WO2020042730A1 - 一种含联苯类化合物的液体制剂及其应用 - Google Patents

一种含联苯类化合物的液体制剂及其应用 Download PDF

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Publication number
WO2020042730A1
WO2020042730A1 PCT/CN2019/092162 CN2019092162W WO2020042730A1 WO 2020042730 A1 WO2020042730 A1 WO 2020042730A1 CN 2019092162 W CN2019092162 W CN 2019092162W WO 2020042730 A1 WO2020042730 A1 WO 2020042730A1
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Prior art keywords
compound
wetting
liquid preparation
stabilizer
balance
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PCT/CN2019/092162
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English (en)
French (fr)
Inventor
丑靖宇
遇璐
宋玉泉
吴鸿飞
于海波
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沈阳中化农药化工研发有限公司
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Application filed by 沈阳中化农药化工研发有限公司 filed Critical 沈阳中化农药化工研发有限公司
Priority to JP2021510308A priority Critical patent/JP7253040B2/ja
Priority to CN201980055813.1A priority patent/CN112930115B/zh
Priority to EP19853373.9A priority patent/EP3845065A4/en
Publication of WO2020042730A1 publication Critical patent/WO2020042730A1/zh
Priority to US17/187,877 priority patent/US20210176988A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/02—Acaricides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/22—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing ingredients stabilising the active ingredients
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/16—Oxygen or sulfur directly attached to an aromatic ring system with two or more oxygen or sulfur atoms directly attached to the same aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • A01N41/10—Sulfones; Sulfoxides

Definitions

  • the invention belongs to the field of acaricides, and relates to a liquid preparation containing a biphenyl compound and an application thereof.
  • Compound A The biphenyl compounds (hereinafter referred to as Compound A) disclosed in the Chinese invention patent CN 105541682 A have excellent acaricidal control effects and have broad market application prospects.
  • the structure of compound A is as follows:
  • the use form of the compound can be dry powder, wettable powder, emulsifiable concentrate, microemulsion, paste, granule, solution, suspension, etc., but the use form of the compound described in the patent is They are prepared in a known manner, for example, optionally in the presence of a surfactant, by diluting or dissolving the active substance with a solvent medium and / or a solid diluent, but the choice of the type of compound known in the art depends on the particular application.
  • the melting point is greater than 60 ° C
  • the solubility in water is less than 200 mg / L
  • the melting points of some compounds are around 60 ° C.
  • the melting point of pendimethalin is 54 ° C to 58 ° C
  • the melting point of nitriconazole is 63-68 ° C.
  • pesticide liquid preparation products including but not limited to suspending agents, water emulsions, microemulsions, and solubilizing agents, will all fail.
  • the effect of the medicine is significantly affected, and even it becomes unusable. Therefore, it is of great significance to develop pesticide liquid formulations that are suitable for the active ingredient, have acceptable properties, and do not increase significantly in particle size.
  • the object of the present invention is to provide a liquid preparation containing a biphenyl compound and its application.
  • the structural formula of compound A is as follows,
  • R 1 and R 2 are each independently selected from hydrogen, C 1 -C 8 alkyl, halo C 1 -C 8 alkyl, C 2 -C 8 alkenyl, halo C 2 -C 8 alkenyl , C 2 -C 8 alkynyl, halo C 2 -C 8 alkynyl, cyano C 1 -C 8 alkyl or cyano halo C 1 -C 8 alkyl; m, n are each independently selected from 0 , 1 or 2.
  • the acaricide liquid formulation is a solution, an oil, a film spreading oil, a dispersible liquid, an aqueous emulsion, an oil emulsion, an emulsifiable concentrate, a microemulsion, a suspension, a microcapsule suspension, an oil suspension, and a dispersible Oil suspension or ultra-low solubility liquid.
  • the acaricide formulation is an aqueous emulsion, suspension, dispersible oil suspension, emulsifiable concentrate or microemulsion.
  • the auxiliary agent in the liquid preparation further includes a stabilizer; wherein the stabilizer is glycyrrhizin.
  • the water emulsion is, based on the mass percentage content, Compound A 2% -60%, solvent 2-20%, wetting and dispersing agent 1% -30%, stabilizer 0% -3%, and the balance is deionized water;
  • the suspending agent based on the mass percentage content, is 2% -60% of compound A, 5% -30% of wetting and dispersing agent, 0% -3% of stabilizer, and the balance is deionized water;
  • the dispersible oil suspension agent based on the mass percentage content, is 2% -60% of Compound A, 5% -30% of wetting and dispersing agent, 0% -3% of stabilizer, and the balance is the oil of the dispersion medium;
  • the emulsifiable concentrate based on the mass percentage content, is 2% -60% of compound A, 5% -30% of wetting and dispersing agent, 0% -3% of stabilizer, and the balance is solvent;
  • the compound A is 2% -60%, solvent 2-15%, wetting and dispersing agent 1% -30%, stabilizer 0% -3%, and the balance is deionized water.
  • the water emulsion is based on a mass percentage of 2% -60% of compound A, 2-15% of solvent, 1% -30% of wetting and dispersing agent, 0.01% -1.5% of stabilizer, and the balance is deionized water. -;
  • the suspending agent based on the mass percentage content, is 2% -60% of compound A, 5% -30% of wetting and dispersing agent, 0.01% -1.5% of stabilizer, and the balance is deionized water;
  • the dispersible oil suspension agent based on the mass percentage content, is 2% -60% of compound A, 5% -30% of wetting and dispersing agent, 0.01% -1.5% of stabilizer, and the balance is dispersing medium oil;
  • the emulsifiable concentrate based on the mass percentage content, is 2% -60% of Compound A, 5% -30% of wetting and dispersing agent, 0.01% -1.5% of stabilizer, and the balance is solvent;
  • the compound A is 2% -60%, solvent 2-15%, wetting and dispersing agent 1% -30%, stabilizer 0.01% -1.5%, and the balance is deionized water.
  • the wetting and dispersing agents of the suspending agent are polyethylene oxide polyvinyl ethers, lignin sulfonates, high molecular carboxylates, naphthalene sulfonates, block copolymers, phosphates, and alkane
  • alkyl vinyl aryl phenyl ether, alkyl phenol polyoxy vinyl ether formaldehyde condensate sulfonate, or high molecular amphiphilic anionic non-ionic compound surfactant are polyethylene oxide polyvinyl ethers, lignin sulfonates, high molecular carboxylates, naphthalene sulfonates, block copolymers, phosphates, and alkane
  • the wetting and dispersing agents in the dispersible oil suspension, water emulsion, emulsifiable concentrate or microemulsion are sulfonates, carboxylates, phosphate salts, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene Ethers, fatty amine polyoxyethylene ethers, fatty acid polyoxyethylene ethers, acid alcohol esters and their polyoxyethylene ethers, alkyl polyglycol ethers, alkylphenyl polyglycol ethers, fatty amides and their polyoxyethylenes
  • ethers, alkanolamides and their polyoxyethylene ethers, block copolymers, sodium alkylnaphthalene sulfonate fatty alcohol polyoxyvinyl ether, sorbitan fatty acid ester polyoxyethylene ether are sulfonates, carboxylates, phosphate salts, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene Ethers, fatty
  • the wetting and dispersing agent in the suspending agent is a polyethylene oxide polyvinyl ether, a polymer carboxylate, and / or a phosphate ester surfactant.
