KR20210057889A - Food therapy Jeho-Tang composition for enhancing blood circulation - Google Patents

Abstract

The composition of the present invention uses Gwakhyang, excluding excess and sandalwood, which cannot be used as food, while exhibiting an effect equal to or more than the blood circulation improvement effect of Gagamjehotang including Omae, Dead, Excess and Sandalwood, or And it can be industrialized into foods, beverages, and pharmaceuticals by using sugar citrons.

Description

Food therapy Jeho-Tang composition for enhancing blood circulation}

The present invention relates to a composition for improving blood circulation, and more particularly, a food composition for preventing or ameliorating thrombosis disease by improving blood circulation, comprising a food composition for improving blood circulation, and for preventing or treating thrombotic diseases by improving blood circulation. It relates to a pharmaceutical composition for use.

Jeho-tang is included in the Uibang Yuchwi written during the King Sejong period, Heo Gyun's prose collection, the Forest Economy, an encyclopedia of agriculture and forestry, and the Dongguk Tax Period, which records events and customs, and the family encyclopedia. The method of making, efficacy, and eating are detailed in the emergency prescription, which is summarized in a brief summary. Records about Jeho-tang are coming out in the Annals of the Joseon Dynasty, the Seungjeongwon Diary, and the registration of nonbyeonsa.

As a result of reviewing the literature of Jehotang, the word “jeho” was used as a sign of Buddhahood, and in Buddhism, it was used to mean a wise person, as well as to be wise like Shakyamuni, and it also meant a drink with good taste. The fermentation of milk into cheese is called the title, and it is used to mean that it tastes very good. Before Donguibogam, it is listed in the first medical book of Korea, and the defense prescription was referenced, so it can be seen that the prescription came from China. Jehotang was used in the palace as a medicine to relieve the heat and stop thirst, and it was used as a gift given to the servants at Giroso in the sense of the king's good health in the summer in the customs of a single dress day. This is because Jehotang appeared in various contents in the records of the Joseon Dynasty, which are important official records of the Joseon Dynasty, the Annals of the Joseon Dynasty, and the Seungjeongwon Diary. In addition, the fact that the ingredients and methods of making Jehotang were not included in the rural life encyclopedia, the Forest Economy, and the Women's Encyclopedia, Gyuhap Series, suggest that Jehotang was understood as both a drug and a food in the early 17th~18c. As Jehotang was given to the family of the son-in-law at the royal court, it would have been naturally imitated and eaten in a private house. The reason is that it has not only health functions to overcome the heat of the summer, but also tastes good, so it is believed that popularization would have been made easily. The ingredients and methods of making Jehotang, which are recorded in ancient literature, are passed down in modern cooking books as it is a food that can find the origin of Korean herbal medicine mobilization.

Traditional Jehotang like this uses medicinal materials consisting of omae, excess, sandalwood, and cod, but it is difficult to industrialize them into foods and beverages as ingredients that are not listed in the food code and cannot be used as ingredients of food and beverages. There is this.

On the other hand, the traditional method of making Jehotang is to use a powder made by burning straw with the seeds removed from plums, mixed with honey and mixed with honey and made overnight. In addition to the problem of not being able to finely grind the powder, the traditional bath method has a problem that takes a lot of time, making it difficult to mass-produce.

Korean Patent Publication No. 10-2008-0071730 Korean Patent Registration No. 10-1897629

It is an object of the present invention to solve the above-described problems, and to exclude excess and sandalwood, which cannot be used as food, while exhibiting an effect equal to or more than the blood circulation improvement effect of traditional Jehotang including omae, dead, excess and sandalwood. It is intended to provide a composition for improving blood circulation that can be industrialized into foods, beverages, and medicines by including or including gwakhyang and sugar citron together.

Another object of the present invention is that unlike the traditional jehotang manufacturing method, there is no need to finely grind cucumbers and prepare them into powder, and since the process of boiling water for a long time can be omitted, it is suitable for mass production and is advantageous for industrialization into foods and beverages. It is to provide a method for preparing a jehotang composition.

According to one aspect of the present invention,

Omae; sign; And gwakhyang; there is provided a food composition for preventing or improving thrombosis disease by improving blood circulation containing a mixed extract comprising as an active ingredient.

The mixed extract may further include sugar citron.

The mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron.

The mixed extract may be extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof.

The thrombotic disease may be any one selected from the group consisting of atherosclerosis, cerebral hemorrhage, stroke, and cerebral infarction.

According to another aspect of the present invention,

Omae; sign; And gwakhyang; there is provided a beverage composition for preventing or improving thrombosis disease by improving blood circulation containing a mixed extract comprising as an active ingredient.

The mixed extract may further include sugar citron.

The mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron.

The beverage composition may include a honey mixture in which 1 to 8 times the volume of honey is mixed with respect to the mixed extract.

The beverage composition may be a mixture of 5 to 15 times the volume of water with respect to the honey mixture.

According to another aspect of the present invention,

Omae; sign; And Gwakhyang; There is provided a pharmaceutical composition for preventing or treating thrombosis disease by improving blood circulation containing a mixed extract comprising as an active ingredient.

The mixed extract may further include sugar citron.

The mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron.

The mixed extract may be extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof.

The thrombotic disease may be any one selected from the group consisting of atherosclerosis, cerebral hemorrhage, stroke, and cerebral infarction.

According to another aspect of the present invention,

Omae; sign; And Gwakhyang; Method for preparing a food composition for preventing or improving thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof Is provided.

The mixed medicine may further include sugar yuja roll.

