Composition for maintaining and / or improving immune function

Abstract

To provide a composition that can maintain and / or improve immune function. [Solution] A composition for maintaining and / or improving immune function, containing vitamin B6 and at least one selected from iron, zinc, and vitamin B1. Preferably, the composition contains vitamin B6, vitamin B1, and one or more selected from iron and zinc. Preferably, the composition is intended to improve health problems associated with symptoms specific to women, selected from menstruation, childbirth, infertility, and menopause.

Description

Technical Field

[0001] The present invention relates to a composition for maintaining and / or improving immune function.

Background Art

[0002] Innate immunity is one of the immune mechanisms possessed by the human body. Innate immunity is a defense mechanism that rapidly eliminates foreign substances (bacteria, viruses, cancer cells) in the living body without relying on antibodies, and pathogens such as bacteria and viruses that have entered the body, as well as foreign substances such as pollen, are attacked and destroyed by natural killer (NK) cells and the like. Natural killer (NK) cells are also known to secrete IFN-γ to promote the differentiation of type 1 helper T (Th1) cells, induce the release of cytokines, activate cells such as B cells, killer T cells, NK cells, and macrophages, and phagocytose bacteria and viruses to destroy them using phagocytosis and digestive enzymes. In innate immunity, enhanced expression of IFN-γ in NK cells is important.

[0003] Meanwhile, women experience symptoms specific to women throughout their life cycle. Specifically, physical and mental discomfort symptoms caused by menstruation (such as premenstrual syndrome "PMS", premenstrual dysphoric disorder "PMDD", etc.), infertility, physical and mental discomfort symptoms caused by pregnancy (fever, abdominal pain, diarrhea, emotional instability, postpartum depression, etc.), and physical and mental discomfort symptoms caused by menopause (joint pain, muscle pain, eczema, malaise, irritability, etc.) appear in women.

[0004] It is known that the deterioration of the above-mentioned symptoms specific to women is related to immunity. For example, it is known that premenstrual syndrome "PMS" is exacerbated by a decrease in immunity. Therefore, in order to improve symptoms specific to women, it is important to maintain and / or improve immune function.

[0005] Vitamin B6 is known to be involved in the activation of immune cells and to maintain immune function. Therefore, in order to maintain or improve immune function, combinations of vitamin B6 with various components have been investigated.

[0006] For example, Patent Document 1 describes a composition containing IL-1β and vitamin B6 for enhancing the immunomodulatory and inflammatory modulatory abilities of stem cells. According to Patent Document 1, using the composition described in the document increases the secretion of IFN-γ.

[0007] Furthermore, Patent Document 2 describes a composition containing oleuropein and / or its metabolites and vitamin B6. According to Patent Document 1, immune function is maintained by using the composition described in that document. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] Special Publication No. 2023-510291 [Patent Document 2] Special Publication No. 2024-508402 [Overview of the Initiative] [Problems that the invention aims to solve]

[0009] However, the methods described in Patent Documents 1 and 2 did not adequately maintain and / or improve immune function. Therefore, there was a need for a composition that could improve the function of maintaining and / or improving immune function. [Means for solving the problem]

[0010] The inventors diligently conducted research to solve the aforementioned problems. As a result, they discovered that the aforementioned problems can be solved by combining vitamin B6 with a specific vitamin or a specific mineral.

[0011] The present invention provides the following: [1] Vitamin B6 and, A composition for maintaining and / or improving immune function, containing at least one selected from iron, zinc, and vitamin B1. [2] Vitamin B6 and, A composition for maintaining and / or improving immune function, containing at least one selected from iron and zinc. [3] Vitamin B6, Vitamin B1, It contains at least one selected from iron and zinc. , compositions for maintaining and / or improving immune function. [4] Vitamin B6, Vitamin B1, Iron and A composition containing zinc for maintaining / improving immune function. [5] A composition for maintaining and / or improving immune function according to any one of [1] to [4], comprising 0.5 to 20 parts by mass of iron as an iron compound per 1 part by mass of vitamin B6. [6] A composition for maintaining and / or improving immune function according to any one of [1] to [5], comprising 0.5 to 20 parts by mass of zinc as a zinc compound per 1 part by mass of vitamin B6. [7] A composition for maintaining and / or improving immune function according to any one of [1] to [6], wherein the composition contains 0.1 to 5 parts by mass of vitamin B1 per 1 part by mass of vitamin B6. [8] A composition for maintaining and / or improving immune function according to any one of [1] to [7], wherein the total content of the vitamin B6 and the vitamin B1 is 1 part by mass, and the total content of the iron and the zinc as a compound is 0.5 to 20 parts by mass. [9] Furthermore, a composition for maintaining and / or improving immune function according to any one of items [1] to [8], comprising at least one component selected from the group consisting of (a) to (c) below. (a) At least one beneficial bacterium selected from lactic acid bacteria, bifidobacteria, and butyrate-producing bacteria. (b) at least one saccharide selected from glucose, fructooligosaccharides and reduced maltose syrup. (c) at least one additive selected from folic acid, selenium and resveratrol. 〔10〕 The composition for maintaining and / or improving immune function according to any one of claims 1 to 9, characterized in that it is intended for female subjects. 〔11〕 The composition for maintaining and / or improving immune function according to any one of claims 1 to 10, which is intended to ameliorate poor health associated with female-specific symptoms selected from menstruation, childbirth, infertility and menopause. Effects of the Invention

[0012] According to the present invention, a composition capable of maintaining and / or improving immune function is provided. Modes for Carrying Out the Invention

[0013] Hereinafter, the present invention will be described based on preferred embodiments thereof. The composition of the present invention is used for maintaining and / or improving immune function. As used in the present invention, "maintaining immune function" refers to suppressing a decline in immune function. Improving immune function means further enhancing immune function.

