JPH10279422A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation excellent in percutaneous absorbability of hydroquinone glycoside, low in skin irritancy and high in safety, by including a hydroquinone glycoside and a specific acetylated hyaluronic acid in specified proportions. SOLUTION: This preparation is obtained by formulating (A) 0.01-20 wt.% of a hydroquinone glycoside of the formula (R<6> is a pentose residue, hexose residue, amino acid residue, uronic acid residue, methyl compound thereof or acetyl compound thereof) (e.g. arbutin), (B) 0.0001-10 wt.% of an acetylated hyaluronic acid so as to be (10:1) to (1:10,000) in the weight ratio B/A, pref. with a molecular weight of 10,000-1000,000 in terms of hyaluronic acid and the number of substitution of acetyl groups per hyaluronic acid constitutive unit, and (C) as necessary, polyhydric alcohol, oil, organic acid, alkali, surfactant, medicinal agent, ultraviolet light absorber, antioxidant, antiseptic, thickening agent, moisturizer, perfume, alcohol, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin, and more particularly to an improvement in transdermal absorption of a drug.

[0002]

2. Description of the Related Art Conventionally, as a drug administration method, an external preparation by transdermal administration has been developed. However, in such external preparations, transdermal absorbability of the drug is often not sufficiently obtained, and the purpose is rarely achieved. In other words, the outermost layer of the skin is called the stratum corneum of the skin and originally has a physiological function as a barrier to prevent invasion of foreign substances from outside the body. In many cases, sufficient percutaneous absorbability cannot be obtained simply by blending.

[0003] In order to improve this, in recent years, various percutaneous absorption enhancers have been generally incorporated into the base of external preparations. Such transdermal absorption enhancers include dimethylformamide, dimethylsulfoxide, dimethylacetamide, 1-dodecylazacycloheptan-2-one,
Isopropyl myristate and the like are known.

[0004]

However, even if these percutaneous absorption enhancers are used, sufficient percutaneous absorption of the drug may not be obtained, and in particular, such as hydroquinone glycoside used as a whitening agent. Few transdermal absorption enhancers have been found to be effective for hydrophilic drugs. In addition, many of the above-mentioned percutaneous absorption enhancers are highly irritating to the skin, and by applying a formulation containing the same, a percutaneous absorption enhancer which is satisfactory in terms of safety such as causing erythema on the skin is obtained. It is not currently done.

[0005]

DISCLOSURE OF THE INVENTION In view of the above problems, the present inventors have intensively studied to develop a transdermal absorption enhancer having excellent transdermal absorption promoting effect on hydroquinone glycoside and excellent safety. As a result, it was found that by using acetylated hyaluronic acid as a transdermal absorption enhancer, excellent transdermal absorbability of hydroquinone glycoside was obtained, and skin irritation was low and excellent in safety. Thus, the present invention has been completed.

That is, the present invention relates to a hydroquinone glycoside comprising 0.01 to 20% by weight, and 0.0001 to 10% by weight of acetylated hyaluronic acid having 2 to 4 acetyl groups per hyaluronic acid structural unit. And a compounding weight ratio of acetylated hyaluronic acid to hydroquinone glycoside of from 10/1 to 1/10000.

In the external preparation for skin according to the present invention, the hydroquinone glycoside is preferably arbutin. The following are examples of hydroquinone glycosides whose transdermal absorption can be increased by the transdermal absorption enhancer of the present invention. The hydroquinone glycoside is represented by the following general formula.

[0008]

Embedded image [In formula 1, R ₆ represents a pentose residue, a hexose residue, an amino sugar residue, a uronic acid residue or a methyl compound or an acetyl compound thereof. ]

In the formula, R ₆ is a pentose residue such as L-arabinose, D-xylose, D-ribose, D-xylulose, D-lixose, D-ribulose, D-glucose, D-galactose, D-galactose. Hexacarbon sugar residues such as mannose, D-tagatose, D-fructose, L-sorbose, D-tagatose and D-psicose; amino sugar residues such as D-glucosamine, D-galactosamine, sialic acid and muramic acid; -Glucuronic acid, D-galacturonic acid,
D-mannuronic acid, uronic acid residues such as L-iduronic acid or their methyl compounds and acetyl compounds,
From the viewpoints of pharmacological effect, stability and safety, R ₆ is most preferably D-glucose in which β-glycoside is bound, that is, hydroquinone-β-D-glucoside (generic name: arbutin, hereinafter referred to as arbutin). These drugs are
When mixed with the percutaneous absorption enhancer of the present invention and applied to the skin, it is rapidly absorbed by the skin. If the drug is intended for local action, it will penetrate deeply into the skin and exhibit excellent effects.

