JP5049638B2 - Topical skin preparation - Google Patents

Description

  The present invention relates to an external preparation for skin, in which the effectiveness of a preparation containing a melanin production inhibitor comprising rhododendrol and its derivatives is enhanced and the feeling is remarkably improved.

  Conventionally, as a component for preventing or improving pigmentation such as skin stains and freckles caused by excessive melanin production in epidermal pigment cells and excessive deposition on the epidermis, L-ascorbic acid and its derivatives, arbutin and the like Hydroquinone derivatives and pyrones such as kojic acid are used.

  These substances are known as substances having a whitening effect such as suppression of melanin production and lightening of the produced melanin. However, these substances are insufficient to prevent inflammation that causes pigmentation and prevent metabolism from staying inside the skin by activating metabolism.

  Further, rhododendrol and its derivatives have been proposed as components for improving pigmentation caused by exposure to ultraviolet rays (see Patent Documents 1 to 3), and the effect of promoting proliferation of epidermal cells is also known (Patent Document). 4).

  However, the causes of stains, freckles, etc. are complex, and even when rhododendrol and its derivatives are blended alone, the effect is often not fully demonstrated, and solutions are made by increasing the blending amount etc. However, there are cases where problems arise in terms of cost, stability in the formulation, and feel, and improvements have been demanded.

  On the other hand, ethyl glucoside has a keratinocyte keratinization promoting effect and has been reported as a component for preventing and improving rough skin (see Patent Documents 5 to 6 and Non-Patent Document 1).

  Mucopolysaccharide is a natural skin moisturizing factor, and it is known that hyaluronic acid and glycerin in particular increase the moisturizing effect synergistically, and the continuous improvement in flexibility due to increased moisture in the stratum corneum ( Non-patent document 2).

However, mucopolysaccharide has a unique stickiness when applied to the skin, and has the property of further enhancing its drawbacks when used in combination with glycerin and other polyhydric alcohols.
Japanese Patent No. 3340928 Japanese Patent No. 3340935 Japanese Patent No. 3455406 JP 2004-196818 A JP-A-10-306010 JP-A-2005-314310 37th SCCJ Research Discussion Meeting, Abstracts, p43-45, published on November 16, 1995 Fragrance Journal Special Issue No. 9, p137-139, (1988)

  Then, an object of this invention is to provide the skin external preparation with the sufficient feeling of use in which the effect of rhododendrol and its derivative is fully exhibited.

  As a result of intensive studies to solve the above problems, the present inventors have synergistically improved the whitening effect by using rhododendrol and its derivatives in combination with ethyl glucoside known as a rough skin improving component. And after application | coating which is a fault of the mucopolysaccharide mix | blended in order to improve a whitening effect further, the stickiness at the time of drying was suppressed and it discovered that a formulation with high touch evaluation was obtained, and came to complete this invention.

  The skin external preparation of the present invention remarkably improves the effect of rhododendrol as a whitening agent, further has an effect of preventing rough skin, and is excellent in use feeling.

  The configuration of the present invention will be described in detail below.

  Rhododendrol [4- (p-hydroxyphenyl) -2-butanol] used in the present invention is a known compound and is known to be contained in Acer nikoence Maxim.

  In addition, the rhododendrol and acylated rhododendrol used in the present invention have optical isomers, but the (+) isomer, the (−) isomer alone, or a mixture thereof [denoted as (±), JP-A-3-251548] can also be used.

  The acyl group having 2 to 20 carbon atoms defined in the formula (1) in the present invention is not particularly limited as long as it is generally used, but it is linear from the viewpoint of stability and ease of synthesis. Saturated acyl groups are preferred. Examples of the acylated rhododendrol used in the present invention include (+) isomer, (−) isomer, and (±) such as hexanoyl rhododendrol and acetyl rhododendrol.

  As a method for obtaining the glycoside of the present invention, a method already known as a method for synthesizing arbutin (USP No. 3121385) can be used. For example, after condensing rhododendrol and acetylated sugar in an organic solvent such as toluene using boron trifluoride, phosphorus oxychloride or the like as a catalyst, the glucoside of the present invention is eliminated by eliminating the acetyl group in the presence of alkali. The body can be easily obtained as white powder crystals. It can also be obtained by reducing raspberry ketone glycosides. It is also possible to isolate from natural products. The glycosides of the present invention have optical isomers, but (+) isomers, (−) isomers alone or a mixture (±) thereof can also be used.

