JP2009084244A - Skin barrier function improving agent and the like - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a food or a drug which exhibits excellent skin function-improving benefits such as a skin barrier function-improving benefit, a moisturizing benefit, a ceramide increase, and a keratinization ameliorating benefit. <P>SOLUTION: Provided are a skin barrier function-improving agent, a skin ceramide-increasing agent, a skin moisturizing function-ameliorating agent, a keratinization ameliorating agent, etc., each of which contains as an active ingredient, a free 10-36C saturated fatty acid or a salt thereof. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a skin barrier function improving agent for improving skin barrier function, a skin moisturizing function improving agent for improving skin moisturizing function, a skin ceramide increasing agent for increasing skin ceramide, and an angle for promoting keratinization of epidermis. It relates to chemical improving agents.

  The stratum corneum of the skin has a barrier function that prevents transpiration of moisture from the body and prevents irritation from the outside world. If the stratum corneum is poorly formed due to keratinization, or if the barrier function is impaired by ultraviolet rays, surfactants, drying, mechanical irritation, active oxygen, residual chlorine in tap water, etc., dry skin, atopic dermatitis, skin roughness It is known to induce etc.

  Conventionally, as means for improving the keratinization of the epidermis, external use of amine derivatives has been reported (for example, see Patent Document 1), and as means for improving the barrier function, plant components such as arnica and turmeric (for example, A method of externally administering polysaccharides such as Pamakin and Pahimaran (for example, see Patent Document 3) has been reported, and is one of the main components of the stratum corneum and is important for skin barrier function As a means for promoting the production of eucalyptus, a method of externally administering eucalyptus, cattail, bonito and the like has been reported (for example, see Patent Document 4). In addition, it has been reported that oral intake of ceramide improves the skin moisturizing function (see, for example, Non-Patent Document 1).

However, it is difficult to apply the preparation for external use to the whole body every day, and it may cause inflammation, irritation, allergies and the like. On the other hand, oral ingestion can be easily applied to the whole body, but ceramide oral ingestion is not necessarily effective.
Therefore, there is a demand for a method of sufficiently exerting skin moisture retention / barrier function, keratinization improvement and increase in ceramide by ingestion.

On the other hand, DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) are known as medium- to long-chain fatty acids having physiological activity, and lipids containing them are used for the prevention of cardiovascular diseases. Yes. Recently, lipids containing palmitoleic acid have the effect of increasing the amount of antibacterial fatty acids in the epidermis (see, for example, Patent Document 5), or lipids containing DGLA (dihomo-γ-linolenic acid) It has an effect of improving skin diseases (for example, see Patent Document 6), and an action of promoting the maturation of corneocytes to lipids containing α-linolenic acid (for example, see Patent Document 7). .
However, it is not known that medium to long-chain saturated free fatty acids have skin barrier function improvement, moisturizing action, and keratinization improving action.
Japanese Patent No. 2699132 JP 2003-171310 A JP 2002-275046 A Japanese Patent No. 3816262 JP-T-2004-504044 International Publication No. 2006/085687 Pamphlet JP 2004-35456 A Fragrance Journal 123 (1), 81 (1995)

  The present invention relates to providing a food or pharmaceutical product that exhibits excellent skin function improving effects such as a skin barrier function improving effect, a moisturizing function improving effect, a ceramide increasing effect, and a keratinization improving effect.

  When the present inventors examined the component which exhibits a skin function improvement effect, the saturated free fatty acid which has a specific carbon number increases a stratum corneum amount by oral ingestion, and has a skin barrier function and a moisturizing function. The present invention has been found to be useful as a food or a medicine having an action of improving and further an action of improving keratinization and exhibiting the function.

That is, the present invention relates to the following inventions 1) to 9).
1) A skin barrier function improving agent containing a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.
2) A skin ceramide increasing agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.
3) A skin moisturizing function improver comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.
4) A keratinization improver comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.
5) A lolicrin expression promoter containing a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.
6) 1) skin barrier function improving agent, 2) skin ceramide increasing agent, 3) skin moisturizing function improving agent, 4) keratinization improving agent or 5) loricrin expression promoter for oral administration.
7) A food for improving skin barrier function, comprising a skin barrier function improving agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.
8) A skin moisturizing food containing a skin moisturizing function improving agent containing a C10-36 saturated free fatty acid or a salt thereof as an active ingredient.
9) A food for improving keratinization containing a keratinization improving agent comprising a C10-36 saturated free fatty acid or a salt thereof as an active ingredient.
10) A food for increasing skin ceramide containing a skin ceramide increasing agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.

  According to the skin barrier function-improving agent, skin ceramide increasing agent, skin moisturizing function improving agent, keratinization improving agent, etc. of the present invention, whole body skin ceramide can be increased by ingestion, improving and strengthening the skin barrier function. In addition, the moisture content of the skin can be increased, and the formation of the stratum corneum can be normalized.

