JPH11222438A - Absorption inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an alcohol absorption inhibitor having actions of suppressing the rise in alcohol level in blood after ingesting the alcohol by including one or more kinds selected from a specific crude drug powder or extract and soyasaponins. SOLUTION: This alcohol absorption inhibitor is obtained by including at least one kind selected from a crude drug powder or extract selected from Evodiae Fructus and Lycii Fructus and soyasaponins as an active ingredient. A stomachic selected from a crude drug powder or extract of Panacis Rhizoma and Evoidae Fructus and carinitine chloride and a crude drug powder or extract of Platycodi Radix and Lycii Fructus and soyasaponins which are not the stomachic are found to have alcohol absorption inhibiting effects. The crude drug powder includes a fine powdery shape, a granular shape, etc., and the extract includes an aqueous extract, a fluide extract, a tincture, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an alcohol absorption inhibitor comprising, as an active ingredient, any one or two of a crude drug powder or extract selected from Goshuyu and Kukushi, and soybean saponin. The present inventors have found that a gastroenteric agent selected from the ginseng and goshyu herbal medicine powder or extract, and carnitine chloride, has an alcohol absorption inhibitory effect.
It was also found that the same effect was found in powdered or extracted herbal powders and extracts of Kukiyou and Kokushi, and soybean saponin. In the following, first, ginseng, goshyu, and carnitine chloride, which are useful as a stomachic, will be described first, followed by goldfish, kukushi, and soybean saponin. The preparation according to the present invention containing carrot, ginseng or carnitine chloride, in addition to the action of improving gastrointestinal function, suppresses the absorption of alcohol in the digestive tract, thereby preventing an increase in blood alcohol concentration and preventing the adverse effects of drinking. It protects the living body.

[0002]

2. Description of the Related Art Ethanol taken orally as an alcoholic beverage is absorbed through the gastrointestinal tract, mainly the stomach, duodenum and small intestine, and then transported to the whole body through blood. 90% of the absorbed alcohol is oxidized by an enzymatic reaction in the liver and is first metabolized to acetaldehyde, then to acetic acid, and finally to water and carbon dioxide. It is thought that the expression of so-called dairy intoxication is complicatedly related to the direct action of alcohol, as well as metabolites such as acetaldehyde, imbalance in electrolytes, and biogenic amines.
Among them, acetaldehyde having a strong pharmacological action is said to be a cause of sickness, and various trapping agents, toxicity reducing agents, and metabolism promoting agents for acetaldehyde have been reported. In addition, various stomach-combining agents have been conventionally used for improving gastrointestinal discomfort due to sickness and hangover.

[0003]

SUMMARY OF THE INVENTION In order to drink alcoholic beverages healthily, the present inventors have reduced or neutralized any adverse effects on the living body due to the toxicity of alcohol itself and its metabolite, acetaldehyde. Therefore, it was considered that a drug that inhibits an increase in blood alcohol concentration by inhibiting the absorption of alcohol from the digestive tract would be effective. Also, it is well known that alcohol and alcohol metabolism adversely affect the metabolism of various nutrients and vitamins in the liver (see Reference 1, listed at the end of this specification,
However, in practice, fluctuations in dietary conditions can be a major factor in worsening nutritional conditions (Reference 4). That is,
Alcohol overdose leads to irregular dietary intake, reduced appetite, reduced dietary intake, and upper digestive tract disorders caused by alcohol, resulting in indigestion,
It is thought to lead to nutrient and vitamin deficiencies. Therefore, it is also effective to improve the gastrointestinal discomfort by taking the stomachic after taking alcohol, but it is also very effective to take the stomachic before taking alcohol to improve the nutritional intake conditions.

[0004] However, some stomach medicines have no effect on alcohol absorption even if administered before ingesting alcohol, and conversely, some stomach medicines promote alcohol absorption and enhance alcohol toxicity. Taking it is not very effective in protecting against alcohol toxicity. The present inventor paid attention to this point, and searched for various components capable of suppressing an increase in blood alcohol concentration among stomachic components in order to obtain a drug capable of protecting the living body from both gastrointestinal function and alcohol toxicity. .

