JP2009221158A - Neutral fat reducing agent and body fat increase inhibitor - Google Patents
Neutral fat reducing agent and body fat increase inhibitor Download PDFInfo
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- JP2009221158A JP2009221158A JP2008067688A JP2008067688A JP2009221158A JP 2009221158 A JP2009221158 A JP 2009221158A JP 2008067688 A JP2008067688 A JP 2008067688A JP 2008067688 A JP2008067688 A JP 2008067688A JP 2009221158 A JP2009221158 A JP 2009221158A
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- catechin
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- theaflavin
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Abstract
【課題】安全性が高く、日常生活の中で無理なく継続摂取することができる、中性脂肪低減剤および体脂肪増加抑制剤を提供する。
【解決手段】テアフラビン、テアシネンシン、および数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体からなる群から選ばれる1種以上を有効成分として含有する中性脂肪低減剤および体脂肪増加抑制剤。
【選択図】図1[Problem] To provide a neutral fat reducing agent and a body fat increase inhibiting agent that are highly safe and can be continuously taken in daily life without difficulty.
A neutral fat reducing agent comprising as an active ingredient at least one selected from the group consisting of theaflavin, theasinensin, and a catechin oxidized polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200. And a body fat increase inhibitor.
[Selection] Figure 1
Description
本発明は中性脂肪低減剤および体脂肪増加抑制剤に関する。 The present invention relates to a neutral fat reducing agent and a body fat increase inhibitor.
最近、私たちの食事内容は高カロリーの物が多くなり、日常生活で体を動かす機会が少なくなり、このような栄養過剰と運動不足は、内臓、皮下、または血管内の脂肪を増やすことになる。血液中の中性脂肪とコレステロールが増加すると、動脈硬化が進行し狭心症や心筋梗塞などの虚血性心疾患、脳出血や脳梗塞などの脳卒中の原因になる。また、体脂肪が蓄積して肥満になると、糖尿病や急性膵炎、高血圧症、脂肪肝、痛風などの成人病を引き起こす。このような背景から、近年、特に健康の維持増進、疾病の予防治療に対する関心が高まり、脂肪や生活習慣病との関連についての研究が数多く行われるようになってきた。 Recently, our dietary content has been high in calories and has fewer opportunities to move the body in daily life, and such overnutrition and lack of exercise can lead to increased visceral, subcutaneous, or vascular fat. Become. When neutral fat and cholesterol in the blood increase, arteriosclerosis progresses, causing ischemic heart diseases such as angina pectoris and myocardial infarction, and strokes such as cerebral hemorrhage and cerebral infarction. Moreover, when body fat accumulates and becomes obese, it causes adult diseases such as diabetes, acute pancreatitis, hypertension, fatty liver and gout. Against this background, in recent years, interest in maintenance and promotion of health and prevention and treatment of diseases has increased, and many studies have been conducted on the relationship with fat and lifestyle-related diseases.
体脂肪や中性脂肪を減少させるにはストレスを減らし、適度な運動、バランスのとれた食生活、食物繊維、植物性タンパク質、多価不飽和脂肪酸を十分にとることが重要であると言われている。しかし、仕事が不規則なうえストレスの多い社会において、ストレスを減らし、適度な運動、バランスのとれた食事を毎日、摂取するのは非常に難しい。 It is said that to reduce body fat and neutral fat, it is important to reduce stress and take adequate exercise, a balanced diet, dietary fiber, vegetable protein, and polyunsaturated fatty acids. ing. However, in a society where work is irregular and stressful, it is very difficult to reduce stress, take moderate exercise and a balanced diet every day.
烏龍茶の脂質改善効果について、下記非特許文献1には、市販烏龍茶を1日1330mlずつ6週間飲用させ、血中中性脂肪値の有意な低下が認められたとの報告がある。また下記非特許文献2には、単純性肥満症の男女102名を対象に、烏龍茶(2g×4/日)を6週間連続経口摂取させた結果、67%の被験者に1kg以上の体重減少が認められ、さらに血中中性脂肪値が高値を示した被験者において烏龍茶接取後に有意な改善効果が認められたとの報告がある。
上記のように烏龍茶の大量飲用は血中の中性脂肪値の低下に効果が認められるものの、日常生活の中で大量飲用を続けていくのは難しい。飲む量を減らすために、単純に濃縮した烏龍茶を提供したとしても、苦味および渋みが強くカフェイン量も増えるため、現実的な方策としては適当ではない。
本発明は、上記事情に鑑みてなされたものであって、安全性が高く、日常生活の中で無理なく継続摂取することができる、中性脂肪低減剤および体脂肪増加抑制剤を提供することを目的とする。
As described above, drinking oolong tea in large quantities is effective in reducing the level of neutral fat in the blood, but it is difficult to continue drinking large quantities in daily life. Even if a simple concentrated oolong tea is provided to reduce the amount to drink, it is not suitable as a realistic measure because it has a strong bitterness and astringency and increases the amount of caffeine.
The present invention has been made in view of the above circumstances, and provides a neutral fat reducing agent and a body fat increase inhibiting agent that are highly safe and can be continuously ingested without difficulty in daily life. With the goal.
本発明者等は、茶の葉とビワ葉を一緒に揉みこんだ混合発酵茶葉の抽出液に中性脂肪を低減させる効果があることを見出し、それに着目して鋭意研究を重ねた結果、中性脂肪低減および体脂肪増加抑制に有効な成分を突き止めて本発明を完成するに至った。
すなわち本発明は、数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体、テアフラビン、およびテアシネンシンからなる群から選ばれる1種以上を有効成分として含有する中性脂肪低減剤を提供する。
前記中性脂肪低減剤は、少なくとも、数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体を有効成分として含有するか、または少なくとも、テアフラビンおよびテアシネンシンを有効成分として含有することが好ましい。
また本発明は、数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体、テアフラビン、およびテアシネンシンからなる群から選ばれる1種以上を有効成分として含有する体脂肪増加抑制剤を提供する。
前記体脂肪増加抑制剤は、少なくとも、数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体を有効成分として含有するか、または少なくとも、テアフラビンおよびテアシネンシンを有効成分として含有することが好ましい。
また本発明は、茶の葉とビワ葉を混合、揉捻し、発酵させた発酵茶葉から抽出される数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体を提供する。
The present inventors have found that an extract of mixed fermented tea leaves in which tea leaves and loquat leaves are mixed together have an effect of reducing neutral fat. The present inventors have completed the present invention by ascertaining ingredients effective in reducing sexual fat and suppressing increase in body fat.
That is, the present invention provides neutral fat reduction containing, as an active ingredient, at least one selected from the group consisting of a catechin oxidized polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200, theaflavin, and theasinensin. Provide the agent.
The neutral fat reducing agent contains at least a catechin oxidation polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200 as an active ingredient, or at least contains theaflavin and theasinensin as active ingredients It is preferable to do.
The present invention also provides an increase in body fat containing as an active ingredient at least one selected from the group consisting of a catechin oxidation polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200, theaflavin, and theacinensin. Provide the agent.
The body fat increase inhibitor contains at least a catechin oxidation polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200 as an active ingredient, or at least contains theaflavin and theasinensin as active ingredients It is preferable to do.
The present invention also provides a catechin oxidized polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200 extracted from a fermented tea leaf obtained by mixing, twisting and fermenting tea leaves and loquat leaves. .
本発明によれば、安全性が高く、日常生活の中で無理なく継続摂取することができる中性脂肪低減剤が得られる。
本発明によれば、安全性が高く、日常生活の中で無理なく継続摂取することができる体脂肪増加抑制剤が得られる。
本発明によれば、中性脂肪低減作用および体脂肪増加抑制を有する新規化合物としてのカテキン酸化重合体が得られる。
According to the present invention, it is possible to obtain a neutral fat reducing agent that is highly safe and can be continuously taken without difficulty in daily life.
