JP2005035997A - Alcohol metabolism improving agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an alcohol metabolism improving agent, by using a safe vegetable extract. <P>SOLUTION: This alcohol metabolism improving agent contains proanthocyanidin, because the pranthocyanidin is discovered to have excellent alcohol metabolism improving action, based on investigation of the vegetable extract which improves the alcohol metabolism. The agent especially preferably contains an extract of pine bark containing the proanthocyanidin and further, preferably, contains ascorbic acid, sesamin, and an analog thereof, so that the agent alleviates drunken sickness and a hangover. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an alcohol metabolism improver, and more particularly to an alcohol metabolism improver that is an extract of pine bark containing proanthocyanidins.

When ethanol is ingested, it is oxidized in the liver by the action of alcohol dehydrogenase (ADH) and converted to acetaldehyde. Acetaldehyde is further converted into acetic acid by the action of aldehyde dehydrogenase (ALDH) and excreted outside the body.
However, the state in which acetaldehyde, which is a metabolite of alcohol, is not fully metabolized and accumulates in the body is a state in which so-called “drunk” occurs. If aldehyde accumulates in the body, it causes skin flushing and sickness. Furthermore, it causes hangover symptoms such as headache and nausea.

  Thus, various types of plant-derived foods that are safe and have an excellent alcohol metabolism improving effect in vivo have been proposed (see, for example, Patent Documents 1 and 2).

Japanese Patent Laid-Open No. 7-285881 JP 2002-161045 A

However, although food-derived alcohol metabolism improvers that are said to have an effect of improving alcohol metabolism have been reported, few have been put into practical use, and their effects have not been sufficient.
In addition, a highly safe new plant-derived alcohol metabolism improver that can reduce hangover and hangover by improving alcohol metabolism is desired.
On the other hand, it has also become clear that plant extracts have various effects.

In view of the above circumstances, the present inventors have intensively studied a plant extract that improves alcohol metabolism, and as a result, found that proanthocyanidins, particularly pine bark extracts, have an excellent alcohol metabolism-improving action. The invention has been completed.
That is, the present invention is an alcohol metabolism improving agent characterized by containing proanthocyanidins.

  A more preferred embodiment is an alcohol metabolism improver containing ascorbic acid and its derivatives.

  More preferably, the alcohol metabolism-improving agent contains sesamin and its analog, or sesamin and its analog, and also contains ascorbic acid and its derivative.

  A more preferred embodiment is an alcohol metabolism improver, wherein the proanthocyanidins are pine bark extracts.

  Pine bark extract is a natural substance, and therefore can provide an alcohol metabolism improver that is highly safe and can reduce hangover and hangover by improving alcohol metabolism.

  The above object, other objects, features, and advantages of the present invention will become more apparent from the following description of the best mode for carrying out the invention.

  The proanthocyanidins used in the alcohol metabolism-improving agent of the present invention refers to a compound group consisting of a condensation polymer having a degree of polymerization of 2 or more having flavan-3-ol and / or flavan-3,4-diol as a structural unit. .

As the proanthocyanidins, those containing a large amount of a condensation polymer having a low degree of polymerization are preferably used.
The condensation polymer having a low polymerization degree is preferably a condensation polymer having a polymerization degree of 2 to 30 (2 to 30 mer), more preferably a condensation polymer having a polymerization degree of 2 to 10 (2 to 10 mer). A condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer) is particularly preferred. This condensation polymer having a degree of polymerization of 2 to 4 is referred to as OPC (oligomeric proanthocyanidin) in this specification.
Proanthocyanidins, a type of polyphenols, are powerful antioxidants produced by plants and are concentrated in plant leaves, bark, fruit peels or seed parts. Proanthocyanidins, especially OPCs, are specifically pine, persimmon, wild peach bark, grapes, blueberries, strawberries, avocado, black acacia, cowberry fruits or seeds, barley, wheat, soybeans, black soybeans, cacao, red beans, It is contained in tochi shells, peanut skins, and ginkgo leaves. In addition, it is known that cola nuts in West Africa, roots of Latania in Peru, and Japanese green tea contain OPC, although they are very small amounts.
OPC is a substance that cannot be generated in the human body.