As a C10-36 saturated free fatty acid in this invention, a C12-C30 thing is more preferable, and a C16-C24 thing is more preferable.
Saturated fatty acids having 10 to 36 carbon atoms are contained in vegetable oils and animal fats and most of them are present in the form of triglycerides, but the effects of the present invention cannot be obtained in the state of such triglycerides, and free fatty acids. Or it is exhibited in the state of the salt (refer the below-mentioned Example).
Examples of the saturated free fatty acid of the present invention include capric acid (C10), lauric acid (C12), myristic acid (C14), pentadecylic acid (C15), palmitic acid (C16), margaric acid (C17), and stearic acid. (C18), arachidic acid (C20), behenic acid (C22), lignoceric acid (C24), serotic acid (C26), montanic acid (C28) and the like. Among these, those having 12 to 24 carbon atoms are preferable. Palmitic acid, stearic acid, arachidic acid, behenic acid and lignoceric acid are more preferred.

Examples of the salts of these saturated free fatty acids include metal salts such as sodium salt and potassium salt, amino acid salts such as arginine salt and lysine salt, amine salts such as triethanolamine salt and monoethanolamine salt, etc. It may be.
Such saturated free fatty acids or salts thereof may be used alone or in combination.

  The saturated free fatty acid of the present invention is isolated and purified from vegetable oils or animal fats by a known method, and lipids such as glycerolipids, phospholipids and fatty acid esters are hydrolyzed by a known method. Can be obtained.

The saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof according to the present invention has an action of increasing the amount of horny layer ceramide and the amount of water and improving the barrier function of the skin, as shown in Examples below. Therefore, the saturated free fatty acid or a salt thereof of the present invention is a skin ceramide increasing agent, a moisturizing effect, a skin moisturizing function improving agent that exhibits a preventive / improving effect on dry skin, etc., and an improvement or improving effect on the skin barrier function, To produce a skin ceramide increasing agent, a skin moisturizing function improving agent, or a skin barrier function improving agent, which can be a skin barrier function improving agent that exhibits prevention and improvement of rough skin due to drying, prevention and improvement effects of atopic dermatitis, etc. Can be used.
In addition, the saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof of the present invention has an action of increasing the expression of loricrin. Loricrin is an insoluble protein with a molecular weight of 26 kDa that is expressed in the final stage of the keratinization process and is a major component of the confined cell envelope. It is known that loricrin is taken into the confined cell envelope by the action of transglutaminase 1. Loricrin knockout mice have been reported to have delayed skin barrier formation during embryonic development (Koch PJ, et al., J Cell Biol 2000). Therefore, the saturated free fatty acid or a salt thereof of the present invention can be a loricrin expression promoter and a keratinization improving agent, and can be used to produce a loricrin expression promoter and a keratinization improving agent.
Such skin barrier function improving agents, skin ceramide increasing agents, skin moisturizing function improving agents, keratinization improving agents and loricrin expression promoters (hereinafter also referred to as “skin barrier function improving agents”) are used as foods or oral medicines, etc. It can be used. Here, as food, in addition to general food and drink, food for improving the skin barrier function, improvement of skin moisturizing function, increase of ceramide in skin, prevention / improvement of dry skin, prevention / improvement of rough skin, Special uses such as beauty foods, health foods, foods for specified health use such as prevention and improvement of atopic dermatitis, promotion of loricrin, keratinization improvement, prevention and improvement of acne and dandruff, prevention and improvement of rough skin after sunburn It can be a food and drink.

  Examples of food forms include drinks such as drinks, powdered drinks such as powdered juice, candy, drops, jelly, cookies, chocolates, cakes, yogurt, gums and other confectionery, seasonings, cooking oils, dairy products, Examples include bread and processed rice. Moreover, it is good also as beauty foods, health foods, etc., such as a tablet (tablet), a capsule, and a granule. Moreover, it is good also as food for pets, such as a dog, a cat, and a hamster.

  Such foods include, for example, additives such as sweeteners, colorants, antioxidants, vitamins, fragrances, minerals, food materials such as proteins, lipids, carbohydrates, carbohydrates, dietary fibers, and the like, with the above carbon number of 10 It can be prepared by mixing ˜36 saturated free fatty acids and preparing various food forms according to conventional methods.

  Examples of the administration form when the skin barrier function improving agent of the present invention is used as a pharmaceutical include oral administration using tablets, capsules, suspending agents, syrups and the like. For the preparation of such a pharmaceutical preparation, the free fatty acid of the present invention or a salt thereof alone or in combination with other pharmaceutically acceptable excipients, binders, extenders, disintegrants, surfactants, etc. Can be used.

  The intake or dose of the skin barrier function improving agent or the like of the present invention is appropriately selected depending on the form, age of the intake person, sex, and other conditions, etc., but usually a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof. As a matter of course, it may be about 100 μg to 100 mg, preferably about 1 mg to 40 mg per kg body weight per day, and can be taken and administered once a day or divided into 2 to 4 times a day.

