WO2025084484A1 - Sustained-release formulation and preparation method therefor - Google Patents

Abstract

Disclosed are a sustained release formulation and a method for preparing same, wherein the sustained release formulation contains a biologically active substance that repels insects or animals, thereby preventing their approach. To this end, the present invention provides a sustained release formulation comprising: a three-dimensional body fired by heating a powder molding material molded into a predetermined shape; and a surface coating layer provided on the surface of the three-dimensional body and formed by sintering a mixture of a matrix material, a biologically active material, a release control agent, and a solvent. According to the present invention, the release time and release amount for expressing the effect of the biologically active substance can be effectively controlled, and thus the approach of a target insect or animal can be blocked over a long period of time.

Description

SUSTAINED RELEASE FORMULATION AND MANUFACTURING METHOD THEREOF

The present invention relates to a sustained-release preparation containing a biologically active substance and a method for producing the same, and more specifically, to a sustained-release preparation containing a biologically active substance repelled by insects or animals and capable of blocking the approach of insects or animals, and a method for producing the same.

Representative pests that mainly occur in stored agricultural products such as rice weevils and grain borers are known to be the biggest causes of lowering the quality of rice. When these pests occur in rice storage containers, they rapidly reproduce, consuming nutrients in the rice and releasing excrement, thereby lowering the quality of the rice. Molds such as yellow mold fungi and bacteria reproduce in rice storage containers when affected by humidity and temperature, accelerating the decline in rice quality.

In addition, due to the recent increase in imported agricultural products, foreign pests have been introduced into the country, causing massive damage.

Fumigants such as methyl bromide, aluminum phosphide, and chlorpicrin are used as pesticides to control pests occurring in stored agricultural products, and are used for quarantine of imported agricultural products. However, the pesticides mentioned above are organic synthetic pesticides, so they have problems such as residual toxicity, adverse effects on the human body, and increased resistance in various pest species.

Recently, various attempts have been made to use plant-based essential oils extracted from natural products as pesticides to solve the problems of organic synthetic pesticides as mentioned above.

That is, various plant extracts and plant essential oils exhibit ovicidal, repellent, and insecticidal activities against pests in stored agricultural products. For example, the essential oil of safflower is known to have bactericidal activity against red bean weevils, rice weevils, and mealybugs.

In addition, folk remedies were used to control pests by putting whole garlic, red pepper, charcoal, etc. in storage containers such as rice bins to preserve the quality of stored agricultural products, but the pest control effect was not that great.

By improving the aforementioned folk remedy, a product formulated with plant-based essential oil ingredients was prepared, in which the allicin ingredient extracted from garlic and the capsaicin ingredient extracted from red pepper were contained in a synthetic resin breathable container and used as a quality preservative for rice. However, the plant-based essential oil is a volatile substance, and the insecticidal activity is mainly achieved through the fumigation action of the volatilized insecticidal ingredient, so there is a problem in that the effective ingredient rapidly evaporates in a short period of time, and the insecticidal effect is not continuous.

Accordingly, there is a need for the development of a sustained-release formulation that can maintain a continuous insecticidal effect by suppressing rapid volatilization of vegetable essential oils and controlling the release rate.

Recently, a method has been reported in which these plant-based essential oils are encapsulated in polymer microcapsules and used as a pesticide with a continuous insecticidal effect. However, this method has economic problems due to the complex manufacturing process and high production costs.

Accordingly, the first object of the present invention is to provide a sustained-release preparation capable of blocking the approach of various insects, reptiles such as snakes, and mammals by coating the surface of a sintered body manufactured using a powder molding material with a mixture containing a biologically active substance.

In addition, the second object of the present invention is to provide a method for producing a sustained-release preparation capable of releasing a biologically active substance at a desired rate so that the target insect or animal does not approach for a long period of time.

In order to achieve the first object of the present invention described above, in one embodiment of the present invention, a sustained-release preparation is provided, which comprises a solid formed by heating and firing a powdery molding material formed into a predetermined shape, and a surface coating layer formed on the surface of the solid and fired with a mixture of a matrix material, a biologically active substance, a release-controlling agent, and a solvent.

