KR20090109020A - Pharmaceutical composition for treating liver injury induced by the treatment of hyperlipidemia comprising the extract from Eugenia caryophyllata - Google Patents

Abstract

PURPOSE: A pharmaceutical composition for treating liver injury caused by treatment of hyperlipidemia, which contains Syzygium aromaticum extract is provided to prevent liver damage by administering drug for hyperlipidemia. CONSTITUTION: A pharmaceutical composition for treating liver injury caused by treatment of hyperlipidemia contains Syzygium aromaticum extract as an active ingredient. The composition contains cinnamon, Myristica fragrans Houtt, Atractylodis Rhizoma, magnolia obovata, and Corydalis turtschaninovii. The composition further comprises Lindera Root and Glycyrrhiza uralensis extract. The extract is isolated through freeze-drying or spray drying.

Description

Pharmaceutical composition for treating liver injury induced by the treatment of hyperlipidemia comprising the extract from Eugenia caryophyllata}

The present invention relates to a pharmaceutical composition for the prevention and treatment of liver damage caused by the intake of a high fat diet containing clove extract as an active ingredient, and also to a liver protector for treating the liver and protecting the liver damaged by the administration of hyperlipidemic drugs. It is about.

Cholesterol is obtained through animal food or synthesized in vivo. On the other hand, if cholesterol is present in the body more than necessary, it is known to cause various adult diseases such as cardiovascular disease caused by hyperlipidemia. For example, hyperlipidemia can occur, which is a high risk of developing atherosclerotic diseases (angina, myocardial infarction, cerebral infarction, peripheral vascular disease, etc.) due to high blood lipids.

In particular, a high cholesterol diet increases blood cholesterol levels. If such a large amount of cholesterol is present in the blood, the liver is damaged by oxidative stress, causing inflammation and inducing liver fibrosis (Bayard M, Holt J and Boroughs E. Nonalcoholic fatty liver disease.American Academy of Family Physicians 2006. 73: 1961-1968).

Recently, hyperlipidemia, fat peroxidation, and stellate cell activation in the liver of mice fed a high fat diet have been shown to induce fatty liver disease in the preliminary stages of cirrhosis, and fatty acid synthesis, oxidative stress, inflammation, and fibrosis by high fat diet. Induction of hepatic expression of genes involved in, and in contrast, high-fat diets have been reported to reduce the expression of antioxidant enzymes resulting in increased oxidative stress (Matsuzawa, M and Takamura, T et al., Lipid-induced). oxidative stress causes steatohepatitis in mice fed an atherogenic diet.Hepatology 2007: 46: 1392-1403).

In addition, as a result of long-term high-fat diet in mice, it was confirmed that MCP-1 mRNA was expressed at the stage before induction of TNF alpha and type 1 collagen mRNA which induces liver fibrosis, and MCP-1 mRNA expression was the same as that of high-fat diet. It has been reported that non-alcoholic steatohepatitis is closely related to obesity in humans by establishing a mechanism by which MCP-1 is involved in obesity and progresses liver fibrosis (Ito, M and Suzuki, J et al., Longitudinal analysis). of murine steatohepatitis model induced by chronic exposure to high-fat diet.Hepatol Res. 2007 37: 50-57).

On the other hand, hyperlipidemia, a rapidly increasing trend, refers to a condition in which cholesterol or triglyceride concentrations are increased in blood, and is not a disease state showing clinical findings by itself, but it is an agent that causes atherosclerosis, further myocardial infarction and cerebral infarction. It is a risk factor of 1. A large epidemiological study (US Framingham Study) found that hyperlipidemia, especially hypercholesterolemia, correlated very positively with the incidence of ischemic heart disease. These correlations vary with age, and the increase in serum cholesterol levels before age 40 is more closely associated with the incidence of ischemic heart disease than after age 40. According to Korean Patent Publication No. 2005-69410, a total of 40,000 people who have been followed for 4 years, if they reduce cholesterol levels by 10%, the mortality rate due to heart disease decreases by more than 20%. It has been reported that there is an effect of reducing the incidence of myocardial infarction by 17%.

