JP7475824B2 - Composition - Google Patents
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- JP7475824B2 JP7475824B2 JP2019139301A JP2019139301A JP7475824B2 JP 7475824 B2 JP7475824 B2 JP 7475824B2 JP 2019139301 A JP2019139301 A JP 2019139301A JP 2019139301 A JP2019139301 A JP 2019139301A JP 7475824 B2 JP7475824 B2 JP 7475824B2
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/221—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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Description
本発明は、メチルメチオニンスルホニウムクロライドを含有する組成物等に関する。 The present invention relates to a composition containing methylmethionine sulfonium chloride.
メチルメチオニンスルホニウムクロライド（以下、「ＭＭＳＣ」と称することもある。）は、消化管粘膜保護作用を有することから、胃潰瘍、十二指腸潰瘍、胃炎等の自覚症状及び他覚所見の改善、慢性肝疾患における肝機能の改善等に用いられ、また、胃腸薬の成分として広く利用されている。
しかし、ＭＭＳＣは不安定であり、経時的に含量低下が生じ易い。従って、ＭＭＳＣを含有する組成物には、経時的な品質低下等の問題があった。
Methylmethionine sulfonium chloride (hereinafter sometimes referred to as "MMSC") has a gastrointestinal mucosa-protecting effect and is therefore used to improve subjective symptoms and objective findings of gastric ulcers, duodenal ulcers, gastritis, etc., and to improve liver function in chronic liver diseases, and is also widely used as an ingredient in gastrointestinal medicines.
However, MMSCs are unstable and the content is likely to decrease over time, and therefore compositions containing MMSCs have problems such as deterioration in quality over time.
組成物中のＭＭＳＣの安定化手段としては例えば、ＭＭＳＣとビタミンＢ１若しくはその誘導体又はそれらの塩とを同一製剤中に含有せしめる手段（特許文献１）、ＭＭＳＣを含有する素錠にプロテクト掛けを施した後、さらにコハク化ゼラチンを含有する糖衣用組成液でコーティングして糖衣製剤とする手段（特許文献２）、ＭＭＳＣにシリコーンを混合させて得た混合末を用いる手段（特許文献３）、ＭＭＳＣを含む芯材、並びに該芯材を被覆する糖衣層を有する糖衣製剤であって、該糖衣層の少なくとも１つに、糖及びアクリル酸エチル・メタクリル酸メチルコポリマー０．０１～１０重量％を含む糖衣製剤とする手段（特許文献４）等が知られている。 Known methods for stabilizing MMSC in a composition include, for example, a method in which MMSC and vitamin B1 or a derivative thereof, or a salt thereof, are incorporated into the same preparation (Patent Document 1), a method in which a plain tablet containing MMSC is protected and then further coated with a sugar-coating composition liquid containing succinated gelatin to produce a sugar-coated preparation (Patent Document 2), a method using a mixed powder obtained by mixing MMSC with silicone (Patent Document 3), and a method in which a sugar-coated preparation has a core material containing MMSC and sugar-coating layers that coat the core material, at least one of which contains sugar and 0.01 to 10% by weight of ethyl acrylate-methyl methacrylate copolymer (Patent Document 4).
本発明の課題は、組成物中のメチルメチオニンスルホニウムクロライドを安定化する新たな手段を提供することにある。 The object of the present invention is to provide a new means for stabilizing methylmethionine sulfonium chloride in a composition.
本発明者は、斯かる実情に鑑み鋭意研究した結果、驚くべきことに、コウボク及びその抽出物よりなる群から選ばれる１種以上（以下、「成分（Ｂ）」と称することもある。）が、メチルメチオニンスルホニウムクロライド（以下、「成分（Ａ）」と称することもある。）の含量低下を抑制し、これを安定化する作用を有することを見出し、本発明を完成した。 In light of this situation, the inventors conducted extensive research and surprisingly discovered that one or more members selected from the group consisting of magnolia bark and its extracts (hereinafter sometimes referred to as "component (B)") have the effect of suppressing the decrease in the content of methylmethionine sulfonium chloride (hereinafter sometimes referred to as "component (A)") and stabilizing it, thus completing the present invention.
すなわち、本発明は、次の成分（Ａ）及び（Ｂ）：
（Ａ）メチルメチオニンスルホニウムクロライド；
（Ｂ）コウボク及びその抽出物よりなる群から選ばれる１種以上；
を含有する組成物を提供するものである。
That is, the present invention relates to a composition comprising the following components (A) and (B):
(A) methylmethionine sulfonium chloride;
(B) one or more selected from the group consisting of magnolia bark and extracts thereof;
The present invention provides a composition comprising:
本発明によれば、メチルメチオニンスルホニウムクロライドの含量低下が抑制され安定性が改善された、品質安定性の良好な組成物を提供することができる。 According to the present invention, it is possible to provide a composition with good quality stability in which the decrease in the content of methylmethionine sulfonium chloride is suppressed and stability is improved.
＜成分（Ａ）＞
「メチルメチオニンスルホニウムクロライド」は、ビタミンＵとしても知られる成分である。本発明においては、ＭＭＳＣとして市販品を用いることができる。具体的な市販品としては例えば、Ｕビット「ハマリワイ」（米沢浜理薬品工業(株)製）等が挙げられる。
<Component (A)>
"Methyl methionine sulfonium chloride" is a component also known as vitamin U. In the present invention, commercially available products can be used as MMSC. Specific examples of commercially available products include U-bit "Hamari Y" (manufactured by Yonezawa Hamari Pharmaceutical Co., Ltd.).
本発明において、ＭＭＳＣの含有量は特に限定されないが、期待する薬効の観点から、組成物全質量に対して、０．０５～５０質量％含有するのが好ましく、０．１～１０質量％含有するのがより好ましく、１～７．５質量％含有するのが更に好ましく、２．５～５質量％含有するのが特に好ましい。 In the present invention, the amount of MMSC contained is not particularly limited, but from the viewpoint of the expected medicinal effect, it is preferable that the amount of MMSC contained is 0.05 to 50% by mass, more preferably 0.1 to 10% by mass, even more preferably 1 to 7.5% by mass, and particularly preferably 2.5 to 5% by mass, based on the total mass of the composition.
＜成分（Ｂ）＞
「コウボク」（厚朴）とは、第十七改正日本薬局方に記載のとおり、ホオノキ（Magnolia obovata Thunberg (Magnolia hypoleuca Siebold et Zuccarini), Magnolia officinalis Rehder et Wilson 又は Magnolia officinalis Rehder et Wilson var. biloba Rehder et Wilson (Magnoliaceae)）の樹皮を意味する。コウボクは必要に応じてその形態を調節することができ、小片、小塊に切断若しくは粉砕、又は粉末に粉砕することができる。また、組成物の製造時の取扱の便宜等を考慮して、コウボクに何らかの抽出処理を施したもの（以下、「コウボク抽出物」と称する。）を用いてもよい。
なお、上記「コウボク抽出物」には、抽出処理に加えて、加熱、乾燥、粉砕等の加工処理を施したものも包含される。具体的には、コウボクを必要に応じて適当な大きさとした後に、適当な抽出溶媒を加えて浸出した液や、当該浸出液を濃縮した液（軟エキス、チンキ等）、さらにこれらを乾燥させたもの（乾燥エキス等）なども本発明の「コウボク抽出物」に包含される。
本発明において、コウボク及びその抽出物よりなる群から選ばれる１種以上としては、コウボク乾燥エキスが好ましい。
<Component (B)>
"Magnolia obovata" (thick magnolia) means the bark of Magnolia obovata Thunberg (Magnolia hypoleuca Siebold et Zuccarini), Magnolia officinalis Rehder et Wilson or Magnolia officinalis Rehder et Wilson var. biloba Rehder et Wilson (Magnoliaceae)) as described in the 17th revised Japanese Pharmacopoeia. The form of the Magnolia obovata can be adjusted as necessary, and it can be cut or crushed into small pieces or lumps, or crushed into powder. In addition, in consideration of the convenience of handling during the production of the composition, a Magnolia obovata that has been subjected to some kind of extraction treatment (hereinafter referred to as "Magnolia obovata extract") may be used.
The above-mentioned "magnolia bark extract" also includes those that have been subjected to processing such as heating, drying, pulverization, etc., in addition to extraction. Specifically, the "magnolia bark extract" of the present invention includes a liquid obtained by cutting the magnolia bark into pieces of an appropriate size as necessary and then adding an appropriate extraction solvent to the resulting extract, a liquid obtained by concentrating the extract (soft extract, tincture, etc.), and further a liquid obtained by drying these (dried extract, etc.).
In the present invention, the one or more selected from the group consisting of Magnolia bark and extracts thereof is preferably Magnolia bark dried extract.
コウボク抽出物の製造方法は特に限定されず、例えば第十七改正日本薬局方 製剤総則の「エキス剤」、「浸剤・煎剤」、「チンキ剤」、「流エキス剤」の項の記載など、公知の植物抽出物の製造方法を参考にして製造できる。具体的には例えば、コウボクを必要に応じて切断、加熱、乾燥、粉砕等したうえ、適当な抽出溶媒を加え抽出を行うことで、製造することができる。得られた抽出物は、必要に応じさらに濃縮、乾燥等させてもよい。 The method for producing Magnolia bark extract is not particularly limited, and it can be produced by referring to known methods for producing plant extracts, such as those described in the General Provisions for Preparations of the 17th Revised Japanese Pharmacopoeia, under the headings "Extracts," "Infusions/Decoctions," "Tinctures," and "Liquid Extracts." Specifically, for example, Magnolia bark can be cut, heated, dried, crushed, etc. as necessary, and then extracted by adding an appropriate extraction solvent. The obtained extract may be further concentrated, dried, etc., as necessary.
