Oral composition

Abstract

Provided is an oral composition that can be used to promote production of isoflavones in an individual and / or to increase the blood concentration, urinary concentration, and / or fecal concentration of isoflavones in an individual. In the oral composition, one or more first isoflavones and one or more amino acids represented by formula (I) [in formula (I), R is an amino group, a guanidino group, or a carbamoyl group] or salts thereof are administered in combination.

Description

Oral composition

[0001] The present disclosure relates to an oral composition.

[0002] Isoflavones mainly contained in soybeans and the like are known to have beneficial effects such as prevention of osteoporosis, alleviation of menopausal symptoms, alleviation of premenstrual syndrome symptoms, and prevention of breast cancer and prostate cancer. It is known that by ingesting daidzein, which is one type of isoflavone, equol, which is a daidzein metabolite produced in the intestine, is produced.

[0003] However, there are individual differences in the ability to produce equol, and a method capable of promoting equol production in those who do not have sufficient equol production ability is useful.

[0004] Japanese Patent Application Laid-Open No. 2005-232074

[0005] An object of the present disclosure is to provide an oral composition that can be used to promote the production of isoflavones in an individual and / or increase the blood concentration, urine concentration, and / or fecal concentration of isoflavones in an individual.

[0006] The present disclosure includes the following aspects. [1] An oral composition in which one or more first isoflavones and one or more amino acids represented by the following formula (I): [In formula (I), R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof are administered in combination. [2] An oral composition for promoting the production of second isoflavones in an individual and / or increasing the blood concentration, urine concentration, and / or fecal concentration of second isoflavones in an individual, which contains one or more amino acids represented by the following formula (I): [In formula (I), R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof.

[0007] According to the present disclosure, an oral composition that can be used to promote the production of isoflavones in an individual and / or increase the blood concentration, urine concentration, and / or fecal concentration of second isoflavones in an individual can be provided.

[0008] This graph shows the amount of equol produced on day 14 from the start of the experiment when daidzein and citrulline or arginine were added in vitro. This graph shows the amount of equol in fecal samples on day 14 from the start of administration when daidzein and citrulline (low-dose group, high-dose group) or arginine (low-dose group) were administered to rats. This graph shows the amount of equol in urine samples on day 14 from the start of administration when daidzein and citrulline (low-dose group, high-dose group) or arginine (low-dose group) were administered to rats. This graph shows the amount of equol in plasma samples on day 14 from the start of administration when daidzein and citrulline (low-dose group, high-dose group) or arginine (low-dose group) were administered to rats. This graph shows the amount of equol in urine samples at 8 days from the start of administration (daidzein-only administration) and at the end of the entire administration period (22 days from the start of administration) in mice, after administration of daidzein alone (high-dose, medium-dose, and low-dose groups) for 7 days (white bars), and then administration of daidzein (high-dose, medium-dose, and low-dose groups) and citrulline for 14 days (black bars).

[0009] The following describes in detail one embodiment of the present disclosure, but the scope of the present disclosure is not limited to the embodiment described herein, and various modifications can be made without departing from the spirit of the present disclosure. Each configuration and combination thereof in each embodiment is an example, and additions, omissions, substitutions, and other modifications can be made as appropriate without departing from the spirit of the present invention. The present disclosure is not limited by the embodiments. Each aspect disclosed herein can be combined with any other features disclosed herein. If multiple upper and lower limits are given for a particular parameter, any combination of these upper and lower limits can be used to create a suitable numerical range. The lower and / or upper limits of the numerical range described herein may be replaced with numerical values ​​within that range, as shown in the examples. The expression "X to Y" indicating a numerical range means "X or more and Y or less". If a particular description given for one embodiment also applies to other embodiments, that description may be omitted in the other embodiments. Any numerical range or value essentially includes the range of errors that inevitably arise from the standard deviation found in each of those test measurements. Unless otherwise noted, each individual value of a numerical range is incorporated herein in the same way that it is individually listed herein. In this specification, “includes” means including at least a part of a component, and includes cases where it consists only of that component.

[0010] [First Embodiment: Oral Composition] The oral composition according to this embodiment will be described below. When simply referred to as "oral composition" or "composition," the description refers to both oral composition (1) and oral composition (2).

[0011] The oral composition (1) according to this embodiment comprises one or more first isoflavones and the following formula (I): This is an oral composition administered in combination with one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group], or a salt thereof.

[0012] When one or more first isoflavones are administered in combination with one or more amino acids represented by formula (I) or their salts, the effects of promoting the production of second isoflavones in the individual, and / or increasing the blood, urinary, and / or fecal concentrations of second isoflavones in the individual, are more easily obtained.

[0013] In one embodiment, the oral composition (1) may be an oral composition comprising one or more amino acids represented by formula (I) or a salt thereof, and administered in combination with one or more first isoflavones. The oral composition (1) may be an oral composition comprising one or more amino acids represented by formula (I) or a salt thereof, and administered in combination with one or more first isoflavones.

[0014] In one embodiment, the oral composition (1) may be an oral composition comprising one or more first isoflavones and administered in combination with one or more amino acids represented by formula (I) or salts thereof. The oral composition (1) may be an oral composition comprising one or more first isoflavones and administered in combination with one or more amino acids represented by formula (I) or salts thereof.

[0015] In one embodiment, the oral composition (1) is an oral composition comprising one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof.

[0016] In one embodiment, the oral composition (1) may be an oral composition for promoting the production of a second isoflavone in an individual, and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavone in the individual.

[0017] In one embodiment, the oral composition (1) may be an oral composition administered in combination with one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof, for promoting the production of second isoflavones in an individual, and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavones in an individual.

[0018] In this embodiment, the oral composition (2) is the following formula (I): An oral composition comprising one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof, for promoting the production of a second isoflavone in an individual, and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual.

[0019] The oral composition (2) can enhance the ability of an individual to produce a second isoflavone from a first isoflavone, and when administered to an individual, it facilitates the promotion of the production of the second isoflavone in the individual, and / or increases the blood, urine, and / or fecal concentrations of the second isoflavone in the individual.

[0020] In one embodiment, oral composition (2) may be an oral composition administered in combination with an oral composition containing a first isoflavone. In one embodiment, oral composition (2) may be an oral composition for administration in combination with an oral composition containing a first isoflavone. In one embodiment, oral composition (2) may be an oral composition administered in combination with an oral composition containing a first isoflavone to promote the production of a second isoflavone in an individual, and / or to increase the blood, urine, and / or fecal concentrations of the second isoflavone in an individual. Oral composition (2) may be administered in combination with an oral composition containing a first isoflavone to more easily achieve a greater effect in promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual.

