JP2007126410A - Herb composition for prevention and treatment of hepatic disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a herb composition effective for the prevention and treatment of hepatic diseases. <P>SOLUTION: The invention provides a combined herb composition comprising herbs of Artemisia capillaries Herba, Atractylodis Rhizoma Alba, Orostachydis Herba, Coriolus versicolo, and Polyporus umbellatus Pers., and additionally comprising at least one herb selected from group consisting of Angelica keiskei Herba, Alisma Rhizoma, Magnolia cortex, Licorice root, Zinger, Hoelen alba and Agaricus mushroom. The invention further provides methods of using the above crude drug composition and pharmaceutical composition as hepato-protective agent. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

The present invention relates to a herbal composition comprising Kawara mugwort medicinal herb, peanut herb, orostakis medicinal herb, kawaratake and choreimaitake herb extract and use of this herbal composition and medicinal composition as a hepatoprotective agent in accordance with the request for prevention and treatment of liver disease Regarding the method.

  Liver disease is currently present in various unfavorable environments such as pollutants, overdose, tobacco and other toxic substances, and also physiological stress that can be recovered by rest but is susceptible to other diseases such as immune system diseases It is one of the most common diseases in humans exposed to It has been reported that harmful substances such as carbon tetrachloride and D-galactosamine are harmful to the liver and kidney due to cell membrane damage. (Blue Car, JV, Fundamental and Applied Toxicology, Volume 6, pages 16-34, 1986).

  Several drugs derived from natural product resources having a free radical regeneration inhibiting action have been reported so far. For example, silymarin (SLD) isolated from the fruit of milk thistle belonging to the asteraceae family (SLD), BBD (biphenyldimethyldicarboxylic acid ester), a synthetic analog of mentor isolated from ginseng. (Caragy AB, Food Technolgy, 46, 65-68, 1992; Liang jun, Y. et al., Biochemistry and Biophysical Research Communication (Biochem. And Biophsy. Res. Comm.), 212, 360-366, 1995).

  However, there has been a demand for the development of an effective and safe drug for the treatment and prevention of liver diseases or improvement of liver function.

  Kawara mugwort medicinal herbs, sagebrush, etc., which belong to the Asteraceae family, include scoparon, chlorogenic acid, caffeic acid, pinene, capyrin, capyrene, couplerin, stearic acid, palmitic acid, etc., and treatment for jaundice and dermatitis has been reported Has been. Recently, an ethanol-soluble extract of this plant was reported to suppress liver damage and lipid peroxidation of hepatocytes. (Kimura, Y. et al., Chemical Pharm. Bull., 33 (5), 2028-2034, 1985).

  The rhododendron rhododendrons belonging to Asteraceae are reported to contain atractilon, atractilol, etc., and are used for the treatment of rheumatoid arthritis, diarrhea, anorexia and the like. It has long been used as a care product in China. (Chen, ZL et al., Planta Med, 53, 493, 1987; Chen, ZL et al., Phytochemistry, 45 (4), 765, 1997).

  Olostakis medicinal herbs, Aonooi Warengage, etc., which belong to the crested medicinal herb, belong to the crassulaceae family and have been used for the treatment of hemoptysis, malaria and the like.

  It has been reported that mushrooms of the mushroom belonging to the genus Sarnococcidae contain ergosterol, coriolan, krestin-D-glucan, teleholic acid and the like. Recently, it has been reported that this mushroom indirectly activates the immune mechanism and suppresses the growth of cancer cells. (Kim, B.K. et al., Singapore Archives, Pharmaceutical Research (Sing. Arch. Pharm. Res.), 2, 153, 1979).

It has been reported that mushroom choreimaitake belonging to the genus Sarnococcidae contains ergosterol, ergosta-4, 6, 8 (14), 22-tetraen-3-one, 2-hydroxytetracosanoic acid, bithion and the like. . Recently, it was reported that this mushroom has an anticancer activity, an antibacterial activity and an improvement effect on liver function. (Ha, YD et al., Korean J. Postharvest Sci. Technol., 8 (4), 481 (2001)).
Ashitaba medicinal herb, which is a cultivated medicinal herb belonging to the genus Angelica, has been reported to contain vitamins B1, B2, B6, B12, calcium, iron, phosphorus, etc., and is used to prevent diabetes, malaise, hypertension, etc. .
It has been reported that saximodaka rhizomes such as Aridaka, which belong to the family Omodaka, include Arisol A, B, Epialisol A, alkaloids, etc., and are used in the treatment of diarrhea, vomiting and the like.

