KR100592792B1 - Pharmaceutical Composition for Preventing and Treating Hepatitis Comprising Green Tea Catechins as an Active Ingredient - Google Patents

Abstract

The present invention relates to a liver function improver comprising green tea catechin extracted from green tea as an active ingredient and a pharmaceutically acceptable carrier. The liver function improving agent of the present invention may be widely used for the prevention and treatment of liver diseases such as liver damage, acute hepatitis, chronic persistent hepatitis or liver cirrhosis.

Green tea catechin, liver function improver, hepatitis preventive agent, hepatitis treatment agent

Description

Pharmaceutical Composition for Preventing and Treating Hepatitis Comprising Green Tea Catechins as an Active Ingredient}

Figure 1a is a micrograph showing the liver tissue induced hepatitis by treatment with carbon tetrachloride.

Figure 1b is a micrograph showing the liver tissue prevented hepatitis caused by carbon tetrachloride by the green tea catechin.

Figure 2a is a micrograph showing the liver tissue induced hepatitis by treatment with carbon tetrachloride.

Figure 2b is a micrograph showing the liver tissue treated with green tea catechins, hepatitis caused by carbon tetrachloride.

Figure 3a is a micrograph showing hepatitis-induced liver tissue treated with galactosamine.

Figure 3b is a micrograph showing the liver tissue prevented hepatitis caused by galactosamine by the green tea catechin.

Figure 4a is a micrograph showing hepatitis-induced liver tissue treated with galactosamine.

Figure 4b is a micrograph showing the liver tissue treated with green tea catechins, hepatitis caused by galactosamine.

The present invention relates to a liver function improving agent comprising green tea catechin as an active ingredient. More specifically, the present invention relates to a liver function improver comprising green tea catechin extracted from green tea as an active ingredient and a pharmaceutically acceptable carrier.

Liver is one of the most important metabolic organs in the organs of the body, and performs important functions such as bile secretion, nutrient storage, and detoxification. Metabolic disorders, such as protein metabolism and hepatic brain disease, vitamin metabolism, and poor absorption, may occur, and liver disease may worsen due to infection, fatty liver, cirrhosis, and the like. Hepatic diseases known to date include a variety of hepatic disorders such as acute hepatitis caused by drugs, fatty liver caused by drinking, acute hepatitis caused by viral infections, chronic hepatitis modified by electric acute hepatitis, or cirrhosis accompanied by electrical disorders. Known.

Efforts have been made to develop drugs for treating such hepatic diseases. However, few drugs have been clinically recognized as effective against hepatic diseases. As the most useful method for detecting the pharmacological effects of such drugs, a method of measuring the protective effect against the sudden increase in the level of GOT and GPT in serum caused by carbon tetrachloride (CCl ₄ ) is known. Drugs detected as agents capable of inhibiting hepatic disease have been known to exhibit liver-protective action and detoxifying effect (Kiso, Y., Shoyaku, 36: 238-243). , 1982; Glende, EA, Biochem.Pharmacol., 25: 2163-2169, 1976). In addition, galactosamine, which is known as a substance capable of causing liver disease similar to carbon tetrachloride, may specifically act on the liver and cause various diseases, mainly hepatocellular necrosis and inflammation in liver cells and hepatic portal veins Induced by chronic liver disease, it is known that can cause cirrhosis, cellular tumors.

To date, various products have been developed as a therapeutic agent for hepatic diseases, but practically proved to be effective in silymarin (SIL), biphenyl dimethyl dicarboxylate (DDB), ursodeoxycholic acid ( ursodeoxycholic acid (UDCA) and only a few kinds, these therapeutic agents have the disadvantage that the type of hepatic disease that can be applied is limited. Because of the various functions of the liver, when the therapeutic agent is administered to treat one type of disease, the desired disease can be treated, but unexpected side effects may occur, and when the liver disease is misdiagnosed, the wrong administration of the therapeutic agent Because, hepatic disease may be worse. Moreover, most of the drugs developed to date are for the treatment of hepatic diseases, and the research results on drugs that can prevent liver diseases in advance are insufficient. Therefore, there is an urgent need for the development of drugs that can be used for the prevention and treatment of liver diseases without side effects, and efforts have been made to extract components showing the prevention and treatment effects of liver diseases without side effects from natural product extracts. For example, extracts from green tea may increase the activity of UDP-glucuronosyl transferase, resulting in increased excretion of carcinogens in the liver (see A. Bu-Abbas et al., Food and Chemical Toxicology, 33 (1): 27-30, 1995; OS Sohn et al., Food and Chemical Toxicology, 36: 617-621, 1998). Although it has not been proved, studies on extracts that can improve other liver diseases have not made much progress.

Therefore, there is a constant need to develop drugs that can be used for the prevention and treatment of liver disease without side effects.

Accordingly, the present inventors have made intensive studies to develop drugs that can be used for the prevention and treatment of hepatic diseases, and as a result, the green tea catechin obtained from green tea extract has an excellent effect on the prevention and treatment of hepatic diseases. It was confirmed that this can be used, the present invention was completed.

After all, the main object of the present invention is to provide a liver function improving agent comprising green tea catechin as an active ingredient.

Epigallocatechin-3-gallate (EGCG, C ₂₂ H ₁₈ O ₁₁ , molecular weight 458.4), epigallocatechin (EGC, C ₁₅ H ₁₄ O ₇ , molecular weight 306.3) and epicatechin- Green tea catechins (ECC) containing 3-gallate (ECG, C ₂₂ H ₁₈ O ₁₀ , molecular weight 442.5) as an active ingredient and a pharmaceutically acceptable carrier include: in GTC The content of EGCG, EGC and ECG is not particularly limited, but preferably includes 25 to 70% by weight EGCG, 6 to 30% by weight EGC and 2 to 20% by weight ECG.

In describing the present invention, "Green Tea Catechins (GTC)" is extracted from green tea, epigallocatechin-3-gallate (EGCG, C ₂₂ H ₁₈ O ₁₁ , molecular weight 458.4), Epigallo Other ingredients included in green tea, including catechins (EGC, C ₁₅ H ₁₄ O ₇ , molecular weight 306.3) and epicatechin-3-gallate (ECG, C ₂₂ H ₁₈ O ₁₀ , molecular weight 442.5) in varying amounts, e.g. For example, it means an extract containing less than catechin such as caffeine, ash. The content of the catechin component contained in the GTC is not particularly limited, but is preferably 80% by weight or more based on the weight of the extract, particularly 25 to 70% by weight of the epigallocatechin-3-gallate content in the total extract, More preferably, 6 to 30% by weight of epigallocatechin and 2 to 20% by weight of epicatechin-3-gallate are included.

The manufacturing method of the electric GTC is not particularly limited thereto, but it is not limited thereto. European Patent Publication No. 547370A2, Japanese Patent Laid-Open No. 2-22755, Korean Patent Publication No. 1997-11555, Japanese Patent Publication No. 7-179353 or US Patent No. The known method described in 5,107,000 or the like can be used as it is or as appropriately modified.

Liver function improving agent using the green tea catechin of the present invention can be used for the prevention and treatment of various liver function damages caused by viruses or drugs, as well as the protection of liver cells, prevention and treatment of acute hepatitis, chronic persistent hepatitis It can be used for the prevention and treatment, the prevention and treatment of liver cirrhosis, and especially for the prevention and treatment of fatty liver caused by excessive intake of alcohol. In particular, for acute and chronic hepatitis, it shows the same or superior hepatitis prevention and treatment effect, such as silymarin, biphenyl dimethyl dicarboxylate, ursodeoxycholine acid, which are known as hepatitis agents, and therefore, for the prevention and treatment of liver disease. It can be widely used.

On the other hand, GTC contained as an active ingredient of the liver function improving agent of the present invention is a pharmaceutically acceptable binder (for example, polyvinylpyrrolidone, hydroxypropyl cellulose), disintegrant (for example, carboxymethyl cellulose calcium, starch glycolic acid Sodium), diluents (e.g. corn starch, lactose, soybean oil, crystalline cellulose, mannitol), lubricants (e.g. magnesium stearate, talc), sweeteners (e.g. white sugar, fructose, sorbitol, aspartame), stabilizers (sodium carboxymethylcellulose , Alpha or beta cyclodextrin, vitamin C, citric acid, white lead), preservatives (e.g. methyl paraoxybenzoate, propyl paraoxybenzoic acid, sodium benzoate) and flavors (e.g. ethyl vanillin, masking flavor, menthol flavono, herbal flavor) Can be prepared into pharmaceutical preparations such as tablets, capsules, soft capsules, solutions, ointments or injections.

Acute Toxicity Test of GTC

The non-rodent beagle dogs, 6 to 7 weeks old, were administered orally to the GTC of the present invention and examined for mortality within 24 hours, wherein the females were 6 to 8 kg and the males were 7 to 9 kg. Eight individuals were used each. As a result, the dead individuals do not occur up to 5 g / kg, the GTC of the present invention is safe enough to observe acute toxicity even up to 5 g per kg, it can be safely administered in vivo as a hepatitis preventive and therapeutic agent.

Effective amount

The dosage of GTC, which is an active ingredient in the pharmaceutical composition of the present invention, may be divided into 6 to 30 mg / kg body weight once or three times a day depending on the age, sex, symptoms, administration method or prevention purpose of the patient. . Dosage levels for patients with specific symptoms may vary by those skilled in the art depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of disease, and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. .

Example 1 Obtaining Green Tea Catechin (GTC)

10 g of 70% (v / v) ethanol aqueous solution was extracted with 1000 g of green tea ( Theae sinensis L., Theaceae -var. After completion of the second extraction, it was concentrated in a vacuum rotary evaporator to about 1000 mL. Water was added to the concentrate, diluted 2-3 times, centrifuged at 14,000 rpm for 20 minutes to completely remove solids, and the collected supernatants were extracted twice with 1.2-fold chloroform. Then, the chloroform layer was removed, the aqueous layer was extracted four times with 1.2 times ethyl acetate, and the obtained solution was combined and dried under reduced pressure until the extraction solvent was completely removed. The dried product was dissolved in a small amount of water and lyophilized to obtain GTC powder.

In addition, as a result of measuring the content of the catechin contained in the obtained GTC powder by a known method (see Korean Patent Publication No. 2001-84165), epigallocatechin-3 with respect to the weight of the obtained GTC powder, It was found to contain 37.5% (w / w) gallate, 12.5% (w / w) epigallocatechin, 5.7% (w / w) epicatechin-3-gallate and the remaining amount of other catechins.

Example 2 Preventive Effect of Hepatitis Induced by Carbon Tetrachloride

GTC obtained in Example 1 and known hepatitis therapeutic agents silymarin, DDB and UDCA were used to determine whether hepatitis caused by treatment of carbon tetrachloride.

Saline (Control), GTC 50mg / kg (Experimental Group 1), GTC 100mg / kg (Experimental Group 2), Silymarin 100mg / kg (Experimental Group 3), DDB 100mg / kg (Experimental Group 4) and UDCA 100mg / kg (Experimental Group 5) After oral administration to male rats once a day for 3 days, 0.5 ml / kg of carbon tetrachloride (50% in olive oil), a hepatotoxic substance, was administered to the abdominal cavity of rats to which each experimental group was administered. After 24 hours, the abdominal midline of the rat was incised and collected from the abdominal aorta, and blood was applied to a liver function measurement kit (Sigma Chem. Co., USA) to measure the activity of the serum enzymes AST and ALT ( See table 1).

Comparison of AST and ALT Activities of GTC and Hepatitis Therapeutics of the Invention Treatment group AST (IU / L) ALT (IU / L) Control 262.1 ± 1.2 80.0 ± 9.7 Experimental group 1 153.7 ± 3.6 55.6 ± 5.5 Experiment group 2 122.0 ± 7.8 32.2 ± 6.8 Experiment group 3 167.9 ± 3.2 52.3 ± 6.3 Experimental Group 4 158.5 ± 3.0 39.4 ± 0.4 Experimental group 5 125.6 ± 8.4 28.5 ± 0.7

As shown in Table 1, the experimental group administered with GTC inhibited the enzymatic activity of the AST and ALT of the control group to about 58% and 68%, respectively, it can be seen that hepatitis prevention effect. In addition, although the known hepatitis treatment agent used as a control drug showed a certain level of hepatitis prevention effect, it was found that the effect is lower than the experimental group administered the GTC of the present invention.

Example 3 Therapeutic Effect of Hepatitis Induced by Carbon Tetrachloride

Using the GTC of the present invention and known hepatitis therapeutic agents silymarin, DDB and UDCA, it was examined whether hepatitis caused by the treatment of carbon tetrachloride can be treated.

0.5 ml / kg of carbon tetrachloride (50% in olive oil), a hepatotoxic agent, was administered to the abdominal cavity of male rats, followed by physiological saline (control), GTC 50 mg / kg (experimental group 1), and GTC 100 mg / kg (experimental group 2). ), Silymarin 100mg / kg (Experimental Group 3), DDB 100mg / kg (Experimental Group 4) and UDCA 100mg / kg (Experimental Group 5) were administered orally, respectively. After 24 hours, the abdominal midline of the rat was incised and collected from the abdominal aorta, and blood was applied to a liver function measurement kit (Sigma Chem. Co., USA) to measure the activity of the serum enzymes AST and ALT (see Table 2).

Comparison of AST and ALT Activities of GTC and Hepatitis Therapeutics of the Invention Treatment group AST (IU / L) ALT (IU / L) Control 156.2 ± 0.3 105.4 ± 0.6 Experimental group 1 106.5 ± 2.0 55.4 ± 0.2 Experiment group 2 124.5 ± 3.0 71.3 ± 0.2 Experiment group 3 158.3 ± 3.2 84.9 ± 6.3 Experimental Group 4  88.6 ± 5.5 43.8 ± 0.4 Experimental group 5 101.2 ± 5.2 60.1 ± 0.8

As shown in Table 2, the experimental group administered with GTC inhibited the enzymatic activity of the control group AST and ALT to about 32% and 48%, respectively, it can be seen that hepatitis treatment effect. In addition, while the known hepatitis treatment used as a control drug showed a certain level of hepatitis prevention effect, silymarin (experimental group 3) did not reduce the level of AST at all, and other known hepatitis treatment systems except DDB (experimental group 4). In addition, it can be seen that the treatment effect of the same or lower than the experimental group administered the GTC of the present invention.

Example 4 Preventive Effect of Hepatitis Induced by Galactosamine

Instead of carbon tetrachloride, except for using galactosamine (400 mg / kg in saline), the hepatitis preventive effect of each hepatitis therapeutic agent was compared using the same method as in Example 2 (see Table 3).

Comparison of AST and ALT Activities of GTC and Hepatitis Therapeutics of the Invention Treatment group AST (IU / L) ALT (IU / L) Control 576.0 ± 4.0 276.2 ± 8.0 Experimental group 1 236.3 ± 3.1 115.0 ± 3.9 Experiment group 2 214.0 ± 0.7 108.3 ± 1.7 Experiment group 3 206.3 ± 1.2 110.3 ± 3.8 Experimental Group 4 250.8 ± 0.3 100.5 ± 4.8 Experimental group 5 258.0 ± 1.3  97.5 ± 6.9

As shown in Table 3, the experimental group administered with GTC inhibited the enzymatic activity of the AST and ALT of the control group to about 60% and 59%, respectively, it can be seen that hepatitis prevention effect. In addition, although the known hepatitis therapeutic agent used as a control drug showed a certain level of hepatitis prevention effect, it was found that the effect is the same or lower than the experimental group administered the GTC of the present invention.

Example 5 Therapeutic Effect of Hepatitis Induced by Galactosamine

Instead of carbon tetrachloride, except for using galactosamine (400 mg / kg in saline), the hepatitis prevention effect of each hepatitis therapeutic agent was compared using the same method as Example 3 (see Table 4).

Comparison of AST and ALT Activities of GTC and Hepatitis Therapeutics of the Invention Treatment group AST (IU / L) ALT (IU / L) Control 233.7 ± 4.9 137.4 ± 1.0 Experimental group 1 119.9 ± 3.0 44.5 ± 7.9 Experiment group 2 116.9 ± 4.3 36.2 ± 0.4 Experiment group 3 136.4 ± 2.9 44.3 ± 0.7 Experimental Group 4  89.2 ± 7.1 28.8 ± 0.1 Experimental group 5 117.6 ± 0.9 35.0 ± 0.9

As shown in Table 4, the experimental group administered with GTC inhibited the enzymatic activity of AST and ALT of the control group to about 49% and 68%, respectively, it can be seen that the hepatitis treatment effect. In addition, although the known hepatitis therapeutic agent used as a control drug showed a certain level of hepatitis prevention effect, other known hepatitis therapeutic agents except DDB (experimental group 4), the treatment of the same or lower level than the experimental group administered the GTC of the present invention. It can be seen that the effect.

Example 6 Therapeutic Effect of Hepatitis Induced by Alcohol

Using the GTC of the present invention and silymarin, a known hepatitis treatment agent, it was examined whether hepatitis caused by alcohol can be treated.

To each male rat given oral administration of GTC 100 mg / kg (Experimental Group 1), GTC 200 mg / kg (Experimental Group 2) and silymarin 100 mg / kg (Experimental Group 3) once daily for 8 weeks in an amount of 8 g / kg Oral administration was performed twice a day for 4 weeks. Then, the abdominal midline of the rat was incised and collected from the abdominal aorta, and blood was applied to a liver function measurement kit (Sigma Chem. Co., USA) to measure the activity of the serum enzymes AST and ALT (see Table 5). . At this time, the negative control group was used to administer only saline instead of ethanol, the positive control group was used to administer only ethanol.

Changes in AST and ALT Activity Following Administration of GTC and Silymarin Treatment group AST (IU / L) ALT (IU / L) Negative Control Experimental Group 1 Experimental Group 2 Experimental Group 3 Positive Control Group 67.0 ± 5.0 132.0 ± 1.1 99.0 ± 4.8 96.8 ± 4.0 170.0 ± 7.6 36.0 ± 2.0 70.5 ± 5.1 51.5 ± 7.4 45.0 ± 4.3 97.4 ± 8.4

As shown in Table 5, the positive control group showed hepatitis symptoms due to a sharp increase in AST and ALT levels, but experimental groups 1 and 2 administered with GTC maintained relatively low levels of AST and ALT, which are known. The level was similar to that of silymarin, a hepatitis drug.

Therefore, it is expected that the GTC of the present invention can prevent and treat liver function damage caused by alcohol.

Example 7 : Histopathological Examination

The liver tissues obtained in the control group and Experimental group 2 of Examples 2 to 5 were fixed with an aqueous 10% (v / v) formalin solution, prepared as a tissue section, stained with hematoxylin and eosin, and then, each with an optical microscope. Tissues were observed (see FIGS. 1A, 1B, 2A, 2B, 3A, 3B, 4A and 4B). Figure 1a is a micrograph showing the liver tissue of the control group of Example 2 induced hepatitis by treatment of carbon tetrachloride, Figure 1b is treated with GTC first, then treated with carbon tetrachloride experimental group 2 of Example 2 prevented hepatitis induction Figure 2a is a micrograph showing the liver tissue, Figure 2a is a micrograph showing the liver tissue of the control group of Example 3 in which hepatitis is induced by treatment of carbon tetrachloride, Figure 2b is treated with carbon tetrachloride to GTC induced hepatitis Micrograph showing the liver tissue of Experiment 2 of Example 3 treated and treated with hepatitis, FIG. 3A is a micrograph showing the liver tissue of the control group of Example 4 induced with hepatitis by treatment of galactosamine, FIG. 3B is a micrograph showing the liver tissue of Experiment 2 of Example 4, in which hepatitis was prevented by treating GTC first and then treating galactosamine, and FIG. 4A is galactosamine. Is a micrograph showing the liver tissue of the control group of Example 5 induced hepatitis, Figure 4b is treated with galactosamine GTC treatment of hepatitis-induced liver tissue, the hepatitis of Example 5 It is a micrograph which shows the liver tissue of Experiment group 2. As shown in Figure 1a to Figure 4b, the GTC of the present invention was found to exhibit the prevention and treatment of hepatitis.

Example 8 Determination of Optimum Composition Ratio of GTC

The composition ratio of EGCG, EGC and ECG, which shows the optimal hepatitis prevention and treatment effect, was determined by comparing the hepatitis prevention and treatment effects according to the change in the content of EGCG, EGC and ECG contained in GTC of the present invention.

Example 8-1 Determination of Content of EGCG

12 wt% of EGC and 5 wt% of ECG, and EGCG contents of 10, 20, 30, 40, 50, 60, 70 and 80 wt% of GTC were prepared, respectively, Except for treating each prepared GTC at 100 mg / kg, using the same method as in Example 2, the preventive effect of hepatitis induced by carbon tetrachloride was compared (see Table 6).

Comparison of Hepatitis Prevention Effects of Each GTC EGCG content (% by weight) AST (IU / L) ALT (IU / L) 0 (control) 262.1 ± 1.2 80.0 ± 9.7 10 221.0 ± 3.7 72.2 ± 3.3 20 153.5 ± 3.6 59.2 ± 7.1 30 122.0 ± 7.6 32.2 ± 4.8 40 121.6 ± 5.3 31.8 ± 7.7 50 121.0 ± 6.4 31.6 ± 5.3 60 122.0 ± 5.8 32.8 ± 9.2 70 123.0 ± 3.9 33.0 ± 6.6 80 130.5 ± 6.2 38.6 ± 2.5

As shown in Table 6, when the content of EGCG is 20 to 80% by weight, it was found that the hepatitis preventive effect is excellent, in order to more specifically limit the content of EGCG 20, 22, 24, 26, 28 , 30, 70, 72, 74, 76, 78 and 80% by weight of GTC were prepared, respectively, and the hepatitis preventive effect of each GTC was compared by the same method (see Table 7).

Comparison of Hepatitis Prevention Effects of Each GTC EGCG content (% by weight) AST (IU / L) ALT (IU / L) 0 (control) 262.1 ± 1.2 80.0 ± 9.7 20 153.5 ± 0.2 59.2 ± 7.1 22 151.6 ± 1.6 53.2 ± 8.1 24 148.0 ± 2.4 50.1 ± 3.2 26 122.8 ± 3.8 32.9 ± 7.7 28 122.5 ± 7.1 32.6 ± 5.8 30 122.0 ± 7.6 32.2 ± 4.8 70 123.0 ± 3.9 33.0 ± 6.6 72 129.2 ± 3.3 37.6 ± 2.3 74 128.2 ± 7.4 38.5 ± 6.8 76 129.8 ± 6.3 39.7 ± 7.8 78 130.6 ± 7.9 37.2 ± 1.9 80 130.5 ± 6.2 38.6 ± 2.5

As shown in Table 7, when the content of EGCG is 25 to 70% by weight, it was found that the hepatitis preventive effect is excellent.

Example 8-2 : Content Determination of EGC

GTCs containing 60% by weight EGCG and 5% by weight ECG, each having 5, 10, 15, 20, 25, 30, 35 and 40% by weight of EGC, were prepared, instead of experimental groups 1 to 5. Except for treating each prepared GTC at 100 mg / kg, using the same method as in Example 2, the preventive effect of hepatitis induced by carbon tetrachloride was compared (see Table 8).

Comparison of Hepatitis Prevention Effects of Each GTC EGC content (% by weight) AST (IU / L) ALT (IU / L) 0 (control) 262.1 ± 1.2 80.0 ± 9.7 5 131.1 ± 3.7 42.2 ± 3.3 10 121.9 ± 3.8 33.6 ± 5.5 15 122.0 ± 7.6 32.2 ± 7.8 20 123.6 ± 4.1 32.8 ± 1.4 25 122.0 ± 7.6 32.6 ± 5.3 30 123.6 ± 4.1 32.8 ± 9.2 35 131.2 ± 6.4 38.6 ± 5.3 40 135.3 ± 5.3 39.8 ± 9.2

As shown in Table 8, when the content of EGC is 5 to 30% by weight, it can be seen that the hepatitis preventive effect is excellent, in order to more specifically limit the content of EGC 5, 7, 9, 30, 32 And 34% by weight of GTC were prepared, and the hepatitis preventive effect of each GTC was compared by the same method (see Table 9).

Comparison of Hepatitis Prevention Effects of Each GTC EGC content (% by weight) AST (IU / L) ALT (IU / L) 0 (control) 262.1 ± 1.2 80.0 ± 9.7 5 131.1 ± 3.7 42.2 ± 3.3 7 123.7 ± 5.8 35.7 ± 9.1 9 121.5 ± 4.7 33.0 ± 0.4 30 123.6 ± 4.1 32.8 ± 1.4 32 129.4 ± 5.6 37.9 ± 5.5 34 131.2 ± 6.4 38.6 ± 5.3

As shown in Table 9, when the content of EGC is 6 to 30% by weight, it was found that the hepatitis preventive effect is excellent.

Example 8-3 Determination of Content of EGC

Each of the GTCs containing 60% by weight EGCG and 12% by weight EGC and having ECG content of 5, 10, 15, 20, 25, and 30% by weight, respectively, was prepared instead of experimental groups 1 to 5. Except for treating GTC at 100 mg / kg, using the same method as in Example 2, was compared the preventive effect of hepatitis induced by carbon tetrachloride (see Table 10).

Comparison of Hepatitis Prevention Effects of Each GTC ECG content (% by weight) AST (IU / L) ALT (IU / L) 0 (control) 262.1 ± 1.2 80.0 ± 9.7 5 122.0 ± 7.8 32.2 ± 6.8 10 121.9 ± 3.8 33.6 ± 5.6 15 121.5 ± 7.6 33.2 ± 4.7 20 121.6 ± 4.7 33.8 ± 5.6 25 132.5 ± 6.6 38.2 ± 4.9 30 133.6 ± 4.1 39.8 ± 6.6

As shown in Table 10, when the ECG content is 5 to 20% by weight, it was found that the hepatitis preventive effect is excellent, the ECG content is 1, 3, 5, 20, 22 to more specifically limit this. And 24% by weight of GTC were prepared, and the hepatitis preventive effect of each GTC was compared by the same method (see Table 11).

Comparison of Hepatitis Prevention Effects of Each GTC ECG content (% by weight) AST (IU / L) ALT (IU / L) 0 (control) 262.1 ± 1.2 80.0 ± 9.7 One 131.1 ± 8.7 44.2 ± 3.9 3 123.6 ± 2.5 33.4 ± 5.7 5 122.0 ± 7.8 32.2 ± 6.8 20 121.5 ± 7.6 33.2 ± 4.7 22 128.7 ± 5.5 38.3 ± 6.0 24 130.3 ± 7.4 37.9 ± 4.6

As shown in Table 11, when the ECG content is 2 to 20% by weight, it was found that the hepatitis prevention effect is excellent.

Therefore, according to the results of Examples 8-1 to 8-3, GTC containing 25 to 70% by weight of EGCG, 6 to 30% by weight of EGC and 2 to 20% by weight of ECG is effective in preventing hepatitis. Remarkably excellent. In addition, it was found that GTC containing the above optimal content was remarkably superior in the effect of treating hepatitis caused by carbon tetrachloride and galactosamine.

As described and demonstrated in detail above, the present invention provides a liver function improver comprising green tea catechin extracted from green tea as an active ingredient and a pharmaceutically acceptable carrier. The liver function improving agent of the present invention may be widely used for the prevention and treatment of liver diseases such as liver damage, acute hepatitis, chronic persistent hepatitis or liver cirrhosis.

Claims (7)

delete delete delete delete delete 25 to 70% by weight of epigallocatechin-3-gallate (EGCG, C ₂₂ H ₁₈ O ₁₁ , molecular weight 458.4), 6 to 30% by weight of epigallocatechin (EGC, C) Green tea catechins (GTC) containing ₁₅ H ₁₄ O ₇ , molecular weight 306.3) and 2-20% by weight of epicatechin-3-gallate (ECG, C ₂₂ H ₁₈ O ₁₀ , molecular weight 442.5) A hepatitis therapeutic agent comprising a pharmaceutically acceptable carrier. 25 to 70% by weight of epigallocatechin-3-gallate (EGCG, C ₂₂ H ₁₈ O ₁₁ , molecular weight 458.4), 6 to 30% by weight of epigallocatechin (EGC, C) Green tea catechins (GTC) containing ₁₅ H ₁₄ O ₇ , molecular weight 306.3) and 2-20% by weight of epicatechin-3-gallate (ECG, C ₂₂ H ₁₈ O ₁₀ , molecular weight 442.5) A hepatitis preventive agent comprising a pharmaceutically acceptable carrier.

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