KR100740575B1 - 2,3-dihydroxybenzoic acid derivatives, the preparation method thereof, and the whitening cosmetic composition containing the same - Google Patents

Abstract

2,3-Dihydroxybenzoic acid derivatives, a preparation method thereof, and a skin-whitening cosmetic composition containing the same compounds are provided to inhibit activity of tyrosinase and melanin formation while cytotoxicity of the compounds is very low, so that the compounds are useful for improvement of pigmentation in the skin. The method for preparing the 2,3-dihydroxybenzoic acid derivatives represented by the formula(1) comprises the steps of: (A) reacting 2,3-dihydroxybenzoic acid with acetic acid anhydride in the presence of base to prepare a 2,3-diacetyloxybenzoic acid compound represented by the formula(2); (B) preparing an amide compound represented by the formula(3) from the 2,3-diacetyloxybenzoic acid compound by using ethylchloroformate and amine having a lipophilic group; and (C) hydrolyzing an acetyl group of the amide compound represented by formula (3) to prepare 2,3-dihydroxybenzoic acid represented by the formula (1), wherein R is 4-ethoxyphenyl, 2-cyclohexenylethyl, cycloheptyl, cyclohexyl, tert-octyl, 4-isopropylphenyl, 2,3-dihydrobenzo[1,4]dioxin-7-yl, benzo[1,3]-dioxol-6-yl or adamantyl-1-yl; and the amine having the lipophilic group is an amine selected from 4-ethoxyphenylamine, 2-cyclohexenylethylamine, cycloheptylamine, cyclohexylamine, tert-octylamine, 4-isopropylphenylamine, 2,3-dihydrobenzo[1,4]dioxin-7-amine, benzo[1,3]-dioxol-6-amine or adamantyl-1-amine. The skin-whitening cosmetic composition contains 0.01-20 wt.% of the 2,3-dihydroxybenzoic acid derivatives represented by the formula(1).

Description

2,3-dihydroxybenzoic acid derivative compound, a method for preparing the same and a whitening cosmetic composition containing the same {2,3-dihydroxybenzoic acid derivatives, the preparation method approximately, and the whitening cosmetic composition containing the same}

The present invention relates to a 2,3-dihydroxybenzoic acid derivative compound represented by the following formula (1), a preparation method thereof, and a whitening cosmetic composition using the same as an active ingredient. More specifically, reacting 2,3-dihydroxybenzoic acid and acetic anhydride in the presence of a base to prepare a 2,3-diacetyloxybenzoic acid compound; Preparing an amide compound from the resulting 2,3-diacetyloxybenzoic acid compound using ethylchloroformmate and a lipophilic group; The present invention relates to a 2,3-dihydroxy benzoic acid derivative compound, which is prepared by a method comprising hydrolyzing an acetyl group of an amide compound to prepare a 2,3-dihydroxybenzoic acid derivative compound. The 2,3-dihydroxybenzoic acid derivative of the compound is low in cytotoxicity and excellent in inhibiting tyrosinase inhibition and melanin production, and the cosmetic composition containing the same has the effect of improving the pigmentation of the skin for the purpose of whitening. It can be used as a cosmetic.

[Formula 1]

In the above formula,

Human skin color varies according to race, region, gender, age, and individual, and may also be different for each part of the same person and also seasonally. Human skin color is affected by the presence or absence of pigments such as melanin, hemoglobin or carotenoids produced by the melanocytes, the pigment cells present in the epidermis, and the thickness and reflectivity of the skin, among which melanin plays an important role. Melanin in the epidermal layer, which is the outer skin of the skin, acts as a sunscreen to protect the skin organs under the dermis and to capture free radicals generated in the skin's living body, thereby protecting proteins and genes in the skin. However, melanin produced by internal and external stress stimulus is a stable substance that does not disappear until it is released to the outside through skin keratinization even if the stress disappears. In addition, the production of free radicals in the skin is increased or inflammation due to the polymerization oxidation process using an enzyme such as Tyrosinase as a substrate using Tyrosine or DOPA in vivo. Melanin production increases when there is a reaction or when exposed to ultraviolet light. In particular, ultraviolet rays may increase the production of melanin, which may partially cause melanin to develop into blemishes, resulting in undesired results, or even worse, may cause skin cancer and the like, and may pose a risk to life. Due to the above reasons, many melanin inhibitors such as ointments, creams, and lotions containing kojic acid, arbutin, glutathione, vitamin A, vitamin C, etc. have been developed, but there are no whitening products having a whitening effect that is satisfactory to consumers. to be. In addition, the hydroquinone-containing whitening agent has an excellent whitening effect, but its cytotoxicity is severe and its use is limited. In addition, compounds such as hydroquinone fatty acid ester compounds such as hydroquinone monocaprylate, hydroquinone monolaurylate, and hydroquinone monopalmitate are prepared as derivatives and used as cosmetic raw materials. Even if it is reduced, the whitening effect is also insignificant or stability in many cases.