In addition, in order to achieve the second object of the present invention, one embodiment of the present invention provides a method for manufacturing a sustained-release formulation, including a molding step of molding a powdery molding material into a predetermined external shape, a first firing step of heating the molded powdery molding material to create a three-dimensional shape, a coating step of immersing the three-dimensional shape in a mixture of a matrix material, a biologically active substance, a release-controlling agent, and a solvent to coat the mixture on the surface of the three-dimensional shape, and a second firing step of heating the mixture coated on the three-dimensional shape to form a surface coating layer.

According to the present invention, since the release time and release amount for the expression of the effect of a biologically active substance can be effectively controlled, the approach of target insects or animals can be blocked for a long period of time.

In addition, the present invention can provide a sufficient access-blocking function for insects, reptiles such as snakes, and mammals because the biologically active substance is exposed on the surface instead of being located inside the powdery molding material even when the biologically active substance is used, and the amount of the biologically active substance used compared to the powdery molding material can be minimized, thereby reducing the manufacturing cost.

In addition, the present invention enables stable and efficient production of sustained-release preparations since no decomposition products are generated even when an active substance that is easily decomposed is used.

Figure 1 is a cross-sectional view illustrating a sustained-release formulation according to the present invention.

Figure 2 is a flow chart for explaining a method for manufacturing a sustained-release formulation according to the present invention.

Hereinafter, with reference to the attached drawings, a sustained-release formulation and a method for manufacturing the same according to preferred embodiments of the present invention will be described in detail.

Figure 1 is a cross-sectional view illustrating a sustained-release formulation according to the present invention.

Referring to FIG. 1, the sustained-release formulation according to the present invention includes a solid (100) formed by firing a powdery molding material, and a surface coating layer (200) formed by coating the surface of the solid (100) with a mixture containing a biologically active substance (210) and then firing the mixture.

Specifically, the sustained-release preparation of the present invention may be composed of 5 to 40 wt% of the solid (100) and 60 to 95 wt% of the mixture based on 100 wt% of the total. At this time, if the content of the solid (100) is less than 5 wt%, the durability of the solid (100) may be reduced and the release rate of the biologically active substance (210) may be accelerated more than a predetermined rate, which may cause a problem. If the content of the solid (100) exceeds 40 wt%, the content of the biologically active substance (210) may be insufficient relative to the size of the sustained-release preparation.

In these sustained-release preparations, the biologically active substance (210) is not only adsorbed onto the porous solid (100), but is also uniformly incorporated into the sustained-release film formed on the surface of the solid (100) by the matrix material, and the biodegradation of the sustained-release film is suppressed for a considerable period of time in a dry state, and then the biodegradation of the sustained-release film progresses according to the amount of moisture absorbed, gradually releasing the biologically active substance (210), and when the moisture absorbed in the sustained-release film evaporates, the sustained-release film closes and the release of the biologically active substance (210) stops.

Below, each component is described in more detail with reference to the drawings.

Referring to Figure 1, the sustained-release formulation according to the present invention includes a stereostructure (100).

The above-mentioned solid (100) is formed by heating and firing a powdery molding material formed into a pre-designated shape such as a sphere to remove internal impurities and to make the internal condition the best possible, and not only provides a space in which a mixture containing a biologically active substance (210) can be coated, but also provides a space in which the biologically active substance (210) can be adsorbed. At this time, the sphere can be formed into a sphere having a diameter of 1 mm to 30 mm.

As the above-mentioned powder molding material, any one of alumina, zeolite, chitosan, natural clay, kaolin, pyrophyllite, bentonite, monnorillonite, diatomaceous earth, calcium carbonate, zinc oxide, lacquer, zirconia, magnesium, lime, white clay, silica, talc, and strontium may be used, and it is preferable to use alumina, zeolite, zinc oxide, lacquer, or chitosan.

In addition, it is preferable to use powder having a diameter of 100 to 500 ㎛ as the powder molding material, and a molded body can be formed by mixing 65 to 90 wt% of the powder molding material and 10 to 35 wt% of water.

