KR102183915B1 - Composition containing complex extracts for improving blood circulation - Google Patents

Abstract

The present invention provides a composition comprising as an active ingredient a complex extract consisting of an Angelica root extract, Baekshou extract and ginkgo leaf extract. The composition of the present invention has excellent thrombus formation inhibitory effect by the synergistic effect of the complex extract consisting of Angelica keiskei extract, Baekshou extract and ginkgo biloba extract, and at the same time has excellent blood cholesterol lowering effect and blood triglyceride lowering effect. Accordingly, the composition of the present invention may be implemented as a pharmaceutical product or a health functional food for preventing, improving or treating blood circulation, thrombosis, and dyslipidemia.

Description

Composition containing complex extracts for improving blood circulation

The present invention relates to a composition for improving blood circulation comprising a complex extract, and more particularly, to a variety of pharmaceutical uses or health functional food urethra of the herbal compound extract based on the effect of inhibiting blood clot formation, the effect of lowering blood cholesterol, etc. will be.

In recent years, not only developed countries, but also circulatory diseases such as arteriosclerosis, cerebral hemorrhage, high blood pressure, heart disease, stroke, and cerebral infarction occupy the 1st and 2nd causes of death in Korea, along with an increase in the obese population due to excessive nutrition due to the westernization of diet. These geriatric diseases are frequently occurring in middle and elderly people due to changes in dietary habits and internal and external environmental stresses as they develop into modern society. In addition, the above diseases may occur due to blockage of blood vessels due to various causes. For example, when cardiovascular is blocked, myocardial infarction may occur, and when blood vessels in the brain are blocked, cerebral infarction may occur. In addition, if the cerebral infarction continues, symptoms of a stroke can occur, which can lead to death. In the United States, stroke is the third-highest cause of death among adults, and it is known that mobility is the largest factor in disability. The main cause of these diseases is known as thrombus, and thrombus is recognized as a pathological phenomenon mediated by excessive platelet aggregation. In addition, when a blood clot occurs, blood vessels in the area are narrowed or blocked, resulting in blood circulation disorders. In addition, when the concentration of blood cholesterol or blood triglycerides increases, blood circulation may be impaired.

Therefore, many studies have been conducted on pharmaceutical materials or health functional food materials that can effectively control blood cholesterol and triglyceride concentrations while suppressing the formation of blood clots for improvement of blood circulation and prevention or treatment of thrombotic diseases. On the other hand, natural edible materials have great significance in terms of economic and industrial terms, and since most of them have no side effects on the human body, there is an urgent need to develop natural edible materials that are effective in improving blood circulation.

Regarding the natural food and drug material having the effect of improving blood circulation, Korean Patent Publication No. 10-1404168 discloses a pharmaceutical composition for preventing or treating thrombosis containing the butanol fraction of ethanol extract of Angelica gigas as an active ingredient. Has been. In addition, Korean Laid-Open Patent Publication No. 10-2011-0125960 discloses a pharmaceutical composition for reducing blood clots containing an ethanol extract of Cynanchum wilfordii as an active ingredient. In addition, products containing ginkgo biloba extract that help improve blood circulation are commercially available. In addition, Korean Patent Application Publication No. 10-2018-0042035 discloses a pharmaceutical composition for preventing or treating dyslipidemia containing an extract of Angelica gigas as an active ingredient. In addition, Korean Patent Laid-Open Publication No. 10-2011-0125958 discloses Baek Ha Soo ( Cynanchum wilfordii ) A pharmaceutical composition for lowering blood cholesterol containing an ethanol extract as an active ingredient is disclosed . In addition, US Patent Publication No. 2008/0254155 discloses a composition for lowering blood cholesterol comprising a ginkgo leaf extract as an active ingredient.

The present invention is derived from the conventional technical background, and an object of the present invention is to improve blood circulation, prevent, improve or treat thrombotic diseases, etc. It is in providing food use.

The inventors of the present invention conducted a study to develop an extract having an effect of inhibiting blood clot formation targeting a number of natural products that are safe compared to synthetic chemicals. As a result, it was confirmed that the complex extract consisting of the extract of Angelica Angelica, the extract of Baekshui and the extract of ginkgo biloba has an excellent effect of inhibiting blood clot formation by synergistic action, and at the same time has excellent effect of lowering blood cholesterol and lowering blood triglycerides. Was completed.

In order to achieve the above object, an example of the present invention provides a composition for improving blood circulation, comprising a complex extract consisting of an extract of champignon angelica, baekshui extract and ginkgo leaf extract as an active ingredient.

In order to achieve the above object, an example of the present invention provides a composition for preventing, improving, or treating thrombotic diseases comprising a complex extract consisting of an extract of Cham Angelica, Baekshui extract, and Ginkgo biloba extract as an active ingredient.

