KR20190118270A - Hepatoprotective Composition Comprising Abeliophyllum Distichum Extract - Google Patents

Abstract

The present invention relates to a composition for liver protection, which is derived from a natural plant grown domestically, thereby being able to be used safely while having a liver protection effect, so that it is possible to be used for health food for the prevention and treatment of liver disease and for improving liver function or relieving hangover. More specifically, the present invention relates to a pharmaceutical composition for liver protection and improving liver function containing an Abeliophyllum distichum extract as an active component.

Description

Hepatoprotective Composition Comprising Abeliophyllum Distichum Extract}

The present invention relates to a composition for liver protection that can be used in domestic native plants, without toxicity, can be safely used, and has a liver protective effect, which can be used for the prevention and treatment of liver disease and for improving liver function or hangover.

The liver is one of the important organs in the body that is responsible for the metabolism of the body to properly change the foods ingested in the form of nutrients needed by various tissues and to dispose of the waste products used by the tissues. Specifically, it secretes bile, a digestive fluid, metabolizes proteins, carbohydrates, and fats, stores glycogen and fat-soluble vitamins, synthesizes coagulation factors, removes waste and toxic substances from blood, regulates blood volume, and ages. It functions to destroy one red blood cell.

Various factors can cause liver dysfunction, including mental stress, excessive intake of foods or alcohol containing fat components, viral infections, exposure to harmful substances such as drugs, smoking, and pollutants, and malnutrition. In addition, disorders of liver function can cause the body's defenses and detoxification, causing abnormalities in the immune system, causing other diseases. Disorders of liver function cause a variety of symptoms, including weakness, low blood pressure, frequent contusions and bleeding, tremors, emotional dullness, EEG changes, and fluid accumulation in the abdominal cavity.

In order to discriminate various diseases related to the liver, it is necessary to interpret several biochemical tests comprehensively. For this purpose, several test items are collectively referred to as liver function tests. Major tests include AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), GGT (gamma-glutamyltransferase), bilirubin, as well as total protein, albumin In some cases, items such as lactic acid dehydrogenase (LDH) and ammonia may be added. Among these, AST (GOT) and ALT (GPT) are enzymes present in liver cells, and are mainly released into the blood when hepatocytes are damaged. Therefore, blood AST and ALT levels can be used as markers of liver damage. In the early stages of acute hepatocyte damage, high levels of hepatic AST increase more than ALT, but ALT levels with longer half-lives are more common after 24-48 hours and in chronic hepatocyte damage. In alcoholic hepatitis, AST is further increased.

On the other hand, since the liver is a large buffering capacity, the symptoms do not appear in the early stages of the disease, and it is generally found that the nerves are significantly worsened because there are few nerves that feel pain. Liver cirrhosis and liver cancer are the last stages in common when various liver diseases are chronically progressed. The liver is an important institution for early health care. Therefore, studies have been conducted to provide a composition for liver protection using a natural material that can be safely used, and Patent No. 10-0633851 (Health care or prevention of liver disease containing a heat-dried acid garlic extract as an active ingredient) And a therapeutic composition), registered patent No. 10-1106499 (food composition for liver protection effect, including the bark sprig extract), registered patent No. 10-1702046 (long beetle larvae or fractions thereof as an active ingredient Hepatoprotective and anticancer compositions).

Abeliophyllum distichum is native to Korea and is the only plant in the world. Its name comes from the fact that the fruit is shaped like a round fan, and since it was first discovered in Korea in 1919, it moved to Europe and Japan and is now loved as a great landscaping tree in many countries. In the United States, varieties that have been improved from bark wood are sold. Inhabitants such as Goesan, Yeongdong, Bukhansan, and Jeonbuk Byeonsan Peninsula are limited, and many studies have not been conducted. However, they are effective as anticancer drugs (registered patent No. 10-0706131) or atopic drugs (registered patent no. This is known. Although the bark tree is a rare species, it can be easily reproduced by pruning, giving up, seeding, etc. Therefore, it is necessary to find out the efficacy of the mysterious tree, our precious resource, and to actively breed and utilize it.

Patent Registration No. 10-0633851 Patent Registration No. 10-1106499 Patent Registration No. 10-1702046 Patent Registration No. 10-0706131 Patent Registration No. 10-1729210

It is an object of the present invention to provide a composition that can be used safely without side effects and is effective for protecting liver and improving liver function.

