WO1995028835A1

WO1995028835A1 - Process for producing pesticide-containing wax matrix and agricultural preparation

Info

Publication number: WO1995028835A1
Application number: PCT/JP1995/000780
Authority: WO
Inventors: Kouichi Nakamichi; Shougo Izumi; Hiroyuki Yasuura
Original assignee: Nippon Shinyaku Co., Ltd.
Priority date: 1994-04-21
Filing date: 1995-04-20
Publication date: 1995-11-02

Abstract

A process for producing a pesticide-containing wax matrix capable of coping with environmental changes, which comprises treating a number of waxes having different properties and a pesticide as the essential ingredient in one batch on a multi-screw extruder. As the waxes having different properties can be mixed with one another sufficiently homogeneously, the pesticide can be released in a highly controlled manner.

Description

Two

It is manufactured by a technique of dispersing a pesticide, cooling and solidifying it, and granulating and crushing it (so-called melting method; Japanese Patent Application Laid-Open Nos. 56-30901 and 57-38702; Such. ) . In this manufacturing method, it is not possible to finally melt and mix the hydrophobic and hydrophilic resins in a sufficiently uniform manner, and also to use a device capable of accurately controlling the cooling temperature to sufficiently uniform the resins having different melting points. It is difficult to mix. The need to rely on equipment that can accurately control the temperature would increase manufacturing costs, in particular against the cost savings required in the field of agrochemicals.

On the other hand, a multi-screw extruder is a screw-type kneading extruder in which multiple screws can entangle and interfere with each other to generate physically high energy. This multi-screw extruder is a machine that has completely different performance and applications from single-screw extruders, because it can perform processing on raw materials that cannot be obtained with single-screw extruders. be able to. Multiaxial extruders have developed mainly in the food and plastic fields, and are widely used in the processing of food (cereals, proteins, livestock meat, fish meat, etc.) and injection molding of plastic. Recently, its use in the pharmaceutical field has been reported (PCT W092 / 18106, PCT W094 / 08568, PCT W095 / 05809, etc.).

The single-screw extruder is a screw-type kneading extruder whose main functions are simple mixing and granulation operations, so no further effects can be expected. It is thought that it is difficult to mix these with uniformity.

Disclosure of the invention Three

An object of the present invention is to provide a method for producing pesticide-containing ヮ xmatrictus which can respond to environmental changes such as changes in temperature and changes in soil moisture more than conventional pesticide-containing ヮ xmatrices. Specifically, the pesticide-containing マ xmatrix, in which the release of pesticides from the wax matrix and the melting temperature of the wax matrix itself, is highly controlled, can be achieved in a practical and economical manner. It is to provide a manufacturing technology that can be manufactured.

The present inventors have studied various uses of a multi-axial type extruder (hereinafter simply referred to as “extruder”), and have found a method for producing pesticide-containing xumatritus, which can achieve the above object. Completed the invention.

Hereinafter, the present invention will be described in detail.

The present invention is a method for producing a pesticide-containing wax matrix, characterized in that a plurality of pesticides having different physical properties and a pesticide are used as essential components and processed collectively by an extruder.

Here, the term “wax” refers to not only wax in the narrow sense of “high-alcohol esters of high-fatty acids” but also wax in a broad sense, ie, 40-90 ′ with the properties of wax (plasticity, glossiness, opacity, etc.). It also means a substance that melts in C.

タス Examples of the physical properties of a tas include melting point, solubility in water (hydrophobic, hydrophilic).

Examples of the wax according to the present invention include natural waxes derived from animals and plants, natural waxes derived from petroleum oil or minerals, and synthetic or semi-synthetic waxes *. Hydrophobic wax, hydrophilic pack Four

Any of these can be used.

Hydrophobic waxes include, for example, carnauba wax, wood wax, black wax, wool wax, microcrystalline wax, polyethylene wax, chlorinated naphthalene wax, hydrogenated castor oil, hydrogenated rapeseed oil, beeswax, stearic acid, paraffinic wax. Examples include wax, beef tallow, and cocoa butter.

