JP2002047200A - Antiinflammatory agent for hepatitis c and chronic hepatitis c - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an antiinflammatory agent for hepatitis C and chronic hepatitis C comprising an in vivo antioxidant composition converted into a form simply ingestible every day while taking a daily meal, having high antioxidant actions in vivo and easily digested without causing heartburn. SOLUTION: This antioxidant antiinflammatory agent comprises fermented pulverized materials of edible rice, barleys and wheats and beans and embryos of the edible rice, barleys and wheats and beans or rice bran and is obtained by respectively independently roasting plural kinds of the edible rice, barleys and wheats and beans and embryos of the edible rice, barleys and wheats and beans or rice bran, independently pulverizing the roasted materials, independently steaming the pulverized materials, independently preparing Kojis from the steamed materials, independently adding an alcohol to the prepared Kojis, stopping the fermentation, independently drying the Kojis after stopping the fermentation, removing the alcohol, mixing all the dried powder, producing a first fermented pulverized raw material, independently pulverizing roasted edible seeds and plant bodies containing and vitamin C and vitamin derivatives, mixing all the pulverized materials, producing a second pulverized raw material, mixing the first and second pulverized raw materials and granulating the resultant mixture.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a medicinal composition having a medicinal effect on a person having liver damage such as hepatitis, chronic hepatitis and cirrhosis, in particular, an anti-inflammatory agent for hepatitis C and chronic hepatitis C.

[0002]

BACKGROUND OF THE INVENTION Oxidative stress is associated with aging, arteriosclerosis,
Many disease states, such as cancer, inflammatory conditions, AIDS, radiation injury, ischemia-reperfusion injury, are involved (see Reference 1 and Reference List; the same applies hereinafter). It has been suggested that changes in the oxidative-antioxidant balance are involved in viral hepatitis. <Oxidative stress in chronic hepatitis C> In chronic hepatitis C, lipids and proteins are oxidized, and the amounts of malondialdehyde (MDA) and carbonyl protein in the serum are increased (References 2 to 5). The total thiol amount (t-SH), which reflects the antioxidant ability in plasma, is reduced (References 6 to 6).
8). There have been some reports on the role of iron in chronic hepatitis C, including an increase in hepatic iron storage (Reference 9),
Hyperferritinemia (Reference 10), iron removal treatment by phlebotomy (References 11 to 12), and the like have been reported. Increased transcriptional activity of manganese SOD in monocytes of hepatitis patients was considered to be an adaptive response to oxidative stress (Reference 13). Cytokines such as tumor necrosis factor TNF-α
In e), superoxide is produced by competent cells, and it is known that the amount thereof is excessively produced (Reference 14).

The present inventors have shown that clastogenicity, for example, chromosomal damage is observed in the plasma of patients with chronic hepatitis C (Reference 15). Terms such as "chromosome breakage factor" and "chromosomal aberration inducer (hereinafter also referred to as CF)" are 1970
Since the discovery of such phenomena in humans exposed to radiation in the early ages, it has been used as a biological term to indicate activity in plasma. Clastogenic activity is not a specific factor, but is expressed as a mixture of chromosome-damaging blood oxides. CF includes peroxides of arachidonic acid released from membrane phospholipids and cytokines such as TNF-α, as well as unusual nucleic acids such as inosine triphosphate and diphosphate. The chromosome damage of such components was confirmed using a commercially available standard that can be compared. CF is an endogenous chromosomal abnormality, and their identification is performed by a cytogenetic procedure well-known in studies of exogenous clastogen (chromosomal breakage) administration (Reference 17).

[0004] Since the effects of CF formation and clastogenesis are usually suppressed by superoxide dismutase (SOD), induction of clastogenesis via superoxide has been proposed (Reference 18). Positive CF test is found not only in HIV-infected patients but also in rheumatism, progressive arteriosclerosis, systemic lupus erythematosus (systemic lupus erythematosus), Crohn's disease, ulcerative colitis, familial Mediterranean fever, Behcet's disease, etc. (Reference 19). CF is a biomarker of oxidative stress and disappears upon administration of an antioxidant.

