KR20170140592A - Composition for treating or preventing postmenopausal syndrome containing honey berry - Google Patents

Abstract

The present invention relates to a composition for treating, ameliorating, or preventing climacterium in women containing a honey berry extract as an active ingredient. According to the present invention, the composition for treating, ameliorating, or preventing climacterium in women contains, as the active ingredient, the honey berry extract which is not harmful to human body without side effects, and also ensures excellent therapeutic effects on climacterium, thereby being useful for treating or ameliorating climacterium.

Description

Technical Field [0001] The present invention relates to a composition for treatment or prevention of female postmenopausal syndrome including honeyberry extract as an effective ingredient. [0002]

The present invention relates to a composition for the treatment, improvement or prevention of female postmenopausal syndrome comprising a composition for treatment, improvement or prevention of female postmenopausal syndrome, specifically a component derived from a natural product.

Women go through a series of sexual maturation as they get older. This period is called puberty. This refers to a process in which an individual's physical structure and emotions reach a state where they can fulfill their original functions. After puberty, women secrete estrogen and progesterone, the female hormones. Specifically, when the gonadotropin secreted by the pituitary gland transfers a signal, it regulates the menstrual cycle and regulates the fertilization of the hormone Folliocle Stimulating Hormone (FSH) and Lutenizing Hormone (LH) ), And the follicle-stimulating hormone and the luteinizing hormone act on the ovary again to secrete estrogen and progesterone.

The estrogen is a hormone secreted from the follicles in the ovary. It promotes the development of the reproductive organs and functions to develop secondary sex and promotes uterine growth, endometrial hyperplasia, development of the mammary gland, regular menstruation, and the like. In addition to the ovaries, the estrogen is secreted in a small amount from the adrenal cortex and testes, including the placenta. Three kinds of steroids such as estrone, estradiol and estriol found in the human body are known.

Among the above estrogens, 17 beta-estradiol (E2), the most abundant and strongest estrogen in women before menopause, is synthesized while producing follicles and secreted into the blood to partially bind sex hormone-binding globulin and flow to cells throughout the body . The main pathway of the estradiol metabolism is that the estradiol is reversibly oxidized to estrone (E1) which is a weak estrogen and then converted to estriol (E3).

The estrogen stimulates the growth of endometrium, uterine muscle, vagina and urethral epithelium, smoothes vascular flow in the reproductive tract, increases secretion of uterine glands, and induces progesterone and luteinizing hormone receptor expression. In addition to the development of female reproductive organs and secondary manifestations, the estrogen affects skeletal growth and development, female fat distribution and lipid metabolism, and also acts on skin and collagen tissues, neurons and cardiovascular system.

In women, the function of the ovaries declines with age, and this leads to a significant decrease in estrogen secretion. Due to the reduced secretion of estrogen, the response to follicle-stimulating hormone and luteinizing hormone is reduced, the initial follicle shortening is shortened, the menstrual cycle is further shortened, the ovulation phase is further shortened, and progesterone production is reduced. Eventually, the follicle becomes unresponsive and does not produce estrogen.

It is known that climacteric is a transitional period in which physiological function and sexual function are reduced or eliminated due to an overall and gradual decrease of ovarian function, and ovulation is stopped after ovarian function is stopped as a part of menopausal period, A permanent stop is called menopause. On the other hand, the World Health Organization (WHO) defined menopause as a period when ovarian function is lost and estrogen secretion is no longer conceived, and that the transition from adulthood to old age is over.

As described above, women gradually start ovarian function gradually from the age of 40 after the menopausal period, and the average life span of women is gradually extended, the period of hormone deficiency is about 1/3 to half of the life span. Thus, there is an increasing need for special attention to the healthy life of women after menopause.

For example, in Korea, the proportion of elderly people aged 65 or older is estimated to be 9.1% in 2005, and it is expected to be more than 14% of the population in 2019. The average life expectancy of women is higher than that of men In 2002, the average life span of women was 80.4 years. Therefore, women in Korea should live for about 40 years after menopause. In this respect, interest in women's health after menopause is increasing .

The chronic chronological symptoms due to changes in the body during the menopausal period, including the menopause or previous menstrual changes due to changes in hormones, specifically estrogen production, follicle stimulating hormone and luteinizing hormone, are called menopausal symptoms or menopausal symptoms.

In particular, the decrease in estrogen affects not only the female urinary system, genitalia but also other parts of the body, so estrogen secretion decreases greatly throughout the body.

For example, most menopausal women are experiencing acute female hormone deficiency symptoms such as hot flush, tachycardia, sweating, anxiety or sleep disorder, and some women have chronic cardiovascular disease, menopausal syndrome And chronic diseases such as hypertension.

Specifically, symptoms of menopausal symptoms include symptoms due to vascular changes such as hot flush, night sweat, tachycardia or headache, and symptoms due to musculoskeletal changes such as myalgia, joint pain and back pain , Memory loss, depression, loss of concentration, anxiety, and dizziness.

In addition, since the estrogen is reduced, the supply of blood is not smoothly performed and the elasticity and moisture of the skin and vaginal mucosa are lost. For example, when the mucous membranes of the eyes, nose, or mouth are dry, they may experience uncomfortable eyes or thirsty burns.

In addition, symptoms such as vaginal dryness, urinary tract infections, urinary frequency or urinary incontinence appearing within several years of menopause and epidermal symptoms, menopausal syndrome, atherosclerosis or cerebrovascular disease such as atherosclerosis . In particular, heart disease is one of the major causes of death in postmenopausal women, and many women suffer from menopausal syndrome due to rapid bone loss due to postmenopausal estrogen deprivation.