According to another aspect of the present invention,

Omae; sign; And Gwakhyang; Method for preparing a beverage composition for preventing or improving thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof Is provided.

The mixed medicine may further include sugar yuja.

The manufacturing method of the beverage composition,

(a) Omae; sign; Kwak Hyang; And sugar yuja; preparing a hot water extract by adding and extracting hot water of 3 to 10 times the volume of the mixed medicine to a mixed medicine containing;

(b) preparing a concentrate by concentrating the hot water extract under reduced pressure to a volume of 1/3 to 1/7 times;

(c) preparing a honey mixture by mixing 2 to 7 times the volume of honey of the concentrate; And

(d) preparing a beverage composition by mixing 5 to 15 times the volume of water of the honey mixture.

According to another aspect of the present invention,

Omae; sign; And Gwakhyang; Method for producing a pharmaceutical composition for preventing or treating thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof Is provided.

The mixed medicine may further include sugar yuja.

The dietary jehotang composition of the present invention exhibits an effect equal to or more than the blood circulation improvement effect of the traditional jehotang including omae, sinus, excess and sandalwood, while excluding excess and sandalwood, which cannot be used as food, and includes gwakhyang, or It can be industrialized into foods, beverages, and pharmaceuticals by including gwakhyang and sugar citron together.

In addition, the production method of the food preparation hot-tang composition of the present invention is another object of the present invention, unlike the traditional preparation method of making hot-tang, it is not necessary to finely grind the omelet into powder, and the process of bathing for a long time can be omitted, so mass production It is suitable for industrialization such as food and beverage.

1 is a flowchart sequentially showing an example of a method of manufacturing a beverage composition for preventing or improving thrombosis by improving blood circulation of the present invention.
Figure 2 is a photograph of the manufacturing process of the food preparation hot water beverage according to Example 1.
3 shows the results of analyzing the blood clot inhibitory efficacy of a single material according to Experimental Example 1.
4 shows the results of a cytotoxicity test of a single material according to Experimental Example 2.
5 shows the results of analyzing the blood clot inhibition efficacy of the composite material according to the comparison of the MA value of Experimental Example 3.
6 shows the results of analyzing the blood clot inhibitory efficacy of the composite material according to the comparison of the LY30 value of Experimental Example 3.
7 is a cytotoxicity test result of the composite material according to Experimental Example 4.
8 is a comparative analysis result of HPLC chromatograms according to Experimental Example 6.
9A and 9B are results of comparative analysis of LC/MSMS chromatograms according to Experimental Example 6.

Hereinafter, the present invention will be described in detail.

The composition for improving blood circulation of the present invention is Omae; sign; And Gwakhyang; contains a mixed extract containing as an active ingredient, the mixed extract may further include sugar citron.

Omae (烏梅, Prunus) mume ) is dried by collecting the immature fruits of plum trees and fumigation in a non-smoky straw. It has a warm nature, no poison, and sour taste. It can be used to quench walls, to stop vomiting, thirst, and dysentery, and to use alcohol poisoning. It is mainly used for upper limit and coarseness. It is known to treat black warts and to treat frequent spitting with dry mouth.

Sine (砂仁, Amomum Xnthioides ) are warm in nature, taste very good, and are non-toxic. It is known that it evens the inside, lowers energy, stops diarrhea and dysentery, boosts appetite, and improves digestion.

Gwakhyang (藿香, Agastache rugosa ) is the above-ground part of baechohyang and is also called Togwakhyang (土藿香) and Baechohyang (排草香). It is above ground, and the stem is square and about 0.5cm in diameter. The outer surface is dark brown, with vertical patterns and nodes, and 3~10cm between the nodes. The quality is light and soft, and the broken side is uneven, fibrous, and hollow. The upper side of the leaf is green to dark green, and the lower side is yellow-green to grayish brown, and it is shallow deep when viewed from the open. Sometimes a flower stalk is attached. It has a peculiar scent, and the taste is calm and a little cool.

Dang yuja (唐柚子, Citrus maxima ) is a term for the dang citrus tree or its fruit. It is distributed in Jeju Island, Korea, and looks similar to citron, but unlike citron, it is a kind of pomelo. In Jeju language, it is called Dengyuji.

The extraction solvent for extracting the mixed extract is water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether, or a mixed solvent thereof. The lower alcohol may include 20 to 80% of methanol, ethanol, butanol or propanol.

The extraction solvent is not particularly limited, but it is preferably an extract extracted with water or an aqueous solution of 60 to 80% ethanol.

The term'extract' as used herein refers to crude extract obtained by treating an extraction solvent, as well as omae; sign; And gwakhyang; a mixed extract containing, or a processed product of a mixed extract further including sugar citron in the mixed extract. For example, Ohmae; sign; And Gwakhyang; or the mixed extract including sugar citron in the mixed extract may be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze drying or spray drying.

In addition, Omae of the present invention; sign; And Gwakhyang; The mixed extract containing, or the mixed extract further comprising a sugar citron to the mixed extract is a processed product formulated to be administered to an animal in a broad sense, such as Omae; sign; Kwak Hyang; And it has the meaning of including the powder of sugar yuja. Although in the present invention, ohmae; sign; And Gwakhyang; Although the experiment was conducted with a mixed extract including, or a mixed extract including sugar citron in the mixed extract, it will be expected by those skilled in the art that the desired effect can be achieved even in the same form as the processed product. .

