TW202342085A - Composition for ameliorating unpleasant state caused by menstruation - Google Patents

Abstract

The purpose of the present invention is to provide: a composition for ameliorating an unpleasant state related to menstruation, the composition being effective for an unpleasant feeling felt by females from first menstruation to menopause, in particular, a strongly unpleasant feeling felt by young females, the composition having anti-EMT activity and being commonly consumed as foodstuff; and a functional food containing said composition. The present invention prepares a composition for ameliorating an unpleasant state related to menstruation, containing plant-based polyphenol.

Description

Composition to improve discomfort associated with menstruation

The present invention relates to a composition and functional food that improve the discomfort associated with menstruation that is recognized by many women. More specifically, the present invention relates to a functional food that is effective for young women who are prone to feel strong discomfort or uneasiness even though no organic disorder in the reproductive system is particularly confirmed.

The discomfort associated with menstruation involves lower abdominal pain, low back pain, headache, nausea, diarrhea, bloating, depression, fatigue, or loss of appetite. Endometriosis, uterine fibroids, uterine adenomyoma, etc. are known to be causative diseases of these conditions. However, women who feel strong discomfort even though such organic disorders have not been specifically identified are not Not a few.

The above-mentioned tendency is particularly strong in young women who have not experienced childbirth. A state in which no organic disorder is specifically identified other than this discomfort is defined as functional dysmenorrhea (Non-patent Document 1), but the cause has never been specifically identified. In the sense of disease, it is considered sub-health.

In 2012, there were 8 million women in Japan with dysmenorrhea, which is a combination of functional dysmenorrhea and organic dysmenorrhea. In addition, the labor loss caused by women's menstrual symptoms was estimated by the Ministry of Economy, Trade and Industry in 2019 to be more than 490 billion yen per year (Non-patent Document 2), so it is called a serious social problem and not just women's menstruation. The severe discomfort associated with it cannot be exaggerated.

On the other hand, in the case of organic dysmenorrhea, the treatment method corresponding to the specific organic disorder is relatively clear. For functional dysmenorrhea, NSAIDs (Nonsteroidal Antiinflammatory) that can alleviate the pain that is the representative discomfort are mainly used. Drugs; nonsteroidal anti-inflammatory drugs). NSAIDs are analgesics that are taken immediately when you feel pain, so of course they cannot improve the physical condition of a person who does not feel pain. It is believed that the psychological shadow of the pain every month is the cause of premenstrual syndrome (PMS; Premenstrual Syndrome) or premenstrual dysphoric disorder (PMDD; Premenstrual Dysphoric Disorder), which is a type of psychosomatic disorder. NSAIDs are taken after feeling pain. Difficulty improving PMS or PMDD. In addition, when the pain is too severe, there are also treatments that use estrogen drugs to prevent menstruation, which is the source of the pain. In addition, there are treatments that inhibit the maturation of follicles or the proliferation of the endometrium by administering a small amount of estrogen, thereby alleviating dysmenorrhea, but there are also mental disorders that force changes in the natural endocrine secretion of the original hormone ( hurdle) or side effects, according to a questionnaire survey on patients with dysmenorrhea, the actual use of estrogen drugs is an extremely low 7.5% (Non-patent Document 3).

In addition, women have recently entered society more and more, and as a result, late marriage has become a social trend. Dysmenorrhea can occur from menarche to menopause, but it is said that the symptoms of functional dysmenorrhea are more severe in young women who have not yet given birth. Due to late marriage, the social problem of labor loss caused by dysmenorrhea has become larger, so It is strongly hoped that a radical solution can solve the serious troubles and social losses of these women.

On the other hand, in recent years, the mechanism of dysmenorrhea has been increasingly clarified. Whether it is functional dysmenorrhea or organic dysmenorrhea, the fundamental mechanism is pointed out to be the transformation of endometrial epithelial cells (Epithelial-Mesenchymal Transition {hereinafter referred to as EMT}) (Patent Document 1, Patent document 2). Tranilast, a drug actually confirmed to have anti-EMT activity, was administered to patients with dysmenorrhea, and the results were confirmed by NRS (Numeric Rating Scale) scores in menstrual pain. Significant improvements have been achieved (Patent Document 1, Patent Document 2). There is a strong demand to improve the body's constitution so that menstruation-related discomfort is less likely to be felt by ingesting such safe ingredients with anti-EMT activity and few side effects. [Prior technical literature] [Patent Document]

[Patent Document 1] Japanese Patent No. 4709328. [Patent Document 2] Japanese Patent No. 5819599. [Non-patent literature]

[Non-patent document 1] Obstetrics and Gynecology Diagnosis and Treatment Guidelines - Gynecology Clinic 2017 [Non-patent Document 2] Ministry of Economy, Trade and Industry 2019 "Measures on Women's Health in Health Management" [Non-patent document 3] Bayer Yakuhin Co., Ltd. Press release on June 1, 2018 "Awareness and Fact Survey on Endometriosis and Menstrual Management"

[Problem to be solved by the invention]

The object of the present invention is to provide a composition with anti-EMT activity for improving discomfort related to menstruation and a functional food containing the composition, which can improve the discomfort of women from menarche to menopause, especially young women. Intense discomfort has an effect and a full feeding experience. [Means used to solve problems]

As a result of intensive research in view of the above-mentioned subject, it was found that a component derived from a specific plant has significant anti-EMT activity and is effective in improving discomfort related to menstruation, and the present invention was completed.

That is, the present invention provides the composition disclosed below. [1] A composition for improving discomfort associated with menstruation, containing plant-derived polyphenols with anti-EMT activity.

[2] The composition as described in [1], wherein the aforementioned plants are selected from the group consisting of apple, red rice, purple tea, lychee, acai berry, amla, cocoa, aronia, black currant, and Maqui Berry. At least one species from the group consisting of , black beans, and lingonberries.

[3] The composition according to [1] or [2], wherein the discomfort associated with menstruation is an discomfort occurring during menstruation or before menstruation.

[4] The composition according to any one of [1] to [3], wherein the discomfort associated with menstruation is selected from the group consisting of lower abdominal pain, low back pain, abdominal distension, headache, nausea, anemia, dizziness when standing, diarrhea, and fatigue. , fatigue, depression, emotional instability (anxiety, etc.), decreased concentration, drowsiness, chest swelling (breast pain), lower abdominal swelling, edema, stiff shoulders, rough skin, decreased appetite, increased appetite, decreased efficiency At least one of the following groups: , chills or sweating, weight gain, and conditions that cause difficulties in daily life.

[5] The composition according to any one of [1] to [4], which is an oral preparation. [Effects of the invention]

The composition of the present invention can effectively improve the discomfort related to menstruation, especially the strong discomfort that is easy to occur in young women, by containing ingredients with sufficient ingestion experience and anti-EMT activity.

The composition of the present invention contains plant-derived polyphenols with anti-EMT activity as active ingredients. In recent years, the mechanism has been continuously clarified, and it is expected that it can fundamentally improve the discomfort related to menstruation.

In this specification, the active ingredient is not particularly limited as long as it is a plant-derived polyphenol with anti-EMT activity. Although not limited, such active ingredients are preferably raw materials with experience in ingestion in the field of food and beverages and/or components derived from the raw materials.

[Plant-derived polyphenols with anti-EMT activity] Plant-derived polyphenols with anti-EMT activity may be contained in the form of a single polyphenol substance, or in the form of a plant containing polyphenols and other components (other than polyphenols) and/or an extract of the plant.

