WO2020241958A1 - Composition pour prévenir ou traiter les symptomes de la ménopause chez la femme, comprenant un concentré de cordyceps militaris en tant que principe actif - Google Patents
Composition pour prévenir ou traiter les symptomes de la ménopause chez la femme, comprenant un concentré de cordyceps militaris en tant que principe actif Download PDFInfo
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- WO2020241958A1 WO2020241958A1 PCT/KR2019/006992 KR2019006992W WO2020241958A1 WO 2020241958 A1 WO2020241958 A1 WO 2020241958A1 KR 2019006992 W KR2019006992 W KR 2019006992W WO 2020241958 A1 WO2020241958 A1 WO 2020241958A1
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- Prior art keywords
- cordyceps militaris
- concentrate
- menopausal symptoms
- preventing
- pharmaceutical composition
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/302—Foods, ingredients or supplements having a functional effect on health having a modulating effect on age
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/208—Fungi extracts
Definitions
- the present invention relates to a composition for preventing or treating women's menopausal symptoms, comprising a concentrate of Cordyceps militaris as an active ingredient.
- Women's menopause occurs in their 40s to 50s, and is due to a decrease in the secretion of estrogen, that is, female hormones due to aging of the ovaries, and appears over 2-10 years before and after menopause.
- menopausal syndrome has a profound effect on the physical and mental health and quality of life of middle-aged women. Therefore, there is an absolutely need for a way to treat it.
- hormone replacement therapy in order to treat women's menopausal symptoms, hormone replacement therapy, nonsteroidal preparations, and drug therapy for osteoporosis have been developed, and among them, the most effective method known so far is hormone replacement therapy.
- “Hormone replacement therapy” refers to a treatment in which female hormones are administered to alleviate symptoms caused by a lack of female hormones in menopausal women. When female hormones are administered alone, endometrial proliferation can occur, so progesterone is usually administered in combination.
- menopausal women have higher waist circumference, systolic blood pressure, pulse pressure, total cholesterol, low-density lipoprotein cholesterol, and triglycerides than premenopausal women.
- menopausal women are a time when many metabolic changes appear due to changes in female hormones, and in particular, menopausal women at this time are at increased risk of being exposed to obesity due to increased body fat.
- Obesity in middle-aged women is a time that is highly associated with the onset of adult diseases that increase mortality such as coronary artery, heart disease, stroke, diabetes, and high blood pressure.
- menopausal women are also at high risk of being exposed to obesity, which is highly related to the onset of various adult diseases, and efforts to improve not only female menopausal symptoms but also accompanying obesity are needed.
- the inventors of the present invention are researching the prevention or treatment of female menopausal symptoms, while cordyceps sinensis concentrate is capable of preventing or treating female menopausal symptoms caused by changes in female hormones, and obesity induced by female menopause. By showing the effect of improving, it was confirmed that it can be usefully used in the prevention and treatment of female menopausal symptoms and obesity induced by female menopause, and the present invention was completed.
- Patent Document 0001 Korean Patent Application Publication No. 10-2017-0055081
- Patent Document 0002 Korean Patent Application Publication No. 10-2009-0088205
- Another object of the present invention is to provide a food composition for preventing or improving female menopausal symptoms comprising a cordyceps militaris concentrate as an active ingredient.
- Another object of the present invention is to provide a method for preventing, improving or treating female menopausal symptoms, comprising administering a therapeutically effective amount of Cordyceps militaris concentrate to a subject in need of treatment.
- Another object of the present invention is to provide a use of a cordyceps militaris concentrate for the treatment of female menopausal symptoms.
- the present inventors recognized the need for research on the prevention or treatment of female menopausal symptoms, and attempted to achieve the purpose of research on natural substances capable of preventing or treating female menopausal symptoms.
- cordycepin-containing cordyceps improves female menopausal symptoms and obesity induced by female menopause while searching for components with high treatment for female menopausal symptoms.
- the invention was completed.
- Cordyceps militaris concentrate according to the present invention was confirmed to be able to prevent or treat female menopausal symptoms due to female hormone reduction due to the female hormone estrogen activity.
- weight gain inhibition in female menopausal induction animal models, weight gain inhibition, abdominal fat
- Cordyceps militaris concentrate has an excellent effect of inhibiting obesity induced by female menopause.
- Cordyceps sinensis Cordyceps militaris
- Pharmaceutical composition for preventing or treating women's menopausal symptoms containing concentrate as an active ingredient
- the present invention provides a pharmaceutical composition for preventing or treating female menopausal symptoms comprising a cordyceps militaris concentrate as an active ingredient.
