Composition for preventing, alleviating, improving or treating female hormone dysregulation disorders or symptoms, containing green tea extract with altered component content

Abstract

To provide a composition for preventing, alleviating, improving or treating female hormone regulation disorder or symptoms, which contains a green tea extract with contents of ingredients changed.SOLUTION: The present invention relates to a composition for preventing, alleviating, improving or treating female hormone regulation disorder or symptoms, which contains a green tea extract containing 4-15 wt % of (-)-gallocatechin gallate (GCG) and 4-15 wt % of (-)-epigallocatechin gallate (EGCG) based on the total weight of the extract, as an active ingredient. The extract and the composition according to an exemplary embodiment of the present invention have no side effect and are environment-friendly and safe because they are derived from a natural plant. In addition, they can exhibit superior effect of preventing, alleviating, improving or treating female hormone regulation disorder or symptoms.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing, alleviating, improving or treating female hormone dysregulation disorders or symptoms, which comprises a green tea extract with an altered component content. [Background technology]

[0002] Premenstrual syndrome (PMS) refers to the physical and mental symptoms experienced by women during their fertile period. PMS is known to occur during the latter half of the luteal phase, approximately one week before menstruation, when the body's progesterone levels decrease, leading to a decrease in endorphin levels. While the intensity and duration of PMS pain vary from person to person, 10-15% of women experience physical and mental pain severe enough to interfere with their daily lives. Severe menstrual pain can also cause severe abdominal pain, along with nausea, vomiting, diarrhea, headaches, and dizziness. Pain-related stress and depression can also occur, potentially interfering with social activities such as work and school. Therefore, preventing, alleviating, and treating PMS is crucial for women's normal activities and lifestyles.

[0003] The International Health Organization (WHO) also classifies premenstrual syndrome and menstrual pain as diseases requiring treatment under the disease classification code N94 (N943: premenstrual syndrome, N944: primary dysmenorrhea, N945: secondary dysmenorrhea). The number of patients receiving medical treatment for menstrual pain is increasing year by year, resulting in rising social medical costs. According to a survey conducted by the National Health Insurance in Korea, the number of patients receiving treatment for menstrual pain (N94) increased by 47.93% in 2011, and the resulting health insurance medical costs increased by 78.85% over the five-year period (2007-2011). Therefore, there is a growing need for effective and safe treatments for premenstrual syndrome and menstrual pain to reduce these social losses.

[0004] Treatments for the relief and treatment of premenstrual syndrome and menstrual cramps include symptomatic treatments such as keeping the lower abdomen warm, avoiding cold foods, light exercise, and taking warm showers to promote blood circulation. Medical treatments include the administration of prostaglandin inhibitors, estrogen therapy (which suppresses ovulation and maintains anovulation), progesterone therapy, testosterone therapy, and tocolytics. The most common treatment involves the administration of painkillers (typically aspirin-based drugs) that inhibit prostaglandin synthesis. However, their use is limited for those with aspirin-based drug allergies or digestive disorders. While these drugs are effective in temporarily reducing pain, they do not provide relief from the emotional anxiety and inconvenience experienced by patients with premenstrual syndrome. Furthermore, excessive dependence on painkillers or long-term use can lead to side effects such as gastrointestinal or vascular disorders, making long-term use undesirable. Therefore, there is a need for the development of an agent for preventing, alleviating and treating premenstrual symptoms and menstrual pain that is highly effective and safe and can be administered for a long period of time.

[0005] In addition, women generally enter menopause around the age of 50 due to a rapid decline in ovarian function. As menopause continues, the secretion of the female hormone estrogen also decreases, resulting in an increased risk of developing menopausal symptoms such as osteoporosis, hyperlipidemia, facial hot flashes, breast cancer, and depression. Therefore, active research is being conducted on functional health foods and pharmaceuticals that can effectively regulate blood estrogen levels, which are important for the treatment and prevention of menopausal symptoms, as well as biomarkers related to menopausal women's diseases.

[0006] A study of menopausal women has shown that applying estrogen to the skin significantly improves elasticity, dryness, wrinkles, etc., making estrogen a powerful anti-aging substance that improves skin aging. However, these hormone ingredients have limitations in that they cannot be used as ingredients in products such as cosmetics, so there is a need to discover effective ingredients that can replace estrogen to improve the causes of menopausal skin aging.

[0007] Furthermore, hormone replacement therapies that have already been developed are known to have various side effects. For example, when estrogen is administered as hormone replacement therapy, it is known to carry risks such as endometritis, breast cancer, gallbladder disease, breast pain, mood changes, high blood pressure or thrombophlebitis, and weight gain. Therefore, it is not recommended for all menopausal women to undergo hormone replacement therapy, and some menopausal women are hesitant to try it or give up midway through.

