JP2000063256A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a preparation for external use for skin that has high moisture retention effect in skin and excellent improvement of darkened and dulled skin by using acetylated hyaluronic acid and a specific amino acid derivative or the like as active ingredients. SOLUTION: The objective preparation for external use for skin includes (A) an acetylated hyaluronic acid bearing 2-4 acetyl groups per the structural unit of hyaluronic acid and (B) at least one selected from α-amino acid derivative represented by the formula (R1 is H, a lower alkyl or the like; R2 and R3 are each H, an acyl or the like) or its salt or its carboxylic ester or its quaternary ammonium salt in which one more lower alkyl group bonds to the nitrogen atoms in case of R2 and R3 = lower alkyl groups, as active ingredients. In a preferred embodiment the amount of the component A is 0.0001-10.0 wt.% and the compound of the formula is 0.01-10.0 wt.% based on the total amount of the preparation. This external preparation can be combined with hydrocarbons, fat and oil and the like.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention is an invention in the technical field relating to a skin external preparation. More specifically, the present invention provides
It is an invention relating to a skin external preparation capable of exerting a high moisturizing effect on the skin and an effect of improving dullness of the skin by combining and combining specific components.

[0002]

2. Description of the Related Art Dullness of the skin has hitherto been a major cause of worries about women's skin and is a major cosmetic problem. Nevertheless, it cannot be denied that the phenomenon of dull skin itself is vague and difficult to understand.

At least it is clear that dull skin is a particular visual phenomenon. That is, in the state where it is recognized as dull skin, the entire face,
In areas around the eyes and cheeks, the redness of the skin decreases and the yellowness increases, the glossiness of the skin decreases, and the shadows due to the unevenness of the skin surface reduce the brightness and make it appear dark. It is recognized that the boundaries are unclear.

As a cause of such dull skin,
It is assumed that the following items (1) to (4) are involved, and that the above-mentioned specific phenomenon of skin dullness appears when these factors are involved singly or in plural. Decrease in redness of skin color due to poor circulation to the surface Unclear plaque formation or microscopic variegation pigmentation Effect of fine irregularities on skin surface caused by decreased elasticity of skin Growth and peeling of stratum corneum, etc. Decrease in transparency (light transmission) due to diffused reflection on the skin surface, decrease in gloss Change in skin color due to the yellowing cycle of the skin Dullness due to dirt such as dust, sweat and sebum

In recent years, various attempts have been made to improve the dullness of the skin. For example, the coordination of the formation of the stratum corneum, which is the dead cells of the epidermal cells, and its loss due to physiological detachment is necessary to maintain skin with a beautiful appearance, and desmosomes From the viewpoint of being seen as an essential structure for keratinocyte adhesion, a skin external preparation intended to improve the dullness of skin by degrading this desmosome has already been provided.

[0006]

However, while the external preparation for skin provided for the purpose of improving the dullness of the skin has an excellent effect of improving the dullness of the skin, moisture on the skin is recognized. The effect of preventing the volatilization of the skin was not recognized so much, and it was not expected to prevent the deterioration of the gloss of the skin due to the diffused reflection on the skin surface, which is shown by the above-mentioned element of dull skin.

[0007]

Means for Solving the Problems The present inventor has conducted extensive studies to solve the above problems. As a result, the external preparation for skin prepared by combining acetylated hyaluronic acid and a specific amino acid derivative-based compound as an active ingredient has a high moisturizing effect on the skin and is also excellent in improving the dullness of the skin. The inventors have found that and completed the present invention.

That is, the present invention provides (A) an acetylated hyaluronic acid in which the number of substituted acetyl groups is 2 to 4 per hyaluronic acid constitutional unit, and (B) an α-amino acid represented by the following formula (I): A derivative or a salt thereof or a carboxylic acid ester, or a quaternary ammonium compound in which one lower alkyl group is further bonded to the nitrogen atom of the following formula (I) when R ² and R ³ are lower alkyl groups: The invention is to provide an external preparation for skin containing one or more as an active ingredient.