Carraceae bark belonging to magnoliaceae, such as koboku and honoki, have been reported to contain magnolol, honokiol, magnoflorin, anonaine, essential oil, etc., and are used in the treatment of cough, stomach cancer, vomiting and the like.
It is reported that licorice, which is the root of the larva belonging to the leguminous family, contains some flavonoids such as triterpenoid saponins such as glycyrrhizin, liquiritin, neoliquiritin, neoisoliquiritin, etc., cough, stomach ulcer, hypertension, etc. Has been used in the treatment of.

Zinger, which is a ginger rhizome belonging to the ginger family, has been reported to contain gingivalol, gingiberene, ferrandolene, camphene, citral, linalool, methylheptenone, gingerol, etc., and used in the treatment of cough, stomach ulcer, hypertension, etc. Has been.
Bukryo, the white part of Matsuhodo belonging to the Sarnococcidae family, includes Pakiman, bucrylic acid, ergosterol, histidine, etc., and has been reported for use in the treatment of bacterial infections, anxiety, vomiting, and the like.

  Agaricus mushrooms in the whole agaric belonging to the agaric family are reported to contain cerevisterol, ergosterol, linoleic acid, oleic acid, stearic acid, chitin glucan, glucomannan, etc., such as cancer, hypertension, hypercholesterolemia, diabetes Has been used in therapy.

  However, no reports or disclosures have been made on any of the above-cited references regarding the combined therapeutic effects of the above herbal extracts on liver diseases. The above cited references are hereby incorporated herein by reference.

  Therefore, the present inventors tried to study the drug effect of the above-mentioned combined herbal extract in order to find an effective herbal formulation for enhancing the liver protective effect. It was found that the drug is effective in the treatment and prevention of liver diseases.

In one aspect, the present invention provides a pharmaceutical composition comprising a combined extract of herringworm herb, peanut, orostakis, herring and choreimaitake for prevention and treatment of liver disease.

The present invention also provides a pharmaceutical composition comprising, as an active ingredient, an effective amount for the prevention and treatment of liver disease, together with a pharmaceutically acceptable carrier.
The present invention also provides a method of treating liver disease by administering an effective amount of the above extract together with a pharmaceutically acceptable carrier to a mammal to protect the mammalian hepatocytes.
The present invention also provides the use of the above extract for drug formulation and manufacture for use in the treatment or prevention of human or mammalian liver disease.

  The present invention also includes, in combination with food-acceptable additives, an effective amount for the prevention and amelioration of liver disease, and the above extract for protecting and ameliorating liver disease as an active ingredient to protect hepatocytes. Provide health functional foods.

Detailed Description of the Invention

Accordingly, an object of the present invention is to extract a combined herb extract of Kawaramugi medicinal herb, peanut herb, orostakis medicinal herb, Kawaratake and Choreimaitake in an effective amount for the prevention and treatment of liver disease as an active ingredient together with a pharmaceutically acceptable carrier. It is providing the pharmaceutical composition containing an object.
The present invention also provides a combination of at least one medicinal herb selected from the group consisting of Ashitaba medicinal herb, Takusha, Koboku, licorice, Zinger, Bukkur, and Agaricus sp. A pharmaceutical composition comprising a herbal extract is provided.
Another object of the present invention is to provide the use of the above extract for the manufacture of a medicament for use in the treatment or prevention of liver disease in humans or mammals.

Another object of the present invention is to provide a method for treating liver disease in which an effective amount of the above extract is administered to a mammal together with a pharmaceutically acceptable carrier to protect the mammalian hepatocytes. .
The extract disclosed herein is composed of a combined drug extract, that is, Kawara mugwort medicinal herb, sand jellyfish, orostakis medicinal herb, Kawaratake and Choreimaitake, in the treatment or prevention of liver disease, and the mixing ratio (w / w) of each herb %) Is preferably 1-10: 1-10: 0.1-5: 0.5-5: 0.5-10, more preferably 1-5: 1-5: 0.5-3: 0 .5-3: 0.5-6.