  • the wetting and dispersing agent in the dispersible oil suspension, water emulsion, emulsifiable concentrate or microemulsion is a fatty alcohol polyoxyethylene ether and / or a block copolymer type surfactant.
  • polyethylene oxide polyvinyl ethers such as TENSIOFIX 35600 and the like, high molecular carboxylates and / or phosphates such as A4913 and the like.
  • the additives in the above formulations also include one or more of anionic surfactants, non-ionic surfactants, anionic non-composite surfactants, polymer surfactants, and dispersion media or carriers. It may also, but not necessarily, include thickeners, defoamers, preservatives, and pH adjusters.
  • Dispersion media include oils, organic solvents and water
  • Thickeners can be xanthan gum, gelatin, gum arabic, polyvinyl acetate, polyvinyl pyrrolidone, magnesium aluminum silicate, polyvinyl alcohol, polyethylene glycol, phenolic resin, shellac, hydroxymethyl cellulose, hydroxy One or more of ethyl cellulose, hydroxypropyl cellulose, methyl cellulose and sodium alginate can improve the physical delamination of the formulation to a certain extent.
  • the defoaming agent may be one or more of defoaming agents SAG1522, silicones, C8-10 fatty alcohols, phosphates, C10-20 saturated fatty acids (such as capric acid), and amides or others.
  • Preservatives can be sodium benzoate, carson (2-methyl-4-isothiazolin-3-one and (B) 5-chloro-2-methyl-4-isothiazolin-3-one), sorbus One or more of potassium acid, sodium dehydroacetate or others.
  • an organic solvent can also be used as an auxiliary solvent or an antifreeze additive.
  • the organic solvent may be selected from, but not limited to, aromatic hydrocarbons, chlorinated aromatic hydrocarbons, aliphatic hydrocarbons, chlorinated aliphatic hydrocarbons, and also vegetable oils and methyl-soluble fibers.
  • the above-mentioned preparation provided has good physical and chemical application performance, excellent dispersibility of the active component in the carrier, and at the same time, the active component is under the action of the selected stabilizer liquiritin, wetting and dispersing agent, and other suitable auxiliary agents.
  • the particle size is uniform, the dispersion stability is strong, and the drug effect is good; the use process of the preparation after dilution with water is stronger, its adhesion, penetration force is stronger, the drug effect is stronger.
  • the particle size of the liquid preparation is controlled to ensure its excellent control effect, and it is safe for crops.
  • Chiggeridae, Chiggeridae and so on have positive control effects.
  • the liquid preparation is applied at 10 to 5000 grams of active ingredient per hectare to the pests to be controlled or the growth medium thereof.
  • the liquid preparation can be diluted or sprayed directly with water by the user before use, or it can be used directly.
  • the invention uses the compound A with a lower melting point as an active substance to prepare a liquid preparation, and the obtained liquid preparation solves the problem that the existing dosage form will dissolve particles under the conditions of accelerated storage under the conditions of 54 ⁇ 2 ° C national standards.
  • the slightly increased particles will show an increase in the particle size D98, and the significantly increased particles will show a phenomenon such as gelatinization, resulting in the problem that the preparation product cannot be used.
  • the present invention can inhibit the increase of the particle size of the product by adding glycyrrhizin as a stabilizer to the liquid preparation under the condition of selecting and matching an appropriate auxiliary system, and giving a specific addition amount.
  • the interaction has the effect of suppressing the increase of the particle size in the liquid preparation.
  • the product stability is significantly improved, which guarantees its excellent control effect on acaricidal activity and the effect on crops. Safety.
  • the liquid preparation provided by the specific auxiliary agent of the present invention improves the wetting, spreading, dispersing, retaining and penetrating properties of the active ingredient on the growth medium, thereby increasing the retention amount of the active ingredient of the pesticide on the plant surface, extending the staying time, and improving the Epidermal penetrating ability, thereby increasing the biological activity of pesticides and reducing the dosage.
  • the liquid preparation of the present invention can control the particle size of the liquid preparation through a good auxiliary system, and has the characteristics of good dispersibility, high suspension rate, high biological activity, small dosage, low cost, resistance to rain erosion, low residue, low toxicity to humans and livestock, etc. .
  • the percentages and parts in the following formulations are by weight.
  • the active component Compound A is prepared in accordance with the prior art (content 93-99%) and added at a dosage of one hundred percent, the proportion of each component is weight percentage, and other raw materials are all commercially available products.
  • the structure of the used compound A is shown in Table 1.
  • compound A-1, 5%, D, 425, 5%, NNO, 3%, magnesium aluminum silicate 0.8%, xanthan gum 0.1%, and the remaining water can be made up to 100% to obtain a good dispersion 5 % Compound A-1 suspension.
  • Example 2-1 Formulation of 10% Compound A-2-1 Suspension Agent
  • compound A-2 10%, SK-24 5%, TENSIOFIX DB08 3%, magnesium aluminum silicate 0.6%, xanthan gum 0.1%, and the remaining water can be made up to 100% to obtain good dispersion.
  • compound A-2 10%, SK-24 5%, TENSIOFIX DB08 3%, glycyrrhizin 0.05%, magnesium aluminum silicate 0.6%, xanthan gum 0.1%, the remaining water is made up to 100%, that is, A 10% compound A-2-2 suspending agent with good dispersibility can be obtained.
  • compound A-3 15%, DB08 5% TENSIOFIX DB08 3%, magnesium aluminum silicate 1%, xanthan gum 0.1%, and the remaining water can be made up to 100% to obtain a good dispersion of 15% Compound A-6 suspension.
  • Example 4-1 Formulation of 15% Compound A-4-1 Suspension
  • compound A-4 15%, YUS-FS3000 5%, GYD07 3%, A4913 3%, magnesium aluminum silicate 1%, xanthan gum 0.1%, the remaining water can be made up to 100%, then you can get A good 15% compound A-4-1 suspending agent.
  • compound A-5 15%, AEO-3, 5%, NNO, 3%, magnesium aluminum silicate, 1%, xanthan gum, 0.1%, and the remaining water can be made up to 100% to obtain a good dispersion.
  • compound A-7 15%, GY-D07 4%, SP2728 3%, magnesium aluminum silicate 1%, xanthan gum 0.2%, and the remaining water can be made up to 100% to obtain a good dispersion.
  • 30% Compound A-4 suspension
  • Example 6-1 Formulation of a 10% compound A-4-1 dispersible oil suspension
  • compound A-1 10%, dispersant NP-10 5%, agricultural milk 1602, 4%, white carbon black 2%, methyl oleate make up to 100%, and then add them to the mixing tank and mix first. Coarse pulverization and homogenization under high shear, and then pumping into a sand mill for fine grinding, 10% Compound A-4-1 dispersible oil suspension can be obtained.
  • Example 6-2 Formulation of a 10% Compound A-4-2 dispersible oil suspension
  • compound A-1 10%, dispersant NP-10 5%, agricultural milk 1602 4%, white carbon black 2%, glycyrrhizin 0.5%, methyl oleate make up to 100%, and then add to the mixing tank Medium mixing, coarse crushing and homogenization after high shear, and then pumping into a sand mill for fine grinding, 10% compound A-4-2 dispersible oil suspension can be obtained.
