KR20200014564A - A composition for improving, preventing and treating of asthma and vascular disease - Google Patents

Abstract

The present invention relates to a composition for alleviating, preventing or treating asthma and vascular diseases, which contains a mixture of Cirsium japonicum, Platycodon grandifloras, Codonopsis lanceolata, pear, Petasites japonicus, Luffa cylindrica, Zingiber officinale, and embryo buds of rice as an active component, thereby being able to alleviate, prevent or treat asthma or vascular diseases selected from a group consisting of peripheral vascular obstruction, vascular restenosis, angina pectoris, myocardial infarction, and ischemic heart disease. In addition, since the composition has no toxicity, it is possible to be consumed in a form of food.

Description

Composition for improving, preventing and treating of asthma and vascular disease containing mixtures containing thistle, bellflower, and tortoise

The present invention relates to a composition for improving, preventing or treating asthma and vascular diseases, which contains a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice bran as an active ingredient.

Environmental diseases such as bronchial asthma are known as immune diseases, Th2 cells are well known to play a pivotal role in inducing a bronchial asthma response. When CD4 T cells are stimulated by antigens in lymphocytes, they can be differentiated into several Th cells according to cytokines that are recognized at the same time, and the recognized cytokines are thymic stromal lymphoprotein (TSLP). Or in the case of type 2 cytokines such as IL-4, these cells differentiate into Th2 to induce a bronchial asthma response.

In addition, dendritic cells that provide antigens to CD4 T cells have also been shown to respond to stimulation of TSLP and to help differentiate Th2 cells.

These cytokines include TSLP, IL-25, IL-33, etc. Among them, TSLP is expected to play the most effective role. In addition, it has been found that the inhibition of TSLP secretion in animal models makes Th2 cells difficult to produce and activity, and that animals do not cause disease. It has been done. Taken together, TSLP is an important cytokine that functions both in the differentiation and activation of Th2 cells, and it is recognized that controlling it is important for the treatment of bronchial asthma.

On the other hand, vascular disease is a serious social problem in modern society. According to statistics on the cause of death published by the National Statistical Office in 2010, vascular diseases including hypertension, ischemic heart disease, and cerebrovascular disease were the second leading causes of death in Korea, after malignant tumors. , Women reported a significant increase in mortality from vascular disease at age 65 and older. Atherosclerosis, which accounts for the largest portion of vascular diseases, is known to be a risk factor for age, sex, hypertension, hyperlipidemia, diabetes, smoking, lack of exercise and obesity. Patients with vascular disease receive continuous medication to treat the disease, but it is not easy to cure, and there are side effects due to long-term administration of the medication.

Endothelial (endothelium) is the innermost of all blood vessels, including lymphatic vessels and cardiovascular, and consists of endothelial cells (endothelial cells). Endothelial vessels play a major role in maintaining vascular homeostasis, including vasodilation and contraction, proliferation and migration of vascular smooth muscle, and thrombus formation and dissolution. When the vascular endothelial dysfunction occurs, damage to the blood vessel wall causes vascular diseases such as atherosclerosis.

Atherosclerosis in vascular disease refers to a functional dysfunction in which vascular endothelial cells do not maintain normal homeostasis due to genetic variation, peroxides, hypertension, increased plasma homocysteine concentration, accumulation of lipids in blood vessels, and microbial infection. Lipids such as cholesterol are deposited in the endothelium, which covers the innermost part of blood vessels, hyperproliferation of vascular endothelial cells, formation of atherosclerosis, weakened vascular elasticity, or vascular relaxation as aging progresses. do. As atherosclerosis progresses, vascular endothelial cells undergo vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (IMC-1), monocyte chemoattractant protein-1 (MCP-1), and P-selectin , The expression of adhesion molecules (E-selectin), etc. (adhesion molecules) will be increased, the transformation of low-density lipoproteins in blood, the influx of monocytes or macrophages, and activation into foam cells (foam cells) The triggering process is repeated to promote plaque formation in the blood vessels.

Adherent substances such as VCAM-1, ICAM-1, MCP-1, etc. are known to be activated by a tumor necrosis factor-α (TNF-α), which is one of reactive oxygen species (ROS) or cytokines. (Yen, FL et al., 2013; Mackesy, DZ, 2014).

The adhesion material firmly adheres the cells to the cells to maintain a circular shape and serves to promote adhesion between leukocytes and vascular endothelial cells, leukocytes and extravascular tissue. In addition, leukocytes exit the blood vessels and move to surrounding tissues, increase antigen recognition of T lymphocytes, activate lymphocytes and monocytes in peripheral blood, and further enhance the action of activated lymphocytes. Through various functions as described above, the adhesion substances play an important role in vascular disease.