The above-mentioned hydroquinone glycoside and acetylated hyaluronic acid are used by being mixed in a suitable external preparation for skin. As the dosage form of the external preparation for skin, cream preparation, ointment preparation, gel preparation, lotion preparation, emulsion, tape preparation, cataplasm preparation, aerosol preparation and the like are used.

[0011] In this case, the amount of each component varies depending on the type of hydroquinone glycoside, the type of dosage form, the method of administration, the purpose of administration and the like, and cannot be determined unconditionally. The range is a preferable compounding amount. That is, the compounding amount of the hydroquinone glycoside is 0.0% in the external preparation.
1 to 20% by weight, more preferably 0.1 to 10% by weight
It is. If the amount is less than 0.01% by weight, the effect of the hydroquinone glycoside may not be sufficiently obtained, and even if the amount is more than 10% by weight, a remarkable improvement in the effect of the drug cannot be expected. May result in cost disadvantages. Further, it is not preferable because the usability may be inferior.

The acetylated hyaluronic acid used in the present invention preferably has a molecular weight of about 10,000 to 1,000,000 in terms of hyaluronic acid. The acetylated hyaluronic acid used in the present invention preferably has 2 to 4 acetyl groups per structural unit of the acetylated hyaluronic acid. When the number of substitution of the acetyl group is less than 2, the effect as a transdermal absorption enhancer may be weak, and when the number of substitution of the acetyl group is more than 4, it is difficult in the production method.

The method for producing the acetylated hyaluronic acid according to the present invention is as follows. A method in which powdery hyaluronic acid is dispersed in acetic acid and reacted by adding trifluoroacetic anhydride as a catalyst, or a method in which it is dispersed in acetic acid, p-toluenesulfonic acid is added, and acetic anhydride is further added, and the reaction is performed. A method of suspending and reacting by adding concentrated sulfuric acid is known (JP-A-6-9707, JP-A-8-5350).
1).

In the present invention, when acetylated hyaluronic acid is compounded, the compounding amount is 0.00% of the total amount of the external preparation for skin.
It is from 0.01 to 10% by weight, preferably from 0.001 to 5% by weight. If the amount is less than 0.0001% by weight, the effect as a percutaneous absorption enhancer may not be exhibited. Even if the amount exceeds 10% by weight, a remarkable improvement in the effect of the drug cannot be expected, and the cost is disadvantageous. May occur. Furthermore, stickiness may occur in the usability, which is not preferable.

The compounding weight ratio of acetylated hyaluronic acid to hydroquinone glycoside in the external preparation for skin according to the present invention is 1
0/1 to 1/10000 are preferred. If the ratio is out of this range, sufficient effect of the drug may not be obtained, or hydroquinone glycoside or acetylated hyaluronic acid may be added more than necessary, which may cause a disadvantage in cost. That is, even if acetylated hyaluronic acid is added in an amount of more than 10/1, a remarkable improvement in the effect of the drug may not be expected, resulting in cost disadvantage. Further, even if more than 1 / 10,000 of hydroquinone glycoside is blended, remarkable improvement of the whitening effect cannot be expected, so that there may be a disadvantage in cost. Further, if the optimum ratio is not satisfied, the usability may be significantly deteriorated in some cases, which is not preferable.

In the external preparation for skin according to the present invention, in addition to the above-mentioned essential components, components generally used for pharmaceuticals, quasi-drugs, cosmetics and the like can be added. As those components, glycerin, propylene glycol,
Polyhydric alcohols such as 1,3-butanediol, liquid paraffin, squalane, higher alcohols, oils such as higher fatty acids, citric acid, organic acids such as lactic acid, caustic potash,
Alkalis such as triethanolamine, anionic surfactants such as higher alkyl sulfates and higher alkyl ether sulfates; cationic surfactants such as higher alkyl quaternary ammonium salts and alkylpyridinium salts; higher alkyl dimethylamines Amphoteric surfactants such as oxides, nonionic surfactants such as polyoxyethylene alkyl ethers, sorbitan fatty acid esters and polyglycerin fatty acid esters, drugs such as ascorbic acid derivatives and tocopherol derivatives, ultraviolet absorbers, chelating agents, and antioxidants Agents, preservatives, thickeners, humectants, fragrances, alcohols and the like.