ADVANTAGE OF THE INVENTION According to this invention, the body fat increase inhibitor which is high safety | security and can be continuously ingested easily in daily life is obtained.
According to the present invention, a catechin oxidized polymer as a novel compound having a neutral fat reducing action and a body fat increase suppression can be obtained.
本発明において、有効成分として用いられる(1)テアシネンシン、(2)テアフラビン、および(3)数平均分子量が5,970かつ重量平均分子量が13,200であるカテキン酸化重合体は、いずれも、茶の葉とビワ葉を原料として製造された混合発酵茶葉から得られる。
上記(3)カテキン酸化重合体は、後述の[実施例]に示されるように、茶葉に含まれる4種のカテキン(エピガロカテキン、エピカテキン、エピガロカテキンガレート、エピカテキンガレート)が酸化的に結合して生成した高分子化合物で、分子量は数平均分子量(Mn)5,970、重量平均分子量(Mw)13,200と推定される。一般に茶葉だけを発酵させて製造した紅茶にもカテキン酸化重合体が含まれるが、混合発酵茶葉から得られる上記(3)カテキン酸化重合体は、それよりも分子量が大きい。
In the present invention, (1) theacinensin, (2) theaflavin, and (3) a catechin oxidation polymer having a number average molecular weight of 5,970 and a weight average molecular weight of 13,200, which are used as active ingredients, are tea. It is obtained from mixed fermented tea leaves produced from the leaves and loquat leaves.
The above (3) catechin oxidation polymer is oxidative of four types of catechins (epigallocatechin, epicatechin, epigallocatechin gallate, epicatechin gallate) contained in tea leaves as shown in [Example] described later. The molecular weight is estimated to be a number average molecular weight (Mn) of 5,970 and a weight average molecular weight (Mw) of 13,200. Generally, black tea produced by fermenting only tea leaves also contains a catechin oxidized polymer, but the above (3) catechin oxidized polymer obtained from mixed fermented tea leaves has a higher molecular weight.
[混合発酵茶葉の製造方法]
混合発酵茶葉は、以下の方法で製造することができる。
原料として用いられる茶の葉は、いわゆるツバキ科の常緑低木Thea sinensis L.の葉である。この葉としては、一番茶以外に二番茶、三番茶、秋冬番茶、刈番茶なども使用でき、比較的多くのポリフェノール類を含む二番茶以降の安価な茶の葉のほうが好ましい。なお、これらの遅手の番茶は、現在価格が低迷し、かなりのものが廃棄されているが、このものを有効に利用できる。
[Production method of mixed fermented tea leaves]
Mixed fermented tea leaves can be produced by the following method.
The tea leaves used as the raw material are the so-called camellia evergreen shrub Thea sinensis L. Leaves. As this leaf, in addition to the first tea, second tea, third tea, autumn / winter ban tea, banban tea and the like can be used, and cheap tea leaves after the second tea containing a relatively large amount of polyphenols are preferred. The price of these late banchas is currently sluggish and a considerable amount is discarded, but this can be used effectively.
原料として用いられるビワ葉は、バラ科、植物名「ビワ」の葉であり、特に制限なく用いることができる。 The loquat leaves used as a raw material are leaves of the family Rosaceae and the plant name “Biwa”, and can be used without particular limitation.
混合発酵茶葉を製造するには、まずビワ葉および茶の葉を用意する。前処理として、ビワ葉および茶の葉を必要に応じて乾燥し、含水率を50〜60質量%程度としておくことが好ましい。また適宜の寸法、例えば1〜10mm角程度の大きさに切断しておくことが好ましい。 In order to produce mixed fermented tea leaves, first, loquat leaves and tea leaves are prepared. As pretreatment, it is preferable to dry loquat leaves and tea leaves as necessary, and to keep the water content at about 50 to 60% by mass. Moreover, it is preferable to cut | disconnect to an appropriate dimension, for example, a magnitude | size about 1-10 square mm.
次いで、茶の葉を乾燥し、水分量を減少させ、萎凋させる。この工程では、例えば粗揉機や、直火または電気で加熱した鍋または板状の器具を用い、茶の葉を撹拌しつつ、温度40〜150℃の加熱空気を茶の葉に当てる方法、密閉撹拌容器内に茶の葉を投入し、容器内の空気を吸引して内部を減圧状態として撹拌して乾燥する方法、萎凋槽を用いてネット上に散布した茶の葉の下方から通気する方法などが用いられる。
この萎凋により原料の茶の葉の含水率を45〜65質量%、好ましくは50〜60質量%程度に減少させると、次の揉捻工程で茶の葉から水分が揉み出され難くなるため、有効成分の流亡を防止できる。また後の乾燥工程が短縮できる点でも好ましい。
The tea leaves are then dried, the water content is reduced and wilted. In this process, for example, using a roughing machine, a pot or plate-like appliance heated directly or with electricity, stirring the tea leaves and applying heated air at a temperature of 40 to 150 ° C. to the tea leaves, sealing A method in which tea leaves are put into a stirring container, the air in the container is sucked and the inside is decompressed and stirred and dried, and a method in which air is blown from below the tea leaves sprayed on the net using a wilt tank Etc. are used.
If the moisture content of the raw tea leaves is reduced to 45 to 65% by mass, preferably about 50 to 60% by this wilting, it will be difficult to ooze water from the tea leaves in the next twisting step. Prevents the loss of ingredients. It is also preferable in that the subsequent drying step can be shortened.
次いで、萎凋工程を経た原料の茶の葉を加圧しながら揉む(揉捻する)とともに、この揉捻時にビワ葉を添加して、両者を一緒に揉捻する。ビワ葉は茶の葉の揉捻開始と同時に添加してもよく、あるいは一定時間茶の葉のみの揉捻を行った後、びわ葉を添加してさらに揉捻してもよい。全揉捻時間のうち、揉捻開始から0〜40%の時間が経過したのち、ビワ葉を添加することが好ましい。ビワ葉を揉捻工程の最初から添加しておくことがより好ましい。
この揉捻により、茶の葉およびビワ葉の組織が破壊され、茶の葉に含まれるポリフェノールオキシダーゼなどの酸化酵素が茶の葉およびビワ葉に含まれるポリフェノールを酸化、重合し、酸化重合物が生成する。
Next, the raw tea leaves that have undergone the wilting process are massaged while being pressed (twisted), and loquat leaves are added at the time of this twisting, and both are twisted together. Loquat leaves may be added simultaneously with the start of tea leaf twisting, or after only tea leaf twisting for a certain period of time, loquat leaves may be added and further twisted. It is preferable to add loquat leaves after 0 to 40% of the total twisting time has elapsed since the start of twisting. It is more preferable to add loquat leaves from the beginning of the twisting process.
This twisting destroys the tissue of tea leaves and loquat leaves, and oxidative enzymes such as polyphenol oxidase contained in tea leaves oxidize and polymerize polyphenols contained in tea leaves and loquat leaves, producing an oxidized polymer. To do.
ビワ葉の添加量は、ビワ葉/茶の葉の絶乾質量比が、5/95〜35/65の範囲が好ましく、8/92〜25/75の範囲がより好ましい。ビワ葉の添加量が上記範囲内であれば、上記(1)〜(3)の有効成分が効率良く得られ、特に上記(3)カテキン酸化重合体が効率良く生成する。
揉捻は、茶の葉の揉捻に用いられている通常の揉捻機を用いる方法など、公知の方法を適宜採用できる。揉捻時間は15〜25分が好ましい。揉捻時の原料の温度は20〜40℃が好ましい。20℃未満では発酵不足となり、40℃を越えると上記(1)〜(3)の有効成分が効率良く得られない。
The amount of loquat leaves added is preferably in the range of 5/95 to 35/65, more preferably 8/92 to 25/75. If the amount of loquat leaves added is within the above range, the active ingredients (1) to (3) can be obtained efficiently, and particularly the (3) catechin oxidized polymer is efficiently produced.
