RU2147179C1 - Dosed pesticidal agent in the form of single pressed mold - Google Patents

Abstract

FIELD: agriculture. SUBSTANCE: described is pesticidal agent in the form of single pressed mold comprising active ingredient which is hard at 25 C, poorly soluble in water, disintegrating polyvinyl pyrrolidone based agent, dispersing agent, wetting agent and additional substances and which is capable of being decomposed when added into sufficient amount of water to form pesticide suspension. Pesticidal agent comprises 5- 60 wt parts of pesticides with particle size of less than 5 microns and 25-50 wt parts of polyvinyl pyrrolidone. EFFECT: pesticidal agent can be easily restored when dropped on ground unlike liquid or powder-like agents. 6 cl, 5 ex

Description

 The invention relates to a dosed agent, as well as to a method for producing a dosed agent and treating it with an article or locus.

A method of manufacturing a dosed agent includes:
mixing at least one active ingredient, which is in solid form at 25 ^° C. and which has an average particle size of less than 5 microns, with a disintegrating agent to form a compressible mixture; and
pressing the mixture into a single dosage agent.

 This method may include grinding the active ingredient in solid form and having an average particle size of more than 5 microns, in order to obtain particles with an average size of less than 5 microns. The active ingredient should preferably be crushed to particles with an average size of 1-3 microns. Grinding can be carried out by dry grinding the active ingredient, for example by micronization, to particles of the desired size. The ground active ingredient can then be mixed with a particulate disintegrant. Another embodiment of the present invention is that grinding (wet) can be carried out by preparing a suspension of the active ingredient in a suitable liquid carrier in which the active ingredient is insoluble or sparingly soluble, and wet grinding the suspension concentrate to obtain particles of the active ingredient of the desired size. Then the suspension concentrate can be mixed with a disintegrating agent by incorporating it into a disintegrating agent. However, if desired, the ground suspension concentrate may be spray dried and then mixed with a disintegrant.

 Although the active ingredient may be any suitable active ingredient, such as a therapeutic agent, anthelmintic, pigment or dye, etc. The Applicant believes that this method will find particular use (but not the only one) in the manufacture of dosage forms in which the active ingredient is pesticide, e.g. insecticide, herbicide, fungicide, etc.

The pesticide can be a pesticide that is sparingly soluble in water, so water can be used as a liquid carrier in the formation of a suspension concentrate, and the concentration of the pesticide in water in a suspension concentrate is thus higher than the solubility limit of the pesticide in water. The pesticide may have a solubility in water at 25 ^° C. of less than 1000 mg / L, preferably less than 50 mg / L. Preferably, the pesticide has a melting point above 70 ^o C.

 The pesticide may be a herbicide such as atrazine (atrazine), simazine (simazine), cyanazine (cyanazin), tributylazine (terbuthylazine), diuron (diuron), chlorosulfuron (chlorsulphuron), metsulfuron (metsulfuron), tralkoxide (2-chloro-4-mesylbenzoyl) cyclohexane-1,3-dione; an insecticide such as deltamethrin (deltamethrin), lindane (lindane), carbaryl (carbaryl), endosulfan (endosulfan) or carbofuran (carbofuran); a fungicide such as methylthiophanate (thiophanate methul), carbendazim (carbendazim), flutriafol (flutriafol), hexaconazole (hexaconazole), chlortalonil (chlorothalonil), copper chloride, captan or thiram (thiram); or an acaricide such as hexithiazox (hezyrhiazox), cyhexatin (cyhexatin), or amitraz (amitraz).

Dosage may contain, by weight:
active ingredient 5 to 60 parts;
self-disintegrating agent 20 to 70 parts.

 The disintegrant may be able to disintegrate by vigorous evolution of gas or swelling upon contact with water. If it is capable of swelling on contact with water, then it may be crosslinked polyvinylpyrrolidone, which also works as a binding agent. For example, crosslinked polyvinylpyrrolidone may be available under the trademark POLYPLASDONE XL manufactured by GAF Corp, or available under the trade name KOLLIDON CL manufactured by BASF. However, it can be any other suitable disintegrant capable of swelling upon contact with water, such as modified cellulose gum, for example, available under the trade name AC-DI-SOL, manufactured by FMC Corporation, or sodium starch glucolate, such as available under the trade Name EXPLOTAB manufactured by Protea Chemical Services. In cases where the disintegrant is capable of violently emitting gases in contact with water, it may be a combination of an acid and a base, such as a combination of tartaric acid and an alkali metal carbonate or bicarbonate, such as sodium bicarbonate.

