KR20190043920A - Composition for preventing, alleviating or treating disorder associated with polycystic ovary syndrome comprising extract of Glycyrrhizae Radix et Rhizoma as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating polycystic ovary syndrome-related diseases containing an extract of Glycyrrhiza uralensis as an active component. The extract of Glycyrrhiza uralensis of the present invention has an activity of regulating the production of androgen dehydroepiandrosterone (DHEA) and testosterone, an effect of reducing a luteinizing hormone/follicle stimulating hormone ratio, an effect of increasing follicle stimulating hormone in blood, and an effect of reducing a number of ovarian follicular cysts, thereby being effectively used for preventing, alleviating, or treating one or more diseases selected from hyperandrogenemia, amenorrhea, hypomenorrhea, dysfunctional uterine bleeding, premature menopause, infertility, ovarian failure, and endometriosis, which are polycystic ovary syndrome-related diseases.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases comprising an extract of licorice as an active ingredient.

The present invention relates to a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases comprising an extract of licorice (Glycyrrhizae Radix et Rhizoma) as an active ingredient.

Polycystic ovary syndrome is an endocrine metabolic disease in which 4-12% of women are affected. In 1990, the criteria for diagnosis of polycystic ovary syndrome presented by the National Institutes of Health required both chronic anovulation and clinical or biochemical hyperandrogenemia. On the other hand, the 2003 European / American Association for the Reproductive Endocrinology Society (FSEE) has three diagnostic criteria: chronic anovulation, clinical or biochemical hyperandrogenemia, and the appearance of 10 small follicles along the edge of the enlarged ovary Polycystic ovary syndrome is defined as two or more of the criteria.

The cause of polycystic ovary syndrome has yet to be clarified. Like other complex diseases, the genetic and environmental factors are thought to be responsible for the onset of polycystic ovary syndrome. As the technique of the study develops, the focus of primary pathophysiology is shifting from the ovaries to the hypothalamic-pituitary axis, and then to the defects of insulin action. Although studies on the association of various genetic factors with polycystic ovary syndrome have been reported, there are no clinically applicable genetic tests yet.

Symptoms of polycystic ovary syndrome include (1) oligomenorrhea or amenorrhea, (2) androgen and hyperandrogenism and / or hyperandrogenemia, (3) polycystic ovary morphology )to be. In addition, based on a study of age and weight, about 50% of women with polycystic ovary syndrome showed luteinizing hormone hypersecretion, insulin resistance, and compensatory hyperinsulinemia And biochemical features such as compensatory hyperinsulinemia are common.

An example of polycystic ovary syndrome related diseases is premature ovarian failure, which occurs when the ovarian function is not functioning normally. It is classified as ovulatory cycle irregularity, luteal dysfunction, and anovulation cycle irregularity do. Anovulatory sex donation is physiologically present in puberty and menopausal age but becomes infertile in mature women. Lung dysfunction leads to rapid degeneration of the luteal function, causing infertility and abortion. The ovulation cycle irregularity is considered to be due to the abnormality of the length of the irregularity because it is more than the length of the cycle. This ovarian failure is basically an age-related increase in menopause symptoms may appear as a period of menopause, abnormally below 40 years of age, such symptoms may occur in pregnancy difficulties. If symptoms worsen in this condition, it leads to premature menopause.

In addition, it is caused by dysfunction of the gonadal axis leading to hypothalamus-pituitary-ovary caused by a decrease in ovarian function, which causes physical and mental changes such as sex hormone, lipid and cardiovascular metabolism, bone metabolism, and memory function. The onset of menopause begins with menopause, and menopausal women are at risk for many diseases due to hormone imbalance, calcium deficiency and increased oxidative stress in the body. In other words, estrogen change in menopause causes the incidence of diseases such as coronary artery disease, osteoporosis, and Alzheimer to increase rapidly, especially after menopause, estrogen reduction causes rapid bone loss.

