KR100637867B1 - Composition comprising Schizandrae Fructus extract for treatment of diabetes - Google Patents

Abstract

The present invention relates to a diabetic composition comprising the Schizandra chinensis extract as an active ingredient.

Schisandra chinensis extract of the present invention improves the action of insulin in 3T3-L1 adipocytes increases the amount of GLUT 4 of the cell membrane and increases the absorption of glucose, it is excellent in hypoglycemic effect.

Therefore, the composition of the present invention can be usefully used for the prevention and treatment of diabetes mellitus, in particular excellent in the therapeutic effect against insulin-independent diabetes (type 2 diabetes).

Description

Composition comprising Schizandrae Fructus extract for treatment of diabetes             

1 is a diagram showing the degree of glucose uptake according to insulin concentration in 3T3-L1 adipocytes.

Figure 2 is a diagram showing the degree of glucose uptake when 3μ3-L1 adipocytes treated with 0.3 μg / ml of the extract of Schizandra chinensis of the present invention and 1 ng / ml of insulin.

Figure 3 is a diagram showing the degree of glucose uptake when the 3T3-L1 adipocytes treated with 3μg / ㎖ extract of Schisandra chinensis extract of the present invention and 1ng / ㎖.

Figure 4 is a diagram showing the GLUT4 amount of the cell membrane when the Schizandra chinensis extract fraction of the present invention in 3T3-L1 adipocytes.

The present invention relates to a diabetic composition comprising the Schizandra chinensis extract as an active ingredient.

Diabetes mellitus is a non-infectious chronic disease, in which the insulin secreted from the pancreatic β cells is insufficient or does not function properly, so glucose is not used as an energy source in the body and remains high in blood and excreted in the urine.

Diabetes is largely divided into insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). Are classified.

Type 1 diabetes is a condition in which the pancreatic β cells are degraded due to genetic causes, viral infections, and the like, and insulin is hardly secreted. The type 1 diabetes is mainly caused in the tens to twenties, and is also referred to as pediatric diabetes.

Type 2 diabetes is caused by family history, obesity, stress, eating errors or drugs that antagonize with insulin, and is well-known after the age of 40, also known as adult diabetes. Insulin secretion is sufficient in the pancreas, but blood glucose is not normalized despite hyperinsulinemia due to differences in insulin resistance and glucose utilization from normal individuals.

In Korea, more than 90-95% of diabetics are type 2 diabetics.

Symptoms of diabetes are diverse, but the most common ones are polyuria, multiply, and multiply. Due to high blood sugar, glucose and excess water are excreted in the urine by osmotic pressure, resulting in polyuria. As a result, dehydration causes severe thirst, and then you feel hunger and eat a lot of food. In the case of diabetics, glucose is not used as an energy source and thus consumes already stored proteins and fats as energy sources, resulting in weight loss due to a vicious cycle of these phenomena. However, these symptoms are only acute symptoms that occur early in the onset of diabetes.

Diabetes is classified in oriental medicine as Samso (三 消), and divided into upper (small), small (medium), calcined (下 消), the causes of lung fever (肺熱), stomach fever (胃熱), It is largely classified as fever.

Appeal is also called Sogal (小 渴), the deep heart (사 虛) is transferred to the lungs (번 火) to pulsate the chest, red tongue, dry lips, alternately (다음) as a result )

Small and medium is the main symptom of polyuria and multi-diet, the weight loss and constipation due to the vicious cycle of multi-urea and multi-diet.

Calcination is also called senso (腎 消), gugal is less than the appeal, the urine volume is high and the vein is weak.

If you have a severe thirst, it is better to cure it. If you have less thirst and lose weight rapidly, then you've progressed to calcination.

Diabetes can be cured if detected early, and early treatment can prevent complications.

Early detection of diabetes is finding a glucose intolerance. Glucose intolerance is an intermediate stage between normal and diabetic patients, before the onset of diabetes. In other words, the ability of the pancreatic beta cells to control blood sugar and secrete insulin is reduced, or insulin resistance is reduced, and the ability to transport glucose to cells is reduced.

