JP2022129479A - Liver function improvers and liver function-improving oral compositions - Google Patents

Abstract

To discover, among compounds derived from natural products, those having excellent effect regarding liver function-improving effect, and provide liver function improvers containing them as active ingredients.SOLUTION: A compound represented by the formula (I) in the figure is used as an active ingredient of a liver function improver. A compound represented by the formula (I) is contained in a liver function-improving oral composition.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to a liver function improving agent containing a compound derived from a natural product as an active ingredient. Furthermore, the present invention also relates to an oral composition for improving liver function containing the compound.

The liver is an essential organ that plays a central role in metabolism and is essential for life support. Its main functions alone include metabolism of sugars, proteins, lipids, and hormones, detoxification of harmful substances, production of bile, and storage of blood. is mentioned. The liver is an organ that does not easily show symptoms even when damaged. Furthermore, jaundice and the like may be present. Progression of liver dysfunction may lead to lifestyle-related diseases such as hepatitis and liver cirrhosis, and it is extremely important to improve liver function and protect it from disorders in order to maintain a healthy life.

Glutathione is known as an in vivo component that protects the liver. Glutathione is a tripeptide consisting of three amino acids, glutamic acid, cysteine and glycine, and is the compound with the major intracellular cysteine residue. Glutathione is mainly produced in the liver and supplied to the whole body. In addition to capturing radicals in cells, regulating cellular functions by redox, and acting as an SH donor for various enzymes, glutathione plays a detoxifying mechanism especially in the liver. known to participate and protect liver function. A large amount of glutathione in the liver is consumed during the process of alcohol metabolism and drug metabolism/detoxification. In addition, it is known that the amount of glutathione in the whole body decreases, which causes various symptoms such as cataracts, Parkinson's disease, and spots on the skin.

Therefore, if the production of glutathione in the liver (hepatocytes) can be promoted, it is expected that liver function will be improved, and that various disorders caused by glutathione depletion will be prevented, treated or improved. Liquiritin (see Patent Document 1) and the like are known to have glutathione production-promoting action in hepatocytes.

Adenosine triphosphate (ATP) is known as a component that improves liver function. ATP is produced by metabolism of glucose and fat and used as an energy source. In the liver, ATP is used as an energy source for many chemical reactions that occur in the liver, such as the metabolism and detoxification of ethanol and drugs. In addition, it is thought that the energy required for activities such as work and exercise is insufficient, resulting in fatigue.
Therefore, if the production of ATP in the liver can be promoted, various symptoms caused by ethanol intake (for example, hangovers) can be prevented or improved, liver damage caused by drugs can be prevented, treated or improved, and recovery from fatigue can be achieved. can be promoted. Hihatsu extract (see Patent Document 2) and the like are known to have an ATP production-promoting effect in hepatocytes.

In addition, methods for improving liver function include methods for promoting proliferation of hepatocytes. Although the liver is an organ with high regenerative ability, sufficient liver regeneration cannot be expected in the state 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 it will lead to the treatment and improvement of liver dysfunction. Pyroglutamic acid and combinations with aspartic acid and glutamic acid (see Patent Document 3) are known to have hepatocyte proliferation-promoting action.

JP 2009-269889 A JP 2011-184381 A WO2014/208381

An object of the present invention is to find compounds having excellent liver function-enhancing action among natural products-derived compounds, and to provide liver function-enhancing agents containing these 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 natural product-derived compound having an excellent liver function-improving action.

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

According to the present invention, by using the compound represented by the above formula (I) as an active ingredient, it is possible to provide a liver function improving agent having action and effect. Furthermore, by blending the compound represented by the above formula (I), an oral composition suitable for improving liver function can be provided.

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below.

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

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

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

Compound (I) is, for example, 3-(4-hydroxy-3-methoxyphenyl)propenoic Acid (3-(4-Hydroxy-3-methoxyphenyl)propenoic Acid) or a derivative thereof, or a composition containing these (such as , plant crush or extract, etc.) is fermented with a microorganism having phenolic acid reductase to convert 3-(4-hydroxy-3-methoxyphenyl)propenoic acid to compound (I), and then obtained It can also be produced by extracting, isolating and purifying the fermented product. Compositions containing 3-(4-hydroxy-3-methoxyphenyl)propenoic acid include, for example, crushed products and extracts of plants such as coffee, wheat, corn, tomato, mate, mugwort, and burdock. . In addition, since 3-(4-hydroxy-3-methoxyphenyl)propenoic acid is a constituent of lignin in woody plants and herbaceous plants, lignin or a composition containing it may be used as a raw material for fermentation. On the other hand, examples of microorganisms having phenolic acid reductase include Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus crispatus, Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus delbrueckii, Lactobacillus buchneri, Lactobacillus kefiranofaciens, Lactobacillus faecalilocus gallinarum, and Enterobacillus gallinarum. and lactic acid bacteria.

