JP2001354518A - Skin care preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin care preparation exhibiting an excellent epidermis keratinization promotion, dermis collagen synthesis promotion and an anti- oxidizing action, having an excellent safety. SOLUTION: This skin care preparation comprises a marine alga selected from the group consisting of marine algae of the genus Halymenia, Meristotheca, Furcellaria, Chondracanthus skotsbergii and Chondracanthus sandpape or its extract as an active ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an external preparation for skin containing an extremely safe seaweed extract as an active ingredient for promoting keratinization of the epidermis, promoting the synthesis of dermal collagen or having an antioxidant effect.

[0002]

2. Description of the Related Art One of the most important physiological functions of the epidermis is to form a stratum corneum which serves as a barrier against various stimuli from the outside, such as dryness, ultraviolet rays, and other physical and chemical stimuli. No. The keratinocytes forming the stratum corneum are formed one after another by the differentiation of epidermal keratinocytes, and the old keratinocytes detach from the epidermis. However, for some reason this differentiation is inhibited,
Or, when abnormally enhanced, it causes various dyskeratosis such as xeroderma and acne.

[0003] In addition, skin is affected by internal factors such as aging, ultraviolet rays,
Due to external factors such as active oxygen, the functions of the skin, such as contractility, flexibility, and moisturizing properties, which are originally maintained, are impaired, causing various troubles. In general, biological tissues such as skin can rapidly improve functional deterioration and structural changes caused by various factors due to metabolism. However, due to excessive exposure to aging, such as ultraviolet rays, dryness and harmful chemical substances, and the accumulation of injuries in living tissues, the original function is impaired and various troubles occur. Skin suffers from spots, wrinkles, rough skin, and atopic symptoms. One of these troubles, wrinkles, is due to a decrease in the number of cells producing the extracellular matrix of the dermis, aging of cell functions such as a decrease in division rate, a decrease and degeneration of collagen fibers, a decrease in subcutaneous adipose tissue, etc. Occurs due to skin relaxation and loss of elasticity.

[0004] As means for solving these various skin problems, there have hitherto been used a composition for applying a substance such as NMF such as collagen, hyaluronic acid or amino acid, which is lost by various external stimuli or aging, to the skin to supplement it. Compositions containing protective substances for protecting the skin from ultraviolet rays and active oxygen have been the mainstream. However, these do not improve the function of the skin itself, and have not had a sufficient effect.

The present inventors have already found that seaweed that promotes biosynthesis of hyaluronic acid lost by aging (Japanese Patent Laid-Open No.
1871, JP-A-9-176036) and seaweed that inhibits the activity of hyaluronidase (JP-A-9-67266)
In addition, they found an effect of preventing skin aging. As mentioned above,
Various factors are involved in the complexion of skin aging, and other factors also need to be examined.

[0006]

SUMMARY OF THE INVENTION An object of the present invention is to provide an external preparation for skin which shows excellent promotion of keratinization of the epidermis, promotion of synthesis of dermal collagen, antioxidant action and excellent safety.

[0007]

Means for Solving the Problems and Embodiments of the Invention In order to solve the above-mentioned problems, as a result of diligent studies, it has been found that red algae genus Halymenia, genus Meristotheca, and flucellaria (F)
urcellaria), Condracanthus Scottsbergii (Chondracanthus skit)
sbergii), Chondracanthus sandpaper (Chondracanthus sandpaper)
The present inventors have found that seaweed or an extract thereof selected from the group consisting of r) have the desired promotion of epidermal keratinization, promotion of dermal collagen synthesis, and antioxidant action, and have completed the present invention.

[0008] That is, the external preparation for skin of the present invention is a product of the genus Isonohana (Hallymenia),
otheca), Furcellar
ia) Genus, Condracanthus Scottsbergii (Ch)
ondracanthusskottsbergii),
Chondracanthus Sandperper (Chondrac)
anthus sandpaper) or a seaweed extract thereof as an active ingredient for promoting epidermal keratinization, an active ingredient for promoting dermal collagen synthesis, or an active ingredient for providing an antioxidant effect. .