The plant-derived polyphenols having anti-EMT activity are not particularly limited as long as they show anti-EMT activity. Examples thereof include: anthocyanins (for example, cyanidin, delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin, etc.); flavanols (for example, procyanidin, catechin, epicatechin betaine, epigallocatechin, epicatechin gallate, epigallocatechin gallate, theaflavins, etc.); anthocyanins (e.g., cyanidin-3 - Glucoside (C3G), cyanidin-3-rutinoside (C3R), delphinidin-3-rutinoside (D3G), delphinidin-3-rutinoside (D3R)); flavonoids (e.g., cyanidin Apigenin, lutein, aurein, etc.); flavonols (for example, Quercetin, Kaempferol, Myricetin, Isorhamnetin, etc. ); Isoflavones (for example, Daidzein, Genistein, Glycitein); Tannins (for example, Pentagalloylglucose, etc.) ; and Ellagitannins (for example, Pedunculagin, Tellimagrandin I, Casuarinin, Tellimagrandin II), rugosin C (Rugosin C, etc.); brown algae polyphenols (Phlorotannin) (for example, phloroglucinol, etc.); other flavonoids (for example, resveratrol (Resveratrol), etc.), etc.

Among plant-derived polyphenols having anti-EMT activity, from the viewpoint of significantly exerting the effects of the present invention, for example, those selected from the group consisting of anthocyanins, flavanols, anthocyanins, flavonoids, and flavonols, preferably at least one selected from the group consisting of cyanidin, delphinidin, procyanidin, catechin, epicatechin, epigallocatechin, and epigallocatechin. Theaflavins, epigallocatechin gallate, theaflavins, cyanidin-3-glucoside (C3G), corianderin, quercetin, and kanfeflavonoids At least one of the group consisting of alcohols, more preferably selected from the group consisting of cyanidin, delphinidin, procyanidin, cyanidin-3-glucoside (C3G), cyanidin, and quercetin. and at least one of the group consisting of non-flavonols, more preferably protocyanidin, further preferably selected from the group consisting of protocyanidin B1, protocyanidin B2, and protocyanidin C1 At least one of them, preferably procyanidin B2.

The number of plant-derived polyphenols having anti-EMT activity may be one type, or two or more types.

Among the plant-derived polyphenols having anti-EMT activity, the plant used as the base is not limited as long as the effect of the present invention is exerted. For example, a polyphenol selected from the group consisting of apple, red rice, purple tea, lychee, At least one kind selected from the group consisting of acai berries, amla, cocoa, aronia, black currants, maqui berries, black beans, and lingonberries can be further preferably used selected from the group consisting of apples, lychees, wildflowers, At least 1 species from the group consisting of cherry berries, black currants, and black beans.

The parts of the plant are not limited as long as the effects of the present invention are exerted. Examples thereof include leaves, stems, stems, flowers, roots, seed coats, pericarp, fruits, germs, and the like.

When using an extract as a plant-derived polyphenol having anti-EMT activity, a known method can be used as long as the effect of the present invention is exerted, and the extraction method is not limited. The extract may be a crude extract extracted from a plant itself, or may be obtained by purifying the crude extract, or may be obtained by concentrating the crude extract, or a commercially available product may be used. The method for obtaining the extract is not particularly limited, and general extraction methods, purification methods, concentration methods, synthesis methods, drying and powdering methods, etc. can be used.

The extraction solvent for the extract is not limited as long as the effect of the present invention is exerted. For example, lower alcohols with 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropyl alcohol, butanol, etc.; glycerin , propylene glycol, polyethylene glycol and other polyols; water, acetone, ethyl acetate, methyl acetate and other polar solvents; hexane, pyridine and other non-polar solvents. Among these solvents, one type or any mixture of two types may be used. Among these solvents, water, ethanol, 1,3-butanediol, propylene glycol, or a mixed solution of these solvents is preferred, and a mixed solution of water and ethanol (aqueous ethanol) is more preferred.

The above-mentioned extract is not limited as long as the effect of the present invention is exerted. For example, the content of polyphenols in the extract is preferably 3 mass% or more, more preferably 5 mass% or more, and still more preferably 10 mass% or more. , particularly preferably 12 mass% or more, and most preferably 15 mass% or more. The content of polyphenols is not limited, and can be measured, for example, by the Folin-Denis method.

Among the plants known to be the basis, apples or apple extracts contain polyphenols derived from apples, and protocyanidin is the main component. The apples used are not limited, but from the viewpoint of significantly exerting the effects of the present invention, young fruits (underripe apples) are preferred. For example, polyphenols derived from apples can be obtained from the juice or extract of the fruits and/or peels of young apples (also known as underripe apples or unripe apples) by known means, and can be concentrated if necessary. , dilution, purification, drying and other treatments. In this manual, the so-called young apples refer to the fruits before they are displayed in stores as apple products.

Examples of procyanidin include polymers having the following formula 1 as a basic skeleton, and are not particularly limited. From the viewpoint of in vivo absorbability, a dimer or a trimer is preferred.

[Chemical 1]

Examples of dimers of procyanidin include procyanidin B1 and procyanidin B2, and examples of trimers of procyanidin include procyanidin C1 and the like.

Protocyanidin B1 is a compound represented by the following formula 2.

[Chemicalization 2]

Protocyanidin B2 is a compound represented by the following formula 3.

[Chemical 3]

Protocyanidin C1 is a compound represented by the following formula 4.

[Chemical 4]

Examples of commercially available products of apple-derived polyphenols include: ApplePhenon SH (manufactured by BGG Japan Co., Ltd.), ApplePhenon C-100 (manufactured by BGG Japan Co., Ltd.), apple procyanidin (apple-derived polyphenols) Protocyanidin 18.4% or more) (manufactured by BGG Japan Co., Ltd.), apple polyphenols (manufactured by ACCESS ONE Co., Ltd.), etc.

Among the plants known to be the basis, red rice or red rice extract contains polyphenols derived from red rice, with proanthocyanidins as the main component. Regarding red rice, brown rice is reddish-brown in color and contains red pigments in its peel, seed coat, etc. The variety of red rice is not limited as long as the effect of the present invention is exerted. Examples include: Benisuzaku, Beniasuka, Taoyuan, Benikicchou, Nakanoshima red rice ( Nakanoshimaakaimai), Beniakane, etc., only one type may be used, or two or more types may be mixed and used. For example, polyphenols derived from red rice can be obtained from red rice extracts by known methods, and can be concentrated, diluted, purified, dried, and other treatments as necessary.

Commercially available products of polyphenols derived from red rice include, for example, red rice extract-WSPC (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), red rice extract-PC (manufactured by Oryza Oil & Fat Chemical Co., Ltd.). company), red rice extract-LC (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), etc.

Among plants that are known to be the base, purple tea or purple tea extract contains polyphenols derived from purple tea, with anthocyanins as the main component. Purple tea has a purple color due to anthocyanins contained in tea leaves and the like. As purple tea, purple tea produced in Kenya (variety name TRFK306, etc.), Sun Rouge (National Research Institute of Agriculture and Food Industry Technology), etc. are known. Only one type of these purple teas may be used, or two or more types may be mixed and used. For example, polyphenols derived from purple tea can be obtained from purple tea extracts by known methods, and can be concentrated, diluted, purified, dried and other treatments as necessary.

Examples of commercially available products of polyphenols derived from purple tea include purple tea extract-LC (manufactured by Oryza Oil & Fat Chemical Co., Ltd.).

