JPH08169831A - Agent for promoting metabolism of alcohol in body and its production - Google Patents

Abstract

PURPOSE: To obtain an agent for promoting the metabolism of alcohol in the body, containing caffeine as an active component and effective for suppressing and preventing the symptoms such as nausea, retching, vomition, hangover, vertigo, foul breath, etc., caused by the excessive drinking. CONSTITUTION: Caffeine extracted from tea is used as an active component and included in the promoting agent at a rate of 0.5-500mg, preferably 0.5-50mg based on 1kg body-weight of the person to be treated. Caffeine promotes the metabolism of ethanol and acetaldehyde in the body and, accordingly, the metabolism of carbonyl compound and carboxylic acid produced as metabolic products. The above action of caffeine and the action of catechin to promote the metabolism of the metabolic product of the alcohol in the body are synergistically developed by the addition of catechin extracted from tea to caffeine to rapidly eliminate the toxin caused by the alcohol in the body and, accordingly, the uncomfortable symptoms caused by excessive drinking can be suppressed in a short time. An internal agent for oral administration is prepared by adding a sweetener, a flavor, etc., and used in the form of syrup, tablet, capsule, powder, etc.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a body alcohol which exerts an excellent effect in suppressing or preventing unpleasant symptoms such as nausea and other discomforts caused by excessive drinking, nausea, vomiting, hangover, dizziness or bad breath. The present invention relates to a metabolism promoter and a method for producing the same.

[0002]

2. Description of the Related Art Unpleasant symptoms such as nausea and other discomforts, nausea, vomiting, hangover, dizziness or bad breath, which are harmful effects of excessive drinking, are caused by
It has been considered that the effects of alcohols such as ethanol remaining in the body and acetaldehyde which is a metabolite thereof (hereinafter, these are referred to as body alcohols) are related by the conventional research, and prevent or suppress such symptoms. Therefore, researches on pharmaceuticals and the like that promote the metabolism of alcohol in the body to lower the concentration of alcohol in the body have been advanced.
Among them, the components derived from natural plants have been particularly noted in terms of safety and the like.

However, natural tea (Camellia
Regarding the component derived from sinennsis), JP-A-4-145028 has only disclosed an alcohol absorption inhibitor having saponin as an active ingredient, which is contained in tea seeds in a large amount. Moreover, this invention does not disclose anything about the metabolism of alcohol in the body. Therefore, the inventors of the present invention have disclosed in Japanese Patent Laid-Open No. 6-
In 263648, it was disclosed that catechin extracted from tea has an action of promoting alcohol metabolism in the body.

As a result of further intensive research on the components derived from tea, the present inventors succeeded in finding an excellent in vivo alcohol metabolism promoting action on caffeine newly extracted from tea, and In addition, we succeeded in finding a metabolism-promoting action of acetic acid and acetone, which are metabolism products of ethanol and acetaldehyde, in catechin, and completed the present invention by these successes. Another object of the present invention is to provide an agent for promoting alcohol metabolism in the body, which exerts an action of promoting a decrease in the concentration of alcohol in the body, can be safely used, and can be manufactured at low cost.

With respect to conventional caffeine, an invention in which caffeine is added to a drug or a quasi drug in consideration of its excitement-inducing action (JP-A-4-32802, JP-A-6-62).
263648) and its peripheral nerve stimulating action, and invention added to a drug or quasi drug (JP-A-4-273).
814) and the like were disclosed, but an invention relating to the action of caffeine itself to promote alcohol in the body was not disclosed.

[0006]

To achieve the above object, the present invention proposes an agent for promoting alcohol metabolism in the body containing caffeine as an active ingredient. In the present invention, caffeine refers to caffeine or a mixture of caffeine and a caffeine derivative, that is, theophylline or theobromine. According to this in-vivo alcohol metabolism promoter, the alcohol concentration in the body can be reduced in a short time due to the excellent alcohol metabolism promoting action of caffeine.

