KR20090106700A - Pharmaceutical composition comprising extracts of Chrysanthemi Flos for treating and preventing diabetes and diabetic complications - Google Patents

Abstract

PURPOSE: A pharmaceutical composition for preventing and treating diabetes and complication of diabetes which contains Chrysanthemum indicum L. extract is provided to widely use for diabetes patients. CONSTITUTION: A pharmaceutical composition for preventing and treating diabetes and complication of diabetes contains Chrysanthemum indicum L. extract. The Chrysanthemum indicum L. extract is contained in 0.5-50 weight% based on total weight. The extract is isolated using low alcohol of 1-4 carbon atoms or their mixture solvent with water, acetone, chloroform, methylenechloride, ether and ethylacetate.

Description

Pharmaceutical composition comprising extracts of Chrysanthemi Flos for treating and preventing diabetes and diabetic complications

The present invention relates to a pharmaceutical composition for the prevention and treatment of diabetes mellitus, diabetic complications containing the extract.

Diabetes mellitus is a serious chronic metabolic disease, with 194 million people with diabetes worldwide in 2003, more than 300 million at risk of developing diabetes, and by 2025 WHO 300 million. It is expected to grow to 33 million (Pharmaceutical Newspaper, August 28, 2003). About 90% of people with diabetes are type 2 diabetes. (World Health Organization, Fact sheat 236, http://www.who.int/inf-fs/en/fact236.html 1999; Accessed July 25, 2002). Globally, it is estimated that at least $ 53 billion will be spent each year for the treatment of diabetics between the ages of 20 and 79. It is predicted that the cost of medical care will reach $ 21.3 billion to $ 396 billion by 2025. Given the huge medical expenditures and the large population exposure to diabetes, it is urgent to develop preventive, therapeutic and complications for the diabetes.

Type I diabetes mellitus is an immune mediated disease that is chronically and selectively disrupted by pancreatic β-cells. As a result, the destruction of insulin-secreting β-cells leads to a deficiency of insulin, resulting in hyperglycemia, diabetes, polydipsia and weight loss. These complications include increased likelihood of blindness, kidney failure, neurological disease and heart disease.

