Composition for preventing or ameliorating climacteric symptoms containing ergothioneine

By using ergothioneine or its salts to block ATP-sensitive potassium channels and phosphodiesterase, the side effects of hormone replacement therapy are solved, providing a safe and effective method for improving menopausal symptoms, and improving symptoms such as erectile strength, urogenital function and hair growth.

CN120640987APending Publication Date: 2025-09-12SUNTORY HLDG LTD
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Patent Information

Application Number
CN202480011219.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2023-02-16
Filing Date
2024-02-13
Publication Date
2025-09-12

AI Technical Summary

Technical Problem

In the prior art, long-term use of hormone replacement therapy to treat menopausal symptoms carries cancer risks and side effects. A safe and effective natural ingredient is needed to prevent or improve menopausal symptoms.

Method used

Ergothioneine or its salt is used as the active ingredient to prevent or improve menopausal symptoms such as muscle pain, decreased erectile strength, decreased urogenital function, and decreased hair quality by blocking ATP-sensitive potassium channels and phosphodiesterase 5 or phosphodiesterase 7A1.

Benefits of technology

Ergothioneine or its salts can safely and effectively prevent or improve menopausal symptoms, including improving blood flow, enhancing erectile strength, improving urogenital function, promoting hair growth, etc., without obvious side effects.

✦ Generated by Eureka AI based on patent content.

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Abstract

The purpose of the present invention is to provide a composition for preventing or ameliorating climacteric symptoms. The present invention relates to a composition for preventing or ameliorating climacteric symptoms, characterized by containing ergothioneine or a salt thereof as an active ingredient.
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Description

Technical Field

[0001] The present invention relates to a composition for preventing or improving menopausal symptoms, etc., containing ergothioneine. Background Art

[0002] Menopausal symptoms are caused by a decrease in the secretion of male or female hormones. In women, the decrease in estrogen secretion due to ovarian aging can trigger symptoms that appear approximately 2 to 10 years before and after menopause, including hot flashes, sweating, insomnia, depression, urinary incontinence, hair loss, muscle pain, and osteoporosis. In men, a decrease in testosterone levels can also lead to symptoms such as decreased erectile dysfunction, decreased libido, urinary problems, and abnormal cholesterol metabolism.

[0003] To prevent and treat these menopausal symptoms, hormone replacement therapy and non-steroidal preparations have been developed, and currently, hormone replacement therapy is the most effective method. However, long-term hormone use carries the risk of cancer, headaches, weight gain, and other side effects. Therefore, there is an urgent need for a safer ingredient that can prevent or improve menopausal symptoms and can be consumed daily as a food or beverage.

[0004] Ergothioneine is an amino acid contained in mushrooms, etc., and its L form exists naturally. Patent Document 1 discloses that applying a mushroom fruiting body extract containing ergothioneine, niacin, and pantothenic acid to the top of the head confirms a hair-thickening effect.

[0005] Patent Literature Patent Document 1: Japanese Patent Application Laid-Open No. 2009-275027 Summary of the Invention

[0006] However, Patent Document 1 does not describe any content regarding the hair-increasing effect of ergothioneine alone or its influence on menopausal symptoms.

[0007] An object of the present invention is to provide a composition for preventing or improving menopausal symptoms.

[0008] The present inventors conducted intensive studies to solve the above-mentioned problems and found that L-ergothioneine or a salt thereof has the effect of preventing or improving menopausal symptoms.

[0009] That is, although not limited to the following, the present invention relates to the following compositions for preventing or improving menopausal symptoms. [1] A composition for preventing or improving menopausal symptoms, characterized in that it contains ergothioneine or a salt thereof as an active ingredient. [2] The composition according to [1] above, wherein the menopausal symptom is at least one symptom selected from the group consisting of muscle pain, decreased erectile strength, decreased genitourinary function, decreased hair volume and / or quality, and decreased energy. [3] The composition according to [1] or [2] above, wherein the menopausal symptoms are male menopausal symptoms. [4] The composition according to any one of [1] to [3] above, characterized in that it prevents or improves menopausal symptoms through ATP-sensitive potassium channels. [5] The composition according to any one of [1] to [4] above, characterized in that it inhibits phosphodiesterase 5 or phosphodiesterase 7A1. [6] The composition according to any one of [1] to [5] above, which is a composition for oral administration. [7] The composition according to any one of [1] to [6] above, which is a food or beverage. [8] The composition according to any one of [1] to [7] above, characterized in that it is marked with at least one function selected from "preventing menopausal symptoms", "improving menopausal symptoms", "assisting hormone deficiency in middle-aged and elderly people", "improving reproductive function in middle-aged and elderly people", "improving urination disorders in middle-aged and elderly people", "preventing hair loss in middle-aged and elderly people", "improving hair loss in middle-aged and elderly people" and "improving decreased energy in middle-aged and elderly people". [9] A method for preventing or improving menopausal symptoms, characterized in that ergothioneine or a salt thereof is administered to a subject.

