Kasugamycin organic acid salt pesticide mixture composition and application

Abstract

According to the pesticide mixture composition of the kasugamycin organic acid salt and the application, the composition shows good solubility in a water solvent, floccules or precipitates are not generated, the variety of kasugamycin mixtures is effectively expanded, and the problem that a single agent is prone to generating resistance is solved.

Description

Technical Field

[0001] The invention belongs to the technical field of agriculture, and in particular relates to a kasugamycin organic acid salt pesticide mixture composition and application thereof. Background Art

[0002] Kasugamycin has been used as a pesticide antibiotic for the prevention and treatment of agricultural diseases for nearly 40 years. It is highly effective, low-toxic and environmentally friendly, so it is widely used in the prevention and treatment of various plant diseases. Kasugamycin free base is unstable in an alkaline environment, while salified kasugamycin has more beneficial effects than kasugamycin free base in terms of stability, solubility and formulation processing. Based on the production characteristics of the existing process, kasugamycin hydrochloride is the main kasugamycin salt type.

[0003] The combined use of pesticides is the main method to reduce disease resistance and maintain sustained efficacy in agriculture. The combination of kasugamycin and various fungicides has been widely studied. At present, there are nearly 100 registration certificates for kasugamycin mixtures in China, involving about 27 compounds. The main type is the combination of kasugamycin with copper preparations such as quinoline copper or copper oxychloride. However, due to the low solubility of copper preparations, the mixed form of kasugamycin and copper preparations is mainly suspension or wettable powder. The preparation requirements of suspension and wettable powder are strict, there are many types of adjuvants, the preparation process is complicated, the production cost is high, and it is also cumbersome for farmers to use.

[0004] Since the soluble preparation itself has good solubility in water, there is no need to add complex auxiliary ingredients, and the corresponding preparation process is also simpler, which greatly reduces the production cost of the enterprise and is convenient for farmers to use at the terminal. During the preparation development process, the applicant found that kasugamycin hydrochloride as the active ingredient of the soluble preparation cannot form a stable solution when used in combination with some fungicides, which greatly limits the development of kasugamycin mixtures. Summary of the invention

[0005] In view of the problems existing in the prior art, the present invention aims to provide a pesticide mixture composition, in which the kasugamycin organic acid salt is compounded with other fungicides to form a composition with good solubility. After the composition is dissolved in water, the performance is stable and no precipitation is generated.

[0006] In one aspect of the present invention, a pesticide mixture composition is provided, the composition comprises an active substance a, the active substance a is a kasugamycin organic acid salt, and the kasugamycin organic acid salt can be selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin propionate, kasugamycin malate, kasugamycin butyrate, kasugamycin tartrate, kasugamycin malonate, kasugamycin succinate, kasugamycin maleate, kasugamycin salicylate, kasugamycin benzoate and kasugamycin citrate;

[0007] Furthermore, the active substance a is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin citrate, kasugamycin malate, kasugamycin tartrate and kasugamycin propionate.

[0008] According to the composition of the present invention, the composition also contains an adjuvant acceptable to pesticides. Further, the dosage form of the composition of the present invention is selected from any one of powder, granule, ball, large granule, fine granule, microgranule, microcapsule granule, wettable powder, oil dispersible powder, water dispersible granule, emulsifiable granule, effervescent granule, dispersible tablet, effervescent tablet, sustained release agent, sustained release block, sustained release tube, sustained release granule, soluble powder, soluble granule, soluble tablet, soluble solution, water, soluble gel, oil, film spreading oil, ultra-low volume liquid, ultra-low volume microcapsule suspension, emulsifiable oil, latex, dispersible liquid, paste, concentrated gel, water emulsion, oil emulsion, microemulsion, cream, suspension, microcapsule suspension, oil suspension, suspoemulsion, seed treatment dispersible powder, seed treatment soluble powder, seed treatment liquid, seed treatment emulsion, seed treatment suspension, suspension seed coating agent, seed treatment microcapsule suspension.

