JP2905231B2 - Alcohol absorption inhibitor - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an alcohol absorption inhibitor containing glycyl glycine as a dipeptide as an active ingredient. The formulation according to the present invention is intended to prevent the rise of alcohol concentration in blood by suppressing the absorption of alcohol in the stomach, thereby protecting the living body from the adverse effects of drinking.

(Prior art) Alcohol entering the gastrointestinal tract is rapidly absorbed by the gastric mucosa, 20% and the remainder by the small intestine, of which 5-10% is lost from breath and urine, but more than 90% is metabolized in the liver. In the liver, alcohol is oxidized by two enzyme systems, an alcohol dehydrogenase system and a microsomal ethanol oxygen system, to acetaldehyde, which is then converted to acetic acid by acetaldehyde dehydrogenase. There are two types of acetaldehyde dehydrogenases having different Km values (dissociation constants of substrate enzyme conjugates) (Reference 1). Acetaldehyde dehydrogenase with a low Km value is involved in the oxidation of acetaldehyde. Km for acetaldehyde in human liver
Approximately 50% of those with atypical acetaldehyde dehydrogenase lacking low isozymes were found (References 2 and 3), and blood acetaldehyde concentration after alcohol ingestion in people with atypical acetaldehyde dehydrogenase was lower than in normal people The value is about 17 times higher (Reference 4). In other words, the enzyme does not act until the concentration of acetaldehyde in the blood becomes high, so the oxygen of the acetaldehyde is delayed, and due to its strong chemical reactivity and pharmacological toxic effects, it is mainly circulating such as hot flush, increased heart rate, increased skin temperature, etc. In addition to the pain caused by abnormal increase of the organs, headache, dizziness, drowsiness, nausea, allergic symptoms, etc. appear (Reference 5).

In addition, in recent years, secondary effects of alcohol and its oxide, acetaldehyde, associated with drinking have been reported as follows.

(1) By inhibition of nerve cell membrane by alcohol (Na ⁺
+ K ⁺ ) -ATPase activity is suppressed, and membrane fluidity is increased due to disturbance of phospholipid sialic chains in the hydrophobic core of the membrane (Reference 6).

(2) Deviation of enzymes from necrosis of pancreatic cells due to direct metabolic damage to pancreatic exocrine cells due to alcohol and accompanying breakdown of pancreatic duct branch (Reference 7).

(3) Hypertension due to promotion of catecholamine secretion by acetaldehyde, endocardial thrombus formation based on increased platelet aggregation, endocardial myocardial sclerosis, and the like (Reference 8).

(4) Various metabolic abnormalities due to reduced acetaldehyde oxidizing ability of liver mitochondria, rotation of the citric acid cycle, and inhibition of fatty acid oxidation (Reference 9).

In order to drink alcoholic beverages healthy, it is desirable to reduce or neutralize the above-mentioned adverse effects on living organisms due to the toxicity of alcohol and its metabolite, acetaldehyde. From these viewpoints, various substances have been reported as follows, which reduce the concentration of alcohol or acetaldehyde in blood or suppress the toxicity of acetaldehyde.

Acetaldehyde trapping agent (1) D-penicillamine (Reference 10).

(2) L-cysteine, SH compounds such as DL- homocysteine, vitamin B ₁ and its derivatives and ascorbic acid (Reference 11).

(3) L-methionine (Reference 14).

Metabolic promoter (4) Egg white hydrolyzate (mixture of various amino acids) (Reference 1)
2).

Toxicity reducer (5) L-α-alanine (Reference 13).

(Problems to be Solved by the Present Invention) The present inventor has found that by suppressing the absorption of alcohol from the digestive tract, the concentration of alcohol and acetaldehyde in the living body can be prevented from increasing, and acute toxicity or sickness caused by alcohol consumption, or various Considering that the side effect can be suppressed, various substances capable of suppressing such alcohol absorption were searched.

