JP2003026584A - Therapeutic agent for liver disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a natural product-based therapeutic agent for liver diseases usable in the fields of foods, medicines, cosmetics, etc. SOLUTION: This therapeutic agent for the liver diseases is characterized as comprising an extract from plants of the genus Ampelopsis of the family Vitaceae, especially one or more species of the plants of the genus Ampelopsis selected from Ampelopsis grossedentata, Ampelopsis megalophylla and Ampelopsis cantoniensis as an active ingredient. Furthermore, the therapeutic agent for the liver diseases is characterized as comprising dihydroflavonols, especially ampelopsin as the active ingredient.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent for liver diseases having a remarkable inhibitory effect on or amelioration of liver function, and in particular, a natural product liver usable in the fields of food and drink, pharmaceuticals, cosmetics and the like. The present invention relates to a disease therapeutic agent.

[0002]

2. Description of the Related Art The liver plays a central role in sugar metabolism, protein metabolism, lipid metabolism, drug metabolism, detoxification metabolism, etc. in the living body, but viruses, drugs, alcohol, malnutrition, hepatic circulation system disorders, etc. It is damaged by various factors and causes liver diseases such as acute hepatitis, chronic hepatitis, fatty liver, jaundice and cirrhosis.

To date, only a few other malotilates have been clinically recognized and used as therapeutic agents for these liver diseases. In addition, even antiviral agents such as interferon have not been able to reliably eliminate hepatitis virus. Furthermore, no apparently effective therapeutic agent for liver diseases including rest, fluid therapy, drug therapy with steroids, immunostimulants and the like has been found.

For liver diseases, especially chronic liver diseases, at present, no satisfactory therapeutic agent has been found, and in particular, antiviral agents, steroid agents, immunostimulants, etc. However, there is a problem in that the drug treatment by the drug may cause serious side effects.

[0005]

SUMMARY OF THE INVENTION Under such circumstances, it is an object of the present invention to solve various problems in the prior art and achieve the following objects. That is, the present invention has a remarkable inhibitory effect on liver function reduction or improvement, is easy to use, excellent in safety, especially in the field of food and drink, pharmaceuticals, cosmetics, etc., can be suitably used natural product system It is intended to provide a therapeutic agent for liver diseases.

[0006]

In view of the above-mentioned problems, the present inventor has conducted earnest studies for the purpose of developing a more effective and safer therapeutic agent for liver disease, and as a result, the vine family Ampelops
Extracts of plants belonging to the is genus (particularly Fujicha
grossedentata), large leaf vine (Amp
Elopsis megaloylla) and Cantonese vines (Ampelopsis cantoniens)
The inventors of the present invention have found that an extract of is)) or dihydroflavonols (particularly ampelopsin) has a remarkable inhibitory effect on the deterioration or improvement of liver function, and have completed the present invention.

That is, the present invention provides the following therapeutic agent for liver diseases in order to solve the above-mentioned problems.

The invention of claim 1 is a therapeutic agent for liver diseases, which comprises an extract of a plant of the genus Ampelopsis of the family Vaceae as an active ingredient.

[0009] The invention of claim 2 is Fujicha (Ampelop)
sis grossedentata), large leaf vine (Ampelopsis megalophylla)
And Cantonese Grape (Ampelopsis canton)
The hepatic disease therapeutic agent according to claim 1, which comprises an extract obtained by extracting an Ampelopsis genus plant selected from (iensis) with water, a hydrophilic organic solvent or a mixed solvent thereof as an active ingredient.

A third aspect of the present invention is a therapeutic agent for liver diseases, which comprises at least one dihydroflavonol represented by the following general formula (1) as an active ingredient.

[0011]

[Chemical 2] (However, in the formula, R ^{1 to} R ⁵ each independently represent a hydrogen atom or a hydroxyl group.)

The invention according to claim 4 is the therapeutic agent for liver diseases according to claim 3, wherein the dihydroflavonol is an ampelopsin in which R ^{1 to} R ⁵ are all hydroxyl groups in the above general formula (1). .

