KR102296103B1 - New cyclic skin whiteninig agent - Google Patents

Abstract

상기 식에서

는 방향족 고리화합물로부터 유래되고, B는 수소, 옥소(oxo, =O), 아미노(amino, -NH₂), 이미노(imino, =NH), C₁ 내지 C₁₀의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬기, 알콕시, 모노알킬아미노기, 또는 디알킬아미노기이고,
C_n, C_n+1 및 C_n+2는 상기 고리화합물에 존재하는 이웃하는 3개의 탄소로서 n은 양의 정수이다.
R₁ 은 수소, 히드록시, 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬기 또는 알콕시기이고,
X 및 Y는 수소, 히드록시, 포화 혹은 불포화된 직쇄 또는 분지쇄의 알콕시 또는 아실옥시에서 선택되어지며, X 및 Y 둘 중 하나는 수소이다.
R₂, R_3, R₄ 및 R₅는 각각 독립적으로 수소, 알킬, 알콕시, 아실옥시, 아실옥시메틸, 옥소, 히드록시, 비닐, 니트릴, 카르복알데히드, 카보니트릴, 및 알데히드로부터 선택된 하나이상의 치환기이다.
The present invention provides a cyclic derivative compound having a chemical structure of the following general formula (I), or a pharmacologically acceptable salt thereof, having excellent whitening effect:

in the above formula

is derived from an aromatic ring compound, and B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or a branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,
C _n , C _n+1 and C _n+2 are three adjacent carbons present in the cyclic compound, and n is a positive integer.
R ₁ is hydrogen, hydroxy, saturated or unsaturated straight-chain or branched alkyl group or alkoxy group,
X and Y are selected from hydrogen, hydroxy, saturated or unsaturated straight or branched chain alkoxy or acyloxy, and one of X and Y is hydrogen.
R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

Description

Skin whitening agent containing novel cyclic compound {New cyclic skin whiteninig agent}

The present invention relates to a novel skin whitening agent, and more particularly, to an external skin preparation, specifically, to a composition for external application for skin excellent in whitening effect.

Skin blackening (melanogenesis) is a defense mechanism in melanocytes against stimuli such as ultraviolet rays, and melanin-producing activity is increased. It is the result. Although melanin has a protective effect on the skin, hyperpigmentation of the skin causes melasma, freckles, darkening of the skin after skin inflammation, and age-related pigment spots. may even cause In the process of melanin production, an enzyme called tyrosinase acts on tyrosine, a kind of amino acid, to convert it into DOPA and dopaquinone, and then it is made through a non-enzymatic oxidation reaction, which is abnormal deposition in the skin. This is known to cause spots and age spots. Substances that inhibit melanin production, such as hydroquinone, arbutin, vitamin C and derivatives thereof, have been developed for alleviating, preventing, and treating such pigmentation, blemishes, and spots, and whitening cosmetics containing them have been disclosed. and Korean Patent Publication No. 2005-0509848 discloses a whitening cosmetic containing a keractone derivative isolated from the previous issue. In addition, Korean Patent Publication No. 2005-0479741 discloses a whitening cosmetic containing a glucose acylated derivative. Among these, hydroquinone has been recognized for its effectiveness, but its use is generally limited because of its sensitization. Ascorbic acid is easily oxidized, and cosmetics containing it cause discoloration and odor problems. Substances derived from plant extracts have significant differences in efficacy depending on the plant's origin, making it difficult to maintain the homogeneity of the product, and glucose acylated derivatives There is a disadvantage that the synthesis efficiency is very low.

Accordingly, the present inventors synthesized a derivative of a novel cyclic compound of the present invention while continuing research to develop a material that has high synthesis efficiency and inhibits melanin production, and confirmed their excellent whitening effect, the present invention completed.

An object of the present invention is to provide a composition for skin whitening that is easy to synthesize, has no side effects on the skin, and has an excellent melanin production inhibitory effect and thus has an excellent skin pigmentation inhibitory effect.

The above object is achieved by a cyclic derivative compound having the chemical structure of the general formula (I) or a pharmacologically acceptable salt thereof.

는 방향족 고리화합물로부터 유래되고, B는 수소, 옥소(oxo, =O), 아미노(amino, -NH₂), 이미노(imino, =NH), C₁ 내지 C₁₀의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬기, 알콕시, 모노알킬아미노기, 또는 디알킬아미노기이고, in the above formula

is derived from an aromatic ring compound, and B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or a branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,

C _n , C _n+1 and C _n+2 are three adjacent carbons present in the cyclic compound, and n is a positive integer.

R ₁ is hydrogen, hydroxy, saturated or unsaturated straight-chain or branched alkyl group or alkoxy group,

X and Y are selected from hydrogen, hydroxy (-OH), saturated or unsaturated straight or branched chain alkoxy or acyloxy, and either X or Y is hydrogen.

R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

Since the compound according to the present invention is easy to synthesize and has no side effects on the skin, as well as exhibits a melanin production inhibitory effect and a pigmentation inhibitory effect, a composition containing the same can be used as a composition for skin whitening.

The present invention provides a compound having a chemical structure of the following general formula (I), or a pharmacologically acceptable salt thereof, having excellent whitening effect:

는 방향족 고리화합물로부터 유래되고, B는 수소, 옥소(oxo, =O), 아미노(amino, -NH₂), 이미노(imino, =NH), C₁ 내지 C₁₀의 포화 혹은 불포화된 직쇄 또는 분지쇄의 알킬기, 알콕시, 모노알킬아미노기, 또는 디알킬아미노기이고, in the above formula

is derived from an aromatic ring compound, and B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or a branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,

C _n , C _n+1 and C _n+2 are three adjacent carbons present in the cyclic compound, and n is a positive integer.

R ₁ is hydrogen, hydroxy, saturated or unsaturated straight-chain or branched alkyl group or alkoxy group,

X and Y are selected from hydrogen, hydroxy (-OH), saturated or unsaturated straight or branched chain alkoxy or acyloxy, and either X or Y is hydrogen.

R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

In the above, the cyclic compound is an aromatic compound, and may have a structure in which 1 to 4 or more rings are bonded, and may be a homo or heterocyclic compound. The heterocyclic compound preferably contains oxygen or nitrogen in the ring structure, or may contain both oxygen and nitrogen.

화합물로는 특별히 한정되지는 않으나, 예를 들어 벤젠, 피리딘, 피리다진, 피리미딘, 인덴, 인단, 벤조퓨란, 벤조티오펜, 인돌, 벤지미다졸, 벤조티아졸, 퓨린, 나프탈렌, 퀴놀린, 이소퀴놀린, 쿠마린, 시네올린, 퀴녹살린, 플라본, 플라반, 바이벤질, 1,3-디페닐-프로판, 1,3-디페닐-2-프로펜 등을 들 수 있다.of the general formula (I)

The compound is not particularly limited, but for example, benzene, pyridine, pyridazine, pyrimidine, indene, indane, benzofuran, benzothiophene, indole, benzimidazole, benzothiazole, purine, naphthalene, quinoline, iso quinoline, coumarin, cineolin, quinoxaline, flavone, flavan, bibenzyl, 1,3-diphenyl-propane, 1,3-diphenyl-2-propene, and the like.