[0008] Therefore, there is a pressing need to develop natural ingredients that can replace hormones to alleviate menopausal symptoms in women. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Korean Patent Publication No. 10-2019-0139472 [Patent Document 2] Korean Patent Publication No. 10-2019-0003247 Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention aims to provide a composition derived from natural plants that is highly effective, safe, and has no side effects, and that is highly effective in preventing, alleviating, improving, or treating female hormone dysregulation diseases or symptoms. [Means for solving the problem]

[0011] To achieve the above object, as one embodiment, the present invention provides a composition for preventing, alleviating, improving or treating female hormone dysregulation diseases or symptoms, comprising a green tea extract containing 4 to 15 wt % (-)-gallocatechin gallate (GCG) and 4 to 15 wt % (-)-epigallocatechin gallate (EGCG) based on the total weight of the extract as active ingredients. [Effects of the Invention]

[0012] The extract and composition according to one embodiment of the present invention are safe, derived from natural plants, have no side effects, and are environmentally friendly, and therefore can exhibit excellent efficacy in preventing, alleviating, improving, or treating female hormone dysregulation diseases or symptoms. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 shows a chromatogram for the notified green tea extract of Production Example 1 (Sample 1). [Figure 2] FIG. 1 shows a chromatogram for a high-temperature treated green tea extract (sample 2) according to one aspect of the present invention. [Figure 3] FIG. 1 shows the results of evaluating the efficacy of Test Example 1 in improving premenstrual symptoms based on the change in the mean total score of a self-questionnaire. [Figure 4] FIG. 1 shows the results of evaluation of efficacy in improving premenstrual symptoms in Test Example 1 based on the change in the average mood score in a self-administered questionnaire. [Figure 5] FIG. 1 shows the evaluation results of efficacy in improving menopausal symptoms in Test Example 2. [Figure 6] FIG. 1 shows the evaluation results of efficacy in activating estrogen receptors in Test Example 3. [Figure 7] FIG. 1 shows the results of evaluation of the inhibitory effect on the growth of MCF-7 breast cancer cell line in Test Example 4. DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention will be described in detail below.

[0015] As used herein, the term "premenstrual syndrome" refers to a syndrome exhibiting emotional, behavioral, and physical symptoms that recur before menstruation. Specifically, the symptoms of premenstrual syndrome include physical symptoms such as abdominal distension, lower back pain, headache, breast pain, and swelling of the limbs; emotional symptoms such as mood swings, depression, anxiety, discomfort, aggression, irritability, confusion, and chaos; and mental symptoms such as sleep disorders, appetite changes, decreased concentration, decreased interest, and social withdrawal. These symptoms are characterized by gradually worsening after ovulation, reaching their peak about one week before the onset of menstruation, and disappearing within a few days after menstruation.

[0016] In this specification, "menopausal symptoms" include physical and mental symptoms such as weight gain, arthritis, muscle pain, hyperlipidemia, facial flushing, breast cancer, liver cell destruction, joint pain, fatigue, excitement, headache, night sweats, insomnia, irritability, anxiety, dizziness, decreased concentration, memory loss, and depression, as well as skin aging symptoms such as decreased skin elasticity, skin wrinkle formation, decreased skin luster, and dry skin.

[0017] As used herein, the term "green tea extract" refers to an extract from the tea plant (Camellia sinensis), an evergreen tree belonging to the Tea family, regardless of the extraction method, extraction solvent, extracted components, or extract form. It also includes an extract from tea leaves inoculated with Bacillus subtilis spp. and fermented, and a fraction obtained by fractionating the extract with a specific solvent. The tea may include one or more parts selected from the group consisting of leaves, flowers, stems, fruits, roots, stems, and root cores of the tea plant, preferably leaves. The extract may also be in the form of powder. The extraction or fractionation may be performed using water, an organic solvent, or a mixture thereof. Examples of organic solvents that may be used include, but are not limited to, alcohol, isopropanol, acetone, hexane, ethyl acetate, carbon dioxide, or a mixture of two or more thereof. The extraction or fractionation may be performed at room temperature or with heating under conditions that do not destroy or minimize the destruction of the active ingredients of green tea. The alcohol may be a C1 to C5 lower alcohol. The number of times or method of extraction or fractionation is not particularly limited, and methods such as cold maceration extraction, ultrasonic extraction, reflux cooling extraction, and hot water extraction may be used. Preferably, the green tea extract of the present invention is obtained by extracting or fractionating the active ingredient by cold maceration or heating, filtering, and then concentrating the filtrate under reduced pressure.

[0018] As used herein, the term "epicatechin" includes epigallocatechin (EGC), (-)-epicatechin (EC), (-)-epigallocatechin gallate (EGCG), and epicatechin 3-O-gallate (ECG).

[0019] As used herein, the term "epicatechin epimer" includes gallocatechin (GC), catechin (C), (-)-gallocatechin gallate (GCG), and catechin gallate (CG).

[0020] In one aspect, the present invention may relate to a composition for preventing, alleviating, ameliorating, or treating female hormone dysregulation diseases or symptoms, comprising, as active ingredients, a green tea extract containing 4 to 15 wt % of (-)-gallocatechin gallate (GCG) and 4 to 15 wt % of (-)-epigallocatechin gallate (EGCG), based on the total weight of the extract.

[0021] In another aspect, the present invention may relate to a method for preventing, alleviating, ameliorating, or treating a female hormone dysregulation disease or symptom, the method comprising administering to a subject in need thereof an effective amount of a green tea extract containing 4 to 15 wt % (-)-gallocatechin gallate (GCG) and 4 to 15 wt % (-)-epigallocatechin gallate (EGCG), based on the total weight of the extract.

[0022] In still another aspect, the present invention may relate to use of a green tea extract containing 4 to 15 wt % of (-)-gallocatechin gallate (GCG) and 4 to 15 wt % of (-)-epigallocatechin gallate (EGCG), based on the total weight of the extract, for producing a composition for preventing, alleviating, ameliorating, or treating female hormone dysregulation diseases or symptoms.

[0023] In one embodiment, the female hormone dysregulation disease or condition may be at least one selected from the group consisting of premenstrual syndrome, female menopausal symptoms, hypoestrogenism, and breast cancer.

