JP2015218130A - Poaceae plant extract having enteral flora control ability - Google Patents
Poaceae plant extract having enteral flora control ability Download PDFInfo
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- JP2015218130A JP2015218130A JP2014101979A JP2014101979A JP2015218130A JP 2015218130 A JP2015218130 A JP 2015218130A JP 2014101979 A JP2014101979 A JP 2014101979A JP 2014101979 A JP2014101979 A JP 2014101979A JP 2015218130 A JP2015218130 A JP 2015218130A
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- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
本発明は、腸内フローラ調整能を有するイネ科植物抽出物に関する。腸内フローラ調整能とは、高脂肪食の摂取などに起因する腸内フローラ構成の変化を抑制し、健常時の腸内フローラ構成を維持し得る作用である。 The present invention relates to a grass plant extract having an ability to adjust intestinal flora. The intestinal flora adjusting ability is an action that can suppress changes in the intestinal flora configuration caused by ingestion of a high-fat diet and maintain a normal intestinal flora configuration.
ヒトの腸内には、100種類以上の腸内細菌が約100兆個以上存在しており、それらの腸内細菌は、宿主であるヒトが摂取した食餌に含まれる栄養分の一部を利用して生活し、他の種類の腸内細菌との間で数のバランスを保ちながら、腸内フローラあるいは腸内細菌叢などと呼ばれる一種の生態系を形成している。腸内フローラを構成する腸内細菌には、宿主に対して有益に働き腸内環境を改善し得る腸内有用菌(いわゆる善玉菌)と、宿主に対して害を及ぼし得る腸内有害菌(いわゆる悪玉菌)とがあり、宿主の健常時において両者は一定の数のバランスを保っているが、脂肪過多の食生活などが原因でそのバランスが崩れて悪玉菌が増えると腸内腐敗が促進され、それによって、便秘・下痢症状の発症、免疫機能の低下、老化促進、発ガン性物質の生成などの不都合が起こり得る。そこで、腸内環境を改善する食品因子の探索が盛んに行われており、例えば食物繊維やオリゴ糖などが知られている。 There are about 100 trillion or more types of intestinal bacteria in the human intestine, and these enterobacteria use part of the nutrients contained in the diet taken by the host human. It forms a kind of ecosystem called intestinal flora or intestinal microflora while maintaining the number balance with other types of intestinal bacteria. The enteric bacteria that make up the intestinal flora include useful intestinal bacteria (so-called good bacteria) that can beneficially work on the host and improve the intestinal environment, and enteric harmful bacteria that can harm the host ( So-called bad bacteria) and both maintain a certain number of balances in the normal state of the host, but intestinal rot promotes when the number of bad bacteria increases due to a loss of the balance due to a diet of excessive fat, etc. As a result, inconveniences such as the onset of symptoms of constipation / diarrhea, decreased immune function, accelerated aging, and generation of carcinogenic substances may occur. Therefore, search for food factors that improve the intestinal environment has been actively conducted, and for example, dietary fibers and oligosaccharides are known.
例えば特許文献1には、魚介類であるタコから内臓を除去したものを凍結乾燥し粉末化して得られる、タコ粉末を有効成分として含有する整腸作用組成物が、腸内の善玉菌であるLactobacillales属の細菌を増加させる作用を有することが記載されている。この整腸作用組成物によれば、Lactobacillales属の善玉菌の増加に伴い、大半が悪玉菌として知られているClostridium属の細菌が減少するので、腸内環境が改善されるとされている。 For example, in Patent Document 1, an intestinal regulating composition containing octopus powder as an active ingredient, which is obtained by freeze-drying and pulverizing an octopus which is a seafood, is a good bacteria in the intestine. It is described that it has an action of increasing bacteria of the genus Lactobacilles. According to this composition for regulating intestines, with the increase of good bacteria of the genus Lactobacilles, the bacteria of the genus Clostridium known as bad bacteria are reduced, and therefore the intestinal environment is said to be improved.
また特許文献2には、糖吸収抑制物質を少なくとも1種含有する腸内細菌叢構成比率調整剤が、バクテロイデス門(Bacteroidetes)の細菌を増殖させ、ファーミキューテス門(Firmicutes)の細菌を減少させる作用を有することが記載されている。近年の研究により、ヒトにおいて肥満時はバクテロイデス門に属する菌の構成比率が低く、ファーミキューテス門に属する菌の構成比率が高い状態になっており、体重減少に伴い、バクテロイデス門の構成比率が高まり、逆にファーミキューテス門の構成比率が低下することが明らかになっており、また、やせている人は太っている人と比較して、バクテロイデス門の構成比率が高く、ファーミキューテス門の構成比率が低いことも明らかになっており、特許文献2は、斯かる研究結果に基づくものである。特許文献2記載の腸内細菌叢構成比率調整剤に含まれる糖吸収抑制物質は、サラシア属植物、桑葉、ギムネマ又はこれらの抽出物に含まれる成分であり、小麦由来の物質ではない。
Further, in
また非特許文献1には、マウスに高脂肪食を負荷したことに起因する腸内細菌叢の乱れに対して、アスタキサンチン投与が制御的に作用することが記載されている。アスタキサンチンは、天然色素であるカロテノイドの一種であり、甲殻類の殻やそれらを餌とする魚の体表、サケ科魚類の筋肉の赤色部分などに見られる。 Non-Patent Document 1 describes that astaxanthin administration acts on the disturbance of the intestinal bacterial flora caused by loading a mouse with a high fat diet. Astaxanthin is a kind of carotenoid that is a natural pigment, and is found in shells of crustaceans, the body surface of fish that feed them, and the red part of muscles of salmonid fish.
従来素材の腸内フローラ調整作用は、必ずしも十分満足のいくものとは限らなかった。高脂肪食の摂取などに起因する腸内フローラ構成の変化を抑制し、健常時の腸内フローラ構成を維持し得る効果に優れ、且つ安全で副作用が少なく、医薬品、飲食品、飼料等として利用可能な素材は未だ提供されていない。 The intestinal flora adjusting action of the conventional material is not always satisfactory. Suppress changes in the intestinal flora composition caused by ingestion of high-fat foods, etc., have excellent effects that can maintain the normal intestinal flora composition, and are safe and have few side effects, and can be used as pharmaceuticals, foods and drinks, feeds, etc. Possible materials have not yet been provided.
本発明は、安全で副作用の少ない、腸内フローラ調整能を有するイネ科植物抽出物に関する。 The present invention relates to a gramineous plant extract that is safe and has few side effects and has the ability to adjust intestinal flora.
Peterらは、肥満マウスの腸内フローラは、食事からエネルギーを取り込む能力が高く、それゆえ肥満が誘導されること(参考文献1参照)、及び、肥満マウスの腸内フローラ構成は、肥満ではない健常マウスのそれに比して、悪玉菌であるバクトロイデス属の細菌の割合が少なく且つ悪玉菌であるエンテロコッカス属の細菌の割合が多い傾向があること(参考文献2参照)を報告している。また、本発明者らの検討においても同様の傾向が確認されており、高脂肪高ショ糖食を一定期間摂取したマウス群の腸内フローラ構成は、普通食を一定期間摂取したマウス群のそれに比して、バクテロイデス属の細菌の割合が少なく且つ悪玉菌であるエンテロコッカス属の細菌の割合が多かった。そして、本発明者らは、前記課題を解決すべく鋭意検討した結果、イネ科植物の一種である小麦ふすまのエタノール抽出物であってアルキルレゾルシノールを含有するものが腸内フローラ調整能を有し、これを摂取することにより、生体への悪影響が報告されているバクトロイデス属及びエンテロコッカス属の細菌の、高脂肪食摂取によるバランス変動幅が大幅に低減し、腸内フローラ構成が高脂肪食摂取前の健常時のそれに近づくことを知見した。 Peter et al. Show that the intestinal flora of obese mice has a high ability to take energy from the diet, and therefore obesity is induced (see Reference 1), and the intestinal flora configuration of obese mice is not obese. It has been reported that the proportion of bacteria of the genus Bactoroides which are bad bacteria and the proportion of bacteria of the genus Enterococcus which are bad bacteria tend to be larger than that of healthy mice (see Reference 2). In addition, the same tendency has been confirmed in the study by the present inventors, and the intestinal flora composition of the group of mice ingesting the high-fat and high-sucrose diet for a certain period is similar to that of the group of mice ingesting the normal diet for a certain period. In comparison, the proportion of Bacteroides bacteria was small and the proportion of Enterococcus bacteria, which are bad bacteria, was large. And as a result of intensive studies to solve the above problems, the present inventors have found that an ethanol extract of wheat bran, which is a kind of gramineous plant, containing alkylresorcinol has the ability to adjust intestinal flora. Ingestion of Bacteroides and Enterococcus bacteria, which have been reported to have adverse effects on living organisms, greatly reduces the range of balance fluctuation due to intake of a high-fat diet, and the intestinal flora composition before intake of a high-fat diet I found out that it approaches that of normal health.