는 적어도 1개 이상의 히드록시기가 각각 결합된 고리화합물로부터 유래되어질 수 있으며, 바람직하게는 5원환 또는 6원환이 1개 또는 2개가 결합된 고리화합물로 구조 내에 적어도 1개 이상, 바람직하게는 1개 ~ 6개의 인접하는 탄소에 히드록시기가 결합된 화합물로부터 유래될 수 있다. Also, in the above general formula (1),

may be derived from a cyclic compound to which at least one or more hydroxyl groups are each bonded, preferably a cyclic compound in which one or two 5-membered or 6-membered rings are bonded, and at least one or more, preferably 1 ~ It may be derived from a compound in which a hydroxyl group is bonded to six adjacent carbons.

In the general formula (1), B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C _{1 To} C ₁₀ saturated or unsaturated straight chain or branched a chain alkyl group, alkoxy, monoalkylamino group, or dialkylamino group.

In the general formula (1), R ₁ is hydrogen, hydroxy, saturated or unsaturated straight-chain or branched alkyl or alkoxy, preferably C ₁ to C ₁₀ saturated or unsaturated straight-chain or branched alkyl or alkoxy, and more preferably _{, when R 1} is alkyl, C ₁ to C ₁₀ , more preferably C ₄ to C ₈ saturated or unsaturated straight-chain or branched alkyl, and when R ₁ is alkoxy, C ₁ to C ₁₂ , more preferably C ₂ to C ₁₀ is saturated or unsaturated straight-chain or branched alkoxy.

X and Y are selected from hydrogen, hydroxy (-OH), saturated or unsaturated straight-chain or branched alkoxy or acyloxy, preferably, when X and Y are alkoxy, C ₂ to C ₁₀ , more preferably C ₄ to C ₈ saturated or unsaturated straight-chain or branched alkoxy, and when X and Y are acyloxy, C ₁ to C ₁₂ , more preferably C ₂ to It is C ₁₀ saturated or unsaturated straight-chain or branched acyloxy. One of X and Y is hydrogen.

R _{2 ,} R ₃ , R ₄ and R ₅ may each be the same or different, and each of hydrogen, hydroxy, vinyl, oxo and alkyl having 1 to 30 carbon atoms, alkoxy, acyloxy, acyloxymethyl, nitrile, carboxyl It may be selected from the group of double aldehydes, carbonitrile and aldehydes, but is not necessarily limited thereto.

가 벤젠으로부터 유래된다면 n은 최대 4의 값을 가질 수 있다.
C _n , C _n+1 and C _n+2 are three adjacent carbons present in the cyclic compound, n has a positive number and may be determined within the range of the total number of atoms constituting the ring. For example, said

n can have a maximum value of 4 if is derived from benzene.

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

The compound of the present invention is an aromatic ring compound, preferably a homo or heterocyclic compound in which one or two 5-membered or 6-membered rings are bonded, as shown in the following scheme, wherein a hydroxyl group is bonded to at least one carbon in the structure. After dissolving the compound in a suitable organic solvent, one or two or more types of acyl halide or alkyl halide are mixed and slowly added dropwise at an appropriate equivalent ratio to obtain through an ester reaction or an ether reaction with the hydroxyl group in the cyclic structure, or , can be obtained by subjecting this reactant to hydrogenation again. In this case, the organic solvent that can be used for the reaction is not particularly limited, and examples thereof include dichloromethane, chloroform, tetrahydrofuran, acetonitrile, dimethylformamide, pyridine, and dimethylformamide. In particular, sodium hydride (NaH) or potassium carbonate (K ₂ CO ₃ ) may be used as a reaction catalyst.

[Scheme 1]

In Scheme 1, R ₆ is a C _1-12 saturated or unsaturated alkyl, and both linear or branched chain types are possible.

R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

[Scheme 2]

In Reaction Scheme 2, R ₆ is a C _1-12 saturated or unsaturated alkyl, which may be linear or branched.

R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

[Scheme 3]

In Scheme 3, R ₈ is hydrogen and C _1-12 saturated or unsaturated alkyl, which may be straight-chain or branched, and R ₇ is C _1-12 saturated or unsaturated alkyl or acyl, which is straight-chain or branched. All is possible.

B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C ₁ to C ₁₀ A saturated or unsaturated straight-chain or branched alkyl group, alkoxy, mono an alkylamino group or a dialkylamino group.

R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

[Scheme 4]

In Scheme 4, R ₈ is hydrogen and C _1-12 saturated or unsaturated alkyl, which may be straight-chain or branched, and R ₇ is C _1-12 saturated or unsaturated alkyl or acyl, which is straight-chain or branched. All is possible.

B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C ₁ to C ₁₀ A saturated or unsaturated straight-chain or branched alkyl group, alkoxy, mono an alkylamino group or a dialkylamino group.

R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.

가 벤젠이고, R_2, R_3, R₄ 및 R₅ 가 수소인 경우 제조되어지는 물질명을 예시하면 하기와 같다.As a more specific example of the compound of general formula (I) according to the present invention, a compound having a ring structure among materials prepared according to Scheme 1

When is benzene and R _{2 ,} R _{3 ,} R ₄ and R ₅ are hydrogen, the name of the material to be prepared is as follows.

For example, 2-methoxy benzoic acid methyl ester, 2-ethoxy benzoic acid ethyl ester, 2-propoxy benzoic acid propyl ester, 2-butoxy benzoic acid butyl ester, 2-pentyloxy benzoic acid pentyl ester, 2-hexyloxy benzoic acid hexyl ester, 2-octyloxy benzoic acid octyl ester, 2-decyloxy benzoic acid decyl ester, and the like.

In addition, among the materials prepared through Scheme 1, when R _{2 ,} R _{3 ,} R ₄ and R ₅ are hydrogen and R6 is pentyl, the names of the materials prepared are as follows.

For example, 2-pentyloxy-benzoic acid pentyl ester, 3-pentyloxy-benzoic acid pentyl ester, 1-pentyloxy-2-naphthoic acid pentyl ester, 3-pentyloxy-2-naphthoic acid pentyl ester. ester, 3-pentyloxy-4-pyridinecarboxylic acid pentyl ester, 3-pentyloxy-4-quinoline carboxylic acid pentyl ester, and the like, but is not limited thereto.