 The method may also include mixing at least one additional substance with the active ingredient before and / or after grinding. So, in cases where a suspension concentrate is formed, this method may include adding at least one dispersant to the suspension concentrate before wet grinding. When wet grinding is carried out, the dispersant can be added before or after grinding. The dispersant may be a surfactant, commonly used in the preparation of a wettable powder or suspension concentrate, for example sodium lignosulfonate; condensate of sodium salt of naphthalenesulfonic acid and formaldehyde; sodium alkylaryl sulfonate; a condensate of nonyl phenol and alkylene oxide such as nonyl phenol ethylene oxide or nonyl phenol ethylene oxide / propylene oxide; sodium lauryl sulfate, which acts as a wetting agent, available under the trade name EMPICOL LZ, manufactured by Lankro; a condensate of the sodium salt of naphthalenesulfonic acid and formaldehyde, available under the trade name TAMOL NNO, a derivative of BASF; hydroxyethylated polyarylphenol phosphate, which is an aqueous dispersing agent and an example of which is a compound obtained from Rhone-Poulenc under the trade name SOPROPHOR FL; sodium diisopropylnaphthalenesulfonate, which acts as a wetting agent and is available under the trade name AEROSOL OS, manufactured by Cyanamid and the like.

The additional substance may be different or also include one or more of the following components:
an absorption carrier, such as colloidal silicon dioxide, for example AEROSIL 200 (trade name), diatomaceous earth or clay, such as attapulgite;
- a binder, such as micronized cellulose, for example, as available under the trade name ELCEMA P100, manufactured by Degussa, and which also acts as a filler and disintegrant; or lactose monohydrate, which, for example, is obtained under the trade name LUDIPRESS from BASF and which is a direct adjunct in tabletting;
- a lubricant such as magnesium stearate;
- a flow improver, such as absorption silicon dioxide, for example SIPERNAT 22S (trade name), manufactured by Degussa and which is silicon dioxide, ground and spray dried, and which acts as a substance that promotes free flow and prevents sintering; and
- a water-soluble excipient, such as water-soluble starch, urea, or sodium chloride.

Dosage may contain by weight:
active ingredient - 5 - 60%
binding agent - 10 - 30%
flow improver - 0.5 - 10%
wetting / dispersing agent - 0.5 - 5%
disintegrating agent - 3 - 50%
lubricant - 0.05 - 2%
filler - 2 - 30%
The present invention also extends to a dosage agent that is manufactured according to the method.

According to another aspect of the invention, there is provided a dosage form that is in a single compressed form and which contains a mixture of the active ingredient, which is in solid form at 25 ^° C. and whose average particle size is less than 5 microns, with a disintegrant.

Also proposed is a method of processing an article or locus, which includes:
introducing the dosage agent of the present invention into a predetermined volume of water, the volume of water being such that the concentration of the active ingredient in water is higher than the solubility limit of the active ingredient in water;
the disintegration (disintegration) of the dosed agent, leading to the formation of the active ingredient in water; and
applying a suspension to the product or locus to be treated.

Below this invention is described using non-limiting examples (all proportions are given in parts by weight):
Example 1
Stage 1

A suspension concentrate having the following composition was made by mixing the following components:
technical methylthiophanate (purity 93%) (equivalent to 40.08 parts of the active ingredient) as an active ingredient - 43.10
as a dispersing agent TAMOL NNO - 3,50
as an additional dispersant TERIC 200 (trade name), which is a condensate of nonylphenol and alkylene oxide, manufactured by ICI Australia - 1.50
as an anti-foaming additive, SILCOLAPSE 5000A (trade name), which is an anti-foaming silicone, obtained from ICI - 0.04
water - 51.86.

 The suspension concentrate was crushed by passing it twice through a horizontal ball mill (laboratory model KDL Dyno-mill) to obtain solid particles, the average size of which was 2 microns.

 Stage 2

Molded tablets having the following composition:
suspension concentrate from stage 1 (equivalent to 35.0 parts of the active ingredient) - 87.32
as a wetting agent EMPICOL LZ - 1,0
as a fluidity improver, SIPERNAN 22S - 0.5
as a disintegrating agent POLYPLASDONE XL - 40.9
as a binder, ELCEMA P100 - 15.4
as a lubricant, magnesium stearate is 0.1.

