JP6294153B2 - Composition for promoting GLP-1 production - Google Patents
Composition for promoting GLP-1 production Download PDFInfo
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- JP6294153B2 JP6294153B2 JP2014102928A JP2014102928A JP6294153B2 JP 6294153 B2 JP6294153 B2 JP 6294153B2 JP 2014102928 A JP2014102928 A JP 2014102928A JP 2014102928 A JP2014102928 A JP 2014102928A JP 6294153 B2 JP6294153 B2 JP 6294153B2
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- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 title claims description 47
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Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Description
本発明は、ＧＬＰ−１産生促進組成物およびその利用に関する。 The present invention relates to a composition for promoting GLP-1 production and use thereof.
消化管ホルモンの一種である、グルカゴン様ペプチド−１；glucagon-like peptide-1(以下、ＧＬＰ−１と略記する。）は近年その生理作用に注目が集まっている。
ＧＬＰ−１は、主として膵臓に作用し、β細胞のインスリン放出をグルコース濃度依存的に促進することが知られている。また、グルカゴンの分泌を抑制し、胃の空洞化を遅らせ、末梢のグルコース処理を高めると言われている。
Glucagon-like peptide-1 (hereinafter abbreviated as GLP-1), which is a kind of gastrointestinal hormone, has attracted attention in recent years for its physiological action.
GLP-1 is known to act mainly on the pancreas and promote β-cell insulin release in a glucose concentration-dependent manner. It is also said to suppress glucagon secretion, delay gastric cavitation, and enhance peripheral glucose processing.
ＧＬＰ−１の投与によりインスリン非依存型糖尿病患者において食後のグルコースレベルが正常化され得ることから、ＧＬＰ−１は糖尿病の治療薬としての可能性を有している。また、ＧＬＰ−１はインスリン依存型糖尿病患者において血糖コントロールを改善する作用も有していることが知られている。さらに、ＧＬＰ−１のインスリン放出促進作用は血漿グルコース濃度に依存しているため、低い血漿グルコース濃度ではインスリン放出が低いため、低血糖症を招かないメリットがある。このため、必要時に、血中ＧＬＰ−１量をコントロールすることによって、安全性の高い糖尿病治療が可能になるものと期待されている。 Since administration of GLP-1 can normalize postprandial glucose levels in non-insulin dependent diabetic patients, GLP-1 has potential as a therapeutic agent for diabetes. GLP-1 is also known to have an effect of improving glycemic control in insulin-dependent diabetic patients. Furthermore, since the insulin release promoting action of GLP-1 depends on the plasma glucose concentration, there is a merit that hypoglycemia does not occur because insulin release is low at a low plasma glucose concentration. For this reason, it is expected that highly safe treatment of diabetes will be possible by controlling the blood GLP-1 level when necessary.
血中ＧＬＰ−１量をコントロールする方法として、ＧＬＰ−１を直接経口又は注射剤として投与することができるが、ＧＬＰ−１は２〜６分と非常に短い血漿中半減期のため、その治療剤としての可能性が限定されているため、生体内でＧＬＰ−１を誘導する方法が検討されている。 As a method for controlling the amount of GLP-1 in the blood, GLP-1 can be administered directly orally or as an injection, but since GLP-1 has a very short plasma half-life of 2 to 6 minutes, its treatment Since the possibility as an agent is limited, a method for inducing GLP-1 in vivo has been studied.
ＧＬＰ−１産生あるいは分泌を誘導する物質として特開２００６−１１７５６６号公報にはサッカロミセス酵母から得られるマンナンがＧＬＰ−１の分泌を促進することが開示されている（特許文献１）。また特開２００６−１９９６９４号公報にはプロスタグランジン受容体のアゴニストがＧＬＰ−１の分泌促進することが開示されている（特許文献２）。その他多数のＧＬＰ分泌促進剤が報告されているが、ＧＬＰ−１分泌又は産生促進作用と化合物の相互関係は明らかになっていないため、現在のところトライアンドエラーの繰り返しで探索が行われている。
またＧＬＰ−１には空腹感を抑制する作用が有することが知られており、ダイエットに係る研究でも注目されている（非特許文献１）。したがって、生体内ＧＬＰ−１の産生を促進すれば空腹感を抑制することができ、肥満ダイエット食品に応用できれば肥満症などの患者の体重減少効果を期待できる。
As a substance that induces GLP-1 production or secretion, Japanese Patent Application Laid-Open No. 2006-117766 discloses that mannan obtained from Saccharomyces yeast promotes GLP-1 secretion (Patent Document 1). JP-A 2006-199694 discloses that an agonist of a prostaglandin receptor promotes secretion of GLP-1 (Patent Document 2). Many other GLP secretion promoters have been reported, but since the correlation between GLP-1 secretion or production promoting action and the compound has not been clarified, the search is currently being repeated by trial and error. .