[0005] <CF formation in chronic hepatitis C> According to a recent report (Reference 15), 1 out of 20 patients with chronic hepatitis C
Nine have clastogenic factors found in plasma. Plasma malondialdehyde (MDA) is an indicator of lipid peroxidation
Total thiol (t) reflecting the increase in
Other biological indicators, such as reduced -SH), were also found in most patients. These three indices were significantly different from the 20 normal subjects (risk <0.001). Although aminotransferase (ALT) was elevated in all patients, ALT and markers of oxidative stress (CF, M
(DA, t-SH) was not significant. HCV
-RNA copy numbers were very variable from patient to patient. There was no correlation between viral load, clastogenic activity, MDA, t-SH and ALT in individual results. Histological data (Spearman rank-order test)
As a result, a significant correlation was found between CF and necroinflammation score in liver biopsy (risk rate <0.03). CF
And fibrosis did not show any correlation. In contrast, MDA correlated with fibrosis but not necrosis.

[0006] The fact that CF of another origin was found in the same plasma as well as the anti-chromosomal aberration effect of SOD added to the culture system suggests homology to the CF component of hepatitis patients. Previous reports by the inventors on chronic inflammatory conditions have shown that monocytes are involved in CF formation. A small amount of superoxide is released from monocyte-macrophages
To release TNF-α, one of the clastogenic components. In other words, TNF stimulates those cells and also releases superoxide and CF. This leads to the maintenance of oxidative stress (Reference 20). Liver Kupffer cells make up the majority of macrophages in vivo. They are known to release various mediators such as active oxygen, eicosanoids and cytokines (Reference 21). Kupffer cells are probably the major source of CF in chronic hepatitis C. The superoxide-producing ability of poor cells is about 8 times higher in infectious cells than in non-infectious cells (Reference 22). ATP
With the increase of xanthine and hypoxanthine due to the decomposition of, the increase in xanthine oxidase activity is considered to be a source of superoxide in virus-infected tissues. The inventors also report a marked increase in adenosine deaminase, an enzyme that irreversibly deaminates adenosine to inosine. The formation of inosine triphosphate, another clastogenic component of CF, is the result of elevated adenosine deaminase and is elevated in patients with viral hepatitis.

<Treatment of Chronic Hepatitis C with Interferon-α> IFN treatment is usually performed in the treatment of chronic hepatitis C. Treatment with IFN-α at a dose of 3-5 million units three times a week for 12 months allowed maintenance of HCV-RNA clearance in about 20% of patients. Nine of the 20 patients had normalized serum ALT levels (approximately 40% of literature values were normalized). Our data correlated with normalization of ALT and biological indicators of oxidative stress. Higueras (Reference 5) showed a decrease in MDA and an increase in plasma thiol levels in the plasma of patients after interferon treatment. The effect of IFN on oxidative stress is not antioxidant or free radical scavenging, but anti-inflammatory or antiviral.

<Treatment of chronic hepatitis C with antioxidants>
Given the role of free radicals in the progression of chronic hepatitis C pathology, patients with chronic hepatitis C may be better treated with antioxidants and free radical scavengers. A promising report was treatment with N-acetylcysteine, but was not confirmed in a double-blind clinical trial (Ref. 25). High doses of vitamin E
(1200 IU / day × 8 weeks) suppressed the activation of Ito cells and the expression of collagen genes in 6 patients who were sensitive to interferon. However, this treatment did not suppress serum ALT, viral load, hepatocellular inflammation and fibrosis (Reference 26). Another patient who was sensitive to interferon had 800 IU R for 12 weeks.
ALT levels decreased to 46% in 11 of 23 RR-α-tocophenols (Reference 27). The evaluation of the usefulness of antioxidants is worth further study in interferon alone or in combination.

[0009]

As described above, various anti-inflammatory agents have been conventionally used for liver diseases and the like. Chronic hepatitis, cirrhosis, and liver cancer are diseases that occur subsequently, and the progress of this disease is, of course, not only conventional medicine, but there is no effective method to prevent this, except interferon (IFN). However, this also had little effect other than hepatitis or early chronic hepatitis.

