KR101232647B1 - Kojic acid derivative having antiaging activity, preparation method thereof and cosmetic composition containing the same - Google Patents

Abstract

(상기 화학식에서
R₁ 은 S, SO 또는 SO₂이고, R₂ 는 수소, 히드록시기 또는 메톡시기이다)
상기 코지산 유도체 화합물은 피부내에서 항산화활성 및 콜라겐 생성촉진효과를 나타내므로 피부노화방지용 화장료 조성물로 유용하게 사용될 수 있다.The present invention relates to a kojic acid derivative represented by the following Chemical Formula 1 having an anti-aging activity, a preparation method thereof, and an anti-aging cosmetic composition containing the same.
[Formula 1]

(In the above formula
R ₁ is S, SO or SO ₂ , and R ₂ is hydrogen, a hydroxy group or a methoxy group)
Since the kojic acid derivative compound exhibits antioxidant activity and collagen production promoting effect in the skin, it may be usefully used as a cosmetic composition for preventing skin aging.

Description

Kojic acid derivative having anti-aging activity, preparation method thereof, and anti-aging cosmetic composition comprising the same

The present invention relates to a kojic acid derivative compound of Formula 1 having an anti-aging activity, a preparation method thereof and an anti-aging cosmetic composition comprising the same.

[Formula 1]

In the above formula

R ₁ is S, SO or SO ₂ , and R ₂ is hydrogen, a hydroxy group or a methoxy group.

Skin is the body's primary protective film that protects organs in the body from changes in temperature and humidity, stimuli from the external environment such as ultraviolet rays and pollutants, and plays an important role in maintaining homeostasis such as body temperature control. However, excessive physical and chemical stimuli and stress malnutrition from the outside degrade the skin's normal function and promote skin aging such as loss of elasticity, keratinization and wrinkle formation, which prevents this phenomenon and makes the skin healthier and more elastic. In order to maintain the conventional use of cosmetics reinforced with bioactive substances obtained from various plants, microorganisms, etc., efforts have been made to effectively maintain skin's inherent functions and to effectively inhibit skin aging by activating skin cells. However, existing cosmetic raw materials have various problems such as insufficient efficacy or skin side effects. Therefore, research on raw materials having an anti-aging effect without causing skin side effects has been actively conducted. As a result of this study, the present invention has found an excellent anti-aging effect by using novel kojic acid derivatives as a skin external preparation composition.

Kojic acid is a substance obtained by culturing strains such as Aspergillus, and has an effect of strongly inhibiting the activity of tyrosinase enzymes involved in forming melanin, which is an important factor for determining the tone of human skin. The active mechanism of kojic acid is known to be formed by inhibiting the melanin forming action of tyrosinase by forming chelates with copper ions contained in tyrosinase in 5-position hydroxyl group and 4-position carbonyl group. For this reason, many kojic acid derivatives have been synthesized and studied for the purpose of enhancing tyrosinase activity. However, little research has been conducted on the efficacy of other than tyrosinase inhibitory effects. The present inventors synthesized various kojic acid derivatives and tested the effects, and found that the kojic acid derivative compounds according to the present invention can be used in an anti-aging cosmetic composition having excellent antioxidant and cholesterol biosynthesis effects, thereby completing the present invention. It was.

The present invention is to solve the problems of the prior art as described above, it is an object to provide a kojic acid derivative compound having an anti-aging activity.

Another object of the present invention is to provide a method for preparing the kojic acid derivative compound.

Furthermore, another object of the present invention is to provide a cosmetic composition for preventing skin aging, which is excellent in antioxidant activity and collagen production promoting effect in skin cells by containing the kojic acid derivative compound as an active ingredient.

According to the present invention to achieve the above object, there is provided a kojic acid derivative compound represented by the following formula (1) having anti-aging activity.

[Formula 1]

In the above formula

R ₁ is S, SO or SO ₂ , and R ₂ is hydrogen, a hydroxy group or a methoxy group.

Kojic acid derivative compounds wherein R ₁ is SO or SO ₂ in the above formula are more stable forms of the compound and thus more stable in the formulation.