The treatment of hypercholesterolemia is the most efficient way to prevent and treat coronary heart disease. Currently, the antihyperlipidemic drugs are widely used as statin compounds (eg, pravastatin, simvastatin, lovastatin, atorvastatin, fluvastatin, ceriva) which are cholesterol inhibitors. Statins, itavastatin and the like), fibrate-based compounds (eg, bezafibrate, clofibrate, simfibrate, clinofibrate, etc.) having a squalene synthetase inhibitory or triglyceride-lowering effect.

However, statin-based hyperlipidemia drugs, which are widely used as hyperlipidemia drugs, cause liver damage, and one of the most decisive side effects of statin-based drugs has been reported to be hepatotoxicity (Talbert RL., 'Safety issues with statin therapy', J Am Pharm Assoc (2003) .2006 Jul-Aug; 46 (4): 479-88; quiz 488-90), simvastatin activates liver transaminase enzymes (Dennis Cordato, David Sharpe and Phillip Barnes, 'Valproate hepatotoxicity in an adult patient taking Simvastatin ', Journal of Clinical Neuroscience, Volume 4, Issue 4, October 1997, Pages 500-502), and it has been reported that serious hepatotoxic risks should be considered when rosuvastatin is administered in the general clinical range ( Famularo G, Miele L, Minisola G, Grieco A., 'Liver toxicity of rosuvastatin therapy', World J Gastroenterol. 2007 Feb 28; 13 (8): 1286-8).

Fibrate-based hyperlipidemia drugs also cause liver damage and are known to cause hepatotoxicity, including hepatomegaly and liver cancer (Paul D. Cornwell, Angus T. De Souza and Roger G. Ulrich, 'Profiling of hepatic gene expression in rats treated with fibric acid analogs', Mutation Research / Fundamental and Molecular Mechanisms of Mutagenesis, Volume 549, Issues 1-2, 18 May 2004, Pages 131-145), and reported that clofibrate activates the amino transferase enzyme. JA Kramer, EA Blomme, RT Bunch, JC Davila, CJJackson, PF Jones, KL Kolaja, SW Curtiss, 'Transcription profiling distinguishes dose-dependent effects in the livers of rats treated with clofibrate', Toxicol. Pathol. 31 ( 2003) 417-431).

Therefore, there is an urgent need for the development of drugs that can treat or cause liver damage caused by drugs in the treatment of high fat diet or hyperlipidemia.

Many literatures are known to be effective in treating hyperlipidemia. For example, the Republic of Korea Patent Publication No. 207958 is known that the leaf leaves are effective in cardiovascular diseases caused by hypercholesterolemia, and in Korea Patent Publication No. 2000-21073, Hyunho colors have the effect of inhibiting cholesterol biosynthesis. Korean Patent Laid-Open Publication No. 2003-70059 discloses multiple risk factor syndromes such as visceral fat type obesity, diabetes, hyperlipidemia and hypertension selected from the group consisting of licorice hydrophobic extract, turmeric extract, clove extract and cinnamon extract. Compositions for prevention or improvement are known, and Korean Patent Laid-Open No. 2006-26408 discloses that red pepper has an effect of lowering lipids in the body selected from serum cholesterol or liver fat.

In addition, the Republic of Korea Patent Publication No. 1998-39743 is known to have a cholesterol-lowering effect of eugenol, an extract component of the clove, and the Republic of Korea Patent Publication No. 2003-93712 is effective to create, white leaf, golden, bokyeong and licorice It is known that the herbal composition consisting of ingredients does not lower the concentration of cholesterol in the serum elevated by the high cholesterol diet, but can suppress the occurrence of atherosclerosis.

