A water dispersible granule containing topramezone and fentrazamide and a method for preparing the same

Abstract

The present application provides a kind of water dispersible granules containing fluorine pyroquilon and tolfenpyrad, including: 20%~50% of pharmaceutical active ingredient, 2%~12% of dispersing agent, 2%~8% of wetting agent, 5%~20% of stabilizer, filler by mass content;The active ingredient includes tolfenpyrad and fluorine pyroquilon or its salt.The water dispersible granules of fluorine pyroquilon tolfenpyrad provided by the present application contains more than 35%, which is beneficial to reduce the amount of herbicide and the frequency of application, so as to reduce the cost of reagent.The present application greatly reduces the processing difficulty of dosage form by selecting auxiliary agent, has the advantages of fast disintegration, high suspension rate, improves the stability of product, can tolerate 54 DEG C heat storage, effectively solves the influence of environmental change in transportation process, avoids the quality problem of unstable product in heat storage.At the same time, the present application can tolerate C water, D water, 3 WHO water and other different water quality, meet the use of different countries and regions, is beneficial to wide range of popularization and application.

Description

Technical Field

[0001] This invention relates to the field of pesticide technology, and in particular to a water-dispersible granule containing flupyrazole and sulfonylpyrazole, and its preparation method. Background Technology

[0002] Bicyclopyrone, chemical name: (1RS,5SR)-4-hydroxy-3-{2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyridylcarbonyl}bicyclo[3.2.1]oct-3-en-2-one, belongs to the triketone class of herbicides. It is mainly used on crops such as corn, sugar beets, and cereals (such as wheat and barley) to control broadleaf weeds and some grass weeds. It has high efficacy against large-seeded broadleaf weeds such as ragweed and cocklebur, and good efficacy against glyphosate-resistant weeds.

[0003] Pyroxasulfone, chemical name: 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-isoxaazole, is a novel isoxazole herbicide with a wide range of applications, mainly used on crops such as corn, cotton, peanuts, wheat, and sunflowers. It can effectively control grass weeds such as foxtail, barnyardgrass, and barnyardgrass, as well as broadleaf weeds such as amaranth, datura, solanum, and velvetleaf.

[0004] Herbicides containing a single active ingredient often have varying degrees of drawbacks in agricultural weed control, such as a narrow spectrum of weed control, the tendency for weeds to develop resistance after continuous use, and the potential for increased environmental pollution from repeated applications.

[0005] The synergistic effect of combining flupyrazole and sulfonylpyrazole helps broaden the weed control spectrum, delay weed resistance, and reduce the number of pesticide applications. However, flupyrazole has a low melting point, resulting in unstable product quality. During sea transport, it is easily affected by environmental changes, and high temperatures can lead to non-disintegration, reduced suspension rate, and poor thermal stability, severely impacting efficacy. Furthermore, its application is significantly affected by different water qualities; for example, it is intolerant to 3WHO water, hindering its use and promotion. Therefore, there are currently no water-dispersible granules combining flupyrazole and sulfonylpyrazole on the market. Summary of the Invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a water-dispersible granule containing fluopyram and sulfonylpyrazole and a method for preparing the same, wherein the prepared water-dispersible granule containing fluopyram and sulfonylpyrazole has high stability.

[0007] This invention provides a water-dispersible granule containing flupyrazole and sulfonylpyrazole, comprising, by mass content:

[0008] pharmaceutically active ingredient 20-50%, dispersing agent 2-12%, wetting agent 2-8%, stabilizer 5-20%, filler;

[0009] The active ingredient includes pyroxasulfone and benzofluor or a salt thereof.

[0010] The present application successfully prepares water dispersible granules containing benzofluor and pyroxasulfone by using pyroxasulfone and benzofluor or a salt thereof as active ingredients and preferred adjuvants.

[0011] The salt of benzofluor can be one or more of ammonium salt, sodium salt, and potassium salt.

[0012] Salifying benzofluor helps to increase the melting point of the active ingredient, thereby improving the stability of the preparation.

[0013] The mass content of the pharmaceutically active ingredient is preferably 20-50%, more preferably 30-40%.

[0014] The mass ratio of benzofluor or a salt thereof to pyroxasulfone is preferably 1:(0.01-90), more preferably 1:(0.1-1), and further preferably 1:(0.5-0.9). In some specific embodiments of the present application, the mass content of benzofluor or a salt thereof is preferably 24% or 20%, and the mass content of pyroxasulfone is preferably 15% or 17%.

