JP2005281188A - Regulant of in vivo lipid - Google Patents
Regulant of in vivo lipid Download PDFInfo
- Publication number
- JP2005281188A JP2005281188A JP2004097373A JP2004097373A JP2005281188A JP 2005281188 A JP2005281188 A JP 2005281188A JP 2004097373 A JP2004097373 A JP 2004097373A JP 2004097373 A JP2004097373 A JP 2004097373A JP 2005281188 A JP2005281188 A JP 2005281188A
- Authority
- JP
- Japan
- Prior art keywords
- lipid
- vivo
- vivo lipid
- cordierigosaccharide
- lipid regulator
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
Description
本発明は、新規な生体内脂質調節剤に関し、より詳細には、コージオリゴ糖を有効成分として含有する生体内脂質調節剤、及びこれを配合してなる組成物に関するものである。 TECHNICAL FIELD The present invention relates to a novel in vivo lipid regulator, and more particularly to an in vivo lipid regulator containing cordierigosaccharide as an active ingredient, and a composition comprising the same.
近年、我が国を含め多くの国において、生活水準の向上にともない、食習慣が欧米化し、従来に比して、カロリーや脂肪が過剰に摂取されるにようになり、高脂血症、高コレステロール血症、糖尿病、高血圧症、肥満などの生活習慣病の患者やその予備群が増加してきている。なかでも、生体内の脂質の過剰な増加に起因する肥満は、これら生活習慣病の危険因子として健康上大きな問題となっている。さらに、肥満は、高脂血症、高コレステロール血症、循環器系疾患、肝臓疾患、悪性新生物発生の危険因子であり、また、痛風、胆石症などの発症や悪化にも強く関係しているといわれている。 In recent years, in many countries including Japan, dietary habits have become westernized as the standard of living has improved, resulting in excessive intake of calories and fat compared to the past, resulting in hyperlipidemia and high cholesterol. Patients with lifestyle-related diseases such as blood glucose, diabetes, hypertension and obesity and their reserve groups are increasing. Among them, obesity caused by excessive increase of lipids in the living body is a serious health problem as a risk factor of these lifestyle-related diseases. In addition, obesity is a risk factor for the development of hyperlipidemia, hypercholesterolemia, cardiovascular disease, liver disease, and malignant neoplasms, and is also strongly associated with the onset and exacerbation of gout and cholelithiasis. It is said that there is.
特に、高齢化社会を目前にした日本では、予防医学の観点から、生活習慣病の危険因子である肥満の予防は、重要な課題として取り上げられている。また、特に思春期以降の女性の肥満回避への意識は非常に強く、そのため、誤った方法や身体に過度の負担となるダイエットが原因で、ホルモンバランスの変調や、骨粗鬆症などの重篤な症状に陥るなどの問題が生じている。 Particularly in Japan, where an aging society is imminent, prevention of obesity, which is a risk factor for lifestyle-related diseases, has been taken up as an important issue from the viewpoint of preventive medicine. In particular, women after puberty are very conscious of avoiding obesity, and as a result, hormonal balance modulation and severe symptoms such as osteoporosis are caused by wrong methods and diets that place an excessive burden on the body. Problems such as falling into.
一般に、肥満や高脂血症の治療や予防の手段としては、低脂肪や低カロリーの食品を摂取してカロリーを制限する方法や、有酸素運動により消費カロリーを増加する方法が推奨されている。しかし、食事制限による摂取カロリーの制限や、運動により消費カロリーを増加させるためには、適切な指導が必要であり、その期間も長期に及ぶため、実際には、途中で断念する場合も多い。また、食事を制限することは、精神衛生上も好ましくない。薬物の服用は効果的ではあるものの、副作用やコストに問題がある。 In general, as a means of treatment and prevention of obesity and hyperlipidemia, a method of limiting calories by ingesting low-fat or low-calorie foods or a method of increasing calorie consumption by aerobic exercise is recommended. . However, in order to limit calorie intake due to dietary restrictions and to increase calorie consumption due to exercise, appropriate guidance is necessary and the period is long, so in fact, it is often abandoned on the way. Moreover, restricting meals is not preferable for mental health. Although taking drugs is effective, there are problems with side effects and costs.
日常の食生活において、美味しくて、安全な食事、間食、或いは健康食品を摂取しながら、同時に、肥満、高脂血症、高コレステロール血症などの予防が効果的に実践できることは、これらの疾患を持つ患者やその予備群にとっては、特に望ましいことである。そこで、食品業界では、それ単独で摂取しても、或いは、食事として摂取しても美味で、且つ、肥満、高脂血症、高コレステロール血症などの予防や治療に有効な作用効果を有する素材の開発が進められている。さらに、近年の健康ブーム、或いは、特定保健用食品などの保健機能食品制度の創設に伴い、飲食品による肥満、高脂血症、高コレステロール血症などの予防や治療に関する一般の認識も高まっていることを反映して、既に、脂質やコレステロールの体内への吸収を阻害するジアシルグリセロールや植物ステロールのような脂肪や、高甘味度甘味料や糖アルコールなどの低カロリー甘味料が食品素材として多数市販されている。また、例えば、特許文献１乃至３には、キシログルカンやアガロオリゴ糖などの糖質を有効成分とする脂肪の低減剤が、特許文献４にはヘスペレチンやナリンゲニンなどを有効成分とする脂質代謝改善剤が記載されている。さらに、非特許文献１には、セルロースやガム類などをはじめとする食物繊維が、脂質代謝、胆汁酸代謝、コレステロール代謝などに関与していることが記載されており、これらは生活習慣病の改善効果があることが記載されている。しかしながら、これらの中には、飲食品の原料として使用した場合には、その飲食品の味、香り、食感等の風味の低下をきたすものや、大量に摂取しないと効果が認められないものや、体調や体質によっては、下痢などが発生するなどの問題のある食品素材も少なくない。現在の多様な食生活に対応するためには、継続的に摂取しても、摂取時の飲食品の味、香り、食感等の風味の低下をもたらすことなく、しかも、安全で、かつ、肥満、高脂血症、高コレステロール血症などの予防や治療効果を有する機能に優れた食品素材のさらなる開発が望まれている。 It is these diseases that prevention of obesity, hyperlipidemia, hypercholesterolemia, etc. can be effectively practiced at the same time while taking delicious and safe meals, snacks or health foods in daily eating habits. This is especially desirable for patients who have a disorder and their reserves. Therefore, in the food industry, even if it is taken alone or as a meal, it is delicious and has an effective effect for the prevention and treatment of obesity, hyperlipidemia, hypercholesterolemia, etc. Material development is underway. In addition, with the recent health boom or the establishment of health functional food systems such as foods for specified health use, public awareness about the prevention and treatment of obesity, hyperlipidemia, hypercholesterolemia, etc. due to food and drink has increased. Reflecting the fact that there are already many food ingredients such as fats such as diacylglycerol and plant sterols that inhibit the absorption of lipids and cholesterol into the body, and low-calorie sweeteners such as high-intensity sweeteners and sugar alcohols. It is commercially available. Further, for example, Patent Documents 1 to 3 describe fat reducing agents containing saccharides such as xyloglucan and agarooligosaccharide as active ingredients, and Patent Document 4 discloses a lipid metabolism improving agent containing hesperetin, naringenin and the like as active ingredients. Is described. Furthermore, Non-Patent Document 1 describes that dietary fibers such as cellulose and gums are involved in lipid metabolism, bile acid metabolism, cholesterol metabolism, etc., and these are related to lifestyle-related diseases. It is described that there is an improvement effect. However, among these, when used as a raw material for foods and drinks, those that cause a decrease in the flavor, aroma, texture, etc. of the food or drink, or those that are not effective unless consumed in large quantities In addition, depending on the physical condition and constitution, there are many food materials with problems such as diarrhea. In order to respond to the current diverse diet, even if it is continuously consumed, it does not cause a decrease in the flavor, aroma, texture, etc. of the food and drink at the time of consumption, and it is safe, There is a demand for further development of food materials with excellent functions for preventing and treating obesity, hyperlipidemia, hypercholesterolemia and the like.
一方、本出願人は、特許文献５及び非特許文献２乃至３において、コージオリゴ糖を含有する糖質の新規製造方法とこれらの糖質を含有する組成物を開示し、さらに、非特許文献３では、これらの糖質が、消化管内酵素による分解を受けにくく、食物繊維作用を有していることを開示した。しかしながら、これら本出願人自身による開示を含め特許文献１乃至５及び非特許文献１乃至３にはコージオリゴ糖、或いは、この糖質を含有する組成物に脂質の調節作用があることについては開示されていない。 On the other hand, the present applicants disclosed in Patent Document 5 and Non-Patent Documents 2 to 3 a novel method for producing saccharides containing cordierigosaccharides and compositions containing these saccharides. 3 discloses that these carbohydrates are less susceptible to degradation by enzymes in the digestive tract and have a dietary fiber action. However, Patent Documents 1 to 5 and Non-Patent Documents 1 to 3, including the disclosure by the applicants themselves, disclose that cordierigosaccharides or compositions containing these carbohydrates have a lipid regulating action. It has not been.
