WO2002000238A1 - Compositions promoting alcohol metabolism - Google Patents

Compositions promoting alcohol metabolism Download PDF

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Publication number
WO2002000238A1
WO2002000238A1 PCT/JP2001/005259 JP0105259W WO0200238A1 WO 2002000238 A1 WO2002000238 A1 WO 2002000238A1 JP 0105259 W JP0105259 W JP 0105259W WO 0200238 A1 WO0200238 A1 WO 0200238A1
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WO
WIPO (PCT)
Prior art keywords
fermentation
alcohol
yeast
hangover
citrus molasses
Prior art date
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PCT/JP2001/005259
Other languages
French (fr)
Japanese (ja)
Inventor
Kenji Mizumoto
Hajime Sasaki
Makoto Yamaguchi
Takaji Yajima
Hideo Hasegawa
Hirofumi Arima
Hideo Otomo
Kenichi Nakazawa
Eiji Negishi
Yasuko Sawai
Masao Takami
Daisuke Kotsutsumi
Masayo Arita
Akitomo Kume
Katsuyuki Uchida
Hajime Tsunoo
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Meiji Dairies Corporation
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Application filed by Meiji Dairies Corporation filed Critical Meiji Dairies Corporation
Priority to AU2001274564A priority Critical patent/AU2001274564A1/en
Priority to JP2002505020A priority patent/JP4852218B2/en
Publication of WO2002000238A1 publication Critical patent/WO2002000238A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56Materials from animals other than mammals
    • A61K35/62Leeches; Worms, e.g. cestodes, tapeworms, nematodes, roundworms, earth worms, ascarids, filarias, hookworms, trichinella or taenia
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, 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
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105Plant extracts, their artificial duplicates or their derivatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/75Rutaceae (Rue family)
    • A61K36/752Citrus, e.g. lime, orange or lemon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/02Antidotes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12GWINE; PREPARATION THEREOF; ALCOHOLIC BEVERAGES; PREPARATION OF ALCOHOLIC BEVERAGES NOT PROVIDED FOR IN SUBCLASSES C12C OR C12H
    • C12G3/00Preparation of other alcoholic beverages
    • C12G3/04Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs
    • C12G3/05Preparation of other alcoholic beverages by mixing, e.g. for preparation of liqueurs with health-improving ingredients, e.g. flavonoids, flavones, polyphenols or polysaccharides
    • C12G3/055Preparation 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