参考文献1:Peter J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. 2006 Nature. 444(7122):1027-31.
参考文献2:Peter J. et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. 2009 Sci Transl Med. 1(6):6ra14.
Reference 1: Peter J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. 2006 Nature. 444 (7122): 1027-31.
Reference 2: Peter J. et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. 2009 Sci Transl Med. 1 (6): 6ra14.
本発明は、前記知見に基づきなされたもので、イネ科植物からアルコールを用いて抽出された、腸内フローラ調整能を有するイネ科植物抽出物である。
また本発明は、前記イネ科植物抽出物を含有する医薬品又は飲食品である。
This invention is made | formed based on the said knowledge, It is the gramineous plant extract which has the ability to adjust intestinal flora extracted from the gramineous plant using alcohol.
Moreover, this invention is the pharmaceutical or food-drinks containing the said Gramineae plant extract.
本発明のイネ科植物抽出物は、腸内フローラ調整能を有し、高脂肪食の摂取などに起因する腸内フローラ構成の変化を抑制し、健常時の腸内フローラ構成を維持し得る。また、本発明のイネ科植物抽出物は、食経験が豊富な小麦やライ麦などのイネ科植物に含まれている成分を主体とするものであることから、長期間継続的に摂取しても生体に有害な作用をもたらす懸念が少なく、安全性が高く副作用のおそれが少ない。 The grass plant extract of the present invention has the ability to adjust the intestinal flora, suppresses changes in the intestinal flora configuration caused by ingestion of a high fat diet, and can maintain a normal intestinal flora configuration. In addition, the gramineous plant extract of the present invention is mainly composed of ingredients contained in gramineous plants such as wheat and rye that have abundant dietary experience. There are few concerns that cause harmful effects on the living body, and it is highly safe and has a low risk of side effects.
腸内フローラ調整能を有する本発明のイネ科植物抽出物は、イネ科植物のアルコール抽出物である。抽出源であるイネ科植物としては、特に制限されないが、例えば、小麦、ライ麦、ライ小麦、大麦、オーツ麦、はと麦、トウモロコシ、ヒエ、アワ、キビ等の穀類が挙げられ、これらの1種を単独で又は2種以上を組み合わせて用いることができる。これらの穀類の中でも特に小麦及びライ麦が好ましい。小麦の種類は特に制限されない。また、抽出源であるイネ科植物は、通常、その頴果を用い、抽出源であるイネ科植物が小麦の場合は、小麦粒を用いる。本発明では、イネ科植物の頴果又はその乾燥物をその粒の形状を維持したまま抽出源として用いても良く、あるいは、頴果又はその乾燥物を切断、粉砕等して得られる細片、粉砕物(粉末)を抽出源として用いても良い。 The gramineous plant extract of the present invention having the ability to adjust intestinal flora is an alcoholic extract of gramineous plants. Grains such as wheat, rye, rye, barley, oats, corn, corn, barnyard millet, millet, millet, and the like can be cited as examples of Gramineae plants that are extraction sources. Species can be used alone or in combination of two or more. Among these cereals, wheat and rye are particularly preferable. The type of wheat is not particularly limited. Moreover, the gramineous plant which is an extraction source normally uses the fruit, and when the gramineous plant which is an extraction source is wheat, wheat grain is used. In the present invention, berries of gramineous plants or dried products thereof may be used as an extraction source while maintaining the shape of the grains, or strips obtained by cutting, pulverizing, etc. A pulverized product (powder) may be used as an extraction source.
抽出源であるイネ科植物は、頴果の外皮(果皮、種皮)を含んでいることが好ましい。本発明で抽出源として好ましく用いられるものとして、小麦全粒粉、ライ麦全粒粉、小麦ふすま、ライ麦外皮が挙げられ、特に、入手の容易さや価格等の点から小麦ふすまが好ましい。 It is preferable that the Gramineae plant which is an extraction source contains an outer skin (fruit skin, seed coat) of fruit juice. Wheat bran is preferable from the standpoints of availability, price, and the like as wheat flour, rye whole flour, wheat bran, and rye hulls that are preferably used as the extraction source in the present invention.
イネ科植物の抽出に用いるアルコールとしては、例えば、メタノール、エタノール、n−プロパノール、イソプロパノール、n−ブタノール等の1価の低級アルコール(好ましくは炭素原子数1〜4のもの)、及び1,3−ブチレングリコール、プロピレングリコール、グリセリン等の多価アルコール等の室温(25℃)で液体であるアルコールが挙げられる。ここでいうアルコールには、アルコールに加えてさらに水、純水、蒸留水、水道水、酸性水、アルカリ水、中性水等の水性成分を含む、含水アルコールが包含される。含水アルコール中のアルコール含有量は、通常70体積%以上、好ましくは80体積%以上、より好ましくは90体積%以上である。これらのアルコールの中でも特に、操作性や環境性の点から、エタノール(含水エタノール)が好ましい。 Examples of alcohols used for the extraction of gramineous plants include monovalent lower alcohols (preferably those having 1 to 4 carbon atoms) such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and 1,3. -Alcohol which is liquid at room temperature (25 degreeC), such as polyhydric alcohols, such as butylene glycol, propylene glycol, and glycerol. As used herein, the alcohol includes water-containing alcohols containing aqueous components such as water, pure water, distilled water, tap water, acidic water, alkaline water, and neutral water in addition to alcohol. The alcohol content in the hydrous alcohol is usually 70% by volume or more, preferably 80% by volume or more, more preferably 90% by volume or more. Among these alcohols, ethanol (hydrous ethanol) is particularly preferable from the viewpoint of operability and environmental performance.
イネ科植物のアルコールによる抽出方法は特に制限されないが、例えば、小麦粒又はその細片若しくは粉砕物をアルコール中に浸漬、攪拌又は還流する方法の他、超臨界流体抽出法等が挙げられる。例えば、小麦ふすまをエタノール(含水エタノール)中に浸漬、攪拌又は還流する方法の場合、抽出温度(エタノールの液温)は好ましくは2〜80℃、抽出時間は0.5〜72時間、エタノール使用量は小麦ふすま100質量部に対し好ましくは50〜2000質量部である。 The method for extracting grass plants with alcohol is not particularly limited, and examples thereof include a supercritical fluid extraction method and the like in addition to a method of immersing, stirring or refluxing wheat grains or fine pieces or pulverized products thereof in alcohol. For example, in the case of a method in which wheat bran is immersed, stirred or refluxed in ethanol (hydrous ethanol), the extraction temperature (ethanol liquid temperature) is preferably 2 to 80 ° C., the extraction time is 0.5 to 72 hours, and ethanol is used. The amount is preferably 50 to 2000 parts by mass with respect to 100 parts by mass of wheat bran.
本発明のイネ科植物抽出物は、好ましくはアルキルレゾルシノールを有効成分として含有する。本発明者らの知見によれば、本発明のイネ科植物抽出物が有する腸内フローラ調整能は、下記一般式(I)で表されるアルキルレゾルシノールの作用によるところが大きい。本発明のイネ科植物抽出物は、下記一般式(I)で表されるアルキルレゾルシノールの1種又は2種以上を有効成分として含有することが好ましい。本発明のイネ科植物抽出物における下記一般式(I)で表されるアルキルレゾルシノールの含有量は、腸内フローラ調整効果をより確実に奏させるようにする観点から、本発明のイネ科植物抽出物中、好ましくは70質量%以上、更に好ましくは80質量%以上である。下記一般式(I)で表されるアルキルレゾルシノールの含有量は100質量%、即ち、本発明のイネ科植物抽出物は下記一般式(I)で表されるアルキルレゾルシノールのみから構成されていても良い。 The grass plant extract of the present invention preferably contains alkylresorcinol as an active ingredient. According to the knowledge of the present inventors, the ability to adjust the intestinal flora of the grass plant extract of the present invention is largely due to the action of alkylresorcinol represented by the following general formula (I). The grass plant extract of the present invention preferably contains one or more alkylresorcinol represented by the following general formula (I) as an active ingredient. The content of the alkylresorcinol represented by the following general formula (I) in the grass plant extract of the present invention is the grass plant extract of the present invention from the viewpoint of more surely exerting an intestinal flora adjusting effect. In the product, it is preferably 70% by mass or more, more preferably 80% by mass or more. The content of the alkylresorcinol represented by the following general formula (I) is 100% by mass, that is, the grass plant extract of the present invention may be composed of only the alkylresorcinol represented by the following general formula (I). good.
