KR101989739B1 - Composition for preventing or treating diabetes mellitus comprising Rorippa globosa extracts - Google Patents

Abstract

The present invention provides a composition for preventing, alleviating or treating diabetes containing a Rorippa globose extract. The composition according to the present invention significantly lowers the level of insulin in a hyperinsulinemic state and prevents the outbreak of insulin resistance, thereby exhibiting an excellent effect of preventing and treating diabetes and hyperinsulinemia. Therefore, the composition can be usefully used as a pharmaceutical composition or a health functional food.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention or treatment of diabetes mellitus comprising Ralippa globosa extracts as an active ingredient,

The present invention relates to a process for the preparation of beads, globosa extract of the present invention for preventing or treating diabetes.

Diabetes is a type of metabolic disease caused by the abnormal action of insulin. It is characterized by hyperglycemia in which the concentration of glucose in the blood increases. Hyperglycemia causes various symptoms and signs and discharges glucose from the urine.

Diabetes is divided into type 1 and type 2, type 1 diabetes occurs due to insulin production, type 2 diabetes, insulin secretion, insulin function, but the cells lose insulin resistance (insulin resistance) . For example, insulin resistance is caused by hyperinsulinemia, which is higher than the normal amount of insulin in the blood, and thus, due to the mechanism of action to make up more insulin, hyperinsulinemia leads to type 2 diabetes It may develop. In addition, hyperinsulinemia as described above has a high level of insulin in the blood, and has an additional problem of promoting sympathetic hyperactivity or sodium absorption in the kidney.

As a substance for treating type 2 diabetes, PPAR-gamma activator, GLP-1 derivative, DPP-IV inhibitor and PTP1B inhibitor have been developed as major diabetes medicines, but these conventional medicines have side effects due to respective mechanisms have. For example, toxicity to the liver, kidney, muscle and heart as well as weight gain symptoms are typical side effects. In particular, when sulfonylurea and biguanide preparations, which are mainly used as oral hypoglycemic agents, are administered, the blood sugar level increases rapidly after eating, while the blood of insulin due to the administered drug The occurrence of hyperinsulinemia can not be solved between postprandial hyperglycemia, meals and meals because of its relatively slow appearance.

Under these circumstances, research and development of compositions for preventing, improving or treating diabetes and hyperinsulinemia using natural materials that can be easily used as food or pharmaceutical materials are urgently needed.

Korean Patent Application No. 10-1679117 Korean Patent Application No. 10-1095467

The present invention provides a pharmaceutical composition for preventing or treating diabetes comprising Rorippa globosa extract as an active ingredient.

The present invention also provides a pharmaceutical composition for preventing or treating hyperinsulinemia comprising Rorippa globosa extract as an active ingredient.

In addition, the present invention provides a food composition for preventing or improving diabetes comprising Rorippa globosa extract.

The present invention also provides a food composition for preventing or ameliorating hyperinsulinemia comprising Rorippa globosa extract as an active ingredient.

The present inventors have made intensive efforts to find substances capable of preventing, ameliorating, and treating diabetes in natural plant materials having excellent safety. As a result, surprisingly, it has been found that Rorippa globosa extract is effective against diabetes, especially diabetes associated with hyperinsulinemia And the present invention has been completed.

The present invention provides a pharmaceutical composition for preventing or treating diabetes comprising Rorippa globosa extract as an active ingredient.

The pharmaceutical composition for preventing or treating diabetes according to the present invention exhibits excellent effects in the prevention and treatment of diabetes by significantly lowering the level of insulin in a hyperinsulinemic state.

In the present invention, "diabetes" is a disease caused by an abnormal action of insulin. In the present invention, diabetes includes all kinds of diabetes, including, for example, type 1 diabetes or type 2 diabetes. Preferably, the diabetes that is prevented or treated by the composition of the present invention is type 2 diabetes. More preferably, the diabetes that is prevented or cured by the composition of the present invention is type 2 diabetes caused by hyperinsulinemia or type 2 diabetes caused by insulin resistance.

Type 2 diabetes can be caused by insulin resistance due to hyperinsulinemia, which maintains high levels of insulin in the blood. The composition according to the present invention exhibits excellent effects on type 2 diabetes by significantly lowering the blood insulin concentration in the hyperinsulinemic state.

Rorippa globosa is a Rorippa plant with a height of about 60 cm that grows at the foot of a mountain or stream. It is mainly distributed in Chungcheongbuk-do, Chungcheongnam-do, Gyeongsangbuk-do, and Gyeongsangnam-do in Korea.

The extraction site of Rorippa globosa can be extracted without being restricted to plant parts such as flowers, outposts, leaves, stems, seeds, fruits and roots.