[0009] The external preparation for skin of the present invention is an isonohana (Ha)
lymenia) genus, Torikanori (Meristoth)
eca) genus, Furcellaria
Genus, Kondrakansas Scottsbergii (Chond
racanthus skitsbergii, Chondracanthus sandperper (Chondracan)
thus sandpaper), a function of skin cells in which the epidermal keratinization, dermal collagen synthesis, and antioxidant substances contained in the seaweed or its extract selected from the group consisting of Improves the moisturizing, softness and elasticity of the skin by promoting
It is presumed to show a remarkable effect of preventing skin aging. In this case, by further using the humectant in combination, the physiological function of the seaweed and the humectant effect of the humectant work synergistically to provide a higher skin aging prevention effect.

Conventionally, seaweed extracts which are known to have an effect of enhancing the moisturizing property on the skin, for example, extracts of brown algae kelp and green algae such as human grass, include Isonohana genus, Tosakanori genus, and Furcelaria. The genus, Kondracanthus scotsbergii, and Kondracanthus sandperper, which are found in seaweed extracts, do not promote keratinization of the epidermis, promote the synthesis of dermal collagen, and have no antioxidant effect. It is specific to an object.

Furthermore, the safety of the seaweeds and extracts of the genus Isonohana, the genus Sasakanori, the genus Fluceraria, the chondracanthus scotsbergii, and the chondracanthus sandpaper were confirmed. Acute toxicity, skin irritation, skin sensitization No problems were observed with regard to the above points, and it was confirmed that the safety was high. Therefore, by preparing the skin external preparation of the present invention into a cosmetic cream, lotion, milky lotion or the like, it is possible to prevent skin aging and to give wrinkle-free, smooth, moist and youthful skin. As described above, the skin external preparation of the present invention has excellent epidermal keratinization promotion, dermal collagen synthesis promotion, antioxidant activity, and high safety, so that it can be used for pharmaceuticals, quasi-drugs, cosmetics, etc. It can be used for various purposes.

Hereinafter, the present invention will be described in more detail. The seaweed contained in the external preparation for skin of the present invention,
alymeniaceae) (Halym)
seaweed belonging to the genus enia),
ymenia durvilei, filigusa (Halmenia dilatata), isonohana (Halmenia floresia) and the like are used, and most preferably, tallegusa (Hallyme) is used.
niadurvilleirai). In addition, for example, Isonohana (Halmenia floresia)
The body stands upright from a plate-like applicator with a diameter of 2 to 5 mm and reaches a height of 10 to 40 cm. The color is light red, the quality is soft,
Irregular spots are seen on the surface. It is distributed in southern Kyushu and the tropical Pacific Ocean, and grows on rocks in ascending zones.

As seaweeds belonging to the genus Myristotheca (Solieriasae), there is a kind of seaweed (Meristotheca c).
oacta) and Tosakanori (Meristotheca)
papulosa) is used. In addition, for example, Tosakanori (Meristotheca papulo)
In sa), the body stands upright from the small disc-shaped applicator and suddenly spreads from a short stalk to a wide wedge-shaped flat body. It is distributed in the central and southern parts of the Pacific coast of Honshu, Kyushu and the Nansei Islands, and grows on rocks and rocks at a depth of 5 to 30 meters.

[0014] The family Susquenaceae (Furcellaria)
ceae) Furcellaria
As the seaweed belonging to the group, Furcellaria umbilicalis (Furcellaria umbilicali)
s), Furcelaria Fastighiata (Furcel)
laria fastigita), flucellaria
Lumbricaris (Furcellaria lumbr)
icalis, etc., and most preferably Furcellaria umbilicalis
umbilicalis). The body has discoid or branched appressoria, the medulla consists of a thin cell line, the skin is dense, with large cells inside and small cells outside.

[0015] Kondrakansas Scottsbergii (C
handracanthus skitsbergi
i), Condracanthus Sandpaper (Chond
racanthus sandpaper is a genus of the genus Gigartinaceae (Chinoriaceae) (Ch).
ondracanthus). Chond
The genus racanthus has heretofore been referred to as the genus Gigartina. The body is pinnately branched or foliate, and typically has a number of vegetative leaflets with papillae.