If the treatment of diabetes is delayed and becomes chronic, complications will lead to chronic vascular disease. Diabetic retinopathy (blindness, blindness, retinal hemorrhage), diabetic nephropathy, diabetic peripheral neurosis and Sensory function is reduced.

Currently used diabetic drugs are roughly divided into oral hypoglycemic agents and insulin injections. In general, insulin-independent diabetic patients who have no insulin secretion in the body, gestational diabetic patients, or insulin-independent diabetic patients who are unable to control their blood sugar with oral hypoglycemic agents are given insulin injections, despite the combination of diet and exercise therapy. It is common practice to take oral hypoglycemic agents in patients with insulin-independent diabetes who do not have adequate glycemic control.

Commonly used oral hypoglycemic agents include sulfonylureas, biguanides, and thiazolidinedione.

Sulfonylurea-based drugs include glypizide, glyclazide, glyquidone, glybenclamide, chlorpropamide, and the like, which promote insulin secretion in the pancreas. Therefore, there is a problem that they can not be used in insulin-dependent diabetes patients with no insulin secretion in the pancreas, insulin-independent diabetes patients with relatively reduced insulin secretion in the pancreas, women of childbearing age. In addition, these drugs can cause hypoglycemia when administered overdose or on an empty stomach, and also have side effects such as skin rash, jaundice, anorexia, nausea (nausea) and diarrhea. In particular, long-lived drugs such as chlorpropamide (12-36 hours) have a high risk of hypoglycemia due to accumulation in the body. In addition, since most sulfonylurea-based drugs are metabolized in the liver and excreted in the kidney, they should be used with caution in patients with hepatic and renal dysfunction.

Biguanide-based drugs include metformin and the like, but the mechanism of action is not accurate, but it has been found that there is no effect of increasing insulin secretion in the pancreas, and decreases glucose neosynthesis in the liver. Biguanide-based drugs have a weaker hypoglycemic effect than sulfonylureas, but are less likely to cause hypoglycemia. However, due to the high incidence of side effects of the digestive system, nausea, vomiting, diarrhea and rash appear at the beginning of treatment, and cause life-threatening side effects by causing lactic acidosis. have.

Thiazolidinedione-based drugs have been recently developed and have an effect of improving insulin resistance.

In addition, there are drugs of the acarbose family that interfere with the digestion of carbohydrates after carbohydrate intake and thus raise blood sugar levels. Acarbose drugs are alpha-glucoamylase inhibitors that reversibly inhibit alpha-D-glycosidase activity and are known to inhibit the activity of maltase present in the mucosa of small intestine cells. However, in fact, acarbose is known to have a weak effect of inhibiting maltose degradation and to strongly inhibit the breakdown of sugar.

On the other hand, currently used herbal medicines are prescribed differently depending on the triglycerides of diabetes. Ginseng Baekho-tang (gypsum, gimmo, ginseng, licorice) that heats the lungs and lowers the heat of the lungs when the lungs are red and thirsty. , Jeonsibaekchultang (Geungalgeun, Ginseng, Baekchul, Baekbokyeong, Mokhyang, Kwakhyang, Licorice) and Kangsimtang (처방 心 湯) is prescribed.

There is a heat in the stomach, so it is indigestible and the stool is hard to urinate, but it is not cool in small and medium sized Jowiseunggi-tang (Rhubarb, forget-me-not, licorice), Dongjingamroum (Yanggye, Hwangbaek, Hwanggi, Jimo, Seo Hong-hwa, Siho) Etc.) and pure acid (順 氣 散) are prescribed.

The heat of the gods, lack of fresh water, dry essence, less thirst, but less chilly, but the calcination of the six-season yellow hwan (Sookji-hwang, medicinal herbs, Baekbok-ryeong, Omija, Taxa), and Shin Ki-hwan. Prescribe.

However, the onset of diabetes mellitus, small, medium, and calcined may occur separately, but most of the diabetic patients, these three small all at once. Therefore, in the case of the conventionally used herbal medicines such as the most cases that can not effectively treat the diabetic patients that Samson is at once.