本発明は、飲食品などから摂取した脂質や、生体内で合成された脂質が、血中に増加し、生体の組織や器官に蓄積することに起因して、肥満、高脂血症、高コレステロール血症などが進行し、循環器系疾患や糖尿病など生活習慣病が重篤な状態へと進行することを予防、或いは、治療するための生体内脂質調節剤を提供することを第一の課題とし、また、この生体内脂質調節剤を配合してなる脂質調節用の組成物を提供することを第二の課題とするものである。 The present invention relates to obesity, hyperlipidemia, hyperlipidemia caused by the fact that lipids ingested from foods and drinks and lipids synthesized in vivo increase in blood and accumulate in tissues and organs of the body. The first is to provide an in vivo lipid regulator for preventing or treating the progression of cholesterolemia and the like, and the progression of life-style related diseases such as cardiovascular diseases and diabetes to serious conditions. It is a second object to provide a composition for lipid regulation obtained by blending this in vivo lipid regulator.
本発明者らは、上記の課題を解決する目的で、糖質を有効成分とする生体内脂質調節剤について長年に渡り研究を進めてきた。その結果、コージオリゴ糖が、生体内の脂質調節に強く働くこと、さらには、体重の増加の抑制や、血中コレステロールを健常値、或いは、より健常値に近い範囲に調節する作用を有することを見出し、新規な生体内脂質調節剤、及び、この生体内脂質調節剤を配合してなる脂質調節用の組成物を確立し、本発明を完成するに至った。 For the purpose of solving the above-mentioned problems, the present inventors have made researches for many years on in vivo lipid regulators containing carbohydrate as an active ingredient. As a result, Koji oligosaccharide has a strong effect on lipid regulation in vivo, and further has an effect of suppressing body weight gain and regulating blood cholesterol to a healthy value or a range closer to a healthy value. Have been found, and a novel lipid regulating agent in vivo and a composition for lipid regulation formed by blending this in vivo lipid regulating agent have been established, and the present invention has been completed.
本発明の生体内脂質調節剤は、摂取することにより、ヒトを含む動物の体内の脂質の量を健常値、或いは、より健常値に近い範囲に調節することができ、高脂血症などをはじめとする生体内脂質量の異常に起因する生活習慣病の改善が期待できる。 The in vivo lipid regulator of the present invention, when ingested, can adjust the amount of lipid in the body of animals including humans to a healthy value or a range closer to a healthy value, such as hyperlipidemia. Improvement of lifestyle-related diseases caused by abnormal lipid levels in the body can be expected.
本発明の生体内脂質調節剤の有効成分であるコージオリゴ糖とは、分子内にα−１，２−グルコシド結合を一箇所以上含むオリゴ糖を意味し、α−１，２−グルコシド結合のみを有するオリゴ糖の他、α−１，２−グルコシド結合とそれ以外の結合とを有するオリゴ糖も含む。具体的には、二糖であるコージビオース［Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−Ｄ−グルコピラノース］、三糖であるコージトリオース［Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−Ｄ−グルコピラノース］、セラギノース（コージビオシルグルコシド）［Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１，１）−α−Ｄ−グルコピラノシド］、又はコージビオシルフラクトシド［Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１，２）−β−Ｄ−フラクトフラノシド］、四糖であるコージテトラオース［Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−Ｄ−グルコピラノース］、コージトリオシルグルコシド［Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１→２）−Ｏ−α−Ｄ−グルコピラノシル−（１，１）−α−Ｄ−グルコピラノシド］などが例示できる。 Koji oligosaccharide which is an active ingredient of the in vivo lipid regulator of the present invention means an oligosaccharide having one or more α-1,2-glucoside bonds in the molecule, and only α-1,2-glucoside bonds. In addition to oligosaccharides having the above, oligosaccharides having an α-1,2-glucoside bond and other bonds are also included. Specifically, Codybiose [O-α-D-glucopyranosyl- (1 → 2) -OD-glucopyranose], which is a disaccharide, and Kojitriose [O-α-D-glucopyranosyl- (, which is a trisaccharide, 1 → 2) -O-α-D-glucopyranosyl- (1 → 2) -O-D-glucopyranose], ceraginose (codybiosylglucoside) [O-α-D-glucopyranosyl- (1 → 2) -O -Α-D-glucopyranosyl- (1,1) -α-D-glucopyranoside], or Kojibiosyl fructoside [O-α-D-glucopyranosyl- (1 → 2) -O-α-D-glucopyranosyl- ( 1,2) -β-D-fructofuranoside], a tetrasaccharide, Codytetraose [O-α-D-glucopyranosyl- (1 → 2) -O-α-D-glucopyranosyl- (1 → 2)- O-α-D- Lucopyranosyl- (1 → 2) -OD-glucopyranose], corditriosyl glucoside [O-α-D-glucopyranosyl- (1 → 2) -O-α-D-glucopyranosyl- (1 → 2) -O -Α-D-glucopyranosyl- (1,1) -α-D-glucopyranoside] and the like.
本発明で使用されるコージオリゴ糖は、上記の構造を有するものである限り、その由来や製法は特に限定されず、発酵法、酵素法、有機合成法など、いずれの方法により製造されたものでもよい。これらの方法により得られる反応液は、コージオリゴ糖、或いは、これを含有する糖質を含む溶液として、そのまま、或いは、イオン交換樹脂などで、部分精製して、さらには、高純度に精製して用いることができる。コージオリゴ糖は、例えば、特許文献５に開示した、糖供与体β−グルコース １−リン酸と、糖受容体グルコ−スまたはスクロース、ガラクトース、キシロースなどをコージビオースホスホリラーゼによって変換する方法、或いは、トレハロースホスホリラーゼとコージビオースホスホリラーゼを組み合わせてトレハロースから、または、マルトースホスホリラーゼとコージビオースホスホリラーゼを組み合わせてマルトースからコージオリゴ糖を製造する方法、また、特開２００３−１６９６６５号公報に開示されている、パエシロマイセス（Ｐａｅｃｉｌｏｍｙｃｅｓ ｓｐ．）属真菌に由来するα−グルコシダーゼをα−グルコオリゴ糖に作用させて製造する方法などの、酵素法により製造することができる。このうち、コージビオースホスホリラーゼと、それ以外の二糖ホスホリラーゼとのカップリングによる製造方法は、マルトースやトレハロースなどの豊富で安価な糖質を原料とし、高効率かつ安価にコージオリゴ糖を製造できることから、工業的に有利に実施できる。 As long as the cord oligosaccharide used in the present invention has the above-mentioned structure, its origin and production method are not particularly limited, and those produced by any method such as fermentation method, enzyme method, organic synthesis method, etc. But you can. The reaction solution obtained by these methods is prepared as a solution containing cordierigosaccharide or a saccharide containing this, as it is, or partially purified with an ion exchange resin or the like, and further purified to a high purity. Can be used. The cord oligosaccharide is, for example, a method disclosed in Patent Document 5, in which a sugar donor β-glucose 1-phosphate and a sugar acceptor glucose or sucrose, galactose, xylose, etc. are converted by cordobiose phosphorylase, or , A method of producing cordierigosaccharide from trehalose by combining trehalose phosphorylase and cordobiose phosphorylase or from maltose by combining maltose phosphorylase and cordobiose phosphorylase, and disclosed in JP-A No. 2003-169665 And α-glucosidase derived from a fungus belonging to the genus Paecilomyces sp. Among these, the production method by the coupling of cordobiose phosphorylase and other disaccharide phosphorylases is capable of producing co-oligosaccharides with high efficiency and low cost from abundant and inexpensive carbohydrates such as maltose and trehalose. Therefore, it can be industrially advantageous.
本発明の生体内脂質調節剤により調節する脂質とは、生体内に存在する、単純脂質、複合脂質、及び、誘導脂質を意味し、具体的には、トリグリセリドなどの中性脂肪などの単純脂質、グリセロリン脂質、グリセロ糖脂質、スフィンゴリン脂質、スフィンゴ糖脂質などの複合脂質、高密度リポ蛋白コレステロール（ＨＤＬ−コレステロール）、低密度リポ蛋白コレステロール（ＬＤＬ−コレステロール）、レムナント様リポ蛋白コレステロールなど血漿リポ蛋白や細胞膜中のリポ蛋白など複合脂質、及び、ステアリン酸、パルミチン酸などの飽和脂肪酸、α−リノール酸、α−リノレン酸などの不飽和脂肪酸、多価不飽和脂肪酸などを含む遊離脂肪酸、脂肪族アルコール、ステロイド、コレステロールなどの誘導脂質をいう。なお、本明細書中では、血液中の高密度リポ蛋白コレステロール（ＨＤＬ−コレステロール）、低密度リポ蛋白コレステロール（ＬＤＬ−コレステロール）、レムナント様リポ蛋白コレステロールなど血漿リポ蛋白に含まれるコレステロール及び遊離コレステロールを併せて総コレステロールと呼ぶ場合がある。 The lipid that is regulated by the in vivo lipid regulator of the present invention means a simple lipid, a complex lipid, and a derived lipid that exist in the living body. Specifically, a simple lipid such as a neutral fat such as triglyceride. , Glycerophospholipid, glyceroglycolipid, sphingophospholipid, glycosphingolipid and other complex lipids, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol), remnant-like lipoprotein cholesterol and other plasma lipo Free fatty acids and fats, including complex lipids such as proteins and lipoproteins in cell membranes, saturated fatty acids such as stearic acid and palmitic acid, unsaturated fatty acids such as α-linoleic acid and α-linolenic acid, polyunsaturated fatty acids, etc. Derived lipids such as family alcohols, steroids and cholesterol. In the present specification, cholesterol and free cholesterol contained in plasma lipoproteins such as high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), and remnant-like lipoprotein cholesterol in blood are used. Sometimes referred to as total cholesterol.
