WO2015190456A1 - Tablet containing sake yeast - Google Patents

Tablet containing sake yeast Download PDF

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Publication number
WO2015190456A1
WO2015190456A1 PCT/JP2015/066559 JP2015066559W WO2015190456A1 WO 2015190456 A1 WO2015190456 A1 WO 2015190456A1 JP 2015066559 W JP2015066559 W JP 2015066559W WO 2015190456 A1 WO2015190456 A1 WO 2015190456A1
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Prior art keywords
coating
tablet
sake yeast
yeast
tablets
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PCT/JP2015/066559
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French (fr)
Japanese (ja)
Inventor
大輔 金島
智夫 五木田
秀明 南埜
あゆみ 松野
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 CN201580028888.2A priority Critical patent/CN106456681B/en
Priority to JP2016527805A priority patent/JP6456377B2/en
Priority to KR1020167034060A priority patent/KR20170015315A/en
Publication of WO2015190456A1 publication Critical patent/WO2015190456A1/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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/282—Organic compounds, e.g. fats

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.
  • the yeast concentration in the tablet is increased, the bitterness derived from sake yeast and the generation of unique odors become problematic.
  • Patent Document 1 describes that a microbial dry cell tablet containing S-adenosyl-L-methionine (SAMe) is coated with a cellulose derivative, and a formulation example using hydroxypropylmethylcellulose as the cellulose derivative is described. ing.
  • SAMe S-adenosyl-L-methionine
  • Patent Document 1 is intended to stabilize the components contained in the yeast, and it has been difficult to prevent deterioration of coating properties such as peeling, turning, chipping and sticking.
  • the object of the present invention is to obtain a coating agent that is excellent in coating properties and has no problems in appearance, smell and taste.
  • the present inventors have intensively studied to solve the above problems.
  • the coating property can be kept good by using hydroxypropylmethylcellulose in combination with glycerin as a coating agent.
  • an external appearance, an odor, and a taste could be kept favorable by adjusting the balance of the coating rate of both hydroxypropyl methylcellulose and glycerin.
  • the present invention provides [1] to [3].
  • An uncoated tablet containing sake yeast is coated with a coating agent containing hydroxypropylmethylcellulose and glycerin, The ratio (A / B) of the coating rate (A) of hydroxypropylmethylcellulose to the coating rate (B) of glycerin is 2 to 20, The tablet containing sake yeast whose content of sake yeast (C) is 15 mass% or more with respect to the uncoated tablet.
  • the present invention it is possible to provide a coated tablet containing sake yeast that is excellent in coating properties and has no problems in appearance, smell, and taste.
  • 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 is usually 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 sake yeast (C) (dry mass) relative to the mass of the uncoated tablet of the present invention is usually 15% by mass or more based on the uncoated tablet as the content per sake yeast tablet, preferably It is 20 mass% or more, More preferably, it is 23 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, generation
  • the content of the sake yeast cell (C) per tablet is preferably 15% by mass to 70% by mass, more preferably 20% by mass to 60% by mass relative to the uncoated tablet. More preferably, it is from 50% by mass to 50% by mass.
  • Sake yeast cells (C) in the tablets of the present invention are contained in sake yeast.
  • the sake yeast and the sake yeast (C) may be the same.
  • components other than sake yeast (C) may be contained in sake yeast.
  • Examples of components other than the sake yeast (C) include fermentation broth and culture supernatant.
  • a plain tablet containing sake yeast is coated with a coating agent.
  • the coating agent contains hydroxypropyl methylcellulose and glycerin.
  • Hydroxypropylmethylcellulose (aka: HPMC) viscosity at 20 ° C. of a 2 wt% aqueous solution of is preferably 2 mm 2 / s or more, more preferably 4 mm 2 / s or more.
  • the upper limit is preferably 10 mm 2 / s or less, and more preferably 8 mm 2 / s or less.
  • the degree of substitution of hydroxypropylmethylcellulose is preferably 15% or more, and more preferably 20% or more, with a methoxy group content.
  • the upper limit is preferably 40% or less, and more preferably 30% or less.
  • the hydroxypropoxy group content is preferably 2% or more, and more preferably 5% or more.
  • the upper limit is preferably 15% or less, and more preferably 12% or less.
  • hydroxypropylmethylcellulose examples include METROSE 60SH-03, 60SH-06, SE-06, MCE-4, SB-4, SM-4, TC-5E, TC-5M, manufactured by Shin-Etsu Chemical Co., Ltd. TC-5R etc. are mentioned. Of these, SE-06 and TC-5R are particularly preferable.
  • the coating rate (A) of hydroxypropylmethylcellulose is preferably 0.5% or more, and more preferably 1% or more.
  • the upper limit is preferably 10% or less, more preferably 5% or less, and still more preferably 3% or less.
