Suspending agent preparation of ivermectin and preparation method thereof

Abstract

The invention relates to an ivermectin suspending agent preparation and a preparation method thereof. The ivermectin suspending agent preparation comprises 1.5%-40% of effective components, 2%-10% of synergistic additive composition, 0.1%-45% of other additives and the balance of water. Wherein the effective components are ivermectin and a component M, the component M is chlorfenapyr or spirotetramat, and the mass ratio of the component M to the chlorfenapyr to the spirotetramat is 1: 1-1: 20; the synergistic additive composition is prepared from isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, and the mass ratio of the isomeric alcohol polyoxyethylene ether to the fatty amine polyoxyethylene ether is (1: 10)-(7.5: 1). Compared with the prior art, the isomeric alcohol polyoxyethylene ether suspending agent can relieve the problem that the heat storage suspension rate is reduced due to the fact that isomeric alcohol polyoxyethylene ether is added into a suspending agent preparation of ivermectin, the control effect on phytophagous mites, lepidoptera pests and the like is improved, and the actual requirements of processing, storage, safety, field application and the like are met.

Description

Technical Field

[0001] The invention relates to the technical field of pesticide preparations, and in particular to an ivermectin suspension preparation and a preparation method thereof. Background Art

[0002] Ivermectin is a semi-synthetic macrocyclic lactone biological pesticide, which is made from the metabolites of Streptomyces avermitilis through hydrogenation reduction. It has high killing activity against agricultural pests such as mites and lepidopteran pests, and has the characteristics of high efficiency, low toxicity, environmental protection, good rapidity and short duration. At the same time, chlorfenapyr, as a pyrrole chemical pesticide, has a good control effect on agricultural pests such as mites, nematodes and lepidopteran pests, and shows a long duration in field applications; spirotetramat, as a tetronic acid compound, has unique bidirectional systemic conduction properties, which is manifested as a long onset time and field duration.

[0003] Chinese patent application CN200510132849.5 discloses a pesticide composition of ivermectin and cypermethrin and its field use for killing insects and 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 formulate the compound composition of the active ingredients of pesticides, and none of the formulation examples mentioned have been developed for synergistic effects such as control effects. In practical applications, the stability, spreadability, permeability and control effects of ivermectin and cypermethrin or spirotetramat suspension products need to be further improved. It is urgent to develop more stable and efficient suspension preparations to meet the actual needs of processing, storage, safety and field application. Summary of the invention

[0004] In view of the shortcomings of the prior art, the present invention aims to provide a suspension preparation of ivermectin and a preparation method thereof. The present invention obtains a suspension system with stable performance through a specific synergistic adjuvant composition. The preparation product has good heat storage stability and can improve the control effect of the active ingredients on mites and lepidopteran pests, etc., meeting the actual needs of processing, storage, safety and field application.

[0005] To achieve this object, the present invention adopts the following technical solutions:

[0006] A suspension preparation of ivermectin, the suspension preparation comprises the following components by weight percentage: 1.5% to 35% of active ingredient, 2% to 10% of synergistic auxiliary composition, 0.1% to 45% of other auxiliary agents, and water is used to make up to 100%. The active ingredient is ivermectin and component M, component M is chlorfenapyr or spirotetramat, and the mass ratio of the two is 1:1 to 1:20; the synergistic auxiliary composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, and the mass ratio of the two is 1:10 to 7.5:1.

[0007] Preferably, the suspension comprises the following ingredients: 20% to 35% of active ingredient, 3% to 6% of synergistic adjuvant composition, 0.1% to 20% of other adjuvants, and water is added to 100%. The active ingredient is ivermectin and ingredient M, and ingredient M is chlorfenapyr or spirotetramat, and the mass ratio of the two is 1:15 to 1:20.

[0008] Furthermore, the synergistic adjuvant composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, and the mass ratio of the two is 1:2 to 5:1. In the suspension concentrate of the present invention, the adjuvant used is the conventional adjuvant and formulation auxiliary component required for the preparation of pesticide formulations, including one or more of wetting agents, thickeners, antifreeze agents and defoaming agents.

