JPS6354320A - Anti-alcoholic disease composition - Google Patents

Abstract

PURPOSE:To obtain a food or drug composition having anti-alcoholic disease action, containing alanine and glutamine in specific molar ratio. CONSTITUTION:The aimed substance containing alanine and/or a slat thereof and glutamine and/or a salt thereof in a molar ratio of 1:>=0.001, preferably 1:0.005-0.5. A material in an oral or parenteral form can be provided as a drug and the total weight ratio of alanine, glutamine and/or salts thereof is 0.01-100wt%. A high protein material of a relish taken with SAKE, high fat material, seasoning or drink can be provided as a food form and the total weight ratio of alanine, glutamine and/or salts thereof are 0.01-10wt%.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a food or pharmaceutical composition having an antialcoholic effect.

[Conventional technology]

Alcohol is mainly metabolized in the liver, so if large amounts of alcohol are ingested over a long period of time, damage to the liver, such as fatty liver, liver fibrosis, or liver cirrhosis, will be observed.

Glotoporphyrin preparations, glucuronic acid preparations, and amino acid preparations such as arginine hydrochloride have conventionally been used for the purpose of alleviating or curing such alcoholic liver damage.

In addition to these amino acids, simultaneous administration of alanine and ornithine has been shown to have a strong life-saving effect on mice with acute ethanol intoxication. (Unexamined Japanese Patent Publication Showa 6l-5
0917) [Problems to be solved by the invention] Up until now, the improvement of alcoholism has mainly focused on liver damage,
In particular, the focus was on preventing damage to hepatic parenchymal cells. However, the symptoms caused by alcohol are diverse; even an amount of alcohol that does not cause liver damage can cause hypoglycemia and behavioral depression in humans.

Therefore, the present invention aims to search for substances that are effective in improving alcoholism, using behavior as an indicator.

[Means for solving problems]

The present inventors have observed that when alcohol is administered to dogs, the concentrations of alanine and glutamine, among various plasma amino acids, are significantly decreased. In addition, in an experiment in which powdered alcohol was mixed into the diet of animals and fed for a long period of time, hair loss and weight loss were observed.

Therefore, when various amino acid solutions were selectively ingested, large amounts of alanine and glutamine were ingested, and along with the ingestion of these amino acids, it was observed that hair loss was cured and weight loss was improved.

Therefore, we orally administered alanine and glutamine from a solution in an amount roughly equivalent to the amount that animals ingested in a day, and then intraperitoneally administered alcohol.We found that a mixture of alanine and glutamine had an excellent alcoholism-improving effect. was recognized.

That is, administration of alanine and glutamine improved alcohol-induced behavioral inhibition and promoted the removal of alcohol from the blood, whereas in the group administered with the amino acid mixture in the infusion composition with an isonitrogen amount as the alanine and glutamine mixture, such effects was not observed, and a better effect was observed compared to the administration of an alanine/ornithine mixture (Japanese Patent Application Laid-Open No. 61-50917).

For example, the optimal ratio of the combined use of alanine and glutamine varies depending on the dosage of alanine, and the effect also changes, but in general, the combined use ratio of alanine and glutamine is as follows:
Glutamine is 1/1000 of alanine in molar concentration ratio
It is more than double the mole. Although there is a high upper limit for the amount of glutamine relative to alanine, when the dose of alanine is kept constant, even if the combined dose of glutamine is increased, the effect does not increase proportionally, and on the contrary, there is no effect from both sensory and economic aspects. This will have a negative effect. Therefore, mainly for sensory and economic reasons,
The upper limit of the combination ratio of glutamine to alanine is 10 times the molar ratio. On the other hand, as for the lower limit of the combination ratio of glutamine to alanine, even a small amount of glutamine can be effective, but if it is less than 1/1000 times molar, the effect cannot be expected.

Therefore, the combined ratio of alanine and glutamine is preferably 1:0.001 to 10, and optimally 1:0.05 to 0.5 in terms of molar strength ratio.

Alanine and glutamine can be used in the form of salts or other derivatives as long as they act effectively as alanine or glutamine in vivo.

