KR100875247B1 - Composition for preventing and treating metabolic diseases comprising the extract of lysimachiae foenum-graeci herba - Google Patents

Abstract

A pharmaceutical composition is provided to prevent and treat the metabolic disease such as hyperlipidemia or fatty liver by using an extract of Lysimachiae foenum-graeci Herba. A pharmaceutical composition for preventing and treating the metabolic disease contains an extract of Lysimachiae foenum-graeci Herba as an effective ingredient. Preferably the composition is in form of a capsule, a tablet, a granule, a powder or a drink.

Description

Composition For Preventing And Treating Metabolic Diseases Comprising The Extract Of Lysimachiae Foenum-Graeci Herba}

The present invention relates to a prophylactic and therapeutic agent for metabolic diseases containing the extract of Lysimachiae Foenum-Graeci Herba as an active ingredient, and more specifically, to reduce blood sugar levels, triglycerides and cholesterol levels, AST and ALT levels, The present invention relates to the prevention and treatment of various metabolic diseases including diabetes, hypertension, fatty liver, cardiovascular disease and hyperlipidemia by reducing liver fat, and raw materials, functional foods, and herbal medicines as liver protection agents.

 The recent improvement of living standards due to economic development improves the hygiene environment, frequent intake of instant foods, and changes in eating-oriented diets cause excessive accumulation of calorie energy in the body. However, such changes in dietary life of modern people have also led to a decrease in calorie energy consumption due to lack of exercise, leading to a rapid increase in the obese population.

As such, the calorie energy accumulated in the body is expressed not only in obesity but also in various disease forms, such as metabolic diseases and metabolic syndrome including diabetes, hyperlipidemia, fatty liver, and the like.

Diabetes is a systemic metabolic disease caused by genetic and environmental factors. It is a condition caused by the absolute or relative lack of insulin in the body and refers to an abnormally high blood sugar level. Complications of diabetes include hypoglycemia, ketoacidosis, hyperosmolar coma, macrovascular complications, diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy.

Hyperlipidemia refers to both hypercholesterolemia and hypertriglyceridemia and refers to an increase in cholesterol (above 240 mg / dL) and triglycerides (above 200 mg / dL) above the normal range, and is caused by lipoprotein and lipid metabolism disorders. do. Hyperlipidemia is divided into primary hyperlipidemia caused by genetic abnormalities and secondary hyperlipidemia caused by other diseases or drugs such as diabetes. Although there is no particular symptom, the increase in blood cholesterol and triglycerides causes problems such as atherosclerosis, hypertension, and cardiovascular disease.

Fatty liver refers to a state in which fat is accumulated in liver cells. Accumulated fat itself is not toxic to hepatocytes and is not severe. In many cases, there are no symptoms and liver function is usually normal or slightly decreased. However, fatty liver becomes so severe that the fat mass in the liver cells decreases the function of liver cells, including the nucleus. In other words, the accumulated fat in the cells causes the blood vessels and lymph glands in the liver to circulate between the blood vessels and the lymphatic glands, resulting in impaired hepatic function. Bring.

Metabolic syndrome refers to a syndrome that is accompanied by risk factors such as hyperlipidemia, hypertension, abnormal glucose metabolism, and obesity. Recently, the Adult Treatment Program III (ATP III), established by the World Health Organization and the US Institute of Cardiology, Lung, and Blood, was officially named as metabolic syndrome or insulin resistance syndrome.

According to the ATP III of the National Cholesterol Education Program (NCEP), published in 2001, ① abdominal obesity with waist circumference of 40 inches (102 cm) for men and 35 inches (88 cm) for women, ② triglycerides 150 mg / One of five risk factors: dL or higher, ③ HDL cholesterol in men 40 mg / dL, women 50 mg / dL or less, ④ blood pressure 130/85 mmHg or higher, ⑤ fasting glucose in 110 mg / dL or higher. If three or more are indicated as metabolic syndrome. In Asians, when waist circumference is more than 90 centimeters for males and 80 centimeters for females, abdominal obesity is somewhat adjusted. According to the current regulations, Koreans have about 25% of the population with metabolic syndrome. have. Insulin resistance refers to a phenomenon in which even though insulin is normally secreted in the body, the "supply of glucose into cells" does not occur properly. Glucose in the blood cannot enter the cell, resulting in hyperglycemic symptoms. Because of the lack of glucose in the cell to function properly, the symptoms of the metabolic syndrome will eventually appear. Until now, the drug for the treatment of metabolic syndrome has not been developed and attempts to treat the metabolic syndrome using only drugs for treating diabetes, hyperlipidemia and hypertension, but has limitations as a drug. Currently available drugs are metformin, TZD (thiazolidinediones), glucosidase inhibitors, dual PPARγ / α agonist and DDP (Dipeptidyl peptidase) IV inhibitors, which are used as antidiabetic drugs. ApoA-I isoforms, related peptides and CETP (Cholesterol ester transport protein) inhibitors, which are targeted for blood pressure and hyperlipidemia, are also attracting attention.

