JPH09124488A - Epidermal keratinization-promoting agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an epidermal keratinization-promoting agent effective for the improvement of dermal diseases such as an atopic dermatitis, psoriasis, xeroderma, symptomatic dandruff in head skin and further roughness in lip. SOLUTION: This epidermal keratinization promoting agent contains an α-ethylglycoside. As the α-ethylglycoside used, α-ethylglucose (ethyl α-D- glucopyranoside), α-ethylgalactose, α-ethylmannose, α-ethylallose, α-ethylaltrose, α-ethylgulose, α-ethyltalose, α-ethylxylose, α-ethylarabinose, α-ethylmaltose and α-ethylcellobiose are cited.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to the promotion of keratinization of epidermal cells inside the skin epidermal layer and improvement of the skin barrier function, thereby causing atopic dermatitis, psoriasis, psoriasis and dandruff of the scalp. The present invention relates to an agent for promoting keratinization of the epidermis, which is effective for alleviating various skin diseases such as dermatosis and rough lip.

[0002]

BACKGROUND OF THE INVENTION The stratum corneum in the epidermis of the skin plays a series of physiological roles such as moisturizing ability of the skin and physical protection of the living body, and plays an important role in life activities. However, including so-called atopic dermatitis and psoriasis,
Skin diseases such as xeroderma, dandruff on the scalp, and rough lips often prevent the formation of a healthy stratum corneum.

Insufficiency of the stratum corneum on the surface of the skin leads to deterioration of the skin barrier function, facilitating the infiltration of foreign substances from the outside and the evaporation of body substances such as water, resulting in the initiation or deterioration of various skin diseases. Conceivable.

[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.

However, the above-mentioned conventional method generally replenishes water on the surface of the corneum or partially replenishes the moisturizing component, and the effect is only temporary, and the recovery effect of the skin barrier function is maintained. Cannot be given (Toshiyuki Takemura: Pharmacia, 28, 1, 1992). Therefore, a method for continuously recovering the skin barrier function has been desired.

[0006]

Therefore, the object of the present invention is to improve skin diseases such as atopic dermatitis, psoriasis, psoriasis, scalp dandruff, and rough lip. To provide a keratinization promoting agent for epidermis.

[0007]

In view of the above circumstances, the present inventors have diligently investigated the search for cultured epidermal cells with the intention of promoting keratinization of the epidermal cells themselves, and as a result, α
-Finding that ethyl glycoside has a promoting action,
The present invention has been completed.

That is, the present invention relates to a keratinization promoting agent containing α-ethyl glycoside.

[0009]

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

The α-ethyl glycoside used in the present invention includes α-ethyl glucose (ethyl α-D-glucopy).
ranoside), α-ethylgalactose, α-ethylmannose, α-ethylallose, α-ethylaltrose, α-ethylgulose, α-ethyltalose, α-ethylxylose, α-ethylarabinose, α-ethylmaltose, α- Examples thereof include ethyl cellobiose, and among them, α-ethyl glucose and α-ethyl maltose are particularly preferable. These may be either synthetic or extracted from nature, see for example the literature 'Roczni.
k Chemi., Vol. 49, No. 12, pages 2113 to 2115, 1975, etc.

The composition form of the epidermal keratinization promoting agent of the present invention is not particularly limited, but examples thereof include external preparations for skin such as solutions, ointments, lotions, powders, emulsions and shampoos. Further, as the external preparation for skin, a known external base can be appropriately used.

The blending amount of α-ethyl glycoside in the epidermal keratinization promoting agent of the present invention is preferably 0.001 to 5% by weight based on the total amount of the composition.

[0013]

The present invention will be described in more detail with reference to the following examples. Prior to the examples, a keratinization promotion test, an animal model skin roughness suppression test, an dandruff suppression test, and a lip roughness test will be described.

