JPH10279421A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation excellent in percutaneous absorbability of L-ascorbic acid (derivative), low in skin irritancy and high in safety, by including L-ascorbic acid (derivative) and a specific acetylated hyaluronic acid in specified proportions. SOLUTION: This preparation is obtained by formulating (A) 0.01-20 wt.% of L-ascorbic acid (derivative) (e.g. DL-α-tocopherol-2-L-ascorbic phosphoric diester), (B) 0.0001-3.0 wt.% of an acetylated hyaluronic acid so as to be (100:1) to (1:5,000) 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 of 2-4, and (C) as necessary, polyhydric alcohol, oil, organic acid, alkali, surfactant, medicinal agent, ultraviolet light absorber, chelating agent, 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. That is, 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 transdermal absorption enhancers are used, sufficient transdermal absorbability of the drug may not be obtained, and L is used as a whitening agent.
Few transdermal absorption enhancers have been found to be effective against hydrophilic drugs such as ascorbic acid and its derivatives. 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 developed a transdermal absorption enhancer which is excellent in the effect of promoting transdermal absorption of L-ascorbic acid and its derivatives, and which is excellent in safety. As a result of intensive research, by using acetylated hyaluronic acid as a transdermal absorption enhancer,
The present inventors have found that excellent transdermal absorbability of L-ascorbic acid and its derivatives is obtained, and that the skin irritation is low and the safety is excellent, and the present invention has been completed.

That is, according to the present invention, there is provided an acetylated hyaluronic acid having from 0.01 to 20% by weight of L-ascorbic acid and a derivative thereof and an acetylated hyaluronic acid having from 2 to 4 acetyl groups per hyaluronic acid constituent unit. % By weight, and the compounding weight ratio of acetylated hyaluronic acid to L-ascorbic acid and its derivatives is from 100/1 to 1/500.
0 is an external preparation for skin characterized by being 0. Examples of L-ascorbic acid and its derivatives whose transdermal absorption can be increased by the transdermal absorption enhancer of the present invention include the following.

[0007] L-ascorbic acid derivatives include L-ascorbic acid derivatives.
Ascorbic acid alkyl ester, L-ascorbic acid phosphate ester, L-ascorbic acid sulfate ester and the like are mentioned, and specific examples are L-ascorbyl palmitate, L-ascorbyl isopalmitate, L-ascorbyl dipalmitate, L-ascorbyl isopalmitate, L-ascorbyl stearate, L-ascorbyl isostearate, L-ascorbyl distearate, L-ascorbyl diisostearate, L-ascorbyl myristate, L-ascorbyl isomyristate, L-ascorbyl dimyristate L-ascorbyl diisomyristate, L-ascorbyl 2-ethylhexanoate, L-ascorbyl di-2-ethylhexanoate,
L-ascorbic acid alkyl ethers such as L-ascorbyl oleate and L-ascorbyl dioleate;
L-ascorbic acid phosphates such as ascorbic acid-2-phosphate, L-ascorbic acid-3-phosphate, DL-α-tocophenol-2-L-ascorbic acid phosphate, L-ascorbic acid -2
-Sulfate, L-ascorbic acid sulfate such as L-ascorbic acid-3-sulfate, and the like. In the present invention, these salts can also be used, and alkali metal salts such as sodium salts and potassium salts,
Alkaline earth metal salts such as calcium salts and magnesium salts are preferably used. The above-mentioned L-ascorbic acid or a derivative thereof is mainly obtained by a known synthetic method, but it is needless to say that L-ascorbic acid or a derivative thereof can also be used by other methods.
Can be used.

[0008] The above-mentioned L-ascorbic acid and its derivatives and acetylated hyaluronic acid are used by being blended 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.

In this case, the amount of each component varies depending on the type of L-ascorbic acid and its derivatives, the type of dosage form, the method of administration, the purpose of administration and the like, and cannot be unconditionally determined. Generally, the following ranges are preferable compounding amounts. That is, the compounding amount of L-ascorbic acid and its derivative is 0.01 to 20% by weight, more preferably 0.01 to 10% by weight in the external preparation. If the amount is less than 0.01% by weight, the effect of L-ascorbic acid and its derivatives may not be obtained, and if it exceeds 10% by weight, the effect of the drug cannot be expected to be improved. May be inferior.

