A suspension formulation of ivermectin and a method of preparing the same

Abstract

The present application relates to a kind of suspension formulation of ivermectin and preparation method thereof, including effective component 1.5%~40%, synergistic adjuvant composition 2%~10%, other adjuvant 0.1%~45%, with water to 100%.Wherein, the effective component is ivermectin and component M, component M is chlorfenapyr or spirotetramat, and the mass ratio is 1:1~1:20;The synergistic adjuvant composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, and the mass ratio of the two is 1:10~7.5:1.Compared with prior art, the present application can alleviate the problem of reduced heat storage suspension rate caused by adding isomeric alcohol polyoxyethylene ether to ivermectin suspension formulation, improve the control effect on phytophagous mites and lepidoptera pests, and meet the practical needs of processing, storage, safety and field application.

Description

Technical Field

[0001] This invention relates to the field of pesticide formulation technology, specifically to an ivermectin suspension formulation and its preparation method. Background Technology

[0002] Ivermectin is a semi-synthetic macrocycline-based biological pesticide, produced by the hydrogenation reduction of metabolites from *Streptomyces avermitilis*. It exhibits high activity against agricultural pests such as mites and lepidopteran insects, and is characterized by high efficiency, low toxicity, environmental friendliness, rapid onset of action, and short residual effect. Meanwhile, chlorfenapyr, a pyrrole-based chemical pesticide, shows good control effects against agricultural pests such as mites, nematodes, and lepidopteran insects, demonstrating a longer residual effect in field applications. Spirotetramat, a quaternary ketoacid compound, possesses unique bidirectional systemic properties, exhibiting a relatively long onset time and field residual effect.

[0003] Chinese patent application CN200510132849.5 discloses a pesticide composition of ivermectin and chlorfenapyr and its field use for killing mites; Chinese patent application CN201910645619.0 discloses a pesticide composition of ivermectin and spirotetramat and its use for controlling pear psyllids and mites. Existing patents only address formulation of compound compositions of pesticide active ingredients. The formulation examples mentioned do not focus on synergistic development for control efficacy. In practical applications, the stability, spreadability, penetration, and control efficacy of ivermectin suspensions with chlorfenapyr or spirotetramat need further improvement. There is an urgent need to develop more stable and efficient suspension formulations to meet the practical needs of processing, storage, safety, and field application. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide an ivermectin suspension formulation and its preparation method. This invention utilizes a specific synergistic adjuvant composition to obtain a stable suspension system. This formulation exhibits good thermal storage stability and enhances the control efficacy of the active ingredient against mites and lepidopteran pests, meeting practical needs in processing, storage, safety, and field application.

[0005] To achieve this objective, the present invention adopts the following technical solution:

[0006] A suspension formulation of ivermectin, comprising, by weight percentage: 1.5%–35% active ingredient, 2%–10% synergistic adjuvant composition, 0.1%–45% other adjuvants, and water to a final volume of 100%. The active ingredient is ivermectin and component M, wherein component M is chlorfenapyr or spirotetramat, with a mass ratio of 1:1 to 1:20; the synergistic adjuvant composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, with a mass ratio of 1:10 to 5:1.

[0007] Preferably, the suspending agent comprises the following components: 20%~35% active ingredient, 3%~6% synergistic adjuvant composition, 0.1%~20% other adjuvants, and water to make up to 100%. The active ingredient is ivermectin and component M, where component M is chlorfenapyr or spirotetramat, and the mass ratio of the two is 1:15~1:20.

[0008] Furthermore, the synergistic adjuvant composition is an isomeric alcohol polyoxyethylene ether and a fatty amine polyoxyethylene ether, with a mass ratio of 1:2 to 5:1. In the suspension of the present invention, the adjuvants used are conventional adjuvants and formulation auxiliary components required for the formulation of pesticides, including one or more of wetting agents, thickeners, antifreeze agents, and defoamers.

[0009] Specifically, the wetting agent is selected from one or more of EO / PO block polyether, alkyl naphthalene sulfonate, fatty alcohol polyoxyethylene ether salt, condensed naphthalene sulfonate, and acyl glutamate;

[0010] Specifically, the thickener is selected from one or more of xanthan gum, carboxymethyl cellulose, gelatin, gum arabic, polyvinylpyrrolidone, carboxyethyl cellulose, methyl cellulose, magnesium aluminum silicate, and polyvinyl alcohol;

[0011] Specifically, the defoamer is selected from one or more of the following: sucrose fatty acid esters, organosilicon compounds, fatty acids, mineral oils, and alcohols.

[0012] Specifically, the antifreeze is selected from one or more of ethylene glycol, glycerol, propylene glycol, polyethylene glycol, sorbitol, or urea.

