WO2022158595A1

WO2022158595A1 - Isoflavone absorption promoter and skin moisture reduction inhibitor

Info

Publication number: WO2022158595A1
Application number: PCT/JP2022/002469
Authority: WO
Inventors: 彩加川端; 俊也丸尾; 利雄鈴木; 良太赤木; 裕一卯川; 健一大江
Original assignee: フジッコ株式会社; 株式会社ダイセル
Priority date: 2021-01-25
Filing date: 2022-01-24
Publication date: 2022-07-28
Also published as: JPWO2022158595A1; JP7166500B1

Abstract

The purpose of the present invention is to provide a novel agent for promoting the absorption of isoflavone into the body. The present invention provides an isoflavone absorption promoter, the isoflavone absorption promoter being an agent that contains a lactobionic acid.

Description

Isoflavone absorption enhancer and skin moisture reduction inhibitor

The present invention relates to an isoflavone absorption enhancer, and relates to suppression of a decrease in skin moisture content by an isoflavone absorption enhancement action.

Isoflavones, which are abundant in soy products, are also called phytoestrogens due to their similarity in chemical structure to female hormones (estrogen). It is known to be effective in relieving, maintaining bone density, and preventing breast and prostate cancer, hypercholesterolemia, and heart disease.

Isoflavones contained in soybeans rarely exist in the form of aglycones, genistein and daidzein, except for fermented foods, and most of them exist as glycosides such as genistin and daidzin. However, isoflavones are not absorbed from the intestinal tract as glycosides, but can be hydrolyzed into aglycones by β-glycosidase produced by intestinal bacteria and absorbed in the intestinal tract.

Methods for enhancing the beneficial effects of isoflavones by enhancing the absorption of isoflavones have been investigated. For example, as a technique for promoting the absorption of polyphenol compounds containing isoflavones into the body, lactic acid bacteria products containing polysaccharides ( Patent Document 1), a culture of black koji mold (Patent Document 2), and the use of citrate or citric acid (Patent Document 3) have been proposed.

International Publication No. 2018/169027 JP 2018-052889 A JP 2010-037258 A

The purpose of the present invention is to provide a new agent that promotes the absorption of isoflavones into the body.

The present invention relates to [1] to [9] exemplified below.
[1] An isoflavone absorption enhancer containing lactobionic acids.
[2] A skin condition-improving agent containing lactobionic acids and having an isoflavone absorption-enhancing effect.
[3] The agent of [2], which is an agent for suppressing a decrease in skin moisture content, an agent for suppressing transepidermal water loss, or an agent for improving skin viscoelasticity.
[4] The agent according to any one of [1] to [3], which is used for non-equol producers.
[5] The agent according to any one of [1] to [4], further comprising isoflavones.
[6] The agent according to [5], wherein the isoflavones are derived from soybeans.
[7] The agent according to any one of [1] to [6], which is an oral agent.
[8] The agent according to any one of [1] to [7], which is a food or drink composition.
[9] Use of lactobionic acids in the production of isoflavone absorption enhancers.

According to the present invention, it is possible to provide a new agent that promotes absorption of isoflavones into the body. According to the present invention, the estrogenic activity of isoflavones can be effectively enhanced by promoting the absorption of isoflavones into the body even for non-equol producers who cannot expect the estrogen-like activity of equol.

1 is a graph showing isoflavone concentrations of all subjects (total) in Test Example 1. FIG. 1 is a graph showing the total concentrations of isoflavones and equol of all subjects (total) in Test Example 1. FIG. 4 is a graph showing the stratum corneum moisture content of cheeks of all subjects (total) in Test Example 1. FIG. 1 is a graph showing isoflavone concentrations in non-equol producers in Test Example 1. FIG. 4 is a graph showing the total concentrations of isoflavones and equol in non-equol producers in Test Example 1. FIG. 4 is a graph showing the moisture content of the stratum corneum in the cheeks of non-equol producers in Test Example 1. FIG. 1 is a graph showing isoflavone concentrations in equol producers in Test Example 1. FIG. 1 is a graph showing the total concentrations of isoflavones and equol in equol producers in Test Example 1. FIG. 4 is a graph showing the moisture content of the stratum corneum of the cheeks of equol producers in Test Example 1. FIG. 3 is a graph showing isoflavone concentrations of all subjects (total) in Test Example 2. FIG. 4 is a graph showing isoflavone concentrations in equol producers in Test Example 2. FIG. 4 is a graph showing isoflavone concentrations in non-equol producers in Test Example 2. FIG. 4 is a graph showing the stratum corneum water content of the left cheek of all subjects (total) in Test Example 2. FIG. 4 is a graph showing the stratum corneum water content of the left cheek of non-equol producers in Test Example 2. FIG. 4 is a graph showing the stratum corneum water content of the left shin of all subjects (total) in Test Example 2. FIG. 4 is a graph showing the stratum corneum water content of the left shin of non-equol producers in Test Example 2. FIG. 10 is a graph showing percutaneous water loss on the left cheek of all subjects (total) in Test Example 2. FIG. 4 is a graph showing the amount of transepidermal water loss on the left cheek of an equol non-producer in Test Example 2. FIG. 10 is a graph showing percutaneous water loss of the left shin of all subjects (total) in Test Example 2. FIG. 4 is a graph showing percutaneous water loss in the left shin of non-equol producers in Test Example 2. FIG. 10 is a graph showing the net elasticity (R5) of the left cheek of all subjects (total) in Test Example 2. FIG. 10 is a graph showing the left cheek net elasticity (R5) of non-equol producers in Test Example 2. FIG. 10 is a graph showing the left cheek overall body elasticity (R2) of all subjects (total) in Test Example 2. FIG. 4 is a graph showing the left cheek gross elasticity (R2) of non-equol producers in Test Example 2. FIG. 10 is a graph showing the return rate (R7) of the left cheek of all subjects (total) in Test Example 2. FIG. 10 is a graph showing the return rate (R7) of the left cheek of non-equol producers in Test Example 2. FIG. 2 is a graph showing unrecovered extensibility/retraction ability (R1) of the left cheek of all subjects (total) in Test Example 2. FIG. 4 is a graph showing unrecovered extensibility/retraction ability (R1) of the left cheek of non-equol producers in Test Example 2. FIG. FIG. 10 is a graph showing the scores of bags under the eyes of all subjects (total) in Test Example 2. FIG. 10 is a graph showing evaluation points for bags under the eyes of non-equol producers in Test Example 2. FIG.

