KR102266256B1 - Pharmaceutical composition comprising Astragali radix derivatives and Lithospermi radix derivatives for anti-diabetes - Google Patents

Abstract

The present invention relates to an antidiabetic pharmaceutical composition, and more particularly, to an antidiabetic pharmaceutical composition capable of effectively reducing blood sugar levels and having fewer side effects.

Description

Pharmaceutical composition for anti-diabetes comprising Astragalus extract and Shichitake extract as active ingredients {Pharmaceutical composition comprising Astragali radix derivatives and Lithospermi radix derivatives for anti-diabetes}

The present invention relates to an antidiabetic pharmaceutical composition, and more particularly, to an antidiabetic pharmaceutical composition capable of effectively reducing blood sugar levels and having fewer side effects.

Recently, the prevalence of chronic diseases such as diabetes and high blood pressure and immune diseases such as inflammatory diseases is increasing due to aging, increase in social stress, and rapid change in dietary culture.

In particular, diabetes mellitus is a disease classified as a metabolic syndrome along with obesity and hyperlipidemia. It is caused by insufficient or abnormal action of insulin secreted by the pancreas. It is a disease in which cholesterol or triglycerides are converted. When you have diabetes, your body cannot make enough insulin, or the insulin produced does not work properly on cells, so blood sugar levels rise, and excess sugar is excreted in the urine, so you lose energy and feel fatigued easily. will cause

In Korea, it is known that about 5% of adults are diabetic, and if not properly treated, complications such as diabetic retinopathy, diabetic nephropathy, vascular disorders, neuropathy, and arteriosclerosis complications occur, resulting in total death. It is a serious disease that occupies the third leading cause.

The inflammatory response is involved in the basis of metabolic syndrome including diabetes. That is, if the inflammatory stimulus generated in the body becomes chronic, it causes metabolic diseases. Therefore, it is effective to prevent and enhance improvement of metabolic diseases such as diabetes by suppressing the inflammatory reaction as well as the symptoms of diabetes itself.

Drugs for the treatment of diabetes have already been developed, and insulin-dependent diabetes, which is a kind of autoimmune disease [type 1 diabetes mellitus; For insulin-dependent diabetes mellitus (IDDM)], insulin preparations are effective and non-insulin-dependent diabetes mellitus [type 2 diabetes mellitus; Non-insulin-dependent diabetes mellitus (NIDDM)] uses sulphonylurease (tolbutamide, chloropropamide, glibenclamide, etc.) and biguanides (metofrmin) drugs. It is essential to use these drugs together, and in order to prevent the exacerbation of diabetes, careful attention is always required in daily life such as diet control and weight management.

Therefore, there is a need to develop functional foods that are effective for treatment as well as preventive effects by consuming them naturally in the same way as with daily meals.

However, conventional drugs or foods used for diabetes have poor sustained drug efficacy, and side effects such as inducing renal toxicity and hepatotoxicity in the body have been reported. Therefore, it was required to develop a product that can reduce these side effects and at the same time discover a natural product in the form of a food having an excellent pharmacological effect and use it to prevent diabetes.

Astragalus is a perennial herb belonging to the legume family, which grows wild in the central and northern regions of Korea and is widely cultivated for medicinal purposes. , diuretic, etc., antibacterial activity, antioxidant activity, and physiological activity according to the content of a large amount of polyphenols and isoflavonoids have been reported.

Zuccarini (Lithospermum erythorihizon Shiebold et. Zuccarini) is a perennial plant belonging to the genus Lithospermum of the Borraginaceae family. it is a plant Chichi is already used in prescription drugs for anti-inflammatory, detoxifying, and antipyretic purposes. It has sterilization and anti-inflammatory properties, so it is used externally as an ointment for swelling, burns, frostbite, eczema and hemorrhoids. .

However, to date, there has been no report on the antidiabetic effect of the complex of Astragalus extract and Chichii extract, and the present inventors overcome the limitations of existing drugs developed for the treatment of diabetes, and can effectively reduce blood sugar levels and have side effects. As a result of conducting research to develop a small number of new drugs, the present invention was completed by confirming that the complex of Astragalus extract and Jichi extract has an excellent antidiabetic effect.

Republic of Korea Patent Publication No. 10-2006-0121576

An object of the present invention is to provide a pharmaceutical composition for anti-diabetes that can effectively reduce blood sugar levels and have fewer side effects.

Another object of the present invention is to provide a health functional food for antidiabetic excellent in the inhibitory effect on the increase in blood sugar level.

