WO2015190455A1 - Tablet containing sake yeast - Google Patents

Tablet containing sake yeast Download PDF

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Publication number
WO2015190455A1
WO2015190455A1 PCT/JP2015/066558 JP2015066558W WO2015190455A1 WO 2015190455 A1 WO2015190455 A1 WO 2015190455A1 JP 2015066558 W JP2015066558 W JP 2015066558W WO 2015190455 A1 WO2015190455 A1 WO 2015190455A1
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WIPO (PCT)
Prior art keywords
tablet
sake yeast
yeast
mass
silicon dioxide
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PCT/JP2015/066558
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French (fr)
Japanese (ja)
Inventor
友樹 永盛
大輔 金島
智夫 五木田
あゆみ 松野
秀明 南埜
菅藤　寿裕
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ライオン株式会社
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Application filed by ライオン株式会社 filed Critical ライオン株式会社
Priority to CN201580028973.9A priority Critical patent/CN106413728A/en
Priority to JP2016527804A priority patent/JPWO2015190455A1/en
Priority to KR1020167024717A priority patent/KR20170015277A/en
Publication of WO2015190455A1 publication Critical patent/WO2015190455A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • A61K36/064—Saccharomycetales, e.g. baker's yeast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds

Definitions

  • the present invention relates to a tablet containing sake yeast.
  • Sake yeast is rich in nutrients such as vitamins, amino acids, dietary fiber, and minerals. Therefore, the effects of nutritional supplementation and disease prevention can be expected by ingesting sake yeast.
  • Tablets containing sake yeast can be easily taken compared to sake yeast itself. Therefore, a tablet containing sake yeast is useful as a means for obtaining nutrition and effect exhibited by sake yeast.
  • sake yeast in order to obtain the above-described nutritional supplement and other effects, it is necessary to ingest a relatively large amount of sake yeast. Therefore, if there is little content of sake yeast in a tablet, the number of tablets to take will increase, and a problem will arise in ingestion. Therefore, in order to improve the dose of tablets containing sake yeast, it is required to increase the yeast concentration in the tablets.
  • Patent Document 1 after mixing a drug and a flow modifier such as light anhydrous silicic acid, the mixing powder and other additives are mixed to increase the mixing speed of the drug and the additive. It is described that the content uniformity can be increased.
  • Patent Document 2 describes that a binder such as light anhydrous silicic acid may be used in a method for producing a carnitine chloride-containing preparation in which carnitine chloride and dry yeast are mixed.
  • JP 2003-81876 A Japanese Patent Laid-Open No. 10-45580
  • Patent Document 1 relates to a preparation technique of a compound as a drug and is not assumed to be applied to yeast at all.
  • the technique described in Patent Document 2 is a technique for alleviating the deliquescence of carnitine chloride, and no study has been made on the tablet physical properties of the yeast preparation.
  • An object of the present invention is to obtain a tablet having sufficient tablet physical properties such as hardness and disintegration regardless of the content of sake yeast.
  • the present invention provides [1] to [3].
  • [1] Contains sake yeast and silicon dioxide, contains 15% by mass or more of sake yeast (A) per tablet, and contains silicon dioxide (B) relative to the content of sake yeast (A) The tablet whose mass ratio (B / A) of quantity is 0.7 / 100 or more and 38/100 or less.
  • the tablet according to [1] which is produced by mixing sake yeast and silicon dioxide (B) in advance and then adding and mixing other materials.
  • the method for producing a tablet according to [1] or [2] which comprises mixing sake yeast and silicon dioxide (B) in advance and then adding and mixing other materials.
  • a tablet having good tablet physical properties such as hardness and disintegration can be provided.
  • the tablet of the present invention contains sake yeast.
  • Sake yeast is yeast used for sake brewing. Yeasts used for sake brewing are mainly classified into S. cerevisiae. As sake yeast, association 6 yeast (K-6), association 7 yeast (K-7), association 9 yeast (K-9), association 601 yeast (K-601), association 701 yeast ( K-701), Association No. 901 yeast (K-901), Association No. 1001 yeast (K-1001), Association No. 1501 yeast (K-1501) (all of which are distributed by the Japan Brewing Association). Sake yeast may be either live cells or dead cells.
  • Sake yeast usually contains dry cells.
  • a dry microbial cell is a result obtained by drying a part of microbial cells, such as a microbial cell and / or a fragment of a microbial cell. Examples of the drying process include freeze drying, reduced pressure drying, aeration drying, and spray drying. Dry cells are usually in powder form.
  • the content of the sake yeast cell (A) (dry mass) in the tablet of the present invention is usually 15% by mass or more, preferably 20% by mass or more, as the content per tablet of the sake yeast cell. Yes, more preferably 23% by mass or more. Thereby, since the number of ingested tablets can be suppressed to an appropriate range, the dosing property can be improved.
  • the upper limit is preferably 70% by mass or less, more preferably 60% by mass or less, and still more preferably 50% by mass or less. Thereby, the hardness as a tablet can be maintained.
  • the content of sake yeast (A) per tablet is preferably 15% by mass to 70% by mass, more preferably 20% by mass to 60% by mass, and 23% by mass to 50% by mass. % Is more preferable.
  • Sake yeast cells (A) in the tablet of the present invention are contained in sake yeast.
  • the sake yeast and the sake yeast (A) may be the same.
  • components other than sake yeast (A) may be contained in sake yeast.
  • Examples of components other than the sake yeast (A) include fermentation broth and culture supernatant.
  • the tablet of the present invention contains silicon dioxide (also known as silicic anhydride, fine silicon dioxide, SiO 2 ) (B).
  • the content of silicon dioxide (B) is not particularly limited. However, the content of silicon dioxide (B) per tablet is usually 0.1% by mass or more, and preferably 0.3% by mass or more. The upper limit is preferably 24% by mass or less, and more preferably 12% by mass or less. The content of silicon dioxide (B) is preferably 0.1% by mass to 24% by mass, and more preferably 0.3% by mass to 12% by mass.
  • silicon dioxide (B) When the content of silicon dioxide (B) is at least the preferred lower limit, tablet hardness increases and good moldability is easily obtained. By setting it to a preferable upper limit value or less, a tablet with better disintegration can be obtained.
  • the mass ratio (B / A) of the content of silicon dioxide (B) to the content of sake yeast (A) (dry mass) is preferably 0.7 / 100 or more.
  • the upper limit is preferably 38/100 or less, and more preferably 25/100 or less.
  • (B / A) is preferably 0.7 / 100 or more and 38/100 or less, and more preferably 1/100 or more and 25/100 or less.
  • the effect of the present invention may contain any component that can be used for manufacturing tablets of other pharmaceuticals, quasi drugs, foods, etc., in an amount that does not impair the effect of the present invention.
  • optional components include excipients, binders, disintegrants, enteric polymers, water-insoluble polymers, lubricants, surfactants, colorants, flavoring agents, adsorbents, antistatic agents, disintegration extenders, Examples include foaming agents.
