JP2009029735A - Prophylactic and therapeutic agent of hepatitis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new prophylactic and therapeutic agent of hepatitis. <P>SOLUTION: The prophylactic and therapeutic agent of the hepatitis contains a post-fermented tea by adding ≥110 pts.wt. of water to 100 pts.wt. of tea originated from Camellia sinensis species, expressed in terms of dry weight, and inoculating and growing filamentous fungi thereon, and having ≥2,000 units/g superoxide dismutase activity expressed in terms of solid, or an extract thereof. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  Hepatitis is an inflammatory disease of the liver classified into acute hepatitis, fulminant hepatitis, late onset hepatic failure (LOHF), chronic hepatitis, and develops due to various causes. If hepatitis is classified according to the cause, it is classified into viral hepatitis such as hepatitis A, hepatitis B and hepatitis C, alcoholic hepatitis, non-alcoholic steatohepatitis, drug hepatitis, autoimmune hepatitis and the like.

  Symptoms of hepatitis are fever, jaundice, general malaise, etc., and hepatitis C often causes cirrhosis and liver cancer through chronic hepatitis.

Examples of therapeutic agents for hepatitis include diet therapy, interferon administration, hepatoprotective drugs, steroids and the like. Recently, various reports have been made focusing on the active oxygen species scavenging activity and antioxidant activity of tea catechins. For example, the effects of tea catechin on liver cancer include an improvement effect of chronic hepatitis C by improving iron metabolism (Non-patent Document 1), and an enhancement of the antilipid oxidation effect of atherosclerosis-sensitive mouse liver (Non-patent Document 2). ), Suppression of hepatitis activity in chronic hepatitis / cirrhosis (Non-Patent Document 3), suppression of liver damage caused by alcoholic steatohepatitis (Non-Patent Document 4), growth suppression effect on human hepatoma cells (Non-Patent Document 5), etc. Has been reported. In addition, suppression of fat accumulation in the liver by catechins (Patent Document 1), prevention and treatment of excess iron-induced liver damage (Patent Document 2), remarkable reduction and improvement of liver function (Patent Document 3), etc. are known. ing.
Liver, Vol. 47 (Supplement 2), A412 (2006) J. et al. Oleo. Sci. , Vol. 54 (12), 641-648 (2005) Clinical and research, Vol. 81 (9), 1549-1552 (2004) Annual Review Gastroenterology, Vol. 2004, 332-336 (2004) Life Science Research Journal, Vol. 12, 39-47 (2003) JP 2005-179277 A JP 2003-212780 A JP 2003-26584 A

However, the preventive and therapeutic action of conventional tea catechins against hepatitis is not sufficient, and a plant-derived component having a stronger hepatitis preventive and therapeutic action has been desired.
Accordingly, an object of the present invention is to provide an agent for preventing and treating hepatitis that is derived from a plant component with high safety and has a more excellent pharmacological action.

  Accordingly, the present inventors have made various investigations focusing on post-fermented tea, and after impregnating tea with a certain amount of water and inoculating filamentous fungi, the present inventors obtained post-fermented tea with extremely high SOD activity. It was. And when hepatitis prevention treatment effect in a hepatitis model was examined using the said post-fermentation tea with the said high SOD activity, if this post-fermentation tea was administered, it discovered that a strong hepatitis prevention-treatment effect was acquired, and completed this invention. did.

  That is, the present invention provides a superoxide dismutase (Superoxide) obtained by adding 110 parts by weight or more of water to tea derived from Camellia sinensis, and inoculating and growing a fungus. The present invention provides a preventive and therapeutic agent for hepatitis containing post-fermented tea having a Dismutase) activity of 2,000 units / g or more in terms of solid content or an extract thereof.

  The effect of preventing and treating hepatitis of the post-fermented tea or its extract of the present invention is strong, and is particularly effective for nonalcoholic steatohepatitis. In addition, post-fermented tea or an extract thereof used in the present invention is highly safe and can be drunk or taken for a long period of time, and thus is particularly useful for preventing or treating transition to chronic hepatitis.

  If the tea as a raw material of post-fermentation tea used for this invention is a Camellia sinensis seed | species, it will not be specifically limited to a kind | species etc. Also, fresh tea leaves immediately after harvest, tea leaves after slaughtering, tea leaves after rough culm, tea leaves after twisting, tea leaves after mid-stitching, tea leaves after fermenting, green tea such as rough tea, tea stems, tea flowers In addition, semi-fermented tea and completely fermented tea can be used even for processed products such as powdered products, and the tea used as a raw material can be appropriately selected depending on the use of post-fermented tea. Among these, it is preferable to use non-fermented tea from the viewpoint of obtaining post-fermented tea having high SOD activity.

