KR102541649B1 - A composition for improving, preventing and treating of woman menopause related disease - Google Patents

Abstract

The present invention relates to a composition for preventing, treating or improving female menopausal symptoms, comprising a milk thistle extract; And a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, sage, and ginger; by containing as an active ingredient, various symptoms caused by estrogen deficiency in menopausal women can be improved, and since it is not toxic, it is in the form of food. can be consumed as

Description

A composition for preventing, treating, or improving female menopausal symptoms including thistle, hyssop, kudzu, aronia, pomegranate, hasuo and ginger {A composition for improving, preventing and treating of woman menopause related disease}

The present invention relates to a composition for preventing, treating, or improving female menopausal symptoms containing a mixture including thistle, hyssop, kudzu, aronia, pomegranate, hawthorn, and ginger as an active ingredient.

In living in the industrialized modern age with the development of science and civilization, human lifespan is gradually extended, and at the same time, immunity is lowered and aging is progressed due to various stresses, pollution, and natural aging phenomena. In particular, women suffer from physical and mental difficulties due to menopausal symptoms that begin gradually after the age of 40.

Menopause is a type of endocrine syndrome, and refers to a transitional period in which physiological and sexual functions are reduced or lost due to a decrease in female hormones, that is, estrogen, caused by overall and gradual aging of ovarian function. These menopausal symptoms include symptoms due to vascular changes such as hot flashes, tachycardia, sweating or headaches, symptoms due to musculoskeletal changes such as muscle pain, joint pain and back pain, and symptoms due to genitourinary changes such as frequent urination or urinary incontinence. There are symptoms caused by changes in the brain nervous system such as memory loss, depression, loss of concentration, and dizziness. In addition, symptoms such as vision loss and skin and hair changes occur, and women such as osteoporosis or cardiovascular disease due to hormonal changes diseases that can be fatal to your health.

Therefore, in order to improve the physical and mental health and quality of life of middle-aged women, the development of therapeutic agents capable of improving menopausal symptoms has been required, and drugs such as hormone replacement therapy and non-steroidal agents have been developed to improve these menopausal symptoms. has been However, most of these drugs are known to have side effects such as headaches and weight gain. In particular, even in the case of estrogen replacement therapy, since hormones are artificially administered into the body, they are rejected along with uterine bleeding, stroke, and heart disease. It is known that it may increase the risk of developing seizures, breast and uterine cancer.

Therefore, because of these problems, interest in replacing estrogen therapy with natural methods ingested in the form of food or additives is increasing, and the development of new menopausal symptom treatments that have excellent effects in relieving menopausal symptoms without side effects is required. It is becoming.

On the other hand, estrogen has various biological functions including cell number increase and differentiation. Biological actions of estrogen exert their activity through two estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) belonging to the nuclear receptor superfamily. The mechanism of action of the estrogen receptor is the combination of estrogen and intracellular estrogen receptors to form a dimer of the receptors, which are located in the promoters of the target gene. Specific estrogen response elements (EREs) ) to regulate the expression of target genes. Since the two estrogen receptors have different tissue distribution patterns and ligand binding capacity, these differences allow for different selective roles of estrogen receptor agonists and antagonists in different tissues. In addition, substances acting on estrogen receptors are being used as targets for hormone replacement therapy for postmenopausal women and chemotherapy for genital cancer.

Therefore, if a natural product that activates the estrogen receptor is discovered from a natural product that has no side effects on the human body, it can be usefully used for preventing, treating, or improving female menopausal symptoms.

Republic of Korea Patent Publication No. 0129811 Republic of Korea Patent No. 10-2042486

An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of female menopausal symptoms containing a mixture containing thistle, hyssop, kudzu, aronia, pomegranate, hawthorn and ginger as an active ingredient.

In addition, another object of the present invention is to provide a food composition for preventing or improving female menopausal symptoms containing a mixture containing thistle, hyssop, kudzu, aronia, pomegranate, sewage and ginger as an active ingredient.

The pharmaceutical composition for preventing or treating female menopausal symptoms of the present invention for achieving the above object is a milk thistle extract; And a mixed extract obtained by extracting a mixture consisting of usul, kudzu, aronia, pomegranate, hawthorn and ginger; may contain as an active ingredient.