In order to achieve the above object, an example of the present invention provides a composition for preventing, improving, or treating dyslipidemia comprising a complex extract consisting of an extract of Angelica Angelica, Baekshou extract and Ginkgo leaf extract as an active ingredient.

The composition is preferably in the form of a pharmaceutical composition or a food composition.

The composition of the present invention has excellent thrombus formation inhibitory effect by the synergistic effect of the complex extract consisting of Angelica keiskei extract, Baekshou extract and ginkgo biloba extract, and at the same time has excellent blood cholesterol lowering effect and blood triglyceride lowering effect. Accordingly, the composition of the present invention may be implemented as a pharmaceutical product or a health functional food for preventing, improving or treating blood circulation, thrombosis, and dyslipidemia.

1 is a result of analyzing the antioxidant efficacy of the complex extract prepared in Preparation Example 4 of the present invention using the DPPH test method.
Figure 2 shows the results of the antithrombotic efficacy evaluation experiment of the complex extract using a thrombosis-inducing animal model as a value of protection (%).
Figure 4 shows the content of triglycerides in plasma among the experimental results using the obesity-inducing animal model, Figure 5 shows the total cholesterol content in the plasma of the experimental results using the obesity-inducing animal model, and Figure 6 is It shows the LDL cholesterol content in plasma among the experimental results using the model.

Hereinafter, terms used in the present invention will be described.

As used herein, the terms "pharmaceutically acceptable" and "foodically acceptable" mean not significantly irritating the organism and not inhibiting the biological activity and properties of the administered active substance.

The term "prevention" as used in the present invention refers to any action that suppresses symptoms or delays progression of a specific disease (eg, thrombotic disease) by administration of the composition of the present invention.

The term "improvement" as used herein refers to any action that at least reduces the severity of a parameter related to the condition being treated, for example a symptom.

The term "treatment" used in the present invention refers to any action that improves or beneficially alters the symptoms of a specific disease (eg, thrombotic disease) by administration of the composition of the present invention.

As used herein, the term "administering" means providing a given composition of the present invention to a subject by any suitable method. At this time, the individual refers to all animals, such as humans, monkeys, dogs, goats, pigs, mice, etc., having diseases in which symptoms of a specific disease can be improved by administering the composition of the present invention.

The term "pharmaceutically effective amount" as used herein refers to an amount sufficient to treat a disease at a reasonable benefit or risk ratio applicable to medical treatment, which is the type, severity, activity of the drug, drug Sensitivity to, administration time, route of administration and rate of excretion, duration of treatment, factors including drugs used simultaneously, and other factors well known in the medical field.

Hereinafter, the present invention will be described in detail. The present invention includes a composition comprising a complex extract consisting of extracts of three herbal medicines as an active ingredient. The complex extract is specifically composed of an angelica root extract, baekshui extract, and ginkgo leaf extract. The composition of the present invention improves blood circulation; Preventing, ameliorating or treating thrombotic diseases; It can be used for various pharmaceutical uses or health functional foods such as prevention, improvement or treatment of dyslipidemia.

The Angelica gigas is a perennial plant belonging to the umbel family of Ipanhwa group, a dicotyledonous plant, and uses its root as a medicinal material. The Baeksu-o ( Cynanchum wilfordii ) is a tendril perennial plant belonging to the Asclepiadaceae genus Cynanchum, and uses its root as a medicinal material. In the present invention, the part of the plant for obtaining the Angelica keiskei extract or Baekshou extract is not greatly limited, such as roots, stems, leaves, flowers, seeds, etc., and is preferably a root when considering efficacy.