[0013] The application of the above-mentioned auxiliary materials is to achieve the stability of the physical properties of the formulation and to achieve the desired effect in the field. For the types, functions, and application techniques of the auxiliary materials, please refer to Zhang Xiaojun, Liu Guangwen, et al. ["Pesticide Adjuvants", (2018, Chemical Industry Press).]

[0014] In the synergistic additive composition of the suspending agent of the present invention, the molecular formula of the isomeric alcohol polyoxyethylene ether is RO(CH2CH2O). n H, where R = C10 or C13, n = 5~12.

[0015] Preferably, the molecular formula of the isomeric alcohol polyoxyethylene ether is RO(CH2CH2O). n H, where R=C13, n=5~8.

[0016] The suspending agent of the present invention contains a synergistic additive composition, wherein the fatty amine polyoxyethylene ether has the structural formula of compound (Ⅰ), wherein R = C10, C12 or C18, and n+m = 5~15.

[0017] Equation (I)

[0018] Preferably, the fatty amine polyoxyethylene ether has the structural formula of compound (Ⅰ), wherein R=C18 and n+m=10~15.

[0019] The suspension formulation of this invention can be used to control phytophagous mites, lepidopteran pests, hemiptera pests, and tsanoptera pests on agricultural crops. The phytophagous mites include *Tetranychus maculatus*, *Tetranychus cinnabarinus*, *Tetranychus two-spotted*, *Tetranychus hawthornensis*, etc. The lepidopteran pests include diamondback moth, beet armyworm, cotton bollworm, fall armyworm, and two-spotted armyworm, etc. The hemiptera pests include *Aphidius gracilis*, *Aphidius gracilis*, *Aphidius gracilis*, *Aphidius gracilis*, planthopper, whitefly, scale insects, etc. The tsanoptera pests include melon thrips, onion thrips, rice thrips, and western flower thrips, etc.

[0020] The crops mentioned include food crops, cash crops, fruit trees, vegetables, and medicinal crops. Food crops include corn, rice, wheat, sorghum, etc.; cash crops include peanuts, cotton, rapeseed, sesame, tea, alfalfa, etc.; fruit trees include citrus, apples, pears, kiwifruit, hawthorn, etc.; vegetables include eggplant, tomato and other solanaceous crops, cucumber, early melon, zucchini and other cucurbitaceous crops, cabbage, bok choy and other cruciferous crops; and medicinal crops include ginseng, wolfberry, astragalus, etc.

[0021] Pesticide suspensions are made by processing water-insoluble solid active ingredients of pesticides into fine particles (generally with an average particle size of <5μm), which are then suspended in water under the steric hindrance effect or charge action of surfactants, forming a relatively stable suspension system. Specifically, because pesticide suspensions are highly dispersed, multiphase, and complex systems, their stability is related to many factors. Besides the physicochemical properties of the pesticide active ingredients themselves (such as form, melting point, solubility, chemical stability, light stability, and thermal stability), the compatibility of adjuvants (such as wetting agents, dispersants, antifreeze agents, thickeners, preservatives, defoamers, and other adjuvants) must also be considered, as their interactions will affect the stability of the suspension.

[0022] With the increasing severity of resistance accumulation to pesticide active ingredients and the diversification and complexity of pests, diseases, and weeds in the field, the demand for effective pesticide products is correspondingly increasing. Pesticide adjuvants can, to some extent, improve the wettability, spreadability, penetration, and adhesion of pesticide formulations on plant surfaces, increasing the contact area between pesticides and target organisms or crops, reducing the escape rate of target organisms, and expanding the range of protection for crops. This, in turn, improves the utilization rate of pesticide active ingredients and enhances crop control efficacy.

[0023] Adjuvants such as isomeric alcohol polyoxyethylene ethers exhibit synergistic effects in some suspension concentrate systems, enhancing the spreading, wetting, and penetration properties of active ingredients and improving pesticide efficacy. However, in practical applications, the introduction of single adjuvants like isomeric alcohol polyoxyethylene ethers into compound suspension concentrates of ivermectin and chlorfenapyr, or ivermectin and spirotetramat, negatively impacts the original adjuvant dispersion system, significantly reducing stability. Specifically, this manifests as a substantial decrease in the suspension rate of ivermectin after heat storage, leading to issues such as water separation, paste formation, or decreased stability after dilution, resulting in reduced marketability or shortened shelf life. Therefore, the addition of synergistic adjuvants often places high demands on the adjuvant dispersion system of suspension concentrate products. In conclusion, the permeability, stability, and efficacy of ivermectin suspension concentrates require further improvement.

[0024] The inventors of this application have discovered that simultaneously introducing fatty alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers as additives in the additive composition can better solve the above problems, thereby obtaining a suspension formulation with good stability, dispersion and suspension performance and penetration performance. In particular, when using octadecylamine polyoxyethylene ethers with a higher degree of polymerization, the overall performance of the formulation is better.

