Tablets containing soy extract

Abstract

The objective is to provide a tablet containing soybean extract that has sufficient disintegration properties while simultaneously possessing a desired tablet hardness. [Solution] A tablet containing soybean extract, agar, carrageenan, and sodium carboxymethylcellulose.

Description

Technical Field

[0001] The present invention relates to tablets containing a soybean extract.

Background Art

[0002] For pharmaceuticals and supplements, various active ingredients are formulated to exhibit their medicinal effects. However, depending on the nature, type, and amount of the active ingredient formulated, the disintegration time may become long. When the disintegration time becomes long, there is a problem that the active ingredient is not sufficiently absorbed in the body.

[0003] Regarding pharmaceuticals, in the disintegration test of the Japanese Pharmacopoeia, solid-form pharmaceuticals are required to disintegrate within 30 minutes. On the other hand, regarding supplements, there is no regulation that the disintegration time is within 30 minutes at the present stage. However, similar to pharmaceuticals, a design that disintegrates within 30 minutes is required, and in recent years, the disintegration property of supplements has also been attracting attention.

[0004] Therefore, as a method for improving the disintegration property of tablets, it is conceivable to add a large amount of a disintegrant. However, adding a large amount of a disintegrant causes problems such as a decrease in the hardness of the tablets and breakage during filling or distribution. At the same time, a problem that the fluidity of the tablet powder deteriorates may also occur. In addition, as a method for improving the disintegration property of tablets, a method of obtaining tablets by reducing the tableting pressure is conceivable. However, in this case, the tablets do not have sufficient hardness to withstand distribution as a product, and therefore the quality of the tablets cannot be guaranteed.

[0005] Tablets containing a soybean raw material, a polysaccharide, and cellulose, and further containing one or more components selected from cyclodextrin, tricalcium phosphate, and calcium citrate and having a disintegration time of less than 50 minutes are known (Patent Document 1).

[0006] Tablets containing plant extracts and carrageenan with improved disintegration properties are known (Patent Document 2). A technique is known to improve the disintegration properties of tablets containing active ingredients that have low disintegration properties when formed into tablets by including sodium carboxymethylcellulose and agar (Patent Document 3). A technique is known to improve the disintegration properties of tablets containing active ingredients that have low disintegration properties when formed into tablets by including carboxymethylcellulose and carrageenan (Patent Document 4). [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Japanese Patent Publication No. 2024-046637 [Patent Document 2] Japanese Patent Publication No. 2023-066089 [Patent Document 3] Japanese Patent Publication No. 2023-111768 [Patent Document 4] Japanese Patent Publication No. 2023-114946 [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] However, even with the method described in the above-mentioned patent document, when soy extract is incorporated, it is not possible to achieve both the disintegration properties and the desired hardness of tablets, which are currently in demand.

[0009] Therefore, the object of the present invention is to provide a tablet containing soybean extract that has sufficient disintegration properties while simultaneously having a desired tablet hardness. [Means for solving the problem]

[0010] The main components of this invention are as follows: 1. Tablets containing soybean extract, agar, carrageenan, and sodium carboxymethylcellulose. 2. The tablet according to 1, characterized in that it contains 0.8% by mass or more and 9.9% by mass or less of agar, 2.0% by mass or more and 9.6% by mass or less of carrageenan, and 0.5% by mass or more and 1.9% by mass or less of sodium carboxymethylcellulose. 3. The tablet according to 1, characterized in that it contains 6.0% by mass or more and 9.0% by mass or less of agar, 2.0% by mass or more and 4.8% by mass or less of carrageenan, and 1.5% by mass or more and 1.9% by mass or less of sodium carboxymethylcellulose. 4. A tablet according to any one of 1 to 3, characterized in that it contains 10% by mass or more and 50% by mass or less of soybean extract. 5. A tablet according to any one of 1 to 4, characterized in that it has a hardness of 100N or more and a disintegration time of 35 minutes or less. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a tablet containing soybean extract that has sufficient disintegration properties while simultaneously having a desired tablet hardness. [Modes for carrying out the invention]

[0012] The tablets of the present invention contain soybean extract, agar, carrageenan, and sodium carboxymethylcellulose.

[0013] 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.

[0014] 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.

[0015] 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.

[0016] 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.