The complex extract, which is the active ingredient of the composition according to the present invention, can be prepared by various methods. For example, the complex extract may be prepared by mixing Angelica Angelica, Baekshou, and Ginkgo biloba, and then adding an extraction solvent thereto and extracting the mixed extract, or by adding alcohol having 3 to 8 carbon atoms to the mixed extract and fractionating It can also be manufactured. In addition, the complex extract may be prepared by mixing the extracts from Angelica, Baeksuo and Ginkgo biloba, respectively. Specifically, Angelicae extract, Baekshou extract or Ginkgo biloba extract constituting the complex extract may be prepared using a conventional extraction method known in the art, for example, a solvent extraction method. The extraction solvent used in the solvent extraction method is water, a lower alcohol having 1 to 4 carbon atoms (e.g., methanol, ethanol, propanol, and butanol) or a mixture thereof, which is a water-containing lower alcohol, propylene glycol, 1,3-butylene glycol. , Glycerin, acetone, diethyl ether, ethyl acetate, butyl acetate, dichloromethane, chloroform, hexane, and may be selected from the group consisting of a mixture thereof, of which water, alcohol or a mixture thereof is preferably selected from a hydrous alcohol. And it is more preferable that it is a hydrous alcohol. When using water as the extraction solvent, it is preferable that water is hot water. In addition, when using alcohol as the extraction solvent, the alcohol is preferably a lower alcohol having 1 to 4 carbon atoms, and the lower alcohol is more preferably selected from methanol or ethanol. In addition, when using a hydrous alcohol as the extraction solvent, the alcohol content is preferably 50 to 90%, more preferably 60 to 85%. On the other hand, it is obvious to those skilled in the art that not only the above-described extraction solvent but also other extraction solvents can be used to obtain substantially the same effect. In addition, the Angelicae extract, Baekshou extract, or Ginkgo biloba extract constituting the complex extract includes not only the extract by the above-described extraction solvent, but also extracts obtained through other conventional extraction methods, fractions, purified products, and extracts subjected to fermentation. I can. For example, extraction by supercritical fluid extraction using carbon dioxide, extraction by extraction using ultrasonic waves, separation using an ultrafiltration membrane having a certain molecular weight cut-off value, or various chromatography (size, charge, Active fractions obtained through various purification and extraction methods additionally performed, such as separation by separation by hydrophobicity or those produced for separation according to affinity), extraction by fermentation products of various microorganisms, etc. are also included in the extract of the present invention. In general, a supercritical fluid has the properties of a liquid and a gas when the gas reaches a critical point under high temperature and high pressure conditions, and has a polarity similar to that of a non-polar solvent chemically. Due to this characteristic, the supercritical fluid is not suitable for extraction of oil-soluble substances. It is used (J. Chromatogr. A. 1998;479:200-205). Carbon dioxide becomes a supercritical fluid having both liquid and gaseous properties as the pressure and temperature reach a critical point due to the operation of the supercritical fluid device, and as a result, the solubility of the oil-soluble solute increases. When the supercritical carbon dioxide passes through an extraction container containing a certain amount of a sample, the fat-soluble substance contained in the sample is extracted and released into the supercritical carbon dioxide. After extracting the fat-soluble substance, if the sample remaining in the extraction container is passed through the supercritical carbon dioxide containing a small amount of co-solvent again, components that were not extracted with pure supercritical carbon dioxide can be extracted. The supercritical fluid used in the supercritical extraction method of the present invention can effectively extract an active ingredient by using a supercritical carbon dioxide or a mixed fluid in which a co-solvent is additionally mixed with carbon dioxide. As such a co-solvent, one or a mixture of two or more selected from the group consisting of chloroform, ethanol, methanol, water, ethyl acetate, hexane, and diethyl ether may be used. Most of the extracted samples contain carbon dioxide, but carbon dioxide is volatilized into the air at room temperature, and the co-solvent can be removed with a vacuum evaporator. In addition, the ultrasonic extraction method is an extraction method that uses energy generated by ultrasonic vibration, and the ultrasonic waves can destroy the insoluble solvent contained in the sample in the aqueous solvent, and due to the high local temperature generated at this time, Since the kinetic energy of the reactant particles is increased, sufficient energy required for the reaction is obtained, and high pressure is induced by the impact effect of ultrasonic energy to increase the mixing effect of the material contained in the sample and the solvent, thereby increasing the extraction efficiency. The extraction solvent that can be used in the ultrasonic extraction method may be one or a mixture of two or more selected from the group consisting of chloroform, ethanol, methanol, water, ethyl acetate, hexane, and diethyl ether. The extracted sample may be vacuum filtered to recover the filtrate, then removed with a vacuum evaporator, and freeze-dried to obtain an extract through a conventional extract preparation method. In addition, the extract of Korean Angelica, Baekshou extract, or Ginkgo biloba extract constituting the complex extract also includes an extract that has undergone a fermentation process. For example, the fermented extract of Korean Angelica can be prepared as follows. After finely crushing the angelica root to about 100 to 500 mesh, a conventional culture solution for microorganisms was added to a concentration of 1 to 50 g/L, and microorganisms such as yeast strains or lactic acid bacteria were added in an amount of 10,000 to 100,000 cfu/L. Add as. Thereafter, the culture is carried out for about 5 to 10 days in an aerobic or anaerobic condition under normal microbial culture conditions such as a culture temperature of 30 to 37°C and a pH of 5 to 7. Thereafter, through aging and filtration, a fermented extract of Cham Angelica can be obtained. The fermented extract of Baekshou or the fermented extract of ginkgo leaves may also be prepared through the same process.

In the composition according to the present invention, the mixing ratio of the extract of Cham Angelica, Baekshou extract and Ginkgo biloba extract constituting the complex extract, which is an active ingredient, is not limited. For example, in the complex extract, the weight ratio of Angelicae extract, Baekshou extract, and Ginkgo biloba extract may be selected from 1: (0.5-2): (0.5-2), and when considering synergistic action, 1: (0.6 ~1.5): It is preferably selected from (0.6 to 1.5), and more preferably selected from 1: (0.8 to 1.2): (0.8 to 1.2).

