JPS624210A - Validamycin preparation - Google Patents

Abstract

PURPOSE:Stabilized validamycin preparation obtained by adding at least one of metallic oxides consisting of titanium dioxide, aluminum oxide, calcium oxide and zirconium oxide to validamycin when validamycin is blended with an acidic, solid preparation. CONSTITUTION:When an acidic, solid preparation is added to validamycin showing a strongly alleviating action on sheath blight, having hardly phyto toxicity to men, beasts and fishes and shellfishes, causing hardly abnormality in germination, growth, yield, etc., when it is used for useful plants even in high concentration, validamycin is blended with 3-300pts.wt., especially 5-150 pts.wt. based on 1pt.wt. validamycin of at least one of metallic oxides such as titanium dioxide, aluminum oxide, calcium oxide and zirconium oxide, to give stabilized validamycin preparation.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a stabilized validamycin combination formulation.

(Prior Art) Conventionally, organic arsenic agents have been commonly used to treat plant sheath blight, and pentachloronitrobenzene agents have been widely used to treat damping off and white silk, but these do not necessarily affect humans or animals.

It could not be said to be safe for seafood or crops. On the other hand, although validamycin exhibits a strong rheotrophic effect, it is virtually harmless to humans, livestock, and seafood, and even when used at high concentrations on useful plants, it causes almost no abnormalities in germination, growth, yield, etc. It didn't bother me. In addition, validamycin is used not only for sheath blight, but also for small grain sclerotia of rice, flower regrowth, and damping off of seedlings.

It was also highly effective against plant diseases such as white silk disease.

Although validamycin shows almost no antibacterial activity using conventional antibacterial test methods, it is unique in that it exhibits a remarkable disease control effect when sprayed on plants or treated with soil.

However, validamycin has the disadvantage that it not only decomposes due to moisture absorption, light, temperature rise, etc., but also rapidly decomposes in the coexistence of acids, especially strong acids.

Decomposition due to moisture absorption, light, temperature rise, etc. can be prevented to a considerable extent by using moisture-proof bags, light-shielding containers, etc., or by adding stabilizers, decomposition inhibitors, antioxidants, etc. However, acids, especially strong acids, No method has yet been found to prevent decomposition in the coexistence of

(Problems to be Solved by the Invention) In general, agricultural pesticide formulations include not only those that are expected to have a single medicinal effect from a single agricultural chemical active substance, but also those that are expected to have a single medicinal effect by combining two or more types of agricultural chemical active substances. There are mixed preparations that are expected to have a wider range of excellent medicinal effects than the case of a single active substance, or that are aimed at labor-saving simultaneous control.

Pesticide formulations generally require a long period of time from manufacture to use, during which time the agrochemical active substance may undergo chemical reactions with the various carriers and auxiliary ingredients incorporated into the formulation, or mixed formulations may In some cases, active substances can undergo chemical reactions with each other and decompose, resulting in no longer showing biological activity or even causing drug damage.

As mentioned in the prior art section, although validamycin is significantly degraded in the coexistence of acids, especially strong acids, there are many attempts to manufacture preparations that incorporate validamycin into acidic solid preparations. . As detailed in Examples 1 to 4 in the section on means for solving the problem, for example, 5-methyl-1,2,4-)riazolo[3,4-b cobenzothiazole (hereinafter abbreviated as TC) ) and organophosphorus insecticides (e.g. 0.0-dimethyl thiophosphate 0-
(3-methyl-4-nitrophenyl, hereinafter abbreviated as MEP), and for stabilizing mixed preparations with bis(thiocarbamic acid) S,S'-[2-(dimethylamino)
In order to stabilize trimethylene glycol (hereinafter abbreviated as cartap), a method of blending strong acids such as oxalic acid and benzenesulfonic acid has been adopted.
If you try to add validamycin to O-MEP mixed preparation or Cartap preparation, TC-MEP or CA
The acid used to stabilize rtap degrades validamycin. Therefore, it has been desired to establish a method for stabilizing agrochemical formulations containing validamycin in acidic solid formulations.

The present inventors have discovered that when a specific metal oxide is added to validamycin in an acidic solid preparation, the decomposition of validamycin can be suppressed very well, and after further study, the present invention was completed.