The molecular weight of the acetylated hyaluronic acid used in the present invention is preferably 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 feeling of use may be deteriorated, 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 added, the amount of the acetylated hyaluronic acid is 0.00
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 may not be exhibited. If the amount is more than 10% by weight, the effect of the drug cannot be expected to be improved, and further, stickiness may be caused in terms of usability, which is not preferable. .

The weight ratio of acetylated hyaluronic acid to L-ascorbic acid and its derivatives in the external preparation for skin according to the present invention is preferably 100/1 to 1/5000.
If the ratio is out of this range, a sufficient effect of the drug may not be obtained, or an L-ascorbic acid derivative or acetylated hyaluronic acid may be added more than necessary, resulting in a disadvantage in cost. That is, even if acetylated hyaluronic acid is added in an amount of more than 100/1, a remarkable improvement in the effect of the drug may not be expected, resulting in a disadvantage in cost. Also, 1 /
Even if more than 5000 L-ascorbic acid and its derivatives are blended, a significant improvement in whitening effect cannot be expected, resulting in 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.

[0015]

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 thereto. 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 an external preparation for skin containing L-ascorbic acid or a derivative thereof 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.

[0017]

[Table 1] Composition (Liquid) Example 1 Comparative Example 1 ──────────────────────── (1) L-ascorbic acid sulfate disodium disodium 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: Acetylation degree 3.5 -Preparation method- (1) and (2) were dissolved in (3) to obtain a sample (Example) 1). (1), (4), and (5) were emulsified in (3) to obtain a sample (Comparative Example 1).

<Drug Permeability Test> Using Example 1 and Comparative Example 1, a skin permeability test of an L-ascorbic acid derivative was performed. -Test method- In order to evaluate the effect of promoting percutaneous absorption on L-ascorbic acid derivatives, 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. 10mm diameter
50 μl of the drug sample was applied to the surface of the membrane, and kept at 37 ° C. in a CO ₂ incubator. After 24 hours, the culture solution was sampled, and the amount of the L-ascorbic acid derivative permeated through the membrane was quantified by high performance liquid chromatography. The results are shown in Table 2 as the drug permeability (%).

[0019]

[Table 2] 薬 剤 Drug permeability (%) ──── << Example 1 13.36 Comparative Example 1 5.38 >> ──────────────────────────────

As is evident from the results in Table 2, the liquid preparation containing the L-ascorbic acid derivative and acetylated hyaluronic acid (Example 1) was used as an L-ascorbic acid derivative and a conventional transdermal external agent absorption enhancer. Compared to the liquid formulation containing isopropyl myristate (Comparative Example 1), the L-ascorbic acid derivative has an excellent skin permeation promoting effect, and the effect is greatly increased by combining acetylated hyaluronic acid. You can see that there is.

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 used as Test Examples 1 to 3. Further, a skin permeability test of the L-ascorbic acid derivative was performed according to Example 1, and the transmittance of the drug (L-ascorbic acid derivative) was also shown in Table 3.

[0022]

[Table 3] ──────────────────────────────────── Composition (solution) Test example No. 1 2 3 ──────────────────────────────────── (1) Disodium L-ascorbic acid sulfate 1.0 1.0 1.0 (2) Acetylated hyaluronic acid 0.5--(3) Purified water Residue Residual Residue (4) Hyaluronic acid--0.5 ──────────────────────── ──────────── Drug permeability (%) 13.36 0.25 0.53 ───────────────────────────── ───────

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

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. Also, L-
The skin permeability test of the ascorbic acid derivative was performed according to Example 1, and the permeability of the drug was shown in Table 4 together.

[0025]

[Table 4] Composition (Liquid) Test example No. 4 5 6 7 ─────────────────────────── (1) Disodium L-ascorbic acid sulfate 1.0 1.0 1.0 1.0 (2) Acetylated acetyl hyaluronate Degree of acetylation 1 0.5 Degree of acetylation 1.5 0.5 Degree of acetylation 2 0.5 Degree of acetylation 4 0.5 (3) Purified water Residue Residue Residue ──────────────────────薬 剤 Drug permeability (%) 1.86 3.29 11.38 14.75 ───────────────────────────────

As is clear 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 prepared with acetylated hyaluronic acid having an acetylation degree of 2 or more. It can be seen that there is no remarkable transdermal absorption effect of the L-ascorbic acid derivative as compared with the liquid preparations (Test Examples 6 and 7).