가 벤젠이고, B가 옥소 이고, R_2, R_3, R₄ 및 R₅이 수소이며 R8이 메틸 일 때 제조되어지는 물질명을 예시하면 하기와 같다.In addition, among the materials prepared through Scheme 3,

When is benzene, B is oxo, R _{2 ,} R _{3 ,} R ₄ and R ₅ are hydrogen, and R8 is methyl, the name of the material prepared is as follows.

For example, 1-(2-methyloxy-phenyl)-ethanone, 1-(2-pentyloxy-phenyl)-ethanone, 1-(2-hexyloxy-phenyl)-ethanone, acetic acid 2-acetyl-phenyl ester, 2-ethylhexanoic acid 2-acetyl-phenyl ester, and octanoic acid 2-acetyl-phenyl ester, and the like, but are not limited thereto.

The present invention also provides a pharmaceutical composition for external use on the skin for the prevention, treatment and whitening of hyperpigmentation, melasma, freckles and age spots, comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient. .

The compounds of the present invention represented by the general formula (I) can be prepared as pharmaceutically acceptable salts and solvates according to conventional methods in the art.

As the salt, an acid addition salt formed with a pharmaceutically acceptable free acid is useful. Acid addition salts are prepared by conventional methods, for example, by dissolving the compound in an aqueous solution of excess acid and precipitating the salt with a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equal molar amounts of compound and acid or alcohol (eg glycol monomethyl ether) in water may be heated to dryness followed by evaporation of the mixture, or the precipitated salt may be filtered off with suction.

At this time, organic acids and inorganic acids can be used as free acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, etc. can be used as inorganic acids, and methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid, Citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid ( gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid and the like can be used.

In addition, bases can be used to prepare pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. In this case, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as the metal salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

The pharmaceutically acceptable salts of formula (I) above include salts of acidic or basic groups that may be present in compounds of formula (I), unless otherwise indicated. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of a hydroxyl group, and other pharmaceutically acceptable salts of an amino group include hydrobromide, sulfate, hydrogen sulfate, phosphate, hydrogen phosphate, dihydrogen. There are salts of phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p -toluenesulfonate (tosylate), and methods or processes for preparing salts known in the art can be manufactured through

The composition comprising the compound of the present invention may further contain a suitable carrier, excipient or diluent according to a conventional method.

Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition comprising the compound of the present invention is formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, or sterile injection solutions, respectively, according to a conventional method. can be used for

Specifically, in the case of formulation, it can be prepared using a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, and a surfactant usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract, for example, starch, calcium carbonate, sucrose ), lactose, gelatin, etc. can be mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral use include suspensions, solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives are included. can Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

The composition for prevention, treatment and whitening of hyperpigmentation, melasma, freckles and age spots comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient is an external preparation for skin that can be applied to the skin As a formulation, it can be prepared and used as a pharmaceutical composition in the form of a skin external preparation of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta, or cataplasma, but is not limited thereto.

The preferred dosage of the compound of formula (I) of the present invention or a pharmacologically acceptable salt thereof varies depending on the patient's condition and weight, the degree of disease, drug form, administration route and duration, but may be appropriately selected by those skilled in the art. can However, for a desirable effect, the compound of the present invention is preferably administered at 0.0001 to 100 mg/kg per day, preferably 0.001 to 10 mg/kg. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way.

The compounding amount of the compounds according to the present invention in the pharmaceutical composition for external use is preferably 0.0001 to 20% by weight, more preferably 0.001 to 10% by weight, based on the total weight of the composition, which is less than 0.001% by weight, the whitening effect is reduced This is because it is difficult to expect an increase in the effect even if it is blended if it exceeds 20% by weight.

In addition, the pharmaceutical dosage forms of the compounds of the present invention may be used in the form of pharmaceutically acceptable salts thereof, and may be used alone or in combination with other pharmaceutically active compounds as well as in an appropriate group.

The present invention provides a cosmetic composition for the prevention, improvement and whitening of hyperpigmentation, freckles, freckles and age spots comprising the compound of Formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

The composition comprising the compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient can be used in various ways, such as cosmetics and face washes for skin wrinkle improvement effect. Products to which the present composition can be added include, for example, cosmetics such as various creams, lotions, and skins, and cleansing agents, face washes, soaps, treatments, and cosmetics.

The cosmetic of the present invention includes a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extract.

The water-soluble vitamin may be any as long as it can be formulated in cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine hydrochloride, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, etc. and their salts (thiamine hydrochloride, sodium ascorbate salt, etc.) and derivatives (ascorbic acid-2-phosphate sodium salt, ascorbic acid-2-phosphate magnesium salt, etc.) are also included in the water-soluble vitamins that can be used in the present invention. Included. Water-soluble vitamins can be obtained by conventional methods such as a microbial transformation method, a purification method from a microbial culture, an enzymatic method or a chemical synthesis method.

The oil-soluble vitamins may be any as long as they can be formulated in cosmetics, but preferably include vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol). , their derivatives (ascorbine palmitate, ascorbine stearate, ascorbine dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherol nicotinic acid, vitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantothenyl ethyl ethers, etc.) are also included in the oil-soluble vitamins used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as a microbial transformation method, a purification method from a microbial culture, an enzyme or a chemical synthesis method, and the like.

The macromolecular peptide may be any compound as long as it can be formulated in cosmetics, and preferred examples include collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, and keratin. Polymeric peptides can be purified and obtained by conventional methods such as purification from a microbial culture solution, enzyme method or chemical synthesis method, or can be purified and used from natural products such as dermis of pigs or cattle, silk fibers of silkworms, etc.

The high molecular weight polysaccharide may be any compound as long as it can be formulated in cosmetics, but preferably hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate, or a salt thereof (such as sodium salt). For example, chondroitin sulfate or a salt thereof can be used after purification from mammals or fish.

The sphingolipids may be any as long as they can be formulated in cosmetics, and ceramides, phytosphingosine, sphingoglycolipids and the like are preferred. The sphingolipid can be purified by a conventional method from mammals, fish, shellfish, yeast or plants, or can be obtained by chemical synthesis.

The seaweed extract may be any type as long as it can be formulated in cosmetics, but preferably brown algae extract, red algae extract, green algae extract, etc., and calrageenan purified from these seaweed extracts, arginic acid, sodium alginate, Potassium alginate and the like are also included in the seaweed extract used in the present invention. The seaweed extract can be obtained by purification from seaweed by a conventional method.

In the cosmetic of the present invention, in addition to the above essential ingredients, if necessary, other ingredients usually blended in cosmetics may be blended.

Other ingredients that may be added include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, A blood circulation promoter, a cooling agent, a restrictive agent, purified water, etc. are mentioned.

Examples of the fat and oil component include ester fats and oils, hydrocarbon oils and fats, silicone oils and fats, fluorine oils and fats, animal oils and fats, and vegetable oils and fats.

