JPH09263529A - Epidermal cornification accelerator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an epidermal cornification accelerator which contains a substance relating to silicic acid, has an action to promote the cornification of epidermal cells to restore the barrier function of skin and is effective for atopic dermatitis, psoriasis, xeroderma, skin roughening, dandruff, lip roughening and the like. SOLUTION: This epidermal cornification accelerator contains 0.1-99wt.%, preferably 5-60wt.% of a substance relating to silicic acid, for example, silicic acid, metasilicic acid, orthosilicic acid, as an active ingredient. When this cornification accelerator is adapted to cosmetics or the like, an acid such as citric acid is preferably employed to adjust the pH to 2-10. The does as a skin preparation for external use or as a cosmetic is percutaneously 1-50mg every application in a formulation. When a bath article is formulated, the dose of the accelerator is 1-5,000mg/l in the bath water. When it is added to a cell culture system, the dose is 1-100,000μM.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a silicic acid-related substance,
For example, the present invention relates to a skin keratinization promoting agent containing silicic acid, metasilicic acid, orthosilicic acid, water glass and the like as active ingredients. More specifically, it improves the skin barrier function by promoting keratinization of epidermal cells, and is effective in improving various skin diseases such as atopic dermatitis, psoriasis, psoriasis, rough skin, scalp dandruff, and rough lip. The present invention relates to an epidermal keratinization promoting agent containing a silicic acid-related substance or a salt thereof as an active ingredient.

[0002]

2. Description of the Related Art The stratum corneum of a healthy skin epidermis has an excellent barrier function to prevent water evaporation in the body and to prevent foreign substances such as foreign antigens from entering the body and to transmit external stimuli to the body. And plays an important role in biological defense. On the other hand, in various skin diseases such as atopic dermatitis, psoriasis, xeroderma, rough skin, scalp dandruff, and rough lip, it is known that the formation of a healthy stratum corneum is hindered (J . Soc. Cosmet. Chem. Japan, 23
Vol. 1, No. 5, p. 1989).

[0003] The hypoplasia of the stratum corneum, that is, parakeratosis, causes a decrease in the barrier function of the skin, which facilitates the evaporation of water, the invasion of foreign substances, and the transmission of external stimuli to the body. It is thought to be related to the induction or deterioration of various skin diseases.

[0004] In order to prevent such skin diseases and maintain healthy skin, it is conceivable to normalize skin troubles by administering certain components. Conventionally,
As a main method for the above purpose, it has been practiced to prevent the skin from drying out and give it moisture by administering a moisturizing component.

[0005] However, the above-mentioned conventional method generally replenishes water on the keratinous surface or partially replenishes moisturizing components, and the effect is only temporary, and the effect of restoring the skin barrier is sustained. (Toshiyuki Takemura:
Pharmacia, vol. 28, page 1, 1992), and a solution to this problem has been desired.

[0006]

In view of the above circumstances, the present inventors have diligently investigated the search in cultured epidermal cells with the intention of promoting keratinization of epidermal cells themselves, and as a result,
This effect was found on a silicic acid-related substance, and the present invention has been completed, and the purpose thereof is to promote keratinization of epidermal cells, atopic dermatitis, psoriasis, xerosis, rough skin, It is intended to provide an agent for promoting keratinization of the epidermis, which has various skin diseases such as dandruff on the scalp and rough lips, and has a barrier function recovery effect.

[0007]

The above object is achieved by an epidermal keratinization promoting agent characterized by containing a silicic acid-related substance.

[0008]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The configuration of the present invention will be described below in detail.

Examples of the silicic acid-related substances used in the present invention include silicic acid, metasilicic acid, orthosilicic acid, metadisilicic acid, metatrisilicic acid, water glass, or their sodium salts, potassium salts, magnesium salts, Examples thereof include salts such as aluminum salts and calcium salts, and specific examples include sodium metasilicate, potassium silicate, sodium orthosilicate and the like.

Silicic acid is insoluble in water, metasilicic acid, orthosilicic acid, metadisilicic acid and metatrisilicic acid exist only in solution, silicic acid, metasilicic acid, orthosilicic acid and metadisilicic acid. Since the acid and the magnesium salt of meta-trisilicic acid are also insoluble in water, sodium metasilicate, potassium silicate, sodium orthosilicate, and water glass are easy to use as the epidermal keratinization promoter of the present invention.
More preferable.

