HU192907B - Plant protective composition with fungicide activity - Google Patents

Abstract

A fungicidal plant protecting compsn. comprises 3-90 wt.% of a fungicide and 1-90 wt.% of cyclodextrin (alpha, beta or gamma) opt. with usual auxillary agents. - Specifically the ratio of fungicidal active ingredient and cyclodextrin is 90:1-1:5, pref. 2-5:1. The fungicidal active ingredient is pref. benomyl, BCM, metomeclan or phenarimol.

Description

FIELD OF THE INVENTION The present invention relates to a fungicidal plant protection composition comprising cyclodextrin for potentiation. Several publications and patents have recently been published on the use of cyclodextrins in herbicidal formulations [Plant Protection, 19,364 (1983); SzejUi, J.: Cyclodextrins and their Inclusion Complexes, Akadémiai Kiadó, Budapest, 1982.)

Molinate (S-ethyl-N, N-hexamethylene thiocarbonate brown), bentiocarb [S- (4-chlorobenzyl) diethylthiocarbarate] and dichlorophos (2,2-dichlorovinyldimethyl-) phosphate), the volatility of the active ingredient is greatly reduced and thus the efficacy of thousands is maintained over a longer period of time (Mikasa Chemical Industrial Co., Japanese Patent No. 8081806). disclosure document (Kokai); No. 2422316 Public Document of Immigration in the Federal Republic of Germany (1974); Acta Chem. Acad. Sci. Hung. 107, 195 (1981)].

The incorporation of methyl parathion [0,0-dimethyl-O- (4-nitrophenyl) phosphorothioate] and natural pyrethrins and pyrrolides into cyclodextrin can greatly enhance the stability to light and oxygen [Pestic. Sci., II, 134 (1980); No. 3,846,551. U.S. Patent 1974; Nippon Noyalen Gakkoishi, 1, 41 (1976); 2, 41 (1977)]. Diclobenyl (2,6-dichlorobenzonitrile) is easily sublimated, preventing granular products from adhering to one another upon complexation with cyclodextrin. [5 th Int. Cong. Pesticide Chem. (JUPAC), Kyoto (1983).

The complexation of 2-chloroethane-phosphatonic acid with cyclodextrin results in a slow and delayed release of ethylene upon contact with the plant cell, and is therefore more effective than the ethylene released from the very fast-acting active ingredient [Acta Chim. Acad. Sci. Hung. 107: 231 (1981)].

However, on the basis of the literature, it was not expected that cyclodextrin would synergize the efficacy of the fungicides.

SUMMARY OF THE INVENTION It is an object of the present invention to provide fungicidal compositions containing cyclodextrin in which the action of known fungicidal agents is so highly synergistic that a greater effect can be achieved with the same dose or a substantially lower dose of the active ingredient is sufficient to achieve the same fungicidal effect.

The present invention thus provides a fungicidal pesticidal composition comprising from 3 to 90% by weight of a fungicidal active ingredient and from 1 to 90% by weight of cyclodextrin, optionally with other conventional excipients. The ratio of active ingredient to cyclodextrin in the composition may be from 10: 1 to 1: 10, preferably from 2 to 5: 1. As fungicidal active ingredient, the following may be used:

benomyl: 1- (butylcarbamoyl) benzimidazol-2-ylcarbamate;

BCM (carbendazim): 2- (carbomethoxyamino) -benzimidazole;

methomecan: 1- (3,5-dichlorophenyl) -3- (methoxymethyl) pyrrolidine-2,5-dione;

fenarimcl: 2,4'-dichloro-c - (pyrimidin-5-yl) -diphenyl] -methanol.

As the cyclodextrin, β- and / or j- is preferably β-cyclodextrin. The ratio of the above active compounds to the cyclodextrin is sometimes advantageously as follows:

benomyl: cyclodextrin (2-5): 1

BCM: cyclodextrin (2-5): 1 metomeclane: cyclodextrin (1-10): 1 fenarimol: cyclodextrin (1-10): (10-1)

Treatment procedure with boron application 0.5 to 6 kg / ba, preferably 1.2 to 1.6 kg / ha of pesticide is applied to the surface to be treated.