[0021] In one embodiment, the first isoflavones and the amino acid represented by formula (I) or a salt thereof can be used to prepare an oral composition. In one embodiment, the amino acid represented by formula (I) or a salt thereof can be used to prepare an oral composition administered in combination with the first isoflavones. In one embodiment, the first isoflavones can be used to prepare an oral composition administered in combination with the amino acid represented by formula (I) or a salt thereof. In one embodiment, the amino acid represented by formula (I) or a salt thereof can be used to prepare an oral composition for promoting the production of a second isoflavone in an individual, and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual.

[0022] The oral composition may contain, in addition to one or more first isoflavones and / or one or more amino acids represented by formula (I) or salts thereof, one or more non-functional components that are permissible for the use (food or pharmaceutical) described in the second embodiment. Examples of non-functional components include additives such as acidulants, sweeteners, excipients, surfactants, lubricants, flavoring agents, fragrances, colorants, stabilizers, and preservatives. Examples of excipients include mannitol, erythritol, xylitol, trehalose, lactose, maltose, maltitol, glucose, sucrose, fructose, mannose, sorbitol, amylose, light anhydrous silicic acid, hydrated silicon dioxide, anhydrous calcium phosphate, anhydrous calcium hydrogen phosphate, aluminum metasilicate, calcium silicate, magnesium silicate, and magnesium oxide. Examples of surfactants include nonionic surfactants, such as sorbitan fatty acid esters like sorbitan monocaprylate, sorbitan monolaurate, and sorbitan monopalmitate, and glycerin fatty acid esters like glycerin monocaprylate, glycerin monomyritate, and glycerin monostearate, which have an HLB of 6 to 18. Other non-functional ingredients include, for example, water, saline solution, alcohol, silicone, wax, petrolatum, vegetable oil, polyethylene glycol, propylene glycol, liposomes, gelatin, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, fragrance oil, fatty acid monoglycerides and diglycerides, petroethral fatty acid esters, hydroxymethylcellulose, and polyvinylpyrrolidone.

[0023] Whether or not the administration of an oral composition promotes the production of a second isoflavone in an individual, and / or whether the blood, urine, and / or fecal concentrations of the second isoflavone increase in the individual, can be confirmed by measuring the concentration of the second isoflavone in samples such as blood (whole blood, plasma, serum, etc.), urine, and feces. For example, by taking samples from an individual before and after administration of the oral composition, and comparing the concentration of the second isoflavone after administration with that before administration, if the concentration of the second isoflavone increases, it can be confirmed that the production of the second isoflavone is promoted in the individual, and / or the blood, urine, and / or fecal concentrations of the second isoflavone increase in the individual. Based on the measured concentration of the second isoflavone, whether or not the production of the second isoflavone is promoted in the individual, and / or whether the blood, urine, and / or fecal concentrations of the second isoflavone increase in the individual, can be determined by a person skilled in the art based on well-known technology. For example, the determination may be made based on whether or not there is a statistically significant difference using any statistical processing method, or based solely on the measured values ​​regardless of whether or not there is a statistically significant difference, or a reference value or reference range may be set before measurement and the determination may be made by comparing with said reference value or reference range.

[0024] It is presumed that when the production of the second isoflavone is promoted in an individual, it is absorbed into the body from the intestines, enters the bloodstream, and is then excreted in the urine. It is also presumed that the second isoflavone that remains in the intestines without being absorbed into the body is excreted in the feces. Therefore, by measuring the concentration of the second isoflavone in samples such as blood (whole blood, plasma, serum, etc.), urine, and feces, it is possible to confirm whether the blood concentration, urine concentration, and / or fecal concentration of the second isoflavone increases in individuals administered the oral composition, as well as whether the production of the second isoflavone is promoted.

[0025] Here, the equol in the sample can be measured by methods well known to those skilled in the art, for example, by high-performance liquid chromatography (HPLC).

[0026] (Individual) The "individual" to which the oral composition is administered may be any individual in which it is desired that the production of the second isoflavone be promoted and / or the blood, urine, and / or fecal concentrations of the second isoflavone be increased. The oral composition is not limited to the extent that it is possible to obtain the effect of promoting the production of the second isoflavone and / or increasing the blood, urine, and / or fecal concentrations of the second isoflavone in the individual, but the animal species is preferably a mammal. Examples of mammals include humans and non-human mammals. Examples of non-human mammals include rats, mice, dogs, cats, monkeys, pigs, and cattle.

[0027] In one embodiment, the promotion of the production of the second isoflavone "in an individual (or within an individual)" is preferably the promotion of the production of the second isoflavone in the intestines of a mammalian individual. This is because it has been reported that intestinal bacteria present in the intestines of mammals such as humans produce second isoflavones, including equol. Here, the intestines may be the small intestine (including the jejunum and ileum), the large intestine (including the colon and rectum), or both, but for example, if the second isoflavone is equol, the small intestine is preferred.

[0028] For example, in humans, some individuals can produce a second type of isoflavone (e.g., equol) by ingesting foods such as soy products containing isoflavones (e.g., individuals with bacteria that produce the second type of isoflavone), while others cannot (e.g., individuals without bacteria that produce the second type of isoflavone). Even among individuals that can produce the second type of isoflavone, there are individual differences ranging from individuals with high production capacity to individuals with low production capacity. It is preferable that the target of the oral composition is an individual that can produce the second type of isoflavone. By administering the oral composition to an individual that can produce the second type of isoflavone, it becomes easier to obtain the effect of promoting the production of the second type of isoflavone, and / or increasing the blood concentration, urine concentration, and / or fecal concentration of the second type of isoflavone in the individual. In one embodiment, the target of administration is an individual that can produce the second type of isoflavone, but it is preferable that it is an individual with low production capacity. Administering the oral composition to individuals with low production capacity for the second isoflavone makes it easier to promote the production of the second isoflavone and / or increase the blood, urinary, and / or fecal concentrations of the second isoflavone in the individual.

[0029] The ability of an individual to produce a second isoflavone can be determined by known methods. For example, it may be determined by testing whether a second isoflavone (e.g., equol) is present in samples such as blood (whole blood, plasma, serum, etc.), urine, or feces collected from the individual in question. The second isoflavone in the sample can be measured by methods well known to those skilled in the art, such as high-performance liquid chromatography (HPLC).