[0024] In one embodiment, the GCG may be present in an amount of 4% by weight or more, 5% by weight or more, 5.3% by weight or more, 5.59% by weight or more, 5.7% by weight or more, 6% by weight or more, 7% by weight or more, 8% by weight or more, 9% by weight or more, 10% by weight or more, 11% by weight or more, 12% by weight or more, 13% by weight or more, or 14% by weight or more, based on the total weight of the extract. In another embodiment, the GCG may be present in an amount of 15% by weight or less, 14% by weight or less, 13% by weight or less, 12% by weight or less, 11% by weight or less, 10% by weight or less, 9% by weight or less, 8% by weight or less, 7% by weight or less, 6% by weight or less, 5.7% by weight or less, 5.59% by weight or less, 5.3% by weight or less, or 5% by weight or less, based on the total weight of the extract. When the GCG is present in the above content ranges, excellent efficacy in preventing, alleviating, improving, or treating female hormone dysregulation diseases or symptoms can be demonstrated.

[0025] In one embodiment, the EGCG may be at least 4 wt%, at least 5 wt%, at least 5.2 wt%, at least 5.27 wt%, at least 5.5 wt%, at least 6 wt%, at least 7 wt%, at least 8 wt%, at least 9 wt%, at least 10 wt%, at least 11 wt%, at least 12 wt%, at least 13 wt%, or at least 14 wt%, based on the total weight of the extract. In other embodiments, the EGCG may be at most 15 wt%, at most 14 wt%, at most 13 wt%, at most 12 wt%, at most 11 wt%, at most 10 wt%, at most 9 wt%, at most 8 wt%, at most 7 wt%, at most 6 wt%, at most 5.5 wt%, at most 5.27 wt%, at most 5.2 wt%, or at most 5 wt%, based on the total weight of the extract.

[0026] The green tea extract according to one aspect of the present invention contains a significantly reduced amount of EGCG compared to existing green tea extracts, but contains GCG at a level similar to that of EGCG, and can therefore exhibit excellent efficacy in preventing, alleviating, improving, or treating female hormone dysregulation diseases or symptoms.

[0027] In one embodiment, the total content of GCG and EGCG in the extract may be 30 wt% or less, based on the total weight of the extract. In one aspect, the total content of GCG and EGCG may be 30 wt% or less, 25 wt% or less, 20 wt% or less, 18 wt% or less, 16 wt% or less, 15 wt% or less, 14 wt% or less, 12 wt% or less, 10.5 wt% or less, 10 wt% or less, or 9 wt% or less, based on the total weight of the extract. In another aspect, the total content of GCG and EGCG may be 8 wt% or more, 9 wt% or more, 10 wt% or more, 10.5 wt% or more, 12 wt% or more, 13 wt% or more, 14 wt% or more, 16 wt% or more, 18 wt% or more, 20 wt% or more, or 25 wt% or more, based on the total weight of the extract.

[0028] In one embodiment, the epicatechin content of the extract may be 20 wt% or less, based on the total weight of the extract. In one aspect, the epicatechin content may be 20 wt% or less, 18 wt% or less, 16 wt% or less, 15 wt% or less, 14 wt% or less, 12 wt% or less, 11 wt% or less, or 10 wt% or less, based on the total weight of the extract. In another aspect, the epicatechin content may be 9 wt% or more, 10 wt% or more, 11 wt% or more, 12 wt% or more, 13 wt% or more, 14 wt% or more, 16 wt% or more, or 18 wt% or more, based on the total weight of the extract.

[0029] In one embodiment, the total content of eight catechins in the extract, i.e., the total content of EGCG, (-)-epigallocatechin (EGC), (-)-epicatechin (EC), epicatechin 3-O-gallate (ECG), GCG, gallocatechin (GC), catechin (C), and catechin gallate (CG), in the extract may be in the range of 19 to 30 wt% based on the total weight of the extract. In one aspect, the total content of the eight catechins may be 19% by weight or more, 21% by weight or more, 23% by weight or more, 24% by weight or more, 24.5% by weight or more, 25% by weight or more, 26% by weight or more, 27% by weight or more, 28% by weight or more, or 29% by weight or more, based on the total weight of the extract. In another aspect, the total content of the eight catechins may be 30% by weight or less, 29% by weight or less, 28% by weight or less, 27% by weight or less, 26% by weight or less, 25% by weight or less, 24.5% by weight or less, 24% by weight or less, 23% by weight or less, or 21% by weight or less, based on the total weight of the extract.

[0030] In one embodiment, the weight ratio of GCG:EGCG in the extract may be in the range of 1:0.5 to 2. In one aspect, the weight ratio of GCG:EGCG in the extract may be 1:0.5, 1:0.8, 1:1, 1:1.2, 1:1.5, 1:1.8, or 1:2.

[0031] When the weight ratio of GCG:EGCG is within the above range, it can exhibit safe and excellent efficacy in preventing, alleviating, improving or treating female hormone dysregulation diseases or symptoms without any side effects.

[0032] In one embodiment, the extract may be extracted one or more times with water and / or a C1-C4 alcohol. In one aspect, the alcohol may be ethanol. In another aspect, the alcohol may be 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, or 70% or more ethanol. In still another aspect, the alcohol may be 70% or less, 60% or less, 50% or less, 40% or less, or 30% or less ethanol.

[0033] In one embodiment, the content of the green tea extract in the composition for alleviating or ameliorating female hormone dysregulation disorders or symptoms may be in the range of 1% to 100% by weight, based on the total weight of the composition. In one aspect, the content of the extract in the composition may be 1% by weight or more, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, 70% by weight or more, 80% by weight or more, or 90% by weight or more. In another aspect, the content of the extract in the composition may be 100% by weight or less, 90% by weight or less, 80% by weight or less, 70% by weight or less, 60% by weight or less, 50% by weight or less, 40% by weight or less, 30% by weight or less, or 20% by weight or less.

