JPH11286402A - Biodegradable sustained-release preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation which has no adverse effects on environments and can control the release rate by blending a specific volatile organic compound which shows volatility at ordinary temperature in the atmosphere and acts on organisms with a base material mainly composed of a biodegradable polymer material. SOLUTION: This preparation is obtained by blending (A) a volatile organic compound (isoxathion, isopentylasmine-'-methylbutane or the like) which has volatility at ordinary temperature in the atmosphere and acts on organisms with (B) a base material mainly composed of a biodegradble polymer material (a polylactic acid, a fatty acid polyester or the like). The radius R of the preparation is given by the equation R=√ D/2.5×10<7> /10<(0.0002/(> F<0.0023))> } from the diffusion coefficient D [cm<2> /sec] and the surface migration rate coefficient F[1/cm] of the above component A in the base material in order to adjust the ratio of the residual concentration of the volatile organic compound after 30 days under the ordinary temperature condition to the initial concentration to 10 wt.% or less.

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,
It relates to a pesticide formulation containing a substance that can protect agricultural crops by killing action, and after a considerable period of time after its use, acts mainly on microorganisms in soil or water to reduce environmental impact. The present invention relates to a biodegradable sustained-release preparation having a function of decomposing into a chemical substance having no harmful effect to the substance and losing its shape.

[0002]

2. Description of the Related Art 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 at a target place for a long time.

[0003] Agrochemicals are generally developed with the intention of killing target organisms.
However, to protect crops from predation by organisms,
Those having an action of simply repelling living things are also effective. These have a repellent effect on specific organisms, have little effect on other biological systems, and can be said to be environmentally friendly pesticides.

[0004] Conversely, there is an object that releases a substance having a function of attracting an organism to protect the organism from the effects of the organism on crops. For example, if the substance releases a sex pheromone for the purpose of inhibiting mating of an organism, the effect of the pheromone cannot confirm the presence of each other, and as a result, it is possible to suppress the reproduction by mating. It is.

[0005] A solid material as a base material is impregnated with these substances having a killing, repelling, and attracting effect, and these are left, sprayed, and fixed in the vicinity of agricultural crops. As a result, the crop can be protected from biological damage.

[0006] Among them, pheromone is used as a substance for attracting organisms, and several methods have been disclosed for immobilizing the pheromone on a substance based on the pheromone to form a preparation.

Among them, a pheromone that is frequently used is one in which a pheromone is sealed in a capillary such as polyethylene or ethylene-vinyl acetate copolymer, and many pheromones are disclosed. For example, JP-A-56-142202, JP-A-57-9705, and JP-A-57-729.
No. 04, JP-A-57-45101, JP-A-5-45101
7-156403, JP-A-59-216802, JP-A-60-215637, and JP-A-61-1.
There are disclosures in, for example, JP-A-202643, which have a function of gradually releasing pheromone. However, the methods disclosed in these methods generally do not allow stable release, or when it is desired to increase the amount of release, it is necessary to increase the length of a thin tube. There was a problem and it was practical.

[0008] Further, as disclosed in JP-A-7-231743, a pheromone preparation based on a synthetic resin compatible with pheromone has been developed. Here, the pheromone evaporation energy is 21,000cal / mole ~
It is stated that it is in the range of 27,000 cal / mole, and here it is considered that the evaporation rate of the pheromone is controlled. However, pesticide preparations formulated with volatile pheromones are mainly sprayed or left on the soil, and after volatilization of the pheromone, the pesticide preparations remain in the soil, so it can be said that consideration for the environment is poor. .

Pheromone preparations based on polymer materials having a biodegradable function have been developed for such preparations having properties remaining after use. JP-A-61-
No. 41321 discloses a pheromone preparation using a biodegradable polymer material as a hollow substrate. This biodegradable polymer material includes polyhydroxy acids such as polylactic acid,
Using poly (α-amino acid) such as polyglutamic acid,
It discloses that an active substance such as a pheromone is used by filling the hollow tube. But,
From such pheromone preparations, no specific guidance for controlling the release rate can be obtained.

Japanese Patent Application Laid-Open No. 4-230602 discloses a pheromone preparation containing 1 to 40% of a polymer material having a biodegradable or photodegradable function or a degradable function comprising a mixture thereof. Have been. However, in this pheromone preparation, even after the degradable polymer is decomposed, non-decomposable components remain, and cannot be said to be a degradable pheromone preparation in a strict sense.

