JP5121308B2 - Composition for preventing, improving or treating metabolic syndrome - Google Patents
Composition for preventing, improving or treating metabolic syndrome Download PDFInfo
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- JP5121308B2 JP5121308B2 JP2007141154A JP2007141154A JP5121308B2 JP 5121308 B2 JP5121308 B2 JP 5121308B2 JP 2007141154 A JP2007141154 A JP 2007141154A JP 2007141154 A JP2007141154 A JP 2007141154A JP 5121308 B2 JP5121308 B2 JP 5121308B2
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- Prior art keywords
- carnitine
- composition
- fat
- caffeine
- arginine
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Description
本発明は生体内における脂肪の合成を抑制する働き、および脂肪の分解を促進する働き、さらには効果的に脂肪を燃焼する働きのある組成物であって、メタボリックシンドローム、脂質代謝異常(例えば脂肪肝、高脂血症)または肥満(例えば内臓脂肪蓄積、皮下脂肪蓄積)の予防、改善または治療作用を有する組成物およびそれらを含有してなる飲食品または医薬品に関する。 The present invention is a composition having a function of suppressing fat synthesis in a living body, a function of accelerating the degradation of fat, and a function of effectively burning fat, and has metabolic syndrome, lipid metabolism abnormality (for example, fat The present invention relates to a composition having an effect of preventing, improving or treating liver, hyperlipidemia) or obesity (for example, visceral fat accumulation, subcutaneous fat accumulation), and a food or drink or a medicine containing them.
近年、肥満は増加の一途を辿っており、WHO、世界保健機関は肥満に関わる糖尿病、高脂血症、高血圧、動脈硬化、脂肪肝などの生活習慣病のリスクの増大に対して世界各国に警告を発している。内臓脂肪の蓄積をベースに、糖代謝異常(耐糖能異常、糖尿病)、脂質代謝異常(高中性脂肪血症、高コレステロール血症または低HDLコレステロール血症などの高脂血症)、高血圧などの動脈硬化のリスクファクター(危険因子)が複数重なった状態をメタボリックシンドローム(代謝症候群)という。健康診断などで血糖値や血圧が「要注意」程度の軽度な異常でも重複すると心血管病になりやすく、肥満、高血圧、高血糖、高中性脂肪血症、または高コレステロール血症の危険因子を全く持たないヒトに比べて、2つ持つヒトは心臓病のリスクが10倍に、3〜4つ持つヒトはリスクが31倍になると言われている。肥満・糖尿病・高血圧・高脂血症を全て発症すると心筋梗塞や脳梗塞を発症する確率が高くなるので「死の四重奏」とも呼ばれている。最終的に心筋梗塞や脳梗塞など心血管病に至るのは、内臓脂肪の蓄積が根本的な原因と考えられており、内臓脂肪の蓄積を減少させることがメタボリックシンドローム、脂質代謝異常(例えば脂肪肝、高脂血症)、並びに心血管病の予防・改善のために重要である。肥満はエネルギーの出納バランスが崩れることによって起こるため、肥満の抑制には摂取エネルギーを減少させるだけではなく、基礎代謝や活動代謝の消費エネルギーを増加させることが重要である。摂取エネルギーを減少させるためには、脂肪や糖質をよりエネルギーの少ない代替品に代えるといった工夫がなされてはいるが、食品としての味や加工性の点で必ずしも十分な成果が得られていない。 In recent years, obesity has continued to increase, and WHO and the World Health Organization are in the world to increase the risk of lifestyle-related diseases such as diabetes, hyperlipidemia, hypertension, arteriosclerosis and fatty liver related to obesity. A warning has been issued. Based on the accumulation of visceral fat, abnormal glucose metabolism (abnormal glucose tolerance, diabetes), abnormal lipid metabolism (hyperlipidemia such as hypertriglyceremia, hypercholesterolemia or low HDL cholesterolemia), hypertension, etc. A state in which multiple risk factors for atherosclerosis overlap is called metabolic syndrome (metabolic syndrome). Even if a mild abnormality such as a blood glucose level or blood pressure is necessary for medical checkups, it can easily lead to cardiovascular disease. Risk factors for obesity, hypertension, hyperglycemia, hypertriglyceridemia, or hypercholesterolemia It is said that a human with two has a 10-fold risk of heart disease and a human with 3-4 has a 31-fold risk compared to a human who has none. When all obesity, diabetes, hypertension, and hyperlipidemia develop, the probability of developing myocardial infarction or cerebral infarction increases, so it is also called “death quartet”. The ultimate cause of cardiovascular diseases such as myocardial infarction and cerebral infarction is thought to be the underlying cause of visceral fat accumulation. Decreasing visceral fat accumulation may result in metabolic syndrome, abnormal lipid metabolism (eg, fat It is important for the prevention and improvement of liver, hyperlipidemia) and cardiovascular disease. Obesity occurs when the balance of energy balance is lost. Therefore, in order to suppress obesity, it is important not only to reduce the energy intake, but also to increase the energy consumed in basal metabolism and activity metabolism. In order to reduce the intake energy, measures such as replacing fat and sugar with alternatives with less energy have been made, but sufficient results have not been obtained in terms of taste and processability as food. .
肥満を解消するには余分なカロリーを摂取しないで、運動エネルギー源として体脂肪をできるだけ多く消費すればよい。しかし、一般に肥満気味の人は正常の人に比べて脂肪の分解が遅く且つ少ない傾向にあり、同じ運動を行っても糖質の分解が先行して体脂肪はあまり消費されない。そこで、より効果的に脂肪を分解し、その脂肪を消費するような組成物およびそれを含む飲食品、医薬品の開発が望まれていた。 To eliminate obesity, you should not consume extra calories and consume as much body fat as a source of kinetic energy. However, in general, obese people tend to decompose fat slowly and less than normal people, and even if the same exercise is performed, carbohydrate decomposition precedes and body fat is not consumed much. Therefore, development of a composition that breaks down fat more effectively and consumes the fat, and foods and drinks and pharmaceuticals containing the composition have been desired.
肥満予防の方策はいろいろ提唱されているが、近年、我々が日常的に摂取する様々な食品中に脂質代謝の改善、肥満の予防あるいは改善作用をもつ成分が見出され、肥満予防に役立つのではないかと期待されている。本発明者らは、その様な作用をもつ食品成分の中で、アルギニン、カフェイン、イソフラボンおよびカルニチンの作用メカニズムが異なる素材の生理作用に着目した。アルギニンはグルカゴンや成長ホルモンの分泌促進作用を介して脂質代謝を促進し、肝臓の脂肪合成を抑制して肥満改善作用を示す。カフェインはアデノシンレセプターへのアンタゴニスト作用、血中カテコールアミンレベルの増加作用およびホスホジエステラーゼ活性の阻害作用を介して脂質代謝を促進し、肝臓の脂肪合成を抑制し、さらに、安静時代謝率やエネルギー消費量を増加することにより、体脂肪量や体重を減少させることが知られている。イソフラボンはエストロゲン作用を介して脂肪細胞の分化や脂質代謝を促進し、脂肪酸酸化酵素カルニチン・パルミトイルトランスフェラーゼ1型を活性化して抗肥満作用を示す。カルニチンはミトコンドリアへの脂肪酸の取り込みを促進し、脂肪酸代謝(β酸化)を促進することにより抗肥満作用を示す。 Various measures for the prevention of obesity have been proposed, but in recent years, ingredients that improve lipid metabolism and prevent or improve obesity have been found in various foods that we ingest daily. It is expected that. The present inventors paid attention to the physiological action of materials having different action mechanisms of arginine, caffeine, isoflavone and carnitine among food ingredients having such actions. Arginine promotes lipid metabolism through the action of promoting the secretion of glucagon and growth hormone, and suppresses liver fat synthesis, thereby improving obesity. Caffeine promotes lipid metabolism through an antagonistic action on adenosine receptors, an increase in blood catecholamine level and an inhibitory action on phosphodiesterase activity, suppresses liver fat synthesis, and further, resting metabolic rate and energy consumption It is known to decrease body fat mass and body weight by increasing. Isoflavone promotes adipocyte differentiation and lipid metabolism through estrogen action, and activates fatty acid oxidase carnitine / palmitoyltransferase type 1 to exhibit anti-obesity action. Carnitine exhibits an anti-obesity effect by promoting fatty acid uptake into mitochondria and promoting fatty acid metabolism (β oxidation).
