JP2011032237A - Composition containing low-molecule polysaccharide which has anti-obesity action, and composition using property of the same - Google Patents

Composition containing low-molecule polysaccharide which has anti-obesity action, and composition using property of the same Download PDF

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JP2011032237A
JP2011032237A JP2009181574A JP2009181574A JP2011032237A JP 2011032237 A JP2011032237 A JP 2011032237A JP 2009181574 A JP2009181574 A JP 2009181574A JP 2009181574 A JP2009181574 A JP 2009181574A JP 2011032237 A JP2011032237 A JP 2011032237A
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histidine
fat
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food
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Kazuyoshi Matsunaga
和義 松永
Kenji Akimoto
健志 秋元
Yoshio Shimizu
芳雄 清水
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Bizen Chemical Co Ltd
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    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A40/00Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
    • Y02A40/80Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in fisheries management
    • Y02A40/81Aquaculture, e.g. of fish
    • Y02A40/818Alternative feeds for fish, e.g. in aquacultures

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition which has an anti-obesity action and is used as a supplement. <P>SOLUTION: The composition prevents obesity of an animal and contains a low-molecule polysaccharide. The composition is ingested together with food or forage so as that weight ratio of the food or the forage ingested by the animal to the low-molecule polysaccharide is 1:130 to 20:80, comprises the polysaccharide having approximately 16 pieces of D-glucose, and has a helical structure regarding homoglucose chain of the approximately 6 pieces of D-glucose as a unit. Preferably, the composition contains histidine, a bonito extract and dietary fiber further. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

本発明は、抗肥満作用または抗肥満作用を増強する性質をもつ、螺旋構造を備えた低分子多糖類を含む組成物に関する。本発明はまた、この低分子多糖類の抗肥満作用または抗肥満作用を増強する性質を利用した組成物に関する。本発明さらに、これら組成物を用いた肥満を防ぐ方法に関する。   The present invention relates to a composition comprising a low-molecular-weight polysaccharide having a helical structure and having an anti-obesity effect or a property of enhancing anti-obesity effect. The present invention also relates to a composition utilizing the anti-obesity action or anti-obesity action of this low molecular weight polysaccharide. The present invention further relates to a method for preventing obesity using these compositions.

ヒスチジンを多く含むタンパク質、例えば、魚介類タンパク質が有する摂食抑制作用は、その作用機序の解明も進み、ヒスチジンが体内で代謝され誘導体化されて生じるヒスタミンが、ヒスタミンニューロンを活性化することにより過食予防に寄与するとされている(非特許文献1〜12)。   The anti-feeding action of proteins containing a large amount of histidine, for example, seafood proteins, is also elucidating the mechanism of action, and histamine produced by metabolism and derivatization of histidine in the body activates histamine neurons. It is said that it contributes to the prevention of overeating (Non-Patent Documents 1 to 12).

例えば、非特許文献1は、食事調査から、ヒスチジン高含有タンパク質が摂食量を抑制していることを示唆している。また、非特許文献2は、摂取されたヒスチジンが体内でヒスタミンに変換され、ヒスタミンニューロンを活性化することにより摂食抑制作用を示し、その傾向は女性の方が男性より顕著であったと記載している。非特許文献3は、BMIと体重当たりのヒスチジン摂取量との間に有意な負の相関があることを認めている。また、非特許文献4は、魚介類を摂取するとタンパク質摂取量当たりのヒスチジン摂取量が多くなり、正の相関関係が成立したことを認めている。非特許文献5は、体脂肪率の低い人ほどヒスチジン摂取量が多く、神経ヒスタミンを介した摂食抑制作用や脂肪分解作用によって体脂肪減少が起こり、肥満防止に繋がることを報告している。非特許文献6は、カゼイン、煮干しとあこや貝を与えた1週間のラット飼育結果から、ヒスチジンリッチの煮干しを与えた場合、体重増加が相対的に最も少なかったと報告している。非特許文献7は、ヒスチジン食(ヒスチジン4g/kg)とアルギニン食(アルギニン4g/kg)によるラット飼育実験から、体内に吸収されたヒスチジンが約1日で摂食抑制作用を示すことを報告している。非特許文献8は、ヒスチジン食(ヒスチジン4g/kg)とアルギニン食(アルギニン4g/kg)によるラット飼育実験から、飼料摂取量に有意差は認められないにもかかわらず、肝臓組織中の中性脂肪量がヒスチジン飼料群で有意に低い値を示したことから、ヒスチジンはエネルギー消費を亢進している可能性があることを記載している。非特許文献9は、ヒスタミンが摂食抑制作用を発現する濃度が、29mg/g飼料であると報告している。非特許文献10は、カツオ熱水抽出物を添加した飼料(ヒスタミン37mg/g)による摂食抑制および脂肪分解の促進を実証している。   For example, Non-Patent Document 1 suggests that high histidine-containing protein suppresses food intake from dietary surveys. Non-Patent Document 2 describes that ingested histidine is converted into histamine in the body and activates histamine neurons to show an eating suppression effect, and the tendency is more pronounced in women than in men. ing. Non-Patent Document 3 recognizes that there is a significant negative correlation between BMI and histidine intake per body weight. Further, Non-Patent Document 4 recognizes that when consuming seafood, the histidine intake per protein intake increases and a positive correlation is established. Non-Patent Document 5 reports that the lower the body fat percentage, the higher the histidine intake, and the reduction of body fat occurs due to the feeding suppression action and lipolysis action via nerve histamine, leading to obesity prevention. Non-Patent Document 6 reports that the weight gain was relatively minimal when histidine-rich boiled was given, based on the results of one-week rat breeding with casein, boiled and dried oysters. Non-patent document 7 reports that histidine absorbed in the body shows an antifeeding effect in about one day from a rat breeding experiment with a histidine diet (histidine 4 g / kg) and an arginine diet (arginine 4 g / kg). ing. Non-patent document 8 shows that, from a rat breeding experiment with a histidine diet (histidine 4 g / kg) and an arginine diet (arginine 4 g / kg), neutrality in liver tissue was observed, although no significant difference was observed in feed intake. Since the amount of fat showed a significantly low value in the histidine feed group, it is described that histidine may promote energy consumption. Non-Patent Document 9 reports that the concentration at which histamine develops an antifeedant action is 29 mg / g feed. Non-Patent Document 10 demonstrates the suppression of feeding and the promotion of lipolysis by a feed supplemented with a bonito hot water extract (histamine 37 mg / g).