As described above, the necessity of treatment for postmenopausal women is becoming more and more important, and various methods have been studied for the treatment of the symptoms of postmenopausal women, namely, postmenopausal syndrome. For the treatment of postmenopausal syndromes, Hormone Replacement Therapy (HRT), which administers estrogen, is widely used.

There are two types of estrogen: natural estrogen and synthetic estrogen. Oral administration is the most widely used method of administering the synthetic estrogen hormone preparation, and parenteral administration includes transdermal patches, transdermal cream, gel, and vaginal cream.

However, such an artificial synthetic estrogen is effective for the improvement of the menopausal symptoms, but it increases the activity of the cancer-inducing gene in the long-term use, thereby posing a risk of uterine cancer or breast cancer and possibly causing venous thrombosis or gallbladder disease. Is being heated.

Accordingly, studies have been made actively to find a estrogen derived from a natural product having a similar activity to a synthetic estrogen as a substitute for the synthetic estrogen used in the above-mentioned hormone replacement therapy, while having a less side effect.

Premarin, made from natural product-derived estrogens and from the animal's natural urine, has been shown to increase the levels of estradiol and estrone in clinical trials to a monthly level. However, there have been reports of serious side effects such as increased breast cancer (26%), heart attack (29%) and fainting (44%), and blood coagulation (2 times) It ended itself in five years, and the US Food and Drug Administration (FDA) decided in 2003 to put a warning on hormone medicines.

Although the use of conventional hormone replacement agents such as synthetic estrogen and animal estrogen products can cope with overall menopausal symptoms, there is a problem that their use is limited due to serious side effects.

Therefore, there is a trend toward research on natural estrogen derived from plant having a similar activity to synthetic estrogen as a substitute for synthetic estrogen used in the above-mentioned hormone replacement therapy and having less side effects.

In particular, plant-derived natural estrogens are often referred to as phytoestrogens.

The vegetable estrogen refers to a non-steroidal compound derived from a plant which is generally similar in function and structure to female hormone estrogen, and is found in the stem, root, flower or seed of a plant.

Examples of the above vegetable estrogens include isoflavone derived from soybean and bean, coumestan derived from clover, and lignan derived from flax seed. In addition, there are flavanones, flavones, dihydrocalchones, and the like.

For example, isoflavones exist as inactive glycosides of biochanin A and formononetin in plants, but are absorbed into the body and are similar to estrogen by glucosidase in intestinal bacteria (Genistein) and daidzein (daidzein), resulting in estrogen-like activity.

Genistein, which is a representative example of the vegetable estrogen, has been reported to inhibit the protein tyrosine kinase of cells and thus to inhibit the growth of cancer cells. However, it has also been reported that it may cause cancer in people who have no effect or who have a genetic predisposition for uterine cancer and breast cancer.

Therefore, it is required to develop new phytoestrogenic estrogens having excellent estrogenic activity without side effects such as the side effects of genistein. Due to this necessity, it is urgently required to objectively verify the natural resources that have been used for a long time as a food and have proved its safety, and to develop a natural substance having a therapeutic, improving or preventive effect on female postmenopausal syndrome.

10-1067028B 10-1075554B 10-1141194B 10-0934022B

In order to solve the above problems, it is an object of the present invention to provide a composition for treating, ameliorating or preventing a female postmenopausal syndrome, which comprises a natural product effective for treating, preventing or ameliorating a female postmenopausal syndrome .

In order to achieve the above object, the present invention provides a composition for treating or preventing female menopausal syndrome. The composition for treating or preventing female menopausal syndrome may be a pharmaceutical composition or a pharmaceutical composition.

More specifically, the present invention provides a pharmaceutical composition for the treatment or prevention of female postmenopausal syndrome comprising honeybear extract as an active ingredient.

The honeyberry extract may be a honeyberry extract, and the solvent extract of the honeyberry may be a solvent extract, preferably a hot water extract, extracted with water, an alcohol having 1 to 5 carbon atoms, or a mixture thereof.

The female postmenopausal syndrome may be facial flushing or venous thrombosis.

The pharmaceutical composition for the treatment or prevention of female menopausal syndrome may further contain estrogen in addition to the honeyberry extract.

The present invention also provides a food composition for improving or preventing female postmenopausal syndrome comprising honeybear extract as an active ingredient.

The honeyberry extract may be a honeyberry extract, and the honeyberry extract may be a solvent extract, preferably a hot water extract, which is extracted with water, an alcohol having 1 to 5 carbon atoms, or a mixture thereof.

The female postmenopausal syndrome may be facial flushing or venous thrombosis.

The food composition for improving or preventing the female menopausal syndrome may further include estrogen in addition to the honeyberry extract.

The food composition for improving or preventing female menopause syndrome may be a health functional food for improving or preventing female menopausal symptoms.

The inventors of the present invention have long been used as foods for the development of phytoestrogens which exhibit excellent estrogenic activity but do not cause side effects such as synthetic estrogens or animal estrogens used in conventional hormone replacement agents and toxicity In studying its safety-proven natural resources, it has been shown that the extracts of Swallowtail tree, specifically the honeyberry extract of the royal thyme, have activity or effect similar to estrogen activity in human breast tissue-derived cell line MCF-7 cells , And further confirmed that it has an activity or effect similar to that of estrogen activity through animal experiments, thus completing the present invention.

