KR20200079206A - Composition comprising an extract of Senna obtusifolia for preventing or treating diabetes mellitus - Google Patents

Abstract

The present invention relates to a composition for preventing, treating or alleviating diabetes containing a Senna obtusifolia extract. The composition containing the Senna obtusifolia extract according to the present invention has effects of exhibiting α-glucosidase inhibitory activity, increasing the expression level of pGSK-3β, which is a factor reducing the amount of glucose in the blood, increasing intracellular glucose uptake activity into cells by improving insulin sensitivity in 3T3-L1 adipocytes having insulin resistance, and reducing fasting blood sugar in a diabetic animal model, thereby being useful as the composition for preventing, treating or alleviating diabetes.

Description

Composition comprising an extract of Senna obtusifolia for preventing or treating diabetes mellitus}

The present invention relates to a composition for preventing, treating, or improving diabetes, comprising the extract of Cassia tora.

Diabetes is a metabolic disorder caused by impaired insulin secretion and lack of action secreted by pancreatic cells, which is accompanied by overproduction of glucose, decomposition of body fat, and wasted protein and abnormally promotes glucagon secretion, causing metabolic disruption [Abrams JJ, Diabetes. 31: 903-910 (1982). In the case of diabetes, the imbalance of hormones, including insulin, is a characteristic symptom of hyperglycemia with abnormal physiological metabolic functions such as protein, lipid and electrolyte metabolism including carbohydrates [Gonuth SM, Ann. Intern. Med. 79: 812-822 (1973)], persistent hyperglycemia symptoms lead to blood circulation disorders, retinal damage, nerve cell damage, renal impairment and vascular complications [UKPDS Group,. Lancet. 352: 837-853 (1998)].

Diabetes is largely classified into two types, namely, type 1 diabetes and type 2 diabetes. Type 1 diabetes is caused by a deficiency in the secretion of insulin, a glucose-regulating hormone in the blood, mainly in young people in their 10s to 20s. It affects people of all ages. Type 2 diabetes usually develops after age 40, and accounts for the majority of diabetics. As a etiology of type 2 diabetes, both a disorder of insulin secretion in pancreatic beta cells and a defect in insulin action (insulin resistance) in target cells are observed. Insulin resistance is a major cause of type 2 diabetes in which the action of insulin is decreased in peripheral tissues [Kahn SE, Diabetologia. 46: 3-19 (2003)].

As a substance for treating type 2 diabetes, PPAR-γ activator, GLP-1 derivative, DPP-IV inhibitor, and PTP1B inhibitor have been developed as major diabetes treatment agents, but these conventional drugs show side effects due to their respective mechanisms. have. For example, the side effects include toxicity to the liver, kidneys, muscles and heart, and weight gain symptoms. In particular, when the sulfonyl urea (sulfonylurea) agent, a biguanide agent, etc., which is mainly used as an oral hypoglycemic agent, is administered, blood sugar increases rapidly after eating food, whereas insulin blood due to the administered drug My appearance is relatively slow, so I cannot solve the problem of hyperglycemia after meals and hyperinsulinemia between meals.

Accordingly, the present inventors did not cause side effects of the therapeutic agents used in the clinical practice, but while studying the composition for the treatment and prevention of diabetes that can have a strong anti-diabetic effect, as a result of processing the extract of the ginseng, alpha-glucosidase (α- glucosidase) It was confirmed that the inhibitory effect, postprandial hypoglycemic effect or fasting hypoglycemic effect was achieved, thereby completing the present invention.

Korean Registered Patent 10-1533191

An object of the present invention is to provide a pharmaceutical composition for preventing or treating diabetes, including the extract (Senna obtusifolia L.).

Another object of the present invention is to provide a health functional food composition for preventing or improving diabetes comprising the extract (Senna obtusifolia L.).

Another object of the present invention is to provide a health food composition for preventing or improving diabetes, including the extract (Senna obtusifolia L.).

In order to achieve the above object,

The present invention provides a pharmaceutical composition for preventing or treating diabetes, comprising the extract of Senna obtusifolia L.

In addition, the present invention provides a health functional food composition for preventing or improving diabetes, including the extract of Senna obtusifolia L.