[0014] The composition of the present invention contains vitamin B6 and at least one selected from iron, zinc and vitamin B1. By combining vitamin B6 with iron, zinc or vitamin B1, a function of maintaining and / or improving immune function that exceeds the function of each component is exhibited. Even if vitamin B6 is combined with vitamins other than vitamin B1 (for example, vitamin D), the effects of the present invention cannot be achieved. Furthermore, even if vitamin B6 is combined with minerals other than iron and zinc (for example, selenium), the effects of the present invention cannot be achieved. Although the mechanism by which the effects of the present invention are exhibited is not clear, the present inventors have found that by combining vitamin B6 with specific other components, the enhancement of IFN-γ expression can be dramatically improved, which may lead to a dramatic improvement in macrophage activation capacity.

[0015] Examples of vitamin B6 include pyridoxal, pyridoxine, and pyridoxamine. These may also be in the form of salts; for example, pyridoxine may be in the form of a salt, such as hydrochloride, sulfate, nitrate, hydrobromide, or phosphate. Pyridoxal may also be a phosphate ester. In this invention, it is particularly preferable to include pyridoxine or a salt thereof as vitamin B6, due to its excellent effect in maintaining and improving immune function, and among these, it is preferable to include pyridoxine hydrochloride.

[0016] In the composition of the present invention, the term "iron" is not particularly limited as long as it is an edible compound containing iron. Examples include ferric chloride, sodium iron chlorophyllin, ferric citrate, and ferric pyrophosphate, and one or more selected from these can be used. These may be hydrated or anhydrous. The proportion of iron element in the iron compound is preferably 3 to 90% by mass, more preferably 5 to 70% by mass, and particularly preferably 6 to 40% by mass. In particular, in the present invention, ferric chloride is preferred, and ferric(II) chloride is particularly preferred, due to its excellent effect in maintaining and improving immune function. In this specification, "iron content" refers to the content of iron as a compound.

[0017] In the composition of the present invention, the term "zinc" is not particularly limited as long as it is a zinc-containing, edible compound. Examples include zinc chloride, zinc sulfate, zinc gluconate, zinc lactate, and zinc citrate, and one or more selected from these can be used. The proportion of zinc element in the zinc compound is preferably 3 to 90% by mass, more preferably 5 to 70% by mass, and particularly preferably 10 to 55% by mass. In particular, in the present invention, zinc gluconate is preferred because of its excellent effect in maintaining and improving immune function. In this specification, "zinc content" refers to the content of zinc as a compound.

[0018] The vitamin B1 in the composition of the present invention comprises thiamine or its salts or derivatives. Examples of thiamine salts include thiamine hydrochloride and thiamine nitrate. Examples of thiamine derivatives include thiamine monophosphate, thiamine diphosphate, thiamine triphosphate, octothiamine, shikothiamine, thiamine disulfide, thiamine dicetyl sulfate, bisthiamine nitrate, dicetiamine hydrochloride, fursultiamine hydrochloride, allithiamine, bisibthiamine, bisbentiamine, fursultiamine, prosultiamine, and benfotiamine. In this invention, it is particularly preferable to include thiamine or a salt thereof as vitamin B1, due to its excellent effect in maintaining and improving immune function, and among these, it is preferable to include thiamine hydrochloride.

[0019] From the viewpoint of further enhancing the effect of maintaining and improving immune function, the composition of the present invention preferably contains vitamin B6 and one or more selected from iron and zinc, more preferably contains vitamin B6, vitamin B1 and one or more selected from iron and zinc, and most preferably contains all of vitamin B6, vitamin B1, iron and zinc.

[0020] When the composition of the present invention contains iron, the amount of iron per 1 part by mass of vitamin B6 is preferably, for example, 0.5 parts by mass or more, more preferably 1 part by mass or more, even more preferably 1.5 parts by mass or more, most preferably 2 parts by mass or more, even more preferably 4 parts by mass or more, and especially preferably 8 parts by mass or more. Furthermore, the amount of iron per 1 part by mass of vitamin B1 is preferably 20 parts by mass or less, from the viewpoint of excellent effect in maintaining and improving immune function, more preferably 15 parts by mass or less, and even more preferably 10 parts by mass or less.

[0021] Furthermore, in order to be even more effective in maintaining and improving immune function, when the composition of the present invention contains zinc, the amount of zinc per 1 part by mass of vitamin B6 is preferably, for example, 0.5 parts by mass or more, more preferably 0.6 parts by mass or more, even more preferably 1 part by mass or more, even more preferably 1.5 parts by mass or more, among which preferably 2 parts by mass or more, particularly preferably 4 parts by mass or more, and especially preferably 8 parts by mass or more. Also, the amount of zinc per 1 part by mass of vitamin B1 is preferably 20 parts by mass or less in order to be even more effective in maintaining and improving immune function, more preferably 15 parts by mass or less, and even more preferably 10 parts by mass or less.

