KR20190035972A - Composition comprising an extract of Elaeagnus umbellata for preventing and treating diabetes mellitus - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing and treating diabetes containing an extract of Elaeagnus umbellata as an active component and various uses related to the same. Using the extract of Elaeagnus umbellata of the present invention prompts an α-glucosidase inhibitory effect, a postprandial blood glucose lowering effect or a fasting blood glucose lowering effect, thereby being effective for preventing and treating diabetes. In addition, since the extract of Elaeagnus umbellata does not occur side effects of existing clinically used diabetic drugs, but has an anti-diabetic effect in accordance with the same, it is possible to be usefully used in related pharmaceutical and food fields.

Description

The present invention relates to a composition for prevention and treatment of diabetes mellitus,

The present invention relates to a pharmaceutical composition for preventing and treating diabetes mellitus comprising an extract of native wheat liquor as an active ingredient and various uses related thereto.

Diabetes mellitus is a metabolic disorder induced by insulin secretion and insufficient secretion from pancreatic cells, resulting in overproduction of glucose, breakdown of body fat, waste of protein, abnormal hyperglycemia of glucagon, [Abrams JJ, Diabetes. 31: 903-910 (1982)). Diabetes mellitus is characterized by a hormonal imbalance including insulin, which is characteristic of hyperglycemia due to abnormal regulation of physiological metabolism such as carbohydrate, protein, lipid and electrolytic metabolism [Gonuth SM, Ann. Intern. Med. 79: 812-822 (1973)], persistence of these hyperglycemic symptoms leads to blood circulation disorders, retinal injury, neuronal cell damage, renal dysfunction and vascular complications [UKPDS Group,. Lancet. 352: 837-853 (1998).

There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is caused by a deficiency in the secretion of insulin, the glucose-regulating hormone in the blood, ≪ / RTI > Type 2 diabetes occurs mainly after the age of 40 and accounts for the majority of diabetic patients. As a cause of type 2 diabetes, insulin secretion in pancreatic beta cells and insulin action defects in target cells (insulin resistance) are all observed. Insulin resistance is a major cause of type 2 diabetes in a state where insulin action is impaired in peripheral tissues (Kahn SE, Diabetologia. 46: 3-19 (2003)).

The most important goal in the treatment of diabetes is to regulate blood sugar levels as close to normal as possible. Therapeutic methods include pharmacotherapy, diet and exercise therapy. Currently, oral hypoglycemic agents used in diabetic patients are α-glucosidase inhibitors, sulfonylurea agents and biguanide agents, and α-glucosidase inhibitors are used in the diet And the reduction of postprandial blood glucose and blood insulin elevation, thereby exhibiting the therapeutic effect of diabetes mellitus. The α-glucosidase inhibitor has the advantage of promoting secretion in the small intestine of glucagon-like peptide-1, which promotes insulin secretion and inhibits glucagon secretion without causing hyperinsulinemia or hypoglycemia [Mooradian AD, Drugs. 57: 19-29 (1999); Baron AD, Diabetes Research and Clinical Practice. 40: S54-S55 (1998).

Acarbose, voglibose and miglitol are currently used in clinical practice. However, when a long-acting α-glucosidase inhibitor is used in some patients, abdominal bloating, vomiting or diarrhea And may limit its use [Hanefeld M, Journal of Diabetes and its Complications. 12: 228-237 (1998)).

Elaeagnus plants are distributed in about 45 species around the world. In Korea, E. umbellata Thunb. (Autumn olive), a deciduous broadleaved tree, and E. multiflora ) Are common.

The native borealum is a deciduous broad-leaved shrub belonging to Elaeagnusae (Elaeagnaceae). It is widely distributed in the Gaya River area in Korea and is widely distributed in private areas. It is known as borealis. It grows well in the mountains and rivers of the country and grows in the barren land. In October ~ November, the fruit is opened like a bunch of grapes and ripens in red color. Fruits are 1 cm long, spherical, with a slightly reddish taste and sweetness. Leaves are alternate phyllotaxis, oval, and the upper part is dark green [Kim MJ, J Korean Soc Food Sci Nutr. 45: 828-834 (2016)].

