KR101931226B1 - Composition for preventing, alleviating or treating disorder associated with polycystic ovary syndrome comprising extract of Cassiae Semen as effective component - Google Patents

Abstract

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

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases,

The present invention relates to a composition for preventing, ameliorating or treating a polycystic ovary syndrome-related disease comprising an extract of Cassiae Semen 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.

On the other hand, Cassia tora (Cassiae Semen) is second Cassia tora (Cassia obtusifolia L.) or Cassia tora L., which is an annual plant belonging to the soybean family. It is dried in the fall and the seeds are collected and collected by the next stem. The taste is sweet and spicy, and the quality is a bit cold. It cleanses the liver, clears the eyes, brightens the eyes, has a diuretic effect, dilutes the stools, and works well for the stool. It is used when the eyes are red due to hepatic fever or wind heat, and when they are sick or teary when they are swollen, they are blended with 夏白草, 梔子, mulberry leaves etc. . In addition, constipation due to heat or bowel dryness caused by constipation can be boiled, eaten, or made into powder, lowering blood pressure or lowering blood cholesterol.

As a prior art relating to the use of the herbal extract of the present invention, Korean Patent Publication No. 2002-0084871 discloses a composition for hormone replacement therapy containing an extract of Lolium japonicus as an active ingredient, Korean Patent Publication No. 2017-0004328 There is known a composition for treating or preventing a mental disease caused by stress containing a Cercanal extract. However, a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases containing the Cercanal extract of the present invention as an active ingredient is not known .

The present invention provides a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases comprising the Cassiae japonica extract as an active ingredient, wherein the Cassiae japonica extract of the present invention contains androgen DHEA Dehydroepiandrosterone), and has the effect of reducing the ratio of luteinizing hormone / follicle stimulating hormone, increasing follicular stimulating hormone, and decreasing the number of ovarian follicular cysts , The present invention has been completed.

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

In addition, the present invention provides a health functional food composition for preventing or ameliorating polycystic ovary syndrome-related diseases, which comprises an extract of Cetus luteum as an active ingredient.

The extract of the present invention has an activity of regulating the production of androgen DHEA (Dehydroepiandrosterone), and has an effect of decreasing the luteinizing hormone / follicle stimulating hormone ratio, increasing the follicular stimulating hormone and ovarian follicular cyst, It can be effectively used for preventing, ameliorating or treating one or more diseases selected from hyperandrogenemia related to polycystic ovary syndrome, amenorrhea, premature menstruation, dysfunctional uterine bleeding, premature menopause, obesity, ovarian failure and endometriosis have.

FIG. 1 shows the results of confirming the effect of the extract of Cassiae 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 shows the effect of reducing the luteinizing hormone (FSH) / luteinizing hormone (FSH) ratio in a polycystic ovary syndrome (PCOS) animal model of the present invention. It is the county.
FIG. 3 is a graph showing the increase effect of FSH on the polycystic ovary syndrome (PCOS) animal model of the present invention.
FIG. 4 is a graph showing the effect of reducing the cystic follicle of the present invention on an animal model of polycystic ovary syndrome (PCOS).

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

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

(1) extracting an extractant 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 in an amount of 1 to 20 times the weight of the dried cuticle, 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 Cassiae Extract, it 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.

In addition, the present invention relates to a health functional food composition for preventing or ameliorating polycystic ovary syndrome-related diseases, which comprises an extract of Cercariae 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 Cassiae 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 foods to which the Cassiae Extract of the present invention can be added include meat products, sausages, breads, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including 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 food may contain various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, alginic 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

The killer used in the embodiment of the present invention is purchased and used by the killer distributed in the country.

2. Control of Androgen DHEA (Dehydroepiandrosterone) Production

In one embodiment of the present invention, in order to confirm whether or not the human adrenal gland cell line (H295R) is treated with 10 μM Forskolin to increase the production of androgen DHEA (Dehydroepiandrosterone) and reduce the amount of increased androgen DHEA, 50 [mu] g / ml and 100 [mu] g / ml of the ethanol extract of the killer were 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 (FSH) and ovarian follicular cyst counts of the luteinizing hormone (FSH) (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 Cassiae Extract

The Cassiae Extract of the present invention was obtained by adding 10 times 70% (v / v) ethanol to the amount of the dried Cassiae sample and leaching at 80 ° C for 3 hours. The above-obtained Cassiae Extracts were filtered with a 5 탆 filter of a qualitative filter paper, concentrated by a vacuum rotary vacuum concentrator, and lyophilized using a freeze dryer.

Example  2. The androgen DHEA of the killer extract ( dehydroepiandrosterone ),

As shown in FIG. 1, it was confirmed that the production of androgen DHEA (dehydroepiandrosterone) was inhibited to a significant level by treatment with human adrenal cell line (H295R) at a concentration of 50 μg / ml and 100 μg / ml.

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

(PCOS) group treated with 1 mg / kg / BW letrozole and group treated with 1 mg / kg / BW letrozole and 300 mg / kg / BW grouper (PCOS + 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, Were administered.

As shown in FIG. 2, 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) (LH / FSH ratio) of the luteinizing hormone / follicle stimulating hormone ratio (LH / FSH ratio) was significantly increased in the group treated with 300 mg / kg / ratio significantly decreased (FIG. 2).

Example  4. Follicular stimulating hormone (Follicular Stimulation Hormone) FSH ) Change confirmation

Using an animal model, changes in the content of follicular stimulating hormone were observed. The content of follicular stimulating hormone decreased significantly in the PCOS-induced group of 1 mg / kg / BW letrozole, and the experimental group (300 mg / kg / BW) PCOS < / RTI > + cleanser) showed a statistically significant increase in follicular stimulating hormone (Fig. 3).

Example  5. Ovariectomy through administration of Cetus extract 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, the number of cystic follicles of ovarian cysts was significantly increased in the PCOS-induced animal model group, (PCOS + recipient), the number of ovarian cysts was significantly reduced (FIG. 4).

Claims (8)

A pharmaceutical composition for preventing or treating polycystic ovary syndrome comprising an extract of Cassiae Semen 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 Cassiae 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 Cassiae Extract. A health functional food composition for preventing or ameliorating a polycystic ovary syndrome-related disease, which comprises an extract of Cercariae 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. [7] The composition of claim 6, wherein the composition is prepared from one of powder, granule, ring, tablet, capsule, candy, syrup and beverage.

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