JP3237077B2 - Aqueous suspension formulation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an aqueous suspension preparation, and more particularly, to penta-4-enyl-N-furfuryl-N-imidazol-1-ylcarbonyl-DL-homoalaninate (hereinafter referred to as "compound") as an active ingredient. [A])).

[0002]

Technical background of the invention The above compound [A] has an excellent seed disinfecting effect against rice scab and seedling disease, and can be used alone or in combination with other agents to make wettable powders, emulsions, flowables (water suspensions). Widely used in dosage forms such as

An aqueous suspension prepared by suspending this compound [A] in water in the presence of a suitable surfactant is, for example, 40
When stored under severe conditions of 60 ° C. for 60 days (this is a condition corresponding to storage at room temperature for 2 years), the compound [A] is decomposed as much as 40 to 50%. was there. In addition, the decomposition of the compound [A] may be further promoted by a compound (fungicide) such as thiuram: bis (dimethylthiocarbamoyl) disulfide used in combination.

[0004] In order to solve such problems, intensive studies have been conducted. As a result, in an aqueous suspension formulation containing this compound [A] and a specific compound, the compound [A] does not decompose.
The inventors have found that they have excellent long-term storage stability, and have completed the present invention.

Japanese Unexamined Patent Publication (Kokai) No. 2-188502 discloses an aqueous suspension biocide composition comprising water-insoluble biocide particles having a melting point of 15 to 18 ° C. suspended in water. One or more selected from terephthalic acid esters, trimellitic acid esters, pyromellitic acid esters, naphthoic acid esters, higher fatty acid esters, and adipic acid esters in a weight ratio of 0.1 to 2. An aqueous suspension biocide composition containing 0 proportion is disclosed, which states that no crystallization occurs during storage.

However, this publication does not disclose the above compound [A] as a biocide, and therefore describes how to prevent the degradation of compound [A] in an aqueous suspension formulation. There is no teaching.

[0007]

SUMMARY OF THE INVENTION The object of the present invention is to solve the problems associated with the prior art as described above, and it is excellent in long-term storage stability, and the compound [A] exhibits a long-term storage even after long-term storage. It is an object of the present invention to provide an aqueous suspension formulation containing the compound [A], which does not decompose into water.

[0008]

SUMMARY OF THE INVENTION The aqueous suspension preparation according to the present invention comprises, as an active ingredient (medicinal ingredient), a penta-4- represented by the following formula [A].
It is characterized by containing enyl-N-furfuryl-N-imidazol-1-ylcarbonyl-DL-homoalaninate (compound [A]) and a dibasic acid ester as a stabilizer for the compound [A].

[0009]

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In a preferred embodiment of the present invention, the dibasic acid ester is adipic acid ester, phthalic acid ester, sebacic acid ester, malonic acid ester, glutaric acid ester, maleic acid ester, succinic acid ester, fumaric acid ester and Desirably, one or two or more esters selected from oxalic esters are used.

The aqueous suspension preparation according to the present invention comprises a compound [A] having an action as an active ingredient (such as a bactericidal active ingredient) as described above, and a dibasic acid ester as a stabilizer of the compound [A]. The compound [A] is inhibited from decomposing even when stored under severe conditions for a long period of time (eg, stored at a high temperature of 40 ° C. for 60 days), and has excellent long-term storage stability. ing.

[0012]

DETAILED DESCRIPTION OF THE INVENTION Hereinafter, the aqueous suspension preparation according to the present invention will be described specifically. Compound [A] The aqueous suspension formulation according to the present invention contains penta-4-enyl-N-furfuryl- represented by the following formula [A] as an active ingredient.
It contains N-imidazol-1-ylcarbonyl-DL-homoalaninate and a dibasic acid ester as a stabilizer for the compound [A].

[0013]

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The compound [A] has a function as a bactericidal active ingredient and has a solubility in water of 443 ppm (25 ppm).
° C), and is a viscous yellow-brown liquid at room temperature. In the aqueous suspension preparation according to the present invention, the content of the compound [A] is not particularly limited, but is usually 1 to 5
It is desirably contained in the aqueous suspension in an amount of 0% by weight, preferably 5 to 30% by weight.

