KR20060033837A - Antidiabeitic composition containing the extracts of mulberry leaves and fenugreek seed - Google Patents

Abstract

The present invention relates to a composite composition for preventing and treating diabetes, including a mulberry leaf extract and fenugreek extract, and more specifically, mulberry leaf extract containing more than 0.4% by weight of 1-deoxynojirimycin (1-deoxynojirimycin) and 4 The present invention relates to a composition having an antidiabetic effect having improved blood glucose lowering ability by including a fenugreek extract containing at least 5% by weight of 4-hydroxyhyleucine (4-Hydroxyisoleucine).

Mulberry leaf extract, fenugreek extract, diabetes, hypoglycemic

Description

Antidiabetic composition containing mulberry leaf extract and fenugreek extract {Antidiabeitic composition containing the extracts of mulberry leaves and fenugreek seed}             

1 is a graph showing changes in blood glucose of normal mice according to a sample.

Figure 2 is a graph showing the change in blood glucose of the rat induced diabetes according to the sample.

The present invention relates to a composite composition for preventing and treating diabetes, including a mulberry leaf extract and fenugreek extract, and more specifically, mulberry leaf extract containing more than 0.4% by weight of 1-deoxynojirimycin (1-deoxynojirimycin) and 4 The present invention relates to a composition having an antidiabetic effect having improved blood glucose lowering ability by including a fenugreek extract containing at least 5% by weight of 4-hydroxyhyleucine (4-Hydroxyisoleucine).

As the standard of living increases, metabolic diseases (diabetes, osteoporosis, etc.) are rapidly increasing due to increased fat intake, decreased physical activity, and increased elderly population. Among these metabolic diseases, diabetes is the third most serious disease in the world. Currently, 250 million people of the world population are estimated to be diabetic, and Korea is estimated to be 3 to 5 million people with diabetes.

Diabetes is an imbalance of hormones such as insulin, glucagon, and glucocorti-coid, resulting in abnormal physiological metabolic control functions such as carbohydrates, proteins, lipids, and electrolyte metabolism. And diabetes mellitus, which are characteristic of the disease and bring about serious chronic complications.

Diabetes mellitus, insulin-dependent diabetes mellitus (type 1 diabetes) and insulin resistance, which are caused mainly by autoimmune processes that destroy pancreas β-cells, can cause insulin secretion. It is classified as insulin-independent diabetes mellitus (type 2 diabetes) due to interactions such as causes and reduced function of beta cells.

In the case of insulin-dependent diabetes, the use of insulin has become a common treatment. In the case of insulin-independent diabetes, diet and exercise are the primary treatments, but insulin and oral when the blood sugar levels are not satisfactory. The use of a dosage form is a common method.

However, most of the antidiabetics currently used in hospitals and the like are chemically synthesized materials. Therefore, the antidiabetic agent, which is a chemical compound, may cause problems such as side effects and toxicity. In order to solve this problem, researches on natural products have been actively conducted in recent years to develop anti-diabetic substances.

Mulberry leaf extract is a plant herbal medicine obtained from the extract of the mulberry leaf belonging to the Moraceae family, the main component is rich in gamma aminobutyl acid, rutin in addition to 1-deoxynojirimycin with a hypoglycemic action, It is known that it contains a fluorine (fagomine), 2-aryl-benzofuran derivatives (etc.).

Until now, studies on the physiological activity of mulberry leaves include hypoglycemic effect by inhibition of alpha glucosidase activity (kimura M, Chen FJ, Nakashimqa N, Koya S. Anti Hyperglycemic effect of N-containing sugars delived) from Mulberry leaves in streptozocin-induced diabetic mice, J Traditional medicine 12: 214-219, 1995).

The fenugreek ( Trigonella foenum-graecum, Fenugreek) is an annual plant legume. Fenugreek is the word for "the hay of Greece" and is named after the smell of dried hay. The main components of fenugreek include alkaloids and proteins such as gentianine, choline, and carpaine.

Among the components of fenugreek, 4-Hydroxyisoleucine has the property of stimulating the secretion of insulin from the pancreas, and fenugreek shows excellent effect in Glucose tolerance test. It is known because of high fiber content. It is known that fenugreek has a function of lowering blood sugar, but does not affect blood clotting at all.

