CN101426491A - Gip分泌抑制剂 - Google Patents
Gip分泌抑制剂 Download PDFInfo
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- CN101426491A CN101426491A CNA2007800143766A CN200780014376A CN101426491A CN 101426491 A CN101426491 A CN 101426491A CN A2007800143766 A CNA2007800143766 A CN A2007800143766A CN 200780014376 A CN200780014376 A CN 200780014376A CN 101426491 A CN101426491 A CN 101426491A
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- monoacylglycerol
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- A—HUMAN NECESSITIES
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- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/158—Fatty acids; Fats; Products containing oils or fats
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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Abstract
本发明提供了作为医药或食品有用的GIP分泌抑制剂。本发明提供的饮食后GIP分泌抑制剂以单酰甘油为有效成分。
Description
技术领域
本发明涉及作为医药或食品有用的GIP分泌抑制剂。
背景技术
现代饮食生活是，从1960年当时开始的摄取的卡路里基本平稳，而摄取的脂质比例则从1.1比例增加至2.7比例，变化非常大(国民营养调查)。如此，高脂肪饮食会对胃造成负担，引起胃积食等问题。
抑胃多肽(Gastric inhibitory polypeptide，GIP)是已知具有胃酸分泌抑制作用和胃运动抑制作用的消化管激素，已知在摄取食物时，食物中的脂质等会促进其分泌(非专利文献1～3)。因此，减少GIP的分泌被认为对于促进消化和改善胃积食是有用的。并且，根据迄今为止的研究，作为阻碍GIP功能的物质已知有3-溴-5-甲基-2-苯基吡唑并[1，5-a]嘧啶-7-醇(BMPP)，作为抑制GIP分泌的物质已知有瓜尔胶等(专利文献1，非专利文献4～9)。但是，问题在于：前者的BMPP在体内阻碍GIP功能的效果没有得到确认，而后者的瓜尔胶等在摄取脂质时抑制GIP分泌的效果也没有得到研究，而且，就改善胃积食的效果等方面而言不能说一定是充分的。而且，期待有即使每日摄取安全性也是优异的物质。
另一方面，单酰甘油(以下也称作MAG)是在食品领域内作为乳化剂等应用广泛安全性优异的物质，通常以0.2～0.5％左右配合于人造黄油、乳饮料、冰淇淋、面包等中(非专利文献10、11)。另外，已知单酰甘油具有抑制饮食后血中甘油三酯上升的作用(专利文献2)。
但是，单酰甘油与GIP分泌的关系还是未知的。
【专利文献1】国际公开第01/87341号小册子
【专利文献2】日本特开平5-310567号公报
【非专利文献1】J.C.Brown等，Canadian J Physiol Pharmacol 47：113-114，1969
【非专利文献2】J.M.Falko等，J Clin Endocrinol Metab 41(2)：260-265，1975
【非专利文献3】织田敏次等，消化管 功能与病态，1981年，中外医学社，P205-216
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发明内容
即，本发明涉及下述1)～7)的发明。
1)一种饮食后GIP分泌抑制剂，其特征在于，所述抑制剂以单酰甘油作为有效成分。
2)一种饮食后GIP分泌抑制方法，其特征在于，所述方法是摄取单酰甘油或将单酰甘油进行给药(administration)。
3)一种消化促进方法，其特征在于，所述方法是摄取单酰甘油或将单酰甘油进行给药。
4)一种胃积食的改善方法，其特征在于，所述方法是摄取单酰甘油或将单酰甘油进行给药。
5)单酰甘油作为食后GIP分泌抑制剂的用途。
6)单酰甘油作为消化促进剂的用途。
7)单酰甘油作为胃积食改善剂的用途。
具体实施方式
本发明涉及提供一种作为医药或食品有用的GIP分泌抑制剂。
本发明人等发现：单酰基甘油显著抑制食后GIP分泌，对促进消化和改善胃积食有用。
如果使用本发明的GIP分泌抑制剂，则可以使食后的GIP减少，可以促进消化吸收，可以实现改善胃积食等胃状态的改善。
作为单酰甘油，可以举出甘油的1位羟基被脂肪酸酯化而成的单酰甘油(1-单酰甘油)、2位羟基被脂肪酸酯化而成的单酰甘油(2-单酰甘油)、以及3位羟基被脂肪酸酯化而成的单酰甘油(3-单酰甘油)，其中，优选1-单酰甘油。脂肪酸残基的碳原子数没有特别限制，优选为8～24，特别优选为16～22。作为脂肪酸残基，可以举出饱和的脂肪酸残基和不饱和的脂肪酸残基，具体地说，可以举出如下酰基：来自辛酸、癸酸、月桂酸、肉豆蔻酸、棕榈酸、硬脂酸、油酸、亚油酸、亚麻酸、二十碳五烯酸、二十二碳六烯酸的酰基，或其混合物，以及来自从含有前述这些酸的牛油、猪油等动物油以及棕榈油、菜籽油、大豆油、红花油、玉米油、罗勒油、乌桕油(Sapium sebiferum oil)、亚麻子油、荏油等植物油衍生得到的脂肪酸等的酰基。这些单酰甘油可以使用一种或两种以上。
