Composition for improving discomfort associated with menstruation

Abstract

This invention provides a composition for improving menstrual discomfort that is effective for discomfort in women from menarche to menopause, especially severe discomfort in young women, and which has sufficient history of consumption and possesses anti-EMT activity, as well as a functional food containing the composition. [Solution] Prepare a composition for improving discomfort associated with menstruation, containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof.

Description

Technical Field

[0001] The present invention relates to a composition and a functional food for improving uncomfortable conditions associated with menstruation, which are recognized by many women. More specifically, the present invention relates to a functional food that is effective for young women who tend to feel strong discomfort and uneasiness even though no organic disorder is particularly recognized in the genital system.

Background Art

[0002] Uncomfortable conditions associated with menstruation cover a wide range, such as lower abdominal pain, low back pain, headache, nausea, diarrhea, abdominal fullness, depression, fatigue, or loss of appetite. Although endometriosis, uterine fibroids, or adenomyosis of the uterus are known as the causative diseases, there are not a few women who feel strong discomfort despite no particular organic disorder being recognized.

[0003] Particularly in young women who have not experienced childbirth, this tendency is strong. A state in which no organic disorder is particularly recognized in addition to such discomfort is defined as functional dysmenorrhea (Non-Patent Document 1), and it is considered a pre-disease in the sense that no causative disease is particularly recognized.

[0004] It is said that there are 8 million women with dysmenorrhea, which combines functional dysmenorrhea and organic dysmenorrhea, in Japan in 2012. Also, according to a 2019 estimate by the Ministry of Economy, Trade and Industry, the labor loss due to women's menstrual accompanying symptoms exceeds 490 billion yen annually (Non-Patent Document 2). It is no exaggeration to say that this is not only a serious discomfort related to women's menstruation but also a serious social problem.

[0005] On the other hand, while treatment methods for organic dysmenorrhea are relatively clear depending on the specific organic disorder, functional dysmenorrhea primarily involves the use of NSAIDs to alleviate the pain, which is the most common discomfort. Since NSAIDs are analgesics taken as needed when pain is felt, they naturally cannot improve the body's constitution to prevent pain. The trauma associated with this monthly pain is thought to be the cause of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), which are types of psychosomatic disorders, and it is difficult to improve PMS or PMDD with NSAIDs taken only when pain is felt. In cases of severe pain, there is also a treatment method that involves stopping menstruation, which is the root cause of the pain, with female hormones. In addition, there is a treatment that reduces menstrual pain by administering small amounts of female hormones to suppress follicular maturation and endometrial proliferation, but due to the psychological hurdles and side effects of forcibly altering the natural endocrine system with hormones, the current usage rate of female hormones is extremely low at 7.5% according to a survey of dysmenorrhea patients (Non-Patent Literature 3).

[0006] Furthermore, women's participation in society has increased dramatically in recent years, resulting in a trend towards later marriages. Dysmenorrhea can occur from menarche to menopause, but functional dysmenorrhea is said to be more severe in young women who have not given birth. With later marriages, the social problem of lost labor due to dysmenorrhea has become even greater, and there is a strong desire for a radical cure that can solve this serious problem for women and the resulting social loss.

[0007] On the other hand, the mechanisms of dysmenorrhea are being elucidated in recent years. Whether functional or organic dysmenorrhea, the fundamental mechanism is believed to be the transformation of endometrial epithelial cells (epithelial-mesenchymal transition {hereinafter abbreviated as EMT}) (Patent Documents 1 and 2). When tranilast, a drug that has been confirmed to have anti-EMT activity, was administered to patients with dysmenorrhea, a significant improvement in the NRS score for menstrual pain was observed (Patent Documents 1 and 2). Thus, there is a strong demand for improving one's constitution to be less susceptible to menstrual discomfort by ingesting safe ingredients that have anti-EMT activity and few side effects. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Patent No. 4709328 [Patent Document 2] Patent No. 5819599 [Non-patent literature]

[0009] [Non-Patent Document 1] Obstetrics and Gynecology Clinical Practice Guidelines - Outpatient Gynecology Edition 2017 [Non-Patent Document 2] Ministry of Economy, Trade and Industry, 2019: "Initiatives for Women's Health in Health Management" [Non-Patent Document 3] Bayer Yakuhin Ltd. News Release, June 1, 2018: "Survey on Awareness and Actual Conditions Regarding Endometriosis and Menstrual Management" [Overview of the project] [Problems that the invention aims to solve]

[0010] The object of the present invention is to provide a composition for improving menstrual discomfort that is effective for discomfort in women from menarche to menopause, particularly severe discomfort in young women, and which has sufficient history of consumption and anti-EMT activity, as well as a functional food containing the composition. [Means for solving the problem]

[0011] In light of the aforementioned issues, we conducted thorough research and found that certain plant-derived components exhibited significant anti-EMT activity and were effective in improving menstrual discomfort, thus completing the present invention.

[0012] In other words, the present invention provides the following compositions. Section 1. A composition for improving discomfort associated with menstruation, containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof. Section 2. The composition according to item 1, wherein the discomfort associated with menstruation is a discomfort that occurs during or before menstruation. Section 3. The composition according to claim 1 or 2, wherein the unpleasant condition associated with menstruation is at least one selected from the group consisting of lower abdominal pain, lower back pain, abdominal bloating, headache, nausea, anemia, diarrhea, fatigue, depression, emotional instability, decreased concentration, drowsiness, breast tenderness (breast pain), swelling, rough skin, decreased appetite, decreased efficiency, weight gain, and a condition that interferes with daily life. Section 4. The composition according to any one of claims 1 to 3, wherein the black rice extract is an extract of a part of black rice that includes at least one selected from the group consisting of the seed coat, aleurone layer, pericarp, germ, and endosperm. Section 5. The composition according to any one of claims 1 to 3, wherein the cherry blossom extract is a cherry blossom extract. Section 6. An oral preparation, the composition described in any of items 1 to 5. [Effects of the Invention]

[0013] The composition of the present invention contains a component having sufficient ingestion experience and anti-EMT activity, thereby being able to bring an effective improvement effect against menstrual discomfort, particularly the strong discomfort that is likely to occur in young women.