[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, polyvinyl pyrrolidone, carboxyethyl cellulose, methyl cellulose, magnesium aluminum silicate and polyvinyl alcohol;

[0011] Specifically, the defoaming agent is selected from one or more of sucrose fatty acid esters, silicones, fatty acids, mineral oils, and alcohols;

[0012] Specifically, the antifreeze agent 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 dosage form and achieve the field application effect. The types, functions, and application techniques of the auxiliary materials are referred to Zhang Xiaojun, Liu Guangwen, et al. [Pesticide Adjuvants, (2018, Chemical Industry Press)].

[0014] In the synergistic aid composition of the suspension agent of the present invention, the molecular formula of the isomeric alcohol polyoxyethylene ether is RO(CH2CH2O) n H, wherein R=C10 or C13, and n=5-12.

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

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

[0017]

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

[0019] The suspension preparation of the present invention can be used for preventing and controlling phytophagous mites, lepidopteran pests, hemipteran pests and thysanoptera pests on agricultural crops. The phytophagous mites include Panonychus mites, cotton spider mites, cinnabarinus spider mites, two-spotted spider mites, hawthorn spider mites, etc. The lepidopteran pests include Plutella xylostella, Spodoptera exigua, Spodoptera litura, Fall Armyworm, Spodoptera two-spotted, etc. The hemipteran pests include Aphid avenae, Macrosipter avenae, Schizaphis graminis, Laodelphax striatellus, Whiteback Planthopper, Bemisia tabaci, scale insects, etc. The thysanoptera pests include Melon thrips, Onion thrips, Rice thrips, Western flower thrips, etc.

[0020] The crops 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, kiwis, hawthorns, etc. Vegetables include eggplant, tomato and other Solanaceae crops, cucumber, early melon, zucchini and other Cucurbitaceae crops, cabbage, Chinese cabbage and other Cruciferae crops; Medicinal crops include ginseng, wolfberry, astragalus, etc.

[0021] Pesticide suspension concentrates process water-insoluble solid active ingredients of pesticides into fine particles (generally with an average particle size of less than 5 μm), which are suspended in water under the steric hindrance effect of surfactants or the action of charges to form a relatively stable suspension system. Specifically, since pesticide suspension concentrates are a highly dispersed multiphase complex system, their stability is related to many factors. In addition to the physical and chemical properties of the active ingredients of the pesticides themselves (such as morphology, melting point, solubility, chemical stability, light stability and thermal stability, etc.), the compatibility of adjuvants (such as wetting agents, dispersants, antifreeze agents, thickeners, preservatives, defoaming agents and other adjuvants, etc.) also needs to be considered. The interaction between them will affect the stability of the suspension concentrate.

[0022] With the increasing problem of resistance accumulation of pesticide active ingredients and the diversification and complexity of field pests and diseases, the demand for the prevention effect of pesticide products has gradually increased accordingly. Pesticide synergistic adjuvants can improve the wettability, spreadability, permeability and adhesion of pesticide formulations on plant surfaces to a certain extent, increase the contact area between pesticides and target organisms or crops, reduce the escape rate of target organisms, and expand the protection range of crops, thereby improving the utilization rate of pesticide active ingredients and enhancing crop prevention and control effects.

[0023] Additives such as isomeric alcohol polyoxyethylene ethers have synergistic functions in some suspension systems, which help to enhance the spreading, wetting or penetration properties of active ingredients and improve the efficacy of pesticide products. However, in practical applications, when a single adjuvant such as isomeric alcohol polyoxyethylene ether is introduced into the compound suspension products of ivermectin and chlorfenapyr, or ivermectin and spirotetramat, the original adjuvant dispersion system is affected and the stability is significantly reduced. Specifically, the suspension rate of ivermectin drops significantly after hot storage, and it is prone to problems such as water precipitation during hot storage, paste formation or decreased dilution stability, which reduces the commerciality of the formulation product or shortens the shelf life. Therefore, the addition of synergistic adjuvants often places higher requirements on the adjuvant dispersion system of suspension products. In summary, the permeability, stability and prevention effect of ivermectin suspension products need to be further improved.

[0024] The inventors of the present application have discovered that the above-mentioned problems can be better solved by simultaneously introducing fatty alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers as auxiliary agents as an auxiliary agent composition, thereby obtaining a suspension formulation with good stability, dispersion and suspension properties and permeability properties. In particular, when an octadecylamine polyoxyethylene ether auxiliary agent with a higher degree of polymerization is used, the comprehensive performance of the formulation is better.