[0009] Preferably, the dosage form of the composition of the present invention is selected from soluble preparations, including but not limited to soluble powders, soluble granules, soluble spheres, soluble tablets, soluble solutions, aqueous solutions, soluble gels or soluble effervescent agents.

[0010] According to the composition of the present invention, the composition further contains an active substance b, which is selected from alkyl polyamine organic acid salts or alkyl guanidine organic acid salt fungicides, and the alkyl polyamine organic acid salts or alkyl guanidine organic acid salt fungicides can be selected from one or more of docodine, octamidine acetate, and biguanide acetate; preferably, the active substance b is one or both of octamidine acetate and biguanide acetate.

[0011] According to the composition of the present invention, the mass ratio of active substance a to active substance b is 0.1:10-10:0.1; further, the mass ratio of active substance a to active substance b is 0.1:9, 0.1:8, 0.1:7, 0.1:6, 0.1:5, 0.1:4, 0.1:3, 0.1:2, 0.1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 or 9:1, any one of the values ​​or a range value between any two values. Preferably, the mass ratio of active substance a to active substance b is 0.1:1-2.5:1. Further, the mass ratio of active substance a to active substance b is 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 1.5:1, 1.8:1, 2:1, 2.1:1, 2.2:1, 2.3:1 or 2.4:1, any one of the values ​​or the range value between any two values.

[0012] Based on the total mass of the composition, the total content of the active substance a and the active substance b is 0.01-65%; further, the total content of the active substance a and the active substance b is 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55% or 60%.

[0013] Another aspect of the present invention provides use of the composition as described above in controlling plant diseases.

[0014] Another aspect of the present invention provides use of the above composition in preparing a plant disease control formulation.

[0015] Another aspect of the present invention is the use of a kasugamycin organic acid salt in the preparation of a pesticide mixture; the kasugamycin organic acid salt is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin propionate, kasugamycin malate, kasugamycin butyrate, kasugamycin tartrate, kasugamycin malonate, kasugamycin succinate, kasugamycin maleate, kasugamycin salicylate, kasugamycin benzoate and kasugamycin citrate; preferably, the kasugamycin organic acid salt is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin citrate, kasugamycin malate, kasugamycin tartrate and kasugamycin propionate.

[0016] Another aspect of the present invention is the use of kasugamycin organic acid salt as an active ingredient of a mixture in plant disease control; the kasugamycin organic acid salt is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin propionate, kasugamycin malate, kasugamycin butyrate, kasugamycin tartrate, kasugamycin malonate, kasugamycin succinate, kasugamycin maleate, kasugamycin salicylate, kasugamycin benzoate and kasugamycin citrate; preferably, the kasugamycin organic acid salt is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin citrate, kasugamycin malate, kasugamycin tartrate and kasugamycin propionate.

[0017] In another aspect of the present invention, the preparation steps of the kasugamycin salt compound include:

[0018] 1) Acidification, filtration and impurity removal of fermentation liquid;

[0019] 2) Ceramic membrane filtration;

[0020] 3) Resin adsorption and sodium hydroxide solution analysis;

[0021] 4) Acid to adjust pH;

[0022] 5) Nanofiltration to remove salt;

[0023] 6) Evaporation concentration and crystallization.

[0024] The positive improvement effect of the present invention is:

[0025] The composition of kasugamycin organic acid salt and alkyl polyamine organic acid salt or alkyl guanidine organic acid salt of the present invention exhibits good solubility, is not easy to produce floccules or precipitation, and shows a significant synergistic effect, effectively expanding the types of kasugamycin mixtures. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The figures show the dissolution conditions of mixtures of different kasugamycin salt compounds, where a is a mixture of kasugamycin hydrochloride and sinopyridamyl acetate, b is a mixture of kasugamycin oxalate and sinopyridamyl acetate, c is a mixture of kasugamycin lactate and sinopyridamyl acetate, and d is a mixture of kasugamycin acetate and sinopyridamyl acetate. DETAILED DESCRIPTION

[0027] For the purpose of the present invention, unless otherwise specified, the terms used in this application have the following meanings:

[0028] The term "formulation" refers to a stable product made from the original pesticide (mother pesticide) and suitable adjuvants, or processed by biological fermentation, plant extraction and other methods.