In the invention of claim 5, the dihydroflavonols are Fuji tea (Ampelopsis glosseden).
tata), large leaf vine (Ampelopsis me)
galophylla), Cantonese snake grape (Ampelop)
sis cantoniensis), kenponashi (H
ovenia dulcis), Salix officinalis (Sal
ix sachalinensis), Japanese white pine (P
inus controller), Erythrophl
eum africanum and wig (Cercid
5. An isolated and purified product obtained from an extract of a plant selected from (iphyllum japonicum).
It is the therapeutic agent for liver disease described.

The invention of claim 6 is used for the prevention or treatment of acute or chronic viral hepatitis, acute or chronic drug-induced hepatitis or fulminant hepatitis.
The therapeutic agent for liver diseases according to the above item.

Among the plants belonging to the genus Ampelopsis of the family Vineaceae, the scientific name (Ampelopsis gros)
sedentata (Hand.-Mazz.) W.S.
T. Wang (Fuji tea) is known, and this Fuji tea is
It is a perennial vine plant that grows naturally in a wide area from central to southern China, and has been cultivated in Taiwan.In China, its leaves have been used as tea since ancient times, and it has been used for the treatment of colds and sore throats. It is a highly safe plant that has been used as a medicine.

On the other hand, as dihydroflavonols,
Ampelopsin and myricetin have been reported as the active ingredients of Fuji tea extract (Natural Product).
tResearch and Development
t, 9, 41-43 (1997)), but amperopsin is a large vine other than Fujicha (Ampelopsisme)
galophylla), Cantonese snake grape (Ampelop)
other Amp such as sis cantoniensis)
It has also been isolated from plants of the genus elopsis,
Lopsis plants, as well as Kemponashi (Hovenia)
dulcis), Salix sac
halinensis), Japanese white pine (Pinus c)
ontorta), Erythrophleum af
ricanum, wig (Cercidiphyllu)
m. japonicum) etc.,
May be widely present in the plant kingdom.

However, the pharmacological action of ampelopsin has not been clarified, and the wisteria tea extract has an action of eliminating active oxygen and an action of inhibiting platelet aggregation (Japanese Patent Laid-Open No. 2001-2001).
It is known that the plant of the genus Ampelopsis and ampelopsin have a therapeutic effect on liver diseases, which is a new finding of the present inventor. .

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in more detail below. As a first aspect, the therapeutic agent for liver diseases of the present invention comprises Ampelopsis of the family Vaceae.
It contains an extract of a genus plant as an active ingredient.

Ampelopsis (Ampel)
Examples of plants belonging to the genus Opsis include, for example, Fuji tea (Ampe).
lopsis grossedentata), Ampelopsis megalophyll
a) and Cantonese vine (Ampelopsis cant)
one or two or more kinds selected from among the (onensis) are preferably used. Of these, Fujicha is preferred.

The therapeutic agent for liver diseases of the present invention is prepared by using the plant of the genus Ampelopsis as a raw material for extraction and adding it to water or a hydrophilic organic solvent or a mixed solvent thereof at room temperature to a temperature not higher than the boiling point of the solvent. It can be obtained by extraction using any device.

The water that can be used as the extraction solvent includes pure water, tap water, well water, mineral water, mineral water, hot spring water, spring water, fresh water and the like, as well as those that have been subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present invention also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline and the like.

Examples of the hydrophilic organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone;
Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as 3-butylene glycol, propylene glycol, isopropylene glycol, and glycerin, and mixed solvents of these hydrophilic organic solvents and water can be used. When using a mixed solvent of water and a hydrophilic organic solvent,
In the case of lower alcohol, it is 1 to 90 relative to 10 parts by mass of water.
It is preferable to add 1 to 40 parts by weight to 10 parts by weight of water in the case of a lower aliphatic ketone and 10 to 90 parts by weight to 10 parts by weight of water in the case of a polyhydric alcohol.

Specifically, a treatment tank filled with an extraction solvent is placed in the above-mentioned Ampelopsis of Vineaceae.
s) Add a dried and pulverized product of a genus plant (for example, wisteria tea branches and leaves), stir for 30 minutes to 2 hours to elute soluble components, and filter after filtering if necessary. The solid matter is removed, the extraction solvent is distilled off from the obtained extract, and the extract is obtained by drying. It is preferable that the amount of the extraction solvent is usually 5 to 15 times the amount of the extraction raw material (mass ratio), and the extraction conditions are as follows when water is used as the extraction solvent.
It is usually at 50 to 95 ° C. for about 1 to 4 hours. When a mixed solvent of water and ethanol is used as the extraction solvent, it is usually at 40 to 80 ° C for about 30 minutes to 4 hours.