In order to solve the problems of the present invention described above, the present invention provides a pharmaceutical composition for antidiabetic comprising an extract of Astragali radix and an extract of Lithospermi radix as active ingredients.

According to an embodiment of the present invention, the astragalus extract and the extract of Chichisis _{may be extracted with at least one solvent selected from water, C 1} to C ₄ alcohol, ethyl acetate, chloroform and hexane, respectively.

In addition, according to an embodiment of the present invention, the temperature of the solvent may be 30 ~ 90 ℃.

In addition, according to an embodiment of the present invention, the astragalus extract and the extract of chives may be included in a weight ratio of 5:5 to 9:l.

In addition, the present invention provides a health functional food for anti-diabetes comprising astragalus (Astragali radix) extract and an extract of Lithospermi radix as active ingredients.

The anti-diabetic pharmaceutical composition of the present invention has excellent inhibitory effect on the increase in blood sugar level due to diabetes, so it can be widely used in the anti-diabetic pharmaceutical composition and anti-diabetic health functional food.

1A is a graph showing the change in body weight according to time of each experimental group.
Figure 1b is a graph showing the dietary intake of each experimental group.
2 is a graph illustrating blood glucose levels according to time of each experimental group.
3 is a graph showing the results of pancreatic weight measurement of each experimental group.
4A is a graph showing the liver weight of each experimental group.
4B is a graph showing the spleen weight of each experimental group.
Figure 4c is a graph showing the lung weight of each experimental group.
4D is a graph showing the kidney weights of each experimental group.

The present invention sought to solve the above-mentioned problems by providing a pharmaceutical composition for antidiabetes comprising astragalus (Astragali radix) extract and a chichi (Lithospermi radix) extract as active ingredients. Through this, it has few side effects when applied in vivo and can be used as a pharmaceutical composition or health functional food with excellent antidiabetic effect by effectively suppressing an increase in blood sugar level.

The term “pharmaceutical composition” refers to a mixture in which other chemical components such as a diluent or carrier are mixed with the mixture of the Astragalus extract and the Astragalus extract of the present invention.

The term “carrier” is defined as a compound that facilitates the addition of the compound into a cell or tissue. For example, dimethylsulfoxide (DMSO) is a commonly used carrier that facilitates the introduction of many organic compounds into cells or tissues of living organisms.

The term “diluent” is defined as a compound that not only stabilizes the biologically active form of the subject compound, but is diluted in water which will dissolve the compound. Salts dissolved in buffer solutions are used as diluents in the art. A commonly used buffer solution is phosphate buffered saline because it mimics the salt state of human solutions. Because buffer salts can control the pH of a solution at low concentrations, buffer diluents rarely modify the biological activity of a compound.

Unless otherwise defined, all technical terms used in the present invention have the meanings commonly understood by one of ordinary skill in the art of the present invention. In addition, although preferred methods and samples are described herein, similar or equivalent ones are also included in the scope of the present invention.

Hereinafter, with reference to the accompanying drawings, the embodiments of the present invention will be described in detail so that those of ordinary skill in the art to which the present invention pertains can easily implement them. The present invention may be embodied in many different forms and is not limited to the embodiments described herein.

The present invention provides a pharmaceutical composition for antidiabetic comprising astragalus (Astragali radix) extract and an extract of Lithospermi radix as active ingredients.

The astragalus extract may be extracted by applying a method used for extraction of astragalus known in the art, and may be, for example, a solvent extraction method, but is not limited thereto. In addition, the Astragalus extract may be prepared as a fraction purified by further performing an additional fractionation process using column chromatography.

The astragalus as an extraction target can be purchased and used commercially available, and it is preferable to use it after removing foreign substances such as soil before performing the extraction process.

The extract of borage extract may be extracted by applying a method used for extracting borage known in the art, and may be, for example, a solvent extraction method, but is not limited thereto. In addition, the Jichi extract may be prepared as a purified fraction by further performing an additional fractionation process using column chromatography.

The extract target can be purchased and used commercially available, it is preferable to use it after removing foreign substances such as soil before performing the extraction process.

When extracting the above-mentioned Astragalus and Chili using the solvent extraction method, the solvent used may be extracted with a solvent of a single or mixed form such as water, C1-C4 lower alcohol, ethyl acetate, chloroform or hexane, more preferably Preferably, it may be a C ₁ to C ₄ alcohol, and even more preferably ethanol.

