KR20220122299A - Composition for the prevention or treatment of diabetes comprising the extract or a fraction thereof - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating diabetes, a food composition, a health functional food composition, and a method for treating diabetes comprising the step of administering the pharmaceutical composition, which comprises an extract or a fraction thereof as an active ingredient .
The composition comprising the extract or a fraction thereof of the present invention can be widely used for preventing or treating diabetes as it can be administered orally while reducing the main symptoms of hyperglycemia or diabetes.

Description

A composition for preventing or treating diabetes comprising an extract or a fraction thereof, comprising an extract of sorijaegi (Composition for preventing or treating diabetes comprising extract of Rumex crispus or a fraction thereof)

The present invention relates to a pharmaceutical composition for preventing or treating diabetes, a food composition, a health functional food composition, and a method for treating diabetes comprising the step of administering the pharmaceutical composition, which comprises an extract or a fraction thereof as an active ingredient .

Diabetes mellitus (糖尿病, diabetes mellitus) is a representative chronic metabolic disease in which glucose is excreted in the urine due to an increase in blood sugar level due to an abnormal action of insulin. Diabetes mellitus is classified into type 1 diabetes (insulin-dependent diabetes mellitus) and type 2 diabetes (non-insulin-dependent diabetes mellitus) according to the pathogenesis, and type 2 diabetes accounts for more than 95% of all diabetic patients. Type 1 diabetes is mainly caused by an autoimmune process that destroys pancreatic beta cells, and is characterized by insufficient or complete insulin secretion. Type 2 diabetes is caused by interactions such as insulin resistance, decreased beta cell function, and genetic predisposition. In order to overcome insulin resistance, insulin secretion increases, but when it exceeds a certain limit, it cannot increase any more, resulting in high blood sugar and the development of diabetes. Currently, oral hypoglycemic agents used in patients with type 1 and type 2 diabetes include α-glucosidase inhibitors, sulfonylurea agents, and dipeptidyl-peptidase 4 (DPP4) inhibitors. Specifically, there are α-glucosidase inhibitors that delay the absorption of carbohydrates in the small intestine to prevent a rapid rise in postprandial blood glucose levels, and sulfonylurea that promotes insulin secretion from beta cells of the pancreas. In addition, there is a DPP4 inhibitor that selectively inhibits the DPP4 enzyme that directly decomposes the incretin enzyme, which promotes insulin secretion and lowers blood sugar, so that the incretin enzyme is maintained at a high concentration for a long time. Diabetes drugs such as α-glucosidase inhibitors used in clinical practice may exhibit side effects such as abdominal distension, vomiting, and diarrhea in some patients when taken for a long time, so their use may be limited. Until now, a cure method for diabetes has not been established, and there are many restrictions on the use of drugs due to the side effects of drug treatment, so studies to search for a therapeutic agent for diabetes from natural products are being actively conducted.

On the other hand, sorijae ( Rumex crispus ), also called a rustic, is a plant of the genus Soridae, which is native to northern Europe but is distributed around the world. It grows near wetlands, the young leaves are eaten as herbs, and the roots are used as medicine. In addition, it is known that it has been used as a folk remedy for symptoms such as constipation, enteritis, and indigestion, and it has been reported about its antibacterial activity or anti-inflammatory effect on the flora of the skin (Journal of the Korean Dermatological Society, Vol. 9, No. 2). has not been studied at all on its efficacy in treating diabetes.

Under this background, the present inventors completed the present invention by confirming that as a result of intensive research efforts to develop a method for improving and treating diabetes by using a natural product that is safer than synthetic drugs, the extract of Sorijai extract exhibits the effect of treating diabetes. did.

An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of diabetes comprising the extract or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a method for treating diabetes, comprising administering the pharmaceutical composition to a subject in need thereof.

Another object of the present invention is to provide a food composition for the prevention or improvement of diabetes comprising the extract or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a health functional food composition for the prevention or improvement of diabetes comprising the extract or a fraction thereof as an active ingredient.

This will be described in detail as follows. On the other hand, each description and embodiment disclosed in the present invention may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be considered that the scope of the present invention is limited by the specific descriptions described below.

In addition, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Also, such equivalents are intended to be encompassed by the present invention.