前記一般式(I)におけるR1に関し、炭素原子数15〜25の飽和アルキル基としては、代表例として、n−ペンタデシル、n−ヘプタデシル、n−ノナデシル、n−ヘンイコシル、n−トリコシル、n−ペンタコシル、n−ヘプタコシル等の直鎖状のものが挙げられ、これらの他に、分岐状又は環状のものでも良い。これらの中でも、炭素原子数15〜23の飽和アルキル基が好ましい。 Regarding R 1 in the general formula (I), examples of the saturated alkyl group having 15 to 25 carbon atoms include n-pentadecyl, n-heptadecyl, n-nonadecyl, n-henicosyl, n-tricosyl, n- Examples include linear ones such as pentacosyl and n-heptacosyl, and besides these, branched or cyclic ones may be used. Among these, a saturated alkyl group having 15 to 23 carbon atoms is preferable.
また、前記一般式(I)におけるR1に関し、炭素原子数15〜25の不飽和アルキル基としては、前記の炭素原子数15〜25の飽和アルキル基に対応するものが挙げられる。不飽和アルキル基に含まれる不飽和結合の数及び位置に特に制限はない。 Moreover, regarding R 1 in the general formula (I), examples of the unsaturated alkyl group having 15 to 25 carbon atoms include those corresponding to the saturated alkyl group having 15 to 25 carbon atoms. There is no restriction | limiting in particular in the number and position of the unsaturated bond contained in an unsaturated alkyl group.
また、前記一般式(I)におけるR2は水素原子であることが好ましく、また、R1はR2に対してパラ位に結合していることが好ましい。 In the general formula (I), R 2 is preferably a hydrogen atom, and R 1 is preferably bonded to R 2 at the para position.
本発明のイネ科植物抽出物に含まれ得るアルキルレゾルシノールの具体例としては、以下のものが挙げられる。
1,3−ジヒドロキシ−5−n−ペンタデシルベンゼン(C15:0)
1,3−ジヒドロキシ−5−n−ヘプタデシルベンゼン(C17:0)
1,3−ジヒドロキシ−5−n−ノナデシルベンゼン(C19:0)
1,3−ジヒドロキシ−5−n−ヘンイコシルベンゼン(C21:0)
1,3−ジヒドロキシ−5−n−トリコシルベンゼン(C23:0)
1,3−ジヒドロキシ−5−n−ペンタコシルベンゼン(C25:0)
Specific examples of the alkyl resorcinol that can be contained in the grass plant extract of the present invention include the following.
1,3-dihydroxy-5-n-pentadecylbenzene (C15: 0)
1,3-dihydroxy-5-n-heptadecylbenzene (C17: 0)
1,3-dihydroxy-5-n-nonadecylbenzene (C19: 0)
1,3-dihydroxy-5-n-henicosylbenzene (C21: 0)
1,3-dihydroxy-5-n-tricosylbenzene (C23: 0)
1,3-dihydroxy-5-n-pentacosylbenzene (C25: 0)
本発明のイネ科植物抽出物の好ましい一例として、下記6種類のアルキルレゾルシノールを含有するものが挙げられる。
1)前記一般式(I)におけるR1が炭素原子数15の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR15ともいう)。
2)前記一般式(I)におけるR1が炭素原子数17の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR17ともいう)。
3)前記一般式(I)におけるR1が炭素原子数19の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR19ともいう)。
4)前記一般式(I)におけるR1が炭素原子数21の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR21ともいう)。
5)前記一般式(I)におけるR1が炭素原子数23の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR23ともいう)。
6)前記一般式(I)におけるR1が炭素原子数25の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR25ともいう)。
As a preferable example of the gramineous plant extract of the present invention, those containing the following 6 types of alkylresorcinol can be mentioned.
1) Alkyl resorcinol (hereinafter, also referred to as AR15) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 15 carbon atoms.
2) Alkyl resorcinol (hereinafter, also referred to as AR17) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 17 carbon atoms.
3) Alkyl resorcinol (hereinafter, also referred to as AR19) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 19 carbon atoms.
4) Alkyl resorcinol (hereinafter, also referred to as AR21) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 21 carbon atoms.
5) Alkyl resorcinol (hereinafter also referred to as AR23) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 23 carbon atoms.
6) Alkyl resorcinol (hereinafter also referred to as AR25) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 25 carbon atoms.
AR15として特に好ましいものは、R1が炭素原子数15の飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−ペンタデシルベンゼン(C15:0)が挙げられる。
AR17として特に好ましいものは、R1が炭素原子数17の飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−ヘプタデシルベンゼン(C17:0)が挙げられる。
AR19として特に好ましいものは、R1が炭素原子数19の飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−ノナデシルベンゼン(C19:0)が挙げられる。
AR21として特に好ましいものは、R1が炭素原子数21の飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−ヘンイコシルベンゼン(C21:0)が挙げられる。
AR23として特に好ましいものは、R1が炭素原子数23の飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−トリコシルベンゼン(C23:0)が挙げられる。
AR25として特に好ましいものは、R1が炭素原子数25飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−ペンタコシルベンゼン(C25:0)が挙げられる。
Particularly preferred as AR15 is one in which R 1 is a saturated alkyl group having 15 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-pentadecylbenzene (C15 : 0).
Particularly preferred as AR17 is one in which R 1 is a saturated alkyl group having 17 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-heptadecylbenzene (C17 : 0).
Particularly preferred as AR19 is one in which R 1 is a saturated alkyl group having 19 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-nonadecylbenzene (C19 : 0).
Particularly preferred as AR21 is one in which R 1 is a saturated alkyl group having 21 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-henecosylbenzene ( C21: 0).
Particularly preferred as AR23 is one in which R 1 is a saturated alkyl group having 23 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-tricosylbenzene (C23 : 0).
Particularly preferred as AR25 is one in which R 1 is a saturated alkyl group having 25 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-pentacosylbenzene (C25 : 0).
本発明のイネ科植物抽出物において、AR15、AR17、AR19、AR21、AR23及びAR25の含有量は、腸内フローラ調整能の一層の向上の観点から、それぞれ、下記範囲内にあることが好ましい。
AR15の含有量は、本発明のイネ科植物抽出物中、好ましくは0.1〜10.0質量%、更に好ましくは0.1〜5.0質量%、特に好ましくは0.5〜1.5質量%である。
AR17の含有量は、本発明のイネ科植物抽出物中、好ましくは1.0〜20.0質量%、更に好ましくは5.0〜15.0質量%、特に好ましくは8.0〜12.0質量%である。
AR19の含有量は、本発明のイネ科植物抽出物中、好ましくは25.0〜40.0質量%、更に好ましくは27.5〜37.5質量%、特に好ましくは30.0〜35.0質量%である。
AR21の含有量は、本発明のイネ科植物抽出物中、好ましくは40.0〜55.0質量%、更に好ましくは42.5〜52.5質量%、特に好ましくは45.0〜50.0質量%である。
AR23の含有量は、本発明のイネ科植物抽出物中、好ましくは1.0〜15.0質量%、更に好ましくは2.5〜12.5質量%、特に好ましくは5.0〜10.0質量%である。
AR25の含有量は、本発明のイネ科植物抽出物中、好ましくは0〜5.0質量%、更に好ましくは0〜2.0質量%、特に好ましくは0〜1.5質量%である。
In the gramineous plant extract of the present invention, the contents of AR15, AR17, AR19, AR21, AR23, and AR25 are each preferably within the following ranges from the viewpoint of further improving the ability to adjust intestinal flora.
The content of AR15 is preferably 0.1 to 10.0% by mass, more preferably 0.1 to 5.0% by mass, and particularly preferably 0.5 to 1.% by mass in the grass plant extract of the present invention. 5% by mass.
The content of AR17 is preferably 1.0 to 20.0% by mass, more preferably 5.0 to 15.0% by mass, and particularly preferably 8.0 to 12% in the grass plant extract of the present invention. 0% by mass.
The content of AR19 is preferably 25.0 to 40.0% by mass, more preferably 27.5 to 37.5% by mass, and particularly preferably 30.0 to 35.% in the grass plant extract of the present invention. 0% by mass.
The content of AR21 is preferably 40.0 to 55.0% by mass, more preferably 42.5 to 52.5% by mass, and particularly preferably 45.0 to 50.% in the grass plant extract of the present invention. 0% by mass.
The content of AR23 is preferably 1.0 to 15.0% by mass, more preferably 2.5 to 12.5% by mass, and particularly preferably 5.0 to 10% by mass in the grass plant extract of the present invention. 0% by mass.