For the twisting, a known method such as a method using a normal twisting machine used for twisting tea leaves can be appropriately employed. The twisting time is preferably 15 to 25 minutes. The temperature of the raw material during twisting is preferably 20 to 40 ° C. If it is less than 20 ° C., fermentation is insufficient, and if it exceeds 40 ° C., the active ingredients (1) to (3) cannot be obtained efficiently.
次いで発酵工程を行う。すなわち、揉捻後の混合原料を数cmの厚さに堆積させた状態で、温度20〜27℃、湿度30〜60%RHの発酵室内などの環境下に静置する。なお、茶類の製造工程における「発酵」とは葉中の酸化酵素による酸化反応を意味する。
発酵時間は0〜4時間が好ましい。揉捻工程の時間は発酵工程に含めない。先の揉捻工程において、揉捻の開始と同時に発酵が開始するため、揉捻工程とは別に発酵工程を設けなくても、すなわち発酵時間が0時間でも、発酵した混合発酵茶葉を得ることができる。
Next, the fermentation process is performed. That is, in a state where the mixed raw material after twisting is deposited to a thickness of several centimeters, the mixture is left in an environment such as a fermentation chamber at a temperature of 20 to 27 ° C. and a humidity of 30 to 60% RH. “Fermentation” in the tea production process means an oxidation reaction by oxidase in leaves.
The fermentation time is preferably 0 to 4 hours. The time for the twisting process is not included in the fermentation process. In the previous twisting process, fermentation starts simultaneously with the start of the twisting process, so that a fermented mixed fermented tea leaf can be obtained even if a fermentation process is not provided separately from the twisting process, that is, even if the fermentation time is 0 hours.
次いで、所定の発酵時間が経過したならば、原料を加熱して発酵を止め、乾燥する。例えば、連続式乾燥機に原料を投入し、これに温度80〜120℃の熱風を吹き込み、排気温度が50〜60℃となるように操作する。加熱時間は10〜30分程度で十分であり、これにより原料中の含水率を5質量%程度とする。 Next, when a predetermined fermentation time has elapsed, the raw material is heated to stop the fermentation and dried. For example, raw materials are put into a continuous dryer, hot air having a temperature of 80 to 120 ° C. is blown into the continuous dryer, and the exhaust temperature is controlled to be 50 to 60 ° C. A heating time of about 10 to 30 minutes is sufficient, so that the water content in the raw material is about 5% by mass.
こうして混合発酵茶葉が得られる。本発明で用いられる混合発酵茶葉は、加熱工程後の荒茶でもよく、これに必要に応じて仕上げ加工を施した仕上げ茶でもよく、荒茶または仕上げ茶を適宜の大きさに粉砕して粉末状としたものでもよい。 In this way, mixed fermented tea leaves are obtained. The mixed fermented tea leaves used in the present invention may be crude tea after the heating step, or may be finished tea that has been subjected to finishing processing as necessary, and the crude tea or finished tea is pulverized to an appropriate size and powdered. It may be a shape.
[有効成分の分画]
混合発酵茶葉を抽出し、該抽出液から有効成分(1)〜(3)を分画する。抽出溶媒は水または有機溶媒が用いられる。有機溶媒の具定例としてはメタノール、エタノール、アセトン等が挙げられる。
抽出方法および抽出液から有効成分を分画する方法は特に制限されないが、図1に示す方法で行うと有効成分(1)〜(3)を効率良く得ることができる。
[Fractionation of active ingredients]
Mixed fermented tea leaves are extracted, and active ingredients (1) to (3) are fractionated from the extract. As the extraction solvent, water or an organic solvent is used. Specific examples of the organic solvent include methanol, ethanol, acetone and the like.
The extraction method and the method for fractionating the active ingredient from the extract are not particularly limited, but the active ingredients (1) to (3) can be efficiently obtained by the method shown in FIG.
まず、抽出溶媒として水を用いて混合発酵茶葉の抽出を行い、固液分離を行って抽出液1と残滓2を得る。水の温度は10〜25℃程度が好ましい。この工程では主に糖・カフェイン糖が抽出される。有効成分(1)〜(3)を含むポリフェノール類の一部も抽出される。得られた抽出液1を、セファデックスLH−20カラムを用いたゲルパーミエーションクロマトグラフイーに供し、糖およびカフェイン類を透過させ、ポリフェノール類だけを吸着させる。
一方、上記残滓2を有機溶媒で抽出して抽出液3を得る。この工程で、水抽出後の茶葉(残滓2)に含まれるポリフェノール類が抽出される。抽出液3を得る際は、抽出操作後に有機溶媒を除去して濃縮し、さらに不要な固形分(残渣4)を取り除いて抽出液3とすることが好ましい。こうして得られた抽出液3を、前記抽出液1の処理を終えたセファデックスLH−20カラムに通し、低いアルコール濃度の溶媒を用いて残存する糖、カフェイン、フラボノール配糖体を洗い流し、アルコール濃度を上げて有効成分を溶出させ、上記(1)テアシネンシン、(2)テアフラビン、及び(3)カテキン酸化重合体を含むフラクション2を得る。
First, mixed fermented tea leaves are extracted using water as an extraction solvent, and solid-liquid separation is performed to obtain an
On the other hand, the
次に、得られたフラクション2を、7M尿素−アセトン混合液を溶媒とするセファデックスLH−20カラムを用いたゲルパーミエーションクロマトグラフィーにより、分子量が大きいカテキン酸化重合体を含むフラクション2−1と、分子量が比較的小さいテアシネンシンとテアフアラビンを含むフラクション2−2に分画する。
フラクション2−1からアセトンを留去して水溶液として、ダイアイオンHP20SSカラムを用いたゲルパーミエーションクロマトグラフィーに供し、尿素と塩酸を水で洗い流し、アルコールでポリフェノールを溶出することにより、目的とする(3)カテキン酸化重合体のフラクション3−1が得られる。
一方、フラクション2−2もアセトンを留去した後、ダイアイオンHP20SSカラムを用いたゲルパーミエーションクロマトグラフィーに供し、尿素と塩酸を水で洗い流した後、アルコール濃度を増加させながらアルコールで溶出することにより、テアシネンシン類とテアフラビン類が分離され、目的とする(1)テアシネンシンのフラクション3−1、および(2)テアフラビンのフラクション3−3が得られる。
Next, the obtained
Acetone is distilled off from the fraction 2-1, which is used as an aqueous solution for gel permeation chromatography using a Diaion HP20SS column. The urea and hydrochloric acid are washed away with water, and the polyphenol is eluted with alcohol. 3) A fraction 3-1 of the catechin oxidized polymer is obtained.
On the other hand, fraction 2-2 is also subjected to gel permeation chromatography using a Diaion HP20SS column after distilling off acetone, and after rinsing urea and hydrochloric acid with water, eluting with alcohol while increasing the alcohol concentration. As a result, theacinensins and theaflavins are separated, and the desired (1) fraction 3-1 of theacinensin and (2) fraction 3-3 of theaflavin are obtained.