- hormone replacement therapy in which estrogen is administered as a treatment for women's menopause is known to be the most effective method, but long-term use of drugs can cause endometrial cancer, breast cancer, high blood pressure, thrombosis, and diabetic stones, and bleeding and ovarian excess. There is a problem that it cannot be taken without a doctor's prescription due to side effects such as irritation.
- the pharmaceutical composition of the present invention contains the natural substance "cordyceps sinensis concentrate" as an active ingredient, so the side effects of estrogen injection It was confirmed that the female hormone estrogen activity is capable of preventing or treating female menopausal symptoms caused by female hormone reduction, while suppressing weight gain, reducing abdominal fat, and improving blood lipids in female menopausal induction animal models.
- cordyceps militaris is a type of filamentous fungus, which is parasitic to insects, kills the host insect, and produces fruiting bodies such as clubs or stripes.
- the fruiting body consists of two parts of a head and a stem, and the head is bulging into a ball shape, a cylinder shape with pointed ends, a spatula shape, etc., and forms several ascaris on the surface or under the epidermis.
- Cordyceps militaris is used as a medicinal mushroom in oriental medicine, and as a medicinal mushroom, it is distributed in Korea, Japan, China, and Nepal.
- Cordyceps militaris along with ginseng and deer antlers, is known as one of the three major remedy in China, and is known as an elixir of longevity and tonic. It is reported to be. In addition, Cordyceps militaris concentrate has been reported to have anti-inflammatory and anti-cancer activities such as lymphoma, leukemia, and bladder cancer, as well as immunity control and strengthening effects.
- ⁇ concentrate'' refers to a liquid composition that is diluted with a drinkable liquid to provide a beverage or is added to a food product before consumption, and if a substance obtained by separating the ingredients contained in the raw material from a natural product , Regardless of the method of concentration or the kind of ingredients, all can be included.
- ⁇ active ingredient'' includes a substance or group of substances that is expected to directly or indirectly express the efficacy effect of the composition through its inherent pharmacological action (including herbal medicines for which the pharmacologically active ingredient, etc. is not known. ) Means to include the main component.
- female menopausal symptoms refers to all symptoms that appear in the body due to ovarian function decline due to aging and female hormone decline.
- the female menopausal symptoms are mainly, blood lipid disorder, bone density decrease, body fat increase, abdominal obesity, facial flushing, sweating, skin dryness, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, urinary pain, urination, concentration disorder, Short-term memory impairment, anxiety, nervousness, memory loss, muscle pain, joint pain, and osteoporosis may appear.
- women's menopausal symptoms mean weight gain, body fat increase, and abdominal fat increase associated with obesity.
- prevention refers to all actions of suppressing or delaying female menopausal symptoms by administration of the pharmaceutical composition according to the present invention.
- treatment refers to any action in which symptoms appearing during female menopause are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.
- the Cordyceps militaris extract may be prepared by extraction in water, an anhydrous lower alcohol having 1 to 4 carbon atoms, or a hydrated lower alcohol solvent having 1 to 4 carbon atoms.
- anhydrous lower alcohol having 1 to 4 carbon atoms is a lower alcohol that does not contain water, and includes, for example, methanol, ethanol, propanol, butanol, and isobutanol, but is not limited thereto.
- ⁇ hydrous lower alcohol having 1 to 4 carbon atoms'' is a lower alcohol mixed with water, for example, methanol, ethanol, propanol, butanol, isobutanol, and a mixed solvent of water, and specifically, may be a mixed solvent of water and ethanol.
- the mixing ratio of water and ethanol may be 30% (v/v) to 70% (v/v) ethanol aqueous solution obtained by mixing water and ethanol in a volume ratio of 7:3 to 3:7, and specifically It may be a 50% (v/v) aqueous ethanol solution in which water and ethanol are mixed in a volume ratio of 5:5.
- the cordyceps militaris concentrate contains cordycepin, and the content of cordycepin is 0.02 to 10% by weight based on the total weight of the cordyceps militaris concentrate. It may be, specifically 0.1 to 5% by weight, or may be contained in a high content of 0.2 to 2% by weight.
- the female menopausal symptoms may be due to a decrease in female hormones.
- ⁇ female hormone'' is a hormone secreted by the ovary, and may mean estrogen, which is follicular hormone (FSH), and progesteron, which is a progesterone (LH), and specifically estrogen. it means.