In Type II diabetes mellitus, the earliest dysfunction is insulin resistance in which insulin sensitive cells do not respond to normal levels of insulin (Consensus Development conference on Insulin Resistance 5-6 November 1997, American Diabetes Association, Diabetes). Care, 1998; 21: 310-314. To overcome this insulin resistance, β-cells of the pancreas increase insulin secretion, but over time, β-cell function deteriorates and thus insulin secretion decreases, thus hyperglycemia appears. Type 2 diabetes is caused by a combination of insulin's impaired hepatic glucose excretion, insulin's impaired glucose uptake into muscle and fat cells, and deterioration of β-cell function (DeFronzo RA, Bonadonna RC, Ferrannini). E, Pathogenesis of NIDDM, A balanced overview, Diabetes Care, 1992; 15: 318-368). Insulin resistance is an important cause for the development of a wide variety of diabetic complications. Insulin resistance refers to a decrease in the response of tissues to insulin action, resulting in insulin resistance syndrome (IRS), syndrome X, metabolic syndrome, and multiple metabolism. It is called plurimetabolic syndrome, new world syndrome, Syndrome X +, deadly quartet or diabetes obesity [Zimmet, P. Addressing the insulin resistance syndrome. A role for the thiazolidinediones, 2002]. Insulin resistance involves impaired glucose uptake by insulin, glucose intolerance, hyperinsulinemia, an increase in very low density lipoprotein triglycerides, a decrease in HDL cholesterol and hypertension [Reaven , GM Banting lecture. Role of insulin resistance in human disease. Diabetes 37, 1595-1607, 1988]. Overall obesity, central obesity, epigastric obesity, arteriosclerosis, melanoma, polycystic ovary syndrome, hyperuricemia, increased plasmainogen activator inhibitor-1 (PAI-1), impaired thrombolysis, vascular endothelial And smooth muscle dysfunction and microproteinuria are also included in insulin resistance syndrome [Peter, P., Nuttall, SL, Kendall, MJ Insulin resistance-the new goal !. J. Clinical Pharmacy and Therapeutics 28, 167-174, 2003]. Recent studies have shown that sleep apnea [Punjabi, N. M., Ahmed, M. M., Polotsky, V. Y., Beamer, B. A., O'Donnell, C. P. Sleep-disordered breathing, glucose intolerance, and insulin resistance. Respiratory Physiology & Neurobiology 136, 167-178, 2003], prostate cancer [Barnard, RJ, Aronson, WJ, Tymchuk, CN, N Sea, TH Prostate cander: another aspect of the insulin-resistance syndrome, Obesity reviews 3, 303- 308, 2002], type 1 diabetes [Greenbaum, CJ Insulin resistance in type 1 diabetes. Diabetes Metab. Res. Rev. 18, 192-200, 2003], affective disorders [Rasgon, N., Jarvik, L. Insulin resistance, affective disorders, and Alzheimer's disease: review and hypothesis. J. Gerontol. A Biol. Sci. Med. Sci. 59, 178-183, 2004], Alzheimer's disease [Watson, G. S., Craft, S. The role of insulin resistance in the pathogenesis of Alzheimer's disease: implications for treatment. CNS Drugs. 17, 27-45, 2003], stroke [Kernan, W. N., Inzucchi, S. E., Viscoli, C. M., Brass, L. M., Bravata, D. M., Horwits, R. I. Insulin resistance and risk for stroke. Neurology 59, 809-815, 2002], Breast Cancer [Stoll, B. A. Upper abdominal obesity, insulin resistance and breast cancer risk. Int. J. Obes. Relat. Metab. Disord. 26, 747-753, 2002, inflammation [Perseghin, G., Petersen, K., Shulman, G. I. Cellular mechanism of insulin resistance: potential links with inflammation. Int. J. Obes. Relat. Metab. Disord. 27 Suppl. 3, S6-S11, 2003], rheumatoid arthritis [Dessein, P. H., Joffe, B. I., Stanwix, A. E. Inflammation, insulin resistance, and aberrant lipid metabolism as cardiovascular factors in rheumatoid arthristis. J. Rheumatol. 30, 1403-1405, 2003] has also been suggested to be associated with diabetes complications caused by insulin resistance. Well-known diabetic complications include diabetic retinopathy, diabetic foot disease, diabetic nephropathy, diabetic neuropathy, various infections caused by diabetes, periodontal disease, skin disease, glycoside-containing hepatomegaly, fatty liver, cirrhosis, hepatitis, Acute pancreatitis, chronic pancreatitis, diabetic diarrhea, constipation, monolithic esophagitis, atrophic gastritis, and acute gastric dilated disease [Diabetes, Korean Diabetes Association, 1992]. Hyperglycemia due to diabetes is recognized as a major cause of hypertrophy, functional change and apoptosis in cells. Therefore, substances that lower blood sugar to normal and prevent cell death will play a major role in the prevention and treatment of diabetes and diabetic complications.

It is an object of the present invention to provide a pharmaceutical composition comprising the extract of gamguk, which is nontoxic and safe for the human body and which can be used for the prevention and treatment of diabetes mellitus and diabetic complications.

Providing a pharmaceutical composition that can be used for the prevention and treatment of diabetes mellitus and diabetic complications by scientifically verifying the prophylactic and therapeutic effects of diabetes mellitus and the complications of ginseng extract.

The composition comprising the extract of the country has a prophylactic and therapeutic effect of diabetes mellitus, diabetic complications, can be used comprehensively useful for diabetics.

The present invention relates to a composition for the prevention and treatment of diabetes mellitus, diabetic complications comprising the extract. The composition for the prevention and treatment of diabetes mellitus, diabetic complications of the present invention comprises 0.5 to 50% by weight of the extract of gakguk with respect to the total weight of the composition.