  • the coating rate is preferably 0.5% to 10%, more preferably 0.5% to 5%, still more preferably 1% to 3%.
  • glycerin As glycerin, glycerin prescribed in the Japanese Pharmacopoeia or the Food Addendum can be used.
  • the coating ratio (B) of glycerin is preferably 0.025% or more, and more preferably 0.1% or more.
  • the upper limit is preferably 2.5% or less, and more preferably 0.8% or less.
  • the coating rate is preferably 0.025% to 2.5%, and more preferably 0.1% to 0.8%. If the coating ratio (B) of glycerin is equal to or higher than the preferable lower limit value, the coating property can be kept better, and if it is equal to or lower than the preferable upper limit value, the appearance change with time is less likely to occur.
  • the coating rate is a numerical value calculated by the following equation.
  • ⁇ formula ⁇ Coating rate (content of coating component / mass of uncoated tablet) ⁇ 100
  • the ratio (A / B) of the coating rate (A) of hydroxypropylmethylcellulose to the coating rate (B) of glycerin in the tablet is 2 or more, and preferably 4 or more.
  • the upper limit is 20 or less, and preferably 10 or less.
  • the ratio is 2 to 20, and preferably 4 to 10.
  • the coating agent may contain components other than hydroxypropylmethylcellulose and glycerin.
  • the component include synthetic polymers such as polyvinyl alcohol and polyvinyl pyrrolidone, polyhydric alcohols such as polyethylene glycol, propylene glycol and glycerin, synthetic esters such as triacetin, triethyl citrate and glycerin fatty acid ester, carmellose, hydroxypropyl cellulose, Examples thereof include celluloses such as methylcellulose and ethylcellulose, natural substances such as shellac, pullulan and gum arabic, or combinations thereof.
  • pigments such as a titanium oxide and an iron oxide, mannitol, cetanol, and sodium lauryl sulfate as needed.
  • carnauba wax or the like can be added as a brightening agent after film coating.
  • any components used in the manufacture of tablets such as other pharmaceuticals, quasi drugs, foods, etc. in an amount that does not impair the effects of the present invention. Also good.
  • 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, magnesium carbonate, calcium carbonate, purified sucrose, glucose, hydrous glucose, lactose, silicon dioxide (also known as silicic anhydride, fine silicon dioxide), Examples include low-substituted hydroxypropylcellulose.
  • 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, carboxymethylcellulose calcium, 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, 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.
  • foaming agent examples include baking soda.
  • the manufacturing method of the tablet of the present invention is not particularly limited, but will be described below with an example.
  • the uncoated tablets may be granulated using a method such as wet granulation or dry granulation.
  • a method such as wet granulation or dry granulation.
  • by direct tableting method in which raw material of tablet is mixed and tableted, it is made into dry granule by compression molding, or after adding mixed solvent of water and kneading, granulating and drying to make wet granule
  • an additive may be dissolved in a solvent such as water and spray-dried to obtain wet granules, and then an uncoated tablet may be obtained by an indirect tableting method in which a compressed tablet is produced or a combination thereof.
  • the surface of the uncoated tablet is prepared by blending hydroxypropylmethylcellulose, glycerin and a desired optional component to prepare a coating solution, spraying the coating solution on the uncoated tablet as it is, or spraying a coating solution containing water and drying.
  • the tablet of the present invention can be obtained by forming a coating film on the tablet.
  • Examples 1 to 14 and Comparative Examples 1 and 2 [Uncoated tablets 1 and 2] In producing sake yeast tablets in each Example, uncoated tablets 1 and 2 were prepared as coating targets. The composition of the uncoated tablet is shown in Table 1.
  • the manufacturing method of the uncoated tablets was as follows. 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 (Ceorus (registered trademark) UF-F711, manufactured by Asahi Kasei Chemicals Corporation), carboxymethylcellulose calcium (ECG-FA, manufactured by Nichirin Chemical Industries, Ltd.) were added and mixed, and then calcium stearate (stear Calcium phosphate and Taihei Chemical Sangyo Co., Ltd.) were added and mixed, and tableted with 12 kgN by the direct tableting method. A rotary tableting machine (LIBRA2, manufactured by Kikusui Seisakusho Co., Ltd.) was used for tableting.
  • 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 F
  • the coating agents shown in Tables 2 to 4 were dissolved in water to prepare a coating solution having a concentration of 5%.
  • 200 kg of uncoated tablets are charged in a coating machine (DRC-14000S, manufactured by POWREC Co., Ltd.), preheated to an exhaust temperature of 45 ° C at an air supply temperature of 65 ° C and a rotation speed of 1 rpm, and then a rotation speed of 5 rpm and a spray liquid speed of 300 mL.