上記抽出溶媒としては例えば、メタノール、エタノール、イソプロパノール、ｎ－ブタノール等の低級一価アルコール；エチレングリコール、プロピレングリコール、１，３－ブチレングリコール、グリセリン等の低級多価アルコール；ジエチルエーテル等のエーテル類；アセトン、エチルメチルケトン等のケトン類；酢酸エチル等のエステル類；アセトニトリル等のニトリル類；ペンタン、ヘキサン、シクロペンタン、シクロヘキサン等のアルカン類；ジクロロメタン、クロロホルム等のハロゲノアルカン類；ベンゼン、トルエン等の芳香族炭化水素；ジメチルホルムアミド等のアミド類；ジメチルスルホキシド等のスルホキシド類；水（熱水を含む）等が挙げられる。これらは各々単独で用いてもよいし、２種以上を組み合わせて用いてもよい。本発明においては、低級一価アルコール（より好適には炭素数１～６の低級一価アルコール）、水又はこれらの混液が好ましく、エタノール、水、又は水とエタノールの混液が特に好ましい。
抽出操作は特に限定されず、植物からの抽出操作に利用される公知の方法を採用することができ、具体的には例えば、抽出溶媒への浸漬（冷浸、温浸、パーコレーション等）、超臨界流体や亜臨界流体を用いた抽出などが挙げられる。なお、抽出効率を上げるため、撹拌や抽出溶媒中でホモジナイズしてもよい。
抽出温度は特に限定されず、使用する抽出溶媒、抽出操作等により異なるが、５℃程度から抽出溶媒の沸点以下の温度とするのが好ましい。
抽出時間は特に限定されず、使用する抽出溶媒、抽出操作等により異なるが、１時間～１４日間程度とするのが好ましい。
Examples of the extraction solvent include lower monohydric alcohols such as methanol, ethanol, isopropanol, and n-butanol; lower polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; ethers such as diethyl ether; ketones such as acetone and ethyl methyl ketone; esters such as ethyl acetate; nitriles such as acetonitrile; alkanes such as pentane, hexane, cyclopentane, and cyclohexane; halogenoalkanes such as dichloromethane and chloroform; aromatic hydrocarbons such as benzene and toluene; amides such as dimethylformamide; sulfoxides such as dimethyl sulfoxide; and water (including hot water). These may be used alone or in combination of two or more. In the present invention, lower monohydric alcohols (more preferably lower monohydric alcohols having 1 to 6 carbon atoms), water, or a mixture thereof is preferred, and ethanol, water, or a mixture of water and ethanol is particularly preferred.
The extraction procedure is not particularly limited, and any known method used for extraction from plants can be used, specifically, for example, immersion in an extraction solvent (cold immersion, hot immersion, percolation, etc.), extraction using a supercritical fluid or subcritical fluid, etc. In order to increase the extraction efficiency, stirring or homogenization in the extraction solvent may be performed.
The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction procedure, etc., but is preferably from about 5° C. to a temperature below the boiling point of the extraction solvent.
The extraction time is not particularly limited and varies depending on the extraction solvent used, the extraction procedure, etc., but is preferably about 1 hour to 14 days.
また、本発明において、コウボク及びその抽出物よりなる群から選ばれる１種以上としては、これらを成分として含む漢方処方を用いてもよい。このような漢方処方としては、具体的には例えば、半夏厚朴湯、厚朴生姜半夏人参甘草湯、香砂平胃散、柴朴湯、小承気湯、茯苓飲合半夏厚朴湯等が挙げられる。 In addition, in the present invention, one or more selected from the group consisting of Magnolia bark and its extracts may be used as a Kampo prescription containing these as ingredients. Specific examples of such Kampo prescriptions include Hange-Kouboku-Tang, Kouboku-Shoga-Hange-Ninjin-Kanzo-Tang, Kosha-Hei-San, Chai-Bo-Tang, Sho-Seiki-Tang, and Fu-Ryo-In-Go-Hange-Kouboku-Tang.
本発明において、コウボク及びその抽出物よりなる群から選ばれる１種以上としては、市販品を用いることができ、具体的な市販品としては例えば、コウボク乾燥エキス、コウボク乾燥エキス－Ｓ、コウボクエキス、コウボクエキス－Ａ、コウボク流エキス、（局）コウボク末（以上、日本粉末薬品（株）製）等が挙げられる。 In the present invention, one or more selected from the group consisting of Magnolia bark and extracts thereof may be commercially available products, and specific examples of commercially available products include Magnolia bark dry extract, Magnolia bark dry extract-S, Magnolia bark extract, Magnolia bark extract-A, Magnolia bark liquid extract, Magnolia bark powder (topical) (all manufactured by Nippon Powder Pharmaceutical Co., Ltd.), etc.
本発明において、コウボク及びその抽出物よりなる群から選ばれる１種以上の含有量は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、組成物全質量に対して、０．０１～６０質量％含有するのが好ましく、０．０５～５質量％含有するのがより好ましく、０．１～１質量％含有するのが特に好ましい。また、コウボク及びその抽出物よりなる群から選ばれる１種以上の含有量を原生薬量に換算した場合においては、ＭＭＳＣの含量低下の抑制の観点から、コウボク及びその抽出物よりなる群から選ばれる１種以上を組成物全質量に対して原生薬換算量で、０．１～８００質量％含有するのが好ましく、１～６００質量％含有するのがより好ましく、２～５０質量％含有するのが更に好ましく、３～７質量％含有するのが特に好ましい。 In the present invention, the content of one or more selected from the group consisting of Magnolia bark and its extracts is not particularly limited, but from the viewpoint of suppressing a decrease in the MMSC content, it is preferably 0.01 to 60% by mass, more preferably 0.05 to 5% by mass, and particularly preferably 0.1 to 1% by mass, based on the total mass of the composition. Furthermore, when the content of one or more selected from the group consisting of Magnolia bark and its extracts is converted into the amount of raw herbal medicine, from the viewpoint of suppressing a decrease in the MMSC content, it is preferably 0.1 to 800% by mass, more preferably 1 to 600% by mass, even more preferably 2 to 50% by mass, and particularly preferably 3 to 7% by mass, of one or more selected from the group consisting of Magnolia bark and its extracts, based on the total mass of the composition, based on the amount of raw herbal medicine.
また、ＭＭＳＣと、コウボク及びその抽出物よりなる群から選ばれる１種以上との含有質量比率は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、ＭＭＳＣを１質量部に対し、コウボク及びその抽出物よりなる群から選ばれる１種以上を０．００１～１０質量部含有するのが好ましく、０．００５～５質量部含有するのがより好ましく、０．０１～３質量部含有するのが更に好ましく、０．０５～２．５質量部含有するのが特に好ましい。さらに、コウボク及びその抽出物よりなる群から選ばれる１種以上の含有量を原生薬量に換算した場合においては、ＭＭＳＣの含量低下の抑制の観点から、ＭＭＳＣを１質量部に対し、コウボク及びその抽出物よりなる群から選ばれる１種以上を原生薬換算量で、０．０１～２０質量部含有するのが好ましく、０．１～１０質量部含有するのがより好ましく、０．５～５質量部含有するのが特に好ましい。 The mass ratio of MMSC to one or more selected from the group consisting of magnolia bark and its extracts is not particularly limited, but from the viewpoint of suppressing a decrease in the MMSC content, it is preferable that one or more selected from the group consisting of magnolia bark and its extracts is contained in an amount of 0.001 to 10 parts by mass, more preferably 0.005 to 5 parts by mass, even more preferably 0.01 to 3 parts by mass, and particularly preferably 0.05 to 2.5 parts by mass per part by mass of MMSC. Furthermore, when the content of one or more selected from the group consisting of magnolia bark and its extracts is converted into the amount of raw herbal medicine, from the viewpoint of suppressing a decrease in the MMSC content, it is preferable that one or more selected from the group consisting of magnolia bark and its extracts is contained in an amount of 0.01 to 20 parts by mass, more preferably 0.1 to 10 parts by mass, and particularly preferably 0.5 to 5 parts by mass per part by mass of MMSC, in terms of the amount of raw herbal medicine.
本発明の組成物においては、ＭＭＳＣの含量低下の抑制の観点から、ＭＭＳＣ並びにコウボク及びその抽出物よりなる群から選ばれる１種以上に加えて、さらに、任意にソヨウ及びその抽出物よりなる群から選ばれる１種以上（以下、「成分（Ｃ）」と称することもある。）、並びにデンプン類（以下、「成分（Ｄ）」と称することもある。）よりなる群から選ばれる１種以上を含有せしめてもよい。後記試験例に具体的に開示されているとおり、ＭＭＳＣと、コウボク及びその抽出物よりなる群から選ばれる１種以上とに加えて、さらにソヨウ及びその抽出物よりなる群から選ばれる１種以上や、デンプン類を共存せしめることにより、ＭＭＳＣの含量低下をより一層抑制できることが明らかとなった。 In the composition of the present invention, from the viewpoint of suppressing the decrease in the MMSC content, in addition to MMSC and one or more selected from the group consisting of Magnolia bark and its extracts, it may further contain one or more selected from the group consisting of Perilla herb and its extracts (hereinafter sometimes referred to as "component (C)"), and one or more selected from the group consisting of starches (hereinafter sometimes referred to as "component (D)"). As specifically disclosed in the test examples below, it has been revealed that the decrease in the MMSC content can be further suppressed by allowing the coexistence of MMSC, one or more selected from the group consisting of Magnolia bark and its extracts, and one or more selected from the group consisting of Perilla herb and its extracts, and starches.