中島滋、濱田稔ほか:低エネルギー摂取者に観察されたヒスチジン高含有タンパク質摂取による摂食抑制、日栄・食糧会誌 2000、53:207−214.Nakajima Shigeru, Tomita Kaoru et al .: Inhibition of eating by high histidine-containing protein observed in low-energy intakes, Nichiei / Food Journal 2000, 53: 207-214. 中島滋、田中香ほか:瀬戸内海浜地区の女性におけるエネルギー摂取量とヒスチジン摂取量との相関、肥満研究 2001、7:276−282.Nakajima Shigeru, Tanaka Kaoru et al: Correlation between energy intake and histidine intake in women in the Seto Inland Sea area, obesity study 2001, 7: 276-282. 辻真紀子、中島滋ほか:BMIとヒスチジン摂取量との相関、肥満研究 2002、8:302−305.Makiko Tsuji, Shigeru Nakajima et al .: Correlation between BMI and histidine intake, obesity study 2002, 8: 302-305. 中島滋、田中香ほか:タンパク質を供給する食品群別にみたヒスチジン摂取量に関する調査研究、肥満研究 2004、10:66−72.Nakajima Shigeru, Tanaka Kaoru et al .: Research study on histidine intake by food group supplying protein, obesity study 2004, 10: 66-72. 辻真紀子、笠岡誠一ほか:体脂肪率と体重当たりのヒスチジン摂取量との相関、肥満研究 2004、10:173−176.Makiko Tsuji, Seiichi Kasaoka et al .: Correlation between body fat percentage and histidine intake per body weight, obesity study 2004, 10: 173-176. 中島滋、濱田稔ほか:Inhibitory effect of niboshi on food intake.Fishers Science 2000、66:795−797.Nakajima Shigeru, Satoshi Hamada et al .: Inhibitory effect of niboshi on food intake. Fishers Science 2000, 66: 795-797. 中島滋、笠岡誠一ほか:カフェテリア方式を用いたヒスチジン添加飼料によるラットの摂食抑制作用、肥満研究 2002、8:55−60.Nakajima Shigeru, Kasaoka Seiichi et al .: Antifeedant action of rats with histidine-added diet using the cafeteria method, obesity study 2002, 8: 55-60. 笠岡誠一、中島滋ほか:ヒスチジン添加飼料によるラット肝組織の中性脂肪低下作用、肥満研究 2002、8:168−172.Seiichi Kasaoka, Shigeru Nakajima et al .: Neutral fat lowering effect of rat liver tissue by diet containing histidine, obesity study 2002, 8: 168-172. Kasaoka S.Kasaoka Tら:Histidine supplementation suppresses food intake and fat accumulation in rats.Nutrition 2004、20:991−996.Kasaoka S .; Kasaoka T et al .: Histidene supplementation supplements food intake and fat accumulation in rats. Nutrition 2004, 20: 991-996. 笠岡誠一、鍋島美佳ほか:カツオ節製造工程で得られたヒスチジン高含有物質の摂食抑制および脂肪分解促進、肥満研究 2005、1:63−68.Seiichi Kasaoka, Mika Nabeshima et al .: Suppressing eating and promoting lipolysis of histidine-rich substances obtained in the bonito production process, obesity study 2005, 1: 63-68.

上記のような過食予防効果にもかかわらず、ヒスチジンは、体内に摂取されると、代謝を受けてヒスタミンに変換され、ヒスタミンが過剰になればアレルギー症状を発現し、過剰のヒスタミンとアレルギー症状発現との間には有意な相関があることが示されている。従って、ヒスチジンの過剰摂取を避けると同時にヒスチジンを利用した過食予防効果を得ることが望まれる。   Despite the above effects of preventing overeating, histidine is metabolized and converted to histamine when ingested by the body. If histamine is excessive, allergic symptoms are manifested, and excessive histamine and allergic symptoms are manifested. It is shown that there is a significant correlation with. Therefore, it is desired to avoid the excessive intake of histidine and at the same time obtain the effect of preventing overeating using histidine.

本発明は、上記のヒスチジンの過剰摂取に付随する課題を解決するために、例えばデンプンから調製される、螺旋構造を備える低分子多糖類を利用する。本発明者らは、特定の螺旋構造を備える低分子多糖類が、抗肥満作用または抗肥満作用を増強する性質を有することを見出し、本発明を完成するに至った。この低分子多糖類は、それ自体抗肥満作用を有するとともに、ヒスチジンとともに存在することによって互いのもつ抗肥満作用を相乗的に増大する。   The present invention utilizes a low-molecular-weight polysaccharide having a helical structure prepared from, for example, starch, in order to solve the above-mentioned problems associated with overdose of histidine. The present inventors have found that a low-molecular-weight polysaccharide having a specific helical structure has an anti-obesity action or a property of enhancing the anti-obesity action, and has completed the present invention. This low-molecular-weight polysaccharide itself has an anti-obesity effect, and synergistically increases each other's anti-obesity effect by being present with histidine.

より特定すれば、本発明は以下の項目に関し得る。
(項目1)動物の肥満を防ぐための組成物であって、低分子多糖類を含み、上記組成物は、上記動物が摂取する食品または飼料と上記低分子多糖類との重量比が1:130〜20:80の割合になるように上記食品または飼料とともに摂取され、上記低分子多糖類が約16個のD−グルコースからなり、かつ約6個のD−グルコースのホモグルコース鎖を単位とする螺旋構造をもつ、組成物。
(項目2)さらにヒスチジン、カツオ抽出物または食物繊維を含む、項目1に記載の組成物。
(項目3)上記ヒスチジンと上記低分子多糖類とを、約1:10〜約1:127の割合の重量比で含む、項目2に記載の組成物。
(項目4)上記低分子多糖類と上記食物繊維とを、約1:1の重量比で含む、項目2に記載の組成物。
(項目5)錠剤、顆粒カプセル製剤およびクッキーからなる群から選択される形態である、項目1〜4のいずれか1項に記載の組成物。
More specifically, the present invention can relate to the following items.
(Item 1) A composition for preventing obesity in an animal, comprising a low molecular weight polysaccharide, wherein the composition has a weight ratio of food or feed consumed by the animal and the low molecular weight polysaccharide of 1: Ingested with the food or feed in a ratio of 130 to 20:80, the low-molecular polysaccharide is composed of about 16 D-glucose, and about 6 D-glucose homoglucose chains as a unit. A composition having a helical structure.
(Item 2) The composition according to item 1, further comprising histidine, bonito extract or dietary fiber.
(Item 3) The composition according to item 2, comprising the histidine and the low molecular weight polysaccharide in a weight ratio of about 1:10 to about 1: 127.
(Item 4) The composition according to item 2, comprising the low molecular weight polysaccharide and the dietary fiber in a weight ratio of about 1: 1.
(Item 5) The composition according to any one of Items 1 to 4, which is a form selected from the group consisting of tablets, granule capsule preparations, and cookies.

上記低分子多糖類は、約16個のD−グルコースからなり、約3、000の分子量を有し、約6個のD−グルコースのホモグルコース鎖を単位とする螺旋構造を備えるホモグルコース体であって、水溶性であり、例えば、デンプンから調製され得る。   The low-molecular-weight polysaccharide is a homoglucose body comprising about 16 D-glucose, having a molecular weight of about 3,000, and having a helical structure having a unit of about 6 D-glucose homoglucose chains. It is water soluble and can be prepared, for example, from starch.

好ましくは、上記低分子多糖類は、螺旋の1巻きがD−グルコース残基6個からなる右巻き螺旋構造を有し得、その結果、その螺旋の中央にヨウ素分子Iが取り込まれてヨウ素呈色反応で発色するような構造を有している。このような低分子多糖類は、例えば、備前化成株式会社(岡山県赤磐市徳富363)からポタコーゲン(登録商標)として市販され入手可能である。 Preferably, the low molecular weight polysaccharide may have a right-handed spiral structure in which one turn of the spiral is composed of 6 D-glucose residues, and as a result, iodine molecule I 3 is incorporated into the center of the spiral to form iodine. It has a structure that develops color by a color reaction. Such a low-molecular-weight polysaccharide is commercially available as, for example, Potacogen (registered trademark) from Bizen Kasei Co., Ltd. (363 Tokutomi, Akamine, Okayama Prefecture).

本発明によれば、ヒスチジンと、螺旋構造を有する低分子多糖体、代表的にはポタコーゲン(登録商標)との組み合わせによって、従来知られている摂食抑制を発現し、抗肥満作用を得るためのヒスチジンの使用量の低減化を可能とし、かつ同時に動物の組織の脂肪量を相乗的に低減することができる。   According to the present invention, a combination of histidine and a low-molecular-weight polysaccharide having a helical structure, typically Potacogen (registered trademark), exhibits a known anti-feeding effect and obtains an anti-obesity effect. The amount of histidine used can be reduced, and at the same time, the fat content of animal tissues can be reduced synergistically.

