KR102125740B1 - Composition for relieving menopausal symptom comprising Tectorigenin 7-O-xylosylglucoside - Google Patents

Abstract

The present invention relates to a composition for preventing, treating or improving menopausal symptoms, including tectorigenin 7-O-xylosylglucoside. Since the composition according to the present invention has a rapid effect on the prevention, improvement and/or treatment of sweating, facial flushing and/or osteoporosis among female climacteric symptoms, hormone replacement therapy (Hormone replacement) used for the prevention or improvement of conventional menopausal symptoms therapy (HRT).

Description

Composition for relieving menopausal symptom comprising Tectorigenin 7-O-xylosylglucoside}

The present invention relates to a composition for preventing, improving and/or treating menopausal symptoms in women, and more particularly, to a composition effective for preventing, improving and/or treating hot flashes, and/or osteoporosis, among the symptoms of menopause in women. will be.

Menopause in women is a disruption of menstruation that occurs when the function of the genetically determined ovary, which reaches about 50 years after birth, reaches its end of life, means loss of fertility and is a physiological change, not a pathological phenomenon. Currently, the average life expectancy of women in Korea is 81.2 years (2011: Statistics Korea). Assuming that the average menopausal age of Korean women prescribed by the Korean Society for Obstetrics and Gynecology is 50 years old, women's hormones are depleted in about one third of their lifetime. (Seoul National Institute of Pharmacy, Kim Seong-cheol)

As women face menopause, changes in the vasculature, musculoskeletal system, genitourinary system, and brain nerves occur throughout the body due to imbalance and reduction in female hormone secretion. In other words, vasomotor symptoms and psychological symptoms such as hot flashes, night sweats, sleep disorders, fatigue, depression, anxiety, concentration disorders, and memory disorders and loss of skin elasticity due to sexual dysfunction, urinary frequency, collagen reduction, and loss of skin elasticity. Sagging, and various diseases such as cardiovascular and musculoskeletal symptoms and dementia are accompanied (Non-Patent Document 1). Although menopausal symptoms vary from person to person, it has been reported that the quality of life of women decreases as they experience more menopausal symptoms, more severely, and longer periods of time (non-patent document 2). It is highly likely to develop into a chronic disease with aging.

Hormonal therapy, drug therapy, exercise therapy, and dietary therapy may be applied to the treatment of menopausal symptoms, but medically used female hormone therapy may increase the risk of breast cancer, and long-term use of uterine cancer, thrombovascular disease, and gallbladder disease , Can increase the rate of hypertension. Therefore, in recent years, many studies have been conducted on phytoestrogen, which has been reported to function similar to estrogen for the replacement of estrogen therapy and other drug therapies (Non-Patent Document 3).

89% of women who experience natural menopause experience at least one of the symptoms of menopause, and menopausal symptoms are also reported to be common. Accordingly, the present inventors have developed a material capable of effectively improving overall menopausal symptoms and improving facial flushing and osteoporosis caused by menopause, and a composition for preventing or improving symptoms of female menopausal symptoms, including Tectorigenin 7-O-xylosylglucoside. Was completed.

1.J Korean Soc Menopause, 2012, 18: 94-99 2. Women health Noursing, Hyunmoonsa, 1997 3.J East Asian Soc Dietary Life, 2006, 16(5), 533~541

In order to solve the above problems, the present invention is to provide a composition for treating, preventing or improving sweating, hot flashes and/or osteoporosis among female menopausal symptoms.

In addition, the present invention is to provide a composition capable of sustaining the treatment of women's menopausal symptoms and the manifestation of a relief effect.

The present invention provides a composition for preventing, treating or improving menopausal symptoms, including tectorigenin 7-O-xylosylglucoside.

The composition of the present invention may further include tectorigenin, tectoridin, or mixtures thereof.

The Tectorigenin 7-O-Xylosylglucoside has not been known to prevent, treat or improve menopausal symptoms.

In particular, the tectorigenin 7-O-xylosylglucoside has not been known to prevent, treat or improve hot flashes.

