JP2001002551A - Agent for increasing hyaluronic acid content of horny layer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject agent which can increase the hyaluronic acid content of the horny layer to optimize the water environment and hardness of the horny layer, allows to expect an effect for preventing rough skins and wrinkles, is stable in preparations, and is useful for skin cosmetics, by including N-acetylglucosamine. SOLUTION: This agent for increasing the hyaluronic acid content of a horny layer comprises N-acetylglucosamine. The agent is preferably added to a skin cosmetic preferably in an amount of 0.001 to 10%, especially preferably 0.01 to 5%, based on the total amount of the cosmetic composition. The agent may preferably further be compounded with a polyhydric alcohol such as 1,3-butylene glycol, a vitamin derivative such as an ascorbic acid phosphoric acid ester salt, an anionic surfactant such as N-stearoyl-L-glutamic acid salt, and so on.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention is intended to optimize the moisture environment of the stratum corneum and the hardness of the stratum corneum by increasing the amount of hyaluronic acid in the stratum corneum, to prevent rough skin and wrinkles, It relates to a stratum corneum hyaluronic acid level enhancer. Further, the present invention relates to a skin cosmetic containing the enhancer.

[0002]

2. Description of the Related Art The stratum corneum is located at the outermost layer of the skin and is a structure in which dead cells are deposited in layers by keratinization of epidermal cells.
Further, it is known that the moisture and physical strength of the stratum corneum play an important role in the flexibility of the stratum corneum and the barrier of external foreign substances, and are involved in the formation of rough skin and wrinkles. Up to now, the maintenance of moisture in the stratum corneum has been performed by applying a humectant or promoting the synthesis of intercellular lipids. In particular, hyaluronic acid is used as a representative of a humectant because of its high moisturizing ability, and a derivative having a high affinity for the stratum corneum has been developed recently (Japanese Patent Laid-Open No. 9-716).
02 publication). However, it is clear that the moisturizing ability decreases rapidly with the lapse of time due to washing or metabolism of the stratum corneum when the moisturizing agent is applied from the outside, and it has been desired that the moisturizing ability be maintained for a longer time. Therefore, we thought that by increasing the amount of hyaluronic acid present in the normal stratum corneum, it would be possible to supply hyaluronic acid in the stratum corneum from the inside of the skin, and examined various materials that actually increase the amount of hyaluronic acid in the stratum corneum. . Hyaluronic acid has not previously been considered to be present in the normal stratum corneum [J. Invest. Dermatol. 90: 412-141 (1988), JC
ell Biol. 108: 1557-1565 (1989), Histochemistry 98: 1
05-112 (1992), J. Invest.Dermatol. 102: 385-389 (199
4), J. Invest. Dermatol. 109: 219-224 (1997)] are all results obtained by tissue staining with a hyaluronic acid-binding protein, and do not actually quantify the hyaluronic acid in the stratum corneum. We actually quantified the amount of hyaluronic acid in the normal stratum corneum by using HAase and HPLC for the first time, and proved that hyaluronic acid was present in the stratum corneum.

[0003]

SUMMARY OF THE INVENTION In view of the above circumstances, the inventors of the present invention intend to prevent various types of substances by increasing the amount of hyaluronic acid in the stratum corneum to prevent wrinkles and rough skin. As a result of the study, it was found that N-acetylglucosamine increases the amount of hyaluronic acid in the stratum corneum, and the present invention was completed. An object of the present invention is to provide an acid amount enhancer.

[0004]

The above-mentioned object is achieved by a stratum corneum hyaluronic acid level enhancer containing N-acetylglucosamine as an active ingredient. It is also achieved by a skin cosmetic comprising the enhancer.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION As the N-acetylglucosamine according to the present invention, any of synthetic products, fermentation products, degradation products obtained from the degradation of chitin such as crabs and shrimps, etc. can be used, and those which are particularly limited is not.

[0006] The amount of the stratum corneum hyaluronic acid enhancer of the present invention to be incorporated into skin cosmetics is sufficient to have the effect of increasing the stratum corneum hyaluronic acid content, and since the color and odor are hardly produced, the composition It is preferably 0.001 to 10%, and particularly preferably 0.01 to 5%, based on the total amount.

