JP2012017337A - Composition for alcohol metabolism promotion - Google Patents

Composition for alcohol metabolism promotion Download PDF

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JP2012017337A
JP2012017337A JP2011208931A JP2011208931A JP2012017337A JP 2012017337 A JP2012017337 A JP 2012017337A JP 2011208931 A JP2011208931 A JP 2011208931A JP 2011208931 A JP2011208931 A JP 2011208931A JP 2012017337 A JP2012017337 A JP 2012017337A
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hangover
food
alcohol
fermentation
drink
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Kenji Mizumoto
憲司 水本
Hajime Sasaki
一 佐々木
Makoto Yamaguchi
真 山口
Takaji Yajima
高二 矢島
Hideo Hasegawa
秀夫 長谷川
Yasushi Arima
裕史 有馬
Hideo Otomo
英生 大友
Kenichi Nakazawa
賢一 中澤
Eiji Negishi
栄志 根岸
Yasuko Sawai
保子 澤井
Masao Takami
政雄 高見
Daisuke Kozutsumi
大介 小堤
Masayo Arita
昌代 有田
Akitomo Kume
晃智 粂
Katsuyuki Uchida
勝幸 内田
Hajime Sumio
肇 角尾
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Meiji Co Ltd
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Meiji Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/62—Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12G—WINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
    • C12G3/00—Preparation of other alcoholic beverages
    • C12G3/04—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
    • C12G3/05—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides
    • C12G3/055—Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides extracted from plants

Abstract

PROBLEM TO BE SOLVED: To provide a unique composition for an alcohol metabolism promotion, which contains an alcohol fermentation product of citrus molasses or a mixed composition of the alcohol fermentation product and plant worm extract, promotes aldehyde dehydrogenase activity, and does not substantially affect alcohol dehydrogenase activity; and to also provide drinks and foods for preventing sick feel from drinking and hangover, which contain the composition for an alcohol metabolism promotion.SOLUTION: The vacuum concentrate of a fermentation product is obtained by subjecting citrus molasses to alcoholic fermentation using genus Saccharomyces yeast.

Description

本発明は、アルコール代謝促進剤組成物及び悪酔い又は二日酔い予防改善剤組成物に関する。   The present invention relates to an alcohol metabolism promoter composition and a hangover or hangover prevention improving composition.

経口的に摂取（飲酒）したアルコールの大部分は、上部消化管で吸収され、肝臓で代謝されるが、肝臓にはアルコールの酸化を規定する制御機構が存在していない。そのためアルコールを過剰に摂取すると、肝臓でのアルコール代謝が選択的に亢進し、その結果として肝臓内の代謝系に大きな変動を伴うことになる。摂取したアルコールの大部分は、肝細胞のサイトゾールに存在するアルコール脱水素酵素系を介してアセトアルデヒドとなり、アセトアルデヒドはさらにアルデヒド脱水素酵素による脱水素反応を受けて酢酸に変換される。アルコール摂取量が多すぎたり、体調が悪くてアルコールの代謝が遅れたりすると、アセトアルデヒドが処理しきれなくなり、血中のアセトアルデヒド濃度が高くなる。アセトアルデヒドは強い毒性があり、胃腸のムカツキ、吐き気、頭痛、二日酔い等の不快症状の原因となる。よって、アルコール摂取後に生じるアセトアルデヒドをいかに血中から速やかに消失させるかが悪酔いや二日酔いの予防に重要である。そこで、アルデヒド脱水素酵素の活性を高める作用を有する経口物質、すなわち、アセトアルデヒドの代謝を促進する経口物質は、上記の悪酔いや二日酔いの予防や改善に効果があると考えられる。このような経口物質として、例えば、とうもろこし蛋白質を酵素分解して得られる分子量200〜4,000のペプチドを有効成分とするアルコール代謝促進剤（特許文献１）、豚肉をプロテアーゼで処理して得られる豚肉加工品を含有するアルコール代謝促進作用物（特許文献２）、あるいはイソフラボノイドを有効成分とする二日酔い防止食品（特許文献３）、などが提供されている。   Most of the alcohol that is taken orally (drinked) is absorbed in the upper gastrointestinal tract and metabolized in the liver, but the liver does not have a control mechanism that regulates the oxidation of alcohol. Therefore, when alcohol is excessively consumed, alcohol metabolism in the liver is selectively enhanced, and as a result, the metabolic system in the liver is greatly changed. Most of the ingested alcohol is converted into acetaldehyde through the alcohol dehydrogenase system present in the cytosol of hepatocytes, and the acetaldehyde is further converted to acetic acid through a dehydrogenation reaction by the aldehyde dehydrogenase. If the amount of alcohol intake is too high, or if the physical condition is bad and the metabolism of alcohol is delayed, acetaldehyde cannot be completely processed, and the concentration of acetaldehyde in the blood increases. Acetaldehyde is highly toxic and causes discomfort such as gastrointestinal irritations, nausea, headache, and hangover. Therefore, how to quickly eliminate acetaldehyde generated after alcohol intake from the blood is important for prevention of hangover and hangover. Therefore, it is considered that an oral substance having an action of increasing the activity of aldehyde dehydrogenase, that is, an oral substance that promotes the metabolism of acetaldehyde is effective in preventing and improving the above-mentioned sickness and hangover. As such an oral substance, for example, an alcohol metabolism promoter (Patent Document 1) containing a peptide having a molecular weight of 200 to 4,000 obtained by enzymatic degradation of corn protein as an active ingredient, and pork processing obtained by treating pork with protease An alcohol metabolism promoting agent containing a product (Patent Document 2), a hangover food containing an isoflavonoid as an active ingredient (Patent Document 3), and the like are provided.

特開平7-285881号公報Japanese Unexamined Patent Publication No. 7-285881 特開平11-276116号公報JP-A-11-276116 特開平2000-7694号公報Japanese Unexamined Patent Publication No. 2000-7694

本発明は、アルデヒド脱水素酵素活性を促進するがアルコール脱水素酵素活性には実質的に影響しないユニークなアルコール代謝促進剤組成物を提供することを課題とする。また、該組成物を有効成分として含有する悪酔い又は二日酔い予防改善剤組成物を提供することを課題とする。   An object of the present invention is to provide a unique alcohol metabolism promoter composition that promotes aldehyde dehydrogenase activity but does not substantially affect alcohol dehydrogenase activity. It is another object of the present invention to provide an agent for preventing or improving hangover or hangover containing the composition as an active ingredient.

本発明者らは、ラットに対し、柑橘糖蜜のアルコール発酵産物の濃縮液に冬虫夏草抽出物を配合した組成物を、エタノール経口投与前に予め経口投与しておくと、対照に対して、血中エタノール濃度には有意な変化は認められなかったが、血中アセトアルデヒド濃度は有意に低下することを見出した。この結果がどのような作用機序に起因しているかを、柑橘糖蜜のアルコール発酵産物の濃縮液を添加した酵素反応系で調べたところ、該濃縮物は、アルデヒド脱水素酵素の活性を増強する作用があり、一方、アルコール脱水素酵素の活性には影響を及ぼさないことから、この濃縮物が悪酔い又は二日酔いの予防改善に有用であることを見出した。   The present inventors have previously orally administered to a rat a composition obtained by blending Cordyceps extract with a concentrated citrus molasses alcohol fermented alcohol product prior to oral administration of ethanol. Although no significant change was observed in the ethanol concentration, it was found that the blood acetaldehyde concentration was significantly reduced. When the enzyme reaction system to which the concentrated liquid of the alcoholic fermentation product of citrus molasses was added was examined to determine the action mechanism of this result, the concentrate enhanced the activity of aldehyde dehydrogenase. It has an effect, but does not affect the activity of alcohol dehydrogenase. Therefore, it has been found that this concentrate is useful for the prevention and improvement of hangover or hangover.