[0010] Even if the liver tissue is improved, if the liver does not grow rapidly, fibrils are formed again and the effect is lost. The liver has a strong proliferative power,
This is a normal condition, and the proliferative power of chronic hepatitis, especially cirrhosis, or liver cancer decreases when the liver cancer develops. The present invention has been made in view of the above circumstances and has been made in order to solve such problems, and an object of the present invention is to provide a high antioxidant effect in a living body in a form that can be easily taken every day while eating a daily meal. An object of the present invention is to provide an anti-inflammatory agent for hepatitis C and chronic hepatitis C comprising a biological antioxidant composition which is easily digested without causing heartburn.

[0011]

Means for Solving the Problems The present inventors have a property that the fermentation extract such as soybean, wheat, rice germ, wheat germ, barley, green tea, yuzu, green leaf, and malt has a liver proliferative power particularly as the molecular weight becomes lower. It was found that. They have also found that it suppresses the transition from chronic hepatitis to cirrhosis, and has an epoch-making effect in cirrhosis, in which the number of fibers decreases, hepatocytes proliferate during that time, and liver function improves.

The inventor of the present invention has found over the years of research that an anti-inflammatory agent comprising a specific fermented extract composition as an essential component has a medicinal effect, and has completed the present invention. The present invention relates to an antioxidant composition comprising edible rice and barley and beans, and fermented and crushed germ or bran of edible rice and barley and beans, comprising a plurality of edible rice and barley and beans and edible rice and barley. Roast the germ or bran of beans independently
Independently crushed roasted food, independently steamed crushed food, independently koji-produced, and independently added alcohol to koji-produced product to stop fermentation and stop fermentation Is dried independently to remove alcohol, all dried powders are mixed to produce a first fermented and ground raw material, and roasted edible seeds and plants containing vitamin C and vitamin C derivatives are independently isolated. It is characterized by pulverizing, mixing all of the pulverized materials to produce a second pulverized raw material, mixing the first and second pulverized raw materials, and granulating the mixture.

The inventor of the present invention has found that the obtained plant composition has a high antioxidant activity in living organisms (an effect of eliminating excess active oxygen and an effect of inhibiting a peroxidation reaction of lipids) and can be easily performed without causing heartburn. Found to be digested. Examples of the edible rice-barley and beans used in the natural antioxidant composition of the present invention include rice, wheat, soybean, corn, barley, red beans and the like. Of these, soybeans and barley are preferably used. Examples of the germ include germs of edible rice and wheat and beans, and wheat germ, rice bran and the like are preferably used. It is preferable that a plurality of these are used.

Suitable combinations of individual edible rice and barley and legumes include soy, barley, wheat germ and rice bran,
Examples of the amount of use include a compounding ratio of 2: 1: 1: 2 by weight. It is preferable that these materials be as fresh and high quality as possible. In particular, germ, especially bran, is easily oxidized, so it is preferable to use one immediately after milled rice.

The roasting in the roasting step of the production of the present invention refers to a method in which the polymerization of active ingredients in raw materials such as edible rice, barley, beans and the like is depolymerized and the heat required to reduce the molecular weight is not burned. It means giving by condition. Each roasting temperature depends on the type of edible rice and wheat and beans and the heating time,
Slowly roast at 80-90 ° C for 5-6 hours. As for the heating method, it is necessary to adopt a means capable of uniformly heating so that the temperature difference between the inner layer and the outer layer of particles such as seeds and embryos is reduced. For this purpose, heating by far infrared rays, uniform heating by a thermostat, heating by a fluidized bed, etc. are employed, but it is preferable to use a pot or container such as stone or pottery.

After roasting each edible rice-barley and legume raw materials, each is ground into a powder in a crushing step. in this case,
Since it is a pulverization to mix well with the seed koji in the koji making process, it is not always necessary to make it into fine powder. After the pulverizing step, the roasted powder is steamed in the steaming step. Steaming may be performed by a usual method, but care should be taken not to overcook. The steaming is for facilitating the next fermentation. However, if the steaming is too much, the fermentation proceeds too much, so that it is sufficient to give the powder a little wetness.

