KR20010086667A - Pharmaceutical composition for the prevention and treatment of hepatocirrhosis - Google Patents

Abstract

PURPOSE: Provided is a novel pharmaceutical composition which shows excellent treatment and prevention effects of hepatocirrhosis without toxicity and pharmaceutical stability. CONSTITUTION: The pharmaceutical composition comprises larvae of Holotrichia diomphalia Bates(scarabaeidae); and fruits of Gardenia jasminoides Ellis, Scutellaria baicalensis Georgi(Labiatae) and dried roots of Bupleurum falcatum Linne(Umbelliferae), in particular, in a weight ratio of 0.7-1.5 : 1-2 : 1 : 1-2. The composition can be used in an amount of 15 to 300mg and administered in formulation types of tablet, powder, granule, solution, syrup or capsule. The composition is prepared by following steps of: mixing the active ingredients, and then extracting with organic solvents while refluxing; filtering the extract to obtain filtrate; further extracting and filtrating twice the residue to obtain further filtrate; combining the filtrates; concentrating under pressure to prepare the extracts; and adding a pharmaceutical acceptable carrier to the extracts to form the formulation in a desired type.

Description

PHARMACEUTICAL COMPOSITION FOR THE PREVENTION AND TREATMENT OF HEPATOCIRRHOSIS}

The present invention is prepared with a prophylactic and therapeutic effect on cirrhosis ( The present invention relates to a novel pharmaceutical composition for preventing and treating cirrhosis of the liver, including Gardenia jasminoides, Gold, and Siho.

Liver cirrhosis (hepatocirrhosis) is a disease in which the liver hardens and shrinks due to disorders of the parenchymal cells of the liver and proliferation of connective tissue.It is caused by alcoholic beverages, nutritional deficiencies, and parasites. Anemia, jaundice, edema, and general weakness will appear.

Animal herbal manufacture with pahyeol the conventional shot, hanger, sangyeol and tongyu action [gold slugs (Holotrichia diomphalia larvae of Bates and closely related insects (gumbengyigwa scarabaeidae)]; Gardenia with cheongyeol reconciliation, yanghyeol detoxification [(Gardenia Gardenia fruit of jasminoides Ellis or other cognates ( Cucanus Rubiaceae ); golden with decay, diuresis, antibacterial, antiviral, antifungal, soothing, lowering blood pressure, rising blood sugar, diarrhea [ Carrot and Labiatae] Botanical herbal medicines, such as roots peeled off], are herbal medicines that have been used for liver disease as a single ingredient.

In addition, the herbal medicine Shiho (dried roots of Bupleurum falcatum Linne) has been widely used for pleurisy and chest pain due to antipyretic and analgesic effects.

However, although the herbal medicines such as gardenia, gold and shiho are among these herbal medicines, the herbal medicines with safety have been secured, but the production of slug larvae has been reported to be highly toxic. In experiments on the effects of hepatic impairment [Journal of Pharmacognosy, 22 (1), 36-44 (1991)], the aqueous ethanol extract of the preparation had an effect on carbon tetrachloride-induced hepatic impairment. It has been reported that a toxicity of up to 10 mortality was recognized at 1,000 mg / kg / kg and intraperitoneal administration.

Therefore, in the present invention, in order to remove such toxic substances first, the numerical value was first determined based on the numerical method currently available in the traditional Chinese medicine, and then the prescription of the remaining three herbal medicines was based on the herbal medicine.

In other words, these four herbal medicines (manufacture, gardenia, gold and Siho) are selected, washed, cut, sterilized and dried. According to various X manufacturing methods, extracts of complex preparations were prepared and tested for efficacy and toxicity tests for liver disease with a certain amount of X. As a result, it was found that there was no toxicity and had an excellent effect on the treatment and prevention of cirrhosis of the liver. This invention was completed.