In order to make tablets, the following steps were carried out:
(i) The suspension concentrate was included in a disintegrant;
(ii) This mixture was granulated by passing it through sieves (British Standard Sieve, 16 mesh);
(iii) Then these granules were dried in a vacuum oven at 70 ^o C;
(iv) The remaining components were mixed with dried granules; and
(v) The mixture was pressed into tablets weighing 2.5 g under a pressure of 1 ton.

Thus, each tablet contained 0.875 g of active ingredient. When consumed, 1 tablet is added to 1 liter of water having an ambient temperature of, for example, 25 ^° C. The tablet disintegrates in 30 seconds to form a suspension of the active ingredient in water. Examination of the suspension under a microscope showed that most of the suspended particles had a size in the range of 1-3 microns.

Example 2
Stage 1

 A suspension concentrate having the composition shown below was prepared and crushed as described in Example 1.

technical hexaconazole (purity 87.3%) (equivalent to 20 parts of the active ingredient) - 22.9
TERIC 200 - 2.6
SILCOLAPSE 5000A - 0.1
water - 74.4
Stage 2

 Tablets having the composition below were made according to the procedure of Example 1, except that the dispersant was added to the milled suspension concentrate before it was included in the disintegrating agent.

suspension concentrate from stage 1 (equivalent to 30 parts of the active ingredient) - 150.0
POLYPLASDONE XL (disintegrant) - 58.4
SOPROPHOR FL (Dispersing Agent) - 3.1
magnesium stearate - 0.1
When the resulting tablets were dispersed in ordinary hard water containing 340 ppm. calcium in the form of calcium carbonate, to a concentration of the active ingredient of 0.005%, then after 30 minutes 88% of the solid passed into the suspension.

 Example 3

 Stage 1

 A suspension concentrate having the composition indicated below was prepared and ground as described in Example 1.

technical deltamethrin (98% purity) (equivalent to 64 parts of the active ingredient) - 65.31
TERIC 200 - 2.73
SILCOLAPSE 5000A - 0.08
water - 31.47
Stage 2

 Tablets having the composition below were made according to the procedure of Example 1, except that the mixture was not granulated, but pressed immediately after drying using a MANESTY industrial press.

suspension concentrate from stage 1 (equivalent to 40 parts of the active ingredient) - 62.50
KOLLIDON CL (disintegrating agent) - 24.25
elcema p100 (binder) - 30.60
EMPICOL LZ (wetting agent) - 2.0
SIPERNAT 22S (Flow Agent) - 0.50
magnesium stearate - 0.10
The tablets were evaluated by dispersing them in water at a rate of 1 tablet weighing 2.5 g (1 g of active ingredient) per 5 l of water, i.e. 0.2 g of active ingredient per 1 liter of water. The solubility of deltamethrin in water at 20 ^o C is less than 2 micrograms / l of water. The tablets were destroyed in 30 seconds.

 Tests for the ability to form a suspension show that after 30 minutes in normal hard water containing 340 ppm calcium in the form of calcium carbonate, 65% of the active ingredient was still in suspension.

Example 4
Stage 1

A suspension concentrate having the composition indicated below was prepared and crushed as described in example 1:
technical atrazine (purity 98%) - 50.0
TERIC 200 - 2.5
SILCOLAPSE 5000A - 0.1
water - 47.4
Stage 2

Using the methodology described in example 1, tablets were prepared, the composition of which is indicated below:
suspension concentrate from stage 1 (equivalent to 36.45 parts of the active ingredient) - 74.4
KOLLIDON CL - 27.9
ELCEMA P100 - 28.4
EMPICOL LZ - 4.0
SIPERNAT 22S - 0.5
magnesium stearate - 0.1
Tablets, each with a diameter of 20 mm and weighing 3.5 g, were obtained by compression at a pressure of 50 atm, using a laboratory precision press. The obtained tablets were tested for hardness, subjecting individual tablets to an increasing load on the edge of the sample. The tablets withstood pressures of up to 5 kg. The decay time was determined by placing a separate tablet in approximately 2 L of water at room temperature and slightly mixing. The test tablet was completely destroyed in 30 seconds. An examination of the suspension obtained under a microscope showed that most of the particles in the suspension had a size in the range of 1-3 microns.