本発明の生体内脂質調節剤は、生体内の脂質を健常或いはそれに近い状態に低減及び／又は維持する効果を発揮出来ればよく、コージオリゴ糖のみで構成されていてもよいし、コージオリゴ糖の製造方法に由来するグルコース、イソマルトース、マルトース、オリゴ糖、デキストリンなどの他の糖質を含有していてもよい。本発明の生体内脂質調節剤が、さらにアミノ酸などの分子内にアミノ基を含む生理活性物質などを含む場合には、グルコースをはじめとする還元性糖質が混在するとメイラード反応などによりアミノ基を含む生理活性物質が変化し、生体内脂質調節剤の品質低下が予想される。このような場合には本発明の生体内脂質調節剤は、メイラード反応をおこしにくいコージオリゴ糖の含量が比較的高いものが好適であり、或いは、コージオリゴ糖と共存する還元性の糖質を水素添加して、その還元性を低減したものを用いることも好ましい。また、コージオリゴ糖は安定な糖質なので、本発明の生体内脂質調節剤の効果や品質を低下させない範囲で、分散性の向上や増量などを含めたそれぞれの目的に応じて、還元性糖質、コージオリゴ糖を除く非還元性糖質、サイクロデキストリン、糖アルコール、水溶性多糖などの糖質、上記以外のフラボノイドやカテキンなどのポリフェノール、甘味料、香辛料、酸味料、旨味料、酒、有機酸、有機酸の塩、無機塩、乳化剤、香料、色素、酸化防止剤、キレート作用を有する物質から選ばれる１種又は２種以上と併用することも随意である。さらに必要であれば、公知の保存料、旨味料、甘味料、安定剤、アルコール、殺菌剤などの１種又は２種以上を適量併用することも随意である。このようにして得られた生体内脂質調節剤は、その形状を問わず、例えば、シラップ、ペースト、マスキット、粉末、結晶などの何れの形状であってもよい。 The in vivo lipid regulator of the present invention is only required to exhibit the effect of reducing and / or maintaining in vivo lipids in a healthy or near state, and may be composed only of cordierigosaccharides, or cordieroligosaccharides. It may contain other carbohydrates such as glucose, isomaltose, maltose, oligosaccharide, dextrin derived from the production method. When the in vivo lipid regulator of the present invention further contains a physiologically active substance containing an amino group in a molecule such as an amino acid, the amino group is reduced by a Maillard reaction or the like when reducing carbohydrates such as glucose are mixed. The physiologically active substance to be contained is changed, and the quality of the in vivo lipid regulator is expected to be lowered. In such a case, the in vivo lipid regulator of the present invention is preferably one having a relatively high content of cordierigosaccharide that does not easily undergo Maillard reaction, or a reducing carbohydrate that coexists with cordieroligosaccharide. It is also preferable to use a hydrogenated product having reduced reducing properties. In addition, since cordierigosaccharide is a stable saccharide, a reducing sugar can be used according to each purpose including improvement of dispersibility and increase in the amount within the range in which the effect and quality of the in vivo lipid regulator of the present invention are not deteriorated. Quality, non-reducing saccharides other than cordierigosaccharides, cyclodextrins, sugar alcohols, sugars such as water-soluble polysaccharides, polyphenols such as flavonoids and catechins other than the above, sweeteners, spices, acidulants, flavourants, sake, It is also optional to use in combination with one or more selected from organic acids, organic acid salts, inorganic salts, emulsifiers, fragrances, dyes, antioxidants, and substances having a chelating action. Further, if necessary, it is optional to use one or two or more kinds of known preservatives, flavourants, sweeteners, stabilizers, alcohols, bactericides and the like in appropriate amounts. The in vivo lipid regulator thus obtained may be in any shape such as syrup, paste, mass kit, powder, crystal, etc., regardless of its shape.
本発明の生体内脂質調節剤は、その味質を調整する目的で、必要に応じて、例えば、粉飴、ブドウ糖、マルトース、トレハロース、蔗糖、異性化糖、蜂蜜、メープルシュガー、イソマルトオリゴ糖、ガラクトオリゴ糖、フラクトオリゴ糖、ニゲロオリゴ糖、キシロオリゴ糖、アガロオリゴ糖、キトオリゴ糖、ビートオリゴ糖、特開平７−１４３８７６号公報などに開示されたα−グルコシルα，α−トレハロースやα−マルトシルα，α−トレハロースなどのα，α−トレハロースの糖質誘導体、ラクトスクロース、ソルビトール、マルチトール、ラクチトール、キシリトール、エリスリトール、ジヒドロカルコン、ステビオシド、α−グリコシルステビオシド、レバウディオシド、グリチルリチン、Ｌ−アスパルチル−Ｌ−フェニルアラニンメチルエステル、サッカリン、グリシン、アラニン、アセスルファムＫ、スクラロースなどのような糖質、甘味料などの１種または２種以上の適量と混合して使用することもできる。 The in vivo lipid regulator of the present invention is, for the purpose of adjusting its taste quality, for example, powder koji, glucose, maltose, trehalose, sucrose, isomerized sugar, honey, maple sugar, isomaltoligosaccharide, Galactooligosaccharides, fructooligosaccharides, nigerooligosaccharides, xylooligosaccharides, agarooligosaccharides, chitooligosaccharides, beet oligosaccharides, α-glucosyl α, α-trehalose and α-maltosyl α, α- Carbohydrate derivatives of α, α-trehalose such as trehalose, lactosucrose, sorbitol, maltitol, lactitol, xylitol, erythritol, dihydrochalcone, stevioside, α-glycosyl stevioside, rebaudioside, glycyrrhizin, L-aspartyl-L-phenylalanine Possible ester, saccharin, glycine, alanine, acesulfame K, carbohydrates such as sucralose, also be used in admixture with one or more appropriate amount, such as sweeteners.
本発明の生体内脂質調節剤は、その有効成分であるコージオリゴ糖を、合計で、無水物換算で、約５質量％（以下、本明細書では「質量％」を単に「％」と略称する。）以上、望ましくは、１０％以上、さらに望ましくは２０％以上含有するものが好適である。 The in vivo lipid regulating agent of the present invention is a total of about 5% by mass of the cordierigosaccharide as an active ingredient in terms of anhydride (hereinafter, “mass%” is simply abbreviated as “%” in the present specification). More preferably, it contains 10% or more, more preferably 20% or more.
本発明でいう生体内脂質調節とは、生体内の脂質が代謝異常や飲食品の過剰摂取などにより血液などの体液中に増加するのを抑制したり、さらには、皮下、皮内、睾丸、腎臓、心臓、肝臓、消化管やその他の臓器、組織、或いは、これらの臓器や組織の周囲に存在する脂肪細胞、腱の周囲などに過剰に蓄積されて、脂肪肝や内臓脂肪などのように組織の脂質が増加、蓄積するのを抑制することによって、これらの部位における脂質を、健常或いはそれに近い状態に低減及び／又は維持することをいう。また、動脈硬化などにおいて血管壁に付着する、コレステロールや中性脂肪などの脂質を低減することも、当然、これに含まれる。 In vivo lipid regulation as used in the present invention is to suppress the increase of lipids in the body due to abnormal metabolism or excessive intake of food and drink, etc., and further, subcutaneous, intradermal, testicular, Overly accumulated in kidneys, heart, liver, gastrointestinal tract and other organs, tissues, fat cells existing around these organs and tissues, and around tendons, like fatty liver and visceral fat By suppressing the increase and accumulation of tissue lipids, it means reducing and / or maintaining the lipids at these sites to be healthy or close to them. Naturally, this also includes reducing lipids such as cholesterol and neutral fat that adhere to the blood vessel wall during arteriosclerosis.
本発明でいう生活習慣病とは、脂質の過度の蓄積により引き起こされる慢性の疾患をいい、具体的には、高脂血症、動脈硬化、高血圧、狭心症、心筋梗塞、脂肪肝、肝硬変、肥満、便秘、肝臓癌や大腸癌などの悪性新生物、糖尿病などを意味する。 The lifestyle-related diseases referred to in the present invention refers to chronic diseases caused by excessive accumulation of lipids, and specifically include hyperlipidemia, arteriosclerosis, hypertension, angina, myocardial infarction, fatty liver, cirrhosis. , Obesity, constipation, malignant neoplasms such as liver cancer and colon cancer, diabetes and the like.