  • excipients examples include starch, corn starch, granulated sugar, mannitol, crystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium carbonate, calcium carbonate, purified white sugar, glucose, hydrous glucose, and lactose.
  • the content of the excipient is not particularly limited, but is preferably 0.1 to 80% by mass in total, and more preferably 10 to 70% by mass.
  • binder examples include sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, pullulan, dextrin, pregelatinized starch and the like.
  • the content of the binder is not particularly limited, but is preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.
  • disintegrants examples include croscarmellose sodium, cross-linked insoluble polyvinylpyrrolidone, partially pregelatinized starch, crospovidone, carboxymethylcellulose calcium (also known as carmellose calcium, CMC-Ca), carboxymethyl starch sodium, corn starch, etc. Is mentioned.
  • the content of the disintegrant is not particularly limited, but is preferably 0.1 to 30% by mass in total, and more preferably 1 to 20% by mass.
  • enteric polymer examples include hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and carboxymethylethyl cellulose.
  • water-insoluble polymer examples include aminoalkyl methacrylate copolymers (for example, Eudragit E, Eudragit RS, etc.), methacrylic acid copolymers (for example, Eudragit L30-55, etc.), and the like.
  • the lubricant examples include polyethylene glycol, talc, stearic acid or a salt thereof (eg, calcium stearate), sucrose fatty acid ester, and the like.
  • the content of the lubricant is not particularly limited, but is preferably 0.001 to 5% by mass, and more preferably 0.01 to 3% by mass.
  • the sucrose fatty acid ester examples include sucrose laurate, sucrose myristic ester, sucrose palmitate, sucrose stearate, and the like.
  • sucrose laurate sucrose monolaurate, sucrose dilaurate, sucrose trilaurate, etc.
  • sucrose myristic acid ester sucrose monomyristate, sucrose dimyristate, sucrose trimyristate
  • sucrose palmitate examples include sucrose monopalmitate, sucrose dipalmitate, and sucrose tripalmitate.
  • sucrose stearate examples include sucrose monostearate, sucrose distearate, and sucrose tristearate. Is mentioned.
  • surfactant examples include anionic surfactants such as sodium alkyl sulfate, nonionic surfactants such as polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, and polyoxyethylene castor oil derivative. .
  • colorant examples include tar dyes, caramel, red pepper, titanium oxide, riboflavin, green tea extract, copper chlorophyllin sodium, edible yellow No. 5, edible red No. 2, edible blue No. 2, etc., and edible lake dyes. Etc.
  • corrigent examples include sweeteners (eg, artificial sweeteners such as sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin), flavors (eg, lemon, lemon lime, orange, l-menthol, peppermint oil, Peppermint Micron X-8277-T, dry coat matcha tea # 421, etc.), acidulants (eg, citric acid, tartaric acid, malic acid, etc.), green tea powder and the like.
  • sweeteners eg, artificial sweeteners such as sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin
  • flavors eg, lemon, lemon lime, orange, l-menthol, peppermint oil, Peppermint Micron X-8277-T, dry coat matcha tea # 421, etc.
  • acidulants eg, citric acid, tartaric acid, malic acid, etc.
  • adsorbent examples include special calcium silicate (florite).
  • antistatic agent and the disintegration extender examples include light anhydrous silicic acid (aerosil).
  • foaming agent examples include baking soda.
  • the tablet production method is not particularly limited, and can be produced by adding and mixing raw materials containing sake yeast, silicon dioxide, optional ingredients, and the like.
  • the raw materials may be added and mixed all at once, or a part of the mixture may be mixed first and then the rest may be added and mixed. These materials are preferably added and mixed later. Thereby, the hardness of a tablet can be raised.
  • the other materials mean all materials (components) constituting the tablet except sake yeast and silicon dioxide.
  • Coating agents include celluloses such as carmellose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, and ethylcellulose; synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone; polyhydric alcohols such as polyethylene glycol, propylene glycol, and glycerin; triacetin; Examples include synthetic esters such as triethyl acid and glycerin fatty acid ester, natural substances such as shellac and pullulan, or combinations thereof.
  • pigments such as a titanium oxide and an iron oxide, mannitol, cetanol, and sodium lauryl sulfate as needed.
  • a brightening agent such as carnauba wax may be added.
  • a tablet excellent in tablet physical properties such as hardness and disintegration can be provided.
  • the hardness of the tablet can be measured using a hardness meter (for example, TH-203CP manufactured by Toyama Sangyo Co., Ltd.).
  • production of problems, such as a crack of a tablet and a chip, can be suppressed as hardness is 5 kgf or more.
  • the workability during the treatment can be improved if the hardness is 6 kgf or more.
  • the disintegration property can be evaluated by measuring the disintegration time using the method described in the Japanese Pharmacopoeia General Test Method.
  • the disintegration time is preferably less than 60 minutes, more preferably less than 40 minutes, and the shorter the time, the higher the immediate effect.
  • Example 6 After mixing sake yeast (SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in the yeast powder) and fine silicon dioxide (Carplex FPS-500, manufactured by DSL Japan Co., Ltd.) Crystalline cellulose (Ceolus (registered trademark) UF-F711, manufactured by Asahi Kasei Chemicals Corporation) and carboxymethylcellulose calcium (ECG-FA, manufactured by Nichirin Chemical Industries, Ltd.) were added and mixed, and then calcium stearate ( Calcium stearate, manufactured by Taihei Chemical Industry Co., Ltd.) was added and mixed, and tableted by the direct compression method. For tableting, the same rotary tableting machine as in Example 1 (LIBRA2, manufactured by Kikusui Seisakusho Co., Ltd.) was used.
  • sake yeast SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in the yeast powder
  • fine silicon dioxide Carplex FPS-500, manufactured by DSL Japan Co.
  • Example 7 Table 3 except that low-substituted hydroxypropylcellulose (L-HPC LH-21, manufactured by Shin-Etsu Chemical Co., Ltd.) was used instead of crystalline cellulose, and mannitol (PEARLITOL50C, manufactured by ROQUETTE FRERES) was used instead of carboxymethylcellulose calcium.
  • L-HPC LH-21 low-substituted hydroxypropylcellulose
  • PEARLITOL50C manufactured by ROQUETTE FRERES
  • the hardness and disintegration time of each tablet obtained were measured.
  • the hardness was measured with a hardness meter (TH-203CP, manufactured by Toyama Sangyo Co., Ltd.) and judged according to the following criteria.
  • the disintegration time was measured by conducting a disintegration test according to the tablet disintegration test method listed in the 16th revised Japanese Pharmacopoeia and measuring the disintegration time (minutes).
  • the disintegration test solution used ion-exchanged water, and the water bath temperature was 37 ° C. An average value of 6 measurements was calculated and judged according to the following criteria.