Meanwhile, licorice (Glycyrrhizae Radix et Rhizoma) not only makes the human body healthy (脾胃), but also healing the fever of the five ginseng (寒热 邪气) and strengthen the muscles, as well as treat various boils and swelling and all kinds It has an action to detoxify the herb poison, helps the lungs activity, and is a herb that has a great effect of cleansing detoxification. In addition to detoxification of various drugs and poisoning of plants, it has a unique flavor and flavor, so licorice has been used as a basic useful drug in wholesale medicine. The main components of licorice include glycyrrhizin as a sweetener, liquiritin, seokdang, glucose, mannitol, and asparagine, which are flavonoids. In particular, glycyrrhizin is a component that imparts a unique sweetness to licorice.

Prior art related to the use of the medicament containing the licorice extract of the present invention is Korean Patent Laid-Open Publication No. 2017-0055354, which discloses a method for preventing osteoporosis caused by menopause or ovariectomy comprising ginseng extract, peony extract, licorice extract and chitosan as active ingredients Or a therapeutic pharmaceutical composition is known. Korean Patent Laid-Open Publication No. 2016-0093568 discloses a composition for preventing or treating oral diseases, which comprises a process for preparing licorice extract and an extract obtained therefrom, There is no known composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases containing licorice extract as an active ingredient.

The present invention provides a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases comprising an extract of licorice root as an active ingredient. The extract of licorice, which is an effective ingredient of the present invention, contains androgen DHEA Dehydroepiandrosterone and testosterone. It has the effect of decreasing the ratio of luteinizing hormone / follicle stimulating hormone, follicular stimulating hormone and ovarian follicular cyst, The present inventors have completed the present invention.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases comprising an extract of Glycyrrhizae Radix et Rhizoma as an active ingredient.

The present invention also provides a health functional food composition for preventing or ameliorating polycystic ovary syndrome-related diseases comprising licorice extract as an active ingredient.

The licorice extract of the present invention has an activity of regulating the production of androgen DHEA (Dehydroepiandrosterone) and testosterone, and is effective in decreasing the ratio of luteinizing hormone / follicle stimulating hormone in the blood, increasing the follicular stimulating hormone, It is possible to prevent or improve one or more diseases selected from the group consisting of hyperandrogenemia related to polycystic ovary syndrome, amenorrhea, premature menstruation, dysfunctional uterine bleeding, premature menopause, ovarian failure, ovarian failure and endometriosis due to the effect of reducing the number of follicular cysts Can be effectively used for treatment.

FIG. 1 shows the results of confirming the effect of the licorice extract of the present invention on the production of androgen DHEA (dehydroepiandrosterone). FOR (+) is a group of cells treated with 10 μM Forskolin to induce androgen excess.
FIG. 2 is a result of confirming the testosterone-reducing effect of the licorice extract of the present invention. FOR (+) is a group of cells treated with 10 μM Forskolin to induce testosterone overdose.
FIG. 3 is a graph showing the effect of the licorice extract of the present invention on the ratio of luteinizing hormone (LH) / FSH (follicle stimulating hormone) in the polycystic ovary syndrome (PCOS) It is the county.
FIG. 4 shows the effect of the licorice extract of the present invention on an animal model of polycystic ovary syndrome (PCOS) to determine the effect of increasing FSH (follicle stimulating hormone).
FIG. 5 shows the effect of the licorice extract of the present invention on an animal model of polycystic ovary syndrome (PCOS) to determine the effect of reducing the cystic follicle.

The present invention relates to a pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases comprising licorice extract as an active ingredient.

The licorice extract may be prepared by a method including, but not limited to, the following steps:

(1) extracting licorice with an extraction solvent;

(2) filtering the extract of step (1); And

(3) concentrating the filtered extract of step (2) and drying to produce an extract.

In step (1), the extraction solvent is preferably selected from water, a C ₁ -C ₄ lower alcohol or a mixture thereof, more preferably ethanol, even more preferably 70% (v / v) ethanol But is not limited thereto.