With respect to 100 parts by weight of the thistle extract, 5 to 30 parts by weight of hydrangeas, 100 to 150 parts by weight of kudzu, 5 to 30 parts by weight of aronia, 5 to 30 parts by weight of pomegranate, 5 to 30 parts by weight of sewage, and 1 to 20 parts by weight of ginger can be mixed.

The thistle may be a mixture of flowers, stems and leaves of thistles, and roots mixed in a weight ratio of 1: 14-25: 0.1-0.9.

The female menopausal symptoms include hot flashes, sweating, dry skin, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, dysuria, urgency, concentration disorder, short-term memory disorder, anxiety, nervousness, memory loss, muscle pain, arthralgia, and It may be one or more selected from the group consisting of osteoporosis.

In addition, the food composition for preventing or improving female menopausal symptoms of the present invention for achieving the above other object is thistle extract; And a mixed extract obtained by extracting a mixture consisting of usul, kudzu, aronia, pomegranate, hawthorn and ginger; may contain as an active ingredient.

The thistle extract of the present invention; and a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, hasuo, and ginger; the mixture has estrogenic activity in cells and acts as an estrogen receptor agonist, so it is effective in menopausal women due to estrogen deficiency. It can be usefully used as a hormone replacement therapy that can improve various symptoms. In addition, since it is non-toxic, it can be ingested in the form of food.

The present invention relates to a composition for preventing, treating, or improving female menopausal symptoms containing a mixture including thistle, hyssop, kudzu, aronia, pomegranate, hawthorn, and ginger as an active ingredient.

Hereinafter, the present invention will be described in detail.

The composition for preventing, treating or improving female menopausal symptoms of the present invention includes a milk thistle extract; And a mixed extract obtained by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, hawthorn and ginger; contains as an active ingredient. In addition, stevia may be added in addition to the above ingredients.

thistle

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

The white-patterned thistle (Silybum marianum (L.) Gaertn.) is a plant of deep, shiny green with milky white leaf veins, and is a thin and long plant divided into root-leaves with wavy patterns and thorns at the edges. It is mainly found in embankment fences and abandoned land. The useful parts of the plant are the whole herb, root, leaves, seeds, and hull. Milk thistle seeds contain a flavonoid compound known as silymarin. Thistle seed extract contains 70-80% silymarin.

The thistle according to the present invention is a mixed extract of a mixture of flowers, stems and leaves, and roots of thistle.

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

In addition, the stems and leaves of thistles are mixed in a weight ratio of 1:1-4, preferably 1:2-3. If the content of the leaf on the basis of the stem is less than the lower limit, the bitter taste may be strong, and if the content exceeds the upper limit, it is not preferable for preventing, treating, or improving female menopausal symptoms.

In addition, since the thistle root is harvested once every three years, unlike flowers, stems and leaves that are harvested twice a year, it is preferable to use it after drying.

The mixture of flowers, stems and leaves, and roots of thistle are mixed in a weight ratio of 1:14-25:0.1-0.9, preferably 1:16-19:0.4-0.8. If the content of the mixture of stems, leaves, and roots on a flower basis is less than the lower limit above, the effect on preventing, treating, or improving female menopausal symptoms may not be excellent, and if it exceeds the upper limit above, the bitter taste is strong and female menopausal The effectiveness of preventing, treating or ameliorating symptoms may be reduced.

The mixed extract of the present invention is a water bath extract extracted at 80 to 100° C. for 20 to 30 hours, preferably 24 to 28 hours. If the extraction temperature and time are less than the lower limit, the active ingredient may not be extracted, and if it exceeds 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, the effect of preventing, treating, or improving female menopausal symptoms is insignificant and a bitter taste may be strongly generated.

Specifically, the mixed extract is extracted by mixing a mixture of flowers, stems and leaves with hot water, and separately extracting the roots with hot water and then mixing them. Unlike the present invention, when all of the flowers, a mixture of stems and leaves, and roots are mixed and extracted in hot water, the bitter taste is strong and the effect of preventing, treating, or improving female menopausal symptoms may be reduced.

The method for preparing this mixed extract of thistle includes (a) mixing a mixture of flowers, stems and leaves of thistle and extracting in hot water at 80 to 100 ° C. to obtain an extract; (b) obtaining an extract by extracting the roots of thistle in hot water at 80 to 100 ° C; And (c) freeze-drying the extracts obtained in steps (a) and (b), respectively, and pulverizing and mixing them. In addition, after step (c), (d) drying and pulverizing the residue remaining after extraction in step (b); and (e) mixing 100 parts by weight of the powder mixed in step (c) with 0.1 to 3 parts by weight of the powder in step (d).