上記のように、これらの各成分が単独で脂質代謝に作用があることは公知である。さらには、これら2成分を併用すると抗肥満作用を示すことが知られている。たとえば、アルギニンとカフェインの混合物は脂肪分解を促進して脂肪代謝改善作用を有することや(特許文献1)、大豆イソフラボンの1種であるゲニステインを含有する組成物にカルニチンを加えるとカルニチン・パルミトイルトランスフェラーゼ1型遺伝子の発現が相乗的に増加すること(特許文献2)が明らかにされている。 As described above, it is known that each of these components alone has an effect on lipid metabolism. Furthermore, it is known that when these two components are used in combination, an anti-obesity effect is exhibited. For example, a mixture of arginine and caffeine has an action of improving fat metabolism by promoting lipolysis (Patent Document 1), and when carnitine is added to a composition containing genistein, which is a kind of soybean isoflavone, carnitine palmitoyl It has been clarified that the expression of the transferase type 1 gene increases synergistically (Patent Document 2).
しかし、これら4成分(すなわち、アルギニン、カフェイン、イソフラボン、カルニチン)を組み合わせた報告はない。
肥満を予防・解消するため、摂取カロリーを制限する食事療法、運動療法、食欲抑制剤による薬物療法などが行われている。しかし、食事療法は過度な制限食であることが多く、煩雑なカロリー計算と強固な意志を必要とし、個人で長期間管理するには困難が伴う。また、運動療法は精神的にも肉体的にも苦痛を伴い、多忙な現代社会においては長期間継続するのは非常に困難である。運動エネルギー源として体脂肪をできるだけ多く消費することは有効であるが、肥満傾向にあるものは脂肪代謝が緩慢であり、運動によっても体脂肪を減少させることが難しい。したがって、肝臓中での脂肪合成を抑制し、脂肪細胞中に蓄積する脂肪の分解を促進し、また、脂肪を効果的に燃焼することにより、肥満の予防、改善または治療に寄与し得る組成物およびそれを含有する飲食品、医薬品の開発が望まれていた。 In order to prevent and eliminate obesity, diet therapy, exercise therapy, and pharmacotherapy with an appetite suppressant are used to limit calorie intake. However, dietary therapy is often an excessively restricted diet, requiring complicated calorie calculation and strong will, and is difficult to manage for a long period of time by an individual. Exercise therapy is both mentally and physically painful, and it is very difficult to continue for a long time in a busy modern society. It is effective to consume as much body fat as a source of kinetic energy, but those that tend to be obese have slow fat metabolism, and it is difficult to reduce body fat even by exercise. Therefore, a composition that can contribute to the prevention, improvement or treatment of obesity by suppressing fat synthesis in the liver, promoting degradation of fat accumulated in fat cells, and effectively burning fat. Development of foods and drinks and pharmaceuticals containing the same has been desired.
本発明は、上記問題点に鑑みてなされたものであり、その目的はメタボリックシンドローム、脂質代謝異常(例えば脂肪肝、高脂血症)または肥満(例えば内臓脂肪蓄積、皮下脂肪蓄積)の予防、改善または治療組成物およびそれらを含有する飲食品または医薬品などを提供することにある。 The present invention has been made in view of the above problems, and its purpose is prevention of metabolic syndrome, lipid metabolism abnormality (eg, fatty liver, hyperlipidemia) or obesity (eg, visceral fat accumulation, subcutaneous fat accumulation), An object of the present invention is to provide an improved or therapeutic composition and a food or drink or pharmaceutical containing the same.
本発明者らは、前記課題を解決すべく鋭意研究を行ったところ、アルギニン・カフェイン・イソフラボン類・カルニチンの4成分を含有する組成物が糖尿病モデル動物において意外にも強い脂質代謝異常の改善作用、抗肥満作用を有することを見いだし、さらに検討を重ねて本発明を完成するに至った。 As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a composition containing four components of arginine, caffeine, isoflavones, and carnitine is unexpectedly improved in abnormal lipid metabolism in diabetes model animals. It has been found that it has an action and an anti-obesity action, and has been further studied to complete the present invention.