  • Tables 1 to 4 show the blending ratios and results in each example.
  • the tablets of Examples 1 to 11 were good in both hardness and disintegration. Among them, the tablet of Example 6 in which sake yeast and silicon dioxide were premixed was extremely excellent in hardness. On the other hand, the hardness of the tablets of Comparative Examples 1 and 2 where (B / A) is less than 0.7 / 100 and the disintegration property of the tablet of Comparative Example 3 where (B / A) exceeds 38/100 It was inferior to. These results indicate that the tablet of the present invention has sufficient tablet properties regardless of the yeast concentration.

Abstract

The present invention provides a tablet that contains a sake yeast and silicon dioxide; that contains, per tablet, at least 15 mass% of sake yeast cells (A); and that has a mass ratio (B/A), of the silicon dioxide (B) content to the sake yeast cells (A) content, of at least 0.7/100 and at most 38/100. This tablet is preferably produced by premixing the sake yeast and the silicon dioxide, and then mixing other ingredients therewith.

Description

清酒酵母含有錠剤Sake yeast-containing tablets
　本発明は、清酒酵母を含有する錠剤に関する。 The present invention relates to a tablet containing sake yeast.
　清酒酵母は、ビタミン類、アミノ酸類、食物繊維、ミネラル分などの栄養成分を豊富に含んでいる。そのため、清酒酵母の摂取により、栄養補給、疾病予防などの効果が期待できる。 Sake yeast is rich in nutrients such as vitamins, amino acids, dietary fiber, and minerals. Therefore, the effects of nutritional supplementation and disease prevention can be expected by ingesting sake yeast.
　清酒酵母を含む錠剤は、清酒酵母自体と比較して手軽に服用することができる。従って清酒酵母を含む錠剤は、清酒酵母の発揮する栄養補給、効果を得るための手段として有用である。しかしながら、上記の栄養補給やその他の効果を得るためには、比較的多量の清酒酵母を摂取する必要がある。そのため錠剤中の清酒酵母の含有量が少ないと、摂取する錠剤数が多くなりすぎて、服用性に問題が出る。従って、清酒酵母を含有する錠剤の服用性を向上するためには、錠剤中の酵母濃度を高めることが求められている。 Tablets containing sake yeast can be easily taken compared to sake yeast itself. Therefore, a tablet containing sake yeast is useful as a means for obtaining nutrition and effect exhibited by sake yeast. However, in order to obtain the above-described nutritional supplement and other effects, it is necessary to ingest a relatively large amount of sake yeast. Therefore, if there is little content of sake yeast in a tablet, the number of tablets to take will increase, and a problem will arise in ingestion. Therefore, in order to improve the dose of tablets containing sake yeast, it is required to increase the yeast concentration in the tablets.
　特許文献１には、薬物と軽質無水ケイ酸等の流動改質剤を混合した後、該混合紛体とその他の添加剤とを混合することで、薬物と添加剤の混合速度を速め、薬物の含量均一性を高めることができることが記載されている。特許文献２には、塩化カルニチンと乾燥酵母を混合する塩化カルニチン含有製剤の製造方法において、軽質無水ケイ酸等の結合剤を用いてもよいことが記載されている。 In Patent Document 1, after mixing a drug and a flow modifier such as light anhydrous silicic acid, the mixing powder and other additives are mixed to increase the mixing speed of the drug and the additive. It is described that the content uniformity can be increased. Patent Document 2 describes that a binder such as light anhydrous silicic acid may be used in a method for producing a carnitine chloride-containing preparation in which carnitine chloride and dry yeast are mixed.
特開２００３－８１８７６号公報JP 2003-81876 A 特開平１０－４５５８０号公報Japanese Patent Laid-Open No. 10-45580
　しかし、特許文献１の技術は、薬物としての化合物の製剤技術に関するものであり、酵母に適用することは全く想定していない。また、特許文献２に記載の技術は、塩化カルニチンの潮解性を緩和する技術であり、酵母製剤の錠剤物性について何ら検討されていなかった。 However, the technique of Patent Document 1 relates to a preparation technique of a compound as a drug and is not assumed to be applied to yeast at all. Moreover, the technique described in Patent Document 2 is a technique for alleviating the deliquescence of carnitine chloride, and no study has been made on the tablet physical properties of the yeast preparation.
　本発明は、清酒酵母の含有量にかかわらず、硬度、崩壊性等の錠剤物性が十分な錠剤を得ることを目的とする。 An object of the present invention is to obtain a tablet having sufficient tablet physical properties such as hardness and disintegration regardless of the content of sake yeast.
　本発明は、〔１〕～〔３〕を提供する。
〔１〕清酒酵母と二酸化ケイ素とを含有し、清酒酵母菌体（Ａ）を錠剤１錠あたり１５質量％以上含有し、清酒酵母菌体（Ａ）の含有量に対する二酸化ケイ素（Ｂ）の含有量の質量比率（Ｂ／Ａ）が０．７／１００以上３８／１００以下である錠剤。
〔２〕清酒酵母と二酸化ケイ素（Ｂ）とをあらかじめ混合してから他の材料を添加混合して製造される、〔１〕に記載の錠剤。
〔３〕清酒酵母と二酸化ケイ素（Ｂ）とをあらかじめ混合してから他の材料を添加混合することを含む、〔１〕又は〔２〕に記載の錠剤の製造方法。 The present invention provides [1] to [3].
[1] Contains sake yeast and silicon dioxide, contains 15% by mass or more of sake yeast (A) per tablet, and contains silicon dioxide (B) relative to the content of sake yeast (A) The tablet whose mass ratio (B / A) of quantity is 0.7 / 100 or more and 38/100 or less.
[2] The tablet according to [1], which is produced by mixing sake yeast and silicon dioxide (B) in advance and then adding and mixing other materials.
[3] The method for producing a tablet according to [1] or [2], which comprises mixing sake yeast and silicon dioxide (B) in advance and then adding and mixing other materials.
　本発明によれば、硬度、崩壊性等の錠剤物性が良好な錠剤を提供することができる。 According to the present invention, a tablet having good tablet physical properties such as hardness and disintegration can be provided.
　本発明の錠剤は、清酒酵母を含有する。清酒酵母とは、清酒醸造に用いられる酵母である。清酒醸造に用いられる酵母は、主としてサッカロミセス・セレビシエ（Ｓ．ｃｅｒｅｖｉｓｉａｅ）に分類される。清酒酵母としては、協会６号酵母（Ｋ－６）、協会７号酵母（Ｋ－７）、協会９号酵母（Ｋ－９）、協会６０１号酵母（Ｋ－６０１）、協会７０１号酵母（Ｋ－７０１）、協会９０１号酵母（Ｋ－９０１）、協会１００１号酵母（Ｋ－１００１）、協会１５０１号酵母（Ｋ－１５０１）（いずれも公益財団法人日本醸造協会頒布）が例示される。清酒酵母は、生菌体及び死菌体のいずれでもよい。 The tablet of the present invention contains sake yeast. Sake yeast is yeast used for sake brewing. Yeasts used for sake brewing are mainly classified into S. cerevisiae. As sake yeast, association 6 yeast (K-6), association 7 yeast (K-7), association 9 yeast (K-9), association 601 yeast (K-601), association 701 yeast ( K-701), Association No. 901 yeast (K-901), Association No. 1001 yeast (K-1001), Association No. 1501 yeast (K-1501) (all of which are distributed by the Japan Brewing Association). Sake yeast may be either live cells or dead cells.