Definitions

  • the present invention relates to an alcohol metabolism promoter composition and a composition for preventing and improving sickness or hangover.
  • Acetaldehyde is highly toxic and can cause gastrointestinal discomfort, nausea, headaches and hangovers. Therefore, it is important to quickly remove acetoaldehyde from blood after alcohol consumption to prevent sickness and hangover. Therefore, it is considered that an oral substance having an action of enhancing the activity of aldehyde dehydrogenase, that is, an oral substance which promotes the metabolism of acetoaldehyde, is effective in preventing or improving the above-mentioned sickness and hangover.
  • Such oral substances include, for example, alcohol metabolism promoters (JP-A-7-285881) containing, as an active ingredient, a peptide having a molecular weight of 200 to 4,000 obtained by enzymatic degradation of corn protein, and pork with protease. Processing And an alcohol metabolism promoting substance containing a processed pork product (JP-A-11-276116), or a hangover-preventive food containing isoflavonoid as an active ingredient (JP-A-2000-7694).
  • alcohol metabolism promoters JP-A-7-285881
  • Processing And an alcohol metabolism promoting substance containing a processed pork product (JP-A-11-276116), or a hangover-preventive food containing isoflavonoid as an active ingredient JP-A-2000-7694.
  • 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 a sickness or hangover prevention improving composition containing the composition as an active ingredient. Disclosure of the invention
  • the present inventors have proposed that a composition obtained by mixing a concentrated solution of an alcoholic fermentation product of citrus molasses with a cordyceps sinensis extract in rats before orally administering ethanol to rats was compared to a control.
  • a composition obtained by mixing a concentrated solution of an alcoholic fermentation product of citrus molasses with a cordyceps sinensis extract in rats before orally administering ethanol to rats was compared to a control.
  • no significant change was observed in the blood ethanol concentration, but it was found that the blood acetoaldehyde concentration was significantly reduced.
  • the mechanism of this result was examined by an enzyme reaction system to which a concentrated solution of an alcohol fermentation product of citrus molasses was added.
  • the concentrate enhanced the activity of aldehyde dehydrogenase.
  • this concentrate has no effect on the activity of alcohol dehydrogenase, and that this concentrate is useful for preventing and improving sickness or hangover.
  • the present invention provides an alcohol metabolism accelerator composition containing a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using a yeast belonging to the genus Saccharomyces, and a composition for preventing and improving sickness or hangover.
  • the present invention also provides an alcohol metabolism promoter composition and a sickness or hangover prevention / improvement composition containing the above-mentioned fermentation product and Cordyceps sinensis extract. Further, the present invention provides the use of the above fermentation product for producing an alcohol metabolism promoter composition and a composition for preventing and improving sickness or hangover.
  • the present invention provides an alcohol metabolism promoter for the fermentation product and cordyceps extract described above.
  • the present invention also provides a composition and a use for producing a composition for preventing or improving hangover or hangover.
  • the present invention provides a method for promoting alcohol metabolism, and a method for preventing or improving sickness or hangover, which comprises 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 sickness or hangover, which comprises administering an effective amount of the above composition and a cordyceps extract.
  • Figure 1 shows that rats were given an oral dose of 2,00 Omg / kg of a concentrate of citrus molasses fermentation product and an oral dose of 200 mg / kg of a cordyceps extract, 200 mg / kg of a concentrate.
  • 4 is a graph showing the effect of subsequent oral ethanol administration on blood alcohol concentration.
  • FIG. 2 is a graph showing the effect on blood acetoaldehyde concentration. *: P ⁇ 0.05 (Student's tes t)
  • FIG. 3 is a graph showing the effect of a concentrate of a fermented product of citrus molasses on alcohol dehydrogenase activity in vitro.
  • FIG. 4 is a graph showing the effect on aldehyde dehydrogenase activity.
  • a method for producing citrus molasses is known (for example, JP-A-10-276578).
  • Juice cake produced when juice is produced by squeezing citrus fruits such as Unshu mandarin oranges contains about 10 to 15% soluble solids and has a high water content.
  • This squeezed lees (including epicarp, pericarp, and carcinoma membrane) was added with slaked lime to facilitate dehydration, limed, and squeezed to obtain Brix 50-
  • the viscous liquid concentrated to 70% is called “citrus molasses”. It also removes insoluble components such as pulp from citrus molasses
  • the soybean is called “depulp citrus molasses", which can also be used in the present invention.
  • citrus fruits examples include, in addition to Unshu mandarin oranges, citrus fruits such as summer oranges, Iyokan, grapefruit, mandarin orange, and lemon;
  • a composition having an alcohol metabolism promoting effect of the present invention can be obtained.
  • Alcohol fermentation of citrus molasses can be performed according to an alcohol fermentation method using molasses as a raw material, which is known to those skilled in the art. Since citrus molasses has a high insoluble pulp content, when used as a food material, it is preferable to dilute so that it can be centrifuged and centrifuge to remove the pulp. This depulpted citrus molasses contains a large amount of sugars that can be assimilated by yeast. Therefore, for the purpose of concentrating active ingredients, depulpted citrus molasses is subjected to alcohol fermentation treatment with yeast, and assimilable sugar in the citrus molasses is converted into ethanol and carbon dioxide to increase the ratio of active ingredients. do.
  • nitrogen sources such as ammonium sulfate, ammonia water, and urea as nutrients, and if necessary, phosphates such as lime superphosphate and ammonium phosphate.
  • yeast the commercially available baker's yeast Saccharomyces cerevisiae is the best, but other yeasts such as .formosens is, S. carl sbergens is, S. el l ipsoideus, S.
  • the composition may also be in the form of a dry powder.
  • Cordyceps is a microorganism belonging to the ascomycetes (Ascomycetes), the ergots (Cl avic ipitales), the ergot fungi (Hypocreaceae) and the cordyceps genus (Cordyceps), and is a microorganism having a complete generation and an incomplete generation.
  • Cordyceps has been prized since ancient times for its fruiting body as a potion for longevity and longevity or as a potion for nutrition and tonicity. In this way, Cordyceps sinensis, which has been prized as a traditional Chinese medicine, is usually obtained by pulverizing the fruit body and taking it.
  • cordyceps for use in the present invention can also use the above fruiting bodies. It is preferable to use an extract obtained by extracting an active ingredient from mycelium with hot water (for example, W096 / 00580 and JP-A-8-12588). It was found that the addition of the extract to the fermentation product of citrus molasses further increased the aldehyde dehydrogenase activity.
  • the operation of culturing and extracting the mycelium of Cordyceps sinensis is a known method (for example, W096 / 00580 and JP-A-8-12588).
