Soybean extract contains particles

Abstract

Because soybean extract is highly water-repellent, it is difficult to granulate, and as granulation progresses, it adheres to the inside of the granulator, requiring cleaning and removal of the adhered material, resulting in poor granule production efficiency. [Solution] The granules contain soybean extract, emulsifier, dextrin, and cyclodextrin.

Description

Technical Field

[0001] The present invention relates to a granulation technique for granules containing soybean extract.

Background Art

[0002] As a solid preparation for dialysate that can reduce the amount of acetic acid and be manufactured without adhesion to the granulator during the manufacturing stage, a solid preparation for dialysate containing an electrolyte, sodium acetate, citric acid, and glucose, and having a specific acetate ion concentration, is known (Patent Document 1). As a manufacturing method that can suppress adhesion to the granulator body during the mixing and granulation of irbesartan, a method is known in which a mixture containing irbesartan at a specific concentration, hypromellose, croscarmellose sodium, and a diluent, and without an anti-adhesion agent, is mixed and granulated using a water / ethanol mixture as a binding solution (Patent Document 2). As a granular pharmaceutical composition that has less adhesion of granules to the inside of the equipment during granulation, a granular pharmaceutical composition is known in which a waxy substance is heated and melted, clopidogrel sulfate, and synthetic aluminum silicate or hydrated silicon dioxide are dispersed or dissolved in it, and then the dispersion or solution is spray granulated (Patent Document 3). As nonionic surfactant-containing particles that suppress adhesion to granulators during manufacturing, nonionic surfactant-containing particles containing specific amounts of nonionic surfactant, water-soluble inorganic powder, aluminosilicate powder, and water-poorly soluble carbonate powder are known (Patent Document 4). As a granular detergent composition that can prevent adhesion to granulators when manufacturing detergent particles containing a large amount of nonionic surfactant over a long period of time, a granular nonionic detergent composition containing a nonionic surfactant, polyalkylene glycol, and an organic chelate builder is known (Patent Document 5). As a method for manufacturing detergent using a granulator having a stirring shaft to prevent detergent aggregates from adhering to the stirring blades, the inner wall and bottom gaps of the stirring device during granulation, a method for manufacturing high bulk density granular detergent is known in which silicon dioxide and aluminosilicate are pre-added and mixed into the device as anti-adhesion agents to spray-dried detergent particles (Patent Document 6). A high bulk density granular detergent composition containing an anionic surfactant paste, a salt of carbonic acid or bicarbonate and potassium, a crystalline aluminosilicate, silica-based powder or clay-based powder is known that can reduce adhesion to the granulator, which is a problem when producing detergent compositions containing a high concentration of anionic surfactant using a stirring or mixing granulation method, and enables stable production (Patent Document 7). [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] Japanese Patent Publication No. 2017-052741 [Patent Document 2] Japanese Patent Publication No. 2016-204305 [Patent Document 3] Japanese Patent Publication No. 2014-132022 [Patent Document 4] Japanese Patent Publication No. 2007-211169 [Patent Document 5] Japanese Patent Application Publication No. 11-006000 [Patent Document 6] Japanese Patent Application Publication No. 07-133498 [Patent Document 7] Japanese Patent Application Publication No. 07-179898 [Overview of the Initiative] [Problems that the invention aims to solve]

[0004] Because soybean extract is highly water-repellent, it is difficult to granulate, and as granulation progresses, it adheres to the inside of the granulator, requiring cleaning and removal of the adhered material, resulting in poor granule production efficiency. [Means for solving the problem]

[0005] The main components of this invention are as follows: 1. Granules containing soybean extract, emulsifier, dextrin, and cyclodextrin. 2. The granules according to 1, which contain 0.1% to 1% by mass of an emulsifier relative to the granules. 3. Granules as described in 1. or 2., wherein the HLB of the emulsifier is 7 or more and 18 or less. Tablets containing granules as described in any of sections 4.1 to 4.3. [Effects of the Invention]

[0006] When granulating soybean extract, which has strong water repellency, it is possible to suppress the adhesion of raw materials inside the granulator, reduce the frequency of cleaning and removal of adhered materials, and enable efficient granule production. [Modes for carrying out the invention]

[0007] The granules of the present invention contain soybean extract, emulsifier, dextrin, and cyclodextrin.

[0008] In the present invention, the soybean extract may be not only soybean extract, but also fermented soybean extract, soy isoflavones, or soy isoflavone aglycones. Examples of soybean extracts include soybean extract, soybean germ extract, and soybean hypocotyl extract. Examples of fermented soybean extracts include fermented soybean extract, fermented soybean germ extract, and fermented soybean hypocotyl extract.

