KR102160306B1 - skin whitening agent - Google Patents

Abstract

The present invention relates to a composition for skin whitening containing 1,3-diethoxybenzene having excellent whitening activity as an active ingredient, and has excellent skin whitening effect and excellent safety because no side effects occur.

Description

Skin whitening agent

The present invention relates to a cosmetic composition for skin whitening containing 1,3-diethoxybenzene as an active ingredient, and more particularly, it can be safely used without side effects on the skin, and has a melanin production inhibitory effect. It relates to an excellent skin whitening composition.

The skin is the largest tissue in the human body and plays an important role in protecting the inside of the skin from external stimuli as the primary barrier. These skins appear differently in color depending on the person or with age, which is determined by the concentration and distribution of melanin in the skin. Skin darkening (melanogenesis) is a defense mechanism against stimuli such as ultraviolet rays in melanocytes, and the activity of melanin production is increased. It is the result. Although melanin has a protective effect on the skin, hyperpigmentation of the skin causes spots, freckles, skin darkening after skin inflammation, and senile pigment spots. This causes not only cosmetic discomfort to the person concerned, but also negative mental effects, causing discomfort in social activities. It also causes. The melanin production process is made through a non-enzymatic oxidation reaction after an enzyme called tyrosinase acts on tyrosine, a type of amino acid, and is converted into dopa and dopaquinone. It is known that spots and age spots occur.

Various compositions have been conventionally used to suppress melanin production in the skin as described above. For example, various extracts extracted from L-ascorbic acid and its derivatives, hydroquinone, arbutin and licorice, and upper bark are used as skin whitening agents. However, L-ascorbic acid is easily oxidized and causes irritation to the skin, and cosmetics formulated with it cause problems of discoloration and discoloration, and substances derived from plant extracts have severe differences in efficacy depending on the origin of the plant, thus maintaining the homogeneity of the product. It is difficult to become, and arbutin has a disadvantage of low effectiveness.

In order to solve the above problems, the present invention provides a cosmetic composition containing 1,3-diethoxybenzene as an active ingredient that has no side effects on the skin and has a melanin production inhibitory effect.

The present invention provides a cosmetic composition comprising a compound represented by the following formula (1) as an active ingredient, which has excellent melanin production inhibitory effect.

Formula 1

The present invention provides a skin whitening composition containing the compound represented by Formula 1 as an active ingredient.

The cosmetic composition of the present invention has an excellent whitening effect, and since there is little skin irritation to the human body, the safety of the product is excellent, so it can be usefully used as a cosmetic composition for skin whitening.

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

The present invention provides a composition for skin whitening comprising the compound represented by Formula 1 as an active ingredient.

The compound has excellent whitening effect by inhibiting melanin production. Therefore, the compound is useful as a cosmetic composition for skin whitening. In addition, the cosmetic composition of the present invention is safe for human skin because it does not show a distinct pattern in the skin cumulative irritation test.

The compounds can be obtained through a synthetic process by a conventional method.

The content of the compounds and/or mixtures thereof contained in the preparation of an ointment for external use or cosmetics is 0.00001 to 10.0% by weight, preferably 0.001 to 1.0% by weight, based on the total amount of the composition. If the content of the compound and/or a mixture thereof is less than 0.00001% by weight based on the total amount of the composition, a distinct effect such as skin whitening cannot be expected, and if it exceeds 10.0% by weight, a distinct effect increases with increasing content. Did not appear.

Ingredients included in the cosmetic composition of the present invention include ingredients commonly used in cosmetic compositions in addition to the above compounds and/or mixtures thereof as active ingredients, such as antioxidants, stabilizers, solubilizers, vitamins, pigments and fragrances, and Such conventional adjuvants, and carriers.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , Oil, powder foundation, emulsion foundation, wax foundation, spray, etc. may be formulated, but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, astringent lotion, a nutrition lotion, a nutrition cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide may be used as carrier components. I can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additionally chlorofluorohydrocarbon, propane / May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, liquid diluents such as water, ethanol or propylene glycol as carrier components, ethoxylated isostearyl alcohol, suspending agents such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, crystallites Sex cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like can be used.

When the formulation of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters may be used.

