KR102493496B1 - Composition for alleviating and improving liver damage derived from natural products - Google Patents

Abstract

The present invention relates to a natural product-derived composition for relieving and alleviating liver damage. According to the present invention as described above, a drug-induced liver damage treatment agent according to the present invention uses a substance obtained from a natural product and does not cause side effects, and thus can protect and restore the damaged liver, so that it is possible to effectively control drug-induced liver damage.

Description

Composition for alleviating and improving liver damage derived from natural products

The present invention relates to a natural product-derived composition for mitigating and improving liver damage.

The liver is an organ located on the right side of the upper abdomen that makes and stores various nutrients and performs important functions such as excreting waste and toxins from the body. The liver is an organ that plays a central role in nutrient metabolism. A normal human liver weighs about 1,500 g, and abnormal liver function causes problems in nutrient metabolism in the body, turning glucose into glycogen or converting protein into albumin. There is an abnormality in liver function, such as converting to or dissolving unnecessary substances and passing them into bile. In the case of mild liver damage, liver cells can be restored again if you take a mental break, but in a busy modern society, you can't afford to take a break, so liver disease is aggravated.

In general, hepatitis, which causes inflammation of the liver, accounts for most of the liver diseases, and can be divided into acute hepatitis and chronic hepatitis according to the aspect, and viral hepatitis, alcoholic hepatitis, and drug-induced hepatitis according to the cause. Liver diseases caused by these abnormalities include fatty liver, hepatitis, cirrhosis, and liver cancer. Although liver disease is treated with exercise, abstinence from alcohol, diet, and drug therapy, it is fundamentally difficult to completely cure liver disease, so the development of effective and improved liver disease treatment or protective agents is continuously needed.

In particular, since liver cells are destroyed and liver function is reduced to less than half, no special symptoms appear, so there are many cases where the treatment period is missed, so more attention is needed.

If the degree of damage to the liver is severe, the color of urine changes to brown, and symptoms of jaundice appear, in which the eyes and skin turn yellow. If the liver is swollen or enlarged by inflammation, it may be palpable when the area under the right rib is pressed.

The present inventor obtained information about a composition for treating and improving liver damage that had been slandered in China, confirmed that the composition actually had an effect of restoring and improving liver damage, and completed the present invention based thereon.

Korean Patent Registration No. 10-1549630

An object of the present invention is to provide a composition showing the effect of restoring and improving damaged liver using a natural product-derived extract.

Another aspect of the present invention is to provide a method for preparing a composition for recovery and improvement of the liver.

Another object of the present invention is to provide a pharmaceutical composition for treating liver disease comprising the composition.

Another object of the present invention is to provide a food composition for preventing and improving liver disease comprising the composition.

Technical tasks to be achieved in the embodiments are not limited to those mentioned above, and other technical tasks not mentioned will be considered by those skilled in the art from various embodiments to be described below. can

In order to achieve the above object, the present invention is a group consisting of Injin, Cheongho, Geumjeoncho, Sanchija, Rhubarb, Hwanggeum, Tosaja, Raw malt, Eoseongcho, Jeoryeong, Uiin, Bokryeong, Cheonryunja, Mokhyang, Hubak, Yeongyo and Gyenaegeum It provides a composition for treating and improving liver damage, comprising an extract of one or more selected natural substances from

Specifically, the composition is a first mixed extract obtained from a mixture consisting of injin, chungho, geumjeoncho and sanchija in a weight ratio of 2: 2: 1: 1; A second mixed extract obtained from a mixture composed of rhubarb, gold, tosaja, raw malt, eoseongcho, jeoryeong, uiyiin, and bokryeong in a weight ratio of 3:1:1:2:1:1:2:1; And a third mixed extract obtained from a mixture consisting of cheonryunja, mokhyang, humpak, yeonkyo, and gyenaegeum; characterized in that it comprises a mixture in a weight ratio of 4:2:1.

In the present invention, the "Injin" is also called wormwood, and is mainly composed of spherical capitulum flowers with a diameter of 2 mm, and is composed of filamentous leaves, inflorescence shafts, and thin stem segments, , vagina light greenish-brown-dark brown. It is known to have the effect of treating liver fever, cooling heat, urinating well, removing dampness, and defeating jaundice.