Furthermore, the present invention provides a health food composition for preventing or improving diabetes including the extract of Senna obtusifolia L.

The composition comprising the extract according to the present invention shows α-glucosidase inhibitory activity, increases the expression level of pGSK-3β, a factor that reduces the amount of glucose in the blood, and 3T3 with insulin resistance -L1 improves insulin sensitivity in fat cells to increase glucose uptake into cells, and has an effect of reducing fasting blood glucose in a diabetic-induced animal model, and may be useful as a composition for preventing, treating, or improving diabetes.

1 is a graph showing α-glucosidase inhibitory activity according to the extract treatment of the present invention.
Figure 2 is a graph showing the expression level of pGSK-3β protein in diabetes-induced HepG2 cells according to the extract treatment of the present invention.
3 is a result of measuring the glucose absorption capacity of the extract of the present invention.
Figure 4 is a result of measuring the insulin concentration in the blood according to the extract treatment of the present invention in the type 2 diabetes animal model.

Hereinafter, the present invention will be described in detail.

Pharmaceutical composition for preventing or treating diabetes

The present invention provides a pharmaceutical composition for preventing or treating diabetes, comprising the extract of Senna obtusifolia L.

In the pharmaceutical composition of the present invention, the composition may further include a peanut sprout extract.

In the pharmaceutical composition of the present invention, the diabetes may be type 1 diabetes or type 2 diabetes, preferably type 2 diabetes.

In one embodiment of the present invention, the composition is mixed in a weight ratio of dried terminator powder and dried peanut sprout powder in a weight ratio of 7 to 9: 1 to 3, and the total weight of the dried terminator powder and dried peanut sprout powder. It can be prepared by extracting with an extraction solvent of 25 to 35 times, and preferably, the dried ginseng powder and dried peanut sprout powder are mixed in a weight ratio of 8:2, so that the dried ginseng powder and dried peanut sprout powder It can be prepared by extraction with an extraction solvent that reaches 30 times the total weight.

The term "extract" used in the present invention refers to a preparation that is concentrated by squeezing an extraction target with an appropriate leach solution and evaporating the leach solution, but is not limited thereto, but an extract obtained by an extraction treatment, a diluent or concentrate of the extract , It may be a dried product obtained by drying the extract, a crude product or a purified product thereof. The Cassia tora extract can be prepared using general extraction methods, separation and purification methods known in the art. The extraction method is not limited to this, but may preferably use methods such as hot water extraction, hot water extraction, cold needle extraction, reflux cooling extraction, or ultrasonic extraction.

In the pharmaceutical composition of the present invention, the extraction solvent may be water, an organic solvent or a mixed solvent thereof, and the organic solvent may be an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane Alternatively, a non-polar solvent of dichloromethane or a mixed solvent thereof can be used. In addition, preferably, water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof can be used, and more preferably 70% ethanol can be used.

In the pharmaceutical composition of the present invention, the terminator extract exhibits α-glucosidase inhibitory activity, increases the expression level of pGSK-3β, a factor that reduces the amount of glucose in the blood, and increases insulin resistance. By improving insulin sensitivity in 3T3-L1 adipocytes, glucose absorption activity into cells is increased, and there is an effect of reducing fasting blood glucose in a diabetic-induced animal model (see Experimental Examples 1 to 3 and FIGS. 1 to 4).

Extracts of the present invention can be administered in various dosage forms, oral and parenteral, during clinical administration, and when formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc., which are usually used are used. Is manufactured.

Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, etc. These solid preparations include one or more excipient extracts of at least one excipient such as starch, calcium carbonate, It is prepared by mixing sucrose, lactose, or gelatin. In addition, lubricants such as magnesium stearate talc are used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions or syrups, etc. In addition to the commonly used simple diluents, water and liquid paraffin, various excipients, such as wetting agents, sweeteners, flavoring agents, preservatives, etc. Can.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspension solutions, emulsions, lyophilized preparations, suppositories, and the like. Non-aqueous solvents, suspension solvents may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, etc. may be used.

