KR100775095B1 - Whitening composition for external applications to the skin containing tyrosol derivatives - Google Patents

Abstract

A skin external composition for whitening skin containing tyrosol derivatives is provided to suppress pigment permeation, improve spots and freckles, and whiten the skin by inhibiting melanin formation without side effects. A skin external composition for whitening skin contains 0.001-10 wt.% of tyrosol derivatives represented by the formula(1), wherein Ar1 is the structural formula(1-a), Ar2 is the structural formula(1-b), m is an integer of 1 or 2 and n is an integer of 2 or 3, and is formulated as soft lotion, astringent lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, gel, pack, powder, body lotion, body cream, body oil or body essence.

Description

Whitening composition for external applications to the skin containing tyrosol derivatives}

The present invention relates to a cosmetic composition for skin whitening having an excellent whitening effect without the side effects by containing a tyrosol derivative of the general formula (1) as an active ingredient.

[Formula 1]

이고, Ar₂는

이며, k는 0 내지 2의 정수, m은 1 내지 2의 정수, n은 2 내지 3의 정수이다.)Where Ar ₁ is

And Ar ₂ is

K is an integer of 0 to 2, m is an integer of 1 to 2, n is an integer of 2 to 3)

Human skin color is determined by a number of factors, including the activity of melanocytes that make melanin, the distribution of blood vessels, the thickness of the skin, and the presence or absence of pigments inside and outside the body, such as carotenoids and bilirubin. The most important is a black pigment called melanin produced by the action of various enzymes such as cinnases. The formation of melanin pigment is influenced by genetic factors, physiological factors related to hormone secretion, stress, and environmental factors such as ultraviolet irradiation. Melanin is present in the skin and has an important function of protecting the body from ultraviolet rays, but it is known that melanin is overproduced to form spots, freckles, etc., promote skin aging, and also play an important role in inducing skin cancer.

Ascorbic acid, kojic acid, arbutin, hydroquinone, glutathione or derivatives thereof to treat or alleviate excessive melanin pigmentation caused by skin pigmentation abnormalities such as blemishes, freckles and pigmentation and UV exposure. In addition, substances having tyrosinase inhibitory activity have been used in cosmetics and pharmaceuticals, but their use is limited due to insufficient whitening effects, safety problems for skin, formulation and stability problems when formulated in cosmetics, and the like.

It is not only excellent in safety but also can show various effects through synthesis of derivatives for natural-derived active substances. Therefore, it is a good search target for whitening substances. Therefore, it is natural-derived with both excellent whitening effect and safety for human skin. Efforts to research potent substances through active substance derivatives continue.

Recent structural analysis of phenolic compounds derived from Hong Kyung-cheon by Mary Ann Lila (Phytochemistry. 2006 67 (21): 2380-91) and Dong Sheng Ming (Phytother Res. 2005 19 (9): 740-3) And para-tyrosol. In addition, prior patents (US20030180833, US2003 / 0108651) exist for inhibiting melanogenesis of hydroxytyrosol derived from natural olive oil. Pharmacologically important ingredients in Rhodiola saline are known as salidroside and p-tyrosol. They are effective for arthritis, pain, pulmonary tuberculosis, anemia, neuralgia, hepatitis and hypotension. Hematopoietic, cold-resistant, anti-inflammatory action is more effective than ginseng, but has the advantage of no side effects of ginseng. Among the components, p-tyrosol is known to be excellent in antioxidant and anti-inflammatory activity by itself. However, there is a problem in that the tyrosol or hydroxytyrosol derived from nature does not exhibit a sufficiently good effect in terms of the whitening effect.

Therefore, it is necessary to develop a skin whitening cosmetic that exhibits excellent whitening effect without skin side effects by derivatizing a compound having a new structure.

Naturally derived tyrosol or hydroxytyrosol is a compound having safety on human skin and is known to have a whitening effect, but the material itself has a problem of insignificant whitening effect.

Therefore, it is an object of the present invention to provide a cosmetic for whitening skin having excellent whitening effect without side effects by containing a new tyrosol derivative that can be used safely on the human skin as well as excellent whitening effect as an active ingredient.

The present inventors studied a new whitening agent having excellent whitening effect and safety for human skin. As a result, a new structure of a tyrosol derivative prepared by esterification with a carboxylic acid having a hydroxyphenyl group was obtained. The present invention has been found to have excellent pigmentation inhibitory effect as well as excellent safety for human skin.