Guam is Latin Chrysanthemi Flos, common name is Chrysanthemum, scientific name is Chrysanthemum morifolium Ramat. (Compositae), Chrysanthemum indicum L. (Compositae), which contains Apigenin, Apigetrin16-beta-Hydroxy-3-O-palmityl-pseudotaraxasterol, 16-beta-Hydroxypseudotaraxasterol, Chlorogenic acid, Chrysanediol A, Chrysanthediacetate Chrysanthediacetate C, 3,5-Di-O-caffeoylquinic acid, Diosmetin-7-O-beta-D-glucopyranoside, Pseudotaraxasterol, Taraxasterol, Acacetin, Acacetin-7-O-beta-D-galactopyranoside, Acaciin, 8-Acetoxy- 2- (hexa-2,4-diynylidene) -1,6-dioxaspiro- [4.5] -dec-3-ene, Angeloylajadin, Arteglasin A, Artemisia-trans-spiroketalenoether polyne, Buddleoglucoside, Chamazulene, Chrysanthemol, Chrysanthetriol, Cumambrin A , Daucosterol, Fargesin, Handelin, 2- (Hexa-2,4-diynylidene) -1,6-dioxaspiro- [4.5] -dec-3-ene, Indicumenone, Luteolin, Parthenolide, Penduletin, (+)-Sesamin, Tanacetin [TradiMed Database 1996, Natural Products Research Institute]. There is no toxicity so anyone can eat with confidence and taste sweet. Known physiological actions include relaxing the gastrointestinal tract, improving the pulse of the intestine, and facilitating blood circulation. In addition, it is known to treat dizziness and headache, to replenish vision and blood, and to prevent aging.

It is also known to stimulate the antiviral effect and brain function to improve concentration and memory. However, there is no report that the country is effective in diabetes and diabetic complications.

The present inventors who have been working to develop a substance for preventing and treating diabetes and diabetic complications from natural products have found out that ginseng extract can be used as a hypoglycemic agent, an antidiabetic agent, a prophylactic and therapeutic agent for diabetic complications, and completed the present invention. .

Persimmon extract of the present invention can be prepared according to the following method.

Extraction Method: To a gamguk, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent of lower alcohol and water or a mixed solvent of these lower alcohols and water, acetone, chloroform, methylene chloride, ether and ethyl acetate are added. In this case, an available fraction can be obtained. The reaction temperature is preferably 5 to 80 ℃, preferably 30 to 55 ℃, the reaction time is 15 minutes to 48 hours, preferably 30 minutes to 12 hours.

In addition, the persimmon extract of the present invention may be subjected to an additional fractionation process by pH adjustment by a conventional fractionation method (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis. 3rd Ed. Pp 6-7, 1998 ).

The composition comprising the persimmon extract of the present invention may further comprise at least one component selected from the group consisting of pharmaceutically acceptable carriers and additives according to conventional methods.

Carriers that may be included in the composition comprising the extract of the present invention of the present invention generally include a substance called an excipient or a diluent, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, Maltitol, starch, isomerized sugar, sucrose, acacia rubber, alginate, gelatin, calcium, phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxy One or more components selected from the group consisting of benzoate, paraoxybenzoate, methyl paraoxybenzoate, paraoxypropylbenzoate, talc, magnesium stearate and mineral oil can be used.

In addition, additives that may be included in the composition comprising the sweetened extract of the present invention, natural carbohydrates, flavoring agents, nutrients, vitamins, minerals (electrolytes), flavoring agents (synthetic flavoring agents, natural flavoring agents, etc.), colorants, fillers (Cheese, chocolate, etc.), pactic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonating agents and pulp One or more components can be used.

Compositions comprising the persimmon extract according to the present invention, respectively, oral formulations of powders, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like according to conventional methods; External preparations; It can be formulated in the form of suppositories or sterile injectable solutions.