Brief Description of the Drawings

[0014] [Figure 1] Figure 1 is a graph showing the evaluation results of the EMT inhibitory activity (inhibition rate) by the extract of black rice in Test Example 1. [Figure 2] Figure 2 is a graph showing the evaluation results of the EMT inhibitory activity (inhibition rate) by the extract of cherry blossoms in Test Example 1.

Modes for Carrying Out the Invention

[0015] The composition of the present invention contains a component having anti-EMT activity as an active ingredient, and is expected to lead to a fundamental improvement in menstrual discomfort, the mechanism of which has been gradually clarified in recent years.

[0016] In this specification, the active ingredient is not particularly limited as long as it has sufficient ingestion experience and anti-EMT activity. Although not limited, such an active ingredient is preferably a material having ingestion experience in the food and beverage field and / or a component derived from such a material.

[0017] [Component having anti-EMT activity] As a component having anti-EMT activity, in this specification, at least one selected from the group consisting of black rice, cherry blossoms, and their extracts has been newly found.

[0018] (Black rice and its extract) Black rice is a variety of brown rice that contains a purplish-black pigment in at least one of its seed coat or pericarp, and has a black appearance. Known varieties of black rice include Shikuen, Kurodenen, Hunan Black Rice (registered trademark), Kuromurasaki, and Hubei Shikuen Rice. Black rice can be used as either brown rice (unpolished) or polished rice obtained by milling brown rice. From the viewpoint of significantly achieving the effects of the present invention, it is preferable to use at least one selected from the group consisting of the seed coat, pericarp, and germ of brown rice as the black rice.

[0019] The extraction method for black rice extract is not limited as long as it achieves the effects of the present invention. For example, black rice extract refers to an extract obtained by immersing the above-mentioned black rice or its pulverized product in water and / or an organic solvent and filtering off the residue, an extract from which the solvent has been removed, or a fine powder thereof, or an extract or solvent-removed product dissolved, dispersed, or diluted using a suitable solvent, and commercially available products can also be used. As an example of another extraction method, black rice extract can also be obtained after processing the black rice, such as by steaming it.

[0020] The black rice extract may be the crude extract obtained directly from black rice, a purified extract, a concentrated extract, a synthetic extract, or a commercially available product. There are no particular limitations on the method of obtaining the extract; conventional extraction methods, purification methods, concentration methods, synthesis methods, and drying / powdering methods can be employed.

[0021] The extraction solvent for the black rice extract is not limited as long as it achieves the effects of the present invention, but examples include lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropyl alcohol, and butanol; polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol; polar solvents such as water, acetone, ethyl acetate, and methyl acetate; and nonpolar solvents such as hexane and pyridine. Any one or any mixture of two of these may be used. Of these solvents, water, ethanol, 1,3-butylene glycol, propylene glycol, or a mixture thereof is preferred, and a mixture of water and ethanol (hydrated ethanol) is more preferred.

[0022] Commercially available black rice extracts that can be used include, but are not limited to, Black Rice Extract-P (manufacturer: Oryza Oil & Fat Chemical Co., Ltd.), Mixed Ancient Rice Extract (manufacturer: Satis Pharmaceutical Co., Ltd.), and Black Rice Extract (manufacturer: Access One Co., Ltd.).

[0023] The black rice extract is not limited as long as it achieves the effects of the present invention, but for example, the polyphenol content in the extract is preferably 3% by mass or more, more preferably 5% by mass or more, even more preferably 10% by mass or more, particularly preferably 12% by mass or more, and most preferably 15% by mass or more. The polyphenol content is not limited, but can be measured, for example, by the Folin-Denis method.

[0024] (Cherry blossoms and their extracts) Sakura (cherry blossom) is a general term for plants belonging to the genus Cerasus in the family Rosaceae, excluding plums, peaches, and apricots, and generally refers to those belonging to the subgenus Cerasus.

[0025] The type of cherry blossom used is not particularly limited; for example, cherry blossoms belonging to groups such as the Yamazakura group, Edohigan group, Mamezakura group, Chojizakura group, Miyamazakura group, and Shinamizakura group can be used. Furthermore, other species can also be used, without being limited to these groups. Specifically, for example, cherry blossoms (Prunus cerasus, etc.), European cherry blossoms (Prunus avium), Taiwan cherry blossoms (Prunus campanulata), Japanese cherry blossoms (Prunus cerasus), mountain cherry blossoms (Prunus jamasakura), misty cherry blossoms (Prunus leveilleana), Edohigan cherry blossoms (Prunus pendula), Chinese cherry blossoms (Prunus pseudocerasus), Oshima cherry blossoms (Prunus speciosa), misty cherry blossoms (Prunus verecunda), Mochizuki cherry blossoms (Prunus × mochizukiana), Somei Yoshino cherry blossoms (Prunus × yedoensis), double-flowered cherry blossoms (Prunus lannesiana), etc. can be used, but are not limited to these.