<Isoflavone absorption enhancer>
The isoflavone absorption enhancer of the present invention (hereinafter also simply referred to as "isoflavone absorption enhancer") contains lactobionic acid. An isoflavone absorption enhancer can promote absorption of isoflavones into the body of a subject by administering it to the subject.

Isoflavones are known to exhibit estrogenic activity. Estrogen is a type of female hormone that not only relieves menopausal symptoms and regulates various functions of the female body, such as breast, skin, and bone metabolism, but also reproductive function, brain/central nervous system function, and circulatory system (cardiovascular system). ) function, lipid metabolism (cholesterol and triglyceride) is known to have an action to adjust and improve. In general, especially in women, the amount of estrogen secreted decreases after reaching the age of 40. When the amount of estrogen secreted decreases, symptoms such as menopausal symptoms, forgetfulness and depression symptoms, dyslipidemia, breast atrophy, skin atrophy, and bone loss may occur. An isoflavone absorption enhancer promotes the absorption of isoflavones into the body, and the estrogenic activity of isoflavones can be expected to prevent or alleviate the above symptoms.

Isoflavone absorption enhancers are preferred to be administered to women because their effects are desired by women. A preferred embodiment is administration to women whose skin tends to be dry, and a preferred embodiment is administration to non-equol producers. This is because non-equol producers prefer the effect of the present invention that absorption of isoflavones into the body by the isoflavone absorption enhancer is more desirable than equol producers.

Daidzein, one of the isoflavones, is metabolized into equol, which has strong estrogen-like activity and antioxidant activity, and O-desmethylangolensin, which has no activity. The presence of equol-producing intestinal bacteria is essential for this metabolism.

Since equol has stronger estrogen-like activity than the original daidzein, it is expected to have beneficial effects, but there are individual differences in equol production. and those who cannot produce equol (non-equol producers). The individual differences are thought to be due to differences in intestinal microflora.

The proportion of equol producers has been reported in many studies, and is said to be about 50% for Japanese and 20-30% for Westerners. There is a problem that the beneficial effects of isoflavones cannot be sufficiently and efficiently enjoyed by non-equol-producing individuals who do not have equol in their blood. Therefore, a preferred embodiment is one in which the isoflavone absorption enhancer is administered to non-equol producers.

　The isoflavone absorption promoting effect can be evaluated by measuring changes in the concentration of isoflavones in the urine or blood of the subject. The present inventors have found in the test examples described later that administration of lactobionic acids together with isoflavones can increase the concentration of isoflavones in urine compared to administration of isoflavones alone. confirmed.

In the present invention, lactobionic acids include lactobionic acid or salts thereof, and including lactobionic acids means including at least one compound that is a lactobionic acid. Lactobionic acid is a disaccharide and sugar acid composed of gluconic acid and galactose. Salts of lactobionic acid include salts with alkali metals such as sodium and potassium, alkaline earth metals such as calcium, magnesium and iron. Lactobionic acid is known to form a chelate when forming salts with polyvalent metals such as iron, magnesium, and calcium.

The lactobionic acids may be those produced by a known method, or may be commercially available products. Methods for producing lactobionic acid include a method in which microorganisms such as Pseudomonas graveolens having lactose dehydrogenase activity act on lactose as a substrate; A method of producing lactose by oxidizing lactose using microorganisms of the genus Acinetobacter and the genus Burkholderia is known.

As a method for producing a salt of lactobionic acid, a method of preparing by normal salt conversion reaction such as neutralization of lactobionic acid, a method of producing lactobionic acid from lactose by a biotransformation reaction using enzymes or microorganisms, and calcium carbonate etc. are added to the reaction system. A method of adding in advance and the like can be mentioned.

The lactobionic acids contained in the isoflavone absorption enhancer may be solid such as crystals, powders, or granules, or may be dissolved in a liquid.