[0009] Soybean extract is, for example, an extract obtained from soybean seeds by an extraction process using a known method. Examples of extraction solvents include water and ethanol. Soybean extract contains soy isoflavones and saponins as active ingredients. Alternatively, the extract may be obtained by increasing the concentration of soy isoflavone aglycones through a hydrolysis operation during the extraction process.

[0010] Soybean germ extract is an extract obtained, for example, from the germ portion of soybean seeds by an extraction process using a known method. Examples of extraction solvents include water and ethanol. Soybean germ extract contains soy isoflavones and saponins as active ingredients. Alternatively, the extract may be obtained by increasing the concentration of soy isoflavone aglycones through a hydrolysis operation during the extraction process.

[0011] Soybean hypocotyl extract is an extract obtained, for example, from the hypocotyl portion of soybean seeds by an extraction process using a known method. Examples of extraction solvents include water and ethanol. Soybean hypocotyl extract contains soy isoflavones and saponins as active ingredients. Alternatively, the extract may be obtained by increasing the concentration of soy isoflavone aglycones through a hydrolysis operation during the extraction process.

[0012] Fermented soybean extract is obtained by fermenting soybeans with microorganisms such as Aspergillus (e.g., koji mold), Bacillus (e.g., natto bacteria), Lactococcus (e.g., Lactococcus garvier), Streptococcus (e.g., Streptococcus intermedias, Streptococcus constellatus), and Bacteroides (e.g., Bacteroides ovatus), and then extracting the fermented soybeans using a known extraction method. Examples of extraction solvents include water and ethanol. Fermented soybean extract contains equol, daidzeins, genisteines, glyciteins, etc. Furthermore, the fermented soybean extract may be obtained by first extracting soybeans using a known extraction method, in which case water or ethanol is used as the extraction solvent, and then fermenting the soybean extract with microorganisms of the genus Aspergillus such as Aspergillus koji mold; microorganisms of the genus Bacillus such as Bacillus natto bacillus; microorganisms belonging to the genus Lactococcus such as Lactococcus garvier; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedias and Streptococcus constellatus; and microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus.

[0013] Fermented soybean germ extract is obtained by fermenting soybean germ with microorganisms such as Aspergillus (e.g., Aspergillus koji mold), Lactococcus (e.g., Lactococcus garvier), Streptococcus (e.g., Streptococcus intermedias, Streptococcus constellatus), and Bacteroides (e.g., Bacteroides ovatus), and then extracting the fermented soybean germ using a known extraction method. Examples of extraction solvents include water and ethanol. Fermented soybean germ extract contains equol, daidzeins, genisteines, glyciteins, and the like. Furthermore, the fermented soybean germ extract may be obtained by first extracting soybean germ using a known extraction method, in which case water or ethanol may be used as the extraction solvent, and then fermenting the soybean germ extract with microorganisms of the genus Aspergillus such as Aspergillus koji mold; microorganisms belonging to the genus Lactococcus such as Lactococcus garvier; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedias and Streptococcus constellatus; and microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus.

[0014] Fermented soybean hypocotyl extract is obtained by fermenting soybean hypocotyls with microorganisms of the genus Aspergillus, such as Aspergillus koji mold; microorganisms of the genus Lactococcus, such as Lactococcus garvier; microorganisms of the genus Streptococcus, such as Streptococcus intermedias and Streptococcus constellatus; and microorganisms of the genus Bacteroides, such as Bacteroides ovatus. The fermented soybean hypocotyls are then extracted using a known method. Examples of extraction solvents include water and ethanol. Fermented soybean hypocotyl extract contains equol, daidzeins, genisteines, glyciteins, and the like. Furthermore, the fermented soybean hypocotyl extract is obtained by first extracting soybean hypocotyls through an extraction process, which is a known method. In this process, as the extraction solvent, for example, water or ethanol is used. Then, the soybean hypocotyl extract is fermented with microorganisms such as Aspergillus genus microorganisms like Aspergillus oryzae; Lactococcus genus microorganisms such as Lactococcus garvieae; Streptococcus genus microorganisms such as Streptococcus intermedicus and Streptococcus constellatus; and Bacteroides genus microorganisms such as Bacteroides ovatus to obtain a fermented product of the soybean hypocotyl extract.

[0015] Soybean isoflavones are isoflavones contained in soybeans and are also called phytoestrogens. They are known to have various physiological effects such as female hormone-like effects, antioxidant effects, anti-hemolytic effects, anti-cholesterol effects, anti-lipemia effects, and antibacterial effects. As soybean isoflavones, three types of aglycones (isoflavone aglycons), namely genistein, daidzein, and glycitein, and three types of glycosides (genistin, daigin, and glycitin), acetylated forms of the glycosides, and malonylated forms are known. Soybean fermented foods such as miso and natto contain a large amount of soybean isoflavone aglycones, but in most cases, they exist as soybean isoflavone glycosides in foods.

