KR20070025298A - A matrix-typed, sustained-releasing agent comprising biological effective ingredients being capable of recognizing a content of moisture and a process for producing the same - Google Patents

Abstract

A method for preparing a controlled-release pesticide or a fertilizer is provided to conveniently and cleanly produce the pesticide or fertilizer without dissolving raw materials of the pesticide or fertilizer in an organic solvent in advance and obtain the pesticide or fertilizer whose active materials' effect expressing period is controlled with less phytotoxicity. The method comprises the steps of: (a) after adding 0.05-15 parts by weight of a polysaccharide and 0.3-20 parts by weight of an inorganic alkali regarding 1000 parts by weight of a porous carrier into a base solvent such as water, alcohol, acetone, acetonitrile, dioxane, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran and a mixture thereof and adding a first release controlling agent thereto so as to adjust the pH of the solution into 9-12, adding 0.0005-150 parts by weight of a biologically active material, which is selected from the group consisting of insecticide, herbicide, plant growth controlling agent, nematocide, fungicide, sterilizer, rodenticide, fumigation agent, animal and insect repellent, biological insect exterminator, pheromone, sex attractant, flavoring agent, aromatic, dietary supplement, medicine and fertilizer, and a mixture thereof, thereto with agitation and then adding a second release controlling agent thereto so as to adjust the pH into less than 9 with agitation to prepare an active material solution; and (b) after uniformly mixing the active material solution with 1000 parts by weight of the porous carrier, drying it at a temperature of 25-150 deg.C to form a controlled-release film.

Description

Sustained-releasing Agent Comprising Biological Effective Ingredients Being Capable of Recognizing a Content of Moisture and A Process for Producing the Same

Figure 1 is a photograph showing the gelling properties of the polysaccharide added with a release control agent according to the method of the present invention.

Figure 2 is a photograph showing the biodegradation delay effect of the polysaccharides by the organic acid.

Figure 3 is a photograph showing the biodegradation delay effect of the polysaccharides by organic acids maintained in the soil.

4 is a photograph of a visual model of a sustained release formulation according to the present invention.

Figure 5 is a photograph showing the dissolution test results with time of the sustained release formulation and the control according to the present invention.

Figure 6 is a photograph showing the sustained release formulations recovered after the dissolution test with time for the sustained release formulation and the control according to the present invention.

Figure 7 is a photograph showing the formation of a sustained-release preparation containing a biologically active substance, in the photo Meto-A, Meto-B, Meto-C is a control and Meto-D is a sustained release prepared by the method of the present invention Formulation.

The present invention relates to a sustained-release moisture-recognition matrix formulation comprising a biologically active substance and a method for preparing the same, and more particularly, to form a matrix by coating a biologically active substance such as pesticides or fertilizers adsorbed on a porous carrier with polysaccharides. The present invention relates to a sustained release preparation of a biologically active substance in which the release of the biologically active substance is controlled according to the amount of post-moisture absorption and the time of exposure to moisture, and a method for preparing the same.

Vegetables such as lettuce, cucumbers, tomatoes, and pesticides used to control pests such as fruit trees, flowers, and cereals, or fertilizers used to supply nutrients to these crops, are generally granulated in liquid form or excipients mixed with water. Has a form. Conventional pesticides or fertilizers of the general form are spilled, refrained, or evaporated out of the area being sprayed to quickly reduce the active ingredient concentration. For this reason, since the duration of drug efficacy is usually short, there is a tendency to spray several times in excess of the amount or concentration in use. The excessive use of pesticides or fertilizers causes various health problems for farmers and crop consumers, and causes serious environmental pollution due to salt accumulation and eutrophication due to continuous spraying and irrigation on soil.

Accordingly, by providing sustained release to biologically active substances, such as pesticides and fertilizers, in solid or liquid phase, by spraying the pesticide or fertilizer at an appropriate concentration at a time, controlling the timing of activity of the biologically active substances so that the effect is maintained for a long time. Research for this is being actively conducted.

Methods for producing sustained-release pesticides include: 1) placing the pesticide active material in microcapsules; 2) enclosing the pesticide actives in cyclodextrins; 3) Japanese patent Agrochemical preparations such as granules and powders are prepared by mixing the active substances alone or with an extender and the like to produce the particles, and coating the produced particles with a resin.

Japanese Patent No. 194-116103 discloses a method of introducing sustained release by introducing a pesticide dissolved in a solvent into a biodegradable resin injected into a plate, and Japanese Patent No. 1993-85902 discloses a biodegradable polymer in a pesticide raw material. A method of producing a sustained-release pesticide is disclosed by mixing, dissolving in chloroform, adsorbing on granular zeolite, heating and evaporating chloroform.

Korean Patent No. 10-408157 discloses that the active material solution obtained by first dissolving a biologically active material in a predetermined volume of solvent is homogeneously mixed with a coating solution containing a polysaccharide, an inorganic alkali and a release regulator, and then mixed with the solution and a porous carrier. A method of preparing a sustained release formulation of a biologically active substance by post-drying is described. In this method, the sustained-release preparation was prepared by dissolving each biologically active ingredient in methanol according to a conventional method. In the method of the registered patent, it is inevitable to use an organic solvent to dissolve the biologically active agent, and if the original agent is dissolved in the organic solvent, a sustained-release preparation capable of loading a large amount of physiologically active substance required by the market is prepared. It is difficult to manufacture and there are limitations to the emission pattern control.

A technique for coating other pesticide active materials with a solid, water-insoluble low-melting beeswax material and supporting them on granular fertilizers (Korean Patent Publication No. 1989-4995), wherein the carrier containing the pesticide is a polyhydroxylated compound or a polyisocyanate. Interfacial polymerization reaction to form a polyurea barrier membrane (Korean Patent No. 1992-7002910), a method of mixing and injection molding the pesticide active material with a biodegradable resin and release control agent (Korean Patent No. 2000-42895), By impregnating active materials such as fertilizers or pesticides using pulp including waste paper as a matrix, and then forming a primary resin coating layer and a secondary sulfur coating layer, the sustained release of the active substance impregnated with the impregnating agent Sustained release (Korea Patent Publication No. 2000-2248) and the like are known to increase the sustained release of fertilizers and pesticides having increased.