[10] An application characterized in that ergothioneine or its salt is used to prevent or improve menopausal symptoms.

[0010] According to the present invention, a composition for preventing or improving menopausal symptoms can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 This is a graph showing the evaluation of the phosphodiesterase 5 inhibitory activity by L-ergothioneine. Figure 2 This is a graph showing the evaluation of the inhibitory activity of phosphodiesterase 7A1 by L-ergothioneine. Figure 3 This is a graph showing the evaluation of the substrate binding inhibitory activity of L-ergothioneine-based ATP-sensitive potassium channels. DETAILED DESCRIPTION

[0012] The composition for preventing or improving menopausal symptoms of the present invention contains ergothioneine or a salt thereof as an active ingredient. Hereinafter, the composition for preventing or improving menopausal symptoms of the present invention is also referred to as the composition of the present invention. Ergothioneine is a type of sulfur-containing amino acid. In the present invention, ergothioneine is preferably L-ergothioneine. As the salt of ergothioneine, as long as it is a salt allowed in pharmacology or a salt allowed in a diet, it is not particularly limited and can be any of an acidic salt and a basic salt. As an acidic salt, for example, inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate can be listed; organic acid salts such as acetate, citrate, maleate, malate, oxalate, lactate, succinate, fumarate, propionate, etc. can be listed. As a basic salt, for example, alkali metal salts such as sodium salt, potassium salt can be listed; alkaline earth metal salts such as calcium salt, magnesium salt, etc.

[0013] Ergothioneine or its salt is not limited by its form or production method. Ergothioneine or its salt can be chemically synthesized or extracted and purified from natural sources. L-ergothioneine is abundant in the golden top mushroom (Golden / Yellow Oyster mushroom) (scientific name: Pleurotus cornucopiae var. citrinopileatus), which belongs to the genus Pleurotus of the family Pleurotaceae. L-ergothioneine is also found in mushrooms such as Agaricus bisporus (scientific name: Agaricus bisporus), white button mushrooms, portabella mushrooms, and gray oyster mushrooms (scientific name: Pleurotus ostreatus); shiitake mushrooms (scientific name: Lentinula edodes); maitake mushrooms (scientific name: Grifola Frondosa); Ganoderma lucidum (scientific name: Ganoderma lucidum); Hericium erinaceus (scientific name: Hericium erinaceus); Agrocybe aegerita (scientific name: Agrocybe aegerita); Chanterelles (scientific name: Cantharellus cibarius); Boletus edulis (scientific name: Boletus edulis); and Morchella esculenta (scientific name: Morchella esculenta). When obtaining L-ergothioneine from natural sources, extraction from Pleurotus eryngii is preferred. Ergothioneine or its salts can also be produced by microbial fermentation. Ergothioneine or its salts can also be isolated.

[0014] L-ergothioneine or its salt is contained in natural products or food and drink, is the compound with edible experience.Therefore, from the viewpoint of safety, think that ergothioneine or its salt is also less problematic even if for example long-term intake.According to the present invention, a kind of prevention or improvement composition of the menopausal symptoms of high safety can be provided.

[0015] Menopausal symptoms are symptoms caused by decreased secretion of male hormones or female hormones, and there are many of them. Therefore, compositions for preventing or improving menopausal symptoms are expected to exhibit multiple effects. The menopausal symptoms are preferably at least one symptom selected from the group consisting of muscle pain, decreased erectile strength, decreased urogenital function, decreased hair volume and / or quality, and decreased energy. Examples of decreased urogenital function include urinary dysfunction. Decreased energy refers to a decrease in mental or physical activity. In the present invention, the menopausal symptoms may be male or female menopausal symptoms, but are preferably male menopausal symptoms. Examples of male menopausal symptoms include, but are not limited to, the symptoms exemplified above.