On the other hand, herbal medicines that are effective in liver disease are also known in many literatures. Republic of Korea Patent Publication No. 626724 discloses aspartate aminotransfer containing mixed extracts including Injin, Creation, Hubak, Dermis, Heraldic, Taxa, Baekchul, Bokryeong, Nabokjaja, Ginger, Banja, Daebokpi, Samreung, Sesame, Cheongpi and Licorice It has been known to inhibit liver fibrosis by having an effect of inhibiting enzyme activity such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and herbal preparations are known to have aspartate aminotransferase in blood. aminotransferase (AST) and alanine aminotransferase (ALT) activity has been reported to have an inhibitory effect (3rd Proceedings of the Korean Acupuncture Society, Vol. 7, 2. 2004), Korean Patent Application Publication 2003-33282 describes cinnamon extracts for their hepatoprotective, atherosclerosis, antioxidant and anti-aging effects.

The present invention finds a medicinal use capable of treating liver damage caused by administration of a drug for treating high fat diet or hyperlipidemia, which has not been conventionally known in the extract, and completed the present invention.

An object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of liver damage caused by high fat diet.

In addition, it is an object of the present invention to provide a hepatoprotective agent that can protect the liver damaged by hyperlipidemia drug treatment simultaneously with the treatment of hyperlipidemia.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of liver damage caused by a high fat diet containing clove extract as an active ingredient.

The clove extract may be dried and ground to crush the clove, and then cooled in a 10-fold extraction solvent for one day, and then the extraction stock solution may be obtained by filtration, concentration, and lyophilization, and the extraction solvent may be selected. It does not specifically limit in. Extraction solvents include lower alcohols such as purified water, ethanol, methanol, isopropyl alcohol, n-butanol, polyhydric alcohols such as glycerol, propylene glycol, 1,3-butylene glycol, ethyl acetate, methyl acetate, benzene, n- Hydrocarbon solvents, such as hexane, diethyl ether, and dichloromethane, are mentioned, for example, One or two or more types of these solvents can be mixed and used for extraction.

The extract can be extracted by using a liquid extract, pill, tablets, capsules, suspensions, syrups and the like to extract the extract using a liquid extract, soft extract, freeze-dried and spray drying method.

The present invention may further include herbal medicines that can be mixed with the clove extract as well as the clove extract. For example, the cutlet bow master queue ^® available on the market by the present applicant is a composition of a mixed herbal extract of clove, health, cinnamon, nutmeg, catechu, dermis, generating, magnolia, Corydalis and pepper as the active ingredient (the "cutlet Hwa Myung Su Q ^® composition), and Hwa Myung Soo ^® Gold is a blended herbal extract of clove, health, cinnamon, nutmeg, sun medicinal herbs, dermis, creation, peppermint, calendula, red pepper, ointment, fruit and licorice. Composition (hereinafter 'Bow Myung Soo ^® Gold Composition ", or as a bowels bow water Suq ^® composition or bow water ^® gold The composition contains clove extract and is included in the scope of the clove extract containing composition of the present invention.

As described in the following experimental examples, in the present invention, not only cloves extracts but also casquem Sucu ^® composition or life sui ^® gold The composition was able to cure liver damage caused by a high fat diet through changes in liver weight, inhibitory activity of blood aspartate aminotransferase and alanine transferase enzyme and changes in tissue liver lesion sites.

In addition, the present invention provides a hepatoprotective agent that can protect the liver damaged by hyperlipidemia drug treatment simultaneously with the treatment of hyperlipidemia containing clove extract as an active ingredient.

The pharmaceutical composition that can protect the liver damaged by hyperlipidemic drug treatment simultaneously with the treatment of hyperlipidemia may further include herbal medicines known for treating hyperlipidemia that can be mixed with cloves as well as cloves extracts according to the present invention.

To as described in Experiment Example, clove extract, as well as bow cutlet master in animal models induced hyperlipidemia queue ^® composition or bow master ^® Gold The composition was found to have the effect of inhibiting total cholesterol, triglycerides, LDL cholesterol production and increasing HDL cholesterol production.

The present invention can be administered in a variety of oral and parenteral formulations in actual clinical administration, the most preferred route of administration is oral administration. In addition, when formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants that are generally used are prepared.