The present invention provides a cosmetic for skin whitening containing a tyrosol derivative represented by the following formula (1) as an active ingredient.

[Formula 1]

이고, Ar₂는

이며, k는 0 내지 2의 정수, m은 1 내지 2의 정수, n은 2 내지 3의 정수이다.)Where Ar ₁ is

And Ar ₂ is

K is an integer of 0 to 2, m is an integer of 1 to 2, n is an integer of 2 to 3)

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

The tyrosol derivative contained as an active ingredient in the skin whitening cosmetics according to the present invention has a structure represented by the following Chemical Formula 1.

 [Formula 1]

이고, Ar₂는

이며, k는 0 내지 2의 정수, m은 1 내지 2의 정수, n은 2 내지 3의 정수이다.)Where Ar ₁ is

And Ar ₂ is

K is an integer of 0 to 2, m is an integer of 1 to 2, n is an integer of 2 to 3)

More preferably Ar ₁ in Formula 1 is selected from the following substituents,

Ar ₂ is selected from the following substituents.

In addition, the tyrosol derivative of Formula 1 includes a compound of the following structural formula.

The tyrosol derivative may be prepared by the preparation method shown in Scheme 1 below. Reaction Scheme 1 below is a method of preparing a tyrosol derivative of Chemical Formula 1 by esterification of an alcohol compound and a carboxylic acid compound, and as the esterification reagent, dicyclohexylcarbodiimide (DCC) may be used.

Scheme 1

(Wherein Ar ₁ , Ar ₂ and k are as defined in Formula 1)

However, it is not limited to the above production method and may be variously prepared using a known organic synthesis reaction.

It is not necessary to limit the content of the tyrosol derivative of Formula 1, but 0.001 to 20% by weight, more preferably 0.001 to 10% by weight, even more preferably 0.01 to 5% by weight based on the total weight of the cosmetic composition It is good to contain. This is because the effect can not be expected at less than 0.001% by weight, there is a difficulty in the safety or formulation formulation over 20% by weight.

In addition, the cosmetic composition for skin whitening of the present invention, in addition to the tyrosol derivative, preferably contains other whitening ingredients and the like that can give a synergistic effect to the whitening effect within a range that does not impair the whitening effect of the present invention. It is okay to do it. Arbutin, an ascorbic acid derivative, etc. are mentioned as such a whitening component.

In addition, the whitening cosmetic of the present invention is not particularly limited in the formulation, for example, supple cosmetics, astringent cosmetics, nourishing cosmetics, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, It may be formulated into a cosmetic such as cleansing water, gel, pack, powder, body lotion, body cream, body oil, body essence and the like.

Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to Examples and Test Examples, but the scope of the present invention is not limited by the following Examples.

Preparation Example 1 Synthesis of 2-hydroxyphenethyl 3,4,5-trihydroxybenzoate

Dissolve gallic acid (0.02mol) and 2-hydroxyphenethyl alcohol (0.025mol) in 20mL THF. The solution is placed in a flask equipped with a CaCl ₂ filled tube. After mounting the ice bath DCC solution (DCC 0.02mol / CH ₂ Cl ₂ 10mL) was slowly added. After removing the ice bath, the reaction was stirred at room temperature for 5 hours. After completion of the reaction, the reaction was filtered to remove urea. The filtrate was washed several times with water and further with 5% acetic acid. Washed again with water, dried over MgSO ₄ and the solvent was removed. The reaction was separated by silica gel column chromatography and dried. The product was washed with chloroform and then filtered and dried to obtain an ivory 2-hydroxyphenethyl 3,4,5-trihydroxybenzoate (1.5095 g, yield: 26%).

¹ H NMR (Acetone-d ₆ , δ): 8.21 (s, OH, 4H), 7.22 (s, Ar, 1H), 7.06 (s, Ar, 2H), 6.83 (m, Ar, 2H), 6.78 ( d, Ar, 2H), 4.43 (t, 2H), 3.02 (t, 2H).

Preparation Example 2 Synthesis of 3-hydroxyphenethyl 3,4,5-trihydroxybenzoate

Ivory 3-hydroxyphenethyl 3,4,5-trihydroxy was prepared in the same manner as in Example 1 except using 3-hydroxyphenethyl alcohol (0.025 mol). 1.655 g (yield: 28.5%) of benzoate were obtained.

¹ H NMR (Acetone-d ₆ , δ): 8.26 (s, OH, 4H), 7.08 (s, Ar, 1H), 7.01 (s, Ar, 2H), 6.83 (m, Ar, 1H), 6.67 ( d, Ar, 2H), 4.36 (t, 2H), 2.97 (t, 2H).

