JP3130327B2 - Liver dysfunction preventive agent and functional food having hepatic dysfunction preventive action - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an agent for preventing liver dysfunction or a candy comprising as an active ingredient a tea extract extracted from tea leaves using water, alcohol or a mixture thereof as a solvent.

[0002]

2. Description of the Related Art In recent years, among various types of adult diseases, deaths caused by liver diseases are particularly common after cancer, heart disease and cerebrovascular disease. Liver damage is clinically acute hepatitis, chronic hepatitis,
It is classified into fatty liver, cirrhosis, and the like, and the cause is classified into alcoholic, viral, and the like. Usually, acute hepatitis is often caused by a virus, and it is said that excessive drinking of alcohol causes fatty liver and further cirrhosis.

[0003] Hepatic disorders have almost no subjective symptoms, and are often not noticed in mild lesions. Therefore, liver function tests for measuring GOT and GPT in blood are usually performed for early detection of liver damage.

[0004] As described above, hepatic disorders often do not involve subjective symptoms and the like, and their discovery is delayed and it is too late. Even in the case of mild hepatic disorders, it takes a considerable number of days to recover.
It is one of the troublesome diseases along with renal failure. Therefore, a number of studies and studies have been made on prevention and treatment of liver damage from various fields.

[0005]

[Problems to be Solved by the Invention] As measures in daily life to prevent liver damage, avoid overwork.
Intake of balanced food. Avoid alcohol drinking. Avoid taking medicines that may cause liver damage. And the like. However, it is practically difficult to manage these measures while maintaining appropriate measures by keeping a proper diet and a regular life. In addition, it is more difficult to manage without subjective symptoms.

[0006] In addition, there are drugs which are extremely effective for prevention depending on diseases, such as drugs for suppressing hypertension and cholesterol and vaccines for influenza, but none of the preventive agents or preventive foods for hepatic disorder still show sufficient effects. can not see.

On the other hand, tea has long been known as a remedy for health and life extension. The caffeine effect, catechin effect, vitamin C effect, etc. are well known as the medicinal effects. In addition, it is known that catechins obtained by fractionating tea components have particularly pharmacological effects. The effect of the tea is, of course, due to the effect of the fractional components due to these individual effects, but it is considered that the overall effect of all the components contained in the tea or the tea extract appears as the effect of the tea.

Therefore, an object of the present invention is to provide an excellent method using a tea leaf derived from a natural product and having high safety, using an extract simply extracted with water or alcohol without using chemicals dangerous to the human body. An object of the present invention is to provide an agent for preventing or treating liver damage due to viral hepatitis, or a candy for preventing or treating liver damage due to viral hepatitis.

[0009]

The present inventors have SUMMARY OF THE INVENTION, the water from the tea leaves, or the result of extensive studies on pharmacological effects of tea extract extracted with an alcohol or the like, the tea extract viral liver
Found to be effective in preventing and treating liver damage due to inflammation ,
The present invention has been completed.

That is, the present invention comprises a preventive agent for liver dysfunction due to viral hepatitis, comprising a tea extract obtained by extracting tea leaves with water, alcohol or a mixed solution thereof as an extraction solvent, or comprising the tea extract. It is a candy for preventing liver dysfunction caused by viral hepatitis.

[0011] The tea extract of the present invention is an evergreen shrub of Theaceae family, The Sessis L. Leaves are extracted with water or alcohol harmless to the human body or a mixed solution thereof. These may use raw leaves, or may be used by drying the leaves, and further fermented or steamed without fermentation of the leaves, rubbed and dried. May be used. Green tea, sencha,
There are roasted tea, oolong tea and black tea.

The extraction is performed, for example, by adding 500 to 5,000 parts by weight of a solvent to 100 parts by weight of dried tea leaves. As the solvent, water, hot water, hot water, or ethanol or a hydrate thereof is used, and it is preferable that the dried tea leaves are immersed in the solvent or extracted under heating for 3 minutes to 10 hours. The obtained extract is concentrated after removing the extraction solvent. The concentration is such that the extract has a tea extract component of 30 to
Concentrate until about 50 wt%. In addition, 100 parts by weight of dried leaves correspond to about 500 parts by weight of fresh leaves. Also,
In the case of an alcohol extract, before and after concentration, unnecessary components may be adsorbed and removed using activated carbon, acid clay or diatomaceous earth, and the concentrate may be decolorized.