Here, the caffeine content is preferably adjusted so as to be in the range of about 0.5 mg to about 500 mg per 1 kg of body weight of the ingested person. Especially about 0.5
It is preferably contained in the range of mg to about 50 mg. About 0.5 per kg body weight for people who consume caffeine
It is clear from the animal administration test described below that an alcohol metabolism promoting effect can be obtained by ingesting more than mg. On the other hand, according to the Japanese Pharmacopoeia, the dose of caffeine is preferably about 500 mg or less per 1 kg of body weight, especially about 10% of the gastrointestinal disorder caused by excessive drinking, that is, about 50 mg or less. desirable.

The present invention also proposes a body alcohol metabolism promoter containing caffeine and catechin. According to this body alcohol metabolism promoter, the body alcohol metabolism action of caffeine and the metabolism-promoting action of catechin of the body alcohol metabolite of catechin act synergistically to reduce the concentration of toxin caused by body alcohol. Can be lowered in time. In the present invention, catechin means epicatechin (EC), epicatechin gallate (ECG)
, Epigallocatechin (EGC) and epigallocatechin gallate (EGCg), or a mixture of two or more selected from these.

Here, the content of caffeine and catechin is in the range of about 0.5 mg to about 500 mg per kg of body weight for a person who ingests caffeine, and catechin is also about 2. mg per kg of body weight. It is preferable to adjust the content to be 5 mg or more. Although the caffeine content is as described above, regarding the catechin content, if about 2.5 mg of catechin per 1 kg of body weight is ingested, a sufficient metabolism promoting effect can be obtained. It is also clear from.

As a preferred example of the alcohol metabolism promoter in the present invention, tea is extracted with hot water or an organic solvent or a mixed solution of hot water and an organic solvent, and polysaccharides, proteins and inorganic salts are removed from the extract. A tea extract obtained by containing caffeine in an amount of about 0.5 mg to about 500 mg per kg body weight of a person who ingests caffeine, and also containing catechin in an amount of about 2.5 mg or more per kg body weight. Some include tea extract as an active ingredient. This body alcohol metabolism promoter contains, in addition to the above-mentioned caffeine and catechin, amino acids such as asparagine, serine, alanine, arginine, aspartic acid and glutamic acid, which are known to have a body alcohol metabolism promoting action, and are excellent in the body. The alcohol metabolism effect can be obtained. In addition,
The above-mentioned tea (Camellia sinennsis) is a generic name for raw materials such as green tea, oolong tea and black tea.

The present invention also proposes a method for producing a body alcohol metabolism promoter. That is, tea is extracted with hot water or an organic solvent or a mixed solution of hot water and an organic solvent, and polysaccharides, proteins and inorganic salts are removed from the obtained extract to obtain a tea extract. Is the way. When produced in this manner, the above-mentioned preferred examples of the alcohol metabolism promoter in the body can be obtained.

As the form of the alcohol metabolism promoter in the present invention, caffeine, a mixture of caffeine and catechin, or a tea extract obtained by the above-mentioned production method,
Fructose having an alcohol metabolism promoting action, SH amino acids such as L-cysteine, etc., preferably sweeteners, flavors, etc., respectively, are added, and liquids, tablets, capsules, powders for easy oral ingestion. And the like. For example, in the case of producing 30 ml of liquid preparation, the concentration of caffeine is adjusted to about 0.0 so that the contents of caffeine and catechin are within the above range.
The concentration may be adjusted to 016% (g / ml) to about 1.6% (g / ml) and the catechin concentration to about 0.0083% (g / ml) or more.

The above tea extract is preferably adjusted to a drinking concentration of about 0.1 to about 5% by weight, and a sweetening agent, a flavoring agent, a preservative and the like are added to the tea extract to give a round or ring-like shape. Alternatively, it may be molded into a tablet or capsule shape such as a plate shape, or may be made into a powder or liquid state and packed in a brown bottle container or the like to be used as a mouth refreshing agent.