すなわち、本発明は
(1)グルカゴン分泌亢進作用を有するアミノ酸類の少なくとも1種、キサンチン誘導体の少なくとも1種、イソフラボン類の少なくとも1種、およびカルニチン類もしくはカルニチン前駆体の少なくとも1種を含有してなるメタボリックシンドロームの予防、改善または治療組成物、
(2)グルカゴン分泌亢進作用を有するアミノ酸類の少なくとも1種、キサンチン誘導体の少なくとも1種、イソフラボン類の少なくとも1種、およびカルニチン類もしくはカルニチン前駆体の少なくとも1種を含有してなる脂質代謝異常の予防、改善または治療組成物、
(3)脂質代謝異常が脂肪肝である前記(2)に記載の脂質代謝異常の予防、改善または治療組成物、
(4)脂質代謝異常が高コレステロール血症である前記(2)に記載の脂質代謝異常の予防、改善または治療組成物、
(5)脂質代謝異常が高中性脂肪血症である前記(2)に記載の脂質代謝異常の予防、改善または治療組成物、
(6)グルカゴン分泌亢進作用を有するアミノ酸類の少なくとも1種、キサンチン誘導体の少なくとも1種、イソフラボン類の少なくとも1種、およびカルニチン類もしくはカルニチン前駆体の少なくとも1種を含有してなる肥満の予防、改善または治療組成物、
(7)肥満が内臓脂肪および/または皮下脂肪に起因するものである前記(6)記載の肥満の予防、改善または治療組成物、
(8)グルカゴン分泌亢進作用を有するアミノ酸類が、アルギニン、アラニン、ロイシンまたはそれらの医薬もしくは食品として許容される塩である前記(1)〜(7)のいずれかに記載の予防、改善または治療組成物、
(9)キサンチン誘導体が、カフェイン、テオフィリンまたはテオブロミンである前記(1)〜(8)のいずれかに記載の予防、改善または治療組成物、
(10)イソフラボン類が、大豆イソフラボンである前記(1)〜(9)のいずれかに記載の予防、改善または治療組成物、
(11)大豆イソフラボンが、ゲニステイン、ダイゼイン、グリシテイン、ゲニスチン、ダイジンまたはグリシチンである前記(10)に記載の予防、改善または治療組成物、
(12)カルニチン類が、L−カルニチン、N−アセチル−L−カルニチン、またはそれらの医薬もしくは食品として許容される塩である前記(1)〜(11)のいずれかに記載の予防、改善または治療組成物、
(13)カルニチン前駆体が、リジンまたはそれらの医薬もしくは食品として許容される塩、およびメチオニンである前記(1)〜(12)のいずれかに記載の予防、改善または治療組成物、
(14)アルギニン、カフェイン、イソフラボン類およびカルニチンを含有する前記(1)〜(7)のいずれかに記載の予防、改善または治療組成物、
(15)前記(1)〜(14)のいずれかに記載の予防、改善または治療組成物を含有してなる飲食品または医薬品、および
(16)グルカゴン分泌亢進作用を有するアミノ酸類の少なくとも1種、キサンチン誘導体の少なくとも1種、イソフラボン類の少なくとも1種、およびカルニチン類もしくはカルニチン前駆体の少なくとも1種を含有してなる組成物を含有する飲食品であって、脂質代謝を改善する旨の表示、基礎代謝を促進する旨の表示、体重を減少させる旨の表示、内臓脂肪または皮下脂肪を減少させる旨の表示、ダイエット効果を有する旨の表示、脂肪肝および/または肝機能を改善する旨の表示、血中中性脂肪濃度を減少させる旨の表示、血中総コレステロール濃度を減少させる旨の表示、血中HDLコレステロール濃度を増加させる旨の表示、血中アディポネクチン濃度を増加させる旨の表示、アディポサイトカインの分泌を正常化する作用を有する旨の表示、肥満の予防、治療もしくは症状の改善に用いることができる旨の表示、メタボリックシンドロームの予防、治療もしくは症状の改善に用いることができる旨の表示、からなる群から選択される少なくとも1種の表示が付されたものである飲食品、
に関する。
That is, the present invention comprises (1) at least one amino acid having a glucagon secretion enhancing action, at least one xanthine derivative, at least one isoflavone, and at least one carnitine or carnitine precursor. Metabolic syndrome prevention, amelioration or treatment composition,
(2) A lipid metabolism abnormality comprising at least one amino acid having an action of enhancing glucagon secretion, at least one xanthine derivative, at least one isoflavone, and at least one carnitine or carnitine precursor. Preventive, ameliorating or therapeutic compositions,
(3) The composition for preventing, improving or treating lipid metabolism abnormality according to the above (2), wherein the lipid metabolism abnormality is fatty liver,
(4) The composition for preventing, improving or treating lipid metabolism abnormality according to the above (2), wherein the lipid metabolism abnormality is hypercholesterolemia,
(5) The composition for preventing, improving or treating lipid metabolism abnormality according to the above (2), wherein the lipid metabolism abnormality is hypertriglyceridemia,
(6) Prevention of obesity comprising at least one amino acid having a glucagon secretion enhancing action, at least one xanthine derivative, at least one isoflavone, and at least one carnitine or carnitine precursor, Improvement or treatment composition,
(7) A composition for preventing, improving or treating obesity according to the above (6), wherein obesity is caused by visceral fat and / or subcutaneous fat,
(8) The prevention, improvement, or treatment according to any one of (1) to (7) above, wherein the amino acids having a glucagon secretion enhancing action are arginine, alanine, leucine, or a salt acceptable as a pharmaceutical or food thereof. Composition,
(9) The preventive, ameliorating or therapeutic composition according to any one of (1) to (8), wherein the xanthine derivative is caffeine, theophylline or theobromine,
(10) The preventive, ameliorating or therapeutic composition according to any one of (1) to (9), wherein the isoflavones are soybean isoflavones,
(11) The preventive, ameliorating or therapeutic composition according to the above (10), wherein the soybean isoflavone is genistein, daidzein, glycitein, genistin, daidzin or glycitin,
(12) Prevention, improvement, or improvement according to any one of (1) to (11) above, wherein the carnitines are L-carnitine, N-acetyl-L-carnitine, or a pharmaceutically or food acceptable salt thereof. Therapeutic composition,
(13) The preventive, ameliorating or therapeutic composition according to any one of (1) to (12), wherein the carnitine precursor is lysine or a pharmaceutically or food acceptable salt thereof, and methionine.
(14) The preventive, ameliorating or therapeutic composition according to any one of (1) to (7), comprising arginine, caffeine, isoflavones and carnitine,
(15) At least one of foods and beverages or pharmaceuticals containing the preventive, ameliorating or therapeutic composition according to any one of (1) to (14), and (16) amino acids having a glucagon secretion enhancing action , A food and drink containing a composition comprising at least one xanthine derivative, at least one isoflavone, and at least one carnitine or carnitine precursor, wherein the lipid metabolism is improved Indications to promote basal metabolism, indications to reduce body weight, indications to reduce visceral fat or subcutaneous fat, indications to have a diet effect, indications to improve fatty liver and / or liver function Display, indication to reduce blood triglyceride concentration, indication to reduce blood total cholesterol concentration, blood HDL cholesterol concentration An indication to increase the blood adiponectin concentration, an indication to have the effect of normalizing the secretion of adipocytokine, an indication that it can be used to prevent obesity, treat or improve symptoms, A food and drink with at least one indication selected from the group consisting of indications that can be used for prevention, treatment or improvement of symptoms of metabolic syndrome,
About.
本発明の組成物は、脂肪肝、高脂血症(例えば、高中性脂肪血症、高コレステロール血症)などの脂質代謝異常や、内臓脂肪や皮下脂肪に起因する肥満を予防、改善、治療することができると共に、これらの症状を伴うメタボリックシンドロームを予防、改善または治療することができる。 The composition of the present invention prevents, improves, and treats lipid metabolism abnormalities such as fatty liver and hyperlipidemia (for example, hypertriglyceremia, hypercholesterolemia) and obesity caused by visceral fat and subcutaneous fat. And metabolic syndrome associated with these symptoms can be prevented, ameliorated, or treated.
本発明の組成物は、グルカゴン分泌亢進作用を有するアミノ酸類の少なくとも1種、キサンチン誘導体の少なくとも1種、イソフラボン類の少なくとも1種、およびカルニチン類もしくはカルニチン前駆体の少なくとも1種を含有してなることを特徴とする。 The composition of the present invention comprises at least one amino acid having a glucagon secretion enhancing action, at least one xanthine derivative, at least one isoflavone, and at least one carnitine or carnitine precursor. It is characterized by that.
本発明の組成物の第1の成分である“グルカゴン分泌亢進作用を有するアミノ酸類”としては、例えば、アルギニン、アラニン、ロイシンなどが挙げられ、なかでもアルギニンが最も好ましい。これらのアミノ酸は、遊離のアミノ酸でもよいし、生理学的に許容される塩(すなわち、医薬品または飲食品として許容される塩)の形態でもよい。塩としては、例えば、ナトリウム塩、カルシウム塩などの金属塩、塩酸塩、炭酸塩、硫酸塩などの無機酸塩、酢酸塩、リンゴ酸塩、コハク酸塩などの有機酸塩などが挙げられる。本発明の組成物は、上記したグルカゴン分泌亢進作用を有するアミノ酸類を1種または2種以上(例、2種または3種)含んでいてもよい。 Examples of the “amino acids having a glucagon secretion enhancing action” as the first component of the composition of the present invention include arginine, alanine, leucine and the like, and arginine is most preferable. These amino acids may be free amino acids or may be in the form of physiologically acceptable salts (that is, salts acceptable as pharmaceuticals or foods and drinks). Examples of the salt include metal salts such as sodium salt and calcium salt, inorganic acid salts such as hydrochloride, carbonate and sulfate, and organic acid salts such as acetate, malate and succinate. The composition of the present invention may contain one or more amino acids (eg, two or three) having the above-described action for enhancing glucagon secretion.
