JP2002249491A - New polyvalent phenol polymer and usage of the same - Google Patents
New polyvalent phenol polymer and usage of the sameInfo
- Publication number
- JP2002249491A JP2002249491A JP2001044685A JP2001044685A JP2002249491A JP 2002249491 A JP2002249491 A JP 2002249491A JP 2001044685 A JP2001044685 A JP 2001044685A JP 2001044685 A JP2001044685 A JP 2001044685A JP 2002249491 A JP2002249491 A JP 2002249491A
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- Prior art keywords
- polyhydric phenol
- phenol polymer
- configuration
- buckwheat
- polymer
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- 0 OC(CC(O)=C1C(C2O)C(C(O)=CC(O)=C[C@@]([C@]3O)C(C(CC(O)=C4C*5)O)=C4O[C@@]5c(cc4)cc(O)c4O)=CO[C@@]3c(cc3)cc(O)c3O)C=C1OC2c(cc1O)ccc1O Chemical compound OC(CC(O)=C1C(C2O)C(C(O)=CC(O)=C[C@@]([C@]3O)C(C(CC(O)=C4C*5)O)=C4O[C@@]5c(cc4)cc(O)c4O)=CO[C@@]3c(cc3)cc(O)c3O)C=C1OC2c(cc1O)ccc1O 0.000 description 1
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- Fodder In General (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、新規な多価フェノ
ール（ポリフェノール）重合体及びその重合体を有効成
分として含有する医薬組成物に関する。より詳しくは、
カテキン及び／またはエピカテキンを構成単位とする新
規多価フェノール重合体、及びその多価フェノール重合
体を有効成分とする、生体の脂質過酸化抑制、スーパー
オキシドジスムターゼ（ＳＯＤ）活性上昇、脳機能改善
効果等を有する医薬組成物に関する。TECHNICAL FIELD The present invention relates to a novel polyhydric phenol (polyphenol) polymer and a pharmaceutical composition containing the polymer as an active ingredient. More specifically,
Novel polyhydric phenol polymer containing catechin and / or epicatechin as a constitutional unit, and suppressing lipid peroxidation, increasing superoxide dismutase (SOD) activity, and improving brain function in living organisms using the polyhydric phenol polymer as an active ingredient The present invention relates to a pharmaceutical composition having an effect and the like.
【０００２】[0002]
【従来の技術】高齢化社会に向い、痴呆症、アルツハイ
マ−症候群等の脳疾患患者の増加が危惧されている。脳
疾患に罹患していなくとも、モノ忘れが激しい、度忘れ
する、等は人々が日常経験する事象であり、これを脳疾
患の予兆と見る場合もある。脳疾患を始めとする各種疾
病の要因には、生体内で生成される活性酸素種が関与す
ると言われるが、疾病との関連は完全には解明されてお
らず、活性酸素種の生成を抑制、制御する技術も開発さ
れていない。脳疾患等の有効な予防、治療技術は、現状
では存在しないに等しいと言える。2. Description of the Related Art An increasing number of patients with brain diseases such as dementia and Alzheimer's syndrome have been concerned about the aging society. Even if a person does not have a brain disease, he forgets things frequently, forgets frequently, etc., is an event that people experience every day, and may be regarded as a sign of brain disease. It is said that reactive oxygen species generated in vivo are involved in the factors of various diseases including brain disease, but the relationship with the disease has not been completely elucidated, and the generation of reactive oxygen species is suppressed. No control technology has been developed. It can be said that effective prevention and treatment techniques for brain diseases and the like do not exist at present.
【０００３】一方、食品、特に植物性の食品に含まれる
天然の生理活性物質の作用を活かして生活習慣病等の疾
病の予防や治療を試みる方法への関心が近年高まってい
る。しかし、植物体成分による生理活性化作用は、植物
体のどのような成分が有効成分なのか未解明なまま利用
されているケースが多く、その作用を確実に実現した
り、新たな機能を探求する段階には至っていない場合が
多い。On the other hand, in recent years, there has been an increasing interest in methods for preventing or treating diseases such as lifestyle-related diseases by utilizing the action of natural physiologically active substances contained in foods, especially plant foods. However, the bioactivating effects of plant components are often used without clarifying what components of the plant are the active ingredients, and the effects are surely realized and new functions are explored. In many cases, the stage has not yet been reached.
【０００４】蕎麦についても高血圧症予防、中性脂肪低
下等の民間療法的効用が知られており、蕎麦種子がルチ
ン、ケルセチン等のフラボノイド類、プロアントシアニ
ジン等の多価フェノール類等を成分として含有すること
が着目されている。このうち、ルチン、ケルセチン等の
フラボノイド類については検討が進んでいる。しかし、
蕎麦含有多価フェノール類については、具体的にどのよ
うな構造の化合物が含まれ、それによりどのような生理
活性作用が発揮されるかについての検討は殆どなされて
いない。[0004] Soba is also known for its folk remedies, such as prevention of hypertension and lowering of triglyceride, and buckwheat seeds contain flavonoids such as rutin and quercetin and polyhydric phenols such as proanthocyanidin as components. It is noted that Among them, flavonoids such as rutin and quercetin are being studied. But,
Regarding the buckwheat-containing polyhydric phenols, there has been hardly any study on the specific structure of the compound contained therein and what kind of bioactive effect is exhibited thereby.
【０００５】本発明者らは従来より蕎麦に着目して研究
を続け、既に蕎麦殻より抽出したエキスあるいはその分
画物を有効成分とする過酸化脂質抑制剤、コレステロ−
ル低下剤、中性脂肪低下剤及び高脂血症改善剤（特開平
10-218786号）、蕎麦種子、蕎麦種子の抽出物または蕎
麦種子抽出物の分画物を含有する老化の予防及び／また
は治療用組成物（特開2000-53575号）を提案している
が、その有効成分の具体的構造の解明には至っていな
い。The inventors of the present invention have continued their research with a focus on buckwheat, and have studied a cholesterol inhibitor, a lipid peroxide inhibitor containing an extract or a fraction thereof extracted from buckwheat husk as an active ingredient.
Drug, triglyceride lowering agent and hyperlipidemia improving agent
No. 10-218786), a composition for preventing and / or treating aging (JP-A-2000-53575), comprising buckwheat seed, buckwheat seed extract or a fraction of buckwheat seed extract. However, the specific structure of the active ingredient has not been elucidated.