Example 5
Tablets weighing 2.5 g were prepared by homogeneous mixing of the components indicated below and pressing at a pressure of 1.5 tons of the resulting mixture.

technical deltamethrin - 40.0
EMPICOL LZ (wetting agent) - 2.0
TAMOL NNO (Dispersing Agent) - 5.0
KOLLIDON CL (disintegrating agent) - 25.0
ELCEMA P100 (Binder) - 27.4
SIPERNAT 22S (Flow Agent) - 0.5
magnesium stearate (lubricant) - 0.1
Prior to mixing with other components, the deltamethrin is subjected to dry grinding to obtain particles of deltamethrin, the average size of which would be less than 5 microns. For example, it can be in micronized form, like deltamethrin, manufactured by Roussel Uclaf, in which 50% of the particles (by weight) have a size of less than 2 microns. Alternatively, the suspension concentrate from Example 3 can be spray dried and the resulting powder mixed with the remaining ingredients as described above.

 When the tablets were placed in water (1 tablet per 5 liters of water), they were destroyed in 1 minute. Microscopic examination showed that most of the particles in the suspension were about 2 microns in size.

 Applicants have found that when using active pesticides that require very low doses, usually of the order of several grams per hectare, it is extremely desirable to use very fine particles of pesticides, usually having an average size of less than 5 microns, dispersed in the prescribed form for effective, correct and uniform distribution of pesticides. liquid carrier, usually in water. Moreover, the smaller the particle size, the larger the surface area that promotes the release of the pesticide after application to a locus or substrate. However, until now, there has been a problem with the application of pesticides in the form of tablets, since the presence of too small particles of the pesticide leads to an unsatisfactory dispersion rate of the tablet in a liquid carrier. However, it was unexpectedly found that it is possible to obtain high rates of tablet disintegration and dispersion using the method and dosage agent of the present invention, in which the average particle size is less than 5 microns, and usually about 1-3 microns. Moreover, the resulting tablets have sufficient strength, which allows you to work with them in the field, and when dispersed, the tablets have excellent suspension properties.

 Therefore, the dosage agent of the present invention provides a good carrier for such pesticides, since they are compact and therefore easy to transport and store, and they are in a form in which they are safe to work with. Moreover, there is no problem when using large pesticide containers. In addition, they (pesticides) are easy to disperse and apply efficiently and accurately, as previously stated here, i.e. with little loss. Moreover, it was unexpectedly found that after dispersing the tablets in water, the average particle size of the active ingredient was the desired size of 1 to 3 microns, despite the fact that after the active ingredient was ground to particles smaller than 5 microns, it was then pressed with a disintegrating agent into tablets, as a result of which we would expect agglomeration into large particles. However, as further stated, it was unexpectedly found that in the resulting suspensions, the average particle size of the active ingredient was still in the range of 1 to 3 microns.

 None of the known technical solutions does not solve the problems that the applicant managed to exclude in the proposed invention.

 Thus, in European patent EP 0235875 solid formulations are described, for example, granules or tablets consisting of a pesticide and a foaming active disintegrating agent, intended for use by distributing a solid product directly in a mass of water and dispersing it over its surface to suppress those living in water of harmful insects or aquatic plants that infect water bodies. Disintegration of the tablets by foaming provides buoyancy and promotes the distribution of the pesticide on the surface (at the location of harmful insects and floating plants, thereby reducing its dilution in a mass of water. From what has been said, it can be seen that the invention according to EP 0235875 relates to a completely different technical problem than one that is solved by the present invention.

GB 2139893 differs significantly from the present invention in the method for producing compression of mixtures from which tablet formulations can be formed. Two methods described in the British patent are as follows:
(1) The pesticidally active ingredient is dissolved in a small volume of an organic solvent, such as methylene chloride, and an emulsifier or dispersant is added to the solution. This solution is then added to a dry powder mixture of other ingredients, including a disintegrating agent, after which the product is granulated and dried before compression into tablets.

 (2) The pesticidal active ingredient is transferred to a water or oil based suspension concentrate (including an emulsifier or dispersant), the concentrate is added to a dry powder mixture of other ingredients including a disintegrant, after which the product is granulated and dried before compression into tablets.