Republic of Korea Patent No. 1869301 Republic of Korea Patent Publication 2018-0063658

It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of asthma and vascular diseases containing a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice eyes as an active ingredient.

In addition, another object of the present invention to provide a food composition for the prevention or improvement of asthma and vascular diseases containing a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow as an active ingredient.

The pharmaceutical composition for preventing or treating asthma and vascular diseases of the present invention for achieving the above object may contain a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow as an active ingredient.

The thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow are mixed in a weight ratio of 1: 1-3: 1-3: 1-3: 0.4-1: 0.4-1: 0.4-1: 0.4-1 Can be.

The thistle, bellflower, deodeok, pears, coltsfoot, loofah, ginger and rice snow may be an extract extracted in a bath at 80 to 100 ℃ by mixing the respective substances.

The thistle, bellflower, deodeok, pears, coltsfoot, loofah, ginger and rice flakes may be a dough kneaded by mixing the pulverized by mixing the respective materials with water.

The vascular disease may be a disease selected from the group consisting of peripheral vascular obstruction, vascular restenosis, angina pectoris, myocardial infarction and ischemic heart disease.

The thistle may be a mixed extract of a flower, a stem and a leaf, and a root of the milk thistle mixed at a weight ratio of 1: 14-25: 0.1-0.9.

The stem and leaf mixture may be mixed in a weight ratio of 1: 1-4 stem and leaf.

The thistle mixed extract may be after mixing the extract of the extract of the bath in 80 to 100 ℃ by extracting the mixture of the flower of thistle, and the stem and the leaves in a bath at 80 to 100 ℃.

The milk thistle mixed extract may be added to the powder obtained by drying and grinding the remaining residue after extraction of the roots at 80 to 100 ℃.

In addition, the food composition for preventing or improving asthma and vascular diseases of the present invention for achieving the above another object may contain a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow as an active ingredient. have.

The composition for improving, preventing or treating asthma and vascular diseases of the present invention is not toxic and improves, prevents or improves vascular diseases selected from the group consisting of asthma or peripheral vascular obstruction, vascular restenosis, angina pectoris, myocardial infarction and ischemic heart disease. It is very effective in treating and preparing competitive food compositions and pharmaceutical compositions.

The present invention relates to a composition for improving, preventing or treating asthma and vascular diseases, which contains a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice bran as an active ingredient.

Hereinafter, the present invention will be described in detail.

The composition for improving, preventing or treating asthma and vascular diseases of the present invention contains a mixture consisting of thistle, bellflower, reddock, pear, coltsfoot, loofah, ginger and rice bran as an active ingredient.

Thistle

The thistle used in the present invention may be a white thistle (Silybum marianum (L.) Gaertn.), Thistle (Cirsium japonicum Fisch ex DC.var.spinossimum Kitam.) Or a mixture thereof, preferably a white pattern Thistle is to use alone.

The white thistle (Silybum marianum (L.) Gaertn.) Is a deep, shiny green plant with milky leafy veins, and is a long, thin plant that is divided into a wavy, spiny root-leaves at the edges. It is mainly found in embankment fences and abandoned lands. Useful parts of the plant are whole herbs, roots, leaves, seeds, and husks, and thistle seeds contain flavonoid compounds known as silymarin. Thistle seed extract contains 70-80% of silymarin.

Thistle according to the present invention is a mixed extract of a flower, a mixture of stems and leaves, and a root of thistle.

The flower of thistle is purple or red, and its length is 19-24 mm, and it is preferable to use only those having a length of 10 to 15 mm and not longer than that.

In addition, the thistle stem and leaves are used by mixing in a weight ratio of 1: 1-4, preferably 1: 2-3. When the content of the leaf on the basis of the stem is less than the lower limit, the bitter taste may be strong, and when it is above the upper limit, it is not preferable for the effect on asthma and vascular diseases.

In addition, unlike the flowers, stems and leaves harvested twice a year, thistle roots are preferably dried every three years so that they are used after drying.

The flower, stem and leaf mixture, and root of the thistle are mixed in a weight ratio of 1: 14-25: 0.1-0.9, preferably 1: 15-18: 0.3-0.7. If the mixture of the stem and the leaves, and the root content based on the flower is less than the lower limit, the effect on asthma and vascular disease may not be excellent, and when the upper limit is exceeded, the bitter taste is strong and the effect on the asthma and vascular disease Can be lowered.

