JPH06256137A - Beautifying dermatic external preparation - Google Patents

Abstract

PURPOSE:To provide an external preparation effective for eliminating pigmentation such as spots, also of extremely high safety. CONSTITUTION:The dermatic external preparation containing 0.00001-20 (pref. 0.0001-10)wt.% of ferulic acid compound (or a glycoside thereof) of the formula (R is H or pentose or hexose residue) which can be obtained by conifer blasting. Application of this external preparation suppresses the activity of tyrosinase, an oxidase, closely involved in melanization in the epidermal pigment cells and the hair, reducing the production of melanin, thus having improving effect for skin whitening and pigment elimination. The compound of the formula is most preferably nonglycosidated ferulic acid or ferulic DELTA-D-glucose in terms of beautifying effect, industrial convenience and safety etc.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin external preparation which contains ferulic acid or a glycoside thereof as an active ingredient and is excellent in skin whitening effect and safety.

[0002]

BACKGROUND OF THE INVENTION There are many unclear points about the mechanism of skin pigmentation such as stains and freckles, but it is generally caused by exposure to ultraviolet rays, abnormal hormone secretion, and abnormal melanin metabolism. It is believed that the production of melanin pigment in the epidermis is accelerated and deposited in the skin.

Conventionally, various substances have been applied to reduce or prevent skin pigmentation. Hydroquinone is known as one having a strong bleaching action, but there is a problem in terms of safety such that the action on the skin is too strong and permanent dye escape may occur. In recent years, kojic acid, arbutin, etc. have been developed and applied as highly safe skin whitening agents, but their effects are slow, and there is a problem that the effects are difficult to obtain unless they are used for a long period of time. A highly effective treatment method is required.

[0004]

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a new skin external preparation which is safer and has a high skin whitening effect.

[0005]

That is, the present invention comprises a highly safe and highly effective skin whitening agent characterized by containing ferulic acid represented by the following formula (1) or a glycoside thereof. Is.

[0006]

[Chemical 2] [In the formula, R represents hydrogen or a residue of 6 monosaccharide or 5 monosaccharide].

Ferulic acid in which R is H in the above formula (1) is a substance that can be obtained at a low cost as a decomposed product of lignin which is a natural organic compound contained in almost all plant tissues such as wood. Although many attempts have been made to use the lignin, for example, it is used as a synthetic raw material, vanillin, produced at low cost by oxidation of lignin, or used as a soil conditioner. However, since these are the typical usage methods and others are not on the industrial profit base, although there are many in the natural world, their usage is not sufficient and most of them are burned. is the current situation. However, the present inventors have surprisingly found that ferulic acid and its glycosides obtained by bombarding coniferous trees have the property of inhibiting the activity of the oxidative enzyme tyrosinase that produces melanin pigment, The present invention has been completed.

[0008] It is understood that skin pigmentation is a phenomenon in which melanin pigment production in epidermal pigment cells, which has been promoted by stimulation with ultraviolet rays, inflammation, etc., remains unstimulated and enhanced. Tyrosine oxidase (tyrosinase) in pigment cells plays a major role in the production of melanin pigment.

By applying a skin external preparation containing ferulic acid and its glycoside as an active ingredient, the activity of the oxidative enzyme tyrosinase, which is greatly involved in the formation of melanin in epidermal pigment cell hair, is suppressed and the production of melanin pigment is suppressed. It is effective in reducing skin whitening and improving pigmentation.

In the present invention, ferulic acid or a glycoside of ferulic acid represented by the above general formula (1) is used.
In the formula, R is a hydrogen group or a residue of a hexasaccharide such as D-glucose, D-galactose, D-mannose, D-talose, D-fructose, L-galactose, or D-.
It shows residues of 5 monosaccharides such as arabinose, D-xylose, D-ribose, D-ribulose, L-arabinose, L-xylose, L-ribose and L-ribulose, but has a whitening effect, industrial convenience, and stability. From the viewpoint of properties, ferulic acid which is not glycosylated or β-D-glucose of ferulic acid to which β-bond of D-glucose is most preferable.