【０００６】[0006]
【発明が解決しようとする課題】したがって、本発明は
蕎麦種子に含まれる生理活性を示す成分を分離同定し、
その生理活性作用を把握して医薬品等への利用を図るこ
とを目的とするものである。SUMMARY OF THE INVENTION Accordingly, the present invention separates and identifies a component having a physiological activity contained in buckwheat seed,
The purpose of the present invention is to grasp the physiological activity and use it in pharmaceuticals and the like.
【０００７】[0007]
【課題解決の手段】本発明者らは、蕎麦種子の抽出物に
含まれる多種多様な成分から生理活性成分を探索し、カ
テキン及びエピカテキンを構成単位とする生理活性作用
を有する新規な多価フェノール重合体が、生体の脂質過
酸化抑制、ＳＯＤ活性低下、脳機能改善等の効果を有す
ることを見出し、本発明を完成した。DISCLOSURE OF THE INVENTION The present inventors have searched for a physiologically active component from a variety of components contained in an extract of buckwheat seeds, and have developed a novel polyvalent compound having a physiologically active action comprising catechin and epicatechin as constituent units. The inventors have found that a phenolic polymer has effects such as suppression of lipid peroxidation in living organisms, reduction of SOD activity, improvement of brain function, and the like, and completed the present invention.
【０００８】すなわち、本発明は以下の新規な多価フェ
ノール重合体、これを含有する生理活性物質及び前記多
価フェノール重合体を有効成分とする医薬組成物を提供
する。 １．式（Ｉ）That is, the present invention provides the following novel polyhydric phenol polymer, a physiologically active substance containing the same, and a pharmaceutical composition containing the polyhydric phenol polymer as an active ingredient. 1. Formula (I)
【化３】 （式中、クロマン環の３位の水酸基の立体配置は、α配
置、β配置またはそれらの混合物を表わし、ｎは０また
は１以上の整数である。）で示される多価フェノール重
合体。 ２．式（Ｉ）で示される多価フェノール重合体における
各クロマン環の３位の水酸基の立体配置を、式（II）Embedded image (Wherein the configuration of the hydroxyl group at the 3-position of the chroman ring represents an α-configuration, a β-configuration or a mixture thereof, and n is 0 or an integer of 1 or more). 2. The configuration of the hydroxyl group at the 3-position of each chroman ring in the polyhydric phenol polymer represented by the formula (I) is represented by the formula (II)
【化４】 （式中、ｎは前記に同じ。）のＸ1及びＸ2で表わしたと
き、Ｘ1のα配置／β配置比が約２であり、Ｘ2のα配置
／β配置比が約0.5である前項１記載の多価フェノール
重合体。 ３．ｎが０または１〜７の整数である前項または２記載
の多価フェノール重合体。 ４．蕎麦抽出物から得られる前項１乃至３のいずれかに
記載の多価フェノール重合体。 ５．生理活性作用を有する前項１乃至４のいずれかに記
載の多価フェノール重合体。 ６．生理活性作用が脂質過酸化抑制作用である前項５に
記載の多価フェノール重合体。 ７．生理活性作用がスーパーオキシドジスムターゼ（Ｓ
ＯＤ）活性上昇作用である前項５に記載の多価フェノー
ル重合体。 ８．前項５に記載の多価フェノール重合体を有効成分と
する医薬組成物。 ９．脳機能改善作用を有する前項８に記載の医薬組成
物。 １０．脂質過酸化抑制作用及び／またはＳＯＤ活性上昇
作用を有する前項８に記載の医薬組成物。Embedded image (Wherein, n same. Above) when expressed by X 1 and X 2 of, alpha placement / beta arrangement ratio X 1 is about 2, alpha arrangement / beta arrangement ratio of X 2 of about 0.5 2. The polyhydric phenol polymer according to the above item 1. 3. 3. The polyhydric phenol polymer according to the above item or 2, wherein n is 0 or an integer of 1 to 7. 4. 4. The polyhydric phenol polymer according to any one of the above items 1 to 3, which is obtained from a buckwheat extract. 5. 5. The polyhydric phenol polymer according to any one of the above items 1 to 4, which has a physiological activity. 6. 6. The polyhydric phenol polymer according to the above item 5, wherein the physiologically active action is a lipid peroxidation inhibitory action. 7. Superoxide dismutase (S
OD) The polyhydric phenol polymer according to the above item 5, which has an activity increasing effect. 8. 6. A pharmaceutical composition comprising the polyhydric phenol polymer according to item 5 as an active ingredient. 9. 9. The pharmaceutical composition according to item 8, which has a cerebral function improving effect. 10. 9. The pharmaceutical composition according to the above item 8, which has a lipid peroxidation inhibitory effect and / or an SOD activity increasing effect.
【０００９】[0009]
【発明の実施の態様】以下、本発明を詳細に説明する。 （Ａ）多価フェノール重合体 本発明の新規多価フェノール重合体は、蕎麦抽出物に含
まれる生理活性作用を有する物質であり、下記式（Ｉ）
で示される基本構造を有する。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. (A) Polyhydric phenol polymer The novel polyhydric phenol polymer of the present invention is a substance having a physiological activity contained in buckwheat extract, and has the following formula (I)
Has a basic structure represented by
【化５】 Embedded image
【００１０】式中、クロマン環の３位の水酸基の結合を
示す波線は、In the formula, the wavy line indicating the bond of the hydroxyl group at the 3-position of the chroman ring is as follows:
【化６】 すなわち、紙面の手前側に結合しているβ配置を表わす
か、Embedded image In other words, it represents the β arrangement connected to the near side of the paper,
【化７】 すなわち、紙面の向う側に結合しているα配置を表わす
か、またはそれらの混合物を表わし、ｎは０または１以
上の整数である。式（Ｉ）中のベンゼン環及びクロマン
環は水酸基、アルコキシル基、アシル基、Ｏ−グリコシ
ル基、及びＣ−グリコシル基等の置換基で修飾されてい
てもよい。Embedded image That is, n represents 0 or an integer of 1 or more, which represents the α configuration bonded to the other side of the paper surface or a mixture thereof. The benzene ring and the chroman ring in the formula (I) may be modified with a substituent such as a hydroxyl group, an alkoxyl group, an acyl group, an O-glycosyl group, and a C-glycosyl group.