However, the above methods are 1) complicated manufacturing process or limited application, 2) high production cost, which is a burden to use for improving pesticides or fertilizers, 3) causing harmful manufacturing environment due to the use of solvents in the manufacturing process In particular, 4) there is a problem that the sustained release effect is difficult to be exhibited due to insufficient control of emission control such as rapid biodegradation of the coating layer in actual soil application.

That is, depending on the type of pesticide compound, there are some pesticide compounds that cannot be prepared in sustained-release preparations due to the encapsulation of microcapsules or the inclusion of a cyclodextrin and a clathrate compound. In addition, the sustained-release effect of the pesticide preparation obtained by applying the conventional method for producing a sustained-release preparation is insufficient, and in many cases, the sustainability and extension of biological activity, which is one of the objectives of sustained-release pesticides, and reduction of weakening cannot be sufficiently achieved. Due to the complex manufacturing techniques of sustained-release pesticides or the raw materials used are expensive, there are still problems to be solved in technical or economic terms.

Pesticide raw materials are mostly dissolved in organic solvents because they have very low solubility in water. However, organic solvents are toxic and the use of organic solvents in conventional pesticide formulations is extremely limited due to the recent environmental problems. There is an urgent need to develop a method for preparing a sustained-release pesticide preparation by directly administering the pesticide in its original form without using it.

Therefore, there is a need to develop new techniques for sustained release formulations containing a pesticide or fertilizer composition as a biologically active substance and / or a method for preparing the same.

On the other hand, a method for coating microorganisms with polysaccharides is known, although not for sustained release of the pesticide component. For example, the invention described in Korean Patent Application No. 10-2000-17801 relates to a method of coating a microorganism to have heat resistance and acid resistance by using a microorganism-derived polysaccharide. This microbial coating is to protect the microorganisms from gastric acid and various intestinal digestive enzymes when ingesting microorganisms (such as lactic acid bacteria) useful for the human body so that the microorganisms can be seated in the small and large intestine. Therefore, the microbial coating must reach the necessary site (small intestine and large intestine) while maintaining resistance to acid, heat and digestive enzymes, and the coating must be dismantled immediately so that the microorganism can adhere to and grow in the small intestine and large intestine. Microbial coatings belong to a completely different field from the manufacture of sustained-release pesticides which allow the active material to be released slowly.

The present invention to solve the problems of the prior art as described above, an object of the present invention is to provide a sustained-release preparation of a biologically active substance is simple to manufacture and a method for producing the same.

It is an object of the present invention to provide a method for preparing a sustained release preparation of a biologically active substance at low cost and a simple method, and a sustained release formulation of a biologically active substance having controlled release control prepared by the method.

It is an object of the present invention to provide a clean manufacturing method capable of preparing a sustained release preparation of a biologically active substance without using a separate solvent for the biologically active substance in the manufacturing process.

It is another object of the present invention to provide a biologically active substance formulation and a method for producing the same, which are environmentally friendly and have excellent sustained release.

In one aspect, the invention

1) 0.05 to 15 parts by weight of a polysaccharide and 0.3 to 20 parts by weight of an inorganic alkali are added to the base solvent with respect to 1000 parts by weight of the porous carrier, and a first release controlling agent is added to adjust the pH of the solution to 12 to 9 Adding 0.0005 to 150 parts by weight of a biologically active substance of agitation, adding a second release controlling agent so that the pH of the total solution is 9 or less, and preparing the active substance solution; And

2) sustained release of the biologically active material comprising the step of homogeneously mixing the active material solution obtained in step 1) with 1000 parts by weight of the porous carrier and drying at a temperature of 25 to 150 ℃ Provided are methods for preparing the sexual formulation.

On the other hand, in the sustained release preparation of the biologically active substance according to the present invention, the biologically active substance may be present in the porous carrier or the sustained release membrane.

In the present invention, the 'base solvent' refers to a base solution for generating a matrix by polysaccharide, and is distinguished from a solvent conventionally used for dissolving a biologically active substance. In the present invention, the biologically active substance may be used in the form of an original regardless of hydrophobicity or hydrophilicity. The base solvent usable in the present invention may be selected from, for example, water, alcohol, acetone, acetonitrile, dioxane, dimethylformamide, dimethylsulfoxide, tetrahydrofuran or mixtures thereof, preferably water use.

In the present invention, as the inorganic alkali, KOH, NaOH, NH ₄ OH aqueous solution and the like may be used, and preferably 0.3 to 20 parts by weight based on 1000 parts by weight of the porous carrier. Inorganic alkali is added to stabilize the pH change by the release modifiers added to control the gelation reaction of the polysaccharides and to control the release of the matrix lattice formed by the polysaccharides.

In the present invention, the 'release control agent' is an organic acid, an inorganic acid or a mixture thereof added to control the matrix lattice size of the polysaccharide before and after the addition of the biologically active substance, and when the first and second release regulators are added. The same compound may be used for the classification according to, or different compounds may be used. Preferably, the release controlling agent is selected from phosphorous acid, phosphoric acid, acetic acid, hydrochloric acid, boric acid or mixtures thereof.

In the present invention, the first release controlling agent is added primarily for pH control of the base solvent solution in which the polysaccharide and the inorganic alkali are dissolved before adding the biologically active substance. That is, the first release regulator is added so that the pH of the base solvent containing the polysaccharide and the inorganic alkali is 12 to 9, but if the biologically active substance is acidic, the first release regulator may not be added.

The base solvent solution containing the polysaccharide, the inorganic alkali, the first release controlling agent, and the biologically active substance prepared as described above begins to proceed to gelation at around pH 12. In addition to this, a second release modifier is added, which, when added, reduces the lattice size of the matrix formed by the polysaccharides, so that the biologically active material is trapped in the lattice, so that a larger amount of the biologically active substance is contained in the matrix. Can be. The second release controlling agent is added until the gelation of the total solution is complete, preferably until the pH of the total solution reaches 9 or less.

According to the present invention, the release of the active material is suppressed by the adsorption of the porous carrier itself and the biologically active material, and the release of the active material by the sustained release membrane made of a polysaccharide trapping the porous carrier adsorbing the biologically active material in the matrix lattice structure. Emission is suppressed.