  • Example 7 Formulation of a 15% Compound A-4 dispersible oil suspension
  • compound A-4 15%, dispersant NP-10 5%, agricultural milk 1601 4%, white carbon black 2%, methyl oleate make up to 100%, and then add them to the mixing tank and mix in sequence.
  • Coarse pulverization, homogenization under high shear, and then pumping into a sand mill for fine grinding can obtain 15% compound A-4 dispersible oil suspension agent.
  • Example 8 Formulation of 5% Compound A-1 Water Emulsion
  • compound A-1 5%, agricultural milk 0201B, 5%, agricultural milk 600% 2%, dimethylformamide 5%, and water to make up to 100% are added to the mixing kettle, stir and mix evenly, if necessary, use hot water The solution was heated and dissolved in a bath to obtain a 5% compound A-1 aqueous emulsion.
  • compound A-2 5%, agricultural milk 1602 # 5%, agricultural milk 6002%, solvent oil 200 # 5%, and water to 100% are added to the mixing kettle, stir and mix well, if necessary, use hot water
  • a 10% water emulsion of compound A-2 can be obtained by heating and dissolving in a bath.
  • compound A-3 10%, YUS-110 5%, YUS-D935 6%, cyclohexanone 10%, and water make up to 100% are added to the mixing kettle, stir and mix well, if necessary, use a hot water bath to heat When dissolved, a 10% aqueous emulsion of compound A-3 is obtained.
  • Example 11-1 Formulation of 15% Compound A-4-1 Water Emulsion
  • compound A-4, 15%, Atlox, 4838B, 4%, YUS-110, 7%, solvent oil 150 # 10%, and water up to 100% are added to the mixing kettle, stir and mix well, if necessary, use a hot water bath to heat Dissolve to obtain 15% Compound A-4-1 water emulsion.
  • Example 11-2 Formulation of 15% Compound A-4-2 Water Emulsion
  • compound A-4 15%, Atlox, 4838B, 4%, YUS-110, 7%, glycyrrhizin, 1%, solvent oil, 150 # 10%, water make up to 100%, add to the mixing kettle, stir and mix evenly, if necessary Heat and dissolve in a hot water bath to obtain 15% compound A-4-2 water emulsion.
  • Example 12-1 Formulation of 15% Compound A-4-3 Suspension
  • compound A-4, 15%, SPSC3, 5%, TENSIOFIX, 35600, 5%, A4913, 5%, magnesium aluminum silicate, 1%, xanthan gum, 0.1%, and the remaining water can be made up to 100% to obtain dispersion.
  • compound A-4 15%, YUS-FS3000 3%, TENSIOFIX 35600 5%, A4913 5%, magnesium aluminum silicate 1%, xanthan gum 0.1%, and the remaining water can be made up to 100%.
  • a good 15% compound A-4-4 suspension was obtained.
  • compound A-4 15%, NNO 5%, starch 10%, water 15%, and the balance of calcium carbonate is made up to 100%, and a 15% compound A-4 paste with good physical properties can be obtained.
  • compound A-4 15%, calcium lignin sulfonate 5%, NNO 3%, white carbon black 5%, the balance of light calcium carbonate can be supplemented to 100%, and 15% compound A with good physical properties can be obtained -4 Wettable powder.
  • the measurement of the data in Table 2 uses a laser particle size analyzer.
  • the meaning of particle size D98 is that 98% of the particle size in the system is below this value. Therefore, the smaller the value of D98, the smaller the particle size of the system.
  • the particle size changes from normal temperature to two storage conditions of 54 ⁇ 2 °C and 45 ⁇ 2 °C (refer to the manual development and use of FAO and WHO specific specifications), the smaller the change, the more effective the control of particle size is.
  • Example 1 9.88 49.88 35.21
  • Example 2-1 5.06 39.92 26.51
  • Example 2-2 5.11 7.51 5.54
  • Example 3 6.88 44.17 33.12
  • Example 4-1 3.96 21.99 14.81
  • Example 4-2 3.88 7.21 4.94 Comparative example 14.07 86.44 52.52
  • Example 5 5.11 37.21 25.63
  • Example 6 1.11 71.11 48.88
  • Example 6-2 3.94 5.66 4.92
  • Example 7 4.78 27.98 15.34
  • Example 8 5.21 28.99 18.33
  • Example 10 3.99 25.44 16.92
  • Example 11-1 3.21 22.19 17.66
  • Example 12-2 3.68 16.81 11.93
  • Example 12-3 3.22 6.99 4.21
  • Example 13 12.21 42.19 37.66
  • Example 14 18.66 49.89 38.09
  • the synergistic compatibility will disperse the active components in the carrier more evenly, especially the addition of glycyrrhizin will significantly improve the particle size control of the product system, and the biological activity of the formulation products formulated with the auxiliary system will be more prominent.
  • auxiliary systems and dispersing media also have a certain effect on the particle size of the dispersible oil suspending agent.
  • the particle size control also requires a specific auxiliary system, and the addition of glycyrrhizin also significantly improves the particle size control.
  • the synergy between the active components and the auxiliary system is achieved.
  • the formulation product prepared by the auxiliary system has good dispersibility, stable performance, and better control of particle size growth.
  • the particle size of the liquid preparation product obtained in the above embodiments can be controlled, which plays a vital role in various aspects such as the physical properties of the product, the long-term stability of the product, the applicability of the product, and the drug efficacy of the product.
  • Example 15 Biological Activity Test of C. cinnabarinus-1
  • Test agent 98% Compound A-4, Example 4-1, Example 4-2, Comparative Example.
  • Test conditions Pesticide laboratory, normal room temperature. In the pesticide observation room, the temperature, humidity, and light can be adjusted as required. Greenhouse, all-weather solar greenhouse.
  • Preparation of the medicinal solution An electronic analytical balance was used to accurately weigh the test agent, and the preparation was directly added with water to prepare a mother liquor of the required concentration. Compound A-4 was completely dissolved in the solvent, and then 0.1% Tween 80 water was used to prepare the mother liquor of the desired concentration. According to the experimental design, water was diluted into a series of chemical solutions with a certain concentration gradient.
  • Test method The potted seedling spray method was used to determine the activity of different batches of test samples against adult spider mite. Firstly, the adult spider mites of the same size were received on the leaves of kidney bean seedlings in the first pair of true leaves, and the cardinal number was counted after the adult mites were stabilized. Then the spray was uniformly sprayed in the order from low dose to high dose, 2mL per plant. , And set a blank control.
  • Example 4-2 It can be seen from Table 3 that the LC 50 value of Example 4-2 is the lowest and the activity is the best. Corresponding to Table 2, the particle size is smaller and the particle size growth control is better. The biological activity of Example 4-1 was slightly worse than that of Example 4-2, but was significantly better than that of Compound A-4. From this, it can be judged that after adding glycyrrhizin, the biological activity of the suspension system is improved, and the LC 50 value can be further reduced. From the LC 50 of the comparative example, it can be seen that on the basis of the unsuitability of the auxiliary system, as shown in Table 2, the particle size itself has a large numerical value, and the increase in particle size is also large. Even if it is prepared as a formulation, because The control of the particle size is not ideal, and no better efficacy is obtained, and its LC 50 value is even higher than that of the original drug.
