PESTICIDE PREPARATIONS AND PESTICIDE COMPOSITIONS

Abstract

The invention relates to organic acid salts of kasugamyxin, compound insecticide preparations containing these salts and their applications, preparations exhibiting good solubility in aqueous solvents, not forming flocs or precipitates, effectively expanding the range of compound active ingredients of kasugamyxin, and overcoming the disadvantage of easily developing resistance when using single preparations.

Description

Kasugamycin organic acid salt, pesticide composition containing same and application thereof

[0001] Priority information

[0002] The present invention claims priority to and benefits of patent application CN202311336790.6 filed with the State Intellectual Property Office of China on October 16, 2023 and patent application CN202311339532.3 filed with the State Intellectual Property Office of China on October 16, 2023, and incorporates the entirety of each of them herein by reference. Technical Field

[0003] The invention belongs to the technical field of agriculture, and in particular relates to kasugamycin organic acid salt, a pesticide composition containing the same and application thereof. Background Art

[0004] Kasugamycin, a pesticide antibiotic, has been used for nearly 40 years to control agricultural diseases. Its high efficacy, low toxicity, and environmental friendliness have led to its widespread use in the prevention and treatment of various plant diseases. Kasugamycin free base is unstable in alkaline environments, while salted kasugamycin exhibits more beneficial effects than free base in terms of stability, solubility, and formulation processing. Based on the production characteristics of existing processes, kasugamycin hydrochloride is the predominant kasugamycin salt form.

[0005] Combining pesticides is a primary method for reducing disease resistance and maintaining sustained efficacy in agriculture. The combination of kasugamycin with various fungicides has been extensively studied. Currently, there are nearly 100 registered kasugamycin mixtures in China, involving approximately 27 compounds. The main type is kasugamycin combined with copper preparations such as quinoline copper or copper oxychloride. However, due to the low solubility of copper preparations, kasugamycin-copper mixtures are primarily formulated as suspension concentrates or wettable powders. These suspension concentrates and wettable powders have stringent formulation requirements, require a wide variety of adjuvants, have complex preparation processes, and have high production costs. Furthermore, they are relatively cumbersome for farmers to use.

[0006] Because the soluble formulation itself has good solubility in water, it does not require the addition of complex auxiliary ingredients. The corresponding preparation process is also simpler, greatly reducing the production costs of enterprises and facilitating end-use by farmers. During the formulation development process, the applicant discovered that kasugamycin hydrochloride, as the active ingredient of the soluble formulation, could not form a stable solution when combined with some fungicides, which greatly limited the development of kasugamycin mixtures.

[0007] Summary of the Invention

[0008] In response to the problems existing in the prior art, the present invention aims to provide a pesticide composition, in which the organic acid salt of kasugamycin 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.

[0009] In one aspect of the present invention, a pesticide composition is provided, which comprises an active substance a and an active substance b, wherein the active substance a is an organic acid salt of kasugamycin, and the active substance b is selected from an alkyl polyamine organic acid salt or an alkyl guanidine organic acid salt fungicide.

[0010] Furthermore, the active substance a can be specifically 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;

[0011] Furthermore, the active substance b can be specifically selected from one or more of dodine, octamidine acetate, and octamidine acetate.

[0012] 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; and the active substance b is one or both of octamidine acetate and octamidine acetate.

[0013] 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 between any two values.

[0014] According to the composition of the present invention, further, 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 value or a range value between any two values.

[0015] Furthermore, the composition is a formulation containing an adjuvant that is acceptable for pesticides. Still further, the formulation of the present invention is in the form of a powder, granules, pellets, granules, fine granules, microgranules, microcapsule granules, wettable powders, oil-dispersible powders, water-dispersible granules, emulsifiable granules, effervescent granules, dispersible tablets, effervescent tablets, sustained-release agents, sustained-release blocks, sustained-release tubes, sustained-release granules, soluble powders, soluble granules, soluble tablets, soluble solutions, aqueous solutions, soluble gels, oils, film-spreading oils, ultra-low volume liquids, ultra-low volume microcapsule suspensions, emulsifiable concentrates, latexes, dispersible liquids, pastes, concentrated gels, aqueous emulsions, oil emulsions, microemulsions, ointments, suspensions, microcapsule suspensions, oil suspensions, suspoemulsions, dispersible powders for seed treatment, soluble powders for seed treatment, liquid solutions for seed treatment, emulsions for seed treatment, suspensions for seed treatment, and microcapsule suspensions for seed treatment.