The amount of persimmon extract may vary depending on the age, sex, and weight of the patient, but the amount of 0.1-500 mg / kg may be administered once to several times daily. In addition, the dosage of the extract and its fraction may be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age, etc., and the dosage does not limit the scope of the present invention in any aspect. Since the persimmon extract itself of the present invention has little toxicity and side effects, it can be used with confidence even for long-term use for the purpose of prevention.

The persimmon extract of the present invention may also be used as a food or beverage, such as various foods, beverages, gums, teas, vitamin complexes and health supplements with food acceptable additives.

In this case, in the food comprising the persimmon extract according to the present invention, the persimmon extract may be included in 0.1 to 15% by weight, preferably 1 to 10% by weight relative to the total weight of the food.

In addition, in the beverage comprising the persimmon extract according to the present invention, the persimmon extract may be included in a ratio of 1 to 30g, preferably 3 to 10g based on 100ml of the beverage.

In addition, as a food-acceptable additive included in the food or beverage according to the present invention, natural carbohydrate, flavoring agent, nutrient, vitamin, mineral (electrolyte), flavoring agent (synthetic flavoring agent, natural flavoring agent, etc.), coloring agent , Fillers (cheese, chocolate, etc.), pactic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonating agents and pulp One or more components selected may be used.

The additive is preferably included in the range of 0.01 to 25 parts by weight per 100 parts by weight of the food or beverage composition.

In addition, natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; And sugar alcohols such as xylitol, sorbitol, and erythritol, which are generally used in an amount of about 1 to 20 g, preferably about 5 to 12 g per 100 m 1 of the beverage composition.

Flavoring agents include, but are not limited to, natural flavoring agents such as taumartin, stevia extracts (e.g., Rebaudioside A, glycyrzin, etc.); And synthetic flavors such as saccharin and aspartame.

The beverage composition of the present invention has no particular limitation on the liquid component, except that it comprises the persimmon extract as an essential ingredient in the proportions indicated.

Hereinafter, the present invention will be described with reference to the preparation of specific formulations, but the present invention is not limited to these examples.

Experimental Example 1. Preparation of gamguk extract

1) Experiment Method

Persimmon extract of the present invention may be prepared by the following manufacturing process.

First step: Gam-guk consists of lower alcohol having 1 to 4 carbon atoms such as methanol and ethanol, mixed solvent of lower alcohol and water, lower acetate such as ethyl acetate, acetone, chloroform, dichloromethane, carbon tetrachloride, methylene chloride, ether or hexane In an organic solvent selected from the group or a mixed solvent thereof, preferably a mixed solvent in the range of 1: 0.2 to 1.5 of methanol or methanol and water, at a temperature of 5 to 80 ° C., preferably at 30 to 55 ° C. for 15 minutes to 48 Extraction for a reaction time of time, preferably 30 minutes to 12 hours to obtain a lower alcohol soluble fraction.

In addition, the persimmon extract of the present invention may be subjected to the following fractionation process by a conventional fractionation method (Carborne J. B. Photochemical methods: A guide to modern techniques of plant analysis. 3rf Ed. Pp 6-7, 1998). .

Second step: The lower alcohol soluble fraction obtained above is dissolved in a mixed solvent of lower alcohol and water, adjusted to pH 2-4 with acid, and further extracted with the same amount of chloroform to obtain a chloroform soluble fraction.

The third step is to obtain a chloroform: methanol soluble fraction by extracting and fractionating the fraction which is not dissolved in the chloroform solvent to pH 9-12 with ammonium hydroxide, and extracting with the same amount of chloroform: methanol mixed solvent, wherein the chloroform: The mixing ratio of the methanol mixed solvent is preferably in the range of 1: 0.1 to 1. Among the fractions which are not dissolved in chloroform, the fractions dissolved when extracted with the chloroform: methanol mixed solvent contain most of the alkaloids, and the fractions that are dissolved in methanol in the fractions that are not soluble in the chloroform: methanol mixed solvent. The part contains quaternary alkaloids and N-oxides.

