption amount sharply increases at a higher pressure (P / P=0.8-1.0), and the hysteresis is small, which indicates that the average pore diameter gradually increases with the increase of the amount of TA added, and the synthesized material mainly exists in a mesoporous structure, but also a small amount of microporous structure. The larger pore diameter helps the occupation of the pesticide molecules and increases the drug loading rate of the pesticide. The specific surface area and pore volume of the material decrease after being adjusted by TA, which may be related to the decrease of the number of microporous structures.

[0116] Test Example 3

[0117] The drug loading rate and encapsulation efficiency of the drug-loaded materials prepared in Test Examples 5-18 were tested, and the results are shown in Table Figure 5

[0118] Test method: The drug loading rate and encapsulation efficiency were determined by ultrasonic dissolution method. 10 mg of dried pesticide drug-loaded particles were weighed and dispersed in methanol, and the volume was made to 8 mL. Ultrasonic was performed for 3 h to make the pesticide in the drug-loaded particles release into the methanol. Centrifugation was performed at 8000 r / min for 10 min, the supernatant was filtered through a 0.22 μm filter membrane, and HPLC detection was performed. The calculation methods of the drug loading rate (%) and the encapsulation efficiency (%) are as follows:

[0119] Drug loading rate (%) = (the mass of the pesticide loaded in the nano-pesticide / the total mass of the nano-pesticide) x 100%;

[0120] Encapsulation efficiency (%) = (the mass of the pesticide loaded in the nano-pesticide / the mass of the nano-carrier material input) x 100%.

[0121] From Figure 5 ​It can be seen that by fixing the mass of nanomaterial ZIF-8a(TA50) as 15 mg, the drug loading rate of ZIF-8a(TA50) to THIA gradually increases as the concentration of pesticide increases from 7.5 mg / mL to 45.0 mg / mL, and the highest drug loading rate is 19.41% when the drug material ratio is 3:1, and the encapsulation rate is 10.81%. When the set drug material ratio is 4:1, that is, the concentration of pesticide increases to 60 mg / mL, the drug loading rate of ZIF-8a(TA50) to THIA shows a downward trend, and the encapsulation rate does not change much. Therefore, the drug material ratio of 3:1 is selected as the loading concentration of THIA.

[0122] From Figure 5 It can be seen that the loading rate of IMC shows an upward trend as the drug material ratio increases. When the concentration reaches 60 mg / mL (the drug material ratio is 4:1), the loading effect of ZIF-8a(TA70) to IMC is the best, which is 30.48%, but the encapsulation rate shows a downward trend, which is 5.71%. This shows that the utilization rate of pesticide is very low, resulting in a large amount of pesticide loss. When the drug material ratio is 3:1, the drug loading rate is 24.47%, and the encapsulation rate is 8.03%, which is better.

[0123] Therefore, in order to ensure the accuracy of subsequent experiments and better investigate the loading performance of nanomaterials to pesticides and the release performance of nano-pesticides, the drug material ratio of 3:1 is selected for subsequent experiments.

[0124] Test Example 4

[0125] The release curves of the drug-loaded materials prepared in Test Examples 10 and 17 at different pH values were tested, and the results are shown in Figure 6

[0126] Test method: In order to explore the in vitro release performance of pesticide molecules in drug-loaded particles, the dialysis bag method was used to determine the release behavior of pesticides. Different pH values of release medium were prepared by using sodium hydroxide solution and hydrochloric acid solution. The release medium was prepared by phosphate buffer solution (PBS), ethanol, and Tween-80, and the specific ratio was PBS:ethanol:Tween-80=70:29.5:0.5 (V / V / V). The specific operation is as follows: 20 mg of pesticide drug-loaded particles were respectively dispersed in 2 mL of release medium with different pH values, and were all transferred into dialysis bags (molecular weight cut-off is 3500D). The dialysis bag was sealed on both sides, and was placed in a stoppered reagent bottle with 200 mL of release medium. The dialysis bag was oscillated at 30°C, 1 mL of release medium was taken at intervals, the concentration of released pesticide was determined, and 1 mL of fresh release medium was added to ensure that the total volume of the system remained unchanged. The cumulative release amount of pesticide was calculated, and the formula is as follows:

[0127] ​

[0128] In the formula, E r Cumulative release rate (%)

[0129] V1: Volume of release medium extracted each time (1 mL)

[0130] V0: Total volume of released medium (202 mL)

[0131] m p The pesticide content of 20mg THIA@ZIF-8a (TA50) or IMC@ZIF-8a (TA70).

[0132] from Figure 6 It can be seen that THIA and IMC can be slowly released under all four pH conditions, and the cumulative release rate can reach more than 75% within 100 hours of continuous release.