[0029] The term "adjuvant" refers to any single component or multiple components added to pesticide products, in addition to the active ingredient, which does not have pesticide activity and active ingredient function itself, but can or helps to enhance or improve the physical and chemical properties of the pesticide product.

[0030] The term "plant disease" refers to the phenomenon that during the growth and development of plants, due to infection by other organisms and the influence of adverse abiotic factors, the growth and development of plants is significantly hindered, and pathological changes occur in the internal and external physiology and tissue structure of the plants, resulting in morbidity or even death, resulting in reduced yield and deterioration of quality. The "plant disease" of the present application specifically refers to the disease caused by the infection of plants by other organisms, including but not limited to fungi (such as Pyricularia cinerea that can cause rice blast), or bacteria (such as Pseudomonas syringae variants that can cause bacterial angular leaf spot of cucurbits), etc.

[0031] The term "soluble preparation" refers to a clear liquid preparation whose solvent is water, or a solid preparation whose active ingredient forms a true solution in water when dissolved in water, including but not limited to soluble powders, soluble granules, soluble tablets, soluble solutions, aqueous solutions, soluble gels or soluble effervescent solutions.

[0032] The term "organic acid salt" refers to a compound prepared by the reaction of an organic acid with a free base compound, such as kasugamycin acetate prepared by the reaction of acetic acid with kasugamycin, and octamidine acetate prepared by the reaction of acetic acid with acetic acid. Depending on the difference in the number of primary or secondary amino groups in the free base compound, the free base compound can be combined with one or more organic acids. Unless otherwise specified, "organic acid salt" should include mono-organic acid salts, di-organic acid salts or tri-organic acid salts, such as octamidine acetate can include monoacetate, diacetate or triacetate.

[0033] The term "pesticide mixture" refers to a pesticide that is a mixture of two or more pesticide active ingredients.

[0034] The term "octamidine" refers to di-n-octyldiethylenetriamine, CAS 57413-95-3.

[0035] The term "dodecylguanidine" refers to dodecylguanidine acetate, CAS 2439-10-3.

[0036] The terms “around”, “about” and “substantially” refer to numerical variations within the normal experimental or measurement error range, such as “substantially” represents an error of no more than 15%, preferably no more than 10%.

[0037] The reagents and solvents used in the following examples can be purchased from commercial sources or prepared by conventional methods known to those skilled in the art. All commercially available reagents and solvents were not further purified.

[0038] 1. Preparation Example

[0039] Example 1: Preparation of Kasugamycin Hydrochloride

[0040] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0041] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0042] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0043] (4) Use hydrochloric acid to adjust the pH of the solution to about 3.0, use nanofiltration to concentrate, and then filter the solution to remove the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0044] (5) The mother liquor was evaporated and concentrated to 0.8 L at 70° C., and then cooled to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystals were collected and dried at room temperature to obtain about 63 g of kasugamycin hydrochloride.

[0045] Example 2: Preparation of Kasugamycin Oxalate

[0046] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0047] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0048] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0049] (4) Use oxalic acid to adjust the pH of the solution to about 3.5, use nanofiltration to concentrate, and then filter the solution to remove the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0050] (5) After the mother liquor was evaporated and concentrated to 0.8 L at 70° C., the temperature was lowered to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystallized product was collected and dried at room temperature to obtain about 65 g of kasugamycin oxalate.

[0051] Example 3: Preparation of Kasugamycin Lactate

[0052] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0053] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0054] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0055] (4) The pH of the obtained analytical solution was adjusted to about 4.1 using lactic acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0056] (5) The mother liquor was evaporated and concentrated to 0.8 L at 70° C., and then cooled to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystallized product was collected and dried at room temperature to obtain about 66 g of kasugamycin lactate.