Step 4: A fraction which is not dissolved in the chloroform: methanol mixed solvent is further extracted and fractionated with methanol to obtain a methanol soluble fraction.

The present invention provides a composition for the prevention and treatment of diabetes mellitus, diabetic complications, including lower alcohol soluble fraction, chloroform soluble fraction, chloroform-methanol soluble fraction, methanol soluble fraction obtained from each step.

Experimental Example 2. Weight Measurement

1) Experiment Method

Changes in body weight were measured before oral administration (100 mg / kg, PO) for 30 days before and after the administration of persimmon extract.

2) Experiment result

In the normal group, the body weight increased normally over time from the initial weight of 23g to the final weight of 28g. However, in the diabetic group, normal weight gain did not occur, so the final weight was similar to the initial weight. When the extract was administered for 30 days, the normal weight gain inhibition by diabetes was blocked and showed the same weight gain pattern as the normal group (Table 1). This effect of the extract was induced to a similar degree to gliclazide. Diabetic group compared body weight with normal group. The diabetic + diabetic or diabetic + glycrazid administered group was compared with the diabetic group. Values shown are mean ± standard deviation (n = 6) ( ^# , p <0.05; NS indicates non significant; n = 6).

Initial weight (g) Final weight (g) Normal 23.08 ± 1.91 28.38 ± 3.39 Diabetes 24.03 ± 1.55 ^NS 24.92 ± 1.66 ^# Diabetic + Immunization group 24.02 ± 1.60 ^NS 27.95 ± 2.19 ^# Diabetic + Glyclazide Administration Group 24.32 ± 1.11 ^NS 28.18 ± 1.51 ^#

Experimental Example 3. Hypoglycemic Activity of Extracts

1) Experiment Method

30 minutes after oral administration of 100 g / kg of gamguk extract, glucose is administered to the mice (1 g / kg, s.c). After 90 minutes, blood was collected from the tail vein of the mouse and blood glucose was measured using a glucometer.

2) Experiment result

Glucose (1g / kg) was administered 30 minutes after oral administration of 70% MeOH extract of Gam-guk, and blood glucose was measured after 90 minutes, resulting in a significant hypoglycemic effect compared to the group treated with glucose alone. The level was restored (FIG. 1).

Experimental Example 3 Diabetes Inhibitory Effect of Korean Extracts: Hypoglycemic Effects Using Streptozotocin-induced Diabetic Mice

1) Experiment Method

Intraperitoneal administration (100 mg / kg) of streptozotocin (100 mM citrate buffer, pH 4.5) was performed in mice, and fasting blood glucose was measured 4 days later to confirm the induction of diabetes (J Gene Med. 2003, 5, 417-424). Persimmon extract and standard drug glyclazide were dissolved and prepared in 1% Tween 80 (v / v in water), followed by continuous administration for 30 days once a day. Blood was collected from the mouse tail vein and blood glucose was measured with a glucometer.

2) Experiment result

In the diabetic group that did not receive the extract, the blood sugar level was 173mg / dl. In the diabetic group, the blood sugar was significantly reduced to 126mg / dl for 30 days. This showed an excellent anti-diabetic effect similar to the blood sugar level of 118 mg / dl after 30 days of the standard glycoside drug glycide group (50 mg / kg, P.O.) (Fig. 2).