[0016] As shown in the examples described below, L-ergothioneine has the effect of inhibiting the binding of substrates to ATP-sensitive potassium (KATP) channels. In addition, L-ergothioneine has the effect of inhibiting phosphodiesterase 5 (PDE5) and phosphodiesterase 7A1 (PDE7A1). It is known that the opening of ATP-sensitive potassium channels in vascular smooth muscle improves blood flow to hair tissue. Furthermore, it is known that the opening of mitochondrial ATP-sensitive potassium channels can inhibit apoptosis in hair matrix cells. Furthermore, it is known that the opening of ATP-sensitive potassium channels can promote the proliferation of dermal papilla cells. Therefore, ergothioneine or its salts can improve the loss of hair volume and / or quality by acting through KATP channels.

[0017] In addition, when PDE5 is blocked, the decomposition of cGMP related to the relaxation of vascular smooth muscle is inhibited, confirming the effect of vasodilation or smooth muscle relaxation. It is known that this effect increases blood flow or oxygen supply, improving urination disorders or erectile dysfunction in benign prostatic hyperplasia. In addition, it is known that when PDE5 is blocked, muscle damage after treadmill running is reduced in mice, and endurance performance is improved (J Appl Physiol (1985), 2019 Jun 1; 126 (6): 1737-1745). As described above, by blocking PDE5, it is possible to prevent or improve erectile dysfunction, urogenital function decline and energy decline. Ergothioneine or its salts can prevent or improve erectile dysfunction, urogenital function decline and energy decline by blocking PDE5.

[0018] Furthermore, it is known that by inhibiting PDE7A1, cytokine production is suppressed, exerting an anti-inflammatory effect. Furthermore, it is known that when substrate binding to KATP channels is blocked, KATP channels open and blood vessels dilate. By inhibiting inflammation, muscle pain can be prevented or improved. Furthermore, it is generally believed that by dilating blood vessels and improving blood flow, muscle pain can be prevented or improved. Therefore, ergothioneine or its salts can prevent or improve muscle pain by inhibiting PDE7A1 and / or by acting through KATP channels.

[0019] The compositions of the present invention are used to prevent or alleviate menopausal symptoms. Symptom prevention includes preventing onset, delaying onset, reducing the incidence of symptoms, and alleviating the risk of onset. Symptom amelioration includes recovering from the symptoms, alleviating the symptoms, improving the symptoms, and delaying or preventing the progression of symptoms. Recovery includes partial recovery.

[0020] The composition of the present invention may be either an oral composition or a parenteral composition, but is preferably an oral composition. As oral composition, specifically can enumerate food and drink product, oral pharmaceutical product, medicine quasi-product etc., be preferably food and drink product or oral pharmaceutical product, more preferably food and drink product.Composition of the present invention also can be for being deployed in the material or preparation etc. used in food and drink product, pharmaceutical product, medicine quasi-product etc.

[0021] The composition of the present invention can be used for either therapeutic (medical) or non-therapeutic (non-medical) applications. The term "non-therapeutic" refers to a concept that does not include medical procedures, i.e., human surgery, treatment, or diagnosis.

[0022] Composition of the present invention, as long as not damaging the effect of the present invention, except thioneine or its salt, can contain any additive, any composition.These additives and composition can be selected according to the form etc. of composition.When composition of the present invention is made into oral composition, additives etc. that can be generally used for oral composition such as food and beverage, pharmaceuticals, quasi-medicine can be used.

[0023] When the composition of the present invention is prepared as a food or beverage, a pharmaceutical product, a quasi-drug, or the like, the production method is not particularly limited, and the composition can be produced by a general method. The form of the oral composition of the present invention is not particularly limited, and may be solid (powder, granule, tablet, etc.), liquid, paste, or the like.

[0024] When such as compositions of the present invention are made into food and drink, various food and drink can be made in thioneine or its salt, allocating spendable composition (such as, food material, the food additive used as required etc.) in food and drink.Food and drink are not particularly limited, and such as general food and drink, health food, health supplement food, health drink, functional label food, specific health food, patient food and drink etc. can be enumerated.Above-mentioned health food, health supplement food, functional label food, specific health food etc. such as can be used in the various preparation forms such as fine granule, tablet, granule, powder, capsule, chewable, dry syrup, syrup, liquid, beverage, oral liquid, liquid food.