本発明の組成物の第2の成分である“キサンチン誘導体”としては、天然由来のキサンチン誘導体がより好ましく、具体的にはカフェイン、テオフィリン、テオブロミンなどが挙げられる。なかでもカフェインが最も好ましい。 The “xanthine derivative” as the second component of the composition of the present invention is more preferably a xanthine derivative derived from nature, and specifically caffeine, theophylline, theobromine and the like. Of these, caffeine is most preferable.
本発明の組成物の第3の成分である“イソフラボン類”としては、大豆イソフラボンなどが挙げられ、大豆イソフラボンとしては、ゲニステイン、ダイゼインまたはグリシテインの非配糖体であってもよく、ゲニスチン、ダイジンまたはグリシチンの配糖体であってもよいが、なかでもゲニステインが最も好ましい。また、本発明の組成物は、これらを1種または2種以上(例、2種または3種)含んでいてもよい。 Examples of the “isoflavones” as the third component of the composition of the present invention include soy isoflavones, and the soy isoflavones may be non-glycosides of genistein, daidzein, or glycitein, genistin, daidzin Alternatively, a glycoside of glycitin may be used, but genistein is most preferable. Moreover, the composition of this invention may contain these 1 type, or 2 or more types (for example, 2 types or 3 types).
本発明の組成物の第4の成分である“カルニチン類もしくはカルニチン前駆体”におけるカルニチン類としては、L−カルニチン、N−アセチル−L−カルニチン、DL−カルニチン、塩化カルニチン(=DL−カルニチン塩酸塩)、L−カルニチン塩酸塩、L−カルニチンフマル酸塩、L−カルニチン酒石酸塩、L−カルニチンマグネシウムクエン酸塩、N−アセチル−L−カルニチン塩酸塩などが挙げられる。その中でも、L−カルニチン、N−アセチル−L−カルニチン、L−カルニチンの塩が好ましく、特に好ましいものとしては、L−カルニチン、N−アセチル−L−カルニチン、L−カルニチン塩酸塩、L−カルニチンフマル酸塩、L−カルニチン酒石酸塩が挙げられる。 Examples of carnitines in the “carnitines or carnitine precursors” as the fourth component of the composition of the present invention include L-carnitine, N-acetyl-L-carnitine, DL-carnitine, carnitine chloride (= DL-carnitine hydrochloride). Salt), L-carnitine hydrochloride, L-carnitine fumarate, L-carnitine tartrate, L-carnitine magnesium citrate, N-acetyl-L-carnitine hydrochloride and the like. Of these, salts of L-carnitine, N-acetyl-L-carnitine, and L-carnitine are preferable, and particularly preferable examples include L-carnitine, N-acetyl-L-carnitine, L-carnitine hydrochloride, and L-carnitine fumarate. Acid salt and L-carnitine tartrate.
本発明の組成物の第4の成分である“カルニチン類もしくはカルニチン前駆体”におけるカルニチン前駆体としては、リジンまたはその医薬もしくは食品として許容される塩、およびメチオニンなどが挙げられる。 Examples of the carnitine precursor in the “carnitines or carnitine precursor” as the fourth component of the composition of the present invention include lysine or a pharmaceutically or food acceptable salt thereof, methionine, and the like.
本発明の組成物の成分の組み合わせとして、特にアルギニン、カフェイン、イソフラボン類の少なくとも1種、およびカルニチンの組み合わせが好ましい。 The combination of the components of the composition of the present invention is particularly preferably a combination of arginine, caffeine, at least one of isoflavones, and carnitine.
上記“グルカゴン分泌亢進作用を有するアミノ酸類”に対する“キサンチン誘導体”、“イソフラボン類”および“カルニチン類もしくはカルニチン前駆体”(カルニチン類とカルニチン前駆体の両方を用いるときはその合計)の配合比(重量比)としては、それぞれ通常1:約0.01〜5:約0.005〜5:約0.01〜50、好ましくは1:約0.02〜1:約0.01〜1:約0.02〜10、最も好ましくは1:約0.05〜0.5:約0.02〜0.5:約0.03〜5である。 Mixing ratio of “xanthine derivatives”, “isoflavones” and “carnitines or carnitine precursors” (the total when using both carnitines and carnitine precursors) to the above “amino acids having a glucagon secretion enhancing action” ( The weight ratio is usually about 1: about 0.01 to 5: about 0.005 to 5: about 0.01 to 50, preferably about 1: about 0.02 to about 0.01 to about 1: 0.02 to 10, most preferably 1: about 0.05 to 0.5: about 0.02 to 0.5: about 0.03 to 5.
本発明の組成物は更に所望に応じて飲食品、医薬品として許容される各種の担体および/または添加剤を添加配合することができる。このような担体の例としては、各種のキャリアー担体、イクステンダー剤、希釈剤、増量剤、分散剤、賦形剤、結合剤、溶媒(例えば、水、エタノール、植物油など)、溶解補助剤、緩衝剤、溶解促進剤、ゲル化剤(例えば、ナトリウムCMC、HPMCなど)、懸濁化剤(例えば、ナトリウムCMC、ナトリウムアルギネートなど)などが挙げられ、添加剤の例としては、ビタミン類(例えば、ビタミンA、ビタミンB1、ビタミンB2、ビタミンB6、パントテン酸、ニコチン酸、ビタミンC、ビタミンEなど)、甘味料、有機酸(例えば、クエン酸、リンゴ酸、フマル酸、マロン酸、コハク酸、酒石酸、乳酸など)、着色剤、香料(例えば、バニリン、リナロール、天然香料など)、湿気防止剤、ファイバー、電解質、ミネラル、栄養素、抗酸化剤、保存剤、芳香剤、湿潤剤、天然の植物抽出物(例えば、茶抽出物、コーヒー抽出物、ココア抽出物、オレンジ、グレープ、アップル、モモ、パイナップル、ナシ、プラム、サクランボ、パパイヤ、トマト、メロン、イチゴ、ラズベリーなどのフルーツ抽出物など)などが挙げられる。 The composition of the present invention may further contain various carriers and / or additives acceptable as foods and beverages and pharmaceuticals as desired. Examples of such carriers include various carrier carriers, extender agents, diluents, extenders, dispersants, excipients, binders, solvents (eg, water, ethanol, vegetable oils, etc.), solubilizers, Buffering agents, dissolution promoters, gelling agents (for example, sodium CMC, HPMC, etc.), suspending agents (for example, sodium CMC, sodium alginate, etc.) and the like, and examples of additives include vitamins (for example, , Vitamin A, vitamin B1, vitamin B2, vitamin B6, pantothenic acid, nicotinic acid, vitamin C, vitamin E, etc.), sweeteners, organic acids (eg, citric acid, malic acid, fumaric acid, malonic acid, succinic acid, Tartaric acid, lactic acid, etc.), coloring agents, fragrances (eg, vanillin, linalool, natural fragrances, etc.), moisture inhibitors, fibers, electrolytes, minerals, nutrition , Antioxidants, preservatives, fragrances, wetting agents, natural plant extracts (e.g. tea extract, coffee extract, cocoa extract, orange, grape, apple, peach, pineapple, pear, plum, cherry, Papaya, tomato, melon, strawberry, raspberry and other fruit extracts).
