WO2012165610A1 - Composition for maintaining or improving skin barrier function - Google Patents

Composition for maintaining or improving skin barrier function Download PDF

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Publication number
WO2012165610A1
WO2012165610A1 PCT/JP2012/064259 JP2012064259W WO2012165610A1 WO 2012165610 A1 WO2012165610 A1 WO 2012165610A1 JP 2012064259 W JP2012064259 W JP 2012064259W WO 2012165610 A1 WO2012165610 A1 WO 2012165610A1
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Prior art keywords
barrier function
taurine
skin barrier
skin
aging
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PCT/JP2012/064259
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French (fr)
Japanese (ja)
Inventor
憲一 高野
拓人 武井
友紀 井野口
周子 武藤
知佳 真邉
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大正製薬株式会社
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Priority to JP2013518184A priority Critical patent/JP6238406B2/en
Publication of WO2012165610A1 publication Critical patent/WO2012165610A1/en

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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • 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
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to an oral composition having an action of maintaining a skin barrier function in normal skin and restoring the skin barrier function in broken skin. More specifically, taurine is used as an active ingredient, mainly suppressing the decrease in skin barrier function due to aging, restoring the reduced skin barrier function to a normal level, and functioning when the skin barrier function is destroyed. It is related with the composition for oral use which has the effect
  • Such a skin state is sometimes referred to as “a state in which the skin barrier function is lowered”.
  • the skin barrier function refers to the ability of the stratum corneum to retain moisture. If this decreases, the skin surface tends to dry out, causing problems such as various bacteria, allergens, and irritating factors. Sometimes.
  • This skin barrier function is evaluated using the skin stratum corneum water content and transepidermal water transpiration (TEWL) as an index (see Non-Patent Document 1), but atopy is a typical disease that causes abnormal skin barrier function. In patients with atopic dermatitis, there is a report that the stratum corneum moisture content is about one-fifth and the transdermal moisture transpiration amount is about four times that of healthy individuals (see Non-Patent Document 2).
  • Non-Patent Document 3 In order to evaluate the state of wrinkles, there are known models that induce wrinkles by continuously irradiating mice with ultraviolet rays, and models that induce wrinkles by feeding mice with special diets that are deficient in minerals and fatty acids (non-wrinkle). (See Patent Documents 4 and 5).
  • NMF Natural Moisturizing Factor
  • Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid with a simple chemical structure with a molecular weight of 125.15. Unlike amino acids that make up proteins, it acts like vitamins and hormones, as well as cranial nerves. It is known to exhibit various pharmacological actions including system, circulatory system, and hepatobiliary system (see Non-Patent Document 6). As described above, taurine has been attracting attention as a physiologically active substance and has been widely used. However, there is no report that it is incorporated into an oral composition and provided as an agent for maintaining or improving the skin barrier function.
  • Non-Patent Document 7 it is known that wrinkles occur when the elasticity of the skin tissue decreases due to natural aging due to aging and photoaging due to ultraviolet rays or the like.
  • the present invention has an action of preventing or improving wrinkles caused by aging while suppressing a decrease in skin barrier function caused by aging, or promoting repair of skin barrier function destroyed due to aging.
  • An object of the present invention is to provide a new type of oral composition.
  • the inventors of the present invention have found that the amount of taurine in the skin decreases with aging through examination of how factors involved in skin components change due to aging.
  • taurine was orally administered to mice with reduced skin barrier function, and the skin barrier function of the mouse was evaluated by measuring the skin stratum corneum water content and transepidermal water transpiration (TEWL).
  • TEWL transepidermal water transpiration
  • the inventors have found that it has the action of suppressing the generation of wrinkles due to aging or improving the generated wrinkles.
  • an oral composition that has an action of preventing or improving wrinkles caused by aging while suppressing a decrease in skin barrier function due to aging or promoting repair of a broken skin barrier function. It became possible to provide.
  • the present invention relates to an oral composition for maintaining or improving the skin barrier function, characterized by containing taurine as an active ingredient.
  • skin barrier function means the ability of the stratum corneum of skin to retain moisture. The state of skin barrier function is judged using keratin water content and transepidermal water transpiration as indicators, and when the skin barrier function decreases, keratin water content decreases and transepidermal water transpiration increases, while skin barrier function When improved, the amount of stratum corneum increases and the amount of transepidermal water transpiration decreases.
  • the oral composition of the present invention is particularly effective for suppressing or improving a decrease in skin barrier function due to aging.
  • aging as used herein includes natural aging caused by aging and photoaging caused by ultraviolet rays and the like, but the oral composition of the present invention can be applied to any reduction in skin barrier function due to aging. is there.
  • the oral composition of the present invention is effective in preventing and improving skin wrinkles, particularly wrinkles caused by aging.
  • the oral composition of the present invention can be in the form of a pharmaceutical composition or a food or drink. Since the oral composition of the present invention has an action of maintaining or improving the skin barrier function, it is administered orally for the prevention or improvement (treatment) of symptoms and diseases caused by the reduction of the skin barrier function, such as wrinkles. It can be suitably used as a pharmaceutical composition to be used or as a food or drink that is taken daily for maintaining or improving the skin barrier function.
  • the oral composition of the present invention can be provided by a conventional method, for example, as a solid preparation for internal use such as a powder, granule, tablet, or a liquid preparation such as a drink.
  • a pharmaceutical carrier suitable for each form is used, but there is no particular limitation as long as it is suitable for oral administration.
  • the oral composition of the present invention When used as a pharmaceutical composition, one or more other components effective for maintaining or improving the skin barrier function can be blended. Moreover, you may use together with the other pharmaceutical composition effective in maintenance or improvement of a skin barrier function.