[0026] While there are no limitations on the type of cherry tree used, Prunus lannesiana is preferred from the viewpoint of significantly demonstrating the effects of the present invention.

[0027] The parts of the cherry tree used are not particularly limited and include leaves, stems, trunks, flowers, roots, fruits, etc., but it is preferable to use flowers or leaves, and more preferable to use flowers.

[0028] The method of extracting cherry blossom extract is not limited as long as it achieves the effects of the present invention. For example, cherry blossom extract refers to an extract obtained by immersing and extracting the above-mentioned cherry blossoms or their crushed material in water and / or an organic solvent and filtering off the residue, an extract from which the solvent has been removed, or a fine powder thereof, or an extract or solvent-removed product dissolved, dispersed, or diluted using a suitable solvent, and commercially available products can also be used. As an example of another extraction method, cherry blossom extract can also be obtained after processing the cherry blossoms, such as by steaming them.

[0029] The cherry blossom extract can be the crude extract obtained directly from cherry blossoms, a purified extract, a concentrated extract, a synthetic extract, or a commercially available product. There are no particular limitations on the method of obtaining the extract; conventional extraction methods, purification methods, concentration methods, synthesis methods, and drying / powdering methods can be employed.

[0030] The extraction solvent for the cherry blossom extract is not limited as long as it achieves the effects of the present invention, but examples include lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propanol, isopropyl alcohol, and butanol; polyhydric alcohols such as glycerin, propylene glycol, and polyethylene glycol; polar solvents such as water, acetone, ethyl acetate, and methyl acetate; and nonpolar solvents such as hexane and pyridine. Any one or any mixture of two of these may be used. Of these solvents, water, ethanol, 1,3-butylene glycol, propylene glycol, or a mixture thereof is preferred, and a mixture of water and ethanol (hydrated ethanol) is more preferred.

[0031] While not limited to commercially available cherry blossom extracts, products such as Cherry Blossom Extract-P (manufactured by Oryza Oil & Fat Chemical Co., Ltd.) and Cherry Blossom Syrup (manufactured by Oryza Oil & Fat Chemical Co., Ltd.) can be used.

[0032] The cherry blossom extract is not limited as long as it achieves the effects of the present invention, but for example, the caffeine oil glucose content in the extract is preferably 1% by mass or more, more preferably 1.5% by mass or more, and even more preferably 2% by mass or more. The caffeine oil glucose content can be measured by known methods and is not limited, but for example, it can be measured by HPLC.

[0033] The cherry blossom extract is not limited as long as it achieves the effects of the present invention, but for example, the quercetin glucoside content in the extract is preferably 0.01% by mass or more, more preferably 0.03% by mass or more, and even more preferably 0.05% by mass or more. The quercetin glucoside content can be measured by known methods and is not limited, but for example, it can be measured by HPLC.

[0034] In the composition of the present invention, the total content of the component having anti-EMT activity is appropriately set according to the type of component, the type and content of other components, the formulation form, the method of use, etc. Although not limited, for example, in the case of a solid formulation, the total content of the component having anti-EMT activity is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.01% by mass or more, particularly preferably 0.05% by mass or more, even more particularly preferably 0.1% by mass or more, and most preferably 0.5% by mass or more, based on the total amount of the composition. Also, in the case of a solid formulation, the total content of the component having anti-EMT activity is preferably 95% by mass or less, more preferably 90% by mass or less, particularly preferably 85% by mass or less, and most preferably 80% by mass or less, based on the total amount of the composition. In the case of a solid formulation, the total content of the component having anti-EMT activity is preferably 0.001 to 95% by mass, more preferably 0.005 to 90% by mass, even more preferably 0.01 to 85% by mass, and particularly preferably 0.05 to 80% by mass, based on the total amount of the composition. In this specification, when plant extracts are used, their content is calculated on a dry solids basis.

[0035] In the composition of the present invention, the total content of the component having anti-EMT activity is appropriately set according to the type of component, the type and content of other components, the formulation form, the method of use, etc. Although not limited to these, for example, in the case of a liquid formulation, the total content of the component having anti-EMT activity is preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, even more preferably 0.001% by mass or more, particularly preferably 0.005% by mass or more, even more particularly preferably 0.01% by mass or more, and most preferably 0.05% by mass or more, based on the total amount of the composition. Also, in the case of a liquid formulation, the total content of the component having anti-EMT activity is preferably 25% by mass or less, more preferably 20% by mass or less, particularly preferably 15% by mass or less, and most preferably 10% by mass or less, based on the total amount of the composition. The total content of the component having anti-EMT activity is preferably 0.0001 to 25% by mass, more preferably 0.0005 to 20% by mass, even more preferably 0.001 to 15% by mass, and particularly preferably 0.005 to 10% by mass, based on the total amount of the composition, in the case of a liquid formulation. In this specification, when plant extracts are used, their content is calculated on a dry solids basis.

[0036] In a preferred embodiment, for example, when black rice and / or its extract is included as an ingredient having anti-EMT activity, the content of black rice and / or its extract alone is preferably 0.001 to 95% by mass, more preferably 0.005 to 90% by mass, even more preferably 0.01 to 85% by mass, and particularly preferably 0.05 to 80% by mass, based on the dry solid content of the total composition in the case of a solid formulation. In the case of a liquid formulation, the content of black rice and / or its extract alone is preferably 0.0001 to 25% by mass, more preferably 0.0005 to 20% by mass, even more preferably 0.001 to 15% by mass, and particularly preferably 0.005 to 10% by mass, based on the dry solid content of the total composition.

