JP2006342084A - Gip secretion inhibitor - Google Patents
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Abstract
Description
本発明は、医薬または食品として有用なGIP分泌抑制剤に関する。 The present invention relates to a GIP secretion inhibitor useful as a medicine or food.
Gastric inhibitory polypeptide(GIP)は、胃酸分泌抑制作用や胃運動抑制作用を有する消化管ホルモンであり、摂食時、食餌中の脂質等によりその分泌が亢進されることが知られている(非特許文献1〜3)。そのため、GIPの分泌を阻害する物質は、消化促進や胃もたれの改善に有用であると考えられる。そして、これまでの研究によって、GIPの機能を阻害する物質として、3−ブロモ−5−メチル−2−フェニルピラゾロ[1,5−a]ピリミジン−7−オール(BMPP)が知られ、食後GIPの分泌を抑制するものとして、グアガム等が知られている(特許文献1、非特許文献4〜9)。しかしながら、前者の物質は、in vivoにおけるGIP機能阻害効果が確認されておらず、また後者の物質は脂質摂取時のGIP分泌抑制効果が検討されていないという問題があり、また、胃もたれ改善効果等の点で必ずしも十分なものとはいえない。 Gastric inhibitory polypeptide (GIP) is a gastrointestinal hormone having gastric acid secretion inhibitory action and gastric motility inhibitory action, and it is known that its secretion is enhanced by lipids in the diet during feeding (non-patent) Literatures 1-3). Therefore, it is considered that a substance that inhibits GIP secretion is useful for promoting digestion and improving stomach sag. As a result of research so far, 3-bromo-5-methyl-2-phenylpyrazolo [1,5-a] pyrimidin-7-ol (BMPP) is known as a substance that inhibits the function of GIP. Gua gum etc. are known as what suppresses secretion of GIP (patent document 1, nonpatent literatures 4-9). However, the former substance has not been confirmed to have an inhibitory effect on GIP function in vivo, and the latter substance has a problem that the effect of suppressing GIP secretion upon lipid intake has not been studied. However, it is not necessarily sufficient in terms of the above.
一方、ジアシルグリセロールは、食後の血中中性脂肪の上昇抑制作用(特許文献2)や、血中HDLコレステロール上昇作用を有し(特許文献3)、調理油や種々の油脂加工食品に使用されている。また、ジアシルグリセロールは、抗肥満効果(非特許文献10、11)や脂肪肝改善(非特許文献12)などの効果を奏することが知られている。
しかしながら、ジアシルグリセロールとGIP分泌との関係については知られていなかった。
However, the relationship between diacylglycerol and GIP secretion has not been known.
本発明の目的は、医薬または食品として有用なGIP分泌抑制剤を提供することにある。 An object of the present invention is to provide a GIP secretion inhibitor useful as a medicine or food.
本発明者らは、ジアシルグリセロールが、食後のGIP分泌を著しく抑制し、消化促進や胃もたれ改善に有用であることを見出した。 The present inventors have found that diacylglycerol remarkably suppresses postprandial GIP secretion and is useful for promoting digestion and improving stomach sag.
すなわち本発明は、ジアシルグリセロールを有効成分とする食後GIP分泌抑制剤を提供するものである。 That is, the present invention provides a postprandial GIP secretion inhibitor containing diacylglycerol as an active ingredient.
また本発明は、ジアシルグリセロールを有効成分とし、消化促進または胃もたれの改善のために用いられるものである旨の表示を付した食品を提供するものである。 In addition, the present invention provides a food with a label indicating that diacylglycerol is an active ingredient and is used for promoting digestion or improving stomach sag.
本発明のGIP分泌抑制剤を用いれば、食後のGIPを減少させることができ、消化吸収を促進することができ、胃もたれの改善を図ることができる。 If the GIP secretion inhibitor of this invention is used, GIP after a meal can be reduced, digestion absorption can be accelerated | stimulated and the improvement of stomach sag can be aimed at.