[0017]

The present invention will be described in more detail with reference to the following examples, comparative examples and test examples, but the present invention is not limited to these examples. In addition, all the compounding amounts shown below are% by weight. The acetylation degree indicates the number of acetyl groups substituted per hyaluronic acid constituent unit of acetylated hyaluronic acid. First, the present inventors conducted the following tests in the process of examining a skin external preparation containing a hydroquinone glycoside and a transdermal absorption enhancer.

Comparison between the present invention and the prior art [Example 1 and Comparative Example 1] Liquid preparations having the compositions shown in Table 1 were prepared and used as Example 1 and Comparative Example 1.

[0019]

[Table 1] Composition (Liquid) Example 1 Comparative Example 1 ────────────────────── (1) arbutin 1.0 1.0 (2) acetylated hyaluronic acid ^{* 1} 0.5-(3) purified water Residue Residue (4) Isopropyl myristate -0.5 (5) POE (60) hydrogenated castor oil-1.0 ────────────────────── ─────── * 1: Degree of acetylation 3.7 -Preparation method- (1) and (2) were dissolved in (3) to prepare a sample (Example 1). (1), (4), and (5) were emulsified in (3) to obtain a sample (Comparative Example 1).

<Skin Permeability Test of Drug> Using Example 1 and Comparative Example 1, a skin permeability test of hydroquinone glycoside was carried out. -Test method- In order to evaluate the effect of promoting percutaneous absorption on hydroquinone glycosides, a skin penetration test was performed in vitro using model skin. For the model skin, a differentiated epidermal cell membrane obtained by culturing human epidermal cells on a collagen-treated nylon membrane and causing proliferation and differentiation was used. 50 μl of the drug sample was applied to the surface of a 10 mm-diameter membrane, and kept at 37 ° C. in a CO ₂ incubator. After 24 hours, the culture was sampled, and the amount of hydroquinone glycoside permeated through the membrane was determined by high performance liquid chromatography. The results were expressed as drug permeability (%). Table 2 shows the results.

[0021]

[Table 2] As is clear from the results in Table 2, a liquid formulation containing a hydroquinone glycoside and acetylated hyaluronic acid (Example 1)
Is superior to the liquid preparation containing hydroquinone glycoside and isopropyl myristate, which has been conventionally used as a transdermal absorption enhancer (Comparative Example 1), in that the skin permeation promoting effect of hydroquinone glycoside is superior, and acetylated hyaluronic acid It can be seen that the effect is greatly increased by combining the acids.

Formulation of acetylated hyaluronic acid [Test Examples 1 to 3] Liquid preparations having various compositions shown in Table 3 were prepared in accordance with Example 1 and referred to as Test Examples 1 to 3. The skin permeability test of the hydroquinone glycoside was performed according to Example 1, and the transmittance of the drug (hydroquinone glycoside) was also shown in Table 3.

[0023]

[Table 3] ──────────────────────────────────── Composition (solution) Test example No. 1 2 3 ──────────────────────────────────── (1) Arbutin 1.0 1.0 1.0 (2) Acetylated hyaluronic acid ^{* 1} 0.5--(3) Purified water Residue Residue Residue (4) Hyaluronic acid--0.5 ─────────────────────────────薬 剤 Drug permeability (%) 11.99 0.10 0.25 ────────────────────────────────── ──

As is clear from the results in Table 3, the liquid formulation containing acetylated hyaluronic acid (Test Example 1) is superior to the liquid formulation containing no transdermal absorption enhancer (Test Example 2). Percutaneous absorption of hydroquinone glycoside. In addition, the liquid preparation containing normal hyaluronic acid (Test Example 3) did not show a remarkable transdermal absorption effect of hydroquinone glycoside.

Acetylation degree of acetylated hyaluronic acid [Test Examples 4 to 7] Liquid preparations of various compositions containing acetylated hyaluronic acid having different acetylation degrees shown in Table 4 were prepared in accordance with Example 1, and tested. Examples 4 to 7 were used. Further, skin permeability test of the hydroquinone glycoside was carried out according to Example 1, and the permeability of the drug was shown in Table 4 together.

