KR20150096276A - Compositions for preventing or treating prediabetes, diabetes mellitus or diabetic complications comprising Rg3, Rutin, or their combination as an active ingredient - Google Patents

Abstract

The present invention relates to a composition including Rg3, rutin, or combination thereof as an active ingredient for preventing or treating prediabetes, diabetes, or diabetic complications. According to the present invention, the composition including Rg3, rutin, or combination thereof promotes secretion of incretin hormone in a human enteroendocrine cell. Therefore, the composition has an effect of decreasing blood sugar caused by inducing secretion of insulin, and thus can be advantageously used for preventing or treating prediabetes, diabetes, or diabetic complications.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing and treating diabetes mellitus, diabetes mellitus or diabetic complications, which comprises Rg3, a rutin or a combination thereof as an active ingredient. an active ingredient}

The present invention relates to a pharmaceutical or food composition comprising Rg3, a routine, or a combination thereof as an active ingredient. Specifically, the present invention relates to a composition comprising Rg3, a rutin, or a combination thereof as an active ingredient, and to prevention, improvement, and treatment of complications due to pre-diabetes, diabetes, and diabetes using the same.

Studies on various degenerative diseases have been progressing actively due to the increase in life expectancy due to improvement of living standard. Of these, diabetes is a rapidly growing trend and is the third most serious disease worldwide. Currently, about 250 million people worldwide are estimated to be diabetic. In Korea, the prevalence and incidence of diabetes mellitus are gradually increasing due to industrial development, economic growth, changes in lifestyle, and aging. Currently, about 3 million to 5 million people are estimated to be diabetic.

Diabetes mellitus is a disease in which glucose present in the blood is excreted through the urine and is one of the chronic degenerative diseases that are not healed. Due to changes in diet and lack of exercise, a major change has occurred in the energy metabolism of the human body, and chronic degenerative diseases such as diabetes are increasing. In Korea, the prevalence of diabetes is known to be 5-10%, and it is continuously increasing. In the United States, over the past 40 years, diabetes has increased sixfold, and by such an increase it is expected that by 2050 the number of patients will reach 26 million.

The etiology of type 2 (non-insulin dependent) diabetes, which accounts for more than 95% of diabetes, is known to be a combination of two causes: insulin secretory disorder and insulin resistance. In other words, diabetes mellitus is a chronic hyperglycemia due to this complex disorder. In particular, non-insulin dependent diabetes mellitus, which usually develops after the age of 40, is regarded as one of the three major adult illnesses.

Insulin secretory disorder refers to a situation in which insulin is not released from the pancreatic beta cells in a proper amount depending on the concentration of glucose. This includes both quantitative reduction of insulin-secreting beta cells and functional distribution disorders. Insulin resistance is a condition in which secreted insulin reaches the target organs in the bloodstream, but the insulin action and sensitivity of the target cells are lowered. It is generally considered to be a signal transduction disorder after cell membrane receptor binding, , Obesity, decreased physical activity, and hyperglycemia or dyslipidemia. Insulin resistance requires that a greater amount of insulin be secreted to overcome resistance, and conversely, insulin secretion is not sufficient to cause insulin resistance to be exacerbated by hyperglycemia itself.

Prediabetes means a high risk group that can go to diabetes due to abnormal blood sugar control that precedes diabetes. Pre-diabetes is 3 to 5 times higher risk for future diabetes than normal people. In addition, although blood sugar is not as high as diabetes, the risk of cardiovascular disease such as stroke and myocardial infarction is 3 to 5 times higher than that of normal people because of increased stress on blood vessels because it is higher than normal people. The former type of diabetes includes impaired fasting lycemia (IFG), impaired glucose tolerance (IGT), and metabolic syndrome.

Currently, diabetes is being treated by dietary therapy, exercise therapy, sulphonylurea, biguanide, α-glucosidase inhibitors, and insulin. Has been developed and applied to clinical practice. However, these therapeutic agents have problems in that they have low efficacy or cause many side effects such as liver dysfunction, hypoglycemia, and lactic acidosis.

