Liver function improver and liver function-improving oral composition

Abstract

To discover, among compounds derived from natural products, those having excellent action regarding liver function-improving action, and to provide liver function improvers containing them as active ingredients.SOLUTION: A liver function improver used for liver function-improving application based on hepatocellular adenosine triphosphate production-promoting action, comprising as an active ingredient a compound represented by the following formula (I), and a liver function-improving oral composition used for liver function-improving application based on hepatocellular adenosine triphosphate production-promoting action, containing a compound represented by the following formula (I).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an agent for improving liver function, which 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, which contains the compound. [Background technology]

[0002] 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, detoxification of harmful substances, bile production, and blood storage. Although liver damage is difficult to detect, liver dysfunction caused by alcohol consumption, overnutrition, drug abuse, hepatitis viruses, etc. can lead to 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 crucial for maintaining a healthy lifestyle.

[0003] Glutathione is known to be a biological component that protects the liver. Glutathione is a tripeptide composed of three amino acids, glutamic acid, cysteine, and glycine, and is a compound containing the major 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 reactions, and acting as an SH donor for various enzymes. In particular, glutathione is known to be involved in the detoxification mechanism and protect liver function. Hepatic glutathione is consumed in large quantities during the metabolism of ethanol after drinking alcohol and the metabolism and detoxification of drugs. Decreased hepatic glutathione levels can lead to liver dysfunction, including acute and chronic alcoholic hepatitis and drug-induced hepatitis. Systemic glutathione levels can also lead to a variety of symptoms, including cataracts, Parkinson's disease, and skin pigmentation.

[0004] Therefore, if glutathione production in the liver (hepatocytes) can be promoted, liver function can be improved, and various disorders caused by a decrease in glutathione can be prevented, treated, or improved. Liquiritin (see Patent Document 1) and the like are known to have the effect of promoting glutathione production in hepatocytes.

[0005] Adenosine triphosphate (ATP) is known to improve liver function. ATP is produced through the metabolism of glucose and fat and is used as an energy source. The liver uses ATP as an energy source for many chemical reactions, including the metabolism and detoxification of ethanol and drugs. A decrease in ATP production is thought to reduce the efficiency of these reactions, as well as to result in a lack of energy for activities such as labor and exercise, leading to fatigue. Therefore, if ATP production in the liver can be promoted, it is thought that it will be possible to prevent or improve various symptoms caused by ethanol intake (e.g., hangover, etc.), prevent, treat, or improve 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.

[0006] 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 where liver dysfunction persists, such as fatty liver, chronic hepatitis, and cirrhosis. Therefore, if the proliferation of hepatocytes can be efficiently promoted, it is thought that this will lead to the treatment and improvement of liver dysfunction. Pyroglutamic acid and a combination of aspartic acid and glutamic acid (see Patent Document 3) are known to have the effect of promoting hepatocyte proliferation. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2009-269889 [Patent Document 2] Japanese Patent Application Laid-Open No. 2011-184381 [Patent Document 3] International Publication No. 2014 / 208381 Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is 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. [Means for solving the problem]

[0009] 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. Also, the oral composition for improving liver function of the present invention is characterized by incorporating a compound represented by the following formula (I).

[0010] [ka] [Effects of the Invention]

[0011] According to the present invention, by using the compound represented by the above formula (I) as an active ingredient, it is possible to provide an agent for improving liver function having an effective action. Furthermore, by incorporating the compound represented by the above formula (I), it is possible to provide an oral composition suitable for improving liver function. DETAILED DESCRIPTION OF THE INVENTION

[0012] Hereinafter, an embodiment of the present invention will be described.

[0013] [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).

[0014] [ka]

[0015] The compound represented by the formula (I) is a cinnamic acid derivative also known as 3-(4-hydroxy-3-methoxyphenyl)propionic acid. Hereinafter, in this specification, the compound represented by the formula (I) may be referred to as compound (I).

[0016] 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, soybean, adzuki bean, corn, etc.