(Means for Solving the Problems) The present invention incorporates at least one specific metal oxide, namely, titanium dioxide, aluminum oxide, calcium oxide, and zirconium oxide, when formulating validamycin into an acidic solid preparation. The present invention relates to a stabilized validamycin mixed preparation characterized by the following.

Validamycin in the present invention is, for example, Streptomyces hygroscopicus var limoneus (St.
reptomyces hygroscopicus
War.

1 imoneus), and its production method, biological properties, and physicochemical properties have already been clarified [for example, Japanese Patent Publication No. 46-28831. 46-37750, etc.], the main component of which is validamycin A. Validamycin A
Validamycin B-F' is known as a trace component other than the above. In the present invention, purified validamycin A may be used as validamycin, or any mixture of validamycin A to F may be used. Further, validamycin may be used as its free base in the form of a concentrate or purified product, or as an inorganic acid/organic acid salt or a metal salt.

The metal oxide in the present invention is at least one of titanium dioxide, aluminum oxide, calcium oxide, and zirconium oxide. That is, one type of these metal oxides may be used, or two or more types may be mixed. The amount of the metal oxide added is not particularly limited, but it is particularly effective to use 3 to 300 parts by weight, preferably 5 to 150 parts by weight, of the metal oxide per 1 part by weight of validamycin.

As stated in the previous section, the technology of the present invention relates to validamycin mixed preparations. That is, the acidic solid preparation in the present invention is a solid preparation containing an acid, particularly a strong acid, and an agriculturally active substance other than validamycin. The formulation of the present invention is a mixed formulation containing this acidic solid TI agent and validamycin. In addition to the acid and agricultural active substances other than validamycin, the above-mentioned acidic solid preparations are usually further mixed with various carriers and auxiliary ingredients to form solid dosage forms such as powders and eiwako. Here, various surfactants (for example, lignin sulfonate, alkylbenzene sulfonate, polyoxyethylene alkyl ether, alkylnaphthalene sulfonate, etc.) are used as carriers or auxiliary components.
Dispersants (e.g. ethylene glycol, glycerin, etc.), flow aids (e.g. white carbon, etc.), fixing agents, adsorbents, antioxidants (e.g. dibutylhydroxytoluene, 4°4-thiobis-6-tert-butyl-
3-methylphenol, etc.), preservatives (e.g. sorbic acid, potassium sorbate, etc.), synergists, wetting agents, stabilizers, solvents, excipients, diluents, suspending agents, spreading agents, penetrating agents, Examples include mucilage agents. The above acids include hydrochloric acid, sulfuric acid,
Strong inorganic acids such as phosphoric acid and strong organic acids such as formic acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, oxalic acid, cyanoacetic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and paratoluenesulfonic acid Oxalic acid and benzenesulfonic acid are frequently used. Pesticide active substances other than validamycin include organic sulfur,
Organic phosphorus and organic arsenic.

Disinfectants such as organic chlorine, organic phosphorus, and organic chlorine.

Examples include carbamate-based, pyrethroid-based insecticides and acaricides, and various antibiotics. More specifically, carriers and auxiliary ingredients include, for example, vegetable powders such as soybean flour, tobacco flour, wheat flour, and wood flour, clays (kaolin, bentonite, acid clay, etc.), talcs (talc, waxite powder, etc.). In addition to mineral powders such as silica (diatomaceous earth, mica powder, etc.), solid carriers and auxiliary ingredients such as calcium carbonate, sulfur powder, and activated carbon are often used. Some examples of the above pesticide active substances include: Organic sulfur fungicides: ethylene bis(dithiocarbamic acid) zinc, ethylene bis(dithiocarbamic acid) manganese, ethylene bis(dithiocarbamic acid) ammonium, bis(dimethyldithiocarbamic acid) ethylene Organic phosphorus fungicides such as dizinc bis(dithiocarbamate)
...organic arsenic fungicides such as S-benzyl 01O-diisopropyl thiophosphate, S-diphenyl 〇-ethyl dithiophosphate...organic base fungicides such as iron methanarsonate, iron ammonium methanarsonate...penta Chlorophenol.

