KR20070097868A - Composition comprising an allium cepa l. skin extract for preventing and treating diabetes mellitus - Google Patents

Abstract

A composition comprising the extract of Allium cepa L. skin for preventing and treating diabetes mellitus is provided to inhibit activity of alpha-glucosidase and rapid increase of glucose concentration in blood after meal without side effects, so that glucose concentration in blood is reduced. A pharmaceutical or health food composition for preventing and treating diabetes mellitus comprises 0.1-50 wt.% of the extract of Allium cepa L. skin with no toxicity and side effects, is prepared by extracting Allium cepa L. skin with water, C1-C4 lower alcohol including methanol, ethanol and butanol or a mixed solvent thereof, and has daily dosage of 0.0001-100 mg/kg, wherein the health food composition is formulated as powder, granule, tablet, capsule, syrup or beverage.

Description

Composition comprising an Allium cepa L. skin extract for preventing and treating diabetes mellitus}

1 is a diagram showing the inhibitory effect of α-glucosidase (α-glucosidase),

Figure 2 is a diagram showing the effect of postprandial hypoglycemia in diabetic model rats.

The present invention relates to a composition for preventing and treating diabetes containing onion peel extract having a significant hypoglycemic effect as an active ingredient.

Diabetes is a disease caused by abnormally high levels of glucose in humans and mammals, which raises the level of hemoglobin in plasma and chronic hyperglycemia. And a series of complications such as atherosclerosis, microangiopathy, kidney disease, heart disease, diabetic retinopathy and other eye diseases.

Diabetes mellitus is characterized by two types: insulin dependent diabetes (IDDM) is caused by a lack of secretion of insulin, a glucose-regulating hormone in the blood, mainly in the 10s to 20s. It is called juvenile diabetes because it occurs in young people. Type II (non-insulin dependent diabetes, NIDDM) occurs mainly after the age of 40, and occupies most of the diabetic patients in Korea. Unlike type I, it is called adult-type diabetes and the cause of the disease is not clear yet, but it is known to be caused by genetic factors and environmental factors. The etiology of type II diabetes has been observed in both pancreatic beta cells with impaired insulin secretion and in target cells with insulin action (insulin resistance), but it is not yet clear which changes are of primary importance.

Agents currently used for complications such as type II diabetes and insulin resistance include five groups of compounds: biguanides, thiazolidinediones, sulfonylureas, and benzoic acid. Derivative compounds and α-glucosidase inhibitors are used. Among these, biguanide compounds such as metformin are known to prevent excessive blood gluconeogenesis. Thiazolidinedione compounds are thought to act to increase glucose consumption in peripheral nerves, benzoic acids such as sulfonylureas, repaglinide compounds such as tolbutamide and glyburide A-glucosidase inhibitors, such as derivatives and acarbose, act to stimulate insulin secretion and lower plasma glucose.

The sulfonylurea compound cannot be administered to insulin-dependent type I diabetic patients, and non-insulin-dependent type II diabetic patients reduce insulin secretion, abnormal fetal birth, abortion and May cause side effects such as stillbirth. In addition, most sulfonylurea compounds should be administered carefully to patients with impaired liver and kidney function due to the metabolism of sulfonylureas.

Although the mechanism of biguanide-containing preparations such as metformin has not been elucidated, although biguanide compounds are unable to increase pancreatic insulin secretion, they lower blood sugar more effectively than sulfonylureas and the frequency of hypoglycemia induction. low. However, it can cause nausea, vomiting, diarrhea and rash at the beginning of administration, and can cause side effects such as fatal lactic acidosis, so it can be used only as a clinical reagent in the United States.

Since sulfonylurea and biguanide-containing preparations have the above drawbacks and side effects, there is a need for an excellent hypoglycemic agent with low side effects and high safety. To date, there is no cure for diabetes, and there are many studies to search for diabetes treatment from natural products due to the side effects of drug treatment. Use of natural products is highly recommended (Grover JK, Vats. V., Rathi. SS, Journal of Ethnopharmacology , 73 , pp 461-470, 2000).