Accordingly, there is a need for a diabetic therapeutic agent that reduces adverse effects of existing diabetic therapeutic agents, improves metabolic abnormalities, and is safe even when administered over a long period of time.

Accordingly, the inventors have recognized and studied the need to develop a composition that is effective in preventing, ameliorating, or treating complications due to pre-diabetes mellitus, diabetes mellitus, and diabetes mellitus while minimizing adverse effects and as a result, it has been found that Rg3, Of the present invention accelerates secretion of incretin hormone in human endocrine endocrine cells, and as a result, it is confirmed that there is an effect of lowering blood glucose by induction of insulin secretion, thus completing the present invention.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating effective pre-diabetes, diabetes, or diabetic complications including Rg3, a routine, or a combination thereof as an active ingredient.

It is another object of the present invention to provide a food composition for preventing or ameliorating effective pre-diabetes, diabetes, or complications due to diabetes, comprising a combination of Rg3 and a routine as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for treating or preventing complications due to pre-diabetes, diabetes, or diabetes comprising Rg3, a routine, or a combination thereof as an active ingredient.

The present invention also provides a food composition for preventing or ameliorating complications due to pre-diabetes, diabetes, or diabetes comprising Rg3, a routine, or a combination thereof as an active ingredient.

The composition comprises a pharmaceutical composition or a food composition.

In the present invention, the diabetes may be type 2 diabetes. In addition, the complications due to diabetes include cardiovascular diseases, neuropathy, skin infections, skin symptoms caused by hypersensitivity reaction with sebaceous blood vessel or therapeutic agent, lens opacity and cataract, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy , And the like.

Hereinafter, the present invention will be described in more detail.

All technical terms used in the present invention are used in the sense that they are generally understood by those of ordinary skill in the relevant field of the present invention unless otherwise defined. In addition, preferred methods or samples are described in this specification, but similar or equivalent ones are also included in the scope of the present invention. The contents of all publications referred to in this specification are incorporated herein by reference in their entirety.

The ginsenoside Rg3 used as an active ingredient of the present invention is a fumaran-type saponin having 1-4 saccharides bonded to a dammarane skeleton. The saponin based on the above-mentioned fermion has protopanaxadiol (PPD) as a parent nucleus and can be expressed as shown in Equation (1).

(식1)

(Equation 1)

Depending on R ₁ , R ₂ , and R ₃ in the formula 1, the saponins of the fermane-base can be classified as follows.

group Gin Senocide R ₁ R ₂ R ₃ Protopanax dior Rb1 -Glc-Glc -H -Glc-Glc Rb2 -Glc-Glc -H -Glc-Ara (pyr)

20 (S) -Rg3 or 20 (R) -Rg3 can be generated by the escape of -Glc-Glc or -Glc-Ara (pyr) at position 20 of protopanaxadiol ginsenosides Rb1 and Rb2 have.

The ginsenoside Rg3 may be included in an extract of a plant of the genus Panax . The plant of the Panax genus is called Panax ginseng , Panax quinquefolia), jeonchilsam (thirty-seven, Panax notoginseng , Panax japonica , Panax trifolia , Panax pseudoginseng , or Panax vietnamensis . The plant belonging to the genus Panax contains common saponins of fumaran, which have 1-4 sugars bound to the dammarane skeleton. Said saponin is ginsenoside Rb1, Rb2, Rg3, Rc, Rd, Rg1, or Re.

As used herein, the term " Panax sp. Extract "means a substance obtained by extracting from the root of Panax spp. The extract may be extracted by a conventional extraction solvent known in the art, for example, water, a hydrophilic organic solvent or a mixed solvent thereof. The hydrophilic organic solvent may be an anhydrous or a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, propanol, butanol, n-propanol, isopropanol and n-butanol, acetone, ethyl acetate, chloroform, - butylene glycol, hexane, diethyl ether or butyl acetate. The extract may be a diluent or concentrate of the extract obtained by extraction, a dried product obtained by drying the extract, or a preparation or purified product of the extract.