  • the oral composition of the present invention when used as a food or drink, can be, for example, a health food, a functional food, a food for specified health use, a nutritional supplement, a food for the sick, or a food additive. .
  • food and drink include liquid products such as drinks, soups, milk drinks, soft drinks, tea drinks, alcoholic drinks, jelly-like drinks, functional drinks; oils such as edible oils, dressings, mayonnaise, margarines Products containing carbohydrates; Foods containing carbohydrates such as rice, noodles and bread; Livestock processed foods such as ham and sausage; Fish processed foods such as kamaboko, dried fish and salted; Vegetable processed foods such as pickles; Semis such as jelly and yogurt Solid foods; Fermented foods such as miso and fermented beverages; Various confectionery such as Western confectionery, Japanese confectionery, candy, gums, gummi, frozen confectionery, ice confectionery; Retort products such as curry, sauce, Chinese soup; Examples include instant foods such as instant miso soup and foods for microwave ovens. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included.
  • Manufacture of food and drink can be carried out by manufacturing techniques known in the technical field.
  • the preferred form of the oral composition of the present invention is an aqueous beverage (for example, an internal liquid such as a drink or a liquid product such as a drink).
  • An aqueous beverage in a container such as a bottle having a pH adjusted to 2.5 to 7.0, preferably 4.5 to 6.5.
  • An appropriate pH adjuster can be used for adjusting the pH in consideration of the ingestibility and the like. Examples of such pH adjusters include citric acid, malic acid, fumaric acid, adipic acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, or salts thereof.
  • Water-based beverages prepared in this way are provided by filling them into molded containers (so-called PET bottles) based on polyethylene terephthalate, metal cans, paper containers combined with metal foil and plastic films, glass bottles, etc. Is done.
  • the content (formulation) of “taurine” is 0.1 to 10% by mass in the oral composition, preferably 0.5 to 5% by mass, more preferably 1 to 3% by mass. If it is 0.1% by mass or less, it is not preferable from the viewpoint of maintaining and improving the skin barrier function, and if it exceeds 10% by mass, it is not preferable from the viewpoint of solubility of taurine when it is in the form of a beverage.
  • the present invention also provides a method for maintaining or improving the skin barrier function in a subject, characterized by administering or ingesting the oral composition of the present invention to the subject. Moreover, the method for suppressing or improving the fall of the skin barrier function by the aging in a subject characterized by administering the composition for oral administration of this invention to a subject is also provided. Furthermore, the present invention also provides a method for preventing or improving wrinkles due to aging in a subject, which comprises administering the oral composition of the present invention to the subject.
  • the product of the oral composition of the present invention may be labeled with an indication that it is used to maintain or improve the skin barrier function.
  • labeled product or instructions means that the product body, container, packaging, etc. are marked, or instructions, package inserts, promotional materials, or other printed materials that disclose product information. It means that the display is attached to.
  • the indication to be used to maintain or improve the skin barrier function may include information on the mechanism by which the skin barrier function is maintained or improved by administering or ingesting the oral composition of the present invention. it can. Moreover, the information regarding the symptom resulting from the fall of a skin barrier function, or being used for the prevention or improvement of a disease can be included.
  • Test Example 2 Change of Taurine Content in the Skin by Oral Administration of Taurine Using 5-week-old HR-1 female mice (purchased from Japan SLC Co., Ltd.), 10 mice per group, reared up to 32 weeks of age, A 3% aqueous solution of taurine was administered for 4 weeks. On the other hand, purified water was administered to the control group. After administration, skin was collected in the same manner as in Test Example 1, and the amount of taurine in the skin was measured.
  • Test Example 3 Effect of Taurine Administration on Skin Function Decreased by Ultraviolet Irradiation Using 7-week-old HR-1 male mice (purchased from Japan SLC Co., Ltd.), 10 mice per group, and ultraviolet rays (irradiation on the back of the mice) A dose of 70-100 mJ / cm 2 ) was irradiated 3 times a week for 4 weeks. Meanwhile, 3% aqueous taurine solution was administered as a mixed water. On the other hand, purified water was administered to the control group. After the final administration, the horny layer moisture content and transdermal moisture transpiration of the back skin were measured.
  • Test Example 4 Effect of Taurine Administration Before Wrinkle Generation on Wrinkles Generated by Ultraviolet Irradiation Using 8 week old HR-1 male mice (purchased from Japan SLC Co., Ltd.), 9 to 10 animals per group The back of the mouse was irradiated with ultraviolet rays (irradiation amount 70-100 mJ / cm 2 ) three times a week for 8 weeks. Meanwhile, 3% aqueous taurine solution was administered as a mixed water. On the other hand, purified water was administered to the control group. After the final administration, wrinkles on the back skin were evaluated according to the above criteria and scored.
  • Test Example 5 Effect of Taurine Administration on Wrinkles Generated by Ultraviolet Irradiation Using 7-week-old HR-1 male mice (purchased from Japan SLC Co., Ltd.), 10 mice per group, and ultraviolet rays (irradiation dose on the back of mice) (70-100 mJ / cm 2 ) was irradiated 3 times a week for 12 weeks. From 8 weeks after the start of ultraviolet irradiation (after the occurrence of significant wrinkles was confirmed), a 3% taurine aqueous solution was administered as a mixed water for 4 weeks. On the other hand, purified water was administered to the control group. After the final administration, wrinkles on the back skin were evaluated according to the above criteria and scored.
  • an oral composition having an action of suppressing deterioration of skin barrier function or promoting repair of destroyed skin barrier function and preventing or improving wrinkles caused by aging is used, for example. It is expected to contribute to the development of the anti-aging industry and the like by providing it in the form of an aqueous beverage such as liquids and drinks.