 The disadvantage of the tablets obtained in this way is that they contain pesticide particles having a wide range of particle sizes due to crystallization or agglomeration during the mixing and drying steps. This means that when tablets are introduced into water to obtain a dispensable formulation, the pesticide particles do not behave the same and the entire product is on a smaller surface area than is desirable for optimal pesticidal activity.

 On the other hand, the method of the present application provides for obtaining particles with a uniform size range, which is achieved due to the additional stage of dry or wet grinding of the particles before mixing and pressing into tablets.

 Pressed formulations according to the patent of Germany 2531426 are not related to this problem and are intended for slow disintegration in a stream of water, while the tablets of the present application disintegrate quickly.

 Thus, the applicants believe that the application offers a fundamentally new technical solution that has an inventive step when compared with known methods.

 In particular, the German patent teaches a solid tablet or granule having a form, containing a pesticide and a disintegrating agent, which should be placed in a stream of water flowing through the pipe so that the pesticide is slowly introduced into the water when the granules or tablets are gradually dissolved. Since the rate of disintegration should be relatively low, the disintegrating agents are selected from vegetable starches, and in particular, may be corn starch.

 The aim of the present invention is to obtain dosage forms (which can be tablets or granules) that can dissolve quickly and which can then be applied using conventional spraying means, i.e., complete dissolution is achieved in less than one minute to achieve the goal. Thus, the invention involves the use of other disintegrating agents that are different from the disintegrating agents used according to the Federal Republic of Germany patent.

 In addition, the Federal Republic of Germany patent does not indicate the need to grind the pesticide to obtain a powder with a particle size of less than 5 microns before preparing the composition. This is because, according to the FRG patent, the water flow carrying the pesticide is immediately directed to the spray head, and there is no need to keep the aqueous composition stable until sprayed. While in the case according to the present invention, it is important that the suspension obtained by dissolving the dosage agent remains stable for a time sufficient to be applied using a conventional spray device, and this is best achieved in the case of obtaining a composition with an average particle size of less than 5 microns, preferably 1 to 3 microns.

 Another advantage provided by the present invention is that the dosage agent contains a predetermined amount of pesticide, which allows a suspension with a pesticide of the desired strength to be obtained simply by introducing the dosage agent into a predetermined volume of water. This is a simple method that eliminates the need to weigh the pesticide and calibrate the equipment, as well as the possibility of accidental environmental pollution, since the proposed dosing agents are easy to manipulate, and they can be easily restored if they fall to the ground, unlike liquid or powder agents.

 The system described in the aforementioned Federal Republic of Germany patent does not make it possible to control the concentration of the composition, since this depends on the flow rate of water per hard tablet, water temperature, and other factors.

It should be noted that the essence of the present invention is not associated with the chemical nature of the active ingredients, in is associated only with their physical characteristics. That is, the active ingredients must be solid at 25 ^o C (that is, must have a melting point above 25 ^o C), must be poorly soluble in water and must be crushed to particles less than 5 microns in size. Provided that the active ingredients have such characteristics, they fall within the scope of the present invention.

 Thus, the present invention can be applied to any products having such physical characteristics.

Claims (6)

1. A pesticidal dosage form in the form of a single compressed form, comprising the active ingredient, solid at 25 ^o C, poorly soluble in water, a disintegrating agent based on polyvinylpyrrolidone, a dispersant, a wetting agent and additional substances that can decompose when added to a sufficient amount of water to form suspension of pesticide, characterized in that it contains 5 to 60 parts by weight pesticide with a particle size of less than 5 microns and 25 to 50 wt.h. polyvinylpyrrolidone.  2. The pesticidal agent according to claim 1, characterized in that it forms a suspension with an average particle size of the pesticide 1-3 microns. 3. The pesticidal agent according to claims 1 and 2, characterized in that it includes a pesticide with a solubility in water of less than 1000 mg / l at 25 ^o C.  4. The pesticidal agent according to claims 1 to 3, characterized in that it contains a pesticide selected from the group consisting of atrazine, deltamethrin, thiophanate-methyl, hexaconazole, and crosslinked polyvinylpyrrolidone as polyvinylpyrrolidone.  5. The pesticidal agent according to paragraphs. 1 to 4, characterized in that the additional substances are selected from the group comprising a lubricating, anti-foaming binder, fluidity improver, filler.  6. The pesticidal agent according to claims 1 to 5, characterized in that it is capable of disintegrating in water with the formation of a suspension over a period of time not exceeding 1 minute.