  The microorganism used for fermentation of these teas is preferably a filamentous fungus from the viewpoint of obtaining post-fermented tea having high SOD activity. As the filamentous fungus, it is possible to select from filamentous fungi that can be used for foods such as brewed foods and fermented foods. For example, Aspergillus genus, Eurotium genus, Rhizopus genus and the like can be used, more preferably Aspergillus oryzae, Aspergillus niger, Eurotium cristatum, Rhizopus oligosporus, etc. Can also be used. These may be used alone or in combination. These strains are available from strain distribution agencies such as IFO, IAM, ATCC, and NRRC, the Japan Brewing Association, and commercial seed strain sales companies.

  In the method for producing post-fermented tea used in the present invention, tea derived from Camellia sinensis is 110 parts by weight or more, preferably 150 parts by weight or more, more preferably 200 parts by weight or more, optimal for 100 parts by weight of tea dry weight. Add 300-400 parts by weight of water. The adjustment of the amount of water here means that water is added to tea used as a raw material so as to adjust to a condition that allows filamentous fungi to grow. For example, when crude tea is used, the crude tea already contains about 3 to 5% by weight of moisture, and the amount of moisture to be added needs to be adjusted in consideration of the moisture contained in the tea. Moreover, what contains 70 to 80 weight% of water | moisture content like fresh tea leaves does not need to be hydrated. The water content is important for obtaining the post-fermented tea having a high SOD activity according to the present invention, which is an amount capable of propagating or fermenting the filamentous fungi used for culture and fermentation. By preferentially propagating the filamentous fungus, contamination with various bacteria can be further prevented. It is preferable to add a sterilization step after the moisture adjustment. Examples of the sterilization conditions include heat sterilization at 80 to 100 ° C. for 30 to 60 minutes, or at 100 to 121 ° C. for 15 to 30 minutes. After the sterilization, the mixture is cooled, the tea is transferred to a sterilized culture / fermentor, and the following inoculation process is performed. The sterilization step is preferably performed in a closed system so that the moisture content of tea does not change.

  The tea whose moisture content has been adjusted is inoculated with filamentous fungi and is generally cultured and fermented at 20 to 40 ° C. for 3 to 30 days, preferably at 25 to 37 ° C. for 3 to 7 days. Here, the culture / fermentation method may be any method such as liquid culture / fermentation method or solid culture / fermentation method as long as it is a commonly used method. Then, it is preferable to add a sterilization process. The sterilization conditions include, for example, heat sterilization at 80 to 100 ° C. for 30 to 60 minutes, or 100 to 121 ° C. for 15 to 30 minutes, or heat drying at 80 to 120 ° C. Is sterilized, and the water content is 10% by weight or less, preferably 5% by weight or less. Thereby, the post-fermented tea with high SOD activity of the present invention is produced.

  The post-fermented tea of the present invention can be used as it is, but is sterilized by heating, dry heat, microwave, etc., and further pulverized, extracted in the form of powder, paste, or using a solvent, It can be used as a post-fermented tea extract. Furthermore, the post-fermented tea extract can be made into a post-fermented tea extract powder by drying and pulverizing the post-fermented tea extract using a spray dryer, drum dryer, freeze dryer, air dryer or the like. Moreover, it can be set as a granule using a granulator etc. as needed.

As the solvent used in the above extraction, water or alcohols having 1 to 6 carbon atoms can be used alone or a combination of two or more of these solvents can be used, and examples thereof include water, ethanol, hydrous ethanol and the like. Preferably, water alone or water-containing ethanol can be used, more preferably a mixture of water and ethanol from 0 to 95: 100 to 5 (v / v).
As extraction conditions, it is preferable to extract at about 20 to 70 ° C. for 0.1 to 5 hours, perform filtration, and further heat and cool the obtained filtrate at 80 to 95 ° C. for 30 minutes. .
The above extract is further purified by a known separation / purification method such as liquid-liquid separation, solid-liquid separation, filtration membrane, activated carbon, adsorption resin, ion exchange resin, etc., in order to remove inert impurities as appropriate. May be. Specifically, the extract powder may be extracted again using the extraction solvent.