[0025] Compared with the ivermectin suspension preparation of the prior art, the advantages of the present invention are:

[0026] 1) Enhanced stability: The auxiliary agent composition improves the dispersion stability, heat storage stability and long-term stability of the ivermectin suspension product while improving the permeability of the preparation.

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

[0028] 3) Crop safety: The adjuvant composition effectively reduces the risk of phytotoxicity caused by synergistic adjuvants, while improving the control effect and ensuring the safety of crop leaves, stems and fruits. DETAILED DESCRIPTION

[0029] In order to better understand the essence of the present invention, the following embodiments are used to further illustrate the content of the present invention, but they cannot be regarded as limiting the present invention. The content mentioned in the embodiments is not limiting the present invention. The material formula selection can be adapted to local conditions and has no substantial effect on the results. Unless otherwise specified, the following percentages are weight percentages.

[0030] Test Example 1: Test on the type of additives for suspension concentrates

[0031] 1. Purpose of the test

[0032] According to the different properties and functions of the tested additives, conformity selection was carried out for different categories of additives such as isomeric alcohol polyoxyethylene ethers, fatty amine polyoxyethylene ethers, phosphate esters, sulfate esters, sulfonates, naphthalene sulfonates, and polycarboxylates. Appropriate additives were combined into 10 compound formulas and 4 single-use formulas, and the test was carried out according to the repeated test method.

[0033] 2. Test methods

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

[0035] Thermal storage stability test: Referring to GB / T 19136-2021, the samples were placed at 54±2℃ for 14 days to test indicators such as the appearance of the preparation, the mass fraction of the active ingredient and the suspension rate.

[0036] Penetration wettability test: Referring to GB / T 11983-2008, take the auxiliary composition (components A and B, see Table 3 for specific composition and content) and prepare the dilution solution with the same dilution multiple, and adjust the volume to 1000mL. Assemble and adjust the position of the plane trident sliding bracket on the immersion clamp handle so that the raw cotton cloth disc clamped by it is about 40mm below the liquid surface. Pour the solution to be tested into the measuring beaker, remove the foam on the liquid surface, clamp the raw cotton cloth disc with the immersion clamp, and immerse it in the solution. When the lower end of the cloth piece contacts the solution, start timing, and when the cloth piece starts to sink automatically, stop timing, and the time interval between the two is counted as the wetting time.

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

[0038] Table 1 Hot storage stability classification standard (54℃14 days)

[0039] series Grading Standards + Ivermectin suspension rate / %: <60 ++ Ivermectin suspension rate / %: 60~80 +++ Ivermectin suspension rate / %: 80~90 ++++ Ivermectin suspension rate / %: 90~95 +++++ Ivermectin suspension rate / %:>95

[0040] Table 2 Wetting and permeability classification standards

[0041] series Grading Standards + Wetting time / s:>140 ++ Wetting time / s: 70~140 +++ Wetting time / s: 60~70 ++++ Wetting time / s: 50~60 +++++ Wetting time / s: 40~50 ++++++ Wetting time / s: <40

[0042] The above test was repeated, wherein the content of the pesticide active ingredient 1 (ivermectin) was 2%, the content of the active ingredient 2 (spirotetramat) was 30%, and the rest was similar.

[0043] 3. Experimental design and results

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

[0045] Table 3 Formulation Examples Auxiliary Components and Dosages The compatibility of different types of auxiliary compositions with the suspension concentrate is obtained based on Table 3, as shown in Table 4.

[0046]

[0047] Table 4 Formula compatibility of different types of auxiliary compositions

[0048]

[0049]

[0050] As can be seen from the table, different types of single auxiliary agents are used in Examples 1 to 6. When a single auxiliary agent such as sodium salt of dioctyl sulfonated succinate, silicone or isomeric alcohol polyoxyethylene ether is used, the permeability of the suspension is better, but there is a problem of poor heat storage stability. On this basis, when Examples 7 to 12 use a combination of isomeric alcohol polyoxyethylene ether or fatty amine polyoxyethylene ether as an auxiliary agent, the addition of a combination of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether as an auxiliary agent in Example 9 can greatly improve the heat storage stability and permeability of the preparation, which is specifically manifested in that the suspension rate of the active ingredient in the heat storage stability is 90 to 95%, and the wetting time in the permeability is 50 to 60 seconds. In addition, similar tests of several other auxiliary agents or combined auxiliary agents were conducted, and only Examples 13 to 14 are listed in the table, and no better combination has been obtained yet.