　清酒酵母は、通常は乾燥菌体を含む。乾燥菌体とは、菌体及び／又は菌体の破砕片など菌体の一部を乾燥処理して得られる結果物である。乾燥処理としては、凍結乾燥、減圧乾燥、通気乾燥、噴霧乾燥が例示される。乾燥菌体は、通常粉末状である。 Sake yeast usually contains dry cells. A dry microbial cell is a result obtained by drying a part of microbial cells, such as a microbial cell and / or a fragment of a microbial cell. Examples of the drying process include freeze drying, reduced pressure drying, aeration drying, and spray drying. Dry cells are usually in powder form.
　本発明の錠剤における清酒酵母菌体（Ａ）(乾燥質量)の含有量は、清酒酵母菌体の錠剤１錠あたりの含有量として、通常１５質量％以上であり、好ましくは２０質量％以上であり、より好ましくは２３質量％以上である。これにより、摂取錠数を適度な範囲に抑えることができるので、服用性を向上させることができる。上限は、７０質量％以下であることが好ましく、６０質量％以下であることがより好ましく、５０質量％以下であることが更に好ましい。これにより、錠剤としての硬度を保持することができる。清酒酵母菌体（Ａ）の錠剤１錠あたりの含有量は、１５質量％～７０質量％であることが好ましく、２０質量％～６０質量％であることがより好ましく、２３質量％～５０質量％であることが更に好ましい。 The content of the sake yeast cell (A) (dry mass) in the tablet of the present invention is usually 15% by mass or more, preferably 20% by mass or more, as the content per tablet of the sake yeast cell. Yes, more preferably 23% by mass or more. Thereby, since the number of ingested tablets can be suppressed to an appropriate range, the dosing property can be improved. The upper limit is preferably 70% by mass or less, more preferably 60% by mass or less, and still more preferably 50% by mass or less. Thereby, the hardness as a tablet can be maintained. The content of sake yeast (A) per tablet is preferably 15% by mass to 70% by mass, more preferably 20% by mass to 60% by mass, and 23% by mass to 50% by mass. % Is more preferable.
　本発明の錠剤における清酒酵母菌体（Ａ）は、清酒酵母中に含有される。清酒酵母と清酒酵母菌体（Ａ）は、同一である場合もある。また清酒酵母中に清酒酵母菌体（Ａ）以外の成分が含有されていてもよい。当該清酒酵母菌体（Ａ）以外の成分としては、例えば、発酵液、培養上清等が挙げられる。 Sake yeast cells (A) in the tablet of the present invention are contained in sake yeast. The sake yeast and the sake yeast (A) may be the same. In addition, components other than sake yeast (A) may be contained in sake yeast. Examples of components other than the sake yeast (A) include fermentation broth and culture supernatant.
　本発明の錠剤は、二酸化ケイ素（別名：無水ケイ酸、微粒二酸化ケイ素、ＳｉＯ2）（Ｂ）を含有する。二酸化ケイ素（Ｂ）の含有量は、特に限定されない。しかし、二酸化ケイ素（Ｂ）の錠剤１錠あたりの含有量は、通常０．１質量％以上であり、好ましくは０．３質量％以上である。上限は、２４質量％以下であることが好ましく、１２質量％以下であることがより好ましい。二酸化ケイ素（Ｂ）の含有量は、０．１質量％～２４質量％であることが好ましく、０．３質量％～１２質量％であることがより好ましい。 The tablet of the present invention contains silicon dioxide (also known as silicic anhydride, fine silicon dioxide, SiO 2 ) (B). The content of silicon dioxide (B) is not particularly limited. However, the content of silicon dioxide (B) per tablet is usually 0.1% by mass or more, and preferably 0.3% by mass or more. The upper limit is preferably 24% by mass or less, and more preferably 12% by mass or less. The content of silicon dioxide (B) is preferably 0.1% by mass to 24% by mass, and more preferably 0.3% by mass to 12% by mass.
　二酸化ケイ素（Ｂ）の含有量が好ましい下限値以上であることで、錠剤硬度が高くなり良好な成形性を得られやすくなる。好ましい上限値以下とすることで、崩壊性がより良好な錠剤を得ることができる。 When the content of silicon dioxide (B) is at least the preferred lower limit, tablet hardness increases and good moldability is easily obtained. By setting it to a preferable upper limit value or less, a tablet with better disintegration can be obtained.
　本発明の錠剤において、清酒酵母菌体（Ａ）（乾燥質量）の含有量に対する二酸化ケイ素（Ｂ）の含有量の質量比率（Ｂ／Ａ）が、０．７／１００以上であることが好ましく、１／１００以上であることがより好ましく、上限は、３８／１００以下であることが好ましく、２５／１００以下であることがより好ましい。これにより、錠剤物性をより向上させることができる。（Ｂ／Ａ）は、０．７／１００以上３８／１００以下であることが好ましく、１／１００以上２５／１００以下であることがより好ましい。 In the tablet of the present invention, the mass ratio (B / A) of the content of silicon dioxide (B) to the content of sake yeast (A) (dry mass) is preferably 0.7 / 100 or more. The upper limit is preferably 38/100 or less, and more preferably 25/100 or less. Thereby, a tablet physical property can be improved more. (B / A) is preferably 0.7 / 100 or more and 38/100 or less, and more preferably 1/100 or more and 25/100 or less.
　（Ｂ／Ａ）が好ましい下限値以上であることで、錠剤硬度が高くなり良好な成形性を得られやすくなる。好ましい上限値以下とすることで、崩壊性がより良好な錠剤を得ることができる。 When (B / A) is equal to or more than the preferred lower limit, tablet hardness increases and good moldability is easily obtained. By setting it to a preferable upper limit value or less, a tablet with better disintegration can be obtained.
　本発明の効果に悪影響を及ぼさない限り、本発明の効果を損なわない程度の量で、他の医薬品、医薬部外品、食品等の錠剤の製造に用い得る任意の成分を含んでいてもよい。任意成分としては、例えば、賦形剤、結合剤、崩壊剤、腸溶性ポリマー、水不溶性ポリマー、滑沢剤、界面活性剤、着色剤、矯味剤、吸着剤、帯電防止剤、崩壊延長剤、発泡剤などが挙げられる。 As long as the effect of the present invention is not adversely affected, it may contain any component that can be used for manufacturing tablets of other pharmaceuticals, quasi drugs, foods, etc., in an amount that does not impair the effect of the present invention. . Examples of optional components include excipients, binders, disintegrants, enteric polymers, water-insoluble polymers, lubricants, surfactants, colorants, flavoring agents, adsorbents, antistatic agents, disintegration extenders, Examples include foaming agents.