Examples of ester-based oils and fats include glyceryl tri-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, stearic acid. Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoalkyl neopentanoate, tri (caprylic acid, capric acid) glyceryl, trimethylol propane tri-2-ethylhexanoate, trimethylol propane triisostearate, pentaelysitol tetra2-ethylhexanoate , cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostea laurate Reel, isotridecyl myristate, isocetyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isostearate isopropyl, 2-ethylhexanoate cetoster Aryl, 2-ethyl stearyl hexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicapric acid, di(caprylic acid, capric acid) propylene glycol, dicaprylic acid propylene glycol, dicaprylate Neopentyl glycol phosphate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate , octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerol oleate, polyglycerol isostearate, Triisocetyl citrate, triisoalkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, dimalate Isostearyl, 2-ethylhexyl hydroxystearate, di2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, Cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytsteryl isostearate, phytsteryl oleate, 12-stealoyl Ester types, such as isocetyl hydroxy stearate, 12-stealoyl hydroxy stearyl stearate, and 12-stealoyl hydroxy stearate isostearyl, etc. are mentioned.

Examples of hydrocarbon-based oils and fats include hydrocarbon-based oils and fats such as squalene, liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybudene, microcrystalline wax, petrolatum.

Examples of silicone oils and fats include polymethyl silicone, methylphenyl silicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane/methylcetyloxysiloxane copolymer, dimethylsiloxane/methylstealloxysiloxane copolymer, and alkyl Modified silicone oil, amino modified silicone oil, etc. are mentioned.

Perfluoropolyether etc. are mentioned as fluorine-type fats and oils.

Animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, saffron oil, soybean oil, corn oil, rapeseed oil, passerine oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil , cottonseed oil, palm oil, kukui nut oil, wheat germ oil, rice germ oil, shea butter, cranberry colostrum, marcadeumia nut oil, meadow home oil, egg yolk oil, tallow oil, horse oil, mink oil, orange rapie oil, jojoba oil , animal or plant oils and fats, such as candelabra wax, carnauba wax, liquid lanolin, and hydrogenated castor oil.

Examples of the moisturizing agent include a water-soluble low-molecular moisturizer, a fat-soluble molecular moisturizer, a water-soluble polymer, and a fat-soluble polymer.

As water-soluble low molecular weight moisturizers, serine, glutamine, sorbitol, mannitol, pyrrolidone-sodium carboxylate, glycerin, propylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol B (polymerization degree n = 2 or more), polypropylene Glycol (polymerization degree n=2 or more), polyglycerol B (polymerization degree n=2 or more), lactic acid, lactic acid salt, etc. are mentioned.

Cholesterol, cholesterol ester, etc. are mentioned as a fat-soluble low molecular weight humectant.

Examples of the water-soluble polymer include carboxyvinyl polymer, polyaspartate, tragacanth, xanthan gum, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, water-soluble chitin, chitosan, and dextrin. can

Examples of the fat-soluble polymer include polyvinylpyrrolidone/eicocene copolymer, polyvinylpyrrolidone/hexadecene copolymer, nitrocellulose, dextrin fatty acid ester, and high molecular weight silicone.

Examples of the emollient include long-chain acylglutamic acid cholesteryl ester, hydroxystearic acid cholesteryl, 12-hydroxystearic acid, stearic acid, rosin acid, and lanolin fatty acid cholesteryl ester.

Nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, etc. are mentioned as surfactant.

Nonionic surfactants include self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerol fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE Glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE hydrogenated castor oil, POE castor oil, POE/POP (polyoxyethylene/polyoxypropylene) copolymer, POE/POP alkyl ether, polyether-modified silicone, lauric acid alkanolamides, alkylamine oxides, hydrogenated soybean phospholipids, and the like.

Examples of the anionic surfactant include fatty acid soap, alpha-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkyl amide sulfate, alkyl phosphate, POE alkyl phosphate, and alkyl amide phosphate. , alkyloylalkyltaurine salts, N-acylamino acid salts, POE alkylether carboxylate salts, alkylsulfosuccinate salts, alkylsulfoacetate sodium, acylated hydrolyzed collagen peptide salts, perfluoroalkylphosphate esters, and the like. .

Examples of the cationic surfactant include alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, chloride Benzalkonium, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, quaternary ammonium salt of lanolin derivative, etc. are mentioned.

Examples of the amphoteric surfactant include carboxybetaine type, amidebetaine type, sulfobetaine type, hydroxysulfobetaine type, amidesulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidamine type, etc. Amphoteric surfactant etc. are mentioned.

Examples of organic and inorganic pigments include silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium-coated mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide. inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine, and complexes thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene/styrene copolymer, and organic pigments such as silk powder, cellulose, CI pigment yellow and CI pigment orange, and composite pigments of these inorganic pigments and organic pigments.

Examples of the organic powder include metal soaps such as calcium stearate; alkyl phosphate metal salts such as sodium cetylate, zinc laurylate, and calcium laurylate; acylamino acid polyvalent metal salts such as calcium N-lauroyl-beta-alanine, zinc N-lauroyl-beta-alanine, and calcium N-lauroyl glycine; amidesulfonic acid polyvalent metal salts such as calcium N-lauroyl-taurine and calcium N-palmitoyl-taurine; N such as N-epsilon-lauroyl-L-lysine, N-epsilon-palmitoylizine, N-alpha-paritoylolnithine, N-alpha-lauroylarginine, N-alpha-hydrogenated beef fatty acid acylarginine, etc. -Acyl basic amino acid; N-acyl polypeptides, such as N-lauroyl glycyl glycine; alpha-amino fatty acids such as alpha-aminocaprylic acid and alpha-aminolauric acid; Polyethylene, polypropylene, nylon, polymethyl methacrylate, polystyrene, a divinylbenzene-styrene copolymer, ethylene tetrafluoride, etc. are mentioned.

UV absorbers include para-aminobenzoic acid, ethyl para-aminobenzoate, amyl para-aminobenzoate, octyl para-aminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylate, benzyl cinnamate. , para-methoxycinnamic acid-2-ethoxyethyl, para-methoxycinnamic acid octyl, dipara-methoxycinnamic acid mono-2-ethylhexane glyceryl, para-methoxycinnamic acid isopropyl, diisopropyl diisopropyl cinnamic acid ester mixture, uro Cannic acid, ethyl urokanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenonesulfonic acid and salts thereof, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenonedisulfonate, dihydroxybenzophenone , tetrahydroxybenzophenone, 4- tert -butyl-4'-methoxydibenzoylmethane, 2,4,6-trianilino- p- (carbo-2'-ethylhexyl-1'-oxy)-1 and 3,5-triazine and 2-(2-hydroxy-5-methylphenyl)benzotriazole.

