JPH07285881A - Excitometabolic agent for alcohol - Google Patents

Abstract

PURPOSE:To obtain an excitometabolic agent for alcohol, having an activating effect on alcohol dehydrogenase and acetaldehyde dehydrogenase, remarkably excellent in safety and capable of being mass-produced at low cost. CONSTITUTION:A corn protein fraction obtained from a wet milling process is treated with fresh amylase and the resultant treated material is treated with a high-alkaline protease to obtain a hydrolyzed material of the corn protein. This hydrolyzed material is composed of a peptide having 200 to 4000 molecular weight. If this hydrolyzed material is orally administrated, alcohol dehydrogenase and acetaldehyde dehydrogenase are activated. The metabolism of alcohol, therefore, can be improved.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a plant protein, and more particularly to an alcohol metabolism promoter containing a peptide obtained from corn protein as a main component.

[0002]

2. Description of the Related Art It has been conventionally known that an increase in the chance of drinking alcohol causes organ disorders such as acute alcoholism and alcoholism, as well as liver diseases such as fatty liver, alcoholic hepatitis and cirrhosis. . Alcohol and acetaldehyde, which is a metabolite thereof, can be a factor that causes changes in the metabolic system in the living body, and in particular with respect to acetaldehyde, it is said that the acetaldehyde adduct combined with the biological component causes damage to the biological system. In recent years, alcoholism in women has increased, and drinking alcohol during pregnancy causes growth failure of the fetus, especially growth failure of the brain, which has become a social problem. It is said that there are about 2 million alcoholics in Japan.

Alcohol contained in alcoholic beverages (ethanol,
(Hereinafter simply referred to as alcohol) has the effect of elevating the human mind and causing drowsiness, but when the amount of alcohol increases, it becomes so-called drunk. It is considered to be a weak drug that upsets the mind of the person.
However, alcohol also has a nutritional aspect as an energy source. When alcohol is ingested, most of it is converted into acetaldehyde mainly by alcohol dehydrogenase (ADH) existing in the liver, and acetaldehyde is converted into acetic acid by aldehyde dehydrogenase (ALDH). Most of acetic acid is said to be metabolized in vivo.

Alcohol is particularly rapidly absorbed from the stomach when fasting and is then well absorbed in the small intestine. It is said that if you drink alcohol on an empty stomach, it will be completely absorbed in 1-2 hours.
The lethal dose of alcohol poisoning is considered to be 5 mg / ml in blood for humans. Blood and brain alcohol concentrations are distributed at nearly the same level. The activity of alcohol dehydrogenase is related to the concentration of NAD,
If there is a substance that accelerates the oxidation of DH, alcohol oxidation will be promoted and alcohol metabolism will be accelerated.

On the other hand, acetaldehyde plays a role as an intermediate metabolite of alcohol, and causes poisoning symptoms such as headache, nausea, and vomiting such as vomiting. As a method for suppressing the toxicity of acetaldehyde, a method for increasing the activity of acetaldehyde dehydrogenase and a method for decreasing acetaldehyde by administering cysteine or ascorbic acid are known.

From this point of view, if there is a substance that enhances the activity of alcohol dehydrogenase or acetaldehyde dehydrogenase, that is, a substance that has a so-called alcohol metabolism promoting effect, it is very useful for preventing alcoholism and organ damage. it is conceivable that.

Heretofore, as substances promoting alcohol metabolism, for example, fructose, pyruvic acid, D-glyceraldehyde, oxygen, carbon dioxide, 2,4-dinitrophenol, and amino acids such as asparagine, ornithine and cysteine have been reported. (“Alcohol metabolism”, Shinko Medical Publishing Co., Ltd., 1988). They are,
It is said to be due to the fact that it stimulates the redox system of NADH and oxidizes NADH (fructose effect).

Further, in Japanese Patent Laid-Open No. 3-74327, D-cysteine and / or a salt thereof is added to alcohol before ingestion, at the same time,
It is disclosed that when administered after ingestion, it has an action of promoting alcohol metabolism. Similarly, JP-A-3-1974
No. 24 discloses an alcohol metabolism promoter containing ω6 unsaturated fatty acid, particularly γ-linolenic acid as an active ingredient. Further, JP-A-61-166390 discloses a healthy alcoholic beverage containing a saponin component. Furthermore, Japanese Patent Laid-Open No. 05-292918 discloses a young healthy buckwheat powder and a functional health food containing licorice or a licorice extract as an essential component. It is described as having. Furthermore, JP-A-6-14746 discloses a healthy beverage having an effect of promoting alcohol metabolism function, which comprises a glycoside of quercetin, a divalent metal ion and a licorice extract as essential components. .