図1に示す抽出および分画方法にあっては、まず混合発酵茶葉を水で抽出して、水溶性成分を多く含み、ポフェノール類の含有量が少ない抽出液1を得るため、該抽出液を濃縮せずにカラムに通して糖およびカフェイン類を容易に分離・除去することができる。仮に、カラムに通す抽出液に糖分が高濃度で含まれていると、ゲルの収縮が生じ易くカラムへの負荷が大きくなるが、上記の方法では、かかる不都合を防止できる。また抽出液を濃縮する手間も省ける。
また、フラクション2の分画に、7M尿素−アセトン混液を溶媒とするセファデックスLH−20を用いたゲルパーミエーションクロマトグラフィーを適用することにより、1段階で分子量が大きい(3)カテキン酸化重合体を含むフラクション2−1と、分子量が比較的小さい(1)テアシネンシンと(2)テアフアラビンを含む画分であるフラクション2−2に分けることができる。
さらに、フラクション2−2から尿素を除く段階でダイアイオンHP20SSカラムクロマトを用いることにより、(1)テアシネンシン類と(2)テアフラビン類が分離されて溶出され、極めて効率的に目的の有効成分を得ることができる。
In the extraction and fractionation method shown in FIG. 1, first, mixed fermented tea leaves are extracted with water to obtain an
Further, by applying gel permeation chromatography using Sephadex LH-20 with 7M urea-acetone mixture as a solvent to
Furthermore, by using Diaion HP20SS column chromatography at the stage of removing urea from fraction 2-2, (1) theacinensins and (2) theaflavins are separated and eluted, and the target active ingredient is obtained very efficiently. be able to.
[中性脂肪低減剤および体脂肪増加抑制剤]
このようにして得らえる上記(1)テアシネンシン、(2)テアフラビン、及び(3)カテキン酸化重合体をそれぞれ含むフラクションは、そのまま本発明の中性脂肪低減剤または体脂肪増加抑制剤(以下、総称して本発明の剤ということがある。)として用いることができる。該フラクションに対して、溶媒除去、濃縮、乾燥等の後処理を適宜施したものを本発明の剤の有効成分として用いてもよい。
本発明の剤は、上記(1)テアシネンシン、(2)テアフラビン、及び(3)カテキン酸化重合体からなる群から選ばれる1種以上を有効成分として含有する。これらはいずれか一種でもよく、2種以上を併用してもよい。特に(1)テアシネンシンと(2)テアフラビンを併用すると効果が大きく向上する。(3)カテキン酸化重合体は単独で用いても優れた効果が得られる点で特に好ましい。
(1)テアシネンシンと(2)テアフラビンを併用する場合、各成分の含有量は特に限定されないが、両者の合計を100質量%とするとき、そのうちの30〜90質量%がテアシネンシンで、残部がテアフラビンであることが好ましい。該テアシネンシンのより好ましい含有割合は50〜90質量%であり、70〜80質量%がさらに好ましい。
本発明の剤は、上記有効成分(1)〜(3)の他に、賦形剤、結合剤、崩壊剤、滑沢剤、防腐剤、安定剤、保存剤、矯味矯臭剤、希釈剤、香味剤等の、製剤上許容される1または2種類以上の添加剤を含有してもよい。また、中性脂肪低減作用または体脂肪増加抑制作用を有し、安全性が確認されている公知の成分を含有させてもよい。
[Neutral fat reducing agent and body fat increase inhibitor]
The fractions containing (1) theacinensin, (2) theaflavin, and (3) catechin oxidized polymer obtained in this way are the neutral fat reducing agent or body fat increase inhibitor (hereinafter referred to as “the body fat increasing agent”) of the present invention. Collectively, it may be referred to as the agent of the present invention). Those obtained by appropriately performing post-treatment such as solvent removal, concentration, and drying on the fraction may be used as an active ingredient of the agent of the present invention.
The agent of the present invention contains one or more selected from the group consisting of (1) theacinensin, (2) theaflavin, and (3) catechin oxidized polymer as an active ingredient. Any of these may be used alone, or two or more of these may be used in combination. In particular, when (1) theacinensin and (2) theaflavin are used in combination, the effect is greatly improved. (3) The catechin oxidized polymer is particularly preferable in that an excellent effect can be obtained even when used alone.
When (1) theacinensin and (2) theaflavin are used in combination, the content of each component is not particularly limited, but when the total of both is 100% by mass, 30 to 90% by mass of theasinensin and the remainder is theaflavin It is preferable that A more preferable content ratio of the theasinensin is 50 to 90% by mass, and more preferably 70 to 80% by mass.
In addition to the active ingredients (1) to (3), the agent of the present invention includes excipients, binders, disintegrants, lubricants, preservatives, stabilizers, preservatives, flavoring agents, diluents, You may contain 1 or 2 or more types of additives accept | permitted on formulation, such as a flavoring agent. Moreover, you may contain the well-known component which has a neutral fat reduction effect | action or a body fat increase inhibitory effect, and the safety | security has been confirmed.
本発明の剤は、これを経口投与することにより、血液中の中性脂肪濃度を低減させる効果、肝臓中の中性脂肪濃度を低減させる効果、および/または体脂肪の増加を抑制する効果が得られる。投与方法は特に制限されるものではないが、2週間以上の期間にわたって継続的に投与することが好ましい。
本発明の剤の有効投与量は、成人1日当たりの投与量が、(1)テアフラビン、(2)テアシネンシンおよび(3)カテキン酸化重合体の総量として、10〜5000mgが好ましく、50〜2000mgがより好ましく、50〜700mgがさらに好ましい。
本発明の剤の剤形は、特に制限されないが錠剤、顆粒剤、カプセル剤、水薬、ドリンク剤等の内服剤形とすることが好ましい。このような製剤化は、医薬の製造に用いられる常法に従って行うことができる。
The agent of the present invention has the effect of reducing the triglyceride concentration in the blood, the effect of reducing the triglyceride concentration in the liver, and / or the effect of suppressing the increase in body fat by orally administering it. can get. The administration method is not particularly limited, but it is preferable to administer continuously over a period of 2 weeks or more.
The effective daily dose of the agent of the present invention is preferably 10 to 5000 mg, more preferably 50 to 2000 mg as a total daily dose of (1) theaflavin, (2) theacinensin and (3) catechin oxidized polymer. Preferably, 50 to 700 mg is more preferable.
The dosage form of the agent of the present invention is not particularly limited, but is preferably an internal dosage form such as a tablet, granule, capsule, liquid medicine, drink or the like. Such formulation can be carried out according to a conventional method used for the production of a medicine.
以下において「%」は特に断りのない限り「質量%」である。
以下において原料として用いた「茶の葉」はいずれも長崎県総合農林試験場東彼杵茶葉支場で栽培したヤブキタ種の三番茶の葉である。
[参考例1:混合発酵茶葉の製造]
茶の葉にビワ葉を投入し、揉捻機で揉み込んだ。茶の葉とビワ葉の配合割合は茶の葉:ビワ茶の絶乾質量比が9:2とした。揉み込みの時間は20分とし、揉捻時の原料の温度は33℃とした。この後、直ちに熱風式乾燥機内に移し、100℃で30分間加熱することにより、発酵を止めるとともに乾燥した。こうして含水率5質量%の混合発酵茶葉を得た。
In the following, “%” is “% by mass” unless otherwise specified.
The "tea leaves" used as raw materials in the following are all the third tea leaves of Yabukita cultivated at the Nagasaki Prefectural Agricultural and Forestry Experiment Station Higashisonobe Tea Leaf Branch.
[Reference Example 1: Production of mixed fermented tea leaves]
The loquat leaves were put into the tea leaves and swallowed with a twister. The blending ratio of tea leaves and loquat leaves was a tea leaf: lowa dry tea mass ratio of 9: 2. The squeezing time was 20 minutes, and the temperature of the raw material during twisting was 33 ° C. After this, it was immediately transferred into a hot air drier and heated at 100 ° C. for 30 minutes to stop fermentation and dry. Thus, a mixed fermented tea leaf having a water content of 5% by mass was obtained.