  Further, the extract disclosed herein comprises a combined drug extract, i.e., Kawara mugwort medicinal herb, peanut jujube, orostakis medicinal herb, Kawaratake and Choreimaitake, in the treatment or prevention of liver disease, and Ashitaba medicinal herb, Takusha, Koboku, licorice, zinger , A herb extract to which at least one herb selected from the group consisting of Bud Ryu and Agaricus spp. Is added, and the mixing ratio (w / w%) of each herb is preferably 0.1-5: 1-10: 0.1-5: 0.1-5: 0.1-5: 0.1-5: 1-10, more preferably 0.5-3: 1-5: 0.5-3 : 0.5-3: 0.5-3: 0.5-3: 0.5-3, 0.5-3: 0.5-3: 0.5-3: 0.5-3: 1 -5.

  According to one aspect of the present invention, together with food-acceptable additives, the above extraction for protecting and ameliorating liver disease by protecting hepatocytes as an active ingredient in an amount effective for prevention and amelioration of liver disease Provide healthy functional raw foods including foods.

  The liver diseases disclosed herein are acute and chronic hepatitis, hepatomegaly, liver tumor, cirrhosis and liver cancer, preferably cirrhosis and hepatitis.

  The herbs that can be used in the present invention are apparent to those skilled in the art and consist of plants of the same genus that have been used for the same or similar purposes and can be replaced for the prevention and treatment of liver disease.

  The novel composition of the present invention is used in its ground form, extracted form therefrom, or dry extracted form therefrom.

The extracted crude drug composition is obtained by extraction with distilled water, lower alcohol such as methanol, ethanol or the like, or a mixture thereof, preferably water.
The pharmaceutical composition for treating liver disease can contain 0.01 to 95 w / w%, preferably 0.5 to 80 w / w% of the herbal composition of the present invention based on the total weight of the composition.
The novel herbal composition can be made according to the following preferred embodiments.
In the present invention, the herbal medicine composition is prepared by the following method. Wash and dry medicinal herbs, i.e. Kawara mugwort medicinal herbs, peanuts, orostakis medicinal herbs, Kawaratake and Choreimaitake, if necessary, Ashitaba medicinal herbs, taksya, koboku, licorice, zinger, bucuryo and agaricus moth, and dry them to the appropriate ratio (w / Mix in w). The mixture is pulverized to obtain a powdery herbal composition.

  The above crushed herbal composition is mixed with 5 to 20 times, preferably 10 to 15 times volume of distilled water, alcohol such as methanol, ethanol or a mixture thereof, preferably water or a mixture of ethanol and water, and the temperature is zero to Amplify at room temperature, preferably 4 to 6 ° C. for 12 to 48 hours, preferably 20 to 24 hours, or temperature 80 to 120 ° C., preferably 105 ° C. for 1 to 24 hours, preferably 2 to 5 During the time, the extract is refluxed by heating 2 to 5 times, or extracted by sonication, reflux or conventional extraction methods to obtain a water-soluble extractable herbal composition.

  Further, the herbal extract is filtered and concentrated at 80 to 90 ° C. under reduced pressure. The extract is concentrated by azeotropic distillation 1 to 5 times with 10 to 60 times the volume of water, and then freeze-dried or vacuum-dried to obtain a crude extract composition in a dry extract form.

  Another object of the present invention is to provide a preparation process of the above-described extract of the present invention for composition preparation effective for treatment and prevention of liver diseases.

  Still another object of the present invention is to provide a pharmaceutical composition comprising the herbal extract of the pulverized type, the extracted type or the dry extracted type obtained in the above step as an active ingredient for preventing and treating liver diseases.

  The novel composition of the present invention prepared in the above process significantly reduces the levels of glutamic acid oxaloacetic transaminase (GOT) and glutamic acid pyruvate transaminase (GPT) in the rat experimental model and suppresses liver fibrosis. In an oral acute toxicity study of this extract, this extract had no obvious effect on death counts, clinical signs, body weight changes and concluding observations on necropsy.

