JPS6233103A - Stable agricultural chemical composition - Google Patents

Abstract

PURPOSE:A stable agricultural chemical composition, obtained by presence of a small amount of cyclodextrin in an unstable agricultural chemical component compound and capable of suppressing decomposition reaction. CONSTITUTION:A stabilized agricultural chemical composition obtained by the presence of cyclodextrin, preferably beta-cyclodextrin at <=0.5, preferably <=0.1mol ratio based on an unstable agricultural chemical component compound (A) in an agricultural chemical formulation containing the unstable agricultural chemical component compound (A). Examples of the compound (A) include oxime carbamate based compounds, e.g. S-methyl-N-[(methylcarbamoyl) oxy]thioacetimidate, organic phosphoric acid ester based compound, or combination thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the stabilization of agrochemical compositions, and more specifically, to the stabilization of agrochemical compositions, and more particularly, to the stabilization of agrochemical compositions, a small amount of cyclodextrin is allowed to coexist in agrochemical formulations containing one or more unstable active pharmaceutical ingredients. The present invention relates to agrochemical compositions stabilized by the present invention.

In recent years, environmental pollution caused by pesticides has become a problem, and DDT.

B)10. The use of pesticide active ingredient compounds that are themselves stable, such as dorin agents, is regulated, and instead they are unstable,
Active ingredient compounds with less accumulation and environmental pollution are emerging. The technology for stably retaining these easily degradable active ingredient compounds in formulations has become very important.

When an unstable active ingredient breaks down in a drug product, it not only reduces the biological effect, but also significantly deteriorates the physical properties of the drug product, resulting in a loss of commercial value, or often promoting phytotoxicity to crops. Because of this, many studies have been made to stabilize it.

In the past, various methods have been proposed for stabilization, such as selecting inert carriers and auxiliaries, or searching for inactivating agents and decomposition inhibitors, but these are not necessarily general methods, and A complicated study was required for each compound, and its stabilizing effect was not sufficient.

Many attempts have already been made to stabilize active ingredient compounds by forming them into cyclodextrin inclusion complexes. For example, JP-A-49-71135, JP-A-49-13
No. 4844 and No. 57-142906, regarding the stabilization of agricultural chemical formulations containing a single active ingredient compound,
JP-A-56-75496 and JP-A No. 57-128610 disclose a technique for stabilizing 2'Mi active ingredient compounds by forming one or both of them into a clathrate. .

However, in all of these prior art techniques, stabilization is achieved by forming the active ingredient into a clathrate, and the molar ratio of strine in sifurob to the active ingredient is 0.
It is 5 or more. It is generally believed that the composition of the clathrate is 0.1 to 2.0 as a molar ratio of guest molecules to cyclodextrin. 1 of cyclodextrin
The number of guest molecules included in the molecule is at most two molecules. If the molecular weight of the agricultural chemical active ingredient compound is 300, the molecular weight of β-cyclodextrin is 1135, so even if two molecules are included, in terms of weight ratio, the amount of β-cyclodextrin is approximately twice that of the active ingredient compound. - Cyclodextrin is required. At present, cyclodextrin is extremely expensive, and it is necessary to use more than twice the amount of the active ingredient. It must be said that the economic benefits are small. Furthermore, the process of preparing the clathrate is cumbersome, and the yield of the clathrate is not always good.

On the other hand, JP-A-58-134004 and JP-A-59-1
48708-j) The publication states that β-cyclodextrin y"1o or 50'x is added to 100 parts by weight of 8-hydroxyquinoline steel or streptomycin salts.
Disclosed are agricultural fungicides formulated in quantities. However, the inventions described in these publications are aimed at improving the pesticidal effect and improving the residual effect, and their purposes are completely different from the present invention.

Furthermore, both 8-hydroxyquinoline steel and streptomycin salt are known to be stable, and do not fall under the unstable agricultural chemical active ingredients of the present invention.