The content of AR25 is preferably 0 to 5.0% by mass, more preferably 0 to 2.0% by mass, and particularly preferably 0 to 1.5% by mass in the grass plant extract of the present invention.
本発明のイネ科植物抽出物は、AR15、AR17、AR19、AR21、AR23及びAR25以外の他のアルキルレゾルシノールの1種以上を含有していても良い。この他のアルキルレゾルシノールとしては、例えば、前記一般式(I)におけるR1が炭素原子数27の飽和又は不飽和のアルキル基であるアルキルレゾルシノール(以下、AR27ともいう)が挙げられる。AR27として特に好ましいものは、R1が炭素原子数27の飽和アルキル基、R2が水素原子であるものであり、具体的には、1,3−ジヒドロキシ−5−n−ヘプタコシルベンゼン(C27:0)が挙げられる。 The grass plant extract of the present invention may contain one or more alkylresorcinols other than AR15, AR17, AR19, AR21, AR23, and AR25. Examples of the other alkylresorcinol include alkylresorcinol (hereinafter, also referred to as AR27) in which R 1 in the general formula (I) is a saturated or unsaturated alkyl group having 27 carbon atoms. Particularly preferred as AR27 is one in which R 1 is a saturated alkyl group having 27 carbon atoms and R 2 is a hydrogen atom. Specifically, 1,3-dihydroxy-5-n-heptacosylbenzene ( C27: 0).
本発明のイネ科植物抽出物は、腸内フローラ調整能を有するアルキルレゾルシノールの含有率が高いことが好ましく、斯かる観点から、イネ科植物からアルコールを用いて抽出された抽出物は、分配クロマトグラフィー等によって精製する、あるいは常法により濃縮・蒸発乾固することが好ましい。イネ科植物のアルコール抽出物の精製に用いる分配クロマトグラフィーとしては、例えば、移動相として非水系溶媒を用いる順相クロマトグラフィー法が挙げられ、オープンカラム法、中圧カラム法、高速液体クロマトグラフィー等の公知の方法を適宜選択することができる。 The grass plant extract of the present invention preferably has a high content of alkylresorcinol having an intestinal flora-controlling ability. From this point of view, an extract extracted from a grass plant using alcohol is a partition chromatography. It is preferable to purify by chromatography or to concentrate and evaporate to dryness by a conventional method. Examples of partition chromatography used to purify the alcoholic extract of Gramineae include normal phase chromatography using a non-aqueous solvent as the mobile phase, such as open column method, medium pressure column method, high performance liquid chromatography, etc. These known methods can be appropriately selected.
イネ科植物のアルコール抽出物の分配クロマトグラフィーにおける移動相としては、メタノール、エタノール、n−プロパノール、イソプロパノール、n−ブタノール等の1価の低級アルコール(好ましくは炭素原子数1〜4のもの)、及び1,3−ブチレングリコール、プロピレングリコール、グリセリン等の多価アルコール等の室温(25℃)で液体であるアルコール;ジエチルエーテル、プロピルエーテル等のエーテル;酢酸ブチル、酢酸エチル等のエステル;アセトン、エチルメチルケトン等のケトン;ヘキサン;塩化メチレン;アセトニトリル;並びにクロロホルム等が挙げられ、これら溶媒の1種を単独で又は2種以上を組み合わせて用いることができる。複数の溶媒を組み合わせて移動相とする場合、分配クロマトグラフィーの実施中(イネ科植物のアルコール抽出物の精製中)において、複数の溶媒の混合比を一定にするイソクラクティックモードでも良く、あるいは該混合比を変化させるグラジエントモードでも良い。また、分配クロマトグラフィーにおける担体としては、目的とする有効成分を担持−放出できる担体であればいずれも用いることができるが、一般的にはシリカゲル、ポリアクリルアミドゲル、デキストランゲル等を挙げることができる。イネ科植物のアルコール抽出物の分配クロマトグラフィーにおける検出波長は、170〜320nmであれば良く、好ましくは190〜280nmである。 As a mobile phase in partition chromatography of an alcoholic extract of a grass family, monovalent lower alcohols (preferably having 1 to 4 carbon atoms) such as methanol, ethanol, n-propanol, isopropanol, n-butanol, And alcohols that are liquid at room temperature (25 ° C.) such as polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin; ethers such as diethyl ether and propyl ether; esters such as butyl acetate and ethyl acetate; Examples include ketones such as ethyl methyl ketone; hexane; methylene chloride; acetonitrile; and chloroform. One of these solvents can be used alone, or two or more can be used in combination. When a plurality of solvents are combined to form a mobile phase, an isocratic mode in which the mixing ratio of the plurality of solvents is kept constant during partition chromatography (purification of the gramineous alcohol extract), or A gradient mode in which the mixing ratio is changed may be used. Any carrier can be used as the carrier in the partition chromatography as long as it can carry and release the target active ingredient, and generally includes silica gel, polyacrylamide gel, dextran gel and the like. . The detection wavelength in the partition chromatography of the alcoholic extract of the gramineous plant should just be 170-320 nm, Preferably it is 190-280 nm.
腸内フローラ調整能を有する本発明のイネ科植物抽出物は、特に、生体への悪影響が報告されている悪玉菌であるバクトロイデス属又はエンテロコッカス属の細菌に対して作用し、両細菌の一方又は両方の細菌数の、腸内の総菌数に占める割合を調整する作用を有する。より具体的には、本発明のイネ科植物抽出物は、i)高脂肪食の摂取などに起因して減少したバクテロイデス属の細菌の、腸内の総菌数に占める割合を増加させ、及び/又は、ii)高脂肪食の摂取などに起因して増加したエンテロコッカス属の細菌の、腸内の総菌数に占める割合を減少させ、結果として、高脂肪食の摂取などに起因する腸内フローラ構成の乱れを抑制し、健常時の腸内フローラ構成を維持し得る。 The gramineous plant extract of the present invention having the ability to adjust intestinal flora particularly acts on bacteria of the genus Bactoroides or Enterococcus, which are bad bacteria that have been reported to have adverse effects on living organisms, and one or both of these bacteria It has the effect of adjusting the ratio of the number of both bacteria to the total number of bacteria in the intestine. More specifically, the gramineous plant extract of the present invention increases i) the proportion of bacteria of the genus Bacteroides that have decreased due to ingestion of a high fat diet, etc., to the total number of bacteria in the intestine, and / Or ii) reducing the proportion of enterococcus bacteria that have increased due to the intake of a high fat diet to the total number of bacteria in the intestine, resulting in the The disturbance of the flora configuration can be suppressed, and the normal intestinal flora configuration can be maintained.
本発明のイネ科植物抽出物は、蛋白質を含んでいないか又は蛋白質を含んでいてもその含有量が比較的少ない、低蛋白なものである。特に、抽出源であるイネ科植物が小麦ふすまである場合、それから抽出されたイネ科植物抽出物は、蛋白質の含有量が非常に少ない低蛋白性である。本発明のイネ科植物抽出物における蛋白質の含有量は、抽出源であるイネ科植物の種類等にもよるが、本発明のイネ科植物抽出物中、好ましくは5質量%以下、更に好ましくは2質量%以下である。本発明のイネ科植物抽出物は低蛋白であるため、蛋白質の摂取量を制限する必要がある腎臓疾患患者等にも好適である。 The Gramineae plant extract of the present invention does not contain a protein or has a relatively low content even if it contains a protein, and has a low protein content. In particular, when the Gramineae plant that is the source of extraction is even wheat bran, the Gramineae plant extract extracted therefrom has a low protein content with a very low protein content. The content of the protein in the gramineous plant extract of the present invention depends on the kind of gramineous plant as the extraction source, but is preferably 5% by mass or less, more preferably in the gramineous plant extract of the present invention. 2% by mass or less. Since the gramineous plant extract of the present invention is low in protein, it is also suitable for patients with kidney diseases and the like who need to limit the intake of protein.
本発明のイネ科植物抽出物は、その腸内フローラ調整能を活かし、ヒト又は動物用の医薬品、飲食品、飼料等として、あるいはそれらを製造するために使用することができる。本発明のイネ科植物抽出物の形態は特に制限されず、例えば、イネ科植物のアルコール抽出物(前記一般式(I)で表されるアルキルレゾルシノール)を含む液状物(液体又は半液体)、該液状物中の液媒体(アルコール又は含水アルコール)を蒸発乾固して得られる乾固物又はその粉末、該乾固物又はその粉末をエタノール等のアルコールに溶解してなるアルコール溶液等が挙げられる。本発明はまた、前記本発明のイネ科植物抽出物を含有する医薬品、飲食品及び飼料を提供する。 The grass plant extract of the present invention can be used as a medicine for humans or animals, foods and drinks, feeds, etc., or for producing them, making use of its ability to adjust intestinal flora. The form of the grass plant extract of the present invention is not particularly limited. For example, a liquid material (liquid or semi-liquid) containing a grass plant alcohol extract (alkyl resorcinol represented by the general formula (I)), Examples include a dry solid obtained by evaporating and drying a liquid medium (alcohol or hydrous alcohol) in the liquid or a powder thereof, an alcohol solution obtained by dissolving the dry solid or the powder in an alcohol such as ethanol, and the like. It is done. The present invention also provides a pharmaceutical, a food and drink, and a feed containing the grass plant extract of the present invention.