[0016] Preferably, the dosage form of the preparation of the present invention is selected from soluble preparations, including but not limited to soluble powders, soluble granules, soluble tablets, soluble solutions, aqueous solutions, soluble gels or soluble effervescent solutions.

[0017] Based on the total mass of the preparation, 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%.

[0018] In one aspect of the present invention, a pesticide mixture composition is provided, which contains an active substance a, wherein 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.

[0019] 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.

[0020] The composition according to the present invention further comprises an agriculturally acceptable adjuvant.

[0021] Furthermore, the dosage form of the composition of the present invention is selected from any one of powders, granules, balls, large granules, fine granules, microgranules, microcapsule granules, wettable powders, oil-dispersible powders, water-dispersible granules, emulsifiable granules, effervescent granules, dispersible tablets, effervescent tablets, sustained-release agents, sustained-release blocks, sustained-release tubes, sustained-release particles, soluble powders, soluble granules, soluble tablets, soluble solutions, aqueous solutions, soluble gels, oils, film-spreading oils, ultra-low volume liquids, ultra-low volume microcapsule suspensions, emulsifiable concentrates, latexes, dispersible liquids, pastes, concentrated gels, emulsions in water, oil emulsions, microemulsions, ointments, suspensions, microcapsule suspensions, oil suspensions, suspoemulsions, dispersible powders for seed treatment, soluble powders for seed treatment, seed treatment liquids, seed treatment emulsions, seed treatment suspensions, suspended seed coatings, and microcapsule suspensions for seed treatment.

[0022] 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 effervescents.

[0023] 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 dococlomid, octamidine acetate, and octamidine acetate; preferably, the active substance b is one or both of octamidine acetate and octamidine acetate.

[0024] 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 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, or a range value between any two values.

[0025] 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%.

[0026] Another aspect of the present invention provides use of any of the above compositions in controlling plant diseases.

[0027] Another aspect of the present invention provides use of any of the above compositions in preparing a plant disease control formulation.

[0028] 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.

[0029] Another aspect of the present invention is the use of a kasugamycin organic acid salt as an active ingredient in a mixture for 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.

[0030] In another aspect of the present invention, the preparation steps of the kasugamycin salt compound include:

[0031] 1) Acidification of fermentation broth, filtration and impurity removal;

[0032] 2) Ceramic membrane filtration;

[0033] 3) Resin adsorption and sodium hydroxide solution analysis;

[0034] 4) Acid to adjust pH;

[0035] 5) Nanofiltration desalination;

[0036] 6) Evaporation concentration and crystallization.

[0037] The positive improvement effect of the present invention is:

[0038] The composition of the kasugamycin organic acid salt and the alkyl polyamine organic acid salt or the alkyl guanidine organic acid salt of the present invention exhibits good solubility, is not prone to generating flocs or precipitation, and shows a significant synergistic effect, effectively expanding the types of kasugamycin mixtures. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 shows the dissolution 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

[0040] For the purpose of the present invention, unless otherwise specified, the terms used in this application have the following meanings:

[0041] The term "formulation" refers to a stable product made from pesticide technical (mother drug) and suitable adjuvants, or processed by methods such as biological fermentation and plant extraction.

[0042] 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 or active ingredient function itself, but can or helps to enhance or improve the physical and chemical properties of the pesticide product.

[0043] The term "plant disease" refers to a phenomenon in which a plant's growth and development is significantly hindered by infection from other organisms and adverse abiotic factors during its growth and development. Pathological changes occur in the plant's internal and external physiology and tissue structure, leading to morbidity or even death, resulting in reduced yield and poor quality. The term "plant disease" as used herein specifically refers to diseases caused by infection by other organisms, including but not limited to fungi (e.g., Pyricularia cinerea, which causes rice blast) or bacteria (e.g., Pseudomonas syringae variants, which causes bacterial angular leaf spot in cucurbits).

[0044] 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.

[0045] 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 octamidine with acetic acid. Depending on the number of primary or secondary amino groups in the free base compound, the free base compound may be combined with one or more organic acids. Unless otherwise specified, "organic acid salt" includes mono-, di-, or tri-organic acid salts, such as octamidine acetate, which includes monoacetate, diacetate, or triacetate.

