KR100481114B1 - Pharmaceutical Composition for Decreasing Blood Glucose Level Containing Fermentation Product of the Extract of Banaba, Fenugreek and Bitter Mellon as a Effective Ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for lowering blood glucose, and more particularly, to have a diabetic effect, and to lower blood sugar, which contains a fermented product obtained by solid-fermenting banaba extract, fenugreek extract and bitter gourd extract as active ingredients. It relates to a pharmaceutical composition. The pharmaceutical composition for lowering blood glucose of the present invention exhibits potent glycemic control function and insulin resistance improvement, inhibits diabetic complications, and is secured as a natural medicine, and thus may be useful for preventing or treating diabetic diseases.

Description

Pharmaceutical Composition for Decreasing Blood Glucose Level Containing Fermentation Product of the Extract of Banaba, Fenugreek and Bitter Mellon as a Effective Ingredient}

The present invention relates to a blood sugar lowering composition, and more particularly, to a blood sugar lowering composition having an improvement effect on diabetic symptoms and containing a fermentation product of banaba extract, fenugreek extract and bitter gourd extract as an active ingredient.

Diabetes mellitus is a non-infectious chronic disease, in which the insulin secreted from the pancreatic β cells is insufficient or does not function properly, so glucose is not used as an energy source in the body and remains high in blood and excreted in the urine.

Diabetes often tends to coexist with hypertension, hyperlipidemia and obesity, and this series of symptoms is called insulin resistance syndrome (or X-syndrome) or metabolic syndrome. In this case, obesity is usually accompanied, and atherosclerosis progresses rapidly, leading to atherosclerotic heart disease. According to one report, the incidence of metabolic syndrome in Koreans is 19% in adult men and 16% in adult women, which is three times the frequency of diabetes. In particular, obesity is a cause of chronic lifestyle diseases such as atherosclerosis cardiovascular disease, diabetes mellitus, hypertension and must be improved.

Diabetes can be broadly classified into insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) according to its pathogenesis and treatment of symptoms. In Korea, more than 95% of diabetics are insulin-independent diabetics. Diabetes is not a big disease in itself but rather a complication caused by long-term disease, such as diabetic neuropathy, retinopathy, cataract, nephropathy, etc. This is a social problem because patients can not only live a normal life but can have fatal consequences.

Currently used diabetic improvement drugs are roughly divided into oral hypoglycemic agents and insulin injections. In general, insulin-dependent diabetes patients without insulin secretion, gestational diabetes patients, and insulin-independent diabetes patients whose blood glucose control is poorly controlled by oral hypoglycemic agents are given insulin injections, despite the combination of diet and exercise therapy. Insulin-independent diabetic patients who are not controlled to take oral hypoglycemic agents are generally used. Oral hypoglycemic agents may be classified into sulfonylurea drugs and biguanide drugs.

Sulfonylurea-based drugs such as glipizide, glyclazide, gliquidone, glibenclamide, and chlorpropamide have been shown to promote insulin secretion in the pancreas. It cannot be used in insulin-dependent diabetics who have no insulin secretion in the pancreas and cannot be used in women of childbearing potential due to concerns about insulin-independent diabetes patients with relatively decreased insulin secretion in the pancreas, birth defects, miscarriage and stillbirth. There is this. In addition, since most sulfonylurea-based drugs are metabolized in the liver and excreted into the kidney, they should be used with caution in patients with hepatic and renal function disorders.

Although biguanide-based drugs such as metformin have no clear mechanism of action, they have not been shown to increase insulin secretion in the pancreas, and have a lower hypoglycemic effect than sulfonylurea-based drugs. low. However, due to the high incidence of side effects of the digestive system, nausea, vomiting, diarrhea, rash, etc. appear at the beginning of treatment, and cause lactic acidosis, which causes life-threatening side effects, and is currently used only as an experimental drug in the United States. Doing.

Therefore, currently used sulfonylurea-based or biguanide-based drugs have the above-mentioned disadvantages or side effects, and thus can develop a safer hypoglycemic agent with less side effects and more desirable to better improve diabetic diseases at home and abroad. Necessity is emerging.

