JP7729581B2 - Liver function improver and oral composition for improving liver function - Google Patents

Description

The present invention relates to a liver function improver that contains a compound derived from a natural product as an active ingredient. The present invention also relates to an oral composition for improving liver function that contains the compound.

The liver is an essential organ for life, playing a central role in metabolism. Its main functions include the metabolism of sugars, proteins, lipids, and hormones; detoxifying harmful substances; producing bile; and storing blood. The liver is an organ that rarely shows symptoms even when damaged. However, when liver function is impaired by alcohol consumption, overnutrition, drug abuse, hepatitis viruses, etc., symptoms include fatigue, lethargy, loss of appetite, and even jaundice. Progression of liver dysfunction can lead to lifestyle-related diseases such as hepatitis and cirrhosis. Therefore, improving liver function and protecting it from damage are extremely important for maintaining a healthy lifestyle.

Glutathione is known as a biological component that protects the liver. Glutathione is a tripeptide composed of three amino acids: glutamic acid, cysteine, and glycine. It is a compound with a predominant intracellular cysteine residue. Glutathione is primarily produced in the liver and distributed throughout the body. It plays a role in scavenging intracellular radicals, regulating cellular function through redox, and acting as an SH donor for various enzymes. It is also known to be involved in the detoxification mechanism, particularly in the liver, and to protect liver function. Large amounts of glutathione in the liver are consumed during the process of metabolizing ethanol after drinking alcohol, as well as during the metabolism and detoxification of drugs. Reduced liver glutathione levels can lead to liver dysfunction, including acute and chronic alcoholic hepatitis and drug-induced hepatitis. Reduced systemic glutathione levels can also lead to a variety of symptoms, including cataracts, Parkinson's disease, and the formation of skin blemishes.

Therefore, if glutathione production in the liver (hepatocytes) can be promoted, liver function may be improved and various disorders caused by a decrease in glutathione may be prevented, treated, or improved. Liquiritin (see Patent Document 1) and other substances are known to promote glutathione production in hepatocytes.

Adenosine triphosphate (ATP) is known to improve liver function. ATP is produced by the metabolism of glucose and fat and used as an energy source. The liver uses ATP as an energy source for many chemical reactions, such as the metabolism and detoxification of ethanol and drugs. A decrease in ATP production is thought to reduce the efficiency of these reactions, including metabolism and detoxification, and to result in a lack of energy needed for activities such as labor and exercise, resulting in fatigue.
Therefore, if ATP production in the liver can be promoted, it is thought that it will be possible to prevent or ameliorate various symptoms caused by ethanol intake (e.g., hangover, etc.), prevent, treat, or ameliorate drug-induced liver damage, and promote recovery from fatigue. Extracts of long pepper (see Patent Document 2) and the like are known to have the effect of promoting ATP production in hepatocytes.

Another method for improving liver function is to promote the proliferation of hepatocytes. Although the liver is an organ with a high regenerative capacity, sufficient liver regeneration cannot be expected in conditions of persistent liver dysfunction, such as fatty liver, chronic hepatitis, and cirrhosis. Therefore, if the proliferation of hepatocytes can be efficiently promoted, it is believed that this will lead to the treatment and improvement of liver dysfunction. A combination of pyroglutamic acid and aspartic acid with glutamic acid (see Patent Document 3) is known to have the effect of promoting hepatocyte proliferation.

JP 2009-269889 A JP 2011-184381 A International Publication No. 2014/208381

The present invention aims to find compounds derived from natural products that have an excellent effect in improving liver function, and to provide a liver function improver containing such compounds as active ingredients.
Another object of the present invention is to provide an oral composition for use in improving liver function, which contains a compound derived from a natural product that has an excellent effect in improving liver function.

In order to solve the above problems, the liver function improver of the present invention is characterized by containing a compound represented by the following formula (I) as an active ingredient. Furthermore, the oral composition for improving liver function of the present invention is characterized by incorporating a compound represented by the following formula (I).

According to the present invention, by using the compound represented by formula (I) above as an active ingredient, it is possible to provide a liver function improver having effective effects. Furthermore, by incorporating the compound represented by formula (I) above, it is possible to provide an oral composition suitable for use in improving liver function.

The following describes an embodiment of the present invention.