Test Example 1 (Keratinization promotion test) (1) Test 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 (manufactured by Corning). The seeds were seeded and statically cultured at 37 ° C. for 4 days in an atmosphere of 95% air (V / V) -5% carbon dioxide (V / V). After that, 3,
The medium was replaced with K-GM medium (BPE addition: 0.4 μl / ml medium) supplemented with 10, 30 μg / ml each α-ethyl glucose and 30 μg / ml β-ethyl glucose for comparison, and 95% air (V / V) -5% carbon dioxide (V / V) atmosphere, 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 2
After washing twice, the cells were detached by trypsin treatment and the number of cells in each well was counted with a hemocytometer. After counting the number of cells, the remaining cells were treated with 20 μg / ml calcium ionophore (A
23187) and 1.25 mM calcium ion in 500 μl of the medium, and allowed to stand at 37 ° C. for 2 hours.
% SDS (sodium lauryl sulfate) / 20 mM DT
Lyse cells in T (dithiothreitol) solution and
Heat treatment was performed for 5 minutes. After the heat treatment, the number of insolubilized cells was counted, and the keratinization rate was calculated from the ratio with the number of cells before treatment. The effect of each added drug was evaluated by the ratio of each keratinization rate, where the keratinization rate in the case of no addition as a control was 1.

(2) Results An increase in the keratinization rate of epidermal cells was observed in the α-ethyl glucose-added culture as compared with the control value without addition of the drug (FIG. 1). On the other hand, with β-ethyl glucose, almost no increase in the keratinization rate was observed, and it was found that keratinization was not promoted. Therefore, ethyl glucose is in α form,
It was found that it has an action of specifically promoting keratinization of human epidermal cells themselves.

Test Example 2 (Rough skin suppression test) (1) Test method Using a mouse rough skin model induced by UV irradiation,
The preventive / ameliorating effects of α-ethyl glucose and β-ethyl glucose as a comparison against rough skin were examined.

Hairless mice (hr-1) were used as test animals.
(Male of the strain) was purchased and bred until the age of 9 weeks, and the experiment was started with 5 animals per group.

As a method for creating a rough skin model, irradiation energy of 0.15 J / cm was applied to the back of the hairless mouse.
² (SE lamp: manufactured by Toshiba) was used to irradiate UV-B once.

In examining the effect of suppressing skin roughness, 0.
0.1% dissolved in 5% -Triton X150 (manufactured by Wako Pure Chemical Industries, Ltd.)
Α-ethyl glucose at a concentration of 01% by weight and 0.05% by weight or β-ethyl glucose at a concentration of 0.05% by weight was applied to each hairless mouse group once a day before UV-B irradiation.
It was applied for a day. Even after UV-B irradiation, each group was applied once a day from immediately after irradiation to 3 days in the same manner as before irradiation.
Further, at this time, as a control group, those coated only with ethanol before and after irradiation were placed.

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 By UV-B irradiation of the back of the hairless mouse, the control group showed a 7-fold increase in TEWL 3 days after irradiation, which was 7 times higher than that before the start. An increase in TEWL was suppressed in correlation with the concentration. On the other hand, β
-Ethyl glucose was not suppressed. (FIG. 2) This means that α-ethyl glucose suppressed the induction of skin roughness due to UV-B irradiation, and showed the effect of improving and preventing skin roughness.

Test Example 3 (dandruff suppression test) (1) Test method (a) Method for collecting dandruff After subject's hair was washed on a filter cloth, the filter cloth was ultrasonicated in a 5 l beaker containing ion-exchanged water. The dandruff remaining on the filter cloth was recovered in the ion-exchanged water in the beaker by treating and then stirring. After the hair mixed in the beaker was removed, the dandruff was collected by suction filtration of the ion-exchanged water in which the dandruff floated on a membrane filter (Millipore, 0.45 μm). 10 membrane filters
The dandruff on the filter was collected by rinsing with ml of ion-exchanged water. This was used as an dandruff sample.

