WO2014077135A1 - Agent réduisant le taux d'acétaldéhyde dans le sang - Google Patents

Agent réduisant le taux d'acétaldéhyde dans le sang Download PDF

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Publication number
WO2014077135A1
WO2014077135A1 PCT/JP2013/079576 JP2013079576W WO2014077135A1 WO 2014077135 A1 WO2014077135 A1 WO 2014077135A1 JP 2013079576 W JP2013079576 W JP 2013079576W WO 2014077135 A1 WO2014077135 A1 WO 2014077135A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
blood acetaldehyde
citric
ascorbic
reducing agent
Prior art date
Application number
PCT/JP2013/079576
Other languages
English (en)
Japanese (ja)
Inventor
大嶋　俊二
明弘 根本
比呂子 石切山
Original Assignee
アサヒグループホールディングス株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by アサヒグループホールディングス株式会社 filed Critical アサヒグループホールディングス株式会社
Priority to JP2014546935A priority Critical patent/JP6220792B2/ja
Publication of WO2014077135A1 publication Critical patent/WO2014077135A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • 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
    • 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
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a blood acetaldehyde reducing agent, and more particularly to a blood acetaldehyde reducing agent that efficiently lowers the blood acetaldehyde concentration after alcohol intake by drinking.
  • Alcohol taken into the body by drinking is metabolized by alcohol dehydrogenase in the liver cells and decomposed into acetaldehyde having strong hepatotoxicity, and then acetaldehyde is rapidly decomposed into acetic acid.
  • Acetic acid is released from the liver into the blood, enters the TCA circuit as a source of energy for peripheral tissues, and is eventually broken down into carbon dioxide and water.
  • acetaldehyde is not decomposed into acetic acid and causes discomfort such as nausea and headache.
  • Patent Document 1 discloses that a higher aliphatic alcohol having 22 to 36 carbon atoms is an active ingredient, and Patent Document 2 contains kale and / or kale extract as an active ingredient.
  • Patent Document 3 discloses a blood acetaldehyde reducing agent mainly composed of a herbal extract and supplemented with citric acid or vitamin C.
  • the present invention solves the above-mentioned conventional problems, and an object of the present invention is to provide a blood acetaldehyde reducing agent excellent in effect and safety by using raw materials that are easily available.
  • the present invention provides use of at least one selected from the group consisting of ascorbic acids [A] and acetic acid [C] and citric acids [B] in a blood acetaldehyde reducing agent.
  • the present invention also provides use of ascorbic acids [A] and citric acids [B] in a blood acetaldehyde reducing agent.
  • weight ratio [A / B] of ascorbic acids [A] and citric acids [B] is more than 0.33 and less than 1.33.
  • the weight ratio [A / B] of ascorbic acids [A] and citric acids [B] is 0.5 to 1.
  • the dosage of ascorbic acids [A] and citric acids [B] is 0.05 g / kg or more based on body weight.
  • acetic acid [C] is further used in the above use.
  • the present invention also provides use of acetic acid [C] and citric acids [B] in a blood acetaldehyde reducing agent.
  • the weight ratio [C / B] of acetic acid [C] and citric acids [B] is 0.01 to 5.
  • the dosage of ascorbic acids [A] and citric acids [B] is 0.01 g / kg or more based on body weight, and the dosage of acetic acid [C] is 0.1 g / kg or less. is there.
  • the ascorbic acid is at least one selected from the group consisting of ascorbic acid, sodium ascorbate, calcium ascorbate and potassium ascorbate.
  • the citric acid is at least one selected from the group consisting of citric acid, sodium citrate and potassium citrate.
  • the present invention also provides a blood acetaldehyde reducing agent comprising at least one selected from the group consisting of ascorbic acids [A] and acetic acid [C] and citric acids [B].
  • ascorbic acid refers to ascorbic acid and ascorbate that can be added to food.
  • specific examples of ascorbic acids include ascorbic acid, sodium ascorbate, calcium ascorbate and potassium ascorbate.
  • citric acids refer to citric acid and citrate that can be added to food.
  • Specific examples of citric acids include citric acid, sodium citrate and potassium citrate.
  • examples of such foods include citrus fruits such as lemons and tangerines, and fruits such as peaches, plums, strawberries, and kiwifruits. These may be pulverized, squeezed or the like to use a portion containing citric acids.
  • the amount of ascorbic acid and citric acid used is adjusted so that the weight ratio between them is 0.3 / 1 to 1.4 / 1. If the weight ratio of ascorbic acid and citric acid is less than 0.3 / 1 or exceeds 1.4 / 1, the effect of lowering the blood acetaldehyde concentration becomes insufficient. That is, when the weight ratio of ascorbic acid and citric acid is 0.3 / 1 to 1.4 / 1, a synergistic effect of using both is recognized. In addition, when there are more ascorbic acids than citrates, there exists a tendency for an effect to be attenuated.
  • the weight ratio of ascorbic acid and citric acid is preferably more than 0.33 and less than 1.33, more preferably 0.4 to 1.25, still more preferably 0.45 to 1.1, and most preferably 0.8. 5 to 1.0.
  • Ascorbic acid and citric acid can be used in combination as a blood acetaldehyde reducing agent. Accordingly, when ascorbic acid and citric acid are ingested by humans as a blood acetaldehyde reducing agent, the dosage may be determined appropriately depending on the effect.
  • the dose of citric acid is about 0.05 g / kg or more based on body weight.
  • the dose of citric acid is less than 0.05 g / kg based on body weight, the effect of lowering the blood acetaldehyde concentration is reduced.
  • a preferred dosage is about 0.1 g / kg or more, more preferably about 0.2 g / kg or more.
  • the dose of ascorbic acid can be adjusted in consideration of the weight ratio with citric acid.
  • Acetic acid is a component contained in approximately 3% of vinegar, and if it is in an appropriate amount, it is harmless to the human body. Acetic acid has an effect of reducing blood acetaldehyde.
  • the blood acetaldehyde-reducing action of acetic acid is synergistically enhanced particularly when acetic acid and citric acid are used in combination.
  • the blood acetaldehyde reducing action is further enhanced.