  As the proanthocyanidins contained in the alcohol metabolism improver of the present invention, food materials such as the bark, fruit or seed extract described above can be used. In particular, it is preferable to use an extract of pine bark. Pine bark is rich in OPC among proanthocyanidins, and is therefore preferably used as a raw material for proanthocyanidins.

  Hereinafter, a method for preparing proanthocyanidins will be described by taking an extract of pine bark rich in OPC as an example.

Examples of the pine bark extract of the present invention include French coastal pine (Pinus Martima), larch, Japanese black pine, Japanese red pine, Japanese pine, Japanese pine, Chinese pine, Japanese pine, Ryukyu pine, Utsukushima, Japanese pine, Japanese pine, and Canadian quebec A bark extract of a plant belonging to the order of Pinus is preferably used. Among them, a bark extract of French coastal pine (Pinus Martima) is preferable.
French coastal pine is a marine pine that grows on the Atlantic coast of southern France. This French coastal pine bark contains proanthocyanidins, organic acids, and other physiologically active ingredients, and it is known that proanthocyanidins, which are the main ingredients, have a strong antioxidant action to remove active oxygen. Yes.

  The pine bark extract is obtained by extracting the pine bark with water or an organic solvent. When water is used, warm water or hot water is used. As an organic solvent used for extraction, an organic solvent that is acceptable for the production of food or drugs is used. For example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, acetone, hexane, cyclohexane , Propylene glycol, hydrous ethanol, hydrous propylene glycol, ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, and 1,1,2- Trichloroethene is mentioned. These water and organic solvent may be used alone or in combination. In particular, hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.

  A method for extracting proanthocyanidins from pine bark is not particularly limited, and for example, a warm extraction method, a supercritical fluid extraction method, or the like is used.

The supercritical fluid extraction method is a method of performing extraction using a supercritical fluid that is a fluid that exceeds the critical point (critical temperature, critical pressure) of a gas-liquid substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) or the like is used, and carbon dioxide is preferably used.
The supercritical fluid extraction method includes an extraction step of extracting a target component with a supercritical fluid and a separation step of separating the target component and the supercritical fluid. In the separation step, any one of extraction separation by pressure change, extraction separation by temperature change, or extraction separation using an adsorbent / absorbent may be performed.

  Moreover, you may perform supercritical fluid extraction by the entrainer addition method. In this method, 2 to 20 W of ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, or ketones are added to the supercritical fluid. / V% is added, and by performing supercritical fluid extraction with the obtained extraction fluid, the solubility of the target extract such as OPC and catechins (described later) in the extraction solvent is dramatically increased, or This is a method for enhancing the selectivity of separation, and a method for efficiently obtaining a pine bark extract.

Since the supercritical fluid extraction method can be operated at a relatively low temperature, it can be applied to substances that are altered or decomposed at high temperatures; the advantage that the extraction fluid does not remain; and the recycling of the solvent is possible. There is an advantage that the process can be omitted and the process becomes simple.
Extraction from pine bark may be performed by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, or the like, in addition to the above method.

  For extraction from pine bark, a plurality of extraction methods may be combined. By combining a plurality of extraction methods, it becomes possible to obtain pine bark extracts having various compositions.

  Specifically, the pine bark extract used for the alcohol metabolism improver of the present invention is prepared by the following method, but this is illustrative and is not limited to this method.

1 kg of French coastal pine bark is placed in 3 L of a saturated aqueous solution of sodium chloride and extracted at 100 ° C. for 30 minutes to obtain an extract (extraction process). Thereafter, the extract is filtered, and the resulting insoluble matter is washed with 500 mL of a saturated solution of sodium chloride to obtain a washing solution (washing step). The extract and washing solution are combined to obtain a crude extract of pine bark.
Next, 250 mL of ethyl acetate is added to the crude extract and the phases are separated to recover the ethyl acetate layer 5 times. The collected ethyl acetate solutions are combined and added directly to 200 g of anhydrous sodium sulfate for dehydration. Thereafter, the ethyl acetate solution is filtered, and the filtrate is concentrated under reduced pressure until the original volume is reduced to 1/5. The concentrated ethyl acetate solution is poured into 2 L of chloroform, and the resulting precipitate is collected by filtration. Thereafter, the precipitate is dissolved in 100 mL of ethyl acetate, and then added to 1 L of chloroform again for precipitation to perform a washing step of repeating twice. By this method, for example, about 5 g of pine bark extract containing 20% by weight or more of 2- to 4-mer OPC and containing 5% by weight or more of catechins can be obtained.