Other fungicides such as tetrachloroisophthalonitrile, 4,5,6.7-titrachlorophthalide...TO,N-(trichloromethylthio)-4-cyclohexene-1,2-dicarboximide, phenazine 5-oxide, Organophosphorus fungicides such as methyl l-(butylcarbamoyl)-2-benzimidazolecarbamate...MEP, dithiophosphoric acid S-[
1,2-bis(ethoxycarbonyl)ethyl]0.0-
Dimethyl, 2,2-dichlorovinyl phosphate dimethyl, 2,2,2-)dichloro-1-hydroxyethylphosphonate dimethyl, N-acetylphosphoramidothiolate 01S-dimethyl.

Dimethyl phosphate (E)-1-methyl-2-methylcarbamoylvinyl, dithiophosphate 0.0-dimethyl
Organochlorine insecticides such as S-[α-(ethoxycarbonyl)benzyl], dithiophosphate 0.0-dimethyl 5-(N~methylcarbamoylmethyl)...6.7.8.9.10.10-
Hexachloro-1,5,5a, 6,9. Carbamate insecticides such as '9a-hexahydro-6,9-methano-2,4,3-benzodioxachepine 3-oxide...l-naphthyl methylcarbamate 9-methylcarbamate m-tolyl.

Methylcarbamic acid o-(sec-butylphenyl)
Pyrethroid insecticides such as (hereinafter abbreviated as BPMC)...pyrethrin, allethrin,
Antibiotics such as resmethrin...Other insecticides such as plasticidin S, kasugamycin, polyoxin, oxytetracycline...Acidic solid preparations such as cartap, S-methyl N-(methylcarbamoyloxy)thioacetimidate, etc. are generally listed above. It is produced by mixing the acid, an agriculturally active substance other than validamycin, and optionally a carrier and auxiliary ingredients in a conventional manner, and the dosage form is, for example, a single powder.

The validamycin preparation of the present invention is produced by mixing validamycin and the metal oxide described above with the above acidic solid preparation in a conventional manner. The amount of validamycin added is usually 0.01 to 10 parts by weight, preferably 0.1 to 2 parts by weight, based on 100 parts by weight of the entire formulation. The amount of pesticide active substances other than validamycin in the validamycin mixed preparation is 100 parts by weight of the entire preparation, and in the case of one type, the amount is 0. Ol to 10 parts by weight, preferably 0.05
to 5 parts by weight, and in the case of two or more types, the total is 0.0
1 to 10 parts by weight.

Preferably, the total amount is 0.05 to 5 parts by weight.

Next, an example of a stabilized validamycin mixed preparation produced according to the present invention will be described. Hereinafter, validamycin will be abbreviated as VM.

Example I VM-TC-MEP Mixed Preparation Japanese Patent Publication No. 167502/1987 discloses a technique regarding a stabilized TC-MEP preparation.

That is, by blending oxalic acid or (and) benzenesulfonic acid (hereinafter abbreviated as BSA) to a mixture of TC, a rice blast control agent, and an organic phosphorus compound, such as MEP, as an insecticide, the chemical reaction between the two components can be suppressed. , thereby making it possible to provide a formulation that can exhibit the biological activities of both compounds at once.

On the other hand, VM controls rice sheath blight as mentioned above, but
Since the application times for blast control agents and sheath blight control agents are almost the same, if a mixed formulation of VM-TO-MEP can be manufactured, blast control agents, sheath blight control agents, and insecticides can be combined into one formulation. This can be done simultaneously by spraying. However, when VM is mixed with the above-mentioned stabilized TC-MEP preparation, VM is decomposed by strong acids such as oxalic acid and BSA, and the anti-sheath blight-resistant effect of VM is not fully exhibited. Therefore, as described in the above explanation and Examples 1 to 6, a stable VM-TC-MEP mixed preparation can be obtained by blending VM and a metal oxide into the above TO-MEP preparation. In this case, TC may be a salt.

Example 2 VM-TC-MEP-BPMC mixed preparation This is a preparation in which the VM-TC-MEP mixed preparation of Example 1 was further blended with BPMC, which is a carbamate insecticide. For example, it can be manufactured by the method described in Examples 7 to 9.