【００１１】後述の実施例により蕎麦抽出液から得られ
た式（Ｉ）で示される本発明の多価フェノール重合体の
具体例では、式（Ｉ）を下記式（II）In a specific example of the polyhydric phenol polymer of the present invention represented by the formula (I) obtained from buckwheat extract according to the examples described below, the formula (I) is replaced by the following formula (II)
【化８】 （式中、ｎは前記に同じ。）で表わした場合において、
Ｘ1ではα配置／β配置比が約２（1.75〜2.25）であ
り、Ｘ2ではα配置／β配置比が約0.5（0.4〜0.6）であ
ったが、本発明化合物のＸ1及びＸ2のα配置／β配置の
比はこの範囲に限定されるものではない。Embedded image (Where n is the same as above)
X In 1 alpha arranged / beta arrangement ratio of about 2 (1.75 to 2.25), but the X 2 alpha arranged / beta disposed ratio of about 0.5 (0.4 to 0.6), X 1 and X of the present invention compounds The ratio of α configuration / β configuration of 2 is not limited to this range.
【００１２】式（Ｉ）の基本単位化合物であるＸ1がα
配置の化合物：X 1 which is a basic unit compound of the formula (I) is α
Configuration of compounds:
【化９】 はエピカテキン(epicatechin)として知られ、Ｘ1がβ配
置の化合物：Embedded image Is known as epicatechin, wherein X 1 is in the β configuration:
【化１０】 はカテキン(catechin)として知られている化合物であ
り、本発明の多価フェノール重合体はカテキン−エピカ
テキン重合体である。Embedded image Is a compound known as catechin, and the polyhydric phenol polymer of the present invention is a catechin-epicatechin polymer.
【００１３】蕎麦抽出物から得られる本発明のカテキン
−エピカテキン重合体の中でも、２量体（式（Ｉ）でｎ
＝０）から９量体（式（Ｉ）でｎ＝７）の範囲のものに
優れた生理活性作用が認められた。Among the catechin-epicatechin polymers of the present invention obtained from buckwheat extract, dimers (n in the formula (I))
= 0) to 9-mers (n = 7 in the formula (I)) exhibited excellent bioactive effects.
【００１４】（Ｂ）製造方法 上記の多価フェノール重合体は蕎麦、特に蕎麦種子から
抽出分離して得ることができる。蕎麦種子は薄膜で被覆
された子実、すなわち蕎麦粉を採取する部分の外側を、
蕎麦殻と呼ばれる表皮で覆った構造からなるが、本発明
では、このような構造の種子全体、あるいはその一部
（子実、薄膜、あるいは殻等）を指し、必要によりこれ
らを単独で、あるいは２種以上を併用する。蕎麦種子そ
れ自体または必要により適宜粉末化したもの、あるいは
蕎麦種子を水、アルコールその他の溶媒で抽出して得た
エキス、あるいはこのエキスを更に適宜の手段により分
画、精製して得た特定の画分が利用できる。(B) Production Method The above polyhydric phenol polymer can be obtained by extraction and separation from buckwheat, especially buckwheat seeds. The buckwheat seeds are covered with a thin film of grain, that is, the outside of the part where the buckwheat flour is collected.
It consists of a structure covered with a so-called buckwheat hull. In the present invention, it refers to the whole seed or such a part (grain, thin film, shell, etc.), and if necessary, these alone or Use two or more types together. Buckwheat seeds themselves or those appropriately powdered as necessary, or extracts obtained by extracting buckwheat seeds with water, alcohol or other solvents, or specific extracts obtained by further fractionating and purifying this extract by appropriate means Fractions are available.
【００１５】蕎麦種子それ自体を用いる場合は、適宜粉
砕、篩別等の処理を施した粉末として用いる。粉砕、篩
別処理の前後には、必要により加熱、加圧その他の物理
的処理を行ってもよい。粉砕、篩別その他の処理には、
通常一般的に使用される機器類を、通常の条件で使用す
ればよい。When the buckwheat seed itself is used, it is used as a powder which has been appropriately subjected to treatment such as pulverization and sieving. Before and after the pulverizing and sieving treatments, if necessary, heating, pressurizing and other physical treatments may be performed. For crushing, sieving and other processing,
Normally used devices may be used under normal conditions.
【００１６】蕎麦種子からのエキス抽出に用いる溶媒と
しては、通常、水系溶媒（水、または酸、塩、塩基、ア
ルコール等の水溶液）、有機溶媒、あるいはこれらの混
合物が用いられる。エキス抽出は常圧または加圧下で、
常温ないし６０℃程度で１〜３時間程度行われるが、必
要により７０〜１５０℃程度としてもよく、時間も１時
間以下に短縮、あるいは３〜５時間程度に延長してもよ
い。いずれの条件でも所要の品質の抽出エキスの回収が
可能であり、抽出条件は作業性や経済性等を考慮して適
宜選択すればよい。抽出処理後、ろ過、遠心分離等適宜
の手段で抽出液を回収し、必要により溶媒除去、エキス
分の濃縮、乾燥、粉末化等の処理を行う。濃縮エキスの
乾燥、粉末化に際し、適宜の賦形剤を使用してもよい。As the solvent used for extracting the extract from buckwheat seed, an aqueous solvent (water or an aqueous solution of an acid, salt, base, alcohol, or the like), an organic solvent, or a mixture thereof is usually used. Extract extraction at normal pressure or under pressure,
The reaction is carried out at room temperature to about 60 ° C. for about 1 to 3 hours, but may be performed at about 70 to 150 ° C. if necessary, and the time may be shortened to 1 hour or less or extended to about 3 to 5 hours. Under any of the conditions, the extract of the required quality can be recovered, and the extraction conditions may be appropriately selected in consideration of workability, economy, and the like. After the extraction treatment, the extract is collected by an appropriate means such as filtration and centrifugation, and if necessary, the solvent is removed, the extract is concentrated, dried, and powdered. In drying and powdering the concentrated extract, an appropriate excipient may be used.
【００１７】蕎麦種子の抽出エキスを、限外ろ過、逆浸
透等の膜処理、または各種クロマトグラフィー処理する
ことにより、目的とする活性画分が得られる。吸着剤と
しては、スチレン・ジビニルベンゼン系やメタクリル酸
系等の吸着剤、親水性ビニルポリマー、修飾デキストラ
ンゲル、ポリアクリルアミドゲル、逆相系シリカゲル、
イオン交換樹脂等が用いられる。吸着画分は、含水アル
コール、アルコール、アセトン等で溶出して回収され
る。画分の主成分は多価フェノール化合物である。The target active fraction can be obtained by subjecting the buckwheat seed extract to a membrane treatment such as ultrafiltration or reverse osmosis, or various chromatographic treatments. As the adsorbent, adsorbents such as styrene / divinylbenzene type and methacrylic acid type, hydrophilic vinyl polymer, modified dextran gel, polyacrylamide gel, reverse phase silica gel,
An ion exchange resin or the like is used. The adsorbed fraction is recovered by elution with aqueous alcohol, alcohol, acetone or the like. The main component of the fraction is a polyhydric phenol compound.