  A pharmaceutical composition for treating liver disease may contain about 0.01 to 95 w / w%, preferably 0.5 to 80 w / w% of the above herbal composition of the present invention based on the total weight of the composition.

  The present invention further provides an extract-containing hepatoprotective agent in an amount effective as an active ingredient for the prevention and treatment of liver diseases.

  The present invention further provides the use of novel extracts for drug formulation, such as hepatoprotective drugs, in the prevention and treatment of liver diseases.

  The present invention further provides a method for treating liver disease in mammals comprising administering to the mammal an effective amount of a herbal composition and a pharmaceutically acceptable carrier thereof.

  The new composition may further contain conventional carriers, adjuvants or diluents according to the usage. This carrier is preferably used according to its usage, but is not limited. Suitable diluents are listed in the text of Remington's Pharmaceutical Science (Mack Publishing Co., Easton, PA).

In the following, the following blending methods and shaped are merely exemplary and are in no way limiting on the present invention.
The herbal composition according to the present invention comprises a pharmaceutically acceptable carrier, excipient or diluent such as lactic acid, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, A pharmaceutical composition containing calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, benzoic acid methyl hydroxy ester, benzoic acid propyl hydroxy ester, talc, magnesium stearate and mineral oil can be provided. The formulation can further contain fillers, anti-agglomerating agents, lubricants, wetting agents, flavoring agents, emulsifying agents, preservatives and the like. The compositions of the invention are formulated so that the active ingredient can be released rapidly, sustained or delayed after administration to a patient using any method known in the art.

  For example, the composition of the present invention can be dissolved in oil, propylene glycol or other solvents that are commonly used for injection. Suitable examples of the carrier include, but are not limited to, physiological saline, polyethylene glycol, ethanol, vegetable oil, and isopropyl myristate. For topical administration, the compounds of the invention can be formulated in the form of ointments and creams.

  Pharmaceutical formulations containing herbal medicines are oral dosage forms (powder, tablets, capsules, soft capsules, water-soluble drugs, syrups, elixir tablets, powders, sachets, granules) or topical preparations (creams, ointments, liquid medicines, gels, fragrances) Ointments, patches, pastes, spray solutions, aerosols, etc.), suppositories or sterile injectable preparations (solutions, suspensions, emulsions).

  The pharmaceutical dosage forms of the herbal composition of the present invention can be used not only in the form of a pharmaceutically acceptable salt, but can be used alone or in combination with other pharmaceutically active compounds as well as appropriate related substances.

  The desired dose of the new composition will vary depending on the subject's condition and weight, drug form, route of administration and duration, and can be selected by one skilled in the art. However, to obtain the desired effect, it is usually recommended to administer the novel composition of the present invention in an amount in the range of 0.01-10 g / kg, preferably 1-5 g / kg per day. The dose can be administered once or multiple times per day. With respect to composition, the herbal composition comprises between 0.01 and 80% by weight, preferably 0.5 to 50% by weight, based on the total weight of the composition.

  The pharmaceutical composition of the present invention can be administered to a subject animal such as a mammal (rat, mouse, domestic animal or human) by various means. Any dosage form is contemplated. For example, it can be administered by oral, rectal, intravenous, intramuscular, subcutaneous, intradermal, intrameningeal, epidural or intracerebroventricular injection.

  According to one aspect of the present invention, hepatocytes are protected with an active ingredient in an amount effective for prevention and improvement of liver disease, and together with food-acceptable additives, the above extract for protection and improvement of liver disease A health functional food product is provided.

  The herbal medicine composition of the new health functional food is used in its powder form, extracted form or dried extract form.

  The composition of the health functional food for prevention and improvement of gastrointestinal dysfunction may contain about 0.01 to 95 w / w%, preferably 0.5 to 80 w / w% of the herbal composition based on the total weight of the composition.