[0015] Benzofluor pure product is white powder with a melting point of 65.3°C (actual detection of melting point is 57.3-59.7°C), vapor pressure (20°C): <3.75x10 -8 mmHg; solubility in water (g / L, 25°C): 38 (pH 4.9), 119 (pH 7.2), 119 (pH 9.2); solubility in organic solvents (g / L, 25°C): acetone >500, dichloromethane >500, ethyl acetate >500, hexane 8.9, methanol >500, octanol 91, toluene 500; Henry constant (25°C, Pa·m 3 / mol): <5.3x10 -8 (pH 4.9), <1.7x10 -8 (pH 7.2), <1.7x10 -8 (pH 9.2); octanol / water partition coefficient (log Kow) (25°C): 0.25 (pH 5), -1.2 (pH 7), -1.9 (pH 9); dissociation constant (pKa) (20°C): 3.06.

[0016] Pyroxasulfone pure product is a white solid with a slight special odor; melting point: 130.7°C; boiling point: 362.4°C; vapor pressure: 2.4x10-6 Pa (25°C); n-octanol / water partition coefficient: log POW = 2.39 (25°C, pH 8.7); density: 1.6 g / cm 3 (21.2°C); solubility in water: 3.49 mg / L (20°C); stability: DT50 = 1.2 years in pH 5, 7, 9 buffer at 25°C. 50 > 1 year.

[0017] From the properties of both, there is a risk of not disintegrating and reducing the suspension rate of flumioxazine single agent after heat storage, so it is difficult to prepare two mixed formulations as water dispersible granules. After heat storage, the original particles will appear agglomeration, flocculation and suspension rate reduction.

[0018] The present application greatly reduces the processing difficulty of the dosage form, improves the stability of the dosage form, has the advantages of good dispersibility and high suspension rate by limiting the matching degree of the above-mentioned auxiliary system, especially by reacting flumioxazine into a salt and screening and combining the three components of dispersant and wetting agent, effectively solving the problems of poor storage stability of the sample and flocculation.

[0019] Preferably, the dispersant includes one or more of styrene acrylic acid copolymer sodium salt, polyacrylic acid sodium salt, methylnaphthalene sulfonic acid formaldehyde condensate sulfate, naphthalene sulfonic acid formaldehyde condensate sodium salt, methylene naphthalene sulfonic acid sodium dibutyl naphthalene sulfonic acid formaldehyde condensate, N-methyl fatty acyl taurine sodium, alkyl naphthalene sulfonate formaldehyde condensate, alkyl phenol polyoxyethylene ether formaldehyde condensate sulfate, alkyl sulfonic acid formaldehyde polymer and sodium lignosulfonate.

[0020] The mass content of the dispersant is preferably 2% to 12%, more preferably 5% to 12%, and further preferably 8% to 12%. In some specific embodiments of the present application, the mass content of the dispersant is 8%, 9%, 10%, 11% or 12%.

[0021] The present application preferably uses a composite dispersant. Preferably, the dispersant includes a first dispersant and a second dispersant.

[0022] The first dispersant preferably includes one or more of sodium lignosulfonate and polyacrylic acid sodium salt.

[0023] The second dispersant preferably includes one or more of alkyl naphthalene sulfonate formaldehyde condensate and alkyl sulfonic acid formaldehyde polymer.

[0024] In some preferred embodiments of the present application, the first dispersant is selected from sodium lignosulfonate; and the second dispersant is selected from alkyl naphthalene sulfonate formaldehyde condensate.

[0025] In some preferred embodiments of the present application, the first dispersing agent is selected from sodium polyacrylate; and the second dispersing agent is selected from alkyl naphthalene sulfonate formaldehyde condensate.

[0026] Preferably, the mass ratio of the first dispersing agent to the second dispersing agent is 2:1 to 1:3. More preferably, the mass ratio of the first dispersing agent to the second dispersing agent is 2:1, 1:1, 1:2 or 1:3.

[0027] In some preferred embodiments of the present application, the dispersing agent comprises sodium lignosulfonate and alkyl naphthalene sulfonate formaldehyde condensate. The mass content of the sodium lignosulfonate is preferably 3% to 6%, and the mass content of the alkyl naphthalene sulfonate formaldehyde condensate is preferably 3% to 6%.