【００１８】（Ｃ）生理活性作用及び用途 本発明の多価フェノール重合体は、分画した各分画成分
でも、また混合物〔式（Ｉ）のでｎ＝０〜７の混合物〕
でも血中の過酸化脂質の低下、ＳＯＤ（スーパーオキシ
ドジスムターゼ）活性の上昇等の効果を有する。(C) Physiological activity and use The polyhydric phenol polymer of the present invention can be obtained by fractionating each fraction component or a mixture (a mixture of n = 0 to 7 in the formula (I)).
However, it has effects such as a decrease in blood lipid peroxide and an increase in SOD (superoxide dismutase) activity.
【００１９】本発明の多価フェノール重合体による生理
活性作用としては、脳機能改善効果が挙げられる。脳機
能改善効果の例としては、痴呆症やアルツハイマー症候
群等の脳の病的障害を予防・治療・改善する効果、学習
能力、記憶・思考能力、言語・時空間・抽象的事象等を
認知、弁別する能力等、脳の活動機能の活性化・向上作
用が含まれる。また、ここに挙げた知的作用の改善と同
時に、イライラ感の減少、不眠の解消、落着き回復その
他、脳機能の不調に関連すると考えられる諸状態につい
ての改善効果も含まれる。本発明の多価フェノール重合
体による脳機能改善効果については、例えば、脳中のプ
ロテインキナーゼＣ（ＰＫＣ）の活性向上作用等が関与
していると考えられる。The physiologically active action of the polyhydric phenol polymer of the present invention includes a brain function improving effect. Examples of brain function improvement effects include the effects of preventing, treating and improving pathological disorders of the brain such as dementia and Alzheimer's syndrome, learning ability, memory and thinking ability, recognizing language, spatiotemporal and abstract events, etc. Includes activation and enhancement of brain activity functions, such as the ability to discriminate. In addition to the improvement of the intellectual effects mentioned above, the effects include reduction of irritability, elimination of insomnia, restoring calmness, and other conditions considered to be related to dysfunction of brain function. The effect of the polyhydric phenol polymer of the present invention to improve brain function is considered to involve, for example, the activity of improving the activity of protein kinase C (PKC) in the brain.
【００２０】また、本発明の多価フェノール重合体は、
活性酸素種により生じる生体内物質の酸化的変性を抑え
るため、酸化脂質の生成抑制、ＳＯＤ活性の上昇等の効
果が含まれる。従って、生体内での過酸化脂質の生成が
引金となると考えられる高脂血症や糖尿病等を改善し、
中性脂肪やコレステロール等を低下させる効果をも有す
る。Further, the polyhydric phenol polymer of the present invention comprises:
In order to suppress the oxidative denaturation of the substance in the living body caused by the reactive oxygen species, effects such as suppression of the production of oxidized lipids and an increase in SOD activity are included. Therefore, to improve hyperlipidemia, diabetes, etc., which is considered to be triggered by the production of lipid peroxide in vivo,
It also has the effect of lowering neutral fats and cholesterol.
【００２１】本発明の多価フェノール重合体は上記の効
果を有する一方、慢性毒性も急性毒性も全く認めらな
い。従って、これを食品や飲料の添加物として用いたり
医薬組成物として用いることが可能である。また、化粧
品中の脂質の酸化を抑えこれを安定化したり、飼料等に
添加することも可能である。医薬組成物として用いる場
合の構成は任意であり、経口または非経口で用いられ
る。投与量は年齢、体重、症状、目的の治療効果、投与
方法等により広い範囲で用いることができる。経口的使
用の場合は、例えば、成人一人あたり一回につき、１ｍ
ｇ〜１ｇ程度が適当である。一般に、錠剤、丸剤、カプ
セル剤、散剤、顆粒剤、シロップ剤等の形で投与される
が、必要により注射剤、塗布剤等で用いる場合もある。
更に、造粒、錠剤化あるいはシロップ剤、塗布剤等調製
の際、必要により適宜の補助資材（澱粉類、デキストリ
ン、甘味料類、色素、香料等）を使用することもでき
る。While the polyhydric phenol polymer of the present invention has the above-mentioned effects, it has no chronic toxicity or acute toxicity. Therefore, it can be used as an additive in foods and beverages or as a pharmaceutical composition. It is also possible to suppress the oxidation of lipids in cosmetics to stabilize them, or to add them to feeds and the like. The composition for use as a pharmaceutical composition is arbitrary, and is used orally or parenterally. The dose can be used in a wide range depending on age, body weight, symptoms, intended therapeutic effect, administration method, and the like. In the case of oral use, for example, 1 m per adult
g to 1 g is appropriate. Generally, they are administered in the form of tablets, pills, capsules, powders, granules, syrups and the like, but they may be used in injections, liniments and the like, if necessary.
Further, when granulating, tableting or preparing syrups, coatings and the like, appropriate auxiliary materials (starches, dextrins, sweeteners, pigments, flavors, etc.) can be used as necessary.
【００２２】[0022]
【実施例】実施例１ 本発明者らは、蕎麦種子の水抽出物から得た５０％アセ
トン画分が生理活性作用を示すことを確認しているが
（特開2000-53575号）、これをさらにセファデックスＬ
Ｈ−２０により、（ａ）分子量が約５００以下の画分、
（ｂ）分子量が約５００以上の画分に分画し、それぞれ
について老化促進マウス（ＳＡＭ）を用いた試験により
有効成分が後者に含有されていることを示す結果を得た
が、その有効成分の構造を以下の方法により検討した。EXAMPLES Example 1 The present inventors have confirmed that a 50% acetone fraction obtained from an aqueous extract of buckwheat seed has a bioactive effect (Japanese Patent Laid-Open No. 2000-53575). And Sephadex L
By H-20, (a) a fraction having a molecular weight of about 500 or less,
(B) fractionation into fractions having a molecular weight of about 500 or more, and a test using each of the aging-promoting mice (SAM) showed that the active ingredient was contained in the latter. Was studied by the following method.