[0022] The composition of the present invention preferably contains 0.1 parts by mass or more of vitamin B1 per 1 part by mass of vitamin B6, more preferably 0.4 parts by mass or more, and even more preferably 0.7 parts by mass or more. Furthermore, it is preferable to contain 5 parts by mass or less of vitamin B1 per 1 part by mass of vitamin B6, more preferably 3 parts by mass or less, even more preferably 2 parts by mass or more, particularly preferably 1.5 parts by mass or less, and most preferably 1 part by mass or less.

[0023] When the composition of the present invention contains vitamin B6 and vitamin B1, and also contains one or more selected from iron and zinc, the total amount of iron and zinc per 1 part by mass of the total of vitamin B6 and vitamin B1 is, for example, 0.5 parts by mass or more. In particular, from the viewpoint of excellent effects in maintaining and improving immune function, it is preferable that the total amount of iron and zinc be 1 part by mass or more, more preferably 1.5 parts by mass or more, even more preferably 4 parts by mass or more, even more preferably 6 parts by mass or more, and especially preferably 7 parts by mass or more. Furthermore, when the composition of the present invention contains one or more selected from iron and zinc, the total amount of iron and zinc per 1 part by mass of the total of vitamin B6 and vitamin B1 is, for example, 20 parts by mass or less. However, it is more preferable that it be 15 parts by mass or less, and even more preferably 10 parts by mass or less, from the viewpoint of excellent effects in maintaining and improving immune function.

[0024] In this invention, it is preferable that the water-soluble vitamins contain a high proportion of vitamins B1 and B6, as this is superior in terms of maintaining and improving immune function. Examples of water-soluble vitamins include vitamins B and C. Specifically, in this invention, it is preferable that the total amount of vitamins B1 and B6 in the water-soluble vitamins is 1% by mass or more and 90% by mass or less, more preferably 10% by mass or more, and particularly preferable 30% by mass or more. In particular, in this invention, it is preferable that the proportion of vitamin B6 in the total vitamin B content is 10% by mass or more, more preferably 30% by mass or more, and particularly preferable 50% by mass or more.

[0025] In this invention, a high proportion of iron and zinc in the minerals is preferable because it is superior in maintaining and improving immune function. In this specification, minerals refer to metals with a valency of 2 or higher, and in addition to iron and zinc, include calcium, copper, magnesium, manganese, selenium, chromium, and molybdenum. This is preferable because it is superior in maintaining and improving immune function. In this invention, the total amount of iron and zinc in the minerals is preferably 10% by mass or more, more preferably 30% by mass or more, and particularly preferably 50% by mass or more. In particular, in this invention, the total amount of iron and zinc in the total amount of iron, zinc, copper, manganese, selenium, chromium, and molybdenum is preferably 10% by mass or more, more preferably 30% by mass or more, and particularly preferably 50% by mass or more. The amount of minerals referred to here is the amount based on the compound.

[0026] In the composition of the present invention, in terms of its excellent effect in maintaining and improving immune function, the proportion of vitamin B6 in the solid content of the composition is preferably 0.5% by mass or more, more preferably 1% by mass or more, and even more preferably 5% by mass or more. The proportion of vitamin B6 in the solid content of the composition is preferably, for example, 70% by mass or less, more preferably 40% by mass or less, even more preferably 20% by mass or less, and particularly preferably 10% by mass or less. The solid content refers to the amount of the composition if it is in a solid form such as a powder, and to the amount excluding the liquid medium if it is in a liquid or fluid form. Examples of liquid mediums include water and ethanol.

[0027] The composition of the present invention preferably contains, in addition to vitamin B6, vitamin B1, iron, and zinc, at least one component selected from the group consisting of (a) beneficial bacteria, (b) sugars, and (c) folic acid, selenium, and resveratrol (hereinafter referred to as the "third component"). Including these further enhances the effect of the present invention on maintaining and improving immune function. The components of the third component will be described below.

[0028] (a) beneficial bacteria In the present invention, from the viewpoint of further enhancing the effects of the present invention, it is preferable that the beneficial bacteria are at least one selected from lactic acid bacteria, bifidobacteria, and butyrate-producing bacteria.

[0029] Examples of lactic acid bacteria include those belonging to the genera Lactococcus, Enterococcus, Lactobacillus, Streptococcus, Leuconostoc, Pediococcus, Staphylococcus, Tetragenococcus, and Bacillus. One of these species may be used alone, or two or more may be used in combination.

[0030] As the Lactococcus genus, Lactococcus lactis, Lactococcus chungangensis, Lactococcus garvieae, Lactococcus piscium, Lactococcus plantarum, Lactococcus raffinolactis, etc. can be used.

[0031] Examples of species belonging to the genus Enterococcus include Enterococcus faecalis and Enterococcus faesium. Examples of species belonging to the genus Streptococcus include Streptococcus thermophilus.