[0007] In addition to the above, in addition to the above, color pigments such as tar dyes, iron oxide, preservatives such as paraben and phenoxyethanol, dimethylpolysiloxane, methylphenylpolysiloxane, cyclic Silicone oils such as silicon, hydrocarbons such as paraffin and petrolatum, olive squalane, rice squalane, rice germ oil,
Vegetable oils such as jojoba oil, castor oil, safflower oil, olive oil, macadamia nut oil, sunflower oil, waxes such as beeswax, mocro, carnauba wax, octyl dodecyl myristate, cetyl palmitate, isostearyl isostearate, and esters such as isopropyl myristate oil,
Lower alcohols such as ethanol, cetanol, behenyl alcohol, stearyl alcohol, higher alcohols such as long-chain branched aliphatic alcohols, cholesterol, phytosterols, branched fatty acid cholesterol esters,
Sterols and derivatives such as macadamia nut fatty acid phytosteryl ester, processing oils such as hardened oil, stearic acid, myristic acid, isostearic acid, oleic acid,
Higher fatty acids such as iso-type long-chain fatty acids and anteiso-type long-chain fatty acids; terpenes such as limonene and hydrogenated bisabolol; Triglycerides, such as
Anionic surfactants such as sodium cetyl sulfate, N-stearoyl-L-glutamate, polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene polyhydric alcohol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyvalent Nonionic surfactants such as alcohol fatty acid ester, polyglycerin fatty acid ester, modified silicone, sucrose ester, etc., cationic surfactants such as tetraalkylammonium salts, amphoteric surfactants such as betaine type, sulfobetaine type and sulfoamino acid type , Lecithin, lysophosphatidylcholine, ceramide, natural surfactants such as cerebroside, pigments such as titanium oxide and zinc oxide, antioxidants such as dibutylhydroxytoluene, sodium chloride, magnesium chloride, sodium sulfate, and nitric acid Potassium, sodium sulfate,
Sodium metasilicate, inorganic salts such as calcium chloride, sodium citrate, potassium acetate, sodium succinate,
Organic acids and salts thereof such as sodium aspartate, sodium lactate, dichloroacetic acid, mevalonic acid, and glycyrrhizic acid; organic amines such as ethanolamine hydrochloride, ammonium nitrate, arginine hydrochloride, diisopropylamine salt, urea, and decarboxycarnosine; Chelating agents such as edetic acid, xanthan gum, carboxyvinyl polymer, carrageenan, pectin, alkyl-modified carboxyvinyl polymer, thickeners such as agar, neutralizing agents such as potassium hydroxide, diisopropanolamine, triethanolamine, hydroxymethoxybenzophenone UV absorbers such as sulfonates, dipropylene glycol,
Polyhydric alcohols such as 1,3 butylene glycol, glycerin, propylene glycol, sorbitol, malbitol, diglycerin, raffinose, various amino acids,
Vitamins such as ascorbic acid, biotin, and tocopherol, and vitamin derivatives such as ascorbic acid sulfate, ascorbic acid phosphate, and tocopherol nicotinate can be appropriately blended within a range that achieves the object of the present invention.

Further, dermal hyaluronic acid production promoters such as N-methyl-L-serine, yeast extract, etc .; hyaluronic acid decomposition inhibitors such as Kuritake extract, Kurokawa extract, Mocking extract, Asenyaku extract and Clove extract; diisopropylamine Keratinizing agents such as dichloroacetic acid, niacin, mevalonic acid, hot spring water, sodium metasilicate,
The effect of preventing rough skin and wrinkles is further enhanced by appropriately blending barrier enhancers such as β-hydroxy-γ-aminobutyric acid and mevalonic acid, and humectants such as hyaluronic acid, glucosamine, glucuronic acid, glycerol, urea, and polyhydric alcohol. Increase.

[0009]

The present invention will be described below in detail with reference to Test Examples and Formulation Examples.

Test Example 1 The back of a male (12 weeks old) hairless mouse (HR-1) was punched out to a fixed area, immersed in PBS at 60 ° C. for 30 seconds, and the epidermis and dermis were separated. The separated epidermis was treated with 0.5% trypsin to isolate the stratum corneum. The isolated dermis, epidermis and stratum corneum were degreased with acetone, dried with nitrogen gas, and defatted dry weight was measured. After heating in 50 mM Tris-HCl pH 7.8 at 100 ° C. for 20 minutes, the mixture was homogenized with a glass homogenizer, pronase was added to a final concentration of 1%, and the protein was digested at 40 ° C. for 1 week. After the protein digestion, a quarter amount of 50% trichloroacetic acid was added, and the insoluble matter was removed by centrifugation. Centrifuge supernatant for 10
Neutralized with N-NaOH, desalted with Sephadex G-25, and lyophilized. The method for determining hyaluronic acid is based on the method of Maeda et al.
(1998) Vol.46 (suppl.) P125). The obtained dried product is treated with actinomycetes hyaluronidase in 0.1 M Na acetate buffer (pH 6.0) (2.5 TRU), and unsaturated tetrasaccharides and unsaturated hexasaccharides, which are degradation products derived from hyaluronic acid, are separated by HPLC. Thereafter, the cells were fluorescently labeled with 2-cyanoacetamide, and detected and quantified.