[0014]

【Example】

(Example 1: Method for producing tea extract) Fresh leaves of Thea sinensis L. were subjected to rough tea processing according to a standard method, and 10 kg of these dried leaves
After adding 100 liters of purified water and extracting at 90 ° C for 10 minutes, the extract is filtered (centrifugation), and the obtained extract is concentrated and dried to obtain a dry powdery crude tea extract. Obtained. Furthermore, this crude tea extract was passed through a HP-20 synthetic adsorption resin, and the non-adsorbed fraction was eluted with 6 times the amount of ion-exchanged water of the adsorption resin to remove the polysaccharides, proteins and inorganic salts. The adsorption fraction was eluted with 5 volumes of ethanol, and the obtained adsorption fraction was concentrated and freeze-dried to obtain a dry powdery tea extract.

When the composition of this tea extract was analyzed,
Epigallocatechin 16.61%, epigallocatechin gallate 13.72%, epicatechin 3.40%, epicatechin gallate 2.19%, caffeine 9.93%, aspartic acid 0.26%, glutamic acid 0.30 %, Aspartic acid 0.05%, serine 0.08%, glutamine 0.11%, arginine 0.11%, alanine 0.0
4, methionine 0.04%, theanine 0.97%, and gamma-aminobutyric acid 0.05%. All the above percentages are weight percentages.

Example 2 Administration Test 1 Male ICR mice were divided into two groups, one group containing caffeine dissolved in physiological saline at 50 mg / k body weight.
Orally administered (hereinafter, this mouse is referred to as 50 mg-administered mouse), and 1 hour after that, 2 g per 1 kg of body weight (20
Ethanol (% W / V) was orally administered using a catheter. In addition, only saline was orally administered to the other group, and 1 hour after that, 2 g (20% W / V) of ethanol per kg of body weight was orally administered using a catheter.
It was used as a control for 0 mg-administered mice. Blood and liver of each mouse were collected before and 1 and 3 hours after ethanol administration, and the concentrations of ethanol, acetaldehyde, acetate and acetone in blood and liver were measured.

Similarly, using an ICR male mouse,
These were divided into two groups, and caffeine weighed 1 kg for each group.
Oral administration of 300 mg / kg per mouse (hereinafter, this mouse is referred to as 300 mg-administered mouse), and 1 hour after that, 2 g (20% W / V) of ethanol per kg of body weight is orally administered using a catheter, while the other groups are treated as above. Similarly,
The control was performed on 300 mg-administered mice, and blood and liver were collected from each mouse before and 1 and 3 hours after ethanol administration, and the ethanol concentrations in blood and liver were measured.

The measuring method at this time is as follows. 0.5 ml of blood and 0.5 g of liver were freeze-dried using liquid nitrogen to make powder, and this powder was immediately cooled. PCA reagent (0.6N perchloric acid, 30 mM thiour
ea, 0.1mM EDTA in saline) 2.5ml 4
Centrifuge for 10 minutes at 3000 rpm at 3000C. And
The obtained supernatant sample was divided into two, while (I) was added with ethanol,
Put 1 ml into a vial for measuring acetaldehyde and acetone, and use 0.003% t-but as an internal standard substance.
After adding 0.1 ml of anol, heat at 65 ° C for 15 minutes,
This was injected into GC for quantitative analysis. On the other hand, the other (II) was also put in a bottle for measuring acetaldehyde, 100 μl of methanol and 50 μl of sulfuric acid were added to methylate acetate, and 0.02% n-bu was added as an internal standard substance.
After adding 0.1 ml of tanol, the mixture was heated at 55 ° C. for 30 minutes and injected into the same GC for quantitative analysis.

FIGS. 1, 2, 3, and 4 show the concentrations of ethanol, acetaldehyde, acetate, and acetone in blood in 50 mg-administered mice and control mice, and FIGS. 5, 6, 7 and 8 show Similarly, it shows the concentrations of ethanol, acetaldehyde, acetate and acetone in the liver. Further, FIG. 9 shows the ethanol concentration in blood of the 300 mg-administered mouse and the control mouse, and FIG. 10 shows the ethanol concentration in the liver of the 300 mg-administered mouse and the control mouse.