[0051] Among the suspension preparations of ivermectin and spirotetramat, some results were selected as follows:

[0052] Table 5: Formula compatibility of different types of auxiliary compositions

[0053]

[0054] Similarly, in the suspensions of ivermectin and spirotetramat, single adjuvants such as sodium dioctyl sulfonated succinate, silicone or isomeric alcohol polyoxyethylene ether are used in Examples 15, 17 and 18, and the permeability of the suspensions is better, but the heat storage stability is poor; in Example 19, a combination of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether is added. Compared with the other adjuvant compositions in Examples 20 to 21, the heat storage stability and permeability of the preparation can be greatly improved, which is specifically manifested in that the suspension rate of the active ingredient in the heat storage stability is 90 to 95%, and the wetting time in the permeability is 50 to 60 seconds.

[0055] Comprehensive comparison shows that 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 has better formula adaptability, which is specifically manifested in good heat storage stability and better permeability. That is, the active ingredients in the preparation can be stably suspended in the diluted solution, with good dispersion and suspension properties, which helps its diffusion and penetration on the plant surface, thereby improving the prevention effect of the preparation, and can be further screened as a synergistic adjuvant composition.

[0056] Test Example 2: Proportion test of auxiliary agent composition

[0057] 1. Purpose of the test

[0058] According to the different properties and functions of the additives, isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers are used as components A and B of the additive composition, combined in different proportions and applied in the formula to screen the appropriate proportion of the synergistic additive composition.

[0059] 2. Test methods

[0060] Weigh each component according to the following mass percentage: the content of pesticide active ingredient 1 (ivermectin) is 1.7%, the content of active ingredient 2 (chlorfenapyr) is 33.3%; the total amount of the synergistic adjuvant composition (component A is isomeric alcohol polyoxyethylene ether, component B is fatty amine polyoxyethylene ether, and the specific proportions are shown in Table 6) is 3%; the total amount of wetting agent (naphthalenesulfonate condensate) is 1%; the total amount of antifreeze (ethylene glycol) is 3%; the total amount of defoaming agent (SAG-1522 (Maitu)) is 0.3%; the total amount of thickener (magnesium aluminum silicate) is 0.5%; the remaining amount is supplemented with deionized water, and the total weight is 100g.

[0061] The preparation method of the suspension, the heat storage stability determination and the wetting permeability test method are the same as those in Test Example 1.

[0062] The above test was repeated, wherein the content of the pesticide active ingredient 1 (ivermectin) was 2%, the content of the active ingredient 2 (spirotetramat) was 30%, and the rest was similar.

[0063] 3. Experimental design and results

[0064] Table 6 Formula matching of different proportions of auxiliary compositions

[0065]

[0066] It can be seen from the table that, taking the suspension of ivermectin and chlorfenapyr as an example, when the auxiliary composition of isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ethers is applied to the suspension product of ivermectin in Examples 9 and Examples 22 to 29, when the ratio of component A:B is 1:10 to 5:1, the heat storage stability is significantly better than other ratios; when the ratio of component A:B is 1:2 to 5:1, the permeability is significantly better than other ratios, and the wetting time is less than 60 seconds.

[0067] Similar results were obtained by applying the above ratio to the suspension of ivermectin and spirotetramat. When the ratio of auxiliary component A:B was 1:10 to 5:1, the permeability was also excellent. Preferably, A:B = 1:2 to 5:1.

[0068] Comprehensive comparison shows that when preparing the suspension of ivermectin and chlorfenapyr suspension, or the suspension of ivermectin and spirotetramat, when the isomeric alcohol polyoxyethylene ether and the fatty amine polyoxyethylene ether are used as the synergistic auxiliary composition and the mass ratio of them is 1:10-5:1, the heat storage stability and permeability of the product are better; further, when the mass ratio is 1:2-5:1, the heat storage stability and permeability of the product are better than other ratios, and there is a significant performance improvement.

[0069] Test Example 3: Test on the type of auxiliary agent composition

[0070] 1. Purpose of the test

[0071] According to the different properties and functions of the tested auxiliary agents, different structural types of isomeric alcohol polyoxyethylene ethers and fatty amine polyoxyethylene ether auxiliary agents are used as components A and B of the auxiliary agent composition to screen the appropriate type of synergistic auxiliary agent composition.

