JPH10279418A - Preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject preparation capable of markedly raising rough skin preventive and remedying effect by including an acetylated hyaluronic acid and tranexamic acid. SOLUTION: This preparation contains (A) 0.0001-10 wt.% of an acetylated hyaluronic acid 2-4 in the number of substitution of acetyl groups per hyaluronic acid constitutive unit, formed, for example, by dispersing powdery hyaluronic acid in acetic acid followed by reaction in the presence of trifluoroactic anhydride as catalyst and (B) 0.01-10 wt.% of tranexamic acid in the weight ratio A/B of (60:1) to (1:500).

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 the function of preventing rough skin and improving rough skin.

[0002]

2. Description of the Related Art Conventionally, hyaluronic acid has been blended in an external preparation for skin for the purpose of imparting a moisturizing effect, and has also been used to obtain a unique use feeling of a polymer having affinity for skin. On the other hand, tranexamic acid has been conventionally used in pharmaceuticals as an anti-inflammatory agent, and it has recently been found that it has an effect of improving skin roughness.

[0003]

However, the effects of hyaluronic acid or tranexamic acid on the prevention of rough skin and the improvement of the rough skin are not yet sufficient, and the effects cannot be expected. The present invention has been made in view of the above-mentioned problems of the related art, and an object of the present invention is to provide a novel external preparation for skin which has a drastically improved effect of preventing and improving rough skin.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that a skin external preparation containing acetylated hyaluronic acid and tranexamic acid achieves this object. Thus, the present invention has been completed.

That is, the external preparation for skin according to the present invention comprises:
When the number of substitution of acetyl groups per hyaluronic acid structural unit is 2
Acetylated hyaluronic acid of 0.001 to 10
% Of tranexamic acid and 0.01 to 10% by weight of tranexamic acid, and the blending ratio of acetylated hyaluronic acid to tranexamic acid is from 60/1 to 1/5000.

[0006]

Embodiments of the present invention will be described below in detail. 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.

[0007] The acetylated hyaluronic acid used in the present invention preferably has 2 to 4 acetyl groups per hyaluronic acid constituent unit. The effects of the invention may not be sufficiently obtained, and those having more than 4 acetyl groups are difficult to manufacture. The method for producing the acetylated hyaluronic acid used in the present invention is as follows.

A method of dispersing hyaluronic acid in powder form in acetic acid and reacting by adding trifluoroacetic anhydride as a catalyst, a method of dispersing in acetic acid and adding p-toluenesulfonic acid and further adding acetic anhydride and reacting the same, A method of suspending in an acetic acid solvent and adding concentrated sulfuric acid to cause a reaction is known (JP-A-6-9707, JP-A-8-53501).

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 sufficiently exhibited. Even if the amount is more than 10% by weight, it is not possible to expect a significant improvement in the effect of preventing skin roughness and improving skin roughness, and further, it is inferior in usability. Is not preferred.

The amount of tranexamic acid in the present invention is preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight, based on the total amount of the external preparation for skin.
If the blending amount of tranexamic acid is less than 0.01% by weight, the effect of the present invention is hardly obtained, and even if the blending amount exceeds 10% by weight, it is not possible to expect so much improvement in skin roughening prevention and skin roughening effect. It is not preferable because the usability may be inferior.

In the present invention, the compounding weight ratio in which synergistic action of both acetylated hyaluronic acid and tranexamic acid is remarkably recognized is approximately 60/1 to 1 / 5,000 after satisfying the effective compounding amounts of both. . If the ratio is out of this range, one of the agents is added more than necessary, which may cause a disadvantage in cost.