本発明の医薬品、即ち腸内フローラ調整剤は、前記本発明のイネ科植物抽出物を有効成分として含有する腸内フローラ調整剤(整腸剤)であり得る。また、本発明の医薬品は、経口用の任意の剤型で投与され得る。経口投与のための剤型としては、錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤のような固形製剤、あるいはエリキシロール、シロップ及び懸濁液のような液体製剤が挙げられる。 The pharmaceutical product of the present invention, that is, the intestinal flora adjusting agent, may be an intestinal flora adjusting agent (intestinal regulating agent) containing the grass plant extract of the present invention as an active ingredient. The pharmaceutical agent of the present invention can be administered in any oral dosage form. Dosage forms for oral administration include solid preparations such as tablets, coated tablets, granules, powders, capsules, or liquid preparations such as elixirol, syrups and suspensions.
本発明の飲食品又は飼料は、前記本発明のイネ科植物抽出物を有効成分として含有し、且つ腸内フローラ調整効果を企図して、その旨を表示した機能性飲食品、病者用飲食品、特定保健用飲食品、家畜用飼料、ペットフード等であり得る。本発明の飲食品又は飼料の形態は、特に限定されないが、例えば、飲料の形態としては、茶飲料、コーヒー飲料、乳飲料、果汁飲料、炭酸飲料、アルコール飲料、清涼飲料等が挙げられ、食品又は飼料の形態としては、固形、半固形又は液状であり得、錠剤形態、丸剤形態、カプセル形態、液剤形態、シロップ形態、粉末形態、顆粒形態等が挙げられる。具体的な食品の形態としては、パン類、麺類、ゼリー状食品や各種スナック類、焼き菓子、ケーキ類、チョコレート、ガム、飴、タブレット、カプセル、スープ類、乳製品、冷凍食品、インスタント食品、サプリメント、その他加工食品、調味料及びそれらの材料等が挙げられる。 The food / beverage product or feed of the present invention contains the grass plant extract of the present invention as an active ingredient, and is intended to have an intestinal flora adjusting effect, and a functional food / beverage product or food / beverage for the sick is displayed. Product, food and drink for specified health use, livestock feed, pet food and the like. The form of the food or drink or feed of the present invention is not particularly limited, and examples of the form of the beverage include tea drinks, coffee drinks, milk drinks, fruit drinks, carbonated drinks, alcoholic drinks, soft drinks, and the like. Alternatively, the form of the feed can be solid, semi-solid or liquid, and includes tablet form, pill form, capsule form, liquid form, syrup form, powder form, granule form and the like. Specific food forms include breads, noodles, jelly-like foods and various snacks, baked goods, cakes, chocolate, gum, rice cakes, tablets, capsules, soups, dairy products, frozen foods, instant foods, Examples include supplements, other processed foods, seasonings, and materials thereof.
本発明の医薬品、飲食品又は飼料は、必要に応じて、前記本発明のイネ科植物抽出物(前記一般式(I)で表されるアルキルレゾルシノール)以外の他の成分、例えば、他の有効成分及び/又は通常利用される添加物若しくは担体を含有していても良い。
医薬品の場合、前記他の成分としては、例えば、他の薬効成分、美容成分、栄養成分、ならびに賦形剤、崩壊剤、結合剤、滑沢剤、界面活性剤、水溶性高分子、希釈剤、浸透圧調整剤、pH調整剤、乳化剤、防腐剤、緩衝剤、安定化剤、酸化防止剤、増粘剤、紫外線吸収剤、活性増強剤、着色剤、甘味料、矯味剤、矯臭剤、酸味料等が挙げられ、これらの1種を単独で又は2種以上を組み合わせて用いることができる。
飲食品又は飼料の場合、前記他の成分としては、例えば、他の飲食品材料、栄養成分、美容成分、他の機能性素材ならびに溶剤、油、軟化剤、乳化剤、防腐剤、安定剤、酸化防止剤、着色剤、保湿剤、増粘剤、光沢剤、甘味料、香料等の添加物等が挙げられ、これらの1種を単独で又は2種以上を組み合わせて用いることができる。
The pharmaceutical, food and drink, or feed of the present invention may contain other ingredients other than the grass plant extract of the present invention (alkylresorcinol represented by the general formula (I)), for example, other effective, as necessary. It may contain components and / or commonly used additives or carriers.
In the case of pharmaceuticals, examples of the other ingredients include other medicinal ingredients, cosmetic ingredients, nutrition ingredients, and excipients, disintegrants, binders, lubricants, surfactants, water-soluble polymers, and diluents. , Osmotic pressure adjusting agent, pH adjusting agent, emulsifier, preservative, buffer, stabilizer, antioxidant, thickener, ultraviolet absorber, activity enhancer, colorant, sweetener, flavoring agent, flavoring agent, A sour agent etc. are mentioned, These 1 type can be used individually or in combination of 2 or more types.
In the case of food and drink or feed, the other ingredients include, for example, other food and drink materials, nutritional ingredients, cosmetic ingredients, other functional materials and solvents, oils, softeners, emulsifiers, preservatives, stabilizers, oxidation Examples thereof include additives such as an inhibitor, a colorant, a humectant, a thickener, a brightener, a sweetener, and a fragrance, and these can be used alone or in combination of two or more.
本発明の医薬品、飲食品又は飼料における前記本発明のイネ科植物抽出物(前記一般式(I)で表されるアルキルレゾルシノール)の摂取量は、それらの剤型や形態により異なるが、医薬品、飲食品および飼料のいずれの場合も一日あたり0.01g〜10gとなるように摂取することが好ましい。 The intake of the grass plant extract of the present invention (alkylresorcinol represented by the general formula (I)) in the pharmaceutical, food and drink of the present invention varies depending on their dosage form and form, In any case of food and drink and feed, it is preferably ingested so as to be 0.01 to 10 g per day.
以下、実施例及び試験例を挙げて、本発明を更に詳細に説明するが、本発明はこれらの実施例及び試験例により制限されるものではない。 EXAMPLES Hereinafter, although an Example and a test example are given and this invention is demonstrated further in detail, this invention is not restrict | limited by these Examples and a test example.
〔実施例〕
下記<抽出精製法>により、前記一般式(I)で表されるアルキルレゾルシノールを含有するイネ科植物抽出物(小麦抽出物)を得た。このイネ科植物抽出物の組成は次の通り。
・1,3−ジヒドロキシ−5−n−ペンタデシルベンゼン(C15:0)1.2質量%。
・1,3−ジヒドロキシ−5−n−ヘプタデシルベンゼン(C17:0)10.9質量%。
・1,3−ジヒドロキシ−5−n−ノナデシルベンゼン(C19:0)33.9質量%。
・1,3−ジヒドロキシ−5−n−ヘンイコシルベンゼン(C21:0)46.4質量%。
・1,3−ジヒドロキシ−5−n−トリコシルベンゼン(C23:0)7.5質量%。
・1,3−ジヒドロキシ−5−n−ペンタコシルベンゼン(C25:0)0.1質量%。
〔Example〕
By the following <Extraction and purification method>, a Gramineae plant extract (wheat extract) containing an alkylresorcinol represented by the general formula (I) was obtained. The composition of this grass plant extract is as follows.
-1,3-dihydroxy-5-n-pentadecylbenzene (C15: 0) 1.2 mass%.
-1,3-dihydroxy-5-n-heptadecylbenzene (C17: 0) 10.9 mass%.
-1,3-dihydroxy-5-n-nonadecylbenzene (C19: 0) 33.9 mass%.
-1,3-dihydroxy-5-n-henicosylbenzene (C21: 0) 46.4 mass%.
-7.5 mass% of 1, 3- dihydroxy-5-n-tricosyl benzene (C23: 0).
-1,3-dihydroxy-5-n-pentacosylbenzene (C25: 0) 0.1 mass%.