[0072] 2. Test methods

[0073] Weigh each component according to the following mass percentage: the content of pesticide active ingredient 1 (ivermectin) is 1.7%, the content of active ingredient 2 (chlorfenapyr) is 33.3%; the synergistic adjuvant composition (component A is 1%, component B is 2%, and the specific structural composition is shown in Table 7); the total amount of wetting agent (naphthalenesulfonate condensate) is 1%; the total amount of antifreeze (ethylene glycol) is 3%; the total amount of defoaming agent (SAG-1522 (Maitu)) is 0.3%; the total amount of thickener (magnesium aluminum silicate) is 0.5%; the remaining amount is supplemented with deionized water, and the total weight is 100g.

[0074] The preparation method of the suspension, the heat storage stability determination and the wetting permeability test method are the same as those in Test Example 1.

[0075] The above test was repeated, wherein the content of the pesticide active ingredient 1 (ivermectin) was 2%, the content of the active ingredient 2 (spirotetramat) was 30%, and the rest was similar.

[0076] 3. Experimental design and results

[0077] Isomeric alcohol polyoxyethylene ether is used as component A, and its chemical formula is RO(CH2CH2O)nH; fatty amine polyoxyethylene ether is used as component B, and its chemical structure is shown in the figure. Auxiliary components with different chemical structures are selected and applied to the formula, as shown in Table 6.

[0078]

[0079] Table 7 Formula matching of different chemical structure additive compositions

[0080]

[0081]

[0082] As can be seen from the table, taking the suspension of ivermectin and chlorfenapyr as an example, the heat storage stability and permeability of Examples 30 to 43 are better than those of other types of adjuvant combinations, which proves that when the isomeric alcohol polyoxyethylene ether and the fatty amine polyoxyethylene ether are a synergistic adjuvant composition, they are well adapted to the suspension product of ivermectin. Among them, 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 formula adaptability is better.

[0083] Further, the formula adaptability of some combinations is better than that of the synergistic auxiliary agent composition of other structural compositions. In Examples 30 to 35, when R of component A = C13 and R of component B = C18, its heat storage stability is better (Example 35); wherein, in Examples 35 to 43, when n of component A = 5, 6 or 8, and n+m of component B = 10 or 15 (specifically Examples 35 to 36, Examples 38 to 39 and Examples 42 to 43), its heat storage stability and permeability are better. Specifically, in the present 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 dispersion suspension, heat storage stability and permeability of the suspending agent are excellent.

[0084] Furthermore, the preferred adjuvant formula is applied to the suspension of ivermectin and spirotetramat, and the suspension has excellent dispersion and suspension properties, heat storage stability and permeability.

[0085] Test Example 4: Test on the suspension formulation of ivermectin and chlorfenapyr

[0086] 1. Purpose of the test

[0087] According to the different properties and functions of the tested auxiliary agents, different proportions of active ingredients, different contents of active ingredients, auxiliary agent combinations of different structural types and other auxiliary agents are applied to the formula to screen and obtain a stable formula.

[0088] 2. Test methods

[0089] Weigh each component according to the following mass percentage (see Table 8 for specific composition and amount): pesticide active ingredient 1 (ivermectin), active ingredient 2 (chlorfenapyr); synergistic adjuvant composition (components A and B); wetting agent; antifreeze (ethylene glycol) total amount is 3%; defoamer (SAG-1522 (Maitu)) total amount is 0.3%; thickener (magnesium aluminum silicate) total amount is 0.5%; the remaining amount is supplemented with deionized water, and the total weight is 100 g.

[0090] The preparation method of the suspension concentrate and the heat storage stability determination method are the same as those in Test Example 1.

[0091] 3. Test results

[0092] Table 8 Composition and dosage of the preparation examples

[0093]

[0094]

[0095] According to the HG / T2467.5-2003 pesticide suspension product standard, all indicators of Examples 44 to 51 meet the standards. Specifically, the suspension rate of the active ingredient after hot storage is higher than 95%, and the hot storage stability and wetting permeability 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 its composition

[0098] composition Percentage effect 90% Ivermectin original drug 1％ Active ingredient 1 98% Chlorfenapyr TC 12％ Active ingredient 2 Sodium butylnaphthalenesulfonate pull-off powder BX (Shanghai Hongxin) 0.6％ Wetting Agents Sodium Methylene Bisnaphthalene Sulfonate NNO (Pan Asia) 2.5％ Dispersants Xanthan gum 0.2％ Thickener Ethylene glycol 6％ antifreeze Deionized water Top up 100% Aqueous medium

[0099] According to the HG / T2467.5-2003 pesticide suspension product standard, all indicators of comparative example 1 meet the standards. Specifically, the suspension rate of the active ingredient after hot storage is higher than 90%, and the hot storage stability is qualified.

