A compound salt hydrochloride crystal form and its application

Abstract

The present application relates to a kind of crystal form I of agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyl oxo) pyran-3-yl amino-alpha-imino acetic acid hydrochloride and its amorphous substance, crystal form I shows good stability under high temperature and high humidity light environment, and can better meet the requirements of pesticide in production, processing and transportation and storage, and presents excellent effect in preparation processing and preparation stability, more can meet the demand of mixed agent processing and stable shelf life period.Simultaneously 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyl oxo) pyran-3-yl amino-alpha-imino acetic acid hydrochloride amorphous substance shows unexpected effect in plant disease control effect.

Description

Technical Field

[0001] This invention belongs to the field of agricultural technology, specifically relating to the crystal form and preparation method of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate. Background Technology

[0002] 5-Amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid (CAS 6980-18-3) belongs to the aminoglycoside class of antibiotics. Since its discovery in the 1960s and 1970s, 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid has been widely used to control various diseases in a variety of crops, including rice, potatoes, cabbage, and melons. Due to its excellent control efficacy and environmentally friendly characteristics, 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid is currently a major biological pesticide product for crop disease control. 5-Amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid is extremely unstable in alkaline environments, and it is also a hygroscopic compound. Considering factors such as transportation, storage, and quality control, a more stable and less hygroscopic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid product is desirable for manufacturing and processing companies.

[0003] At the outset of the discovery of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid, Ikekawa T et al. briefly investigated the crystal structure of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid hydrobromide (The Journal of Antibiotics, Jan 1966, 19(1):49-50). CN115925475A reported the use of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid phosphate to supplement phosphorus while controlling pathogens. CN108822167A reports 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate and its white needle-like or flaky crystals. CN106083951B and CN109666051B report the extraction of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate from water by dissolution and crystallization with solvents such as acetone, methanol, and ethanol.

[0004] Although existing technologies have disclosed methods for preparing high-purity 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate, the crystalline products obtained by different crystallization methods often differ, exhibiting significant variations in physicochemical properties and corresponding performance in formulation processing. Therefore, a stable crystalline product of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate that is conducive to formulation processing and storage is a goal pursued by biopesticide companies. Summary of the Invention

[0005] In view of the above-mentioned problems in the prior art, the present invention provides a technical solution to solve the above problems.

[0006] According to one aspect of the present invention, a crystal form I of the agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate is provided, wherein the characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I, expressed in 2θ values ​​± 0.2°, using Cu-Kα radiation, include 8.66, 10.11, 11.05, and 13.3.

[0007] Optionally, for crystal form I, the characteristic diffraction peaks of the X-ray powder diffraction pattern expressed in 2θ value ± 0.2° using Cu-Kα radiation also include one or both of 13.92 and 15.56, and preferably one or both of 16.47 and 17.29.

[0008] Optionally, crystal form I grain size D 90 The value is 10μm-200μm, preferably 15μm-150μm, and more preferably 20μm-120μm.

[0009] Optionally, crystal form I is granular or rod-shaped.

[0010] Differential scanning calorimetry (DSC) showed that the 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form I exhibited a continuous endothermic signal in the range of 110±2℃ to 210±2℃, and an endothermic signal at 226±2℃. In terms of the endothermic peak height (or peak trough), crystal form I exhibited a strong endothermic process at 226±2℃ and a weak endothermic process in the range of 110±2℃ to 210±2℃.

[0011] Thermogravimetric analysis (TGA) showed that the crystal form I had a weight loss of less than 5% during heating from 100±2℃ to 220±2℃ and a weight loss of less than 15.5% during heating from 220±2℃ to 255±2℃.

[0012] According to another aspect of the invention, the present invention provides an amorphous 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate.

[0013] Optionally, the amorphous material has the following characteristics: Figure 6 The X-ray powder diffraction peaks shown are as follows.

[0014] DSC showed that the amorphous material had endothermic signals at 73±2℃ and 187±2℃.

[0015] TGA results showed that the amorphous material had a weight loss of less than 9% when heated to 175±2℃, and a weight loss of less than 15% when heated from 175±2℃ to 255±2℃.

[0016] Optionally, the amorphous 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt has a plate-like structure.

[0017] Optionally, the amorphous material D 90The value is 10μm-200μm, preferably 15μm-150μm, and more preferably 20μm-120μm.

[0018] According to another aspect of the invention, a technical grade or parent drug is provided, said technical grade or parent drug containing the crystal form I and / or amorphous material described above.

[0019] Based on total mass, the content of crystalline form I and / or amorphous substances in the technical grade drug shall not be less than 65%, such as not less than 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%; preferably, not less than 85%, 90%, or 95%.

[0020] Based on total mass, the content of crystalline form I and / or amorphous substances in the parent drug is not less than 5% or 10%, such as not less than 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%; preferably not less than 85%, 90%, or 95%.

[0021] According to another aspect of the invention, a formulation or pesticide composition is provided, the formulation or pesticide composition containing the crystal form I and / or amorphous substances and adjuvants described above.

[0022] Optionally, the crystal form I and / or amorphous material constitutes at least 0.001% by weight in the formulation or pesticide composition.