Experimental Example 5. Inhibition of Diabetic Complications from Korean Extracts (Inhibition of Cell Death)

1) Experiment Method

1. Persimmon extract (100mg / kg, PO) was administered once daily for 30 days, liver and kidneys were separated, washed with ice-cold saline, dried and dissolved buffer (100mM Tris HCl (pH 8.0), 20mM EDTA, 0.8% SDS) was added and homogenized, and then proteinase K (0.4ug / ml) was added and incubated at 50 ° C for 3 hours. Then, add phenol: chloroform: isoamyl alcohol (25: 24: 1), mix, centrifuge at 13,000 rpm for 10 minutes, and extract DNA. Two volumes of ice-cold absolute ethanol and 1/10 volume of 3 M sodium acetate are added to a DNA-containing aqueous layer and reacted at 4 ° C for 30 minutes to precipitate DNA. The DNA precipitate obtained by centrifuging the DNA at 13,000 rpm for 10 minutes at 4 ° C is washed with 1 ml 70% ethanol. After resuspension of the extracted DNA in Tris-EDTA buffer, 5ug of DNA was electrophoresed in 1.5% agarose gel and stained with EtBr. DNA bands were observed under UV light.

2) Experiment result

Compared to the normal group (I) in the liver (FIG. 3), the diabetic group (II) had a marked cell death and DNA fragmentation was induced. In the case of the administration of Korean extract (100mg / kg, P.O.) once daily for 30 days (III), cell death was significantly suppressed compared to the diabetic control group (II) and maintained at almost normal level. The inhibitory effect of hepatic extract on liver cell death was similar to that by glycrazid (IV), a diabetes standard drug.

In the kidney (FIG. 4), compared with the normal group (I), the diabetic group (II) had a marked cell death and DNA fragmentation was induced, and the administration of Gamguk extract (100 mg / kg, PO) once daily for 30 days (III) , Compared with the diabetic control group (II), significantly inhibited cell death and remained almost normal. The inhibitory effect of liver extract on liver cell death was similar to that of glycrazid (IV), a diabetes standard drug.

Formulation Example 1 Tablet

According to the following composition, each was formulated by a conventional tablet manufacturing method.

1-1. Tablet composition

Methanol extract 50.0 mg

Lactose 50.0 mg

Talc 0.5 mg

Magnesium Stearate 0.1 mg

1-2. Tablet composition

Persimmon Water Extract 50.0 mg

Lactose 50.0 mg

Talc 0.5 mg

Magnesium Stearate 0.1 mg

Formulation Example 2 Capsule

According to the following composition, a capsule was prepared in the following manner. The gamguk extract was sieved, mixed with excipients, and filled into gelatin capsules to prepare capsules.

2-1. Capsule Composition

Methanol extract 50.0 mg

Starch 1500 1.0 mg

Magnesium Stearate BP 10.0 mg

2-2. Capsule Composition

50.0 mg of water extract from Korea

Starch 1500 1.0 mg

Magnesium Stearate BP 10.0 mg

Formulation Example 3 Syrup

According to the following composition, a syrup was prepared in the following manner. First, white sugar was dissolved in purified water, paraoxybenzoate, paraoxypropylbenzoate, and persimmon extract were added thereto, dissolved at 60 ° C, cooled, and purified water was added to make 150 ml.

3-1. Syrup Composition

Methanol extract 50.0 mg

95.1 g per bag

Paraoxybenzoate 80.0 mg

Paraoxypropylbenzoate 16.0 mg

Purified water to 150 ㎖

3-2. Syrup Composition

Persimmon Water Extract 50.0 mg

95.1 g per bag

Paraoxybenzoate 80.0 mg

Paraoxypropylbenzoate 16.0 mg

Purified water to 150 ㎖

Formulation Example 4 Liquid

The following components were formulated in a conventional liquid formulation method, and filled into a brown bottle to prepare a liquid formulation.

4-1. Liquid composition

Methanol Extract 500.0 mg

Isomerized sugar 20.0 g

Antioxidant 5.0 mg

Methyl Paraoxybenzoate 2.0 mg

Purified water to 100.0 ml

4-2. Liquid composition

Persimmon Water Extract 500.0 mg

Isomerized sugar 20.0 g

Antioxidant 5.0 mg

Methyl Paraoxybenzoate 2.0 mg

Purified water to 100.0 ml

Formulation Example 5 Powder

The following components were mixed by a conventional powder production method, and put into a bag to seal the powder.