  • the cultured mycelium of Cordyceps s inens is added with malt extract, yeast extract, peptone, potato broth, glucose, vitamins, amino acids, nucleic acids, proteins, and, if necessary, host components such as insects. Inoculate the medium and perform liquid or solid culture. For large-scale culture, use liquid culture in an aeration-stirred fermenter (100 to 30 O rpm). Culture is performed at pH 4 to 7, at a culture temperature of 20 to 30 ° C, 3 to 10 days. After completion of the culture, the cultured mycelia are extracted with hot water (85 to: L 00 ° C).
  • extraction may be carried out with water or an aqueous solvent containing a small amount of an acid, base or organic solvent soluble in water. Remove the residue by centrifugation or filtration. The resulting caterpillar fever
  • the water extract may be used as it is in the present invention, or may be concentrated by a conventional method or used as a freeze-dried powder.
  • Cordyceps sinensis extract enhances the enzyme activity is not clear, but Cordyceps sinensis extract has an effect of increasing hepatic blood flow (Food Style 21, vol. 2, No. 5, 1998) and AT in the liver.
  • the action of increasing the amount of P production Jpn. J. PHarmacol., 70: 85-88, 1996) is known. It is considered that the increase in hepatic blood flow by the cordyceps extract promotes the influx of the fermentation product into the liver and increases aldehyde dehydrogenase activity in hepatocytes.
  • the fermented product of 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 to prevent sickness and hangover.
  • Such formulation techniques are well-known to those skilled in the art.
  • the effective dose can not be calculated clearly even if the same amount of alcohol is consumed, and the absorption and metabolism rate is extremely large due to differences in body weight, constitution, etc. i to iog (in terms of dry solids) z It is estimated to be an adult.
  • citrus molasses has been used as a food material for many years, and its safety has been assured by many years of eating experience.
  • the fermented product of the present invention or the fermented product and a cordyceps extract may be used by adding an effective amount thereof directly to food or drink at the time of eating or drinking in order to prevent sickness or hangover.
  • you may process into foods and drinks containing an effective amount. For example, as a drink, sugar 10%, acidity 0.1%, fruit juice 2-3%, flavor 0.1%, fermented product of citrus molasses 5.3%, and cordyceps extract 1.7% And adjust the pH to 3.5-4.0, then heat sterilize at 65 ° C for 10 minutes, then cool and bottle.
  • Foods and drinks may include, in addition to the above, health foods, dietary supplements, and therapeutic foods. Furthermore, in order to reduce bad breath after drinking, foods that have an action to prevent bad breath (For example, green tea polyphenol).
  • foods that have an action to prevent bad breath For example, green tea polyphenol.
  • the depulp molasses was dissolved in warm water.
  • Ammonium sulfate as a nutrient source (nitrogen source), A-Break 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-prepared pulp molasses solution.
  • the preparation solution was adjusted so that the Brix sugar content was 13 ⁇ 1% and the pH was 5 ⁇ 0.2.
  • the amount of depulp molasses in the preparation liquid was 27% (weight).
  • the charge liquid was cooled to 34 ⁇ 4 ° C after batch sterilization (85 ° C, 15 minutes).
  • the prepared solution was inoculated with baker's yeast (0.5%) and fermented.
  • the yeast was inactivated by heating (85 ° C, 15 minutes), and sludge (yeast cells, pulp) contained in the fermentation broth was removed by a fully automatic pressing machine and a filter press. The supernatant was then plate sterilized (134, 3 seconds). Insoluble components generated 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 alcohol metabolism promoting composition (Bri x 45 ⁇ 2%) of the present invention.
  • D medium composition in 1 L: sucrose 40.0 g, K 2 HP0 4 4.0 g, Asuparagin 0.5 g, (NH 4) 2 HP0 4 2.0 g, MgS0 4 ⁇ 7H 2 0 2.0 g, CaC0 3 0.25 g, CaCl 2 0.1 g, yeast extract B-2 4.0 g, pH 5.6
  • 150 L 150 L
  • 15 OmL of the above seed culture solution was inoculated, and the mixture was cultured at 25 ° C, pH 5.5, DO 50%, and stirred at 157 ° C for 3 days. During this time, the generated foam was treated by adding a silicone defoamer.
  • the 150 L culture obtained by the culture was subjected to cell separation treatment using a clarifier to obtain an aqueous suspension of the cells. This was kept at 90 to 95 ° C for 2 hours to perform a heat extraction treatment, followed by clarification by a clarifier to obtain a supernatant. This was filtered using aseptic filters of 0.45 rn and 0.22 zm to obtain 80 L of a pale yellow hot water extract (800 g of solid dry weight).
  • a hangover preventive drink was manufactured using the following ingredients (unit: kg). Concentrate of fermented product of citrus molasses (obtained in Production Example 1): 52.5 Cordyceps extract (obtained in Production Example 2): 16.7 Sugar: 40
  • the bottle was aseptically filled with 12 OmL to obtain a hangover preventive drink.
  • test rats Six-week-old male Wistar rats (weight 160-170 g) were used.
  • the test substance used was the concentrate of the fermented product of citrus molasses obtained in Example 1 and the cordyceps extract obtained in Example 2.
  • test groups (1) Concentrate 2, 000mg / kg administration group, (2) Cordyceps sinensis extract 200 mg / kg + concentrate 2, 000mg / k g administered group, and (3) negative control
  • the blood alcohol concentration at 1 hour and 3 hours after oral administration of ethanol was 200 mg / kg concentrate and 200 mg / kg + concentrate No statistically significant difference was observed between the 200 mg / kg administration group and the distilled water administration group (1 OmL / kg), which was a negative control group.
  • the activity of alcohol dehydrogenase and aldehyde dehydrogenase was measured by utilizing the conversion of coenzyme, 3-NAD, into NADH when these enzymes react.
  • 3— NAD and NADH show a difference in the maximum absorption wavelength in the ultraviolet, and 0—NAD shows NADH absorption near 34 Onm.
  • measuring the ultraviolet absorption at 340 mn can be used as an indicator of the redox activity of alcohol dehydrogenase and aldehyde dehydrogenase.
  • Enzyme solution Alcohol dehydrogenase (SIGMA, EC 1.1.1.1, derived from zebra liver, 5munits / mL)
  • EDTA lmM Enzyme solution Aldehyde dehydrogenase (SIGMA, EC 1. 2.1.5, derived from baker's yeast, 0.5 Units / mL)
  • the enzyme reaction solution was prepared so that the total amount was 0.2 mL.
  • the substrate was added last, and the absorbance at 34 O nm was measured immediately after the addition of the substrate. Thereafter, the reaction was carried out at 37 ° C for 10 minutes.
  • the absorbance at 34 O nm after the reaction was measured, the increase in the absorbance was calculated, and the increase in enzyme activity was examined.
  • Fig. 3 shows the activity of alcohol dehydrogenase
  • Fig. 4 shows the activity of aldehyde dehydrogenase. Even when the fermentation concentrate was added at various concentrations to the alcohol dehydrogenase reaction system, no change was observed in the enzyme activity compared to the case without the addition (Fig. 3).
  • the aldehyde dehydrogenase activity is enhanced, and when used in combination with a Cordyceps sinensis extract, the enzyme activity is further enhanced and the duration is extended. Oral intake before drinking can reduce or reduce unpleasant symptoms such as hangovers and sickness. Furthermore, since it does not affect alcohol dehydrogenase activity, it is expected that it will not hinder drunkenness.
  • the alcohol metabolism-promoting composition of the present invention enhances alcohol metabolism by continuously ingesting the composition, thereby predicting alcohol dependence and organ damage such as liver. It is thought to be useful for prevention