[0025] Compared with existing ivermectin suspension formulations, the advantages of this invention are:

[0026] 1) Enhanced stability: This adjuvant composition improves the permeability of the formulation while enhancing the dispersion stability, thermal storage stability, and long-term stability of ivermectin suspension products.

[0027] 2) Significant synergistic effect: The combination of ivermectin and chlorfenapyr, or ivermectin and spirotetramat chlorfenapyr, has high activity against hemiptera, phytophagous mites and lepidopteran pests. On this basis, the application of the synergistic adjuvant composition to the pesticide composition significantly improves the control effect.

[0028] 3) Crop safety: This adjuvant composition effectively reduces the risk of phytotoxicity caused by synergistic adjuvants, and ensures the safety of crop leaves, stems and fruits while improving the control effect. Detailed Implementation

[0029] To better understand the essence of this invention, the following embodiments further illustrate the content of this invention, but these should not be considered as limitations on the invention. The content mentioned in the embodiments is not intended to limit the invention, and the selection of material formulations can be adapted to local conditions without substantially affecting the results. Unless otherwise stated, all percentages below are weight percentages.

[0030] Test Example 1: Suspension Additive Category Test

[0031] 1. Experimental Objective

[0032] Based on the different properties and functions of the tested additives, compliance selection was carried out for different categories of additives, including isomeric alcohol polyoxyethylene ethers, fatty amine polyoxyethylene ethers, phosphate salts, sulfate salts, sulfonates, naphthalene sulfonates, and polycarboxylates. Appropriate additives were combined into 10 composite formulations and 4 single-use formulations, and tests were conducted using a repeatability testing method.

[0033] 2. Test methods

[0034] Weigh each component according to the following mass percentages (see Table 3 for specific composition and dosage): Pesticide active ingredient 1 (ivermectin) content is 1.7%, active ingredient 2 (chlorfenapyr) content is 33.3%; total amount of adjuvant composition (components A and B) is 3-4%; total amount of wetting agent (sulfonate, phosphate ester or polyether) is 1%; total amount of antifreeze (ethylene glycol) is 3%; total amount of defoamer (SAG-1522 (Momentive)) is 0.3%; total amount of thickener (magnesium aluminum silicate) is 0.5%; the remaining amount is made up with deionized water, with a total weight of 100 g. The suspension preparation method is as follows: Add pesticide active ingredients 1 and 2, adjuvant composition, wetting agent, antifreeze, defoamer, thickener, and water to a sand mill, grind, cool, and filter to obtain the suspension.

[0035] Thermal storage stability test: In accordance with GB / T 19136-2021, the sample was placed at 54±2℃ for 14 days to test the appearance of the preparation, the mass fraction of active ingredients and the suspension rate.

[0036] Penetration and wettability test: Referring to GB / T 11983-2008, prepare a diluent solution by diluting the auxiliary agent composition (components A and B, specific composition and content are shown in Table 3) at the same dilution factor, and bring the volume to 1000 mL. Assemble and adjust the position of the sliding bracket of the three-pronged arm on the upper plane of the immersion clamp so that the original cotton cloth disc held by it is about 40 mm below the liquid surface. Pour the test solution into the measuring beaker, remove the foam on the liquid surface, clamp the original cotton cloth disc with the immersion clamp, and immerse it in the solution. Start timing when the lower end of the cloth disc touches the solution, and stop timing when the cloth disc begins to sink automatically. The time interval between the two is recorded as the wetting time.

[0037] The specific evaluation criteria are shown in Tables 1 and 2.

[0038] Table 1. Grading Standards for Thermal Storage Stability (54 °C for 14 days)

[0039]

[0040] Table 2 Wetting and Permeability Classification Standards

[0041]

[0042] The above experiment was repeated, with the content of pesticide active ingredient 1 (ivermectin) being 2% and the content of active ingredient 2 (spirotetramat) being 30%, and the rest being the same.

[0043] 3. Experimental Design and Results

[0044] Taking ivermectin and chlorfenapyr suspensions as an example, the experimental design is as follows:

[0045] Table 3. Adjuvant components and dosages in the formulation examples

[0046]

[0047] Table 3 shows the formulation compatibility of different types of adjuvant compositions with this suspension, as shown in Table 4.

[0048] Table 4 Formulation compatibility of different categories of adjuvant compositions

[0049]

[0050]

[0051] As shown in the table, Examples 1-6 used different types of single adjuvants. When using single adjuvants such as sodium dioctyl sulfonate, organosilicon, or isomeric alcohol polyoxyethylene ether, the suspension exhibited good permeability, but suffered from poor thermal storage stability. Based on this, Examples 7-12 used a combination of isomeric alcohol polyoxyethylene ether or fatty amine polyoxyethylene ether as adjuvants. In Example 9, the addition of a combination of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether significantly improved the thermal storage stability and permeability of the formulation. Specifically, the suspension rate of the active ingredient was 90-95% in terms of thermal storage stability, and the wetting time was 50-60 seconds in terms of permeability. Furthermore, similar tests were conducted with several other adjuvants or combinations of adjuvants; only Examples 13-14 are listed in the table, and no superior combination has yet been obtained.

