KR100551464B1 - Composition comprising an extract of Saururus chinensis BAILL. for preventing and treating diabetes mellitus - Google Patents

Abstract

The present invention relates to a composition containing a tritical herb leaf extract having a significant hypoglycemic effect as an active ingredient, the tritical herb leaf extract of the present invention not only shows excellent α-glucosidase inhibitory activity but also slows the digestion rate of carbohydrates after meals. Since it suppresses a rapid rise in blood glucose concentration, the composition comprising the same can be usefully used as a pharmaceutical and dietary supplement for the prevention and treatment of diabetes.

300 seconds, α-glucosidase, hypoglycemic, diabetes, drug

Description

Composition comprising an extract of Saururus chinensis BAILL. for preventing and treating diabetes mellitus}             

1 is a diagram showing the change in postprandial blood glucose levels when administration of starch leaf extract (500 mg / kg) with starch (1 g / kg) and starch (1 g / kg) in diabetic rats.

The present invention relates to a composition for the prevention and treatment of diabetes, comprising as an active ingredient three hundred seconds leaf extract having a significant hypoglycemic effect.

Diabetes is defined as a metabolic disorder caused by insulin secretion and a lack of action of insulin secreted by pancreatic cells and involves excessive production of glucose, breakdown of body fat and waste of protein, and abnormal glands of glucagon, resulting in metabolic disruption. (Abrams, JJ, Ginsberg, H. et al., Diabetes, 31 , pp 903-910, 1982).

Diabetes mellitus is characterized by two types, type 1 diabetes mellitus, which is caused by a lack of secretion of insulin, a glucose-regulating hormone in the blood, mainly in young people in their 10s to 20s. It is also called juvenile diabetes because it develops. Type 2 diabetes mellitus mainly occurs after the age of 40, and occupies most of the diabetic patients in Korea. Unlike type 1, 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. As a etiology of type 2 diabetes, both insulin secretion in pancreatic beta cells and defects in insulin action (insulin resistance) in target cells are observed.

The most important goal in the treatment of diabetes is to control blood glucose levels as close to normal as possible, and postprandial blood sugar control, together with fasting blood glucose, is important for the prevention and treatment of diabetic symptoms and complications (Jenkins, DJA, Wolever et al., Starchy foods and glycemic index.Diabetes Care , 11 , pp149-159, 1988; Menendez, CM, Stoecker, BJ, The role of diet in improving glycemic control in Nutrition and Diabetes.Javanovic, L. and Peterson, CM (ed.) , Alan R. Liss Inc., pp 15-36, 1995), treatments include pharmacotherapy, diet and exercise therapy.

Currently, oral hypoglycemic agents used in type 1 and type 2 diabetes patients include α-glucosidase inhibitors, sulfonylureas, and biguanides, and α-glucose Sidase inhibitors have a therapeutic effect on diabetes by delaying the digestion and absorption of carbohydrates in the ingested diet, thereby reducing the elevation of postprandial blood sugar and blood insulin. α-glucosidase inhibitors promote the secretion of glucagon-like peptide-1 in the small intestine that promotes insulin secretion and suppresses glucagon secretion without causing hyperinsulinemia or hypoglycemia Have advantages (Mooradian, AD, Thurman, JE, Drugs, 57 , pp 19-29, 1999; Baron, AD, Diabetes Research and Clinical Practice , 40 , ppS54-S55, 1998).

Currently used in the clinical practice include acarbose (acarbose), bogilibose (voglibose) and miglitol (miglitol), but long-term use of α-glycosidase inhibitors, side effects such as abdominal bloating, vomiting diarrhea in some patients And its use may be limited (Hanefeld, M., Journal of Diabetes and its Complications, 12 , pp228-237, 1998).

Saururus chinensis BAILL. Of the present invention is a perennial herb belonging to the Saururaceae family, which inhabits waterside or wetlands in Ulleungdo and northwestern Jeju, and is distributed in Japan, China, and the Philippines. It is 60-90cm in height and root length is white and stretches sideways in the mud. It is called three hundred seconds because 2-3 leaves, flowers and roots are white when the flowers bloom (Go Kyung, Je Ri, Korean wild plants, Iljinsa, p91, 2003). Outpost contains essential oils, the main components of which are quercetin, quercitrin, isoquercitrin, rutin and water-soluble tannins, detoxification, swelling, urinary deficiency, hepatitis , Jaundice, etc. (Kim Jae-gil, natural product metabolism, Namsandang, p174, 1984). Quiercetin and quercitrin, the main components of 300 seconds, are a type of flavonoid belonging to the flavonol family and are known to be found in many fruits and vegetables (Formica, J. et al., Food and Chemical Toxicology ., 33 , pp 1061-1080, 1995).