[0100] Test Example 5: Suspension formulation test of ivermectin and spirotetramat

[0101] 1. Purpose of the test

[0102] According to the different properties and functions of the tested auxiliary agents, different proportions of active ingredients, different contents of active ingredients, auxiliary agent combinations of different structural types and other auxiliary agents are applied to the formula to screen and obtain a stable formula.

[0103] 2. Test methods

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

[0105] The preparation method of the suspension concentrate and the heat storage stability determination method 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 product standard, all indicators of Examples 52 to 59 meet the standards. Specifically, the suspension rate of the active ingredient after hot storage is higher than 95%, and the hot storage stability and wetting permeability 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 Spirotetramat SC and its composition

[0112]

[0113]

[0114] According to the HG / T2467.5-2003 pesticide suspension product standard, all indicators of Comparative Example 2 meet the standards. Specifically, the suspension rate of the active ingredient after hot storage is higher than 90%, and the hot storage stability is qualified.

[0115] Test Example 6: Crop Safety Test of Ivermectin-Chlorfenapyr Suspension Concentrate

[0116] 1. Purpose of the test

[0117] According to the performance and characteristics of different adjuvant compositions of the present invention, crop safety tests were conducted on the ivermectin chlorfenapyr suspension concentrate to obtain a stable formula with higher safety.

[0118] 2. Experimental subjects: Cabbage seedlings.

[0119] 3. Application method and water dosage: Normal foliar spray, 8 mL of water per plant.

[0120] 4. Plot design: A random block arrangement was used, with 3 strains in each plot, repeated 3 times.

[0121] 5. Test investigation and calculation method: 3d and 14d after application of pesticides, observe all plants in the plot for pesticide damage and the type and degree of pesticide damage. In each plot, investigate 3 plants, 3 leaves for each plant, and a total of 9 leaves in each plot, and calculate the pesticide damage index based on this.

[0122] 5.1. See Table 12 for the classification standards of pesticide damage.

[0123] Table 12 Classification standards for pesticide damage

[0124] Grading Standards series No drug damage 0 Drug spot area ratio / %: <25 1 Drug spot area ratio / %: 25-50 2 Drug spot area ratio / %: 51-75 3 Drug spot area ratio / %: 75-100 4

[0125] 5.2. Calculation formula for pesticide damage:

[0126]

[0127] 6. Experimental Design and Results

[0128] The conventional field application rate was 2000 times diluted, and on this basis, the application rate was increased to 2 and 4 times for crop safety tests. This experiment was conducted in Taizhou City, Zhejiang Province, and no other pesticides were applied 20 days before and during the test.

[0129] Table 13 Crop safety test design and results of formulation examples

[0130]

[0131]

[0132] It can be seen from Test Example 1 in Table 13 that when conventional additives such as sodium salt of dioctyl sulfonate succinate and silicone and isomeric alcohol polyoxyethylene ether are used, they have certain advantages over other types of additives in terms of wetting and penetration properties.

[0133] Taking ivermectin and chlorfenapyr suspension as examples, through the above-mentioned crop safety test, when conventional adjuvants such as sodium salt of dioctyl sulfonated succinate or silicone are used in ivermectin and chlorfenapyr suspension products (Examples 5 and 6), the risk of phytotoxicity is significantly higher than the case where isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether are used as adjuvant compositions in the present invention (Examples 44 and 45). Specifically, at 4 times the application rate, Examples 5 and 6 have obvious phytotoxicity, and at 2 times the application rate, there are different degrees of leaf phytotoxicity; while at 4 times the application rate, Examples 44 and 45 have partial phytotoxicity, and at 2 times the application rate, there is no obvious phytotoxicity; in contrast, the formulation composition of the present invention significantly improves crop safety.

[0134] In addition, in the suspension of ivermectin and spirotetramat, when silicone is used as a synergistic adjuvant (Example 18), the risk of phytotoxicity is significantly higher than when isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether are used as an adjuvant composition (Example 52).