[0052] The following are some results from suspension formulations of ivermectin and spirotetramat:

[0053] Table 5 Formulation compatibility of different categories of adjuvant compositions

[0054]

[0055] Similarly, in the suspensions of ivermectin and spirotetramat, Examples 15, 17, and 18 used single adjuvants such as sodium dioctyl sulfonate, organosilicon, or isomeric alcohol polyoxyethylene ether, which resulted in better permeability of the suspensions but poor thermal storage stability. In Example 19, a combination adjuvant of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether was added. Compared with the other adjuvant compositions in Examples 20-21, this significantly improved the thermal storage stability and permeability of the formulation. Specifically, the suspension rate of the active ingredient was 90-95% in terms of thermal storage stability, and the wetting time was 50-60 seconds in terms of permeability.

[0056] In summary, when preparing suspensions of ivermectin and chlorfenapyr, or suspensions of ivermectin and spirotetramat, the adjuvant composition of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether exhibits better formulation compatibility. Specifically, it demonstrates good thermal storage stability and superior permeability, meaning that the active ingredient in this formulation can be stably suspended in the diluted solution, exhibiting good dispersion and suspension properties. This facilitates its diffusion and penetration on the plant surface, thereby enhancing the efficacy of the formulation. It can be further screened as a synergistic adjuvant composition.

[0057] Test Example 2: Proportion Test of Additive Composition

[0058] 1. Experimental Objective

[0059] Based on the different properties and functions of the additives, isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers were used as components A and B of the additive composition, and combined in different proportions and applied to the formulation to screen suitable proportions of synergistic additive compositions.

[0060] 2. Test methods

[0061] Weigh each component according to the following mass percentages: pesticide active ingredient 1 (ivermectin) content is 1.7%, active ingredient 2 (chlorfenapyr) content is 33.3%; total amount of synergist composition (component A is isomeric alcohol polyoxyethylene ether, component B is fatty amine polyoxyethylene ether, specific ratio is shown in Table 6) is 3%; total amount of wetting agent (naphthalene sulfonate condensate) is 1%; total amount of antifreeze agent (ethylene glycol) is 3%; total amount of defoamer (SAG-1522 (Momentive)) is 0.3%; total amount of thickener (magnesium aluminum silicate) is 0.5%; the remaining amount is made up with deionized water, with a total weight of 100 g.

[0062] The preparation method of the suspension, the determination of thermal storage stability, and the testing method of wettability and permeability are the same as those in Test Example 1.

[0063] The above experiment was repeated, with the content of pesticide active ingredient 1 (ivermectin) being 2% and the content of active ingredient 2 (spirotetramat) being 30%, and the rest being the same.

[0064] 3. Experimental Design and Results

[0065] Table 6 Formulation compatibility of different proportions of additive compositions

[0066]

[0067] As shown in the table, taking ivermectin and chlorfenapyr suspensions as examples, when the adjuvant compositions of isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers were applied to ivermectin suspension products in Examples 9 and 22-29, the thermal storage stability was significantly better than other ratios when the ratio of component A:B was 1:10 to 5:1; and the penetration performance was significantly better than other ratios when the ratio of component A:B was 1:2 to 5:1, with a wetting time of less than 60 seconds.

[0068] When the above ratio was applied to ivermectin and spirotetramat suspensions, similar results were obtained. When the ratio of adjuvant component A:B was 1:10 to 5:1, the permeability was also excellent. Preferably, A:B = 1:2 to 5:1.

[0069] In summary, when preparing suspensions of ivermectin and chlorfenapyr, or suspensions of ivermectin and spirotetramat, the combination of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether as synergistic additives in a mass ratio of 1:10 to 5:1 exhibits superior thermal storage stability and permeability. Furthermore, when the mass ratio is 1:2 to 5:1, the thermal storage stability and permeability of the product are better than other ratios, showing a significant performance improvement.

[0070] Test Example 3: Test on the Types of Additive Compositions

[0071] 1. Experimental Objective

[0072] Based on the different properties and functions of the tested additives, isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers with different structural types were used as components A and B of the additive composition to screen suitable types of synergistic additive compositions.

[0073] 2. Test methods

[0074] Weigh each component according to the following mass percentages: pesticide active ingredient 1 (ivermectin) content is 1.7%, active ingredient 2 (chlorfenapyr) content is 33.3%; synergistic adjuvant composition (component A is 1%, component B is 2%, see Table 7 for specific structural composition); wetting agent (naphthalene sulfonate condensate) total is 1%; antifreeze agent (ethylene glycol) total is 3%; defoamer (SAG-1522 (Momentive)) total is 0.3%; thickener (magnesium aluminum silicate) total is 0.5%; the remaining amount is made up with deionized water, with a total weight of 100 g.

