JP2002104984A - Medicinal composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medicinal composition containing an excellent effect for preventing and treating hangover, especially a composition for gastroenteropathy, a composition for preventing and treating the hangover, a composition for promoting the elimination of alcohol, an analgesic composition, and a composition for inhibiting hypoglycaemia caused by the intake of alcohol. SOLUTION: This medicinal composition is characterized by containing scutellariae radix or its extract, Phellodendri cortex or its extract, Coptic japonica or its extract, and rhizome of Zingiber officinale or its extract.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a pharmaceutical composition, particularly a composition for gastrointestinal diseases, a composition for preventing or treating hangover, a composition for promoting alcohol disappearance, a composition for analgesic, and blood glucose by alcohol intake. The present invention relates to a composition for suppressing a decrease in value.

[0002]

2. Description of the Related Art Numerous studies have been conducted on the cause of hangover, which is largely caused by excessive intake of alcohol. It is said that the cause is vomiting due to acetaldehyde, which is an ethanol metabolite, nausea, headache, palpitations, and a decrease in blood glucose level due to ethanol intake, but there are still many unknowns. Until now, various drugs have been known as drugs for preventing and treating hangover, but none of them have satisfactory effects.

[0003]

DISCLOSURE OF THE INVENTION The present invention relates to a pharmaceutical composition excellent in prevention and treatment of hangover, especially a composition for gastrointestinal diseases,
An object of the present invention is to provide a composition for preventing and treating hangover, a composition for promoting alcohol disappearance, a composition for analgesia, and a composition for suppressing a decrease in blood glucose level due to alcohol intake.

[0004]

The present invention has the following constitution. 1) A pharmaceutical composition comprising oak or its extract, oak or its extract, oak or its extract, and ginger or its extract. 2) The pharmaceutical composition as described in 1) above, further comprising animal gall. 3) The pharmaceutical composition according to the above 1) or 2), further comprising a carrot or an extract thereof. 4) The above-mentioned 1) to, characterized in that the composition is a composition for gastrointestinal diseases.
The pharmaceutical composition according to any of 3). 5) The pharmaceutical composition according to any one of 1) to 3) above, which is a composition for preventing or treating hangover. 6) The above 1) to above, which are characterized by being an analgesic composition.
The pharmaceutical composition according to any of 3). 7) The pharmaceutical composition according to any one of 1) to 3) above, which is a composition for suppressing a decrease in blood glucose level due to alcohol intake.

[0005] The pharmaceutical composition of the present invention (hereinafter, also referred to as the composition of the present invention) essentially contains pentagon, oak, spinach, and ginger, and preferably further contains animal gall,
Although it is a composition containing carrots, this composition is particularly suitable for physiological phenomena considered to be related to hangover.
As a result of finding that they have the following effects, they were found to be effective in preventing and treating gastrointestinal diseases and hangover, promoting alcohol disappearance, analgesia, and suppressing a decrease in blood glucose level due to alcohol intake. Analgesic effect (prevents or treats hangover headache, etc.) Blood glucose lowering inhibitory effect (alcohol intake lowers blood sugar and produces weakness, but suppresses blood sugar lowering) Ethanol metabolism promoting liver Inhibition of ADH and ALDH activity reduction in mice Anti-ulcer activity Enzyme activity in gastric mucosa, for example, suppression of MPO activity enhancement and SOD activity reduction In addition, the above-mentioned effects of the composition of the present invention are limited to those dependent on alcohol intake. Not done. For example, especially the anti-ulcer effect, the analgesic effect, etc. are not limited to those caused by alcohol intake.

Next, each component of the composition of the present invention will be described. Ougon (yellow gourd) is a root excluding the pericarp of Labiatae, and is known to have antibacterial, sedative, bile, and anti-inflammatory effects. Oak (huangkashi) is a bark of the periwinkle or other congener plants except for the pericarp, and is known to have antibacterial, astringent, anti-inflammatory, stomachic and diuretic effects. Spinach (Yellow) is a rhizome excluding the roots of Ranunculaceae or other congener plants, and is known to have antibacterial, anti-inflammatory, stomachic, and bile actions. Ginger is a rhizome of ginger, stomach, analgesic,
It is known to have an antiemetic effect.

[0007] Animal gall is the gallbladder of non-human animals (cows, bears, pigs, chickens, etc.), and is known to have an effect of inhibiting the absorption of alcohol. Bears are good but hard to obtain, and cows are commonly used. Usually, a dry viscous material or powder is generally used. Bile and components in bile contained in the gallbladder (bile acids:
Cholic acid, deoxycholic acid, chenodeoxycholic acid,
Ursodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, dehydrocholic acid, etc.) can be substituted. Colombo traversing the roots of Jateorhiza columba Miers (Menispermaceae) can be used in place of oak, oak and some or all of oak and / or oak contained in the composition of the present invention as a substitute for oak (this is It is known as oak and spinach.).