本発明の組成物は、飲食品、医薬品に適した各種の形態に調製することができる。飲食品としては、例えばダイエット食品、缶詰食品、ジュース、シロップなどを含めた飲食品製造に通常用いられる方法で調合したり、製造したりすることができる。例えば飲料は、本発明組成物の必須成分および所望に応じて上記の添加剤の所定量を適当な希釈剤(通常は水)に溶解して調製される。飲料全量に対する必須成分の配合量は特に制限はないが、全量100gあたり必須成分の配合量は0.01〜15g、好ましくは0.05〜10g、最も好ましくは0.1〜4gである。また、本発明の飲料は炭酸飲料の形態に調製してもよい。本発明の飲料は、飲む直前にすぐに調製しうるに適した粉末形態のものであってもよい。非飲料食品形態としては例えば、アメ、ドロップ、チョコレート、ゼリー、ビスケット、ヨーグルトおよび菓子などの各種の形態をとることができる。これらの非飲料食品形態への調製は、本発明の必須成分および所望に応じて上記の添加剤の所定量を適宜混合して賦形するか、またはさらに適当な担体を適宜混合して賦形することにより行われる。 The composition of the present invention can be prepared in various forms suitable for foods and drinks and pharmaceuticals. As food / beverage products, for example, they can be prepared or produced by methods usually used for the production of food / beverage products including diet foods, canned foods, juices, syrups and the like. For example, a beverage is prepared by dissolving the essential components of the composition of the present invention and, if desired, a predetermined amount of the above-described additive in an appropriate diluent (usually water). Although the compounding quantity of the essential component with respect to the whole quantity of beverages is not particularly limited, the compounding quantity of the essential ingredient per 0.01 g of the total quantity is 0.01 to 15 g, preferably 0.05 to 10 g, and most preferably 0.1 to 4 g. Moreover, you may prepare the drink of this invention in the form of a carbonated drink. The beverage of the present invention may be in the form of a powder suitable for being ready to be prepared immediately before drinking. Non-drinking food forms can take various forms such as candy, drop, chocolate, jelly, biscuits, yogurt and confectionery. These non-beverage food forms are prepared by appropriately mixing the essential ingredients of the present invention and a predetermined amount of the above-mentioned additives as desired, or by further appropriately mixing an appropriate carrier. Is done.
担体としては例えば、小麦粉、米粉、澱粉、コーンスターチ、ポリサッカライド、ミルクタンパク質、コラーゲン、米油、レシチンなどが挙げられる。非飲料食品全量に対する必須成分と添加剤の配合量は特に制限はないが、全量100gあたり必須成分の配合量は0.01〜20g、好ましくは0.05〜10g、最も好ましくは0.1〜4gである。医薬品としては錠剤、カプセル剤、液剤、散剤、注射剤などの中から常法に従って任意の剤形に製剤化することができる。成人1日あたりの投与量は、経口投与の場合、アミノ酸が100mg以上、好ましくは200mg〜20g、特に好ましくは300mg〜5g、キサンチン誘導体が通常1〜200mg、好ましくは5〜100mg、特に好ましくは20〜80mg程度、イソフラボン類が1mg以上、好ましくは10〜100mg、特に好ましくは25〜40mg程度、カルニチン類もしくはカルニチン前駆体(カルニチン類とカルニチン前駆体の両方を用いるときはその合計)が通常10mg〜2g、好ましくは30mg〜1g、特に好ましくは50mg〜500mgである。 Examples of the carrier include wheat flour, rice flour, starch, corn starch, polysaccharide, milk protein, collagen, rice oil, lecithin and the like. The blending amount of the essential ingredients and additives with respect to the total amount of the non-drinking food is not particularly limited, but the blending quantity of the essential ingredients per 100 g of the total amount is 0.01 to 20 g, preferably 0.05 to 10 g, most preferably 0.1 to 0.1 g. 4g. As a pharmaceutical, it can be formulated into any dosage form from tablets, capsules, liquids, powders, injections and the like according to a conventional method. In the case of oral administration, the daily dose for an adult is 100 mg or more, preferably 200 mg to 20 g, particularly preferably 300 mg to 5 g, and the xanthine derivative is usually 1 to 200 mg, preferably 5 to 100 mg, particularly preferably 20 mg. About 80 mg, isoflavones 1 mg or more, preferably 10-100 mg, particularly preferably about 25-40 mg, carnitine or carnitine precursor (the total when using both carnitine and carnitine precursor) is usually 10 mg- The amount is 2 g, preferably 30 mg to 1 g, particularly preferably 50 mg to 500 mg.
本発明の組成物を飲食品の形態に調製した場合、該飲食品には、当該組成物の作用に鑑みて、脂質代謝を改善する旨の表示、基礎代謝を促進する旨の表示、体重を減少させる旨の表示、内臓脂肪または皮下脂肪を減少させる旨の表示、ダイエット効果を有する旨の表示、脂肪肝および/または肝機能を改善する旨の表示、血中中性脂肪濃度を減少させる旨の表示、血中総コレステロール濃度を減少させる旨の表示、血中HDLコレステロール濃度を増加させる旨の表示、血中アディポネクチン濃度を増加させる旨の表示、アディポサイトカインの分泌を正常化する作用を有する旨の表示、肥満の予防、治療もしくは症状の改善に用いることができる旨の表示、および/またはメタボリックシンドロームの予防、治療もしくは症状の改善に用いることができる旨の表示をすることができる。 When the composition of the present invention is prepared in the form of a food or drink, the food or drink has an indication of improving lipid metabolism, an indication of promoting basal metabolism, and weight in view of the action of the composition. An indication to reduce, an indication to reduce visceral fat or subcutaneous fat, an indication to have a diet effect, an indication to improve fatty liver and / or liver function, an effect to reduce blood neutral fat concentration Indication of reducing blood total cholesterol concentration, indication of increasing blood HDL cholesterol concentration, indication of increasing blood adiponectin concentration, effect of normalizing adipocytokine secretion Used to prevent, treat or improve symptoms of metabolic syndrome, and / or to indicate that it can be used to prevent or treat obesity It can be an indication that it is possible.
以下に実施例および試験例をあげて本発明をさらに具体的に説明するが、本発明はこれらに限定されるものではない。なお、以下の実施例および試験例において、イソフラボン類は用途に応じて成分や組成比が異なる数種の食品素材を用いた。そのような食品素材として、例えば、大豆イソフラボンアグリコンであるゲニステイン、ダイゼインおよびグリシテインの混合物や大豆イソフラボン配糖体であるゲニスチン、ダイジンおよびグリシチンの混合物が挙げられる。また、以下の実施例および試験例において、カルニチンおよびアルギニンはL−体を用いた。 The present invention will be described more specifically with reference to the following examples and test examples, but the present invention is not limited to these examples. In the following Examples and Test Examples, several kinds of food materials having different components and composition ratios were used as isoflavones depending on applications. Examples of such food materials include a mixture of genistein, daidzein and glycitein, which are soy isoflavone aglycones, and a mixture of genistin, daidzin and glycitin, which are soy isoflavone glycosides. In the following Examples and Test Examples, L-forms were used for carnitine and arginine.