Examples of hydrophilic waxes include polyethylene glycol 20,000, polyethylene glycol 6,000, polyethylene glycol 4,000, polyethylene glycol 2,000, polyethylene glycol 1,540, and polyethylene glycol. 1,000,000 Polyoxyethylene [105] Polyoxypropylene [5] Glycol, Polyoxyethylene [160] Polyoxypropylene [30] Glycol, Polyoxyethylene [196] Polyoxypropylene [67] Glycol And so on.

A pesticide-containing paint matrix can be produced by combining two or more of the above paints. Conventionally, it is possible to arbitrarily combine a hydrophobic box and a hydrophilic box, which has been difficult.

The total mixing ratio of wax varies depending on the type of wax used, the type of pesticide or additive, the type and type of extruder, etc., but can be 10 to 99.999% (w / w). Preferably, it is 50-99.9% (w / w), more preferably 90-99.9% (w / w).

The mixing ratio of each box can be arbitrarily set depending on the desired pesticide release rate, melting temperature, and the like. In general, increasing the ratio of hydrophilic wax can speed up the output of pesticides. Also Five

The melting temperature of the wax matrix itself can be increased by increasing the ratio of the wax having a high refractive index.

There is no particular limitation on the types of pesticides that can be applied in the present invention. Any of insecticides, fungicides, herbicides, etc. can be applied. Specifically, insecticides such as ethiofundalp, benfracarp, carbofuran, aldirube, acephate, diazinon, imidacloprid, benomyl, thiophanate methyl, hexaconazole, isobrothiolane, furaside, Fungicides such as penconazole, fludizazole, vitelenol, buventenazole, triazimefone triazimenol, triflumibule, tricyclazole, josetilamino, etaconazol, etc., mefenacet, falacurl, metrachlor, atrazine And herbicides such as cyanadine, trifluralin and the like.

Pesticides can be used alone or in combination of two or more. The mixing ratio of the pesticide varies depending on the type of pesticide, the type of wax and additive used, the type and type of extruder, etc., but can be 0.001 to 50% (w / w), which is preferable. Is 0.01% to 20% (w / w), more preferably 0.1% to 10% (w / w).

In addition, additives such as cellulose derivatives, starch, starch derivatives, saccharides, inorganic substances, and mineral substance carriers can be added as necessary. Specifically, for example, the following can be mentioned.

1. Cellulose derivatives

Microcrystalline cellulose, microcrystalline cellulose, carboxymethylcellulose sodium, methylcellulose, ethylcellulose, hydroxyb 6

Methyl pill cellulose, low-substituted hydroxypropyl pill cellulose, hydr xybu pill methyl cellulose 228, hydroxypropyl pilmethyl cellulose 290, hydroxypropyl methylcellulose 290, hydroxy pill pill Methylcellulose acetate succinate, carboxydimethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium.

2. Starch and its derivatives

Wheat starch, corn starch, corn starch, dextrin, alpha-starch, partially alpha-starch, carboxymethylstarch sodium, bullrun.

3. Sugars and sugar alcohols

Sucrose, mannitol, xylitol, sorbitol.

4. Inorganic and mineral carrier

Kaolin, talc, magnesium stearate, titanium oxide, precipitated calcium oxide, calcium hydrogen phosphate, clay, bentonite, diatomaceous earth, white carbon.

5. Plasticizer

Triethyl citrate, triacetin, medium fatty acid triglyceride, propylene glycol.

6. Other

Soybean oil, beannut oil, sesame oil, rapeseed oil, camellia oil, olive oil, peanut oil, Uyuri oil.

These additives can be incorporated up to 50% (w / w).

The main part of the extruder is a barrel called a barrel, equivalent to an exit 7

It mainly consists of a die and a screw mounted with various screw elements. There are usually multiple barrels through which the screw passes. The screw elements include trapezoidal screw elements, trapezoidal cut screw elements, trapezoidal reverse cuts, ball screw elements, needing paddles (kneading discs), and any combination of them. Can be performed. The components sent into the barrel are moved in the barrel by a screw, and are subjected to processing such as shearing and mixing by a screw element such as a kneading paddle in the barrel, and are extruded from the pores of the die. Normally, each barrel and die can be independently temperature controlled.