[0008] The present invention relates to a pharmaceutical composition containing the above-mentioned various crude drugs, wherein the crude drug can be freely adjusted in its form as required, and can be cut or crushed into small pieces or small pieces, Alternatively, it can be ground into a powder. Crude drug powder is commonly referred to as "crude powder", and for example, "showing powder" is referred to as "showing powder".

In the present invention, a crude drug extract refers to a liquid leached by adding a suitable leaching agent to a crude drug, or a liquid obtained by concentrating a leached solution, and specifically, “extract” and “tincture”.
And the like. For example, examples of the extract of "ouren" include "ouren extract" and "ourn tincture". Leaching agents include methanol,
Lower monohydric alcohols such as ethanol and n-butanol,
Ethylene glycol, propylene glycol, 1,3-
Lower polyhydric alcohols such as butylene glycol and glycerin; ethers such as diethyl ether; ketones such as acetone and ethyl methyl ketone; esters such as ethyl acetate; halogenoalkanes such as dichloromethane and chloroform; benzene and toluene; Examples include aromatic hydrocarbons and water. These leaching agents may be used alone or in combination of two or more, or may be used after being heated. The extract may be prepared by a known method (for example, a method described in the Japanese Pharmacopoeia).

[0010] Dried "extract" is also included in the extract of the present invention, and is usually referred to as "dry extract".
For example, a dried extract of "Ogon" is referred to as "Ogon dried extract". A known method may be used for producing the dry extract. In general, as long as a crude drug has the same base, the same effect can be obtained in any form.

The composition of the present invention can be administered orally or parenterally, but is preferably administered orally. Preparations for oral administration include liquid forms such as extracts, elixirs, syrups, tinctures, and limonade and solid forms such as capsules, granules, pills, powders, and tablets. Things can be mentioned. In the present invention, a solid preparation is preferred as the dosage form. The preparation containing the composition of the present invention can be prepared into various dosage forms by known preparation techniques, and an appropriate preparation additive can be added to the preparation. Specific examples of formulation additives include:
Examples include excipients, binders, disintegrants, suspending agents, preservatives, antioxidants, flavoring agents, and the like. Pharmaceutical additives need to be harmless to the living body such as the human body at the dosage of the preparation, and they do not have to hinder the effect of the active ingredient.

For example, excipients include lactose, corn starch, crystalline cellulose, etc., and binders include gum arabic powder, dextrin, carboxymethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, etc., and disintegrants Include corn starch, carboxymethylcellulose, carboxymethylcellulose calcium, crospovidone, etc., as suspending agents, sodium alginate, polyvinylpyrrolidone, etc., and as preservatives, ethyl paraoxybenzoate, butyl paraoxybenzoate, etc. Examples of the antioxidant include ascorbic acid and tocopherol, and examples of the flavoring agent include sucrose, honey, aspartame, stevia, dipotassium glycyrrhizinate, and the like.

The daily dosage of each crude drug of the composition of the present invention in terms of the crude drug is as follows.
Various selections can be made according to the symptoms. Ogun is usually 5
0 mg to 15 g and 100 mg to 2500 mg are preferred. Spinach is usually 25 mg to 10 g, 50 mg to
2500 mg is preferred. Orb is usually 25mg
10 to 10 g, 50 mg to 2500 mg are preferred. Colombo is usually 25mg-10g, 50mg-2500m
g is preferred. Ginger is usually 10 mg to 10 mg
g, 50 mg to 2500 mg are preferred. Usually, 5 mg to 1 g and 25 mg to 500 mg of animal bile are preferable.
Carrots are 50mg-15g, 100mg-5000
mg is preferred.

The composition of the present invention is not limited in its mixing ratio, but 0.5 to 2 parts by mass of urene and 0.5 to 2 parts by mass of oleum per 1 part by mass of ogon in terms of a crude drug.
2 parts by mass, 0.5 to 2 parts by mass of ginger, animal gall.
What mix | blends 3-1 mass parts and 0.3-2 mass parts of carrots is mentioned. Also, 0.7 to 1.5 parts by mass of orange, 0.7 to 1.5 parts by mass of oak, 0.7 to 1.5 parts by mass of ginger, and 0.7 parts by mass of animal gall with respect to 1 part by mass of orange as a crude drug. 0.3-0.8 parts by mass, carrot 0.4-
A composition in which 1.5 parts by mass is blended is preferable, and a composition blended in a ratio of 12: 12: 12: 12: 12: 5: 6 is particularly preferable. .