  The sugar residue used in the present invention is a reducing monosaccharide or disaccharide, specifically, monosaccharides such as glucose, galactose, xylose, mannose, N-acetylglucosamine, maltose, cellobiose, gentibiose and the like. Sugars can be mentioned. In the glycoside of the present invention, there are isomers having an α bond and a β bond, and these can be used alone or a mixture thereof.

  Specific glycosides used in the present invention include rhododendrol-D-glucoside (α and β forms), rhododendrol-D-galactoside (α and β forms), rhododendrol-D-xyloside (α And (+) form, (-) form, and (±) such as rhododendrol-D-maltoside (α and β form).

  Although there is no restriction | limiting in particular as a compounding quantity of the rhododendrol and its derivative mix | blended with the skin external preparation of this invention, when considering the effect on skin, 0.01 mass% or more is preferable, and it is effective as a melanin production inhibitor. In order to exhibit strongly, it is preferable to mix | blend 0.5 mass% or more. The upper limit of blending is preferably 5.0% by mass due to the properties as a skin external preparation.

  The ethyl glucoside used in the present invention is known as a fermentation product contained in a fermentation product such as sake, but it does not affect the present invention with respect to its origin, and may be a synthetic product. It is desirable to use an α isomer or a mixture of structural isomers, which have a structural isomer and have been confirmed to have an effect of improving rough skin.

  Although there is no restriction | limiting in particular as a compounding quantity of the ethyl glucoside mix | blended with the skin external preparation of this invention, 0.01-1.0 mass% is preferable.

  Furthermore, it is preferable to add mucopolysaccharide as a moisturizing agent to the skin external preparation of the present invention in order to enhance the whitening effect.

  The mucopolysaccharide used in the present invention is hyaluronic acid or a salt thereof, a hyaluronic acid derivative, chondroitin-4-sulfate, chondroitin-6-sulfate, keratan sulfate, heparin, chitin, chitosan, and salts thereof, preferably hyaluron. Sodium acid and dimethylsilanol hyaluronate.

  Hyaluronic acid and a salt or derivative thereof used in the present invention include a low molecular type and a high molecular type, and are selected according to required formulation characteristics. Specific examples thereof include hyaluronic acid FCH-SU, hyaluronic acid FCH (FCH-120) [manufactured by Kibun Food Chemical Co., Ltd.], DSHC (N) [manufactured by EXSYMOL], and the like.

  The blending amount of the mucopolysaccharide used in the present invention is preferably 0.001% by mass or more, and the upper limit of blending is not particularly limited, but when blended in an extremely large amount, the effect of the present invention is not impaired, but the skin From the above, the twist and the crispness peculiar to the polymer are generated, so the amount is preferably 1.0% by mass or less.

  Furthermore, in the external preparation for skin of the present invention, within the range not impairing the effects of the present invention, in addition to the above essential components, other ingredients usually blended in pharmaceuticals, quasi-drugs, cosmetics, etc., such as oils and moisturizers. , Surfactants, thickeners, preservatives, pH adjusters, water, alcohols, drugs, ultraviolet absorbers, ultraviolet scattering agents, dyes, fragrances, and the like can be appropriately blended as necessary.

  Moreover, it can be set as arbitrary dosage forms, such as ointments, lotions, emulsions, creams, and packs.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example and a comparative example, this invention is not limited by this.

  In addition, (1) skin color brightness recovery test method, (2) measurement method for rough skin improvement effect, and (3) sensory test method for evaluating the effect of the external preparation for skin of the present invention are as follows.

(1) Skin color brightness recovery test method 20 subjects' back skin was irradiated with UV rays in the UV-B region twice as much as the minimum erythema amount, and the sample application site and non-application site were set, and the standard brightness of each skin ( V0 value, V0 ′ value) were measured. Subsequently, after the sample was applied to the application site twice a day for 15 weeks continuously, the lightness of the skin at the application site and non-application site after 3, 6, 9, 12, 15 weeks (Vn value, Vn ′ value) The skin color recovery was evaluated according to the following criteria. The lightness of the skin (Munsell color system V value) was calculated from X, Y, and Z values obtained by measurement with a high-speed spectral colorimeter. Moreover, evaluation was shown with the average value of the evaluation score after 3 weeks about 20 test subjects.