Solid preparations for oral administration may include tablets, pills, powders, granules, capsules, and the like, which may include one or more excipients, for example microcrystalline cellulose, low-substituted hydroxypropyl cellulose, colloidal oxidation Silicon, calcium silicate, starch, calcium carbonate, sucrose or lactose, gelatin and the like can be mixed, and in addition to simple excipients, lubricants such as magnesium styrate talc can also be used. In addition, liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups, and various excipients, for example, wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents, water and liquid paraffin. Etc. may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In addition, the dosage or dosage of the clove extract according to the present invention varies depending on the weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of the patient, and the adult standard It is preferable to take a dose of 1 mg / kg to 1000 mg / kg divided once to several times.

The present invention can treat liver damage caused by a high fat diet by administering a clove extract, and thus can be usefully used as a pharmaceutical composition for preventing and treating liver damage caused by a high fat diet containing a clove extract as an active ingredient. Can be.

In addition, the present invention can protect the liver damaged by the administration of hyperlipidemia at the same time as the treatment of hyperlipidemia, can be developed as a liver protector to protect the liver damaged by the administration of hyperlipidemia at the same time as the treatment of hyperlipidemia containing clove extract as an active ingredient have.

Hereinafter, the present invention will be described in more detail. However, these Examples are only illustrative of the present invention, and the scope of the present invention is not limited to these.

<Example 1> Preparation of herbal extracts according to the present invention (1)

1 g of 95% ethanol was added to 100 g of cloves, followed by immersion for 1 day.

<Example 2> Preparation of herbal extracts according to the present invention (2)

3L of 70% alcohol is added to the herbal mixture (Casvum Soomyung Suq ^® composition), which contains 12 g of clove, 12 g of health, 30 g of cinnamon, 6 g of nutmeg, 100 g of dermis, 250 g of dermis, 3 g of dried fruit, 50 g of haricot, 180 g of calendula, and 6 g of red pepper. After dipping for 1 day, the leachate was distilled out and concentrated under reduced pressure to prepare a concentrate of 649 mg.

<Example 3> Preparation of herbal extracts according to the present invention (3)

Cloves 12g, Health 12g, cinnamon 30g, nutmeg 6g, catechu 100g, dermal 150g, creating 3g, Magnolia 50g, Corydalis 180g, pepper 6g, ohyak 150g, jisil 100g and licorice 50g a herbal mixture mixing (bow master ^® Gold Composition) 3L of 70% alcohol was added thereto to immerse for 1 day, and then the leachate was distilled off and concentrated under reduced pressure to prepare a concentrate of 849 mg.

< Reference Experiment  1> High fat In the diet  by Liver damage  Trigger confirmation test

1) Changes in liver weight due to high fat diet

To identify liver damage caused by high-fat diet, the high-fat diet group was selected from ICR mice and fed a high-fat diet (40% beef tallow AIN-76A rodent diet, Dyets Inc., PA, USA) for 84 days (1). ), And the change in liver weight was observed, and the results are shown in Table 1.

TABLE 1

In general, when excess fat is absorbed by the supply of a high fat diet, the liver accumulates and causes significant fat change, thereby increasing the weight of the liver. As can be seen in Table 1, in the high-fat diet group (1) it can be confirmed that excess fat is accumulated in the liver compared to the normal group, the liver weight is greatly increased, causing liver damage.

2) Changes in AST and ALT Contents due to High Fat Diet

High fat diet group fed with high fat diet group (1) and 45% kcal high fat pellet feed (D12451; Diet Research, PA, USA) for 84 days to identify liver damage caused by high fat diet. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) content changes in blood of (2) were observed in Tables 2-1 and 2-2.

AST activity was measured in 100 ml of serum in Hepes buffer (pH 7.4) containing 1 ml of L-asparaginate 200 mM, 2-oxoglutarate 12 mM, malate dehydrogenase 600 Unit / L and NADH 0.25 mM. Was added to determine the hourly decrease in absorbance at 340 nm (S. Retman et al., Arm. J. Clin. Patrol. (28), 58-63, 1957), and the activity of ALT was 1 ml of L-. 100 μl of serum was added to Hepes buffer (pH 7.4) containing 400 mM alanine, 12 mM 2-oxoglutarate, 2,000 Unit / L acetate dihydrogenase, and 0.25 mM NADH to obtain an hourly decrease in absorbance at 340 nm. Measurements were made using an automated blood analyzer (AU400, Olympus, JAPAN) (S. Retman et al., Arm. J. Clin. Patrol. (28), 58-63, 1957).