When the solvent is distilled off from the extract obtained by filtration or centrifugation, a paste-like concentrate is obtained. Further drying gives a solid extract. However, the extract of the plant of the genus Ampelopsis used in the present invention does not have to be a solid extract, and may be in the state of the above extract or its concentrate. These may be used after being purified by a method such as activated carbon treatment, adsorption resin treatment, ion exchange resin, liquid-liquid countercurrent distribution, etc., provided that the object of the present invention is not hindered.

Next, the liver disease therapeutic agent of the present invention, in a second aspect, has at least one of the following general formula (1):
Contains certain dihydroflavonols as active ingredients.

[0026]

[Chemical 3]

In the above formula (1), R ^{1 to} R ⁵ each independently represent a hydrogen atom or a hydroxyl group, and among them, ampelopsin represented by the following formula in which R ^{1 to} R ⁵ are all hydroxyl groups is preferable. .

[0028]

[Chemical 4]

The above ampelopsin is, for example, Fujicha (A
mpelopsis grossedentata),
Large leaf vine (Ampelopsis megaloph)
ylla), Cantonese Grape (Ampelopsis ca)
ntoniensis), Kemponasi (Hovenia)
dulcis), Salix sac
halinensis), Japanese white pine (Pinus c)
ontorta), Erythrophleum af
ricanum and wig (Cercidiphyll)
um japonicum) and can be isolated and purified from an extract of a plant. Of these, Fujicha is preferred.

Specifically, dihydroflavonols, in particular ampelopsin, are Amphelopsis grossedent which is a plant of the genus Ampelopsis.
It can be obtained from ata) as follows. An extract obtained by extracting dried branches and leaves of wisteria tea with water-containing ethanol is concentrated, for example, a porous resin (DIAION HP-
Column chromatography using 20), 80
Ampelopsin is obtained in the fraction eluted with volume% hydrous methanol. This can be further purified by reverse phase silica gel column chromatography or recrystallization.

The dihydroflavonols can be isolated and purified not only by the isolation and purification method described above, but also by a method of precipitating ampelopsin by concentrating the extract, high performance liquid chromatography and the like.

In addition to the compounds isolated and purified as described above, the therapeutic agents for liver diseases of the present invention include Ampelopsi.
An extract of a s genus plant or a crudely purified product at each production stage can be used as well.

In order to use the extract of the genus Ampelopsis plant of the present invention (particularly the extract of wisteria tea) or the dihydroflavonols (particularly ampelopsin) as a prophylactic and therapeutic agent for liver diseases, the product of the present invention is used as a solid or liquid. It can be used by preparing it in a state suitable for oral or parenteral administration (for example, intramuscular injection, intravenous injection, subcutaneous administration, rectal administration, transdermal administration, etc.).

The above solid agents include tablets, capsules,
Granules, powders and fine granules can be prepared, and an enteric coating agent may be prepared by a coating method. Further, the liquid preparation can be prepared by forming a physiologically acceptable salt and then dissolving it in water.

In order to prepare the above-mentioned preparation, a medically acceptable additive may be blended and the preparation can be manufactured according to a conventional method for manufacturing a preparation. As an additive, in the case of an orally administered preparation, an excipient such as starch, lactose, sucrose, corn starch, crystalline cellulose, mannitol, maltitol, etc .;
Disintegrators such as partially pregelatinized starch, croscarmellose sodium, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose; lubricants such as stearic acid, magnesium stearate, calcium stearate, hydrogenated vegetable oil, and talc. .

In the case of a soluble injection for use, an excipient (eg, sodium dihydrogen phosphate, sodium hydrogen phosphate, etc.), a soothing agent (eg, chlorobutanol, xylocaine hydrochloride, etc.) may be added. it can.