本発明の生体内脂質調節剤は、ヒトのみでなく、ウシ、豚などの家畜、鶏、アヒルなどの家禽、タイ、ヒラメ、ハマチ、アサリ、ハマグリなどの養殖魚介類、エビ、カニなど養殖甲殻類、蚕、ミツバチなどの昆虫、犬、猫、鳥などのペットの動物なども使用の対象となる。また、本発明の生体内脂質調節剤は、これらのヒトを含む動物における脂質の増加の原因が、食事や餌の過剰摂取や、先天的、或いは、後天的な、脂質代謝異常などに起因する場合にも体内の脂質の増加の調節に使用することができる。さらに、本発明の生体内脂質調節剤は、生体内の脂質の増加が続き、肥満、高脂血症、高コレステロール血症などの生活習慣病と呼ばれる状態にあるもののみでなく、これらの状態を示す指標となる数値が、健常の範囲であっても、その範囲内で、脂質を低減させる目的で使用することも随意である。 The in vivo lipid regulator of the present invention is not limited to humans, but domestic animals such as cattle and pigs, poultry such as chickens and ducks, cultured seafood such as Thailand, flounder, hammertails, clams and clams, and cultured shells such as shrimps and crabs. Insects such as mosquitoes, moths and bees, pet animals such as dogs, cats and birds are also subject to use. Further, in the in vivo lipid regulator of the present invention, the cause of the increase in lipid in animals including these humans is due to excessive intake of food and food, congenital or acquired abnormal lipid metabolism, etc. In some cases it can also be used to regulate the increase in lipids in the body. Furthermore, the in vivo lipid regulator of the present invention continues to increase in vivo lipids, and is not only in the state called lifestyle-related diseases such as obesity, hyperlipidemia, hypercholesterolemia, but also in these states Even when the numerical value indicating the index is within a healthy range, it is optional to use it for the purpose of reducing lipid within the range.
本発明でいう肥満とは、ヒトの場合には、日本肥満学会の判定基準でいう、体重（ｋｇ）を身長（ｍ）で２回除したボディマスインデックス（ＢＭＩ）が、健常値上限の２５を超えている状態を意味する。また、ＢＭＩが２５以下であっても、組織や内臓の特定部位の脂質量が健常よりも多い場合を含むものであり、特に、生活習慣病の危険因子として挙げられる内臓脂質量が増加している場合を含むことはいうまでもない。 The obesity referred to in the present invention is, in the case of human beings, the body mass index (BMI) obtained by dividing the body weight (kg) by the height (m) twice according to the criteria of the Japanese Society of Obesity, and the healthy value upper limit of 25. It means a state that has been exceeded. In addition, even when the BMI is 25 or less, it includes cases where the amount of lipid in a specific part of tissue or viscera is higher than normal, and in particular, the amount of visceral lipid mentioned as a risk factor for lifestyle-related diseases increases. Needless to say, it includes cases where
本発明でいう高脂血症とは、血液及び／又は体液中の中性脂肪及び／又はコレステロールの含量が、健常値を超えている状態をいう。ヒトの場合には、血液中の中性脂肪の含量が、１００ｍｌ当たり１５０ｍｇを超える状態、及び／又は、高コレステロール血症にある場合をいう。本発明でいう高コレステロール血症とは、血液中の総コレステロールの含量が、１００ｍｌ当たり２２０ｍｇ以上の場合をいい、その値が１００ｍｌ当たり２２０ｍｇ以下の場合であっても、血液中の高密度リポ蛋白コレステロール（ＨＤＬ）の含量が１００ｍｌ当たり４１ｍｇ以下の場合や、血液中のレムナント様コレステロールの含量が１００ｍｌ当たり７．５ｍｇ以上の場合も含む。 The hyperlipidemia referred to in the present invention refers to a state in which the content of neutral fat and / or cholesterol in blood and / or body fluid exceeds a healthy value. In the case of humans, this refers to the case where the neutral fat content in the blood exceeds 150 mg per 100 ml and / or hypercholesterolemia. As used herein, hypercholesterolemia refers to a case where the total cholesterol content in blood is 220 mg or more per 100 ml, and even if the value is 220 mg or less per 100 ml, high-density lipoprotein in blood. This includes the case where the content of cholesterol (HDL) is 41 mg or less per 100 ml, and the case where the content of remnant-like cholesterol in blood is 7.5 mg or more per 100 ml.
本発明の生体内脂質調節剤の有効成分であるコージオリゴ糖は、安定で、しかも、飲食品の風味に殆ど影響を与えないことから、そのままで、あるいは、例えば、特許文献１乃至４に開示されているキシログルカンやその加水分解物、ポルフィランの加水分解物のガラクト硫酸オリゴ糖などの糖質や、ヘスペレチン、ナリンゲニンなどの、生体内の脂質代謝に影響を与えることの知られている１種又は２種以上の成分と適宜組み合わせて使用してもよく、さらには、非特許文献１に開示されたセルロース、ペクチン、プルランをはじめとする食物繊維と組み合わせることも自由である。また、これらの成分に加えて、ヘスペリジン、酵素処理ヘスペリジン、ナリンジン、酵素処理ナリンジン、ルチン、酵素処理ルチン、プロアントシアニジンなどのフラボノイド、カテキン、エピカテキン、エピガロカテキンなどのカテキン、さらには、ジアシルグリセロール、ポリエンホスファチジルコリンをはじめとする植物ステロール、ローヤルゼリー、プラバスタチンナトリウム、シンバスタチン、シンフィブラート、ニコチン酸、ニコモール、クリノフィブラート、クロフィブラート、パンテチン、酪酸リボフラビンなどの脂質の代謝調節に関与することが知られている公知の成分の１種又は２種以上を併用して、生体内脂質調節効果をさらに増強することも自由である。 Koji oligosaccharide, which is an active ingredient of the in vivo lipid regulator of the present invention, is stable and hardly affects the flavor of foods and drinks. Therefore, it is disclosed as it is or disclosed in, for example, Patent Documents 1 to 4. Xyloglucan, its hydrolyzate, carbohydrates such as porphyran hydrolyzate galactosulfate oligosaccharide, hesperetin, naringenin, etc., one kind known to affect lipid metabolism in vivo Or you may use it in combination with 2 or more types of components suitably, Furthermore, it is also free to combine with dietary fiber including the cellulose, pectin, and pullulan disclosed by the nonpatent literature 1. In addition to these components, flavonoids such as hesperidin, enzyme-treated hesperidin, naringin, enzyme-treated naringin, rutin, enzyme-treated rutin and proanthocyanidins, catechins such as catechin, epicatechin and epigallocatechin, and diacylglycerol It is known to be involved in the regulation of metabolism of lipids such as polyenephosphatidylcholine and other plant sterols, royal jelly, pravastatin sodium, simvastatin, simfibrate, nicotinic acid, nicomol, clinofibrate, clofibrate, pantethine, and riboflavin butyrate It is also possible to further enhance the in vivo lipid regulating effect by using one or more known components in combination.
また、コージオリゴ糖を有効成分として含有する本発明の生体内脂質調節剤は、そのままで、または必要に応じて、増量剤、賦形剤、結合剤などと混合して、顆粒、球状、短棒状、板状、立方体、錠剤など各種形状に成型して使用することも随意である。 Further, the in vivo lipid regulator of the present invention containing cordierigosaccharide as an active ingredient is used as it is or mixed with a bulking agent, excipient, binder, etc. It is also optional to use it in various shapes such as a rod, plate, cube, and tablet.
さらに、コージオリゴ糖を含有する本発明の生体内脂質調節剤は、酸味、塩から味、渋味、旨味、苦味などの他の呈味を有する各種物質とよく調和し、耐酸性、耐熱性も大きいので、一般の飲食物、医薬部外品、医薬品、飼料、餌料などの原料として有利に利用できる。そして、本発明の生体内脂質調節剤を配合した製品は、これを含有させない場合と同様に使用できる上に、これらの製品には生体内脂質調節作用が付与されていることから、ダイエットや、生活習慣病の予防、さらには肥満、糖尿病、高脂血症、脂肪肝などの治療や予防の目的で、カロリーや脂肪の摂取量を制限された生活習慣病者用の飲食品、医薬部外品、医薬品、その中間加工品や原材料として有利に利用できる。 Furthermore, the in vivo lipid regulator of the present invention containing cordierigosaccharide is well harmonized with various substances having other tastes such as acidity, salt to taste, astringency, umami, bitterness, acid resistance, heat resistance Therefore, it can be advantageously used as a raw material for general foods and drinks, quasi drugs, pharmaceuticals, feeds, feeds and the like. And the product which mix | blended the in-vivo lipid regulator of this invention can be used similarly to the case where this is not included, and since these products are provided with the in-vivo lipid control action, diet, Food / drinks for people with lifestyle-related diseases whose intake of calories and fat is restricted for the purpose of preventing lifestyle-related diseases, and also treating and preventing obesity, diabetes, hyperlipidemia, fatty liver, etc. It can be advantageously used as products, pharmaceuticals, intermediate processed products and raw materials.
