Water dispersible granule containing bicyclopyrone and pyroxasulfone and preparation method thereof

Abstract

The invention provides a water dispersible granule containing bicyclopyrone and pyroxasulfone, which is prepared from the following components in percentage by mass: 20 to 50 percent of active pharmaceutical ingredients, 2 to 12 percent of dispersing agent, 2 to 8 percent of wetting agent, 5 to 20 percent of stabilizing agent and filler, the active ingredients comprise pyroxasulfone and bicyclopyrone or salts of the pyroxasulfone and the bicyclopyrone. The content of the bicyclopyrone-pyroxasulfone water dispersible granule provided by the invention is more than 35%, so that the dosage and the application frequency of herbicides are reduced, and the medicament cost is reduced. By optimizing the auxiliaries, the processing difficulty of the dosage form is greatly reduced, the dispersible tablet has the advantages of quick disintegration and high suspension rate, the product stability is improved, the dispersible tablet can tolerate thermal storage at 54 DEG C, the influence of environmental change in the transportation process is effectively solved, and the product quality problem of unstable thermal storage is avoided. And meanwhile, the method can tolerate different water qualities such as C water, D water, 3WHO water and the like, can be used in different countries and regions, and is beneficial to large-scale popularization and application.

Description

Technical Field

[0001] The invention relates to the technical field of pesticides, and in particular to a water-dispersible granule containing fluoropyraclostrobin and sulfonepyraclostrobin and a preparation method thereof. Background Art

[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 herbicide and is mainly used in crops such as corn, sugar beets, cereals (such as wheat and barley) to control broadleaf weeds and some grass weeds. It has a high control effect on large-seeded broadleaf weeds such as ragweed and Xanthium sibiricum, and has a good control effect on 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-isoxazole, is a new type of isoxazole herbicide. It is widely used in crops, mainly corn, cotton, peanuts, wheat, sunflowers and other crops. It can effectively prevent and control grass weeds such as Setaria, Digitaria, Echinochloa and broad-leaved weeds such as Amaranthus, Datura, Solanum, and Abutilon.

[0004] Herbicide varieties containing a single active ingredient often have defects to varying degrees in agricultural weed control, such as a narrow weed control spectrum, weeds are prone to develop resistance after continuous use, and frequent use will aggravate environmental pollution.

[0005] The synergistic effect of combining flupyralid and sulfonepyrazone can help expand the weed control spectrum, delay weed resistance, and reduce the number of times pesticides are used. However, flupyralid has a low melting point and unstable product quality. It is easily affected by environmental changes during sea transportation. It is prone to non-disintegration, reduced suspension rate, and poor thermal storage stability at high temperatures, which seriously affect the efficacy. During use, it is greatly affected by different water qualities. For example, it is intolerant to 3 WHO water, which is not conducive to the use and promotion of the product. Therefore, there are currently no water-dispersible granules for the combination of flupyralid and sulfonepyrazone 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 fluorine-pyraclostrobin and sulfonepyraclostrobin and a preparation method thereof. The prepared water-dispersible granule containing fluorine-pyraclostrobin and sulfonepyraclostrobin has high stability.

[0007] The present invention provides a water dispersible granule containing fluoropyrazone and sulfonepyrazone, which comprises, by weight content:

[0008] Active pharmaceutical ingredient 20% to 50%, dispersant 2% to 12%, wetting agent 2% to 8%, stabilizer 5% to 20%, filler;

[0009] The active ingredients include pyraclostrobin and fluazifop or their salts.

[0010] The invention uses sulfonepyraclostrobin and flupyraclostrobin or their salts as active ingredients, and successfully prepares water-dispersible granules containing flupyraclostrobin and sulfonepyraclostrobin by optimizing auxiliary agents.

[0011] The salt of fluazifop-dipraz may be one or more of an ammonium salt, a sodium salt, and a potassium salt.