In another aspect, the present invention is to reveal the efficacy of domestic native natural plants, and to provide a new use thereof.

The present invention for achieving the above object relates to a pharmaceutical composition for liver protection and liver function improvement comprising the extract as an active ingredient.

The extract of the present invention may be safely used because it does not show cytotoxicity, and effectively reduces liver function and liver function by effectively reducing AST and ALT, which are indicators of liver function test, in experiments on animal models of alcohol-induced liver injury. It was confirmed that the effect as an improved pharmaceutical composition.

Asteraceae extract may be prepared by a conventional method for preparing plant extracts. That is, the extract may be prepared by extracting and / or fractionating one or more selected from the group consisting of stems, branches, fruits, roots, flowers, leaves, or callus of the thorn tree with water or an organic solvent. The stems, branches, fruits, roots, flowers, leaves or callus may be raw as it is taken, dried or frozen. In addition, it is more preferable to finely chop, extract after grinding or grinding for efficient extraction. Extraction may use any of the methods used for extracting natural products in the art, and for example, cold extraction, heat extraction, ultrasonic extraction, etc. may be used as a method using a juice or a solvent that does not use a separate solvent. It is not limited to this. In the case of extraction using a solvent, the solvent is preferably water or C1 to C4 alcohol or a mixture thereof. In addition, the extract may be further fractionated to further concentrate the active ingredient having an effect on liver protection and liver function improvement. In the following examples, the extract was dissolved in water, and then fractionated sequentially with petroleum ether and ethyl acetate, and finally, the ethyl acetate fraction obtained was used. The extract obtained by extracting with juice or a solvent can be used by itself, concentrated or dried. It is obvious that the drying method may be a conventional method such as spray drying, heat drying, and freeze drying.

The composition of the present invention may be prepared by a method known in the pharmaceutical field for use as a medicament for liver protection and liver function improvement, and may be a carrier or an excipient (pharmaceutically) or a pharmaceutically acceptable carrier. It can be used by mixing with diluent. The composition of the present invention can be formulated as an oral or parenteral preparation to be used as a medicament for liver protection and liver function improvement. The dosage of the active ingredient according to the present invention may be appropriately selected according to the absorbance of the active ingredient in the body, the form of the preparation, the age, sex and condition of the patient, the degree of symptoms, and the like may be administered once a day. It may be administered several times. Typical dosages are 0.001 mg / kgday to 10 g / kgday. Since the composition of the present invention can be used safely without toxicity and side effects, the composition of the present invention can be used safely even when taken for a long time.

The present invention also relates to a health functional food composition for liver protection and liver function improvement comprising the extract of Mt. In particular, the composition of the present invention can be usefully used as a hangover composition. The extract may be added to the health functional food of the present invention preferably 0.01 to 100% by weight. The effective dose of the health food composition of the present invention can be used in accordance with the effective dose of the pharmaceutical composition, but may be less than the above range in the case of long-term intake for the purpose of health and hygiene or health control, The active ingredient may be used in an amount above the above range because there is no problem in terms of safety. The health functional food of the present invention includes the form of tablets, capsules, pills, or liquids, and the foods to which the composition of the present invention can be added include, for example, various foods, beverages, gums, teas, sweets, Alcoholic beverages, chocolate, vitamin complexes, and functional foods.

As described above, the composition of the present invention has no human toxicity and has an excellent effect on liver protection and liver function improvement, and may be usefully used as a pharmaceutical composition and health functional food composition for liver protection and liver function improvement.

1 is a graph evaluating the cytotoxicity of the extract of S. aureus.

Hereinafter, the present invention will be described in more detail with reference to the accompanying examples. However, such an embodiment is only an example for easily describing the content and scope of the technical idea of the present invention, whereby the technical scope of the present invention is not limited or changed. It will be apparent to those skilled in the art that various modifications and variations are possible within the scope of the present invention based on these examples.

EXAMPLE

Example 1: Preparation of the extract

To 500 g of a dry sample of leaves, branches, flowers or immature fruit of the bark, 2L of 70% (v / v) alcohol was added and extracted by stirring for 3 days. The extract was filtered and the filtrate was concentrated to about 500 mL under reduced pressure. 500 mL of petroleum ether was added to the concentrate, followed by stirring. The upper petroleum ether layer was separated and removed. Then, 500 mL of petroleum ether was added to the aqueous layer, followed by stirring twice to separate the aqueous layer. 500 mL of ethyl acetate (Ethyl Acetate) was added to the aqueous layer, followed by stirring. The organic layer was taken three times. The organic layer was recovered, concentrated and dried, and used as an extract.