[0009]

[Chemical 2]

[In the formula, R ¹ is a hydrogen atom or an unsubstituted or substituted lower alkyl group, and the substituent in the substituted lower alkyl group is a hydroxyl group; A mercapto group which may be substituted; a lower alkyl group, a lower acyl group, an amidino group, an amino group which may be substituted with an N-mono- or N, N′-di-lower alkylated amidino group; which may be substituted with a hydroxyl group A good phenyl group; a 5-membered multiple cyclic group having one or two nitrogen atoms in the ring and optionally condensed with a benzene ring or a carbamoyl group, and R ² and R ³ are independent of each other. A hydrogen atom, a lower alkyl group or an acyl group, or one of R ² and R ³ and R ¹ together form a propane-1,3-diyl group, 2-hydroxypropane-1. , 3-D Forming the Le radical

The term "lower" used in the present invention in which the number of carbon atoms in the molecule is used as an index means that the number of carbon atoms in the molecule is 1 to 6, and the carbon skeleton is linear. If it is, it does not matter whether it is branched.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below. The acetylated hyaluronic acid to be added to the skin external preparation according to the present invention (hereinafter referred to as the skin external preparation of the present invention) has a substitution number of the acetyl group represented by the following general formula (II) of 2 to 2 per hyaluronic acid constitutional unit. 4 is a hyaluronic acid derivative.

[0013]

[Chemical 3] [Wherein, R ⁴ , R ⁵ , R ⁶ , and R ⁷ are hydrogen atoms or ester-bonded acetyl groups, and in each repeating structure, at least two of R ^{4 to} R ⁷ are acetyl groups. It is a base. R ⁸ is a hydrogen atom or an alkali metal atom]

The acetylated hyaluronic acid which can be blended in the external preparation for skin of the present invention is 10,000 to 1 in terms of hyaluronic acid.
It is preferable to select one having a molecular weight of about, 000,000.

The acetylated hyaluronic acid can be produced, for example, according to the production method described in JP-A-6-9707. That is, for example, a method of dispersing powdered hyaluronic acid in acetic acid and adding trifluoroacetic anhydride as a catalyst to proceed the acetylation reaction, or similarly, dispersing powdered hyaluronic acid in acetic acid and then adding p
-Toluenesulfonic acid is added and acetic anhydride is further added to proceed the acetylation reaction, or hyaluronic acid is suspended in an acetic anhydride solvent and concentrated sulfuric acid is added thereto to proceed the acetylation reaction, etc. Manufactured by.

The amount of acetylated hyaluronic acid in the external preparation for skin of the present invention is 0.0 with respect to the total external preparation for skin.
001 to 10.0% by weight or less is preferable, and particularly 0.0
01 to 5.0% by weight is preferable. If the blending amount is less than 0.0001% by weight based on the whole skin external preparation, it will be substantially difficult to exert a moisturizing effect in the skin external preparation, which is not preferable, and conversely 10.0% by weight. If the content is exceeded, a sticky feeling or a filmy feeling is generated, and the feeling of use as an external preparation for the skin tends to be rather deteriorated, which is not preferable.

In the external preparation for skin of the present invention, a specific amino acid derivative compound represented by the above formula (I) is added as an active ingredient in combination with the acetylated hyaluronic acid. In the external preparation for skin of the present invention, by blending this amino acid derivative compound (I), the residual rate of desmoglein in the horny layer sheet of the skin is reduced, and, for example, a keratin exfoliating effect that accelerates turnover of the horny layer. Etc. and acts to provide fresh and fresh skin.

In the amino acid derivative compound (I),
The "lower alkyl group" means an alkyl group having 1 to 6 carbon atoms as described above. For example, R
Specific examples of the unsubstituted lower alkyl group which ¹ may have include, for example, a methyl group (amino acid derivative compound (I)
Is an alanine or a derivative thereof), an ethyl group, a propyl group, an isopropyl group (related when the amino acid derivative compound (I) is a valine or a derivative thereof), a 2-methylpropyl group ( Amino acid derivative compound (I) is related to leucine or a derivative thereof), 1-methylpropyl group (related to amino acid derivative compound (I) is isoleucine or a derivative thereof), n- A butyl group, an n-pentyl group, an n-hexyl group and the like can be mentioned.

Further, the substituted lower alkyl group which R ¹ may have means an alkyl group in which the hydrogen atom of the above lower alkyl group is substituted by the same or different substituents. The substituent in the substituted lower alkyl group is
As described above, a hydroxyl group, a mercapto group optionally substituted with a lower alkyl group, a lower alkyl group, a lower acyl group, an amidino group, N-mono- or N, N'-
An amino group that may be substituted with a di-lower alkylated amidino group, a phenyl group that may be substituted with a hydroxyl group, or one or two nitrogen atoms in the ring, and the benzene ring is fused Is a 5-membered multiple cyclic group or a carbamoyl group.