The mixed extract of the present invention is an extract extracted in bath for 20 to 30 hours, preferably 24 to 28 hours at 80 to 100 ℃. If the boiling water extraction temperature and time is less than the lower limit, the active ingredient may not be extracted. If the boiling water extraction temperature and time is greater than the upper limit, the burnt taste may be strong and the nutrients may be destroyed. In addition, when extraction is performed by other methods such as organic solvent extraction in addition to water bath extraction using water, the effect on asthma and vascular diseases is insignificant, and bitter taste may occur strongly.

Specifically, the mixed extract is a mixture of flowers, a mixture of stems and leaves in a water bath extract, and extract the roots in a separate bath and mix later. Unlike the present invention, the mixture of the flowers, stems and leaves of the mixture and the root of the mixture is extracted in the bath bath, the bitter taste is strong, rather, the effect on asthma and vascular diseases may be lowered.

Specifically, the method for producing thistle includes (A) mixing the flower of the thistle, a mixture of the stem and the leaf, and extracting the water at 80 to 100 ° C. to obtain an extract; (B) extracting the root of thistle at 80-100 ° C. to obtain an extract; And (C) lyophilizing the extracts obtained in the steps (A) and (B), respectively, and powdering and mixing the extracts. In addition, after the step (C), (D) drying and grinding the remaining residue extracted in the step (B); And (E) mixing 100 parts by weight of the powder mixed in the step (C) and 0.1 to 3 parts by weight of the powder of the step (D).

Unlike the steps (A) and (B), when the mixture is extracted with a mixture of flowers, stems and leaves, and roots, the bath is extracted and the bitterness is strong and the effects on asthma and vascular diseases may be lowered; Yield may be lowered when each of the flowers, the mixture of the stem and the leaves, and the roots are extracted in each bath.

When the root residue powder prepared in step (D) is added, the effect on the disease may be significantly improved as compared with the case where the root residue powder is not added.

Rice eyes

The rice eye is the seed of rice, which refers to the nucleus of rice seeds and contains 66% of the nutrition of rice.

In the case of using rice bran or general rice instead of the rice eye, the effect of improving, preventing or treating asthma and vascular diseases may be reduced.

Bellflower

The bellflower is the main ingredient is saponin, the medicinal herb means that the roots are peeled or dried as it is. In oriental medicine, it is used for dentition, lung fever, tonsillitis and diarrhea.

Deodeok

The deodeok contains saponin in abundance, has a bitter taste, and its inherent aroma is very strong. It has various effects such as bronchial disease relief, arteriosclerosis prevention, and blood sugar control.

ship

The pear is about 80% edible part of the fruit, 85-88% moisture, 50 calories calories. As an alkaline food, the main component is carbohydrate and contains 10-13% of sugars (fructose and sucrose), organic acids such as malic acid, tartaric acid and citric acid, vitamins B and C, and fibrin fat. It is effective for bronchial diseases and is good for colds, relieves and asthma, and helps defecation and diuretic effect. Eliminate sputum and cough, relieve symptoms when you have a sore throat, cold or aching stomach, and also help treat boils. In addition, it has a detoxification effect that eliminates hangovers.

coltsfoot

The butterbur is known as an excellent detoxification plant and has the property of purifying and clearing water, and is distributed in Korea and Japan. In addition, butterbur is used as an antitussive agent to stop coughing in oriental medicine.

Scrubbers

The young fruit of the loofah is cooked and eaten for edible use. In traditional medicine in many countries, the loofah's leaves, seeds, and roots are used to treat skin diseases, jaundice, paraplegia, and hemorrhoids. Seeds are toxic and can be used as pesticides. Seed oil can be used for edible or dermatological diseases.

ginger

The ginger treats chills, fever, headache, vomiting, seawater, phlegm caused by cold and is effective for stomach ache due to food poisoning, stomachache, soaking ginger in boiling water and drinking tea. As a pharmacological action, gastric juice secretion, digestion enhancement, cardiac excitability, blood circulation promotion, fungal action have been reported.

These thistles, bellflowers, ducks, pears, coltsfoot, loofah, ginger and rice flakes have a weight ratio of 1: 1-3: 1-3: 1-3: 0.4-1: 0.4-1: 0.4-1: 0.4-1, preferably Preferably in a weight ratio of 1: 1-2: 1-2: 1-2: 0.5-0.8: 0.5-0.8: 0.5-0.8: 0.5-0.8.

When the content of bellflower, reddock, pear, coltsfoot, loofah, ginger and rice flakes based on thistle is less than the lower limit, the effect of improving, preventing or treating asthma and vascular disease may be lower than that of using each substance alone. If the upper limit is exceeded, the effect of improving, preventing or treating asthma and vascular diseases may be reduced.

When using thistle, bellflower, dorado, pear, coltsfoot, loofah, ginger, and rice snow alone, 1.5 to 20 times lower than thistle, bellflower, dorado, pear, coltsfoot, loofah, ginger and rice snow Show efficacy.