The compound is prepared by reacting chlorinated kojic acid with benzenethiol, hydroxy benzenethiol or methoxy benzenethiol in the presence of a base and oxidizing with an oxidizing agent under certain conditions.

According to the present invention to achieve another object, there is provided a cosmetic composition for preventing skin aging comprising 0.1 to 10% by weight of the kojic acid derivative compound of Formula 1 relative to the total weight of the cosmetic composition.

Kojic acid derivatives prepared according to the present invention can be usefully used as an anti-aging cosmetic composition and skin wrinkle improvement because it has an excellent antioxidant effect and collagen production promoting effect in skin cells.

Hereinafter, the present invention will be described in detail.

According to the present invention there is provided a kojic acid derivative compound of Formula 1 having anti-aging activity.

[Formula 1]

In the above formula

R ₁ is S, SO or SO ₂ , and R ₂ is hydrogen, a hydroxy group or a methoxy group.

The kojic acid derivative compound may be prepared as in the following scheme.

[Reaction Scheme 1]

[Reaction Scheme 2]

Scheme 3

R ₂ in the above scheme is hydrogen, hydroxy group or methoxy group.

Hereinafter, the reaction schemes will be described in detail.

Scheme 1 shows the preparation of the sulfur compound of Formula II from chloric acid. The sulfur compound of Formula II is prepared by reacting any one selected from the group consisting of chlorinated kojic acid with benzenethiol, hydroxy benzenethiol and methoxy benzenethiol in the presence of an organic base. Pyridine, triethylamine, etc. may be used as the organic base, and dichloromethane, chloroform, tetrahydrofuran, etc. may be used as the organic solvent. Reaction temperature is 10-80 degreeC, Preferably it is made to react at about 40 degreeC.

Scheme 2 shows that the sulfoxide compound of Formula III is prepared by oxidizing the sulfur compound prepared in Scheme 1.

The sulfur group of the compound of formula II prepared in the above step is oxidized using metachloroperbenzoic acid (MCPBA), which is an oxidizing agent, to convert to a sulfoxide compound. In this case, as the oxidizing agent, metachloroperbenzoic acid (MCPBA) should be used exactly equivalent to the compound of formula II. Dichloromethane, chloroform, tetrahydrofuran, etc. can be used as an organic solvent. As for reaction temperature, about 25-28 degreeC is preferable. If the temperature is higher than this, a sulfone compound may be formed, and if it is lower than this, an unreactant may be produced.

Scheme 3 shows that the sulfone compound of Formula IV is prepared by oxidizing the sulfur compound prepared in Scheme 1.

The sulfur group of the compound of formula (II) prepared in the above step is oxidized using Oxone (Oxone) to convert into a sulfone compound. As the oxidizing agent, metaxone (Oxone) should be used in an amount of 2.0 to 2.5 times, preferably 2.2 times, based on the compound of formula II. As a solvent, terrahydrofuran, acetone, dioxane, or the like, which is an organic solvent, is mixed with water and used. The mixing ratio of water and organic solvent is most preferably 1: 1. Moreover, as for reaction temperature, 25-50 degreeC is preferable. If the temperature is lower than this, sulfoxide compounds may be formed together.

Kojic acid compound represented by the formula (1) prepared according to the present invention can be usefully applied to the anti-aging cosmetic composition because it shows an excellent effect on skin wrinkles and antioxidants. The sulfoxide and sulfone compounds prepared in Schemes 2 and 3 are more stable compounds than the compounds of Scheme 1, and thus more stable in formulations such as cosmetics.

Kojic acid derivative compounds according to the invention can be used in the skin cosmetic composition, there is no particular limitation in the formulation. For example, supple cosmetics, astringent cosmetics, nourishing cosmetics, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil, body It may be formulated into cosmetic compositions such as essences, makeup bases, foundations, hair dyes, shampoos, rinses, body cleansers, ointments, patches or sprays. Each of these formulations may contain various bases and additives necessary and appropriate for the formulation of the formulation.

Hereinafter, preferred examples are provided to help understanding of the present invention, but the following examples are merely to illustrate the present invention, and the scope of the present invention is not limited to the following examples.