In the present invention, the "blue tiger" is also called azalea wormwood, and is a stem with a peduncle with almost no leaves and is 60-90 cm long. The outer surface of the stem is yellowish brown, the quality is hard, and the bent surface is fibrous. The leaves are greenish-brown, with many fine wrinkles, rolled up, and brittle, and the flower stalk is yellowish green. This drug has a peculiar smell and a neutral taste. It is known to have the effect of brightening the eyes, eliminating parasites, relieving blood and heat at the same time, relieving heat, and treating ailments.

In the present invention, the "Geumjeoncho (金錢草)" is also called a long bottle flower, and is a name given because the shape of the leaf resembles money. It is known to play a role in turning off heat, removing dampness, relieving swelling, and urinating well.

In the present invention, the "mountain gardenia" refers to a well-ripe fruit of Gardenia jasminoides Ellis, an evergreen shrub belonging to the Rubiaceae family. It was used for the treatment of congested eyes or insomnia by urinating well, cooling heat, and releasing toxicity.

In the present invention, it is known that the "rhubarb" has the effect of purifying and detoxifying blood, making stools come out well, and removing blood to relieve menstrual pain.

In the present invention, it is known that it has the effect of detoxifying while releasing the "golden" heat, preventing miscarriage of pregnant women, stabilizing fetal period, hemostasis, cooling heat and drying moisture.

In the present invention, the "tosaja ()" belongs to the Convolvulaceae family, and the seeds of Saesilsam, which are spherical-disc-shaped and have a diameter of 1-3mm and weigh about 100mg per 100, are used as medicine. It is known to be effective in preventing miscarriage in pregnant women, brightening the eyes, protecting the liver and kidneys, and treating diarrhea.

In the present invention, the "raw malt" strengthens the spleen, opens the stomach, eliminates enemies, helps digestion, relieves stagnation, clears the phlegm, prevents milk from coming out, and helps childbirth is known to do

In the present invention, the "Eoseongcho (魚腥草)" is called Eoseongcho because it has a fishy smell, and is 20-35 cm long and 2-3mm in diameter, vertically wrinkled, and has clear nodes. It is known to have a detoxifying effect, drain pus, and soothe swollen wounds.

In the present invention, the "jeoryeong (猪)" is a sclerotium of a mushroom belonging to the mushroom family, and is mainly used to excrete moisture into urine and prevent hepatitis.

In the present invention, the "uiyiin (薏苡仁)" is known to have the effect of lowering the qi, supplementing the energy of the lungs and spleen, stopping diarrhea, cooling the heat, and soothing the swelling of the wound.

In the present invention, the "Bokryeong (茯)" is a parasitic cell of a pine tree, and the skin is called Bokryeongpi, and the fungus grows while wrapping the pine root inside the pine tree root (茯神), the white color inside is Baekbokryeong, and the red one It is called Jeokbokryeong, and all are used as medicine. The yakseong is ordinary, and the taste is sweet and calm. It has diuretic and stomachic effects, so it is effective for edema, nephritis, cystitis, etc., and is known to be used for bronchial disorders or gastroenteritis.

In the present invention, the "Chunnyeonja" has the effect of passing through the liver, having analgesic action, urinating well, eliminating parasites, dissipating heat and contracting the gallbladder to discharge bile It is known that there are

In the present invention, the "wood scent" is a perennial herbaceous plant belonging to the Asteraceae family, and is known to be used to normalize the movement of the stomach and intestines, and to be used as a treatment for acute gastroenteritis or to stimulate appetite.

In the present invention, the "Hubbaek" is the bark of an evergreen tree belonging to the Lauraceae family, which treats dysentery, lowers the body, lowers blocked walls, relieves asthma, and brightens eyes and ears. It is known to be effective.

In the present invention, the "Yeonkyo (連翹)" is known to be effective in detoxifying, and the extract is effective in treating inflammation, removing parasites, and having the effect of breaking through clumps or crowding.