[0030] (Isoflavones) In plants, such as soybeans which contain isoflavones, isoflavones exist as glycosides covalently bonded to sugars, namely daidzin, glycitin, and genistin, with only very small amounts present in the aglycone form. Some of these glycosides are further malonylated and acetylated. When these glycosides enter the bodies of humans and animals, they are converted into daidzein, glycitein, and genistein, respectively, by digestive enzymes or enzymes produced by intestinal bacteria, such as β-glucosidase. Furthermore, it is known that intestinal bacteria convert daidzein to dihydrodaidzein, then to O-desmethylangolensin (O-DMA), or to equol, and genistein to dihydrogenistein, then to 5-hydroxyequol.

[0031] Isoflavones include daidzeins, genisteines, and glyciteins. Daidzeins include daidzein, daidzin, malonyldaidzin, acetyldaidzin, dihydrodaidzein, and equol. Genisteins include genistin, malonylgenistin, acetylgenistin, genistein, dihydrogenistein, and 5-hydroxyequol. Glyciteins include glycitin, malonylglycitin, acetylglycitin, glycitein, and dihydroglycitein.

[0032] In this embodiment, "first isoflavones" refers to components contained in the oral composition, and "second isoflavones" refers to isoflavones that are metabolites produced in individuals to whom the first isoflavones have been orally administered, through the action of enzymes produced by intestinal bacteria, etc. Therefore, the second isoflavones are isoflavones produced downstream of the first isoflavones in the metabolic pathway in the individual.

[0033] In the oral composition, the first isoflavone may be used alone or in any combination of two or more types, and may be used in combination of two or more types that differ in origin, preparation method, etc.

[0034] In one embodiment, the first and second isoflavones are preferably daidzeins or genisteins. The first isoflavone is preferably daidzein, daidzin, malonyldaidzin, acetyldaidzin, or dihydrodaidzein, and the genistein is preferably genistin, malonylgenistin, acetylgenistin, genistein, or dihydrogenistein. The second isoflavone is preferably daidzein, dihydrodaidzein, or equol, and the genistein is preferably genistein, dihydrogenistein, or 5-hydroxyequol.

[0035] In one embodiment, the first isoflavone is daidzin, and the second isoflavone is daidzein, dihydrodaidzein, and / or equol. In one embodiment, the first isoflavone is daidzein, and the second isoflavone is dihydrodaidzein or equol. In one embodiment, the first isoflavone is dihydrodaidzein, and the second isoflavone is equol. In one embodiment, it is preferable that the first isoflavone is daidzein and the second isoflavone is equol.

[0036] In one embodiment, the first isoflavone may be genistein and the second isoflavone may be dihydrogenistein or 5-hydroxyequol, or the first isoflavone may be dihydrogenistein and the second isoflavone may be 5-hydroxyequol.

[0037] (Method of obtaining isoflavones) In one embodiment, the first isoflavones can be prepared by extraction from natural products and / or by chemical synthesis, but it is preferable that they be isoflavones derived from natural products prepared by extraction from natural products. Chemically synthesized isoflavones are prone to contamination with impurities resulting from the chemical synthesis process, while isoflavones derived from natural products are less likely to contain or avoid such impurities, thus offering higher safety when administered to individuals and making them more suitable as materials for oral compositions.

[0038] Here, chemical synthesis can be carried out by any method well known to those skilled in the art.

[0039] When isoflavones are derived from natural products, they are preferably plant-derived. The plant is not limited to those containing isoflavones, but considering the isoflavone content, it is preferably a leguminous plant, more preferably one or more of soybeans, kudzu, red clover, alfalfa, and licorice, and even more preferably soybeans. The plant may also be a part isolated from a plant. Considering the isoflavone content, if the plant is soybeans, it is preferably soybean seeds, and even more preferably soybean hypocotyls. Furthermore, the plant may be, for example, in its raw state, or a processed product obtained by heat treatment, drying, steaming, etc., of the whole or a part of the plant. For example, if the plant is soybean seeds, processed products include tofu, fried tofu, soy milk, natto, soy sauce, miso, tempeh, etc. The plant is not limited by its origin, variety, etc., as long as the contained daidjin is not significantly lost. Here, "soybean hypocotyl" refers to the part of the soybean that develops into the sprout and radicle during germination, and is known to contain a large amount of isoflavones. Furthermore, the soybean hypocotyl may have undergone defatting or deproteinization treatment. The shape of the soybean hypocotyl is not limited and may be in powder form, or in crushed or broken granules or lumps.

[0040] In one embodiment, isoflavones can be prepared by subjecting any of the above natural products (including processed products thereof) to an arbitrary extraction process. Examples of the process include methods well known to those skilled in the art such as filtration, various column chromatographies, crystallization methods, centrifugation methods, and the like.

[0041] Here, in the preparation of the first isoflavones, components mixed in the preparation process, for example, components derived from natural products but other than isoflavones, may not be completely separated and may remain. Therefore, the oral composition according to the present embodiment also includes an aspect in which components resulting from the preparation process of the first isoflavones are included.

[0042] (Amino acid represented by formula (I)) The amino acid represented by formula (I) is the following formula (I): [In formula (I), R is an amino group, a guanidino group, or a carbamoyl group] refers to an amino acid represented by the formula.

[0043] The amino acid contained in the oral composition according to the present embodiment may be a salt of the amino acid represented by formula (I). Non-limiting examples of salts of amino acids include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, and the like.

[0044] Non-limiting examples of acid addition salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, etc., and organic acid salts such as acetate, maleate, fumarate, citrate, malate, lactate, α-ketoglutarate, gluconate, caprylate, etc.

[0045] Non-limiting examples of metal salts include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and calcium salt, aluminum salt, zinc salt, etc.

[0046] Non-limiting examples of ammonium salts include salts such as ammonium and tetramethylammonium.

[0047] Non-limiting examples of organic amine addition salts include salts such as morpholine and piperidine.

[0048] Non-exclusive examples of amino acid addition salts include salts of glycine, phenylalanine, lysine, aspartic acid, and glutamic acid.

[0049] The amino acid represented by formula (I) or its salt is preferably citrulline, arginine, or ornithine, or one or more salts thereof (a salt of citrulline, a salt of arginine, and / or a salt of ornithine), and may be citrulline, arginine, or ornithine. In one embodiment, the salt of arginine is arginine hydrochloride.

[0050] The presence of citrulline, arginine, or ornithine, or their salts, in individuals administered the oral composition makes it easier to promote the production of a second isoflavone and / or increase the blood, urinary, and / or fecal concentrations of the second isoflavone.