Accordingly, the present inventors have studied polyphenol-based compounds for the purpose of solving the problems of the conventional whitening agent, and synthesized various lipophilic groups into amide compounds using 2,3-dihydroxybenzoic acid as a matrix, and 2,3-di The 2,3-dihydroxybenzoic acid derivative compound in which hydroxybenzoic acid is bound to a specific amide structure has been found to be excellent in inhibiting melanogenesis and low in cytotoxicity, thus completing the present invention.

The reason why the 2,3-dihydroxybenzoic acid derivatives show high whitening effect and low cytotoxicity is that two neighboring hydroxy groups are adjacent to the carbonyl group to change the electron arrangement of the molecule and the lipophilic amide group. Due to interaction.

Accordingly, an object of the present invention is to provide a 2,3-dihydroxybenzoic acid derivative compound represented by the following general formula (1) and a method for producing the same.

[Formula 1]

In the above formula,

Furthermore, another object of the present invention is to provide a whitening cosmetic composition containing the aforementioned 2,3-dihydroxybenzoic acid derivative compound in an amount of 0.01 to 20% by weight.

In order to achieve the above object, the 2,3-dihydroxybenzoic acid derivative compound of the present invention,

(A) reacting 2,3-dihydroxybenzoic acid and acetic anhydride in the presence of a base to prepare a 2,3-diacetyloxybenzoic acid compound;

(B) preparing an amide compound from the 2,3-diacetyloxybenzoic acid compound produced in step (A) using ethylchloroformmate and a lipophilic group; And

(C) hydrolyzing the acetyl group of the amide compound produced in step (B) to prepare a 2,3-dihydroxybenzoic acid derivative compound;

Characterized in that prepared by the above method comprising a.

In addition, the whitening cosmetic composition of the present invention is characterized in that it contains 0.01 to 20.0% by weight of the 2,3-dihydroxybenzoic acid derivative compound.

Hereinafter, the present invention will be described in more detail.

The method for preparing 2,3-dihydroxybenzoic acid derivative compound according to the present invention may be represented by the following Scheme 1.

In the above formula,

Method for producing a 2,3-dihydroxybenzoic acid derivative compound according to the present invention, as can be seen in the above scheme I, specifically described as follows.

(A) reacting 2,3-dihydroxybenzoic acid and acetic anhydride in the presence of a base to prepare a 2,3-diacetyloxybenzoic acid compound represented by (2) in Scheme 1 above:

In step (A) of the preparation method of the present invention, pyridine, triethylamine, dimethylaminopyridine, and the like may be used. It is preferable to use dimethylaminopyridine or dimethylaminopyridine together with other bases. If dimethylaminopyridine is not used, it is difficult to proceed with the reaction and the yield is low, so there is a disadvantage in that an excessive amount of base is used. As the solvent, dichloromethane, chloroform, tetrahydrofuran and the like can be used. As for reaction temperature, the temperature of about 20-50 degreeC is preferable. This is because the reaction rate is significantly slower than 20 ° C. and the formation of byproducts is increased above 50 ° C.