- FSH follicular hormone
- LH progesterone
- the female menopausal symptoms include blood lipid disorder, bone density decrease, body fat increase, abdominal obesity, hot flashes, sweating, skin dryness, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, It may be urinary pain, urination, concentration disorder, short-term memory impairment, anxiety, nervousness, memory loss, muscle pain, joint pain, osteoporosis, or a combination thereof.
- the cordyceps militaris concentrate is a first extraction step of obtaining a first extract by mixing and extracting (S1) Cordyceps militaris and a first extraction solvent, and the first It can be obtained by a second extraction step of mixing and extracting the Cordyceps militaris solids subjected to the tea extraction step and a second extraction solvent to obtain a second extract.
- the first extraction solvent refers to an extraction solvent that is mixed with the dried Cordyceps militaris after removing foreign substances by washing the Cordyceps militaris , removing moisture through drying, and drying the cordyceps militaris .
- the first extraction solvent may be water, an anhydrous lower alcohol having 1 to 4 carbon atoms, or a hydrated lower alcohol solvent having 1 to 4 carbon atoms, and can be applied in the same manner as described above.
- the first extraction step is to mix the dried cordyceps militaris and the first extraction solvent, 5L to 20L of the first extraction solvent per kg of Cordyceps militaris may be mixed, specifically Cordyceps militaris ( Cordyceps militaris ) 20 kg of 50L to 400L of the first extraction solvent may be mixed, specifically, Cordyceps militaris 20 kg of 100L to 300L of the first extraction solvent may be mixed, and limited thereto no.
- the first extraction step may be extracted for 24 to 120 hours in a state in which Cordyceps militaris and the first extraction solvent are mixed, and specifically, may be extracted for 48 to 96 hours, and is limited thereto. It is not.
- the first extraction liquid means a liquid solution separated after the first extraction step.
- the second extraction solvent means an extraction solvent mixed with the solid Cordyceps militaris solid that has been subjected to the first extraction step.
- the second extraction solvent may be water, an anhydrous lower alcohol having 1 to 4 carbon atoms, or a hydrated lower alcohol solvent having 1 to 4 carbon atoms, and can be applied in the same manner as described above.
- the second extraction step is to mix the solid cordyceps militaris solid material and the second extraction solvent that has been subjected to the first extraction step, and 1L to 4L of the second extraction solvent per kg of Cordyceps militaris is It may be mixed, specifically Cordyceps militaris 20 kg of the second extraction solvent of 20L to 80L may be mixed, but is not limited thereto.
- the second extraction step may be extracted for 1 to 10 hours in a state in which the Cordyceps militaris solid and the second extraction solvent are mixed, and specifically for 2 to 6 hours, limited thereto. It does not become.
- the second extract refers to a liquid solution separated after a second extraction step.
- the method of extracting the concentrate of Cordyceps militaris of the composition according to the present invention may use hot water extraction, immersion extraction, ultrasonic extraction, shaking extraction, Soxhelt extraction, or reflux extraction, specifically mixing water and ethanol It may be shaking extraction using 50% ethanol, but is not limited thereto.
- the number of extractions may be 1 to 5 times, specifically 1 to 3 times, but is not limited thereto.
- the extraction time may be 1 hour to 120 hours, specifically, extraction may be performed for 3 hours to 96 hours, but is not limited thereto.
- the extraction temperature may be 20°C to 40°C, specifically 25°C to 35°C, but is not limited thereto.
- the amount of the extraction solvent is 1 to 20 times the dry weight of Cordyceps militaris .
- the cordyceps militaris concentrate has a content of 0.1% to 95% by weight based on the total weight of the composition comprising the cordyceps militaris concentrate.
- Cordyceps militaris according to the present invention may be obtained by further comprising the following steps, but is not limited thereto.
- the cordyceps militaris concentrate is (S2) the first extract and the second extract using a diatomaceous earth filter aid after the first extraction step and the second extraction step. It can be obtained by a filtration step of filtration under reduced pressure to obtain a filtrate, and (S3) a concentration step of obtaining a concentrate of Cordyceps militaris by concentrating the filtrate under reduced pressure.
- the solution may be filtered or centrifuged according to a conventional method in the art to obtain a filtrate or a supernatant.
- the concentration is preferably concentrated under reduced pressure, and the concentration under reduced pressure is preferably a vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto.