There is no particular limitation on the method for obtaining an extract from the seaweed of the genus Isonohana, the genus Tosakanori, the genus Fluceraria, the genus Kondrakansas Scottsbergii, and the kondrakansasu sandpaper contained in the external preparation for skin of the present invention. A normal extraction method is employed, and the water is extracted from seaweed using water, a hydrophilic organic solvent, a water-containing hydrophilic organic solvent, another organic solvent, and the like. Examples of the hydrophilic solvent include lower alcohols such as methanol, ethanol, and isopropanol, acetone, methyl ethyl ketone, acetonitrile, dimethyl sulfoxide, dimethyl formamide, and the like.

Among these, it is particularly preferable to perform extraction using water or a mixture of water and a lower alcohol such as methanol, ethanol and isopropanol. In this case, the ratio of water to lower alcohol is preferably 100/0 to 30/70 (V / V, volume ratio). The ratio of the original seaweed to the extraction solvent is preferably such that the original seaweed (dry matter) / solvent ratio is in the range of 1/50 to 1/2 (W / W, mass ratio).

As other extraction conditions, the extraction temperature is not particularly limited, but is preferably in the range of 5 to 80 ° C.
It is preferable to carry out with stirring for 24 hours. Extraction pH
Is not particularly limited as long as it is not inclined to extreme acidity and alkalinity.

This extract may be used as it is, or may be used as a diluent or a concentrated extract, or may be prepared as a dry powder by freeze-drying or the like, or may be prepared in a paste form. When it is prepared as a dry powder, it is preferable to use it by dissolving it in water or a lower alcohol such as methanol, ethanol, or isopropanol containing water in advance, or solubilize it in an external preparation containing water described below.

The dosage form of the external preparation for skin of the present invention is optional.
It can be formulated and used in various forms such as liniment, spray, lotion, ointment and the like.

[0021] The seaweeds and seaweed extracts of the essential components of the genus Isonohana, Tosakanori, Fluceraria, Chondracanthus scotsbergii, and Chondracanthus sandpaper can be blended at any concentration. 0.001 to 30% by mass (hereinafter simply referred to as “%”
That. ), Preferably 0.01 to 10%.

Examples of the humectant used in the present invention include polyhydric alcohols such as glycerin, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol 2000, dipropylene glycol, and amino acid derivatives such as trimethylglycine. One or more NMF components such as sodium lactate, potassium pyrrolidonecarboxylate, amino acids, sugars such as sodium hyaluronate, trehalose, heparinoid, sodium chondroitin sulfate, collagen hydrolyzate, ceramides, urea, etc. be able to. The compounding amount is usually 0.05 to 3 in various skin external preparations.
It is preferable to add 0%. If it is less than 0.05%, the effect is not exhibited, and if it is more than 30%, there is a possibility that inconveniences such as deterioration of the use feeling of the preparation may be caused.

In the skin external preparation of the present invention, in addition to the above-mentioned seaweed and its seaweed extract which are essential components, raw materials usually used for external preparations, for example, surfactants, oils, alcohols, thickeners, Preservatives, antioxidants, chelating agents, pH adjusters, fragrances, dyes, UV absorbers / scatterers, vitamins,
Water and the like can be blended.

The optional components are not limited to these. By appropriately mixing the essential components and optional components, for example, the seaweed or seaweed extract 0.01
The present invention can provide an external preparation for skin containing up to 30%, 0.05 to 30% of a humectant, 0 to 80% of an oil component as an optional component, 0 to 12% of a surfactant, a purified water balance, and a trace amount of a preservative. Specifically, it can be used as a product form such as cream, milky lotion, lotion, serum, pack, under makeup, foundation, jelly, ointment and the like.

[0025]

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

[Preparation Example 1: Production of an extract of a seaweed of the genus Isonohana] 100 g of a dried product of Halymenia durvillelai was immersed in 2 liters of water, and extracted at room temperature for 3 hours with stirring. Then, by concentrating and freeze-drying, Halmenia durvi was obtained.
32.5 g of the llaei water extract was obtained. In the same manner, an aqueous extract of a seaweed of the genus Isonohana other than Halymenia durvillaei was obtained.