The method for extracting, isolating and purifying compound (I) from the plant or fermented product is not particularly limited, and can be carried out according to a conventional method. For example, the extraction process may be carried out by drying the plant or fermented product as the raw material for extraction, and then subjecting it to extraction with an extraction solvent, either as it is or pulverized using a coarse crusher. Drying may be performed in the sun or using a commonly used dryer. In addition, it may be used as an extraction raw material after being subjected to pretreatment such as degreasing with a non-polar solvent such as hexane. By performing pretreatment such as degreasing, the extraction treatment with a polar solvent can be efficiently performed.

As the extraction solvent, it is preferable to use a polar solvent, for example, water, hydrophilic organic solvents, etc., which are used alone or in combination of two or more at room temperature or at a temperature below the boiling point of the solvent. is preferred.

Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Treatments applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic adjustment, buffering, and the like. Therefore, water that can be used as an extraction solvent in the present embodiment includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, and the like.

Hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; 2 to 5 polyhydric alcohols; 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 is arbitrary and can be adjusted as appropriate. For example, when a mixture of water and a hydrophilic organic solvent is used as an extraction solvent, it can be mixed at an arbitrary ratio, that is, more than 0:100 and less than 100:0 (volume ratio, hereinafter the same). It can be used in various ways, and can be adjusted as appropriate.
For example, when a mixture of water and a lower aliphatic alcohol is used as an extraction solvent, the mixing ratio (volume ratio) of water and the lower aliphatic alcohol can be 9: 1 or more, and further 7 :3 or more, or the mixing ratio of water and lower aliphatic alcohol can be 1:9 or less, further 2:8 or less. Further, when using a mixed solution of water and polyhydric alcohol, the mixing ratio of water and polyhydric alcohol can be 8:2 or more, or 1:9 or less, and water and lower aliphatic ketone When using a mixture of water and lower aliphatic ketone, the mixing ratio of water and lower aliphatic ketone can be 9:1 or more, or 2:8 or less.

The extraction treatment is not particularly limited as long as the soluble components contained in the raw material for extraction can be eluted into the extraction solvent, and can be carried out according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent of 5 to 15 times the amount (mass ratio) of the extraction raw material, the soluble component is extracted at room temperature or under reflux heating, and then filtered to remove the extraction residue. You can get the liquid. A paste-like concentrate is obtained by distilling off the solvent from the obtained extract, and a dried product is obtained by further drying the concentrate.

The method for isolating and purifying compound (I) from the extract obtained as described above, the concentrate of the extract, or the dried extract is not particularly limited, and is carried out by a conventional method. be able to. For example, the extract is 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 styrene-divinylbenzene copolymer or polymethacrylate to obtain compound (I ), and the like. In this case, the developing solvent may be appropriately selected according to 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 is chloroform:methanol=95: 5 and the like. Furthermore, the fraction containing compound (I) obtained by column chromatography is subjected to reverse phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, column chromatography using an ion exchange resin, etc. Any organic compound purification means may be used for purification.

[Hepatic Function Improving Agent]
Since compound (I) obtained as described above has an excellent liver function-improving action, it can be used as an active ingredient of a liver function-improving agent. Compound (I) can also be used to produce a liver function improving agent.
The liver function improving agent of this embodiment can be used in a wide range of applications such as pharmaceuticals, quasi-drugs, and cosmetics.

Here, the hepatic function-improving action of compound (I) is preferably exhibited based on hepatocyte glutathione production-promoting action, hepatocyte adenosine triphosphate (ATP) production-promoting action, or hepatocyte proliferation-promoting action. . However, the hepatic function-enhancing action of compound (I) is not limited to the hepatic function-enhancing action exhibited based on the above action.

Further, compound (I) utilizes its hepatocyte glutathione production promoting action, hepatocyte ATP production promoting action, or hepatocyte proliferation promoting action, respectively, for hepatocyte glutathione production promotion use, hepatocyte ATP production promotion use, or It can be used for promoting hepatocyte proliferation. That is, the liver function improving agent of the present 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.