[0034] In one embodiment, the dosage of the active ingredient may range from 5 mg / kg / day to 1000 mg / kg / day, and in one aspect, the dosage may be 5 mg / kg / day or more, 100 mg / kg / day or more, 200 mg / kg / day or more, 300 mg / kg / day or more, 400 mg / kg / day or more, 500 mg / kg / day or more, 600 mg / kg / day or more, 700 mg / kg / day or more, 800 mg / kg / day or more, or 900 mg / kg / day or more. In other aspects, the dosage may be 1000 mg / kg / day or less, 900 mg / kg / day or less, 800 mg / kg / day or less, 700 mg / kg / day or less, 600 mg / kg / day or less, 500 mg / kg / day or less, 400 mg / kg / day or less, 300 mg / kg / day or less, 200 mg / kg / day or less, 100 mg / kg / day or less, 50 mg / kg / day or less, or 10 mg / kg / day or less.

[0035] In another embodiment, the extract can increase the activation of estrogen beta receptor (ER-β), thereby alleviating or improving female hormone dysregulation disorders or symptoms, such as premenstrual syndrome or menopausal symptoms.

[0036] In one embodiment, the composition for alleviating or ameliorating a female hormone dysregulation disease or symptom may be a food, pharmaceutical, or cosmetic composition. More specifically, when the female hormone dysregulation disease or symptom is a skin disease or symptom, for example, a menopausal skin symptom, the composition for alleviating or ameliorating a female hormone dysregulation disease or symptom may be a cosmetic composition.

[0037] The dosage form of the food composition is not particularly limited, and may be, for example, tablets, granules, pills, powders, liquids such as drinks, caramels, gels, bars, tea bags, etc. In addition to the active ingredient, a person skilled in the art may easily select and blend ingredients commonly used in the art according to the dosage form or intended use of the food composition, and when used in combination with other ingredients, a synergistic effect may be produced. The food may also be a functional health food.

[0038] The composition may be administered in a variety of ways, such as by simple ingestion, drinking, injection, spraying or squeezing.

[0039] In the food composition according to one aspect of the present invention, the determination of the dosage of the active ingredient is within the level of a person of ordinary skill in the art, and may vary depending on various factors such as the age, health condition, and complications of the subject to be administered.

[0040] The food composition according to one aspect of the present invention may be, for example, various foods such as chewing gum, caramel products, candies, ice cream, and snacks; beverage products such as refreshing drinks, mineral water, and alcoholic drinks; and functional health food products containing vitamins and minerals.

[0041] In addition to the above, food compositions according to one aspect of the present invention may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, colorants and enhancers (e.g., for cheese, chocolate), pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like. Additionally, food compositions according to one aspect of the present invention may contain natural fruit juices and fruit pulp for producing fruit juice beverages and vegetable beverages. These ingredients may be used independently or in combination. The proportion of these additives is not critical, but typically ranges from 0 to about 60 parts by weight per 100 parts by weight of a composition according to one aspect of the present invention.

[0042] The pharmaceutical composition according to one aspect of the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc. Dosage forms for oral administration may be, but are not limited to, tablets, pills, soft and hard capsules, granules, powders, fine granules, liquids, emulsions, or pellets. Dosage forms for parenteral administration may be, but are not limited to, solutions, suspensions, emulsions, gels, injections, drip infusions, suppositories, patches, or sprays. The dosage forms can be easily prepared according to conventional methods in the art and may further include surfactants, excipients, hydrating agents, emulsifiers, suspending agents, salts or buffers for osmotic pressure adjustment, colorants, spices, stabilizers, antiseptics, preservatives, or other commonly used adjuvants.

[0043] The composition according to one aspect of the present invention may include a pharmaceutically acceptable salt, which may be formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; or from an acid such as acetic acid, propionic acid, hexanoic acid, cyclopentenepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, or the like. or (2) salts formed when an acidic proton present in the parent compound is replaced by another acid.

[0044] The dosage or administration amount of the pharmaceutical composition according to one aspect of the present invention may vary depending on the age, sex, weight, pathological condition and its severity, route of administration, and the judgment of the prescriber. Determining the dosage of the active ingredient based on such factors is within the level of one of ordinary skill in the art.

[0045] The cosmetic composition according to one aspect of the present invention may contain a cosmetically or dermatologically acceptable medium or base. This may be provided in any dosage form suitable for topical application, such as a solution, gel, solid, a paste-free product, an emulsion obtained by dispersing an oily phase in an aqueous phase, a suspension, a microemulsion, microcapsules, microgranules, or ionic (liposome) and non-ionic vesicular dispersions, or in the form of a cream, skin lotion, powder, ointment, spray, or concealer stick. These compositions may be prepared by conventional methods in the art. The cosmetic composition may also be used in the form of an aerosol composition further containing a propellant compressed in the form of a foam.

[0046] The cosmetic composition is not particularly limited in its formulation and may be appropriately selected depending on the intended purpose. For example, the cosmetic composition may be prepared in the form of a skin lotion, skin softener, skin toner, lotion, milk lotion, moisturizing lotion, nourishing lotion, massage cream, nourishing cream, moisturizing cream, hand cream, foundation, essence, nourishing essence, pack, soap, cleansing foam, cleansing lotion, cleansing cream, cleansing water, powder, body lotion, body cream, body oil, body cleanser, body essence, etc.