[Compound (I)]
The liver function improver according to this embodiment contains a compound represented by the following formula (I) as an active ingredient. The oral composition for improving liver function according to this embodiment contains the compound represented by the following formula (I).

The compound represented by formula (I) above is a cinnamic acid derivative also known as 3-(4-hydroxy-3-methoxyphenyl)propionic acid. Hereinafter, in this specification, the compound represented by formula (I) above may be referred to as compound (I).

Compound (I) can be produced, for example, by isolating and purifying from a plant extract containing compound (I). In this case, such a plant extract containing compound (I) can be obtained by a method commonly used for plant extraction. Examples of plants containing compound (I) include rice, barley, wheat, soybeans, adzuki beans, and corn.

Compound (I) can also be produced by fermenting 3-(4-hydroxy-3-methoxyphenyl)propenoic acid or a derivative thereof, or a composition containing the same (e.g., crushed plant material or extract, etc.) with a microorganism having phenolic acid reductase, converting the 3-(4-hydroxy-3-methoxyphenyl)propenoic acid to compound (I), and then extracting, isolating, and purifying the resulting fermentation product. Examples of compositions containing 3-(4-hydroxy-3-methoxyphenyl)propenoic acid include crushed plant material and extracts from plants such as coffee, wheat, corn, tomato, yerba mate, mugwort, and burdock. Furthermore, because 3-(4-hydroxy-3-methoxyphenyl)propenoic acid is a component of lignin in woody and herbaceous plants, lignin or a composition containing it may also be used as the fermentation raw material. On the other hand, examples of microorganisms having phenolic acid reductase include lactic acid bacteria such as Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus crispatus, Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus delbrueckii, Lactobacillus buchneri, Lactobacillus kefiranofaciens, Lactobacillus gallinarum, and Enterococcus faecalis.

The method for extracting, isolating, and purifying compound (I) from the above-mentioned plant or fermented product is not particularly limited, and can be carried out according to conventional methods. For example, the extraction process can be carried out by drying the above-mentioned plant or fermented product as the extraction raw material, and then subjecting it to extraction with an extraction solvent either directly or after pulverizing it using a crusher. Drying can be carried out in the sun or using a commonly used dryer. The raw material can also be used after pretreatment such as degreasing with a nonpolar solvent such as hexane. Pretreatment such as degreasing allows for efficient extraction with a polar solvent.

It is preferable to use a polar solvent as the extraction solvent, such as water or a hydrophilic organic solvent. These can be used alone or in combination of two or more, preferably at room temperature or a temperature below the boiling point of the solvent.

Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, etc., as well as water that has undergone various treatments. Treatments that can be applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, etc. Therefore, water that can be used as an extraction solvent in this embodiment also includes purified water, hot water, ion-exchanged water, saline, phosphate buffer, phosphate-buffered saline, etc.

Hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols with 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; polyhydric alcohols with 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin; and lower aliphatic ketones, such as acetone and methyl ethyl ketone.

When a mixture of two or more polar solvents is used as the extraction solvent, the mixing ratio may be any and can be adjusted appropriately. For example, when a mixture of water and a hydrophilic organic solvent is used as the extraction solvent, the mixture may be mixed at any ratio, i.e., between more than 0:100 and less than 100:0 (volume ratio, hereinafter the same), and can be adjusted appropriately.
For example, when a mixture of water and a lower aliphatic alcohol is used as the extraction solvent, the mixing ratio (volume ratio) of water to lower aliphatic alcohol can be 9:1 or more, or even 7:3 or more, or the mixing ratio of water to lower aliphatic alcohol can be 1:9 or less, or even 2:8 or less. When a mixture of water and a polyhydric alcohol is used, the mixing ratio of water to polyhydric alcohol can be 8:2 or more, or 1:9 or less, and when a mixture of water and a lower aliphatic ketone is used, the mixing ratio of water to lower aliphatic ketone can be 9:1 or more, or 2:8 or less.

The extraction process is not particularly limited as long as it allows the soluble components contained in the extraction raw material to be dissolved in the extraction solvent, and can be carried out according to conventional methods. For example, the extraction raw material is immersed in an extraction solvent in an amount (mass ratio) 5 to 15 times the amount of the extraction raw material, and the soluble components are extracted at room temperature or under reflux heating. The extract can then be obtained by filtering to remove the extraction residue. Distilling the solvent from the resulting extract yields a paste-like concentrate, which can then be further dried to obtain a dried product.