[Table 1] Amount of hyaluronic acid (n = 5) (mg / g dry weight) SE ------------------------------------ −−−− dermis 0.739 0.03 epidermis 0.015 0.0015 stratum corneum 0.022 0.0029

As shown in Table 1, it became clear that the stratum corneum contained hyaluronic acid equivalent to that of the epidermis.

Test Example 2 The skin softness of a hairless mouse (HR-1) male (38 to 39 weeks old) was measured with a Cutometer. After the measurement, a 1% N-acetylglucosamine / 0.5% NP-15 solution (Example 1) was applied to the back of the hairless mouse once a day for 50 weeks at a frequency of 5 days a week for 4 weeks. As a control group, a 0.5% NP-15 solution (Comparative Example 1) was used. The day after the final application (42 to 43 weeks of age), the flexibility after application was measured with a Cutometer, and the skin was collected. The skin punched out to a fixed area was immersed in PBS at 60 ° C. for 30 seconds to separate epidermis and dermis. The separated epidermis was treated with 0.5% trypsin to isolate the stratum corneum. The isolated stratum corneum was degreased with acetone, dried with nitrogen gas, and the defatted dry weight was measured. Further 50mM Tr
After heating at 100 ° C. for 20 minutes in is-HCl pH7.8, the mixture was homogenized with a glass homogenizer, pronase was added to a final concentration of 1%, and the protein was digested at 40 ° C. for 1 week. After the protein digestion, a quarter amount of 50% trichloroacetic acid was added, and the insoluble matter was removed by centrifugation. The centrifuged supernatant was neutralized with 10N-NaOH, desalted with Sephadex G-25, and concentrated. The obtained concentrate was treated with actinomycetes hyaluronidase, and the hyaluronic acid oligosaccharide as a degradation product was separated by HPLC, followed by fluorescent labeling with 2-cyanoacetamide, detection and quantification.

[Table 2] Flexibility (mm) n = 15 (μg / mg) Stratum corneum HA amount after application n = 5 Before application After application Comparative Example 1 0.197 ± 0.031 0.177 ± 0.025 0.0342 ± 0.0147 Example 1 0.163 ± 0.027 0.189 ± 0.039 0.0426 ± 0.0128

From Table 2, it is apparent that the application of N-acetylglucosamine increases the amount of hyaluronic acid in the stratum corneum and improves the flexibility of the stratum corneum.

Hereinafter, application examples (skin cosmetics) of the stratum corneum hyaluronic acid content enhancer of the present invention will be described.

Formulation Examples 1 to 3 (Skin Cream) N-acetylglucosamine was blended with each of the following compositions to prepare skin creams (Formulation Examples 1 to 3).

(1) Composition Formulation Example 1 Formulation Example 2 Formulation Example 3 (A) Stearic acid 110 Isostearic acid 01 Glycerin monostearate 22 2 Behenyl alcohol 2 22 1 Sorbitan sesquioleate 1 11 N-stearoylphytosphingosine 0.1 0.1 0.1 Hydrogenated lecithin 0.1 0.1 0.1 Plant squalane 5.55 Octyldodecyl myristate 5.55 (B) N -Acetylglucosamine 0.01 0.1 1.0 1,3-butylene glycol 5 10 5 Concentrated glycerin 5.55 Methyl parahydroxybenzoate 0.2 0.2 0.2 Ascorbic acid phosphate Na salt 0.2 0. 2 0.2 γ-aminobutyric acid 0.1 0.1 0.1 N-stearoylglutamic Acid Na 0.2 0.2 0.2 Alkyl-modified carboxyvinyl polymer 0.05 0.05 0.005 Nicotinamide 0.1 0.1 0.1 Sarcosine 0.1 0.1 0.1 Purified water residue Amount Remaining Remaining

(2) Preparation Method The components (A) and (B) are each dissolved by heating to 80 ° C., mixed, cooled with stirring, and cooled to 30 ° C.
A skin cream was prepared.

Formulation Examples 4 to 6 (Lotion) N-acetylglucosamine was blended with the following composition to prepare lotions (Application Examples 4 to 6).

(1) Composition Formulation Example 4 Formulation Example 5 Formulation Example 6 N-acetylglucosamine 0.1 0.3 1.0 1,3-butylene glycol 505 Dipropylene glycol 0 555 Raffinose 111 ethanol 0 0 1 Phenoxyethanol 0.2 0.2 0.2 Pectin 0.0 0.05 Xanthan gum 0.0 0.1 Sodium citrate 0.05 0.05 0.05 0.05 Horsetail extract (ethanol extraction) 0.1 0.10 .1 diisopropylamine dichloroacetic acid 0.2 0.2 0.2 γ-amino-β-hydroxybutyric acid 0.2 0.2 0.2 sodium hyaluronate 0.001 0.001 0.001 dipotassium glycyrrhizinate 0.2 0.2 0.2 Mushroom extract (ethanol extraction) 0.05 0.05 0.05 Decarboxycarnosi Hydrochloride 0.05 0.05 0.05 Perfume 0.02 0.02 0.02 Purified water Balance remaining residual

(2) Preparation method Each component was mixed and dissolved, and stirred to prepare a lotion.