GLP-1 is known to have an effect of suppressing hunger, and is also attracting attention in research related to dieting (Non-Patent Document 1). Therefore, if the production of in vivo GLP-1 is promoted, the feeling of hunger can be suppressed, and if it can be applied to an obesity diet food, an effect of reducing the weight of a patient such as obesity can be expected.
本発明者は、植物由来ステロイド配糖体画分の研究を行い、その新しい用途と作用について研究を進めたところ、玄米糠由来のアシル化ステロイド（ステロール）配糖体（以下、「ＡＳＧと略称する場合がある」）を含有する抽出画分にＧＬＰ−１産生促進作用を見出し、本発明を完成させた。
本発明は、玄米糠由来ステロール配糖体を有効成分とするＧＬＰ−１産生促進剤及びこのＧＬＰ−１産生促進組成物の利用法を提供することを課題とする。
The present inventor conducted research on plant-derived steroid glycoside fractions and researched on their new uses and actions. As a result, acylated steroid (sterol) glycoside derived from brown rice bran (hereinafter abbreviated as “ASG”). In some cases, the GLP-1 production-promoting action was found in the extracted fraction containing “)” to complete the present invention.
This invention makes it a subject to provide the utilization method of the GLP-1 production promoter which uses brown rice bran origin sterol glycoside as an active ingredient, and this GLP-1 production promotion composition.
すなわち、本発明の主な構成は、次のとおりである。
（１）玄米糠由来のアシル化ステロール配糖体を３〜15重量％含有する画分を有効成分とするＧＬＰ−１産生促進用の組成物。
（２）経口剤である（１）のＧＬＰ−１産生促進用の組成物。
（３）（１）〜（２）のいずれかに記載のＧＬＰ−１産生促進用の組成物を含有する空腹感軽減用組成物。
（４）（１）〜（２）のいずれかに記載のＧＬＰ−１産生促進用の組成物を含有するダイエット用食品。
That is, the main configuration of the present invention is as follows.
(1) A composition for promoting GLP-1 production comprising as an active ingredient a fraction containing 3 to 15% by weight of an acylated sterol glycoside derived from brown rice bran.
(2) The composition for promoting GLP-1 production according to (1), which is an oral preparation.
(3) A composition for reducing hunger sensation, comprising the composition for promoting GLP-1 production according to any one of (1) to (2).
(4) A food for diet containing the composition for promoting GLP-1 production according to any one of (1) to (2).
本発明により、玄米糠由来のアシル化ステロール配糖体が新たなＧＬＰ−１産生促進剤として提供される。特に化学式（１）で示される化合物がＧＬＰ−１産生促進組成物として有効である。本発明のＧＬＰ−１産生促進組成物は、濃度依存的にＧＬＰ−１産生促進作用を示す。本発明のＧＬＰ−１産生促進組成物は、経口摂取により小腸または大腸に存在するＧＬＰ−１産生細胞を刺激し、持続的にＧＬＰ−１産生を促進させるため、血中内のＧＬＰ−１濃度が上昇し、膵臓のβ細胞のＧＬＰ−１受容体と結合する。その結果インスリン分泌により血糖が低下するため、糖尿病用剤として利用することができる。
また空腹感を抑制する組成物を得ることができる。この組成物は、食事と同時又は食後に摂取することで、食事後の空腹を感じる時間を遅延させる効果を示す。
According to the present invention, an acylated sterol glycoside derived from brown rice bran is provided as a new GLP-1 production promoter. In particular, the compound represented by the chemical formula (1) is effective as a composition for promoting GLP-1 production. The GLP-1 production promoting composition of the present invention exhibits a GLP-1 production promoting action in a concentration-dependent manner. The composition for promoting GLP-1 production of the present invention stimulates GLP-1 producing cells existing in the small or large intestine by oral ingestion and continuously promotes GLP-1 production. Rises and binds to the GLP-1 receptor of pancreatic β cells. As a result, blood sugar decreases due to insulin secretion, and can be used as an agent for diabetes.
