KR20090116923A - A pharmaceutical composition for anti-hepatitis - Google Patents

Abstract

PURPOSE: A pharmaceutical composition for treating hepatitis containing biphenyl dimethyl dicarboxylate(BDD) and Andrographis paniculata extract is provided to ensure strong protection to hepatotoxicity and effectively cure chronic hepatitis B. CONSTITUTION: A pharmaceutical composition for treating hepatitis contains biphenyl dimethyl dicarboxylate of the chemical formula 1 and Andrographis paniculata extract in the mixture ratio of 7.5-100 weight parts : 10-100 weight parts as active ingredient. The Andrographis paniculata extract contains Andrographolide of the chemical formula 2 as a main ingredient.

Description

A pharmaceutical composition for anti-hepatitis

The present invention relates to a pharmaceutical composition for treating hepatitis, and more particularly to a pharmaceutical composition useful as a therapeutic agent for chronic hepatitis B, which contains biphenyl dimethyl dicarboxylate (BDD) and cheonsimyeon extract as an active ingredient. It is about.

Chronic hepatitis B (HBV) is a disease that is widespread worldwide, especially in Asia, where the incidence of chronic hepatitis B is much higher than in other parts of the world. Chronic hepatitis B (HBV) infection can progress to cirrhosis in some patients after 5 to 20 years of infection and is highly associated with the pathogenesis of primary hepatocellular carcinoma. Although many drugs today are being used to treat chronic HBV infection, they are not satisfactory as hepatitis agents. To date, interferon-2α is the only commonly used agent for the treatment of chronic HBV and HCV infection as a monotherapy or combination therapy with ribavirin. However, the effectiveness of interferon-2α therapy is less than 30% in patients with chronic HBV and rather high side effects.

Therefore, recently, high-efficiency long-acting Peg-interferon-2α has been developed and used for the treatment of chronic HCV, but the cost is still very high for the patient. Nucleoside homologues such as lamivudine have been developed in addition to interferon, but the high rebound effect after lamivudine discontinued has limited the therapeutic effect. Moreover, lamivudine causes drug resistance by causing mutations in wild-type hepatitis B virus. In addition, several types of hepatoprotectants, such as glycidine and silymarin, have also been used to treat HBV, but these drugs have no inhibitory effect on viral replication. Therefore, new strategies are needed for the treatment of chronic HBV, and concomitant therapy is emerging as a new trend in the treatment of chronic HBV.

Biphenyl dimethyl dicarboxylate (BDD) represented by the following formula (1) is well known as a chronic hepatitis therapeutic agent (US Pat. No. 4,868,207).

The biphenyl dimethyl dicarboxylate (BDD), originally developed by scientists at the Institute of Drug Research, is a synthetic homologue of Schizandrin C isolated from the natural herb, Schisandra chinensis. Since 1979, BDD has been used as a treatment for HBV, and since 1983, it has been widely used in the treatment of chronic HBV and drug-induced hepatitis. Meanwhile, since the 1990s, it has been applied to the treatment of chronic HBV and HCV patients in Egypt, Indonesia, Vietnam and Korea. The clinical effect of BDD can be expressed as significantly lowering serum GPT without side effects. It has recently been reported that high doses of BDD can inhibit HBV replication, as indicated by the conversion of positive HBeAg and HBV-DNA to negative in patients.

The pharmacological action of BDD is: (1) hepatocellular protection against damage caused by hepatotoxic and biological toxins such as BCG plus lipopolysaccharide (LPS) through stabilization of the cell membrane, and (2) human hepatocellular carcinoma consistent with the human HBV genome. 2.2.15 inhibition of HBV replication in the cell line, (3) increased liver detoxification through the induction of liver microsomal cytochome P-450, which plays an important role in liver detoxification mechanisms, and (4) aflatoxin Antagonists of mutagenesis of chemical carcinogens such as B1.

On the other hand, cheonsimyeon contains as andrographolide (Andrographolide) represented by the following formula (2) as a main component, is known to be effective as an antiviral agent of natural products.

Andrographolide represented by the formula (2) is used as a major component of Cheonsimyeon to remove the body heat and toxins from the body. Scandinavian countries are commonly used to prevent and treat colds, and studies have shown that they can be properly administered for the purpose of anti-inflammatory, antibacterial, antiviral, cardioprotective, digestive, immunosuppressive and anticancer purposes. Most of these studies were conducted in the late 20th century and are currently being tested in cancer patients and HIV patients.