[Example]

Example 1: Synthesis of 5-hydroxy-2-((phenylthio) methyl) -4H-pyran-4-one

In 200 mL of tetrahydrofuran, chloro kojic acid (10.0 g), benzenethiol (7.5 g) and triethylamine (7.5 g) were added, and the reaction temperature was raised to 40 ° C and stirred for 5 hours. After completion of the reaction, TLC confirmed and concentrated to give a solid compound. This was again dissolved in 500 mL of ethyl acetate, washed twice with 5% aqueous HCl solution (100 mL), dried over magnesium sulfate, concentrated to half, and the precipitated crystals were filtered to give 11.5 g (79% yield) of the pure target compound.

¹ H NMR (300 MHz, DMSO-d ₆ ): 9.07 (s, 1H), 7.97 (s, 1H), 7.26-7.35 (m, 5H), 6.21 (s, 1H), 4.10 (s, 2H).

Example 2: Synthesis of 2-((4-hydroxyphenylthio) methyl) -5-hydroxy-4H-pyran-4-one

A target compound (10.1 g, 70%) was obtained in the same manner as in Example 1, except that 4-hydroxy benzenethiol was used instead of benzenethiol.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.76 (s, 1H), 9.02 (s, 1H), 7.95 (s, 1H), 7.17 (d, 2H, J = 8.4 Hz), 6.68 (d, 2H , J = 8.4 Hz), 5.98 (s, 1 H), 3.84 (s, 2 H).

Example 3: Synthesis of 2-((3-hydroxyphenylthio) methyl) -5-hydroxy-4H-pyran-4-one

The target compound (10.0 g, 65%) was obtained using the same method as Example 1 except for using 3-hydroxy benzenethiol instead of benzenethiol.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.62 (s, 1H), 9.08 (s, 1H), 8.03 (s, 1H), 7.11 (m, 1H), 6.76 (m, 2H), 6.61 (d , 1H, J = 8.1 Hz), 6.28 (s, 1H), 4.10 (s, 2H).

Example 4: Synthesis of 2-((2-hydroxyphenylthio) methyl) -5-hydroxy-4H-pyran-4-one

A target compound (11.2 g, 72%) was obtained using the same method as Example 1 except for using 2-hydroxy benzenethiol instead of benzenethiol.

¹ H NMR (300MHz, DMSO-d ₆ ): 10.02 (s, 1H), 9.10 (s, 1H), 7.97 (s, 1H), 7.21 (d, 1H, J = 7.5 Hz), 7.10 (m, 1H ), 6.83 (d, 1H, J = 8.1 Hz), 6.74 (m, 1H), 6.14 (s, 1H), 4.00 (s, 2H).

Example 5: Synthesis of 2-((4-methoxyphenylthio) methyl) -5-hydroxy-4H-pyran-4-one

A target compound (13.2 g, 80%) was obtained using the same method as Example 1 except for using 4-methoxy benzenethiol instead of benzenethiol.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.02 (s, 1H), 7.96 (s, 1H), 7.29 (d, 2H, J = 8.4 Hz), 6.87 (d, 2H, J = 8.4 Hz), 6.04 (s, 1 H), 3.92 (s, 2 H), 3.69 (s, 3 H).

Example 6: Synthesis of 2-((3-methoxyphenylthio) methyl) -5-hydroxy-4H-pyran-4-one

The target compound (13.4 g, 82%) was obtained using the same method as Example 1 except for using 3-methoxy benzenethiol instead of benzenethiol.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.12 (s, 1H), 8.03 (s, 1H), 7.23 (m, 1H), 6.92 (m, 2H), 6.79 (d, 1H, J = 7.5 Hz ), 6.29 (s, 1 H), 4.18 (s, 2 H), 3.73 (S, 3 H).

Example 7: Synthesis of 2-((2-methoxyphenylthio) methyl) -5-hydroxy-4H-pyran-4-one

A target compound (12.3 g, 75%) was obtained using the same method as Example 1 except for using 2-methoxy benzenethiol instead of benzenethiol.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.02 (s, 1H), 8.00 (s, 1H), 7.27 (m, 2H), 7.02 (d, 1H, J = 7.5 Hz), 6.90 (m, 1H ), 6.20 (s, 1 H), 4.04 (s, 2 H), 3.80 (s, 3 H).