  • the amount of acetic acid used is 0.01 to 5, preferably 0.05 to 2, and more preferably 0.1 to 1 by weight ratio with respect to citric acid. If the amount of acetic acid used is less than 0.01 or exceeds 5, it is difficult to obtain a synergistic effect of reducing blood acetaldehyde.
  • Acetic acid has a strong acidity and may adversely affect the digestive tract, so it is not preferable to take it in excess of the appropriate amount.
  • the dosage of acetic acid is 0.1 g / kg or less, preferably 0.05 g / kg or less, more preferably 0.02 g / kg or less.
  • the dosage of citric acid may be 0.01 g / kg or more, preferably 0.03 g / kg or more based on body weight.
  • the dose of ascorbic acid can be adjusted taking into account the weight ratio with citric acid.
  • the effect of efficiently suppressing the blood acetaldehyde concentration after alcohol consumption by drinking is strong when taken at the time of drinking or by taking the composition of the present invention before drinking.
  • the blood acetaldehyde reducing agent of the present invention may be prepared in the form of pharmaceuticals, foods or beverages.
  • a form called a supplement is preferable, and a form such as a tablet or granule is preferable.
  • As a beverage it is common to adjust to a form such as a drink. You may mix with alcoholic beverages.
  • These foods or beverages may be produced by a conventional method. For example, it can be produced by the following method.
  • granules In the case of granules, it can be produced with a fluid granulator or a tumbling granulator together with additives such as excipients and sweeteners to ascorbic acids and citric acids.
  • additives such as excipients, sweeteners, lubricants are added and mixed, and then compressed into tablets using a rotary tableting machine, single-punch tableting machine, etc. Can be manufactured.
  • excipients include starch (corn starch, potato starch, wheat starch, rice starch, etc.), lactose colloidal silica, crystalline cellulose, anhydrous silicic acid, anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, light anhydrous silicic acid. Hydrous silicon dioxide, silicon dioxide, aluminum oxide, magnesium carbonate, precipitated calcium carbonate, crystalline cellulose, synthetic aluminum silicate, magnesium silicate, magnesium metasilicate aluminate, dextrin, carmellose calcium and the like. These carriers may be used alone or in combination of two or more.
  • the crystalline cellulose includes microcrystalline cellulose.
  • sweetener examples include sugar, sugar alcohol, glucose, fructose, galactose, mannose, lactose, maltose, sucrose, sucrose (including purified sucrose), trehalose, mannitol, sorbitol, maltitol, aspartame, erythritol. Xylitol and the like, and these may be used alone or in combination of two or more.
  • the lubricant examples include magnesium stearate, calcium stearate, sodium stearyl fumarate, stearic acid, talc, sucrose fatty acid ester, glycerin fatty acid ester, polyethylene glycol, vegetable oil and the like.
  • the lubricant may be added by any of the method of adding to the granule before tableting and mixing, or the method of adhering directly to the punch or die during tableting.
  • Water may be water that is suitable for drinking, and is, for example, pure water, hard water, soft water, or ion-exchanged water, and deionized ion-exchanged water is preferable in order to suppress ascorbic acid deterioration.
  • test solution prepared by dissolving either active substance ascorbic acid or citric acid in 5% (v / v) ethanol-containing water is prepared in male BALB / c mice 7 weeks of age or older, based on body weight. It was administered by gavage in an amount of 8.45 ml / kg. The concentration of each test solution was adjusted so that the dose of ascorbic acid or citric acid became the values shown in Tables 1 and 2. For example, when the dose was 0.5 g / kg, the ascorbic acid concentration or citric acid concentration of the test solution was 5.9% by weight. A group to which only 5% (v / v) ethanol-containing water was administered was used as a control.
  • the blood acetaldehyde concentration inhibition rate was determined by comparing the blood acetaldehyde concentration of the above control with the blood acetaldehyde concentration of the administration group, and calculating the decreased blood acetaldehyde concentration ratio. For example, when the dose was 0.5 g / kg, ascorbic acid had a blood acetaldehyde concentration inhibition rate of 39.0%, and citric acid had a blood acetaldehyde concentration inhibition rate of 38.6%.
  • the blood acetaldehyde concentration inhibition rate values of ascorbic acid and citric acid are used as basic data for calculating theoretical values when both are used in combination.
  • the dose of citric acid was fixed at 0.3 g / kg, and the dose of ascorbic acid was changed stepwise.
  • the combination ratio of ascorbic acid and citric acid was 0.5 or more, the effect of exceeding the theoretical value was demonstrated with respect to citric acid 1, and the synergistic effect was strongest when 1/1.
  • the combination ratio of ascorbic acid and citric acid was fixed at 1, and the doses of both compounds were changed.
  • the doses of ascorbic acid and citric acid were 0.05 g / kg or more, superiority to the theoretical value was recognized.
  • the blood acetaldehyde concentration inhibition rate was determined by comparing the blood acetaldehyde concentration of the above control with the blood acetaldehyde concentration of the administration group, and calculating the decreased blood acetaldehyde concentration ratio.
  • Example 14 The concentration of blood acetaldehyde in each test solution was the same as in the reference example except that the test solution was adjusted so that the doses of active ingredients ascorbic acid, citric acid and acetic acid were as shown in Table 6. The inhibition rate was measured. Further, the theoretical value of the blood acetaldehyde concentration inhibition rate was calculated in the same manner as described above.
  • the blood acetaldehyde concentration after alcohol intake by drinking can be reduced efficiently, it is extremely useful as a food or beverage that effectively prevents hangovers such as nausea and headache after drinking a large amount of alcohol due to excessive drinking.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Engineering & Computer Science (AREA)
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Abstract