Example 3 Mixed preparation of VM-cartap A mixture of VM and cartap, which is highly effective against feeding-damaging pests, is widely used, but it is rapidly decomposed by basic substances. acid, BS
A strong acid such as A may be added. However, when VM is added to a Cartap formulation containing such a strong acid, the VM is decomposed by the acid as described above. Therefore, example to
V in cartap formulations containing acids as described in -12.
Stable V M − by blending M and metal oxide
A cartap mixed formulation can be obtained.

Example 4 VM-Cartap-BPMC mixed preparation This is a preparation in which the VM-cartap mixed preparation of Example 3 is further blended with BPMC. For example, it can be manufactured by the method described in Examples 13-16.

Actions and Effects The validamycin mixed preparation of the present invention does not decompose even if it is an acidic preparation, so it fully exhibits the effect of controlling sheath blight, and with this technology, it can be used against other agricultural chemicals that could not be combined with validamycin in the past. It is now possible to combine it with active substances.

Example I VM O, 3 parts by weight, titanium dioxide 10 parts by weight, TCI
Parts by weight, MEP 3 parts by weight, BSA 1.5 parts by weight, white carbon 2 parts by weight, potassium sorbate 0.
Weigh out the clay so that the total amount is 100 parts by weight, and mix in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 2 VM O, 3 parts by weight, titanium dioxide 2 parts by weight, TCI
Parts by weight, MEP 3 parts by weight, BSA 1.5 parts by weight, white carbon 2 parts by weight, potassium sorbate o,
The clay was weighed so that the total amount was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 3 VM O, 3 parts by weight, titanium dioxide 5 parts by weight, TCI
Parts by weight, MEP 3 parts by weight, BSA 1.5 parts by weight, white carbon 3 parts by weight, potassium sorbate 0.
Weigh out the clay so that the total amount is 100 parts by weight, and mix in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 4 VM O, 3 parts by weight, calcium oxide 10 parts by weight, T
CI parts by weight, MEP 3 parts by weight, BSA 1.5
Clay is weighed out to make a total of 100 parts by weight, including 3 parts by weight of heavy M, 3 parts by weight of white carbon, and 0.1 parts by weight of potassium sorbate, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 5 VM O, 3 parts by weight, aluminum oxide 10 parts by weight, 1
01 parts by weight, MEP 3 parts by weight, BSA 1.5 parts by weight, white carbon 3 parts by weight, potassium sorbate
The clay was weighed out to 0.1 part by weight, and the total amount was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 6 VM O, 3 parts by weight, zirconium oxide 10 parts by weight,
Te 1 part by weight, MEP 3 parts by weight, BSA 1.5
Parts by weight of clay, 3 parts by weight of white carbon, 0.1 parts by weight of potassium sorbate, and the total amount of clay was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 7 VM O, 3 parts by weight, titanium dioxide 10 parts by weight, Te1
Parts by weight, MEP 3 parts by weight, BPMC 2 parts by weight,
BSA, L, 5 parts by weight, white carbon 4 parts by weight,
Potassium sorbate 0.1 parts by weight, total amount 100
Weigh the clay to give parts by weight and mix in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 8 VM O, 3 parts by weight, calcium oxide 10 parts by weight, T
e1 parts by weight, MEP 3 parts by weight, BPMC 2 parts by weight, BSA l.

5 parts by weight of white carbon, 0.61 parts by weight of potassium sorbate, and 0.61 parts by weight of potassium sorbate.

Mix the entire amount again with a flash mixer to obtain a powder.

Example 9 VM O, 3 parts by weight, aluminum oxide 10 parts by weight,
1 part by weight of Te, 3 parts by weight of MEP, 2 parts by weight of BPMC, 1.5 parts by weight of B5A, 4 parts by weight of white carbon, 0.1 part by weight of potassium sorbate, a total of 10 parts by weight
The clay was weighed and mixed in a Raikai machine so that the total weight was 0 parts.

Mix the entire amount again with a flash mixer to obtain a powder.