The dose of the therapeutic agent for liver diseases of the present invention varies depending on the age of the patient, the type of disease, the degree, etc., and cannot be specified unconditionally, but in the case of oral administration to general adults, Daily dose 20-1000 mg, preferably 50
~ 500 mg. In the case of parenteral administration, it varies depending on the age of the patient, the type of disease, the degree, etc., and cannot be specified unconditionally.
The dose is 00 mg, preferably 5 to 50 mg, and it is preferable to administer it in 1 to 3 divided doses depending on the symptoms.

The liver disease therapeutic agent of the present invention can be used in the fields of food and drink, pharmaceuticals, cosmetics and the like. In this case, the amount of the liver disease therapeutic agent to be added varies depending on the food or drink, cosmetics or pharmaceuticals to be added and cannot be specified unconditionally, but it is usually about 0.01 to 50% by mass.

Examples of the food and drink include soft drinks,
Beverages such as carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks (including concentrated stock solutions and powders for adjustment of these drinks); ice cream, ice sorbet, shaved ice, and other frozen desserts; buckwheat, udon, harusame, gyoza skin, Noodles such as candy skin, Chinese noodles and instant noodles; candy, candy, gum, chocolate, tablet confectionery, snacks, biscuits,
Confectioneries such as jelly, jam, cream, baked goods; processed fish and livestock products such as kamaboko, ham, sausage; dairy products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, Oils and fats and processed foods such as dressings; sauces,
Seasonings such as sauces; other various health and nutritional supplements; tablets, capsules, drinks, pharmaceuticals such as troches, quasi-drugs, etc., and supplements usually used in the production of these It can be added together with various raw materials and additives.

[0040]

EXAMPLES The present invention will be specifically described below with reference to production examples and examples, but the present invention is not limited to the following examples.

[Production Example 1] Production of Fuji Tea Extract (1) Fuji Tea (Ampelopsis glossedenta )
ta) 500 g of a coarsely pulverized product of the dried material of the branches and leaves was added to 5 L of distilled water, and the mixture was extracted with heating under reflux for 2 hours. The obtained extract was concentrated under reduced pressure to obtain a paste. This paste was freeze-dried to obtain 73 g of a powdery extract.

[Production Example 2] Production of Fuji Tea Extract (2) Fuji Tea (Ampelopsis glossedenta )
ta) 500 g of a coarsely pulverized product of the dried material of the branches and leaves was put into 5 L of 50% by volume hydrous ethanol, and the mixture was extracted with heating under reflux for 2 hours. The obtained extract was concentrated under reduced pressure to obtain a paste. This paste is freeze-dried and powdered extract 1
29 g were obtained.

[Production Example 3] Production of Fuji Tea Extract (3) Fuji Tea (Ampelopsis glossedenta )
ta) 500 g of a coarsely crushed product of the dried leaves and leaves was mixed with 5 parts of ethanol.
It was put into L and extracted under heating under reflux for 2 hours. The obtained extract was concentrated under reduced pressure to obtain a paste. The paste was freeze-dried to obtain 26 g of a powdery extract.

[Manufacturing Example 4] Manufacture of Ampelopsin 129 g of the dried Fuji tea extract obtained in Manufacturing Example 2 was passed through a column packed with a porous resin Diaion HP-20 (manufactured by Mitsubishi Chemical), and water and 30 volumes were used. After thoroughly washing with% hydrous methanol, the adsorbed fraction was eluted with 80% hydrous methanol. The solvent was distilled off from this column adsorption portion under reduced pressure to obtain 37.2 g of a solid content. The obtained solid content is used for preparative reverse-phase resin (Fuji Silysia, Chromatorex
ODS DM-1020T) and 30% by volume as a solvent
Fractionation was performed by chromatography using water-containing methanol. Fractions containing this ampelopsin were collected, the solvent was distilled off under reduced pressure, and then recrystallized with water to obtain 10 g.
Got ampelopsin.

Example 1 Galactosamine Induction Test A galactosamine induction test was carried out by the following method using the obtained Fuji tea extract and amperopsin.