[0032] Lactobacillus genus includes Lactobacillus brevis, Lactobacillus gasseri, Lactobacillus acidophilus, Lactobacillus buchneri, Lactobacillus bulgaricus, Lactobacillus delburvecki, Lactobacillus casei, Lactobacillus crispatus, Lactobacillus curvatus, Lactobacillus halivaticus, Lactobacillus pentosus, Lactobacillus plantarum (sometimes written as Lactiplantibacillus plantarum), Lactobacillus paracasei (sometimes written as Lacticaseibacillus paracasei), Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, Lactobacillus sakei, Lactobacillus Lactobacillus fructivorans, Lactobacillus hilgardii, Lactobacillus reuteri, Lactobacillus fermentum, etc., can be used.

[0033] Examples of species belonging to the genus Leuconostoc include Leuconostoc mesenteroides and Leuconostoc oenos.

[0034] Examples of species belonging to the genus Pediococcus include Pediococcus acidilactici and Pediococcus pentosaceus.

[0035] Examples of species belonging to the genus Staphylococcus include Staphylococcus carnosus and Staphylococcus xylosus.

[0036] Examples of species belonging to the genus Tetragenococcus include Tetragenococcus halophilus.

[0037] Examples of species belonging to the genus Bacillus include Bacillus coagulans and Bacillus mesentericus.

[0038] In this invention, it is preferable to use Enterococcus species because they are excellent in maintaining and improving immune function, and it is particularly preferable to use Enterococcus faecalis.

[0039] As for Bifidobacteria, any species belonging to the genus Bifidobacterium can be used without restriction. Examples of Bifidobacterium species include Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium mongoliense. In this invention, one of these species may be used alone, or two or more species may be used in combination. Due to its superior effectiveness in maintaining and improving immune function, the use of Bifidobacterium longum is particularly preferable.

[0040] Butyrate-producing bacteria are a general term for bacteria that produce butyrate, and include bacteria from genera such as Clostridium, Anaerostipes, Butyrivibrio, Butyricicoccus, Coprococcus, Eubacterium, Faecalibacterium, Fusobacterium, and Roseburia. In this invention, the genus Clostridium is preferred because it is a Gram-positive rod-shaped bacterium that has spore-forming ability, exhibits high prebiotic effects, and is excellent in maintaining and improving immune function. Examples of Clostridium species include Clostridium butyricum, Clostridium acetobutyricum, Clostridium multifermentus, Clostridium bifermentans, Clostridium pasteurianum, Clostridium toanum, Clostridium perfringens, Clostridium tetanomorphum, Clostridium flavum, and Clostridium tertium. In this invention, Clostridium butyricum is particularly preferred.

[0041] (b) Sugars In the present invention, it is preferable that the sugars are at least one selected from monosaccharides, oligosaccharides, and sugar alcohols, as they are excellent in maintaining and improving immune function.

[0042] Examples of monosaccharides that can be used include glucose, fructose, mannose, and xylose. These monosaccharides may be used individually or in combination of two or more. In this invention, glucose is preferred as the monosaccharide because it is excellent in maintaining and improving immune function.

[0043] Examples of oligosaccharides include fructooligosaccharides, galactooligosaccharides, isomaltoligosaccharides, xylooligosaccharides, gentiooligosaccharides, lactosucrose, fucosyllactose, and nigerooligosaccharides. These oligosaccharides may be used individually or in combination of two or more. In this invention, fructooligosaccharides are preferred as they have excellent effects in maintaining and improving immune function.

[0044] Examples of sugar alcohols include reduced maltose, reduced starch syrup, xylitol, erythritol, sorbitol, mannitol, lactitol, and xylobiitol. In this invention, reduced maltose is preferred as the sugar alcohol because it is excellent in maintaining and improving immune function.

[0045] (c) Additives In the present invention, it is also preferable to include at least one additive selected from folic acid, selenium, and resveratrol, as it is excellent in maintaining and improving immune function.

[0046] Examples of selenium include selenium compounds containing the element selenium, and yeast containing selenium compounds. For example, sodium selenite, selenomethionine, and selenium yeast can be used as selenium. In this specification, when referring to the selenium content, it refers to the content in the form of these selenium compounds or in yeast containing selenium compounds.

[0047] Resveratrol refers to the resveratrol monomer. The resveratrol monomer is sometimes called "5-parahydroxystyrylresorcinol" or "3,4',5-stilbentriol". Resveratrol includes both its stereoisomers, trans-resveratrol and cis-resveratrol. Resveratrol can be used commercially from companies such as Tokyo Chemical Industries, Ltd., Sigma Corporation, and Wako Pure Chemical Industries, Ltd.

[0048] The composition of the present invention is excellent in maintaining and improving immune function, and therefore preferably contains 1 to 50 parts by mass of the third component per 1 part by mass of vitamin B6, more preferably 5 to 30 parts by mass, and even more preferably 10 to 20 parts by mass.

[0049] For example, when the composition of the present invention contains (a) beneficial bacteria, it is preferable that the composition contains 1 to 50 parts by mass of beneficial bacteria per 1 part by mass of vitamin B6, more preferably 5 to 30 parts by mass, and even more preferably 10 to 20 parts by mass, as these have excellent effects in maintaining and improving immune function.

