RU2138525C1 - Composition showing biological activity and aqueous agent for plant protection - Google Patents

Abstract

FIELD: organic chemistry, agriculture. SUBSTANCE: invention describes the composition showing biological activity and containing an organic solvent. As the biologically active substance the composition has difficultly soluble substance, its solubility is less 0.5 g/100 ml and the statistical copolymer of the formula:

Description

 The invention relates to compositions with biological activity and an aqueous plant protection product.

 A known composition with biological activity, in particular with antibacterial activity, containing an antibacterial substance, a water-insoluble polymer, in particular a copolymer of vinylpyrrolidone and a long-chain olefin, a plasticizer and an organic solvent (see US patent N 5 082656, IPC: A 61 K 31/79 , A 61 K 31/74, 1992).

 A disadvantage of the known composition is that in the case of the presence in it of an active substance with poor water solubility, the aqueous working preparation obtained from it exhibits unsatisfactory storage stability.

 The objective of the invention is to improve the stability during storage of liquid compositions with biological activity containing active substances with poor water solubility.

где x означает число 0-16, а n и m больше 1,
с содержанием сложного винилового эфира 5-90 % от веса сополимера, причем весовое соотношение между биологически активным веществом и сополимером составляет от 1 : 0,2 до 1 : 10, и дополнительно композиция содержит по крайней мере одно поверхностно-активное вещество, доля которого в композиции составляет 0,001 - 10 вес.частей на 1 вес.часть биологически активного вещества.This problem is solved by the proposed composition with biological activity containing a biologically active substance, a vinyl pyrrolidone copolymer and an organic solvent, due to the fact that it contains a sparingly soluble substance having a water solubility of less than 0.5 g / 100 ml, as a vinyl pyrrolidone copolymer - random copolymer of the formula

where x is the number 0-16, and n and m are greater than 1,
with a vinyl ester content of 5-90% by weight of the copolymer, the weight ratio between the biologically active substance and the copolymer being from 1: 0.2 to 1: 10, and the composition further comprises at least one surfactant, the proportion of which is the composition is 0.001 to 10 parts by weight per 1 part by weight of a biologically active substance.

 The proposed composition may further comprise a diluent.

 Non-ionic, cationic and anionic emulsifiers can be used as surfactants according to the invention, such as, for example, polyoxyethylene fatty acid ester, fatty alcohol polyoxyethylene ether, alkylaryl polyglycol ether, alkyl sulfonates, alkyl sulfates, alkyl aryl sulfonates and aryl sulfates. Examples of such surfactants are provided in the Fidler, X.P. "Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende Gebiete", ed. Cantor Aulendorf, 1981. They can be used separately or in any combination. Particularly suitable surfactants according to the invention are ionic surfactants, such as, for example, sodium dodecyl sulfate and sodium dioctyl sulfosuccinate, as well as the monoethanolamine salt of dodecylbenzenesulfonic acid.

 An additional object of the invention is an aqueous plant protection product.

 Known aqueous plant protection product containing a composition with biological activity, water and target additives (see USSR patent N 1 456 077, IPC: A 01 N 25/10, 1989).

 The proposed aqueous plant protection product differs from the known one in that it contains the above composition as a composition with biological activity.

 The proposed composition may also contain conventional target additives in amounts up to 100 weight. parts by weight. part of the active substance. In the case of an aqueous plant protection product, the target additives of the composition may be stabilizers that improve the storage stability of the preparation at low temperature, and adhesives that improve the adhesion to the plant of the aqueous spray solution obtained from the preparations. Examples of stabilizers are urea, glycerin and propylene glycol. Carboxymethyl cellulose, natural and synthetic polymers, such as gum arabic, polyvinyl alcohol, polyvinyl acetate, and natural phospholipids, such as cephalins and lecithins, as well as synthetic phospholipids, are preferably used as adhesion-enhancing substances.

 The content of organic solvent in the proposed composition is up to 100 weight. parts by weight. part of the biologically active substance.