When the substituent is a hydroxyl group, typical examples of the substituted lower alkyl group which R ¹ may have include, for example, hydroxymethylmethyl (amino acid derivative compound (I) is serine or its compound). 1-hydroxyethyl (related to the case where the amino acid derivative compound (I) is threonine or a derivative thereof) and the like.

When the substituent is a mercapto group which may be substituted with a lower alkyl group, typical examples of the substituted lower alkyl group which R ¹ may have include, for example, a mercaptomethyl group (amino acid). And the 2-methylthioethyl group (related when the derivative compound (I) is cysteine or a derivative thereof) and the 2-methylthioethyl group (related when the amino acid derivative compound (I) is methionine or a derivative thereof).

The substituent is a lower alkyl group (preferably a methyl group or an ethyl group), a lower acyl group (preferably a formyl group or an acetyl group), an amidino group [-C (= NH) -N.
H ₂ ], an N-mono- or N, N′-di-lower alkylated amidino group, which is an amino group optionally substituted, is a typical substituted lower alkyl group for R ^1. Examples thereof include 4-aminobutyl group (related when the amino acid derivative compound (I) is lysine or its derivative), 3-amidino group (or carbamimidoyl group: -C (= NH)). —NH ₂ ), an aminopropyl group (related to the case where the amino acid derivative compound (I) is arginine or a derivative thereof) and the like.

The substituent is a phenyl group which may be substituted with a hydroxyl group, has one or two nitrogen atoms in the ring,
When the benzene ring is a 5-membered heterocyclic group which may be condensed, typical examples of the substituted lower alkyl group which R ¹ may have include, for example, a phenylmethyl group (an amino acid derivative-based compound). (Related to the case where (I) is phenylalanine or a derivative thereof), 4-hydroxyphenylmethyl group (amino acid derivative compound (I)
Is a tyrosine or a derivative thereof), (1 H -imidazol-4-yl) methyl group (related when the amino acid derivative compound (I) is histidine or a derivative thereof), (1 H -indol-3-yl) methyl group (amino acid derivative-based compound (I)
Is related to the case of tryptophan or a derivative thereof) and the like.

The substituent is a carbamoyl group (--CON
When it is H ₂ ), typical examples of the substituted lower alkyl group which R ¹ may take include, for example, when the carbamoylmethyl group (the amino acid derivative compound (I) is asparagine or a derivative thereof: Related), 2
-Carbamoylethyl (amino acid derivative compound (I)
Is relevant to glutamine or a derivative thereof).

The lower alkyl group which R ² or R ³ can take is the same as the lower alkyl group already defined for R ¹ . The acyl group R ² or R ³ can be taken, formyl group, acetyl group, may be mentioned lower acyl groups such as propionyl group, the R ² or R
³ may be a so-called intermediate acyl group or higher acyl group (hereinafter referred to as higher acyl group). Examples of the higher acyl group that R ² or R ³ can have include a residue derived from a fatty acid having 7 to 26 carbon atoms. Fatty acids from which such higher acyl groups are derived are preferably derived from natural lipids, for example, saturated sources such as rice bran oil, wax, lanolin, coconut oil, palm oil, and milk fat. Fatty acids such as cerotic acid, lignoceric acid, behenic acid, arachidic acid, stearic acid, palmitic acid, myristic acid, lauric acid, capric acid, caprylic acid, caproic acid, butyric acid and the like can be mentioned. Further, unsaturated fatty acids whose origins are terrestrial animal fats (particularly beef tallow), marine animal oils (particularly fish liver oil), and other vegetable oils (eg cilantro oil, evening primrose seed oil), such as palmitoleic acid and petroselinic acid, Oleic acid, elaidic acid,
Linoleic acid, γ-linolenic acid, arachidonic acid and the like can be mentioned as the fatty acid from which the above-mentioned higher acyl group is derived. Further, these fatty acids may have a hydroxyl group such as ricinoleic acid and α-oxylinolenic acid. An embodiment in which R ² and R ³ are hydrogen atoms at the same time is also a preferred embodiment.