The dosage of the isoflavone absorption enhancer varies depending on the sex, age, body weight, diet, mode of administration, symptoms, degree of expected effect, etc. of the subject to be administered. is 150 mg or more, more preferably 200 mg or more, and still more preferably 250 mg or more.

Subjects to whom the isoflavone absorption enhancer is administered are not limited to the above-mentioned females (humans), but are preferably individuals who are expected to effectively utilize isoflavones in the body, and non-human mammals instead of humans. It can be performed on animals.

The isoflavone absorption enhancer may further contain isoflavones. Hereinafter, the isoflavone absorption enhancer containing isoflavones is also referred to as "isoflavones-containing isoflavone absorption enhancer". The isoflavone absorption enhancer can promote absorption into the body of isoflavones that have already been ingested by the administration subject or that will be ingested later by the administration subject due to the action of isoflavone absorption enhancement by lactobionic acids. When the isoflavone absorption enhancer contains isoflavones together with lactobionic acids, the isoflavones contained therein are also subject to absorption promotion, and a further increase in the concentration of isoflavones in the body can be expected. For the same reason, the isoflavone absorption enhancer is preferably used together with a food containing isoflavones or in one hour before and after ingesting a food containing isoflavones.

"Isoflavones" is a general term for compounds whose basic skeleton is the compound represented by the following formula. In the present specification, containing isoflavones means containing at least one compound that is isoflavones.

The isoflavones are preferably soybean-derived isoflavones (hereinafter, "soybean isoflavones"). Soy isoflavones are known to include compounds having the above basic skeleton (soy isoflavone aglycones), glycosides (soy isoflavone glycosides) in which sugar is bound thereto, and acetylated and malonylated glycosides. It is The term "soybean isoflavones" in the present invention includes without distinction these soybean isoflavone aglycones, soybean isoflavone glycosides, and their acetylated and malonylated forms. Specifically, soy isoflavone aglycones include genistein, daidzein, and glycitein. Soy isoflavone glycosides include genistin, daidzin, and glycitin. Acetylated soybean isoflavone glycosides include acetylgenistin, acetyldaidzin, and acetylglycitin, and malonylated soybean isoflavone glycosides include malonylgenistin, malonyldaidzin, and malonylglycitin. These soy isoflavones may be used singly or in combination of two or more. Further, in the present invention, soy isoflavones may be those refined from soybeans, but may also be crudely refined products such as those extracted from soybeans (extracts), pulverized or shredded soybeans. etc. may be used. Methods for purifying or extracting isoflavones from soybeans are known, and in the present invention, purified products or extracts of soybean isoflavones obtained by known methods can be used. Commercially available soy isoflavones can also be used.

The content of isoflavones contained in isoflavone absorption enhancers containing isoflavones is not particularly limited in the case of normal soybean processed foods, except for foods in which isoflavones are concentrated or enriched. do not have. On the other hand, in the case of the isoflavone-concentrated or fortified food, the content of isoflavones contained in the isoflavone-containing isoflavone absorption enhancer should be is adjusted to be 30 mg or less in terms of mass of isoflavone aglycones.

Examples of administration routes of isoflavone absorption enhancers and isoflavone absorption enhancers containing isoflavones include parenteral administration such as oral administration and enteral administration. Isoflavone absorption enhancers are not particularly restricted according to their uses (drugs, quasi-drugs, foods and drinks [including health functional foods such as specified health foods and nutritional functional foods, and supplements]). do not have.

(oral agent)
Oral preparations of the present invention include, for example, animal drugs, quasi-drugs, pharmaceuticals, therapeutic drugs, prophylactic drugs, and the like.

In the present invention, the absorption of isoflavones can be promoted by administering the above-mentioned doses to the administration subject. In that case, the active ingredients of lactobionic acids, or lactobionic acids and isoflavones can be used as they are or in combination with pharmaceutical carriers. They can be mixed and administered in consideration of the amount to be administered, the condition of the administration subject (eg, patient), and the like.

Specific examples of oral agents include tablets, capsules, granules, powders, fine granules, chewable tablets, pills, lozenges, sublingual tablets, emulsions, suspensions, jelly agents, syrups, liquid agents, Examples include ampoules, gum formulations, drop formulations, and the like.

Furthermore, the present invention also includes a form in which the active ingredients of lactobionic acids and isoflavones are separately formulated and mixed at the time of administration, or taken simultaneously at the time of administration.

(Beverage composition)
The food and drink composition of the present invention includes, for example, foods (including foods with nutrient function claims, foods for specified health uses, etc.), beverages, nutritional supplements, nutrients, feeds, and the like.

When the food and drink composition of the present invention is a nutritional supplement or nutritional supplement, its dosage form includes, for example, tablets, capsules, granules, powders, fine granules, chewable tablets, pills, Lozenges, sublingual tablets, jellies, syrups, liquids and the like are included.