 As the solvent, all polar and nonpolar organic solvents commonly used for such purposes can be used, such as, for example, propylene glycol, polyethylene glycol with different molecular weights, ketones, such as methyl isobutyl ketone and cyclohexanone, amides, such as dimethylformamide, cyclic compounds, such as N-methylpyrrolidone, N-methylcaprolactam and butyrolactone, strongly polar solvents like dimethyl sulfoxide, aromatic hydrocarbons like xylene, esters such as acetate propyl glycol monomethyl ether, adipic acid dibutyl ester, acetic acid hexyl ester, acetic acid heptyl ester, tri-n-butyl citric acid ester and phthalic acid di-n-butyl ester, in addition, glycol ethers for example, propylene glycol methyl ether, as well as alcohols, such as ethanol, propanol, butanol and normal and isostructured amyl alcohol, benzyl alcohol, tetrahydrofuryl alcohol and 1-methoxy-2-propanol.

 Particularly preferred are N-methylpyrrolidone, dimethylformamide, dimethyl sulfoxide, propylene glycol, polyethylene glycol, ethanol and iso-propanol.

 In principle, the proposed composition may contain any biologically active substance with a water solubility of <0.5 g / 100 ml, in particular <0.1 g / 100 ml, preferably <0.01 g / 100 ml, at room temperature. As examples of such biologically active substances, there are known pharmaceutically active dihydropyridines, such as, for example, nimodipine, nifedipine, nitrendipine, nizoldipine, darodipine, isradipine, felodipine.

 Examples of fungicidal substances are 2-anilino-4-methyl-6-cyclopropyl-pyrimidine, 2 ', 6'-dibromo-2-methyl-4'-trifluoromethoxy-4'-trifluoro-methyl-1,3-tizol-5- carboxanilide, 2,6-dichloro-M- (4-trifluoro-methylbenzyl) benzamide, (E) -2-methoxyimino-N-methyl-2- (2-phenoxyphenyl) -acetamide, 8-hydroxyquinoline sulfate, complex E) -2- {2- [6- (2-cyanophenoxy) pyrimidin-4-yloxy] phenyl} -3-methoxyacrylic acid methyl ester, (E) -methoxyimino [alpha- (o-tolyloxy) - methyl ester o-tolyl] acetic acid, 2-phenylphenol, commercial products aldimorph, ampropylphos, anilazine, azaconazole, benalaxyl, b nodanil, benomyl, binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate, butiobat, captafol, captan, carbendazim, carboxin, chinomethionat (kvinometionat), chloroneb, hloropikrin, chlorothalonil, chlozolinate, kufraneb, cymoxanil, cyproconazole, tsiprofuram, dichlorophen , diclobutrazole, diclofluanide, diclomesine, dicloran, dietofencarb, diphenoconazole, dimethyrimol, dimetomorph, diniconazal, dinocap, diphenylamine, dipyrithione, ditalimphos, dithianone, dodinone, ediphenol, ediphenol, ediphenol, etazolefenol l, fenfuram, fenitropan, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoromid, fluquinconazole, fluzilazol, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminum, fthalide, fuberidazole, furalaxyl, furmetsikloks, guazatin, hexachlorobenzene, hexaconazole, gimexazole, imazalil, imibenconazole, iminoktadin, iprobenfos, iprodion, isoprothiolan, kazugamitsin, mankopper, mankozeb, maneb, mepanipyrim, metaroxam, metaxamaz, metaxamaz, metaxamaz, metacamaz, metacamaz, methacamoxam ulfovax, miklobutanyl, nickel dimethyldithiocarbamate, nitrotal-isopropyl, nuarimol, ofurantse, oxadixyl, oxamocarb, oxycarboxin, pefurazoate, penconazole, pencicuron, fosfifen, pimaricin, propylene, polyoxin phosphonofenazole, pyroxinofibenofrazene , pyrimethanil, pyroquilone, quintozene, tebuconazole, teclofthalam, teknazen, tetraconazole, thiabendazole, ticicophene, thiofanate methyl, thiram, tolclofosmethyl, tolylfluanide, triadimefon, triadimenol, triazoxide, trichlamide triflumisole, triforin, triticonazole, validamycin A, vinclozolin, cineb, tsiram.