[0057] Example 4: Preparation of Kasugamycin Acetate

[0058] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0059] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0060] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0061] (4) The pH of the obtained analytical solution was adjusted to about 4.0 using acetic acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0062] (5) The mother liquor was concentrated to 0.8 L by evaporation at 70° C., and then cooled to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystals were collected and dried at room temperature to obtain about 64 g of kasugamycin acetate.

[0063] Example 5: Preparation of cintamidine acetate

[0064] The acetate of fenpyroxil is prepared by reacting fenpyroxil with acetic acid. Specifically, 0.6 mol of glacial acetic acid (purity>99%) is dissolved in 1L of deionized water at room temperature to prepare an acetic acid solution, and 0.2 mol of fenpyroxil (Shenzhen Aituo Chemical Co., Ltd., purity>95%) is slowly added dropwise to the acetic acid solution at room temperature under stirring conditions. After the addition is completed, stirring is continued for 30 minutes and then vacuum evaporated to obtain a dry crystal, which is the acetate of fenpyroxil.

[0065] Example 6: Preparation of Kasugamycin Citrate

[0066] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0067] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0068] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0069] (4) The pH of the obtained analytical solution was adjusted to about 3.8 using citric acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0070] (5) The mother liquor was evaporated and concentrated to 0.8 L at 70° C., and then cooled to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystals were collected and dried at room temperature to obtain about 69 g of kasugamycin citrate.

[0071] Example 7: Preparation of Kasugamycin Malate

[0072] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0073] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0074] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0075] (4) The pH of the obtained analytical solution was adjusted to about 3.9 using malic acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0076] (5) The mother liquor was evaporated and concentrated to 0.8 L at 70° C., and then cooled to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystallized product was collected and dried at room temperature to obtain about 68 g of kasugamycin malate.

[0077] Example 8: Preparation of Kasugamycin Tartrate

[0078] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0079] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0080] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0081] (4) The pH of the obtained analytical solution was adjusted to about 3.7 using tartaric acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0082] (5) After the mother liquor was evaporated and concentrated to 0.8 L at 70° C., the temperature was lowered to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystallized product was collected and dried at room temperature to obtain about 70 g of kasugamycin tartrate.

[0083] Example 9: Preparation of Kasugamycin Propionate

[0084] (1) adjusting the pH value of 20 L of kasugamycin fermentation broth to about 3.0, filtering to remove impurities, and collecting the filtrate;

[0085] (2) filtering the filtrate with an ultrafiltration ceramic membrane, and using a styrene-divinylbenzene copolymer cross-linked structure strong acid cation exchange resin to adsorb the effective components of the obtained filtrate and remove impurities; the adsorption flow rate is 1 BV;

[0086] (3) using 0.2 mol / L sodium hydroxide solution as a decomposing agent to obtain a decomposing solution with an elution flow rate of 1 BV;

[0087] (4) The pH of the obtained analytical solution was adjusted to about 4.1 using propionic acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0088] (5) After the mother liquor was evaporated and concentrated to 0.8 L at 70° C., the temperature was lowered to 10° C. at a rate of 0.5° C. / min for cooling and crystallization. The crystallized product was collected and dried at room temperature to obtain about 65 g of kasugamycin propionate.

[0089] According to the above preparation of kasugamycin organic acid salt, other kasugamycin organic acid salts can be prepared by adjusting the type of acid agent accordingly.

[0090] 2. Effect Experiment

[0091] 1. Antibacterial test of active substances

[0092] Raw materials: kasugamycin hydrochloride (prepared in Example 1), kasugamycin oxalate (prepared in Example 2), kasugamycin lactate (prepared in Example 3) and kasugamycin acetate (prepared in Example 4); the rice blast fungus was isolated from leaves of diseased rice collected in the field.