[0075] The preparation method of the suspension, the determination of thermal storage stability, and the testing method of wettability and permeability are the same as those in Test Example 1.

[0076] The above experiment was repeated, with the content of pesticide active ingredient 1 (ivermectin) being 2% and the content of active ingredient 2 (spirotetramat) being 30%, and the rest being the same.

[0077] 3. Experimental Design and Results

[0078] Isomeric alcohol polyoxyethylene ether is used as component A, with the chemical formula RO(CH2CH2O)nH, and fatty amine polyoxyethylene ether is used as component B, with the chemical structure shown in the figure. Auxiliary components with different chemical structures are selected and applied to the formulation, as detailed in Table 6.

[0079]

[0080] Table 7 Formulation compatibility of additive compositions with different chemical structures

[0081]

[0082]

[0083] As shown in the table, taking the suspension concentrates of ivermectin and chlorfenapyr as examples, the thermal storage stability and permeability of Examples 30-43 are superior to other types of adjuvant combinations, which confirms that when isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers are used as synergistic adjuvants, they are well-suited to ivermectin suspension concentrate products. Component A is isomeric alcohol polyoxyethylene ether RO(CH2CH2O)nH, R=C10 or C13, n=5-10; component B is fatty amine polyoxyethylene ether, R=C10, C12 or C18, n+m=5-15, and its formulation compatibility is superior.

[0084] Furthermore, the formulation compatibility of some combinations is better than that of other synergistic adjuvant compositions. In Examples 30-35, when R=C13 for component A and R=C18 for component B, the thermal storage stability is superior (Example 35). Specifically, in Examples 35-43, when n=5, 6, or 8 for component A and n+m=10 or 15 for component B (specifically Examples 35-36, 38-39, and 42-43), the thermal storage stability and permeability are superior. In particular, in this application, when component A is selected from TO-5, TO-6, or TO-8 and component B is selected from NE-1810 or NE-1815, the dispersibility, thermal storage stability, and permeability of the suspending agent are excellent.

[0085] Furthermore, when the preferred adjuvant formulation is applied to the suspension of ivermectin and spirotetramat, the suspension exhibits excellent dispersibility, thermal stability, and permeability.

[0086] Test Example 4: Suspension Formulation Test of Ivermectin and Chlorfenapyr

[0087] 1. Experimental Objective

[0088] Based on the different properties and functions of the tested additives, different proportions of active ingredients, different contents of active ingredients, different structural types of additive compositions, and other additives were applied to the formulation to screen and obtain a stable formulation.

[0089] 2. Test methods

[0090] Weigh each component according to the following mass percentages (see Table 8 for specific composition and dosage): pesticide active ingredient 1 (ivermectin), active ingredient 2 (chlorfenapyr); synergist composition (components A and B); wetting agent; antifreeze (ethylene glycol) total 3%; defoamer (SAG-1522 (Momentive)) total 0.3%; thickener (magnesium aluminum silicate) total 0.5%; the remaining amount is made up with deionized water, for a total weight of 100 g.

[0091] The preparation method of the suspending agent and the method for determining its thermal storage stability are the same as those in Test Example 1.

[0092] 3. Test Results

[0093] Table 8 Composition and dosage of formulation examples

[0094]

[0095] According to the HG / T2467.5-2003 pesticide suspension concentrate product standard writing specifications, all indicators in Examples 44-51 meet the standard. Specifically, the suspension rate of the active ingredients after heat storage is higher than 95%, and the heat storage stability and wetting and penetration performance are excellent.

[0096] Comparative Example 1: 13% ivermectin·chlorfenapyr SC (refer to Example 3 of Chinese Patent Application CN200510132849.5), the specific composition is shown in the table:

[0097] Table 9. 13% ivermectin and chlorfenapyr SC and their composition

[0098]

[0099] According to the HG / T2467.5-2003 standard for pesticide suspension concentrates, all indicators in Comparative Example 1 meet the standard. Specifically, the suspension rate of the active ingredient after heat storage is higher than 90%, and the heat storage stability is qualified.

[0100] Test Example 5: Suspension Formulation Test of Ivermectin and Spirotetramethrin

[0101] 1. Experimental Objective

[0102] Based on the different properties and functions of the tested additives, different proportions of active ingredients, different contents of active ingredients, different structural types of additive compositions, and other additives were applied to the formulation to screen and obtain a stable formulation.