また、本発明の生体内脂質調節剤は、例えば、調味料、複合調味料、各種の和菓子・洋菓子、パン、氷菓、シロップ、ペースト、野菜の加工食品、漬物、漬物の素、畜肉製品、魚介製品、珍味、惣菜食品、乳製品、清涼飲料水、各種プレミックス、即席食品、冷蔵食品、冷凍食品、チルド食品、レトルト食品、乾燥食品、さらには、離乳食、治療食、ドリンク剤、ペプチド食品、冷凍食品などの各種飲食物の製造に使用することができる。本発明の生体内脂質調節剤を配合したこれらの飲食品は、生体内脂質調節能が付与されているので、生体内脂質調節用の組成物として有利に利用できる。また、コージオリゴ糖を有効成分として含有する生体内脂質調節剤を、家畜、家禽、その他蜜蜂、蚕、淡水魚或いは海水魚、甲殻類などの飼育動物用の飼料、餌料、ペットフードなどに含有させて、これらに脂質調節機能を付与することも随意である。さらに、コージオリゴ糖は、整腸作用及び腸内の胆汁酸の再吸収を阻害する作用を有することから、本発明の生体内脂質調節剤を、整腸用及び／又は胆汁酸の代謝調節用として使用することも随意である。 The in vivo lipid regulator of the present invention includes, for example, seasonings, complex seasonings, various Japanese confectionery / Western confectionery, bread, ice confectionery, syrup, paste, processed vegetable foods, pickles, pickles, meat products, fish and shellfish Products, delicacies, prepared foods, dairy products, soft drinks, various premixes, instant foods, refrigerated foods, frozen foods, chilled foods, retort foods, dried foods, baby foods, therapeutic foods, drinks, peptide foods, It can be used for the production of various foods such as frozen foods. Since these foods and drinks containing the in vivo lipid regulator of the present invention are imparted with in vivo lipid regulating ability, they can be advantageously used as a composition for regulating in vivo lipids. In addition, in vivo lipid regulators containing koji oligosaccharides as active ingredients are included in feeds, feeds, pet foods, etc. for domestic animals, poultry, other bees, rabbits, freshwater fish, seawater fish, shellfish and other domestic animals. In addition, it is optional to impart a lipid regulating function to them. Furthermore, cordierigosaccharide has an intestinal regulating action and an action to inhibit the reabsorption of bile acids in the intestine. Therefore, the in vivo lipid regulator of the present invention is used for intestinal regulation and / or for bile acid metabolism regulation. It is also optional to use as.
本発明の生体内脂質調節剤を、対象とする組成物に含有させる方法としては、特に制限はなく、目的の組成物が完成されるまでに、或いは、完成品に対して、含有させればよく、その方法としては、例えば、混和、混捏、溶解、融解、分散、懸濁、乳化、浸透、晶出、散布、塗布、付着、噴霧、被覆（コーティング）、注入、晶出、固化などの公知のものが適宜に選ばれる。 There is no restriction | limiting in particular as a method of making the target lipid composition contain the in-vivo lipid regulator of this invention, If it makes it contain with respect to a finished product until the target composition is completed. Well, the methods include, for example, mixing, kneading, dissolving, melting, dispersing, suspending, emulsifying, penetrating, crystallization, spraying, applying, adhering, spraying, coating (coating), pouring, crystallization, solidification, etc. A well-known thing is chosen suitably.
さらに、本発明の生体内脂質調節剤の１日当たり必要な摂取量は、生体内脂質調節剤が、脂質の調節効果を発揮できる量であればよく、特に制限はないが、通常、体重１ｋｇ当たり、その有効成分であるコージオリゴ糖を、合計で、無水物換算で約０．５ｇ以上、望ましくは、約１．５ｇ以上、さらに望ましくは、約３．５ｇ以上が好適である。通常０．５ｇ未満では、脂質調節機能を効果的に発揮するには不充分である。また、本発明の生体内脂質調節剤の１日当たりの必要な摂取回数は、生体内脂質調節剤が、脂質の調節効果を発揮できる量のコージオリゴ糖を摂取できる回数であればよく、特に制限はなく、一度に一日の必要量の全量を摂取してもよいし、数回に分けて摂取してもよい。また、本発明の生体内脂質調節剤は、体質によっては、一度に摂取する量が多い場合に、おなかが緩くなる場合があるので、通常は、数回に分けて摂取するのが望ましく、とりわけ、食事の原材料として使用するか、食事と前後して摂取するのが望ましい。なお、本発明の生体内脂質調節剤は、通常、そのままで、或いは、飲食品、医薬品、医薬部外品などの組成物として経口的に摂取すればよく、それが不可能な場合には、カテーテルなどを使用して、直接、胃や腸管内に注入することも随意である。 Further, the daily intake amount of the in vivo lipid regulator of the present invention is not particularly limited as long as the in vivo lipid regulator can exert a lipid regulating effect, but usually, per kg body weight. The total amount of cordierigosaccharides as the active ingredient is preferably about 0.5 g or more, preferably about 1.5 g or more, more preferably about 3.5 g or more in terms of anhydride. Usually, if it is less than 0.5 g, it is insufficient to effectively exert the lipid regulating function. Further, the necessary number of intakes per day of the in vivo lipid regulator of the present invention may be any number of times that the in vivo lipid regulator can ingest an amount of cordigosaccharide that can exert a lipid regulating effect, and is particularly limited. No, you may take the whole amount of the daily requirement at once, or you may take it in several times. In addition, depending on the constitution, the in vivo lipid regulating agent of the present invention may be relaxed when the amount consumed at one time is large, so it is usually desirable to take it in several divided portions. It is desirable to use it as a raw material for meals or to be taken before or after meals. The in vivo lipid regulator of the present invention may be usually taken as it is or orally as a composition of food and drink, pharmaceuticals, quasi drugs, etc. Injecting directly into the stomach or intestinal tract using a catheter or the like is also optional.
以下、実験例に基づいて、コージオリゴ糖を使用した生体内脂質調節剤についてより詳細に説明する。 Hereinafter, the in vivo lipid regulator using cordierigosaccharide will be described in more detail based on experimental examples.
＜実験１：コージオリゴ糖及びその誘導体を含有する糖質の摂取がラットの生体内脂質に及ぼす影響＞
非特許文献３に開示されているとおり、コージオリゴ糖は、食物繊維作用を有することが知られていることから、生体に何らかの影響を与えていると考え、ラットの脂質代謝に着目して、これに及ぼす影響を調べる実験を、代表的な食物繊維のセルロースを含有する飼料及び、食物繊維を含有しない飼料を対照として、以下のように行った。
<Experiment 1: Effect of ingestion of carbohydrates containing cordierigosaccharide and its derivatives on lipids in rats>
As disclosed in Non-Patent Document 3, Koji oligosaccharide is known to have a dietary fiber action, so it is considered that it has some influence on the living body, and pays attention to lipid metabolism in rats, Experiments to examine the effect on this were carried out as follows using a diet containing cellulose as a representative dietary fiber and a diet containing no dietary fiber as controls.