(B) Measurement of dandruff amount The dandruff sample was stained with gentian violet brilliant green, and the number of nucleated cells and the number of non-nucleated cells were counted using a hemocytometer under an optical microscope. The total amount of dandruff was the total of the number of nucleated cells and the number of non-nucleated cells in 10 ml of dandruff sample. The nucleated cell rate was shown by the ratio of the number of nucleated cells to the total amount of dandruff.

(C) Preparation of test sample 10% prepared by blending α-ethyl glucose or β-ethyl glucose to a final concentration of 0.05% by weight.
An aqueous ethanol solution was prepared and used as test samples.
As a control sample, 10% aqueous ethanol solution containing no α-ethyl glucose and β-ethyl glucose was used.

(D) Dandruff suppression test The subjects were divided into 3 groups (5 persons in each group), the dandruff of the subjects was collected on the morning of the first day of the test, and the number of nucleated cells and the number of non-nucleated cells were counted. The nucleated cell rate and the total amount of dandruff were calculated. Thereafter, for 40 days, the subject was washed with normal shampoo and rinse every day, and after each hair wash, an appropriate amount of test sample (group 1 and group 2) and control sample (group 3) were externally applied to the scalp. The dandruff of the subject was collected in the morning 40 days later, the number of nucleated cells and the number of non-nucleated cells were counted, and the nucleated cell ratio and the total amount of dandruff were calculated.

(2) Results The relative value of the total amount of dandruff 40 days after the first day of the test was 95 in the group 3 to which the control sample was administered.
%, 65% in group 1 administered with the α-ethyl glucose combination sample, and 90% in group 2 administered with the β-ethyl glucose combination sample. In addition, the nucleated cell rate after 40 days in groups 2 and 3 was the same as that on the first day from the start of the test, but in group 1, a marked decrease in the nucleated cell rate was observed.

Further, shampoos and rinses containing 1% by weight of α-ethyl glucose described in Examples 4 and 5 were prepared and used by 5 test subjects, and compared with the total amount of dandruff on the first day of the test, After 40 days, the total amount of dandruff decreased to 60%. From these results, it was revealed that α-ethyl glucose has an antidandruff effect.

Test Example 4 (Rough Lip Improvement Test) (1) Test Method (a) Judgment of Rough Lip Judgment was made based on subjective symptoms and the number of nucleated cells. Subjects having both skin peeling and dryness as subjective symptoms were designated as group A (15 persons), and subjects not having both subjective symptoms were designated as group B (5 persons). For the number of nucleated cells, keratinocytes were detached from the central part of the lower lip using a cell uptake plate (made by Kanebo, adhesive area 7 mm diameter). The cell uptake plate with the cells attached thereto was stained with gentian violet brilliant green, and the number of nucleated cells within 4 mm ^{2 was} counted at 3 places under an optical microscope, and the average was taken as the number of nucleated cells.

(B) Preparation of test solution An aqueous solution in which α-ethyl glucose or β-ethyl glucose was dissolved was prepared so that the final concentration was 0.1% by weight, and these were used as test samples. Water was used as a control sample.

(C) Lip Roughness Improvement Test The numbers of nucleated cells in Group A and Group B were 13.7 ± 3.3 and 3.7 ± 2.4 (Cells / 4 mm ² ), respectively. Group A is divided into 3 groups of 5 people each.
1, group A-2 and group A-3. Group A-1
Α-Ethylglucose combination sample for Group A-2, β-Ethylglucose combination sample for Group A-2, and Group A
For -3, a control sample was applied to the lips twice a day for 40 days.

(2) Results The number of nucleated cells after 40 days was remarkably reduced in only the group A-1 coated with the α-ethyl glucose-containing aqueous solution, as compared with the number of nucleated cells before the test. Further, improvement of subjective symptoms was observed only in group A-1. From this, it became clear that α-ethyl glucose has a rough lip improving effect. Also, when the α-ethyl glucose-containing lip balm described in Example 6 was used, the same effect was confirmed.