The complex extract used as an active ingredient in the composition of the present invention has an excellent effect of inhibiting blood clot formation by synergistic effect of the combination of Angelica Angelica extract, Baekshou extract, and Ginkgo biloba extract, and at the same time has excellent blood cholesterol lowering effect and blood triglyceride lowering effect. Have. Accordingly, the composition of the present invention may be implemented as a pharmaceutical product or a health functional food for preventing, improving or treating blood circulation improvement, thrombotic disease, or dyslipidemia. In addition, the complex extract used as an active ingredient in the composition of the present invention has excellent radical scavenging activity and can be used as a component of an antioxidant composition. In addition, the complex extract used as an active ingredient in the composition of the present invention may be used as a component of the composition for preventing, improving or treating obesity. In addition, the complex extract used as an active ingredient in the composition of the present invention may be used as a component of the composition for preventing, improving or treating metabolic syndrome. The metabolic syndrome is a disease in which one or more diseases selected from hyperlipidemia, cardiovascular disease, hypertension or arteriosclerosis occur simultaneously with obesity.

In the present invention, the thrombotic disease is a disease caused by a blood clot, and its type is not limited, for example, arterial thrombosis, venous thrombosis, pulmonary artery embolism, chronic venous ischemia, varicose veins, deep vein thrombosis, arteriosclerosis, cerebral hemorrhage, stroke. And it may be any one or more selected from the group consisting of cerebral infarction.

In the present invention, dyslipidemia refers to a state in which total cholesterol, LDL cholesterol, triglycerides are increased or HDL cholesterol is decreased in the blood, and is one or more selected from the group consisting of hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. I can. The hyperlipidemia refers to a state in which lipids including cholesterol and triglycerides are increased in blood. Hyperlipidemia can increase the risk of coronary artery disease, such as atherosclerosis or myocardial infarction, even if it does not show symptoms. The hypercholesterolemia is a state in which cholesterol is increased in the blood, and total cholesterol and LDL cholesterol are high. The hypertriglyceridemia refers to a state in which triglycerides are increased in blood.

The composition comprising the complex extract of the present invention as an active ingredient may be embodied as a pharmaceutical composition, food additive, food composition (especially health functional food), or feed additive depending on the purpose or aspect of use, and the complex extract in the composition The content of the composition may also be adjusted in various ranges according to the specific form of the composition, the purpose of use or the aspect of use.

The content of the complex extract as an active ingredient in the pharmaceutical composition of the present invention is not limited, for example, 0.1 to 99% by weight, preferably 0.5 to 50% by weight, more preferably 1 to 30% based on the total weight of the composition. It may be weight percent. In addition, the pharmaceutical composition of the present invention may further include additives such as a pharmaceutically acceptable carrier, excipient, or diluent in addition to the complex extract. Carriers, excipients and diluents that can be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate. , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils. In addition, the pharmaceutical composition of the present invention improves blood circulation in addition to the complex extract; Preventing, ameliorating or treating thrombotic diseases; It may further contain one or more known active ingredients having the effect of preventing, improving or treating dyslipidemia. The pharmaceutical composition of the present invention can be formulated into a dosage form for oral administration or a dosage form for parenteral administration by a conventional method. When formulated, such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. It can be formulated using diluents or excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient such as starch, calcium carbonate, and water in the complex extract as an active ingredient. It can be prepared by mixing sucrose, lactose or gelatin. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups.In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. have. Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used. Furthermore, it can be preferably formulated according to each disease or component by an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (latest edition), Mack Publishing Company, Easton PA. The pharmaceutical composition of the present invention may be orally or parenterally administered to mammals including humans according to a desired method, and parenteral administration methods include skin external use, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, muscle These include intra- or intrathoracic injection. The dosage of the pharmaceutical composition of the present invention is not largely limited as long as it is a pharmaceutically effective amount, and the range varies according to the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and disease severity. Varies. A typical daily dosage of the pharmaceutical composition of the present invention is not limited, for example, may be selected from 1 to 1000 mg/kg based on the complex extract as an active ingredient, and from 10 to 500 mg/kg It is preferably selected, and more preferably selected from 50 to 250 mg/kg. The number of times of administration of the pharmaceutical composition of the present invention is also not limited, and may be administered once a day or divided into several times a day.

The content of the complex extract, which is an active ingredient in the food composition of the present invention, is not largely limited, and is 0.01 to 50% by weight, preferably 0.1 to 25% by weight, more preferably 0.5 to 10% by weight based on the total weight of the composition. I can. The food composition of the present invention includes the form of pills, powders, granules, needles, tablets, capsules, or liquids, and examples of specific foods include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, Others include noodles, gums, dairy products including ice cream, various soups, beverages, tea, functional water, drinks, alcoholic beverages and vitamin complexes, and all health foods in the usual sense are included. The food composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional component in addition to the complex extract as an active ingredient. In addition, the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acids and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols , Carbonated beverages used in carbonated beverages, and the like. In addition, the food composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These ingredients may be used independently or in combination. The natural carbohydrates described above are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the flavoring agent, natural flavoring agents such as taumatin and stevia extract, or synthetic flavoring agents such as saccharin and aspartame may be used.