[実施例1]
(散剤)
イソフラボン類(大豆イソフラボンを30重量%以上含有する大豆発酵抽出物であって、該大豆イソフラボンの組成比がゲニステイン約50重量%、ダイゼイン約40重量%、グリシテイン約10重量%である食品素材)0.015g、カルニチン0.1g、アルギニン0.5g、カフェイン0.02g、ビタミンC0.015g、合成ケイ酸アルミニウム10g、リン酸水素カリウム5g、乳糖84.5g、これら粉末状の成分を均一に混合して、散剤とする。
[Example 1]
(Powder)
Isoflavones (a soy fermented extract containing 30% by weight or more of soybean isoflavone, a food material having a composition ratio of soy isoflavone of about 50% by weight of genistein, about 40% by weight of daidzein, and about 10% by weight of glycitein) .015 g, carnitine 0.1 g, arginine 0.5 g, caffeine 0.02 g, vitamin C 0.015 g, synthetic aluminum silicate 10 g, potassium hydrogen phosphate 5 g, lactose 84.5 g, and these powdered ingredients are mixed uniformly And powder.
[実施例2]
(顆粒剤)
イソフラボン類(大豆イソフラボンを30重量%以上含有する大豆発酵抽出物であって、該大豆イソフラボンの組成比がゲニステイン約50重量%、ダイゼイン約40重量%、グリシテイン約10重量%である食品素材)0.015g、カルニチン0.1g、アルギニン0.5g、カフェイン0.02g、ビタミンC0.015g、結晶セルロース40.0g、乳糖35.0g、澱粉19.5g、ポリビニルアルコール5.0g、水30.0g、これらの上記成分を均一に混練し、破砕造粒した後、乾燥して顆粒剤とする。
[Example 2]
(Granule)
Isoflavones (a soy fermented extract containing 30% by weight or more of soybean isoflavone, a food material having a composition ratio of soy isoflavone of about 50% by weight of genistein, about 40% by weight of daidzein, and about 10% by weight of glycitein) .015 g, carnitine 0.1 g, arginine 0.5 g, caffeine 0.02 g, vitamin C 0.015 g, crystalline cellulose 40.0 g, lactose 35.0 g, starch 19.5 g, polyvinyl alcohol 5.0 g, water 30.0 g These components are uniformly kneaded, crushed and granulated, and then dried to form granules.
[実施例3]
(錠剤)
実施例2で得られた顆粒剤99gにステアリン酸カルシウム1gを混合し、打錠機で圧縮成形して直径6.0mmの錠剤とする。
[Example 3]
(tablet)
1 g of calcium stearate is mixed with 99 g of the granule obtained in Example 2, and compressed into a tablet having a diameter of 6.0 mm with a tableting machine.
[実施例4]
(配合茶)
緑茶、ハト麦、大麦、玄米、ウーロン茶、ドクダミおよび杜仲茶の7種類を原料とする乾燥茶葉1gを100mlの水で抽出し、この抽出液にイソフラボン類(大豆イソフラボンを10重量%含有する大豆胚芽抽出物であって、該大豆イソフラボンの組成比がゲニスチン約10重量%、ダイジン約50重量%、グリシチン約40重量%である食品素材)8mg、カルニチン60mg、アルギニン240mg、カフェイン10mg、およびビタミンC 15mgを配合し、配合茶を得た。(原料由来のカフェインが2mg入っている。)
[Example 4]
(Mixed tea)
1 g of dried tea leaves made from seven kinds of green tea, pigeons, barley, brown rice, oolong tea, dokudami and tochu tea are extracted with 100 ml of water, and isoflavones (soy germ containing 10% by weight of soy isoflavones) are extracted into this extract. A food material in which the composition ratio of the soy isoflavone is about 10% by weight of genistin, about 50% by weight of daidin, and about 40% by weight of glycine) 8 mg, carnitine 60 mg, arginine 240 mg,
[実施例5]
(粉末茶)
玄米茶エキス1800mg、乳糖500mg、クエン酸500mg、イソフラボン類(大豆イソフラボンを10重量%含有する大豆胚芽抽出物であって、該大豆イソフラボンの組成比がゲニスチン約10重量%、ダイジン約50重量%、グリシチン約40重量%である食品素材)40mg、カルニチン300mg、アルギニン1300mgおよびカフェイン55mgを配合し、粉末茶を得た。(原料由来のカフェインが20mg入っている。)
[Example 5]
(Powdered tea)
Brown rice tea extract 1800 mg, lactose 500 mg, citric acid 500 mg, isoflavones (a soy germ extract containing 10% by weight of soy isoflavone, the composition ratio of soy isoflavone is about 10% by weight of genistin, about 50% by weight of daidzin, 40 mg of a glycitin food material) 40 mg, carnitine 300 mg, arginine 1300 mg and caffeine 55 mg were blended to obtain a powdered tea. (Contains 20 mg of caffeine derived from raw materials.)
[実施例6]
(キャンディー)
イソフラボン類(大豆イソフラボンを10重量%含有する大豆胚芽抽出物であって、該大豆イソフラボンの組成比がゲニスチン約10重量%、ダイジン約50重量%、グリシチン約40重量%である食品素材)15mg、カルニチン100mg、アルギニン400mg、カフェイン20mg、クエン酸100mg、ビタミンC15mg、水飴65g、蔗糖10g、マレイン酸300mg、コハク酸200mg、リンゴ酸150mg、香料0.3gおよび水少量を混合し、常法により加熱冷却し、キャンディーを製造した。
[Example 6]
(Candy)
15 mg of isoflavones (a soy germ extract containing 10% by weight of soy isoflavone, the composition of the soy isoflavone is about 10% by weight of genistin, about 50% by weight of daidin, and about 40% by weight of glycitin),
以下の試験例で用いたマウスは、2型糖尿病モデル動物のKKマウスである。KKマウスは遺伝性糖尿病動物であるが、自然に糖尿病を発症するわけではなく、食餌を主とした飼育条件の規制が必要である。すなわち、市販の固型飼料で飼育しても高血糖は発症しにくいが、高カロリー飼料で飼育すると容易に食餌性肥満を起こし高血糖を発症する。さらに、食餌性肥満および高血糖を発症したKKマウスをそのまま高カロリー飼料で飼育すると体重の増加、高血糖、高インスリン血症および高コレステロール血症がみられ、肝臓中性脂肪量の増加(脂肪肝)と皮下脂肪や内臓脂肪の組織重量が増加して病態が悪化する。このように、KKマウスはヒト肥満の成因や病態をよく反映したモデル動物であり、内臓脂肪蓄積に伴うインスリン抵抗性、さらには高血糖、高インスリン血症、高脂血症、高コレステロール血症など、メタボリックシンドロームのモデル動物として用いることができる。
また、以下の試験例に用いたイソフラボン類は、食品素材の大豆イソフラボン(大豆イソフラボンを10重量%含有する大豆胚芽抽出物であって、該大豆イソフラボンの組成比がゲニスチン約10重量%、ダイジン約50重量%、グリシチン約40重量%である食品素材)である。
The mice used in the following test examples are
In addition, the isoflavones used in the following test examples are soy isoflavones of food materials (a soy germ extract containing 10% by weight of soy isoflavones, the composition ratio of soy isoflavones is about 10% by weight of genistin, about about daidzin 50% by weight and about 40% by weight glycitin food material).