Therefore, the present invention is to provide a novel pharmaceutical composition having a treatment and prevention effect of the new liver cirrhosis is less toxic or side effects than the slug single or silymarin single formulation and excellent in terms of effectiveness.

1 is a graph showing the effect of the composition according to the invention on serum biochemical markers in biliary ligated rats,

Figure 2 is a graph showing the effect of the composition according to the invention on the amount of hydroxyproline (hydroxyproline) in liver tissue in biliary ligated rats.

The pharmaceutical composition for preventing and treating liver cirrhosis of the present invention contains the preparation of animal herbal medicine and the gardenia herb gardenia, gold and shiho, and specifically, the ratio of the manufacture, gardenia, gold and shiho is 0.7-1.5: 1 to 1-2. It is a pharmaceutical composition for liver cirrhosis prevention and treatment which is contained in the weight ratio of 1: 1-2.

In the manufacturing method of the pharmaceutical composition of the present invention, after the numerical processing of the preparation, gardenia, gold and shiho, respectively, they are mixed by a predetermined amount, extracted with an organic solvent, and then obtained under reduced pressure and concentration to obtain a pharmaceutically acceptable carrier for each formulation. It is formulated by adding.

First of all, the production of strong toxic effects is carried out by the method already established by the emulsification method, that is, 1) removing mud from the sieve and washing it to dry in the daylight (brain poszaron), or 2) glutinous rice after drying. Roast until it turns black, and remove hair growth around the mouth and body, cut into 3-4 pieces (agreement, medical introduction), or 3) put it in hot water, wash it with purified water, and dry it in daylight. One of the animal animal medicines was selected and quantitatively prepared into powder or cut by adjustment.

Gardenia, Golden and Siho are each selected by washing, drying, cutting and sterilization of commercially available herbal medicines, and then powdered or adjusted to prepare each herbal medicine as a pharmaceutical.

These preparations, gardenia, golden and wild medicinal herbs were mixed at a weight ratio of 0.7 to 1.5: 1 to 2: 1: 1 to 2, and then extracted using various extracting organic solvents. The extraction solvent was extracted three times using organic solvents such as 70 saturated ethanol, ethanol, methanol, and ethyl acetate, and the extracts were combined to prepare X using lyophilization or reduced pressure rotary concentrator. The extracted extract was found to have a good yield, the best effect on liver cirrhosis, and no toxicity at all. This fraction was used as an active ingredient for preventing and treating liver cirrhosis. In the present invention, when the mixing ratio is 0.7 or less, the effect on the treatment of liver disease is questioned, and when 1.5 or more, toxic expression is concerned. Gardenia, Golden, and Shiho Herbal Medicines were also preferred in terms of efficacy and preparation in the above ratio within the range of the dosage.

Furthermore, the pharmacological effect determination experiment of the pharmaceutical composition according to the present invention was carried out. The 70-saturated ethanol extract extract prepared in the present invention was induced by cirrhosis according to the method of Kotaras et al. (1984) for 16 hours. During the fasting, the rats were orally administered to each group for 4 weeks (28 days), once daily, 50 mg / kg and 25 mg, respectively.

As a result, the survival rate () was 100 for the Sham group, about 62 for the control group, 56 for the silymarin test group, and 63 for the manufacturing monolith (S) group, in particular, according to the present invention. In the (S-1) experimental group, the survival rate was higher than that of the silymarin test group at 42 and 25 mg / kg when administered at 50 mg / kg.

In the experimental group (S-2), when the 50 mg / kg per body weight was administered, 67, and when the 25 mg / kg was administered, the survival rate was higher than that of the silymarin (Silymarin) or manufacturing single (S) experimental group.

In the single-dose toxicity test using SD rats, the toxicity was not more than 5 g / kg. Serum biochemical markers (ALT, AST and ALP) levels confirming the scale of liver disease were included in the control group. The biliary ligation test group increased significantly compared to the Sham group.