In addition to the above-mentioned essential components, the skin external preparation of the present invention also contains other components usually used in skin external preparations such as cosmetics and pharmaceuticals, such as avocado oil, palm oil, peanut oil, tallow, rice bran oil, jojoba oil. Oil, carnauba wax, lanolin, liquid paraffin, oxystearic acid, oil such as isostearyl palmitate, isostearyl alcohol, glycerin, sorbitol, polyethylene glycol, pyrrolidone carboxylic acid and salts thereof, collagen,
Moisturizers such as hyaluronic acid and its salts, chondroitin sulfate and its salts, ultraviolet absorbers such as amyl paradimethylaminobenzoate, urocanic acid, ethyl diisopropylcinnamate, and antioxidants such as sodium erythorbate, sage extract, and parahydroxyanisole Agent, sodium stearyl sulfate, diethanolamine cetyl sulfate,
Surfactants such as cetyltrimethylammonium saccharin, polyethylene glycol isostearate, and glyceryl arachiate; preservatives such as ethylparaben and butylparaben; extracts such as oak, orange, sicon, peonies, assembly, birch and loquat; Inflammatory agents such as glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin, placenta extracts, glutathione, yukinoshita extracts, ascorbic acid derivatives, etc. , Extract such as lily, royal jelly, photosensitizer, cholesterol derivative, activator such as various amino acids, saffron, senkyu, ginger, hypericum, ononis, rosemary, garlic, etc. Exudates, blood circulation promoters such as γ-oryzanol, dextran sodium sulfate, etc., antiseborrheic agents such as sulfur, thiantol, thickeners such as fragrance, water, alcohol, carboxyvinyl polymer, titanium yellow, carsamine, safflower red, etc. The coloring agent and the like can be appropriately compounded as needed.

The dosage form of the external preparation for skin of the present invention is arbitrary,
Any dosage form, such as a solution type, a solubilizing type, an emulsifying type, a powder dispersing type, a water-oil two-layer system, a water-oil-powder three-layer system, may be used. In addition, the use of the external preparation for skin of the present invention is also optional. Facial cosmetics such as lotions, emulsions, creams, packs and the like, makeup cosmetics such as foundations, lipsticks, eye shadows, etc., body cosmetics, aromatic cosmetics, cleaning Paints, ointments and the like.

[0014]

EXAMPLES Next, the present invention will be specifically described with reference to Examples, Comparative Examples and Test Examples. The present invention is not limited by this. In addition, the compounding amount is 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 studying a skin external preparation containing acetylated hyaluronic acid.

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

<Test of Skin Roughness Improvement Effect> The creams of Example 1 and Comparative Example were subjected to a skin roughness improvement effect test on a human body panel. When choosing a human body panel, a healthy female person (face)
A replica of the skin was taken using a myristin resin replica method, and the skin surface morphology was observed with a microscope (17 ×).
The cream of Example 1 was applied to the left and right half of the face using 20 persons (rough skin panels) determined to have rough skin evaluations 1 and 2 based on the criteria shown in Table 2 based on the state of the skin print and the peeling state of the stratum corneum. The cream of the comparative example was applied twice a day. Two weeks later, a replica was again taken to observe the condition of the skin, and evaluated according to the criteria shown in Table 2. Table 3 shows the evaluation results.

[0017]

[Table 1] Composition (cream) Example 1 Comparative Example ──────────────────────────────────── A. Cetanol 0.5 0.5 Vaseline 2.0 2.0 Squalane 7.0 7.0 Self-emulsifying glyceryl monostearate 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 Punt Tenyl ethyl ether 0.5 0.5 Jojoba oil 5.0 5.0 B. Propylene glycol 5.0 5.0 Glycerin 5.0 5.0 Vegum (montmorillonite) 5.0 5.0 Aceylated hyaluronic acid ^{* 1} 0.1-Hyaluronic acid-0.1 Tranexamic acid 2.0 2.0 Water Residue Residual ──────────────────────────────────── * 1: Degree of acetylation 3 -Production method- A (oil phase) and B (aqueous phase) are each heated to 70 ° C. and completely dissolved. Add A to B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream.

[0018]

[Table 2] ──────────────────────────────────── Evaluation score Remarks ──── １ 1 point Elimination of skin sulcus and skin hills Widespread turning of the stratum corneum Rough skin 2 skin Grooves and skins are unclear ↑ Turn of the horny layer 3 Skin grooves and skins are recognized but flat 4 Skin and skins are clear ↓ 5 Skin and skins are clear and beautiful ───────────────────────────────

[0019]

[Table 3] 評 価 Replica evaluation Example 1 Comparative example ─── ───────────────────────────────── 1 point 0 people 0 people 2 0 4 3 2 10 4 6 6 5 12 0 ──────────────────────────────────── Panel total 20 people 20 people ─────── ─────────────────────────────

As is clear from the results in Table 3, the face portion using the cream containing acetylated hyaluronic acid and tranexamic acid (Example 1) was treated with hyaluronic acid and a skin roughening agent conventionally used as moisturizers. As compared with the facial part using a cream containing tranexamic acid (Comparative Example), which has been used as the above, a remarkable skin roughness improving effect was observed. Therefore, it can be seen that the skin external preparation containing the acetylated hyaluronic acid and tranexamic acid of the present invention is superior to the conventional skin external preparation in the effects of preventing and improving skin roughness.