[0016] Soybean isoflavone aglycones refer to three types of aglycones, namely genistein, daidzein, and glycitein, which are non-glycosides among the isoflavones contained in soybeans.

[0017] The preferred blending amount of the soybean extract is 10% to 70% by mass in the granules.

[0018] Examples of the emulsifier include nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, polymeric surfactants, and the like. As the emulsifier, nonionic surfactants are preferred, and the HLB of the nonionic surfactant is preferably 7 to 18. Among the nonionic surfactants, sucrose fatty acid esters are preferred. Commercially available products include Ryoto Sugar Ester S-770 (HLB about 7), S-970 (HLB about 9), S-1170 (HLB about 11), S-1570 (HLB about 15), S-1670 (HLB about 16) (manufactured by Mitsubishi Chemical Corporation), and the like. When using a nonionic surfactant as the emulsifier, its HLB is preferably 7 or more and 18 or less, and particularly preferably 14 or more and 18 or less. As the emulsifier, sucrose fatty acid esters are particularly preferred. The blending amount of the emulsifier is preferably 0.1% by mass or more and 1% by mass or less based on the granules.

[0019] Dextrin is a decomposition product obtained by hydrolyzing starch with an acid or an enzyme. The blending amount of dextrin is preferably 0.1% by mass or more and 5% by mass or less based on the granules.

[0020] Cyclodextrin is a kind of cyclic oligosaccharide in which several molecules of D-glucose are bonded by α-1,4 glycosidic bonds to form a cyclic structure. The one in which 6 molecules of D-glucose are bonded is called α-cyclodextrin (α-CD), the one in which 7 molecules are bonded is called β-cyclodextrin (β-CD), and the one in which 8 molecules are bonded is called γ-cyclodextrin (γ-CD). The blending amount of cyclodextrin is preferably 10% by mass or more and 60% by mass or less.

[0021] [Use of the Granules of the Present Invention] The granules of the present invention can be provided as they are or after being tableted as a supplement containing a soybean extract.

[0022] [Method for Producing Granules] The method for producing granules according to the present invention can utilize conventional granulation methods used in the technical fields of pharmaceuticals, quasi-drugs, cosmetics, food products, veterinary drugs, animal feed, and toiletries. Furthermore, the method for producing the granules of the present invention will be described below with specific examples.

[0023] The present invention provides a method for producing granules containing soybean extract, an emulsifier, dextrin, and cyclodextrin, comprising the following steps. Step (i): A step of preparing a powder composition containing soybean extract and cyclodextrin. Step (ii): A step to prepare a granulated solution containing an emulsifier and dextrin. Step (iii): A step of adding a granulation liquid to the powder composition and granulating it.

[0024] Step (i) is a step of preparing a powder composition containing soybean extract, for example, a step of mixing soybean extract with other components such as cyclodextrin to obtain a powder composition. The means of mixing the soybean extract and other components are not particularly limited and are ordinary mixing means used in the art. Examples of mixers used in these mixing means include tumbler mixers, V-type mixers, double-cone mixers, agitator mixers, high-speed fluidized bed mixers, drum mixers, fluidized bed mixers, and infinite mixers.

[0025] It is preferable to sift the soybean extract and other components before mixing. Sifting allows for the acquisition of a powder composition with excellent uniformity. The sieve mesh size can be set as appropriate, for example, to about 10 to 30 mesh.

[0026] Step (ii) is the step of preparing a granulated solution containing an emulsifier and dextrin. The solvent is not particularly limited as long as it is a common solvent used in the art. Examples of solvents include water, ethanol, hexane, ethyl acetate, and isopropyl alcohol. From the viewpoint of versatility, preferred solutions are water, anhydrous ethanol, or aqueous ethanol.

[0027] Step (iii) is the step of adding a granulation liquid to the powder composition to granulate it. Examples of granulation methods include agitation granulation, extrusion granulation, fluidized bed granulation, and tumbling granulation. Examples of granulators used in these granulation methods include fluidized bed granulators, tumbling fluidized bed granulators, Worster-type granulators, tumbling-type granulators, and agitation granulators.

[0028] Step (iii) is carried out, for example, by the following steps: Step (a): A step of adding a granulation liquid to the powder composition and kneading it. Step (b): A step of drying the kneaded powder composition.