[ Dibasic acid ester ] The dibasic acid ester contained in the aqueous suspension preparation of the present invention prevents the decomposition of the compound [A] and enhances the storage stability of the compound [A]. It seems to be.

The dibasic acid ester may be a monoester or a diester, but is preferably a diester. When the dibasic acid ester is a diester, one dibasic acid is used. May have a structure formed by bonding two alcohols, and a structure formed by bonding two kinds of alcohols (eg, decyl alcohol and isodecyl alcohol) to a dibasic acid. May be.

The alcohol used for forming such a dibasic acid ester includes aromatic alcohols,
Alicyclic alcohols, aliphatic alcohols and the like can be mentioned. As the aromatic alcohol, benzyl alcohol,
Cinnamyl alcohol and the like; alicyclic alcohols such as cyclopentanol and cyclohexanol; and aliphatic alcohols such as methyl alcohol, ethyl alcohol, butyl alcohol and n-
Monovalent linear alcohols such as hexyl alcohol, octyl alcohol, and decyl alcohol; monovalent branched alcohols such as isopropyl alcohol, isobutyl alcohol, t-butyl alcohol, isononyl alcohol, isodecyl alcohol, and isooctyl alcohol; And dihydric alcohols such as butanediol (butyl glycol). Among these, aliphatic alcohols are preferable, and among them, linear or branched alcohols having 1 to 18 carbon atoms are particularly preferable.

The dibasic acid used for forming such a dibasic acid ester includes adipic acid, phthalic acid, sebacic acid, malonic acid, glutaric acid, maleic acid, succinic acid, fumaric acid, and oxalic acid. Acids and the like.

More specifically, the above-mentioned dibasic acid esters include, for example, dimethyl adipate, diethyl adipate, diisopropyl adipate, dibutyl adipate, diisobutyl adipate, di-n-hexyl adipate, adipic acid Dioctyl, diisononyl adipate, didecyl adipate, diisodecyl adipate, decyl isooctyl adipate, diisooctyl adipate, dibutyl diglycol adipate, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, diheptyl phthalate, dioctyl phthalate, Di-n-octyl phthalate, diisononyl phthalate, octyldecyl phthalate,
Diisodecyl phthalate, butyl benzyl phthalate, dibutyl sebacate, dioctyl sebacate, dimethyl malonate, diethyl malonate, di-t-butyl malonate, dibenzyl malonate, dimethyl glutarate, diethyl glutarate, dioctyl glutarate, maleic Dimethyl acrylate, diethyl maleate, dibutyl maleate, dioctyl maleate, dimethyl succinate, diethyl succinate, dibutyl succinate, dioctyl succinate, dimethyl fumarate, diethyl fumarate, dibutyl fumarate, dioctyl fumarate, dimethyl oxalate , Diethyl oxalate, dibutyl oxalate and the like.

Of these, dimethyl adipate,
Diethyl adipate, diisopropyl adipate, dibutyl adipate, isobutyl adipate, diadipate
-n-hexyl, dioctyl adipate, diisodecyl adipate, decyl isooctyl adipate, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, di-n-octyl phthalate, dioctyldecyl phthalate, dibutyl sebacate, sebacic acid Dioctyl, dimethyl malonate, diethyl malonate, di-t-butyl malonate, dimethyl glutarate, diethyl glutarate, dioctyl glutarate, dimethyl maleate, diethyl maleate, dibutyl maleate, dioctyl maleate, dimethyl succinate, Diethyl succinate, dibutyl succinate, dioctyl succinate, dimethyl fumarate, diethyl fumarate, dibutyl fumarate, dioctyl fumarate, dimethyl oxalate, diethyl oxalate, and dibutyl oxalate are preferably used.

In the present invention, one or more of these dibasic acid esters may be used in combination. In addition, such a dibasic acid ester may be formed by an esterification reaction between the dibasic acid and the alcohol as described above, or may be formed by a transesterification reaction, and the production method is not particularly limited. .