[0023] Optionally, the dosage form of the formulation is selected from any one of the following: powder, granules, large granules, fine granules, microparticles, microcapsule granules, wettable powder, oil-dispersible powder, water-dispersible granules, emulsion 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, spreading oils, ultra-low volume liquids, ultra-low volume microcapsule suspensions, emulsifiable concentrates, latexes, dispersible liquids, pastes, concentrated gels, water emulsions, oil emulsions, microemulsions, greases, suspensions, microcapsule suspensions, oil suspensions, suspension emulsions, seed-treated dispersible powders, seed-treated soluble powders, seed-treated liquids, seed-treated emulsions, seed-treated suspensions, suspension seed coating agents, and seed-treated microcapsule suspensions. Preferably, the crystalline form I or amorphous solids of the present invention exhibit excellent processability and solid application control efficacy in pesticide solid formulations. Specifically, the crystalline form I or amorphous solids of the present invention are used in wettable powders or powder formulations; wherein the particle size D of the crystalline form I and / or amorphous solids in the powder or wettable powder formulation is...90 The preferred particle size is D, ranging from 5μm to 80μm. 90 The range is 10μm-50μm, or 15μm-45μm, or 20μm, 30μm, 40μm, 60μm and 70μm.

[0024] According to another aspect of the present invention, the application of the crystal form I, the amorphous material, the technical grade or parent material, or the formulation or pesticide composition described above in the process of controlling plant diseases is provided.

[0025] According to another aspect of this application, the use of the crystal form I, the amorphous material, the technical grade or parent material, or the formulation or pesticide composition described above in the preparation of plant disease control agents is provided.

[0026] The positive and progressive effects of this invention are as follows:

[0027] The applicant believes that the crystalline form I provided in this application possesses excellent stability, exhibits virtually no hygroscopicity, and remains stable under conditions of light, high temperature, high humidity, and accelerated processes, effectively extending the shelf life of the pesticide and better meeting the requirements for pesticide production, processing, transportation, and storage. Simultaneously, crystalline form I has also achieved good technical results in plant disease control. Unexpectedly, the amorphous form demonstrated the best effect in plant disease control, with even more outstanding results in agricultural end-use applications. Attached Figure Description

[0028] Figure 1 The image shows the 1H-NMR spectrum of compound crystal form I.

[0029] Figure 2 The image shows the X-ray powder diffraction (XRPD) pattern of crystal form I, where the horizontal axis represents 2θ (°) and the vertical axis represents intensity (count).

[0030] Figure 3 The image shows the 1H-NMR spectrum of compound crystal form II.

[0031] Figure 4 The image shows the X-ray powder diffraction (XRPD) pattern of crystal form II, where the horizontal axis represents 2θ (°) and the vertical axis represents intensity (count).

[0032] Figure 5 The hydrogen nuclear magnetic resonance (1H-NMR) spectrum of the amorphous material;

[0033] Figure 6 The image shows the X-ray powder diffraction (XRPD) pattern of the amorphous material, where the horizontal axis represents 2θ (°) and the vertical axis represents the intensity (count).

[0034] Figure 7Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) spectra of crystal form I;

[0035] Figure 8 The differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) spectra for crystal form II are shown.

[0036] Figure 9 Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) spectra of amorphous materials;

[0037] Figure 10 The polarized light microscopy (PLM) pattern of crystal form I is shown.

[0038] Figure 11 The image is a polarized light microscopy (PLM) analysis image of crystal form II;

[0039] Figure 12 Polarizing microscopy (PLM) images of amorphous objects;

[0040] Figure 13 Image showing the particle size distribution (PSD) of crystal form I;

[0041] Figure 14 Image for particle size distribution determination (PSD) of crystal form II;

[0042] Figure 15 The dynamic moisture adsorption-desorption analysis (DVS) spectrum of crystal form I;

[0043] Figure 16 The results are from the stability test of crystal form I;

[0044] Figure 17 The results of the potted plant antibacterial experiment are shown below. a-1 is a front view of the leaf of the blank control, a-2 is a back view of the leaf of the blank control, b-1 is a front view of the leaf of the crystal form II powder experiment, b-2 is a back view of the leaf of the crystal form II powder experiment, and c-1 is a front view of the leaf of the crystal form I powder experiment, c-2 is a back view of the leaf of the crystal form I powder experiment. Figure 17 d-1 is a front view of the leaf in the amorphous powder experiment, and d-2 is a back view of the leaf in the amorphous powder experiment. Detailed Implementation

[0045] The term "solvent" refers to those crystal forms of the compounds described in this application that coordinate with solvent molecules (such as water, organic solvents such as formic acid, toluene, etc.) to form complexes. Hydrates are a specific form of solvate in which coordination with water occurs. For example, a solvate can be a hydrate.

[0046] The term "raw material" refers to the product obtained during the production process, which consists of active ingredients and related impurities, and may include a small amount of additives if necessary.

[0047] The term "mother drug" refers to the product obtained during the production process, which consists of the active ingredient and related impurities, and may contain small amounts of necessary additives and appropriate diluents.

[0048] The term "formulation" refers to a stable product made from pesticide technical (mother drug) and suitable adjuvants, or processed by methods such as bio-fermentation and plant extraction.

[0049] The term "adjuvant" refers to any single or multiple components, other than the active ingredient, added to a pesticide product that do not possess pesticide activity or the function of the active ingredient, but can or help to improve or enhance the physicochemical properties of the pesticide product.

[0050] The term "plant disease" refers to the phenomenon where, during the growth and development of a plant, its growth and development are significantly hindered due to infection by other organisms and adverse abiotic factors. This results in pathological changes both internally and externally, in terms of physiology and tissue structure, leading to illness or even death, and consequently, reduced yield and deteriorated quality. In this application, "plant disease" specifically refers to diseases caused by infection of plants by other organisms, including but not limited to fungi (such as cucumber downy mildew caused by *Pseudomonas columbinis*) or bacteria (such as bacterial angular leaf spot in cucurbits).