Abstract

An oral composition for maintaining or improving a skin barrier function, characterized by containing taurine as an active ingredient; or an oral composition for preventing or ameliorating age-related wrinkling, characterized by containing taurine as an active ingredient.

Description

皮膚バリア機能の維持又は改善のための組成物Composition for maintaining or improving skin barrier function
　本発明は、正常な皮膚においては皮膚バリア機能を維持し、破壊された皮膚においては皮膚バリア機能を修復する作用を有する経口用組成物に関する。より詳しくは、タウリンを有効成分とし、主に老化に伴う皮膚バリア機能の低下を抑制し、低下した皮膚バリア機能を正常なレベルに回復させるとともに、皮膚バリア機能が破壊された場合にはその機能を修復する作用を有する経口用組成物に関する。 The present invention relates to an oral composition having an action of maintaining a skin barrier function in normal skin and restoring the skin barrier function in broken skin. More specifically, taurine is used as an active ingredient, mainly suppressing the decrease in skin barrier function due to aging, restoring the reduced skin barrier function to a normal level, and functioning when the skin barrier function is destroyed. It is related with the composition for oral use which has the effect | action which repairs.
　皮膚の柔軟性及びその機能は、角質層の含水分の影響を受けることが知られている。老化した皮膚では、表皮、真皮ともに細胞数が減少し、代謝機能が低下し、その結果、角質層の水分保持機能が低下して、皮膚が菲薄化した状態になり、柔軟性及び弾力性を失って、荒れ肌様の状態になるものと考えられている。 It is known that the flexibility and function of the skin are affected by the moisture content of the stratum corneum. In aging skin, the number of cells in both the epidermis and dermis is reduced and the metabolic function is lowered.As a result, the water retention function of the stratum corneum is lowered, the skin becomes thinned, and the flexibility and elasticity are reduced. It is thought to be lost and become a rough skin.
　このような皮膚の状態を指称して「皮膚バリア機能が低下した状態」と言うことがある。皮膚バリア機能とは、角質層が水分を保持する能力のことであり、これが低下すると、皮膚表面が乾燥し易くなって、種々の細菌、アレルゲン、刺激因子などが侵入しやすくなるという問題を生じることがある。この皮膚バリア機能は、皮膚の角質層水分量や経表皮水分蒸散量（TEWL）を指標として評価されるが（非特許文献１参照）、皮膚バリア機能が異常をきたす典型的な疾患であるアトピー性皮膚炎患者において、各指標を健常人と比較すると、角質層水分量について約５分の１、経皮水分蒸散量について約４倍になるとの報告がある（非特許文献２参照）。 Such a skin state is sometimes referred to as “a state in which the skin barrier function is lowered”. The skin barrier function refers to the ability of the stratum corneum to retain moisture. If this decreases, the skin surface tends to dry out, causing problems such as various bacteria, allergens, and irritating factors. Sometimes. This skin barrier function is evaluated using the skin stratum corneum water content and transepidermal water transpiration (TEWL) as an index (see Non-Patent Document 1), but atopy is a typical disease that causes abnormal skin barrier function. In patients with atopic dermatitis, there is a report that the stratum corneum moisture content is about one-fifth and the transdermal moisture transpiration amount is about four times that of healthy individuals (see Non-Patent Document 2).
　また、皮膚バリア機能が低下すると、シワが発生することが知られている（非特許文献３参照）。シワの状態を評価するために、マウスに紫外線を連続照射しシワを誘発するモデルや、ミネラルや脂肪酸を欠乏させた特殊飼料をマウスに給餌してシワを誘発するモデルが知られている（非特許文献４及び５参照）。 Further, it is known that wrinkles occur when the skin barrier function is lowered (see Non-Patent Document 3). In order to evaluate the state of wrinkles, there are known models that induce wrinkles by continuously irradiating mice with ultraviolet rays, and models that induce wrinkles by feeding mice with special diets that are deficient in minerals and fatty acids (non-wrinkle). (See Patent Documents 4 and 5).
　そして、このような老化した皮膚の改善剤としては、ＮＭＦ(Natural　Moisturizing　Factor)と呼称される成分、あるいは、コラーゲン、ヒアルロン酸といった成分を配合した化粧料、外用剤が数多く提供されているが、皮膚バリア機能の維持や改善に極めて有効な組成物は未だ提供されていないというのが実状である。 And as such an aging skin improving agent, there are many cosmetics and external preparations that contain components called NMF (Natural Moisturizing Factor), or components such as collagen and hyaluronic acid. The fact is that a composition that is extremely effective for maintaining or improving the skin barrier function has not yet been provided.
　一方、タウリン（２－アミノエタンスルホン酸）は、分子量１２５．１５の単純な化学構造をもつ含硫アミノ酸で、タンパク質を構成するアミノ酸とは異なり、ビタミン類やホルモンのような作用、さらには脳神経系、循環系、肝胆系をはじめとした様々な薬理作用を示すことが知られている（非特許文献６参照）。このように生理活性物質として注目され、広汎に利用されてきたタウリンであるが、これを経口用組成物に配合し、皮膚バリア機能の維持・改善剤として提供されたという報告はない。 Taurine (2-aminoethanesulfonic acid), on the other hand, is a sulfur-containing amino acid with a simple chemical structure with a molecular weight of 125.15. Unlike amino acids that make up proteins, it acts like vitamins and hormones, as well as cranial nerves. It is known to exhibit various pharmacological actions including system, circulatory system, and hepatobiliary system (see Non-Patent Document 6). As described above, taurine has been attracting attention as a physiologically active substance and has been widely used. However, there is no report that it is incorporated into an oral composition and provided as an agent for maintaining or improving the skin barrier function.