[0017] 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. In addition, the fermented soybean extract is obtained by first extracting soybeans through an extraction process, which is a known method. In this process, for example, water or ethanol is used as the extraction solvent. Then, the soybean extract is fermented with microorganisms belonging to the genus Aspergillus such as Aspergillus oryzae; microorganisms belonging to the genus Bacillus such as Bacillus subtilis natto; microorganisms belonging to the genus Lactococcus such as Lactococcus garvieae; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedins and Streptococcus constellatus; microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus to obtain a fermented product of the soybean extract.

[0018] The fermented soybean germ extract is an extract obtained by fermenting soybean germ with microorganisms belonging to the genus Aspergillus such as Aspergillus oryzae; microorganisms belonging to the genus Lactococcus such as Lactococcus garvieae; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedins and Streptococcus constellatus; microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus, and then obtaining it through an extraction process, which is a known method. Examples of the extraction solvent include water, ethanol, etc. The fermented soybean germ extract contains equol, daizaines, genisteines, glyciteines, etc. In addition, the fermented soybean germ extract can be obtained by first extracting soybean germ through an extraction process, which is a known method. In this process, for example, water or ethanol is used as the extraction solvent. Then, the soybean germ extract is fermented with microorganisms belonging to the genus Aspergillus such as Aspergillus oryzae; microorganisms belonging to the genus Lactococcus such as Lactococcus garvieae; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedins and Streptococcus constellatus; microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus to obtain a fermented product of the soybean germ extract.

[0019] The fermented soybean hypocotyl extract is an extract obtained by fermenting soybean hypocotyls with microorganisms belonging to the genus Aspergillus such as Aspergillus oryzae; microorganisms belonging to the genus Lactococcus such as Lactococcus garvieae; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedicus and Streptococcus constellatus; microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus, and then subjecting the fermented soybean hypocotyls to an extraction process which is a known method. Examples of the extraction solvent include water, ethanol, and the like. The fermented soybean hypocotyl extract contains equol, daizeins, genisteins, glyciteins, and the like. Alternatively, the fermented soybean hypocotyl extract may be a fermented product of a soybean hypocotyl extract obtained by first extracting soybean hypocotyls by an extraction process which is a known method, using, for example, water or ethanol as the extraction solvent, and then fermenting the soybean hypocotyl extract with microorganisms belonging to the genus Aspergillus such as Aspergillus oryzae; microorganisms belonging to the genus Lactococcus such as Lactococcus garvieae; microorganisms belonging to the genus Streptococcus such as Streptococcus intermedicus and Streptococcus constellatus; microorganisms belonging to the genus Bacteroides such as Bacteroides ovatus.

[0020] Soybean isoflavones are isoflavones contained in soybeans and are also called phytoestrogens, and are known to have various physiological effects such as female hormone-like effects, antioxidant effects, anti-hemolytic effects, anti-cholesterol effects, anti-lipidemic effects, antibacterial effects, and the like. As soybean isoflavones, three types of aglycones (isoflavone aglycons), namely genistein, daidzein, and glycitein, and three types of glycosides (genistin, daidzin, 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.

[0021] Soybean isoflavone aglycones mean three types of aglycones, namely genistein, daidzein, and glycitein, which are non-glycosides among the isoflavones contained in soybeans.

[0022] The preferred amount of soybean extract in the tablet is 10% by mass or more and 50% by mass or less, preferably 20% by mass or more and 40% by mass or less, and particularly preferably 25% by mass or more and 35% by mass or less.

[0023] Agar is a high-molecular-weight polysaccharide extracted from red algae, possessing a linear structure based on repeating D-galactose and anhydro-L-galactose molecules. It is composed of agarose (neutral polysaccharide) and agaropectin (acidic polysaccharide). The agar that can be used in this invention is not particularly limited. Examples include purified agar for disintegration and Ina agar. These can be manufactured by known methods, or commercially available agars can be used.

[0024] Carrageenan is a polysaccharide that is naturally extracted mainly from red algae. Carrageenan is a galactan with a linear structure consisting of alternating α(1→3) and β(1→4) bonds, and the β(1→4)-linked galactose units exist partially or entirely as 3,6-anhydro-D-galactose and its sulfate ester. Carrageenan is classified into three types, kappa, iota, and lambda, depending on the amount of sulfate and anhydro groups contained in the molecule, but any of these types or mixtures thereof can be used.