The present invention has been made to solve the problems of the conventional diabetes treatment as described above, as having a hypoglycemic activity and inhibitory activity of diabetic complications, aspergillus duck material ( Aspergillus oryzae ) in Banaba extract, fenugreek extract and bitter gourd extract It is an object of the present invention to provide a pharmaceutical composition for lowering blood sugar or a health functional food containing a fermented product inoculated with the strain as an active ingredient.

In order to achieve the above object, the present invention has a hypoglycemic activity and the inhibitory activity of diabetic complications, and the active ingredient solid fermented by inoculating Aspergillus duck material strain in Banaba extract, fenugreek extract and Yeoju extract It provides a pharmaceutical composition or health functional food for lowering blood sugar.

Hereinafter, the present invention will be described in detail.

First, the present invention provides a pharmaceutical composition for lowering blood sugar, which contains a fermented product fermented by solid inoculation of Aspergillus auria strains to the barnabas extract, fenugreek extract and gourd extract as an active ingredient.

In the pharmaceutical composition for lowering blood glucose of the present invention, the extract of banaba, fenugreek and bitumen is prepared by extracting banaba, fenugreek and bitumen by a conventional method using an organic solvent such as an aqueous alcohol solution, and the composition of the present invention is Banaba, fenugreek and Yeoju extract are inoculated with Aspergillus duck strain and prepared by solid fermentation.

1) extracting banaba, fenugreek and bitter gourd with water, alcohol or aqueous alcohol solution;

2) filtering and extracting the filtrate;

3) inoculating the concentrate with Aspergillus duck strain and then fermenting a solid; And

4) spray-drying, lyophilizing the fermented product.

In the above, the alcohol may be selected from the group consisting of methanol, ethanol, propanol and butanol, of which ethanol is preferably used. In addition, in the aqueous alcohol solution, the concentration of the aqueous solution is preferably 10 to 100%, more preferably 30 to 70%, and most preferably 50%. In a preferred embodiment of the present invention used an extract using 50% ethanol. In addition, the extract may be prepared by mixing together banaba, fenugreek and bitter gourd, or may be used after extracting each of the banaba, fenugreek and bitter gourd.

In preparing the composition of the present invention, the constituent ratios of the barnabas, fenugreek and bitter gourd extracts are preferably 5 to 40 wt (wt)%: 20 to 50 wt%: 20 to 50 wt%, and 20 wt%: More preferably, it is 40 wt%: 40 wt%.

In addition, the composition of the present invention may further ferment after containing soybean powder in the banaba, fenugreek and bitter gourd extract. The soybean powder is a powder dried boiled domestic soybeans, may be included in a ratio of about 1: 1 to the entire mixture of banaba, fenugreek and bitter gourd extract, the ratio may be changed to some extent.

In addition, the composition of the present invention may further contain vitamin mix 12, carboxac zinc and chromium-enriched yeast in the banaba, fenugreek, bitter gourd and soybean powder solid fermentation products. The vitamin mix 12, casolac zinc and chromium-enriched yeast may be further included in the composition of the present invention in amounts of 10-20 wt%, 5-15 wt% and 5-10 wt%, respectively.

Barnabas is a plant belonging to the “Buddhistaceae” with the scientific name Lagerstroemia spesiosa, from north Australia to the south, through the Philippine lowland, the Malay peninsula and the Indonesian peninsula to the north, to the south, and to the west. It is a deciduous tree widely distributed in the tropics leading to India. It is also called Yvonne name (big flower, crape myrtle). As the name suggests, Barnabas is a plant belonging to the same genus Crape myrtle, 5 to 20 cm in height, stems are not as crape myrtle, but smooth, and bark falls off irregularly. The leaf is thick oval with pointed front, large and 25 cm long. Banaba is a medicinal plant known from ancient times in Southeast Asia, and its leaves are used for the prevention and treatment of diabetes.

Fenugreek is well known under the name of fenugreek, a year-old bean family originating from the Mediterranean, and has been cultivated in the Middle East, Africa, India, etc. for food and medicinal purposes. Has been used. Seeds of fenugreek are used for spices such as curry, and in addition to folk remedies, it is also used for nourishing tonic, nutritional supplementation, food promotion and antipyretic. In particular, the literature has recently been reported to be effective in the treatment of diabetes (Gupta A. et al., J. Assoc. Physicians India, 49, 1,057-1,061, 2001).