In addition, reducing insulin resistance, increasing insulin secretion and disrupting carbohydrate digestion may improve diabetes, and strict blood sugar control may prevent or delay the development of diabetic complications. Drugs that are effective in the treatment of diabetes are lacking in strict blood sugar control or prevention of complications of diabetes, and the development of new therapeutics is required.

On the other hand, Schizandrae Fructus is a deciduous broad-leaved vine whose leaves are alternate, ovate or obovate, with sharply pointed, serrated, and somewhat hairy on the back veins. Flower is reddish white and blooms in June ~ July. Fruits are used for food and hang on the ends of branches. They ripen red in August-September. Fruits are called Schisandra (Fructus) and Schizandrae Fructus. Fruits include: chizandrol, chizandrin A, B, C, angeloylgomisin O, P, epigomisin, pregomoisin, deoxyschizandrin ), And the like. Omiza has been used in herbal medicine as a raw material of herbal medicine for a long time since it has medicinal effects such as convergence, nourishment, tonic, ginhae medicine, Hajudok, thirst, convergence shovel, ripe ginjin, bosin salt.

Therefore, the inventors of the present invention, while studying a substance for increasing insulin secretion, confirmed that the effect of improving insulin action in Schizandra chinensis extract was completed the present invention.

The present invention is to provide a composition for treating diabetes as an active ingredient Schizandra extract.

The present invention provides a composition for treating diabetes mellitus, Schizandra chinensis extract.

The composition of the present invention includes medicines and health foods useful for the prevention and treatment of diabetes.

Hereinafter, the present invention will be described in detail.

Preparation method of Schizandra chinensis extract of the present invention is as follows.

Schisandra chinensis rinse with water and dry in the shade. Dry Schizandra chinensis in 70% ethanol and extract twice over 2 hours. The ethanol extract was filtered and centrifuged at 2000 rpm, the supernatant was concentrated under reduced pressure in a rotary vacuum concentrator, and lyophilized to produce an extract powder sample.

The extracted powder sample was suspended in water, and then expanded by adding methanol, and subjected to column chromatography filled with Amberlite XAD-4 gel while changing the polarity of the eluent. ), 20% methanol fraction (Fr.2), 40% methanol fraction (Fr.3), 60% methanol fraction (Fr.4), 80% methanol fraction (Fr.5) and 100% methanol fraction (Fr.6) ), And each fraction is concentrated under reduced pressure at low temperature and then lyophilized.

The Schizandra chinensis extract fraction of the present invention enhances the action of insulin in 3T3-L1 adipocytes to increase glucose uptake. That is, when 0.3 μg / ml of Schisandra chinensis fraction was treated with 1 ng / ml of insulin, 60% methanol fraction (Fr. 4) and 80% methanol fraction (Fr. 5) increased glucose uptake. In particular, the 80% methanol fraction (Fr. 5) increased the glucose uptake more than the insulin treatment at 50 ng / ml, which is statistically significantly higher than that of the insulin-only control group.

In addition, when the amount of Schisandra chinensis fraction was increased to 3 µg / ml and treated with 1 ng / ml of insulin, 20% methanol fraction (Fr. 2), 60% methanol fraction (Fr. 4), 80% methanol fraction Increased glucose uptake in stroke (Fr. 5) and 100% methanol fraction (Fr. 6), especially 60% methanol fraction (Fr. 4), 80% methanol fraction (Fr. 5) to insulin 50 ng / ml Glucose uptake was increased more than when treated, which was statistically significantly higher than that of the control group treated with insulin only.

In addition, the 60% methanol fraction (Fr.4) and 80% methanol fraction (Fr.5) of the Schizandra chinensis extract fractions enhance insulin signal transduction system to enhance insulin action, thereby increasing the amount of GLUT 4 present in the cell membrane. It appears highest and increases insulin to the extent that 50 ng / ml is treated. Increasing GLUT 4 in the cell membrane is closely related to increasing glucose uptake.

Therefore, the composition of the present invention can be usefully used for the prevention and treatment of diabetes.

The composition of the present invention may contain one or more active ingredients exhibiting the same or similar function in addition to the Schizandra chinensis extract.