ALT (alanine aminotransferase) significantly decreased to 55, 54 and 50 mg / kg doses at 54 and 59 at 25 mg / kg doses of experimental groups S-1 and S-2, respectively, and to S (aspartate aminotransferase) at AST (aspartate aminotransferase). -1 and S-2 significantly decreased from 25 mg / kg dose to 38 and 52 and 37 and 46 in 50 mg / kg dose group, respectively.

Alkaline phosphatase (ALP) significantly decreased from 25 mg / kg doses to 30 and 38 and 50 mg / kg doses to 24 and 28, respectively, and the amount of hydroxypurine (Hydroxyproline) was decreased. Compared with the control group, the experimental groups S-1 and S-2 were significantly reduced from 25, 45, 39 and 50 mg / kg doses to 38 and 32, respectively.

From these experimental results, the experimental groups showed better effects than silymarin or a single product of manufacture, and thus, it can be said that the treatment effect for cirrhosis is excellent.

The pharmaceutical composition of the present invention can be used alone, 70 hydrous ethanol extract extract, methanol extract extract and ethyl acetate extract extract in the extract extract, the formulations are tablets, powders, granules, It can be prepared by using a liquid, syrup, capsule, or the like.

In the pharmaceutical composition of the present invention, it is preferable that the general adult divides the amount of 15 to 300 mg once or several times a day.

Hereinafter, the present invention will be described in detail through Examples and Experimental Examples, and the present invention is not limited to these Experimental Examples and Examples.

(Reference Example 1)

Preparation of 70 hydrous ethanol extract extract (S) from the production (slugs)

100 g of 70 g of ethanol was added to the mixture, and the mixture was heated and extracted for 6-8 hours in a reflux extractor, filtered, and 500 ml of 70 hydrated ethanol was added to the residue. The extraction was repeated three times, and the extract was extracted and combined with a pre-extracted extract.

(Example 1)

Preparation of composite extract extract (S-1)

190 g of commercially produced (Golden slug), 270 g of Gardenia jasmine, 270 g of Gold, 270 g of Siho were mixed and adjusted, and 3 liters of 70 hydrated ethanol were added and heated and extracted for 6-8 hours in a reflux extractor. The extract is then cooled and filtered. In the same way, the extract obtained by two additional extractions was combined with the extract, and then concentrated under reduced pressure at 40 ° C. in a vacuum condenser to obtain 350 g (yield of 0.7: 1: 1: 1 ratio of Manufacture, Gardenia, Golden and Siho) 350 g (yield 35) Got.

(Example 2)

Preparation of composite containing extract extract (S-2)

250 g of commercially produced (gold slug), 250 g of gardenia, 168 g of gold, and 332 g of shiho were each adjusted and mixed, followed by 3 liters of 70 hydrous ethanol, which was heated and extracted for 6-8 hours in a reflux extractor. The extract is then cooled and filtered. In the same way, the extract obtained by two additional extractions was combined with the extract, and then concentrated under reduced pressure at 40 ° C. in a vacuum condenser to obtain 340 g (yield: 1.5: 1.5: 1: 2 ratio of manufacturing, gardenia, gold and shiho) (yield 34). Got.

(Example 3)

Preparation of composite containing extract extract (S-3)

Commercially purchased (Golden slugs) 190 g, Gardenia 270 g, Golden 270 g, Shiho 270 g were mixed and adjusted, and 3 liters of methanol was added thereto. The mixture was heated and extracted for 6-8 hours in a reflux extractor, followed by extraction. After cooling, it is filtered. In the same way, the extract obtained by two additional extractions was combined with the extract, and then concentrated under reduced pressure at 40 ° C. in a vacuum condenser to obtain a ratio of 0.7: 1: 1: 1 in manufacturing, gardenia, gold and shiho 360 g (yield 36 )

(Example 4)

Preparation of composite extract extract (S-4)