The preparation disclosed in JP-A-5-163110 is a sustained-release pheromone preparation in which a biodegradable condensation product of 3-hydroxybutyric acid and another hydroxyaliphatic sheet is sheeted. In this case, the low release rate was to be solved by reducing its thickness,
There is a disadvantage that the processing step and shape of the pheromone preparation are limited to those for sheets.

[0012] Therefore, a device for improving the release characteristics of pheromone has been devised for a biodegradable polymer material.

JP-A-6-116103 discloses a pheromone preparation based on a biodegradable polymer material. The biodegradable polymer material disclosed in JP-A-6-116103 is a natural polymer such as cellulose, chitin, chitosan, and burlan, or polyvinyl alcohol, polyethylene glycol, polyurethane, polyamide (poly-α-amino acid, etc.). ), Synthetic polymers such as aliphatic polyesters. As a result, the release characteristics of the pheromone were improved, but the release mechanism was not disclosed at all.

Japanese Patent Application Laid-Open No. 9-137049 discloses a polylactic acid, a plasticizer, and a heat stabilizer if necessary.
A sustained-release preparation containing a sex pheromone using a polylactic acid composition containing a release agent is disclosed. The plasticizer is contained in this preparation to provide the mechanical strength and flexibility required for the sustained-release preparation. As the plasticizer, aliphatic dibasic acid ester, phthalate Acid ester, hydroxy polycarboxylic acid ester, polyester plasticizer, fatty acid ester, epoxy plasticizer, ethylene-vinyl acetate copolymer, polyvinyl acetate, polycaprolactone, malonic acid, succinic acid, adipic acid, fumaric acid, etc. Condensed polymers of dicarboxylic acids and ethylene glycol, and diols such as propylene glycol, butanediol, and hexanediol, and condensation polymers of hydroxy acids such as hydroxybutyric acid and hydroxyvaleric acid are preferred. It is stated that the plasticizer may be used alone or as a mixture of two or more. Further, among those used as a mixture of two or more, preferably, di-2-ethylhexyl azelate, di-2-ethylhexyl adipate, and an ethylene content of 20 to 9 are used.
An ethylene-vinyl acetate copolymer (EVA) having 5% and a vinyl acetate content of 5 to 80%, polycaprolactone, a condensation polymer of a dicarboxylic acid and a diol, and a hydroxy acid are used.

[0015]

However, the above publications do not mention a specific method for controlling the emission characteristics of the pheromone. This is Japanese
No. 137049 is no exception, and no method is disclosed about how to control the pheromone emission rate.

In particular, regarding the biodegradable polymer materials, it is difficult to control the release rate of the pharmaceutically active ingredient simply by using them as a base material. For example, it is difficult to control the release characteristics of polylactic acid by simply adding a pheromone to the polylactic acid or simply mixing a plasticizer. This is because polylactic acid has a relatively rigid structure, and is excellent in molding and holding performance by being processed into a string shape, etc., so it is easy to handle, but conversely, it is rigid. Therefore, the pheromone itself is not easily diffused in the polymer, and as a result, good release properties cannot be obtained. Therefore, it must be said that it is difficult to design a material with controlled release properties without clear guidelines.

Furthermore, in order to eliminate the hardly diffusible emission characteristics, it is necessary to adopt a configuration in which the manufacturing method and the molded internal structure are also taken into consideration. However, these facts are not known at all, and the preparation of pheromone preparations with a limited sustained release period as described above requires trial and error even if conventional methods are simply used. It is. Not only that, but the range of target plasticizers, softeners, etc. is wide, and if there is no consideration for their chemical and physical properties, it must be said that it is no longer possible to select them. There is no situation.

For example, if physical constants such as the diffusion coefficient of a drug component in a polymer material as a base material when a volatile organic compound is used as a drug component are measured, the formulation can be effectively used by using these physical constants. The shape of the material or the design of the material to be used can be made easy.

That is, an object of the present invention is to provide an agricultural chemical formulation formed by impregnating a substance from a biodegradable polymer material with a volatile organic compound having an attracting, repelling, and killing effect on living organisms. The invention is characterized in that it is composed of only a biodegradable material that does not affect water release, provides a guideline for controlling the release rate, and provides a controlled pesticide formulation.