In the sustained-release preparation according to the present invention, the biologically active substance is adsorbed on the porous carrier or evenly contained in the sustained release membrane, and thus the release of the biologically active substance is controlled according to the amount of the absorbed moisture in the dry state and is formed by polysaccharide. The matrix has been inhibited for some time to exhibit the effect of slowly releasing the biologically active substance out of the sustained release formulation.

The sustained-release preparation of the biologically active substance is a matrix lattice of the sustained-release membrane is opened by the water absorption to release the release regulator present in the membrane first and secondary release of the biologically active substance through the micro-hole space formed by the release When the water evaporates, the lattice is closed again and the release of the active material can be controlled in two to three stages where the release of the active material is stopped. The release of the biologically active substance is controlled by the staged release of the active substance.

In addition, the release control agent contained in the sustained-release membrane inhibits the biodegradation (by microorganisms) of the polysaccharide constituting the sustained-release membrane component, thereby maintaining the matrix structure for a long time to help sustain sustained release.

Sustained release preparations of biologically active substances prepared according to the present invention can collect a large amount of biologically active substances and can be easily controlled for release to increase the convenience of work during spraying and also sustained release in soil.

In the present invention, the porous carrier is a natural mineral zeolite, pearlite, vermiculite, diatomaceous earth, ceramics, activated carbon, white carbon, bentonite and sand, which are commonly used as main ingredients of excipients and extenders in the preparation of soil modifiers and pesticides. One or two or more mixtures selected from the group consisting of these may be used, and in addition, any carrier having soil affinity may be used. The carrier may be used as it is, or may be one obtained by treating the raw material at a high temperature of 600 ° C. or higher, that is, a calcined carrier, in order to remove impurities in the interior and to make the condition inside the carrier at the best condition.

The porous carrier adsorbs a biologically active material to absolutely reduce its diffusion property, and serves to widen the contact surface so that the sustained release film coated on the surface does not detach.

On the other hand, the sustained-release formulation according to the present invention can be applied to the soil by using a hand or spraying device, for this purpose, the preferred particle size range is 0.5 to 5 mm, usually diameter 2 mm or more workability when applied Not only is this good, it doesn't disperse into the air and it falls to the ground, increasing its effectiveness. Of course, the particle size may be adjusted to be smaller or larger than the above-mentioned range depending on the application method or the use, such as manual spraying, mechanical spraying or air spraying.

In the present invention, as the polysaccharide is degradable in nature, festan, levane, xantham gum, pullulan, polysaccharide-7, cellulose, juglan, gellan, curdlan or a suitable mixture thereof may be used. Here is the use of curdlan.

In the present invention, 'biologically active substance in its original form' means both the prepared or obtained intact biologically active substance solid or liquid which is not dissolved in a solvent.

Biologically active substances to which the present invention can be applied include insecticides, herbicides, plant growth regulators, nematicides, fungicides, fungicides, rodenticides, fumigants, animal and pest control agents, biopesticides, pheromones, sex attractants, flavorants, fragrances, Dietary supplements, drugs and fertilizers. The biologically active substance may preferably be used in an amount of 0.005 to 150 parts by weight based on the porous carrier. In the present invention, since the biologically active substance can be used directly in the form of a raw material without dissolving in a solvent, a larger amount of the active substance can be contained in the matrix lattice.

In the sustained-release preparation according to the present invention, the content of the biologically active substance can be appropriately selected depending on the kind and specific activity of the active substance.

Examples of the pesticide ingredient include insecticidal active ingredients, bactericidal active ingredients, herbicidal active ingredients and plant growth active ingredients. However, the active ingredient is not limited to those exemplified.

Insecticidal active ingredients include Acephate, Isoxathion, Imidacloprid, Ethylthiodemeton, Ethofenprox, Cartap, Carbosulfan ), Copenpentezine, Cyclopyrifas-methyl, Fenbutatin-oxide, Cycloloprothrin, Dimetylrinphos, Dimethoate, Silas Silafluofen, Diazinon, Thiodicarb, Thiocyclam, Tebufenozide, Nitenpyram, Vamidothion, Bifenthrin (Bifenthrin), Pyridaphenthion, Pyridaben, Pyrimiphos-methyl, Fipronil, Phenisobromolate, Buprofezin , Furathiocarb, Propafos, Ben Sultap (B) ensultap, benfuracarb, formothion, marathon, monocrotophos, BPMC, CVMC, DEP, EPN, MEP, MIPC, MPP, MTMC, NAC, PAP, PHC, PMP , XMC, and the like.

Examples of bactericidal active ingredients include phosphite, acibenzolar-S-methyl, azoxystrobin, bitanol, isoprothiolane, isopurodione and isoprodionate. (Iminoctadine triacetate), Oxolinic acid, Oxone-copper, Kasugamycin, Carpropamid, Captan, Diclomezine, Thiabenda Thiabendazole, Thifluzamide, Tecloftalam, Tricyclazole, Varidamycin, Hydroxyisoxazole, Pyroquilon, Phenariquina Fenarimol, Ferrimzone, Fthalide, Blasticidin, Polyoxin, Metasulfocarb, Metalaxyl, Metalaxyl-M, Meme Tominostrobin, Mepronil, Ampicillin, CNA, IBP, DF -351, NNF-9425, NNF-9850, etc. are mentioned.

Herbicidal active ingredients and plant growth regulators include Azimsulfuron, Atrazine, Amethin, Inabenfide, Imazosulfuron, Uniconazole and Espro Esprocarb, Etobenzanid, Oxadiazon, Carfenstrole, Quizarofop-ethyl, Quinclorac, Cumylron, Chlomethoxynil, Cyclosulfamuron, Dithiopyr, Cinosulfuron, Cyhalofop-butyl, Simazine, Dimethamerin (Dimetametryn) ), Dimepiperate, Cinmethylin, Dymron, Thenylchor, Triaphentenol, Naproanilide, Paclobutrazol , Bifenox, Piperophos, Pyrazoxyfen, Pyrazulfuronethyl (Pyr) azosulfuron-ethyl, Pyrazolate, Pyributicarb, Pyriminobac-methyl, Butachlor, Butamifos, Pretiilachlor, Pretilachlor, Bro Bromobutide, Bensulfuron-methyl, Benzofenap, Bentazon, Benticarb, Pentoxazone, Benfuresate, Mefenase Mefenacet, molinate, Jasmonic acid (JA), salicylic acid (SA), BABA, BTH, ACN, CNP, 2,4-D, MCPB, MCPB ethyl and the like.