The amount of ferulic acid and its glycosides mixed depends on the dosage form and the like, and is not particularly limited, but is usually 0.00001 to 20% by weight, preferably 0.000.
The amount is 1 to 10% by weight, and if it is less than 0.0001% by weight, it is difficult to obtain sufficient effects of whitening the skin and improving pigmentation.

The external preparation for skin of the present invention is suitable for hair cosmetics such as hair nick, hair treatment, hair cream, hair shampoo, hair rinse, etc., and the dosage form is any externally applicable dosage form. Well, its ingredients are also various ingredients that are commonly used in cosmetics, quasi-drugs and pharmaceuticals, for example, solvents such as alcohol and solubilizers, surfactants, humectants, fragrances, colorants,
Preservatives, viscosity modifiers and the like can be added as appropriate.

[0013]

The effects and safety of the thus obtained external preparation for skin of the present invention are as follows.

Test Example Test Example 1: Tyrosinase activity inhibition test (1) Preparation of crude tyrosinase enzyme solution B16 melanoma cells were mixed with 10% FCS and pen.
icillin, streptomycin, amph
Dul including OtericinB (Funzizon)
becco's modified eggs m
In an edium, culture was performed (95% air, 5% CO ₂ ) under the condition of 37 ° C using a culture dish (φ9 cm) or a culture flask (75 cm ² ). The cells grown by culturing for 2 to 3 days were treated with Trypsin for 3 minutes to be suspended, and centrifuged (450 xg, 3 minutes) to collect the cells. The obtained cells were washed 3 times with a phosphate buffer (pH 6.8) containing 10 mM physiological saline, the number of cells was counted, and then 0.1 M containing 0.1% triton X-100 was added.
It was suspended in a phosphate buffer (pH 6.8). The suspension was sonicated (15 sec × 3 times) while cooling with ice, and centrifuged (11,000 × g, 20 minutes, 4 ° C.) to collect the supernatant. The resulting supernatant was used as a crude tyrosinase enzyme solution.

(2) Action of ferulic acid and its glycoside on the activity of tyrosinase The activity of tyrosinase was determined according to the method of Akiu et al. That is, 0.5 ml of crude tyrosinase enzyme solution and 50 mM phosphate buffer solution of ferulic acid and its glycoside (pH 6.8,
Hereinafter, this is abbreviated as a buffer) 0.1 ml was mixed, 0.9 ml of the buffer was further added, and the mixture was heated at 37 ° C. for 3 minutes.
0.5 ml of a buffer solution containing 0.067% L-dopa was added, and the change in absorbance at 475 nm at 37 ° C. was measured over time. The tyrosinase activity was calculated from the obtained initial rate of change in absorbance, and the inhibition rate was calculated from the following formula. In addition,
Ferulic acid and its glycosides were buffered with 0.1, 1.
0, and 10 mg / ml (final concentration 0.005, 0.0
5, 0.5 mg / ml) and centrifuged (11,0
(00 × g, 20 minutes, 4 ° C.) was added to the reaction system. In the formula, ferulic acid and its glycoside are abbreviated as test agents.

[0016]

[Equation 1] The results are shown in Table 1. As a result, ferulic acid and its glycosides, which are the active ingredients of the hair cosmetic composition of the present invention, inhibit the activity of tyrosinase, an enzyme that produces melanin pigment, and have an effect on skin whitening. I understand.

[0017]

[Table 1]

Test Example 2: Skin sensitization test (patch test) Reagent: 10% ferulic acid and its glycoside aqueous solution Method of implementation: 20 males aged 20-60 years, 2 females
A fin chamber filter paper, in which a sample and a control solution (physiological saline) were respectively immersed in the flexed side of the upper arm of a subject consisting of 0 persons, was placed in the chamber portion of the fin chamber and affixed to the closed patch test. The application time was 24 hours, the fin chamber was removed after 24 hours, and 30 minutes after sample removal, and 3 hours of 24 hours and 48 hours.
Judgment was performed once. Criteria:-: No reaction ±: Slight erythema +: Clear erythema ++: Erythema and swelling or papules ++: Blisters are observed. As shown in Table 2, ferulic acid and the active ingredients of the hair cosmetic composition of the present invention It was revealed that the glycoside has a very low possibility of inducing irritation reaction and allergic reaction and is highly safe.