[0020]

The sustained-release preparation of biodegradable raw material of the present invention comprises a volatile organic compound which is volatile at room temperature in the atmosphere and acts on living organisms, and a biodegradable polymer material. A pesticide formulation containing a base material mainly composed of: a volatile organic compound having a diffusion coefficient D [cm ² / sec] and a surface transfer rate coefficient F [1 / cm] in the base material, which is determined at room temperature. Under the
The radius R of the preparation is adjusted so that the residual concentration relative to the initial concentration of the volatile organic compound after 30 days is 10% by weight or less.
With formula (I):

[0021]

R = {D / 2.5 × 10 ⁻⁷ / 10 ^{(0.0002 / (F−0.0023))} } (I)

When the desired release period exceeds 30 days, the radius is calculated by the following formula (I '):

[0023]

R _T = {D / 2.5 × 10 ⁻⁷ / 10 ^{(0.0002 / (F−0.0023))} } * (T / 30) (I ′)

The surface moving velocity coefficient F [1 / cm] in the above formulas (I) and (I ') is represented by the following formula (II):

[0025]

(Equation 6) C: Volatile organic compound concentration C _ATM : Volatile organic compound concentration in the outside r: Coefficient given by the length in the radial direction from the center as a starting point.

According to the present invention, when a volatile organic compound is used as a drug active ingredient and the release of the volatile organic compound from the preparation is sustained for a predetermined period when the preparation is made using a biodegradable base material, Suitable guidelines for determining the radius of the drug are provided, and the need to determine the relationship between the type of drug-forming material and the radius of the drug in consideration of the desired duration of release is greatly reduced. Thus, it is possible to provide an efficient sustained-release preparation of a volatile active drug component.

[0027]

BEST MODE FOR CARRYING OUT THE INVENTION In designing a sustained-release preparation, a material having characteristics such that the selected volatile organic compound can be effectively released is selected, and the release period is controlled by using the material. The shape of the processed pesticide formulation is also a very important factor. The present invention disclosed the fact that, with regard to the processed shape, the control of the release rate of the cord-like and thread-like preparations can be provided by defining the radius R in consideration of the physical properties of the material itself. Things.

The radius (R) in the present invention is the radius in the case of a spherical preparation, and refers to the radius of the cross section in the case of a preparation such as a string having a circular cross section.

Further, the radius R given by the invention
The criterion for the determination is that the residual concentration of the volatile organic compound after the release period of the pesticide formulation after 30 days is basically determined,
It is determined to be 10% by weight or less of the initial concentration. This is because when the target organism is an insect, the period during which its activity is active is often limited throughout the season, and it is therefore desirable that pesticides act during the active period. In the case of a release preparation, it is desirable that the pesticidal component be released during the period of activity. In the present invention, the content of 10% by weight or less is set as a standard for effectively using the pesticide contained in the preparation.

The reference of 30 days is such that the release period is adjusted to the period during which the activity of the organism such as pests on the crop is most active. Therefore, it can be said that this is a standard release control period. On the other hand, when the activity period of the creatures such as pests is longer than 30 days, it is a means to re-install a new one after the elapse of 30 days, and by using a thing with a larger diameter, roughly However, it is possible to extend the controlled release period. In general, on the basis of 30 days, in the same concentration state, the diameter of the pesticide formulation with respect to the extension period T is Δ (T / 30)
A tentative measure is to deal with it by doubling it.

The volatile organic compounds include apples, chestnuts,
Tastes of fruit trees such as persimmons, grapes, peaches, tangerines, etc., trees such as tea, cherry blossoms, camellia, roses, soybeans, sweet potatoes, peanuts, taros, or grains such as rice, wheat, corn, sugar cane, wasabi, etc. Crop-related, strawberry, chow,
For vegetables such as spinach, tomatoes and cucumbers, it is necessary to select and use those that have an effect or action on organisms that harm the leaves and roots of the vegetables or fruits and fruits. it can.

As the effect and action, those which exert a killing effect, a repellent effect, or an attraction effect on living organisms can be selected.

DDPV is known to have a killing effect.
Agent, PHC agent, DEP agent, MPP agent, MEP agent, PHC
And organic compounds having volatility at normal temperature, such as dianodine, isoxathion, prothiophos, phenothrin, and permethrin.

As the 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
For example, those disclosed in JP-A-1-132501 such as -ON can be used. In addition, dimethyldichlorovinyl phosphate, chloropicrin and the like are also effective.

Further, a typical pheromone having an attractive effect is a sex pheromone, which has recently been described.
Many pheromone components have been identified and manufactured. The target is a lot of insects, such as moths, butterflies, chafers, beetles and the like. Specific examples thereof include, for example, isopentylamine-β-methylbutane.