ジアシルグリセロールとしては、グリセリンの1位と2位の水酸基が脂肪酸でエステル化されたもの(1,2−ジアシルグリセロール)及び1位と3位の水酸基が脂肪酸でエステル化されたもの(1,3−ジアシルグリセロール)が挙げられるが、1,2−ジアシルグリセロールが好ましい。本発明においては、これらそれぞれを単独で又は双方の混合物として用いることができる。脂肪酸残基の炭素数に特に制限はないが、8〜24、特に16〜22が好ましい。脂肪酸残基としては、飽和のもの及び不飽和のものが挙げられ、かかる残基としては、カプリル酸、カプリン酸、ラウリル酸、ミリスチン酸、パルミチン酸、ステアリン酸、オレイン酸、リノール酸、リノレイン酸、エイコサペンタエン酸、ドコサヘキサエン酸由来のアシル基、或いはこれらの混合物や、これらの酸を含有する牛脂、豚脂等の動物油、パーム油、菜種油、大豆油、サフラワー油、トウモロコシ油、シソ油、トウハゼ油、アマニ油、エノ油等の植物油から誘導される脂肪酸等由来のアシル基が挙げられる。これらのジアシルグリセロールは一種又は二種以上を用いることができる。なお、かかるジアシルグリセロールを混合物として用いる場合、不飽和脂肪酸残基の量は、全脂肪酸残基の55%以上であることが好ましく、更には70%以上、特に90%以上が好ましい。更に不飽和脂肪酸がオレイン酸15〜85%、リノール酸15〜85%で構成されることが最も好ましい。なお、構成脂肪酸含量は、構成アシル基を脂肪酸に換算して算出する。 Diacylglycerols include those in which the hydroxyl groups at the 1st and 2nd positions of glycerin are esterified with fatty acids (1,2-diacylglycerol) and those in which the 1st and 3rd hydroxyl groups are esterified with fatty acids (1,3 -Diacylglycerol), but 1,2-diacylglycerol is preferred. In the present invention, each of these can be used alone or as a mixture of both. Although there is no restriction | limiting in particular in carbon number of a fatty acid residue, 8-24, especially 16-22 are preferable. Fatty acid residues include saturated and unsaturated, such residues include caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid , Acyl groups derived from eicosapentaenoic acid, docosahexaenoic acid, or a mixture thereof, animal oils such as beef tallow and lard containing these acids, palm oil, rapeseed oil, soybean oil, safflower oil, corn oil, perilla oil, Examples include acyl groups derived from fatty acids derived from vegetable oils such as tomato oil, linseed oil and eno oil. These diacylglycerols can be used alone or in combination of two or more. When such a diacylglycerol is used as a mixture, the amount of unsaturated fatty acid residues is preferably 55% or more of the total fatty acid residues, more preferably 70% or more, and particularly preferably 90% or more. The unsaturated fatty acid is most preferably composed of 15 to 85% oleic acid and 15 to 85% linoleic acid. The constituent fatty acid content is calculated by converting the constituent acyl group into a fatty acid.
本発明で使用するジアシルグリセロールは、特開平4−300825号公報等に記載の方法、例えば、牛脂、豚脂等の動物油、パーム油、菜種油、大豆油、サフラワー油、トウモロコシ油、シソ油、トウハゼ油、アマニ油、エノ油、米糠油、コーン油、パーム油、オリーブ油、シゴマ油、エグマ油、亜麻仁油等の植物油、魚油等のトリグリセリド油とグリセリンとのエステル交換反応、または油脂由来の脂肪酸とグリセリンとのエステル化反応等任意の方法により得ることができる。反応方法は、アルカリ触媒等を用いた化学反応法、リパーゼ等の油脂加水分解酵素を用いた生化学反応法等が挙げられるが、外観上の観点から、生化学反応法が好ましい。尚、ジアシルグリセロールの製造においては、副生成物としてモノ体及びトリ体が含まれるが、これらの副生成物は、本発明の効果を損なわない範囲においてジ体と共に用いられてもよい。 The diacylglycerol used in the present invention is a method described in JP-A-4-3000082, for example, animal oil such as beef tallow and lard, palm oil, rapeseed oil, soybean oil, safflower oil, corn oil, perilla oil, Sucrose oil, flaxseed oil, eno oil, rice bran oil, corn oil, palm oil, olive oil, sigma oil, egg oil, linseed oil, etc. It can obtain by arbitrary methods, such as esterification reaction of glycerin. Examples of the reaction method include a chemical reaction method using an alkali catalyst and the like, a biochemical reaction method using an oil and fat hydrolase such as lipase, and the like. From the viewpoint of appearance, a biochemical reaction method is preferable. In the production of diacylglycerol, mono- and tri-isomers are included as by-products, but these by-products may be used together with the di-isomer within a range not impairing the effects of the present invention.