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

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

[0014] The mass ratio of flupyralid or its salt to sulfonepyrazone 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 invention, the mass content of flupyralid or its salt is preferably 24% or 20%, and the mass content of sulfonepyrazone is preferably 15% or 17%.

[0015] The pure product of flupyralidone has the appearance of white powder, the melting point is 65.3℃ (the actual melting point is 57.3~59.7℃), the vapor pressure (20℃): <3.75×10 -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):<5.3×10 -8 (pH 4.9), <1.7×10 -8 (pH7.2), <1.7×10 -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] The appearance of pure sulfonepyraclostrobin is a white solid with a slight special odor; melting point: 130.7℃; boiling point: 362.4℃; vapor pressure: 2.4×10-6 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℃); Solubility in water 3.49mg / L (20℃); Stability: DT in pH 5, 7, 9 buffer at 25℃ 50 >1 year.

[0017] Judging from the properties of the two, there is a risk that a single dose of fluazifop-butyl will not disintegrate during hot storage and the suspension rate will decrease. Therefore, it is difficult to mix the two to make water-dispersible granules. The original drug particles will agglomerate after hot storage, and the flocculation suspension rate will decrease.

[0018] The present invention greatly reduces the processing difficulty of the dosage form and improves the stability of the dosage form by limiting the auxiliary agent system with the best matching degree among the above-mentioned components, especially by reacting the flupyralid technical into salt and screening and combining the three components of the dispersant and the wetting agent, and has the advantages of good dispersibility and high suspension rate, and effectively solves 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, methyl naphthalene sulfonate formaldehyde condensate sulfate, naphthalene sulfonate formaldehyde condensate sodium salt, methylene naphthalene sulfonate sodium dibutyl naphthalene sulfonate formaldehyde condensate, sodium N-methyl fatty acyl taurine, alkyl naphthalene sulfonate formaldehyde condensate, alkylphenol polyoxyethylene ether formaldehyde condensate sulfate, alkyl sulfonic acid formaldehyde polymer and sodium lignin sulfonate.

[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 invention, the mass content of the dispersant is 8%, 9%, 10%, 11% or 12%.

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

[0022] The first dispersant preferably includes one or more of sodium lignin sulfonate and sodium polyacrylate.

[0023] The second dispersant preferably includes one or more of alkylnaphthalenesulfonate formaldehyde condensate and alkylsulfonic acid formaldehyde polymer.

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

[0025] In some preferred embodiments of the present invention, the first dispersant is selected from polyacrylic acid sodium salt; the second dispersant is selected from alkyl sulfonic acid formaldehyde polymer.

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

[0027] In some preferred embodiments of the present invention, the dispersant comprises sodium lignin sulfonate and alkylnaphthalene sulfonate formaldehyde condensate. The mass content of the sodium lignin sulfonate is preferably 3% to 6%, and the mass content of the alkylnaphthalene sulfonate formaldehyde condensate is preferably 3% to 6%.

[0028] In some preferred embodiments of the present invention, the dispersant includes 6% sodium lignin sulfonate and 3% alkyl naphthalene sulfonate formaldehyde condensate.

[0029] In some preferred embodiments of the present invention, the dispersant includes 3% sodium lignin sulfonate and 6% alkyl naphthalene sulfonate formaldehyde condensate.

[0030] In some preferred embodiments of the present invention, the dispersant comprises polyacrylic acid sodium salt and alkyl sulfonic acid formaldehyde polymer. The mass content of the polyacrylic acid sodium salt 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 invention, the dispersant includes 2% polyacrylic acid sodium salt and 6% alkyl sulfonic acid formaldehyde polymer.

[0032] In some preferred embodiments of the present invention, the dispersant includes 7% polyacrylic acid sodium salt and 5% alkyl sulfonic acid formaldehyde polymer.

[0033] In some preferred embodiments of the present invention, the dispersant includes 3% polyacrylic acid sodium salt and 6% alkyl sulfonic acid formaldehyde polymer.