　Isoflavone absorption enhancers (including isoflavone absorption enhancers containing isoflavones) can be provided and sold as foods and drinks that indicate uses such as isoflavone absorption enhancement. Such indications are not particularly limited, but include ``improvement of isoflavone absorption'', ``can be expected to increase isoflavone concentration'', ``contribution to women's health and beauty'', ``relief of menopausal symptoms'', `` Maintains bone density, improves skin condition, improves lipid metabolism, maintains skin moisture, maintains skin elasticity, improves wrinkles, and enhances skin barrier function. ” and the like. The act of "displaying" includes all acts for informing consumers of the above-mentioned use. Regardless of the medium, etc., all of them fall under the act of "display" of the present invention. An isoflavone absorption enhancer can be provided and sold with a label that reminds and suggests that a "non-equol producer" is a preferred intake.

It is preferable that the content of the display is a display approved by the government (for example, a display that is approved based on various systems established by the government and performed in a manner based on such approval). In addition, it is preferable to attach such display contents to packaging, containers, catalogs, pamphlets, POP and other advertising materials at sales sites, other documents, and the like.

Labeling includes labeling as health food, functional food, enteral nutrition food, food for special dietary use, food with health claims, food for specified health use, food with nutrient function claims, food with function claims, and quasi-drugs. mentioned. Among these, in particular, labeling approved by the Consumer Affairs Agency, for example, labeling approved by a system related to food for specified health use, food with nutrient function claims, or food with function claims, or a system similar thereto can be mentioned. Specifically, labeling as a food for specified health use, labeling as a food for specified health use with certain conditions, labeling as a food with function claims, labeling to the effect that it affects the structure and function of the body, labeling to reduce the risk of disease, and scientific labeling. functional labeling based on rationale, etc.

(Use of isoflavone absorption enhancer)
The present invention provides the use (method) of lactobionic acids in the production of isoflavone absorption enhancers (including isoflavone absorption enhancers containing isoflavones). The method is a method of using lactobionic acids for imparting an effect of promoting absorption of isoflavones to oral preparations and food and drink compositions, and the methods target lactobionic acids, or lactobionic acids and isoflavones. It can be carried out by blending in oral agents and food and drink compositions to be used. The details of the method are as described above.

<Skin Moisture Reduction Inhibitor, Transepidermal Water Loss Inhibitor, Skin Elasticity Improver>
The skin moisture reduction inhibitor of the present invention (hereinafter also simply referred to as "skin moisture reduction inhibitor") contains lactobionic acids. When administered to a subject, the agent for suppressing the decrease in skin moisture content can suppress the decrease in the subject's skin moisture content by promoting the absorption of isoflavones into the body of the subject. Suppression of reduction in skin moisture content includes, for example, improvement of stratum corneum (or stratum corneum) moisture content (e.g., suppression of decrease in stratum corneum moisture content, increase in moisture content of stratum corneum), and improvement of stratum corneum moisture content. Examples of skin improvement include improvement of skin moisturizing properties, improvement of flexibility, improvement of skin texture, improvement of skin barrier function, improvement of wrinkles, and the like. The stratum corneum moisture content can be measured, for example, by measuring the capacitance of the skin surface using Corneometer (registered trademark) CM825 (Courage+Khazaka electronic GmbH).

The transepidermal water loss inhibitor of the present invention (hereinafter also simply referred to as "transepidermal water loss inhibitor") contains lactobionic acid. By administering the transepidermal water loss inhibitor to a subject, it is possible to suppress the amount of water evaporated through the skin of the subject by the action of promoting the absorption of isoflavones into the body of the subject. Improvements in skin caused by suppressing the amount of water that transpires through the skin include, for example, improvement in skin moisturizing properties, improvement in flexibility, improvement in skin texture, improvement in skin barrier function, and improvement in wrinkles. mentioned. Transepidermal water loss (TEWL) measurements are performed using, for example, a Tewameter® TM300 (Courage+Khazaka electronic GmbH) through two sets of highly sensitive temperature and humidity sensors located at the tip of the probe It can be done by measuring the temperature difference and humidity difference of the moisture.

The skin viscoelasticity-improving agent of the present invention (hereinafter also simply referred to as "skin viscoelasticity-improving agent") contains lactobionic acid. When administered to a subject, the skin viscoelasticity improving agent can improve the viscoelasticity and flexibility of the subject's skin by promoting the absorption of isoflavones into the body of the subject. . Improvement in skin viscoelasticity can be judged by focusing on, for example, net elasticity (R5), total body elasticity (R2), return rate (R7), unrecovered extensibility/retraction ability (R1), and the like. Net elasticity (R5), total body elasticity (R2), and return rate (R7) are values that decrease with age. be able to. On the other hand, since the unrecovered extensibility/retraction capacity (R1) is a value that increases with age, it can be judged that the increase in the value is suppressed or the value is decreased, thereby improving. Measurement of skin viscoelasticity can be performed, for example, using a Cutometer (registered trademark) MPA580 (Courage+Khazaka electronic GmbH, probe diameter 2 mm).

