WO2018174502A1 - Pharmaceutical composition for preventing or treating diabetes mellitus comprising chrysanthemum leaf extract as active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating diabetes mellitus comprising a chrysanthemum leaf extract as an active ingredient, and a health functional food composition for preventing or ameliorating diabetes mellitus. It has been specifically confirmed that the chrysanthemum leaf extract according to the present invention decreases fasting blood glucose, plasma glucose, and plasma insulin, and improves insulin resistance such as inhibiting an increase of C-peptide content, etc., in a diet-induced obesity animal model. Accordingly, the chrysanthemum leaf extract can be effectively used to improve blood glucose and prevent, ameliorate, and treat diseases related to insulin resistance

Description

Pharmaceutical composition for preventing or treating diabetes, including chrysanthemum leaf extract as an active ingredient

The present invention relates to a pharmaceutical composition for preventing or treating diabetes comprising chrysanthemum leaf extract as an active ingredient, and more particularly to a composition for preventing, treating and improving diabetes comprising chrysanthemum leaf extract as an active ingredient. .

There are about 20 billion fat cells in the human body, which are responsible for accumulating or releasing energy in mammals. Fat cells store the energy consumed and stored in the form of triglycerides, and then break it down into free fatty acids and glucose when energy is depleted.

Diabetes, one of the diseases caused by fat accumulation as described above, is a disease in which glucose present in the blood is discharged through urine, and is one of chronic degenerative diseases that are not fundamentally cured. In modern times, due to changes in diet and lack of exercise, a great change occurred in the body's own energy metabolism process, resulting in an increase in chronic degenerative diseases such as diabetes. In Korea, the prevalence of diabetes is known to reach 5 to 10% and shows a continual increase. In the United States, diabetes has increased six-fold over the past 40 years, and the increase has led to the number of patients reaching 20 million by 2050. It is expected to lead to death.

These diabetes are classified into insulin-dependent diabetes (type 1 diabetes), insulin-independent diabetes (type 2 diabetes), and malnutrition diabetes (MRDM). Type 2 diabetes, which accounts for more than 90% of diabetic patients in Korea, is hyperglycemic. Metabolic disease characterized by the fact that genetic, metabolic, environmental factors caused by the decrease in insulin secretion of pancreatic beta cells or increased insulin resistance in peripheral tissues has been reported. In this regard, it is known that insulin sensitivity is decreased when body fat increases with diabetes mellitus, and abdominal fat accumulation is known to be related to glucose intolerance. In addition, since diabetes mellitus and insulin resistance have a close correlation in patients with type 2 diabetes, it is known that the more severe diabetes mellitus, the greater the insulin resistance. In addition, the pathogenesis of insulin independent diabetes mellitus (type 2 diabetes) is known as a complex disorder of insulin secretion and insulin resistance. Diabetes mellitus is a disease with chronic hyperglycemia due to this complex disorder.

On the other hand, insulin secretion disorder refers to a situation in which the proper amount of insulin is not secreted from the beta cells of the pancreas according to the blood glucose concentration, which includes both a quantitative decrease in the secretion of insulin secreting cells and a functional secretion disorder. Insulin resistance refers to a situation in which secreted insulin has reached the target organ in the bloodstream but its insulin action and sensitivity are degraded in the target cell, which is generally considered to be a signaling disorder after cell membrane receptor binding, and is a cause of genetic predisposition. , Diabetes, decreased physical activity and hyperglycemia or dyslipidemia. Insulin resistance requires higher levels of insulin to overcome resistance, and conversely, hyperglycemia caused by insufficient insulin secretion may worsen insulin resistance again.

The chrysanthemum is a flower that for perennial plants of chrysanthemum, chrysanthemum extract, antioxidant and anti-inflammatory effects that are known but (Korea Patent Publication No. 2010-033573), chrysanthemum leaves (Chrysanthemum morifolium Ramat leaf) belongs to the Asteraceae Efficacy is not clear.

The present inventors, while devoting to research on the development of a material having anti-diabetic effect, confirmed that chrysanthemum leaf extract can regulate blood sugar and improve insulin resistance, and completed the present invention based on this.