It is said to be effective in treating cough, sputum, asthma, diarrhea and hemorrhage, and it is said to be effective in treating the fruit of the garden borealum as a tree half-summer. Diarrhea, bleeding, indigestion, and physiological impurities are known to be effective. The indigenous borage fruit is used as a herbal medicine, but the fruit is small in size and has a sweet taste and a pungent taste.

Accordingly, the present inventors have studied a composition for the treatment and prevention of diabetes which can exhibit a potent antidiabetic effect without causing adverse side effects of conventional therapeutic agents, In vivo, the present inventors have confirmed that α-glucosidase inhibitory effect, postprandial blood glucose lowering effect or fasting blood glucose lowering effect are obtained as a result of the treatment, and thus the present invention has been completed.

It is an object of the present invention to provide a pharmaceutical composition for preventing and treating diabetes comprising an extract of native wheat liquor as an active ingredient.

It is also an object of the present invention to provide a health functional food for diabetes prevention and improvement comprising an extract of native wheat liquor as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating diabetes comprising an extract of native whey extract as an active ingredient.

In addition, the present invention provides a health functional food for prevention and improvement of diabetes comprising an extract of native wheat liquor as an active ingredient.

When the native lysine extract of the present invention is used, it has an alpha-glucosidase inhibitory effect, postprandial blood glucose lowering effect or fasting blood glucose lowering effect and is effective for diabetes prevention and treatment. In addition, the anti-diabetic effect similar to that of a conventional diabetic drug used in clinical practice does not occur and can be usefully used in related pharmaceutical and food fields.

FIG. 1 is a graph showing the results of postprandial blood glucose lowering after treatment of control, barley, and acarbose groups in normal mice.

The present invention provides a pharmaceutical composition for the prevention and treatment of diabetes comprising an extract of native wheat liquor as an active ingredient.

The present invention also relates to a method of treating diabetic rheumatoid arthritis, which comprises administering an effective amount of an anti-diabetic agent in an amount of 0.01 to 3% by weight, preferably 0.01 to 1% by weight based on the total weight of the composition, Is not limited to this.

The native wheat liquor extract is extracted from at least one selected from the group consisting of fruit, leaves, roots, stems, flowers, husks and branches, and is not limited thereto, so long as it is a fruit or an antidiabetic effect.

The native wheat germ extract is extracted with a solvent selected from the group consisting of water, alcohol, organic solvent, and a mixture thereof, and is not limited thereto, for the purpose of effectively extracting ethanol (alcohol) or native wheat bran .

The native lysate extract may exhibit an alpha-glucosidase inhibitory effect, a postprandial blood glucose lowering effect or an fasting blood glucose lowering effect, and the diabetes is not limited to type 2 diabetes.

The pharmaceutical composition of the present invention may further include an adjuvant in addition to the native water extract. Such adjuvants may be used without limitation as long as they are known in the art, but may include, for example, Freund's complete or incomplete adjuvant to increase its immunity.

The pharmaceutical composition according to the present invention can be prepared by incorporating the active ingredient into a pharmaceutically acceptable carrier. Here, the pharmaceutically acceptable carrier includes carriers, excipients and diluents commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers for use in the pharmaceutical compositions of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, Calcium phosphate, calcium silicate, cellulose, methylcellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The pharmaceutical composition of the present invention can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols or the like, oral preparations, suppositories or sterilized injection solutions according to a conventional method .

In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants and the like which are usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations may contain at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin And the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, and syrups. In addition to commonly used diluents such as water and liquid paraffin, various excipients such as wetting agents, sweetening agents, fragrances and preservatives . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Propellants, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used. As the base of suppositories, witepsol, tween 61, cacao paper, laurin, and glycerogelatin can be used.

The pharmaceutical composition according to the present invention can be administered to the individual by various routes. All modes of administration may be expected, for example, by oral, intravenous, intramuscular, subcutaneous, intraperitoneal injection.

The dosage of the pharmaceutical composition according to the present invention is selected in consideration of the age, weight, sex, physical condition, etc. of the individual. It is obvious that the concentration of the native lysine water extract contained in the pharmaceutical composition may be variously selected depending on the subject, preferably 0.01 to 5,000 占 퐂 / ml in the pharmaceutical composition. If the concentration is less than 0.01 μg / ml, the pharmaceutical activity may not be exhibited. If the concentration is more than 5,000 μg / ml, it may be toxic to the human body.