[0046] The term "pesticide mixture" refers to a pesticide that is a mixture of two or more pesticide active ingredients.

[0047] The term "octamidine" refers to di-n-octyldiethylenetriamine, CAS 57413-95-3.

[0048] The term "dodine" refers to dodecylguanidine acetate, CAS 2439-10-3.

[0049] 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%.

[0050] 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.

[0051] 1. Preparation Example

[0052] Example 1: Preparation of Kasugamycin Hydrochloride

[0053] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0054] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0055] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0056] (4) Use hydrochloric acid to adjust the pH of the solution to about 3.0, use nanofiltration to concentrate, and then filter the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0057] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 63 g of kasugamycin hydrochloride.

[0058] Example 2: Preparation of Kasugamycin Oxalate

[0059] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0060] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0061] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0062] (4) Use oxalic acid as an acid to adjust the pH of the solution to about 3.5, use nanofiltration to concentrate, and then filter the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0063] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 65 g of kasugamycin oxalate.

[0064] Example 3: Preparation of Kasugamycin Lactate

[0065] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0066] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0067] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0068] (4) The pH of the obtained solution was adjusted to about 4.1 using lactic acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0069] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 66 g of kasugamycin lactate.

[0070] Example 4: Preparation of Kasugamycin Acetate

[0071] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0072] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0073] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0074] (4) Use acetic acid as an acid to adjust the pH of the obtained solution to about 4.0, and use nanofiltration to concentrate and circulate the filtration to remove the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0075] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 64 g of kasugamycin acetate.

[0076] Example 5: Preparation of cintamidine acetate

[0077] Sinafop acetate is prepared by reacting sinafop with acetic acid. Specifically, 0.6 mol of glacial acetic acid (purity >99%) is dissolved in 1 L of deionized water at room temperature to prepare an acetic acid solution. 0.2 mol of sinafop (Shenzhen Aituo Chemical Co., Ltd., purity >95%) is slowly added dropwise to the acetic acid solution at room temperature with stirring. After the addition is complete, stirring is continued for 30 minutes before vacuum evaporation. The resulting dry crystals are sinafop acetate.

[0078] Example 6: Preparation of Kasugamycin Citrate

[0079] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0080] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0081] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0082] (4) The pH of the obtained solution was adjusted to about 3.8 using citric acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0083] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 69 g of kasugamycin citrate.

[0084] Example 7: Preparation of Kasugamycin Malate

[0085] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0086] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0087] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0088] (4) The pH of the obtained solution was adjusted to about 3.9 using malic acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0089] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 68 g of kasugamycin malate.

[0090] Example 8: Preparation of Kasugamycin Tartrate

[0091] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0092] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0093] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0094] (4) The pH of the obtained solution was adjusted to about 3.7 using tartaric acid, and the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0095] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 70 g of kasugamycin tartrate.

[0096] Example 9: Preparation of Kasugamycin Propionate

[0097] (1) The pH value of 20 L of kasugamycin fermentation broth was adjusted to about 3.0, impurities were removed by filtration, and the filtrate was collected;

[0098] (2) The filtrate is filtered using an ultrafiltration ceramic membrane, and the obtained filtrate is adsorbed with a styrene-divinylbenzene copolymer cross-linked structure strong acidic cation exchange resin to remove impurities; the adsorption flow rate is 1 BV;

[0099] (3) 0.2 mol / L sodium hydroxide solution was used as an analytical agent to obtain an analytical solution with an elution flow rate of 1 BV;

[0100] (4) Use propionic acid as an acid to adjust the pH of the obtained solution to about 4.1, and use nanofiltration to concentrate and circulate the filtration to remove the remaining Na + Salt; repeated nanofiltration to obtain about 5L of mother liquor;

[0101] (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 crystallization. The crystalline product was collected and dried at room temperature to obtain about 65 g of kasugamycin propionate.

[0102] 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.

[0103] 2. Effect Experiment

[0104] 1. Antibacterial test of active substances

[0105] 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.