When the epidermis keratinization promoting agent of the present invention is applied to cosmetics and the like, an acid is further contained in addition to these.
An epidermal keratinization promoter whose pH is adjusted to 2 to 10 is preferable.

The acid used to adjust the pH is
Examples thereof include acidic amino acids such as citric acid, acetic acid, malic acid, organic acid, formic acid and aspartic acid, hydrochloric acid and sulfuric acid.

The form of the epidermal keratinization promoter of the present invention is a silicic acid-related substance, or a product obtained by diluting these substances with water, neutralized water, acidic water, or the like, or a preservative such as methylparaben in addition to the diluted product. And the like are added appropriately.

The epidermal keratinization promoting agent of the present invention, depending on the purpose of use, is a commonly used known medically acceptable component, or a commonly used known component such as a skin external preparation, a cosmetic or a bath agent. Can be incorporated into a composition for transdermal application.

The amount of the epidermal keratinization promoting agent of the present invention to be added to the composition varies depending on its use and dosage form, but is based on the total amount of the external preparation for skin, cosmetics, bath agents and the like.
1 to 99% by weight is preferable, and 5 to 60% by weight is particularly preferable.

The dose of the epidermal keratinization promoting agent of the present invention varies depending on the age, body weight, symptom or administration method of the patient or person with parakeratosis, but when applied to a skin external preparation or a cosmetic composition. 1 to 50 per dose by transdermal administration
When it is formulated so that it can be administered in mg, or when it is applied to a bathing agent, it is preferable to formulate it so that the concentration in the hot water bath is 1 to 5000 mg / l when it is bathed for 10 to 30 minutes per day. When the epidermal keratinization-accelerating agent of the present invention is used by adding it to a cultured cell line, it is preferably added at 1 to 100,000 μM.

[0017]

The present invention will be described below in detail with reference to examples. Prior to the examples, a keratinization acceleration test of a silicic acid-related substance, an animal model rough skin inhibition test, and an efficacy test in a dry skin paneller will be described.

Test Example 1 (Keratinization promotion test) (1) Method (a) Cultured epidermal cells Commercially available human normal epidermal cells (manufactured by Cascade Biology) were used.

(B) Cell culture medium As the medium, MCDB153HAA medium (manufactured by Kyokuto)
On the basis of this, hydrocortisone (0.5μ
M), ethanolamine (0.1 mM), phosphoethanolamine (0.1 mM), insulin (5 μg / m
l) and EGF (epidermal growth factor: 10 ng / m
The K-GM medium to which 1) was added was used. In addition, during cell culture, BPE (bovine pituitary extract) (Cascade
Biology) was added (4 μl / ml medium) and used.

(C) Preparation of Hepes buffer Hepes 7.15 g, glucose 1.8 g, potassium chloride 0.22 g, sodium chloride 7.7 g, and disodium hydrogen phosphate dodecahydrate 0.27 g were dissolved in purified water. Then, the pH was adjusted to 7.4 with a 1N aqueous sodium hydroxide solution, and the volume was adjusted to 1 l.

(D) Cell culture The number of normal human epidermal cells was adjusted to 1 × 10 ⁴ cells / ml in K-GM medium (BPE added), and 1 ml each was placed on a 24-well collagen-coated plate (Corning). The seeds were seeded and statically cultured at 37 ° C. for 4 days in an atmosphere of 95% air (V / V) -5% (V / V) carbon dioxide gas. After that, K-GM medium (B containing final concentrations of 0.01, 0.1, and 1 mM of sodium metasilicate, water glass, sodium orthosilicate, potassium silicate, and purified water as a control (B
PE addition: 0.4 μl / ml medium), and change to 95%
Air (V / V) -5% (V / V) in an atmosphere of carbon dioxide gas,
Static culture was carried out at 37 ° C for 7 days. During this period, the medium was replaced every two days.

(F) Measurement of Corneal Membrane Forming Ability After the culture, the culture supernatant is removed by suction, and the cells are washed with Hepes buffer to
After washing twice, cells were detached by trypsinization. Then, the remaining cells were allowed to stand at 37 ° C./2 hours in 500 μl medium containing 20 μg / ml calcium ionophore (A23187) and 1.25 mM calcium ion, and further 1% SDS (sodium lauryl sulfate) / 20
The cells were lysed in a mM DTT (dithiothreitol) solution and heat-treated at 100 ° C for 5 minutes. After the heat treatment, the number of insolubilized cells (the number of keratinized cells) was counted.