Example 8: Synthesis of 5-hydroxy-2-((phenylsulfinyl) methyl) -4H-pyran-4-one

5-hydroxy-2-((phenylthio) methyl) -4H-pyran-4-one (10 g) obtained in Example 1 was dissolved in 200 mL of methylene chloride, and then 7.3 g of metachloroperbenzoic acid (MCPBA) was added thereto. Stir at room temperature for 5 hours. After completion of the reaction, TLC confirmed and concentrated to give a solid compound. This was again dissolved in 200 mL of ethyl acetate, washed twice with 5% aqueous HCl solution (100 mL), dried over magnesium sulfate, concentrated to half, and the precipitated crystals were filtered to obtain 9.4 g (88% yield) of the pure target product.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.20 (s, 1H), 7.86 (s, 1H), 7.60-7.48 (m, 5H), 6.13 (s, 1H), 4.32 (d, 1H, J = 13.5 Hz), 4.15 (d, 1H, J = 13.5 Hz).

Example 9: Synthesis of 5-hydroxy-2-((4-hydroxyphenylsulfinyl) methyl) -4H-pyran-4-one

Using the same method as in Example 8, except that 5-hydroxy-2-((4-hydroxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 2 was used The target compound (9.1 g, 80%) was obtained.

¹ H NMR (300 MHz, DMSO-d ₆ ): 10.21 (s, 1H), 9.18 (s, 1H), 7.91 (s, 1H), 7.43 (d, 2H, J = 8.4 Hz), 6.90 (d, 2H , J = 8.4 Hz), 6.13 (s, 1H), 4.18 (d, 1H, J = 13.5 Hz), 4.10 (d, 1H, J = 13.5 Hz).

Example 10 Synthesis of 5-hydroxy-2-((3-hydroxyphenylsulfinyl) methyl) -4H-pyran-4-one

Using the same method as in Example 8, except that 5-hydroxy-2-((3-hydroxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 3 was used The desired compound (8.8 g, 78%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 10.00 (s, 1H), 9.17 (s, 1H), 7.90 (s, 1H), 7.39 (m, 1H), 6.97 (m, 2H), 6.85 (d , 1H, J = 8.1 Hz), 6.16 (s, 1H), 4.24 (d, 1H, J = 13.5 Hz), 4.09 (d, 1H, J = 13.5 Hz).

Example 11: Synthesis of 5-hydroxy-2-((2-hydroxyphenylsulfinyl) methyl) -4H-pyran-4-one

Using the same method as in Example 8, except that 5-hydroxy-2-((2-hydroxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 4 was used The desired compound (9.4 g, 83%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 10.82 (s, 1H), 9.06 (s, 1H), 7.83 (s, 1H), 7.34 (m, 2H), 6.97 (m, 2H), 6.09 (s , 1H), 4.30 (d, 1H, J = 13.5 Hz), 4.03 (d, 1H, 13.5 Hz).

Example 12 Synthesis of 5-hydroxy-2-((4-methoxyphenylsulfinyl) methyl) -4H-pyran-4-one

Using the same method as in Example 8, except that 5-hydroxy-2-((4-methoxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 5 was used The target compound (9.5 g, 80%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.20 (s, 1H), 7.90 (s, 1H), 7.53 (d, 2H, 8.4 Hz), 7.10 (d, 2H, J = 8.4 Hz), 6.15 ( s, 1H), 4.25 (d, 1H, J = 13.5 Hz), 4.13 (d, 1H, J = 13.5 Hz), 3.81 (s, 3H).

Example 13: Synthesis of 5-hydroxy-2-((3-methoxyphenylsulfinyl) methyl) -4H-pyran-4-one

Using the same method as in Example 8, except that 5-hydroxy-2-((3-methoxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 6 was used The target compound (9.5 g, 80%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.20 (s, 1H), 7.89 (s, 1H), 7.43 (m, 1H), 7.14 (m, 3H), 6.15 (s, 1H), 4.26 (d , 1H, J = 13.5 Hz), 4.09 (d, 1H, J = 13.5 Hz), 3.77 (s, 3H).