Andrographis paniculata is a herb belonging to the family of acanthaceae native to Asia, India, Malaysia, and China. In these countries, cheonsimyeon is widely used in various diseases including colds, diabetes and the like due to the beneficial effects of fresh or dried plants or their components. Andrographis paniculata is widely used as a traditional medicine for bitter tonic, antipyretic and bowel symptoms (Indian Herbal Medicine, RN Chopra, SL Nayer, IC Chopra Edit, p18, 1996; useful herbal medicine in India, SB Ambasta Edit, p 39, 1992).

The plant is also known to have antimalarial properties (Pharmacognosy, 1992, 30 (4), p263-274) and immune promoting functions (Natural Products Magazine, 1993, 56 (7), p995-999). The extract of the plant and its components are known to show good hepatoprotective function (Planta Medica, 1987, 53 (2), p135-140). Recently, several researchers have been paying attention because of cytotoxic activity, antitumor production, cell differentiation induction function and anti-HIV activity by Cheonsimyun extract.

Accordingly, the present inventors have repeatedly studied to overcome this in consideration of the fact that most of the drugs used in the conventional treatment of chronic HBV are not satisfactory, and thus the biphenyl dimethyl represented by Chemical Formula 1 used as a conventional chronic hepatitis therapeutic agent. A new pharmaceutical composition was prepared by combining Cheonsimyeon extract containing dicarboxylate (BDD) and andrographolide represented by the above formula (2) used as an antiviral agent of natural products as a main component. The present invention has been completed by confirming the significant improvement effect on hepatitis virus infection (HBV).

Accordingly, an object of the present invention is to provide a pharmaceutical composition useful as a therapeutic agent for chronic hepatitis B, containing biphenyl dimethyl dicarboxylate (BDD) and cheonsimyeon extract as an active ingredient.

In one embodiment, the present invention provides a pharmaceutical composition useful as a therapeutic agent for chronic hepatitis B, containing biphenyl dimethyl dicarboxylate (BDD) and cheonsimyeon extract as an active ingredient.

As a preferred embodiment, the present invention is a cloth core containing 7.5-200 parts by weight of biphenyl dimethyl dicarboxylate (BDD) represented by the following formula (1) and andrographolide represented by the following formula (2) as a main component Provided is a pharmaceutical composition for treating hepatitis comprising 10 to 200 parts by weight of lotus extract as an active ingredient:

[Formula 1]

[Formula 2]

Hereinafter, the present invention will be described in more detail.

The present invention is a pharmaceutical composition useful in the treatment of hepatitis, such as chronic hepatitis B virus prepared by combination therapy, biphenyl dimethyl dicarboxylate (BDD) of the formula (1) and andrographolide of the formula (2) It is characterized in that it is prepared to include the cheonsimyeon extract containing as a main ingredient as an active ingredient.

In the present invention, the mixing ratio of biphenyl dimethyl dicarboxylate (BDD) and cheonsimyeon extract represented by the formula (1) is 7.5 to 200 parts by weight: 10 to 200 parts by weight, more preferably 7.5 to 100 parts by weight It is preferable that it is 10-100 weight part. This is because if the content of biphenyl dimethyl dicarboxylate is less than 7.5 parts by weight, there is a problem of insufficient efficacy, and if it exceeds 200 parts by weight, there is a problem in safety, and if the content of cheonsimyeon extract is less than 10 parts by weight. This is because there is a problem of insufficient drug efficacy, and if it exceeds 200 parts by weight, there is a problem in safety.

In a preferred embodiment of the present invention, the andrographolide of Formula 2 in the Cheonsimyeon extract is contained in an amount of 1 to 100% by weight, preferably 3 to 50% by weight, more preferably 10 to 30% by weight. There may be.

In a preferred embodiment of the present invention, the extract of Cheonsimyeon containing the andrographolide of Formula 2 as a main component is a solvent selected from methanol, petroleum ether, chloroform, ethanol, or a mixed solvent thereof, preferably Extracted with methanol. In addition, in this invention, the said extract shall contain the extract obtained by an extraction process, the dilution or concentrate of an extract, the dried material obtained by drying an extract, or any of these modifiers or refined products.

In a preferred embodiment of the present invention, the cheonsimyeon extract can be used by further fractionation with hexane, chloroform, butanol or two or more mixed solvents of these solvents.