Abstract

Unique compositions promoting alcohol metabolism containing an alcohol fermentation product of citrus molasses optionally mixed with plant worm extract which promotes the aldehyde dehydrogenase activity but exerts substantially no effect on alcohol dehydrogenase activity. Drinks and foods for preventing sick feel from drinking and hangover which contain the above compositions.

Description

明 細 書 アルコール代謝促進剤組成物 技術分野  Description Alcohol metabolism promoter composition Technical field
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。 背景技術  The present invention relates to an alcohol metabolism promoter composition and a composition for preventing and improving sickness or hangover. Background art
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ィ匕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 素酵素系を介してァセトアルデヒドとなり、 ァ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、 ァセトアルデヒ ドが処理しきれなくなり、 血中のァセトアルデヒド濃度が高くなる。 ァセトアル 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ァ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、 ァ 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 (特開平 7-285881) 、 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 (特開平 11- 276116) 、 あるいはイソフラボノィドを有効成分とする二日酔い防止食品 (特開平 2000- 7694) 、 などが提供されている。 Most of the alcohol consumed orally (drinked) is absorbed in the upper gastrointestinal tract and metabolized in the liver, but there is no control mechanism in the liver that regulates alcoholic acidification. Therefore, excessive consumption of alcohol selectively enhances hepatic alcohol metabolism, resulting in large fluctuations in the metabolic system in the liver. Most of the alcohol taken in is converted to acetoaldehyde through the alcohol dehydratase system present in the cytosol of hepatocytes, and acetoaldehyde is further converted to acetic acid by a dehydrogenation reaction by aldehyde dehydrogenase. Is done. If you consume too much alcohol, or if you feel sick and your metabolism of alcohol is delayed, you will not be able to process acetoaldehyde and your blood will have high levels of acetoaldehyde. Acetaldehyde is highly toxic and can cause gastrointestinal discomfort, nausea, headaches and hangovers. Therefore, it is important to quickly remove acetoaldehyde from blood after alcohol consumption to prevent sickness and hangover. Therefore, it is considered that an oral substance having an action of enhancing the activity of aldehyde dehydrogenase, that is, an oral substance which promotes the metabolism of acetoaldehyde, is effective in preventing or improving the above-mentioned sickness and hangover. Such oral substances include, for example, alcohol metabolism promoters (JP-A-7-285881) containing, as an active ingredient, a peptide having a molecular weight of 200 to 4,000 obtained by enzymatic degradation of corn protein, and pork with protease. Processing And an alcohol metabolism promoting substance containing a processed pork product (JP-A-11-276116), or a hangover-preventive food containing isoflavonoid as an active ingredient (JP-A-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。 発明の開示  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 a sickness or hangover prevention improving composition containing the composition as an active ingredient. Disclosure of the invention
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ィヒは認められなかったが、 血中ァ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 こと力、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 proposed that a composition obtained by mixing a concentrated solution of an alcoholic fermentation product of citrus molasses with a cordyceps sinensis extract in rats before orally administering ethanol to rats was compared to a control. However, no significant change was observed in the blood ethanol concentration, but it was found that the blood acetoaldehyde concentration was significantly reduced. The mechanism of this result was examined by an enzyme reaction system to which a concentrated solution of an alcohol fermentation product of citrus molasses was added. The concentrate enhanced the activity of aldehyde dehydrogenase. On the other hand, it has been found that this concentrate has no effect on the activity of alcohol dehydrogenase, and that this concentrate is useful for preventing and improving sickness 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。  That is, the present invention provides an alcohol metabolism accelerator composition containing a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using a yeast belonging to the genus Saccharomyces, and a composition for preventing and improving sickness or hangover.
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。  The present invention also provides an alcohol metabolism promoter composition and a sickness or hangover prevention / improvement composition containing the above-mentioned fermentation product and Cordyceps sinensis extract. Further, the present invention provides the use of the above fermentation product for producing an alcohol metabolism promoter composition and a composition for preventing and improving sickness or hangover.
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。 Further, the present invention provides an alcohol metabolism promoter for the fermentation product and cordyceps extract described above. The present invention also provides a composition and a use for producing a composition for preventing or improving hangover or hangover.
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。 図面の簡単な説明  Furthermore, the present invention provides a method for promoting alcohol metabolism, and a method for preventing or improving sickness or hangover, which comprises 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 sickness or hangover, which comprises administering an effective amount of the above composition and a cordyceps extract. BRIEF DESCRIPTION OF THE FIGURES
図 1は、 ラットに対する、 柑橘糖蜜の発酵産物の濃縮物 2 , 0 0 O mg/kg経口投 与、 及び冬虫夏草抽出物 2 0 0 mg/kg+濃縮物 2 0 0 O mg/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。  Figure 1 shows that rats were given an oral dose of 2,00 Omg / kg of a concentrate of citrus molasses fermentation product and an oral dose of 200 mg / kg of a cordyceps extract, 200 mg / kg of a concentrate. 4 is a graph showing the effect of subsequent oral ethanol administration on blood alcohol concentration.
図 2は、 同じく、 血中ァ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 . 0 5 (Student ' s tes t)  FIG. 2 is a graph showing the effect on blood acetoaldehyde concentration. *: P <0.05 (Student's tes t)
図 3は、 in vi tro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。  FIG. 3 is a graph showing the effect of a concentrate of a fermented product of citrus molasses on alcohol dehydrogenase activity in vitro.
図 4は、 同じく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。 発明を実施するための最良の形態  FIG. 4 is a graph showing the effect on aldehyde dehydrogenase activity. BEST MODE FOR CARRYING OUT THE INVENTION
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 1 0〜1 5 %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、 B r i x 5 0〜7 0 %に濃縮した粘ちよう状の液は、 「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。 A method for producing citrus molasses is known (for example, JP-A-10-276578). Juice cake produced when juice is produced by squeezing citrus fruits such as Unshu mandarin oranges contains about 10 to 15% soluble solids and has a high water content. This squeezed lees (including epicarp, pericarp, and carcinoma membrane) was added with slaked lime to facilitate dehydration, limed, and squeezed to obtain Brix 50- The viscous liquid concentrated to 70% is called "citrus molasses". It also removes insoluble components such as pulp from citrus molasses The soybean is called "depulp citrus molasses", which can also be used in the present 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、 あるいはュズ、 力ボス、 スダ チ、 ダイダイ、 サンボウカンなどが含まれる。  Examples of the citrus fruits include, in addition to Unshu mandarin oranges, citrus fruits such as summer oranges, Iyokan, grapefruit, mandarin orange, and lemon;
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、 血中ァ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、 該発酵産物がァ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 is orally ingested before alcohol consumption, blood acetoaldehyde is decreased. And it became clear that this phenomenon was based on the action of the fermentation product to increase the activity of acetoaldehyde metabolizing enzyme. In other words, it was revealed that the composition comprising the fermented product of citrus molasses was effective for sickness 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一ル発酵法に準じて行うことができる。 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。  By subjecting citrus molasses to alcohol fermentation using yeast, a composition having an alcohol metabolism promoting effect of the present invention can be obtained. Alcohol fermentation of citrus molasses can be performed according to an alcohol fermentation method using molasses as a raw material, which is known to those skilled in the art. Since citrus molasses has a high insoluble pulp content, when used as a food material, it is preferable to dilute so that it can be centrifuged and centrifuge to remove the pulp. This depulpted citrus molasses contains a large amount of sugars that can be assimilated by yeast. Therefore, for the purpose of concentrating active ingredients, depulpted citrus molasses is subjected to alcohol fermentation treatment with yeast, and assimilable sugar in the citrus molasses is converted into ethanol and carbon dioxide to increase the ratio of active ingredients. do.
