KR20110078525A - Composition for improving hepatic function containing ginseng berry extracts - Google Patents

Abstract

PURPOSE: A composition containing ginseng fruit extract is provided to suppress the increase of intrahepatic cholesterol and to improve liver protection and liver function. CONSTITUTION: A composition for improving liver function contains ginseng fruit extract as an active ingredient. The composition is a solution, suspension, or emulsion. The composition is manufactured in the form of oral formulation, subcutaneous injection, venoclysis, and intramuscular injection.

Description

Composition for improving hepatic function containing ginseng fruit extract {Composition for improving hepatic function containing ginseng berry extracts}

The present invention relates to a composition for improving liver function containing ginseng fruit extract, and more particularly, by containing ginseng fruit extract as an active ingredient, inhibiting ALT (Alanine Aminotransferase) and AST (Aspartate Aminotransferase) activity and increasing liver cholesterol concentration. It relates to a composition for improving liver function.

Modern people are rapidly increasing the possibility of liver damage and liver disease due to dietary changes, excessive stress, drinking, smoking and environmental pollution. There are various diseases such as hepatic impairment, liver cirrhosis, addictive liver disease and alcoholic fatty liver, such as liver damage, liver disease, etc. Among these, especially recently, serious social problems are not only contagious but also contagious. Hepatitis B viral hepatitis B has high morbidity to chronic hepatitis, cirrhosis and liver cancer. Moreover, liver diseases such as hepatitis often cause serious liver damage and complications, which poses a great threat to modern people living in a collective society. Therefore, there is an urgent need for the development of a method for treating hepatitis B disease fundamentally with little recurrence by restoring impaired liver function while effectively treating such acute and active hepatitis disease including hepatitis B.

Currently, the commonly used treatment methods for liver disease are largely divided into diet and pharmaceutical therapy, and in most cases, these two methods are used in combination. Among these methods, a wide variety of drugs are used in the pharmacotherapy for liver disease, but in reality, few drugs have a fundamental therapeutic concept by the etiological approach of liver disease. In the therapy of liver disease, various drugs can be used depending on the type of disease, for example, hepatocellular regeneration accelerators and liver function aids such as urusodesoxycholine acid, silymarin, glutathione, glycyrrhizin, hepahydrate, multivitamins, etc. , Antiviral agents such as acyclovir (ACV: Acyclovir), immunosuppressants such as corticosteroids, 6-mercaptopurine (6MP), azathioprine, and fibrosis inhibitors such as D-phenicillamine, biphenyldimethyldicarboxylate Drugs such as (PMC) and interferon are generally used. However, none of the above-mentioned drugs showed a sufficiently satisfactory effect in the treatment of liver disease.

Accordingly, the present inventors confirmed that the ginseng fruit extract, which is the ground part of ginseng, has a significant effect on liver protection and liver function improvement by inhibiting ALT (Alanine Aminotransferase) and AST (Aspartate Aminotransferase) activity and an increase in liver cholesterol concentration. To complete.

Accordingly, it is an object of the present invention to provide a composition for improving liver function having hepatoprotective and hepatic function effects.

In order to achieve the above object, the present invention provides a composition for improving liver function containing ginseng fruit extract as an active ingredient.

Ginseng fruit extract according to the present invention was excellent in the effect of improving liver protection and liver function by inhibiting the ALT and AST activity and the increase of intrahepatic cholesterol concentration.

The present invention relates to a composition for improving liver function containing ginseng fruit extract as an active ingredient.

The ginseng fruit extract used in the present invention is prepared by extracting the flesh and skin of the ginseng fruit by removing the seed after drying with sunlight or hot air drying with water or ethanol.

The composition according to the present invention may be a pharmaceutical composition comprising a physiologically acceptable pharmaceutical carrier or diluent in addition to the ginseng fruit extract as an active ingredient, and is not particularly limited in the formulation, oral or injectable for oral administration is possible. It can also be used as a food additive.

The compositions of the present invention may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of dry powders which are dissolved in sterile, pyrogen-free water before use, orally formulated, subcutaneous, intravenous or It may be formulated into parenteral formulations such as intramuscular injection.