[0025] When pharmaceuticals or quasi-medicines are made into compositions of the present invention, for example, the carrier allowed in pharmacology can be allotted in thioneine or its salt, the additive etc. added as needed, make pharmaceuticals or quasi-medicines of various dosage forms.Such carrier, additive etc., for the material allowed in the pharmacology that can be used for pharmaceuticals or quasi-medicines, for example, one or more than two kinds of excipients, binding agents, disintegrants, lubricants, antioxidants, coloring agents etc. can be enumerated. As the mode of administration (intake) of pharmaceuticals or quasi-medicines, the mode of administration orally or parenterally (percutaneous, through mucosa, enteral, injection etc.) can be enumerated. When pharmaceuticals or quasi-medicines are made into compositions of the present invention, it is preferably made into oral pharmaceuticals or oral quasi-medicines. As the dosage form for oral administration of pharmaceuticals or quasi-medicines, liquid, tablet, powder, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewing agents etc. can be enumerated. Examples of dosage forms for parenteral administration include injections, drops, ointments, lotions, patches, suppositories, nasal preparations, and pulmonary preparations (inhalants).

[0026] The subject to whom the composition of the present invention is to be ingested or administered (also referred to as the subject of administration) is not particularly limited, but preferably is a human. In one embodiment, as the subject of administration, there can be listed subjects who need or hope to prevent or improve menopausal symptoms. As such subjects, for example, middle-aged and elderly people can be listed. In one embodiment, the composition of the present invention is preferably used as a composition for preventing or improving menopausal symptoms in middle-aged and elderly people. Middle-aged and elderly people include elderly people. Elderly people can be, for example, humans over 60 years old or over 65 years old. Middle-aged and elderly people can be, for example, humans over 40 years old. In one embodiment, among middle-aged and elderly people, the subject is preferably over 40 years old and under 70 years old. The subject of administration can be a healthy person. The composition of the present invention can be used on healthy people for the purpose of improving or preventing menopausal symptoms. In the present invention, a particularly preferred subject is a healthy human over 45 years old and under 65 years old.

[0027] The content of ergothioneine or a salt thereof contained in the composition of the present invention is not particularly limited and can be set according to its form and the like. The content of ergothioneine or a salt thereof contained in the composition of the present invention is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and is preferably 90% by weight or less, more preferably 50% by weight or less, for example, calculated as ergothioneine. In one embodiment, the content of thioneine or its salt contained in the composition of the present invention is preferably 0.0001 to 90% by weight, more preferably 0.001 to 50% by weight, calculated as thioneine. The content of thioneine or its salt can be measured by high performance liquid chromatography (HPLC).

[0028] In this specification, the amount converted to ergothioneine or an expression similar thereto refers to the amount of ergothioneine, and refers to the value obtained by multiplying the number of moles of the salt by the molecular weight of ergothioneine in the case of a salt of ergothioneine.

[0029] The composition of the present invention can be taken or administered in a suitable manner adapted to its form. In one embodiment, the composition of the present invention is preferably taken orally (orally administered). The dosage (also referred to as intake) of the composition of the present invention is not particularly limited, and may be appropriately set according to the dosage, administration method, and weight of the subject as long as the dosage can achieve the prevention or improvement of menopausal symptoms.

[0030] In one way, when the mankind (adult) is taken orally or the composition of the present invention is administered, its dosage is in the dosage (ergothioneine conversion) of thioneine or its salt, and is preferably more than 2mg per 1 day, more preferably more than 5mg, more preferably more than 7mg, in addition, is preferably less than 50mg, more preferably less than 25mg, more preferably less than 20mg. In one way, when the dosage of the composition of the present invention is in the dosage (ergothioneine conversion) of thioneine or its salt, for the mankind (adult), is preferably 2~50mg per 1 day, more preferably 5~25mg, more preferably 5~20mg, more preferably 7~20mg. Preferably, the above amount is divided into more than 1 time per day, for example, 1 time per day or multiple (for example 2~3 times) are taken or administered. In one way, preferably, the mankind is taken orally or the thioneine or its salt of the above amount is administered thereto. The above-mentioned dosage can be the dosage of every body weight 60kg. In one embodiment, the composition of the present invention can be used to allow humans, for example, to ingest or administer the above-mentioned amount of ergothioneine or a salt thereof per 60 kg body weight per day.