The form of the composition of the present invention may be prepared in the form of granules, pills, powder, juice, tea bags and the like.

For example, in the case of producing granules or pill, the milk thistle mixed extract is mixed with each powder of lyophilized powder and pulverized bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice flakes with water to prepare a dough. Using the prepared dough is molded in the form of granules or rings.

As another example, in the case of producing granules, powders, pills and juices, the milk thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow were mixed in the ratio of the present invention, and the extract of the bath-water extract at 80 to 100 ° C. was filtered. After lyophilization and powdering, the obtained powder may be molded to obtain granules or rings.

As another example, in the case of granules, powders, pears and blues, the milk thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow are mixed in the ratio of the present invention and extracted by boiling water at 80 to 100 ° C. for 20 to 30 hours. After mixing the extract and the powder thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice flakes in the ratio of the present invention in a weight ratio of 4-5: 1, and then the mixture at 60 to 70 ℃ 40 Blue water may be obtained by extracting and condensing the bath for from about 55 hours. In addition, the concentrated concentrate may be dried to obtain a powder. The concentrate may be dried to form a granule or a ring, and then dried again to obtain a complete granule or ring.

With this method, raw material powders are used, which eliminates the use of materials such as excipients and can yield higher amounts of active ingredients.

As another example, when the tea bag is manufactured, the powder obtained by lyophilizing the powder of the extract of the thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow is roasted at 80 to 120 ° C. in a tea bag.

The mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow of the present invention is broadly so that the mixture of thistle, bellflower, derad, pear, coltsfoot, loofah, ginger and rice snow can be administered to the animal. Mixed artifacts of formulated thistles, bellflowers, duckheads, pears, coltsfoot, loofah, ginger, and rice flakes are also meant to include mixed powders of thistles, bellflower, duckweeds, pears, coltsfoot, loofah, ginger, and riceeyes. Although the present invention was conducted with a mixture of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow, in the same form as the mixed artifact of thistle, bellflower, deodeok, pear, coltsfoot, scrubber, ginger and rice snow It will be apparent to those skilled in the art that the desired effect can also be achieved.

On the other hand, the term 'containing as an active ingredient' herein means containing an amount sufficient to achieve the efficacy or activity of the mixture of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice bran. In one example, the mixture of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice bran is used at a concentration of 10 to 1500 μg / ml, preferably 100 to 1000 μg / ml. Thistle, bellflower, reddock, pear, coltsfoot, scrubber, ginger and rice flakes are natural products and do not have adverse effects on the human body even when administered in large doses. Thistle, bellflower, reddock, pear, coltsfoot, scrubber, ginger and The upper limit of the quantity of the mixture of rice bran can be carried out by those skilled in the art selecting within an appropriate range.

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 adjuvant may include excipients, disintegrants, sweeteners, binders, coatings, swelling agents, lubricants, Lubricants, flavors and the like can be used.

The pharmaceutical composition may be preferably formulated into a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers in addition to the active ingredient described above for administration.

Formulation forms 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, nontoxic, 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 include, but are not limited to, natural and synthetic gums such as starch, gelatin, glucose or beta-lactose, corn sweeteners, acacia, trackercance 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 in compositions formulated in liquid solutions are sterile and biocompatible, which include saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, 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. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

Furthermore, the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be formulated according to each disease or component according to the appropriate method in the art.

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, or the like, and preferably, oral administration. .

Suitable dosages of the pharmaceutical compositions of the invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, condition of food, time of administration, route of administration, rate of excretion and response to reaction, Usually an experienced physician can easily determine and prescribe a dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10 g / kg.

The pharmaceutical compositions of the present invention may be prepared in unit dose form or formulated using pharmaceutically acceptable carriers and / or excipients or incorporated into multi-dose containers. 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 extracts, powders, granules, tablets or capsules, and may further include a dispersant or stabilizer.

In another aspect, the present invention provides a food composition for improving, preventing or treating asthma and vascular diseases, which contains a mixture of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice eyes as an active ingredient.

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

The food composition of the present invention may include, as an active ingredient, a mixture of thistle, bellflower, edodes, pears, coltsfoot, loofah, ginger, and rice bran, as well as ingredients commonly added in food production, for example, protein, Carbohydrates, fats, nutrients, seasonings and flavoring agents. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared with a drink and a beverage, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, in addition to the mixture of thistle, bellflower, reddock, pear, coltsfoot, loofah, ginger and rice snow of the present invention, Fruit juice, various plant extracts, and the like may be further included.