The abbreviations used in the following examples have the following meanings. GOT: glutamic oxaloacetic
transminase (glutamic acid oxaloacetate transaminase) GPT: glutamic pyruvic tran
saminese (glutamate pyruvate transaminase) LDH: lactate dehydrogenase
(Lactate dehydrogenase)

<Test animal> 4 weeks old (weight 5
Male Wistar rats purchased from 0 to 55 g) were used in the following galactosamine induction test with 6 rats per group.

<Galactosamine-Inducing Test Method> For the group of rats to which the Fuji tea extract was added and the group of rats to which amperpsin were added, a feed prepared by adding 1% by mass of the Fuji tea extract of Production Example 1 to the basic diet,
Further, a feed prepared by adding 0.1% by mass of ampelopsin to the basic diet was bred by free ingestion, and on the 7th day after the start of the breeding, an aqueous galactosamine solution was intraperitoneally administered at a dose of 40 mg / kg of body weight.

A group of rats with liver injury was given a basic diet ad libitum, and on the 7th day, 40% of galactosamine aqueous solution was added per body weight.
It was intraperitoneally administered at a dose of mg / kg. The group of control rats was given a basic diet ad libitum, and on the 7th day, the same amount of distilled water was intraperitoneally administered.

[0050] A group of liver-injured rats that continued to receive the basic diet after administration of galactosamine, and rats after addition of Fuji tea extract in which the basic diet continued to be supplemented with 1% by mass of the Fuji tea extract of Production Example 1 after administration of galactosamine. Breeding was continued for each of the groups, the ampelopsin-added rat group in which the basic diet was supplemented with 0.1% by mass of ampelopsin, and the control rat group.

22 hours after the administration of galactosamine, blood was collected from the heart under Nembutal anesthesia. Blood was centrifuged at 20000 xg for 20 minutes, and GOT, GPT, LDH activity, liver lipid peroxide (TBARS), and glutathione were measured in the obtained plasma by the following methods. In addition, the amount of weight gain, the amount of food, and the mass of liver were determined. The results are shown in Tables 1 and 2.

The experimental results are shown as the average value ± standard error. Significant differences (P <0.05) between groups were tested using one-way analysis of variance (ANOVA) followed by Duncan's multiple comparison test. In addition, when it was not equal variance, the Mann-Whitney test was used.

<Measurement of Plasma GOT Activity> Plasma GOT activity was measured by measuring the plasma GOT activity of 10 to 1 obtained by the above-mentioned method as a measurement sample.
Using 00 μL, GOT-UV Test Wako (UV-r
ate method, manufactured by Wako Pure Chemical Industries, Ltd.). In the measurement, the change in absorbance at 340 nm was measured with time. When the slope of the change in absorbance is not linear, the addition amount of the sample was reduced until the slope of the change in absorbance became linear, and the same measurement was performed, and the GOT activity value of each sample was calculated based on the addition amount. . In addition, GOT
The activity was expressed in international units (I.U.).

<Measurement of plasma GPT activity> Plasma GPT activity was measured using GPT-UV Test Wako (UV-rat) using 10 to 100 μL of the above-mentioned plasma as a measurement sample.
Method e, manufactured by Wako Pure Chemical Industries, Ltd.) was used to measure GPT activity in the same manner as in the case of plasma GOT activity, and the GPT activity value was determined.

<Measurement of Plasma LDH Activity> Plasma LDH activity was measured by using LDH-UV Test Wako (UV-rat) using 10 to 100 μL of plasma described above as a measurement sample.
The LDH activity value was determined by measuring the plasma GOT activity in the same manner as in the case of plasma GOT activity using the e method, manufactured by Wako Pure Chemical Industries, Ltd.).

<Determination of Liver Lipid Peroxide (TBARS)>
After collecting the blood, 0.5 g of the right lobe of the collected liver was Del Bo
ccio et al.'s method (Atherosclerosis,
81, 127-135. (1990)), 2.
5 mL of ice-cold 0.1 M phosphate buffer (pH 7.4, 1 m
Homogenized in M EDTA). Then, a 2% volume of 2.3% aqueous potassium chloride solution was added to carry out homogenization. Using a part of it, the method of Uchiyama, Yagi et al. (Anal. Biochem., 86, 271-27
8. (1978)), the lipid peroxide was measured.