　賦形剤としては、例えば、デンプン、コーンスターチ、グラニュウ糖、マンニトール、結晶セルロース、低置換度ヒドロキシプロピルセルロース、炭酸マグネシウム、炭酸カルシウム、精製白糖、ブドウ糖、含水ブドウ糖、乳糖などが挙げられる。賦形剤の含有量は特に限定されないが、合計で０．１～８０質量％が好ましく、１０～７０質量％であることが更に好ましい。 Examples of excipients include starch, corn starch, granulated sugar, mannitol, crystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium carbonate, calcium carbonate, purified white sugar, glucose, hydrous glucose, and lactose. The content of the excipient is not particularly limited, but is preferably 0.1 to 80% by mass in total, and more preferably 10 to 70% by mass.
　結合剤としては、例えば、ショ糖、ゼラチン、アラビアゴム末、メチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、ポリビニルピロリドン、プルラン、デキストリン、α化デンプンなどが挙げられる。結合剤の含有量は特に限定されないが、０．１～１０質量％が好ましく、１～５質量％であることがより好ましい。 Examples of the binder include sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, pullulan, dextrin, pregelatinized starch and the like. The content of the binder is not particularly limited, but is preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.
　崩壊剤としては、例えば、クロスカルメロースナトリウム、クロスリンクドインソルブルポリビニルピロリドン、部分アルファ化デンプン、クロスポビドン、カルボキシメチルセルロースカルシウム（別名：カルメロースカルシウム、ＣＭＣ－Ｃａ）、カルボキシメチルスターチナトリウム、コーンスターチなどが挙げられる。崩壊剤の含有量は特に限定されないが、合計で０．１～３０質量％が好ましく、１～２０質量％であることがより好ましい。 Examples of disintegrants include croscarmellose sodium, cross-linked insoluble polyvinylpyrrolidone, partially pregelatinized starch, crospovidone, carboxymethylcellulose calcium (also known as carmellose calcium, CMC-Ca), carboxymethyl starch sodium, corn starch, etc. Is mentioned. The content of the disintegrant is not particularly limited, but is preferably 0.1 to 30% by mass in total, and more preferably 1 to 20% by mass.
　腸溶性ポリマーとしては、例えば、ヒドロキシプロピルメチルセルロースフタレート、セルロースアセテートフタレート、カルボキシメチルエチルセルロースなどが挙げられる。 Examples of the enteric polymer include hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, and carboxymethylethyl cellulose.
　水不溶性ポリマーとしては、例えば、アミノアルキルメタアクリレートコポリマー（例えば、オイドラギッドＥ、オイドラギッドＲＳ等）、メタクリル酸コポリマー（例えば、オイドラギットＬ３０－５５等）などが挙げられる。 Examples of the water-insoluble polymer include aminoalkyl methacrylate copolymers (for example, Eudragit E, Eudragit RS, etc.), methacrylic acid copolymers (for example, Eudragit L30-55, etc.), and the like.
　滑沢剤としては、例えば、ポリエチレングリコール、タルク、ステアリン酸又はその塩（例：ステアリン酸カルシウム）、ショ糖脂肪酸エステルなどが挙げられる。滑沢剤の含有量は特に限定されないが、０．００１～５質量％が好ましく、０．０１～３質量％であることが更に好ましい。該ショ糖脂肪酸エステルとしては、例えば、ショ糖ラウリン酸エステル、ショ糖ミリスチン酸エステル、ショ糖パルミチン酸エステル、ショ糖ステアリン酸エステルなどが挙げられる。ショ糖ラウリン酸エステルとしては、ショ糖モノラウレート、ショ糖ジラウレート、ショ糖トリラウレート等が、ショ糖ミリスチン酸エステルとしては、ショ糖モノミリステート、ショ糖ジミリステート、ショ糖トリミリステート等が、ショ糖パルミチン酸エステルとしては、ショ糖モノパルミテート、ショ糖ジパルミテート、ショ糖トリパルミテート等が、ショ糖ステアリン酸エステルとしては、ショ糖モノステアレート、ショ糖ジステアレート、ショ糖トリステアレート等が挙げられる。 Examples of the lubricant include polyethylene glycol, talc, stearic acid or a salt thereof (eg, calcium stearate), sucrose fatty acid ester, and the like. The content of the lubricant is not particularly limited, but is preferably 0.001 to 5% by mass, and more preferably 0.01 to 3% by mass. Examples of the sucrose fatty acid ester include sucrose laurate, sucrose myristic ester, sucrose palmitate, sucrose stearate, and the like. As sucrose laurate, sucrose monolaurate, sucrose dilaurate, sucrose trilaurate, etc., as sucrose myristic acid ester, sucrose monomyristate, sucrose dimyristate, sucrose trimyristate, Examples of sucrose palmitate include sucrose monopalmitate, sucrose dipalmitate, and sucrose tripalmitate. Examples of sucrose stearate include sucrose monostearate, sucrose distearate, and sucrose tristearate. Is mentioned.
　界面活性剤としては、例えば、アルキル硫酸ナトリウム等のアニオン系界面活性剤、ポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレン脂肪酸エステル及びポリオキシエチレンヒマシ油誘導体等の非イオン系界面活性剤などが挙げられる。 Examples of the surfactant include anionic surfactants such as sodium alkyl sulfate, nonionic surfactants such as polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, and polyoxyethylene castor oil derivative. .
　着色剤としては、例えば、タール色素、カラメル、ベンガラ、酸化チタン、リボフラビン類、緑茶抽出物、銅クロロフィリンナトリウム、食用黄色５号，食用赤色２号，食用青色２号などの食用色素、食用レーキ色素などが挙げられる。 Examples of the colorant include tar dyes, caramel, red pepper, titanium oxide, riboflavin, green tea extract, copper chlorophyllin sodium, edible yellow No. 5, edible red No. 2, edible blue No. 2, etc., and edible lake dyes. Etc.
　矯味剤としては、例えば、甘味剤（例、サッカリンナトリウム、グリチルリチン酸二カリウム、アスパルテーム、ステビア、ソーマチンなどの人工甘味料など）、香料（例、レモン、レモンライム、オレンジ、ｌ－メントール、ハッカ油、ペパーミントミクロンＸ－８２７７－Ｔ、ドライコート抹茶＃４２１など）、酸味料（例、クエン酸、酒石酸、リンゴ酸など）、緑茶末などが挙げられる。 Examples of the corrigent include sweeteners (eg, artificial sweeteners such as sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin), flavors (eg, lemon, lemon lime, orange, l-menthol, peppermint oil, Peppermint Micron X-8277-T, dry coat matcha tea # 421, etc.), acidulants (eg, citric acid, tartaric acid, malic acid, etc.), green tea powder and the like.