These dibasic acid esters are safe, have no harm to useful crops, have little toxicity and side effects on humans and livestock, and can be used safely. This dibasic acid ester has a function as a stabilizer for the compound [A], and is usually contained in the aqueous suspension in an amount of 0.1 to 40% by weight, preferably 1 to 30% by weight. Good to be. In the present invention, the type of the dibasic acid ester (stabilizer) used, the content of the compound [A],
The content of the dibasic acid ester in the aqueous suspension preparation can be appropriately increased or decreased within the above range according to the difference in the environmental conditions in which the aqueous suspension preparation is stored and the like.

[ Production of Aqueous Suspension Formulation ] The aqueous suspension formulation according to the present invention as described above is prepared by, for example, mixing the compound [A], a dibasic acid ester, and a surfactant used as necessary, Other auxiliary agents, such as thickeners, antifreezing agents, antifoaming agents, antioxidants, antioxidants, UV inhibitors and the like are added to water and stirred, and the above components are dispersed in water. Can be

The surfactant is not particularly limited as long as it has the function of emulsifying and dispersing the above compound [A] in water, and includes the following conventionally known nonionic surfactants, anionic surfactants, and cations. Surfactants, amphoteric surfactants and the like can be mentioned, and among them, nonionic surfactants are preferably used.

Examples of the nonionic surfactant include polyoxyethylene alkyl aryl ether (eg, polyoxyethylene nonyl phenyl ether), polyoxyalkylene aryl phenyl ether, polyoxyethylene styryl phenyl ether, polyoxyethylene alkyl ester, Polyoxyethylene sorbitan alkylate, polyoxyalkylene glycol, polyoxyethylene phenyl ether polymer and the like. Specific examples of the anionic surfactant include, for example, lignin sulfonate, alkylaryl sulfonate, dialkyl Sulfosuccinate, polyoxyethylene alkyl aryl phosphate, polyoxyethylene alkyl aryl ether sulfate, alkyl naphthalene sulfonate, Such as polyoxyethylene styryl phenyl ether sulfate and the like.

Specific examples of the cationic surfactant and the amphoteric surfactant include alkylamines, quaternary ammonium salts, alkylbetaines, and amine oxides.

In the present invention, these surfactants can be used alone or in combination of two or more in such an amount that the content of these surfactants in the obtained aqueous suspension preparation is 1 to 30% by weight. The surfactant that can be used in the present invention is not limited to the above examples.

Specific examples of the thickener include, for example, xanthan gum, guar gum, tragacanth gum, gum arabic, casein, dextrin, carboxymethyl cellulose, sodium carboxymethyl starch, sodium alginate, hydroxyethyl cellulose, carboxyethyl cellulose, methyl cellulose, hydroxy cellulose Examples include propylcellulose, hydroxyethylcellulose, polyvinyl alcohol, polyacrylic acid and its derivatives, colloidal hydrous aluminum silicate, colloidal hydrous magnesium silicate, and colloidal hydrous aluminum aluminum silicate. In the present invention,
One or a combination of two or more of these thickeners can be used in an amount such that the content of these thickeners in the obtained aqueous suspension preparation is 0.05 to 10% by weight. In addition, the thickener which can be used in the present invention is not limited to the above examples.

Specific examples of the antifreezing agent include ethylene glycol, propylene glycol, glycerin and the like. As the antifoaming agent, silicon-based or fatty acid-based ones can be used. Examples of the antibacterial agent (antifungal / preservative preservative) include, for example, sorbic acid, potassium sorbate, p-chloro-metaxylenol, and p-butyl benzoate. it can. The auxiliary agent usable in the present invention is not limited to the above examples.

In preparing the aqueous suspension preparation according to the present invention, "another active ingredient" may be used in combination with the compound [A]. As other active ingredients, specifically,
For example, fungicides such as kasugamycin, TPN, hydroxyisoxazole, benomyl, thiuranium, basic copper sulfate, basic copper chloride, oxine copper, cupric hydroxide and the like can be mentioned. In the present invention, these active ingredients may be used alone or in combination of two or more. For example, the aqueous suspension formulation according to the present invention containing the thiuram and the compound [A] as active ingredients has excellent stability even when stored under severe conditions for a long period of time. ]
Is hardly decomposed. Other active ingredients that can be used in the present invention are not limited to the above examples.