Further, these volatile organic compounds as active pharmaceutical ingredients can be used in combination of two or more of them within a range that does not impair the intended effect.

It is said that the effect of these volatile organic compounds is exerted if there is one molecule per 1 cm ³ of the application area, and the effect is extremely small. Therefore, the vapor pressure may be slight. If the molecular weight is 400 or less and 100 or more, it is possible to have sufficient volatility as an active drug component of the sustained-release preparation, and there is no practical problem. More preferably, 3
It is 50 or less and 130 or more, and most preferably 320 or less.

The proportion of the volatile organic compound in the sustained-release preparation is preferably 0.1% by weight or more and 10% by weight or less based on the whole preparation, and the lower limit is 0.3%.
% By weight, and more preferably 4% by weight as the upper limit.

As the biodegradable polymer material which is the main constituent material of the substrate, one or more selected from the group consisting of polylactic acid, aliphatic polyester and polyethylene glycol can be used. . Polylactic acid includes poly-L-lactic acid, poly-D-lactic acid, and polyglycolic acid, and aliphatic esters include poly (3-hydroxybutyrate), poly-β-hydroxyalkanoate, and poly-lactic acid.
ω-hydroxyalkanoates, poly-ε-caprolactone, polybutylene succinate, polyethylene succinate and polygratin. Polyethylene glycol having a biodegradable molecular weight of up to 6000 is used.

Further, a mixture of a plurality of these polylactic acids, aliphatic polyesters and polyethylene glycols may be used. Further, the volume ratio of these biodegradable polymer materials contained in the sustained-release preparation is preferably 50% or more. When the volume is less than 50%, the ratio of oligomers or low molecular weight polymers used as additives and the total of volatile organic compounds exceed 50%, and a rigid shape is maintained. Becomes difficult.

The sustained-release preparation of the present invention may optionally contain
Additives can be added. For example, the additive mixed with the polylactic acid can make the glass transition temperature of the polylactic acid 50 ° C. or lower, and is not particularly limited as long as it has biodegradability. Examples of the additive include phosphoric acid esters, phthalic acid esters, aliphatic carboxylic acid esters, aliphatic alcohol esters, hydroxy polybasic acid esters, epoxy animal and vegetable oils, polyalkylene glycols, and the like. And these one
More than one species can be used.

Examples of the phosphoric acid esters of the additives shown in the present invention include tributyl phosphate, 2-ethylhexyl phosphate, triphenyl phosphate, tricresyl phosphate and the like.

The phthalic acid esters of the additives shown in the present invention include dimethyl phthalate, diethyl phthalate, dibutyl phthalate, diheptyl phthalate, dioctyl phthalate, 2-ethylhexyl phthalate, diisonoyl phthalate, octyl phthalate Decyl, diisodecyl phthalate, butylbenzyl phthalate and the like.

The aliphatic carboxylic acid esters of the additives shown in the present invention include butyl oleate, dimethyl adipate, diisobutyl adipate, dibutyl adipate,
Examples thereof include diisobutyl adipate, diisodecyl adipate, dibutyl diglycol adipate, di-n-hexyl adipate, di-2-ethylhexyl adipate, dibutyl sebacate, and di-2-ethylhexyl sebacate.

The aliphatic alcohol esters of the additives shown in the present invention include diethylene glycol dibenzoate, diethylene glycol monomethyl ether, diethylene glycol dimethyl ether, diethylene glycol monoethyl ether, diethylene glycol diethyl ether, diethylene glycol monobutyl ether,
Diethylene glycol dibutyl ether, diethylene glycol monohexyl ether, polydiethylene glycol monooleyl ether, triethylene glycol diacetate, triethylene glycol monoethyl ether, triethylene glycol monobutyl ether, triethylene glycol di-2-ethyl butyrate, triacetin, glycerin triacetate Glycerin tripropionate, glycerin monooleate and the like.

Examples of the hydroxy polybasic acid esters of the additives shown in the present invention include methyl acetyl ricinoleate, butyl acetyl ricinoleate, butyl phthalyl butyl glycolate, and tributyl acetylene citrate.

Epoxy animal and vegetable oils as additives in the present invention include epoxidized soybean oil and epoxidized linseed oil.

[0048] Examples of the polyalkylene glycol as an additive shown in the present invention include polyethylene glycol, polypropylene glycol, polybutylene glycol and the like.

