KR101874458B1 - Composition for preventing, improving or treating disorder associated with polycystic ovary syndrome comprising extract of Tetragonia tetragonoides as effective component - Google Patents
Composition for preventing, improving or treating disorder associated with polycystic ovary syndrome comprising extract of Tetragonia tetragonoides as effective component Download PDFInfo
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- KR101874458B1 KR101874458B1 KR1020170048332A KR20170048332A KR101874458B1 KR 101874458 B1 KR101874458 B1 KR 101874458B1 KR 1020170048332 A KR1020170048332 A KR 1020170048332A KR 20170048332 A KR20170048332 A KR 20170048332A KR 101874458 B1 KR101874458 B1 KR 101874458B1
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- extract
- polycystic ovary
- ovary syndrome
- preventing
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Abstract
The present invention relates to a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases comprising an effective amount of a first herbal extract as an active ingredient, wherein the first extract of the present invention is an active ingredient for controlling the production of androgen DHEA (Dehydroepiandrosterone) Luteinizing hormone, blood testosterone, and ovarian follicular cyst have been reported to be effective in the treatment of polycystic ovarian syndrome related diseases such as hyperandrogenemia, amenorrhea, hypometasia, dysfunctional uterine bleeding, premature menopause , Obesity, ovarian failure, and endometriosis. ≪ Desc / Clms Page number 2 >
Description
The present invention relates to a composition for preventing, ameliorating, or treating a polycystic ovary syndrome-related disease comprising an effective amount of a first herb extract.
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, a study of age and weight showed that the luteinizing hormone (LH) hypersecretion in serum, insulin resistance, and compensation were significantly lower in women with polycystic ovary syndrome (50% 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, Seonjangcho is a perennial plant that grows in the sandy seaside of the beach. The stem grows or stands diagonally. Its length is 40-50cm. Leaves are alternate and thick. Petioles are about 2cm long. Blade is egg-shaped triangle or oval, 4-6cm long, 3-5cm wide. Flowers bloom in 1-2 axes from the beginning of April to the end of November, and calyx tubules are shallowly divided into 4-5 branches, with green on the outside and yellow on the inside. There are no petals, the fruit is nuts, and there are thorn like projections on the upper part. The young leaves eat herbs and use the outposts as medicines. It is native to southern Korea, Ulleungdo and Jeju Island, and is distributed in Japan, China, South Asia, Australia, North America and South America. It is used for the treatment of gastroenteritis, gastric ulcer, stomach cancer, uterine cancer, swelling of the skin, swelling caused by infestation by the oil hole, and so on. The outpost contains abundant iron, calcium, vitamin A and various vitamin B.
The prior art extracts of the present invention have been reported in Korean Patent No. 0483183, which is known to have a cell death inhibitory activity and a pharmaceutical composition containing the same. However, Compositions for preventing, ameliorating or treating polycystic ovary syndrome-related diseases are not known.
Accordingly, the present invention provides a composition for preventing, ameliorating or treating polycystic ovary syndrome-related diseases comprising the extract of Opadonthiasis as an active ingredient. The present invention also provides a composition for preventing, The present invention has been accomplished by confirming that there is an effect of regulating the production of androgen DHEA (Dehydroepiandrosterone) and reducing the number of blood luteinizing hormone, blood testosterone and ovarian follicular cyst.
In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases comprising Tetragonia tetragonoides extract as an active ingredient.
The present invention also provides a health functional food composition for preventing or ameliorating polycystic ovary syndrome-related diseases comprising Tetragonia tetragonoides extract as an active ingredient.
The present invention relates to a composition for preventing, ameliorating, or treating a polycystic ovary syndrome-related disease comprising an effective amount of a first herb extract. Since the extract of the present invention is effective for regulating the production of androgen DHEA (Dehydroepiandrosterone) and has an effect of reducing the number of luteinizing hormone, testosterone and ovarian follicular cyst in the blood, It can be widely used in the related medicines such as amenorrhea, amenorrhea, dysmenorrhea, uterine bleeding, premature menopause, and fever, which are related to polycystic ovary syndrome.