[0025] Sodium carboxymethylcellulose is a compound in which the hydroxyl groups in cellulose are esterified, and crosslinked polymers of these compounds and their salts are commonly used as disintegrants. Sodium carboxymethylcellulose is a sodium salt in which the hydrogen atoms of carboxymethylcellulose are replaced with the monovalent metal sodium, and it is widely used in foods, pharmaceuticals, and other applications as a disintegrant and for other purposes. Due to its water solubility and moderate disintegration properties, sodium carboxymethylcellulose can more effectively exhibit the effects of the present invention compared to croscarmellose, which has intramolecular crosslinking, or calcium carboxymethylcellulose, which has a chelate structure with divalent metal salts. The sodium carboxymethylcellulose that can be used in the present invention is not particularly limited and can be produced by known methods or commercially available products can be used.

[0026] The hardness of the tablets of the present invention is preferably 100 N or higher at a pressure of 600 kgf. A hardness of 100 N or higher prevents the tablets from being damaged during distribution, filling, or when removing them from PTP (Press Through Pack) packaging.

[0027] The disintegration time of the tablets of the present invention is preferably within 35 minutes, and more preferably within 30 minutes, under a pressure of 600 kgf. The standard of within 30 minutes is based on the provision in the Japanese Pharmacopoeia concerning pharmaceuticals, which stipulates that the disintegration time of uncoated tablets should be within 30 minutes. If the disintegration time exceeds 30 minutes, the expected effect may not be obtained, for example, if the active ingredient is not sufficiently absorbed in the gastrointestinal tract, the required blood concentration cannot be obtained, or if the bioavailability decreases. The disintegration time should be measured according to the "Disintegration Test Method" described in the Japanese Pharmacopoeia.

[0028] It is preferable that the agar content is between 0.8% and 9.9% by mass, the carrageenan content is between 2.0% and 9.6% by mass, and the sodium carboxymethylcellulose content is between 0.5% and 1.9% by mass. By including these concentrations, tablets with a hardness of 100 N or more and a disintegration time of 35 minutes or less can be obtained at a pressure of 600 kgf.

[0029] It is particularly preferable that the agar content be between 6.0% and 9.0% by mass, the carrageenan content be between 2.0% and 4.8% by mass, and the sodium carboxymethylcellulose content be between 1.5% and 1.9% by mass. By including these concentrations, tablets with a hardness of 100 N or more and a disintegration time of 30 minutes or less can be obtained at a pressure of 600 kgf.

[0030] The tablets of the present invention may contain, as necessary, additives such as excipients, binders, lubricants, stabilizers, preservatives, fluidizers, thickeners, and colorants. In addition, other disintegrants other than agar, carrageenan, and sodium carboxymethylcellulose may be included, to the extent that the effects of the present invention are achieved.

[0031] Excipients are not particularly limited and include, for example, microcrystalline cellulose, lactose, sucrose, mannitol, glucose, starch, calcium phosphate, and calcium sulfate. These excipients may be formulated individually or in combination of two or more. The volume of the useful substance can be adjusted by adding excipients.

[0032] The binder is not particularly limited and examples include hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, macrogol, paraffin, acacia gum, gelatin, starch, starch hydrolysates, and pullulan. These binders may be formulated individually or in combination of two or more. By adding a binder, the powder components are given binding strength while simultaneously increasing fluidity, making it possible to produce stable tablets.

[0033] The lubricants are not particularly limited and include, for example, talc, colloidal silica, magnesium stearate, calcium stearate, magnesium carbonate, sodium benzoate, palmitic acid, sodium stearyl fumarate, waxes, hydrogenated vegetable oils, fats, and polyethylene glycol. These lubricants may be used individually or in combination of two or more. Adding lubricants can suppress the occurrence of tableting problems such as sticking during tablet manufacturing.

[0034] Other disintegrants are not particularly limited as long as they achieve the effects of the present invention, and examples include corn starch, partially pregelatinized starch, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, croscarmellose sodium, carboxymethyl starch sodium, crospolyvinylpyrrolidone, and alginates. These disintegrants may be formulated individually or in combination of two or more.

[0035] [Method of manufacturing tablets] The method for producing the tablets of the present invention is not particularly limited and can be produced using known additives used in food or pharmaceuticals, and conventional formulation methods employed in the food or pharmaceutical fields can be applied.

[0036] For example, methods include compressing a mixed powder containing various raw materials such as active ingredients, excipients, binders, and lubricants into tablets, or granulating the various raw materials using a stirring and mixing granulation method or a fluidized bed granulation method, then adding and mixing a lubricant, and finally compressing the mixture into tablets. The timing of adding the tablet components is not limited to these methods.