(B) preparing an amide compound represented by Scheme 1 (3) using ethylchloroformmate and a lipophilic compound from the 2,3-diacetyloxybenzoic acid compound produced in step (A):

The preparation of the amide compound of (3) in step (B) of the production method of the present invention can be both an acid halide, an active ester method, an acid anhydride method, but a high reaction yield and formation of by-products. Most preferred is a method of substituting an anhydrous state with a small amount of ethylchloroformmate, which is substituted with an amine having a lipophilic group to prepare compound (3). As for the equivalence ratio of the amine which has a lipophilic group reacted with the compound of said (2), 1: 1.0-1: 1.3 are preferable. If the equivalent ratio is less than 1: 1.0, the amount of the desired product is small, and if the ratio is greater than 1: 1.3, there is a problem in that purity and yield during purification are lowered due to unreacted amine.

In step (B) of the production method of the present invention, a base such as pyridine and triethylamine may be used. In step (B), as the reaction solvent, dichloromethane, chloroform, ethyl acetate, acetone, N, N-dimethylformamide, acetonitrile, tetrahydrofuran, and the like may be used. Preference is given to using N, N-dimethylformamide and tetrahydrofuran. On the other hand, the reaction temperature is preferably about 10 ~ 40 ℃. This is because the reaction rate is significantly slower than 10 ° C. and the formation of byproducts is increased above 40 ° C.

(C) hydrolyzing the acetyl group of the amide compound produced in step (B) to prepare a 2,3-dihydroxybenzoic acid derivative compound (compound 1):

In step (C) of the production method of the present invention, an alkali metal hydroxide such as sodium hydroxide and potassium hydroxide may be used. In step (C), the reaction solvent may be water, methanol, ethanol, propanol, tetrahydrofuran, dichloromethane, or the like, but a mixture of tetrahydrofuran and methanol may be used to complete the reaction in the fastest time.

Specific examples of the 2,3-dihydroxybenzoic acid derivative compound of the formula (1) obtained by the above production method are as follows.

N- (4-ethoxyphenyl) -2,3-dihydroxybenzamide.

N- (2-cyclohexenylethyl) -2,3-dihydroxybenzamide.

N-cycloheptyl-2,3-dihydroxybenzamide.

N-cyclohexyl-2,3-dihydroxybenzamide.

N- (tert-octyl) -2,3-dihydroxybenzamide.

N- (4-isopropylphenyl) -2,3-dihydroxybenzamide.

N- (2,3-dihydrobenzo [1,4] dioxin-7-yl) -2,3-dihydroxybenzamide.

N- (benzo [1,3] -dioxol-6-yl) -2,3-dihydroxybenzamide.

N- (adamantyl-1-yl) -2,3-dihydroxybenzamide.

The 2,3-dihydroxybenzoic acid derivative compound of the present invention prepared by the above process (Formula 1) may be contained as an active ingredient of the whitening cosmetic, the amount is 0.01 ~ of the total weight of the composition effective to cause a whitening action It is preferably contained in an amount of 20.0% by weight. The whitening cosmetic is not particularly limited in the formulation, specifically, softening longevity, astringent longevity, nourishing longevity, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, Cosmetic compositions such as powders, body lotions, body creams, body oils, body essences, makeup bases, foundations, hair dyes, shampoos, rinses or body cleansers; Or in pharmaceutical compositions such as ointments, gels, creams, patches or sprays. Each of these formulations may contain various bases and additives necessary and appropriate for the formulation of the formulation, and the types and amounts of these components can be easily selected by the inventors.

Hereinafter, the preparation method of the 2,3-dihydroxybenzoic acid derivative compound according to the present invention will be described in more detail with reference to Examples and Test Examples. However, the present invention is not limited by these Examples and Test Examples.