Moreover, the composition which suppresses a feeling of hunger can be obtained. This composition has the effect of delaying the time to feel hungry after a meal when taken at the same time as or after the meal.
本発明に用いる玄米糠抽出物に含まれるアシル化ステロール配糖体は、通常混合物である。アシル化ステロール配糖体の構成糖は主にグルコースである。構成ステロールはβ−シトステロール、スチグマステロール、カンペステロール等である。アシル基は主にグルコースの６位が、脂肪酸によってアシル化されており、構成脂肪酸は主にリノール酸、オレイン酸、パルミチン酸である（帯大研報，10，（1977）507〜514）。 The acylated sterol glycoside contained in the brown rice bran extract used in the present invention is usually a mixture. The constituent sugar of the acylated sterol glycoside is mainly glucose. The constituent sterols are β-sitosterol, stigmasterol, campesterol and the like. The acyl group is mainly acylated at the 6-position of glucose with a fatty acid, and the constituent fatty acids are mainly linoleic acid, oleic acid, and palmitic acid (Obihiro Lab., 10, (1977) 507-514).
本発明に用いられるアシル化ステロール配糖体を３〜１５質量％含有する玄米糠抽出物は、アシル化ステロール配糖体を３〜１５質量％含有すればよく、抽出方法は任意である。 The brown rice bran extract containing 3 to 15% by mass of acylated sterol glycoside used in the present invention may contain 3 to 15% by mass of acylated sterol glycoside, and the extraction method is arbitrary.
本発明に用いられる玄米糠抽出物中のアシル化ステロール配糖体の含有量の測定は以下の方法により行うことができる。
(１) 玄米糠抽出物を適量秤取し、クロロホルム／メタノール混液（クロロホルム：メタノール＝2：1）を加え、メスフラスコにてメスアップする。
(２) (２)で得られた溶液は成分濃度に応じて適宜希釈し、分析用試料溶液とする。
(３)標品はEsterified Steryl Glucoside(フナコシ社製)とし、高速液体クロマトグラフ(HPLC)法によりアシル化ステロール配糖体の濃度を算出する。
(４)高速液体クロマトグラフ法による分析条件
分析装置：HPLC
移動相A：メタノール：水 = 95：5（v/v）
移動相B：クロロホルム = 100（v/v）
ポンプ：Model 582 solvent delivery system
分析カラム：LiChrospher Si60（5μm）HPLC-Cartridge（MERCK社製）
検出器：荷電化粒子検出器（コロナダイオネクス社製）
Injection Volume：20μL
カラムオーブン：40℃（FLO社製 model 502）
分析時間：40min
脱泡装置：uniflows Degasys Ultimate DV3003
流速 ：1mL/min
グラジェント条件
以下に示すとおり
0-15分
移動相A：1％ → 25％、移動相B： 99％ → 75％
15-20分
移動相A：25％ → 90％、移動相B： 75％ → 10％
20-25分
移動相A：90％、移動相B： 10％
25-30分
移動相A：90％ → 1％、移動相B： 10％ → 99％
30-40分
移動相A：1％、移動相B： 99％
The content of the acylated sterol glycoside in the brown rice bran extract used in the present invention can be measured by the following method.
(1) Weigh a suitable amount of brown rice bran extract, add chloroform / methanol mixture (chloroform: methanol = 2: 1), and measure up in a measuring flask.
(2) The solution obtained in (2) is appropriately diluted according to the component concentration to obtain a sample solution for analysis.
(3) Esterified Steryl Glucoside (manufactured by Funakoshi) is used as a sample, and the concentration of acylated sterol glycoside is calculated by a high performance liquid chromatograph (HPLC) method.