Further, one of R ² and R ³ is R ¹
Together with a nitrogen atom and a carbon atom to which they are respectively attached, a residue forming a 5-membered ring, for example, a propane-1,3-diyl group (—CH ₂ CH ₂ CH ₂ —)
(Amino acid derivative compound (I) is associated when proline or derivatives thereof), 2-hydroxy-1,3-diyl (-CH ₂ CH (OH) CH
_2- ) (related when the amino acid derivative compound (I) is 4-hydroxyproline or a derivative thereof), 1-hydroxypropane-1,3-diyl group (-
_{CH (OH) CH 2 CH 2} -) ( amino acid derivative compounds (I) may be a relevant) when a 3-hydroxyproline or derivatives thereof.

The amino acid derivative compound (I) is
When either one of R ² and R ³ represents a lower acyl group, it may be a salt via a carboxyl group, and further, both R ² and R ³ are lower alkyl groups, When the carboxyl group is an ester (carboxylic acid ester), it may be a salt via the R ² (R ³ ) N-group. Typical examples of the former salt via a carboxyl group include ammonium salts and alkali metal salts such as sodium salts, lithium salts and potassium salts, and the latter R ² (R ³ ) N Representative examples of the salt via a group include, for example, hydrochloride, hydrobromide, phosphate, sulfate, organic sulfonate (eg, methanesulfonate, ethanesulfonate, etc.) ,
Organic carboxylates (eg, acetate, citrate, malate, succinate, tartrate, etc.) can be mentioned.

When the amino acid derivative compound (I) is in the form of a carboxylic acid ester, it may be a lower or higher alkanol (eg, methanol, ethanol,
Octanol, decanol, stearyl alcohol, octacosanol, etc.) and an ester formed from a carboxyl group. When R ² and R ³ are both lower alkyl groups (preferably methyl groups), a lower alkyl group (preferably methyl group) is further bonded to the nitrogen atom to which they are bonded,
A quaternary ammonium group may be formed (related when the amino acid derivative compound (I) is N, N, N-trimethylglycine or a derivative thereof).

As the amino acid derivative compound (I),
In general, those in the category of naturally-occurring α-amino acids can be conveniently used, but for α-amino acids other than glycine, L-type amino acid derivatives and their enantiomers (D-
Types) or their racemic forms can also be used conveniently.

The amount of the amino acid derivative compound (I) in the external preparation for skin of the present invention depends on the amount of the above-mentioned acetylated hyaluronic acid and the specific dosage form and specific purpose of the external preparation for skin of the present invention. It can be appropriately selected depending on the application, but generally 0.001-10.
0% by weight is preferable, and 0.01 to 10.0% by weight is particularly preferable. 0.001% by weight based on the total skin external preparation
If the blending amount is less than 1, it is not preferable because it is substantially difficult to exert the effect of improving the dullness of the skin.
Even if it is blended in excess of wt%, the effect of improving the dullness of the skin commensurate with the increase in the blending amount will not be recognized, and
It is not preferable because it tends to have a sticky feel.

In the external preparation for skin of the present invention, in addition to the above-mentioned essential components, one or more other components usually used in cosmetics and external preparations may be added to the above-mentioned essential components to impair the intended effect of the present invention. It can be appropriately blended unless otherwise specified, for example, hydrocarbons such as liquid paraffin, squalane, petrolatum; oils and fats such as macadamia nut oil, olive oil, lanolin; waxes such as jojoba oil, carnauba wax, candelilla wax,
Silicones such as dimethylpolysiloxane and methylphenylsiloxane; higher alcohols such as capryl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, cholesterol and phytosterol; capric acid, myristic acid, palmitic acid, stearic acid, behenic acid, lanolin fatty acid Higher fatty acids such as linoleic acid and linolenic acid;

Polyethylene glycol, glycerin, 1,
Moisturizing agents such as 3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, chitosan; cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl hydroxypropyl cellulose, methyl cellulose, carboxymethyl cellulose, quince seed, carrageenan, pectin, mannan, curdlan , Chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, heparan sulfate, tragacanth gum, keratan sulfate, chondroitin, xanthan gum, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, guar gum, dextran, kerato sulfate, locust bean gum, Succinoglucan, caronic acid, chitin, chitosan, carboxymethyl Chin, a thickener such as agar;