Evaluation criteria Criteria
Sample whose skin lightness recovery value for each week satisfies the following formula 5 ΔV−ΔV ′ ≧ 0.12
4 0.12> ΔV−ΔV ′ ≧ 0.08
3 0.08> ΔV−ΔV ′ ≧ 0.04
2 0.04> ΔV−ΔV ′ ≧ 0
1 0> ΔV−ΔV ′

ΔV ... Recovery value of the application site (Vn-V0)
ΔV′—Recovery value of non-application area (Vn′−V0 ′)

(2) Measurement test method of rough skin improvement effect The effect of continuous application was examined for 20 middle-aged subjects having rough skin on the lower leg for 4 weeks. About 1 g of a sample was applied to the subject's left lower leg test site twice a day (morning and evening), and the skin condition before and after the start of the test was determined according to the following criteria. The lower right leg was used as a control with no sample applied. The judgment results of the test site before and after the test and the control site are compared, and when the skin dryness is improved by two or more levels (for example, + → −, ++ → ±) is “effective”, and when the level is improved by 1 level, “Slightly effective” and “invalid” when there was no change. The test result was shown by the number of subjects who became “effective” and “slightly effective”.

Judgment criteria for skin dryness-: Normal ±: Light dryness, no desquamation +: Dryness, mild desquamation ++: Dryness, moderate desquamation +++: Significant dryness, desquamation

(3) Sensory test method The characteristics of the samples after 20 subjects continuously used the samples for one month were evaluated. Evaluation was based on questionnaire items of wettability, whitening effect, elasticity, and stickiness, “Moisturized skin”, “I felt whitening effect”, “Tightness on skin”, “After application” “There is no sticky feeling”.

Examples 1-4, Comparative Examples 1-3
One kind selected from rhododendrol and derivatives thereof and one kind of ethyl glucoside and mucopolysaccharide were blended in the composition shown in Table 1, and a cosmetic liquid was prepared by the following preparation method. The above test was carried out for each, and the results are also shown in Table 1.

Preparation Method After the alcohol part of (A) and the aqueous phase part of (B) were each uniformly dissolved, the aqueous phase was added to the alcohol part to solubilize it to obtain a cosmetic liquid.

  A topical skin preparation was prepared by a conventional method according to the following formulation.

Application example 1 (lotion)
Raw material component amount (% by mass)
--------------------------------------
Dipropylene glycol 12.0
Concentrated glycerin 5.0
Decaglycerin monolaurate 0.5
Rhododendrol 1.5
Ethyl glucoside (α form) 0.02
Sodium hyaluronate (* 1) 0.05
Citric acid 0.01
Sodium citrate 0.09
Phenoxyethanol 0.3
Dipotassium glycyrrhizinate 0.1
Licorice extract (* 2) 0.1
Yeast extract (* 3) 0.1
Chimpi extract (* 4) 0.05
Juzudama extract (* 5) 0.05
Thai Saw Extract (* 6) 0.05
Honeysuckle extract (* 7) 0.05
Tonin extract (* 8) 0.05
Gardenia extract (* 9) 0.05
Yukinoshita extract (* 10) 0.05
Tea seed extract (* 11) 0.01
Camellia extract (* 12) 0.01
Orchid extract (* 13) 0.05
Ghetto leaf extract (* 14) 0.05
Purified water residue * 1; Hyaluronic acid FCH-SU (manufactured by Kibun Food Chemical Co., Ltd.)
* 2; Licorice extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.)
* 3: East Liquid ZB (Ichimaru Falcos)
* 4; Chimp extract BG (Maruzen Pharmaceutical Co., Ltd.)
* 5: Yokuinin extract BG-S (manufactured by Maruzen Pharmaceutical Co., Ltd.)
* 6: Titanium extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.)
* 7: Falco Rex Honeysuckle SB (manufactured by Ichimaru Falcos)
* 8: Falco Rex Tonin B (made by Ichimaru Falcos)
* 9: Falco Rex Gardenia B (Ichimaru Falcos)
* 10: Yukinoshita extract (manufactured by Ichimaru Falcos)
* 11: Tea extract (Maruzen Pharmaceutical Co., Ltd.)
* 12: Camellia seed extract (Maruzen Pharmaceutical Co., Ltd.)
* 13: Falco Rex Run (made by Ichimaru Falcos)
* 14: Moon peach extract BG (Maruzen Pharmaceutical Co., Ltd.)