The composition of the present invention can be provided in the form of a pharmaceutical or food product.

The medicament may be applied orally or parenterally.

The pharmaceutical of the present invention may be provided in a form for oral administration, such as powders, granules, tablets, sugar-coated tablets, capsules, and liquid preparations, and for parenteral administration, such as suspensions, solutions, emulsions,
Ingredients and injection solutions may be mentioned, or a combination of these may also be provided. Diluents that can be combined may be solid, semi-solid, or liquid, such as water, gelatin, sugars, starches, fatty acids, salts thereof, alcohol, fats and oils, Merck, physiological saline, etc., or two or more of these. Examples include combinations of Alanine in the medicament of the present invention,
The proportion of the total weight of glutamine and/or its salts is generally from 0.01 to 100% by weight.

On the other hand, the composition of the present invention can be extremely effectively provided as a food. Preferred food forms are foods that are consumed at the same time as alcohol, or in succession, such as sardines, saki squid, salted roe, mullet, salmon roe, mentaiko, cod roe, caviar, foie gras, rotted milk, tofu, cheese, potato chips, rice crackers, bean sweets, and other high-protein foods, high-fat foods, high-starch foods that are commonly used as appetizers for alcoholic beverages, or yakiniku sauce, Sauces such as sashimi soy sauce, sauce for boiled tofu and cold tofu, dressing and mayonnaise, seasonings such as chili oil, vinegar, table salt, and 1 Japanese sake, beer, shochu, wine, whiskey,
Examples include alcoholic beverages and sports drinks such as prandii, old sake, gin, rum, kanno-ri, guermo, and various cocktails; soft drinks such as tomato juice and other juices; and colas.

The proportion of the total weight of alanine, glutamine and/or their salts in the food of the present invention is generally from 0.01 to
It is 10chi. If it is not desirable to use the amino acid of the present invention at a high concentration from a functional point of view, methods such as encapsulating the amino acid with relatively high melting point oil, protein, starch, etc., or using a masking agent in combination may be adopted. is preferred.

Although the composition of the present invention contains alanine and glutamine as essential active ingredients, it goes without saying that other amino acids may be present in the composition as long as they do not depart from the purpose of the present invention.

The present invention will be further explained below using experimental examples.

(Experiment example-1) SD male (9W age, weight 360-400j')
Six mice were used, and after fasting for 12 hours during the dark period, blood was collected from the subclavian vein, and then a 10% EtOH saline solution was administered (4,2F alcohol/96 body weight-1-p-).

Eight hours after alcohol administration, blood was again collected from the subclavian vein, and plasma amino acid concentrations before and after alcohol administration were measured and compared. Aromatic anoic acid (Tyr *
Ph*, Trp) and branched chain amino acids (IIs.

No significant changes were observed in the plasma concentrations of L@u, Vat) due to alcohol administration. Among the glucogenic amino acids, the plasma concentration of G17 increased due to alcohol administration, and conversely, Aim and Gin 7111 degrees decreased to approximately the pre-alcohol administration value. (Table 2) (Experimental example - ■) SD male mice with an initial weight of 120P were fed a 4.2% thialcohol diet and kept for 200 days.

Since hair loss was observed in 3 animals from 60 bites after the start of experimental food provision, the experimental animals were divided into two groups, and 12 types of animals were added to the normal animal group (n = 3) and the hairless animal group (n = 3). Amino acid solution was provided. 10 days after the start of solution provision, strong preference for Aim and Gin solutions was observed in the normal mouth group. On the other hand, on the 10th day of the hair removal area, Alm
There was no preference for
The case died.

After that, bald animals also prefer Alm like normal animals, and A
With the intake of 1 m, weight loss improved and hair loss was cured.

A1m until the end of the first experiment on the 140th day after the start of solution provision.
The preference for Gin and Gin persists, with a molar ratio of 5
:l Terorita.