To take the composition of the present invention orally, 1
You only need to take it in 4 divided doses.
Before meals, between meals, after meals, before bedtime, and the like. The amount of administration (dose) can be appropriately increased or decreased depending on age, sex, body weight, and symptoms. The composition of the present invention can be used for overdrinking, barking (upset hangover / sickness), vomiting, loss of appetite, leaning, weak stomach, overeating, chest catch, heartburn, stomach / abdominal bloating due to indigestion, digestion It is effective in poor blood pressure, various pains, lowering of blood sugar level due to alcohol intake, and the like.

[0016]

The present invention will be more specifically described below with reference to the composition of the present invention and test examples thereof.

(Test Example 1) Analgesic activity (acetic acid writhing method) Method The group consisted of 10 to 12 male ddy mice fasted overnight, and 0.2 ml of the test drug consisting of the following crude drugs and compounding ratios: Per animal. In addition, 0.2 ml / animal of purified water was administered to the control group (the same applies hereinafter). Thirty minutes later, a 0.7% acetic acid aqueous solution was intraperitoneally administered at 0.2 ml / animal, and the number of writhings occurring 15 minutes after intraperitoneal administration was measured as an index of pain. The inhibition rate was determined by the following equation and is shown in Table 1. Test drug Formulation A (composition of the present invention): ginger, yellow candy, yellow liquor, yellow orchid,
Beef bile (1: 1: 1: 1: 0.5) Formulation B (comparative composition): Yellow bean, Huangbashi, Oren, Beef bile (1: 1: 1: 0.5) Formulation C: Ginger Among the test drugs, Oren and Huangbai used the Oren extract (commercially available) and Huangkashi extract (commercially available), and yellow gourd used the dried extract of Huangyuan (commercially available). Dosage 100 in Table 1
(Mg / kg) means, for example, in the case of Formulation A, 100 g (100 g / kg) of ginger and 100 g
/ Kg), Hakubashi 100 (mg / kg), Huanglian 100 (m
g / kg) and 50 g / kg of bovine bile (mg / kg) was administered, and the same applies to this test example and thereafter. Inhibition rate (%) = ((Rising number of control group−Rising number of test drug administration group) / Rising number of control group) × 10
0

[0018]

【table 1】

Results As is clear from the above table, ginger showed an analgesic effect depending on the dose. However, the formulation A according to the present invention used ginger and other herbal component formulation B in combination, so that ginger in the formulation was not used. Showed an analgesic effect higher than that of Formula C even when the amount of the compound was smaller than that of Formula C.

(Test Example 2) Action on blood ethanol concentration after ethanol administration (alcohol elimination promoting action)-Method: One group of 10-12 male ddy mice fasted overnight was composed of the following crude drugs and combinations shown below. The test drug at a ratio of 0.2 ml / animal was orally administered. Thirty minutes after the administration, 0.4 ml / animal of 30% ethanol was orally administered. 1, 3, and 6 hours after ethanol administration, using a 500 U heparin-containing syringe,
0.7 ml of blood was collected from the animals. Cold 1mol / l in 0.4ml of collected blood
-0.4 ml of perchloric acid was added and mixed, left under ice-cooling for 15 minutes, and then centrifuged. The supernatant was separated and the ethanol concentration was measured. That is, 0.2 mol / l-curicin buffer was added to 0.1 ml of the supernatant.
(pH 10.6) 3 ml, and NAD (5 mg / ml) 0.05 ml
After standing at 5 ° C. for 5 minutes, the absorbance (E ₀ ) at 340 nm was measured. Thereafter, 0.05 ml of ADH (500 U / ml) was added, and after 10 minutes, the absorbance (E ₁ ) at 340 nm was measured again, and the difference in absorbance (E ₁ −E ₀ ) was determined. The ethanol concentration was determined. The data for 6 hours after ethanol administration are shown in Table 2.

Test Drugs Formulation A-1: Ginger Formulation A-2 (comparative composition): Gongo, Huangbashi, Huangren (1:
1: 1) Formulation A-3: Beef bile Formulation A-4 (composition of the present invention): Ginger, yellow garlic, yellow oak, orchid (1: 1: 1: 1) Formulation S-1 (composition of the present invention) ): Ginger, yellow beans, yellow croaker, yellow orchid, beef bile (1: 1: 1: 1: 0.5) result

[0022]

[Table 2]

From the above table, it can be seen that Formulations A-4 and S-1 according to the present invention, in which ginger is mixed with yellow sesame, yellow croaker, and yellow ren, have the effects of eliminating ginger from blood in Formula A-2 which does not contain ginger. It was shown to be higher. In addition, it has been found that ginger has a new alcohol-eliminating effect, and that the effect is enhanced when used in combination with Formulation A-2.