An object of the present invention is to provide a pharmaceutical composition for preventing or treating diabetes, including chrysanthemum leaf extract as an active ingredient.

Another object of the present invention is to provide a health functional food composition for preventing or improving diabetes, including chrysanthemum leaf extract as an active ingredient.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating diabetes, including chrysanthemum leaf extract as an active ingredient.

In one embodiment of the present invention, the composition controls blood sugar and improves insulin resistance, and the composition may lower blood sugar in the body and reduce insulin levels, thereby improving insulin resistance.

In another embodiment of the present invention, the chrysanthemum leaf extract is water, lower alcohols of C1 to C4, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof It may be extracted with a solvent selected from the group consisting of.

In another embodiment of the invention, the chrysanthemum leaf extract may comprise 1 to 5% by weight based on the total weight of the composition.

In addition, the present invention provides a health functional food composition for preventing or improving diabetes, including chrysanthemum leaf extract as an active ingredient.

The present invention also provides a pharmaceutical composition for treating or preventing insulin resistance-related diseases, including chrysanthemum leaf extract as an active ingredient.

The present invention also provides a health functional food composition for preventing or improving insulin resistance-related diseases, including chrysanthemum leaf extract as an active ingredient.

In addition, the present invention provides a method for preventing or treating diabetes, comprising administering the composition to a subject.

In addition, the present invention provides a use of the composition for preventing or treating diabetes.

Chrysanthemum leaf extract according to the present invention, when administered to a dietary obesity-induced mouse model, lowers fasting blood glucose, lowers plasma glucose and plasma insulin, and inhibits an increase in the C-peptide content. It was confirmed experimentally. Therefore, the chrysanthemum leaf extract is expected to be useful for improving blood sugar and preventing and treating diseases related to insulin resistance.

In addition, the present invention comprises chrysanthemum leaf extract as an active ingredient, characterized in that to regulate blood sugar and insulin secretion, can be used as a health functional food composition for the prevention or improvement of insulin resistance-related diseases.

1 is a diagram illustrating a schematic experimental design using a dietary obesity-induced mouse model in order to evaluate the glycemic control and insulin resistance improvement effect of chrysanthemum leaf extract.

FIG. 2 is a fasting blood glucose level of the normal diet group (ND), high fat diet group (HFD), chrysanthemum leaf extract low-dose feeding group (CLL), and chrysanthemum leaf extract high-dose feeding group (CLH) mice for 4 weeks, measured for 16 weeks. Figure showing the change in blood sugar according to the breeding period.

FIG. 3 is a glucose loading test to measure postprandial blood glucose levels of normal diet group (ND), high fat diet group (HFD), chrysanthemum leaf extract low dose feeding group (CLL), and chrysanthemum leaf extract high dose feeding group (CLH) mice. The blood glucose measurement is a diagram showing the results showing the blood glucose concentration in each time period based on the blood glucose concentration of 100 minutes.

4 is a view confirming the effect on the plasma glucose content control and insulin resistance improvement, (a) is a normal diet group (ND), high fat diet group (HFD), chrysanthemum leaf extract low dose feed group (CLL), and chrysanthemum leaf extract The high-dose feeding group (CLH) mice were bred for 16 weeks and then fasted for 12 hours, and fasted blood samples were measured to compare plasma glucose, and (b) is a comparison of C-peptide concentration change. ) Shows a comparison of changes in insulin concentration, and (d) shows a comparison of HOMA-IR, an insulin resistance indicator.

FIG. 5 is a graph showing changes in lipid profile of liver tissues of the normal diet group (ND), high fat diet group (HFD), chrysanthemum leaf extract low dose feeding group (CLL), and chrysanthemum leaf extract high dose feeding group (CLH) mice. .

Figure 6 is an experimental design using a dietary obesity-induced mouse model to compare the anti-diabetic effect of the chrysanthemum leaf alcohol extract (CLE1) and the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3) of the present invention Is a simplified diagram.