すなわち、本発明は、柑橘糖蜜をサッカロミセス属酵母を用いてアルコール発酵させて得られる発酵産物を含有するアルコール代謝促進剤組成物及び悪酔い又は二日酔い予防改善用組成物を提供するものである。
また、本発明は上記発酵産物及び冬虫夏草抽出物を含有するアルコール代謝促進剤組成物及び悪酔い又は二日酔い予防改善剤組成物を提供するものである。
さらに本発明は上記発酵産物の、アルコール代謝促進剤組成物及び悪酔い又は二日酔い予防改善用組成物製造のための使用を提供するものである。
さらに、本発明は上記発酵産物及び冬虫夏草抽出物の、アルコール代謝促進剤組成物及び悪酔い又は二日酔い予防改善用組成物製造のための使用を提供するものである。
さらに、本発明は上記組成物の有効量を投与することを特徴とするアルコール代謝促進方法、及び悪酔い又は二日酔い予防改善方法を提供するものである。
さらにまた本発明は上記組成物及び冬虫夏草抽出物の有効量を投与することを特徴とするアルコール代謝促進方法、及び悪酔い又は二日酔い予防改善方法を提供するものである。 That is, the present invention provides an alcohol metabolism promoter composition containing a fermented product obtained by subjecting citrus molasses to alcohol fermentation using Saccharomyces yeasts, and a composition for preventing or improving hangover or hangover.
The present invention also provides an alcohol metabolism promoter composition and a hangover or hangover prevention / improving agent composition containing the fermentation product and Cordyceps extract.
Furthermore, the present invention provides use of the above fermentation product for producing an alcohol metabolism promoter composition and a composition for improving the prevention of hangover or hangover.
Furthermore, the present invention provides the use of the above fermentation product and Cordyceps extract for the production of an alcohol metabolism promoter composition and a composition for improving the prevention of hangover or hangover.
Furthermore, the present invention provides a method for promoting alcohol metabolism, and a method for preventing and improving hangover or hangover characterized by administering an effective amount of the above composition.
Furthermore, the present invention provides a method for promoting alcohol metabolism and a method for preventing and improving hangover or hangover characterized by administering an effective amount of the above composition and Cordyceps extract.

ラットに対する、柑橘糖蜜の発酵産物の濃縮物２,０００mg/kg経口投与、及び冬虫夏草抽出物２００mg/kg＋濃縮物２０００mg/kg経口投与が、その後のエタノール経口投与による血中アルコール濃度におよぼす影響を示すグラフである。The effect of oral administration of 2,000 mg / kg concentrate of citrus molasses fermented product and oral administration of Cordyceps extract 200 mg / kg + 2000 mg / kg concentrate on rat blood alcohol concentration by subsequent oral administration of ethanol is shown. It is a graph. 血中アセトアルデヒド濃度におよぼす影響を示すグラフである。＊：ｐ＜０.０５（Student's test）It is a graph which shows the influence which acts on the blood acetaldehyde density | concentration. *: P <0.05 (Student's test) in vitroにおける柑橘糖蜜の発酵産物の濃縮物のアルコール脱水素酵素活性に及ぼす効果を示す図である。It is a figure which shows the effect on the alcohol dehydrogenase activity of the concentrate of the fermentation product of citrus molasses in vitro. アルデヒド脱水素酵素活性に及ぼす効果を示す図である。It is a figure which shows the effect which acts on aldehyde dehydrogenase activity.

柑橘糖蜜の製造法は公知である（例えば特開平10-276578）。温州みかんなどの柑橘類を搾汁して果汁を製造するときに発生する搾汁粕は、約１０〜１５％の可溶性固形物を含んでおり含水量が多い。この搾汁粕（外果皮、果皮、及びじょうのう膜を含む）に、脱水を容易にするために消石灰を加えライミングを行った後圧搾して得た搾汁を、Ｂｒｉｘ５０〜７０％に濃縮した粘ちょう状の液は、「柑橘糖蜜」とよばれる。また、柑橘糖蜜からパルプなどの不溶性成分を除去したものは、「脱パルプ柑橘糖蜜」とよばれ、これも本発明に使用できる。   The manufacturing method of citrus molasses is well-known (for example, Unexamined-Japanese-Patent No. 10-276578). Juice lees generated when juice is produced by squeezing citrus fruits such as Wenzhou mandarin orange contains about 10-15% soluble solids and has a high water content. The juice obtained by squeezing after adding slaked lime to facilitate dehydration to this squeezed rice cake (including the outer skin, pericarp, and gills) is concentrated to Brix 50 to 70%. The viscous liquid is called “citrus molasses”. Moreover, what removed insoluble components, such as a pulp, from citrus molasses is called "depulped citrus molasses", and this can also be used for this invention.

柑橘類としては、温州みかん以外に、例えば、夏みかん、伊予柑、グレープフルーツ、マンダリンオレンジ、レモンなどの柑橘、あるいはユズ、カボス、スダチ、ダイダイ、サンポウカンなどが含まれる。   Examples of citrus include citrus such as summer orange, Iyokan, grapefruit, mandarin orange, and lemon, or yuzu, kabosu, sudachi, daidai, sampoukan and the like in addition to Wenzhou oranges.

本発明により、アルコール摂取前に温州みかん等の柑橘糖蜜の発酵産物を経口摂取すると、血中アセトアルデヒドが低下することが明らかとなった。そして、この現象は、該発酵産物がアセトアルデヒド代謝酵素活性を高める作用に基づくものであることが明らかとなった。すなわち、柑橘糖蜜の発酵産物からなる組成物は、悪酔いや二日酔いに有効であることが明らかにされた。   According to the present invention, it has been clarified that when a fermented product of citrus molasses such as Unshu mandarin orange is orally ingested before alcohol intake, blood acetaldehyde is lowered. And this phenomenon became clear that this fermentation product was based on the effect | action which raises acetaldehyde metabolic enzyme activity. That is, it has been clarified that a composition comprising a fermentation product of citrus molasses is effective for hangover and hangover.

柑橘糖蜜を酵母を用いてアルコール発酵することにより、本発明のアルコール代謝促進作用を有する組成物が得られる。柑橘糖蜜のアルコール発酵は、当業者公知の、廃糖蜜を原料とするアルコール発酵法に準じて行うことができる。   By subjecting citrus molasses to alcohol fermentation using yeast, the composition having the effect of promoting alcohol metabolism of the present invention can be obtained. Alcohol fermentation of citrus molasses can be performed according to an alcohol fermentation method using waste molasses as a raw material, which is known to those skilled in the art.