[0051] The terms “approximately”, “about”, and “basically” refer to numerical variations within the normal experimental or measurement error range. For example, “basically” represents an error of no more than 15%, preferably no more than 10%.

[0052] In one specific embodiment, the 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt crystal form I described in this application is a hydrate.

[0053] In one specific embodiment, the characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt, expressed as 2θ values ​​± 0.2° using Cu-Kα radiation, include 8.66, 10.11, 11.05, and 13.3. Preferably, the characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I, expressed as 2θ values ​​± 0.2° using Cu-Kα radiation, include 8.66, 10.11, 11.05, 13.3, 13.92, and 15.56. Preferably, the characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I, expressed as 2θ values ​​± 0.2°, include 8.66, 10.11, 11.05, 13.3, 13.92, and 15.56. The characteristic diffraction peaks of the X-ray powder diffraction pattern include 8.66, 10.11, 11.05, 13.3, 13.92, 15.56, 16.47, and 17.29; more preferably, the characteristic diffraction peaks of the X-ray powder diffraction pattern expressed in 2θ values ​​± 0.2° include 8.66, 10.11, 11.05, 13.3, 13.92, 15.56, 16.47, 17.29, 18.59, and 19.25, or include 8.66, 10.11, 11.05, 13.3, 13.92, 15.56, 16.47, 17.29, 18.59, 19.25, 20.41, and 20.78.

[0054] In one specific embodiment, the crystal form I of the compound 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt described in this application is granular or rod-shaped. To meet the needs of actual production, facilitate solid-liquid filtration, and facilitate subsequent processing of pesticide solid formulations, the particle size D of crystal form I is... 90 The particle size is 10μm-200μm. Preferably, the crystal form I has a grain size D. 90 The particle size ranges from 15μm to 150μm and from 20μm to 120μm, for example, crystal form I with a particle size D. 90 It can also be 10, 15, 25, 35, 45, 55, 65, 75, 85, 95, 100, 110, 130, 140, 150, 160, 170, 180, 190 or 200 μm.

[0055] In one specific embodiment, differential scanning calorimetry (DSC) shows that the 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form I has a continuous endothermic signal in the range of 110±2℃ to 210±2℃, and an endothermic signal at 226±2℃; in terms of the endothermic peak height (or peak trough), crystal form I is a strong endothermic process at 226±2℃, and a weak endothermic process in the range of 110±2℃ to 210±2℃.

[0056] Thermogravimetric analysis (TGA) showed that the crystal form I had a weight loss of less than 5% during heating from 100±2℃ to 220±2℃ and a weight loss of less than 15.5% during heating from 220±2℃ to 255±2℃.

[0057] In one specific embodiment, the 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt prepared according to this application is an amorphous product with the following properties: Figure 6 The XRPD diffraction peak pattern shown is shown.

[0058] DSC analysis showed that the amorphous material had endothermic signals at 73±2℃ and 187±2℃.

[0059] The TGA showed that the amorphous material had a weight loss of less than 9% during heating to 175±2°C and a weight loss of less than 15% during the process from 175±2°C to 255±2°C.

[0060] Optionally, the amorphous 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt has a plate-like structure.

[0061] Optionally, the amorphous particle size D 90 The particle size is 10μm-200μm. Preferably, the crystal form I has a grain size D. 90 The particle size ranges from 15μm to 150μm and from 20μm to 120μm, for example, crystal form I with a particle size D. 90 It can also be 10, 15, 25, 35, 45, 55, 65, 75, 85, 95, 100, 110, 130, 140, 150, 160, 170, 180, 190 or 200 μm.

[0062] In one embodiment, the crystalline solid can be prepared by methods such as dissolution-backdipation, liquid-gas phase diffusion, single-solvent room temperature suspension, single-solvent high temperature suspension, binary solvent forward drop, single-solvent cooling, and binary solvent cooling.

[0063] Preferably, crystal form I is prepared by methods such as dissolution-back-dropping or liquid-gas diffusion, and is not limited to the evidence presented in the preparation examples of this application. Crystal form I of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate as described in this invention is also prepared by other crystallization methods such as single-solvent room temperature suspension, single-solvent high temperature suspension, binary solvent forward drop, single-solvent cooling, and binary solvent cooling.

[0064] Preferably, the amorphous material is prepared by freeze-drying, which can be selected as a circulating freeze dryer or a medium freeze dryer (such as dry ice freeze dryer or nitrogen freeze dryer).

[0065] Preferably, the dissolution-precipitation back-tickling method includes the following steps: adding an aqueous solution containing 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate dropwise to a poor solvent, precipitating the solid, suspending it for 10-120 minutes, and filtering to obtain the solid. The dropwise addition process may be stirred or not stirred, with a stirring rate of 20-120 rpm; the poor solvent is dioxane or ethylene glycol dimethyl ether.

[0066] Preferably, the liquid-gas phase diffusion method includes the following steps: weighing a certain amount of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate solution dissolved in a good solvent, placing the clear solution in a poor solvent atmosphere, allowing it to stand at room temperature until solid precipitates, and then filtering. The good solvent is water or formamide, and the poor solvent is trifluoroethanol.