The amount of these additives can be selected according to the volume of the volatile organic compound as the active drug component and the base material, but is preferably selected from the range of 15 to 50% by weight. Yes, the lower limit is 18% by weight
Is more preferable, and 20% by weight is even more preferable.

When these additives are mixed into the biodegradable polymer material serving as the base material, the resulting diffusion coefficient and surface transfer rate coefficient have different values. It is necessary to pay attention to the selection of additives. However, if it is an additive that improves the release characteristics, in accordance with the desired pesticide duration T,
The radius R determined based on the formula (I) can be determined.

That is, the present invention provides a very important guide for controlling the release rate of the volatile organic compound contained in the sustained-release preparation composed of these materials. Therefore, the sustained-release preparation prepared according to the contents disclosed in the present invention can release a volatile organic compound in a desired period, greatly contributing to the efficiency in agricultural work, and economical use of pesticides. Results in more efficient use.

However, an effective release characteristic cannot be obtained simply by mixing a volatile organic compound with a polymer material such as polylactic acid. For example, it has been confirmed that a sustained-release preparation formed by kneading a volatile organic compound using only polylactic acid without using an additive does not readily emit a volatile organic compound under ordinary temperature conditions. For example, an amine-based volatile attractant was used as a volatile organic compound, and the release characteristics of a case where only polylactic acid was used as a base material were evaluated, but the release amount was found to be very small. Was.

This is because, although the volatile organic compound is contained in the polylactic acid, the polylactic acid itself has a rigid property, so that the polylactic acid itself is contained in the polymer chain of the volatile organic compound polylactic acid. It is immobilized and its movement is severely restricted.

Then, the present inventors used the sustained-release preparation shaped like a string to obtain the following formula (III):

[0055]

(Equation 7) C: Concentration of volatile organic compound t: Elapsed time Diffusion equation was derived based on the cylindrical coordinate system. This diffusion equation includes a diffusion coefficient D [cm ² / sec] which is an important element in the present invention.

As an initial condition, it is assumed that the volatile organic compound is uniformly dispersed in the sustained-release preparation at an initial concentration given at the time of production. This is in line with the actual situation, and the sustained-release preparation impregnated with volatile organic compounds is covered with an aluminum foil lami-sheet so that the volatile organic compounds do not escape to the outside before use. This is because the assumption of uniform dispersion in a sustained-release preparation is considered to be sufficiently consistent.

The boundary condition is given by the above equation (II). The surface moving speed describes a moving speed related to evaporation or detachment from a pesticide surface having a columnar shape suitable for expressing a string-like or thread-like shape.

FIG. 1 shows the model obtained in this way under the equations, initial conditions, and boundary conditions. FIG. 1 shows a cylindrical model, in which coefficients and parameters in each model are illustrated.

Further, when the given equations are put together, an equation group as shown below is given. That is,

[0060]

(Equation 8) Becomes

FIG. 2 shows a result of a simulation performed by a computer using these equations. At the same time, in FIG. 2, the actual measurement results having typical emission characteristics are indicated by □, and the diffusion coefficient D and the surface moving velocity coefficient F
In addition, it is possible to display a comparison with the result of the simulation for giving the radius R.

Here, the actual measurement results having typical release characteristics are obtained by using a pheromone preparation obtained by impregnating an ethylene vinyl acetate copolymer with a pheromone as a volatile attractant having an attracting effect on insects. And based on the results of measuring the release characteristics.

Therefore, in order to arrange this data, the radius R is fixed, and the diffusion coefficient D
FIG. 3 shows the result of displaying the relationship between the velocity and the surface movement velocity coefficient F. The result shown in FIG. 3 shows a combination of the diffusion coefficient D and the surface moving velocity coefficient F, which was able to simulate the measured data indicated by □ in FIG. . Furthermore, this diffusion coefficient D
Assuming that the boundary line represented by the combination of the line and the surface moving speed coefficient F is [line 1], the region at the upper right of the region given by [line 1], that is, the region where both the diffusion coefficient D and the surface moving speed coefficient F are large Is a region where the volatile organic compound emits faster than the measured value in the figure, and conversely, the range on the left and below the region given by [Line 1] is a region where the emission is slower than the measured value. .

Further, as the next step, a combination of the diffusion coefficient D and the surface moving velocity coefficient F that establish the actual measured value in FIG. 2 is displayed as in FIG. 3 when the radius R is changed. Is shown in FIG. At this time, the radius R used for the simulation was 1 cm, 0.1 cm,
They are 0.01 cm and 0.001 cm. As shown in FIG. 4, it has been found that the region where the combination of the diffusion coefficient D and the surface moving velocity coefficient F obtained by the difference in the radius R is established has a certain relationship.