Formulation of acetylated hyaluronic acid and tranexamic acid [Test Examples 1 to 4] The creams of various formulations shown in Table 4 were subjected to a test for improving skin roughness on a human body panel, and the results are shown in Table 5. The method for producing the cream was the same as in Example 1 and Comparative Example. The test method for improving skin roughness is the same as in Example 1 and Comparative Example, except that the cream of Test Example 1 and one of the creams of Test Examples 2 to 4 are applied to the left and right halves of the face of the 30 panels with rough skin. Was. The evaluation criteria are as shown in Table 2.

[0022]

[Table 4] ──────────────────────────────────── Composition (Cream) Test Example No. 1 2 3 4 A. Cetanol 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 Self-emulsifying glyceryl monostearate 2.5 2.5 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 Hoho oil 5.0 5.0 5.0 5.0 B. Propylene glycol 5.0 5.0 5.0 5.0 Glycerin 5.0 5.0 5.0 5.0 Pericam (montmorillonite) 5.0 5.0 5.0 5.0 Acetylated hyaluronic acid ^{* 1} 0.1 2.1 Tranexamic acid 2.0 2.1 Water Residual Residual Residual ───────────────── ───────────────────

[0023]

[Table 5] レ プ リ カ Replica evaluation test example No. 1 2 3 4 ──────────────────────────────────── 1 point 0 people 7 people 0 people 2 people 2 0 3 5 4 3 3 4 4 4 4 9 0 1 1 0 5 18 0 0 0 ─── Panel total 30 people 10 people 10 people 10 people ────────────────────────────────────

As is clear from the results shown in Table 5, the cream containing acetylated hyaluronic acid and tranexamic acid (Test Example 1) has a remarkable skin roughness improving effect as compared with the other creams (Test Examples 2 to 4). Was observed. On the other hand, the cream containing only tranexamic acid (Test Example 3) or the cream containing only acetylated hyaluronic acid (Test Example 4) was slightly different from the cream containing neither of them (Test Example 2). Although the effect of improving rough skin is recognized, it is still insufficient. Therefore, it can be seen that the combined use of acetylated hyaluronic acid and tranexamic acid synergistically improves the effects of preventing and improving skin roughness.

Acetylation degree of acetylated hyaluronic acid [Test Examples 5 to 8] Creams of various formulas containing acetylated hyaluronic acid having different acetylation degrees shown in Table 6 were subjected to a skin roughness improving effect test on a human body panel. The results are shown in Table 6. The method for producing the cream was the same as in Example 1 and Comparative Example. The test method for improving skin roughness is Example 1
According to the same manner as in the comparative example, the test was carried out by dividing the 20 rough skin panels into two groups and applying the creams of Test Examples 5 and 7 or Test Examples 6 and 8 to the left and right halves of the face, respectively. The evaluation criteria are as shown in Table 2.

[0026]

[Table 6] 組 Composition (Cream) Test Example No. 5 6 7 8 A. Cetanol 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 Self-emulsifying glyceryl monostearate 2.5 2.5 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 Jojoba oil 5.0 5.0 5.0 5.0 B. Propylene glycol 5.0 5.0 5.0 5.0 Glycerin 5.0 5.0 5.0 5.0 Pericam (montmorillonite) 5.0 5.0 5.0 5.0 Acetylation degree of acetylated hyaluronic acid 1 0.1 Degree of acetylation 1.5 0.1 Degree of acetylation 2 0.1 Degree of acetylation 4 0.1 Tranexamic acid 2.0 2.0 2.0 2.0 Water Residue Residue Remaining ──────── ────────────────────────────

[0027]

[Table 7] レ プ リ カ Replica evaluation test example No. 5 6 7 8 ──────────────────────────────────── 10 0 0 0 0 2 5 3 0 0 3 4 5 1 1 1 4 1 2 3 2 5 0 0 6 7 ── Panel total 10 people 10 people 10 people 10 people ────────────────────────────────────

As is clear from the results in Table 7, creams containing acetylated hyaluronic acid having a degree of acetylation of 2 or more (Test Examples 7 and 8) contain acetylated hyaluronic acid having a degree of acetylation of less than 2. A remarkable skin roughness improving effect was observed compared to the cream (Test Examples 5 and 6). Therefore, it is understood that in the external preparation for skin of the present invention, the number of substitutions of the acetyl group of the acetylated hyaluronic acid is preferably 2 to 4 per hyaluronic acid constituent unit.