The pharmaceutical composition for preventing or treating diabetes may be formulated into various oral or parenteral administration forms.

Examples of formulations for oral administration include tablets, pills, hard, soft capsules, liquids, suspensions, emulsions, syrups, granules and the like. These formulations may contain, in addition to the active ingredient, a diluent such as lactose, dextrose, (For example, silica, talc, stearic acid and magnesium or calcium salts thereof and / or polyethylene glycol), in addition to the active ingredient (s). The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, optionally mixed with starch, agar, alginic acid Or a disintegrating or boiling mixture such as its sodium salt and / or an absorbent, a colorant, a flavoring agent and a sweetening agent. The formulations may be prepared by conventional mixing, granulating or coating methods.

Representative examples of formulations for parenteral administration include injectable preparations, and water, Ringer's solution, isotonic saline or suspensions may be mentioned as a solvent for the injectable preparation. The sterile, fixed oils of the injectable preparations may be used as a solvent or suspending medium, and any non-irritating fixed oils, including mono-, di-glycerides, may be used for this purpose.

The injectable preparation may be a fatty acid such as oleic acid.

In addition, the present invention provides a health functional food for prevention and improvement of diabetes comprising an extract of native wheat liquor as an active ingredient.

The health functional food for preventing or ameliorating diabetes, which contains the native native lime extract of the present invention as an active ingredient, can be used for lowering blood glucose, and contains 0.0001 to 10% by weight of native lycopene extract on the basis of the total weight of the health functional food .

The health functional food may be in the form of a capsule, tablet, powder, granule, liquid, ring, flaky, paste, syrup, gel, jelly and jute for the purpose of supplementing nutrients that may be lacking in daily eating or supplementing functional raw materials useful in the human body And is easily manufactured and operated once.

In addition, the health functional food may contain one or more selected from the group consisting of glucose, citric acid, liquid oligosaccharide, corn syrup, soybean lecithin, butter, vegetable hardening oil, skim milk, sugar, margarine, salt, starch, wheat flour, And can be prepared by using commonly used components such as sodium bicarbonate and sugar ester.

The present invention will be described in more detail with reference to the following examples. However, the following examples are only for the purpose of illustrating the present invention, and thus the present invention is not limited thereto.

Example 1. Preparation of indigenous fruit juice extract

In this experiment, the fruit of native wheat liquor (purchased from Kyongnam Hapcheon) was freeze-dried and ground, and 100% alcohol equivalent to 10 times the weight of the native wheat liquor was added and extracted for 12 hours using a magnetic stirrer. The extract was separated by filtration under reduced pressure (Wattmann, USA), and the extract and the residue were separated. The residue was then extracted with a magnetic stirrer for 5 hours. The filtrate was filtered again under reduced pressure, and then 100% alcohol corresponding to 15 times was added to the obtained residue. The mixture was extracted with a magnetic stirrer for 3 hours and then filtered under reduced pressure. The filtrate was collected and concentrated under reduced pressure at 37 using a vacuum rotary evaporator. , And the extract was stored at -20. The extraction yield was 59.3%.

Experimental Example 1. Measurement of alpha-glucosidase inhibitory activity of native fruit extract

The extract of native wheat bran obtained in Example 1 was dissolved in dimethyl sulfoxide at a concentration of 0.5 mg / mL to prepare a solution. The alpha-glucosidase inhibitory activity was measured by Watanabe method [Watanabe J, et al., Biosci . Biotechnol. Biochem, 61, 177-178 (1997)). The inhibitory effect of alpha - glucosidase was measured by adding the native fruit extract to an enzyme reaction solution containing yeast alpha - glucosidase. The yeast alpha-glucosidase used in this experiment was purchased from Sigma, Louis, MO, USA. The enzyme substrate used was para-nitrophenyl-alpha-D-glucopyranoside, As a control, acarbose (trade name: GlucoBai, Bayer-Korea), which is clinically used as a blood sugar elevation inhibitor, was used. The measurements were repeated three times and the results were expressed as mean ± standard error. The results are shown in Table 1.