[0026]

[Table 4] ──────────────────────────────────── Composition (solution) Test example No. 4 5 6 7──────────────────────────────────── (1) Arbutin 1.0 1.0 1.0 1.0 (2) Degree of acetylation of acetylated hyaluronic acid 10.5 Degree of acetylation 1.5 0.5 Degree of acetylation 20.5 Degree of acetylation 40.5 (3) Purified water Remaining Remaining Remaining Remainder ──────────────────────────────────── Drug permeability (%) 3.57 4.38 10.75 12.87 ─ ───────────────────────────────────

As is evident from the results in Table 4, the liquid preparations containing acetylated hyaluronic acid having a degree of acetylation of less than 2 (Test Examples 4 and 5) were formulated with acetylated hyaluronic acid having an acetylation degree of 2 or more. It can be seen that the hydroquinone glycoside has no remarkable transdermal absorption effect as compared with the liquid preparations (Test Examples 6 and 7).

The amount of acetylated hyaluronic acid and the amount of drug
Transmittance [Test Examples 8 to 11] Liquid preparations of various compositions having different amounts of acetylated hyaluronic acid shown in Table 5 were prepared in accordance with Example 1 to obtain Test Examples 8 to 11. The skin permeability test of the hydroquinone glycoside was carried out in accordance with Example 1, and the permeability of the drug was shown in Table 5 together.

[0029]

[Table 5] ──────────────────────────────────── Composition (solution) Test example No. 8 9 10 11 12 13 ──────────────────────────────────── (1) Arbutin 1.0 1.0 1.0 1.0 1.0 1.0 ( 2) Acetylated hyaluronic acid ^{* 1} 0.00005 0.0001 0.001 5.0 10 15 (3) Purified water residue residue residue residue residue residue ─────────────────────────薬 剤 Drug permeability (%) 3.49 8.73 10.97 18.26 17.53 18.02 ─────────────────────────── ─────────

As is evident from the results in Table 5, the liquid preparation containing less than 0.0001 of the acetylated hyaluronic acid (Test Example 8) is the liquid preparation containing 0.001 or more of the acetylated hyaluronic acid (Test Example 8). Compared with Examples 9 to 13), it can be seen that a remarkable transdermal absorption effect of hydroquinone glycoside is not obtained. In addition, a liquid formulation containing more than 10% by weight of acetylated hyaluronic acid (Test Example 1)
In 3), it can be seen that remarkable improvement in the drug permeability cannot be expected as compared with the liquid preparation (Test Example 12) in which 10% by weight is blended. Therefore, it is understood that the blending amount of acetylated hyaluronic acid is preferably 0.0001 to 10% by weight.

Next, the present inventors examined the whitening effect and the usability when a skin external preparation containing a hydroquinone glycoside and acetylated hyaluronic acid was actually used.

Skin whitening effect of the external preparation for skin of the present invention [Example 2 and Comparative Examples 2 and 3] Emulsions having the compositions shown in Table 6 were prepared and used as Examples 2 and Comparative Examples 2 and 3.

[0033]

Table 6 Composition (emulsion) Example 2 Comparative Example 2 Comparative Example 3 A. Arbutin 8.0 8.0- acetylated hyaluronic acid ^{* 2} 0.01-0.01 ethanol 5.0 5.0 5.0 purified water qs qs B. Vaseline 1.5 1.5 1.5 Squalane 1.0 1.0 1.0 Liquid paraffin 5.0 5.0 5.0 Cetanol 0.5 0.5 0.5 POE (25) cetyl ether 2.0 2.0 2.0 Glyceryl monostearate 2.0 2.0 2.0 Methyl parahydroxybenzoate 0.15 0.15 0.15 Fragrance Suitable amount Suitable amount Suitable amount C.I. Carboxyvinyl polymer 0.2 0.2 0.2 Caustic potash 0.07 0.07 0.07 Dipropylene glycol 5.0 5.0 5.0 Sorbit solution (70%) 5.0 5.0 5.0 Purification Water residue residue residue residue ──────────────────────────────────── * 2: Degree of acetylation 3.4

-Preparation Method- The component C is heated and dissolved at 70 ° C, the component B is heated and dissolved at 70 ° C, and the mixture is emulsified with a homomixer. After the emulsification, the mixture is cooled to 30 ° C. while stirring, and a solution in which the component A is dissolved is added and mixed uniformly.