このポタコーゲン(登録商標)は、体重増加作用があることが知られるフルクトースを利用したフルクトース負荷ラットにおいても、動物の皮下脂肪低下作用(下腹部皮下脂肪;19%低下、腹腔内脂肪;24%低下)を示すことが明らかとなり、ヒスチジンとポタコーゲン(登録商標)との併用により、抗肥満作用を得るためのヒスチジンの使用量の低減化とともに、動物の皮下脂肪を相乗的に低減する効果を期待できる。また同様に、ポタコーゲン(登録商標)は、おからなどの食物繊維と組み合わせることにより動物の皮下脂肪量または体脂肪量を相乗的に減少する作用を期待できる。従って、本発明をヒトおよびペットを含む動物に応用して、肥満解消に役立てることができる。   This Potacogen (registered trademark) is also effective in reducing the subcutaneous fat of animals (lower abdominal subcutaneous fat; 19% lower, intraperitoneal fat; 24% lower) even in fructose-loaded rats using fructose, which is known to have a weight gain effect ), And the combined use of histidine and Potacogen (registered trademark) can be expected to reduce the amount of histidine used to obtain an anti-obesity effect and synergistically reduce the subcutaneous fat of animals. . Similarly, Potacogen (registered trademark) can be expected to act synergistically to reduce the amount of subcutaneous fat or body fat in animals by combining with dietary fiber such as okara. Therefore, the present invention can be applied to the elimination of obesity by applying it to animals including humans and pets.

本発明の水溶性多糖類は、それ自体が抗肥満作用を有し、さらに、ヒスチジンと併用することによって、抗肥満効果を得るために必要なヒスチジンの使用量を低減し、体脂肪を相乗的に低減する。本発明によれば、この水溶性多糖類を用いて、抗肥満作用が増強された複合製剤または食品組成物が製造される。   The water-soluble polysaccharide of the present invention itself has an anti-obesity action, and further, when used in combination with histidine, reduces the amount of histidine used to obtain an anti-obesity effect and synergizes body fat. To reduce. According to the present invention, a composite preparation or food composition with enhanced anti-obesity action is produced using this water-soluble polysaccharide.

本発明により、抗肥満作用のあるヒスチジンとポタコーゲン(登録商標)との組み合わせにより相乗作用を発現して、抗肥満作用を得るためのそれぞれの成分の使用量を低減して、体脂肪減少作用を示す錠剤、顆粒カプセル製剤またはクッキーなどのパン・菓子類を製造する方法で、ヒトおよびペットなどに適用して健康維持に役立て得る。   According to the present invention, a combination of anti-obesity histidine and Potacogen (registered trademark) produces a synergistic effect, reducing the amount of each component used to obtain the anti-obesity effect, and reducing body fat. The method for producing breads and confectionery such as tablets, granule capsule preparations or cookies shown can be applied to humans and pets to help maintain health.

本発明により、ヒスチジンの体脂肪減少作用を相乗的に増強するために、低分子多糖類とヒスチジン、またはおからなどの食物繊維とを含む食品組成物を提供し得る。   According to the present invention, in order to synergistically enhance the body fat reducing action of histidine, a food composition comprising a low-molecular polysaccharide and dietary fiber such as histidine or okara can be provided.

本発明の組成物の抗肥満作用を示す図である。図に示されるグラフの縦軸は、実験に用いたラットの下腹部皮下脂肪含量を表し、図の横軸は実験群を表し、図中左から、普通群、対照群、試験対照群、PoG群をそれぞれ示す。It is a figure which shows the anti-obesity effect of the composition of this invention. The vertical axis of the graph shown in the figure represents the lower abdominal subcutaneous fat content of the rats used in the experiment, and the horizontal axis of the figure represents the experimental group. From the left in the figure, the normal group, control group, test control group, PoG Each group is shown. 本発明の組成物の抗肥満作用を示す図である。図に示されるグラフの縦軸は、実験に用いたラットの腹腔内白色脂肪含量を表し、図の横軸は実験群を表し、図中左から、普通群、対照群、試験対照群、PoG群をそれぞれ示す。It is a figure which shows the anti-obesity effect of the composition of this invention. The vertical axis of the graph shown in the figure represents the intraperitoneal white fat content of the rats used in the experiment, and the horizontal axis of the figure represents the experimental group. From the left in the figure, the normal group, the control group, the test control group, PoG Each group is shown.

本明細書で用いる用語「抗肥満作用」は、食物もしくは飼料、または食物もしくは飼料の一部として動物に摂取された場合、この動物の摂食量を適正に抑制し、その結果として、この動物の体重の増加を抑制または減少する作用、またはこの動物の体脂肪または組織の皮下脂肪含量を増加を抑制または減少する作用をいう。本発明の組成物は、通常、摂取される飼料または食物のサプリメント(本明細書では「食品類または食品添加物類」とも称される)として摂取され得る。   The term “anti-obesity effect” as used herein, when taken by an animal as food or feed, or as part of food or feed, properly controls the animal's food intake and, as a result, It refers to an action that suppresses or decreases the increase in body weight, or an action that suppresses or decreases the increase in the body fat or the subcutaneous fat content of tissues of this animal. The composition of the present invention can be ingested usually as an ingestible feed or food supplement (also referred to herein as “foods or food additives”).

好ましくは、本発明の組成物は、摂取される飼料または食物のサプリメントとして用いられ、この組成物は、上記動物が摂取する食品または飼料と該低分子多糖類との重量比が1:130〜20:80の割合になるように該食品または飼料とともに摂取される。   Preferably, the composition of the present invention is used as a feed or food supplement to be ingested, and the composition has a weight ratio of food or feed to be consumed by the animal and the low molecular weight polysaccharide of from 1: 130 to Ingested with the food or feed at a ratio of 20:80.

好ましくは、本発明の組成物は、上記ヒスチジンと上記低分子量多糖類とを、約1:5〜約1:127の重量比の割合で含み、さらに好ましくは、本発明の組成物は、上記ヒスチジンと上記低分子量多糖類とを、約1:10重量比の割合で含む。   Preferably, the composition of the present invention comprises the histidine and the low molecular weight polysaccharide in a weight ratio of about 1: 5 to about 1: 127, more preferably the composition of the present invention comprises It contains histidine and the low molecular weight polysaccharide in a ratio of about 1:10 weight ratio.

また好ましくは、本発明の組成物は、上記低分子量多糖類と上記カツオ抽出物または食物繊維とを、約1:2〜2:1の範囲の重量比の割合で含み、さらに好ましくは、本発明の組成物は、上記低分子量多糖類と上記カツオ抽出物または食物繊維とを、約1:1の重量比の割合で含む。なお、本明細書で%について言及する場合、特に指定がなければ、重量%を意味する。   Also preferably, the composition of the present invention comprises the low molecular weight polysaccharide and the bonito extract or dietary fiber in a proportion by weight ratio ranging from about 1: 2 to 2: 1, more preferably The composition of the invention comprises the low molecular weight polysaccharide and the bonito extract or dietary fiber in a weight ratio of about 1: 1. In addition, when mentioning% in this specification, unless otherwise specified, it means weight%.

本発明の組成物が適用される上記「動物」は、制限されずに、霊長類、哺乳類、は虫類、両生類または鳥類に属する動物、ペット動物、家畜類などを含む。   The “animal” to which the composition of the present invention is applied includes, without limitation, primates, mammals, reptiles, amphibians or birds, pet animals, livestock and the like.

本発明の組成物の抗肥満作用を示すに有効な量は、適切な哺乳動物モデルによって容易に確認され得る。次に、このような情報を用いて、さらにはヒトにおける摂取に有用な量を決定し得る。ヒトにおける「抗肥満作用を示すに有効な量」は、例えば、本明細書に記載されるラットを用いた実験に準じて容易に決定され得る。または、本発明の組成物は、有害成分を含まないので、ヒトにおける「抗肥満作用を示すに有効な量」はヒトに摂取されて容易に確認され得る。   An effective amount of the anti-obesity effect of the composition of the present invention can be readily ascertained by a suitable mammalian model. Such information can then be used to determine further useful amounts for ingestion in humans. The “effective amount for exhibiting an anti-obesity effect” in humans can be easily determined according to, for example, experiments using rats described in the present specification. Alternatively, since the composition of the present invention does not contain harmful components, the “effective amount for showing an anti-obesity effect” in humans can be easily confirmed by ingestion by humans.