Further, in the present invention, from the viewpoint of safety when used in foods, proanthocyanidins are extracted from pine bark using ethanol or water, more preferably while heating pine bark, and an adsorbent resin ( It is preferable to use a pine bark extract in which the content of proanthocyanidins is increased using an ultrafiltration membrane such as Diaion HP-20, Sephadex-LH20, or chitin.
In addition, the upper limit of the content of proanthocyanidins in the plant extract is not particularly limited, but if the content of proanthocyanidins in the plant extract becomes high, the physiological activity of proanthocyanidins themselves may be lowered. The proanthocyanidin content in the extract is preferably less than 90% by weight, preferably less than 85% by weight, and more preferably less than 80% by weight.

  The extract derived from the raw material plant such as pine bark preferably contains OPC in terms of dry weight, preferably 20% by weight or more, more preferably 30% by weight or more. Thus, a pine bark extract is preferably used as a raw material containing OPC in a high proportion.

  In addition, in the extract extracted from the plant body using water or ethanol as described above, pentamer or more proanthocyanidins are contained, but most of them are 10 to 10 from the solubility of proanthocyanidins in polar solvents. It is 20-mer or less.

  The plant extract preferably contains 5% by weight or more of catechins together with proanthocyanidins, particularly OPC, in the raw material plant extract. Catechin is a general term for polyhydroxyflavan-3-ol. As catechins, (+)-catechin, (−)-epicatechin, (+)-gallocatechin, (−)-epigallocatechin, epigallocatechin gallate, epicatechin gallate and the like are known. In addition to (+)-catechin, which is said to be a catechin in the narrow sense, gallocatechin, afzelekin, and (+)-catechin or 3-galloyl derivatives of gallocatechin are isolated from extracts derived from raw material plants such as pine bark. Has been. Catechin has carcinogenic inhibitory effect, arteriosclerosis preventive action, fat metabolism abnormality inhibitory action, blood pressure increase inhibitory action, platelet aggregation inhibitory action, antiallergic action, antiviral action, antibacterial action, caries prevention action, bad breath prevention action, It is known to have an intestinal flora normalizing action, an active oxygen and free radical scavenging action, an antioxidant action, and the like. Catechins are known to have an anti-diabetic effect that suppresses an increase in blood sugar. Catechins have the property of activating OPC at the same time as increasing water solubility in the presence of OPC, and ingesting with OPC enhances the action of OPC.

  The catechins are preferably contained in an amount of 0.1 parts by weight or more with respect to 1 part by weight of proanthocyanidins in order to improve the solubility and function of OPC. More preferably, the raw material plant extract containing 20% by weight or more of OPC is prepared so that 5% by weight or more of catechins are contained. For example, when the catechin content of the pine bark extract is less than 5% by weight, the catechins may be added so as to be 5% by weight or more. It is most preferable to use a pine bark extract containing 5% by weight or more of catechins and 20% by weight or more of OPC.

  Proanthocyanidins, especially OPCs, are antioxidants, so they reduce the risk of adult diseases such as cancer, heart disease, and cerebral thrombosis, and improve allergic conditions such as arthritis, atopic dermatitis, and hay fever. It is known to have.

  Furthermore, in addition to antioxidant action, OPC has the effect of reducing bacterial growth in the oral cavity to reduce plaque (dental gum), the effect of restoring the elasticity of blood vessels, the effect of improving skin quality, the effect of enhancing collagen, Hyperlipidemia improving effect, preventing lipoproteins in the blood from being damaged by active oxygen, preventing damaged fat from aggregating on the inner wall of blood vessels and attaching cholesterol, active oxygen It is known to have an effect of regenerating decomposed vitamin E, an effect as an enhancer of vitamin E, and the like.