　なお、シワは、加齢による自然老化と紫外線等による光老化により、皮膚組織の弾力性が低下することによって起こることが知られている（非特許文献７参照）。 In addition, it is known that wrinkles occur when the elasticity of the skin tissue decreases due to natural aging due to aging and photoaging due to ultraviolet rays or the like (see Non-Patent Document 7).
　本発明は、老化に基因する皮膚バリア機能の低下を抑制し、又は、老化に基因して破壊された皮膚バリア機能の修復を促進するとともに、老化に基因するシワを予防又は改善する作用を有する、新しいタイプの経口用組成物を提供することを課題とする。 The present invention has an action of preventing or improving wrinkles caused by aging while suppressing a decrease in skin barrier function caused by aging, or promoting repair of skin barrier function destroyed due to aging. An object of the present invention is to provide a new type of oral composition.
　本発明者らは、皮膚の構成成分に関与する因子が老化によってどのように変化するかの検討を通じて、老化とともに皮膚中のタウリン量が減少するということを見出した。 The inventors of the present invention have found that the amount of taurine in the skin decreases with aging through examination of how factors involved in skin components change due to aging.
　そこで、皮膚バリア機能が低下したマウスにタウリンを経口投与し、皮膚の角層水分量や経表皮水分蒸散量（TEWL）の測定によって当該マウスの皮膚バリア機能を評価したところ、タウリンの作用により、皮膚バリア機能の低下が抑制されたり、皮膚バリア機能が向上したり、破壊された皮膚バリア機能が修復されるという知見を得た。 Therefore, taurine was orally administered to mice with reduced skin barrier function, and the skin barrier function of the mouse was evaluated by measuring the skin stratum corneum water content and transepidermal water transpiration (TEWL). The present inventors have found that the decrease in skin barrier function is suppressed, the skin barrier function is improved, and the destroyed skin barrier function is repaired.
　また、老化に基因するシワの生成を抑制し、又は、生成したシワを改善する作用も有するとの知見を得た。 In addition, the inventors have found that it has the action of suppressing the generation of wrinkles due to aging or improving the generated wrinkles.
　かかる知見より得られた本発明の態様は、次のとおりである。
（１）タウリンを有効成分として含有することを特徴とする、皮膚バリア機能を維持又は改善するための経口用組成物。
（２）タウリンを有効成分として含有することを特徴とする、老化による皮膚バリア機能の低下を抑制又は改善するための経口用組成物。
（３）タウリンを有効成分として含有することを特徴とする、老化によるシワを予防又は改善するための経口用組成物。
（４）水性飲料である前記（１）～（３）に記載の経口用組成物。
（５）ｐＨが２．５～７．０である前記（４）に記載の経口用組成物。 The aspects of the present invention obtained from such findings are as follows.
(1) An oral composition for maintaining or improving the skin barrier function, comprising taurine as an active ingredient.
(2) An oral composition for suppressing or improving a decrease in skin barrier function due to aging, comprising taurine as an active ingredient.
(3) An oral composition for preventing or improving wrinkles due to aging, comprising taurine as an active ingredient.
(4) The oral composition according to (1) to (3), which is an aqueous beverage.
(5) The oral composition according to (4), wherein the pH is 2.5 to 7.0.
　本発明により、老化に伴う皮膚バリア機能の低下を抑制し、又は、破壊された皮膚バリア機能の修復を促進するとともに、老化に基因するシワを予防又は改善する作用を有する、経口用組成物を提供することが可能となった。 According to the present invention, there is provided an oral composition that has an action of preventing or improving wrinkles caused by aging while suppressing a decrease in skin barrier function due to aging or promoting repair of a broken skin barrier function. It became possible to provide.
マウスの表皮におけるタウリン量の老化による変化を示すグラフである。「**」は１２週齢時の値に対して、ｐ＜０．０１であることを示す。It is a graph which shows the change by the aging of the amount of taurine in the epidermis of a mouse | mouth. “**” indicates that p <0.01 with respect to the value at the age of 12 weeks. マウスの真皮におけるタウリン量の老化による変化を示すグラフである。「**」は１２週齢時の値に対して、ｐ＜０．０１であることを示す。It is a graph which shows the change by aging of the amount of taurine in the dermis of a mouse. “**” indicates that p <0.01 with respect to the value at the age of 12 weeks. タウリンを経口投与した際の、表皮におけるタウリン量の変化を示すグラフである。「**」は溶媒投与群の値に対して、ｐ＜０．０１であることを示す。It is a graph which shows the change of the amount of taurine in an epidermis when taurine is orally administered. “**” indicates that p <0.01 with respect to the value of the solvent administration group. タウリンを経口投与した際の、真皮におけるタウリン量の変化を示すグラフである。It is a graph which shows the change of the amount of taurines in the dermis when taurine is orally administered. タウリンを経口投与した際の、紫外線照射により低下した角層水分量の変化を示すグラフである。群間比較において「*」はｐ＜０．０５、「**」はｐ＜０．０１であることを示す。It is a graph which shows the change of the stratum corneum moisture content which decreased by the ultraviolet irradiation at the time of orally administering taurine. In the comparison between groups, “*” indicates p <0.05, and “**” indicates p <0.01. タウリンを経口投与した際の、紫外線照射により増加した経皮水分蒸散量の変化を示すグラフである。群間比較において「**」はｐ＜０．０１であることを示す。It is a graph which shows the change of the transdermal moisture transpiration | evaporation amount increased by ultraviolet irradiation at the time of administering taurine orally. In the comparison between groups, “**” indicates p <0.01. タウリンを経口投与した際の、紫外線照射により発生したシワの変化を示すグラフである。群間比較において「**」はｐ＜０．０１であることを示す。It is a graph which shows the change of the wrinkle which generate | occur | produced by the ultraviolet irradiation at the time of administering taurine orally. In the comparison between groups, “**” indicates p <0.01. 紫外線照射によりシワを発生させた後、タウリンを経口投与した際のシワの変化を示すグラフである。群間比較において「**」はｐ＜０．０１であることを示す。It is a graph which shows the change of a wrinkle at the time of orally administering taurine after generating wrinkles by ultraviolet irradiation. In the comparison between groups, “**” indicates p <0.01.