<製造例1>
(抽出および分画)
図1に示す手順で、有効成分の抽出および分画を行った。
まず、参考例1で得た混合発酵茶葉1930gを水(15℃)30Lに浸し、室温で2日間抽出した後吸引ろ過した。得られたろ液(抽出液1)を、水で置換したセファデックスLH−20カラム(ファルマシア・ファイン・ケミカル社製、ゲル直径10cm、長さ35cm)にそのまま流し込み、ポリフェノールを吸着させた。
一方、残滓2として得られる、水抽出後の茶葉は、50%アセトン水溶液(アセトン:水の容量比=1:1)30Lで、2日間、室温での抽出を2回繰り返し、2回分のろ液を合わせてロータリーエバポレーターでアセトンを留去した。得られた沈殿を含む溶液に20容量%の濃度となるようにメタノールを加えて攪拌し、溶けずに残ったクロロフィルなどをろ過して除いた。得られたろ液(抽出液3)を、上記抽出液1を通導したセファデックスLH−20カラムに続けて流し込んだ。
次いでカラムに40%メタノール(メタノール:水の容量比=4:6、以下同様。)の2Lを流し、糖類、カフェイン及びフラボノール配糖体を流出させた。さらにカラムに60%メタノールの2L、80%メタノールの2L、100%メタノールの4L、メタノール−アセトン−水混合液(メタノール:アセトン:水の容量比=8:1:1)の2L、およびアセトン水混合液(アセトン:水の容量比=6:2)の6Lを、この順に流して成分を溶出させた。溶出液は250mlずつガラス容器に分け取り、それぞれについて蛍光剤入りシリカゲル薄層クロマトグラフィー(展開溶媒はトルエン:ギ酸エチル:ギ酸の容量比=1:7:1の混合液、検出は紫外吸収、及び塩化鉄(III)試薬噴霧)で成分を確認し、分画ロータリーエバポレーターで濃縮乾固した。
こうして、主にカテキン類を含むフラクション1(52.3g)と、テアシネンシン、テアフラビン、及びカテキン酸化重合体を含むフラクション2(74.6g)を得た。
<Production Example 1>
(Extraction and fractionation)
The active ingredient was extracted and fractionated by the procedure shown in FIG.
First, 1930 g of mixed fermented tea leaves obtained in Reference Example 1 were immersed in 30 L of water (15 ° C.), extracted at room temperature for 2 days, and then suction filtered. The obtained filtrate (Extract 1) was poured into a Sephadex LH-20 column (Pharmacia Fine Chemicals, gel diameter: 10 cm, length: 35 cm) substituted with water to adsorb polyphenol.
On the other hand, the tea leaves after water extraction obtained as
Next, 2 L of 40% methanol (methanol: water volume ratio = 4: 6, the same applies hereinafter) was allowed to flow through the column, and sugars, caffeine and flavonol glycosides were allowed to flow out. Furthermore, 2 L of 60% methanol, 2 L of 80% methanol, 4 L of 100% methanol, 2 L of methanol-acetone-water mixture (volume ratio of methanol: acetone: water = 8: 1: 1), and acetone water 6 L of the mixture (acetone: water volume ratio = 6: 2) was flowed in this order to elute the components. The eluate was divided into glass containers of 250 ml each, and for each, silica gel thin layer chromatography containing a fluorescent agent (developing solvent was a mixture of toluene: ethyl formate: formic acid volume ratio = 1: 7: 1, detection was ultraviolet absorption, and The components were confirmed by iron (III) chloride spraying, and concentrated to dryness with a fractional rotary evaporator.
Thus, a fraction 1 (52.3 g) mainly containing catechins and a fraction 2 (74.6 g) containing theacinensin, theaflavin, and a catechin oxidized polymer were obtained.
フラクション2は7M尿素−アセトン混合液(尿素:アセトンの容量比=2:3、塩酸でpH2に調整)に溶解し、同じ溶媒で置換したセファデックスLH−20カラム(ゲル直径10cm、長さ35cm)に流し込み、カテキン酸化重合体を含むフラクション2−1とテアシネンシンとテアフラビンを含むフラクション2−2に分画した。
フラクション2−1はアセトンを留去して水溶液とし、ダイアイオンHP20SSカラム(三菱化学社製、ゲル直径5cm長さ30cm)に流し込み、尿素と塩酸を水で洗い流した後、メタノールでポリフェノールを溶出してカテキン酸化重合体のフラクション3−1(21.4g)を得た。
フラクション2−2もアセトンを留去した後、ダイアイオンHP20SSカラム(ゲル直径5cm長さ30cm)に流し込み、尿素と塩酸を水で洗い流した後、10%メタノールの0.5L、20%メタノールの0,5L、30%メタノールの0,5L、40%メタノールの0,5L、60%メタノールの0,5L、80%メタノールの0,5Lで溶出させ、テアシネンシンのフラクション3−2(8.5g)、その他のポリフェノール混合物のフラクション(7.4g、図示せず)、およびテアフラビン類を主成分とするフラクション3−3(30.1g)を得た。
Fraction 2-1 distills acetone to form an aqueous solution, which is poured into a Diaion HP20SS column (Mitsubishi Chemical Co., Ltd., gel diameter: 5 cm, length: 30 cm). Urea and hydrochloric acid are washed away with water, and then polyphenol is eluted with methanol. Thus, fraction 3-1 (21.4 g) of the catechin oxidized polymer was obtained.
Fraction 2-2, after distilling acetone off, was poured into a Diaion HP20SS column (
(同定)
得られたフラクションのHPLC(高速液体クロマトグラフィー)によるクロマトグラムを図2に示す。図2の(A)はカテキン酸化重合体のフラクション3−1、(B)はテアシネンシンのフラクション3−2、(C)はテアフラビン類のフラクション3−3についてのクロマトグラムである。
各試料のHPLC分析条件は以下の通りである。
[カテキン酸化重合体及びテアシネンシンの分析]
カラム:Cosmosil 5C18 ARII(ナカライテスク社製、4.6×250mm)、
カラム温度:35℃、
移動相:A;50mMリン酸、B;CH3CN、B 4%から30%(39分間)、30%から75%(15分間)、
流速:0.8ml/min。
[テアフラビン類の分析]
カラム:Cosmosil 5C18 PAQ(ナカライテスク社製、4.6×250mm)、
カラム温度:35℃、
移動相:A;50mMリン酸、B;CH3CN、B 10%から25%(5分間)、25%から80%(40分間)、
流速:0.8ml/min。
(Identification)
A chromatogram of the obtained fraction by HPLC (high performance liquid chromatography) is shown in FIG. 2A is a chromatogram for the catechin oxidized polymer fraction 3-1, FIG. 2B is the theacinensin fraction 3-2, and FIG. 2C is the theaflavin fraction 3-3.
The HPLC analysis conditions for each sample are as follows.
[Analysis of Catechin Oxidation Polymer and Theacinensin]
Column: Cosmosil 5C 18 ARII (manufactured by Nacalai Tesque, 4.6 × 250 mm),
Column temperature: 35 ° C.
Mobile phase: A; 50 mM phosphoric acid, B; CH 3 CN, B 4% to 30% (39 minutes), 30% to 75% (15 minutes),
Flow rate: 0.8 ml / min.
[Analysis of theaflavins]
Column: Cosmosil 5C 18 PAQ (manufactured by Nacalai Tesque, 4.6 × 250 mm),
Column temperature: 35 ° C.
Mobile phase: A; 50 mM phosphoric acid, B; CH 3 CN,
Flow rate: 0.8 ml / min.
テアシネンシンおよびテアフラビン類は標準品とHPLCクロマトグラフを比較することにより同定した。
図2に示されるように、フラクション3−2の主成分はテアシネンシンA、フラクション3−3の主成分はテアフラビン類である。
テアシネンシンAおよびテアフラビン類の構造式を図3に示す。テアフラビン類のうち、TFは構造式中のR1とR2が水素原子であるもの、TF3GはR1がガロイル基(galloyl)でR2が水素原子であるもの、TF3’GはR1が水素原子でR2がガロイル基であるもの、TFdiGはR1とR2がガロイル基であるものをそれぞれ示す。
Theasinensins and theaflavins were identified by comparing the standards with HPLC chromatographs.
As shown in FIG. 2, the main component of the fraction 3-2 is theasinensin A, and the main component of the fraction 3-3 is theaflavins.
