JP2001151603A - Coated preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a preparation containing water-soluble chemical having effects such as repellency, attraction or killing of creatures such as noxious insects and capable of controlling releasing in water or soil. SOLUTION: This coated preparation is characterized by having a configuration of covering a molding material composed of water-soluble chemical and water-insoluble plasticizer and an inorganic material with a material mixed a water-soluble, water-swelling or water-absorptive material with a water- insoluble material.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to an organism which harms crops, which inhibits reproduction by repelling action, repelling action,
The present invention relates to a pesticide formulation containing a water-soluble drug capable of protecting agricultural crops by killing action, wherein the release rate of the water-soluble drug is constant and most of the contained drug can be eluted. The present invention also relates to a pesticide formulation that can be composed of only a substance having no harmful effect on the environment.

[0002]

2. Description of the Related Art In addition to those pesticides that have been developed with the intention of killing target organisms, they also have the effect of simply repelling organisms (repellent action) to protect agricultural crops from predation by organisms. Some have. The latter has a repellent effect on specific organisms, has little effect on other biological systems, and can be said to be an environmentally friendly pesticide.

On the other hand, there are also pesticides that release a substance having a function of attracting an organism (attracting action) to protect the organism from the effects of the organism on crops. For example, intentional release of insect pheromones released by females of the same species can disrupt male olfaction and make it impossible to locate females, thereby suppressing mating reproduction. You can do it.

[0004] A solid material as a base material impregnated with a substance having such a killing, repelling, and attracting action is left, sprayed, and fixed in the vicinity of the agricultural crop, thereby obtaining
As a result, the crop can be protected from biological damage.

[0005] However, in recent years, it has been an important issue in practical and functional aspects to gradually and stably release and volatilize volatile substances of pesticides in a target place for a long period of time.

[0006] For example, water-soluble pesticides are released from their parts when the pesticide components eluted by water from the inside of the preparation are absorbed by the roots of the plant and reach stems, leaves, flowers, etc., and as a result, It acts to repel (repellent) or exterminate (killing) or attract (attractive) the following organisms.

[0007] When substances having these effects are used in water or fields, there is a concern about environmental pollution from the viewpoint of soil pollution. The excessively provided drug is carried by water without being absorbed by plants and the like, and is eventually diffused widely by groundwater. In turn, these chemicals have a negative impact on the environment.

Therefore, in order to solve these problems,
If the elution amount of the chemical contained in the pesticide is provided in a controlled form, the influence on the environment can be greatly reduced. This will be recognized as an important issue in the future of agricultural production, given the increasing awareness of the environment in the near future.

[0009] To this end, various measures have been taken to slow the rate of dissolution of the pesticide. JP-A-49-
No. 1731, the surface of a granular material containing the first pesticide component is coated with a waxy material also containing the second pesticide component, or the surface of the granular material is coated with a waxy material, It discloses that the second component is supported on a coating layer of the waxy substance.
However, Japanese Patent Application Laid-Open No. 49-1731 describes the mortality of the pesticide and the residual ratio of the active ingredient, but does not disclose the details of the release characteristics. Not.

Japanese Patent Application Laid-Open No. 54-92222 discloses a coating material using a lipophilic material which is solid at normal temperature as a coating material in order to provide a delayed effect. JP-A-55-62002 uses whale wax and paraffin as a coating material.

[0011] Further, there is disclosed a material using a biodegradable polymer as a coating material as an environment-friendly material.

[0012] However, none of these uses water-soluble agricultural chemicals and controls the elution amount at low cost and highly. Under the circumstances, there is a demand for the development of a preparation whose dissolution characteristics are highly controlled at low cost.

[0013]

An object of the present invention is to control a water-soluble drug having a killing, repelling and attracting action at a constant elution rate. Further, in controlling the elution method, it is also a problem to be solved by the present invention that the constituent material is made of a material having no or little effect on the environment. .

[0014]

Means for Solving the Problems The present inventors have found out the structure and the composition ratio of a preparation which can make the dissolution rate of a water-soluble drug constant, which can be obtained only by materials having little effect on the environment. .