[0050] For example, if the composition of the present invention contains (b) sugars, the sugar content in the composition is preferably 5 to 50 parts by mass, more preferably 5 to 30 parts by mass, and even more preferably 10 to 20 parts by mass, per 1 part by mass of vitamin B6, in order to be excellent in maintaining and improving immune function.

[0051] When the composition of the present invention contains additive (c) as a third component, the amount of additive in the composition is preferably 1 to 50 parts by mass, more preferably 5 to 30 parts by mass, and even more preferably 10 to 20 parts by mass of additive (c) per 1 part by mass of vitamin B6, from the viewpoint of being excellent in maintaining and improving immune function.

[0052] From the viewpoint of further enhancing the effects of the present invention, the content of the third component in the composition of the present invention is preferably 0.1% by mass or more and 60% by mass or less, more preferably 0.5% to 55% by mass, and particularly preferably 1% by mass or more and 50% by mass or less, based on the solid content of the composition. (a) The content of beneficial bacteria in the composition of the present invention is preferably 0.1% by mass or more and 60% by mass or less, and more preferably 1% by mass or more and 50% by mass or less, relative to the solid content of the composition, from the viewpoint of further enhancing the effects of the present invention. (b) The sugar content in the composition of the present invention is preferably 0.1% by mass or more and 60% by mass or less, and more preferably 1% by mass or more and 50% by mass or less, relative to the solid content of the composition, from the viewpoint of further enhancing the effects of the present invention. From the viewpoint of further enhancing the effects of the present invention, the content of additive (c) in the composition of the present invention is preferably 0.1% by mass or more and 60% by mass or less, and more preferably 1% by mass or more and 50% by mass or less, relative to the solid content of the composition.

[0053] The composition of the present invention may contain other components besides vitamin B6, vitamin B1, iron, zinc, and the third component, to the extent that they do not inhibit the expression of the predetermined effect of the present invention (maintenance and / or improvement of immune function). Examples of such other components include vitamins and minerals other than those listed above, proteins, dietary fiber such as insoluble dietary fiber, plants or plant products, yeast, etc. Furthermore, it may contain, as necessary, sweeteners, acidulants, colorants, thickeners, glazing agents, excipients, nutritional supplements, binders, lubricants, stabilizers, diluents, bulking agents, emulsifiers, food additives, seasonings, etc., which are commonly used in the food industry. The food and beverages of the present invention include health foods and beverages, foods for specified health uses, foods with functional claims, foods with nutritional function claims, health supplement foods, etc.

[0054] Furthermore, the composition of the present invention can be used by incorporating it into food and beverages, and by incorporating it into food and beverages, those food and beverages can be used as food and beverages. The types of food and beverages to which the composition can be used are not particularly limited, as long as the active ingredients for maintaining and / or improving immune function are not inhibited. Examples include milk and dairy products; beverages such as soft drinks, fruit juices, milk drinks, alcoholic beverages, sports drinks, and nutritional drinks; seasonings; alcoholic beverages; processed agricultural and forestry products; confectionery and bread; flour and noodles; processed marine products; processed livestock products; oils and fats; frozen prepared foods; retort foods; instant foods; and food ingredients.

[0055] In the present invention, it is preferable to use the CRL1505 as an oral composition such as a supplement or food or beverage, from the viewpoint of making it easy to take continuously for the purpose of improving immunity. Examples of supplement forms include tablets, capsules, powders, granules, and liquids, but tablets, capsules, and granules are preferred, and tablets and granules are particularly preferred, as they allow for more efficient intake of CRL1505.

[0056] The composition of the present invention preferably contains 0.5 to 2.0 mg of vitamin B6 orally per adult per day, more preferably 1.0 to 1.5 mg orally. Furthermore, it is preferable to orally administer a total of 1 to 30 mg of vitamin B1, iron, and zinc, more preferably 10 to 20 mg orally.

[0057] The composition of the present invention may be absorbed transdermally, but oral ingestion is preferable in that it is more effective.

[0058] The composition of the present invention can be produced by mixing vitamin B6, vitamin B1, iron, zinc, and a third component, and crushing and sieving as necessary. The produced composition is in powder form. Powder form includes granular form. There are no particular restrictions on the mixing method, crushing method, and sieving method, and known methods may be used.