Yeoju is also called bitter melon. The stem is thin and grows up to 1 ~ 3 m in length and is wound up by winding other things with tendrils. Fruits are gourds, long oval, narrow at both ends, hump-like projections, yellow-red, irregularly split, and covered with red flesh. It is called Yeoju because the fruit is similar to Yeoji. The young fruit and red seedling (種 皮) is used for food and the seed is used for medicinal purposes. It has recently been reported that it can be used for the treatment of diabetes (Miura T. et al., J. Nutr. Sci. Vitaminol., 47 (5), 340-344, 2001; Grover JK. Et al., J Ethnopharmacol., 76 (3), 233-238, 2001).

In the case of the composition of the present invention, it is thought that the active ingredients in the raw materials are transferred to various useful components through the fermentation process, and in particular, various enzyme components are produced through fermentation, and low molecular weight of proteins (analytical results show that low molecular peptides of 80% or more of soy protein). ), And also its usefulness can be maximized, such as the synthesis of vitamins and the transfer of functional ingredients into active forms. Diabetes, which is caused by poor metabolism of glucose in the blood, can help improve and prevent diabetes by metabolizing active components in solid fermentation products and activating enzymes and cellular functions.

The present inventors confirmed that the pharmaceutical composition for hypoglycemic of the present invention has hypoglycemic activity. To this end, the hypoglycemic activity and the inhibitory activity of diabetic complications of the composition of the present invention against streptozotocin-induced diabetes were measured. As a result, it was confirmed that the composition of the present invention exhibits an excellent hypoglycemic activity and sorbitol inhibitory activity in each tissue, and also exhibits a hypoglycemic activity similar to that of Epalestat, a known diabetic disease treatment agent used as a comparative group. (See Table 1 and Table 6).

In particular, the present invention is a hypoglycemic pharmaceutical composition is diabetic retinopathy, diabetic neuropathy, nephropathy, which is a degenerative complication caused by diabetes due to the accumulation of sorbitol in tissues such as the lens, erythrocytes or sciatic nerve as chronic diabetes progresses It may also be useful in complications such as atherosclerosis, myocardial disorders, skin disorders, diabetic foot syndrome and peripheral vascular disease. That is, the composition of the present invention can prevent the development of diabetic complications by inhibiting the accumulation of sorbitol, which is also possible by inhibiting the activity of the aldose reductase of the polyol pathway. At present, many studies have been conducted to inhibit the complications by inhibiting aldose reductase involved in the first step of the polyol pathway for the control of such complications such as cataracts, retinopathy and kidney disease.

Therefore, the composition of the present invention not only has an excellent preventive effect on the expression of metabolic syndrome, but also exhibits a hypoglycemic activity comparable to the known blood glucose inhibitor metformin even in patients with elevated blood sugar levels, thereby preventing or treating metabolic syndrome. It was confirmed that it can be usefully used.

The compositions of the present invention can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical formulations. Preferred pharmaceutical preparations include tablets, hard or soft capsules, oral preparations such as liquids, suspensions, and parenteral injections such as injectable solutions or suspensions, and these pharmaceutical preparations are conventionally pharmaceutically acceptable. Carriers such as excipients, binders, disintegrants, lubricants, solubilizers, suspending agents, preservatives or extenders in the case of injectables, stabilizers, preservatives, dissolution aids, buffers or isotonic agents in injections. A topical agent etc. can be used.

The dosage of the hypoglycemic pharmaceutical composition of the present invention may be determined by a specialist depending on various factors such as the severity of the diabetic disease, the patient's condition, age, sex, and complications, but in general, an adult (about 50 kg in weight) From 500 to 1,000 mg per day, preferably from 300 mg to 400 mg. It is also intended to contain a daily dose of the pharmaceutical composition, or a half, 1/3 or 1/4 thereof, per unit dosage form, and may be administered 1 to 6 times per day.