As used herein, unless otherwise specified, the active ingredient refers to a component that provides a therapeutic, ameliorative, or preventive effect, particularly an estrogen-like or estrogen-like activity, in a composition, particularly a pharmaceutical composition or a food composition, of a female postmenopausal syndrome do.

As used herein, the term " extract " means an extract obtained by treating an extractive solvent with a plant or a product prepared by the method of producing an extract, unless otherwise specified. The extract may be formulated ) Results.

The extract has the meaning of being used as a crude extract, but broadly includes fractions obtained by further fractionating the extract. Specifically, the above-mentioned extract includes not only an extract obtained by using an extraction solvent, but also an extract obtained by additionally applying a purification process thereto. For example, the extract may contain a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, a fraction obtained by various chromatographies (prepared for separation according to size, charge, hydrophobicity, or affinity) Further comprising fractions obtained through various purification methods.

Unless otherwise specified herein, a pharmaceutically effective amount means an amount sufficient to exert pharmacological efficacy.

Unless otherwise specified herein, estrogen is a female hormone that is mainly secreted in the follicles and progesterone in the ovary of an animal, and is also secreted in the placenta and affects the reproductive cycle. The estrogen is a steroid hormone with a benzene ring and is chemically very stable. Three kinds of estrone (E1), estradiol (E2) and estriol (E3) are well known. Since estrogen directly affects the reproductive cycle, it can be used as a treatment for abnormalities in menstruation, in contraceptive pills, and because menopause or menopausal syndrome is caused by estrogen deficiency when women become menopausal, It may also be used in hormone therapy for the treatment or prevention of disorders or postmenopausal syndromes.

The estradiol is a steroid hormone secreted from the female ovary of vertebrate animals. It is one of the follicle hormones (estrogenic hormones). It enters the cell nucleus and promotes the synthesis of new proteins, causes cell proliferation, Estrogen is mainly estradiol, a female hormone that is marketed as a medicament for the treatment or prevention of uterine growth disorder, menopausal disorder, or menopausal syndrome. For example, estradiol, which is commercially available as the above-mentioned medicines, includes the overhormones, the peranin, the feminin, and the proginone.

As used herein, unless specified otherwise, menopausal syndrome or menopausal symptoms refers to symptoms resulting from a decrease in hormone production in postmenopausal women, and generally includes facial flushing, sweating, sweating during sleep, dry skin, vaginal dryness, vaginal dryness It is a concept that includes atrophy, lower urinary tract atrophy, sexual intercourse, vaginitis, cystitis, dysuria, urinary incontinence, intensive impairment, short term memory impairment, anxiety, nervousness, memory loss, libido, myalgia, arthralgia or menopausal syndrome.

Unless otherwise specified herein, treatment or amelioration refers to any action in which administration of the composition of the present invention improves or alleviates symptoms of female postmenopausal syndrome.

As used herein, " prophylactic " means any action that inhibits the symptoms of female postmenopausal syndrome by administration of the composition of the present invention, unless otherwise specified herein.

In this specification, unless otherwise indicated, administration means to provide any desired composition of the invention to the subject by any suitable method.

As used herein, unless otherwise specified, an individual refers to any animal, particularly a mammal, including humans, monkeys, dogs, goats, pigs or rats, who have undergone female polyneuropathy syndrome by administration of the composition of the present invention.

Unless otherwise specified herein, a pharmaceutically effective amount means an amount sufficient to treat a female menopausal syndrome at a reasonable benefit or risk ratio applicable to medical treatment, including the type, severity, severity of a female postmenopausal syndrome, The activity of the compound, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, the factors including the drugs used simultaneously and other factors well known in the medical arts.

Hereinafter, the present invention will be described in more detail.

The present invention relates to a method for producing Lonicera The present invention relates to a pharmaceutical composition for the treatment or prevention of female postmenopausal syndromes, which comprises extracts of honeycomb, caerulea , preferably honey berry, as an active ingredient.

The lobster ( Lonicera) caerulea there is. edulis ) is a dicotyledonous plant of Capricornia (Caprifoliaceae). It is a cold-temperate plant mainly distributed in Siberia, Sakhalin, northern China, Tibet, North Korea and others. The honey berries, which are the fruits of the above-mentioned leaves, have been used as traditional medicinal plants in northern China, Siberian indigenous people and Japan due to their efficacy against liver disease. However, relatively few studies have been conducted in North America and Europe, Is known to have an effect on ischemic brain diseases.

The honeyberry is known to contain an antioxidant-rich anthocyanin, flavonoid and low-molecular phenolic acids, and is known to have anti-inflammatory, wound healing promoting effect, skin protection effect against ultraviolet rays, lipid And glucose metabolism improvement effect and liver protection effect. In addition, studies on the domestic honeyberry have not been carried out other than studies related to liver health, and there are many related products, and the results are also disclosed about liver ginseng, antioxidant activity or antiinflammation, but estrogen- There is little known about the effects of improving or treating menopausal symptoms.

In addition, the honeyberry is listed as an edible fruit in the food ingredient database (DB) of the Food and Drug Administration, so it is considered that it will not be a hindrance to the development of a health food or a pharmaceutical product in the future

The honeyberry extract may be prepared according to a conventional method for producing plant extracts. For example, the honeyberry extract may be prepared by extracting honeyberry, its dried product or its pulverized product or its juice with an extraction solvent, or extracting it with an extraction solvent And may be one prepared by fractionating a crude extract with a fraction solvent.