  The herbal composition can be added to foods, additives or beverages for prevention and improvement of gastrointestinal dysfunction. For the purpose of preventing and improving gastrointestinal dysfunction, the amount of the herbal medicine in the food or beverage is about 0.1 to 15 w / w%, preferably 1 to 10 w / w% of the total food weight for the health food composition. The range is 1 to 30 g, preferably 3 to 10 g, per 100 ml of the health drink composition.

  As long as the health drink composition of the present invention contains the herbal medicine composition as an indispensable component in the indicated ratio, there is no particular limitation on other liquid components in which other components are various deodorizers or natural carbohydrates as in conventional beverages. Examples of the aforementioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, conventional sugars such as dextrin and cyclodextrin, sugar alcohols such as xylitol, and erythritol. As deodorants other than those mentioned above, natural deodorants such as thaumatin, stevia extracts such as rebaudioside A, glycyrrhizin, and synthetic deodorants such as saccharin and aspartame are preferably used. The amount of said natural carbohydrate is generally in the range of about 1 to 20 g, preferably 5 to 12 g per 100 ml ratio of the beverage composition.

  Ingredients other than those described above include various nutrients, vitamins, minerals or electrolytes, synthetic flavors, colorants and improvers in the case of chocolate and cheese, pectinic acid and its salts, alginic acid and its salts, organic acids, protection Colloid adhesives, pH control agents, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like. Ingredients other than those described above are fruit juice for producing natural fruit juice, fruit juice drinks and vegetable drinks, and the ingredients can be used independently or in combination. The component ratio is not so important, but is usually in the range of about 0 to 20 w / w% per 100 w / w% of the component.

Examples of the foods that can be added to the herbal medicine composition include various foods, beverages, gums, complex vitamins, health improving foods, and the like.
It will be apparent to those skilled in the art that various modifications and variations can be made in the composition, use and preparation of the present invention without departing from the spirit or scope of the invention.

The following examples and experimental examples are intended to further illustrate the present invention without limiting the scope.

Combined prescription (MC) preparation 2g Kawaramugi medicinal herb purchased at Gyeongdong market in Seoul, 1.7g pea jelly, 1g orostakis medicinal herb, 0.7g Kawaratake and 1g choreimaitake, and 10 times the weight of this herb Water was added. The solution was allowed to stand for 12 hours, and the first reflux extraction was performed at 105 ° C. for 2 hours under vacuum. The extract obtained in the first round was filtered and the product residue was subjected to a second reflux extraction under vacuum. The extract was filtered through a filter sieve (Model No. 140, 106 μm) and each filtered extract was collected. The collected filtrate was subjected to reflux filtration at 80-90 ° C. until the final volume of the extract reached about 1 liter and the specific gravity of the extract was about 1.2 to 1.3 (Brix, over 60). The extract was dried at 60 ° C. with a hot air dryer until the water content was 5% or less, the dried solid was crushed, and filtered through a filter medium (number 50, 300 μm) to obtain a new powder extract (hereinafter referred to as MC). Obtained.

Compound Formula (AC) Formulation 2g Kawara Momogi herb purchased at Gyeongdong Market in Seoul, 1.7g peanut, 1g Olostakis herb, 0.7g Kawaratake, 1g choreimaitake, 0.7g Ashitaba medicinal herb, 1.7g Takusha, 0 .7 g, licorice 0.5 g, zinger 0.3 g, buccal 0.7 g and agaricus koji 1.3 g were washed and reflux extraction similar to Example 1 was performed to obtain a new powder extract (hereinafter referred to as AC). It was.

Experimental Example 1

Effects on chronic liver damage induced by carbon tetrachloride in a rat model In order to examine the inhibitory effect on liver damage of the novel extract obtained in the example, the following experiment was performed by the following method.

1-1 Reagents and experimental animals Carbon tetrachloride (Sigma Co.), olive oil (Sigma Co.), alanine aminotransferase (ALT, GPT, Standby Bio (Stanbio) Co.)) and aspartate aminotransferase (AST, GOT, Stanbio Co.) were purchased from a commercial company for use in experiments.
Male Sprague Dawley rats weighing approximately 200 g were used in the experiments and allowed access to food (Harlan Teklad, USA) and water. All animals were maintained in a controlled environment with a temperature of 21-24 ° C., humidity of 60-80%, and a light / dark cycle of 12 hours for at least one week prior to use.