Among the plants that serve as bases, lychee or lychee extract contains polyphenols derived from lychee such as colorless cyanidin and anthocyanins. Litchi belongs to the Sapindaceae plant Litchi (Litchi chinensis Sonn.). For example, one or more parts of the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, sap, etc. can be used. Among these parts, peels, fruits, and seeds are preferred, and seeds are more preferred. For example, the polyphenols derived from lychee can be obtained from the juice or extract of lychee fruits, peels, and/or seeds by known means, and may be concentrated, diluted, purified, dried, etc. as necessary.

Commercially available products of polyphenols derived from lychee include, for example, lychee seed extract-P (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), lychee seed extract-WSP (Oryza Oil & Fat Chemical Co., Ltd.) (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), lychee seed extract-PC (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), lychee seed extract-LC (manufactured by Oryza Oil & Fat Chemical Co., Ltd.), etc.

Among the plants that serve as bases, acai berry or acai berry extract contains cyanidin-3-glucoside, pelargonidin-3-glucoside, ferulic acid, (-)-epicatechin, and gallic acid. acid, Turkish tannic acid and other polyphenols derived from acai berries. The acai berry belongs to the plant Euterpe oleracea of the family Palmaceae. For example, one or two pieces of the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, sap, etc. can be used. More than one part. Among these parts, peels, fruits, and seeds are preferred, and seeds are more preferred. For example, polyphenols derived from acai berries can be obtained from the juice or extract of acai berry fruits, peels, and/or seeds by known means, and may be concentrated, diluted, purified, dried, etc. as necessary. handle.

Examples of commercially available products of polyphenols derived from acai berries include acai berry extract (manufactured by Bio Actives Japan Co., Ltd.).

Among the plants that serve as bases, Phyllanthus emblica or Phyllanthus emblica extract contains sources of gallic tannins such as Elaeocarpusin, Chebulagic acid, and Geraniin. Polyphenols derived from Phyllanthus emblica. Phyllanthus emblica is a plant of Phyllanthus emblica. For example, one or more parts of the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, sap, etc. can be used. . Among these parts, fruits, bark, roots, and leaves are preferred, and fruits are more preferred. For example, the polyphenols derived from Phyllanthus emblica can be obtained from the juice or extract of Phyllanthus emblica fruits by known means, and may be concentrated, diluted, purified, dried, etc. if necessary.

Examples of commercially available products of polyphenols derived from Phyllanthus emblica include Phyllanthus emblica extract (manufactured by Bio Actives Japan Co., Ltd.).

Among the plants that serve as bases, cocoa or cocoa extract contains polyphenols derived from cocoa such as procyanidin. Theobroma cacao is the cacao tree (Theobroma cacao). For example, one or more parts such as the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, and sap can be used. Among these parts, seeds and fruits are preferred, and cocoa beans as seeds are more preferred. For example, polyphenols derived from cocoa are obtained by roasting cocoa beans, removing the skin and germ, and grinding the cocoa beans to produce cocoa mass. Then, sugar, milk powder, cocoa butter, etc. are added and thoroughly stirred to be processed into chocolate. In addition, cocoa powder is processed by removing fat and the like from the cocoa mass.

Examples of commercially available products of polyphenols derived from cocoa include cocoa bean extract (manufactured by Bio Actives Japan Co., Ltd.).

Among the plants that serve as bases, aronia or aronia extract contains polyphenols derived from aronia such as anthocyanins. Aronia melanocarpa Elliot is a small fruit tree of the Rosaceae family, also known as chokeberry. As aronia, for example, one or more parts such as the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, and sap can be used. Among these parts, fruits, bark, roots, and leaves are preferred, and fruits are more preferred. For example, the polyphenols derived from aronia can be obtained from the juice or extract of aronia fruit by known means, and may be concentrated, diluted, purified, dried and other processes as necessary.

Examples of commercially available products of polyphenols derived from aronia include aronia extract powder 35% (manufactured by BGG Japan Co., Ltd.).

Among the plants that serve as bases, blackcurrants or blackcurrant extracts contain polyphenols derived from blackcurrants such as anthocyanins. Blackcurrant belongs to the small fruit tree Blackcurrant (Ribes nigrum) of the genus Gooseberry in the family Ribesceae. It is also known as black currant, black currant (black sour block) and black currant. As the blackcurrant, for example, one or more parts such as the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, and sap can be used. Among these parts, fruits, bark, roots, and leaves are preferred, and fruits are more preferred. For example, the polyphenols derived from black currants can be obtained from the juice or extract of black currant fruits by known means, and can be concentrated, diluted, purified, dried, etc. if necessary.

Examples of commercially available products of blackcurrant-derived polyphenols include blackcurrant extract powder 35% (manufactured by BGG Japan Co., Ltd.).

Among the plants that serve as bases, maqui berry or maqui berry extract contains polyphenols derived from maqui berries, such as delphinidin and anthocyanins. Maquiberry is the fruit of Aristotelia chilensis, a plant of the family Aristotelia. For example, the polyphenols derived from the maqui berry can be obtained from the juice or extract of the maqui berry (fruit) by known means, and may be concentrated, diluted, purified, dried, etc. if necessary.

Examples of commercially available products of polyphenols derived from maqui berry include: maqui berry extract (manufactured by ACCESS ONE Co., Ltd.), maqui berry extract-P35 (manufactured by Oryza Oil & Fat Chemical Co., Ltd.) )wait.

Among the plants that serve as bases, black beans or black bean extracts contain polyphenols derived from black beans such as procyanidin. Black beans are soybeans (Glycine Max L.), and the seed coat is black. As black beans, for example, one or more parts such as the whole plant, leaves, flowers, stems, stems, branches, peels, fruits, seeds, bark, and sap can be used. Among these parts, the seed (black bean) and the seed coat (the skin of the black bean) are preferred, and the seed coat is more preferred. For example, polyphenols derived from black beans can be obtained from black bean extracts by known means, and can be concentrated, diluted, purified, dried, and other treatments as necessary.

Examples of commercially available products of polyphenols derived from black beans include ChronoCare SP15, ChronoCare SP60 (manufactured by Fujicco Co., Ltd.), and the like.

Among the plants that serve as bases, bilberry or bilberry extract contains polyphenols derived from bilberry such as anthocyanins. Vaccinium is the fruit of Vaccinium vitis-idaea L., a plant of the genus Vaccinium in the family Ericaceae. For example, polyphenols derived from bilberries can be obtained from bilberry (fruit) juice or extract by known means, and may be concentrated, diluted, purified, dried, and the like as necessary.

Examples of commercially available products of bilberry-derived polyphenols include LINGON MAX (manufactured by ACCESS ONE Co., Ltd.).

When an extract is used as a plant-derived polyphenol with anti-EMT activity, there is no restriction as long as the effect of the present invention is exerted. For example, it is preferably selected from the group consisting of apple extract, red rice extract, and purple tea extract. Composed of lychee extract, acai berry extract, amla emblica extract, cocoa extract, aronia berry extract, black currant extract, maqui berry extract, black bean extract, and bilberry extract At least one kind from the group, and more preferably at least one kind selected from the group consisting of apple extract, lychee extract, aronia extract, black currant extract, and black bean extract, and further More preferably, it is at least one selected from the group consisting of apple extract, lychee extract, and aronia extract. More preferably, it is an apple extract, and most preferably, it is an underripe apple extract.

