JPH04342528A - Agent for promotion of alcohol metabolism and acetaldehyde metabolism - Google Patents

Abstract

PURPOSE:To provide the subject high-safety medical drug of much practical use, containing kinds of vitamin B2 and kinds of vitamin B6 as the active components and showing a strong effect. CONSTITUTION:Kinds of vitamin B2 such as riboflavin, flavin adenine dinucleotide and riboflavin phosphate in combination with kinds of vitamin B6 such as pyridoxine, pyridoxamine and pyridoxal phosphate are used as the active components. If kinds of vitamin C, cysteines or kinds of vitamin B1 are further added thereto, further improved effects are shown. As dosage of respective components per one time, kinds of vitamin B2, kinds of vitamin B6, kinds of vitamin C, cysteines and kinds of vitamin B1 are 5-100mg, 10-300mg, 200-500mg, 50-500mg and 5-200mg, respectively. Administration after or before drinking alcoholic drink is recommendably carried out in one-several times after or before the drinking.

Description

Detailed Description of the Invention [0001] [Industrial Application Field] The present invention relates to an alcohol metabolism and acetaldehyde metabolism promoter characterized by containing vitamin B2s and vitamin B6s as active ingredients. . [Prior Art] Vitamin B2 and/or vitamin B6 are widely used as vitamin preparations, and their efficacy and effects are mainly for angular cheilitis, cheilitis, stomatitis, glossitis, eczema, dermatitis, It is said to be a good supplement for rashes, sores, acne, rough skin, red noses, red eyes, itchy eyes, as well as during pregnancy, breastfeeding, and when physical strength declines during or after illness. These vitamins may also be given as supplements to treat deficiencies caused by long-term alcohol consumption. However, when vitamin B2 and vitamin B6 are used together, they significantly promote both alcohol metabolism and acetaldehyde metabolism, and are effective as prevention agents for preventing severe drunkenness, promoting sobering up, and preventing and treating hangovers. is not known to exhibit. In addition, L-ascorbic acid and L-cysteine have a protective effect against the anesthetic and lethal effects of acetaldehyde, and it is said that a formulation consisting of a combination of L-ascorbic acid, L-cysteine, and thiamine hydrochloride is particularly effective. Reported by Ruberto Splins et al. [Agents and Actions, No. 5]
/ vol. 2, pp. 169-173 (1975)]. Furthermore, a combination of vitamin C, vitamin B1 and vitamin B6 is also known to reduce blood alcohol levels (European Patent Publication No. 288610). However, it promotes both alcohol metabolism and aldehyde metabolism,
At present, there are almost no pharmaceuticals that are highly effective, safe, and highly practical. [0003]Problems to be Solved by the InventionAlthough alcohol is said to be the best medicine, alcohol has many harmful effects on the human body, and has even become a social problem. By drinking,
Symptoms such as drunkenness, hangover, and hangover appear, and these symptoms are said to be caused by the central depressant effect of ethanol and acetaldehyde produced when ethanol is metabolized. However, there is currently no specific drug for improving or preventing the various symptoms caused by ethanol and acetaldehyde. Therefore, it is desired to develop a drug that promotes alcohol metabolism and acetaldehyde metabolism, is highly safe, and is highly practical. [Means for Solving the Problems] The present inventors have conducted extensive research on compounds that promote alcohol metabolism and acetaldehyde metabolism and have the effect of preventing and improving various symptoms associated with drinking, such as drunkenness, hangovers, and hangovers. As a result, they found that a combination of vitamin B2 and vitamin B6 has a strong effect, is extremely useful, and has high practicality, and has completed the present invention. Next, the present invention will be explained in detail. The present invention has a formulation that combines vitamin B2 and vitamin B6 to promote alcohol metabolism and acetaldehyde metabolism, but also contains vitamin C and cysteine in addition to vitamin B2 and vitamin B6. A further enhanced effect can be exerted by using a formulation containing vitamin C, cysteine, and vitamin B1 in addition to vitamin B2 and vitamin B6. The vitamin B2 species used in the present invention may be any substance that exhibits vitamin B2 action in vivo, such as riboflavin,
Mention may be made of flavin adenine dinucleotide and riboflavin phosphate, as well as various physiologically acceptable esters thereof (such as riboflavin butyrate) and various salts thereof. In addition, vitamin B6 used in the present invention
Substances that exhibit vitamin B6 action in vivo may be used, and include, for example, pyridoxine, pyridoxamine, pyridoxal phosphate, and various physiologically acceptable esters and salts thereof. Examples of vitamin C include L-
Mention may be made of various physiologically acceptable salts such as the sodium salt of ascorbic acid or L-ascorbic acid and the calcium salt of L-ascorbic acid. As cysteines, it is possible to use, for example, physiologically acceptable salts such as L-cysteine or L-cysteine hydrochloride and L-cysteine sodium salt, and it is also possible to use glutathione. . Vitamin B1 may be any substance that exhibits the action of vitamin B1 in vivo, such as thiamine, thiamine hydrochloride, and disulfide thiamine, as well as various physiologically acceptable esters and salts thereof. can be mentioned. In the above-mentioned composition of the present invention, various vitamins such as vitamin E, pantothenic acid or its salts, pantethine, nicotinic acid amide, vitamin B12, etc.; choleretic agents; sugars; and Japanese and Chinese herbal medicines may be appropriately blended. be able to. [0006] The composition of the present invention can be provided in the form of a pharmaceutical or food product, and can be administered both orally and parenterally. Forms in which the composition of the present invention can be provided include commonly known dosage forms, for example, for oral administration,
Tablets, powders, granules, dragees, capsules and liquids, etc.
Parenteral administration includes suspensions, solutions, emulsions, ampoules and injections, and combinations of these can also be provided. At the time of formulation, additives commonly known in the field of formulations can be used as appropriate. [0007] Furthermore, the administration method, dosage and frequency of administration of the composition of the present invention are appropriately selected depending on the symptoms of the patient, and the dosage of each component can generally be selected within the following ranges. o Vitamin B2 types: approx. 5 mg to 100 mg/day o Vitamin B6 types: approx. 10 mg to 300 mg/day o Cysteine types: approx. 50 mg to 500 mg/day o Vitamin C types: approx. 200 mg to 5000 mg/day o Vitamin B1 types: approx. 5 mg to 200 mg/day Take the daily dose of 1 dose before drinking alcohol, after drinking alcohol, or before and after drinking alcohol.
-Administration may be divided into several doses. Next, the effects of the composition of the present invention will be explained by the expression of pharmacological effects upon administration of ethanol or acetaldehyde. The test was conducted using Test Methods 1 and 2. (1) It is a well-known phenomenon that alcohol causes paralysis of the limbs and a staggered gait. Even in animals, when a certain amount of ethanol or aldehyde is administered, the limbs become paralyzed and the gait becomes abnormal, which is not normal. You will not be able to hold on to metal rods that you can hold on to. Promoting ethanol metabolism and acetaldehyde metabolism and shortening the time of limb paralysis shows an effect of promoting sobriety during drinking, and is also important for the prevention and treatment of hangovers and bad intoxication. Ethanol metabolism and acetaldehyde metabolism promoting effects were investigated by the following test method 1. (2) Generally, one of the symptoms of a hangover caused by drinking alcohol is said to be abnormalities in gastrointestinal function such as gastrointestinal discomfort and loss of appetite. One of the common methods to measure gastrointestinal function in animals is to measure the intestinal charcoal transport ability, and since ethanol impairs and reduces the intestinal charcoal transport ability in mice, the effect of drugs on this is important. was investigated in Test Method 2. Below, those test methods are specifically described. Note that the dosage of each component used in the test is as shown in Table 1. In the case of doses other than these, the doses are written in parentheses (Table 7, Table 8). In addition, the ingredients of the formulations in Tables 2 to 9 are indicated by the abbreviations shown in Table 1. [Table 1] Each component used and its dosage ────────────────
──────────────────────
Ingredients
Abbreviation
Dose