【００２３】（１）蕎麦抽出成分の分画 夾雑物を除去した蕎麦全粒種子（北海道産）を水洗、乾
燥した後、全体を４０メッシュ以下に粉砕し、篩別した
粉末１ｋｇに水２０リットルを加え、加圧下で１２０
℃、１時間撹拌抽出処理して得た抽出液５０ｇを、水、
及び水−アセトン（アセトン５０％）を用いてＭＣＩゲ
ル（三菱化学（株））により分離し、水で平衡化したセ
ファデックスＬＨ−２０（ファルマシア製、修飾デキス
トランゲル）に吸着させ、水、メタノール画分、５０％
アセトン画分に分画した。メタノール画分（6.6ｇ）
は、更にエタノールで平衡化したセファデックスＬＨ−
２０（ファルマシア製、修飾デキストランゲル）に吸着
させ、エタノール、水−エタノール（エタノール８０
％、エタノール７０％、エタノール６０％）及び、水−
アセトン（アセトン５０％）を用いて５画分に分画し
た。(1) Fractionation of buckwheat extract components Whole buckwheat seeds (from Hokkaido) from which contaminants have been removed are washed with water and dried, and the whole is ground to 40 mesh or less, and 20 liters of water is added to 1 kg of sieved powder 1 kg. And pressurized to 120
50 g of the extract obtained by stirring and extracting for 1 hour at a temperature of
And Sephadex LH-20 (Pharmacia, modified dextran gel) equilibrated with water, separated by MCI gel (Mitsubishi Chemical Corporation) using water-acetone (acetone 50%), and mixed with water, methanol Fraction, 50%
It was fractionated into an acetone fraction. Methanol fraction (6.6 g)
Is Sephadex LH-
20 (manufactured by Pharmacia, modified dextran gel), and ethanol, water-ethanol (ethanol 80
%, Ethanol 70%, ethanol 60%) and water-
It was fractionated into 5 fractions using acetone (acetone 50%).
【００２４】得られた画分は、次のとおりである（括弧
内は溶離溶媒留去後の乾燥物の残存量）。 エタノール画分（0.71ｇ） ８０％エタノール画分（1.19ｇ） ７０％エタノール画分（1.99ｇ） ６０％エタノール画分（1.29ｇ） ５０％アセトン画分（エタノール平衡化セファデック
スＬＨ−２０）（1.41ｇ） ５０％アセトン画分（水平衡化セファデックスＬＨ−
２０）（3.3ｇ）The obtained fractions are as follows (the values in parentheses indicate the remaining amount of the dried product after the elution of the elution solvent). Ethanol fraction (0.71 g) 80% ethanol fraction (1.19 g) 70% ethanol fraction (1.99 g) 60% ethanol fraction (1.29 g) 50% acetone fraction (Sephadex LH-20 equilibrated with ethanol) ( 1.41 g) 50% acetone fraction (Sephadex LH-
20) (3.3g)
【００２５】（２）蕎麦抽出成分の構造解析 チオリシス法（Y.Kashiwada, et al., Chem Pharm. Bul
l. 38(4) 856-860 (1990)）により、各画分中の多価フ
ェノールの単位構造、重合度等を調べた。この方法の基
本原理を次式に示す。(2) Structural analysis of buckwheat extract components Thiolysis method (Y. Kashiwada, et al., Chem Pharm. Bul
l. 38 (4) 856-860 (1990)), the unit structure of polyhydric phenol in each fraction, the degree of polymerization and the like were examined. The following shows the basic principle of this method.
【化１１】 フェノール（単位構造）のｎ量体を酸（酢酸または塩
酸）、ベンジルメルカプタン（Ｐｈ−ＣＨ2−ＳＨ）の
存在下で加熱還流すると式中点線で示した結合部位が切
断され、（ｎ−１）個のベンジルチオエーテル結合ユニ
ット（チオエーテル体）と、１個の末端の多価フェノー
ル（単位構造）が生成する。チオリシスによる反応生成
物を回収してその構造を分析することにより、多価フェ
ノールの単位構造が、またチオエーテル体と非チオエー
テル体の収量の比から重合度が明らかになる。Embedded image When the n-mer of phenol (unit structure) is heated under reflux in the presence of an acid (acetic acid or hydrochloric acid) and benzyl mercaptan (Ph-CH 2 -SH), the binding site shown by the dotted line in the formula is cleaved, and (n-1) ) Benzylthioether binding units (thioethers) and one terminal polyhydric phenol (unit structure) are produced. By recovering the reaction product by thiolysis and analyzing the structure, the unit structure of the polyhydric phenol and the degree of polymerization can be determined from the yield ratio between the thioether compound and the non-thioether compound.
【００２６】前記（１）でた６画分〜について各試
料１００ｍｇをそれぞれエタノール１０ｍＬに溶解し、
これらの試料溶液それぞれに酢酸３ｍＬ、ベンジルメル
カプタン２ｍＬを滴下して窒素気流下９５℃で撹拌しな
がら還流した。一定時間ごとに反応混合液の一部を取出
し、ＨＰＬＣで分析して反応の終結を確認した。ＨＰＬ
Ｃ条件は、次のとおりである。For each of the 6 fractions of (1) above, 100 mg of each sample was dissolved in 10 mL of ethanol.
3 mL of acetic acid and 2 mL of benzyl mercaptan were added dropwise to each of these sample solutions, and the mixture was refluxed with stirring at 95 ° C. under a nitrogen stream. A portion of the reaction mixture was removed at regular intervals and analyzed by HPLC to confirm the completion of the reaction. HPL
The condition C is as follows.
【００２７】カラム：ＴＳＫゲルＯＤＳ−８０Ｔｓ（4.
6ｍｍ径×１５ｃｍ、東ソー製） 条件： ０〜５分 Ｂ １０％ ５→２５分 Ｂ １０％→９０％ ２５〜３０分 Ｂ ９０％ 流速：0.8ｍＬ／ｍｉｎ 検出：２６０ｎｍColumn: TSK gel ODS-80Ts (4.