The alcohol metabolism improver of the present invention contains proanthocyanidins, preferably 0.00001% to 50% by weight, more preferably 0.001% to 40% by weight, more preferably 0, in terms of dry weight in the composition. 0.01 wt% to 20 wt%, most preferably 0.01 wt% to 5 wt%, and the daily intake per adult (body weight 60 kg) is 10 mg to 2000 mg, more preferably 20 mg to 1000 mg. Preferably it is 20 mg or more and 300 mg or less. When the daily intake per adult is 10 mg or less, there is no effect, and when it is 2000 mg or more, no further improvement in effect is observed.
In addition, the alcohol metabolism improving agent of the present invention can promote the decomposition of alcohol both before and after ingestion of alcohol, and can obtain the effect of preventing hangover and hangover. In particular, even when taken 90 minutes before ingesting alcohol, it is possible to sufficiently obtain the effect of improving the metabolism of alcohol and the effect of preventing hangover or hangover.

In addition to the above-mentioned proanthocyanidins, the alcohol metabolism improver of the present invention may contain other components usually used for quasi-drugs and the like as long as the effects of the composition are not impaired.
Examples of such components include water, other medicinal ingredients, other oils, moisturizers, surfactants, UV absorbers, absorption accelerators, fragrances, dyes, preservatives, thickeners, chelating agents, antiseptics Examples include antifungal agents. Here, examples of other medicinal ingredients include active oxygen scavengers, antioxidants, anti-inflammatory analgesics, antihistamines, antipruritics, bactericides, vitamins, hormones, and the like.

An antioxidant may be added for the purpose of increasing the stability of proanthocyanidins. Thereby, the oxidation of protein and lipid in the body can be prevented, and the effect of improving and protecting the skin quality can be obtained.
Antioxidants include carotenoids such as vitamin A, vitamin Bs, ascorbic acid, vitamin E, derivatives thereof or salts thereof, L-cysteine and derivatives or salts thereof, riboflavin, SOD, mannitol, tryptophan, Examples include extracts such as histidine, quercetin, gallic acid and its derivatives, tea extract, sesamin and its analogs, and glutathione yeast extract.

Among these, ascorbic acid and its derivatives or salts thereof not only increase the stability of proanthocyanidins and enhance their effects, but also promote the decomposition of alcohol and aldehydes in the liver.
Ascorbic acid derivatives include ascorbyl-2-phosphate, ascorbyl-2-glucoside, and salts thereof include sodium salt and potassium salt.
In the case of adding ascorbic acid, the alcohol metabolism improver of the present invention so that the weight ratio with respect to proanthocyanidins is preferably 1: 0.1 to 500, more preferably 1: 0.2 to 200. It can be contained in.

In addition, sesamin and its analogs, which are one of lignan derivatives and contained in sesame extract, also have antioxidant capacity, so not only stabilizes proanthocyanidins, but sesamin itself improves liver function. It promotes the decomposition of alcohol and aldehyde, and can obtain a synergistic effect of improving alcohol metabolism.
Examples of analogs of sesamin include sesamoline, sesaminol, sesamol, episesamin, pyrzinol, sesangoline, sympreoxide aglycone, and sesame extracts (sesame lignan, etc.) containing these.
Such sesamin and its analog are 1: 0.01-50 by weight ratio with respect to proanthocyanidins, More preferably, it is 1: 0.02-20.
In addition, you may use sesamin and its analog, ascorbic acid, its derivative (s), or its salt together. This is because these synergistic effects are expected.

A food composition containing an alcohol metabolism improver is mixed with additives such as excipients, extenders, binders, thickeners, emulsifiers, colorants, flavorings, food additives, seasonings, etc., as necessary. obtain.
For example, food additives as nutritional ingredients such as royal jelly, vitamins, protein, eggshell calcium, etc., chitosan, lecithin, chlorella powder, Ashitaba powder, Moroheiya powder; stevia powder, matcha powder, lemon powder, honey, reduced maltose, Seasonings such as lactose and molasses can be mixed.
These can be formed into capsules such as hard capsules and soft capsules, tablets or pills, or into powder, granule, tea, tea bag, bowl, liquid, paste and the like. Depending on the shape or preference, these may be eaten or consumed as they are, or may be dissolved in water, hot water or the like.