[試験例1]
本発明のイソフラボン類、カルニチン、アルギニンおよびカフェインを含有する組成物の肝臓における中性脂肪合成抑制作用を、肝臓における中性脂肪の合成が亢進する絶食−再給餌評価系で調べた。
16−20週齢の雄性KKマウスを使用し、2日間絶食させた後、4群(対照群、アルギニン・カフェイン混合物投与群、イソフラボン類・カルニチン混合物投与群、およびイソフラボン類・カルニチン・アルギニン・カフェインの組成物(本発明品)投与群、1群6匹)に分けた。下記表1に示す組成からなる高炭水化物飼料を摂取させた群を対照群とし、高炭水化物食に試験サンプルを加えたものを摂取させた群を試験群として3日間再給餌した。各試験群の飼料は次のとおりである。
(1)対照群:高炭水化物飼料
(2)アルギニン・カフェイン混合物投与群:高炭水化物飼料+(アルギニン0.6重量%+カフェイン0.025重量%の混合物)
(3)イソフラボン類・カルニチン混合物投与群:高炭水化物飼料+(大豆イソフラボン0.02重量%+カルニチン0.15重量%の混合物)
(4)本発明品投与群:高炭水化物飼料+(大豆イソフラボン0.02重量%+カルニチン0.15重量%+アルギニン0.6重量%+カフェイン0.025重量%の混合物)。
[Test Example 1]
The effect of the composition containing the isoflavones, carnitine, arginine and caffeine of the present invention on the neutral fat synthesis in the liver was examined in a fasting-refeeding evaluation system in which the synthesis of neutral fat in the liver was enhanced.
After using male KK mice of 16-20 weeks of age and fasting for 2 days, 4 groups (control group, arginine / caffeine mixture administration group, isoflavone / carnitine mixture administration group, and isoflavone / carnitine / arginine / The composition was divided into a caffeine composition (product of the present invention) administration group, 6 mice per group). A group fed with a high carbohydrate feed comprising the composition shown in Table 1 below was used as a control group, and a group fed with a high carbohydrate diet plus a test sample was fed as a test group for 3 days. The feed of each test group is as follows.
(1) Control group: High carbohydrate feed (2) Arginine / caffeine mixture administration group: High carbohydrate feed + (mixture of arginine 0.6 wt% + caffeine 0.025 wt%)
(3) isoflavones-carnitine mixture treated group: (mixture of soy isoflavones 0.02 wt% + carnitine 0.15 wt%) high carbohydrate diet +
(4) Invention product administration group: High carbohydrate feed + (mixture of soybean isoflavone 0.02 wt% + carnitine 0.15 wt% + arginine 0.6 wt% + caffeine 0.025 wt%).
飼育試験終了後、解剖して各群マウスの肝臓組織の重量を測定し、また肝臓の中性脂肪濃度を常法により分析した。その結果を図1に示す。なお、図1では中性脂肪濃度(mg/g肝臓)を平均値±標準偏差で示した。p<0.01は危険率1%未満で対照群と有意な差があることを意味する。 After completion of the breeding test, the mice were dissected and the liver tissue weight of each group of mice was measured, and the neutral fat concentration of the liver was analyzed by a conventional method. The result is shown in FIG. In FIG. 1, the neutral fat concentration (mg / g liver) is shown as an average value ± standard deviation. p <0.01 means that there is a significant difference from the control group at a risk rate of less than 1%.
図1から次のことが分かる。すなわち、対照群では肝臓での中性脂肪の合成が亢進し、中性脂肪濃度が増加しているのに対し、アルギニン・カフェイン混合物投与群および本発明品投与群では、中性脂肪濃度は増加が抑えられており、対照群と比べて有意(p<0.01)に低値を示した。一方、イソフラボン類・カルニチン混合物投与群は対照群と比較して差はみられなかった。また、イソフラボン類・カルニチン・アルギニン・カフェイン組成物(本発明品)投与群はアルギニン・カフェイン混合物投与群と同程度の値を示しており、イソフラボン類・カルニチン混合物摂取による脂肪合成抑制作用はみられなかった。イソフラボン類は脂肪分解を促進させることおよび脂肪酸酸化酵素カルニチンパルミトイルトランスフェラーゼ1を活性化することにより、また、カルニチンはエネルギー代謝に関与することにより抗肥満作用を示す。そのため、絶食−再給餌による一過性の脂肪合成においてはイソフラボン類・カルニチン混合物摂取による効果がみられなかったと考えられる。 The following can be seen from FIG. That is, in the control group, the synthesis of neutral fat in the liver is increased and the neutral fat concentration is increased, whereas in the arginine / caffeine mixture administration group and the present invention product administration group, the neutral fat concentration is The increase was suppressed and the value was significantly lower (p <0.01) than the control group. On the other hand, there was no difference in the isoflavones / carnitine mixture administration group compared to the control group. In addition, the isoflavones / carnitine / arginine / caffeine composition (invention product) administration group showed the same value as the arginine / caffeine mixture administration group. It was not seen. Isoflavones exhibit anti-obesity action by promoting lipolysis and activating the fatty acid oxidase carnitine palmitoyltransferase 1, and carnitine is involved in energy metabolism. Therefore, it is considered that the effect of ingesting the isoflavones / carnitine mixture was not observed in the transient fat synthesis by fasting-refeeding.
[試験例2]
食餌性肥満マウスのカロリー摂取を制限し、体脂肪の分解・利用を必要とする状態にすると、体脂肪の分解・利用の促進が肥満を改善する。このような条件下で、本発明のイソフラボン類、カルニチン、アルギニンおよびカフェインを含有する組成物の作用を調べた。すなわち、5週齢の雄性KKマウスを、水と飼育用粉末飼料(CE−2、商品名、日本クレア株式会社製)で1週間飼育した後、下記表2に記載の高カロリー飼料(4.66kcal/g)で3週間飼育して肥満を誘導した。4群(対照群、アルギニン・カフェイン混合物投与群、イソフラボン類・カルニチン混合物投与群、およびイソフラボン類・カルニチン・アルギニン・カフェインの組成物(本発明品)投与群、1群6匹)に分け、下記表2に記載の低カロリー飼料(3.08kcal/g)、あるいは、低カロリー飼料に試験サンプルを加えた飼料で2週間飼育して体脂肪を利用させた。各試験群の飼料は次のとおりである。
(1)対照群:低カロリー飼料
(2)アルギニン・カフェイン混合物投与群:低カロリー飼料+(アルギニン0.6重量%+カフェイン0.025重量%の混合物)
(3)イソフラボン類・カルニチン混合物投与群:低カロリー飼料+(大豆イソフラボン0.02重量%+カルニチン0.15重量%の混合物)
(4)本発明品投与群:低カロリー飼料+(大豆イソフラボン0.02重量%+カルニチン0.15重量%+アルギニン0.6重量%+カフェイン0.025重量%の混合物)。
[Test Example 2]
When dietary obese mice limit caloric intake and require body fat degradation / utilization, the promotion of body fat degradation / utilization improves obesity. Under such conditions, the action of the composition containing the isoflavones of the present invention, carnitine, arginine and caffeine was examined. That is, a 5-week-old male KK mouse was bred for 1 week with water and a powdered feed for breeding (CE-2, trade name, manufactured by Clea Japan Co., Ltd.), and then the high-calorie diet described in Table 2 below (4. 66 kcal / g) for 3 weeks to induce obesity. Divided into 4 groups (control group, arginine / caffeine mixture administration group, isoflavone / carnitine mixture administration group, isoflavone / carnitine / arginine / caffeine composition (invention product) administration group, 6 per group) The low-calorie diet (3.08 kcal / g) described in Table 2 below, or a diet obtained by adding a test sample to a low-calorie diet, was bred for 2 weeks to use body fat. The feed of each test group is as follows.