<抽出精製法>
小麦ふすまに質量で5倍量のエタノールを添加して、600rpm、室温の条件で、16時間撹拌抽出した。抽出物を濾過して不要物を除きエタノール抽出液を回収した後、エタノールを留去し、小麦ふすまのエタノール抽出物を得た。次いで、このエタノール抽出物を中圧クロマトグラフィーによって精製した。中圧クロマトグラフィー条件は下記の通りである。溶出開始後31〜36分に出現するピーク成分を回収して、溶媒留去し、前記一般式(I)で表されるアルキルレゾルシノールを含有するイネ科植物抽出物を得た。
(中圧クロマトグラフィーの条件)
・カラム:シリカゲル(インジェクトカラム3L、ハイフラッシュカラム5L、60Å、40μm、山善株式会社製)
・移動相:ヘキサン/酢酸エチル混合溶媒(体積比)=90/10にて9分、80/20にて15分、60/40にて16分
・検出波長:254nm
<Extraction purification method>
Ethanol in an amount of 5 times by mass was added to wheat bran, and the mixture was extracted by stirring for 16 hours under conditions of 600 rpm and room temperature. The extract was filtered to remove unnecessary substances and an ethanol extract was collected, and then ethanol was distilled off to obtain an ethanol extract of wheat bran. The ethanol extract was then purified by medium pressure chromatography. Medium pressure chromatography conditions are as follows. A peak component appearing 31 to 36 minutes after the start of elution was collected and the solvent was distilled off to obtain a grass plant extract containing the alkylresorcinol represented by the general formula (I).
(Medium pressure chromatography conditions)
Column: silica gel (injection column 3 L, high flash column 5 L, 60 mm, 40 μm, manufactured by Yamazen Corporation)
・ Mobile phase: Hexane / ethyl acetate mixed solvent (volume ratio) = 9/10 at 90/10, 15 minutes at 80/20, 16 minutes at 60/40 ・ Detection wavelength: 254 nm
尚、前記<抽出精製法>における小麦ふすまのエタノール抽出物の精製は、中圧クロマトグラフィーに代えて、HPLCによって行うこともできる。その場合、エタノール抽出物にメタノールを添加して該エタノール抽出物の濃度が200ug/mlのメタノール添加液を調製し、該メタノール添加液を、孔径0.45μmのフィルターを通過させ、その通過分を、HPLCの試料とする。HPLCの条件は下記の通り。
(HPLCの条件)
・カラム:シリカゲル(ODS−80A、5μm、4.6×250mm、ジーエルサイエンス株式会社製)
・ガードカラム:ODS−80A、5μm、4.6×50mm、
・カラム温度:30℃
・移動相:メタノール100%
・検出波長:215nm
In addition, the purification of the wheat bran ethanol extract in the <Extraction and purification method> can be performed by HPLC instead of medium pressure chromatography. In that case, methanol is added to the ethanol extract to prepare a methanol addition solution having a concentration of 200 ug / ml, and the methanol addition solution is passed through a filter having a pore size of 0.45 μm. , HPLC sample. HPLC conditions are as follows.
(HPLC conditions)
Column: silica gel (ODS-80A, 5 μm, 4.6 × 250 mm, manufactured by GL Sciences Inc.)
Guard column: ODS-80A, 5 μm, 4.6 × 50 mm,
-Column temperature: 30 ° C
-Mobile phase: 100% methanol
・ Detection wavelength: 215 nm
〔試験例〕
実施例のイネ科植物抽出物について、下記試験により、高脂肪高ショ糖食負荷マウスの腸内フローラへの影響を調べた。その結果を図1及び図2に示す。図1及び図2中、NDは、普通食を摂餌したマウス群、HFHSDは、高脂肪高ショ糖食を摂餌したマウス群、HFHSDARは、実施例のイネ科植物抽出物が添加された高脂肪高ショ糖食を摂餌したマウス群である。
[Test example]
About the gramineous plant extract of an Example, the influence on the intestinal flora of a high fat high sucrose diet load mouse | mouth was investigated by the following test. The results are shown in FIGS. 1 and 2, ND is a group of mice fed a normal diet, HFHSD is a group of mice fed a high-fat high sucrose diet, and HFHSDAR is added with the grass plant extract of the example. A group of mice fed a high fat, high sucrose diet.
<腸内フローラ調整作用確認試験>
普通食(ND)として、AIN93M(ミルクカゼイン使用)(オリエンタル酵母工業株式会社製)、高脂肪高ショ糖食(HFHSD)として、F2HFHSD(オリエンタル酵母工業株式会社製)を用意し、また別途、HFHSDに実施例のイネ科植物抽出物を0.5質量%添加したもの(HFHSDAR)を用意した。C57BL/6JJmsSlc系統のマウス(4週齢の雄性、日本エスエルシー株式会社)を明期12時間、暗期12時間の明暗サイクル下(0:00点灯、12:00消灯)で2週間馴化飼育した後、これらのマウスをND摂餌群(全6ゲージで各ゲージ2匹)と、HFHSD摂餌群(全6ゲージで各ゲージ2匹)と、HFHSDAR摂餌群(全6ゲージで各ゲージ2匹)との3群に分け、10週間自由摂食させた。その自由摂食期間後、各ゲージ中の1日分の全糞便を回収した。回収した糞便20mgを50mLのPBSに加えて懸濁させ、その懸濁液を14000×gで10分間遠心し、その上清を除去する。この懸濁液の遠心及び上清の除去操作を3回繰り返して得られた残渣に、250μLのLysis bufferに懸濁させる。このLysis bufferは、500mMのNaClと、50mMのTris−HCl(pH8.0)と、50mMのEDTAと、4%のSDSとを混合して調製したものである。さらに懸濁液に、100mgの直径0.1mmのグラスビーズとTE飽和フェノール500μLとを加え、ホモゲナイザー((株)トミー精工製、Micro Smash MS-100R)を用いて4500rpmで30秒間ホモゲナイズした後、該懸濁液を20000×gで5分間遠心し、その上清を回収した。回収した上清を、フェノール:クロロホルム:イソアミルアルコール=25:24:1の含有体積比を持つ混合液に添加後、該混合液にイソプロパノールを加えて該混合液中のDNAを沈殿させ、その沈殿物を回収した。回収した沈殿物(DNA)を、50μLのTE bufferに溶解させ、NanoDrop 2000c(Thermo Scientific)で定量PCR法によりDNA濃度を測定した。定量PCR法には、SYBR(登録商標)Premix Ex TaqTM II(タカラバイオ株式会社製)とLightCyclerTM とを用い、95℃10秒及び95℃5秒(変性)に続いて57℃10秒(アニーリング)と72℃20秒(伸長ステップ)とを行うサイクルを45回繰り返した。プライマーは以下の配列のものを用いた。
・All bacteria: Forward;CCTACGGGAGGCAGCAG、Reverse;ATTACCGCGGCTGCTGG
・Bacteroides/Prevotella/Porphyromonas: Forward;GGTGTCGGCTTAAGTGCCAT、Reverse;CGGAYGTAAGGGCCGTGC
・Enterococcus sp.: Forward;CCCTTATTGTTAGTTGCCATCATT、Reverse;ACTCGTTGTACTTCCCATTGT
相対定量法にてリアルタイムPCRを実施し、その結果を用いてAll bacteriaと目的遺伝子との比を算出した。相対定量法を下記に述べる。任意のプールしたDNAサンプルを希釈し、それらをテンプレートにしてAll bacteria、Bacteroides/Prevotella/Porphyromonas、及びEnterococcus sp.の3対のプライマーセットでそれぞれリアルタイムPCRを実施し、プライマーセットごとの検量線を作成した。そして、マウスの糞中DNAを同量用いて3対のプライマーでそれぞれリアルタイムPCRを実施した。それぞれのCt値から検量線を元にそれぞれの相対値を求めた。
<Intestinal flora adjusting action confirmation test>
As a normal diet (ND), AIN93M (using milk casein) (made by Oriental Yeast Co., Ltd.) and F2HFHSD (made by Oriental Yeast Industry Co., Ltd.) as a high fat high sucrose diet (HFHSD) are prepared. Prepared by adding 0.5% by mass of the gramineous plant extract of Example (HFHSDAR) was prepared. C57BL / 6JJmsSlc strain mice (4-week-old male, Japan SLC Co., Ltd.) were bred for 2 weeks under a light-dark cycle of 12 hours light and 12 hours dark (lights on at 0:00, lights off at 12:00). Later, these mice were divided into ND feeding group (2 gauges each with 6 gauges), HFHSD feeding group (2 gauges each with 6 gauges), and HFHSDAR feeding group (2 gauges with 6 gauges each). And were allowed to eat freely for 10 weeks. After the free feeding period, one day of total feces in each gauge was collected. The collected feces (20 mg) is suspended in 50 mL of PBS, and the suspension is centrifuged at 14000 × g for 10 minutes, and the supernatant is removed. The suspension obtained by centrifuging the suspension and removing the supernatant three times is suspended in 250 μL of lysis buffer. This Lysis buffer is prepared by mixing 500 mM NaCl, 50 mM Tris-HCl (pH 8.0), 50 mM EDTA, and 4% SDS. Further, 100 mg of glass beads having a diameter of 0.1 mm and TE saturated phenol 500 μL were added to the suspension, and homogenized at 4500 rpm for 30 seconds using a homogenizer (Micro Smash MS-100R, manufactured by Tommy Seiko Co., Ltd.) The suspension was centrifuged at 20000 × g for 5 minutes, and the supernatant was collected. The collected supernatant is added to a mixed solution having a content volume ratio of phenol: chloroform: isoamyl alcohol = 25: 24: 1, and then isopropanol is added to the mixed solution to precipitate DNA in the mixed solution. The material was collected. The collected precipitate (DNA) was dissolved in 50 μL of TE buffer, and the DNA concentration was measured by a quantitative PCR method using NanoDrop 2000c (Thermo Scientific). For the quantitative PCR method, SYBR (registered trademark) Premix Ex Taq ™ II (manufactured by Takara Bio Inc.) and LightCycler T M were used, followed by 95 ° C. for 10 seconds and 95 ° C. for 5 seconds (denaturation), followed by 57 ° C. for 10 seconds. The cycle of performing (annealing) and 72 ° C. for 20 seconds (extension step) was repeated 45 times. Primers having the following sequences were used.