In the present invention, the above-mentioned diabetes mellitus, hyperlipidemia, fatty liver and arteriosclerosis, hypertension, cardiovascular disease known to occur due to them, and metabolic syndrome in which these diseases occur simultaneously are collectively called "metabolic diseases".

The present invention is to prevent metabolic diseases containing glucose, triglyceride, cholesterol, hepatic enzyme level (AST / ALT) and extract of Lysimachiae Foenum-Graeci Herba as an active ingredient, which is effective in reducing liver fat. And raw materials, functional foods, cosmetics, and herbal medicines as therapeutic agents and hepatoprotectants.

The present invention is characterized by extracts of metabolic disease indicator values (glucose in blood, triglycerides, cholesterol, liver enzymes levels) obtained in Lysimachiae Foenum-Graeci Herba and the effect of reducing fat in liver tissues.

In the present invention in the preparation of Yeongreung (Lysimachiae Foenum-Graeci Herba) extract,

(1) drying and crushing Yeongneung outpost or leaves;

(2) extracting the solvent by adding 5 to 50 times the organic solvent on the basis of the weight of Yeongneung flavor obtained in (1);

(3) filtering the organic solvent extraction solution using a filter paper and then concentrating under reduced pressure at a temperature of 40 ° C. or lower, and separating the extract having the effect of inhibiting adipocyte differentiation, weight and body fat reduction from Yeongneung. to provide.

The organic solvent includes a lower alcohol having 1 to 4 carbon atoms.

The youngneung extract of the present invention provided according to the above method has an excellent effect on reducing metabolic disease index values (blood glucose, triglycerides, cholesterol, liver enzymes levels) and fat in liver tissues, thereby preventing metabolic diseases and It can be used as a raw material for therapeutic agents, functional foods and herbal medicines.

In one embodiment, the extract of the present invention was administered to an obese animal model to observe the metabolic disease indicator levels (blood glucose, triglycerides, cholesterol, liver enzymes levels) and the effect of fat reduction in liver tissue.

The composition of the present invention, the extract based on the total weight of the composition 0.1 to 50% by weight. The composition comprising the Youngnung extract of the present invention may further comprise a suitable carrier, excipient or diluent according to conventional methods. Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Compositions comprising extracts according to the invention are each formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories or sterile injectable solutions according to conventional methods. Can be used. Specifically, when formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, and the like. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid form preparations contain at least one excipient such as starch, calcium carbonate, sucrose ( sucrose), lactose, gelatin and the like can be mixed. In addition to simple excipients, lubricants such as magnesium stearate, talc can also be used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups, and include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Can be. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and suspending agent, 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.

The extract of the present invention may vary depending on the age, sex, and weight of the patient, but in general, an amount of 0.01 to 500 mg / kg, preferably 0.1 to 100 mg / kg, may be administered once or several times a day. Can be. In addition, the dosage of the extract can be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes. All modes of administration can be envisaged, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection. Youngneung extract of the present invention has little toxicity and side effects, so can be used with confidence even for prolonged administration for prophylactic purposes.

The present invention provides a health functional food for the prevention of cerebral nervous system-related anxiety comprising the Yeongneung extract and food acceptable additives. The composition comprising the extract of Yeongreung Hyang of the present invention can be used in a variety of drugs, foods and beverages for the prevention of cerebral nervous system-related anxiety. Foods to which the extract of the present invention may be added include various foods, for example, beverages, gums, teas, vitamin complexes, dietary supplements, and the like, which are pills, powders, granules, tablets, tablets, capsules or beverages. Available in form. At this time, the amount of the extract in the food or beverage, in general, in the health food composition of the present invention can be added to 0.01 to 15% by weight of the total food weight, 0.02 to 10 g, based on 100 ml for the health beverage composition, Preferably it can be added in the ratio of 0.3-1 g.

Food additives as defined herein include food additives customary in the art, such as flavorings, flavors, colorants, fillers, stabilizers, and the like. The health beverage composition according to the present invention is an essential ingredient in the indicated ratio, and there is no particular limitation on the ingredients added to the extract other than the extract, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrin; Conventional sugars such as and the like and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As described above, the extract of Yeongreung (Lysimachiae Foenum-Graeci Herba) according to the present invention has an excellent effect on reducing metabolic disease indicator level (blood glucose, triglyceride, cholesterol, liver enzyme levels) and fat in liver tissue. Therefore, it can be usefully used as a raw material, a functional food, and a herbal medicine as a prophylactic and therapeutic agent for metabolic diseases including diabetes, hyperlipidemia, fatty liver and metabolic syndrome in which they occur simultaneously and as a hepatoprotectant.

Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples. However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example

Example 1 Isolation of the Extract of Lysimachiae Foenum-Graeci Herba

After drying and crushing Yeongneung incense leaves or leaves, 5-50 times the amount of alcohol (such as methanol or ethanol) is added based on the weight of Yeongneung incense (Lysimachiae Foenum-Graeci Herba), and the mixture is extracted under reflux for at least 24 hours. Extracted. Next, the alcohol (methanol or ethanol) extraction solution was filtered using a filter paper, and then concentrated under reduced pressure at a temperature of 40 ℃ or less.