In the composition of the present invention, the total content of plant-derived polyphenols with anti-EMT activity can be appropriately set according to the types of ingredients, the types and contents of other formulation ingredients, preparation form, usage method, etc. Although not limited, for example, in the case of a solid preparation, the total content of plant-derived polyphenols having anti-EMT activity is preferably 0.001 mass% or more, more preferably 0.005 mass%, based on the total amount of the composition. More preferably, it is 0.01 mass % or more, especially 0.05 mass % or more, still more preferably 0.1 mass % or more, most preferably 0.5 mass % or more. In addition, in the case of a solid preparation, the total content of plant-derived polyphenols with anti-EMT activity is preferably 95 mass% or less, more preferably 90 mass% or less, and particularly preferably 95 mass% or less based on the total amount of the composition. The content is 85% by mass or less, preferably 80% by mass or less. Regarding the total content of plant-derived polyphenols with anti-EMT activity, in the case of a solid preparation, it is preferably 0.001 mass % to 95 mass %, more preferably 0.005 mass % to 90 mass % relative to the total composition. %, more preferably 0.01 mass% to 85 mass%, particularly preferably 0.05 mass% to 80 mass%. Furthermore, in this specification, when a plant extract is used, the content of the plant extract is converted into dry solid content.

In the composition of the present invention, the total content of plant-derived polyphenols with anti-EMT activity can be appropriately set according to the types of ingredients, the types and contents of other formulation ingredients, preparation form, usage method, etc. Although not limited, for example, in the case of a liquid preparation, the total content of plant-derived polyphenols having anti-EMT activity is preferably 0.0001 mass % or more, and more preferably 0.0005 mass % relative to the total amount of the composition. More preferably, it is 0.001 mass % or more, especially 0.005 mass % or more, still more preferably 0.01 mass % or more, most preferably 0.05 mass % or more. In addition, in the case of a liquid preparation, the total content of plant-derived polyphenols with anti-EMT activity is preferably 25% by mass or less, more preferably 20% by mass or less, and particularly preferably 20% by mass or less based on the total amount of the composition. The content is 15% by mass or less, preferably 10% by mass or less. Regarding the total content of plant-derived polyphenols having anti-EMT activity, in the case of a liquid preparation, it is preferably 0.0001 mass % to 25 mass %, more preferably 0.0005 mass % to 20 mass % relative to the total amount of the composition. %, more preferably 0.001 mass% to 15 mass%, particularly preferably 0.005 mass% to 10 mass%. Furthermore, in this specification, when a plant extract is used, the content of the plant extract is converted into dry solid content.

[use] The composition of the present invention contains plant-derived polyphenols with anti-EMT activity as an active ingredient. In recent years, the mechanism has been continuously clarified, and it is expected to fundamentally improve the discomfort related to menstruation.

As mentioned above, in recent years, the mechanism of dysmenorrhea has been increasingly clarified. Dysmenorrhea is classified into functional (primary) dysmenorrhea and organic (secondary) dysmenorrhea.

Functional (primary) dysmenorrhea Although no organic disease has been confirmed in the pelvis, more than 90% of dysmenorrhea is functional (primary) dysmenorrhea. The pathogenesis of functional/organic dysmenorrhea is not fully understood yet, so no effective therapeutic drugs have been found. As described in Patent Document 1 and Patent Document 2, it was found that the endometrial epithelial tissue of healthy persons (those without dysmenorrhea) changes from a mesenchymal form to a high temperature phase during the transition period from the low-temperature phase of the basal body temperature before ovulation to the high-temperature phase. The morphological change is epithelial-like, but in patients with dysmenorrhea, the morphological change is prolonged, and the strong mesenchymal shape is maintained even after entering the high-temperature phase.

The search for an agent that normalizes this morphological change, that is, changes from mesenchymal to epithelial morphology, resulted in the discovery that tranilast has the ability to induce the leaf-like morphology between endometrial epithelial cells into an epithelial one. function (anti-EMT activity). Tranilast with anti-EMT activity was administered to multiple patients with dysmenorrhea for a certain period of time, and the effect of tranilast was verified. The results showed that the effect of tranilast on functional (primary) dysmenorrhea and organic (secondary) dysmenorrhea was Patients with any type of dysmenorrhea have found significant improvement in dysmenorrhea.

According to the findings described in the above-mentioned Patent Document 1 and Patent Document 2, if it is a component with anti-EMT activity, the morphological changes in the endometrial epithelial tissue can be maintained in a normal state, thereby suppressing and improving the accompanying symptoms. The phenomenon of menstrual discomfort.

Examples of uncomfortable conditions accompanying menstruation include lower abdominal pain, low back pain, bloating, headache, nausea, anemia, dizziness when standing, diarrhea, fatigue, lethargy, depression, emotional instability (anxiety, etc.), Decreased concentration, drowsiness, chest swelling (breast pain), lower abdominal swelling, edema, stiff shoulders, rough skin, decreased appetite, increased appetite, decreased efficiency, chills or sweating, weight gain, and obstruction to daily life At least one other physical state or mental state in the group of states. In this manual, these uncomfortable states may also be referred to as discomfort felt before menstruation or during menstruation. When the endometrial epithelial tissue does not undergo normal morphological changes and is delayed, it is speculated that the above-mentioned physical state will occur, and subsequently the above-mentioned physical state or mental state will also occur.

Examples of conditions that cause obstacles in daily life include: decreased efficiency in housework or work, absentmindedness in housework or work, reduced time for active activities, disordered life rhythm, lack of composure, and decreased concentration. , decreased enthusiasm for activities, a life of always sleeping, lack of energy, restlessness, depression and other obstacles.

In addition, regarding the discomfort associated with menstruation, sometimes there is a feeling of heaviness in the lower abdomen, a feeling of discomfort in the lower abdomen, a feeling of discomfort in the entire stomach, a feeling of heaviness in the whole body, and a feeling of being restrained (uncomfortable feeling). ), a feeling like stomach cramps, a heaviness in the back, a feeling like being unable to move, etc.

In this specification, the term "suppressing or improving the occurrence of discomfort associated with menstruation" means that the discomfort associated with menstruation does not occur, is alleviated, or is felt to be less severe as shown in the examples.

Symptoms associated with menstruation include: pain (lower abdominal pain, easy fatigue, shoulder stiffness, headache, low back pain/heaviness), discomfort in the lower abdomen as if a heavy constraint is attached, concentration (low concentration, insomnia) , making mistakes), changes in behavior (often staying at home, severe sleepiness, lack of perseverance in work), water retention (rough skin, small pustules, swelling, weight gain, breast swelling), emotional instability (becoming lonely) / Becoming restless, depressed, moody, restless, restless and irritable) and other related discomforts.

The discomfort associated with menstruation as shown in the example may not only occur during menstruation (during menstruation), but may also occur before menstruation. Sometimes the above physical or mental state will occur mildly from about 1 week to 2 weeks before menstruation. When the above-mentioned physical or mental state is strongly produced to the extent that it causes difficulties in daily life, it is called premenstrual syndrome (PMS). Although not limited, by using the composition of the present invention, premenstrual syndrome (PMS) or physical and/or mental discomfort 1 to 2 weeks before menstruation can be improved.

Especially those who suffer from severe menstruation, sometimes 1 to 2 weeks before menstruation, they will feel depressed mood, decreased enthusiasm, decreased concentration and other mental stress in anticipation of menstruation. Premenstrual mood disorder (PMDD) occurs when the mental stress that occurs about 1 to 2 weeks before menstruation is so intense that it causes difficulties in daily life. Although not limited, premenstrual mood disorder (PMDD) or mental stress 1 to 2 weeks before menstruation can be improved by using the composition of the present invention.