[0093] Test method: Refer to the "Agricultural Industry Standard of the People's Republic of China NY / Tll54.7-2006", potting method. Select three-leaf rice seedlings with the same growth potential, 2 seedlings per pot, and 5 pots of test rice seedlings for each treatment. Culture the rice blast fungus on tomato oatmeal agar medium, wash the spores with sterile water after spore production, and make 1×10 5 The suspension of spores / mL was evenly sprayed on the test rice seedlings, and then covered with black plastic bags for moisturizing and cultured for 24 hours. 24 hours after inoculation, the pesticides were treated, and 5 concentration gradients were set for each pesticide. The Potter spray tower was used to spray at a pressure of 50Psi, and about 5mL was used for each pot. After spraying, the rice seedlings were placed at about 26℃ and relative humidity>90% for culture. After 7 days, the disease index of the whole leaf was investigated according to the grading standard of rice blast, and the control effect was calculated.

[0094] Disease index = {[∑(number of diseased leaves at each level of each treatment × corresponding level value)] / total number of leaves investigated × 9} × 100;

[0095] The control effect (%) = [(blank control disease index - drug treatment disease index) / blank control disease index] × 100.

[0096] The control effect was converted into a probability value (y), the concentration of the drug solution (ug / ml) was converted into a logarithmic value (x), and the inhibition concentration EC50 was calculated. The results are shown in Table 1.

[0097] Table 1 Antibacterial effects of different kasugamycin salt compounds

[0098]

[0099] The bactericidal active substance of kasugamycin salt compounds is kasugamycin free base, so the antibacterial effects of different kasugamycin salt compounds are basically equivalent, with EC50 ranging from about 24 to 29 μg / mL, showing excellent antibacterial effects.

[0100] 2. Solubility test of different mixtures

[0101] 2 g of kasugamycin hydrochloride (prepared in Example 1), 2 g of kasugamycin oxalate (prepared in Example 2), 2 g of kasugamycin lactate (prepared in Example 3) and 2 g of kasugamycin acetate (prepared in Example 4) were dissolved in 98 mL of deionized water in a beaker to prepare different types of kasugamycin salt aqueous solutions with a mass fraction of 2%.

[0102] 1 g of cintamidine acetate was slowly added to different types of kasugamycin salt aqueous solutions under stirring at room temperature. Stirring was stopped after the addition of cintamidine acetate. The solution was poured into a test tube for observation. After standing for 1 min and 30 min, the liquid in the test tube was irradiated with a fluorescent lamp. The clarification and precipitation were determined by naked eyes. The experimental results are shown in Table 2 and Table 3. Figure 1 shown.

[0103] Table 2 Dissolution of different kasugamycin salt compounds and cintamidine acetate

[0104]

[0105] Through Table 2 and Figure 1 It can be seen that the solution after kasugamycin hydrochloride and sinocamptobacyl acetate were compounded, and a large amount of flocculent insoluble matter appeared after standing for 1 minute, and there was obvious precipitation at the bottom of the test tube after standing for 30 minutes, indicating that kasugamycin hydrochloride is not suitable for compounding with sinocamptobacyl acetate to prepare a pesticide mixture. Similarly, the solution after kasugamycin oxalate and sinocamptobacyl acetate were compounded also had some flocculent insoluble matter after standing for 1 minute, and there was some precipitation at the bottom after 30 minutes, which was also not suitable as a pesticide mixture. Although the solution of kasugamycin lactate and kasugamycin acetate compounded with sinocamptobacyl acetate was brown in color, the solution formed had good clarity and no obvious precipitation, which was suitable for spraying and storage, and could be used as a pesticide mixture. The above experimental results show that not all types of kasugamycin organic acid salts are suitable for preparing pesticide mixtures, which needs to be verified by compounding solubility experiments.

[0106] Using the same solubility test method, kasugamycin citrate (prepared in Example 6), kasugamycin malate (prepared in Example 7), kasugamycin tartrate (prepared in Example 8), kasugamycin propionate (prepared in Example 9) were compounded with octhilinone acetate, and their solubility was detected. It was found that the solutions after compounding kasugamycin citrate and kasugamycin malate were also good clear solutions, while the solutions after compounding kasugamycin tartrate and kasugamycin propionate were basically clear, with a little foggy insoluble matter in the solutions. The above four organic acid salts of kasugamycin can all be prepared into pesticide mixtures for use.

[0107] In order to further verify the effect after compounding a specific type of kasugamycin organic acid salt, we selected kasugamycin lactate for a co-toxicity experiment.