Banaba, fenugreek and yeast, which are the raw materials of the pharmaceutical composition of the present invention, are all secured as natural plant materials, and in particular, when the composition of the present invention is orally administered to rats, the toxicity results are obtained. The 50% lethal dose (LD ₅₀ ) by the test was found to be a safe material of at least 10 g / kg or more.

In addition, the present invention provides a blood glucose lowering health food containing the banaba extract, fenugreek extract and bitter gourd extract as an active ingredient.

When the extract is used as a food, it may be used as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). In general, in the preparation of food or beverages, the banaba extract, fenugreek extract and bitter gourd extract are added in an amount of 10 to 90 wt%, preferably 30 to 70 wt%, based on the raw materials. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be less than the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. It is certain.

There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

Example 1 Preparation of Composition for Improving Blood Sugar and Improving Diabetes (1)

<1-1> Preparation of Banaba Extract

The present inventors soaked 2 kg of banaba in distilled water (20 L) for 24 hours and dried. The dried banaba was extracted with 50% ethanol (10 L) five times at room temperature, and then concentrated under reduced pressure and spray-dried to banaba extract (28.3). g) was prepared. It was confirmed that the content of corosolic acid (Corosolic acid), which is an indicator component, of the barnabas extract was 3% or more.

<1-2> Preparation of Fenugreek Extract

The present inventors soaked 2 kg of fenugreek in distilled water (20 L) for 24 hours, dried, extracted dried banaba with 50% ethanol (10 L) five times at room temperature, and then powdered with a reduced pressure concentrator and a spray dryer. (30.1 g) was prepared. It was confirmed whether the content of galactomannan, which is an indicator component of the fenugreek extract, is 80% or more.

<1-3> Preparation of Yeoju extract

The present inventors soaked 2 kg of Yeoju in distilled water (20 L) for 24 hours, dried, extracted dried Banaba with 50% ethanol (10 L) five times at room temperature, and then concentrated under reduced pressure and spray-dried to make Yeoju extract (37.61 g) was prepared.

<1-4> Preparation of Composition

The inventors weighed 5 g, 10 g, and 10 g of the banaba extract, fenugreek extract and bitter gourd extract, respectively, and homogeneously mixed, and then, as a spawn, yellow mold, Aspergillus duck, KFRI 00888 (ATCC 22887) 0.1 After inoculating%, the composition for treating diabetes of the present invention was prepared by incubating solid for 36 to 42 hours at a temperature of 30 to 32 ° C. and a humidity of 70 to 85% RH. At this time, 0.001% of biotin was added to promote the culture.

Example 2 Preparation of a Diabetic Improvement Composition (2)

The present inventors soaked 200 g of domestic soybeans in distilled water (2 L) for 24 hours, boiled in hot water, steamed and cooled to 32 ℃. After further mixing 25 g of domestic soybean soaked in 5 g, 10 g and 10 g of Banaba extract, Fenugreek extract and Yeoju extract prepared in Example 1, respectively, in the same manner as in Example <1-4> After inoculating 0.1% of the spawn yellow fungus Aspergillus duck material KFRI 00888 (ATCC 22887), and incubated solid for 36 to 42 hours in a temperature of 30 ~ 32 ℃, humidity 70 ~ 85% RH culture room for diabetes treatment of the present invention The composition was prepared. At this time, 0.001% of biotin was added to promote the culture.

Example 3 Preparation of a Diabetic Improvement Composition (3)

The present inventors add the vitamin mix 12 3.0 g, 2.0 g of kasolak zinc, 1.0 g of chromium-enhanced yeast to 30 g of the diabetic improvement composition of the present invention prepared in Example 2, and then mixed homogeneously to diabetes of the present invention. An improvement composition was prepared.

The vitamin mix 12 is powder vitamin A 3.4%, powder vitamin E 13.5%, vitamin C 36.0%, vitamin B ₆ hydrochloride 1.4%, vitamin B ₁ nitrate 1.0%, folic acid 0.12%, vitamin B ₁₂ (1%) 0.16%, Powdered Vitamin D ₃ 0.95%, Pantothenate Calcium 3.4%, Nicotinamide 6.8%, Biotin (1%) 1.8%, Vitamin B ₂ 0.8%, Inositol 0.67%, Maltodextrin 20%, Lactose 10%, etc. It is prepared by mixing.