Meanwhile, in the present specification, the term “including as an active ingredient” means “Omae”; sign; And Gwakhyang; It means to contain an amount sufficient to achieve the efficacy or activity of the mixed extract containing, or the mixed extract further comprising sugar citron in the mixed extract. For example, the ohmae; sign; And Gwakhyang; The mixed extract containing, or the mixed extract further comprising a sugar citron to the mixed extract is used in a concentration of 10 to 1500 ㎍ / ㎖, preferably 100 to 1000 ㎍ / ㎖. Omae; sign; And gwakhyang; the mixed extract containing sugar citron added to the mixed extract, or the mixed extract containing sugar citron as a natural product, since there is no side effect to the human body even when an excessive amount is administered as a natural product, the omae contained in the composition of the present invention; sign; And Gwakhyang; The upper limit of the quantity of the mixed extract including, or the mixed extract further including sugar citron in the mixed extract can be carried out by selecting within an appropriate range by a person skilled in the art.

The present invention is Omae; sign; It provides a food composition for preventing or improving thrombosis disease by improving blood circulation, containing a mixed extract containing as an active ingredient.

The mixed extract may further include sugar citron. Preferably, the mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron.

The mixed extract may be extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof.

The thrombotic disease may be arteriosclerosis, cerebral hemorrhage, stroke, and cerebral infarction.

Preferably, the beverage composition may include a honey mixture in which 1 to 8 times the volume of honey is mixed with respect to the mixed extract.

The beverage composition may be a mixture of 5 to 15 times the volume of water with respect to the honey mixture, and it is preferable to drink with ice.

The food composition and beverage composition according to the present invention may be formulated in the same manner as the following pharmaceutical composition and used as a functional food or a functional beverage, or may be added to various foods or beverages. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gums, ice creams, vitamin complexes, health supplements. Etc.

Food composition and beverage composition of the present invention as an active ingredient Omae; sign; And Gwakhyang; In addition to the mixed extract containing, or the mixed extract additionally containing sugar citron to the mixed extract, it may include ingredients commonly added during food production, for example, protein, carbohydrate, fat , Nutrients, seasonings and flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the beverage composition of the present invention is made of drinks and beverages, the omae of the present invention; sign; And Gwakhyang; In addition to the mixed extract including, or the mixed extract further including sugar citron, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, honey, and various plant extracts, etc. I can.

The present invention is Omae; sign; And Gwakhyang; Method for preparing a food composition for preventing or improving thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof Is provided. The mixed medicine may further include sugar yuja.

In addition, the present invention Omae; sign; And Gwakhyang; Method for preparing a beverage composition for preventing or improving thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof Is provided. The mixed medicine may further include sugar yuja.

Preferably, the method for preparing the beverage composition may be followed in the following order, with reference to FIG. 1 which is a flowchart sequentially showing an example of a method for preparing a beverage composition for preventing or improving thrombosis by improving blood circulation of the present invention. Let me explain.

First, Ohmae; sign; And Kwak Hyang In the mixed medicine containing; 3 to 10 times the volume of the mixed medicine Hydrothermal By adding and extracting Hydrothermal Prepare the extract (step a).

The mixed medicine is Omae; sign; And Gwakhyang; and Dangyuja here; may be additionally included.

Preferably, the mixed medicine is cut to an appropriate size, based on 100 parts by weight of ome, 1 to 5 parts by weight of a sign; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron; hot water may be extracted in a mixed state, and in some cases, each medicinal material may be separately extracted with hot water and then mixed.

As the hot water, water of 90 to 110°C, preferably about 100°C may be used.

Preferably, the hot water may be extracted by adding 4 to 8 times the volume of the mixed medicine, more preferably about 5 times the volume of hot water.

In addition, preferably, the hot water extract may be repeatedly extracted twice and used by mixing the first extract and the second extract.

The hot water extraction can be performed using a yaktangi to decoct medicinal herbs.

Next, above Hydrothermal The extract is concentrated under reduced pressure to a volume of 1/3 to 1/7 times to prepare a concentrate (step b).

When concentrating under reduced pressure, the concentration temperature is preferably maintained at 40 to 50?, and more preferably at about 45?.

Preferably, the hot water extract is concentrated under reduced pressure to a volume of 1/4 to 1/6 times, and more preferably concentrated under reduced pressure to a volume of about 1/5 times.

Afterwards, the above Concentrate A honey mixture is prepared by mixing 2 to 7 times the volume of honey (step c).

The concentrate and honey are sufficiently mixed and homogenized, and the type of honey can be applied in various ways.

Finally, a beverage composition is prepared by mixing 5 to 15 times the volume of water of the honey mixture (step d).

Preferably, a beverage composition is prepared by mixing 7 to 12 times the volume of water of the honey mixture, and when drinking, ice may be added to maintain the optimum taste.

The present invention is the ohmae; sign; It provides a health functional food and a health functional drink comprising a food composition for improving blood circulation comprising a mixed extract including, or gwakhyang, or a mixed extract further comprising sugar citron in the mixed extract as an active ingredient. What are health functional foods and health functional beverages, Ohmae; sign; And gwakhyang; or a mixed extract containing sugar citron added to the mixed extract, added to food materials such as beverages, teas, spices, gums, confectionery, etc., or prepared by encapsulation, powdering, suspension, etc. As a food, it means that when consumed, it has a specific effect on health, but unlike general drugs, it has the advantage of not having side effects that may occur when taking a drug for a long time by using food as a raw material. The health functional food and health functional beverage of the present invention obtained in this way are very useful because they can be consumed on a daily basis. Omae in such health functional foods and health functional beverages; sign; And Gwakhyang; The amount of the mixed extract containing the mixed extract, or the mixed extract additionally containing sugar citron to the mixed extract can not be uniformly regulated depending on the type of health functional food and health functional beverage to be treated, but food and beverage It may be added within a range that does not impair the original taste, and is usually 0.01 to 50% by weight, preferably 0.1 to 20% by weight, based on the target food and beverage. In addition, in the case of health functional foods in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food and health functional beverage of the present invention may be in the form of pills, tablets, capsules or beverages.