(4) Analytical conditions by high performance liquid chromatographic method
Mobile phase A: methanol: water = 95: 5 (v / v)
Mobile phase B: chloroform = 100 (v / v)
Pump: Model 582 solvent delivery system
Analytical column: LiChrospher Si60 (5μm) HPLC-Cartridge (made by MERCK)
Detector: Charged particle detector (Corona Dionex)
Injection Volume: 20μL
Column oven: 40 ° C (model 502 manufactured by FLO)
Analysis time: 40min
Defoamer: uniflows Degasys Ultimate DV3003
Flow rate: 1mL / min
Gradient conditions As shown below
0-15 min Mobile phase A: 1% → 25%, Mobile phase B: 99% → 75%
15-20 minutes Mobile phase A: 25% → 90%, Mobile phase B: 75% → 10%
20-25 minutes Mobile phase A: 90%, Mobile phase B: 10%
25-30 minutes Mobile phase A: 90% → 1%, Mobile phase B: 10% → 99%
30-40 minutes Mobile phase A: 1%, Mobile phase B: 99%
[ＡＳＧ構成成分の分析]
上記のＨＰＬＣ法で分離したＡＳＧをＬＣマススペクトル法で分析し、構成する糖質、脂肪酸、ステロールを分析した。
ＬＣ／ＭＳの条件は以下のとおりである。
検出器：ＬＣＭＳ−２０２０（島津製作所社製）、ＡＰＣＩ：ポジティブモード、カラム：ＵＧ１２０（５μｍ、４．６ｍｍ Ｉ．Ｄ×２５０ｍｍ （資生堂社製）、カラム温度：５５℃、流速 １ｍＬ/ｍin、注入量 ２０μＬ、移動相 アセトン：メタノール＝５０：５０（ｖ/ｖ）、分析時間 １３０分。
分析結果を下記の表1に示す。
[ASG component analysis]
The ASG separated by the above HPLC method was analyzed by the LC mass spectrum method, and the constituent carbohydrates, fatty acids and sterols were analyzed.
The conditions for LC / MS are as follows.
Detector: LCMS-2020 (manufactured by Shimadzu Corporation), APCI: positive mode, column: UG120 (5 μm, 4.6 mm ID × 250 mm (manufactured by Shiseido), column temperature: 55 ° C., flow rate 1 mL / min, injection Amount 20 μL, mobile phase acetone: methanol = 50: 50 (v / v), analysis time 130 minutes.
The analysis results are shown in Table 1 below.
本発明に用いられる玄米糠抽出物の抽出方法としては、溶媒抽出法、超臨界抽出法等が挙げられる。
具体的な抽出操作を以下に示す。また、得られた玄米糠抽出物をカラムクロマトグラフィーで生成し、アシル化ステロール配糖体を濃縮してもよい。
（抽出方法 溶媒抽出方法）
市場に流通している玄米糠を選別した後にノルマルヘキサンなどの溶媒を用いて脱脂する。得られた油、脱脂糠などの粗原料を蒸留装置により脱溶媒し、さらにノルマルヘキサン、アセトン、エタノールなどの溶媒によって抽出する。得られた抽出液を、脱溶剤装置を用いて再度脱溶剤することで玄米糠抽出物を得ることができる。玄米糠抽出物はその他の成分として、トリグリセライド油、レシチンを含む。
Examples of the method for extracting the brown rice bran extract used in the present invention include a solvent extraction method and a supercritical extraction method.
A specific extraction operation is shown below. Moreover, the obtained brown rice bran extract may be produced by column chromatography to concentrate the acylated sterol glycoside.
(Extraction method Solvent extraction method)
After selecting brown rice bran that is distributed in the market, it is degreased using a solvent such as normal hexane. The obtained crude raw materials such as oil and defatted lees are desolvated with a distillation apparatus, and further extracted with a solvent such as normal hexane, acetone and ethanol. A brown rice bran extract can be obtained by removing the solvent again from the obtained extract using a solvent removal apparatus. The brown rice bran extract contains triglyceride oil and lecithin as other components.