250 g of commercially produced (gold slugs), 250 g of gardenia, 168 g of gold, 332 g of shiho were each adjusted and mixed, and then 3 liters of ethanol was added and heated and extracted in a reflux extractor for 6 to 8 hours. After cooling, it is filtered. In the same way, the extract obtained by two additional extractions was combined with the extract, and then concentrated under reduced pressure at 40 ° C. in a vacuum condenser to obtain 350 g (yield of 1.5: 1.5: 1: 2 of manufacturing, gardenia, gold and shiho) (yield 35 )

(Example 5)

Preparation of composite extract extract (S-5)

190 g of commercially produced (gold slugs), 270 g of gardenia, 270 g of gold, 270 g of shiho were each adjusted and mixed, 3 liters of ethyl acetate was added, heated and extracted with a reflux extractor for 6-8 hours. The extract is cooled and then filtered. In the same way, the extract obtained by two additional extractions was combined with the extract, and then concentrated under reduced pressure at 40 ° C. in a vacuum condenser to obtain 170 g (yield of 0.7: 1: 1: 1 ratio of Manufacture, Gardenia, Gold and Siho) (yield 17 )

(Example 6)

Preparation of composite extract extract (S-6)

250 g of commercially produced (gold slugs), 250 g of gardenia, 168 g of gold, 332 g of shiho were each adjusted and mixed, 3 liters of ethyl acetate was added, heated and extracted with a reflux extractor for 6-8 hours. The extract is cooled and then filtered. In the same way, the extract obtained by two additional extractions was combined with the extract, and then concentrated under reduced pressure at 40 ° C. in a vacuum condenser to obtain 160 g (yield of 1.5: 1.5: 1: 2 of manufacturing, gardenia, gold and shiho). )

(Composition Example 1)

Solution

-In 500 ml

<Example 1> or 150 mg of extracts containing the preparation of <Example 2>

Isomerized sugar 55 g

L-sodium glutamate 3.4 g

Phosphoric Acid 1.5 g

Herb Essence

0.5 g sodium benzoate

0.5 g of sodium dehydroacetate

Tablet quantity

After dissolving isomerized sugar, sodium benzoate and sodium dehydroacetate in a predetermined amount of purified water, and adding the extract extract of the composite containing Preparation of Example 1 or 2 to make a homogeneous solution, sodium glutamate and phosphoric acid, flavoring, flavoring Add to mix. After the final volume was applied to 500 ml, the filtrate was filtered and the filtrate was filled in bottles by the usual method and sterilized to prepare a liquid solution containing 15 mg of the preparation-containing complex extract X per bottle.

(Composition Example 2)

Granules

-In 300 g

<Example 1> or 1.5 g of the extract containing the preparation of <Example 2>

240 g lactose

45 g of caramel powder

1.5 g of hydroxypropyl cellulose

Purified water

1) First, 240 g of lactose and 45 g of caramel powder are stirred and mixed evenly.

2) 1.5 g of pre-hydroxypropyl cellulose (HPC) was added to 30 ml of ethanol and completely dissolved. Then, 1.5 g of the extract of the composite containing the preparation of <Example 1> or <Example 2> was added to this solution, and gradually 1 Stir homogeneously for hours.

3) To the mixed powder prepared in advance in the above 1) was slowly added while stirring the main chemical solution of 2), mixed until homogenized, and then added by adding a suitable amount of purified water, homogenized again, and then the preparation of the pharmacopoeia granules According to the method, granules were prepared such that 15 mg of the extract-containing complex extract was contained in 1 sachet (3 g).

(Composition Example 3)

refine

A tablet containing 15 mg of the extract containing the composite preparation was prepared by compression molding the granules prepared in Composition Example 2 per 1000 mg.

Experimental Example 1

Stability test according to the change over time of the composition (granule) containing the extract extract

1. Sample

The granular composition containing the preparation-containing complex extract extract prepared according to Example 1 was tested as a specimen.

2. Experimental method

1) Appearance

It was visually confirmed.