The synergism underlying the present invention may be caused by the following two factors, or the result thereof, one being the fungistatic effect of cyclodextrins and the solubility enhancing effect of cyclodextrins.

The fungistatic action of cyclodextrins, which has not yet been reported in the literature, is illustrated in the following experiment.

0.1-0.2-0.5-1.0-2.0-5.0-10.0-20.0-100.0-200.0-400.0-800.0-1200 were prepared. , 0-1500.0-2000.0-3000.0 μ / ml beta-cyclodextrin agar medium in a Pelri dish. Surface cultures of 3 test fungi were excised into mycelial discs and placed on agar medium in Petri-Ciese. After incubation in a thermostat, the increase in colonial diameter relative to the control culture was assessed, as well as colonial morphology and diffusion of fungal-produced dye into the medium.

Table I

Investigation of the fungistatic effect of beta-cyclodextrin

Concentrations Inhibition% (pg / ml) ------, ..., - ι ----- Mi crorganisms

Rhizoctonia solani

Sclerotínia sclerotiorum

Alternaria tenuis

3000 19 16 14 1500 17 14 12 400 6 12 10 200 3 12 7

The activity of beta-cyclodextrin in the dose range of 0.1 to 20 pg / ml is of a qualitative nature. The fungistatic effect of cyclodextrin is manifested in colonizing morphology, structure, color, and amount of dye diffused into the medium. At higher concentrations, the effect of cyclodextrin has already produced quantitative differences; the reduction in the colonial diameter was measurable and the amount of biomass produced was appreciably reduced. (Table I) In the study of surface cultures, it was observed that β-cyclodextrin inhibited the formation of proliferation formulations. The essence of the solubility enhancement effect of cyclodextrins by inclusion complex formation is that the molecule dispersed cyclodextrin active ingredient is also present in the aqueous solution along with the molecule dispersant, i.e. the actually dissolved active substance and the micelle, microcrystalline, microdroplet consisting of several or many molecules. Since this system is characterized a dynamic unusually (10 ^-8 sec. 'Standing within ¹⁾ balance, zárvénykomplexbe closed agent behaves the same in terms of absorption, as ^a free drug solution.

This means that the concentration of molecularly dispersed drug molecules that are directly absorbable can be significantly increased with cyclodextrins, ^which accelerates the rate of absorption, increases the rate of absorption, i.e., allows a reduction in the amount of drug used to achieve the same effect. The solubility effect of cyclodextrin on the active ingredient is exemplified by the example of benomyl. Benomyl is a systemic fungicide (1-butylcarbamoylbenzimidazol-2-ylmethylcarbamate), slightly soluble in water and rapidly degraded to the less fungicidal methylbenzimidazole carbamate. Benomyl or benomyl + cyclodextrin, shaken in water at 25 ° C. The results are shown in Table III. fBenomyl or benomyl + beta-cyclodextrin (αCD) copper in water at 25 ° C, the sample filtered and the dissolved benomyl in the filtrate determined by UV spectrophotometry.

II. spreadsheet

Increased dissolution of benomyl by beta-cyclodextrin

Testing time (minute) The amount of dissolved bencmil Measured: 1000 pg / ml benomyl Measured: 170 pg benomil + 830 pg / ml aCD pg / ml X pg / ml X 10 2 0.2 7 4.1 20 3 0.3 9 5.3 40 4.5 0.45 10 5.9 80 5 0.5 12 7.0 120 5 0.5 13 7.6

-3192907

Testing time (minute) The amount of dissolved benomyl Measured: 5000 mg / ml benomyl Measured: 850 µg benomil + 4150 µg / ml ^ CD Mg / ml % Mg / ml % 10 3.5 0.07 12 1.4 20 4 0.08 16 1.9 40 6 0.12 17 2.0 80 8 0.16 18 2.1 120 9.5 0.19 19 2.2