- Cordyceps sinensis concentrate is extracted in liquid or powder form by this concentration.
- the drying is preferably vacuum drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.
- the pharmaceutical composition of the present invention contains a concentrate of Cordyceps militaris as an active ingredient, and may further include a pharmaceutically acceptable carrier, and powders, granules, tablets, capsules, suspensions, according to conventional methods, It can be formulated in the form of oral dosage forms such as emulsions, syrups, aerosols, external preparations, and sterile injectable solutions.
- the term "pharmaceutically acceptable” refers to a composition that is physiologically acceptable and does not usually cause allergic reactions such as gastrointestinal disorders and dizziness or similar reactions when administered to humans.
- the term "pharmaceutically acceptable carrier” typically includes a liquid or non-liquid basis of a pharmaceutical composition.
- the carrier typically comprises pyrogen-free water; Isotonic saline or buffer (aqueous) solutions, such as phosphate, citric acid, etc. buffer solutions.
- the injection buffer can be on a hypertonic, isotonic or hypotonic basis for a specific reference media, i.e. the buffer can have a high, the same or a low salt content for a specific reference media, preferably osmotic pressure or other concentration effects. Such concentrations of the aforementioned salts, which do not induce cell damage by, can be used.
- the reference medium is blood, lymph, cytoplasmic liquid, or other body fluid, or a body fluid that can be used as a reference medium in the "ex vivo" method, for example as a general buffer or liquid. It is liquid.
- a general buffer or liquid Such general buffers or liquids are known to the skilled person.
- the pharmaceutically acceptable carriers are those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like, but are not limited thereto.
- composition of the present invention may contain diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and other pharmaceutically acceptable additives.
- the pharmaceutical composition of the present invention may be prepared in the form of a liquid, suspension, powder, granule, tablet, capsule, pill, or extract.
- composition of the present invention can be administered orally or parenterally (eg, application or intravenous, subcutaneous, intraperitoneal injection).
- oral administration is a method of injecting a drug for improving pathological symptoms by mouth
- parenteral administration refers to subcutaneous, intramuscular, and It refers to a method of intraperitoneal administration using an intravenous or tube.
- Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills, and the like.
- Liquid preparations for oral administration include suspensions, liquid contents, emulsions, syrups, aerosols, etc.
- various excipients such as humectants, sweeteners, fragrances, preservatives, etc. May be included.
- Formulations for parenteral administration include aqueous solutions, liquids, non-aqueous solutions, suspensions, emulsions, eye drops, ointments, syrups, suppositories, aerosols, and other external preparations and sterile injections, each sterilized according to a conventional method. It may be used in combination, and preferably, a pharmaceutical composition of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, eye ointment, eye drop, pasta or cataplasma may be prepared and used. However, it is not limited thereto. Compositions for topical administration may be anhydrous or aqueous, depending on the clinical prescription.
- non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
- injectable ester such as ethyl oleate
- a base for suppositories witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used.
- the pharmaceutically acceptable additive according to the present invention may include 0.1 to 99.9 parts by weight, specifically 0.1 to 50 parts by weight, with respect to the composition, but is not limited thereto.
- the preferred dosage of the composition of the present invention depends on the degree of absorption of the active ingredient in the body, the age, sex, and degree of obesity of the patient, but may be appropriately selected by those skilled in the art. However, for a desirable effect, in the case of oral administration, the composition of the present invention per 1 kg of body weight per day is generally administered to an adult at 0.0001 to 40 mg/kg per day, preferably 0.001 to 20 mg/kg. It is good.
- Administration may be administered once a day, or may be divided several times.
- the above dosage does not in any way limit the scope of the present invention.
- composition for preventing or treating female menopausal symptoms of the present invention may contain one or more active ingredients showing the same or similar function in addition to the concentrate of Cordyceps militaris .
- Cordyceps sinensis Cordyceps militaris
- Food composition for preventing or improving women's menopausal symptoms containing concentrate as an active ingredient
- the present invention provides a food composition for preventing or improving women's menopausal symptoms comprising a cordyceps militaris concentrate as an active ingredient.
- the food composition for preventing or improving female menopausal symptoms according to the present invention exhibits excellent effects in preventing or treating female menopausal symptoms through weight loss inhibitory effect and estrogen receptor activation. In addition, it shows an excellent effect even through oral administration, so the medication compliance is very high.
- the term "improvement” refers to the act of improving all bad conditions that appear in female menopause by administering or ingesting a pharmaceutical composition containing the concentrate of Cordyceps militaris according to the present invention.
