WO2022158595A1 - Promoteur d'absorption des isoflavones et inhibiteur de réduction de l'humidité de la peau - Google Patents

Promoteur d'absorption des isoflavones et inhibiteur de réduction de l'humidité de la peau Download PDF

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WO2022158595A1
WO2022158595A1 PCT/JP2022/002469 JP2022002469W WO2022158595A1 WO 2022158595 A1 WO2022158595 A1 WO 2022158595A1 JP 2022002469 W JP2022002469 W JP 2022002469W WO 2022158595 A1 WO2022158595 A1 WO 2022158595A1
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skin
isoflavones
isoflavone
equol
absorption
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PCT/JP2022/002469
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English (en)
Japanese (ja)
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彩加 川端
俊也 丸尾
利雄 鈴木
良太 赤木
裕一 卯川
健一 大江
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フジッコ株式会社
株式会社ダイセル
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Priority to JP2022537179A priority Critical patent/JP7166500B1/ja
Publication of WO2022158595A1 publication Critical patent/WO2022158595A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/30—Oestrogens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Definitions

  • 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.
  • isoflavones are not absorbed from the intestinal tract as glycosides, but can be hydrolyzed into aglycones by ⁇ -glycosidase produced by intestinal bacteria and absorbed in the intestinal tract.
  • Patent Document 1 lactic acid bacteria products containing polysaccharides
  • Patent Document 2 a culture of black koji mold
  • Patent Document 3 citrate or citric acid
  • 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.
  • 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.
  • the agent according to any one of [1] to [3] which is used for non-equol producers.
  • the present invention it is possible to provide a new agent that promotes absorption of isoflavones into the body.
  • 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.
  • FIG. 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 of all subjects (total) in Test Example 1.
  • FIG. 1 is a graph showing the total concentrations of isoflavones and equol of all subjects (to
  • 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. 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
  • 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. 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.
  • the isoflavone absorption enhancer of the present invention contains lactobionic acid.
  • An isoflavone absorption enhancer can promote absorption of isoflavones into the body of a subject by administering it to the subject.
  • 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.
  • 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.
  • the amount of estrogen secreted decreases after reaching the age of 40.
  • symptoms such as menopausal symptoms, forgetfulness and depression symptoms, dyslipidemia, breast atrophy, skin atrophy, and bone loss may occur.
  • An isoflavone absorption enhancer
  • 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.
  • equol which has strong estrogen-like activity and antioxidant activity
  • O-desmethylangolensin which has no activity.
  • the presence of equol-producing intestinal bacteria is essential for this metabolism.
  • equol 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • malonylated soybean isoflavone glycosides include malonylgenistin, malonyldaidzin, and malonylglycitin.
  • 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.
  • extracts 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.
  • 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 preparations of the present invention include, for example, animal drugs, quasi-drugs, pharmaceuticals, therapeutic drugs, prophylactic drugs, and the like.
  • the absorption of isoflavones can be promoted by administering the above-mentioned doses to the administration subject.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 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.
  • 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).
  • a display that is approved based on various systems established by the government and performed in a manner based on such approval.
  • 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.
  • 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.
  • the skin moisture reduction inhibitor of the present invention contains lactobionic acids.
  • 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.
  • 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).
  • transepidermal water loss inhibitor of the present invention contains lactobionic acid.
  • transepidermal water loss inhibitor contains lactobionic acid.
  • 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.
  • TEWL Transepidermal water loss
  • the skin viscoelasticity-improving agent of the present invention contains lactobionic acid.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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”.
  • 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.
  • 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.
  • 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).
  • the unit [nmol/mg Cre] is a unit representing the amount per 1 mg of creatinine.
  • 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
  • Table 6 shows the average values measured by equol producers.
  • 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.).
  • 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.
  • FIGS. 4 and 5 are bar graphs showing the results of Cis and Cis+Ceq shown in Table 5, respectively, and FIG. is.
  • 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).
  • 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.
  • 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 was conducted on 70 healthy adult females aged 30 or over who were concerned about dry skin as subjects after a preliminary examination.
  • the unit [nmol/mg Cre] is a unit representing the amount per 1 mg of creatinine.
  • 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.
  • Placebo group Group taking placebo tablets
  • 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.
  • one tablet was taken a day (after breakfast) with about a glass of water or lukewarm water for 12 weeks.
  • 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.
  • Skin measurements included (b1) measurement of stratum corneum water content, (b2) measurement of transepidermal water loss (TEWL), and (b3) measurement of skin viscoelasticity.
  • 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 ).
  • (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).
  • TEWL transepidermal water loss
  • Tewameter registered trademark
  • TM300 Cosmetic + Khazaka electronic GmbH
  • 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.
  • net elasticity R5
  • total body elasticity R2
  • return rate R7
  • unrecovered extensibility/retraction capacity R1
  • 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).
  • 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.
  • 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.

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Abstract

La présente invention a pour objet de réaliser un nouvel agent pour favoriser l'absorption des isoflavones dans le corps. La présente invention concerne un promoteur d'absorption des isoflavones, le promoteur d'absorption des isoflavones étant un agent qui contient un acide lactobionique.
PCT/JP2022/002469 2021-01-25 2022-01-24 Promoteur d'absorption des isoflavones et inhibiteur de réduction de l'humidité de la peau WO2022158595A1 (fr)

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JP2004024139A (ja) * 2002-06-26 2004-01-29 Mitsukan Group Honsha:Kk 健康食品素材
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JP2008001608A (ja) * 2006-06-20 2008-01-10 Unitika Ltd エコール産生促進組成物
JP2008278776A (ja) * 2007-05-09 2008-11-20 Unitika Ltd ラクトビオン酸含有発酵乳の製造方法
JP2010037258A (ja) * 2008-08-04 2010-02-18 Toyo Suisan Kaisha Ltd ポリフェノールの吸収促進剤
JP2011153090A (ja) * 2010-01-27 2011-08-11 Unitika Ltd 皮膚老化防止・改善剤
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JP2004024139A (ja) * 2002-06-26 2004-01-29 Mitsukan Group Honsha:Kk 健康食品素材
JP2007119429A (ja) * 2005-10-31 2007-05-17 Ichimaru Pharcos Co Ltd ペルオキシソーム増殖剤応答性受容体活性化剤
JP2008001608A (ja) * 2006-06-20 2008-01-10 Unitika Ltd エコール産生促進組成物
JP2008278776A (ja) * 2007-05-09 2008-11-20 Unitika Ltd ラクトビオン酸含有発酵乳の製造方法
JP2010037258A (ja) * 2008-08-04 2010-02-18 Toyo Suisan Kaisha Ltd ポリフェノールの吸収促進剤
JP2011153090A (ja) * 2010-01-27 2011-08-11 Unitika Ltd 皮膚老化防止・改善剤
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