TABLE 2-1

Table 2-2

As can be seen from Table 2-1 and Table 2-2, in the high fat diet group (1) and the high fat diet group (2), the amount of AST and ALT in the blood increased significantly compared to the normal group, respectively, to the extent that liver disease is induced. It can be confirmed that it caused liver damage.

3) Liver histological changes according to high fat diet

In order to confirm the liver damage caused by the intake of a high fat diet, the high fat diet group (1) and the high fat diet group (2) were bleeded, and the livers were extracted and weighed, and the extracted livers were 10% neutral buffered. Fixed with formalin solution. Subsequently, the tissues were embedded in paraffin through a general tissue treatment process, sections of 3-4um were made, and then stained with Hematoxylin & Eosin (H & E) to observe histopathological changes of the liver (proportion of fatty liver lesion area and hepatocellular diameter) by optical microscope. Table 3-1 and Table 3-2.

Table 3-1

Table 3-2

Liver fat change is a typical steatosis caused by high-fat diets and is generally observed in high-fat diet animals. As can be seen from Table 3-1 and Table 3-2, in the high fat diet group (1) and the high fat diet group (2), the area of fat degeneration was significantly increased compared to the normal group by the high fat diet intake, and the hepatocyte size It can also be seen that significantly increased liver damage.

< Reference Experiment  2> High fat In the diet  Hyperlipidemia-induced confirmation test

1) Changes in Total Cholesterol and Neutral Lipid by High Fat Diet

High fat diet group (1) of ICR mice induced hyperlipidemia with high fat diet (40% beef tallow AIN-76A rodent diet, Dyets Inc., PA, USA) for evaluation of total cholesterol and triglyceride changes according to high fat diet Serum total cholesterol and triglycerides were measured using the hyperlipidemic model of the high-fat diet group (2) induced by ingestion of 45% kcal high-fat pellet feed (D12451; Diet research, PA, USA). Shown in

Table 4-1

Table 4-2

As can be seen from Table 4-1 and Table 4-2, in the high fat diet group (1) and the high fat diet group (2), hypercholesterolemia was significantly increased due to the increase in total blood cholesterol and triglycerides in blood compared to the normal group by the intake of high fat diet. It can be seen that caused.

2) Changes in LDL and HDL Levels in Blood According to High Fat Diet

The low-fat lipoprotein (LDL) and high-density lipoprotein (HDL) contents of the high-fat diet group (1) and the high-fat diet group (2) were measured and the results are shown in Table 5-1 and It is shown in Table 5-2.

Table 5-1

Table 5-2

As can be seen from Table 5-1 and Table 5-2, high-fat diet group (1) and high-fat diet group (2) caused hyperlipidemia by significantly increasing blood LDL compared to normal group by high-fat diet intake. In addition, it can be seen that significantly reducing blood HDL causes circulatory diseases including hyperlipidemia.

< Experimental Example  1> Of the present invention extract Liver weight  Assessment of hepatoprotection following inhibition of change

In order to confirm the hepatoprotective effect by the administration of the clove extract, the degree of liver weight change was evaluated using a hyperlipidemia model of ICR mice. The experimental method was selected by measuring ICR mice and feeding the high-fat diet (40% beef tallow AIN-76A rodent diet, Dyets Inc., PA, USA) and measuring the body weight every week for 84 days after one week of feeding the high-fat diet. According to one weight, the extract obtained in Examples 1 and 3 of the present invention (Blumyeongsoo ^® Gold Composition) was diluted daily to 20 mg / ml (5% ethanol) in the amount of clove raw medicine for 10 ml / kg In Example 3, in the case of Example 3, the total crude drug was diluted to 113.2mg / 10ml, orally administered once daily at 10ml / kg, and sacrificed to observe changes in liver weight.