  • the liquid preparation product of the compound A whether it is a suspending agent, an aqueous emulsion, a dispersible oil suspending agent, etc., can only ensure the exertion of the drug effect under the condition of good synergistic effect of the auxiliary system. Avoid the disadvantages caused by the conventional preparation mentioned in the patent CN105541682A, and the control of the particle size plays an important role in the exertion of the efficacy of the liquid preparation.
  • Test agent 98% of compound A-4, Example 12-1, Example 12-2, Example 12-3, Example 13, Example 14.
  • Test conditions same as in Example 15. (Pesticide laboratory, normal room temperature. Pesticide observation room, temperature, humidity, and light can be adjusted as needed. Greenhouse, all-weather greenhouse.)
  • Chemical solution preparation same as in Example 15. (Accurately weigh the test agent with an electronic analytical balance. The preparation is directly added with water to prepare the mother liquor of the required concentration. Compound A-4 is first completely dissolved in the solvent, and then 0.1% Tween 80 water is used to prepare the mother liquor of the required concentration. Designed according to the test. A series of chemical solutions diluted to a certain concentration gradient with water.)
  • Test method same as in Example 15. (The potted seedling spray method was used to determine the activity of different batches of test samples against adult spider mites. The spider mite adults of the same size were first connected to the leaves of kidney bean seedlings in the first pair of true leaf flattening stages, and the adult mites were stable. After counting the cardinal numbers; then spray uniformly in the order of low dose to high dose of the experimental design, 2mL per plant, and set a blank control.)
  • Example 16 Three suspending agent samples were prepared according to a similar technical scheme. From the obtained data, it can be seen that the suspending agent samples prepared by a suitable auxiliary system have excellent biological activity under controlled particle size conditions.
  • LC 50 They are 0.7396 mg / L, 0.7354 mg / L, and 0.5697 mg / L, which are significantly superior to Compound A-4LC 50 at 0.8202.
  • Example 12-3 in which glycyrrhizin was added had a more prominent effect than the others.
  • Example 13 and Example 14 It can be seen from Example 13 and Example 14 that it is not possible to prepare pesticide formulations with good efficacy according to technical schemes well known in the industry.
  • the efficacy of Examples 13 and 14 is prepared according to conventional methods. , Significantly worse than the compound itself and other examples in the present invention.
  • the “compositions prepared in the prior art are prepared in a known manner, for example, in the presence of an optional surfactant, the solvent is diluted or dissolved by a solvent medium and / or a solid diluent. "There are certain technical drawbacks, that is, if you want to achieve a suitable particle size and even good drug effect, you need to obtain the technical solution mentioned in the present invention to meet the demand for pesticide products in the field. .
  • the data in Tables 3 and 4 are the indoor efficacy results of the samples, not the actual field application results.
  • the evaluation of the activity of a compound for indoor medicinal effect is to use a large amount of Tween water to dilute it under the condition of dissolving a polar solvent, which is equivalent to increasing the amount of surfactant, which is far more than the formulation.
