JPH04124133A - Alcohol metabolism promoter - Google Patents

Abstract

PURPOSE:To obtain an alcohol metabolism promoter reducing alcohol concentration in blood and acetaldehyde increased by drinking, comprising an acyloxyalkanoylcholine sulfonate derivative as an active ingredient. CONSTITUTION:An alcohol metabolism promoter comprises a compound shown by the formula (R<1> and R<2> are 1-5C alkyl; X is sulfonic acid residue; (n) is the same number as that of sulfonyloxy of sulfonic acid residue and is 1-4) known to have activating action on motility function of digestive organ, such as bis(2-trimethylammonioethyl-alpha-acetoxypropionate)-naphthalene-1,5-d isulfonate as an active ingredient. The metabolism improver is extremely useful for improving symptoms such as drunkenness, drunken sickens or hangover followed by drinking and the dose is 75-500mg/day usually by oral administration and the metabolism improver is administered once or dividedly several times.

Description

Detailed Description of the Invention [Industrial Field of Application] The present invention relates to the general formula [I], which is known to have a gastrointestinal motor function activation effect, [wherein R and R2 are the same or different] , a lower alkyl group having 1 to 5 carbon atoms; ” is an acyloxyalkanoylcholine sulfonate.

: Jubei's technology 1 The compound represented by the general formula [I] is said to have the effect of activating the gastrointestinal tract VJ function (Japanese Patent Publication No. 52-214
No. 90, No. 53-37334 and No. 55-1251
No. 1), nothing is known about its alcohol metabolism promoting effect.

;Problems to be solved by the invention]Although it is said that ``alcohol is the best medicine,'' there are many harmful effects of alcohol, and it has various effects on the human body.

Drinking alcohol causes symptoms such as drunkenness, sobriety, and a hangover. These symptoms are said to be due to the central depressant effect of ethanol and acetaldehyde produced when ethanol is metabolized.

However, there is no specific drug for improving the symptoms caused by ethanol and acetaldehyde, and it is generally recommended to take vitamins and/or amino acids after drinking alcohol.
Currently, we are trying to alleviate the unpleasant symptoms.

In addition, from Jubei, prevention of severe drunkenness, promotion of drunkenness, prevention and treatment of hangovers, and prevention and treatment of alcohol consumption.
Eleven studies have been conducted and various substances have been investigated with the aim of improving the many harmful effects associated with drinking, such as treatment. However, very few have actually been put into practical use as pharmaceuticals, and there is a desire for the development of highly practical pharmaceuticals that promote alcohol metabolism.

[Means for Solving the Problems] As a result of intensive research into compounds that promote alcohol metabolism and are highly practical, the present inventors found that a compound represented by the formula fI] The present invention has been completed based on the discovery that this compound is extremely useful and highly practical for improving various symptoms associated with drinking, such as drunkenness, nausea, and hangovers, by promptly promoting metabolism.

Next, the present invention will be explained in detail.

In the compound represented by 2N], examples of the lower alkyl group having 4 to 5 carbon atoms for R1 and R- include methyl, ethyl, propyl, butyl and pentyl.

Examples of the sulfonic acid residue of X include anions formed when protons are removed from monosulfonic acid, disulfonic acid, trisulfonic acid, and tetrasulfonic acid. and alkanesulfonic acids such as ethanesulfonic acid;
Arenesulfonic acids such as benzenesulfone, toluene-2-sulfonic acid, toluene-4-sulfonic acid, naphthalene-1-sulfonic acid and naphthalene-2-sulfonic acid; aralkanesulfonic acids such as phenylmethanesulfonic acid; cyclohexyl Sulfuric acid: camphor-3-
Sulfonic acid; camphor-8-sulfonic acid; and camphor-10
Examples of disulfonic acids include benzene-1,3-disulfonic acid, toluene-3,5-disulfonic acid, and naphthalene-3,5-disulfonic acid.
Arene disulfonic acids such as 1,5-disulfonic acid, naphthalene-2,6-disulfonic acid and naphthalene-2,7-disulfonic acid, or trisulfonic acids such as benzene-1,3,5-trisulfonic acid, etc. sulfone ri
and arene trisulfonic acids such as naphthalene-1,3.5-trisulfonic acid 1!2 or, as tetrasulfonic acids, arene tetrasulfonic acids such as naphthalene-1,3.5.7-tetrasulfonic acid. can be mentioned. Further, the alkyl group and aryl group of these sulfonic acids may be substituted with various substituents.