- the food composition of the present invention can be used as a health functional food.
- the term “health functional food” refers to a food manufactured and processed using raw materials or ingredients having functions useful for the human body according to the Health Functional Food Act No.6727, and in this specification, the term “ “Functionality useful for the human body” means ingestion for the purpose of obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body.
- the cordyceps militaris concentrate of the present invention When using the cordyceps militaris concentrate of the present invention as a health functional food or health functional beverage additive, the cordyceps militaris concentrate is added as it is or used with a conventional food additive, and can be appropriately used according to a conventional method. have. Unless otherwise specified, the suitability as a food additive shall be determined according to the standards and standards for the relevant item in accordance with the General Regulations of Food Additives Code and General Test Methods approved by the Food and Drug Administration.
- Food Additives Code include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as dark pigments, licorice extract, crystalline cellulose, high color pigments, and guar gum, L -Mixed preparations such as sodium glutamate preparations, noodle-added alkali preparations, preservatives preparations, and tar coloring preparations.
- the mixed amount of the cordyceps militaris concentrate may be appropriately determined according to the purpose of use (prevention, health or improvement, therapeutic treatment). In the case of long-term intake for the purpose of health and hygiene or for the purpose of health control, the Cordyceps militaris concentrate has no problem in terms of safety, and thus can be taken for a long time.
- the food composition of the present invention may be variously used for foods and beverages, and there is no particular limitation on the type.
- foods to which the Cordyceps militaris concentrate can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, It can be used for beverages, teas, drinks, alcoholic beverages and vitamin complexes, and can be used in the form of powders, granules, tablets, capsules, pills or beverages. In addition to those described above, it can be in any food form.
- the liquid component added in addition to the Cordyceps militaris concentrate is not limited thereto, but may contain various flavoring agents or natural carbohydrates as an additional component, such as a conventional beverage.
- natural carbohydrates described above are monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.) and polysaccharides (e.g., common sugars such as dextrin, cyclodextrin, etc.), and xylitol. , Sorbitol, and sugar alcohols such as erythritol.
- natural sweeteners [taumarin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and synthetic sweeteners (eg, saccharin, aspartame, etc.) may be used as sweetening agents.
- synthetic sweeteners eg, saccharin, aspartame, etc.
- the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and enhancing agents (cheese, chocolate, etc.), pectic acid and salts thereof, Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like may be contained.
- the food composition of the present invention may contain pulp for the production of fruit and vegetable beverages. These components may be used alone or in combination, and the proportion of these additives is generally selected from 0.001 to 50 parts by weight per total weight of the composition.
- the product containing the concentrate of Cordyceps militaris of the present invention may be a powder, granule, tablet, capsule, syrup, or beverage.
- the present invention provides a method for preventing, improving or treating female menopausal symptoms by administering a therapeutically effective amount of Cordyceps militaris concentrate to a subject in need of treatment.
- the term "subject in need of treatment” refers to a mammal, including humans, and the term “administration” refers to providing a predetermined substance to a patient by any suitable method.
- the term ⁇ therapeutically effective amount'' refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in an animal or human considered by a researcher, veterinarian, doctor or other clinician, which is a disease to be treated. Or an amount that induces symptomatic relief of the disorder. It is obvious to those skilled in the art that the therapeutically effective dosage and frequency of administration of the active ingredient of the present invention will vary depending on the desired effect.
- the present invention provides the use of Cordyceps militaris concentrate for the treatment of female menopausal symptoms.
- cordyceps sinensis Cordyceps militaris
- the present invention provides a use of the cordyceps militaris concentrate to prepare a pharmaceutical formulation for the treatment of female menopausal symptoms.
- the use of the present invention can be used to prepare a pharmaceutical formulation for the treatment of female menopausal symptoms by preventing, ameliorating or treating female menopausal symptoms.
- Cordyceps militaris concentrate of the present invention has proven estrogen activity, and reduced weight gain, diet increase, body fat and abdominal fat induced by female menopause in a female menopausal induction animal model, thereby reducing female menopausal symptoms and female menopausal symptoms. It has an excellent effect in preventing or improving accompanying obesity.
- 1 is a graph confirming estrogen-like activity by confirming the cell proliferation by treating the concentrate of Cordyceps militaris according to an embodiment of the present invention to MCF-7 cells proliferating by estrogen stimulation.