In the present invention, preferred biologically active substances are imazaquin, napropamide, metolachlor, and the like.

In the present invention, the above various biologically active substances may be applied alone, or a plurality of active substances may be applied to one sustained release formulation by appropriate combination and combination.

Hereinafter, the manufacturing method of a sustained-release preparation by this invention is demonstrated. According to the method of the present invention, the biologically active material raw material can be used as it is, without using the conventionally used organic solvent. The water used in the following preparation is only a base for supporting the respective components and the base is not limited to water, but water is preferably a component that evaporates and is removed during the manufacturing process. . In addition, the amount to be used may be arbitrarily determined to a degree suitable for workability of the manufacturing process.

(I) the active substance in powder form Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

Sustained release preparations of biologically active substances according to the invention are prepared by the following process:

First, 0.05 to 15 g of polysaccharide, 0.3 to 20 g of inorganic alkali such as KOH, are dissolved in a predetermined volume of a base solvent, for example, 200 ml of water, and an organic acid and inorganic acid such as phosphorous acid, phosphoric acid, acetic acid, hydrochloric acid, or boric acid are added thereto. The pH of the solution is adjusted to 12 to 9 by the addition of one or more first release regulators selected from the group consisting of 0.005 to 150 g of a powdered biologically active substance, followed by stirring, phosphorous acid, phosphoric acid, acetic acid, A suspended active substance solution is prepared by adding one or more second release controlling agents selected from the group consisting of organic acids such as hydrochloric acid and inorganic acids so that the pH of the total solution is 9 or less.

After homogeneously mixing the solution containing the active material and 1000 g of the porous carrier and dried at 25 to 150 ℃ to form a sustained-release film on the surface of the adsorption carrier to prepare a sustained-release preparation of the biologically active material.

At this time, the drying temperature may be arbitrarily determined by referring to the heat resistance of the active material, and the degree of drying of the sustained release formulation is 40% or less, preferably 35% or less, which is advantageous for storage and workability.

(II) the active substance in hydrophobic liquid form Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

Sustained release formulations of another biologically active substance according to the invention are prepared by the following procedure:

First, 0.05 to 15 g of polysaccharide, 0.3 to 20 g of inorganic alkali such as KOH, are dissolved in a predetermined volume of a base solvent, for example, 200 ml of water, and an organic acid and inorganic acid such as phosphorous acid, phosphoric acid, acetic acid, hydrochloric acid, or boric acid are added thereto. The pH of the solution is adjusted to 12 to 9 by the addition of one or more first release controlling agents selected from the group consisting of 0.005 to 150 ml of liquid biologically active substance, followed by stirring, phosphorous acid, phosphoric acid, acetic acid, A suspended active substance solution is prepared by adding one or more second release controlling agents selected from the group consisting of organic acids such as hydrochloric acid and inorganic acids so that the pH of the total solution is 9 or less.

After homogeneously mixing the solution containing the active material and 1000 g of the porous carrier and dried at 25 to 150 ℃ to form a sustained-release film on the surface of the adsorption carrier to prepare a sustained-release preparation of the biologically active material.

At this time, the drying temperature may be arbitrarily determined with reference to the heat resistance of the active material, the degree of drying is 40% or less, preferably 35% or less moisture is advantageous for storage and workability.

In the sustained-release preparation according to the present invention prepared through the above process, the active material is adsorbed at a high concentration on the porous carrier, and once the active material is adsorbed by the carrier structure, the absorption of water is significantly controlled and the moisture inside the carrier is constant. When the limit is reached, the lattice of the polysaccharide matrix is loosened and the active substance is released. When the water content is reduced again, the lattice of the polysaccharide matrix is restored to stop the release of the active substance.

In addition, organic acids and inorganic acids such as phosphorous acid, phosphoric acid, acetic acid, hydrochloric acid, or boric acid added as release regulators prevent the polysaccharides from being rapidly decomposed by bacteria, etc., thereby maintaining the sustained-release membrane durability, while they gradually When released into the microspheres, they release the biologically active substances to the outside through the micro holes generated as they are released.

Hereinafter, the present invention will be described in more detail with reference to the following Examples. These examples are only for illustrating the present invention more specifically, but the scope of the present invention is not limited to these examples. In the following examples, for the sake of convenience, imazaquine, naproamide, metolachlor as biologically active substance, diatomaceous earth as a carrier, curdlan as a polysaccharide, KOH as an inorganic alkali, and a release regulator Phosphoric acid was mainly used.

Pesticide components, carriers, and polysaccharides used in the following examples are merely examples selected for convenience, and the various compounds mentioned above may be applied in the same manner, and two or more pesticide components may be applied to those skilled in the art. something to do.

Preliminary Experimental Example  1 polysaccharide Gelation  Test

2.5 g of curdlan was added to 200 ml of water, and dissolved in 8.3 g of KOH. Then, 2.5, 5.0, and 10.0 g of phosphorous acid (H ₃ PO ₃ ), phosphoric acid (H ₃ PO ₄ ), acetic acid (CH ₃ COOH) and Hydrochloric acid (HCl) was added and thoroughly stirred to measure the respective pH. Each sample was then gelled (FIG. 1). The pH and degree of gelation are shown in Table 1.

As can be seen from the table, when 2.5 g of organic acid is added, the pH reaches 13.1 to 13.3, and when 5 g is added, the pH reaches about 11.7. When 10 g is added, the pH is 3.4 to 5.6 only when phosphoric acid is added. The change was minimal when acetic acid was added.

That is, the degree of gelation was found to be more sensitive to the pH change due to the addition of the organic acid than the amount of the organic acid. That is, for smooth gelation, the pH of the curdlan solution was preferably 12 or less.

Organic acid Addition amount (g) pH Gelation degree Phosphorous acid 2.5 13.2 - 5 13.0 - 10 5.61 Good Phosphoric Acid 2.5 13.1 - 5 11.7 Good 10 3.45 Good Acetic acid 2.5 13.3 - 5 13.2 - 10 5.53 Good Inorganic hydrochloric acid 2.5 12.5 - 5 2.0 Good 10 1.0 Good

Preliminary Experimental Example  2 Biodegradation prevention test of polysaccharides by organic acid 1

(1) It was confirmed whether biodegradation of polysaccharides was delayed by addition of organic acid to starch.