A composition containing compound (I) may be used instead of isolated compound (I) as the active ingredient of the liver function improving agent according to the present embodiment. Here, the "composition containing compound (I)" in the present embodiment includes an extract obtained by using a plant containing compound (I) as an extraction raw material, a fermented product containing compound (I), and the Extracts obtained by using fermented products as extraction raw materials are included. In addition, the "extract" includes an extract obtained by an extraction process, a diluted or concentrated liquid of the extract, or a dried product obtained by drying the extract.

When a composition containing compound (I) is used as an active ingredient of the liver function improving agent according to the present embodiment, compound (I) is preferably 0.1% by mass or more in the composition. It is more preferably at least 50% by mass, particularly preferably at least 50% by mass. By using the purified compound (I) as an active ingredient, it is possible to obtain a liver function improving agent with even more excellent effects.

The liver function-enhancing agent of the present embodiment may consist of compound (I) or a composition containing compound (I) alone, or may be formulated from compound (I) or a composition containing compound (I). Anything is fine.

The liver function improving agent of the present embodiment can be prepared in any form of powder, granules, tablets, liquid, etc., according to a conventional method, using a pharmaceutically acceptable carrier such as dextrin, cyclodextrin, or any other adjuvant. It can be formulated into dosage forms. At this time, as auxiliary agents, for example, excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like can be used. The liver function-enhancing agent can be used by blending it with other compositions (for example, oral compositions to be described later), and can also be used as external liquid preparations, patches, and the like.

When the liver function improving agent of the present embodiment is formulated, the content of compound (I) or the composition containing compound (I) is not particularly limited, and can be appropriately set according to the purpose. can.

In addition, the liver function improving agent of the present embodiment is effective when combined with compound (I) or a composition containing compound (I), such as another natural extract having a liver function improving effect, if necessary. It can be used as an ingredient.

Methods for administering the agent for improving liver function of the present embodiment to patients include oral administration, intraperitoneal administration, intravenous administration, subcutaneous administration, etc. Depending on the type of disease, a suitable method for prevention or treatment thereof may be used. can be selected as appropriate. In addition, the dose of the liver function improving agent of the present embodiment may also be appropriately increased or decreased depending on the type and severity of disease, individual patient differences, administration method, administration period, and the like.

The hepatic function improving agent of the present embodiment can improve hepatic function due to the action of compound (I), which is an active ingredient. Uses for improving liver function include: prevention, treatment, or improvement of symptoms caused by ethanol intake (for example, hangovers); improvement;
However, in addition to these uses, the liver function improving agent of the present embodiment exhibits a liver function improving effect, preferably a hepatocyte glutathione production promoting effect, a hepatocyte ATP production promoting effect, or a hepatocyte proliferation promoting effect. It can be used for all applications that are particularly meaningful.

For example, the hepatic function-enhancing agent of the present embodiment or the aforementioned hepatocyte glutathione production-enhancing agent is associated with cataracts, Parkinson's disease, etc., and a decrease in in vivo glutathione concentration through the hepatocyte glutathione production-enhancing action of compound (I). It can be used for purposes such as prevention, treatment, or amelioration of diseases.

In addition, the hepatic function-improving agent of the present embodiment or the hepatocyte ATP production promoter described above can be used for purposes such as recovery from fatigue and malaise through the hepatocyte ATP production-promoting action of compound (I). .

The hepatic function-enhancing agent of the present embodiment or the aforementioned hepatocyte proliferation-promoting agent can be used for applications such as liver regenerative medicine through the hepatocyte proliferation-promoting action of compound (I).

In addition, since the liver function-enhancing agent of the present embodiment has excellent liver function-enhancing action, it can be suitably used as a reagent for research on these mechanisms of action.

[Oral composition for improving liver function]
Since compound (I) has an excellent liver function-enhancing action, it is suitable for formulation into an oral composition. In this case, compound (I) or a composition containing compound (I) may be blended as it is, or a liver function improving agent formulated from compound (I) may be blended.

By incorporating compound (I) or a composition containing compound (I), or a liver function improving agent formulated from compound (I) or a composition containing compound (I) into an oral composition, liver function It can be an oral composition suitable for enhancement applications. The above action is suitable because it is likely to exert its action and effect when it is imparted to an oral composition.

Here, the term “oral composition” refers to a composition that poses little danger to human health and is taken orally or through the gastrointestinal tract in normal social life. It is not limited to categories such as products. Therefore, the "oral composition" in the present embodiment includes orally ingested general foods, feeds, health foods, foods with health claims (foods for specified health uses, foods with nutrient function claims, foods and drinks with function claims), quasi-drugs It includes a wide range of products, pharmaceuticals, etc. The oral composition according to the present embodiment is preferably an oral composition capable of displaying the preferred action of compound (I) on the oral composition or its packaging, and is a food with health claims (food for specified health uses). , Foods with Function Claims, Foods with Nutrient Claims), quasi-drugs or pharmaceuticals are particularly preferred.