In the present invention, the "gyenaegeum (鷄內金)" is known to have the effect of strengthening the stomach, helping digestion, and removing heat.

In another aspect of the present invention, (a) after mixing and pulverizing ingin, chungho, geumjeoncho and sanchija in a weight ratio of 2: 2: 1: 1, hot water extraction at 80 to 90 ° C. for 2 to 3 hours, followed by first mixing obtaining an extract; (b) Rhubarb, Hwanggeum, Tosaja, Raw malt, Eoseongcho, Jeoryeong, Uiyiin, and Bokryeong were mixed in a weight ratio of 3:1:1:2:1:1:2:1, and then pulverized to a concentration of 50 to 50% with 80% ethanol. Obtaining a second mixed extract by reflux extraction at 65 ° C. for 3 to 4 hours; (c) obtaining a third mixed extract by hot water extraction at 100 ° C. for 2 hours after mixing Cheonnyeonja, Mokhyang, Hubak, Yeongyo and Gyenaegeum; And (d) mixing the first mixed extract to the third mixed extract at a weight ratio of 4:2:1 and concentrating in the dark; It provides a method for producing a composition for recovery and improvement of the liver, including.

Another aspect of the present invention is to provide a pharmaceutical composition for treating liver disease comprising the composition.

In the present invention, the liver disease may be acute hepatitis, chronic hepatitis, fatty liver disease, liver cirrhosis, liver fibrosis, liver cancer, drug-induced hepatitis, jaundice, liver cirrhosis, etc., without being limited thereto, and liver damage and any abnormal health caused thereby. It can be used to include all states.

The composition of the present invention may further include suitable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions. In addition, it can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods. Suitable formulations known in the art are preferably those disclosed in the literature (Remington's Pharmaceutical Science, recently, Mack Publishing Company, Easton PA). Carriers, excipients and diluents that may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate, mineral oil, and the like. When the composition is formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, It is prepared by mixing gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.

As used herein, the term "administration" means providing a given composition of the present invention to a subject by any suitable method.

The pharmaceutical composition of the present invention is the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human thought by a researcher, veterinarian, physician or other clinician, that is, alleviation of the symptoms of the disease or disorder being treated It can be administered in a therapeutically effective amount, which is an amount that induces It is apparent to those skilled in the art that the therapeutically effective dosage and frequency of administration of the pharmaceutical composition of the present invention will vary depending on the desired effect. Therefore, the optimal dose to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of the active ingredient and other ingredients contained in the composition, the type of formulation, and the patient's age, weight, and general health Condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, can be adjusted according to various factors including drugs used simultaneously. For desirable effects, the pharmaceutical composition of the present invention may be administered in an amount of 1 to 10,000 mg/kg/day, preferably 1 to 200 mg/kg/day, and may be administered once a day or several times. It can also be administered in divided doses.

The pharmaceutical composition of the present invention can be administered to a subject by various routes. All modes of administration are contemplated, eg oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine intrathecal or intracerebrovascular injection.

In addition, the composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, or biological response modifiers for liver protection, liver disease, or prevention or treatment of complications.

Another aspect of the present invention is to provide a food composition for preventing and improving liver disease comprising the composition.

There is no particular limitation on the type of food. For example, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, etc., including all health foods in the usual sense. can do.

When the food composition of the present invention is prepared as a beverage, it may contain additional ingredients such as various flavoring agents or natural carbohydrates, like conventional beverages. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin and cyclodextrin or synthetic sweeteners such as saccharin and aspartame may be used. The natural carbohydrate is included in 0.01 to 10% by weight, preferably 0.01 to 0.1% by weight, based on the total weight of the food composition of the present invention.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol , carbonation agents used in carbonated beverages, and the like. In addition, the composition of the present invention may include fruit flesh for preparing natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of the above additives is not particularly limited, but is preferably included within the range of 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.

According to the present invention as described above, the drug-induced liver damage treatment agent according to the present invention uses substances obtained from natural products, so it does not cause side effects and can protect and restore liver damage caused by liver damage. damage can be dealt with effectively.

