KR101832415B1 - Cosmetic composition for skin whitening comprising retinoids derivative as active ingredient - Google Patents

Abstract

The present invention provides a skin whitening cosmetic composition containing a retinoid derivative as an active ingredient. The retinoid derivatives of the present invention are excellent in an effect of suppressing tyrosinase activity and an effect of inhibiting melanin synthesis, and can be usefully used as a cosmetic composition for skin whitening.

Description

TECHNICAL FIELD The present invention relates to a skin whitening cosmetic composition containing a retinoid derivative as an active ingredient. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cosmetic composition for skin whitening,

The present invention relates to a cosmetic composition for skin whitening comprising a retinoid derivative as an active ingredient.

Skin is a very important tissue with direct contact with the external environment and has a biochemical and physical function. It is divided into three parts: epidermis, dermis, and hypodermis.

Melanin is a pigment present in the epidermis of the skin. It is made from melanocytes in the basal layer of the epidermis and migrates to epidermal cells called keratinocytes. In vivo, there is no enzymes that degrade melanin, but keratinocytes are removed from the skin as they fall off the epidermis.

In melanosome synthesis, tyrosine is first converted to dopaquinone via dopase (DOPA) by an enzyme called tyrosinase in the melanosome called ERA in melanocytes, and then by autoxidation and enzymatic reaction from dopaquinone Melanin, which is a dark brown copolymer, is produced through dopachrome. The resulting melanin is transferred to the keratinocyte through melanoma, and after about 28 days of keratinization, it exits the skin surface and disappears with the keratinocytes.

Melanin absorbs the light energy of sunlight UV and protects the subcutaneous skin organs from UV damage. It also helps protect the skin from external harmful factors such as harmful oxygen and free radicals generated in the skin. Role. In addition, the skin color of a person is determined according to the amount of melanin in the skin cells.

People with high melanin pigment have brown or black skin while those with low melanin pigment have white skin. However, abnormal production of melanin causes skin lesions such as vitiligo. On the other hand, when melanin is not completely eliminated due to excessive synthesis of melanin due to sunlight, hormonal changes, inflammation, give. In addition, pigmentation of the skin is deposited, forming spots and freckles, and it also causes skin cancer from such lesions. Therefore, in order to prevent such pigment deposition phenomenon, it is necessary to inhibit a part of the melanin production process to reduce the production of melanin.

Currently, in the development of a whitening agent for skin cosmetics, there is known a method of decolorizing by reducing the produced melanin pigment and a method of inhibiting the activity of tyrosinase, an enzyme that forms a melanin pigment. However, it is known that the whitening agent using tocopherol, vitamins and the like, which is used for reducing the melanin pigment, has little discoloration effect of the melanin pigment. Accordingly, inhibitors that inhibit the production of melanin pigment by attenuating the activity of tyrosinase have been attracting attention.

In the field of the conventional cosmetics, as a whitening component, for example, substances inhibiting tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, L-ascorbic acid, Derivatives thereof and various plant extracts have been used.

However, the use thereof is limited due to poor stability and coloration, generation of odor, efficacy at a living body level, unclear effect, and safety problem. Kojisan inhibits the enzyme activity by adsorbing copper ions present in the active site of tyrosinase, but when used in cosmetics, instability, problems of skin side effects, and recent animal tests have revealed that liver cancer has been caused and the use of cosmetic ingredients has been discontinued. Vitamin-C and its derivatives are difficult to use as a raw material for cosmetics because of its good oxidative instability. Hydroquinone has excellent whitening effect on skin, but it has allergic properties, toxicity to melanin-producing cells, permanent decolorization to skin It is highly irritating to the skin. It has recently been prescribed as a carcinogenic substance and its use is prohibited.

In addition, arbutin is a derivative in which hydroquinone is conjugated with glucopyranoside. As a result, hydroquinone is less toxic to human body, and inhibits the synthesis of melanin pigment, resulting in an increase in melanin pigmentation However, it is disadvantageous in that it is partially decomposed by skin enzymes. Therefore, it is urgent to develop a whitening agent that is more effective than the whitening agent so far and more safe.

On the other hand, retinoids (vitamin A) are well known as cosmetics for skin aging and skin wrinkle improvement. The main retinoids are retinol (Vitamin A alcohol), retinal (Vitamin A aldehyde), retinyl ester Retinyl acetate, retinyl propionate, retinyl linoleate, and retinyl palmitate, which are one kind, are available.