That is, the present invention relates to (1) a preparation containing a solid water-soluble drug having an attracting, repelling or killing effect on living organisms, the drug being sparingly soluble in water and containing the water-soluble drug. A plastic material 1 made of a substance that is incompatible with or low in compatibility with each other, an inorganic material 2, and a core material containing the water-soluble drug are hardly soluble in water and low in compatibility with the water-soluble drug. A coated preparation comprising a material 4 and a composite material 6 having a structure in which a material 5 which is soluble, swellable or water-absorbable in water is mutually dispersed; The solubility of the drug in water is 2
It is 1 g / L or more and 100 g / L or less at 5 ° C (1)
(3) In the volume of the portion covered by the composite material 6, the ratio of the volume occupied by the water-soluble drug to the portion excluding the volume occupied by the plastic material 1 and the inorganic material 2 is 80% or more. A coated preparation according to (1).

[0016]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention comprises a component having low solubility in water of a water-soluble drug having an attracting, repelling or killing effect on living organisms, including a component which is soluble, water-absorbing or swellable. A long-acting dissolution preparation characterized by being coated with a material, and having a linear dissolution mechanism in which the dissolution amount per day is constant during the number of days required for dissolution. FIG. 1 shows the basic structure of the preparation of the present invention. The preparation of the present invention comprises a plastic material 1 and an inorganic material 2 made of a substance that is sparingly soluble in water and is incompatible or incompatible with a water-soluble drug (hereinafter, the plastic material 1 and the inorganic material 2 are combined together). And a molding material 3), a core material containing a water-soluble drug is mixed with a material 4 that is hardly soluble in water and has low compatibility with the water-soluble drug, This is a coating preparation obtained by coating a composite material 6 having a structure in which a material 5 having water absorbency and a material 5 having water absorption properties are mutually dispersed.

The water-soluble drug used in the present invention is selected to have a killing action, a repelling action, or an attracting action on an organism. It is desirable that the solubility of the water-soluble drug in water is sufficiently high. This is because the drugs targeted by the present invention are limited to those that are absorbed together with water from plant roots. It is a preferable condition that the solubility in water is 1 g / L or more at 25 ° C. More preferably, it is 5 g / L or more, most preferably,
10 g / L or more. Preferred conditions for the upper limit of the solubility in water are 100 g / L or less, and more preferably 75 / L or less. Hereinafter, the solubility in water is replaced with the solubility in water, and the amount of the water-soluble drug dissolved in 100 cc of water is expressed by volume.
Calculate by cc and display by%.

The water-soluble drug used in the present invention includes:
Fruit trees such as apple, chestnut, persimmon, grape, peach, tangerine, tea, cherry, camellia, rose, etc. Specialty crops such as wasabi, strawberries,
It has an effect or an action on vegetables such as chopsticks, spinach, tomato, and cucumbers, and on organisms that harm the leaves and roots, or fruits and fruits.

Of course, those that give an effect or action to organisms that give water plants or moss for appreciation are also effective.

Further, those having a killing effect include trevon, DDPV, PHC, DEP, MPP,
MEP agents, PHC agents, or substances such as dianodine, isoxathion, prothiophos, phenothrin, permethrin and the like.

Further, as a repellent, for example, as an egg-laying repellent against tobacco beetle,
3-dihydro-3,5-dimethyl-2-ethyl-6
(1-methyl-2-oxobutyl) -4H-vilan-4
Although -ON is disclosed in JP-A-1-132501, these may be used. In addition, dimethyldichlorovinyl phosphate or the like is used. Trebon also has a repellent effect.

Further, as an attractant, a typical one using a sex pheromone is used.
Many pheromone components have been identified and manufactured. The target is a lot of insects, such as moths, butterflies, chafers, beetles and the like. For example, isopentylamine-β-methylbutane and the like can be mentioned.

Further, stabilizers for preventing deterioration of the water-soluble drug, various elastomers (SBR, NBR, SBS
Type ternary block copolymer thermoplastic elastomer), pigment, dye, antistatic agent, ultraviolet absorber, antioxidant, flame retardant, release agent, lubricant, thickener and diluent according to the purpose.
And it can be suitably used within a range not to impair the effects of the present invention.