[Preparation Example 2: Production of an extract of seaweed of the genus Pleurotus genus] 100 g of a dried product of Meristothea papulosa was immersed in 2 liters of water and subjected to extraction at room temperature for 3 hours while stirring. Then, by concentrating and freeze-drying, the meristostap is obtained.
28.3 g of Apulosa aqueous extract were obtained. In the same manner, Meristotheca papulosa
A water extract of a seaweed of the genus Acacia other than the above was obtained.

[Preparation Example 3: Production of extract of marine algae of the genus Furcellaria] Furcellaria umbilical
100 g of the dried is is immersed in 2 liters of water and subjected to extraction at room temperature for 3 hours with stirring. Then, by concentration and freeze-drying, Furcellari
21.5 g of a Umbilicalis water extract were obtained. Similarly, Furcellariaumb
An aqueous extract of the genus Fluceraria other than ilicalis was obtained.

[Preparation Example 4: Production of an extract of Chondracanthus scotsbergii] Chondracanthu
100 g of the dried product of sskottsbergii was immersed in 2 liters of water, and extracted at room temperature for 3 hours with stirring. Then, by concentration and freeze drying,
Chondracanthus skitsbergi
31.2 g of i water extract was obtained. In the same manner, Ch
An aqueous extract of ondracanthus sandpaper was obtained.

[Test Example 1: Involucrin expression promotion test on human epidermal keratinocytes] The above seaweed extract obtained according to the Preparation Example promotes the differentiation of normal human epidermal keratinocytes and has a therapeutic effect on keratin abnormalities. In order to prove the effect, the following test was performed on the effect on the expression of involucrin (a precursor protein of the confined envelope), which is a differentiation marker for normal human epidermal keratinocytes.

Normal human epidermal keratinocytes (manufactured by Kurabo Industries) were seeded on a 48-well collagen-coated plate (manufactured by Sumitomo Bakelite) and cultured at 37 ° C. in a 5% carbon dioxide atmosphere for 3 days. The culture supernatant was removed by suction, and a medium to which no seaweed extract was added (control) and 500 μg / ml of the above seaweed extract was added to each well, followed by further culturing for 2 days. After completion of the culture, the amount of involucrin expression was quantified by an ELISA method using an anti-involucrin antibody. Table 1 shows the results of calculating the involucrin expression level when the control was set to 1.00.

[0032]

[Table 1]

As shown in Table 1 above, it was found that the extracts of the genus Isonohana, the genus Tosakanori, the genus Fluceraria, the chondracanthus Scottsbergii, and the chondracanthus sandpaper promoted the expression of involucrin. In particular, the genus Isonohana (Halym)
In the case of the water extract of C. env. durillai), a high effect of 1.8 times was observed with respect to the control. On the other hand, in the extracts of the brown alga Kombu and the green alga Human Exa, no involucrin expression promoting effect was observed.

[Test Example 2: Test for promoting the formation of conified envelope against human epidermal keratinocytes] The seaweed extract obtained according to the Preparation Example promotes differentiation of normal human epidermal keratinocytes and has a therapeutic effect on abnormal keratinization. To prove that
The following test was conducted for the effect on the formation of the conifided envelope, a differentiation marker for normal human epidermal keratinocytes.

Normal human epidermal keratinocytes (Kurabo) are seeded on a plastic dish (Falcon).
The cells were cultured at 37 ° C. for 4 days in a 5% carbon dioxide atmosphere. The culture supernatant was removed by suction, and no addition (control) and 500
A medium to which μg / ml of the above seaweed extract was added was added to each dish, and the dishes were further cultured for 7 days. After completion of the culture, the cells were detached by trypsin treatment, and 1% SDS / 20 mM DT
After dissolving in the T solution, heat treatment was performed at 90 ° C. for 3 minutes.
After the heat treatment, the number of insolubilized cells was counted, and the number was regarded as the number of conifiable envelopes. Table 2 shows the results.