  • the coating solution was sprayed at / min. After spraying, the coating was dried after drying to an exhaust temperature of 50 ° C.
  • hydroxypropyl methylcellulose (trade name: Metrolose SE-06, manufacturer name: Shin-Etsu Chemical Co., Ltd.) used in each example had the following properties: viscosity of 2% by weight aqueous solution at 20 ° C. 5 .9 mm 2 / s; methoxy group content 28.9%; hydroxypropoxy group content 9.0%.
  • glycerin food additive glycerin manufactured by Sakamoto Pharmaceutical Co., Ltd. was used.
  • the coating property, appearance, smell and taste of each obtained tablet were evaluated.
  • the coating property was evaluated by visually observing the state of peeling, turning, and chipping of a tablet immediately after production, and evaluating it according to the following criteria.
  • the appearance of the tablet was evaluated by visually observing the change in the outer color of the tablet stored for 4 months in a constant temperature bath at 40 ° C., and evaluated based on the following criteria.
  • the evaluation of smell and taste was evaluated according to the following criteria from the evaluation of smell and taste by five panelists in the tablets immediately after production.
  • ⁇ 0 tablets out of 100 tablets in which peeling, turning, and chipping are recognized
  • ⁇ Tablets in which peeling, turning, and chipping are observed are 1 tablet or more and 2 tablets or less in 100 tablets
  • ⁇ peeling, turning, and chipping
  • the number of recognized tablets is 3 or more and 5 or less in 100 tablets.
  • X The number of tablets in which peeling, turning, or chipping is observed is 6 or more in 100 tablets.
  • Tables 2 to 4 show the types of uncoated tablets, coating conditions, and evaluation results in each Example and Comparative Example.
  • the tablets of Examples 1 to 14 both had good coating properties and appearance, and the odor and taste were within the allowable range.
  • the coating agent of Comparative Example 1 having an A / B of less than 2 is inferior in coating properties, appearance, smell and taste
  • the coating agent of Comparative Example 2 having an A / B of more than 20 is coating property, smell and It was inferior in taste. This result shows that the tablet of the present invention is excellent in coating property, has no problem in appearance, and has a satisfactory smell and taste.

Abstract

　The purpose of the present invention is to obtain a coating agent that has excellent coating characteristics and is problem-free in terms of appearance, odor and flavor. The present invention provides a tablet containing sake yeast, said tablet being coated with a coating agent containing hydroxypropyl methylcellulose and glycerol. The ratio (A/B) of the coating percentage (A) of the hydroxypropyl methylcellulose to the coating percentage (B) of the glycerol is 2 to 20, and the content of sake yeast cells (C) is 15 mass% with respect to an uncoated tablet.

Description

清酒酵母を含有する錠剤Tablets containing sake yeast
　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。しかし、錠剤中の酵母濃度を高めると、清酒酵母由来の苦味、特有なにおいの発生が問題となる。 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. However, when the yeast concentration in the tablet is increased, the bitterness derived from sake yeast and the generation of unique odors become problematic.
　このような苦味、においを抑制する技術として、コーティング剤により錠剤をコーティングする技術がある。特許文献１には、Ｓ－アデノシル－Ｌ－メチオニン（ＳＡＭｅ）を含有する微生物乾燥菌体の錠剤をセルロース誘導体でコーティングすることが記載され、セルロース誘導体としてヒドロキシプロピルメチルセルロースを用いた製剤例が記載されている。 As a technique for suppressing such bitterness and smell, there is a technique for coating tablets with a coating agent. Patent Document 1 describes that a microbial dry cell tablet containing S-adenosyl-L-methionine (SAMe) is coated with a cellulose derivative, and a formulation example using hydroxypropylmethylcellulose as the cellulose derivative is described. ing.
国際公開第２００９／０８１８３３号International Publication No. 2009/081833
　しかし、特許文献１に記載の方法は、酵母に含まれる成分を安定化させることを目的としており、はがれ、めくれ、欠け、スティッキングが生じる等コーティング性の悪化を防ぐことが難しかった。 However, the method described in Patent Document 1 is intended to stabilize the components contained in the yeast, and it has been difficult to prevent deterioration of coating properties such as peeling, turning, chipping and sticking.
　本発明は、コーティング性に優れ、外観、におい及び味の面でも問題のないコーティング剤を得ることを目的とする。 The object of the present invention is to obtain a coating agent that is excellent in coating properties and has no problems in appearance, smell and taste.
　本発明者らは上記課題を解決すべく鋭意検討を重ねた。その過程で、ヒドロキシプロピルメチルセルロースをグリセリンと組み合わせてコーティング剤として用いることで、コーティング性を良好に保つことができることを見出した。さらに、ヒドロキシプロピルメチルセルロースとグリセリンの、両者のコーティング率のバランスを調整することで、外観、におい、味も良好に保つことができることを見出した。 The present inventors have intensively studied to solve the above problems. In the process, it was found that the coating property can be kept good by using hydroxypropylmethylcellulose in combination with glycerin as a coating agent. Furthermore, it discovered that an external appearance, an odor, and a taste could be kept favorable by adjusting the balance of the coating rate of both hydroxypropyl methylcellulose and glycerin.