1-2 . Effect on carbon tetrachloride chronic liver injury Each experimental rat was given a mixed solution of olive oil and carbon tetrachloride (1: 1) at a dose of 1.0 mg / kg for 3 days to evaluate the effect on liver injury. Acute hepatotoxicity was induced by intraperitoneal administration. One hour later, extracts of various concentrations suspended in 1% CMC (carboxymethylcellulose), ie, 6 mg / kg, 30 mg / kg and 60 mg / kg were orally administered to rats as test groups for 4 days, and the same amount of physiological saline Only water was treated as a negative control. On the last day of the test, 1.5 ml of blood was stored from anesthetized experimental animals and fixed by reperfusion. Blood samples were centrifuged at 3000 rpm for 20 minutes, and each GOT and GPT level of each sample was determined using a CH100 + apparatus (SEAC Co.). The test group and test process are shown in Table 1 below.
Table 1

As can be seen in FIGS. 1a and 1b, treatment examples with the novel extract obtained in Example 1 (HA-MC group) are particularly dependent on liver-damaged rats at doses of 30 mg / kg and 60 mg / kg. The model significantly suppressed GOT and GPT levels (P <0.05 ^* , P <0.01 ^** ). As can further be seen in FIGS. 2a and 2b, the treatment with the novel extract obtained in Example 2 (HA-AC group) is particularly in the whole dosage range, ie 12 mg / kg, 60 mg / kg and 120 mg / kg. GOT and GPT levels in the rat model of liver injury were significantly suppressed in a dose-dependent manner at kg (P <0.05 ^* , P <0.01 ^** ).
Therefore, it was confirmed that the novel extract of the present invention is effective in alleviating liver function.

Experimental Example 2

Effect on inhibition of collagen distribution and GOT and GPT levels in rat model In order to examine the cirrhosis improving effect of the novel extract obtained in the example, the following experiment was performed by the following method.

2-1 Reagents and experimental animals
DMN (dimethylnitrosamine, Sigma Co.), alanine amino group transferase (ALT, GPT, Stanbio Co.) and aspartate amino group transferase (AST, GOT, Stanbio) Co.)) was purchased from a commercial company for use in experiments.

  Wistar rats weighing approximately 270 g were used in the experiments and allowed access to food (Harlan Teklad, USA) and water. All animals were maintained in a controlled environment with a temperature of 21-24 ° C., humidity of 60-80%, and a light / dark cycle of 12 hours prior to use for at least one week.

Effect on collagen distribution and inhibitory effect on GOT and GPT In order to evaluate the effect on cirrhosis, 1% DMN was intraperitoneally administered to each experimental rat at a dose of 10 μg / kg / day for 3 days to induce cirrhosis. . 30 mg / kg / day of extract MC and 60 mg / kg / day of AC extract were orally administered to the test group rats for 4 weeks, and only the same amount of physiological saline was treated as a negative control. On the last day of the test, 1.5 ml of blood was stored from anesthetized experimental animals and fixed by reperfusion. Blood samples were centrifuged at 3000 rpm for 20 minutes, and each GOT and GPT level of each sample was determined using a CH100 + apparatus (SEAC Co.) as shown in FIGS. 3a and 3b.

In order to examine the collagen distribution in the liver tissue, Masson's triple staining method that stains only the collagen part is used, and the isolated liver tissue is embedded with an automatic tissue analyzer (Citadel 2000, Shandon Co.). The slices were sliced into 4 μm wide pieces with a tissue microtome (Leica RM2145). Five lesions were selected for each tissue, and the fibrin ratio of the lesions was determined by an image analysis system. The average value of this ratio was calculated and converted to collagen content. (See FIG. 4).
As can be seen in FIG. 4, a liver extract rat model was obtained in the novel extract obtained in Example 1 (HA-MC group) and also in the treatment group with the novel extract obtained in Example 2 (HA-AC group). GOT and GPT levels were significantly suppressed in a dose-dependent manner. Furthermore, the collagen amount of the treated group of the novel extract obtained in Examples 1 and 2 was 1.21 and 1.05, respectively, while the control group and the normal group were 2.93 and 0.53, respectively.