[0106] Test method: Refer to the "Agricultural Industry Standard of the People's Republic of China NY / T1154.7-2006" and use the potting method. Three-leaf rice seedlings with consistent growth were selected, with two seedlings per pot. Five pots of test rice seedlings were used for each treatment. The rice blast fungus was cultured on tomato oatmeal agar medium. After spore production, the spores were washed with sterile water and prepared into 1×10 5 A suspension containing 100 spores / mL was evenly sprayed onto the test rice seedlings. After inoculation, the seedlings were covered with a black plastic bag to maintain moisture and incubate for 24 hours. Twenty-four hours after inoculation, the seedlings were treated with the following pesticides: five concentration gradients of each pesticide were applied using a Potter spray tower at 50 psi, with approximately 5 mL applied to each pot. Following spraying, the seedlings were incubated at approximately 26°C and a relative humidity >90%. Seven days later, the disease index of the entire leaf was assessed according to the Rice Blast Disease Grading Standard, and the control efficacy was calculated.

[0107] Disease index = {[∑(number of diseased leaves at each level of each treatment × corresponding level value)] / total number of leaves surveyed × 9} × 100;

[0108] Control effect (%) = [(blank control disease index - drug treatment disease index) / blank control disease index] × 100.

[0109] 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.

[0110] Table 1 Antibacterial effects of different kasugamycin salt compounds

[0111] The bactericidal active substance of the kasugamycin salt-type compound is kasugamycin free base, so the antibacterial effects of different kasugamycin salt-type compounds are basically equivalent, with EC50 ranging from approximately 24 to 29 μg / mL, showing excellent antibacterial effects.

[0112] 2. Solubility test of different mixtures

[0113] 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%.

[0114] At room temperature, 1 g of cinclopyralid acetate was slowly added to different types of kasugamycin salt aqueous solutions under stirring. Stirring was stopped after the addition of cinclopyralid acetate. The solution was poured into a test tube for easy observation. After standing for 1 minute and 30 minutes, the liquid in the test tube was irradiated with a fluorescent lamp, and the clarification and precipitation were determined by the naked eye. The experimental results are shown in Table 2 and Figure 1.

[0115] Table 2 Dissolution of different kasugamycin salt compounds and cintamidine acetate

[0116] As shown in Table 2 and Figure 1, the solution after kasugamycin hydrochloride and cintamidine acetate were compounded, a large amount of flocculent insoluble matter appeared after standing for 1 minute, and there was obvious sediment at the bottom of the test tube after standing for 30 minutes, indicating that kasugamycin hydrochloride is not suitable for compounding with cintamidine acetate to prepare a pesticide mixture. Similarly, the solution after kasugamycin oxalate and cintamidine acetate were compounded also had some flocculent insoluble matter after standing for 1 minute, and some sediment at the bottom after 30 minutes, which is also not suitable as a pesticide mixture. However, the solution after kasugamycin lactate and kasugamycin acetate were compounded with cintamidine acetate, although brown in color, had good clarity and no obvious sediment, making it suitable for spraying and storage and can be used as a pesticide mixture. The above experimental results show that not all types of kasugamycin organic acid salts are suitable for preparation as pesticide mixtures, which needs to be verified by compounding solubility experiments.

[0117] Using the same solubility experimental method, kasugamycin citrate (prepared in Example 6), kasugamycin malate (prepared in Example 7), kasugamycin tartrate (prepared in Example 8), and kasugamycin propionate (prepared in Example 9) were compounded with cintamidine acetate to test their solubility. The results showed that the solution after kasugamycin citrate and kasugamycin malate were compounded also showed a good clear solution, while the solution after kasugamycin tartrate and kasugamycin propionate were basically clear, with a small amount of mist-like insoluble matter in the solution. The above four kasugamycin organic acid salts can all be prepared into pesticide mixtures for use.

[0118] In order to further verify the effect of compounding specific organic acid salts of kasugamycin, we selected kasugamycin lactate for co-toxicity experiments.

[0119] 3. Co-toxicity experiment of kasugamycin lactate and cinclostrobin acetate

[0120] Raw materials: kasugamycin lactate (prepared according to the method of Example 3), cinclostrobin acetate (prepared according to the method of Example 5); rice blast fungus was isolated from leaves of diseased rice in the field.

[0121] Method: According to the relevant method in "Antibacterial Experiment of Active Substances in Section 1", the EC50 values of validamycin lactate and validamycin lactate·acetic acid of jinggangmycin at different mass ratios were determined, and the virulence index and co-toxicity coefficient (CTC) of the agents were calculated according to the Sun Yunpei method.