[0047] When the dosage form of the present invention is a paste, cream, or gel, the carrier component may be animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide, or the like.

[0048] When the dosage form of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component, and particularly when it is a spray, it may further contain a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0049] When the dosage form of the present invention is a solution or emulsion, a solvent, solvating agent, or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, aliphatic esters of glycerol, polyethylene glycol, or fatty acid esters of sorbitan.

[0050] When the dosage form of the present invention is a suspension, the carrier component may be a liquid diluent such as water, ethanol, or propylene glycol; a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, or polyoxyethylene sorbitan ester; microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tragacanth.

[0051] When the dosage form of the present invention is a surfactant-containing cleanser, the carrier component may be a fatty alcohol sulfate, a fatty alcohol ether sulfate, a sulfosuccinate monoester, isethionic acid, an imidazolium derivative, methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkylamidobetaine, a fatty alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a lanolin derivative, or an ethoxylated glycerol fatty acid ester.

[0052] In addition to the green tea extract, the cosmetic composition may further contain functional additives and ingredients commonly contained in cosmetic compositions. The functional additives may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymeric peptides, polymeric polysaccharides, sphingolipids, and seaweed extracts.

[0053] The composition may further contain, in addition to the functional additives, ingredients commonly found in cosmetic compositions, such as oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, UV absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, blood circulation enhancers, cooling agents, antiperspirants, purified water, etc.

[0054] The present invention can provide the following embodiment as an example.

[0055] The first embodiment can provide a composition for preventing, alleviating, improving, or treating female hormone dysregulation diseases or symptoms, comprising a green tea extract containing 4 to 15 wt % (-)-gallocatechin gallate (GCG) and 4 to 15 wt % (-)-epigallocatechin gallate (EGCG) based on the total weight of the extract as active ingredients.

[0056] A second embodiment can provide the composition of the first embodiment, wherein the female hormone dysregulation disease or symptom is at least one selected from premenstrual syndrome, menopausal symptoms, and estrogen hypotension.

[0057] A third embodiment can provide a composition according to one or more of the first and second embodiments, wherein the weight ratio of GCG:EGCG in the extract is in the range of 1:0.5-2.

[0058] A fourth embodiment can provide a composition according to one or more of the first to third embodiments, wherein the extract is one or more of a water extract, a methanol extract, an ethanol extract, a propanol extract, and a butanol extract.

[0059] The fifth embodiment can provide a composition according to one or more of the first to fourth embodiments, wherein the content of the extract in the composition is in the range of 1 wt % to 100 wt % relative to the total weight of the composition.

[0060] A sixth embodiment can provide a composition according to one or more of the first to fifth embodiments, wherein the dosage of the active ingredient is in the range of 5 mg / kg / day to 1000 mg / kg / day.

[0061] The seventh embodiment can provide a composition in one or more of the first to sixth embodiments, wherein the composition is a food, pharmaceutical, or cosmetic composition.

[0062] The present invention will be described in more detail below with reference to Preparation Examples, Examples, and Test Examples. Note that these Preparation Examples, Examples, and Test Examples are presented merely to facilitate understanding of the present invention, and the scope of the present invention is not limited to these Examples and Test Examples. Furthermore, modifications, substitutions, and insertions commonly known in the art may be made, and such modifications, substitutions, and insertions are also included within the scope of the present invention.

[0063] [Production Example 1] Production of Notification-type Green Tea Extract and High-Temperature-Processed Green Tea Extract 100g of green tea (Camellia sinensis, Osulloc Farm, Jeju Island) was added to 1000ml of 50% ethanol and stirred under reflux at 60°C for 1 hour. The temperature of the sample was lowered to room temperature, and the filtered solution was distilled under reduced pressure to obtain 23g of a dark brown powder of a general notification type green tea extract (GT-LE-35CAT, sample 1) (yield 23%).

[0064] On the other hand, to prepare high-temperature processed green tea extract, 100g of green tea (Camellia sinensis, Osulloc Farm, Jeju Island) was added with 1000ml of 50% ethanol and stirred under reflux at 60°C for 1 hour. After concentrating, the extract was heated under steam at 1.5kgf / cm. 2 The mixture was stirred at RT for 1 to 7 hours. The temperature was then lowered to room temperature, and the insoluble material was filtered and concentrated under reduced pressure to obtain 10 g of high-temperature processed green tea extract. The high-temperature processed green tea extract obtained at each stirring time (1 to 7 hours) was measured for changes in the content of eight catechins using the equipment shown in Table 1 below. It was confirmed that the conversion of EGCG to GCG due to heat was at its highest at 5 hours, and that the amount of the eight catechins had not decreased any further. The 10 g of high-temperature processed green tea extract (HTP-GTE) obtained at this time was designated Sample 2.

[0065] The conditions and results of analyzing the compositions of the two extracts obtained are shown in Table 1 (composition analysis conditions for Samples 1 and 2), Table 2 (composition analysis results for Sample 1), and Table 3 (composition analysis results for Sample 2), respectively. The chromatograms for the two extracts are shown in Figures 1 (Sample 1) and 2 (Sample 2). That is, Sample 2 was confirmed to have a different composition from existing green tea extracts. Specifically, Sample 2 contained significantly lower amounts of EGCG (5.27 wt%), EGC (3.53 wt%), and total catechins (24.41 wt%) than Sample 1. However, it was confirmed that four epicatechin epimers, components not found in Sample 1, were also produced.