Formulation of tranexamic acid [Test Examples 9 to 14] Creams of various formulations containing other anti-inflammatory agents instead of tranexamic acid shown in Table 8 were tested on a human body panel for the effect of improving skin roughness. Are shown in Table 9. The method for producing the cream was the same as in Example 1 and Comparative Example. The test method for improving skin roughness is the same as in Example 1 and Comparative Example.
The test was performed by applying the cream of Test Example 9 and one of Test Examples 10 to 14 to the left and right halves of the face, respectively. The evaluation criteria are as shown in Table 2.

[0030]

[Table 8] ──────────────────────────────────── Composition (cream) Test Example No. 9 10 11 12 13 14 A. Cetanol 0.5 0.5 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 7.0 7.0 Self-emulsifying glycerin monostearate 2.5 2.5 2.5 2.5 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 0.5 0.5 Jojoba oil 5.0 5.0 5.0 5.0 5.0 5.0 B. propylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 glycerin 5.0 5.0 5.0 5.0 5.0 5.0 pericamu (montmorillonite) 5.0 5.0 5.0 5.0 5.0 5.0 acetylated hyaluronic acid ^{* 1} 0.1 0.1 0.1 0.1 0.1 0.1 tranexamic acid 2.0 click Bu Richirurichin Sanjikari Beam 2.0 allantoin 2.0 azulene 2.0 ε- aminocaproic acid 2.0 hydrocortisone 2.0 water residual residual residual residual residual residual ────────────────────────────── ──────

[0031]

[Table 9] レ プ リ カ Replica evaluation test example No. 9 10 11 12 13 14 ──────────────────────────────────── 1 point 0 people 0 people 0 people 0 people 0 Name 0 2 0 10 0 2 1 2 3 3 3 3 5 2 2 2 4 8 2 1 2 3 2 5 ... ... ... ... ... ───────────────── Panel total 30 people 6 people 6 people 6 people 6 people ─────────────────── ─────────────────

As is clear from the results in Table 9, the cream containing tranexamic acid (Test Example 9) was compared with the cream containing other anti-inflammatory agents (Test Examples 10 to 14).
A remarkable synergistic effect on the rough skin improving effect is observed.
Therefore, acetylated hyaluronic acid, when combined with tranexamic acid, among the same anti-inflammatory agents,
It can be seen that a synergistic effect of remarkable skin roughness prevention and skin roughness improvement effects occurs.

Amounts of acetylated hyaluronic acid [Test Examples 15 to 20] Creams of various formulas with different amounts of acetylated hyaluronic acid shown in Table 10 were subjected to a rough skin improvement effect test on a human body panel. 11 is shown. The method for producing the cream was the same as in Example 1 and Comparative Example. The test method of skin roughness improvement is the same as that in Example 1 and Comparative Example, except that 30 skin roughness panels are divided into three groups, and two creams of Test Examples 15 to 20 are respectively applied to the left and right halves of the face. Was. The evaluation criteria are as shown in Table 2.

[0034]

[Table 10] ──────────────────────────────────── Composition (Cream) Test Example No. 15 16 17 18 19 20 ──────────────────────────────────── A. Cetanol 0.5 0.5 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 7.0 7.0 Self-emulsifying glycerin monostearate 2.5 2.5 2.5 2.5 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 0.5 0.5 Jojoba oil 5.0 5.0 5.0 5.0 5.0 5.0 B. propylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 glycerin 5.0 5.0 5.0 5.0 5.0 5.0 pericamu (montmorillonite) 5.0 5.0 5.0 5.0 5.0 5.0 acetylated hyaluronic acid ^{* 1} 0.00005 0.0001 0.001 5 10 15 Tranexamic acid 2.0 2.0 2.0 2.0 2.0 2.0 Water balance Residual residual residual residual residual ────────────────────────────────────