The pharmaceutical composition according to the present invention may contain, in addition to the above ingredients, pharmaceutically acceptable excipients such as lactose, starch, magnesium stearate, carboxymethyl cellulose, which can be easily selected by those skilled in the art.

In particular, as a preferred embodiment of the present invention, the pharmaceutical composition of the present invention contains biphenyl dimethyl dicarboxylate (BDD) represented by Formula 1 and andrographolide represented by Formula 2 as main components. It contains the same amount of agar extract and additionally includes a pharmaceutically acceptable excipient.

Cheonsimyeon extract containing biphenyl dimethyl dicarboxylate (BDD) and andrographolide as the main ingredient used as an active ingredient in the present invention as a main ingredient is already developed as a pharmaceutical and sold in foreign countries, and its stability is improved. As has been widely demonstrated, the stability of the pharmaceutical compositions according to the invention is also very high.

As described above, the pharmaceutical composition of the present invention is prepared by using cheonsimyeon extract containing biphenyl dimethyl dicarboxylate (BDD) and andrographolide as an active ingredient as an active ingredient, and using an appropriate amount of a pharmaceutically acceptable excipient. As a result, a synergistic effect of the above components shows strong protection against hepatotoxicity, which makes it very useful as a therapeutic agent for hepatitis.

Such pharmaceutical compositions according to the invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions or syrups in conventional manner.

In addition, the effective dosage of the pharmaceutical composition according to the present invention can be varied depending on the age, physical condition, weight, etc. of the patient, but is generally administered within the range of 1 to 100 mg / kg (weight) / day . And, it can be administered once a day or divided several times a day within the effective dosage range per day.

The pharmaceutical composition for treating hepatitis according to the present invention simultaneously contains biphenyl dimethyl dicarboxylate (BDD) and cheonsimyeon lotus extract as an active ingredient, thereby providing a hepatitis therapeutic agent that exhibits strong protection against hepatotoxicity by synergistic effects of the above ingredients. It has a very good effect.

Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to examples, but these examples are merely illustrative of the present invention, and the scope of the present invention is not limited only to these examples.

Example  One: Cheonsimyeon  Preparation of Extract

4 kg of dried Andrographis paniculata was finely pulverized and then extracted by heating at 60 to 80 ° C. for 1 to 5 hours in an extractor equipped with a reflux condenser with methanol solvent, and the methanol extract was filtered with a filter cloth. Extraction was performed more than once, and the extracts were combined, concentrated under reduced pressure, and the crystals obtained by leaving overnight were dried to obtain 40 g of a dry extract.

40 g of the dry extract obtained above was fractionated using nucleic acid and chloroform, and then the obtained fraction was fractionated three times with saturated butanol to obtain 24 g of butanol fraction, and finally, the present invention was prepared by recrystallization. Andrographolide content: 10% by weight).

Example  2 ~ 3: Preparation of tablet

By accurately weighing the prescribed amounts of each component shown in Tables 1 to 2 below, Cheonsimyeon extract, potato starch, talc, gelatin, hydroxypropylmethyl cellulose, silicon dioxide (anhydrous), polyethylene glycol and calcium carbonate are conventional methods. All ingredients were mixed until homogeneous, then the mixture was passed through a standard lightweight mesh screen and dried, and then the mixture was mixed with magnesium stearate and compressed in a conventional manner to prepare the tablets of Examples 2 to 3, respectively. .

Ingredient Content per Tablet (330mg) in Example 2 ingredient Content (mg) Remarks Video (BDD) 12,5 Active ingredient Cheonsimyeon extract of Example 1 (12,5 mg as andrographolide) 125.0 Active ingredient Potato starch 82.0 Excipient Talc 70.0 Excipient gelatin 12.0 Binder Magnesium stearate 5.0 A lubricant Hydroxypropyl methyl cellulose 5.5 Disintegrant Silicon dioxide (anhydrous) 2.0 Excipient Polyethylene Glycol 400 1,0 Excipient Calcium carbonate 15.0 Excipient Amount 330.0