In addition, the present invention Omae; sign; It provides a pharmaceutical composition for preventing or treating thrombotic diseases by improving blood circulation, comprising a mixed extract comprising, as an active ingredient, Kwakhyang.

The mixed extract may further include sugar citron. Preferably, the mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron.

The mixed extract may be extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof.

The thrombotic disease may be arteriosclerosis, cerebral hemorrhage, stroke, and cerebral infarction.

The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, lubricants. Agents or flavoring agents may be used.

For administration, the pharmaceutical composition may contain one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients, and may be preferably formulated into a pharmaceutical composition.

The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, trackcacanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

Acceptable pharmaceutical carriers for compositions formulated as liquid solutions are sterilized and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injection formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, and is usually As such, a skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001-10 g/kg.

The pharmaceutical composition of the present invention may be prepared in unit dosage form by formulation using a pharmaceutically acceptable carrier and/or excipient, or may be prepared by incorporating it into a multi-dose container. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.

The present invention is Omae; sign; And Gwakhyang; Method for producing a pharmaceutical composition for preventing or treating thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof Provides. The mixed medicine may further include sugar yuja.

In addition, the present invention Omae for the manufacture of a drug or food for improving blood circulation; sign; And gwakhyang; provides the use of the mixed extract containing. Omae as described above; sign; And Gwakhyang; The mixed extract containing; may be used for the treatment or improvement of thrombotic diseases caused by improvement of blood circulation. The mixed extract may further include sugar citron.

In addition, the present invention provides an effective amount of a mammal; sign; And it provides a method for preventing or treating thrombosis disease according to improvement of blood circulation comprising administering a mixed extract comprising: gwakhyang. The mixed extract may further include sugar citron.

The term "mammal" as used herein refers to a mammal that is an object of treatment, observation or experiment, and preferably refers to a human.

The term "effective amount" as used herein refers to an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human thought by a researcher, veterinarian, doctor or other clinician, which Or an amount that induces relief of symptoms of the disorder. The effective amount and frequency of administration for the active ingredient of the present invention may be changed according to the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, and general health of the patient. It can be adjusted according to various factors including condition, sex and diet, time of administration, route of administration and rate of secretion of the composition, duration of treatment, and drugs used concurrently. In the prevention, treatment or improvement method of the present invention, in the case of an adult, it is preferable to administer the extract at a dose of 0.001 g/kg to 10 g/kg when administered once to several times a day.

Ohmae in the treatment method of the present invention; sign; And Gwakhyang; The composition comprising a mixed extract comprising as an active ingredient can be administered in a conventional manner through oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, or intradermal routes. I can. The mixed extract may further include sugar citron.

Hereinafter, a preferred embodiment is presented to aid in the understanding of the present invention, but it is obvious to those skilled in the art that various changes and modifications are possible within the scope of the present invention and the scope of the technical idea, but the following examples are only illustrative of the present invention, It is natural that such modifications and modifications fall within the scope of the appended claims.

[ Example : Manufacture of single medicine]

Preparation of concentrated extract of single medicinal herbs

Ingredients were prepared by cutting the medicines of Prunus mume, Amomum Xnthioides, excess, sandalwood, Agastache rugose, and Citrus maxima into appropriate sizes. Each medicinal material is packaged twice in a standard herbal extract bag, added with water 5 times the volume of the medicinal material for 6 hours at 100?, extracted with hot water twice, filtered, and then filtered so that the volume of the sample is 1/5 45? It was concentrated under reduced pressure to prepare a concentrated extract of each single medicinal material.

Experimental example 1: Analysis of antithrombotic efficacy of a single material

In the conventional patent No. 10-2008-0071730 "A composition for improving blood circulation containing Gagamjeho-tang extract as an active ingredient", Gagamjeho-tang is characterized by exhibiting thrombotic inhibitory effects, including oleum, dead, excess, and sandalwood. However, since excess and sandalwood among the four herbal medicinal herbs are not listed in the Food Code and cannot be used as food ingredients, we propose to propose Kwak-hyang and Dang-Yu-ja as candidate materials that can replace them.

First, a blood clot inhibitory effect analysis experiment was performed on the herbal medicine used in the conventional patent, which is a single herbal medicine, and the single material of each of the herbal medicines proposed as candidates, such as Omae, Dead, Excess, Baekdanhyang, Gwakhyang, and Dangyuja. The specific experimental method is as follows.

Six-week-old SD male rats were anesthetized with Avertin and opened, and whole blood was collected from the abdominal aorta. Collected whole blood is transferred to a tube containing Sodium Citrate (BD: Vacutainer Coagulation-glass tube) and shaken by turning it up and down sufficiently to prevent clotting.After that, use a vertical tube rotator to inside the tube. Prevented blood clotting. In a cup for TEG (Thromboelastograph), _{20 µl of CaCl 2} , 9 µl of each single extract of Omae, Sine, Excess, Sandalwood, Kwak-Hyang, and Dangyuja, respectively (stock 100 mg/ml), followed by 331 µl of whole blood, final concentration 2.5 mg/ It was put in ml, and the maximum strength of clot (MA) value was measured using a TEG instrument. The results were averaged with 3 repeated values of MA (Maximum strength of clot), and the results are shown in FIG. 3.