As a result, the concentration of acetaldehyde in blood of 50 mg-administered mice tended to be lower than that of control mice, and it was almost eliminated from the blood 3 hours after ethanol administration. The effect of promoting alcohol metabolism can be confirmed. Further, since the concentrations of acetate and acetone containing the metabolites of ethanol and acetaldehyde tend to be higher than those of control mice, the effect of promoting caffeine on alcohol metabolism can be confirmed. The results in the liver were similar to those in the blood. Furthermore, 300m
The difference between the g-administered mouse and the control mouse shows a more remarkable tendency than the 50-mg-administered mouse.

Here, the effective amount of caffeine in the agent for promoting alcohol metabolism in the body of the present invention is generally the effective amount of caffeine in humans, which is 100 minutes of the effective amount of animal test results from the precedents of clinical trials of pharmaceuticals. Since it has been found that it is desirable to set the amount to about 1 of the above, it is sufficient to contain about 0.5 mg per 1 kg of body weight for the ingested person. In addition, the upper limit is a body weight of 1k based on the Japanese Pharmacopoeia.
It is desirable that the extreme amount is 500 mg per g, especially about 10% of the gastrointestinal tract which is rough due to excessive drinking, that is, about 50 mg or less.

(Example 3: Administration test 2) Male ICR mice were divided into two groups. One group was prepared by dissolving the tea extract obtained in Example 1 above in physiological saline.
500 mg per kg was orally administered (hereinafter, this mouse is referred to as tea extract-administered mouse), and 1 hour later, the mouse was orally administered with 2 g / kg body weight (20% W / V) of ethanol using a catheter. In this case, the caffeine concentration in the tea extract obtained in Example 1 was 9.93%, and thus the tea extract 5
This means that 49.5 mg of caffeine is contained in 00 mg. Oral saline was orally administered to the other groups, and 1 hour after that, the mice were weighed 2 g / kg of body weight.
(20% W / V) ethanol was orally administered using a catheter, and this mouse was used as a control for the tea extract-administered mouse. For each mouse, blood was collected before ethanol administration and 1 hour and 3 hours after ethanol administration, and the content of ethanol and acetaldehyde in the blood was measured. The measurement of ethanol and acetaldehyde was performed in the same manner as in the above administration test 1.

FIGS. 11 and 12 show the ethanol concentration and acetaldehyde concentration in blood of the tea extract-administered mouse and the control mouse, respectively.

As a result, both the ethanol concentration and the acetaldehyde concentration of the tea extract-administered mouse showed a large decrease in the concentration as compared with that of the control mouse, and the alcohol metabolism promoting effect of the tea extract can be confirmed. Also,
The dose of caffeine in the tea extract-administered mouse corresponds to the administration of 50 mg of caffeine in the above administration test 1,
Comparing the results of FIG. 1 and FIG. 2 with the results of FIG. 11 and FIG. 12, the concentration decrease rate of the tea extract mouse was higher than that of the 50 mg-administered mouse for both the ethanol and acetaldehyde concentrations. From this, it can be confirmed that the tea extract mouse has a more prominent alcohol metabolism promoting action. This is the tea extract
It contains amino acids known to promote alcohol metabolism, such as asparagine, serine, alanine, arginine, aspartic acid and glutamic acid, and it is the result of the synergistic action of caffeine and these substances. Presumed.

Example 4 Administration Test 3 Next, the metabolism promoting action of catechin was examined. ICR male mice were divided into 4 groups, and each group contained 75 m of mouse per 1 kg of body weight.
g of epigallocatechin gallate (hereinafter referred to as EGCg) was orally administered to another group, and mice were given 2 g / kg of body weight.
Oral administration of 25 mg of EGCg, and another group was given to mice in which 170 mg of epigallocatechin (kg / body weight)
1 hour after the oral administration of EGC, 2 g / kg of body weight (20
Ethanol (% W / V) was orally administered using a catheter. In the remaining group, 2 g / kg body weight (20% W / V) was administered 1 hour after oral administration of physiological saline only.
Was orally administered using a catheter and this mouse was used as a control. For each mouse, 1 from ethanol administration and 1 from ethanol administration, respectively.
Blood was collected after 3 hours and after 3 hours, and the contents of ethanol, acetaldehyde, acetate, and acetone in the blood were measured. In addition, the measurement of ethanol, acetaldehyde, acetate, and acetone was conducted according to the above-mentioned administration test 1
I went the same way.