- Among the compounds represented by the formula [I], preferred examples include, for example, R1 and R2 are methyl groups,
X is a 1,5-naphthalenedisulfonate group, and
is 2 (hereinafter referred to as
It is called acladonium navadicylate. ).

-Specifically, the compound represented by the formula [1] is
-1251 and JP-A-58-180463@.

The compound represented by the general formula [I] of the present defense may include L-ascorbic acid, @acid thiamine, fursulthiamine, bisbenziamine, pyridoxine hydrochloride, calcium pan-1-thenate, nicotine diamide, etc. , riboflavin and tocopherol acetate; L-
Amino acids such as cysteine and L-alanine, Nijiyoukyou, Fennel, Soydula, Oven, Hops,
Herbal medicines for stomach health such as Chinese cabbage, Chinese cabbage, clove, carrot, Japanese assemblage, licorice, site, bittern and gentian: Antacids such as magnesium silicate, synthetic and dorotalcite, magnesium liquefaction and sodium bicarbonate; urtude oxycholic acid , cholic acid, bile powder, and cholate, as well as digestive enzymes such as starch-digesting enzymes, protein-auto-digesting enzymes, fat-digesting enzymes, fiber-digesting enzymes, or complex enzymes thereof (e.g., biodiastase, etc.). Can be blended.

The compound represented by formula 'I] of the present invention can be made into commonly known dosage forms such as tablets, powders, granules, or capsules. Furthermore, tablets, powders, granules, and the like can be formulated by methods such as granulation or film coating according to conventional methods. In formulation, excipients such as corn starch, lactose, saccharose, microcrystalline cellulose, mannitol, fructose or sorbitol, lubricants such as talc or magnesium stearate, are added to the formulation. The formulation can be formulated using binders such as starch, polyvinylpyrrolidone, methylcellulose or hydroxypropylcellulose, or antifilm agents such as hydroxypropylmethylcellulose or hydrogenated castor oil.

In addition, - the administration method, administration m, and administration frequency of the compound represented by formula [I] are selected depending on the patient's symptoms, but usually oral administration is performed for 75 to 500 m and 7 days once to several times. It can be administered separately.

Next, the effects of the compound represented by the formula [I] will be explained using the blood concentrations of ethanol and acetaldehyde when ethanol is administered.

(1) Test method ICR male mice (7 mice per group, body weight: 22-25 mm) were orally administered with 150 μg/kg of Napadisil dissolved acladonium dissolved in physiological saline under non-fasting conditions. As a control, only physiological saline solution was administered. 40 minutes later
% ethanol physiological saline solution 4 g/ka was administered intraperitoneally,
Thirty minutes later, blood was collected, and the concentrations of ethanol 5 and acetaldehyde in the blood were measured by gas chromatography (headspace method).

The results are shown in Table-1.

(Leaving space below) Table 1 (2) Effect on hangover symptoms after drinking Alcoholic drinks (beer, whiskey, sake, etc.) were given to volunteers
The participants were asked to drink ``more than normal'' based on their own judgment. After drinking alcohol, people who exhibited symptoms of hangover were asked to take the fine grains of Example 6 or 7, and answers were obtained regarding the improvement effect on the main subjective symptoms.

The results are shown in Table-2.

Table 2 As is clear from the above results, napadisil υ acradonium has an effect of promoting metabolism in the metabolism of ethanol, and has an effect of curing various symptoms of a hangover.

[Effects of the Invention] Therefore, - the compound represented by formula [1] reduces the blood alcohol concentration and acetaldehyde concentration that increase due to drinking, is useful as an alcohol metabolism promoter, and improves various symptoms associated with drinking. Therefore, it can be used as a medicine.

[Example] Next, the present invention will be explained with reference to Examples, but the present invention is not limited thereto.

Example 1 Capsules having the following composition containing 50R1j/capsule as navadicil-awakened acladonium can be manufactured by known means.