In the case of oral formulations, the compositions of the present invention may be used in known manner using pharmaceutically acceptable carriers and excipients, for example tablets, troches, sugar-containing tablets, aqueous or oily suspensions, dispersible flours or particles. , In the form of emulsions, soft or hard capsules, syrups or elixirs, which can be prepared in unit dosage form and in multi-dose containers to produce the finished product.

In oral formulations, tablets include inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate and sodium phosphate; Granulating agents such as corn, starch and alginic acid; Disintegrants; Binders such as starch, gelatin and acacia; And lubricants such as magnesium stearate, stearic acid and talc, and the like, and may be prepared in admixture with excipients usable for the manufacture of tablets. Tablets can be used uncoated or coated to inhibit absorption and degradation of the tablets in the gastrointestinal tract. For example, time-inhibiting substances, such as glyceryl monostearate and glyceryl distearate, can also be applied. Hard capsules are a compound of the present invention mixed with an inert solid diluent such as calcium carbonate, calcium phosphate and kaolin, and soft capsules are solvents such as polypropylene glycol, PEGs (polyethylene glycol) and ethanol that can be mixed with water. And the active ingredient in oil solvents such as peanut oil, liquid paraffin and olive oil.

The water-soluble suspending agent is a mixture of excipients and active ingredients suitable for the preparation of water-soluble suspending agents. Excipients include, for example, sodium carboxymethyl cellulose, methyl cellulose, hydroxy-propyl methyl cellulose, sodium alginate, polyvinyl-pi Suspending agents such as rollidone, gum tragacanth and gum acacia; Compounds condensing fatty acids such as polyoxyethylene stearate and alkylene oxides; Compounds in which alkylene oxides are condensed with long fatty acids such as heptadecaethyleneoxycetanol; Compounds which condensate partial esters derived from anhydrous hexitol anhydride and fatty acids, such as polyoxyethylene sorbitol monooleate, with ethylene oxide; Wetting agents; Or dispersing agents. The water-soluble suspending agent may further contain preservatives, colorants, spices and sweeteners.

The oily suspension is a suspension of an active ingredient in a vegetable oil such as olive oil, sesami oil or a mineral oil such as liquid paraffin. For example, a thickening agent such as beeswax, hardened paraffin and cetyl alcohol may be used. It may contain. It may also contain preservatives, colorants, spices, sweeteners, and the like, which can be preserved by adding antioxidants such as vitamin C.

Dispersible powders and particles have an active ingredient in a state of mixing together a dispersing agent, wetting agent, suspending agent and preservative. Suitable dispersing, wetting or suspending agents can be mentioned by way of example already mentioned above. Additional excipients include, for example, sweeteners, spices and colorants.

Water-in-oil emulsions are derived from vegetable oils such as olive oil or mineral oils such as liquid paraffin, and are derived from natural phospholipids such as soy bean lecithin, and esters of anhydrous hecitol or fatty acids such as sorbitan monooleate. And compounds obtained by condensation of ethylene oxide with partial esters derived from anhydrous hexitol anhydride and fatty acids, such as lyoxyethylene sorbitol monooleate, as emulsifiers.

Syrups and elixirs can be prepared by mixing the active ingredients with sweeteners such as glycerol, propylene glycol, sorbitol and sucrose.

Parenteral formulations may be injected as sterile injectable solutions or as suspensions in which the active ingredient is suspended in a non-toxic usable diluent or solvent such as 1,3-butanediol. Among the excipients or solvents that can be used are water, Ringer's solution and isotonic saline solution. Cosolvents such as ethanol, polyethylene glycol, and polypropylene glycol can also be used. In addition, sterile, nonvolatile oils can be customarily used as solvents or suspending solvents. Mixed, non-stimulating, bland fixed oils for this purpose include synthetic mono- and diglycerides. In addition, fatty acids such as oleic acid can be used to prepare the injections. The suppository form is formulated by mixing the drug with a suitable non-irritating excipient, e.g. cocoa butter, polyethylene glycol, which is solid at room temperature but liquid at the rectal temperature and will melt in the rectum to release the drug. May be administered.

Food additives may include beverages, baking, drinks, fats, ice cream, sweets, rice cakes, snacks, baby food, alcoholic beverages, seasonings, retort or canned food.