After the steaming step, the seed koji is seeded into the steamed powder for fermentation. Here, fermentation refers to the decomposition of organic matter by microorganisms, and does not refer only to the case where metabolites are converted into simple compounds. For example, mild decomposition by koji mold or yeast is included, and it is rather preferable. During this fermentation process, the enzymatic action of amylase and protease contained in koji mold and the like promotes the reduction of the molecular weight of proteins and the like, facilitating penetration into living organisms, and enhancing the antioxidant action.

In the koji making step, seeds are made for each type of steamed powder. It is preferable that the seed koji is good in powder and about three kinds are prepared, and the seed koji different for each kind of powder is sufficiently mixed. The seeded powder is transferred to a container (made of pottery or plastic) and fermented. The ripening temperature is 35-36 ° C and requires at least 3 days to 2 weeks. Since the number of days varies depending on the temperature and humidity, sufficient attention must be paid to temperature control. Antioxidants are produced during such aging.

After the koji making step, alcohol is independently added to the koji made and stirred to stop fermentation. The fermented products are dried independently to remove alcohol, and the koji raw materials are immediately dried in a drying step. Drying is performed using a usual dryer, but at a drying temperature of 100 ° C. or less. The dried koji raw material is pulverized, and the obtained powders are all mixed. The pulverization method is not limited, and it is preferable to make the powder into a fine powder having a Tyler standard sieve of about 400 mesh. By making it into a fine powder, the absorption of these components in the body of the living body is also improved. Thus, the fermented and ground raw material as the first mixture is obtained. On the other hand, apart from the fermented and crushed raw material obtained by mixing, a mash-like crushed product obtained by roasting and grinding edible seeds and a crushed plant containing vitamin C or a vitamin C derivative are mixed. A stirred second mixture is provided.

Here, edible seeds include sesame, soybean,
Corn, rapeseed and the like can be mentioned, but sesame is most suitable. This is because sesame has vitamin E which suppresses lipid peroxidation
This is because many are contained. These edible seeds must go through the roasting process described above. Plants containing vitamin C or a vitamin C derivative include green tea leaves, young radish leaves, lemon, citron, spinach, etc.
Vitamin C vegetable), but is not limited thereto. Lemon and citron are used as fruit juice.
Among these, green tea leaves are most preferable, and thus, a mixture of young radish leaves and citron juice is used. This prevents oxidation of the edible seeds. It is preferable to dry and pulverize these green tea leaves and young radish leaves. In particular, the green tea leaves are dried while roasting by a normal heating method to form a powder. However, it is preferable to use a fine powder so that the whole amount passes through a Tyler standard sieve 500 mesh.

The mash-like crushed edible seeds and the crushed plant containing vitamin C or vitamin C derivative may be used in the following proportions.
10 parts by weight of vitamin C vegetable and 5 parts by weight of edible seeds per 85 parts by weight of the fermented and ground raw material which is a mixture, or 5 parts by weight of vitamin C vegetables and 5 parts by weight of edible seeds per 90 parts by weight of the fermented and ground raw material Used.

Next, the above-mentioned green tea leaves, sesame, young radish leaves,
The second mixture of citron juice and the separately prepared first mixture, which is the fermented and ground raw material, are mixed and sufficiently stirred. The mixture after the mixing step is finished raw material powder. The finished raw material powder contains about 12% of water, and is subjected to a granulation process in order to improve re-fermentation as it is and to improve the transportability of the product during a chemical reaction. . Granulation is performed while drying in a vacuum using a fluidized granulation dryer. Only in this way is the antioxidant composition completed.

[0023]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiments of the present invention will be specifically described below with reference to the drawings. <Preparation of an anti-inflammatory agent for hepatitis C and chronic hepatitis C comprising an antioxidant composition> 30 parts by weight of fresh soybean, 15 parts by weight of wheat germ, 15 parts by weight of barley and 30 parts by weight of bran immediately after rice polishing,
Each was roasted individually as shown in step 1 of FIG. That is, soybean, wheat germ, barley and bran were each uniformly heated in a thermostat at a temperature of 80 ° C. for 5 hours. The seeds were then ground to a powder as shown in Step 2 of FIG.