Unlike the above steps (a) and (b), when the flowers, the mixture of stems and leaves, and the roots are all mixed and extracted in hot water, the bitter taste is strong and the effect of preventing, treating, or improving female menopausal symptoms is reduced. can; The yield may be lowered when the flowers, the mixture of stems and leaves, and the roots are all separately extracted in hot water.

In the case of adding the root residue powder prepared in step (D), the effect on diseases can be significantly improved compared to the case where the root residue powder is not added.

Wooseul

When the raw material is used, it removes blood and boils, and when steamed, it strengthens the muscles and bones by looking at the liver and kidneys. It is used for menstrual irregularities and postpartum abdominal pain by removing blood, and treats rashes in the mouth and tongue caused by Yinheohwadong. As for the pharmacological action, uterine stimulation, cholesterol lowering, diuretic, blood sugar lowering, and liver function improvement have been reported.

This hyssop is mixed in 5 to 30 parts by weight, preferably 10 to 20 parts by weight, based on 100 parts by weight of the thistle extract. If the content of wooseul is less than the lower limit above, the effect of improving, preventing or treating female menopausal symptoms may be lower than when each substance is used alone, and if it exceeds the upper limit above, the improvement, prevention or treatment of female menopausal symptoms effect may be diminished.

arrowroot

The kudzu is a perennial plant that does not freeze and die in winter and most of the stems survive.

The arrowroot is mixed in an amount of 100 to 150 parts by weight, preferably 120 to 130 parts by weight, based on 100 parts by weight of the thistle extract. If the content of kudzu is less than the lower limit, the desired effect may not be improved, and if the content is greater than the upper limit, the functionality may be reduced and the desired effect may be reduced.

aronia

When used alone, the aronia has little effect on the prevention, treatment, or improvement of female menopausal symptoms, but when used in combination with the thistle extract, hyssop, and kudzu, compared to the case when aronia is used alone, the efficacy is 1.5 to 20 times superior see.

The aronia is mixed in 5 to 30 parts by weight, preferably 10 to 20 parts by weight, based on 100 parts by weight of thistle extract. If the content of aronia is less than the lower limit, there may be no effect of preventing, treating, or improving female menopausal symptoms, and if it exceeds the upper limit, the sensory properties may decrease.

Pomegranate

Both the fruit and peel of the pomegranate are good for preventing high blood pressure and arteriosclerosis, and are effective for women's diseases and boils. In particular, it has excellent medicinal effects when dysentery occurs and contains volatile alkaloids, so it is used as a parasite, especially a tapeworm remedy.

Such pomegranate is mixed in 5 to 30 parts by weight, preferably 10 to 20 parts by weight, based on 100 parts by weight of thistle extract. If the content of aronia is less than the lower limit, there may be no effect of preventing, treating, or improving female menopausal symptoms, and if it exceeds the upper limit, the effect may be rather reduced.

In addition, compared to when pomegranate is used alone, the effect of preventing, treating, or improving female menopausal symptoms is further improved when used together with thistle extract, hyssop, and aronia. In particular, pomegranate, hyusul and aronia show 1.5 to 10 times higher efficacy than when used in the same content.

Ha Suo

The sewage is a special plant that grows only in Korea, and has the efficacy of interpolation, Iksin, yanghyeol, and wind as a gangjeong, tonic or laxative. It treats liver, kidney disease, whitening of hair, anemia due to hyeonun, yosei weakness, musculoskeletal pain, oil well, uterine bleeding, bandage, chronic ailment, chronic hari, chronic hepatitis, carbuncle, spleen, intestinal wind, and hemorrhoids.

When such sewage is used together with thistle extract, ginger, and pomegranate, more excellent efficacy occurs in terms of female menopausal symptoms than when each of the above substances is used.

The sewage is mixed in 5 to 30 parts by weight, preferably 10 to 15 parts by weight, based on 100 parts by weight of the thistle extract. If the content of sewage is less than the lower limit, there may be no effect of preventing, treating, or improving female menopausal symptoms, and if it exceeds the upper limit, the sensory function may be reduced and toxicity may occur.

ginger

The ginger is native to Southeast Asia and is grown as a vegetable. In oriental medicine, dried rhizomes are used as medicinal materials. Ginger treats chills caused by colds, fever, headaches, vomiting, seawater, and phlegm, and is also effective for stomach pain and diarrhea caused by food poisoning. . As pharmacological action, it has been reported that it promotes secretion of gastric juice, enhances digestive power, stimulates the heart, promotes blood circulation, and inhibits bacteria.