Hereinafter, the present invention will be described in more detail through examples. However, the following examples are only intended to clearly illustrate the technical features of the present invention, and do not limit the scope of the present invention.

1. Angelica extract, Baek Shou Preparation of extract, ginkgo biloba extract and complex extract

Preparation Example 1: Preparation of Angelica Angelica extract

The basement of dried Angelica gigas purchased from the Kyungdong Medicinal Market was pulverized and pulverized. Thereafter, about 5 times of 70% (v/v) alcohol was added to the sample of Angelica Angelicae powder, extracted twice at 80° C. for about 4 hr, and filtered. Thereafter, the filtered extract was concentrated under reduced pressure conditions and lyophilized to obtain an Angelica kelp extract. The yield of Angelica Angelica extract was about 32%.

Preparation Example 2: Preparation of Baekshou extract

Dried baekshou ( Cynanchum wilfordii ) purchased from the Kyungdong medicine market was pulverized and powdered. Thereafter, about 5 times of 70% (v/v) alcohol was added to the sample of white water powder, extracted twice for about 4 hr at 80° C., and then filtered. Thereafter, the filtered extract was concentrated under reduced pressure and lyophilized to obtain a Baekshou extract. The yield of the Baekshou extract was about 29.2%.

Preparation Example 3: Preparation of Ginkgo Leaf Extract

Dried ginkgo leaves ( Ginko biloba leaves) purchased from the Kyungdong medicinal market were pulverized and powdered. Thereafter, about 5 times of 70% (v/v) alcohol was added to the ginkgo leaf powder sample, extracted twice for about 4 hr at 80° C., and then filtered. Thereafter, the filtered extract was concentrated under reduced pressure and lyophilized to obtain a ginkgo biloba extract. The yield of the ginkgo leaf extract was about 27.3%.

Preparation Example 4: Preparation of complex extract

A complex extract was prepared by mixing the Korean Angelicae extract prepared in Preparation Example 1, the Baekshou extract prepared in Preparation Example 2, and the ginkgo leaf extract extracted in Preparation Example 3 at a weight ratio of 1:1:1.

2. Analysis of antioxidant efficacy of complex extracts

The antioxidant efficacy of the complex extract prepared in Preparation Example 4 was measured using the DPPH test method. First, a DPPH (1,1-diphenyl-2-2hydrazyl) reagent was prepared by dissolving DPPH (1,1-diphenyl-2-2hydrazyl) in methanol to a concentration of 0.1 mM in the state of breaking the light.

Thereafter, the complex extract prepared in Preparation Example 4 was added to DPPH (1,1-diphenyl-2-2hydrazyl) reagent at concentrations of 50 µg/ml, 100 µg/ml, 500 µg/ml, and 1000 µg/ml, respectively. After reacting for 20 minutes under the condition of blocking light, the absorbance was measured at a wavelength of 517 nm using a microplate reader. Meanwhile, ascorbic acid was added to DPPH (1,1-diphenyl-2-2hydrazyl) reagent at a concentration of 100 μg/ml as a positive control. Then, DPPH radical scavenging activity (%) was calculated using Equation 1 below.

[Equation 1]

1 is a result of analyzing the antioxidant efficacy of the complex extract prepared in Preparation Example 4 of the present invention using the DPPH test method. In FIG. 1,'Control(+)' of the X-axis represents a positive control, and'ACG-1 extract' represents a complex extract prepared in Preparation Example 4. In addition, the antioxidant efficacy analysis results of the composite extract prepared in Preparation Example 4 are shown in Table 1 below.

Processing sample Treatment concentration (㎍/mL) DPPH radical scavenging activity(%) IC ₅₀ of complex extract
(㎍/mL) Complex extract prepared in Preparation Example 4 50 5.6 360.5 100 25.0 500 49.2 1000 86.8

3. Platelet aggregation of complex extracts Inhibitory ability Measure

The ability of the complex extract prepared in Preparation Example 4 to inhibit human platelet aggregation was measured by a turbidity measurement method using an Aggregometer (Chrono-Log Co., Ltd., Havertown, PA, USA). First, the Angelicae extract prepared in Preparation Example 1, Baekshou extract prepared in Preparation Example 2, Ginkgo biloba extract prepared in Preparation Example 3, and the complex extract prepared in Preparation Example 4 were dissolved in 1% DMSO solution at various concentrations. Thus, a sample solution was prepared. Thereafter, human platelets were cultured at 37° C. for 3 minutes, and then the sample solution was treated, and aggregation was induced with collagen, a substance inducing platelet aggregation, and the platelet aggregation rate was measured for 6 minutes. Table 2 below shows the results of measuring platelet aggregation inhibitory ability of the extract prepared in Preparation Example 1, Baekshui extract prepared in Preparation Example 2, Ginkgo biloba extract prepared in Preparation Example 3, and the composite extract prepared in Preparation Example 4. .