In the present invention, the amount of such “other active ingredients” is not particularly limited, but the content of “other active ingredients” in the obtained aqueous suspension preparation is usually
The amount may be 1 to 50% by weight, preferably 5 to 30% by weight. When the compound [A] and the "other active ingredient" are used in combination, it is preferable to use the compound [A] in an amount such that the total amount of these active ingredients is 10 to 50% by weight.

The names of the above-mentioned active ingredients and the like are the common names described in "Agrochemical Handbook 1992 Edition" (published by the Japan Plant Protection Association).

[0033]

The aqueous suspension preparation according to the present invention includes, for example,
Even when stored at room temperature for 2 years, the compound [A], which is a bactericidal active ingredient in the preparation, has a decomposition rate of 6% or less, and has excellent storage stability.

[0034]

EXAMPLES Next, the aqueous suspension preparation of the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. For example, the content of the compound [A], the type and amount of stabilizer added, the type and amount of various adjuvants, the method of producing an aqueous suspension, and the like can be appropriately changed and carried out.

In the following Examples and Comparative Examples, "parts" means "parts by weight".

[0036]

Example 1 A solution (a-1) obtained by stirring 20 parts of the compound [A], 5 parts of diisobutyl adipate, and 5 parts of polyoxyethylene nonylphenyl ether, was previously prepared with 60 parts of water, 5 parts of ethylene glycol and 2 parts. A mixed solution (b-1) obtained by mixing and dissolving 5 parts of an aqueous xanthan gum solution (5 parts) was mixed. Solution (a-1)
During the mixing of the mixed solution (b-1) with the mixed solution (b-1), the mixed solution (b-1) was stirred using a "Three One Motor" (manufactured by Fuji Photo Film Co., Ltd.) at a rotation speed of 700 rpm. After completion of the mixing, the obtained mixed liquid was stirred and mixed at a rotation speed of 5000 rpm for about 20 minutes using a “TK Homomixer” (manufactured by Nippon Tokushu Kika Kogyo Co., Ltd.) to obtain an aqueous suspension of the present invention. A cloudy formulation was obtained.

In place of diisobutyl adipate (Test Example No. 6 in Table 1), the above-mentioned dibasic acid esters (stabilizers) were used in such a manner that one kind and amount of the stabilizers shown in Tables 1 to 3 were used. ) Can be used to obtain the same aqueous suspension formulation as described above.

[0038]

Example 2 8 parts of compound [A], dimethyl phthalate 5
Of a solution (a-2) obtained by stirring 7 parts of polyoxyethylene styryl phenyl ether and 62 parts of water, 5 parts of ethylene glycol and 3 parts of a 2% xanthan gum aqueous solution in advance (b- And 2) were mixed. Solution (a-2)
During the mixing of the mixture (b-2) with the mixture (b-2), the mixture (b-2) was stirred at 700 rpm by a three-one motor. After the mixing is completed, 10 parts of the thiuram substance is added to the obtained mixed solution, and T
The mixture was stirred and mixed with a K homomixer at 5000 rpm for 20 minutes to obtain an aqueous suspension formulation of the present invention.

Incidentally, dimethyl phthalate (Test Example N in Table 1)
o. In place of 12), it is possible to obtain the same aqueous suspension preparation as described above using the other dibasic acid ester (stabilizer) so as to be one of the stabilizers and the amounts shown in Tables 1 to 3. it can.

[0040]

Example 3 A solution prepared by stirring 20 parts of compound [A], 10 parts of dimethyl adipate, 5 parts of dioctyl succinate, and 10 parts of polyoxyethylenestyrylphenyl ether
-3) was previously prepared with 47 parts of water, 5 parts of ethylene glycol, and 2%
Mixed solution obtained by mixing and dissolving 3 parts of xanthan gum aqueous solution
It mixed with (b-3). When mixing the solution (a-3) and the mixed solution (b-3), the mixed solution (b-3) was rotated at a rotational speed of 7 by a three-one motor.
The mixture was stirred at 00 rpm. After the completion of mixing, the obtained mixture was rotated at 5,000 rpm with a TK homomixer.
For about 20 minutes to obtain an aqueous suspension formulation of the present invention.