The present invention provides a composition for the treatment, prevention or improvement of hot flashes comprising tectorigenin 7-O-xylosylglucoside in one embodiment.

The composition may further include tectorigenin and tectoridine.

In another embodiment, the present invention provides a composition for treating, preventing or improving osteoporosis, comprising tectogenine 7-O-xylosylglucoside.

The composition may further include tectorigenin and tectoridine.

In another embodiment, the present invention provides a composition for treating, preventing or improving sweating comprising tectogenin 7-O-xylosylglucoside.

The composition may further include tectorigenin and tectoridine.

The inventors of the present invention increase the duration in the body when using tectorigenin, tectoridin, and tectorigenin 7-O-xylosylglucoside together, It was confirmed that the efficacy duration can be extended and the present invention has been completed.

The chemical formula of tectogeninin 7-O-xylosylglucoside of the present invention is C ₂₇ H ₃₀ O ₁₅ , and the molecular weight is 594.52, which can be represented by the following Chemical Formula 1.

[Formula 1]

The chemical formula of tectogenin of the present invention is C ₁₆ H ₁₂ O ₆ , and the molecular weight is 300.26, which can be represented by the following Chemical Formula 2.

[Formula 2]

The chemical formula of Tectolidine of the present invention is C ₂₂ H ₂₂ O ₁₁ , and the molecular weight is 462.40, which can be represented by the following Chemical Formula 3.

[Formula 3]

Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridine three compounds according to the present invention can be chemically synthesized by methods known in the art or commercially available materials.

In the present invention,'menopausal symptoms' is also referred to as'menopausal syndrome' or'menopausal symptoms'.

The composition of the present invention may have an excellent effect on the prevention, treatment and/or improvement of sweating, hot flashes, or osteoporosis among menopausal symptoms. Preferably, the composition of the present invention may have an excellent effect in preventing, improving and/or treating sweating, hot flashes and osteoporosis. Even more preferably, the composition of the present invention may have an excellent effect on sweating, prevention, improvement and/or treatment of hot flashes.

In the present invention,'facial flushing' is a typical symptom of vasomotor symptoms known to be experienced by 75% of menopausal women, and refers to the accompaniment of unpleasant heat and sweating of the whole body as the skin of the chest of the face and neck suddenly turns red. Menopausal vasomotor symptoms appear due to the narrowing of the thermoneutral zone in the hypothalamus due to hormonal changes in menopause, and even a slight increase in body temperature causes a feeling of heat.

In the present invention,'perspiration' is a phenomenon in which sweat is secreted from the sweat glands of the skin, and refers to a symptom of sweating as the heat rises abruptly.

In the present invention,'osteoporosis' refers to a condition in which bone strength is weakened and thus a fracture is likely to occur. Genetic factors, early menopause, drugs, or smoking are the causes. Therefore, it may be'menopausal osteoporosis' due to a decrease in hormone production due to menopause in women. Menopausal osteoporosis refers to osteoporosis symptoms caused by imbalance of osteoclasts involved in bone formation and osteoclasts involved in tissue destruction and absorption due to decreased hormone production in postmenopausal women.

In the present invention,'prevention' refers to all actions of suppressing or delaying a desired symptom by administering the composition of the present invention.

'Treatment' in the present invention means any action that improves or disappears a desired symptom or disease by administering the composition of the present invention.

In the present invention,'improvement' refers to all actions in which symptoms are improved or beneficially changed than before administration of the desired symptoms by administering the composition of the present invention.

The content of the compound or mixture included in the composition of the present invention may be included in an effective amount. The term'effective amount' refers to the amount of a compound or mixture that can inhibit or delay sweating, hot flashes or osteoporosis, or improve symptoms that have already appeared.

The content of the mixture contained in the composition may be included in various weights if it is possible to prevent, improve or treat sweating, hot flashes or osteoporosis. Specifically, for the entire composition, the sum of the three types of Tectorigen 7-O-Xylosylglucoside, Tectorigenin, and Tectoridine may be included in the amount of 10 to 500 mg based on the daily intake of menopausal women. For example, in the case of formulating the composition, when ingested once a day, the composition included in the formulation provided once, the tektorigenin 7-O-xylosylglucoside, tectorigenin, and tectolidine It may contain 10 to 500mg.