Processing sample Treatment concentration (㎍/mL) Platelet aggregation rate (%) Control 0 77.70 Sesame Angelica extract prepared in Preparation Example 1 80 50.33 160 34.33 Baekshui extract prepared in Preparation Example 2 80 64.33 160 59.33 Ginkgo biloba extract prepared in Preparation Example 3 80 63.00 160 59.33 Complex extract prepared in Preparation Example 4 20 54.42 40 53.23 80 45.87 160 37.99 320 11.30

As shown in Table 2, when the complex extract prepared in Preparation Example 4 was treated, the platelet aggregation rate was very low overall compared to the case of treatment with the same concentration criteria of the Angelicae extract, Baekshui extract and Ginkgo biloba extract alone. These results are thought to be due to the synergistic effect on the inhibition of platelet aggregation by the combination of Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract.

4. Conjugate extract using thrombosis-inducing animal model Antithrombotic Efficacy evaluation

5-week-old male ICR-based mice (around 25-30 g) were purchased from RaonBio. It was used in the experiment after acclimatization breeding for 1 week while supplying enough feed and water to the purchased mice. As breeding environmental conditions, use 23±2℃ temperature, 55±15% relative humidity, ventilation 10 to 20 times per hour, lighting time of 12 hr (08:00 ON, 20:00 OFF), and illumination conditions of 150 to 300 Lux. I did. Thrombosis-inducing animal model experiments were conducted according to the experimental method of Diminno et al. Specifically, 50 µl of a mixed solution of collagen and epinephrine (1.4 ug/mouse+ 85 ug/mouse), which is an agent for inducing platelet aggregation, was injected into the tail vein of the mouse. In order to investigate the antithrombotic effect of the drug sample, 90 minutes before injection of the platelet aggregation-inducing agent, the drug sample was administered orally once in proportion to the body weight. There were 10 experimental animals per group, and drug samples were suspended in distilled water and administered. Thereafter, the percentage of the number of experimental animals protected from paralysis or death of the mouse hind limb caused by injection of a platelet aggregation inducer, that is, the protection rate (%), was calculated to evaluate the antithrombotic efficacy of the drug. After the injection of the platelet aggregation-inducing agent, the persistence of paralysis, death, or recovery from paralysis for 15 minutes or more was observed, and the antithrombotic effect of the drug sample was determined. The protection rate (Protection, %) of each experimental group was calculated using Equation 2 below.

[Equation 2]

C: Total number of experimental group

D: The number of dead or paralyzed out of the total population of the experimental group

Figure 2 shows the results of the antithrombotic efficacy evaluation experiment of the complex extract using a thrombosis-inducing animal model as a value of protection (%). In FIG. 2,'Control' on the X-axis is a group in which only distilled water, which is a vehicle, is administered as a drug sample as a control, and'ASA 100' is a positive control, and acetylsalicylic acid (or aspirin) as a drug sample is 100 mg/ It is a group administered at a dose of kg (weight), and'ACG-1 extract' is a group in which the complex extract prepared in Preparation Example 4 as a drug sample was administered at the corresponding dose. In addition, Table 3 below shows the number and protection rate of the dead or paralyzed mice according to the experimental group.

Drugs administered in the experimental group Drug dosage excluding vehicle Number of dead or paralyzed mice Protection rate (%) Distilled water - 8/12 33.3 Acetylsalicylic acid 100 mg/kg(weight) 5/12 58.3 Complex extract prepared in Preparation Example 4 75 mg/kg(weight) 7/12 41.7 150 mg/kg(weight) 6/12 50.0 300 mg/kg(weight) 9/12 25.0

As shown in Table 3, the complex extract prepared in Preparation Example 4 exhibited an effect close to that of acetylsalicylic acid (Acetylsalicylic acid, or aspirin), which is a commercial antithrombotic agent.

5. Evaluation of Cholesterol Lowering and Triglyceride Lowering Efficacy of Complex Extracts Using Obesity Induced Animal Model

(1) Animal testing method

5-week-old male ICR-based mice (around 25-30 g) were purchased from RaonBio. It was used in the experiment after acclimatization breeding for 1 week while supplying enough feed and water to the purchased mice. As breeding environmental conditions, use 23±2℃ temperature, 55±15% relative humidity, ventilation 10 to 20 times per hour, lighting time of 12 hr (08:00 ON, 20:00 OFF), and illumination conditions of 150 to 300 Lux. I did.