[0019]

[Table 2]

[0020]

EXAMPLES Examples of the present invention will be shown below. Incidentally, these examples do not limit the present invention at all.

Example 1 <Hear tonic> A hair tonic was prepared by mixing and agitating each component in the following composition by a conventional liquid mixer with a metal blade. Ferulic acid 0.5 g Polyoxyethylene (9) lauryl ether 1.0 g 1,3 butylene glycol 5.0 g Ethanol 50.0 g Perfume 0.3 g Purified water Suitable amount Total 100.0 g

Example 2 <Hair Treatment> Each component having the following composition was mixed and stirred by a liquid mixer with a metal blade according to a conventional method to produce a hair treatment. Ferulic acid β-D-glucose 1.0 g Polyoxyethylene (10) behenyl ether 5.0 g Glycerin monostearate 6.0 g Isopropyl myristate 5.0 g Stearic acid 5.0 g Liquid paraffin 5.0 g Lanolin alcohol 3.0 g 1 , 3 Butylene glycol 5.0 g Triethanolamine 1.0 g Methyl parapen 0.1 g Ethyl parapen 0.1 g Perfume 0.3 g Purified water Suitable amount Total 100.0 g

Example 3 <Hair Cream> A hair cream was produced by mixing and emulsifying each component in the following composition by a vacuum emulsifying machine according to a conventional method. Ferulic acid 1.0 g Liquid paraffin 30.0 g Dehydrated lanolin 3.0 g Beeswax 2.0 g Cetanol 3.0 g Glycerin 5.0 g Polyoxyethylene (10) cetyl ether 3.0 g Sorbitan monostearate 0.1 g Methyl parapen 0.1 g Ethyl Parapen 0.1g Perfume 0.5g Purified water Suitable amount Total 100.0g

Example 4 <Hair shampoo> A hair shampoo was prepared by mixing and agitating each component in the following composition by a liquid mixer with a metal blade according to a conventional method. Ferulic acid β-D-glucose 0.5 g Lauryl sulfate triethanolamine 20.0 g Sodium lauryl sulfate 5.0 g Magnesium stearate 5.0 g Lanolin 1.0 g 1,3 Butylene glycol 5.0 g Cetyl alcohol 2.0 g Polyvinyl alcohol 1 0.0 g Fragrance 0.5 g Purified water Suitable amount Total 100.0 g

Example 5 <Hair Rinse> The following components were mixed and stirred in a liquid mixer with a metal blade according to a conventional method to produce a hair rinse. Ferulic acid 0.5 g Polyoxyethylene (2) oleyl ether 7.0 g Distearyldimethylammonium chloride 3.0 g Propylene glycol 3.0 g Methyl parapen 0.1 g Ethyl parapen 0.1 g Perfume 0.3 g Purified water Total amount 100.0 g

[0026]

Industrial Applicability The whitening skin external preparation of the present invention is effective in whitening skin pigmentation such as spots, and is extremely safe.

 ─────────────────────────────────────────────────── ─── Continued Front Page (72) Masataka Funayama 14-5 Shimokita Town, Neyagawa City, Osaka Prefecture Kurashiki Spinning Co., Ltd. Technical Research Institute (72) Hirokuni Arakawa 14-5 Shimokita Town, Neyagawa City, Osaka Spinner Kurashiki Technical Research Institute Co., Ltd.

Claims (1)

[Claims] 1. An external preparation for skin comprising ferulic acid represented by the following formula (1) or a glycoside thereof. [Chemical 1] [In the formula, R represents hydrogen or a residue of 6 monosaccharide or 5 monosaccharide]