[0035]

[Table 11] レ プ リ カ Replica evaluation test example No. 15 16 17 18 19 20 １ 10 people 0 people 0 people 0 people 0 people 0 people 2 4 0 0 0 0 0 3 4 2 1 1 1 0 0 4 2 4 4 4 3 3 3 5 0 4 5 6 7 7 7} ──────────────── Panel total 10 people 10 people 10 people 10 people 10 people 10 people ──────────────────── ────────────────

As is clear from the results in Table 11, the cream containing less than 0.0001% by weight of acetylated hyaluronic acid (Test Example 15) does not have a remarkable effect of improving skin roughness. In addition, creams containing 0.0001 to 10% by weight of acetylated hyaluronic acid (Test Examples 16 to 19) may show an improvement in skin roughening effect by increasing the amount of acetylated hyaluronic acid. Recognize. On the other hand, the cream containing less than 10% by weight of the acetylated hyaluronic acid (Test Example 20) has an improved effect of improving skin roughness compared to the cream containing 10% by weight (Test Example 19). It turns out that is not seen. Therefore, it is understood that the amount of the acetylated hyaluronic acid is suitably 0.0001 to 10% by weight.

Amounts of Tranexamic Acid [Test Examples 21-26] Creams of various formulas with different amounts of tranexamic acid shown in Table 12 were subjected to skin roughness improvement effect tests on a human body panel, and the results are shown in Table 13. . In addition,
The cream was produced in accordance with Example 1 and Comparative Example. The test method for improving skin roughness is the same as in Example 1 and Comparative Example, except that 30 skin roughness panels are divided into three groups, and two creams of Test Examples 21 to 26 are applied to the left and right halves of the face, respectively. Was. Evaluation criteria are shown in Table 2.
It is as follows.

[0038]

[Table 12] 組 Composition (Cream) Test Example No. 21 22 23 24 25 26 A. Cetanol 0.5 0.5 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 7.0 7.0 Self-emulsifying glycerin monostearate 2.5 2.5 2.5 2.5 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 0.5 0.5 Jojoba oil 5.0 5.0 5.0 5.0 5.0 5.0 B. propylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 glycerin 5.0 5.0 5.0 5.0 5.0 5.0 pericamu (montmorillonite) 5.0 5.0 5.0 5.0 5.0 5.0 acetylated hyaluronic acid ^{* 1} 0.1 0.1 0.1 0.1 0.1 0.1 tranexamic acid 0.005 0.01 0.1 5 10 15 water balance remaining Residual residual residual residual ────────────────────────────────────

[0039]

[Table 13] レ プ リ カ Replica evaluation test example No. 21 22 23 24 25 26 ──────────────────────────────────── 1 point 2 people 0 people 0 people 0 people 0 Name 0 2 5 0 0 0 0 3 3 2 1 0 0 0 1 0 4 0 5 5 3 3 1 5 0 3 4 7 8 8} ───────────────── Panel total 10 10 10 10 10 10 ───────────────────────── ───────────

As is clear from the results shown in Table 13, the cream (Test Example 21) containing less than 0.01% by weight of tranexamic acid does not have a remarkable effect of improving rough skin. The amount of tranexamic acid was 0.0
Cream of 1 to 10% by weight (Test Examples 22 to 25)
The effect of improving skin roughness can be seen by increasing the blending amount of tranexamic acid. On the other hand, the cream containing more than 10% by weight (Test Example 26) shows an improvement in the rough skin improving effect as compared with the cream containing 10% by weight of tranexamic acid (Test Example 25). It turns out there is no. Therefore, it is understood that the blending amount of tranexamic acid is suitably from 0.01 to 10% by weight.

Combination weight ratio of acetylated hyaluronic acid to tranexamic acid [Test Examples 27 to 32] Creams of various formulas having different combination weight ratios of acetylated hyaluronic acid and tranexamic acid shown in Table 14 were used to improve skin roughness on a human body panel. The test was performed and the results are shown in Table 15. The method for producing the cream was the same as in Example 1 and Comparative Example. The test method for improving skin roughness is the same as that in Example 1 and Comparative Example, except that 30 rough skin panels were divided into three groups, and two creams of Test Examples 27 to 32 were applied to the left and right halves of the face, respectively. Was. The evaluation criteria are as shown in Table 2.