The composition may include tectorigenin, tectoridine, and tectorigenin 7-O-xylosylglucoside in a weight ratio of 1:0.5 to 20:0.5 to 20. Preferably in a weight ratio of 1: 0.8 to 15: 0.8 to 15, more preferably 1: 1.5 to 10: 1.5 to 10 may be included in a weight ratio.

When each active ingredient is included below the lower limit, the prevention, treatment or improvement efficacy of sweating, hot flashes or osteoporosis may not be exerted, and if it is included above the upper limit, there may be safety concerns.

The present invention can provide a cosmetic composition, a pharmaceutical composition, a food composition, including a composition comprising tectogenin 7-O-xylosylglucoside.

In another embodiment, the present invention provides a cosmetic composition, a pharmaceutical composition, and a food composition comprising a composition comprising a mixture of Tectorigenin, Tectoridine, and Tectorigenin 7-O-xylosylglucoside. Can.

The composition may be provided in the form of cosmetics, pharmaceuticals, food or quasi-drugs.

The pharmaceutical composition according to the present invention comprises a pharmaceutically effective amount of tectogeninin 7-O-xylosylglucoside; Or a mixture of tectorigenin, tectoridine, and tectorigen 7-O-xylosylglucoside alone, or may further include one or more pharmaceutically acceptable carriers, excipients, or diluents. The "pharmaceutically acceptable" is a non-toxic composition that is physiologically acceptable and does not inhibit the action of the active ingredient when administered to humans and does not normally cause allergic or similar reactions such as gastrointestinal disorders, dizziness, or the like. Says

Examples of the carrier, excipient, or diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose , Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, the pharmaceutical composition may further include a filler, anti-coagulant, lubricant, wetting agent, fragrance, emulsifier or preservative.

The "pharmaceutically effective amount" refers to an amount that exhibits a higher response than the negative control, and preferably refers to an amount sufficient to exhibit the effect of preventing, improving and/or treating menopausal disorder.

In addition, the pharmaceutical compositions of the present invention can be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. Formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders.

The route of administration of the pharmaceutical composition of the present invention is not limited thereto, but may be administered orally or parenterally. Parenteral routes of administration may include various routes, for example, transdermal, nasal, abdominal, muscle, subcutaneous or intravenous.

In addition, the pharmaceutical composition of the present invention may be administered in combination with a known compound having a preventive, ameliorating and/or therapeutic effect of menopausal disorder.

In another aspect, the present invention provides a food composition comprising any one of the above compositions.

The food composition of the present invention includes processed forms of all natural materials such as food, functional food, nutritional supplements, health feeds and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.

For example, as a health food, the composition of the present invention itself may be prepared in the form of tea, juice and drink to be consumed or granulated, encapsulated or powdered. In addition, the food composition of the present invention may further include other medicinal ingredients and/or additives that may be generally included in food compositions in the industry.

For example, the food composition according to the present invention may include thiamine (vitamin B1), riboflavin, ascorbic acid, niacin, and vitamin B6 as water-soluble vitamins, and myristic acid, palmitic acid, stearic acid, oleic acid as fatty acids, Linoleic acid, and the like, and may include glycolic acid and acetic acid as weak acid components, and threonine, valine, methionine, isoleucine, leucine, phenylalanine, tryptophan, and eight essential amino acids of lysine as amino acids, Aspartic acid, serine, glutamic acid, proline, glycine, alanine, cysteine, tyrosine, histidine, arginine, and the like.

In another aspect, the present invention provides a cosmetic composition comprising any one of the above compositions.

The ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions in addition to the active ingredients of the present invention, for example, conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances, And carriers.

Cosmetics according to the present invention can be prepared in any formulation conventionally prepared in the art. For example, it can be formulated as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray, etc. It is not limited to this.