＜成分（Ｃ）＞
本発明の組成物において任意に含有せしめられ得る「ソヨウ」（蘇葉）とは、第十六改正日本薬局方に記載のとおり、シソ（Perilla frutescens Britton var. acuta Kudo）又はチリメンジソ（Perilla frutescens Britton var. crispa Decaisne（Labiatae））の葉及び枝先を意味する。ソヨウは必要に応じてその形態を調節することができ、小片、小塊に切断若しくは粉砕、又は粉末に粉砕することができる。また、組成物の製造時の取扱の便宜等を考慮して、ソヨウに何らかの抽出処理を施したもの（以下、「ソヨウ抽出物」と称する。）を用いてもよい。
なお、上記「ソヨウ抽出物」には、抽出処理に加えて、加熱、乾燥、粉砕等の加工処理を施したものも包含される。具体的には、ソヨウを必要に応じて適当な大きさとした後に、適当な抽出溶媒を加えて浸出した液や、当該浸出液を濃縮した液（軟エキス、チンキ等）、さらにこれらを乾燥させたもの（乾燥エキス等）なども本発明の「ソヨウ抽出物」に包含される。
本発明において、ソヨウ及びその抽出物よりなる群から選ばれる１種以上としては、ソヨウ乾燥エキスが好ましい。
<Component (C)>
"Perilla frutescens" (Perilla frutescens Britton var. acuta Kudo) or chirimen shiso (Perilla frutescens Britton var. crispa Decaisne (Labiatae)) leaves and branch tips as described in the 16th Revised Japanese Pharmacopoeia. The form of Perilla frutescens can be adjusted as necessary, and it can be cut or crushed into small pieces or small chunks, or crushed into powder. In addition, Perilla frutescens that has been subjected to some kind of extraction treatment (hereinafter referred to as "Perilla frutescens extract") may be used in consideration of the convenience of handling during the production of the composition.
The above-mentioned "Perilla extract" also includes those that have been subjected to processing such as heating, drying, crushing, etc., in addition to extraction. Specifically, the "Perilla extract" of the present invention includes a liquid obtained by cutting Perilla into pieces of an appropriate size as necessary and then adding an appropriate extraction solvent to the resulting extract, a liquid obtained by concentrating the extract (soft extract, tincture, etc.), and further a liquid obtained by drying these (dried extract, etc.).
In the present invention, the one or more selected from the group consisting of Perilla japonica and extracts thereof is preferably a Perilla japonica dry extract.
ソヨウ抽出物の製造方法は特に限定されず、例えば、上記したコウボク抽出物の製造方法と同様の方法により製造できる。 The method for producing the Perilla extract is not particularly limited, and it can be produced, for example, by a method similar to the method for producing the Magnolia extract described above.
また、本発明において、ソヨウ及びその抽出物よりなる群から選ばれる１種以上としては、これらを成分として含む漢方処方を用いてもよい。このような漢方処方としては、具体的には例えば、香蘇散（コウソサン）、蘇子降気湯（ソシコウキトウ）、かっ香正気散（カッコウショウキサン）、茯苓飲合半夏厚朴湯（ブクリョウインゴウハンゲコウボクトウ）、半夏厚朴湯（ハンゲコウボクトウ）等が挙げられる。 In the present invention, the one or more selected from the group consisting of Perilla japonica and its extracts may be a herbal prescription containing these as an ingredient. Specific examples of such herbal prescriptions include Kososan, Soshi Koukito, Kakkoshoukisan, Bukryoingou Hange Koubokuto, Hange Koubokuto, etc.
本発明において、ソヨウ及びその抽出物よりなる群から選ばれる１種以上としては、市販品を用いることができ、具体的な市販品としては例えば、ソヨウ流エキス、蘇葉乾燥エキス（以上、日本粉末薬品(株)製）等が挙げられる。 In the present invention, one or more selected from the group consisting of Perilla japonica and its extracts may be commercially available products. Specific examples of commercially available products include Perilla japonica liquid extract and Perilla japonica leaf dried extract (both manufactured by Nippon Powder Pharmaceutical Co., Ltd.).
本発明において、ソヨウ及びその抽出物よりなる群から選ばれる１種以上の含有量は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、組成物全質量に対して、０．０１～５０質量％含有するのが好ましく、０．０５～５質量％含有するのがより好ましく、０．１～３質量％含有するのが特に好ましい。また、ソヨウ及びその抽出物よりなる群から選ばれる１種以上の含有量を原生薬量に換算した場合においては、ＭＭＳＣの含量低下の抑制作用の観点から、ソヨウ及びその抽出物よりなる群から選ばれる１種以上を組成物全質量に対して原生薬換算量で、０．１～８００質量％含有するのが好ましく、１～６００質量％含有するのがより好ましく、２～５０質量％含有するのが更に好ましく、３～７質量％含有するのが特に好ましい。 In the present invention, the content of one or more selected from the group consisting of Perilla herb and its extracts is not particularly limited, but from the viewpoint of suppressing the decrease in the MMSC content, it is preferably 0.01 to 50% by mass, more preferably 0.05 to 5% by mass, and particularly preferably 0.1 to 3% by mass, based on the total mass of the composition. In addition, when the content of one or more selected from the group consisting of Perilla herb and its extracts is converted into the amount of raw herb, from the viewpoint of the suppression effect of the decrease in the MMSC content, it is preferably 0.1 to 800% by mass, more preferably 1 to 600% by mass, even more preferably 2 to 50% by mass, and particularly preferably 3 to 7% by mass, of one or more selected from the group consisting of Perilla herb and its extracts, based on the total mass of the composition, based on the amount of raw herb.
また、ＭＭＳＣと、ソヨウ及びその抽出物よりなる群から選ばれる１種以上との含有質量比率は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、ＭＭＳＣを１質量部に対し、ソヨウ及びその抽出物よりなる群から選ばれる１種以上を０．００１～５０質量部含有するのが好ましく、０．０１～５質量部含有するのがより好ましく、０．０５～１質量部含有するのが特に好ましい。また、ソヨウ及びその抽出物よりなる群から選ばれる１種以上の含有量を原生薬量に換算した場合においては、ＭＭＳＣの含量低下の抑制の観点から、ＭＭＳＣを１質量部に対し、ソヨウ及びその抽出物よりなる群から選ばれる１種以上を原生薬換算量で、０．１～１０質量部含有するのが好ましく、０．０１～１５質量部含有するのがより好ましく、０．５～５質量部含有するのが特に好ましい。 The mass ratio of MMSC to one or more selected from the group consisting of Perilla herb and its extracts is not particularly limited, but from the viewpoint of suppressing the decrease in the MMSC content, it is preferable that 0.001 to 50 parts by mass, more preferably 0.01 to 5 parts by mass, and particularly preferably 0.05 to 1 part by mass of one or more selected from the group consisting of Perilla herb and its extracts are contained per part by mass of MMSC in an amount equivalent to the raw herb, preferably 0.1 to 10 parts by mass, more preferably 0.01 to 15 parts by mass, and particularly preferably 0.5 to 5 parts by mass of one or more selected from the group consisting of Perilla herb and its extracts, in terms of the amount of raw herb, from the viewpoint of suppressing the decrease in the MMSC content.
また、コウボク及びその抽出物よりなる群から選ばれる１種以上と、ソヨウ及びその抽出物よりなる群から選ばれる１種以上との含有質量比率は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、コウボク及びその抽出物よりなる群から選ばれる１種以上を１質量部に対し、ソヨウ及びその抽出物よりなる群から選ばれる１種以上を０．０１～１０質量部含有するのが好ましく、０．０５～５質量部含有するのがより好ましく、０．１～２質量部含有するのが特に好ましい。さらに、両成分の含有量を原生薬量に換算した場合においては、ＭＭＳＣの含量低下の抑制の観点から、コウボク及びその抽出物よりなる群から選ばれる１種以上を原生薬換算量で１質量部に対し、ソヨウ及びその抽出物よりなる群から選ばれる１種以上を原生薬換算量で、０．０１～１０質量部含有するのが好ましく、０．１～５質量部含有するのがより好ましく、０．５～２質量部含有するのが特に好ましい。 The mass ratio of one or more selected from the group consisting of Magnolia bark and its extracts to one or more selected from the group consisting of Perilla herb and its extracts is not particularly limited, but from the viewpoint of suppressing the decrease in the MMSC content, it is preferable to contain 0.01 to 10 parts by mass, more preferably 0.05 to 5 parts by mass, and particularly preferably 0.1 to 2 parts by mass of one or more selected from the group consisting of Perilla herb and its extracts per part by mass of Magnolia bark and its extracts in terms of suppressing the decrease in the MMSC content. Furthermore, when the contents of both components are converted into the amount of raw herbal medicine, it is preferable to contain 0.01 to 10 parts by mass, more preferably 0.1 to 5 parts by mass, and particularly preferably 0.5 to 2 parts by mass of one or more selected from the group consisting of Perilla herb and its extracts per part by mass of Magnolia bark and its extracts in terms of raw herbal medicine, from the viewpoint of suppressing the decrease in the MMSC content.