Example 1 N- (4-ethoxyphenyl) -2,3-dihydroxybenzamide

Dissolve 2,3-dihydroxybenzoic acid (100g, 0.65mol) in 1000ml of dichloromethane, add dimethylaminopyridine (catalyst amount 4g, 0.03mol) and reflux for 5 minutes, then triethylamine (199ml, 1.43mol) ) Was added dropwise. Acetic anhydride (135 ml, 1.43 mol) was slowly added dropwise thereto and refluxed at a reaction temperature of 40 ° C. for 2 hours. After completion of the reaction, dichloromethane (1000ml) was added dropwise to the reaction solution, diluted with 1000ml of water, washed with 500ml of 1M HCl solution, dried over anhydrous manganese (100g), filtered and concentrated to hexane. After crystallization, the mixture was refiltered to give 132 g (yield = 85%). This compound (100 g, 0.42 mol) was dissolved in tetrahydrofuran (1500 ml), triethylamine (76.1 ml, 0.55 mol) was added dropwise, and 1.3 equivalent of ethylchloroformmate (52.2 ml, 0.55 mol) was slowly added dropwise thereto. After stirring for 30 minutes, 4-ethoxyphenylamine (94.6g, 0.50mol) and triethylamine (84.3ml, 0.60ml) were dissolved in 1500ml of N, N-dimethylformamide and slowly added dropwise at 30 占 폚. After further stirring for 3 hours. After the reaction was completed, the mixture was filtered, the reaction solution was concentrated, dissolved in 1500 ml of dichloromethane, washed with distilled water (500 ml), washed with 500 ml of saturated sodium hydrogen carbonate, dried over anhydrous manganese (100 g), filtered and concentrated. Crystallized with hexane and refiltered to yield 107 g (yield = 88%). The compound (100 g, 0.27 mol) was dissolved in 1500 ml of a solvent of tetrahydrofuran and methanol (1: 1), 15% potassium hydroxide was added thereto, and 100 ml of the mixture was stirred for 30 minutes. After completion of the reaction, neutralize with acid, concentrate the reaction solution, add 1500 ml of ethyl acetate, dissolve and wash with 1000 ml of water, filter and concentrate to crystallize with hexane, re-filter and 68 g (yield = 88%) The desired product was obtained as a pale yellow solid.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.70

¹ H NMR (DMSO-d ₆ , δ): 11.42 (s, OH, 1H), 10.15 (s, NH, 1H), 9.27 (s, OH, 1H), 7.52 (d, 2H), 7.34 (d, 1H), 6.84 (t, 1H), 6.81 (d, 1H), 6.75 (d, 2H), 3.99 (q, 2H), 1.33 (t, 3H).

Example 2 N- (2-cyclohexenylethyl) -2,3-dihydroxybenzamide

The target product (65 g, 80% yield) was obtained as a pale yellow solid using the same method as Example 1 except for using 2-cyclohexenylethylamine instead of 4-ethoxyphenylamine.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.68

¹ H NMR (DMSO-d ₆ , δ): 11.73 (s, OH, 1H), 9.93 (s, NH, 1H), 9.17 (s, OH, 1H), 7.28 (d, 1H), 6.84 (t, 1H), 6.73 (d, 1H), 5.42 (s, 1H), 3.24 (m, 2H), 2.16 (m, 2H), 1.96 (m, 4H), 1.56 (m, 4H).

Example 3 N-cycloheptyl-2,3-dihydroxybenzamide

The target product (35 g, 85% yield) was obtained as a pale yellow solid using the same method as Example 1 except for using cycloheptylamine instead of 4-ethoxyphenylamine.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.58

¹ H NMR (DMSO-d ₆ , δ): 11.69 (s, OH, 1H), 10.11 (s, NH, 1H), 9.41 (s, OH, 1H), 7.35 (d, 1H), 6.85 (t, 1H), 6.79 (d, 1H), 3.97 (m, 1H), 1.85 (m, 2H), 1.55 (m, 10H).

Example 4 N-cyclohexyl-2,3-dihydroxybenzamide

The target product (62 g, 74% yield) was obtained as a pale yellow solid using the same method as Example 1 except for using cyclohexylamine instead of 4-ethoxyphenylamine.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.58

¹ H NMR (DMSO-d ₆ , δ): 11.67 (s, OH, 1H), 10.23 (s, NH, 1H), 9.42 (s, OH, 1H), 7.33 (d, 1H), 6.83 (t, 1H), 6.81 (d, 1H), 3.54 (m, 1H), 1.84 (m, 2H), 1.35-1.60 (m, 8H).