[0042]

[Table 14] ──────────────────────────────────── Composition (cream) Test example No. 27 28 29 30 31 32 A. Cetanol 0.5 0.5 0.5 0.5 0.5 0.5 Vaseline 2.0 2.0 2.0 2.0 2.0 2.0 Squalane 7.0 7.0 7.0 7.0 7.0 7.0 Self-emulsifying glycerin monostearate 2.5 2.5 2.5 2.5 2.5 2.5 POE (20) sorbitan monostearate 1.5 1.5 1.5 1.5 1.5 1.5 Pantothenyl ethyl ether 0.5 0.5 0.5 0.5 0.5 0.5 Jojoba oil 5.0 5.0 5.0 5.0 5.0 5.0 B. Propylene glycol 5.0 5.0 5.0 5.0 5.0 5.0 Glycerin 5.0 5.0 5.0 5.0 5.0 5.0 Pericamu (montmorillonite) 5.0 5.0 5.0 5.0 5.0 5.0 Aceylated hyaluronic acid 10 6 0.1 0.001 0.001 0.001 Tranexamic acid 0.1 0.1 0.1 1 5 10 Water residue residue residue Remainder Remainder Remainder ──────────────────────────────────── Compounding ratio (AcHA / TA) 100/1 60/1 1/1 1/100 1/5000 1/10000 ─────────────────────────────────── ─

[0043]

[Table 15] レ プ リ カ Replica evaluation test example No. 27 28 29 30 31 32 ──────────────────────────────────── 10 people 0 people 0 people 0 people 0 people 0 people 2 0 0 0 0 0 0 3 1 0 1 0 1 0 1 1 4 3 4 4 5 4 3 3 5 6 6 4 5 7 7} ──────────────── Panel total 10 10 10 10 10 10 ────────────────────────── ──────────

As is clear from the results in Table 15, the weight ratio of acetylated hyaluronic acid to tranexamic acid was 1 /
60/1 compared with the cream (Test Example 29)
No. 28 (Test Example 28) shows an improvement in skin roughness improvement effect. On the other hand, a cream in which the ratio of acetylated hyaluronic acid was increased beyond 60/1 (Test Example 27)
It can be seen that no improvement in the effect of improving rough skin is observed in the case of the cream of 60/1 (Test Example 28).

The cream (Test Example 31) in which the weight ratio of acetylated hyaluronic acid to tranexamic acid was 1/5000 (Test Example 31) was more effective in improving skin roughness than the cream of 1/100 (Test Example 30). Can be On the other hand, it can be seen that the cream containing more than 1/5000 (Test Example 32) cannot improve the skin roughness improvement effect as compared with the 1/5000 cream (Test Example 31). . Therefore, it is understood that the proper weight ratio of acetylated hyaluronic acid to tranexamic acid is about 60/1 to 1/5000.

Examples will be shown below to make the skin external preparation of the present invention more specific. When the same evaluation as in Example 1 was performed, the external preparation for skin in each example was the same as that in Example 1.
As well as the above, excellent skin roughness prevention and skin roughness improvement effects were exhibited.

Example 2 Cream Composition Compounding Amount (%) Stearic acid 10.0 Stearyl alcohol 4.0 Butyl stearate 8.0 Monoglycerin stearate 2.0 Vitamin E acetate 0.5 Vitamin A palmitate 0.1 Macadamia nut oil 1.0 Fragrance 0.4 Preservative Adequate amount B . Glycerin 4.0 1,2, pentanediol 3.0 Acetylated hyaluronic acid (acetylation degree 4) 1.0 Potassium hydroxide 0.4 Magnesium phosphate ascorbate 0.1 Tranexamic acid 0.05 Trisodium edetate 0. 05 Purified Water Residue -Preparation Method- The oil phase of A and the water phase of B are each heated to 70 ° C. and completely dissolved. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream.