＜成分（Ｄ）＞
本発明の組成物において任意に含有せしめられ得る「デンプン類」とは、デンプンそのもの、デンプンのヒドロキシ基の全部又は一部がエーテル結合を形成したもの、及びそれらの誘導体、並びにそれらの塩よりなる群から選ばれる１種以上を意味する。なお、デンプン類には、糊化、老化等の処理がなされたものも含まれる。また、上記誘導体には、デンプンやそのエーテル化物に、必要に応じてエステル化、架橋形成、加水分解等、更なる修飾がなされたものも包含される。ここで塩としては特に限定されず、具体的には例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩；カルシウム塩、マグネシウム塩等の第２族元素との塩等が挙げられる。
こうしたデンプン類としては、具体的には例えば、アルファ化デンプン、コムギデンプン、コメデンプン、トウモロコシデンプン、バレイショデンプン、部分アルファ化デンプン、小麦粉、米粉、半消化デンプン等のデンプン又はその塩；ヒドロキシプロピルスターチ等の、デンプンのヒドロキシアルキルエーテル又はその塩；カルボキシメチルスターチナトリウム等の、デンプンのカルボキシアルキルエーテル又はその塩等が挙げられ、これらのうち１種を単独で用いても２種以上を組み合わせて用いてもよい。なお、当該デンプン類におけるアルキル基としては特に限定されないが、炭素数１～６の直鎖状又は分岐鎖状のアルキル基が好ましい。
<Component (D)>
The "starches" that may be optionally contained in the composition of the present invention refer to one or more selected from the group consisting of starch itself, starch in which all or part of the hydroxyl groups of starch form ether bonds, and derivatives thereof, as well as salts thereof. The starches also include those that have been subjected to treatments such as gelatinization and aging. The derivatives also include those in which starch or its etherified products have been further modified, as necessary, by esterification, crosslinking, hydrolysis, etc. The salts are not particularly limited, and specific examples thereof include alkali metal salts such as sodium salts and potassium salts; salts with Group 2 elements such as calcium salts and magnesium salts; and the like.
Specific examples of such starches include starches or salts thereof such as pregelatinized starch, wheat starch, rice starch, corn starch, potato starch, partially pregelatinized starch, wheat flour, rice flour, and semi-digested starch; hydroxyalkyl ethers of starch or salts thereof such as hydroxypropyl starch; and carboxyalkyl ethers of starch or salts thereof such as sodium carboxymethyl starch, among which one may be used alone or two or more may be used in combination. The alkyl group in the starches is not particularly limited, but a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms is preferred.
デンプン類としては、ＭＭＳＣの含量低下の抑制の観点から、デンプン、デンプンのヒドロキシアルキルエーテル及びデンプンのカルボキシアルキルエーテル並びにそれらの塩よりなる群から選ばれる１種以上が好ましく、デンプン、デンプンのヒドロキシＣ１－Ｃ６アルキルエーテル及びデンプンのカルボキシＣ１－Ｃ６アルキルエーテル並びにそれらの塩よりなる群から選ばれる１種以上がより好ましく、デンプン、ヒドロキシプロピルスターチ及びカルボキシメチルスターチ並びにそれらの塩よりなる群から選ばれる１種以上がさらに好ましく、デンプン及びカルボキシメチルスターチナトリウムよりなる群から選ばれる１種以上がさらにより好ましく、トウモロコシデンプンが特に好ましい。
なお、これらのデンプン類はいずれも公知の成分であり、公知の方法により製造しても良く、また、市販品を使用しても良い。なお、こうした市販品としては例えば、ＬＹＣＡＴＡＢ ＰＧＳ（ロケットジャパン（株））、ＧＬＹＣＯＬＹＳ（ロケットジャパン（株））、デンプン（溶性）（キシダ化学（株））、トウモロコシデンプン（三栄源エフ・エフ・アイ（株））、バレイショデンプン（純正化学（株））、ＨＰＳ－１０１（フロイント産業（株））、ＬＹＣＡＴＡＢＣ（ロケットジャパン（株））等が挙げられる。
As the starches, from the viewpoint of suppressing a decrease in the MMSC content, one or more selected from the group consisting of starch, hydroxyalkyl ether of starch, carboxyalkyl ether of starch, and salts thereof are preferred, one or more selected from the group consisting of starch, hydroxy C1-C6 alkyl ether of starch, carboxy C1-C6 alkyl ether of starch, and salts thereof are more preferred, one or more selected from the group consisting of starch, hydroxypropyl starch, carboxymethyl starch, and salts thereof are even more preferred, one or more selected from the group consisting of starch and sodium carboxymethyl starch are even more preferred, and corn starch is particularly preferred.
These starches are all known components and may be produced by known methods, or commercially available products may be used. Examples of such commercially available products include LYCATAB PGS (Rocket Japan Co., Ltd.), GLYCOLYS (Rocket Japan Co., Ltd.), starch (soluble) (Kishida Chemical Co., Ltd.), corn starch (Sanei Gen F.F.I. Co., Ltd.), potato starch (Junsei Chemical Co., Ltd.), HPS-101 (Freund Corporation), and LYCATABC (Rocket Japan Co., Ltd.).
本発明において、デンプン類の含有量は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、組成物全質量に対して、０．０１～４０質量％含有するのが好ましく、０．０５～２０質量％含有するのがより好ましく、０．１～１０質量％含有するのが特に好ましい。 In the present invention, the content of starches is not particularly limited, but from the viewpoint of suppressing a decrease in the MMSC content, it is preferable that the content be 0.01 to 40% by mass, more preferably 0.05 to 20% by mass, and particularly preferably 0.1 to 10% by mass, based on the total mass of the composition.
また、ＭＭＳＣと、デンプン類との含有質量比率は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、ＭＭＳＣを１質量部に対し、デンプン類を０．０１～１０質量部含有するのが好ましく、０．１～５質量部含有するのがより好ましく、０．５～３質量部含有するのが特に好ましい。
また、コウボク及びその抽出物よりなる群から選ばれる１種以上と、デンプン類との含有質量比率は特に限定されないが、ＭＭＳＣの含量低下の抑制の観点から、コウボク及びその抽出物よりなる群から選ばれる１種以上を１質量部に対し、デンプン類を１～３０質量部含有するのが好ましく、３～２０質量部含有するのがより好ましく、５～１５質量部含有するのが特に好ましい。さらに、コウボク及びその抽出物よりなる群から選ばれる１種以上の含有量を原生薬量に換算した場合においては、ＭＭＳＣの含量低下の抑制の観点から、コウボク及びその抽出物よりなる群から選ばれる１種以上を原生薬換算量で１質量部に対し、デンプン類を０．０１～１０質量部含有するのが好ましく、０．０５～５質量部含有するのがより好ましく、０．１～１質量部含有するのが特に好ましい。
Furthermore, the mass ratio of MMSC to starches is not particularly limited, but from the viewpoint of suppressing a decrease in the MMSC content, it is preferable to contain 0.01 to 10 parts by mass of starches per 1 part by mass of MMSC, more preferably 0.1 to 5 parts by mass, and particularly preferably 0.5 to 3 parts by mass.
In addition, the mass ratio of the one or more selected from the group consisting of Magnolia bark and its extracts to the starches is not particularly limited, but from the viewpoint of suppressing a decrease in the MMSC content, the starches are preferably contained in an amount of 1 to 30 parts by mass, more preferably 3 to 20 parts by mass, and particularly preferably 5 to 15 parts by mass per part by mass of the one or more selected from the group consisting of Magnolia bark and its extracts. Furthermore, when the content of the one or more selected from the group consisting of Magnolia bark and its extracts is converted into the amount of raw herbal medicine, from the viewpoint of suppressing a decrease in the MMSC content, the starches are preferably contained in an amount of 0.01 to 10 parts by mass, more preferably 0.05 to 5 parts by mass, and particularly preferably 0.1 to 1 part by mass per part by mass of the one or more selected from the group consisting of Magnolia bark and its extracts in terms of raw herbal medicine.
本発明において、「組成物」は、固形状、半固形状、液状のいずれの形状であってもよく、その利用目的に応じて医薬品、医薬部外品、化粧品、食品等において通常利用される形状とすることができる。具体的には例えば、錠剤（口腔内崩壊錠、チュアブル錠、発泡錠、分散錠、溶解錠、口腔用錠剤（トローチ剤、舌下錠、バッカル錠、付着錠、ガム剤を含む。）を含む。）、カプセル剤、顆粒剤（発泡顆粒剤を含む。）、散剤などの固形状製剤；経口液剤（エリキシル剤、懸濁剤、乳剤、リモナーデ剤を含む。）、シロップ剤、口腔用液剤などの液状製剤；経口ゼリー剤、口腔用半固形剤などの半固形状製剤などの、第十七改正日本薬局方 製剤総則等に記載の剤形とすることができる。
本発明においては、ＭＭＳＣの含量低下の抑制の観点から、固形状の組成物であるのが好ましく、錠剤、カプセル剤、顆粒剤及び散剤よりなる群から選ばれる剤形であるのがより好ましく、錠剤及び顆粒剤よりなる群から選ばれる剤形であるのが特に好ましい。
In the present invention, the "composition" may be in any form of solid, semi-solid, or liquid, and may be in a form that is generally used in medicines, quasi-drugs, cosmetics, foods, etc., depending on the intended use. Specifically, the composition may be in a dosage form described in the General Provisions for Preparations of the 17th Revised Japanese Pharmacopoeia, etc., such as solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, oral tablets (including lozenges, sublingual tablets, buccal tablets, adhesive tablets, and gums)), capsules, granules (including effervescent granules), and powders; liquid preparations such as oral liquids (including elixirs, suspensions, emulsions, and lemonades), syrups, and oral liquids; and semi-solid preparations such as oral jellies and oral semi-solids.