本発明のＧＬＰ−１産生促進組成物は、糖尿病治療剤、空腹感軽減用組成物、ダイエット用食品として、あるいは動物用医薬として利用することができる。剤型は、公知の方法により助剤とともに任意の形態に製剤化して、経口摂取（投与）することができる。カプセル剤又は錠剤、顆粒剤、細粒剤、散剤、液状として摂取（投与）できる。
摂取（投与）量は、摂取（投与）方法と、対象者の年齢、病状や一般状態等によって変化し得るが、成人では体重1kg当たり通常、１日当たり有効成分として0.１〜500mgが適当である。
The composition for promoting production of GLP-1 of the present invention can be used as a therapeutic agent for diabetes, a composition for reducing hunger, a food for diet, or a pharmaceutical for animals. The dosage form can be formulated into an arbitrary form together with an auxiliary agent by a known method and taken orally (administered). It can be ingested (administered) as a capsule or tablet, granule, fine granule, powder, or liquid.
The intake (administration) amount may vary depending on the intake (administration) method and the subject's age, medical condition, general condition, etc. In adults, 0.1 to 500 mg as an active ingredient per day is usually appropriate for 1 kg of body weight. is there.
＜玄米糠由来のアシル化ステロール配糖体の調製について＞
１．糠成分を採取する玄米は、玄米又は発芽玄米を原料として用いることができる。発芽玄米は公知の方法により調製することができる。本出願人は、発芽玄米について多数の提案をしており、例えば、特許第３４２３９２７号公報、特許第３６１１８０４号公報、特許第３７３８０２５号公報等に開示された発芽玄米の製法によって得ることができる。
玄米又は発芽玄米を5〜15％程度搗精して糠成分を採取する。この糠成分を最初にヘキサンにて脱脂する。この脱脂工程は、一般の糠を脱脂して米糠油を採取する方法と同様である。したがって、脱脂処理後の廃棄される米糠を使用することもできる。
本発明では、例えば、この脱脂糠を原料として、さらに、有機溶媒を用いてアシル化ステロール配糖体画分を抽出する。
その他の方法としては、玄米糠を物理的に圧縮して得られた油からアシル化ステロール配糖体を抽出する事も出来る。
<About the preparation of acylated sterol glycosides derived from brown rice bran>
1. The brown rice from which the koji component is collected can be brown rice or germinated brown rice as a raw material. Germinated brown rice can be prepared by a known method. The present applicant has made a number of proposals for germinated brown rice, which can be obtained, for example, by the method for producing germinated brown rice disclosed in Japanese Patent No. 3423927, Japanese Patent No. 3611804, Japanese Patent No. 3738025, and the like.
Refine brown rice or germinated brown rice about 5 to 15% and collect the koji ingredients. The soot component is first degreased with hexane. This degreasing step is the same as the method for collecting rice bran oil by degreasing general rice bran. Therefore, the rice bran discarded after the degreasing treatment can also be used.
In the present invention, for example, an acylated sterol glycoside fraction is further extracted using this defatted koji as a raw material and using an organic solvent.
As another method, acylated sterol glycoside can be extracted from oil obtained by physically compressing brown rice bran.
２．本発明に係る発芽玄米糠由来のアシル化ステロール配糖体とは式（１）に示す構造のステロール配糖体を含有する。このアシル化ステロール配糖体を以下ＡＳＧと略称する。 2. The acylated sterol glycoside derived from germinated brown rice bran according to the present invention contains a sterol glycoside having a structure represented by the formula (1). This acylated sterol glycoside is hereinafter abbreviated as ASG.
パルミトイル基
オレオイル基
リノレオイル基
(ii) 化学式（１）中のＹは以下の群から選択されるいずれかである。
β-シトステリル基
カンペステリル基
スチグマステリル基
有機溶媒による玄米糠抽出物中にはアシル化ステロール配糖体を３％以上含有する組成物が本発明の実施上好ましい。また高度に精製したアシル化ステロール配糖体を食品中に直接配合してもよい。アシル化ステロール配糖体を食品に配合する場合は３％以上の濃度
にすることが好ましい。
Palmitoyl group Oleoyl group Linoleic oil group
(ii) Y in the chemical formula (1) is any one selected from the following group.
β-Sitosteryl group Campesteryl group Stigmasteryl group
A composition containing 3% or more of an acylated sterol glycoside in the brown rice bran extract using an organic solvent is preferred in the practice of the present invention. Highly purified acylated sterol glycosides may also be directly incorporated into foods. When the acylated sterol glycoside is added to food, the concentration is preferably 3% or more.