[0005]

As a result, among the components of the stomach medicine, the crude drug powder or extract of ginseng and goshyu and carnitine chloride have the effect of suppressing an increase in blood alcohol concentration after alcohol intake. ,
In other words, it was clarified that suppressing the absorption of alcohol from the digestive tract reduces the amount of alcohol transferred to the blood. Therefore, if these stomachic components are administered,
It is thought that the living body can be very effectively protected from the toxicity of alcohol and its metabolites at the same time as the regulation of the gastrointestinal tract function by the stomachic effect. As used herein, the term "herbal powder or extract" refers to the normal form in which the herbal medicine is used for its intended purpose, and thus should be understood to refer to the specific form literally. No. That is, the crude drug powder includes, for example, those processed into fine granules and granules, or so-called “raw” and “chopped”, and the extracts also include aqueous extracts, fluid extracts, tinctures, and the like. However, the present invention is not limited to these.

[0006] Carnitine chloride, which is the active ingredient of the present invention, can be easily obtained from a commercial drug, and Chixet ginseng and Goshuyu can be obtained either as powder or extract as crude drug materials. Carnitine chloride is a gastrointestinal function regulator,
Gixetin ginseng and goshyu are stomachic herbal medicines, but both have gastrointestinal function-improving activity, and are used in gastrointestinal pills for various purposes such as antacid, stomachic, digestion, intestinal control and antidiarrheal. It is. Amino acids such as glycine and alanine, citric acid, organic acids such as malic acid, inorganic salts such as sodium chloride and potassium chloride, vitamins, etc.
Other crude drug powders and extracts, fragrances and the like can be blended. In addition, all oral administration forms such as powders, granules, tablets, capsules and the like can be used as the form of ingestion.

[0007] Even if the same amount of alcohol is consumed, the absorption and metabolism rate varies greatly between individuals due to differences in body weight, constitution, and the like, and the effective amount of the active ingredient of the present invention cannot be clearly defined. A sufficient alcohol absorption inhibitory effect can be expected within the effective dose range when used for the purpose of use. That is, when only one kind is used, preferably, the daily dose is 6 to 600 mg for carnitine chloride, 0.6 to 6 g for carrot extract, 0.3 to 3 g for powder, and 0.3 to 3 g for powder. Is 0.3 ~ 3 in case of extract
g or powder, 0.1 to 1 g is a guide. When two or more kinds are combined, the amount is appropriately reduced. Regarding the time of taking, it is effective to take it before or at the same time as alcohol intake to prevent sickness and hangover, but it is also possible to take it after alcohol intake to reduce sickness and hangover. As described above, the present inventors have found that, although they are not stomach medicines, crude powders of kyoto and kokushi and soybean saponin also have an alcohol absorption inhibitory effect. These are all commercially available, and their daily dose is 0.01 to 5 g.
Is within the range. Hereinafter, the present invention will be described in more detail with reference to Examples and Preparation Examples.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Experimental Example 1 (1) Experimental animal After pre-breeding male Wistar rats for 1 week, they weighed 15
Used at 0-180 g. The animals were fasted overnight before the experiment, and fasted during the experiment.

(2) Experimental method Rats were administered with alcohol alone (distilled water) (control group 1), alcohol alone (1 w / v% CMC) (control group 2), carnitine chloride administration group, and thixet ginseng administration. The group was divided into 5 groups, i.e., Goshuyu administration group. As the alcohol, a solution prepared by diluting ethyl alcohol to 20 v / v% with distilled water was orally administered to all cases at a volume of 10 ml / kg, and the test drug was orally administered 1 hour before the alcohol administration as follows. That is, carnitine chloride was prepared from a 20% w / v solution in distilled water, and the ginseng extract powder was 25% w / v.
% And Goshuyu powder were administered at a volume of 10 ml / kg prepared from a 5% w / v solution in a 1% aqueous CMC (sodium carboxymethylcellulose) solution. Control group 1 was administered distilled water in place of the test drug, and control group 2 was administered a 1% CMC aqueous solution at a dose of 10 mg / kg. At 0.5, 1, 2, 3, and 4 hours after the alcohol administration, the abdomen was opened under ether anesthesia in 5 cases per group, and blood was collected from the abdominal vena cava into a heparin sodium-coated vacuum blood collection tube. Next, 0.5 ml of the collected blood was added to a centrifuge tube previously filled with 4 ml of 0.33N perchloric acid solution and cooled with ice, stirred vigorously, and centrifuged at 4 ° C. at 3,000 rpm for 5 minutes. The supernatant was collected. Use this supernatant for blood alcohol concentration.
Blood alcohol UV test "B" based on enzyme method (Reference 5)
MY "(Boehringer Mannheim Yamanouchi).