The structural formulas of theacinensin A and theaflavins are shown in FIG. Among the theaflavins, TF is a compound in which R 1 and R 2 in the structural formula are hydrogen atoms, TF3G is a compound in which R 1 is a galloyl group and R 2 is a hydrogen atom, and TF3′G is a compound in which R 1 is R 1. A hydrogen atom in which R 2 is a galloyl group and TFdiG are those in which R 1 and R 2 are galloyl groups.
(分子量の測定)
上記で得られたカテキン酸化重合体をジメチルホルムアミドに溶解し、ゲルろ過用高速液体クロマトグラフィーで分析した。分析条件は以下の通りとした。
カラム:TSK−gel−α 3000カラム、長さ300mm×径7.8mm、(東ソー社製)、
流速:0.5ml/min、
溶媒:10mM塩化リチウムを含むジメチルホルムアミド、
温度:40℃、
検出:254nmにおける紫外吸収。
ピークトップの保持時間から分子量を推定した。分子量標準品としては、ポリスチレン標準品(分子量4,000、25,000、50,000、及び170,000)、トルエン(分子量92)を用いた。その結果、得られたカテキン酸化重合体の分子量は、数平均分子量(Mn)が5,970、重量平均分子量(Mw)が13,200であった。
(Measurement of molecular weight)
The catechin oxidized polymer obtained above was dissolved in dimethylformamide and analyzed by high performance liquid chromatography for gel filtration. The analysis conditions were as follows.
Column: TSK-gel-α 3000 column, length 300 mm × diameter 7.8 mm (manufactured by Tosoh Corporation),
Flow rate: 0.5 ml / min
Solvent: dimethylformamide containing 10 mM lithium chloride,
Temperature: 40 ° C
Detection: UV absorption at 254 nm.
The molecular weight was estimated from the retention time of the peak top. As molecular weight standard products, polystyrene standard products (molecular weights 4,000, 25,000, 50,000, and 170,000) and toluene (molecular weight 92) were used. As a result, the number average molecular weight (Mn) of the obtained catechin oxidized polymer was 5,970, and the weight average molecular weight (Mw) was 13,200.
<比較製造例1>
製造例1において、混合発酵茶葉に代えて市販紅茶を用いた他は、同様の処理を行って得られたフラクション3−1について、同様にして分子量を測定したところ、数平均分子量(Mn)が2,062、重量平均分子量(Mw)が10,413であった。
<Comparative Production Example 1>
In Production Example 1, the molecular weight was measured in the same manner for the fraction 3-1, which was obtained by carrying out the same treatment except that a commercial black tea was used instead of the mixed fermented tea leaf, and the number average molecular weight (Mn) was It was 2,062 and the weight average molecular weight (Mw) was 10,413.
<測定例1>
製造例1で得られたカテキン酸化重合体を、重水を5%含む重アセトンに溶解し、13C−NMRスペクトルを測定した。その結果を図4に示す。
比較のために、紅茶の高分子ポリフェノールおよび新鮮ビワ葉から得られたプロシアニジン(エピカテキンが酸化的に重合したもの)について、同様にして13C−NMRスペクトルを測定した。その結果を図4に示す。
図4の(A)は製造例1で得られたカテキン酸化重合体、(B)は紅茶の高分子ポリフェノール、(C)はビワ葉のプロシアニジンについてのスペクトルである。
この図の結果より、製造例1で得られたカテキン酸化重合体は、紅茶高分子ポリフェノールの特徴的シグナルとビワ葉プロシアニジンの特徴的シグナルの両方を併せ持つことがわかる。このことから、ビワ葉に含まれるプロシアニジンが茶カテキンと共重合していると考えられる。
製造例1で得られたカテキン酸化重合体の推定部分構造式を図5に示す。該推定部分構造式は、カテキンを酵素酸化して得られる物質の化学構造(Li,Y.,et.al.,Pytochemistry,2007,68,1081;Kusano,R.,et.al.,Chem.Pharm.Bull.,2007,56,1768)と、ビワ葉プロアントシアニジンの構造をもとに推定した。
<Measurement Example 1>
The catechin oxidation polymer obtained in Production Example 1 was dissolved in heavy acetone containing 5% heavy water, and a 13 C-NMR spectrum was measured. The result is shown in FIG.
For comparison, 13 C-NMR spectra were measured in the same manner for procyanidins (epicatechin polymerized epicatechin) obtained from black tea polymer polyphenols and fresh loquat leaves. The result is shown in FIG.
(A) of FIG. 4 is a spectrum about the catechin oxidation polymer obtained by manufacture example 1, (B) is a high molecular weight polyphenol of black tea, (C) is a spectrum about procyanidins of loquat leaves.
From the result of this figure, it can be seen that the catechin oxidized polymer obtained in Production Example 1 has both the characteristic signal of black tea polymer polyphenol and the characteristic signal of loquat procyanidin. This suggests that procyanidins contained in loquat leaves are copolymerized with tea catechins.
The estimated partial structural formula of the catechin oxidized polymer obtained in Production Example 1 is shown in FIG. The deduced partial structural formula is the chemical structure of a substance obtained by enzymatic oxidation of catechin (Li, Y., et. Al., Pytochemistry, 2007, 68, 1081; Kusano, R., et. Al., Chem. Pharm. Bull., 2007, 56, 1768) and the structure of loquat leaf proanthocyanidins.
<試験例1:血清中性脂肪および肝臓中性脂肪に対する効果>
製造例1で得られたテアシネンシン、テアフラビン、およびカテキン酸化重合体を用い、肥満を呈するマウスにこれらの成分を含む食餌を摂取させたときの、血清中性脂肪濃度および肝臓中性脂肪濃度に及ぼす影響を調べた。
実験動物として、4週齢の肥満を呈するKK−Ayマウスを用い、室温22±1℃、湿度55±5%、8:00〜20:00点灯のライトサイクルの動物飼育室で飼育した。KK−Ayマウスは、5週齢までは、市販のMF固形飼料(オリエンタル酵母(株)製)を与えて予備飼育をし、その後試験食の摂食を開始した。
すなわち、5週齢の時に平均体重が同じになるように1群6匹ずつ、(I)群〜(VI)群の合計6群に群分けし、以下の試験食を6週間自由摂食させた。
試験食は、AIN−76に基づいた純化食をコントロール食とした。その組成(単位:g/kg)は、カゼイン200、コーン油100、ミネラル混合(AIN−76−MX)35、ビタミン混合(AIN−76−VX)10、セルロース50、重酒石酸コリン2、DL−メチオニン3、コーンスターチ150およびショ糖450である。
(I)群:コントロール食をそのまま試験食として摂取させた。
(II)群:コントロール食に0.03%のテアシネンシンを添加し、その添加分だけショ糖を減じた試験食。
(III)群:コントロール食に0.02%のテアフラビンを添加し、その添加分だけショ糖を減じた試験食。
(IV)群:コントロール食に0.03%のテアシネンシンと0.02%のテアフラビンの両方を添加し、その添加分だけショ糖を減じた試験食。
(V)群:コントロール食に0.1%のカテキン酸化重合体を添加し、その添加分だけショ糖を減じた試験食。
(VI)群:コントロール食に0.5%のカテキン酸化重合体を添加し、その添加分だけショ糖を減じた試験食。
いずれの群も飼育期間中、摂食量は毎日測定し、体重は1日おきに測定した。試験食の摂取を開始してから6週間後の血清中性脂肪濃度と肝臓中性脂肪濃度を表1に示す。
<Test Example 1: Effect on serum neutral fat and liver neutral fat>
Using the theacinensin, theaflavin, and the catechin oxidized polymer obtained in Production Example 1, effects on serum triglyceride concentration and hepatic triglyceride concentration when mice containing obesity are fed a diet containing these components The effect was investigated.