Example One

1,3- Of diethoxybenzene (1,3-diethoxybenzene) Produce

1,3-dihydroxybenzene (220 mg) was dissolved in 20 mL of a dimethylformamide solution, and then 800 mg of potassium carbonate (K2CO3) was added dropwise. After stirring for 10 minutes, 880 mg of bromoethane was added dropwise, followed by stirring for 24 hours. 40 ml of purified water was poured and dried over magnesium sulfate extracted with ethyl acetate. The residue obtained by distillation under reduced pressure was subjected to column chromatography using a mixed solvent of hexane and ethyl acetate as a developing solvent to obtain 322 mg of liquid 1,3-diethoxybenzene.

FAB mass: 167.2 [M+H] ⁺

Experimental example One

Melanogenesis inhibition effect test at the cellular level

1,3-diethoxybenzene was added to the culture medium of mouse melanoma cells (B-16 mouse melanoma cells) to test the whitening effect at the cellular level as follows (Lotan R., Lotan D. Cancer Res. 40 :3345-3350, 1980).

Each compound was added to the culture solution when culturing B-16 melanoma cells at a final concentration of 1 μg/ml and 10 μg/ml, respectively, and after incubating for 3 days, the cells were treated with trypsin, and the culture vessel After peeling from and centrifuging, melanin was extracted. Add 1 ml of sodium hydroxide solution (1N concentration) to the extracted melanin, boil for about 10 minutes to dissolve the melanin, and measure the absorbance at 400 nanometers (nm) with a spectrophotometer to determine the amount of melanin produced per unit cell count (10 ⁶ cell) was carried out by the method of indicating the absorbance. This experiment was repeated three times, and the average value was used to calculate the relative amount of melanin production relative to the control group as the inhibition rate (%), and the results are shown in Table 1 below.

sample Concentration (㎍/ml) Inhibition rate (%) Control (no addition) - 0 1,3-diethoxybenzene One 25 10 74 Hydroquinone One 43 10 Cell death

Repetitions = 3

As shown in Table 1, it can be seen that 1,3-diethoxybenzene has a comparable ability to inhibit melanin production with respect to cultured mouse melanoma cells compared to hydroquinone, which is a conventional whitening substance. In addition, hydroquinone has a strong ability to inhibit melanin production at low concentrations, but it is not possible to test above 10 ㎍/ml due to severe cytotoxicity, but quinic acid derivatives do not show cytotoxicity and have a higher inhibitory effect on melanogenesis than hydroquinone. This indicated that the present invention can be very usefully used for improving spots and freckles and for skin whitening.

Manufacturing example 1 and Comparative example One

The ointment for external use of the skin was prepared by mixing as shown in Table 2 below.

Composition weight% Manufacturing Example 1 Comparative Example 1 1,3-diethoxybenzene
Diethyl sebacate
Abiding
Polyoxyethylene oleyl ether phosphate
Sodium benzoate
vaseline 0.01
8
5
6
Appropriate amount
Balance* -
8
5
6
Appropriate amount
Balance*

*: Amount to make the whole 100% by weight

Manufacturing example 2 and Comparative example 2

A nourishing cream was prepared by mixing as shown in Table 3 below.

Composition weight% Manufacturing Example 2 Comparative Example 2 1,3-diethoxybenzene
Stearic acid
Cetanol
PEG-20 Sovitan Monostearate
Sorbitan monostearate
Mineral oil
Trioctanoate
Triethanolamine
Carbomer
glycerin
Propylene glycol
antiseptic
incense
Purified water 0.01
1.0
2.0
1.0
1.0
10.0
5.0
0.5
0.2
5.0
3.0
Appropriate amount
Appropriate amount
Balance* -
1.0
2.0
1.0
1.0
10.0
5.0
0.5
0.2
5.0
3.0
Appropriate amount
Appropriate amount
Balance*

*: Amount to make the whole 100% by weight

Manufacturing example 3 and Comparative example 3

A flexible lotion was prepared by mixing according to the ratio shown in Table 4 below.

Composition weight% Manufacturing Example 3 Comparative Example 3 1,3-diethoxybenzene
ethanol
Polyoxyethylene hardened castor oil
Paraoxybenzoic acid methyl
glycerin
1,3-butylene glycol
incense
Pigment
Purified water 0.01
10.0
1.0
2
5.0
6.0
Appropriate amount
Appropriate amount
Balance* -
10.0
1.0
2
5.0
6.0
Appropriate amount
Appropriate amount
Balance*

*: Amount to make the whole 100% by weight

Manufacturing example 4 and Comparative example 4

Essence was prepared by mixing as shown in Table 5 below.