[0108] 3. Co-toxicity experiment of kasugamycin lactate and octhilinone acetate

[0109] Raw materials: kasugamycin lactate (prepared by the method of Example 3), octhilinone acetate (prepared by the method of Example 5); Magnaporthe oryzae was isolated from the leaves of diseased rice plants in the field.

[0110] Method: According to the relevant method in "Section 1 Antibacterial Experiment of Active Substances", the EC50 values of octhilinone acetate and kasugamycin lactate·octhilinone acetate mixtures at different mass ratios were measured, and the toxicity index and co-toxicity coefficient (CTC) of the agents were calculated according to the Sun Yunpei method.

[0111] Toxicity index of single agent = standard agent EC50 / test single agent EC50 × 100;

[0112] Actual measured toxicity index (ATI) = (standard agent EC50 / test agent EC50) × 100;

[0113] Theoretical toxicity index of mixture (TTI) = toxicity index of agent A × percentage content of A in the mixture + toxicity index of agent B × percentage content of B in the mixture;

[0114] Co-toxicity coefficient (CTC) = [actual measured toxicity index of mixture (ATI) / theoretical toxicity index of mixture (TTI)] × 100;

[0115] When CTC ≤ 80, the composition shows antagonistic effect. When 80 < CTC < 120, the composition shows additive effect. When CTC ≥ 120, the composition shows synergistic effect.

[0116] Table 3 Co-toxicity experiment data

[0117]

[0118]

[0119] Note: "Chun" refers to kasugamycin lactate, and "Xin" refers to cinamide acetate

[0120] It can be seen from Table 3 that the mixture of kasugamycin lactate and cintamidine acetate has an additive control effect in the mass ratio range of 5:1-10:1. The solution of the mixture after dissolving in water within this ratio range can remain clear, which is conducive to the application of the mixture in the terminal and thus avoids problems such as resistance to a single agent. At the same time, the mixture has an unexpected synergistic effect in the mass ratio range of 0.1:1-2.5:1.

[0121] Example 10: Preparation of Kasugamycin Lactate and Sintramycin Acetate Aqueous Solution

[0122] The following components are available:

[0123] Kasugamycin lactate (prepared in Example 3) 2 g;

[0124] 1 g of octamidine acetate (prepared in Example 5);

[0125] Tween 80 0.5g;

[0126] AEO-9 0.2g;

[0127] Deionized water 96.3 g;

[0128] First, cincomycin acetate is dissolved in 50 mL of deionized water to form a cincomycin acetate solution; kasugamycin lactate, Tween 80 and AEO-9 are sequentially added into the remaining deionized water, stirred and dissolved to form a kasugamycin lactate solution, and then the cincomycin acetate solution is slowly added into the kasugamycin lactate solution under stirring conditions to prepare a 3% kasugamycin lactate·cincomycin acetate aqueous solution.

[0129] Referring to the test requirements of "GB / T34774-2017 Kasugamycin Aqueous Solution", the water-insoluble matter, dilution stability, low-temperature stability and thermal storage stability of Kasugamycin lactate·sinopyram acetate aqueous solution were tested. The results are shown in Table 4. The indicators of relevant control items all meet the requirements.

[0130] Table 4 Test results of Kasugamycin lactate·Sintramycin acetate aqueous solution

[0131] project index Water insoluble matter %≤ 0.5 Dilution stability (20 times dilution) qualified Low temperature stability qualified High temperature stability qualified

[0132] Example 11: Kasugamycin lactate·dodecine soluble powder

[0133] Weigh 30g of kasugamycin lactate (prepared in Example 3), 10g of dodine (purchased from Rudong County Huasheng Chemical Co., Ltd.), 10g of Sokalan HP, 20g of sodium lauryl sulfate, and 930g of sodium sulfate. Mix the above raw materials and prepare 4% kasugamycin lactate dodine soluble powder after air flow milling.

[0134] Take 10g of the above soluble powder and add it to 50ml of deionized water. After stirring for about 10s and standing for 5min, observe that the solution is basically clear without obvious precipitation.