そして、ジアシルグリセロールは、後記実施例に示すように、一般的な油であるトリアシルグリセロールに比べて優れたGIP分泌抑制効果を有することから、例えば、トリアシルアシルグリセロールの代わりに食材として用いることにより、食後のGIPを減少させ、消化吸収を促進させるなどの効果を発揮し得る。従って、本発明のジアシルグリセロールは、食後GIP分泌抑制剤として、ヒト若しくは動物用の食品又は医薬品の素材となり得る。 As shown in the examples below, diacylglycerol has an excellent GIP secretion inhibitory effect compared to triacylglycerol, which is a common oil, so it can be used as a foodstuff instead of triacylglycerol, for example. Thus, it is possible to exert effects such as reducing GIP after meals and promoting digestion and absorption. Therefore, the diacylglycerol of the present invention can be used as a food or pharmaceutical material for humans or animals as a postprandial GIP secretion inhibitor.
本発明の食後GIP分泌抑制剤は、本発明のジアシルグリセロールを単体でヒト及び動物に投与できる他、各種飲食品、医薬品、ペットフード等に配合して摂取することができる。食品としては、胃酸分泌抑制、消化促進、胃もたれ改善等の改善のために用いられるものである旨の表示を付した美容食品、病者用食品、特定保健用食品等の食品に応用できる。医薬品として使用する場合は、例えば、錠剤、顆粒剤等の経口用固形製剤や、内服液剤、シロップ剤等の経口用液体製剤とすることができる。 The postprandial GIP secretion inhibitor of the present invention can be administered in combination with various foods, medicines, pet foods, etc. in addition to the diacylglycerol of the present invention alone administered to humans and animals. As the food, it can be applied to foods such as beauty foods, foods for sick people, foods for specified health use, etc., which are used for improvement of gastric acid secretion suppression, digestion promotion, stomach sag improvement and the like. When used as a pharmaceutical, for example, oral solid preparations such as tablets and granules, and oral liquid preparations such as oral liquids and syrups can be used.
尚、経口用固形製剤を調製する場合には、本発明のジアシルグリセロールに賦形剤、必要に応じて結合剤、崩壊剤、滑沢剤、着色剤、矯味剤、矯臭剤等を加えた後、常法により錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等を製造することができる。また、経口用液体製剤を調製する場合は、矯味剤、緩衝剤、安定化剤、矯味剤等を加えて常法により内服液剤、シロップ剤、エリキシル剤等を製造することができる。 When preparing an oral solid preparation, after adding an excipient, if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a corrigent, a corrigent and the like to the diacylglycerol of the present invention. Tablets, coated tablets, granules, powders, capsules and the like can be produced by conventional methods. Moreover, when preparing a liquid preparation for oral use, a liquid preparation, a syrup, an elixir, etc. can be manufactured by a conventional method by adding a corrigent, a buffer, a stabilizer, a corrigent and the like.
上記各製剤中に配合されるべきジアシルグリセロールの配合量は、通常0.1重量%、好ましくは1重量%、更に好ましくは5重量%とするのが好ましい。 The blending amount of diacylglycerol to be blended in each of the above preparations is usually 0.1% by weight, preferably 1% by weight, more preferably 5% by weight.
本発明の食後GIP分泌抑制剤または食品の投与量(有効摂取量)は、ジアシルグリセロールとして、一日当り0.01g/kg体重以上とするのが好ましく、特に0.1g/kg体重以上、更に0.2g/kg体重以上とするのが好ましい。 The dose (effective intake) of the postprandial GIP secretion inhibitor or food of the present invention is preferably 0.01 g / kg body weight or more per day, particularly 0.1 g / kg body weight or more, more preferably 0 as diacylglycerol. .2g / kg body weight or more is preferable.