7 days, 5 days, 1 day, needle C1 and t-2) Stably retained in a compound containing l/μ We will continue to consider whether to do so.

During the process, the rate of decomposition over time is relatively slow in the initial stage, but accelerates and becomes rapid over time, and when contained alone in a preparation, the rate of decomposition over time is relatively slow. When we investigated the decomposition over time of pesticide formulations containing a combination of different types, we encountered a phenomenon in which decomposition rapidly progressed from a certain stage over time. The authors considered the mechanism by which such chain reaction-like decomposition occurs, and surmised that a certain type of decomposition product may be a causative substance that accelerates the decomposition reaction.

As a result of further investigation into measures to reduce the decomposition-promoting effect of such causative substances, it was surprisingly discovered that the presence of a small amount of cyclodextrin in an agricultural chemical formulation can significantly suppress the decomposition reaction.

A clear conclusion regarding the mechanism by which the decomposition reaction of unstable active ingredient compounds is suppressed by the coexistence of a small amount of cyclodextrin! Although 1N was not obtained, it was inferred that the inclusion of the above-mentioned factor J substance reduces the decomposition promoting effect.

As mentioned above, the present invention does not require the inclusion of active ingredient compounds, but stabilizes it by coexisting a small amount of cyclodextrin in the agricultural chemical formulation, which is essentially different from the prior art using cyclodextrin. Technical philosophy is different.

Cyclodextrin has more than α-1,4 glucose
It is a linked cyclic polysaccharide, and so far it has been classified into α-1β-1γ
-2δ- and branched-cyclofkistri/ are known.

The cyclodextrin used in the present invention may have one or more of these, and there are no restrictions on the manufacturing method or the purity of the cyclodextrin, but β-
Cyclodextrins are preferred. The amount of cyclodextrin to be incorporated into the agricultural chemical formulation is such that the molar ratio to the active ingredient compound is 0.5 or less, since the present invention does not require the inclusion of the active ingredient compound as described above. In addition, the amount should be kept at the minimum level within which the stabilizing effect can be tolerated. When considering effects and economy, the amount is preferably 0.1 mol or less. It is preferable to determine the optimum blending amount based on the types of unstable active ingredient compounds or their combinations.

There is also no particular restriction on the method of blending, and they may be mixed evenly in various agrochemical formulations, or may only be allowed to coexist locally in the formulation.

For example, in the case of an agrochemical irrigation agent, it may be added together with each raw material at the initial stage and mixed and pulverized, or it may be added and mixed after the irrigation agent is prepared, or cyclodextrin may be added and mixed using air-permeable packaging materials. It may be divided into separate packages and placed together in the same packaging as the bulk irrigation agent. A method suitable for the dosage form of each agricultural chemical formulation can be adopted.

The unstable agricultural chemical active ingredient compound referred to in the present invention is not particularly limited, but examples of oxime carbamate compounds include S-methyl-N-C (methylcarbamoyl)oxycothioacetimidate (methomyl), N,N- An example is methyl-2-methyl-carbamoyloxyimino-2-(methylthio)acetamide (oxamyl).

Moreover, as an organic phosphorus compound, 0. o-noethyl 0-(
5-7! Nyl-3-inxazolyl) phosphorothioate (isoxathion), 0.0-methyl 0-(3-methyl-4-nitrophenyl) thiophosphate (fenitrothion), 0-(2-improvyl-4-methyl-
Birimisol-6-) 0.0-noethylthiophosphate (guiazinon), 0,0-tumethyl S-(1,
2-zocarpetoxyethyl) dithiophosphate (malathion), 2-chloro-112,4-nochlorophenyl)vinyl methylphosphate (vinphos)
In particular, in the case of pesticide formulations that combine oxime carbamates and organophosphorus compounds, depending on the combination, the decomposition reaction may be accelerated more than in the case of each individual formulation. The techniques of the present invention are often useful in stabilizing formulations.

