JP2008260695A - Hepatopathy inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a hepatopathy inhibitor having excellent inhibitory action on hepatopathy, especially one against alcoholic hepatopathy, nonalcoholic hepatopathy, hepatitis C and hepatic cirrhosis C. <P>SOLUTION: The hepatopathy inhibitor comprises a dried fruit body of Antrodia camphorata, its extract or mycelium. The hepatopathy inhibitor comprises the dried fruit body of Antrodia camphorata, its extract or mycelium and interferon. The hepatopathy is alcoholic hepatopathy, nonalcoholic hepatopathy, hepatitis C or hepatic cirrhosis C. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to a hepatic disorder inhibitor containing a dried fruit of Benix nokitake (Taiwan name: Ashishiba) fruit body, an extract thereof or mycelium, and a hepatic disorder inhibitor combined with interferon.
In detail, it is alcoholic liver disorder, non-alcoholic steatohepatitis, hepatitis C or C liver cirrhosis containing a dried product of the fruit body of Benix nokitake (Taiwan name: Kajiba), its extract or mycelium The present invention relates to an inhibitor of liver injury and an inhibitor of liver injury which is alcoholic liver injury, non-alcoholic steatohepatitis, hepatitis C or cirrhosis C using this and interferon in combination.

Benicus mushroom is considered to be a perennial plant of the genus Antrodia which is also referred to as cow ginger or gyucho lawn.
Benicus mushroom is a Taiwan-specific fungus that lives only in Taiwan in the world. It is a bright red color that is parasitized by a 100-year-old deep mountain from 1000 to 1500 meters above sea level and that has a hollow part. To brown cocoon.

  Benix nokitake has long been prized as a folklore medicine in Taiwan, but its active ingredients have been analyzed, and so far, β-glucan, triterpenes, γ-aminobutyric acid, ergosterol, etc. Ingredients are found.

  It is an object of the present invention to provide a liver disorder inhibitor having an excellent liver disorder-inhibiting action, and particularly an effective liver disorder inhibitor for alcoholic liver disorder, non-alcoholic steatohepatitis, hepatitis C and cirrhosis C. .

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a dried product, an extract or a mycelium of Benix nokitake (Taiwan name: Yashiba) fruit body has excellent liver damage suppression. In particular, it is effective for alcoholic liver disorders, non-alcoholic steatohepatitis, hepatitis C and cirrhosis of cigarettes, and dried fruit of Benix nokitake (Taiwan name: Yashiba) fruit body, extract thereof Or, when mycelium and interferon are used in combination, the present invention has been found by exhibiting a further excellent liver injury-suppressing action, particularly having a remarkable effect on hepatitis C.

That is, the present invention
1. Benix nokitake (Taiwan name: Ashiba) fruit body dried product, extract thereof or liver damage inhibitor containing mycelium,
2. The above-mentioned 1. using interferon together. The liver disorder inhibitor described,
3. 1. The liver disorder is alcoholic liver disorder. Or 2. The liver disorder inhibitor described,
4). 1. The liver disorder is nonalcoholic steatohepatitis. Or 2. The liver disorder inhibitor described,
5. 1. The liver disorder is hepatitis C. Or 2. The liver disorder inhibitor described,
6). 1. The liver disorder is type C cirrhosis. Or 2. The liver disorder inhibitor described,
It is about.

The hepatic disorder inhibitor of the present invention has an excellent inhibitory effect on alcoholic liver disorder, nonalcoholic steatohepatitis, hepatitis C and liver cirrhosis such as C cirrhosis, and further suppresses liver disorder combined with interferon Since the agent has a remarkable effect on hepatitis C, it can be used as a pharmaceutical or a food or drink.

The present invention will be described in further detail.
The present invention relates to a liver disorder inhibitor containing a dried fruit of Benix nokitake (Taiwan name: Ashishiba) fruit body, an extract thereof, or a mycelium.
Benix nokitake can be obtained as a natural product (natural product), but can also be produced by mycelium culture or cultivation.
The dried material of Benicus mushroom can be used in any form such as powder, granule, tableting, capsule and the like.
As the extract of Benicus mushroom, a method used as a general method for extracting mushrooms can be used.
Specific extraction methods include extraction with hot water, extraction with alcohol (ethanol), extraction with water-ethanol (for example, 50% ethanol solution), and the like.