2) Confirmation test

When tested according to the quantitative method, the sample solution was confirmed to show a peak at the same retention time as the standard solution.

3) According to the herbal medicine test method of the general test method of the pharmacopeias.

4) Content test

The content of Baicalin in Composition Example 2 (granule) was analyzed by high performance liquid chromatography.

5) Preservation of Specimen

Sample preservation was tested at 40 ° C. (relative humidity 75) at room temperature and in LifeTesta.

3. Experimental Results

Each experimental data was the average of the results of three or more experiments (Table 1).

Table 1

Stability test (acceleration test) according to change of composition example 2 (granule) with time

Manufacturing number Storage condition item period Room temperature Manufacturing number Storage condition item period 40 ° C., 75 R.H. Constellation Confirm Ash () baicalin content Constellation Confirm Ash () baicalin content Pilot1 Start fitness positivity 3.29 99.87 Pilot1 Start fitness positivity 3.28 99.84 2 months 3.30 99.86 2 months 3.24 99.87 4 months 3.28 99.84 4 months 3.25 99.68 6 months 3.26 98.82 6 months 3.26 98.25 Pilot2 Start fitness positivity 3.25 99.80 Pilot2 Start fitness positivity 3.22 99.84 2 months 3.28 99.82 2 months 3.21 99.23 4 months 3.23 99.84 4 months 3.26 99.21 6 months 3.21 98.73 6 months 3.24 97.98 Pilot3 Start fitness positivity 3.26 99.92 Pilot3 Start fitness positivity 3.28 99.84 2 months 3.30 99.90 2 months 3.23 99.32 4 months 3.27 99.84 4 months 3.24 99.34 6 months 3.29 98.74 6 months 3.22 97.32

Experimental Example 2

Stability test according to the change over time of the composition (granule) containing the extract extract

1. Sample

The granular composition containing the extract containing the preparation containing the preparation prepared in Example 2 was tested as a sample.

2. Experimental method

1) Appearance

It was visually confirmed.

2) Confirmation test

When tested according to the quantitative method, the sample solution was confirmed to show a peak at the same retention time as the standard solution.

3) According to the herbal medicine test method of the general test method of the pharmacopeias.

4) Content test

Composition Example 2 The content of Baicalin in the granules was analyzed by high performance liquid chromatography.

5) Preservation of Specimen

Sample preservation was tested at 40 ° C. (relative humidity 75) at room temperature and in LifeTesta.

3. Experimental Results

Each experimental data was the average of the results of three or more experiments (Table 2).

Table 2

Stability test (acceleration test) according to change of composition example 2 (granule) with time

Manufacturing number Storage condition item period Room temperature Manufacturing number Storage condition item period 40 ° C., 75 R.H. Constellation Confirm Ash () baicalin content Constellation Confirm Ash () baicalin content Pilot1 Start fitness positivity 3.22 99.77 Pilot1 Start fitness positivity 3.26 99.93 2 months 3.29 99.82 2 months 3.23 99.89 4 months 3.23 99.81 4 months 3.24 99.34 6 months 3.25 98.78 6 months 3.27 98.21 Pilot2 Start fitness positivity 3.26 99.91 Pilot2 Start fitness positivity 3.23 99.91 2 months 3.23 99.90 2 months 3.24 99.88 4 months 3.26 99.82 4 months 3.25 99.76 6 months 3.24 98.33 6 months 3.22 97.49 Pilot3 Start fitness positivity 3.25 99.97 Pilot3 Start fitness positivity 3.27 99.92 2 months 3.23 99.92 2 months 3.23 99.89 4 months 3.21 99.92 4 months 3.25 99.28 6 months 3.23 98.53 6 months 3.26 97.28

Experimental Example 3

Hepatic cirrhosis-induced liver cirrhosis-induced liver extract prevention and treatment

I. Experimental Materials and Methods

Ⅰ-1. Laboratory Animals and Drugs Used

The experimental animals were supplied with 220 g-250 g (6 weeks) Sprague-Dawley male rats as ○○ boss. All experimental animals were adapted for at least one week in the ○○ university animal breeding room where constant temperature (21-25 ° C) and constant humidity (50-70) were maintained. Fasting for the experiment was 16 hours, and water and feed were freely consumed.