[0036]

[Table 2]

As is clear from the results shown in Table 2 above,
Extracts of the genus Isonohana, genus Tosakanori, genus Fluceraria, Condracanthus Scottsbergii, and Condracanthus sandpaper were found to promote conifided envelope formation. In particular, Halymenia durvillae of the genus Isonohana
i), Condracanthus Sandpaper (Chond
In the case of the water extract of Racanthus sandpaper, a high effect of a confined envelope formation rate of 30% or more was observed.

[Test Example 3: Test for promoting collagen synthesis on human skin-derived fibroblasts] The following test was conducted on the effect of the seaweed extract obtained according to the Preparation Example on the promotion of collagen synthesis on human skin-derived fibroblasts. .

Human skin-derived fibroblasts (manufactured by Kurabo Co., Ltd.) were placed on a 24-well cell culture plate (manufactured by Sumitomo Bakelite).
Was inoculated to 25% confluence, and cultured at 37 ° C. in a 5% carbon dioxide gas atmosphere in a DMEM medium containing 10% fetal bovine serum until confluence. After adding an appropriate amount of the sample, it was cultured under the same conditions for 18 hours. Type I collagen contained in the culture supernatant was quantified by ELISA. 100 μl of the culture supernatant was added to the ELISA plate and stored at room temperature for 18 hours. 0.05% Tween
After washing with PBS containing n-20 (PBS-T), the cells were blocked with 1% skim milk / PBS-T for 2 hours. The cells were treated with an anti-human type I collagen antibody and a peroxidase-labeled anti-rat IgG antibody, and the color was developed using a peroxidase color development kit. The amount of type I collagen contained in the culture supernatant was determined from the absorbance at 450 nm. The amount of type I collagen was 120% or more with respect to the control.
0% or more and less than 120% were represented by O, and less than 100% were represented by X. Table 3 shows the results.

[0040]

[Table 3]

As is clear from the results shown in Table 3 above,
Extracts of the genus Isonohana, genus Tosakanori, genus Fluceraria, Condracanthus Scottsbergii, and Condracanthus sandpaper were found to promote collagen synthesis. In particular, Filigusa (Halmenia)
dilatata), kikutosaka (Meristoth)
ecacacta), Condracanthus Scottsbergii (Chondracanthus skits)
bergii), the amount of type I collagen is 1
A high effect of 20% or more was recognized.

[Test Example 4: Singlet Oxygen Scavenging Ability Test] Using the seaweed extract obtained according to the Preparation Example, the following test was carried out for the ability to scavenge singlet oxygen that damages living tissues.

Singlet oxygen was generated by irradiating Rose Bengal (manufactured by Wako Pure Chemical Industries) with a fluorescent lamp, and the singlet oxygen scavenging ability was measured using the degree of oxidation of squalene as an index. A solution was prepared by adding an appropriate amount of a sample and methanol to 3 mM squalene and 25 μM rose bengal. Control only received methanol. 4 ℃
For 18 hours. A blank with an irradiation time of 0 hours was used as a blank. The resulting squalene peroxide was quantified by the TBA method. 1,1,3,3-tetraethoxypropane (manufactured by Wako Pure Chemical Industries, Ltd.) was used as a standard substance. Add 1 ml of TBA reagent (0.375% thiobarbitol acid,
2 ml of 15% trichloroacetic acid, 0.04% butylhydroxytoluene, 2% ethanol and 0.25N hydrochloric acid) were added, and after stirring, the mixture was heated on a boiling water bath for 1 hour. After cooling with ice and cooling to room temperature, the mixture was extracted with butanol, and the absorbance at 535 nm was measured using a blank as a control. The degree of the singlet oxygen scavenging ability is represented by a relative value when the TBA value of the control is taken as 100, and 90% or more is represented by ◎, 60% or more is 90% or more.
The percentage is shown as ○, the percentage of 30% or more as 60% as Δ, and the percentage of 30% as ×. Table 4 shows the results.