FIG. 1 shows the results of confirming the effect of the 70% (v / v) ethanol extract of the present invention using the human adrenal gland cell line (H295R) (Progressive E) to produce androgen DHEA (Dehydroepiandrosterone). Con is a control group, the cells are untreated, FOR is a group of cells treated with 10 μM of Forskolin to induce an over secretion of androgens, MET is a group of positive control cells treated with 1 mM metformin And PIO is a positive control cell treated with 10 [mu] M pioglitazone. *** indicates that the production of androgen DHEA was significantly increased in cells treated with phoscholine compared to Con, which means that p <0.001, and #, # indicates the increase in dehydroepiandrosterone (DHEA) ) Were statistically significantly decreased by the treatment with the first-time extract of the present invention and metformin, respectively, where # is p <0.05 and ## is p <0.01.
2 is a result of western blot analysis of the effect of the progeny extract of the present invention on the production of androgen DHEA (Dehydroepiandrosterone) using the human adrenal gland cell line (H295R).
FIG. 3 is a graph showing the effect of reducing the luteinizing hormone in the PCOS animal model by administering the antiprotozoal extract according to the present invention to an animal model of PCOS. PCOS + TTG500 is the group of administration of letrozole and prothodontic extract, PCOS + MET is the group of letrozole and metformin metformin) was administered. * Indicates a statistically significant increase in luteinizing hormone in letrozole-treated group compared to CON, indicating that p <0.05, and # indicates that when administered in combination with letrozole, The luteinizing hormone of the administration group or the metformin administration group was statistically significantly decreased, and # is p <0.05.
FIG. 4 is a graph showing the effect of reducing the testosterone in the blood by administering the antiprotozoal extract according to the present invention to an animal model of PCOS. PCOS + TTG500 is a group of administration of letrozole and prothodontic extract, PCOS + MET is a group of letrozole, and PCOS + MET is a testosterone- And metformin. ≪ / RTI > * Indicates a statistically significant increase in testosterone in letrozole-treated group compared to CON, which means p <0.05, and # indicates that the testosterone-treated group of letrozole- The statistically significant decrease in testosterone in the group treated with the extract of metazonoside or metformin was found to be p <0.05.
The present invention relates to a process for preparing Tetragonia The present invention also relates to a pharmaceutical composition for preventing or treating polycystic ovary syndrome-related diseases, which comprises an extract of tetragonoides as an active ingredient.
The progeny extract can be prepared by a method including, but not limited to, the following steps:
(1) extracting by adding an extraction solvent in advance;
(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 dry weight of the first step, more preferably 5 to 15 times, and further preferably 10 times by weight. The extraction temperature is preferably 4 to 50 ° C, but is not limited thereto. The extraction time is preferably 10 to 100 hours, but is not limited thereto. 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. The polycystic ovary syndrome-related disease is preferably one or more selected from hyperandrogenemia, amenorrhea, hypometasia, dysfunctional uterine bleeding, premature menopause, fever and endometriosis. But is not limited to.
In addition to the herbal extract, the 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 select the intraperitoneal, rectal, rectal, intravenous, intramuscular, subcutaneous, intrauterine or intracerebral injection methods during parenteral administration, It is preferably used for external skin application.
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 invention also tetragonia tetragonioides (Tetragonia The present invention relates to a health functional food composition for preventing or ameliorating a polycystic ovary syndrome-related disease, which comprises, as an active ingredient, a tetragonoides extract.
The polycystic ovary syndrome is characterized by ovarian failure, and the ovarian failure-related disease is preferably one or more selected from hyperandrogenemia, amenorrhea, hypometasia, dysfunctional uterine bleeding, premature menopause, obesity and endometriosis. It does not.
The health functional food composition for preventing or ameliorating ovarian failure-related diseases which comprises the extract of the present invention as an active ingredient may be prepared by any one of powder, granule, ring, tablet, capsule, candy, syrup and beverage, And can be suitably produced according to a conventional method.
Examples of the food to which the extract of the present invention can be added include a dairy product including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, 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
In the embodiment of the present invention, the first step is to purchase and distribute the first-step picked or distributed in Jeju Island.
1. 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, The ethanol extract of 70% (v / v) of 50 μg / ml of pre-treatment was treated with 1 mM of metformin (MET) and 10 μM of pioglitazone (PIO) as a positive control.
On the other hand, the degree of expression of CYP17A1, p-CREB, p-ERK and ERK protein in the adrenal cell line (H295R) treated with the above substances was confirmed by Western blot (Fig. 2).