Examples of disinfectants include hinokitiol, triclosan, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, zinc phyllithione, benzalkonium chloride, photosensitizer. So, No. 301, mononitroguaial sodium, undecyrenic acid, etc. are mentioned.

Examples of the antioxidant include butylhydroxyanisole, propyl gallic acid, and ellisorbic acid.

Examples of the pH adjuster include citric acid, sodium citrate, malic acid, sodium malate, fmalic acid, sodium fumarate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, and the like.

Examples of the alcohol include higher alcohols such as cetyl alcohol.

In addition, blending components that may be added are not limited thereto, and any of the above components can be blended within a range that does not impair the object and effect of the present invention, but preferably 0.01 to 5% by weight relative to the total weight, More preferably, it is blended at 0.01-3% by weight.

The cosmetic of the present invention may take the form of a solution, an emulsion, a viscous mixture, or the like.

The ingredients included in the cosmetic composition of the present invention may include ingredients commonly used in cosmetic compositions in addition to the compounds of the general formula (I) as active ingredients, for example, stabilizers, solubilizers, vitamins, and pigments. and conventional adjuvants and carriers such as perfumes.

The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, emulsions, creams, lotions, packs, foundations, lotions, cosmetics, hair cosmetics, and the like.

Specifically, the cosmetic composition of the present invention is a skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, hand cream, foundation, essence, nourishing essence, It includes formulations of packs, soaps, cleansing foams, cleansing lotions, cleansing creams, body lotions and body cleansers.

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

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, and in particular, in the case of a spray, additional 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, solvating agent or 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 fatty esters, fatty acid esters of polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar or tracanth may be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide as carrier components Ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linolin derivative or ethoxylated glycerol fatty acid ester and the like can be used.

Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples.

However, the following Examples and Experimental Examples only illustrate the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Example 1. Preparation of 2-ethoxy benzoic acid ethyl ester

In a two-necked round flask at room temperature, 10 mmol of 2-hydroxy benzoic acid was added, and then 50 ml of dimethylformamide was added. After 24 mmol of potassium carbonate (K2CO3) was added as a catalyst, 24 mmol of bromo ethane was slowly added dropwise. After the dropwise addition, the reaction was carried out at room temperature for 6 hours. 500ml of purified water was added to the reaction product, and extraction was performed using 100ml of n-hexane. The hexane layer was dried under reduced pressure and then separated and purified using silica gel column chromatography (ethyl acetate: hexane = 1:50). 2-ethoxy benzoic acid ethyl ester was obtained and identified using fast atom bombardment mass spectrometry (hereinafter referred to as FAB-MS).

FAB mass : 195 [M+H] ⁺

Example 2. Preparation of 2-propoxy benzoic acid propyl ester

Except for using bromopropane instead of bromoethane, it was synthesized in the same manner as in Example 1 to obtain 2-propoxy benzoic acid propyl ester having the following physical properties.

FAB mass : 223 [M+H] ⁺

Example 3. Preparation of 2-butoxy benzoic acid butyl ester

Except for using bromobutane instead of bromoethane, it was synthesized in the same manner as in Example 1 to obtain 2-butoxy benzoic acid butyl ester having the following physical properties.

FAB mass : 251 [M+H] ⁺

Example 4. Preparation of 2-pentyloxy benzoic acid pentyl ester

Except for using bromo pentane instead of bromo ethane, it was synthesized in the same manner as in Example 1 to obtain 2-pentyloxy benzoic acid pentyl ester having the following physical properties.

FAB mass: 279 [M+H] ⁺

Example 5. Preparation of 2-hexyloxy benzoic acid hexyl ester

Except for using bromohexane instead of bromoethane, it was synthesized in the same manner as in Example 1 to obtain 2-hexyloxy benzoic acid hexyl ester having the following physical properties.

FAB mass : 307 [M+H] ⁺

Example 6. Preparation of 2-octyloxy benzoic acid octyl ester

Except for using bromo octane instead of bromo ethane, it was synthesized in the same manner as in Example 1 to obtain 2-octyloxy benzoic acid octyl ester having the following physical properties, and the characteristics are shown below.

FAB mass : 363 [M+H] ⁺

Example 7. Preparation of 2-decyloxy benzoic acid decyl ester

Except for using bromodecane instead of bromoethane, it was synthesized in the same manner as in Example 1 to obtain 2-decyloxy benzoic acid decyl ester having the following physical properties.

FAB mass : 419 [M+H] ⁺

Example 8. Preparation of 3-ethoxy benzoic acid ethyl ester

3-ethoxy benzoic acid ethyl ester having the following physical properties was obtained by synthesizing in the same manner as in Example 1, except that 3-hydroxy benzoic acid was used instead of 2-hydroxy benzoic acid.

FAB mass : 195 [M+H] ⁺

Example 9. Preparation of 3-propoxy benzoic acid propyl ester

3-propoxy benzoic acid propyl ester having the following physical properties was obtained by synthesizing in the same manner as in Example 2, except that 3-hydroxy benzoic acid was used instead of 2-hydroxy benzoic acid.

FAB mass : 223 [M+H] ⁺

Example 10. Preparation of 3-butoxy benzoic acid butyl ester

3-butoxy benzoic acid butyl ester having the following physical properties was obtained by synthesizing in the same manner as in Example 3, except that 3-hydroxy benzoic acid was used instead of 2-hydroxy benzoic acid.

FAB mass : 251 [M+H] ⁺

Example 11. Preparation of 3-pentyloxy benzoic acid pentyl ester

3-pentyloxy benzoic acid pentyl ester having the following physical properties was obtained by synthesizing in the same manner as in Example 4 except that 3-hydroxy benzoic acid was used instead of 2-hydroxy benzoic acid.

FAB mass: 279 [M+H] ⁺

Example 12. Preparation of 3-hexyloxy benzoic acid hexyl ester

3-hexyloxy benzoic acid hexyl ester having the following physical properties was obtained by synthesizing in the same manner as in Example 5, except that 3-hydroxy benzoic acid was used instead of 2-hydroxy benzoic acid.

FAB mass : 307 [M+H] ⁺

Example 13. Preparation of 3-octyloxy benzoic acid octyl ester

Except for using 3-hydroxybenzoic acid instead of 2-hydroxybenzoic acid, it was synthesized in the same manner as in Example 6 to obtain 3-octyloxybenzoic acid octyl ester having the following physical properties, and the following characteristics were obtained. indicated.

FAB mass : 363 [M+H] ⁺

Example 14. Preparation of 3-decyloxy benzoic acid decyl ester

3-decyloxy benzoic acid decyl ester having the following physical properties was obtained by synthesizing in the same manner as in Example 7, except that 3-hydroxy benzoic acid was used instead of 2-hydroxy benzoic acid.