　吸着剤としては、例えば、特殊ケイ酸カルシウム（フローライト）などが挙げられる。 Examples of the adsorbent include special calcium silicate (florite).
　帯電防止剤、崩壊延長剤としては、例えば、軽質無水ケイ酸（エアロジル）などが挙げられる。 Examples of the antistatic agent and the disintegration extender include light anhydrous silicic acid (aerosil).
　発泡剤としては、例えば、重曹などが挙げられる。 Examples of the foaming agent include baking soda.
　錠剤の製造方法は特に限定されず、清酒酵母、二酸化ケイ素、任意の成分等を含む原料を添加混合して製造することができる。原料の添加混合は、一括添加して混合してもよいし一部を先に混合してから残りを添加し混合することでもよいが、清酒酵母と二酸化ケイ素をあらかじめ添加混合してから、その他の材料を後から添加混合することが好ましい。これにより、錠剤の硬度を高めることができる。他の材料とは、清酒酵母及び二酸化ケイ素を除く、錠剤を構成するすべての材料（成分）を意味する。 The tablet production method is not particularly limited, and can be produced by adding and mixing raw materials containing sake yeast, silicon dioxide, optional ingredients, and the like. The raw materials may be added and mixed all at once, or a part of the mixture may be mixed first and then the rest may be added and mixed. These materials are preferably added and mixed later. Thereby, the hardness of a tablet can be raised. The other materials mean all materials (components) constituting the tablet except sake yeast and silicon dioxide.
　製造には、必要に応じて湿式造粒、乾式造粒等の方法を用いて造粒することが可能であり、清酒酵母、二酸化ケイ素と上記添加物とを混合して打錠する直接打錠法でも、圧縮成形による乾式顆粒とした後、または水の混合溶媒を加えて練合、造粒、乾燥して湿式顆粒とした後、あるいは水等の溶媒に添加物を溶解させ噴霧乾燥して湿式顆粒とした後、圧縮錠剤を製する間接打錠法でもよく、またこれらを組合せた方法によることもできる。このうち直接打錠法が好ましい。 For production, it is possible to perform granulation using methods such as wet granulation and dry granulation as required, and direct tableting by mixing sake yeast, silicon dioxide and the above additives for tableting. In addition, after forming dry granules by compression molding, adding a mixed solvent of water, kneading, granulating and drying to form wet granules, or dissolving additives in a solvent such as water and spray drying After forming the wet granule, an indirect tableting method for producing a compressed tablet may be used, or a combination of these methods may be used. Of these, the direct tableting method is preferred.
　錠剤は、コーティング剤によるコーティング処理が施されていてもよい。コーティング剤としては、カルメロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、メチルセルロース、エチルセルロース等のセルロース類、ポリビニルアルコール、ポリビニルピロリドン等の合成高分子、ポリエチレングリコール、プロピレングリコール、グリセリン等の多価アルコール、トリアセチン、クエン酸トリエチル、グリセリン脂肪酸エステル等の合成エステル類、シェラック、プルラン等の天然物質、又はこれらの組み合わせが例示される。また、必要に応じて酸化チタン、酸化鉄などの顔料、マンニトール、セタノール、ラウリル硫酸ナトリウム等の任意成分を加えてもよい。また、フィルムコーティング後に、カルナバロウ等の光沢化剤を加えてもよい。 Tablets may be coated with a coating agent. Coating agents include celluloses such as carmellose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, and ethylcellulose; synthetic polymers such as polyvinyl alcohol and polyvinylpyrrolidone; polyhydric alcohols such as polyethylene glycol, propylene glycol, and glycerin; triacetin; Examples include synthetic esters such as triethyl acid and glycerin fatty acid ester, natural substances such as shellac and pullulan, or combinations thereof. Moreover, you may add arbitrary components, such as pigments, such as a titanium oxide and an iron oxide, mannitol, cetanol, and sodium lauryl sulfate as needed. Further, after film coating, a brightening agent such as carnauba wax may be added.
　本発明によれば、硬度、崩壊性等の錠剤物性に優れた錠剤を提供することができる。 According to the present invention, a tablet excellent in tablet physical properties such as hardness and disintegration can be provided.
　錠剤の硬度は、硬度計（例えば、富山産業株式会社、製ＴＨ－２０３ＣＰ）を用いて測定することができる。硬度が５ｋｇｆ以上であると、錠剤の割れ、欠け等の問題の発生を抑制することができる。錠剤にコーティング等の処理を施す場合には、硬度が６ｋｇｆ以上であると、該処理の際の作業性を向上することができる。 The hardness of the tablet can be measured using a hardness meter (for example, TH-203CP manufactured by Toyama Sangyo Co., Ltd.). Generation | occurrence | production of problems, such as a crack of a tablet and a chip, can be suppressed as hardness is 5 kgf or more. When the tablet is subjected to a treatment such as coating, the workability during the treatment can be improved if the hardness is 6 kgf or more.
　崩壊性は、日本薬局方一般試験法に記載される方法を用いて崩壊時間を測定し評価することができる。崩壊時間は、６０分未満であることが好ましく、４０分未満であることがより好ましく、短いほど即効性に優れた錠剤であると評価できる。 The disintegration property can be evaluated by measuring the disintegration time using the method described in the Japanese Pharmacopoeia General Test Method. The disintegration time is preferably less than 60 minutes, more preferably less than 40 minutes, and the shorter the time, the higher the immediate effect.
　以下に、実施例を参照して本発明をより詳細に説明するが、本発明の実施態様は、この実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the embodiments of the present invention are not limited to these examples.
［実施例１～５］
　清酒酵母（ＳＡＭｅ含有乾燥酵母、三菱ガス化学（株）製、酵母粉末中の菌体量７０％）、微粒二酸化ケイ素（カープレックスＦＰＳ－５００、ＤＳＬ．ジャパン（株）製）、結晶セルロース（セオラス（登録商標）ＵＦ－Ｆ７１１、旭化成ケミカルズ（株）製）、及びカルボキシメチルセルロースカルシウム（Ｅ．Ｃ．Ｇ－ＦＡ、ニチリン化学工業（株）製）を添加混合し、次いでステアリン酸カルシウム（ステアリン酸カルシウム、太平化学産業（株）製）を添加混合し、直打法により１２ｋＮで打錠した。打錠には、ロータリー式打錠機（ＬＩＢＲＡ２、菊水製作所（株）製）を用いた。 [Examples 1 to 5]
Sake yeast (SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in the yeast powder), fine silicon dioxide (Carplex FPS-500, manufactured by DSL Japan Co., Ltd.), crystalline cellulose (Theolas) (Registered Trademark) UF-F711, Asahi Kasei Chemicals Co., Ltd.) and carboxymethyl cellulose calcium (ECG-FA, manufactured by Nichirin Chemical Industry Co., Ltd.) are added and mixed, and then calcium stearate (calcium stearate, Taihei) Chemical Industry Co., Ltd.) was added and mixed, and tableted at 12 kN by the direct compression method. A rotary tableting machine (LIBRA2, manufactured by Kikusui Seisakusho Co., Ltd.) was used for tableting.