In addition, the temperature of the solvent may be 30 ~ 90 ℃ , and the astragalus extract and chia extract extracted in the above temperature range may further increase the content of the active ingredient exhibiting an antidiabetic effect.

As the astragalus extract and chia extract extracted according to the above-described embodiment are mixed and used, it is superior in antidiabetic effect compared to the case where the astragalus extract or jichi extract is used alone, and the expression of a more synergistic effect on the effect In a preferred embodiment of the present invention for this, the Astragalus extract and the extract of Jichi may be included in a weight ratio of 5:5 to 9:1.

The pharmaceutical composition according to the present invention is formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively. can be used

The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person of ordinary skill in the art to which the present invention pertains. or may be prepared by inclusion in a multi-dose container.

Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are commonly used in formulation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil; However, the present invention is not limited thereto.

The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like, in addition to the above components. Suitable pharmaceutically acceptable carriers and agents are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, intrapulmonary administration and rectal administration etc. can be administered. When administered orally, the protein or peptide is digestible and therefore oral compositions should be formulated to coat the active agent or to protect it from degradation in the stomach. The pharmaceutical composition may also be administered by any device capable of transporting the active substance to a target cell.

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration mode, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate and reaction sensitivity of the patient, An ordinarily skilled physician can readily determine and prescribe a dosage effective for the desired treatment or prophylaxis.

The pharmaceutical composition of the present invention may be administered as an individual prophylactic or therapeutic agent, or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents.

In addition, the present invention also provides a health functional food for anti-diabetes containing astragalus (Astragali radix) extract and chichi (Lithospermi radix) extract as active ingredients.

The type of the health functional food composition is not particularly limited as long as it is commonly manufactured and/or sold. For example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, etc. It can be used in the form of pills, powders, granules, needles, tablets, capsules or beverages, and includes all health functional foods in a conventional sense.

The health beverage composition of the present invention is not particularly limited in the liquid component except for containing the Astragalus extract and the Astragalus extract, and may contain various flavoring agents or natural carbohydrates as additional components as in a conventional beverage.

In general, the amount of the astragalus extract and the extract of Chichisis contained in the health functional food may be included in an amount of 0.1 to 50% by weight, preferably 1 to 40% by weight of the total food weight. In addition, in the case of long-term intake for the purpose of health and hygiene or health control, it 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 above the above range.

Hereinafter, an example of the preparation of the health functional food for anti-diabetes of the present invention will be described, but the present invention is not intended to be limited thereto, but only to be described in detail.

<Production Example 1>

Astragalus extract 140 mg

Borage extract 60 mg

70 μg vitamin A acetate

Vitamin E 1.0 mg

Vitamin B 1 0.13 mg

Vitamin B 2 0.15 mg

Vitamin B 6 0.5mg

0.2 μg of vitamin B 12

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

50 μg folic acid

Calcium pantothenate 0.5 mg

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Hereinafter, the present invention will be described in more detail through the accompanying examples. However, these drawings and the following examples are only examples for easily explaining the content and scope of the technical idea of the present invention, and thereby the technical scope of the present invention is not limited or changed. In addition, it can be easily determined by those skilled in the art that various modifications and changes are possible within the scope of the technical spirit of the present invention based on these examples.

(Example 1)

1-1. Preparation of Astragalus Extract

One-year-old Chichi root (Jecheonsan) samples were purchased from the Korea Herbal Medicine Association and coarsely pulverized with chumal, and 50% ethanol 15 times the weight of the building material sample and the weight of the building material sample was added, followed by reflux extraction at 80° C. for 4 hours. Reflux extraction was repeated twice under the same conditions, followed by filtration and concentration to prepare Astragalus extract.

1-2. Preparation of borage extract

One-year-old Chichi root (Jecheonsan) samples were purchased from the Korea Herbal Medicine Association and coarsely crushed with chumal, and 70% ethanol 15 times the weight of the building material sample and the weight of the building material sample was added, followed by reflux extraction at 80° C. for 4 hours. The reflux extraction was repeated twice under the same conditions, followed by filtration and concentration to prepare a Chichi extract.

1-3. Mixture of Astragalus extract and Borage extract

The astragalus extract and the Chichi extract were mixed in a weight ratio of 7:3 and concentrated to prepare an astragalus complex.

(Comparative Example 1)

The guava leaf extract used as a control in the present invention was purchased from Natural FNP Co., Ltd. as a functional raw material approved individually by the Ministry of Food and Drug Safety and used.