The present invention relates to a novel retinoid derivative which is developed for solving such problems as skin irritation and instability of a retinoid. Korean Patent Registration No. 10-0556037 discloses a novel retinoid derivative which is effective for promoting collagen synthesis, antioxidation, inhibition of tyrosinase activity, A retinol derivative having a wrinkle-improving effect is proposed.

Korean Patent Registration No. 10-0556037

The present inventors have made efforts to provide a novel whitening agent exhibiting excellent whitening effect and no side effect, and as a result, found that a novel retinoid derivative can inhibit the activity of tyrosinase and effectively inhibit melanin production, and have completed the present invention.

The present invention provides a cosmetic composition for skin whitening which is capable of inhibiting tyrosinase involved in the skin darkening process and inhibiting melanin production and having an excellent skin whitening effect.

To this end, the present invention provides a cosmetic composition for skin whitening comprising a retinoid derivative represented by the following formula (1) as an active ingredient:

[Chemical Formula 1]

(Wherein,

R ₁ and R ₂ are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.

Since the retinoid derivative according to the present invention effectively inhibits melanin synthesis inhibition and tyrosinase activity, the cosmetic composition containing the same as an effective ingredient is very useful for improvement of spots, freckles and skin whitening.

1 is a graph showing the amount of melanin produced according to the concentration of 1,5-bis-retinamido 2-methylpentane treatment according to an embodiment of the present invention.
2 is a graph showing tyrosinase activity according to 1,5-bis-retinamido 2-methylpentane treatment concentration according to an embodiment of the present invention.

Hereinafter, the present invention will be described in detail.

The retinoid derivative contained as an active ingredient in the cosmetic composition for skin whitening according to the present invention has a structure represented by the following formula (1).

[Chemical Formula 1]

(Wherein,

R ₁ and R ₂ are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.

More preferably, R ₁ in the general formula ( ₁₎ is a methyl group and R ₂ is Hydrogen.

The retinoid derivatives of Formula 1 according to the present invention can be prepared according to the methods described below.

As a first preparation method, a compound of formula (2) wherein Y is hydroxy can be reacted with a compound of formula (3) in the presence of a condensing agent and an organic amine catalyst in a solvent to obtain a retinoid derivative.

(2)

(3)

(Wherein,

Y is hydroxy or halogen,

R ₁ and R ₂ are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms.

N, N ', N'-tetramethyl- (benzotriazol-1-yl) -uronium tetrafluoroborate (TBTU) and N- (3-dimethylaminopropyl) -N' But are not limited to, ethyl-carbodiimide (EDC), N, N'-diisopropylcarbodiimide (DIC) or N, N'-dicyclohexylcarbodiimide (DCC).

As the organic amine catalyst for promoting the condensation reaction, diisopropylethylamine (DIPEA) or 4-dimethylaminopyridine (DMAP) may be used, but the present invention is not limited thereto. As the solvent, at least one selected from anhydrous organic solvents such as dichloromethane, benzene, toluene, tetrahydrofuran and diethyl ether may be used, but the present invention is not limited thereto. The reaction is preferably carried out in a state where light and moisture are blocked under a nitrogen atmosphere, and the reaction may proceed in a cooled or warmed state.

Alternatively, the compound of formula (2) wherein Y is halogen can be prepared by reacting the compound of formula (3) in the presence of an organic amine in a solvent.

In this case, pyridine or triethylamine may be used as the organic amine serving as the base, but the present invention is not limited thereto. As the solvent, at least one selected from anhydrous organic solvents such as dichloromethane, benzene, toluene, tetrahydrofuran and diethyl ether may be used, but the present invention is not limited thereto. At this time, the organic amine is preferably used in an amount of 1.0 to 2.0 equivalents based on the compound of formula (3). The reaction is preferably carried out in a state where light and moisture are blocked under a nitrogen atmosphere, and the reaction may proceed in a cooled or warmed state.

Compounds of formula (2) wherein Y is a halogen, used as a starting material, can be prepared by reacting retinoic acid with a halogenating agent such as phosphorus trichloride, thionyl chloride and oxalyl chloride.

The compound of formula (I) prepared by the above method can be isolated and purified by conventional separation and purification methods, for example, recrystallization or column chromatography.