The term "extract " of the present invention means an extract obtained by extracting the flowers, outposts, leaves, stems, seeds, fruits, roots or their pulverized products of the beads, the diluted solution or concentrate of the extract, Extracts of all the formulations which can be formed using the extract itself and the extract, such as the obtained dried product, the adjusted product or the purified product of the extracted solution, or a mixture thereof.

The Rorippa globosa extract may be prepared from Rorippa globosa according to a conventional method for preparing an extract. For example, about 1 to 20 times, preferably about 3 to 10 times, the primary extraction solvent, preferably water, of a C ₁ to C ₄ lower alcohol (such as, for example, water) is added to the weight of Rorippa globosa , Methanol, ethanol, propanol, isopropanol, butanol, etc.) or a mixed solvent thereof. Extraction can be carried out by methods known in the art such as, for example, cold-pressing, hot water extraction, ultrasonic extraction, reflux-cooling extraction, and the like. The extraction temperature can be varied by a person skilled in the art in a variety of temperature ranges suitable for the extraction method, for example, but not limited to, from 20 캜 to 100 캜. Further, the extraction time differs depending on the extraction method, and a person skilled in the art can adopt an appropriate extraction time, but can be performed in a single or multiple cycles in a range of about 1 hour to 10 days, although not limited thereto. The extract obtained by performing the extraction with the primary extraction solvent may be obtained in the form of a liquid in which impurities are removed by filtration according to a conventional method, or the obtained liquid form extract may be concentrated under reduced pressure and / Can be obtained.

The extraction step may further include, if necessary, obtaining a fraction having a high active ingredient content. That is, the step of dispersing the extract obtained by extracting with the primary extraction solvent into water and then extracting with an appropriate secondary extraction solvent, for example, an alcohol of water saturated C ₁ -C ₄ is carried out to increase the content of the active ingredient .

According to one embodiment of the present invention, aqueous extracts of Rorippa globosa ethanol were collected from the Nakdong River area. Specifically, the outgrowth of Rorippa globosa was prepared by extracting from 70% (v / v) ethanol extract at 80 ° C for 1 hour.

As used herein, the term "prophylactic " means any act that inhibits or delays diabetes by administering the composition of the present invention to an individual.

The term "treatment ", as used herein, refers to any act that allows the composition of the present invention to be administered to an individual in order to improve or improve diabetes symptoms.

It is preferable but not limited to include Rorippa globosa extract in an amount of 0.1 to 95% by weight based on the total weight of the composition containing the extract of Rorippa globosa of the present invention as an active ingredient.

The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier and may be in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, Can be formulated in the form of sterile injectable solutions.

Such pharmaceutically acceptable carriers may be those conventionally used in the art such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, But are not limited to, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, the pharmaceutical composition of the present invention includes diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants, and other pharmaceutically acceptable additives.

When the pharmaceutical composition of the present invention is formulated into a solid preparation for oral use, it includes tablets, pills, powders, granules, capsules and the like. Such a solid preparation may contain at least one excipient such as starch, calcium carbonate, Sucrose or lactose, gelatin, and the like, including, but not limited to, lubricants such as magnesium stearate, talc, and the like.

When the pharmaceutical composition of the present invention is formulated orally for oral use, it includes suspensions, solutions, emulsions, syrups and the like, and includes, but is not limited to, diluents such as water and liquid paraffin, wetting agents, sweeteners, fragrances and preservatives.

When the pharmaceutical composition of the present invention is formulated for parenteral use, it may contain a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, a lyophilized preparation and a suppository. Examples of the non-aqueous solvent include propylene glycol, polyethylene glycol, Vegetable oils such as oils, injectable esters such as ethyl oleate, and the like. Examples of suppositories include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The dose of the Rorippa globosa extract contained in the pharmaceutical composition of the present invention varies depending on the condition and body weight of the patient, the age, the degree of disease, the drug form, the route of administration and the period of time, . For example, the extract of Rorippa globosa may be administered at a dose of 0.0001 to 100 mg / kg per day, preferably 0.001 to 10 mg / kg per day, You may.

The pharmaceutical composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like by various routes, for example, oral, intraperitoneal or intravenous, muscular, subcutaneous, intrauterine, .

The present invention also provides a pharmaceutical composition for preventing or treating hyperinsulinemia comprising Rorippa globosa extract as an active ingredient.

Hyperinsulinemia is a condition that maintains a high level of insulin levels in the blood, which promotes sympathetic hyperactivity and increases sodium uptake in the kidneys and can cause insulin resistance.

The composition according to the present invention shows a superior effect in the prevention and treatment of hyperinsulinemia by significantly lowering the level of blood insulin.