The honeyberry is not limited to harvested, cultivated or marketed, and the honeyberry can be used at any stage during the growing stage.

The method for preparing the above extract can be produced by a conventional method for producing a plant extract, specifically a solvent extraction method, a supercritical extraction method, a subcritical extraction method, a high temperature extraction method, a high pressure extraction method or an ultrasonic extraction method, Resin. ≪ / RTI > The adsorption resin may be, for example, XAD or HP-20. The method for preparing the extract may be, for example, a solvent extraction method.

The solvent extraction method may be a heat extraction method, a cold extraction method, a warm-up extraction method, or the like, and a conventional extraction device, an ultrasonic pulverizing extractor, a supercritical extractor, a subcritical extractor or a fractionator may be used.

In the case of preparing the honeyberry extract by the solvent extraction method, the extraction solvent used in the solvent extraction method may be any one selected from the group consisting of water, an organic solvent, and a combination thereof, and the organic solvent preferably has 1 to 5 carbon atoms Alcohol, diluted alcohol, ethereal solvent such as ethyl acetate or acetone, nonpolar solvent such as ether, chloroform, benzene, hexane or dichloromethane, or a mixed solvent thereof. The alcohol having 1 to 5 carbon atoms may be methanol, ethanol, propanol, butanol, isopropanol and the like, but is not limited thereto. The alcohol-diluted water may be diluted with water in an amount of 50% (v / v) to 99.9% (v / v) of alcohol.

The extraction solvent of the honeyberry extract of the present invention may preferably be at least one selected from the group consisting of water, an alcohol having 1 to 5 carbon atoms, an alcohol-diluted water, and a mixture thereof, more preferably water, Alcohol, and mixtures thereof, and still more preferably, water. The extraction process may be performed at, for example, 50 ° C to 150 ° C, or 75 ° C to 120 ° C, or 80 ° C to 100 ° C, but is not limited thereto. The extraction time is not particularly limited, but may be 10 minutes to 24 hours, or 30 minutes to 12 hours, or 2 hours to 5 hours.

The extract may be a fraction prepared by extracting with an extraction solvent or extracting with an extraction solvent and fractionating the extract with a fraction solvent.

The fraction is extracted with an extraction solvent and extracted with any one solvent selected from the group consisting of hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water and mixtures thereof, preferably hexane, methylene chloride and ethyl acetate And the fractionation process is further carried out with at least one solvent selected from the group consisting of Two or more kinds of solvents may be used for the fractionation, and fractions of each extract may be prepared by sequentially using them or by mixing them according to the polarity of the solvent.

The fractionation process may be performed, for example, at 4 ° C to 120 ° C, or 50 ° C to 90 ° C, or 60 ° C to 80 ° C, but is not limited thereto.

The honeyberry extract or the fraction obtained by performing the fractionation process may be filtered, concentrated or dried to remove the solvent, and may be subjected to both filtration, concentration and drying. Specifically, the filtration can be performed using a filter paper or a vacuum filter, and the concentration can be reduced by using a vacuum concentrator, for example, a rotary evaporator. The drying can be performed by, for example, freeze drying.

The honeyberry extract may be, for example, a powdery form obtained by putting honeyberry in an extraction container together with an extraction solvent, extracting and filtering the resultant and concentrating under reduced pressure and freeze-drying again. The extracts obtained can be stored in a deep freezer until use.

In addition, the honeyberry extract has been used for a long time as a food material as a natural product separated from a natural plant or a processed product of the same, and is listed as a foodable fruit in a food raw material database (DB) of the Food and Drug Administration, It was confirmed that it did not matter.

In this aspect, the honeyberry extract can be used for the treatment or prevention of female postmenopausal syndrome. From this viewpoint, the honeyberry extract can be used as an active ingredient of a pharmaceutical composition for treating or preventing female menopausal syndrome of an extract.

The composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient can be directly applied to animals including humans.

The term postenopausal syndrome refers to all symptoms caused by a decrease in estrogen not only in menopause but also in perimenopausal and postmenopausal periods.

The full-blown competition is a period before the actual menopause starts. During the entire menopausal period, the generation of estrogen is irregular, and the fertility of the woman is greatly reduced. The full-closed event may last for several months or several years, and climacteric symptoms may occur in the full-closed event.

The menopausal syndrome may be selected from the group consisting of sexual intercourse, vaginal dryness, sleep disorder, mental awareness problem, arthralgia, musculoskeletal disease, dyspepsia, urinary incontinence, fatigue, , Climacteric symptoms such as night sweats, palpitations, depression, anxiety, and irritability, and further include severe diseases or conditions caused by estrogen deficiency, such as menopausal syndrome Hyperlipidemia, cardiovascular disease, dementia, tooth loss or skin collagen loss, and the like.

The female menopausal syndrome is preferably any one selected from the group consisting of facial flushing and venous thrombosis.

The composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient may contain the honeyberry extract in an amount of 0.1% by weight to 50% by weight based on the total weight of the composition, but is not limited thereto.

The composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of medicaments.

The composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., oral preparations, suppositories and sterilized injection solutions according to a conventional method have.

Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

When the composition of the present invention is formulated, it may be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.

Solid formulations for oral administration of the compositions of the present invention include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium Calcium carbonate, sucrose or lactose, gelatin, and the like. In addition to the above excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration of the composition of the present invention include suspensions, solutions, emulsions, syrups and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, Preservatives, and the like.