Amounts of acetylated hyaluronic acid [Test Examples 8 to 13] Liquid preparations having various compositions shown in Table 5 with different amounts of acetylated hyaluronic acid were prepared in accordance with Example 1, and Test Examples 8 to 13 were prepared. 13. Further, a skin permeability test of the L-ascorbic acid derivative was performed in accordance with Example 1, and the results are shown in Table 5.

[0028]

[Table 5] ──────────────────────────────────── Composition (solution) Test example No. 8 9 10 11 12 13 (1) Disodium L-ascorbic acid sulfate 1.0 1.0 1.0 1.0 1.0 1.0 (2) Acetylated hyaluronic acid ^{* 1} 0.00005 0.0001 0.001 5 10 15 (3) Purified water Residue Residue Residue Residue Residue ──────────────────薬 剤 Drug permeability (%) 2.53 10.86 11.34 14.97 15.86 14.85 ──────────────────── ────────────────

As is clear from the results in Table 5, in the liquid preparation containing less than 0.0001% by weight of acetylated hyaluronic acid (Test Example 8), the amount of acetylated hyaluronic acid was 0.0001% by weight or more. Of liquid (Test Examples 9 to 13)
It can be seen that a remarkable transdermal absorption effect of the L-ascorbic acid derivative is not obtained as compared with In addition, a liquid preparation containing 10% by weight or more of acetylated hyaluronic acid (Test Example 1)
3) shows that there is no improvement in the drug permeability as compared with the liquid preparation containing 10% by weight (Test Example 12).

Next, the present inventors examined the whitening effect when a skin external preparation containing L-ascorbic acid and its derivative and acetylated hyaluronic acid was actually used.

Skin lightening 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.

[0032]

Table 6 Composition (emulsion) Example 2 Comparative Example 2 Comparative Example 3 A. DL-α-tocopherol- 2-L-ascorbic acid phosphate diester 8.0 8.0- acetylated hyaluronic acid ^{* 2} 0.01-0.01 ethanol 5.0 5.0 5.0 purified water qs Amount appropriate amount 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 3.8

-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 the L-ascorbic acid derivative was removed from Example 2 were applied to subjects suffering from spots, freckles, etc. And examined its whitening effect. Subjects consisted of a group of 20 women in their 30s and 50s, and administered one emulsion twice a day for 3 months, about 0.5 times each time.
g was applied to the face, and at the end of the period, the whitening effect was determined by interviewing the subject. In the judgment, a score was given according to the following criteria and expressed as an average score. Table 7 shows the results. [Judgment score for whitening effect] 4: Stain, freckles almost inconspicuous 2: Very thin 1: Slightly thin 0: No change

[0035]

[Table 7]

As is clear from the results in Table 7, the emulsion containing only the L-ascorbic acid derivative (Comparative Example 2)
A slight whitening effect can be observed as compared with the emulsion containing no L-ascorbic acid derivative (Comparative Example 3).
However, the emulsion containing the L-ascorbic acid derivative and the acetylated hyaluronic acid (Example 2) has a more remarkable whitening effect as compared with the emulsion containing only the L-ascorbic acid derivative (Comparative Example 2).

Distribution of L-ascorbic acid and its derivatives
Total Amounts [Test Examples 14 to 19] Emulsions of various compositions having different amounts of the L-ascorbic acid derivatives shown in Table 8 were prepared in accordance with Example 2 and used as Test Examples 14 to 19. Further, a test of the whitening effect was performed in accordance with Example 2, and the evaluation was shown in Table 8.

[0038]

[Table 8] Composition (emulsion) Test example No. 14 15 16 17 18 19 ──────────────────────────────────── A. DL-α-Tocopherol-2- L -Ascorbic acid phosphoric acid phosphate 0.005 0.01 0.1 10.0 20.0 25.0 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 qq. 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 C. Carbo Cyvinyl 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 Remaining Quantity ス コ ア Whitening effect score 1.2 2.0 2.2 2.8 3.1 3.0 ─── ─────────────────────────────────

As is clear from the results in Table 8, the emulsions containing 0.01 to 20% by weight of the L-ascorbic acid derivative (Test Examples 15 to 18) are excellent in whitening effect. In contrast, an emulsion containing less than 0.01% by weight of the L-ascorbic acid derivative (Test Example 14)
Has an extremely inferior whitening effect, and the emulsion formulated in excess of 20% by weight (Test Example 19) has no significant improvement of the drug as compared with the emulsion formulated in 20% by weight (Test Example 18). I understand.