Rutin is a luteolin glycoside containing the -O-sugar in position 3. Routines are found in eucalyptus leaves or in many flowers. The routine can be expressed as Equation 2:

(식 2)

(Equation 2)

Also, the routine can be synthesized by rutin synthase activity (Lucci et al., Canadian journal of plant science, 89 (5): 895-902, 2009).

The Rg3, the routine, or a combination thereof may be one that promotes secretion of incretin hormone. Incretine is a hormone secreted by the small intestine when it eats food, helping to secrete insulin from the pancreas, and is recently seen as a new alternative to diabetes treatment. The most important advantages of treatment with incretin hormone are that it has few side effects such as hypoglycemia and weight gain, which are the blind points of insulin hormone therapy, and also beta cell of pancreas damaged by diabetes is regenerated, to be. Prior to the development of incretin as a therapeutic agent, the two important pathophysiologies of diabetes were relative insulin secretion deficiency and insulin resistance. Recently, however, three types of incretin dysfunction have been considered as the pathophysiology of type 2 diabetes. Ingestion of incretin is more powerful than that of intravenous injection of glucose, which is known as the incretin effect, and GLP-1 and GIP are typical examples of incretins.

Cells that secrete gastrin, ghrelin, glucose-dependent insulinotropic peptide (GIP), secretin, and cholecystokinin (CCK) may be present in the stomach and proximal small intestine. Glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), peptide YY (peptide YY) and neurotensin neurotensin) may be present. GLP-1 can be made predominantly in the cells of the small intestine, ileum, and large intestine. GLP-1 may be physiologically stimulated in association with foods such as fats and carbohydrates. In addition, GLP-1 acts directly on beta cells of the pancreas, stimulating differentiation and proliferation of cells, and can increase secretion and synthesis of insulin. In addition, the intestinal motility is suppressed and secretion of gastric fluid and pancreatic juice can be suppressed.

The composition of the present invention may be a composition comprising a combination of Rg3 and a routine. The composition may have a molar ratio of Rg to Lutin of from 6.5 to 7.5: 3, 6.6 to 7.4: 3, 6.7 to 7.3: 3, 6.8 to 7.2: 3, 6.9 to 7.1: The molar ratio may be a mole concentration ratio. The molar ratio may be a molar ratio that brings about the synergistic effect of Rg3 and the routine.

The composition of the present invention may further contain one or more known active ingredients having a composition for preventing or treating diabetes mellitus, diabetes mellitus, or diabetes mellitus in combination with a composition comprising Rg3, rutin, or a combination thereof. The pharmaceutical dosage forms of the compositions comprising the Rg3, routines, or combinations thereof of the present invention may be used in the form of their pharmaceutically acceptable salts and may also be used alone or in combination with other pharmaceutically active compounds Can also be used. The composition of the present invention can also be used in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and / or biological response modifiers.

The pharmaceutical composition of the present invention may be formulated for oral or parenteral administration. Formulations for oral administration may be tablets, granules, capsules, powders, or blended formulations. When formulated for oral administration, it may be formulated using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrating agents and surfactants.

Solid preparations for oral administration may be formulated by mixing tablets, pills, powders, granules, capsules, and the like. In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups, and various excipients such as wetting agents, sweetening agents, fragrances and preservatives in addition to commonly used simple diluents such as water and liquid paraffin . Formulations for oral administration may contain about 0.1 to 1000 mg / kg of body weight, 0.1 to 800 mg / kg of body weight, 1 to 500 mg / kg of body weight or 100 to 300 mg / kg of body weight of active ingredient per dosage unit. It may be administered 1 to 6 times a day, 2 to 5 times, or 3 to 4 times a day.

The formulation for parenteral administration may be a formulation for inhalation administration. Formulations for inhalation administration may be in the form of an aerosol formulation with or without a propellant.