[0135] Example 12: Kasugamycin acetate·dodecine soluble powder

[0136] The preparation method of 4% kasugamycin acetate·dolin soluble powder is basically the same as that of Example 11, except that kasugamycin lactate is replaced by kasugamycin acetate.

[0137] Take 10g of the above soluble powder and add it to 50ml of deionized water. After stirring for about 10s and standing for 5min, observe that the solution is clear without obvious precipitation.

[0138] Comparative Example 1: Kasugamycin hydrochloride·Dodine soluble powder

[0139] The preparation method of 4% kasugamycin hydrochloride·dolin soluble powder is basically the same as that of Example 11, except that kasugamycin lactate is replaced by kasugamycin hydrochloride.

[0140] Take 10g of the above-mentioned kasugamycin hydrochloride·dodecine soluble powder and add it to 50ml of deionized water. After stirring for about 10s and letting it stand for 5min, it can be clearly observed that there are suspended matter in the solution and obvious sediment at the bottom of the solution. It is not suitable for use as a pesticide mixture.

[0141] Example 13: Kasugamycin lactate·biguanide acetate soluble powder

[0142] Weigh 30g of kasugamycin lactate (prepared in Example 3), 20g of octyl guanidine acetate (purchased from Hubei Baidu Chemical Co., Ltd.), 15g of Sokalan HP, 20g of sodium lauryl sulfate, and 915g of sodium sulfate. Mix the above raw materials and prepare 5% kasugamycin lactate octyl guanidine acetate soluble powder after air flow milling.

[0143] Take 10g of the above soluble powder and add it to 50ml of deionized water. After stirring for about 10s and standing for 5min, observe that the solution is clear without obvious precipitation.

[0144] Comparative Example 2: Kasugamycin hydrochloride·biguanide acetate soluble powder

[0145] The preparation method of 5% kasugamycin hydrochloride·biguanide acetate soluble powder is basically the same as that of Example 13, except that kasugamycin lactate is replaced by kasugamycin hydrochloride.

[0146] 10 g of the above 5% kasugamycin hydrochloride·biguanide acetate soluble powder was added to 50 ml of deionized water, stirred for about 10 seconds and allowed to stand for 5 minutes, and obvious flocs were observed in the solution and some sediments were found at the bottom.

[0147] Example 14: Kasugamycin citrate·thiophanate-methyl water dispersible granules

[0148] Weigh 40g of kasugamycin citrate (prepared in Example 6), 10g of thiophanate-methyl (purchased from Shaanxi Xida Huate Technology Industry Co., Ltd.), 20g of sodium dodecylbenzene sulfonate, 55g of starch, 5g of polyethylene glycol and 870g of sodium glauber salt, mix the above components according to the weight of the formula, grind them with an ultrafine grinder, add a certain amount of water and mix them, then extrude them into a material, and after drying and sieving, obtain 5% kasugamycin citrate·thiophanate-methyl water dispersible granules.

[0149] Take 10g of the above water-dispersible particles and add them to 50ml of deionized water. After stirring for about 10s and letting it stand for 5min, it is observed to be a basically clear solution with no obvious precipitation.

[0150] Example 15: Kasugamycin lactate·thiophanate-methyl water dispersible granules

[0151] The preparation method of 5% kasugamycin lactate·thiophanate-methyl water dispersible granules is basically the same as that of Example 14, except that kasugamycin citrate is replaced by kasugamycin lactate.

[0152] Take 10g of the above water-dispersible particles and add them to 50ml of deionized water. After stirring for about 10s and letting it stand for 5min, observe that it is a clear solution with no obvious precipitation.

[0153] Example 16: Kasugamycin propionate·Cyclobutanil solution

[0154] Weigh 20 g of kasugamycin propionate (prepared in Example 9), 50 g of propamocarb (purchased from Jiangsu Lanfeng Biochemical Co., Ltd.), 10 g of TX-10, 20 g of AEO-9, 30 g of urea, and 870 g of deionized water, add the above components to the deionized water in sequence, stir evenly, and obtain a clear, precipitate-free 7% kasugamycin propionate·propamocarb soluble solution.