[0034] The preferred use of the above dispersants helps the product to disintegrate quickly in water and helps the product to be evenly dispersed in water.

[0035] Preferably, the wetting agent preferably includes one or more of sodium dodecyl sulfate, sulfo fatty acid methyl ester, sodium tetradecyl sulfate, sodium dodecylbenzene sulfonate, sodium alkyl naphthalene sulfonate, sodium α-olefin sulfonate, olefin and maleic anhydride polymer, alkylphenol polyoxyethylene ether sodium sulfate, sodium diisobutylnaphthalene sulfonate, sodium diisooctyl succinate sulfonate, fatty acid sulfates and fatty acid ester sulfates.

[0036] More preferably, the wetting agent includes one or more of sodium diisobutylnaphthalene sulfonate, olefin and maleic anhydride polymer, and more preferably, 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 includes one or more of corn starch, urea, CMC, ordinary white carbon black, and diammonium hydrogen phosphate, and more preferably includes 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 invention, the stabilizer includes diammonium phosphate and corn starch.

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

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

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

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

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

[0046] The present invention also provides a method for preparing the water dispersible granules containing fluoropyrazone and sulfonepyrazone, comprising the following steps:

[0047] S1) mixing fluazifop or its salt, pyraclostrobin, a dispersant, a wetting agent, a stabilizer and a filler uniformly, and crushing to obtain a fine powder;

[0048] S2) The fine powder is mixed with water and kneaded, and then extruded and granulated, and dried to obtain water dispersible granules containing fluoropyraclostrobin and sulfonepyraclostrobin.

[0049] Preferably, the flupyralidone is first reacted to form a salt, and the flupyralidone salt, sulfonepyralidone, a dispersant, a wetting agent, a stabilizer and a filler are uniformly mixed.

[0050] The above-mentioned pulverization can be a pulverization method well known to those skilled in the art, including but not limited to ultrafine airflow pulverization, grinding, etc. Ultrafine airflow pulverization is preferred.

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

[0052] The obtained fine powder is then subjected to secondary mixing. Specifically, the fine powder is mixed with water, kneaded, and then extruded into granules.

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

[0054] Finally, dry it.

[0055] The drying temperature is preferably 45 to 55°C.

[0056] Compared with the prior art, the present invention provides a water-dispersible granule containing fluopicolide and sulfonepyraclostrobin, which comprises, by mass content, 20% to 50% of active pharmaceutical ingredients, 2% to 12% of dispersant, 2% to 8% of wetting agent, 5% to 20% of stabilizer, and filler; the active ingredients include sulfonepyraclostrobin and fluopicolide or their salts.

[0057] The content of flupyralidone-sulfonepyraclostrobin water dispersible granules provided by the present invention exceeds 35%, which is conducive to reducing the amount of herbicide used and the frequency of application, thereby reducing the cost of the medicine. The present invention greatly reduces the processing difficulty of the dosage form by optimizing the auxiliary agent, has the advantages of fast disintegration and high suspension rate, and improves the stability of the product, can withstand 54°C hot storage, effectively solves the impact of environmental changes during transportation, and avoids the product quality problem of unstable hot storage. At the same time, the present invention can tolerate different water qualities such as C water, D water, 3WHO water, etc., meets the use of different countries and regions, and is conducive to large-scale promotion and application. DETAILED DESCRIPTION

[0058] In order to further illustrate the present invention, the water dispersible granules containing fluorine pyraclostrobin and sulfone pyraclostrobin provided by the present invention and the preparation method thereof are described in detail below in conjunction with the examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the invention.

[0059] All raw materials of the present invention have no particular limitation on their sources, and can be purchased from the market or prepared according to conventional methods known to those skilled in the art.