KK- Ay mice exhibiting obesity at 4 weeks of age were used as experimental animals and were bred in an animal breeding room with a light cycle of room temperature 22 ± 1 ° C., humidity 55 ± 5%, and 8:00:00 to 20:00 lighting. Up to 5 weeks of age, KK-A y mice were preliminarily fed with a commercially available MF chow (produced by Oriental Yeast Co., Ltd.), and then started eating test foods.
That is, each group is divided into 6 groups (groups (I) to (VI)) so that the average weight is the same at the age of 5 weeks, and the following test meals are allowed to eat freely for 6 weeks. It was.
As the test meal, a purified meal based on AIN-76 was used as a control meal. The composition (unit: g / kg) is:
Group (I): A control diet was directly taken as a test diet.
Group (II): A test meal in which 0.03% of theacinensin was added to the control meal and sucrose was reduced by the added amount.
Group (III): A test meal in which 0.02% theaflavin was added to the control meal and sucrose was reduced by the added amount.
Group (IV): A test meal in which both 0.03% theasinensin and 0.02% theaflavin were added to the control meal, and sucrose was reduced by the added amount.
Group (V): A test meal in which 0.1% catechin oxidized polymer was added to the control meal and sucrose was reduced by the added amount.
Group (VI): A test meal in which 0.5% catechin oxidized polymer was added to the control meal and sucrose was reduced by the added amount.
In each group, during the breeding period, the amount of food intake was measured every day, and the body weight was measured every other day. Table 1 shows the serum triglyceride concentration and
表1の結果より、血清中性脂肪濃度については、コントロール食を摂取した(I)群のKK−Ayマウスと、0.03%テアシネンシン食あるいは0.02%テアフラビン食を単独で摂取した(II)群または(III)群のマウスとで、ほとんど変わらなかった。
一方、0.03%テアシネンシンと0.02%テアフラビンの両方を含む食餌を摂取した(IV)群のマウスは、(I)群のマウスに比べて血清中性脂肪濃度が大きく低下した。
また、0.1%あるいは0.5%のカテキン酸化重合物を含む食餌を摂取した(V)群と(VI)群のKK−Ayマウスは、いずれも(I)群のマウスに比べて血清中性脂肪濃度が低下した。
肝臓中性脂肪濃度は、(I)群に比べて、いずれの群も低下しており、特に、(IV)、(V)、(VI)群の低下が大きく、中でも0.03%テアシネンシンと0.02%テアフラビンの両方を含む(IV)群では(I)群の約半分の値まで低下した。
これらのことから、テアシネンシン、テアフラビン、カテキン酸化重合体のいずれも単独で肝臓の中性脂肪を低下させる効果を有し、カテキン酸化重合体は単独で血清中性脂肪も低下させる効果を有する。
テアシネンシンとテアフラビンを同時に摂取すると、肝臓中性脂肪および血清中性脂肪の両方について、顕著な低下効果が得られることが明らかとなった。
From the results of Table 1, regarding serum triglyceride concentration, the KK-A y mice of the group (I) who took the control diet and the 0.03% theasinensin diet or the 0.02% theaflavin diet alone were ingested ( There was almost no difference between mice of group II) or group (III).
On the other hand, the serum triglyceride concentration of the mice in the (IV) group that received a diet containing both 0.03% theacinensin and 0.02% theaflavin was greatly reduced compared to the mice in the (I) group.
In addition, the KK-A y mice in the (V) group and the (VI) group that received a diet containing 0.1% or 0.5% catechin oxidation polymer were both compared to the mice in the (I) group. Serum triglyceride concentration decreased.
The liver triglyceride concentration is decreased in all groups as compared with the group (I), and the decrease in the groups (IV), (V), (VI) is particularly large. In the (IV) group containing both 0.02% theaflavins, the value dropped to about half that in the (I) group.
From these facts, theasinensin, theaflavin, and the catechin oxidation polymer all have the effect of reducing the neutral fat of the liver alone, and the catechin oxidation polymer alone has the effect of reducing the serum neutral fat.
It has been clarified that when theacinensin and theaflavin are taken at the same time, a remarkable lowering effect is obtained for both liver neutral fat and serum neutral fat.
<試験例2:体脂肪量および肝臓中性脂肪に対する効果>
試験例1で、テシネンシンとテアフラビンの同時摂取が、血清中性脂肪および肝臓中性脂肪の濃度を低下させる効果が大きいことが観察されたことから、次に、肥満を呈するラットに、テアシネンシンとテアフラビンを両方含む食餌を摂取させたときの、体脂肪量および肝臓中性脂肪濃度に及ぼす影響を調べた。
実験動物として、5週齢の肥満を呈する雄性のOtsuka Long−Evans Tokushima Fatty ラット(以下、OLETFラットという。)と、その対象モデル動物で肥満にならない正常の雄性のLong−Evans Tokushima Otsuka ラット(以下、LETO ラットという。)を用いた。
最初の3か月間はLETOおよびOLETFラットにMF固形飼料(オリエンタル酵母(株)製)を与えて予備飼育を行った。OLETFラットは5ヶ月齢頃から肥満の症状を呈することから、その1ヶ月前の4ヶ月齢からLETOラットと共に試験食の摂食を開始した。すなわち、4ヶ月齢の時に、OLETFラットを平均体重が同じになるように1群6匹ずつ合計2群に群分けした。その後、以下の試験食を5ヶ月間自由摂食させた。
(VII)群:LETO ラットに上記(I)群と同じコントロール食を試験食として摂取させた。
(VIII)群:OLLETFラットに上記(I)群と同じコントロール食を試験食として摂取させた。
(IX)群:OLLETFラットに上記(IV)群と同じ試験食を摂取させた。
いずれの群も飼育期間中、摂食量は毎日測定し、体重は1日おきに測定した。試験食の摂取を開始してから5ヶ月後の体脂肪量と肝臓の中性脂肪濃度を測定した。その結果を表2に示す。
<Test Example 2: Effect on body fat mass and liver neutral fat>
In Test Example 1, it was observed that the simultaneous intake of tesinensin and theaflavin had a large effect of reducing the concentrations of serum neutral fat and liver neutral fat. We examined the effects of diets containing both of these on body fat mass and liver neutral fat concentration.
As experimental animals, male Otsuka Long-Evans Tokyo Fatty rats (hereinafter referred to as OLETF rats) exhibiting 5-week-old obesity and normal male Long-Evans Tokyo Otsuka rats (hereinafter referred to as OLETF rats) that do not become obese in the target model animals. , Referred to as LETO rats).
During the first 3 months, MF chow (manufactured by Oriental Yeast Co., Ltd.) was given to LETO and OLETF rats for preliminary breeding. Since the OLETF rats exhibited symptoms of obesity at around 5 months of age, feeding of the test meal was started together with the LETO rats from 4 months of age one month before. That is, at the age of 4 months, the OLETF rats were divided into 2 groups, 6 animals per group so that the average body weight was the same. Thereafter, the following test meals were fed freely for 5 months.
(VII) group: LETO rats were fed the same control food as the above (I) group as a test food.
(VIII) group: The same control food as the above-mentioned (I) group was given to the OLETF rats as a test meal.
(IX) group: The OLETF rats were fed the same test meal as in the above (IV) group.
In each group, during the breeding period, the amount of food intake was measured every day, and the body weight was measured every other day. The body fat mass and the neutral fat concentration of the liver were measured 5 months after the start of the test food intake. The results are shown in Table 2.
なお、体脂肪量の測定は、飼育終了後解剖し、腎臓周辺および睾丸周辺脂肪組織を摘出し、重量を計測することにより行った。表2の値は各群の平均値である。 In addition, the body fat amount was measured by dissection after the breeding, removing the fat tissue around the kidney and the testicles, and measuring the weight. The values in Table 2 are average values for each group.