Benomil. Fundazole is marketed under the trade name 50 WP, in which 50 wt. In III. The solubility curves for benomyl, benomyl cyclodextrin mixture, Fundazol 50 WP, and Funadazole 50 WP and cyclodextrin mixture are shown in Table II. In each case, 2000 mg / ml was weighed and shaken at 25 ° C. Benomil was 100% active, with benomyl 25% in its mixture with cyclodextrin, benomyl in 50 WP only 50% benomyl and 50.65% benomyl in Fundazol 50 WP + cyclodextrin. As in III. Table 4 shows the formation of a 4-fold increase in the solubility of benomyl.

Cyclodextrin alone, whether considered as the original benomyl or as the solubility of the metered-form Fundazol 50 WP, results in an additional 1.5-2 fold increase in solubility. Given that the amount of benomyl in the cyclodextrin-containing mixtures was significantly lower, while the effective concentration of benomyl in the aqueous solution, which was responsible for the actual biological effect, was significantly higher, it was bloody that this should manifest itself in the biological effect.

III. nutrients

Enhanced Benomyl Dissolution from Fundazole by Theta-Cyclodextrin

Test time is minutes Dissolved benomil (Mg / ml) benomyl benomil <· 0CD Fundazol Fundazol + j »CD 10 2 5 27 40 20 5 8 28 42 40 6 11 29 44 80 7 13 30 46 120 8 13 31 48 160 9 13 32 49

The dissolution of benomyl from various benomyl-containing materials, shaken in water at 25 'C, was 2000 pg / ml of the solid weighed 50, which for benomyl:

benomil 2000 benomil + 3 on CD 350 Fudazole at 50 WP 1000 fundazol For 50 WP + fi CDs 175

Mg / ml

Mg / ml + 1650 m £ 0CD

Mg / ml

Mg / mL + 1650 MgCl2

The assays described below demonstrate the surprisingly high degree of synergism of the action of fungicides with beta-cyclodextrin. High dispersibility stable aqueous suspensions of test substances were mixed in the desired concentration (up to 0.1-200 mg / ml) in agarose medium and poured into Petri dish. Mycelial discs were excised from surface cultures of TBS fungi and placed in a Petri dish containing test substances. After incubation in a thermostat, the increase in colony diameter was evaluated relative to the control culture. The tests were performed in triplicate. The IV. Table 4 shows the effects of the fungicide containing 50% benomyl of the active ingredient Fundazol 50 WP and the beta-cyclodextrin added thereto in an amount of 10%. The results confirm the synergistic role of γ-cyclodextrin, especially in the case of Sotrytis cinerea and Monilia fructigena.

ARC. spreadsheet

Investigation of Fundazole and Fungicidal Activity of Recrystallized Beta-CyclodexTin

Micro-organism EDw (pg / ml relative to active ingredient) Efficiency - Increase (x, fundazol Fundazole + 10% w / w CD Rhizoctonia solani 0.87 0.64 1.3 Sclerotinia sclerotiorum 0:12 0:05 2.4 Fusarium moniliforme 0.88 0:38 2.3 Botrytis cinerea 0:14 0.0125 10.2 Ascochyta piai 0.72 0:25 2.9 Fusarium culmorum 0.77 0:44 1.7 Colletotrichum lini 0.68 0.5 1.3 Monilia fructigena 0:05 0.0125 4.0 The metomeclane contact in water 20 Add cyclodextrin. In Table V, insoluble fungicide [Ί- (3,5- dichloro-phenyl) -3- may be present on metomeclane and 10% beta-cyclo- - (methoxymethyl) pyrrolidine-2,5-dione. for this mixture of dextrin The efficiency of ib fungicide. V spreadsheet Increase in fungicidal activity of metomeclane 10% beta-cyclodextrin by adding EDw (pg / ml, a per active ingredient) Test organisms - - efficiency metomeclan metomeclane + 10% w / w CD enhancement (x) Fusarium moniliforme 12 7 1.7 Alternaria temis 2.9 1.8 1.6 Stemphylium radicinum 5.7 3.9 1.5 Rhizoctonia solani 3.3 2.3 1.4 Colletotrichum lini 25.5 8.9 2.9 Ascochyta pisi 4.6 2.8 1.6 Fusarium culmorum 16.5 7.5 2.2 Alternaria crassa 3.9 2.2 1.8