実際に飼料または食物とともに摂取されて抗肥満作用を示す上記低分子多糖類、上記低分子多糖類、およびヒスチジン、カツオ抽出物または食物繊維の量は、適用される個体の体重、健康状態などに依存し得、抗肥満作用が最適に達成されるように調整され得る。   The amount of the low molecular weight polysaccharide, the low molecular weight polysaccharide, and the histidine, bonito extract or dietary fiber, which are actually taken with feed or food and exhibit anti-obesity action, depends on the weight, health condition, etc. of the applied individual. And can be adjusted so that the anti-obesity effect is optimally achieved.

上記錠剤、顆粒カプセル製剤は、打錠加工助剤、顆粒加工助剤、カプセル加工助剤を用いて調製され得る。   The tablet and granule capsule preparation can be prepared using a tableting aid, granule aid, and capsule aid.

本明細書で用いられる用語「打錠加工助剤」は、制限されずに、グラニュー糖、上白糖、粉糖、還元麦芽糖水飴粉末、乳糖、ブドウ糖、プルラン、エリスリトール、デンプン、デキストリンなどあらゆる糖類、結晶セルロース、アラビアガム、おからなどの食物繊維類、トウモロコシタンパク、リン酸カルシウムなどの食品カルシウム、食品エキス類、食品乾燥粉末類、天然果汁末類、ショ糖脂肪酸エステルなどの界面活性剤、粉末油脂類、グリセリン、脂肪酸エステルなどの油脂類、またはチュワブル錠(食べる錠剤)に使用する各種甘味料、各種酸味料、各種香料などの味付け素材、コーティング素材またはとしてのシェラック、トウモロコシタンパク、酵母細胞壁、デンプン、還元麦芽糖水飴、シュガーレス糖衣、マルチトール、グリセリン、ソルビトール、HPMC、HPCを含む。   The term “tablet processing aid” used in the present specification is not limited, and includes any sugars such as granulated sugar, super white sugar, powdered sugar, reduced maltose starch syrup, lactose, glucose, pullulan, erythritol, starch, dextrin, Dietary fibers such as crystalline cellulose, gum arabic, and okara, food calcium such as corn protein and calcium phosphate, food extracts, food dried powders, natural fruit juice powders, surfactants such as sucrose fatty acid esters, powdered fats and oils , Oils and fats such as glycerin, fatty acid esters, etc., various sweeteners used in chewable tablets (eating tablets), various acidulants, various flavoring materials such as fragrances, coating materials or shellac, corn protein, yeast cell wall, starch, Reduced maltose starch syrup, sugarless sugar coating, maltitol, guri Including phosphorus, sorbitol, HPMC, the HPC.

本明細書で用いられる用語「顆粒加工助剤」は、制限されずに、グラニュー糖、上白糖、粉糖、還元麦芽糖水飴粉末、乳糖、ブドウ糖、プルラン、エリスリトール、デンプン、デキストリンなどあらゆる糖類、結晶セルロース、アラビアガムなどの食物繊維類、トウモロコシタンパク、リン酸カルシウムなどの食品カルシウム、食品エキス類、食品乾燥粉末類、天然果汁末類を含む。   The term “granular processing aid” used in the present specification is not limited, and includes any sugar, crystals such as granulated sugar, super white sugar, powdered sugar, reduced maltose starch syrup, lactose, glucose, pullulan, erythritol, starch, and dextrin. Includes dietary fibers such as cellulose and gum arabic, food calcium such as corn protein and calcium phosphate, food extracts, food dry powders, and natural fruit juice powders.

本明細書で用いられる用語「カプセル加工助剤」は、制限されずに、ハードカプセルタイプのカプセルを調製するための、グラニュー糖、上白糖、粉糖、還元麦芽糖水飴粉末、乳糖、ブドウ糖、プルラン、エリスリトール、デンプン、デキストリンなどあらゆる糖類、結晶セルロース、アラビアガムなどの食物繊維類、トウモロコシタンパク、リン酸カルシウムなどの食品カルシウム、食品エキス類、食品乾燥粉末類、天然果汁末類を、そしてソフトカプセルタイプのカプセルを調製するための、食品油脂、ミツロウ、グリセリン脂肪酸エステルなどの内容物粘度調整剤を含む。   The term “capsule processing aid” as used herein is not limited, and is used to prepare hard capsule type capsules, granulated sugar, super white sugar, powdered sugar, reduced maltose starch syrup, lactose, glucose, pullulan, All sugars such as erythritol, starch, dextrin, dietary fibers such as crystalline cellulose and gum arabic, food calcium such as corn protein and calcium phosphate, food extracts, dried food powders, natural fruit juices, and soft capsule type capsules It contains content viscosity modifiers such as food fats and oils, beeswax and glycerin fatty acid esters for preparation.

打錠製剤は、通常、打錠機を使用して調製される。そして打錠製剤に味付け素材をブレンドしてチュワブル錠にしたり、錠剤表面を自動コーティング機、噴霧顆粒機または手掛けパンを用いてコーティングされる。顆粒製剤の成形には、噴霧顆粒機タイプ、練りだし(押し出し)タイプまたは高速撹拌顆粒機タイプの各種顆粒機が使用され得る。カプセル製剤の調製には、カプセル助剤を混合してカプセル充填機(ハードタイプおよびソフトタイプ)が使用され得る。   A tableting formulation is usually prepared using a tableting machine. A tableting preparation is blended with a seasoning material to form a chewable tablet, or the tablet surface is coated using an automatic coating machine, a spray granulator or a hand pan. Various granulators of the spray granulator type, the kneading (extruding) type, or the high-speed stirring granulator type can be used for forming the granule preparation. For preparation of capsule preparation, capsule filling machines (hard type and soft type) can be used by mixing capsule aids.

本発明を、以下の記載の実施例を用いて説明する。以下の実施例は、本発明を制限する意図はなく、本発明の単なる例示に過ぎない。   The invention is illustrated using the examples described below. The following examples are not intended to limit the invention, but are merely illustrative of the invention.

(実施例1)低分子多糖類の抗肥満効果
1.検体、飼料および動物
MF標準飼料(オリエンタル酵母工業(株))にポタコーゲン(登録商標)20%を添加して検体とした。SD系ラット(雌性、7週齢)は、日本チャールズ・リバー(株))から購入した。
Example 1 Anti-obesity effect of low molecular weight polysaccharide
1. Sample, feed, and animal MF standard feed (Oriental Yeast Industry Co., Ltd.) were added with 20% Potacogen (registered trademark) to prepare a sample. SD rats (female, 7 weeks old) were purchased from Nippon Charles River Co., Ltd.).

2.実験方法
1群6匹のSD系メスラットを3群用意した。対照群およびポタコーゲン(登録商標)投与群(実験群)には25%フルクトース水溶液を、正常群には水道水を飲料水として4週間自由摂取させた。その間、実験群には20%ポタコーゲン(登録商標)含有飼料を、対照群および正常群には標準飼料を自由に摂取させた。
2. Experimental Method Three groups of 6 SD female rats were prepared. The control group and Potacogen (registered trademark) administration group (experimental group) were allowed to freely take a 25% fructose aqueous solution and the normal group as tap water for 4 weeks. Meanwhile, 20% Potacogen (registered trademark) -containing diet was freely given to the experimental group, and a standard diet was freely given to the control group and normal group.

3.実験結果
飼育開始15日以降は実験群の体重は、対照群に比較して僅かに減少傾向を示した。対照群と実験群は、27日間の飼育期間におけるラット一匹当たりの一日平均攝餌量は9.27gで、約14gであった正常群の一日平均攝餌量より少なかった。また、フルクトースの一日平均摂取量は、対照群では実験群よりやや高めに推移したものの、23〜25mL/日/匹であった。
3. Experimental Results From the 15th day after the start of breeding, the body weight of the experimental group showed a slightly decreasing tendency compared to the control group. In the control group and the experimental group, the average daily diet per rat during the 27-day breeding period was 9.27 g, which was less than the average daily diet of the normal group, which was about 14 g. The average daily intake of fructose was 23-25 mL / day / animal although the control group was slightly higher than the experimental group.