- Figure 2 is a graph confirming the estrogen-like activity by confirming the cell proliferation by treating the Queens One Tab (Queens One Tab) to the proliferating MCF-7 cells by estrogen stimulation.
- Figure 3 is a diagram showing a Western blot result of measuring the expression of ER ⁇ and phosphorylated ER ⁇ (pER ⁇ ) for confirming the estrogen receptor response of Cordyceps militaris concentrate according to an embodiment of the present invention.
- Figure 4 is a graph showing the weight loss effect of the cordyceps militaris concentrate in an animal model for inducing menopausal symptoms according to an embodiment of the present invention.
- FIG. 5 is a graph showing changes in dietary intake of cordyceps militaris concentrate in a female menopausal symptom induction animal model according to an embodiment of the present invention.
- FIG. 6 is a graph showing the change in fat content (%) of the concentrate of Cordyceps militaris in the female menopausal symptom induction animal model according to an embodiment of the present invention.
- FIG. 7 is a picture taken by dual energy X-ray absorptiometry of the whole body of a cordyceps militaris concentrate in a female menopausal symptom induction animal model according to an embodiment of the present invention. It means low-, medium-, and high-density fat in the order of yellow and red.
- Figure 8 is a graph showing the change in the serum lipid composition of the cordyceps militaris concentrate in the female menopausal symptom induction animal model according to an embodiment of the present invention.
- the numerical range includes the numerical values defined in the above range. All maximum numerical limits given throughout this specification include all lower numerical limits as if the lower numerical limits were expressly written. All minimum numerical limits given throughout this specification are inclusive of all higher numerical limits as if the higher numerical limits were expressly written. All numerical limits given throughout this specification will include all better numerical ranges within the wider numerical range, as the narrower numerical limits were expressly written.
- Cordyceps sinensis used in the examples of the present invention was purchased from Mustech Co., Ltd. in Korea, and the reagents and solvents mentioned below were purchased from Sigma-Aldrich unless otherwise noted.
- Example 1 Cordyceps sinensis ( Cordyceps militaris ) Preparation of concentrate
- Cordyceps militaris 20 kg was added to the extraction tank. After adding 200L of 50% (v/v) aqueous ethanol solution as the first extraction solvent to the extraction tank, the first extraction was performed at room temperature for 72 hours.
- the first extract and the second extract were mixed and filtered under reduced pressure using a diatomaceous earth filter aid to obtain a filtrate.
- the filtrate was concentrated under reduced pressure under the condition of 30 mmHg to 65 brix or more to obtain a Cordyceps militaris concentrate.
- Cordyceps militaris concentrate of Example 1 was added to a 10 mL flask and dissolved in 5 mL distilled water while stirring with a stirrer. Thereafter, 5 mL ethanol was added, shaken, and then shaken for 20 minutes with ultrasonic waves. After cooling, about 1 mL was taken, transferred to a 1.5 mL EP tube, and centrifuged at 13,000 RPM for 5 minutes, and the supernatant was used as a sample solution. After dissolving 20.0 mg cordycepine in 50% ethanol, it was diluted several times in a manner of diagnosing to 100 mL to prepare a standard solution for calibration in a concentration range of 5 to 50 ⁇ g/mL. The content of cordycepine was measured using liquid chromatography in 10 ul of the test solution and standard solution according to the conditions in Table 1 below.
- cordycepine content a calibration curve was obtained from the concentration and peak area of the sample solution and the standard solution, and the peak area of cordicepine was substituted to calculate the cordycepine concentration.
- the formula for calculating the cordycepine content (%) is as follows.
- the sugar content of the concentrate of Cordyceps militaris was evaluated by putting an appropriate amount into a sugar content meter (refractometer).
- MCF-7 Mese Cancer Foundation-7 cells having proliferative activity for estrogen, a female hormone, were used.
- MCF-7 cells were cultured in Phenol red-free RPMI1640 medium (Gibco) containing 10% dextran-coated charcoal-stripped FBS. After dispensing MCF-7 cells in a 6 well plate at a concentration of 3 ⁇ 10 5 cells/well, incubate at 37°C in 5% CO 2 conditions, 24
- the concentrate of Cordyceps militaris according to Example 1 was treated with 5, 10, and 25 ⁇ g/mL.
- Queen's Expedition Kerungjin Pharmaceutical Co., Ltd.
- the cell proliferation rate (unit: %) was measured by measuring the number of cells after each sample was treated with respect to the number of cells in the untreated state.