BRIEF DESCRIPTION OF THE DRAWINGS Included as part of the detailed description to aid understanding of the embodiments, the accompanying drawings provide various embodiments and, together with the detailed description, describe technical features of the various embodiments.
1 shows the results of a cytotoxicity test on hepatocytes to determine whether the composition of the present invention exhibits cytotoxicity.
Figure 2 shows the results of confirming whether the composition of the present invention shows hepatocellular protective effect in vitro .
Figure 3 shows the results of animal experiments to see whether the composition of the present invention actually shows an effect in vivo .

The following embodiments combine elements and features of the embodiments in a predetermined form. Each component or feature may be considered optional unless explicitly stated otherwise. Each component or feature may be implemented in a form not combined with other components or features. In addition, various embodiments may be configured by combining some components and/or features. The order of operations described in various embodiments may be changed. Some components or features of one embodiment may be included in another embodiment, or may be replaced with corresponding components or features of another embodiment.

Throughout the specification, when a part is said to "comprising" or "including" a certain element, it means that it may further include other elements, not excluding other elements, unless otherwise stated. do. In addition, terms such as “… unit”, “… unit”, and “module” described in the specification mean a unit that processes at least one function or operation, which is hardware or software or a combination of hardware and software. can be implemented as Also, “a or an”, “one”, “the” and like terms are used herein in the context of describing various embodiments (particularly in the context of the claims below). Unless otherwise indicated or clearly contradicted by context, both the singular and the plural can be used.

Example 1. Preparation of composition for alleviating and improving liver damage

The composition for alleviating and improving liver damage of the present invention was prepared through the following steps.

(a) obtaining a first mixed extract by mixing and pulverizing Injin, Cheongho, Geumjeoncho and Sanchija in a weight ratio of 2:2:1:1, followed by hot water extraction at 83° C. for 2.5 hours; (b) Rhubarb, Hwanggeum, Tosaja, Raw malt, Eoseongcho, Jeoryeong, Uiyiin, and Bokryeong were mixed in a weight ratio of 3:1:1:2:1:1:2:1, ground, and then heated to 60°C with 80% ethanol. Extracting under reflux for 3 hours to obtain a second mixed extract; (c) obtaining a third mixed extract by hot water extraction at 100 ° C. for 2 hours after mixing Cheonnyeonja, Mokhyang, Hubak, Yeongyo and Gyenaegeum; and (d) mixing the first mixed extract to the third mixed extract at a weight ratio of 4:2:1 and concentrating in the dark to prepare a composition for alleviating and improving liver damage according to Example 1 of the present invention.

Comparative Example 1. Composition prepared by varying the ratio

It was prepared in the same way as in Example 1, but the four herbs constituting the first mixed extract were all mixed and extracted at the same weight ratio (1: 1: 1: 1), and the first to third mixed extracts were used. It was prepared at a mixing ratio of 5:2:1. This is to confirm whether a better effect appears naturally when the ratio of medicinal materials known to be good for the liver is increased.

Comparative Example 2. Preparation of compositions with different extraction methods

It was prepared in the same way as in Example 1, except that all of the first to third mixed extracts were extracted with hot water for 4 hours at 85 to 90 degrees, which is a temperature for decoction of common decoctions.

Comparative Example 3. Preparation of a composition omitting some medicines

Except for medicinal herbs known to be not directly related to the liver, uiyiin, bokryeong, mokhyang, and gyenaegeum, the ratio of the remaining components of each mixed extract is increased by the corresponding ratio so that the ratio of the first to third mixed extracts remains the same, and the remaining was prepared in the same manner as in Example 1.

Experimental Example 1. Cytotoxicity

In order to first confirm whether the composition of the present invention exhibits cytotoxicity, in vitro experiments were conducted on hepatocytes.

The cell line used in this experiment was HepG2 (human hepatocellular carcinoma cell), a liver cancer cell, and 10% FBS (feral bovine serum) and 1% 100 units/ml of penicillin-strepromycin were added to MEM medium. Using the medium containing this, it was prepared by culturing as a monolayer in a 37°C 5% CO ₂ incubator.