[0103] 2. Test methods

[0104] Weigh each component according to the following mass percentages (see Table 10 for specific composition and dosage): pesticide active ingredient 1 (ivermectin), active ingredient 2 (spirotetramat); synergist composition (components A and B); wetting agent; antifreeze (ethylene glycol) total 3%; defoamer (SAG-1522 (Momentive)) total 0.3%; thickener (magnesium aluminum silicate) total 0.5%; the remaining amount is made up with deionized water, with a total weight of 100 g.

[0105] The preparation method of the suspending agent and the method for determining its thermal storage stability are the same as those in Test Example 1.

[0106] 3. Test Results

[0107] Table 10 Composition and dosage of formulation examples

[0108]

[0109] According to the HG / T2467.5-2003 pesticide suspension concentrate product standard writing specifications, all indicators in Examples 52-59 meet the standard. Specifically, the suspension rate of the active ingredients after heat storage is higher than 95%, and the heat storage stability and wetting and penetration performance are excellent.

[0110] Comparative Example 2: 23% ivermectin·spirotetramat SC (refer to Example 13 of Chinese Patent Application CN201910645619.0), the specific composition is shown in the table:

[0111] Table 11 23% Ivermectin and Spirotetramethrin SC and their composition

[0112]

[0113] According to the HG / T2467.5-2003 standard for pesticide suspension concentrates, all indicators in Comparative Example 2 meet the standard. Specifically, the suspension rate of the active ingredient after heat storage is higher than 90%, and the heat storage stability is qualified.

[0114] Test Example 6: Crop Safety Test of Ivermectin-Clostridium Suspension Concentrate

[0115] 1. Experimental Objective

[0116] Based on the performance and characteristics of different adjuvant compositions according to the present invention, crop safety tests were conducted on ivermectin chlorfenapyr suspension to obtain a stable formulation with high safety.

[0117] 2. Experimental subject: Cabbage seedlings.

[0118] 3. Application method and water volume: Apply as a standard foliar spray, using 8 mL of water per plant.

[0119] 4. Plot design: A randomized block arrangement is used, with each plot containing 3 plants, repeated 3 times.

[0120] 5. Experimental investigation and calculation methods: 3 days and 14 days after application, observe all plants in the plot for phytotoxicity, as well as the type and degree of phytotoxicity. 3 plants are investigated in each plot, and 3 leaves are investigated in each plant, for a total of 9 leaves in each plot. The phytotoxicity index is calculated based on this.

[0121] 5.1 The grading standards for pesticide damage are shown in Table 12.

[0122] Table 12 Grading Standards for Drug Damage

[0123]

[0124] 5.2 Formula for calculating phytotoxicity:

[0125]

[0126] 6. Experimental Design and Results

[0127] The standard field application rate was a 2000-fold dilution. Crop safety trials were then conducted at 2 and 4 times this dilution. This experiment was conducted in Taizhou City, Zhejiang Province. No other pesticides were applied in the 20 days prior to and during the experiment.

[0128] Table 13 Crop safety test design and results of formulation examples

[0129]

[0130]

[0131] As shown in Test Example 1 of Table 13, when conventional additives such as sodium dioctyl sulfonate and organosilicon and isomeric alcohol polyoxyethylene ether are used, they have certain advantages over other types of additives in terms of wetting and penetration performance.

[0132] Taking ivermectin and chlorfenapyr suspension concentrates as examples, through the above-mentioned crop safety tests, when conventional adjuvants such as sodium dioctyl sulfosuccinate or organosilicon are used in ivermectin and chlorfenapyr suspension concentrate products (Examples 5 and 6), the risk of phytotoxicity is significantly higher than that in the case of the present invention using isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether as adjuvants (Examples 44 and 45). Specifically, at 4 times the application rate, Examples 5 and 6 showed obvious phytotoxicity, and at 2 times the application rate, there were varying degrees of leaf phytotoxicity; while at 4 times the application rate, Examples 44 and 45 showed partial phytotoxicity, and at 2 times the application rate, there was no obvious phytotoxicity; in comparison, the formulation composition of the present invention significantly improves crop safety.

[0133] Furthermore, in the suspensions of ivermectin and spirotetramat, the risk of phytotoxicity was significantly higher when organosilicon was used as an adjuvant (Example 18) than when isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether were used as adjuvants (Example 52).

[0134] In summary, when preparing suspension products of ivermectin and chlorfenapyr, or ivermectin and spirotetramat, using the specific ratio of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether as adjuvants in this invention can achieve better crop safety.

[0135] Test Example 7: Field efficacy trial of 35% ivermectin·chlorfenapyr SC for controlling citrus pseudomitr mite

[0136] 1. Experimental objective: To test the field control efficacy of different formulation examples against citrus psyllids.

[0137] 2. Target pest: Citrus psoriatic mites (Panonychus citri (McGregor)).

[0138] 3. Application method and water consumption: For standard foliar spraying, the water consumption is 1500 L per hectare (100 L / 667 ㎡).