Lower alcohols such as ethanol; antioxidants such as butylhydroxytoluene, tocopherol and phytin; antibacterial agents such as benzoic acid, salicylic acid, sorbic acid, paraoxybenzoic acid alkyl ester and hexachlorophene; paraaminobenzoic acid type ultraviolet absorbers , Anthranilic acid type UV absorber, salicylic acid type UV absorber, cinnamic acid type UV absorber, benzophenone type UV absorber,
Sugar-based UV absorber, 3- (4'-methylbenzylidene) -d-camphor, 3-benzylidene-d, 1-camphor, urocanic acid, urocanic acid ethyl ester, 2-phenyl-5-methylbenzoxazole, 2 2,2'-hydroxy-5-methylphenylbenzotriazole, 2- (2'-hydroxy-5'-t-octylphenyl) benzotriazole, 2- (2'-hydroxy-5'-methylphenylbenzotriazole, dibenzalazine, UV absorbers such as dianisoylmethane, 4-methoxy-4'-t-butyldibenzoylmethane, 5- (3,3-dimethyl-2-norbornylidene) -3-pentan-2-one;

Organic acids such as acyl sarcosine acid (eg sodium lauroyl sarcosine), glutathione, citric acid, malic acid, tartaric acid, lactic acid; vitamin A and its derivatives, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, Vitamin B2 such as vitamin B2 and its derivative, vitamin B12, vitamin B15 and its derivative, vitamin C such as ascorbic acid, ascorbic acid sulfate (salt), ascorbic acid phosphate (salt), and ascorbic acid dipalmitate
E, α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E such as vitamin E acetate
, Vitamins D, vitamin H, pantothenic acid, vitamins such as pantethine;

Nicotinic acid amide, benzyl nicotinate,
γ-Oryzanol, allantoin, glycyrrhizic acid (salt), glycyrrhetinic acid and its derivatives, hinokitiol, bisabolol, eucalptone, thymol, inositol, saikosaponin, carrot saponin, saponins such as hechimasaponin, muclodisaponin, pantothenyl ethyl ether. , Ethinyl estradiol, tranexamic acid, arbutin, cepharanthin, placenta extract, etc .; Rumex, Clara, Kouhone,
Orange, sage, yarrow, mallow, senburi, thyme, touki, spruce, birch, horsetail, loofah, horse chestnut, yukinoshita, arnica, lily, mugwort,
Extracts of plants such as peony, aloe, gardenia, sawara:

Various dyes, sorbitan monolaurate, sorbitan monopalmitate, sorbitan sesquioleate, sorbitan trioleate, polyoxyethylene sorbitan monolaurate, polyoxetylene sorbitan monostearate, polyethylene glycol monooleate, polyoxyethylene alkyl ether , Polyglycol diether, lauroyl diethanol amide, fatty acid isopropanol amide, maltitol hydroxy fatty acid ether, non-ionic activator such as alkylated polysaccharide, alkyl glucoside, sugar ester, stearyl trimethyl ammonium chloride, benzalkonium chloride, lauryl amine oxide Cationic surfactants such as sodium palmitate, sodium laurate, sodium laurate Potassium, potassium lauryl sulfate, alkyl sulfate, triethanolamine ether, turkey red oil,
Anionic surfactants such as linear dodecylbenzene sulfuric acid, polyoxyethylene hydrogenated castor oil maleic acid, and acylmethyl taurine, amphoteric surfactants, neutralizing agents, antioxidants, fragrances, purified water and the like can be added.

The dosage form of the external preparation for skin of the present invention is not particularly limited, and examples thereof include aqueous solution system, solubilizing system, emulsifying system, powder dispersion system, water-oil 2-layer system, water-oil-powder 3-layer system, and the like. The present invention can be applied to all dosage forms that can be used as an external preparation for skin. It is also used for pharmaceuticals such as ointments, quasi-drugs, basic cosmetics such as lotions, emulsions, creams, packs, make-up cosmetics such as lipsticks and foundations, and hair for shampoos, rinses, hair dyes, etc. There are many types of products and special cosmetics such as sunscreen.

[0038]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but the technical scope of the present invention should not be construed as being limited to these examples. In addition, unless otherwise specified, the compounding amount indicates the weight% with respect to the object in which the component is compounded. First, prior to the disclosure of each formulation example, the evaluation method adopted for the external preparation for skin of the present invention will be shown.