脱パルプ柑橘糖蜜を水で希釈して、 糖度を 1 0〜2 0 %程度に調整する。 栄養 源として硫酸アンモニゥム、 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、 リン酸アンモニゥ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 (6 0 °Cで 3 0分、 あるいは 8 5でで1 5分) する。 冷却 (3 0 〜3 5 °C) した後、 酵母を加えアルコール発酵させる。 発酵温度は、 2 7土 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、 . f ormosens i s , S. car l sbergens i s、 S. el l ipsoideus, S. rouxi i, あるいは . sakeなども用いてみてもよい。 発酵が進むにつれて、 B r i x糖度は低下する。 発酵終了は、 3 0分経過時の B r i x糖度変化が 0 . 1 %以下を目安とする。 発酵産物は、 粘ちよう度が低下 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。 Dilute the depulpted citrus molasses with water to adjust the sugar content to about 10 to 20%. Add nitrogen sources such as ammonium sulfate, ammonia water, and urea as nutrients, and if necessary, phosphates such as lime superphosphate and ammonium phosphate. Adjust the pH to approximately 5 and sterilize by heating (30 minutes at 60 ° C or 15 minutes at 85). After cooling (30-35 ° C), yeast is added and alcohol fermentation is performed. The fermentation temperature is 27--7. As the yeast, the commercially available baker's yeast Saccharomyces cerevisiae is the best, but other yeasts such as .formosens is, S. carl sbergens is, S. el l ipsoideus, S. rouxi i, or. You may try using it. As fermentation progresses, Brix sugar content decreases. The end of fermentation should be about 0.1% or less in Brix sugar content after 30 minutes. The fermented product has a reduced stickiness, and it is possible to further concentrate the active ingredient. The concentrated solution undergoes the steps of cell separation, clarification, sterilization, concentration, and re-sterilization, and finally, the alcohol metabolism promoting composition of the present invention is obtained. The composition may also be in the form of a dry powder.
冬虫夏草は、 子嚢菌類 (Ascomycetes) 、 麦角菌目 (Cl avic ipi t ales) 、 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 is a microorganism belonging to the ascomycetes (Ascomycetes), the ergots (Cl avic ipitales), the ergot fungi (Hypocreaceae) and the cordyceps genus (Cordyceps), and is a microorganism having a complete generation and an incomplete generation. Cordyceps has been prized since ancient times for its fruiting body as a potion for longevity and longevity or as a potion for nutrition and tonicity. In this way, Cordyceps sinensis, which has been prized as a traditional Chinese medicine, is usually obtained by pulverizing the fruit body and taking it.
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 s inens i s (Berk. ) Saccや Cordyceps mi l i t ar i s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 W096/00580及び特開平 8- 12588号) を用いるのがよい。 該抽出物を 柑橋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 W096/00580及び特開平 8- 12588号) である。  It is considered that the cordyceps for use in the present invention can also use the above fruiting bodies. It is preferable to use an extract obtained by extracting an active ingredient from mycelium with hot water (for example, W096 / 00580 and JP-A-8-12588). It was found that the addition of the extract to the fermentation product of citrus molasses further increased the aldehyde dehydrogenase activity. The operation of culturing and extracting the mycelium of Cordyceps sinensis is a known method (for example, W096 / 00580 and JP-A-8-12588).
すなわち、 Cordyceps s inens i sの培養菌子体を、 麦芽エキス、 酵母エキス、 ぺ 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 (1 0 0〜3 0 O rpm) による 液体培養を用いる。 培養は、 pH 4〜 7、 培養温度 2 0〜 3 0 °C、 3〜; 1 0日間行 う。 培養終了後、 培養菌子体を熱水 (8 5〜: L 0 0 °C) 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, the cultured mycelium of Cordyceps s inens is added with malt extract, yeast extract, peptone, potato broth, glucose, vitamins, amino acids, nucleic acids, proteins, and, if necessary, host components such as insects. Inoculate the medium and perform liquid or solid culture. For large-scale culture, use liquid culture in an aeration-stirred fermenter (100 to 30 O rpm). Culture is performed at pH 4 to 7, at a culture temperature of 20 to 30 ° C, 3 to 10 days. After completion of the culture, the cultured mycelia are extracted with hot water (85 to: L 00 ° C). Alternatively, extraction may be carried out with water or an aqueous solvent containing a small amount of an acid, base or organic solvent soluble in water. Remove the residue by centrifugation or filtration. The resulting caterpillar fever The water extract may be used as it is in the present invention, or 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、 血中ァセトアルデヒ 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ァセ 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 AT P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、 肝細胞内のァ 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 AT Pより 合成されることから、 AT P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。  Ingestion of fermented citrus molasses prior to alcohol consumption lowers blood acetoaldehyde. In addition, ingestion of the fermentation product and cordyceps extract further lowers blood acetate aldehyde. That is, when a fermented product of citrus molasses or a mixed composition of the fermented product and a cordyceps extract is obtained, the effect of preventing and improving sickness and hangover is obtained. This preventive effect is based on the action of the fermented product of citrus molasses to increase the activity of aldehyde dehydrogenase, as described above. Cordyceps extract does not show any activity to increase the activity of aldehyde dehydrogenase. The reason why Cordyceps sinensis extract enhances the enzyme activity is not clear, but Cordyceps sinensis extract has an effect of increasing hepatic blood flow (Food Style 21, vol. 2, No. 5, 1998) and AT in the liver. The action of increasing the amount of P production (Jpn. J. PHarmacol., 70: 85-88, 1996) is known. It is considered that the increase in hepatic blood flow by the cordyceps extract promotes the influx of the fermentation product into the liver and increases aldehyde dehydrogenase activity in hepatocytes. In addition, the action of aldehyde dehydrogenase requires the coenzyme NAD, and NAD is synthesized from nicotinic acid and ATP. However, 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。  Analysis of the components that enhance aldehyde dehydrogenase activity in the fermented product of citrus molasses revealed that some components were contained, but the effective concentrations of these components and the content in the fermented product were taken into account. Then, the action of the fermentation product cannot be explained by the action of each of these components. Further, a composition in which these components are mixed in the content ratio of the fermentation product cannot explain the effect of the fermentation product. As a result, the action of the fermentation product to enhance the activity of aldehyde dehydrogenase is considered to be based on the combined action of the components containing the fermentation product.
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ァ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、 というュニー クな作用が得られる。 It is considered preferable to ingest the fermented product of citrus molasses or the mixed composition of the fermented product and the cordyceps extract before alcohol consumption. It can be expected to reduce sickness and hangover even after or after alcohol consumption. By ingesting the composition in advance, the activity of aldehyde dehydrogenase is increased, and the harmful blood acetoaldehyde caused by drinking is reduced, while the activity of alcohol dehydrogenase is substantially reduced. It has a unique effect of preventing sickness and hangovers without disturbing the "drinking mood" 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、 ァ 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 i〜i o g (乾燥固形分換算) z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 product of 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 to prevent sickness and hangover. Such formulation techniques are well-known to those skilled in the art. The effective dose can not be calculated clearly even if the same amount of alcohol is consumed, and the absorption and metabolism rate is extremely large due to differences in body weight, constitution, etc. i to iog (in terms of dry solids) z It is estimated to be an adult. Regarding toxicity, citrus molasses has been used as a food material for many years, and its safety has been assured by many 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 1 0 %、 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、 6 5 °Cで 1 0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ァ-リノレン酸及び Z又はァ ラキドン酸カスケ一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。  Further, the fermented product of the present invention, or the fermented product and a cordyceps extract may be used by adding an effective amount thereof directly to food or drink at the time of eating or drinking in order to prevent sickness or hangover. Moreover, you may process into foods and drinks containing an effective amount. For example, as a drink, sugar 10%, acidity 0.1%, fruit juice 2-3%, flavor 0.1%, fermented product of citrus molasses 5.3%, and cordyceps extract 1.7% And adjust the pH to 3.5-4.0, then heat sterilize at 65 ° C for 10 minutes, then cool and bottle. In addition, it is conceivable that aralinolenic acid and Z or arachidonic acid cascade, which have an effect of improving fatty acid metabolism, are added to the drink to supplement the liver lipid metabolism. Similarly, it may be combined with other functional drinks, foods for specified health use, and the like.