Casolac zinc is a composition made by chelating zinc with amino acids to increase zinc utilization in the body.L-lysine 25.27%, glycine 12.20%, zinc oxide 1.5%, vitamin C 0.03%, and purified water 61.0% Stir until completely dissolved. After stirring, the filtrate is powdered through a drum dryer or a spray dryer. Casorac zinc contained about 10% of zinc and was purchased from KH Hood.

Chromium fortified yeast was made by adding Chromium Chloride (Chromic Chloride) to brewer's yeast broth to increase chromium content in beer yeast. It was manufactured by Lalemamd Co. of Canada and purchased from Vision Biochem Co., Ltd.

<Comparative Example 1> Preparation of the composition for improving diabetes (4)

The present inventors prepared a composition for treating diabetes by weighing 5 g, 10 g, and 10 g of Banaba extract, Fenugreek extract and Yeoju extract prepared in Example 1 and mixing them homogeneously.

Experimental Example 1 Antidiabetic and Complication Inhibition Experiment

<1-1> Plasma glucose concentration measurement

10 weeks old male rats (Sprague-Hawley) using the normal group, the control group, the composition of the present invention prepared according to Examples 1 to 3 and Comparative Example 1, and the Epalestat administration group as Comparative Example 2 each 10 The diabetes was induced by dividing and dissolving streptozotocin in 0.05 M citric acid (pH 4.5) once administered 66 mg / kg intraperitoneally. Two weeks after the induction of diabetes, 200 mg / kg of saline, the composition prepared according to Examples 1 to 3 and Comparative Example 1, and epalestat were orally administered. Two weeks later, blood was collected under ether anesthesia, followed by extraction of the lens and sciatic nerve. The collected blood was divided for blood glucose measurement and quantitation of sorbitol content in red blood cells. Blood was centrifuged to obtain serum and quantified with glucose measurement kit reagent.

As a result, the blood glucose was significantly increased in the control group administered with streptozotocin only as significant as compared to the normal group, and the composition administration group of the present invention showed a significant decrease compared to the control group. In particular, the composition of the present invention prepared in Example 3 exhibited an excellent hypoglycemic effect than Epalestat, a treatment for diabetic disease, which is classified as an aldose reductase inhibitor, and the effect of the composition of Comparative Example 1 was not fermented. Excellent The results are summarized in Table 1 below.

group Blood sugar (g / ℓ) % Inhibition Normal group (no kill) 1.2 ± 0.08 - Control group (only streptozotocin administered) 5.7 ± 0.33 - Composition Administration in Example 1 4.0 ± 0.30 29.8 Composition Administration in Example 2 3.9 ± 0.29 31.6 Composition Administration in Example 3 3.8 ± 0.31 33.3 Composition Administration of Comparative Example 1 4.5 ± 0.31 21.1 Comparative Example 2 (Epalestat administration) 3.9 ± 0.24 31.6

<1-2> Glucose Tolerance Test

Eleven-week-old male rats were divided into 10 groups of the control group, the composition-administered group of the present invention and metformin-administered groups prepared according to Examples 1 to 3 and Comparative Example 1, respectively, and the rats were fasted for 16 hours before the glycosylation experiment. Each group was orally administered saline, 300 mg / kg of the composition prepared according to Examples 1 to 3 and Comparative Example 1, and 250 mg / kg of metformin. After 30 minutes, 3 g / kg of glucose was orally administered to all groups, and blood glucose was measured by collecting blood from the orbital vein immediately before glucose administration, three times after glucose administration 60, 120 and 180 minutes.