The term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the drug form, the administration route and the period, and can be appropriately selected by those skilled in the art. For a desired effect, the composition of the present invention may be administered in an amount of 0.0001 mg / kg to 10000 mg / kg per day. The composition may be administered once a day, or may be administered several times.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery of disease and aging inhibition.

A composition comprising Rg3, a routine, or a combination thereof of the present invention may be added to a health functional food for the purpose of preventing or ameliorating complications due to pre-diabetes, diabetes or diabetes. When a composition comprising Rg3, a routine, or a combination thereof of the present invention is used as a food additive, the composition comprising the Rg3, the rutin, or a combination thereof may be added intact or used together with other food or food ingredients, May be appropriately used depending on the method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). In general, a composition comprising Rg3, a rutin, or a combination thereof of the present invention in the production of a food or beverage is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

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

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Another aspect provides a method of treating complications of pre-diabetes, diabetes, or diabetes using a pharmaceutical composition comprising Rg3, a routine, or a combination thereof according to the disclosure as an active ingredient. The treatment method can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention and treatment of pre-diabetes, diabetes, or diabetes. Rg3, the routine, or a combination thereof. In addition, the complications due to diabetes and diabetes are as described above.

The composition comprising Rg3, a routine, or a combination thereof according to the present invention promotes secretion of incretin hormone in human endocrine endocrine cells, resulting in a blood glucose lowering effect by induction of insulin secretion and is excellent in pre-diabetes, And can be usefully used for preventing or treating complications due to diabetes.

FIG. 1 shows the results of confirming the secretion promoting effect of GLP-1 in NCI-H716 cells, which are human intestinal endocrine cells, of a composition containing Rg3 and a routine. Statistical analysis was performed with Student's t-test. In FIG. 1, BSL represents a positive control group with basal and Q represents a positive control group with 2 mM quinine. ** indicates P <0.01, *** indicates BSL versus P <0.001, # indicates Rg3 alone, Gt; P < 0.05.
2 is a graph showing blood glucose lowering effects of a composition containing Rg3 and a routine in a mouse model of type 2 diabetes.
Figure 3 is a graph showing GLP-1 secretion promoting effects of a composition comprising Rg3 and a routine in a mouse model of type 2 diabetes.
4 is a graph showing the insulin secretion promoting effect of a composition comprising Rg3 and a routine in a mouse model of type 2 diabetes.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  1. Intestinal endocrine cells Rg3 And routine GLP Promote the secretion of -1

1-1. Cell culture and endocrine differentiation ( endocrine differentiation )

Human endocrine cells, NCI-H716, were obtained from Korean Cell Line Bank (KCLB® Seoul, South Korea). Cells were cultured in RPMI 1640 supplemented with 10% fetal bovine serum (FBS; Lonza, Walkersville, MD, USA) and antibiotic-antimycotic solution (Gibco BRL, Grand Island, MD, USA) medium to the appropriate number.

The cells were then plated on Matrigel-precoated plates with Matrigel (BD Bioscience, Bedford, Mass., USA) and incubated with 10% FBS and antibiotic- antimycotic solution was incubated in a CO ₂ incubator for 48 h in Dulbecco's modified Eagle's medium (Lonza, Walkersville, MD, USA) supplemented with DMEM. The medium was then replaced with serum-free DMEM medium and incubated for an additional 12 hours.

1-2. Preparation of Test Materials

Rg3 was purchased from Sigma-Aldrich (St. Louis, MO, USA) and the routine was purchased from santacruz biotechnology (Dallas, TX, USA).

1-3. Treatment of cells with test substances

Humulin enteroendocrine cells were treated with 10 μM Rg3, 10 μM routine, 7 μM Rg3 + 3 μM routine, 5 μM Rg3 + 5 μM routine, and 3 μM Rg3 + 7 μM routines Each was treated and cultured for 1 hour. BSL was treated with 1% DMSO, and Q was treated with 2 mM quinine.