In addition, in the endometrium, if the endometrial tissue continues to undergo fibrosis due to EMT, it may also become the cause of infertility. As described above, the composition of the present invention can maintain the morphological changes in the endometrial epithelial tissue to a normal state by containing plant-derived polyphenols with anti-EMT activity as an active ingredient. Therefore, in another embodiment, the composition of the present invention can also be used for the prevention, progression inhibition, or treatment of infertility.

The composition of the present invention can be added to food and drink or mixed with these food and drink. Alternatively, it can be used directly as a drink or food. Alternatively, it can be added or mixed into functional foods such as food and beverages that are labeled as functional with text related to improving the discomfort associated with menstruation, that is, health foods, foods with functional labels, foods for patients, and foods for specific health uses. And use.

As a method of evaluating discomfort associated with menstruation, for example, the Menstrual Distress Questionnaire (MDQ) score can be used (Moos, R. H, Journal of Psychosomatic Medicine, 30: 853-867, 1968).

In the MDQ score, as evaluation factors, it can be classified into factors related to physical symptoms and factors related to mental symptoms. Examples of factors related to physical symptoms include: (1) Pain factors (stiff neck or shoulders, muscle pain, headache, lower abdominal pain, low back pain, easy fatigue, body aches), (2) Autonomic factors (dizziness and dizziness) , trance, chills or sweating, nausea, heat on the face), (3) water retention factor (weight gain, rough skin, small pustules, swollen breasts, edema in any of the abdomen, breasts, and feet), and (4) control factors (difficulty breathing, feeling of being constrained in the chest, tinnitus, numbness in hands and feet, blurred vision, and unclear vision).

Examples of factors related to mental symptoms include: (1) Concentration factor (insomnia, forgetfulness, indecision, slow judgment, decreased concentration, absentmindedness, mistakes, clumsy movements), (2) Action change factor (reflection on work) Lack of perseverance, dozing off, not wanting to get up, avoiding interacting with people, being too lazy to go out, reduced business efficiency), (3) Negative emotional factors (wanting to cry because of trivial things, feeling lonely, becoming restless, out of breath, and anxious, Irritability, changeable moods, wavering, worry, easily nervous), and (4) Emotional Elevation Factor (gentle mood, becoming open, excited, overflowing emotions, active).

As a method to evaluate pain during menstruation, for example, (1) scoring of subjective findings, (2) interrogation of other sensory findings, etc. described in the guidelines of the "Japanese Society of Palliative Medicine" can be used.

In the above (1) related to the guidelines of the "Japan Palliative Care Society", the intensity of pain (perceived by the user) in the lower abdomen or waist is rated from 0 (no pain at all) to 10 ( The 11 stages of unimaginable pain that makes it impossible to work (bedridden) are rated using the "Numeric Rating Scale (NRS)". In addition, in the above (2), by consulting a doctor once a month, the degree of disturbance to daily life is evaluated based on the pain.

Although not limited, for example, if a subject is allowed to ingest an ingredient with anti-EMT activity and an improvement is seen in at least one of the above evaluation items, it can be evaluated that the ingredient is effective for that evaluation item.

In addition, although it is not limited, when evaluating the uncomfortable state associated with menstruation, PMS memory (published by the Japan Family Planning Association) or the like may be used to record the daily state. PMS memory is not limited to diagnosing PMS, but is also used to record women's physical conditions. For example, when using PMS memory, the date, menstrual cycle, menstrual blood volume, basal weight, basal body temperature, symptoms and their extent, events, etc. can be recorded.

In addition to the above, standards for evaluating QOL (Quality of Life; quality of life) can also be used as an evaluation method for the discomfort associated with menstruation. Examples of such a standard include SF-36, which is one of the HR-QOL (Health-related QOL; health-related quality of life) standards, or a simplified version of SF-12v2, SF-8, or EQ-5D- 5L etc.

SF-36 is for (1) physical function, (2) daily functioning (body), (3) physical pain, (4) overall sense of health, (5) vitality, (6) social life function, (7) ) Daily functional functions (mental), (8) Psychological health 8 lower standards (items) are answered and scored to evaluate.

EQ-5D-5L is a questionnaire developed by the European Quality of Life Group (EuroQOL Group). It answers "degree of movement", "management of daily life", "daily activities", "pain or discomfort" and "uneasiness" on a 5-point scale. or depressed" 5 items.

[Dosage form] Regarding health foods, functionally labeled foods, foods for patients and foods for specific health purposes, specifically, they can be solid preparations (tablets, granules, fine granules, powders, capsules, chewable tablets, etc.) or liquid preparations (drinks). (preparations, syrups, suspensions), liquid foods, etc. Foods in the form of preparations can be produced in the same manner as known pharmaceutical preparations. The active ingredients can be mixed with a carrier acceptable as a food, such as an appropriate excipient, and then produced using conventional means.

For example, in the case of tablets, they can be prepared by mixing the powdered active ingredients with pharmaceutically acceptable carrier ingredients (excipients, etc.) and compression molding. Candy (caramel), etc. can be used to make pastry tablets by injection. into the mold for preparation. The tablets may also be sugar-coated to form sugar-coated tablets. Furthermore, the tablet may be a single-layer tablet or a laminated tablet such as a two-layer tablet.

Powders such as granules can be produced by various granulation methods (extrusion granulation, crushing granulation, dry compaction granulation, fluidized bed granulation, rolling granulation, high-speed stirring granulation, etc.) To prepare, tablets can be prepared by appropriately combining the above-mentioned granulation method, tableting method (wet tableting method, direct tableting method), etc.

Capsules can be prepared by filling powdered granules (powders, granules, etc.) into capsules (soft or hard capsules) using conventional methods.

The liquid preparation can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, ethanol-containing purified water, etc.) as a carrier component, filtering or sterilizing it as necessary, and filling it into a predetermined container. , perform sterilization treatment. The preferred dosage form of the solid preparation of the present invention is a capsule or a tablet, and more preferably a soft capsule (soft capsule, soft capsule).

Soft capsules are favored by users because they have a smooth surface and are easy to swallow. Examples of general soft capsule manufacturing methods include flat-plate type, rotary type, and seamless type.

In the manufacturing process of the rotating method (stamping method), a sheet-shaped capsule film is used to sandwich the flowing filling content, and the capsule shape is formed along the hole of the rotating cylindrical mold. On the other hand, the seamless method (dropping method) is manufactured by simultaneously spraying the capsule film composition and contents from multiple nozzles in concentric circles to form a seamless capsule shape.

The base of the film of the soft capsule is not particularly limited. Starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinate gelatin, etc. can be used. Starch, gelatin, succinate gelatin, and more are preferred. Gelatin, amber gelatin. These bases can be used alone or in combination of two or more.

In addition, the food composition can be produced into: soups, fruit juices, fruit drinks, milk, milk drinks, whey drinks, lactic acid bacteria drinks, tea drinks, herb tea and other black teas, alcoholic drinks, coffee drinks, carbonated Beverages, soft drinks, water drinks, cocoa drinks, jelly drinks, sports drinks, low-calorie drinks and other liquid drinks, pudding, yogurt and other semi-solid foods, noodles, snacks, spreads, etc.

Various food additives can also be blended into the food composition. Examples of food additives include antioxidants, pigments, fragrances, seasonings, sweeteners, sour agents, pH adjusters, quality stabilizers, and preservatives.

When preparing a pharmaceutical composition, the present invention is prepared into a preparation containing an ingredient with anti-EMT activity as an active ingredient, and preferably a pharmaceutically acceptable carrier. The so-called pharmaceutically acceptable carrier generally refers to inert, non-toxic, solid or liquid extenders, diluents or encapsulating materials that do not react with the aforementioned active ingredients. Examples include: water, ethanol, polyols , appropriate mixtures of these ingredients, solvents or dispersion media such as vegetable oils, etc.