2. Establishment of an animal model of polycystic ovary syndrome (PCOS) and confirmation of control of luteinizing hormone and blood testosterone contents
Female SD rats used as experimental animals were supplied by Du-Yeol Biotech. Experimental animals were adapted for 7 days at SPF (Specific pathogen free) facility of Korea Research Institute of Oriental Medicine, and then PCOS induction group as a control group, PCOS induction group as a control group and metformin ) Treated group (PCOS + MET), PCOS induced group and PCOS + TTG500 treated group.
Experimental methods were carried out at the Korea Institute of Oriental Medicine (16-087), and the animals were maintained and maintained at 23 ± 1 ℃ and humidity Five (5) animals were placed in an IVC (individually ventilated cage) in a feeding room kept constant at 50 ± 10% and 12 hours of light intensity.
In order to confirm whether the progeny extract of the present invention reduces the content of luteinizing hormone and testosterone, an animal model of polycystic ovary syndrome (PCOS) was established.
In this method, daily oral administration of 1 mg / kg / BW of letrozole for 21 days (0d-21d) induces symptoms of PCOS. As a positive control, 500 mg / kg / BW metformin ) And the 500 mg / kg / BW first-time extract of the present invention were used to alleviate PCOS symptoms by oral administration for a total of 28 days (0d-28d).
After the experiment, the animals were anesthetized and blood was collected from the inferior vena cava and centrifuged (5,000 rpm, 10 min) to obtain serum. Serum luteinizing hormone was measured by enzyme immunoassay, and blood testosterone was also measured by enzyme immunoassay (Abcam, Cambridge, UK) according to the manufacturer's protocol.
Example One. Early spring Preparation of extract
In the present invention, the fresh shoots were purchased from Jeju Island, South Korea, and used. The dried seedlings were added with 10 times 70% (v / v) ethanol and leached at room temperature for 48 hours. ≪ / RTI > The obtained first-time extract was filtered with a 0.4 mu m filter, concentrated using a vacuum rotary condenser, and lyophilized using a freeze dryer.
Example 2. Early spring Extract of androgen DHEA ( 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. Metformin showed a similar effect on the production of androgen DHEA (Dehydroepiandrosterone) in the experimental group treated with 1mM metformin. Metformin, however, decreased the insulin resistance and regulated blood glucose level in patients with polycystic ovary syndrome, It is also known that it can cause degradation phenomenon.
Meanwhile, it was confirmed that the contents of CYP17A1, p-CREB, p-ERK and ERK proteins, which are known to regulate androgen DHEA (dehydroepiandrosterone), decreased in the cells treated with the progeny extract of the present invention (FIG.
Example 3. Serum luteinizing hormone ( luteinizing hormone reduction effect
Using the PCOS animal model, changes in the content of luteinizing hormone in the blood were observed. In the group administered with PCOS-induced 1 mg / kg / BW letrozole, the amount of luteinizing hormone in the blood was statistically significantly increased, and the test group containing 500 mg / kg / BW Tetragonia tetragonoides extract of the present invention (PCOS + TTG500) and 1 mg / kg / BW letrozole were used in combination with 500 mg / kg / metformin (PCOS + MET) 3).
Example 4. Reduction of blood testosterone
Using the PCOS animal model, changes in serum testosterone content were determined. In PCOS-induced
Example 5. Ovary I'm a cyst Effect on number
As shown in Table 1, the effects of the extract of letrozole alone (PCOS) or the mixture of letrozole and metformin (PCOS + MET), the number of ovarian oocysts in the experimental group (PCOS + TTG500) treated with the mixture of the extract of letrozole and letrozole was significantly decreased.
* P < 0.05 versus CON, # P < 0.05 versus PCOS
Claims (8)
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020170048332A KR101874458B1 (en) | 2017-04-14 | 2017-04-14 | Composition for preventing, improving or treating disorder associated with polycystic ovary syndrome comprising extract of Tetragonia tetragonoides as effective component |
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| KR1020170048332A KR101874458B1 (en) | 2017-04-14 | 2017-04-14 | Composition for preventing, improving or treating disorder associated with polycystic ovary syndrome comprising extract of Tetragonia tetragonoides as effective component |
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| KR101874458B1 true KR101874458B1 (en) | 2018-07-05 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR100673538B1 (en) | 2005-10-04 | 2007-01-24 | 재단법인 제주하이테크산업진흥원 | Tetragonia tetragonoides essential oil extracts having antimicrobial activity |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100673538B1 (en) | 2005-10-04 | 2007-01-24 | 재단법인 제주하이테크산업진흥원 | Tetragonia tetragonoides essential oil extracts having antimicrobial activity |
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