Example 1 0.5 g of α-ethyl glucose (purchased from Tokyo Kasei Co., Ltd.) was dissolved in 100 ml of distilled water, filtered through a membrane (manufactured by Millipore) having a pore size of 0.22 μm, and an aqueous α-ethyl glucose solution was obtained. Got

Example 2 The following hydrophilic component was heated to 80 ° C. in a water bath and gradually added to the mixed lipophilic component described below with stirring. Next, after stirring with a homogenizer to sufficiently emulsify and disperse each component,
The mixture was gradually cooled with stirring to obtain an α-ethyl glucose ointment.

“Hydrophilic component” Methyl paraoxybenzoate 0.1 g Propylene glycol 6.7 g Aqueous solution of Example 1 44.1 g

“Lipophilic component” Squalane 4.7 g White petrolatum 24.0 g Stearyl alcohol 8.7 g Isopropyl myristate 6.0 g Isopropyl monostearate 1.3 g Polyoxyethylene alkyl ether phosphate 2.3 g Glycerin monostearate 2 0.0 g Butyl paraoxybenzoate 0.1 g

Example 3 1 ml of the aqueous solution obtained in Example 1 was added to the following composition, and α-
100 g of lotion containing ethyl glucose was obtained.

Ethanol 10.0 g Lactic acid 0.3 g Sodium citrate 0.1 g Glycerin 2.0 g Preservative, fragrance and surfactant Suitable amount Purified water Remaining amount

Example 4 Shampoo 10 containing α-ethyl glucose as shown below
0 g was obtained.

Α-Ethyl glucose 1.0 g Lauryl polyoxyethylene (3) sulfate sodium salt (30% aqueous solution) 30.0 g Lauryl sulfate sodium salt (30% aqueous solution) 10.0 g Coconut oil fatty acid diethanolamide 0.3 g Glycerin 0.1g Preservatives, fragrances, chelating agents, pH adjusters and pigments Appropriate amount Purified water Remaining amount

Example 5 The following rinse with α-ethyl glucose was used.
0 g was obtained.

Α-Ethylglucose 1.0 g Liquid paraffin 1.0 g Stearyl alcohol 2.5 g Stearyltrimethylammonium chloride 1.0 g Glycerin 3.0 g Preservatives, perfumes and dyes Appropriate amount Purified water Remaining amount

Example 6 100 g of α-ethyl glucose-containing lip cream shown below was obtained.

Α-Ethyl glucose 1.0 g Paraffin 40.0 g Liquid paraffin 26.0 g Isopropyl myristate 10.0 g Lanolin 23.0 g Perfume and antioxidant Suitable amount

[0048]

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 agent for promoting keratinization of the epidermis can be provided, which is effective in improving skin diseases such as xeroderma, scalp dandruff, and rough lip.

[Brief description of the drawings]

FIG. 1 is a diagram showing the effect of α-ethyl glucose in Test Example 1.

FIG. 2 is a graph showing the effect of α-ethyl glucose on ceramide production by epidermal cells in Test Example 2.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Akinori Hara, 5-3 28, Kotobuki-cho, Odawara-shi, Kanagawa, Kanebo Co., Ltd. (72) Inventor Toshio Horikoshi 5-chome, 3-cho, Odawara, Kanagawa No. 28 Kanebo Co., Ltd. Cosmetic Research Institute (72) Inventor Takeshi Ikemoto 5-3 28, Kotobuki-cho, Odawara-shi, Kanagawa Kanebo Co., Ltd. Cosmetic Research Institute

Claims (2)

[Claims] 1. An epidermal keratinization promoting agent, which comprises α-ethyl glycoside. 2. The epidermal keratinization promoting agent according to claim 1, wherein the α-ethyl glycoside is α-ethyl glucose.