In the present invention, from the viewpoint of suppressing a decrease in the MMSC content, a solid composition is preferable, a dosage form selected from the group consisting of tablets, capsules, granules and powders is more preferable, and a dosage form selected from the group consisting of tablets and granules is particularly preferable.
本発明の組成物においては、上記した成分の他に、上記した形状・剤形に応じて医薬品分野、医薬部外品分野、化粧品分野、食品分野等において公知の方法、例えば第十七改正日本薬局方 製剤総則等に記載の方法に従って製造することができる。
本発明の組成物は、上記した成分のほかに、医薬品分野、医薬部外品分野、化粧品分野、食品分野等において使用される担体（賦形剤、結合剤、崩壊剤、滑沢剤、着色剤、矯味剤、コーティング剤等）の１種又は２種以上を配合してもよい。
賦形剤としては、乳糖、結晶セルロース、ショ糖、マンニトール、軽質無水ケイ酸等が挙げられる。結合剤としては、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルセルロース、ゼラチン、ポリビニルピロリドン、ポリビニルアルコール、プルラン等が挙げられる。崩壊剤としては、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、クロスポビドン、低置換度ヒドロキシプロピルセルロース等が挙げられる。滑沢剤としては、ステアリン酸マグネシウム、タルク等が挙げられる。着色剤としては、タール色素、三二酸化鉄等が挙げられる。矯味剤としては、ステビア、アスパルテーム等が挙げられる。コーティング剤としては、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース、メタアクリル酸コポリマーＳ、メタアクリル酸コポリマーＬ、メタアクリル酸コポリマーＬＤ、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート等のフィルム形成高分子が挙げられる。なお、フィルム形成させる際に、クエン酸トリエチル、トリアセチン、ポリエチレングリコール等の可塑剤、タルク、酸化チタン、黄色三二酸化鉄、三二酸化鉄、法定色素、軽質無水ケイ酸、含水二酸化ケイ素等の紛体を配合することもできる。本発明においては、これらの１種又は２種以上を適宜組み合わせて配合することができる。
In addition to the above-mentioned components, the composition of the present invention can be produced according to a method known in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, and the like, depending on the above-mentioned shape and dosage form, for example, according to the method described in the General Provisions for Preparations of the Japanese Pharmacopoeia, 17th Edition.
In addition to the above-mentioned components, the composition of the present invention may contain one or more carriers (such as excipients, binders, disintegrants, lubricants, colorants, flavoring agents, coating agents, etc.) used in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, etc.
Examples of the excipient include lactose, crystalline cellulose, sucrose, mannitol, and light anhydrous silicic acid. Examples of the binder include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, and pullulan. Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, and low-substituted hydroxypropylcellulose. Examples of the lubricant include magnesium stearate and talc. Examples of the colorant include tar dyes and ferric oxide. Examples of the flavoring agent include stevia and aspartame. Examples of the coating agent include film-forming polymers such as carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, and hydroxypropylmethylcellulose acetate succinate. When forming the film, it is also possible to blend in a plasticizer such as triethyl citrate, triacetin, polyethylene glycol, etc., or a powder such as talc, titanium oxide, yellow ferric oxide, ferric oxide, legally designated dyes, light anhydrous silicic acid, hydrous silicon dioxide, etc. In the present invention, one or more of these may be blended in appropriate combination.
また、本発明の組成物には、上記した成分の他に、他の薬効成分を配合してもよい。このような薬効成分は特に限定されず、組成物を適用する疾患・症状等に応じて適宜検討して選択すればよいが、例えば、局所麻酔剤、消化剤（利胆剤）、消化酵素、胃粘膜修復剤（粘膜保護成分）、生薬成分、制酸剤等が挙げられ、これらを単独で、又は２種以上を組み合わせて配合できる。 In addition to the above-mentioned components, the composition of the present invention may contain other medicinal ingredients. Such medicinal ingredients are not particularly limited and may be selected appropriately depending on the disease or symptoms to which the composition is applied. Examples of such ingredients include local anesthetics, digestive agents (cholagogues), digestive enzymes, gastric mucosa repair agents (mucosa protective ingredients), herbal ingredients, and antacids, which may be used alone or in combination of two or more.
局所麻酔剤としては、アミノ安息香酸エチル、オキセサゼイン等が挙げられる。消化剤（利胆剤）としては、ウルソデオキシコール酸、動物胆（熊胆、牛胆）等が挙げられる。消化酵素としては、でんぷん消化酵素（ビオジアスターゼ、タカジアスターゼ）、脂肪消化酵素（リパーゼ）等が挙げられる。胃粘膜修復剤（粘膜保護成分）としては、銅クロロフィンナトリウム、銅クロロフィンカリウム、アルジオキサ、スクラルファート、塩酸セトラキサート、ソファルコン、ゲファルナート、マレイン酸トリメブチン、アズレンスルホン酸ナトリウム等が挙げられる。生薬成分としては、アセンヤク、アニス実、アロエ、ウイキョウ、ウコン、ウバイ、ウヤク、エンゴサク、延命草、オウゴン、オウバク、オウレン、加工大蒜、ガジュツ、カッコウ、カラムス根、カンキョウ、カンゾウ、キジツ、クジン、ケイヒ、ケツメイシ、ゲンチアナ、ゲンノショウコ、コウジン、ゴシュユ、胡椒、五倍子、コロンボ、コンズランゴ、サンザシ、サンショウ、山奈、シソシ、シャクヤク、シュクシャ、ショウキョウ、ショウズク、青皮、赤芽柏、石菖根、センタウリウム草、ソウジュツ、大茴香、ダイオウ、チクセツニンジン、チョウジ、チンピ、トウガラシ、トウヒ、ニガキ、ニクズク、ニンジン、ハッカ、セイヨウハッカ、ヒハツ、ビャクジュツ、ホップ、ホミカ、睡菜葉、ヤクチ、ヨウバイヒ、リュウタンおよびリョウキョウ等の生薬やその抽出物が挙げられる。制酸剤としては、オメプラゾール、ランソプラゾール、ラベプラゾールナトリウム等のプロトンポンプ阻害薬；シメチジン、塩酸ラニチジン、及びファモチジン等のＨ２受容体拮抗薬；乾燥水酸化アルミニウムゲル、ケイ酸アルミン酸マグネシウム、メタケイ酸アルミン酸マグネシウム、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、水酸化アルミナマグネシウム、水酸化アルミニウムゲル、水酸化アルミニウム・炭酸水素ナトリウム共沈生成物、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸マグネシウム・炭酸カルシウム共沈生成物、水酸化マグネシウム、炭酸水素ナトリウム、炭酸マグネシウム、沈降炭酸カルシウム、メタケイ酸アルミン酸マグネシウム、無水リン酸水素カルシウム、リン酸水素カルシウム等の無機塩類；烏賊骨、石決明、ボレイ、アミノ酢酸、ジヒドロキシアルミニウムアミノアセテート等が挙げられる。本発明においては、これらの１種又は２種以上を適宜組み合わせて配合することができる。 Local anesthetics include ethyl aminobenzoate, oxethazaine, etc. Digestive agents (cholagogues) include ursodeoxycholic acid, animal bile (bear bile, ox bile), etc. Digestive enzymes include starch digestive enzymes (biodiastase, takadiastase), fat digestive enzymes (lipase), etc. Gastric mucosa repair agents (mucosa protective components) include copper chlorophine sodium, copper chlorophine potassium, aldioxa, sucralfate, cetraxate hydrochloride, sofalcone, gefarnate, trimebutine maleate, sodium azulene sulfonate, etc. Herbal ingredients include acacia, aniseed, aloe, fennel, turmeric, Ubai, Uyaku, Corydalis rotundifolia, Enmeisou, Scutellaria Root, Phellodendron Bark, Coptis Rhizome, processed garlic, zedoary, cuckoo pea, calamus root, kankyo, licorice, pheasant, solanum rhizome, cinnamon bark, Cassia japonica, gentian, geranium herb, red ginseng, Chinese pepper, Chinese pepper, peppercorn, chinese pepper, chinese pepper, chinese pepper, Chinese pepper, Chinese quince, Chinese quince, Chinese quince, Chinese gallnut, Colombo, condurago, hawthorn, Japanese pepper, wild mustard, perilla, Examples of herbal medicines and extracts thereof include peony root, Chinese peony, ginger, cardamom, green bark, red cedar, acorus gramineus, centaurium grass, atractylodes rhizome, anemone, rhubarb, ginseng, clove, tangerine, chili pepper, spruce, bitter melon, nutmeg, carrot, mint, peppermint, long pepper, Atractylodes rhizome, hops, vomica, night cabbage leaf, yakuchi, morning glory, scutellaria, and rhubarb, etc. Examples of antacids include proton pump inhibitors such as omeprazole, lansoprazole, and sodium rabeprazole; H2 receptor antagonists such as cimetidine, ranitidine hydrochloride, and famotidine; inorganic salts such as dried aluminum hydroxide gel, magnesium aluminosilicate, magnesium aluminometasilicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide/sodium bicarbonate co-precipitation product, aluminum hydroxide/magnesium carbonate mixed dry gel, aluminum hydroxide/magnesium carbonate/calcium carbonate co-precipitation product, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, and calcium hydrogen phosphate; squid bone, stone jelly, borae, aminoacetic acid, and dihydroxyaluminum aminoacetate. In the present invention, one or more of these can be appropriately combined and formulated.