[0031] The content of ergothioneine or a salt thereof in the composition of the present invention is preferably in an adult's daily intake, calculated as ergothioneine, of 2 to 50 mg, more preferably 5 to 25 mg, further preferably 5 to 20 mg, and particularly preferably 7 to 20 mg.

[0032] The composition of the present invention may also be labeled with a functional claim indicating a preventive or ameliorative effect on menopausal symptoms, or a claim indicating a function achieved through such an effect. Examples of such claims include claims indicating prevention or amelioration of muscle pain; prevention or amelioration of erectile dysfunction; prevention or amelioration of urogenital dysfunction; prevention or amelioration of hair volume and / or quality; and prevention or amelioration of decreased stamina. The composition of the present invention may also be accompanied by an indication of at least one function selected from, for example, "preventing menopausal symptoms", "improving menopausal symptoms", "assisting hormone deficiency in middle-aged and elderly people", "improving reproductive function in middle-aged and elderly people", "improving urinary disorders in middle-aged and elderly people", "preventing hair loss in middle-aged and elderly people", "improving hair loss in middle-aged and elderly people" and "improving decreased energy in middle-aged and elderly people". In one embodiment, the composition of the present invention is preferably a food or beverage with the above-mentioned label. In addition, the above-mentioned label may also be a label indicating the purpose of obtaining the above-mentioned function. The above-mentioned label may be attached to the composition itself, or to the container or packaging of the composition.

[0033] As shown above, thioneine or its salt hinders the combination of substrate and KATP channel.Therefore, thioneine or its salt can be used as the active ingredient for hindering substrate from being combined with KATP channel and use.Containing thioneine or its salt as active ingredient for the substrate combination for KATP channel hindering composition is also one of the present invention. In addition, ergothioneine or its salt inhibits phosphodiesterase 5 or phosphodiesterase 7A1. Thus, ergothioneine or its salt can be used as an active ingredient for inhibiting phosphodiesterase 5, or as an active ingredient for inhibiting phosphodiesterase 7A1. A composition for inhibiting phosphodiesterase 5 containing ergothioneine or its salt as an active ingredient is also one of the present invention. In addition, a composition for inhibiting phosphodiesterase 7A1 containing ergothioneine or its salt as an active ingredient is also one of the present invention.

[0034] The present invention also includes the following method. A method for preventing or improving menopausal symptoms, characterized in that thioneine or a salt thereof is administered to a subject. The above-mentioned method may be a therapeutic method or a non-therapeutic method.

[0035] The present invention also includes the following applications. An application is characterized in that ergothioneine or a salt thereof is used to prevent or improve menopausal symptoms. The above applications may be therapeutic applications or non-therapeutic applications. By administering ergothioneine or a salt thereof to a subject, menopausal symptoms can be prevented or improved.

[0036] In the above-mentioned method and application, the preferred mode of thioneine or its salt is identical with the above-mentioned composition of the present invention. As thioneine or its salt, 1 kind of thioneine or its salt can be used, and 2 or more kinds can also be used. In the above-mentioned method and application, preferably more than 1 time a day, for example, 1 time a day~multiple times (for example 2~3 times) thioneine or its salt is administered to the object (making it take in). In the above-mentioned method and application, preferably oral administration (take in) thioneine or its salt. The above-mentioned application is preferably the application in the mankind.

[0037] In said method and application, use the thioneine or its salt that can obtain the amount (also can be called effective dose) of desired effect.The preferred dosage of thioneine or its salt or the object of administration etc. are identical with above-mentioned composition of the present invention.Thioneine or its salt can directly be administered, and also can be administered as the composition containing it.For example, above-mentioned composition of the present invention can also be used.

[0038] The present invention also includes the use of ergothioneine or a salt thereof for producing a composition for preventing or improving menopausal symptoms. The present invention also provides ergothioneine or a salt thereof for improving or preventing menopausal symptoms.