[0028] In some preferred embodiments of the present application, the dispersing agent comprises 6% sodium lignosulfonate and 3% alkyl naphthalene sulfonate formaldehyde condensate.

[0029] In some preferred embodiments of the present application, the dispersing agent comprises 3% sodium lignosulfonate and 6% alkyl naphthalene sulfonate formaldehyde condensate.

[0030] In some preferred embodiments of the present application, the dispersing agent comprises sodium polyacrylate and alkyl sulfonic acid formaldehyde polymer. The mass content of the sodium polyacrylate is preferably 2% to 7%, and the mass content of the alkyl sulfonic acid formaldehyde polymer is preferably 5% to 6%.

[0031] In some preferred embodiments of the present application, the dispersing agent comprises 2% sodium polyacrylate and 6% alkyl sulfonic acid formaldehyde polymer.

[0032] In some preferred embodiments of the present application, the dispersing agent comprises 7% sodium polyacrylate and 5% alkyl sulfonic acid formaldehyde polymer.

[0033] In some preferred embodiments of the present application, the dispersing agent comprises 3% sodium polyacrylate and 6% alkyl sulfonic acid formaldehyde polymer.

[0034] The above dispersing agent preferably helps the product to disintegrate rapidly in water and helps the product to be uniformly dispersed in water.

[0035] Preferably, the wetting agent preferably comprises one or more of sodium dodecyl sulfate, sulfonated fatty acid methyl ester, sodium myristyl sulfate, sodium dodecyl benzene sulfonate, sodium alkyl naphthalene sulfonate, sodium a-olefin sulfonate, olefin and butene dianhydride polymer, sodium alkyl phenol polyoxyethylene ether sulfate, sodium diisobutyl naphthalene sulfonate, sodium diisooctyl sulfosuccinate, fatty acid sulfate and fatty acid ester sulfate.

[0036] More preferably, the wetting agent comprises one or more of sodium diisobutyl naphthalene sulfonate, olefin and maleic anhydride polymer. Further preferably, the wetting agent comprises olefin and maleic anhydride polymer.

[0037] The mass content of the wetting agent is preferably 2% to 8%, more preferably 3% to 5%, and further preferably 4%.

[0038] The stabilizer preferably comprises one or more of corn starch, urea, CMC, common white carbon black, diammonium hydrogen phosphate. More preferably, the stabilizer comprises a combination of diammonium hydrogen phosphate and corn starch.

[0039] The mass content of the stabilizer is preferably 5% to 20%, more preferably 15% to 20%, and most preferably 20%.

[0040] In some preferred embodiments of the present application, the stabilizer comprises diammonium hydrogen phosphate and corn starch.

[0041] The mass ratio of the diammonium hydrogen phosphate and corn starch is preferably 1:0.2-5, and more preferably 1:1.

[0042] In some preferred embodiments of the present application, the stabilizer comprises 10% of diammonium hydrogen phosphate and 10% of corn starch.

[0043] Preferably, the filler comprises one or more of talc, calcined kaolin, kaolin, and diatomite. More preferably, the filler comprises a combination of talc and calcined kaolin.

[0044] The mass content of the filler is preferably 100% of the system.

[0045] In some preferred embodiments of the present application, the filler comprises 15% of talc and the balance of calcined kaolin.

[0046] The present application also provides a preparation method of the above-mentioned water dispersible granules of fluroxypyr and pyroxasulfone, comprising the following steps:

[0047] S1) uniformly mixing fluroxypyr or a salt thereof, pyroxasulfone, a dispersant, a wetting agent, a stabilizer, and a filler, and then crushing to obtain fine powder;

[0048] S2) kneading the above-mentioned fine powder after mixing with water, and then extruding and granulating, and then drying to obtain water dispersible granules of fluroxypyr and pyroxasulfone.

[0049] Preferably, first, fluroxypyr is reacted to form a salt, and then fluroxypyr salt, pyroxasulfone, a dispersant, a wetting agent, a stabilizer, and a filler are uniformly mixed.

[0050] The pulverization can be a pulverization method known to those skilled in the art, including but not limited to ultrafine jet pulverization, grinding, etc. Preferably, the pulverization is ultrafine jet pulverization.

[0051] The particle size of the fine powder after pulverization is preferably 400-800 mesh.

[0052] The obtained fine powder is then subjected to secondary mixing, specifically, the fine powder is mixed with water and then subjected to kneading and then extrusion granulation.