The cholesterol lowering composition of the present invention may be formulated in an oral dosage form such as a dry powder which is in the form of a solution, a suspension or an emulsion in an oil or an aqueous medium, or dissolved in sterile, water-free water before use. It may also be formulated into parenteral formulations such as subcutaneous, intravenous or intramuscular injection.

In the case of oral dosage forms, for example, tablets, troches, sugar-containing tablets, aqueous or oily suspensions, dispersible powders, etc., in a known manner using a pharmaceutically acceptable carrier or forming agent. Or in the form of oral dosage forms in the form of particles, emulsions, soft or hard capsules, syrups, elixirs, which may be suitably prepared according to unit dosages, forms and the like.

Parenteral formulations may be injected as a sterile injectable solution or as a suspension in which the active ingredient is suspended in a solvent such as a non-toxic usable diluent or 1,3-butanediol. Excipients or solvents that can be used include water, Ringer's solution and isotonic saline solution. Cosolvents such as ethanol, polyethylene glycol and polypropylene glycol can be used. In addition, sterile, nonvolatile oils can be customarily used as solvents or suspending solvents. The suppository form is formulated by mixing the drug with a suitable non-irritating excipient, such as cocoa butter or polyethylene glycol, which is solid at room temperature but liquid at the rectal temperature and will melt in the rectum to release the drug and then enter the rectum. Administration.

When treating a disease using the composition of the present invention, the dose of the active ingredient ginseng fruit extract is the age, weight, general state of health, sex, meal, time of administration, rate of excretion, combination of drugs, disease during treatment Depending on the degree of, etc., depending on the disease can be used every day up to 0.01 to 140 mg / kg, can be used up to 0.5 mg to 7 g per day per patient.

On the other hand, the amount of the compound of the present invention mixed with the carrier material to determine one formulation depends on the mode of administration and the patient being treated. For example, formulations intended for topical application and oral administration of skin to humans will contain from 5 to 95% by weight of carrier materials and from 0.5 mg to 5 g of active ingredient and parenteral administration to humans. Formulations intended for this purpose will contain from 5 to 99% of the carrier composition and from 0.1 mg to 2.5 g of active ingredient.

Hereinafter, the content of the present invention will be described in more detail through examples and test examples. These examples are provided only for understanding the contents of the present invention, and the scope of the present invention is not limited to these examples, and modifications, substitutions, and insertions commonly known in the art may be performed. This is also included in the scope of the present invention.

Example 1 Preparation of Ginseng Fruit Extract

1) Ginseng fruit pretreatment: Raw ginseng fruit was harvested, seed was separated and removed, and then the ginseng fruit dried raw material was prepared by sun drying or hot air drying.

2) Preparation of ginseng fruit extract: 3 g of water was added to 1 kg of dried ginseng fruit extract to extract reflux, and then filtered and concentrated under reduced pressure at 40 to 45 ° C. to obtain 300 g of ginseng fruit extract.

Comparative Example 1 Ginseng Root Extract

3 g of water was added to 1 kg of ginseng root to extract reflux, and then filtered and concentrated under reduced pressure at 40 to 45 ° C. to prepare ginseng root extract.

Test Example 1 Comparison of Ingredients of Ginseng Fruit Extract

<Ginsenoside (Ginseng Saponin) Analysis of Ginseng Fruit and Ginseng Root>

In Example 1 and Comparative Example 1, respectively, ginseng fruit and ginseng root extract were prepared, and then, the extracts were treated with ether to remove fat-soluble components, followed by extracting and concentrating ginsponin with butanol (BuOH). Cenoside component analysis was performed, and the results are shown in Table 1 below.

The ginseng fruit extract prepared in Example 1 had about twice the content of the ginseng root extract prepared in Comparative Example 1 in the content of irradiated phonynin, and ginsenosides were PD (Protopanaxadiol)-"ginsenoside Rb1, Rb2. And Rc and Rd "and PT (Protopanaxatriol)-" Ginsenoside Re, Rg1 and Rg2 "ratios were 0.73 and 3.23, respectively. .

Mineral Analysis of Ginseng Fruit Extract

In order to distinguish that the ginseng fruit extract prepared in Example 1 has the characteristics of 'fruit' different from ginseng, mineral components including vitamins were analyzed, and the results are shown in Table 2 below.