　本発明は、タウリンを有効成分として含有することを特徴とする、皮膚バリア機能を維持又は改善するための経口用組成物に関する。 The present invention relates to an oral composition for maintaining or improving the skin barrier function, characterized by containing taurine as an active ingredient.
　本発明において「皮膚バリア機能」とは、皮膚の角質層が水分を保持する能力を意味する。皮膚バリア機能の状態は、角質水分量と経表皮水分蒸散量を指標として判断され、皮膚バリア機能が低下すると角質水分量が減少し、経表皮水分蒸散量が増加し、一方、皮膚バリア機能が改善されると角質水分量が増加し、経表皮水分蒸散量が減少するという関係にある。 In the present invention, “skin barrier function” means the ability of the stratum corneum of skin to retain moisture. The state of skin barrier function is judged using keratin water content and transepidermal water transpiration as indicators, and when the skin barrier function decreases, keratin water content decreases and transepidermal water transpiration increases, while skin barrier function When improved, the amount of stratum corneum increases and the amount of transepidermal water transpiration decreases.
　本発明の経口用組成物は、特に、老化による皮膚バリア機能の低下を抑制又は改善するために有効である。ここで言う「老化」には、加齢により生じる自然老化と紫外線等により生じる光老化が含まれるが、本発明の経口用組成物は、いずれの老化による皮膚バリア機能の低下にも適用可能である。 The oral composition of the present invention is particularly effective for suppressing or improving a decrease in skin barrier function due to aging. The term “aging” as used herein includes natural aging caused by aging and photoaging caused by ultraviolet rays and the like, but the oral composition of the present invention can be applied to any reduction in skin barrier function due to aging. is there.
　本発明の経口用組成物は、皮膚のシワ、特に老化に基因するシワの予防や改善に有効である。 The oral composition of the present invention is effective in preventing and improving skin wrinkles, particularly wrinkles caused by aging.
　本発明の経口用組成物は、医薬組成物あるいは飲食品の形態であり得る。本発明の経口用組成物は、皮膚バリア機能を維持又は改善させる作用を有するため、皮膚バリア機能の低下に起因する症状や病気、例えば、シワなどの予防又は改善（治療）のために経口投与される医薬組成物として、また、皮膚バリア機能を維持又は改善するために日常的に摂取される飲食品として好適に用いることができる。 The oral composition of the present invention can be in the form of a pharmaceutical composition or a food or drink. Since the oral composition of the present invention has an action of maintaining or improving the skin barrier function, it is administered orally for the prevention or improvement (treatment) of symptoms and diseases caused by the reduction of the skin barrier function, such as wrinkles. It can be suitably used as a pharmaceutical composition to be used or as a food or drink that is taken daily for maintaining or improving the skin barrier function.
　本発明の経口用組成物は、常法により、例えば、散剤、顆粒剤、錠剤等の内服用固形剤やドリンク剤などの内服液剤として提供することができる。この際、それぞれの形態に相応しい製剤用キャリアが使用されるが、経口投与に適するものであれば特に限定はない。 The oral composition of the present invention can be provided by a conventional method, for example, as a solid preparation for internal use such as a powder, granule, tablet, or a liquid preparation such as a drink. At this time, a pharmaceutical carrier suitable for each form is used, but there is no particular limitation as long as it is suitable for oral administration.
　本発明の経口用組成物を医薬組成物として用いる場合には、皮膚バリア機能の維持又は改善に有効な１種もしくは２種以上の他の成分を配合することができる。また、皮膚バリア機能の維持又は改善に有効な他の医薬組成物と併用してもよい。 When the oral composition of the present invention is used as a pharmaceutical composition, one or more other components effective for maintaining or improving the skin barrier function can be blended. Moreover, you may use together with the other pharmaceutical composition effective in maintenance or improvement of a skin barrier function.
　本発明の経口用組成物を飲食品として用いる場合、当該飲食品は、例えば、健康食品、機能性食品、特定保健用食品、栄養補助食品、病者用食品、あるいは食品添加物、であり得る。飲食品の具体例としては、ドリンク類、スープ類、乳飲料、清涼飲料水、茶飲料、アルコール飲料、ゼリー状飲料、機能性飲料等の液状製品；食用油、ドレッシング、マヨネーズ、マーガリンなどの油分を含む製品；飯類、麺類、パン類等の炭水化物含有食品；ハム、ソーセージ等の畜産加工食品；かまぼこ、干物、塩辛等の水産加工食品；漬物等の野菜加工食品；ゼリー、ヨーグルト等の半固形状食品；みそ、発酵飲料等の発酵食品；洋菓子類、和菓子類、キャンディー類、ガム類、グミ、冷菓、氷菓等の各種菓子類；カレー、あんかけ、中華スープ等のレトルト製品；インスタントスープ，インスタントみそ汁等のインスタント食品や電子レンジ対応食品等が挙げられる。さらには、粉末、穎粒、錠剤、カプセル剤、液状、ペースト状またはゼリー状に調製された健康飲食品も挙げられる。 When the oral composition of the present invention is used as a food or drink, the food or drink can be, for example, a health food, a functional food, a food for specified health use, a nutritional supplement, a food for the sick, or a food additive. . Specific examples of food and drink include liquid products such as drinks, soups, milk drinks, soft drinks, tea drinks, alcoholic drinks, jelly-like drinks, functional drinks; oils such as edible oils, dressings, mayonnaise, margarines Products containing carbohydrates; Foods containing carbohydrates such as rice, noodles and bread; Livestock processed foods such as ham and sausage; Fish processed foods such as kamaboko, dried fish and salted; Vegetable processed foods such as pickles; Semis such as jelly and yogurt Solid foods; Fermented foods such as miso and fermented beverages; Various confectionery such as Western confectionery, Japanese confectionery, candy, gums, gummi, frozen confectionery, ice confectionery; Retort products such as curry, sauce, Chinese soup; Examples include instant foods such as instant miso soup and foods for microwave ovens. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included.