本発明の組成物は、医薬品、医薬部外品、化粧品、食品等として利用でき、その利用目的は特に限定されないが、消化管粘膜保護作用を有するＭＭＳＣを含有することから、好適には医薬として、より好適には胃潰瘍、十二指腸潰瘍、胃炎等の自覚症状及び他覚所見の改善や慢性肝疾患における肝機能の改善等のための医薬として用いることができる。また、胃腸薬として、より具体的には、胃部不快感、胃弱、もたれ、胃痛、食べ過ぎ、飲み過ぎ、胸やけ、はきけ（むかつき、胃のむかつき、二日酔・悪酔のむかつき、嘔気、悪心）、嘔吐、食欲不振、消化不良、胃酸過多、げっぷ、胸つかえ、消化促進、胃部・腹部膨満感、胃重よりなる群から選ばれる１種以上を効能・効果とする胃腸薬として好適に用いることができる。 The composition of the present invention can be used as a medicine, quasi-drug, cosmetic, food, etc., and the purpose of use is not particularly limited. However, since it contains MMSCs that have a gastrointestinal mucosa protecting effect, it can be preferably used as a medicine, more preferably as a medicine for improving subjective symptoms and objective findings of gastric ulcer, duodenal ulcer, gastritis, etc., and improving liver function in chronic liver disease. In addition, it can be preferably used as a gastrointestinal drug, more specifically, as a gastrointestinal drug with one or more efficacy/effects selected from the group consisting of stomach discomfort, weak stomach, heavy feeling, stomach pain, overeating, overdrinking, heartburn, nausea (retching, stomach retching, hangover/bad hangover retching, nausea, nausea), vomiting, loss of appetite, indigestion, hyperacidity, belching, chest tightness, digestion promotion, stomach/abdominal bloating, and stomach heaviness.
本発明の組成物の投与方法としては特に制限されず、経口投与及び非経口投与が挙げられ、組成物の利用目的等に応じて適宜選択することができるが、ＭＭＳＣの有する消化管粘膜保護作用の観点から、経口投与が好ましい。また、組成物の用法や用量は特に制限されず、組成物の利用目的や投与方法、組成物の剤形等に応じて適宜選択・決定すればよい。 The method of administration of the composition of the present invention is not particularly limited, and includes oral administration and parenteral administration, which can be appropriately selected depending on the intended use of the composition, etc., but oral administration is preferred from the viewpoint of the gastrointestinal mucosa protecting effect of MMSCs. In addition, the method of use and dosage of the composition are not particularly limited, and may be appropriately selected and determined depending on the intended use of the composition, the method of administration, the dosage form of the composition, etc.
また、本発明は、次の成分（Ａ）：
（Ａ）メチルメチオニンスルホニウムクロライド；
と、次の成分（Ｂ）：
（Ｂ）コウボク及びその抽出物よりなる群から選ばれる１種以上；
とを、同一の組成物中に含有せしめる工程を含む、組成物中のメチルメチオニンスルホニウムクロライドの安定化方法（好適には、組成物中のメチルメチオニンスルホニウムクロライドの含量低下を抑制する方法）にも関する。
斯かる態様の発明において、成分（Ａ）を含有せしめる工程、成分（Ｂ）を含有せしめる工程の順序は特に限定されず、成分（Ａ）及び（Ｂ）を含有する組成物が直接的又は間接的に作出されればよい。
なお、斯かる態様の発明において、各種文言の意義、各成分の配合量等は全て上記した「組成物」について説明したのと同様である。
The present invention also relates to the following component (A):
(A) methylmethionine sulfonium chloride;
and the following component (B):
(B) one or more selected from the group consisting of magnolia bark and extracts thereof;
and a method for stabilizing methylmethionine sulfonium chloride in a composition (preferably a method for suppressing a decrease in the content of methylmethionine sulfonium chloride in a composition), the method comprising the step of incorporating both in the same composition.
In the invention of such an embodiment, the order of the step of incorporating component (A) and the step of incorporating component (B) is not particularly limited, as long as a composition containing components (A) and (B) is produced directly or indirectly.
In the invention of this embodiment, the meanings of various terms, the amounts of each component, etc. are all the same as those explained for the "composition" above.
本明細書は、これらに何ら限定されるものではないが、例えば以下の実施態様を開示する。
［１Ａ］ 次の成分（Ａ）及び（Ｂ）：
（Ａ）メチルメチオニンスルホニウムクロライド；
（Ｂ）コウボク及びその抽出物よりなる群から選ばれる１種以上；
を含有する、組成物。
［２Ａ］ コウボクの抽出物が、水、低級一価アルコール及びこれらの混液よりなる群から選ばれる溶媒を抽出溶媒としたものである、［１Ａ］に記載の組成物。
［３Ａ］ さらに、次の成分（Ｃ）及び（Ｄ）よりなる群から選ばれる１種以上；
（Ｃ）ソヨウ及びその抽出物よりなる群から選ばれる１種以上；
（Ｄ）デンプン類；
を含有する、［１Ａ］又は［２Ａ］に記載の組成物。
［４Ａ］ ソヨウの抽出物が、水、低級一価アルコール及びこれらの混液よりなる群から選ばれる溶媒を抽出溶媒としたものである、［３Ａ］に記載の組成物。
［５Ａ］ デンプン類が、デンプン、デンプンのヒドロキシＣ１－Ｃ６アルキルエーテル及びデンプンのカルボキシＣ１－Ｃ６アルキルエーテル並びにそれらの塩よりなる群から選ばれる１種以上である、［３Ａ］又は［４Ａ］に記載の組成物。
［６Ａ］ デンプン類が、デンプン、ヒドロキシプロピルスターチ及びカルボキシメチルスターチ並びにそれらの塩よりなる群から選ばれる１種以上である、［３Ａ］～［５Ａ］のいずれかに記載の組成物。
［７Ａ］ 固形状の組成物である、［１Ａ］～［６Ａ］のいずれかに記載の組成物。
［８Ａ］ 錠剤、カプセル剤、顆粒剤及び散剤よりなる群から選ばれる剤形である、［１Ａ］～［７Ａ］のいずれかに記載の組成物。
［９Ａ］ 胃腸薬である、［１Ａ］～［８Ａ］のいずれかに記載の組成物。
The present specification discloses, for example, the following embodiments, but is in no way limited thereto.
[1A] The following components (A) and (B):
(A) methylmethionine sulfonium chloride;
(B) one or more selected from the group consisting of magnolia bark and extracts thereof;
A composition comprising:
[2A] The composition according to [1A], wherein the extract of Magnolia bark is extracted using a solvent selected from the group consisting of water, a lower monohydric alcohol, and a mixture thereof as an extraction solvent.
[3A] Furthermore, one or more selected from the group consisting of the following components (C) and (D);
(C) one or more selected from the group consisting of Perilla japonica and extracts thereof;
(D) starches;
The composition according to [1A] or [2A],
[4A] The composition according to [3A], wherein the extract of Perilla japonica is obtained by using a solvent selected from the group consisting of water, a lower monohydric alcohol, and a mixture thereof as an extraction solvent.
[5A] The composition according to [3A] or [4A], wherein the starches are one or more selected from the group consisting of starch, hydroxy C1-C6 alkyl ether of starch, carboxy C1-C6 alkyl ether of starch, and salts thereof.
[6A] The composition according to any one of [3A] to [5A], wherein the starches are one or more selected from the group consisting of starch, hydroxypropyl starch, carboxymethyl starch, and salts thereof.
[7A] The composition according to any one of [1A] to [6A], which is a solid composition.
[8A] The composition according to any one of [1A] to [7A], which is in a dosage form selected from the group consisting of tablets, capsules, granules, and powders.
[9A] The composition according to any one of [1A] to [8A], which is a gastrointestinal drug.
［１Ｂ］ 次の成分（Ａ）：
（Ａ）メチルメチオニンスルホニウムクロライド；
と、次の成分（Ｂ）：
（Ｂ）コウボク及びその抽出物よりなる群から選ばれる１種以上；
とを、同一の組成物中に含有せしめる工程を含む、組成物中のメチルメチオニンスルホニウムクロライドの安定化方法。
［２Ｂ］ コウボクの抽出物が、水、低級一価アルコール及びこれらの混液よりなる群から選ばれる溶媒を抽出溶媒としたものである、［１Ｂ］に記載の方法。
［３Ｂ］ さらに、次の成分（Ｃ）及び（Ｄ）よりなる群から選ばれる１種以上；
（Ｃ）ソヨウ及びその抽出物よりなる群から選ばれる１種以上；
（Ｄ）デンプン類；
を同一の組成物中に含有せしめる、［１Ｂ］又は［２Ｂ］に記載の方法。
［４Ｂ］ ソヨウの抽出物が、水、低級一価アルコール及びこれらの混液よりなる群から選ばれる溶媒を抽出溶媒としたものである、［３Ｂ］に記載の方法。
［５Ｂ］ デンプン類が、デンプン、デンプンのヒドロキシＣ１－Ｃ６アルキルエーテル及びデンプンのカルボキシＣ１－Ｃ６アルキルエーテル並びにそれらの塩よりなる群から選ばれる１種以上である、［３Ｂ］又は［４Ｂ］に記載の方法。
［６Ｂ］ デンプン類が、デンプン、ヒドロキシプロピルスターチ及びカルボキシメチルスターチ並びにそれらの塩よりなる群から選ばれる１種以上である、［３Ｂ］～［５Ｂ］のいずれかに記載の方法。
［７Ｂ］ 組成物が、固形状の組成物である、［１Ｂ］～［６Ｂ］のいずれかに記載の方法。
［８Ｂ］ 組成物の剤形が、錠剤、カプセル剤、顆粒剤及び散剤よりなる群から選ばれる剤形である、［１Ｂ］～［７Ｂ］のいずれかに記載の方法。
［９Ｂ］ 組成物が胃腸薬である、［１Ｂ］～［８Ｂ］のいずれかに記載の方法。
[1B] The following component (A):
(A) methylmethionine sulfonium chloride;
and the following component (B):
(B) one or more selected from the group consisting of magnolia bark and extracts thereof;
A method for stabilizing methylmethionine sulfonium chloride in a composition, comprising the step of incorporating the above in the same composition.