Ingredient Content per Tablet (330mg) in Example 3 ingredient Content (mg) Remarks Video (BDD) 15.0 Active ingredient Cheonsimyeon extract of Example 1 (15 mg as andrographolide) 150.0 Active ingredient Potato starch 67.0 Excipient Talc 58.0 Excipient gelatin 12.0 Binder Magnesium stearate 5.0 A lubricant Hydroxypropyl methyl cellulose 5.0 Disintegrant Silicon dioxide (anhydrous) 2.0 Excipient Polyethylene Glycol 400 1,0 Excipient Calcium carbonate 15.0 Excipient Amount 330.0

Example  4-5: Production of hard capsule

Accurately weigh the prescribed amounts of each ingredient listed in Tables 3 to 4 below, first mix Cheonsimyeonx, lactose, starch and carboxymethylcellulose until all components are homogeneous in a conventional manner and then mix the mixture to standard lightweight After drying by passing through a mesh screen, the mixture was mixed with magnesium stearate and filled into hard capsules in a conventional manner to prepare hard capsules of Examples 4 to 5, respectively.

Ingredient Content per 1 Capsule (300 mg) of Example 4 ingredient Content (mg) Remarks Video ( B DD) 12.5 mg Active ingredient Cheonsimyeon extract of Example 1 (12,5 mg as andrographolide) 125 mg Active ingredient Lactose 90 mg Excipient Starch 64 mg Excipient Magnesium stearate 5.0 mg Excipient Carboxymethyl Cellulose 3.5 mg Excipient Amount 300 mg

Component Content per 1 Capsule (300 mg) of Example 5 ingredient Content (mg) Remarks Video (BDD) 15.0 mg Active ingredient Cheonsimyeon extract of Example 1 (15 mg as andrographolide) 150 mg Active ingredient Lactose 67 mg Excipient Starch 60 mg Excipient Magnesium stearate 5.0 mg Excipient Carboxymethyl Cellulose 3.0 mg Excipient Amount 300 mg

Experimental Example  1: investigation of antiviral effects

Total RNA was extracted using Trizol Reagent (Life Technologies, USA) from each group of 1 × 10 ⁷ / ml liver cancer cell lines (HepG2, Korea Cell Line Bank). That is, 1 ml of Trizol reagent was added to lyse the cells and allowed to stand at room temperature for 5 minutes, followed by centrifugation at 13500 rpm for 15 minutes by adding 200 μL of chloroform. The clear supernatant was taken, transferred to a new tube, the same amount of isopropyl alcohol was added, and RNA was precipitated by centrifugation at 13500 rpm for 10 minutes. RNA pellet was washed with 1 mL of 75% EtOH diluted with DEPC-treated distilled water, dried in air and used as a reverse transcription sample. The primers used for the PCR reaction on the cDNA template were 6-16 (sense: CAA GCT TAA CCG TTT ACT CGC TGC TGT, antisense: TGC GGC CGC TGC TGG CTA CTC CTC ACC T) and the target size was 533bp. The reaction volume was 20 μl and electrophoresed on 1.2% agarose gel stained with ethidium bromide and observed on UVDoc (UVItec, UK).

HepG2 is one of liver cancer cell models frequently used in studies related to liver cancer and hepatocytes, and therefore, in the present invention, it was intended to study the reactivity of hepatocytes after HBV infection. This cell line culture was used after passing and seeding for about 1 week in primary culture in 10% FBS-RPMI medium.

Experimental results were as shown in FIG. Cont is control, IFN is treated with interferon-γ (1000IU), CS is treated with Cheonsimyeon extract (150 ㎍ / mL) alone, BDD is treated with BDD (300 μg / mL) alone, and C / B is Cheonsimyeon Extract (150 μg / mL) and video (150 μg / mL) were mixed.

When external virus affects hepatocytes, infected hepatocytes (in the present invention using hepG2 hepatocytes) secrete interferon to induce interferon and antiviral proteins to neighboring hepatocytes. Therefore, in the present invention, 6-16 genes expressed by interferon were observed. As shown in FIG. 1, 6-16 gene was expressed during CS alone treatment and co-treatment with BDD.