[0044]

[Table 4]

As is evident from the results in Table 4, the extracts of the genus Isonohana, the genus Tosakanori, the genus Fluceraria, the chondracanthus Scottsbergii, and the chondracanthus sandpaper were found to have high singlet oxygen scavenging ability. did.

[Test Example 5: Skin photoaging test] Two hairless mice per group (hos: HR-1, 9 to 10 weeks old,
Female) Apply 50mJ once a day to the back skin with ultraviolet light (UV-B)
/ Day · cm ^2, and then 100 μl of the test solutions shown in Table 5 (Comparative Examples 1 to 5, Examples 1 to 10)
Was applied uniformly, and this was performed 5 days a week for 5 weeks. At the time of ultraviolet irradiation, the test substance remaining on the skin was thoroughly wiped with a 30% ethanol solution before irradiation. When the ultraviolet irradiation and application for 5 weeks were completed, the water content of the stratum corneum was measured using Corneometer (Coura).
ge & Khazaka), and the amount of transepidermal water loss (hereinafter abbreviated as TEWL) is determined by TEWAMETER TM2.
10 (manufactured by Courage & Khazaka) and skin elasticity with Cutometer SEM575 (Cou
(Rage & Khazaka).

The three indices evaluated were compared with the values of the control group (Comparative Example 1) of each index. When the values were hardly changed, x was given, Δ was slightly improved, o was improved, The case of improvement was indicated by ◎. Table 5 shows the results.

[0048]

[Table 5]

As is evident from the results in Table 5, each seaweed extract (Examples 1 to 5) except for human grass (Comparative Example 2) shows a high protective effect against skin photoaging and is used in combination with a moisturizing agent. In Examples 6 to 10, it was found that a remarkable effect was exhibited.

Hereinafter, Formulation Examples in which the skin external preparation of the present invention is blended are shown. The following examples all showed excellent effects such as skin roughness improvement effect, keratin improvement effect, and beautiful skin effect (smoothness, moist feeling, tension, gloss, etc.), and good safety.

[0051]

[Table 6]

[0052]

[Table 7]

[0053]

[Table 8]

[0054]

[Table 9]

[0055]

[Table 10]

[0056]

[Table 11]

[0057]

[Table 12]

[0058]

[Table 13]

[0059]

[Table 14]

[0060]

[Table 15]

[0061]

[Table 16]

[0062]

According to the present invention, the activation of skin cells and the prevention of skin aging are promoted by the promotion of keratinization of the epidermis, the promotion of dermis collagen synthesis, and the antioxidant action, thereby preventing the occurrence of wrinkles and making the skin smooth and moist. With the effect of giving youthful skin
A highly safe skin external preparation is provided.

The active ingredient of the external preparation for skin of the present invention comprises:
Since it is extracted from seaweeds used for food etc. since ancient times, it is extremely safe for the human body and has excellent epidermal keratinization promotion, dermal collagen synthesis promotion, and antioxidant action, It can be used for various purposes such as quasi-drugs and cosmetics.

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Claims (4)

[Claims] 1. a genus of Halymenia,
Genus Meristoteca, Furcellaria, Chondracanthus Scottsbergii (Chondracanthus)
skitsbergii), Chondracanthus sandpaper (Chondracanthus sandp)
A skin external preparation characterized by containing one or more seaweeds or extracts thereof selected from the group consisting of aper) as an active ingredient for promoting epidermal keratinization. 2. A genus of Halymenia,
Genus Meristoteca, Furcellaria, Chondracanthus Scottsbergii (Chondracanthus)
skitsbergii), Chondracanthus sandpaper (Chondracanthus sandp)
a) a skin algae or an extract thereof selected from the group consisting of aper) as an active ingredient for promoting dermal collagen synthesis. 3. A genus of Halymenia,
Genus Meristoteca, Furcellaria, Chondracanthus Scottsbergii (Chondracanthus)
skitsbergii), Chondracanthus sandpaper (Chondracanthus sandp)
A skin external preparation characterized by containing one or more of a seaweed or an extract thereof selected from the group consisting of aper) as an active ingredient having an antioxidant effect. 4. The external preparation for skin according to claim 1, further comprising a humectant.