The pharmaceutical composition is administered orally or parenterally, for example, into the oral cavity, digestive tract, or nasal cavity. Examples of preparations for oral administration include solid preparations (tablets, granules, fine granules, powders, capsules, chewable tablets, etc.), liquid preparations (syrups, suspensions, inhalants), and the like. Examples of preparations for parenteral administration include intravenous drops, nasal drops, injections, and the like.

The pharmaceutical composition may further include additives commonly used in the pharmaceutical field. Examples of such additives include excipients, binding agents, disintegrants, lubricants, antioxidants, colorants, flavoring agents, etc., which may be used appropriately as necessary. In order to achieve sustained release so that it can act for a long time, it can also be coated with a known delaying agent. The pharmaceutical composition may further add other additives or medicaments as necessary, such as antacids and gastric mucosal protective agents.

The pharmaceutical composition can be applied in the form of oral composition, oral composition, etc. In addition, the pharmaceutical composition can be used in a therapeutic manner or in a non-therapeutic manner.

The daily oral intake or dosage of an ingredient with anti-EMT activity for adults may vary depending on the individual's condition, weight, gender, age, activity of raw materials, route of intake or administration, schedule of intake or administration, preparation form, or and other factors as appropriate.

The daily oral intake or dosage of plant-derived polyphenols having anti-EMT activity for adults is, for example, preferably 0.001 mg/day or more, more preferably 0.005 mg/day or more, and still more preferably 0.01 mg/day. Above, it is particularly preferably 0.05 mg/day or more, and most preferably 0.1 mg/day or more. The daily oral intake or dosage of plant-derived polyphenols with anti-EMT activity for adults is, for example, preferably 2000 mg/day or less, more preferably 1500 mg/day or less, and still more preferably 1000 mg/day or less, especially The optimal dosage is below 800mg/day, and the optimal dosage is below 500mg/day. The daily oral intake or dosage of plant-derived polyphenols with anti-EMT activity for adults is, for example, preferably 0.001 mg/day to 2000 mg/day, more preferably 0.005 mg/day to 1500 mg/day, and more preferably The preferred range is 0.01 mg/day to 1000 mg/day, the preferred range is 0.05 mg/day to 800 mg/day, and the optimum range is 0.1 mg/day to 600 mg/day. The content of the plant-derived polyphenol having anti-EMT activity can be set to an amount that meets the above-mentioned intake amount or dosage amount. Furthermore, the daily oral intake or dosage for adults depends on the dosage form. For example, if it is a capsule, it can be divided into 1 capsule to 6 capsules, 1 capsule to 4 capsules, 1 capsule to 3 capsules, or 1 capsule to 2 capsules. Take capsules.

When apple extract is used as a plant-derived polyphenol with anti-EMT activity, the daily oral intake or administration amount of apple extract for adults is, for example, preferably 0.001 mg/day or more, more preferably 0.005 mg/day or more, more preferably 0.01 mg/day or more, especially 0.05 mg/day or more, most preferably 0.1 mg/day or more. In another embodiment, the daily oral intake or administration amount of apple extract for adults can be, for example, more than 1 mg/day, more than 10 mg/day, more than 50 mg/day, more than 100 mg/day, or more than 200 mg/day. , 300mg/day or more, 400mg/day or more, etc. In addition, the daily oral intake or dosage of apple extract for adults is, for example, preferably 2000 mg/day or less, more preferably 1500 mg/day or less, further preferably 1000 mg/day or less, particularly preferably 900 mg/day or less. , the best is less than 800mg/day. The daily oral intake or administration amount of apple extract for adults is, for example, preferably 0.001 mg/day to 2000 mg/day, more preferably 0.005 mg/day to 1500 mg/day, and still more preferably 0.01 mg/day to 1000 mg. /day, preferably 0.05mg/day to 900mg/day, optimally 0.1mg/day to 800mg/day. In another embodiment, the daily oral intake or administration amount of apple extract for adults can be, for example, 1 mg/day to 800 mg/day, 10 mg/day to 800 mg/day, 50 mg/day to 800 mg/day, 100mg/day to 800mg/day, 200mg/day to 800mg/day, 300mg/day to 800mg/day, 400mg/day to 800mg/day, etc.

In the apple extract, the content of procyanidin derived from apples is based on the total amount of the extract. For example, it can be more than 1 mass%, more than 5 mass%, more than 10 mass%, more than 11 mass%, or more than 12 mass%. , 13 mass% or more, 14 mass% or more, 15 mass% or more, etc.

When using apple-derived procyanidin as a plant-derived polyphenol with anti-EMT activity, the daily oral intake or administration amount of procyanidin for adults is preferably 0.001 mg/day or more, for example. More preferably, it is 0.005 mg/day or more, further preferably 0.01 mg/day or more, especially 0.05 mg/day or more, most preferably 0.1 mg/day or more. In another embodiment, the daily oral intake or administration amount of procyanidin for adults can be, for example, more than 1 mg/day, more than 10 mg/day, more than 20 mg/day, more than 30 mg/day, or more than 50 mg/day. , 100mg/day or more, etc. In addition, the daily oral intake or dosage of procyanidin for adults is, for example, preferably 1000 mg/day or less, more preferably 900 mg/day or less, further preferably 800 mg/day or less, especially 600 mg/day or less. , the best is less than 400mg/day. The daily oral intake or administration amount of procyanidin for adults is, for example, preferably 0.001 mg/day to 1000 mg/day, more preferably 0.005 mg/day to 900 mg/day, and still more preferably 0.01 mg/day to 800 mg. /day, preferably 0.05mg/day to 600mg/day, optimally 0.1mg/day to 400mg/day. In another embodiment, the daily oral intake or administration amount of procyanidin for adults can be, for example, 0.1 mg/day to 800 mg/day, 0.1 mg/day to 700 mg/day, or 0.1 mg/day to 600 mg. /day, 0.1mg/day to 500mg/day, 0.1mg/day to 400mg/day, 0.1mg/day to 300mg/day, 0.1mg/day to 200mg/day, etc.

[Applicable persons] There is no restriction on the use of the present invention in the field of food and beverages such as functional foods. For example, the application target may be those who have discomfort symptoms associated with menstruation. In addition, the application subjects may also be, for example, those who have not been diagnosed with dysmenorrhea, those who have not continued to go to the hospital for menstruation-related diagnosis and treatment, or those who have not continued to receive pharmaceutical formulas due to discomfort associated with menstruation. Those who do not feel any special discomfort except during menstruation or before menstruation can be said to be sub-healthy.

In addition, although there is no limitation, the application target may be those who have been excluded from organic dysmenorrhea after a doctor's consultation or examination. Organic dysmenorrhea can be ruled out through the following methods, that is, using a selection of internal examination, ultrasound examination, peripheral blood, CRP (C-reactive protein; c-reactive protein) examination, bacterial culture examination, chlamydia antigen It is judged that there is no abnormality by at least one of the group consisting of examination and imaging diagnosis.

In addition, the discomfort associated with menstruation tends to be more severe in young women. Therefore, the composition of the present invention can be used for adolescence (about 10 years old to about 18 years old), young adulthood (about 15 years old to about 30 years old), about 15 years old or above, or middle age (about 45 years old or above) to under 55 years old).