When such ginger is used in combination with thistle extract, hyssop, and aronia, more excellent efficacy occurs in terms of female menopausal symptoms than when each of the above substances is used.

The ginger is mixed in 1 to 20 parts by weight, preferably 1 to 5 parts by weight, based on 100 parts by weight of the thistle extract. If the content of ginger is less than the lower limit, there may be no effect of preventing, treating, or improving female menopausal symptoms, and if it exceeds the upper limit, the sensory function may be reduced and toxicity may occur.

Stevia

The stevia ( Stevia rebaudiana ) grows around rivers or wetlands, and has been using stevia leaves as a sweetener since ancient times, but recently, as the harmfulness of saccharin, a synthetic sweetener, has become a problem, it has attracted attention again. Leaves contain stevioside, a sweetener, at 6-7% of the weight, and the content varies greatly depending on the individual. Its sweetness component is 300 times that of sugar, and it is used to make tea or substitute for gum and as a sweetener in soft drinks.

In the present invention, the use of stevia not only increases the sensibility, but also is effective in preventing, treating, or improving female menopausal symptoms when used together with thistle extract.

The stevia is mixed in an amount of 0.1 to 5 parts by weight, preferably 0.5 to 1 part by weight, based on 100 parts by weight of the thistle extract.

If the content of stevia is less than the lower limit, the effect of preventing, treating, or improving female menopausal symptoms may not be improved, and if the content exceeds the upper limit, the sensory properties may decrease.

In addition, the method for preparing a composition for preventing, treating or improving female menopausal symptoms of the present invention includes the steps of (A) obtaining a thistle extract by extracting a thistle extract; (B) obtaining a mixed extract by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, hasuo and ginger; (C) mixing and mixing the thistle extract, the mixed extract, and stevia;

First, in step (A), a mixture of thistle and dandelion is extracted with an extraction solvent to obtain a mixed extract.

Mixing conditions, extraction solvents and extraction conditions of the mixture are the same as those mentioned above.

Next, in the step (B), a mixture of wooseul, kudzu, aronia, pomegranate, sewage and ginger and an extraction solvent are mixed in a weight ratio of 1: 1 to 100, preferably 1: 5 to 20, and heated to 80 to 100 ° C. Extracted for 40 to 50 hours to prepare an extract. When the weight ratio of the mixture and the extraction solvent is out of the above range, a small amount of the active ingredients of the mixture of hyusul, kudzu, aronia, pomegranate, sewage and ginger may be extracted in the extract.

The extraction solvent for extracting the extract is water, lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. The extraction solvent is not particularly limited, but extracts extracted with water show excellent effects.

Next, in the step (C), stevia is added to and mixed with the mixture of the thistle extract and the mixed extract at room temperature.

The stevia is added after the thistle extract and the mixed extract are sufficiently mixed, but when the thistle extract and the mixed extract and stevia are added together, the functionality may be significantly reduced.

The composition of the present invention may be prepared in the form of gel, puree, juice, pill, substitute pill and granule.

For example, when prepared in the form of a gel or puree, the thistle extract prepared in step (A) and the mixed extract of hyssop, kudzu, aronia, pomegranate, sage and ginger prepared in step (B) and thistle extract After concentrating the mixture in a concentrator to a volume of 1/3 to 1/5 of the volume of the mixture, the step (C) is performed using the concentrate. That is, after mixing the concentrate and stevia, agar is added and stirred, and then sterilized to prepare a gel and puree.

As another example, when prepared in the form of juice, the mixture prepared in step (C) is sterilized and used.

As another example, when prepared in the form of pills, large pills and granules, the thistle extract prepared in step (A) and the mixed extract of wooseul, kudzu, aronia, pomegranate, sewage and ginger prepared in step (B) and thistle extract were concentrated with a concentrator to a volume of 1/5 to 1/7 of the volume of the mixture, and then stevia was added to the concentrate, aged in a water bath at 60 to 70 ° C for 40 to 50 hours, and then dried. and molded to produce pills, substitute pills and granules.