  • the amount of the surfactant used greatly reduces the surface tension of the compound medicinal solution. From this point of view, the efficacy is improved, not the efficacy of the compound itself.
  • the compounds in the above cases cannot be really applied to the field.
  • the agriculturally applicable dosage form prepared by Compound A-4 has far-reaching prevention and control effects on crops.
  • the spider mite Tetranychus in the Tetranyidae family mentioned in the above examples can be inferred from the compound A invention patent CN105541682A.
  • the preparation has a positive control effect on the spider mite family (two-spotted spider mite, apple claw mite, citrus claw mite, etc.), chigger mite, and nymphalidae.
  • the preparation of the compound A-4 in other dosage forms will also have excellent control effects.
  • other structures A- 1. A-2 and A-3 were tested for biological activity using the same preparation method in the examples. What is not described in detail in this specification belongs to the prior art known to those skilled in the art.

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Abstract

本发明属于杀螨剂领域，涉及一种含联苯类化合物的液体制剂及其应用。含联苯类化合物的液体制剂，以化合物A为活性组分，并配以至少一种载体和至少一种助剂，液体制剂的活性组分重量百分含量为0.1-99％；本发明液体制剂通过良好助剂体系使得液体制剂粒径得以控制，且分散性好、悬浮率高、生物活性高，使用剂量小、成本低、耐雨水冲刷、残留低、对人畜低毒等特点。

Description

一种含联苯类化合物的液体制剂及其应用 技术领域
本发明属于杀螨剂领域，涉及一种含联苯类化合物的液体制剂及其应用。
背景技术
在中国发明专利CN 105541682 A公开的联苯类化合物(以下简称化合物A)有较优异的杀螨防治效果，具有广阔的市场应用前景。化合物A的结构如下：
Figure PCTCN2019092162-appb-000001
如前述发明专利CN 105541682 A中提及，该化合物的使用形式可以是干粉、可湿性粉剂、乳油、微乳剂、糊剂、颗粒剂、溶液、悬浮剂等，但专利中记载化合物的使用形式是以已知方式制备的，例如任选在表面活性剂的存在下，通过用溶剂介质和/或固体稀释剂稀释或溶解活性物质，但本领域所知化合物使用类型的选择取决于具体的应用。同时在实际开发农药制剂产品过程中发现，前述专利中提及的可以制备为剂型的形式是普遍意义的可施用制备，无法控制产品的粒度，而且经过大量数据验证，此种普遍意义的可施用制备，粒径的增长是很明显的，进而使得药效受到明显影响，甚至导致无法使用，产品出现膏化、絮凝等问题直接作为不合格产品。而且化合物A的熔点在50～60℃，这对于液体制剂来说，是一个典型的弊端。如行业内所熟知，悬浮剂的制备条件要求如下：熔点大于60℃，水中溶解度小于200mg/L，且在水溶液中稳定。据目前报道，尚有部分化合物的熔点在60℃左右，如二甲戊灵熔点为54℃～58℃，腈菌唑熔点63-68℃，虽然可一定程度上满足制备悬浮剂的条件，但因其熔点较低，在国家农药制剂标准中的热贮加速试验中容易出现物性的改变，如膏化、絮凝、析晶、粒径增大等现象，转入常温放置后，粒径还会进一步增长。在这种情况下，农药液体制剂产品，包括但不限于悬浮剂、水乳剂、微乳剂、可溶液剂等，均会出现不合格。在实际应用过程中，由于粒径的增长，使药效受到明显影响，甚至导致无法使用。因此，开发适合于该活性组分，合格性能，粒径不显著增加的农药液体制剂是具有非常重大意义。
发明内容
本发明目的在于提供一种含联苯类化合物的液体制剂及其应用。
为实现上述目的，本发明采用技术方案为：
一种含联苯类化合物的液体制剂，以化合物A为活性组分，并配以至少一种载体和至少一种助剂，液体制剂的活性组分重量百分含量为0.1-99％；其中， 化合物A结构式如下，
Figure PCTCN2019092162-appb-000002
式中，R 1、R 2各自独立地选自氢、C 1-C 8烷基、卤代C 1-C 8烷基、C 2-C 8烯基、卤代C 2-C 8烯基、C 2-C 8炔基、卤代C 2-C 8炔基、氰基C 1-C 8烷基或氰基卤代C 1-C 8烷基；m、n各自独立地选自0、1或2。
所述杀螨剂液体剂型为可溶液剂、油剂、展膜油剂、可分散液剂、水乳剂、油乳剂、乳油、微乳剂、悬浮剂、微囊悬浮剂、油悬浮剂、可分散油悬浮剂或超低溶量液剂。
所述杀螨剂剂型为水乳剂、悬浮剂、可分散油悬浮剂、乳油或微乳剂。
所述液体制剂中助剂还包括稳定剂；其中稳定剂为甘草苷。
所述水乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-20％、润湿分散剂1％-30％，稳定剂0％-3％，余量为去离子水；
所述悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0％-3％，余量为去离子水；
所述可分散油悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0％-3％，余量为分散介质油；
所述乳油，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0％-3％，余量为溶剂；
所述微乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-15％、润湿分散剂1％-30％，稳定剂0％-3％，余量为去离子水。
优选所述水乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-15％、润湿分散剂1％-30％，稳定剂0.01％-1.5％，余量为去离子水-；
所述悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0.01％-1.5％，余量为去离子水；
所述可分散油悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0.01％-1.5％，余量为分散介质油；
所述乳油，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0.01％-1.5％，余量为溶剂；
所述微乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-15％、润湿分散剂1％-30％，稳定剂0.01％-1.5％，余量为去离子水。
所述悬浮剂的润湿分散剂为聚环氧乙烷聚乙烯基醚类、木质素磺酸盐、高分子羧酸盐、萘磺酸盐类、嵌段共聚物类、磷酸酯类、烷基乙烯芳基苯基醚、烷基酚聚氧乙烯基醚甲醛缩合物磺酸盐或高分子双亲型阴非离子复配表面活性剂中 的一种或几种；