In producing the pharmaceutical composition of the present invention, commonly used carriers, surfactants, and other auxiliary agents can be used. Suitable solid carriers include inorganic powders or granules such as clay, talc, kaolin, bentonite, diatomaceous earth, crushed sand, pumice, calcium carbonate, and the like.

Of course, it is also possible to use absorbents, dispersants, wetting agents, potency enhancers, binders, etc. that do not lose the stabilizing effect of the present invention, such as quicklime, calcium chloride, acids, acid anhydrides, - The effects of the present application may be enhanced by co-use with other stabilizers such as regulators, antioxidants, sequestering agents, etc.

Next, some examples of the present invention will be shown, including the dosage form of the present composition,
The blending amount and the like are not limited to those in this example, and can be applied to a wide range of agents such as irrigation agents, powders, granules, and floaglu agents.

It should be noted that all proportions shown in the examples are in parts by weight.

Example 1 33 parts of Calphos original (95 grams of isoxathion),
17 parts of lannate raw material (containing 91% of menmyl), 2 parts of polyoxyethylene alkyl allyl ether, oleyl-
4 parts of sodium N-methyltaurate, 30 parts of white carmen, and β-cyclodextrin (hereinafter referred to as β-CD
As shown in Table 1, mix 2 parts to 14 parts in 2-part stages, and add the remaining clay to 100 parts, mix and crush to make an irrigation agent containing inxathion and methomyl. : Prepared.

Pack each of these irrigation agents into glass bottles, seal them tightly, and
After storing it in a thermostat at 0°C for 4, 8 and 12 weeks, the content of the active ingredient was measured, and the residual rate was calculated based on the content immediately after preparation. -CD molar ratio (2)
Storage period in a thermostat at 40°C -2 (Methomil) (1) Molar ratio of β-CD to methomyl The β-CD-free irrigation agent tested as a comparative example accelerated its decomposition over time; The decomposition of an irrigation agent to which the molar ratio of β-CD to inxathion or methomyl is about 0.05 or more is significantly suppressed.

Example 2 Wettable powders containing inxathion and methomyl were prepared by adding 10 parts of each of Strine, and in the same manner as in Example 1, 4
The residual rate of the active ingredient after storage at 0°C for 12 weeks was determined, and β-
It was compared with the stabilizing effect of CD. The results are shown in Table-3.

Table 3: All α, β, and γ cyclodextrinos are effective.

Example 3 20 parts, 30 parts, or 40 parts of β-CD were added to 60 parts of the raw material of rannate, and white carbon was added to the remainder to make 100 parts.The mixed powder was finely pulverized to obtain 54.6% methomil. A premix containing the following was prepared.

92 parts of crushed calcium carbonate particles sieved with a particle size of 65 to 150 were placed in a water tank mixer, and 4 parts of a liquid mixture of 0.5 parts of ammonium salt of alkyl allyl ether A/sulfuric acid ester was added dropwise and mixed. Next, when the surface of the calcium carbonate particles is uniformly wetted with the Calphos premix, add 3 parts of the above methomyl premix and continue mixing to coat the surface of the calcium carbonate particles. Further, 1 part of white carbon was added and mixing was continued until the fluidity became good and the mixing was stopped.

The thus obtained blended fine granules of inxathion methomyl were prepared in the same manner as in Example 1, and 40%
After storage at ℃ for 4 weeks, 8 weeks, and 12 weeks, the remaining percentage of the effective fraction was determined.

The results are shown in Tables 4 and 5.

Table 4 (Inxathion) Table 5 (Menmil) Example 4 As the active ingredients of the four types of organic phosphorus compounds shown in Table 6, phosphorus equivalent to 33 parts, 17 parts of raninate raw material, 2730 parts of white car, 10 parts of β-CD and clay were added to make 100 parts and mixed and ground to prepare a premix containing an organic phosphorus compound and methomyl. 10 parts of each of these premixes and 90 parts of clay were mixed and ground to obtain a blended powder containing 1 g of β-CD in the formulation.