[0053] The amount of water added is preferably 16-22% of the total mass of the material.

[0054] Finally, drying is performed.

[0055] The temperature of the drying is preferably 45-55°C.

[0056] Compared with the prior art, the present application provides a water dispersible granule containing fluridone and pyroxasulfone, which comprises, in terms of mass content, 20-50% of a pharmaceutical active ingredient, 2-12% of a dispersant, 2-8% of a wetting agent, 5-20% of a stabilizer, and a filler; the active ingredient comprises pyroxasulfone and fluridone or a salt thereof.

[0057] The water dispersible granule containing fluridone and pyroxasulfone provided by the present application has a content of more than 35%, which is beneficial to reducing the amount of herbicide and the frequency of application, thereby reducing the cost of the medicament. The present application greatly reduces the processing difficulty of the dosage form by using preferred adjuvants, has the advantages of fast disintegration and high suspension rate, and improves the stability of the product, can withstand 54°C heat storage, effectively solves the influence of environmental changes during transportation, and avoids the problem of unstable product quality during heat storage. Meanwhile, the present application can withstand different water qualities such as C water, D water, and 3 WHO water, meets the use of different countries and regions, and is beneficial to wide range of popularization and application. DETAILED DESCRIPTION

[0058] In order to further illustrate the present application, the water dispersible granule containing fluridone and pyroxasulfone and the preparation method thereof provided by the present application are described in detail below in combination with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present application, and are not a limitation on the claims of the present application.

[0059] All raw materials of the present application are not particularly limited in source, and can be purchased on the market or prepared according to conventional methods known to those skilled in the art.

[0060] Examples 1-7

[0061] Flumioxazin is first reacted with sodium bicarbonate to form a salt, then the flumioxazin salt, benzenesulfonamide, dispersing agent, wetting agent, stabilizer, and filler are mixed uniformly, and are subjected to ultra-micro air flow pulverization to obtain fine powder with a particle size of 400-800 mesh. The obtained fine powder is subjected to secondary mixing, and the obtained fine powder is mixed with water and then is subjected to kneading. The amount of water added can be 16%-22% of the total mass of the material. After kneading, the obtained particles are subjected to extrusion granulation, and the obtained particles are dried at 45-55°C to obtain the flumioxazin and benzenesulfonamide water dispersible granule product.

[0062] The raw materials and amounts used in each example are shown in Table 1.

[0063] Comparative Examples 1-4

[0064] The preparation process is the same as that of Examples 1-7, and the raw materials and amounts used are shown in Table 1.

[0065] Table 1

[0066]

[0067]

[0068] The content in Table 1 is the mass content.

[0069] Performance detection

[0070] The performance of the products prepared in the above examples and comparative examples is detected, and the results are shown in Table 2 below. Different water qualities (C water: hardness of 500 mg / L, pH = 7.0-8.0; 3 WHO water: hardness of 1026 mg / L, pH = 6.0-7.0), suspension rate is detected according to CIPAC MT184, screening (wet screening test) is detected according to CIPAC MT185, persistent foaming property is detected according to CIPAC MT47.2, and thermal storage stability is detected according to the requirements for solid preparations in GB / T19136.

[0071] Disintegration is indicated by the length of the disintegration time, and generally, less than 3 min is qualified. The detection method is as follows: at 25°C, 0.5 g of sample particles are added to a 100 mL stoppered cylinder (cylinder height 22.5 cm, inner diameter 28 mm) containing 90 mL of distilled water, the middle part of the cylinder is clamped, and the cylinder is rotated at a speed of 8 r / min along the center at a uniform speed until the sample is completely disintegrated in water. The time is recorded, which is the disintegration time.

[0072] As can be seen from the data in Table 2, compared with the comparative examples, the water dispersible granules prepared in the examples all improve the stability of the preparation and shorten the disintegration time by optimizing the adjuvants.

[0073] Among them, the water dispersible granules prepared in examples 2, 3, 4, 6, 7 still maintain a high level of about 95% in suspension rate before and after heat storage, no fine powder appears in screening, the heat storage stability is good, the disintegration time is faster, and the persistent foaming property is relatively lower; the quality ratio of examples 1, 5 before and after heat storage is slightly worse than that of examples 2, 3, 4, 6, 7, and the quality after heat storage is slightly worse.