FAB mass : 419 [M+H] ⁺

Example 15. Preparation of 5-acetyl-2-pentyloxy benzoic acid pentyl ester (5-acetyl-2-pentyloxy benzoic acid pentyl ester)

5-acetyl-2-pentyloxy benzoic acid pentyl having the following physical properties synthesized in the same manner as in Example 4 except that 5-acetyl-2-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid The ester was obtained.

FAB mass: 321 [M+H] ⁺

Example 16. 1-pentyloxy-2-naphthoic acid pentyl ester Preparation of (1-pentyloxy-2-naphthoic acid pentyl ester)

1-pentyloxy-2-naphthoic acid pentyl ester having the following physical properties was synthesized in the same manner as in Example 4 except that 1-hydroxy-2-naphthoic acid was used instead of 2-hydroxybenzoic acid. obtained.

FAB mass : 329 [M+H] ⁺

Example 17. 3-pentyloxy-2-naphthoic acid pentyl ester Preparation of (3-pentyloxy-2-naphthoic acid pentyl ester)

3-pentyloxy-2-naphthoic acid pentyl ester having the following physical properties was synthesized in the same manner as in Example 4 except that 3-hydroxy-2-naphthoic acid was used instead of 2-hydroxybenzoic acid obtained.

FAB mass : 329 [M+H] ⁺

Example 18. 3-pentyloxy-4-pyridinecarboxylic acid pentyl ester Preparation of (3-pentyloxy-4 -pyridinecarboxylic acid pentyl ester)

3-pentyloxy-4-pyridinecarboxylic acid pentyl having the following physical properties synthesized in the same manner as in Example 4 except that 3-hydroxy-4-pyridinecarboxylic acid was used instead of 2-hydroxybenzoic acid The ester was obtained.

FAB mass: 280 [M+H] ⁺

Example 19. 3-pentyloxy-quinoline-4-carboxylic acid pentyl ester Preparation of (3-pentyloxy-quinoline-4-carboxylic acid pentyl ester)

3-pentyloxy-quinoline-4-carboxyl having the following physical properties synthesized in the same manner as in Example 4 except that 3-hydroxy-quinoline-4-carboxylic acid was used instead of 2-hydroxybenzoic acid The acid pentyl ester was obtained.

FAB mass : 330 [M+H] ⁺

Example 20. Preparation of 1- (2-pentyloxy-phenyl) -ethanone (1- (2-pentyloxy-phenyl) -ethanone)

1-(2-pentyloxy-phenyl) having the following physical properties synthesized in the same manner as in Example 4 except that 1-(2-hydroxy-phenyl)-ethanone was used instead of 2-hydroxybenzoic acid -Ethanone was obtained.

FAB mass : 207 [M+H] ⁺

Example 21. Preparation of 1-(3-pentyloxy-phenyl)-ethanone (1-(3-pentyloxy-phenyl)-ethanone)

1-(3-pentyloxy-phenyl) having the following physical properties synthesized in the same manner as in Example 4 except that 1-(3-hydroxy-phenyl)-ethanone was used instead of 2-hydroxybenzoic acid -Ethanone was obtained.

FAB mass : 207 [M+H] ⁺

Example 22. Preparation of 1-(3-pentyloxy-naphthalen-2-yl)-ethanone (1-(3-pentyloxy-naphthalen-2-yl)-ethanone)

1-(3-pentyl) having the following physical properties synthesized in the same manner as in Example 4 except that 1-(3-hydroxy-naphthalen-2-yl)-ethanone was used instead of 2-hydroxybenzoic acid Oxy-naphthalen-2-yl)-ethanone was obtained.

FAB mass : 257 [M+H] ⁺

Example 23. Preparation of acetic acid 2-acetyl-phenyl ester

In a 2-neck round flask at room temperature, 10 mmol of 1-(2-hydroxy-phenyl)-ethanone was added, and then 50 ml of chloroform was added. After 12 mmol of triethylamine was added as a catalyst, 12 mmol of acetyl chloride was slowly added dropwise. After the dropwise addition, the reaction was carried out at room temperature for 2 hours. 500 ml of purified water was added to the reaction mixture, and liquid-liquid fractionation was performed. The chloroform layer was dried under reduced pressure and then separated and purified using silica gel column chromatography (ethyl acetate: hexane = 1:30). Acetic acid 2-acetyl-phenyl ester was obtained and identified using fast atom bombardment mass spectrometry (hereinafter, FAB-MS).

FAB mass: 179 [M+H] ⁺

Example 24. Preparation of 2-ethylhexanoic acid 2-acetyl-phenyl ester (2-ethylhexanoic acid 2-acetyl-phenyl ester)

2-ethylhesanoic acid 2-acetyl-phenyl ester having the following physical properties synthesized in the same manner as in Example 23 except that 2-ethylhexanoyl chloride was used instead of acetyl chloride was obtained.

FAB mass : 263 [M+H] ⁺

Example 25. Preparation of 1-pentyloxy-2-propyl-benzene (1-pentyloxy-2-propyl-benzene)

2-hydroxy-benzoic Acid instead of 2-ethyl-1-pentyl-2-propyl having the following physical data, and are synthesized to the same manner as in Example 4 except for using the phenol-benzene.

FAB mass : 207 [M+H] ⁺

Example 26. Preparation of 2-ethylhexanoic acid 2-propyl-phenyl ester (2-ethylhexanoic acid 2-propyl-phenyl ester)

2-ethylhexanoic acid 2-propyl-phenyl ester synthesized in the same manner as in Example 24 and having the following physical properties except that 2-propyl-benzene was used instead of 1-(2-hydroxy-phenyl)-ethanone was obtained.

FAB mass : 263 [M+H] ⁺

Example 27. Preparation of 2-ethylhexanoic acid 3-propyl-phenyl ester (2-ethylhexanoic acid 3-propyl-phenyl ester)

2-ethylhexanoic acid 3-propyl-phenyl ester synthesized in the same manner as in Example 24 and having the following physical properties except that 3-propyl-benzene was used instead of 1-(2-hydroxy-phenyl)-ethanone was obtained.

FAB mass : 263 [M+H] ⁺

Example 28. Preparation of 2-hydroxy benzoic acid 2-ethylhexyl ester

In a two-necked round flask at room temperature, 10 mmol of 2-hydroxy benzoic acid was added, and then 50 ml of toluene was added. After 0.1 mmol of sulfuric acid was added as a catalyst, 12 mmol of 2-ethylhexanol was slowly added dropwise. Upon completion of the dropwise addition, the mixture was refluxed under a Dean-stack apparatus and reacted for 12 hours. 500ml of purified water was added to the reaction product, and extraction was performed using 100ml of n-hexane. The hexane layer was dried under reduced pressure and then separated and purified using silica gel column chromatography (ethyl acetate: hexane = 1:10). 2-Hydroxybenzoic acid 2-ethylhexyl ester was obtained and identified using fast atomic bombardment mass spectrometry (hereinafter referred to as FAB-MS).