Application example 2 (lotion)
Raw material component amount (% by mass)
--------------------------------------
Ethanol 5.0
1,3-butylene glycol 4.0
Concentrated glycerin 2.0
Diglycerin 1.0
Chondroitin-4-sulfate sodium 0.5
Polyoxyethylene hydrogenated castor oil (60 EO) 0.3
Polyoxyethylene sorbitan monolaurate (20E.O.) 1.0
Rhodendrol-D-glucoside 2.0
Ethyl glucoside (mixture of isomers) 0.05
Potassium dihydrogen phosphate 0.07
Sodium monohydrogen phosphate 0.03
Dehydrodicreole 0.01
Methylparaben 0.1
Glycine 0.01
L-alanine 0.01
L-proline 0.01
L-serine 0.01
N-methyl-L-serine 0.1
L-carnitine chloride 0.1
Mixed fruit extract (* 15) 0.1
Apricot juice (* 16) 0.1
Wheat germ extract (* 17) 0.1
Rooibos extract (* 18) 0.1
Melia azadiracta leaf extract (* 19) 0.1
Purified water balance * 15; Multi-fruit BSC (Arch Personal Care Products)
* 16: Apricot extract K (Esperis)
* 17: Clariskin (manufactured by Silab)
* 18; Falco Rex Rooibos B (N) (Ichimaru Falcos)
* 19 Neem Leaf Liquid B (Ichimaru Falcos)

Application example 3 (milky lotion)
Raw material component amount (% by mass)
--------------------------------------
Ethanol 10.0
Polyoxyethylene oleyl ether (2E.O.) 0.2
Polyoxyethylene cetyl ether (2E.O.) 0.1
Polyoxyethylene hydrogenated castor oil (60 EO) 0.3
Methylphenylpolysiloxane 1.0
Glyceryl tri-2-ethylhexanoate 1.0
Dipropylene glycol 1.0
Concentrated glycerin 2.0
Hexanoyl rhododendrol 1.5
Ethyl glucoside (α form) 0.05
Sodium hyaluronate (* 1) 0.1
Dimethylsilanol hyaluronate 0.05
Carboxyvinyl polymer 0.3
Potassium hydroxide 0.1
Phenoxyethanol 0.1
Acerola seed extract (* 20) 0.1
Camcom fruit extract (* 21) 0.1
Mevalonolactone 0.1
Flavin adenine dinucleotide disodium (* 22) 0.01
Nicotinamide 0.1
Pyridoxine hydrochloride 0.1
Pyridoxine tri-2-hexyldecanoate (* 23) 0.01
Ascorbic acid disodium sulfate (* 24) 0.1
Tocopherol acetate (* 25) 0.1
β-carotene (* 26) 0.001
Fragrance 0.05
Purified water residue * 20; Nichirei Acerola Seed Extract B30 (manufactured by Nichirei)
* 21: Nichirei Cam Come Extract B30 (manufactured by Nichirei)
* 22; FAD (manufactured by Kyowa Hakko)
* 23; NIKKOL VB6-IP (Nikko Chemicals)
* 24: VC-SS (manufactured by Nippon Surfactant)
* 25; dl-α-tocopherol acetate (manufactured by Eisai Co., Ltd.)
* 26: β-carotene (Roche)

Application example 4 (milky lotion)
Raw material component amount (% by mass)
--------------------------------------
Hydrogenated soybean phospholipid 1.0
Cholesterol 0.5
Squalane 2.0
Macadamia nut oil fatty acid phytosteryl 0.5
Ceramide 2 (* 27) 0.5
1,3-butylene glycol 3.0
Concentrated glycerin 3.0
Polyglycerin 1.0
Squalane 1.0
Rhododendrol 1.0
Ethyl glucoside (mixture of isomers) 0.05
Sodium hyaluronate (* 28) 0.1
Acrylic acid methacrylate alkyl copolymer 0.05
Xanthan gum 0.05
Sodium hydroxide 0.02
Phenoxyethanol 0.3
Dipotassium glycyrrhizinate 0.1
Licorice extract (* 2) 0.1
Yeast extract (* 3) 0.1
Chimpi extract (* 4) 0.05
Juzudama extract (* 5) 0.05
Thai Saw Extract (* 6) 0.05
Honeysuckle extract (* 7) 0.05
Tonin extract (* 8) 0.05
Gardenia extract (* 9) 0.05
Yukinoshita extract (* 10) 0.05
Tea seed extract (* 11) 0.01
Camellia extract (* 12) 0.01
Orchid extract (* 13) 0.05
Ghetto leaf extract (* 14) 0.05
Purified water residual amount * 27; Ceramide TIC-001 (manufactured by Takasago International Corporation)
* 28: Hyaluronic acid FCH (FCH-120) (manufactured by Kibun Food Chemical Co., Ltd.)