実験最終日にラットを犠牲にし、下腹部皮下脂肪および腹腔内脂肪を摘出してこれらの重量を測定比較した。その結果、対照群と比較して実験群では、下腹部皮下脂肪が24.8%、そして腹腔内白色脂肪が19.3%少なかった。この結果より、ポタコーゲン(登録商標)は、体重増加作用のあることが知られるフルクトースの存在下でも、体重減少作用および皮下脂肪含量を減少する作用を示し、抗肥満効果を有することが明らかとなった。   On the final day of the experiment, the rats were sacrificed, and the lower abdominal subcutaneous fat and intraperitoneal fat were removed and their weights were measured and compared. As a result, the experimental group had 24.8% lower abdominal subcutaneous fat and 19.3% less intraperitoneal white fat than the control group. From this result, it is clear that Potacogen (registered trademark) has an anti-obesity effect, exhibiting a weight-reducing action and an action to reduce subcutaneous fat content even in the presence of fructose, which is known to have a weight-gaining action. It was.

(実施例2)
1.検体、飼料および動物
ポタコーゲン(登録商標)50%、L−ヒスチジン5%、L−シトルリン7.5%、粉末マビット50M 35.5%、シュガーエステル1%および第三リン酸カルシウム1%配合の粉末(以下、PoG−His配合末という。)を作製して検体とした。
(Example 2)
1. Sample, feed and animal Potacogen (registered trademark) 50%, L-histidine 5%, L-citrulline 7.5%, powder Mabit 50M 35.5%, sugar ester 1% and tribasic calcium phosphate 1% , PoG-His blended powder) was prepared and used as a specimen.

高脂肪高ショ糖食(牛脂、ラードなどの脂肪含量30%、オリエンタル酵母工業(株))、MF標準飼料(オリエンタル酵母工業(株))およびSD系メスラット(7週齢、日本チャールズ・リバー(株))をそれぞれ購入して準備した。   High fat high sucrose diet (beef tallow, lard fat content 30%, Oriental Yeast Co., Ltd.), MF Standard Feed (Oriental Yeast Industry Co., Ltd.) and SD female rats (7 weeks old, Charles River Japan ( Co.)) was purchased and prepared.

2.実験方法
SD系メスラットを4群(各5匹)に分け、対照群には高脂肪高ショ糖食餌を、試験対照群にはラットMF標準飼料を10%となるように高脂肪高ショ糖食餌に混合した餌を、PoG群として検体であるPoG−His配合末を高脂肪高ショ糖食餌に10%混合した餌を、そして普通群としてラットMF標準飼料をそれぞれ自由摂取させ、下記の項目(1〜4)について試験した。PoG群の餌1g中にはポタコーゲン(登録商標)50mg、L−ヒスチジン5mgが含まれている。
(1)体重を、実験開始日と実験開始後3日間おきに連続39日間測定した。
(2)実験最終日に、ラットを犠牲にして下腹部皮下脂肪、腹腔内白色脂肪を摘出し、これらの脂肪を測定した。
(3)各群の餌摂取量は、実験開始前一週間から実験終了までに三日間おきにラット一匹当たりの平均摂取量を算出した。
(4)統計解析は、平均値の差の検定をDunnett,t−試験により行い、p<0.05、p<0.01をそれぞれ有意差あり*、**とした。
2. Experimental Method SD female rats were divided into 4 groups (5 each), high fat high sucrose diet for the control group and high fat high sucrose diet for the test control group so that the rat MF standard diet was 10%. As a PoG group, 10% of a PoG-His compound powder mixed with a high-fat and high-sucrose diet was fed as a PoG group, and a rat MF standard diet as a normal group, and the following items ( 1-4) were tested. In 1 g of feed of the PoG group, 50 mg of Potacogen (registered trademark) and 5 mg of L-histidine are contained.
(1) Body weight was measured for 39 consecutive days every 3 days after the start of the experiment and after the start of the experiment.
(2) On the last day of the experiment, the lower abdominal subcutaneous fat and intraperitoneal white fat were excised at the sacrifice of the rat, and these fats were measured.
(3) As the food intake of each group, the average intake per rat was calculated every three days from one week before the start of the experiment to the end of the experiment.
(4) Statistical analysis was performed by Dunnett, t-test for the difference between the mean values, and p <0.05 and p <0.01 were significant differences * and **, respectively.

3.結果
高脂肪高ショ糖食投与群(対照群)のラットは、39日間の飼育によって、MF標準飼料投与群(普通群)のラットと比較して、平均で2.5倍以上の体重増加を示した。そして10%MF標準飼料を添加した高脂肪高ショ糖食投与群(試験対照群)は、高脂肪高ショ糖食投与群(対照群)より平均体重が約11%減少したにもかかわらず、10%PoG−His配合末添加の高脂肪高ショ糖食投与群(PoG群)では約26%の体重減少を認めた。
3. Results Rats in the high-fat high-sucrose diet group (control group) gained an average weight gain of 2.5 times or more on average compared to rats in the MF standard diet group (normal group) by breeding for 39 days. Indicated. And the high fat high sucrose diet administration group (test control group) to which 10% MF standard feed was added, although the average body weight was reduced by about 11% from the high fat high sucrose diet administration group (control group), About 26% weight loss was observed in the high fat high sucrose diet administration group (PoG group) added with 10% PoG-His.

その体重減少の中身として体脂肪含量を調べた結果次のようであった。すなわち、PoG群の下腹部皮下脂肪含量は、試験対照群のそれより平均で約34%減少していた(図1)。また、PoG群の腹腔内白色脂肪含量は試験対照群のそれより平均で約48%減少していた(図2)。このようにPoG−His配合末添加の高脂肪高ショ糖食投与により、ラット下腹部皮下脂肪および腹腔内白色脂肪の増加を有意に減少させることが明らかとなった。ラットの餌の1日平均摂取量は普通群で約16.4gであり、その一方、対照群と試験対照群実験群の2群のいずれとも約14gであり、高脂肪高ショ糖食餌群では摂食抑制作用が認められた。これはMF標準飼料より高脂肪高ショ糖食の方が高エネルギーであることによると考えられる。   As a result of examining the body fat content as the contents of the weight loss, it was as follows. That is, the lower abdominal subcutaneous fat content of the PoG group was reduced by about 34% on average from that of the test control group (FIG. 1). In addition, the intraperitoneal white fat content in the PoG group decreased by about 48% on average from that in the test control group (FIG. 2). Thus, it was clarified that administration of a high-fat high-sucrose diet added with a PoG-His compound powder significantly reduced the increase in rat lower abdominal subcutaneous fat and intraperitoneal white fat. The average daily intake of rat food is about 16.4 g in the normal group, while it is about 14 g in both the control group and the experimental group of the test control group. In the high fat high sucrose diet group, Antifeedant effect was observed. This is probably because the high-fat and high-sucrose diet has higher energy than the MF standard feed.

(実施例3)
1.検体、飼料および動物
クッキーの基剤として薄力粉24.47%、砂糖10%、無塩バター31.55%、甘味料(ステビア)0.1%、トレハロース5.62%、全卵5.26%、デキストリン3.85%を混合した。別にポタコーゲン(登録商標)とカツオ抽出物(ヒスチジン含有:以下に記載のように調製した。)、および、おから(スーパーマーケットなどで市販されているもの)を150:75:150の比率で混合したサンプルAとポタコーゲン(登録商標)とおからを150:150の比率で混合したサンプルBを調整した。サンプルAおよびサンプルBのそれぞれを、上述の基剤に19.15%添加して全体として100%となったものをそれぞれサンプルIおよびサンプルIIのクッキーとして作製した。
(Example 3)
1. Analyte, 24.47% flour as a base feed and animal cookies, 10% sugar, unsalted butter 31.55%, sweetener (stevia) 0.1%, trehalose 5.62%, whole eggs 5.26% , 3.85% dextrin was mixed. Separately, Potacogen (registered trademark) and bonito extract (containing histidine: prepared as described below) and okara (commercially available at supermarkets, etc.) were mixed at a ratio of 150: 75: 150. Sample B was prepared by mixing sample A, Potacogen (registered trademark) and okara in a ratio of 150: 150. Samples A and B were each made into a cookie of Sample I and Sample II by adding 19.15% to the above-mentioned base to give a total of 100%.