The degree of biodegradation was checked for 18 days at room temperature with respect to the control group to which the phosphoric acid, phosphoric acid and acetic acid was added as an organic acid and the control group not added. Specific compositions of the experimental zones and the results are shown in Table 2.

As can be seen from the table, only the control was biodegraded, confirming that organic acids can significantly delay the biodegradation of polysaccharides.

Starch Other additions Biodegradation degree Control 2.5 g of starch in 100 ml of water Biodegradation Treatment tool 1 2.5 g of starch in 100 ml of water KOH 8.3g, H ₃ PO ₃ 10g Not observed Treatment 2 2.5 g of starch in 100 ml of water H ₃ PO ₃ 10g Not observed Processing Unit 3 2.5 g of starch in 100 ml of water KOH 8.3g, H ₃ PO ₄ 10g Not observed Processing Unit 4 2.5 g of starch in 100 ml of water KOH 8.3g, CH ₃ COOH 10g Not observed

(2) 2.5 g of curdlan was added to 200 ml of water, and the mixture was sufficiently stirred. Then, a control group gelled by heating for 1 minute with ultrasonic waves and 2.5 g of curdlan and 8.3 g of KOH were dissolved in 200 ml of water, followed by H ₃ PO ₃ The degree of biodegradation was observed while the gelled treatment was left at room temperature for 14 days by adding 10 g and ultrasonically heating for 1 minute.

 As a result, as shown in the photograph of FIG. 2, no signs of biodegradation were found in the treatment and the control was confirmed to be significantly biodegradable. From these experiments, it can be seen that organic acids significantly delay the biodegradation of polysaccharides.

(3) Since the sustained release preparations are completely resistant to biodegradation, it may be a problem in use, so that the time for biodegradation under natural conditions, that is, under the condition that the phosphite, which is the contents of the sustained release preparations, may be repeatedly eluted, Experiment.

Phosphorous acid was eluted by leaving the treated tool prepared in (2) in 400 ml of water for 1 hour at intervals of 3 days, and then the treated tool was left to stand at room temperature. After 10 dissolution experiments, signs of biodegradation were found in the treatments.

The sustained release formulation coated with a polysaccharide added an appropriate amount of the organic acid according to the present invention was confirmed that the biodegradation is delayed for a long time in the natural state and finally sustained sustained release.

(4) The time for biodegradation of the coating component of the sustained release preparation according to the present invention under the same conditions as in nature was measured.

2.5 g of curdlan was added to 200 ml of water, and 8.3 g of KOH was added thereto, and the mixture was sufficiently stirred. After heating for 1 minute with ultrasound, gelled control (AC, BC, CC) and 2.5 g of curdlan were placed in 200 ml of water and KOH. After dissolving by adding 8.3 g, organic acids were added in the amounts shown in Table 3 below, and gelled treatments were prepared by heating for 1 minute with ultrasonic waves.

H ₃ PO ₃ (g) H ₃ PO ₄ (g) CH ₃ COOH (g) A1 1.0 A2 0.84 A3 0.78 B1 0.5 B2 0.42 B3 0.39 C1 0.33 C2 0.28 C3 0.26

5 g of each of the prepared control and treatment groups were buried at a depth of 3 cm in the soil collected from the package, and stored in a greenhouse for plant cultivation at 20 to 25 ° C. to check whether they remained after 3 months and 9 months.

After 3 months, the remaining amount of the control and the treatment was shown in the photograph in FIG. As shown in FIG. 3, it can be seen that a significant amount of the treatment groups added with 0.5 g or more of phosphorous acid, 0.42 g or more of phosphoric acid, or 0.39 g or more of acetic acid remain.

After 9 months, no residual amount was observed in all treatments.

Preliminary Experimental Example 4 Model Test of Sustained Release Formulations

Model tests were conducted to visually confirm that the sustained release formulations according to the invention may indeed exhibit sustained release.

As a model of "carrier to which biologically active substance is adsorbed," a preparation containing methyl violet, which is widely used as a dye for agrochemicals, was used. The methyl violet formulation was prepared by adsorbing 0.5 g of methyl violet to 1 kg of sand.

First, 2.5, 5, and 10 g (treated 1, treated 2, and treated 3, respectively) were dissolved in 100 ml of an aqueous solution of 8.3 g of KOH dissolved therein, and 10 g of phosphorous acid was added to each to prepare an active substance solution. 1 kg of methyl violet preparation was added to the solution, stirred evenly, and hot air dried to prepare a sustained release preparation model. Untreated methyl violet formulation was used as a control. The photograph of each formulation is shown in FIG.

100 mg of each treatment formulation was placed in a test tube, and 5 ml of deionized water (DDW) was added thereto for 1 day, followed by recovery for 16 days, and the color change of the recovered water was observed (FIG. 5). In FIG. 5 each test tube is listed by date of recovery.

As can be seen in the photograph shown in Figure 5, the coating-treated formulation can be confirmed that the elution is almost finished after about 9 days of the large amount of methyl violet is eluted from day 1. On the other hand, in the coating liquid treatment groups according to the present invention, it is understood that only a small amount of methyl violet is continuously eluted even when elution amount is small. In particular, the more the content of the curdlan was confirmed that the amount of methyl violet is eluted by the sustained release.

After 16 days, each formulation was recovered and dried to examine the degree of residual color (FIG. 6). Color-coated formulations show that sustained release may occur even after 16 days. The higher the amount of curdlan, the greater the amount of methyl violet remaining, and in the case of the control, the decolorized color shows that most of the methyl violet is eluted.