[0067] In one specific embodiment, the technical grade or parent drug provided in this application contains the crystal form I or amorphous substance described in this application. By total mass, the content of crystal form I in the technical grade is not less than 65%, such as not less than 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%; preferably, not less than 85%, 90%, or 95%.

[0068] Based on total mass, the content of crystalline form I and / or amorphous substances in the parent drug is not less than 5% or 10%, such as not less than 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%; preferably not less than 85%, 90%, or 95%.

[0069] In one specific embodiment, the formulation or pesticide composition provided in this application contains the crystalline form I and / or amorphous substance described in this application. Preferably, the weight percentage of the crystalline form I and / or amorphous substance in the formulation is at least 0.001%, for example, the weight percentage of the crystalline form I and / or amorphous substance in the formulation is at least 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%. Preferably, the weight percentage of the crystalline form I and / or amorphous substance in the formulation is 0.1%-10%, 0.5-7%, or 1-5%.

[0070] In another embodiment, the use of the crystal form I, the amorphous material, the technical grade or parent material, or the formulation or pesticide composition described above in the preparation of a plant disease control agent is provided. Specific implementation examples:

[0072] All commercially available reagents and solvents were not further purified.

[0073] The sample testing in the examples was performed according to the following method.

[0074] 1. X-ray powder diffraction (XRPD)

[0075] The solid samples obtained in the experiment were analyzed using a Bruker D8 Advance X-ray powder diffractometer (Bruker, GER). The 2θ scanning angle ranged from 3° to 45°, the scanning step size was 0.02°, and the exposure time was 0.08 seconds. The testing method was Cu target Kα1 radiation, voltage 40 kV, current 40 mA, and a zero-background sample disk.

[0076] 2. Differential Scanning Calorimetry (DSC)

[0077] The differential scanning calorimeter was a TA Discovery 2500 (TA, US). 1-2 mg of sample was accurately weighed and placed in a perforated DSC Tzero sample pan. The sample was heated to the final temperature at a rate of 10 °C / min, with nitrogen purging at a rate of 50 mL / min.

[0078] 3. Thermogravimetric analysis (TGA)

[0079] The thermogravimetric analyzer was a TA Discovery 55 (TA, US). 2-5 mg of sample was placed in a pre-equilibrated open aluminum sample pan and automatically weighed inside the TGA furnace. The sample was heated to the final temperature at a rate of 10 °C / min, with nitrogen purging at 60 mL / min at the sample location and 40 mL / min at the balance location.

[0080] 4. Nuclear magnetic resonance analysis (1H NMR)

[0081] Several milligrams of solid sample were dissolved in dimethyl sulfoxide-d6 solvent and analyzed by nuclear magnetic resonance on a Bruker AVANCE NEO 400 (Bruker, GER).

[0082] 5. Polarizing Microscopy (PLM) Analysis

[0083] The polarizing microscope used was a Nikon Ci-POL (Nikon, JP). A small amount of sample was placed on a glass slide, and a suitable lens was selected to observe the sample morphology.

[0084] 6. Particle size distribution determination (PSD)

[0085] The laser particle size analyzer used was a Mastersizer 3000 (Malvern Panalytical, UK). 20 mg of sample was dispersed in 8 mL of dispersant. Sample dispersion units were added until the opacity reached 10-20%, at which point measurement began. The stirring speed was 2000 rpm for 10 seconds. The dispersant was ethanol, the scattering model was Mie, and the analysis model was general.

[0086] 7. Dynamic moisture adsorption-desorption analysis (DVS)

[0087] Dynamic moisture adsorption-desorption analysis was performed using DVS Intrinsic (SMS, UK). The test employed a gradient mode with humidity variations of 50%-95%-0%-50%. Within the 0% to 90% range, each gradient represented a 10% change in humidity. The gradient endpoint was determined using the dm / dt method, with a dm / dt value less than 0.002% maintained for 10 minutes as the endpoint, or each gradient maintained for a maximum of 180 minutes. After the test, XRPD analysis was performed on the samples to confirm whether the solid form had changed.

[0088] 8. Stability Study

[0089] (1) Influencing Factors Experiment

[0090] Weigh 20 mg of sample into a weighing bottle and place it open under high temperature (60℃), high humidity (25℃ / 92.5%RH) or light (25℃ / 4500Lux) conditions. Take samples at 7 and 15 days, observe the appearance, perform XRPD characterization and high performance liquid chromatography (HPLC) tests, and compare the results with those at 0 days.

[0091] (2) Accelerated stability test

[0092] Weigh 20 mg of sample into a weighing bottle, place it open under accelerated conditions (40℃ / 75% RH), and take samples at 7 and 15 days to observe the appearance, perform XRPD characterization and HPLC testing, and compare the results with those at 0 days.

[0093] 9. HPLC

[0094] The high-performance liquid chromatograph is model ACQUITY ARC-2489 (Waters, US);

[0095] Mobile phase: Acetonitrile:sodium dodecyl sulfonate solution = 1:4, v / v (pH adjusted to 2.5 with phosphoric acid); Sodium dodecyl sulfonate solution preparation: 0.8g sodium dodecyl sulfonate solid dissolved in 400ml ultrapure water;

[0096] Chromatographic column: CORTECS C18 4.6×150mm, 2.7μm

[0097] Detection wavelength: 210nm

[0098] Flow rate: 1.2 mL / min

[0099] Column temperature: 30℃

[0100] Injection volume: 5 μL

[0101] (I) Preparation Examples

[0102] Comparative Example 1: Preparation of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form II

[0103] A fermentation broth containing 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid is provided. Specifically, *Streptomyces aureus* is used as the producing strain, and the fermentation broth is obtained through multi-stage fermentation in a culture medium containing low-temperature soybean meal, soybean oil, yeast powder, liquid sugar, and other raw materials. Purification and crystallization are performed according to the method described in the example of CN106083951B, including fermentation broth pretreatment, ceramic membrane filtration, macroporous resin decolorization, and nanofiltration concentration. During crystallization, organic solvents such as acetone, methanol, ethanol, propanol, or isopropanol are added to prepare five solid crystalline products.