According to a 2002 report by the Mada team of the Jewish University of Jerusalem in Israel, published in the British Journal of Nutrition, fenugreek seeds consist of 23 to 26 percent protein, 6 to 7 percent fat and about 58 percent carbohydrates. , About 25% of which is made up of dietary fiber ("New legume sources as therapeutic agents". British Journal of Nutrition. (2002), 88, Suppl. 3. S287-S292).

4-hydroxyisoleucine, a key activity indicator of fenugreek extract, is a small molecule of molecular weight 147.17, molecular formula C ₆ H ₁₃ NO ₃ , containing only about 0.56% of fenugreek seeds in the Broca of the French National Center for Pharmaceutical Research. A team of professors also revealed in 1999 ["4-Hydroxyisoleucine: experimental evidence of its insulinotropic and antidiabetic properties". American Journal of Physiology. (1999) 277, E617-E623.

That is, as described above, it can be seen that the effect of the fenugreek extract on the anti-diabetic has been the most attention, and the representative studies that observed the efficacy of the fenugreek extract on the anti-diabetic include the following. .

In 1997, a team of professors Srivastava at the University of Odense, Denmark, conducted a double-blind trial on 60 patients with normal and diabetic patients. The powders of garlic extract and fenugreek extract, which are known to be closely related, were administered to four groups of 15 people each for a total of three months. In the garlic extract group, blood sugar, blood lipids and cholesterol, No significant difference was shown. On the other hand, in the group administered with the powder of fenugreek extract, the blood glucose level of the patients with insulin-independent diabetes mellitus (type 2 diabetes) decreased by about 15% after one month. In addition, blood lipids and cholesterol were demonstrated to be reduced in similar proportions, demonstrating the excellent antidiabetic effect of fenugreek seed-derived 4-hydroxyisoleucine ["Effect of ginger and Fenugreek on blood lipids, blood sugar and platelet aggression in patients" with coronary artery disease ". Prostaglandin, Leukotrienes and Essential Fatty Acids. (1997) 56 (5), 379-384.

In 2001, Gupta's team at the Jaipur General Hospital in India also conducted a clinical trial on antidiabetics, and as a result, all 25 patients with type 2 diabetes had secreted blood sugar, blood lipids and insulin at 15 to 30 days. Excellent improvement was observed in major indicators of diabetes, including glucose tolerance ("Effect of Trigonella foenum-graecum (Fenugreek) Seeds on Glycaemic Control and Insulin Resistance in Type 2 Diabetes Mellitus: A Double Blind Placebo Controlled Study". JAPI, Vol. 49, November 2001. 1057-1061).

However, the case of applying fenugreek extract showing excellent antidiabetic properties as described above to the actual diet has not been reported yet.

Accordingly, the inventors of the present invention find the proper content of the active ingredient that can express the most improved blood sugar improvement properties in consideration of the characteristics of the mulberry leaf extract and fenugreek extract as described above, By adjusting the addition ratio of mulberry leaf extract and fenugreek extract to the range where the synergistic effect of blood sugar improving properties is best expressed, it can be easily ingested in real life, and the composite composition showing anti-diabetic properties due to its excellent blood sugar improving properties The present invention was completed to know that it can be prepared.

Therefore, the present invention uses a mixed mulberry leaf extract containing more than 0.4% by weight of 1-deoxy nojirimycin and fenugreek extract containing more than 5% by weight of 4-hydroxyisorucin to increase the hypoglycemic effect, and also has side effects and It includes mulberry leaf extract and fenugreek extract that have the effect of preventing and treating diabetes that can overcome the limitations of existing anti-diabetic agents such as toxicity and make foods and health functional foods available to the general public more easily. The purpose is to provide a composite composition.

The present invention comprises a mulberry leaf extract containing at least 0.4% by weight of 1-deoxy nojirimycin, and fenugreek extract containing at least 5% by weight of 4-hydroxyisoruycin in a 25 to 75: 25 to 75 weight ratio prevention and It is characterized by a therapeutic composite composition.

This invention will be described in detail.

The present invention is to find the appropriate content of the active ingredient that the mulberry leaf extract and fenugreek extract can express the most excellent blood sugar improvement characteristics, the mulberry leaf extract and fenugreek in the range that the active ingredient is the most excellent synergism of the blood sugar improvement characteristics A blending ratio of leek extracts is controlled, and includes mulberry leaf extract powder containing 0.4% by weight or more of 1-deoxynojirimycin and fenugreek extract powder containing 5% by weight or more of 4-hydroxyisorucin. It is applied to food so that it can be easily consumed in real life.