More specifically, it can be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester.

When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspensions such as polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Sex cellulose, aluminum metahydroxide, bentonite, agar or trakant, etc. can be used.

When the formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide as a carrier component Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and in the case of a spray, additionally, chloro fluorohydrocarbon , Propane/butane or dimethyl ether.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide, etc. may be used as a carrier component. Can.

Since the composition according to the present invention has a rapid effect on the prevention, improvement and/or treatment of sweating, hot flashes and/or osteoporosis, it is useful for hormone replacement therapy (HRT) used to prevent or improve menopausal symptoms. Can be used.

In addition, the composition according to the present invention does not have cytotoxicity, as well as less side effects, and is safe to use as food, unlike conventional treatments for sweating, hot flashes, and osteoporosis, so sweating symptoms appearing after menopause in conventional women, hot flashes, It has high utilization as a treatment for osteoporosis.

The composition of the present invention may increase the duration of efficacy by increasing the duration in the body, including three mixtures of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin. Therefore, it is effective to increase facial flushing and sweating suppression time and reduce bone absorption.

1 is a graph showing the effect of improving vasomotor symptoms of three mixtures of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin according to an embodiment of the present invention.
Figure 2 is a graph showing the effect of improving the bone absorption of the three mixtures of Tectorigenin 7-O-xylosylglucoside, tectorigenin, tectoridin according to an embodiment of the present invention.

Hereinafter, examples and experimental examples will be described in detail to specifically describe the present invention. However, the examples and experimental examples according to the present invention may be modified in various other forms, and the scope of the present invention should not be interpreted as being limited to the examples and experimental examples described below. Examples and experimental examples of the present invention are provided to more fully describe the present invention to those skilled in the art.

[Sample preparation]

The following Tectorigenin 7-0-xylosylglucoside (Tectorigenin 7-O-xylosylglucoside) was purchased from Tokiwa, and Tectorigenin and Tectoridin were purchased from Sigma-Aldrich.

Example One. Tectorigenin 7-O- xylosylglucoside , tectorigenin , tectoridin Evaluation of estrogen receptor activity

To confirm the activity of the three estrogen receptors of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin, an ERE (estrogen response element) reporter assay was performed. The experimental method was carried out in the same manner as in Example 1, and tectorigenin, tectoridin, and Tectorigenin 7-O-xylosylglucoside were treated so that the sum of the three types was 10 ppm in the ratio of Table 1 below. Table 1 shows the experimental results using the measurement value of the negative control as a reference (1.0).

division ratio Estrogen receptor activity tectorigenin tectoridin Tectorigenin 7-O-xylosylglucoside Fold induction One 0 0 One 34 2 One One One 66 3 One 0.5 0.5 54 4 One 0.5 5 46 5 One 0.5 20 37 6 One 5 0.5 68 7 One 5 5 75 8 One 5 20 42 9 One 20 0.5 66 10 One 20 5 60 11 One 20 20 51

As shown in Table 1, when the three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin were treated together, it was confirmed that estrogen receptor activity was more excellent. In particular, it was found that the activity was different according to the treatment rate of three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin.

On the other hand, estrogen receptor activity was found to be remarkably low when the weight ratio of tectorigenin, tectoridine, and tectorigen 7-O-xylosylglucoside was 1: 0.5-20: 0.5-20.

Example 2. Effect of improving vasomotor symptoms

Vascular movement symptoms are known to be experienced by 75% of menopausal women, and hot flush is a typical symptom, and the skin of the face, neck, head, and chest suddenly turns red, accompanied by unpleasant heat. To confirm changes in vasomotor symptoms, changes in skin temperature can be evaluated as indicators, and in animal experiments, the skin surface temperature of the rat tail can be measured. (Health Functional Food Functional Evaluation Guide,'Can Help Women's Health in Menopause', Food and Drug Safety Evaluation Institute)