[0017] Compound (I) can also be produced by, for example, fermenting 3-(4-hydroxy-3-methoxyphenyl)propenoic acid or a derivative thereof, or a composition containing the same (e.g., a crushed plant material or extract, etc.) with a microorganism having a phenolic acid reductase to convert the 3-(4-hydroxy-3-methoxyphenyl)propenoic acid to Compound (I), followed by extracting, isolating, and purifying the resulting fermented product. Examples of compositions containing 3-(4-hydroxy-3-methoxyphenyl)propenoic acid include crushed materials and extracts of 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 the same may 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.

[0018] 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 a conventional method. 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 pulverization using a crusher. Drying can be carried out in the sun or using a commonly used dryer. Furthermore, the plant or fermented product may be subjected to pretreatment such as degreasing with a nonpolar solvent such as hexane before use as the extraction raw material. By carrying out pretreatment such as degreasing, extraction with a polar solvent can be carried out efficiently.

[0019] As the extraction solvent, it is preferable to use a polar solvent, such as water or a hydrophilic organic solvent, which is preferably used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent.

[0020] 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, physiological saline, phosphate buffer, phosphate-buffered physiological saline, etc.

[0021] Examples of 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; polyhydric alcohols having 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.

[0022] When a mixture of two or more polar solvents is used as an extraction solvent, the mixture ratio can be any and can be adjusted appropriately. For example, when a mixture of water and a hydrophilic organic solvent is used as an extraction solvent, the mixture can 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.

[0023] The extraction process is not particularly limited as long as it can dissolve the soluble components contained in the extraction raw material into 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, followed by filtration to remove the extraction residue, to obtain an extract. The solvent is distilled off from the obtained extract to obtain a paste-like concentrate, which is then further dried to obtain a dried product.

[0024] 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 by 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 appropriately selected 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 reversed-phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, or column chromatography using an ion-exchange resin.

[0025] [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.

[0026] Here, the liver function improving effect of Compound (I) is preferably exerted based on the promoting effect of glutathione production in hepatocytes, the promoting effect of adenosine triphosphate (ATP) production in hepatocytes, or the promoting effect of hepatocyte proliferation, but is not limited to the liver function improving effect exerted based on the above-mentioned effects.

[0027] Furthermore, compound (I) can be used to promote glutathione production in hepatocytes, promote ATP production in hepatocytes, or promote hepatocyte proliferation, utilizing its hepatocyte glutathione production promoting effect, hepatocyte ATP production promoting effect, or hepatocyte proliferation promoting effect, respectively. That is, the liver function improver of this embodiment can also be used as a hepatocyte glutathione production promoter, a hepatocyte ATP production promoter, or a hepatocyte proliferation promoter, containing compound (I) as an active ingredient.

[0028] Note that, instead of isolated Compound (I), a composition containing Compound (I) may be used as the active ingredient of the liver function improver according to this embodiment. Here, the "composition containing Compound (I)" in this embodiment includes an extract obtained using a plant containing Compound (I) as an extraction raw material, a fermented product containing Compound (I), and an extract obtained using the fermented product as an extraction raw material. Furthermore, the "extract" includes an extract obtained by extraction treatment, a diluted or concentrated solution of the extract, or a dried product obtained by drying the extract.

[0029] 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 an increased purity as the active ingredient, a liver function improver with even more excellent effects can be obtained.

[0030] 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).

[0031] 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 a conventional method. In this case, examples of auxiliary agents that can be used include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring and odor-correcting agents. The liver function improver can be incorporated into other compositions (e.g., oral compositions, as described below) and used, or can be used as an external liquid preparation, patch, or the like.

[0032] 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.

[0033] In addition, if necessary, the liver function improver of this embodiment can be used as an active ingredient by blending other natural extracts, etc. that have liver function improving effects with compound (I) or a composition containing compound (I).

[0034] The method of administering the liver function improver of this embodiment to a patient may include oral administration, intraperitoneal administration, intravenous administration, subcutaneous administration, etc., and a method suitable for the prevention or treatment of the disease may be appropriately selected depending on the type of disease. The dosage of the liver function improver of this embodiment may also be appropriately increased or decreased depending on the type and severity of the disease, individual differences between patients, the administration method, the administration period, etc.