The firing of the above-mentioned solid (100) can be performed at 700 to 900°C. At this time, if the firing temperature of the solid (100) is lower than 700°C, a problem of reduced durability of the solid (100) may occur, and if the firing temperature of the solid (100) exceeds 900°C, a problem of reduced effectiveness of the active material may occur.

Referring to FIG. 1, the sustained-release formulation according to the present invention includes a surface coating layer (200).

The above surface coating layer (200) is provided on the surface of the solid (100), and is composed of a mixture containing a matrix material, a biologically active material (210), a release control agent, and a solvent, and is heated and fired. If necessary, the surface coating layer (200) can be fired by heating after naturally drying the mixture coated on the surface of the solid (100) in a shaded place for 4 to 6 hours.

The matrix material constituting the surface coating layer (200) according to the present invention provides adhesiveness to prevent the surface coating layer (200) from being peeled off from the solid (100), and may be composed of a natural polymer, a cellulose derivative, or a mixture thereof. In addition, the matrix material forms a sustained-release film on the surface of the solid (100) to suppress the release of biologically active substances (210).

In this way, the release of the biologically active substance (210) is primarily suppressed by the adsorption property of the pore-formed solid (100), and secondarily suppressed by the sustained-release film formed on the surface of the solid (100) by the matrix material.

The above natural polymers may include tapioca, wheat, seaweed, agar, seaweed, sweet potato, corn, potato, sea squirt, or mixtures thereof.

As the cellulose derivative, hydrolyzed starch, starch derivative, maltodextrin, hydroxypropyl methylcellulose, polyvinylpyrrolidone, chitin, chitosan, polyethylene glycol, gelatin, solubilized protein, polyacrylamide, polyamine, polyvinyl alcohol, lignin, xanthan gum, guar gum, paraffin wax, 3-methacryloxypropyltrimethoxysilane, hexamethyldisilazane or a mixture thereof can be used.

Meanwhile, the matrix material may be added in an amount of 5 to 35 wt% based on 100 wt% of the mixture. At this time, if the content of the matrix material exceeds the threshold, a problem may occur in which the release rate of the biologically active substance (210) becomes faster or slower than a pre-specified rate.

The biologically active material (210) constituting the surface coating layer (200) according to the present invention may be an insecticide, a disinfectant, an essential oil, or a mixture thereof, which is a repellent that is disliked by the target insects or animals, so as to block the approach of the target insects, reptiles such as snakes, or mammals.

These biologically active substances (210) can be added to the mixture in the original form regardless of hydrophobicity or hydrophilicity, and can exist in the pores formed in the solid (100) and the surface coating layer (200) through the coating process of the mixture, respectively. At this time, the original form means a solid or liquid form in the manufactured state that is not dissolved in a solvent.

The above bactericidal and insecticidal agents include tetradecadienyl acetates, caprylic acid, chloroxylenol, lavender oil, ethylbutylaminopropionate, hydrogenated light paraffin oil, hydrogenated intermediate refined oil, hinokitiol, citronella oil, clove oil, castor oil, spearmint oil, linear alkylbenzenes, transfluthrin, dipropylene glycol, empenthrin, methylenebis, butyl, ethylphenol, alpha-bromocinnamaldehyde, bromfenvinfos, allyl isothiocyanate, iodine, propynyl butyl Propynyl butyl carbamate, di-tert-butyl-p-cresol, hydrotreated light refined oil, naphthalene, camphor, cinnamon oil, mustard seed oil, ethanol, propane, isobutane, peppermint oil, citronella oil, lemongrass oil, soybean oil, paraffin oil, castor oil, cedar oil, rosemary oil, geranium oil, neem oil, orange peel oil, neroli oil, etc. can be used.

The above bactericidal and insecticidal agents include piperonyl butoxide, naphthalene, methyl formate, pyrethrins, pralethrin, phenothrin, diflubenzuron, cyphenothrin, cypermethrin, permethrin, decamethrin, a-Cypermethrin, hydramethylnon, imiprothrin, lambda-cyhalothrin, fipronil, imidacloprid, dinotefuran, metofluthrin, sodium nitrite, diethyltorumide, icaridin, paramenthane-3.8-diol, ethylbutyl Acetylaminopropionate, etc. can be used.