The Schizandra chinensis extract may be administered orally or parenterally during clinical administration and may be used in the form of a general pharmaceutical preparation. That is, the Schizandra chinensis extract of the present invention may be administered in various oral and parenteral formulations during actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants that are commonly used, or Formulated using excipients. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and the like, which are included in the Schizandra chinensis extract at least one excipient such as starch, calcium carbonate, sucrose, lactose and gelatin, etc. Are mixed to prepare. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups, and may include various excipients such as wetting agents, sweeteners, fragrances and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and 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, glycerol, gelatin and the like can be used.

Dosage units may contain, for example, one, two, three or four times the individual dosage, or they may contain 1/2, 1/3 or 1/4 times. The individual dosage preferably contains an amount in which the effective drug is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose. The effective dose of Schizandra chinensis extract is 50-300 mg / kg, preferably 70-150 mg / kg, and may be administered 1-6 times a day.

As a result of oral administration of Schisandra chinensis extract of the present invention to rats, 50% lethal dose (LD ₅₀ ) by oral administration toxicity test is determined to be a safe substance of at least 1 g / kg or more.

The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of diabetes.

The composition of the present invention may be added to health foods for the purpose of improving diseases caused by diabetes. When the Schizandra chinensis extract of the present invention is used as a food additive, the Schizandra chinensis extract may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). Generally, in the preparation of foods or beverages, the Schizandra extract of the present invention is added in an amount of up to 15% by weight, preferably up to 10% by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. .

There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 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, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid. Carbonating agents and the like used in beverages. In addition, the composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred examples and experimental examples are presented to help understand the present invention. However, the following Examples and Experimental Examples are provided only to more easily understand the present invention, and the contents of the present invention are not limited by the Examples.

Example

Schisandra chinensis was purchased at Gyeongdong Market in Seoul, washed with water, and dried in the shade. 1 kg dried Schizandra chinensis was added to 10 L of 70% ethanol and extracted twice for 2 hours. The ethanol extract was filtered through reds, centrifuged at 2000 rpm, the supernatant was concentrated under reduced pressure in a rotary vacuum concentrator, and lyophilized to produce an extract powder sample.

The extracted powder sample was suspended in water, and then expanded by adding methanol, and subjected to column chromatography filled with Amberlite XAD-4 gel while changing the polarity of the eluent. ), 20% methanol fraction (Fr.2), 40% methanol fraction (Fr.3), 60% methanol fraction (Fr.4), 80% methanol fraction (Fr.5) and 100% methanol fraction (Fr.6) ), And each fraction was concentrated under reduced pressure at low temperature and then lyophilized.

Each fraction was used dissolved in 1 mg / ㎖ in DMSO.

Experimental Example 1  : Effect of Schizandra chinensis Extract of the Present Invention on Glucose Uptake into Adipocytes

In order to determine the effect of the Schizandra chinensis extract of the present invention on glucose uptake into adipocytes, the following experiment was performed.

1. Cell Culture

The 3T3-L1 cells used in the experiment were purchased from the American Cell Line Bank, and added DMEM with 1% fetal bovine serum (FBS), gentamycine (100 units / ml) and streptomycin (streptomycin (100 µg / ml)). Cultured in (Dulbecco's modified Eagle's medium) medium.

For 3T3-L1 fibroblasts, wash the surface of the cultured cells with phosphate buffer solution every three days after incubation, add 1 ml of 0.25% trypsin-EDTA solution per 50 ml flask, treat at room temperature for 1 minute, and discard the trypsin solution. Cells were detached and subcultured by storing at 5 ° C. for 5 minutes. The detached cells were suspended in 10 ml of DMEM medium added with 10% FBS, and then transferred to a new culture vessel (50 ml culture flask), and the CO ₂ incubator (37 ° C., 5% CO) had a split ratio of 1:20. ₂ ) were incubated.

2. Glucose uptake into adipocytes

3T3-L1 fibroblasts were incubated until fully confluent in the same manner as the passage. After 2 days of filling the bottom of the culture vessel, incubated with 0.25 μM of derivatized dexamethasone (dexamethasone) for 3 days and incubated for 3 days, and then changed into high-density glucose DMEM solution every 2 days for 10-15 days. Glucose uptake experiment was performed in between.