When Compound (I) or a composition containing Compound (I), or a liver function improving agent formulated from Compound (I) or a composition containing Compound (I) is incorporated into an oral composition, the effectiveness thereof The amount of the ingredients can be changed as appropriate in consideration of the purpose of use, symptoms, gender, etc. A daily intake of about 1 to 1000 mg is preferred. In addition, when the oral composition to be added is a granular, tablet-shaped or capsule-shaped oral composition, compound (I) or a composition containing compound (I), or compound (I) or containing compound (I) The amount of the liver function improving agent formulated from the composition to be added is usually 0.1 to 100% by mass, preferably 5 to 100% by mass, relative to the oral composition to be added.

The oral composition of the present embodiment may be one in which compound (I) is blended into any oral composition that does not interfere with its activity, or a nutritional supplement containing compound (I) as a main ingredient. There may be.

When producing the oral composition of the present embodiment, for example, sugars such as dextrin and starch; proteins such as gelatin, soybean protein and corn protein; amino acids such as alanine, glutamine and isoleucine; Polysaccharides; oils and fats such as soybean oil, medium-chain triglycerides, and the like can be added to give any form of oral composition.

The oral composition in which compound (I) can be blended is not particularly limited, but specific examples thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (concentrated undiluted solutions of these drinks and preparations for preparation). frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as buckwheat, udon, vermicelli, gyoza skin, dumpling skin, shumai skin, Chinese noodles, instant noodles; candy, chewing gum, candy, gum, chocolate, tablets Confectionery such as sweets, snacks, biscuits, jellies, jams, creams, and baked goods; Processed marine and livestock foods such as fish cakes, hams, and sausages; Dairy products such as processed milk and fermented milk; Salad oil, tempura oil, margarine, and mayonnaise , shortening, whipped cream, dressings and other oils and fats processed foods; sauces, sauces and other seasonings; soups, stews, salads, side dishes, pickles; other health and nutritional supplements in various forms; tablets, capsules, drinks When formulating compound (I) into these oral compositions, commonly used auxiliary raw materials and additives can be used in combination.

In addition, the liver function improving agent and the oral composition for improving liver function of the present embodiment are preferably applied to humans, but as long as their respective effects are exhibited, animals other than humans (e.g., , mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.).

The present invention will be specifically described below with reference to test examples, but the present invention is not limited to the following examples. In this test example, compound (I) (manufactured by Tokyo Chemical Industry Co., Ltd., 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid, sample 1) was used as a test sample.

[Test Example 1] Glutathione production promoting effect test in hepatocytes Compound (I) (Sample 1) was tested for glutathione production promoting effect in hepatocytes as follows.

Normal human hepatocytes (Hepatocytes) were cultured using 10% FBS-containing Dulbecco's Modified Eagle's Medium (DMEM), and then the cells were collected by trypsinization. After diluting the collected cells with DMEM containing 10% FBS to a cell density of 1.0×10 ⁵ cells/mL, 200 μL of each well was seeded in a 48-well plate and cultured overnight.

After culturing, 200 μL of a test sample (Sample 1, see Table 1 below for final concentration) dissolved in DMEM containing 1% FBS was added to each well and cultured for an additional 24 hours. As a control, DMEM containing 1% FBS to which no sample was added was used and cultured in the same manner. After culturing, the medium was removed from each well, washed with 400 μL of PBS(−), and then the cells were lysed using 150 μL of M-PER (manufactured by PIERCE).

100 μL of this was used to quantify total glutathione. That is, 100 μL of cell extract dissolved in a 96-well plate, 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 and heated at 37° C. for 10 minutes. , 25 μL of 10 mmol/L 5,5′-dithiobis(2-nitrobenzoic acid) was added, and absorbance at a wavelength of 412 nm was measured for 5 minutes to obtain ΔOD/min. The total glutathione concentration was calculated based on a calibration curve prepared using oxidized glutathione (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). After correcting the obtained value to the amount of glutathione per total protein amount, the glutathione production acceleration rate (%) was calculated based on the following formula.

Glutathione production promotion rate (%) = B / A × 100
Each term in the formula represents the following.
A: Glutathione amount per total protein amount in cells to which no sample was added B: Glutathione amount per total protein amount in cells to which the test sample was added Table 1 shows the results.

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

[Test Example 2] ATP production promoting action test in hepatocytes Compound (I) (Sample 1) was tested for ATP production promoting action in hepatocytes as follows.