The essence of the present invention is obtained by obtaining an equation representing this relationship. Next, the development procedure will be described.

First, the diffusion coefficient D is displayed on the Y-axis.
Represented by The X axis is represented by the surface movement speed coefficient F.

At this time, [Line 1] can be approximated by a hyperbolic equation expressed by the following equation (IV).
That is,

[0068]

[Mathematical formula-see original document] logD = A / (FB) + C (IV) A, B, C: can be represented by a basic formula using given constants.

Referring to FIG. 4, a procedure for obtaining constants A, B, and C such that the following equation (IV) holds will be described.

First, the physical meaning of the hyperbola shown in FIG. 4 will be considered. Even when the diffusion coefficient D increases, the emission rate of the volatile organic compound is no longer limited by the surface movement rate coefficient. Conversely, even if the surface moving speed is increased, it is limited by the diffusion speed defined by the diffusion coefficient. The line limited by the diffusion coefficient D is represented by an asymptote parallel to the X axis. On the other hand, the line limited by the surface moving velocity coefficient is represented by an asymptote parallel to the Y axis. As described above, two X axes, Y
Along an asymptote parallel to each axis
Can be defined.

Therefore, among the constants A, B, and C to be obtained,
Regarding the constant B, the value of the surface moving velocity coefficient F of the asymptote on the X axis, that is, 0.0023 [1 / cm] in FIG. Further, the constant A is the value of the logarithmic diffusion coefficient logD of the asymptote on the Y-axis, that is, in FIG. 4, when the radius R is 1 cm, C = log (5 × 10 ⁻⁷ ). Further, the position of the drawn hyperbola moves in parallel according to the value of the radius R. When the value of the constant C is determined in consideration of this element, C = log (2.5 × 10 ⁻⁷ * R ² ).

The constant A is the slope of the hyperbola, and the value of A determined by the least square method is 2 × 10 ⁻⁴ .

When the equation obtained as described above is described again,

[0074]

[Equation 10] log D = 2 × 10 ⁻⁴ /(F−0.0023)+log
(2.5 × 10 ⁻⁷ * R ² ).

Further, when deformed,

[0076]

[ ^{Mathematical formula-see original document} ] R = {D / 2.5 * 10 < ^-7 > / 10 ^{(0.0002 / (F-0.0023))} }.

As described above, the shape of the desired sustained-release preparation can be determined by measuring the volatile organic compound release characteristics of the biodegradable polymer material impregnated with the volatile organic compound. Became.

In addition, the biodegradable polymer material serving as the base material may contain an inorganic compound containing silicon dioxide as a main component. These inorganic compounds containing silicon dioxide as a main component are for inhibiting association of a polymer.

In the production of polylactic acid in the present invention, lactic acid is used as a raw material, and the lactic acid is L-lactic acid, D-lactic acid, D, L-lactic acid or a mixture thereof, or lactide which is a cyclic dimer of lactic acid. Can be used.

The polylactic acid used in the present invention is prepared by directly dehydrating and condensing lactic acid having an L-lactic acid content of 75% by weight or more, or by ring-opening using lactide which is a cyclic dimer of the lactic acid. It is obtained by a method of polymerizing. In the case of direct dehydration / condensation, lactic acid is preferably subjected to azeotropic dehydration / condensation in the presence of an organic solvent, particularly preferably a phenyl ether-based solvent, and particularly preferably, water is removed from the solvent distilled by azeotropic distillation to obtain substantially anhydrous water. Polymerization by a method of returning the solvent in the state described in the above to the reaction system gives a high molecular weight polylactic acid having strength suitable for the present invention.

The weight average molecular weight (Mw) and molecular weight distribution of the polylactic acid are not particularly limited as long as they can be formed substantially. The molecular weight of the polylactic acid used in the present invention is a weight-average molecular weight of 4 which shows substantially sufficient mechanical properties.
The weight average molecular weight (Mw) is preferably from 40,000 to 200,000, and the upper limit is 150,000, and the lower limit is more preferably 60,000.

Generally, the weight average molecular weight (Mw) is 4
If the molecular weight is smaller than 10,000, the mechanical properties are not sufficient, or if the molecular weight exceeds 200,000, the viscosity in the molten state becomes high, handling becomes difficult, the production time becomes longer, and the production cost increases. It may be expensive or uneconomical.