[0037] In a preferred embodiment, for example, when cherry blossoms and / or their extracts are included as components having anti-EMT activity, the content of cherry blossoms and / or their extracts alone is preferably 0.001 to 95% by mass, more preferably 0.005 to 90% by mass, even more preferably 0.01 to 85% by mass, and particularly preferably 0.05 to 80% by mass, based on the dry solid content of the total composition in the case of a solid formulation. In the case of a liquid formulation, the content of cherry blossoms and / or their extracts alone is preferably 0.0001 to 25% by mass, more preferably 0.0005 to 20% by mass, even more preferably 0.001 to 15% by mass, and particularly preferably 0.005 to 10% by mass, based on the dry solid content of the total composition.

[0038] [Application] The composition of the present invention contains a component having anti-EMT activity as an active ingredient, and is therefore expected to lead to a fundamental improvement in menstrual discomfort, the mechanism of which has been elucidated in recent years.

[0039] As mentioned above, the mechanisms of dysmenorrhea are being elucidated in recent years. Dysmenorrhea is classified into functional (primary) dysmenorrhea and organic (secondary) dysmenorrhea.

[0040] Functional (primary) dysmenorrhea is a condition in which no organic disease is found in the pelvic region, and more than 90% of dysmenorrhea cases are functional (primary) dysmenorrhea. The mechanisms of onset for both functional and organic dysmenorrhea are not fully understood, and for this reason, no effective treatments have been found. As described in Patent Documents 1 and 2, it has been found that in healthy individuals (those without dysmenorrhea), the endometrial epithelial tissue normally changes from mesenchymal to epithelial characteristics during the transition from the low-temperature phase to the high-temperature phase of basal body temperature before ovulation, but in patients with dysmenorrhea, this change in characteristics is prolonged, and strong mesenchymal characteristics are maintained even after entering the high-temperature phase.

[0041] In a search for a drug that could normalize this phenotypic change, that is, change it from a mesenchymal-like phenotype to an epithelial-like phenotype, it was found that tranilast has the effect of inducing the mesenchymal-like phenotype of endometrial epithelial cells to an epithelial-like phenotype (anti-EMT activity). When tranilast with anti-EMT activity was administered to several patients with dysmenorrhea for a certain period of time and its effects were verified, a clear improvement in dysmenorrhea was confirmed in patients with both functional (primary) dysmenorrhea and organic (secondary) dysmenorrhea.

[0042] Based on the findings described in Patent Documents 1 and 2 above, it is possible to maintain the changes in the phenotype of endometrial epithelial tissue in a normal state if the component has anti-EMT activity, thereby suppressing and improving the discomfort associated with menstruation.

[0043] Unpleasant conditions associated with menstruation include physical or mental conditions selected from the group consisting of lower abdominal pain, lower back pain, abdominal bloating, headache, nausea, anemia, diarrhea, fatigue, depression, emotional instability, decreased concentration, drowsiness, breast tenderness (breast pain), swelling, skin problems, decreased appetite, decreased efficiency, weight gain, and conditions that interfere with daily life. In this specification, these unpleasant conditions can also be referred to as premenstrual or menstrual discomfort. It is presumed that if the endometrial epithelial tissue does not undergo normal morphological changes and these changes are prolonged, the above physical conditions will occur, and consequently, the above physical or mental conditions will also be triggered.

[0044] Conditions that interfere with daily life include decreased efficiency in household chores and work, inability to concentrate on household chores or work, reduced time available for active movement, disruption of daily routines, restlessness, decreased concentration, reduced motivation, a sedentary lifestyle, apathy, anxiety, and depression.

[0045] In this specification, "preventing or improving the discomfort associated with menstruation" means that the discomfort associated with menstruation, as exemplified, ceases to occur, is reduced, or is no longer felt as severe.

[0046] Menstrual symptoms include discomfort related to pain (lower abdominal pain, fatigue, stiff shoulders, headaches, lower back pain / heaviness), a heavy, constricting feeling in the lower abdomen, difficulty concentrating (decreased concentration, insomnia, increased mistakes), behavioral changes (tendency to stay indoors, excessive drowsiness, loss of motivation at work), fluid retention (skin problems, breakouts, swelling, weight gain, breast tenderness), and emotional instability (feeling lonely / anxious, depressed, mood swings, restlessness, irritability, and anger).

[0047] The menstrual discomfort described above can occur not only during menstruation but also before menstruation. Mild physical and mental symptoms may occur starting about one to two weeks before menstruation. When these physical and mental symptoms are severe enough to interfere with daily life, it is called premenstrual syndrome (PMS). While not limited to these cases, the composition of the present invention can improve physical and / or mental discomfort that occurs one to two weeks before menstruation.

[0048] Women who suffer from particularly heavy menstruation may experience mental stress such as mood swings, decreased motivation, and difficulty concentrating starting one to two weeks before their period. When this mental stress, which occurs one to two weeks before menstruation, is severe enough to interfere with daily life, it is called premenstrual mood disorder (PMDD). While not limited to these conditions, the composition of the present invention can improve mental stress that occurs one to two weeks before menstruation.

[0049] The composition of the present invention can be used by adding it to or mixing it with food and beverages. Alternatively, it can be used as a beverage or food on its own. Alternatively, it can be added to or blended into food and beverages that display statements related to the improvement of discomfort associated with menstruation as a functional claim, i.e., functional foods such as health foods, functional foods, foods for the sick, and foods for specified health uses.

[0050] For evaluating discomfort associated with menstruation, for example, the Menstrual Distress Questionnaire (MDQ) score (Moos, R. H, Journal of Psychosomatic Medicine, 30:853-867, 1968) can be used.