The present invention provides a health functional food comprising a food composition for improving, preventing or treating asthma and vascular diseases, which comprises a mixture of the thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice eyes as an active ingredient. Health functional food is a mixture of milk thistle, bellflower, reddock, pear, coltsfoot, loofah, ginger and rice snow to food materials such as beverages, teas, spices, gums, confectionery, etc. As a food, it means that when ingested to bring a specific effect on health, unlike general medicine has the advantage that there is no side effect that can occur when taking long-term use of the drug as a raw material. The health functional food of the present invention thus obtained is very useful because it can be consumed on a daily basis. The amount of the mixture of thistle, bellflower, reddock, pear, coltsfoot, loofah, ginger and rice bran in such a dietary supplement cannot be defined uniformly depending on the type of dietary supplement. What is necessary is just to add in the range which is not impaired, and it is the range of 0.01-50 weight% normally with respect to a target food, Preferably it is 0.1-20 weight%. In addition, in the case of a health functional food 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 dietary supplement of the present invention may be in the form of pills, tablets, capsules or beverages.

The present invention also provides the use of a mixture of thistles, bellflowers, tortillas, pears, coltsfoot, scrubbers, ginger and rice bran for the manufacture of a medicament or food for the improvement, prevention or treatment of asthma and vascular diseases. As described above, a mixture of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice bran can be used for the purpose of improving, preventing or treating asthma and vascular diseases.

The present invention also provides a method for ameliorating, preventing or treating asthma and vascular disease, comprising administering to a mammal an effective amount of a mixture of thistle, bellflower, tortilla, pear, coltsfoot, loofah, ginger and rice bran.

As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experimentation, preferably human.

As used herein, the term “effective amount” means the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, as thought by a researcher, veterinarian, doctor or other clinician, Amounts that induce alleviation of the symptoms of the disease or disorder. The effective amount and frequency of administration for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimum dosage to be administered can be readily determined by one skilled in the art and includes the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, general health of the patient. It may be adjusted according to various factors, including the condition, sex and diet, time of administration, route of administration and rate of composition, duration of treatment, and drugs used simultaneously. In the method for preventing, treating or improving the present invention, in adults, when a mixture of thistle, bellflower, reddock, pear, coltsfoot, loofah, ginger and rice bran is administered once to several times a day, 0.001 g / kg to 10 g Administration at a dose of / kg is preferred.

In the method of treatment of the present invention, the composition comprising a mixed extract of thistle, bellflower, tortilla, pear, coltsfoot, loofah, ginger and rice eye as active ingredients is oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal Administration may be in conventional manner via the transdermal, topical, intraocular or intradermal route.

Hereinafter, preferred examples are provided to help understanding of the present invention, but the following examples are merely for exemplifying the present invention, and various changes and modifications within the scope and spirit of the present invention are apparent to those skilled in the art. It is natural that such variations and modifications fall within the scope of the appended claims.

Example 1.Bangtang Extract

Milk thistle

1 part by weight of thistle flower, a mixture of stems and leaves (stem: leaf = 1: 2 weight ratio), 16.4 parts by weight, and 45 parts by weight of water, followed by extraction with a water bath at 95 ° C. for 24 hours to obtain an A extract, thistle root 0.3 Weight parts and 45 parts by weight of water extraction at room temperature for 24 hours at 95 ℃ to obtain a B extract and then lyophilized to prepare A powder and B powder, respectively, to prepare a mixed extract powder.

Bantang Extract

100 parts by weight of thistle, 100 parts by weight of bellflower, 100 parts by weight of pear, 100 parts by weight of pear, 60 parts by weight of butter, 60 parts by weight of loofah, 60 parts by weight of ginger and 60 parts by weight of rice, and then mixed at 90 ° C. for 24 hours. After stirring for a while, the compressed solution obtained by compressing the heated solution and the floating material was mixed, sterilized at 100 ° C. for 5 minutes, and then filtered to obtain a heated bath extract. At this time, no solvent was used other than the above materials.

Example 2. Extract of Tangtang + Powder-> Extract of Tangtang

In the same manner as in Example 1, 100 parts by weight of thistle, 100 parts by weight, bellflower 100 parts by weight, 100 parts by weight of pears, 60 parts by weight of butterbur, 60 parts by weight of loofah, 60 parts by weight of ginger and 60 g of rice snow After mixing the parts by weight and agitation at 90 ℃ for 24 hours; 100 mg by weight of thistle, 100 parts by weight, bellflower 100 parts by weight, 100 parts by weight of pear, 60 parts by weight of butter, 60 parts by weight of loofah, 60 parts by weight of ginger and 60 parts by weight of crushed rice powder; The mixture was mixed at a weight ratio of 4: 1, and then the mixture was extracted by boiling water at 60 ° C. for 48 hours to obtain an extract.