(Experiment example -■) Using 40 SD male oysters (10 weeks old), littermates,
Five groups (n=8) were formed so that the rats were evenly distributed among each group, and the rats were raised in a cage with a rotating wheel (the number of rotations of the rotating wheel was recorded using a 7-point sensor and a computer). Preliminary breeding was carried out for 8 weeks until the distance traveled by each animal on the rotating wheel became constant, and then the experiment was started. The animals were fasted for 12 to 3 hours before alcohol administration, and then fed for 2 hours (the CRF-1 powdered food control group was used as a control without alcohol administration, and the other groups were administered 101EtOH saline (4). , 2F alcohol/to 9 body weight 1-p-)
did.

One hour before alcohol administration, control group 1 and control
) solution was administered p, o, and one group received Alm and Gin.
(molar ratio 5:1), Group 2 contained Alm and Orn (molar ratio 5:1), Group 3 contained an amino acid mixture of infusion composition (E
Abbreviated as D, the composition of which is shown in Figure 1) was prepared in a CMC suspension solution using isonitrogen (No. 60z - body weight; in Experiment 1, each animal was given the nitrogen of Ala and Gin that they selectively ingested on the same day (p). -o-)
Blood was collected 14 hours after the alcohol administration, and plasma alcohol concentration and blood sugar level were measured. The distance traveled on the rotating wheel before and after alcohol administration was monitored, and the improvement effects of each amino acid mixture on suppressing behavior caused by alcohol load were compared.

Plasma alcohol concentration 14 hours after alcohol administration is A
The lt・Gin group showed the lowest value, followed by the Alm・Or
n, the ED group showed a lower value compared to the control group 1. (
Table 4) Blood sugar levels after alcohol administration (control group 1) significantly decreased compared to when no alcohol was administered (control ■ group). Blood sugar levels in the ED group also decreased to almost the same level as the control group, but Ala-
The blood sugar levels in the Gin group and the Ala/Orn group were improved to levels close to those in the case where no alcohol was administered (control ■ group).

Significant behavioral inhibition caused by alcohol was observed for one day after alcohol administration, and the amount of running on a rotating wheel was suppressed by about 92 to 97% compared to when no alcohol was administered. After that, the suppression was improved from the second day onwards, especially for Al
In the a-Gin group, a significant suppressive improvement effect was observed compared to the Ala・Orn group, ED group, and control 1 group.

Cloth 1 Composition of amino acid mixture (gD) for infusion composition (H) L-11a 4.5 L-Leu 6.4 L-Lys@HC16,3 L-Me t 4.6 L-Phe
6.2 L-Thr 3.7 L-Trp l・I L-Val 5・0L-Ala
6.4L-Arg@HC
18,0 L-Asp・Na-H2O6,2L-Asp・M
g' 7.3L-Gin
13.7Gly
3.6 L-Hl s @HC1-H203,5L-Pro
4.5L-8ar
8.2L=Tyr
0.8 Total 100.0Table 2 EtO
Plasma amino acid concentration after H administration (μmoJes/fnl)
Immediately before EtOH administration 5hr G17 after EtOH administration
0.145±0.020 0.236±0.0
69Gin 0.520±0.042 0.2
61±0.072Alt 0.521±0.052
0.204±0.081Mal O,28
2±0.024 0.240±0.0171ie
O,137±0.016 0.124±0
．． 010Leu O,158±0.014
0.172±0.006Tyr O,082±0.
008 0.063±0.004ph・0.
059±0.011 0.074±0.007T
rp O,079±0.016 0.060
±0.010 Table 3 [Solution intake per day] 200mM L-Gin 29 28
1450mM L-Hls O0035m
M L-Val 0 0
050 mM L-Arg3
1 5400mM L-Thr O1
345mM L-Phe1
0 0150mM L-Glu・Na
0 2 4200m
ML-8er 2 0
1400mML-L)r+s#Hc1 0
2 1150mM L-Met 1
0 1500mM L-Ala
O3229500'mM Gly
0 0 4Table 4

Claims (1)

[Claims] An anti-alcoholism composition comprising alanine and/or a salt thereof and glutamine and/or a salt thereof at a molar concentration ratio of 1:0.001 or more.