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 (例えば緑茶ポリフエノール) を併用してもよい。 Foods and drinks may include, in addition to the above, health foods, dietary supplements, and therapeutic foods. Furthermore, in order to reduce bad breath after drinking, foods that have an action to prevent bad breath (For example, green tea polyphenol).
柑橘糖蜜の発酵産物に冬虫夏草抽出物を添加 (配合) する塲合は、 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。  Babaai is a fermented product of citrus molasses with a cordyceps extract added (blended). Its composition ratio (weight) is fermented product: cordyceps extract = 20-30: approx. 1-3 (solid content conversion) However, since the optimum mixing ratio can be easily determined by a person skilled in the art by further experiments, the mixing ratio thus determined is also included in the present invention. It is preferable that the obtained mixed composition is 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; Alcohol and Aldehyde metabolizing system- IV: p.109, 1980) 。 アミノ酸としては、 例 えば、 グリシン、 L-ァスパラギン酸、 L-システィン、 L -セリン、 L-ァラニ ン、 L-メチォニンなどが挙げられる。 実施例  In addition to the mixed composition of the fermented product of the present invention and the Cordyceps sinensis extract, an amino acid may be further contained. Incorporation of amino acids can supplement the inhibitory effect of alcohol on absorption in the stomach and intestine and promotes alcohol metabolism by participating in the NAD system (Biol. PHarm. Bull., 18 (12): 1653-1656, 1995; Alcohol and Aldehyde metabolizing system-IV: p.109, 1980). Examples of the amino acids include glycine, L-aspartic acid, L-cystine, L-serine, L-aranin, L-methionine and the like. Example
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。  Hereinafter, the present invention will be described specifically with reference to Examples and Test Examples, but the present invention is not limited to these Examples.
[実施例 1 ] 柑橘糖蜜の発酵産物の濃縮  [Example 1] Concentration of fermented product of citrus molasses
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 B r i x糖度 40〜50 %まで循環濃縮して柑橘糖蜜 50 kg (B r i x45% pH8〜9) を得た。 柑橘糖蜜は、 使用時まで冷凍保管した。  1000 kg of Unshu mandarin orange was squeezed with an in-line juicer to obtain 500 kg of fruit juice and 500 kg of juice residue. Slaked lime was added to about 500 kg of the juice residue (about 0.3%), and after lining, pressed, 250 kg of juice and 250 kg of juice cake were obtained. This juice was circulated and concentrated to a Brix sugar content of 40 to 50% to obtain 50 kg of citrus molasses (Brix45% pH8 to 9). Citrus molasses was stored frozen until use.
この柑橘糖蜜を解凍し、 クェン酸で pH調整 (pH6. 0 ± 0. 5、 1 0土 5°C) 後、 熱水で希釈 (50°C以上、 B r i X 1 0 ± 5 %) し、 遠心分離 Thaw the citrus molasses, adjust the pH with citric acid (pH 6.0 ± 0.5, 10 soil 5 ° C), and dilute with hot water (50 ° C or more, Bri X 10 ± 5%). , Centrifugation
(5100G) して不溶性成分 ひ \°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°C · 1 5秒保持) した後、 プレート式濃縮機で濃縮し、 10°C以下に冷却した。 B r i X調整 (B r i X 50土 1 %、 パルプ 20 %以 下、 pH 6.0 ± 1 ) を脱パルプ糖蜜 37 kg得た。 (5100G) to remove the insoluble component (Hg). Molasses from which pulp has been removed After plate sterilization (hold at 88 ° C for 15 seconds), the mixture was concentrated with a plate concentrator and cooled to 10 ° C or less. 37 kg of Brix preparation (BriX 50 soil 1%, pulp 20% or less, pH 6.0 ± 1) was obtained from depulp molasses.
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ゥム、 消泡剤としてァヮブレーク G-109、 pH調整剤としてクェン酸を、 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 B r i x 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°C、 15分) 後、 34±4°C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、 B r i X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 B r i x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°C、 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で、 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一で除去後、 減圧濃縮し た。 この濃縮物は再殺菌 (8°C、 30秒) 後冷却して、 本発明のアルコ一ル代謝 促進組成物 (B r i x45±2%) 10kgを得た。  The depulp molasses was dissolved in warm water. Ammonium sulfate as a nutrient source (nitrogen source), A-Break 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-prepared pulp molasses solution. The preparation solution was adjusted so that the Brix sugar content was 13 ± 1% and the pH was 5 ± 0.2. The amount of depulp molasses in the preparation liquid was 27% (weight). The charge liquid was cooled to 34 ± 4 ° C after batch sterilization (85 ° C, 15 minutes). The prepared solution was inoculated with baker's yeast (0.5%) and fermented. Yeast assimilates sugar contained in depulp citrus molasses to generate carbon dioxide gas, and as the fermentation proceeds, the Brix sugar content and pH decrease. Fermentation time is about 5-6 hours. The end of fermentation is to be used when the change in Brix sugar content after 30 minutes is 0.1% or less. After completion of the fermentation, the yeast was inactivated by heating (85 ° C, 15 minutes), and sludge (yeast cells, pulp) contained in the fermentation broth was removed by a fully automatic pressing machine and a filter press. The supernatant was then plate sterilized (134, 3 seconds). Insoluble components generated 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 alcohol metabolism promoting composition (Bri x 45 ± 2%) of the present invention.
[実施例 2] 冬虫夏草抽出物の製造  [Example 2] Production of Cordyceps sinensis extract
M20 Y2培地 15 OmLを 50 OmL容三角フラスコに採りオートクレ一ブ滅菌 した。 この培地に、 Cordyceps sinensis MF-20008 (FERM BP-51 9) の凍結保存 菌糸体 lmLを接種し、 25°C、 180 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。  15 OmL of M20 Y2 medium was placed in a 50 OmL Erlenmeyer flask and sterilized by autoclaving. The medium was inoculated with 1 mL of cryopreserved mycelium of Cordyceps sinensis MF-20008 (FERM BP-519) and cultured with shaking at 180 at 25 ° C for 5 days. Using this as a seed bacterium, a 150 L large-scale culture was performed as follows.
D培地 (1 L中の組成:蔗糖 40.0 g、 K2HP044.0 g、 ァスパラギン 0.5 g、 (NH4) 2HP042.0 g、 MgS04 · 7H20 2.0 g、 CaC03 0.25 g、 CaCl20.1 g、 酵母エキス B- 2 4.0 g、 pH5.6) 150 Lを、 150 Lフアーメン夕一 に無菌濾過処理後投入し、 上記の種培養液 1 5 OmLを接種し、 25°C、 pH 5.5、 DO 50%に制御し、 157ΠΜ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°C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 0.45 rn, 及び 0.22 zm無菌フィルターを用い濾過し、 淡黄色の熱水抽出 液 80 L (固形物乾燥重量 800 g) を得た。 D medium (composition in 1 L: sucrose 40.0 g, K 2 HP0 4 4.0 g, Asuparagin 0.5 g, (NH 4) 2 HP0 4 2.0 g, MgS0 4 · 7H 2 0 2.0 g, CaC0 3 0.25 g, CaCl 2 0.1 g, yeast extract B-2 4.0 g, pH 5.6) 150 L, 150 L Then, 15 OmL of the above seed culture solution was inoculated, and the mixture was cultured at 25 ° C, pH 5.5, DO 50%, and stirred at 157 ° C for 3 days. During this time, the generated foam was treated by adding a silicone defoamer. The 150 L culture obtained by the culture was subjected to cell separation treatment using a clarifier to obtain an aqueous suspension of the cells. This was kept at 90 to 95 ° C for 2 hours to perform a heat extraction treatment, followed by clarification by a clarifier to obtain a supernatant. This was filtered using aseptic filters of 0.45 rn and 0.22 zm to obtain 80 L of a pale yellow hot water extract (800 g of solid dry weight).
[実施例 3 ] 二日酔い予防ドリンク剤の製造  [Example 3] Production of hangover preventive drink
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  A hangover preventive drink was manufactured using the following ingredients (unit: kg). Concentrate of fermented product of citrus molasses (obtained in Production Example 1): 52.5 Cordyceps extract (obtained in Production Example 2): 16.7 Sugar: 40
果汁 : 100  Fruit juice: 100
ァスコルビン酸 : 1  Ascorbic acid: 1
クェン酸 : 3  Cuenoic acid: 3
香料 : 4  Fragrance: 4