所述可分散油悬浮剂、水乳剂、乳油或微乳剂中的润湿分散剂为磺酸盐类、羧酸盐类、磷酸酯盐类、脂肪醇聚氧乙烯醚、烷基酚聚氧乙烯醚、脂肪胺聚氧乙烯醚、脂肪酸聚氧乙烯醚、酸醇酯及其聚氧乙烯醚、烷基聚乙二醇醚、烷基苯基聚乙二醇醚、脂肪酰胺及其聚氧乙烯醚、烷醇酰胺及其聚氧乙烯醚、嵌段共聚物、烷基萘磺酸钠脂肪醇聚氧乙烯基醚、失水山梨醇脂肪酸酯聚氧乙烯基醚中的一种或几种。
优选所述悬浮剂中的润湿分散剂为聚环氧乙烷聚乙烯基醚类、高分子羧酸盐和/或磷酸酯类表面活性剂。
所述可分散油悬浮剂、水乳剂、乳油或微乳剂中的润湿分散剂为脂肪醇聚氧乙烯醚和/或嵌段共聚物类表面活性剂。
所述聚环氧乙烷聚乙烯基醚类如TENSIOFIX 35600等、高分子羧酸盐和/或磷酸酯类如A4913等。
上述制剂中助剂还包括阴离子表面活性剂、非离子表面活性剂、阴非复配表面活性剂、高分子表面活性剂中的一种或几种，以及分散介质或载体等，除此之外还可以但非必要包括增稠剂、消泡剂、防腐剂、pH调节剂。
分散介质包括油类、有机溶剂及水；
增稠剂可为黄原胶、明胶、阿拉伯树胶、聚乙烯醋酸酯、聚乙烯吡咯烷酮、硅酸镁铝、聚乙烯醇、聚乙二醇、酚醛树脂、虫胶、羟甲基纤维素、羟乙基纤维素、羟丙基纤维素、甲基纤维素和海藻酸钠中的一种或几种，可在一定程度上改善制剂的物理分层情况。
消泡剂可为消泡剂SAG1522、硅酮类、C8～10脂肪醇、磷酸酯类、C10～20饱和脂肪酸类(如癸酸)及酰胺或其他中的一种或几种。
防腐剂，可为苯甲酸钠、卡松(2－甲基-4-异噻唑啉-3-酮和(B)5－氯-2-甲基-4-异噻唑啉-3-酮)、山梨酸钾、脱氢乙酸钠或其他中的一种或几种。
上述制备相应剂型，在水用作溶剂或稀释剂时，有机溶剂也可用作辅助溶剂或防冻添加剂。
有机溶剂可选自但不限于芳烃、氯代芳烃、脂族烃、氯代脂族烃，还有植物油和甲基溶纤维。
所述提供的上述制剂，物理化学应用性能良好，活性组分在载体中的分散性优异，且同时活性组分在所筛选出稳定剂甘草苷、润湿分散剂以及匹配的其它助剂作用下，颗粒粒径均匀、分散稳定性强、药效良好；使得制剂用水稀释后的使用过程中，其附着、渗透力更强大，药效的传导作用更强。
一种含联苯类化合物液体制剂的应用，所述液体制剂在作为植物杀螨剂中的应用。
所述施用的液体剂型后，通过液体制剂粒径的控制保证了其优异的防治效果，对作物安全，可以针对叶螨科(二斑叶螨、朱砂叶螨、苹果全爪螨、柑橘全爪螨等)、瘿螨科、跗线螨科等具有积极防治效果。
所述液体制剂以10～5000克有效成分/公顷施于需要控制的虫害或其生长的介质上。
液体制剂在使用前可以由使用者经稀释或直接兑水喷雾，也可以直接使用。
本发明所具有的优点：
本发明以熔点较低的化合物A为活性物质制备为液体制剂，所得液体制剂解决了现有剂型在处于热贮加速条件54±2℃国家标准规定条件下，活性物质会出现粒子的溶解，粒径的增长聚集，轻微增长的粒子会表现出粒径D98的增加，显著增长的粒子会表现出膏化等现象，导致制剂产品无法使用的问题。进而本发明通过在选择搭配合适的助剂体系条件下，在液体制剂中加入作为稳定剂的甘草苷，并给出特定的添加量，可以抑制产品粒径的增长，甘草苷与化合物A结构的相互作用，起到抑制液体制剂中粒径增大的效果，甘草苷的加入，粒径得到控制后，产品稳定性有明显提升，保证了其对杀螨活性的优异的防治效果，且对作物安全。
本发明特定助剂配置的液体制剂改善了有效成分在生长介质上的润湿、展布、分散、滞留和渗透性能，从而增加农药有效成分在植物表面的滞留量、延长滞留时间和提高对植物表皮穿透能力，进而提高农药的生物活性，降低使用剂量。本发明液体制剂通过良好助剂体系使得液体制剂粒径得以控制，且分散性好、悬浮率高、生物活性高，使用剂量小、成本低、耐雨水冲刷、残留低、对人畜低毒等特点。
具体实施方式
以下具体实施例用于进一步详细说明本发明，但本发明绝非限于这些例子，业内人士熟知的方法，都包含在本发明的范围内。
下述配方中百分比和份数均以重量计。活性组分化合物A为依照现有技术的记载制备获得(含量93-99％)折百后剂量加入，各组分比例为重量百分比，其他各原料均为市售品。所使用化合物A的结构根据表1所示。
Figure PCTCN2019092162-appb-000003
表1化合物A的结构
组合物 R 1 R 2 m n
A-1 CH 2CF 3 CH 2CF 3 0 1
A-2 CH 2CF 3 CH 2CF 3 1 1
A-3 CH 2CF 3 CH 2CF 3 1 2
A-4 CH 2CF 3 CH 2CF 3 0 0
制剂配方实施例
实施例1. 5％化合物A-1悬浮剂的配制
按配方要求，化合物A-1 5％、D 425 5％、NNO 3％、硅酸镁铝0.8％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的5％化合物A-1悬浮剂。
实施例2—1. 10％化合物A-2-1悬浮剂的配制
按配方要求，化合物A-2 10％、SK-24 5％、TENSIOFIX DB08 3％、硅酸镁铝0.6％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的10％化合物A-2-1悬浮剂。
实施例2—2 10％化合物A-2-2悬浮剂的配制
按配方要求，化合物A-2 10％、SK-24 5％、TENSIOFIX DB08 3％、甘草苷0.05％、硅酸镁铝0.6％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的10％化合物A-2-2悬浮剂。
实施例3. 15％化合物A-3悬浮剂的配制
按配方要求，化合物A-3 15％、DB08 5％TENSIOFIX DB08 3％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-6悬浮剂。
实施例4-1. 15％化合物A-4-1悬浮剂的配制
按配方要求，化合物A-4 15％、YUS-FS3000 5％、GYD07 3％、A4913 3％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-4-1悬浮剂。
实施例4-2 15％化合物A-4-2悬浮剂的配制
按配方要求，化合物A-4 15％、YUS-FS3000 5％、GYD07 3％、A4913 3％、甘草苷0.05％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-4-2悬浮剂。
对比例1. 15％化合物A-4悬浮剂的配制
按配方要求，化合物A-5 15％、AEO-3 5％、NNO 3％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-4悬浮剂。
实施例5. 30％化合物A-4悬浮剂的配制
按配方要求，化合物A-7 15％、GY-D07 4％、SP2728 3％、硅酸镁铝1％、黄原胶0.2％，将余量水补足至100％，即可得到分散性良好的30％化合物A-4悬浮剂。
实施例6-1. 10％化合物A-4-1可分散油悬浮剂的配制
按配方要求，化合物A-1 10％、分散剂NP-10 5％、农乳1602 4％、白炭黑2％、油酸甲酯补足至100％，依次加入到混合罐中混合，先经过高剪切进行粗粉碎、匀化，然后抽入到砂磨机中进行细磨，即可得到10％化合物A-4-1可分散油悬浮剂。
实施例6-2. 10％化合物A-4-2可分散油悬浮剂的配制
按配方要求，化合物A-1 10％、分散剂NP-10 5％、农乳1602 4％、白炭黑2％、 甘草苷0.5％，油酸甲酯补足至100％，依次加入到混合罐中混合，先经过高剪切进行粗粉碎、匀化，然后抽入到砂磨机中进行细磨，即可得到10％化合物A-4-2可分散油悬浮剂。
实施例7. 15％化合物A-4可分散油悬浮剂的配制
按配方要求，化合物A-4 15％、分散剂NP-10 5％、农乳1601 4％、白炭黑2％、油酸甲酯补足至100％，依次加入到混合罐中混合，先经过高剪切进行粗粉碎、匀化，然后抽入到砂磨机中进行细磨，即可得到15％化合物A-4可分散油悬浮剂。
实施例8. 5％化合物A-1水乳剂的配制
按配方要求，化合物A-1 5％、农乳0201B 5％、农乳600 2％、二甲基甲酰胺5％、水补足至100％加入混合釜中，搅拌混合均匀，必要时用热水浴加热溶解，即可得到5％化合物A-1水乳剂。
实施例9. 10％化合物A-2水乳剂的配制
按配方要求，化合物A-2 5％、农乳1602#5％、农乳600 2％、溶剂油200#5％、水补足至100％加入混合釜中，搅拌混合均匀，必要时用热水浴加热溶解，即可得到10％化合物A-2水乳剂。