As the plastic material 1 used in the present invention, which is made of a substance which is hardly water-soluble in water and is incompatible with or incompatible with a water-soluble drug, a biodegradable material is preferable, and wax or biodegradable material is preferred. A polymer is used. Of the waxes, natural waxes include plant-based natural wax, animal-based natural wax, and mineral-based natural wax. this house,
Typical examples of the plant-based natural wax include candelilla wax, carnauba wax, rice wax, wood wax, and jojoba oil. And beeswax, lanolin, and whale wax are typical examples of animal-based natural waxes. Examples of mineral natural wax include montan wax, ozokerite, and ceresin. Furthermore, petroleum waxes include paraffin wax, micro wax and the like. These waxes are decomposed during long-term standing in a natural environment, and consequently lose their shape, and have biodegradability. In this sense, it can be said that the material does not adversely affect the environment. Examples of biodegradable polymers include polyglycolic acid, polylactic acid, polyhydroxybutyric acid, polycaprolactone, and aliphatic polyester 3-
Hydroxybutyrate, 3-hydroxyvalerate, 3
Polymers such as -hydroxycaprolate and copolymers thereof. Furthermore, examples of the polyalkylene glycolic acid include polyethylene glycol (hereinafter abbreviated as “PEG”), polypropylene glycol, polybutylene glycol, and the like. These additives may be used alone or as a mixture of two or more, but it is a necessary requirement for the plastic material in the present invention that it is not water-soluble, and the molecular weight for that purpose is 200.
It is desirably 0 or more.

The plastic material 1 may be of one kind, but may be composed of a plurality of substances. The requirement for this material is that it be incompatible with the selected water-soluble drug, which must be a poorly compatible combination with each other.

When the water-soluble drug is soluble in the plastic material,
In many cases, good drug dissolution characteristics cannot be obtained. This is because, by dissolving in a plastic material that is hardly soluble in water, the opportunity to come into contact with water is lost, and as a result, components of a water-soluble drug that dissolves in water and cannot be dissolved come out. . In addition, even if the water-soluble drug does not dissolve in the poorly soluble plastic material, the component coated with the water-soluble drug by the poorly soluble material also loses the opportunity to come into contact with water. Residual components that cannot be dissolved and dissolved in water are generated. It is also an important requirement that no reaction occurs between the water-soluble drug and the poorly soluble plastic material 1.

The preferred content of the plastic material 1 in the molding material 3 is 5 to 90% by volume, more preferably 1 to 90% by volume.
0 to 80% by volume.

Specific examples of the inorganic material 2 used in the present invention include, for example, talc, kaolinite, SiO ₂ ,
Clays and the like may be mentioned, and more specifically, when the purpose is to improve the physical properties of blocking resistance, a material having a small particle size, which is favorably dispersed without aggregation when melt-kneaded with a resin is preferably used. Can be The content is not particularly limited, but is preferably 10 to 95% by volume in the molding material 3 in the preparation. More preferably, the content is 20 to 90% by volume.

The molding material 3 mixed with these water-soluble drugs and formed by mixing and molding the plastic material 1 and the inorganic material 2 constituting the core material of the preparation is free of water that has penetrated through the coating material layer. It is also important to have a structure that can move. For this purpose, it is necessary that other materials of the water-soluble drug have little influence on breaking down the structure of the water-soluble drug by intrusion of water.

In the case where the water-soluble drug, the plastic material 1 and the inorganic material 2 are mixed at an appropriate ratio, the water-soluble drug and the plastic material 1 are mixed with each other, so that the plastic material hinders the mixture. Water-soluble drugs do not lose their chance of contact with water. The inorganic material 2 is also an important constituent material, and its presence and mechanical mixing at the same time prevent the water-soluble drug from being covered by the plastic material 1. This is because even if the water-soluble drug is coated with the plastic material during the mixing process, the inorganic material cuts the coated portion, thereby preventing the formation of a fine coated structure.

The form of the preparation may take various forms. Various forms such as a spherical type, a cylindrical type, a pellet type, a rectangular parallelepiped type, a disk type, and a string type can be given. Structurally, the water-soluble drug as the core material, the plastic material 1 and the inorganic material 2 are composed of a water-soluble, water-absorbing or swelling component in the water-soluble or extremely low-solubility component of the coating film. What is necessary is just to have the structure covered with the material containing.

It is an important requirement that the core is completely covered with the coating film. Also in this respect, the shape is not a big problem.