[0060] Examples 1-7

[0061] First, flupyralidone and sodium bicarbonate are reacted to form salt, then flupyralidone salt, sulfonepyralidone, dispersant, wetting agent, stabilizer and filler are uniformly mixed, and ultrafine air flow pulverization is performed to obtain fine powder with a particle size of 400-800 meshes, the obtained fine powder is subjected to secondary mixing, the obtained fine powder is mixed with water and then kneaded, the amount of water added can be 16%-22% of the total mass of the material, and after kneading, extrusion granulation is performed, and the obtained particles are dried at 45-55°C to obtain water-dispersible granule products of flupyralidone and sulfonepyralidone.

[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 Example 1-7, and the raw materials and amounts are shown in Table 1.

[0065] Table 1

[0066]

[0067]

[0068] The contents in Table 1 are by mass.

[0069] Performance Testing

[0070] The performance of the products obtained in the above examples and comparative examples was tested, and the results are shown in Table 2. Among them, for different water qualities (C water: hardness 500 mg / L, pH = 7.0-8.0; 3WHO water: hardness 1026 mg / L, pH = 6.0-7.0), the suspension rate was tested according to CIPAC MT184, the sieving (wet sieving test) was tested according to CIPAC MT185, the persistent foaming was tested according to CIPAC MT47.2, and the hot storage stability was measured according to the requirements for solid preparations in GB / T19136.

[0071] Disintegration is measured by the length of disintegration time, which is generally defined as qualified if it is less than 3 minutes. The measurement method is as follows: at 25°C, add 0.5 g of sample particles into a 100 mL stoppered measuring cylinder (height 22.5 cm, inner diameter 28 mm) filled with 90 mL of distilled water. Hold the middle of the measuring cylinder and rotate it uniformly along the center at a speed of 8 r / min until the sample is completely disintegrated in the water. Record the time, which is the disintegration time.

[0072] It can be seen from the data in Table 2 that, compared with the comparative example, the water dispersible granules prepared in the examples have improved the stability of the preparations and shortened the disintegration time by optimizing the auxiliary agents.

[0073] Among them, the suspension rate of the water-dispersible granules prepared in Examples 2, 3, 4, 6, and 7 before and after hot storage still maintained a high level of about 95%, no fine powder was screened, the hot storage stability was good, the disintegration time was fast, and the persistent foaming was relatively low; the quality of Examples 1 and 5 before and after hot storage was slightly worse than that of Examples 2, 3, 4, 6, and 7, and the quality was slightly worse after hot storage.

[0074] In Examples 2, 3, 4, 6, and 7, when the preferred adjuvant is selected, the performance of the water dispersible granules obtained is similar when the content of the active ingredient of the drug changes within the preferred ratio range, which shows that the drug content has little effect on the performance of the dosage form when the preferred adjuvant composition and content are used. It can be seen from Examples 1 and 5 that 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, and 7, which shows that the composition and content of the preferred adjuvant of the present invention have a significant improvement effect on the performance of the composite water dispersible granules of flupyradone and its salts and sulfonepyraclostrobin, while the single adjuvant in the comparative example has no improvement effect.

[0075] Table 2 Product properties of water dispersible granules prepared by compounding flupyrazone and its salts with sulfonepyraclostrobin

[0076]

[0077]

[0078] Field trials

[0079] The experiment was conducted in a soybean field of a farmer in the suburbs of Weifang City, Shandong Province. The pesticide compositions of Examples 1-8 and Comparative Examples 1-4 were sprayed in different planting areas. The application rate of the pesticide composition was 24 g.ai / mu, and the planting area of ​​each pesticide composition was 30 m 2 , diluted 3000 times with water during application, and water was used to replace the pesticide composition as a blank treatment. Except for applying the pesticide composition according to the above scheme, the other planting conditions in each planting area were exactly the same. 30 days after the herbicide was applied, the weeds in the planting area were identified and counted, and the control effect was calculated according to formula (A). The results are shown in Table 3.

[0080]

[0081] Table 3 Efficacy experimental data

[0082]

[0083] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A water dispersible granule containing fluoropyralidone and sulfonepyralidone, comprising, by mass content: Active pharmaceutical ingredient 20% to 50%, dispersant 2% to 12, wetting agent 2% to 8%, stabilizer 5% to 20%, filler; The active ingredients include pyraclostrobin and fluazifop or their salts.