Formulations for parenteral administration of the composition of the present invention may include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the agent for parenteral administration include non-aqueous solvents, suspensions such as propylene glycol, vegetable oils such as polyethylene glycol, olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The composition for the treatment or prevention of female menopausal symptoms comprising the honeyberry extract as an active ingredient may be a composition containing the honeyberry extract alone as an active ingredient or a material having a therapeutic or preventive effect on women's menopausal symptoms in the honeyberry extract as an active ingredient .

Specifically, the composition for treating or preventing female menopausal symptoms comprising the honeyberry extract of the present invention as an active ingredient further comprises a compound having a therapeutic or preventive effect for a known female postmenopausal syndrome or an extract for a natural product .

More specifically, the pharmaceutical composition for treating or preventing the female menopausal syndrome may further include estrogen in addition to the honeyberry extract. The estrogen can be, for example, estradiol.

The composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient may contain, in addition to the above-mentioned effective ingredients, additional ingredients such as pharmaceutically acceptable or nutritionally acceptable carriers, excipients, A diluent or a subcomponent.

More specifically, the composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient may further comprise, in addition to the active ingredient, a nutrient, a vitamin, an electrolyte, a flavoring agent, a colorant, a thickening agent, a pectic acid or a salt thereof, And a salt thereof, an organic acid, a protective colloid thickener, a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated drink, and the like. The carrier, excipient or diluent may be selected from lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acicia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline In the group consisting of celluloses, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, But the present invention is not limited thereto. Any conventional carrier, excipient or diluent may be used. The components may be added to the active ingredient, i.e., honeyberry extract, either independently or in combination.

The composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient may contain 0.0001 to 99% by weight, preferably 0.01 to 30% by weight, of the effective ingredient, specifically the honeyberry extract, To 50% by weight, and more preferably 0.1% by weight to 30% by weight.

When the composition for treating or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient is weakly formulated, it may contain conventional fillers, extenders, binders, disintegrators, surfactants, anti-coagulants, lubricants, wetting agents, Or preservatives, and they can be used either orally or parenterally.

The formulation of a composition for the treatment or prevention of female menopausal syndrome comprising the honeyberry extract as an active ingredient may be in a form suitable for the method of use depending on the method of use and may be a form that provides rapid, sustained or delayed release of the active ingredient By using a method known in the art. Examples of the specific formulations include granules, powders, syrups, liquids, suspensions, tablets, injections, main tablets, cataplasma, capsules, soft or hard gelatin capsules and the like.

Further, a composition for treating or preventing female menopausal syndrome comprising the honeyberry extract as an active ingredient can be prepared using a suitable method known in the art or by using the method described in Remington's Pharmaceutical Science (recent edition), Mack Publishing Company, Easton PA). ≪ / RTI >

The dosage of the composition for treatment or prevention of female postmenopausal syndrome comprising the honeyberry extract according to the present invention as an active ingredient may vary depending on factors such as the formulation method, administration method, age, sex and weight of the recipient, severity of disease, Route, excretion rate, responsiveness, and the like. For example, a composition for treating or preventing female menopausal symptoms comprising the honeyberry extract of the present invention as an active ingredient may be administered at a daily dose of 0.0001 mg / kg to 1000 mg / kg or 0.01 mg / kg To 100 mg / kg or 30 mg / kg to 50 mg / kg. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

The composition for improving or preventing female menopausal symptoms according to another embodiment of the present invention contains honeyberry extract as an active ingredient. Since the honeyberry extract has been experimentally confirmed to have excellent estrogenic activity and has been used for a long time as a food material of food and its stability is not a problem, the honeyberry extract can be used for the improvement or prevention of female postmenopausal syndrome. From this viewpoint, the honeyberry extract can be used as an active ingredient of a food composition for improving or preventing female menopausal symptoms of an extract.

The composition for improving or preventing female menopausal symptoms includes a honeyberry extract as an active ingredient, and a composition for improving or preventing a female postmenopausal syndrome.

The menopausal syndrome may be selected from the group consisting of sexual intercourse, vaginal dryness, sleep disorder, mental awareness problem, arthralgia, musculoskeletal disease, dyspepsia, urinary incontinence, fatigue, , Climacteric symptoms such as night sweats, palpitations, depression, anxiety, and irritability, and further include severe diseases or conditions caused by estrogen deficiency, such as menopausal syndrome Hyperlipidemia, cardiovascular disease, dementia, tooth loss or skin collagen loss, and the like.

The female menopausal syndrome is preferably any one selected from the group consisting of facial flushing and venous thrombosis.

The composition for improving or preventing female menopausal symptoms comprising the honeyberry extract as an active ingredient may be a composition containing the honeyberry extract as an active ingredient alone or a material having an effect of improving or preventing female menopausal syndrome in the honeyberry extract, In addition to the honeyberry extract, it may further contain a compound having an effect of improving or preventing a known female postmenopausal syndrome or an extract for a natural product.

More specifically, the food composition for improving or preventing the female menopausal syndrome may further include estrogen in addition to the honeyberry extract.

In addition, the food composition for improving or preventing female menopause syndrome may be a health functional food for improving or preventing female menopausal symptoms.

The term " food " means a natural product or a processed product containing one or more nutrients, preferably a state of being able to be eaten directly through a certain degree of processing, Beverages, food additives, beverage additives, and the like.