In the composition of the present invention, the content of the retinoid derivative is 0.0001 to 10% by weight, preferably 0.01 to 5.0% by weight, based on the total weight of the cosmetic composition. The content of the extract is preferably at least the above-mentioned minimum value so as to achieve a minimum skin whitening effect, and it is preferable that the content of the extract is below the maximum value in consideration of the deterioration of use feeling due to the excessive addition and applicability to various formulations. At this time, it is preferable that the content of the retinoid derivative is appropriately adjusted within the above-described range according to the content of the components contained in the formulation or cosmetic composition.

In addition, the cosmetic composition for whitening skin of the present invention may contain other whitening components or the like which can give a synergistic effect to the whitening effect within a range that does not impair the desired whitening effect of the present invention in addition to the retinoid derivatives It is acceptable. Examples of such whitening components include arbutin and ascorbic acid derivatives.

The components included in the cosmetic composition of the present invention include components commonly used in cosmetic compositions in addition to retinoid derivatives as active ingredients and include conventional adjuvants such as antioxidants, stabilizers, solubilizers, vitamins, Carrier.

The composition of the present invention can be prepared in any formulations conventionally produced in the art, and can be used in various forms such as softening agents, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, A cleansing foam, a cleansing water, a pack, a gel, a powder, a body lotion, a body cream, a body oil, a body essence and the like.

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

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.

Hereinafter, preferred embodiments of the present invention will be described. The following examples are provided for the purpose of more clearly illustrating the present invention and are not intended to limit the scope of the present invention.

[Example]

Example  1: 1,5- Bis Retinamido  2- methyl Pentane  synthesis

Retinoic phosphoric acid 35 g (0.0116 mol) was added dropwise here, the _{(PCl 3) 16.3 g (0.0116} mol) phosphorus trichloride to the was dissolved in dry toluene 150 ㎖ and stirred for 15 hours under while being shielded from light and moisture at room temperature, nitrogen . The resulting retinoic acid chloride solution was added dropwise to a solution of 6.77 g (0.058 mol) of 2-methyl-1,5-diaminopentane and 11.8 g (0.117 mol) of triethylamine in 100 ml of anhydrous dichloromethane under ice cooling for 30 minutes And then stirred at room temperature for 5 hours. The reaction solution was added to 250 ml of a saturated aqueous sodium chloride solution, and the organic layer was separated, washed with water, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was separated by column chromatography (SiO ₂ , 200-400 mesh, ethylacetate / hexane = 1: 3, v / v) to give 56.1 g (yield: 71%) of the title compound.

Experimental Example  1: B16 Melanoma  Production of melanin using cell lines Inhibition  Confirm

Rodent melanoma cell line, B16 cell line (ATCC CRL-6323) with 10% fetal calf cultured in serum with 100 U / ㎖ penicillin, 100 ㎍ / ㎖ streptomycin is added to the supplemented DMEM medium by 37 ℃, 5% CO _2, conditions Respectively.

B16 cells cultured as described above were inoculated into a well plate at 1 × 10 ⁵ per well using medium DMEM (Invitrogen-Gibco-BRL, Grand Island, NY) and melanocyte stimulating hormone (α-MSH) 2 ml of a sample solution containing 100 nM of 1,5-bis-retinamido 2-methylpentane at 0 / / ml, 1 쨉 g / ml, 5 쨉 g / ml, 10 쨉 g / ml and 20 쨉 g / . Next, after 72 hours of treatment, the medium was washed with phosphorylation buffer solution, and 100 μl of melanin extract solution (1N NaOH + 50% DMSO) was added at a rate of 80 ° C to dissolve the cells at 80 ° C. Was measured. The results are shown in Fig.

1 is a graph showing the amount of melanin produced according to the concentration of 1,5-bis-retinamido 2-methylpentane treatment according to an embodiment of the present invention.

1, in all groups treated with 1-g / ml, 5 μg / ml, 10 μg / ml and 20 μg / ml of 1,5-bis- retinamido 2-methylpentane with α- , 5-bis-retinamido showed a remarkable inhibitory effect on melanin formation as compared with the group not treated with 2-methylpentane. In addition, from 1 μg / ml of 1,5-bis-retinamido 2-methylpentane, the content of melanin in the cells decreased significantly compared to the untreated group. Based on these results, Production was suppressed.