- MCF-7 cells were subjected to a temperature of 37°C and 5 in RPMI1640 medium (Gibco) containing 10% fetalbovine serum (FBS, Gibco), penicillin G (100 ⁇ g/mL), and streptomycin sulfate (100 ⁇ g/mL).
- % CO 2 was cultivated under humid conditions supplied, and cordyceps sinensis concentrate was treated.
- the extracted protein was quantified using the BCA (Bicinchoninic acid, Sigma) quantification method, and then the total protein was quantified and then separated using SDS-PAGE (Sodium dodecyl sulfate polyacrylamide gel). ), the antibody was reacted.
- the primary antibody used in the experiment was ER ⁇ (1:2000, cell signaling), phospho-ER ⁇ (ser118) (1:2000, cell signaling), and GAPDH (1:5000, cell signaling), and the secondary antibody Horseradish peroxidase-attached anti-mouse antibody (1:3000, cell signaling) and anti-rabbit antibody (1:3000, cell signaling) were used.
- the expression levels of ER ⁇ , pER ⁇ and GAPDH were measured using SuperSignal West Femto Maximum Sensitivity Substrate (Thermo Scientific) and fusion solo (VILBER LOURMAT).
- the animals used in the experiment were rat 7-week-old females, and the average weight was a normal group without surgery, a sham group without ovarian resection, and an ovarian resection group with surgery. Rats were classified in the same way. Rats in which female menopausal symptoms were induced were prepared by resecting the rat ovaries through the above method.
- Cordyceps militaris concentrate according to Example 1 was administered to the ovariectomy group at a dose of 37.5, 75, 150 mg/kg once a day, and this was named as Cordyceps militaris concentrate administration group.
- distilled water DW
- ⁇ -estradiol 0.01 mg/kg of ⁇ -estradiol was administered once a day to the ovariectomy group as a positive control group, and this was named as the ⁇ -estradiol administration group.
- Cordyceps militaris concentrate according to Example 1 to measure the change in fat mass in the female menopausal symptom induction animal model, the dual energy X-ray absorption method (the dual energy X) using INALYZER (MEDIKORS) whole body of each experimental rat. -ray absorptiometry) was used to analyze body fat.
- Example 1 In order to evaluate the effect of the cordyceps militaris concentrate according to Example 1 on the serum lipid composition in the female menopausal symptom induction animal model, blood was collected from each experimental rat, and the Accute TBA-40FR kit (Toshiba Medical Systems Co. , Japan) according to the manufacturer's protocol to measure the blood content of triglyceride (TG), total cholesterol (CHOL), high-density lipoprotein (HDL), and low-density lipoprotein (LDL).
- TG triglyceride
- CHOL total cholesterol
- HDL high-density lipoprotein
- LDL low-density lipoprotein
- Example 1 When the Cordyceps militaris concentrate according to Example 1 was treated with 5, 10 and 25 ⁇ g/mL according to Method 3, the cell proliferation effect was improved as the concentration increased to 107.9%, 126.1% and 135.7%, respectively. It was confirmed that, when treated with ICI 182,780 at the same time, cell proliferation was inhibited (see FIG. 1).
- the existing female menopausal treatment, Queen's Expedition increases MCF-7 by 11.2% at a concentration of 25 ⁇ g/mL
- the Cordyceps militaris concentrate according to Example 1 is MCF-7 cells at a concentration of 25 ⁇ g/mL.
- MCF-7 cells were treated with 10, 25 ⁇ g/mL of Cordyceps militaris concentrate according to Example 1, and the expression level of pER ⁇ , a phosphorylated form of ER ⁇ and ER ⁇ , was measured by Western blot. Confirmed (see Fig. 3).
- Estrogen receptor alpha is a nuclear receptor that responds to estrogen. In MCF-7 cells, it is phosphorylated by estrogen stimulation to regulate signal transduction such as cell proliferation. In other words, the expression of phosphorylated ER ⁇ (pER ⁇ ) means that ER ⁇ was stimulated equal to estrogen.
- cordyceps militaris concentrate according to Example 1 has estrogen activity, so it has been proven that there is an effect of treating and improving female menopausal symptoms caused by female hormone reduction.
- Cordyceps militaris concentrate according to Example 1 was measured according to the ⁇ Method 5> after 8 weeks to confirm the obesity induction phenomenon in the female menopausal symptom induction animal model.
- the ovarian resection group in which the female menopause was induced by resecting the ovary increased weight compared to the group (sham) who performed only laparotomy without resecting the ovary, thereby removing the ovary.