　本発明は、〔１〕～〔３〕を提供する。
〔１〕清酒酵母を含有する素錠が、ヒドロキシプロピルメチルセルロース及びグリセリンを含むコーティング剤によってコーティングされており、
　ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）のグリセリンのコーティング率（Ｂ）に対する比率（Ａ／Ｂ）が２～２０であり、
　清酒酵母菌体（Ｃ）の含有量が素錠に対し１５質量％以上である、清酒酵母を含有する錠剤。
〔２〕グリセリンのコーティング率（Ｂ）が、０．０２５％～２．５％である、〔１〕に記載の錠剤。
〔３〕ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）が、０．５％以上である、〔１〕又は〔２〕に記載の錠剤。 The present invention provides [1] to [3].
[1] An uncoated tablet containing sake yeast is coated with a coating agent containing hydroxypropylmethylcellulose and glycerin,
The ratio (A / B) of the coating rate (A) of hydroxypropylmethylcellulose to the coating rate (B) of glycerin is 2 to 20,
The tablet containing sake yeast whose content of sake yeast (C) is 15 mass% or more with respect to the uncoated tablet.
[2] The tablet according to [1], wherein the coating ratio (B) of glycerin is 0.025% to 2.5%.
[3] The tablet according to [1] or [2], wherein the coating rate (A) of hydroxypropylmethylcellulose is 0.5% or more.
　本発明によれば、コーティング性に優れ、外観、におい、味の面で問題のない清酒酵母を含有するコーティング錠剤を提供することができる。 According to the present invention, it is possible to provide a coated tablet containing sake yeast that is excellent in coating properties and has no problems in appearance, smell, and taste.
　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、通常は乾燥菌体である。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 is usually 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.
　本発明の素錠の質量に対する清酒酵母菌体（Ｃ）（乾燥質量）の含有量は、清酒酵母の錠剤１錠あたりの含有量として、素錠に対し通常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、清酒酵母由来の苦味、特有なにおいの発生を防ぎ、味及びにおいを保持することができる。清酒酵母菌体（Ｃ）の錠剤１錠あたりの含有量は、素錠に対し、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 sake yeast (C) (dry mass) relative to the mass of the uncoated tablet of the present invention is usually 15% by mass or more based on the uncoated tablet as the content per sake yeast tablet, preferably It is 20 mass% or more, More preferably, it is 23 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, generation | occurrence | production of the bitter taste derived from sake yeast and a peculiar smell can be prevented, and a taste and smell can be hold | maintained. The content of the sake yeast cell (C) per tablet is preferably 15% by mass to 70% by mass, more preferably 20% by mass to 60% by mass relative to the uncoated tablet. More preferably, it is from 50% by mass to 50% by mass.
　本発明の錠剤における清酒酵母菌体（Ｃ）は、清酒酵母中に含有される。清酒酵母と清酒酵母菌体（Ｃ）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（Ｃ）以外の成分が含有されていてもよい。当該清酒酵母菌体（Ｃ）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 (C) in the tablets of the present invention are contained in sake yeast. The sake yeast and the sake yeast (C) may be the same. Moreover, components other than sake yeast (C) may be contained in sake yeast. Examples of components other than the sake yeast (C) include fermentation broth and culture supernatant.
　本発明の錠剤は、清酒酵母を含有する素錠がコーティング剤によってコーティングされている。コーティング剤は、ヒドロキシプロピルメチルセルロース及びグリセリンを含む。 In the tablet of the present invention, a plain tablet containing sake yeast is coated with a coating agent. The coating agent contains hydroxypropyl methylcellulose and glycerin.
　ヒドロキシプロピルメチルセルロース（別名：ＨＰＭＣ）の２質量％水溶液の２０℃における粘度は、２ｍｍ2／ｓ以上であることが好ましく、４ｍｍ2／ｓ以上であることがより好ましい。上限は、１０ｍｍ2／ｓ以下であることが好ましく、８ｍｍ2／ｓ以下であることがより好ましい。これにより、フィルム成形性の良好なコーティングが可能となる。 Hydroxypropylmethylcellulose (aka: HPMC) viscosity at 20 ° C. of a 2 wt% aqueous solution of is preferably 2 mm 2 / s or more, more preferably 4 mm 2 / s or more. The upper limit is preferably 10 mm 2 / s or less, and more preferably 8 mm 2 / s or less. Thereby, the coating with favorable film moldability becomes possible.