1-4. GLP -1 secretion analysis

GLP-1 secretion was assayed by GLP-1 ELISA. Specifically, the endocrine differentiation cell culture medium was replaced with PBS containing 1 mM CaCl ₂ and a different drug conformation. After incubation for 1 hour in a CO ₂ incubator, the supernatant was collected and centrifuged at 1,000 x g for 10 minutes at 4 ° C. Human GLP-1 multiplex assay (Bio-Rad, Hercules, Calif., USA) was performed according to the user's manual. The GLP-1 concentration in each sample was measured with a Bio-Plex® MAGPIX ™ Multiplex reader (Bio-Rad, Hercules, CA, USA). The results were analyzed with Bio-Plex Manager software (Bio-Rad, Hercules, CA, USA).

Figure 1 shows the results of confirming GLP-1 secretion-promoting effects on NCI-H716 cells, human endocrine cells, of a composition comprising Rg3 alone, rutin alone, and Rg3 and rutin. Q represents the case of treatment with 2 mM quinine. As shown in FIG. 1, the compositions of Rg3 alone, rutin alone, and Rg3 and rutin significantly increased the secretion of GLP-1 in human intestinal endocrine cells compared with the control group, -1 secretion promoting effect.

Also, in the case of a composition comprising Rg3 and a rutin at a molar concentration of 7: 3, compositions comprising Rg3 alone, Rutin alone, Rg3 and rutin in a ratio of 5: 5, and Rg3 and Rutin in a 3: 7 ratio The secretion of GLP-1 was significantly increased in human intestinal endocrine cells compared to the case where the composition was treated. Specifically, when the composition of Rg3 and the rutin ratio of 7: 3 was treated, the secretion of GLP-1 was increased by about 10% more than that of Rg3 alone, and that of GLP-1 Secretion increased by about 24%. Thus, a composition comprising Rg3 and a rutin at a molar concentration ratio of 7: 3 has a synergic effect on promoting GLP-1 secretion in human endocrine endocrine cells, compared with Rg3 and rutin alone Respectively.

Example  2. Identification of blood glucose lowering effect in mouse model

Oral glucose tolerance test (OGTT) was performed to confirm blood glucose lowering effect in mouse model. The oral glucose tolerance test measures the increase in intravenous serum glucose after fasting glucose and is used to diagnose diabetes, impaired glucose tolerance or insulin secretion.

Oral glucose tolerance test was performed using db / db mouse (Leptin receptor knock-out mice) (35g-39g), a type 2 diabetes model. Male 6-week-old db / db mice were purchased from BioLink (DBL, South Korea).

Fasting blood glucose levels of fasting db / db mice fasted for 18 hours were measured. Then, each experimental group, the control group and the positive control group was administered with a composition containing Rg3 and a routine, metformin (Metformin), and physiological saline (saline). A composition containing Rg3 and a routine was administered (30 mg of Rg3 + 90 mg of lutein) / kg and metformin was administered at 300 mg / kg as a positive control. Each group was then orally administrated with 5 g / kg body weight of glucose. Blood samples were collected at 10, 20, 40, 90, and 120 minutes after the administration of glucose and blood glucose level was measured with a blood glucose meter.

2 is a graph showing blood glucose lowering effects of a composition containing Rg3 and a routine in a mouse model of type 2 diabetes. As shown in Fig. 2, the oral administration of the composition containing Rg3 and the rutin has a blood glucose-strengthening effect in the mouse model of type 2 diabetes compared with the physiological saline-administered group, and a blood glucose-strengthening effect similar to that of metformin .

Example  3. In the mouse model GLP Promote the secretion of -1

In order to confirm the insulin secretion promoting effect in the mouse model, oral glucose tolerance test was performed as in Example 2. Specifically, plasma GLP-1 concentrations per hour after oral administration of a composition comprising 30 mg / kg of Rg3 and 90 mg / kg of the routine in a db / db mouse model and 2 g / Kg of glucose were determined. In addition, the group to which physiological saline was administered was used as a control group, and the group to which 300 mg / Kg of metformin was administered was used as a positive control group.