[0066] [Table 1]

[0067] [Table 2]

[0068] [Table 3]

[0069] In Tables 2 and 3, GC represents gallocatechin, EGC represents epigallocatechin, C represents catechin, EC represents (-) epicatechin, GCG represents gallocatechin gallate, EGCG represents epigallocatechin gallate, CG represents catechin gallate, and ECG represents epicatechin 3-O-gallate.

[0070] The units in Tables 2 and 3 are all the weight percentages of the substance relative to the total weight of the green tea extract (samples 1 and 2).

[0071] [Production Example 2] Production of high-temperature processed green tea extracts with different GCG:EGCG ratios Sample 2 of Production Example 1 was further subjected to a heat stirring treatment (steam 1.5 kgf / cm 2 After adding the mixture, the temperature was lowered to room temperature, the insoluble matter was filtered off, and the mixture was concentrated under reduced pressure. GCG was then added to the mixture to obtain 10 g of Sample 3 (GCG:EGCG=1:0.33) having the composition shown in Table 4 below. 2 After 2 hours, the temperature was lowered to room temperature, the insoluble matter was filtered, and the mixture was concentrated under reduced pressure to obtain 10 g of Sample 4 (GCG:EGCG=1:3) having the composition shown in Table 5 below.

[0072] [Table 4]

[0073] [Table 5]

[0074] In Tables 4 and 5, GC represents gallocatechin, EGC represents epigallocatechin, C represents catechin, EC represents (-) epicatechin, GCG represents gallocatechin gallate, EGCG represents epigallocatechin gallate, CG represents catechin gallate, and ECG represents epicatechin 3-O-gallate.

[0075] The units in Tables 4 and 5 are all weight percentages of the substance relative to the total weight of the green tea extract (samples 3 and 4).

[0076] [Production Example 3] Production of theanine 10 kg of green tea leaves (Camellia sinensis, Osulloc Farm, Jeju Island) were extracted with hot water and then eluted with 1N sodium hydroxide (NaOH) using a cation exchange resin. The eluted solution was purified with activated carbon and eluted with 15% (v / v) ethanol (EtOH). It was then concentrated using an RO (reverse osmosis) membrane, purified by column chromatography, and crystallized to produce 24.8 g of L-theanine.

[0077] [Test Example 1] Evaluation of efficacy in improving premenstrual syndrome To evaluate the efficacy of the notified green tea extract, high-temperature-treated green tea extract, and theanine in improving premenstrual symptoms, 500 mg tablets containing 225 mg of Sample 1 (notified green tea extract), 225 mg of Sample 2 (high-temperature-treated green tea extract), 225 mg of Sample 3, and 225 mg of Sample 4 from Preparation Examples 1 and 2, and 12.5 mg of theanine from Preparation Example 3 were manufactured using a tabletop single-punch tablet press (ERWEKA, Germany). A control drug was also manufactured using the same method, except that 225 mg of maltodextrin (Target Corporation) was used.

[0078] According to the diagnostic criteria for premenstrual syndrome (Table 6), those with five symptoms, including one physical symptom, were considered to be in the premenstrual syndrome group. Of 88 women in their 20s to 50s of childbearing age, 60 were selected as study subjects. The 60 women were randomly divided into six groups, each with 10 participants: Sample 1 (publicly recognized green tea extract group), Sample 2 (high-temperature processed green tea extract group), Sample 3 (group), Sample 4 (group), theanine group, and control group (control drug group). Each group completed a premenstrual syndrome self-assessment questionnaire (Table 7) before their first menstrual period, and then took the appropriate tablets twice a day (two tablets per dose) for approximately four weeks until the end of their next menstrual period. That is, each group took 900 mg of the notified green tea extract (Sample 1), high-temperature processed green tea extract (Sample 2), Sample 3, and Sample 4 per day, and 50 mg of theanine per day. After the intake was completed, the subjects were asked to complete the self-questionnaire they had completed before their period again, and the average changes in total score and mood score were confirmed. The results are shown in Figure 3 (change in total score) and Figure 4 (change in mood score).

[0079] [Table 6]

[0080] [Table 7]

[0081] As shown in FIG. 3, it was confirmed that the subjects who ingested the high-temperature processed green tea extract of Sample 2 according to one embodiment of the present invention had a significantly reduced average total score compared to the subjects who ingested other notified green tea extracts, Samples 3 and 4, and the subjects who ingested theanine, an amino acid found in large amounts in green tea.

[0082] Furthermore, as shown in FIG. 4, regarding the mental symptoms (numbers 21 to 26) among the items in the questionnaire in Table 7, it was confirmed that the average score of the mental symptoms was significantly reduced in the subjects who ingested the high-temperature processed green tea extract of Sample 2 according to one embodiment of the present invention, compared to the subjects who ingested other notified green tea extracts, Sample 3, Sample 4, and the subjects who ingested theanine, an amino acid found in large amounts in green tea.

[0083] From the above results, it was confirmed that the high-temperature processed green tea extract of Sample 2 according to one embodiment of the present invention is very effective in alleviating or improving the physical and mental symptoms of premenstrual syndrome.

[0084] In particular, among samples 2 to 4, which are high-temperature processed green tea extracts, sample 2, which has a GCG:EGCG weight ratio of approximately 1:0.9, was confirmed to show a significant and excellent effect in alleviating or improving the physical and mental symptoms of premenstrual syndrome compared to samples 3 and 4, which have GCG:EGCG weight ratios of approximately 1:0.3 and 1:3, respectively.