Onion of the present invention (Allium cepa L.) is a perennial plant belonging to the genus Liliaceae, the flowers bloom in September in white, forming a stalk in the end of the flower stems between the leaves and rounded like a ball. The stalk is cylindrical, reaches 50-100cm in height, the bottom is swollen, and 2-3 leaves hang under it. The shell is divided into 6 pieces, and the split pieces are shaped like an upside down egg and spread horizontally. There are six stamens, three of which have small bumps on both sides under the operating table, with one pistil.

The varieties are divided into round shape, flat round shape, and red, yellow and white scales of the scales. Also, depending on taste, it is divided into mono onion and spicy onion. The varieties cultivated in Korea include the yellow, yellow, horticultural 1, horticultural 2, aegean and shellfish.

Harvesting is usually done when the leaves fall and have a little green color in June ~ July, and the leaves are edible before the scales grow. Onions are mainly edible, and the peculiar smell of scales is due to compounds such as propyl disulfide and allyl sulfide. It promotes the secretion of digestive juices physiologically and has an effect such as excitement, sweating and diuresis.

In addition, the scales contain minerals such as calcium and phosphate together with various vitamins to remove harmful substances in the blood. Scales are often used in salads, soups, and meat dishes, and are used as spices in various dishes. The leaves contain vitamin I 5,000 IU, vitamin C 45 mg, calcium 80 mg, magnesium 24 mg and potassium 220 mg in 100 g.

Studies on onion peels include antioxidant and synergistic effects of onion peel extracts (Song Jong-yeon et al., Korean Journal of Culinary Science, 1998), antioxidant effects of solvent extracts isolated from onion peels (Na Kyung et al., 1997). There are antioxidant effects (Jung-Soon et al., Korean Journal of Nutritionists, 1998), etc. according to the solvent extracts of onion peel and onion flesh, but none of the above documents discloses any improvement or treatment effect of onion peel on diabetes.

Therefore, the present inventors conducted a pharmacological effect of onion peel extract to find a substance having excellent effects of inhibiting rapid blood sugar rise after eating without any side effects on the living body, and excellent onion-glucosidase inhibitory activity and postprandial blood sugar rise of onion peel extract The present invention was completed by confirming the inhibitory effect.

An object of the present invention is to provide a pharmaceutical and health functional food for diabetes prevention and treatment containing onion peel extract having a significant hypoglycemic effect as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating diabetes containing onion (Allium cepa L.) peel extract having a significant hypoglycemic effect as an active ingredient.

The extract includes an extract available in a polar solvent selected from water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.

The onion includes the skin of the onion.

Hereinafter, the present invention will be described in detail.

Onion extract of the present invention can be obtained as follows.

After crushing and drying the skin of the onion of the present invention, C ₁ to C ₄ such as water, methanol, ethanol and butanol in volumes of about 2 to 15 times, preferably about 5 to 10 times the weight of the onion skin sample. A lower alcohol of or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 70 to 100% of methanol at room temperature for about 1 hour to 1 day, preferably 6 to 12 hours Extraction, cold extraction, reflux cooling extraction or ultrasonic extraction, preferably hot water extraction to separate the extract from the residue by filtration under reduced pressure, the obtained residue is about 2 to 10 times the weight of the onion peel sample at the start of extraction, preferably Is a mixed solvent having a mixing ratio of about 1 to 5 times the volume of water, C ₁ to C ₄ lower alcohols such as methanol, ethanol and butanol, or about 1: 0.1 to 1:10 thereof, preferably 70 to 100% At room temperature in ethanol for about 1 hour to 5 hours in hot water extracts, naengchim extraction, reflux extraction or ultrasonic extraction, preferably after the hydrothermal extracted the filtered under reduced pressure and concentrated to give the onions may bark extract of the present invention.

The present invention provides a pharmaceutical composition for the prevention and treatment of diabetes containing onion peel extract obtained by the above manufacturing process as an active ingredient.

In addition, the onion peel extract of the present invention has no problems such as toxicity and side effects.