As a method for obtaining a string-shaped sustained-release preparation having a desired radius, a volatile organic compound is mixed with a biodegradable polymer together with a silicon dioxide powder and an additive as a blocking inhibitor at 160 ° C. Under the above temperature atmosphere, mixing by a ball mill is performed for a predetermined time. Next, the uniform raw material powder of the controlled release body is extruded through a single die with an extruder, and is taken up by a spinning winder.

Further, by changing the melting temperature of the biodegradable polymer, the diameter of the die hole, and the winding speed,
String-shaped sustained-release preparations having different radii can be obtained. As a result, by reducing the diameter of the die hole and increasing the winding speed, it is also possible to obtain a thread-like preparation having a smaller radius.

[0085]

Embodiments of the present invention will be described below in detail. [Example 1] As a volatile organic compound, an amine-based volatile attractant which is a kind of agricultural chemical (hereinafter abbreviated as attractant)
Was used. Furthermore, as a biodegradable polymer compound as a base material, polylactic acid (trade name: Leicia (H) manufactured by Mitsui Chemicals, Inc.
-100 J, hereinafter abbreviated as PLA). This is included in the biodegradable polymer material group used as the substrate. Furthermore, while containing 4% by weight of silicon dioxide as an anti-blocking agent, as a plasticizer,
Triethylene glycol diacetate (hereinafter TEDA)
). In addition, as a volatile organic compound,
PLA / silicon dioxide / TED in the system containing the same drug having an attracting effect on insects as in Example 1
A / attractant = 63/29/4/4 (% by weight) were mixed and mixed by a ball mill having 100 balls for 30 minutes.

Next, the homogenized raw material powder of the release control body was extruded with a Labo Plastomill extruder [biaxial (25 mm
φ), a single die (4.0 mmφ)], and extruded with a take-up winder.

The finished sustained-release preparation has a radius of 1.3 mm.
Met. This preparation was placed in a blow dryer set at a set temperature of 30 ° C. and an average wind speed of 0.3 m / sec, and the residual amount of the drug having an attraction effect was measured over time to calculate the residual ratio. Show. After 30 days, it was recognized that the residual drug concentration was 10% by weight or less of the initial value.

In order to satisfy the emission characteristics obtained from the experimental results, the diffusion coefficient and the surface movement velocity coefficient are calculated by the equations (II), (III) and a group of equations expressed by the equations giving the initial conditions. Ask as needed. FIG. 6 shows a combination of the diffusion coefficient and the surface moving velocity coefficient obtained by this method.

For example, a combination of a diffusion coefficient and a surface transfer coefficient that satisfies the results of the emission curve shown in FIG.
It can be seen that when the diffusion coefficient is 9 × 10 ⁻⁹ cm and the surface transfer coefficient is 0.0029 cm ⁻¹ , the concentration of the remaining attractant becomes 10% by weight or less of the initial value after 30 days.

Further, the obtained diffusion coefficient was 9 × 10 ⁻⁹ cm,
When the radius R is calculated by substituting the surface movement coefficient 0.0029 cm ^{-1 into the} equation (I), the following is obtained.

[0091]

R = √ ｛9 × 10 ⁻⁹ /2.5×10 ⁻⁷ / 10
^{(0.0002 / (0.0029-0.069 / 30))} ｝ = ^0.129 [cm], which was confirmed to be equal to the given radius value of 1.3 mm.

Therefore, a sustained-release preparation having the same composition having another radius was prepared using the formula (I), and its release characteristics were measured. Since the compositions are the same, the assumed diffusion coefficient and surface transfer coefficient are as follows.

Diffusion coefficient = 9 × 10 ^-9 [cm] Surface transfer coefficient = 0.0029 [1 / cm] First, when a sustained-release preparation having a radius of 3 mm was prepared, the residual drug concentration was reduced to 10% by weight or less of the initial value. It turned out after 60 days had passed.

When a sustained-release preparation having a radius of 0.75 mm was prepared, it did not take 15 days for the residual drug concentration to become 10% by weight or less of the initial value.

From the above results, it can be confirmed that the sustained-release preparation prepared using the formula (I) exhibits desired properties.

Therefore, in this example, it was confirmed that the release characteristics of the volatile organic compound impregnated in the sustained-release preparation containing a biodegradable polymer as a base material can be very closely approximated.