As described above, the ginseng fruit used in the present invention contains more ginseng saponin than the ginseng root, and at the same time, the composition of the saponin is opposite to that of the ginseng root. Could confirm.

Experimental Example 2 Therapeutic Effect on Hepatic Injury Induced by Carbon Tetrachloride

As an experimental animal, 40 male SD (Sprague-Dawley) rats (SLC, Japan) weighing 150 to 200 g were used. The body weight was measured before starting the administration, and divided into three groups (the normal group, the control group administered with carbon tetrachloride only and the treated group of Example 1 administered with carbon tetrachloride and the ginseng fruit extract of Example 1), and eight rats were distributed to each group. Rats were intraperitoneally administered with carbon tetrachloride as a 50% solution mixed with corn oil for 4 weeks twice a week at a dose of 0.75 ml / kg. Example 1 The treatment group suspended 50 g / kg of ginseng fruit extract of Example 1 in a 1% CMC solution and was orally administered once a day and six times a week. In order to investigate the therapeutic effect of the pharmaceutical composition according to the present invention on carbon tetrachloride-induced liver injury, the animals were killed by the animals after 4 weeks of continuous drug administration, and the results were measured. It is shown in Table 3 and Table 4.

ALT and AST activity was measured using a formulated kit (DongYoung Pharmaceutical). The measurement method was according to the instruction manual, and 0.5 ml of ALT and AST substrate solution were added to the test tube, which was warmed at 37 ° C. for 2 to 3 minutes, and then 100 μl of test serum was added, and the AST was reacted at 37 ° C. for 60 minutes. The reaction was carried out for a minute. 0.5 ml of a color developing solution (2,3-ditrophenylhydrazine) was added to terminate the reaction, and the mixture was left at room temperature for 20 minutes, and 5 ml of 0.4N-NaOH was added thereto, and the absorbance was measured at 505 nm.

Inhibitory Effect of ALT Concentration Test substance ALT (U / L) % ALT concentration relative to the control Normal 72 ± 15 - Control group 1930 ± 378 100 Example 1 Treatment Group 943 ± 185 48.8

In the results of Table 3, it was confirmed that the ginseng fruit extract treatment group of Example 1 according to the present invention significantly inhibited ALT activity compared to the control group.

Inhibitory Effect of AST Concentration Test substance AST (U / L) Percentage of AST concentration relative to the control Normal 89 ± 21 - Control group 2120 ± 421 100 Example 1 Treatment Group 1189 ± 158 56.0

In the results of Table 4, it was confirmed that the ginseng fruit extract treatment group of Example 1 according to the present invention significantly inhibited the AST activity compared to the control group.

From the above results, it was confirmed that the ginseng fruit extract of Example 1 according to the present invention has an excellent hepatotoxic effect against hepatotoxicity.

Test Example 3 Therapeutic Effect of Fatty Liver Induced by Ethionine

Three groups of 8 rats were prepared in the same manner as in Example 1, followed by dissolving ethionine (Sigma-aldrich) in physiological saline to 2% (w / v) as a fatty liver inducing substance to rats 200 mg. Administration was subcutaneously twice a week at a dose of / kg. Example 1 The treatment group suspended 50 g / kg of ginseng fruit extract of Example 1 in a 1% CMC solution and was orally administered once a day and six times a week. After the drug administration was continued for 1 week, the animal was lethal to remove the liver, and then perfused with physiological saline solution, and then pulverized with about 4 times of phosphate buffer solution (pH 7.5) to make a homogeneous suspension. The centrifuge was first centrifuged (600 g, 10 minutes) to obtain a supernatant from which nuclei and mima chains were removed, and the second centrifugation (10,000 g, 20 minutes) to remove the mitochondrial fraction, followed by tertiary centrifugation. (10,000 g, 1 hour), and the supernatant was used as an enzyme source. Subsequently, the total cholesterol concentration and the triglyceride concentration in the liver were measured using this enzyme source, and the results are shown in Tables 5 and 6 below.