Example 14 Synthesis of 5-hydroxy-2-((2-methoxyphenylsulfinyl) methyl) -4H-pyran-4-one

Using the same method as in Example 8, except that 5-hydroxy-2-((2-methoxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 7 was used The desired compound (8.3 g, 70%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.12 (s, 1H), 7.82 (s, 1H), 7.59 (m, 1H), 7.41 (d, 1H, J = 7.5 Hz), 7.20 (m, 2H ), 6.07 (s, 1H), 4.25 (d, 1H, J = 13.5 Hz), 4.04 (d, 1H, J = 13.5 Hz), 3.86 (s, 3H).

Example 15 Synthesis of 5-hydroxy-2-((phenylsulfonyl) methyl) -4H-pyran-4-one

5-hydroxy-2-((phenylthio) methyl) -4H-pyran-4-one (10 g) obtained in Example 1 was dissolved in 200 mL of a 1: 1 mixture of tetrahydrofuran and water, followed by Oxone. 39 g was added and stirred at room temperature for 5 hours. After completion of the reaction, TLC confirmed and concentrated to give a solid compound. This was again dissolved in 200 mL of ethyl acetate, washed twice with 5% aqueous HCl solution (100 mL), dried over magnesium sulfate, concentrated to half, and the precipitated crystals were filtered to obtain 7.9 g (yield 70%) of the pure target compound.

¹ H NMR (300 MHz, DMSO-d ₆ ): δ 9.32 (s, 1H), 7.96 (s, 1H), 7.65-7.84 (m, 5H), 6.22 (s, 1H), 4.83 (s, 2H).

Example 16: Synthesis of 5-hydroxy-2-((4-hydroxyphenylsulfonyl) methyl) -4H-pyran-4-one

Using the same method as in Example 15, except that 5-hydroxy-2-((4-hydroxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 2 was used The target compound (9.6 g, 80%) was obtained.

¹ H NMR (300 MHz, DMSO-d ₆ ): δ 10.75 (s, 1H), 9.29 (s, 1H), 7.98 (s, 1H), 7.62 (d, 2H, J = 8.4 Hz), 6.95 (d, 2H, J = 8.4 Hz), 619 (s, 1H), 4.68 (s, 2H).

Example 17 Synthesis of 5-hydroxy-2-((3-hydroxyphenylsulfonyl) methyl) -4H-pyran-4-one

Using the same method as in Example 15, except that 5-hydroxy-2-((3-hydroxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 3 was used The target compound (9.6 g, 80%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): δ 10.30 (s, 1H), 9.32 (s, 1H), 7.98 (s, 1H), 7.45 (m, 1H), 7.22 (d, 1H, J = 7.5 Hz), 7.11 (m, 2 H), 6.23 (s, 1 H), 4.77 (s, 2 H).

Example 18 Synthesis of 5-hydroxy-2-((2-hydroxyphenylsulfonyl) methyl) -4H-pyran-4-one

Using the same method as in Example 15, except that 5-hydroxy-2-((2-hydroxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 4 was used The desired compound (8.4 g, 70%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): δ 11.39 (s, 1H), 9.28 (s, 1H), 7.94 (s, 1H), 7.58 (m, 2H), 7.09 (d, 1H, J = 7.5 Hz), 6.96 (m, 1 H), 6.26 (s, 1 H), 4.78 (s, 2 H).

Example 19 Synthesis of 5-hydroxy-2-((4-methoxyphenylsulfonyl) methyl) -4H-pyran-4-one

Using the same method as in Example 15, except for using 5-hydroxy-2-((4-methoxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 5. The desired compound (10.1 g, 80%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.31 (s, 1H), 7.98 (s, 1H), 7. 74 (d, 2H, J = 8.4 Hz), 7.72 (d, 2H, J = 8.4 Hz ), 6.22 (s, 1 H), 4.75 (s, 2 H), 3.86 (s, 3 H).