Example 3. Addition of thistle root roots

In the same manner as in Example 1, when preparing the thistle powder, the milk thistle roots were extracted with water, the remaining residues were dried and pulverized to obtain C powder (root residue powder), and then A powder, B powder and C powder were prepared. Thistle mixed powder (0.3 parts by weight of C powder with respect to 100 parts by weight of A powder + B powder) to prepare a thistle mixed extract powder and then using this to obtain a bath extract.

Example 4 Kneading

In the same manner as in Example 1, but instead of preparing a water extract, thistle 100 parts by weight, bellflower 100 parts by weight, deodeok 100 parts by weight, pear 100 parts by weight, butterbur 60 parts by weight, scrubber 60 parts by weight, ginger 60 parts by weight and 60 parts by weight of rice flakes were mixed and pulverized.

Comparative Example 1. Thistle omitted

The same procedure as in Example 1, except that thistle was omitted to obtain a water extract.

Comparative Example 2. Omitted Rice Eye

The same procedure as in Example 1 was carried out, but the rice extract was obtained by omitting rice eyes.

Comparative Example 3. Using Rice Bran

In the same manner as in Example 1, but using a rice bran instead of rice eyes to obtain a bath extract.

<Test Example>

Test Example 1. Measurement of Cell Viability

10 ul of HUVECs (human vascular endothelial cells, American Type Culture Collection (Manassas, VA, USA)) were used to induce neovascularization, and the powders of Examples and Comparative Examples were treated in a concentration-dependent manner. Apoptosis trends were determined by WST-1 assay.

division No treatment 0.3 uM 3 uM 30 uM Example 1 98.3 98.0 98.1 97.9 Example 2 99.0 98.5 98.2 98.0 Example 3 98.2 98.1 98.2 98.0 Example 4 98.1 98.2 98.0 97.7 Comparative Example 1 98.1 98.0 98.1 97.2 Comparative Example 2 98.2 98.1 97.7 97.8 Comparative Example 3 98.3 98.1 98.0 97.6

As shown in Table 1, the extracts prepared according to Examples 1 to 4 and the extracts prepared according to Comparative Examples 1 to 3 of the present invention was confirmed that the cytotoxicity is low because the cell viability is excellent.

Test Example 2 Evaluation of Cell-Based Efficacy Using Asthma_FACS

The binding between TSLP and TSLP receptors activates various signal transduction pathways, mainly utilizing the JAK / STAT pathway. TSLP signaling is also well known for the characteristic phosphorylation of STAT5 in STAT molecules. Therefore, in order to confirm whether the compounds according to the present invention effectively inhibit the binding between TSLP and TSLP receptor, it is possible to check the phosphorylation degree of the STAT5 molecule in the JAK / STAT pathway activated by such binding. If the compounds according to the present invention effectively inhibit the binding between TSLP and TSLP receptor, the phosphorylation level of STAT5 molecule may be inhibited.

In order to confirm this fact, the following experiment was carried out: HMC-1, a human mast cell line, was cultured to maintain an appropriate amount of cells in a 96-well plate. The supernatant was removed and TSLP (100 ng / mL) and peptides at appropriate concentrations (0.3, 3, 30 μM) were mixed and treated for 30 minutes on the cells, and the cells were then fixed with a cytofix. Subsequently, the cells were permeabilized with a permeabilization buffer, followed by intracellular staining with anti-pSTAT5 antibody at 4 ° C. for 30 minutes. Cells were washed three times with the same buffer and analyzed by flow cytometry.

Table 2 below shows the phosphorylation of intracellular STAT5 molecules compared to the control group when the extracts of Examples and Comparative Examples were added at concentrations of 0.3, 3 and 30 μM, respectively. The control group was treated only with the cytokine TSLP, and phosphorylation of intracellular STAT5 molecules was 100%.

division Phosphorylation level of intracellular STAT5 molecules (%) 0.3 uM 3 uM 30 uM Example 1 73.8 70.1 66.8 Example 2 71.4 64.5 63.0 Example 3 72.0 66.8 64.1 Example 4 80.1 76.4 73.8 Comparative Example 1 87.2 83.6 77.2 Comparative Example 2 88.1 84.2 78.6 Comparative Example 3 98.2 94.0 89.9

As shown in Table 2, the extract prepared according to Examples 1 to 4 of the present invention is effective to bind the cytokine TSLP and TSLP receptors, which play a key role in causing asthma disease, as compared to Comparative Examples 1 to 3 By inhibiting TSLP-mediated signal transduction, thereby enabling fundamental prevention and treatment of asthma diseases.