The number of adipocytes in the culture vessel was counted and dispensed so that the wells of the 12 well plates could be completely filled without empty space. Adipocytes transferred to well plates were washed with PBS and incubated for 30 minutes at 37 ° C. in HEPES solution after 12 hours in DMEM containing low concentrations of glucose containing 1% bovine serum albumin. . 1 μ Ci / ml of [ ¹⁴ C] 2-deoxyglucose and 1 mM glucose were added and incubated at 22 ° C. for 30 minutes to determine the degree of glucose uptake into cells by the amount of ¹⁴ C transferred into cells.

In order to rule out nonspecific glucose uptake, the amount of glucose transported into the cell was measured by subtracting the glucose shift when incubated with cyto B, which inhibits the action of glucose transporter 4 (GLUT4). .

Cells were washed with PBS containing 10 mM glucose and digested with 0.5N NaOH. The lysed cells were neutralized with acetic acid and the content of ¹⁴ C was measured by beta counter (Tri-Carb 2100TR, Packard Bioscince, IL).

3. Effect of Schizandra chinensis Extract Fraction on Glucose Absorption

In order to examine whether each fraction of Schizandra chinensis contains insulin sensitive agent, the Schizandra chinensis extract prepared in the above Example was dissolved in DMSO at 1 mg / ml, and then diluted to 0.3 and 3 µg / ml in PBS. Glucose uptake was measured at two concentrations.

Each fraction with 1 ng / ml insulin was added to 3T3-L1 adipocytes and incubated for 1 hour. The glucose uptake was compared with the result at 50 ng / ml insulin.

Insulin 0 (base), 1, 3, 5, 10, 25, 50, 75 ng / ml was used as a control.

All experiments were repeated three times, and the results were expressed as the ratio of the values of no treatment of both insulin and Schizandrae extract fractions.

In addition, the insulin uptake effect of Schizandra chinensis extract may be due to the specific action of insulin, or if it is non-specifically acting as a solvent to the cell to move glucose into the cell. The degree of absorption of glucose was measured in the state of adding only Schisandra chinensis extract without adding.

This value is based on the measurement of glucose uptake with the Schizandra chinensis extract at 0 ng / ml to rule out that the Schizandra chinensis extract acts as a solvent regardless of the action of insulin to destroy cell membranes and increase glucose uptake. Anything above the basal value was considered to have no action as an insulin sensitive agent even though it increased glucose uptake.

The results were expressed as mean ± standard deviation, and the increase in glucose uptake in the 3T3-L1 adipocytes compared to the control group of the Schizandra chinensis extract was measured using only 1ng / ml insulin and 1ng / ml of insulin and Schizandra chinensis extract. The fractions were put together and the measured values were verified by two sample t-test method. The significance test of all statistical treatments was set at α = 0.05.

Measurement of glucose uptake according to insulin concentration in 3T3-L1 adipocytes is shown in FIG. 1.

When the 3T3-L1 adipocytes were treated with insulin 1ng / ml and the extract of Schizandra chinensis extract 0.3μg / ml of the present invention, the degree of glucose uptake was shown in FIG. 2.

When the 3T3-L1 adipocytes were treated with insulin 1ng / ml and the extract of Schizandra chinensis extract 3μg / ml of the present invention, the degree of glucose uptake was measured in FIG. 3.

As shown in FIG. 1, glucose uptake increased as insulin concentration increased up to 25 ng / ml insulin, but at insulin concentration higher than 25 ng / ml glucose uptake into cells did not differ according to insulin concentration.

As shown in FIG. 2, when 0.3 μg / ml Schizandrae extract fraction was treated with 1 ng / ml insulin, 60% methanol fraction (Fr.4) and 80% methanol fraction (Fr.5) increased glucose uptake. I was. In particular, the 80% methanol fraction (Fr.5) increased glucose uptake more than 50 ng / ml of insulin.