[0104] The above solid crystalline products were vacuum dried and then subjected to NMR and XRPD analysis. NMR showed that the solid crystalline products were all 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate. The NMR spectrum of the solid crystalline product obtained by crystallization with the organic solvent methanol is shown below. Figure 3As shown in the figure. XRPD results indicate that the above solid crystalline product is a crystal form, referred to as crystal form II. The XRPD pattern of the solid crystalline product crystallized by the organic solvent acetone is shown in the figure. Figure 4 As shown.

[0105] Comparative Example 2: Preparation of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form II

[0106] Using *Streptomyces simonii* as the producing strain, a fermentation broth was obtained through multi-stage fermentation in a culture medium containing low-temperature soybean meal, soybean oil, yeast powder, and liquid sugar. The broth was purified and crystallized according to the method described in the example of CN109666051B. Crystallization was performed by cooling crystallization or crystallization with the addition of organic solvents acetone or ethanol, resulting in three solid crystalline products. After vacuum drying at room temperature, the solid crystalline products were subjected to NMR and XRPD measurements. NMR showed that all the solid crystalline products were 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate. XRPD showed that the solid crystalline products had the same crystal form as those obtained in Comparative Example 1, all being crystal form II.

[0107] Example 1: Preparation of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form I

[0108] a) The fermentation broth containing 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetic acid was acidified with oxalic acid and then filtered.

[0109] b) Collect the filtrate, adsorb it with a strong acid cation exchange resin, and then elute it.

[0110] c) The ammonium chloride eluent is concentrated by nanofiltration and then further decolorized using activated carbon;

[0111] d) The decolorized solution is filtered and then concentrated under vacuum to obtain a vacuum concentrate;

[0112] e) Take 10 ml of the vacuum concentrate prepared in step d, add the concentrate dropwise to 20 times the volume of dioxane (a poor solvent) at room temperature, stir at 60 rpm, suspend for 30-40 min, and filter to obtain the precipitate;

[0113] f) The obtained precipitate was dried at room temperature to obtain a high-purity solid crystalline product. The solid crystalline product was analyzed by NMR and XRPD. The NMR spectra of the solid crystalline product were as follows: Figure 1As shown, it indicates that it is 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate, XRPD as Figure 2 As shown, this is called crystal form I.

[0114] Example 2: Preparation of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form I

[0115] A high-purity solid crystalline product was prepared according to step af of Example 1, except that the undesirable solvent was replaced with ethylene glycol dimethyl ether. The solid crystalline product was identified by NMR and XRPD as 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form I.

[0116] Example 3: Preparation of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate crystal form I

[0117] a) Take 250 mg of the dried solid crystalline product from Example 1;

[0118] b) Dissolve the solid crystalline product in 4 ml of water;

[0119] c) Take 1 ml of the solution from step b, place the concentrate in a trifluoroethanol atmosphere, and let it stand at room temperature until a solid precipitates out.

[0120] d) Remove the solution from the system with solid precipitate using a syringe, and perform NMR and XRPD tests on the solid sample. The results show that the solid sample is crystal form I of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate.

[0121] Example 4: Preparation of amorphous 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate

[0122] a) Take 100 mg of the dried solid crystalline product from Example 1;

[0123] b) Dissolve the solid crystalline product in 2 ml of water;

[0124] c) Freeze the solution from step b using dry ice and freeze-dry it in a freeze dryer for 1 day;

[0125] d) The freeze-dried product was analyzed by NMR and XRPD. The NMR results showed that it was 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate (e.g. Figure 5 As shown), XRPD results indicate that it is an amorphous material without obvious characteristic peaks (as shown). Figure 6 (As shown).

[0126] Example 5: Preparation of Powder

[0127] Approximately 70g of three dry solids—crystal form II, crystal form I, and amorphous solid—were prepared according to the methods of Comparative Example 1, Example 1, and Example 4, with contents of 98.1%, 98.7%, and 96.3%, respectively, and were used as the technical grade / parent drug for the formulation.

[0128] A small vertical sand mill and zirconium beads were used. Zhimo (Shanghai) New Material Technology Co., Ltd. pulverized the above-mentioned raw materials / master materials respectively, with 40g of zirconium beads used, a sand mill speed of 1500r / min, and a grinding time of 30min. After grinding, the zirconium beads and fine powder were separated.

[0129] PSD analysis showed that the particle size D90 of the three technical grade / master powders ranged from 36.6 μm to 40.2 μm.

[0130] Take 4g of each of the three raw materials / parent materials powders mentioned above, and mix the three powders with 96g of diatomaceous earth through a 200-mesh sieve before thoroughly mixing to prepare three powder formulations.