以下に実施例を示し、本発明をさらに詳細に説明する。 The following examples illustrate the present invention in more detail.
＜実施例１＞
市場に流通している玄米糠を選別し胚乳や異物を除いた玄米糠を得た。得られた選別済みの玄米糠1kgに対して50Lの割合でノルマルヘキサンを用い脱脂した。この脱脂作業を3回繰り返し、脱脂糠を得た。得られた脱脂糠を蒸留装置により溶媒を除去した。得られた
脱脂糠8kgに対し、50Lの割合のエタノールによって70℃にて1時間、3回抽出し、得られた抽出液について、脱溶剤装置を用いて脱溶剤を行った。脱溶剤した抽出物をろ過することで得られた玄米糠抽出物のアシル化ステロール配糖体の含有量は３．4質量％であった。
<Example 1>
The unpolished rice bran circulated in the market was selected to obtain the unpolished rice bran from which endosperm and foreign matter were removed. The obtained unpolished rice bran 1 kg was defatted using normal hexane at a rate of 50 L. This degreasing operation was repeated three times to obtain a degreased soot. The solvent was removed from the obtained defatted lees using a distillation apparatus. 8 kg of the obtained defatted soot was extracted with 50 L of ethanol at 70 ° C. for 1 hour and 3 times, and the obtained extract was subjected to solvent removal using a solvent removal apparatus. The content of acylated sterol glycoside in the brown rice bran extract obtained by filtering the solvent-free extract was 3.4% by mass.
＜実施例２＞
参考例1で得られた玄米糠抽出物20gに対し20mlのヘキサンとクロロホルムを1：1の割合で混合した溶媒を加えた。シリカゲルにヘキサン：クロロホルムを1：1の割合で混合した溶媒を加えて膨潤させ、直径5cm、長さ60cmのカラム内に充填し、その後に、同組成の溶媒を十分に浸透させた。玄米糠抽出物とヘキサンとクロロホルムの混合溶液をカラム上に注ぎ、完全にシリカゲル内に浸透させた。その後、ヘキサンとクロロホルムを1:1の割合で混合した溶媒1000mlを加え、カラム下部から排出した。ヘキサンとクロロホルムの溶媒がすべて排出された後に、さらにクロロホルムを2000ml加え、カラム下部から排出した。
クロロホルムがすべて排出された後にクロロホルム：メタノールを9:1の割合で混合した溶媒1000mlを加え、溶出液を回収した。得られた溶出液について、エバポレーターを用いて脱溶媒した。得られた玄米糠抽出物中のアシル化ステロール配糖体の含有量は12．0質量％であった。
<Example 2>
To 20 g of the brown rice bran extract obtained in Reference Example 1, 20 ml of hexane and chloroform mixed at a ratio of 1: 1 was added. A solvent in which hexane: chloroform was mixed at a ratio of 1: 1 to silica gel was added to swell, filled in a column having a diameter of 5 cm and a length of 60 cm, and then sufficiently infiltrated with the solvent having the same composition. The brown rice bran extract and a mixed solution of hexane and chloroform were poured onto the column and completely infiltrated into the silica gel. Thereafter, 1000 ml of a solvent in which hexane and chloroform were mixed at a ratio of 1: 1 was added and discharged from the bottom of the column. After all the hexane and chloroform solvents were discharged, 2000 ml of chloroform was further added and discharged from the bottom of the column.
After all the chloroform was discharged, 1000 ml of a solvent mixed with chloroform: methanol in a ratio of 9: 1 was added, and the eluate was collected. The obtained eluate was desolvated using an evaporator. The content of acylated sterol glycoside in the obtained brown rice bran extract was 12.0% by mass.