(Experimental Example 1) Weight change measurement

The experimental group was classified into a normal group, an alloxan-treated group, an astragalus complex administered to the alloxane-treated group, and a guava leaf extract administered to the alloxane-treated group with a guava leaf extract.

To observe the antidiabetic effect, Astragalus complex and guava leaf extract were orally administered once a day at concentrations of 1 mg/mouse and 3 mg/mouse, respectively, 10 times in total to the alloxane-treated group.

Referring to FIG. 1A , it can be seen that the weight of the alloxane-treated group was significantly reduced on the 9th day after diabetes induction compared to the normal group.

The group administered with Astragalus complex at a concentration of 1 mg/mouse was superior to the group administered with Astragalus complex at a concentration of 3 mg/mouse.

In the case of diabetes, various complications or accompanying symptoms follow, one of which is an increase in the amount of food eaten. This phenomenon is caused by polyuria and abnormal glucose absorption and is also observed in diabetic-induced animals.

The amount of food intake was measured by fasting the mice for 12 hours, fasting them, and then giving them feed for 4 hours.

Referring to FIG. 1b , it can be seen that the dietary intake of the alloxane-treated group was significantly increased compared to the normal group, and the decrease in the dietary intake according to the concentration of the Astragalus complex administered group did not show a significant difference.

(Experimental Example 2) Measurement of blood sugar level

Since the blood sugar level increases according to the induction of diabetes, the blood sugar level according to time of each experimental group was measured after the induction of diabetes, and the results are shown in FIG. 2 .

Referring to FIG. 2 , it can be seen that the normal group did not show a change in blood glucose level after diabetes induction, and the alloxane-treated group significantly increased the blood glucose level over time after diabetes induction. It was confirmed that the group administered with Astragalus complex on the 9th day after inducing diabetes was able to reduce blood sugar levels to a level similar to that of the normal group, and it was confirmed that the effect of reducing blood sugar levels was superior to that of the group administered with guava leaf extract, a raw material of the notification type.

(Experimental Example 3) Measurement of changes in pancreas weight

Since the weight decreases due to damage to the pancreas according to the induction of diabetes, the weight of the pancreas in each experimental group was measured on the 9th day after diabetes induction, and the results are shown in FIG. 3 .

Referring to FIG. 3 , it can be seen that the pancreas weight of the alloxane-treated group was significantly reduced compared to the normal group.

The group administered with Astragalus complex at a concentration of 1 mg/mouse was superior to the group administered with Astragalus complex at a concentration of 3 mg/mouse in the inhibition of pancreatic weight loss, and it was confirmed that it was superior to the group administered with guava leaf extract, the raw material of the notification type.

(Experimental Example 4) Toxicity evaluation

Four tissues (liver, spleen, lung and kidney) were weighed to determine whether the administration of the Astragalus complex and long-term toxicity due to a high-fat diet was performed, and the weight measurement results are shown in FIGS. 4A to 4D . As a result of measuring the tissue weight of the groups administered with the Astragalus complex, the Astragalus extract had no significant effect on the weight loss, but the organ weight loss was smaller in the group administered with Astragalus complex at 1 mg/mouse concentration than the group administered with Astragalus complex at 3 mg/mouse concentration. that can be checked

Claims (5)

As an antidiabetic pharmaceutical composition for type 1 diabetes comprising a mixed extract mixed with an ethanol extract of Astragali radix and an ethanol extract of Lithospermi radix as an active ingredient,
The Astragalus ethanol extract is extracted with 70% ethanol aqueous solution,
The Jichi ethanol extract is extracted with 50% ethanol aqueous solution,
The Astragalus ethanol extract and Chichii ethanol extract are mixed in a weight ratio of 7: 3,
The mixed extract is an antidiabetic pharmaceutical composition for type 1 diabetes, characterized in that it inhibits damage to an organ selected from the group consisting of pancreas, liver, spleen, lung and kidney caused by diabetes. delete delete delete As a health functional food for antidiabetes for type 1 diabetes, comprising a mixed extract mixed with Astragali radix ethanol extract and Lithospermi radix ethanol extract as an active ingredient,
The Astragalus ethanol extract is extracted with 70% ethanol aqueous solution,
The Jichi ethanol extract is extracted with 50% ethanol aqueous solution,
The Astragalus ethanol extract and Chichii ethanol extract are mixed in a weight ratio of 7: 3,
The mixed extract is an anti-diabetic health functional food for type 1 diabetes, characterized in that it inhibits the damage to an organ selected from the group consisting of pancreas, liver, spleen, lung and kidney caused by diabetes.

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