One aspect of the present invention for achieving the above object provides a pharmaceutical composition for the prevention or treatment of diabetes comprising an extract or a fraction thereof as an active ingredient.

" Rumex crispus " of the present invention is a perennial plant of the order Rumex crispus, and is also called a pine needle. Regarding the pharmaceutical efficacy of Sorijai, it has been used in oriental medicine for symptoms such as constipation, enteritis, and indigestion. Therefore, in the present invention, it was first identified that the extract of Sorijabi has a therapeutic effect on diabetes.

Sorijae extract of the present invention may be a root extract of Sorijagi, but is not limited thereto.

The sorijae of the present invention may be a raw material, a dried product, or a processed product, and may be purchased and used commercially sold, or collected or cultivated in nature, or received for sale from a depository institution, etc. not limited

As used herein, the term "extract" refers to a liquid component obtained by immersing a target substance in various solvents and then extracting it for a certain period of time at room temperature or in a heated state, and a solid obtained by removing the solvent from the liquid component. it means. In addition, it can be comprehensively interpreted as including all of the dilutions of the above results, their concentrates, their preparations, and their purified products. Accordingly, the extract provided by the present invention includes extracts of all formulations that can be formed using the extract itself and the extract, such as an extract obtained by extracting the extract, a purified product obtained by enzymatic decomposition of the extract, or a mixture thereof. can be interpreted as including

The method of extracting the sound japonica of the present invention is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, reflux extraction, and the like, and these may be performed alone or in combination of two or more methods.

In the present invention, the type of solvent used for the extraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water, alcohol, or a mixed solvent thereof, and these may be used alone or in combination of two or more. 4 alcohols can be used. Specifically, it may be to use 70% ethanol, but is not limited thereto.

As used herein, the term "fraction" refers to a result obtained by performing fractionation in order to separate a specific component or a specific group of components from a mixture including various components.

The fractionation method for obtaining the fraction in the present invention is not particularly limited, and may be performed according to a method commonly used in the art. Non-limiting examples of the fractionation method include a fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing an ultrafiltration membrane having a constant molecular weight cut-off value, and various chromatography (size, charge, hydrophobicity or chromatographic fractionation method for performing separation according to affinity), and combinations thereof. Specifically, there may be mentioned a method of obtaining a fraction from the extract by treating the extract obtained by extracting the sori of the present invention with a predetermined solvent.

In the present invention, the type of the fractionation solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvent include polar solvents such as water and alcohols having 1 to 4 carbon atoms; hexane (Hexan), ethyl acetate (Ethyl acetate), chloroform (Chloroform), a non-polar solvent such as dichloromethane (Dichloromethane); or a mixed solvent thereof. These may be used alone or in combination of one or more, but are not limited thereto, and specifically, hexane, ethyl acetate, butanol, or water may be used alone or in combination of one or more, but limited thereto it's not going to be

In addition, the extract or fraction may be prepared and used in the form of a dry powder after extraction, but is not limited thereto.

"Diabetes" of the present invention means a disease that occurs when the secretion of insulin is insufficient or the action and function of insulin are not sufficiently achieved. Specifically, excessive decomposition of glycogen, protein and lipids causes an abnormal increase in the concentration of glucose in the liver or blood, leading to diabetes and ketonuria. It can lead to pathological conditions such as kidney failure. Insulin is secreted from the β-cells of the pancreatic islet present in the pancreas when the blood glucose concentration increases, and when the blood glucose concentration decreases, the secretion is suppressed, thereby regulating the proper activity of the energy source. Diabetes is generally possible through measurement of blood glucose concentration. In humans, diabetes is generally diagnosed when blood glucose is usually 200 mg/dl or more and 140 mg/dl or more when fasting. Therefore, it can be usefully used for the treatment or prevention of diabetes by restoring damaged pancreatic β-cells or increasing glucose uptake in pancreatic islet cells.

In the present invention, the diabetes may be type 1 diabetes or type 2 diabetes, and the terms “diabetes” or “diabetes” may be used interchangeably.

In a specific embodiment of the present invention, when the sorijae extract was treated on diabetic zebrafish, the effect of increasing the pancreatic islet size was confirmed (Example 2), and it was confirmed that the soritari extract was effective in improving diabetes. .