Preliminary Experimental Example 5 Preparation and Sustained Release Test of Sustained Release Film Containing Active Material

To determine whether the high emulsifiable (hydrophobic liquid) metolachlor (97.8%) is maintained in the curdlan matrix without separate separation after 4 minutes of heat treatment at 102 ° C The formation of the film was tested.

water ^*One Kirdlan ^*2 KOH ^{* 3} H ₃ PO ₄ ^*4 Metola Chlor ^{* 5} H ₃ PO ₄ ^{* 6} After heat treatment matrix ^{* 7} Meto-a 50 ml 0.5g 0.415 g 0.48ml 23.5ml - Separation Meto-b 50 ml 0.5g 0.415 g 0.48ml 47ml - Separation Meto-c 50 ml 0.5g 0.415 g 0.24ml 47ml Separation Meto-d 50 ml 0.5g 0.415 g 0.24ml 23.5ml 0.18ml Original and uniform

To 50 ml of water, curdlan, KOH, phosphoric acid (H ₃ PO ₄ ), metolachlor (97.8%) and phosphoric acid were added in the order and in the amounts shown in Table 4 above, followed by forced stirring, and 20 ml each in glass shale. Followed by heat treatment at 102 ° C. for 4 minutes. In Table 4, Meto-A, Meto-B and Meto-C represent sustained-release preparations prepared by simultaneously mixing phosphoric acid, which is a release regulator, with a biologically active substance, and Meto-D is sustained release of curdlan before the addition of the porous carrier. A sustained release preparation of a biologically active substance according to the invention with a membrane formed.

After the heat treatment, the curdlan matrix and the pesticide raw material metolachlor (97.8%) could be directly identified, and the matrix photograph of each treatment was shown in FIG. 7.

As shown in FIG. 7, the sustained release formulation Meto-D prepared by the method of the present invention did not separate the biologically active agent and the polysaccharide matrix, but Meto-A, B, and C were separated.

Example  One Powder  Active substance In a slow release membrane  Contained Sustained release  Preparation of the formulation

To 200 ml of water, 1.25 g of curdlan, 0.4 g of KOH, and 0.8 ml of aqueous ammonia solution (NH ₄ OH) were added to dissolve it, and then 30.6 g of an acidic pesticide-based imazaquine (98%) was added to adjust the pH of the solution. After stirring with force, 2 ml of phosphoric acid (H ₃ PO ₄ ), a second release controlling agent, was added to sufficiently narrow the gel lattice spacing of the curdlan to prepare an active material solution.

Sustained release of the biologically active substance according to the present invention by homogeneously mixing the solution containing the active substance and 1000 g of dry diatomaceous earth, drying at 100 ° C. to less than about 35% moisture to form a sustained release membrane on the surface of the adsorption carrier. Sex formulations were prepared.

1 g of the above formulation was added to a test tube, and 5 ml of DDW was added thereto for one day, and the recovery was repeated. After the same amount of methanol was added to the recovered sample, 50 μl of each was taken, and the amount of imazaquin in the solution was measured using HPLC. Analyzes (Table 5).

Watering Release amount compared to formulation content (%) One 5.06 2 4.17 3 2.99 4 1.97 5 3.57

Comparative example  One Powder  Active substance In a slow release membrane  Contained Sustained release  Preparation of the formulation

1.25 g of curdlan was added to 200 ml of water, 0.83 g of KOH was dissolved, 0.84 ml of phosphoric acid was added, 30.6 g of imazaquine (98%) was added, and the mixed solution was stirred. The active material solution was prepared without addition.

After the homogeneous mixing of the solution containing the active substance and 1000 g of dry diatomaceous earth was dried to 100% moisture at 100 ℃ to prepare a sustained release formulation.

As a result, the original powder did not contain a substantial portion in the sustained release film matrix, which was not preferable as a method for producing a sustained release formulation.

Comparative example  2 Powder  Active substance In a slow release membrane  Contained Sustained release  Preparation of the formulation

2 g of curdlan and 0.83 g of KOH were dissolved in 200 ml of water, and the pH of the solution was adjusted by adding 0.84 ml of the first release regulator phosphoric acid, and then 30.6 g of imazaquine (98%) was added thereto. Was stirred, and an active material solution was prepared without additional release control agent.

After the homogeneous mixing of the solution containing the active substance and 1000 g of dry diatomaceous earth was dried to 100% moisture at 100 ℃ to prepare a sustained release formulation.

As a result, the original powder did not contain a substantial portion in the sustained release film matrix, which was not preferable as a method for producing a sustained release formulation.

Comparative Example 3 Preparation of Sustained Release Formulation Containing Powdered Active Material in Sustained Release Film

2 g of curdlan and 0.83 g of KOH were dissolved in 200 ml of water, 3.5 ml of 10% phosphoric acid was added, and 30.6 g of imazaquine (98%) was added, followed by stirring the mixed solution. The active material solution was prepared without addition.

After the homogeneous mixing of the solution containing the active substance and 1000 g of dry diatomaceous earth was dried to 100% moisture at 100 ℃ to prepare a sustained release formulation.

As a result, the curdlan content was high and reacted rapidly with phosphoric acid so that the gelation progressed rapidly, so that the original agent and the curdlan coating solution were not sufficiently mixed, which was not preferable as a method for preparing a sustained release formulation.

Comparative example  4 Powder  Active substance Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

To 200 ml of water, 1.25 g of curdlan, 0.4 g of KOH, and 0.8 ml of aqueous ammonia solution (NH ₄ OH) were added to dissolve, and 2 ml of phosphoric acid was added and 30.6 g of imazaquine (98%) was added to the solution, followed by stirring. Was prepared.

After the homogeneous mixing of the solution containing the active substance and 1000 g of dry diatomaceous earth was dried to 100% moisture at 100 ℃ to prepare a sustained release formulation.

 The original agent and curdlan coating liquid were divided separately, which was not preferable as a method for producing a sustained release formulation.

Example 2 Preparation of a Sustained-Release Formulation Containing a Sustained-Release Membrane with Powdered Active Substances Easily Decomposed and Modified by Strong Acids and Strong Alkali

1.25 g of curdlan was added to 200 ml of water, and 0.83 g of KOH was added to dissolve. Then, 2 ml of surfactant was added and 0.36 ml of phosphoric acid (H ₃ PO ₄ ) was added to pH 12 to facilitate agitation of the pesticide raw material. After adjusting to 9, add 32.89 g of naproamide (76%) in the form of raw, evenly forcing stirring, and 1 g of borax as a second release regulator to sufficiently narrow the lattice spacing of the curdlan gel in neutral or weak alkali. The active material solution was prepared by adding thereto.