(Test Example 3) Action on blood glucose level after administration of ethanol. Method In the same manner as described above, the following crude drugs and test drugs having the following compounding ratios were orally administered, and collected 6 hours after administration of ethanol. 0.3 ml of the collected blood was centrifuged, and the resulting supernatant 2
0.2 ml of distilled water was added to 0 μl to mix and dilute. 0.025
Measurement kit using glucose oxidase per ml
The blood glucose level was measured using (glucose measurement test-B Wako). Table 3 shows the results. Test drug Formulation A: Ginger Formulation B (comparative composition): Yellow Gourd, Yellow Bamboo, Yellow Oren (1: 1:
1) Formulation C: beef bile Formulation D (composition of the present invention): ginger, yellow lentils, yellow oak, orchid (1: 1: 1: 1) Formula E (comparative composition): yellow lentils, yellow ash, yellow Ren, Gyu-bile (1: 1: 1: 0.5) Formulation F (the composition of the present invention): ginger, yellow candy, yellow mulberry, yellow ren,
Ushibile (1: 1: 1: 1: 0.5) Results

[0025]

[Table 3]

As is apparent from the above table, alcohol consumption has an effect of lowering blood sugar level, and the prescription B of the comparative composition promotes the lowering effect. Formulations D and F according to the formula (1) showed an excellent inhibitory effect on blood glucose level due to alcohol intake.

(Test Example 4) Inhibitory effect of hepatic drug-metabolizing enzyme (alcohol-metabolizing enzyme) activity reduction after administration of ethanol. Method: A group of 10-12 male ddy mice fasted overnight was used in (Test Example 2). Thirty minutes after the administration of the test drug having the indicated composition crude drug and compounding ratio, 30% ethanol was orally administered at a concentration of 0.4 ml / animal. One hour after the administration of ethanol, the liver was removed and cold water was added to homogenate. Homogenate solution is 0 ℃, 10,000
The mixture was centrifuged at 00 rpm for 30 minutes, and the supernatant was separated and used as an enzyme solution. After adding a phosphate buffer (pH 8.3) containing 25 mg / ml NAD to this enzyme solution, 10 μl of 10% ethanol or 10% acetaldehyde was added, and the time-dependent change in absorbance at 340 nm was measured using a spectrophotometer. . The enzymatic activity was expressed as a specific activity per 1 mg of protein, where the change in absorbance per minute was 0.001 as 1 U. The results are shown in Table 4. ·result

[0028]

[Table 4]

From the above table, it can be seen that the composition of the present invention is effective for ADH
In addition, it can be seen that it suppresses a decrease in ALDH activity and is effective in preventing and treating hangover.

(Test Example 5) Anti-ulcer action (protective action on gastric mucosa) and enzyme
OD activity decrease inhibitory action Six weeks old birth ddy male mice were fasted in a wire mesh cage for 18 hours, and then orally administered a test drug having the composition ratio and composition shown in (Test Example 2) (n = 19). ). After study drug administration
In 30 minutes, 0.2 ml / animal of 60% ethanol containing 150 mM hydrochloric acid was orally administered. Ninety minutes after the ethanol administration, the animals were sacrificed by cervical dislocation, the stomach was removed and the stomach was removed. The removed stomach was divided into two groups. One group was injected with 1 ml of 10% formalin and fixed for 30 minutes.
An incision was made in the greater bay and the ulcers that developed in the fundus were measured (n =
9). For the stomach of the other group, the bottom of the stomach was sliced and then
1 ml was added and homogenized, centrifuged at 10,000 rpm for 30 minutes at 0 ° C., and the supernatant was fractionated to obtain myeloperoxdase (hereinafter referred to as MPO) and superoxide disumutase (hereinafter referred to as SO).
D) Activity was measured (n = 10). The enzyme activity was expressed as a specific activity per mg of protein. MPO activity was determined by the method of Suzuki et al. (An
al. Biochem. 132, 345-352, 1983), 1.6 mM tetramethylbenzoic acid, 15 mM aqueous hydrogen peroxide, 80 mM phosphate buffer (pH
5.4), 5 μl of enzyme solution in a solution consisting of 8% methylformamide and 40% PBS
Was added and incubated at 37 ° C. for 20 minutes, and then the reaction was stopped by adding 200 mM acetic acid (pH 3.0). The absorbance at 650 nm of this solution was measured using a microplate reader. The enzymatic activity was expressed as the specific activity per 1 mg of protein, where the change in absorbance per minute was 0.001 as 1 U.
The SOD activity was determined by the method of Oyanagi (Anal. Biochem. 142, 290-29
6, 1984), 0.25 mM hydroxylamine hydrochloride, 0.25 mM
After adding 10 μl of the enzyme solution to 20 mM phosphate buffer (pH 8.2) containing mM xanthine and 0.025 mM EDTA, 100 μl of xanthine oxidase (25 U / ml) is added, and the mixture is reacted at 37 ° C. for 45 minutes. The reaction was stopped by adding 100 μl of an acetic acid solution consisting of, followed by measuring the absorbance at 570 nm using a microplate reader. For the enzyme activity, a calibration curve was prepared from a bovine serum SOD standard, and the specific activity per 1 mg of protein was determined therefrom. In addition, the protein amount was measured by the buret method. The results are shown in Tables 5 to 7. ·result