The main component of the composition of the present invention is a mulberry leaf extract. Mulberry leaf extract is obtained by drying the mulberry leaf powdered and then put in 50% ethanol (EtoH) aqueous solution 2-3 times at 30 ~ 70 ℃. At this time, the amount of the ethanol aqueous solution is suitable 3 to 5 times the volume of mulberry leaves. The separated extract was evaporated and concentrated under the conditions of 30 ~ 70 ℃, the extract was powdered by heating or lyophilization, it was confirmed that containing 1-deoxy nojirimycin 0.4% by weight or more by HPLC.

The content of 1-deoxy nojirimycin as an effective ingredient in the blood sugar drop to be used in the present invention among the mulberry leaf extract is 0.4% by weight or more, preferably 0.4 to 3.0% by weight, wherein the 1-deoxynojiri If the amount of mycin is less than 0.4% by weight effective effect is not expressed and may cause a manufacturing problem that must use a large amount of mulberry leaf extract.

Another major component of the composition of the present invention is fenugreek extract. Fenugreek seeds have a bitter taste and aroma, so they are used as medicines in ancient India, Greece, and Arabia, and as Indian curry, Egyptian bread, and North African coffee substitutes.

In the present invention, to obtain an extract containing a large amount of 4-hydroxyisoleucine, an active ingredient having a hypoglycemic effect from fenugreek seeds that were limited in the use of such spices and to apply it to foods of various uses.

Fenugreek extract is obtained by putting fenugreek seeds in water (H ₂ O) and solvent extraction 2-3 times at 30 ~ 70 ℃. At this time, the amount of water is suitable about 3 to 5 times the volume of fenugreek seed. The separated extract was evaporated and concentrated under the conditions of 30 ~ 70 ℃, the extract was powdered by heating or lyophilization, it was confirmed that the 4-hydroxyisoleucine is contained at least 5% by weight using HPLC.

The content of the above 4-hydroxyisoleucine is 5% by weight or more, preferably 5.0 to 20% by weight. At this time, when the content of the 4-hydroxyisorucin is less than 5% by weight, a problem arises in that a large amount of fenugreek extract is used to obtain a blood sugar lowering effect.

The composition of the present invention is also characterized by further strengthening the blood sugar lowering properties of the mulberry leaf extract and fenugreek extract, the respective mulberry leaf extract and fenugreek extract separately.

That is, the composition of the present invention is used by mixing the mulberry leaf extract and fenugreek extract in a 25 to 75: 25 to 75 weight ratio. If the mixing ratio is out of the above range, the synergistic effect of the hypoglycemic properties is not preferably achieved, it is better to comply with the above range.

Such a composition of the present invention includes the above-mentioned mulberry leaf extract and fenugreek extract as a main component, and may optionally include components such as seed oil, silk protein, ginkgo leaf extract, and various other vitamins.

That is, the content of the evening primrose seed oil, silk protein, ginkgo biloba extract, and various other vitamins is preferably 10 to 50% by weight in the total composite composition, more specifically 5 to 15% by weight of evening primrose oil, silk 5-15% protein and 2-10% by weight of ginkgo biloba extract may be prepared to prepare a composite composition, which may be applied to food and health functional food. The complex composition may use a variety of vitamins, for example, vitamin A, vitamin B ₁ , vitamin B ₆ , vitamin C and vitamin E.

The composition excellent in hypoglycemic efficacy of the present invention can be applied to food in a variety of ways, and is not particularly limited, but specifically, for example, food can be applied to biscuits, beverages, etc., tablets, capsules, granules, It can be prepared as a formulation such as pills and applied as a health functional food.

Food or health functional foods to which the composition of the present invention is applied as described above has the advantage that there are no side effects that may occur even when taking long-term use.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by the following Examples.

EXAMPLES Preparation of Composite Composition (Composition 1) of the Present Invention

180 mg of powder of mulberry leaf extract (1-deoxynojirimycin content 0.42% by weight), 270 mg of powder of fenugreek extract (5.0% by weight of 4-hydroxyisoruycin), evening seed oil 8 mg, powder of ginkgo leaf extract A total of 480 mg of a composite composition was prepared comprising 3 mg, silk protein 7 mg, vitamin B ₁ 2 mg, vitamin B ₆ 2 mg, vitamin C 6 mg, vitamin E 2 mg.