The homogeneous mixture of the solution containing the active material and 1000 g of dry diatomaceous earth is dried to 100% or less at 100 ℃ moisture to form a sustained-release film on the surface of the adsorbent carrier to release the biologically active material according to the present invention Sex formulations were prepared.

1 g of the above formulation was added to a test tube, and 5 ml of DDW was added to the collected sample. The same amount of methanol was added to the recovered sample, followed by 50 μl of napromide in solution. Was analyzed (Table 6).

Watering Release amount compared to formulation content (%) One 12.33 2 11.64 3 5.86 4 6.08 5 9.30

Comparative example  5 It is easily decomposed and modified with strong acid and strong alkali Powder  Preparation of sustained-release preparations containing the active substance

Dissolve by adding 1.25 g of curdlan and 0.83 g of KOH to 200 ml of water, add 0.84 ml of phosphoric acid (H ₃ PO ₄ ), and add 50 g of pesticide naproamide (93%), and then mix The sustained release formulation was prepared in the same manner as in Example 2, except that the solution was stirred to prepare a biologically active substance solution.

The raw material powder was not contained in the sustained-release film matrix substantially, and thus, it was not preferable for the preparation of the sustained-release preparation.

Comparative Example 6 Preparation of Sustained-Release Formulation Containing Powdered Active Substances Easily Decomposed and Denatured to Strong Acids and Strong Alkali

1.25 g of curdlan and 0.83 g of KOH were dissolved in 200 ml of water, and then 2 ml of surfactant was added and 2 ml of phosphoric acid (H ₃ PO ₄ ) was added for smooth stirring of the pesticide raw material. Adjusted to. To this, 32.89 g of pesticide-based naproamide (76%) was added and stirred evenly, and 1 g of borax (Na ₂ B ₄ O ₇ · 10H ₂ O) was added to sufficiently narrow the lattice spacing of the curdlan gel. A sustained release formulation was prepared in the same manner as in Example 2, except that the solution was prepared.

The solution containing the active substance was curdlan gelled by the addition of a large amount of phosphoric acid, and when the raw agent was added, the solution was not stirred with the gel, which was not preferable as a method for preparing a sustained release formulation.

Example  3 hydrophobic liquid active material Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

1 g of curdlan and 0.83 g of KOH were dissolved in 100 ml of water, and 0.48 ml of half the level of 0.84 ml of phosphoric acid (H ₃ PO ₄ ) to which curdlan gelation proceeded was added to loosen the cudlan lattice, 47 ml of pesticide raw material metolachlor (97.8%) was added thereto, followed by forced stirring, and 0.36 ml of phosphoric acid was added as a second release controlling agent to sufficiently narrow the lattice spacing of the curdlan gel, thereby preparing an active material solution.

The homogeneous mixture of the solution containing the active material and 1000 g of dry diatomaceous earth is dried to 100% or less at 100 ℃ moisture to form a sustained-release film on the surface of the adsorbent carrier to release the biologically active material according to the present invention Sex formulations were prepared.

1 g of the above formulation was added to a test tube, and 5 ml of DDW was added thereto for 1 day, and the recovery was repeated. After the same amount of methanol was added to the recovered sample, 50 μl of each was taken and HPLC was used. The content was analyzed (Table 7).

Watering Release amount compared to formulation content (%) One 2.93 2 4.53 3 4.41 4 4.31 5 3.32

Comparative example  7 Hydrophobic liquid active material Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

1 g of curdlan and 0.83 g of KOH were dissolved in 100 ml of water, 0.84 ml of phosphoric acid (H ₃ PO ₄ ) was added, 47 ml of pesticide raw material metolachlor (97.8%) was added, and then it was evenly stirred by force. The active substance solution was prepared.

After homogeneously mixing the solution containing the active substance and 1000 g of dry diatomaceous earth and drying it to about 35% or less at 100 ° C., raw material flowed out, which was not preferable as a sustained-release preparation method.

Comparative example  8 hydrophobic liquid active material Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

After dissolving by adding 1 g of curdlan and 0.83 g of KOH to 100 ml of water, 0.84 ml of phosphoric acid (H ₃ PO ₄ ) was added, 94 ml of pesticide raw material metolachlor (97.8%) was added, and then it was evenly stirred by force. The active substance solution was prepared.

After homogeneously mixing the solution containing the active substance and 1000 g of dry diatomaceous earth and drying it to about 35% or less at 100 ° C., raw material flowed out, which was not preferable as a sustained-release preparation method.

Comparative example  9 hydrophobic liquid actives Sustained release  Contained in the membrane Sustained release  Preparation of the formulation

After dissolving by adding 1 g of curdlan and 0.83 g of KOH to 100 ml of water, 0.42 ml of phosphoric acid (H ₃ PO ₄ ) was added to half the amount of curdlan gelling and the pesticide raw material metolachlor (97.8%). ) 94 ml was added and forced stirring was carried out to prepare an active material solution.

After homogeneously mixing the solution containing the active substance and 1000 g of dry diatomaceous earth and drying it to about 35% or less at 100 ° C., raw material flowed out, which was not preferable as a sustained-release preparation method.

Application example Sustained release  Pavement Test Of Pesticides

It was confirmed that the sustained release formulation of the biologically active substance prepared according to the method of the present invention prepared in Example 1 exhibited a sustained release effect in actual packaging.

Four sets of 3.3 m ² of each treatment were prepared on the grass two days after mowing, and each set was treated with the relevant substances in the amounts shown in Table 8 below. The control was treated with a sand adsorbent formulation by polyvinyl alcohol (PVA) which is commonly used in granulation pesticide preparation.

Throughput per 3.3m ² Active substance content (mg) Forehead queen Treatment Zone 1 10 g of formulation according to Example 1 300 Control 10 g of PVA adsorbent (dry basis) 300 No treatment No treatment 0

After the treatment of each formulation, the weed development condition was first examined at 60 days and the second final irradiation at 120 days, and the results are shown in Table 9 and Table 10, respectively.