−カツオ抽出物の調製法−
花かつお500gを蒸留水4Lに入れ、沸騰させて2時間加温抽出した。放冷後、濾過して濾液を集めた。濾別した花かつおに再び蒸留水4Lを加え沸騰させてさらに1時間加温抽出した。放冷後、同様に濾過して濾液を集め、先の濾液と合わせた後、240mLまで減圧濃縮した。得られた濃縮液にエタノールを添加し、生じた沈殿物を濾過によって集め、カツオ抽出物を得た(11.4g)。沈殿物の一部を水に溶かし、薄層クロマトグラフィー(展開液;n−ブタノール:氷酢酸:エタノール:蒸留水=4:1:1:2で展開し、ヒスチジンのスポットを確認した。)
サンプルIおよびサンプルIIを粉砕して粉末としたものを一定の割合で高脂肪高ショ糖食に添加した。サンプルI中のヒスチジン含量はアミノ酸自動測定器による測定結果0.6mg/gであった。ポタコーゲン(登録商標)はサンプルIの1g中に76.6mg含まれる。
-Preparation method of bonito extract-
500 g of flower bonito was placed in 4 L of distilled water, boiled, and extracted by heating for 2 hours. After cooling, the filtrate was collected by filtration. 4 L of distilled water was again added to the filtered flower bonito and boiled, followed by heating and extraction for another hour. After allowing to cool, the filtrate was collected in the same manner, and the filtrate was collected. The filtrate was combined with the previous filtrate, and then concentrated under reduced pressure to 240 mL. Ethanol was added to the obtained concentrated liquid, and the resulting precipitate was collected by filtration to obtain a skipjack extract (11.4 g). A part of the precipitate was dissolved in water and thin-layer chromatography (developing solution; developed with n-butanol: glacial acetic acid: ethanol: distilled water = 4: 1: 1: 2 to confirm histidine spots).
Samples I and II were pulverized and added to a high-fat high-sucrose diet at a constant rate. The histidine content in Sample I was 0.6 mg / g as a result of measurement using an amino acid automatic measuring instrument. Potacogen (registered trademark) is contained in 16.6 g of Sample I at 76.6 mg.

高脂肪高ショ糖食(牛脂、ラードなどの脂肪含量30%、オリエンタル酵母工業(株))、MF標準飼料(オリエンタル酵母工業(株))およびSD系メスラット(6週齢、日本チャールズ・リバー(株))をそれぞれ購入して準備した。   High fat high sucrose diet (beef tallow, lard fat content 30%, Oriental Yeast Industry Co., Ltd.), MF Standard Feed (Oriental Yeast Industry Co., Ltd.) and SD female rats (6 weeks old, Charles River Japan ( Co.)) was purchased and prepared.

2.実験方法
SD系メスラットを4群(各6匹)に分け、対照群にはラットMF標準飼料が10%となるように、高脂肪高ショ糖食餌に混合して自由摂取させた。また、検体であるサンプルIおよびサンプルIIのクッキーを粉砕後それぞれ高脂肪高ショ糖食餌に10%混合した餌を実験群群とし、普通群にはラットMF標準飼料をそれぞれ自由摂取させ、下記の項目(1〜4)を試験した。
(1)体重を実験開始日と実験開始後1週間おきに連続6週間測定した。
(2)実験最終日にラットを犠牲にして下腹部皮下脂肪、腹腔内白色脂肪を摘出し、これらの重量を測定した。
(3)各群の餌摂取量は実験開始前一週間から実験終了までに三日間おきにラット一匹当たりの平均摂取量を算出した。
(4)統計解析は、平均値の差の検定をDunnett,t−試験により行い、p<0.05、p<0.01をそれぞれ有意差あり*、**とした。
2. Experimental Method SD female rats were divided into 4 groups (6 rats each), and the control group was mixed with a high fat and high sucrose diet so that the rat MF standard diet was 10%, and was freely ingested. In addition, the sample cookie of sample I and sample II was ground and then mixed with 10% high fat and high sucrose diet as the experimental group, and the normal group was allowed to freely ingest the rat MF standard diet. Items (1-4) were tested.
(1) The body weight was measured for 6 consecutive weeks on the start date of the experiment and every other week after the start of the experiment.
(2) The rats were sacrificed on the last day of the experiment, and the lower abdominal subcutaneous fat and intraperitoneal white fat were removed and their weights were measured.
(3) The food intake of each group was calculated as the average intake per rat every three days from one week before the start of the experiment to the end of the experiment.
(4) Statistical analysis was performed by Dunnett, t-test for the difference between the mean values, and p <0.05 and p <0.01 were significant differences * and **, respectively.

3.結果
高脂肪高ショ糖食投与によるラット体脂肪蓄積に対する、ポタコーゲン(登録商標)とヒスチジンとを含有するクッキーの抗肥満作用を検討した。
3. Results The anti-obesity effect of cookies containing Potacogen (registered trademark) and histidine on rat body fat accumulation by administration of a high-fat and high-sucrose diet was examined.

高脂肪高ショ糖食投与群(対照群)のラットは、6週間の飼育により、MF標準飼料投与群(普通群)のラットと比較して、平均で約2.3倍の体重増加を示した。これに対し、サンプルIおよびサンプルII添加の実験群では、対照群のラットと比較して、それぞれ、平均で34.3%および27.8%の体重減少が認められた。また、腹部皮下脂肪含量の変化は、サンプルIおよびサンプルIIのクッキー添加実験群のラットでは、対照群のラットと比較して、それぞれ平均で39.2%と31.7%の減少が認められた。腹腔内白色脂肪の変化は、サンプルIおよびサンプルIIのクッキー添加実験群のラットでは、対照群のラットと比較して、それぞれ平均で54.9%と49.3%と著しい減少が認められた。   Rats in the high fat and high sucrose diet group (control group) showed an average weight gain of about 2.3 times that of rats in the MF standard feed group (normal group) after 6 weeks of breeding. It was. In contrast, in the experimental group to which Sample I and Sample II were added, an average of 34.3% and 27.8% weight loss was observed, respectively, compared with the control group of rats. In addition, the change in the abdominal subcutaneous fat content was found to decrease by 39.2% and 31.7% on average in the rats of the cookie addition experimental group of Sample I and Sample II, respectively, as compared with the rats of the control group. It was. The changes in intraperitoneal white fat were significantly decreased in the samples of the sample I and sample II cookie-added experimental groups, on average, 54.9% and 49.3%, respectively, as compared with the rats in the control group. .

このようにサンプルIおよびサンプルIIのクッキーを添加した高脂肪高ショ糖食摂取により、ラット下腹部皮下脂肪および腹腔内白色脂肪の増加を有意に減少させることが明らかとなった。   Thus, it has been clarified that the intake of the high fat and high sucrose diet to which the cookies of Sample I and Sample II are added significantly reduces the increase in rat lower abdominal subcutaneous fat and intraperitoneal white fat.

また、サンプルIIのクッキー添加実験群の結果から、ラット下腹部皮下脂肪量および腹腔内白色脂肪量が減少していることから、ポタコーゲン(登録商標)とおからの組み合わせによっても、体脂肪の増加を有意に減少させることが明らかとなった。ラットの餌の1日平均摂取量は、普通群で約16gであり、対照群と実験群の2群のいずれとも約14gであり、高脂肪高ショ糖食餌群では摂食抑制作用が認められた。   In addition, from the results of the cookie addition experiment group of Sample II, the amount of subcutaneous fat in the lower abdomen and the amount of white fat in the abdominal cavity of the rat decreased, so that combination of Potacogen (registered trademark) and okara also increased body fat. It became clear that it decreased significantly. The average daily intake of rat food is about 16 g in the normal group, and about 14 g in both the control group and the experimental group, and the high-fat and high-sucrose diet group has an antifeeding effect. It was.