柑橘糖蜜は不溶性のパルプ含量が高いため、食品素材として使用するには、遠心分離できるように希釈して遠心分離し、パルプを除去することが好ましい。この脱パルプ柑橘糖蜜は、酵母が資化可能な糖質を多量に含んでいる。そこで、有効成分の濃縮を目的に、脱パルプ柑橘糖蜜を酵母でアルコール発酵処理し、該柑橘糖蜜中の資化糖を、エタノール及び炭酸ガスに変換して有効成分の比率を高める処理をする。   Since citrus molasses has a high content of insoluble pulp, it is preferable to remove the pulp by diluting and centrifuging so that it can be centrifuged for use as a food material. This depulped citrus molasses contains a large amount of sugar that can be assimilated by yeast. Therefore, for the purpose of concentrating the active ingredient, the depulped citrus molasses is subjected to alcoholic fermentation with yeast, and the assimilated sugar in the citrus molasses is converted into ethanol and carbon dioxide to increase the ratio of the active ingredients.

脱パルプ柑橘糖蜜を水で希釈して、糖度を１０〜２０％程度に調整する。栄養源として硫酸アンモニウム、アンモニア水、尿素などの窒素源、さらに必要あれば、過燐酸石灰、リン酸アンモニウムなどのリン酸塩を加える。pHをほぼ５に調整して加熱殺菌（６０℃で３０分、あるいは８５℃で１５分）する。冷却（３０〜３５℃）した後、酵母を加えアルコール発酵させる。発酵温度は、２７±７℃である。酵母としては、市販のパン酵母Saccharomyces cerevisiaeが最もよいが、その他の酵母、例えば、S. formosensis、S. carlsbergensis、S. ellipsoideus、S. rouxii、あるいはS. sakeなども用いてみてもよい。 The depulped citrus molasses is diluted with water to adjust the sugar content to about 10 to 20%. Nitrogen sources such as ammonium sulfate, aqueous ammonia and urea are added as nutrient sources, and phosphates such as lime perphosphate and ammonium phosphate are added if necessary. Adjust the pH to approximately 5 and heat sterilize (30 minutes at 60 ° C. or 15 minutes at 85 ° C.). After cooling (30 to 35 ° C.), yeast is added to cause alcohol fermentation. The fermentation temperature is 27 ± 7 ° C. As the yeast, the commercially available baker's yeast Saccharomyces cerevisiae is the best, but other yeasts such as S. formosensis , S. carlsbergensis , S. ellipsoideus , S. rouxii , or S. sake may also be used.

発酵が進むにつれて、Ｂｒｉｘ糖度は低下する。発酵終了は、３０分経過時のＢｒｉｘ糖度変化が０.１％以下を目安とする。発酵産物は、粘ちょう度が低下しており、さらに有効成分を濃縮することが可能である。濃縮液は、菌体分離、清澄化、殺菌、濃縮、再殺菌の工程を経て、最終的に本発明のアルコール代謝促進組成物が得られる。この組成物は、さらに乾燥粉末としてもよい。   As fermentation proceeds, the Brix sugar content decreases. For the end of fermentation, the Brix sugar content change after 30 minutes is set to 0.1% or less. The fermented product has a reduced consistency and can further concentrate active ingredients. The concentrated liquid is finally subjected to the steps of cell separation, clarification, sterilization, concentration, and re-sterilization to obtain the alcohol metabolism promoting composition of the present invention. This composition may further be a dry powder.

冬虫夏草は、子嚢菌類（Ascomycetes）、麦角菌目（Clavicipitales）、麦角菌科（Hypocreaceae）、冬虫夏草属（Cordyceps）に属し、完全世代と不完全世代とを有する微生物である。冬虫夏草は、その子実体が、不老長寿の妙薬として、あるいは滋養強壮の妙薬として、古来より珍重されてきた。このようにして従来より漢方薬として珍重されてきた冬虫夏草は、通常、子実体を粉末化し、これを服用するものである。 Cordyceps belongs to Ascomycetes , Clavicipitales , Hypocreaceae , Cordyceps , and has a complete generation and an incomplete generation. Cordyceps has been prized since ancient times for its fruiting body as a potion for immortality and longevity or as a nourishing potion. As described above, cordyceps, which has been prized as a traditional Chinese medicine, is usually obtained by powdering fruit bodies and taking them.

本発明で用いる冬虫夏草は、上記子実体も用いることができると考えられるが、Cordyceps sinensis(Berk.) SaccやCordyceps militarisの菌糸体は大量培養が可能であり、これらの培養菌糸体から熱水で有効成分を抽出して得られる抽出物（例えばWO96/00580及び特開平8-12588号）を用いるのがよい。該抽出物を柑橘糖蜜の発酵産物に添加すると、アルデヒド脱水素酵素活性をさらに高めることが明らかにされた。冬虫夏草菌糸体の培養及び抽出操作は、公知方法（例えばWO96/00580及び特開平8-12588号）である。 Cordyceps sinensis (Berk.) Sacc and Cordyceps militaris mycelium can be cultivated in large quantities, and cordyceps sinensis (Berk.) Sacc and mycelium can be cultured in hot water. An extract obtained by extracting an active ingredient (for example, WO96 / 00580 and JP-A-8-12588) may be used. It has been shown that addition of the extract to the fermentation product of citrus molasses further increases aldehyde dehydrogenase activity. The cultivation and extraction of Cordyceps mycelium is a known method (for example, WO96 / 00580 and JP-A-8-12588).

すなわち、Cordyceps sinensisの培養菌子体を、麦芽エキス、酵母エキス、ペプトン、バレイショ煮出汁、ブドウ糖、ビタミン類、アミノ酸、核酸、蛋白質、及び必要に応じ、昆虫等寄主の成分などを加えた培地に接種し、液体又は固体培養を行う。大量培養の場合は、通気攪拌型発酵槽（１００〜３００rpm）による液体培養を用いる。培養は、pH４〜７、培養温度２０〜３０℃、３〜１０日間行う。培養終了後、培養菌子体を熱水（８５〜１００℃）抽出する。あるいは水又は水に可溶性の少量の酸、塩基又は有機溶媒を含む水系溶媒にて抽出してもよい。遠心分離、あるいは濾過などにより残さを取り除く。得られた冬虫夏草の熱水抽出物は、そのまま本発明に使用してもよいが、常法により濃縮、あるいは凍結乾燥粉末として使用してもよい。 That is, inoculate the cultured mycelium of Cordyceps sinensis into a medium containing malt extract, yeast extract, peptone, potato boiled juice, glucose, vitamins, amino acids, nucleic acids, proteins, and if necessary, host ingredients such as insects And liquid or solid culture. In the case of mass culture, liquid culture using an aeration and stirring type fermenter (100 to 300 rpm) is used. Culture is performed at pH 4-7, culture temperature 20-30 ° C., for 3-10 days. After completion of the culture, the cultured mycelia are extracted with hot water (85 to 100 ° C.). Alternatively, it may be extracted with water or an aqueous solvent containing a small amount of acid, base or organic solvent soluble in water. Remove the residue by centrifugation or filtration. The obtained hot water extract of Cordyceps sinensis can be used in the present invention as it is, but it may be concentrated by a conventional method or used as a freeze-dried powder.