  Therefore, it was confirmed that the novel extract of the present invention is remarkably effective in suppressing the progression of cirrhosis.

Experimental Example 3

Assessment of acute toxicity To investigate the toxicity of the new extract, an acute toxicity test was conducted on rats.
Fifteen male and female SD rats were divided into three groups, and the new extract was administered to three rats at three doses, namely 1 g / kg, 2 g / kg and 5 g / kg for 14 days, and the control group was water Was processed. Toxicity signs such as body weight changes, blood analysis and histology were observed for 4 weeks.
As a result of the experiment, there was no death in rats administered with the new extract, and there was no significant abnormality in weight increase, histological examination and the like. This result confirmed that the new extracts, namely HA-MC and HA-AC, are safe.

Hereinafter, although the compounding method and kind of an excipient | filler are demonstrated, this invention is not limited to these. A typical formulation example is described below.
Injection formulation HA-MC 100mg
Sodium metabisulfite 3.0mg
Methylparaben 0.8mg
Propylparaben 0.1mg
Distilled water for injection An appropriate amount of the injection preparation was prepared by dissolving the active ingredient while controlling the pH to 7.5, filling all the ingredients into a 2 ml ampoule, and sterilizing by a conventional injection preparation method.
Powder formulation HA-MC 500mg
Cornstarch 100mg
Lactose 100mg
Talc 10mg
The powder preparation was prepared by mixing the above ingredients and placing them in a sealed package.
Tablet formulation HA-AC 200mg
Cornstarch 100mg
Lactose 100mg
Magnesium stearate Appropriate amount of tablets was prepared by mixing the above ingredients into tablets.
Capsule formulation HA-MC 100mg
Lactose 50mg
Cornstarch 50mg
Talc 2mg
Magnesium stearate An appropriate amount of tablets was prepared by mixing the above ingredients and filling gelatin capsules by a conventional gelatin preparation method.
Liquid formulation HA-AC 1000mg
20g sugar
20g polysaccharide
Lemon flavor 20g
The liquid formulation was prepared by dissolving the active ingredients, filling all components to 1000 ml ampoules and sterilizing by the conventional liquid formulation method.
Health food formulation HA-MC 1000mg
Vitamin mixture appropriate amount Vitamin A acetate 70μg
Vitamin E 1.0mg
Vitamin B ₁ 0.13mg
Vitamin B ₂ 0.15mg
Vitamin B ₆ 0.5mg
Vitamin B ₁₂ 0.2μg
Vitamin C 10mg
Biotin 10 μg
Nicotinamide 1.7mg
50 μg of folic acid
Calcium pantothenate 0.5mg
Mineral mixture appropriate amount Ferrous sulfate 1.75mg
Zinc oxide 0.82mg
Magnesium carbonate 25.3mg
Monopotassium phosphate 15mg
Dicalcium phosphate 55mg
Potassium citrate 90mg
Calcium carbonate 100mg
Magnesium chloride 24.8mg
The vitamin and mineral mixture described above can be varied. Such modifications are not considered as departing from the spirit and scope of the present invention.
Health drink formulation HA-AC 1000mg
Citric acid 1000mg
Oligosaccharide 100g
Apricot concentrate 2g
Taurine 1g
900ml distilled water
The health drink was prepared by dissolving the above ingredients, mixing, stirring at 85 ° C. for 1 hour, filtering, then filling all the ingredients into a 1000 ml ampoule and sterilizing by the conventional health drink formula.
It will be apparent that the present invention can be varied in many ways as described. Such modifications are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications will be apparent to those skilled in the art and are intended to be included within the scope of the following claims.

As described in the present invention, the combined herb composition exhibits a strong protective activity on liver function, suppresses increases in GOT and GPT levels, and prevents cirrhosis.
The novel composition of the present invention is useful for the prevention and treatment of liver diseases and can be used as a safe and effective hepatoprotective drug.