General dietary feed for experimental animals (feed containing 6% fat) and high fat feed (feed containing 60% fat) were supplied and used by Raon Bio. The experimental animals were 10 per each group, and the weight of the experimental animals during the breeding period was measured once a week. General dietary feed was fed to the general diet group (n=10) and distilled water was orally administered once a day for 12 weeks. In addition, the high-fat diet group (n=40) was divided into 4 groups of 10 animals each, and a high-fat diet was fed to each experimental group, and a drug sample was suspended in distilled water and administered orally once a day for 12 weeks. Table 4 below summarizes the experimental conditions for each experimental group.

Classification of experimental group Processing contents Naive Oral administration of vehicle once a day along with regular dietary feed Control Oral administration of vehicle once a day along with high fat feed Control(+) A commercial ginkgo leaf extract product (manufacturer: GNC Holdings, Inc., US) is suspended in a vehicle and administered orally once a day at a dose of 173 mg/kg (weight) along with high fat feed. ACG-1 extract 75 Along with feeding high fat feed, the complex extract of Preparation Example 4 was suspended in a vehicle and administered orally once a day at a dose of 75 mg/kg (weight) ACG-1 extract 150 Along with feeding high fat feed, the complex extract of Preparation Example 4 was suspended in a vehicle and administered orally once a day at a dose of 150 mg/kg (weight)

* Vehicle: distilled water

(2) weight gain

The weight of the experimental animals was measured every day during the entire experiment period, and based on this, the weight gain for 12 weeks was calculated. Figure 3 shows the weight gain in the experimental results using the obesity induction animal model. In addition, the weight gain among the results of the obesity-induced animal model experiment is shown in Table 5 below.

Classification of experimental group Weight gain (g/12 weeks) Naive 8.5 Control 19.2 Control(+) 14.1 ACG-1 extract 75 19.0 ACG-1 extract 150 15.5

As shown in Table 5, the composite extract prepared in Preparation Example 4 exhibited excellent anti-obesity effect.

(3) Plasma triglycerides and cholesterol

After the end of the experiment using an obesity-inducing animal model, triglyceride, total cholesterol, and LDL cholesterol content in the plasma of the mouse were measured using an automatic serum analyzer (Komelab 20XT, Thermo Electron, Louisville, CO, USA). Figure 4 shows the content of triglycerides in plasma among the experimental results using the obesity-inducing animal model, Figure 5 shows the total cholesterol content in the plasma of the experimental results using the obesity-inducing animal model, and Figure 6 is It shows the LDL cholesterol content in plasma among the experimental results using the model. As shown in FIGS. 4 to 6, the composite extract prepared in Preparation Example 4 exhibited excellent triglyceride lowering effect, total cholesterol lowering effect, and LDL cholesterol lowering effect.

Increased total cholesterol is known to be an important factor in causing cardiovascular diseases such as high blood pressure. In addition, HDL cholesterol is known to be effective in improving and preventing arteriosclerosis by making cholesterol esters accumulated in peripheral tissues or blood into cholesterol esters and transporting them to the liver, thereby reducing the cholesterol content in the blood, but the LDL cholesterol content It represents an inverse correlation relationship. Therefore, it was confirmed through an experiment that the composition containing the complex extract prepared in Preparation Example 4 of the present invention as an active ingredient can prevent, improve or treat obesity as well as prevent, improve and treat hyperlipidemia, arteriosclerosis, etc. Could

6. Preparation of pharmaceutical composition

<6-1> Preparation of powder

2 g of complex extract of Preparation Example 4

1 g lactose

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

<6-2> Preparation of tablets

100 mg of complex extract of Preparation Example 4

Corn starch 100 mg

100 mg lactose

Stearic acid magnet 2mg

After mixing the above ingredients, tablets were prepared by tableting according to a conventional tablet preparation method.

<6-3> Preparation of capsules

100 mg of complex extract of Preparation Example 4

Corn starch 100 mg

100 mg lactose

2 mg of magnesium stearate

After mixing the above ingredients, a gelatin capsule was filled according to a conventional capsule preparation method to prepare a capsule.

<6-4> Preparation of ring

1 g of complex extract of Preparation Example 4

1.5 g lactose

1 g glycerin

0.5 g xylitol

After mixing the above ingredients, it was prepared so as to be 4 g per ring according to a conventional method.

<6-5> Preparation of granules

150 mg of complex extract of Preparation Example 4

Soybean extract 50 mg

200 mg of glucose

Starch 600 mg

After mixing the above ingredients, 100 mg of 30% ethanol was added and dried at 60°C to form granules, and then filled into a cloth.

<6-6> Preparation of injection

100 mg of complex extract of Preparation Example 4

Sodium metabisulfite 3.0 mg

0.8 mg methylparaben

Propylparaben 0.1 mg

Proper amount of sterile distilled water for injection

After mixing the above ingredients, 2 ml of the two were filled into ampoules and sterilized to prepare an injection.

7. Preparation of food composition

<7-1> Preparation of flour food

0.5 to 5.0 parts by weight of the composite extract of Preparation Example 4 was added to 100 parts by weight of flour, and bread, cakes, cookies, crackers and noodles were prepared using this mixture.