 Examples of insecticidal, acaricidal and / or nematicidal substances are 4-bromo-2- (4-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) -1H-pyrrole-3-carbonitrile, N - [(6-chloro- 3-pyridinyl) methyl] -N'-cyano-N-methyl-ethanimidamide and trading products abamectin, acephate, acrinatrin, alanicarb, aldicarb, alfamethrin, amitraz, avermectin, AZ 60541, azadirachtin, azinphos A, azinphos M, azocyclotin bendiocarb, benfuracarb, bensultap, betacilutrin, bifentrin, BRMS, brofenprox, bromfos A, bufencarb, buprofetzin, butocarboxin, butylpyridabene, caduzafos, carbaryl, carbofuran, carbofer otion, carbosulfan, cartap, hloretokarb, chlorethoxyfos, chlorfenvinphos, chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos M, cis-resmethrin, klotsitrin, Clophen-Tesino, cyanophos, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin, tsiper-metrin, cyromazine, deltamethrin, demeton M, demeton S, demeton-S-methyl, diafentiuron, diazinon, dichlorofention, dichlorvos, diclifos, dicrotofos, diethion, diflubenzuron, dimethoate, dimethylvinphos, dioxation, disulfoton, edifenfos, etamefenoferfen, etamefenoferfen, etamefroenfent, etofeferfen, etofeferfen, etofeferfen, etofenoferfen, , fenamiphos, enazakvin, fenbutatin oxide, fenitrothion, fenobucarb, fenothiocarb, fenoxycarb, fenpropathrin, fenpirad, fenpyroximate, fenthion, fenvalerate, fipronil, fluazinam, fluazuron, flucycloxuron, flucythrinate, flufenoxuron, flufenprox, fluvalinate, fonofos, formothion, fosthiazate, fubfenproks, Furathiocarb, HCH, heptenophos, hexaflumuron, hexithiazox, imidacloprid, iprobenfos, isocophos, isofenfos, isoprocarb, isoxathion, ivemectin, lamdacigalotrin, lufenuron, malathion, mecarbam, mervinfos, mesofide metamefide, metrifoside metaphidefide, mesulfide metafidefen, metrifoside metaphidefide, mesulfide metafidefen he, methiocarb, methomil, metolcarb, milbemectin, monocrotophos, moxidectin, iced, NC 184, nitenpyram, omethoate, oxamil, oxydemetone M, oxydeprofos, parathion A, parathion M, permethrin, fentoate, forat, fosimon, fosimon, fosfamone, fosamone, fosamone, fosamone, fosamone, fosalone pirimicarb, pirimiphos M, pirimiphos A, profenofos, promekarb, propaphos, propoxur, prothiofos, protoat, pymetrozine, piraklofos, piradafention, piresmetrin, pyrethrum, pyridaben, pyrimidifen, pyriproxyfen, kvinalfos, salition, sebufos, silafluofen, sulfotep, sulprofos, tebufenozide, tebufenpyrad, tebupirimfos, teflubenz ron, tefluthrin, temephos, terbium terbufos, tetrachlorvinphos, tiafenoks, thiodicarb, tiofanoks, tiometon, tionazin, turingienzin, tralomethrin, triaraten, triazophos, triazuron, trichlorfon, triflumuron, trimetakarb, vamidothion, XMC, ksililkarb, tsetametrin.