試験例
［細胞培養試験］
NCI-H716細胞(ヒト結腸がん由来細胞)を1×105cellsを75cm2 の細胞培養フラスコに播種し、10% FBS含有RPMI1640培地で14日間、３７℃、5％ＣＯ２条件下で、培養を行った。なお NCI-H716細胞は、ATCC（American Type Culture Collection）から入手した。
培養後、マトリゲルを塗布した24 well plateに4×104cells/wellとなるように播種し、10%FBS含有DMEM培地で1日間培養を行った。
その後、Hanks緩衝液で2回洗浄し、試験試料を添加し、無血清DMEM培地で2時間培養を行った。培養終了後、培養液中に産生されたＧＬＰ−１量を「GLP-1 ELISA kit (Glucagon-Like Peptide-1 Cat＃EGLP-35K：Millipore社)」を用いて測定した。なお、コントロールは1％DMSOとし、陽性対照として用いたオレオイルエタノールアミド(OEA)は、ＧＬＰ−１産生促進査証を有することが知られている化合物である。このＯＥＡを100μMとなるように添加した。
Test example [Cell culture test]
NCI-H716 cells (human colon cancer-derived cells) are seeded in 1 x 105 cells in a 75 cm2 cell culture flask and cultured in 10% FBS-containing RPMI1640 medium for 14 days at 37 ° C and 5% CO 2. It was. NCI-H716 cells were obtained from ATCC (American Type Culture Collection).
After culturing, the cells were seeded at a density of 4 × 10 4 cells / well in a 24-well plate coated with Matrigel, and cultured in DMEM medium containing 10% FBS for 1 day.
Thereafter, the cells were washed twice with Hanks buffer, a test sample was added, and the cells were cultured for 2 hours in serum-free DMEM medium. After completion of the culture, the amount of GLP-1 produced in the culture solution was measured using “GLP-1 ELISA kit (Glucagon-Like Peptide-1 Cat # EGLP-35K: Millipore)”. The control is 1% DMSO, and oleoylethanolamide (OEA) used as a positive control is a compound known to have a GLP-1 production promotion visa. This OEA was added to a concentration of 100 μM.
[試験物質]
実施例1及び2で得られたアシル化ステロール配糖体（ＡＳＧ）を含有する玄米からの抽出物を試験に用いた。ＡＳＧを含有する玄米糠抽出物の濃度が1000μg/ml/1％DMSO(ジメチルスルフォキシド)となるように、DMEM(FBS-,PS-)培地で溶解し、最終培養液中のＡＳＧを3.4％含有する玄米糠抽出物の濃度は、２５０μｇ／ｍｌ、５００μｇ／ｍｌ、１０００μｇ／ｍｌになるように、12.0％含有する玄米糠抽出物の濃度は333μｇ/ｍｌになるよう添加した。
[Test substance]
The extract from brown rice containing the acylated sterol glycoside (ASG) obtained in Examples 1 and 2 was used for the test. Dissolve the brown rice bran extract containing ASG in a DMEM (FBS-, PS-) medium so that the concentration of the brown rice bran extract is 1000 μg / ml / 1% DMSO (dimethyl sulfoxide). The concentration of the brown rice bran extract containing 12.0% was added so that the concentration of the brown rice bran extract containing 12.0% was 333 μg / ml so that the concentration of the brown rice bran extract containing 1% was 250 μg / ml, 500 μg / ml, and 1000 μg / ml.
[結果]
ＧＬＰ−１測定結果はＤＭＳＯのみの場合に得られる測定値を１としたとき、オレオイルエタノールアミド(OEA)、ＡＳＧを含む組成物２５０μｇ／ｍｌ、５００μｇ／ｍｌ、１０００μｇ／ｍｌのそれぞれの相対値として求めた。測定結果を図１に示す。ＡＳＧにＯＥＡと同等以上のＧＬＰ−１産生促進作用が確認され、さらに濃度依存性も認められた。
なお玄米糠由来の脂質画分であってＡＳＧを含有しないものにはＧＬＰ−１産生促進効果が認められなかった。
[result]
The GLP-1 measurement results are relative values of 250 μg / ml, 500 μg / ml, and 1000 μg / ml of the composition containing oleoylethanolamide (OEA) and ASG, when the measured value obtained with DMSO alone is 1. As sought. The measurement results are shown in FIG. ASG was confirmed to have a GLP-1 production promoting effect equivalent to or higher than that of OEA, and concentration dependency was also observed.
In addition, the GLP-1 production promotion effect was not recognized by the lipid fraction derived from brown rice bran but not containing ASG.