Le problème décrit par la présente invention est de fournir un agent réduisant le taux d'acétaldéhyde dans le sang présentant un excellent effet et une excellente sûreté à l'aide d'une matière première facilement disponible. Pour ce faire, la présente invention propose l'utilisation d'au moins un constituant choisi dans le groupe constitué par un composé acide ascorbique [A] et de l'acide acétique [C] et un composé acide citrique [B] dans l'agent réduisant le taux d'acétaldéhyde dans le sang.
PCT/JP2013/079576 2012-11-15 2013-10-31 Agent réduisant le taux d'acétaldéhyde dans le sang WO2014077135A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2014546935A JP6220792B2 (ja) 2012-11-15 2013-10-31 血中アセトアルデヒド低減剤

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JP2012-251408 2012-11-15
JP2012251408 2012-11-15

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WO2014077135A1 true WO2014077135A1 (fr) 2014-05-22

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021157627A1 (fr) * 2020-02-04 2021-08-12 株式会社東洋新薬 Composition orale
US20210353575A1 (en) * 2018-10-16 2021-11-18 Nippon Chemiphar Co., Ltd. Agent for suppressing alcohol sickness or hangover due to alcoholic beverage ingestion

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62143678A (ja) * 1985-12-17 1987-06-26 Nakano Vinegar Co Ltd 深酔い防止アルコ−ル飲料の製造法
JPS63169974A (ja) * 1985-06-24 1988-07-13 マンフレ−ト・バンネス フルクト−ス・ビタミンｃ、キニン及び／又はこれらの代替物を含有する飲料
WO2006064550A1 (fr) * 2004-12-14 2006-06-22 Toyo Shinyaku Co.,Ltd. Agent facilitant le métabolisme de l'alcool et boisson alcoolique

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63169974A (ja) * 1985-06-24 1988-07-13 マンフレ−ト・バンネス フルクト−ス・ビタミンｃ、キニン及び／又はこれらの代替物を含有する飲料
JPS62143678A (ja) * 1985-12-17 1987-06-26 Nakano Vinegar Co Ltd 深酔い防止アルコ−ル飲料の製造法
WO2006064550A1 (fr) * 2004-12-14 2006-06-22 Toyo Shinyaku Co.,Ltd. Agent facilitant le métabolisme de l'alcool et boisson alcoolique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J.P. BONJOUR: "VITAMINS AND ALCOHOLISM", INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH, vol. 49, no. 4, 1 January 1979 (1979-01-01), pages 434 - 441 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210353575A1 (en) * 2018-10-16 2021-11-18 Nippon Chemiphar Co., Ltd. Agent for suppressing alcohol sickness or hangover due to alcoholic beverage ingestion
WO2021157627A1 (fr) * 2020-02-04 2021-08-12 株式会社東洋新薬 Composition orale

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JP6220792B2 (ja) 2017-10-25
JPWO2014077135A1 (ja) 2017-01-05

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