[0139] 4. Community Design: A randomized block arrangement will be adopted, with the specific arrangement to be determined based on site conditions. The community area is approximately 200 m². 2 Repeat 3 times.

[0140] 5. Experimental survey: Fixed-point survey method, 2 plants were marked in each plot, and 5 leaves of each plant were marked using the "five-point sampling method", and a total of 20 leaves were surveyed in each plot.

[0141] 5.1. Efficacy survey: Investigate the initial insect population before application and conduct surveys 3, 7 and 11 days after application, checking and recording the number of live mites on the leaves.

[0142] 5.2 Crop safety survey: Survey the presence of pesticide damage and its symptoms (e.g., yellowing leaves, wilting or deformity) at 3, 7 and 11 days after application, and record the type and degree of pesticide damage.

[0143] 6. Method for calculating drug efficacy:

[0144]

[0145]

[0146] 7. Experimental Design and Results:

[0147] This experiment was conducted in Linhai City, Zhejiang Province. No other agents were applied 20 days before and during the experiment.

[0148] Table 14 Field efficacy trial design and results of formulation examples

[0149]

[0150] As shown in the table, when the specific ratio of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether of the present invention is used as an adjuvant composition in ivermectin and chlorfenapyr suspension products (Examples 44-47), with the same amount of active ingredient, the control effect on citrus pseudococcus is significantly better than the formulation examples involved in patent CN200510132849.5 (Comparative Example 1), and also better than the formulation examples using fatty amine polyoxyethylene ether alone (Example 2). Specifically, the control efficacy of Example 44 is higher than 95% after 11 days, the control efficacy of Examples 45-47 is higher than 90%, while the control efficacy of Comparative Example 1 is 84.4%, and the control efficacy of Example 2 is 86.0%, indicating a significant improvement in the control efficacy of the suspension of the present invention.

[0151] In contrast, the present invention, using a specific ratio of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether synergist, exhibits a significant synergistic effect in ivermectin and chlorfenapyr suspension products. Furthermore, no phytotoxicity was observed in citrus leaves or fruits during the experiment, indicating that the crop safety is up to standard.

[0152] Test Example 8: Field efficacy trial of 35% ivermectin·chlorfenapyr SC for controlling diamondback moth in rapeseed.

[0153] 1. Experimental objective: To test the field control efficacy of different formulation examples against diamondback moth on rapeseed.

[0154] 2. Target pest: Diamondback moth (Plutella xylostella (Linnaeus)).

[0155] 3. Application method and water consumption: For standard foliar spraying, the water consumption is 675 L per hectare (45 L / 667 ㎡).

[0156] 4. Community Design: A randomized block arrangement will be adopted, with the specific arrangement to be determined based on the site conditions. The community area is approximately 8 square meters. 2 Repeat 3 times.

[0157] 5. Experimental survey: Fixed-point survey method, five plants were marked in each plot using the "five-point sampling method", and two leaves were marked on each plant. A total of 10 leaves were surveyed in each plot.

[0158] 5.1. Pesticide efficacy survey: Survey the initial insect population before application, and conduct surveys 3, 7 and 14 days after application, checking and recording the number of live insects on the leaves.

[0159] 5.2 Crop safety survey: Investigate the presence of pesticide damage and its symptoms (such as yellowing leaves, wilting or deformity) 3, 7 and 14 days after application, and record the type and degree of pesticide damage.

[0160] 6. The method for calculating drug efficacy is the same as in test example 7.

[0161] 7. Experimental Design and Results:

[0162] This experiment was conducted in Taizhou City, Zhejiang Province. No other agents were applied 20 days before and during the experiment.

[0163] Table 15 Field efficacy trial design and results of formulation examples

[0164]

[0165] As shown in the table, when the combination of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether as adjuvants is applied to ivermectin and chlorfenapyr suspension products (Examples 44-47), with the same dosage of active ingredient, the control effect on the diamondback moth of rape is significantly better than that of the formulation examples involved in patent CN200510132849.5 (Comparative Example 1), and also better than the formulation examples using fatty amine polyoxyethylene ether alone (Example 2). Specifically, the control efficacy of Examples 44-46 is higher than 95% 14 days after application, the control efficacy of Example 47 is 94.5%, while the control efficacy of Comparative Example 1 is 72.8% and the control efficacy of Example 2 is 77.1%, indicating that the control efficacy of the suspension of the present invention is significantly improved.

[0166] In contrast, the present invention, with its synergistic adjuvant composition of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether in a specific ratio, showed a significant synergistic effect in ivermectin and chlorfenapyr suspension products. Furthermore, no phytotoxicity was observed in rapeseed leaves or stems during the experiment, indicating that the crop safety was up to standard.