Experimental Example  2: Tyrosinase Low performance  Confirm

220 μl of 0.1 M phosphate buffer (pH 6.5), 20 μl of tyrosinase extracted from B16 cells, and 20 μl of mushroom tyrosinase were placed in the test tube in this order. 40 μl of 1.5 mM tyrosine solution was added to this solution, and reacted at 37 ° C for 10 to 15 minutes. The absorbance was measured at 490 nm using a microplate reader. Each sample solution of Test Example 1 was treated with 200 mu l of the solution before treatment with tyrosine, and 0.1 M phosphate buffer (pH 6.5) was added as a blank solution instead of the sample solution. The results are shown in Fig.

2 is a graph showing tyrosinase activity according to 1,5-bis-retinamido 2-methylpentane treatment concentration according to an embodiment of the present invention.

As shown in FIG. 2, the group treated with 1-g / ml, 5 μg / ml, 10 μg / ml and 20 μg / ml of 1,5-bis- retinamido 2-methylpentane with α- 5-bis-retinamido showed remarkable inhibitory effect on tyrosinase activity as compared with the group not treated with 2-methylpentane.

Experimental Example  3: allergy  exam

The allergy test of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention was confirmed by a safety test using ethanol as a carrier medium [Reference: J. Appl. Toxicol., 1990, 10 (3), 173-180). Retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide and 1,5-bis-retinamido 2-methylpentane as control substances were dissolved in acetone / olive oil (4/1, v / v) solution. Auricular lymph nodes were isolated from rats after 3 days of 30 μl of rats (Balb / c) on both ears. The lymph nodes were pulverized into single cells, and radioactive isotopes ( ³ H-thymidine) were added to the cells for 24 hours. Cellular amplification (CPM) was measured and the results are shown in Table 1 below.

In Table 1, retinoyl palmitate and retinoic acid as control substances showed higher allergy induction than 5 times, while 1,5-bis-retinamido 2-methylpentane showed 1.2 and 1.6 times in 0.3% and 1% solutions, respectively Than that of ethyl retinoate and PEG-retinamide, which were three times less inducible than ethanol.

sample Lymph node cell
(10 < ⁷ > cells / ml) Cpm (average) Amplification degree ethanol 1.13 1892 Medium Retinyl palmitate
(0.3%) 3.62 10119 5.35 Retinyl palmitate
(One%) 4.29 12332 6.52 Retinoic acid
(0.3%) 4.56 13224 6.99 Retinoic acid
(One%) 4.98 14612 7.72 Ethyl retinoate
(0.3%) 1.93 4535 2.40 Ethyl retinoate
(One%) 2.34 5890 3.11 PEG-retinamide
(0.3%) 1.64 3577 1.89 PEG-retinamide
(One%) 1.87 4337 2.29 1,5-Bis Retinamido 2-Methylpentane
(0.3%) 1.24 2256 1.19 1,5-Bis Retinamido 2-Methylpentane
(One%) 1.47 3015 1.59

Experimental Example  4: Skin irritation test

In order to confirm the skin irritation degree of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention, a patch test was conducted using Guinea Pig (Reference: Assoc. Food and Drug officials US, 1959, 46-59; Method of testing primary irritant substances, 1973, 38 (187), 1500-1541].

A 0.3% concentration of sample solution was prepared by transferring O / W emulsions of water and propylene glycol. The hair of the area (s) to be applied was removed and adapted to the surrounding environment for precise measurement for 24 hours. The coated area (1.5 cm x 1.5 cm) was treated with a gauze soaked with a specimen and sealed with a solid material sheet to prevent evaporation and loss of the specimen, and fixed with a resilient bandage for 48 hours. The degree of irritation was determined 24 hours after the closed pellet was removed (72 hours after the patch), and the results are shown in Table 2 below.

sample Stimulation index Irritation degree O / W formulation 1.0 Weak stimulation O / W + retinyl palmitate (0.3%) 1.0 Weak stimulation O / W + retinoic acid (0.3%) 1.5 Irritation of severity O / W + ethyl retinoate (0.3%) 1.0 Weak stimulation O / W + PEG-retinamide (0.3%) 0.7 Micro stimulation O / W + 1,5-bis Retinamido 2-Methylpentane (0.3%) 0.6 Micro stimulation

As shown in Table 2 above, 1,5-bisretinamido 2-methylpentane showed significantly less irritation than retinyl palmitate and retinoic acid.