　ヒドロキシプロピルメチルセルロースの置換度は、メトキシ基含量が１５％以上であることが好ましく、２０％以上であることがより好ましい。上限は、４０％以下であることが好ましく、３０％以下であることがより好ましい。また、ヒドロキシプロポキシ基含量が２％以上であることが好ましく、５％以上であることがより好ましい。上限は、１５％以下であることが好ましく、１２％以下であることがより好ましい。これにより、フィルム成形性の良好なコーティングが可能となる。 The degree of substitution of hydroxypropylmethylcellulose is preferably 15% or more, and more preferably 20% or more, with a methoxy group content. The upper limit is preferably 40% or less, and more preferably 30% or less. Further, the hydroxypropoxy group content is preferably 2% or more, and more preferably 5% or more. The upper limit is preferably 15% or less, and more preferably 12% or less. Thereby, the coating with favorable film moldability becomes possible.
　ヒドロキシプロピルメチルセルロースとしては、信越化学工業（株）製のメトローズ（ＭＥＴＲＯＳＥ）６０ＳＨ－０３、６０ＳＨ－０６、ＳＥ－０６、ＭＣＥ－４、ＳＢ－４、ＳＭ－４、ＴＣ－５Ｅ、ＴＣ－５Ｍ、ＴＣ－５Ｒなどが挙げられる。このうち、特にＳＥ－０６、ＴＣ－５Ｒが好ましい。 Examples of hydroxypropylmethylcellulose include METROSE 60SH-03, 60SH-06, SE-06, MCE-4, SB-4, SM-4, TC-5E, TC-5M, manufactured by Shin-Etsu Chemical Co., Ltd. TC-5R etc. are mentioned. Of these, SE-06 and TC-5R are particularly preferable.
　ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）は、０．５％以上であることが好ましく、１％以上であることがより好ましい。上限は、１０％以下であることが好ましく、５％以下であることがより好ましく、３％以下であることが更に好ましい。該コーティング率は、０．５％～１０％であることが好ましく、０．５％～５％であることがより好ましく、１％～３％であることが更に好ましい。
　ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）が、好ましい下限値以上であると、清酒酵母由来の苦味、特有なにおいがより低減され、好ましい上限値以下であれば、崩壊性がより良好な錠剤が得られる。 The coating rate (A) of hydroxypropylmethylcellulose is preferably 0.5% or more, and more preferably 1% or more. The upper limit is preferably 10% or less, more preferably 5% or less, and still more preferably 3% or less. The coating rate is preferably 0.5% to 10%, more preferably 0.5% to 5%, still more preferably 1% to 3%.
When the hydroxypropylmethylcellulose coating rate (A) is at least the preferred lower limit, the bitterness and unique odor derived from sake yeast are further reduced, and if it is below the preferred upper limit, a tablet with better disintegration is obtained. It is done.
　グリセリンとしては、日本薬局方又は食品添加物公定書に規定のグリセリンを用いることができる。 As glycerin, glycerin prescribed in the Japanese Pharmacopoeia or the Food Addendum can be used.
　グリセリンのコーティング率（Ｂ）は、０．０２５％以上であることが好ましく、０．１％以上であることがより好ましい。上限は、２．５％以下であることが好ましく、０．８％以下であることがより好ましい。該コーティング率は、０．０２５％～２．５％であることが好ましく、０．１％～０．８％であることがより好ましい。
　グリセリンのコーティング率（Ｂ）が、好ましい下限値以上であると、コーティング性をより良好に保つこことができ、好ましい上限値以下であれば、経時的な外観変化がより発生しにくくなる。 The coating ratio (B) of glycerin is preferably 0.025% or more, and more preferably 0.1% or more. The upper limit is preferably 2.5% or less, and more preferably 0.8% or less. The coating rate is preferably 0.025% to 2.5%, and more preferably 0.1% to 0.8%.
If the coating ratio (B) of glycerin is equal to or higher than the preferable lower limit value, the coating property can be kept better, and if it is equal to or lower than the preferable upper limit value, the appearance change with time is less likely to occur.
　本発明においてコーティング率は、以下の式で算出される数値である。 In the present invention, the coating rate is a numerical value calculated by the following equation.
〔式〕
　コーティング率＝（コーティング成分の含有量／素錠の質量）×１００ 〔formula〕
Coating rate = (content of coating component / mass of uncoated tablet) × 100
　錠剤中の、ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）のグリセリンのコーティング率（Ｂ）に対する比率（Ａ／Ｂ）は、２以上であり、４以上であることが好ましい。上限は、２０以下であり、１０以下であることが好ましい。該比率は、２～２０であり、４～１０であることが好ましい。
　（Ａ／Ｂ）が、好ましい下限値以上及び上限値以下であると、コーティング性をより良好に保つこことができる。 The ratio (A / B) of the coating rate (A) of hydroxypropylmethylcellulose to the coating rate (B) of glycerin in the tablet is 2 or more, and preferably 4 or more. The upper limit is 20 or less, and preferably 10 or less. The ratio is 2 to 20, and preferably 4 to 10.