另外，在作为混合物使用该单酰甘油的情况下，不饱和脂肪酸残基的量优选为全部脂肪酸残基的55％以上，更优选70％以上，特别优选90％以上。进一步优选不饱和脂肪酸由油酸15～85％、亚油酸15～85％构成。最优选不饱和脂肪酸由油酸50～100％构成。此外，构成脂肪酸的含量是将构成酰基换算成脂肪酸而算出的。
本发明中使用的单酰甘油可以通过含有不饱和酰基的亚麻子油、荏胡麻油、罗勒油、大豆油、菜籽油等的水解反应、前述各种油脂与甘油的酯交换反应、来自这些油脂的脂肪酸和甘油的酯化反应等任意的方法得到。反应方法可以是利用碱催化剂等的化学反应法和利用脂肪酶等的酶的生化反应法中的任意一种。可以将得到的反应生成物分级而分离得到期望的单酰甘油。
如后述实施例所示，单酰甘油在与三酰甘油(以下也称作TAG)同时被摄取时，具有显著抑制GIP分泌量的增加的作用，该GIP分泌量的增加是由于葡萄糖和三酰甘油的摄取而造成的。因此，单酰甘油作为饮食后GIP分泌抑制剂，可以成为人或动物用食品或医药品或其原料。
另外，所谓“饮食后GIP分泌抑制”是指抑制来自消化管的GIP分泌量的增加，该来自消化管的GIP分泌量的增加是由于摄取了含有脂质和糖质的膳食、特别是含有较多脂质的膳食、以及其中含有较多三酰甘油的膳食而造成的。
本发明的饮食后GIP分泌抑制剂可以将本发明的单酰甘油以单体形式向人和动物给药，另外，也可以配合在各种饮食品、医药品、宠物食品等中来摄取。作为食品或饮料，可以作为以含有单酰甘油且具有促进消化或改善胃积食效果为特征并附有用于促进消化或改善胃积食的意思表示的饮料和食品而使用。另外，还可以应用于附有用于促进胃酸分泌、促进消化、改善胃积食等胃状态的改善的意思表示的美容食品、病人用食品、特定保健用食品等的食品或饮料。当作为医药品使用时，可以为，例如，锭剂、颗粒剂等经口用固体制剂，和内服液剂、糖浆剂等经口用液体制剂。
此外，在制备经口用固体制剂时，可以向本发明的单酰甘油中添加赋形剂，以及根据需要添加粘合剂、崩解剂、润滑剂、着色剂、矫味剂、矫嗅剂等后，按照常规方法来制造锭剂、覆膜锭剂、颗粒剂、散剂、胶囊剂等。另外，在制备经口用液体制剂时，可以添加矫味剂、缓冲剂、稳定化剂、矫味剂等，按照常规方法来制造内服液剂、糖浆剂、酏剂等。
上述各种剂型中单酰甘油的配合量通常为全部组合物中的0.1质量％以上，优选为1质量％以上，进一步优选为5重量％以上。
上述各种剂型的有效给药(摄取)量，对于单酰甘油而言，优选每1日为0.01～10g。另外，本发明的饮食后GIP分泌抑制剂在饭前·饭中·饭后使用有效果。
实施例
实施例1 单酰甘油的GIP分泌抑制作用
作为三酰甘油(TAG)使用三油酸甘油酯(triolein)，作为单酰甘油(MAG)使用1-甘油一油酸酯(1-monoolein)，进行下述实验。
使小鼠(C57BL/6J雄，8周龄)每1组12或14只，通过探针将如下物质进行经口给药：仅仅给予葡萄糖2mg/g体重，以及给予以0.02mg/g体重被蛋黄卵磷脂乳化的三油酸甘油酯2mg/g(分别为葡萄糖，TAG1)，或者给予在TAG1的乳化物中分别添加了0.08、0.2、0.4mg/g体重的1-甘油一油酸酯(分别为MAG1，MAG2，MAG3)的物质。乳化物的组成在表1中显示。10分钟后，经腹部大静脉采血，用ELISA法(Gastric Inhibitory Peptide EIA Kit，Phoenix Pharmaceutical Inc.)测定血中GIP。将没有给予乳化剂的小鼠血中的GIP值设定为初期值，10分钟后小鼠血中GIP增加量在表2中显示。
表1
| 乳化物组成 | 葡萄糖(mg/g体重) | 三油酸甘油酯(mg/g体重) | 1-甘油一油酸酯(mg/g体重) |
| 葡萄糖 | 2.0 | 0.0 | 0.0 |
| TAG1 | 2.0 | 2.0 | 0.0 |
| MAG1 | 2.0 | 2.0 | 0.08 |
| MAG2 | 2.0 | 2.0 | 0.2 |
| MAG3 | 2.0 | 2.0 | 0.4 |
表2
| 乳化物组成 | 小鼠血中GIP值(ng/mL) |
| 葡萄糖 | 0.6±0.1 (N＝12) |
| TAG1 | 1.5±0.2***(N＝12) |
| MAG1 | 1.3±0.2** (N＝14) |
| MAG2 | 1.2±0.1* (N＝14) |
| MAG3 | 1.0±0.2# (N＝14) |
相对于葡萄糖的TAG1、MAG1、MAG2的统计学上的显著性差异***：P<0.001，**：P<0.01，*：P<0.05
相对于TAG1的MAG3的统计学上的显著性差异#：P<0.05
与MAG的效果的浓度依赖性相关的统计学上的显著性差异：P<0.05
从表2的结果可知：摄取TAG时，与仅仅摄取葡萄糖相比，血中GIP增加。但是，当在TAG1中进一步添加了MAG(MAG1、MAG2、MAG3)时，可以在统计学上显著地浓度依赖性地抑制由于TAG而增加的GIP分泌量，从而显示出GIP分泌抑制效果。具体地说，例如，对于摄取了相对于TAG为五分之一的MAG的小鼠而言，与没有添加MAG的情况相比，血中GIP的增加量降低，从而抑制向血中分泌GIP的效果得到确认。
表3
表4
Claims (7)