Silymarin was used from Sigma Chemical Co., USA and dissolved in physiological saline, and used as a manufacturing material (S) and extracting complex (S-1) and (S-2). ) Was prepared according to the Reference Examples and Examples of the present invention was dissolved in physiological saline.

Ⅰ-2 Experimental Method

Induction of cirrhosis by biliary tract ligation

Liver cirrhosis induction by biliary tract ligation was performed after 16 hours of fasting according to the method of Kountaras et al. (Br. J. Exp. Pathol. June 65 (3), 305-11, 1984). After laparotomy under ether anesthesia, the distal and proximal biliaries were ligated with sutures, cut between them, and the muscles and skin were sutured. The sham group sutured muscles and skin without ligating the biliary tract. For 4 weeks after surgery, the Sham vehicle (physiological saline) and the manufacturing single (S) were fed 12.5 mg, 6.25 mg / kg body weight, and the extract containing the extract (S-1), (S-2) and Silymarin was administered orally to each group once daily at 50 mg / 25 mg / kg body weight.

Sampling

Sampling was fasted for 16 hours on the last day of 4 weeks of administration. Body weight was measured before necropsy and blood was collected from the abdominal aorta under ether anesthesia and killed and liver was immediately removed.

A portion of the liver was taken and stored in 10 neutral formalin and some at -20 ° C. to determine the amount of hydroxyproline. Blood was left at room temperature for 1 hour, and then serum was collected by centrifugation at 3,000 rpm for 10 minutes and stored in a deep freezer (-70 ° C) for later analysis. During the experiment, the body weights of the rats were measured at the first and third day intervals to observe changes.

Sample analysis

Changes in serum biochemical markers were measured by absorbance (Milton Roy spectronic 1201, USA) using aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) kit (Sigma chemical Co., USA). Was measured.

Determination of the amount of hydroxyproline in liver tissue was determined by 6N-HC1 5 liver homogenate according to the method of Jamall et al. (Anal. Biochem., March 15: 112 (1); 70-5, 1981). After hydrolysis at 110 ℃ oxidized with chloramine-T and color development with Ehrlich's reagent solution was measured for absorbance (Milton Roy spectronic 1201, USA) at 558 nm.

Statistical processing of data

All experimental results were expressed as mean ± SEM, and data analysis was performed using Student's t- test to test the significance at p <0.05 and p <0.01.

II. Experiment result

II-1. Survival rate of experimental rats during experimental period ()

During the experimental period, the survival rate of the rats was 100 in the Sham group but was 62 in the control group and 56 in the silymarin group. Manufacturing single (S) 6.25 mg / kg experimental group was 65, 12.5 mg / kg experimental group showed a survival rate of 61. 50 mg / kg (S-1) of the extract extract containing the preparation according to the present invention was 42, 50 mg / kg (S-2) of the test group was 67, and 25 mg / kg of extract containing the preparation (S-) 1) The experimental group was 89 and the 25 mg / kg (S-2) experimental group was 78 (Table 3).

Table 3

Effects of Extracts from Complexes Containing Preparations on Survival Rate of Bile Ligation Rats

Item Test Group Dose (mg / kg) Survival rate () Sham County 100 Biliary ligation group Control 62 Silymarin 50 56 Manufacturing Single (S) 6.25 65 12.5 61 Compound Extract Extract (S-1) 25 89 50 42 Compound Extract Extract (S-2) 25 78 50 67

Initial number of animals is 8-12

vehicle (physiological saline) and drugs were orally administered for 4 weeks

II-2. Changes in Serum Biochemical Indicators

ALT and AST levels were significantly increased in all biliary ligation groups, including the control group, compared to the sham group. No ALP was significantly inhibited. In addition, ALT, AST, and ALP levels were significantly decreased in the manufacturing single (S) administration group and the combined extract extract administration group (S-1) and (S-2) compared to the control group.