7 is a four-week-old male C57BL / 6J mice (n = 50) normal diet group (ND), high fat diet (HFD), chrysanthemum leaf alcohol extract of the present invention (CLE1, high fat diet + 1.5% chrysanthemum leaves Alcohol extract), the researched chrysanthemum flower hot water extract pay group (CLE2, high fat diet + 1.5% chrysanthemum flower hot water extract), and the chrysanthemum methanol extract pay group (CLE3, high fat diet + 1.5% chrysanthemum methanol extract) Each of the 10 dogs and breeding for 12 weeks, and shows the results of measuring fasting blood glucose at intervals of 4 weeks.

FIG. 8 shows normal diet group (ND), high fat diet group (HFD), chrysanthemum leaf alcohol extract feeding group (CLE1), chrysanthemum flower hot water extract feeding group (CLE2), and chrysanthemum methanol extract feeding group (CLE3) mice reared for 12 weeks. Figure 3 shows the results of comparative analysis by measuring plasma glucose, insulin content and HOMA-IR levels.

The present invention provides a pharmaceutical composition for preventing or treating diabetes, including chrysanthemum leaf extract as an active ingredient.

As used herein, the term "prevention" means any action that inhibits or delays the onset of diabetes by administration of the pharmaceutical composition according to the invention.

As used herein, the term "treatment" means all the actions that improve or beneficially change the symptoms for diabetes by administration of the pharmaceutical composition according to the present invention.

"Diabetes", which are diseases to be improved, prevented or treated by the present invention, are disorders caused by glycemic control disorders and insulin resistance.

Chrysanthemum morifolium Ramat leaf extract of the present invention is extracted from chrysanthemums, in particular for the 'leaf' portion, according to a conventional method known in the art for extracting extracts from natural products, that is, conventional It can extract using a conventional solvent under the conditions of temperature and pressure. For example, chrysanthemum leaf extract in the present invention is a group consisting of water, alcohol having 1 to 4 carbon atoms, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and a mixed solvent thereof It can be extracted using one or more solvents selected from, preferably using ethanol, more preferably 70% ethanol. In addition, the method of extracting the extract from the chrysanthemum leaves can be extracted through various methods such as hot water extraction, cold needle extraction, reflux extraction, ultrasonic extraction, but is not limited thereto.

The prepared extract can then be filtered or concentrated or dried to remove the solvent, it can be carried out both filtration, concentration and drying. For example, the filtration may be performed using a filter paper or a vacuum filter, the concentration may be a vacuum concentrator, the drying may be performed by a spray drying method, a freeze drying method, but is not limited thereto.

In addition, the extract extracted with the solvent may be further fractionated with a solvent selected from the group consisting of butanol, n-hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, and mixtures thereof. . The fractionation temperature may be 4 ℃ to 120 ℃, but is not limited thereto.

In one embodiment of the present invention, to evaluate the anti-diabetic effect of the chrysanthemum leaf extract extracted by the above method, the experiment was conducted using a high fat diet-induced obese mouse.

In an embodiment of the present invention, C57BL / 6J mice were classified into a normal diet group, a high fat diet group, a chrysanthemum leaf extract low-dose feeding group and a high-dose feeding group, and reared for 16 weeks to confirm the glycemic control effect of the chrysanthemum leaf extract (Example 3), it was confirmed that glucose tolerance was increased, thereby improving the disorder of glucose tolerance (see Example 4).

In addition, the results of the measurement of plasma glucose, C-peptide content, insulin content and HOMA-IR values showed that the levels of all the chrysanthemum leaf extract intake groups were significantly decreased to regulate plasma glucose content and improve insulin resistance. (See Example 5).

In one embodiment of the present invention, as a result of analyzing the effect of chrysanthemum leaf extract on liver tissue lipid profile change, it was confirmed that the liver cholesterol, triglyceride, and free fatty acid content is significantly reduced compared to the high fat diet group (HFD) (See Example 6).

In addition, in one embodiment of the present invention as a result of comparing and analyzing the effects on the fasting blood glucose, plasma glucose, insulin content and HOMA-IR by parking according to the extraction method and site of chrysanthemum, chrysanthemum flower hydrothermal water in the group of chrysanthemum leaf alcohol extract It was confirmed that the anti-diabetic effect was excellent compared to the extract and chrysanthemum methanol extract, showing an excellent fasting glucose lowering effect and an insulin resistance reducing effect (see Example 7).