As a result, it was observed that blood glucose in the glucose-loaded rats showed a significant decrease after 2 hours of glucose administration compared to the control group, resulting in a glucose tolerance. In particular, the composition of the present invention exhibited a hypoglycemic effect similar to that of metformin, a biguanide-based hypoglycemic agent, and was superior to the composition of Comparative Example 1 not fermented. The results are summarized in Table 2 below.

group 0 hours 1 hours 2 hours 3 hours Control group (only streptozotocin administered) 55.5 ± 1.9 160.3 ± 4.8 189.7 ± 4.0 132.1 ± 3.4 Composition Administration in Example 1 47.6 ± 3.8 191.5 ± 12.9 139.3 ± 8.8 124.3 ± 4.4 Composition Administration in Example 2 46.2 ± 3.3 188.7 ± 8.9 137.3 ± 8.5 124.1 ± 4.0 Composition Administration in Example 3 45.9 ± 3.6 185.0 ± 8.3 135.1 ± 7.2 123.7 ± 4.2 Composition Administration of Comparative Example 1 47.4 ± 3.8 193.5 ± 10.9 141.3 ± 8.2 127.2 ± 4.4 Comparative Example 2 (Metformin Administration) 54.5 ± 2.2 140.1 ± 7.0 122.8 ± 1.4 139.6 ± 4.5

<1-3> aldose reductase inhibitory effect

Preparation of the enzyme source for measuring the aldose reductase inhibitory effect was performed by slightly modifying the method used by Hayman. Specifically, the lens of the rat was extracted and homogenized by adding a certain amount of phosphate buffer solution according to the wet weight. After centrifugation at 4 ° C, the supernatant was taken up and saturated with ammonium sulfate to 40%. The supernatant was centrifuged and added to ammonium sulfate until it became 70%. The precipitate was obtained by centrifugation. Was suspended in a minimum amount of buffer for about 1 day for dialysis and then used as an enzyme source.

The enzyme source prepared above and DL-glyceraldehyde were reacted as a substrate, and the rate of decrease of NADPH absorbance was measured at 340 nm. Tetramethylene glutaric acid (TMG) was used as an aldose reductase inhibition standard.

As a result, the composition of the present invention showed a dose-dependent inhibitory activity against aldose reductase isolated from the rat lens and the results are shown in Table 3.

Sample concentration (㎍ / ㎖) Inhibition rate [% of control value] 50% inhibitory concentration (㎍ / ㎖) TMG 1.86 87.4 0.67 0.19 42.4 0.02 22.4 Composition of Example 1 100 95.9 23.7 10 46.4 5 29.9 Composition of Example 2 100 96.1 21.8 10 47.1 5 30.1 Composition of Example 3 100 96.4 20.1 10 49.4 5 31.4

<1-4> Sorbitol content measurement

In order to measure the content of sorbitol in the red blood cells in the collected blood, pretreatment was as follows. That is, 5 ml of blood was centrifuged, and the precipitate was washed three times with cold saline solution, 1 ml was taken, 3 ml of 6% perchloric acid was added, and the protein was precipitated by centrifugation. 1 ml of 2.5 M potassium carbonate was added to the supernatant, neutralized, centrifuged, and the sorbitol content was measured by taking the supernatant (protein-free filtrate). Sorbitol content was measured according to the Clements method. Specifically, 1 ml of the reaction mixture (glycine buffer pH 9.4, 0.2 mM nicotinamide adenosine dinucleotide, 0.64 U sorbitol dihydrogenase) was mixed with 0.5 ml of supernatant, and then reacted for 25 minutes, and then the sorbitol content in the red blood cells was measured using a fluorescent photometer. Measured. In the case of isolated lens and sciatic nerve, lyophilization was followed by homogenization (homogenization) in 1.5 ml distilled water, followed by centrifugation, and the supernatant was treated in the same manner as above to measure the sorbitol content in the lens and sciatic nerve.

As a result, the sorbitol content in erythrocytes showed a significant increase in the control group administered with streptozotocin only compared to the normal group, and the group administered with the composition of the present invention showed a significant decrease in the sorbitol content in the red blood cells compared to the control group. . In particular, the composition of the present invention showed a sorbitol content-reducing effect similar to that of epalestat, a diabetic disease agent, which is classified as a diabetic complication agent, and showed an effect superior to that of the composition of Comparative Example 1. The results are summarized in Table 4 below.