FAB mass : 251 [M+H] ⁺

Example 29. Preparation of 3-hydroxy benzoic acid 2-ethylhexyl ester

The synthesis was performed in the same manner as in Example 28 except that 3-hydroxybenzoic acid was used instead of 2-hydroxybenzoic acid to obtain 3-hydroxybenzoic acid 2-ethylhexyl ester having the following physical properties.

FAB mass : 251 [M+H] ⁺

Experimental Example 1. Measurement of melanin production inhibitory effect

The compounds prepared according to the methods described in Examples 1 to 29 and hydroquinone were added to the culture medium of B-16 mouse melanoma cells to test the whitening effect at the cellular level. (Lotan R ., Lotan D. Cancer Res., 40 , pp.3345-3350, 1980). The final concentrations of the compounds prepared above were added to the culture medium of B-16 melanoma cells so that the final concentrations were 5 μg/ml and 10 μg/ml, respectively, and cultured for 3 days, then the cells were treated with trypsin and cultured After removing from the container and centrifuging, melanin was extracted. 1 ml of 1 N sodium hydroxide solution was added to the extract, boiled for 10 minutes to dissolve melanin, and then the amount of melanin produced by measuring the absorbance at 475 nanometers (nm) using a spectrophotometer was measured per unit cell number (10 ⁶ cells) absorbance (repeated 3 times). Melanin production relative to the control was calculated as the inhibition rate (%) and the results are shown in Table 1.

All of the above compounds showed a melanogenesis inhibitory effect comparable to that of hydroquinone on melanoma cells in cultured mice. Hydroquinone shows a strong melanogenesis inhibitory effect at a low concentration, but the cytotoxicity is so severe that the test cannot be performed at more than 1 μg/ml, whereas the compounds do not show cytotoxicity even at a concentration of 20 μg/ml, so higher melanin production than hydroquinone It can have an inhibitory effect.

Inhibitory effect on melanin production at the cellular level sample Concentration (ug/ml) Inhibition rate (%) control - - hydroquinone One 48 5 extinct material of example 1 5 31 20 46 material of example 2 5 41 20 52 material of example 3 5 45 20 64 material of example 4 5 54 20 65 material of example 5 5 52 20 67 material of example 6 5 41 20 52 material of example 7 5 22 20 35 material of example 8 5 27 20 42 material of example 9 5 29 20 48 material of example 10 5 38 20 54 material of example 11 5 49 20 62 material of example 12 5 46 20 61 material of example 13 5 29 20 41 material of example 14 5 21 20 32 material of example 15 5 39 20 57 material of example 16 5 41 20 52 material of example 17 5 38 20 52 material of example 18 5 42 20 71 material of example 19 5 38 20 59 material of example 20 5 24 20 41 material of example 21 5 25 20 45 material of example 22 5 19 20 37 material of example 23 5 27 20 41 material of example 24 5 19 20 38 material of example 25 5 16 20 31 material of example 26 5 24 20 35 material of example 27 5 23 20 41 material of example 28 5 27 20 39 material of example 29 5 26 20 37

Preparation Example 1. Preparation of softened lotion

Formulation 1 and Comparative Formulation 1 were prepared with the composition shown in Table 2 below.

Composition (wt%) Formulation 1 Comparative Formulation 1 a b c d material of example 4 0.1 - - - - material of example 11 - 0.1 - - - material of example 28 - - 0.1 - - material of example 29 - - - 0.1 - ethanol 10.0 10.0 10.0 10.0 10.0 Polyoxyethylene hydrogenated castor oil 1.0 1.0 1.0 1.0 1.0 methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 1,3-butylene glycol 6.0 6.0 6.0 6.0 6.0 incense appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 2. Preparation of nutrient lotion

Formulation 2 and Comparative Formulation 2 were prepared with the composition shown in Table 3 below.

Composition (wt%) Formulation 2 Comparative Formulation 2 a b c d material of example 4 0.1 - - - - material of example 11 - 0.1 - - - material of example 28 - - 0.1 - - material of example 29 - - - 0.1 - Polyoxyethylene hydrogenated castor oil 1.0 1.0 1.0 1.0 1.0 methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 glycerin 6.0 6.0 6.0 6.0 6.0 1,3-butylene glycol 5.0 5.0 5.0 5.0 5.0 Carbomer 0.2 0.2 0.2 0.2 0.2 triethanolamine 0.3 0.3 0.3 0.3 0.3 propylene glycol 5.0 5.0 5.0 5.0 5.0 ethanol 3.2 3.2 3.2 3.2 3.2 Carboxyvinyl Polymer 0.1 0.1 0.1 0.1 0.1 incense appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 3. Preparation of cream

Formulation 3 and Comparative Formulation 3 were prepared with the composition shown in Table 4 below.

Composition (wt%) Formulation 3 Comparative Formulation 3 a b c d material of example 4 0.1 - - - - material of example 11 - 0.1 - - - material of example 28 - - 0.1 - - material of example 29 - - - 0.1 - cetanol 2.0 2.0 2.0 2.0 2.0 PEG-20 1.0 1.0 1.0 1.0 1.0 sorbitan monostearate 1.0 1.0 1.0 1.0 1.0 mineral oil 10.0 10.0 10.0 10.0 10.0 trioctanoate 5.0 5.0 5.0 5.0 5.0 triethanolamine 0.5 0.5 0.5 0.5 0.5 Carbomer 0.2 0.2 0.2 0.2 0.2 glycerin 5.0 5.0 5.0 5.0 5.0 propylene glycol 3.0 3.0 3.0 3.0 3.0 antiseptic appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount incense appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 4. Preparation of ointment for external use on the skin

Formulation 4 and Comparative Formulation 4 were prepared with the composition shown in Table 5 below.

Composition (wt%) Formulation 4 Comparative Formulation 4 a b c d material of example 4 0.1 - - - - material of example 11 - 0.1 - - - material of example 28 - - 0.1 - - material of example 29 - - - 0.1 - diethyl sebacate 8.0 8.0 8.0 8.0 8.0 brazing 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene oleyl ether phosphate 6.0 6.0 6.0 6.0 6.0 sodium benzoate appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount vaseline to 100 to 100 to 100 to 100 to 100

manufacturing example 5. Preparation of Essence

Formulation 5 and Comparative Formulation 5 were prepared with the composition shown in Table 6 below.