The dried material of the above-mentioned Benix nokitake (Taiwan name: Ashishiba) fruit body, its extract or mycelium is used for various liver disorders such as alcoholic hepatitis, nonalcoholic steatohepatitis, viral hepatitis, type A It is useful as an inhibitor for hepatitis, hepatitis B, hepatitis C, and cirrhosis C, and is particularly useful as an inhibitor for alcoholic hepatitis, non-alcoholic steatohepatitis, hepatitis C, and cirrhosis C.
Therefore, the dried product of the fruit body of Benix nokitake (Taiwan name: Anemone), its extract or mycelium can be used directly for applications such as pharmaceuticals and foods and drinks.

  When using the above-mentioned dried body of Benix nokitake (Taiwan name: Ashishiba) fruit body, its extract or mycelium as a food or drink, it is preferably implemented as a health food having a liver damage-inhibiting action. Specifically, the product may be mixed with various components such as known sweeteners, acidulants, vitamins, etc. to meet the user's preference. For example, it can be provided in the form of dairy products such as tablets, capsules, drinks, yogurt, seasonings, processed foods, desserts, confectionery and the like.

  Furthermore, it can be widely applied to various foods and drinks such as retort foods, canned foods, bottled foods, kneaded foods, dried foods, powdered foods, processed foods, smoked foods, breads, rice, beverages, alcoholic beverages and confectionery. is there.

The present invention provides a pharmaceutical composition or veterinary pharmaceutical composition or health food containing an effective amount of a dried product of Benix nokitake (Taiwan name: Ashishiba) fruit body or its extract or mycelium.
The dose varies depending on the age, body weight, patient sensitivity, symptom level, etc., but the effective dose is usually 0.1 to 10 g, preferably about 1 to 3 g per day for an adult. However, if necessary, an amount outside the above range can be used.

  The hepatic disorder inhibitor containing the dried body of Benix nokitake (Taiwan name: Ashishiba) fruit body of the present invention, its extract or mycelium is formulated for administration by conventional pharmaceutical means.

  That is, tablets, capsules, granules, pills for oral administration are excipients such as sucrose, lactose, glucose, starch, mannit; binders such as hydroxypropylcellulose, syrup, gum arabic, gelatin, sorbit , Tragacanth, methylcellulose, polyvinylpyrrolidone; disintegrating agents such as starch, carboxymethylcellulose or calcium salts thereof, microcrystalline cellulose, polyethylene glycol; lubricants such as talc, magnesium or calcium stearate, silica; lubricants such as sodium laurate It is prepared using glycerol or the like.

  The hepatic disorder inhibitor containing a dried product of the fruit body of Benix nokitake (Taiwan name: Ashishiba), an extract thereof or mycelium of the present invention contains other pharmaceutically or veterinary active compounds. You can also

  The present invention also relates to a liver injury inhibitor that uses a combination of interferon and a liver injury inhibitor that contains a dried product of the above-mentioned Benix nokitake (Taiwan name: Ashishiba) fruit body, an extract thereof, or a mycelium.

As the interferon, a natural type or a gene recombinant type can be used. Specifically, interferon α, interferon α-2a, interferon α-2b, interferon β, and interferon γ can be used, and preferably interferon γ is used. It is done.
A commercially available interferon may be used, or it may be produced and used by a known method.

  The clinical dose of interferon varies depending on age, body weight, patient sensitivity, symptom level, etc., but the effective dose is usually 100,000 to 10 million units per day per adult, preferably 1 million. The unit is 9 million units. However, if necessary, an amount outside the above range can be used.

When dried interferon is used in combination with a liver injury inhibitor containing a dried fruit body of Benix nokitake (Taiwan name: Ashiba), an extract thereof, or a mycelium, the fruit body of Benix nokitake (Taiwan name: Ashiba) is dried. The hepatic disorder inhibitor containing the product, its extract or mycelium is usually administered orally, and interferon is administered intravenously.
The above administration can be carried out almost simultaneously, or can be administered after a time interval.
Moreover, each administration frequency can be administered once or a plurality of times per day within a range in which a necessary amount is administered.