(2) Results Table 1 shows the effects of the silicic acid-related substances used in Test Example 1. The number of keratinized cells of epidermal cells was increased in the culture containing the silicic acid-related substance, as compared with the control without addition of the drug, and it was found that the silicic acid-related substance promotes keratinization of the human epidermal cells themselves.

[0024]

[Table 1]

Test Example 2 (Rough skin suppression test) (1) Method Using a mouse rough skin model induced by retinoic acid, the preventive / ameliorating effects of sodium metasilicate and purified water as a comparison against rough skin were examined.

Hairless mice (hr-1
(Male of the strain) was purchased and raised until 10 weeks of age, and then the experiment was started with 5 animals per group.

As a method for producing rough skin, 400 μg / ml dissolved in ethanol was added to the back of the hairless mouse.
50 μl of retinoic acid was applied for 3 days to induce rough skin.

In examining the effect of suppressing skin roughness, 0.
5% -N-NP-15 (Nonionic polyoxyethylene (15E.
O.) 2 mM sodium metasilicate dissolved in nonylphenyl ether, Nikko Chemical) or 0.5% -N-NP-15 as a control group was applied to the back of each hairless mouse group 50 μl once a day continuously. It was applied for 12 days. The application schedule was 7 days before application of retinoic acid, 3 days of application of retinoic acid, and 2 days after application.
During the retinoic acid application period of 3 days, the application site of retinoic acid was the same as the application site of sodium metasilicate or purified water. Therefore, sodium metasilicate or purified water was applied 6 hours after the application of retinoic acid.

The transepidermal water loss (TEWL) was measured by A
MU-3 (manufactured by Forsion Co., Ltd.) was used, and the amount of water transpiration (mg / cm ² / min) was shown. The measurement time was set just before the start of application and on the third day after the start of application.

(2) Results Table 2 shows the rough skin improving effect of sodium metasilicate used in Test Example 2. By applying retinoic acid to the back of hairless mice, the control group was treated with TE within 3 days after the start of application.
Although the increase in WL was observed about 9 times, the increase in TEWL was suppressed to about 5 times in the sodium metasilicate application group. It can be said that this indicates that sodium metasilicate suppressed the occurrence of skin roughness due to retinoic acid, and showed the effect of improving and preventing skin roughness.

[0031]

[Table 2]

Test Example 3 With respect to a bathing agent containing sodium metasilicate, the bathing effect of a panelist who complains of rough skin was examined as follows.

100 g of the bath salt of Application Example 17 was added to 18 L of hot water at 41 ° C. For comparison, 18 L of hot water was used. For three female panelists who complain of dry skin and rough skin such as lumpiness, soak their right arm in hot water of Application Example 17 and their left arm in comparative hot water for 5 minutes once a day for 4 weeks. I took a partial bath. Before and after the 4-week test, the skin stratum corneum water content was measured by SKI.
With CON-200, the condition of skin desquamation was examined by observing it with a magnifying video camera, and evaluated according to the criteria shown in Table 3 below.

Scores of the observed peels, clefts, and scales

[0035]

[Table 3]

The results of evaluating the bathing effect are shown in Table 4.
When the bath salt containing sodium metasilicate was used, it was observed that the skin groove on the skin surface became clearer and the amount of desquamation decreased compared to the case of the hot water, and the rough skin was improved.

[0037]

[Table 4]

Example 1 12.2 mg of sodium metasilicate was dissolved in 9 ml of a 20 mM hydrochloric acid solution, the pH was neutralized with 1N sodium hydroxide, and the volume was adjusted to 10 ml with purified water. It was sterilized by filtration through a nitrocellulose membrane having a pore size of 0.2 μm (manufactured by Advantech Toyo Co., Ltd., DISMIC-25) to obtain an epidermal keratinization promoting agent.

Example 2 Example 1 except that 15.4 mg of potassium silicate was used.
Was prepared in the same manner as described above.

Example 3 A skin keratinization promoting agent was prepared in the same manner as in Example 1 except that 18.4 mg of sodium orthosilicate and 9 ml of 40 mM hydrochloric acid solution were used.

Example 4 An epidermal keratinization accelerator was prepared in the same manner as in Example 1 except that 16.9 mg of water glass was used.