The present invention may also be in the following aspects. A composition for improving the discomfort associated with menstruation, containing plant-derived polyphenols with anti-EMT activity; a composition containing plant-derived polyphenols with anti-EMT activity, for improving the discomfort associated with menstruation. state; a use of a composition containing plant-derived polyphenols with anti-EMT activity to produce an agent for improving the discomfort associated with menstruation; a method for improving the discomfort associated with menstruation, including making a person ingest a substance containing A composition derived from plant polyphenols with anti-EMT activity; such as the above-mentioned composition, use, or method, wherein the aforementioned discomfort associated with menstruation is an discomfort that occurs during or before menstruation; such as the above-mentioned composition , use, or method, wherein the aforementioned discomfort accompanying menstruation is selected from lower abdominal pain, low back pain, abdominal distension, headache, nausea, anemia, diarrhea, fatigue, depression, emotional instability, decreased concentration, and drowsiness. , at least one of the group consisting of breast swelling (breast pain), edema, rough skin, loss of appetite, loss of efficiency, weight gain, and conditions that cause obstacles to daily life; such as the above compositions, uses, or Method, wherein the discomfort state produced before menstruation is premenstrual syndrome (PMS) or premenstrual mood disorder (PMDD); the above composition, use, or method, wherein the discomfort state produced before menstruation is premenstrual syndrome The physical and/or mental discomfort state 1 week to 2 weeks ago; a composition for improving dysmenorrhea, containing polyphenols derived from plants with anti-EMT activity; a composition containing polyphenols derived from plants with anti-EMT activity A composition of plant polyphenols for improving dysmenorrhea; a use of a composition containing plant-derived polyphenols with anti-EMT activity to produce a dysmenorrhea improving agent; a method for improving dysmenorrhea, including Allowing people to ingest a composition containing plant-derived polyphenols with anti-EMT activity; such as the above-mentioned composition, use, or method, wherein the aforementioned dysmenorrhea is functional (primary) dysmenorrhea or organic (secondary) dysmenorrhea. Sexual) dysmenorrhea; the above-mentioned composition, use, or method, wherein the plant-derived polyphenols with anti-EMT activity are selected from the group consisting of apple, red rice, purple tea, lychee, acai berry, At least one of the group consisting of amla, cocoa, aronia, blackcurrant, maquiberry, black bean, and bilberry; the above-mentioned composition, use, or method, wherein the aforementioned anti-EMT activity Polyphenols derived from plants are selected from apple extract, red rice extract, purple tea extract, lychee extract, acai berry extract, amla officinalis extract, cocoa extract, aronia berry extract, black At least one of the group consisting of galbanum extract, maquiberry extract, black bean extract, and bilberry extract; as in the above composition, use, or method, wherein the aforementioned apple extract is an apple larvae The juice or extract of the fruit and/or peel of the fruit; the composition, use, or method as described above, wherein the content of apple-derived procyanidin in the aforementioned apple extract is 1 mass % or more; as described above The composition, use, or method, wherein the plant-derived polyphenol with anti-EMT activity is a polyphenol derived from apples; the above-mentioned composition, use, or method, wherein the plant-derived polyphenol with anti-EMT activity The polyphenol is at least one selected from the group consisting of anthocyanins, flavanols, anthocyanins, flavonoids, and flavonols; such as the above composition, use, or method, The aforementioned plant-derived polyphenols with anti-EMT activity are selected from the group consisting of cyanidin, delphinidin, procyanidin, cyanidin-3-glucoside (C3G), corianderin, quercetin, and cyanidin. At least one of the group consisting of non-flavonols; the above-mentioned composition, use, or method, wherein the plant-derived polyphenol with anti-EMT activity is procyanidin B2; the above-mentioned composition, Uses, or methods, wherein the content of plant-derived polyphenols with anti-EMT activity in the case of solid preparations is 0.001 mass% to 95 mass%; compositions, uses, or methods as described above, wherein in the case of liquid preparations When the content of plant-derived polyphenols with anti-EMT activity is 0.0001 mass% to 25 mass%; as in the above composition, use, or method, it is an oral agent; as in the above composition, use, or Methods, which are solid preparations (for example, tablets, granules, fine granules, powders, capsules, chewable tablets) or liquid preparations (for example, drinks, syrups, suspensions); compositions and uses as described above , or a method, wherein the daily oral intake of polyphenols derived from plants with anti-EMT activity for adults is 0.001 mg/day to 2000 mg/day; the composition, use, or method as described above, wherein the polyphenols having anti-EMT activity are The daily oral intake of polyphenols derived from plants for adults is 0.01 mg/day to 1000 mg/day; as in the above composition, use, or method, wherein the polyphenols derived from plants for adults with anti-EMT activity The daily oral intake ranges from 0.1mg/day to 600mg/day; the above-mentioned composition, use, or method, the application (ingestion) target is adolescence (about 10 years old to about 18 years old), young adulthood (15 years old) Around 30 years old to around 30 years old), around 15 years old and above, or middle-aged (around 45 years old to below 55 years old). [Example]

Next, the present invention will be specifically explained through examples or test examples, but the present invention is not limited to the following examples or test examples.

As an extract of underripe apples, ApplePhenon (manufacturer: Bggjapan Co., Ltd.) was used. Underripe apple extract is obtained by extracting underripe apple fruits as raw materials. The content of cyanidin derived from apples in the extract is more than 15% by mass. In addition, the standard daily intake of the unripe apple extract is about 600 mg/day, and the standard daily intake of procyanidin derived from apples is about 110 mg/day. Although the data is not shown, the inventor of this case confirmed that the extract is rich in procyanidin B2 among procyanidins.

As the red rice extract, red rice extract-WSP (manufacturer: Oryza Oil & Fat Chemical Co., Ltd.) was used. Red rice extract is obtained by using red rice as raw material and extracting it with aqueous ethanol. The polyphenol content in the extract is 1% by mass or more.

As the purple tea extract, purple tea extract-P (manufacturer: Oryza Oil & Fat Chemical Co., Ltd.) was used. Purple tea extract is obtained by using purple tea leaves as raw materials and extracting them with aqueous ethanol. The polyphenol content in the extract is 30% by mass or more.

As the lychee extract, Oligonol (manufacturer: Amino Up Co., Ltd.) is used. The extract is rich in proanthocyanidins, etc.

As the acai berry extract, acai berry extract (manufacturer: Bio Actives Japan Co., Ltd.) was used. Acai berry extract is obtained by extracting the fruit of acai berry as raw material. The polyphenol content in the extract is 0.5% by mass or more.

As the extract of Phyllanthus emblica, Phyllanthus emblica extract (manufacturer: Bio Actives Japan Co., Ltd.) was used. The extract of Phyllanthus emblica is obtained by extracting the fruit of Phyllanthus emblica as raw material. The tannin content in the extract is 20% by mass or more.

As the cocoa extract, cocoa bean extract (manufacturer: Bio Actives Japan Co., Ltd.) is used. Cocoa extract is obtained by extracting cocoa seeds as raw materials.

As the aronia extract, aronia extract powder 35% (manufacturer: BGG Japan Co., Ltd.) was used. Aronia berry extract is obtained by extracting Aronia berry fruits as raw materials. The anthocyanin content in the extract is 35% by mass or more.

As the blackcurrant extract, blackcurrant extract powder 35% (manufacturer: BGG Japan Co., Ltd.) was used. Blackcurrant extract is obtained by extracting blackcurrant fruit as raw material. The anthocyanin content in the extract is 35% by mass or more.

As the extract of maqui berry, maqui berry extract (manufacturer: ACCESS ONE Co., Ltd.) is used. Maquiberry extract is obtained by extracting the fruit of Maquiberry as raw material. The extract is rich in anthocyanins, etc.