  Hereinafter, the present invention will be described more specifically with reference to examples.

(Example 1)
Eighteen 10-week-old SD male rats (Kudo Co., Ltd.) were preliminarily raised on solid feed (Oriental Yeast Co., Ltd.) for 1 week and then fasted for 12 hours.
5 ml of a 0.1% by weight aqueous solution of a pine bark extract containing 20% by weight of proanthocyanidins (containing 20% by weight of OPC, trade name: Flavangenol, Toyo Shinyaku Co., Ltd.) was administered using a sonde. 30 minutes after administration of the pine bark extract, a 15 wt% aqueous ethanol solution was forcibly administered orally so that the ethanol concentration was 1.0 g / kg. Blood was collected 0.5, 1 and 6 hours after ethanol administration, and blood ethanol and acetaldehyde were measured. The measurement was performed using a commercially available measurement kit (F-kit ethanol, F-kit acetaldehyde [Boehringer Mannheim]).
The results are shown in Table 1.

(Example 2)
In addition to the pine bark extract of Example 1, the same operation was performed except that ascorbic acid was added to the pine bark extract aqueous solution so as to be 0.1% by weight, and blood ethanol and acetaldehyde were measured.
The results are shown in Table 1.

(Comparative Example 1)
Except that the pine bark extract was not contained, the same operation as in Example 1 was performed, and blood ethanol and acetaldehyde were measured.
The results are shown in Table 1.

(Comparative Example 2)
Blood ethanol and acetaldehyde were measured in the same manner as in Example 1 except that a grape seed extract (Kikkoman Corporation) containing 38% by weight of proanthocyanidins was used instead of the pine bark extract.
The results are shown in Table 1.

From the results of Table 1, it was found that the group that took alcohol with proanthocyanidins was lower in both blood ethanol concentration and acetaldehyde concentration than the group that did not take proanthocyanidins, and was rapidly metabolized. In particular, it was found that the group that ingested the pine bark extract decreased more rapidly than the grape seed extract.
It was also found that the combination of proanthocyanidins and ascorbic acid is more effective.

(Example 3)
Five healthy adult males were subjects, and they were banned for 1 week.
And after having a subject take 3 tablets of the foodstuff 1 of Table 2 containing the pine bark extract containing 40 weight% proanthocyanidins first, the subject is equivalent to 2g per 1 kg of body weight from the test start 0 minutes. In order to become alcohol, the whiskey with 6% by weight of alcohol was consumed in 2 hours.
And I had a self-diagnosis of the state of 3 hours after the completion of alcohol intake and the physical condition of the next morning.
The weight of food is 100 mg per tablet (hereinafter the same).
The results are shown in Table 3.

(Example 4)
Except for having the same subject as above banned alcohol for one week and taking 3 tablets of pine bark extract containing 40% by weight of proanthocyanidins and food 2 shown in Table 2 containing ascorbic acid. As in the case of 3, they had alcohol ingested. And he had a self-diagnosis of physical condition 3 hours after completion of alcohol intake and the next morning.
The results are shown in Table 3.

(Example 5)
The test was conducted except that the same subject as above was banned for 1 week and took 3 tablets of food 3 shown in Table 2 containing pine bark extract and sesame extract containing 40% by weight of proanthocyanidins. Alcohol was ingested as in Example 3. And he had a self-diagnosis of physical condition 3 hours after completion of alcohol intake and the next morning.
The results are shown in Table 3.

(Comparative Example 3)
The same test subjects as described above were allowed to drink alcohol for one week, and alcohol was consumed in the same manner as in Example 3 except that 3 tablets of the food 4 shown in Table 2 were consumed. And he had a self-diagnosis of physical condition 3 hours after completion of alcohol intake and the next morning.
The results are shown in Table 3.