Such foods include, for example, various foods, beverages, gums, tea, vitamin complexes, and health functional foods. In addition, in the present invention, the food may contain special nutritional foods (e.g., crude oil, spirits, infant food, etc.), meat products, fish products, tofu, jelly, noodles (Such as soy sauce, soybean paste, hot pepper paste, mixed sauce), sauces, confectionery (eg snacks), dairy products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods (E.g., fruit, vegetable beverages, two-oil beverages, fermented beverages, etc.), seasonings (e.g., ramen soup, etc.). The food, the health functional food, the beverage, the food additive and the beverage additive can be produced by a usual production method.

The above-mentioned health functional food refers to a food group to which the function of the food is added to a specific purpose by physical, biochemical, and biotechnological techniques, and to control the bio-defense rhythm of the food composition, Means a food which has been designed and manufactured so that the weight control function related to the living body is sufficiently expressed to the living body.

The health functional food may include food-acceptable food supplementary additives, and may further include suitable carriers, excipients and diluents conventionally used in the production of health functional foods.

The drink refers to a generic term for eliminating thirst or drinking to enjoy a taste, and is intended to include a health functional drink. The beverage may contain various flavors or natural carbohydrates as an additional ingredient, such as ordinary beverages, without any particular limitation, except that the beverage contains the honeycomb extract as an essential ingredient at an indicated ratio as an active ingredient. have.

Examples of such natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and Xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate may be generally about 1 to 20 g, or 5 to 12 g per 100 ml of the food composition of the present invention. In addition, the composition of the present invention may be used for the production of natural fruit juice, fruit juice drink, Can also be added.

In addition to the above, the food composition of the present invention can be used as a flavoring agent such as a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. These components can be used independently or in combination. The proportion of such an additive is not so important, but may be selected from the range of 0 to 200,000 parts by weight per 100 parts by weight of the honeyberry extract of the present invention, but is not limited thereto.

The health-functional beverage is used to control the bio-defense rhythm of the beverage group or beverage composition to which the added value is imparted so that the function of the beverage functions for a specific purpose by physical, biochemical, biotechnological, or the like, Means a beverage which has been designed so as to sufficiently express the body controlling function related to the living body.

The health functional beverage is not particularly limited to the other ingredients except for containing the honeyberry extract of the present invention as an essential ingredient in the indicated ratio and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages .

Examples of such natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and xylitol , Sorbitol, and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably 5 to 12 g per 100 ml of the composition of the present invention.

The present invention also provides a food composition for improving or preventing female menopausal symptoms comprising honeyberry extract as an active ingredient, wherein the effective ingredient may be contained in an amount of 0.0001% by weight to 10% by weight of the total food, In a proportion of 0.00002 g to 5 g.

Since the estrogenic activity of the honeyberry extract of the present invention has been confirmed in the experimental results, the hormone replacement therapy to prevent, alleviate or treat menopausal syndromes such as facial flushing and venous thrombosis caused by estrogen deficiency in postmenopausal women therapy, HRT), and unlike conventional treatments for postmenopausal syndromes, safety is not a problem, and the honeyberry is low in side effects and safe to be used as a food, It has an excellent effect as compared with the therapeutic agent for the disease.

FIG. 1 is a graph showing the estrogenic activity of the honeyberry extract according to an embodiment of the present invention. FIG. 1 is a graph showing the degree of cell growth of MCF-7 using an E-screen assay. In the graph, And the vertical axis represents the degree of absorption, that is, the degree of cell growth, measured on the basis of the positive control group.
FIG. 2 is a graph showing the estrogen-like activity of the honeyberry extract according to an embodiment of the present invention, wherein the abscissa indicates the concentration of the treated extract, and the ordinate indicates the concentration of chloramphenicol acetyltransferase (CAT) And the content of Chloramphenicol acetyltransferase (CAT) protein measured based on the positive control group.
FIG. 3 is a graph showing the estrogen-like activity of the honeyberry extract according to an embodiment of the present invention, and is a graph showing changes in the content of estradiol according to the administration of the honeyberry extract in an experimental animal. In the graph, And the vertical axis represents the measurement result of estradiol content in blood.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

All data in the examples of the present invention are presented as mean ± EM from five or more independent experiments. Statistical significance of differences between groups was calculated using the Student's two tailed t-test.

< Example  One. Honeyberry  Preparation of Extract>

The honeyberry extract was prepared as follows.

Specifically, the honeybee purchased from the domestic was purchased, washed three times in the running water to remove impurities, and then the honeybee was lyophilized for 24 hours at a temperature of -3 ° C to -5 ° C , And pulverized by a pulverizer to prepare a honeyberry pulverized product.

1 L of water or 20% ethanol aqueous solution was added to 100 g of the crushed honeyberry, and the mixture was homogenized. After the mixture was extracted at 90 ° C for 3 hours, the mixture was concentrated under reduced pressure at 60 ° C using a rotary vacuum concentrator. The concentrated honeycomb extracts were each sterilized using a filter cloth of 400 mesh filter, and then lyophilized at -70 ° C to prepare a powdery crude extract. The crude extract was dissolved in distilled water to prepare a sample of each honeyberry extract. The sample of the honeyberry extract prepared above was stored at -20 ° C. until use. The extracts were dried and stored at -20 ° C until use.