＜ラットの飼育と体重の測定＞
体重１１０ｇ乃至１２０ｇのウイスター系ラット（日本チャールズリバー株式会社販売、雄、５週齢）５０匹を、表１に示す配合組成（％）の無繊維飼料で１週間馴化のために飼育した。馴化後、ラットを無作為に１０匹ずつ５群に分け、各々、表１に示す繊維質としてのセルロースを含まない飼料（以下、「無繊維飼料」という）、無繊維飼料にセルロースを５％含有させた飼料（以下、「有繊維飼料」という）、無繊維飼料に後述する実施例２の方法で調製した、糖組成としてコージオリゴ糖を９３％含有するシラップを噴霧乾燥した粉末（以下、コージオリゴ糖粉末と呼称する）を、無水物換算で２％、５％或いは１０％となるように配合した飼料の何れか１種を与えて、４週間の飼育試験を行った。有繊維飼料及び３種類のコージオリゴ糖粉末含有飼料は、セルロース或いはコージオリゴ糖粉末とコーンスターチとの合計の配合割合が、何れの飼料でも、飼料の総質量の４４．７５％となるように調製した。ラットの飼育は、室温２５℃で、１２時間の明暗サイクルとし、飼料及び水は、自由摂取とし、試験終了時に、各群の各々の個体の体重を計測して、各群の個体の平均体重と試験期間中の増加体重の平均を求めた。また、飼育試験期間の４週間に、各群のラット１匹当たりに与えた飼料の総量、及び、一日体重当たりのコージオリゴ糖粉末の平均摂取量を計算した。これらの結果を表２に示す。
＜血漿中の脂質の測定＞
試験終了後、ラットを１日絶食させ、下大静脈より１％ＥＤＴＡで処理した注射器を用いて血液を採取した。採取した血液を遠心分離（３，０００ｒｐｍ、１０分）して血漿を分離し、血漿中の総コレステロール、トリグリセリド、リン脂質の含量を、それぞれコレステロールＣ−テスト ワコー、トリグリセリド−テスト ワコー、リン脂質Ｃ−テスト ワコー（以上、何れも和光純薬株式会社販売）により測定した。その測定結果を表３に示す。有意差検定は有繊維飼料で飼育した群に対して行った。なお、非特許文献１に記載されているように、セルロースには経口摂取によりコレステロールを低減する機能は無いとされているので、コレステロールについては、有意差検定は無繊維飼料で飼育した群に対して行った。
＜臓器・組織の脂質の測定＞
前記採血後、ラットを解剖して、腸管膜周囲、腎臓周囲、睾丸周囲の各々の脂肪組織、肝臓、及び盲腸を取り出し、その各々の湿質量を測定した。脂肪組織重量の測定結果を表４に示す。肝臓についてはその湿質量、総脂質量、総コレステロール量、トリグリセリド量及びリン脂質量を測定した。その結果を表５に示す。なお、肝臓の脂質量は、採取した肝臓４質量部に対して脱イオン水４質量部を加えて、ホモジナイザーを使用してホモジナイズし、この８質量部に、クロロホルムとメタノールを２：１の容積比で混合した溶液２５ｍｌを加えて、撹拌抽出し、遠心分離（３，０００ｒｐｍ、１０分）した。この操作をさらに２回繰り返し、各操作で得られた遠心上清画分を集めてクロロホルム層を回収し、濃縮固化後、これのコレステロール、トリグリセリド、リン脂質量を、血漿中の脂質の測定と同じ方法により測定した。
＜盲腸内容物の質量及び盲腸内容物中の総胆汁酸量の測定＞
盲腸の内容物を取り出し、組織のみの重量を測定した。内容物を含む上記盲腸重量からこの値を差し引いて内容物重量とした。胆汁酸濃度の測定は、取り出した盲腸内容物０．２ｇにメタノールと水を８：２の比で混合した溶液２ｍｌを加えて、７０℃で３０分間抽出し、遠心分離（３，５００ｒｐｍ、１０分）した後、上清を五酸化リンの入ったデシケーター内で一晩乾燥させて乾固し、胆汁酸テスト ワコー（和光純薬株式会社販売）を用いて測定した。その結果を表６に示す。
<Rat breeding and body weight measurement>
Fifty Wistar rats (manufactured by Charles River Japan, male, 5 weeks old) weighing 110 g to 120 g were bred for 1 week of acclimatization with a fiber-free feed having the composition (%) shown in Table 1. After acclimatization, rats were randomly divided into 5 groups of 10 animals each, and each of the feeds not containing cellulose as a fiber shown in Table 1 (hereinafter referred to as “non-fiber feed”), 5% cellulose in the non-fiber feed Prepared feed (hereinafter referred to as “fiber feed”), powder prepared by spray-drying syrup containing 93% cordierigosaccharide as a sugar composition, prepared by the method of Example 2 described later in non-fiber feed (hereinafter referred to as “fiber feed”). A 4-week rearing test was conducted by feeding any one of the feeds containing 2%, 5% or 10% in terms of anhydride. Fiber feed and three types of Koji oligosaccharide powder-containing feed are prepared so that the total mixing ratio of cellulose or Koji oligosaccharide powder and corn starch is 44.75% of the total mass of the feed in any feed. did. Rats were raised at room temperature of 25 ° C., with a light / dark cycle of 12 hours, food and water were ad libitum, and at the end of the test, the weight of each individual in each group was measured, and the average weight of the individual in each group was measured. And the average weight gain during the study. In addition, during the four weeks of the breeding test period, the total amount of feed given to each rat in each group and the average intake of cordierigosaccharide powder per body weight per day were calculated. These results are shown in Table 2.
<Measurement of lipids in plasma>
After completion of the test, the rats were fasted for 1 day, and blood was collected from the inferior vena cava using a syringe treated with 1% EDTA. The collected blood is centrifuged (3,000 rpm, 10 minutes) to separate plasma, and the total cholesterol, triglyceride, and phospholipid content in the plasma is determined using cholesterol C-test Wako, triglyceride-test Wako, and phospholipid C, respectively. -Measured by Test Wako (all of which are sold by Wako Pure Chemical Industries, Ltd.). The measurement results are shown in Table 3. Significant difference tests were performed on groups fed with fiber feed. In addition, as described in Non-Patent Document 1, cellulose has no function of reducing cholesterol by ingestion, so for cholesterol, a significant difference test is performed on a group fed with a fiber-free feed. I went.
<Measurement of lipids in organs and tissues>
After the blood collection, the rats were dissected and the adipose tissue, liver, and cecum around the intestinal tract, the kidneys, and the testicles were removed, and the wet mass of each was measured. Table 4 shows the measurement results of the adipose tissue weight. For the liver, its wet mass, total lipid amount, total cholesterol amount, triglyceride amount and phospholipid amount were measured. The results are shown in Table 5. The amount of lipid in the liver was determined by adding 4 parts by mass of deionized water to 4 parts by mass of the collected liver and homogenizing using a homogenizer, and adding 8 parts by mass of chloroform and methanol to a volume of 2: 1. 25 ml of the solution mixed at a ratio was added, extracted with stirring, and centrifuged (3,000 rpm, 10 minutes). Repeat this operation two more times, collect the centrifugal supernatant fractions obtained in each operation, collect the chloroform layer, concentrate and solidify, and then measure the cholesterol, triglyceride and phospholipid levels in the plasma lipids. It was measured by the same method.
<Measurement of mass of cecal contents and total bile acid amount in cecal contents>
The contents of the cecum were removed and the weight of the tissue alone was measured. This value was subtracted from the cecal weight including the content to obtain the content weight. The bile acid concentration was measured by adding 2 ml of a solution in which methanol and water were mixed at a ratio of 8: 2 to 0.2 g of the cecal contents taken out, extracted at 70 ° C. for 30 minutes, and centrifuged (3,500 rpm, 10 Then, the supernatant was dried overnight in a desiccator containing phosphorus pentoxide and dried, and measured using a bile acid test Wako (available from Wako Pure Chemical Industries, Ltd.). The results are shown in Table 6.
＜コージオリゴ糖の体重及び摂餌量に及ぼす影響＞
表２から明らかなように、コージオリゴ糖粉末を５％或いは１０％含有する飼料で飼育した群で、有繊維飼料で飼育した群と比べて、有意の体重差及び体重増加の抑制が認められた。コージオリゴ糖粉末を５％或いは１０％含有する飼料で飼育した群は、他の群より試験期間中の総飼料摂取量も少なかった。試験期間中における飼料利用効率（摂取した飼料１ｇあたりの体重増加量）は、コージオリゴ糖粉末を１０％含有する飼料で飼育した群では他の群より有意に小さかった。一方、飼料中のセルロースやコージオリゴ糖の量を差し引いて求めた正味の飼料利用効率には５つの群の間で差が認められなかった。したがって、コージオリゴ糖は、摂取による体重増加への寄与の小さい糖質であることが明らかとなった。
＜コージオリゴ糖の脂質に及ぼす影響＞
表３から明らかなように、血漿中の脂質については、コージオリゴ糖粉末を１０％含有する飼料で飼育した群で、無繊維飼料で飼育した群と比べて、有意の総コレステロール量の低下が認められ、また、有繊維飼料で飼育した群と比べて、有意のトリグリセリド量の低下が認められた。リン脂質は、コージオリゴ糖摂取群において、摂取量の増大とともに低下する傾向が認められたものの、有意な差は認められなかった。表４から明らかなように、コージオリゴ糖粉末を５％又は１０％含有する飼料で飼育した群で、有繊維飼料で飼育した群と比べて、腸管周囲脂肪、腎周囲脂肪、睾丸周囲脂肪の蓄積が、何れも有意に抑制されていた。また、コージオリゴ糖粉末を２％含有する飼料で飼育した群で、有繊維飼料で飼育した群と比べて、睾丸周囲脂肪の蓄積が有意に抑制されていた。表５から明らかなように、肝臓の総脂肪量及びトリグリセリド量は、コージオリゴ糖粉末を５％又は１０％含有する飼料で飼育した群で、有繊維飼料で飼育した群と比べて有意の低下が認められた。また、表５には示していないけれども、コージオリゴ糖粉末を５％又は１０％含有する飼料で飼育した群と無繊維飼料で飼育した群との間で有意差検定をおこなったところ、有意の差は認められなかった。一方、その他の脂質については有意の差は認められなかった。
＜コージオリゴ糖の盲腸内容物及び盲腸内の胆汁酸に及ぼす影響＞
表６から明らかなように、コージオリゴ糖粉末を５％或いは１０％含有する飼料で飼育した群で、有繊維飼料で飼育した群と比べて、盲腸内容物及び盲腸内胆汁酸量の有意の増加が認められ、コージオリゴ糖粉末を２％含有する飼料で飼育した群では、有繊維飼料で飼育した群と比べて、盲腸内胆汁酸量の有意の増加が認められた。
<Effect of cordierigosaccharide on body weight and food intake>
As is clear from Table 2, in the group bred with feed containing 5% or 10% cordierigosaccharide powder, a significant difference in body weight and suppression of weight gain were observed compared to the group bred with fiber diet. It was. Groups fed with feed containing 5% or 10% cordierigosaccharide powder also had less total feed intake during the test period than the other groups. The feed utilization efficiency (weight gain per gram of ingested feed) during the test period was significantly lower in the group fed with feed containing 10% cordierigosaccharide powder than in the other groups. On the other hand, there was no difference among the five groups in the net feed utilization efficiency determined by subtracting the amounts of cellulose and cordierigosaccharides in the feed. Therefore, it has been clarified that cordierigosaccharide is a carbohydrate having a small contribution to weight gain by ingestion.