[0167] Test Example 9: Pot efficacy test of 35% ivermectin·spirotetramat SC for controlling cereal aphids

[0168] 1. Experimental objective: To test the control efficacy of different formulation examples against the rice aphid.

[0169] 2. Target pest: Rhopalosiphum padi.

[0170] 3. Application method and water volume: Apply as a standard foliar spray, using 2.5 mL per pot.

[0171] 4. Plot design: 3 pots of wheat per treatment, 10 wheat seedlings per pot, repeated 3 times.

[0172] 5. Experimental survey: Investigate the total number of insects in wheat seedlings within each treatment.

[0173] 5.1. Pesticide efficacy survey: Survey the initial insect population before application, and conduct surveys 3, 7 and 14 days after application, checking and recording the number of live insects on the leaves.

[0174] 5.2 Crop safety survey: Investigate the presence of pesticide damage and its symptoms (such as yellowing leaves, wilting or deformity) 3, 7 and 14 days after application, and record the type and degree of pesticide damage.

[0175] 6. The method for calculating drug efficacy is the same as in test example 7.

[0176] 7. Experimental Design and Results:

[0177] This experiment was conducted in Taizhou City, Zhejiang Province.

[0178] Table 16. Design and Results of Pot Efficacy Tests for Formulation Examples

[0179]

[0180] As shown in the table, when the combination of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether as adjuvants is applied to ivermectin and spirotetramat suspension products (Examples 52-55), with the same dosage of active ingredient, the control effect on *Aphidius oryzae* is significantly better than that of the formulation examples involved in patent CN201910645619.0 (Comparative Example 2), and also better than the formulation examples using fatty amine polyoxyethylene ether alone (Example 16). Specifically, the control efficacy of Examples 52-55 reached its peak 7 days after application, all exceeding 95%, with control efficiencies of 96.8% and 96.6% for Examples 52 and 55, respectively, while the control efficacy of Comparative Example 2 was 90.0% and that of Example 16 was 79.6%. Similarly, the control efficacy of Examples 52-55 exceeded 85% 14 days after application, while the control efficacy of Comparative Example 2 was 80.5% and that of Example 16 was 68.6%, demonstrating a significant improvement in the control efficacy of the suspension formulation of this invention.

[0181] In contrast, the present invention, using a specific ratio of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether synergist, exhibits a significant synergistic effect in ivermectin and spirotetramat suspension products, and no phytotoxicity was observed in wheat leaves during the experiment, indicating that the crop safety is up to standard.

[0182] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Any 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 suspension formulation of ivermectin, characterized in that, The suspending agent comprises, by weight percentage: 1.5% to 40% active ingredient, 2% to 10% synergistic adjuvant composition, 0.1% to 45% other adjuvants, and water to make up to 100%. The active ingredient is ivermectin and component M, where component M is chlorfenapyr or spirotetramat, with a mass ratio of 1:1 to 1:

20. The synergistic adjuvant composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, with a mass ratio of 1:10 to 5:

1.

2. The suspending agent according to claim 1, characterized in that, The suspension comprises, by weight percentage, the following components: 20% to 35% active ingredient, 3% to 6% synergistic adjuvant composition, 0.1% to 20% other adjuvants, and water to make up to 100%. The active ingredient is ivermectin and component M, wherein component M is chlorfenapyr or spirotetramat, and the mass ratio of the two is 1:15 to 1:

20.

3. The suspending agent according to any one of claims 1 or 2, characterized in that, The synergistic additive composition, by weight percentage, is an isomeric alcohol polyoxyethylene ether and a fatty amine polyoxyethylene ether, with a mass ratio of 1:2 to 5:

1.

4. The suspending agent according to claim 1 or 2, characterized in that, The other additives include one or more of wetting agents, thickeners, antifreeze agents, and defoamers.

5. The suspending agent according to claim 3, characterized in that, The molecular formula of the isomeric alcohol polyoxyethylene ether is RO(CH2CH2O). n H, R = C10 or C13, n = 5~12.

6. The suspending agent according to claim 5, characterized in that, The molecular formula of the isomeric alcohol polyoxyethylene ether is RO(CH2CH2O). n H, R=C13, n=5~8.

7. The suspending agent according to claim 3, characterized in that, The structural formula of the fatty amine polyoxyethylene ether is formula (I). , where R = C10, C12 or C18, n+m = 5~15.

8. The suspending agent according to claim 7, characterized in that, The fatty amine polyoxyethylene ether has the structural formula of compound (Ⅰ), where R=C18 and n+m=10~15.

9. The application of the suspension agent according to any one of claims 1 to 8 in the control of agricultural crop pests, wherein the pests include at least one of phytophagous mites, Lepidoptera, Hemiptera, and Thysanoptera.

10. The application according to claim 9, characterized in that, The crops mentioned include food crops, cash crops, fruit trees, vegetables, and medicinal crops.

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