The term " Rorippa globosa extract ","prevention"," treatment ", and "administration" and the like are the same as described above in the present invention.

The present invention also includes a food composition for preventing or improving diabetes comprising Rorippa globosa extract as an active ingredient.

The food composition of the present invention can be used as a health functional food. The term "functional food" as used herein means a food produced or processed by using raw materials or ingredients having functionality useful to the human body according to the Act on Health Functional Foods, and "functional" refers to the structure and functions of the human body Means taking nutrients for the purpose of obtaining a beneficial effect for health use such as controlling nutrients or physiological action.

The food composition of the present invention may contain conventional food additives, and the suitability of the term "food additives" as referred to above is to be determined by the Food and Drug Administration according to the General Rules and General Test Methods approved by the Food and Drug Administration It shall be judged according to standards and standards for items.

Examples of the substances found in the above-mentioned "food additives" include natural compounds such as ketones, chemical compounds such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring pigments, licorice extracts, crystalline cellulose, high- L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar pigment preparations and the like.

The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight, of Rorippa globosa extract relative to the total weight of the composition. The Rorippa globosa extract contained in the food composition of the present invention can be obtained in the same manner as the extraction method mentioned in the production of the above pharmaceutical composition.

In addition, the food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and circles for the purpose of preventing and / or improving diabetes mellitus.

For example, the health functional food in tablet form may be prepared by granulating a mixture of Rorippa globosa extract, excipient, binder, disintegrant, and other additives in a conventional manner, and then adding a lubricant, etc., Or the mixture can be directly compression molded. The health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.

A hard capsule in a capsule form of health functional food can be prepared by filling a conventional hard capsule with a mixture with an additive such as an extract of Rorippa globosa and an excipient or a granular material or a granular material, The soft capsule can be prepared by filling a capsule base such as gelatin with a mixture of additives such as Rorippa globosa extract and excipients. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The ring-shaped health functional food was Rorippa globosa extract, excipient, binder, disintegrant and the like may be formulated by a suitable method. If necessary, the mixture may be converted into white sugar or other suitable skin care agent, or starch, talc or a suitable substance.

The granular health functional food may be prepared by granulating a mixture of Rorippa globosa extract, excipient, binder, disintegrant and the like in an appropriate manner, and may contain a flavoring agent, a mating agent and the like if necessary . In the granular form of health functional foods, when the next granularity test was carried out using the No. 12 (1680 μm), No. 14 (1410 μm) and No. 45 (350 μm) sieve, the total amount of the 12- 5.0% or less and that passing through the 45-well body may be 15.0% or less of the total amount.

The definitions of the above excipients, binders, disintegrants, lubricants, mating agents, flavoring agents, and the like are described in documents known in the art and include the same or similar functions (Korean Pharmacopoeia, College of Pharmacy, 5th ed., P. 33-48, 1989).

There is no particular limitation on the kind of the food. Examples of foods to which the extract of the present invention can be added include beverages, gums, vitamin complexes, and drinks, and include all health functional foods in a conventional sense.

The present invention provides a food composition for preventing or ameliorating hyperinsulinemia comprising Rorippa globosa extract as an active ingredient.

The term " Rorippa globosa extract "," hyperinsulinemia ", and the like are the same as those described above in the present invention.

The present invention provides a method of treating diabetes comprising administering to a subject an extract of Rorippa globosa .

The term " Rorippa globosa extract "," diabetes ", and "administration" and the like are the same as those described above in the present invention.

The subject refers to an animal and can typically be a mammal capable of exhibiting beneficial effects in treatment with the Rorippa globosa extract of the present invention. A preferred example of such a subject may include primates such as humans. Such subjects may also include all subjects with or at risk of having diabetes symptoms.

The present invention also provides the use of said Rorippa globosa extract in the manufacture of a medicament for the treatment of diabetes.

The present invention also provides a composition comprising said Rorippa globosa extract for use in the treatment of diabetes.

The present invention also relates to a method for the treatment of diabetic rheumatoid arthritis, globosa extract.

The extract of Rorippa globosa according to the present invention significantly reduces the level of insulin in the hyperinsulinemic state and prevents the onset of insulin resistance, thereby exhibiting an excellent effect in the prevention and treatment of diabetes and hyperinsulinemia, As shown in FIG.

FIG. 1 shows the results of confirming the prevention, treatment, and improvement of diabetes and hyperinsulinemia induced by administration of the extract of Rorippa globosa in a insulin-induced diabetic zebrafish model.

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

Example 1: Rorippa globosa ) Preparation of extract

The extracts of beads from Ganoderma lucidum ( Rorippa globosa Hayek) extracted from the Nakdong River basin with 70% ethanol were purchased from National Biological Resources Bank of National Nakdong River.