[0051] The MDQ score can be classified into two categories of evaluation factors: factors related to physical symptoms and factors related to mental symptoms. Factors related to physical symptoms include: (1) pain factors (stiff neck and shoulders, muscle pain, headache, lower abdominal pain, back pain, fatigue, body aches), (2) autonomic nervous system factors (dizziness, feeling spaced out, cold sweats, nausea, facial flushing), (3) fluid retention factors (weight gain, rough skin, breakouts, breast tenderness, edema in the abdomen, breasts, or legs), and (4) control factors. Symptoms include shortness of breath, a feeling of tightness in the chest, tinnitus, numbness in the hands and feet, blurred vision, and hazy eyesight.

[0052] Factors related to mental symptoms include (1) concentration factors (inability to sleep, forgetfulness, difficulty organizing thoughts, impaired judgment, decreased concentration, distractibility, increased mistakes, clumsy movements), (2) behavioral change factors (lack of perseverance in work, falling asleep on the job, difficulty getting out of bed, wanting to avoid social interaction, becoming a homebody, decreased work efficiency), (3) negative emotional factors (wanting to cry over minor things, feeling lonely, feeling anxious, restless, irritable, quick-tempered, mood swings, easily agitated, feeling depressed, easily stressed), and (4) mood-enhancing factors (feeling kind, being honest, feeling excited, feeling fulfilled, becoming active).

[0053] Methods for evaluating menstrual pain include, for example, (1) scoring subjective findings and (2) taking objective findings, as described in the guidelines of the Japanese Society for Palliative Medicine.

[0054] In the guidelines of the Japanese Society for Palliative Medicine, (1) above, the intensity of pain (subjective findings) felt by the patient is divided into 11 levels from 0 (no pain at all) to 10 (pain so severe that the patient had to take time off work (stayed in bed)) in the lower abdomen, lower back, etc., and scored as the "Numerical Rating Scale (NRS)". In addition, (2) above, the extent to which the pain interferes with daily life is evaluated through monthly interviews with a doctor.

[0055] While not limited to this, for example, if a subject is given an ingredient with anti-EMT activity and an improvement is observed in at least one of the above evaluation items, that ingredient can be evaluated as effective for that evaluation item.

[0056] Furthermore, although not limited to this, it is also possible to use PMS Memory (published by the Japan Family Planning Association) or similar tools to record daily conditions when evaluating discomfort associated with menstruation. PMS Memory is not limited to diagnosing PMS, but is also used to record women's health. For example, when using PMS Memory, it is possible to record the date, menstrual cycle, menstrual flow, basal weight, basal body temperature, symptoms and their severity, and other events.

[0057] In addition to the above, scales that evaluate quality of life (QOL) can also be used to assess discomfort associated with menstruation. Examples of such scales include the SF-36, a Health-related QOL (HR-QOL) scale, as well as its shortened versions, the SF-12v2, SF-8, and the EQ-5D-5L.

[0058] The SF-36 is an assessment scale that evaluates individuals by having them answer questions on eight subscales (items): (1) physical functioning, (2) role functioning (physical), (3) physical pain, (4) overall health perception, (5) vitality, (6) social functioning, (7) role functioning (mental), and (8) mental health.

[0059] The EQ-5D-5L is a questionnaire developed by the EuroQOL Group, in which respondents answer on a 5-point scale for five items: "Degree of mobility," "Self-care," "Daily activities," "Pain and discomfort," and "Anxiety and depression."

[0060] [Dosage form] Health foods, functional foods, foods for the sick, and foods for specified health uses can be used in various formulations, such as solid preparations (tablets, granules, fine granules, powders, capsules, chewable tablets, etc.), liquid preparations (drinks, syrups, suspensions), and liquid foods. Foods in formulation form can be manufactured in the same way as known pharmaceutical preparations, by mixing the active ingredient with a food-acceptable carrier, such as a suitable excipient, and then manufacturing it using conventional methods.

[0061] For example, tablets can be prepared by mixing a powdered active ingredient with a pharmaceutically acceptable carrier component (such as an excipient) and then compression molding, while confectionery tablets such as candies may be prepared by injecting the mixture into a mold. Tablets may also be coated with sugar to form sugar-coated tablets. Furthermore, tablets may be single-layer tablets or laminated tablets such as double-layer tablets.

[0062] Granules and other powdered materials may be prepared by various granulation methods (extrusion granulation, crushing granulation, dry compaction granulation, fluid bed granulation, rolling granulation, high-speed stirring granulation, etc.), and tablets can be prepared by appropriately combining the above granulation methods and tableting methods (wet tableting, direct tableting, etc.).

[0063] Capsules can be prepared by conventional methods, which involve filling capsules (soft or hard capsules) with powders or granules.

[0064] Liquid formulations can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, ethanol-containing purified water, etc.) which is a carrier component, filtering or sterilizing as necessary, filling into a predetermined container, and sterilizing again. The preferred dosage form of the solid formulation of the present invention is a capsule or a tablet, and more preferably a soft capsule (soft capsule).

[0065] Soft capsules are preferred by users because their smooth surface makes them easy to swallow. Common methods for manufacturing soft capsules include the plate method, the rotary method, and the seamless method.

[0066] In rotary (punching) manufacturing, a sheet-like capsule coating sandwiches the flowing filling material and forms a capsule shape along the holes of a rotating cylindrical mold. On the other hand, in seamless (dropping) manufacturing, the capsule coating composition and the contents are simultaneously discharged from multiple concentric nozzles, forming a seamless capsule shape.