  The post-fermented tea or extract thereof obtained by the above production method has an SOD activity that is one index of the antioxidant activity of 2,000 units or more, preferably 8,000 units or more, per 1 g of post-fermented tea solid content. Preferably, it has 9,000 units or more, more preferably 9,000 to 500,000 units. For example, post-fermented tea produced by the production method of the present invention using Aspergillus oryzae as green tea as a raw material has SOD activity of 9,000 units or more per 1 g of post-fermented tea solid content.

  The post-fermented tea or its extract having excellent SOD activity is superior to a non-alcoholic steatohepatitis (NASH) model, which is one of the hepatitis models, as shown in the examples below. Has preventive and therapeutic effects. Specifically, the aspartate aminotransferase (AST) value, the alanine aminotransferase (ALT) value, and the hyaluronic acid value, which are indicators of hepatitis, were significantly recovered. Moreover, the production amount of reactive oxygen species (ROS: Reactive Oxygen Species) derived from liver mitochondria was reduced. Furthermore, it has the effect of improving the pathological tissue of the liver. Therefore, the post-fermented tea or its extract is useful as a preventive and therapeutic agent for various hepatitis such as acute hepatitis, chronic hepatitis, various viral hepatitis, non-alcoholic steatohepatitis and the like.

  The hepatitis preventive / therapeutic agent of the present invention can be used as a pharmaceutical, food for specified health use, functional food or the like. Examples of the administration form of these drugs include oral, injection, and external use, and the oral administration form is preferred. As forms of oral medicines and foods, in addition to ampoules, capsules, pills, tablets, powders, granules, solids, liquids, gels, bubbles, etc., they can be blended in various foods. In preparing these compositions, excipients, binders, lubricants, and the like can be appropriately blended. The blending amount of the post-fermented tea or the extract thereof in these medicines and foods is preferably 0.0001 to 20% by weight, particularly 0.01 to 10% by weight, particularly 0.01 ~ 5 wt% is preferred.

  The dose of the hepatitis preventive and therapeutic agent of the present invention is not particularly limited, but as a solid content (dry weight) of post-fermented tea or its extract per day for adults, 10 to 5,000 mg, further 50 to 1,000 mg, 100 to 500 mg is particularly preferable, and these amounts may be administered once or divided into several times.

  Hereinafter, the present invention will be described in more detail and specifically with reference to examples, but the present invention is not limited to the following examples.

[Reference Example 1]
0, 50, 70, 80, 100, 200, 300, 350, 400, and 500 parts by weight of 500 g of green tea (raw tea). And 700 parts by weight of water were added and mixed, and then heat-sterilized at 80 ° C. for 60 minutes in a closed system. After cooling to 30 ° C., the green tea leaves were transferred to a previously sterilized culture / fermentor, deposited to a thickness of 5 cm, and inoculated with Aspergillus oryzae IFO5238. After inoculation, the cells were cultured at 30 ° C. for 7 days and then dried to obtain post-fermented tea. After that, 5,000 mL of 50% (volume / volume) ethanol was added to the fermented tea, followed by extraction with stirring. The filtrate obtained by solid-liquid separation by filtration was concentrated to a solid content of 30% (weight / volume), heated at 80 ° C. for 30 minutes and cooled to obtain a post-fermented tea extract. With respect to the post-fermented tea extract, SOD activity was measured using SOD Assay Kit-WST (manufactured by Dojin Chemical Co., Ltd.) and converted to the amount of post-fermented tea solids. The results are shown in Table 1.

The measurement of SOD activity was performed as follows. First, a post-fermented tea extract serving as a sample was diluted with distilled water, and sample solutions were prepared to be 0.075 mg / mL, 0.0375 mg / mL, 0.0075 mg / mL, and 0.00375 mg / mL. . 20 μL of this sample solution was dispensed into each well of a 96-well plate. Next, 200 μL of WST working solution prepared in accordance with Technical Information enclosed in SOD Assay Kit-WST was added and mixed well. Furthermore, 20 μL of Enzyme working solution adjusted according to Technical Information attached to SOD Assay Kit-WST was added by 20 μL each with a multi-channel pipette, incubated at 37 ° C. for 20 minutes in a plate reader, and the absorbance was measured at a wavelength of 450 nm. In each case, a blank using an attached dilution buffer was provided instead of the enzyme working solution. Further, a control using distilled water instead of the sample solution and its blank were provided. From the measured absorbance, the inhibition rate of the reaction in which “WST-1 formatzan” was generated from “superoxide” and “WST-1” was determined, and the IC ₅₀ value (unit: g / mL) of the sample was calculated.
In addition, a standard curve was prepared using a function of SOD concentration and inhibition rate, using an SOD standard product instead of the sample solution. An IC ₅₀ value (unit: units / mL) of SOD was calculated from the prepared calibration curve.
It was calculated SOD activity of the sample from the "IC ₅₀ value of the sample" and "IC ₅₀ value of SOD" above. The calculation formula is as follows.
(Sample SOD activity units: units / g) = (IC 50 values of SOD) ÷ (IC ₅₀ value of the sample)

  From Table 1, it can be seen that a high SOD activity is exhibited in the range of 200 to 500 parts by weight of water addition, and a higher SOD activity is exhibited in the range of 300 to 400 parts by weight.