　飲食品の製造は、当該技術分野に公知の製造技術により実施することができる。当該飲食品においては、皮膚バリア機能の維持又は改善に有効な１種もしくは２種以上の成分を配合してもよい。また、皮膚バリア機能の維持又は改善以外の機能を発揮する他の成分あるいは他の機能性食品と組み合わせることによって、多機能性の飲食品としてもよい。 Manufacture of food and drink can be carried out by manufacturing techniques known in the technical field. In the said food-drinks, you may mix | blend 1 type, or 2 or more types of components effective in maintenance or improvement of a skin barrier function. Moreover, it is good also as multifunctional food-drinks by combining with the other component which exhibits functions other than maintenance or improvement of a skin barrier function, or another functional food.
　タウリンは水溶液中で比較的安定な化合物であることから、本発明の経口用組成物の好適な形態は水性飲料（例えば、ドリンク剤等の内服液剤やドリンク類等の液状製品）であり、特にｐＨが２．５～７．０、好ましくは４．５～６．５に調整された瓶等の容器入りの水性飲料である。服用性等を考慮したｐＨの調整には、適当なｐＨ調整剤を使用することができる。このようなｐＨ調整剤としては、クエン酸、リンゴ酸、フマル酸、アジピン酸、グルコン酸、酒石酸、アスコルビン酸、酢酸、リン酸又はそれらの塩が挙げられる。 Since taurine is a relatively stable compound in an aqueous solution, the preferred form of the oral composition of the present invention is an aqueous beverage (for example, an internal liquid such as a drink or a liquid product such as a drink). An aqueous beverage in a container such as a bottle having a pH adjusted to 2.5 to 7.0, preferably 4.5 to 6.5. An appropriate pH adjuster can be used for adjusting the pH in consideration of the ingestibility and the like. Examples of such pH adjusters include citric acid, malic acid, fumaric acid, adipic acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, or salts thereof.
　こうして調製された「水性飲料」は、ポリエチレンテレフタレートを主成分とする成形容器（いわゆるＰＥＴボトル）、金属缶、金属箔やプラスチックフィルムと複合された紙容器、ガラス製の瓶などに充填して提供される。 “Water-based beverages” prepared in this way are provided by filling them into molded containers (so-called PET bottles) based on polyethylene terephthalate, metal cans, paper containers combined with metal foil and plastic films, glass bottles, etc. Is done.
　「タウリン」の含有（配合）量は、経口用組成物中０.１～１０質量％であり、好ましくは０.５～５質量％、より好ましくは１～３質量％である。０．１質量％以下では皮膚バリア機能の維持・改善の点から好ましくなく、１０質量％を超えると飲料の形態とした場合、タウリンの溶解性の点から好ましくないからである。 The content (formulation) of “taurine” is 0.1 to 10% by mass in the oral composition, preferably 0.5 to 5% by mass, more preferably 1 to 3% by mass. If it is 0.1% by mass or less, it is not preferable from the viewpoint of maintaining and improving the skin barrier function, and if it exceeds 10% by mass, it is not preferable from the viewpoint of solubility of taurine when it is in the form of a beverage.
　本発明は、このように、本発明の経口用組成物を対象に投与もしくは摂取させることを特徴とする、対象における皮膚バリア機能を維持又は改善する方法をも提供するものである。また、本発明の経口用組成物を対象に投与することを特徴とする、対象における老化による皮膚バリア機能の低下を抑制又は改善する方法をも提供するものである。さらに、本発明の経口用組成物を対象に投与することを特徴とする、対象における老化によるシワを予防又は改善する方法をも提供するものである。 Thus, the present invention also provides a method for maintaining or improving the skin barrier function in a subject, characterized by administering or ingesting the oral composition of the present invention to the subject. Moreover, the method for suppressing or improving the fall of the skin barrier function by the aging in a subject characterized by administering the composition for oral administration of this invention to a subject is also provided. Furthermore, the present invention also provides a method for preventing or improving wrinkles due to aging in a subject, which comprises administering the oral composition of the present invention to the subject.
　本発明の経口用組成物の製品（医薬品、飲食品）またはその説明書は、皮膚バリア機能を維持又は改善させるために用いられる旨の表示を付したものであり得る。ここで「製品または説明書に表示を付した」とは、製品の本体、容器、包装などに表示を付したこと、あるいは製品の情報を開示する説明書、添付文書、宣伝物、その他の印刷物などに表示を付したことを意味する。皮膚バリア機能を維持又は改善させるために用いられる旨の表示においては、本発明の経口用組成物を投与もしくは摂取することにより皮膚バリア機能が維持又は改善される機序についての情報を含むことができる。また、皮膚バリア機能の低下に起因する症状や病気の予防又は改善のために用いられること、に関する情報を含むことができる。 The product of the oral composition of the present invention (pharmaceutical product, food and drink) or its instructions may be labeled with an indication that it is used to maintain or improve the skin barrier function. Here, “labeled product or instructions” means that the product body, container, packaging, etc. are marked, or instructions, package inserts, promotional materials, or other printed materials that disclose product information. It means that the display is attached to. The indication to be used to maintain or improve the skin barrier function may include information on the mechanism by which the skin barrier function is maintained or improved by administering or ingesting the oral composition of the present invention. it can. Moreover, the information regarding the symptom resulting from the fall of a skin barrier function, or being used for the prevention or improvement of a disease can be included.