[0131] Example 6: Preparation of wettable powder

[0132] The dosage of each component in the wettable powder is shown in the table below:

[0133]

[0134] The wettable powder is prepared by the following steps:

[0135] 1) Take the fine powders of crystal form I and amorphous active ingredient / master drug prepared in Example 5 according to the table above, and set them aside for later use;

[0136] 2) Thoroughly mix copper hydroxide, sodium dodecyl sulfate, sodium lignosulfonate, silica, and diatomaceous earth, and then pulverize them using an ultrafine pulverizer to obtain the additive powder;

[0137] 3) Thoroughly mix the fine powder of the original drug / parent drug with the adjuvant powder prepared in step 2) to obtain a wettable powder.

[0138] (II) Basic Characterization of Crystal Forms

[0139] (1) 1H NMR analysis

[0140] NMR shows crystal form I (e.g.) Figure 1 As shown), crystal form II (as shown) Figure 3 (as shown) and amorphous objects (such as) Figure 5 All of them are 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate compounds.

[0141] (2) XRPD diffraction peak data analysis

[0142] The XRPD diffraction peak data of crystal form I of the compound 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt described in this application are shown in Table 1; the XRPD diffraction peak data of crystal form II are shown in Table 2.

[0143] Table 1. XRPD diffraction peak data for crystal form I.

[0144]

[0145]

[0146] As shown in Table 1, the main characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I using Cu-Kα radiation, expressed as 2θ values ​​± 0.2°, include 8.66, 10.11, 11.05, and 13.3, as well as any one or more characteristic diffraction peaks among 13.92, 15.56, 16.47, and 17.29. Specifically, they may include 8.66, 10.11, 11.05, 13.3, 13.92, and 15.56; or 8.66, 10.11, 11.05, 13.3, 16.47, and 17.29; or 8.66, 10.11, 11.05, 13.3, 13.92, 15.56, 16.47, and 17.29.

[0147] Table 2 XRPD diffraction peak data for crystal form II

[0148]

[0149] As shown in Table 2, the main characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form II using Cu-Kα radiation, expressed as 2θ values ​​± 0.2°, include 8.91, 10.03, 10.51, 12.12, 15.01, 16.40, 17.14, and 26.68. Compared with crystal form I, crystal form II does not contain characteristic diffraction peaks such as 8.66, 11.05, and 13.30, but contains characteristic diffraction peaks such as 8.91, 10.51, and 12.12.

[0150] according to Figure 6 It can be seen that the amorphous material prepared by freeze-drying has no significant diffraction peaks.

[0151] In summary, the preparation method of this invention yielded three solid products, namely crystal form I, crystal form II, and amorphous product. By comparing the XRPD patterns and diffraction peak data of crystal form I and crystal form II, it can be seen that they belong to different crystal forms.

[0152] (3) DSC and TGA analysis

[0153] The DSC and TGA spectra of crystal form I described in this application are as follows: Figure 7 As shown; the DSC and TGA spectra of crystal form II are as follows. Figure 8 As shown.

[0154] The DSC display shows that crystal form I has a continuous endothermic signal in the range of 110±2℃ to 210±2℃, and an endothermic signal at 226±2℃; in terms of the height (or valley) of the endothermic peak, crystal form I has a strong endothermic process at 226±2℃ and a weak endothermic process in the range.

[0155] TGA shows that the crystal form I has a weight loss of about 0.2% when heated to 100±2℃, a weight loss of less than 5% when heated from 100±2℃ to 220±2℃, and a weight loss of less than 15.5% when heated from 220±2℃ to 255℃±2℃.

[0156] The DSC analysis shows that crystal form II has a weak endothermic signal at 147±2℃ and a strong endothermic signal at 215±2℃. In terms of the endothermic peak height (or peak-valley), crystal form I has a strong endothermic process at 215±2℃ and a weak endothermic process at 147±2℃.

[0157] TGA shows that the crystal form II exhibits a weight loss of less than 6% during heating to 195±2°C and a weight loss of less than 15% during heating from 220±2°C to 250±2°C.

[0158] DSC showed that the amorphous material had endothermic signals at 73±2℃ and 187±2℃;

[0159] TGA results showed that the amorphous material had a weight loss of less than 9% when heated to 175±2℃, and a weight loss of essentially less than 15% when heated from 175±2℃ to 255±2℃.

[0160] (4) PLM and PSD analysis

[0161] PLM images show that crystal form I is predominantly granular (e.g., ...). Figure 10 (As shown); Particle size distribution analysis indicates that crystal form I has a particle size D 5064.2μm, D 90 119μm (e.g.) Figure 13 (As shown).

[0162] PLM images show that crystal type II is predominantly acicular (e.g., Figure 11 (As shown); Particle size distribution analysis indicates that crystal form II has a particle size D 50 24.7μm, D 90 It is 70.1 μm (e.g.) Figure 14 (As shown).

[0163] PLM images show amorphous materials as sheet-like (e.g.) Figure 12 As shown), particle size D 50 It is 30.2 μm.

[0164] (III) Powder Flowability

[0165] To verify the processing properties of different solid products, the flowability of the three fine powders prepared in Example 5 was tested. The flowability of the fine powders was determined according to the "angle of repose" method in the "Guidelines for Determination of Powder Flowability" issued by the National Pharmacopoeia Commission on December 19, 2022. The test was conducted with a fixed funnel height (10 cm), at room temperature and with a humidity of approximately 5%. The amount of fine powder used was 60 g. The experimental results are shown in Table 3.