Therefore, the effect of improving the blood glucose control and insulin resistance of the composition comprising the chrysanthemum leaf extract as an active ingredient, it was confirmed that it can be used as an active ingredient for the prevention, improvement or treatment of diabetes.

Chrysanthemum leaf extract of the present invention may include 1 to 5% by weight based on the total amount of the composition, preferably 2.5% by weight, more preferably 1.5% by weight, but not limited thereto. It doesn't happen.

The pharmaceutical composition according to the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient. At this time, the pharmaceutically acceptable carrier is commonly used in the formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose , Polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. In addition to the above components, it may further include a lubricant, wetting agent, sweetener, flavoring agent, emulsifier, suspending agent, preservative and the like.

The pharmaceutical compositions of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and the dosage is determined by the condition and weight of the patient, Depending on the extent, drug form, route of administration, and time, it may be appropriately selected by those skilled in the art.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level refers to the type of disease, the severity, the activity of the drug, It may be determined according to the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, factors including the drug used concurrently and other factors well known in the medical field. The pharmaceutical compositions according to the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, condition, weight of the patient, the absorption of the active ingredient in the body, the inactivation rate and excretion rate, the type of disease, the drug used in general 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight may be administered daily or every other day, or divided into 1 to 3 times a day. However, since the dose may be increased or decreased depending on the route of administration, the severity of diabetes, sex, weight, age, etc., the dosage does not limit the scope of the present invention by any method.

In another aspect of the present invention, the present invention provides a method for preventing, controlling or treating diabetes, comprising administering the pharmaceutical composition to a subject.

As used herein, "individual" means a subject in need of a method for preventing, controlling or treating a disease, and more specifically, a primate, mouse, rat, dog, or cat, which is human or non-human. Means mammals, such as horses and cattle.

In addition, the present invention provides a dietary supplement for diabetic improvement comprising chrysanthemum leaf extract as an active ingredient. More specifically, the composition of the present invention may be added to a health functional food for the purpose of preventing or improving diabetes, when using a compound having a prevention or improvement effect of the diabetes of the present invention as a food additive, the compound is added as it is It may be used in combination with other food or food ingredients, and can be appropriately used in accordance with conventional methods. The mixed amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, in the manufacture of food or beverages the compounds of the invention are added in an amount of up to 15% by weight, preferably up to 10% by weight relative to the raw materials. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below 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.

There is no particular limitation on the kind of food. Examples of foods to which the substance may be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, dairy products including other noodles, gum, ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and includes all of the dietary supplements in the conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage. Natural carbohydrates described above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.20 g, preferably about 0.04 to 0.10 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in carbonated drinks. In addition, the composition of the present invention may contain a pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is usually selected in the range of 0.01 to 0.20 parts by weight per 100 parts by weight of the composition of the present invention.

In addition, the present invention comprises a chrysanthemum leaf extract as an active ingredient, a pharmaceutical composition for the treatment or prevention of insulin resistance-related diseases and chrysanthemum leaf extract as an active ingredient, health functional food for the prevention or improvement of insulin resistance-related diseases A composition can be provided. The insulin resistance related disease may be diabetes, fatty liver, or high blood pressure.

Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the following examples.

EXAMPLE

Example 1 Obtaining Chrysanthemum Leaf Extract

Chrysanthemum morifolium Ramat leaf was pulverized for easy extraction, and 70% ethanol was added to 10 kg of chrysanthemum leaves for 2 hours at 65-75 ℃, and the number of extraction was 3 times. The extract was concentrated and spray dried at 120 ° C. and the yield of chrysanthemum leaf extract was calculated to be 17.4%.