Figure 3 is a graph showing GLP-1 secretion promoting effects of a composition comprising Rg3 and a routine in a mouse model of type 2 diabetes. As shown in Figure 3, a high level of GLP-1 was secreted into mouse plasma after 10 minutes of glucose loading by the composition comprising Rg3 and the routine. Thus, the composition shows an excellent GLP-1 secretion promoting effect as compared with the control group as well as the positive control group.

Example  4. Promoting insulin secretion in mouse models

In order to confirm the insulin secretion promoting effect in the mouse model, oral glucose tolerance test was performed as in Example 2. Specifically, a composition comprising 30 mg / kg of Rg3 and 90 mg / kg of the routine in a db / db mouse model, and 2 g / Kg of glucose were orally administered to confirm plasma insulin levels per hour. In addition, the group to which physiological saline was administered was used as a control group, and the group to which 300 mg / Kg of metformin was administered was used as a positive control group.

4 is a graph showing the insulin secretion promoting effect of a composition comprising Rg3 and a routine in a mouse model of type 2 diabetes. As shown in FIG. 4, a high level of insulin was secreted into mouse plasma after 20 minutes of glucose loading by the composition comprising Rg3 and the routine. Therefore, a composition containing Rg3 and a routine has a GLP-1 secretion promoting effect in the mouse model, and as a result, it exhibits a hypoglycemic effect by inducing insulin secretion. Thus, the composition shows an excellent insulin secretion promoting effect as compared with the control and the positive control.

Hereinafter, a pharmaceutical composition containing the composition of the present invention and an example of a preparation for a health functional food will be described, but the present invention is not intended to be limited but is specifically described.

Formulation example  1. Preparation of Pharmaceutical Compositions

1-1. Sanje  Produce

Composition of Rg3 and Routine 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

1-2. Manufacture of tablets

Composition of Rg3 and Routine 10 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

1-3. Preparation of capsules

Composition of Rg3 and Routine 10 mg

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

1-4. Injection preparation

Composition of Rg3 and Routine 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

1-5. Liquid  Produce

Composition of Rg3 and Routine 10 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation example  2. Formulation of food composition

2-1. Manufacture of health food

Composition of Rg3 and Routine 100 mg

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 [mu] g vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2-2. Health drink  Produce

Composition of Rg3 and Routine 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3 g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered to obtain a sterilized container, which was sealed and sterilized, Used in the manufacture of health beverage compositions.

Although the composition ratio of the ingredients suitable for the beverage is comparatively low, it is also possible to arbitrarily modify the blending ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

The present invention was carried out under the research project of the Korea Science and Technology Foundation.

Claims (9)

A pharmaceutical composition for the treatment or prevention of pre-diabetes mellitus, diabetes mellitus, or complications resulting from diabetes, comprising Rg3, a routine, or a combination thereof as an active ingredient. 4. The composition of claim 1, wherein the Rg3, the routine, or a combination thereof promotes secretion of incretin hormone. The composition according to claim 1, wherein the diabetes is type 2 diabetes. The method according to claim 1, wherein the complication due to diabetes is cardiovascular disease, neuropathy, skin infection, skin symptom caused by hypersensitivity reaction with sebaceous or therapeutic agent, lens opacity and cataract, diabetic retinopathy, diabetic nephropathy and diabetes Neuropathy, neuropathy, and neuropathy. The composition of claim 1, wherein the molar ratio of Rg3: Routine is 6.5 to 7.5: 3. The pharmaceutical composition according to claim 1, which is a formulation for oral administration, a formulation for inhalation administration, or a preparation for injection. The pharmaceutical composition according to claim 1, comprising 0.1 to 1000 mg / kg body weight per dosage unit. The pharmaceutical composition according to claim 1, which is a tablet, granule, capsule or powder. Rg3, a routine, or a combination thereof as an active ingredient.

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