(mg/kg)
────────────────────────
────────────── Riboflavin
VB2
100 Riboflavin butyrate
VB2but 1
00 Pyridoxine/HCl
VB6
200 L-ascorbic acid
VC
500 L-cysteine・HCl・
H2O Cys
300 Thiamine hydrochloride
VB1
200───────
──────────────────────────
──── (1) Test method 1 (ethanol metabolism and acetaldehyde metabolism promoting effect) DDY male mice (approximately 5 to 6 weeks old) are fasted for approximately 18 to 20 hours, and the test drug is orally administered. . Test drug administration 90
Minutes later, 3.1 ml/kg of ethanol or 200 mg/kg of acetaldehyde is administered intraperitoneally. When mice are administered ethanol or acetaldehyde, their limbs become paralyzed and they are unable to grasp a metal rod with a diameter of 1.5 mm, but they recover over time and are able to grasp. The paralysis time was measured as the time until the animal was able to grasp with three or more paws, including the two front paws. Note that ethanol and acetaldehyde were mixed with an appropriate amount of saline solution and administered. In addition, to the control group, only saline solution was administered at 0.1 ml per 10 g of mouse body weight. The results are shown in Tables 2 to 8. [Table 2] [Table 3] Effect of drug administration on the quadriplegic effect of acetaldehyde in mice ──────────
──────────────────────────
─ Prescription
Number of mice used Average paralysis time (seconds)────────────────────
──────────────── Control group