(実施例4)
ポタコーゲン(登録商標):L−ヒスチジン:L−シトルリン=10:1:1.5の比率混合物を作り、混合粉末Aとした。混合粉末Aを62%、還元麦芽糖水飴粉末35.5%、ショ糖脂肪酸エステル1%、第三リン酸カルシウム1%を混合し、直径8mm、250mg/粒の打錠品を成形した。一粒の数値は平均重量249.7g/粒、錠剤硬度平均値12.5kg/cm、錠厚平均値4.9mmであった。
Example 4
Potacogen (registered trademark): L-histidine: L-citrulline = 10: 1: 1.5 ratio mixture was made and mixed powder A was obtained. 62% of mixed powder A, 35.5% of reduced maltose starch syrup powder, 1% of sucrose fatty acid ester and 1% of tribasic calcium phosphate were mixed to form a tableted product having a diameter of 8 mm and 250 mg / grain. The numerical value of one grain was an average weight of 249.7 g / grain, an average tablet hardness of 12.5 kg / cm 2 , and an average tablet thickness of 4.9 mm.

混合粉末Aの添加量は95%〜10%で打錠可能であり、錠剤の重量形状に合わせて含有量をコントロールできる。1錠中のポタコーゲン(登録商標)、L−ヒスチジンおよびL−シトルリンの計算上の含量は、それぞれ124mg、12.4mg、および18.6mgである。   Tableting is possible at an addition amount of the mixed powder A of 95% to 10%, and the content can be controlled according to the weight shape of the tablet. The calculated contents of Potacogen®, L-histidine and L-citrulline in one tablet are 124 mg, 12.4 mg and 18.6 mg, respectively.

(実施例5)
混合粉末Aを34%、還元麦芽糖水飴粉末25%、トレハロース10%、酸味料5%、高甘味料0.2%ミルクカルシウム3%、フルーツ香料1%、果汁粉末3%、デキストリン48.8%の重量割合で噴霧顆粒機を使用し、その際の噴霧液として水を使用して顆粒化した。本品は流動性のよい酸味と甘味のあるフルーツ系の顆粒が製造できた。混合粉末Aは1%〜90%の含量で増粘剤である糊剤溶液90〜10%を添加して噴霧顆粒化は可能である。
(Example 5)
34% of mixed powder A, reduced maltose starch syrup powder 25%, trehalose 10%, acidulant 5%, high sweetener 0.2% milk calcium 3%, fruit flavor 1%, fruit juice powder 3%, dextrin 48.8% The granulation was carried out using a spray granulator at a weight ratio of 5 and water as the spray liquid. This product was able to produce fruit-type granules with good fluidity and sourness and sweetness. The mixed powder A can be spray granulated by adding 90 to 10% of a paste solution as a thickener at a content of 1% to 90%.

(実施例6)
混合粉末A98%、第三リン酸カルシウム1%、ショ糖脂肪酸エステル1%の混合物をハードカプセル充填機にてカプセル錠を製造した。
(Example 6)
Capsule tablets were produced with a hard capsule filling machine of a mixture of mixed powder A 98%, tricalcium phosphate 1% and sucrose fatty acid ester 1%.

(実施例7)
混合粉末A37%、植物油55%、ミツロウ・グリセリン脂肪酸エステル8%の重量割合で混合しソフトカプセル充填製剤が得られた。
(Example 7)
A soft capsule-filled preparation was obtained by mixing 37% of mixed powder A, 55% vegetable oil, and 8% beeswax glycerin fatty acid ester.

(まとめ)
1.先ず、ポタコーゲン(登録商標)の脂肪の低減効果を実施例1によって検討した。その結果、4週間の飼育期間中に、25%フルクトース水溶液を自由摂取させた実験群において、ポタコーゲン(登録商標)0.2g/餌1gを含む飼料を与えた群のラットでは、ポタコーゲン(登録商標)を含まない飼料を与えた対照群と比較して、下腹部皮下脂肪が24.8%、腹腔内白色脂肪が19.3%減少していた。この結果よりポタコーゲン(登録商標)は体重増加作用のあるフルクトースの存在下においても体重減少作用および動物の組織の皮下脂肪含量を減少する作用を示すことが明らかとなった。
(Summary)
1. First, the fat reducing effect of Potacogen (registered trademark) was examined in Example 1. As a result, in the experimental group in which 25% fructose aqueous solution was ingested freely during the 4-week rearing period, in the group of rats fed with a diet containing 0.2 g of Potacogen (registered trademark) / 1 g of diet, Potacogen (registered trademark) ), The lower abdominal subcutaneous fat was reduced by 24.8% and the intraperitoneal white fat was reduced by 19.3%. From these results, it was clarified that Potacogen (registered trademark) exhibits an effect of reducing body weight and an effect of decreasing the subcutaneous fat content of animal tissues even in the presence of fructose having an effect of increasing body weight.

ポタコーゲン(登録商標)の脂肪を減少されるメカニズムは、ポタコーゲン(登録商標)の投与により、インスリンが上昇し、インスリン感受性ホルモンのレプチンに作用して、AMPキナーゼを活性化し、活性化されたAMPキナーゼが脂質代謝を調節し(Minokoshi、Yら:Leptin stimulates fatty acid oxidation by activating AMP−activated protein kinase、Nature、415:339−343、2002)、脂肪酸を燃焼させて脂肪分を減少したと推測される。   The mechanism of reducing the fat of Potacogen® is that the administration of Potacogen® increases insulin, acts on the insulin-sensitive hormone leptin, activates AMP kinase, and activates AMP kinase. Regulates lipid metabolism (Minokoshi, Y et al .: Leptin stimulated fatty acidification by activating AMP-activated protein kinase, Nature, 415: 339-343, 2002). .

2.ヒスチジンとポタコーゲン(登録商標)との組み合わせによって、ヒスチジンの使用量を非特許文献9に記載されるヒスタミンの摂食抑制作用発現濃度29mg/gより低い濃度で体脂肪減少効果を示すか否かを検討した(実施例2)。実施例2では、SD系メスラットを4群(各5匹)に分け、対照群には高脂肪高ショ糖食餌、試験対照群にはラットMF標準飼料を10%高脂肪高ショ糖食餌に混合し自由摂取させた。また、検体であるヒスチジンとポタコーゲン(登録商標)の配合末を高脂肪高ショ糖食餌に10%混合した餌をPoG群とし、普通群にはラットMF標準飼料をそれぞれ自由摂取させ、4群のラットを連続39日間飼育後犠牲にして体重、腹部皮下脂肪含量、腹部皮下脂肪含量を測定した。PoG群の餌1g中にはポタコーゲン(登録商標)50mg、L−ヒスチジン5mgが含まれる(実施例2)。ポタコーゲン(登録商標)50mgとL−ヒスチジン5mgでその比率は10:1となっているが、その比率に限定されるものではない。   2. Whether or not a combination of histidine and Potacogen (registered trademark) exhibits a body fat reduction effect when the amount of histidine used is lower than the 29 mg / g expression level of histamine feeding suppression described in Non-Patent Document 9. Examined (Example 2). In Example 2, SD female rats were divided into 4 groups (5 each), the control group was mixed with a high fat high sucrose diet, and the test control group was mixed with a 10% high fat high sucrose diet. And allowed to ingest freely. In addition, a diet in which 10% of the mixed powder of histidine and Potacogen (registered trademark) as a sample was mixed with a high-fat high-sucrose diet was used as the PoG group. Rats were raised for 39 consecutive days and sacrificed, and body weight, abdominal subcutaneous fat content, and abdominal subcutaneous fat content were measured. Potacogen (registered trademark) 50 mg and L-histidine 5 mg are contained in 1 g of feed of the PoG group (Example 2). Potacogen (registered trademark) 50 mg and L-histidine 5 mg have a ratio of 10: 1, but the ratio is not limited.