The thistle extract of the present invention; And a mixed extract obtained by extracting a mixture consisting of hyssop, kudzu, aronia, pomegranate, hasuo and ginger; a thistle extract in a broad sense; and a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, sage, and ginger; a mixed processed product formulated to be administered to animals, such as a thistle extract; And a mixed extract obtained by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, hasuo, and ginger. Although thistle extract in the present invention; And a mixed extract obtained by extracting a mixture consisting of hyssop, kudzu, aronia, pomegranate, hawthorn and ginger; although the experiment was conducted with a mixture consisting of thistle extract; And it will be expected by those skilled in the art that the desired effect can be achieved even in the form of a mixed processed product;

On the other hand, in the present specification, the term 'containing as an active ingredient' means thistle extract; And a mixed extract obtained by extracting a mixture consisting of hawthorn, kudzu, aronia, pomegranate, hawthorn and ginger; it means containing an amount sufficient to achieve the efficacy or activity of the mixture consisting of. For example, the thistle extract; and a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, rhubarb, and ginger; the mixture consisting of is used at a concentration of 10 to 1500 μg/ml, preferably 100 to 1000 μg/ml. milk thistle extract; And a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, hawthorn and ginger; a thistle extract included in the composition of the present invention because it has no side effects on the human body even when administered in excess as a natural product; And a mixed extract obtained by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, hawthorn and ginger; the quantitative upper limit of can be selected and carried out by those skilled in the art within an appropriate range.

The pharmaceutical composition of the present invention may be prepared using pharmaceutically suitable and physiologically acceptable adjuvants in addition to the above active ingredients, and the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, A lubricant or flavoring agent may be used.

The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.

Formulations 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 include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth 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.

In compositions formulated as liquid solutions, acceptable pharmaceutical carriers are sterile 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 if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare formulations for injections such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets.

Furthermore, using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field, it can be preferably formulated according to each disease or component.

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

The suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, sex, medical condition, food, administration time, route of administration, excretion rate and reaction sensitivity, A ordinarily skilled physician can readily determine and prescribe dosages 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 composition of the present invention is prepared in unit dosage form by formulation using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily performed by those skilled in the art. or it may be prepared by incorporating 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 contain a dispersing agent or stabilizer.

In addition, the present invention is a thistle extract; It provides a food composition for preventing, treating, or improving female menopausal symptoms containing a mixture consisting of as an active ingredient;

The food composition according to the present invention can be formulated in the same way as the pharmaceutical composition and 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, chocolate, pizza, ramen, other noodles, chewing gum, ice cream, vitamin complexes, and health supplements. etc.

The food composition of the present invention contains milk thistle extract as an active ingredient; And a mixed extract obtained by extracting a mixture consisting of arrowroot, kudzu, aronia, pomegranate, hasuo, and ginger; as well as may include ingredients commonly added during food manufacturing, such as proteins, carbohydrates, fats, and 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 such as conventional sugars such as dextrins and cyclodextrins and sugar alcohols such as xylitol, sorbitol and erythritol. As flavoring agents, natural flavoring agents [thaumatin, stevia extract (eg, 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 made into drinks and beverages, the milk thistle extract of the present invention; And a mixed extract obtained by extracting a mixture consisting of usul, kudzu, aronia, pomegranate, hasuo, and ginger; In addition, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be further included.

The present invention is the thistle extract; It provides a health functional food containing a food composition for preventing, treating or improving women's menopausal symptoms containing as an active ingredient; With health functional food, milk thistle extract; and mixed extract obtained by extracting a mixture consisting of arrowroot, kudzu, aronia, pomegranate, sage, and ginger; added to food materials such as beverages, teas, spices, chewing gum, confectionery, etc., or manufactured into encapsulated, powdered, and suspension products. This means that when ingested, it brings about a specific effect on health, but unlike general medicines, it has the advantage of not having side effects that may occur when taking medicines for a long period of time using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be consumed on a daily basis. Thistle extract in such a health functional food; And a mixed extract obtained by extracting a mixture consisting of arrowroot, kudzu, aronia, pomegranate, sage, and ginger; the amount of added is not uniformly regulated depending on the type of target health functional food, but the range that does not impair the original taste of the food It is added in, and is usually in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight, relative to the target food. 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 of the present invention may be in the form of pills, tablets, capsules or beverages.