The effective dosage amount of the extract of the present invention to the human body may vary depending on the patient's age, weight, sex, dosage form, health status and disease level, and is generally about 0.01-1000 mg/kg/day, preferably May be 0.1-500 mg/kg/day, and may be dividedly administered once to several times a day at regular time intervals according to the judgment of a doctor or pharmacist.

The pharmaceutical composition of the present invention may further include, as an active ingredient, a known diabetes treatment agent in addition to the Cassia tora extract, and may be used in combination with other treatments known for the treatment of these diseases.

Health functional food or health food composition for preventing or improving diabetes

The present invention provides a health functional food or health food composition for preventing or improving diabetes, comprising the extract of Senna obtusifolia L.

In the composition of the present invention, the composition may further include a peanut sprout extract.

In the composition of the present invention, the diabetes may be type 1 diabetes or type 2 diabetes, preferably type 2 diabetes.

In one embodiment of the present invention, the composition is mixed in a weight ratio of dried terminator powder and dried peanut sprout powder in a weight ratio of 7 to 9: 1 to 3, and the total weight of the dried terminator powder and dried peanut sprout powder. It can be prepared by extracting with an extraction solvent of 25 to 35 times, and preferably, the dried ginseng powder and dried peanut sprout powder are mixed in a weight ratio of 8:2, so that the dried ginseng powder and dried peanut sprout powder It can be prepared by extraction with an extraction solvent that reaches 30 times the total weight.

In the composition of the present invention, the extraction solvent may be water, an organic solvent, or a mixed solvent thereof, and the organic solvent may be an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane or dike. A non-polar solvent of roromethane or a mixed solvent thereof can be used. In addition, preferably, water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof can be used, and more preferably 70% ethanol can be used.

In the case of using the extract of the present invention as a health functional food and a health food composition, there is no particular limitation on the type of food. Examples of health functional foods to which the extract of the fruit of the present invention can be added may be in the form of tablets, capsules, pills or liquids, and examples of health foods include various drinks, meat, sausage, bread, candy, snacks, noodles, ice cream , Dairy products, soups, ionic beverages, beverages, alcoholic beverages, chewing gum, tea and vitamin complexes, etc., which include both health functional foods and health food compositions in the ordinary sense.

Health functional food and health food composition containing the extract according to the present invention may be added to food as it is or used with other foods or food ingredients, and may be suitably used according to a conventional method. The mixing amount of the terminator extract may be appropriately determined according to the purpose of use (for prevention or improvement). In general, the amount of the composition in the dietary supplement and health food composition can be added in 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term intake for the purpose of maintaining health or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the extract of Cassia tora may be used in an amount above the above range.

The health functional food and the health food composition of the present invention are essential ingredients in the indicated proportions, and there are no particular limitations on other ingredients other than those containing the extract of the present invention, and various flavors or natural carbohydrates, etc. are added as additional ingredients, such as ordinary drinks. It can contain. Examples of the natural carbohydrates described above include monosaccharides, such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, etc.; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (such as taumatin and stevia extract (for example, rebaudioside A, glycyrrhizine)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 health functional foods and health food composition of the present invention.

In addition to the above, the health functional food and health food composition containing the extract of the present invention of the present invention are various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.) ), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonic acid used in carbonated beverages, and the like. In addition, the health functional food and health food composition of the present invention may contain natural fruit juice and fruit flesh for the production of fruit juice beverages and vegetable beverages.

These ingredients can be used independently or in combination. The proportion of these additives is not so critical, but is generally selected from 0.1 to about 20 parts by weight per 100 parts by weight of the dietary supplement and health food composition containing the extract of the present invention.

Hereinafter, the present invention will be described in more detail by examples. It will be apparent to those skilled in the art that these examples are merely for more specifically describing the present invention, and the scope of the present invention is not limited to these examples.

<Example 1> Preparation of ginseng extract

After drying the terminus, the reflux was extracted three times for 2 hours at 50°C with 70% ethanol corresponding to 30 times (wt/v%) of the dried terminus to obtain an extract. The extract was concentrated under reduced pressure at 50°C using a rotary evaporator (Ika, China), and the concentrated solution was freeze-dried to -80°C to prepare a final ginseng extract.