When (A / B) is not less than the preferable lower limit value and not more than the upper limit value, the coating property can be kept better.
　コーティング剤は、ヒドロキシプロピルメチルセルロース及びグリセリン以外の成分を含んでいてもよい。該成分としては、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、カルメロース、ヒドロキシプロピルセルロース、メチルセルロース、エチルセルロース等のセルロース類、シェラック、プルラン、アラビアゴム等の天然物質、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、光沢化剤としてカルナバロウ等を加えることもできる。 The coating agent may contain components other than hydroxypropylmethylcellulose and glycerin. Examples of the component include synthetic polymers such as polyvinyl alcohol and polyvinyl pyrrolidone, polyhydric alcohols such as polyethylene glycol, propylene glycol and glycerin, synthetic esters such as triacetin, triethyl citrate and glycerin fatty acid ester, carmellose, hydroxypropyl cellulose, Examples thereof include celluloses such as methylcellulose and ethylcellulose, natural substances such as shellac, pullulan and gum arabic, 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. In addition, carnauba wax or the like can be added as a brightening agent after film coating.
　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られてい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 it does not adversely affect the effects of the present invention, it contains any components used in the manufacture of tablets such as other pharmaceuticals, quasi drugs, foods, etc. in an amount that does not impair the effects of the present invention. Also good. 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、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、二酸化ケイ素（別名：無水ケイ酸、微粒二酸化ケイ素）、低置換度ヒドロキシプロピルセルロースなどが挙げられる。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, magnesium carbonate, calcium carbonate, purified sucrose, glucose, hydrous glucose, lactose, silicon dioxide (also known as silicic anhydride, fine silicon dioxide), Examples include low-substituted hydroxypropylcellulose. 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カルシウム、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％であることが更に好ましい。 Examples of the binder include sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium, 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、０．１～３０質量％が好ましく、１～２０質量％であることが更に好ましい。 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, 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、軽質無水ケイ酸などが挙げられる。 Examples of the antistatic agent and the disintegration extender include light anhydrous silicic acid.
　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.
　本発明の錠剤の製造方法は特に限定されないが、以下に一例を挙げて説明する。まず、素錠を得る。必要に応じて湿式造粒、乾式造粒等の方法を用いて素錠を造粒してもよい。また、素錠の原料を混合して打錠する直接打錠法により、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により、またはこれらを組合せた方法により、素錠を得てもよい。次に、ヒドロキシプロピルメチルセルロース、グリセリン及び所望の任意成分を配合してコーティング液を調製し、素錠にコーティング液をそのまま、又は水を加えたコーティング溶液を噴霧し、乾燥することにより素錠の表面にコーティング膜を形成させることにより本発明の錠剤を得ることができる。 The manufacturing method of the tablet of the present invention is not particularly limited, but will be described below with an example. First, get an uncoated tablet. If necessary, the uncoated tablets may be granulated using a method such as wet granulation or dry granulation. In addition, by direct tableting method in which raw material of tablet is mixed and tableted, it is made into dry granule by compression molding, or after adding mixed solvent of water and kneading, granulating and drying to make wet granule Alternatively, an additive may be dissolved in a solvent such as water and spray-dried to obtain wet granules, and then an uncoated tablet may be obtained by an indirect tableting method in which a compressed tablet is produced or a combination thereof. Next, the surface of the uncoated tablet is prepared by blending hydroxypropylmethylcellulose, glycerin and a desired optional component to prepare a coating solution, spraying the coating solution on the uncoated tablet as it is, or spraying a coating solution containing water and drying. The tablet of the present invention can be obtained by forming a coating film on the tablet.
　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１～１４及び比較例１及び２
〔素錠１及び２〕
　各実施例における清酒酵母錠剤を製造するにあたり、コーティングの対象としての素錠１及び２を作成した。素錠の組成を表１に示す。 Examples 1 to 14 and Comparative Examples 1 and 2
[Uncoated tablets 1 and 2]
In producing sake yeast tablets in each Example, uncoated tablets 1 and 2 were prepared as coating targets. The composition of the uncoated tablet is shown in Table 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
〔表１中の脚注〕
※清酒酵母中の清酒酵母菌体（Ｃ）としての量（清酒酵母菌体（Ｃ）量＝清酒酵母量×０．７）［乾燥質量］
　各成分の含有量の単位：ｍｇ／錠 [Footnotes in Table 1]
* Amount of sake yeast cells (C) in sake yeast (Sake yeast cells (C) amount = amount of sake yeast x 0.7) [dry mass]
Unit of content of each component: mg / tablet
　素錠の製造方法は以下のとおりとした。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％）及び微粒二酸化ケイ素（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）、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、直接打錠法により１２ｋｇＮ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。 The manufacturing method of the uncoated tablets was as follows. 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 (Ceorus (registered trademark) UF-F711, manufactured by Asahi Kasei Chemicals Corporation), carboxymethylcellulose calcium (ECG-FA, manufactured by Nichirin Chemical Industries, Ltd.) were added and mixed, and then calcium stearate (stear Calcium phosphate and Taihei Chemical Sangyo Co., Ltd.) were added and mixed, and tableted with 12 kgN by the direct tableting method. A rotary tableting machine (LIBRA2, manufactured by Kikusui Seisakusho Co., Ltd.) was used for tableting.