16 372±15.6
VB2but+VB6
15
284±18.5**────────────────
──────────────────────
t-te
st **P<0
．． [Table 4] [Table 5] [Table 6] Effect of drug administration on the quadriplegic effect of acetaldehyde in mice ──────────
──────────────────────────
Prescription
Number of mice used Average paralysis time (seconds) ──────────────────────
──────────────── Control group

12 434±37
Cys+VC+VB1
12
371±24 Cys+V
C+VB1+VB2but+VB6 12
313±12**
────────────────────────
────────────
t-test
**P<0.01 [0016] [Table 7] Effect of drug administration on the quadriplegic effect of ethanol in mice ────────────
────────────────────────
Prescription (dosage)
Number of mice used Average paralysis time (minutes)
(mg/kg)

──────
──────────────────────────
────── Control group
12
141±6.3C
ys+VC+VB1
12 126±8.
7 Cys+VC+VB1+VB2
but+VB6 12
96±11.3** Cys+VC
+VB1+VB2but+VB6 12
94± 9.9**
(160) (25) (20)
(100)
───
──────────────────────────
────────
t-test **P<
0.01 [Table 8] (2) Test method 2 After fasting male ddy mice (approximately 5 to 6 weeks old) for approximately 16 to 18 hours, the drug was orally administered, and the drug was administered for 1 hour. Afterwards, 4 ml/kg of ethanol is intraperitoneally administered. Ethanol administration 1.
After 5 hours, charcoal powder suspended in 0.25 ml of gum arabic liquid is orally administered. 40 minutes after administration of charcoal powder, the intestine of the mouse was removed and the length from the pylorus of the stomach to the tip of the charcoal powder (A),
and measure the length (B) from the pylorus of the stomach to the cecum,
Calculate the intestinal charcoal transport rate according to the following formula. The charcoal powder transport rate shows an average value of about 50 to 60% when ethanol is not administered (normal case), and decreases to a value of about 20 to 30% when 4 ml/kg of ethanol is intraperitoneally administered. Table 9 shows the results when the drug was administered at this time. [0019] [Table 9] [0020] Judging from the above results comprehensively, it was found that the present invention exerts an effect of promoting alcohol metabolism and acetaldehyde metabolism by using vitamin B2 and vitamin B6 in combination, Furthermore, a formulation containing vitamin C and cysteine in addition to vitamin B2 and vitamin B6, or a formulation containing vitamin C, cysteine and vitamin B1 in addition to vitamin B2 and vitamin B6. It can be seen that by doing so, a further enhanced effect is exhibited. Furthermore, the formulation containing vitamin B2 and vitamin B6 shows excellent effects and is also useful for preventing and treating gastrointestinal symptoms caused by hangovers caused by drinking alcohol. [Example] Next, formulations will be shown as examples, but the formulations are not limited to these. Example 1 Capsules having the following composition per capsule can be manufactured by known means. Example 2 Fine granules having the following composition per package can be produced by known means. Example 3 Fine granules having the following composition per package can be produced by known means. [0024] Effect of the invention: Vitamin B2 and vitamin B6 of the present invention
A combination of these drugs can promote alcohol metabolism and acetaldehyde metabolism, but in addition,
The formulation contains vitamin B2 and vitamin B6 as well as vitamin C and cysteine, or
Vitamin B2 and B6 as well as vitamin C,
By using a formulation containing cysteine and vitamin B1, a further enhanced effect is exhibited. Therefore, the present invention is useful for the prevention and treatment of hangovers and hangovers.

Claims (3)

[Claims] [Claim 1] Vitamin B2 and vitamin B
An alcohol metabolism and acetaldehyde metabolism promoter characterized by containing Group 6 as an active ingredient. [Claim 2] Vitamin B2 and vitamin B
The alcohol metabolism and acetaldehyde metabolism promoter according to claim 1, which further contains vitamin C and cysteine in the 6th class. [Claim 3] Vitamin B2 and vitamin B
The alcohol metabolism and acetaldehyde metabolism promoter according to claim 1, which further contains vitamin C, cysteine, and vitamin B1 in category 6.