The method for isolating and purifying compound (I) from the extract, concentrate, or dried extract obtained as described above is not particularly limited and can be performed using conventional methods. For example, the extract may be dissolved in a developing solvent and subjected to column chromatography using a porous material such as silica gel or alumina, or a porous resin such as a styrene-divinylbenzene copolymer or polymethacrylate, to recover a fraction containing compound (I). In this case, the developing solvent may be selected appropriately depending on the stationary phase used. For example, when the extract is separated by normal-phase chromatography using silica gel as the stationary phase, the developing solvent may be chloroform:methanol=95:5. Furthermore, the fraction containing compound (I) obtained by column chromatography may be purified using any organic compound purification method, such as reverse-phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, or column chromatography using an ion exchange resin.

[Liver function improver]
The compound (I) obtained as described above has an excellent liver function improving effect and can be used as an active ingredient of a liver function improving agent. Furthermore, the compound (I) can be used to produce a liver function improving agent.
The liver function improver of this embodiment can be used in a wide range of applications, such as pharmaceuticals, quasi-drugs, and cosmetics.

Here, the liver function improving effect of compound (I) is preferably exerted based on the effect of promoting glutathione production in hepatocytes, the effect of promoting adenosine triphosphate (ATP) production in hepatocytes, or the effect of promoting hepatocyte proliferation. However, the liver function improving effect of compound (I) is not limited to the liver function improving effect exerted based on the above effects.

Furthermore, compound (I) can be used to promote glutathione production in hepatocytes, promote ATP production in hepatocytes, or promote hepatocyte proliferation, taking advantage of its hepatocyte glutathione production promoting effect, hepatocyte ATP production promoting effect, or hepatocyte proliferation promoting effect, respectively. In other words, the liver function improver of this embodiment can also be used as a hepatocyte glutathione production promoter, hepatocyte ATP production promoter, or hepatocyte proliferation promoter, containing compound (I) as an active ingredient.

In addition, a composition containing compound (I) may be used as the active ingredient of the liver function improver according to this embodiment, instead of isolated compound (I). Here, "compositions containing compound (I)" in this embodiment include extracts obtained using a plant containing compound (I) as an extraction raw material, fermented products containing compound (I), and extracts obtained using the fermented products as an extraction raw material. Furthermore, "extracts" include extracts obtained by extraction treatment, diluted or concentrated solutions of the extracts, and dried products obtained by drying the extracts.

When a composition containing compound (I) is used as the active ingredient of the liver function improver according to this embodiment, the content of compound (I) in the composition is preferably 0.1% by mass or more, more preferably 5% by mass or more, and particularly preferably 50% by mass or more. By using compound (I) with a higher purity as the active ingredient, a liver function improver with even better effects can be obtained.

The liver function improver of this embodiment may consist solely of compound (I) or a composition containing compound (I), or may be a formulation of compound (I) or a composition containing compound (I).

The liver function improver of this embodiment can be formulated into any dosage form, such as powder, granules, tablets, or liquid, using a pharmaceutically acceptable carrier such as dextrin or cyclodextrin, or any other auxiliary agent, according to standard methods. In this case, examples of auxiliary agents that can be used include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring/flavoring agents. The liver function improver can be incorporated into other compositions (such as the oral composition described below) and used, or can be used as an external liquid preparation, patch, or the like.

When the liver function improver of this embodiment is formulated, the content of compound (I) or a composition containing compound (I) is not particularly limited and can be set appropriately depending on the purpose.

If necessary, the liver function improver of this embodiment can be used as an active ingredient by blending other natural extracts or the like that have liver function improving effects with compound (I) or a composition containing compound (I).

The liver function improver of this embodiment can be administered to patients by oral administration, intraperitoneal administration, intravenous administration, subcutaneous administration, etc., and a method suitable for prevention or treatment may be selected appropriately depending on the type of disease. Furthermore, the dosage of the liver function improver of this embodiment may be increased or decreased as appropriate depending on the type and severity of the disease, individual patient differences, administration method, administration period, etc.