The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description in conjunction with the accompanying drawings.
The dose-dependent effect on serum GOT results (1a) and GPT results (1b) in carbon tetrachloride-induced rats by the product extract of Example 1 is shown. The dose-dependent effect on serum GOT results (2a) and GPT results (2b) in carbon tetrachloride-induced rats by the product extract of Example 2 is shown. The inhibitory effect on the serum GOT result (3a) and the GPT result (3b) in the cirrhosis induction rat by the product extract of an Example is shown. The effect on the collagen distribution of the liver tissue by the product extract of an Example is represented.

Claims (14)

A pharmaceutical composition comprising a combined herb extract comprising Kawara mugi medicinal herb, peony herb, orostaki medicinal herb, kawaratake and choreimaitake, in an effective amount and active ingredient for the prevention and treatment of liver disease, together with a pharmaceutically acceptable carrier . This pharmaceutical composition has a mixing ratio (w / w%) of Kawara mugwort medicinal herb, peanut, orostakis medicinal herb, Kawaratake and Choreimaitake on a dry weight basis of each medicinal herb 1-10: 1-1-10: 0.1-5: 0. The pharmaceutical composition according to claim 1, which is in the range of 5-5: 0.5-5. In addition to the combined herb shown in claim 1 for the prevention and treatment of liver disease, this herb contains at least one medicinal herb selected from the group consisting of Ashitaba medicinal herb, Takusha, Koboku, licorice, Zinger, Bukkur and Agaricus spp. The pharmaceutical composition of claim 1. At least one medicinal herb selected from the group consisting of Ashitaba medicinal herb, takusha, koboku, licorice, zinger, bukuryo, and agaricus koji has a mixing ratio (w / w%) based on the dry weight of each medicinal herb. The pharmaceutical composition according to claim 3, which is in the range of 5: 1-10: 0.1-5: 0.1-5: 0.1-5: 0.1-5: 1-10. The pharmaceutical composition according to any one of claims 1 to 4, wherein the crude drug composition is used in its powder form, extracted form or dried extract form, The pharmaceutical composition according to claim 1 or 3, wherein the extraction solvent is selected from the group consisting of distilled water, lower alcohols and mixtures thereof. The pharmaceutical composition according to claim 1 or 3, wherein the herbal composition is about 0.01 to 95 w / w% of the total weight of the composition. The pharmaceutical composition according to any one of claims 1 to 4, wherein the liver disease is acute or chronic hepatitis, hepatomegaly, liver tumor, cirrhosis or liver cancer. Any one of claims 1 to 4 wherein the pharmaceutical composition is provided by an acceptable carrier in powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, topical drugs, suppositories or sterile injections. Pharmaceutical composition. In the preparation process of the pharmaceutical composition according to any one of claims 1 to 4, the herbs are washed, dried and mixed in an appropriate ratio (w / w), or additional herbs are separately mixed in the herbal composition preparation stage, Pulverize and mix the pulverized composition with 5 times the amount of distilled water, alcohol such as methanol, ethanol, etc., or mixtures thereof, and unflag for 12 hours to 48 hours at a temperature between zero and room temperature, or at a temperature of 80 Heat 2 to 5 times in the range 1 to 24 hours at 1 to 100 ° C., filter the extract and concentrate at 80 to 90 ° C. under reduced pressure, 1 to 5 times azeotropic distillation with 10 to 60 times volume of water And then drying by freeze drying or vacuum drying to obtain a herbal composition in a dry extract form. Effective in preventing and ameliorating liver disease, active ingredients, and food-acceptable additives, and protecting hepatocytes to prevent or ameliorate liver disease, Kawaramugi medicinal herb, peanut, orostakis medicinal herb, Kawaratake and Choreimaitake Health functional food consisting of a combined herbal extract consisting of The health functional food according to claim 11, wherein the medicinal herb contains at least one medicinal herb selected from the group consisting of Ashitaba medicinal herb, takusha, koboku, licorice, zinger, bukkuri and agaricus koji in addition to the combined medicinal herb shown in claim 11. The health functional food according to claim 11 or 12, wherein the crude drug composition is used in a powder form, an extracted form or a dried extract form. The health functional food according to claim 11 or 12, wherein the health functional food is provided in the form of powder, granule, capsule or beverage.

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