Example 10 VMO, 3 parts by weight, titanium dioxide 1 (1 part by weight, c
2 parts by weight of artap, 2 parts by weight of oxalic acid, 4 parts by weight of white carbon, 0.1 part by weight of potassium sorbate, the clay was weighed out so that the total amount was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 11 VM O, 3 parts by weight, 10 parts by weight of calcium oxide, c
2 parts by weight of artap, 2 parts by weight of oxalic acid, 4 parts by weight of white carbon, and 0.1 part by weight of potassium sorbate, the clay was weighed so that the total amount was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount with a flash mixer to obtain a powder.

Example 12 VM O, 3 parts by weight, aluminum oxide 10 parts by weight.

2 parts by weight of cartap, 2 parts by weight of oxalic acid, 4 parts by weight of white carbon, 0.1 part by weight of potassium sorbate.

The clay was weighed out so that the total amount was 100 parts by weight and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 13 VM O, 1 part by weight, titanium dioxide 10 parts by weight, ca
rtap 2 parts by weight, BPMC 2 parts by weight, BSA 1
．． 5 parts by weight of white carbon, 0.91 parts by weight of potassium sorbate, and 0.91 parts by weight of potassium sorbate. Mix the entire amount again with a flash mixer to obtain a powder.

Example 14 VM O, 3 parts by weight, calcium oxide 10 parts by weight, c
artap 2 parts by weight, BPMC 2 parts by weight, l3S
A 1.5 parts by weight.

4 parts by weight of white carbon, 0.1 part by weight of potassium sorbate, and 100 parts by weight of clay were weighed and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 15 VM O, 3 parts by weight, aluminum oxide 10 parts by weight.

cartap 2 parts by weight, BPMC 2 parts by weight, BS
1.5 parts by weight of A, 4 parts by weight of white carbon, and 0.1 part by weight of potassium sorbate, the clay was weighed out so that the total amount was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Example 16 VM O, 3 parts by weight, zirconium oxide 10 parts by weight.

cartap 2 parts by weight, BPIAC 2 parts by weight, BS
1.5 parts by weight of A, 4 parts by weight of white carbon, and 0.1 part by weight of potassium sorbate, the clay was weighed out so that the total amount was 100 parts by weight, and mixed in a Raikai machine. Mix the entire amount again with a flash mixer to obtain a powder.

Comparative Example I 3 parts by weight of VM O, 1 part by weight of TC, 3 parts by weight of MEP, 1.5 parts by weight of BSA, 3 parts by weight of white carbon, 0.1 part by weight of potassium sorbate, total amount 100 parts by weight
After weighing the clay to give parts by weight and mixing with a Raikai machine, the entire amount is mixed again with a flash mixer to obtain a powder.

Comparative Example 2 VMo, 3 parts by weight, TCI parts by weight, MEP 3 parts by weight, BPMC 2 parts by weight, BSA 1.5 parts by weight, white carbon 4 parts by weight, potassium sorbate 0.1 parts by weight, total amount 100 parts by weight After weighing the clay and mixing it in a Raikai machine, the entire amount is mixed again in a flash mixer to obtain a powder.

Comparative Example 3 3 parts by weight of VM O, 2 parts by weight of cartap, 2 parts by weight of oxalic acid, 4 parts by weight of white carbon, 0.1 part by weight of potassium sorbate, and clay was weighed so that the total amount was 100 parts by weight. After mixing with a shraikai machine, the entire amount is mixed again with a flash mixer to obtain a powder.

Comparative Example 4 VM O, 3 parts by weight, cartap 2 parts by weight, B
2 parts by weight of PMC, 1.5 parts by weight of BSA, 4 parts by weight of white carbon.

The clay was weighed so that 0.1 part by weight of potassium sorbate and the gold balls were mixed together in a Raikai machine, and then the entire amount was mixed again in a flash mixer to obtain a powder.

Test Examples 2 (1 g) of each of the mixed preparations obtained in Examples 1 to 7, 10, and 13 and Comparative Examples 1 to 4 were placed in a sample container, sealed tightly, and stored at 40°C for 30 days. was taken out and the content of VM was measured by high performance liquid chromatography.The VM decomposition rate (%) was calculated from the following formula.

The test results are shown in the table below.

Claims (1)

[Claims] A stabilized validamycin preparation comprising at least one of titanium dioxide, aluminum oxide, calcium oxide, and zirconium oxide when blending validamycin into an acidic solid preparation.