group Sorbitol in erythrocytes (nmol / mg dry weight) % Inhibition Normal group (no kill) 63.2 ± 3.9 - Control group (only streptozotocin administered) 403.6 ± 61.3 - Composition Administration in Example 1 145.3 ± 12.8 64.0 Composition Administration in Example 2 142.1 ± 12.1 64.8 Composition Administration in Example 3 137.6 ± 10.9 65.9 Composition Administration of Comparative Example 1 195.7 ± 13.1 51.5 Comparative Example 2 (Epalestat administration) 108.7 ± 11.6 73.1

In addition, the sorbitol content in the lens showed a significant increase in the control group administered only streptozotocin compared to the normal group, but the group administered with the composition of the present invention showed a significant decrease compared to the control group. In particular, the composition of the present invention showed an effect of inhibiting sorbitol in the lens similar to that of Epalestat, a diabetic disease treatment agent classified as a treatment for diabetic complications, and the results are shown in Table 5.

group Sorbitol (nmol / mg dry weight) in lens % Inhibition Normal group (no kill) 0.05 ± 0.02 - Control group (only streptozotocin administered) 0.80 ± 0.04 - Composition Administration in Example 1 0.38 ± 0.10 52.5 Composition Administration in Example 2 0.37 ± 0.07 53.3 Composition Administration in Example 3 0.37 ± 0.04 53.8 Composition Administration of Comparative Example 1 0.46 ± 0.10 42.5 Comparative Example 2 (Epalestat administration) 0.38 ± 0.05 52.5

In addition, the sorbitol content in the sciatic nerve showed a significant increase in the control group administered only streptozotocin compared to the normal group, but the composition administration group of the present invention showed a significant decrease compared to the control group. In particular, the composition of the present invention showed an effect of inhibiting sorbitol in the sciatic nerve similar to that of epalestat, a diabetic disease treatment agent classified as a diabetic complication agent, and the results are shown in Table 6.

group Sorbitol (nmol / mg dry weight) in lens % Inhibition Normal group (no kill) 2.0 ± 0.3 - Control group (only streptozotocin administered) 10.4 ± 1.4 - Composition Administration in Example 1 7.2 ± 0.5 30.8 Composition Administration in Example 2 7.0 ± 0.4 32.7 Composition Administration in Example 3 6.7 ± 0.3 35.6 Composition Administration of Comparative Example 1 7.6 ± 0.4 26.9 Comparative Example 2 (Epalestat administration) 4.3 ± 0.5 58.7

From the results shown in Table 1 to Table 6, the composition of the present invention effectively lowers the blood sugar level in the diabetic model animals induced by the administration of streptozotocin and shows the effect of glucose tolerance in the glycoside experiment, aldose which is a cause of diabetic complications Since it exhibits an inhibitory effect of reductase and sorbitol accumulation, it can be used as an effective prophylactic or therapeutic agent for diabetic diseases including complications of diabetes mellitus, and it was confirmed that there is an excellent effect than the unfermented composition used as a comparative example.

Experimental Example 2 Oral Acute Toxicity in Rats

Acute toxicity test was performed using 6-week-old specific pathogen-free (SPF) SD rats. Five animals per group were suspended in 0.5% methylcellulose solution in a composition of the invention according to Examples 1 to 3 once in doses of 1 g / kg, 5 g / kg and 10 g / kg. Oral administration. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed, and hematological and hematological examinations were performed.

As a result, no significant clinical symptoms or dead animals were noted in all animals treated with the test substance, and no toxic changes were observed in weight changes, blood tests, blood biochemical tests, and autopsy findings. As a result, the composition for treating diabetes of the present invention does not show a toxicity change in rats up to 10 g / kg, and thus the intermediate dose of oral administration (LD ₅₀ ) is prepared according to Examples 1 to 3 It was determined to be a safe substance that was at least g / kg.

Preparation Example 1 Preparation of Composition

<1-1> Preparation of Soft Capsule

100.0 mg of the composition of the present invention prepared according to Example 1, 329.0 mg of wheat germ oil, 45.0 mg of sulfur, 21.0 mg of soybean phospholipid, 5.0 mg of D-α tocopherol, the contents of the total 500 mg, the capsule base is gelatin 212.0 mg, Glycerin (specific gravity 1.24) 50.0 mg, di-sorbitol 76.0 mg, paraoxybenzoic acid methyl 0.54 mg, paraoxybenzoic acid propyl 0.90 mg, methyl vanillin 0.56 mg, yellow 203 No. It was prepared according to the preparation of capsules.