The liver function improver of this embodiment can improve liver function by the action of the active ingredient, compound (I). Uses for improving liver function include: prevention, treatment, or amelioration of symptoms caused by ethanol intake (e.g., hangover); prevention, treatment, or amelioration of fatty liver, hepatitis such as alcoholic hepatitis and drug-induced hepatitis, liver cirrhosis, etc.
However, in addition to these uses, the liver function improver of this embodiment can be used for all uses in which it is significant to exert a liver function improving effect, preferably an effect of promoting hepatocyte glutathione production, an effect of promoting hepatocyte ATP production, or an effect of promoting hepatocyte proliferation.

For example, the liver function improver of this embodiment or the aforementioned hepatocyte glutathione production promoter can be used for the prevention, treatment, or amelioration of diseases associated with decreased in vivo glutathione levels, such as cataracts and Parkinson's disease, through the hepatocyte glutathione production-promoting activity of compound (I).

Furthermore, the liver function improver of this embodiment or the hepatocyte ATP production promoter described above can be used for purposes such as relieving fatigue and lethargy through the hepatocyte ATP production promoting effect of compound (I).

The liver function improver of this embodiment or the aforementioned hepatocyte proliferation promoter can be used in applications such as liver regenerative medicine through the hepatocyte proliferation-promoting activity of compound (I).

Furthermore, since the liver function improver of this embodiment has excellent effects in improving liver function, it can also be suitably used as a reagent for research into these mechanisms of action.

[Oral composition for improving liver function]
Compound (I) has an excellent effect in improving liver function, and is therefore suitable for incorporation into oral compositions. In this case, compound (I) or a composition containing compound (I) may be incorporated as is, or a liver function improver formulated from compound (I) may be incorporated.

By incorporating compound (I) or a composition containing compound (I), or a liver function improver formulated from compound (I) or a composition containing compound (I), into an oral composition, an oral composition suitable for improving liver function can be created. The above-mentioned effects are preferably achieved by imparting them to an oral composition, as their effects are more easily exerted.

Here, oral compositions refer to those that are unlikely to pose a risk to human health and are taken orally or by gastrointestinal administration in normal social life, and are not limited to administrative classifications such as food, medicine, or quasi-drug. Therefore, in this embodiment, "oral compositions" broadly encompass orally taken general foods, feeds, health foods, health functional foods (foods for specified health uses, foods with nutrient claims, foods and beverages with functional claims), quasi-drugs, medicines, etc. The oral compositions of this embodiment are preferably oral compositions that can display the favorable effects of compound (I) on the oral composition or its packaging, and are particularly preferably health functional foods (foods for specified health uses, foods with functional claims, foods with nutrient claims), quasi-drugs, or medicines.

When compound (I) or a composition containing compound (I), or a liver function improver formulated from compound (I) or a composition containing compound (I), is incorporated into an oral composition, the amount of active ingredient can be adjusted as appropriate, taking into account the intended use, symptoms, gender, etc. However, taking into account the general intake of the oral composition to which it is to be added, it is preferable to adjust the amount of compound (I) so that the daily intake per adult is approximately 1 to 1,000 mg. When the oral composition to which it is to be added is in the form of granules, tablets, or capsules, the amount of compound (I) or a composition containing compound (I), or a liver function improver formulated from compound (I) or a composition containing compound (I), added is typically 0.1 to 100% by mass, and preferably 5 to 100% by mass, of the oral composition to which it is to be added.

The oral composition of this embodiment may be any oral composition containing compound (I) that does not interfere with its activity, or may be a dietary supplement containing compound (I) as a main ingredient.

When producing the oral composition of this embodiment, any desired form of oral composition can be prepared by adding any desired auxiliary agent, such as sugars such as dextrin and starch; proteins such as gelatin, soy protein and corn protein; amino acids such as alanine, glutamine and isoleucine; polysaccharides such as cellulose and gum arabic; or fats and oils such as soybean oil and medium-chain fatty acid triglycerides.