・ All bacteria: Forward; CCTACGGGAGGCAGCAG, Reverse; ATTACCGCGGCTGCTGG
・ Bacteroides / Prevotella / Porphyromonas: Forward; GGTGTCGGCTTAAGTGCCAT, Reverse; CGGAYGTAAGGGCCGTGC
・ Enterococcus sp .: Forward; CCCTTATTGTTAGTTGCCATCATT, Reverse; ACTCGTTGTACTTCCCATTGT
Real-time PCR was performed by the relative quantification method, and the ratio between All bacteria and the target gene was calculated using the results. The relative quantification method is described below. Dilute any pooled DNA sample and use them as a template to perform real-time PCR with all three primer sets of All bacteria, Bacteroides / Prevotella / Porphyromonas, and Enterococcus sp. To create a calibration curve for each primer set did. Then, real-time PCR was carried out with 3 pairs of primers using the same amount of mouse feces DNA. Each relative value was calculated | required based on the calibration curve from each Ct value.
図1は、腸内フローラ調整作用確認試験における、各マウス群の糞便中のバクトロイデス属の相対値をAll bacteriaの相対値で割ったグラフである。図1中、ND(普通食摂餌群)は、平均値1.05、標準誤差0.09であり、HFHSD(高脂肪高ショ糖食摂餌群)は、平均値0.65、標準誤差0.08であり、HFHSDAR(実施例のイネ科植物抽出物が添加された高脂肪高ショ糖食摂餌群)は、平均値0.87、標準誤差0.10であった。
図2は、同試験における、各マウス群の糞便中のエンテロコッカス属の相対値をAll bacteriaの相対値で割ったグラフであり、図2中、NDは、平均値0.40、標準誤差0.06であり、HFHSDは、平均値2.45、標準誤差0.48あり、HFHSDARは、平均値0.89、標準誤差0.16であった。
FIG. 1 is a graph obtained by dividing the relative value of the genus Bacteroides in the stool of each mouse group by the relative value of All bacteria in the intestinal flora adjusting action confirmation test. In FIG. 1, ND (ordinary diet feeding group) has an average value of 1.05 and a standard error of 0.09, and HFHSD (high fat high sucrose diet feeding group) has an average value of 0.65 and a standard error. The average value of the HFHSDAR (high fat high sucrose diet group to which the grass plant extract of Example was added) was 0.87 and the standard error was 0.10.
FIG. 2 is a graph obtained by dividing the relative value of Enterococcus in the stool of each mouse group by the relative value of All bacteria in the same test. In FIG. 06, HFHSD had an average value of 2.45 and a standard error of 0.48, and HFHSDAR had an average value of 0.89 and a standard error of 0.16.
図1によれば、HFHSD摂餌群の糞便中のバクテロイデス属の相対的細菌数がND摂餌群のそれに比べて有意に減少していることから、HFHSDの継続的な摂取がバクテロイデス属の相対的細菌数の減少を引き起こすことが明らかである。これは、HFHSDとして用いたF2HFHSDに、NDとして用いたAIN93Mには含まれていない牛脂及びラードが含まれていることに起因するものと推察される。これに対し、HFHSDAR摂餌群の糞便中のバクテロイデス属の相対的細菌数はHFHSD摂餌群のそれに比べて有意に増加しており、ND摂餌群のそれに近いことから、HFHSDARに含まれる実施例のイネ科植物抽出物が、バクテロイデス属の相対的細菌数を、HFHSDの継続的な摂取前の健常時における相対的細菌数に近づける作用を有することが明らかである。 According to FIG. 1, since the relative number of Bacteroides bacteria in the stool of the HFHSD fed group is significantly reduced compared to that of the ND fed group, the continuous intake of HFHSD is relative to that of the Bacteroides genus. It is clear that it causes a decrease in the number of experimental bacteria. This is presumably because F2HFHSD used as HFHSD contains beef tallow and lard which are not included in AIN93M used as ND. In contrast, the relative number of bacteria of the genus Bacteroides in the stool of the HFHSDAR feeding group is significantly increased compared to that of the HFHSD feeding group, and is close to that of the ND feeding group. It is clear that the example Gramineae extract has the effect of bringing the relative bacterial count of the genus Bacteroides closer to the relative bacterial count at normal times prior to continued intake of HFHSD.
また図2によれば、HFHSD摂餌群の糞便中のエンテロコッカス属の相対的細菌数がND摂餌群のそれに比べて有意に増加していることから、HFHSDの継続的な摂取がエンテロコッカス属の相対的細菌数の増加を引き起こすことが明らかである。これは、HFHSDとして用いたF2HFHSDに、NDとして用いたAIN93Mには含まれていない牛脂及びラードが含まれていることに起因するものと推察される。これに対し、HFHSDAR摂餌群の糞便中のエンテロコッカス属の相対的細菌数はHFHSD摂餌群のそれに比べて有意に減少しており、ND摂餌群のそれに近いことから、HFHSDARに含まれる実施例のイネ科植物抽出物が、エンテロコッカス属の相対的細菌数を、HFHSDの継続的な摂取前の健常時における相対的細菌数に近づける作用を有することが明らかである。 Moreover, according to FIG. 2, since the relative number of bacteria of the genus Enterococcus in the stool of the HFHSD feeding group is significantly increased compared to that of the ND feeding group, the continuous intake of HFHSD is It is clear that it causes an increase in the relative bacterial count. This is presumably because F2HFHSD used as HFHSD contains beef tallow and lard which are not included in AIN93M used as ND. On the other hand, the relative bacterial count of Enterococcus in the feces of the HFHSDAR feeding group is significantly reduced compared to that of the HFHSD feeding group, and is close to that of the ND feeding group. It is clear that the example Gramineae extract has the effect of bringing the relative bacterial count of the genus Enterococcus closer to the relative bacterial count in healthy before continuous intake of HFHSD.
以上の結果から、実施例のイネ科植物抽出物は、腸内フローラ調整能、即ち、高脂肪食の摂取に起因する腸内フローラ構成の変化を抑制し、健常時の腸内フローラ構成を維持し得る作用を有することが明らかである。 From the above results, the gramineous plant extract of the example suppresses changes in the intestinal flora configuration due to intestinal flora adjustment ability, that is, intake of a high fat diet, and maintains a normal intestinal flora configuration It is clear that it has a possible action.