As shown in Table 1, it was confirmed that alpha-glucosidase activity was inhibited to 45.8. + -. 1.8% and 42.1. + -. 1.1%, respectively, when the native fruit extract and acarbose were treated at a concentration of 0.5 mg / mL. Therefore, the in vitro test showed that the extract of native wheat liquor showed superior alpha-glucosidase inhibitory activity than the positive control group of acarbose.

Concentration (mg / ml) Indigenous fruit extract Acabos 0.50 45.8 ± 1.8% 42.1 ± 1.1%

Experimental Example 2. Measurement of postprandial blood glucose lowering effect of fruit juice extract of native wheat bran in normal mice

In order to measure the in vivo blood glucose lowering effect of the fruit juice extract of native barley which showed excellent inhibitory activity of alpha-glucosidase in in vitro experiments, the following experiment was conducted.

More specifically, 5-week-old male C57BL / 6J (n = 18) was purchased, and water and chow were freely taken until the body weight reached 25-30 g. Humidity (55 ± 10%) and light intensity (12 hours) were automatically adjusted. All animal experiments were conducted according to the regulations of the Animal Resource Center of Inje University.

In order to measure postprandial blood glucose lowering effect of the native fruit juice extract of the present invention, mice (25-30 g) were divided into control (n = 6), barley (n = 6) and acarbose I divided it. (1 g / ㎏) and maltose (1 g / ㎏) were used as the control group, maltose (1 g / ㎏) and barley fruit extract (500 ㎎ / Acarbose (50 mg / kg) was administered. Serum was collected from the tail vein before administration (0 min) and after administration (30 min, 60 min, 90 min and 120 min). Blood glucose was measured by enzyme assay using glucose assay kit (Asan Pharma). All results were expressed as mean ± standard error. The significance test between each group was performed using one-way ANOVA and the Tukey's test was used as post test (p <0.05). The results are shown in FIG. 1 and Table 2.

As shown in FIG. 1, the increase in postprandial blood glucose of the barley group was significantly lower than that of the control group at 30 minutes (p <0.01) and 60 minutes (p <0.05). In addition, there was no significant difference in postprandial blood glucose increase compared to the positive control group, Acabos.

In addition, as shown in Table 2, the area of the postprandial blood glucose change curve was examined, and it was confirmed that the barley group was significantly decreased (p <0.01) compared with the control group. In addition, it was confirmed that there was no significant difference when compared with the positive control group of acarbose.

Therefore, it was confirmed that the extract of native wheat liquor according to the present invention had no significant difference compared with acarbose which was used in the prior art, and that the postprandial blood glucose control effect of the diabetic animal model was excellent.

group The area of postprandial blood glucose change curve (㎎min / dL) Control group 5756.3 ± 700.1 ^b Barley 3432.6 ± 395.1 ^a Acabos County 2554.5 ± 252.6 ^a Significance p <0.01

Experimental Example 3. Determination of long-term blood glucose control effect of native fruit juice extract in diabetic animal model

Five-week-old male C57BL / Ks-db / db mice (type 2 diabetic animal model) were divided into four groups according to the nude method after 1 week of adaptation period. The specific dietary composition is shown in Table 3, and the control group (n = 7) was given the AIN-93G diet and the barley water group (low concentration group: n = 7; high concentration group: n = 7) Diets containing low concentrations (0.4%) and high concentrations (0.8%) were given for 7 weeks in the positive control group (n = 7) with acarbose (0.04%). Animals fed the diet for 7 weeks were sacrificed by cardiac collection after fasting for 12 hours. Serum glucose concentration (blood glucose) was measured by enzyme assay using glucose assay kit (Asan Pharma). The blood glycosylated hemoglobin concentration was measured by chromatography using IJ-A-One (Infovia). All results were expressed as mean ± standard error. The significance test between each group was performed using one-way ANOVA and the Tukey's test was used as post test (p <0.05). Body weight and dietary intake of each group are shown in Table 4 below. In addition, serum glucose and blood glycosylated hemoglobin concentrations in diabetic rats for each group are shown in Table 5 below.

As shown in Table 4, the body weight and the dietary intake of the control group, the 0.4% barley group, the 0.8% barley group and the acarbose group were not significantly different from each other.