<Effect of Koji oligosaccharide on lipid>
As can be seen from Table 3, for the lipids in plasma, there was a significant reduction in total cholesterol in the group fed with 10% cordierigosaccharide powder compared to the group fed with no fiber feed. In addition, a significant decrease in the amount of triglyceride was observed compared to the group fed with a fiber feed. Phospholipids showed a tendency to decrease as the intake increased in the Koji oligosaccharide intake group, but no significant difference was observed. As is apparent from Table 4, in the group bred with feed containing 5% or 10% cordierigosaccharide powder, compared to the group bred with fiber feed, peri-intestinal fat, peri-renal fat, and testicular fat Accumulation was significantly suppressed in all cases. Further, in the group bred with feed containing 2% cordierigosaccharide powder, the accumulation of testicular fat was significantly suppressed compared to the group bred with fiber feed. As is apparent from Table 5, the total fat content and triglyceride content of the liver were significantly decreased in the group bred with feed containing 5% or 10% cordierigosaccharide powder compared to the group bred with fiber feed. Was recognized. In addition, although not shown in Table 5, a significant difference test was performed between a group fed with a feed containing 5% or 10% cordierigosaccharide powder and a group fed with a non-fiber feed. There was no difference. On the other hand, no significant difference was observed for other lipids.
<Effect of cordierigosaccharide on cecal contents and bile acids in the cecum>
As can be seen from Table 6, the cecal contents and the amount of bile acid in the cecum were significantly higher in the group bred with feed containing 5% or 10% cordierigosaccharide powder than in the group bred with fiber diet. An increase was observed, and a significant increase in the amount of bile acid in the cecum was observed in the group fed with a diet containing 2% cordierigosaccharide powder compared to the group fed with a fiber diet.
これらの結果から、コージオリゴ糖が、血漿中のトリグリセリド、臓器周辺の脂質（内臓脂肪）などの脂質調節作用を有しており、これらの作用が代表的な食物繊維のセルロースの持つ作用よりも遥かに強いことが明らかになった。特に、血漿中のトリグリセリド、内臓周囲の脂質に対しては、著しい脂質調節効果があり、また、肝臓のトリグリセリドも低下傾向を示したことから、血漿中の脂質の低下が、トリグリセリドを脂肪組織に蓄積する機構によるものではなく、コージオリゴ糖を摂取したラットでは、生体内の脂質そのものが減少していることを示している。また、この生体内の脂質が低減する脂質調節作用は、コージオリゴ糖の摂取量に依存しており、脂質の種類による程度差はあるものの、コージオリゴ糖粉末を２％含有する飼料（コージオリゴ糖の１日の平均摂取量が、体重１ｋｇ当たり１．４ｇ）で既に低減効果が認められ、コージオリゴ糖粉末を５％以上含有する場合（コージオリゴ糖の１日の平均摂取量が、体重１ｋｇ当たり３．５ｇ以上）では顕著な調節作用があることが確認された。また、脂質の吸収への関与が知られている胆汁酸量が、盲腸内で増加していることから、コージオリゴ糖が胆汁酸の小腸での再吸収を阻害し、それに伴う、小腸での脂質の吸収が抑制されている可能性が高く、コージオリゴ糖による脂質調節機構の一つが、胆汁酸の小腸での再吸収の阻害によることが示唆された。 From these results, Koji oligosaccharide has lipid regulating action such as triglyceride in plasma, lipid around organ (visceral fat), etc., and these actions are more than the action of cellulose of typical dietary fiber It became clear that it was far stronger. In particular, triglycerides in plasma and lipids surrounding viscera have a significant lipid-regulating effect, and liver triglycerides also showed a tendency to decrease. This is not due to the accumulation mechanism, but it is shown that the lipid itself in the living body is decreased in the rats ingesting the cordigosaccharide. In addition, the lipid regulating action to reduce the lipids in the living body depends on the amount of Koji oligosaccharide intake, and although there is a difference in the degree depending on the type of lipid, feed containing Koji oligosaccharide powder (Koji Oligosaccharide). When the average daily intake of sugar is already 1.4 g per kg of body weight), a reduction effect has already been observed, and when the Koji oligosaccharide powder contains 5% or more (the average daily intake of Koji oligosaccharide is It was confirmed that there is a remarkable regulating action at 3.5 g or more per kg). In addition, since the amount of bile acid, which is known to be involved in lipid absorption, is increased in the cecum, Koji oligosaccharide inhibits reabsorption of bile acids in the small intestine, and accompanying this, Lipid absorption is highly likely to be suppressed, suggesting that one of the lipid regulation mechanisms by cordierigosaccharide is inhibition of reabsorption of bile acids in the small intestine.
なお、具体的なデータは示さないが、５％のコージオリゴ糖粉末を含有する飼料で飼育したラットの１０匹の内４匹で、また、１０％のコージオリゴ糖粉末を含有する飼料で飼育したラットの１０匹の内１０匹でコージオリゴ糖の摂取開始の翌日から４〜５日間軟便を生じ、その後回復した。このことは、コージオリゴ糖が難消化性であることを示しており、同じ出願人らが、非特許文献３において開示した内容と一致している。また、２％のコージオリゴ糖粉末を含有する飼料の摂取では軟便が発生せず、１０％のコージオリゴ糖粉末を含有する飼料を摂取した群でも摂取を継続すると軟便が改善することから、腸内菌叢の馴化が徐々に進行していることを示している。 Although specific data are not shown, 4 out of 10 rats fed with a diet containing 5% cordierigosaccharide powder, and fed with a diet containing 10% cordieroligosaccharide powder. Ten of the 10 rats developed loose stools for 4-5 days from the day after the start of ingestion of cordierigosaccharide, and then recovered. This indicates that the cord oligosaccharide is indigestible, and is consistent with the content disclosed in Non-Patent Document 3 by the same applicants. Ingestion of feed containing 2% cordierigosaccharide powder does not cause loose stool, and even in the group that has consumed feed containing 10% cordieroligosaccharide powder, continuous ingestion improves loose stool. It shows that acclimatization of the internal flora is gradually progressing.
以上の実験結果から、コージオリゴ糖は、生体内の脂質調節に利用できることが判明した。 From the above experimental results, it was found that Koji oligosaccharide can be used for lipid regulation in vivo.
以下に、本発明のコージオリゴ糖を有効成分として含有する生体内脂質調節剤と、これを配合してなる組成物の例を、以下の実施例で具体的に説明する。しかし、本発明はこれらの実施例によって限定されるものではない。 Hereinafter, examples of the in vivo lipid regulator containing the cordierigosaccharide of the present invention as an active ingredient and a composition comprising the same will be specifically described in the following examples. However, the present invention is not limited to these examples.
＜コージオリゴ糖を有効成分として含有する生体内脂質調節剤＞
特許文献５の実施例Ａ−１１に開示された方法に準じて、コージビオースとスクロースから、濃度７５％、固形物当たり約５５％のコージビオシルフラクトシドを含有するシラップ状の生体内脂質調節剤を調製した。本品は、そのままで、或いは、これを、可食材料、医薬材料、飼餌材料などの原材料、又は、中間製品などに含有させることにより、脂質調節用の飲食物、医薬部外品、医薬品、飼料、餌料などの組成物の調製に有利に利用できる。
<In vivo lipid regulator containing cordierigosaccharide as active ingredient>
According to the method disclosed in Example A-11 of Patent Document 5, a syrup-like in vivo lipid regulator containing cordierbiosyl fructoside at a concentration of 75% and a solid content of about 55% from cordobiose and sucrose Was prepared. This product is used as it is, or by incorporating it into raw materials such as edible materials, pharmaceutical materials, feeding materials, or intermediate products, foods and drinks for regulating lipids, quasi drugs, pharmaceuticals It can be advantageously used for preparing compositions such as feeds and feeds.