Experimental Example 1 Mouse Experiment

1) Experiment Outline

To determine the hypoglycemic effect of the sample, a hypoglycemic effect was compared by performing an Oral Maltose Tolerance Test using a 5-week-old ICR mouse in SPF (Specific Pathogen Free).

2) Experiment Method

The ICR mice (male, 25 g) purchased from Orient Co., Ltd. were adapted for 7 days in an animal feeding room and fasted for 20 hours to use only mice with a blood glucose level of 55 to 75 mg / dL. Each experimental group consisted of 10 animals, and the test conditions are shown in Table 1 below.

Each sample was orally administered using a zoned syringe, blood was collected from the tail vein, and the blood glucose of the collected blood was measured using a Super Glucocard II blood glucose meter (manufactured by Nihon ARKRAY). Animal breeding room was adjusted to a constant temperature and humidity conditions of 22 ± 2 ℃, humidity 65 ± 2%, the contrast was turned off at 8:30 pm after turning on the lamp at 8:30 in the morning.

3) Experiment result

The hypoglycemic effect of the mouse measured by the above experimental method was measured 45 minutes after the administration of the sample, the average value and the standard deviation are shown in Table 1 below.

As shown in Table 1, according to the maltose tolerance test, compared to the second group to which only maltose was administered, the third group using the powder of mulberry leaf extract was 28.2%, 4 using the fenugreek extract powder. It can be seen that the group exhibits a 19.7% hypoglycemic effect.

In particular, the group 5 using the complex composition of the mulberry leaf extract powder and fenugreek extract powder of the present invention mixed in an appropriate ratio showed a blood glucose lowering effect of 33.2%, the composite of the present invention prepared according to the above embodiment Group 6 with the composition showed a hypoglycemic effect of 34.2%. As seen here, the mulberry leaf extract or fenugreek extract was found to have a good effect on lowering blood sugar when treated with a mixture rather than a single treatment.

Group 7 showed 20.3% hypoglycemic effect compared to group 2 treated with maltose alone, and group 8 showed 28.0% hypoglycemic effect. there was.

 The results are shown graphically in FIG. 1.

Experimental Example 2 Rat Experiment

1) Experiment Outline

To investigate the hypoglycemic effect of the samples, each sample was orally administered to 5-week-old SD rats with SPF (Specific Pathogen Free) for 2 weeks, followed by 55 mg / kg of Streptozotocin (STZ). After a single intraperitoneal administration, the animals were reared for 2 weeks while being orally administered to confirm the change in blood sugar and body weight during this period.

Streptozotoxin is an N-nitroso derivative of D-glucosamine and was originally developed as an antibiotic, and is known to reduce intracellular NAD (nicotinamide adenine dinucleotide) and to destroy pancreatic beta cells to cause diabetes. .

2) Experiment Method

The environment of the animal breeding room is controlled at constant temperature and humidity (22 ± 2 ℃, 65 ± 2%), and the contrast is turned off at 8:30 pm after the lamp is turned on at 8:30 in the morning. The purchased SD rat (male, 80 ± 10 g) was used, and the rats were adapted for 7 days in the animal kennel, and each sample was orally administered using a zoned syringe at 11 am daily, and after 2 weeks, strepto Intraperitoneal administration of zotoxin was used to confirm the degree of diabetes. Participation of the sample was continued for 2 weeks after streptozotoxin administration to measure changes in blood glucose and body weight.

As feed, Purina experimental rat feed purchased from Biopia was used, and water was freely fed. Sigma Streptozotoxin was used as a diabetes-causing substance, and blood glucose was measured by using a Super Glucocard II blood glucose meter (manufactured by Nihon ARKRAY) by collecting blood from the tail vein of the rat.

Each group consists of 7 rats, and the composition of the samples administered in Table 2 is shown.

3) Experiment result

The blood glucose and weight changes measured as described above are shown in Tables 3 and 4, respectively, and the changes in blood glucose are shown in the accompanying drawings as a graph.

As shown in Table 3, the hypoglycemic effect was the most effective in groups 6 and 5.

In addition, compared with group 2 treated with streptozotoxin on the last day of blood glucose measurement, group 3 21.4%, group 4 22.3%, group 5 28.3%, group 6 28.7%, group 7 21.4%, group 8 22% Blood sugar reduction effect was shown.