In the comparison group, high-fat diet (40% beef tallow AIN-76A rodent diet, Dyets Inc., PA, USA) was measured at the same time and weighed at weekly intervals for 84 days from 1 week after feeding high-fat diet. Daily HMG Co A reductase inhibitor simvastatin 10mg / kg orally administered with a high-fat diet at a concentration of 10ml / kg, and the high-fat diet group (1) administered only a high-fat diet as a control group in Examples 1 and 3 liver The change in amount is compared and the results are shown in Table 6.

TABLE 6

As can be seen in Table 6, Examples 1 and 3 according to the present invention is superior to the high-fat diet group (1) that caused liver damage by inhibiting the increase in liver weight, even when administered together with a high-fat diet was excellent Able to know. On the other hand, despite the simvastatin HMG Co A reductase inhibitors in the comparison group it can be seen that the liver weight is increased by the administration of simvastatin to increase the weight of the liver than the high fat diet group (1).

Experimental Example 2 Evaluation of liver protection according to the inhibition of changes in AST and ALT content according to the present invention

1) Experimental animals to which the composition of Example 1 and Example 3 (Bilming water ^® gold composition) were administered in the same manner as Experimental Example 1 to confirm the hepatoprotective effect according to the present invention, blood aspartate aminotransfer of the comparison group Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) content changes were measured and the results are shown in Table 7.

TABLE 7

As can be seen in Table 7, Examples 1 and 3 according to the present invention, compared to the high fat diet group (1) that caused liver damage, significantly ingested a high fat diet even when the high fat diet was administered together by suppressing the blood AST and ALT concentrations. It can be seen that the liver protective effect that can be caused by the excellent. On the other hand, the comparison group, even though simvastatin is HMG Co A reductase inhibitors, it can be seen that the blood AST and ALT concentration is increased than the high-fat diet group (1) to cause liver damage by simvastatin administration.

2) In order to confirm the liver protection effect according to the present invention 1) the hyperlipidemic model of the mouse induced by the experiment and other high fat feed 45% kcal high fat pellet feed (D12451; Diet research, PA, USA) intake was used.

Experimental method is based on the weight measured by measuring the body weight at a weekly interval for 84 days from one week after high-fat feed fed to the total raw drug amount 173.07mg / 20ml obtained in Example 2 (Cathus bow Myung Sukyu ^® composition) of the present invention every day Diluted and orally administered once at 20ml / kg and observed changes in blood AST and ALT concentrations.

In the same manner as the method described above, the HMG Co A was measured daily by weighing the body weight at a weekly interval for 84 days from the first week after the high fat feed and at the same time as the high fat pellet feed (D12451; Diet research, PA, USA). 10 mg / kg of the reductase inhibitor simvastatin was orally administered with a high fat diet at a concentration of 10 ml / kg, and the blood AST and ALT concentrations of Example 2 were compared with the high fat diet group (2) receiving only the high fat diet as a control. The results are shown in Table 8.

TABLE 8

As can be seen from Table 8, Example 2 according to the present invention by the intake of high-fat diet, even though the high-fat diet was administered by suppressing the blood AST and ALT concentration significantly compared to the high-fat diet group (2) that caused liver damage. It can be seen that the liver protection effect that can be induced is very good. On the other hand, it can be seen that the comparison group causes liver damage by simvastatin administration as in 1) above.

Experimental Example 3 Liver histopathological changes according to administration of the extract of the present invention

1) In order to confirm the protective effect of the liver according to the present invention, the experiment was conducted in the same manner as in Experimental Example 1, and then the animals were bled to death and the livers were collected and weighed, and then the livers were removed with 10% neutral buffered formalin solution. Fixed. Subsequently, the tissues were embedded in paraffin through a general tissue treatment process, sections of 3-4um were made, and then stained with Hematoxylin & Eosin (H & E) to observe histopathological changes of the liver (proportion of fatty liver lesion area and hepatocellular diameter) by optical microscope. It is shown in Table 9.