Example 2: Prevention and treatment of metabolic disease in obesity-induced (DIO) mice, obese animal model

C57BL / 6 male mouse 7 weeks of age (obtained from KOATEC Co., Ltd.) purchased at 20 ± 1 ℃ Humidity 50 ± 10% Contrast cycle 12 hours, roughness 150 ~ 300 Lux, ventilation 10 ~ 20 times / hr It was raised in a maintained kennel. Feed was supplied freely by purchasing the experimental animal solid feed (source: Polars International Co., Ltd.) and drinking water was freely ingested after autoclaving the tap water. After 1 week of acclimatization, the feed was fed as a 60% Kcal solid feed from Research Diet, followed by oral administration of Youngneung extract at 30, 100, 300mg / kg / day for 42 days. Sibutramine (10 mg / kg / day) was used as a positive control and 0.5% methyl cellulose (MC) was used as an equal control. The mice treated with the substance for 6 weeks were fasted for 1 day and killed by CO ₂ gas, and blood collected from the abdominal vena cava was placed in an EDTA tube, stored in ice, and centrifuged at 3,000 rpm for 10 minutes. plasma) was analyzed using an automated biochemical analyzer (AU400, Olympus, Japan). In addition, the extracted organs were immediately frozen in liquid nitrogen and stored in a -70 ° C low temperature freezer, and analyzed histologically.

FIG. 1A is a photograph of liver tissue extracted from a control group, a test group and a positive control group, and FIG. 1B is a cryosection of the liver extracted from the control group, a test group and a positive control group, and then hematoxylin- This is a histological picture of the state of liver tissue using the Eosin (Hematoxylin-Eosin) staining method. FIG. 1C is a histological picture of fats distributed in liver tissue using oil-red O staining method after freezing sections of livers extracted from a control group, a test group, and a positive control group. to be. As shown in FIG. 1, the control group showed excessive fat accumulation in hepatocytes by the high-fat diet, but fatty liver appeared, but the test group administered with Yeongneung-hyang extract significantly increased the fat accumulated in hepatocytes compared to the positive control group administered with sibutramine. The improvement was confirmed.

The table below shows the results of analyzing the blood collected. In addition, the triglyceride and cholesterol content in the extracted liver tissue was measured and the results are shown in FIG. 2.

table. Metabolic Disease in Diet-Induced Obesity (DIO) Mice

Indicator measurement

Remarks: Aspartate aminotranferase (AST) Alanine aminotransferase (ALT), Glucose (GLU), Cholesterol (CHO), Triglyceride (TG), Albumin (ALB)

As shown in the table, it was confirmed that the administration of Yeongneung-hyang extract significantly decreased the liver enzymes AST and ALT and blood glucose, cholesterol and triglyceride levels due to the high fat diet. However, ALT and glucose levels in the positive control group treated with sibutramine were significantly decreased, but AST and cholesterol levels were decreased.

The levels did not change and triglyceride levels increased.

In addition, as shown in Figure 2, when administered Yeongneung extract similar to the positive control group, it was confirmed that the liver triglyceride and cholesterol content significantly decreased.

Examples of preparations for the compositions of the present invention are illustrated below.

Formulation Example 1 Preparation of Powder

300 mg of dry powder of Youngneung hyang extract of Example 1

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2: Preparation of Tablet

50 mg of dry powder of Youngneung hyang extract of Example 1

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

50 mg of dry powder of Youngneung hyang extract of Example 1

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

50 mg of dry powder of Youngneung hyang extract of Example 1

Appropriate sterile distilled water for injection

pH adjuster

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation Example 5 Preparation of Liquid

100 mg of dry powder of Youngneung extract of Example 1

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method for preparing a liquid, each component is added and dissolved in purified water, lemon flavor is added, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by adding purified water, and then filled in a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Healthy Food

1000 mg of dry powder of Youngneung extract of Example 1

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

Folate 50 ㎍

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation Example 7 Preparation of Healthy Drinks

Yeongneung-hyang extract dry powder of Example 1 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Lysimachiae Foenum-Graeci Herba extract according to the present invention has an excellent effect on reducing metabolic disease indicator levels (blood glucose, triglycerides, cholesterol, liver enzymes levels) and fats in liver tissues. , Fatty liver and metabolic syndrome, including metabolic syndrome that occurs simultaneously, and can be usefully used as a raw material, functional food and herbal medicine as a hepatoprotectant.

1 is a picture of liver tissue extracted from rats of the control group, the test group, and the positive control group, a picture of hematoxylin-eosin staining of the liver tissue, and fats distributed in the liver tissue. The picture is dyed with O).

Figure 2 is a graph showing the results of measuring the triglyceride and cholesterol content in liver tissue using the liver extracted from the rats of the control group, the test group and the positive control group.

Claims (2)

A pharmaceutical composition for the prevention and treatment of hyperlipidemia or fatty liver, which contains the extract of Lysimachiae Foenum-Graeci Herba as an active ingredient. The pharmaceutical composition of claim 1, wherein the composition is in the form of a capsule, tablet, granule, powder or beverage.

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