In addition, the present invention relates to a milk thistle extract for the preparation of a medicine or food for preventing, treating or improving female menopausal symptoms; And a mixed extract obtained by extracting a mixture consisting of usul, kudzu, aronia, pomegranate, hasuo and ginger. extract of thistle as described above; And a mixed extract obtained by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, hawthorn and ginger; can be used for female menopausal symptoms.

In addition, the present invention provides an effective amount of thistle extract for mammals; It provides a method for improving, preventing or treating female menopausal symptoms comprising administering a mixture of; and a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, rhubarb, and ginger.

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

As used herein, the term "effective amount" means an amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, which is considered by a researcher, veterinarian, physician or other clinician, which is An amount that induces relief of the symptoms of a disease or disorder is included. It is obvious to those skilled in the art that the effective amount and frequency of administration of the active ingredient of the present invention will vary depending on the desired effect. Therefore, the optimal dose 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 the active ingredient and other ingredients contained in the composition, the type of formulation, and the patient's age, weight, and general health Condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, can be adjusted according to various factors including drugs used simultaneously. In the prevention, treatment or improvement method of the present invention, in the case of adults, thistle extract; And a mixed extract obtained by extracting a mixture consisting of arrowroot, kudzu, aronia, pomegranate, rhubarb, and ginger; it is preferable to administer the mixture at a dose of 0.001 g/kg to 10 g/kg when administered once or several times a day. do.

Thistle extract in the treatment method of the present invention; And a mixed extract obtained by extracting a mixture consisting of oxtail, kudzu, aronia, pomegranate, sage, and ginger; a composition comprising a mixture consisting of as an active ingredient can be used for oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal , can be administered in a conventional manner via transdermal, topical, intraocular or intradermal routes.

Hereinafter, preferred embodiments are presented to aid understanding of the present invention, but the following examples are merely illustrative of the present invention, and various changes and modifications are possible within the scope and spirit of the present invention. It is obvious to those skilled in the art, It goes without saying that these variations and modifications fall within the scope of the appended claims.

Example 1.

Preparation of milk thistle extract

1 part by weight of thistle flower, 18.6 parts by weight of a mixture of stems and leaves (stem:leaf = 1:2 weight ratio) and 45 parts by weight of water were mixed and extracted in hot water at 95 ° C for 24 hours to obtain A extract, followed by 0.4 parts by weight of thistle root parts by weight and 45 parts by weight of water were extracted with hot water at 95 ° C. for 24 hours to obtain B extract, and then lyophilized to prepare A powder and B powder, respectively, and mixed to prepare mixed extract powder of thistle.

preparation of mixtures

A mixture of 14 parts by weight of usul, 128 parts by weight of kudzu, 14 parts by weight of aronia, 14 parts by weight of pomegranate, 11 parts by weight of Hasuo, and 1 part by weight of ginger (the above content is based on 100 parts by weight of thistle extract) and water 1: A mixed extract was prepared by mixing at a weight ratio of 9 and extracting at 90 ° C. for 48 hours.

After mixing the thistle extract and the mixed extract, 0.8 parts by weight of stevia was added and mixed at room temperature for 10 minutes to obtain a mixture.

Example 2. Addition of thistle root residue

The procedure was the same as in Example 1, except that the roots of thistles were extracted in hot water when preparing the thistle powder, and the remaining residue was dried and pulverized to obtain C powder (root residue powder), and then the A powder, B powder, and C powder were prepared. After mixing (A powder + 0.3 parts by weight of C powder with respect to 100 parts by weight of B powder) to prepare a mixed extract powder of thistle, a composition was prepared using this.

Comparative Example 1. Using only thistle extract

It was carried out in the same manner as in Example 1, but only the thistle extract was used without using the mixed extract.

Comparative Example 2. Different proportions of thistle

1 part by weight of flowers of thistle and 11 parts by weight of a mixture of stems and leaves (stem: leaf = 1:2 weight ratio) were mixed and extracted in hot water at 95 ° C for 24 hours to obtain an extract A, followed by 1.0 parts by weight of thistle root at 95 ° C. Extract B was obtained by extraction with hot water for 24 hours, and then lyophilized to prepare A powder and B powder, respectively, and mixed to prepare a mixed extract powder.

Comparative Example 3. Omitting Useul

It was carried out in the same manner as in Example 1, but the usul was not used when preparing the mixed extract.