高脂肪高ショ糖食投与群(対照群)のラットはMF標準飼料投与群(普通群)のラットより39日間の飼育により2.5倍以上の体重増加を示した。そして10%MF標準飼料添加高脂肪高ショ糖食投与群(試験対照群)は、高脂肪高ショ糖食投与群(対照群)より体重が約11%減少にもかかわらず、10%PoG−His配合末添加の高脂肪高ショ糖食投与群(PoG群)では約26%の体重減少を認めた。その体重減少の中身として脂肪含量を調べた結果次のようであった。すなわち、PoG群の腹部皮下脂肪含量は試験対照群のそれよりより約34%減少した。また、PoG群の腹腔内白色脂肪含量は試験対照群のそれよりより約48%減少した。このようにPoG−His配合末添加の高脂肪高ショ糖食投与によりラット下腹部皮下脂肪および腹腔内白色脂肪の増加を有意に減少させることが明らかとなった。   Rats in the high fat high sucrose diet group (control group) showed a 2.5-fold increase in body weight after 39 days of breeding compared to rats in the MF standard feed group (normal group). The 10% MF standard feed-added high fat high sucrose diet administered group (test control group) was 10% PoG-, although the body weight decreased by about 11% compared to the high fat high sucrose diet administered group (control group). In the high fat high sucrose diet administration group (PoG group) to which the His compound was added, weight loss of about 26% was observed. As a result of examining the fat content as the contents of the weight loss, it was as follows. That is, the abdominal subcutaneous fat content of the PoG group was reduced by about 34% from that of the test control group. In addition, the intraperitoneal white fat content in the PoG group was reduced by about 48% from that in the test control group. Thus, it was revealed that administration of a high-fat and high-sucrose diet containing PoG-His compounded powder significantly reduced the increase in rat lower abdominal subcutaneous fat and intraperitoneal white fat.

この結果、餌1g中にポタコーゲン(登録商標)50mg、L−ヒスチジン5mgが含まれている。これは実施例1で示したポタコーゲン(登録商標)含有量0.2g/餌1gより低含量であり、また、非特許文献9記載のヒスタミンの摂食抑制作用発現濃度29mg/gより低含量で体脂肪減少効果を示している。このことより、ヒスチジンとポタコーゲン(登録商標)との組み合わせによって体脂肪減少に対して相乗効果を示すことが明らかになった。   As a result, 1 mg of bait contains 50 mg of Potacogen (registered trademark) and 5 mg of L-histidine. This is lower than the Potacogen (registered trademark) content 0.2 g / g 1 g shown in Example 1, and the histamine feeding inhibitory expression level described in Non-Patent Document 9 is lower than 29 mg / g. It shows body fat reduction effect. This revealed that the combination of histidine and Potacogen (registered trademark) has a synergistic effect on body fat reduction.

3.さらに、ヒスチジンとポタコーゲン(登録商標)の相乗効果を明らかにするために、ヒスチジンとポタコーゲン(登録商標)とを添加したクッキーによるラットに対する影響(6週間飼育)を調べて次のような結果を得た(実施例3)。   3. Furthermore, in order to clarify the synergistic effect of histidine and Potacogen (registered trademark), the effect of rats with histidine and Potacogen (registered trademark) on rats (bred for 6 weeks) was examined and the following results were obtained. (Example 3).

高脂肪高ショ糖食投与群(対照群)のラットはMF標準飼料投与群(普通群)のラットより6週間の飼育により約2.3倍の体重増加を示した。それに対して、餌1g中にヒスチジン含量0.6mg/gとポタコーゲン(登録商標)は76.6mg含量のクッキーでは対照群のそれの34.3%の体重減少がみとめられた。また、腹部皮下脂肪含量と腹腔内白色脂肪の変化は対照群のそれぞれ39.2%と54.9%と著しい減少が認められ、ヒスチジンとポタコーゲン(登録商標)との組み合わせによって体脂肪減少に対してヒスチジンとポタコーゲン(登録商標)の両者とも低含量で相乗効果を示すことが明らかになった。   The rats in the high fat and high sucrose diet group (control group) showed about 2.3-fold increase in body weight after breeding for 6 weeks compared with the rats in the MF standard diet group (normal group). In contrast, a histidine content of 0.6 mg / g per 1 g of feed and Potacogen (registered trademark) of 76.6 mg content showed a weight loss of 34.3% that of the control group. The changes in the abdominal subcutaneous fat content and intraperitoneal white fat were 39.2% and 54.9%, respectively, in the control group, showing a significant decrease. The combination of histidine and Potacogen (registered trademark) reduced body fat. It was revealed that both histidine and Potacogen (registered trademark) show a synergistic effect at a low content.

実施例3の餌には廃棄物利用の目的で食物繊維高含有量のおからを増量の目的で使用したが、ポタコーゲン(登録商標)とおからを共に餌1g中に76.6mg添加したクッキーによって、対照群のそれの27.8%の体重減少がみとめられた。また、腹部皮下脂肪含量と腹腔内白色脂肪の変化は対照群のそれぞれ31.7%と49.3%と著しい減少が認められた。これにより、ラットの体脂肪減少に対してポタコーゲン(登録商標)とおからの組み合わせも有効であることが明らかになった。おからの代わりに結晶セルロース、アラビアガムおよびアルギン酸などの水溶性植物繊維を含む食物繊維類を利用することも考えられる。   The bait of Example 3 was used for the purpose of increasing the amount of the high content of dietary fiber from the waste for the purpose of waste utilization, but by using a cookie in which 76.6 mg of Potacogen (registered trademark) and okara were added to 1 g of bait. A weight loss of 27.8% of that of the control group was observed. In addition, changes in the abdominal subcutaneous fat content and intraperitoneal white fat were significantly reduced to 31.7% and 49.3% in the control group, respectively. This revealed that the combination of Potacogen (registered trademark) and okara was also effective in reducing body fat in rats. It is also conceivable to use dietary fibers containing water-soluble plant fibers such as crystalline cellulose, gum arabic and alginic acid instead of okara.

抗肥満作用を有する組成物が提供される。この組成物は、飼料または食品のサプリメントとして添加されて、ヒトおよびペットを含む動物に応用して、肥満解消に役立てることができる。   Compositions having anti-obesity activity are provided. This composition can be added as a feed or food supplement and applied to animals including humans and pets to help eliminate obesity.

Claims (5)

動物の肥満を防ぐための組成物であって、低分子多糖類を含み、該組成物は、該動物が摂取する食品または飼料と該低分子多糖類との重量比が1:130〜20:80の割合になるように該食品または飼料とともに摂取され、該低分子多糖類が約16個のD−グルコースからなり、かつ約6個のD−グルコースのホモグルコース鎖を単位とする螺旋構造をもつ、組成物。 A composition for preventing obesity of an animal, comprising a low molecular weight polysaccharide, wherein the composition has a weight ratio of food or feed consumed by the animal and the low molecular weight polysaccharide of 1: 130 to 20: Ingested with the food or feed in a ratio of 80, the low-molecular-weight polysaccharide is composed of about 16 D-glucose, and has a helical structure with about 6 D-glucose homoglucose chains as a unit. Having a composition. さらにヒスチジン、カツオ抽出物または食物繊維を含む、請求項1に記載の組成物。 The composition of claim 1 further comprising histidine, bonito extract or dietary fiber. 前記ヒスチジンと前記低分子多糖類とを、約1:10〜約1:127の割合の重量比で含む、請求項2に記載の組成物。 3. The composition of claim 2, comprising the histidine and the low molecular weight polysaccharide in a weight ratio of about 1:10 to about 1: 127. 前記低分子多糖類と前記食物繊維とを、約1:1の重量比で含む、請求項2に記載の組成物。 The composition of claim 2, comprising the low molecular weight polysaccharide and the dietary fiber in a weight ratio of about 1: 1. 錠剤、顆粒カプセル製剤およびクッキーからなる群から選択される形態である、請求項1〜4のいずれか1項に記載の組成物。 The composition of any one of Claims 1-4 which is a form selected from the group which consists of a tablet, a granular capsule formulation, and a cookie.
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