[0155] Example 17: Kasugamycin acetate·Cyclobutanil solution

[0156] The preparation method of 7% kasugamycin acetate·promocarb soluble solution is basically the same as that of Example 16, except that kasugamycin propionate is replaced by kasugamycin acetate. The soluble solution is clear and has no precipitation.

[0157] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

[0158] Finally, it should be noted that the terms "comprises," "includes," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements that are inherent to such process, method, article, or apparatus.

Claims

1. A pesticide mixture composition, characterized in that: The composition contains an active substance a and an adjuvant acceptable to pesticides, wherein the active substance a is an organic acid salt of kasugamycin, and the organic acid salt of kasugamycin is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin propionate, kasugamycin malate, kasugamycin butyrate, kasugamycin tartrate, kasugamycin malonate, kasugamycin succinate, kasugamycin maleate, kasugamycin salicylate, kasugamycin benzoate and kasugamycin citrate.

2. The composition according to claim 1, characterized in that The active substance a is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin citrate, kasugamycin malate, kasugamycin tartrate and kasugamycin propionate.

3. The composition according to claim 1 or 2, characterized in that The dosage form of the composition is any one of powder, granule, ball, large granule, fine granule, microgranule, microcapsule granule, wettable powder, oil-dispersible powder, water-dispersible granule, emulsifiable granule, effervescent granule, dispersible tablet, effervescent tablet, sustained-release agent, sustained-release block, sustained-release tube, sustained-release granule, soluble powder, soluble granule, soluble tablet, soluble solution, water, soluble gel, oil, film-spreading oil, ultra-low volume liquid, ultra-low volume microcapsule suspension, emulsifiable oil, latex, dispersible liquid, paste, concentrated gel, water emulsion, oil emulsion, microemulsion, ointment, suspension, microcapsule suspension, oil suspension, suspoemulsion, seed treatment dispersible powder, seed treatment soluble powder, seed treatment liquid, seed treatment emulsion, seed treatment suspension, suspended seed coating agent and seed treatment microcapsule suspension.

4. The composition according to claim 1 or 2, characterized in that The dosage form of the composition is a soluble preparation.

5. The composition according to any one of claims 1 to 4, characterized in that The composition further contains an active substance b, which is an alkyl polyamine organic acid salt and / or an alkyl guanidine organic acid salt fungicide.

6. The composition according to claim 5, characterized in that The active substance b is selected from one or more of docodine, octamidine acetate and octamidine acetate; preferably one or two of octamidine acetate and octamidine acetate.

7. The composition according to any one of claims 5 or 6, characterized in that The mass ratio of the active substance a to the active substance b is 0.1:10-10:0.1, preferably 0.1:1-2.5:

1.

8. The composition according to any one of claims 5 to 7, wherein the total content of the active substance a and the active substance b is 0.01-65% based on the total mass of the pesticide composition.

9. Use of the composition according to any one of claims 1 to 8 in controlling plant diseases.

10. Use of the composition according to any one of claims 1 to 8 in the preparation of a plant disease control formulation.

11. The use of kasugamycin organic acid salt in the preparation of pesticide mixtures, characterized in that: The kasugamycin organic acid salt is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin propionate, kasugamycin malate, kasugamycin butyrate, kasugamycin tartrate, kasugamycin malonate, kasugamycin succinate, kasugamycin maleate, kasugamycin salicylate, kasugamycin benzoate and kasugamycin citrate.

12. Use of kasugamycin organic acid salt as an active ingredient of pesticide mixture in plant disease control, characterized in that: The kasugamycin organic acid salt is selected from one or more of kasugamycin acetate, kasugamycin lactate, kasugamycin propionate, kasugamycin malate, kasugamycin butyrate, kasugamycin tartrate, kasugamycin malonate, kasugamycin succinate, kasugamycin maleate, kasugamycin salicylate, kasugamycin benzoate and kasugamycin citrate.

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