　以下に試験例を挙げて本発明をさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to test examples.
　なお、シワの程度はその重傷度から次の４段階の基準で評価した。 In addition, the degree of wrinkles was evaluated according to the following four levels based on the degree of serious injury.
　スコア０：症状なし
　スコア１：浅いシワ
　スコア２：深いシワ
　スコア３：跡が残る深いシワ
　試験例１　マウス皮膚中タウリン量の老化（加齢）による変化
　５週齢のＨＲ－１系雌性マウス（日本エスエルシー株式会社から購入）を使用し、１群１０匹とし、１２、２４、３６及び４８週齢時に背部皮膚を摘出して、表皮と真皮を剥離し、ＨＰＬＣ法によって組織中のタウリン量を定量した。 Score 0: No symptoms Score 1: Shallow wrinkles Score 2: Deep wrinkles Score 3: Deep wrinkles with traces Test Example 1 Changes in the amount of taurine in the mouse skin due to aging (aging) 5-week-old HR-1 female mice ( Purchased from Nippon SLC Co., Ltd.), 10 animals per group, the back skin was removed at 12, 24, 36 and 48 weeks of age, the epidermis and dermis were peeled off, and the amount of taurine in the tissue by HPLC method Was quantified.
　その結果、１２週齢と比較して、表皮では４８週齢において、真皮では２４週齢から有意なタウリン量の低下が認められた（図１及び２参照）。 As a result, compared with 12 weeks of age, a significant decrease in the amount of taurine was observed at 48 weeks of age in the epidermis and 24 weeks of age in the dermis (see FIGS. 1 and 2).
　試験例２　タウリン経口投与による皮膚中タウリン量の変化
　５週齢のＨＲ－１系雌性マウス（日本エスエルシー株式会社から購入）を使用し、１群１０匹とし、３２週齢まで飼育した後、３％タウリン水溶液を４週間混水投与した。一方、対照群には精製水を投与した。投与終了後、試験例1と同様に皮膚を採取し、皮膚中のタウリン量を測定した。 Test Example 2 Change of Taurine Content in the Skin by Oral Administration of Taurine Using 5-week-old HR-1 female mice (purchased from Japan SLC Co., Ltd.), 10 mice per group, reared up to 32 weeks of age, A 3% aqueous solution of taurine was administered for 4 weeks. On the other hand, purified water was administered to the control group. After administration, skin was collected in the same manner as in Test Example 1, and the amount of taurine in the skin was measured.
　その結果、タウリン投与群では表皮においてタウリン量の有意な増加が認められた（図３参照）。 As a result, in the taurine administration group, a significant increase in the amount of taurine was observed in the epidermis (see FIG. 3).
　試験例３　紫外線照射により低下した皮膚機能に対するタウリン投与の影響
　７週齢のＨＲ－１系雄性マウス（日本エスエルシー株式会社から購入）を使用し、１群１０匹とし、マウス背部に紫外線（照射量７０～１００ｍＪ／ｃｍ２）を週３回、４週間照射した。その間、３％タウリン水溶液を混水投与した。一方、対照群には精製水を投与した。最終投与後に背部皮膚の角層水分量及び経皮水分蒸散量を測定した。 Test Example 3 Effect of Taurine Administration on Skin Function Decreased by Ultraviolet Irradiation Using 7-week-old HR-1 male mice (purchased from Japan SLC Co., Ltd.), 10 mice per group, and ultraviolet rays (irradiation on the back of the mice) A dose of 70-100 mJ / cm 2 ) was irradiated 3 times a week for 4 weeks. Meanwhile, 3% aqueous taurine solution was administered as a mixed water. On the other hand, purified water was administered to the control group. After the final administration, the horny layer moisture content and transdermal moisture transpiration of the back skin were measured.
　その結果、未照射群に対して、紫外線を照射した溶媒投与群で角層水分量の有意な低下、経皮水分蒸散量の有意な増加が認められた。これに対し、タウリン投与群では角層水分量の有意な低下抑制、経皮水分蒸散量の有意な低下作用が認められた（図５及び６参照）。 As a result, a significant decrease in stratum corneum water content and a significant increase in transdermal water transpiration were observed in the solvent-administered group irradiated with ultraviolet light compared to the unirradiated group. On the other hand, in the taurine administration group, significant reduction of stratum corneum water content and significant reduction of transdermal water transpiration were observed (see FIGS. 5 and 6).
　試験例４　紫外線照射により発生するシワに対する、シワ発生前からのタウリン投与の影響
　８週齢のＨＲ－１系雄性マウス（日本エスエルシー株式会社から購入）を使用し、１群９～１０匹とし、マウス背部に紫外線（照射量７０～１００ｍＪ／ｃｍ２）を週３回、８週間照射した。その間、３％タウリン水溶液を混水投与した。一方、対照群には精製水を投与した。最終投与後に背部皮膚のシワを上記基準に従って評価し、スコア化した。 Test Example 4 Effect of Taurine Administration Before Wrinkle Generation on Wrinkles Generated by Ultraviolet Irradiation Using 8 week old HR-1 male mice (purchased from Japan SLC Co., Ltd.), 9 to 10 animals per group The back of the mouse was irradiated with ultraviolet rays (irradiation amount 70-100 mJ / cm 2 ) three times a week for 8 weeks. Meanwhile, 3% aqueous taurine solution was administered as a mixed water. On the other hand, purified water was administered to the control group. After the final administration, wrinkles on the back skin were evaluated according to the above criteria and scored.