(Means to solve the problem) As a result, glycyl glycine, a kind of dipeptide, has the effect of suppressing alcohol absorption from the stomach into the blood. Therefore, if glycyl glycine is administered,
The present inventors have found that an increase in blood alcohol concentration can be prevented and the living body can be protected extremely effectively, and the present invention has been completed.

That is, the present invention provides an alcohol absorption inhibitor containing glycyl / glycine as an active ingredient.

Glycyl-glycine, which is an active ingredient of the present invention, is a simple dipeptide containing no asymmetric carbon, and is synthesized (Reference 1).
5, 16, 17, 18) or can be easily obtained from commercial products. Further, it is tasteless and odorless, and can be used with confidence without impairing the sensory surface such as taste and smell even when it is blended in various preparations. In the preparation of the present invention, citric acid, organic acids such as malic acid, inorganic salts such as sodium chloride and potassium chloride, vitamins, other amino acids,
Extracts of various crude drugs, fragrances and the like can be blended.

As the form of ingestion, any of powders, granules, tablets, capsules and the like can be used in addition to liquids.

Even if you drink the same amount of alcohol, the rate of absorption and metabolism
Due to differences in constitution, etc., the individual difference is very large, and the effective amount of glycyl / glycine cannot be clearly defined. However, in order to sufficiently exert the effect of suppressing alcohol absorption, a single dose of 0.5 to 5.0 g It is desirable to be within the range.

There is no particular limitation on the time of taking, and it can be taken before or at the same time as alcohol ingestion to prevent sickness and hangover, and taken after alcohol ingestion to prevent sickness and hangover.

Hereinafter, the present invention will be described in more detail with reference to Test Examples and Production Examples.

Test Example 1 (1) Experimental animal: ddY conventional mouse, male, 4
~ 5 weeks old.

(2) Experimental method Alcohol (ethyl alcohol) was diluted to 20% with distilled water. Further, commercially available glycyl / glycine was dissolved in distilled water and subjected to a test as a 5 to 20% solution.

The mice were divided into a group administered with alcohol alone (control group) and a group administered with alcohol and glycyl / glycine (5%, 10%, 20%).

First, glycyl-glycine (5-20% aqueous solution
ml / Kg was administered, and one hour later, alcohol (2 ml / Kg as a 20% aqueous solution) was administered. In the control mice, distilled water (20 ml / Kg) was used instead of the test drug (glycyl / glycine)
Was administered. One hour after the administration of alcohol, the animals were anesthetized with ether and opened, and blood samples were collected from the abdominal vena cava. The stomach was also excised with its contents at the same time. The stomach was weighed, homogenized in purified water for 1 minute, and then made up to 40 ml with purified water. 120 µ of perchloric acid was added to 20 µ of each of the collected blood and the homogenized solution, and the mixture was stirred, centrifuged at 3000 rpm for 5 minutes, and the supernatant was used as blood and stomach samples. The alcohol concentration in blood or stomach was measured by an enzyme method (Reference 19). In addition, Student's t test was used as an effect criterion.

(3) Test results The concentration of alcohol in blood and stomach by enzyme method
Shown in the figure. That is, the blood alcohol concentration of the glycyl / glycine administration group decreased with the increase in the dose,
The glycyl / glycine 20% solution showed a significant suppression of 84% (p <0.001). On the other hand, the alcohol concentration in the stomach showed an inverse correlation. It was shown that administration of this drug inhibited the absorption of alcohol and suppressed the blood alcohol concentration to a low level. This effect was dose dependent.

Production Example 1 [Solution] Composition Glycyl / Glycine 5000 mg Vitamin C 600 mg Citric acid 200 mg Fragrance 0.4 ml Combine the above ingredients and add water to make the total amount 100 ml.
Also, carbon dioxide gas may be blown into this to make a carbonated drink.

Production Example 2 [Granules / Powder] Glycyl / Glycine 1000 mg Lactose 90 mg Oxypropylcellulose 10 mg Total 1100 mg After mixing at the above ratio, add a small amount of water, knead with a kneading machine, sieving and drying. Wrap. The above amount is taken as one dose unit.