An in vivo study was conducted on wheat powdery mildew host parasite with a combination of 45 phenarimol [2,4'-dichloro - (- pyrimidin-5-yl) diphenylmethanol] and β-cyclodextrin. The assay was carried out in three replicates, in a phytotron, under the usual experimental system and under ambient conditions (20 ° C, 50 90% humidity, 9000 lux luminous intensity), with an average of 160 plants of 5-6 cm in 8 cm diameter pots. ml of an aqueous suspension of test substance. The results are shown in Table VI. in Table. Gait activity was calculated using the Infection Index using the Hinfner-Papp formula.

VI. spreadsheet

In Vivo Investigation of Fenarimol + Beta-Cyclodextrin in Host-Wheat Dwarf Tuber

Concentrations of pg / ml galaxy activity (%, Fenarimol

Fenarimol + UUC (1: 5 ratio)

2.5

100.0

99.4

87.2

100.0

100.0

98.2

-510

Concentrations in pg / ml inhibitory activity (%) Fenarimol Fenarimol + flCD (1: 5 ratio) 1:25 73.5 83.2 0625 29.4 42.3

VII. Table 21.5 weight percent with the delta-cyclodextrin digs BCM attempted pharmacological active ingredient Kolfugo 21.5 FW (Manufacturer: _erm ényeit described 10 formulas.

CHINOIN) (aqueous suspension)

VH. spreadsheet

Inhibition activity of Kolfugo- # CD formulations in Rhizoctonia solani

Concentrations (pg / ml)

Inhibitory activity X

K-21.5 FW

K-21.5 FW + 0.5 wtX £ CD

5.0 100.0 100.0 4.5 100.0 100.0 4.0 76.9 87.2 3.5 70.5 85.9 3.0 59.0 75.6 2.5 57.7 64.1 2.0 55.8 62.8

K = Kolfug

In a further series of experiments, we investigated whether well-known linear dextrins produced by thermal or enzymatic or acidic degradation of starch have similar effects to cyclodextrins. The experiments performed have clearly demonstrated that the fungicide-synergistic activity described is exclusively cyclodextrin, which can significantly reduce the doses of the known and widely used active ingredients to achieve unchanged or enhanced activity, resulting in significant cost savings of active ingredients. it can also be environmentally friendly.

Example 1

Benomil spray containing active ingredient

Benomyl Sprayers is currently marketed as a 50X wettable powder containing 50X active ingredient under the trade name Fundazol 50 WP. The product having the same effect but with less active ingredient is prepared as follows.

60 kg of benomyl pre-micronized in a jet mill and 15 kg of crystalline beta-cyclodextrin also pre-micronized in a jet mill (with a moisture content of 13%) are mixed with 40 kg of calcium carbonate, 5 kg of target preheated). After homogenization, the material is dried and then micronized again to separate the sticky particles and pack the product.

Example 2

The procedure is the same as described in Example 1, so that the components must be micronized, homogenized, dried and re-micronized. The composition is as follows: benomyl (based on 100% active ingredient) 40 kg calcium carbonate 40 kg, Tensiofix BCa 2.5 kg, Totamin 5 kg and beta-cyclodextrin 12.5 kg.

Example 3

Benomil is an active ingredient in a café

The procedure is the same as described in Example 1, the composition of which is as follows: benomil 35 kg, Diotylan 1 kg, Yvid 27 1 kg, Tyloee N 20 1 kg, Aerosil 300 0.5 kg, Safranin B extra 2 kg, spray dried crude conversion cyclodextrin mixture (content of beta-cyclodextrin about 48%, content of alpha- and gamma-cyclodextrin about 2%, content of partially degraded starch about 50%) 38 kg, calcium carbonate 21.5 kg.