<Whitening Effect Test> All three emulsions of Example 2, Comparative Example 2 and Comparative Example 3 except that hydroquinone glycoside was removed from Example 2 were applied to subjects suffering from spots, freckles, etc. , And examined its whitening effect. The subjects were women in their 30s and 50s as 20 groups,
One emulsion was applied to the face twice a day twice a day for 3 months, and at the end of the period, the whitening effect was determined by interviewing the subject. In the judgment, a score is given according to the following criteria, and the results are shown in Table 7 as an average score. [Judgment score for whitening effect] 4 Spots and freckles were almost inconspicuous 2 Very thin 1 Slightly thin 0 No change

[0036]

[Table 7]

As is clear from the results in Table 7, the emulsion containing only the hydroquinone glycoside (Comparative Example 2) shows a slight whitening effect as compared with the emulsion containing no hydroquinone glycoside (Comparative Example 4). be able to. However, it can be seen that the emulsion containing the hydroquinone glycoside and the acetylated hyaluronic acid (Example 2) has a more remarkable whitening effect as compared with the emulsion containing only the hydroquinone glycoside (Comparative Example 2). .

Hydroquinone Glycoside Content and Whitening Effect [Test Examples 14 to 19] Emulsions of various compositions having different hydroquinone glycoside content shown in Table 8 were prepared according to Example 2 and tested. Examples 14 to 19 were used. Further, a test of the whitening effect was performed in accordance with Example 2, and the evaluation was shown in Table 8.

[0039]

[Table 8] Composition (emulsion) Test example No. 14 15 16 17 18 19 A. Arbutin 0.005 0.01 0.1 10 20 25 Acetylated hyaluronic acid ^{* 2} 0.01 0.01 0.01 0.01 0.01 0.01 Ethanol 5.0 5.0 5.0 5.0 5.0 5.0 Purified water qs qq qq qq qq. Vaseline 1.5 1.5 1.5 1.5 1.5 1.5 Squalane 1.0 1.0 1.0 1.0 1.0 1.0 Liquid paraffin 5.0 5.0 5.0 5.0 5.0 5.0 Cetanol 0.5 0.5 0.5 0.5 0.5 0.5 POE (25) cetyl ether 2.0 2.0 2.0 2.0 2.0 2.0 Glyceryl monostearate 2.0 2.0 2.0 2.0 2.0 2.0 Methyl paraoxybenzoate 0.15 0.15 0.15 0.15 0.15 0.15 Fragrance Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Carboxyvinyl polymer 0.2 0.2 0.2 0.2 0.2 0.2 Caustic potash 0.07 0.07 0.07 0.07 0.07 0.07 Dipropylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 Sorbit liquid (70%) 5.0 5.0 5.0 5.0 5.0 5.0 Purified water Remaining Remaining Remaining Remaining Quantity ──────────────────────────────────── Whitening effect score 0.8 1.8 2.3 2.9 3.2 3.1 ─── ─────────────────────────────────

As is clear from the results in Table 8, the emulsions containing 0.01% by weight or more of hydroquinone glycoside (Test Examples 15 to 19) have excellent whitening effects. On the other hand, it can be seen that the emulsion containing less than 0.01% by weight of the hydroquinone glycoside (Test Example 14) has extremely poor whitening effect. An emulsion containing more than 20% by weight of hydroquinone glycoside (Test Example 1)
9) shows that there is no remarkable improvement in the whitening effect as compared with the emulsion containing 20% by weight (Test Example 18). Therefore, the blending amount of hydroquinone glycoside is 0.0
It turns out that 1-20 weight% is suitable.

Acetylated hyaluronic acid and hydroquinone
Glycoside blending weight ratios [Test Examples 20 to 25] Liquid preparations of various compositions having different blending weight ratios of acetylated hyaluronic acid (AcHA) and hydroquinone glycoside (HqG) shown in Table 9 were used in Example 2. Prepared in accordance with Test Examples 20 to 25. Further, the test of the whitening effect was performed according to Example 2, and the evaluation was shown in Table 9.

[0042]