Oral compositions that can incorporate compound (I) are not particularly limited, but specific examples include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (including concentrated concentrates and powders for adjusting these beverages); frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, vermicelli, gyoza wrappers, shumai wrappers, Chinese noodles, and instant noodles; sweets such as candy, chewing gum, candy, chewing gum, chocolate, tablet candy, snacks, biscuits, jelly, jam, cream, and baked goods; Examples of such products include processed seafood and livestock foods such as maboko, ham, and sausage; dairy products such as processed milk and fermented milk; oils and fats and processed oil foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing; seasonings such as sauces and dressings; soups, stews, salads, side dishes, and pickles; and various other forms of health and nutritional supplements; tablets, capsules, and drinks. When compound (I) is formulated into these oral compositions, commonly used auxiliary ingredients and additives can also be used in combination.

The liver function enhancer and oral composition for improving liver function of this embodiment are preferably applied to humans, but can also be applied to animals other than humans (e.g., mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.) as long as their respective functional effects are achieved.

The present invention will be explained in detail below using test examples, but the present invention is not limited to the following examples. In these test examples, compound (I) (Tokyo Chemical Industry Co., Ltd., 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid, Sample 1) was used as the test sample.

Test Example 1 Test for Promoting Activity of Glutathione Production in Hepatocytes Compound (I) (Sample 1) was tested for its activity of promoting glutathione production in hepatocytes as follows.

Normal human hepatocytes (hepatocytes) were cultured in 10% FBS-containing Dulbecco's modified Eagle's medium (DMEM) and then harvested by trypsinization. The harvested cells were diluted with 10% FBS-containing DMEM to a cell density of 1.0 x ¹⁰ cells/mL, and then seeded in a 48-well plate at 200 μL per well and cultured overnight.

After incubation, 200 μL of the test sample (Sample 1, see Table 1 below for final concentration) dissolved in 1% FBS-containing DMEM was added to each well, and incubation continued for another 24 hours. As a control, incubation was performed in the same manner using 1% FBS-containing DMEM without sample. After incubation, the medium was removed from each well, and the wells were washed with 400 μL of PBS(-). The cells were then lysed using 150 μL of M-PER (PIERCE).

Total glutathione was quantified using 100 μL of this solution. Specifically, 100 μL of cell extract, 50 μL of 0.1 mol/L phosphate buffer, 25 μL of 2 mmol/L NADPH, and 25 μL of 3.2 units/mL glutathione reductase were added to a 96-well plate and incubated at 37°C for 10 minutes. After this, 25 μL of 10 mmol/L 5,5'-dithiobis(2-nitrobenzoic acid) was added. Absorbance at 412 nm was measured for 5 minutes, and ΔOD/min was calculated. Total glutathione concentration was calculated based on a calibration curve prepared using oxidized glutathione (Fujifilm Wako Pure Chemical Industries, Ltd.). The obtained values were corrected for the amount of glutathione per total protein, and the glutathione production promotion rate (%) was calculated using the following formula:

Glutathione production promotion rate (%) = B/A x 100
The terms in the formula represent the following:
A: Amount of glutathione per total protein amount in cells to which no sample was added. B: Amount of glutathione per total protein amount in cells to which a test sample was added. The results are shown in Table 1.

As shown in Table 1, compound (I) (sample 1) was found to have an excellent effect of promoting glutathione production in hepatocytes.

[Test Example 2] Test of ATP production promoting effect in hepatocytes Compound (I) (sample 1) was tested for its ATP production promoting effect in hepatocytes as follows.

Normal human hepatocytes (hepatocytes) were cultured in 10% FBS-containing Dulbecco's modified Eagle's medium (DMEM) and then harvested by trypsinization. The harvested cells were diluted with 10% FBS-containing DMEM to a cell density of 2.0 x ¹⁰ cells/mL, and then seeded in a 96-well plate at 100 μL per well and cultured overnight.

After incubation, the medium was removed, and 100 μL of the test sample (Sample 1, see Table 2 below for final concentration) dissolved in 10% FBS-containing DMEM was added to each well and incubated for 2 hours. As a control, incubation was performed in the same manner using 10% FBS-containing DMEM without the sample.