Female Sprague-Dawley rats aged 11 to 12 weeks were used to perform sham operation in 10 groups in group 1 and sham operation in 50 groups in group 2 to 6 (n=10 per group) (ovariectomy, OVX). Groups were divided into groups as shown in Table 2, and after 1 week of surgery, the rats were orally administered the drug daily for 4 weeks at a rate of 0.01 ml per g. As a positive control group, 17β-estradiol (E2) was administered, and in the test group, three types of tectorigenin, tectoridin, and Tectorigenin 7-O-xylosylglucoside were mixed at a 1:5:5 ratio. After 4 weeks of administration, the temperature was measured 2 cm from the start of the tail using an infrared thermometer, and the measurement results are shown in FIG. 1.

group Operation Dosage sample District 1 Sham drinking water District 2 OVX drinking water District 3 OVX 17β-estradiol (E2), 0.5mg/kg/day Group 4 OVX T3*, 5mg/kg/day District 5 OVX T3*, 10mg/kg/day District 6 OVX Tectorigenin, 10mg/kg/day District 7 OVX Tectoridin, 10mg/kg/day District 8 OVX Tectorigenin 7-O-xylosylglucoside, 10mg/kg/day

*T3: tectorigenin, tectoridin, Tectorigenin 7-O-xylosylglucoside 3 kinds 1:5:5 mixed

As shown in Table 3 and Figure 1, as a result of administering a mixture of three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, tectoridin, it was confirmed that the tail temperature rise due to estrogen deficiency is suppressed.

group District 1 District 2 District 3 Group 4 District 5 District 6 District 7 District 8 Tail skin temperature (℃) 27.5 28.8 27.4 27.9 27.5 28.6 28.7 28.0

Specifically, as can be seen in Table 3, among three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin, tail temperature when Tectorigenin 7-O-xylosylglucoside was administered compared to Tectorigenin and Tectolidin The rise was most suppressed. On the other hand, it was confirmed that the increase in tail skin temperature was most suppressed in groups 4 and 5 in which three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin were administered together.

Example 3. Bone resorption Improvement effect

Serum was collected after oral administration of samples in the same rats as in Example 3 for 8 weeks for the measurement of CTX (C-terminal telopeptide of type I collagen), an index related to bone resorption. CTX concentration in serum was measured according to the method provided by the manufacturer using the Rat C-telopeptide of type I collagen ELISA Kit (MyBioSource), and the results are shown in FIG. 3.

As shown in Figure 2 and Table 4, in the case of the group treated with three mixtures of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin, it was confirmed that the CTX concentration was significantly lower than that of the OVX group, and bone absorption was reduced. Can be inferred.

group District 1 District 2 District 3 Group 4 District 5 District 6 District 7 District 8 CTX (ng/ml) 42.3 78.2 52.6 60.7 49.1 71.5 70.4 58.4

Specifically, as can be seen in Table 4, among the three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin, compared to Tectorigenin and Tectolidin, bone of bone when Tectorigenin 7-O-xylosylglucoside was administered Absorption was most suppressed. On the other hand, it was confirmed that the absorption of bone was most inhibited in the 5 groups administered with three types of Tectorigenin 7-O-xylosylglucoside, tectorigenin, and tectoridin.

Claims (9)

Tectorigenin 7-O-xylyl glucoside comprising a composition for preventing or improving hot flashes. According to claim 1, wherein the composition is a composition for preventing or improving hot flashes, characterized in that it further comprises Tectorigenin and Tectolidine. A composition for preventing or ameliorating osteoporosis comprising tectorigenin 7-O-xylosylglucoside. [4] The composition for preventing or improving osteoporosis according to claim 3, wherein the composition further comprises tectorigenin and tectolidine. A composition for preventing or improving sweating comprising tectogenin 7-O-xylosylglucoside. The composition for preventing or improving sweating according to claim 5, wherein the composition further comprises tectorigenin and tectolidine. Tectorigenin 7-O-xylyl glucoside comprising a pharmaceutical composition for the treatment of hot flashes. Tectorigenin 7-O-xylylglucoside. Tectorigenin 7-O-xylyl glucoside, pharmaceutical composition for the treatment of osteoporosis.

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