製造例1 ジアシルグリセロール・トリアシルグリセロールの製造
以下の実施例で用いたジアシルグリセロールは下記の方法で製造したものである。固定化1,3−位選択的リパーゼである市販リパーゼ製剤(商品名「Lipozyme IM−20」、ノボインダストリーA.S.社製)を触媒として、表1の脂肪酸組成を有するジアシルグリセロールを得た。トリアシルグリセロールは大豆油と菜種油を混合し、表1に示す脂肪酸組成に混合したものを得た。
Production Example 1 Production of Diacylglycerol / Triacylglycerol Diacylglycerol used in the following examples was produced by the following method. A diacylglycerol having the fatty acid composition shown in Table 1 was obtained using a commercially available lipase preparation (trade name “Lipozyme IM-20”, manufactured by Novo Industry AS, Inc.), which is an immobilized 1,3-position selective lipase, as a catalyst. . Triacylglycerol was obtained by mixing soybean oil and rapeseed oil and mixing them with the fatty acid composition shown in Table 1.
実施例1 ジアシルグリセロールのGIP分泌抑制作用
マウス(C57BL/6J雄、9週令)を1群11、または16匹とし、製造例1で得られたトリアシルグリセロール(TAG)、またはジアシルグリセロール(DAG)2mg/g体重を、単独、あるいは0.02mg卵黄レシチンによりグルコース2mg/g体重とエマルジョンにしたものを、ゾンデにより経口投与した。10分後、腹部大静脈より採血し、血中GIPを測定した。10分後のマウス血中のGIP量を表2に示す。
Example 1 GIP secretion inhibitory action of diacylglycerol Mice (C57BL / 6J male, 9 weeks old) were grouped as 11 or 16 mice, and triacylglycerol (TAG) or diacylglycerol (DAG) obtained in Production Example 1 was used. ) 2 mg / g body weight, alone or 0.02 mg egg yolk lecithin, which was made into an emulsion with 2 mg / g body weight of glucose, was orally administered using a sonde. Ten minutes later, blood was collected from the abdominal vena cava and blood GIP was measured. The amount of GIP in the mouse blood after 10 minutes is shown in Table 2.
表2の結果から、ジアシルグリセロールを摂取したマウスでは、対照であるトリアシルグリセロールを摂取したマウスに比較して、グルコース共存の有無にかかわらず、血中GIPが低く、血中へのGIP分泌抑制効果が認められることがわかる。 From the results shown in Table 2, in mice fed with diacylglycerol, blood GIP was low regardless of the presence or absence of glucose compared to mice fed with triacylglycerol as a control, and inhibition of GIP secretion into blood was observed. It turns out that an effect is recognized.
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JP2010222284A (en) * | 2009-03-23 | 2010-10-07 | Kao Corp | Blood gip increase inhibitor |
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JP2011080803A (en) * | 2009-10-05 | 2011-04-21 | Kao Corp | Method of evaluating or selecting gip elevation inhibitor |
JP2011080804A (en) * | 2009-10-05 | 2011-04-21 | Kao Corp | Method for evaluating or selecting gip-rise inhibitor |
JP2012515139A (en) * | 2009-01-16 | 2012-07-05 | 花王株式会社 | GIP elevation inhibitor |
JP2012171915A (en) * | 2011-02-22 | 2012-09-10 | Kao Corp | Gip increase inhibitor |
JP2018104422A (en) * | 2016-12-26 | 2018-07-05 | 花王株式会社 | Agent for improvement of hypothermia |
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EP2011492A4 (en) * | 2006-04-24 | 2009-08-19 | Kao Corp | Gip secretion inhibitor |
JP2012515139A (en) * | 2009-01-16 | 2012-07-05 | 花王株式会社 | GIP elevation inhibitor |
JP2010222284A (en) * | 2009-03-23 | 2010-10-07 | Kao Corp | Blood gip increase inhibitor |
WO2010116760A1 (en) * | 2009-04-10 | 2010-10-14 | 花王株式会社 | Inhibitor for elevation of gip level |
JP2010260856A (en) * | 2009-04-10 | 2010-11-18 | Kao Corp | Inhibitor for elevation of gip level |
JP2011080803A (en) * | 2009-10-05 | 2011-04-21 | Kao Corp | Method of evaluating or selecting gip elevation inhibitor |
JP2011080804A (en) * | 2009-10-05 | 2011-04-21 | Kao Corp | Method for evaluating or selecting gip-rise inhibitor |
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