[2B] The method according to [1B], wherein the extract of Magnolia bark is obtained by using a solvent selected from the group consisting of water, a lower monohydric alcohol, and a mixture thereof as an extraction solvent.
[3B] Furthermore, one or more selected from the group consisting of the following components (C) and (D);
(C) one or more selected from the group consisting of Perilla japonica and extracts thereof;
(D) starches;
The method according to [1B] or [2B], wherein the above are contained in the same composition.
[4B] The method according to [3B], wherein the extract of Perilla herb is obtained by using a solvent selected from the group consisting of water, a lower monohydric alcohol, and a mixture thereof as an extraction solvent.
[5B] The method according to [3B] or [4B], wherein the starches are one or more selected from the group consisting of starch, hydroxy C1-C6 alkyl ether of starch, carboxy C1-C6 alkyl ether of starch, and salts thereof.
[6B] The method according to any one of [3B] to [5B], wherein the starches are one or more selected from the group consisting of starch, hydroxypropyl starch, carboxymethyl starch, and salts thereof.
[7B] The method according to any one of [1B] to [6B], wherein the composition is a solid composition.
[8B] The method according to any one of [1B] to [7B], wherein the composition is in a dosage form selected from the group consisting of tablets, capsules, granules, and powders.
[9B] The method according to any one of [1B] to [8B], wherein the composition is a gastrointestinal drug.
以下に実施例を挙げて本発明を詳細に説明するが、本発明はこれら実施例に何ら限定されるものではない。 The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.
［試験例１］安定性試験
以下に示すサンプル１～３をそれぞれ調製後、８０℃で１日間保存し、保存前後のサンプル中のＭＭＳＣの含量を、ＨＰＬＣ装置を用いて内標準法により定量した。得られた測定値より、各サンプルの８０℃１日保存後のＭＭＳＣの含量を、試験開始時における含量を１００％としたときの相対値（残存率：％）として評価した。
結果を表１に示す。
[Test Example 1] Stability test Samples 1 to 3 shown below were prepared and stored at 80°C for 1 day, and the MMSC content in the samples before and after storage was quantified by an internal standard method using an HPLC device. From the obtained measurements, the MMSC content of each sample after storage at 80°C for 1 day was evaluated as a relative value (residual rate: %) when the content at the start of the test was taken as 100%.
The results are shown in Table 1.
〔サンプル１〕
ＭＭＳＣ（ＭＭＳＣ：米沢浜理薬品工業(株)）１ｇを、プラスチック製の容器に入れ、そのままサンプル１とした。
〔サンプル２〕
ＭＭＳＣ（ＭＭＳＣ：米沢浜理薬品工業(株)）１ｇとコウボク乾燥エキス（コウボク乾燥エキス：日本粉末薬品(株)）１ｇを混合し、得られた混合物をプラスチック製の容器に入れ、サンプル２とした。
〔サンプル３〕
ＭＭＳＣ（ＭＭＳＣ：米沢浜理薬品工業(株)）１ｇ、コウボク乾燥エキス（コウボク乾燥エキス：日本粉末薬品(株)）１ｇ、ソヨウ乾燥エキス（ソヨウ乾燥エキス－Ｑ：日本粉末薬品(株)）１ｇを混合し、得られた混合物をプラスチック製の容器に入れ、サンプル３とした。
[Sample 1]
1 g of MMSC (MMSC: Yonezawa Hamari Chemicals Co., Ltd.) was placed in a plastic container and used as Sample 1.
[Sample 2]
1 g of MMSC (MMSC: Yonezawa Hamari Pharmaceutical Co., Ltd.) and 1 g of Magnolia bark dried extract (Magnolia bark dried extract: Nippon Powder Pharmaceutical Co., Ltd.) were mixed, and the resulting mixture was placed in a plastic container and used as sample 2.
[Sample 3]
1 g of MMSC (MMSC: Yonezawa Hamari Pharmaceutical Co., Ltd.), 1 g of Magnolia bark dried extract (Magnolia bark dried extract: Nippon Powder Pharmaceutical Co., Ltd.), and 1 g of Perilla japonica dried extract (Perilla japonica dried extract-Q: Nippon Powder Pharmaceutical Co., Ltd.) were mixed and the resulting mixture was placed in a plastic container and used as Sample 3.
表１記載の結果より、サンプル１（ＭＭＳＣのみ）においては８０℃、１日保存後のＭＭＳＣの残存率が９１％であったのに対し、サンプル２（ＭＭＳＣとコウボク乾燥エキスの混合物）においてはＭＭＳＣの残存率が９４％と向上しており、ＭＭＳＣの含量低下が抑制されることが明らかとなった。
また、サンプル３（ＭＭＳＣ、コウボク乾燥エキス、ソヨウ乾燥エキスの混合物）においてはＭＭＳＣの残存率が１００％とさらに向上しており、ＭＭＳＣの含量低下がより一層抑制されることが明らかとなった。
As shown in Table 1, in sample 1 (MMSC only), the MMSC survival rate after storage at 80°C for 1 day was 91%, whereas in sample 2 (mixture of MMSC and magnolia bark dried extract), the MMSC survival rate improved to 94%, demonstrating that the decrease in MMSC content was suppressed.
Furthermore, in sample 3 (a mixture of MMSC, Magnolia bark dried extract, and Perilla herb dried extract), the survival rate of MMSC was further improved to 100%, demonstrating that the decrease in MMSC content was further suppressed.
以上の試験結果より、コウボク及びその抽出物よりなる群から選ばれる１種以上が、ＭＭＳＣの含量低下を抑制する作用を有することが明らかとなった。また、ＭＭＳＣ、コウボク及びその抽出物よりなる群から選ばれる１種以上に加えて、さらにソヨウ及びその抽出物よりなる群から選ばれる１種以上を共存せしめることにより、ＭＭＳＣの含量低下をより一層抑制できることが明らかとなった。 The above test results demonstrate that one or more selected from the group consisting of Magnolia bark and its extracts have the effect of suppressing the decrease in MMSC content. It also demonstrates that the coexistence of one or more selected from the group consisting of Perilla japonica and its extracts in addition to one or more selected from the group consisting of MMSC, Magnolia bark and its extracts can further suppress the decrease in MMSC content.
［試験例２］安定性試験 その２
以下に示すサンプル４を調製後、試験例１と同様の方法により試験を実施した。
結果を表２に示す。
[Test Example 2] Stability test No. 2
Sample 4 shown below was prepared and then tested in the same manner as in Test Example 1.
The results are shown in Table 2.
〔サンプル４〕
ＭＭＳＣ（ＭＭＳＣ：米沢浜理薬品工業(株)）１ｇ、コウボク乾燥エキス（コウボク乾燥エキス：日本粉末薬品(株)）１ｇ、トウモロコシデンプン（トウモロコシデンプンＳＴ－Ｃ：日澱化学（株））１ｇを混合し、得られた混合物をプラスチック製の容器に入れ、サンプル４とした。
[Sample 4]
1 g of MMSC (MMSC: Yonezawa Hamari Pharmaceutical Co., Ltd.), 1 g of Magnolia bark dried extract (Magnolia bark dried extract: Nippon Powder Pharmaceutical Co., Ltd.), and 1 g of corn starch (Corn starch ST-C: Nippon Starch Chemical Co., Ltd.) were mixed, and the resulting mixture was placed in a plastic container and used as Sample 4.
表２記載の結果より、サンプル４（ＭＭＳＣ、コウボク乾燥エキス、トウモロコシデンプンの混合物）においても試験例１のサンプル３と同様、ＭＭＳＣの残存率が９９％と極めて高い値となった。 The results shown in Table 2 indicate that sample 4 (a mixture of MMSCs, Magnolia bark dry extract, and corn starch) also had an extremely high MMSC survival rate of 99%, similar to sample 3 in Test Example 1.
以上の試験結果より、ＭＭＳＣ、コウボク及びその抽出物よりなる群から選ばれる１種以上に加えて、さらにデンプン類を共存せしめることにより、ＭＭＳＣの含量低下をより一層抑制できることが明らかとなった。 These test results demonstrate that the decrease in MMSC content can be further suppressed by adding starches to one or more selected from the group consisting of MMSC, magnolia bark and its extracts.