水 : 782. 8 今量 1000  Water: 782.8 Amount now 1000
上記を溶解し 95°Cで 20分間殺菌した後、 ビンに無菌的に 12 OmLづっ充填 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 12 OmL to obtain a hangover preventive drink.
[試験例 1] アルコール代謝促進作用 (in vivo)  [Test Example 1] Alcohol metabolism promoting effect (in vivo)
6週齢の雄性ウィスター系ラット (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 (1 0 mL/kg) の 3群 (1群 6匹) を設定した。 2 4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 1 O mL/kg体重となる ように経口投与した。 その 1時間後に、 2 0 % (W/V) エタノールを 1 O mL/kg 体重となるように経口投与した。 ェタノ一ル投与 1時間後にエーテル麻酔下で大 腿静脈より採血した。 さらにエタノ一ル投与 3時間後にェ一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キットェタノ一ル (ロシュ ·ダイァ 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、 血中ァセ トアルデヒド濃度は、 Car i o Di Padovaらの方法 (ALCHOL I SM : CL INICAL AND EXPERIMENTAL RESERCH, vol . ΙΟ, Νο. 1 , p86〜89, 1986) に準じて測定した。 す なわち、 ァセトアルデヒドを DNP (2, 4 ジニトロフエニルヒドラジン) 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。 Six-week-old male Wistar rats (weight 160-170 g) were used. The test substance used was the concentrate of the fermented product of citrus molasses obtained in Example 1 and the cordyceps extract obtained in Example 2. As test groups, (1) Concentrate 2, 000mg / kg administration group, (2) Cordyceps sinensis extract 200 mg / kg + concentrate 2, 000mg / k g administered group, and (3) negative control Three groups (six per group) of distilled water administration group (10 mL / kg) were set. After a 24-hour fast, a concentrated solution dissolved in distilled water or distilled water was orally administered to a concentration of 1 OmL / kg body weight. One hour later, 20% (W / V) ethanol was orally administered to a concentration of 1 OmL / kg body weight. One hour after administration of ethanol, blood was collected from the femoral vein under ether anesthesia. Further, 3 hours after administration of ethanol, blood was collected from the posterior large vein under ether anesthesia. The blood ethanol concentration was measured using F kit ethanol (Roche Diagnostics). The results are shown in Figure 1. On the other hand, the blood acetoaldehyde concentration was measured according to the method of Cario Di Padova et al. That is, acetoaldehyde was measured by HPLC (high-performance liquid chromatography) after generating the derivative with DNP (2,4-dinitrophenylhydrazine) reagent. The result is shown in figure 2.
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 2 0 0 O mg/kg投与群、 冬虫夏草抽出物 2 0 0 mg/kg+ 濃縮物 2 0 0 O mg/kg投与群、 陰性対照群である蒸留水投与群 ( 1 O mL/kg) の間 に、 統計的な有意差が認められなかった。  The blood alcohol concentration at 1 hour and 3 hours after oral administration of ethanol was 200 mg / kg concentrate and 200 mg / kg + concentrate No statistically significant difference was observed between the 200 mg / kg administration group and the distilled water administration group (1 OmL / kg), which was a negative control group.
一方、 エタノール経口投与後の血中ァ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、 血中ァ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、 血中ァ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、 なお血中ァセ卜 アルデヒド濃度の低下傾向が認められた。  On the other hand, as shown in Figure 2, there was no statistically significant difference in the concentration of acetoaldehyde in the blood after oral administration of ethanol between the group receiving the concentrate and the control group after 1 hour. However, administration of the concentrate tends to lower the blood acetaldehyde concentration, and the addition of the cordyceps extract to this significantly lowers the blood acetaldehyde concentration. After 3 hours, no difference was observed between the concentrate-administered group and the control group. However, in the group administered with the concentrate and the Cordyceps sinensis extract, the blood acetate aldehyde concentration still tended to decrease.
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、 ァセトァ 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、 ァ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 ingesting the concentrate of the fermented product of citrus molasses of the present invention orally before ingestion of alcohol, the ethanol concentration in the blood does not decrease, but the acetoaldehyde concentration tends to decrease. Oral intake of cordyceps extract Then, it became clear that the decrease of the acetoaldehyde concentration was enhanced and the decrease time was prolonged.
[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  [Test Example 2] Effect of concentrated solution of fermented product of citrus molasses on alcohol metabolizing enzyme activity
上記動物実験で得られたニ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。  The mechanism of the function of the preventive effect of hangover obtained in the above-mentioned animal experiments was determined by the in vitro enzyme reaction system (Biochemical Experiment Course, Protein V, edited by The Japanese Biochemical Society, p. 269). -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、 ]3— NADが NADHへと変換することを利用した。 ]3— NAD、 NADHは紫外部の吸収極大波長に違いが見られ、 0— NADではほと んど見られない 34 Onm付近に NADHの吸収が見られる。 すなわち、 340mn 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 of alcohol dehydrogenase and aldehyde dehydrogenase was measured by utilizing the conversion of coenzyme, 3-NAD, into NADH when these enzymes react. ] 3— NAD and NADH show a difference in the maximum absorption wavelength in the ultraviolet, and 0—NAD shows NADH absorption near 34 Onm. In other words, measuring the ultraviolet absorption at 340 mn can be used as an indicator of the redox activity of alcohol dehydrogenase and aldehyde dehydrogenase.
•アルコール脱水素酵素反応液  • Alcohol dehydrogenase reaction solution
ピロリン酸ナトリゥム (リン酸で pH 10.0調製) 32mM  Sodium sodium pyrophosphate (pH 10.0 adjusted with phosphoric acid) 32mM
基質:エタノール 33mM  Substrate: 33 mM ethanol
β一 NAD 2.4mM  β-1 NAD 2.4mM
酵素溶液:アルコール脱水素酵素 (SIGMA, EC1.1.1.1, ゥマ肝臓由来, 5mU nits/mL )  Enzyme solution: Alcohol dehydrogenase (SIGMA, EC 1.1.1.1, derived from zebra liver, 5munits / mL)
精製水  purified water
•アルデヒド脱水素酵素反応液  • Aldehyde dehydrogenase reaction solution
ピ口リン酸ナトリウム (リン酸で pH 8.0に調製) 32 mM  Sodium phosphate mouth (pH adjusted to 8.0 with phosphoric acid) 32 mM
基質:ァセトアルデヒド 4 mM  Substrate: Acetaldehyde 4 mM
β -NAD mM  β-NAD mM
ピラゾール 0. ImM  Pyrazole 0. ImM
EDTA lmM 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 Uni t s/mL) EDTA lmM Enzyme solution: Aldehyde dehydrogenase (SIGMA, EC 1. 2.1.5, derived from baker's yeast, 0.5 Units / mL)
精製水  purified water
酵素反応液は全量が 0 . 2 mL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 3 4 O nmの吸光値を測定した。 その後、 3 7 °Cで 1 0分反応さ せた。 反応後の 3 4 O nm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、 ァセ トアルデヒドの分解を促進し、 結果血中ァ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。 産業上の利用可能性  The enzyme reaction solution was prepared so that the total amount was 0.2 mL. The substrate was added last, and the absorbance at 34 O nm was measured immediately after the addition of the substrate. Thereafter, the reaction was carried out at 37 ° C for 10 minutes. The absorbance at 34 O nm after the reaction was measured, the increase in the absorbance was calculated, and the increase in enzyme activity was examined. Fig. 3 shows the activity of alcohol dehydrogenase, and Fig. 4 shows the activity of aldehyde dehydrogenase. Even when the fermentation concentrate was added at various concentrations to the alcohol dehydrogenase reaction system, no change was observed in the enzyme activity compared to the case without the addition (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 in a concentration-dependent manner of the fermentation concentrate. From this, it was clarified that the fermented concentrate had no effect on alcohol dehydrogenase activity and had an effect of increasing the activity of aldehyde dehydrogenase. From these experimental results, it is clear that the fermented concentrate of citrus molasses promotes the degradation of acetoaldehyde by increasing the activity of aldehyde dehydrogenase, thus attenuating the blood acetoaldehyde concentration. It became. Industrial applicability
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。  When the fermented concentrate of citrus molasses of the present invention is orally ingested, the aldehyde dehydrogenase activity is enhanced, and when used in combination with a Cordyceps sinensis extract, the enzyme activity is further enhanced and the duration is extended. Oral intake before drinking can reduce or reduce unpleasant symptoms such as hangovers and sickness. Furthermore, since it does not affect alcohol dehydrogenase activity, it is expected that it will not hinder drunkenness.
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つ 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 The alcohol metabolism-promoting composition of the present invention enhances alcohol metabolism by continuously ingesting the composition, thereby predicting alcohol dependence and organ damage such as liver. It is thought to be useful for prevention