The roasted powder was steamed at a temperature of 110 to 120 ° C. for 30 minutes as shown in Step 3 of FIG. Next, the koji mold was thoroughly mixed with the steamed powder and seeded. The seeded powder is transferred to a porcelain container and kept at a temperature of 35 to 36 ° C. for 2 weeks, step 4 in FIG.
Fermented in the koji making process. After koji making, step 5 in FIG.
The alcohol is independently added to the koji-produced product in the step and stirred to stop the fermentation. The fermented product is independently dried at a temperature of 100 ° C. in step 6 in FIG. 1 to remove the alcohol. The dried koji raw material was pulverized into fine powder of about 400 mesh Tyler standard sieve.

In the step 7 of FIG. 1, the obtained powders were all mixed to obtain a fermented and pulverized raw material (first mixture). On the other hand, apart from the fermented and crushed raw materials, step 8 in FIG.
In step 9, sesame was roasted to prepare a mashed mash. In addition, green tea leaves are used in Steps 10 and
In step 11, dry while roasting, and use a Tyler standard sieve 5
A fine powder of about 00 mesh was prepared.

Further, the young leaves of the radish were placed in step 1 of FIG.
In steps 2 and 13, drying was performed while roasting to prepare a fine powder having a Tyler standard sieve of about 500 mesh. Fig. 1
In step 14 of the above, the juice was squeezed to squeeze the juice to prepare citron juice. These sesame mash, green tea leaf powder, young radish leaves and citron juice were all mixed in the step 15 in FIG. 1 to obtain a second mixture.

The first and second mixtures were thoroughly mixed and stirred in step 16 in FIG. 1 to prepare a raw material powder. The mixing ratio used was 85 parts by weight of the first mixture,
Vitamin C vegetable (green tea leaf powder, young radish leaves and citron juice) 1
0 parts by weight and 5 parts by weight of sesame mash were used. The raw material powder was granulated in the step 17 in FIG. 1 to obtain an antioxidant composition.

The antioxidant composition obtained above (hereinafter, referred to as
AOB (abbreviated as AOB) was confirmed by an animal experiment. (Experimental method) All animals were male SD rats (Sprague-
Dawley rat) (weight: 200 g to 220 g) was used.
AOB was used as a 0.5% CMC suspension in in vitro experiments. In addition, lipid peroxidation in rat brain homogenate was used as an index by measuring a TBA-reactive substance (TBARS). In the ex vivo experiment, rats were kept in individual cages, the control group was given only a powdered basic diet, and the AOB group was fed with 1 g or 5 g of AOB in the basic diet and fed as a mixed diet. These rats were bred for one or three days, after which blood samples were collected and used as samples for the ESR method. DMPO (5,5-dimeth
ESR spectrometer (JEOL) using yl-1-pyrroline-1-oxide
-JES-FR80 (manufactured by JEOL Ltd.) was used to examine the superoxide elimination effect in AOB suspensions and blood cells using a superoxide generation system based on hypoxanthine-xanthine oxidase system.

As a result, in the ESR spin trapping method, the AOB group showed a strong superoxide scavenging effect in both in vitro and ex vivo experiments. The 50% inhibition of superoxide in the AOB suspension was 42 μg / ml. The blood level of the control group diluted 12-fold was 0.152 ± 0.017 U / ml in terms of SOD activity, but AOB was lg / day.
AOB group blood breeding after raising for 1 or 3 days at / rat is 0.23
The activity was 3 ± 0.01 U / ml and 0.280 ± 0.042 U / ml. Similarly, AOB group bred at 5g / day / rat has a blood prize of 0.233 ± 0.016
U / ml and 0.280 ± 0.042 U / ml. Furthermore, AO
Group B strongly inhibited lipid peroxidation of rat brain homogenate, and its 50% inhibition rate was 8 μg / ml.

Therefore, AOB containing flavonoids, tannins, tocopherols, ascorbic acid, etc. has a very strong antioxidant action. The strong antioxidant action of AOB is manifested by the additive and synergistic action of the substance obtained by fermentation of the components contained therein, and since the oil content is much less than conventional ones, there is no increase in lipid peroxide due to oxidized oil, so that It is estimated to be.