[0059] The composition of the present invention is used to maintain and / or improve immune function. Specifically, ingesting the composition of the present invention promotes the secretion of IFN-γ from immune cells such as NK cells. The secreted IFN-γ acts on cellular immunity by activating NK cells and macrophages, as well as by inhibiting cell proliferation, thereby attacking and destroying infected cells such as viruses. As a result, immune function is maintained or improved (Th1 immune response). As mentioned above, a woman's immunity is said to decrease before and after menstruation, and this is deeply related to PMS and PMDD. Before and after menstruation, the activity of progesterone, which suppresses the function of the immune system, increases, and the uterus prepares for pregnancy. During this time, a lot of energy and nutrients are consumed, making it easy for the body to become deficient in nutrients, and it is said that because progesterone suppresses the aforementioned Th1 immune response, the immune system is more susceptible to being weakened than usual. For example, reference 1 states that progesterone, along with estrogen, fluctuates with the menstrual cycle, and reference 2 states that glucocorticoids (GC), a metabolite of progesterone, are secreted from the adrenal cortex and have a strong suppressive effect on the immune system, and that GC suppresses the production of inflammatory cytokines, and is thought to induce suppression of cytotoxic T cell activation and a decrease in macrophage phagocytic ability. In contrast, references 3 and 4 state that when IFN-γ is added to human granulosa luteal cells, progesterone production is suppressed. Based on the above, it is thought that increased IFN-γ expression suppresses progesterone production, thereby suppressing the immune deficiency during ovulation. Reference 1: “Physiological changes associated with the menstrual cycle”: a review, Obstet. Gynecol. Surv. 2009 Jan;64(1):p58-72. Reference 2: Bulletin of the Institute for Advanced Life Sciences, Tokai University, Vol. 3, March 2019, https: / / www.u-tokai.ac.jp / uploads / 2021 / 03 / 03_3.pdf (Retrieved March 22, 2025) Reference 3: “Interactions between interferon gamma, tumor necrosis factor alpha, and interleukin-1 in modulating progesterone and oestradiol production by human luteinized granulosa cells in culture”, Hum. Reprod. 1992 Nov;7(10): p 1361-4. Reference 4: “Cytokine modulation of progesterone and estradiol secretion in cultures of luteinized human granulosa cells”, J Clin. Endocrinol. Metab. 1992 Jul;75(1):p254-8.

[0060] Furthermore, the secretion of estrogen in women, which is thought to contribute to immune system enhancement, peaks in their 20s and gradually declines, with a significant decrease during menopause. This is considered one of the factors contributing to a decline in women's immunity. A decrease in estrogen is also thought to be linked to PMS and PMDD. For these reasons, it is believed that there is a relationship between immune system enhancement and the improvement of PMS, PMDD, etc. For example, several components that increase the expression of IFN-γ are known to improve PMS symptoms (see references 5 and 6 (which describe improvement of PMS symptoms) and references 7, 8, and 9 (which describe the enhancement of IFN-γ) for chromium, γ-tocopherol, and γ-tocotrienol). It has also been pointed out that stress reduction through immune system enhancement improves PMDD. Reference 5) “Chromium Supplementation for Menstrual Cycle-Related Mood Symptoms”: Journal of Dietary Supplements: Vol 10, No 4 2013 Dec;10(4):p345-56. Reference 6) “Effects of γ-tocopherol, γ-tocotrienol, equol, and calcium-containing foods on reducing nonspecific symptoms during the luteal phase: A randomized, placebo-controlled, double-blind, crossover comparative study” Journal of Japanese Society for Women's Health 29(4) p 578-587, 2022. Reference 7) “Effects of Supplemental Chromium Nanoparticles on IFN-γ expression of Heat Stress Broilers” Biological Trace Element Research, 2022 Jan;200(1):p339-347. Reference 8) “Supplementation with γ-tocopherol attenuates endotoxin-induced airway neutrophil and mucous cell responses in rats” Free Radic. Biol. Med. 2014 Mar:68: p101-9. Reference 9) “Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation” Clin. Exp. Immunol. 2021 Nov;206(2):p161-172.

[0061] Based on the above, it is expected that the composition of the present invention, when taken orally before, during, or after menstruation or during menopausal symptoms, will promote the expression of IFN-γ in immune cells, thereby maintaining and / or improving immune function in response to excessive declines in immune function that occur during these periods. In particular, it is expected that the composition of the present invention can be suitably used to improve health problems associated with symptoms specific to women, selected from menstruation, pregnancy, childbirth, infertility, and menopausal symptoms. For example, the composition of the present invention can be used as a composition for maintaining or improving physical and / or mental state before and / or during menstruation.

[0062] "For maintaining or improving physical and / or mental state before and / or during menstruation" refers to use to improve or avoid various unpleasant symptoms that are said to be partly caused by fluctuations in female hormones, etc. In particular, premenstrual syndrome ("PMS") appears during the period called the "luteal phase," which is before the start of menstruation (for example, 3 to 10 days before) and during menstruation. Specific mental symptoms include irritability, tension, anxiety, drowsiness, distractibility, depression, aggression, changes in appetite, and cravings for sweets or salt. Physical symptoms include general swelling, breast pain, weight gain, abdominal bloating, dizziness, and hot flashes. Symptoms often last for several days after the start of menstruation and tend to recur with each menstrual cycle. Premenstrual dysphoric disorder (PMDD) refers to a case of premenstrual syndrome ("PMS") in which emotional instability is particularly pronounced. Symptoms of PMDD include depressed mood, anxiety / tension, emotional instability, anger / irritability, and other characteristic symptoms such as changes in eating behavior and sleep disturbances that appear before menstruation, interfering with social activities and interpersonal relationships.

[0063] Menopausal symptoms also include unpleasant symptoms. Specifically, these include hot flashes, mental symptoms, and insomnia. For example, mental symptoms include irritability, anxiety, depression (feelings of sadness, etc.), and low mood. Other unpleasant symptoms include drowsiness, headaches, dizziness, tinnitus, forgetfulness, impaired judgment / concentration, insomnia, and fatigue.