[0039] In this specification, numerical ranges expressed with lower and upper limits, i.e., "lower limit to upper limit," include both lower and upper limits. For example, a range expressed with "1 to 2" means from 1 to 2, inclusive. In this specification, upper and lower limits may be used as ranges based on any combination. Example

[0040] Hereinafter, the present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited thereto.

[0041] <Example 1> (Evaluation of phosphodiesterase inhibitory activity) To evaluate the molecular targets of L-ergothioneine, in vitro assays targeting phosphodiesterase 5 (PDE5) and phosphodiesterase 7A1 (PDE7A1) were conducted. Eurofins Panlabs performed the in vitro assays as described below.

[0042] (PDE5) PDE5 isolated from human platelets (manufactured by Eurofins Cerep) was used. 60 ng of PDE5 was incubated with L-ergothioneine (L-ergothioneine concentration: 100 μM or 1000 μM) in a buffer containing 44 mM Tris / HCl (pH 7.4), 3 mM MgCl2, 1.04 mM dithiothreitol (DTT), 0.03% bovine serum albumin (BSA), 2% glycerol, 200 mM NH4Cl and 0.1 μM Ci[3H]cGMP at 22°C for 30 minutes. After adding phosphodiesterase SPA microparticles (product number: RPNQ0150, manufactured by PerkinElmer), the luminescence was detected with a detector, and the inhibitory activity of L-ergothioneine was evaluated using the amount of [3H]5'GMP as an indicator. The [ 3The amount of [H]5'GMP in the reaction solution to which L-ergothioneine was added was taken as 100% of PDE5 activity. 3 The relative PDE5 activity (%) relative to the control was determined by measuring the amount of 5'GMP in the H-phase. The inhibitory activity (%) was determined by the following formula. Inhibitory activity (%) = 100 - (relative activity of PDE5 when L-ergothioneine is added)

[0043] (PDE7A1) Human transgenic PDE7A1 (manufactured by Eurofins Cerep) expressed in insect cells was used. 0.6 U of PDE7A1 was incubated with L-ergothioneine (L-ergothioneine concentration: 100 μM, 1000 μM) in a buffer solution containing 40 mM Tris / HCl (pH 7.4), 8 mM MgCl2, and 0.035 μM Ci [3H] cAMP at 22°C for 30 minutes. After adding phosphodiesterase SPA microparticles (Product No.: RPNQ0150, manufactured by PerkinElmer), the luminescence was detected with a detector, and the inhibitory activity of L-ergothioneine was evaluated using the amount of [3H] 5'AMP as an indicator. The [ 3 The amount of [H]5'AMP in the reaction solution to which L-ergothioneine was added was taken as 100% of PDE7A1 activity. 3 The relative activity (%) of PDE7A1 relative to the control was determined by measuring the amount of 5'AMP in the H-phase 5′-AMP. The inhibitory activity (%) was determined by the following formula. Inhibitory activity (%) = 100 - (relative activity of PDE7A1 when L-ergothioneine is added)

[0044] Figure 1 This is a graph showing the evaluation of the inhibitory activity of phosphodiesterase 5 by L-ergothioneine. Figure 2 This is a graph showing the evaluation of the inhibitory activity of phosphodiesterase 7A1 by L-ergothioneine. Figure 1 and Figure 2 The concentration (μM) on the horizontal axis represents the concentration of L-ergothioneine. L-ergothioneine exhibits inhibitory activity against PDE5 and PDE7A1. PDE5 is known to increase blood flow or oxygen supply through vasodilation or smooth muscle relaxation, thereby improving urogenital function decline such as urination disorders in benign prostatic hyperplasia or improving erectile dysfunction. Furthermore, it is known that inhibiting PDE5 can improve stamina, so it is speculated that it has a preventive or ameliorative effect on menopausal energy decline. Furthermore, it is known that inhibiting PDE7A1 can suppress cytokine production, exert anti-inflammatory effects, and prevent or improve muscle pain. Therefore, it is speculated that L-ergothioneine exhibits these effects by inhibiting PDE5 and PDE7A1.

[0045] <Example 2> (Evaluation of substrate binding inhibition activity of ATP-sensitive potassium channels) To evaluate the molecular target of L-ergothioneine, an in vitro assay targeting ATP-sensitive potassium (KATP) channels was conducted. The in vitro assay was commissioned by Eurofins Panlabs and performed as follows.