 As the herbicidal substances with the above water solubility, anilides can be mentioned, such as, for example, diflufenican and propanyl commercial products, acrylcarboxylic acid, such as dichloropicolinic acid, dicamba and picoloric commercial products, aryloxyalkanoic acids, such as, for example, fluroxypyr and triclopyr, esters of aryloxyphenoxyalkanoic acid, such as, for example, commercial products of diclofop-methyl, phenoxaprop-ethyl, fluazifop-butyl, haloxifop-methyl and quisalofopethyl, azinones, such as for example, commercial products of chloridazone and norflurazone, carbamates, such as, for example, commercial products of chlorprofam, desmedifam, phenmedifam and profam, chloroacetanilides, such as, for example, commercial products of alachlor, acetochlor, butachlor, metazachlor, metolachlor, pretilachlor and propachlor, dinitroanilines such as trading products of oryzaline, pendimethalin and trifluralin, diphenyl ethers, such as trading products of acifluorfen, biphenox, fluoroglycofen, formesafen, halosafen, lactofen and oxyfluorfen, urea such as, for example, a torus Chlorotoluron, Diuron, Fluometuron, Isoproturon, Linuron and Metabenzthiazuron, hydroxylamines, such as, for example, alloxidime, celodime, cycloxydim, sethoxydim and thralcoxidime, imidazolinone, such as imazetapir, imaziritazazabenzam, such as commercial products bromoxynil, dichlorobenyl and ioxynil, oxyacetamides, such as commercial products mefenacet, sulfonylureas, such as commercial products amidosulfuron, bensulfuron-methyl, chlorimuron-ethyl, chlorine sulfuron, cinosulfuron, metsulfuron-methyl, nicosulfuron, primisulfuron, pyrazosulfuron-ethyl, tifensulfuron-methyl, triasulfuron and tribenuron-methyl, thiol carbamates, such as, for example, butylate, cycloate, diallate, EPTC, tarbrocarbate, triallate, triazines, such as, for example, atrazine, cyanazine, simazine, simetrine, terbutrine and terbutylazine, triazinones, such as hexazinone, metamitron and metribuzin, as well as herbicides such as, for example, minotriazole, benfurezate, bentazone, cinmethylin, clomazone, clopyralide, diphenzoquat, dithiopyr, etofumezate, fluorochloridone, glufosinate, glyphosate, isoxaben, pyridate, quinchlorac, quinmerac, sulfosate and tridi.

 The proposed composition may also contain other soluble or insoluble active substances.

 The proposed composition is obtained by dissolving the ingredients in an organic solvent, if necessary, when heated.

 The proposed composition can be used as such, that is, as a concentrate, or in the form of aqueous preparations suitable for use as an oral, parenteral and transdermal drug. In the field of plant protection, they can be used both for spraying leaves, soil and trunk, and for processing seed.

 As a result of the dispersion of the proposed composition in the aqueous phase, depending on the copolymer used and the surfactant used, homogeneous solutions or colloidal dispersions are formed (particle size from 0.01 to 0.4 nm), which are highly stable. These aqueous systems are a working preparation of the proposed composition. The concentration of the active substance in the aqueous working preparation is 0.0001 to 3 weight. %, preferably 0.001 to 2 weight. % To obtain such an aqueous solution or dispersion, the proposed composition is mixed with the required amount of the aqueous phase, if necessary, with stirring or pumping. In this case, the use of special dispersing devices is not required.

 The invention is illustrated by the following examples.

Example 1
1 weight part of nimodipine, 5 weight. parts of a copolymer consisting of 30 weight. % vinylpyrrolidone and 70 weight. % vinyl acetate, and 0.225 weight. parts of sodium dodecyl sulfate are dissolved in 19 weight. parts of 96% ethanol. The resulting concentrate is dispersed in 225 weight. parts of water. In doing so, it is such that a concentrate is rapidly added to the aqueous phase with stirring. Despite the fact that both the active substance and the polymer used are water-insoluble as individual components, a clear solution is formed that does not become cloudy even after a long storage time.

 A measure of the tendency of the active substance to crystallize in an aqueous dispersion is the content of the dissolved active substance, determined after 24 hours of storage of the solution at room temperature. In doing so, proceed as follows. 24 hours after the preparation of the dispersion, a sample is taken, which is filtered through a Millipore brand filter having a pore size of 0.45 μm to remove possible crystals of the active substance. A certain amount of filtrate is dissolved in ethanol and the active substance content is determined by a spectrophotometer. Based on the conversion of the active substance content determined in the framework of the experiment to the theoretical content, the proportion of dissolved and / or colloidal active substance can be established.

 After 24 hours, the content of the filtered active substance is 82% of the applied concentration of 4 mg / ml.