Example 2. Experimental Design

In order to evaluate the glycemic control and insulin resistance improving effect of the chrysanthemum leaf extract experiment was designed as shown in FIG. Specifically, four-week-old male C57BL / 6J mice were purchased from Jackson, USA, and reared for one week with Lab chow, and were fed a normal diet group (ND, AIN-76A) and a high-fat diet group (HFD, 45% of calories). ), Divided into chrysanthemum leaf extract low-dose feeding group (CLL, HFD + 1.5% chrysanthemum leaf extract), and chrysanthemum leaf extract high-dose feeding group (CLH, HFD + 2.5% chrysanthemum leaf extract), and then performed the examples. .

Example 3 Analysis of the Effect on Fasting Blood Sugar by Chrysanthemum Leaf Extract

Fasting blood glucose was measured by fasting mice for 12 hours and collecting blood through the tail vein every four weeks during the 16-week breeding period by the method of Example 2.

As a result, as shown in Figure 2, from 12 weeks after the chrysanthemum leaf extract low dose group (CLL) and chrysanthemum leaf extract high dose group (CLH) significantly lower blood sugar than the high-fat diet group (HFD) and overall breeding period It was confirmed to maintain blood glucose levels over time.

Example 4 Analysis of the Effect on the Glucose Tolerance by Chrysanthemum Leaf Extract

In order to measure the change in blood glucose level after the meal, the mice were fasted for 12 hours at week 14 in the breeding method of Example 2, and then 0.5 g / kg of glucose solution was administered intraperitoneally, followed by tails at 0, 30, 90, and 120 minutes, respectively. Blood glucose was measured by intravenous blood collection. Blood Glucose Measurement The blood glucose concentration of each time period was represented based on the blood glucose concentration of 100 minutes.

As a result, as shown in Figure 3, the blood glucose of the chrysanthemum leaf extract feeding group (CLL, CLH) gradually decreased after 60 minutes and 120 minutes after the peak value of 30 minutes after the glucose load, The blood sugar of 120 minutes was significantly lower than that of the high-fat diet group (HFD) and the blood sugar of the chrysanthemum leaf extract high-dose group (CLH) also decreased. From the above, it was confirmed that when the chrysanthemum leaf extract is treated, blood glucose is reduced and glucose tolerance is increased.

Example  5. Plasma Glucose, C-peptide, Insulin Contents by Chrysanthemum Leaf Extract and HOMA Of the effect on FT-IR values

In order to determine the effect of the chrysanthemum leaf extract of the present invention on the plasma glucose content control and insulin resistance improvement of high fat diet-induced diabetic mice, the following experiment was performed.

5-1. Plasma Glucose Content Analysis

Normal diet group (ND), high fat diet group (HFD), chrysanthemum leaf extract low-dose feeding group (CLL), and chrysanthemum leaf extract high-dose feeding group (CLH) mice were bred for 16 weeks, fasted for 12 hours, and fasted blood was collected. The glucose content in plasma was measured by oxidase method.

As a result, as shown in Figure 4a, in the high-fat diet group (HFD) compared to the normal diet group (ND), the plasma glucose content increased rapidly, whereas the chrysanthemum leaf extract low-dose and high-dose feed group (CLL, CLH) In the case of plasma glucose content significantly decreased, it was found that the chrysanthemum leaf extract had an excellent hypoglycemic effect.

5-2. Plasma C-peptide and Insulin Content Analysis

The C-peptide and insulin contents of the plasma collected according to the method of Example 5-1 were measured. The plasma C-peptide and insulin content were measured using a Multiplex detection kit (Bio-Rad, USA).

As a result, as shown in Figure 4b, the high-fat diet group (HFD) compared to the normal diet group (ND) plasma C-peptide and insulin content increased compared to the chrysanthemum leaf extract low and high dose feed group (CLL, CLH) In the case of, the plasma C-peptide and insulin contents were significantly decreased, indicating the effect of improving chrysanthemum secretion function of chrysanthemum leaf extract.

5-3. Insulin Resistance Indicator Comparative Analysis

The plasma glucose and insulin contents measured according to the methods of Examples 5-1 and 5-2 were compared and analyzed for HOMA-IR, which is an index of insulin resistance and sensitivity. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as [fasting insulin (uU / mL) × fasting glucose (mmol / L)] / 22.5.