-612

Example 4

BCM (2- (Carbomethoxyamino) -benzimidazole) -containing agent The BCM is dissolved by heating with hydrochloric acid, then neutralized with an emulsion of a mixture of ammonium hydroxide, paraffin oil, and beta cyclodextrin, and stabilized in a known manner with surfactants.

The composition of the composition is as follows:

BCM 15% Paraffin Oil 19.8% Bile Cyclodextrin 5% Ethylene Glycol 5.6% Ammonium Chloride (Approximately 10% formed during the neutralization of the saline solution)

Various surfactants: Bmulsogen M 0.24% Atlox 4868 B 1.6% Triton X 45 1.9% Tensiofix L 051 0.2% Tensiofix 821 0.2%

it is 100% water.

5-6. example

The procedure is the same as described in Example 1, the composition of which is as follows:

5.6.

benomyl 60 kg 75 kg was diethyl 1 kg 1 kg Year 27 1 kg 1 kg In silent N 20 1 kg - 1 kg Aerosil 300 0.5 kg - 0.5 kg Safranin B extra 2kg 2 kg CD was 20 kg 10 kg CaCO ₃ 14.5 kg - 9.5 kg

Example 7

The following composition is prepared:

benomil 10 kg

Diotylene 5 kg

Na-lignin sulfone 5 kg

CD mix 80 kg

Chemical composition and manufacturer of excipients used in the examples:

Genspol PGM = Na-alkyl ether sulfate (manufactured by Hoechst) Tensiofix BCj - Ca-C 1-4 alkylbenzene sulfonate and C 1-4 alkyl alkyl phenol- 5 Totamin = poly (ethylene glycol) poly (propylene glycol) ether (manufactured by: Tenzin) tetraethyl-rhodamyl (manufactured by: United Chemicals) 10 Diotylan = Na-Dioctylsulfosuccinate (manufactured by Am. Cyanamid) Yearly = 27 alkyl polyglycol ether-Na (manufactured by United Chemicals) 15 Tyloeie N 20 = Na- (arm boxi-me til) cellulose (manufactured by Hoechst) Aerosil "300" = synthetic silica (manufactured by Degussa) Safranin B extra = colorant (manufacturer: 20 Emulsogen M = Merck) fatty alcohol polyglycol ether (manufactured by Hoechst) Atlox 48683 = complex of polyoxyalkylene ester and urea (factory 25 Triton X 45 = lake: ICI) octylphenoxy-polyethoxyethanol (manufactured by Rohm A Haas) Tensiofix L 051 = oil oil emulsion (antifoam) (manufactured by Tenzia) 30 Tensiofix 821 = polysaccharide (manufactured by Tenzia) CaCO3 (precipitate) (manufactured by John A E. Sturge Ltd)

Claims (2)

PATENT CLAIMS CLAIMS 1. A fungicidal plant protection composition, characterized in that it is a fungicide 1-4 butylcarbamoylbenziraidazol-2-ylmethylcarbamate or 2- (carbomethoxyamino) benzimidazole or 1- (3,5-dichlorophenyl) -3- (methoxymethyl) pyrrolidine-2,5-dione; 45 2,4'-dichloro-α- (pyrimidin-5-yl) -diphenylmethanol, 1-90% by weight of cyclodextrin and optionally 100% by weight of other commonly used excipients. (s) Preferably condensation products of ethylene oxide with fatty alcohols, alkyl phenols, Ca-alkyl arylsulfonotol, alkylaryl polyether alcohol; containing fillers and / or diluents such as ethylene glycol, calcium carbonate, Weight ratio of 55 fungicides to cyclodextrin (10-1): (1-10). 2. A composition according to claim 1, wherein the cyclodextrin is (1) -cyclohextrin.