<Example 2> Preparation of terminator and peanut sprout extract

Peanut sprouts were used on the 7th day of germination. The peanut sprouts were lyophilized, and the dried peanut sprout powder and the dried peanut sprout powder were mixed at a weight ratio of 8:2, and at 50°C with 70% ethanol corresponding to 30 times (wt/v%) of the total weight of the mixture. The mixture was refluxed 3 times for 2 hours to obtain an extract. The extract was concentrated under reduced pressure at 50°C using a rotary evaporator (Ika, China), and the concentrated solution was freeze-dried to -80°C to prepare final extracts and peanut sprout extract.

<Comparative Example 1> Preparation of peanut sprout extract

The extract was obtained by reflux extraction 3 times for 2 hours at 50°C with 70% ethanol corresponding to 30 times (wt/v%) of the dried peanut sprout powder. The extract was concentrated under reduced pressure at 50°C using a rotary evaporator (Ika, China), and the concentrate was freeze-dried to -80°C to prepare a final peanut sprout extract.

<Preparation example> Experiment animal

The experimental animal was a 3 week-old, type 2 diabetes model animal and was used for the experiment by adapting the BKS.Cg-m ^+/+ Lepr ^db/J mouse (db/db mouse) for 1 week. Subsequently, the normal diet control (CON), Examples 1 to 2 and Comparative Example 1 were divided into 20 and 50 mg/kg of body weight, and the fasting blood glucose of the remaining group mice except the general diet group was 200 mg/dL. From this point on, the extract was given orally for 5 weeks.

<Experimental Example 1> alpha-glucosidase inhibitory activity measurement

The extracts of Examples 1 to 2 and Comparative Example 1 were dissolved in dimethyl sulfoxide at concentrations of 10, 50 and 100 µg/ml to prepare a solution, and then the alpha-glucosidase inhibitory activity was Watanabe method [Watanabe J, et al., Biosci. Biotechnol. Biochem, 61, 177-178 (1997). The extracts of Examples 1 to 2 and Comparative Example 1 were put in an enzyme reaction solution containing yeast alpha-glucosidase to measure the degree of inhibition of alpha-glucosidase. The yeast alpha-glucosidase used in this experiment was purchased from Sigma, Louis, MO, USA, and the enzyme substrate was used as a para-nitrophenyl-alpha-D-glucopyranoside. As a control, acarbose (Acarbose, Sigma, USA) was used. The measurement was repeated three times.

As a result, as shown in Figure 1, it was confirmed that the extracts of Examples 1 to 2 and Comparative Example 1 inhibit the alpha-glucosidase activity in a concentration-dependent manner than the positive control, in particular, Example 1 or Comparative Example 1 It was confirmed that it showed excellent alpha-glucosidase inhibitory activity in the extract of Example 2 and the peanut sprout extract compared to the extract-treated group alone.

<Experiment 2> Measurement of blood glucose lowering factor

Dispense 3 ml of HepG2 cells in a 6well plate at a concentration of 2×10 ⁴ cells/well in 5% CO ₂ in DMEM-low glucose medium containing 10% FBS and 1% penicillin-streptomycin for 24 hours in an incubator at 37℃. During stabilization. After 24 hours, in order to induce the diabetic condition, the existing medium was removed, and then DMEM-high glucose-serum free medium was dispensed in 100ul increments and stabilized in a 5% CO ₂ , 37°C incubator for 24 hours. The extracts of Examples 1 to 2 and Comparative Example 1 were treated at a concentration of 250 ug/ml, respectively, and the group cultured in DMEM-low glucose (glucose) containing 10% FBS and 1% Penicillin without treating each extract Was set as a control. After incubation for 24 hours, an elution buffer (50 nM Tris-HCl, 150 mM NaCl, 1 mM EDTA, 50 mM NaF, 30 mM Na ₄ P ₂ O ₇ , 1 mM PMSF, 20 μg/mL aprotinin) was added and treated at 4° C. for 30 min. After electrophoresis of the 20 μg cell eluate on 10% Tris-HCl gel, the protein was transferred to a PVDF membrane, and 5% skim milk was pretreated on the PVDF membrane, followed by reacting the primary antibody and then treating the secondary antibody. . Protein was detected using a chemiluminescent ECL kit (Amersham Pharmacia Biotech), and the band of the expressed western blot was observed and quantified using a LAS3000® image analyzer (Fujifilm Life Science, Tokyo, apan).