FIG. 13, FIG. 14, FIG. 15 and FIG. 16 respectively show the ethanol, acetaldehyde, acetate and acetone concentrations of these catechins administered and the control.

As a result, when any catechin was administered, there was no difference in the ethanol concentration from the control value, and also in the acetaldehyde concentration.
No noticeable difference was observed except when EGCg of 225 mg / kg was administered. However, in the case of the acetate concentration and the acetone concentration, both administrations of catechins show a remarkable reduction rate in concentration as compared with the control value. From this, it can be confirmed that catechin has an action of promoting metabolism of acetate and acetone which are metabolites such as ethanol and acetaldehyde.

Therefore, if caffeine plus catechin is administered, the body alcohol metabolism of caffeine and the specific metabolism of catechin such as acetate and acetone act synergistically, and Therefore, the toxin caused by alcohol can be eliminated in a shorter time.

Here, it has been found that the effective amount of the substance that is usually drunk for humans is generally about 1/30 of the effective amount for animals. From administration test 3, at least 75 mg / k
Since the concentration of acetate and acetone was sufficiently reduced by administering 1 g of EGCg, the effective concentration of catechin for humans should be about 2.5 mg or more in terms of EGCg per kg body weight of the ingested person. Is enough.

Example 5 A drink formulation having the following formulation was prepared so as to contain 50 mg of caffeine. Caffeine 50 mg Theanine 1000 mg Taurine 1000 mg Royal Jelly 200 mg Inositol 50 mg Nicotinic Acid Amide 20 mg Vitamin B1 Sulfate 5 mg Vitamin B2 Phosphate 5 mg Vitamin B6 5 mg Purified Water Appropriate amount

Example 6 A drink formulation having the following formulation containing 50 mg of caffeine was produced based on the tea extract. Total amount in 100 ml Caffeine 50 mg Theanine 1000 mg Taurine 1000 mg Royal jelly 200 mg Inositol 50 mg Nicotinic acid amide 20 mg Vitamin B1 sulfate 5 mg Vitamin B2 phosphate 5 mg Vitamin B6 5 mg Catechin 200 mg Aspartic acid 260 mg Glutamine 90 mg asparagine 110 mg Aspartate 300 mg Aspartate 300 mg Methionine 40mg Gamma-aminobutyric acid (GABA) 50mg Purified water Suitable amount

(Example 7) Based on the tea extract, a granulating agent and a flavoring agent were added thereto, and the mixture was molded into tablets, capsules and powders, and a mouthwash of the following formulation containing 5 mg of caffeine was prepared. Was manufactured. Caffeine 50 mg Theanine 500 mg Taurine 500 mg Royal Jelly 20 mg Inositol 50 mg Nicotinic Acid Amide 20 mg Vitamin B1 Sulfate 5 mg Vitamin B2 Phosphate 5 mg Vitamin B6 5 mg Catechin 200 mg Aspartic Acid 26 mg Glutamine Nacetamine 8 mg 30 mg Methionine 4mg Gamma-aminobutyric acid (GABA) 5mg Granulating agent Suitable amount

(Example 8) Based on the tea extract, a granulating agent and a flavoring agent were added thereto, and the mixture was molded into tablets, capsules and powders, and a mouthwash of the following formulation containing 5 mg of caffeine was prepared. Was manufactured. Caffeine 50 mg Theanine 500 mg Taurine 500 mg Royal Jelly 20 mg Inositol 50 mg Nicotinic Acid Amide 20 mg Vitamin B1 Sulfate 5 mg Vitamin B2 Phosphate 5 mg Vitamin B6 5 mg L-Cysteine 50 mg Catechin 200 mg Aspartic Acid 26 mg 5 Aspartic Acid 26 mg 8 Glutamin 28 mg Glutamin 30 mg Arginine 11 mg Alanine 4 mg Methionine 4 mg Gamma-aminobutyric acid (GABA) 5 mg Fructose 100 mg Granulating agent

[0034]

The agent for promoting alcohol metabolism in the body of the present invention comprises:
To increase the concentration of ethanol and acetaldehyde in blood and liver by the action of caffeine by ingesting before drinking, when drinking too much, or when feeling unpleasant symptoms after drinking too much. Therefore, various unpleasant symptoms due to excessive drinking can be prevented or eliminated.