Composition (wt%) Formulation 5 Comparative Formulation 5 a b c d material of example 4 0.5 - - - - material of example 11 - 0.5 - - - material of example 28 - - 0.5 - - material of example 29 - - - 0.5 - propylene glycol 10.0 10.0 10.0 10.0 10.0 glycerin 10.0 10.0 10.0 10.0 10.0 Sodium hyaluronate aqueous solution (1%) 5.0 5.0 5.0 5.0 5.0 ethanol 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene hydrogenated castor oil 1.0 1.0 1.0 1.0 1.0 methyl paraoxybenzoate 0.1 0.1 0.1 0.1 0.1 Carbomer 0.4 0.4 0.4 0.4 0.4 incense appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount Purified water to 100 to 100 to 100 to 100 to 100

Preparation Example 6. Preparation of pack

Formulation 6 and Comparative Formulation 6 were prepared with the composition shown in Table 7 below.

Composition (wt%) Formulation 6 Comparative Formulation 6 a b c d material of example 4 0.1 - - - - material of example 11 - 0.1 - - - material of example 28 - - 0.1 - - material of example 29 - - - 0.1 - glycerin 5.0 5.0 5.0 5.0 5.0 propylene glycol 4.0 4.0 4.0 4.0 4.0 polyvinyl alcohol 15.0 15.0 15.0 15.0 15.0 ethanol 8.0 8.0 8.0 8.0 8.0 Polyoxyethylene hydrogenated castor oil 1.0 1.0 1.0 1.0 1.0 Polyoxyethylene oleyl ether phosphate 1.0 1.0 1.0 1.0 1.0 methyl paraoxybenzoate 0.2 0.2 0.2 0.2 0.2 incense appropriate amount appropriate amount appropriate amount appropriate amount appropriate amount Purified water to 100 to 100 to 100 to 100 to 100

Experimental Example 2. Confirmation of pigmentation inhibitory effect

In order to verify the pigmentation inhibitory effect of Formulations 1 to 6 and Comparative Formulations 1 to 6 prepared in Preparation Examples 1 to 6, an experiment was conducted in the following manner.

Eighty healthy subjects were selected, and aluminum foil with 7 holes of 7 mm in diameter was attached to the lower arm of both arms in two rows, and 60mJ was used using an artificial sunlight irradiation device (ORIEL solar simulator 1000W) at a distance of 10cm from the arm. /cm ² The amount of light was irradiated. Before irradiation, the irradiation site was well washed with 70% ethanol aqueous solution. Formulations 1 to 6 and Comparative Formulations 1 to 6 were applied as a pair in the same row twice a day from 3 days before irradiation until 8 weeks after irradiation. The pack agent of Formulation 6 and Comparative Formulation 6 was peeled off 15 minutes after application.

The panel was divided into 20 groups in 1 group and the test was conducted in 4 groups. For the determination of the whitening effect, the degree of pigmentation of the formulations and the comparative formulations was visually determined for each, and the degree of suppression of the pigmentation of the formulation compared to the comparative formulation was evaluated in three stages: clear effect, effective, and no difference. , the results are shown in Table 8 below.

As shown in Table 8, the cosmetics of formulations 1 to 6 containing the substances of the present invention exhibited excellent skin whitening effect compared to conventional cosmetics.

pigmentation inhibitory effect test substance distinct effect (persons) Effective (persons) No difference (persons) Comparative Formulation 1 0 One 19 Formulation 1 a 5 8 7 b 5 9 6 c 4 9 7 d 4 9 7 Comparative Formulation 2 0 3 17 Preparation 2 a 6 9 5 b 4 10 6 c 6 9 5 d 6 9 5 Comparative Formulation 3 0 2 18 Formulation 3 a 7 9 4 b 8 6 6 c 7 7 6 d 7 7 6 Comparative Formulation 4 0 2 18 Formulation 4 a 5 10 5 b 7 9 4 c 7 8 5 d 7 8 5 Comparative Formulation 5 0 3 17 Formulation 5 a 5 8 7 b 7 6 7 c 8 7 5 d 8 6 6 Comparative Formulation 6 0 2 18 Formulation 6 a 8 7 5 b 7 6 7 c 7 9 4 d 7 9 4

Claims (9)

A cosmetic composition for skin whitening comprising a derivative of a cyclic compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof as an active ingredient,
The active ingredient is 2-ethoxy benzoic acid ethyl ester, 2-propoxy benzoic acid propyl ester, 2-butoxy benzoic acid butyl ester, 2-pentyloxy benzoic acid pentyl ester, 2-hexyloxy benzo Acid hexyl ester, 2-octyloxy benzoic acid octyl ester, 2-decyloxy benzoic acid decyl ester, 3-ethoxy benzoic acid ethyl ester, 3-propoxy benzoic acid propyl ester, 3-butoxy Benzoic acid butyl ester, 3-pentyloxy benzoic acid pentyl ester, 3-hexyloxy benzoic acid hexyl ester, 3-octyloxy benzoic acid octyl ester, 3-decyloxy benzoic acid decyl ester, 5- Acetyl-2-pentyloxy benzoic acid pentyl ester, 1-pentyloxy-2-naphthoic acid pentyl ester, 3-pentyloxy-2-naphthoic acid pentyl ester, 3-pentyloxy-4-pyridinecarboxylic acid pentyl ester Ester, 3-pentyloxy-quinoline-4-carboxylic acid pentyl ester, 1-(2-pentyloxy-phenyl)-ethanone, 1-(3-pentyloxy-phenyl)-ethanone, 1-(3- Pentyloxy-naphthalen-2-yl)-ethanone, acetic acid 2-acetyl-phenyl ester, 2-ethylhexanoic acid 2-acetyl-phenyl ester, 1-pentyloxy-2-propyl-benzene, 2-ethyl Hexanoic acid 2-propyl-phenyl ester, 2-ethylhexanoic acid 3-propyl-phenyl ester, 2-hydroxybenzoic acid 2-ethylhexyl ester, and 3-hydroxybenzoic acid 2-ethylhexyl ester A cosmetic composition for skin whitening, characterized in that it is one kind of compound selected from the group.

in the above formula

is derived from an aromatic ring compound, and B is hydrogen, oxo (oxo, =O), amino (amino, -NH ₂ ), imino (imino, =NH), C ₁ to C ₁₀ saturated or unsaturated straight chain or a branched alkyl group, alkoxy, monoalkylamino group, or dialkylamino group,
C _n , C _n+1 and C _n+2 are three adjacent carbons present in the cyclic compound, and n is a positive integer.
R ₁ is hydrogen, hydroxy, saturated or unsaturated straight-chain or branched alkyl group or alkoxy group,
X is hydrogen and Y is hydroxy, or X is hydroxy and Y is hydrogen.
R ₂ , R _{3 ,} R ₄ and R ₅ are each independently at least one selected from hydrogen, alkyl, alkoxy, acyloxy, acyloxymethyl, oxo, hydroxy, vinyl, nitrile, carboxyaldehyde, carbonitrile, and aldehyde is a substituent.
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