柑橘糖蜜の発酵産物を、アルコール摂取前に摂取すると、血中アセトアルデヒドが低下する。また、発酵産物と冬虫夏草の抽出物を併せて摂取すると血中アセトアルデヒドがさらに低下する。すなわち、柑橘糖蜜の発酵産物、あるいは該発酵産物と冬虫夏草の抽出物との混合組成物を摂取すると、悪酔いや二日酔い予防改善効果が得られる。この予防効果は、上記したように、柑橘糖蜜の発酵産物がアルデヒド脱水素酵素の活性を高める作用に基づく。冬虫夏草の抽出物にはアルデヒド脱水素酵素の活性を高める作用は認められない。冬虫夏草抽出物が該酵素活性を高める理由は明らかではないが、冬虫夏草抽出物には、肝血流量の増加作用（Food Style 21, vol.2, No.5, 1998）、及び肝臓でのＡＴＰ産生量を高める作用（Jpn. J. PHarmacol., 70: 85-88, 1996）が知られている。冬虫夏草抽出物による肝血流量の増加は、該発酵産物の肝臓への流入を促進し、肝細胞内のアルデヒド脱水素酵素活性を高めると考えられる。また、アルデヒド脱水素酵素が作用するには、補酵素のＮＡＤが必要であり、ＮＡＤはニコチン酸とＡＴＰより合成されることから、ＡＴＰ量の増大は、結果的にＮＡＤの合成を促進し、アルデヒド脱水素酵素の活性を高めると考えられる。   If the fermented citrus molasses is ingested before ingesting alcohol, blood acetaldehyde will decrease. In addition, intake of fermented products and Cordyceps extract will further reduce blood acetaldehyde. That is, when a citrus molasses fermented product or a mixed composition of the fermented product and Cordyceps sinensis extract is ingested, the effects of preventing and improving hangover and hangover are obtained. As described above, this preventive effect is based on the effect that the fermentation product of citrus molasses enhances the activity of aldehyde dehydrogenase. The extract of Cordyceps sinensis does not increase the activity of aldehyde dehydrogenase. It is not clear why Cordyceps extract increases the enzyme activity, but Cordyceps extract increases liver blood flow (Food Style 21, vol.2, No.5, 1998) and produces ATP in the liver. The effect of increasing the amount (Jpn. J. PHarmacol., 70: 85-88, 1996) is known. It is considered that the increase in hepatic blood flow by Cordyceps extract promotes the inflow of the fermentation product into the liver and enhances aldehyde dehydrogenase activity in hepatocytes. In addition, in order for aldehyde dehydrogenase to act, the coenzyme NAD is required, and since NAD is synthesized from nicotinic acid and ATP, an increase in the amount of ATP eventually promotes the synthesis of NAD, It is thought to increase the activity of aldehyde dehydrogenase.

柑橘糖蜜の発酵産物中のアルデヒド脱水素酵素活性を高める成分を分析した結果、いくつかの成分が含まれていることが判明したが、これら成分の有効濃度と発酵産物中の含有量を考慮すると、発酵産物の該作用を、これら各成分の有するそれぞれの作用で説明することはできない。また、これらの成分を発酵産物の含有量割合に混合した組成物も、発酵産物の該作用を説明できない。その結果、発酵産物のアルデヒド脱水素酵素の活性を高める作用は、発酵産物含有成分の複合的な作用に基づくものであると考えられる。   As a result of analyzing components that enhance aldehyde dehydrogenase activity in the fermentation product of citrus molasses, it was found that some components were included, but considering the effective concentration of these components and the content in the fermentation product The action of the fermentation product cannot be explained by the action of each of these components. In addition, a composition in which these components are mixed in the content ratio of the fermentation product cannot explain the action of the fermentation product. As a result, it is considered that the action of increasing the activity of the aldehyde dehydrogenase of the fermentation product is based on the combined action of the fermentation product-containing components.

柑橘糖蜜の発酵産物、あるいは該発酵産物と冬虫夏草抽出物との混合組成物の摂取時期は、アルコール摂取前が望ましいと考えられるが、その作用機作から、アルコール摂取時、あるいは摂取後でも、悪酔いや二日酔いの軽減に効果が期待できる。該組成物を予め摂取しておくことにより、アルデヒド脱水素酵素の活性が高まり、飲酒により生じる有害な血中アセトアルデヒドが低下するが、一方、アルコール脱水素酵素の活性に対しては実質的な影響はなく、飲酒の楽しさである“ほろ酔い気分”をこわさずに、悪酔いや二日酔いを予防する、というユニークな作用が得られる。   It is considered that the intake time of the fermented citrus molasses product or the mixed composition of the fermented product and Cordyceps sinensis extract is desirable before ingesting alcohol. And can be expected to reduce hangovers. By ingesting the composition in advance, the activity of aldehyde dehydrogenase is increased, and harmful blood acetaldehyde caused by drinking is reduced. On the other hand, there is a substantial effect on the activity of alcohol dehydrogenase. The unique effect is to prevent hangover and hangover without disturbing the “feeling of tipsy” that is the pleasure of drinking.

柑橘糖蜜の発酵産物は、風味が良好でそのまま経口摂取可能であるので、悪酔いや二日酔い予防のために、該発酵産物を、その有効量を含む剤型に製剤化して用いることもできる。このような製剤技術は当業者に周知である。有効量は、アルコールを同量飲んでも、その吸収代謝速度は、体重、体質などの違いにより非常に個人差が大きく、明確には算定することはできないが、ラットの試験結果から、約１〜１０ｇ（乾燥固形分換算）／成人と推定される。毒性に関しては、柑橘糖蜜は食品素材として長年用いられてきており、長年の食経験からその安全性は保証されている。   Since the fermented citrus molasses has a good flavor and can be taken orally as it is, the fermented product can be formulated into a dosage form containing an effective amount thereof for prevention of hangover and hangover. Such formulation techniques are well known to those skilled in the art. The effective amount of absorption even if the same amount of alcohol is consumed, the absorption metabolic rate is very large due to individual differences due to differences in body weight, constitution, etc., and cannot be calculated clearly. Estimated to be 10 g (in terms of dry solids) / adult. In terms of toxicity, citrus molasses has been used as a food material for many years, and its safety is guaranteed from years of eating experience.

また、本発明の発酵産物、あるいは該発酵産物と冬虫夏草抽出物を、悪酔いや二日酔い予防のために、飲食時にその有効量を直接飲食品に添加して用いてもよい。また、有効量を含む飲食品に加工してもよい。例えば、ドリンク剤として、糖質１０％、酸味量０.１％、果汁２〜３％、フレーバー０.１％、に柑橘糖蜜の発酵産物５.３％、及び冬虫夏草抽出エキス１.７％を加えて、pHを３.５〜４.０に調整した後、６５℃で１０分間加熱殺菌し、次いで冷却・瓶詰めする。さらに、該ドリンク剤に脂肪酸の代謝改善効果を有するγ-リノレン酸及び／又はアラキドン酸カスケード内の脂肪酸を添加して、肝臓の脂質代謝機能の増進を補完することが考えられる。同様に他の機能性ドリンク剤、特定保健用食品などに配合してもよい。   In addition, the fermented product of the present invention, or the fermented product and Cordyceps extract may be used by adding an effective amount thereof directly to the food or drink during eating or drinking in order to prevent hangover or hangover. Moreover, you may process into the food / beverage products containing an effective amount. For example, as a drink, sugar 10%, acidity 0.1%, fruit juice 2-3%, flavor 0.1%, citrus molasses fermented product 5.3%, Cordyceps extract 1.7% In addition, after adjusting the pH to 3.5-4.0, it is sterilized by heating at 65 ° C. for 10 minutes, and then cooled and bottled. Furthermore, it is conceivable to add to the drink a fatty acid in the cascade of γ-linolenic acid and / or arachidonic acid, which has an effect of improving fatty acid metabolism, to complement the enhancement of liver lipid metabolism function. Similarly, you may mix | blend with another functional drink agent, the food for specific health, etc.