[0009]

As described above, various substances which are said to have an alcohol metabolism promoting action have been reported, but an alcohol metabolism promoting agent using a corn protein as a raw material has not been known yet. .

Therefore, the object of the present invention is to have an excellent effect of increasing the activity of alcohol dehydrogenase and acetaldehyde dehydrogenase, that is, an effect of promoting alcohol metabolism, which is extremely safe, inexpensive and can be supplied in large quantities. Another object of the present invention is to provide an alcohol metabolism promoter which is useful not only as a medicine but also as a food, and which uses corn protein as a raw material.

[0011]

As a result of various searches for substances that promote alcohol metabolism, that is, substances that enhance the activity of alcohol dehydrogenase and acetaldehyde dehydrogenase, the present inventors have found that they are inexpensive and most common plants. The inventors have found that a peptide obtained by hydrolyzing corn protein, which is a protein, with an alkaline protease has a particularly strong activity to enhance the activity of alcohol dehydrogenase and acetaldehyde dehydrogenase, and completed the present invention.

[0012] That is, the present invention provides an alcohol metabolism promoter containing as an active ingredient a peptide having a molecular weight of 200 to 4,000 obtained by hydrolyzing corn protein with an enzyme.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. The corn protein as a raw material of the alcohol metabolism promoter of the present invention, in the manufacturing process of corn starch, corn protein suspension obtained through wet milling from corn, such as corn gluten meal suspension and corn gluten liquor, Tween and the like which are eluted from the corn protein fraction with 70% hydrous alcohol or alkali are preferably used.

As a preferred method for producing the alcohol metabolism promoter of the present invention, first, these raw materials are previously treated with a raw starch degrading enzyme to decompose and remove starch. According to a preferred embodiment, a pH of about 5 to 6 is adjusted by adding an alkali such as sodium hydroxide, potassium hydroxide or calcium hydroxide to a suspension of corn protein, and a raw starch degrading enzyme such as "Daviase" is added. (Product name, manufactured by Daikin Industries)
0.02 to 0.2 wt% is added to the solid content of the raw material at 50 to 60 ° C.
The mixture is stirred for 3 to 20 hours to react, dehydrated and filtered to decompose and remove starch.

Next, the treated product is treated with a solid content of 5 to 20 wt.
%, Preferably 10 to 15 wt%, and resuspended to this suspension, and an alkali such as sodium hydroxide, potassium hydroxide, calcium hydroxide, etc. is added, and preferably pH 12
After adjusting as above, 0.02 to 0.2 wt% of alkaline protease was added to the solid content of the raw material at 50 ° C, and the amount was 3 at 50 to 60 ° C.
Stir for ~ 20 hours to react. This treatment hydrolyzes the corn protein to an appropriate length.

Examples of the alkaline protease in this case include “Agric. Biol. Chem, 35 (9), 1407” by Hikoshi et al.
~ 1414 "reported by Bacillu
s. No. 221) derived from alkaline protease (manufactured by Meito Sangyo Co., Ltd.), and "esperase 8.OL" and "sabinase" (trade name, manufactured by Novo Co.) derived from an alkaliphilic mutant strain are preferable. These alkaline proteases have an optimum pH for enzyme action of 10 to 12, and have excellent heat resistance,
Usually, it is an endo-type enzyme, and it is an enzyme that hardly produces free amino acids.

The peptide composition which constitutes the active ingredient of the alcohol metabolism promoter of the present invention can be obtained, for example, by the above-mentioned production method. However, in the case of commercialization, the final treatment liquid is concentrated to adjust the pH as necessary. After adjustment, bitterness is reduced by acid treatment, enzyme treatment with amidase, deaminase, etc.,
It is preferable to perform desalting treatment with an ion exchange resin, an ion exchange membrane, a reverse osmosis membrane (RO membrane) or the like, further perform activated carbon treatment, sterilization treatment, and evaporate to dryness to obtain powder. However, depending on the application, the solution may be used as it is.