[0166] Table 3 Evaluation of Powder Flowability

[0167] Fine powder information Angle of repose (°) Liquidity assessment Crystal type I fine powder 29 very good Crystal type II fine powder 41 generally amorphous fine powder 39 better

[0168] Table 3 shows that, under the same conditions, the pulverized crystalline form I and amorphous form exhibit better powder flowability than crystalline form II. This indicates that crystalline form I and amorphous form 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate are more favorable for subsequent processing in mixtures and formulations. Among them, crystalline form I 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate shows the best processing performance. Further investigations will be conducted on the hygroscopicity and stability of crystalline form I, crystalline form II, and amorphous form.

[0169] (iv) DVS Analysis

[0170] like Figure 15 As shown, crystal form I only increased in weight by 1.57% at 95% humidity, increased in weight by 0.40% at 80% humidity, and lost weight by 1.02% at 0% humidity, indicating that crystal form I has virtually no hygroscopicity and is a stable solid product even in high humidity environments.

[0171] In comparison, crystal form II showed a 2.2% weight gain due to moisture absorption at 95% humidity and a 0.74% weight gain at 80% humidity, exhibiting weak hygroscopicity under high humidity conditions; while amorphous materials showed the general hygroscopic characteristics of amorphous materials.

[0172] (V) Stability determination

[0173] Stability studies were conducted on crystal forms I and II under high temperature (60℃), high humidity (25℃ / 92.5% RH), light exposure (25℃ / 4500 Lux), and accelerated stabilization (40℃ / 75% RH) conditions. Samples were taken at 7 and 15 days to observe appearance, XRPD characterization, and HPLC testing, and the results were compared with those of the original samples. The results showed that crystal form I remained stable under high temperature, high humidity, light exposure, and accelerated stabilization conditions, specifically: no change in appearance, no crystal form transformation, and no significant change in chemical purity (as shown in Table 4). Figure 16 As shown in the figure, this indicates that crystal form I is a stable solid crystalline product.

[0174] The stability results of crystal form II showed that crystal form II maintained a stable appearance under 15 days of high temperature and high humidity testing. After 7 days of light exposure, the appearance changed from white to yellow, and after 15 days, the color changed to light brown, indicating that crystal form II is relatively unstable under continuous light exposure.

[0175] Table 4. Experimental results of different environmental influencing factors for crystal form I.

[0176]

[0177] (vi) Antibacterial effect of potted plants

[0178] 1. Preparation of cucumber downy mildew spore suspension

[0179] The fungus causing cucumber downy mildew was collected from naturally infected leaves in the Weinan Ecological Agriculture Demonstration Park. The collected diseased leaves were cleaned of the moldy layer on the underside of the lesions using a brush dipped in distilled water. The leaves were then placed in a dark incubator at 25℃ and 80% relative humidity for 16 hours to induce the production of fresh sporangia. The fresh sporangia were then brushed onto petri dishes containing distilled water and filtered twice to prepare a spore suspension (concentration 2×10⁻⁶). 5 -4×10 5 (pcs / mL), for later use.

[0180] 2. Indoor cultivation of cucumbers

[0181] Cucumbers (Xinong No. 58, 20 pots in total, 1 plant per pot) were planted in plastic pots with a diameter of 5cm. They were cultivated to a height of about 1 meter under the conditions of temperature of 20℃-28℃ (day and night), relative humidity of (90±5)%, and fluorescent light for 12 hours. Twelve cucumber seedlings with similar growth were selected as samples for subsequent experiments.

[0182] 3. Foliar preventative application of pesticides

[0183] Two leaves of similar height (measured from the soil surface) and approximately 5-8 cm wide were selected from each of 12 cucumber seedlings. The three mixed powders prepared in Example 5 were packaged into identical spray bottles and applied preventatively as powdered pesticides: two sprays were performed at a height of approximately 40 cm above the leaves. Each powder was sprayed on three seedlings and six leaves as a parallel experiment; the control group was sprayed only with diatomaceous earth powder. The leaves were marked and recorded accordingly (Group A was the control group, Group B contained crystalline form II powder, Group C contained crystalline form I powder, and Group D contained amorphous powder). After 48 hours of cultivation under the previous planting conditions, cucumbers were inoculated against downy mildew.

[0184] 4. Inoculation and therapeutic application for cucumber downy mildew

[0185] The prepared spore suspension was poured into a spray bottle and sprayed twice onto the selected leaves from a height of about 20 cm. Immediately after spraying, a transparent plastic bag was placed over the leaves and the bag was tied tightly. This process was repeated for inoculating 24 leaves on 12 cucumber seedlings with downy mildew. The transparent plastic bags were removed at 2, 6, and 10 hours post-inoculation, and the inoculated leaves were moistened with pure water via spraying. The bags were then reapplied. 24 hours after inoculation, a therapeutic application was performed using the same methods as preventative treatment (Group A: diatomaceous earth powder; Group B: powder containing crystal form II; Group C: powder containing crystal form I; Group D: powder containing amorphous substances). Fifteen days after the therapeutic application, the leaves were washed, and the condition of the experimental leaves was observed, recorded, and statistically analyzed.

[0186] The disease is graded based on the area of ​​the lesions, and the grading criteria are as follows:

[0187] Grade 0: Leaves show no disease spots;

[0188] Grade 1: The lesion area accounts for less than 5% of the total leaf area;

[0189] Grade 3: Lesions cover 6-10% of the total leaf area;

[0190] Level 5: Lesions cover 11-25% of the total leaf area;

[0191] Level 7: Lesions cover 26-50% of the total leaf area;

[0192] Level 9: The lesion area accounts for more than 50% of the total leaf area;

[0193] Disease index = {[∑(number of diseased leaves at each treatment level × corresponding level value)] / total number of leaves surveyed × 9} × 100;

[0194] Prevention and control effect (%) = [(disease index of blank control - disease index of drug treatment) / disease index of blank control group] × 100;

[0195] The results of the four sets of experiments are shown in Table 5, and some of the effects are illustrated below. Figure 17 As shown.