Application example 5 (skin cream)
Raw material component amount (% by mass)
--------------------------------------
Cetanol 5.0
Lipophilic glyceryl monostearate 1.0
Polyoxyethylene cetyl ether (2E.O.) 0.1
Sucrose fatty acid ester (* 29) 0.5
Vegetable squalane 1.0
Refined jojoba oil 1.0
Refined macadamia oil 1.0
Hydrogenated polyisobutene 1.0
Ceramide 3 (* 30) 0.1
Tocopherol nicotinate 0.1
Olive oil (* 31) 0.1
Avocado oil (* 32) 0.1
Grape seed oil (* 33) 0.1
Concentrated glycerin 5.0
Rhododendrol 1.5
Ethyl glucoside (isomer mixture) 0.1
Sodium hyaluronate (* 28) 0.3
Chondroitin-4-sulfate sodium 0.3
Phenoxyethanol 0.3
Chlorphenesin 0.1
Perfume 0.02
Purified water remaining amount * 29; Sugar wax A-10E (Daiichi Kogyo Seiyaku Co., Ltd.)
* 30; Ceramide IIIA (manufactured by Cosmo Farm)
* 31; Cropure OL (manufactured by Croda Japan)
* 32; Crop Pure Avocado (Crowda Japan)
* 33; Grape seed oil (Nikko Chemicals)

Application Example 6 (Cosmetic liquid)
Raw material component amount (% by mass)
--------------------------------------
Ethanol 7.0
1,3-butylene glycol 5.0
Concentrated glycerin 5.0
Polyethylene glycol 1000 1.0
Lysolecithin 0.3
Polyoxyethylene hydrogenated castor oil (40 EO) 0.5
Polyglycerin diisostearate 0.5
Rhodendrol-D-glucoside 2.0
Ethyl glucoside (isomer mixture) 0.2
Sodium hyaluronate (* 1) 0.3
Dimethylsilanol hyaluronate 0.2
Carrageenan 0.2
Phenoxyethanol 0.3
Soymilk fermented extract (* 34) 0.1
Dutch pepper extract (* 35) 0.1
Ages extract (* 36) 0.1
Prune extract (* 37) 0.1
Black tea extract (* 38) 0.1
Oolong tea extract (* 39) 0.1
Seaweed extract (* 40) 0.1
Bukuryo extract (* 41) 0.1
Carrot extract (* 42) 0.1
Caffeine (* 43) 0.1
Arnica extract (* 44) 0.1
Ginkgo biloba extract (* 45) 0.1
Chamomile extract (* 46) 0.1
Clara extract (* 47) 0.1
SOHAKUHI EXTRACT (* 48) 0.1
Maronier extract (* 49) 0.1
Purified water residue * 34; Fermented soymilk (Sansho Pharmaceutical Co., Ltd.)
* 35; WATERCRESS KB (made by Silab)
* 36; Agetsu Extract BG-R (Maruzen Pharmaceutical Co., Ltd.)
* 37; Prune extract WC (Maruzen Pharmaceutical Co., Ltd.)
* 38; Black tea liquid (Ichimaru Falcos)
* 39; Falco Rex Oolong E (Ichimaru Falcos)
* 40: Phyco ARL EDTA (manufactured by Codif)
* 41: Falco Rex Bukuryo B (Ichimaru Falcos)
* 42: Falco Rex Carrot B (Ichimaru Falcos)
* 43: Chanomoto (Shiratori Pharmaceutical Co., Ltd.)
* 44; Arnica extract BG (Maruzen Pharmaceutical Co., Ltd.)
* 45: Ginkgo biloba extract BG (Maruzen Pharmaceutical Co., Ltd.)
* 46; Chamomile extract BG-J (Maruzen Pharmaceutical Co., Ltd.)
* 46: Falco Rex Clara B (Ichimaru Falcos)
* 48; Falco Rex Sohakuhi BG (manufactured by Ichimaru Falcos)
* 49; Maronnier extract BG-J (manufactured by Maruzen Pharmaceutical Co., Ltd.)

  Application Examples 1 to 6 were excellent in the stability of the preparations, and all were excellent when evaluated by the above effect test method.

  In addition, the composition of the fragrance | flavor used in said application example is shown below.

Claims (2)

(A) rhododendrol represented by the following general formula (1) or a derivative thereof;

(In the formula, R is a group selected from a hydrogen atom, an acyl group having 2 to 20 carbon atoms, or a monosaccharide or disaccharide residue.)
(B) ethyl glucoside ;
(C) A skin external preparation characterized by containing mucopolysaccharide . (A) Rhododendrol or a derivative thereof is 0.5 to 5.0% by mass, (b) Ethyl glucoside is 0.01 to 1.0% by mass, and (c) Mucopolysaccharide is 0.001 to 1.0%. The external preparation for skin according to claim 1, comprising a mass% .