[0122] Virulence index of single agent = Standard agent EC50 / Tested single agent EC50 × 100;

[0123] Actual virulence index (ATI) = (Standard agent EC50 / Tested agent EC50) × 100;

[0124] Theoretical virulence index (TTI) of mixture = Virulence index of agent A × Percentage content of A in mixture + Virulence index of agent B × Percentage content of B in mixture;

[0125] Co-toxicity coefficient (CTC) = [Actual virulence index (ATI) of mixture / Theoretical virulence index (TTI) of mixture] × 100;

[0126] 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.

[0127] Table 3 Co-toxicity experiment data

[0128] Note: "Chun" refers to validamycin lactate, and "Xin" refers to acetic acid of jinggangmycin

[0129] As can be seen from Table 3, the mixture of validamycin lactate·acetic acid of jinggangmycin has an additive control effect in the mass ratio range of 5:1 - 10:1. The solution of the mixture after dissolving in water can remain clear in this ratio range, which is beneficial to the application of the mixture at the terminal and can avoid problems such as resistance caused by single agents. At the same time, the mixture has an unexpected synergistic effect in the mass ratio range of 0.1:1 - 2.5:1.

[0130] Example 10: Preparation of validamycin lactate·acetic acid of jinggangmycin aqueous solution

[0131] The following components are provided:

[0132] Validamycin lactate (prepared in Example 3) 2 g;

[0133] Acetic acid of jinggangmycin (prepared in Example 5) 1 g;

[0134] Tween 80 0.5 g;

[0135] AEO-9 0.2 g;

[0136] Deionized water 96.3 g;

[0137] First, octamidine acetate is dissolved in 50 mL of deionized water to form an octamidine acetate solution; kasugamycin lactate, Tween 80 and AEO-9 are sequentially added to the remaining deionized water and stirred to dissolve to form a kasugamycin lactate solution; then, the octamidine acetate solution is slowly added to the kasugamycin lactate solution under stirring to prepare a 3% kasugamycin lactate-octamidine acetate aqueous solution.

[0138] The water-insoluble matter, dilution stability, low-temperature stability, and heat storage stability of kasugamycin lactate·octamidine acetate aqueous solution were tested with reference to the test requirements of "GB / T34774-2017 Kasugamycin Aqueous Solution". The results are shown in Table 4. The relevant control item indicators all met the requirements.

[0139] Table 4 Test results of Kasugamycin lactate·Cinnamyl acetate aqueous solution

[0140] Example 11: Kasugamycin lactate·dodine soluble powder

[0141] 30 g of kasugamycin lactate (prepared in Example 3), 10 g of dodine (purchased from Rudong County Huasheng Chemical Co., Ltd.), 10 g of Sokalan HP, 20 g of sodium lauryl sulfate, and 930 g of sodium sulfate were weighed and mixed, and then jet milled to produce a 4% kasugamycin lactate dodine soluble powder.

[0142] Take 10g of the above soluble powder and add it to 50ml of deionized water. After stirring for about 10s and letting it stand for 5min, observe that the solution is basically clear with no obvious precipitation.

[0143] Example 12: Kasugamycin acetate·dodine soluble powder

[0144] 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.

[0145] Take 10g of the above soluble powder and add it to 50ml of deionized water. After stirring for about 10s and letting it stand for 5min, observe that the solution is clear without obvious precipitation.

[0146] Comparative Example 1: Kasugamycin hydrochloride and doxorubicin soluble powder

[0147] The preparation method of 4% kasugamycin hydrochloride·dodine soluble powder is basically the same as that of Example 11, except that kasugamycin lactate is replaced by kasugamycin hydrochloride.

[0148] Take 10g of the above-mentioned kasugamycin hydrochloride and doxorubicin 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.

[0149] Example 13: Kasugamycin lactate-octylguanidine acetate soluble powder

[0150] 30 g of kasugamycin lactate (prepared in Example 3), 20 g of octylamine acetate (purchased from Hubei Baidu Chemical Co., Ltd.), 15 g of Sokalan HP, 20 g of sodium lauryl sulfate, and 915 g of sodium sulfate were weighed and mixed, and then jet milled to produce a 5% kasugamycin lactate-octylamine acetate soluble powder.

[0151] Take 10g of the above soluble powder and add it to 50ml of deionized water. After stirring for about 10s and letting it stand for 5min, observe that the solution is clear without obvious precipitation.