Normal human hepatocytes (Hepatocytes) were cultured using 10% FBS-containing Dulbecco's Modified Eagle's Medium (DMEM), and then the cells were collected by trypsinization. After diluting the recovered cells with DMEM containing 10% FBS to a cell density of 2.0×10 ⁵ cells/mL, 100 μL of each well was seeded in a 96-well plate and cultured overnight.

After the culture was completed, the medium was removed, and 100 μL of a test sample (Sample 1, see Table 2 below for final concentration) dissolved in DMEM containing 10% FBS was added to each well and cultured for 2 hours. As a control, DMEM containing 10% FBS to which no sample was added was used and cultured in the same manner.

The ATP production promoting action was evaluated by measuring the amount of intracellular ATP using the firefly luciferase luminescence method. That is, after culturing for 2 hours, 100 μL of an ATP measurement reagent (manufactured by Toyo Benet Co., Ltd., trade name ““Cellular” ATP measurement reagent”) was added to each well, and a chemiluminescence reaction using luciferase was performed. After the reaction, the amount of chemiluminescence 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 obtained results, the ATP production promotion rate (%) was calculated by the following formula.

ATP production promotion rate (%) = A/B x 100
Each term in the formula represents the following.
A: Amount of chemiluminescence in cells to which the test sample was added B: Amount of chemiluminescence in cells to which no sample was added Table 2 shows the results.

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

[Test Example 3] Hepatocyte proliferation-promoting action test Compound (I) (Sample 1) was tested for hepatocyte proliferation-promoting action as follows.

Normal human hepatocytes were cultured using 10% FBS-containing Dulbecco's Modified Eagle's Medium (DMEM), and then the cells were harvested by trypsinization. After diluting the recovered cells with DMEM containing 1% FBS to a cell density of 1.25×10 ⁴ cells/mL, 100 μL of each well was seeded in a 96-well plate and cultured overnight.

After the culture was completed, the medium was removed, and 200 μL of a test sample (Sample 1, see Table 3 below for final concentration) dissolved in DMEM containing 1% FBS was added to each well and cultured for 3 days. As a control, DMEM containing 1% FBS to which no sample was added was used and cultured in the same manner.

After completion of the culture, hepatocyte proliferation-promoting action was measured by MTT assay. Specifically, the medium was removed, 100 μL of 0.4 mg/mL MTT prepared with PBS(-) was added to each well, and after culturing for 2 hours, blue formazan produced in the cells was extracted with 100 μL of 2-propanol. did. The absorbance of this extract was measured at 570 nm where the absorption maximum of blue formazan exists. At the same time, absorbance at a wavelength of 650 nm was measured as turbidity, and the difference between the two was taken as the amount of blue formazan produced. From the measurement results, hepatocyte proliferation promotion rate (%) was calculated based on the following formula.

Hepatocyte proliferation promotion rate (%) = A/B x 100
Each term in the formula represents the following.
A: Amount of blue formazan produced in cells to which the test sample was added B: Amount of blue formazan produced in cells to which no sample was added Table 3 shows the results.

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

[Formulation Example 1]
A tablet having the following composition was produced by a conventional method.
Compound (I) 5.0 mg
Dolomite (containing 20% calcium and 10% magnesium) 83.4mg
Casein phosphopeptide 16.7mg
Vitamin C 33.4mg
Maltitol 136.8mg
Collagen 12.7mg
Sucrose fatty acid ester 12.0mg

[Formulation Example 2]
A capsule having the following composition was produced by a conventional method. As the capsules, 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 per bottle)>
Compound (I) 0.3% by mass
Sorbit 12.0% by mass
Sodium benzoate 0.1% by mass
Perfume 1.0% by mass
Calcium sulfate 0.5% by mass
Remainder of purified water (100% by mass)

The agent for improving liver function and the oral composition for improving liver function of this embodiment of the present invention can improve liver function, thereby: preventing, treating or treating symptoms caused by ethanol intake (for example, hangover) amelioration; prevention, treatment or amelioration of fatty liver, hepatitis such as alcoholic hepatitis and drug-induced hepatitis, liver cirrhosis, etc.;

Claims (3)

A liver function improving agent comprising a compound represented by the following formula (I) as an active ingredient.

2. The liver according to claim 1, which is used for one or more uses selected from the group consisting of promotion of hepatocyte glutathione production, promotion of hepatocyte adenosine triphosphate production, and promotion of hepatocyte proliferation. Function improver. An oral composition for improving liver function, comprising a compound represented by the following formula (I).