[0035] 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.

[0036] 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 glutathione concentrations in the body, such as cataracts and Parkinson's disease, through the hepatocyte glutathione production promoting effect of compound (I).

[0037] Furthermore, the liver function improver of this embodiment or the aforementioned hepatocyte ATP production promoter can be used for purposes such as relieving fatigue and lethargy through the hepatocyte ATP production promoting action of compound (I).

[0038] 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 effect of Compound (I).

[0039] Furthermore, since the liver function improver of this embodiment has an excellent effect in improving liver function, it can also be suitably used as a reagent for research into the mechanisms of these actions.

[0040] [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.

[0041] 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 obtained. The above-mentioned action is preferable because the effect is easily exerted by imparting it to an oral composition.

[0042] Here, oral compositions refer to compositions that are unlikely to be harmful to human health and that are taken orally or by administration through the gastrointestinal tract in normal social life, and are not limited to administrative classifications such as foods, medicines, or quasi-drugs. Therefore, the "oral composition" in this embodiment broadly includes orally taken general foods, feeds, health foods, health functional foods (foods for specified health uses, foods with nutrient functions, and foods and beverages with functional claims), quasi-drugs, medicines, and the like. The oral composition according to this embodiment is preferably an oral composition that can display the favorable effects of Compound (I) on the oral composition or its packaging, and is particularly preferably a health functional food (foods for specified health uses, foods with functional claims, foods with nutrient functions), quasi-drugs, or medicines.

[0043] 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 appropriately adjusted taking into account the intended use, symptoms, gender, etc. However, taking into account the general intake of the oral composition to be added, it is preferable to adjust the amount of compound (I) so that the daily intake per adult is about 1 to 1000 mg. Note that when the oral composition 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 usually 0.1 to 100% by mass, preferably 5 to 100% by mass, of the oral composition to be added.

[0044] The oral composition of this embodiment may be a composition in which compound (I) is incorporated into any oral composition that does not interfere with its activity, or may be a nutritional supplement containing compound (I) as a main ingredient.

[0045] When producing the oral composition of this embodiment, any auxiliary agent can be added, 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; and fats and oils such as soybean oil and medium-chain fatty acid triglycerides, to form an oral composition in any shape.

[0046] Oral compositions that can be formulated with compound (I) are not particularly limited, and specific examples thereof 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; confectioneries such as candy, chewing gum, candy, chewing gum, chocolate, tablet candy, snacks, biscuits, jellies, jams, creams, and baked goods; Examples of such oral compositions 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 oil-based 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 be used in combination.

[0047] Although the liver function improver and oral composition for improving liver function of this embodiment are suitable for use in humans, they 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 effects are achieved. [Example]

[0048] The present invention will be specifically described below by showing 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.

[0049] [Test Example 1] Test of glutathione production promoting effect in hepatocytes Compound (I) (Sample 1) was tested for its glutathione production promoting activity in hepatocytes as follows.

[0050] Normal human hepatocytes (hepatocytes) were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% FBS, and then harvested by trypsinization. The harvested cells were collected at a concentration of 1.0 × 10 5 The cells were diluted with 10% FBS-containing DMEM to a cell density of 100 cells / mL, and then seeded in a 48-well plate at 200 μL per well and cultured overnight.

[0051] 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 the cells were further incubated for 24 hours. As a control, cells were incubated in the same manner using 1% FBS-containing DMEM without sample. After incubation, the medium was removed from each well, and the cells were washed with 400 μL of PBS(-). The cells were then lysed using 150 μL of M-PER (Pierce).

[0052] 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. 25 μL of 10 mmol / L 5,5'-dithiobis(2-nitrobenzoic acid) was then added. The absorbance at 412 nm was measured for 5 minutes, and ΔOD / min was calculated. Total glutathione concentrations were calculated based on a calibration curve prepared using oxidized glutathione (Fujifilm Wako Pure Chemical Industries, Ltd.). The values ​​obtained were corrected for the amount of glutathione per total protein, and the glutathione production promotion rate (%) was calculated using the following formula:

[0053] Glutathione production promotion rate (%) = B / A x 100 The terms in the formula represent the following: A: Amount of glutathione per total protein in cells without sample added B: Amount of glutathione per total protein in cells to which the test sample was added The results are shown in Table 1.