111iSit, 7'! ：7h-'t'' Reno blended powder was prepared in the same manner as in Example 1, and the residual rate of the active ingredient was measured after 12 weeks at 40°C.9.

Separately, as a comparative example, the residual rate of the active ingredient was measured in the same manner as in the example except that 10 parts of β-CD was replaced with clay, and the results are shown in Table 6 without the addition of J-CD.

The stabilizing effect due to the addition of β-CD was remarkable.

Table 6 Example 5 Add 92 parts of the calcium carbonate grains used in Example 3 to a tin mixer, and while continuing to mix, mix the diazonone premix (3.5 parts of the raw material containing 95 parts of diazonone).
When the surface of the calcium carbonate particles was uniformly wetted,
2.5 parts of Menmil premix (mixture and pulverization of 70 parts of rannate a-form and 30 parts of β-CD) prepared separately from fA was added to coat the surfaces of the calcium carbonate particles. Further, 1.5 parts of white carmen was added and mixed to obtain a fine granule containing diazinon and menmyl with good fluidity.

The molar ratio of β-CD to diazinon and methomyl was 0.060 and 0.067, respectively, and by incorporating such a small amount of β-CD, the stabilizing effect of the main agent over time was satisfactory.

Example 6 93 parts of sub-granular pumice sieved into 10 to 28 meshes was charged into a Nautami mixer, and while mixing was continued, 5 parts of pidate stock solution (aqueous solution containing 20% oxamyl) and N,N-methylformamide were added. Two parts were dropped and adsorbed to prepare oxamyl granules.

Put 100 t of this granule into a 200-mm glass bottle, pack each weight of β-CD shown in Table 7 into a breathable paper bag, place it on top of the granule in the bottle, and seal it tightly. After being stored in a thermostat at 40°C for 4, 8 and 12 weeks, the oxamyl content was measured and the residual rate relative to the content immediately after preparation was calculated.

The results are shown in Table-7.

Table 7 Example 7 91 parts of the sub-granular pumice used in Example 6 was charged into a Nauta mixer, and while mixing, 5 parts of the pidate stock solution was dropped and adsorbed. After the adsorption is completed, add 3.2 parts of calphos drug substance and inpropyl phosphate (mixture of mono-isomer and iso-isomer).
0.8 parts of awm was mixed and adsorbed to prepare granules containing oxamyl inxathion.

After storing 100 vol of this blended granule over time in the same manner as in Example 6, the content of the active ingredient was measured to determine the residual rate. The results are shown in Table-8 and Table-9.

Table 8 (Oxamyl) Table 9 (Inxathion) As shown in Examples 6 and 7, the same package of β-CD was
It was possible to suppress the decomposition reaction even if it was only allowed to coexist within the packaging.

Claims (7)

[Claims] (1) In a pesticide formulation containing one or more unstable pesticide active ingredients, the molar ratio to the active ingredient compound is 0.
．． A stabilized agricultural chemical composition characterized in that an amount of cyclodextrin of 5 or less is present. (2) The agrochemical composition according to claim 1, wherein the molar ratio of cyclodextrin to the active ingredient compound is 0.1 or less. (3) The agricultural chemical composition according to claim 1, wherein the cyclodextrin is β-cyclodextrin. (4) The agricultural chemical composition according to claim 1, wherein the unstable agricultural chemical active ingredient compound is an oxime carbamate compound. (5) The oxime carbamate compound is S-methyl-N-
The agricultural chemical composition according to claim 4, which is [(methylcarbamoyl)oxy]thioacetimitate or N,N-dimethyl-2-methylcarbamoyloxyimino-2-(methylthio)acetamide. (6) The agricultural chemical composition according to claim 1, wherein the unstable agricultural chemical active ingredient compound is an organic phosphate compound. (7) The agrochemical composition according to claim 1, wherein the unstable agrochemical active ingredient compound is a combination of an oxime carbamate compound and an organic phosphate compound.