[0133] Among them, THIA showed rapid initial release at pH values ​​of 4, 6, and 7.5, with a cumulative release rate exceeding 50% within 5 hours. Compared to acidic conditions, the release was relatively slow under neutral conditions. At pH value of 5, the cumulative release rate increased at a uniform rate, indicating that slow release was more effective. The release amount reached its peak after 100 hours, with cumulative release rates of 92.38% (pH=4), 96.26% (pH=5), 85.87% (pH=6), and 77.45% (pH=7.4).

[0134] Among them, IMC showed better release effect under weak acid (pH=6) conditions, but the release was too fast in the first 5 hours, and the IMC stock was insufficient in the later period, with a cumulative release rate of less than 85%. When the pH value was 5, the release was relatively slow in the early stage, and the release amount increased slowly in the later stage, with a better release effect. Under different pH conditions, the release amount reached the peak after 100 hours, with a cumulative release rate of 83.09% (pH=4), 87.29% (pH=5), 90.93% (pH=6), and 87.44% (pH=7.4).

[0135] The inventors speculate that the rapid release of pesticides in THIA@ZIF-8a (TA50) and IMC@ZIF-8a (TA70) in the early stages is due to the dispersion of the materials, which causes the pesticides on the material surface to be washed away and redissolved in the slow-release medium. Furthermore, the electrostatic interactions, hydrogen bonds, and van der Waals forces between the pesticides and the nanocarriers are broken by external stirring, leading to the rapid release of pesticides. In the later stages, the more stable coordination bonds in the aromatic rings play a major role in preventing the rapid release of pesticides.

[0136] Experimental Example 5

[0137] The efficacy of the drug-loaded materials prepared in Examples 10 and 19 was tested and compared with that of THIA and IMC technical materials. The results are as follows:Figure 7 As shown.

[0138] Test method: The insecticidal performance of the drug-loaded particles is determined by using whitefly adults. The indoor biological test refers to NY / T 1154.14-2008 “Pesticide Indoor Biological Test Guidelines Insecticide Part 14: Leaf Dip Method”. A certain amount of drug-loaded particles is dispersed in 1L releasing solvent and deionized water (water is a control group), a flat-bottomed glass tube with a diameter of 2.2 cm and a height of 8 cm is prepared, about 3 mL of agar solution (concentration of 2%) is dropped into the bottom of the glass tube, and the glass tube is placed in a fume hood until the agar solidifies. Cabbage leaves are trimmed to the appropriate size (to completely cover the agar), immersed in the drug-loaded particle solution for 20 s, and then naturally air-dried with the back facing up. Then, the leaf is placed back up in the glass tube and tightly attached to the agar, the whitefly on the cotton plant is sucked into the glass tube using a worm suction device, and then the other end of the glass tube is sealed with a cotton plug and placed in a rearing room for rearing. The treated test insects are reared and observed under the conditions of a temperature of 26±1℃, a relative humidity of 70±5%, and a light cycle of L:D (light time: dark time) = 16h:8h, and the number of dead and live whiteflies is checked after 24h, 48h and 72h, respectively, and the mortality rate (%) is calculated according to the following formula:

[0139]

[0140] In the formula, P: mortality rate (%);

[0141] K: number of dead insects, unit: head;

[0142] N: total number of insects, unit: head;

[0143] From Figure 7 It can be seen that after the whitefly is fed for 24h, the mortality rate of THIA and IMC raw materials is obviously higher than that of THIA@ZIF-8a (TA50) and IMC@ZIF-8a (TA70), because the drug-loaded particles have a slow-release effect, and the pesticide cannot be completely released, resulting in the death of part of the whitefly. After the whitefly is fed for 48h, the pesticide of THIA@ZIF-8a (TA50) and IMC@ZIF-8a (TA70) is gradually released, so that the mortality rate of the whitefly is close to 100%, at this time, the mortality rate of the pesticide raw material is lower than that of the nano-pesticide, and the toxicity of THIA@ZIF-8a (TA50) and IMC@ZIF-8a (TA70) is 0.25 times and 0.30 times that of THIA raw material and IMC raw material, respectively, because the early pesticide has a higher toxicity, resulting in a higher mortality rate of the whitefly, and the later insufficient amount of the pesticide results in a significantly lower mortality rate of the pesticide raw material than that of the nano-pesticide. It can be seen that the drug-loaded material prepared in the embodiment can realize slow release and also improve the efficacy.