[0152] Comparative Example 2: Kasugamycin hydrochloride and octylguanidine acetate soluble powder

[0153] The preparation method of 5% kasugamycin hydrochloride·octanolamine acetate soluble powder is basically the same as that of Example 13, except that kasugamycin lactate is replaced by kasugamycin hydrochloride.

[0154] 10 g of the above 5% kasugamycin hydrochloride·octanolamine acetate soluble powder was added to 50 ml of deionized water, stirred for about 10 seconds and allowed to stand for 5 minutes. Obvious flocs were observed in the solution and some sediment was found at the bottom.

[0155] Example 14: Kasugamycin citrate·thiophanate-methyl water dispersible granules

[0156] Weigh 40 g of kasugamycin citrate (prepared in Example 6), 10 g of thiamethoxam (purchased from Shaanxi Xida Huate Technology Industry Co., Ltd.), 20 g of sodium dodecylbenzenesulfonate, 55 g of starch, 5 g of polyethylene glycol and 870 g of sodium sulfate, and fully mix the above components according to the weight of the formula. Grind them with an ultrafine grinder, add a certain amount of water, mix them, and then extrude them into a material. After drying and sieving, 5% kasugamycin citrate·thiamethoxam water-dispersible granules are obtained.

[0157] 10 g of the above water-dispersible particles were added to 50 ml of deionized water, stirred for about 10 seconds, and allowed to stand for 5 minutes. The solution was observed to be basically clear with no obvious precipitation.

[0158] Example 15: Kasugamycin lactate·thiamethoxam water dispersible granules

[0159] The preparation method of 5% kasugamycin lactate·thiophanate-methyl water dispersible granules is basically the same as that in Example 14, except that kasugamycin citrate is replaced by kasugamycin lactate.

[0160] 10 g of the above water-dispersible particles were added to 50 ml of deionized water, stirred for about 10 seconds, and allowed to stand for 5 minutes. The resulting solution was clear and had no obvious precipitation.

[0161] Example 16: Kasugamycin propionate-propamyl solution

[0162] 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 and stir evenly to obtain a clear, precipitate-free 7% kasugamycin propionate·propamocarb soluble solution.

[0163] Example 17: Kasugamycin acetate-propamyl solution

[0164] The preparation method of 7% kasugamycin acetate·propamoxic acid soluble solution was basically the same as that in Example 16, except that kasugamycin propionate was replaced by kasugamycin acetate. The soluble solution was clear and free of precipitation.

[0165] 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 considered as equivalent replacement methods and are included in the scope of protection of the present invention.

[0166] 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 list of elements includes not only those elements, but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

Claims

1. A pesticide composition, characterized in that: The composition contains active substance a and active substance b, 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; The active substance b is an alkyl polyamine organic acid salt and / or an alkyl guanidine organic acid salt fungicide, and the alkyl polyamine organic acid salt and / or the alkyl guanidine organic acid salt fungicide is selected from one or more of docodine, octamidine acetate and octamidine acetate.

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 2, characterized in that The active substance b is one or both of octamidine acetate and biguanide acetate.

4. A composition according to any one of claims 1 to 3, characterized in that The mass ratio of the active substance a to the active substance b is 0.1:10-10:0.

1.

5. The composition according to any one of claims 1 to 3, characterized in that The mass ratio of the active substance a to the active substance b is 0.1:1-2.5:

1.

6. A composition according to any one of claims 1 to 3, characterized in that The composition is a pesticide preparation, which contains pesticide-acceptable adjuvants.

7. The composition according to claim 6, characterized in that The dosage form of the pesticide preparation is a soluble preparation.

8. The composition according to claim 6 or 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 formulation.

9. 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.

10. The composition according to claim 9, 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.

11. The composition according to claim 9 or 10, 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.

12. The composition according to claim 9 or 10, characterized in that The dosage form of the composition is a soluble preparation.

13. The composition according to any one of claims 9 or 10, 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.

14. The composition according to claim 13, 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.

15. The composition according to any one of claims 13 or 14, 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.

16. The composition according to claim 13 or 14, 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 formulation.

17. Use of the composition according to any one of claims 1 to 16 in controlling plant diseases.

18. Use of the composition according to any one of claims 1 to 16 in the preparation of a plant disease control formulation.

19. 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.

20. 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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