As a result, as shown in Figures 4c and 4d, in the case of the chrysanthemum leaf extract low dose and chrysanthemum leaf extract high dose feed group (CLL, CLH) according to the present invention, HOMA-IR values significantly compared to the high fat diet group (HFD) Chrysanthemum leaf extract was found to have an excellent effect on improving insulin resistance.

Example 6 Effect Analysis of Liver Tissue Lipid Profiles by Chrysanthemum Leaf Extract

After breeding for 16 weeks in the method of Example 2 and fasting for 12 hours, lipid was extracted from the extracted liver and dried, and the dried lipid residue was dissolved in 1 ml of ethanol. To 200 μl of dissolved lipid solution, Triton X-100 and sodium cholate solution in distilled water were added to emulsify. The total cholesterol and triglyceride contents of liver were measured using Asan enzymatic kits (Asan, Seoul, South Korea), and the free fatty acid content was measured using Wako NEFA kit (Wako Pure Chemical Industries, Osaka, Japan).

As a result, as shown in Figs. 5a and 5b, in the low dose of chrysanthemum leaf extract and high dose of chrysanthemum leaf extract (CLL, CLH), liver cholesterol and triglyceride contents were significantly reduced compared to the high fat diet group (HFD). . In addition, as shown in Figure 5c, chrysanthemum leaf extract in the low dose group (CLL) was confirmed that the liver free fatty acid content significantly reduced compared to the high fat diet group (HFD).

Therefore, the results of the chrysanthemum leaf extract of the present invention was confirmed to improve the overall insulin resistance by regulating blood sugar and insulin secretion and inhibiting fatty liver.

Example  7. According to chrysanthemum extraction method and site By parking Fasting blood sugar , Plasma glucose, insulin content and HOMA -IR impact comparison

7-1. Extract manufacturer

The anti-diabetic effect of the chrysanthemum leaf alcohol extract according to the present invention by comparing and analyzing the anti-diabetic effect of the chrysanthemum leaf alcohol extract of the present invention prepared by the method of Example 1 with the effect of the chrysanthemum flower hot water extract and chrysanthemum methanol extract We tried to verify that is excellent.

To this end, according to the method of Example 1, the chrysanthemum leaf alcohol extract (CLE1) according to the present invention was prepared, and the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3) were prepared by the previously studied method. More specifically, in the case of chrysanthemum flower hot water extract (CLE2), 2 kg of chrysanthemum flower was extracted by hot water at 90 ° C. for 15 minutes, and the chrysanthemum methanol extract was extracted by adding 99.9% methanol (methanol), an extraction solvent, to 48 kg of chrysanthemum outpost for 48 hours at room temperature. It was. The two extracts were concentrated and freeze dried.

7-2. Fasting Blood Sugar Comparative Analysis

To compare the anti-diabetic effects of chrysanthemum leaf alcohol extract (CLE1) according to the present invention, the previously studied chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3), changes in fasting blood glucose by parking were analyzed.

More specifically, as shown in Fig. 6, male C57BL / 6J mice (n = 50) of 4 weeks old were purchased from Jackson, USA, and adapted for 1 week in Lab chow, normal diet group (ND), and high fat diet group ( HFD), chrysanthemum leaf alcohol extract salary group (CLE1, high fat diet + 1.5% chrysanthemum leaf alcohol extract) prepared by the extraction method of the present invention, chrysanthemum flower hot water extract salary group (CLE2, highland) The cats were categorized into 10 groups of + 1.5% chrysanthemum flower hot water extract) and chrysanthemum methanol extract feeding group (CLE3, high-fat diet + 1.5% chrysanthemum methanol extract) for 12 weeks and fed fasting blood sugar at 4 week intervals. Measured.