As used herein, the term "prevention" refers to any act of inhibiting or delaying the occurrence of diabetes using a composition comprising the extract or a fraction thereof as an active ingredient.

As used herein, the term "treatment" refers to any act of treating or improving the symptoms of diabetes using a composition comprising the extract or a fraction thereof as an active ingredient.

The "pharmaceutical composition" of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent. Such pharmaceutically acceptable carriers, excipients, or diluents may be non-naturally occurring. Specifically, the composition is formulated in the form of powders, granules, tablets, liquids, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively. can be used In the present invention, carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate , calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract and its fractions, for example, starch, calcium carbonate, It is prepared by mixing sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to simple diluents such as water and liquid paraffin, which are commonly used for suspensions, solutions, emulsions, and syrups. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

Another aspect of the present invention provides a method for treating diabetes, comprising administering the pharmaceutical composition to an individual in need thereof.

The "pharmaceutical composition", "diabetes", and "treatment" are the same as described above.

As used herein, the term “individual” may refer to any animal, including humans, that has or is likely to develop diabetes. The animal may be a mammal, such as a cow, a horse, a sheep, a pig, a goat, a camel, an antelope, a dog, a cat, and the like, in need of treatment for symptoms similar to those of a human, but is not limited thereto. The subject in need of the composition of the present invention may be a human or non-human subject, but is not limited thereto.

Specifically, the prevention or treatment method of the present invention may include administering the composition in a pharmaceutically effective amount to an individual who has or is at risk of developing diabetes.

As used herein, the term "administration" means introducing the pharmaceutical composition of the present invention to a patient by any suitable method, and the administration route of the composition of the present invention is oral or parenteral as long as it can reach the target tissue. It can be administered through various routes. Specifically, it may be a method of oral administration, but is not limited thereto.

The active ingredient of the pharmaceutical composition of the present invention may vary depending on the age, sex, weight, pathological condition and severity of the subject to be administered, the route of administration, or the judgment of the prescriber. Determination of the amount to be applied based on these factors is within the level of those skilled in the art, and the frequency of administration of the composition of the present invention is not particularly limited thereto, but may be administered once a day or administered several times in divided doses. The above dosage does not limit the scope of the present invention in any way.

Another aspect of the present invention provides a food composition for the prevention or improvement of diabetes comprising the extract or a fraction thereof as an active ingredient.

Another aspect of the present invention provides a health functional food composition for the prevention or improvement of diabetes comprising the extract or a fraction thereof as an active ingredient.

The "Sorijae extract or a fraction thereof", "diabetes" and "prevention" are the same as described above.

As used herein, the term “improvement” refers to any action in which symptoms of suspected and onset individuals are improved or beneficial by using the composition.

As used herein, the term "food" refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, It includes all foods in the usual sense, such as vitamin complexes and health functional foods, and is not limited thereto, as long as it can contain the extract of the present invention or a fraction thereof. In addition, the extract according to the present invention or a fraction thereof can be added to juice, tea, jelly, juice, etc. prepared with the main ingredient, and includes the form of pills, powders, granules, needles, tablets, capsules or liquids. can do.

When the food composition is prepared, it can be prepared by adding raw materials and components commonly added in the art, and the type is not particularly limited. For example, it may include, as an additional ingredient, various herbal extracts, food-logically acceptable food supplements or natural carbohydrates, such as conventional food, but is not limited thereto. The mixing amount of the active ingredient may be suitably determined according to the purpose of use, and since the composition of the present invention uses an extract derived from a natural product as an active ingredient, there is no problem in terms of safety, so there is no major limitation on the mixing amount.

The term "health functional food" of the present invention is the same term as food for special health use (FoSHU), and for the purpose of health supplementation, specific ingredients are used as raw materials or specific ingredients contained in food raw materials are extracted and concentrated. It refers to food manufactured and processed by methods such as , refining, and mixing. It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, regulation of biological rhythm, prevention and recovery of disease, etc., with the above ingredients, and the composition for health functional food is used to prevent disease and disease. It can perform functions related to recovery, etc. The health functional food of the present invention may be used interchangeably with terms known in the art, such as functional food.