TABLE 9

As can be seen in Table 9, Examples 1 and 3 according to the present invention, compared to the high-fat diet group (1) that caused liver damage, significantly inhibited the increase of fat degeneration and hepatocytes, but the high-fat diet was administered together. It can be seen that the liver protection effect that can be caused by ingestion is very good. On the other hand, the comparison group is similar to the high fat diet group (1), it can be seen that the liver damage caused by simvastatin administration.

2) In order to reconfirm the effect of protecting the liver according to the present invention, experiments were performed in the same manner as 2) of Experimental Example 2 to observe the histopathological changes of the liver (proportion of fatty liver lesion site and change of hepatocellular diameter) and are shown in Table 10. It was.

TABLE 10

As can be seen in Table 10, Example 2 according to the present invention, compared to the high fat diet group (2) that caused liver damage, significantly inhibited the increase of fat degeneration and hepatocytes, and therefore, the high fat diet It can be seen that the liver protective effect that can be caused by the very good. On the other hand, the comparison group is similar to the high fat diet group (2) as in 1) it can be seen that the liver damage caused by simvastatin administration.

Experimental Example 4 Total Cholesterol and Neutral Lipid Changes According to Administration of the Extract of the Present Invention

1) A hyperlipidemic model of mice induced by ingestion of high fat feed 45% kcal high fat pellet feed (D12451; Diet research, PA, USA) was used to confirm the inhibition of total cholesterol and triglyceride production according to the present invention.

Experimental method is 173.07mg / g of the extract obtained in Example 2 of the present invention (Cathum Suyeongmyeong Sucu ^® composition) every day according to the weight measured by measuring the body weight at a weekly interval for 84 days from one week after high fat feed supply Diluted to 20ml orally administered once at 20ml / kg and measured total cholesterol and triglyceride changes in blood.

In the same manner as the method described above, the HMG Co A was measured daily by weighing the body weight at a weekly interval for 84 days from the first week after the high fat feed and at the same time as the high fat pellet feed (D12451; Diet research, PA, USA). Simulstatin 10mg / kg, a reductase inhibitor, was orally administered with a high-fat diet at a concentration of 10ml / kg, and the total cholesterol and triglycerides in blood were compared with the high-fat diet group (2) administered only high-fat diet. Table 11 shows.

TABLE 11

As can be seen in Table 11, Example 2 according to the present invention not only significantly suppressed the formation of total cholesterol and triglycerides in blood even when administered with a high fat diet, but also used a combination of high fat feed and simvastatin, an HMG Co A reductase inhibitor. It can be seen that inhibiting the production of total cholesterol and blood triglycerides in the blood than the comparison group administered, the composition according to the present invention can be useful in the treatment of hyperlipidemia and at the same time prevent liver damage that can be caused by the intake of high-fat stone It was.

2) In order to confirm the inhibition of total cholesterol and triglyceride production according to the present invention 1) ICR mice induced by the intake of experiments and other high fat diets (40% beef tallow AIN-76A rodent diet, Dyets Inc., PA, USA) It was measured using the hyperlipidemia model. At the same time with high-fat feed, the extract obtained in Example 3 of the present invention (Byeongmyeong-Su ^® Gold Composition) was diluted daily to 113.2mg / 10ml as a total crude drug dose and administered once orally at a concentration of 10ml / kg each day for 84 days. At sacrifice, changes in total cholesterol and triglyceride content were measured.

In the same way as the method described above, 10 ml / mg of HMG Co A reductase inhibitor simvastatin 10 mg / kg was measured daily according to the weight measured by measuring the body weight at a weekly interval for 84 days from the one-week supply of the high-fat feed at the same time as the high-fat feed. The high-fat diet was administered orally with a high-fat diet, and the high-fat diet group (1) administered only the high-fat diet was compared with the total cholesterol and triglycerides in the blood.

TABLE 12

As can be seen in Table 12, Example 3 according to the present invention not only significantly inhibited the formation of total cholesterol and triglycerides in the blood even when administered with a high fat diet, but also used a combination of high fat feed and simvastatin, an HMG Co A reductase inhibitor. The composition according to the present invention can be useful for the treatment of hyperlipidemia and at the same time preventing liver damage that may be caused by the ingestion of high fat stone. It was confirmed.