< Example  2. Honeyberry  Estrogenic activity of the extract Measure 1 >

In order to measure the estrogenic activity of the berry extract, a sample was first prepared. 17β-estradiol (E8875-1G, Sigma, USA) was diluted with ethanol at a concentration of 10 ^-10 M and then diluted with a solvent. The honeyberry extract was prepared by adding the two kinds of honeyberry extract and honeyberry extract prepared in Example 1 to MCF-7 cell culture medium for human breast-derived cancer cells (DMEM / F12 (11330-032, GIBCO, USA) + 10 10 μg / ml, 50 μg / ml, and 100 μg / ml in a solution containing 1% FBS (26140-111, GIBCO, USA) + 1% Penicillin Streptomycin (15140-122, GIBCO, USA) + 1% Bovine insulin ml, 250 μg / ml, 500 μg / ml, 750 μg / ml, 1000 μg / ml and 2000 μg / ml, respectively.

MCF-7 cells were cultured in a culture medium (DMEM / F12 (11330-032, GIBCO, USA) + 10% FBS (26140-111, GIBCO, USA) + ATCC (American Type of Cell Culture) 1% Penicillin Streptomycin (15140-122, GIBCO, USA) + 1% Bovine insulin (Cellapplications, USA)). After the culture, the cells were seeded in 96 well plates at a concentration of 5 × 10 ³ cells / 100, and then cultured in a 5% CO ₂ incubator at 37 ° C. for 24 hours. The medium was exchanged after the first two days and then every four days thereafter. After 2 to 3 days of culture, when the primary cultured cells reached a density of 70 to 80%, they were subcultured using a 0.025% trypsin solution.

Estrogenic activity was analyzed by E-screen assay. The subcultured MCF-7 cells were cultured in a 96-well culture plate at 5 × 10 3 cells / well for 24 hours, and cultured in a fresh DMEM culture medium (5% charcoal + 0.5% dextran + 5% FBS (26140-111, GIBCO, USA) + 1% penicillin-streptomycin). Thereafter, the two honeycomb extracts and the honey extract were added to a final concentration of 10 μg / ml, 50 μg / ml, 100 μg / ml, 250 μg / ml, 500 μg / ml, 750 μg / ml, (RBI, Natick, Mass., USA) was used as a positive control. As a negative control, 20% ethanol was used instead of the extract, And then grown for 6 days. Cell growth was measured by sulfordamine-B (SRB) assay.

The degree of cell growth was performed in the following manner.

First, the culture medium was removed, washed twice with PBS, and 500 μl of 10% trichloroacetic acid (TCA) was added thereto. The cells were allowed to stand at 4 ° C for 30 minutes to fix the cells to the bottom of the plate. After the cell fixation, the plate was washed 5 times with distilled water to completely remove the remaining TCA solution and dried at room temperature to remove residual water. The completely dried plate was stained with 300 μl of 1% acetic acid solution in 0.4% SRB solution for 15 minutes, and then washed 5 times with 1% acetic acid to remove excess SRB . The stained cell plates were dried at room temperature, and 1 ml of 10 mM trisma base (pH 10.5) was added to each well. The staining solution was eluted with a microplate reader (Bio-Rad, Benchmark, Hercules, CA, USA) And the absorbance at 550 nm was measured. The measurement results are shown in Fig.

As shown in FIG. 1, MCF-7 cells proliferated in a concentration-dependent manner at a concentration of less than 1000 μg / ml in both the honeyberry extract and the juice. In both the honeyberry extract and the juice solution, And showed an activity of 20% or more as compared with the negative control (honeyberry 0 μg / ml concentration).

In addition, estrogen-like activity measurement was performed using the MCF-7 cells.

The estrogen-like activity assay was performed by washing the cultured MCF-7 cells for assay of estrogen analogues with 1X phosphate buffered saline (PBS) when the cell density reached about 90% confluence, and then cultured in fresh DMEM (2% FBS) . Three kinds of honeyberry extract (juice, hot water, and ethanol extract) were added to final concentrations of 10, 50, 100, 250, 500, 750, 1000 and 2000 μg / ml. As a standard substance, estrogen- -estradiol (RBI, Natick, MA, USA) was dissolved in 100% ethanol to a final concentration of 10 ^-10 M and treated with ethanol instead of the extract as a negative control. After incubation at 37 ° C in a 5% CO ₂ incubator for 48 hours, the cells were recovered, washed twice with 1 × PBS, and centrifuged at 3000 × g for 5 minutes to remove the supernatant. After the addition of 250 μl of 1X lysis buffer, the cells were suspended and allowed to stand at room temperature for 30 minutes. Then, using the CAT-ELISA kit (Roche Applied Science, Mannheim, Germany) And the content thereof was measured. The CAT protein content was normalized to the total protein content of each extract as determined by the BCA protein assay reagent kit (Pierce, Rockford, Ill., USA). The results of the protein content measurement are shown in FIG.

As shown in FIG. 2, both the honeyberry extract and the juice showed estrogen-like activity in a concentration-dependent manner at a concentration of less than 1000 μg / ml. In both the honeyberry extract and the juice solution, (0 μg / ml concentration of honeyberry).

< Example  3. Honeyberry  Estrogenic activity of the extract Measure 2 >

Sixty-eight-week-old SPF female virgin Kwl (ddY mice, Kiwa Laboratory Animal, Japan), a total of 80 rats, were weighed at 20 ° C After 9 days of purging in a breeding room where temperature of 25 ° C, relative humidity of 40% to 45%, and light cycle of 12 hours each were controlled, it was adapted. During the breeding period, feeds (Samyang, Korea) and water were available at all times.