<腸内フローラ調整作用確認試験>
普通食(ND)として、AIN93M(ミルクカゼイン使用)(オリエンタル酵母工業株式会社製)、高脂肪高ショ糖食(HFHSD)として、F2HFHSD(オリエンタル酵母工業株式会社製)を用意し、また別途、HFHSDに実施例のイネ科植物抽出物を0.5質量%添加したもの(HFHSDAR)を用意した。C57BL/6JJmsSlc系統のマウス(4週齢の雄性、日本エスエルシー株式会社)を明期12時間、暗期12時間の明暗サイクル下(0:00点灯、12:00消灯)で2週間馴化飼育した後、これらのマウスをND摂餌群(全6ゲージで各ゲージ2匹)と、HFHSD摂餌群(全6ゲージで各ゲージ2匹)と、HFHSDAR摂餌群(全6ゲージで各ゲージ2匹)との3群に分け、10週間自由摂食させた。その自由摂食期間後、各ゲージ中の1日分の全糞便を回収した。回収した糞便20mgを50mLのPBSに加えて懸濁させ、その懸濁液を14000×gで10分間遠心し、その上清を除去する。この懸濁液の遠心及び上清の除去操作を3回繰り返して得られた残渣に、250μLのLysis bufferに懸濁させる。このLysis bufferは、500mMのNaClと、50mMのTris−HCl(pH8.0)と、50mMのEDTAと、4%のSDSとを混合して調製したものである。さらに懸濁液に、100mgの直径0.1mmのグラスビーズとTE飽和フェノール500μLとを加え、ホモゲナイザー((株)トミー精工製、Micro Smash MS-100R)を用いて4500rpmで30秒間ホモゲナイズした後、該懸濁液を20000×gで5分間遠心し、その上清を回収した。回収した上清を、フェノール:クロロホルム:イソアミルアルコール=25:24:1の含有体積比を持つ混合液に添加後、該混合液にイソプロパノールを加えて該混合液中のDNAを沈殿させ、その沈殿物を回収した。回収した沈殿物(DNA)を、50μLのTE bufferに溶解させ、NanoDrop 2000c(Thermo Scientific)で定量PCR法によりDNA濃度を測定した。定量PCR法には、SYBR(登録商標)Premix Ex TaqTM II(タカラバイオ株式会社製)とLightCyclerTM とを用い、95℃10秒及び95℃5秒(変性)に続いて57℃10秒(アニーリング)と72℃20秒(伸長ステップ)とを行うサイクルを45回繰り返した。プライマーは、All bacteriaについては配列表の配列番号1(Forward)及び2(Reverse)に示すものを、Bacteroides/Prevotella/Porphyromonasについては配列表の配列番号3(Forward)及び4(Reverse)に示すものを、Enterococcus sp. については配列表の配列番号5(Forward)及び6(Reverse)に示すものをそれぞれ用いた。
相対定量法にてリアルタイムPCRを実施し、その結果を用いてAll bacteriaと目的遺伝子との比を算出した。相対定量法を下記に述べる。任意のプールしたDNAサンプルを希釈し、それらをテンプレートにしてAll bacteria、Bacteroides/Prevotella/Porphyromonas、及びEnterococcus sp.の3対のプライマーセットでそれぞれリアルタイムPCRを実施し、プライマーセットごとの検量線を作成した。そして、マウスの糞中DNAを同量用いて3対のプライマーでそれぞれリアルタイムPCRを実施した。それぞれのCt値から検量線を元にそれぞれの相対値を求めた。
<Intestinal flora adjusting action confirmation test>
As a normal diet (ND), AIN93M (using milk casein) (made by Oriental Yeast Co., Ltd.) and F2HFHSD (made by Oriental Yeast Industry Co., Ltd.) as a high fat high sucrose diet (HFHSD) are prepared. Prepared by adding 0.5% by mass of the gramineous plant extract of Example (HFHSDAR) was prepared. C57BL / 6JJmsSlc strain mice (4-week-old male, Japan SLC Co., Ltd.) were bred for 2 weeks under a light-dark cycle of 12 hours light and 12 hours dark (lights on at 0:00, lights off at 12:00). Later, these mice were divided into ND feeding group (2 gauges each with 6 gauges), HFHSD feeding group (2 gauges each with 6 gauges), and HFHSDAR feeding group (2 gauges with 6 gauges each). And were allowed to eat freely for 10 weeks. After the free feeding period, one day of total feces in each gauge was collected. The collected feces (20 mg) is suspended in 50 mL of PBS, and the suspension is centrifuged at 14000 × g for 10 minutes, and the supernatant is removed. The suspension obtained by centrifuging the suspension and removing the supernatant three times is suspended in 250 μL of lysis buffer. This Lysis buffer is prepared by mixing 500 mM NaCl, 50 mM Tris-HCl (pH 8.0), 50 mM EDTA, and 4% SDS. Further, 100 mg of glass beads having a diameter of 0.1 mm and TE saturated phenol 500 μL were added to the suspension, and homogenized at 4500 rpm for 30 seconds using a homogenizer (Micro Smash MS-100R, manufactured by Tommy Seiko Co., Ltd.) The suspension was centrifuged at 20000 × g for 5 minutes, and the supernatant was collected. The collected supernatant is added to a mixed solution having a content volume ratio of phenol: chloroform: isoamyl alcohol = 25: 24: 1, and then isopropanol is added to the mixed solution to precipitate DNA in the mixed solution. The material was collected. The collected precipitate (DNA) was dissolved in 50 μL of TE buffer, and the DNA concentration was measured by a quantitative PCR method using NanoDrop 2000c (Thermo Scientific). For the quantitative PCR method, SYBR (registered trademark) Premix Ex Taq ™ II (manufactured by Takara Bio Inc.) and LightCycler T M were used, followed by 95 ° C. for 10 seconds and 95 ° C. for 5 seconds (denaturation), followed by 57 ° C. for 10 seconds. The cycle of performing (annealing) and 72 ° C. for 20 seconds (extension step) was repeated 45 times. Primers are those shown in SEQ ID NO: 1 (Forward) and 2 (Reverse) in the sequence listing for All bacteria, and those shown in SEQ ID NO: 3 (Forward) and 4 (Reverse) in the sequence listing for Bacteroides / Prevotella / Porphyromonas. As for Enterococcus sp., Those shown in SEQ ID NO: 5 (Forward) and 6 (Reverse) in the sequence listing were used , respectively .
Real-time PCR was performed by the relative quantification method, and the ratio between All bacteria and the target gene was calculated using the results. The relative quantification method is described below. Dilute any pooled DNA sample and use them as a template to perform real-time PCR with all three primer sets of All bacteria, Bacteroides / Prevotella / Porphyromonas, and Enterococcus sp. To create a calibration curve for each primer set did. Then, real-time PCR was carried out with 3 pairs of primers using the same amount of mouse feces DNA. Each relative value was calculated | required based on the calibration curve from each Ct value.
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018052896A (en) * | 2016-09-30 | 2018-04-05 | 株式会社 先端医療開発 | Distribution ratio regulator of intestinal bacterial flora |
JP2019198281A (en) * | 2018-05-17 | 2019-11-21 | 花王株式会社 | Intestinal flora-improving food and drink |
WO2020235546A1 (en) | 2019-05-22 | 2020-11-26 | 日東富士製粉株式会社 | Composition for improving liver function |
WO2022032282A1 (en) * | 2020-08-06 | 2022-02-10 | Alfred E. Mann Institute For Biomedical Engineering At The University Of Southern California | Methods and reagents for microbiome analysis |
Citations (3)
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JP2002338484A (en) * | 2001-05-16 | 2002-11-27 | Tama Seikagaku Kk | Agent for lowering sugar absorption rate in small intestine and enteric bacteria activating agent containing wheat-originated protein |
JP2010285425A (en) * | 2009-05-12 | 2010-12-24 | Fujifilm Corp | Agent for regulating composition ratio of intestinal bacterial flora |
JP2014139166A (en) * | 2012-12-20 | 2014-07-31 | National Institute Of Advanced Industrial & Technology | Improvement agent for abnormal glucose tolerance |
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2014
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JP2002338484A (en) * | 2001-05-16 | 2002-11-27 | Tama Seikagaku Kk | Agent for lowering sugar absorption rate in small intestine and enteric bacteria activating agent containing wheat-originated protein |
JP2010285425A (en) * | 2009-05-12 | 2010-12-24 | Fujifilm Corp | Agent for regulating composition ratio of intestinal bacterial flora |
JP2014139166A (en) * | 2012-12-20 | 2014-07-31 | National Institute Of Advanced Industrial & Technology | Improvement agent for abnormal glucose tolerance |
Non-Patent Citations (2)
Title |
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PHARMACOGN. MAG., vol. 9, no. 36, JPN6017028259, 2013, pages 309 - 314, ISSN: 0003769966 * |
糖尿病, vol. Vol.48 Suppl.2, JPN6010027841, 2005, pages 266 - 105, ISSN: 0003769967 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018052896A (en) * | 2016-09-30 | 2018-04-05 | 株式会社 先端医療開発 | Distribution ratio regulator of intestinal bacterial flora |
JP2019198281A (en) * | 2018-05-17 | 2019-11-21 | 花王株式会社 | Intestinal flora-improving food and drink |
WO2020235546A1 (en) | 2019-05-22 | 2020-11-26 | 日東富士製粉株式会社 | Composition for improving liver function |
WO2022032282A1 (en) * | 2020-08-06 | 2022-02-10 | Alfred E. Mann Institute For Biomedical Engineering At The University Of Southern California | Methods and reagents for microbiome analysis |
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