<Measurement of glutathione> Blood was collected and then
Livers cryopreserved at 70 ° C. were used for the experiment. The frozen liver was homogenized with 10 volumes of 0.4N perchloric acid (containing 2.0 mM EDTA) under ice-cooling, and the homogenization was performed at 5 ° C.
Centrifugation was performed below at 10,000 × g. Add the supernatant to 0.
After filtration through a 2 μm filter, the method of Harvey et al. (Clinica Chemica Acta., 18
0,203-212 (1989)), ion-pair reverse-phase HPLC analysis was performed, and reduced glutathione (GS
H) and oxidized glutathione (GSSG) were quantified.
A Coulochem electrochemical detector was used for detection.

[0058]

[Table 1] Note that different superscripts a to c in Table 1 indicate that the risk rate is <0.0.
5 shows that a significant difference was confirmed between each group.

[0059]

[Table 2] In addition, different superscripts a to b in Table 2 indicate the risk rate <0.0.
5 shows that a significant difference was confirmed between each group.

From the results of Tables 1 and 2, GP was used as an index of liver injury in the experimental liver injury rat induced by galactosamine by adding the Fuji tea extract and amperopsin.
It was confirmed that the elevation of deviating enzymes such as T, GOT, LDH, etc. and the elevation of the amount of peroxide production in the body could be remarkably suppressed, and that it was effective in the prevention and treatment of liver diseases.

[0061]

INDUSTRIAL APPLICABILITY According to the present invention, Ampelo of the vine family
A highly safe, easy-to-use and inexpensive therapeutic agent for a liver disease, which contains an extract of a psis plant (particularly a wisteria tea extract) or a dihydroflavonols (particularly ampelopsin) as an active ingredient, has high safety, is easy to use, and is inexpensive.

Further, the therapeutic agent for liver diseases of the present invention is free from serious side effects unlike conventional drug therapy with antiviral agents, steroid agents, immunostimulants, etc., and is excellent in safety and environmental friendliness. As a natural product-based liver disease therapeutic agent, it can be widely used in the fields of food and drink, pharmaceuticals, cosmetics and the like.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Koji Igarashi             2-18-14 Wakamiyacho, Sakata City, Yamagata Prefecture F term (reference) 4C086 AA01 AA02 BA08 MA01 MA04                       NA14 ZA75 ZB33                 4C088 AB03 AB12 AB56 AC01 BA14                       CA05 CA06 CA11 CA12 CA14                       MA07 NA05 NA14 ZA75 ZB33

Claims (6)

[Claims] 1. A vine family Ampelopsis (Ampelo)
psi) a plant disease extract containing an extract of a genus plant as an active ingredient. 2. A green tea (Ampelopsis gros)
sedentata), large leaf vine (Ampelops)
is megalophylla) and Guangdong snake grape (A
The therapeutic agent for liver diseases according to claim 1, which comprises as an active ingredient an extract obtained by extracting an Ampelopsis plant selected from mpelopsis cantoniensis) with water, a hydrophilic organic solvent or a mixed solvent thereof. 3. A therapeutic agent for liver diseases, which comprises at least one dihydroflavonol represented by the following general formula (1) as an active ingredient. [Chemical 1] (However, in the formula, R ^{1 to} R ⁵ each independently represent a hydrogen atom or a hydroxyl group.) 4. The dihydroflavonols have the general formula
(1) Medium, R¹~ R ⁵Amperop in which all are hydroxyl groups
4. The liver according to claim 3, which is Ampelopsin.
Remedy for visceral diseases. 5. The dihydroflavonols are Fuji tea (Am
pelopsis grossedentata), large leaf vine (Ampelopsis megalophyll)
la), Cantonese Grape (Ampelopsis cant
onionsis), Kemponasi (Hovenia d)
ulcis), Salix sacha
linensis, Yellow pine (Pinus con)
Torta), Erythrophleum afri
canum and wig (Cercidiphyllum)
The therapeutic agent for liver diseases according to claim 3 or 4, which is obtained by isolation and purification from an extract of a plant selected from Japan. 6. The therapeutic agent for a liver disease according to claim 1, which is used for the prevention or treatment of acute or chronic viral hepatitis, acute or chronic drug-induced hepatitis or fulminant hepatitis.