1.一种饮食后GIP分泌抑制剂，其特征在于，
所述抑制剂以单酰甘油为有效成分。
2.一种饮食后GIP分泌抑制方法，其特征在于，
所述方法是摄取单酰甘油或将单酰甘油进行给药。
3.一种消化促进方法，其特征在于，
所述方法是摄取单酰甘油或将单酰甘油进行给药。
4.一种胃积食的改善方法，其特征在于，
所述方法是摄取单酰甘油或将单酰甘油进行给药。
5.单酰甘油作为饮食后GIP分泌抑制剂的用途。
6.单酰甘油作为消化促进剂的用途。
7.单酰甘油作为胃积食改善剂的用途。
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| PCT/JP2007/000364 WO2007122801A1 (ja) | 2006-04-24 | 2007-04-04 | Ｇｉｐ分泌抑制剤 |
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| CN103327836A (zh) * | 2010-12-29 | 2013-09-25 | 雅培制药有限公司 | 降低婴儿、幼儿或儿童的坏死性小肠结肠炎、腹痛和短肠综合征的发病率的方法 |
| CN103813790A (zh) * | 2011-09-15 | 2014-05-21 | 花王株式会社 | Gip上升抑制剂 |
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| US8283338B2 (en) * | 2007-11-30 | 2012-10-09 | Kao Corporation | GIP secretion inhibitor |
| JP2010222284A (ja) * | 2009-03-23 | 2010-10-07 | Kao Corp | 血中ｇｉｐ上昇抑制剤 |
| JP5576694B2 (ja) * | 2009-04-10 | 2014-08-20 | 花王株式会社 | Ｇｉｐ上昇抑制剤 |
| JP5328595B2 (ja) * | 2009-10-05 | 2013-10-30 | 花王株式会社 | Ｇｉｐ上昇抑制剤の評価又は選択方法 |
| JP5317919B2 (ja) * | 2009-10-05 | 2013-10-16 | 花王株式会社 | Ｇｉｐ上昇抑制剤の評価又は選択方法 |
| JP6026723B2 (ja) * | 2011-02-22 | 2016-11-16 | 花王株式会社 | Ｇｉｐ上昇抑制剤 |
| WO2018124011A1 (ja) | 2016-12-26 | 2018-07-05 | 花王株式会社 | 運動調節機能向上剤 |
| JP7158142B2 (ja) | 2016-12-26 | 2022-10-21 | 花王株式会社 | 低体温改善剤 |
| CN110087686A (zh) | 2016-12-26 | 2019-08-02 | 花王株式会社 | 认知功能改善剂 |
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| US5660842A (en) * | 1994-10-04 | 1997-08-26 | Bristol-Myers Squibb Company | Inhibition of helicobacter |
| US6762203B2 (en) * | 1999-08-03 | 2004-07-13 | Kao Corporation | Oil composition |
| JP2001064672A (ja) * | 1999-08-26 | 2001-03-13 | Kao Corp | 体脂肪燃焼促進剤 |
| KR20020093150A (ko) | 2000-05-16 | 2002-12-13 | 가부시키가이샤산와카가쿠켄큐쇼 | 인슐린 저항성 및/또는 비만 예방제 혹은 개선제 |
| JP5226912B2 (ja) * | 2000-06-12 | 2013-07-03 | 花王株式会社 | Ｐｐａｒ活性化剤 |
| DE60143753D1 (de) * | 2000-08-08 | 2011-02-10 | Kao Corp | Öl-/fett-zusammensetzung |
| JP4031219B2 (ja) * | 2000-08-08 | 2008-01-09 | 花王株式会社 | 油脂組成物 |
| JP4031218B2 (ja) * | 2000-08-08 | 2008-01-09 | 花王株式会社 | 油脂組成物 |
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| JP4824347B2 (ja) * | 2005-06-08 | 2011-11-30 | 花王株式会社 | Ｇｉｐ分泌抑制剤 |
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| CN103813790A (zh) * | 2011-09-15 | 2014-05-21 | 花王株式会社 | Gip上升抑制剂 |
| US10045957B2 (en) | 2011-09-15 | 2018-08-14 | Kao Corporation | GIP elevation inhibitor |
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