The size of the core material formed of the forming material varies depending on the method of use, and the appropriate shape also differs, but it is taken into consideration that the water-soluble drug is released by diffusion. Then there is an appropriate size. That is, the appropriate size as the representative diameter is 0.
It is 3 mm or more and 30 mm or less, preferably 0.4 mm or more and 10 mm or less, and more preferably 0.5 mm or more and 5 mm or less. The length of the string-shaped object is not limited, and can be freely set.

The representative diameter mentioned here is the diameter in the case of a sphere or a cylinder, and the length of one side in the case of a rectangular parallelepiped or the like.

The thickness of the coating film is appropriately determined according to the desired release characteristics, but the general thickness is 1/20 of the representative diameter of the core material previously given.
It is desirably in the range of up to twice. If the thickness is smaller than this range, a problem occurs in the strength of the coating film, and not only unnecessary elution is likely to occur, but also sufficient elution suppression cannot be provided. On the other hand, when it is thick, the effect of suppressing elution is increased, and the target water-soluble solvent contained therein may remain.

It is necessary that the material 4 used in the present invention is a material that is hardly soluble in water and has low compatibility with water-soluble drugs. As a material for that purpose, a material substantially equivalent to the molding material 3 can sufficiently achieve the purpose. That is, a biodegradable wax or a biodegradable polymer is suitable. Of the waxes, natural waxes include plant-based natural wax, animal-based natural wax,
There are mineral natural waxes. Of these, candelilla wax, carnauba wax, rice wax, wood wax, and jojoba oil are typically used as plant-based natural waxes. And beeswax, lanolin, and whale wax are typical examples of animal-based natural waxes. As mineral natural wax, montan wax,
There are ozokerite and ceresin. Furthermore, petroleum waxes include paraffin wax, micro wax and the like. These waxes are decomposed during long-term standing in a natural environment, and consequently lose their shape, and have biodegradability. In this sense, it can be said that the material does not adversely affect the environment. Examples of the biodegradable polymer include polyglycolic acid, polylactic acid, polyhydroxybutyric acid, polycaprolactone, and aliphatic polyesters such as 3-hydroxybutyrate, 3-hydroxyvalerate, and 3-hydroxycaprolate. Molecules and copolymers thereof. Furthermore, examples of the polyalkylene glycolic acid include polyethylene glycol (hereinafter abbreviated as “PEG”), polypropylene glycol, polybutylene glycol, and the like. These additives may be used alone or as a mixture of two or more, but it is a necessary requirement for the plastic material in the present invention that it is not water-soluble, and the molecular weight for that purpose is 2,000. It is desirable to have the above. Further, an inorganic material may be used. Specific examples of such materials include, for example, talc, kaolinite, SiO ₂ , clay, and the like. What melt | dissolves and knead | aggregates well when melt-kneaded is used suitably. That is, these mixtures are suitable for the coating film material 4
It becomes a suitable material.

As the material 5 having solubility, swelling property, or water absorption in water, any material having the property can be used. Among those things,
There is a kaolilite type contained in clay. Although clay itself is an inorganic substance, it contains a water-absorbing material such as kaolin, and a water-absorbing material such as kaolin is preferable. The proportion of the water-absorbing material such as kaolin in the coating film is preferably between 5 and 15%. More preferably, it is 7 to 12%.

The linear elution characteristics of the water-soluble drug provided by the present invention can be explained as follows. That is, intrusion of water from the outside is an indispensable requirement in releasing a water-soluble drug. The drug dissolves in the water that has entered from the outside and diffuses through the water to be released to the outside.
Now, in order to obtain the elution characteristic of linear elution, it is necessary to consider that a two-stage mechanism works in the elution. That is, a stage of suppression at the beginning of elution and a stage of elution at a constant rate. By appropriately adjusting these two steps, linear elution can be achieved.

The initial stage of suppression in elution is the stage of blocking by coating. If there is no coating and the structure allows the water-soluble drug to easily come into contact with external water, it is easily expected that the water-soluble drug will elute quickly in the initial stage. In order to prevent this rapid elution, it is essential to have a function capable of suppressing intrusion of water from the outside. However, if the penetration of water is completely suppressed, the elution of the water-soluble drug is also completely suppressed, and the function as a preparation cannot be achieved. Therefore, it is necessary to achieve a moderately controlled water intrusion rate early in the elution.