Production Example 3 [Tablets / Capsules] Glycyl / glycine 300 mg Lactose 96 mg Magnesium stearate 4 mg Total 400 mg Glycyl / glycine and lactose are mixed in the above ratio and tableted . In the case of a capsule, this is pulverized, mixed with magnesium stearate, and filled with a capsule filling machine. 1
Take 2 capsules or more per serving.

Literature 1 Yoshiro Matsuda et al .: Alcohol metabolism and effects on living organisms: Med
icina, vol.23 No.3: 388-390,1986.

2 K. Harada: Pharmacogenetic significance of acetaldehyde dehydrogenase polymorphism: alcohol metabolism and liver research report, 209-214,
1983.

3. Ryuichi Kanayama, Yoshiro Matsuda, Shujiro Takahashi et al .: Localization of human liver acetaldehyde dehydrogenase isozyme and its etiological significance: Alcohol metabolism and liver, vol.2: Report of alcohol metabolism and liver study group, 223-234 , 1983.

4 Harada, S .: Aldehyde dehydrogenase deficiency as
cause of facial frushing reaction to alcohol in J
apanese: The Lancet. 31: 982.1981.

5 Mizoi, Y., Ijiri, I., Tatsuno, J. et al .: Relationshi
p between facial flushing and blood acetaldehyde l
evels after alcohol intake: Pharmacol.Biochem.Beha
v., 10: 303-311,1979.

6 Nakao, A .: Pharmacology of alcohol: Diagnosis and treatment, vol.7
3 No. 5: 978 to 981,1985.

7 Kuniji Kojima: Alcoholic Pancreatitis: Medicina.vol.13 N
o. 10: 1390-1392,1976.

8. Hideo Takezawa, Hideo Nishikawa et al .: Alcoholic Cardiomyopathy 2
An autopsy case: Research and development group for specific cardiomyopathy, a disease specified by the Ministry of Health and Welfare, Showa
58 report, 169-176, 1984.

9 Hiromasa Ishii: Biochemical mechanism of the establishment of alcoholic fatty liver and hepatitis: Japanese clinical practice, vol.34 No.11: 3168-3173,19
76.

10 Nagasawa, HTet al.; Lowering of Ethanol-Deriv
ed Criculating Blood Acetaldehyde in Rats by D-Pe
nicillamine: Life Sciences vol.20: 187-194,1977.

11 Isao Morii, T. Tsurumi et al .: Effects of various drugs on acute toxicity of acetaldehyde (I), SH compounds and vitamins
Effect and combination effect of alcohol: alcohol research vo
l.11 No.2: 12-24,1976.

12 Peter, CJ, Analytical Biochemistry 87, 116-12
4,1977.

13 Kenji Hara, Satoshi Tsujita: Promoters of alcohol metabolism in vivo:
Published patent publication. 58-157724,1983.

14 Yoshihide Suwa, Noriko Kiyota and others: Toxicity inhibitors for aldehydes:
Published patent publication. 61-134313,1986.

15 Schott, H. et al., J. Org. Chem. 12, 490 (1947).

16 Zervas, L. et al., J. Am. Chem. Soc. 78, 1359 (195
6).

17 Sheehan, F., J. Am. Chem. Soc. 71, 1856 (1949).

18 Weygand, R., Ber. 88, 26 (1955).

19 Tabakoff, B. et al., Methionine Lowers Circulatin
g Levels of Acetaldehyde after Ethanol Ingestion.1
3 (2), 164, 1989.

[Brief description of the drawings]

FIG. 1 is a graph showing the effect of glycyl glycine on blood and gastric alcohol concentrations.

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁶ , DB name) A61K 38/05 CA (STN)

Claims (2)

(57) [Claims] An alcohol absorption inhibitor comprising glycyl / glycine as an active ingredient. 2. The preparation according to claim 1, which can be administered orally.