Out of the 80 rats, 72 rats underwent ovariectomy (OVX surgery), and 8 rats underwent sham surgery to identify the gonad and re-suture the abdomen. The ovariectomized operation was performed in a state where the animal was intraperitoneally injected with Zoletile (Virbac Lab., France) anesthetics at 25 mg / kg bw. In addition, the Sham operation was performed by exposing both ovaries and suturing the skin again without removing the ovaries.

After the animals that had undergone the surgery were recovered, eight mice were selected for each group, and an article treatment was performed for 84 days after the 28 days of OVX surgery. Daily. Among the above samples, the honeybee extract group administered 10 mg, 20 mg and 40 mg of each of the two kinds of honeyberry hot water extracts based on 1 kg of the body weight of the experimental animals, and the honeyberry juice was weighed 1 kg 40 mg was administered as a standard, and the drug control was subcutaneously administered to the dorsal skin only at the same dose of sterilized distilled water instead of the honeyberry extract.

Group Treatment The control (sham control) Sham Surgery + Distilled Water Treatment OVX control (OVX control) Induction of menopausal syndrome by ovariectomy + distilled water treatment The drug control (Risedronate) Ovariectomy induced menopausal syndrome + 17b-estradiol (0.03 ug / head) Honeyberry 400 (BHa 400) Induction of menopausal syndrome by ovariectomy + honeyberry hot water extract 400 mg / kg bw / oral administration Honeyberry 200 (BHa 200) Induction of menopausal syndrome by ovariectomy + honeyberry hot water extract 200 mg / kg bw / oral administration Honeyberry 100 (BHa 100) Induction of menopausal syndrome by ovariectomy + honeyberry hot water extract 100 mg / kg bw / oral administration Honeyberry ethanol 400 (BHm 400) Induction of menopausal syndrome by ovariectomy + aqueous solution of honeyberry ethanol 400 mg / kg bw / oral administration Honeyberry ethanol 200 (BHm 200) Induction of menopausal syndrome by ovariectomy + aqueous extract of honeyberry ethanol 200 mg / kg bw / oral administration Honeyberry ethanol 100 (BHm 100) Induction of menopausal syndrome by ovariectomy + aqueous solution of honeyberry ethanol solution 100 mg / kg bw / oral administration Harbinberry juice 400 (BHi 400) Induction of menopausal syndrome by ovariectomy + honeyberry juice 400 mg / kg bw / oral administration

After 84 days in the experimental animals, the blood was taken and the content of estradiol in the blood was measured. The results are shown in FIG.

As shown in FIG. 3, in the OVX control group, there was a significant decrease in the serum estradiol content (p <0.01) as compared with the control group. However, in all the experimental groups including BHm 400 mg / kg, <0.01), respectively. Especially, BHj group showed similar increase of serum estradiol level compared with BHa group, and BHm group showed similar or better serum estradiol content than BHa group Respectively.

In the OVX control group, the serum estradiol content was -75.85%, whereas the BHj 400 mg / kg, BHa and BHm 400, 200 or 100 mg / kg groups showed 204.74, 49.60, 50.79 , 38.98, 27.67, 52.77, 43.08 and 31.66%, respectively.

< Manufacturing example >

Hereinafter, a preparation example of a pharmaceutical composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

Manufacturing example  One. Sanje  Produce

Honeyberry extract 500 mg

Lactose 100 mg

10 mg of talc

The above components are mixed and filled in airtight bags to prepare powders.

Manufacturing example  2. Preparation of tablets

Honeyberry extract 500 mg

Corn starch 100 mg

Lactose 100 mg

2 mg of magnesium stearate

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Manufacturing example  3. Preparation of capsules

Honeyberry extract 500 mg

Corn starch 100 mg

Lactose 100 mg

2 mg of magnesium stearate

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Manufacturing example  4. Preparation of injections

Honeyberry extract 500 mg

Sterile sterilized water for injection

(2 ml) per ampoule in accordance with the usual injection method.

Manufacturing example  5. Liquid  Produce

Honeyberry extract 100 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Manufacturing example  6. Manufacture of health food

Honeyberry extract 1000 mg

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

24.8 mg of magnesium chloride

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Manufacturing example  7. Manufacture of health drinks

Honeyberry extract 1000 mg

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 ° C for about 1 hour. The resulting solution was filtered and sterilized in a 2-liter sterile container. The resulting solution was refrigerated, And used in the preparation of the composition.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Manufacturing example  8. Manufacture of beverages

Honey 522 mg

5 mg &lt; RTI ID = 0.0 &gt;

Nicotinic acid amide 10 mg

3 mg of sodium riboflavin hydrochloride

Pyridoxine hydrochloride 2 mg

Inositol 30 mg

Orthoic acid 50 mg

0.48 to 1.28 mg of honeyberry extract

200 ml of water

A beverage was prepared using the above-mentioned composition and content by a conventional method.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (7)

A pharmaceutical composition for the treatment or prevention of female postmenopausal syndrome comprising honeybear extract as an active ingredient. The method according to claim 1,
Wherein the honeyberry extract is a honeyberry hot-water extract. The method according to claim 1,
Wherein the female menopausal syndrome is facial flushing or venous thrombosis. 4. The method according to any one of claims 1 to 3,
A pharmaceutical composition for the treatment or prevention of female menopausal syndrome, which comprises estrogen. A food composition for improving or preventing a female postmenopausal syndrome comprising honeybear extract as an active ingredient. 6. The method of claim 5,
Wherein the honeyberry extract is a honeyberry hot-water extract. 6. The method of claim 5,
The food composition for improving or preventing female menopause syndrome is a health functional food for improving or preventing female postmenopausal syndrome.

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