(1) Control group: low-calorie diet (2) Arginine / caffeine mixture administration group: low-calorie diet + (mixture of arginine 0.6 wt% + caffeine 0.025 wt%)
(3) Isoflavone / carnitine mixture administration group: low-calorie diet + (mixture of soybean isoflavone 0.02 wt% + carnitine 0.15 wt%)
(4) Invention product administration group: low calorie feed + (mixture of soybean isoflavone 0.02 wt% + carnitine 0.15 wt% + arginine 0.6 wt% + caffeine 0.025 wt%).
試験期間中は体重測定を定期的に実施し、試験終了後に解剖して各群マウスの皮下および腸間膜周囲(内臓)脂肪組織重量を測定した。また、試験サンプル投与前および試験終了後に採血を行い、血漿中脂質含量を常法により分析した。また、試験終了後に肝臓を摘出して、肝臓中の脂質含量を常法により分析した。 During the test period, body weight measurement was performed periodically, and after the test was completed, the mice were dissected and the weight of the subcutaneous and peri-mesenteric (visceral) adipose tissue of each group of mice was measured. In addition, blood was collected before administration of the test sample and after completion of the test, and plasma lipid content was analyzed by a conventional method. Moreover, the liver was extracted after completion | finish of a test, and the lipid content in a liver was analyzed by the conventional method.
結果を図2〜図7に示す。これらの図中、体重の増減量(g)、皮下脂肪組織重量(mg/100g体重)、腸間膜周囲(内臓)脂肪組織重量(mg/100g体重)、血漿中性脂肪量(mg/dl)、血漿総コレステロール量(mg/dl)、および肝臓中性脂肪量(mg/g肝臓)は平均値±標準偏差で示した。また、p<0.01およびp<0.05は、それぞれ危険率1%未満および5%未満で対照群と有意な差があることを示す。 The results are shown in FIGS. In these figures, the amount of increase / decrease in body weight (g), subcutaneous fat tissue weight (mg / 100 g body weight), peri-mesenteric (visceral) adipose tissue weight (mg / 100 g body weight), plasma neutral fat amount (mg / dl) ), Plasma total cholesterol level (mg / dl), and liver triglyceride level (mg / g liver) are shown as mean ± standard deviation. Moreover, p <0.01 and p <0.05 indicate that there is a significant difference from the control group at a risk rate of less than 1% and less than 5%, respectively.
これらの結果から次のことが分かる。すなわち、体重の増減量および肝臓中性脂肪量は、対照群と比較してイソフラボン類・カルニチン混合物投与群とアルギニン・カフェイン混合物投与群は大差ないが、本発明品投与群が有意に低値を示し、明確な相乗作用がみられた。また、皮下脂肪および腸間膜周囲(内臓)脂肪組織重量は、対照群と比較してイソフラボン類・カルニチン混合物投与群は大差なく、アルギニン・カフェイン混合物投与群は低値を示したが有意差はなかった。一方、本発明品投与群は有意に低値を示し、明確な相乗作用がみられた。血漿の中性脂肪量は、高カロリー飼料から低カロリー飼料に切り替えると肝臓で脂肪合成が亢進して、試験サンプル投与前に比べて試験終了後に対照群で顕著に増加したが、イソフラボン類・カルニチン混合物投与群とアルギニン・カフェイン混合物投与群は上昇が抑制され、さらに本発明品投与群は上昇が強く抑制され、相加的な作用がみられた。試験終了後の血漿の総コレステロール量は、対照群と比較してイソフラボン類・カルニチン混合物投与群とアルギニン・カフェイン混合物投与群は大差ないが、本発明品投与群は有意に低値を示し、相乗作用がみられた。これらの結果から、本発明のイソフラボン類、カルニチン、アルギニンおよびカフェインを含有する組成物は、明確な相乗作用があり、内臓脂肪・皮下脂肪の蓄積、脂肪合成の亢進に伴う高中性脂肪血症、肥満に伴う高コレステロール血症、およびメタボリックシンドロームなどの各症状の予防、改善または治療に有用であることが示された。 These results show the following. That is, the amount of increase / decrease in body weight and the amount of triglyceride in the liver are not significantly different between the group administered with the isoflavones / carnitine mixture and the group administered with the arginine / caffeine mixture compared with the control group, but significantly lower in the group administered with the present invention. A clear synergistic effect was observed. Subcutaneous fat and peri-mesenteric (visceral) adipose tissue weights were not significantly different in the group administered with isoflavones and carnitine compared to the control group, but were significantly lower in the group administered with arginine / caffeine. There was no. On the other hand, the product-administered group showed a significantly low value, and a clear synergistic effect was observed. Plasma triglyceride levels increased significantly in the control group after the end of the test compared to before administration of the test sample, but the isoflavones and carnitine increased when fat synthesis increased in the liver when switching from high calorie diet to low calorie diet. The increase was suppressed in the mixture administration group and the arginine / caffeine mixture administration group, and the increase was strongly suppressed in the product administration group of the present invention, and an additive action was observed. The plasma total cholesterol level after the end of the test is not significantly different between the isoflavones / carnitine mixture administration group and the arginine / caffeine mixture administration group compared to the control group, but the product administration group of the present invention shows a significantly lower value, A synergistic effect was observed. From these results, the composition containing the isoflavones of the present invention, carnitine, arginine and caffeine has a clear synergistic action, accumulation of visceral fat / subcutaneous fat, hypertriglyceremia associated with increased fat synthesis It has been shown to be useful for the prevention, amelioration or treatment of various symptoms such as hypercholesterolemia associated with obesity, and metabolic syndrome.
本発明の組成物は、脂肪肝、高脂血症(例えば、高中性脂肪血症、高コレステロール血症)などの脂質代謝異常や、内臓脂肪や皮下脂肪に起因する肥満を予防、改善、治療を目的とした、あるいはこれらの症状を伴うメタボリックシンドロームの予防、改善、治療を目的とした飲食品、医薬品、医薬部外品などとして有用である。 The composition of the present invention prevents, improves, and treats lipid metabolism abnormalities such as fatty liver and hyperlipidemia (for example, hypertriglyceremia, hypercholesterolemia) and obesity caused by visceral fat and subcutaneous fat. It is useful as a food / beverage product, drug, quasi-drug, etc. for the purpose of prevention, improvement, or treatment of metabolic syndrome associated with these symptoms.
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