In the above production method, any conventional method known in the art such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction may be used. The extraction solvent is preferably added by 1 to 20 times the weight of the dried licorice, more preferably 5 to 15 times, and further preferably 10 times. The extraction temperature is preferably 60 to 100 DEG C, but is not limited thereto. The extraction time is preferably 1 to 48 hours, more preferably 1 to 24 hours, most preferably 3 hours. In the above method, the concentration of the step (3) is preferably, but not limited to, using a vacuum rotary condenser or a vacuum rotary evaporator. In addition, drying is preferably carried out under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, more preferably freeze drying or the like.

The polycystic ovary syndrome is characterized by ovarian failure, and the polycystic ovary syndrome-related disease is preferably one or more selected from hyperandrogenemia, amenorrhea, hypometasia, dysfunctional uterine bleeding, premature menopause, fever and endometriosis. It does not.

In addition to the licorice extract, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier, excipient or diluent.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and it is preferable to use an intravenous or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine, or intracerebral injection method during parenteral administration.

The pharmaceutical composition of the present invention can be prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, " pharmaceutically effective amount " means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

The dosage of the composition of the present invention may be varied depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of disease.

The present invention also relates to a health functional food composition for preventing or ameliorating polycystic ovary syndrome-related diseases comprising licorice extract as an active ingredient.

The polycystic ovary syndrome is characterized by ovarian failure, and the polycystic ovary syndrome-related disease is preferably one or more selected from hyperandrogenemia, amenorrhea, hypometasia, dysfunctional uterine bleeding, premature menopause, fever and endometriosis. It does not.

The health functional food composition for preventing or ameliorating ovarian failure-related diseases containing the licorice extract as an active ingredient may be prepared from any one selected from powders, granules, rings, tablets, capsules, candies, syrups and beverages, And can be suitably produced according to a conventional method.

Examples of the food to which the licorice extract of the present invention can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen and other noodles, gums, ice cream, A tea, a drink, an alcoholic beverage, and a vitamin complex, all of which include health functional foods in a conventional sense.

The health functional foods include various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, alkynic acid and its salts, , pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices and vegetable drinks. These components may be used independently or in combination.

The health functional food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient. The natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are merely illustrative of the present invention and that the scope of the present invention is not limited thereto.

[Samples and Experimental Methods]

1. Sample

Licorice used in one embodiment of the present invention was purchased from licorice distributed in Korea.

2. Control of the production of androgen DHEA (Dehydroepiandrosterone) and testosterone

In one embodiment of the present invention, the human adrenal gland cell line (H295R) is treated with 10 μM of Forskolin to increase the production of androgen DHEA (Dehydroepiandrosterone) and testosterone, and the amount of increased androgen DHEA and testosterone , The licorice ethanol extract was treated.

3. Changes in serum luteinizing hormone / follicle stimulating hormone ratio (LH / FSH ratio), follicular stimulating hormone (FSH) and ovarian follicular cyst

Female SD rats used as experimental animals were supplied from Korea BioLink. The experimental animals were adapted for 7 days at the Korean Animal Research Institute 's co - laboratory.

Experimental methods were reviewed by the Korea Institute of Oriental Medicine Animal Experimental Ethics Committee. Breeding and maintenance of experimental animals were carried out at 23 ± 1 ℃, 50 ± 10% Two rabbits were placed in an IVC (individually ventilated cage) in a constantly maintained incubation room for 12 hours.

Polycystic ovary syndrome (LH / FSH ratio), follicular stimulating hormone and ovarian follicular cyst counts of the licorice extract according to the present invention were examined to determine the number of luteinizing hormone / follicle stimulating hormone (LH / FSH) ratio, follicular stimulating hormone and ovarian follicular cyst (PCOS) Animal models were prepared by injecting a sustained-release pellet with a release of 0.1 mg / kg / day into the subcutis of the rats, followed by oral administration of 1 mg / kg / BW letrozole daily for 2 weeks, Symptoms were induced and established.