［製造例１］
１錠（７００ｍｇ）当りに以下の成分を含有する有核錠を、常法に従って製造した。製造した有核錠１００錠をプラスチック容器（ポリエチレン製の１０Ｋ規格瓶）に収容した。
メチルメチオニンスルホニウムクロライド ２５ｍｇ
ロートエキス３倍散 １５ｍｇ
センブリ末 ４．７ｍｇ
ソヨウ乾燥エキス ３．３ｍｇ（原生薬換算量３０ｍｇ）
コウボク乾燥エキス ２．５ｍｇ（原生薬換算量３０ｍｇ）
ビオジアスターゼ２０００ ４ｍｇ
リパーゼＡＰ１２ ２．５ｍｇ
炭酸水素ナトリウム １００ｍｇ
沈降炭酸カルシウム ２２３ｍｇ
水酸化マグネシウム ３５ｍｇ
ヒドロキシプロピルセルロース
硬化油
カルメロースカルシウム
トウモロコシデンプン
ステアリン酸マグネシウム
ステアリン酸グリセリン
ステアリン酸ポリオキシル
セラック
タルク
ケイヒ
ポリビニルアルコール（部分けん化物）
Ｄ－マンニトール
セルロース
二酸化ケイ素
ｌ－メントール
[Production Example 1]
Dry-coated tablets containing the following ingredients per tablet (700 mg) were produced according to a conventional method. 100 dry-coated tablets produced were placed in a plastic container (a 10K standard polyethylene bottle).
Methylmethionine sulfonium chloride 25mg
Scopolia extract triple powder 15mg
Swertia japonica powder 4.7mg
Perilla dried extract 3.3mg (equivalent to 30mg of crude drug)
Magnolia bark dry extract 2.5mg (equivalent to 30mg of raw herb)
Biodiastase 2000 4mg
Lipase AP12 2.5mg
Sodium bicarbonate 100mg
Precipitated calcium carbonate 223mg
Magnesium hydroxide 35mg
Hydroxypropyl cellulose, hydrogenated oil, carmellose calcium, corn starch, magnesium stearate, glycerin stearate, polyoxyl stearate, shellac, talc, cinnamon, polyvinyl alcohol (partially saponified)
D-mannitol cellulose silicon dioxide l-menthol
［製造例２］
１錠（６８０ｍｇ）当りに以下の成分を含有する有核錠を、常法に従って製造した。製造した有核錠２００錠をプラスチック容器（ポリエチレン製の１２Ｋ規格瓶）に収容した。
メチルメチオニンスルホニウムクロライド ２５ｍｇ
ロートエキス３倍散 １５ｍｇ
センブリ末 ４．７ｍｇ
ソヨウ乾燥エキス ３．３ｍｇ（原生薬換算量３０ｍｇ）
コウボク乾燥エキス ２．５ｍｇ（原生薬換算量３０ｍｇ）
ビオジアスターゼ２０００ ４ｍｇ
リパーゼＡＰ１２ ２．５ｍｇ
炭酸水素ナトリウム １００ｍｇ
沈降炭酸カルシウム ２２３ｍｇ
水酸化マグネシウム ３５ｍｇ
ヒドロキシプロピルセルロース
硬化油
カルメロースカルシウム
トウモロコシデンプン
ステアリン酸マグネシウム
ステアリン酸グリセリン
ステアリン酸ポリオキシル
セラック
タルク
ケイヒ
ポリビニルアルコール（部分けん化物）
セルロース
二酸化ケイ素
ｌ－メントール
[Production Example 2]
Dry-coated tablets containing the following ingredients per tablet (680 mg) were produced according to a conventional method. 200 of the produced dry-coated tablets were placed in a plastic container (a 12K standard polyethylene bottle).
Methylmethionine sulfonium chloride 25mg
Scopolia extract triple powder 15mg
Swertia japonica powder 4.7mg
Perilla dried extract 3.3mg (equivalent to 30mg of crude drug)
Magnolia bark dry extract 2.5mg (equivalent to 30mg of raw herbal medicine)
Biodiastase 2000 4mg
Lipase AP12 2.5mg
Sodium bicarbonate 100mg
Precipitated calcium carbonate 223mg
Magnesium hydroxide 35mg
Hydroxypropyl cellulose, hydrogenated oil, carmellose calcium, corn starch, magnesium stearate, glycerin stearate, polyoxyl stearate, shellac, talc, cinnamon, polyvinyl alcohol (partially saponified)
Cellulose Silicon dioxide l-menthol
［製造例３］
１錠（６９０ｍｇ）当りに以下の成分を含有する有核錠を、常法に従って製造した。製造した有核錠３００錠をプラスチック容器（ポリエチレン製の１４Ｋ規格瓶）に収容した。
メチルメチオニンスルホニウムクロライド ２５ｍｇ
ロートエキス３倍散 １５ｍｇ
センブリ末 ４．７ｍｇ
ソヨウ乾燥エキス ３．３ｍｇ（原生薬換算量３０ｍｇ）
コウボク乾燥エキス ２．５ｍｇ（原生薬換算量３０ｍｇ）
ビオジアスターゼ２０００ ４ｍｇ
リパーゼＡＰ１２ ２．５ｍｇ
炭酸水素ナトリウム １００ｍｇ
沈降炭酸カルシウム ２２３ｍｇ
水酸化マグネシウム ３５ｍｇ
ヒドロキシプロピルセルロース
硬化油
カルメロースカルシウム
トウモロコシデンプン
ステアリン酸マグネシウム
ステアリン酸グリセリン
ステアリン酸ポリオキシル
セラック
タルク
ケイヒ
ポリビニルアルコール（部分けん化物）
還元麦芽糖水アメ
セルロース
二酸化ケイ素
ｌ－メントール
[Production Example 3]
Dry-coated tablets containing the following ingredients per tablet (690 mg) were produced according to a conventional method. 300 of the produced dry-coated tablets were placed in a plastic container (a 14K standard polyethylene bottle).
Methylmethionine sulfonium chloride 25mg
Scopolia extract triple powder 15mg
Swertia japonica powder 4.7mg
Perilla dried extract 3.3mg (equivalent to 30mg of crude drug)
Magnolia bark dry extract 2.5mg (equivalent to 30mg of raw herb)
Biodiastase 2000 4mg
Lipase AP12 2.5mg
Sodium bicarbonate 100mg
Precipitated calcium carbonate 223mg
Magnesium hydroxide 35mg
Hydroxypropyl cellulose, hydrogenated oil, carmellose calcium, corn starch, magnesium stearate, glycerin stearate, polyoxyl stearate, shellac, talc, cinnamon, polyvinyl alcohol (partially saponified)
Reduced maltose, water cellulose, silicon dioxide, l-menthol
［製造例４］
１包（１３００ｍｇ）当りに以下の成分を含有する顆粒剤を、常法に従って製造し、アルミピロー包装した。
メチルメチオニンスルホニウムクロライド ５０ｍｇ
ロートエキス３倍散 ３０ｍｇ
センブリ末 ９．３ｍｇ
ソヨウ乾燥エキス ６．６ｍｇ（原生薬換算量６０ｍｇ）
コウボク乾燥エキス ５ｍｇ（原生薬換算量６０ｍｇ）
ビオジアスターゼ２０００ ８ｍｇ
リパーゼＡＰ１２ ５ｍｇ
炭酸水素ナトリウム ２００ｍｇ
沈降炭酸カルシウム ４４７ｍｇ
水酸化マグネシウム ７０ｍｇ
硬化油
ヒドロキシプロピルセルロース
Ｄ－マンニトール
カルメロースカルシウム
乳酸カルシウム
スクラロース
ｌ－メントール
二酸化ケイ素
香料
トウモロコシデンプン
[Production Example 4]
Granules containing the following ingredients per packet (1,300 mg) were prepared according to a conventional method and packed in aluminum pillow bags.
Methylmethionine sulfonium chloride 50mg
Scopolia extract triple powder 30mg
Swertia japonica powder 9.3mg
Perilla dried extract 6.6mg (equivalent to 60mg of crude drug)
Magnolia bark dry extract 5mg (equivalent to 60mg of raw herb)
Biodiastase 2000 8mg
Lipase AP12 5mg
Sodium bicarbonate 200mg
Precipitated calcium carbonate 447mg
Magnesium hydroxide 70mg
Hydrogenated oil Hydroxypropyl cellulose D-mannitol Carmellose calcium Calcium lactate Sucralose l-menthol Silicon dioxide Flavoring Corn starch
本発明によれば、メチルメチオニンスルホニウムクロライドの含量低下が抑制され安定性が改善された、品質安定性の良好な組成物を提供でき、医薬品産業・医薬部外品産業等において利用できる。 According to the present invention, a composition with good quality and stability can be provided in which the decrease in the content of methylmethionine sulfonium chloride is suppressed and stability is improved, and the composition can be used in the pharmaceutical and quasi-drug industries, etc.
Claims (3)
（Ａ）メチルメチオニンスルホニウムクロライド；
（Ｂ）コウボク及びその抽出物よりなる群から選ばれる１種以上；
（Ｃ）ソヨウ及びその抽出物よりなる群から選ばれる１種以上；
を含有し、固形状である、組成物（但し、コウボク及びニッケイ抽出物とメチルメチオニンスルホニウムクロライド、無花果及びリパーゼとを含む、腸内消化酵素活性及び発現を促進させる組成物を除く）。 The following components (A) , (B) and (C) :
(A) methylmethionine sulfonium chloride;
(B) one or more selected from the group consisting of magnolia bark and extracts thereof;
(C) one or more selected from the group consisting of Perilla japonica and extracts thereof;
and being in a solid form (excluding the composition for promoting intestinal digestive enzyme activity and expression comprising magnolia bark and cinnamon extract, methylmethionine sulfonium chloride, fig and lipase).
（Ｄ）デンプン類；
を含有する、請求項１に記載の組成物。 Furthermore, the following component (D):
(D) starches;
The composition of claim 1 comprising:
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