Example 1 Preparation of fatty acid-containing emulsion An emulsion having the composition shown in Table 1 was prepared. That is, a fatty acid or triglyceride (comparative example) and an emulsifier (sucrose fatty acid ester: DK ester F-160 (Daiichi Kogyo Seiyaku), egg yolk-derived phosphatidylcholine (Sigma)) are dissolved in chloroform, and the solvent is distilled off under reduced pressure. Thus, a lipid film was produced. Thereafter, an aqueous solution of 2% bovine serum albumin (purity 98%, initial fractionation by heat shock) (Sigma) was added and emulsified by sonication (final fatty acid concentration 2%). In the control group, the fatty acid was replaced with a 2% albumin aqueous solution to prepare an emulsion. The prepared emulsion was stored at -20 ° C.

Example 2 Skin barrier function improving effect, stratum corneum water content increasing effect, ceramide content increasing effect Females of 6-week-old HR1 hairless mice were used in the experiment. For one week before the start of the experiment, a basic diet (solid feed containing AIN-76A (Oriental Bioservices)) and free intake of water were used for preliminary breeding. After grouping according to body weight (10 animals in each group), the emulsion shown in Table 1 was administered every day for 2 weeks (the basic diet and drinking water during the experiment were the same as in the preliminary breeding).
For administration, an emulsion having a fatty acid concentration of 2%, an emulsion having a fatty acid equivalent of 2% for the comparative example, and a control emulsion were administered once / day using a sonde needle under ether anesthesia. The dose per animal was 0.2 ml / day of emulsion (fatty acid dose of 4 mg / day).

1) Skin barrier function (transdermal moisture transpiration: TEWL)
Two weeks after continuous administration of the emulsion, the TEWL value was measured under Nembutal anesthesia (TewameterTM210, manufactured by CK electronic GmbH: 3 backs of mice). From this measurement, an average value for each individual and an average value for each group were obtained.
2) stratum corneum moisture content (conductance)
Ten back skins were measured with SKICON-200 (IBS), and an average value for each individual and an average value for each group were obtained.
3) Amount of ceramide (amount of ceramide per 1 mg of stratum corneum):
Hairless mice (8 mice per group) administered with the emulsion for 2 weeks were killed and the dorsal skin was peeled off. After heating in a 60 ° C. water bath for 1 minute, the dermis was removed. Immediately, the epidermis was treated in a trypsin solution at 37 ° C. for 1 hour to remove viable epidermis cells to obtain a stratum corneum. After lyophilization, the stratum corneum weight was measured, and the lipid was determined by the Bligh and Dyer method ("Biochemical Experimental Method 9 Introduction to Lipid and Lipid Oxide Analysis" edited by Yoshio Miyazawa and Yasuo Fujino, p45, revised on January 30, 2000) The ceramide was separated by TLC method and colored with 10% copper sulfate / 8% phosphoric acid aqueous solution. The amount of ceramide in the stratum corneum was determined from a calibration curve of standard substances (Ceramides with non-hydroxy fatty acid and Ceramides with hydroxyl fatty acid (both from Sigma)).
The results are shown in Table 2.

  The stratum corneum shown by the increase in the amount of horny layer ceramide and the increase in conductance by ingestion of the product of the present invention containing free fatty acid compared to the control food ingestion group not containing free fatty acid and the comparison product administration group that is glycerolipid A significant improvement effect was observed in the barrier function indicated by a marked increase in water content and a decrease in TEWL.

Example 3 Quantitative expression of loricrin After killing hairless mice (10 mice in each group) to which the emulsions of control product 4 of the present invention and comparative product 2 were continuously administered for 2 weeks, the dorsal skin was peeled to remove subcutaneous fat. Thereafter, 1 cm square skin was collected and immersed in RNAlater solution (QIAGEN). RNA was collected from the skin tissue using an RNA easy mini kit (QIAGEN), and 1 μg of RNA was reverse-transcribed at 50 ° C. using Superscript III (Invitrogen). Quantitative expression of loricrin is performed using Real-Time PCR (Applied Biosystems: 7500 Fast Real-Time PCR System), corrected with the value of GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) as an internal standard, and the expression level of loricrin is calculated. (TaqMan Gene Expression Assays: loricrin Mm01219255_m1 GAPDH: Mm99999915_g1).
As shown in FIG. 1, the product of the present invention containing a saturated free fatty acid was found to increase loricrin expression.

The graph which shows the expression level of loricrin.

Claims (10)

  A skin barrier function improving agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.   A skin ceramide increasing agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.   A skin moisturizing function improving agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.   A keratinization improving agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.   A loricrin expression promoter comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.   The skin barrier function improving agent according to claim 1 for oral administration, the skin ceramide increasing agent according to claim 2, the skin moisturizing function improving agent according to claim 3, the keratinization improving agent according to claim 4, or the claim 5 The described loricrin expression promoter.   The food for skin barrier function improvement containing the skin barrier function improving agent which uses a C10-36 saturated free fatty acid or its salt as an active ingredient.   A skin moisturizing food containing a skin moisturizing function improving agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.   A food for improving keratinization, containing a keratinization improving agent comprising a C10-36 saturated free fatty acid or a salt thereof as an active ingredient.   A food for increasing skin ceramide containing a skin ceramide increasing agent comprising a saturated free fatty acid having 10 to 36 carbon atoms or a salt thereof as an active ingredient.

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