特許文献５の実施例Ａ−１５に開示された方法に準じて（但し、マルトースホスホリラーゼの代わりにトレハロースホスホリラーゼを使用する）、トレハロースを原料としてコージオリゴ糖含有シラップを調製した。本糖液のコージオリゴ糖含有率を高めるため、特許文献５の実施例Ａ−１０に開示された方法に従ってカラムクロマトグラフィーを行い、コージオリゴ糖高含有画分を採取した。更に、精製、濃縮して、濃度８１％、固形物当たり、グルコース０．１％、トレハロース６．２％、コージビオース０．７％、コージトリオース１２．７％、セラギノース（コージビオシルグルコシド）７１．４％、コージテトラオース４．０％、コージトリオシルグルコシド４．４％及びその他の糖質０．５％を含有するシラップ状の生体内脂質調節剤を得た。本品は、そのままで、或いは、これを、可食材料、医薬材料、飼餌材料などの原材料、又は、中間製品などに含有させることにより、脂質調節用の飲食物、医薬部外品、医薬品、飼料、餌料などの組成物の調製に有利に利用できる。 In accordance with the method disclosed in Example A-15 of Patent Document 5 (however, trehalose phosphorylase is used instead of maltose phosphorylase), cordierigosaccharide-containing syrup was prepared using trehalose as a raw material. In order to increase the content of cordierigosaccharide in the sugar solution, column chromatography was performed according to the method disclosed in Example A-10 of Patent Document 5, and a fraction containing cordieroligosaccharide was collected. Furthermore, it refine | purifies and concentrates, Concentration 81%, Per solid, Glucose 0.1%, Trehalose 6.2%, Codybiose 0.7%, Cody triose 12.7%, Seraginose (Codybiosyl glucoside) 71 A syrup-like in vivo lipid regulator containing 0.4%, Koji tetraose 4.0%, Koji triosyl glucoside 4.4% and other carbohydrates 0.5% was obtained. This product is used as it is, or by incorporating it into raw materials such as edible materials, pharmaceutical materials, feeding materials, or intermediate products, foods and drinks for regulating lipids, quasi drugs, pharmaceuticals It can be advantageously used for preparing compositions such as feeds and feeds.
＜脂質調節用テーブルシュガー＞
実施例２の方法で調製したコージオリゴ糖含有シラップを噴霧乾燥して得た粉末状の脂質調節剤５０質量部に対して、無水結晶マルチトール４６質量部、糖転移ヘスペリジン（東洋精糖株式会社販売、商品名「αＧヘスペリジン」）３質量部、スクラロース（三栄源エフ・エフ・アイ株式会社販売）１質量部を２００質量部の水に溶解し、常法により噴霧乾燥して脂質調節用の粉末甘味料を調製した。本品は、コージオリゴ糖及び糖転移ヘスペリジンが体内の脂質調節をすることから、ダイエットの目的や、生活習慣病の予防、或いは、脂質の摂取を制限された肥満、高脂血症などの生活習慣病の患者用のテーブルシュガーとして好適である。
<Table sugar for lipid regulation>
With respect to 50 parts by mass of a powdery lipid regulator obtained by spray-drying the cordyoligosaccharide-containing syrup prepared by the method of Example 2, 46 parts by mass of anhydrous crystalline maltitol, sugar-transferred hesperidin (sold by Toyo Seika Co., Ltd.) , Trade name "αG Hesperidin") 3 parts by weight, 1 part by weight of sucralose (sold by San-Ei Gen FFI Co., Ltd.) is dissolved in 200 parts by weight of water and spray-dried by a conventional method to prepare a lipid-controlling powder A sweetener was prepared. This product is made of cordierigosaccharide and transglycosyl hesperidin that regulates lipids in the body, so it can be used for diet purposes, prevention of lifestyle-related diseases, or life such as obesity and hyperlipidemia with restricted lipid intake. It is suitable as a table sugar for patients with habitual diseases.
＜脂質調節用野菜ジュース＞
市販野菜ジュース９７．５質量部に、キシログルカン部分分解物１質量部、実施例１で調製したシラップ状の脂質調節剤１質量部、糖転移ナリンジン０．５質量部を加えて混合し、脂質調節用の野菜ジュースを調製した。本品は、コージビオシルフラフトシド、キシログルカン部分分解物、糖転移ナリンジン及び野菜由来の食物繊維を含有しているので、本品、或いは、本品を用いて調製する飲食品、飼料、餌料などを摂取すると、体内の脂質調節がされることから、ダイエットの目的や、生活習慣病の予防、或いは、脂質の摂取を制限された肥満、高脂血症などの生活習慣病の患者用の健康補助食品として好適である。
<Vegetable juice for lipid regulation>
To 97.5 parts by mass of commercially available vegetable juice, 1 part by mass of a xyloglucan partial degradation product, 1 part by mass of a syrup-like lipid regulator prepared in Example 1, and 0.5 parts by mass of glycosylated naringin were added and mixed to obtain a lipid. A vegetable juice for conditioning was prepared. This product contains Kojibiosyl fraftside, xyloglucan partial degradation products, sugar-transferred naringin, and vegetable-derived dietary fiber, so this product, or foods, beverages, feeds and feeds prepared using this product Ingestion etc. regulates lipids in the body, so it is intended for diet, prevention of lifestyle-related diseases, or for patients with lifestyle-related diseases such as obesity and hyperlipidemia with restricted lipid intake Suitable as a health supplement.
＜脂質調節用の錠剤＞
ガンマ−オリザノール２００質量部に対して、実施例２の方法で調製したコージオリゴ糖含有シラップを噴霧乾燥して得た粉末状の脂質調節剤６５０質量部、糖転移ヘスペリジン５０質量部、ステアリン酸マグネシウム２質量部を均一に混合し、常法により打錠して、１錠が２５０ｍｇの錠剤を調製した。本品は、ガンマ−オリザノール、コージオリゴ糖及び糖転移ヘスペリジンが体内の脂質調節をすることから、肥満、脂肪肝、高脂血症などの患者用の脂質調節剤として好適である。
<Tablets for lipid control>
650 parts by weight of a powdery lipid regulator obtained by spray-drying the cordyoligosaccharide-containing syrup prepared by the method of Example 2 with respect to 200 parts by weight of gamma-oryzanol, 50 parts by weight of glycosylated hesperidin, magnesium stearate Two parts by mass were uniformly mixed, and tableted by a conventional method to prepare tablets each having 250 mg. This product is suitable as a lipid regulator for patients with obesity, fatty liver, hyperlipidemia and the like because gamma-oryzanol, cordierigosaccharide and glycosylated hesperidin regulate lipids in the body.
以上説明したとおり、本発明は、ヒトを含む動物の生体内の脂質調節に使用することのできる、コージオリゴ糖を有効成分として含有する生体内脂質調節剤、及び、この生体内脂質調節剤を配合してなる組成物に関するものである。しかも、コージオリゴ糖は、経口摂取しても安全で、且つ、非常に安定であることから、本発明によるコージオリゴ糖を有効成分として含有する生体内脂質調節剤は、飲食品、化粧品、医薬部外品、医薬品など多岐の分野に渡り利用することができる。本発明は、この様に顕著な作用効果を有する発明であり、産業上の貢献は誠に大きく、意義のある発明である。
As described above, the present invention provides an in vivo lipid regulator containing cordierigosaccharide as an active ingredient that can be used for lipid regulation in animals including humans, and the in vivo lipid regulator. It is related with the composition formed by mix | blending. In addition, since cordierigosaccharides are safe even when ingested and are very stable, the in vivo lipid regulator containing cordierigosaccharides according to the present invention as an active ingredient is used in foods, beverages, cosmetics, and pharmaceuticals. It can be used in various fields such as quasi-drugs and pharmaceuticals. The present invention is an invention having such a remarkable function and effect, and is a significant invention that has a significant industrial contribution.
Claims (7)
A composition comprising the in vivo lipid regulator according to any one of claims 1 to 6, which is in the form of any one of pharmaceuticals, quasi drugs, health foods, foods and drinks, feeds, and feeds.
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| JPWO2007114499A1 (en) * | 2006-03-31 | 2009-08-20 | 明治乳業株式会社 | Anti-fat accumulation composition |
| JP2011173798A (en) * | 2010-02-23 | 2011-09-08 | Yakult Honsha Co Ltd | Agent for reducing mesenteric fat |
| JP2013134129A (en) * | 2011-12-26 | 2013-07-08 | Lion Corp | Method for determining dyslipidemia |
| JPWO2014133060A1 (en) * | 2013-03-01 | 2017-02-02 | 株式会社林原 | Anti-lifestyle disease agent and oral composition comprising the same |
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| JPH10304882A (en) * | 1996-11-08 | 1998-11-17 | Hayashibara Biochem Lab Inc | Kojibiose phosphorylase, its production and use |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH10304882A (en) * | 1996-11-08 | 1998-11-17 | Hayashibara Biochem Lab Inc | Kojibiose phosphorylase, its production and use |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2007114499A1 (en) * | 2006-03-31 | 2009-08-20 | 明治乳業株式会社 | Anti-fat accumulation composition |
| JP2011173798A (en) * | 2010-02-23 | 2011-09-08 | Yakult Honsha Co Ltd | Agent for reducing mesenteric fat |
| JP2013134129A (en) * | 2011-12-26 | 2013-07-08 | Lion Corp | Method for determining dyslipidemia |
| JPWO2014133060A1 (en) * | 2013-03-01 | 2017-02-02 | 株式会社林原 | Anti-lifestyle disease agent and oral composition comprising the same |
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