[0067] The base material for the capsule coating is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinylated gelatin, etc., can be used, with starch, gelatin, and succinylated gelatin being preferred, and gelatin and succinylated gelatin being even more preferred. These may be used individually or in combination of two or more.

[0068] Furthermore, food compositions can be manufactured as soups, juices, fruit juices, milk, dairy beverages, whey beverages, lactic acid bacteria beverages, tea beverages, herbal teas and other black teas, alcoholic beverages, coffee beverages, carbonated beverages, soft drinks, water beverages, cocoa beverages, jelly beverages, sports drinks, diet drinks and other liquid beverages, semi-solid foods such as puddings and yogurts, noodles, confectionery, spreads, and the like.

[0069] Food compositions may contain various food additives. Examples of food additives include antioxidants, colorants, flavorings, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, and preservatives.

[0070] When preparing a pharmaceutical composition according to the present invention, it is prepared as a formulation comprising an active ingredient having anti-EMT activity and, preferably, a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid filler, diluent, or encapsulating material that does not react with the active ingredient, and examples include water, ethanol, polyols, suitable mixtures thereof, solvents or dispersion media such as vegetable oils.

[0071] Pharmaceutical compositions are administered orally or parenterally, for example, into the oral cavity, gastrointestinal tract, or nasal cavity. Oral formulations include solid formulations (tablets, granules, fine granules, powders, capsules, chewable tablets, etc.) and liquid formulations (syrups, suspensions, inhalants, etc.). Parenteral formulations include intravenous infusions, nasal drops, and injections.

[0072] The pharmaceutical composition may further contain additives commonly used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, colorants, and flavoring agents, and can be used as appropriate. To enable sustained release for longer-lasting action, it may also be coated with known retarders, etc. The pharmaceutical composition may further contain other additives or drugs, such as antacids and gastric mucosal protectants, as needed.

[0073] Pharmaceutical compositions can be applied in forms such as oral compositions and internally administered compositions. Furthermore, pharmaceutical compositions may be used therapeutically or non-therapeutically.

[0074] The daily oral intake or dosage of an adult component having anti-EMT activity can be appropriately determined based on the individual's condition, weight, sex, age, activity of the material, route of intake or administration, intake or administration schedule, formulation, or other factors.

[0075] The daily oral intake or dosage of black rice or its extract for adults is preferably, for example, 0.001 mg / kg body weight / day or more, more preferably 0.005 mg / kg body weight / day or more, even more preferably 0.01 mg / kg body weight / day or more, particularly preferably 0.05 mg / kg body weight / day or more, and most preferably 0.1 mg / kg body weight / day or more. The daily oral intake or dosage of black rice or its extract for adults is preferably, for example, 2000 mg / kg body weight / day or less, more preferably 1500 mg / kg body weight / day or less, even more preferably 1000 mg / kg body weight / day or less, particularly preferably 800 mg / kg body weight / day or less, and most preferably 500 mg / kg body weight / day or less. The daily oral intake or dosage of black rice or its extract for adults is preferably, for example, 0.001 to 2000 mg / kg body weight / day, more preferably 0.005 to 1500 mg / kg body weight / day, even more preferably 0.01 to 1000 mg / kg body weight / day, particularly preferably 0.05 to 800 mg / kg body weight / day, and most preferably 0.1 to 500 mg / kg body weight / day. The content of black rice or its extract can be set to the amount of the above intake or dosage. The daily oral intake or dosage for adults may be divided according to the dosage form; for example, if it is a capsule, it may be taken in the form of 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules.

[0076] [Applicable persons] When the present invention is used in the food and beverage field, such as functional foods, there are no limitations, but the target users may be, for example, those who experience discomfort associated with menstruation. Alternatively, the target users may also be, for example, those who have not been diagnosed with dysmenorrhea, those who do not undergo continuous medical treatment for menstrual-related issues, or those who do not receive continuous prescriptions for medication due to discomfort associated with menstruation. Individuals who do not experience any particular discomfort except during or before menstruation can be said to be in a pre-disease state.

[0077] Furthermore, although not limited, eligible individuals may also be those who have been ruled out of organic dysmenorrhea based on the results of a medical interview and examination by a physician. The exclusion of organic dysmenorrhea can be achieved by determining that there are no abnormalities in at least one of the following tests selected from the group consisting of internal examination, ultrasound examination, peripheral blood test, CRP test, bacterial culture test, Chlamydia antigen test, and imaging diagnosis.

[0078] Furthermore, discomfort associated with menstruation tends to be more pronounced in young women. Therefore, the composition of the present invention may be used in adolescence (around 10 to 18 years old), young adulthood (around 15 to 30 years old), or even in people 15 years of age or older, or in middle-aged individuals (around 45 years of age or older but under 55 years of age).