In the second stage, it is important that the coating film has a performance of appropriately suppressing the passage speed of the water-soluble drug in a state where the water is sufficiently contained. in this case,
If the concentration difference inside and outside the coating film is constant,
The elution rate is determined by the rate uniquely determined by the diffusion coefficient. This is because the driving force for determining the diffusion speed is constant. Therefore, if a water-soluble drug having an appropriate solubility is dissolved by water entering from the surrounding environment and the concentration of the water-soluble drug is constant, the concentration of the water-soluble drug outside the membrane is almost equal to zero. Therefore, the diffusion rate from the inside to the outside of the coating film should be constant.

This constant elution speed has a constant speed because the driving force is constant as long as the concentration of the water-soluble drug in the coating film is constant. The case where this concentration is constant is a case where the water-soluble drug inside the coating film maintains the saturated concentration. In other words, when the solubility of the water-soluble drug in the core material in water is high and the proportion of the hardly water-soluble material in the core material is large, a small amount of the water-soluble drug dissolves in water, so that it is easily saturated. Since the concentration can be reached, a sufficiently high constant diffusion rate and a constant elution rate are obtained.

What matters is the occupancy of the water-soluble drug in the volume of the coating film in the preparation. Since the water-soluble drug itself has solubility, when the water-soluble drug is contained in the coating film in a large amount and has a content exceeding the saturation concentration, the water-soluble drug is precipitated without being dissolved. It is in a state. In this state, when the drug is eluted through the coating film, it is used to replenish the undissolved water-soluble drug as it dissolves out. Will be shown.

In view of the above problem, FIG. 2 shows the volume ratio of the water-soluble drug in the coating film. The horizontal axis represents the volume ratio (X1) of the molding material in the volume of the coating film (the volume of the core material coated with the composite material 6), and the vertical axis represents the volume ratio of the water-soluble drug in the volume of the coating film. (Y1)
It is shown.

In FIG. 2, a thin oblique straight line is a line indicating a volume ratio obtained by subtracting the volume ratio of the molding material in the coating film volume from the coating film volume. That is, 100
A thin straight line indicates -X1 (%). The thick line is a line indicating the volume ratio of the water-soluble drug contained in the coating film volume, and the region sandwiched between the thick line and the thin line is the water-soluble drug even if the molding material occupies the coating film. However, it shows the portion which is not, that is, the void ratio. In other words, this figure shows the ratio of the water-soluble drug and the void in the coating film. The thick line indicates the volume ratio occupied by the water-soluble drug, and is a value that can be read as Y1 on the vertical axis. That is, X1 + Y1 + (gap ratio) = 100 (%).

Further, the thick broken line indicates the solubility of the water-soluble drug in water, and the point at which X1 = 0% intersects with the Y axis indicates the saturated solubility of the water-soluble drug. Also,
The thick dashed line is called the solubility curve.

The portion showing the linear type elution is a portion between the content curve and the solubility curve, and is shown as a linear elution portion in the figure. That is, X contained in the core material
When the core material contains a water-soluble drug having a content exceeding the solubility curve with respect to 1 (volume ratio of the molding material in the volume of the coating film), the intersection of the solubility curve and the content curve of the perpendicular line at X1 The point between the two points is where the linear elution takes place.

When the linear elution portion is small, that is, when the content curve is at a low position, the ratio of the water-soluble drug to be eluted in the linear type is also small, and as a result, the linear preparation is obtained. It will not be able to show its effect.

Therefore, the condition for the preparation provided by the present invention to exhibit a sufficient linear type elution is that the water content to the part excluding the volume occupied by the molding material 3 in the internal volume covered by the composite material 6 It is necessary that the volume ratio of the sex drug is sufficiently high. The volume ratio required for this is 80% or more, and more preferably 90% or more.

In manufacturing the preparation of the present invention, first, a core material is manufactured. A method of mixing and stirring the plastic material 1 and the inorganic material 2 and mixing a water-soluble drug may be used, or a method of mixing and stirring the plastic material 1 and the inorganic material 2 and mixing a water-soluble drug may be used. Regarding the temperature condition at the time of stirring, it is not preferable to perform the stirring at a temperature at which both the water-soluble drug and the plastic material exceed the melting point. It is important that the temperature be lower than the melting point of either material.

The core material containing the water-soluble drug formed by mixing must be adjusted to an appropriate size. For example, a tube formed by extruding through a die hole having a diameter of about 2 mm after stirring may be cut into an appropriate size using a chopper.