In the present invention, it is provided with basic characteristics such as (1) a function of transporting water and oil, (2) a mixing function, a shearing function, a compressing function, a crushing function, and a heating function, which are generally used in the food and plastic fields. Any extruder can be used as is. It should be noted that a wax matrix according to the present invention can be manufactured sufficiently by using a biaxial extruder having two screws.

There are various types of evening extruders, such as non-interlocking different direction or co-rotating extruder and full or partially interlocking different direction or co-rotating extruder. In the present invention, a completely interlocking co-rotating extruder is preferable, and a fully interlocking co-rotating twin-screw extruder having a needling paddle (kneading disc) on the shaft is particularly preferable. preferable.

Batch processing in the extruder applies to all barrels in the extruder. 8

And not necessarily in the die. The batch matrix according to the present invention can be sufficiently manufactured by performing batch processing in and after a certain barrel.

Here, “collective processing” means that all the raw materials are subjected to shearing, mixing, kneading, and extrusion at substantially the same time.

The method of batch processing of raw materials with an extruder is as follows: ① All raw materials (wax, pesticide, other additives) are simply mixed in advance, and this is supplied from the main supply hole of the extruder and batch processed. , ② A method of pre-mixing some raw materials among the raw materials, supplying them through the main supply hole of the extruder, and supplying the remaining raw materials through the auxiliary supply holes, and performing batch processing. For example, a method of supplying one raw material j from the main supply hole of the extruder and supplying the “remaining raw material” from the auxiliary supply hole to collectively process the raw material j can be used. Of these methods, ①② is preferred.

Here, the main supply hole refers to the most basic supply hole for supplying raw materials into the barrel, and the auxiliary supply hole refers to a main supply hole capable of supplying auxiliary components to the barrel in an auxiliary manner. A supply hole other than the supply hole.

In the above item (2), if necessary, any raw material can be further supplied from the auxiliary supply hole.

In (1) above, for example, wax and pesticides can be (some) raw materials j, and other additives can be r remaining raw materials j. In any case, the present Pixmatrix can be obtained. Preferably, the wax is one of the "several ingredients". "The remaining raw material J can be supplied as a mixture from one auxiliary feed hole, 9

Individual raw materials or mixtures of arbitrary raw materials can be supplied from a plurality of auxiliary supply holes. It should be noted that one or more of the raw materials J supplied from the main supply hole can be included in the “remaining raw material” and supplied from the auxiliary supply hole.

In (3) above, (1) It is preferable that one raw material J is wax, and the “remaining raw material” can be supplied as a mixture from one auxiliary supply hole, or individual raw materials or arbitrary raw materials can be supplied. Can be supplied from a plurality of auxiliary supply holes. It should be noted that a part of the primary raw material j supplied from the main supply hole can be included in the remaining raw material j and supplied from the auxiliary supply hole.

Simple mixing of the raw materials can be performed by a machine such as a kneader mixer, a V-type mixer, a double cone type mixer, a cubic type mixer, a ribbon type mixer, or manually.

The supply of the raw material into the barrel can be performed manually or by a raw material feeder generally provided in the extruder to be used, but there is no particular limitation as long as the equipment can supply the raw material at a constant speed. It can be carried out. Examples of such an apparatus include a screw feeder, a table feeder, a slurry feeder, a pressure feeder, a belt conveyer-type quantitative feeder, and a magnetic feeder.

Next, the processing conditions of the extruder will be described.

The temperature of the barrel and die of the extruder can be appropriately set according to the type of wax used. Normally, a temperature about 5 to 30 ° C lower than the melting point of the wax with the highest melting point among the waxes used. Ten

Preferably, the temperature can be set as low as about 10-20. In some cases, the wax matrix according to the present invention can be obtained even at a higher temperature, but at a higher temperature, the wax usually comes out of the die in a molten state, so that any shape can be obtained. It is difficult to obtain a molded body of

The screw rotation speed (processing speed) can be set as appropriate depending on the type and type of extruder, raw material, screw shape, etc. It can be set within the allowable range of the extruder used. . The longer the barrel is, the longer the extruder can be. The longer the total length of the barrel, the better the processing capacity such as mixing and shearing. Specifically, 50 rpm or more is appropriate, and 50 to 300 rpm is preferred.