[0079] The present invention may also be in the following embodiments. A composition for improving discomfort associated with menstruation, containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof; A composition containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof, for use in improving discomfort associated with menstruation; Use of a composition containing black rice, cherry blossoms, and at least one selected from the group consisting of extracts thereof, for the manufacture of an agent for improving discomfort associated with menstruation; A method for improving menstrual discomfort, comprising administering to a person a composition containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof; The composition, use, or method described above, wherein the discomfort associated with menstruation is a discomfort that occurs during or before menstruation; The composition, use, or method described above, wherein the unpleasant condition associated with menstruation is at least one selected from the group consisting of lower abdominal pain, lower back pain, abdominal bloating, headache, nausea, anemia, diarrhea, fatigue, depression, emotional instability, decreased concentration, drowsiness, breast tenderness (breast pain), edema, skin problems, decreased appetite, decreased efficiency, weight gain, and conditions that interfere with daily life; The composition, use, or method described above, wherein the unpleasant condition occurring before menstruation is premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD); The composition, use, or method described above, wherein the premenstrual discomfort is a physical and / or mental discomfort occurring one to two weeks prior to menstruation; A composition for improving dysmenorrhea, containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof; A composition containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof, for use in improving dysmenorrhea; Use of a composition containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof, for the manufacture of an agent for improving dysmenorrhea; A method for improving dysmenorrhea, comprising administering to a person a composition containing at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof; The composition, use, or method described above, wherein the dysmenorrhea is functional (primary) dysmenorrhea or organic (secondary) dysmenorrhea; The composition, use, or method described above, wherein the black rice is a variety that contains a purplish-black pigment in at least one of the seed coat or pericarp of brown rice; The composition, use, or method described above, wherein the aforementioned black rice comprises at least one selected from the group consisting of Shikuen, Kurodenen, Hunan Black Rice (registered trademark), Hei Shi, and Hubei Purple Black Rice; The composition, use, or method described above, wherein the black rice extract is an extract of a part of black rice that includes at least one selected from the group consisting of the seed coat, aleurone layer, pericarp, germ, and endosperm; The composition, use, or method described above, wherein the polyphenol content in the black rice extract is 3% by mass or more; The composition, use, or method described above, wherein the polyphenol content in the black rice extract is 10% by mass or more; The composition, use, or method described above, wherein the polyphenol content in the black rice extract is 15% by mass or more; The above composition, use, or method, wherein the cherry blossom is a variety belonging to the subgenus Cerasus; The composition, use, or method described above, wherein the aforementioned cherry blossom includes at least one species selected from the group consisting of sakura (cherry) (Prunus cerasus, etc.), European sweet cherry (Prunus avium), Taiwan cherry (Prunus campanulata), Sumi cherry (Prunus cerasus), mountain cherry (Prunus jamasakura), Kasumi cherry (Prunus leveilleana), Edohigan cherry (Prunus pendula), Chinese sweet cherry (Prunus pseudocerasus), Oshima cherry (Prunus speciosa), Kasumi cherry (Prunus verecunda), Mochizuki cherry (Prunus × mochizukiana), Somei Yoshino cherry (Prunus × yedoensis), and Yaezakura (Prunus lannesiana); The above composition, use, or method, wherein the cherry blossoms include double-flowered cherry blossoms (Prunus lannesiana); The composition, use, or method described above, wherein the cherry blossom extract is an extract of a part of the cherry tree that includes at least one selected from the group consisting of leaves, stems, trunks, flowers, roots, and fruits; The composition, use, or method described above, wherein the content of caffeine oil glucose in the cherry blossom extract is 1% by mass or more; The composition, use, or method described above, wherein the content of caffeine oil glucose in the cherry blossom extract is 1.5% by mass or more; The composition, use, or method described above, wherein the content of caffeine oil glucose in the cherry blossom extract is 2% by mass or more; The composition, use, or method described above, wherein the cherry blossom extract contains 0.01% by mass or more of quercetin glucoside; The above composition, use, or method wherein the content of quercetin glucoside in the cherry blossom extract is 0.1% by mass or more; The composition, use, or method described above, wherein the cherry blossom extract contains 1% by mass or more of quercetin glucoside; In the case of a solid preparation, the composition, use, or method described above, wherein the content of at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.001 to 95% by mass; In the case of a solid preparation, the composition, use, or method described above, wherein the content of at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.05 to 80% by mass; In the case of a liquid preparation, the composition, use, or method described above, wherein the content of at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.0001 to 25% by mass; In the case of a liquid preparation, the composition, use, or method described above, wherein the content of at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.005 to 10% by mass; The above composition, use, or method, which is an oral preparation; The above-mentioned composition, use, or method, which is a solid dosage form (e.g., tablets, granules, fine granules, powders, capsules, chewable tablets) or a liquid dosage form (e.g., a drink, syrup, suspension); The composition, use, or method described above, wherein the daily oral intake of at least one substance selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.001 to 2000 mg / kg body weight / day for adults; The composition, use, or method described above, wherein the daily oral intake of at least one substance selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.01 to 1000 mg / kg body weight / day for an adult; The composition, use, or method described above, wherein the daily oral intake of at least one substance selected from the group consisting of black rice, cherry blossoms, and extracts thereof is 0.1 to 500 mg / kg body weight / day for an adult; The above composition, use, or method of application (ingestion) may be for adolescents (around 10 to 18 years old), young adults (around 15 to 30 years old), or those 15 years of age or older, or middle-aged individuals (around 45 years of age or older but under 55 years of age). [Examples]

[0080] Next, the present invention will be specifically described with reference to examples and test cases, but the present invention is not limited to the following examples and test cases.

[0081] As the black rice extract, we used Black Rice Extract-P (manufacturer: Oryza Oil & Fat Chemical Co., Ltd.). This extract is made from the seeds of black rice (Oryza sativa Linne (Gramineae)) and extracted using aqueous ethanol. The polyphenol content in the extract is 15% by mass or more.

[0082] As the cherry blossom extract, we used Cherry Blossom Extract-P (manufacturer: Oryza Oil & Fat Chemical Co., Ltd.). This extract is made from the flowers of the Rosaceae family cherry tree (Prunus Lannesiana) and extracted using aqueous ethanol. The extract contains 2% by mass or more of quercetin glucoside.