As mentioned above, isoflavones are known to exhibit estrogen-like activity, and estrogen is known to have the effect of regulating skin functions. Specifically, it has been reported that estrogen activates skin fibroblasts when bound to estrogen receptors in the body and promotes the production of collagen and hyaluronic acid (Bentley JP, et al. J Invest Dermatol. 87( 5):668-73:1986, et al.). The present inventors have found in the test examples described below that administration of lactobionic acids together with isoflavones can improve the concentration of isoflavones in urine compared to administration of isoflavones alone. That is, the fact that the concentration of isoflavones in the blood increases, the fact that the decrease in the skin moisture content can be suppressed, the amount of transepidermal water loss can be suppressed, and the viscoelasticity of the skin can be improved. ,It was confirmed. Even in equol non-producers who cannot efficiently enjoy the beneficial effects of isoflavones, the concentration of isoflavones in the blood is significantly increased, and it is possible to suppress the decrease in skin moisture content and the amount of transepidermal water loss. It was confirmed that it is possible to improve the viscoelasticity of the skin. Based on the estrogenic activity of isoflavones and the known effects of estrogen on skin function, at least some of the effects that can increase skin hydration, at least some of the effects that can reduce transepidermal water loss. It can be speculated that a part, and at least a part of the effect of improving the viscoelasticity of the skin, is brought about by the action of promoting the absorption of isoflavones.

The skin to be improved by the skin hydration inhibitor, the transepidermal water loss inhibitor, and the skin viscoelasticity improving agent is not particularly limited. Examples include arms, elbows, backs of hands, fingertips, feet, knees, shins, heels, necks, armpits, and backs.

The skin water content reduction inhibitor, the transepidermal water loss inhibitor, and the skin viscoelasticity improving agent may be the above-mentioned isoflavone absorption enhancers themselves, and further contain the isoflavone absorption enhancers and other ingredients. Alternatively, the other ingredients may include other ingredients known to suppress a decrease in skin moisture content. Other ingredients include astaxanthin, placenta, N-acetylglucosamine, ceramide, hyaluronic acid, collagen, elastin, vitamin C, coenzyme Q10, lactic acid bacteria, and the like. An isoflavone absorption enhancer that can be used as a skin moisture reduction inhibitor, a transepidermal water loss inhibitor, and a skin viscoelasticity improving agent, and a skin moisture reduction inhibitor, a transepidermal water evaporation inhibitor, and a skin viscoelasticity improving agent With respect to the isoflavone absorption enhancer that can be contained in the above description of the isoflavone absorption enhancer applies.

A food and drink composition for suppressing a decrease in skin moisture content can be provided and sold as a food and drink labeling the use such as suppression of a decrease in skin moisture content. Although such labeling is not particularly limited, it is possible to "suppress the decrease in skin moisture content", "can be expected to have the effect of suppressing the decrease in skin moisture content due to the absorption promoting action of isoflavones", and "contribution to women's health and beauty". , “leads to fresh skin”, “helps prevent dry skin”, “maintains skin condition”, “maintains skin moisture”, and the like.

The food and drink composition for suppressing transepidermal water loss can be provided and sold as a food and drink labeling the use such as suppression of transepidermal water loss. Such indications are not particularly limited, but include ``enhances skin barrier function'', ``suppresses transepidermal moisture loss'', ``isoflavone absorption promotion action can be expected to suppress decrease in skin moisture content'', `` Contribution to women's health and beauty", "Lead to fresh skin", "Help prevent skin from drying out", "Maintain skin condition", "Keep skin moist", and the like.

Food and drink compositions for improving skin viscoelasticity can be provided and sold as food and drink with indications of uses such as improving skin viscoelasticity. Such labeling is not particularly limited, but "maintains skin elasticity," "improves skin viscoelasticity," "improves skin flexibility," "contributes to women's health and beauty," and "makes skin elastic." guide", "maintain skin condition", and the like.

The act of "displaying" includes all acts for informing consumers of the above-mentioned use. Regardless of the medium, etc., all of them fall under the act of "display" of the present invention. The food and drink composition for suppressing skin moisture can be provided and sold with a label that reminds and suggests that the preferred ingestor is an “equol non-producer”.

<Skin improvement agent>
The skin-improving agent of the present invention (hereinafter also simply referred to as "skin-improving agent") contains lactobionic acids. When administered to a subject, the skin-improving agent can improve the skin condition of the subject by promoting the absorption of isoflavones into the body of the subject.

Improvement of skin condition means improvement of skin condition that can be confirmed based on measurement, such as suppression of decrease in skin moisture content, suppression of transepidermal water evaporation, improvement of skin viscoelasticity, and the like. or improvement in skin condition as confirmed by the senses.

Examples of skin-improving agents include the above-mentioned skin moisture reduction inhibitors, transepidermal water loss inhibitors, and skin elasticity improving agents. In addition, as skin improvement, for example, improvement of worrisome pores, improvement of rough texture, improvement of rough skin, improvement of worrisome spots and freckles , Poor complexion is improved, lack of transparency in the skin is improved, dullness of the skin is improved, dryness of the skin is improved, fine wrinkles at the corners of the eyes are worrisome improvement, improvement of sagging under the eyes, improvement of lack of firmness and luster, improvement of lack of plumpness in the skin, improvement of easy makeup smudging, poor makeup application Improvement of poor skin condition, improvement of greasy face, improvement of acne proneness, improvement of itchy skin (skin itching) to do. These can be determined based on the results of skin condition questionnaires conducted by panelists who have been trained to be able to make objective evaluations, for example.

