JP5219038B2 - Skin keratinization promoter - Google Patents

Description

  The present invention relates to a composition that promotes skin keratinization and is useful for preventing skin aging and improving skin troubles.

The skin exists on the outermost side of the body, and has a role as a barrier against external stimuli such as bacteria. In the skin, epidermal cells change from basal cells to spinous cells, granule cells, and horny cells over about 4 weeks (keratinization), and intercellular lipids and NMF (natural moisturizing factor) in these cells. ), And further, the barrier function is achieved by forming a converged envelope.
However, it is known that the rate of keratinization decreases due to skin aging, etc., and it is said that when the rate of keratinization decreases, skin dullness and rough skin are caused. As substances that promote the keratinization of the skin, herbal medicine extracts such as peanut extract and lotus germ extract have been reported (see Patent Documents 1 and 2).
JP 2006-316028 A JP 2002-68993 A

However, the action of these conventional keratinization promoting components is not sufficient, and the development of a better skin keratinization promoting agent is desired.
Accordingly, an object of the present invention is to provide a skin keratinization promoter useful for improving the barrier function of skin and preventing skin aging.

Therefore, the present inventors have searched for a skin keratinization promoter using the gene expression level of a protein produced as a component of a cornified envelope together with keratinization of the skin as an index. The present invention was completed by finding that it has an effect of enhancing the amount and is useful as a keratinization promoter.
That is, this invention provides the skin keratinization promoter containing the mineral derived from a pearl layer.

  The skin keratinization promoter of the present invention strongly promotes the expression of loricrin, which is produced as a component of a cornified envelope together with skin keratinization, and promotes skin keratinization. Therefore, if the skin keratinization promoter of the present invention is used, the effects of preventing skin aging and improving skin troubles can be obtained.

  The mineral component derived from the pearl layer used in the present invention can be obtained by firing the pearl layer denucleated from the pearl or the pearl layer of the shell, dissolving the mineral with acid or purified water, filtering, and neutralizing. . Minerals derived from the nacre contain calcium, sodium, magnesium, iron, zinc and trace minerals. The composition ratio of the main mineral per dry matter contains 50 to 99 mass%, more preferably 70 to 95 mass% of calcium. Sodium is contained in an amount of 0 to 40% by mass, more preferably 1 to 15% by mass. Magnesium is contained in an amount of 0 to 5% by mass, more preferably 0.01 to 1% by mass. Iron is contained in an amount of 0 to 10% by mass, more preferably 0.5 to 5% by mass. Zinc is contained in an amount of 0 to 5% by mass, more preferably 0.01 to 1% by mass.

  As shown in Examples described later, when a pearl layer-derived mineral is added, the skin-derived cells increase the loricrin gene expression level. Here, loricrin is a component of the peripheral zone, which is a very strong and huge insoluble structure that lines the cell membrane of keratinocytes. Moreover, the mineral derived from a pearl layer has the effect | action which accelerates | stimulates the stratum corneum formation in a 3D skin model. Therefore, the mineral derived from the nacre is useful as a skin keratinization promoter.

  The skin keratinization promoter of the present invention exhibits drug efficacy for oral, injection, and external use, but is preferably used as a skin external preparation. Skin external preparations include skin cosmetics, external quasi-drugs, and medical skin external preparations.

  In addition, the skin keratinization promoter of the present invention includes surfactants, oily ingredients, moisturizers, polymer compounds, ultraviolet absorbers, anti-inflammatory agents used in various pharmaceutical and cosmetic preparations in addition to the above ingredients. , Fungicides, antioxidants, sequestering agents, preservatives, vitamins, pigments, fragrances, water and the like can be blended.

  As the surfactant, any of anionic, cationic, nonionic, natural, and synthetic surfactants can be used, but it is preferable to use a nonionic surfactant in consideration of irritation to the skin. Examples of the nonionic surfactant include glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene glycol. , Polyoxyethylene polyoxypropylene alkyl ether, polyethylene glycol fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, alkylglycoside and the like.