Comparative Example 4. Omit arrowroot

It was carried out in the same manner as in Example 1, but kudzu was not used when preparing the mixed extract.

Comparative Example 5. Sewage omission

It was carried out in the same manner as in Example 1, but sewage was not used when preparing the mixed extract.

Comparative Example 6. Omit ginger

It was carried out in the same manner as in Example 1, but ginger was not used when preparing the mixed extract.

<Test Example>

Test Example 1. Confirmation of estrogen receptor (ER) agonist activity

The biological action of estrogen is mediated by the binding of estrogen to the estrogen receptor (ER) as a ligand, and since the ER acts as a transcription factor and binds to ERE (estrogen response element), an ERE reporter, that is, ER-reactive luciferin It is known that the effect of a therapeutic agent can be monitored by confirming ER-mediated transcriptional activity using the enzyme. Therefore, in order to examine whether the mixture prepared according to Examples and Comparative Examples of the present invention can act as an ER agonist to improve menopausal symptoms caused by estrogen deficiency in menopausal women, transfection with a plasmid containing ERE-luciferase After each sample was treated in one cell, the degree of ER-mediated transcriptional activity was measured.

Specifically, the estrogen receptor-positive breast cancer cell line MCF-7 purchased from the American Type Culture Collection (ATCC) was cultured in RPMI 1680 medium with non-essential amino acids, antibiotics/antimycotics, and sodium pyruvate. Cells were cultured using a solution containing sodium pyruvate and 10% fetal bovine serum as a basal medium. They were subcultured once a week on average. 48 to 60 hours (2-3 days) before cell seeding, serum was treated with dextran-charcoal three times, and it contained stripped serum containing phenol-red. The cells were cultured using a medium prepared with RPMI 1680 without. This medium was continuously used until the end of the luciferase assay. The reason for using the medium is to exclude the estrogen properties of phenol-red itself and the result of estrogen receptor interaction by hormones and growth factors contained in serum in large amounts.

Then, the cultured breast cancer cell line MCF-7 was inoculated (10 ⁵ cells/well) in a 24-well plate one day before transfection, and then ERE-luciferase plasmid DNA (0.25 μg/well) was added to Lipofectamine 2000 The breast cancer cell line was transfected using a transfection reagent (Invitrogen). Then, E2 (17β-estradiol) (ER agonist, 1 nM, Sigma) and ICI 182,780 (Pure ER antagonist, 1

μM, Tocris) was used. E2 and ICI were dissolved in ethanol. In addition, the sample was tested at a concentration of 500 μg/ml. The final amount of ethanol did not exceed 0.2% of the medium volume, and it was confirmed through independent experiments that this amount of ethanol did not affect the final experimental results at all. On the other hand, samples and controls were treated with cells and cultured for an average of 18 to 24 hours, and then luciferase assay was performed. After removing the medium, the cells were incubated with cold PBS for 2 hours. After washing twice, the cell-soluble material (lysate) was extracted with 1X passive lysis buffer (Promega), and 50 μl of the cell-soluble material was added with 50 μl of luciferase assay reagent (including luciferin, which is the substrate of luciferase, and a buffer suitable for enzymatic reaction). After mixing the solution, Promega), the generated luminescence intensity was measured using SpectraMax M5e (Molecular Device).

division relative luciferase activity ethanol 3.1 E2 (1 nm) 100 E2+ICI 12.4 500 μg/mL Example 1 76.9 Example 2 82.4 Comparative Example 1 14.8 Comparative Example 2 17.7 Comparative Example 3 21.6 Comparative Example 4 23.5 Comparative Example 5 19.7 Comparative Example 6 24.0

As shown in Table 1 above, since the mixtures prepared according to Examples 1 and 2 of the present invention have a superior degree of ER-mediated transcriptional activity compared to the positive control group and Comparative Examples 1 to 6, the mixtures of Examples 1 and 2 It was confirmed that it had estrogenic activity and exhibited an excellent activity as an ER agonist.

Therefore, the mixture of Examples 1 and 2 can be used for female hormone replacement therapy for preventing and treating menopausal symptoms caused by estrogen deficiency in menopausal women.

Hereinafter, formulation examples of the composition containing the powder of the present invention will be described, but the present invention is not intended to limit them, but only to be specifically described.