Another aspect of the present invention provides for the prevention or treatment of diabetes mellitus extract or a fraction thereof or a composition comprising the same.

Another aspect of the present invention provides a use for preparing a medicament for the prevention or treatment of diabetes mellitus of an extract or a fraction thereof or a composition comprising the same.

The "Sorijae extract or a fraction thereof", "diabetes" and "prevention" are the same as described above.

The composition comprising the extract or a fraction thereof of the present invention can be widely used for preventing or treating diabetes as it can be administered orally while reducing the main symptoms of hyperglycemia or diabetes.

1 is a fluorescence micrograph showing the result of treatment with a diabetic zebrafish extract and a graph showing the change in the size of pancreatic islets calculated from the fluorescence micrograph.

Hereinafter, the present invention will be described in more detail through examples. These Examples are for explaining the present invention in more detail, and the scope of the present invention is not limited by these Examples.

Example 1. Preparation of Sorijai extract

Sorijae ( Rumex crispus L. ) of the present invention was purchased from the National Nakdong River Biological Resources Bank Biological Resources Bank (20160014N049). Sorijae root was extracted with 70% ethanol to prepare an extract of the present invention.

Example 2. Effect of Soridae extract on hyperinsulin-derived diabetic symptoms

In diabetic zebrafish induced by excessive insulin, the antidiabetic effect of the extract was tested.

Specifically, zebrafish larvae after 3 days of fertilization (3 days post fertilization) were placed in a 6-well and then exposed to 10 μM insulin for 48 hours. After exposure to a 0.03% sea salt solution for 24 hours, 1 μg/mL of Sorijay extract was treated for 24 hours. For direct observation of pancreatic islets, a fluorescence microscope (Olympus 1×70, Olympus, Japan) was used and stained with 40 μM 2-NBDG for 30 minutes before fluorescence microscopy. The size of the pancreatic islet of zebrafish was analyzed using Focus Lite software for images acquired through a fluorescence microscope.

As a result of the analysis, it was found that the size of the pancreatic islet in the group treated with the sorijae extract was significantly increased compared to the untreated control group (FIG. 1). Thus, the anti-diabetic effect of the extract of Sorijai was confirmed.

[Formulation example]

The following formulations were prepared using the extract of Sorijai. However, the following formulation examples are merely illustrative of the present invention, and the content of the present invention is not limited thereby.

Formulation Example 1. Preparation of tablets

Singer's Extract 200 mg

lactose 100 mg

starch 100 mg

magnesium stearate appropriate amount

Tablets were prepared by mixing and tableting the above ingredients according to a conventional tablet manufacturing method.

Formulation Example 2. Preparation of liquid formulation

Singer's Extract 1000 mg

CMC-Na 20 g

Lee Seonghwadang 20 g

lemon flavor appropriate amount

Purified water was added to adjust the total volume to 1000 ml. After mixing the above ingredients according to a conventional liquid preparation method, it was filled in a brown bottle and sterilized to prepare a liquid preparation.

Formulation Example 3. Preparation of capsules

Singer's Extract 300 mg

crystalline cellulose 3 mg

lactose 14.8 mg

magnesium stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients were mixed and filled in a gelatin capsule to prepare a capsule.

Formulation Example 4. Preparation of injection

Singer's Extract 300 mg

mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ 12H ₂ O 26 mg

According to a conventional injection preparation method, the content of the above ingredients per 1 ampoule (2 ml) was prepared.

From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without changing the technical spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention, rather than the above detailed description, all changes or modifications derived from the meaning and scope of the following claims and their equivalents.

Claims (6)

A pharmaceutical composition for the prevention or treatment of diabetes comprising the extract or a fraction thereof as an active ingredient.
The pharmaceutical composition of claim 1, wherein the extract is prepared by extraction with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
The pharmaceutical composition of claim 1, wherein the diabetes is type 1 diabetes or type 2 diabetes.
A method for treating diabetes, comprising administering the composition of any one of claims 1 to 3 to a subject other than a human.
A food composition for preventing or improving diabetes, comprising the extract or a fraction thereof as an active ingredient.
A health functional food composition for the prevention or improvement of diabetes, comprising the extract or a fraction thereof as an active ingredient.

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