[0097]

According to the sustained release preparation of the present invention, the compound added as an additive to the polymer contains a volatile organic compound having repellency and attractiveness as an agrochemical component, and at the same time, the release rate is increased. It has a function of controlling, and exhibits extremely excellent performance in improving the efficiency and simplification of the work of farmers.

Further, a simple release test result of the obtained sustained-release preparation using a biodegradable polymer as a base material, and the results obtained by the simulation, such as a diffusion coefficient and a surface transfer rate coefficient obtained from simulation results. From these figures, it is possible to easily design the shape to obtain the desired sustained release days.

The base material is made of a biodegradable material and a volatile organic compound harmless to the human body, so that there is no concern about environmental pollution.

As described above, the present invention is an extremely valuable invention from the industrial and global environmental viewpoints.

[Brief description of the drawings]

FIG. 1 is a model diagram of cylindrical coordinates used in calculations of the present invention.

FIG. 2 is a diagram showing measured results of release characteristics of a sustained-release preparation having typical release characteristics and simulation results thereof.

FIG. 3 is a diagram showing a result of displaying a relationship between a diffusion coefficient D and a surface moving speed coefficient F used in a simulation.

FIG. 4 shows that the radius R of the sustained-release preparation of the present invention is 1 cm, 0.1
FIG. 9 is a diagram illustrating a range in which a combination of a diffusion coefficient D and a surface movement velocity coefficient F obtained in a simulation is established in the case of cm, 0.01 cm, and 0.001 cm.

FIG. 5 is a view showing a measurement result of a residual amount of a volatile attractant in Example 1.

FIG. 6 is a diagram showing a range in which a diffusion coefficient and a surface moving velocity coefficient satisfying emission characteristic results in Example 1 are satisfied;

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Shohei Nozaki 1190 Kasama-cho, Sakae-ku, Yokohama-shi, Kanagawa Mitsui Chemicals, Inc.

Claims (6)

[Claims] 1. A pesticide formulation comprising a volatile organic compound which is volatile in a room temperature atmosphere and acts on living organisms, and a base material mainly composed of a biodegradable polymer material. Organic compound diffuses in substrate material D [cm ² / sec]
From the surface transfer rate coefficient F [1 / cm], the radius R of the preparation is adjusted so that the residual concentration relative to the initial concentration of the volatile organic compound after 30 days is 10% by weight or less under room temperature conditions. ^Is given by the following formula (I): R = {D / 2.5 × 10 ⁻⁷ / 10 ^{(0.0002 / (F−0.0023))} } (I) Sustained-release preparation. 2. A pesticide formulation comprising a volatile organic compound which is volatile in a room temperature atmosphere and acts on living organisms, and a base material mainly composed of a biodegradable polymer material. Organic compound diffuses in substrate material D [cm ² / sec]
And the surface transfer rate coefficient F [1 / cm], the radius R of the preparation is adjusted so that the residual concentration relative to the initial concentration of the volatile organic compound after the elapse of T days is 10% by weight or less under room temperature conditions. ^{Is given} by the following equation (I ′): R _T = {D / 2.5 × 10 ⁻⁷ / 10 ^{(0.0002 / (F−0.0023))} } * (T / 30) (I ′) A biodegradable sustained-release preparation characterized by giving. 3. The surface moving speed coefficient F [1 / cm] is expressed by the following formula (II): C: Concentration of volatile organic compound C _ATM : Concentration of volatile organic compound in the outside world r: Coefficient given by the length in the radial direction from the center as a starting point The biodegradable sustained release according to claim 1 or 2. Formulation. 4. The radius R or R _T is not more than 1 cm and 0.0
The biodegradable sustained-release preparation according to any one of claims 1 to 3, which is not less than 01 cm. 5. The method according to claim 1, wherein the base material is selected from the group consisting of polylactic acid, aliphatic polyester and polyethylene glycol.
More than one kind of biodegradable polymer material, furthermore, aliphatic dibasic acid ester, phthalic acid ester, hydroxy polycarboxylic acid ester, caprolactone, polycondensation product of dicarboxylic acid and diol, polycondensation product of hydroxy acid The biodegradable product according to any one of claims 1 to 5, further comprising at least one additive selected from the group consisting of ethylene glycol, a polymer thereof, and vinyl alcohol and a polymer thereof. Sustained-release preparations. 6. The biodegradable sustained-release preparation according to claim 1, wherein the volatile organic compound has any of a biological killing effect, a biological repellent effect, and a biological attracting effect.