<7-2> Preparation of soup and gravy

0.1 to 5.0 parts by weight of the complex extract of Preparation Example 4 was added to soups and juices to prepare health-promoting meat products, noodle soups, and juices.

<7-3> Preparation of ground beef

10 parts by weight of the complex extract of Preparation Example 4 was added to 100 parts by weight of ground beef to prepare a health-promoting ground beef.

<7-4> Manufacture of dairy products

5 to 10 parts by weight of the composite extract of Preparation Example 4 were added to 100 parts by weight of milk, and various dairy products such as butter and ice cream were prepared using the milk.

<7-5> Manufacturing of Seonsik

Brown rice, barley, glutinous rice, and adlay were gelatinized by a known method, dried, and then roasted, and then prepared into a powder having a particle size of 60 mesh with a grinder.

Black soybeans, black sesame seeds, and perilla seeds were also steamed and dried by a known method, and then roasted, and then prepared into powder having a particle size of 60 mesh with a grinder.

The grains, seeds, and the composite extract of Preparation Example 4 prepared above were mixed in the following ratio to prepare.

Grains (30 parts by weight of brown rice, 15 parts by weight of barley, 20 parts by weight of barley),

Seeds (perilla 7 parts by weight, black beans 8 parts by weight, black sesame 7 parts by weight),

Complex extract of Preparation Example 13 (3 parts by weight),

Ganoderma lucidum (0.5 parts by weight),

Rehmannia (0.5 parts by weight)

<7-6> Manufacture of health drinks

Subsidiary materials such as liquid fructose (0.5g), oligosaccharide (2g), sugar (2g), salt (0.5g), water (75g) and 5 g of the complex extract of Preparation Example 4 are homogeneously mixed and sterilized immediately, It was prepared by packaging in a small container such as a glass bottle or a plastic bottle.

<7-7> Preparation of vegetable juice

Vegetable juice was prepared by adding 5 g of the complex extract of Preparation Example 4 to 1,000 ml of tomato or carrot juice.

<7-8> Preparation of fruit juice

A fruit juice was prepared by adding 1 g of the complex extract of Preparation Example 4 to 1,000 ml of apple or grape juice.

As described above, the present invention has been described through the above embodiments, but the present invention is not necessarily limited thereto, and various modifications may be possible without departing from the scope and spirit of the present invention. Accordingly, the scope of protection of the present invention should be construed as including all embodiments falling within the scope of the claims appended to the present invention.

Claims (15)

As a composition comprising a complex extract consisting of Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract as an active ingredient,
The extraction solvent of the Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract is selected from hot water or hydrous ethanol,
A food composition for improving blood circulation, characterized in that in the complex extract, the weight ratio of Cham Angelica extract, Baekshou extract and Ginkgo biloba extract is 1: (0.5-2): (0.5-2).
The food composition for improving blood circulation according to claim 1, wherein the extraction solvent of the Angelicae extract, Baekshou extract and Ginkgo biloba extract is hydrated ethanol having an ethanol concentration of 50 to 90% (v/v).
delete As a composition comprising a complex extract consisting of Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract as an active ingredient,
The extraction solvent of the Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract is selected from hot water or hydrous ethanol,
In the complex extract, the weight ratio of Angelica Angelica extract, Baekshou extract, and Ginkgo biloba extract is 1: (0.5-2): (0.5-2),
Arterial thrombosis, venous thrombosis, pulmonary arterial embolism, chronic venous ischemia, varicose veins, deep vein thrombosis, arteriosclerosis, cerebral hemorrhage, stroke, and a pharmaceutical composition for use for preventing or treating any one or more thrombotic diseases selected from the group consisting of.
The pharmaceutical composition according to claim 4, wherein the extraction solvent of the Angelicae extract, Baekshou extract and Ginkgo biloba extract is hydrous ethanol having an ethanol concentration of 50 to 90% (v/v).
delete delete As a composition comprising a complex extract consisting of Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract as an active ingredient,
The extraction solvent of the Angelica Angelica extract, Baekshou extract and Ginkgo biloba extract is selected from hot water or hydrous ethanol,
In the complex extract, the weight ratio of Angelica Angelica extract, Baekshou extract, and Ginkgo biloba extract is 1: (0.5-2): (0.5-2),
Arterial thrombosis, venous thrombosis, pulmonary arterial embolism, chronic venous ischemia, varicose veins, deep vein thrombosis, arteriosclerosis, cerebral hemorrhage, stroke, and a food composition for use for preventing or improving any one or more thrombotic diseases selected from the group consisting of.
The food composition according to claim 8, wherein the extraction solvent of the Angelicae extract, Baekshou extract and Ginkgo biloba extract is water-containing ethanol having an ethanol concentration of 50 to 90% (v/v).
delete delete delete delete delete delete

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