As shown in Figure 3, the amount of Schisandra chinensis extract was increased to 3 μg / ml and treated with 1 ng / ml of insulin, 20% methanol fraction (Fr.2), 60% methanol fraction (Fr.4). , Glucose uptake was increased in 80% methanol fraction (Fr. 5) and 100% methanol fraction (Fr. 6). In particular, the 60% methanol fraction (Fr. 4) and 80% methanol fraction (Fr. 5) increased glucose uptake more than 50 ng / ml of insulin.

Therefore, it can be seen that insulin action is greatly improved in the 60% methanol fraction (Fr. 4) and the 80% methanol fraction (Fr. 5) of Schizandra chinensis.

At this time, it can be seen that the glucose absorption value in the state containing only the Schizandra chinensis extract is similar to or rather low than the base value, so that the fraction does not act to increase the absorption of glucose nonspecifically.

4. Changes in the amount of GLUT 4 present in the cell membrane

After 3T3-L1 adipocytes were transferred to 10 cm 2 plates, 3T3-L1 adipocytes were incubated for 12 hours in high glucose DMEM with 3% bovine serum albumin instead of plasma, followed by addition of 3 μg / ml Schisandra chinensis extract. After incubation for 5 hours, 0, 1 or 50 ng / ml of insulin was treated for 5 minutes. Adipocytes were stopped with cold PBS and immediately consisted of 20 mM tris (pH 7.4) containing 2 mM EDTA, 137 mM NaCl, 1% NP ₄ 0, 10% glycerol and 12 mM alpha-glycerol phosphate and protease inhibitors. Cells were eluted with lysis buffer. The cell eluate was left in ice for 30 minutes and the cell membrane was separated by Kotani et al. The protein content of the isolated cell membrane was measured by Lowry method, and the glucose transporter 4 (GLUT 4) content in the same amount of membrane protein was immunoblotting using anti-GLUT 4 antibody (Chemicon, Temecula, CA). It was measured by the method.

The results are shown in FIG.

As shown in FIG. 4, the 60% methanol fraction (Fr. 4) and 80% methanol fraction (Fr. 5) of 3 μg / ml of Schizandra chinensis were applied to the cell membrane when treated with 1 ng / ml insulin. The amount of GLUT 4 was the highest and increased up to 50 ng / ml of insulin. The 60% methanol fraction (Fr.4) and 80% methanol fraction (Fr.5) of Schisandra chinensis improved the insulin signal transduction system, enhancing insulin action, and increasing the amount of GLUT 4 in the cell membrane.

Therefore, it can be seen that the increase of GLUT 4 of the cell membrane is closely related to the increase of glucose uptake.

Experimental Example 2  : Acute Toxicity of Oral Administration in Rats

In order to determine the acute toxicity of the composition of the present invention, the acute toxicity test was carried out in the following manner.

Acute toxicity test was conducted using 6-week-old specific pathogen-free (SPF) SD rats. Two animals per group were suspended orally administered once at a dose of 1 g / kg / ml in a composition of the present invention suspended in 0.5% methylcellulose solution, respectively. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed. Necropsy was performed to observe abdominal and thoracic organ abnormalities.

As a result, no significant clinical symptoms or dead animals were noted in all animals treated with the test substance, and no toxic changes were observed in weight changes, blood tests, blood biochemical tests, and autopsy findings.

Therefore, the compositions of the present invention do not show a change in toxicity even in rats up to 1 g / kg, oral administration minimum dose (LD ₅₀ ) was determined to be a safe substance of at least 1 g / kg or more.

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

Formulation Example 1  : Preparation of Pharmaceutical Formulations

1. Preparation of powder

Schizandra chinensis extract 2g

1g lactose

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

2. Preparation of Tablets

Schisandra extract 100mg

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

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

3. Preparation of Capsule

Schisandra extract 100mg

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

Formulation Example 2  : Manufacture of food

Foods containing the Schisandra chinensis extract of the present invention were prepared as follows.

1. Preparation of Cooking Seasonings

Schisandra chinensis extract 20-95% by weight of the present invention was prepared for cooking spices for health promotion.

2. Preparation of Tomato Ketchup and Sauce

The tomato ketchup or sauce for health promotion was prepared by adding 0.2-1.0 wt% of Schizandra extract of the present invention to tomato ketchup or sauce.