[0029] Step (a) is a process of adding a granulation liquid to the powder composition and kneading it, and is used in stirring granulation, extrusion granulation, rolling granulation, etc. The amount of granulation liquid added to the powder composition can be appropriately set according to the state of the powder composition, such as the fluidity and particle size of the powder composition. It is preferable to use stirring granulation in step (a). Stirring granulation shortens the kneading time and can improve manufacturing efficiency.

[0030] Step (b) is a step of drying the kneaded powder composition. The method of drying the kneaded powder composition is not particularly limited as long as it is a common method used in the art. Examples of drying methods include fluidized bed drying, shelf drying, vacuum drying, vibration drying, microwave drying, and freeze-drying. Examples of drying equipment used in these drying methods include fluidized bed dryers, heated vacuum dryers, and freeze-dryers. Step (b) preferably uses the fluidized bed drying method. The fluidized bed drying method has a short drying time and can improve manufacturing efficiency. In addition, since the temperature of the powder composition is suppressed, changes in the state of the components contained in the powder composition can be suppressed.

[0031] Alternatively, step (iii) may be carried out by fluidized bed granulation. In the fluidized bed granulation method, the following steps are taken. Step (c): A step of spraying a granulation solution onto a powder composition in a fluid state.

[0032] Step (c) is a step of spraying a granulation solution onto a fluidized powder composition, and simultaneously drying the granulation solution. The supply temperature of the fluidized air is not particularly limited, but for example, it is 40 to 80°C. According to the fluidized bed granulation method, the powder composition can be granulated using a single apparatus. [Examples]

[0033] [Granule manufacturing] In the production of the granules in Examples 1-4 of Table 1 and the granules in Comparative Examples 1-7 of Table 2, the raw materials with the formulations shown in the granulation section of Tables 1 and 2 were prepared and sieved using a sieve of an appropriate size. The soybean extract in the granulation section was obtained by partially hydrolyzing soybean ethanol extract with hydrochloric acid, and contained 30% or more total isoflavone aglycones. Subsequently, the powder composition was mixed for 2 minutes in a stirring granulator (high-speed mixer LFS-GS-2J type, manufactured by Earth Technica Co., Ltd.). Then, the granulation liquid, with the composition shown in Tables 1 and 2, was added dropwise at an appropriate speed and kneaded for 3 minutes. The sucrose fatty acid ester in the granulation liquid was Ryoto Sugar Ester S-1670 manufactured by Mitsubishi Chemical Corporation. The dextrin added to the granulation section or granulation liquid was TK-16 manufactured by Matsutani Chemical Industry Co., Ltd., and the cyclodextrin was Kabamax W8 Hood manufactured by Wacker Chemical Corporation. Next, the kneaded powder composition was put into a fluid bed granulator (MP-01, manufactured by Powrec Co., Ltd.) and dried to produce granules. Drying was performed with an air supply temperature of 90°C, and the drying was stopped when the exhaust temperature reached 45°C or higher. After cooling, granules were obtained.

[0034] For Examples 1-4 in Table 1 and Comparative Examples 1-7 in Table 2, the adhesion within the agitated granulator and the adhesion within the fluidized bed granulator were evaluated according to the following criteria. 《Adhesion inside the stirring granulator》 ○: No adhesion inside the granulator. Continuous granulation is possible. ×: Granulation is not possible because the agitator (agitator blades) has been forcibly stopped. ××: The granulated material clumps together, making granulation impossible. 《Adhesion within a fluidized bed granulator》 ○: No adhesion of granulated powder within the fluidized bed granulator, yield of 80% or more. ×: Granulated powder adheres to the inside of the fluidized bed granulator, resulting in a yield of less than 80%.

[0035] [Table 1]

[0036] [Table 2]

[0037] As shown in Examples 1-4 of Table 1, by incorporating soybean extract, emulsifier, dextrin, and cyclodextrin, granules could be efficiently produced without adhesion in the granulator or adhesion in the fluidized bed dryer. On the other hand, as shown in Comparative Examples 1-7 of Table 2, when any of the soybean extract, emulsifier, dextrin, or cyclodextrin was omitted, adhesion in the granulator caused the agitator (stirring blade) to be forcibly stopped, preventing granulation, or the granulated material became clumpy and could not be granulated.

Claims

1. Granules containing soybean extract, emulsifier, dextrin, and cyclodextrin.

2. The granules according to claim 1, which contain 0.1% by mass or more and 1% by mass or less of an emulsifier relative to the granules.

3. The granules according to claim 1 or 2, wherein the HLB of the emulsifier is 7 or more and 18 or less.

4. A tablet comprising the granules described in claim 1 or 2.

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