[0054] [Table 1]

[0055] As shown in Table 1, compound (I) (sample 1) was found to have an excellent effect of promoting glutathione production in hepatocytes.

[0056] [Test Example 2] Test of ATP production promotion in hepatocytes Compound (I) (Sample 1) was tested for its ATP production promoting effect in hepatocytes as follows.

[0057] Normal human hepatocytes (hepatocytes) were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% FBS, and then harvested by trypsinization. The harvested cells were collected at a concentration of 2.0 × 105 The cells were diluted with 10% FBS-containing DMEM to a cell density of 100 μL / mL, and then seeded in a 96-well plate at 100 μL per well and cultured overnight.

[0058] After incubation, the medium was removed, and 100 μL of the test sample (Sample 1, final concentration see Table 2 below) dissolved in 10% FBS-containing DMEM was added to each well and incubated for 2 hours. As a control, the cells were incubated in the same manner using 10% FBS-containing DMEM without the sample.

[0059] 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 obtained results, the ATP production promotion rate (%) was calculated using the following formula:

[0060] ATP production promotion rate (%)=A / B×100 The terms in the formula represent the following: A: Amount of chemiluminescence in cells to which the test sample was added B: Chemiluminescence intensity in cells without sample added The results are shown in Table 2.

[0061] [Table 2]

[0062] As shown in Table 2, compound (I) (sample 1) was found to have an excellent ATP production promoting effect in hepatocytes.

[0063] [Test Example 3] Liver cell proliferation promotion test Compound (I) (sample 1) was tested for its hepatocyte proliferation promoting activity as follows.

[0064] Normal human hepatocytes were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% FBS, and then harvested by trypsinization. The harvested cells were collected at a concentration of 1.25 × 10 4 The cells were diluted with 1% FBS-containing DMEM to a cell density of 100 cells / mL, and then seeded at 100 μL per well in a 96-well plate and cultured overnight.

[0065] After incubation, the medium was removed, and 200 μL of the test sample (Sample 1, final concentration see Table 3 below) dissolved in 1% FBS-containing DMEM was added to each well and incubated for an additional 3 days. As a control, cells were incubated in the same manner using 1% FBS-containing DMEM without the sample.

[0066] After incubation, the hepatocyte proliferation-promoting activity was measured by 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 another 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 calculate the amount of blue formazan produced. From the measurement results, the hepatocyte proliferation promotion rate (%) was calculated using the following formula:

[0067] 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 the test sample was added B: Amount of blue formazan produced in cells without sample addition The results are shown in Table 3.

[0068] [Table 3]

[0069] As shown in Table 3, Compound (I) (Sample 1) was found to have an excellent hepatocyte proliferation promoting effect.

[0070] [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) 83.4mg Casein phosphopeptide 16.7mg Vitamin C 33.4mg Maltitol 136.8mg Collagen 12.7mg Sucrose fatty acid ester 12.0mg

[0071] [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 10.0mg Hydroxypropyl cellulose (HPC-L) 10.0 mg

[0072] [Formulation example 3] An oral liquid preparation having the following composition was prepared by a conventional method. <Composition in 1 ampoule (100 mL)> 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) [Industrial Applicability]

[0073] 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., hangover); the prevention, treatment, or amelioration of fatty liver, hepatitis such as alcoholic hepatitis and drug-induced hepatitis, cirrhosis, etc.

Claims

1. The compound represented by the following formula (I) is used as an active ingredient: Used to improve liver function by promoting adenosine triphosphate production in hepatocytes A liver function improver characterized by: 【Chemical 1】

2. A compound represented by the following formula (I) is blended, Used to improve liver function by promoting adenosine triphosphate production in hepatocytes An oral composition for improving liver function, characterized by: 【Chemistry 2】

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