飲食品としては、上記の他、健康食品、栄養補助食品、及び治療用食品を含んでもよい。さらに、飲酒後の口臭を軽減するために、口臭予防作用を有する食品（例えば緑茶ポリフェノール）を併用してもよい。   In addition to the above, the food and drink may include health foods, nutritional supplements, and therapeutic foods. Furthermore, in order to reduce bad breath after drinking, a food having a bad breath prevention action (for example, green tea polyphenol) may be used in combination.

柑橘糖蜜の発酵産物に冬虫夏草抽出物を添加（配合）する場合は、その配合割合（重量）は、発酵産物：冬虫夏草エキス＝２０〜３０：１〜３程度（固形分換算）と推定されるが、最適配合割合は、当業者であれば、さらなる実験により容易に決定することができるので、このようにして決定された配合割合も本発明に包含される。得られた混合組成物は均一であることが好ましい。   When the Cordyceps extract is added (mixed) to the fermented citrus molasses, the blending ratio (weight) is estimated to be about fermentation product: Cordyceps extract = 20-30: 1-3 (solid content conversion). Since the optimum blending ratio can be easily determined by a person skilled in the art through further experiments, the blending ratio thus determined is also included in the present invention. The obtained mixed composition is preferably uniform.

本発明の発酵産物と冬虫夏草抽出物との混合組成物に加うるに、さらにアミノ酸を含有させてもよい。アミノ酸を含有させることにより、アルコールの胃や腸での吸収の阻害作用を補完させたり、ＮＡＤ系に関与してアルコール代謝を促進させることができる（Biol. PHarm. Bull., 18(12): 1653-1656, 1995; Alcoholand Aldehyde metabolizing system-IV: p.109, 1980）。アミノ酸としては、例えば、グリシン、Ｌ-アスパラギン酸、Ｌ-システィン、Ｌ-セリン、Ｌ-アラニン、Ｌ-メチオニンなどが挙げられる。   In addition to the mixed composition of the fermented product of the present invention and Cordyceps extract, an amino acid may be further contained. By containing amino acids, it is possible to supplement the inhibitory action of alcohol absorption in the stomach and intestines and to promote alcohol metabolism by participating in the NAD system (Biol. PHarm. Bull., 18 (12): 1653-1656, 1995; Alcoholand Aldehyde metabolizing system-IV: p.109, 1980). Examples of amino acids include glycine, L-aspartic acid, L-cysteine, L-serine, L-alanine, L-methionine and the like.

以下、実施例及び試験例により本発明を具体的に説明するが、本発明はこれらの実施例に限定されるものではない。   EXAMPLES Hereinafter, although an Example and a test example demonstrate this invention concretely, this invention is not limited to these Examples.

［実施例１］ 柑橘糖蜜の発酵産物の濃縮
温州みかん１０００kgをインライン搾汁機で搾汁して、果汁５００kgと搾汁粕５００kgを得た。この搾汁残さ５００kgに消石灰を加え（約０．３％）、ライミングした後圧搾して搾汁液２５０kgと搾汁粕２５０kgを得た。この搾汁液をＢｒｉｘ糖度４０〜５０％まで循環濃縮して柑橘糖蜜５０kg（Ｂｒｉｘ４５％、pH８〜９）を得た。柑橘糖蜜は、使用時まで冷凍保管した。
この柑橘糖蜜を解凍し、クエン酸でpH調整（pH６．０±０．５、１０±５℃）後、熱水で希釈（５０℃以上、Ｂｒｉｘ１０±５％）し、遠心分離（5100G）して不溶性成分（パルプ質）を除去した。パルプ質を除去した糖蜜はプレート殺菌（８８℃・１５秒保持）した後、プレート式濃縮機で濃縮し、１０℃以下に冷却した。Ｂｒｉｘ調整（Ｂｒｉｘ５０±１％、パルプ２０％以下、pH６.０±１）を脱パルプ糖蜜３７kg得た。 [Example 1] Concentration of fermentation product of citrus molasses 1000 kg of Wenzhou mandarin orange was squeezed with an in-line squeezer to obtain 500 kg of fruit juice and 500 kg of squeeze cake. Slaked lime was added to about 500 kg of the squeezed residue (about 0.3%), and after rimming, squeezed to obtain 250 kg of juice and 250 kg of juice. This juice was circulated and concentrated to a Brix sugar content of 40 to 50% to obtain 50 kg of citrus molasses (Brix 45%, pH 8 to 9). Citrus molasses was stored frozen until use.
Thaw the citrus molasses, adjust pH with citric acid (pH 6.0 ± 0.5, 10 ± 5 ° C), dilute with hot water (over 50 ° C, Brix10 ± 5%), and centrifuge (5100G). Insoluble components (pulpaceous matter) were removed. The molasses from which the pulp was removed was sterilized on a plate (88 ° C., maintained for 15 seconds), concentrated with a plate type concentrator, and cooled to 10 ° C. or lower. 37 kg of depulped molasses was obtained with Brix adjustment (Brix 50 ± 1%, pulp 20% or less, pH 6.0 ± 1).

脱パルプ糖蜜を温水に溶解した。栄養源（窒素源）として硫酸アンモニウム、消泡剤としてアワブレークＧ-１０９、pH調整剤としてクエン酸を、それぞれ５倍量の水に溶解して上記脱パルプ糖蜜仕込み液に添加した。仕込み液はＢｒｉｘ糖度１３±１％、pH５±０.２となるように調整した。仕込み液中の脱パルプ糖蜜量は２７％（重量）であった。仕込み液は、バッチ殺菌（８５℃、１５分）後、３４±４℃まで冷却した。仕込み液にパン酵母（０.５％）を接種して発酵させた。酵母は、脱パルプ柑橘糖蜜中に含まれる糖を資化して炭酸ガスを発生し、発酵が進むにつれて、Ｂｒｉｘ糖度とpHは低下する。発酵時間はおよそ５〜６時間である。発酵終了時点は、３０分経過時のＢｒｉｘ糖度変化が０.１％以下の時を目安とする。発酵終了後、加熱（８５℃、１５分）して酵母を失活させた後、発酵液に含まれるスラッジ（酵母菌体、パルプ）を全自動圧搾機及びフィルタープレスで除去した。次いで、その上清をプレート殺菌（１３４℃、３秒）した。殺菌時に生じる不溶性成分をキュノーフィルターで除去後、減圧濃縮した。この濃縮物は再殺菌（８℃、３０秒）後冷却して、本発明のアルコール代謝促進組成物（Ｂｒｉｘ４５±２％）１０kgを得た。   The depulped molasses was dissolved in warm water. Ammonium sulfate as a nutrient source (nitrogen source), Awabreak G-109 as an antifoaming agent, and citric acid as a pH adjuster were each dissolved in 5 times the amount of water and added to the above depulped molasses charging solution. The feed solution was adjusted to a Brix sugar content of 13 ± 1% and a pH of 5 ± 0.2. The amount of depulped molasses in the feed liquid was 27% (weight). The charged solution was cooled to 34 ± 4 ° C. after batch sterilization (85 ° C., 15 minutes). The feed solution was inoculated with baker's yeast (0.5%) and fermented. Yeast assimilate the sugar contained in the depulped citrus molasses to generate carbon dioxide, and as the fermentation proceeds, the Brix sugar content and pH decrease. The fermentation time is approximately 5-6 hours. The end of fermentation is taken as a guide when the Brix sugar content change after 30 minutes is 0.1% or less. After completion of the fermentation, the yeast was deactivated by heating (85 ° C., 15 minutes), and then sludge (yeast cells, pulp) contained in the fermentation broth was removed with a fully automatic press and a filter press. The supernatant was then sterilized (134 ° C., 3 seconds). Insoluble components produced during sterilization were removed with a Cuno filter and concentrated under reduced pressure. This concentrate was re-sterilized (8 ° C., 30 seconds) and then cooled to obtain 10 kg of the composition for promoting alcohol metabolism (Brix 45 ± 2%) of the present invention.