[0196] Table 5. Effects of foliar control

[0197] Group Disease index Prevention and control efficacy (%) A 96.30 -- B 48.15 50.00 C 22.22 79.63 D 11.11 88.46

[0198] Surprisingly, based on plant disease index and control efficacy, there were significant differences in the control effects of crystalline form I, crystalline form II, and amorphous form. The powder containing the amorphous form showed the best control effect, followed by the powder containing crystalline form I. This indicates that different crystalline and amorphous forms of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate may differ in terms of drug release, plant absorption, and antibacterial ability. The amorphous form and crystalline form I of 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate showed better plant disease control effects than crystalline form II.

[0199] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and intent of the present invention should be included within the scope of protection of the present invention.

Claims

1. A pesticide technical or parent material, characterized in that, Based on the total mass of the pesticide technical or technical material, the content of crystalline form I and / or its amorphous form of the agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt in the pesticide technical or technical material shall not be less than 65%; The pesticide technical or parent material contains the crystalline form I and / or amorphous form of the agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate. The characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I, expressed as 2θ value ± 0.2°, include 8.66, 10.11, 11.05, and 13.

3. The amorphous material has X-ray powder diffraction peaks as shown in Figure 6.

2. The pesticide technical or parent material according to claim 1, characterized in that, Based on the total mass of the pesticide technical or parent product, the content of the crystalline form I and / or its amorphous components of the agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt in the pesticide technical or parent product shall not be less than 70%.

3. The pesticide technical or parent material according to any one of claims 1-2, characterized in that, The crystalline form I and / or amorphous particle size D of the agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt in the pesticide technical or parent material. 90 The range is 10μm-200μm.

4. The pesticide technical or parent material according to any one of claims 1-2, characterized in that, The crystalline form I and / or amorphous particle size D of the agricultural antibiotic 5-amino-2-methyl-6-(2,3,4,5,6-hydroxycyclohexyloxo)pyran-3-ylamino-α-iminoacetate salt in the pesticide technical or parent material. 90 The range is 15μm-150μm.

5. The pesticide technical or parent material according to claim 1, characterized in that, The characteristic diffraction peaks of the X-ray powder diffraction pattern of crystal form I, expressed as 2θ value ± 0.2°, using Cu-Kα radiation, also include any one or more of the following characteristic diffraction peaks: 13.92, 15.56, 16.47, and 17.

29.

6. The pesticide technical or parent material according to claim 1, characterized in that, Differential scanning calorimetry (DSC) of the amorphous material showed endothermic signals at 73±2 ºC and 187±2 ºC.

7. The pesticide technical or parent material according to claim 1, characterized in that, Thermogravimetric analysis (TGA) results showed that the amorphous material had a weight loss of less than 9% during heating to 175±2ºC and less than 15% during the process from 175±2ºC to 255±2ºC.

8. The pesticide technical or parent material according to claim 1, characterized in that, The amorphous material has a sheet-like structure.

9. A pesticide composition, characterized in that, The pesticide composition contains any of the pesticide technical or parent material as described in claims 1-8.

10. The pesticide composition according to claim 9, characterized in that, The pesticide composition is a formulation, and the formulation dosage form is selected from any one of the following: powder, large granules, fine granules, microparticles, microcapsule granules, wettable powder, oil-dispersible powder, water-dispersible granules, emulsion granules, effervescent granules, dispersible tablets, effervescent tablets, sustained-release blocks, sustained-release tubes, sustained-release granules, soluble powder, soluble granules, soluble tablets, aqueous solutions, soluble gels, oils, spreading oils, ultra-low volume liquids, ultra-low volume microcapsule suspensions, emulsifiable concentrates, latexes, dispersible liquids, pastes, concentrated gels, water emulsions, oil emulsions, microemulsions, greases, suspensions, microcapsule suspensions, oil suspensions, suspension emulsions, seed treatment dispersible powders, seed treatment soluble powders, seed treatment liquids, seed treatment emulsions, and seed treatment suspensions.

11. The pesticide composition according to claim 9, characterized in that, The pesticide composition is a formulation, and the formulation is selected from any one of granules, slow-release agents, soluble agents, and suspension seed coating agents.

12. The pesticide composition according to claim 9, characterized in that, The pesticide composition is a formulation, and the formulation is a seed treatment microcapsule suspension.

13. The pesticide composition according to claim 10, characterized in that, The pesticide composition is a formulation, and the formulation is in the form of a powder or a wettable powder.

14. The pesticide composition according to claim 10 or 13, wherein the particle size D of crystal form I and / or amorphous components in the powder or wettable powder is... 90 The range is 5μm-80μm.

15. The application of the pesticide technical or parent material according to any one of claims 1-8, or the pesticide composition according to any one of claims 9-14, in the control of plant diseases, wherein the plant disease is cucumber downy mildew.

16. The use of the pesticide technical or parent material according to any one of claims 1-8, or the formulation or pesticide composition according to any one of claims 9-14, in the preparation of a plant disease control agent, wherein the plant disease is cucumber downy mildew.

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