According to this, the maximum coagulation strength of MA (Maximum strength of clot) value was P<0.05 compared to the control group for false, dead, and excess, but showed significant blood clot suppression effect in the case of sandalwood, gwak, and sugar. No efficacy was shown.

Experimental example 2: Cytotoxicity test of a single material

1) Raw264.7 cells

Raw264.7 cells were used in DMEM medium containing 10% fetal bovine serum and 1% penicillin/streptomycin. Cells were cultured in a 37±1° C. incubator containing 5% carbon dioxide and saturated water vapor, and passaged every 2 to 3 days. Raw264.7 cells were seeded in a 96-well plate at 2-4×10 ⁴ per well (200 µl) and cultured for 18-24 hours. After each sample and the positive control were treated, they were reacted for 48 hours in an incubator at 37°C. The CCK-8 solution was added to 20 μl/well of the cell culture solution and reacted in a 37° C. incubator for 1 to 4 hours. After the reaction, absorbance was measured at 450 nm using a microplate reader.

2) HEK293 (kidney cell) cells

HEK293 cells were MEM medium containing 10% fetal bovine serum, 1% penicillin/streptomycin, 1% sodium pyruvate, and 1% MEM NEAA. Cells were cultured in a 37±1° C. incubator containing 5% carbon dioxide and saturated water vapor, and passaged every 3-4 days. HEK293 cells were seeded in a 96-well plate in a ^{number of 2-4×10 4} per well (200 µl) and cultured for 18-24 hours. After each sample and the positive control were treated, they were reacted for 48 hours in an incubator at 37°C. The CCK-8 solution was added 20 µl/well to the cell culture solution and reacted in an incubator at 37° C. for 1 to 4 hours. After the reaction, absorbance was measured at 450 nm using a microplate reader.

Accordingly, toxicity evaluation was performed on each of Omae, Sine, Sandalwood, Excess, Dangyuja, and Kwakhyang, and the results are shown in Tables 1 and 4 below. According to this, IC50 values in Raw264.7 and HEK293 cells were 1 mg/ml or more in all herbal medicines except for sandalwood. That is, Dangyuzawa Kwakhyang proposed as candidate herbal medicines in the present invention did not show cytotoxicity.

number Chinese medicine name Extraction solvent IC50 (mg/ml) Raw264.7 HEK293 One Omae Water extract > 1 > 1 2 sign Water extract > 1 > 1 3 Sandalwood Water extract 0.512 0.477 4 Excess Water extract > 1 > 1 5 Party Water extract > 1 > 1 6 Kwak Hyang Water extract > 1 > 1

[ Example : Composite medicine manufacturing]

Example One: Food preparation hot water Produce

As shown in Table 2 below, the mixed medicinal materials in which Omae, Sine, Gwak Hyang, and Dangyuja were mixed in a weight ratio of 32:1:2:1 were cut into appropriate sizes to prepare ingredients. The mixed medicine is packaged twice in a standard extraction bag of herbal medicine, and water is added 5 times the volume of the mixed medicine for 6 hours at 100℃, extracted with hot water twice, filtered, and then 45℃ so that the volume of the sample becomes 1/5. Concentrated extract was prepared by concentrating under reduced pressure.

Example 2: Food preparation hot water Beverage manufacturing

Figure 2 is a photograph illustrating the manufacturing procedure of the food preparation hot-tang according to Example 1. According to this, the concentrated extract of Jikchijehotang prepared according to Example 1 was mixed with honey by adding 5 times the volume of honey and homogenized with honey, and cold water 7 times the volume of the homogenized concentrate with honey was added and mixed. The beverage was prepared.

Example 3: Party except Food preparation hot water Produce

Except for the sugar yuja was prepared in the same manner as in Example 1 to prepare a food preparation hot-tang beverage.

Comparative example One: Gagamjehotang Produce

Gagamjehotang was prepared in the same manner as in Example 1, except that excess was used instead of gwakhyang and sandalwood hyang was used instead of dangyuja.

Comparative example 2: Gagamjehotang Beverage manufacturing

A beverage was prepared in the same manner as in Example 2, except that Gagamjehotang of Comparative Example 1 was used instead of the dietary hotang of Example 1.

In Table 2 below, the herbal ingredients and contents of Examples 1 to 3, and Comparative Examples 1 and 2 are summarized. Here, since the honey is added after preparing the concentrated extract of the mixed herbal medicine in the food preparation hot-tang beverage of Example 2 and the Gagamje hot-tang beverage of Comparative Example 2, the content display is omitted because it cannot be compared with the herbal medicine weight.

Herbal medicine mixing ratio Example 1
(Food-based hot water bath) Example 2
(Food-based hot water drink) Example 3
(Excluding the party owner
Food supplement hot water) Comparative Example 1
(Gagamjehotang) Comparative Example 2
(Gagamjehotang
beverage) 32 (100 parts by weight) Omae Omae Omae Omae Omae 1 (3.125 parts by weight) sign sign sign sign sign 2 (6.25 parts by weight) Kwak Hyang Kwak Hyang Kwak Hyang Excess Excess 1 (3.125 parts by weight) Party Party - Sandalwood Sandalwood - - honey - - honey

Experimental example 3: Analysis of blood clot suppression efficacy of composite materials

Excluding excess and sandalwood, which cannot be used as food materials among the conventional Gagamjehotang's ome, dead, excess, and sandalwood, a complex herbal medicine was prepared by adding at least one of Kwakhyang and Dangyuja, which are new materials, and has the effect of inhibiting blood clots thereon. Analyzed.