Combined use of the above-mentioned dried fruit of Benix nokitake (Taiwan name: Ashishiba) fruit body, its extract or mycelium and interferon can cause various liver disorders such as alcoholic hepatitis, non-alcoholic steatohepatitis, viral It is useful as an inhibitor for hepatitis, hepatitis A, hepatitis B, hepatitis C, cirrhosis C, etc., especially as an inhibitor for alcoholic hepatitis, non-alcoholic steatohepatitis, hepatitis C, and cirrhosis C It has a more excellent effect, and particularly shows a remarkable effect on hepatitis C.
Therefore, a dried product of Benix nokitake (Taiwan name: Ashishiba) fruit body, an extract thereof, or a hepatic disorder inhibitor using a combination of mycelium and interferon is particularly useful as an inhibitor of hepatitis C.

Hereinafter, although an example is given and the present invention is explained in full detail, the present invention is not limited to these examples at all.
Example 1 Efficacy Test for Alcoholic Liver Injury Sixty 4 week old male rats (Slc: Wister) were bred on a solid diet (laboratory MR stock) for 14 days as a habituation period.
Thereafter, the test was divided into the following 4 groups, and liver extraction and blood collection (20 animals) were performed on the 28th (4 weeks) and the 42nd (6 weeks).
Control group:
Breeding with liquid feed (L10015).
Ethanol administration group:
Breeding with an ethanol-containing liquid feed (L10016), the amount of ethanol per feed was 0% to 2 days, 3%, 2 days to 4 days, 4%, 5 days and later, 5%.
Benix nokitake low dose group:
Similar to the ethanol-administered group, except that 0.3 g / kg of Benix nokitake was administered.
Benix nokitake high-dose group: The same as the ethanol-administered group except that 1.0 g / kg of Benix nokitake was administered.

Blood biochemical tests were performed in each group (42 days (6 weeks) blood sampling), the test results of serum AST (GOT) are shown in FIG. 1, and the test results of serum ALT (GPT) are shown in FIG. The test results of serum total bilirubin are shown in FIG.
1 to 3, it was shown that the increase in GOT, GPT, and total bilirubin by ethanol administration was suppressed by administration of Benix noctum.

The result of measuring the total weight of the extracted liver is shown in FIG.
From FIG. 4, it was shown that the decrease in liver weight by ethanol administration (which is considered to be atrophy of the liver itself due to ethanol intake) is suppressed by administration of Benix nokitake.
In particular, the high dose administration of Benix nokitake was almost the same as the control.

The measurement results of the total cholesterol amount in the liver during the test period of 2 weeks, 4 weeks and 6 weeks are shown in FIG. Incidentally, the total cholesterol amount was shown as mg cholesterol per 1 g tissue wet weight.
From the results of FIG. 5, particularly at 6 weeks, it was shown that the increase in the total cholesterol level due to the administration of ethanol is suppressed by the administration of Benix nokitake.
The above results are thought to be because the administration of Benix nokitake suppressed liver damage caused by ingestion of ethanol.

Enlarged photographs of the excised liver surface are shown in FIGS. 6 to 8 (FIG. 6: control group, FIG. 7: ethanol administration group, FIG. 8: Benix nokitake high dose administration group). In the ethanol administration group (FIG. 7), cell enlargement was confirmed, but in the high dose administration group (FIG. 8), cell enlargement was not confirmed, and the control group (FIG. 6) and It was almost the same.
The above results suggest that the administration of Benix nokitake can suppress the formation of fatty liver by ethanol intake.

Centrilobular hepatocyte vacuolation (lipid droplets) was observed by liver histopathological staining.
Enlarged photographs of the tissues after staining are shown in FIGS. 9 to 11 (FIG. 9: control group, FIG. 10: ethanol administration group, FIG. 11: Benix nokitake high dose administration group).
In the ethanol-administered group (FIG. 10), moderate accumulation of fat (increase in the size of lipid droplets: a particularly prominent portion was indicated by a circle) was confirmed, whereas a high dose of Benix nokitake was administered. In the group (FIG. 11), there was almost no increase in the size of the lipid droplets, and no difference from the control group (FIG. 9) was observed.
The above results also suggest that the administration of Benix nokitake can suppress the formation of fatty liver due to ethanol intake.