In the case of manufacturing single product (S), the ALT level of the 12.5 mg / kg group was decreased by 31 compared to the control group, the AST and ALP levels were also reduced to 22. Also, the ALT level was decreased by 37 compared to the control group in the 6.25 mg / kg group. 30, ALP decreased by 20.

In particular, the 50 mg / kg administration group extract extract (S-1) containing ALT decreased 54, AST 37, ALP 24 decreased, and ALT was 55 mg / kg compared to the control group. AST decreased by 38 and ALP decreased by 30. In addition, ALP decreased by 59 compared to the control group, and AST decreased by 46 and ALP decreased by 28 in the 50 mg / kg administration group extract extract (S-2) containing the preparation, and ALT in the 25 mg / kg (S-2) administration group. Value was reduced by 54 compared to the control, AST value 52, ALP value was reduced 38 (Fig. 1, Table 4).

II-3. The amount of hydroxyproline in liver tissue

The amount of hydroxyproline was significantly increased in all biliary ligation groups, including the control group, compared to the sham group, but all drug administration groups showed a significant decrease compared to the control group. The amount of hydroxyproline in the silymarin-treated group was reduced by 32 compared to the control group, and the monosaccharide (S) 12.5 mg / kg-administered group was reduced by 28 compared to the control group. The 50 mg / kg administration group decreased 38 compared to the control group, and the 25 mg / kg administration group decreased 45 compared to the control group. In addition, in the case of the 50 mg / kg administration group extract extract (S-2) containing the preparation, the reduction was 32 compared to the control group, and decreased by 39 in the 25 mg / kg (S-2) administration group (Fig. 2, Table 4). ).

Table 4

Prevention and Effect of Hepatic Injury of Extracts Extracted from Biliary Ligation in Rats

Item Test Group Dose (mg / kg) ALT (U / L) AST (U / L) ALP (U / L) HOPro (μg / g liver) Sham County 24 ± 4 177 ± 39 157 ± 10 391 ± 45 Biliary ligation group Control 308 ± 11 ^** 665 ± 52 ^** 929 ± 31 ^** 1094 ± 56 ^** Silymarin 50 241 ± 33 ^** 592 ± 35 ^** 750 ± 39 ^{** ++} 741 ± 18 ^{** ++} Manufacturing Single (S) 6.25 194 ± 23 ^{** ++} 468 ± 44 ^{** ++} 736 ± 39 ^{** ++} 734 ± 29 ^{** ++} 12.5 212 ± 38 ^{** ++} 518 ± 32 ^{** ++} 724 ± 45 ^{** ++} 780 ± 33 ^{** ++} Compound Extract Extract (S-1) 25 137 ± 20 ^{** ++} 407 ± 58 ^{** ++} 643 ± 58 ^{** ++} 596 ± 45 ^{** ++} 50 141 ± 14 ^{** ++} 417 ± 22 ^{** ++} 702 ± 35 ^{** ++} 681 ± 32 ^{** ++} Compound Extract Extract (S-2) 25 141 ± 26 ^{** ++} 318 ± 55 ^{* ++} 576 ± 87 ^{** ++} 665 ± 45 ^{** ++} 50 126 ± 11 ^{** ++} 356 ± 65 ^{* ++} 670 ± 20 ^{** ++} 743 ± 30 ^{** ++}

The values are mean ± S.E.M. for 5 to 12 rats per group.

* = p <0.05, ** = p <0.01; significantly different from sham group.

+ = p <0.05, ++ = p <0.01; significantly different from control group.