Instead of a single herbal extract, cucumber + sine + excess + sandalwood = 32:1: 2: 1 parts by weight of mixed extract (Comparative Example 1), cucumber + sine + sugar citron = 32: 1 parts by weight of mixed extract, cucumber + sine + Gwakhyang = 32:1:2 parts by weight of mixed extract (Example 3), Omae + sine + Gwakhyang + sugar citron = 32:1: 2: 1 parts by weight of mixed extract (Example 1) was used except that the experiment The blood clot inhibition efficacy analysis was performed in the same manner as in Example 1, and the results are shown in FIG. 5.

Accordingly, looking at the MA value of the mixed extract compared to the control group, the mixed extract treated with Omae+Sain+Sugar Citron did not show the effect of suppressing blood clots at P<0.05 compared to the control group, but the Omae+Sine+Excess+sandalwood treatment group (Comparative Example) 1: Gagamjehotang), Omae + Sain + Gwakhyang treatment group (Example 3: Mealjehotang excluding sugar citron), and Omae + Sain + Gwak Hyang + Dang Citron treatment group (Example 1: Mealchijehotang), P<0.05 compared to the control group. It was found that the blood clot inhibitory effect was significantly increased.

On the other hand, looking at the MA value of the mixed extract based on Omae, Omae + Sine + Sugar Citron treatment group did not show a significant thrombus inhibition effect at P<0.05, but Omae + Sine + Excess + Sandalwood treatment group (Comparative Example 1: Gagamjehotang), Omae + Sain + Gwakhyang treatment group (Example 3: Mealjehotang excluding sugar citron), and Omae + Sain + Gwakhyang + Dang Citron treatment group (Example 1: Mealchijehotang) were significant at P<0.05 compared to Omae It could be confirmed that it exhibits the blood clot suppression effect.

In other words, the food jehotang of Example 1 of the present invention and the food jehotang of Example 3 excluding sugar yuja are similar to the Gagamjehotang of Comparative Example 1 containing ingredients that cannot be used in conventional foods, and are of significance based on the control and Omae It could be confirmed that it exhibits the blood clot suppression effect.

Next, a blood clot suppression experiment was performed according to the above-described experimental method, but the samples of Gagamjehotang of Comparative Example 1 and Mealchijehotang of Example 1 were treated respectively, and the LY30 (Percent lysis) value, which is the dissolution rate, was each 3 repeated values. The average was taken and the results are shown in FIG. 6.

According to FIG. 6, it was confirmed that LY30 (%) was increased to P<0.05 in Gagamjehotang of Comparative Example 1 compared to the control, and to P<0.05 compared to Gagamjehotang in Example 1 I did. In view of these results, it was found that the effect of inhibiting blood clots as well as the blood clot dissolution efficacy of Jikchijehotang of Example 1 was superior to that of the conventional Gagamjehotang.

Experimental example 4: Cytotoxicity test of composite materials

Cytotoxicity experiments were performed on Raw264.7 cells and HEK293 cells for the Shikchijehotang of Example 1 and the Gagamjehotang of Comparative Example 1, and the experimental method was the same as that of Experimental Example 2.

The results of the cytotoxicity evaluation of Shikchijehotang of Example 1 and Gagamjehotang of Comparative Example 1 are shown in Table 3 and FIG. 7 below. According to this, it was determined that the IC50 value in Raw264.7 and HEK293 cells was 1 mg/ml or more, and thus did not show cytotoxicity.

division Chinese medicine name Extraction solvent IC50 (mg/ml) Raw264.7 HEK293 Example 1 Food preparation hot water - > 1 > 1 Comparative Example 1 Gagamjehotang - > 1 > 1

Experimental example 5: Animal toxicity test of composite materials

Repeated toxicity evaluation for 1 week and 4 weeks was performed, and the test substance was prepared in Example 1 according to the “Regulation on the recognition of functional ingredients and standards for health functional foods and standards (No. 2013-217)” notified by the Ministry of Food and Drug Safety. Animal toxicity was evaluated for Gagamjehotang and Comparative Example 1, and the evaluation conditions are as follows.

-Test animal: Sprague-Dawley/Crl:CD (SD) rat (no specific pathogen (SPF))

-Week-age range: Obtained at about 5 weeks of age, and animals are about 6 weeks old at the start of administration

-Individual identification: Color marking, Tail tattoo, Cage card

-Histopathological examination: Histopathological examination was not performed as no suspicious changes in the toxicity of the test substance were observed in general symptom observation, clinical pathological examination, organ weight, and gross findings.

1) Results of repeated oral administration for 1 week

To male rats, the dietary supplement of Example 1 was administered orally at a dose of 0, 1000, 2000 and 5000 mg/kg/day, and the Gagamjehotang of Comparative Example 1 was orally administered at a dose of 2000 and 5000 mg/kg/day for 1 week. The experimental conditions are shown in Table 4 below. According to this, no dead animals were observed during the test period, and no change by administration of the test substance was observed in all sections except some hematology and organ weight changes. Based on this, the high dose of the 4-week repeated oral toxicity test was performed at 5000 mg/kg/day or less.

Test group gender Population Animal ID Volume
(Ml/kg) Dose
(mg/kg/day) Vehicle control Male 5 01-05 10 0 Example 1: Food preparation hot water Male 5 06-10 10 1000 Example 1: Food preparation hot water Male 5 11-15 10 2000 Example 1: Food preparation hot water Male 5 16-20 10 5000 Comparative Example 1: Gagamjehotang Male 5 21-25 10 2000 Comparative Example 1: Gagamjehotang Male 5 26-30 10 5000

2) Results of repeated oral administration for 4 weeks

In male and female rats, the dietary jehotang of Example 1 at 0, 1000, 2000 and 5000 mg/kg/day doses, and the Gagamjehotang of Comparative Example 1 at 2000 and 5000 mg/kg/day doses for 4 weeks orally After administration, a two-week recovery test was performed, and the experimental conditions are shown in Table 5 below. According to this, toxicity was not observed in the food preparation hotang of Example 1.