[0051] The amino acid may be in L-form, D-form, or L-form (racemic), but considering its general presence in mammalian individuals, the L-form is preferred.

[0052] In oral compositions, the amino acid represented by formula (I) or its salt may be used alone or in any combination of two or more, and may be used in combination of two or more that differ in origin, preparation method, etc.

[0053] In one embodiment, the amino acid is preferably one or more amino acids including the L-form of citrulline (L-citrulline), and may also be L-citrulline.

[0054] (Method of obtaining amino acids represented by formula (I)) Amino acids represented by formula (I) or salts thereof can be prepared by methods well known to those skilled in the art. Known methods for preparing amino acids include fermentation, enzymatic methods, extraction methods, and synthesis methods. In the fermentation method, molasses derived from plants (e.g., sugarcane, corn, cassava, etc.) can be used as a raw material and cultured with amino acid-producing bacteria under appropriate conditions to prepare the target amino acid through fermentation by the bacteria. In the enzymatic method, the target amino acid can be prepared by enzymatic treatment of an amino acid precursor substance. In the extraction method, the target amino acid can be prepared by performing a well-known extraction treatment on a raw material protein containing the target amino acid. In the synthesis method, the target amino acid can be prepared using a well-known chemical reaction. Amino acids represented by formula (I) or salts thereof may also be obtained as commercially available products.

[0055] In the preparation of the amino acid represented by formula (I) or its salt, components other than the amino acid represented by formula (I) or its salt, which are derived from natural products, may be introduced during the preparation process and remain unseparated. Therefore, the oral composition according to this embodiment also includes embodiments that contain components resulting from the preparation process of the amino acid represented by formula (I) or its salt.

[0056] (Administration of oral composition) The effective dose, duration of administration, and / or interval of administration of the oral composition shall be appropriately determined by those skilled in the art based on the animal species, age, weight, disease, etc. of the target individual, the route of administration, the administration schedule, the formulation form, etc., and shall not be limited as long as the effect of promoting the production of the desired second isoflavone and / or increasing the blood concentration, urinary concentration, and / or fecal concentration of the second isoflavone is obtained in the individual.

[0057] In one embodiment, one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof in the oral composition (1) may be administered to an individual simultaneously, separately, or consecutively.

[0058] In one embodiment, one or more amino acids represented by formula (I) or salts thereof in the oral composition (2) may be administered to an individual simultaneously, separately, or consecutively with an oral composition (food composition, pharmaceutical composition), food, or pharmaceutical, etc., containing the first isoflavones.

[0059] In an oral composition, when one or more first isoflavones and one or more amino acids represented by formula (I) or their salts are administered separately or consecutively, the order in which the one or more first isoflavones and the one or more amino acids represented by formula (I) or their salts are administered may vary, but it is preferable that the one or more first isoflavones and the one or more amino acids represented by formula (I) or their salts are administered to the individual at a timing that allows them to exist simultaneously in the individual's body for any desired period of time. For example, one or more first isoflavones and one or more amino acids represented by formula (I) or their salts may be administered within 24 hours after the other is administered, one or more first isoflavones and one or more amino acids represented by formula (I) or their salts may be administered within 12 hours after the other is administered, one or more first isoflavones and one or more amino acids represented by formula (I) or their salts may be administered within 6 hours after the other is administered, one or more first isoflavones and one or more amino acids represented by formula (I) or their salts may be administered within 3 hours after the other is administered, one or more first isoflavones and one or more amino acids represented by formula (I) or their salts may be administered simultaneously.

[0060] Here, "administration" of an oral composition includes "ingestion" when the oral composition is a food composition or when the oral composition is contained in food.

[0061] In one embodiment, in oral composition (1), or when oral composition (2) is administered in combination with an oral composition containing a first isoflavone, the amount of one or more first isoflavones (component A) and one or more amino acids represented by formula (I) or their salts (component B) may be 1 to 50 parts by mass of component B per 1 part by mass of component A, or 1 to 30 parts by mass of component B per 1 part by mass of component A, or 1 to 20 parts by mass of component B per 1 part by mass of component A. In another embodiment, the amount of one or more first isoflavones (component A) and one or more amino acids represented by formula (I) or their salts (component B) may be 1 to 50 parts by mass of component A per 1 part by mass of component B, or 1 to 30 parts by mass of component A per 1 part by mass of component B, or 1 to 20 parts by mass of component A per 1 part by mass of component B.

[0062] The dosage of the oral composition can be appropriately determined by a person skilled in the art, depending on the animal species, individual body weight, age, sex, and / or the production capacity of the second isoflavone, for example, per day, per few days, per week, per month, or per year.

[0063] The form of the oral composition is not particularly limited, as long as it is in an orally administered form. Specific administration forms are described in the second embodiment.

[0064] The frequency of administration of the oral composition can be appropriately determined by those skilled in the art depending on the animal species, individual body weight, age, sex, and / or the production capacity of the second isoflavone, for example, it may be administered once a day, several days, once a week, once a month, or once a year. For example, the dose administered once a day, several days, once a week, once a month, or once a year may be divided into multiple doses. It may also be administered optionally when it is desired to promote the production of the second isoflavone and / or to increase the blood, urinary, and / or fecal concentrations of the second isoflavone.

[0065] (Uses) The oral composition according to this embodiment can be used as an oral composition for promoting the production of a second isoflavone and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual. Therefore, it is preferably used for the prevention, treatment, and / or improvement of symptoms of diseases in individuals where any of the above effects are desired.

[0066] In one embodiment, the oral composition is a food composition or a pharmaceutical composition. Specific embodiments will be described in the second embodiment.

[0067] Oral administration of oral compositions includes oral ingestion of food.

[0068] [Second Embodiment: Food Composition, Pharmaceutical Composition] The food composition or pharmaceutical composition according to this embodiment consists of or includes the oral composition according to the first embodiment.

[0069] The food composition and pharmaceutical composition are preferably compositions for promoting the production of a second isoflavone in an individual, and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual.

[0070] According to the oral composition of the first embodiment, it is easy to obtain the effect of promoting the production of the second isoflavone and / or increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual. Therefore, a food composition (food) or pharmaceutical composition (pharmaceutical) containing the oral composition of the first embodiment is preferably used for the prevention, treatment, and / or improvement of symptoms of diseases caused by deficiency of the second isoflavone. Here, "improvement" and "treatment" include the reduction, alleviation, and reduction of disease symptoms, and "prevention" includes protection against the future onset of disease or symptoms and the suppression of its progression.