Further, the step of coating the core material will be described. As a method of coating molding, rolling together with the coating material at a temperature close to the melting point, or putting it in the coating material and stirring at a lower temperature condition than when forming the molding material And the like. These operations make it possible to produce the formulation disclosed in the present invention.

[0052]

Embodiments of the present invention will be described below in detail.

Example 1 A formulation was formed using MTI-446 represented by the following formula (1) as a water-soluble pesticide. MTI
-446 has a killing effect, and has an effect of absorbing organisms that are harmful to the plant by being absorbed from the roots of the plant and reaching the leaves and stems.

[0054]

Embedded image

This MTI-446 (weight fraction 2.4%), acid montan wax (trade name LUWAX-S) (weight fraction 15%), calcium carbonate (weight fraction 67.6%), white carbon (weight fraction) 5%) and S talc (10% by weight) to form a molding material 3. In this case, MTI-446 itself is a water-soluble solvent, and montan wax is the plastic material 1. The content ratio of the plastic material in Example 1 is 15%. Then, calcium carbonate, white carbon and S talc correspond to the granular inorganic material 2, and the content volume ratio is 82.6%. A material formed by mixing these is the molding material 3 containing a water-soluble drug.

This molding material is further mixed in a mixing and stirring tank.
After stirring for a sufficiently long time of 0 minutes or more, the diameter 2
The material extruded from a die hole of about mm and formed into a tube shape is cut into a length of 2 mm to 4 mm using a chopper to produce a core material.

The solubility of MTI-446 in water is 40 g / L at 25 ° C. Therefore, when expressed by the dissolution rate used in the present invention, it is 4%. Therefore, the solubility is located in the lower range than the solubility curve shown in FIG. On the other hand, the weight ratio of the material shown in the molding material 3 other than the MTI-446 to the inner volume of the coating film is 97.6%. Since the mixing specific gravity of the molding material is about 2 and the specific gravity of MTI-446 is 1, X1 is 95.3% as a result.
And the ratio of MTI-446 itself to the volume in the coating film is:
It was 4.5%. When water invades this volume, MTI-446 in excess of solubility remains and forms a saturated concentration, but only 4% dissolved, leaving the remaining "MTI-446 and void fraction MTI-44 is used for the 92% volume ratio of “4.7% of the volume ratio in the coating film volume”.
6 will remain. Therefore, in the portion showing linear elution, 92% of MTI-446 contributes to elution showing linear elution.

Next, a coating film was formed on the molding material. The materials used to form the coating film were paraffin wax and clay, and Hubasami clay A-300 was used as the clay. The general composition of this clay is 50-55% quartz and 3% pyrophyllite.
0-35% and kaolin 10-15%. Of these substances, the only component that absorbs water is kaolin.

The method for producing these coating films is as follows.
This is carried out by maintaining the temperature at 0 ° C. and sufficiently stirring under normal pressure. In a prototype production at a laboratory level, a conical flask is stirred in a thermostat kept at 80 ° C. with a spatula. The stirring time was 20 to 30 minutes. In addition, the paraffin wax and the clay were sequentially added little by little, and a strong coating film could be formed by well shaking the Erlenmeyer flask.

The ratio of paraffin wax and clay used for coating is 25% and 75%, respectively. In this case, the ratio of the water-absorbing kaolin in the composite material to be the coating film is 7 to 11%.

The formulation prototype with the formed coating film was
g was placed in 1 liter of ion-exchanged water at 25 ° C. and allowed to stand. And the first day, the third day, the seventh day, the fourteenth day,
Day 0 water was collected and the concentration of the water was measured by liquid chromatography.

FIG. 3 shows the obtained data on the elution characteristics.
The dissolution rate reaches 90% on day 30, and since the first day the increase in dissolution rate is almost linear. Therefore, this prototype preparation exhibited the target linear dissolution characteristics.

Comparative Example 1 In Comparative Example 1, the case where only the core material was formed and the covering film was not formed was examined.