試験例
［満腹感の持続性の確認試験］
実施例１で得た玄米糠抽出物が満腹感を持続させる作用を有することを確認した。
（１）方法
・対象
健常な成人男性15名
・試験食品
被験品は、玄米糠抽出物185.6mgを含むソフトカプセル錠剤とした。プラセボカプセルは、玄米糠抽出物を含まないソフトカプセル錠剤とした。
・試験デザイン
試験デザインは、プラセボ群を対象とするランダム化したクロスオーバー二重盲検比較試験とした。摂取量は玄米糠抽出物カプセル、プラセボカプセルともに指定食摂取後に9粒を水250mlとともに摂取した。玄米糠抽出物摂取日とプラセボ摂取日は、ウォッシュアウトを1週間以上あけて実施した。
・検査方法
主観的自覚観察（ＶＡＳ）による満腹感調査を行った。
Test example [Confirmation test of satiety]
It was confirmed that the brown rice bran extract obtained in Example 1 has an action of maintaining a feeling of fullness.
(1) Methods / Subjects 15 healthy adult males and test food The test article was a soft capsule tablet containing 185.6 mg of brown rice bran extract. The placebo capsules were soft capsule tablets containing no brown rice bran extract.
• Study design The study design was a randomized crossover double-blind comparative study in the placebo group. Ingestion of 9 grains of brown rice bran extract capsules and placebo capsules together with 250 ml of water after ingestion of the specified meal. On the day of brown rice bran extract ingestion and placebo ingestion, washout was performed for at least one week.
-Examination method A satiety survey was conducted by subjective subjective observation (VAS).
（２）試験結果
・主観的自覚観察（満腹度測定)
測定結果を図２に示す。指定食摂取60分後と90分後において、プラセボ群に比較し玄米糠抽出物摂取群で有意な差がみられた。
・本試験の評価
本試験では、健常者が玄米糠抽出物を摂取することによって、満腹感が維持するか検討した。その結果、本試験では、プラセボ群に比較して玄米糠抽出物群の満腹感調査で有意な差が見られた。
したがって本発明の組成物は満腹感の持続作用を有することが確認された。
(2) Test results / subjective subjective observation (measuring satiety)
The measurement results are shown in FIG. Significant differences were observed in the brown rice bran extract ingestion group compared to the placebo group at 60 and 90 minutes after ingestion of the designated diet.
-Evaluation of this test In this test, it was examined whether a healthy person maintained a feeling of fullness by ingesting brown rice bran extract. As a result, in this study, a significant difference was found in the satiety survey of the brown rice bran extract group compared to the placebo group.
Therefore, it was confirmed that the composition of the present invention has a continuous feeling of fullness.
以下に本発明のＡＳＧを用いた経口剤の処方例を示す。
処方例１
[カプセル剤]
組成
ＡＳＧ１０％含有組成物 １００ｍｇ
ミツロウ １０ｍｇ
ぶどう種子オイル １１０ｍｇ
上記成分を混合し、ゼラチンおよびグリセリンからなるカプセル基剤中に充填し、軟カプセルを得た。
Examples of oral formulations using the ASG of the present invention are shown below.
Formulation Example 1
[Capsule]
Composition Composition containing 10% ASG 100mg
Beeswax 10mg
Grape seed oil 110mg
The above ingredients were mixed and filled into a capsule base composed of gelatin and glycerin to obtain soft capsules.
処方例２
[錠剤]
組成
ＡＳＧ１０％含有組成物 １５０ｍｇ
セルロース ８０ｍｇ
デンプン ２０ｍｇ
ショ糖脂肪酸エステル ２ｍｇ
上記成分を混合、打錠し、錠剤を得た。
Formulation Example 2
[tablet]
Composition 150 mg ASG 10% composition
Cellulose 80mg
Starch 20mg
Sucrose fatty acid ester 2mg
The above components were mixed and tableted to obtain tablets.
処方例３
[液剤]
組成 （配合；質量％）
果糖ブドウ糖液糖 ５．００
クエン酸 １０．４
Ｌ−アスコルビン酸 ０．２０
香料 ０．０２
色素 ０．１０
ＡＳＧ１０％含有組成物 １．００
水 ８２．２８
Formulation Example 3
[Liquid]
Composition (formulation; mass%)
Fructose glucose liquid sugar 5.00
Citric acid 10.4
L-ascorbic acid 0.20
Perfume 0.02
Dye 0.10
Composition containing 10% ASG 1.00
Water 82.28
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