Formulation Example 1. Preparation of powder

500 mg of mixture powder obtained in Example 1

Lactose 100 mg

Talc 10 mg

A powder is prepared by mixing the above ingredients and filling them in an airtight bag.

Formulation Example 2. Preparation of tablets

300 mg of mixture powder obtained in Example 1

Corn Starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

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

Formulation Example 3. Preparation of capsule formulation

200 mg of mixture powder obtained in Example 1

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium stearate 0.2 mg

Capsules are prepared by mixing the above ingredients and filling them into gelatin capsules according to a conventional capsule preparation method.

Formulation Example 4. Preparation of Injections

600 mg of mixture powder obtained in Example 1

Mannitol 180 mg

Sterile Distilled Water for Injection 2974 mg

Na ₂ HPO _4, 12H ₂ O 26 mg

It is prepared with the above component content per 1 ampoule according to the conventional method for preparing injections.

Formulation Example 5. Preparation of liquid formulation

4 g of mixture powder obtained in Example 1

Isomerized sugar 10 g

5 g mannitol

Appropriate amount of purified water

According to the conventional liquid formulation manufacturing method, each component is dissolved in purified water, lemon flavor is added in an appropriate amount, the above components are mixed, and then purified water is added to adjust the total amount to 100g, and then filled into a brown bottle to be sterilized. to prepare a liquid.

Formulation Example 6. Preparation of granules

1,000 mg of mixture powder obtained in Example 1

Appropriate amount of vitamin mixture

Vitamin A Acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

10 μg of biotin

Nicotinamide 1.7 mg

Folic acid 50 μg

Calcium Pantothenate 0.5 mg

Appropriate amount of mineral mixture

Ferrous sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium Carbonate 25.3 mg

Potassium Phosphate Monobasic 15 mg

Dibasic Calcium Phosphate 55 mg

Potassium citrate 90 mg

Calcium Carbonate 100 mg

Magnesium Chloride 24.8 mg

Although the composition ratio of the above vitamin and mineral mixture was prepared by mixing ingredients suitable for granules in a preferred embodiment, the mixing ratio may be arbitrarily modified, and after mixing the above ingredients according to a conventional granule manufacturing method, It can be prepared and used for preparing a health functional food composition according to a conventional method.

Formulation Example 7. Manufacturing of functional beverages

1,000 mg of mixture powder obtained in Example 1

Citric Acid 1,000 mg

100 g of oligosaccharides

2 g plum concentrate

1 g of taurine

Add purified water to total 900 mL

After mixing the above ingredients according to the normal health drink manufacturing method, stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered and collected in a sterilized 2 L container, sealed and sterilized, and then refrigerated. It is used for preparing the functional beverage composition of the present invention.

Although the composition ratio is a mixture of ingredients suitable for a relatively favorite beverage in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the class of demand, the country of demand, and the purpose of use.

Claims (5)

milk thistle hydrothermal extract; and
A pharmaceutical composition for the prevention or treatment of female menopausal symptoms, characterized in that it contains as an active ingredient; a mixed hot water extract obtained by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, sage and ginger. The method of claim 1, based on 100 parts by weight of the thistle hot water extract, 5 to 30 parts by weight of hyussul, 100 to 150 parts by weight of kudzu, 5 to 30 parts by weight of aronia, 5 to 30 parts by weight of pomegranate, 5 to 30 parts by weight of sewage And a pharmaceutical composition for preventing or treating female menopausal symptoms, characterized in that mixed with 1 to 20 parts by weight of ginger. The pharmaceutical composition for preventing or treating female menopausal symptoms according to claim 1, wherein the mixture of flowers, stems and leaves of thistles, and roots of thistles are mixed in a weight ratio of 1: 14-25: 0.1-0.9. . The method of claim 1, wherein the female menopausal symptoms include hot flashes, sweating, dry skin, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, dysuria, urgency, concentration disorder, short-term memory disorder, anxiety, nervousness, memory A pharmaceutical composition for preventing or treating female menopausal symptoms, characterized in that at least one selected from the group consisting of decline, muscle pain, joint pain and osteoporosis. milk thistle hydrothermal extract; and
A food composition for the prevention or improvement of female menopausal symptoms, characterized in that it contains as an active ingredient; a mixed hot water extract obtained by extracting a mixture consisting of wooseul, kudzu, aronia, pomegranate, sewage and ginger.