[0071] Examples of diseases or symptoms resulting from a deficiency of the second type of isoflavone include nonspecific complaints associated with the menstrual cycle, premenstrual syndrome, menopausal symptoms, urogenital disorders such as atrophic vaginitis, osteoporosis, arteriosclerosis, memory impairment, Alzheimer's disease, thrombotic diseases, rough skin, wrinkles, sagging skin, age spots, obesity, muscle atrophy (e.g., disuse muscle atrophy), breast cancer, prostate cancer, high cholesterol, and metabolic syndrome.

[0072] Food compositions and pharmaceutical compositions may be used for human or non-human animals. From the viewpoint of preventing, treating, or improving diseases or symptoms caused by a deficiency of the second isoflavone, the target is preferably female, and more preferably human female.

[0073] The dosage, frequency of administration, and examples and preferred examples of recipients for the food composition or food and the pharmaceutical composition or pharmaceutical are the same as those for the oral composition described in the first embodiment, and can be appropriately determined considering the content of the oral composition contained in the food or pharmaceutical, and the content of one or more first isoflavones and / or one or more amino acids represented by formula (I) or their salts contained in the oral composition.

[0074] A food composition or food, and a pharmaceutical composition or pharmaceutical may be administered to an individual alone, or both may be administered in any combination.

[0075] (Food Composition) In one embodiment, the oral composition according to the first embodiment may be a food composition. The food composition may be a composition that is a food in itself, or a composition that is used as an ingredient in food.

[0076] The food composition according to this embodiment can be used as a food or as an ingredient for the manufacture of food. Food includes not only general food and beverages, but also, for example, nutritional foods and beverages, flavor foods and beverages, nutritional supplements and beverages (supplements), and compositions contained in food additives.

[0077] Food compositions can be prepared in the form of desired foods and beverages (collectively referred to as "foods") by combining one or more first isoflavones or processed products thereof, and / or one or more amino acids represented by formula (I) or salts thereof, or processed products thereof, either as is or in combination with other food and beverage ingredients, additives, one or more food compositions, etc. In one embodiment, it is preferable that the food containing the food composition is a functional food that has effects such as improving undesirable symptoms and / or poor physical condition (including functions related to maintaining and promoting health) in the person who ingests it. Examples of such functional foods include, for example in Japan, general foods and beverages including nutritional supplements, health supplements, nutritional adjustment foods, etc., and health functional foods (including nutrient function foods, foods for specified health uses (FOSHU), and foods with functional claims) for which the function of the food is displayed in accordance with safety and effectiveness standards set by the government.

[0078] The form of the food is not limited, but since the oral composition is administered to an individual and acts to promote the production of a second type of isoflavone in the intestines, it is preferable that it be in a form that can be transferred to the intestines. Although the food composition is an oral composition, from the viewpoint of enabling transfer to the intestines, it is not necessarily limited to being administered via the oral cavity, but also includes methods of direct administration to the intestines via the nasal cavity or pharynx using a tube or the like. In one embodiment, for ease of administration, the food is preferably in a form suitable for oral administration via the oral cavity.

[0079] Non-limiting examples of food forms include supplements such as capsules (soft capsules, hard capsules), tablets, granules, powders, and jellies; beverages such as tea drinks, coffee drinks, energy drinks, fruit juices, carbonated drinks, and lactic acid drinks; and snacks such as gummies, candies, and jellies. Foods may also be general food and beverage products such as soups, processed meat products, processed vegetable products, processed fruit products, seasonings, and concentrated foods. Here, processed products mean products that have been processed and / or cooked from natural ingredients, and include frozen foods, retort foods, canned foods, bottled foods, etc.

[0080] When the target of the food composition is an animal other than a human, the food may be in the form of ordinary animal feed or pet food.

[0081] The food composition may be prepared such that one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are contained in one food product, and by ingesting the food product, one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are administered to the individual simultaneously; or the one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are contained in separate foods, and by ingesting two or more foods simultaneously, separately, or consecutively, one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are administered to the individual. In one embodiment, if the oral composition contained in the food composition is the oral composition (2) according to the first embodiment, the food composition or food product is a food composition or food product containing one or more amino acids represented by formula (I) or salts thereof.

[0082] In one embodiment, if the first isoflavones consist of two or more types of isoflavones, the multiple first isoflavones may be contained in one food product or divided among two or more food products. In one embodiment, if the amino acid or salt thereof represented by formula (I) consists of two or more types of amino acids or salt thereof, the multiple amino acids or salts may be contained in one food product or divided among two or more food products.

[0083] When prepared as two or more food products, each food product can be administered simultaneously, separately at regular time intervals, or consecutively. The two or more food products can also be administered at different times per day. When prepared as two or more food products, each food product can also be administered via different routes. The food composition only needs to be prepared as a food product so that the dosage described in the first embodiment can be administered to an individual, and the dosage per administration may be one food product or two or more food products.

[0084] Here, the food composition or food containing one or more first isoflavones is not limited to those artificially prepared from the oral composition containing one or more first isoflavones according to the first embodiment, but may also be a food composition or food obtained by cooking natural products, including plants containing isoflavones. For example, it may be a cooked product obtained by subjecting plants such as soybeans, kudzu, red clover, alfalfa, and licorice to heat treatment, drying treatment, steaming treatment, etc. If the plant is soybeans, it may be tofu, fried tofu, soy milk, natto, soy sauce, miso, tempeh, etc. For example, if the food composition or food according to this embodiment contains the oral composition (2) according to the first embodiment, consuming these foods as a regular meal or snack, along with consuming the food composition or food containing one or more amino acids represented by formula (I) according to this embodiment or their salts, makes it easier to promote the production of the second isoflavones in the individual, and / or increase the blood, urine, and / or fecal concentrations of the second isoflavones in the individual.

[0085] Foods may also contain food compositions containing functional ingredients in addition to the food composition according to this embodiment. The functional ingredients are not limited to those that are desired to be taken in addition to a normal diet, but it is preferable that they are substances that can exert some nutritional or physiological activity or effect in the subject who ingests them, which is the intended use or purpose of the food containing the food composition.