The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these.

[Test Example 1]
Thirty-three women aged 30 or older working at Fujicco Co., Ltd. were used as test subjects, and Test Example 1 was performed after a preliminary examination. The test subjects are adult women who do not have skin function diseases and do not have dry skin on a daily basis (the moisture content of the stratum corneum of the cheek is 60 or more). December).

<Preliminary inspection>
Subjects were asked to take 3 tablets (300 mg) of tablets containing Fujiflavone K25 (manufactured by Fujicco Co., Ltd., each 3 tablets containing 25 mg of isoflavones in terms of aglycone) per day for 2 days. was measured by high-performance liquid chromatography (Shimadzu Corporation, SPD-20A). If the equol concentration at this time is less than 1.0 [nmol/mg Cre], they are classified as "non-equol producers", and if the equol concentration is 1.0 [nmol/mg Cre] or more, they are classified as " equol producer”. There were 16 non-equol producers with an average equol concentration of 0.4 [nmol/mg Cre], and 16 equol producers with an average equol concentration of 11.4 [nmol/mg Cre]. rice field. Here, the unit [nmol/mg Cre] is a unit representing the amount per 1 mg of creatinine.

<Test Example 1>
Subjects were divided into a placebo group, a group taking isoflavones alone (hereinafter also referred to as a "single group"), and a group taking isoflavones and lactobionic acids so that the number of equol non-producers and equol producers were roughly the same. They were divided into 3 groups of a combined intake group (hereinafter also referred to as a "combined group"). Table 1 shows the number of subjects in the three groups.

A test edible tablet having the composition shown in Table 2 was prepared for each group, and 3 test edible tablets per day for each group were taken with water or lukewarm water, and this intake was continued for 12 weeks. Table 3 shows the daily intake of isoflavones (in terms of mass of isoflavone aglycones) and lactobionic acids (in terms of mass of lactobionic acid) derived from the test food tablets in each group.

The isoflavone concentration Cis [nmol/mg Cre] and the equol concentration Ceq [nmol/mg Cre] in the urine of the subjects were measured immediately before the start of intake of the test food tablet and on the day after 4 weeks had passed after the start of intake. Urinary isoflavone and equol concentrations were measured by high-performance liquid chromatography (Shimadzu Corporation, Prominence, LC-20 system). The isoflavone concentration is converted to isoflavone aglycone. Table 4 shows the average values measured by all subjects (total), Table 5 shows the average values measured by non-equol producers, and Table 6 shows the average values measured by equol producers.

In addition, the stratum corneum moisture content [a.u.] of the subject's cheeks was measured immediately before the start of intake of the test food tablets and on the next day after 4, 8, and 12 weeks had passed since the start of intake. The stratum corneum moisture content of the cheeks was measured at 5 points on the cheeks using a Corneomater CM825 (manufactured by Courage+Khazaka Electronic GmbH), and the average value was taken as the data for one time. The moisture content of the stratum corneum is obtained by indirectly calculating the moisture content of the stratum corneum using the dielectric constant of water and the capacitance that varies according to the moisture content of the stratum corneum. It has become. Table 7 shows the average values measured by all subjects (total), non-equol producers and equol producers. The moisture content of the stratum corneum of the cheek is expressed in arbitrary units (a.u.).

For all subjects (total), FIGS. 1 and 2 are bar graphs showing the results of Cis and Cis+Ceq shown in Table 4, and FIG. It is a diagram. For non-equol producers, FIGS. 4 and 5 are bar graphs showing the results of Cis and Cis+Ceq shown in Table 5, respectively, and FIG. is. For equol producers, FIGS. 7 and 8 are bar graphs showing the results of Cis and Cis+Ceq shown in Table 6, respectively, and FIG. be. "#" in FIGS. 1 to 9 indicates a significant difference between groups (p<0.05), and "##" indicates a significant difference between groups (p<0.01).

From the results shown in Table 4 and FIG. 1, for all subjects (total), in the combination group (combined intake of isoflavones and lactobionic acids), compared with the single group (single intake of isoflavones), isoflavones in urine It was confirmed that the average value of the concentration of was improved in the 4th week. From the results shown in Table 5 and FIG. 4, the combined intake of isoflavones and lactobionic acids in the non-equol non-producing subjects compared with the single group (ingestion of isoflavones alone) showed that the urinary isoflavones content was significantly higher. It was confirmed that the average value of the concentration was improved in the 4th week. From the results shown in Table 6 and FIG. 7, the concentration of isoflavones in the urine of the equol-producing subjects in the combination group (combined intake of isoflavones and lactobionic acids) was higher than that in the single group (intake of isoflavones alone). It was confirmed that the average value of was improved in the 4th week.

From the results shown in Table 7 and FIG. 3, for all subjects (total), in the combination group (combined intake of isoflavones and lactobionic acids), compared with the single group (single intake of isoflavones), It was confirmed that the moisture content of the stratum corneum was improved. From the results shown in Table 7 and FIG. 6, in the equol non-producers, the combination group (combined intake of isoflavones and lactobionic acids) was compared to the single group (single intake of isoflavones) at week 8 and week 12. It was confirmed that the stratum corneum moisture content of the eye cheeks was improved.