As a result, as shown in FIG. 1, when the composition of Example 1 of the present invention was treated with 1, 5, 10, 25, and 50 ug/ml, respectively, a survival rate of 95% or more was shown even at a high concentration of 50 ug/ml, It was confirmed that there was no toxicity.

Experimental example 2. In vitro Confirmation of hepatocellular protective effect in

In order to confirm whether the composition of the present invention actually has a protective effect on hepatocytes, HepG2 cells prepared in the same manner as in Experimental Example 1 were treated with the compositions of Examples and Comparative Examples of the present invention at concentrations of 1, 10, and 25ug/ml, , After 12 hours, 3% of ethanol and the compositions of Comparative Examples and Examples were treated at the same concentration. After 24 hours, cell viability was calculated using MTT-assay to confirm whether there was actually a protective effect on hepatocytes.

As a result, as shown in Figure 2, it was confirmed that the composition of Example 1 of the present invention exhibits an excellent hepatocellular protective effect in a concentration-dependent manner. On the other hand, all of Comparative Examples 1 to 3 were less effective than Example 1, and in particular, in the case of Comparative Examples 2 and 3, regardless of the concentration, only a similar degree of effect was shown, but rather the survival rate decreased ( Comparative Example 2).

Experimental example 3. In vivo Confirmation of liver damage mitigation effect in

In order to confirm whether the composition of the present invention exhibits liver damage alleviation or treatment effects in vivo , experiments using mice were conducted.

Specifically, male Sprague-Dawley rats weighing around 300 g were used in the experiment. Experimental animals started this experiment after acclimating to the laboratory environment for 2 weeks. During the experiment period, the laboratory environment was maintained at 12-hour light/dark intervals, temperature of 25±2°C and humidity of 55%.

Liver damage was induced by intraperitoneally injecting 100 mg/kg of Thioacetamide (TAA) solution, and when the composition of Example 1 of the present invention was administered in an amount of 20 or 50 mg/kg, GOT (Glutamate-oxaloacetate transaminase, which is an indicator of liver damage) ) and GPT (Glutamate-pyruvate transaminase) changes were analyzed. In the negative control group, physiological saline was administered instead of the composition of Example 1.

TAA was injected three times for a total of one week, and the composition of Example 1 and physiological saline were orally administered once daily. Other than that, they were bred freely.

After one week, the experimental animals were suffocated, blood was collected from the abdominal aorta, and serum (GOT and GPT) was analyzed.

As a result, as shown in FIG. 3, in the case of the negative control group administered with TAA, both indicators were significantly increased, confirming that liver damage had occurred. On the other hand, the experimental group administered with the composition of Example 1 confirmed a significant effect in all experimental groups regardless of the administered dose.

Various embodiments described above may be embodied in other specific forms without departing from their technical ideas and essential characteristics. Accordingly, the above detailed description should not be construed as limiting in all respects and should be considered illustrative. The scope of the various embodiments should be determined by a reasonable interpretation of the appended claims, and all changes within the equivalent scope of the various embodiments are included in the scope of the various embodiments. In addition, claims that do not have an explicit citation relationship in the claims may be combined to form an embodiment or may be included as new claims by amendment after filing.

Claims (5)

A first mixed extract obtained from a mixture composed of injin, chungho, geumjeoncho, and sanchija in a weight ratio of 2:2:1:1;
A second mixed extract obtained from a mixture composed of rhubarb, gold, tosaja, raw malt, eoseongcho, jeoryeong, uiyiin, and bokryeong in a weight ratio of 3:1:1:2:1:1:2:1; and
A third mixed extract obtained from a mixture consisting of cheonryeonja, mokhyang, humpak, yeonkyo and gyenaegeum; which is mixed,
A composition for treating and improving liver damage. delete According to claim 1,
The first mixed extract: the second mixed extract: the third mixed extract is mixed in a weight ratio of 4: 2: 1,
A composition for treating and improving liver damage. Comprising the composition of any one of claims 1 or 3,
A pharmaceutical composition for preventing and treating liver disease. Comprising the composition of any one of claims 1 or 3,
A food composition for preventing and improving liver disease.

Images