Discharge pressure, 10~150kg / cm ² is suitably, 30~120kg / cm ² is favorable preferable.

The shape and combination of the screw elements that can be used can be selected without any particular limitation. However, it is preferable to use one or more kneeling paddles (kneading discs) having strong kneading action and shearing action.

The discharge die can be appropriately changed depending on the purpose. Specific examples include a circular discharge die having various diameters for obtaining a columnar processed product, and a flat discharge die for obtaining a plate-like processed product.

Preparations containing Pexmatrix produced by the present invention are also included in the present invention. The formulation is not particularly limited <Specific examples include powders, powders, tablets and the like. 1 1

The preparation according to the present invention can be produced as follows. The raw material batch-processed by the extruder is continuously extruded from the pores of the die as the composition of the present invention. This can be cut to a desired length by a suitable cutting machine, for example, a roller-type crusher, a cutter mill, a pin mill, or the like. This cut product can be used as it is as a granular preparation of the present invention. In addition, the wax matrix of the present invention extruded from the pores of the die is used, for example, by a rotary cutter equipped at the tip of the die (for example, a rotary cutter for KBXN-30 manufactured by Kurimoto Iron Works). By cutting to a desired length, a granular preparation of the present invention can be obtained directly without any special manipulation.

The tablet-form preparation of the present invention can be obtained by compression-molding the cut-off granular Matrix according to the present invention.

Furthermore, the present invention may also include those obtained by applying a coating treatment or the like to Pex Matrix extruded from the pores of the die, cut granular Pex Matrix, or compression-molded Pex Matrix tablets. it can.

The invention's effect

(1) According to the present invention, a plurality of powders having different physical properties can be mixed sufficiently uniformly, and the release of the pesticide from the wax matrix and the melting temperature of the wax matrix itself are highly controlled. Pexmatrix can be manufactured. Therefore, it is possible to provide a pesticide-containing extract matrix suitable for the situation (seasonal) at the time of spraying, such as the temperature at the time of spraying and the amount of soil moisture. In addition, it is possible to manufacture pesticide-containing plex-matrix that releases pesticides at any temperature. 12

As a result, pesticides containing pesticides containing pesticides can be provided that release pesticides when the temperature reaches a temperature at which pests and diseases easily occur, and suppress the release of pesticides when the temperature drops.

(2) The production method according to the present invention can be applied to all pesticides.

(3) The manufacturing method according to the present invention is convenient in practical and economical aspects.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples. Barrel numbers are assigned in ascending order from the barrel on the sample supply side (entrance side).

Example 1

4 g of Mefenaset, 280 g of Carnauba wax powder, and 120 g of polyethylene glycol powder are mixed for 15 minutes using a glass V-type mixer for 15 minutes, and the diameter is 32 mm 0, effective LZD. : 20, screw element pattern: 16P, 12P, 9.6P, 8P, 30deg: 2-axis type with 3x8tx, 1mm 0x5 hole die Using a truder (KE XN—30S—20, manufactured by Kurimoto Iron Works, same hereafter), set the barrel 1 to 25 and the barrels 2, 3, 4, 5 and the die to 63. Then, the mixed powder was put into the main supply hole by a hopper at a speed of 40 g per minute, and extruded at a screw rotation speed of 80 rpm to produce a Pex matrix according to the present invention. .

Example 2

Mix 4 g of Megurnaset, 200 g of Carnauba wax powder and 200 g of polyethylene glycol 10000 powder in a glass V-type mixer for 15 minutes, and remove barrel 1 of a twin-screw extruder. twenty five. C, Nokrel 2, 13

3, 4 and 5 and the die were set to 55, and the same conditions as in Example 1 were applied to manufacture a Pex Matrix according to the present invention. Example 3

4 g of Mefenaset, 120 g of Carnauba wax powder and 280 g of polyethylene glycol powder are mixed in a glass V-type mixer for 15 minutes, and the barrel 1 of the twin-screw extruder is mixed with 2 g. In 5, the processing was performed under the same conditions as in Example 1 except that the barrels 2, 3, 4, and 5 and the die were set to 55'C, to produce a PEX matrix according to the present invention. Example 4

A mixture of 5 g of Mefenaset, 350 g of Raffinwax, 100 g of cacao butter, 100 g of cocoa butter, and 50 g of powdered polyethylene glycol, was mixed with a glass V-type mixer for 15 minutes. Axial extruder barrel 1 was set at 25, barrels 2, 3, 4, 5 and die were set at 35, the extrusion speed was set at 100 rpm, and processing was performed under the same conditions as in Example 1. Performed The Pex Matrix according to the present invention was manufactured.