The ATP production promotion effect was evaluated by measuring the amount of intracellular ATP using the firefly luciferase luminescence method. After 2 hours of incubation, 100 μL of ATP measurement reagent (manufactured by Toyo B-Net Co., Ltd., product name "Cellular ATP Measurement Reagent") was added to each well, and a luciferase-mediated chemiluminescence reaction was carried out. After the reaction, the amount of chemiluminescence, which was proportional to the amount of intracellular ATP, was measured using a chemiluminescence measurement device (manufactured by Thermo Fisher Scientific, product name: Varioskan LUX Multimode Microplate Reader). From the results obtained, the ATP production promotion rate (%) was calculated using the following formula:

ATP production promotion rate (%) = A/B x 100
The terms in the formula represent the following:
A: Amount of chemiluminescence in cells to which a test sample was added B: Amount of chemiluminescence in cells to which no sample was added The results are shown in Table 2.

As shown in Table 2, compound (I) (sample 1) was found to have an excellent effect of promoting ATP production in hepatocytes.

[Test Example 3] Test for promoting hepatocyte proliferation Compound (I) (sample 1) was tested for promoting hepatocyte proliferation as follows.

Normal human hepatocytes were cultured in 10% FBS-containing Dulbecco's modified Eagle's medium (DMEM) and then harvested by trypsinization. The harvested cells were diluted with 1% FBS-containing DMEM to a cell density of 1.25 x ¹⁰ cells/mL, and then seeded in a 96-well plate at 100 μL per well and cultured overnight.

After incubation, the medium was removed, and 200 μL of the test sample (Sample 1, see Table 3 below for final concentration) dissolved in 1% FBS-containing DMEM was added to each well, followed by incubation for an additional 3 days. As a control, incubation was performed in the same manner using 1% FBS-containing DMEM without the sample.

After incubation, the hepatocyte proliferation-promoting effect was measured using an MTT assay. Specifically, the medium was removed, and 100 μL of 0.4 mg/mL MTT prepared in PBS(-) was added to each well. After incubation for a further 2 hours, the blue formazan produced within the cells was extracted with 100 μL of 2-propanol. The absorbance of this extract was measured at 570 nm, where the absorption maximum of blue formazan is located. At the same time, the absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was used to determine the amount of blue formazan produced. From the measurement results, the hepatocyte proliferation promotion rate (%) was calculated using the following formula:

Hepatocyte proliferation promotion rate (%) = A/B x 100
The terms in the formula represent the following:
A: Amount of blue formazan produced in cells to which a test sample was added. B: Amount of blue formazan produced in cells to which no sample was added. The results are shown in Table 3.

As shown in Table 3, compound (I) (sample 1) was found to have excellent hepatocyte proliferation-promoting activity.

[Formulation example 1]
Tablets having the following composition were prepared by a conventional method.
Compound (I) 5.0 mg
Dolomite (contains 20% calcium and 10% magnesium) 83.4 mg
Casein phosphopeptide 16.7mg
Vitamin C 33.4mg
Maltitol 136.8mg
Collagen 12.7mg
Sucrose fatty acid ester 12.0 mg

[Formulation example 2]
Capsules having the following composition were prepared by a conventional method. No. 1 hard gelatin capsules were used.
<Composition in 1 capsule (1 tablet 200 mg)>
Compound (I) 10.0 mg
Cornstarch 70.0mg
Lactose 100.0mg
Calcium lactate 10.0 mg
Hydroxypropyl cellulose (HPC-L) 10.0 mg

[Formulation example 3]
An oral liquid preparation having the following composition was prepared by a conventional method.
<Composition in 1 ampoule (100 mL each)>
Compound (I) 0.3% by mass
Sorbitol 12.0% by mass
Sodium benzoate 0.1% by mass
Fragrance 1.0% by mass
Calcium sulfate 0.5% by mass
Purified water remainder (100% by mass)

The liver function improver and oral composition for improving liver function of this embodiment of the present invention can improve liver function, thereby making a significant contribution to: the prevention, treatment, or amelioration of symptoms caused by ethanol intake (e.g., hangovers); the prevention, treatment, or amelioration of fatty liver, hepatitis such as alcoholic hepatitis and drug-induced hepatitis, and liver cirrhosis; etc.

Claims (2)

The compound represented by the following formula (I) is used as an active ingredient:
Used to improve liver function by promoting glutathione production in hepatocytes and/or promoting hepatocyte proliferation
A liver function improver characterized by:
A compound represented by the following formula (I) is blended ,
Used to improve liver function by promoting glutathione production in hepatocytes and/or promoting hepatocyte proliferation
An oral composition for improving liver function, characterized by: