KR100473078B1 - Liver function improver containing Yedeok wood extract as an active ingredient - Google Patents

Abstract

The present invention relates to a liver function improving agent containing the yeast bark X as an active ingredient, and the liver function improving agent of the present invention has a prophylactic and therapeutic effect of liver disease.

Description

Liver function improvement drink using Yedeokpi X as an active ingredient

The present invention relates to a liver function-improving drink containing Yeok bark x as an active ingredient.

In modern times, liver function is impaired due to irregular eating, stress, excessive drinking and smoking, or worse, liver disease develops frequently. Such damage of liver function and liver disease has a fatal effect on the human body and is difficult to recover. There are many kinds of such liver diseases, for example, acute hepatitis and chronic hepatitis, liver cirrhosis, alcoholic fatty liver, hepatitis B virus and the like. In particular, hepatitis B virus is contagious, requiring isolation from society and making it difficult for group life. In addition, chronic hepatitis, cirrhosis, and liver cancer often develop, and these liver diseases are almost incurable and are a real threat to modern people. Therefore, there is a strong demand for the development of a medicament that can effectively treat liver damage and liver disease without side effects or recurrence.

Conventional therapeutic agents for liver disease include liver function aids, antiviral agents such as acyclovir, and hepatocyte regeneration accelerators such as urusodeoxycholic acid, silymarin, glutathione, glycyrizine, hepahydrate, multivitamins, corticosteroids, 6- Immunosuppressants such as mercaptopurine and azathioprine, fibrosis inhibitors such as D-penicillamine, biphenyldimethyldicarboxylate, and interferon have been used, but they do not show sufficient effects in the treatment of liver disease and have side effects and recurrence. There is a high risk that new drugs for liver disease are strongly required.

The wood of the present invention (Malloti Cortex) is a dried dried blood of Mallotus japonicus Mueller Agroviensis, also known as Yaodong or red bean bag. , Yedeok Bark Extract, extracted from Yedeok Bark, is currently in formal use (13 Japanese Pharmacy Room Commentary, 1996, D-4, P1-3, Gwangcheonseolim, Japan; , 1994) and is known to have anti-ulcer and anti-inflammatory activity.

The yeast bark extract can also be obtained by extracting yeast bark usually with an organic solvent such as methanol or water (Homma et al. J. Ag. Chem. Soc., (Jap) 15, 384-396, 1939).

Such Yeokdeokpi X (Japan Drug Pharmacy Standard, P 151-2, Pharmacy Company, 1993) contains 20 kinds of ingredients in addition to Bergenin (12-18% of X) as an active ingredient (Japan 13 amendments to the Pharmacy Room, 1996, D-4, P 1-3, Gwangseom Rim, Japan), Acute toxicity test (mouse, oral) resulted in LD _50> 7170mg / kg toxicity (Hida, etc.) 1), 61-75, 1971), and it is known that there is no effect on the fetus (eg, PK-6, 1979).

The present inventors have completed the present invention by searching for a herbal medicine effective for improving liver function, which has been found to have an effect of preventing or protecting liver disease, which has been used as a conventional dressing agent.

SUMMARY OF THE INVENTION An object of the present invention is to provide a liver function-improving beverage comprising Yeok-Tak X as an active ingredient.

The present invention relates to a liver function-improving beverage comprising as an active ingredient X Molti Cortex.

Yeokdeokpi X of the present invention has a preventive and therapeutic action of liver diseases, the mechanism of action is glutathione sulfur-transferase involved in glutathione-mediated detoxification process and glutathione involved in maintaining the content of glutathione in vivo It seems to be due to the activity inducing action of the reductase.

The liver function improving agent of the present invention may include conventionally used excipients and preservatives such as methyl paraoxybenzoate, propyl paraoxybenzoate, sodium benzoate and the like.

Yeokdeokpi X in the present invention can be obtained through the following conventional extraction method.

10 parts by weight of distilled water was added to 1 part by weight of dried yeokpi dried poultry, and 2 times each for 2 hours, 5 parts by weight were added for 3 hours. It can be dried to obtain Xerox bark. Bergennin is an indicator of yeast bark extract, and if bergennin (C ₁₄ H ₁₆ O ₉ · H ₂ O: 346.29) is quantified in accordance with the drug specifications outside Japan's Pharmacy (151-152, 1993), 12 It contains -18%.

The dosage of the yeast bark extract of the present invention is administered 150 to 500 mg three times a day for an adult, and the dosage may be changed depending on the degree of symptoms or the age and weight of the patient.

The liver function improving agent of the present invention may be prepared in a form suitable for oral administration or parenteral administration according to a conventional preparation method. That is, in the case of oral administration, it may be prepared in the form of tablets, capsules, powders, granules, solutions, syrups, elecils and the like.

In addition, the yeast bark extract of the present invention can be used in the liver function improving beverage, such a beverage can be obtained through a conventional manufacturing method.

The following Preparation Examples and Experimental Examples further illustrate the contents of the present invention, but the present invention is not limited thereto.

Reference Production Example 1

10 kg of distilled water was added to 1 kg of dried Yeokjeok dried poultry, and 2 times each for 2 hours, and 5 liters for the third time. The mixture was extracted by heating in a water bath at 90-100 ℃ for 2 hours, filtered and the filtrate was concentrated under reduced pressure in a water bath and dried. 130 g (13%) was obtained.

Experimental Example 1. Hepatoprotective effect of Yeokdeokpi-X on carbon tetrachloride-induced hepatotoxicity

The SD rats of 150 ± 20g purchased from the Korea Experimental Animal Center were adapted for a week or more under certain conditions (temperature: 20 ± 2 ℃, humidity: 60%, contrast: 12 hours Light / dark cycle). Xerox bark x 150, 300 and 600 mg / kg prepared in Reference Preparation Example 1 as a group were orally administered daily for 7 days, and 0.5 ml / kg of carbon tetrachloride 12 hours and 36 hours after the 7th day of administration. Dissolved in olive oil) was administered intraperitoneally, and after 12 hours of the last administration of carbon tetrachloride, anesthetized with carbonic acid gas (CO ₂ gas) and opened to collect blood and liver tissue. At this time, the experiment was also conducted for the group not administered the cedar bark extract and carbon tetrachloride (normal group), and the group administered the carbon tetrachloride only without the yeast bark extract (control). Combustion of the samples was carried out to prevent toxicity.

For blood and liver tissues taken above, serum s-AST (aspartic acid aminotransferase), s-ALT (serum alanine aminotransferase), SDH (sorbitol dehydrogenase), γ-GT ( The activity of γ-glutamic acid transferase, the contents of LPO (lipid peroxide) and GSH (glutathione) and the activities of GST (glutathione sulfur transferase) and GR (glutathione reductase) in liver tissue were measured (Table 1 In this case, the enzyme source was prepared by preparing a cytosol fraction by a general method, and protein quantification was performed by using Bovine serum albumin (Sigma Fr. IV) as a standard, Lowry, OH. , Rosebrough, NJ and Randall, RJ (1951) J. Biol. Chem., 193, 265). When liver failure is induced, enzymes such as AST, ALT, γ-GT, and SDH, which are selectively present in hepatocytes, are leaked into the blood to increase activity, and the content of lipid peroxides caused by toxic substances increases in the liver. In addition, in the liver, the activities of GR and GST, which are involved in the detoxification of toxic substances, and the content of GSH, which exhibits detoxification effects, are reduced by combining toxic substances. Therefore, drugs that reduce or restore the activity and content of all or part of the blood and liver indices that are increased or decreased due to liver dysfunction have a liver function improvement effect.

TABLE 1

How to measure liver function index

The results of the experiments are shown in Table 2 and Table 3, which are expressed as mean ± standard error, and the statistical significance test was performed using T-test.

TABLE 2

Hepatoprotective Effect of Yeokdeokpi-X on Carbon Tetrachloride-Induced Hepatotoxicity (Indices in Serum)

TABLE 3

Hepatoprotective Effect of Yeokdeokpi-X on Carbon Tetrachloride-Induced Hepatotoxicity (Indicator in Soy Sauce)

#: P <0.01, which is significant when compared with normal group.

$: P <0.05, @: P <0.01 compared with the control group.

The administration of carbon tetrachloride increased s-AST, s-ALT, γ-GT, SDH activity and LPO content in the liver, and markedly decreased the GSH content, GST and GR activity in the liver. The dose of s-AST, s-ALT, γ-GT, and SDH in liver and LPO in liver was decreased in dose-dependently, and the doses of GSH, GST and GR in liver were dose-dependently. Increased.

Experimental Example 2. Hepatoprotective effect of Yeokduk bark x on galactosamine-induced hepatotoxicity

Xerox bark x 150, 300 and 600 mg / kg prepared in Reference Example 1 were orally administered to rats daily for 7 days, followed by 7 days of administration, and then 400 mg / kg of galactosamine 400 mg / kg after 24 hours and 96 hours. Dissolved in the abdominal cavity, respectively, and after the last administration of galactosamine, anesthetized and reopened with carbon dioxide gas 72 hours later, and blood samples and liver tissues were extracted and used for the experiment. The results are shown in Tables 4 and 5 below.

TABLE 4

Hepatoprotective Effect of Yeok-Deok-X on Galactosamine-induced Hepatotoxicity

TABLE 5

Hepatoprotective Effect of Yeokdeok Bark Extract on Galactosamine-induced Hepatotoxicity (Indicator in Soy Sauce)

#: P <0.01, which is significant when compared with normal group.

$: P <0.05, @: P <0.01 compared with the control group.

The administration of galactosamine increased the s-AST, s-ALT, γ-GT, SDH activity in the serum, and the LPO content in the liver, and significantly decreased the GSH content, GST and GR activity in the liver. In the case of pre-administration of Xerox bark extract, serum s-AST, s-ALT, γ-GT, SDH activity and LPO content in liver were dose-dependently reduced. GSH content, GST and GR activity in liver Increased dependently.

Experimental Example 3. The effect of hepatic bark extract on hepatotoxicity induced carbon tetrachloride

0.5 ml / kg of carbon tetrachloride (dissolved in the same amount of olive oil) was intraperitoneally administered to rats after the start of experiment (0 hours) and 12 hours, respectively. 300 and 600 mg / kg was orally administered daily for 7 days, followed by anesthesia after carbon dioxide anesthesia, and then open blood and liver tissue were extracted and used for the experiment. Post-administration of the samples was carried out for the purpose of treating hepatotoxicity. The rest was the same as in Experimental Example 1, and the results are shown in Table 6 and Table 7.

TABLE 6

Hepatotoxic Effects of Yeokdeokpi-X on Carbon Tetrachloride-Induced Hepatotoxicity (Indicators in Serum)

TABLE 7

Hepatotoxic Effects of Yeok-Deok-Phi-X on Carbon Tetrachloride-Induced Hepatotoxicity (Indicators in Soy)

#: P <0.01, which is significant when compared with normal group.

$: P <0.05, @: P <0.01 compared with the control group.

The administration of carbon tetrachloride increased s-AST, s-ALT, γ-GT, SDH activity and LPO content in the liver, and markedly decreased the GSH content, GST and GR activity in the liver. In the post-administration of blood extract, s-AST, s-ALT, γ-GT, SDH activity in serum and LPO content in liver were dose-dependently reduced, and GSH content, GST and GR activity in liver were dose-dependently. Increased.

Experimental Example 4. Effect of Liverwood Extracts on Yeast Extracts on Galactosamine-induced Hepatotoxicity

Intraperitoneally administer 400 mg / kg of galactosamine to rats after starting experiment (0 hours) and 72 hours, respectively, and then added 150, 300 and 600 mg / kg of Yeast bark prepared in Reference Preparation Example 7 7 days after the initial administration. After oral administration for 7 days every day, and after 24 hours, anesthetized blood and liver tissue were extracted and used for the experiment. The rest is shown in Table 8 and Table 9, the same as in Experiment 1.

TABLE 8

Hepatotoxic Effects of Yeok-Deok-X on Galactosamine-Induced Hepatotoxicity (Indicators in Serum)

TABLE 9

Hepatotoxic Effect of Yeokdeok Bark Extract on Galactosamine-induced Hepatotoxicity (Indicator in Soy Sauce)

#: P <0.01, which is significant when compared with normal group.

$: P <0.05, @: P <0.01 compared with the control group.

The administration of galactosamine increased the s-AST, s-ALT, γ-GT, SDH activity in the serum, and the LPO content in the liver, and significantly decreased the GSH content, GST and GR activity in the liver. The dose of s-AST, s-ALT, γ-GT, and SDH in the serum and LPO in the liver was decreased in dose-dependently, and the doses of GSH and GST and GR in the liver Increased dependently.

Experimental Example 5. Hepatic cirrhosis (fibrosis) inhibitory effect

The biliary ligation model according to the method of Kountouras, Biling, BH and Scheuer, PJ (1984) Br.J.Exp Pathol. 65, 305-311) studies the causes, mechanisms, and changes in cirrhosis. It was widely used as an experimental animal model of liver cirrhosis (fibrosis).

SD rats of 15 ± 20g purchased from Korea Experimental Animal Center were acclimated for a week or more under constant conditions (temperature: 20 ± 2 ℃, humidity: 60%, contrast: 12 hours light / dark cycle). The group was opened under anesthesia, ligation of the biliary tract, the muscles and skin were sutured, and then stabilized for 3 days. Yeokdeokpiex 150, 300 and 600mg / kg, silymarin 40mg / kg as a positive control was administered orally for 4 weeks, respectively. At this time, the group was also opened and closed (does not biliary ligation), and did not receive Yeok wood PEX (normal group), but also tested for biliary ligation but not Yeok wood PIX (control). Fasting for 16 hours after the last drug administration, blood was collected from the abdominal aorta under ether anesthesia, and liver tissue was extracted and used for the experiment.

The activity of serum s-AST (aspartic acid aminotransferase) and s-ALT (alanine aminotransferase) in the blood as indicators of hepatic function in the blood and liver tissues taken above was measured by the lateman and Frankel method (Reitman, S. and Frankel, S. (1957) Am. J. Clin. Pathol. 28, 56-63), and the degree of cirrhosis (fibrosis) is an indicator of hydroxyproline content as Jamal et al. , IS, finelli, VN and Que Hee, SS (1981) A simple method to determine nanogram levels of 4-hydroxyproline in biological tissue.Anal. Biochem. 117, 70). When the biliary tract causes liver failure, enzymes such as AST and ALT, which are selectively present in hepatocytes, are leaked into the blood to increase activity, and liver tissue is hardened (fibrosis) to increase the hydroxyproline content. Therefore, drugs that decrease the activity of AST and ALT increased due to hepatic injuries due to biliary tract ligation and decrease the hydroxyproline content in liver tissues have the effect of preventing and preventing cirrhosis (fibrosis).

The results of the experiments are presented in Table 10, which is expressed as mean ± standard error, and the statistical significance test was performed using t-test.

TABLE 10

#: P <0.01, which is significant when compared with normal group.

*: P <0.05, **: P <0.02, ***: P <0.01, which is significant when compared with the control group.

In the control group, the content of hydroxyproline, an indicator of hepatic fibrosis, was 232.4 ㎍ / 0.2 g, which was about 3.8 times higher than that of the 61.1 ㎍ / 0.2 g in the normal group, 6.9 times higher in AST, and 2.9 times higher in ALT. However, Yeokwood P. IX group dose-dependently decreased the hydroxyproline content and AST and ALT activity. Therefore, Yeodeuk P. extract effectively inhibited cirrhosis (fibrosis).

Formulation Preparation Example 1 Tablet

Yedeokpi x 300.0mg

Lactose BP 150.0mg

Starch BP 30.0mg

Pregelatinized Corn Starch BP 15.0mg

Magnesium Stearate 1.0mg

Yeast bark extract was mixed with lactose, starch and pregelatinized corn starch, and then a suitable volume of purified water was added and granulated into powder. The granules were dried and then mixed with magnesium stearate and compressed to obtain tablets.

Formulation Preparation Example 2: Coated Tablet

Yeok Tree Blood X 300.0 mg

Lactose 60.0 mg

Corn starch 300.0 mg

Hydroxypropyl cellulose 3.0 mg

Magnesium stearate 3.0 mg

The mixture of yeast bark extract and lactose and corn starch was granulated through a 1 mm mesh sieve using a hydroxypropyl cellulose solution, dried at 40 ° C. and sieved again. The granules thus obtained were mixed and compressed with magnesium stearate. The resulting central tablet was coated with sugar by an aqueous suspension of sucrose, titanium oxide, talc and gum arabic in a conventional manner. The coated tablets were bred with beeswax.

Formulation Preparation Example 3: Capsule

Yedeokpi x 300.0mg

Starch 1500 100.0mg

Magnesium Stearate BP 2.0mg

Yeast bark extract was mixed with excipients and filled into gelatin capsules to obtain capsules.

Formulation Preparation Example 4 Preparation of Liver Function Improvement Drink

Distilled water was added to 90 ml of Xiadepi x 100.0 mg obtained in Reference Production Example 1, and then 7 to 10 parts by weight of liquid fructose and 0.1 to 0.2 parts by weight of citric acid were added to prepare a beverage for improving liver function.

Formulation Preparation Example 5 Preparation of liver function improving tea

300 mg of dextrin and 300 mg of glucose were added to 300 mg of yeast bark obtained in Reference Example 1, and the mixture was sufficiently mixed to prepare granules, and then dried to prepare tea for improving liver function. It was.

As can be seen in the above experimental example Yekdeokpi X of the present invention has a prophylactic and therapeutic effect of liver disease can be usefully used as a liver function improver or liver function improve drink.

Claims (4)

Liver function improvement drink using Yedeokpi X as an active ingredient. Liver function improvement tea using Yedeok Bark X as an active ingredient. According to claim 1, liver function improving drink, characterized in that the bark wood X containing 12-18% bergennin. According to claim 1, Yeokdeok bark extract is added to 10 parts by weight of distilled water with respect to 1 part by weight of dry Yeok bark crude powder, 2 times each for 2 hours, 5 parts by weight added to the third time and heated extraction in a water bath at 90 ~ 100 ℃ for 2 hours After filtration and filtrate was concentrated under reduced pressure in a water bath, the liver is improved beverage, characterized in that obtained.