[0083] In the following test example, the concentration of the raw material extract of the commercially available product mentioned above is used as the standard. 0.1 g of the powder of the above raw material is suspended and dissolved in 100 μL of PBS, and 10 μL of this solution is added and dissolved in 240 μL of Serum-free DMEM / F12 medium. Another 10 μL of this solution is added and dissolved in 190 μL of EMT induction medium as described below. This is used as the 0.2% (W / V) sample, and further dilutions of this sample 10-fold and 100-fold with EMT induction medium are used as the 0.02% (W / V) and 0.002% (W / V) samples, respectively.

[0084] (Test Example 1. EMT Inhibitory Activity: Focus Formation Inhibition Assay Method) A method for evaluating EMT inhibitory activity using cells has been investigated and developed in International Publication No. 2017 / 104833. International Publication No. 2017 / 104833 describes that when EMT is induced in retinal pigment epithelial cells (RPE cells), the formation of Focus can be confirmed. By verifying the amount of Focus formation (using the number and volume of Focus as indicators) with and without the addition of the extract, it is possible to evaluate the EMT inhibitory activity. The specific evaluation method is as follows:

[0085] RPE cells (retinal pigment epithelial cell line: ARPE-19) were seeded on plates and incubated at 37°C for 5 days. EMT was induced in RPE cells by culturing them in EMT induction medium supplemented with TNF-α and TGF-β, and the target extract was added simultaneously. A sample without the target extract was used as an EMT induction control. 48 hours after EMT induction, cells were fixed by treatment with 4% paraformaldehyde solution at room temperature for 30 minutes, and then washed three times with PBS. They were treated with 0.2% Triton-X / PBS solution for 5 minutes and washed three times with PBS. Fluorescent staining solution (0.2% Phalloidin-Alexa 568 (Molecular Probes, Inc. #A12380) / 0.05% Hochest) was used. Cells were stained with 33342 (Invitrogen #H3570) / 3% BSA-PBS at room temperature for 1 hour, and then washed with PBS three times for 5 minutes each. The fluorescently stained cells were imaged using Image Express Micro (Molecular Devices) and quantified using MetaXpress 2.0 (Molecular Devices). By analyzing the amount of focus formation (Focus amount) from the numerical data, the EMT inhibitory activity (inhibition rate (%)) was calculated using Equation 1 below, with the value without compound addition as the baseline, to verify the EMT inhibitory effect of each extract. The amount of focus formation was determined using the number and volume of focus as indicators. After acquiring the fluorescence images, the cells were treated with 100% methanol at room temperature for 10 minutes twice to observe the overall image at low magnification, and then stained with Giemsa stain (Nacalai Tesque #37114-35) at room temperature for 15 minutes. After washing three times with methanol, the cells were dried at room temperature for 3 hours. The dried cells were observed under a microscope.

[0086] (Formula 1) JPEG2026048911000002.jpg32169

[0087] Figure 1 shows the evaluation results of EMT inhibitory activity (inhibition rate (%)) using black rice extract, and Figure 2 shows the results using cherry blossom extract.

[0088] As shown in Figure 1, the black rice extract retained 100% of its EMT inhibitory activity even at a dilution ratio of 1 / 100 (0.002% sample).

[0089] As shown in Figure 2, the cherry blossom extract retained 100% of its EMT inhibitory activity even at a dilution ratio of one-tenth of the original extract (0.02% sample).

[0090] As shown in Patent Documents 1 and 2, tranilast has the effect of inducing the mesenchymal phenotype of endometrial epithelial cells to become epithelial (EMT inhibitory activity), and a clear improvement in dysmenorrhea has been confirmed in patients with both functional (primary) dysmenorrhea and organic (secondary) dysmenorrhea.

[0091] Therefore, it is presumed that the novel anti-EMT activity component discovered in this application can similarly maintain the changes in phenotype of endometrial epithelial tissue in a normal state, thereby suppressing and improving the discomfort associated with menstruation.

Claims

1. It contains at least one selected from the group consisting of black rice, cherry blossoms, and extracts thereof. (i) If the composition contains a black rice extract, the black rice extract is an aqueous ethanol extract, and the polyphenol content in the black rice extract is 15% by weight or more, (ii) If the composition contains a cherry blossom extract, the cherry blossom extract is an aqueous ethanol extract derived from cherry blossoms, The cherry blossom extract contains 1% by weight or more of caffeoyl glucose and / or 0.01% by weight or more of quercetin glycoside. Oral composition for improving discomfort associated with menstruation.

2. The oral composition according to claim 1, wherein the unpleasant state associated with menstruation is an unpleasant state that occurs during or before menstruation.

3. The oral composition according to claim 1 or 2, wherein the unpleasant condition associated with menstruation is at least one selected from the group consisting of lower abdominal pain, lower back pain, abdominal bloating, headache, nausea, anemia, diarrhea, fatigue, depression, emotional instability, decreased concentration, drowsiness, breast tenderness (breast pain), swelling, rough skin, decreased appetite, decreased efficiency, weight gain, and a condition that interferes with daily life.

4. The oral composition according to any one of claims 1 to 3, wherein the black rice extract is an extract of a part of black rice that includes at least one selected from the group consisting of the seed coat, aleurone layer, pericarp, germ, and endosperm.

5. The daily oral intake for an adult of at least one substance selected from the group consisting of the aforementioned black rice, cherry blossoms, and extracts thereof is 0.001 to 2000 mg / kg body weight / day. An oral composition according to any one of claims 1 to 4.

6. A pharmaceutical composition comprising the oral composition described in any one of claims 1 to 5.

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