The total cholesterol content was measured using a kit prepared by the enzyme method (AM 202-K, Asan Pharmaceutical Co., Ltd.), the total cholesterol content was measured according to the instructions of the kit, and the content of triglyceride was prepared by the enzyme method. It measured using the kit (AM 157, Asan Pharmaceutical Co., Ltd.). The triglyceride content was measured according to the kit instructions.

Inhibitory Effect on Increasing Intrahepatic Total Cholesterol Test substance Total Cholesterol (mg / g) % Of total cholesterol concentration relative to the control Normal 13.78 ± 0.45 - Control group 23.15 ± 0.63 100 Example 1 Treatment Group 16.78 ± 0.52 72.5

In the results of Table 5, in the case of the ginseng fruit extract treatment group of Example 1 according to the present invention it was confirmed that the increase in total liver cholesterol concentration is significantly inhibited compared to the control group.

Inhibitory effect of triglyceride concentration increase in liver Test substance Triglycerides (mg / g) % Triglyceride Concentration to Control Normal 6.68 ± 1.04 - Control group 16.41 ± 0.63 100 Example 1 Treatment Group 9.54 ± 0.37 58.1

In the results of Table 6, it was confirmed that the increase in intra triglyceride concentration of the ginseng fruit extract treatment group of Example 1 according to the present invention is significantly inhibited compared to the control group.

Test Example 4 Toxicity Test

<Oral administration>

ICR-based mice and Sprague Dawley (cod hyochang science) were divided into four groups of 10 mice each, orally administered with the extracts of Example 1 of the present invention at doses of 500, 725, 1000 and 5000 mg / kg, respectively. After two weeks of toxicity, none of the four groups died and no symptoms were found.

<Abdominal administration>

ICR mice (25 ± 5 g) and Sprague Dawley (cod hyochang science) were divided into four groups of 10 animals each, and the extracts of Example 1 of the present invention were 25, 250, 500 and 725 mg, respectively. Toxicity was observed for 24 hours after intraperitoneal administration at / kg. There were no deaths in all four groups and no symptoms were apparent in the control group. From the above results, it was confirmed that the extract of the present invention has little acute toxicity.

Hereinafter, an example of the preparation of the pharmaceutical composition will be described, but it is not intended to limit the present invention but merely to explain in detail.

Formulation Example 1 Powder

A powder containing 50 mg of ginseng fruit extract of Example 1, 100 mg of lactose and 10 mg of talc was prepared per package according to the preparation method of powder in the pharmacopeia formulation.

Formulation Example 2 Tablet

A tablet containing 50 mg of ginseng fruit extract of Example 1, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate was prepared per tablet according to the preparation method of the tablet in the pharmacopeia formulation.

Formulation Example 3 Capsule

A capsule containing 50 mg of ginseng fruit extract of Example 1, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate was prepared per capsule according to the preparation method of the capsule in the pharmacopeia formulation.

Formulation Example 4 Injection

Injectable drugs were prepared by appropriately mixing sterile distilled water and a pH adjusting agent for injection into 50 mg of ginseng fruit extract of Example 1 per ampule (2 ml) according to the preparation method of injectable drugs.

Formulation Example 5 Liquid

According to the preparation method of the liquid formulation in the pharmacopeia formulation, 50 mg of ginseng fruit extract of Example 1, 10 g of isomerized sugar, 5 g of mannitol, and purified water were mixed per 100 ml of the formulation.

Formulation Example 6 Healthy Functional Drink

According to the conventional method for preparing a health functional beverage, 1000 mg of ginseng fruit extract of Example 1, 1000 mg of citric acid, 100 g of oligosaccharide, 2 g of plum concentrate, 1 g of taurine, and purified water were added and mixed to make a total of 900 ml, then about 1 After stirring and heating at 85 ° C. for a period of time, the resulting solution was collected by filtration into a sterilized 2 ° C. container, sealed and sterilized and then stored in the refrigerator.

Although the composition ratio is mixed with a relatively suitable component in a preferred embodiment in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, use purpose.

Claims (3)

Composition for improving liver function containing ginseng fruit extract as an active ingredient. The method of claim 1, The composition is a composition for improving liver function for inhibiting ALT (Alanine Aminotransferase) or AST (Aspartate Aminotransferase) activity. The method of claim 1, The composition is a liver function improving composition for inhibiting the increase in total liver cholesterol or triglyceride concentration.