[0085] [Test Example 2] Evaluation of efficacy in improving menopausal symptoms To evaluate the efficacy of the notified green tea extract, high-temperature-treated green tea extract, and theanine in improving premenstrual symptoms, 500 mg tablets containing 225 mg of Sample 1 (notified green tea extract), 225 mg of Sample 2 (high-temperature-treated green tea extract), 225 mg of Sample 3, and 225 mg of Sample 4 from Preparation Examples 1 and 2, and 12.5 mg of theanine from Preparation Example 3 were manufactured using a tabletop single-punch tablet press (ERWEKA, Germany). A control drug was also manufactured using the same method, except that 225 mg of maltodextrin (Target Corporation) was used.

[0086] The study subjects were 60 women with an average age of 50 years, who were pre- and post-menopausal and had a total score of 5 or higher on the menopausal symptom assessment scale (Table 8) below. These 60 women were randomly divided into six groups (10 women each). The study was conducted in the following groups: a group taking the designated green tea extract (Sample 1), a group taking high-temperature processed green tea extract (Sample 2), a group taking Sample 3, a group taking Sample 4, a group taking theanine, and a control group (control drug). The 60 women completed the menopausal symptom assessment scale (Table 8) below before taking each tablet, and then took two tablets twice daily for four weeks. Specifically, each group received 900 mg of designated green tea extract (Sample 1), high-temperature processed green tea extract (Sample 2), Sample 3, or Sample 4 daily, and 50 mg of theanine daily. After the end of the intake period, the menopausal symptom assessment scale was completed again to determine the average change in total score. The results are shown in Figure 5.

[0087] [Table 8]

[0088] As shown in FIG. 5, it was confirmed that the subjects who ingested the high-temperature processed green tea extract of Sample 2 according to one embodiment of the present invention had a significantly reduced average total score compared to the subjects who ingested other notified green tea extracts, Samples 3 and 4, and the subjects who ingested theanine, an amino acid found in large amounts in green tea.

[0089] These results confirmed that the high-temperature processed green tea extract of Sample 2 according to one embodiment of the present invention is highly effective in alleviating or improving the physical and mental symptoms of menopause.

[0090] Furthermore, among the high-temperature processed green tea extracts Samples 2 to 4, Sample 2, which has a GCG:EGCG weight ratio of approximately 1:0.9, was confirmed to exhibit significant and superior effects in alleviating or improving the physical and mental symptoms of menopause compared to Samples 3 and 4, which have GCG:EGCG weight ratios of approximately 1:0.3 and 1:3, respectively.

[0091] [Test Example 3] Evaluation of estrogen receptor activation efficacy To evaluate the efficacy of the notified green tea extract, high-temperature-treated green tea extract, and theanine in activating estrogen α and β receptors (ERα / β) at various GCG:EGCG weight ratios, Sample 1 (notified green tea extract), Sample 2 (high-temperature-treated green tea extract), Sample 3, Sample 4, and theanine from Preparation Example 3 were treated at concentrations of 20 μg / ml, 20 μg / ml, and 1 μg / ml, respectively, in a human ERα / β reporter assay panel (IB00421-48P, Indigo Bioscience) for 24 hours, and the level of increased activity of estrogen receptors ERα and ERβ was analyzed. 100 pM 17β-estradiol, which was included in the assay panel, was used as a positive control.

[0092] Specifically, the cells included in the human ERα / β reporter assay panel overexpress ERα and ERβ, respectively, and contain the ERE-luc reporter gene. When the activity of the estrogen receptor increases upon treatment with the test substance, ERα and ERβ bind to ERE and induce the expression of luciferase. The activity of ERα and ERβ can then be measured by measuring the level of luminescence emitted from the cells. The results are shown in Figure 6.

[0093] 6, when the activation level of estrogen receptors ERα and ERβ was analyzed by luciferase activity measurement, the notified green tea extract of Sample 1, Samples 3 and 4, and theanine treatment did not show any receptor activation effect, whereas the high-temperature-treated green tea extract of Sample 2 according to one embodiment of the present invention showed the effect of increasing the activity of estrogen receptors ERα and ERβ. This result indicates that the high-temperature-treated green tea extract according to one embodiment of the present invention can be effective in alleviating or improving premenstrual syndrome or menopausal symptoms by increasing the activity of estrogen receptors ERα and ERβ.

[0094] In particular, among samples 2 to 4, which are high-temperature processed green tea extracts, sample 2, which has a GCG:EGCG weight ratio of approximately 1:0.9, showed a significant effect of increasing the activity of estrogen receptors ERα and ERβ compared to samples 3 and 4, which have GCG:EGCG weight ratios of approximately 1:0.3 and 1:3, respectively, while samples 3 and 4 were confirmed to be at the same level as the remaining general, notified green tea extracts and theanine.

[0095] Furthermore, the results of Figure 6 confirmed that while 17b-estradiol, the positive control, increased the activity of both estrogen receptors ERα and ERβ to similar levels, the high-temperature-treated green tea extract of Sample 2 according to one embodiment of the present invention increased ERβ activity to a much greater extent than ERα. Activation of ERα increases breast cancer cell growth and cell division, leading to a higher incidence of breast cancer. However, since ERβ inhibits ERα activity and thus cancer cell growth, a higher increase in ERβ activity compared to ERα is expected to significantly reduce the risk of developing breast cancer, a known side effect of estrogen replacement therapy. Therefore, the following Test Example 4 was conducted to determine whether the high-temperature-treated green tea extract according to the present invention exhibits the side effect of promoting breast cancer cell growth.