The pharmaceutical composition for preventing and treating diabetes of the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.

Pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

The pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection.

Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract 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. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate and sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, 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. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, 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.

Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The extract of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

The present invention provides a health functional food containing the extract as an active ingredient exhibiting a diabetic prevention effect.

Examples of the food to which the onion peel extract can be added include various foods, powders, granules, tablets, capsules, syrups, beverages, gums, teas, vitamin complexes, and health functional foods.

It may also be added to foods or beverages for the purpose of preventing and improving diabetes. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5g, preferably 0.3 to 1g based on 100ml. .

The health functional beverage composition of the present invention is not particularly limited to other ingredients except for having the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in general beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of 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 extract 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 and 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. In addition, the extracts of the present invention may contain flesh 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 usually selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples.

However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited by the following Experimental Examples.

Reference Example  1. Preparation of experimental animals

Sprague-Dawley male rats with an average body weight of 100-120 g at 3 weeks of age were purchased from Orient Co., Ltd. and raised at the Inje University Animal Resource Center for 7 days before the experiment. It was freely ingested, temperature (23 ± 2 ℃), humidity (55 ± 10%) and contrast period (12 hours) were automatically controlled. All animal experiments were conducted according to the regulations of Inje University Animal Resource Center.

Reference Example  2. Preparation of Reagents

Yeast α-glucosidase used in this experiment was purchased from Sigma (Sigma, Louis, MO, USA), and the enzyme substrate was used as para-nitrophenyl-alpha-D-glucopyranoside. As a control, acarbose (trade name: Glucoby, Bayer-Korea), which is used clinically as a blood glucose increase inhibitor, was used (hereinafter, ab).

Reference Example  3. Statistical Processing

All experimental results were expressed as mean standard deviation (mean ± SD), and statistical tests were performed using Student's t-test and significance test was performed at p <0.05 level.

Example  1. Preparation of Onion Peel Extract

The skin of onion (purchased: Gyeongnam Changnyeong) was lyophilized and ground, and then extracted by using a magnetic stirrer for 12 hours by adding 100% methanol corresponding to 10 times the weight of onion skin sample. After filtering under reduced pressure to separate the extract and the residue, 100% methanol corresponding to 5 times the weight of the onion peel at the start of extraction was added to the obtained residue and extracted using a magnetic stirrer for 6 hours. After filtration under reduced pressure again, 100% methanol corresponding to three times the weight of onion peel at the start of extraction was added to the obtained residue, followed by extraction using a magnetic stirrer for 3 hours, followed by filtration under reduced pressure and concentration to obtain a final onion peel extract. It used as the sample of the following experiment (yield 9.73%).

Experimental Example  1. α- of onion peel extract Glucosidase  Inhibition activity measurement

The onion peel extract obtained in Example 1 was dried, dissolved in dimethyl sulfoxide at a concentration of 0.5 mg / ml to prepare a solution, and then the enzyme reaction solution containing yeast α-glucosidase. To the degree of inhibition of α-glucosidase.

Experimental results As shown in Table 1, when the 0.5mg / ㎖ concentration of onion peel extract and acarbose, it was confirmed that the inhibition of α-glucosidase activity 45.4%, 38.4%, respectively, the concentration of onion peel extract Star alphaglucosidase inhibitory activity is shown in FIG. Onion peel extract treatment group of the present invention was confirmed to show a significant hypoglycemic effect in the same concentration treatment group compared to the clinically used acarbose.

Experimental group α-glucosidase inhibition rate AL 0.50 (mg / ml) treatment 45.4% Ab 0.50 (mg / ml) treatment 38.4% * The measurement was repeated three times, and the results are expressed as average values.

Experimental Example  2. Diabetes Rat  Measurement of hypoglycemic effect of onion peel extract

Of the onion peel extract of the present invention in vivo In order to measure the hypoglycemic effect, the following experiment was performed.

That is, male rats of Reference Example 1 were injected with intraperitoneal injection of 60 mg / kg of streptozotocin (Sigma Co., USA) dissolved in 0.1 M citrate buffer (pH 4.5). Diabetes induction was confirmed.