Further, when the in-vivo alcohol metabolism promoting agent of the present invention containing caffeine and catechin is ingested, the action of caffeine promotes the metabolism of ethanol and acetaldehyde in the body, and further its metabolites. Since it can promote the metabolism of a carbonyl compound or carboxylic acid, the metabolic promoting effects of caffeine and catechin work synergistically to eliminate various unpleasant symptoms caused by excessive drinking in a shorter time. You can

Since both caffeine and catechin are extracted from tea, which has been ingested in large amounts for a long time since ancient times, its safety has been confirmed, and it can be safely consumed. Since it is easy to obtain, it can be manufactured at low cost.

Further, according to the method for producing an internal alcohol metabolism promoter of the present invention, the internal alcohol metabolism promoter having the above composition can be obtained by extracting tea.

[Brief description of drawings]

FIG. 1 is a graph showing the time course of ethanol concentration in blood when caffeine was administered at 50 mg / Kg.

FIG. 2 is a graph showing the time course of acetaldehyde concentration in blood when caffeine was administered at 50 mg / Kg.

FIG. 3 is a graph showing the time course of blood acetate concentration when caffeine was administered at 50 mg / Kg.

FIG. 4 is a view showing a time course of acetone concentration in blood when caffeine was administered at 50 mg / Kg.

FIG. 5 is a diagram showing the time course of ethanol concentration in the liver when caffeine was administered at 50 mg / Kg.

FIG. 6 is a diagram showing the time course of acetaldehyde concentration in the liver when caffeine was administered at 50 mg / Kg.

[Fig. 7] Fig. 7 is a view showing a time-course change in the acetate concentration in the liver when caffeine was administered at 50 mg / Kg.

FIG. 8 is a view showing a time course of the acetone concentration in the liver when caffeine was administered at 50 mg / Kg.

FIG. 9 is a graph showing the time course of blood ethanol concentration when caffeine was administered at 300 mg / Kg.

[Fig. 10] Fig. 10 is a diagram showing the time course of ethanol concentration in the liver when caffeine was administered at 300 mg / Kg.

[Fig. 11] Fig. 11 is a view showing a time course of blood ethanol concentration when a tea extract is administered.

FIG. 12 is a view showing a time course of blood acetaldehyde concentration when a tea extract is administered.

FIG. 13 is a diagram showing a time course of blood ethanol concentration when catechin is administered.

FIG. 14 is a view showing a time course of acetaldehyde concentration in blood when catechin was administered.

FIG. 15 is a view showing a time-course change in blood acetate concentration when catechin is administered.

FIG. 16 is a diagram showing a time course of acetone concentration in blood when catechin was administered.

Continuation of front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI technical indication location (A61K 31/52 31:35) (72) Inventor Shojiro Tsukamoto 4-31-36 Doujida, Nerima-ku, Tokyo

Claims (4)

[Claims] 1. A body alcohol metabolism promoter comprising caffeine as an active ingredient. 2. A body alcohol metabolism promoter comprising caffeine and catechin as active ingredients. 3. Tea is extracted with hot water or an organic solvent or a mixed solution of hot water and an organic solvent, and a polysaccharide is extracted from the extract.
A tea extract obtained by removing proteins and inorganic salts, containing 0.5 mg to 500 mg per kg body weight of a person who ingests caffeine, and 2.5 mg per kg body weight of catechin. An agent for promoting alcohol metabolism in the body, which comprises the tea extract contained above as an active ingredient. 4. A method for promoting alcohol metabolism in a body, characterized in that tea is extracted with hot water or an organic solvent or a mixed solution of hot water and an organic solvent, and polysaccharides, proteins and inorganic salts are removed from the obtained extract. Method of manufacturing agent.