It should be noted that two kinds of stabilizers (Test Example No. 45) and amounts shown in Table 2 were used instead of dimethyl adipate and dioctyl succinate (Test Example No. 44 in Table 2). Alternatively, an aqueous suspension formulation similar to the above can be obtained using two of the above-mentioned dibasic acid esters (stabilizers).

[0042]

Example 4 Compound [A] 20 parts, dimethyl adipate 1 part, dimethyl succinate 1 part, dimethyl glutarate 3
Part, polyoxyethylene styryl phenyl ether 10
The solution (a-4) obtained by stirring the parts was mixed with a mixed solution (b-4) in which 57 parts of water, 5 parts of ethylene glycol, and 3 parts of a 2% xanthan gum aqueous solution were mixed and dissolved in advance. This solution (a-
At the time of mixing the mixture (4) with the mixture (b-4), the mixture (b-4) was stirred by a three-one motor at a rotation speed of 700 rpm. After completion of the mixing, the obtained mixed liquid was stirred and mixed at 5,000 rpm for about 20 minutes with a TK homomixer to obtain an aqueous suspension preparation of the present invention.

Incidentally, three kinds of dimethyl adipate, dimethyl succinate and dimethyl glutarate (Test Example No.
46, Test Example No. The same aqueous suspension formulation as described above can be obtained by using the above-mentioned dibasic acid ester (stabilizer) in place of (59).

[0044]

Comparative Example 1 An aqueous suspension preparation was obtained in the same manner as in Example 1, except that 5 parts of water was used instead of 5 parts of diisobutyl adipate.

[0045]

Comparative Example 2 An aqueous suspension preparation was obtained in the same manner as in Example 2, except that 5 parts of water was used instead of 5 parts of dimethyl phthalate.

Next, the storage stability of the aqueous suspension preparation of the present invention will be specifically described by test examples.

[0047]

[Test Examples 1 to 59 and Comparative Test Examples 1 to 2] Decomposition prevention effect tests The aqueous suspension preparations shown in Tables 1 to 3 below were prepared according to Examples 1 to 4, and the compounds [A] and (and thiuram) were prepared. Was analyzed in advance by gas gas chromatography.

50 g of each of the aqueous suspensions was put in a glass bottle, sealed and left in a high-temperature container at 40 ° C. for 60 days (corresponding to standing at room temperature for 2 years). Thereafter, the aqueous suspension preparation contained in the glass bottle was taken out of the high-temperature container, and the content of the compound [A] was analyzed by gas gas chromatography to determine the residual ratio (%) with respect to the initial content value.

The results are shown in Tables 1 to 4.

[0050]

[Table 1]

[0051]

[Table 2]

[0052]

[Table 3]

[0053]

[Table 4]

Continuation of the front page (72) Inventor Yuichi Kurosu 965-15 Tomuro, Atsugi-shi, Kanagawa Prefecture Heights Silk 103 (72) Inventor Shinji Yonemura 1-81-11-205 Okada, 8-1-1205, 56-56 Reference Document JP-A-4-202102 (JP, A) JP-A-4-193808 (JP, A) JP-A-4-264010 (JP, A) JP-A-2-188502 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) A01N 43/50 A01N 25/04 102 C07D 405/12

Claims (2)

(57) [Claims] (1) Penta-4-enyl-N-furfuryl-N-imidazol-1-ylcarbonyl-DL-homoalaninate represented by the following formula [A]: Aqueous suspension formulation excellent in storage stability characterized by containing a basic acid ester: 2. The dibasic acid ester is adipic acid ester, phthalic acid ester, sebacic acid ester, malonic acid ester, glutaric acid ester, maleic acid ester,
The aqueous suspension preparation according to claim 1, which is one or more esters selected from succinate, fumarate and oxalate.