Test group gender Population Animal ID Volume
(mL/kg) Dose
(mg/kg/day) Main Recovery Vehicle control Male
Female 15
15 1-10
76-85 11-15
86-90 10 0 Example 1: Mealchijehotang Male
Female 10
10 16-25
91-100 - 10 1000 Example 1: Mealchijehotang Male
Female 10
10 26-35
101-110 - 10 2000 Example 1: Mealchijehotang Male
Female 15
15 36-45
111-120 46-50
121-125 10 5000 Comparative Example 1:
Gagamjehotang Male
Female 10
10 51-60
126-135 - 10 2000 Comparative Example 1:
Gagamjehotang Male
Female 15
15 61-70
136-145 71-75
146-150 10 5000

Experimental example 6: Physicochemical analysis

The physicochemical analysis was performed as follows.

1) HPLC DAD pattern analysis

HPLC analysis conditions of Gagamjehotang of Comparative Example 1 and Shikchijehotang of Example 1 are as follows. The HPLC system was Shimadzu LC-20AD PDA, and the column used for the analysis was YMC Triat C18 150mm × 4.6mm, S-3, 12nm. The temperature of the column oven was maintained at 40° C., and the flow rate was maintained at 0.5 ml/min. As a solvent, tertiary distilled water (A) and Acetonitrile (B) containing 0.1% formic acid were used, and the solvent gradient over time is shown in Table 6 below.

Time (Min) Solvents (B)% 0.01 One 10 5 25 20 30 20 60 50 80 100 100 100

2) LC-MS/MS pattern analysis

LC-MS/MS analysis conditions of Gagamjehotang of Comparative Example 1 and Shikchijehotang of Example 1 are as follows. The LC-MS/MS System used Waters SYNAPT G2 Si HDMS QTOF High-resolution tandem mass spectrometer combined with Waters UPLC system. The column used for the analysis was an ACQUITY UPLC HSS T3 column (100　mm　×　2.1　mm, 1.8　μm, Waters). The temperature of the column oven was maintained at 40° C., and the flow rate was maintained at 0.5 mL/min. As the solvent, tertiary distilled water (A) containing 0.1% formic acid and Acetonitrile (B) containing 0.1% formic acid were used, and the solvent gradient over time is shown in Table 7 below.

Time (Min) Solvents (B)% 0.01 3 5 100 16 100

The molecular weight of the derivative compounds passing through the column was measured in the positive and negative ion modes, and the capillary voltage and cone voltage were set to 2 kV and 40 V, respectively, in the positive mode, and 1 kV and 40 V, respectively, in the negative mode. The scan range was set to 50 to 1200 Da, and the scanning time was set to 0.2 seconds. All molecular ions were fragmented at 20-40 eV, and information of all fragmented ions was collected every 0.2 seconds.

The HPLC chromatograms of Gagamjehotang of Comparative Example 1 and Shikchijehotang of Example 1 are shown in FIG. 8, (a) is the HPLC chromatogram of Gagamjehotang of Comparative Example 1, and (b) is the HPLC of Example 1 Shikchijehotang. It shows the chromatogram.

According to this, four major peaks were specifically observed at 19.8 minutes, 26.4 minutes, 30.8 minutes, and 38.4 minutes in both Gagamjehotang of Comparative Example 1 and Jikchijehotang of Example 1. However, unlike Gagamjehotang, 4 types of miner peaks could be observed between 44 and 55 minutes in Sikchijehotang, which is believed to be derived from the constituents of Gagamjehotang and Sikchijehotang.

Meanwhile, LC-MS/MS chromatograms of Gagamjehotang of Comparative Example 1 and Shikchijehotang of Example 1 are shown in FIGS. 9A and 9B, respectively. Here, FIG. 9A is an LC-MS/MS chromatogram of Gagamjehotang in Comparative Example 1, and FIG. 9B is an LC-MS/MS chromatogram of Gagamjehotang in Example 1.

According to this, in both Gagamjeho-tang of Comparative Example 1 and Shikchijeho-tang of Example 1, peaks having RT of the same time at 2.90 minutes, 3.38 minutes, 3.48 minutes, 3.59 minutes, and 3.69 were confirmed in a diode array chromatogram. In the positive and negative total ion chromatograms analyzed by MS, 239.1491 (Pirimicarb ^* MS/MS library prediction), 163.0396 (Umbelliferone) [M+H] ⁺ , 353.1501 (Mitraphyllic acid) [M+H] ^- the peak that was observed, in 3.43 minutes 739.1887 (Menthoside) [M + H ] - in, 3.54 minutes in 365.1573 (Citrusin C) [M + H] + was a peak is observed, and 3.65 minutes 571.1692 (Mudanpioside E) [M +H] ^-, peaks of 409.1832 (Apocynoside) [M+H] ⁺ were observed at 3.77 min. The peak of Gagamjehotang and Shikchijehotang was observed at 5.06 minutes, 605.3712 (Periplocoside M) [M+H] ⁺ was observed. In Shikchijehotang, 362.2215, which was distinguished from Gagamjehotang at 4.97, 5.22 and 6.16 minutes. (Disopyramide) [M+H] ⁺ , 649.3949 (Periplocoside O) [M+H] ⁺ , 447.1287 (Rhamnocitrin-3-O-rhamnoside) [M+H] ⁺ were observed, respectively. From the above results, the structure can be inferred according to the molecular weight of the constituents of Gagamjeho-tang and Sikchijeho-tang and the MS/MS library corresponding thereto.