[0086] When a food composition or food is a Food for Specified Health Uses (FOSHU) or a Food with Function Claims, FOSHU or Food with Function Claims can be preferably used for the prevention, treatment, and / or improvement of symptoms of diseases caused by a deficiency of the second type of isoflavone. For example, the food may have the following functions displayed for the second type of isoflavone: • Maintaining bone components (maintaining strong bones) • Suppressing the decrease in skin moisture (moisture) and elasticity • Alleviating skin dryness • Supporting the maintenance of muscle mass and strength, which are necessary for maintaining the ability to support the body in an independent daily life • Helping to maintain or suppress the decrease in muscle mass and strength • Helping to improve walking ability • Supporting the bending and straightening of the knee joint (smoothness of movement) • Regulating bowel movements • Helping to reduce visceral fat • Helping to improve BMI • Suitable for overweight individuals • Maintaining cognitive function (attention, perception, or recall of recognized things) • Maintaining memory

[0087] (Pharmaceutical Composition) In one embodiment, the oral composition according to the first embodiment may be a pharmaceutical composition. The pharmaceutical composition may be a composition that is a pharmaceutical in itself, or a composition that is used as a material for a pharmaceutical.

[0088] Pharmaceuticals may be prescription drugs, over-the-counter drugs, or quasi-drugs.

[0089] The form of the pharmaceutical is not limited, but since the oral composition is administered to an individual and acts to promote the production of a second type of isoflavone in the intestines, it is preferable that the pharmaceutical is in a form that can be transferred into the intestines. The pharmaceutical can be, for example, a tablet, granule, powder, capsule, emulsion, suspension, syrup, or an injectable preparation such as a sterile solution or suspension. The pharmaceutical composition is an oral composition, but from the viewpoint of enabling transfer into the intestines, it is not necessarily limited to being administered via the oral cavity, but also includes forms in which it is administered directly into the intestines via the nasal cavity or the throat using a tube or the like. In one embodiment, for ease of administration, the pharmaceutical is preferably in a form suitable for oral administration.

[0090] The pharmaceutical composition may be formulated in such a way that one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are compounded into a single drug, and by administering the drug, one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are administered to the individual simultaneously; or, one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof may be compounded into separate drugs, and by administering two or more drugs simultaneously, separately, or sequentially, one or more first isoflavones and one or more amino acids represented by formula (I) or salts thereof are administered to the individual. In one embodiment, if the oral composition included in the pharmaceutical composition is the oral composition (2) according to the first embodiment, the pharmaceutical composition or drug is a pharmaceutical composition or drug containing one or more amino acids represented by formula (I) or salts thereof.

[0091] In one embodiment, if the first isoflavones consist of two or more types of isoflavones, the multiple first isoflavones may be contained in one drug or divided and contained in two or more foods. In one embodiment, if the amino acid or salt thereof represented by formula (I) consists of two or more types of amino acids or salt thereof, the multiple amino acids or salts may be contained in one drug or divided and contained in two or more drugs.

[0092] When prepared as two or more drugs, each drug can be administered simultaneously, separately at regular time intervals, or consecutively. The two or more drugs can also be administered at different rates per day. When prepared as two or more drugs, each drug can also be administered via a different route. The pharmaceutical composition only needs to be prepared as a drug so that the dosage described in the first embodiment can be administered to an individual, and the dosage per administration may be that of one drug or two or more drugs.

[0093] Here, if the pharmaceutical composition or pharmaceutical according to this embodiment contains two or more amino acids or salts thereof represented by formula (I), it may be administered in combination with a food composition or food containing one or more first isoflavones, for example, a food composition or food obtained by cooking natural products such as plants containing isoflavones as described in "Food Compositions."

[0094] A non-limiting list of exemplary embodiments and combinations of exemplary embodiments of the present disclosure is disclosed below: [1] One or more first isoflavones and the following formula (I): An oral composition administered in combination of one or more amino acids or salts thereof represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group]. [2] One or more first isoflavones, and the following formula (I): The oral composition according to [1], comprising one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group], or a salt thereof. [3] comprising one or more first isoflavones, the following formula (I): The oral composition according to [1], administered in combination of one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group]. [4] Formula (I) below: An oral composition according to [1], comprising one or more amino acids or salts thereof represented by formula (I), where R is an amino group, a guanidino group, or a carbamoyl group, and administered in combination with one or more first isoflavones. [5] An oral composition according to any one of [1] to [4] for promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual. [6] An oral composition according to any one of [1] to [6], wherein the first isoflavone is derived from soy. [7] An oral composition according to any one of [1] to [6], wherein the first isoflavone is one or more selected from the group consisting of daidzein, daidzin, malonyldaidzin, and acetyldaidzin. [8] An oral composition according to any one of [1] to [7], wherein the first isoflavone is daidzein. [9] The following formula (I): An oral composition according to any one of [1] to [8], wherein 1 part by mass of one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] is 1 to 50 parts by mass of one or more first isoflavones.

[10] Formula (I) below: An oral composition for promoting the production of a second isoflavone in an individual and / or for increasing the blood, urine, and / or fecal concentration of a second isoflavone in an individual, comprising one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof.

[11] The oral composition according to any one of claims [5] to

[10] , wherein the second isoflavone is equol and / or 5-hydroxyequol.

[12] The following formula (I): An oral composition according to any one of [1] to

[11] , wherein one or more amino acids represented by [formula (I) where R is an amino group, a guanidino group, or a carbamoyl group] are selected from the group consisting of citrulline, ornithine, and arginine or salts thereof.

[13] Formula (I) below: An oral composition according to any one of [1] to

[12] , wherein one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof is citrulline.

[14] An oral composition according to any one of [1] to

[13] , which is a food or pharmaceutical composition.

[15] One or more first isoflavones, and the following formula (I): A method for promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentration of a second isoflavone in an individual, comprising administering in combination one or more amino acids or salts thereof represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] to an individual in need thereof.

[16] Formula (I) below: A method for promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentration of a second isoflavone in an individual, comprising administering one or more amino acids or salts thereof represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] to an individual in need thereof.

[17] The method according to

[15] or

[16] , excluding medical procedures.

[18] One or more first isoflavones and the following formula (I): [In formula (I), R is an amino group, a guanidino group, or a carbamoyl group] A combination of one or more amino acids or salts thereof represented by the following formula (I):

[19] For use in promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual: [In formula (I), R is an amino group, a guanidino group, or a carbamoyl group] One or more amino acids represented by or a salt thereof.

[20] One or more first isoflavones, and the following formula (I): Use in the manufacture of food or pharmaceuticals for promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentration of the second isoflavone in an individual, represented by formula (I) below: [wherein R is an amino group, a guanidino group, or a carbamoyl group].

[21] Formula (I) below: Use in the manufacture of food or pharmaceuticals for promoting the production of a second isoflavone in an individual, and / or increasing the blood, urine, and / or fecal concentration of the second isoflavone in an individual, represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group], one or more amino acids or salts thereof.