[0064] The present invention also provides a method for maintaining or improving physical and / or mental state before and / or during menstruation, characterized by administering a composition comprising vitamin B6 and at least one selected from iron, zinc, and vitamin B1. In yet another aspect, the present invention provides the use of a composition comprising vitamin B6 and at least one selected from iron, zinc, and vitamin B1 for maintaining or improving physical and / or mental state before and / or during menstruation. In yet another aspect, the present invention provides the use of a composition comprising vitamin B6 and at least one selected from iron, zinc, and vitamin B1 for producing an agent for maintaining or improving physical and / or mental state before and / or during menstruation. In the present invention, "improvement" includes alleviation, prevention, and treatment of the above-mentioned unpleasant symptoms. "Maintaining" includes avoiding the above-mentioned unpleasant symptoms.

[0065] The composition of the present invention is preferably taken during PMS. It is also preferable to take the composition of the present invention during menopause. During pregnancy, the Th2 response tends to be dominant, and immunity tends to decrease. If immunity decreases excessively, the possibility of the mother contracting an infection caused by bacteria or viruses, for example, or the possibility of the infection being transmitted from the mother to the fetus increases. Therefore, too much decrease in immunity is also a problem, and it is necessary to improve or maintain immunity. Immunity tends to decrease especially after childbirth. In response to this, the present invention contributes to improving immunity during pregnancy and after childbirth, especially after childbirth, so it is also preferable to orally take the composition of the present invention during pregnancy and after childbirth, especially after childbirth. [Examples]

[0066] The present invention will be described below based on examples. However, the present invention is not limited to the following examples. Unless otherwise specified, "parts" below refers to "parts by mass," and "%" refers to "mass percent." Regarding iron and zinc, the content amounts listed in each table are based on the compound.

[0067] The following materials were used as raw materials for the compositions of the examples and comparative examples. (Vitamins, iron, zinc) • Vitamin B6 (chemical name: pyridoxine hydrochloride) • Vitamin B1 (chemical name: thiamine hydrochloride) • Vitamin D (chemical name: calciferol) • Iron (chemical name: iron(II) chloride tetrahydrate) • Zinc (chemical name: anhydrous zinc gluconate) (Beneficial bacteria) ·Enterococcus faecalis (bacterial name: Enterococcus faecalis LAB2PRO, number of bacteria 500 billion / g) • Bifidobacteria (bacterial name: Bifidobacterium longum, bacterial count: 150 billion / g) ·Butyric acid bacteria (bacteria name: Clostridium butyricum, number of bacteria 1 billion / g) (Sugars) Glucose • Fructooligosaccharides • Reduced maltose (Additives) Folic acid • Selenium (Selenium-containing yeast, containing 0.2% or more selenium. The amount of selenium listed in Table 4 is the amount for selenium-containing yeast.) • Resveratrol (manufactured by Tokyo Chemical Industry Co., Ltd.)

[0068] [Test 1] This study investigates the effects of combinations of vitamin B6 with vitamin B1, iron, or zinc, and the relative content of vitamin B1, iron, or zinc in relation to vitamin B6, on immune function. The test substances for Examples 1-10 and Comparative Examples 1-5 were prepared using the raw materials listed in Table 1. When multiple raw materials were used, the test substances were prepared by mixing the multiple raw materials. The amounts of raw materials used are shown in Table 1.

[0069] The immune activation was evaluated using the following method. [Test Method] (1) Human NK-like cell line (KHYG-1) 2 × 10 4 Seeds were seeded to a cell / well ratio and incubated in culture medium for 24 hours in a 37°C, 5% CO2 incubator. (2) After removing 50 μL of the culture medium, 50 μL / well of culture medium containing the test substance at twice the final concentration (20 μg / mL) was added, and the culture was incubated at 37°C in a 5% CO2 incubator for 24 hours. (3) The cells were collected in Eppendorf tubes, and RNA was recovered using the CellAmp™ Direct RNA Prep Kit for RT-PCR (Real Time) (TaKaRa). (4) The recovered RNA was subjected to real-time PCR using One Step TB Green® PrimerScript™ RT-PCR Kit II (Perfect Real Time) (TaKaRa). The gene expression level of IFN-γ was measured using an IFN-γ primer (QIAGEN). In addition, as an endogenous control, the gene expression level of ACTB (also known as β-actin) was measured using an ACTB primer (QIAGEN), and the relative gene expression level of the test substance was calculated by determining the ratio of the IFN-γ gene expression level to the ACTB gene expression level. The results are shown in Table 1.

[0070] [Table 1]

[0071] [Test Results] Since the total amount of the test substance is the same in each example and comparative example, if it is an additive effect, it is presumed to be the sum of the content ratios of the gene expression levels of the individual raw materials. However, as shown in Table 1, Examples 1-10, which used vitamin B6 in combination with iron, zinc, or vitamin B1, showed higher relative gene expression levels compared to Comparative Examples 1-4, which used vitamin B6, iron, zinc, or vitamin B1 alone. This result suggests that the secretion of IFN-γ is promoted by using vitamin B6 in combination with iron, zinc, or vitamin B1. Furthermore, Examples 9 and 10, which used a combination of vitamin B6 and vitamin B1, showed higher relative gene expression levels compared to Comparative Example 5, which used a combination of vitamin B6 and vitamin D. This result suggests that, in order to promote IFN-γ gene expression, it is necessary to combine vitamin B6 and vitamin B1 among the vitamins.