Example 2: Effects of Benix nokitake on liver and kidney functions in humans Comparison of blood test results when healthy subjects (volunteers) drink 3L of beer and drink 1 g of Benixnotake mushrooms and when they do not drink Went.
The results are shown in Table 1.
As is clear from Table 1, by taking Benix nokitake, AST (GOT) value, ALT (GPT) value, LDH value, γ-GTP, LAP value, which are indices related to liver damage and hepatitis, Total cholesterol level decreased. In particular, a decrease in the value of hyaluronic acid, which is a marker when necrosis of hepatocytes (cell death due to the influence of others), suggests that stress on hepatocytes is reduced.
From the above results, it was suggested that taking Benikenotake can suppress liver damage (alcoholic liver damage) caused by drinking in humans.

Example 3: Effect of Benix nokitake on patients with nonalcoholic steatohepatitis A patient with nonalcoholic steatohepatitis (female: 33 years old) was administered 3 g of Benixnotake three times a day for 7 months. The graph which shows the time-dependent change of the GOT value, GPT value, and (gamma) -GTP value until after seven months was shown in FIG.
It can be seen from FIG. 12 that the GOT value and the GPT value are clearly improved by taking Benix nokitake.

Example 4: Effect of Benix nokitake on hepatitis C patients Hepatitis C patient (male: 54 years old) with reduced hepatic function marker, taking 3 g of Benix nokitake three times a day, and interferon treatment after one week (interferon) As a result of the combined use of γ), hepatitis C virus was below the detection limit. Thereafter, Benix nokitake was continued for 5 months. FIG. 13 shows a graph showing changes over time in the GOT value, GPT value, and γ-GTP value up to 5 months later.
From FIG. 12, it can be seen that hepatitis C virus is reduced by taking Benix nokitake and interferon together, and as a result, the GOT value and the GPT value are clearly improved.

2 is a graph showing the test results of rat serum AST (GOT) in Example 1. FIG. 2 is a graph showing the test results of rat serum ALT (GPT) in Example 1. FIG. 4 is a graph showing the test results of total bilirubin in rat serum in Example 1. FIG. 2 is a graph showing the results of measuring the total weight of the liver extracted from the rat in Example 1. It is a graph which shows the measurement result of the total cholesterol amount in the liver of a rat in 2 weeks, 4 weeks, and 6 weeks. It is an enlarged photograph of the liver surface extracted from the rat of the control group. It is an enlarged photograph of the liver surface extracted from the rat of the ethanol administration group. It is an enlarged photograph of the surface of the liver extracted from rats of the high dose administration group. Centrilobular hepatocyte vacuolation (lipid droplets) was observed by liver histopathological staining. Enlarged photographs of the tissues after staining are shown in FIGS. 9 to 11 (FIG. 9: control group, FIG. 10: ethanol administration group, FIG. 11: Benix nokitake high dose administration group). It is an enlarged photograph after the tissue dyeing | staining of the liver extracted from the rat of the control group. It is the enlarged photograph after the tissue dyeing | staining of the liver extracted from the rat of the ethanol administration group. It is the enlarged photograph after the tissue dyeing | staining of the liver extracted from the rat of a high dose administration group. It is a graph which shows the time-dependent change of the GOT value, GPT value, and (gamma) -GTP value to 7 months after taking non-alcoholic steatohepatitis patient 3g of Benix nokitake three times a day for 7 months. . GOT up to 5 months after 3 g / day and interferon (γ) combined with interferon (γ) after 3 weeks / day and then continued taking 5 months only for patients with type C cirrhosis It is a graph which shows a time-dependent change of a value, GPT value, and (gamma) -GTP value.

Claims (6)

An inhibitor of liver damage containing a dried product of the fruit body of Benix nokitake (Taiwan name: Kasushiba), its extract or mycelium. The hepatic disorder inhibitor of Claim 1 which uses an interferon together. The liver disorder inhibitor according to claim 1 or 2, wherein the liver disorder is alcoholic liver disorder. The hepatic disorder inhibitor according to claim 1 or 2, wherein the hepatic disorder is non-alcoholic steatohepatitis. The hepatic disorder inhibitor according to claim 1 or 2, wherein the hepatic disorder is hepatitis C. The liver disorder inhibitor according to claim 1 or 2, wherein the liver disorder is type C cirrhosis.