Example 20 Synthesis of 5-hydroxy-2-((3-methoxyphenylsulfonyl) methyl) -4H-pyran-4-one

Using the same method as in Example 15, except that 5-hydroxy-2-((3-methoxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 6 was used The desired compound (8.8 g, 70%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.28 (s, 1H), 7.99 (s, 1H), 7.60 (m, 1H), 7.20-7.39 (m, 3H), 6.23 (s, 1H), 4.84 (s, 2 H), 3.83 (s, 3 H).

Example 21 Synthesis of 5-hydroxy-2-((2-methoxyphenylsulfonyl) methyl) -4H-pyran-4-one

Using the same method as in Example 15, except that 5-hydroxy-2-((2-methoxyphenylthio) methyl) -4H-pyran-4-one (20 g) obtained in Example 6 was used The target compound (10.1 g, 80%) was obtained.

¹ H NMR (300MHz, DMSO-d ₆ ): 9.25 (s, 1H), 7.94 (s, 1H), 7.71 (m, 2H), 7.34 (d, 1H, J = 7.5 Hz), 7.16 (m, 1H ), 6.27 (s, 1 H), 4.79 (s, 2 H), 3.97 (s, 3 H).

Test Example 1 Measurement of Antioxidant Effect Using a HaCat Model

The antioxidant effects of Kojic acid derivatives prepared in Examples 1 to 21 were measured. A human keratinocyte HaCaT cell line was dispensed at 1.0 × 10 ⁶ per 60 mm dish and incubated for one day at 37 ° C. and 5% CO ₂ conditions using DMEM (FBS 10%) medium containing penicillin / streptomycin. 10 ^-4 molarity and tocopherol and resveratrol were also treated at the same concentration for 24 hours. After treatment with 4 mM BHT (t-butyl hydroperoxide) at the same time with the composition, cells were obtained after incubation for 4 hours at 37 ° C. and 5% CO ₂ . The cells were lysed (freeze / thawing) by repeating the freezing / thawing process, and the following test was performed according to the method described in the assay kit.

In the present invention, Calbiochem Lipid peroxidation assay kit (Calbiochem Lipid peroxidation assay kit; Cat. No. 437634) was used as a reagent, malondialdehyde (malondialdehyde, MDA) and 4-hydroxyalkenals (hydoxyalkenals; 4-hydroxy). Lipid peroxidation was measured using the principle that peroxides of esters associated with long chain unsaturated fatty acids such as -2 (E) -nonenal, 4-HNE) react with the reagents to form stable compounds at 586 nm.

The results are shown in Table 1 below.

matter MDA, HNE matter MAD, HNE Untreated group 100 Example 10 167 t-BHT 320 Example 11 165 Kojic acid 280 Example 12 180 Example 1 200 Example 13 160 Example 2 160 Example 14 165 Example 3 165 Example 15 170 Example 4 162 Example 16 165 Example 5 175 Example 17 158 Example 6 180 Example 18 155 Example 7 181 Example 19 190 Example 8 190 Example 20 188 Example 9 161 Example 21 170

From the antioxidant test results of Table 1, it was confirmed that the kojic acid derivatives prepared in Examples 1 to 21 showed higher antioxidant efficacy than kojic acid. In particular, compounds having a hydroxy group in the benzene ring, as shown in Examples 2, 3, 4, 9, 10, 11, 16, 17, 18 showed a high antioxidant effect.

Test Example 2: Collagen Biosynthesis Promoting Effect

The collagen biosynthesis promoting effect of kojic acid derivatives obtained from Examples 1 to 21 was measured and compared with kojic acid. To investigate collagen biosynthesis promoting effect, human normal fibroblasts were inoculated to 1 × 10 ⁴ cells in each well of a 96-well microplate, and then DMEM (dulbecco's Modified Eagle's). Medium) incubate for 24 hours in medium. After culturing, the kojic acid derivatives of the examples prepared above were replaced with serum-free DM medium adjusted to a final concentration of 500 μg / ml, followed by further incubation for 48 hours. 50 μg / ml of ascorbic acid is added to promote collagen synthesis 24 hours before the last 24 hours of culture. After incubation, each well is washed, replaced with DM medium without serum, and incubated for another 24 hours. After incubation, the supernatant of each well was collected, and the amount of newly synthesized collagen was measured by the amount of PICP using a kit (Kit, Takara, Kyoto, Japan) using procollagen type I-peptide (PICP). PICP amount is shown in Table 2 below to synthesize the collagen in terms of ng / 2X10 ⁴ cells.