Examples 5-8 The epidermal keratinization promoters of Examples 1, 2, 3 and 4 were diluted 10-fold with 0.1% by weight methylparaben solution to prepare Examples 5, 6, 7 and 8. An epidermal keratinization promoter was prepared.

Application Examples 1 to 4 (lotion) The epidermal keratinization promoting agent of any of Examples 1, 2, 3 and 4, sodium lauryl sulfate and purified water were prepared in the amounts shown in Table 5, and the mixture was applied in a hot water bath at 80. The mixture was heated to ℃ and mixed, while salix beeswax, cetanol and concentrated glycerin were adjusted to the amounts shown in Table 5, heated to 80 ℃ and mixed, and the mixture was heated to 80 ° C. Was gradually added with stirring, and the mixture was vigorously stirred (2500 rpm) for 2.5 minutes with a homogenizer (TOKUSHUKIKAKOGYO). The mixture was gradually cooled to room temperature with stirring to obtain lotions of Application Examples 1, 2, 3 and 4 containing 6 mM of metasilicate in 100 g.

[0044]

[Table 5]

Application Examples 5 to 8 (Cream) The ingredients shown in Table 6 are uniformly mixed and dissolved at about 80 ° C. to about 80 ° C.
After adding and emulsifying the components uniformly mixed and dissolved in the above, the components uniformly mixed and dissolved at about 50 ° C. are added, and the mixture is cooled to about 30 ° C. , 8 were prepared.

[0046]

[Table 6]

Application Examples 9 to 12 (Oily Hair Artnic) 3 of the epidermal keratinization promoting agents of Examples 5, 6, 7 and 8
Using 7.2 g, according to the composition of Table 7, the hydrophilic component and the lipophilic component were mixed and stirred to obtain oily hair artic acids of Formulation Examples 9, 10, 11, and 12.

[0048]

[Table 7]

Application Examples 13 to 16 (Hair Cream) The hydrophilic components shown in the following Table 8 containing the epidermal keratinization promoter of any of Examples 1, 2, 3 and 4 were uniformly mixed and dissolved at about 80 ° C. After adding and emulsifying into the lipophilic component which has been uniformly mixed and dissolved at about 80 ° C., the perfume component is added at about 50 ° C. and stirring is continued until it reaches about 30 ° C.
4, 15, 16 hair creams were prepared.

[0050]

[Table 8]

Application Example 17 A bathing agent composition having the formulation shown in Table 9 was prepared by an ordinary method of mixing powders, and 48.95 g of sodium metasilicate was prepared.
100 g of a bathing agent containing was prepared.

[0052]

[Table 9]

[0053]

As described above, according to the present invention, keratinization of epidermal cells within the skin epidermis layer is promoted, and the skin barrier function is improved, thereby starting atopic dermatitis and psoriasis.
It is clear that an epidermal keratinization promoter effective for improving skin diseases such as xerosis, rough skin, dandruff of the scalp, and rough lips can be provided.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number in the agency FI Technical display location A61K 7/50 A61K 7/50 (72) Inventor Tatsuo Oshima 5-3, Kotowara, Odawara-shi, Kanagawa No. 28 Kanebo Co., Ltd. Cosmetic Research Laboratory (72) Inventor Toru Matsuo 5-3 28, Kotobuki-cho, Odawara-shi, Kanagawa Kanebo Co., Ltd. Cosmetic Research Laboratory

Claims (6)

[Claims] 1. An epidermal keratinization promoting agent comprising a silicic acid-related substance. 2. The epidermal keratinization promoting agent according to claim 1, wherein the silicic acid-related substance is selected from the group consisting of silicic acid, metasilicic acid and orthosilicic acid. 3. The epidermal keratinization promoting agent according to claim 1, wherein the silicic acid-related substance is selected from the group consisting of sodium metasilicate, potassium silicate, sodium orthosilicate, and water glass. 4. An epidermal keratinization promoting agent comprising a silicic acid-related substance and an acid. 5. The epidermal keratinization promoting agent according to claim 4, wherein the silicic acid-related substance is selected from the group consisting of silicic acid, metasilicic acid and orthosilicic acid. 6. The epidermal keratinization promoting agent according to claim 4, wherein the silicic acid-related substance is selected from the group consisting of sodium metasilicate, potassium silicate, sodium orthosilicate, and water glass.