The alcohol metabolism promoter of the present invention comprises a corn protein hydrolyzed with an enzyme as described above, and is a peptide having a molecular weight distribution of 200 to 4,000. The peptide has a molecular weight of 200 to 2,000.
Is more preferably in the range.

[0019]

[Action] The alcohol metabolism promoter of the present invention exerts an excellent action of enhancing the activity of alcohol dehydrogenase and acetaldehyde dehydrogenase by being orally administered 0 to 30 minutes before alcohol intake, The effect of preventing hangover or hangover can be obtained by easily ingesting it as a drink or food such as tablets immediately before drinking.

The alcohol metabolism promoter of the present invention is
It is considered that continuous ingestion enhances the ability to metabolize alcohol and helps prevent alcoholism and organ damages such as the liver.

[0021]

EXAMPLES The present invention will now be described in more detail with reference to examples. Example 1 Sodium hydroxide was added to 450 L of the protein category obtained from the wet milling step to adjust the pH to 5.5, and 70 g of raw starch degrading enzyme "Daviase" (trade name, manufactured by Daikin Industries, Ltd.) was added to 50 After reacting at ℃ for 5 hours, solid-liquid separation is performed by a filter press to obtain 90 kg of wet cake of corn protein. This wet cake is distilled water 35
Resuspend in 0 L, adjust the pH to 12 by adding sodium hydroxide, add 80 g of highly alkaline protease derived from alkalophilic bacteria (Meito Sangyo Co., Ltd.), and adjust the pH to 9.0 for 20 hours. React. The reaction solution is subjected to solid-liquid separation with a filter press to obtain an enzymatic hydrolyzate of corn protein.

The above hydrolyzate is desalted with an ion exchange resin, decolorized and deodorized with an adsorption resin, treated with activated carbon, sterilized by heating, concentrated and dried to obtain a white powder peptide, that is, the alcohol metabolism promoting of the present invention. Get the agent. This peptide had a molecular weight distribution in the range of 200 to 4,000 and an average molecular weight of 200 to 2,000.

Test Example 1 (Effect of Alcohol Metabolism Promoter 30 Minutes Before Administration on Blood Alcohol and Acetaldehyde Concentration) The test animals were stroke-prone spontaneously hypertensive rats (SHR-SP).
Males, 7 weeks old, 5 animals per group were used. Dissolve the sample in distilled water, orally administer 0.1 g / 100 g body weight equivalent as a sample,
As a control, distilled water was orally administered. Thirty minutes later, 0.1 g / 100 g body weight equivalent of alcohol was orally administered as a 15% aqueous alcohol solution.

Whole blood collected over time was deproteinized with perchloric acid to determine the concentration of alcohol and acetaldehyde in the blood.
The measurement was performed using an analytical reagent "F-kit" (trade name) manufactured by Boehringer Mannheim Yamanouchi Co., Ltd. As a result, changes in the concentration of alcohol are shown in Table 1, changes in the concentration of acetaldehyde are shown in Table 2, and they are collectively shown in FIG.

[0025]

[Table 1] n = 5 mean ± standard deviation, ** is p <0.01, and there is a significant difference

[0026]

[Table 2] n = 5 mean ± standard deviation, * and ** are p <0.0 respectively
5, 0.01 is significantly different

Test Example 2 (Effect of co-administration of alcohol metabolism promoter with alcohol on blood alcohol and acetaldehyde concentration) A sample was dissolved in distilled water to prepare a sample containing 0.1 g / 100 g of body weight and 15% alcohol. 0.1 g of aqueous solution as alcohol
Oral administration was carried out after mixing so that the amount would be equivalent to 100 g body weight.
In addition, as a control, distilled water to which no sample was added and the above alcohol aqueous solution were mixed by the same amount as above and orally administered. Other than that, the test was performed in the same manner as in Test Example 1. As a result, changes in the concentration of alcohol are shown in Table 3 and changes in the concentration of acetaldehyde are shown in Table 4, which are summarized in FIG.

[0028]

[Table 3] n = 5 mean ± standard deviation, ** is p <0.01, and there is a significant difference

[0029]

[Table 4] n = 5 Mean ± standard deviation, *** is p <0.001 with significant difference

Test Example 3 (Effects of alcohol metabolism promoters on alcohol dehydrogenase and acetaldehyde dehydrogenase activities in long-term alcohol-administered rats) The test animals were stroke-prone spontaneously hypertensive rats (SHR-SP).
Male, 7-week-old, 5 animals per group, divided into administration group, control group, and alcohol-free group, and raised for 30 days using alcohol food (Sato Food Industry Co., Ltd.) having the composition shown in Table 5 as feed. did.