Example 5 N- (tert-octyl) -2,3-dihydroxybenzamide

Using the same method as in Example 1, except using tert-octylamine instead of 4-ethoxyphenylamine, the target product (64 g, 74% yield) was obtained as a pale yellow solid.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.61

¹ H NMR (DMSO-d ₆ , δ): 11.73 (s, OH, 1H), 10.23 (s, NH, 1H), 9.37 (s, OH, 1H), 7.33 (d, 1H), 6.85 (t, 1H), 6.82 (d, 1H), 1.35 (s, 6H), 1.43 (s, 2H), 1.06 (9H).

Example 6 N- (4-isopropylphenyl) -2,3-dihydroxybenzamide

The target product (78 g, 83% yield) was obtained as a pale yellow solid using the same method as Example 1 except for using 4-isopropylphenylamine instead of 4-ethoxyphenylamine.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.75

¹ H NMR (DMSO-d ₆ , δ): 11.35 (s, OH, 1H), 10.28 (s, NH, 1H), 9.38 (s, OH, 1H), 7.56 (d, 2H), 7.34 (d, 1H), 7.11 (d, 2H), 6.82 (t, 1H), 6.81 (d, 1H), 3.12 (m, 1H), 1.29 (d, 6H).

Example 7 N- (2,3-dihydrobenzo [1,4] dioxin-7-yl) -2,3-dihydroxybenzamide

Except for using 2,3-dihydrobenzo [1,4] dioxin-7-amine instead of 4-ethoxyphenylamine, using the same method as in Example 1 (68 g, 73% yield) Was obtained as a pale yellow solid.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.52

¹ H NMR (DMSO-d ₆ , δ): 11.23 (s, OH, 1H), 10.27 (s, NH, 1H), 9.37 (s, OH, 1H), 7.41 (d, 1H), 7.21 (s, 1H), 7.07 (d, 1H), 6.92 (m, 2H), 6.71 (t, 1H), 4.24 (m, 4H).

Example 8 N- (benzo [1,3] -dioxol-6-yl) -2,3-dihydroxybenzamide

The target product (70 g, 75% yield) was obtained as a pale yellow solid using the same method as Example 1 except for using benzo [1,3] -dioxol-6-amine instead of 4-ethoxyphenylamine. .

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.54

¹ H NMR (DMSO-d ₆ , δ): 11.73 (s, OH, 1H), 10.28 (s, NH, 1H), 9.37 (s, OH, 1H), 7.38 (d, 1H), 7.32 (s, 1H), 7.07 (d, 1H), 6.93 (m, 2H), 6.77 (t, 1H), 6.01 (s, 2H).

Example 9 N- (adamantyl-1-yl) -2,3-dihydroxybenzamide

Using the same method as in Example 1, except that adamantyl-1amine was used instead of 4-ethoxyphenylamine, the target product (80 g, 82% yield) was obtained as a pale yellow solid.

TLC (ethyl acetate: hexane = 1: 1) R _f = 0.57

¹ H NMR (DMSO-d ₆ , δ): 10.53 (s, OH, 1H), 9.24 (s, OH, 1H), 7.88 (s, 1H, NH), 7.26 (d, 1H), 6.83 (d, 1H), 6.57 (t, 1H), 2.08 (m, 9H), 1.66 (m, 6H).

[Test Example 1] melanin production inhibitory effect on melanocyte-producing cells

The degree of melanin production in cells of Examples 1 to 9 was measured by Dooley's method. The cell line was a Mel-Ab cell line derived from C57BL / 6 skin pigment cells. The culture was performed in DMEM medium containing 10% fetal placental serum, 100 nM 12-O-tetradecanoyl Phorbol-13-acetate, 1 nM Cholera Toxin, 37 ° C., 5% CO ₂ Under the conditions of. Cultured Mel-Ab cells were detached with 0.25% Trypsin-EDTA, plated on a 24-well vessel again with the same number (1 × 10 5 cells / well), and then 10 ppm for 3 consecutive days from the second day. The material was treated in a way that was replaced with a medium containing samples of. After 5 days, the melanin was dissolved in the cells by treatment with 1N NaOH, and the amount of melanin was measured by measuring absorbance at 400 nm. The results are shown in Table 1 below.