From the results in Table 3, it can be seen that when the pine bark extract was ingested in advance, hangover and hangover were reduced compared to the case where it was not ingested.
Moreover, when ascorbic acid, sesamin, and its analog are contained, it turns out that an effect is higher.

(Example 6)
Five healthy adult males were subjects, and they were banned for 1 week.
Then, from 0 minutes after the start of the test, the test subject ingested whiskey water with 6% by weight of alcohol in 2 hours so that the equivalent of 2 g of alcohol per 1 kg of body weight was obtained.
After the alcohol intake was completed, 3 tablets of the food 1 shown in Table 2 containing a pine bark extract containing 40% by weight of proanthocyanidins were taken.
Then I had a self-diagnosis of the physical condition of the morning the next day.
The results are shown in Table 4.

(Example 7)
The same subject as above was prohibited from drinking alcohol for one week, and was ingested in the same manner as in Example 3.
After alcohol intake was completed, 3 tablets of pine bark extract containing 40% by weight of proanthocyanidins and food 2 shown in Table 2 containing ascorbic acid were ingested.
And I had a self-diagnosis of the physical condition of the next morning.
The results are shown in Table 4.

(Example 8)
The same subject as above was prohibited from drinking alcohol for one week, and was ingested in the same manner as in Example 3.
After the alcohol intake was completed, 3 tablets of food 3 shown in Table 2 containing pine bark extract and sesame extract containing 40% by weight of proanthocyanidins were taken. And I had a self-diagnosis of the physical condition of the next morning.
The results are shown in Table 4.

(Comparative Example 4)
The same subject as above was prohibited from drinking alcohol for one week, and was ingested in the same manner as in Example 3.
After completing the intake of alcohol, 3 tablets of food 4 shown in Table 2 were taken.
And I had a self-diagnosis of the physical condition of the next morning.
The results are shown in Table 4.

From the results in Table 4, it can be seen that when the pine bark extract is ingested after ingesting alcohol, hangover and hangover can be reduced as compared to the case of not ingesting.
Moreover, when ascorbic acid, sesamin, and its analog (it exists in a sesame extract) are contained, it turns out that an effect is higher.

(Example 9: Evaluation of alcohol metabolism by breath alcohol)
Tablets containing 30 mg of shochu with 25 degree alcohol and pine bark extract per tablet (one tablet is a 250 mg tablet, 30 mg of pine bark extract (same as in Example 1) and crystalline cellulose, Using sugar ester, reduced maltose and trehalose), the influence on alcohol metabolism was evaluated as follows.
First, the breath alcohol concentration before alcohol intake from five subjects was measured with an alcohol detector (manufactured by Chuo Motor Co., Ltd.). After confirming that the measurement result showed 0, all of the 60 mL of shochu was consumed within 5 minutes. Next, 30, 60, 120, and 150 minutes after the start of ingestion of shochu, the breath alcohol concentration was measured five times, and the average value was calculated.
Next, the same test was conducted at the same time on the next day, except that four tablets containing the pine bark extract were ingested 90 minutes before ingesting shochu. The alcohol concentration was measured.
On the 3rd day, 60 minutes before ingesting the shochu, and on the 4th day, take 4 tablets containing the pine bark extract 30 minutes before. Were measured and the average value was determined.
The results are shown in Table 5.

  From the results of Table 5, it can be seen that the pine bark extract containing the proanthocyanidins of the present invention decreases in an earlier time compared to the case where the alcohol concentration in the breath after ingestion was not ingested. That is, it can be seen that by taking the pine bark extract containing the proanthocyanidins of the present invention before ingesting alcohol, it is possible to promote alcohol metabolism and prevent hangover and hangover.

  The alcohol metabolism improver according to the present invention can be used in the food processing industry and the like.

Claims (4)

  An alcohol metabolism improver comprising proanthocyanidins.   2. The alcohol metabolism-improving agent according to claim 1, comprising ascorbic acid and a derivative thereof.   The alcohol metabolism-improving agent according to claim 1 or 2, comprising sesamin and an analog thereof.   4. The alcohol metabolism improver according to claim 1, wherein the proanthocyanidins are extracted from pine bark.