[0144] The above merely describes the preferred embodiments of the present application, and is not used to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A ZIF drug-loaded nanomaterial, characterized in that, Includes modified ZIF-8 and pesticide formulations loaded on said modified ZIF-8; The modified ZIF-8 contains a phenolic acid regulator; The preparation method of ZIF-loaded drug nanomaterials includes: preparing modified ZIF-8 using zinc salt, 2-methylimidazole and the phenolic acid regulator as raw materials, and then loading the pesticide agent onto the modified ZIF-8; The process for preparing the modified ZIF-8 includes: dissolving the zinc salt to obtain a zinc salt solution; dissolving the 2-methylimidazole and the phenolic acid regulator to obtain a ligand solution; and reacting the zinc salt solution and the ligand solution together. The phenolic acid regulator is tannic acid; the zinc salt is zinc sulfate; the molar ratio of zinc ions in the zinc salt to the 2-methylimidazole and the phenolic acid regulator is 1:4-12:0.002-0.0216; the solvent used to prepare both the zinc salt solution and the ligand solution is water, and the concentration of zinc ions after mixing the zinc salt solution and the ligand solution is controlled to be 0.05 mol / L-0.25 mol / L by controlling the total amount of water used; during the preparation of the modified ZIF-8, the reaction temperature is controlled at 15℃-30℃, and the reaction time is 3h-6h; after the reaction is completed, an aging treatment is performed for 1h-4h, and then porous ZIF-8 solid is obtained by separation, washing and drying the porous ZIF-8 solid. The process of loading the pesticide onto the modified ZIF-8 includes: mixing and reacting the organic solvent, the pesticide, and the modified ZIF-8 for 4-10 hours; the pesticide is selected from at least one of thiamethoxam and imidacloprid; the mass ratio of the pesticide to the modified ZIF-8 is 2-4:1; the reaction of loading the pesticide onto the modified ZIF-8 is carried out under oscillation conditions, with the rotation speed controlled at 700-1200 r / min; after the reaction is complete, the pesticide-loaded particles are separated and dried; when the pesticide is thiamethoxam, acetone is used as the organic solvent; when the pesticide is imidacloprid, dichloromethane is used as the organic solvent; the amount of the organic solvent is controlled so that the concentration of the pesticide in the reaction system is 10 mg / mL-60 mg / mL.

2. A method for preparing the ZIF drug-loaded nanomaterial according to claim 1, characterized in that, include: Modified ZIF-8 was prepared using zinc salt, 2-methylimidazole, and the phenolic acid regulator as raw materials, and then the pesticide agent was loaded onto the modified ZIF-8. The process for preparing the modified ZIF-8 includes: dissolving the zinc salt to obtain a zinc salt solution; dissolving the 2-methylimidazole and the phenolic acid regulator to obtain a ligand solution; and reacting the zinc salt solution and the ligand solution together. The phenolic acid regulator is tannic acid; the zinc salt is zinc sulfate; the molar ratio of zinc ions in the zinc salt to the 2-methylimidazole and the phenolic acid regulator is 1:4-12:0.002-0.0216; the solvent used to prepare both the zinc salt solution and the ligand solution is water, and the concentration of zinc ions after mixing the zinc salt solution and the ligand solution is controlled to be 0.05 mol / L-0.25 mol / L by controlling the total amount of water used; during the preparation of the modified ZIF-8, the reaction temperature is controlled at 15℃-30℃, and the reaction time is 3h-6h; after the reaction is completed, an aging treatment is performed for 1h-4h, and then porous ZIF-8 solid is obtained by separation, washing and drying the porous ZIF-8 solid. The process of loading the pesticide onto the modified ZIF-8 includes: mixing and reacting the organic solvent, the pesticide, and the modified ZIF-8 for 4-10 hours; the pesticide is selected from at least one of thiamethoxam and imidacloprid; the mass ratio of the pesticide to the modified ZIF-8 is 2-4:1; the reaction of loading the pesticide onto the modified ZIF-8 is carried out under oscillation conditions, with the rotation speed controlled at 700-1200 r / min; after the reaction is complete, the pesticide-loaded particles are separated and dried; when the pesticide is thiamethoxam, acetone is used as the organic solvent; when the pesticide is imidacloprid, dichloromethane is used as the organic solvent; the amount of the organic solvent is controlled so that the concentration of the pesticide in the reaction system is 10 mg / mL-60 mg / mL.

3. The preparation method according to claim 2, characterized in that, The molar ratio of zinc ions in the zinc salt to the 2-methylimidazole and the phenolic acid regulator is 1:6-10:0.01-0.

015.

4. A pesticide, characterized in that, This includes the ZIF drug-loaded nanomaterials as described in claim 1 or the ZIF drug-loaded nanomaterials prepared by the preparation method described in any one of claims 2-3.

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