The inventor has set forth that the AOB active oxygen suppressing composition comprises:
Since it does not contain vegetable oil, it was confirmed that when consumed by an elderly person who secretes less saliva and gastric juice, it is easily digested without dripping the stomach. According to the present invention, a plurality of types of edible rice and barley and beans and germ or bran of edible rice and barley and beans are independently roasted, then ground, then steamed, then koji-produced, and then To a first mixture obtained by mixing all the powders dried after stopping fermentation with alcohol, crushed edible seeds and a crushed plant body containing vitamin C or a vitamin C derivative are added and mixed,
The antioxidant composition obtained by granulating the composition has a high antioxidant effect in a living body and is easily digested without causing heartburn.

<Treatment of chronic hepatitis C with AOB> AO
B is a fermented extract such as soy, wheat, rice germ, wheat germ, barley, green tea, yuzu, green leaves and malt. The components of AOB are shown in Table 1.

[0033]

[Table 1] AOB was analyzed at the Japan Food Research Laboratories, and a list of its components is shown in Tables 2 to 6 as test results.

[0034]

[Table 2]

[0035]

[Table 3]

[0036]

[Table 4]

[0037]

[Table 5]

[0038]

[Table 6]

In addition to rutin, which is present at a high concentration, AOB contains inhibitors of isoflavone daizene and tyrosine kinase and genistein, which is well known for its anticancer activity (Reference 28). Genistein extracted from soybean most effectively prevented the formation of precancerous lesions in rat colon (Reference 29). Genistein and Daizen suppressed the growth of human hepatocellular carcinoma in the culture system (Reference 30). This may be due to the fact that consumption of soy foods in China and Japan causes breast cancer, colon cancer, and prostate cancer to be relatively low (Reference 31).

The superoxide scavenging action of AOB has been measured by an electron magnetic resonance apparatus using a chemical superoxide generating system such as hypoxanthine-xanthine oxidase (Reference 32). The superoxide scavenging action produced by cells has also been shown by stimulated neutrophils (33). AOB inhibits very strong lipid peroxidation and autoxidation of rat brain homogenate (Reference 3)
4). Each component of the AOB component extract was tested with little effect. Lipid peroxidation inhibition rate is AOB
Green tea was 2.8% and wheat germ was 6.6% compared to 64.6% in all cases. Therefore, it is considered that the strong superoxide scavenging action of AOB is a synergistic effect of various flavonoids, oligo components, vitamins and the like which are known to have antioxidant properties.

AOB has few side effects except for slight diarrhea at high doses. It has been shown to be effective in chronic stress and fatigue, convalescent recovery, surgical and radiation treatments, heavy smokers, post-sunlight irradiation, intense exercise, and aging-related injuries. The inventor gave A (laborator: Liquidator) a worker who recovers from the Chernobyl atomic bomb accident.
It was reported that OB administration was effective (Reference 3)
5). As mentioned previously, CF has been found in the plasma of exposed humans. One out of every 20 people checks Liquid Data every year, but they were included in the study in the order in which they were brought in. Since the results of the CF test were not known when the antioxidant was given after blood collection, 3 × 6 g of the antioxidant was given to CF-positive and negative liquidator for 3 months. The clastogenic activity of plasma CF-positive liquidator almost returned to normal (p <0.001).
This lasted for 12 months, even after taking the drug off. Prior to treatment, the plasma values of Liquida without clastogenesis actually remained the same. In only a few cases or short-term observations given, there was no clinical improvement in liquid data. With 20 liquidators visiting the hospital twice a month to get medicines, it can be understood that the general condition is improving. In fact, most Liquida reports that their workforce has improved. No side effects were seen.

After these encouraging results were obtained, the effect of treating chronic hepatitis C patients with AOB on oxidative stress was examined. AOB was given for 3 months x 6g as in Liquida. The AOB group was compared to placebo, which looked the same and had the same appearance. Envelopes were randomly placed and managed by individuals who were not involved in the patient's treatment. All participants in the test obtained written permission. Criteria for grouping were clinical, biochemical, and in particular, whether or not they had positive antibodies to hepatitis C virus. Liver biopsy was performed before treatment. Alcoholism, tobacco poisoning,
He was previously on interferon therapy or taking other antioxidants.