［実施例２］ 冬虫夏草抽出物の製造
Ｍ２０Ｙ２培地１５０mLを５００mL容三角フラスコに採りオートクレーブ滅菌した。この培地に、Cordyceps sinensis MF-20008（FERM BP-5149）の凍結保存菌糸体１mLを接種し、２５℃、１８０rpmで５日間振とう培養した。これを種菌として、以下のように１５０Ｌ大量培養を行った。
Ｄ培地（１Ｌ中の組成：蔗糖 ４０.０ｇ、K2HPO4 ４.０ｇ、アスパラギン０.５ｇ、(NH4)2HPO4 ２.０ｇ、MgSO4・7H2O ２.０ｇ、CaCO3 ０.２５ｇ、CaCl2０.１ｇ、酵母エキスB-2 ４.０ｇ、pH５.６）１５０Ｌを、１５０ Ｌファーメンターに無菌濾過処理後投入し、上記の種培養液１５０mLを接種し、２５℃、pH ５.５、DO ５０％に制御し、１５７rpmで攪拌しながら、３日間培養した。この間、発生する泡は、シリコン消泡剤投入により処理した。培養により得られた１５０Ｌ培養液を、クラリファイヤーにより菌体分離処理を行い、菌体の水懸濁液を得た。これを９０から９５℃の間で、２時間保持することにより加熱抽出処理を行った後、クラリファイヤーによる清澄化を行い、上清液を得た。これを０.４５μｍ、及び０.２２μｍ無菌フィルターを用い濾過し、淡黄色の熱水抽出液８０Ｌ（固形物乾燥重量８００ｇ）を得た。 [Example 2] Manufacture of Cordyceps extract 150 mL of M20Y2 medium was placed in a 500 mL Erlenmeyer flask and sterilized by autoclave. This medium was inoculated with 1 mL of cryopreserved mycelium of Cordyceps sinensis MF-20008 (FERM BP-5149) and cultured with shaking at 25 ° C. and 180 rpm for 5 days. Using this as an inoculum, large-scale culture of 150 L was performed as follows.
D medium (composition in 1 L: sucrose 40.0 g, K 2 HPO 4 4.0 g, asparagine 0.5 g, (NH 4 ) 2 HPO 4 2.0 g, MgSO 4 .7H 2 O 2.0 g, CaCO 3 0 150 g of .25 g, CaCl 2 0.1 g, yeast extract B-2 4.0 g, pH 5.6) was put into a 150 L fermenter after aseptic filtration, inoculated with 150 mL of the above seed culture, The pH was controlled at 5.5 and DO 50%, and the cells were cultured for 3 days with stirring at 157 rpm. During this time, the generated foam was treated by adding a silicon antifoaming agent. The 150 L culture solution obtained by the culture was subjected to cell separation treatment with a clarifier to obtain an aqueous suspension of the cells. This was heated and extracted by holding it at 90 to 95 ° C. for 2 hours, and then clarified with a clarifier to obtain a supernatant. This was filtered using 0.45 μm and 0.22 μm aseptic filters to obtain 80 L of a pale yellow hot water extract (solid dry weight 800 g).

［実施例３］ 二日酔い予防ドリンク剤の製造
以下の原料配合割合（単位：kg）で二日酔い予防ドリンク剤を製造した。
柑橘糖蜜発酵産物の濃縮液（製造例１で得られたもの）： ５２．５
冬虫夏草抽出物（製造例２で得られたもの） ： １６．７
糖 ： ４０
果汁 ：１００
アスコルビン酸 ： １
クエン酸 ： ３
香料 ： ４
水 ：７８２．８
全量 １０００ [Example 3] Production of hangover prevention drink A hangover prevention drink was produced at the following raw material blending ratio (unit: kg).
Concentrated liquid of citrus molasses fermentation product (obtained in Production Example 1): 52.5
Cordyceps extract (obtained in Production Example 2): 16.7
Sugar: 40
Fruit juice: 100
Ascorbic acid: 1
Citric acid: 3
Fragrance: 4
Water: 782.8
Total amount 1000

上記を溶解し９５℃で２０分間殺菌した後、ビンに無菌的に１２０mLづつ充填し二日酔い予防ドリンク剤を得た。   After dissolving the above and sterilizing at 95 ° C. for 20 minutes, the bottle was aseptically filled with 120 mL each to obtain a hangover prevention drink.

［試験例１］ アルコール代謝促進作用（in vivo）
６週齢の雄性ウイスター系ラット（体重１６０〜１７０g）を用いた。試験物質として実施例１で得た柑橘糖蜜の発酵産物の濃縮物と実施例２で得た冬虫夏草抽出物を用いた。試験群として、（１）濃縮物２,０００mg/kg投与群、（２）冬虫夏草抽出物２００mg/kg＋濃縮物２,０００mg/kg投与群、及び（３）陰性対照群として蒸留水投与群（１０mL/kg）の３群 （１群６匹）を設定した。２４時間絶食後、蒸留水に溶解した濃縮物溶液、あるいは蒸留水を１０mL/kg体重となるように経口投与した。その１時間後に、２０％（Ｗ/Ｖ）エタノールを１０mL/kg体重となるように経口投与した。エタノール投与１時間後にエーテル麻酔下で大腿静脈より採血した。さらにエタノール投与３時間後にエーテル麻酔下で後大静脈より採血した。血中エタノール濃度は、F-キットエタノール（ロシュ・ダイアグノスティックス社製）を用いて測定した。結果を図１に示す。一方、血中アセトアルデヒド濃度は、Cario Di Padovaらの方法（ALCHOLISM:CLINICAL AND EXPERIMENTAL RESERCH, vol.10,No.1, p86〜89, 1986）に準じて測定した。すなわち、アセトアルデヒドをDNP(2,4-ジニトロフェニルヒドラジン）試薬で誘導体生成後にHPLC（高速液体クロマトグラフィー）を用いて測定した。結果を図２に示す。 [Test Example 1] Alcohol metabolism promoting action (in vivo)
Six-week-old male Wistar rats (body weight 160-170 g) were used. The concentrate of the citrus molasses fermentation product obtained in Example 1 and the Cordyceps extract obtained in Example 2 were used as test substances. As test groups, (1) concentrate 2,000 mg / kg administration group, (2) Cordyceps extract 200 mg / kg + concentrate 2,000 mg / kg administration group, and (3) distilled water administration group (10 mL) as a negative control group / kg) 3 groups (6 animals per group) were set. After fasting for 24 hours, the concentrate solution dissolved in distilled water or distilled water was orally administered to 10 mL / kg body weight. One hour later, 20% (W / V) ethanol was orally administered to a body weight of 10 mL / kg. One hour after ethanol administration, blood was collected from the femoral vein under ether anesthesia. Further, 3 hours after ethanol administration, blood was collected from the posterior vena cava under ether anesthesia. The blood ethanol concentration was measured using F-kit ethanol (Roche Diagnostics). The results are shown in FIG. On the other hand, the blood acetaldehyde concentration was measured according to the method of Cario Di Padova et al. (ALCHOLISM: CLINICAL AND EXPERIMENTAL RESERCH, vol. 10, No. 1, p86-89, 1986). That is, acetaldehyde was measured using HPLC (high performance liquid chromatography) after derivatization with DNP (2,4-dinitrophenylhydrazine) reagent. The results are shown in FIG.