As shown in Table 5, serum glucose (blood glucose) of diabetic rats was found to be 0.4% barley (365.8 ± 16.6 mg / dL) and 0.8% barley (346.6 ± 18.9 mg / dL) was significantly lower than that of the control group (446.3 ± 17.6 mg / dL) (p <0.05). In addition, the 0.4% barley and 0.8% barley groups were not significantly different from the acarbose group (315.4 ± 13.0 mg / dL).

In addition, blood glycosylated hemoglobin concentration in each group was found to be higher than that of the control group (8.0 ± 0.2%) in 0.4% barley group (7.2 ± 0.2%) and 0.8% barley group (P < 0.05). In addition, the 0.4% barley and 0.8% barley groups were not significantly different from the blood glycosylated hemoglobin concentration (6.8 ± 0.2%) of the acarbose group.

Therefore, it was confirmed that the long-term intake of the native barley fruit extract in db / db mouse of the type 2 diabetic animal model effectively reduced fasting blood glucose.

According to the Experimental Example, it was confirmed that the native fruit juice extract of the present invention inhibits alpha-glucosidase activity, and has a postprandial blood glucose lowering effect and fasting blood glucose lowering effect, thereby effectively preventing and treating diabetes.

ingredient group (%) Control group 0.4% barley 0.8% barley Acabos County Casein 20.00 19.96 19.91 20.00 Corn starch 39.75 39.49 39.24 39.71 Honey corn starch 13.20 13.20 13.20 13.20 Sucrose 10.00 10.00 10.00 10.00 alpha -cellulose 5.00 4.91 4.83 5.00 Soybean oil 7.00 6.99 6.97 7.00 Vitamin mixture ¹⁾ 1.00 1.00 1.00 1.00 Mineral mixture ²⁾ 3.50 3.50 3.50 3.50 L-cystine 0.30 0.30 0.30 0.30 Choline 0.25 0.25 0.25 0.25 4-butylhydroquinone ³⁾ 0.0014 0.0014 0.0014 0.0014 Lime extract - 0.40 0.80 - Acabos - - - 0.04 ¹⁾ AIN-93 vitamin mixture
²⁾ AIN-93 mineral mixture
³⁾ Antioxidant, 0.01 g / 50 g lipids

group Control group 0.4% barley 0.8% barley Acabos County Weight (g) 41.9 ± 1.1 ^ns 40.0 ± 1.3 39.1 ± 1.3 39.3 ± 1.1 Dietary intake (g / d) 4.2 ± 0.2 ^ns 4.0 ± 0.1 3.9 ± 0.1 3.9 ± 0.1

group Control group 0.4% barley 0.8% barley Acabos County Serum glucose
(mg / dL) 446.3 ± 17.6 ^b 365.8 ± 16.6 ^a 346.6 ± 18.9 ^a 315.4 ± 13.0 ^a Blood glycosylated hemoglobin
(%) 8.0 ± 0.2 ^b 7.2 ± 0.2 ^a 7.0 ± 0.2 ^a 6.8 ± 0.2 ^a Significance p <0.05

Claims (7)

A pharmaceutical composition for the prevention and treatment of diabetes comprising an extract of Elaeagnus umbellata Thunberg as an active ingredient. The method according to claim 1,
The pharmaceutical composition for the prevention and treatment of diabetes according to any one of claims 1 to 3, wherein the native aqueous extract is contained in an amount of 0.01 to 3% by weight based on the total weight of the composition. The method according to claim 1,
Wherein the native extract is extracted from at least one selected from the group consisting of fruit, leaves, roots, stems, flowers, husks and branches. The method according to claim 1,
Wherein the native extract is extracted with a solvent selected from the group consisting of water, alcohol, organic solvent, and mixtures thereof. The method according to claim 1,
The pharmaceutical composition for preventing and treating diabetes according to claim 1, wherein the native lysine extract has an alpha-glucosidase inhibitory effect, postprandial blood glucose lowering effect or fasting blood glucose lowering effect. The method according to claim 1,
Wherein the diabetes is type 2 diabetes. A health functional food composition for preventing or ameliorating diabetes, which comprises native liver liquor extract as an active ingredient.

Images