As a result, as shown in Figure 7, high-fat diet group (HFD) significantly increased fasting blood sugar at 4 weeks of breeding compared to the normal diet group (ND), and extracted with chrysanthemum leaf alcohol extract (CLE1) Chrysanthemum flower hot water extract (CLE2) significantly reduced fasting blood glucose compared to the high fat diet group (HFD). However, the chrysanthemum leaf alcohol extract group (CLE1) of the present invention showed a statistically more significant effect of inhibiting blood glucose increase than the chrysanthemum flower hydrothermal extract group (CLE2). Chrysanthemum leaf alcohol extract (CLE1) according to the present invention in weeks 8 and 12 was found to have an excellent hypoglycemic effect compared to the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3).

7-3. Comparison of Plasma Glucose, Insulin Content and HOMA-IR Levels

Plasma glucose, insulin content and HOMA-IR values were measured and analyzed for the mice of each group bred for 12 weeks by the method of Example 5.

As a result, as shown in Figure 8, the high-fat diet group (HFD) significantly increased plasma glucose, insulin and HOMA-IR levels compared to the normal diet group (ND). On the other hand, in the case of plasma glucose, the chrysanthemum leaf alcohol extract group (CLE1) and the previously studied chrysanthemum flower hot water extract group (CLE2) were significantly reduced than the high-fat diet group (HFD), but the chrysanthemum methanol extract group (CLE3) was There was no significant difference. Plasma insulin and HOMA-IR, an insulin resistance marker, were significantly lower than the high fat diet (HFD) group, but the chrysanthemum leaf alcohol extract group (CLE1) showed the best plasma insulin and HOMA-IR levels. Reduced.

Through the above results, the chrysanthemum leaf alcohol extract (CLE1) according to the present invention, compared to the chrysanthemum flower hot water extract (CLE2) and chrysanthemum methanol extract (CLE3), as well as fasting blood sugar, excellent insulin resistance by reducing the overall antidiabetic The effect was confirmed to be excellent.

Examples of preparations for the compositions of the present invention are illustrated below.

Formulation example  1: Preparation of pharmaceutical preparation

1. Preparation of powder

Chrysanthemum Leaf Extract 200mg

Lactose 100mg

The above ingredients were mixed and filled in airtight cloth to prepare a powder.

2. Preparation of Tablets

Chrysanthemum Leaf Extract 200mg

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

3. Preparation of Capsule

Chrysanthemum Leaf Extract 200mg

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

4. Preparation of Injectables

Chrysanthemum Leaf Extract 200mg

Mannitol 100mg

Na ₂ HPO ₄ 12H ₂ O 2mg

Appropriate sterile distilled water for injection

Injectables were prepared by mixing the above ingredients per ampoule (2 ml) according to the usual method for preparing injectables.

Formulation Example 2 Preparation of Food

Food containing the chrysanthemum leaf extract of the present invention was prepared as follows.

1. Preparation of Cooking Seasonings

Chrysanthemum leaf extract 20-95% by weight was prepared for health promotion cooking seasoning.

2. Preparation of Tomato Ketchup and Sauce

0.2-1.0% by weight of chrysanthemum leaf extract was added to tomato ketchup or sauce to prepare tomato ketchup or sauce for health promotion.

3. Manufacturing of Flour Foods

Chrysanthemum leaf extract 0.5-5.0% by weight was added to the flour, using this mixture to prepare bread, cakes, cookies, crackers and noodles to produce health foods.

4. Preparation of soups and gravy

Chrysanthemum leaf extract 0.1-5.0% by weight was added to soups and gravy to prepare health-promoting meat products, noodle soup and gravy.

5. Preparation of Ground Beef

10% by weight of chrysanthemum leaf extract was added to ground beef to prepare ground beef.

6. Manufacture of Dairy Products

5-10% by weight of chrysanthemum leaf extract was added to milk and various milk products, such as butter and ice cream, were prepared using the milk.

Formulation example  3: preparation of beverages

1. Preparation of Carbonated Drinks

Add 10-15% chrysanthemum leaf extract, 5-10% sugar, 0.05-0.3% citric acid, 0.005-0.02% caramel, 0.1-1% vitamin C, and add 75-80% purified water to the syrup. made. The syrup was sterilized at 85-98 ° C. for 20-180 seconds, mixed with cooling water at a ratio of 1: 4, and 0.5-0.82% of carbon dioxide was injected to prepare a carbonated beverage containing chrysanthemum leaf extract.