Formulation Examples 7 to 9 (Gel) N-acetylglucosamine was blended with each of the following compositions to prepare gels (Formulation Examples 7 to 9).

(1) Composition Formulation Example 7 Formulation Example 8 Formulation Example 9 (A) Decamethylcyclopentasiloxane 10 10 10 Isostearyl Isostearate 100 Olive Oil 0 10 0 Macadamia Nut Oil 0 0 1 Eucalyptus Oil 0.1 0 0 .1 Hexyldecanol 1 0.10 POE hydrogenated castor oil (60EO) 22 2 Spherical silicon powder (Note 1) 115 (B) N-acetylglucosamine 0.1 0.1 0.1 Glucosamine 0 00 Glucuronic acid 00 0.1 1,3-butylene glycol 5 10 5 Sorbitol solution 3 3 3 Polyethylene glycol 4000 11 1 Carboxyvinyl polymer 0.2 0.2 0.2 Sugar ceramide (Note 2) 0.1 0.1 0.1 Methyl parahydroxybenzoate 0.2 0.2 0.2 Mevalonolactone 0.5 0.5 0. Disodium edetate 0.02 0.02 0.02 Potassium hydroxide 0.05 0.05 0.05 0.05 Purified water Remaining Remaining Remaining Note 1: Tospearl Silicon 145A Note 2: Kibun Food Chemical Bioceramide

(2) Preparation Method The components (A) and (B) are each heated and dissolved at 60 ° C., mixed, cooled with stirring, and cooled to 30 ° C.
A cream was prepared. Formulation Examples 10 to 12 (Lipophilic Cream) N-acetylglucosamine of Example 1 was blended with the following composition to prepare a lipophilic cream (Application Examples 10 to 12).

(1) Composition Formulation Example 10 Formulation Example 11 Formulation Example 12 (A) Co-modified silicon (Note 3) 2 22 POE-modified silicon dispersion (Note 4) 0 20 Squalane 0 0 10 Decamethylcyclopentasiloxane 15 20 10 Methylpolysiloxane 5 2 3 Long-chain branched fatty acid cholesteryl (Note 5) 03 Silicon elastomer dispersion (Note 6) 5 20 (B) N-acetylglucosamine 0.1 0.1 0.1 Niacin 0 .100 Kurita mushroom extract (ethanol extraction) 0 0.10 Sodium chloride 111 Dipropylene glycol 55 5 Concentrated glycerin 55 55 Raffinose 11 1 Methyl paraoxybenzoate 0.3 0.3 0.3 Licorice Extract (ethanol extraction) 0.1 0.1 0.1 N-methyl-L-serine 0.5 0.5 0.5 Water Remaining Remaining Remaining Remaining Note 3: Gold Schmidt ABIL EM90 Note 4: Toray Dow Corning Silicone Silicon BY22-008 Note 5: Nippon Seika YOFCO CLE-NH Note 6: Toray Dow Corning Silicone Trefill

(2) Preparation method The components (A) and (B) are each heated and dissolved at 60 ° C., mixed, cooled with stirring, and cooled to 30 ° C.
A lipophilic cream was prepared.

[0028]

As described above, it is apparent that the present invention can provide a stratum corneum hyaluronic acid enhancer which is stable in a preparation.

 ────────────────────────────────────────────────── ─── Continuing from the front page (72) Inventor Shintaro Inoue 5-28, Kotobukicho, Odawara-shi, Kanagawa F-term in Kanebo Co., Ltd. Basic Research Laboratory 4C083 AA082 AA112 AA122 AB032 AB332 AC022 AC072 AC092 AC102 AC122 AC132 AC152 AC242 AC262 AC302 AC352 AC422 AC432 AC442 AC482 AC532 AC542 AC622 AC642 AC662 AC812 AC842 AC852 AD042 AD092 AD152 AD162 AD172 AD201 AD202 AD212 AD331 AD332 AD352 AD372 AD492 AD532 AD572 AD642 CC02 CC04 CC05 DD31 DD41 EE12 FF05

Claims (4)

[Claims] 1. A stratum corneum hyaluronic acid level enhancer comprising N-acetylglucosamine. 2. A skin cosmetic comprising the stratum corneum hyaluronic acid content enhancer according to claim 1. 3. A skin cosmetic comprising a stratum corneum hyaluronic acid level enhancer. 4. A method of increasing skin flexibility by increasing the amount of stratum corneum hyaluronic acid (excluding medical practice).