表2の結果より、肥満を呈するOLETFラットにおいて、0.03%のテアシネンシンと0.02%のテアフラビンの両方含む食餌を摂取した(IX)群は、(VIII)群のコントロール食を摂取したOLETFラットより体脂肪が少ない。
また、(VIII)群のコントロール食摂取OLETFラットの肝臓中性脂肪濃度は、(VII)群のコントロール食摂取LETOラットよりかなり高くなったが、(IX)群は(VIII)群に比べて著しく低い。
このことから、テアシネンシンとテアフラビンの同時摂取が肝臓中性脂肪濃度を低下させ、体脂肪の増加を抑えることが認められた。
From the results of Table 2, in the OLETF rats exhibiting obesity, the (IX) group that received a diet containing both 0.03% theacinensin and 0.02% theaflavin was the OLETF that received the control diet of the (VIII) group. Less body fat than rats.
Moreover, the liver triglyceride concentration of the OLETF rats fed with the control food in the (VIII) group was considerably higher than the LETO rats fed with the control food in the (VII) group, but the (IX) group was markedly higher than the (VIII) group. Low.
From this, it was recognized that simultaneous intake of theacinensin and theaflavin decreased the liver triglyceride concentration and suppressed the increase in body fat.
<試験例3:脂肪の吸収への影響>
製造例1で得られたテアシネンシン、テアフラビン、およびカテキン酸化重合体を用い、正常なラットの胃内にこれらの成分を投与した後、さらに胃内に油脂を投与したときの、腸管からの油脂の吸収に及ぼす影響を調べた。
(サンプル溶液の調製)
ラットの胃内に投与するサンプル溶液を調製した。ラットの体重1kgあたり20%エタノール溶液20mlをコントロール溶液とした。このコントロール溶液にラットの体重1kgあたり、テアシネンシン160mgとテアフラビン40mg(合計200mg)を同時に添加した溶液(以下、200mgSFという)、テアシネンシン800mgとテアフラビン200mg(合計1000mg)を同時に添加した溶液(以下、1000mgSFという)、200mgのカテキン酸化重合体を添加した溶液(以下、200mgBという。)、および1000mgのカテキン酸化重合体を添加した溶液(以下、1000mgBという)をそれぞれ調製した。
<Test Example 3: Effect on fat absorption>
Using the theacinensin, theaflavin, and the catechin oxidized polymer obtained in Production Example 1, after administering these components into the stomach of a normal rat, and further administering the fat into the stomach, the fat and oil from the intestinal tract The effect on absorption was investigated.
(Preparation of sample solution)
A sample solution to be administered into the rat stomach was prepared. 20 ml of 20% ethanol solution per 1 kg body weight of the rat was used as a control solution. A solution in which 160 mg of theasinensin and 40 mg of theaflavin (total 200 mg) are simultaneously added to this control solution per 1 kg of the body weight of the rat (hereinafter referred to as 200 mgSF), and a solution in which 800 mg of theacinensin and 200 mg of theaflavin (total 1000 mg) are simultaneously added (hereinafter referred to as 1000 mgSF). ), 200 mg of a catechin oxidized polymer (hereinafter referred to as 200 mgB) and 1000 mg of a catechin oxidized polymer (hereinafter referred to as 1000 mgB) were prepared.
実験動物として、4週齢の正常なSDラットを用い、室温22±1℃、湿度55±5%、8:00〜20:00点灯のライトサイクルの動物飼育室において、市販のMF固形飼料(オリエンタル酵母(株)製)を与えて飼育した。
1週間後、平均体重が同じになるように1群8匹ずつ合計5群に群分けし、以下の実験を行った。
初めに、6時間絶食したSDラットの尾静脈から血液を採取した。その後、上記のサンプル溶液をゾンデを用いて胃内に強制的に投与した。5分後、体重1kgあたり10mlのコーン油をゾンデを用いて胃内に強制的に投与した。その後、正確に1、2、4、6および8時間後にラットの尾静脈より採血した。各時間に採取した血液から血清を分離して中性脂肪濃度を測定することにより、油脂の腸管から血中への吸収の程度を調べた。
その結果を図6に示す。図6において、横軸はコーン油を投与してからの経過時間(単位:時間)を示し、縦軸は血清の中性脂肪濃度(単位:mg/dl)を示す。
As a laboratory animal, a normal SD rat at 4 weeks of age was used, and a commercially available MF chow (in a light cycle animal room with a room temperature of 22 ± 1 ° C., a humidity of 55 ± 5%, and a lighting cycle of 8: 00-20: 00, Oriental Yeast Co., Ltd.) was given and reared.
One week later, 8 animals were grouped into 5 groups in total so that the average body weights were the same, and the following experiment was performed.
First, blood was collected from the tail vein of SD rats fasted for 6 hours. Thereafter, the sample solution was forcibly administered into the stomach using a sonde. After 5 minutes, 10 ml of corn oil per kg of body weight was forcibly administered into the stomach using a sonde. Thereafter, blood was collected from the tail vein of rats exactly 1, 2, 4, 6 and 8 hours later. The degree of absorption of fat from the intestinal tract into the blood was examined by separating serum from blood collected at each time and measuring the neutral fat concentration.
The result is shown in FIG. In FIG. 6, the horizontal axis indicates the elapsed time (unit: time) after administration of corn oil, and the vertical axis indicates the neutral fat concentration (unit: mg / dl) of serum.
図6の結果より、コントロール溶液を投与した後にコーン油を投与したコントロール群の血清中性脂肪濃度は、投与後漸次上昇して4時間後に最大となり、その後低下したが、8時間後まで投与時(0時間後)より高いレベルで推移した。200mgSF溶液を投与した後にコーン油を投与した200mgSF群のラットの血清中性脂肪濃度は、すべての測定時でコントロール群より低かった。1000mgSF群では、血清中性脂肪濃度はほとんど上昇せず、コントロール群や200mgSF群より明らかに低かった。このことから、テアシネンシンとテアフラビンを同時に摂取すると、脂肪の吸収が極めて効果的に抑制されることが明らかとなった。
200mgB溶液を投与した後にコーン油を投与した200mgB群のラットの血清中性脂肪濃度は、すべての測定時でコントロール群より低く、1000mgB群ではさらに低い値を示した。このことから、カテキン酸化重合体が脂肪の吸収を効果的に抑制することが明らかとなった。
これらの結果から、テアシネンシン、テアフラビンおよびカテキン酸化重合体は腸管からの脂肪の吸収を抑制し、これによって体内に入る食事中の脂肪の量が低減され、その結果、血中または肝臓の中性脂肪濃度を減少させ、体脂肪の増加を抑制していると考えられる。
From the results shown in FIG. 6, the serum neutral fat concentration in the control group administered corn oil after administration of the control solution gradually increased after administration and became the maximum after 4 hours, and then decreased, but until 8 hours after administration, It changed at a higher level (after 0 hours). Serum triglyceride concentrations in rats in the 200 mg SF group administered with 200 mg SF solution followed by corn oil were lower than in the control group at all measurements. In the 1000 mg SF group, the serum triglyceride concentration hardly increased and was clearly lower than that in the control group and the 200 mg SF group. From this, it was clarified that the absorption of fat is extremely effectively suppressed when theacinensin and theaflavin are ingested simultaneously.
Serum triglyceride concentrations of rats in the 200 mg B group administered with 200 mg B solution followed by corn oil were lower than those in the control group at all measurements, and lower in the 1000 mg B group. From this, it became clear that the catechin oxidized polymer effectively suppresses the absorption of fat.
From these results, theasinensin, theaflavin and catechin oxidized polymers inhibit the absorption of fat from the intestinal tract, thereby reducing the amount of fat in the diet that enters the body, resulting in neutral fat in the blood or liver It is thought that the concentration is decreased and the increase in body fat is suppressed.
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JP2015504681A (en) * | 2012-01-19 | 2015-02-16 | ユニリーバー・ナームローゼ・ベンノートシヤープ | How to make tea products |
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