Composition weight% Manufacturing Example 4 Comparative Example 4 1,3-diethoxybenzene
Propylene glycol
glycerin
Sodium hyaluronate aqueous solution (1%)
ethanol
Polyoxyethylene hardened castor oil
Paraoxybenzoic acid methyl
Carbomer
Triethanolamine
incense
Purified water 0.01
10.0
10.0
5.0
5.0
1.0
0.1
0.3
0.4
Appropriate amount
Balance* -
10.0
10.0
15.0
5.0
1.0
0.1
0.3
0.4
Appropriate amount
Balance*

*: Amount to make the whole 100% by weight

Manufacturing example 5 and Comparative example 5

A pack was prepared by mixing according to the ratio shown in Table 6 below.

Composition weight% Manufacturing Example 5 Comparative Example 5 1,3-diethoxybenzene
glycerin
Propylene glycol
Polyvinyl alcohol
ethanol
Polyoxyethylene hardened castor oil
Polyoxyethylene oleyl ethyl
Paraoxybenzoic acid methyl
incense
Pigment
Purified water 0.01
5.0
4.0
15.0
8.0
1.0
1.0
0.2
Appropriate amount
Appropriate amount
Balance* -
5.0
4.0
15.0
8.0
1.0
1.0
0.2
Appropriate amount
Appropriate amount
Balance*

*: Amount to make the whole 100% by weight

Manufacturing example 6 and Comparative example 6

A nutrient lotion was prepared by mixing according to the ratio shown in Table 7 below.

Composition weight% Manufacturing Example 6 Comparative Example 6 1,3-diethoxybenzene
Polyoxyethylene hardened castor oil
Paraoxybenzoic acid methyl
glycerin
1,3-butylene glycol
Carbomer
Triethanolamine
Propylene glycol
ethanol
Carboxyvinyl polymer
Pigment
incense
Purified water 0.01
1.0
Appropriate amount
6.0
5.0
0.2
0.3
5.0
2
One
Appropriate amount
Appropriate amount
Balance* -
1.0
Appropriate amount
6.0
5.0
0.2
0.3
5.0
3.2
0.1
Appropriate amount
Appropriate amount
Balance*

*: Amount to make the whole 100% by weight

Experimental example 3

Whitening effect test in clinical

20 healthy men and women were selected as test subjects, covered with aluminum foil with 4 holes each with a diameter of 7 mm on the lower arm of both arms, and then 60 mJ with a sunlight irradiator (ORIEL Solar Simulator 1000W) at a distance of 10 cm from the arm. The amount of light of /cm2 was irradiated. The bases prepared according to Preparation Example 4 and Comparative Example 4 were applied twice a day from 3 days before irradiation to 3 weeks after irradiation in a pair on the same line. For each of the above, the degree of pigmentation in Preparation Example and Comparative Example was visually determined, and the results are shown in Table 8 below.

Test substance Distinct effect (persons) Effective (persons) No difference (persons) Manufacturing Example 4 3 10 7 Comparative Example 4 - 2 18

As shown in Table 8 above, the essence prepared according to Preparation 4 exhibited a whitening effect for at least 13 or more of 20 test subjects, and also did not show any side effects in the skin, so it is safe and effective in improving spots and freckles. It can be seen that it is a skin whitening agent with excellent effects.

Claims (4)

delete Skin external pharmaceutical composition for the prevention, treatment and whitening of hyperpigmentation, spots, freckles and age spots containing 1,3-diethoxybenzene or a pharmacologically acceptable salt thereof as an active ingredient The method of claim 2,
Prevention, treatment and whitening of hyperpigmentation, spots, freckles and age spots containing 0.00001 to 10.0% by weight of 1,3-diethoxybenzene or a pharmacologically acceptable salt thereof based on the total amount of the composition Skin external pharmaceutical composition The method of claim 2, wherein the composition is formed in any one formulation selected from the group consisting of skin, lotion, cream, foundation, essence, gel, pack, pumice cleansing, and ointment. For the prevention, treatment and whitening of skin external pharmaceutical composition.