Claims

請求の範囲 The scope of the claims
1. 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。 1. An alcohol metabolism promoter composition containing a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using yeast of the genus Saccharomyces.
2. アルコール発酵が、 B r i x糖度の変化が 0. 1%以下となるまで発酵さ せる請求項 1記載のアルコール代謝促進剤組成物。  2. The alcohol metabolism promoter composition according to claim 1, wherein the alcohol fermentation is performed until the change in Brix sugar content becomes 0.1% or less.
3. 酵母がサッカロミセス セレピシェである請求項 1又は 2記載のアルコ一 ル代謝促進剤組成物。  3. The alcohol metabolism promoter composition according to claim 1, wherein the yeast is Saccharomyces cerevisiae.
4. 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項記載のアル コール代謝促進剤組成物。  4. The alcohol metabolism promoter composition according to any one of claims 1 to 3, wherein the citrus molasses is derived from Unshu mandarin orange.
5. さらに冬虫夏草抽出物を含有する請求項;!〜 4のいずれかに記載のアルコ ール代謝促進剤組成物。  5. A claim further comprising a cordyceps extract; 5. The alcohol metabolism promoter composition according to any one of items 4 to 4.
6. 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 1〜 5のいずれか 1項記載のアルコール代謝促進剤組成物。  6. The alcohol metabolism promoter composition according to any one of claims 1 to 5, wherein the alcohol metabolism is due to enhancement of the activity of aldehyde dehydrogenase.
7. 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悪酔い又は二日酔い予防改善剤組成物。  7. A sickness or hangover prevention / improvement composition containing a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using Saccharomyces yeast.
8. アルコール発酵が、 B r i x糖度の変化が 0. 1%以下となるまで発酵さ せる請求項 7記載の悪酔い又は二日酔い予防改善剤組成物。  8. The composition for preventing or improving sickness or hangover according to claim 7, wherein the fermentation is performed by alcohol fermentation until the change in Brix sugar content becomes 0.1% or less.
9. 酵母がサッカロミセス セレピシェである請求項 7又は 8記載の悪酔い又 は二日酔い予防改善剤組成物。  9. The composition for preventing or improving sickness or hangover according to claim 7 or 8, wherein the yeast is Saccharomyces cerevisiae.
10. 柑橘糖蜜が温州みかん由来である請求項 7〜 9のいずれか 1項記載の悪 酔い又は二日酔い予防改善剤組成物。  10. The composition for preventing or improving a sickness or hangover according to any one of claims 7 to 9, wherein the citrus molasses is derived from Unshu mandarin orange.
11. さらに冬虫夏草抽出物を含有する請求項 7〜 10のいずれかに記載の悪 酔い又は二日酔い予防改善剤組成物。  11. The composition for preventing or improving sickness or hangover according to any one of claims 7 to 10, further comprising a cordyceps extract.
12. 請求項 1〜 6のいずれか 1項記載の組成物を含有するアルコール代謝促 12. Promoting alcohol metabolism containing the composition according to any one of claims 1 to 6.
1 3 . 飲食品がドリンク剤である請求項 1 2に記載のアルコール代謝促進飲食13. The food or beverage for promoting alcohol metabolism according to claim 12, wherein the food or drink is a drink.
PP
PPo PPo
1 4. 請求項 1〜 6のいずれか 1項記載の組成物を含有する悪酔い又は二日酔 い予防改善用飲食品。  1 4. A food or drink for preventing or improving sickness or hangover, comprising the composition according to any one of claims 1 to 6.
1 5 . 飲食品がドリンク剤である請求項 1 4記載の悪酔い又は二日酔い予防改 善用飲食品。  15. The food or drink for preventing or improving sickness or hangover according to claim 14, wherein the food or drink is a drink.
1 6 . 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 る発酵産物のアルコ一ル代謝促進剤組成物製造のための使用。  16. Use of a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using Saccharomyces yeast to produce an alcohol metabolism promoter composition.
1 7 . 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 る発酵産物及び冬虫夏草抽出物のアルコール代謝促進剤組成物製造のための使 用。  17. Use of a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using Saccharomyces yeast and a cordyceps summer extract to produce an alcohol metabolism promoter composition.
1 8 . 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。  18. Use of a fermentation product obtained by subjecting citrus molasses to alcohol fermentation using yeast of the genus Saccharomyces for the production of a composition for preventing and improving sickness or hangover.
1 9 . 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 る発酵産物及び冬虫夏草抽出物の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。  1 9. Use of a fermented product obtained by alcoholic fermentation of citrus molasses using yeast of the genus Saccharomyces and an extract of Cordyceps sinensis for the manufacture of a composition for preventing and improving sickness or hangover.
2 0 . 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 る発酵産物のアルコール代謝促進飲食品製造のための使用。  20. Use of a fermentation product obtained by alcoholic fermentation of citrus molasses with yeast of the genus Saccharomyces for the production of foods and beverages for promoting alcohol metabolism.
2 1 . 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 る発酵産物及び冬虫夏草抽出物のアルコール代謝促進飲食品製造のための使用。  21. Use of a fermented product obtained by subjecting citrus molasses to alcohol fermentation with yeast of the genus Saccharomyces and a cordyceps extract for the production of foods and drinks for promoting alcohol metabolism.
2 2 . 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 る発酵産物の悪酔い又は二日酔い予防改善用飲食品製造のための使用。  22. Use of a fermented product obtained by alcoholic fermentation of citrus molasses with yeast of the genus Saccharomyces for the production of foods and drinks for preventing and improving sickness or hangover.
2 3 . 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 る発酵産物及び冬虫夏草抽出物の悪酔い又は二日酔い予防改善用飲食品製造のた めの使用。  23. Use of a fermented product obtained by alcoholic fermentation of citrus molasses using yeast of the genus Saccharomyces and a cordyceps extract for the manufacture of foods and drinks for preventing and improving sickness or hangover.
2 4. 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。2 4. Citrus molasses obtained by alcoholic fermentation using Saccharomyces yeast Administering an effective amount of a fermentation product.
2 5 . 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。 25. A method for promoting alcohol metabolism, which comprises administering an effective amount of a fermented product obtained by alcohol-fermenting citrus molasses using yeast of the genus Saccharomyces and a cordyceps extract.
2 6 . 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 る発酵産物の有効量を投与することを特徴とする悪酔い又は二日酔い予防改善方 法。  26. A method for preventing and improving sickness or hangover, which comprises administering an effective amount of a fermentation product obtained by alcoholic fermentation of citrus molasses using yeast of the genus Saccharomyces.
2 7 . 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悪酔い又は 二日酔い予防改善方法。  27. A method for preventing and improving sickness or hangover, which comprises administering an effective amount of a fermentation product obtained by alcoholic fermentation of citrus molasses using yeast of the genus Saccharomyces and a cordyceps extract.
PCT/JP2001/005259 2000-06-20 2001-06-20 Compositions promoting alcohol metabolism WO2002000238A1 (en)

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JP2009108099A (en) * 2009-01-13 2009-05-21 Meiji Milk Prod Co Ltd Composition for prophylaxis or amelioration of cerebrovascular disorder
EP2128239A1 (en) * 2008-05-29 2009-12-02 Young-Sam Jang Alcoholic liquor additives and method for preparing the same
JP2012105571A (en) * 2010-11-16 2012-06-07 Fuji Oil Co Ltd Fish paste and method of manufacturing the same
US10758114B2 (en) 2010-05-13 2020-09-01 Aircraft Medical Limited Laryngoscope insertion section structure

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JPS61108366A (en) * 1984-11-01 1986-05-27 Yasuji Yoshida Preparation of citrus liquor
JPH10276578A (en) * 1997-04-03 1998-10-20 Ehime Pref Gov Seika Nogyo Kyodo Kumiai Rengokai Method for effectively utilizing refuse of squeezed citrus juice

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JPS5959185A (en) * 1982-09-28 1984-04-04 Kawachichiyou Preparation of fruit spirit
JPS60126066A (en) * 1983-12-07 1985-07-05 Tadasu Sawabe Recovery of fruit juice remaining in squeezed lees of citrus fruit and device for recovering it
JPS61108366A (en) * 1984-11-01 1986-05-27 Yasuji Yoshida Preparation of citrus liquor
JPH10276578A (en) * 1997-04-03 1998-10-20 Ehime Pref Gov Seika Nogyo Kyodo Kumiai Rengokai Method for effectively utilizing refuse of squeezed citrus juice

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2128239A1 (en) * 2008-05-29 2009-12-02 Young-Sam Jang Alcoholic liquor additives and method for preparing the same
JP2009108099A (en) * 2009-01-13 2009-05-21 Meiji Milk Prod Co Ltd Composition for prophylaxis or amelioration of cerebrovascular disorder
US10758114B2 (en) 2010-05-13 2020-09-01 Aircraft Medical Limited Laryngoscope insertion section structure
US11510563B2 (en) 2010-05-13 2022-11-29 Covidien Ag Laryngoscope insertion section structure
JP2012105571A (en) * 2010-11-16 2012-06-07 Fuji Oil Co Ltd Fish paste and method of manufacturing the same

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