Acetylated hyaluronic acid and L-ascorbi
Combination weight ratios of acid and derivatives thereof [Test Examples 20 to 25] Emulsions of various compositions were prepared according to Example 2 in which the mixture weight ratio of acetylated hyaluronic acid and L-ascorbic acid derivative shown in Table 9 was changed. And Test Example 20
To 25. In addition, a test of the whitening effect was performed according to Example 2, and the evaluations are shown in Table 9.

[0041]

[Table 9] Composition (emulsion) Test example No. 20 21 22 23 24 25 ──────────────────────────────────── A. DL-α-Tocopherol-2- L -Ascorbic acid phosphate ester 0.05 0.05 0.05 0.5 5.0 10.0 Acetylated hyaluronic acid ^{* 2} 10.0 5.0 0.5 0.001 0.001 0.001 Ethanol 5.0 5.0 5.0 5.0 5.0 5.0 Purified water qs qs qq qq qs qs B. petrolatum 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 Appropriate amount C. Carboki Cyvinyl 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 Amount ──────────────────────────────────── Compounding weight ratio (AcHA: AsAD) 200/1 100 / 1 10/1 1/500 1/5000 1/10000 ──────────────────────────────────── Whitening Effect score 2.5 2.5 2.3 2.3 2.8 2.7 ────────────────────────────────────

As is clear from the results in Table 9, the emulsion having a compounding weight ratio of acetylated hyaluronic acid and the L-ascorbic acid derivative of 100/1 (Test Example 21) was a 10/1 emulsion (Test Example 22). The whitening effect is improved as compared to On the other hand, an emulsion (Test Example 20) in which the ratio of acetylated hyaluronic acid was increased by more than 100/1 was 100%
No improvement in the whitening effect was observed as compared with the milky lotion (Test Example 21). In addition, 1/5000 emulsion (Test Example 2)
4) shows an improvement in whitening effect as compared with a 1/500 emulsion (Test Example 23). On the other hand, the emulsion (Test Example 25) in which the ratio of the L-ascorbic acid derivative was increased by more than 1/5000 was 1/5000 emulsion (Test Example 24).
No improvement in whitening effect is observed as compared to Therefore, the compounding weight ratio of acetylated hyaluronic acid to L-ascorbic acid and its derivatives is 100/1 to 1/500.
It turns out that 0 is suitable.

Next, in order to make the external preparation for skin of the present invention more specific, examples will be further shown. In addition, the blending amount is%
Is shown. The skin external preparations of these examples exhibited excellent whitening effects as in Example 2.

Example 3 Cream Composition Compounding Amount (%) Stearic acid 1.4 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 L-Ascorbic acid-2-sulfate 1.0 Acetylated hyaluronic acid (acetylation degree 3.3) 2.0 Purified water residue -Preparation method- Component of B Is heated and dissolved at 70 ° C., and the component A is heated and dissolved at 70 ° C., and the mixture is emulsified with a homomixer. After emulsification, the mixture is cooled with a heat exchange device to obtain a cream.

Example 4 Toner Composition Composition Amount (%) L-ascorbyl isostearate 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 β-cyclodextrin 1.0 glycerin 5.0 dipropylene 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.

[0046]

EFFECT OF THE INVENTION The external preparation for skin according to the present invention is excellent in the effect of promoting transdermal absorption of L-ascorbic acid and its derivatives,
It is an external preparation for skin with excellent safety.

Claims (1)

[Claims] 1. An acetylated hyaluronic acid having 0.01 to 20% by weight of L-ascorbic acid and a derivative thereof, and 0.0001 to 10% by weight of an acetylated hyaluronic acid having 2 to 4 acetyl groups per hyaluronic acid structural unit. And a compounding weight ratio of acetylated hyaluronic acid to L-ascorbic acid and its derivatives of from 100/1 to 1/5000.