Substance (500 µg / ml) Collagen Synthesis
(ng / 2X10 ⁴ ) Substance (500 µg / ml) Collagen Synthesis
(ng / 2X10 ⁴ ) Control group 100 Example 11 118 Kojic acid 105 Example 12 120 Example 1 135 Example 13 117 Example 2 137 Example 14 120 Example 3 136 Example 15 119 Example 4 130 Example 16 124 Example 5 128 Example 17 130 Example 6 127 Example 18 135 Example 7 130 Example 19 127 Example 8 134 Example 20 126 Example 9 122 Example 21 130 Example 10 129

From the collagen biosynthesis promotion results of Table 2, kojic acid compounds prepared in Examples 1 to 21 were identified as compounds having an excellent collagen biosynthesis promoting effect. However, Kojisan showed a slight effect.

Formulation Example 1: Preparation of Nutrients (Milk Lotion)

Nutritional longevity containing the kojic acid derivative compound prepared in Example 1 was prepared according to the composition of Table 3.

ingredient Content (% by weight) glycerin 8.0 Butylene glycol 4.0 Hyaluronic acid extract 5.0 Beta Glucan 7.0 Carbomer 0.1 Kojic acid derivative compound (Example 1) 2.0 Caprylic Capric Triglycerides 8.0 Squalane 5.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Cetearyl Alcohol 1.0 antiseptic Suitable amount incense Suitable amount Pigment Suitable amount Triethanolamine 0.1 Purified water Balance

Formulation Example 2: Preparation of Nutritional Cream

Nutritional cream containing kojic acid derivative compound prepared in Example 1 was prepared according to the composition of Table 4.

ingredient Content (% by weight) glycerin 3.0 Butylene glycol 3.0 Liquid paraffin 7.0 Beta Glucan 7.0 Carbomer 0.1 Kojic acid derivative compound (Example 1) 1.0 Caprylic Capric Triglycerides 3.0 Squalane 5.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Polysorbate 60 1.2 antiseptic Suitable amount incense Suitable amount Pigment Suitable amount Triethanolamine 0.1 Purified water Balance

Formulation Example 3: Preparation of Massage Cream

A nourishing cream containing kojic acid derivative compound prepared in Example 9 was prepared according to the composition of Table 5 below.

ingredient Content (% by weight) glycerin 8.0 Butylene glycol 4.0 Liquid paraffin 45.0 Beta Glucan 7.0 Carbomer 0.1 Kojic acid derivative compound (Example 9) 2.0 Caprylic Capric Triglycerides 3.0 Wax 4.0 Cetearyl Glucoside 1.5 Sesqui oleic acid sorbitan 0.9 Vaseline 3.0 antiseptic Suitable amount incense Suitable amount Pigment Suitable amount paraffin 1.5 Purified water Balance

Formulation Example  4: Manufacture of ointments

An ointment containing the kojic acid derivative compound prepared in Example 9 was prepared according to the composition of Table 6 below.

ingredient Content (% by weight) glycerin 8.0 Butylene glycol 4.0 Liquid paraffin 15.0 Beta Glucan 7.0 Carbomer 0.1 Kojic acid derivative compound (Example 9) 1.0 Caprylic Capric Triglycerides 3.0 Squalane 1.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Cetearyl Alcohol 1.0 antiseptic Suitable amount incense Suitable amount Pigment Suitable amount Wax 4.0 Purified water Balance

Claims (7)

delete delete delete delete An anti-aging cosmetic composition comprising the following formula 1 compound 0.1 to 10% by weight based on the total weight of the cosmetic composition.
[Formula 1]

(In the above formula
R ₁ is S, SO or SO ₂ , and R ₂ is hydrogen, a hydroxy group or a methoxy group) The anti-aging cosmetic composition according to claim 5, wherein the cosmetic composition has antioxidant activity. The anti-aging cosmetic composition according to claim 5, wherein the cosmetic composition has collagen biosynthesis promoting activity.