　表２～４中のコーティング剤を水に溶解し、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（ＤＲＣ－１４０００Ｓ、（株）パウレック製）に、素錠２００ｋｇを仕込み、給気温度６５℃、回転数１ｒｐｍで、排気温度４５℃まで予熱後、回転数５ｒｐｍ・噴霧液速度３００ｍＬ／ｍｉｎでコーティング液を噴霧した。噴霧終了後、排気温度５０℃まで乾燥し、コーティングを終了した。なお、各実施例で用いたヒドロキシプロピルメチルセルロース（商品名：メトローズＳＥ－０６、メーカー名：信越化学工業（株））は以下の性質を有していた：２質量％水溶液の２０℃における粘度５．９ｍｍ2／ｓ；メトキシ基含量２８．９％；ヒドロキシプロポキシ基含量９．０％。また、グリセリンは、食品添加物グリセリン、阪本薬品工業（株）製を用いた。 The coating agents shown in Tables 2 to 4 were dissolved in water to prepare a coating solution having a concentration of 5%. Separately, 200 kg of uncoated tablets are charged in a coating machine (DRC-14000S, manufactured by POWREC Co., Ltd.), preheated to an exhaust temperature of 45 ° C at an air supply temperature of 65 ° C and a rotation speed of 1 rpm, and then a rotation speed of 5 rpm and a spray liquid speed of 300 mL. The coating solution was sprayed at / min. After spraying, the coating was dried after drying to an exhaust temperature of 50 ° C. In addition, hydroxypropyl methylcellulose (trade name: Metrolose SE-06, manufacturer name: Shin-Etsu Chemical Co., Ltd.) used in each example had the following properties: viscosity of 2% by weight aqueous solution at 20 ° C. 5 .9 mm 2 / s; methoxy group content 28.9%; hydroxypropoxy group content 9.0%. As glycerin, food additive glycerin manufactured by Sakamoto Pharmaceutical Co., Ltd. was used.
　得られた各錠剤のコーティング性、外観、におい及び味を評価した。コーティング性の評価は、製造直後の錠剤におけるコーティングのはがれ、めくれ、欠けの状況を目視にて観察し、以下に示す基準で評価した。錠剤の外観の評価は、４０℃の恒温槽にて４ヶ月間保存した錠剤における外側の色の変化の状況を目視にて観察し、以下に示す基準で評価した。におい及び味の評価は、製造直後の錠剤におけるパネラー５人によるにおい・味の評価から、以下に示す基準により評価した。 The coating property, appearance, smell and taste of each obtained tablet were evaluated. The coating property was evaluated by visually observing the state of peeling, turning, and chipping of a tablet immediately after production, and evaluating it according to the following criteria. The appearance of the tablet was evaluated by visually observing the change in the outer color of the tablet stored for 4 months in a constant temperature bath at 40 ° C., and evaluated based on the following criteria. The evaluation of smell and taste was evaluated according to the following criteria from the evaluation of smell and taste by five panelists in the tablets immediately after production.
　［コーティング性の判定基準］
　コーティングのはがれ、めくれ、欠けが認められる錠剤が、１００錠中２錠以下であれば許容と判断した。
　◎：はがれ、めくれ、欠けが認められる錠剤が１００錠中０錠である
　○：はがれ、めくれ、欠けが認められる錠剤が１００錠中１錠以上２錠以下である
　△：はがれ、めくれ、欠けが認められる錠剤が１００錠中３錠以上５錠以下である
　×：はがれ、めくれ、欠けが認められる錠剤が１００錠中６錠以上である [Criteria for coating properties]
The coating was judged to be acceptable if there were no more than 2 tablets out of 100 tablets with peeling, turning and chipping.
◎: 0 tablets out of 100 tablets in which peeling, turning, and chipping are recognized ○: Tablets in which peeling, turning, and chipping are observed are 1 tablet or more and 2 tablets or less in 100 tablets △: peeling, turning, and chipping The number of recognized tablets is 3 or more and 5 or less in 100 tablets. X: The number of tablets in which peeling, turning, or chipping is observed is 6 or more in 100 tablets.