(3) Experimental Results FIG. 1 shows the time course of blood alcohol concentration in the control group 1 and the carnitine chloride-administered group. That is, control group 1
In the first hour of alcohol administration, the blood concentration was 1.5 mg / ml.
, And gradually decreased thereafter, and almost disappeared by 4 hours. On the other hand, in the carnitine chloride administration group, the control group 1
, And a blood concentration of 0.2 to 0.4.
The change was almost flat at mg / ml. In particular, a significant inhibitory effect of 80% or more (P <0.001) was exhibited until the second hour of administration, and a significant inhibitory effect of 40% even at the third hour of administration.
(P <0.05). For comparison, AUC (0-4) (area under the blood concentration curve from 0 to 4 hours) was calculated based on the trapezoidal rule.
・ H / ml, 0.99mg ・ h / ml in carnitine chloride administration group
And the suppression rate with respect to the control group 1 was 71%. Therefore, it was shown that the administration of carnitine chloride inhibited the absorption of alcohol and reduced the amount of the alcohol transferred to the blood, and the blood alcohol concentration was suppressed to a low level.

The time course of the blood alcohol concentration in the control group 2, the ginseng ginseng administration group and the goshuyu administration group is shown in the second section.
Shown in the figure. First, in the control group 2, the blood concentration reached a maximum at 1.2 mg / ml at 1 hour after alcohol administration, and gradually decreased thereafter, and almost disappeared at 4 hours. In the ginseng ginseng administration group, the transition was similar to that of the control group 2, but the concentration was lower than that of the control group 2 until 2 hours after the administration.
That is, at the 0.5 hour, the inhibitory effect was 42% (P <0.10), and at the first hour of the peak, the inhibitory effect was 13%.
As compared with (0-4), the suppression rate was 17%. On the other hand, in the Goshuyu-administered group, the peak time was delayed by one hour, peaked at the second hour, and then gradually decreased similarly to the control group 2. The blood concentration suppression rate was 41% at 0.5 hour (P <0.05), 1
It showed 24% (P <0.10) at the hour, and AUC (0-4)
Was 14%. From the above, it was shown that, although both ginseng and goshuyu were slightly less effective at this dose, similar to carnitine chloride, the blood alcohol concentration was suppressed to a low level by inhibiting alcohol absorption from the gastrointestinal tract. Was. The same experiment as described above was also performed for Kikyo, Kokushi, and soybean saponins. The outline is shown below.

Experimental method Soybean saponin was 10 W / V%, and Kikyo flow extract was 40 W / V%.
/ V%, kokushi flow extract was prepared by preparing a 20 W / V% solution in a 1% CMC aqueous solution at a volume of 10 ml / kg.
Control group 3 received a 1% aqueous CMC solution at a volume of 10 ml / kg. Experimental Results FIG. 5 shows the time course of the blood alcohol concentration in the control group 3, the soybean saponin administration group, the fennel administration group, and the kokushi administration group. Soybean saponin and kukushi decreased the blood alcohol level at 0.5 and 1 hour after alcohol administration, and Kikyo obviously decreased the blood level at 0.5 to 3 hours.

Experimental Example 2 (1) Experimental Animal The same rat as that used in Experimental Example 1 was used for the experiment. (2) Experimental method In this experiment, the dose response of alcohol absorption inhibitory effect of carnitine chloride, a gastrointestinal function-modifying agent, and thixet ginseng among stomachic crude drugs was examined. Rats with alcohol alone
(Distilled water) administration group (control group 1), alcohol alone (1 w / v%
CMC) administration group (control group 2), carnitine chloride (1.0, 1.
5, 2.0, 4.0 g / kg) administration group and ginseng
(2.5, 5.0, 10.0 g / kg)
There were 5 cases in the group. Alcohol is 20v of ethyl alcohol
A 10% v / v diluted aqueous solution was orally administered to all cases, and the test drug was orally administered 1 hour before alcohol administration as follows. That is, carnitine chloride is 10, 15, 2
A 0, 40 w / v% aqueous solution is administered at a volume of 10 ml / kg, and the ginseng extract powder is prepared at 25, 50, 100 w / v% with a 1% CMC aqueous solution at 10 ml / kg.
Was administered. Control group 1 rats were given distilled water instead of test drug, and control group 2 rats were given 10 ml of 1% CMC aqueous solution.
/ Kg dose. One hour after the alcohol administration, blood was collected from each of the administration groups in the same manner as in Experiment 1, and the blood alcohol concentration was measured.

(3) Experimental Results The following Table 1 shows the blood concentrations of carnitine chloride and ginseng carrots 1 hour after alcohol administration and the inhibition rates for the respective control groups. FIG. 3 shows the dose-response curves.