In the administration section, the sample was dissolved in distilled water to prepare a 2% aqueous solution, which was freely taken. Also, 80 mg
/ 100g body weight equivalent of alcohol diluted in distilled water, 15%
It was orally administered daily by the sonde method as an aqueous alcohol solution. Further, in the control group, distilled water was freely taken instead of the sample aqueous solution, and the alcoholic aqueous solution was orally administered daily as in the above. Further, in the alcohol-free section, distilled water was freely taken instead of the sample aqueous solution, and the same amount of distilled water was orally administered instead of the alcohol aqueous solution.

[0032]

[Table 5]

When measuring the alcohol dehydrogenase and acetaldehyde dehydrogenase activities, after fasting for 12 hours on the last day of rearing, alcohol was orally administered in the same manner as in Test Example 1. After 30 minutes from the administration, decapitation was performed, and after sufficient blood was discharged, the liver was immediately washed with 0.25 M sucrose buffer (50 ml), and the alcohol dehydrogenase and acetaldehyde dehydrogenase activities in the mitochondrial fraction of the liver fragment were measured. The results are shown in Table 6 and FIG. 3 in comparison with the alcohol unloaded group.

[0034]

[Table 6] n = 5 mean ± standard deviation, * means p <0.05 with significant difference

The activity of alcohol dehydrogenase and acetaldehyde dehydrogenase was measured as follows.

Alcohol dehydrogenase activity measurement Sodium pyrophosphate buffer (0.06M, pH = 8.5) 0.5 ml
And 0.1 ml of ethanol (3M) and 0.1 ml of NAD (1.5 mM)
And 2.0 ml of distilled water were mixed to obtain a reagent. This reagent 2.
To 7 ml, add 0.3 ml of tissue extract to start the reaction.
The absorbance at m is continuously recorded for 3 minutes at 1 second intervals, and the linear absorbance increase ΔAs is obtained. Further, the same operation is carried out using the solvent instead of the substrate to determine ΔAb.

Measurement of acetaldehyde dehydrogenase activity Sodium pyrophosphate buffer (0.05M, pH = 8.8) 0.5 ml
And acetaldehyde (5mM) 0.1ml and NAD (1.0mM)
0.1 ml, pyrazole (0.1 mM) 0.1 ml, and distilled water 2.0 ml were mixed to prepare a reagent. 2.9 ml of this reagent
Then, 0.1 ml of the tissue extract is added to the reaction to start the reaction, and the absorbance at 340 nm is continuously recorded for 3 minutes at 1 second intervals to obtain a linear absorbance increase ΔAs. Further, the same operation is carried out using the solvent instead of the substrate to determine ΔAb.

Calculation of Enzyme Activity The above-mentioned enzyme activities are calculated by the following equation 1.

[0039]

[Equation 1]

From the test results of Tables 1 to 4, in the alcohol metabolism promoting substance administration group, blood alcohol and acetaldehyde concentrations in blood were remarkably lower than those in the control group at 30 minutes before and at the same time as administration of alcohol. The results also show that the activity of the alcohol metabolism-related enzyme is increased, and thus the alcohol metabolism promoting substance of the present invention has an effect of promoting alcohol metabolism.

[0041]

Industrial Applicability As described above, the alcohol metabolism promoting substance of the present invention has the effect of enhancing the activity of alcohol dehydrogenase and acetaldehyde dehydrogenase to promote alcohol metabolism. Ingestion as food such as tablets is expected to have the effect of preventing hangover and hangover. Further, the alcohol metabolism promoter of the present invention is considered to be useful for preventing alcohol dependence and organ disorders such as liver by increasing alcohol metabolism ability by continuous ingestion.

[Brief description of drawings]

FIG. 1 is a chart showing the results obtained in Test Example 1.

FIG. 2 is a chart showing the results obtained in Test Example 2.

FIG. 3 is a chart showing the results obtained in Test Example 3.

Claims (1)

[Claims] 1. An alcohol metabolism promoter comprising a peptide having a molecular weight of 200 to 4,000 obtained by hydrolyzing corn protein with an enzyme as an active ingredient.