In addition, the identification and anti-cancer mechanisms of anti-cancer active substances derived from trichophytium (Ham Jong-cheon, Ph.D. thesis, Graduate School of Seoul National University, 2001) and the isolation and identification of components with hepatocellular protective activity from trichophytium (Kwon Soo-hyun, MS) Thesis, the Graduate School of Seoul National University, 1996) and the like, but none of the above literature has been taught about the improvement and treatment effect of the blood glucose control-related diabetes symptoms of three hundred seconds leaf extract.

The present inventors have tested the pharmacological effect of the extract of three hundred seconds leaf extract to provide a substance with excellent postprandial glycemic inhibitory effect without any side effects on the living body, confirming the excellent α-glucosidase inhibitory activity and postprandial hypoglycemic effect of three hundred seconds leaf extract By this, the present invention was completed.

An object of the present invention is to provide a pharmaceutical and health functional food for the prevention and treatment of diabetes containing three hundred seconds leaf 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 300 seconds ( Saururus chinensis BAILL.) Leaf extract having a significant hypoglycemic effect as an active ingredient.

The extract includes water extracted from C ₁ to C ₄ lower alcohols such as water, ethanol, methanol, or a mixed solvent thereof.

Hereinafter, the present invention will be described in detail.

The triticale leaf extract of the present invention can be obtained as follows.

Three hundred seconds leaf of the present invention is purchased, lyophilized and _ground , and then the volume of water up to about 2 to 15 times, preferably about 5 to 10 times the weight of the three hundred seconds leaf sample, and C ₁ to Polar solvent of C ₄ lower alcohol or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 70 to 100% methanol at room temperature for about 1 hour to 1 day, preferably 6 Extraction method using a magnetic stirrer, extraction with hot water, cold needle extraction, reflux cooling extraction or ultrasonic extraction for a period of time to 12 hours, preferably extraction with a magnetic stirrer to separate the extract liquid and the residue by filtration under reduced pressure Next, the obtained residue has a volume of water of about 2 to 10 times, preferably about 3 to 5 times, the weight of the 300 sec leaf sample at the start of extraction, and C ₁ to C such as methanol, ethanol, butanol, and the like. ₄ is a polar solvent of a lower alcohol of ₄ or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably hot water extraction and cold extraction for about 1 to 5 hours at room temperature with 70 to 100% methanol By using an extraction method such as reflux cooling extraction or ultrasonic extraction, preferably hot water extraction, followed by filtration and concentration under reduced pressure can obtain a triticale leaf extract.

In addition, conventional fractionation processes can also be carried out (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis, 3rd Ed. , Pp 6-7, 1998).

The present invention provides a pharmaceutical composition for the prevention and treatment of diabetes mellitus containing three hundred seconds leaf extract obtained by the above manufacturing process as an active ingredient.

As a result of measuring the α-glucosidase inhibitory activity of the three hundred sec leaf extract obtained by the above method, it showed a significant α-glucosidase inhibitory activity compared to the control group acarbose administration group, in vivo using diabetic rats ( in vivo ) Also showed significant hypoglycemic effect.

In addition, the three hundred seconds is a drug that has been used for a long time or edible herbal extracts of the present invention extracted therefrom also have 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.

Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in any 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 the solid preparations may include at least one excipient such as starch, calcium carbonate, 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 desired effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 100 mg / kg. 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 comprising the extract and a food acceptable food supplement additive exhibiting a diabetes prevention effect. Examples of foods to which the triticale leaf extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It may also be added to foods or beverages for the purpose of preventing 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 containing the extract as an essential ingredient in the indicated proportions, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. 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.

Example 1. Preparation of Triticale Leaf Extract

After crushing the leaves of three hundred seconds (purchased by Kwang Myung Co., Ltd.), the leaves were pulverized and extracted with a magnetic stirrer for 12 hours by adding 100% methanol corresponding to 10 times the weight of the three hundred seconds leaf sample. After filtration under reduced pressure, the extract was separated from the residue, and 100% methanol corresponding to 5 times the weight of the sample of 300 seconds leaf at the beginning 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 the sample of 300 sec leaves at the beginning 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 extract of 300 sec. The yield was 17.6%.

Experimental Example 1. Determination of α-glucosidase inhibitory activity of three hundred vine leaf extract

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 clinically used as an antihyperglycemic agent, was used. After drying the methanol extract of three hundred seconds leaf obtained in Example 1, dissolved in dimethyl sulfoxide at a concentration of 0.5 mg / ㎖ to prepare a solution, and then the enzyme reaction solution containing yeast (alpha)-glucosidase To the degree of inhibition of α-glucosidase.