 Yields of the extracts according to the area of the crypts are shown in Table 1.

Yield of the extract was different depending on the site, but because the difference in efficacy for liver protection in the prior review was not large, the leaf extract was used in the following examples.

Example 2 Preparation of Campus Callus Extract

1 ml of 2,4-D (2,4-Dichlorophenoxyacetic acid) containing MS medium inoculated after cutting the leaves of a certain size to induce callus (callus) at 26 ℃. The induced callus was subcultured at 20 ° C. at 20 ° C. in an MS medium containing 1 ppm 2,4-D and 10 ppm GA (gibberellic acid).

Subcultured callus was harvested and crushed, and then extracted with 10 times of MeOH and stirred for 3 days. The extract was filtered, concentrated and dried.

Example 3: Cytotoxicity Assessment

To measure cytotoxicity, RAW 264.7 cells were placed in 96 well plates at a concentration of 5 × 10 ³ cells / 100 μL. Busy. RAW 264.7 cells were obtained from the Korean Cell Line Bank and were treated with Dulbecco's Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum (FBS), 1% penicillin and streptomycn (P / S) at 37 ° C, 5% CO. Culture was used in ₂ environments. After the treatment with the concentration of 1, 10, 50, 100 ㎍ / ㎖ in the concentration of 1, 10, 50, 100 ㎍ / ㎖ to the dispensed cells prepared in Example 1, the cell survival rate was measured using the MTS assay method.

Figure 1 is a graph showing the results, it shows that the bark extract does not exhibit cytotoxicity can be used safely.

Example 4 Evaluation of Hepatoprotective Efficacy of M. julibrissin Extract

Male Sprague-Dawley rats, weighing 150 g at 5 weeks of age, were purchased from Daehan Biolink (Chungbuk, Negative). Time light / dark cycle) for 1 week. Experimental groups were divided into three groups: normal group (no treatment), control group (alcohol only treatment), and sample administration group (sample + alcohol treatment). Prior to the experiment, fasting was performed for 18 hours in order to prevent the absorption of alcohol through the gastrointestinal tract, which may be caused by feed intake, and water was supplied without restriction.

Alcohol was orally administered 40 mL alcohol 5 mL / kg, each sample was administered orally 500 mg / kg 30 minutes after alcohol administration. After 1 hour of sample administration, blood was collected through the tail vein. After 4 hours, diethyl ether was anesthetized, followed by an abdominal midline, and blood from the abdominal aorta.

Blood AST and ALT levels were measured from the collected blood using an assay kit (Asan Pharmaceutical) using substrate and enzyme reaction. Tables 2 and 3 show the measurement results of blood AST and ALT levels, respectively.

Intoxication with alcohol severely damages the liver tissue membrane, resulting in changes in transport function and membrane permeability, releasing enzymes from cells. As a result, the control group significantly increased blood AST and ALT compared to the normal group. The extracts of the crypts and the extracts of the lumps of callus are significantly reduced in the AST and ALT levels compared to the control group, indicating that the liver is protected against toxic substances. Callus extract was more effective in hepatoprotective effect than that of the extract of S. aureus.

Claims (7)

Liver protection and liver function improving pharmaceutical composition comprising the extract of the aspen.
The method of claim 1,
Pharmaceutical composition for liver protection and liver function, characterized in that for alcoholic liver damage.
The method of claim 1,
The stem extract is a liver composition and liver protection and pharmaceutical composition for improving liver function, characterized in that extracted from one or more selected from the group consisting of stems, branches, fruits, roots, flowers, leaves or callus.
The method according to any one of claims 1 to 3,
The extract is hepatoprotective and liver function improving pharmaceutical composition, characterized in that extracted using water or C1 ~ C4 alcohol or a mixture thereof.
Health functional food composition for liver protection and liver function improvement comprising the extract of M. bran.
The method of claim 5,
Health functional food composition for liver protection and liver function improvement, characterized in that the hangover composition.
The method according to claim 5 or 6,
The stem extract is a liver functional and health functional food composition for improving liver function and liver function, characterized in that extracted from at least one selected from the group consisting of stems, branches, fruits, roots, flowers, leaves or callus.

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