In particular, it was confirmed in Examples 1 to 4 that Examples 2 and 3 more effectively inhibit the binding between TSLP and TSLP receptor than Examples 1 and 4.

Test Example 3 Evaluation of Inhibitory Effect on Vascular Disease_Monocyte Adhesion

It was confirmed that the extracts prepared in Examples and Comparative Examples inhibit the adhesion of monocytes involved in the initial atherosclerosis in vascular endothelial cells. To this end, HUVEC cells were dispensed at ⁵ × 10 ^{4 per} well (number of cells) in a 48 well plate, and the cells were attached to the plate, and each of the extracts prepared in Examples and Comparative Examples was treated for 12 hours. Thereafter, TNF-α 10 ng / ml was treated with HUVEC for 12 hours, and monocytes (U937 cells) labeled with Calcein green were attached to 48-well plates with HUVEC and co-cultured for 1 hour. After co-culture, the cell culture solution was removed, the cells were washed twice with PBS (phosphated buffered saline solution), treated with 1% paraformaldehyde, and the cells were fixed. The degree of adhesion was confirmed, and the results are shown in the following [Table 3]. The adhesion of monocytes in the TNF-a treated group was 125%.

division Monocyte adhesion degree (%) 0.3 uM 3 uM 30 uM Example 1 77.4 43.6 25.1 Example 2 55.1 25.4 13.4 Example 3 60.5 33.8 20.4 Example 4 80.6 50.4 30.8 Comparative Example 1 98.2 88.0 77.1 Comparative Example 2 114.8 96.7 80.4 Comparative Example 3 120.0 111.2 90.6

As shown in Table 3, the extract prepared according to Examples 1 to 4 of the present invention was confirmed to significantly reduce the adhesion of monocytes in a concentration-dependent manner compared to Comparative Examples 1 to 3. Therefore, the extract prepared according to Examples 1 to 4 is expected to have an excellent effect of inhibiting vascular diseases such as atherosclerosis by inhibiting adhesion of monocyte cells in vascular endothelial cells.

In particular, it was confirmed in Examples 1 to 4 that Examples 2 and 3 further inhibit the adhesion of monocyte cells as compared with Examples 1 and 4.

Test Example 3 Evaluation of Inhibitory Effect on Vascular Disease_ICAM-1 and VCAM-1 Expression

Luciferase promoter assay (luciferase promoter assay) confirmed that the extracts prepared according to the Examples and Comparative Examples inhibit the expression of ICAM-1 and VCAM-1 proteins in vascular endothelial cells.

Promoter activity of ICAM-1 and VCAM-1 was confirmed through a luciferase assay using a luciferase assay system kit (Promega). To this end, HUVEC cells were dispensed at ⁵ × 10 ⁴ / well into 48 well plates to attach the cells to the plates, and then 1 μg of ICAM-1 or VCAM-1 promoter-luciferase (VCAM-1 promoter-luciferase) to HUVEC cells. ), 0.2 μg of pCMV-β-galactosidase was transformed with Lipofectamine ™ 2000 (Lipofectamine ™ 2000). After 4 hours, the cell culture was replaced with medium without FBS, and the extracts prepared according to Examples and Comparative Examples were pretreated with HUVEC for 12 hours, followed by TNF-α 5 ng / ml for 12 hours. The cells were then centrifuged at 14,240 μg for 10 minutes after lysis, and then the luciferase and β-galactosidase activities of the supernatants were measured. β-galactosidase assays were identified using 250 μl assay buffer (0.12 M Na2HPO4, 0.08 M NaH2PO4, 0.02 M KCl, 0.002 M MgCl2, 0.1 M β-mercaptoethanol, 50 μg onitrophenyl-β-galactoside) It was. Luciferase activity was leveled by the activity of β-galactosidase, and the results are shown in [Table 4].

division ICAM-1 expression inhibitory activity 0.3 uM 3 uM 30 uM Example 1 418.2 ± 50.16 249.7 ± 43.18 150.44 ± 40.67 Example 2 301.6 ± 22.48 149.5 ± 19.47 101.56 ± 23.48 Example 3 350.5 ± 31.80 206.8 ± 23.48 128.45 ± 30.41 Example 4 427.8 ± 22.71 291.5 ± 38.69 180.67 ± 33.18 Comparative Example 1 429.2 ± 53.70 324.5 ± 18.47 254.39 ± 43.60 Comparative Example 2 418.1 ± 18.47 329.7 ± 49.61 265.17 ± 21.48 Comparative Example 3 426.9 ± 36.91 385.4 ± 55.43 320.48 ± 25.11

division VCAM-1 expression inhibitory activity 0.3 uM 3 uM 30 uM Example 1 171.5 ± 10.15 130.5 ± 11.43 118.2 ± 12.38 Example 2 140.18 ± 5.61 109.48 ± 9.62 93.4 ± 8.25 Example 3 153.4 ± 9.85 122.1 ± 8.44 102.4 ± 9.68 Example 4 178.8 ± 8.69 139.7 ± 9.44 128.7 ± 10.46 Comparative Example 1 188.2 ± 11.38 165.4 ± 13.47 141.2 ± 8.13 Comparative Example 2 185.6 ± 9.69 166.1 ± 10.43 144.8 ± 11.42 Comparative Example 3 194.5 ± 14.18 177.9 ± 11.75 161.4 ± 9.68