Example 2. Confirmation of the antidiabetic effect of beads on the insulin-induced diabetic zebrafish

Three days post-fertilization zebrafish larvae were placed in 6 wells and exposed to 10 μM insulin for 48 hours. After exposure to 0.03% seawater salt solution for 24 hours, 1 μg / mL of bean curd extract was exposed for 24 hours. Fluorescence microscopy (Olympus 1 ㅧ 70, Olympus, Japan) was used for direct pancreatic islet observation and stained with 40 μM 2-NBDG for 30 min before fluorescence microscopy. Images obtained through fluorescence microscopy were analyzed for pancreatic islet size in zebrafish using Focus Lite software.

The results are shown in Fig.

FIG. 1 (A) is a graph showing changes in the size of the pancreatic islets, and FIG. 1 (B) shows microscopic photographs thereof.

As shown in Fig. 1, it was confirmed that the pancreatic islet size was significantly increased as compared with the untreated control group due to the treatment of bean curd refuse extract. This shows that the bead extract of the present invention normalizes insulin secretion in the state of excessive insulin secretion, reduces insulin resistance and shows therapeutic effect on hyperinsulinemia, and has an excellent prevention, improvement and therapeutic effect on diabetes .

[Formulation Example]

The following formulation was prepared using the Rorippa globosa extract of Example 1: < tb >< TABLE > However, the following formulation examples are illustrative of the present invention, and the contents of the present invention are not limited thereto.

Preparation Example 1. Preparation of tablets

Rorippa beads globosa extract ... 1000 mg

Lactose ................................................. .... 100 mg

Starch ................................................. .... 100 mg

Magnesium stearate ........................................ Amount

The above components were mixed and tableted according to a conventional tablet preparation method to prepare tablets.

Formulation Example 2. Preparation of a liquid preparation

Rorippa beads globosa extract ... 1000 mg

CMC-Na ............................................... ....... 20 g

Isolation Party ................................................ .... 20 g

Lemon flavor ................................................ ......

Purified water was added to adjust the total volume to 1000 ml. The above components were mixed according to a conventional method for producing a liquid agent, and then filled in a brown bottle and sterilized to prepare a liquid agent.

Formulation Example 3. Preparation of capsules

Rorippa beads globosa extract ... 1000 mg

Crystalline cellulose ................................... 3 mg

Lactose ................................................. 14.8 mg

Magnesium Stearate ...................................... 0.2 mg

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

Formulation Example 4. Preparation of injection

Rorippa beads globosa extract ... 1000 mg

Mannitol ................................................. ... 180 mg

Sterile sterilized distilled water for injection ....................................... 2974 mg

Na ₂ HPO ₄ 12H ₂ O ........................................... ..... 26 mg

(2 ml) per ampoule according to the usual injection preparation method.

Formulation Example 5. Preparation of Health Functional Drink

Rorippa beads globosa ) extract .......................... 100 mg

Citric acid ................................................. ..... 1000 mg

oligosaccharide ................................................. ... 100 g

Plum concentrate ................................................ ..... 2 g

Add purified water to the whole ........................................ 900 mL

The health functional beverage was prepared by mixing the above components according to a conventional health functional drink manufacturing method.

Claims (10)

A pharmaceutical composition for preventing or treating diabetes comprising Rorippa globosa extract as an active ingredient. The pharmaceutical composition according to claim 1, wherein the diabetes is type 1 diabetes or type 2 diabetes. The pharmaceutical composition according to claim 2, wherein the type 2 diabetes is type 2 diabetes induced by hyperinsulinemia or type 2 diabetes induced by insulin resistance. The pharmaceutical composition according to any one of claims 1 to 3, wherein the Rorippa globosa extract is a pharmaceutical composition for preventing or treating diabetes, which is an extract of water, a C ₁ to C ₄ lower alcohol or a mixed solvent thereof . A pharmaceutical composition for preventing or treating hyperinsulinemia comprising Rorippa globosa extract as an active ingredient. A food composition for preventing or improving diabetes comprising Rorippa globosa extract as an active ingredient. The food composition according to claim 6, wherein the diabetes is type 1 diabetes or type 2 diabetes. The food composition according to claim 6, wherein the type 2 diabetes is type 2 diabetes caused by hyperinsulinemia or type 2 diabetes induced by insulin resistance. The composition of any one of claims 6 to 8, wherein the Rorippa globosa extract is an extract of water, a C ₁ to C ₄ lower alcohol or a mixed solvent thereof, which is a food composition for preventing or improving diabetes mellitus . Rorippa beads globosa extract as an active ingredient for preventing or ameliorating hyperinsulinemia.

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