The essential oils that can be used include citronella extract, tea tree extract, lavender extract, eucalyptus extract, lemon extract, coconut extract, geranium extract, cypress extract, basil extract, balsam extract, cassia seed extract, houttuynia cordata extract, capsaicin extract, pine essential oil, sandalwood extract, safflower extract, garlic extract, linalool, clove oil, fennel oil, mugwort, sandalwood, pepper, arsenic, sulfur, etc.

Meanwhile, the biologically active material (210) may be added at 25 to 40 wt% based on 100 wt% of the mixture. At this time, if the content of the biologically active material (210) is less than 25 wt%, a problem may arise in which the effect of blocking the approach of insects or animals is reduced, and if the content of the biologically active material (210) exceeds 40 wt%, a problem may arise in which the release speed becomes faster than a pre-specified speed.

The release-controlling agent constituting the surface coating layer (200) according to the present invention controls the release rate of the biologically active substance (210) attached to the solid (100) by the matrix material so that the biologically active substance (210) is released to the outside, thereby preventing the sustained-release film from being rapidly decomposed by bacteria, etc., thereby maintaining the durability of the sustained-release film, and promoting the release of the biologically active substance (210) to the outside through the microscopic holes created as the biologically active substance (210) is released to the outside.

These release-controlling agents may include inorganic acids, inorganic bases, organic acids, or mixtures thereof.

More specifically, the inorganic acids that can be used include hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, boric acid, carbonic acid, hydrofluoric acid, hydrobromic acid, perchloric acid, and hydroiodic acid.

As the above inorganic base, sodium hydroxide, potassium hydroxide, ammonium hydroxide, magnesium hydroxide, hydroxyapatite, etc. can be used.

The organic acids that can be used include lactic acid, acetic acid, formic acid, citric acid, uric acid, oxalic acid, malic acid, and tartaric acid.

Meanwhile, the release control agent may be added in an amount of 20 to 35 wt% based on 100 wt% of the mixture. At this time, if the content of the release control agent is less than 20 wt%, a problem may occur in which the release speed of the biologically active material (210) becomes slower than a pre-specified speed, and if the content of the release control agent exceeds 35 wt%, a problem may occur in which the release speed becomes faster than a pre-specified speed.

The solvent constituting the surface coating layer (200) according to the present invention plays a role in stably dispersing the matrix material, the biologically active material (210), and the release control agent by mixing them. Distilled water, ethanol, methanol, acetone, benzyl alcohol, hydrogen peroxide, boric acid, PEG, chloroform, etc. can be used as such solvent.

These solvents may be added in an amount of 5 to 25 wt% based on 100 wt% of the mixture. At this time, if the content of the solvent is less than 5 wt%, a problem may occur in which the release rate of the biologically active material (210) becomes slower than a pre-specified rate, and if the content of the release control agent exceeds 25 wt%, a problem may occur in which the surface coating layer (200) is easily detached from the solid (100).

The firing of the surface coating layer (200) may be performed at 80 to 130°C. At this time, if the firing temperature of the surface coating layer (200) is less than 80°C, the firing time of the surface coating layer (200) may increase, which may form an uneven surface on the solid (100), and if the firing temperature of the solid (100) exceeds 130°C, the function of the biologically active material provided in the surface coating layer (200) may be reduced, which may cause a problem.

These mixtures can be mixed at 300 to 1,100 RPM by putting the matrix material, biologically active material (210), release control agent, and solvent into a mixer.

In addition, the surface coating layer (200) may be formed to have a thickness of 10 ㎛ to 300 ㎛ so as to provide a function of blocking the approach of insects or animals, which are the intended targets. At this time, if the surface coating layer (200) is formed to a thickness of less than 10 ㎛, a problem may arise in that it is not possible to provide a biologically active substance (210) sufficient to block the approach of insects or animals, which are the intended targets, and if the surface coating layer (200) is formed to a thickness exceeding 300 ㎛, there is no significant change in the insect or animal avoidance function, but only an increase in the production cost occurs.