Experimental Example  5: Cytotoxicity test

In order to verify the primary safety of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention as an active ingredient for medicines or cosmetics, a continuous cell line of Chinese Hamster lung fibroblasts (V79 -4) was cultured and the cytotoxicity was confirmed by an MTT experiment (Reference: Journal of Immunological Methods, 1983, 65, 55 ~ 63), and the results are shown in FIG.

3, 1,5-bis Retinamido 2-methyl pentane showed no toxicity at a test concentration similar to that of ethyl retinoate used as a control. However, retinyl palmitate and retinoic acid were toxic at> 10 μM, and PEG-retinamide showed rapid toxicity at high concentrations (> 25 μM).

Experimental Example  6: Light stability  exam

In order to examine the light stability of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention, Spectroline Model CM-10 (Fluorescence analysis cabinet; UV-A light (wavelength: 356 nm) was irradiated with time using Spectronics Corporation, Westbury, New York, USA and then qualitatively confirmed by NMR.

In Table 3, 1,5-bis-retinamido 2-methylpentane appears photostable as compared to conventional retinoid derivatives and exhibits similar stability compared to PEG-retinamide.

Experimental Example  7: Thermal stability  exam

To examine the thermal stability of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention, a constant temperature and humidity chamber (at a humidity of 56%) at room temperature, 0 ° C, 37 ° C and 50 ° C, , And the results are shown in Table 4 below. ≪ tb > < TABLE >

As shown in Table 4, 1,5-bis-retinamido 2-methylpentane showed excellent thermal stability at 37 ° C and 50 ° C.

Experimental Example  8: Percutaneous absorption  exam

Retinol, retinyl palmitate, retinoic acid, ethyl retinoate and PEG-retinamide were used as a control substance for the percutaneous absorption test of 1,5-bis-retinamido 2-methylpentane prepared in Example 1 according to the present invention , And a 1: 1 mixed solvent of oil (caprylic capric triglyceride) and ethanol was used as a medium (Reference: J. Invest Dermatol., 1998, 91; 56-61].

First, the skin (back region) of a 7-week-old female hairless mouse was cut and 150 μl of 50 mM sample solution was applied to the skin of 1.7 cm ² . After 24 hours, the receptor solution, which is a 50 mM PBS buffer (pH 7.4) containing 2% Volpo 20 ^™ (Oleth-20), and the substance absorbed into the skin were extracted using a transdermal absorption detector (Frnaz cell) Chromatography (HPLC) quantitative analysis showed the results in Table 5 below.

Referring to Table 5, it was confirmed that 1,5-bis-retinamido 2-methylpentane can be percutaneously absorbed at three times of retinol, 5.4 times of retinyl palmitate, and 2.4 times of retinoic acid, It was confirmed that it exhibited almost the same percutaneous absorption rate as that of PEG-retinamide known to be known.

Experimental Example  9: Hydrolysis test in rat serum

The rate of hydrolysis of ethyl retinoate in the form of an ester in the rat serum and PEG-retinamide in the amide form and the 1,5-bis-retinamido 2-methyl pentane prepared in Example 1 according to the present invention, (37 < 0 > C).

80 mg of the sample was dissolved in 5 ml of rat serum each, and the resulting solution was incubated at 37 ° C. At time intervals, 0.7 ml of the serum mixture was taken and extracted twice with 2 ml of dichloromethane. The dichloromethane extract was dried over Na ₂ SO ₄ , filtered and evaporated to dryness under reduced pressure. Water was added to the dry residue and filtered. The filtrate was analyzed by reverse phase HPLC (Betasil C18, 100 x 2) analysis and the results are shown in Fig.

Half-life (t ^1/2) of hydrolysis of from 4 was confirmed to be 32 hours for the amide form of the ethyl ester was 8.7 hours for the form, 1,5-bis retinoic amido-2-methyl pentane. On the other hand, it was confirmed that the amide form of PEG-retinamide maintained about 60% even after 48 hours or more.

Hereinafter, the formulations of the present invention are exemplified as a soft lotion, a convergent lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence and a pack, but the formulation of the cosmetic composition of the present invention is not limited thereto.