6mm diameter x 15cm, manufactured by Tosoh) Conditions: 0 to 5 minutes B 10% 5 → 25 minutes B 10% → 90% 25 to 30 minutes B 90% Flow rate: 0.8 mL / min Detection: 260 nm
【００２８】チオリシス反応終了時点のＨＰＬＣチャー
トを図１（６０％エタノール画分のもの）に示す。図
中、保持時間9.48分及び12.55分のピーク成分は、標準
品との対比からそれぞれカテキン、及びエピカテキン
（ピーク比が約２：１）であることが確認された。The HPLC chart at the end of the thiolysis reaction is shown in FIG. 1 (60% ethanol fraction). In the figure, it was confirmed that the peak components at a retention time of 9.48 minutes and 12.55 minutes were catechin and epicatechin (peak ratio: about 2: 1), respectively, in comparison with the standard product.
【００２９】また、ベンジルチオエーテル結合ユニット
（チオエーテル体）について、同様に構造を確認したと
ころ、カテキン及びエピカテキンのベンジルチオエーテ
ル結合ユニットの含有比は約１：２であることが確認さ
れた。この結果から、蕎麦由来の多価フェノール重合体
はカテキン、及びエピカテキンを構成単位とする重合体
であることが判明した。なお、保持時間14.62分のピー
クは、開環体等の副生成物と考えられる。また、これら
のピークとベンジルチオエーテル結合ユニット（チオエ
ーテル体）である保持時間18.83分のピークの面積比か
ら、下記式に従って平均重合度を算出した。The structure of the benzyl thioether binding unit (thioether) was confirmed in the same manner, and it was confirmed that the content ratio of the benzyl thioether binding unit of catechin and epicatechin was about 1: 2. From this result, it was found that the buckwheat-derived polyhydric phenol polymer was a polymer having catechin and epicatechin as constituent units. The peak at a retention time of 14.62 minutes is considered to be a by-product such as a ring-opened product. The average degree of polymerization was calculated from the area ratio between these peaks and the peak having a retention time of 18.83 minutes as a benzyl thioether binding unit (thioether compound) according to the following formula.
【数１】 式中の記号は以下の意味を表わす。 ＡT：チオエーテル化合物ピーク面積 ＩT：チオエーテル化合物のモル吸光係数 ＡC：カテキンピーク面積 ＩC：カテキンのモル吸光係数 ＡE：エピカテキンピーク面積 ＩE：エピカテキンのモル吸光係数(Equation 1) The symbols in the formula have the following meanings. A T: thioether compounds peak area I T: molar extinction coefficient of thioether compounds A C: catechin peak area I C: catechin molar absorption coefficient A E: epicatechin peak area I E: molar extinction coefficient of epicatechin
【００３０】その結果、各画分の平均重合度は以下のと
おりであった。 エタノール画分：単純多価フェノール（重合してない
カテキン、ルチン等） ８０％エタノール画分：平均重合度３のカテキン・エ
ピカテキン重合体 ７０％エタノ−ル画分：平均重合度５のカテキン・エ
ピカテキン重合体 ６０％エタノール画分：平均重合度７のカテキン・エ
ピカテキン重合体 ５０％アセトン画分 ：平均重合度８のカテキン・エ
ピカテキン重合体 ５０％アセトン画分 ：平均重合度９のカテキン・エ
ピカテキン重合体 以上の結果から、重要な効果を有する多価フェノール重
合体は下記の基本構造で示されるカテキンとエピカテキ
ンを構成単位とするポリマーないしオリゴマーであると
考えられる。As a result, the average polymerization degree of each fraction was as follows. Ethanol fraction: simple polyhydric phenol (non-polymerized catechin, rutin, etc.) 80% ethanol fraction: catechin / epicatechin polymer having an average degree of polymerization of 3 70% ethanol fraction: catechin having an average degree of polymerization of 5 Epicatechin polymer 60% ethanol fraction: catechin / epicatechin polymer with an average degree of polymerization of 50 50% acetone fraction: catechin / epicatechin polymer with an average degree of polymerization of 8 50% acetone fraction: catechin with an average degree of polymerization of 9 -Epicatechin polymer From the above results, it is considered that a polyhydric phenol polymer having an important effect is a polymer or oligomer having catechin and epicatechin represented by the following basic structures as constituent units.
【化１２】 Embedded image
【００３１】（３）構造と活性の相関 リノール酸の自動酸化阻害作用に関するPrattらの方法
（Natural antioxidants from plant material. In Phe
nolic Compounds in Food and their effect onHealth
II：Antioxidants and Cancer Prevention:Huang, M-T,
Ho, C-T., Lee,C.Y., Eds.;American Chemical Societ
y: Washington, DC, 1992; pp54-71)に従って測定し
た。(3) Correlation between Structure and Activity Pratt et al.'S method (Natural antioxidants from plant material. In Phe
nolic Compounds in Food and their effect onHealth
II: Antioxidants and Cancer Prevention: Huang, MT,
Ho, CT., Lee, CY, Eds .; American Chemical Societ
y: Washington, DC, 1992; pp54-71).
【００３２】リノール酸２０ｍｇ及びトゥイーン２０
（Tween 20）を２００ｍｇを秤量して遮光三角フラスコ
に入れ、これに0.2ｍｇ／ｍＬのβ−カロチン・クロロ
ホルム溶液１ｍＬを加えて窒素ガスを吹込みながら濃縮
した。これに(i)〜の画分のそれぞれの乾燥試料を
５００μｇ／ｍＬの濃度となるように蒸留水に溶解して
得た試料１ｍＬ、及び(ii)0.5Ｌ／ｍｉｎの割合で１時
間空気を送り込んで調製した５０ｍＬの空気飽和蒸留水
を加えて混合し、５０℃でインキュベートした。Linoleic acid 20 mg and Tween 20
200 mg of (Tween 20) was weighed and placed in a light-shielded Erlenmeyer flask, and 1 mL of a 0.2 mg / mL β-carotene / chloroform solution was added thereto, followed by concentration while blowing in nitrogen gas. 1 mL of a sample obtained by dissolving each dried sample of the fractions (i) to (5) in distilled water to a concentration of 500 μg / mL, and (ii) air for 1 hour at a rate of 0.5 L / min. 50 mL of air-saturated distilled water prepared by feeding was added, mixed, and incubated at 50 ° C.
【００３３】その後、β−カロチンの退色を観察するた
め、３０分後及び９０分後に上記試験液を取出し、その
吸光度（４７０ｎｍ）を測定し、阻害活性（抗脂質過酸
化活性）を次式により求めた。Thereafter, in order to observe the fading of β-carotene, the test solution was taken out after 30 minutes and 90 minutes, the absorbance (470 nm) was measured, and the inhibitory activity (anti-lipid peroxidation activity) was calculated by the following formula. I asked.