Comparative example
Example 1 is repeated with the difference that to obtain a concentrate containing the active substance, the copolymer is replaced with the same amount of water-soluble polyvinylpyrrolidone (commercial product: Luviskol K 30, BASF, DE). Immediately after dispersing the concentrate, the aqueous phase becomes cloudy due to crystallization of the active substance. After an hour, the crystallized active substance forms a thick bottom sediment, and the supernatant is transparent and almost colorless, which indicates the quantitative crystallization of the active substance. The content of the filtered active substance 24 hours after the preparation of the dispersion is 0%.

Example 2
1 weight part of nimodipine, 4 weight. parts of a copolymer consisting of 20 wt.% vinylpyrrolidone and 80 wt.% vinyl acetate, and 0.225 wt. parts of sodium dodecyl sulfate, dissolved in 15 weight. parts of 96% ethanol. The resulting concentrate is dispersed in 225 weight. parts of water. In doing so, it is such that a concentrate is rapidly added to the aqueous phase with stirring. A colloidal opalescent dispersion is formed, which even after storage for 24 hours does not change the appearance. The content of the filtered active substance after 24 hours is 87% of the applied concentration of 4 mg / ml.

Examples 3 to 8
1 weight part of nimodipine, 5 weight. parts of a copolymer consisting of the weight percentages of vinylpyrrolidone and vinyl acetate shown in table 1, as well as 0.0113 weight. parts of sodium dodecyl sulfate are dissolved in 19 weight. parts of 96% ethanol. According to example 1, the resulting concentrate is dispersed in 225 weight. parts of water. Depending on the ratio of monomers in the used copolymer, homogeneous solutions or colloidal opalescent dispersions are formed, which after 24 hours do not change the appearance, or in which practically quantitative crystallization of the active substance is established. Given in table 1 (see the end of the description) the content of the filtered active substance is determined according to example 1 after standing after 24 hours of storage. It turns out that the inhibitory crystallization effect of the copolymer increases with increasing proportion of vinyl acetate. Pure vinyl acetate, however, is not suitable for obtaining the proposed composition.

Example 9
Fungicide, 1-methyl ester of [2-methyl-1 - [[[[1 - (4-methylphenyl) ethyl] amino] carbonyl] propyl] carboamic acid, monoethanolamine salt of dodecylbenzenesulfonic acid, nonylphenol polyglycol ether with 10 glycol ether copolymers consisting of vinylpyrrolidone and vinyl acetate in a ratio of 60:40 (a commercial product of Luviscol VA 64 from BASF AG, DE) is dissolved in N-methylpyrrolidone, the resulting concentrate is diluted with water to obtain a translucent aqueous colloidal dispersion containing 15% active substance, 5% monoethanol oic dodecylbenzenesulfonate 3% of said simple nonilfenolpoliglikolevogo ester, 5% of said copolymer and 72% methylpyrrolidone. If the Luviskol VA64 copolymer is replaced with polyvinylpyrrolidone according to the above comparative example, then after diluting the concentrate with water, turbid dispersions with coarse particles are obtained, which precipitate within a few minutes.

 The fungicidal activity of the aqueous preparation of this example is determined as follows.

 First, the aqueous preparation is diluted with water to standard concentrations of the active substance. The thus obtained aqueous working preparations are sprayed on young tomato plants until drops form on the plants. For comparison, other tomato plants are treated with aqueous working preparations obtained by diluting with water a wettable powder standard for fungicides containing 2% active substance, 16% nonylphenol glycol ether with 10 glycol ether units, 5% alkylaryl polyglycol ether, 5% highly dispersed amorphous dioxide anhydrous citric acid and 48% crushed silicic acid. These comparative working preparations contain the active substance in the same concentrations as the working preparations obtained from the proposed concentrate.

 After the spray coating has dried, all plants are inoculated with aqueous suspensions of Phytophtera infestans fungal spores. Plants are placed in an incubation chamber at a temperature of 20 ° C and 100% relative humidity. Assessment of the degree of damage to plants depending on the concentration of the active substance is carried out 3 days after inoculation.

 In this experiment, the effect of the proposed drug is already apparent when the concentration of the active substance, which is factor 2 less than the concentration of the active substance in comparative preparations.

 Thus, the proposed composition is not only improved stability, but also improved activity.