  Moreover, when the obtained fermented tea extract was applied to the skin, there was almost no irritation. Also, the taste was good with low astringency.

  Moreover, the result of having measured the SOD activity of the post-fermented tea conventionally drunk by the same method is shown in Table 2.

  From Table 2, it can be seen that the post-fermented tea of the present invention has a higher SOD activity than the conventional post-fermented tea.

[Reference Example 2]
1,750 mL of water was added to 500 g of green tea (raw tea) and mixed, and then heat-sterilized at 80 ° C. for 60 minutes in a closed system. After cooling to 30 ° C., the green tea was transferred to a previously sterilized culture / fermentor, deposited to a thickness of 4 cm, and Aspergillus oryzae IFO5238 was inoculated. After inoculation, the cells were cultured and fermented at 30 ° C. for 7 days. After completion of the culture and fermentation, the mixture was dried with a blow dryer to obtain 486 g of post-fermented tea of the present invention. Next, 5,000 mL of water was added to the post-fermented tea, and stirring extraction was performed at 50 ° C. for 1 hour. The filtrate obtained by solid-liquid separation by filtration was concentrated to a solid content of 30%, heat-treated at 80 ° C. for 30 minutes and cooled to obtain a post-fermented tea water extract. The obtained post-fermented tea water extract was dried with a freeze dryer to obtain a post-fermented tea water extract powder (108 g). As a result of measuring the SOD activity using the SOD Assay Kit-WST for the obtained post-fermented tea water extract powder, 20,062 units (80,238 units per gram of post-fermented tea water extract powder) per 1 g of the post-fermented tea solid content. there were. The obtained extract powder was good with no astringency, no bitterness and no skin irritation.

[Example 1]
NASH having biochemical and histopathological characteristics of NASH by applying oxidative stress (OS: Oxgen Stress) to an experimentally-adjusted fatty liver-bearing rat to form an in vivo hypoxic state Although pathological model rats can be produced, at the same time as oxidative stress is applied to fatty liver-bearing rats, post-fermented tea water extract is administered, then blood biochemical examination of the rats, ESR (Electron Spin of the amount of ROS in liver mitochondria) The preventive effect of the post-fermented tea water extract on the progression of the disease state from fatty liver to NASH was evaluated by performing quantitative determination by the Resonance method and histological observation of the liver tissue.

(1) Implementation method 6-week-old Wistar male rats (180-200 g / animal) were used as experimental animals. Two to three animals were raised in polypropylene opaque cages (W220 × L320 × H135, manufactured by Natsume Seisakusho). The breeding room was maintained at a humidity of 40 to 50% and a room temperature of 20 to 25 ° C., and was set to a 12 hour light / dark cycle (lit; AM 8:00, extinguished; PM 8:00).

For the preparation of fatty liver, a choline-deficient diet (CDHF: Choline Defensive High-Fat Food, manufactured by Oriental Yeast Co., Ltd.) was given by free intake for 4 weeks. Thereafter, CDHF was given until the end of the experiment in order to maintain the disease state.
In order to create an in vivo hypoxic state by loading OS and create a NASH disease state, 30 mg / kg (body weight) / day of sodium nitrite dissolved in physiological saline was applied to the above fatty liver-bearing rats for 6 weeks. Administered intraperitoneally. During the administration period, blood was collected from the tail vein every two weeks to confirm the pathological condition, and confirmed that there was no problem in the progress of the pathological condition.

  In order to evaluate the effectiveness of post-fermented tea water extract against NASH, 10 mg / kg (body weight) / day of post-fermented tea water extract (obtained in Reference Example 2) at the same time for the sodium nitrite administration group, or 200 mg / kg (body weight) / day was administered by oral gavage with a sonde for 6 weeks. After completion of the administration period, the rats were sacrificed, the blood biochemical examination of the rats and the ROS in liver mitochondria were quantified, and the histopathological changes in the liver tissue were observed.