【数２】 式中、退色比は３０分後の吸光度(a)と９０分後の吸光
度(b)との比の自然対数値（ｌｎ（ａ／ｂ））である。(Equation 2) In the formula, the fading ratio is the natural logarithm (ln (a / b)) of the ratio of the absorbance after 30 minutes (a) to the absorbance after 90 minutes (b).
【００３４】結果を図２に示す。図中の破線は分画処理
を経ていない蕎麦抽出液の活性値であり、図に示すよう
に本発明の蕎麦抽出液の主成分と考えられるカテキン・
エピカテキン重合体では平均重合度３〜７で強い活性を
示すことが明らかである。抗酸化活性が水酸基の数に依
存するのであれば、質量基準で比較する限り単量体でも
重合体でも結果は同じになる筈であるが、重合体の方が
活性が高いという結果は、単量体分子が数多く含まれて
いるより、これらが重合していることが重要であること
を示すものである。FIG. 2 shows the results. The dashed line in the figure indicates the activity value of the buckwheat extract that has not been subjected to the fractionation treatment.
It is clear that the epicatechin polymer exhibits strong activity at an average degree of polymerization of 3 to 7. If the antioxidant activity is dependent on the number of hydroxyl groups, the results should be the same for both monomer and polymer as far as they are compared on a mass basis. This indicates that it is more important that these molecules are polymerized than a large number of monomer molecules are contained.
【００３５】実施例２：多価フェノール重合体の生理活
性効果のin vivo確認試験 実施例１記載の方法に従って蕎麦種子抽出液から調製し
た、低分子多価フェノール（平均重合度４）、高分子多
価フェノール（平均重合度８）を試料として、マウスに
対するin vivoの活性を調べた。Example 2 In Vivo Confirmation Test of Physiological Activity Effect of Polyhydric Phenol Polymer Low-molecular-weight polyhydric phenol (average degree of polymerization: 4), polymer prepared from buckwheat seed extract according to the method described in Example 1. Using polyhydric phenol (average degree of polymerization 8) as a sample, the in vivo activity on mice was examined.
【００３６】生後７週齢、雄性のＩＣＲマウスを１群６
〜７匹とし、0.75％の鉄粉（和光純薬）を配合した標準
飼料（ＣＥ−２）を４週間投与して脂質過酸化モデルを
作成した。試料投与群には鉄配合飼料に試料0.75％を添
加して投与し、飼料と水は自由摂取とした。解剖時に血
液を採取し、血液から血清を分離した。市販のキット
（ＳＯＤテストワコー、ＬＰＯテストワコー）を用いて
抗酸化指標を測定した。結果を図３に示す。図中、ＳＯ
Ｄはスーパーオキシドジスムターゼ活性であり、ＬＰＯ
は過酸化脂質であり、低分子及び高分子は、それぞれ低
分子多価フェノール（平均重合度４）及び高分子多価フ
ェノール（平均重合度８）を示す。Seven-week-old, male ICR mice were group 6
Approximately 7 animals were fed a standard feed (CE-2) containing 0.75% iron powder (Wako Pure Chemical) for 4 weeks to prepare a lipid peroxidation model. To the sample-administered group, 0.75% of the sample was added to the iron-containing feed and administered, and the feed and water were freely taken. Blood was collected at the time of dissection and serum was separated from the blood. The antioxidant index was measured using a commercially available kit (SOD Test Wako, LPO Test Wako). The results are shown in FIG. In the figure, SO
D is a superoxide dismutase activity, LPO
Is a lipid peroxide, and the low molecular weight and the high molecular weight represent a low molecular weight polyhydric phenol (average degree of polymerization 4) and a high molecular weight polyhydric phenol (average degree of polymerization 8), respectively.
【００３７】図３から明らかなように、鉄配合飼料を投
与した脂質過酸化モデル・マウスでは、血中の脂質過酸
化物が増加していたが、高分子蕎麦多価フェノール分画
物の投与によってほぼ正常値まで低下した。また、鉄投
与が原因で低下していた血清中のＳＯＤ活性も、正常値
に回復した。As is apparent from FIG. 3, in the lipid peroxidation model mice to which the iron-containing diet was administered, the lipid peroxide in the blood was increased. Decreased to almost normal values. The SOD activity in the serum, which had been reduced due to the administration of iron, also returned to a normal value.
【００３８】[0038]
【発明の効果】本発明のカテキン・エピカテキンを構成
単位とする多価フェノール重合体は、脂質過酸化の抑
制、ＳＯＤ活性の上昇等の生理活性作用を示すので、こ
れを医薬品組成物、食品、飼料等に利用することが可能
である。特に脂質過酸化抑制、ＳＯＤ活性上昇等は生体
内の活性酸素種の生成抑制に関連し脳機能に悪影響を及
ぼす物質の除去に繋がることから、生体の脂質過酸化抑
制、ＳＯＤ活性上昇と共に、脳機能改善、脳の病的障害
の予防・改善等にも有用と考えられる。また、本発明の
多価フェノール重合体の原料は、長期間の食経験のある
蕎麦であり、急性、慢性いずれの毒性もなく、また蕎麦
種子抽出液を分画した製品であることから、蕎麦アレル
ギーの問題もないと考えられる。The polyhydric phenol polymer of the present invention comprising catechin / epicatechin as a constitutional unit exhibits a physiologically active action such as suppression of lipid peroxidation and increase of SOD activity. , Feed and the like. In particular, suppression of lipid peroxidation and increase in SOD activity are related to suppression of generation of reactive oxygen species in the living body and lead to removal of substances that have an adverse effect on brain function. It is also considered useful for improving functions, preventing and improving pathological disorders of the brain, and the like. In addition, the raw material of the polyhydric phenol polymer of the present invention is buckwheat having a long-term dietary experience, without acute or chronic toxicity, and because it is a product obtained by fractionating buckwheat seed extract, buckwheat It is thought that there is no allergy problem.
【図１】 蕎麦抽出成分のチオリシス反応終了時点での
ＨＰＬＣチャートである。FIG. 1 is an HPLC chart at the end of a thiolysis reaction of buckwheat extract components.
【図２】 本発明の多価フェノール重合体と抗酸化活性
の関係を示すグラフである。FIG. 2 is a graph showing the relationship between the polyphenolic polymer of the present invention and antioxidant activity.