In the case of interferon therapy, three markers of oxidative stress in plasma were measured: CF-test, MDA (Yagi method), and total SH (Eleman method). Blood was collected on the day before the treatment, and on the first day after the treatment was completed and three months after the drug was stopped. At present, the treatment has been completed for 7 AOB and placebo groups, respectively. These one
The following Table 7 (values of oxidative stress biomarkers and alanine aminotransferase before and after treatment with AOB and Placebo) shows the CF, MDA, t-SH amount, and ALT value of the four individuals.

[0044]

[Table 7]

[0045] In the AOB-administered group, CF returned to normal levels, and was normal after the drug withdrawal as described in the Liquida group. On the other hand, the placebo group did not show a decrease in clastogenic activity after 3 months, and showed the initial value 3 months after the withdrawal. In the AOB-administered group patients, MDA was lower in the AOB group than in the placebo group, but was significantly higher even after the CF value was lowered.

In the AOB-administered group patients, plasma thiol slightly increased in both groups, but remained lower than normal (Table 7). Because low SH is a major source of circulating glutathione in the liver, it may reflect liver dysfunction rather than oxidative damage. The average ALT value is A
It was significantly lower after treatment in the OB group, as was the individual result. These tended to rise again after drug withdrawal. In fact, there was no change in the placebo group.

Table 8 shows the results of comparison between the AOB group and the IFN group.

[0048]

[Table 8]

In both groups, the clastogenicity was reduced, but the reduction was more significant with AOB than with IFN. The amount of MDA was reduced in both groups but was higher than normal. SH was similar, rising but still low. The ALT level was higher than that of the IFN group at the time of AOB administration, but recovered to a level higher than that of the IFN group. This value did not return to normal during the course of administration. Liver biopsy and HCV-RN
The results of A are still under study.

Further, two other cases of this clinical test will be described. <First case> Patient F. M. Chronic C at the end of 1995
Diagnosis of hepatitis B, 3x6g in March 1997, for 3 months,
Beginning with AOB treatment, then 2 × 6 g, before treatment, the CF test showed a moderate increase in clastogenic activity (+ 8%). ALT is 121 IU / L. It became normal in July 1997, CF was negative, and ALT was reduced to 49 IU / L. The patient felt pretty good and decided to continue AOB 3g a day. ALT also normalized in October 1998, reaching a normal value of 30 IU / L. October 1998 Patient discontinued AOB. April 1999 normal values (ALT2
7 IU / L, AST18 IU / L).

At the start of treatment, viremia, 95000c
opies / ml. No viral RNA was detected in May 1999. The patient had an AOB in October 1998 six months ago.
Because the drug was withdrawn, this result was classified as "having a sustained effect." Patients are not receiving interferon or other antioxidants. <Second case> Patient P. L. Chronic C at regular screening in 1988
Hepatitis B is diagnosed. Transamylase was significantly reduced by interferon treatment for 10 months in 1995, but HCV-RNA viremia remained. Treatment was not well tolerated for patients, leukopenia was 199
That was the reason for discontinuing treatment at the end of five years. 199
When the patient started AOB treatment (3 x 6 g) for 3 months in April 6 years, liver biopsy data showed chronic hepatitis C with cirrhosis (Metavir score, A
2F4, A = grade, F = fibrosis). Transaminase is 4-5 times the normal value, CF test is highly positive (+16
%). After three months, the transaminase had 154 IU /
L, CF test negative. Patient is AO until late 1996
B was continued at a dose of 2 × 6 g daily, followed by 2 × 3 g until the end of 1997. During this time, the CF test remained negative (6 normal), but the ALT increased to 3 times normal. The patient's general condition improved, and she was able to work that she could not do during interferon treatment. In addition to suspicion of liver cancer by imaging diagnosis, an increase in α-fetoprotein was determined in December 1997 for liver transplantation. The liver function at that time was still satisfactory. The patient took AOB until the day of surgery, and the three zones suspected of liver cancer were examined histologically. No malignant cells were found and the diagnosis was "regenerated"
Met.