Example 5

A mixture of 5 g of Mephenaset, 350 g of ノ, raffin wax, 50 g of cocoa butter, 100 g of polyethylene glycol, and 100 g of powder of 1500 g was mixed with a glass V-type mixer for 15 minutes. Was processed under the same conditions as in Example 4 to produce a wax matrix according to the present invention.

Example 6

A mixture of 5 g of mefenacet, 250 g of Raffinwax, 250 g of cocoa butter, 200 g of cocoa butter, and 500 g of polyethylene glycol 150 g was mixed with a glass V-type mixer for 15 minutes. Axle extruder barrel 1 14

In step 25, the nozzles 2, 3, 4, 5 and the die were set to 33'C, and processing was performed under the same conditions as in Example 4 to produce a black matrix according to the present invention. did.

Example 7

A mixture of 5 g of Mephenaset, 250 g of Raffinwax, 150 g of cocoa butter, 150 g of polyethylene glycol, and 100 g of powdered polyethylene glycol for 15 minutes using a glass V-type mixer. This was processed under the same conditions as in Example 6 to produce an exhaust matrix according to the present invention.

Example 8

A mixture of 5 g of Mephenaset, 250 g of Raffin Wax, 250 g of Raffin Wax, 100 g of cocoa butter, and 150 g of Polyethylene Glycol 1500 g in a glass V-type mixer was mixed for 15 minutes. barrel 1 of biaxial Ekusu Toruda the 2 5 ^e C, Bruno, * rel 2, 3, 4, 5 and other set the die 3 4, the present invention performs processing under the same conditions as in example 4 The Pixmatrix according to the above was manufactured.

Example 9

A mixture of 5 g of Mephenaset, 250 g of Raffin Wax, 250 g of cocoa butter, 50 g of cocoa butter and 200 g of Polyethylene glycol 150 g was mixed with a glass V-type mixer for 15 minutes. Was processed under the same conditions as in Example 8 to produce an exhaust matrix according to the present invention.

Example 10

A mixture of 5 g of Mefenaset, 150 g of Paraffin Wax, 300 g of cocoa butter, and 500 g of polyethylene glycol 150 g in a glass V-type mixer for 15 minutes to form a 2-axis type Extruder barrel 1 Fifteen

In step 25, the barrels 2, 3, 4, and 5 and the die were set to 3C, and processing was performed under the same conditions as in Example 4 to produce a cell matrix according to the present invention.

Example 1 1

Mephenaset 5 g, paraffin wax 150 g, cocoa butter 2

50 g of polyethylene glycol 150 g powder and 100 Og powder were mixed for 15 minutes in a glass V-type mixer, and the mixture was treated under the same conditions as in Example 10 to give a wax according to the present invention. Manufactured matrix.

Test example 1

Using edible blue No. 1, which is a water-soluble pigment, as a marker, the operability of the method of the present invention and the conventional method, the appearance and uniformity of the content of wax matrix citrus were compared and examined. The results are shown in Table 1.

Samples of the present invention:

In addition to using 4 g of edible blue No. 1 pigment in place of Mehnaset, treatment was performed under the same conditions as in Example 2 to obtain a sample of the present invention.

Conventional sample:

A mixed powder having the same composition as that of the sample of the present invention was put into a transparent glass beaker (diameter: 11.6 cm, height: i 6 cm), and was heated and melted in a warm bath heated to 90 ° C. The mixture was stirred and mixed with a spatula. After that, the beaker was taken out, allowed to stand in an environment of 25'C, and allowed to cool naturally, thereby producing a Pexmatrix for a comparative test (natural cooling method). A powdered mixture of the same composition was placed in a stainless steel beaker (diameter 20 cm, height 2).