As a water-soluble pesticide, MT was used in the same manner as in Example 1.
A formulation was formed using I-446. This MTI-446 (weight fraction
2.4%) and acid-based montan wax (brand name LUWAX-S)
(Weight fraction 15%) and calcium carbonate (weight fraction 67.6%),
White carbon (weight fraction 5%), S talc (weight fraction 1
0%) to form a molding material. In this case, MTI-446
The material itself is a water-soluble solvent, montan wax corresponds to the plastic material 1, and calcium carbonate, white carbon and S-talc correspond to the inorganic material 2. The material formed by mixing these is the molding material 3.

This molding material was stirred in a mixing and stirring tank for a sufficiently long time of 30 minutes or more in the same manner as in Example 1, and then extruded from a die hole having a diameter of about 2 mm to form a tube. , 2mm to 4mm long using a chopper
Cut into pieces.

10 g of the thus-prepared preparation without a coating film was placed in 1 liter of ion-exchanged water at 25 ° C., and allowed to stand. And the first day, the third day, the seventh day,
Water was collected on days 14 and 30, and the concentration of the water was measured by liquid chromatography.

FIG. 4 shows the obtained data on the elution characteristics.
The dissolution rate reached 90% on the first day and reached 100% on the third day. It could be determined that this preparation could not control the dissolution rate of the water-soluble drug contained therein at all. However, the entire amount of the water-soluble drug could be eluted.

(Comparative Example 2) In Comparative Example 2, a trial product was prepared in which only a core material was formed and a coating film was not formed. As a wax, an ester-based montan wax (trade name LUWAX-E) was used. (Weight fraction 15%) was used in place of the acid-based montan wax (trade name LUWAX-S). Other manufacturing procedures are exactly the same as in Comparative Example 1.

10 g of the thus-prepared preparation without a coating film was placed in 1 liter of ion-exchanged water at 25 ° C., and allowed to stand. And the first day, the third day, the seventh day,
Water was collected on days 14 and 30, and the concentration of the water was measured by liquid chromatography.

FIG. 5 shows the obtained elution characteristics data.
The elution rate reached 50% on day 5 and 60% on day 15. However, after that, the elution did not progress very much, and as a result, even after 30 days, 3
It was confirmed that 0% or more of the water-soluble drug remained contained in the preparation.

When such a wax, which cannot dissolve the entire amount of the drug, is used in combination with the water-soluble drug, it can be confirmed that the water-soluble drug itself remains incorporated in the preparation.

It can be seen that the formation of the coating film as described above is an essential requirement for exhibiting linear elution characteristics.

As described above, the preparation of the present invention can minimize its effect on the sustainability and the global environment, and at the same time, the materials used are inexpensive. It can be downed and is extremely valuable industrially.

[Brief description of the drawings]

FIG. 1 is a diagram showing the basic constitution of the preparation of the present invention.

FIG. 2 is a diagram showing the proportion of a water-soluble drug that gives linear dissolution characteristics according to the present invention.

FIG. 3 shows the results of dissolution characteristics of the coated preparation shown in Example 1.

FIG. 4 shows the results of dissolution characteristics of the uncoated preparation shown in Comparative Example 1.

FIG. 5 shows the results of dissolution characteristics of the uncoated preparation shown in Comparative Example 2.

Continuing from the front page (72) Inventor Koichi Nagashima 1144 Togo, Mobara-shi, Chiba F-term (reference) 4H011 AC02 AC06 AC07 AC07 BB03 BB11 BB15 BB17 BC03 BC06 BC18 BC19 DA04 DD04 DF02 DG03 DG04 DG05 DH03 DH13 DH25 DH25DH26

Claims (3)

[Claims] 1. A preparation for retaining a solid water-soluble drug having an attracting, repelling or killing effect on living organisms, which is poorly soluble in water and incompatible with the water-soluble drug, or Plastic material 1 made of a substance with low compatibility
And an inorganic material 2 and a core material containing the water-soluble drug,
Material 4 that is poorly soluble in water and has low compatibility with the water-soluble drug
And a material 5 having solubility, swelling, or water absorption in water, coated with a composite material 6 having a mutually dispersed structure. 2. The water-soluble drug has a solubility in water of 25.
The amount is 1 g / L or more and 100 g / L or less at 0 ° C.
3. The coated preparation according to item 1. 3. The ratio of the volume of the water-soluble drug to the portion excluding the volume occupied by the plastic material 1 and the inorganic material 2 in the volume of the portion covered by the composite material 6 is 80%.
The coated preparation according to claim 1, which is the above.