[0135] Comprehensive comparison shows that 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 of the present invention as the adjuvant composition can obtain better crop safety.

[0136] Test Example 7: Field efficacy test of 35% ivermectin·chlorfenapyr SC for controlling citrus mites

[0137] 1. Experimental purpose: To test the field control effects of different formulation examples on Panonychus citri.

[0138] 2. Target of prevention and control: Panonychus citri (McGregor).

[0139] 3. Application method and water consumption: Normal foliar spray, water consumption per hectare is 1500L (100L / 667㎡).

[0140] 4. Plot design: Random block arrangement is adopted, which is determined on site. The plot area is about 200m 2 , repeat 3 times.

[0141] 5. Experimental investigation: Fixed-point investigation method, mark 2 plants in each plot, mark 5 leaves of each plant with the "five-point sampling method", and investigate a total of 20 leaves in each plot.

[0142] 5.1. Efficacy investigation: Investigate the insect population base before applying the pesticide, and investigate once each at 3, 7, and 11 days after applying the pesticide, and check and record the number of live mites on the leaves.

[0143] 5.2. Crop safety survey: Investigate whether there is any pesticide damage and its symptoms (such as yellow leaves, dryness or deformity) 3, 7 and 11 days after application, and record the type and extent of the pesticide damage.

[0144] 6. Calculation method of drug efficacy:

[0145]

[0146] 7. Experimental design and results:

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

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

[0149]

[0150] As can be seen from 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 for ivermectin and chlorfenapyr suspension products (Examples 44-47), under the same dosage of active ingredients, with citrus mites as the control target, its control effect is significantly better than the formulation example involved in patent CN200510132849.5 (Comparative Example 1), and is also better than the formulation example using fatty amine polyoxyethylene ether alone (Example 2). Specifically, the control effect of Example 44 is higher than 95% 11 days after the drug, and the control effect of Examples 45-47 is higher than 90%, while the control effect of Comparative Example 1 is 84.4%, and the control effect of Example 2 is 86.0%, and the control effect of the suspension of the present invention is significantly improved.

[0151] In contrast, the synergistic adjuvant composition of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether in a specific ratio in the present invention showed obvious synergistic effect in the suspension products of ivermectin and chlorfenapyr, and no phytotoxicity was observed on citrus leaves or fruits during the test, and the crop safety was qualified.

[0152] Test Example 8: Field efficacy test of 35% ivermectin·chlorfenapyr SC against Plutella xylostella

[0153] 1. Experimental purpose: To test the field control effects of different formulation examples on Plutella xylostella.

[0154] 2. Target of prevention and control: Diamondback moth (Plutella xylostella (Linnaeus)).

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

[0156] 4. Plot design: Random block arrangement is adopted, which is determined on site. The plot area is about 8m 2 , repeat 3 times.

[0157] 5. Experimental investigation: Fixed-point investigation method, 5 plants were marked in each plot using the "five-point sampling method", 2 leaves were marked for each plant, and a total of 10 leaves were investigated in each plot.

[0158] 5.1. Efficacy investigation: Investigate the insect population base before applying the pesticide, and investigate once each 3, 7, and 14 days after applying the pesticide, and check and record the number of live insects on the leaves.

[0159] 5.2. Crop safety investigation: Investigate whether there is any pesticide damage and its symptoms (such as yellow leaves, dryness or deformity) 3, 7 and 14 days after application, and record the type and extent of the pesticide damage.

[0160] 6. The calculation method of drug efficacy is the same as that of Test Example 7.

[0161] 7. Experimental design and results:

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

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

[0164]

[0165] As can be seen from the table, when the isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether are used as adjuvant compositions in ivermectin and chlorfenapyr suspension products (Examples 44-47), with the same dosage of active ingredients, the control effect of Plutella xylostella is significantly better than the formulation example involved in patent CN200510132849.5 (Comparative Example 1), and is also better than the formulation example using fatty amine polyoxyethylene ether alone (Example 2). Specifically, the control effect of Examples 44-46 14 days after the drug is higher than 95%, the control effect of Example 47 is 94.5%, while the control effect of Comparative Example 1 is 72.8%, and the control effect of Example 2 is 77.1%. The control effect of the suspension of the present invention is significantly improved.