The transplanted livers were well tolerated and patients received immunosuppressive drugs such as cortisone and prograf. A
OB was discontinued from the day of surgery. The patient's general symptoms were satisfactory. However, 199 months after transplantation
In May 2008, hepatitis recurred, and transaminase increased 6-fold from normal. The CF test was strongly positive (+ 18%). Liver biopsy showed moderate hepatitis (A2F0). Depending on the needs of the patient
AOB was added to the treatment schedule at a dose of 3 × 6 g, even 2 × 6 g, daily for 3 months. The CF test became negative after 2 months and the ALT decreased slowly, but about 10
The high value of 0 IU / L followed. According to a liver biopsy one year after transplantation, the Metavier score was 0 for malignancy, and A0F1 was slightly positive for fibrosis. Patients travel abroad frequently and have very active and professional work as photographers. AOB prevented malignant transformation in this case, but failed to affect liver fibrosis and cirrhosis. In the acute phase of hepatitis recurrence, AOB acted on inflammation and necrosis (from A2F0 to A0F1).

The anti-inflammatory agent consisting of AOB has a useful effect on chronic hepatitis C patients. In the acute and chronic phases,
AOB affects necrotic-inflammatory lesions by superoxide scavenging and antioxidant effects. Early administration of AOB may prevent progression to fibrosis and cirrhosis. The anti-tumorigenic effect of AOB is of great interest in the treatment of liver cancer. AOB is patient J. M. Whether or not there is an antiviral effect as indicated by more patients must undergo long-term treatment and observation.

As already mentioned, the strong superoxide scavenging activity of AOB is the result of a synergistic effect of various components. Flavonoids represent the most active, as only a small amount of antioxidant vitamins and oligo components are present. Various flavonoids are present in AOB. Each of the identified flavonoids should be protected by a patent as their activity has not been studied separately.

[0055] Compared to interferon, AOB is at least as effective as IFN in patients' general symptoms.
Considering the serious side effects, it is more effective. NA
Other antioxidants such as C and Vitamin E are ineffective,
No good results were obtained as with AOB. (List of references) 1) Sies, H. (ed): Oxidative stress. New York, Academ
ic Press 1985.

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4) Romero MJ, Bosch-Morell F, Romero B,
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6) Beloqui 0, Prieto J, Suarez M, Gil
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[Brief description of the drawings]

FIG. 1 is a diagram showing a flowchart of a method for producing an anti-inflammatory agent for hepatitis C and chronic hepatitis C according to the present invention.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Huang Chuang, Taipei, Beitou District, No. 474, 2F, Yanyang Co., Ltd. F-term (reference) 4C076 AA31 BB01 CC04 CC16 CC35 GG12 4C088 AB12 AB15 AB45 AB61 AB62 AB73 AB74 AB77 AC04 AC05 MA07 MA41 MA52 ZA75 ZB11 ZB33

Claims (4)

[Claims] 1. A plant antioxidant composition comprising soybean, barley, wheat germ and rice bran, and tea, wherein roasted soybean, barley, wheat germ and rice bran are independently roasted, followed by grinding, steaming, and koji making. , Fermented and crushed raw materials obtained by mixing all of the powders obtained through drying, crushed oilseed crushed material, roasted and crushed tea leaf powder, independently dried and crushed green leaves A mixed anti-inflammatory agent for hepatitis C and chronic hepatitis C, which is obtained by adding and mixing a mixed and crushed product consisting of powder of the above and fruit juice independently squeezed and granulating the mixture. 2. The oil seeds are sesame seeds, the green leaves are at least one of radish leaves and spinach, and the fruit juice is at least one of lemon and citron juice. The anti-inflammatory agent for hepatitis C and chronic hepatitis C as described above. 3. The anti-inflammatory agent for hepatitis C and chronic hepatitis C according to claim 1, wherein the weight ratio of the soybean, barley, wheat germ and rice bran is 2: 1: 1: 2. . 4. The tea leaves and green leaves powder and the fruit juice 5 to 1 to 85 to 90 parts by weight of the fermented and ground raw material.
The anti-inflammatory agent for hepatitis C and chronic hepatitis C according to claim 1, wherein 0 parts by weight and 5 parts by weight of the oil seed are added and mixed.