实施例10. 10％化合物A-3水乳剂的配制
按配方要求，化合物A-3 10％、YUS-110 5％、YUS-D935 6％、环己酮10％、水补足至100％加入混合釜中，搅拌混合均匀，必要时用热水浴加热溶解，即可得到10％化合物A-3水乳剂。
实施例11-1. 15％化合物A-4-1水乳剂的配制
按配方要求，化合物A-4 15％、Atlox 4838B 4％、YUS-110 7％、溶剂油150#10％、水补足至100％加入混合釜中，搅拌混合均匀，必要时用热水浴加热溶解，即可得到15％化合物A-4-1水乳剂。
实施例11-2. 15％化合物A-4-2水乳剂的配制
按配方要求，化合物A-4 15％、Atlox 4838B 4％、YUS-110 7％、甘草苷1％、溶剂油150#10％、水补足至100％加入混合釜中，搅拌混合均匀，必要时用热水浴加热溶解，即可得到15％化合物A-4-2水乳剂。
实施例12-1. 15％化合物A-4-3悬浮剂的配制
按配方要求，化合物A-4 15％、SPSC3 5％、TENSIOFIX 35600 5％、A4913 5％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-4-3悬浮剂。
实施例12-2. 15％化合物A-4-4悬浮剂的配制
按配方要求，化合物A-4 15％、YUS-FS3000 3％、TENSIOFIX 35600 5％、A4913 5％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-4-4悬浮剂。
实施例12-3. 15％化合物A-4-5悬浮剂的配制
按配方要求，化合物A-4 15％、YUS-FS3000 3％、TENSIOFIX 35600 5％、A4913 5％、甘草苷0.05％、硅酸镁铝1％、黄原胶0.1％，将余量水补足至100％，即可得到分散性良好的15％化合物A-4-5悬浮剂。
实施例13. 15％化合物A-4糊剂的配制
按配方要求，化合物A-4 15％、NNO 5％、淀粉10％、水15％，余量碳酸钙补至100％，即可得到物性良好的15％化合物A-4糊剂。
实施例14. 15％化合物A-4可湿性粉剂的配制
按配方要求，化合物A-4 15％、木质素磺酸钙5％、NNO 3％、白炭黑5％，余量轻质碳酸钙补至100％，即可得到物性良好的15％化合物A-4可湿性粉剂。
分别测定上述各实施例获得液体制剂的常温粒径、45±2℃、54±2℃下的热贮粒径，详见表2。
表2中数据的测定采用激光粒度仪，粒径D98的含义为体系中98％的粒子大小在该数值以下，所以D98的数值越小，证明体系的粒径越小。而粒径从常温到两种贮存条件54±2℃与45±2℃(参考Manual on development and use of FAO and WHO specifications for pesticides标准)下，变化越小，证明对粒径的控制更有效。
表2粒径(D98μm)控制影响
实施例 常温粒径D98 54度14d粒径D98 45度42d粒径D98
实施例1 9.88 49.88 35.21
实施例2-1 5.06 39.92 26.51
实施例2-2 5.11 7.51 5.54
实施例3 6.88 44.17 33.12
实施例4-1 3.96 21.99 14.81
实施例4-2 3.88 7.21 4.94
对比例 14.07 86.44 52.52
实施例5 5.11 37.21 25.63
实施例6-1 11.11 71.11 48.88
实施例6-2 3.94 5.66 4.92
实施例7 4.78 27.98 15.34
实施例8 5.21 28.99 18.33
实施例9 4.92 30.01 19.97
实施例10 3.99 25.44 16.92
实施例11-1 3.21 22.19 17.66
实施例11-2 2.88 5.37 3.99
实施例12-1 3.88 20.09 13.71
实施例12-2 3.68 16.81 11.93
实施例12-3 3.22 6.99 4.21
实施例13 12.21 42.19 37.66
实施例14 18.66 49.89 38.09
由表2可以看出，对于实施例1-6、12-1—12-3的悬浮剂来说，不同助剂体系对化合物A制备悬浮剂的粒度有一定影响。在特定的助剂体系下对制剂的粒径控制有明显改善，而对于制剂中加入甘草苷后，如实施例2-2中甘草苷的加入明显可以看出，在两种加速热贮条件下，加入甘草苷后的悬浮剂对于粒径的控制都有显著提高和改善；进而可见加入甘草苷后的悬浮剂制剂的体系，与现有技术相比，实现活性组分与助剂体系之间的协同配伍，将活性组分在载体中分散的更均匀，尤其甘草苷的加入使产品体系的粒径控制有明显改善，用该助剂体系配制的制剂产品生物活性更加突出。
对于实施例7、8可分散油悬浮剂来说，不同助剂体系及分散介质，对于可分散油悬浮剂的粒度也存在一定影响。粒径的控制也需要特定的助剂体系，且甘草苷的加入，也对粒径的控制有明显的改善，与现有技术相比，实现活性组分与助剂体系之间的协同，用该助剂体系配制的制剂产品，具有分散性好、性能稳定、且粒径增长控制较佳。且其稀释液在靶标上沉积量大、附着性强、渗透力更强大，生物活性更突出，从而提高有效成分利用率，进而达到了减少用药次数和用药量的目的，而且对环境的污染小，对人、畜、鸟类及有益生物安全，更有利于保护生态平衡。
对于实施例9-11的水乳剂来说，不同助剂体系对粒径的控制有一定影响，且甘草苷的加入，可以很好的控制在两种贮存条件下粒径的增长。
对于实施例13及实施例14的可湿性粉剂来说，其常温样品的粒径较大。可以说明在现有技术中提及的某种结构物质，可以制备常规施用剂型是存在一定技术缺陷的，即想要达到适合的粒径，甚至良好的药效，需要制剂技术的辅佐。
综上可见上述实施例获得液体制剂产品粒径得以控制，对于产品的物理性能、产品的持久稳定性、产品的适用性、产品的药效等各个方面都起到至关重要的作用。
同时在甘草苷特定加入后其与化合物A的结构存在相互作用，可以有效控制化合物A结构在贮存条件变化的情况下，杂质或晶型的改变，从而控制粒径的增长。本发明中加入该类物质，获得了意想不到的结果，解决了现有技术中低熔点化合物粒径控制的问题，从而得到了性能优秀的制剂配方，粒径小，生物性能优良。
生物活性实施例
为了验证粒径控制后，对于药效的影响，开展了以下生物活性试验，试验中对比了实施例4-1、实施例4-2、对比例以及化合物A，对朱砂叶螨的生物活性。实施例15朱砂叶螨生物活性试验-1
供试药剂：98％化合物A-4、实施例4-1、实施例4-2、对比例制剂。
试验条件：杀虫剂实验室，正常室温。杀虫剂观察室，温度、湿度、光照按需可调节。温室，全天候日光温室。
药液配制：用电子分析天平准确称取供试药剂，制剂直接加水配制成所需浓度母液，化合物A-4先以溶剂完全溶解，再用0.1％吐温80水配制成所需浓度母液，按试验设计用水分别稀释成一定浓度梯度的系列药液。
试验方法：采用盆栽幼苗喷雾法测定不同批次的供试样品对朱砂叶螨成螨的活性大小。首先将大小一致的朱砂叶螨成螨接到处于第一对真叶平展期的菜豆幼苗叶片上，待成螨稳定后计数基数；然后按试验设计从低剂量到高剂量的顺序均匀喷雾，每株2mL，另设空白对照。
调查方法：将处理后的试材置于一定条件的观察室中，定期调查死活成螨数，计算死亡率，并用DPS软件，计算毒力回归方程式、LC 50值及95％置信限。
表3样品对朱砂叶螨成螨室内毒力测定
Figure PCTCN2019092162-appb-000004
由表3可以看出，实施例4-2的LC 50值最低，活性最佳，对应表2中粒度较小，且粒度增长控制较佳。实施例4-1的生物活性略差于实施例4-2，但明显优于化合物A-4。由此，可以判断出，加入甘草苷后对悬浮体系生物活性有所提高，而且LC 50值还可进一步降低。从对比例的LC 50可以看出，在助剂体系不适合的基础上，如表2所示，其粒径自身数值大，且粒径的增长幅度也较大，即便是制备为制剂，由于粒径的控制不理想，也未获得较佳的药效，其LC 50值甚至高于原药。
由此，可以推断出该化合物A的液体制剂产品，无论是悬浮剂、水乳剂、可分散油悬浮剂等，在助剂体系的协同作用良好的条件下，才能够保证药效的发挥，才能避免对比文件专利CN 105541682 A中提及的常规制备所带来的弊端，而且粒径的控制对于液体制剂药效的发挥起到重要作用。
实施例16朱砂叶螨生物活性试验-2