[Dullness-improving effect test] For each test product, 20 groups of female subjects in their 30s to 50s applied the test product to the face and cheeks twice a day (morning and evening) for 1 month. A continuous test was conducted. After the continuous use test, the effect of improving the dullness of the skin was evaluated by the test subject's self-confidence and the visual evaluation by a beauty technician (3 persons) (the evaluation items are "improvement of dullness", "improvement of transparency of skin", and "whiteness of skin". Improvement ")
Was evaluated. The evaluation was divided into 4 grades of excellent effect (3 points), effective (2 points), slightly effective (1 point) and no effect (0 point), and expressed by the average evaluation score between each subject and the beauty technician. .

[Moisture Evaporation Rate Test Based on Moisture Evaporation Rate] As a test for measuring the moisturizing effect, moisture evaporation was measured.
That is, 10 μl of the sample solution was dropped on a 2.0 × 2.0 cm filter paper, and the weight reduction was measured every 1 minute for 10 minutes, and the weight reduced per minute was determined. ◎: Moisture evaporation rate of less than 0.5 μg / min. ○: Moisture evaporation rate of 0.5 μg / min. Or more, 0.55 μ
Less than g / min. △: Moisture evaporation rate 0.55 μg / min. or more, 0.60
Less than μg / min. ×: Moisture evaporation rate 0.60 μg / min. or more

First, lotions (Examples 1 to 4 and Comparative Examples 1 to 5) having the formulations shown in Tables 1 (Examples) and 2 (Comparative Examples) below were prepared by a conventional method, and these lotions were prepared. The above-described dullness improving effect test and moisturizing effect test were performed on the test product. The results are shown in Tables 3 and 4 (a dullness improving effect test by a panel of ordinary people), 5 and 6 (a dullness improving effect test by a panel of beauty engineers), and Table 7 (described below). The results of the moisturizing effect test).

[0042]

[Table 1]

[0043]

[Table 2] In the examples and comparative examples of the formulations shown in Tables 1 and 2 above, acetylated hyaluronic acid having an acetyl degree of 3.7 and a molecular weight of 100,000 was used.

[0044]

[Table 3]

[0045]

[Table 4]

[0046]

[Table 5]

[0047]

[Table 6]

[0048]                               Table 7 ────────────────────────────────────                       Example 1 Example 2 Example 3 Example 4 ────────────────────────────────────   Results of moisturizing effect test ○ ○ ◎ ◎ ────────────────────────────────────                       Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 ────────────────────────────────────   Results of moisturizing effect test × × △ ○ ◎ ────────────────────────────────────

As shown in Tables 3 to 7, by combining alanine which is the amino acid derivative compound (I) and acetylated hyaluronic acid in combination, excellent synergistic effects of these components were obtained. It can be seen that the skin dullness improving effect and the moisturizing effect are exhibited. On the other hand, in the comparative examples, no example was found in which the skin dullness improving effect and the moisturizing effect were both exhibited and fully exerted.

Next, prescription examples of the skin external preparation of the present invention are shown (Examples 5 to 7). When the same tests as above were carried out on these products of the present invention, it was found that an excellent moisturizing effect was exhibited together with improvement of dullness of the skin.

[Example 5] Cream (% by weight) (1) Cetyl alcohol 5.0 (2) Stearic acid 3.0 (3) Vaseline 5.0 (4) Squalane 10.0 (5) Glycerol tri 2- Ethylhexanoic acid ester 7.0 (6) Dipropylene glycol 5.0 (7) Glycerin 5.0 (8) Propylene glycol monostearic acid ester 1.5 (9) Polyoxyethylene (20) cetyl alcohol ether 1.5 (10) Triethanolamine 1.0 (11) Evening primrose oil 1.0 (12) Acetylated hyaluronic acid 1.0 (Acetylation degree 3.1, molecular weight 200,000) (13) Serine 0.5 (14) Preservative Agent Proper amount (14) Antioxidant Proper amount (15) Perfume Proper amount (16) Purified water Residual <Production method> Add a moisturizer and alkali to the purified water,
Was adjusted to (aqueous phase). Next, the oil content is heated and dissolved, and then a surfactant, a preservative, an antioxidant and a fragrance are added,
The temperature was adjusted to 0 ° C. This was added to the above aqueous phase to carry out preliminary emulsification. The emulsified particles of this preliminary emulsion were homogenized with a homomixer and then deaerated, filtered and cooled to obtain a desired cream.