Diabetic male rats were divided into a control group (n = 7) and a PM-administered group (n = 7), and the control group was only starch (starch, 1g / kg), and the PM-administered group was starch (1g / kg) and Onion peel extract (500mg / ㎏) was administered, the composition of the sample dosage is shown in Table 2 below. Blood samples were collected from the tail vein at 30, 60, 90, 120, 180, and 240 minutes after administration, and blood glucose was measured by a simple blood glucose meter (Accutrend, Green Cross), and the area of the blood glucose increase curve was obtained.

Experimental group Furtherance Positive control group Starch 1.0g / Kg + distilled water AL administration group Starch 1.0g / Kg + AL 0.5g / Kg + distilled water

As a result, as shown in Figure 2 and Table 3, the onion peel extract group significantly inhibited the blood glucose increase after 30 and 60 minutes after the meal compared to the control group (P <0.05), the area of the post-prandial blood glucose change curve also onion The bark extract group was significantly decreased compared to the control group (P <0.05). It was confirmed that the onion peel extract of the present invention effectively regulates blood sugar after meal in a diabetes-induced animal model.

Kinds Area of blood glucose change curve after meal (mgmin / dl) Positive control group 3,582 ± 921 ¹⁾ AL treatment group 2,353 ± 493 ^{* 1)} Mean ± SD ^* P <0.05

Experimental Example  3. Acute Toxicity Test

Acute toxicity test was performed using 6-week-old specific pathogen-free (SPF) SD rats. Two animals in each group were orally administered with onion peel extract of the present invention at a dose of 100 mg / kg. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed, and hematological and hematological examinations were performed.

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. As a result, the onion peel extract of the present invention did not show a toxic change even in rats up to 100 mg / kg, respectively, and the minimum lethal dose (LD ₅₀ ) was determined to be a safe substance of 100 mg / kg or more.

One example of the formulation of the pharmaceutical composition comprising the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail.

Formulation example  One. Powder  Produce

Onion Peel Extract 20 mg

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 Tablets

Onion Peel Extract 10 mg

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. Manufacture of capsule

Onion Peel Extract 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

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 Injectables

Onion Peel Extract 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ 12H ₂ O 26 mg

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

Formulation example  5. Liquid  Produce

Onion Peel Extract 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle. The solution is prepared by sterilization.

Formulation example  6. Manufacture of healthy food

Onion Peel Extract 1000mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B ₁ 0.13 mg

Vitamin B ₂ 0.15 mg

Vitamin B ₆ 0.5 mg

0.2 μg of vitamin B ₁₂

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

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. Manufacture of health drinks

Onion Peel Extract 100 mg

15 g of vitamin C

100 g of vitamin E (powder)

Iron lactate 19.75 g

3.5 g of zinc oxide

Nicotinamide 3.5 g

0.2 g of vitamin A

0.25 g of vitamin B ₁

0.3 g of vitamin B ₂

Water quantification

After mixing the above components according to a conventional healthy beverage production 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 sterilization and refrigerated and then 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.

As described above, the onion peel extract of the present invention not only shows excellent alpha-glucosidase inhibitory activity, but also exhibits an excellent hypoglycemic effect of suppressing a rapid increase in blood glucose concentration after meals, and the composition comprising the extract of the present invention. May be usefully used as a pharmaceutical composition and health functional food for preventing and treating diabetes.

Claims (5)

A pharmaceutical composition for preventing and treating diabetes containing onion (Allium cepa L.) bark extract as an active ingredient. The pharmaceutical composition according to claim 1, wherein the extract is an extract available in a solvent selected from water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The pharmaceutical composition according to claim 1, which comprises from 0.1 to 50% by weight of onion peel extract based on the total weight of the composition. Health functional food for the prevention and improvement of diabetes comprising onion peel extract as an active ingredient. The dietary supplement of claim 4 which is a powder, granule, tablet, capsule, syrup or beverage.

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