Example 3 Cream Composition Compounding Amount (%) Cetanol 4.0 Vaseline 7.0 Isopropyl myristate 8.0 Squalane 15.0 Monoglycerin stearate 2.2 POE (20) Sorbitan monostearate 2.8 Vitamin E nicotinate 2.0 Fragrance 0.3 Antioxidant Appropriate amount Preservative Appropriate amount B. Glycerin 10.0 Acetylated hyaluronic acid (acetylation degree 2) 0.02 Dipropylene glycol 4.0 Sodium pyrrolidonecarboxylate 1.0 Tranexamic acid 3.0 Disodium edetate 0.01 Purified water Residue In Example 1 A cream was obtained according to the formula.

Example 4 Emulsion Composition Compounding Amount (%) Squalane 5.0 Oleyl oleate 3.0 Vaseline 2.0 Sorbitan sesquioleate 0.8 POE (20) oleyl ether 1.2 Evening primrose oil 0.5 Fragrance 0.3 Preservatives Appropriate amount B. 1,3 butylene glycol 4.5 Melissa extract 1.5 acetylated hyaluronic acid (acetylation degree 3.5) 0.001 ethanol 3.0 carboxyvinylporlimer 0.2 potassium hydroxide 0.1 tranexamic acid 0. 5 Sodium hexametaphosphate 0.05 Purified water Residue Emulsion was obtained according to Example 1.

Example 5 Foundation Composition Compounding Amount (%) Cetanol 3.5 Deodorized lanolin 4.0 Jojoba oil 5.0 Vaseline 2.0 Squalane 6.0 Monoglycerin stearate 2.5 POE (60) hydrogenated castor oil 1.5 POE (20) cetyl ether 1.0 Pyridoxine Tripalmitate 0.1 Preservative qs perfume 0.3 B. Propylene glycol 10.0 Acetylated hyaluronic acid (acetylation degree 2.9) 0.05 Compounded powder 12.0 Tranexamic acid 5.0 Trisodium edetate 0.2 Purified water Residue Got a foundation.

Example 6 Toner Composition Composition Amount (%) Ethanol 5.0 POE oleyl alcohol ether 2.0 2-ethylhexyl-P-dimethylaminobenzoate 0.18 preservatives qs perfume 0.05 B. 1,3 butylene glycol 9.5 sodium pyrrolidonecarboxylate 0.5 acetylated hyaluronic acid (degree of acetylation 3.5) 5.0 nicotinamide 0.3 glycerin 5.0 hydroxypropyl β-cyclodextrin 1.0 citric acid 0.05 Sodium citrate 0.1 Tranexamic acid 1.0 Purified water Residue -Preparation method- The alcohol phase of A was added to the aqueous phase of B and solubilized to obtain a lotion.

Example 7 Pack Composition Composition (%) (1) Polyvinyl alcohol 10.0 (2) Polyethylene glycol (molecular weight 400) 0.4 (3) Glycerin 3.0 (4) Ethanol (95%) 8.0) (5) Acetylated hyaluronic acid (acetylation degree 3) 0.1 (6) Tranexamic acid 0.1 (7) Preservative 0.1 (8) Fragrance 0.1 (9) Purified water residue- Production method-(4), (7) and (8) are mixed and dissolved at room temperature, and (1)
(2) (3) and (5) (6) (9) were mixed and dissolved at 80 ° C., and the mixture was stirred and added, and then allowed to cool to room temperature to obtain a pack.

[Example 8] Lipstick composition Compounding amount (%) Castor oil 20.0 Cetyl alcohol 20.0 Beeswax 5.0 Candelilla wax 30.0 Acetylated hyaluronic acid (acetylation degree 4) 0.0001 Squalane 13.0 Carnauba wax 5.0 Pigment 5.0 Tranexamic acid 0.01 Perfume Appropriate amount-Production method-Mixed and dissolved at 80 ° C, poured into a mold, allowed to cool to room temperature, and removed from the mold to obtain a stick-like lipstick. .

[0054]

The external preparation for skin of the present invention has the advantage that the effect of preventing skin roughness and improving skin roughness can be significantly increased by blending tranexamic acid with acetylated hyaluronic acid.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 7/48 A61K 7/48

Claims (1)

[Claims] 1. An acetylated hyaluronic acid having 0.004 to 10% by weight, wherein the number of substitutions of an acetyl group is 2 to 4 per hyaluronic acid structural unit, and 0.01 of tranexamic acid.
Acetylated hyaluronic acid and tranexamic acid in a weight ratio of 60/1 to 1/500.
An external preparation for skin, characterized by being 0.