[0074] In the case of selecting preferred adjuvants, the properties of the water dispersible granules obtained when the content of the pharmaceutical active ingredient is changed within the preferred proportion range in examples 2, 3, 4, 6, 7 are similar, which shows that when the preferred adjuvant components and contents are used, the content of the pharmaceutical active ingredient has less effect on the performance of the dosage form. As can be seen from examples 1, 5, the performance of the obtained water dispersible granules is improved, and the degree of improvement is slightly lower than that of examples 2, 3, 4, 6, 7, which shows that the components and contents of the preferred adjuvants of the present application have a significant improvement effect on the performance of the water dispersible granules of fluridone and its salt and furilazole, and the single adjuvant in the comparative example does not have the improvement effect.

[0075] Table 2 Performance of the water dispersible granules prepared by compounding fluridone and its salt and furilazole

[0076]

[0077]

[0078] Field experiment

[0079] The experiment was arranged in a soybean field of a farmer in the suburb of Weifang City, Shandong Province, and the pesticide compositions of examples 1-8 and comparative examples 1-4 were sprayed and applied in different planting areas. The application amount of the pesticide compositions was 24 g.a.i / acre, and the area of the planting area for testing each pesticide composition was 30 m 2 . When applied, water was diluted 3000 times, and water was used as a blank treatment instead of the pesticide composition. In addition to applying the pesticide composition according to the above scheme, the other planting conditions in the planting area were exactly the same. After 30 days of spreading herbicide, the weeds in the planting area were identified and counted, the control effect was calculated according to formula (A), and the results are shown in Table 3.

[0080]

[0081] Table 3 Experimental data of the efficacy

[0082]

[0083] The above examples are only used to help understand the method of the present application and its core idea. It should be pointed out that for ordinary skilled persons in the technical field, some improvements and modifications can be made to the present application without departing from the principles of the present application, and these improvements and modifications also fall within the protection scope of the claims of the present application.

Claims

1. A water dispersible granule containing flurochloridone and bensulfuron-methyl, comprising, in mass content, 20-50% of a pharmaceutical active ingredient, 2-12% of a dispersant, 2-8% of a wetting agent, 5-20% of a stabilizer, and a filler; wherein the active ingredient comprises bensulfuron-methyl and flurochloridone or a salt thereof; the first dispersant is selected from sodium lignosulfonate; and the second dispersant is selected from alkyl naphthalene sulfonate formaldehyde condensate; or the first dispersant is selected from polyacrylic acid sodium salt; and the second dispersant is selected from alkyl sulfonic acid formaldehyde polymer; the mass ratio of the first dispersant to the second dispersant is 2:1-1:

3. The mass ratio of the flurochloridone or a salt thereof to the bensulfuron-methyl is 1: (0.01-90). The wetting agent comprises one or more of sodium dodecyl sulfate, sulfobenzene methyl ester, sodium tetradecyl sulfate, sodium dodecyl benzene sulfonate, sodium alkyl naphthalene sulfonate, sodium a-olefin sulfonate, olefin and butene anhydride polymer, alkyl phenol polyoxyethylene ether sodium sulfate, sodium diisobutyl naphthalene sulfonate, sodium diisooctyl sulfosuccinate, fatty acid sulfate, and fatty acid ester sulfate. The stabilizer comprises one or more of corn starch, urea, CMC, common white carbon black, diammonium hydrogen phosphate. The filler comprises one or more of talc, calcined kaolin, kaolin, and diatomite. 6.A method for preparing the water dispersible granule containing flurochloridone and bensulfuron-methyl according to any one of claims 1-5, comprising the following steps: S1) uniformly mixing flurochloridone or a salt thereof, bensulfuron-methyl, a dispersant, a wetting agent, a stabilizer, and a filler, and then crushing to obtain a fine powder; and S2) mixing the fine powder with water, kneading, extruding, and granulating, and then drying to obtain the water dispersible granule containing flurochloridone and bensulfuron-methyl.

2. The water dispersible granule of fluazacort and benfuracarb according to claim 1, characterized by, ​ 3. The water dispersible granule of fluazafop-butyl and fentrazamide according to any one of claims 1 to 2, characterized in that, ​ 4. The water dispersible granule of fluazafop-butyl and fentrazamide according to any one of claims 1 to 2, characterized in that, ​ 5. The water dispersible granule of fluazafop-butyl and fentrazamide according to any one of claims 1 to 2, characterized in that, ​ ​ ​ ​

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