[0095] The present disclosure will be further illustrated by the following examples, but these examples will not limit the interpretation of the present disclosure.

[0096] [Example 1] (In vitro promotion of equol production by citrulline or arginine) 10 mL of BHI medium (manufactured by Nissui Pharmaceutical Co., Ltd.) was dispensed into a 100 mL vial, which was then sealed with a butyl rubber stopper and an aluminum cap. After purging the gas phase with nitrogen, the vial was heat-sterilized in an autoclave at 121°C for 15 minutes. Asaccharobacter ceratus glycerol stock solution was inoculated into this medium to a concentration of 1% (v / v), and after purging the gas phase with 100% hydrogen, pre-culture was performed at 37°C and 200 spm for 18 hours.

[0097] 10 mL of BHI medium was dispensed into 100 mL vials, and daidzein powder (manufactured by LC Laboratories®) was added to a concentration of 1 g / L. Then, citrulline or arginine was added to each vial as follows: (1) 0.5 g / L-arginine (manufactured by Kyowa Hakko Bio Co., Ltd.) (2) 1.5 g / L-arginine (manufactured by Kyowa Hakko Bio Co., Ltd.) (3) 5 g / L-arginine (manufactured by Kyowa Hakko Bio Co., Ltd.) (4) 0.5 g / L-citrulline (manufactured by Kyowa Hakko Bio Co., Ltd.) (5) 1.5 g / L-citrulline (manufactured by Kyowa Hakko Bio Co., Ltd.) (6) 5 g / L-citrulline (manufactured by Kyowa Hakko Bio Co., Ltd.) Afterwards, the pH of these media was adjusted to 7.5 with 1N sodium hydroxide aqueous solution (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.).

[0098] A control condition was used: BHI medium (manufactured by Nissui Pharmaceutical Co., Ltd.) to which only daidzein powder (manufactured by LC Laboratories) was added to a concentration of 1 g / L, without the addition of citrulline or arginine.

[0099] A 200 mL vial containing the above-mentioned BHI medium containing citrulline or arginine was sealed with a butyl rubber stopper and an aluminum cap, and after purging the gas phase with nitrogen, it was heat-sterilized in an autoclave at 121°C for 15 minutes.

[0100] After heat sterilization, the above pre-culture solution was inoculated into the culture medium at a concentration of 1% (v / v), the gas phase was replaced with 100% hydrogen, and the culture was incubated at 37°C for 24 hours. The culture medium was centrifuged after incubation, the supernatant was collected, diluted as appropriate, and HPLC analysis was performed to measure the amount of equol produced. The HPLC analysis conditions were as follows: Column: Phenomenox Luna 5uC18, 2.0 mm × 150 mm (Shimadzu GLC) Mobile phase: Water / methanol [55:45, v / v] Flow rate: 0.2 mL / min Column temperature: 40°C Detection: UV 280 nm Retention time: Daidzein 19.6 min, Equol 25.6 min.

[0101] Figure 1 shows the equol yield at 24 hours of culture. The average equol yield (%) is shown with daidzein added as the substrate set to 100% (n=2). Under control conditions without citrulline or arginine, 40% of equol was produced, while in the medium with citrulline or arginine added, more than 70% of equol was produced, indicating an increase in equol production. Furthermore, the amount of equol produced increased with increasing amounts of citrulline or arginine added.

[0102] [Example 2] (Promotion of equol production by citrulline or arginine in vivo (rats)) Daidzein (manufactured by LC Laboratories) and L-citrulline (manufactured by Kyowa Hakko Bio Co., Ltd.) or L-arginine hydrochloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were suspended in predetermined amounts in a 0.5% by mass aqueous solution of sodium carboxymethylcellulose (manufactured by Kanto Chemical Co., Ltd.) to prepare daidzein suspension, daidzein and citrulline mixed suspension, and daidzein and arginine hydrochloride mixed suspension for forced oral administration. The base feed used was AIN-93M (Oriental Yeast Co., Ltd.), in which soybean oil was replaced with linseed oil.

[0103] Six-week-old female SD rats (SPF, manufactured by Nippon Crea Co., Ltd.) were used in groups of six and were allowed free access to basal diet AIN-93M and water for seven days during the acclimatization period. Day 0 was set at the end of the acclimatization period, and each group was force-administered either a daidzein and citrulline suspension or a daidzein and arginine hydrochloride suspension prepared above for 14 days. The control group was force-administered a suspension containing only daidzein for 14 days. The force-administered dose of the suspension was 10 mL / kg (body weight) per day for all rats. Basal diet and water were allowed free access throughout the administration period. Furthermore, all rats were housed individually in cages from the acclimatization period to the end of administration.

[0104] The experimental groups were as follows: (1) Control group (administered only 20 mg of daidzein / rat / day) (2) Low-dose citrulline group (20 mg of daidzein / rat / day and 26 mg of citrulline / rat / day) (3) High-dose citrulline group (20 mg of daidzein / rat / day and 260 mg of citrulline / rat / day) (4) Low-dose arginine group (20 mg of daidzein / rat / day and 31 mg of arginine hydrochloride / rat / day)

[0105] The above administration was performed once daily for 14 consecutive days. Fecal and urine samples were collected at four points: before administration, 4 days after administration, 8 days after administration, and after the end of the entire administration period (15th day after administration). At these points, samples were collected from immediately after administration for 24 hours. Furthermore, on the 15th day after administration, after the completion of fecal and urine collection, blood was collected from the posterior vena cava to obtain plasma from all subjects.

[0106] Quantitative analysis of equol in rat urine and plasma was performed by deconjugating conjugated equol present in urine and plasma with β-glucuronidase and allylsulfatase, followed by measurement using HPLC. 7.5 U of β-glucuronidase and 15 U of allylsulfatase (Roche) were added to 250 μL of urine, and 15 U of β-glucuronidase and 30 U of allylsulfatase (Roche) were added to 500 μL of plasma. After incubation at 37°C for 2 hours to free equol, it was extracted with ethyl acetate (Fujifilm Wako Pure Chemical Industries, Ltd.) and measured using HPLC.

[0107] Quantitative analysis of equol in rat feces was performed by extracting it from the feces using the method described below, followed by measurement using HPLC. Approximately 90 mg of feces was mixed with 1 mL of 70% methanol aqueous solution (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), ground and suspended using beads, and then centrifuged. The supernatant was collected, and the amount of equol in the supernatant was measured using HPLC. The HPLC analysis conditions were as follows: Column: Phenomenox Luna 5uC18, 2.0 mm × 150 mm (Shimadzu GLC) Mobile phase: Water / methanol [55:45, v / v] Flow rate: 0.2 mL / min Column temperature: 40°C Detection: UV 280 nm Retention time: Daidzein 19.6 min, Equol 25.6 min.