Formulation Example  1: Softening longevity ( skin )

The number of softening times containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 6 below.

ingredient Content (% by weight) Retinoid derivative One glycerin 5 1,3-butylene glycol 3 Betaine One Allantoin 0.1 DL-Panthenol 0.3 EDTA-2Na 0.02 Sodium hyaruronate powder 0.05 ethanol 5 Octyldodec-16 0.2 Polyoxyethylene hardened castor oil 0.2 incense Suitable amount antiseptic Suitable amount Pigment Suitable amount Purified water Balance Sum 100

Formulation Example  2: Nourishing lotion (lotion)

A nutritional lotion containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 7 below.

ingredient Content (% by weight) Retinoid derivative 3 Glyceryl stearate SE 1.5 Cetearyl alcohol 1.0 Sheer butter 1.5 Polysorbate 60 1.3 Sorbitan stearate 0.5 Hardened vegetable oil One Mineral oil 5 Squalane 3 Cyclomethicone 2 Dimethicone 0.8 Tocopheryl acetate 0.5 Carbomer 0.12 glycerin 5 1,3-butylene glycol 3 Sodium hyaruronate powder 0.05 Triethanolamine 0.12 incense Suitable amount antiseptic Suitable amount Pigment Suitable amount Distilled water Balance Sum 100

Formulation Example  3: Nourishing cream

A nutritional cream containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 8 below.

ingredient Content (% by weight) Retinoid derivative 3 Pro-type glycerin monostearate 2 Cetearyl alcohol 2 Stearic acid 1.5 Polysorbate 60 1.5 Sorbitan stearate 0.6 Hydrogenated polyisobutene One Squalane 3 Mineral oil 5 Cyclomethicone 5 Dimethicone One Tocopheryl acetate 0.5 glycerin 5 Betaine 3 Triethanolamine One Xanthan gum 0.05 incense Suitable amount antiseptic Suitable amount Pigment Suitable amount Distilled water Balance Sum 100

Formulation Example  4 : Massage  cream

A massage cream containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 9 below.

ingredient Content (% by weight) Retinoid derivative 3 Pro-type glycerin monostearate 1.5 Cetearyl alcohol 1.5 Stearic acid One Polysorbate 60 1.5 Sorbitan stearate 0.6 Isostearyl isoserate 5 Squalane 5 Mineral oil 35 Dimethicone 0.5 Hydroxyethylcellulose 0.12 glycerin 6 1,3-butylene glycol 3 Triethanolamine 0.3 incense Suitable amount antiseptic Suitable amount Pigment Suitable amount Distilled water Balance Sum 100

Formulation Example  5: essence

Essences containing retinoid derivatives of Example 1 were prepared according to the conventional method as shown in Table 10 below.

ingredient Content (% by weight) Seaweed extract 3 glycerin 6 Betaine 5 PEG 1500 2 Allantoin 0.1 DL-Panthenol 0.3 EDTA-2Na 0.02 Hydrogenated lecithin 0.6 Hydroxyethylcellulose 0.1 Sodium hyaruronate powder 0.08 Carboxyvinyl polymer 0.2 Triethanolamine 0.2 Ceramide 0.2 Octyldodecanol 3 Squalane 3 Polysorbate 60 0.4 Glyceryl stearate SE 1.5 incense Suitable amount antiseptic Suitable amount Pigment Suitable amount Distilled water Balance Sum 100

Formulation Example  6: Pack

A pack containing the retinoid derivative of Example 1 was prepared according to a conventional method as shown in Table 11 below.

ingredient Content (% by weight) Retinoid derivative One Polyvinyl alcohol 15 Cellulose sword 0.15 glycerin 3 PEG 1500 2 Betaine 2 DL-Panthenol 0.4 Allantoin 0.1 Triethanolamine 0.2 Nicotinamide 0.5 ethanol 6 PEG 40 hardened castor oil 0.3 incense Suitable amount antiseptic Suitable amount Pigment Suitable amount Distilled water Balance Sum 100

Claims (4)

A cosmetic composition for skin whitening comprising a retinoid derivative represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

(Wherein,
R ₁ and R ₂ are the same or different and each is hydrogen or a straight or branched alkyl group having 1 to 6 carbon atoms. The method according to claim 1,
Wherein R ₁ is a methyl group and R ₂ is Wherein the composition is hydrogen. The method according to claim 1,
Wherein the content of the retinoid derivative is 0.001 to 10% by weight based on the total weight of the total cosmetic composition. The method according to claim 1,
The cosmetic composition for skin whitening may be selected from the group consisting of softening longevity, astringent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, gel, powder, body lotion, , A body oil, and a body essence. The cosmetic composition for skin whitening according to claim 1,

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