 Example 10

 Fungicide, 4-chloro-N, 3'-bis (4-chlorophenyl) -4 ', 5'-dihydro- (1,4'-bi-1H-pyrazole) -1'-carboxamide, monoethanolamine salt of dodecylbenzenesulfonic acid and vinylpyrrolidone copolymer and vinyl acetate in a ratio of 60:40 was dissolved in N-methylpyrrolidone and the resulting concentrate was diluted with water to obtain a translucent aqueous colloidal dispersion resistant to crystallization and sedimentation containing 20% of the active substance, 13% of the dodecylbenzenesulfonic acid monoethanolamine salt, 13% of this copolymer and 54% of N copolymer methyl pyrrolidone. If the copolymer is replaced with polyvinylpyrrolidone according to the above comparative example, then after diluting the concentrate with water, turbid dispersions with coarse particles are obtained, which precipitate within a few minutes.

 The insecticidal activity of the aqueous preparation of this example is determined as follows. First, the aqueous preparation is diluted with water to standard concentrations of the active substance. Cabbage leaves (Brassica oleracea) are immersed in the aqueous preparations thus obtained. For comparison, cabbage leaves are also immersed in aqueous working preparations obtained by diluting with water a standard insecticide preparation containing 19% active substance, 10% propanediol, 20% solvent Enerten 2367, 5% emulsifier PS 29, 0.5% emulsifier Renex 36, 0 , 1% thickener Calzane C and 45.4% demineralized water. These comparative preparations contain the active substance in the same concentrations as the preparations obtained from the proposed concentrate. The effect of the drug against Phaedon cochleariae, Pluteila xylostella, Sporoptera frugiperda and Heliotis viriscens is determined as follows.

 a) Phaedon cochleariae.

 After the above treatment, larvae of a horseradish leaf beetle are placed on the leaves. After 7 days, the degree of killing of the larvae is determined. A measure of the relative biological activity of the proposed drug compared to the standard drug is the concentration ratio at a 50% degree of killing according to the following equation: relative activity = LD 50 (proposed drug) / LD 50 (standard drug). The results of the experiment indicate that the activity of the proposed drug is 8 times higher than the standard.

b) Plutella xylostella
After the above treatment, cabbage moth caterpillars (Plutella xylostella) are placed on the leaves. After 7 days, determine the degree of killing of the tracks according to experience a). Moreover, the relative activity of the proposed drug is 30.

c) Sporoptera frugiperda
After the above treatment, a scoop caterpillar (Sporoptera frugiperda) is placed on the leaves. After 7 days, determine the degree of killing of the tracks according to experience a). In this case, the relative activity of the proposed drug is 20.

d) Heliotis viriscens
After the above treatment, caterpillars that damage the buds of tobacco plants (Heliotis viriscens) are placed on the leaves. After 7 days, determine the degree of killing of the tracks according to experience a). Moreover, the relative activity of the proposed drug is 7.5.

Claims (5)

1. A composition with biological activity, containing a biologically active substance, a vinyl pyrrolidone copolymer and an organic solvent, characterized in that it contains a sparingly soluble substance having a water solubility of less than 0.5 g / 100 ml, and a random copolymer of the formula as a vinyl pyrrolidone copolymer I

where x means the number 0 to 16;
n and m are greater than 1,
with a vinyl ester content of 5 to 90% by weight of the copolymer, the weight ratio between the biologically active substance and the copolymer being from 1: 0.2 to 1: 10, and the composition further comprises at least one surfactant, the proportion of which is the composition is 0.001 to 10 parts by weight per 1 part by weight of biologically active substance.  2. The composition according to p. 1, characterized in that it further comprises a diluent.  3. The composition according to p. 1, characterized in that as a biologically active substance it contains a compound from the group comprising dihydropyridines, azoles, nitromethylene, arylpyrazolines, valinamicarbamates, benzothiophenecarboxamides and / or benzoylurea.  4. An aqueous plant protection product containing a composition with biological activity and water, characterized in that as a composition with biological activity contains a composition according to claim 1.  5. The water tool according to claim 4, characterized in that it further comprises a diluent.

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