Experimental Example  2: Anti - HBV  Effect investigation

Total RNA was extracted from each group of 1 × 10 ⁷ / ml HBV-infected liver cancer cell lines (Hep3B, Korea Cell Line Bank) using Trizol Reagent (Life Technologies, USA). That is, 1 ml of Trizol reagent was added to lyse the cells and allowed to stand at room temperature for 5 minutes, followed by centrifugation at 13500 rpm for 15 minutes by adding 200 μL of chloroform. The clear supernatant was taken, transferred to a new tube, the same amount of isopropyl alcohol was added, and RNA was precipitated by centrifugation at 13500 rpm for 10 minutes. RNA pellet was washed with 1 mL of 75% EtOH diluted with DEPC-treated distilled water, dried in air and used as a reverse transcription sample. Primers used for PCR reactions on cDNA templates include HBsAg (sense: gaa gca ccc aag tgt cct gg, antisense: aaa cgg act gag gcc cac tc), pgRNA (sense: GGC CCA CTC ACA GTT AAT GAG A, antisense : ACA GGT GCA ATT TCC GTC CG), GAPDH (sense: CCA TCA CCA TCT TCC AGG AG, antisense: CCT GCT TCA CCA CCT TCT TG) and 380bp and 1.2kb 576bp, respectively. The reaction volume was 20 μl and electrophoresed on 1.2% agarose gel stained with ethidium bromide and observed on UVDoc (UVItec, UK).

Hep3B is a cell line having a characteristic of secreting HBV surface antigen and is one of cell models used for HBV drug screening. This cell line culture was used by passing and seeding after primary culture for about 1 week in 10% FBS-RPMI medium.

The experimental results were as shown in FIG. Cont is control, IFN is treated with interferon-γ (1000IU), CS is treated with Cheonsimyeon extract (150 ㎍ / mL) alone, BDD is treated with BDD (300 μg / mL) alone, and C / B is Cheonsimyeon Extract (150 μg / mL) and video (150 μg / mL) were mixed.

Hep3B (HBsAg secretion), an HBV infected cell line, was used to determine whether to block gene transcription for antigen production. As shown in the results of FIG. 2, HBsAg was found to inhibit the expression of the HBsAg gene upon interferon treatment. These results showed similar results in the BDD group. Also, C / B group was thought to have better inhibitory effect than CS alone treatment. In the case of pgDNA, in contrast to HBsAg, when combined with CS alone and BDD, it was thought to have a superior transcription inhibitory effect than interferon.

Experimental Example  3: investigation of anti-inflammatory effect

Total RNA was extracted from each group of 1 × 10 ⁷ / ml macrophage lines (RAW264.7, ATCC) using Trizol Reagent (Life Technologies, USA). That is, 1 ml of Trizol reagent was added to lyse the cells and allowed to stand at room temperature for 5 minutes, followed by centrifugation at 13500 rpm for 15 minutes by adding 200 μL of chloroform. The clear supernatant was taken, transferred to a new tube, the same amount of isopropyl alcohol was added, and RNA was precipitated by centrifugation at 13500 rpm for 10 minutes. RNA pellet was washed with 1 mL of 75% EtOH diluted with DEPC-treated distilled water, dried in air and used as a reverse transcription sample. Primers used for PCR reactions on cDNA templates were IL-1β (sense: agc tgt ggc agc tac ctg tg, antisense: gct ctg ctt gtg agg tgc tg), β-actin (sense: tga ccg agc gtg gct aca gc :, antisense: acc gct cat tgc cga tag tg) and 522bp and 186bp, respectively, as target sizes. The reaction volume was 20 μl and electrophoresed on 1.2% agarose gel stained with ethidium bromide and observed on UVDoc (UVItec, UK).

The RAW264.7 cells are various cell lines used for the characterization of anti-inflammatory and macrophages. In the present invention, experiments for inhibiting inflammatory factors among macrophages are performed. This cell line culture was used by passing and seeding after about 3 days of primary culture in 5% FBS-DMEM medium.

Experimental results were as shown in FIG. Cont is control, IFN is treated with interferon-γ (1000IU), CS is treated with Cheonsimyeon extract (150 ㎍ / mL) alone, BDD is treated with BDD (300 μg / mL) alone, and C / B is Cheonsimyeon Extract (150 μg / mL) and video (150 μg / mL) were mixed.

In this experimental example, we observed whether the expression of inflammatory cytokines (IL-1β) of each treatment drug was inhibited by LPS, an inflammatory stimulant, using RAW264.7 cells, which are mouse macrophage lines. As shown in the results of FIG. 3, the anti-inflammatory effect was expected because the expression of IL-1β was inhibited when CS, BDD alone and C / B were combined.