エタノール経口投与１時間後、及び３時間後の血中アルコール濃度は、図１から明らかなように、濃縮物２０００mg/kg投与群、冬虫夏草抽出物２００mg/kg＋濃縮物２０００mg/kg投与群、陰性対照群である蒸留水投与群（１０mL/kg）の間に、統計的な有意差が認められなかった。   As shown in FIG. 1, blood alcohol concentrations 1 hour and 3 hours after oral administration of ethanol were as follows: concentrate 2000 mg / kg administration group, Cordyceps extract 200 mg / kg + concentrate 2000 mg / kg administration group, negative control There was no statistically significant difference between the groups administered with distilled water (10 mL / kg).

一方、エタノール経口投与後の血中アセトアルデヒド濃度については、図２から明らかなように、１時間後においては、濃縮物投与群と対照群との間に統計的有意差はみられないが、濃縮物投与により、血中アセトアルデヒド濃度が低下傾向にあり、これに冬虫夏草抽出物が加わると、血中アセトアルデヒド濃度が有意に低下することが認められる。３時間後においては、濃縮物投与群と対照群との間に差は認められないが、濃縮物＋冬虫夏草抽出物投与群では、なお血中アセトアルデヒド濃度の低下傾向が認められた。   On the other hand, as is clear from FIG. 2, the blood acetaldehyde concentration after oral administration of ethanol does not show a statistically significant difference between the concentrate administration group and the control group after 1 hour. It is observed that the blood acetaldehyde concentration is significantly decreased when the cordyceps extract is added thereto. After 3 hours, no difference was observed between the concentrate administration group and the control group, but the blood acetaldehyde concentration still decreased in the concentrate + Cordyceps extract administration group.

以上の結果から、アルコール経口摂取前に本発明の柑橘糖蜜の発酵産物の濃縮物を経口摂取することにより、血中のエタノール濃度は低下しないが、アセトアルデヒド濃度は低下傾向にあり、該濃縮物とともに冬虫夏草の抽出物を経口摂取すると、アセトアルデヒド濃度の低下が増強され、その低下時間も延長されることが明らかとなった。   From the above results, by orally ingesting the citrus molasses fermentation product concentrate of the present invention before oral intake of alcohol, the ethanol concentration in the blood does not decrease, but the acetaldehyde concentration tends to decrease, together with the concentrate It was clarified that oral extract of Cordyceps sinensis extract enhanced the decrease in acetaldehyde concentration and prolonged the decrease time.

［試験例２］ 柑橘糖蜜の発酵産物の濃縮液がアルコール代謝酵素活性に及ぼす効果
上記動物実験で得られた二日酔い予防効果がどのような作用機序で機能しているかを、in vitroでの酵素反応系（生化学実験講座, タンパク質V, 日本生化学会編, p269-285）を構築して調べた。 [Test Example 2] Effect of concentrated solution of citrus molasses fermented product on alcohol metabolizing enzyme activity The mechanism of hangover prevention obtained in the above animal experiment functions in an in vitro enzyme A reaction system (Biochemical Experiment Course, Protein V, Japanese Biochemical Society, p269-285) was constructed and examined.

アルコール脱水素酵素、アルデヒド脱水素酵素の活性測定は、これらの酵素が反応する際の補酵素、β−ＮＡＤがＮＡＤＨへと変換することを利用した。β−ＮＡＤ、ＮＡＤＨは紫外部の吸収極大波長に違いが見られ、β−ＮＡＤではほとんど見られない３４０nm付近にＮＡＤＨの吸収が見られる。すなわち、３４０nmの紫外部吸収を測定することは、アルコール脱水素酵素、アルデヒド脱水素酵素の酸化還元反応の活性の指標として利用できる。   The activity measurement of alcohol dehydrogenase and aldehyde dehydrogenase utilized the conversion of β-NAD, a coenzyme when these enzymes react, into NADH. β-NAD and NADH have a difference in the absorption maximum wavelength in the ultraviolet region, and absorption of NADH is observed in the vicinity of 340 nm, which is hardly seen in β-NAD. That is, measuring the ultraviolet absorption at 340 nm can be used as an index of the activity of the redox reaction of alcohol dehydrogenase and aldehyde dehydrogenase.

・アルコール脱水素酵素反応液
ピロリン酸ナトリウム（リン酸でpH１０.０調製）３２mM
基質：エタノール３３mM
β−ＮＡＤ２.４mM
酵素溶液：アルコール脱水素酵素（SIGMA, EC1.1.1.1, ウマ肝臓由来,５mUnits/mL )
精製水 ・ Alcohol dehydrogenase reaction solution Sodium pyrophosphate (pH 10.0 prepared with phosphoric acid) 32 mM
Substrate: Ethanol 33mM
β-NAD 2.4 mM
Enzyme solution: Alcohol dehydrogenase (SIGMA, EC1.1.1.1, derived from horse liver, 5mUnits / mL)
purified water

・アルデヒド脱水素酵素反応液
ピロリン酸ナトリウム（リン酸でpH８.０に調製）３２mM
基質：アセトアルデヒド４mM
β−ＮＡＤ４mM
ピラゾール０.１mM
ＥＤＴＡ１mM
酵素溶液：アルデヒド脱水素酵素（SIGMA, EC1.2.1.5, パン酵母由来,０.５ Units/mL)
精製水 Aldehyde dehydrogenase reaction solution Sodium pyrophosphate (adjusted to pH 8.0 with phosphoric acid) 32 mM
Substrate: Acetaldehyde 4 mM
β-NAD4mM
Pyrazole 0.1 mM
EDTA 1mM
Enzyme solution: Aldehyde dehydrogenase (SIGMA, EC1.2.1.5, derived from baker's yeast, 0.5 Units / mL)
purified water