［実施例６］
　清酒酵母（ＳＡＭｅ含有乾燥酵母、三菱ガス化学（株）製、酵母粉末中の菌体量７０％）と微粒二酸化ケイ素（カープレックスＦＰＳ－５００、ＤＳＬ．ジャパン（株）製）を混合した後、結晶セルロース（セオラス（登録商標）ＵＦ－Ｆ７１１、旭化成ケミカルズ（株）製）、及びカルボキシメチルセルロースカルシウム（Ｅ．Ｃ．Ｇ―ＦＡ、ニチリン化学工業（株）製）を添加混合し、ついでステアリン酸カルシウム（ステアリン酸カルシウム、太平化学産業（株）製）を添加混合し、直打法により打錠した。打錠には、実施例１と同様のロータリー式打錠機（ＬＩＢＲＡ２、菊水製作所（株）製）を用いた。 [Example 6]
After mixing sake yeast (SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in the yeast powder) and fine silicon dioxide (Carplex FPS-500, manufactured by DSL Japan Co., Ltd.) Crystalline cellulose (Ceolus (registered trademark) UF-F711, manufactured by Asahi Kasei Chemicals Corporation) and carboxymethylcellulose calcium (ECG-FA, manufactured by Nichirin Chemical Industries, Ltd.) were added and mixed, and then calcium stearate ( Calcium stearate, manufactured by Taihei Chemical Industry Co., Ltd.) was added and mixed, and tableted by the direct compression method. For tableting, the same rotary tableting machine as in Example 1 (LIBRA2, manufactured by Kikusui Seisakusho Co., Ltd.) was used.
［実施例７］
　結晶セルロースの代わりに低置換度ヒドロキシプロピルセルロース（Ｌ－ＨＰＣ　ＬＨ－２１、信越化学工業（株）製）、カルボキシメチルセルロースカルシウムの代わりにマンニトール（ＰＥＡＲＬＩＴＯＬ５０Ｃ、ＲＯＱＵＥＴＴＥ　ＦＲＥＲＥＳ製）を使用した以外は、表３の組成にて実施例１と同様の添加方法で各成分を混合し、直打法により打錠した。打錠には、実施例１と同様のロータリー式打錠機（ＬＩＢＲＡ２、菊水製作所（株）製）を用いた。 [Example 7]
Table 3 except that low-substituted hydroxypropylcellulose (L-HPC LH-21, manufactured by Shin-Etsu Chemical Co., Ltd.) was used instead of crystalline cellulose, and mannitol (PEARLITOL50C, manufactured by ROQUETTE FRERES) was used instead of carboxymethylcellulose calcium. Each component was mixed by the same addition method as Example 1 by the composition of this, and tableted by the direct compression method. For tableting, the same rotary tableting machine as in Example 1 (LIBRA2, manufactured by Kikusui Seisakusho Co., Ltd.) was used.
［比較例１～３、実施例８～１１］
　清酒酵母（ＳＡＭｅ含有乾燥酵母、三菱ガス化学（株）製、酵母粉末中の菌体量７０％）と、二酸化ケイ素（カープレックスＦＰＳ－５００、ＤＳＬ．ジャパン製）、トウモロコシデンプン（日本コーンスターチ（株）製）を添加混合し、次いでステアリン酸カルシウム（ステアリン酸カルシウム、太平化学産業（株）製）を加えて、１分間混合した。得られた混合粉体をロータリー打錠機（ＬＩＢＲＡ２、（株）菊水製作所）にて直打法により１２ｋＮで打錠し、錠剤を作製した。 [Comparative Examples 1 to 3, Examples 8 to 11]
Sake yeast (SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in the yeast powder), silicon dioxide (Carplex FPS-500, manufactured by DSL Japan), corn starch (Nippon Corn Starch Co., Ltd.) )) Was added, and then calcium stearate (calcium stearate, manufactured by Taihei Chemical Sangyo Co., Ltd.) was added and mixed for 1 minute. The obtained mixed powder was tableted at 12 kN by a direct tableting method using a rotary tableting machine (LIBRA2, Kikusui Seisakusho) to prepare tablets.
　得られた各錠剤の硬度と崩壊時間を測定した。硬度の測定は、硬度計（ＴＨ－２０３ＣＰ、富山産業（株）製）によって行い、下記の基準により判定した。崩壊時間の測定は、第十六改正日本薬局方に収載される錠剤の崩壊試験法に準じて崩壊試験を行い、崩壊時間（分）を測定した。崩壊試験液はイオン交換水を使用し、水浴温度は３７℃とした。測定回数６回の平均値を算出し、下記の基準により判定した。 The hardness and disintegration time of each tablet obtained were measured. The hardness was measured with a hardness meter (TH-203CP, manufactured by Toyama Sangyo Co., Ltd.) and judged according to the following criteria. The disintegration time was measured by conducting a disintegration test according to the tablet disintegration test method listed in the 16th revised Japanese Pharmacopoeia and measuring the disintegration time (minutes). The disintegration test solution used ion-exchanged water, and the water bath temperature was 37 ° C. An average value of 6 measurements was calculated and judged according to the following criteria.
　［硬度の判定基準］
　　硬度が５ｋｇｆ以上であれば許容と判断した。
　　☆：８ｋｇｆ以上
　　◎：６ｋｇｆ以上８ｋｇｆ未満
　　○：５ｋｇｆ以上６ｋｇｆ未満
　　×：５ｋｇｆ未満 [Criteria for hardness]
If the hardness was 5 kgf or more, it was judged acceptable.
☆: 8 kgf or more ◎: 6 kgf or more and less than 8 kgf ○: 5 kgf or more and less than 6 kgf ×: Less than 5 kgf
　［崩壊性の判定基準］
　　崩壊時間が６０分未満であれば許容と判断した。
　　◎：崩壊時間が４０分未満
　　○：崩壊時間が４０分以上６０分未満
　　×：崩壊時間が６０分以上 [Degradation criteria]
If the disintegration time was less than 60 minutes, it was judged acceptable.