Treatment contents Weeding A B C D E Treatment Zone 1 0 0 0 5 0 Control 10 131 16 15 One No treatment 14 > 1000 > 100 192 24

A: Erigeron annuus D: Chenopidium album

B: Digitaria ciliaris E: Taraxacum platycarpum

C: Panicum bisulcatum

Weeding a b c d e f g h i j Treatment Zone 1 69 4 9 0 0 0 0 0 0 0 Control 592 14 10 4 6 One 124 8 0 0 No treatment 416 0 44 108 0 3 0 6 192 32

a: Luzula capitata f: Equisetum arvense

b: Rumex acetosa g: Kummerowia striata

c: Plantago camtschatica h: Erigeron annuus

d: Setaria glauca i: Trisetum bifidum

e: Ixeris japinica j: Ajuga multiflora

By using the sustained-release preparation according to the present invention, it is possible to effectively control the release time and the release amount for expressing the effect of the pesticide or fertilizer active material. Therefore, the same effect can be obtained even if a high concentration of pesticides or fertilizers are not repeatedly added in a short cycle.

When the sustained-release preparation containing the pesticide or fertilizer according to the present invention as an active material can be controlled by controlling the amount of water, the time of watering or the number of watering, etc. to control the time of expression of the effect of the pesticide or fertilizer active material in agriculture, pesticide or fertilizer Not only can it significantly reduce the amount of use and work loss, but it also has little risk of weakening and can have a positive effect on environmental preservation and clean production of pesticides or fertilizers.

Claims (12)

1) 0.05 to 15 parts by weight of a polysaccharide and 0.3 to 20 parts by weight of an inorganic alkali are added to the base solvent with respect to 1000 parts by weight of the porous carrier, and a first release controlling agent is added to adjust the pH of the solution to 12 to 9 Adding 0.0005 to 150 parts by weight of a biologically active substance of agitation, adding a second release controlling agent so that the pH of the total solution is 9 or less, and preparing the active substance solution; And 2) sustained release of the biologically active material comprising the step of homogeneously mixing the active material solution obtained in step 1) with 1000 parts by weight of the porous carrier and drying at a temperature of 25 to 150 ℃ Method for preparing sex preparations. The method of claim 1 wherein the base solvent is selected from water, alcohols, acetone, acetonitrile, dioxane, dimethylformamide, dimethylsulfoxide, tetrahydrofuran or mixtures thereof. The method of claim 2 wherein the base solvent is water. The method of claim 1 wherein the biologically active substance is poorly soluble. The method according to claim 1, wherein the biologically active substance is an insecticide, herbicide, plant growth regulator, nematicide, fungicide, fungicide, rodenticide, fumigant, animal and pest control agent, biopesticide, pheromone, sex attractant, flavorant, fragrance , A dietary supplement, a drug and a fertilizer selected from the group consisting of fertilizers. The method of claim 5, wherein the biologically active substance is a phosphite, acephate, Isoxathion, Imidacloprid, Ethylthiodemeton, Ethofenprox, Vita Bitalin, Cartap, Carbosulfan, Copenpentezine, Cyclopyrifas-methyl, Fenbutatin-oxide, Cycloloprine ), Dimetylrinphos, Dimethoate, Dimethoate, Silafluofen, Diazinon, Thiodicarb, Thiocyclam, Tebufenozide, Nitenpyram, Vamidothion, Bifenthrin, Pyridaphenthion, Pyridaben, Pyrimiphos-methyl, Fipronil ), Phenisobromolate, Buprofezin, Furatoca Furathiocarb, Propafos, Bensultap, Benfuracarb, Formothion, Marathon, Monocrotophos, BPMC, CVMC, DEP, EPN, MEP, MIPC, MPP, MTMC, NAC, PAP, PHC, PMP, XMC, Acibenzolar-S-methyl, Azoxystrobin, Isoprothiolane, Isoprothiolane, Isoprodion, Iminoctadine triacetate, Oxolinic acid, Oxyquinocopper, Kasugamycin, Carpropamid, Captan, Diclomezine ), Thiabendazole, Thifluzamide, Tecloftalam, Tricyclazole, Validamycin, Hydrodroxyisoxazole, Pyroquilon ), Fenarimol, Ferrimzone, Fthalide, Blasticidin, Polyoxin ), Metasulfocarb (Methasulfocarb), Metalaxil (Metalaxl), Metalaxyl-M, Metominostrobin, Mepronil, Ampronil, Ampicillin, CNA, IBP, DF-351, NNF -9425, NNF-9850, Azimsulfuron, Atrazine, Amethrin, Inabenfide, Imazosulfuron, Uniconazole, Espprocarb (Esprocarb), Etobenzanid, Oxadiazon, Carfenstrole, Quizarofop-ethyl, Quinclorac, Cumylron, Clomelo Chlomethoxynil, Cyclosulfamuron, Dithiopyr, Cinosulfuron, Cyhalofop-butyl, Simazine, Dimethametryn, Dimepiperate, Cinmethylin, Dymron, Thenylchor, Triapenthenol, Naproanilide , Paclobutrazol, Bifenox, Piperophos, Pyrazoxyfen, Pyrazosulfuron-ethyl, Pyrazolate, Pyrazolate (Pyributicarb), Pyriminobac-methyl, Butachlor, Butamifos, Pretilachlor, Bromobutide, Bensulfuron-methyl, Bensulfuron-methyl, Benzofenap, Bentazon, Benthiocarb, Pentoxazone, Benfuresate, Mefenacet, Molinate, Jasmonic Acid, Salicylic Acid , BABA, BTH, ACN, CNP, 2,4-D, MCPB, MCPBethyl, imazaquine, naproamide and metolachlor. The method of claim 1, wherein the polysaccharide is festan, levan, xantham gum, pullulan, polysaccharide-7, cellulose, juglan, gellan, curdlan or combinations thereof. The method of claim 1 wherein the inorganic alkali is KOH, NaOH, NH ₄ OH or a combination thereof. 2. The method of claim 1, wherein in step 1) a biologically active substance in its original form is additionally added with a surfactant. The method of claim 1, wherein the porous carrier is zeolite, pearlite, vermiculite, diatomaceous earth, ceramic, activated carbon, sand, white carbon, bentonite or mixtures thereof. The method of claim 1 wherein the release controlling agent is an organic or inorganic acid. 12. The method of claim 11, wherein the release controlling agent is selected from phosphorous acid, phosphoric acid, acetic acid, hydrochloric acid, boric acid, or mixtures thereof.

Images