Experimental example 7: sensory evaluation

The taste and preference evaluation of the Gagamjehotang drink of Comparative Example 2 and the foodstuff hotang drink of Example 2 is an advantage comparison method. A survey was conducted. In this case, the higher the score, the higher the preference for taste. The results were obtained using the SPSS (Statistics Package for the Social Science, Ver. 24.0 for Window) package to obtain the mean and standard deviation. The statistical significance difference was verified at p<0.05 through ANOVA, Duncan's multiple range test, and chi-square test. The resulting sensory evaluation results are summarized in Table 8 below.

age
Kinds Evaluation of taste 10 units 20's 30s 40-50 generations Over 60 Comparative Example 2:
Gagamjehotang Beverage 3.77±0.89a 3.93±0.83b 4.12±0.66c 4.11±0.75c 4.17±0.83c Example 2:
Food-based hot water drink 4.20±0.87a 4.12±0.79a 4.14±0.67a 4.12±0.68a 4.20±0.65a

According to this, it was found that the Gagamjehotang beverage of Comparative Example 2 had a higher evaluation score for taste as the age group was higher, whereas the dietary hottang beverage of Example 2 was highly evaluated at all ages.

In the above, embodiments of the present invention have been described, but those of ordinary skill in the relevant technical field add, change, delete or add components within the scope not departing from the spirit of the present invention described in the claims. It will be possible to variously modify and change the present invention by means of the like, and it will be said that this is also included within the scope of the present invention.

Claims (22)

Omae; sign; And Gwakhyang; Food composition for preventing or improving thrombosis disease by improving blood circulation containing a mixed extract comprising as an active ingredient. The method of claim 1,
The mixed extract is a food composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it further comprises a sugar citron. The method of claim 2,
The mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron; Food composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it comprises. The method of claim 1,
The mixed extract is a food composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it is extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof. The method of claim 1,
The thrombotic disease is any one selected from the group consisting of arteriosclerosis, cerebral hemorrhage, stroke, and cerebral infarction. Omae; sign; And Gwakhyang; Beverage composition for preventing or improving thrombosis disease by improving blood circulation containing a mixed extract comprising as an active ingredient. The method of claim 6,
The mixed extract is a beverage composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it further comprises a sugar citron. The method of claim 7,
The mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of sine; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron; Beverage composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it comprises. The method of claim 8,
The beverage composition is a beverage composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it comprises a honey mixture in which 1 to 8 times the volume of honey is mixed with respect to the mixed extract. The method of claim 9,
The beverage composition is a beverage composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that 5 to 15 times the volume of water is mixed with the honey mixture. Omae; sign; And Gwakhyang; A pharmaceutical composition for preventing or treating thrombotic diseases by improving blood circulation containing a mixed extract comprising as an active ingredient. The method of claim 6,
The mixed extract is a pharmaceutical composition for preventing or treating thrombosis disease by improving blood circulation, characterized in that it further comprises sugar citron. The method of claim 12,
The mixed extract is based on 100 parts by weight of Omae, 1 to 5 parts by weight of the sign; 3 to 10 parts by weight of Gwak Hyang; And 1 to 5 parts by weight of sugar citron; A pharmaceutical composition for preventing or treating thrombotic diseases by improving blood circulation, characterized in that it comprises. The method of claim 11,
The mixed extract is a pharmaceutical composition for preventing or treating thrombotic diseases by improving blood circulation, characterized in that the extract is extracted with water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof. The method of claim 11,
The thrombotic disease is any one selected from the group consisting of arteriosclerosis, cerebral hemorrhage, stroke, and cerebral infarction. Omae; sign; And Gwakhyang; Method for preparing a food composition for preventing or improving thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, an alcohol having 1-4 carbon atoms, or a mixed solvent thereof . The method of claim 16,
The mixed medicine is a method for producing a food composition for preventing or improving thrombosis disease by improving blood circulation, characterized in that it further comprises sugar yuzarol. Omae; sign; And Gwakhyang; Method for preparing a beverage composition for preventing or improving thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof . The method of claim 18,
The method for producing a beverage composition for preventing or improving thrombosis disease by improving blood circulation, wherein the mixed medicine further comprises sugar citron. The method of claim 19,
The manufacturing method of the beverage composition,
(a) Omae; sign; Kwak Hyang; And sugar yuja; preparing a hot water extract by adding and extracting hot water of 3 to 10 times the volume of the mixed medicine to a mixed medicine containing;
(b) preparing a concentrate by concentrating the hot water extract under reduced pressure to a volume of 1/3 to 1/7 times;
(c) preparing a honey mixture by mixing 2 to 7 times the volume of honey of the concentrate; And
(d) preparing a beverage composition by mixing 5 to 15 times the volume of water of the honey mixture to prepare a beverage composition for preventing or improving thrombotic diseases by improving blood circulation. Omae; sign; And Gwakhyang; Method for producing a pharmaceutical composition for preventing or treating thrombosis disease by improving blood circulation comprising the step of preparing an extract by extracting a mixed medicine containing water, alcohol having 1-4 carbon atoms, or a mixed solvent thereof . The method of claim 21,
The method for producing a pharmaceutical composition for preventing or treating thrombotic diseases by improving blood circulation, wherein the mixed medicine further comprises sugar citron.

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