As a result, as shown in FIG. 2, the expression level of pGSK-3β, a factor that decreases the amount of glucose in the blood by inducing glycogen accumulation by moving glucose into the cells, and compared with Examples 1 to 2 and comparison When the extract of Example 1 was treated, it was confirmed to be increased. In particular, it was confirmed that the expression level of pGSK-3β was significantly increased in the extract of Example 2 or the extract group of Example 2 and the peanut sprout extract compared to the extract alone treatment group. Did.

<Experimental Example 2> Measurement of glucose absorption activity

3T3-L1 adipocytes were starvated for 4 hours in serum-free DMEM medium and washed with PBS. Subsequently, after replacing with a new serum-free DMEM medium, the extracts of Examples 1 to 2 and Comparative Example 1 were treated by concentration and reacted for 30 minutes, and insulin was treated as a positive control and reacted for 10 minutes. For the measurement of glucose uptake, the amount of glucose transferred into the cell was calculated by measuring the amount of glucose contained in the medium.

As a result, as shown in FIG. 3, it was confirmed that the concentration-dependent increase of glucose uptake into adipocytes was performed. In particular, the extract of Example 1 or Comparative Example 1 compared to the treatment group of Example 2 and the peanut sprout extract of Example 2 It was confirmed that the glucose absorption activity was remarkably excellent.

<Experiment 3> Measurement of blood sugar lowering effect

In a type 2 diabetic rat model induced by a high fat diet, mice were fasted for 12 hours and sacrificed by CO ₂ inhalation. Blood was collected through posterior veins and stored in a heparin tube. Then, the blood was centrifuged (10,000 × g, 4°C) for 10 minutes, and the supernatant was used in this experiment. Fasting blood glucose was measured using a blood glucose meter (ACCU-CHEK, Roche Diagnostics, Mannheim, Germany) through the tail vein of a fasted mouse for 12 hours.

As a result, as shown in FIG. 4, blood glucose increased significantly in the diabetic model compared to the normal group, and as a result of treating the extracts of Examples 1 to 2 and Comparative Example 1 in an animal model inducing diabetes with a high-fat diet, blood glucose This was confirmed to be reduced, and in particular, it was confirmed that the blood sugar was significantly reduced in Example 2 and the peanut sprout extract treatment group.

So far, the present invention has been focused on the preferred embodiments. Those skilled in the art to which the present invention pertains will understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered in terms of explanation, not limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent range should be interpreted as being included in the present invention.

Claims (11)

Pharmaceutical composition for preventing or treating diabetes, comprising extract of Senna obtusifolia L. According to claim 1,
The pharmaceutical composition for preventing or treating diabetes, characterized in that it further comprises a peanut sprout extract. According to claim 1,
The extract is a pharmaceutical composition for preventing or treating diabetes, characterized in that extracted with water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. Health functional food composition for preventing or improving diabetes, comprising extract of Senna obtusifolia L. According to claim 4,
The health functional food composition is a health functional food composition for preventing or improving diabetes, further comprising a peanut sprout extract. According to claim 4,
The extract is water, C 1 to C 4 alcohol or a health functional food composition for preventing or improving diabetes, characterized in that extracted with a mixed solvent thereof. According to claim 4,
The health functional food is a health functional food composition for preventing or improving diabetes, characterized in that the food in the form of tablets, capsules, pills or liquids. A health food composition for preventing or improving diabetes, comprising extract of Senna obtusifolia L. The method of claim 8,
The health food composition is a health food composition for preventing or improving diabetes, further comprising a peanut sprout extract. The method of claim 8,
The extract is a health food composition for preventing or improving diabetes, characterized in that extracted with water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. The method of claim 8,
The health food is prevented or improved diabetes, characterized in that selected from various drinks, meat, sausage, bread, candy, snacks, noodles, ice cream, dairy products, soups, ionic beverages, beverages, alcoholic beverages, chewing gum, tea and vitamin complexes Dragon healthy food composition.

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