Inhibitory Effects of 2,3-Dihydroxybenzoic Acid Derivative Compounds on Melanin Production Test substance Melanin production rate (% control) Hydroquinone 11.46 Kojic acid 88.0 2,3-dihydroxybenzoic acid 78.5 Example 1 17.21 Example 2 18.71 Example 3 17.67 Example 4 15.27 Example 5 21.61 Example 6 18.97 Example 7 25.36 Example 8 14.23 Example 9 13.17

As a positive control, hydroquinone, kojic acid, and parent compound 2,3-dihydroxybenzoic acid were compared with the compounds of Examples 1 to 9 to measure melanin production inhibitory ability. As can be seen in Table 1, the compounds of Examples 1 to 9 showed a similar effect to hydroquinone. However, the effect of the parent 2,3-dihydroxybenzoic acid was very low. This shows that lipophilic plays an important role in exerting an effect.

Experimental Example 2 Cytotoxicity Confirmation Experiment of 2,3-Dihydroxybenzoic Acid Derivative Compound

Hydroquinone, a simple 2,3-dihydroxybenzoic acid derivative compound 2,3-dihydroxybenzoic acid, N-propyl 2,3-di in fibroblasts (Korea Cell Line Bank) incubated in a 96-well plate for 24 hours Hydroxybenzamide and the 2,3-dihydroxybenzoic acid derivative compounds of Examples 1 to 9 of the present invention having a specific lipophilic degree and molecular size were each added 100 ppm each, followed by incubation for 45 minutes, and then the supernatant was removed and the medium was 200 μl was injected and cultured again for 48 hours. After incubating for 4 hours by adding 50 µl of 5 mg / ml MTT reagent to the culture solution, the absorbance was measured at 540 nm using an ELISA reader. Cytotoxicity is expressed in% by the following formula. Cells cultured without any material were used as controls. The experimental results are shown in Table 2 below.

% Cell viability = {1- [comparative group absorbance (ODsub ₅₄₀ ) / control group absorbance (ODsub ₅₄₀ )]}

x 100

Cytotoxicity of 2,3-Dihydroxybenzoic Acid Derivative Compounds Test substance Cell survival rate (% control) Hydroquinone 10.1 Kojic acid 88.0 2,3-dihydroxybenzoic acid 31.1 N-propyl 2,3-dihydroxybenzamide 27.5 Example 1 87.0 Example 2 91.1 Example 3 94.7 Example 4 95.3 Example 5 90.9 Example 6 88.5 Example 7 93.1 Example 8 94.1 Example 9 86.3 Control 100.00

Examples of hydroquinone, kojic acid, and parent compound, 2,3-dihydroxybenzoic acid and general 2,3-dihydroxybenzoic acid derivatives, of which known whitening effects are known Cytotoxicity was measured in comparison with the compounds of 1-9. As can be seen in Table 2, the compounds of Examples 1 to 9 are very cytotoxic, unlike hydroquinone, 2,3-dihydroxybenzoic acid and N-propyl 2,3-dihydroxybenzamide compounds. It can be confirmed that it is a low substance.

Test Example 3 Whitening Effect Test on Human Skin

Twelve healthy men were attached with an opaque tape with a diameter of 1.5 cm in their upper arm and irradiated with UVB (1.5-2 times the minimum erythema of each subject) to induce skin blackening. . After irradiation, Examples 1-9 each 2% (solvent 1, 3 butylene glycol: ethanol = 7: 3), as a control, 2% hydroquinone, 2% kojic acid for 10 weeks, one place solvent I applied only (vehicle). Skin color was measured on a weekly basis with a colorimeter (Colorimeter CR-300, Minolta, Japan). The degree of brightness of the skin color is expressed as "ΔL (degree of increase of L value)", and the results are shown in Table 3 below.

Table 3 shows that the higher the value, the better the relative whitening effect.

Whitening Effect of 2,3-Dihydroxybenzoic Acid Derivatives on Human Skin Test substance Skin color brightness degree (ΔL) Vehicle -6.0 Hydroquinone -1.9 Kojic acid -3.0 Example 1 -2.6 Example 2 -2.5 Example 3 -2.0 Example 4 -1.9 Example 5 -2.4 Example 6 -2.2 Example 7 -2.3 Example 8 -1.8 Example 9 -1.5

In the experiment of confirming the whitening effect on the human skin of Table 3, in the case of Examples 1 to 9 it was confirmed that the whitening effect with the hydroquinone is very excellent.