According to the experimental results of Experimental Examples 1 to 3, the pharmaceutical composition containing Cheonsimyeon extract and BDD of the present invention had anti-viral (IFN-like effect) effect, as well as HBV's replication inhibition, anti-inflammatory effect and immunoreactivity effect. Is expected to contribute significantly to the treatment and prevention of chronic hepatitis B infection. In addition, as shown in the results of Experimental Example 1 to Experimental Example 3 can be predicted the antiviral effect and anti-inflammatory effect in the concentration of about two times less than the BDD in the case of Cheonsimyeon extract.

Experimental Example  4: Toxicity test Cytotoxicity test )

MTT assay is a method for measuring cell viability by the amount of formazan formed by mitochondrial dehydrogenase of living cells. In the present invention, total cytotoxicity test was performed by extracting total splenocytes from spleen with various immune cells. That is, 10 μg / mL of MTT (5 mg / ml in PBS) was added to a 96 well plate containing cells treated with appropriate drug in each group, and cultured at 37 ° C. for 4 hours. It was dissolved in 10% SDS (in 0.01 N HCl) and the absorbance was measured at 570 nm and used for the analysis of the present invention.

The experimental results were as shown in FIG.

In this experiment, splenocytes containing mouse lymphocytes were extracted and subjected to cytotoxicity test of each drug. As shown in the results, the safety range of BDD is considered to be very wide. In the case of Cheonsimyeon extract, cytotoxicity is observed when it exceeds 500 μg / mL, and the effect can be predicted even at very low concentrations. As a result, more effective drug efficacy could be predicted.

As described above through the above examples, the pharmaceutical composition for treating hepatitis of the present invention simultaneously contains biphenyl dimethyl dicarboxylate (BDD) and cheonsimyeon extract as an active ingredient, thereby improving the hepatotoxicity by synergistic effects of the components. It is a very useful invention in the pharmaceutical industry because it has a very excellent effect to provide a therapeutic agent for hepatitis showing a strong protection against.

Figure 1 shows the results of examining the antiviral effect of each composition. Cont is control, IFN is treated with interferon-γ (1000IU), CS is treated with Cheonsimyeon extract (150 ㎍ / mL) alone, BDD is treated with BDD (300 μg / mL) alone, and C / B is Cheonsimyeon Extract (150 μg / mL) and video (150 μg / mL) were mixed.

Figure 2 shows the results of examining the anti-HBV effect of each composition. Cont is control, IFN is treated with interferon-γ (1000IU), CS is treated with Cheonsimyeon extract (150 ㎍ / mL) alone, BDD is treated with BDD (300 μg / mL) alone, and C / B is Cheonsimyeon Extract (150 μg / mL) and video (150 μg / mL) were mixed.

Figure 3 shows the results of examining the anti-inflammatory effect of each composition. Cont is control, IFN is treated with interferon-γ (1000IU), CS is treated with Cheonsimyeon extract (150 ㎍ / mL) alone, BDD is treated with BDD (300 μg / mL) alone, and C / B is Cheonsimyeon Extract (150 μg / mL) and video (150 μg / mL) were mixed.

Figure 4 shows the toxicity test results in the treatment of Cheonsimyeon extract alone, BDD alone, and mixed treatment.

Claims (7)

A pharmaceutical composition for treating hepatitis comprising biphenyl dimethyl dicarboxylate represented by the following Chemical Formula 1 and cheonsimyeon extract as an active ingredient: [Formula 1]

The pharmaceutical composition for treating hepatitis of claim 1, wherein the mixing ratio of biphenyl dimethyl dicarboxylate and cheonsimyeon extract is 7.5-100 parts by weight: 10-100 parts by weight. [Claim 2] The pharmaceutical composition for treating hepatitis of claim 1, wherein the cheonsimyeon extract contains andrographolide represented by the following Chemical Formula 2 as a main component: [Formula 2]

4. The pharmaceutical composition for treating hepatitis of claim 3, wherein the content of andrographolide in the extract of Cheonsimyeon is 1 to 100% by weight. The pharmaceutical composition for treating hepatitis of claim 1, wherein the cheonsimyeon extract is extracted with a solvent selected from methanol, petroleum ether, chloroform, ethanol, or a mixed solvent thereof. The pharmaceutical composition for treating hepatitis of claim 5, wherein the cheonsimyeon extract is further fractionated with hexane, chloroform, butanol, or two or more mixed solvents of these solvents. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a formulation of powder, granule, tablet, capsule, suspension, emulsion, or syrup.

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