6 cm) and melted by heating in a warm bath heated to 90'C, then taken out under a 25'C environment. 16

Stir-mix cooling operation was performed using a motor stirrer (1200 RTS; manufactured by Shinto Kagaku) to prepare a Pex matrix for a comparative test (stir-mix cooling method).

table 1

(n = 3,% ± S.D.) As shown in Table 1, it is clear that the method sample of the present invention is superior to the conventional method sample in terms of operability, appearance of the composition, and content uniformity.

Test Example 2 Dissolution test (1)

The wax matrix produced by the method of the present invention and the Pex matrix produced by the conventional stirring-mixing cooling method were used with a roll granulator (GRN-101 type; manufactured by Nippon Grannyle Ichiyu Co., Ltd .; the same applies hereinafter). The particles in the range of No. 16 (1000) to No. 30 (0000) were used as samples for the dissolution test. 60 mg of each of these samples was treated with 30 mg of purified water 9 0 ml, and the paddle method (Pad 17

The number of elutions of Blue No. 1 was measured over time under the conditions of a rotational speed of 100 rpm and a measurement wavelength of 629 nm. The results are shown in Table 2.

Table 2

(n-3,% ± S.D.) As shown in Table 2, there is no great difference between the elution rates, but it is clear that the variation is much smaller in the wax matrix of the present invention.

* Variation scale

Each was measured three times in accordance with the dissolution test method described above, and the standard deviation was obtained, which was used as a measure of variation.

Test example 3 Melting point measurement and dissolution test (2)

1> The wax matrix according to the present invention manufactured according to Examples 1, 2, and 3 was crushed using a roll granule, and the wax matrix was mixed with a No. 16 (100 〃) to a No. 30 (50) The melting point was measured using a melting point instrument with a micro-gun.For the dissolution test, the above sample was dissolved in 3 (900 ml of purified TC water). The elution amount of mefnaset was measured over time under the conditions of the paddle method (paddle rotation speed: 100 rpm) of the Japanese Pharmacopoeia, and the results are shown in Table 3. 18

Table 3

(%)

As shown in Table 3, the melting point of the Pex Matrix obtained by the method of the present invention indicates a temperature change relative to the composition ratio of the Pex used, and a Pex Matrix having a desired melting temperature is obtained. Things have come. Also, the release rate increased as the amount of the polyethylene glycol added increased. From this, it was found that release control was possible by changing the composition ratio of hydrophilic and hydrophobic resins.

2) The wax matrix of the present invention according to Examples 4, 6, 7, 10 and 11 was crushed by using a roll granule, and the wax matrices Nos. 16 (100) to 30 (50) were crushed. 0) The particles in the range were used as samples for the dissolution test. Melting points were measured using a melting point instrument with a microgun. For dissolution test. Put the above sample into 900 ml of 3O'C purified water, and elute mefnaset over time under the paddle method of Japan Pharmacopoeia (paddle rotation speed: 100 rpm). The amount was measured. The results are shown in Table 4. 19

Table 4

As shown in Table 4, the melting point of the wax matrix can be controlled to a commercial value by changing the composition ratio of three types of waxes (paraffin wax, cocoa butter, and polyethylene glycol) with different melting characteristics and melting points. In addition, it was found that a drug release was also provided by a Pexmatrix exhibiting the same melting point, and that a rapid drug release was observed when tested at the melting point temperature of wax matrix. It has been found that opposing drug release can be promoted.

Claims

20 Scope of Claim

1. A method for producing pesticide-containing wax matrix, which is characterized by batch processing of multiple waxes and pesticides having different physical properties as essential components using a multiaxial extruder.

2. A method for producing pesticide-containing wax matrix, which is characterized by batch processing of multiple waxes and pesticides having different melting points as essential components using a multi-axial extruder.

3. A method for producing pesticide-containing wax matrices, which is characterized in that hydrophobic wax, hydrophilic wax and pesticide are essential components and are processed collectively by a multiaxial extruder.

4. The method for producing pesticide-containing ヮ xmatritsutus according to claims 1 to 3, wherein the multi-axial extruder is a biaxial extruder.

5. A preparation containing a pesticide-containing pesticide produced by the production method according to claims 1 to 4.