As shown in Tables 4 and 5 above, the increased activity of ICAM-1 and VCAM-1 due to TNF-α treatment decreased in a concentration dependent manner as treated with extracts prepared according to Examples 1-4 of the present invention. We confirmed that we were doing.

Moreover, the extract prepared according to Examples 1 to 4 of the present invention was confirmed that the expression inhibitory activity of ICAM-1 and VCAM-1 is superior to Comparative Examples 1 to 3, Example 2 and in Examples 1 to 4 It was confirmed that 3 is superior to Examples 1 and 4.

Hereinafter, the preparation examples of the composition containing the powder of the present invention will be described, but the present invention is not intended to limit the present invention, but merely to explain in detail.

Formulation Example 1 Preparation of Powder

500 mg of extract powder obtained in Example 1

Lactose 100 mg

Talc 10 mg

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

Formulation Example 2 Preparation of Tablet

300 mg of extract powder obtained in Example 1

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation Example 3 Preparation of Capsule

200 mg of extract powder obtained in Example 1

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

600 mg of extract powder obtained in Example 1

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO _4, 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule.

Formulation Example 5 Preparation of Liquid

4 g of extract powder obtained in Example 1

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added to the purified water to dissolve, the lemon flavor is added appropriately, the above components are mixed, and then purified water is added to adjust the total amount to 100 g. To prepare a liquid formulation.

Formulation Example 6 Preparation of Granules

1,000 mg of extract powder obtained in Example 1

Vitamin Mixture

70 μg of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinamide 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5 mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

15 mg potassium monophosphate

Dicalcium Phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for granules in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above components are mixed according to a conventional granulation method, and then granulated. It can be prepared and used in the manufacture of health functional food composition according to a conventional method.

Formulation Example 7 Preparation of Functional Beverage

 1,000 mg of extract powder obtained in Example 1

Citric Acid 1,000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 mL of purified water

After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilized and then refrigerated Used to prepare functional beverage compositions of the invention.

Although the composition ratio is mixed with a relatively suitable component for a preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (8)

Pharmaceutical composition for the prevention or treatment of asthma and vascular diseases, comprising a mixture consisting of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice eyes as an active ingredient. The method of claim 1, wherein the thistle, bellflower, reddock, pear, coltsfoot, loofah, ginger and rice bran is 1: 1-3: 1-3: 1-3: 0.4-1: 0.4-1: 0.4-1: 0.4 The pharmaceutical composition for the prevention or treatment of asthma and vascular diseases, characterized in that the extract by mixing in a weight ratio of -1 and extracted by boiling water at 80 to 100 ℃. The pharmaceutical composition for preventing or treating asthma and vascular diseases according to claim 1, wherein the vascular disease is a disease selected from the group consisting of peripheral vascular obstruction, vascular restenosis, angina pectoris, myocardial infarction and ischemic heart disease. The method of claim 1, wherein the thistle is a mixed extract of a flower, a stem and a leaf, and a root of the milk thistle mixed at a weight ratio of 1: 14-25: 0.1-0.9. Therapeutic pharmaceutical composition. The pharmaceutical composition for preventing or treating asthma and vascular diseases according to claim 4, wherein the mixture of stems and leaves is mixed at a weight ratio of 1: 1-4. The method of claim 4, wherein the mixed extract is a mixture of the thistle flower, the mixture of the stem and the leaves of the extract extracted in a bath at 80 to 100 ℃, and the root extract at 80 to 100 ℃, characterized in that the mixture of the extract Pharmaceutical composition for the prevention or treatment of asthma and vascular diseases. The pharmaceutical composition for preventing or treating asthma and vascular diseases according to claim 6, wherein a powder obtained by drying and pulverizing the residue remaining after extracting the roots at 80 to 100 ° C. in a mixed extract is added to the mixed extract. Food composition for the prevention or improvement of asthma and vascular diseases, characterized in that it contains a mixture of thistle, bellflower, deodeok, pear, coltsfoot, loofah, ginger and rice snow as an active ingredient.