◎: Collapse time is less than 40 minutes ○: Collapse time is 40 minutes or more and less than 60 minutes ×: Collapse time is 60 minutes or more
　各実施例における配合比及び結果を、表１～表４に示す。 Tables 1 to 4 show the blending ratios and results in each example.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
〔表の脚注〕
※清酒酵母中の清酒酵母菌体（Ａ）としての量（清酒酵母菌体（Ａ）量＝清酒酵母量×０．７［乾燥質量］
各成分の含有量の単位：ｍｇ／錠 [Table footnotes]
* Amount of sake yeast cells (A) in sake yeast (amount of sake yeast cells (A) = amount of sake yeast x 0.7 [dry mass]
Unit of content of each component: mg / tablet
　表１～表４より明らかな通り、実施例１～１１の錠剤は、硬度及び崩壊性の両方とも良好であった。中でも、清酒酵母と二酸化ケイ素を事前混合した実施例６の錠剤は、硬度が非常に優れていた。一方、（Ｂ／Ａ）が０．７／１００未満である比較例１及び２の錠剤の硬度、及び（Ｂ／Ａ）が３８／１００を超える比較例３の錠剤の崩壊性は、実施例に比べて劣っていた。これらの結果は、本発明の錠剤が酵母濃度にかかわらず十分な錠剤物性を有することを示している。 As is clear from Tables 1 to 4, the tablets of Examples 1 to 11 were good in both hardness and disintegration. Among them, the tablet of Example 6 in which sake yeast and silicon dioxide were premixed was extremely excellent in hardness. On the other hand, the hardness of the tablets of Comparative Examples 1 and 2 where (B / A) is less than 0.7 / 100 and the disintegration property of the tablet of Comparative Example 3 where (B / A) exceeds 38/100 It was inferior to. These results indicate that the tablet of the present invention has sufficient tablet properties regardless of the yeast concentration.
〔処方例〕
＜錠剤１＞
　実施例６と同一の原料及び同様の方法で素錠を製造し、ヒドロキシプロピルメチルセルロース（メトローズ　ＳＥ－０６、信越化学工業（株）製）及びグリセリン（食品添加物グリセリン、阪本薬品工業（株）製）を水に溶解し、濃度５％のコーティング液を調製した。別途、コーティング機に素錠を仕込み、コーティング液を噴霧した。噴霧終了後、乾燥し、錠剤を得た。 [Prescription example]
<Tablet 1>
An uncoated tablet is produced by the same raw material and the same method as in Example 6, and hydroxypropylmethylcellulose (Metroise SE-06, manufactured by Shin-Etsu Chemical Co., Ltd.) and glycerin (food additive glycerin, Sakamoto Pharmaceutical Co., Ltd.) ) Was dissolved in water to prepare a coating solution having a concentration of 5%. Separately, uncoated tablets were charged into the coating machine and the coating liquid was sprayed. After spraying, the tablet was dried to obtain tablets.
（配合成分）　　　　　　　　　　　　　　　　（ｍｇ／錠）
　　清酒酵母（ＳＡＭｅ含有乾燥酵母、三菱ガス化学（株）製、酵母粉末中の菌体量７０％）（清酒酵母菌体（Ａ）の量）　１２０（８４）
　　微粒二酸化ケイ素（Ｂ）　　　　　　　　　　　２
　　結晶セルロース　　　　　　　　　　　　　１７０
　　カルボキシメチルセルロースカルシウム　　　　７
　　ステアリン酸カルシウム　　　　　　　　　　　１
　〔コーティング剤〕
　　　ヒドロキシプロピルメチルセルロース　　　　５
　　　グリセリン　　　　　　　　　　　　　　０．８
　（Ｂ／Ａ）　　　　　　　　　　　　　　　　２．４／１００ (Ingredients) (mg / tablet)
Sake yeast (SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in yeast powder) (amount of sake yeast (A)) 120 (84)
Fine silicon dioxide (B) 2
Crystalline cellulose 170
Carboxymethylcellulose calcium 7
Calcium stearate 1
〔Coating agent〕
Hydroxypropyl methylcellulose 5
Glycerin 0.8
(B / A) 2.4 / 100
＜錠剤２＞
　結晶セルロースの替わりに乳糖（Ｐｈａｒｍａｔｏｓｅ１００Ｍ、ＤＥＦ　Ｐｈａｒｍａ製）を用いた以外は実施例６と同一の原料及び同様の方法で錠剤を得た。
（配合成分）　　　　　　　　　　　　　　　（ｍｇ／錠）
　　清酒酵母（ＳＡＭｅ含有乾燥酵母、三菱ガス化学（株）製、酵母粉末中の菌体量７０％）（清酒酵母菌体（Ａ）の量）　１２０（８４）
　　微粒二酸化ケイ素（Ｂ）　　　　　　　　　　　２
　　乳糖　　　　　　　　　　　　　　　　　　１７０
　　カルボキシメチルセルロースカルシウム　　　　７
　　ステアリン酸カルシウム　　　　　　　　　　　１
　（Ｂ／Ａ）　　　　　　　　　　　　　　　　２．４／１００ <Tablet 2>
Tablets were obtained in the same manner as in Example 6 except that lactose (Pharmacatose 100M, manufactured by DEF Pharma) was used instead of crystalline cellulose.
(Ingredients) (mg / tablet)
Sake yeast (SAMe-containing dry yeast, manufactured by Mitsubishi Gas Chemical Co., Inc., 70% of the amount of cells in yeast powder) (amount of sake yeast (A)) 120 (84)
Fine silicon dioxide (B) 2
Lactose 170
Carboxymethylcellulose calcium 7
Calcium stearate 1
(B / A) 2.4 / 100

Claims (3)

  1. 　清酒酵母と二酸化ケイ素とを含有し、
    　清酒酵母菌体（Ａ）を錠剤１錠あたり１５質量％以上含有し、
    　清酒酵母菌体（Ａ）の含有量に対する二酸化ケイ素（Ｂ）の含有量の質量比率（Ｂ／Ａ）が０．７／１００以上３８／１００以下である
    錠剤。     Contains sake yeast and silicon dioxide,
    Containing at least 15% by mass of sake yeast (A) per tablet,
    The tablet whose mass ratio (B / A) of content of silicon dioxide (B) with respect to content of sake yeast (A) is 0.7 / 100 or more and 38/100 or less.
  2. 　清酒酵母と二酸化ケイ素（Ｂ）とをあらかじめ混合してから他の材料を添加混合して製造される、請求項１に記載の錠剤。 The tablet according to claim 1, which is produced by mixing sake yeast and silicon dioxide (B) in advance and then adding and mixing other materials.
  3. 　清酒酵母と二酸化ケイ素（Ｂ）とをあらかじめ混合してから他の材料を添加混合することを含む、請求項１又は２に記載の錠剤の製造方法。 The method for producing a tablet according to claim 1 or 2, comprising mixing sake yeast and silicon dioxide (B) in advance and then adding and mixing other materials.
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JPH1014533A (en) * 1996-06-27 1998-01-20 Asahi Breweries Ltd Lactobacillus-containing composition
JPH1045580A (en) * 1996-07-31 1998-02-17 Asahi Breweries Ltd Production of carnitine chloride-containing pharmaceutical preparation
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