2. Manufacture of health drinks

Chrysanthemum leaf extract (2.5% solids, 97.16%), jujube extract (65 brix, 2.67%), overweight extract (solids 70%, 0.12%), vitamin C (0.02%), calcium pantonthenate (0.02%), licorice A homogeneous blend of extracts (65% solids, 0.01% solids) was instantaneously sterilized and then packaged in small packaging containers such as glass bottles and plastic bottles to prepare healthy drinks.

3. Preparation of Vegetable Juice

0.5 g of chrysanthemum leaf extract was added to 1,000 ml of tomato or carrot juice to prepare vegetable juice for health promotion.

4. Preparation of Fruit Juice

0.1 g of chrysanthemum leaf extract was added to 1,000 ml of apple or grape juice to prepare fruit juice for health promotion.

Formulation Example 4 Preparation of Health Functional Food

Chrysanthemum Leaf Extract 200mg

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

Vitamin mixture proper amount

0.2 μg of vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

Folic acid 50 μg

Calcium Pantothenate 0.5 mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

15 mg potassium monophosphate

Dicalcium Phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

After mixing the above components, a health functional food was prepared according to a conventional method.

The description of the present invention set forth above is for illustrative purposes, and one of ordinary skill in the art may understand that the present invention may be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. There will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.

The pharmaceutical composition for preventing or treating diabetes mellitus according to the present invention comprises chrysanthemum leaf extract as an active ingredient, when the chrysanthemum leaf extract is administered to a dietary obesity-induced mouse model, the fasting blood sugar is lowered, and plasma glucose and plasma insulin are reduced. It was confirmed experimentally that the effect of improving insulin resistance, such as lowering and inhibiting the increase of C-peptide content. Accordingly, the chrysanthemum leaf extract is expected to be useful for improving blood sugar and preventing and treating insulin resistance-related diseases, and for preventing or improving insulin resistance-related diseases, which are characterized by controlling blood sugar and insulin secretion. It can also be used as a health functional food composition.

Claims (14)

Chrysanthemum leaf extract as an active ingredient, preventing or treating pharmaceutical composition for diabetes. According to claim 1, wherein the composition is characterized in that lowering blood sugar, pharmaceutical composition for preventing or treating diabetes. According to claim 1, wherein the composition is characterized in that to improve insulin resistance, preventing or treating diabetes pharmaceutical composition. The method of claim 1, wherein the chrysanthemum leaf extract is composed of water, C1 to C4 lower alcohol, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and a mixed solvent thereof A pharmaceutical composition for preventing or treating diabetes, characterized in that extracted with a solvent selected from the group. The method of claim 1, wherein the chrysanthemum leaf extract, characterized in that it comprises 1 to 5% by weight based on the total weight of the composition, a pharmaceutical composition for preventing or treating diabetes. Chrysanthemum leaf extract as an active ingredient, preventing or improving health functional food composition for diabetes. According to claim 6, wherein the composition is characterized in that lowering blood sugar, health functional food composition for preventing or improving diabetes. According to claim 6, wherein the composition is characterized in that to improve insulin resistance, health functional food composition for preventing or improving diabetes. The method of claim 6, wherein the chrysanthemum leaf extract is composed of water, C1 to C4 lower alcohol, n-hexane, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and a mixed solvent thereof A health functional food composition for preventing or improving diabetes, characterized in that extracted with a solvent selected from the group. According to claim 6, The chrysanthemum leaf extract is characterized in that it comprises 1 to 5% by weight based on the total weight of the composition, health functional food composition for the prevention or improvement of diabetes. Chrysanthemum leaf extract as an active ingredient, the composition for the treatment or prevention of insulin resistance-related diseases. Comprising chrysanthemum leaf extract as an active ingredient, a health functional food composition for the prevention or improvement of insulin resistance-related diseases. A method of preventing or treating diabetes, comprising administering to a subject a composition comprising chrysanthemum leaf extract as an active ingredient. Use of the composition comprising chrysanthemum leaf extract as an active ingredient, preventing or treating diabetes.

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