3. Manufacturing of Flour Foods

0.5 ~ 5.0% by weight of Schizandra chinensis extract of the present invention was added to the flour, and using the mixture to prepare bread, cakes, cookies, crackers and noodles to prepare foods for health promotion.

4. Preparation of soups and gravy

0.1-5.0% by weight of Schizandra chinensis extract of the present invention was added to soups and broths to prepare meat products for health promotion, soups and noodles for noodles.

5. Preparation of Ground Beef

10 wt% of Schisandra chinensis extract of the present invention was added to ground beef to prepare a ground beef for health promotion.

6. Manufacture of Dairy Products

5 to 10% by weight of Schizandra chinensis extract of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

7. Manufacture of wire

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh using a grinder.

Black beans, black sesame seeds, and perilla were also steamed and dried by a known method, and then ground to a powder having a particle size of 60 mesh.

The Schizandra chinensis extract of the present invention was decompressed and concentrated in a vacuum concentrator, and the dried product obtained by drying with a sprayer or a hot air dryer was pulverized with a particle size of 60 mesh to obtain a dry powder.

It was prepared by combining the dry powder of the grains, seeds and Schisandra chinensis extract prepared in the following ratio.

Cereals (30% by weight brown rice, 15% by weight radish, 20% by weight barley),

Seeds (7% by weight perilla, 8% by weight black beans, 7% by weight black sesame),

Dry powder of Schizandra chinensis extract (3% by weight),

Ganoderma lucidum (0.5% by weight),

Foxglove (0.5 wt%)

Formulation Example 3  : Preparation of Beverages

1. Preparation of Carbonated Drinks

5-10% of sugar, 0.05-0.3% citric acid, 0.005-0.02% caramel, 0.1-1% of vitamin C are mixed, and 79-94% purified water is mixed to make syrup, and the syrup is 85-98 Sterilizing at 20 ℃ for 180 seconds to mix with a cooling water 1: 1 ratio and then injected carbon dioxide gas 0.5 ~ 0.82% to prepare a carbonated beverage containing Schizandra extract of the present invention.

2. Manufacture of health drinks

Instant sterilization by homogeneously mixing minor ingredients such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), water (75%) and Schizandra chinensis extract Health drinks were prepared by packaging in small packaging containers such as plastic bottles.

3. Preparation of Vegetable Juice

5 g of Schisandra chinensis extract of the present invention was added to 1,000 ml of tomato or carrot juice to prepare a vegetable juice for health promotion.

4. Preparation of Fruit Juice

1 g of Schizandra chinensis extract of the present invention was added to 1,000 ml of apple or grape juice to prepare fruit juice for health promotion.

Schisandra chinensis extract of the present invention improves the action of insulin in 3T3-L1 adipocytes increases the amount of GLUT 4 of the cell membrane and increases the absorption of glucose, it is excellent in hypoglycemic effect.

Therefore, the composition of the present invention can be usefully used for the prevention and treatment of diabetes mellitus, in particular excellent in the therapeutic effect against insulin-independent diabetes (type 2 diabetes).

Claims (6)

Pharmaceutical composition for the treatment of diabetes mellitus with Schizandra chinensis extract. The pharmaceutical composition for treating diabetes of claim 1, wherein the Schisandra chinensis extract is a fraction obtained by extracting with 70% ethanol and then gradient gradient with 0-100% aqueous methanol solution. The pharmaceutical composition for treating diabetes of claim 2, wherein the extract of Schizandra chinensis is 60% methanol fraction (Fr. 4), 80% methanol fraction (Fr. 5). Health food for the prevention and improvement of diabetes mellitus with Schizandra chinensis extract. The method of claim 4, wherein the Schizandra chinensis extract is extracted with 70% ethanol, and the fraction obtained by concentration gradient with an aqueous solution of 0-100% methanol, diabetes prevention and improvement health foods. The method of claim 5, wherein the Schizandra extract fraction is 60% methanol fraction (Fr. 4), 80% methanol fraction (Fr. 5) characterized in that diabetes prevention and improvement health food.

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