Further, the concentrated liquid may be evaporated to dryness or freeze-dried to obtain a powder. In particular, when the extract is treated with activated carbon and freeze-dried, discoloration during storage of the obtained product can be prevented. In the present invention, the obtained concentrate or powder is used as a tea extract. These may be used as they are, or may be used as drinks, tablets, powders, granules, capsules and the like.
Further, they may be used by dissolving them in purified water, or may be used by adding them to raw materials for food and drink. Addition amount is 1
It is advisable to consume 3 to 10 g in the case of a powder of 1,000 to 3,000 mg in the case of powder per day. As foods and drinks, for example, drinks such as juice, alcoholic beverages, beer, etc., processed cereals such as noodles, bread, rice, biscuits, kneaded products such as sausage, ham, kamaboko, dairy products such as butter, yogurt, chewing gum, candy Confectionery, etc.
Sprinkles, seasonings and the like are used, and they can be added in necessary amounts at an appropriate stage of their production.

The tea extract of the present invention is extracted for 3 minutes to 10 hours as described above, and has a tea extract concentration of 30 to 50 w.
It is concentrated to about t% or dried and solidified or powdered, and is clearly different from ordinary tea beverages in that it is extracted for a long time and concentrated.

The agent for preventing liver damage according to the present invention is administered orally as a concentrated liquid or in the form of a drink, tablet, powder, granule, capsule or the like as described above. The production of these agents involves adding a bulking agent, a binder, a disintegrant, a flavoring agent, a flavoring agent, a coloring agent, etc. to a tea extract concentrate or powder according to the dosage form of the preparation, and a conventionally known conventional agent. It is good to manufacture using the manufacturing method of a formulation. The dosage is about 1,000 to 3,000 days a day for adults in the case of powder.
0 mg, and in the case of a concentrated solution, 3 to 10 g are divided and administered several times a day. This dose corresponds to several times the amount of tea consumed daily. Since this extract is a commonly used ingredient of tea leaves, it has no toxicity, and therefore, there is no problem even if it is administered in excess of the above dose. This way, the virus
It can prevent liver dysfunction due to hereditary hepatitis and is also useful for its treatment.

The functional food according to the present invention is a candy to which the tea extract according to the present invention is added as described above.
A it is useful for the prevention or treatment of liver dysfunction due to viral hepatitis. Thus, simply ingesting the tea extract in the form of medicines or functional foods, or simply dissolving it in fresh water, suppresses the rise in GOT levels in the blood and effectively prevents liver dysfunction due to viral hepatitis. Can be used. That is, the onset of hepatitis can be prevented, and these symptoms can be reduced or treated.

The present invention will be described in more detail and specifically. (1) Production of Tea Extract 50 g of dry tea leaves were leached in 1000 ml of 70 ° C. hot water for 5 minutes and filtered. The pH of the filtrate was about 5.9. The filtrate was immediately lyophilized. In this way, 12 g of a tea extract with warm water in the form of a fine green powder was obtained (containing extract components of 4.2 g of sencha per gram of extract).

In addition, 100 g of dried tea leaves were immersed in 1000 ml of 95% ethanol and extracted at 80 ° C. for 3 hours. After the obtained extract was filtered to remove tea leaves, the extract was concentrated until the tea leaf extract concentration was about 5 wt%. 210 ml of fresh water and 85 g of activated carbon were added to the concentrate, and the mixture was stirred and mixed at about 60 ° C. for 3 hours. Then, after filtering and removing the activated carbon, ethanol and a part of water are removed by evaporation to obtain a tea component concentration of about 50%.
%, 30 g of a dark brown aqueous solution was obtained.

Table 1 shows the component analysis values (wt%) of the hot water extract and the ethanol extract thus obtained.

[0020]

[Table 1] Hot water extraction Ethanol extraction Component name Lyophilized product Purified concentrated liquid Water 1.2 53.6 Lipid 0.6 0.3 Ash 11.5 1.3 Total nitrogen 3.5 1.1 Anhydrous caffeine 7 5.5 2.1 Tannin 31.8 21.4 Epicatechin 3.3 1.4 Epicatechin gallate 2.5 2.1 Epigallocatechin 11.0 5.9 Epigallocatechin gallate 15.0 8.9 Flavonoid ken Ferrol 0.85 0.04 Quercetin 0.74 0.15 Myricetin 0.29 0.10 Total sugar 12.9 10.9 Water-soluble polysaccharide 2.4 0.01 Total ascorbic acid 0.87 ── Theanine 2. 10.5 Total chlorophyll 15.9 ^* ── Calcium 0.06 0.01 Sodium 0.02 0.04 Potassium 5.5 0.62 Magnesium 0.04 0.02 (Unit wt%, * is mg / 100g)

(2) Evaluation Test for Prevention of Liver Injury by Tea Extract (i) Experimental Animals A group of 6 Wistar female rats (10 weeks old, weighing 150 to 160 g; manufactured by Japan SLC Co., Ltd.)
A group I is prepared and administered with physiological saline only, and a group I is administered with galactosamine, one of the liver injury-inducing chemicals.
The tea extract is administered to the groups III to V, and the tea extract is administered to the groups III to V. When the tea extract to be administered is obtained by hot water extraction, a subscript a is added, and in the case of the ethanol extract, Has a subscript b.