　［外観の判定基準］
　４０℃４ヶ月保存品が冷暗所（５℃）保存品と比べて外観の色の変化が殆ど無ければ許容と判断した。
　◎：外観の色の変化が無い
　○：外観の色の変化が殆ど無い
　△：外観の色の変化が弱く認められる
　×：外観の色の変化が強く認められる [Appearance criteria]
A product stored at 40 ° C. for 4 months was judged to be acceptable if there was almost no change in appearance color compared to a product stored in a cool dark place (5 ° C.).
◎: No change in appearance color ○: Little change in appearance color △: A slight change in appearance color is recognized ×: A strong change in appearance color is recognized
　［におい及び味の判定基準］
　パネラー５人の平均点が４点を上回れば許容と判断した。
　５点：におい・味を感じなかった
　４点：ややにおい・味を感じた
　３点：におい・味を感じた
　２点：かなりにおい・味を感じた
　１点：非常ににおい・味を感じた
　＜評価＞
　◎：平均点が４．５点を上回る
　○：平均点が４点を上回り、４．５点以下
　△：平均点が３点を上回り、４点以下
　×：平均点が３点以下 [Odor and taste criteria]
If the average score of 5 panelists exceeded 4 points, it was judged acceptable.
5 points: I did not feel the smell / taste 4 points: I felt some smell / taste 3 points: I felt smell / taste 2 points: I felt quite smell / taste 1 point: I felt very smell / taste <Evaluation>
◎: Average score exceeds 4.5 points ○: Average score exceeds 4 points, 4.5 points or less △: Average score exceeds 3 points, 4 points or less ×: Average score is 3 points or less
　各実施例および比較例における素錠の種類、コーティング条件及び評価結果を、表２～４に示す。 Tables 2 to 4 show the types of uncoated tablets, coating conditions, and evaluation results in each Example and Comparative Example.
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２～４より明らかなとおり、実施例１～１４の錠剤は、コーティング性及び外観のいずれも良好な評価であり、におい及び味も許容範囲内であった。これに対し、Ａ／Ｂが２未満である比較例１のコーティング剤は、コーティング性、外観、におい及び味に劣り、Ａ／Ｂが２０を超える比較例２のコーティング剤はコーティング性、におい及び味に劣っていた。この結果は、本発明の錠剤がコーティング性に優れ、外観にも問題がなく、におい、味についても申し分ないことを示している。 As is clear from Tables 2 to 4, the tablets of Examples 1 to 14 both had good coating properties and appearance, and the odor and taste were within the allowable range. On the other hand, the coating agent of Comparative Example 1 having an A / B of less than 2 is inferior in coating properties, appearance, smell and taste, and the coating agent of Comparative Example 2 having an A / B of more than 20 is coating property, smell and It was inferior in taste. This result shows that the tablet of the present invention is excellent in coating property, has no problem in appearance, and has a satisfactory smell and taste.
〔処方例〕
＜錠剤＞
　各成分の配合量以外は実施例１と同様の方法で錠剤を得た。表５に錠剤の組成を示す。 [Prescription example]
<Tablets>
A tablet was obtained in the same manner as in Example 1 except for the amount of each component. Table 5 shows the composition of the tablets.
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005

Claims (3)

  1. 　清酒酵母を含有する素錠が、ヒドロキシプロピルメチルセルロース及びグリセリンを含むコーティング剤によってコーティングされており、
    　ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）のグリセリンのコーティング率（Ｂ）に対する比率（Ａ／Ｂ）が２～２０であり、
    　清酒酵母菌体（Ｃ）の含有量が素錠に対し１５質量％以上である、錠剤。     An uncoated tablet containing sake yeast is coated with a coating agent containing hydroxypropylmethylcellulose and glycerin,
    The ratio (A / B) of the coating rate (A) of hydroxypropylmethylcellulose to the coating rate (B) of glycerin is 2 to 20,
    The tablet whose content of sake yeast (C) is 15 mass% or more with respect to the uncoated tablet.
  2. 　グリセリンのコーティング率（Ｂ）が、０．０２５％～２．５％である、請求項１に記載の錠剤。 The tablet according to claim 1, wherein the coating ratio (B) of glycerin is 0.025% to 2.5%.
  3. 　ヒドロキシプロピルメチルセルロースのコーティング率（Ａ）が、０．５％以上である、請求項１又は２に記載の錠剤。 The tablet according to claim 1 or 2, wherein the hydroxypropylmethylcellulose coating rate (A) is 0.5% or more.
PCT/JP2015/066559 2014-06-10 2015-06-09 Tablet containing sake yeast WO2015190456A1 (en)

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