The above-mentioned Western-style formulation can be ground to about 100 to 300 mesh and used as a coating agent for natural fibers and synthetic fibers.

Figure 2 is a flow chart for explaining a method for manufacturing a sustained-release formulation according to the present invention.

Referring to FIG. 2, the method for manufacturing a sustained-release formulation according to the present invention includes a molding step (S100) of molding a powdery molding material into a predetermined shape, a first firing step (S200) of heating the molded powdery molding material to create a solid (100), a coating step (S300) of immersing the solid (100) in a mixture containing a biologically active substance (210) to coat the mixture on the solid (100), and a second firing step (S400) of heating the mixture coated on the solid (100) to form a surface coating layer (200).

In the above molding step (S100), a pre-fabricated molding tool is used to mold a powder molding material into a pre-specified external shape, such as a spherical structure.

In the first firing step (S200) described above, the powdery molding material formed through the molding step (S100) is put into a firing device such as a furnace, and then the powdery molding material formed through the firing device is heated to 700 to 900°C to fire a three-dimensional shape (100).

In the above coating step (S300), the solid (100) created through the first firing step (S200) is immersed in a mixture containing a matrix material, a biologically active substance (210), a release control agent, and a solvent, and the mixture is coated on the solid (100) to a thickness of 40 ㎛ to 400 ㎛.

In the above-mentioned second firing step (S400), the mixture coated on the solid (100) through the above-mentioned coating step (S300) is dried in the shade for 4 to 6 hours, and then heated at 50 to 130°C for 30 to 60 minutes to form a surface coating layer (200) fired to a thickness of 30 ㎛ to 300 ㎛ on the surface of the solid (100).

For example, the second firing step (S400) heats the mixture coated on the solid (100) at 50°C for 60 minutes, or heats the mixture coated on the solid (100) at 130°C for 30 minutes to form a surface coating layer (200) on the surface of the solid (100).

At this time, if the firing time of the surface coating layer (200) is less than 30 minutes, a problem of the surface coating layer (200) being peeled off from the solid (100) as the period of use elapses may occur, and if the firing time exceeds 60 minutes, a problem of the color of the surface coating layer (200) becoming dark may occur.

Since the detailed components included in the above-described sustained-release formulation are used in the molding step (S100), the first firing step (S200), the coating step (S300), and the second firing step (S400), overlapping content is omitted.

In addition, the sustained-release preparation manufactured by the above method can be used by coating natural fibers or synthetic fibers after additionally performing the step of grinding to about 100 to 300 mesh.

Although the present invention has been described above with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various modifications and changes may be made to the present invention without departing from the spirit and scope of the present invention as set forth in the claims below.

Claims (7)

A three-dimensional object formed by heating a powdered molding material formed into a predetermined shape; and A sustained-release preparation comprising a surface coating layer formed on the surface of the above-mentioned three-dimensional body and calcined with a mixture of a matrix material, a biologically active substance, a release-controlling agent, and a solvent. In the first paragraph, The above solid is fired at 700 to 900°C, A sustained-release preparation characterized in that the surface coating layer is fired at 80 to 130°C. In the first paragraph, A sustained-release preparation characterized in that the above-mentioned powdery molding material is alumina, zeolite, zinc oxide, lacquer, or chitosan. In the first paragraph, the matrix material A sustained-release preparation characterized by being a natural polymer, a cellulose derivative, or a mixture thereof. In the first paragraph, the biologically active substance A sustained-release preparation characterized by being an insecticide, a fungicide, an essential oil, or a mixture thereof. In the first paragraph, the release control agent A sustained-release preparation characterized by being an inorganic acid, an inorganic base, an organic acid, or a mixture thereof. A molding step for molding a powder-shaped molding material into a pre-specified shape; The first firing step of heating the molded powder molding material to create a three-dimensional shape; A coating step of immersing the above-mentioned solid in a mixture of a matrix material, a biologically active substance, a release-controlling agent, and a solvent to coat the mixture on the surface of the above-mentioned solid; and A method for producing a sustained-release formulation, comprising a second firing step of heating the mixture coated on the above three-dimensional surface to form a surface coating layer.

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