- obesity a female menopausal symptom induced according to, was induced.
- the weight gain was suppressed compared to the ovariectomy group in the cordyceps militaris concentrate administration group (37.5, 75 and 150 mg/kg) according to Example 1.
- the cordyceps militaris concentrate administration group (150 mg/kg) according to Example 1 showed an effect of suppressing weight gain of about 46% than the ⁇ -estradiol administration group, which is a positive control.
- diet intake was measured at 8 weeks of each experimental group (see FIG. 5). Specifically, it was confirmed that dietary intake increased in the ovarian resection group compared to the group (sham) who performed only laparotomy without resecting the ovaries. And, in the cordyceps militaris concentrate administration group according to Example 1, dietary intake was decreased compared to the ovariectomy group.
- the rats whose female menopausal symptoms were induced due to the removal of the ovaries gained weight and increased dietary intake to induce obesity, but weight gain was suppressed in the Cordyceps militaris concentrate administration group according to Example 1. It was confirmed that the induction of obesity in rats was suppressed. That is, it was proved that the cordyceps militaris concentrate according to Example 1 has the effect of preventing and improving obesity induced by female menopause.
- triglyceride and LDL levels in the ovariectomized group were increased compared to the non-ovarian resected rats. However, it was confirmed that triglyceride and LDL levels were reduced in the cordyceps militaris concentrate administration group (37.5, 75 and 150 mg/kg) according to Example 1. In addition, in the cordyceps militaris concentrate administration group (37.5, 75, and 150 mg/kg) according to Example 1, it was confirmed that HDL levels increased and cholesterol levels decreased.
- the triglyceride and LDL levels inducing obesity and vascular disorders were increased by female menopause due to ovariectomy, but the concentrate of Cordyceps militaris according to Example 1 inhibited the improvement of triglyceride and LDL levels. Proved to be. That is, the above results proved that the Cordyceps militaris concentrate according to Example 1 is effective in preventing and treating obesity and vascular disorder symptoms induced by female menopause.
- Tablets were prepared by mixing the above ingredients and tableting according to a conventional tablet preparation method.
- the above ingredients were mixed and filled into gelatin capsules according to a conventional capsule preparation method to prepare a capsule.
- the above ingredients were mixed according to a conventional method for preparing a liquid formulation, filled in a 100 ml brown bottle, and sterilized to prepare a liquid formulation.
- the present invention relates to a female menopausal symptoms, prevention or therapeutic composition
- Cordyceps (Cordyceps militaris) concentrate of the present invention is the estrogenic activity and proven, female woman in menopause induced animal models of By reducing the weight gain, diet increase, body fat and abdominal fat induced by menopause, there is an excellent effect in preventing or improving female menopausal symptoms and obesity associated with female menopausal symptoms.
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Abstract
La présente invention concerne une composition pharmaceutique pour prévenir ou traiter les symptômes de la ménopause chez la femme, ou une composition alimentaire pour prévenir ou diminuer les symptômes de la ménopause chez la femme, comprenant un concentré de Cordyceps militaris. Le concentré de Cordyceps militaris de la présente invention présente une activité oestrogénique prouvée et limite l'augmentation de poids, l'augmentation de la prise alimentaire, la graisse corporelle et la graisse abdominale, lesquels sont induits par la ménopause chez la femme dans un modèle animal qui reproduit, de façon induite, la ménopause de la femme, et possède de ce fait un excellent effet de prévention ou de diminution des symptômes de la ménopause chez la femme et de l'obésité accompagnant les symptômes de la ménopause chez la femme.
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KR1020190062648A KR20200136721A (ko) | 2019-05-28 | 2019-05-28 | 동충하초 농축액을 유효성분으로 포함하는 여성 갱년기 증상 예방 또는 치료용 조성물 |
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CN114028435A (zh) * | 2021-12-17 | 2022-02-11 | 深圳晨雾健康科技有限公司 | 含有蛹虫草提取物的雾化液及其用途 |
US12060328B2 (en) | 2022-03-04 | 2024-08-13 | Reset Pharmaceuticals, Inc. | Co-crystals or salts of psilocybin and methods of treatment therewith |
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KR20220105361A (ko) | 2021-01-20 | 2022-07-27 | (주)뷰티나인 | 바이텍신을 유효성분으로 포함하는 여성 갱년기 증상의 예방 또는 개선용 조성물 |
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