As the black bean extract, ChronoCare SP60 (manufacturer: Fujicco Co., Ltd.) was used. Black bean extract is obtained by extracting the skin of black beans as raw material. The polyphenol content in the extract is 58% by mass or more.

As the bilberry extract, bilberry extract-P0.5 (manufacturer: Oryza Oil & Fat Chemical Co., Ltd.) was used. Bilberry extract is obtained by extracting bilberry fruits as raw materials. The extract is rich in resveratrol, anthocyanins, procyanidin, etc.

In addition, in order to confirm the anti-EMT activity of each plant-derived polyphenol alone, the following commercially available raw materials were used. Cyanidin-3-glucoside (C3G) (Manufacturer: Nagara Science Co., Ltd.) Cyanidin (Manufacturer: Fujifilm Wako Pure Chemical Industries, Ltd.) Delphinidin (Manufacturer: Cayman Chemical Company) Corianderin (Manufacturer: Fuji Film Wako Pure Chemical Co., Ltd.) Cayman Flavonols (Manufacturer: Cayman Chemical Company) Quercetin (Manufacturer: Cayman Chemical Company) Protocyanidin A1 (Manufacturer: Extrasynthese Company) Protocyanidin B2 (Manufacturer: Cayman Chemical Company) Protocyanidin B3 (Manufacturer: Extrasynthese Company)

In the following test examples, the concentration of the raw materials of the above-mentioned commercial products is used as a standard. Suspend and dissolve 0.1 g of the powder of the above raw materials in 100 μL of PBS (phosphate buffer saline), and add 10 μL of this solution to serum-free DMEM (Dulbecco's Modified Eagle Medium; Dulbecco's Modified Eagle Medium) Dissolve in 240 μL of /F12 medium. Furthermore, 10 μL of this solution was added to 190 μL of the EMT induction medium described below and dissolved.

[Test Example 1. EMT inhibitory activity: Focus formation inhibition assay] The EMT inhibitory activity evaluation method using cells was constructed based on research conducted in International Publication No. 2017/104833. International Publication No. 2017/104833 describes that when EMT is induced in retinal pigment epithelial cells (RPE cells; retinal pigment epithelium), the formation of Focus is confirmed. The amount of Focus formation can be verified by whether or not a sample is added (using the number and volume of Focus as indicators), thereby evaluating the EMT inhibitory activity. The specific evaluation method is as follows.

RPE cells (retinal pigment epithelial cell line: ARPE-19) were seeded on a culture plate and cultured at 37°C for 5 days. Use EMT-inducing medium supplemented with TNF-α (tumor necrosis factor-α; tumor necrosis factor-α) and TGF-β (transforming growth factor-β; transforming growth factor-β) to culture RPE cells to induce EMT. At the same time, the evaluation target sample is added. As the EMT induction control group, a sample to which the evaluation target sample was not added was used. After 48 hours of EMT induction, the cells were fixed with 4% paraformaldehyde solution at room temperature for 30 minutes, and then washed three times with PBS. Treat with 0.2% Triton-X/PBS solution for 5 minutes and wash 3 times with PBS. Stain the cells with fluorescent staining solution (0.2% Phalloidin-Alexa 568 (Molecular Probes #A12380)/0.05% Hochest 33342 (Invitrogen #H3570)/3% BSA-PBS) for 1 hour at room temperature, and then proceed with PBS. 5 minutes × 3 washes. The fluorescently stained cell lines were imaged using Image Express Micro (Molecular Devices) and digitized using MetaXpress2.0 (Molecular Devices). The amount of Focus formed (Focus amount) was analyzed based on the numerical data, and the EMT inhibitory activity (inhibition rate (%)) was calculated using the following formula 1 based on the numerical value when no compound was added, and the EMT in each sample was verified. Inhibitory effect. The formation amount of Focus is calculated using the number and volume of Focus as indicators.

[Formula 1]

The IC50 (50% inhibitory concentration; half inhibitory concentration) in the table is calculated using the following formula 2. [Formula 2] A: sandwiching a high concentration of 50%. B: Sandwiched with a low concentration of 50%. C: Inhibition rate at a low concentration of 50%. D: Inhibition rate at a high concentration of 50%. As a result, the EMT inhibitory effect was confirmed for the following compounds.

[Table 1] IC50(μg/ml) Unripe apple extract 0.5 red rice extract 100-1000 Purple Tea Extract <10 Lychee extract 0.17 Acai Berry Extract 100-1000 Phyllanthus emblica extract 6.7-67 cocoa extract 6.7-67 Aronia berry extract 0.94 blackcurrant extract 1.96 Maqui Berry Extract <6,7 black bean extract 1.77 Bilberry Extract 100-1000 Cyanidin-3-glucoside (C3G) 3.98 Cyanidin chloride 2.06 delphinidin chloride 1.23 coriander 0.6 Cannon flavonols 2.73 Quercetin 3.06 Protocyanidin A1 0.76 Protocyanidin B2 1.03 Protocyanidin B3 1.08

As shown in Table 1, apple, red rice, purple tea, lychee, acai berry, amla, cocoa, aronia, black currant, maquiberry, black bean, and bilberry were confirmed as plant bases. The extract has anti-EMT activity through the action of plant-derived polyphenols. Although not limited, among these extracts, the IC50 of unripe apple extract, lychee extract, aronia extract, black currant extract, and black bean extract was 5 μg/ml or less, and significant anti-EMT was confirmed. active.

In addition, the anti-EMT activity of each plant-derived polyphenol was confirmed, and the results showed that cyanidin-3-glucoside (C3G), cyanidin, delphinidin, corianderin, kanfeflavonol, and quercetin , procyanidin A1, procyanidin B2, and procyanidin B3, significant anti-EMT activity was confirmed.

As shown in Patent Document 1 and Patent Document 2, Tranilast has the effect of inducing the leaf-like morphology between endometrial epithelial cells into an epithelial shape (EMT inhibitory activity), and is effective in functional (primary) dysmenorrhea. , patients with any type of organic (secondary) dysmenorrhea have confirmed the obvious effect of improving dysmenorrhea.

Therefore, it is speculated that the novel plant-derived polyphenols with anti-EMT activity discovered in this application can also maintain the morphological changes in the endometrial epithelial tissue to a normal state through the same effect, thereby enabling Suppress and improve the discomfort associated with menstruation.

Claims (5)

A composition for improving discomfort associated with menstruation, containing plant-derived polyphenols with anti-epithelial-mesenchymal transition (EMT) activity. The composition for improving discomfort associated with menstruation as described in claim 1, wherein the aforementioned plants are selected from the group consisting of apple, red rice, purple tea, lychee, acai berry, amla, cocoa, aronia, black At least 1 species from the group consisting of currant, maquiberry, black bean, and huckleberry. The composition for improving discomfort associated with menstruation as described in Claim 1 or 2, wherein the discomfort associated with menstruation is discomfort occurring during or before menstruation. The composition for improving the discomfort associated with menstruation as described in claim 1 or 2, wherein the discomfort associated with menstruation is selected from the group consisting of lower abdominal pain, low back pain, abdominal distension, headache, nausea, anemia, dizziness when standing, and diarrhea. , Fatigue, lethargy, depression, emotional instability, decreased concentration, drowsiness, chest swelling (breast pain), lower abdominal swelling, edema, stiff shoulders, rough skin, decreased appetite, increased appetite, decreased efficiency, At least one of the group consisting of chills or sweating, weight gain, and conditions that cause difficulties in daily life. The composition for improving discomfort associated with menstruation as described in Claim 1 or 2, which is an oral preparation.