 Formulation Example 1 Preparation of Nutritious Cosmetic Water (Milk Lotion)

Nutrients containing 2,3-dihydroxybenzoic acid derivative compounds prepared in Example 1 were prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Hyaluronic Acid Extract 5.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. 2,3-dihydroxybenzoic acid derivative Quantity 8. Caprylic Capric Triglycerides 8.0 9. Squalane 5.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Cetearyl Alcohol 1.0 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Triethanolamine 0.1

Formulation Example 2 Preparation of Nutritional Cream

A nourishing cream containing 2,3-dihydroxybenzoic acid derivative compound prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 3.0 3. Butylene Glycol 3.0 4. Liquid paraffin 7.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. 2,3-dihydroxybenzoic acid derivative Quantity 8. Caprylic Capric Triglycerides 3.0 9. Squalane 5.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Polysorbate 1.2 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Triethanolamine 0.1

Formulation Example 3 Preparation of Massage Cream

A massage cream containing 2,3-dihydroxybenzoic acid derivative compound prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Liquid paraffin 45.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. 2,3-dihydroxybenzoic acid derivative Quantity 8. Caprylic Capric Triglycerides 3.0 9. Beeswax 4.0 10. Cetearyl Glucoside 1.5 11.Sesqui oleic acid sorbitan 0.9 12. Vaseline 3.0 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Paraffin 1.5

Formulation Example 4 Preparation of Ointment

An ointment containing the 2,3-dihydroxybenzoic acid derivative compound prepared in Example 1 was prepared.

ingredient Content (% by weight) 1. Purified water To 100 2. Glycerin 8.0 3. Butylene Glycol 4.0 4. Liquid paraffin 15.0 5. Beta Glucan 7.0 6. Carbomer 0.1 7. 2,3-dihydroxybenzoic acid derivative Quantity 8. Caprylic Capric Triglycerides 3.0 9. Squalene 1.0 10. Cetearyl Glucoside 1.5 11.Sorbitan Stearate 0.4 12. Cetearyl Alcohol 1.0 13. Preservative Quantity 14. Incense Quantity 15. Coloring Quantity 16. Beeswax 4.0

As described above, the 2,3-dihydroxybenzoic acid derivative compound of the present invention has an effect of inhibiting melanin production, and the cosmetic composition containing the same can be realized as an effective whitening product by improving pigmentation of the skin. Can be. In addition, it is very cytotoxic and can be used safely on human skin.

Claims (3)

2,3-dihydroxybenzoic acid derivative compound represented by the following formula (1): [Formula 1]

In the above formula,

(A) reacting 2,3-dihydroxybenzoic acid and acetic anhydride in the presence of a base to prepare a 2,3-diacetyloxybenzoic acid compound (2); (B) preparing an amide compound (3) from the 2,3-diacetyloxybenzoic acid compound produced in step (A) using ethylchloroformmate and an amine having a lipophilic group; And (C) hydrolyzing the acetyl group of the amide compound of step (B) to prepare a 2,3-dihydroxybenzoic acid derivative compound (compound 1); Method for producing a 2,3-dihydroxy benzoic acid derivative compound represented by the following Scheme 1, comprising: Scheme 1

In Scheme 1, R is 4-ethoxyphenyl, 2-cyclohexenylethyl, cycloheptyl, cyclohexyl, tert-octyl, 4-isopropylphenyl, 2,3-dihydrobenzo [1,4] dioxine- 7-yl, benzo [1,3] -dioxol-6-yl or adamantyl-1-yl, In the step (B), the amine having a lipophilic group is 4-ethoxyphenylamine, 2-cyclohexenylethylamine, cycloheptylamine, cyclohexylamine, tert-octylamine, 4-isopropylphenylamine, 2,3- At least one amine selected from the group consisting of dihydrobenzo [1,4] dioxin-7-amine, benzo [1,3] -dioxol-6-amine and adamantyl-1amine. A cosmetic composition comprising 0.01 to 20% by weight of the 2,3-dihydroxybenzoic acid derivative compound according to claim 1.