  This experiment was divided into groups (i) group (CDHF + OS), (ii) group (CDHF + OS + tea 10 mg / kg), and (iii) group (CDHF + OS + tea 200 mg / kg), and each group had 6 animals (n = 6). ).

  Plasma AST and ALT values were measured with transaminase CII-Test Wako (Wako Pure Chemical Industries, Ltd.). Plasma hyaluronic acid levels were measured with a hyaluronic acid measurement kit (Seikagaku Corporation).

  The liver mitochondrial ROS amount was measured according to the following procedure. That is, a liver sample was collected from the inferior vena cava after perfusion with a 1.15% potassium chloride solution (containing 5 mM benzamidine). 3 mL of Tris-HCl buffer (pH 7.4, 0.25 M sucrose, 0.1 M potassium chloride included) is added to 1 g of liver tissue, homogenized, and then centrifuged at 3,000 × g (10 minutes, 4 ° C.). Separated to obtain a supernatant. The supernatant is then centrifuged at 9,000 × g (20 minutes, 4 ° C.), and the precipitate is added with 1 mL of Tris-HCl buffer (pH 7.4, containing 0.25 M sucrose, 0.1 M potassium chloride). The mitochondrial fraction was obtained by centrifugal washing twice. To 14.28 mg of this fraction, 1 mL of Tris-HCl buffer (pH 7.4, containing 0.25 M sucrose, 0.1 M potassium chloride) was added and dissolved to obtain a sample solution. The concentration at this time corresponds to 500 μg / mL in terms of mitochondrial protein.

35 μl of the above sample solution, 25 μl of a solution containing 0.1% dodecyl maltoside, 5 mM glutamate, 5 mM malate and 200 mM succinate, 4.6 μl, 5,5-dimethyl-1-oxyline (DMPO) solution 20 μl and 2 mM NADH solution A total of 100 μl of 20 μl was incubated at 37 ° C. for 5 minutes, and immediately thereafter, the ROS amount of this solution was measured at room temperature using an ESR measuring device (JES-REIX / HR, manufactured by JEOL Ltd.). In the measurement, Mn ²⁺ of MnO previously inserted in the cavity was used as a radical calculation standard. The amount of radicals generated was calculated by the ratio of the Mn ²⁺ maximum meter definition (hr) to that of the mitochondrial sample (hs), that is, ESR intensity (hs / hr).

  As a statistical treatment, all results are expressed as mean ± standard error. The obtained data were subjected to statistical processing using one-way analysis of variance (ANOVA) followed by Turkey's multiple comparison test. For comparison between the two groups, Students t-test was used, and a risk rate of 5% or less was determined to be superior.

(2) Experimental results The results of sacrificing the rats after the administration period and observing the biochemical examination of the blood of the rats, the amount of ROS in the liver mitochondria, and the histopathological changes of the liver tissues are shown below.

(2) -1 Biochemical test (i) group (CDHF + OS)
1) Plasma AST value (units / mL) increased from 25 ± 2 IU / L to 220 ± 38 IU / L.
2) Plasma ALT value (units / mL) increased from 21 ± 2 IU / L to 47 ± 2 IU / L.
3) Plasma hyaluronic acid level (mg / mL) increased from 95 ± 12 mg / mL to 205 ± 27 mg / mL.
From this result, it was clearly recognized that the fatty liver progressed to NASH due to oxidative stress.

(Ii) group (CDHF + OS + tea 10 mg / kg)
1) Plasma AST value (units / mL) increased from 21 ± 2 IU / L to 157 ± 2 IU / L.
2) Plasma ALT value (units / mL) increased from 22 ± 2 IU / L to 35 ± 2 IU / L.
3) Plasma hyaluronic acid level (mg / mL) increased from 119 ± 14 mg / mL to 184 ± 15 mg / mL.
From this result, it was confirmed that the progression from fatty liver to NASH induced by oxidative stress was improved by administration of post-fermented tea water extract powder 10 mg / kg (body weight).

(Iii) group (CDHF + OS + tea 200 mg / kg)
1) Plasma AST value (units / mL) increased from 21 ± 3 IU / L to 88 ± 9 IU / L.
2) Plasma ALT value (units / mL) increased from 22 ± 2 IU / L to 28 ± 2 IU / L (recovered to normal value).
3) Plasma hyaluronic acid level (mg / mL) decreased from 119 ± 15 mg / mL to 102 ± 11 mg / mL (recovered to normal level).
From these results, it was confirmed that the progression from fatty liver to NASH induced by oxidative stress was greatly improved by administration of post-fermented tea water extract powder 200 mg / kg (body weight).