[Table 9] 組成 Composition (emulsion) Test Example No. 20 21 22 23 24 25 A. Arbutin 0.1 0.1 0.1 0.2 2.0 20 Aceylated hyaluronic acid ^{* 2} 10 1.0 0.1 0.0002 0.0002 0.0002 Ethanol 5.0 5.0 5.0 5.0 5.0 5.0 Purified water qs qq qq qq qq. Vaseline 1.5 1.5 1.5 1.5 1.5 1.5 Squalane 1.0 1.0 1.0 1.0 1.0 1.0 Liquid paraffin 5.0 5.0 5.0 5.0 5.0 5.0 Cetanol 0.5 0.5 0.5 0.5 0.5 0.5 POE (25) cetyl ether 2.0 2.0 2.0 2.0 2.0 2.0 Glyceryl monostearate 2.0 2.0 2.0 2.0 2.0 2.0 Methyl paraoxybenzoate 0.15 0.15 0.15 0.15 0.15 0.15 Fragrance Appropriate amount Appropriate amount Appropriate amount Appropriate amount Appropriate amount Carboxyvinyl polymer 0.2 0.2 0.2 0.2 0.2 0.2 Caustic potash 0.07 0.07 0.07 0.07 0.07 0.07 Dipropylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 Sorbit solution (70%) 5.0 5.0 5.0 5.0 5.0 5.0 Purified water Remaining Remaining Remaining Remaining Amount ──────────────────────────────────── Compounding weight ratio (AcHA / HqG) 100/1 10 / 1 1/1 1/1000 1/10000 1/100000 ──────────────────────────────────── Whitening Effect 2.5 2.6 2.3 2.6 3.2 2.9 ────────────────────────────────────

As is clear from the results in Table 9, the emulsion having a compounding weight ratio of acetylated hyaluronic acid and hydroquinone glycoside of 10/1 (Test Example 21) was different from the emulsion having a 1/1 weight (Test Example 22). An improvement in the whitening effect is seen in comparison. On the other hand, the milky lotion in which the ratio of acetylated hyaluronic acid was increased by more than 10/1 (Test Example 20) did not show any improvement in whitening effect as compared with the 10/1 emulsion (Test Example 21).
Also, 1/10000 emulsion (Test Example 24) was 1/1
The whitening effect is improved as compared with the milky lotion (Test Example 23). On the other hand, an emulsion in which the ratio of hydroquinone glycoside was increased to more than 1/10000 (Test Example 2)
5) shows no improvement in the whitening effect as compared with a 1 / 10,000 emulsion (Test Example 24). Therefore, it is understood that the weight ratio of acetylated hyaluronic acid to hydroquinone glycoside is preferably from 10/1 to 1/10000.

Next, in order to make the external preparation for skin of the present invention more concrete, examples will be further shown. In addition, the blending amount is%
Is shown. In each of the following examples, as a result of performing a test of the whitening effect according to the example 2, the same excellent whitening effect as the example 2 was shown.

Example 3 Cream Composition Compounding Amount (%) Stearic acid 14.0 Cetanol 3.0 Sorbitan monostearate 2.0 Polyoxyethylene (20) sorbitan monostearate 1.5 Propyl parahydroxybenzoate 0.2 Fragrance Appropriate amount Propylene glycol 8.0 Glycerin 2.0 Caustic potash 0.2 Hydroquinone-N-acetyl-β-D-glucosaminide 1.0 Acetylated hyaluronic acid (acetylation degree 3.3) 2.0 Purified water residue -Preparation method-B Is heated and dissolved at 70 ° C., and the component A is heated and dissolved at 70 ° C., and the mixture is emulsified by a homomixer. After emulsification, the mixture is cooled with a heat exchange device to obtain a cream.

Example 4 Toner Composition Composition Amount (%) Arbutin 3.0 Acetylated hyaluronic acid (degree of acetylation 3.0) 0.2 Citric acid 0.2 Sodium citrate 0.8 Trisodium edetate 0.1 Hydroxypropyl beta cyclodextrin 1.0 Glycerin 5.0 Di Propylene glycol 5.0 Purified water residue B. Ethanol 10.0 POE (60) hydrogenated castor oil 1.0 Methyl parahydroxybenzoate 0.15 Fragrance Appropriate amount-Production method-The alcohol phase of A was added to the aqueous phase of B and solubilized to obtain a lotion.

[0047]

Industrial Applicability The external preparation for skin according to the present invention is an external preparation for skin excellent in the effect of promoting transdermal absorption of hydroquinone glycoside and also excellent in safety.

Claims (2)

[Claims] 1. An acetylated hyaluronic acid having a hydroquinone glycoside content of 0.01 to 20% by weight and an acetyl group substituted with 2 to 4 acetyl groups per hyaluronic acid structural unit 0.000.
1 to 10% by weight, and the compounding weight ratio of acetylated hyaluronic acid to hydroquinone glycoside is 10/1 to 1
/ 10000, a skin external preparation. 2. The external preparation for skin according to claim 1, wherein
An external preparation for skin, wherein the hydroquinone glycoside is arbutin.