[0046] 400 μg of rat cerebral cortical membrane fraction (containing KATP channels, manufactured by Eurofins Cerep) was dissolved in 50 mM Tris-HCl buffer (pH 7.4) and 0.1 nM [ 3 [3H]Glyburide and L-ergothioneine (L-ergothioneine concentration: 100 μM or 1000 μM) were incubated together at 22°C for 60 minutes. Glyburide is a KATP channel inhibitor. Nonspecific binding was determined in the presence of 1 μM gliburide (without L-ergothioneine). When gliburide was present in excess, [3H]gliburide could not bind to the KATP channel, and the radioactivity detected at this time was nonspecific binding. The membrane fraction was washed and filtered through a filter membrane, and the substrate binding inhibition activity of L-ergothioneine was evaluated using radioactivity as an indicator. [ 3 The more [H] glibenclamide is present, the stronger the radioactivity of the membrane fraction.

[0047] Figure 3 This is a graph showing the evaluation of the substrate binding inhibitory activity of L-ergothioneine on ATP-sensitive potassium channels. The concentration (μM) on the horizontal axis represents the concentration of L-ergothioneine. The substrate of KATP channel is in conjunction with hindering activity (%) and is sought according to the following steps.The radioactivity of membrane fraction in the reaction solution (control) not containing L-ergothioneine is made as 100%, based on the radioactivity of membrane fraction in the reaction solution with L-ergothioneine, seek the relative activity (%) relative to control when adding L-ergothioneine (100 μM or 1000 μM).When L-ergothioneine hinders the combination of glibenclamide and KATP channel, the radioactivity of membrane fraction declines.Therefore, by deducting the relative activity (%) when L-ergothioneine adds from the radioactivity (100%) of the membrane fraction of control, seek the substrate for KATP channel and in conjunction with hindering activity (%).

[0048] L-ergothioneine exhibits binding inhibition activity against glibenclamide, a substrate, at ATP-sensitive potassium channels. Opening ATP-sensitive potassium channels in vascular smooth muscle is known to improve blood flow in hair tissue. Furthermore, opening mitochondrial ATP-sensitive potassium channels is known to inhibit apoptosis in hair matrix cells. Furthermore, opening ATP-sensitive potassium channels is known to promote proliferation of dermal papilla cells. Therefore, it is speculated that L-ergothioneine may improve the loss of hair volume and / or quality through the action of ATP-sensitive potassium channels. Furthermore, it is known that when substrate binding to KATP channels is blocked, KATP channels open and vasodilation occurs. It is generally believed that by dilating blood vessels and improving blood flow, muscle pain can be prevented or alleviated. Therefore, it is speculated that L-ergothioneine may prevent or alleviate muscle pain through ATP-sensitive potassium channels.

Claims

1. A composition for preventing or improving menopausal symptoms, characterized in that: Contains ergothioneine or its salt as an active ingredient.

2. The composition according to claim 1, characterized in that The menopausal symptoms are at least one symptom selected from the group consisting of muscle pain, decreased erectile strength, decreased urogenital function, decreased hair volume and / or quality, and decreased energy.

3. The composition according to claim 1 or 2, characterized in that The menopausal symptoms are male menopausal symptoms.

4. The composition according to claim 1 or 2, characterized in that Prevent or improve menopausal symptoms through ATP-sensitive potassium channels.

5. The composition according to claim 1 or 2, characterized in that Inhibits phosphodiesterase 5 or phosphodiesterase 7A1.

6. The composition according to claim 1 or 2, characterized in that It is a composition for oral use.

7. The composition according to claim 6, characterized in that For food and drink.

8. The composition according to claim 1 or 2, characterized in that The product is labeled with at least one function selected from the group consisting of "preventing menopausal symptoms", "improving menopausal symptoms", "assisting hormone deficiency in middle-aged and elderly people", "improving reproductive function in middle-aged and elderly people", "improving urinary dysfunction in middle-aged and elderly people", "preventing hair loss in middle-aged and elderly people", "improving hair loss in middle-aged and elderly people" and "improving decreased energy in middle-aged and elderly people".

9. A method for preventing or improving menopausal symptoms, characterized in that: Ergothioneine or a salt thereof is administered to the subject.

10. An application, characterized in that: Ergothioneine or its salt is used to prevent or improve the symptoms of menopause.

Citation Information

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