As shown in Figure 2, when the oral administration of each sample to the rats for 2 weeks, the blood glucose level is gradually increased in 4, 5, 6, 7, 8 groups when streptozotoxin is administered. In particular, in the case of groups 5 and 6, the increase in blood glucose level is more gentle and the lowest blood glucose level is considered to have a diabetes prevention effect. In addition, among the mulberry leaf extract and fenugreek extract group 5, 6, 7 and 8 group, the difference in blood glucose lowering effect according to the concentration can be seen, among which the hypoglycemic effect was The largest.

As shown in Table 4 above, compared to group 2, which was administered streptozotoxin on the last day of the test, 32 days, Group 3 27.3%, Group 4 15.0%, Group 5 18.4%, Group 6 22.0%, Group 7 15.9% , 26.7% of group 8 showed weight loss inhibitory effect.

Experimental Example 3: Acute Toxicity in Oral Administration of Rats

Acute toxicity test was performed using SPF SD rats at 5 weeks of age. Three animals per group were suspended orally in a dose of 3 g / kg / 1.5 ml of the composite composition prepared according to the above example in a 0.5% methylcellulose solution.

After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed, and hematological and blood biochemical tests were performed. As a result, there were no clinical symptoms or deaths in all animals treated with the test substance, and no toxicity change was observed in weight change, blood test, blood biochemistry test, autopsy findings, etc. As a result, all of the compositions used in the experiment did not show toxicity change up to 3 g / kg of the composition in the rat.

Preparation Example 1 Preparation of Granules Containing Composition Excellent in Hypoglycemic Efficacy

Fenugreek extract (450 mg), Mulberry leaf extract (300 mg), Evening seed oil (8 mg), Silk protein (7 mg), Ginkgo leaf extract (3 mg), Vitamin B ₁ (3 mg), Vitamin B ₆ (3 mg ), Vitamin C (30 mg), vitamin E (3 mg) was prepared to include a granule.

Preparation Example 2 Preparation of Capsules Comprising Compositions Excellent in Hypoglycemic Efficacy

Fenugreek extract (270 mg), Mulberry leaf extract (180 mg), Evening seed oil (8 mg), Silk protein (7 mg), Ginkgo biloba extract (3 mg), Vitamin B ₁ (2 mg), Vitamin B ₆ (2 mg ), Vitamin C (6 mg), vitamin E (2 mg) was prepared, including the accelerator.

Preparation Example 3: Preparation of a beverage containing a composite composition excellent in hypoglycemic efficacy

Fenugreek extract (210 mg), Mulberry leaf extract (140 mg), Evening seed oil (8 mg), Silk protein (7 mg), Ginkgo leaf extract (3 mg), Vitamin B ₁ (2 mg), Vitamin B ₆ (2 mg), vitamin C (30 mg), vitamin E (2 mg), vitamin A (5 mg), iron lactate (2 mg), water (suitable) was prepared.

As described above, the present invention is a composition of a mulberry leaf extract containing more than 0.4% by weight of 1-deoxy nojirimycin and fenugreek extract containing more than 5% of 4-hydroxyisorucin is a mulberry leaf and fenugreek alone It was confirmed that there is a very excellent effect that provides a synergistic effect on blood sugar lower than when used as.

In addition, the present invention is a decoction seed oil, silk protein, ginkgo biloba leaves containing the composition of the mulberry leaf extract containing more than 0.4% by weight of 1-deoxy nojirimycin and fenugreek extract containing more than 5% by weight of 4-hydroxyisorucin Compositions prepared using food ingredients that are safe for human body such as extracts have a specific content to prevent diabetes and improve blood sugar, and apply them to food and health functional foods to prevent diabetes and improve blood sugar. You can expect the effect.

Claims (4)

Prevention of diabetes, comprising mulberry leaf extract containing at least 0.4% by weight of 1-deoxy nojirimycin and fenugreek extract containing at least 5% by weight of 4-hydroxyisorucin in a weight ratio of 25 to 75: 25 to 75 And therapeutic composite compositions. A composite composition for preventing and treating diabetes, characterized in that it comprises 10 to 50% by weight of one or more mixtures selected from evening seed oil, silk protein and ginkgo leaf extract in addition to the composite composition of claim 1. According to claim 2, wherein the composite composition is 5 to 15% by weight of evening primrose seed, 5 to 15% by weight of silk protein and 2 to 10% by weight of ginkgo leaf extract complex composition for preventing and treating diabetes. Food for preventing and treating diabetes, comprising the complex composition of any one of claims 1 to 3.

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