酵素反応液は全量が０.２mLとなるように調製した。基質は最後に添加し、基質添加後速やかに３４０nmの吸光値を測定した。その後、３７℃で１０分反応させた。反応後の３４０nmの吸光値を測定し、吸光値の増加量を算出し、酵素活性の上昇を検討した。アルコール脱水素酵素活性を図３に、アルデヒド脱水素酵素活性を図４にそれぞれ示す。アルコール脱水素酵素反応系に発酵濃縮物を様々な濃度で添加しても、無添加の場合と酵素活性に変化は認められない（図３）。一方アルデヒド脱水素酵素反応系に、発酵濃縮物を様々な濃度で添加すると、アルデヒド脱水素酵素活性が発酵濃縮物の濃度依存的に上昇した。これより、発酵濃縮物は、アルコール脱水素酵素活性には影響せず、アルデヒド脱水素酵素の活性を上昇させる効果があることが明らかとなった。これらの実験結果から、柑橘糖蜜の発酵濃縮物は、アルデヒド脱水素酵素の活性を上昇させることにより、アセトアルデヒドの分解を促進し、結果血中アセトアルデヒド濃度を減衰させることが明らかとなった。   The enzyme reaction solution was prepared so that the total amount was 0.2 mL. The substrate was added last, and the absorbance value at 340 nm was measured immediately after the addition of the substrate. Then, it was made to react at 37 degreeC for 10 minutes. The absorbance value at 340 nm after the reaction was measured, the amount of increase in the absorbance value was calculated, and the increase in enzyme activity was examined. The alcohol dehydrogenase activity is shown in FIG. 3, and the aldehyde dehydrogenase activity is shown in FIG. Even when the fermentation concentrate is added to the alcohol dehydrogenase reaction system at various concentrations, no change is observed in the enzyme activity as compared with the case where it is not added (FIG. 3). On the other hand, when the fermentation concentrate was added to the aldehyde dehydrogenase reaction system at various concentrations, the aldehyde dehydrogenase activity increased depending on the concentration of the fermentation concentrate. From this, it became clear that the fermentation concentrate has an effect of increasing the activity of the aldehyde dehydrogenase without affecting the alcohol dehydrogenase activity. From these experimental results, it became clear that the fermentation concentrate of citrus molasses promotes the decomposition of acetaldehyde by increasing the activity of aldehyde dehydrogenase and consequently attenuates the blood acetaldehyde concentration.

本発明の柑橘糖蜜の発酵濃縮物を経口摂取すると、アルデヒド脱水素酵素活性が増強し、また、冬虫夏草抽出物と併用すると、上記酵素活性がさらに増強するとともに、その持続時間が延長するので、これらを飲酒前に経口摂取すると、二日酔いや悪酔いなどの不快な症状を抑制あるいは軽減させることができる。さらに、アルコール脱水素酵素活性には影響を及ぼさないので、酩酊感（ほろ酔い気分）は妨げないことが期待される。
また、本発明のアルコール代謝促進組成物は、継続的に摂取することによって、アルコール代謝能力を高め、アルコール依存症や、肝臓などの臓器障害の予防にも役立つと考えられる。 When the citrus molasses fermentation concentrate of the present invention is orally ingested, the aldehyde dehydrogenase activity is enhanced, and when used in conjunction with Cordyceps extract, the enzyme activity is further enhanced and the duration thereof is extended. If taken orally before drinking, unpleasant symptoms such as hangover and sickness can be suppressed or reduced. Furthermore, since it does not affect the alcohol dehydrogenase activity, it is expected that the feeling of drunkenness (tipy feeling) will not be disturbed.
In addition, it is considered that the alcohol metabolism promoting composition of the present invention increases the ability of alcohol metabolism by continuously ingesting, and is useful for preventing alcohol dependence and organ damage such as liver.

Claims (16)

柑橘糖蜜をサッカロミセス属酵母を用いてアルコール発酵させて得られる発酵産物の減圧濃縮物。   A reduced-pressure concentrate of a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using Saccharomyces yeast. アルコール発酵が、Ｂｒｉｘ糖度の変化が０．１％以下となるまで発酵させる請求項１記載の発酵産物の減圧濃縮物。   The reduced-pressure concentrate of the fermentation product according to claim 1, wherein the alcoholic fermentation is performed until the Brix sugar content changes to 0.1% or less. 酵母がサッカロミセス セレビシエである請求項１又は２記載の発酵産物の減圧濃縮物。   The reduced-pressure concentrate of the fermentation product according to claim 1 or 2, wherein the yeast is Saccharomyces cerevisiae. 柑橘糖蜜が温州みかん由来である請求項１〜３のいずれか１項記載の発酵産物の減圧濃縮物。   The reduced-pressure concentrate of the fermentation product according to any one of claims 1 to 3, wherein the citrus molasses is derived from Unshu oranges. 請求項１〜４のいずれか１項記載の発酵産物の減圧濃縮物を含有するアルコール代謝促進飲食品。   Alcohol metabolism promotion food / beverage products containing the vacuum concentrate of the fermentation product of any one of Claims 1-4. 発酵産物の減圧濃縮物の有効量が乾燥固形分換算で１〜１０ｇ／ 成人である請求項５記載のアルコール代謝促進飲食品。   The alcohol metabolism-promoting food or drink according to claim 5, wherein the effective amount of the reduced-pressure concentrate of the fermentation product is 1 to 10 g / adult in terms of dry solid content. さらに冬虫夏草抽出物を含有する請求項５又は６記載のアルコール代謝促進飲食品。   Furthermore, the alcohol metabolism promotion food-drinks of Claim 5 or 6 containing Cordyceps extract. 発酵産物の減圧濃縮物と冬虫夏草抽出物の配合割合が、固形分換算で２０〜３０：１〜３である請求項７記載のアルコール代謝促進飲食品。   The alcohol metabolism-promoting food / beverage product according to claim 7, wherein a blending ratio of the reduced-pressure concentrate of the fermentation product and the Cordyceps extract is 20 to 30: 1 to 3 in terms of solid content. アルコール代謝が、アルデヒド脱水素酵素の活性増強によるものである請求項５〜８のいずれか１項記載のアルコール代謝促進飲食品。   Alcohol metabolism promotion food-drinks of any one of Claims 5-8 whose alcohol metabolism is based on the activity enhancement of aldehyde dehydrogenase. 飲食品がドリンク剤である請求項５〜９のいずれか１項記載のアルコール代謝促進飲食品。   The food and drink according to any one of claims 5 to 9, wherein the food or drink is a drink. 請求項１〜４のいずれか１項記載の発酵産物の減圧濃縮物を含有する悪酔い又は二日酔い予防改善用飲食品。   A food or drink for preventing or improving hangover or hangover, comprising the reduced-pressure concentrate of the fermentation product according to any one of claims 1 to 4. 発酵産物の減圧濃縮物の有効量が乾燥固形分換算で１〜１０ｇ／ 成人である請求項１１記載の悪酔い又は二日酔い予防改善用飲食品。   The food / beverage product for preventing or improving hangover or hangover according to claim 11, wherein the effective amount of the reduced-pressure concentrate of the fermentation product is 1 to 10 g / adult in terms of dry solid content. さらに冬虫夏草抽出物を含有する請求項１１又は１２記載の悪酔い又は二日酔い予防改善用飲食品。   The food or drink for improving the prevention of hangover or hangover according to claim 11 or 12, further comprising a cordyceps extract. 発酵産物の減圧濃縮物と冬虫夏草抽出物の配合割合が、固形分換算で２０〜３０：１〜３である請求項１３記載の悪酔い又は二日酔い予防改善用飲食品。   The food / beverage product for preventing or improving hangover or hangover according to claim 13, wherein the blending ratio of the reduced-pressure concentrate of fermented product and Cordyceps extract is 20 to 30: 1 to 3 in terms of solid content. 飲食品がドリンク剤である請求項１１〜１４のいずれか１項記載の悪酔い又は二日酔い予防改善用飲食品。   The food / beverage product for drink prevention improvement of the hangover or hangover prevention of any one of Claims 11-14 which is a drink agent. 柑橘糖蜜をサッカロミセス属酵母を用いてアルコール発酵させて得られる発酵産物５．３％、及び冬虫夏草抽出エキス１．７％を含有する瓶詰飲食品。   A bottled food and drink containing 5.3% of a fermented product obtained by subjecting citrus molasses to alcohol fermentation using Saccharomyces yeast and 1.7% of Cordyceps extract.
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