Experimental Example 5 Changes in LDL and HDL Contents in Blood According to Administration of Extract of the Invention

1) In order to evaluate the changes in the low density lipoprotein (LDL) and high density lipoprotein (HDL) content of blood according to the administration of the extract of the present invention was measured in the same manner as in 1) . The results are shown in Table 13.

TABLE 13

As can be seen from Table 13, Example 2 of the present invention (Cask Bow Myung Sukyu ^® composition) not only significantly inhibited blood LDL production even when administered with a high fat diet, but also increased the HDL level in the blood to ingest high fat grains. In addition to preventing liver damage that may be induced by the present invention, it was confirmed that it may be useful for treating hyperlipidemia.

In addition, the present invention significantly suppressed LDL production in the blood compared to the control group co-administered with high-fat diet and HMG Co A reductase inhibitor simvastatin, and found that it can be usefully used as an antihyperlipidemic drug by increasing blood HDL levels. Can be.

2) In order to confirm the change evaluation of low density lipoprotein (LDL) and high density lipoprotein (HDL) content in blood according to the administration of the extract of the present invention in the same manner as 2) of Experiment 4 Experimental measurements were taken. The results are shown in Table 14.

TABLE 14

As can be seen in Table 14, Example 3 of the present invention (Byeongmyung-Su ^® Gold Composition) not only significantly inhibited blood LDL production even when administered with a high fat diet, but also increased HDL levels in the blood to ingest high fat grains. It has been confirmed that it may be useful for treating hyperlipidemia at the same time as preventing liver damage that may be caused by.

In addition, the present invention inhibited blood LDL production to a similar degree compared to the comparison group administered with a combination of high fat feed and HMG Co A reductase inhibitor simvastatin, and can be usefully used as a therapeutic agent for hyperlipidemia equal to or higher by significantly increasing blood HDL levels. It can be seen.

Claims (9)

A pharmaceutical composition for preventing and treating liver damage caused by a high fat diet containing clove extract as an active ingredient. The method for preventing and treating liver damage caused by a high fat diet according to claim 1, further comprising a mixed herbal extract of health, cinnamon, nutmeg, sun medicinal herbs, dermis, creation, groceries, corolla and red pepper as active ingredients. Pharmaceutic composition. The pharmaceutical composition for preventing and treating liver damage caused by a high fat diet according to claim 2, further comprising a mixed herbal extract of five drops, fruit and licorice as an active ingredient. The extract according to any one of claims 1 to 3, wherein the extract can be formulated into a formulation such as liquids, pills, tablets, capsules, suspensions, syrups, etc. Pharmaceutical composition for the prevention and treatment of liver damage, characterized in that the extract using the spray drying method. Hepatoprotective agent that protects the liver damaged by hyperlipidemia drug treatment at the same time as treating hyperlipidemia containing clove extract as an active ingredient. Hepatoprotective agent that protects the liver damaged by hyperlipidemia treatment while treating hyperlipidemia, which contains mixed herbal extracts of clove, health, cinnamon, nutmeg, sunscreen, dermis, creation, thick pepper, Hyunho color and red pepper as active ingredients . Cholesterol, health, cinnamon, nutmeg, sunscreen, dermis, creation, thick, Hyunho-red, red pepper, five drops, fruit and licorice mixed with herbal extracts, characterized in that the treatment of hyperlipidemia, simultaneously with the treatment of hyperlipidemia Liver protector to protect the liver. A therapeutic agent for hyperlipidemia, characterized in that it contains a mixed herbal extract of clove, health, cinnamon, nutmeg, sun medicinal, dermis, creation, thick, red pepper and red pepper as active ingredients. A therapeutic agent for hyperlipidemia, characterized in that it contains a mixed herbal extract of cloves, health, cinnamon, nutmeg, sun medicinal herbs, dermis, cultivation, grommets, red pepper, chilli, five drops, fruit and licorice as an active ingredient.