(Ii) Preparation of Galactosamine Injection Solution and Determination of Dose The galactosamine administration solution is prepared by using D (+) galactosamine hydrochloride.
Ide) 3.8 g was dissolved in 11 ml of physiological saline and 1
The administration solution (injection solution) was prepared by neutralizing with an aqueous solution of N NaOH.

The dose of galactosamine was 400 mg /
kg, 700 mg / kg, and 1000 mg / kg
Based on the results of preliminary experiments in which the changes in GOT and GPT activities after 24 hours at the level were determined, the dose of galactosamine sufficient to cause liver damage was determined to be 700 mg / kg.

(Iii) Experimental Procedure Details of administration of tea extract and galactosamine and the like to each group and collection of samples for evaluation analysis are as follows.

Details of administration The dose to rats is as shown in Table 2. The tea extract was forcibly orally administered in the amount shown in Table 2 for a total of 5 times 15 hours before, at the time of administration, 8 hours, 24 hours, and 32 hours after the administration of galactosamine. Physiological saline for Group I
The administration was performed once at the same timing as the administration of galactosamine to Groups II to V. The hot water extract (powder) was administered after being dissolved in clear water. In addition, feeding during the experiment was allowed to freely ingest solid feed. The dosage level of the ethanol extract was such that the amount of tannin was the same as that of the hot water extract.

[0026]

[Table 2]

Collection of blood samples and dissection of blood and organs necessary for dissection evaluation were performed for each rat as follows. (1) Blood was collected about 0.6 cc from the tail vein twice at 8 hours and 24 hours after galactosamine administration, and (2) Blood was collected at about 3.0 cc from the abdominal aorta 48 hours later.
cc was collected. (3) Dissection was performed immediately after blood collection 48 hours later, and the liver was stored at −80 ° C. until various measurements were performed. In addition, the blood collection of the group I and the group II to which the tea extract was not administered was performed in the same manner at the same collection time as in the case of the tea extract administration. In addition, all rats had 12
Fasted for hours.

The above series of procedures is as follows.

(Iv) Measurement Items and Measurement Methods Among the parameters related to liver injury, GOT, GPT, and AL indicating liver function were determined from serum separated from collected blood.
The P activity was measured using a measurement test kit (manufactured by Wako Pure Chemical Industries, model number, etc.). In addition, the activity of LCAT, an enzyme that converts free cholesterol in the blood to an ester form, was determined by the method of Kunitomo et al.
apan J .; Pharmacol, 34, 153-1
58, 1984), a typical drug-metabolizing enzyme, liver microsomal P-450, was prepared by the method of Omura et al. (J, Biol. C).
hem. , 239, 2370-2378, 1964).
Tyrosine transaminase (TTA) activity, a marker enzyme for glucocorticoids in blood,
mas et al. (Anal. Biochem., 16,
395-401, 1966).

(V) Statistical processing The obtained measured values are expressed as the mean ± standard error, and the significance of the difference between the measured values with the group II (GA administration group) is Stud.
ent's t-test was applied.

(5) Experimental Results The experimental results are shown in FIGS. FIG. 1- (a), FIG. 1-
(B) shows changes in GOT activity upon administration of a warm water extract and an ethanol extract, respectively. The groups administered with both the warm water extract and the ethanol extract showed a dose-dependent inhibitory effect 24 hours after the administration of galactosamine (GA), and particularly showed a significant inhibition in the group V administered at the highest dose. Also, after 48 hours, the decreasing tendency was maintained.

FIGS. 2- (a) and 2- (b) show changes in GPT activity upon administration of a hot water extract and an ethanol extract, respectively. Almost exactly the same tendency as the GOT result is observed.

FIGS. 3A and 3B show changes in ALP activity upon administration of a warm water extract and an ethanol extract, respectively. In both the warm water and ethanol administration groups, an inhibitory effect was observed 24 and 48 hours after GA administration.

FIG. 4- (a) shows LC in the administration of hot water extract.
4 shows changes in AT activity. Tea extract shows a tendency to suppress LCAT activity.

FIGS. 5- (a) and 6- (a) show the comparison of liver microsomal P-450 and tyrosine transaminase (TTA) activity 48 hours after administration of the hot water extract. Administration of tea extract suppresses P-450,
Shows a tendency to enhance TTA activity.