[0015]

[Table 1]

That is, the data in Table 1 were plotted with the log dose on the horizontal axis and the inhibition rate on the vertical axis. As a result, it was clarified that both carnitine chloride and carrot ginseng have a dose-dependent blood alcohol concentration lowering effect, that is, an alcohol absorption suppressing effect. Therefore, the time course of the blood alcohol concentration shown in Experimental Example 1 shows that the blood concentration in the first hour at the peak is dose-dependent. It is expected that a curve will be obtained. Further, the ED50 can be obtained by the linear regression method.
As shown in the above, carnitine chloride was 1.84 g / kg, and ginseng extract was 3.83 g / kg.

Experimental Example 3 (1) Experimental Animal The same rat as that used in Experimental Example 1 was used for the experiment. (2) Experimental method Rats were divided into two groups, a group administered with alcohol alone (control group) and a group administered with carnitine chloride. The former was 30 cases and the latter was 20 cases. As the alcohol, a 20 v / v% diluted aqueous solution of ethyl alcohol was orally administered to all cases in a volume of 10 ml / kg. One hour later, the carnitine chloride-administered group received a 25 w / v% carnitine chloride aqueous solution, and the control group received 10 ml of distilled water.
/ Kg orally. In the control group, at 0.5, 1, 1.5, 2, 3, and 4 hours after alcohol administration, and in the test drug administration group at 1.5, 2, 3, 4, and 5 hours, five animals each had Experimental Example 1. Blood was collected in the same manner and blood alcohol concentration was measured.

(3) Experimental results As shown in FIG. 4, the carnitine chloride-administered group showed 15, 19 and 37% significant (P <0.05) 1.5, 2, and 3 hours later than the control group. ) A decrease was observed. Therefore, it was shown that, even when the alcohol absorption inhibitor of the present invention was used after administration of alcohol, the amount of alcohol transferred to the blood was reduced by suppressing the subsequent absorption of alcohol. Formulation Example 1 [Solution] Composition Carnitine chloride 200 mg Chixet ginseng extract 50 mg Goshuyu powder 100 mg Sucrose 1000 mg Citric acid 70 mg Flavor 0.03 ml Combine the above ingredients, add water to make the total amount 30 ml, and take this as a single dose.

[0019] After mixing in the above ratio, a small amount of water is added, and the mixture is combined, granulated, dried and divided by a kneading machine to make a single dose.

[0020] Mix and tablet in the above proportions. In the case of a capsule, this is pulverized, mixed with magnesium stearate, and filled with a capsule filling machine. One dose is 2 tablets or 2 capsules. Literature 1. Rosen, HM, Yosimura, N., et al .: Plasma
amino patterns in hepatic encephalopathy of differ
ing etiology. Gastroenterlogy, 72: 483-48
7, 1977.2. Shaw, S., Lieber, CS: Plasma amino acid
abnormalities in the alcohlic: respective role of
alcohl, nutrition and liver injury. Gstroenterolo
gy, 74: 677-682, 1978. 3. Banks, WL Jr., Kline, ES, Higgns, E.
S .: Hepatic composition and metabolism after eth
anol consumpsion in rats fed liquid purifieddiet
s. J. Nutr., 100: 581-594, 1970. 4. Mφrland, j., Flengsrud, R., et al .: Hepatic
amino acid levels inrats after long-term ethanol
feeding. Biochem Pharmacol., 28: 423-42.
7, 1978. 5.5. Bucher, Th., And H. Redetzki, Klin. Wschr.
29: 615, 1951.

[Brief description of the drawings]

FIG. 1 is a graph showing a change in blood alcohol concentration due to administration of carnitine chloride.

FIG. 2 is a graph showing a change in blood alcohol concentration due to administration of Chixin ginseng or Goshuyu.

FIG. 3 is a graph showing dose response curves of carnitine chloride and ginseng.

FIG. 4 is a graph showing changes in blood alcohol concentration by carnitine chloride administration.

FIG. 5 is a graph showing changes in blood alcohol concentration due to administration of Kikyo, Kokushi or soybean saponin.

──────────────────────────────────────────────────続 き Continued on front page (51) Int.Cl. ⁶ Identification code FI A61K 31/205 A61K 31/205

Claims (1)

[Claims] 1. An alcohol absorption inhibitor comprising, as an active ingredient, any one or two of a crude drug powder or extract selected from Goshuyu and Kukushi, and soybean saponin.