供试药剂：98％化合物A-4、实施例12-1、实施例12-2、实施例12-3、实施例13、实施例14。
试验条件：同实施例15。(杀虫剂实验室，正常室温。杀虫剂观察室，温度、湿度、光照按需可调节。温室，全天候日光温室。)
药液配制：同实施例15。(用电子分析天平准确称取供试药剂，制剂直接加水配制成所需浓度母液，化合物A-4先以溶剂完全溶解，再用0.1％吐温80水配制成所需浓度母液，按试验设计用水分别稀释成一定浓度梯度的系列药液。)
试验方法：同实施例15。(采用盆栽幼苗喷雾法测定不同批次的供试样品对 朱砂叶螨成螨的活性大小。首先将大小一致的朱砂叶螨成螨接到处于第一对真叶平展期的菜豆幼苗叶片上，待成螨稳定后计数基数；然后按试验设计从低剂量到高剂量的顺序均匀喷雾，每株2mL，另设空白对照。)
调查方法：将处理后的试材置于一定条件的观察室中，定期调查死活成螨数，计算死亡率，并用DPS软件，计算毒力回归方程式、LC 50值及95％置信限。
表4样品对朱砂叶螨成螨室内毒力测定
Figure PCTCN2019092162-appb-000005
本轮生物活性验证目的同实施例15，仅为进一步确认本发明技术方案而进行。
实施例16按照相似技术方案制备了悬浮剂样品三个，从获得数据中可以看出，适合的助剂体系制备的悬浮剂样品，在粒径可控条件下，生物活性均较优秀，LC 50分别为0.7396mg/L、0.7354mg/L、0.5697mg/L，明显优异于化合物A-4LC 50为0.8202。其中，加入甘草苷的实施例12-3，与其他相比，有更加突出的效果。
从实施例13、实施例14可以看出，并不是按照行业内熟知的技术方案，就可以制备为药效良好的农药制剂，按照常规手段，制备出的实施例13、实施例14的药效，明显差于化合物本身以及本发明中的其他实施例。结合粒径对比试验，再一次说明，现有技术中提及的“组合物是已知方式制备的，例如任选表面活性剂的存在下，通过溶剂介质和/或固体稀释剂稀释或溶解活性物就可以获得对应制剂”是存在一定技术缺陷的，即想要达到适合的粒径，甚至良好的药效，需要本发明中提及的技术方案获得，以满足农药产品在田间可施用的需求。
需要说明的是，表3、表4中的数据为样品的室内药效结果，并非实际田间应用结果。根据本技术领域内所熟知，室内药效的化合物活性评价是在极性溶剂溶解条件下，采用大量吐温水稀释使用，这就相当于加大了表面活性剂用量，该用量远超于配制制剂所使用的表面活性剂用量，从而大大降低了化合物药液的表面张力，从这一角度来提高药效，而并非化合物本身的药效。上述情况下的化合物是无法真正应用于田间的，一方面出于环保要求，不允许大量极性溶剂流入田间；另一方面是出于可实现的技术现状，主要由于大量表面活性剂无法加入到制剂体系中的现实问题。因此，表3、表4中的药效数据在实际田间应用中，化合物的活性会更加差于制剂活性。即本发明的技术方案获得技术效果势必更加显著。
化合物A-4制备成的农业上可施用的剂型，对作物的防治范围远不止上述实施例中所提及的叶螨科的朱砂叶螨，根据化合物A发明专利CN 105541682 A记载，可以推测出该化合物的制剂对叶螨科(二斑叶螨、苹果全爪螨、柑橘全爪螨等)、瘿螨科、跗线螨科等具有积极防治效果。根据几个生物活性中所使用剂型，可以合理推测，该化合物A-4制备为其他剂型，也会具有优异的防效，按照上述实施例生物活性测定方法，可以对该化合物的其他结构A-1、A-2、A-3采用实施例中的相同制备方法，进行生物活性试验。本说明书中未作详细描述的内容属于本领域专业技术人员公知的现有技术。

Claims (10)

  1. 一种含联苯类化合物的液体制剂，以化合物A为活性组分，并配以至少一种载体和至少一种助剂，其特征在于：液体制剂的活性组分重量百分含量为0.1-99％；其中，化合物A结构式如下，
    Figure PCTCN2019092162-appb-100001
    式中，R 1、R 2各自独立地选自氢、C 1-C 8烷基、卤代C 1-C 8烷基、C 2-C 8烯基、卤代C 2-C 8烯基、C 2-C 8炔基、卤代C 2-C 8炔基、氰基C 1-C 8烷基或氰基卤代C 1-C 8烷基；m、n各自独立地选自0、1或2。
  2. 按权利要求1所述含联苯类化合物的液体制剂，其特征在于:所述杀螨剂液体剂型为可溶液剂、油剂、展膜油剂、可分散液剂、水乳剂、油乳剂、乳油、微乳剂、悬浮剂、微囊悬浮剂、油悬浮剂、可分散油悬浮剂或超低溶量液剂。
  3. 按权利要求2所述含联苯类化合物的液体制剂，其特征在于:所述杀螨剂剂型为水乳剂、悬浮剂、可分散油悬浮剂、乳油或微乳剂。
  4. 按权利要求1-3任意一项所述含联苯类化合物的液体制剂，其特征在于:所述液体制剂中助剂还包括稳定剂；其中稳定剂为甘草苷。
  5. 按权利要求2所述含联苯类化合物的液体制剂，其特征在于:所述水乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-20％、润湿分散剂1％-30％，稳定剂0％-3％，余量为去离子水；
    所述悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0％-3％，余量为去离子水；
    所述可分散油悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0％-3％，余量为分散介质油；
    所述乳油，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0％-3％，余量为溶剂；
    所述微乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-15％、润湿分散剂1％-30％，稳定剂0％-3％，余量为去离子水。
  6. 按权利要求5所述含联苯类化合物的液体制剂，其特征在于:
    所述水乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-15％、润湿分散剂1％-30％，稳定剂0.01％-1.5％，余量为去离子水-；
    所述悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0.01％-1.5％，余量为去离子水；
    所述可分散油悬浮剂，按质量百分比含量计，化合物A 2％-60％、润湿分 散剂5％-30％，稳定剂0.01％-1.5％，余量为分散介质油；
    所述乳油，按质量百分比含量计，化合物A 2％-60％、润湿分散剂5％-30％，稳定剂0.01％-1.5％，余量为溶剂；
    所述微乳剂，按质量百分比含量计，化合物A 2％-60％、溶剂2-15％、润湿分散剂1％-30％，稳定剂0.01％-1.5％，余量为去离子水。
  7. 按权利要求5或6所述含联苯类化合物的液体制剂，其特征在于:
    所述悬浮剂的润湿分散剂为聚环氧乙烷聚乙烯基醚类、木质素磺酸盐、高分子羧酸盐、萘磺酸盐类、嵌段共聚物类、磷酸酯类、烷基乙烯芳基苯基醚、烷基酚聚氧乙烯基醚甲醛缩合物磺酸盐或高分子双亲型阴非离子复配表面活性剂中的一种或几种；
    所述可分散油悬浮剂、水乳剂、乳油或微乳剂中的润湿分散剂为磺酸盐类、羧酸盐类、磷酸酯盐类、脂肪醇聚氧乙烯醚、烷基酚聚氧乙烯醚、脂肪胺聚氧乙烯醚、脂肪酸聚氧乙烯醚、酸醇酯及其聚氧乙烯醚、烷基聚乙二醇醚、烷基苯基聚乙二醇醚、脂肪酰胺及其聚氧乙烯醚、烷醇酰胺及其聚氧乙烯醚、嵌段共聚物、烷基萘磺酸钠脂肪醇聚氧乙烯基醚、失水山梨醇脂肪酸酯聚氧乙烯基醚中的一种或几种。
  8. 按权利要求7所述含联苯类化合物的液体制剂，其特征在于:所述悬浮剂中的润湿分散剂为聚环氧乙烷聚乙烯基醚类、高分子羧酸盐和/或磷酸酯类表面活性剂；
    所述可分散油悬浮剂、水乳剂、乳油或微乳剂中的润湿分散剂为脂肪醇聚氧乙烯醚和/或嵌段共聚物类表面活性剂。
  9. 一种权利要求1所述含联苯类化合物的液体制剂的应用，其特征在于:所述制剂作为农用杀螨剂的应用。
  10. 按权利要求9所述含联苯类化合物的液体制剂的应用，其特征在于:所述制剂以10～5000克有效成分/公顷施于需要控制的螨害或其生长的介质上。
PCT/CN2019/092162 2018-08-30 2019-06-21 一种含联苯类化合物的液体制剂及其应用 WO2020042730A1 (zh)

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