2. The water dispersible granules containing fluorine-containing pyraclostrobin and sulfonepyraclostrobin according to claim 1, characterized in that: The mass ratio of fluazifop or its salt to sulfamethoxazole is 1:(0.01-90).

3. The water dispersible granules containing fluorine-containing pyraclostrobin and sulfonepyraclostrobin according to claim 1, characterized in that: The dispersant includes one or more of styrene acrylic acid copolymer sodium salt, polyacrylic acid sodium salt, methyl naphthalene sulfonic acid formaldehyde condensate sulfate, naphthalene sulfonic acid formaldehyde condensate sodium salt, methylene naphthalene sulfonate sodium dibutyl naphthalene sulfonic acid formaldehyde condensate, sodium N-methyl fatty acyl taurine, alkyl naphthalene sulfonate formaldehyde condensate, alkylphenol polyoxyethylene ether formaldehyde condensate sulfate, alkyl sulfonic acid formaldehyde polymer and sodium lignin sulfonate.

4. The water dispersible granules containing fluorine-containing pyraclostrobin and sulfonepyraclostrobin according to claim 1, characterized in that: The dispersant includes a first dispersant and a second dispersant; The first dispersant is selected from one or more of sodium lignin sulfonate and sodium polyacrylic acid salt; The second dispersant is selected from one or more of alkylnaphthalene sulfonate formaldehyde condensates and alkyl sulfonic acid formaldehyde polymers.

5. The water dispersible granules containing fluorine-pyraclostrobin and sulfonepyraclostrobin according to claim 4, characterized in that: The first dispersant is selected from sodium lignin sulfonate; the second dispersant is selected from alkyl naphthalene sulfonate formaldehyde condensate; Alternatively, the first dispersant is selected from polyacrylic acid sodium salt; and the second dispersant is selected from alkyl sulfonic acid formaldehyde polymer.

6. The water dispersible granules containing fluorine-pyraclostrobin and sulfonepyraclostrobin according to any one of claims 4 to 5, characterized in that: The mass ratio of the first dispersant to the second dispersant is 2:1 to 1:

3.

7. The water dispersible granules containing fluorine-containing pyraclostrobin and sulfonepyraclostrobin according to any one of claims 1 to 6, characterized in that: The wetting agent includes one or more of sodium dodecyl sulfate, sulfo fatty acid methyl ester, sodium tetradecyl sulfate, sodium dodecylbenzene sulfonate, sodium alkylnaphthalene sulfonate, sodium α-olefin sulfonate, olefin and maleic anhydride polymer, alkylphenol polyoxyethylene ether sodium sulfate, sodium diisobutylnaphthalene sulfonate, sodium diisooctyl succinate sulfonate, fatty acid sulfates and fatty acid ester sulfates.

8. The water dispersible granules containing fluorine-pyraclostrobin and sulfonepyraclostrobin according to any one of claims 1 to 7, characterized in that: The stabilizer includes one or more of corn starch, urea, CMC, ordinary white carbon black, and diammonium hydrogen phosphate.

9. The water dispersible granules containing fluorine-pyraclostrobin and sulfonepyraclostrobin according to any one of claims 1 to 8, characterized in that: The filler includes one or more of talc, calcined kaolin, kaolin and diatomaceous earth.

10. The method for preparing the water dispersible granules containing fluorinated pyraclostrobin and sulfonepyraclostrobin according to any one of claims 1 to 9, comprising the following steps: S1) mixing fluazifop or its salt, pyraclostrobin, a dispersant, a wetting agent, a stabilizer and a filler uniformly, and crushing to obtain a fine powder; S2) The fine powder is mixed with water and kneaded, and then extruded and granulated, and dried to obtain water dispersible granules containing fluoropyraclostrobin and sulfonepyraclostrobin.

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