Experimental Example 4

Comparison of Acute Toxicity of Extracts Containing Combinations in Manufacturing:

A single dose toxicity test was carried out for each of the extracts of the preparations containing the preparations obtained in Examples 1 to 6 to confirm the safety as follows.

Rat SPF (Specific Pathogen-Free) SD rats (cancer and male) were fed and administered orally to the experimental group (S-1 to S-6) according to the present invention at doses of 1.0, 2.3 and 5.0 g / kg, respectively. As a result of observation for two weeks, 70 cases of hydrated ethanol extract were not observed in all experimental animals, and no symptoms of poisoning and abnormal state were observed. In addition, two weeks after the autopsy, no peculiar findings were observed, and the half lethality (LD ₅₀ ) of each test substance is shown in Table 5 below.

Table 5

Single-dose toxicity test results of extracts from complexes containing manufacture

Experimental group Route of administration Dose (g / kg) Death Clinical symptoms Weight gain Autopsy findings Half lethality (LD _5O ) S-1 Oral administration 1.0 0/5 clear No change clear 〉 5.0 g / kg 2.3 0/5 5.0 0/5 S-2 Oral administration 1.0 0/5 clear No change clear 〉 5.0 g / kg 2.3 0/5 5.0 0/5 S-3 Oral administration 1.0 0/5 clear No change clear 〉 5.0 g / kg 2.3 0/5 5.0 0/5 S-4 Oral administration 1.0 0/5 clear No change clear 〉 5.0 g / kg 2.3 0/5 5.0 0/5 S-5 Oral administration 1.0 0/5 clear No change clear 〉 5.0 g / kg 2.3 0/5 5.0 0/5 S-6 Oral administration 1.0 0/5 clear No change clear 〉 5.0 g / kg 2.3 0/5 5.0 0/5

From the above results, it can be seen that each extract containing the extract of the preparation according to the present invention has no toxicity problem.

The pharmaceutical composition for the prevention and treatment of cirrhosis of the liver of the present invention (gumbang), gardenia, gold, and Siho in a ratio of 0.7 to 1.5: 1 to 2: 1: 1 to 2 is new in composition but has little toxicity or side effects. In addition, the drug is excellent in terms of the prevention and treatment of cirrhosis, and is very stable in terms of preparation, so that an industrially useful drug can be obtained.

Claims (6)

A pharmaceutical composition for the prevention and treatment of cirrhosis of the liver, containing Gardenia jasminoides, gold and Xu X. The pharmaceutical composition for preventing and treating liver cirrhosis according to claim 1, wherein the weight ratio of Manufacture, Gardenia jasminoides, Gold, and Shiho is contained in a weight ratio of 0.7 to 1.5: 1 to 2: 1: 1 to 2. The method according to any one of claims 1 to 3, wherein the preparation, gardenia, gold and shiho are 15 to 300 mg containing a weight ratio of 0.7 to 1.5: 1 to 2: 1: 1 to 1 once a few times. A pharmaceutical composition for preventing and treating cirrhosis of the liver. The pharmaceutical composition for preventing and treating liver cirrhosis according to claim 3, wherein the formulation of the administrable composition is a tablet, powder, granule, liquid, syrup, capsule. Prepared, Gardenia, Golden and Shiho Herbs were mixed in a weight ratio of 0.7-1.5: 1-1-2: 1: 1-2, refluxed with an organic solvent, extracted and filtered to obtain a filtrate, and the residue was added twice with an organic solvent. The filtrate obtained by extraction filtration is combined with the filtrate, concentrated under reduced pressure to prepare an extract, and then formulated into tablets, powders, granules, solutions, syrups, and capsules by containing a pharmaceutically acceptable carrier. A method for producing a liver cirrhosis preventive and therapeutic pharmaceutical composition comprising a golden ratio of 0.7 to 1.5: 1 to 2: 1: 1 to 2. The method of claim 5, wherein the organic solvent is selected from ethanol, methanol or ethyl acetate and extracted.