[0031]

[Table 5]

[0032]

[Table 6]

[0033]

[Table 7]

When hydrochloric acid-ethanol was administered, an ulcer with hemorrhage occurred in the glandular stomach in the control. However, those administered with the formulation S-1 of the composition of the present invention exhibited excellent anti-ulcer action. In addition, the composition of the present invention has M
It has been found that the composition of the present invention has an effect of suppressing the enhancement of PO activity and also has an effect of suppressing the effect of reducing the SOD activity found in the control, and the composition of the present invention is effective in protecting the gastric mucosa. It has been found.

(Preparation Example) A pill containing the composition of the present invention containing the following components as main components was prepared. (Daily dose (in 9 pills)) Ogon dried extract 50 mg (300 mg as crude drug) Oubak dried extract 50 mg (300 mg as crude drug) Ouren extract 50 mg (300 mg as crude drug) Carrot powder 150 mg Ginger powder 300 mg Ursodesoxychol Acid 45mg Animal bile (cow bile) 125mg

(Test Example 6) Administration test Twenty healthy adult men were divided into two groups of 10 subjects each. One group was asked to take 3 pills of the above formulation at 7:00 pm, and 20 minutes after taking the same amount of alcohol (sake, beer,
(Whiskey) and dinner. After drinking 30
At the same time, 3 tablets of the above preparation were taken again, the patient was put to sleep at 10 pm, and the subjective symptoms at 7 am the next morning were examined. When the above-mentioned preparations were not taken, hangover symptoms such as headache and ill feeling remained, whereas when the above-mentioned preparations were taken, it was recognized by all 10 subjects that there were few hangover symptoms. Examination of the symptoms revealed it. The other group had dinner at 7:20 pm with an amount of alcohol (sake, beer, whiskey) equivalent to 5 go sakes, and went to bed at 10 pm. At 7:00 am the next morning, subjective symptoms were examined, and nine patients who had hangover symptoms such as headache and feeling unwell were given three tablets of the above preparation.
Examination of subjective symptoms revealed that when the above-mentioned preparation was taken, the recovery of the hangover symptoms was greater than when the above-mentioned preparation was not taken.

[0037]

Industrial Applicability The present invention, which contains a specific crude drug component, is effective in improving gastrointestinal illness, preventing and treating hangover, promoting alcohol disappearance, analgesia, and suppressing a decrease in blood glucose level due to alcohol intake. .

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 35/37 A61K 35/37 A61P 1/00 A61P 1/00 1/04 1/04 3/08 3 / 08 25/04 25/04 39/02 39/02 (72) Inventor Hiroya Shimizu 3-14-10 Nihonbashi, Chuo-ku, Tokyo F-term (in reference) 4C087 AA01 AA02 BB49 CA06 ZA08 ZA69 ZC35 ZC37 ZC75 4C088 AB32 AB38 AB40 AB62 AB81 AC05 AC11 AC13 BA08 CA03 MA07 ZA08 ZA69 ZC35 ZC37 ZC75

Claims (7)

[Claims] 1. A pharmaceutical composition characterized by containing oak or its extract, oak or its extract, oak or its extract, and ginger or its extract. 2. The pharmaceutical composition according to claim 1, further comprising animal gall. 3. The pharmaceutical composition according to claim 1, further comprising a carrot or an extract thereof. 4. The pharmaceutical composition according to claim 1, which is a composition for gastrointestinal diseases. 5. The pharmaceutical composition according to claim 1, which is a composition for preventing and treating hangover. 6. The pharmaceutical composition according to claim 1, which is an analgesic composition. 7. The pharmaceutical composition according to any one of claims 1 to 3, which is a composition for suppressing a decrease in blood glucose level due to alcohol intake.