From these results, it is recognized that the warm water extract and the ethanol extract of tea have a dose-dependent effect of preventing liver damage due to viral hepatitis . In addition to catechins of tannins in the tea extract, it is determined that liver damage is suppressed as an interaction with other components such as flavonoids and vitamin C. In addition, a sufficient effect can be obtained when the dose is in the range of 50 to 200 mg / Kg in the case of the warm water extract and 75 to 300 mg / kg in the case of the ethanol extract.

Next, examples of the present invention will be described.

Example 1 1000 ml of distilled water was heated to 70 ° C., and 50 g of dried tea leaves (commercially available) were wrapped in gauze twice,
It poured and extracted for 5 minutes, stirring. The extract was cooled to 20 ° C. while cooling the outside with ice. The water contained in the tea leaves was collected by squeezing gauze. This extract was filtered with a vacuum filter to obtain about 820 ml of a filtrate. The filtration was then rapidly cooled to -55 ° C and frozen,
Dehydration and drying were performed at atmospheric pressure to obtain about 12 g of a powder (water content: about 1 to 1.5%).

[0038]

Example 2 100 g of tea leaves were added to 95% ethanol 1000
and extracted for 3 hours. After extraction, the tea leaves are removed by filtration, the ethanol is evaporated, and the extract concentration is 5.5 wt.
%. Add 210 ml of fresh water and 8 activated carbons to the concentrate.
5 g was added, and the mixture was stirred and mixed at about 60 ° C. for 3 hours. And
After the activated carbon was removed by filtration, ethanol and some of the water were removed by evaporation, and the mixture was concentrated to a tea component concentration of about 50% to obtain 30 g of a dark brown aqueous solution.

[0039]

Example 3 To 20 parts by weight of the freeze-dried powder obtained in Example 1, 65 parts by weight of lactose, 10 parts by weight of dextrin, 75 parts by weight of talc and an appropriate amount of water were added to form tablets according to a conventional method.

[0040]

Example 4 10 g of the freeze-dried powder obtained in Example 1, 10 g of sucrose, 64 g of starch syrup, 1 g of organic acid, 0.2 g of flavor
And a small amount of water, and the mixture was heated and cooled by a conventional method to produce a candy.

[0041]

Example 5 3 g of the dark brown liquid obtained in Example 2 and sucrose 1
5g, honey 1g, sorbitol 0.3g, amino acid 20
mg, 360 mg of vitamins, 180 mg of organic acid, and 100 mg of fragrance were mixed and heated and cooled by a conventional method to produce a candy.

[0042]

According to the present invention, water or alcohol,
Or because it is a functional food to which a hepatic dysfunction preventive agent due to viral hepatitis or a tea extract is added as an active ingredient, a tea extract extracted as an extraction solvent by using a mixture thereof.
It is obtained by a simple extraction operation, has no side effects, and prevents a decrease in liver function, and is extremely useful as a drug or a functional food.

[Brief description of the drawings]

FIG. 1 (a) shows the change of GOT with time elapsed after administration of GA (galactosamine) when a hot water extract was administered. (B) Changes in GOT with time elapsed after GA administration when ethanol extract was administered.

FIG. 2 (a) shows the change in GPT with time elapsed after GA administration when a hot water extract was administered. (B) Changes in GPT with time elapsed after GA administration when ethanol extract was administered.

FIG. 3 (a) shows the change in ALP activity with time elapsed after GA administration when a hot water extract was administered. (B) Changes in ALP activity with time elapsed after GA administration when an ethanol extract was administered.

FIG. 4 (a) shows the change in the LCAT activity value with the elapsed time after GA administration when a hot water extract was administered.

FIG. 5: (a) GA administration 4 when hot water extract was administered
8 shows liver microsome P-450 after 8 hours.

FIG. 6 (a) GA administration 4 when hot water extract was administered
8 shows tyrosine transaminase (TTA) activity after 8 hours.

[Explanation of symbols]

*, ** and *** indicate the following significant differences from Group II. * P <0.05 ** P <0.01 *** P <0.001

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) A61K 35/78 A23L 1/29-1/308 CA (STN) MEDLINE (STN)

Claims (3)

(57) [Claims] 1. An agent for preventing liver dysfunction due to viral hepatitis, comprising, as an active ingredient, a concentrate or a dry powder of a tea extract obtained by extracting tea leaves with water, alcohol or a mixed solution thereof as an extraction solvent. 2. The prophylactic agent according to claim 1, wherein the extraction is performed for 3 minutes to 10 hours. 3. A method for preventing hepatic dysfunction caused by viral hepatitis, comprising 11 to 16 % by weight of a tea extract concentrate or dry powder obtained by extracting tea leaves with water, alcohol or a mixed solution thereof as an extraction solvent. candy.