Acladonium Navadisylate 50m3 Corn Starch 240mg Hydroxybrobyl Cellulose Brng Stearin Magnesium 2mg Per Capsule
300 mg Example 2 Granules having the following composition containing 1 υomg/g of acladonium napadisylate can be produced by known means.

Acladonium Navadisylate 100zy Mannitol 880mg Hydroxypropylcellulose 2omg000my Example 3 Tablets with the following composition containing 7 tablets of 50mg Navadisylate Acladonium can be manufactured by known means.

Navadisil Shun Acladonium 50In! j Corn starch 100my lactose
113fflJ Crystalline Cellulose 10hy Hydroxypropyl Cellulose 1 Omg Example 4 A fine granule having the following composition containing 50 mg/g of navadicyl acladonium can be produced by known means.

Acladonium napadisylate 50mg cinnamon powder 110my bittern powder 30mg ginger powder 30 ■ fenugreek powder
30m91 corn starch
250ml lactose
250mg crystalline cellulose
Page 200iy Example 5 (1) Acladonium Navadisylate 5 Dra
g milk iq 190ffl
J refined white 1! 250mg
10 mg00zy of hydroxypropylcellulose is made into fine particles by centrifugal fluid granulation.

(2) C7 Scorbic Acid 50071
1F Mannitol 485 mg and hydroxypropyl cellulose 15 mg000 my were wet-kneaded and made into fine particles by extrusion granulation.

(3) Above (Seasonal Acladonium Napadisylate Fine Granules 50
0iy and (2) Noshi-Ascorgonic Acid Fine Granules 330
mg are mixed to produce a fine granule consisting of two fine particles.

Example 6 (1) Achradonium navadisylate 5om3 Lactose 190iy Refined sucrose 250 = dihydroxypropyl cellulose 1om300mg @ Made into fine granules by centrifugal flow granulation method.

(2) L-ascorbine li 500/
I+, 9 mannitol 485m
3-droxypropylcellulose 15mg100
0#I9 is wet-kneaded and made into fine particles by crushing and granulation.

(3) Hop extract 265m3 Licorice extract 10f4 Mannitol 1430mg 25 29m=3830m3 is wet-kneaded with polyvinylpyrrolidone and made into fine particles by crushing and granulation.

(4) Acladonium Navadisylate Fine Particles 5 of (1) above
00iy, (2) Noshi-ascorbic acid fine granules 330 r
ttg and 610 grams of the hop-containing fine grains of (3) are mixed to produce a fine granule consisting of three fine grains.

Example 7 (1) Acladonium navadisylate 150#lJ
Lactose 519m! 1 Refined white sugar 694.5 m 9 Hydroxypropyl cellulose 25.5 #fg Hydrogenated castor oil 100 η Hydroxypropyl methylcellulose 111 Ig 500 gj S: Finely granulated by a continuous flow granulation method.

(2) Biodiastase (Ohno Pharmaceutical> 150i
y Keihi powder 60ty) bittersweet powder 30mg ginger powder 30η fenugreek powder
30η Oubaku powder
28.5M! Licorice end
300Itg Lottery 1
．． 5II! I lactose 78
30 815 to 5#j polyvinylpyrrolidone
00Iyl was wet kneaded and made into fine particles by extrusion granulation.

(3) Acradonium napadisylate fine particles 5 of (1) above
00IR1J and (2) enzyme/crude drug fine granules 5QOη are mixed to produce a fine granule consisting of 21a grains.

Claims (4)

[Claims] (1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ “In the formula, R^1 and R^2 are the same or different,
X is a sulfonic acid residue, n is the same number as the sulfonyloxy group of the sulfonic acid residue, and represents an integer of 1 to 4. An alcohol metabolism promoter characterized by containing an acyloxyalkanoylcholine sulfonate derivative represented by the following as an active ingredient. (2) Claim 1 in which R^1 and R^2 are methyl groups.
Alcohol metabolism accelerator as described. (3) The alcohol metabolism promoter according to claim 1 or 2, wherein X is a monosulfonic acid residue or a disulfonic acid residue. (4) The acyloxyalkanoylcholine sulfonate derivative is bis(2-trimethylammonioethyl=α-
The alcohol metabolism accelerator according to claim 1, which is acetoxypropionate-naphthalene-1,5-disulfonate.