(2) -2 Liver mitochondria-derived ROS production value (signal relative intensity)
For signal relative intensity 0.7 ± 0.1 before OS loading,
(I) Group (CDHF + OS): 1.0 ± 0.1
(Ii) Group (CDHF + OS + tea 10 mg / kg): 0.8 ± 0.1
(Iii) group (CDHF + OS + tea 200 mg / kg): 0.5 ± 0.1
Met.
From these results, it was recognized that the amount of liver mitochondrial-derived ROS production that increases with the progress of NASH tended to decrease in a concentration-dependent manner by administration of post-fermented tea water extract powder.

(2) -3 Observation of liver tissue by hematoxylin and eosin staining To confirm histopathological changes in liver tissue, hematoxylin and eosin staining (HE staining) is performed based on a known technique, and the state of large droplet fat deposition is confirmed. Observed, the following results were obtained.
(I) Group (CDHF + OS)
There are many large droplets and large hepatocyte disorder.
(Ii) group (CDHF + OS + tea 10 mg / kg)
Medium large droplets and moderate disturbance of hepatocyte array.
(Iii) group (CDHF + OS + tea 200 mg / kg)
There are small large lipid droplets and small disturbance of hepatocyte arrangement.
From these results, it was recognized that the increase in large lipid droplets and the increase in disorder of hepatocyte arrangement in the liver tissue, which increase with the progress of NASH, were suppressed in a concentration-dependent manner by the post-fermented tea water extract administration. .

(2) -4 Observation of liver tissue by Masson / Trichrome staining To confirm histopathological changes in liver tissue, Masson / Trichrome staining was performed based on a known method, and the fibrosis state of collagen fibers was observed. The following results were obtained.
(I) Group (CDHF + OS)
The formation of bridges from the portal vein region to the central vein region was observed, and pseudolobular formation was observed.
(Ii) group (CDHF + OS + tea 10 mg / kg)
Mild portal vein to central vein bridge formation was observed.
(Iii) group (CDHF + OS + tea 200 mg / kg)
Fibrosis is observed around the portal vein and central vein, but no cross-linking is observed.
From these results, it was recognized that the increase in cross-linking and fibrosis in the liver tissue, which increases with progression from fatty liver to NASH, was suppressed in a concentration-dependent manner by the post-fermented tea water extract administration.

(2) -5 Observation of liver tissue by Berlin Blue staining In order to confirm the histopathological changes of liver tissue, Berlin Blue staining was performed based on a known method, and the iron ion deposition state was observed. Obtained.
(I) Group (CDHF + OS)
Large iron deposits were observed from the portal vein area to the central vein area.
(Ii) group (CDHF + OS + tea 10 mg / kg)
Mild iron deposition was observed from the portal vein area to the central vein area.
(Iii) group (CDHF + OS + tea 200 mg / kg)
Little iron deposition was observed.
From these results, it was recognized that the increase in iron deposition in the liver tissue, which increases with progression from fatty liver to NASH, was suppressed in a concentration-dependent manner by the post-fermented tea water extract administration.

[Formulation Example 1]
Granules were produced according to the following formulation.
Post-fermented tea extract powder (Reference Example 2) 350 (parts by mass)
Lactose 470
Crystalline cellulose 150
Hydroxypropyl cellulose 30

[Formulation Example 2]
According to the following formulation, wet granulation was performed and tablets were obtained by tableting.
Post-fermented tea extract powder (Reference Example 2) 350 (parts by mass)
Lactose 470
Crystalline cellulose 140
Hydroxypropyl cellulose 30
Magnesium stearate 1
Talc 9

Claims (4)

  Superoxide dismutase activity obtained by adding 110 parts by weight or more of water to tea derived from Camellia sinensis seeds with respect to 100 parts by weight of dry tea, inoculating filamentous fungi, and growing the solids. A hepatitis preventive / therapeutic agent containing post-fermented tea or an extract thereof having 2,000 units / g or more in terms of conversion.   The hepatitis preventive or therapeutic agent according to claim 1, wherein the hepatitis is acute hepatitis or chronic hepatitis.   The hepatitis preventive or therapeutic agent according to claim 1, wherein the hepatitis is chronic hepatitis.   The hepatitis preventive or therapeutic agent according to claim 1, wherein the hepatitis is non-alcoholic steatohepatitis.