  Examples of the oil component include fats and oils, waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, essential oils, silicone oils, and the like. Examples of the fats and oils include soybean oil, nutka oil, jojoba oil, avocado oil, almond oil, olive oil, cacao oil, sesame oil, persic oil, castor oil, coconut oil, mink oil, beef fat, pork fat and the like, and these Hardened oil obtained by hydrogenation of natural fats and oils and synthetic triglycerides such as myristic acid glyceride and 2-ethylhexanoic acid triglyceride; waxes include, for example, carnauba wax, whale wax, beeswax, lanolin and the like; hydrocarbons For example, liquid paraffin, petrolatum, paraffin microcrystalline wax, ceresin, squalane, bristan etc .; higher fatty acids include, for example, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, Linolenic acid, lanolinic acid, isostearic acid, etc .; Examples of the class alcohols include lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, 2-hexyldecanol, etc .; examples of the esters include cetyl octanoate, triglyceride octanoate, myristyl lactate, cetyl lactate, Examples of essential oils include mint oil, jasmine, isopropyl myristate, myristyl myristate, octyldodecyl myristate, isopropyl palmitate, isopropyl adipate, butyl stearate, decyl oleate, cholesterol isostearate, POE sorbite fatty acid ester, etc. Oil, pepper brain oil, cypress oil, spruce oil, ryu oil, turpentine oil, cinnamon oil, bergamot oil, mandarin oil, ginger oil, pine , Lavender oil, bay oil, clove oil, hiba oil, rose oil, eucalyptus oil, lemon oil, thyme oil, peppermint oil, rose oil, sage oil, menthol, cineole, eugenol, citral, citronellal, borneol, linalool, geraniol, Camphor, thymol, spirantol, pinene, limonene, terpene compounds, etc .; examples of silicone oils include dimethylpolysiloxane. These oily components described above can be used alone or in combination of two or more. In the present invention, among these, myristic acid glyceride, 2-ethylhexanoic acid triglyceride, lanolin, liquid paraffin, petrolatum, paraffin microcrystalline wax, squalane, lauric acid, myristic acid, palmitic acid, linoleic acid, linolenic acid, isostearic acid , Cetyl alcohol, stearyl alcohol, oleyl alcohol, cholesterol, cetyl octanoate, triglyceride octanoate, isopropyl myristate, octyldodecyl myristate, cholesterol isostearate, POE sorbite fatty acid ester, peppermint oil, spruce oil, cinnamon oil, rose Oil, menthol, cineol, eugenol, citral, citronellal, geraniol, pinene, limonene, dimethylpolysiloxane It is preferable to use.

The following components can be further blended in the skin keratinization promoter of the present invention, but the components are not limited thereto.
(A) Dyes: recognized as food additives such as tar dyes I and II dyes, chlorophyll, riboflavin, crocin, safflower, anthraquinone, etc. stipulated in the Ordinance of the Ministry of Health and Welfare such as Yellow No. 4, Blue No. 1, Yellow No. 202, etc. Natural pigments that are used.
(B) Vitamins; vitamin A, vitamin C, vitamin D, vitamin E, etc.
(C) Others: bactericides, preservatives, other ingredients necessary for the preparation, etc.

  The skin keratinization promoter of the present invention can be produced according to a conventional method by adding the optional components to the essential components as necessary, and can be in the form of cream, milky lotion, lotion or the like.

  In the skin keratinization promoter of the present invention, it is preferable to blend 1 μg to 1 g, particularly 10 μg to 100 mg of the pearl layer-derived mineral as the daily dose of the ingredient (in terms of dry matter). Moreover, it is preferable to contain 10 micrograms-10 g / 100g, especially 40 micrograms-1 g / 100g of pearl layer origin minerals in the skin keratinization promoter of this invention.

  EXAMPLES Next, an Example is given and this invention is demonstrated in detail.

Example 1
(Manufacture of pearl layer-derived minerals)
Enucleate Akoyakai pearls and remove the nacreous layer. Next, the pearl layer is crushed and powdered, and the pearl layer is fired (1050 ° C., 2 hours). Add 2 g of the calcined product to 0.85 kg of water and stir at room temperature for 6 hours. The insoluble matter was removed by filtration, and the filtrate was neutralized with dilute hydrochloric acid to obtain a pearl oyster shell mineral solution.
The obtained mineral solution contained 80 mg / 100 mL of calcium, and the mineral composition ratio was calcium: sodium: magnesium: iron: zinc = 89: 8: 0.2: 3: 0.1 .

Example 2
<Test method>
4th generation human foreskin-derived keratinocytes are seeded at 2.25 × 10 ⁵ per well of a 6-well plate and cultured for 3 days (37 ° C., 95% Air, 5% CO ₂ ) to 70-80% confluence. To do. The nacreous mineral is added and incubated for 24 hours, after which the supernatant is discarded to completely lyse the cells. Total RNA is extracted, RNA is reverse transcribed to produce cDNA, and the gene expression level of protein related to keratinization is detected using quantitative real-time PCR.

<Result>
The results are shown in FIG. As a result, it was revealed that pearl minerals increased the gene expression level of loricrin.

Example 3
<Test method>
Keratinocytes are seeded in a 12-well plate and cultured for 3 days (37 ° C., 95% Air, 5% CO ₂ ) in a medium supplemented with ascorbic acid. The pearl layer-derived mineral and calcium chloride are mixed with the non-woven fabric and then placed on a 12-well cell culture surface and cultured. Ten days after sowing, the epidermis tissue was sampled, and after fixing, a paraffin section was prepared, and stained with HE to prepare a specimen.
<Result>
The results are shown in FIG. As a result, it was confirmed that the formation of the stratum corneum lower layer had already started in the skin to which the pearl layer-derived mineral was added, compared with the case in which calcium chloride was added. This indicates that the pearl layer-derived mineral has a keratinization promoting effect.

It is a figure which shows the gene expression level change of the loricrin by the pearl layer origin mineral. It is a figure which shows the keratinization promotion result (A: pearl mineral, B: calcium chloride) using a 3D skin model.

Claims (1)

A lolicrin expression promoter containing a nacreous-derived mineral solution obtained by firing a nacre and dissolving the fired product in acid or purified water, followed by filtration and neutralization .