5-1. Powder composition

Methanol extract 50.0 mg

Lactose 100.0 mg

Talc 5.0 mg

5-2. Powder composition

Persimmon Water Extract 50.0 mg

Lactose 100.0 mg

Talc 5.0 mg

Formulation Example 6 Injection

The following components were filled into 2.0 ml ampoules by a conventional method for preparing an injection and sterilized to prepare an injection.

6-1. Injectable Composition

Methanol extract 50.0 mg

Antioxidant 1.0 mg

Tween 80 1.0 mg

Distilled water for injection to 2.0 ml

6-2. Injectable Composition

Persimmon Water Extract 50.0 mg

Antioxidant 1.0 mg

Tween 80 1.0 mg

Distilled water for injection to 2.0 ml

Formulation Example 7 Preparation of Wire

Brown rice, barley, glutinous rice, and jute radish were alphanated by a known method and then dried to be roasted, and then ground into a powder having a particle size of 60 mesh. Black beans, black sesame seeds and perilla were also steamed and dried in a known manner, and then ground to a powder having a particle size of 60 mesh. Granules were prepared by combining the grains, seeds and dried persimmon extract prepared above in the following proportions.

7-1. Wire manufacturing example

Cereals: Brown rice 30% by weight, Young radish 15% by weight, Barley 20% by weight, Glutinous rice 9%

Seeds: perilla 7% by weight, black beans 8% by weight, black sesame seeds 7% by weight,

Dry Powder of Methanol Extract of Persimmon Soup: 3% by weight, Ganoderma lucidum 0.5% by weight, Turmeric 0.5% by weight

7-2. Wire manufacturing example

Cereals: Brown rice 30% by weight, Young radish 15% by weight, Barley 20% by weight, Glutinous rice 9%

Seeds: perilla 7% by weight, black beans 8% by weight, black sesame seeds 7% by weight,

Dry powder of water extract of persimmon soup: 3% by weight, ganoderma lucidum 0.5% by weight, sulfuric acid 0.5% by weight

1 is a diagram showing the hypoglycemic effect of the extract. Values shown are mean ± standard deviation (n = 5) and significance for control is **: p <0.01; ***: P <0.001.

Figure 2 is a diagram showing the hypoglycemic effect of the extract. Values shown are mean ± standard deviation (n = 5) and significance for control is ***: P <0.001.

Figure 3 is a diagram showing the effect of inhibiting liver complications of the extract of gakguk.

Figure 4 is a diagram showing the effect of inhibiting kidney complications of the extract of gakguk.

Claims (9)

Pharmaceutical composition for the prevention and treatment of diabetes mellitus, diabetic complications comprising the extract. The composition of claim 1, wherein the extract is comprised from 0.5 to 50% by weight, based on the total weight of the composition. The method according to claim 1, characterized in that the extract is obtained by extracting a lower alcohol having 1 to 4 carbon atoms or a mixed solvent of these lower alcohols with water, acetone, chloroform, methylene chloride, ether and ethyl acetate. Composition. The composition of claim 1, wherein said composition further comprises at least one component selected from the group consisting of pharmaceutically acceptable carriers and additives.  The composition of claim 1, wherein the composition is formulated in oral or sterile injectable solution. Health functional food for the prevention and improvement of diabetes mellitus, diabetic complications, comprising the composition according to claim 1 and food-acceptable additives. The health functional food according to claim 6, wherein the persimmon extract is contained in an amount of 0.1 to 15 wt% based on the total weight of the food. 7. The method according to claim 6, wherein the food acceptable additives are natural carbohydrates, flavoring agents, nutrients, vitamins, minerals, flavors, coloring agents, fillers, fact acids and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners. Health functional food, characterized in that at least one component selected from the group consisting of pH adjusters, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation and pulp. The health functional food according to claim 6, wherein the health functional food is a beverage and the persimmon extract is contained in an amount of 1 to 30 g per 100 ml of the beverage.

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