【図３】 マウス過酸化モデルに本発明の多価フェノー
ル重合体を投与した際における血清中の過酸化脂質（Ｌ
ＰＯ）の変化（Ａ）とＳＯＤ活性の変化（Ｂ）を示す。FIG. 3 shows lipid peroxide (L) in serum when the polyhydric phenol polymer of the present invention was administered to a mouse peroxidation model.
PO) (A) and SOD activity (B).
フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 39/06 Ａ６１Ｐ 39/06 43/00 １１１ 43/00 １１１ (72)発明者 中川 喬 北海道札幌市清田区真栄363番32号 ハイ テクヒル真栄 株式会社アミノアップ化学 内 (72)発明者 向田 朋美 北海道札幌市清田区真栄363番32号 ハイ テクヒル真栄 株式会社アミノアップ化学 内 Ｆターム(参考） 2B150 DA09 DB01 DD31 4C062 FF44 4C086 AA01 AA02 AA03 BA08 MA01 MA04 NA14 ZA15 ZC19 ZC33Continuation of the front page (51) Int.Cl. 7 Identification symbol FI Theme coat II (reference) A61P 39/06 A61P 39/06 43/00 111 43/00 111 (72) Inventor Takashi Nakagawa 363 Maei, Kiyota-ku, Sapporo, Hokkaido, Japan No. 32 High Techhill Maei Co., Ltd. Amino Up Chemical Co., Ltd. (72) Inventor Tomomi Mukada 363-32 Mae, Kiyota-ku, Sapporo, Hokkaido High Techhill Maei Co., Ltd. Amino Up Chemical Co., Ltd. F term (reference) 2B150 DA09 DB01 DD31 4C062 FF44 4C086 AA01 AA02 AA03 BA08 MA01 MA04 NA14 ZA15 ZC19 ZC33
Claims (10)
置、β配置またはそれらの混合物を表わし、ｎは０また
は１以上の整数である。）で示される多価フェノール重
合体。1. A compound of the formula (I) (Wherein the configuration of the hydroxyl group at the 3-position of the chroman ring represents an α-configuration, a β-configuration or a mixture thereof, and n is 0 or an integer of 1 or more).
体における各クロマン環の３位の水酸基の立体配置を、
式（II） 【化２】 （式中、ｎは請求項１の記載に同じ。）のＸ1及びＸ2で
表わしたとき、Ｘ1のα配置／β配置比が約２であり、
Ｘ2のα配置／β配置比が約0.5である請求項１記載の多
価フェノール重合体。2. The configuration of the hydroxyl group at the 3-position of each chroman ring in the polyhydric phenol polymer represented by the formula (I)
Formula (II) (Where n is the same as in claim 1) and X 1 and X 2 , the α configuration / β configuration ratio of X 1 is about 2,
The polyhydric phenol polymer according to claim 1, wherein the α configuration / β configuration ratio of X 2 is about 0.5.
１または２記載の多価フェノール重合体。3. The polyhydric phenol polymer according to claim 1, wherein n is 0 or an integer of 1 to 7.
のいずれかに記載の多価フェノール重合体。4. A buckwheat extract obtained from buckwheat extract.
The polyhydric phenol polymer according to any one of the above.
いずれかに記載の多価フェノール重合体。5. The polyhydric phenol polymer according to claim 1, which has a physiological activity.
る請求項５に記載の多価フェノール重合体。6. The polyhydric phenol polymer according to claim 5, wherein the physiologically active action is a lipid peroxidation inhibitory action.
ターゼ活性上昇作用である請求項５に記載の多価フェノ
ール重合体。7. The polyhydric phenol polymer according to claim 5, wherein the physiologically active action is a superoxide dismutase activity increasing action.
を有効成分とする医薬組成物。8. A pharmaceutical composition comprising the polyhydric phenol polymer according to claim 5 as an active ingredient.
の医薬組成物。9. The pharmaceutical composition according to claim 8, which has a brain function improving effect.
パーオキシドジスムターゼ活性上昇作用を有する請求項
８に記載の医薬組成物。10. The pharmaceutical composition according to claim 8, which has a lipid peroxidation inhibitory action and / or a superoxide dismutase activity increasing action.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4903436B2 (en) * | 2004-02-17 | 2012-03-28 | サントリーホールディングス株式会社 | Lipase activity inhibitor, tea extract containing high-molecular polyphenol fraction, and method for producing the same |
| CN114712386A (en) * | 2021-03-31 | 2022-07-08 | 贝尔克斯生技股份有限公司 | High polymeric proanthocyanidin composition and its application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH10218786A (en) * | 1997-02-07 | 1998-08-18 | Amino Atsupu Kagaku:Kk | Medicine comprising buckwheat chaff extract as active ingredient |
| JP2000053575A (en) * | 1998-08-05 | 2000-02-22 | Amino Appu Kagaku:Kk | Composition for prevention and/or therapy of senescence |
| JP2000506901A (en) * | 1996-04-02 | 2000-06-06 | マーズ・インコーポレイテツド | Cocoa extract compounds and methods for making and using same |
-
2001
- 2001-02-21 JP JP2001044685A patent/JP4763139B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000506901A (en) * | 1996-04-02 | 2000-06-06 | マーズ・インコーポレイテツド | Cocoa extract compounds and methods for making and using same |
| JPH10218786A (en) * | 1997-02-07 | 1998-08-18 | Amino Atsupu Kagaku:Kk | Medicine comprising buckwheat chaff extract as active ingredient |
| JP2000053575A (en) * | 1998-08-05 | 2000-02-22 | Amino Appu Kagaku:Kk | Composition for prevention and/or therapy of senescence |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4903436B2 (en) * | 2004-02-17 | 2012-03-28 | サントリーホールディングス株式会社 | Lipase activity inhibitor, tea extract containing high-molecular polyphenol fraction, and method for producing the same |
| JP2012097085A (en) * | 2004-02-17 | 2012-05-24 | Suntory Holdings Ltd | Lipase activity inhibitor containing polymer polyphenol fraction and tea extract, and process for production the same |
| CN114712386A (en) * | 2021-03-31 | 2022-07-08 | 贝尔克斯生技股份有限公司 | High polymeric proanthocyanidin composition and its application |
| EP4066828A1 (en) * | 2021-03-31 | 2022-10-05 | Belx Bio-Pharmaceutical (Taiwan) Corporation | Polymeric proathocyanidin composition and application thereof |
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| JP4763139B2 (en) | 2011-08-31 |
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