[0108] Figure 2 shows the results of the analysis of fecal samples collected after the completion of the entire administration period. Equol content is shown as the mean + / - standard deviation of the amount of equol in the total urine and fecal volume of each individual (n=6), calculated based on the amount of equol in urine (250 μL) and feces (90 mg) measured for each individual. Compared to the control group administered only daidzein, equol production increased in the citrulline low-dose group, citrulline high-dose group, and arginine low-dose group, which were administered in combination with daidzein or arginine.

[0109] Figure 3 shows the analysis results of urine samples collected after the end of the entire administration period. Equol content is shown as the mean + / - standard deviation (n=6) calculated from the equol concentration and urine volume in the collected urine. Compared to the control group administered daidzein alone, equol production increased in the high-dose citrulline administration group, which was administered in combination with daidzein.

[0110] Figure 4 shows the results of the plasma sample analysis. Equol content is shown as the mean + / - standard deviation calculated from the plasma equol concentration and plasma volume (n=6). Plasma equol concentration increased in the high-dose citrulline administration group compared to the control group administered only daidzein, indicating increased equol production.

[0111] [Example 3] (Evaluation of daidzein dosage for promoting equol production in vivo (mice) by combination with citrulline) Daidzein (manufactured by LC Laboratories) and L-citrulline (manufactured by Kyowa Hakko Bio Co., Ltd.) were suspended in predetermined amounts in a 0.5% by mass aqueous solution of sodium carboxymethylcellulose (manufactured by Kanto Chemical Co., Ltd.) to prepare a daidzein suspension and a mixed suspension of daidzein and citrulline for forced oral administration. The basal feed used was AIN-93M (Oriental Yeast Co., Ltd.), in which soybean oil was replaced with linseed oil.

[0112] Eight-week-old C57BL / 6J mice (SPF, manufactured by Nippon SLC Co., Ltd.) were used in groups of three and allowed free access to basal diet AIN-93M and water for one week of acclimatization. Day 0 was set at the end of the acclimatization period, and each group was force-administered the daidzein suspension prepared above for seven days. Subsequently, a daidzein and citrulline mixed suspension was force-administered for 14 days. The same dose of daidzein was administered to each individual mouse, both when daidzein alone was administered and when the daidzein and citrulline mixed suspension was administered. The force-administered amount of the mixed suspension was 300 μL per day for all mice. Basal diet and water were allowed free access throughout the administration period. Furthermore, all mice were housed individually in cages from the acclimatization period to the end of administration.

[0113] The experimental groups were as follows: (1) High-dose daidzein group (daidzein 10 mg / mouse / day and citrulline 42 mg / mouse / day) (2) Medium-dose daidzein group (daidzein 5 mg / mouse / day and citrulline 42 mg / mouse / day) (3) Low-dose daidzein group (daidzein 2.5 mg / mouse / day and citrulline 42 mg / mouse / day) The above administrations were carried out once a day for 21 consecutive days. Urine samples were collected at three points: before the start of administration, on the 8th day after the start of administration (after the completion of daidzein-only administration), and after the completion of the entire administration period (22nd day after the start of administration).Quantitative analysis of equol in mouse urine was performed by deconjugating conjugated equol present in the urine with β-glucuronidase and allylsulfatase using the method described below, and then measuring it using HPLC. 30 μL of urine was mixed with 0.09 U of β-glucuronidase and 0.18 U of allylsulfatase (Roche), and incubated at 37°C for 2 hours to release equol. The mixture was then extracted with ethyl acetate (Fujifilm Wako Pure Chemical Industries, Ltd.) and measured using HPLC. HPLC analysis was performed under the analytical conditions described in Example 2.

[0114] Figure 5 shows the measured equol concentrations (mean + / - standard deviation, n=3) for each group. Comparing the urinary equol concentrations collected after the completion of daidzein-only administration with those collected after administration of a mixed suspension of daidzein and citrulline, it was found that administering the mixed suspension of daidzein and citrulline increased the urinary equol concentration, regardless of the amount of daidzein administered.

[0115] The oral composition of this embodiment can be used to promote the production of a second isoflavone in an individual and / or to increase the blood, urine, and / or fecal concentrations of the second isoflavone in an individual, and has industrial applicability.

Claims

1. One or more types of first isoflavones, and the following formula (I): An oral composition administered in combination of one or more amino acids or salts thereof represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group].

2. One or more types of first isoflavones, and the following formula (I): The oral composition according to claim 1, comprising one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof.

3. Contains one or more types of the first isoflavone, and the following formula (I): The oral composition according to claim 1, administered in combination of one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof.

4. The following formula (I): The oral composition according to claim 1, comprising one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof, which is administered in combination with one or more first isoflavones.

5. The oral composition according to claim 1 for promoting the production of a second isoflavone in an individual, and / or for increasing the blood, urine, and / or fecal concentration of the second isoflavone in an individual.

6. The oral composition according to any one of claims 1 to 5, wherein the first isoflavone is derived from soybeans.

7. The oral composition according to any one of claims 1 to 5, wherein the first isoflavone is one or more selected from the group consisting of daidzein, daidzin, malonyldaidzin, and acetyldaidzin.

8. The oral composition according to any one of claims 1 to 5, wherein the first isoflavone is daidzein.

9. The following formula (I): The oral composition according to any one of claims 1 to 5, wherein the composition is 1 to 50 parts by mass of one or more first isoflavones with respect to 1 part by mass of one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group].

10. The following formula (I): An oral composition comprising one or more amino acids represented by formula (I) [wherein R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof, for promoting the production of a second isoflavone in an individual, and / or for increasing the blood, urine, and / or fecal concentrations of the second isoflavone in an individual.

11. The oral composition according to claim 5 or 10, wherein the second isoflavone is equol and / or 5-hydroxyequol.

12. The following formula (I): The oral composition according to claim 1 or 10, wherein one or more amino acids represented by [formula (I) where R is an amino group, a guanidino group, or a carbamoyl group] are selected from the group consisting of citrulline, ornithine, and arginine, or salts thereof.

13. The following formula (I): The oral composition according to claim 1 or 10, wherein one or more amino acids represented by [formula (I) where R is an amino group, a guanidino group, or a carbamoyl group] or a salt thereof is citrulline.

14. An oral composition according to claim 1 or 10, which is a food or pharmaceutical composition.

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