Isoflavones are known to have estrogenic activity, and it has been reported that estrogen activates skin fibroblasts when bound to estrogen receptors in the body, promoting the production of collagen and hyaluronic acid. there is Collagen and hyaluronic acid in the skin are major macromolecules involved in maintaining the structure of the skin, and are known to contribute to water retention in the skin. Therefore, it is considered that the increase in the concentration of isoflavones in urine in the combination group, that is, the promotion of absorption of isoflavones, contributed to the increase in the moisture content of the skin.

[Test Example 2]
Test Example 2 was conducted on 70 healthy adult females aged 30 or over who were concerned about dry skin as subjects after a preliminary examination.

<Preliminary inspection>
Subjects were asked to take 3 tablets (300 mg) of tablets containing Fujiflavone K25 (manufactured by Fujicco Co., Ltd., each 3 tablets containing 25 mg of isoflavones in terms of aglycone) per day for 2 days. was measured by high-performance liquid chromatography (Shimadzu Corporation, SPD-20A). If the equol concentration at this time is less than 1.0 [nmol/mg Cre], they are classified as "non-equol producers", and if the equol concentration is 1.0 [nmol/mg Cre] or more, they are classified as " equol producer”. There were 46 non-equol producers and 24 equol producers. Here, the unit [nmol/mg Cre] is a unit representing the amount per 1 mg of creatinine.

<Test Example 2>
The subjects were divided into 2 groups, 35 subjects in the placebo group and 35 subjects in the combined intake group of isoflavones and lactobionic acids (hereinafter also referred to as "combination group"), and a double-blind placebo-controlled parallel group comparison study was conducted. During the study period, one person in the placebo group withdrew from the study, and among the subjects after the completion of the study, those who took prohibited drugs and those who violated restrictions during the study period were excluded. Table 8 shows the final number of subjects in the two groups.

(i) Placebo group: Group taking placebo tablets (ii) Combination group: Soybean germ extract (powder) containing high-purity soybean-derived isoflavone glycosides daidzin, glycitin, and genistin (aglycone conversion 25 mg of lactobionic acid) and 250 mg of lactobionic acid in the combination group

All of the above tablets were tableted (300 mg/tablet) with a diameter of 9 mm. The tablets are based on maltodextrin, microcrystalline cellulose, micronized silicon dioxide, calcium stearate. In any group, one tablet was taken a day (after breakfast) with about a glass of water or lukewarm water for 12 weeks. For efficacy evaluation, the subjects visited the hospital every 4 weeks, and (a) measurement of isoflavone concentration in urine, (b) skin measurement, and (c) skin condition questionnaire were conducted. (b) Skin measurements included (b1) measurement of stratum corneum water content, (b2) measurement of transepidermal water loss (TEWL), and (b3) measurement of skin viscoelasticity.

(a) Measurement of Urinary Isoflavone Concentration The urinary isoflavone concentration Cis [nmol/mg Cre] of the subject was measured immediately before the start of intake of the test food tablet and on the day after 4, 8, and 12 weeks after the start of intake. did. The isoflavone concentration in urine was measured by high-performance liquid chromatography (Shimadzu Corporation, Prominence, LC-20 system). The isoflavone concentration is converted to isoflavone aglycone. Figures 10A, 10B, and 10C show the average urinary isoflavone concentrations Cis [nmol/mg Cre] in the subjects (Figure 10A: all subjects, Figure 10B: equol producers, Figure 10C: non-equol producers ).

(b) Skin measurement Skin measurement is performed after washing the measurement site, exposing the measurement site, and acclimating for 20 minutes or more in a constant temperature and humidity room at a temperature of 20 ± 5 ° C and a humidity of 50 ± 10%. was measured.

(b1) Measurement of stratum corneum moisture content The stratum corneum moisture content was measured by measuring the capacitance of the skin surface using a Corneometer (registered trademark) CM825 (Courage+Khazaka electronic GmbH). The larger the stratum corneum moisture content, the better. Figures 11A and 11B show the average values measured on the left cheek of the subjects (Figure 11A: all subjects; Figure 11B: non-equol producers), and Figures 12A and 12B show the average values measured on the left shin of the subjects. (Fig. 12A: all subjects; Fig. 12B: non-equol producers).

(b2) Measurement of transepidermal water loss (TEWL) Measurement of transepidermal water loss (TEWL) is performed using Tewameter (registered trademark) TM300 (Courage + Khazaka electronic GmbH), which is placed at the tip of the probe. This was done by measuring the temperature and humidity differences of moisture passing through two sets of highly sensitive temperature and humidity sensors. Figures 13A and 13B show the average values measured on the left cheek of the subjects (Figure 13A: all subjects; Figure 13B: non-equol producers), and Figures 14A and 14B show the average values measured on the left shin of the subjects. (Fig. 14A: all subjects; Fig. 14B: non-equol producers). A lower transepidermal water loss (TEWL) is better.