[0166] In contrast, the synergistic adjuvant composition of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether in a specific ratio in the present invention showed obvious synergistic effect in the suspension product of ivermectin and chlorfenapyr, and no phytotoxicity was observed on rapeseed leaves or stems during the test, and the crop safety was qualified.

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

[0168] 1. Experimental purpose: To test the control effect of different formulation examples on the aphid.

[0169] 2. Target of prevention and control: Grain aphid (Rhopalosiphum padi).

[0170] 3. Application method and water dosage: normal foliar spray, 2.5 mL per pot.

[0171] 4. Plot design: Each treatment had 3 pots of wheat, 10 wheat seedlings in each pot, and repeated 3 times.

[0172] 5. Experimental investigation: Investigate the total insect population of wheat seedlings in each treatment.

[0173] 5.1. Efficacy investigation: Investigate the insect population base before applying the pesticide, and investigate once each 3, 7, and 14 days after applying the pesticide, and check and record the number of live insects on the leaves.

[0174] 5.2. Crop safety investigation: Investigate whether there is any pesticide damage and its symptoms (such as yellow leaves, dryness or deformity) 3, 7 and 14 days after application, and record the type and extent of the pesticide damage.

[0175] 6. The calculation method of drug efficacy is the same as that of Test Example 7.

[0176] 7. Experimental design and results:

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

[0178] Table 16 Potted plant efficacy test design and results of formulation examples

[0179]

[0180] As can be seen from the table, when isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether are used as adjuvant compositions for ivermectin and spirotetramat suspension products (Examples 52-55), under the same dosage of active ingredients, with rapeseed moth as the control target, its control effect is significantly better than the formulation example involved in patent CN201910645619.0 (Comparative Example 2), and is also better than the formulation example using fatty amine polyoxyethylene ether alone (Example 16). Specifically, the control effect of Examples 52-55 reaches a peak 7d after medication, both higher than 95%, and the control effects of Examples 52 and 55 are 96.8% and 96.6% respectively, while the control effect of Comparative Example 2 is 90.0%, and the control effect of Example 16 is 79.6%; similarly, the control effect of Examples 52-55 14d after medication is higher than 85%, while the control effect of Comparative Example 2 is 80.5%, and the control effect of Example 16 is 68.6%, and the control effect of the suspension of the present invention is significantly improved.

[0181] In contrast, the synergistic adjuvant composition of isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether in a specific ratio in the present invention showed obvious synergistic effect in the suspension product of ivermectin and spirotetramat, and no phytotoxicity to wheat leaves was observed during the test, and the crop safety was qualified.

[0182] The above description is only a preferred embodiment of the present invention and does not limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A suspension preparation of ivermectin, characterized in that: The suspension comprises the following components by weight: 1.5% to 40% of active ingredient, 2% to 10% of synergistic auxiliary composition, and 0.1% to 45% of other auxiliary agents, which are supplemented to 100% with water, wherein the active ingredient is ivermectin and component M, component M is cypermethrin or spirotetramat, and the mass ratio of the two is 1:1 to 1:20; the synergistic auxiliary composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, and the mass ratio of the two is 1:10 to 7.5:

1.

2. The suspending agent according to claim 1, characterized in that The suspension comprises the following ingredients by weight: 20% to 35% of active ingredient, 3% to 6% of synergistic auxiliary composition, 0.1% to 20% of other auxiliary agents, and water is used to make up to 100%, wherein the active ingredient is ivermectin and ingredient M, ingredient 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 In terms of weight percentage, the synergistic auxiliary agent composition is isomeric alcohol polyoxyethylene ether and fatty amine polyoxyethylene ether, and the mass ratio of the two is 1:2 to 5:

1.

4. The suspending agent according to any one of claims 1 or 2, characterized in that The other auxiliary agents include one or more of a wetting agent, a thickening agent, an antifreeze agent and a defoaming agent.

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 suspension 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 suspension according to claim 3, characterized in that The structural formula of the fatty amine polyoxyethylene ether is a compound of formula (I), wherein R=C10, C12 or C18, and n+m=5-15.

8. The suspension concentrate according to claim 7, characterized in that The structural formula of the fatty amine polyoxyethylene ether is the compound of formula (I), wherein R=C18, n+m=10-15.

9. Use of the suspension concentrate according to any one of claims 1 to 8 in controlling insect pests of agricultural crops, wherein the insect pests include at least one of herbivorous mites, Lepidoptera, Hemiptera and Thysanoptera.

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

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