　その結果、未照射群に対して、紫外線を照射した溶媒投与群でシワスコアの有意な増加が認められた。これに対し、タウリン投与群ではシワスコアの有意な低下作用が認められた（図７参照）。 As a result, a significant increase in wrinkle score was observed in the solvent-administered group irradiated with ultraviolet rays compared to the unirradiated group. On the other hand, a significant lowering effect of wrinkle score was observed in the taurine administration group (see FIG. 7).
　試験例５　紫外線照射により発生したシワに対するタウリン投与の影響
　７週齢のＨＲ－１系雄性マウス（日本エスエルシー株式会社から購入）を使用し、１群１０匹とし、マウス背部に紫外線（照射量７０～１００ｍＪ／ｃｍ２）を週３回、１２週間照射した。紫外線照射開始８週間後から（顕著なシワの発生が確認されてから）、３％タウリン水溶液を４週間混水投与した。一方、対照群には精製水を投与した。最終投与後に背部皮膚のシワを上記基準に従って評価し、スコア化した。 Test Example 5 Effect of Taurine Administration on Wrinkles Generated by Ultraviolet Irradiation Using 7-week-old HR-1 male mice (purchased from Japan SLC Co., Ltd.), 10 mice per group, and ultraviolet rays (irradiation dose on the back of mice) (70-100 mJ / cm 2 ) was irradiated 3 times a week for 12 weeks. From 8 weeks after the start of ultraviolet irradiation (after the occurrence of significant wrinkles was confirmed), a 3% taurine aqueous solution was administered as a mixed water for 4 weeks. On the other hand, purified water was administered to the control group. After the final administration, wrinkles on the back skin were evaluated according to the above criteria and scored.
　その結果、未照射群に対して、紫外線を照射した溶媒投与群でシワスコアの有意な増加が認められた。これに対し、タウリン投与群ではシワスコアの有意な低下作用が認められた（図８参照）。
［総括］
　試験例１－３の結果から、タウリンの経口投与により、老化マウスの皮膚中のタウリン量が増加し、それに伴い、皮膚（表皮・真皮）の角層水分量が増加し、経皮水分蒸散量が減少し、老化マウスの皮膚バリア機能が顕著に改善されることが確認された。 As a result, a significant increase in wrinkle scores was observed in the solvent-administered group irradiated with ultraviolet light compared to the unirradiated group. In contrast, in the taurine administration group, a significant wrinkle score lowering effect was observed (see FIG. 8).
[Summary]
From the results of Test Example 1-3, the amount of taurine in the skin of aging mice was increased by oral administration of taurine, and accordingly, the amount of stratum corneum water in the skin (epidermis / dermis) increased, and the amount of transdermal moisture transpiration It was confirmed that the skin barrier function of aging mice was significantly improved.
　また、試験例４の結果から、タウリンの経口投与により、老化マウスの皮膚のシワの生成が顕著に抑制されることが確認された。 Further, from the results of Test Example 4, it was confirmed that the oral administration of taurine significantly suppresses the generation of wrinkles on the skin of aging mice.
　さらに、試験例５の結果から、タウリンの経口投与により、老化マウスの皮膚のシワが顕著に改善されることが確認された。 Furthermore, from the results of Test Example 5, it was confirmed that the wrinkles of the skin of aging mice were remarkably improved by oral administration of taurine.
　なお、シワの生成には、真皮中のコラーゲンやエラスチンの量的・質的変化が関与していることが知られているため、経口的に摂取された有効成分のタウリンがこれらの変化を抑制することによって、シワの生成を抑制し、又は生成したシワの改善に寄与していると考えられる。 Since wrinkle formation is known to involve quantitative and qualitative changes in collagen and elastin in the dermis, the active ingredient taurine taken orally suppresses these changes. By doing so, it is considered that the generation of wrinkles is suppressed or the improvement of the generated wrinkles is contributed.
　本発明により、皮膚バリア機能の低下を抑制し、又は、破壊された皮膚バリア機能の修復を促進するとともに、老化に基因するシワを予防又は改善する作用を有する経口用組成物を、例えば、内服液剤、ドリンク剤等の水性飲料の形態で提供することを通じて、アンチエイジング産業等の発展に貢献することが期待される。 According to the present invention, for example, an oral composition having an action of suppressing deterioration of skin barrier function or promoting repair of destroyed skin barrier function and preventing or improving wrinkles caused by aging is used, for example. It is expected to contribute to the development of the anti-aging industry and the like by providing it in the form of an aqueous beverage such as liquids and drinks.

Claims (5)

  1. 　タウリンを有効成分として含有することを特徴とする、皮膚バリア機能を維持又は改善するための経口用組成物。 An oral composition for maintaining or improving skin barrier function, comprising taurine as an active ingredient.
  2. 　タウリンを有効成分として含有することを特徴とする、老化による皮膚バリア機能の低下を抑制又は改善するための経口用組成物。 An oral composition for suppressing or improving a decrease in skin barrier function due to aging, comprising taurine as an active ingredient.
  3. 　タウリンを有効成分として含有することを特徴とする、老化によるシワを予防又は改善するための経口用組成物。 An oral composition for preventing or improving wrinkles due to aging, characterized by containing taurine as an active ingredient.
  4. 　水性飲料である請求項１～３の何れか１項に記載の経口用組成物。 The oral composition according to any one of claims 1 to 3, which is an aqueous beverage.
  5. 　ｐＨが２．５～７．０である請求項４に記載の経口用組成物。 The oral composition according to claim 4, wherein the pH is 2.5 to 7.0.
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