[0072] Furthermore, despite using the same raw materials, Examples 1 and 2 showed higher relative gene expression levels compared to Examples 3 and 4. The difference between Examples 1 and 2 and Examples 3 and 4 lies in the iron content relative to vitamin B6. This result suggests that setting the iron content relative to vitamin B6 within a specific range further promotes IFN-γ secretion.

[0073] Furthermore, Examples 5-8 used a combination of vitamin B6 and zinc. All of Examples 5-8 showed high relative gene expression levels. This result suggests that IFN-γ secretion is promoted when the zinc content relative to vitamin B6 is within a specific range.

[0074] Furthermore, both Examples 9 and 10 exhibited high relative gene expression levels. This result suggests that IFN-γ secretion is promoted when the vitamin B1 content relative to vitamin B6 is within a specific range.

[0075] [Exam 2] This study investigates the effects of combinations of vitamin B6 and vitamin B1 with iron and / or zinc on immune function. The test substances for Examples 11-15 were prepared using the raw materials listed in Table 2. When multiple raw materials were used, the test substances were prepared by mixing the multiple raw materials. The amounts of raw materials used are shown in Table 2. The prepared test substance was evaluated for immune activation using the same method as in Test 1. The results are shown in Table 2. For reference, the evaluation results for Examples 1, 5, and 9 are also shown in Table 2.

[0076] [Table 2]

[0077] [Test Results] As shown in Table 2, Example 11, consisting of vitamin B6, vitamin B1, and iron, showed even higher relative gene expression levels than Example 1, consisting of vitamin B6 and iron, and Example 9, consisting of vitamin B6 and vitamin B1. Furthermore, Examples 12 and 13, consisting of vitamin B6, vitamin B1, and zinc, showed even higher relative gene expression levels than Example 5, consisting of vitamin B6 and zinc, and Example 9, consisting of vitamin B6 and vitamin B1. These results suggest that combining vitamin B6 and vitamin B1 with iron or zinc further promotes IFN-γ gene expression.

[0078] Furthermore, Examples 14 and 15, consisting of vitamin B6, vitamin B1, iron, and zinc, showed even higher relative gene expression levels than Examples 11-13. These results suggest that combining all of vitamin B6, vitamin B1, iron, and zinc further promotes IFN-γ gene expression.

[0079] Furthermore, both Examples 14 and 15 showed high relative gene expression levels. This result suggests that IFN-γ secretion is promoted when the total amount of iron and zinc relative to the total amount of vitamin B6 and vitamin B1 is within a specific range, for example, between 6 and 9 parts by mass.

[0080] [Exam 3] This study aims to investigate the effects of the third component on immune function. The test substances for Examples 16-24 and Comparative Examples 6-16 were prepared using the raw materials listed in Tables 3 and 4. When multiple raw materials were used, the test substances were prepared by mixing the multiple raw materials. The amounts of raw materials used are shown in Tables 3 and 4. The prepared test substance was evaluated for immune activation using the same method as in Test 1. The results are shown in Tables 3 and 4. For reference, the evaluation results for Examples 14 and 15 are also shown in Table 4.

[0081] [Table 3]

[0082] [Table 4]

[0083] [Test Results] As shown in Tables 3 and 4, Examples 16-24, consisting of vitamin B6, vitamin B1, iron, zinc, and a third component (Enterococcus faecalis, Bifidobacterium, Butyrate-producing bacteria, glucose, fructooligosaccharides, reduced maltose, folic acid, selenium, or resveratrol), showed higher relative gene expression levels compared to Comparative Examples 6-14, which consisted of a third component, Comparative Example 15, which consisted of vitamin B6 and selenium, and Comparative Example 16, which consisted of vitamin B1 and selenium. Furthermore, Examples 16-24 showed even higher relative gene expression levels than Examples 14 and 15, which consisted of vitamin B6, vitamin B1, iron, and zinc. These results suggest that the use of a third component promotes IFN-γ secretion.

[0084] As is clear from the above results, the present invention suggests that IFN-γ secretion is promoted. This means that by using the composition of the present invention, NK cells are more activated and immune function is improved. The health problems associated with the aforementioned women-specific symptoms are related to a weakened immune system. Therefore, by using the composition of the present invention, it is possible to maintain and / or improve the immune function of women, and in particular improve health problems associated with women-specific symptoms selected from menstruation, childbirth, infertility, and menopausal disorders.

Claims

1. Vitamin B6 and, A composition for maintaining and / or improving immune function, comprising at least one selected from iron, zinc, and vitamin B1.

2. Vitamin B6, Vitamin B1 and, A composition for maintaining and / or improving immune function, containing at least one selected from iron and zinc.

3. Vitamin B6, Vitamin B1, Iron and A composition containing zinc for maintaining and / or improving immune function.

4. Furthermore, the composition for maintaining and / or improving immune function according to any one of claims 1 to 3, comprising at least one component selected from the group consisting of (a) to (c) below. (a) At least one beneficial bacterium selected from lactic acid bacteria, bifidobacteria, and butyrate-producing bacteria. (b) At least one sugar selected from glucose, fructooligosaccharides, and reduced maltose. (c) At least one additive selected from folic acid, selenium, and resveratrol.

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