Example  1. Preparation of licorice extract

The licorice extract of the present invention was prepared by adding 10 times 70% (v / v) ethanol to the dried licorice sample and leaching at 80 ° C for 3 hours to obtain a licorice ethanol extract. The obtained licorice extract was filtered through a 5 탆 filter with a qualitative filter paper, followed by concentration with a vacuum rotary vacuum concentrator and lyophilization using a freeze dryer.

Example  2. Licorice extract's androgen DHEA ( dehydroepiandrosterone ) And testosterone ( testosterone)  Checking the effect of content adjustment

As shown in FIG. 1, it was confirmed that the production of androgen DHEA (dehydroepiandrosterone) was inhibited to a significant level by treating the human adrenal gland cell line (H295R) with 50 mu g / ml and 100 mu g / ml licorice extract.

In addition, treatment of 1, 10, 50 and 100 mu g / ml of licorice extract with human adrenal cell line (H295R) showed that testosterone Production was inhibited to a significant level.

Example  3. Serum luteinizing hormone / follicle stimulating hormone ratio of licorice extract LH / FSH  ratio change confirmation

(PCOS + licorice) treated with 1 mg / kg / BW letrozole and with 1 mg / kg / BW letrozole and 300 mg / kg / BW licorice extract. PCOS was induced by administering 1 mg / kg / BW letrozole for 2 weeks in the first half of the total experimental period, and PCOS was induced during the second half of the experimental period except for the administration of letrozole, Of licorice extract.

As shown in FIG. 3, in the PCOS group induced by the administration of 1 mg / kg / BW letrozole, changes in blood luteinizing hormone / follicle stimulating hormone (LH / FSH ratio) The ratio of luteinizing hormone / follicle stimulating hormone (LH / FSH ratio) was statistically significantly increased. In contrast, in the group administered with 300 mg / kg / BW licorice extract of the present invention, ratio) significantly decreased.

Example  4. Follicular stimulating hormone (Follicle stimulating hormone) through administration of licorice extract. FSH ) Change confirmation

Using an animal model, changes in the content of follicular stimulating hormone were identified. The dose of follicular stimulating hormone decreased significantly in the PCOS-induced group of 1 mg / kg / BW letrozole, and the dose of 300 mg / kg / BW licorice extract of the present invention PCOS + licorice) showed a statistically significant increase in follicular stimulating hormone (Fig. 4).

Example  5. Administration of licorice extract to ovarian I'm a cyst  Effect on change of number

The number of ovarian cystic follicles was significantly increased in the PCOS-induced animal model group. However, in the case of the administration of 300 mg / kg / BW licorice extract of the present invention (PCOS + licorice), the number of ovarian cysts was significantly reduced (FIG. 5).

Claims (8)

A pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases comprising an extract of Glycyrrhizae Radix et Rhizoma as an active ingredient. The pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases according to claim 1, wherein the solvent of the licorice extract is water, a C ₁ -C ₄ lower alcohol or a mixture thereof. The pharmaceutical composition according to claim 1, wherein the polycystic ovary syndrome is caused by ovarian failure. The method according to claim 1, wherein the polycystic ovary syndrome related disease is at least one selected from hyperandrogenemia, amenorrhea, hypersomnia, dysfunctional uterine bleeding, premature menopause, obesity and endometriosis. A pharmaceutical composition for therapeutic use. The pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases according to claim 1, further comprising a carrier, an excipient or a diluent in addition to the licorice extract. A health functional food composition for preventing or ameliorating polycystic ovary syndrome-related diseases comprising an extract of licorice as an active ingredient. 7. The method according to claim 6, wherein the polycystic ovary syndrome related disease is at least one selected from hyperandrogenemia, amenorrhea, hypersomnia, dysfunctional uterine bleeding, premature menopause, obesity and endometriosis. A health functional food composition for improvement. The ophthalmic composition according to claim 6, wherein the composition is prepared by any one of powder, granule, ring, tablet, capsule, candy, syrup and beverage. Composition.

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