(b3) Measurement of skin viscoelasticity Skin viscoelasticity was measured for the left cheek using a Cutometer (registered trademark) MPA580 (Courage+Khazaka electronic GmbH, probe diameter 2 mm). Figures 15A and 15B show mean values of net elasticity (R5) (Figure 15A: all subjects; Figure 15B: non-equol producers), and Figures 16A and 16B show mean values of gross body elasticity (R2) ( FIG. 16A: all subjects; FIG. 16B: non-equol producers), FIG. 17A and FIG. FIG. 18B shows the mean values of unrecovered tonicity/retraction capacity (R1) (FIG. 18A: all subjects, FIG. 18B: non-equol producers). Of the measured values, net elasticity (R5), total body elasticity (R2), and return rate (R7) are values that decrease with aging, and the larger the value, the better. On the other hand, the unrecovered extensibility/retraction capacity (R1) is a value that increases with aging, and the smaller the value, the better.

(c) Skin Condition Questionnaire In the skin condition questionnaire, regarding skin symptoms in the last 4 weeks at the time of the questionnaire, the participants were concerned about pores, had rough texture, had rough skin, had spots and freckles, had a poor complexion, Skin lacks transparency, dull skin, dry skin, worrisome wrinkles around the corners of the eyes, sagging under the eyes, lack of firmness and luster, lack of plumpness, easy makeup loss, poor makeup application , Poor skin condition, oily face, pimple proneness, and itchy skin (skin itching), subjects answered their subjective symptoms. The subject was trained to objectively evaluate the skin condition questionnaire. As evaluation points, "1 point: I do not think so at all", "2 points: I do not think so much", "3 points: I cannot say either way", "4 points: I somewhat agree", and "5 points: I strongly agree". did. For any item, the smaller the score, the better. Figures 19A and 19B show the average scores of the subjects' assessment of puffiness under the eyes (Figure 19A: all subjects; Figure 19B: non-equol producers).

In the above figure, the following results were obtained in the efficacy analysis between the groups in the results. All the results of FIGS. 11A to 19B are the results when the value before ingestion is set to 0. In the figure, "#" indicates a significant difference between groups (P<0.05), "##" indicates a significant difference between groups (P<0.01), and "*" indicates before ingestion. "**" indicates a significant difference (P<0.01) from before ingestion.

<Results>
Regarding the moisture content of the stratum corneum (left cheek and left shin), the value of the combination group was higher than that of the placebo group throughout the intake. In particular, it was significantly larger at 4 weeks after ingestion (Fig. 11A, Fig. 12A).
Transepidermal water loss (TEWL) (left cheek) was lower in the combination group than in the placebo group at 4 and 8 weeks after ingestion. (left shin) was lower in the combination group than in the placebo group throughout the intake. Especially, it was significantly smaller at 4 weeks after ingestion (Fig. 14A).
Skin viscoelasticity (left cheek) net elasticity (R5), total body elasticity (R2), and rate of return (R7) were greater in the combination group than in the placebo group throughout ingestion. In particular, it was significantly greater at 8 weeks and 12 weeks after ingestion (Figs. 15A, 16A, and 17A). Regarding the unrecovered extensibility/retraction ability (R1) of skin viscoelasticity (left cheek), values were lower in the combination group than in the placebo group all the time after ingestion. Especially, it was significantly smaller at 8 weeks and 12 weeks after ingestion (Fig. 18A).
In the skin condition questionnaire, the combination group scored lower than the placebo group for "sagging under the eyes" throughout the period after intake. Especially, it was significantly smaller at 8 weeks and 12 weeks after ingestion (Fig. 19A). For the non-equol producers, almost the same tendency as the above-mentioned tendency for all subjects was confirmed (Figs. 12B, 13B, 14B, 15B, 16B, 17B, 18B, and 19B).

Isoflavones are known to have estrogenic activity, and it has been reported that estrogen activates skin fibroblasts when bound to estrogen receptors in the body, promoting the production of collagen and hyaluronic acid. there is Collagen and hyaluronic acid in the skin are major macromolecules involved in maintaining the structure of the skin, and are known to contribute to water retention in the skin. Therefore, in the combination group, the concentration of isoflavones in urine was improved (see FIGS. 10A, 10B, 10C, 1, 4, and 7), that is, the absorption of isoflavones was promoted. This is thought to have contributed to an increase in water volume, suppression of transepidermal water loss, improvement in skin viscoelasticity, improvement in skin condition, and suppression of sagging under the eyes.

Claims

An agent that is an isoflavone absorption enhancer and contains lactobionic acids.
A skin condition improving agent that contains lactobionic acids and has isoflavone absorption promoting action.
The agent according to claim 2, which is an agent for suppressing a decrease in skin moisture content, an agent for suppressing transepidermal water loss, or an agent for improving skin viscoelasticity.
The agent according to any one of claims 1 to 3, which is used for non-equol producers.
The agent according to any one of claims 1 to 4, further comprising isoflavones.
The agent according to claim 5, wherein the isoflavones are derived from soybeans.
The agent according to any one of claims 1 to 6, which is an oral agent.
The agent according to any one of claims 1 to 7, which is a food or drink composition.
　The use of lactobionic acids in the production of isoflavone absorption enhancers.