[Test Example 1]

B16 / F10 Melanoma The melanoma cell  Melanin production Inhibitory ability  evaluation

Using the tyrosol derivatives prepared in Preparation Examples 1 and 2 as test substance, 2 X 10 ⁴ cells / well (final volume) in a 6-well plate (melanin quantitative determination) with DMEM containing 10% FBS. 3 ml), in a 96-well plate (MTT assay) in 2 X 10 ³ cell / well (final volume 200 ul) and 37 ℃, 5% CO ₂ incubator (MCO-20AIC, Incubate for 24 hours in Sanyo. After incubation, remove the medium and use DMEM medium containing 10% FBS, 2 uM α-MSH (Melanocyte stimulating hormone), 2 mM theophylline as a fresh medium and add test substances to the medium for 3 days every day. Process. On day 5, cultured medium was removed from a 6-well plate and treated with 0.25% trypsin-EDTA (Sigma Chemical Co.) solution to recover the cell pellet and 1.5 ml. Transfer to a tube (centrifuge) at 10,000 rpm for 10 minutes to remove the supernatant. After drying the pellet obtained at 60 ℃ 100N of 1N NaOH to dissolve the intracellular melanin. Dilute this solution with PBS and measure the absorbance at 475 nm of ELISA reader to determine the rate of melanin inhibition in the sample. As a control, the cells without addition of the tyrosol derivative were measured for the whitening effect by measuring the degree of inhibition of melanin production of the test substance compared with the melanin content in the control. According to Equation 1 below to calculate the melanin production inhibition is shown in Table 1 the results.

Equation 1

[Table 1] Melanin production inhibitory effect

As can be seen from Table 1, the compounds of Examples 1 and 2 according to the present invention can be seen that the whitening effect is superior to the case of para-tyrosol (p-tyrozol) and koji acid. .

On the other hand, the formulation of the skin whitening cosmetics containing the tyrosol derivative of the present invention can be arbitrarily selected, and can be prepared in various forms, such as nutrition cream, nutrition lotion, massage cream, nutrition essence, supple cosmetics which are conventional cosmetic formulations. Can be. Polysorbate used in the following formulation was manufactured by Uniquema, polyacrylic acid was used SNF product name Flogel 700, polyvinyl alcohol was used Kuraray (Kuraray) PVA-217.

Formulation Example 1 Nutritious Longevity (Milk Lotion)

As shown in Table 2, nutrient-containing longevity containing a tyrosol derivative was prepared according to a conventional method.

TABLE 2

Formulation Example 2 Softener (Skin Lotion)

A flexible longevity containing a tyrosol derivative was prepared according to a conventional method as shown in Table 3 below.

TABLE 3

Formulation Example 3 Nutrition Cream

A nutritive cream containing a tyrosol derivative was prepared according to a conventional method as shown in Table 4 below.

TABLE 4

Formulation Example 4 Massage Cream

A massage cream containing a tyrosol derivative was prepared according to a conventional method as shown in Table 5 below.

TABLE 5

[Formulation Example 5] Pack

A pack containing a tyrosol derivative was prepared according to a conventional method as shown in Table 6 below.

TABLE 6

Formulation Example 6 Gel

As shown in Table 7 below, a gel containing a tyrosol derivative was prepared according to a conventional method.

TABLE 7

As described above, the skin whitening cosmetics using the tyrosol derivative provided by the present invention as an active ingredient have safety against human skin and provide excellent whitening effects.

Claims (5)

Cosmetics for skin whitening containing a tyrosol derivative represented by the following formula (1) as an active ingredient. [Formula 1]

Where Ar ₁ is

And Ar ₂ is

M is an integer of 1 to 2, n is an integer of 2 to 3.) The method of claim 1, Ar ₁ is selected from the following substituents,

Ar ₂ is selected from the following substituents

Cosmetics for skin whitening, characterized in that. The method of claim 2, Cosmetics for skin whitening, characterized in that selected from the following structural formula.

The method of claim 1, The content of the tyrosol derivative is a skin whitening cosmetic, characterized in that 0.001 to 10% by weight relative to the total weight of the cosmetic. The method of claim 1, The cosmetics may include softening cream, astringent makeup, nutrition cream, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, gel, pack, powder, body lotion, body cream, body oil or A cosmetic for skin whitening, characterized in that the formulation is selected from body essences.