<1-2> Preparation of Tablet

100.0 mg of the composition of the present invention prepared according to Example 2, 175.0 mg of inulin, 210.0 mg of crystalline cellulose, 10.0 mg of carboxymethyl cellulose calcium, and 5 mg of magnesium stearate were added and mixed, and the tablets were tableted to 500 mg.

<1-3> Preparation of capsule

100.0 mg of the composition of the present invention prepared according to Example 3, 175.0 mg of inulin, 220.0 mg of crystalline cellulose, and 5 mg of magnesium stearate were homogeneously mixed and filled to contain 500 mg in one capsule.

Preparation Example 2 Preparation of Food

The present inventors prepared the food or beverage composition containing the blood glucose lowering composition of this invention as an active ingredient as follows.

<2-1> Preparation of Chewing Gum

Gum Base 20%

Sugar 76.36-76.76%

0.24 to 0.64% of the composition of the present invention

1% of fruit flavor

Water 2%

Chewing gum was prepared using conventional methods using the above composition and content.

<2-2> Preparation of Candy

50 to 60% sugar

Starch syrup 39.26 ～ 49.66%

0.24 to 0.64% of the composition of the present invention

Orange flavor 0.1%

Candy was prepared using conventional methods with the above composition and content.

<2-3> Preparation of Biscuits

Force Class 1 88 kg

Gravity First Class 76.4 ㎏

16.5 kg per white

2.5 kg of salt

2.7 kg of glucose

Palm shortening 40.5 kg

5.3 kg of ammo

Medium kg 0.6 kg

0.55 kg sodium bisulfite

Rice flour 5.0 kg

Vitamin B1 0.003 kg

0.003 kg of vitamin B2

Milk Flavor 0.16 ㎏

71.1 kg of water

Whole milk powder 4 kg

Substitute powder 1 kg

0.1 kg of calcium phosphate

Spray salt 1 kg

25 kg of spray oil

0.1 to 0.5 kg of the composition of the present invention

Biscuits were prepared using conventional methods with the above composition and content.

<2-4> Preparation of Ice Cream

Milkfat 10.0%

Non-fat solids 10.8%

12.0% sugar

Starch syrup 3.0%

Emulsifying Stabilizer (Span) 0.5%

Spice (Strawberry) 0.15%

Water 63.31-62.91%

0.24 to 0.64% of the composition of the present invention

Ice cream was prepared using conventional methods using the above composition and content.

<2-5> Preparation of Drink

522 mg of honey

Chioctosanamide 5 mg

Nicotinamide 10 mg

Riboflavin Sodium Hydrochloride 3 mg

Pyridoxine hydrochloride 2 mg

Inositol 30 mg

Orthoic acid 50 mg

0.48-1.28 mg of the composition of the present invention

200 ml of water

With the above composition and content, drinks were prepared using conventional methods.

<2-6> preparation of sausage

Pork 63.6%

Chicken 27.5%

Starch 3.5%

Soy Protein 1.7%

Salt 1.62%

Glucose 0.5%

Other additives (glycerine) 0.94 ~ 1.34%

0.24 to 0.64% of the composition of the present invention

Sausages were prepared using conventional methods using the above composition and content.

<2-7> Preparation of Chocolate

Sugar 34.36-34.76%

Cocoa Butter 34%

Cocoa Mass 15%

Cocoa Powder 15%

Lecithin 0.5%

0.5% vanilla

0.24 to 0.64% of the composition of the present invention

With the above composition and content, chocolate was prepared using conventional methods.

As described above, the blood glucose lowering composition of the present invention exhibits a strong hypoglycemic activity and inhibits diabetic complications and is secured as a natural plant component, which is useful for preventing or improving diabetic diseases and inhibiting diabetic complications. Can be.

Claims (4)

delete delete A pharmaceutical composition for lowering blood glucose, comprising a fermented product obtained by inoculating a Aspergillus duck material strain in 20 wt% of banaba extract, 40 wt% of fenugreek extract, and 40 wt% of yeast extract as an active ingredient. delete