As a result, it was confirmed that at 300 mg / ㎖ trifoliate leaf methanol extract and acarbose significantly inhibited α-glucosidase by 49.8% and 40.2%, respectively (see Table 1 below).

Concentration (mg / ml) Triticale Leaf Methanol Extract Akabos 0.50 49.8% 40.2%

* The measurement was repeated three times, and the results are expressed as average values.

Experimental Example 2. Determination of hypoglycemic effect of triticale leaf extract in diabetic rats

In vivo in vitro three hundred seconds leaf extract showed excellent α- glucosidase inhibiting activity in the (In vitro) test (in vivo) In order to measure the hypoglycemic effect, the following experiment was performed.

That is, 65 mg / kg of streptozotocin (Sigma Co., USA) dissolved in 0.1M citrate buffer (pH 4.5) in Sprague-Dawley male rats having an average weight of 250-280 g. Was injected into the abdominal cavity to induce diabetes, and after one week confirmed the induction of diabetes. Sprague-Dawley male rats with an average body weight of 111.5 ± 12.7 g were divided into a control group and a three hundred leaf extract group, and the control group had only starch (starch, 1 g / kg), and a three hundred second leaf extract group had a starch (1 g / kg) and the above example. Three hundred sec leaf extract (500 mg / kg) obtained in 1 was dissolved and administered in physiological saline, and the composition of the sample dosage solution is shown in Table 2 below. At 30, 60, 90, 120, 180, and 240 minutes after administration, blood was collected from the tail vein, and blood glucose was measured by a simple blood glucose meter (Accutrend, Green Cross), and the area of the blood glucose increase curve was determined.

The experimental results showed that the control group of the 300 sec leaf extract significantly inhibited the increase in blood glucose levels at 60 and 90 minutes after the meal compared to the control group ( P <0.05). ( P <0.05). As a result, it was confirmed that the post-prandial glycemic control effect of the extract of the three hundred herb leaf in diabetic animals (see Fig. 1 and Table 3).

Composition of Sample Dose for Experiments on Efficacy of Glucose Inhibition in Rats ingredient Control Triticale leaf administration group Soluble starch 1.0 g 1.0 g Triticale Leaf Extract - 0.5 g Distilled water 7.5 ml 7.5 ml

Differences in the Blood Glucose Growth Curves of Oral Trichophyte Leaf Extract with Starch Kinds Area of blood glucose change curve after meal (mg · min / ㎗) Starch 12,348 ± 1,110 ¹⁾ Starch + triticale leaf 8,898 ± 838

¹⁾ Mean ± SD

Experimental Example 3. Acute Toxicity Test

Acute toxicity testing was performed using 6-week-old specific pathogen-free (SPF) SD rats. Two animals of each group were administered orally with a dose of 100 mg / kg of the triticale leaf extract of the present invention. 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 visually observe abnormalities in organs and thoracic organs.

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 triticale leaf 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 1 Preparation of Powder

Triticale Leaf Extract Powder 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 Tablet

Triticale Leaf Extract Powder 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 Preparation of Capsule

Triticale Leaf Extract Powder 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 Injection

Triticale Leaf Extract Powder 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _{4 12} H 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 Preparation of Liquid

Triticale Leaf Extract Powder 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.

Formulation Example 6 Preparation of Healthy Food

300mg Leaf Extract Powder 1000mg

Vitamin Mixture

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

Folate 50 ㎍

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

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

Formulation Example 7 Preparation of Healthy Drink

300mg Leaf Extract Powder 100mg

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 in accordance with a conventional healthy beverage production method, and 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 then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is a composition suitable for a preferred 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 triticale leaf extract of the present invention not only exhibits an excellent α-glucosidase inhibitory activity, but also slows the digestion rate of carbohydrates after meals and thus suppresses a sharp increase in blood glucose levels, and thus the composition comprising the same may be used to prevent diabetes and It can be usefully used as a medicine or health food for treatment.

Claims (5)

A pharmaceutical composition for preventing and treating diabetes, comprising as an active ingredient a extract of Saururus chinensis BAILL. Having a hypoglycemic effect. The pharmaceutical composition according to claim 1, wherein the extract is water and an extract available for C ₁ to C ₄ lower alcohols such as methanol, ethanol, butanol, and the like, or a mixed solvent thereof. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises 0.1 to 50% by weight, based on the total weight of the composition. A dietary supplement comprising three hundred vine leaf extracts and food-acceptable food supplements that have an effect of preventing and improving diabetes. The health functional food of Claim 4 which is a health drink.

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