[0037] The equipment used for tableting can be any general tableting device, such as a rotary tablet press used in tablet manufacturing. For tablets with a diameter of 6-10 mm, the compression pressure is preferably 500-2000 kgf. [Examples]

[0038] [Tablet manufacturing] In the production of the tablets for Examples 1-9 in Table 1 and Comparative Examples 1-11 in Table 2, the soybean extract and cyclodextrin shown in the granulation section of Tables 1 and 2 were mixed for 2 minutes in a stirring granulator (high-speed mixer LFS-GS-2J type, manufactured by Earth Technica Co., Ltd.). The soybean extract was obtained by partially hydrolyzing soybean ethanol extract with hydrochloric acid and contained 30% or more total isoflavone aglycones. Subsequently, the sucrose fatty acid ester and dextrin shown in the granulation section of Tables 1 and 2 were added dropwise as an aqueous solution at an appropriate speed and kneaded for 3 minutes. 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. The granules obtained from the granulation process shown in Tables 1 and 2 were mixed with functional agents and excipients to produce a tableting powder. The prepared tableting powder was compressed using a single-shot tablet press N-30E (manufactured by Okada Seikou Co., Ltd.) with a punch shape of φ8.5 mm and R7, at a compression pressure of 600 kgf, to obtain tablets with a diameter of approximately 8.5 mm and a particle mass of 280 mg.

[0039] [Measuring tablet hardness] The hardness of the tablets produced during the manufacturing process described above was measured using a digital hardness tester KHT-40N (manufactured by Fujiwara Seisakusho). The average value of five sample tablets was measured, and this average value was used as the tablet hardness. The tablet hardness was evaluated according to the following evaluation criteria.

[0040] (Evaluation criteria for tablet hardness) ○: Tablet hardness of 100N or higher ×: Tablet hardness less than 100N

[0041] [Tablet disintegration test] The disintegration time of the manufactured tablets was measured according to "6.09 Disintegration Test Method" described in the general test methods of the "17th Edition of the Japanese Pharmacopoeia". Ion-exchanged water was used as the test solution. The disintegration tester used was a disintegration tester (NT-600 (product name), manufactured by Toyama Sangyo Co., Ltd.) manufactured by Toyama Sangyo Co., Ltd.

[0042] The test was conducted using 900 mL of test solution (purified water). The disintegration time of 6 tablets in water at 37°C was measured, and the average value was defined as the disintegration time. The disintegration properties were evaluated according to the following evaluation criteria.

[0043] (Criteria for evaluating disintegration) ◎: Collapse time is 30 minutes or less ○: Collapse time is 35 minutes or less ×: Collapse time exceeds 35 minutes

[0044] [Table 1]

[0045] [Table 2]

[0046] As shown in Examples 1 to 9, when the agar content was 0.8% to 9.9% by mass, the carrageenan content was 2.0% to 9.6% by mass, and the sodium carboxymethylcellulose content was 0.5% to 1.9% by mass, tablets with a hardness of 100N or more and a disintegration time of 35 minutes or less could be produced. As shown in Examples 1 and 8, when the agar content was 6.0% to 9.0% by mass, the carrageenan content was 2.0% to 4.8% by mass, and the sodium carboxymethylcellulose content was 1.5% to 1.9% by mass, tablets with a hardness of 100N or more and a disintegration time of 30 minutes or less could be produced.

Claims

1. A tablet containing soybean extract, agar, carrageenan, and sodium carboxymethylcellulose.

2. The tablet according to claim 1, characterized in that the agar content is 0.8% by mass or more and 9.9% by mass or less, the carrageenan content is 2.0% by mass or more and 9.6% by mass or less, and the carboxymethylcellulose sodium content is 0.5% by mass or more and 1.9% by mass or less.

3. The tablet according to claim 1, characterized in that the agar content is 6.0% by mass or more and 9.0% by mass or less, the carrageenan content is 2.0% by mass or more and 4.8% by mass or less, and the carboxymethylcellulose sodium content is 1.5% by mass or more and 1.9% by mass or less.

4. A tablet according to any one of claims 1 to 3, characterized in that it contains 10% by mass or more and 50% by mass or less of soybean extract.

5. A tablet according to any one of claims 1 to 3, characterized in that it has a hardness of 100 N or more and a disintegration time of 35 minutes or less.

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