[0096] [Test Example 4] Evaluation of growth inhibitory effect on MCF-7 breast cancer cell line MCF-7 cells (breast cancer cell line) obtained from the Korea Cell Line Bank were treated for 48 hours with the official green tea extract, high-temperature processed green tea extract, Sample 3, and Sample 4 (Preparation Example 1) at 20 μg / ml each, theanine (Preparation Example 3) at 1 μg / ml, and 17β-estradiol (100 pM) at 100 pM each, and then the cell number was measured using a cell counting device (Countess, Thermo Fisher Scientific). The results are shown in Figure 7.

[0097] As shown in Figure 7, 17b-estradiol, which was used as a positive control for estrogen receptor activation in Test Example 3, not only exhibited excellent ERβ activation efficacy but also significantly activated ERα to a similar extent, thereby significantly promoting the growth of MCF-7 breast cancer cells and causing significant side effects such as breast cancer development. In contrast, the high-temperature-treated green tea extract of Sample 2 according to one embodiment of the present invention did not exhibit such side effects and instead exhibited an effect of inhibiting the growth of MCF-7 cells.

[0098] Furthermore, in the case of Samples 3 and 4, which are high-temperature processed green tea extracts and have a GCG:EGCG weight ratio of approximately 1:0.3 and 1:3, respectively, it was confirmed that, as in Test Example 3, there was no significant effect on the activity of estrogen receptors ERα and ERβ, and therefore no significant effect on the growth of MCF-7 cells.

[0099] These results demonstrate that the high-temperature processed green tea extract of sample 2 according to one embodiment of the present invention exhibits excellent estrogen receptor activation efficacy without the side effects of existing estrogen replacement therapy, and may even be effective in preventing or treating breast cancer.

[0100] [Dosage Form Example 1] Soft capsule A soft capsule filling solution was prepared by mixing 150 mg of Sample 2 from Example 1 with 440 mg of lactose, 430 mg of corn starch, and 2 mg of magnesium stearate. Separately from the filling solution, a soft capsule sheet was prepared using 66 parts by weight of gelatin, 24 parts by weight of glycerin, and 10 parts by weight of sorbitol liquid, and the filling solution was filled into the soft capsules to prepare soft capsules.

[0101] [Dosage form example 2] Tablets 150 mg of Sample 2 from Example 1 was prepared, mixed with 15 mg of vitamin E, 15 mg of vitamin C, 250 mg of galactooligosaccharide, 60 mg of lactose, and 140 mg of maltose, and then granulated using a fluidized bed dryer. 8 mg of sugar ester was added to the granulated mixture, and the resulting composition was compressed into tablets by a conventional method.

[0102] [Dosage Form Example 3] Drink 80 mg of Sample 2 according to Example 1 was prepared, mixed with 9 mg of vitamin E, 9 mg of vitamin C, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide, and then 400 ml of purified water was added and the mixture was bottled. After filling into the bottle, the mixture was sterilized at 30°C for 4 to 5 seconds to produce a drinkable preparation.

[0103] [Dosage Form Example 4] Granules 150 mg of sample 2 according to Example 1 was prepared, mixed with 9 mg of vitamin E, 9 mg of vitamin C, 250 mg of anhydrous crystalline glucose, and 550 mg of starch, and then formed into granules using a fluidized bed granulator. The granules were then packed into sachets to produce the granules.

[0104] [Dosage Form Example 5] Health Food A health food product was manufactured by preparing 150 mg of Sample 2 according to Example 1 and combining it with a vitamin mixture (vitamin A acetate 70 μg, vitamin E 1.0 mg, vitamin B1 0.13 mg, vitamin B2 0.15 mg, vitamin B6 0.5 mg, vitamin B12 0.2 μg, vitamin C 10 mg, biotin 10 μg, nicotinamide 1.7 mg, and folic acid 50 μg) and an inorganic mixture (ferrous sulfate 1.75 mg, zinc oxide 0.82 mg, magnesium carbonate 25.3 mg, monopotassium phosphate 15 mg, dibasic calcium phosphate 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg).

[0105] [Dosage form example 6] Health drink 50 mg of Sample 2 according to Example 1 was prepared, and 900 mL of a health drink was prepared by adding 1000 mg of citric acid, 100 g of oligosaccharides, 2 g of plum concentrate, 1 g of taurine, and the remaining amount of purified water.

[0106] Although specific examples of the present specification have been described in detail above, it will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the present specification. Therefore, the true scope of the present specification is defined by the appended claims and their equivalents.

Claims

1. The present invention relates to a green tea extract containing, as active ingredients, 4 to 15% by weight of (-)-gallocatechin gallate (GCG) and 4 to 15% by weight of (-)-epigallocatechin gallate (EGCG), based on the total weight of the extract; the weight ratio of GCG:EGCG in the extract is in the range of 1:0.5-2; A composition for preventing, alleviating, improving or treating female hormone dysregulation diseases or symptoms.

2. The composition according to claim 1, wherein the female hormone dysregulation disease or condition is at least one selected from the group consisting of premenstrual syndrome, menopausal symptoms, hypoestrogenism, and breast cancer.

3. The composition according to claim 1 or 2, wherein the extract is any one or more of a water extract, a methanol extract, an ethanol extract, a propanol extract, and a butanol extract.

4. The composition according to any one of claims 1 to 3, wherein the content of the extract in the composition is in the range of 1% by weight to 100% by weight, based on the total weight of the composition.

5. The composition according to any one of claims 1 to 4, wherein the dosage of the active ingredient ranges from 5 mg / kg / day to 1000 mg / kg / day.

6. The composition according to any one of claims 1 to 5, wherein the composition is a food, pharmaceutical, or cosmetic composition.

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