Example 6 Emulsion (% by weight) (1) Cetyl alcohol 1.0 (2) Beeswax 0.5 (3) Vaseline 2.0 (4) Squalane 6.0 (5) Dimethylpolysiloxane 2 0.0 (6) Ethanol 5.0 (7) Glycerin 4.0 (8) 1,3-Butylene glycol 4.0 (9) Polyoxyethylene (10) monooleate 1.0 (10) Glycerol monostearin Acid ester 1.0 (11) trimethylglycine 2.0 (12) acetylated hyaluronic acid 0.1 (acetylation degree 3.5, molecular weight 100,000) (13) alanine 1.0 (14) preservative proper amount ( 15) Coloring agent Proper amount (16) Perfume Proper amount (17) Purified water Residue <Production method> A moisturizer and a coloring agent were added to the purified water, and the temperature was adjusted to 70 ° C (water phase). Next, a surfactant, a preservative and a fragrance were added to the oil, and the temperature was adjusted to 70 ° C. This is added to the previous aqueous phase to carry out preliminary emulsification, xyloglucan and ethanol are added to this preliminary emulsion and stirred, and the homogenized emulsion particles are homogenized, followed by degassing, filtration and cooling. To obtain the desired emulsion.

[Example 7] Foundation (% by weight) (1) Talc 3.0 (2) Titanium dioxide 5.0 (3) Red iron oxide 0.5 (4) Yellow iron oxide 1.4 (5) Black iron oxide 0.1 (6) Polyoxyethylene sorbitan monostearate 0.9 (7) Triethanolamine 1.0 (8) Propylene glycol 5.0 (9) Hydroxyethyl cellulose 0.5 (10) Acetylated hyaluronic acid 0. 5 (degree of acetylation 3.3, molecular weight 400,000) (11) serine 0.5 (12) stearic acid 2.2 (13) isohexadecyl alcohol 7.0 (14) glyceryl monostearate 2.0 (15) ) Liquid lanolin 2.0 (16) Liquid paraffin 8.0 (17) Preservative Appropriate amount (18) Perfume Appropriate amount (19) Purified water Residue <Production method> Xyloglucan The dispersed propylene glycol was added to purified water and subjected to a homomixer treatment at 70 ° C., and then the remaining aqueous phase components were added and sufficiently stirred. Add the powder components that have been thoroughly mixed and pulverized to this while stirring,
A homomixer treatment was performed at 70 ° C. This was cooled with stirring, and a fragrance was added when the system reached 45 ° C., and finally degassed and filled in a container to obtain a desired foundation.

[0054]

EFFECTS OF THE INVENTION The present invention provides an external preparation for skin which has both an excellent effect of improving skin dullness and a moisturizing effect.

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4C083 AA082 AA122 AB232 AB242                       AB432 AC012 AC022 AC072                       AC092 AC102 AC122 AC182                       AC242 AC392 AC422 AC442                       AC542 AC581 AC582 AC691                       AD112 AD152 AD282 AD331                       AD332 AD512 CC02 CC05                       EE16

Claims (2)

[Claims] 1. An acetylated hyaluronic acid having (A) an acetyl group substitution number of 2 to 4 per hyaluronic acid constitutional unit, and (B) an α-amino acid derivative represented by the following formula (I) or a salt thereof. Alternatively, one or more quaternary ammonium compounds in which one lower alkyl group is further bonded to the nitrogen atom of the following formula (I) is effective when carboxylic acid ester or R ² and R ³ are lower alkyl groups. External preparation for skin containing as an ingredient: [In the formula, R ¹ is a hydrogen atom or an unsubstituted or substituted lower alkyl group, and the substituent in the substituted lower alkyl group is a hydroxyl group; mercapto which may be substituted with a lower alkyl group. Group; lower alkyl group, lower acyl group, amidino group, N-mono- or N, N '
An amino group optionally substituted with a di-lower alkylated amidino group; a phenyl group optionally substituted with a hydroxyl group; having 1 or 2 nitrogen atoms in the ring, and having a condensed benzene ring Is a 5-membered multiple cyclic group or a carbamoyl group, R ² and R ³ are each independently a hydrogen atom, a lower alkyl group or an acyl group, or either R ² or R ³ And R ¹ together form propane-1,3
Form a diyl group, a 2-hydroxypropane-1,3-diyl group]. 2. The compounding amount of acetylated hyaluronic acid is 0.0001 to 10.0% by weight based on the total amount of the external preparation for skin, and the compounding amount of the compound represented by the formula (I) is 0.001% by weight.
The external preparation for skin according to claim 1, which is about 10.0% by weight.