KR100506423B1 - Novel benzoic acid derivatives, preparation method thereof and whitening cosmetic composition containing same - Google Patents
Novel benzoic acid derivatives, preparation method thereof and whitening cosmetic composition containing same Download PDFInfo
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- KR100506423B1 KR100506423B1 KR1019980017062A KR19980017062A KR100506423B1 KR 100506423 B1 KR100506423 B1 KR 100506423B1 KR 1019980017062 A KR1019980017062 A KR 1019980017062A KR 19980017062 A KR19980017062 A KR 19980017062A KR 100506423 B1 KR100506423 B1 KR 100506423B1
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Abstract
하기 일반식(I)로 표시되는 신규한 벤조산 유도체, 그의 제조방법 및 그를 함유하는 화장료 조성물에 관한 것으로서, 하기 일반식(I)의 벤조산 유도체 및 그를 함유하는 화장료 조성물은 피부의 멜라닌 색소 생성을 억제하여 피부의 흑화, 기미 등을 방지할 수 있다.The present invention relates to a novel benzoic acid derivative represented by the following general formula (I), a preparation method thereof, and a cosmetic composition containing the same, wherein the benzoic acid derivative of the following general formula (I) and a cosmetic composition containing the same inhibit the production of melanin pigment in the skin. This can prevent blackening and blemishes of the skin.
일반식(I)Formula (I)
Description
본 발명은 하기 일반식 (I)로 표시되는 신규한 벤조산 유도체에 관한 것으로서, 더욱 상세하게는 불포화 알킬기가 오르토 위치에 치환된 벤조산 유도체, 그의 제조방법 및 그를 함유하는 화장료 조성물에 관한 것이다.The present invention relates to a novel benzoic acid derivative represented by the following general formula (I), and more particularly to a benzoic acid derivative in which an unsaturated alkyl group is substituted at the ortho position, a preparation method thereof, and a cosmetic composition containing the same.
상기 식에서 R은 적어도 하나의 이중결합을 포함하는 탄소수 6내지 20의 불포화 알킬기(여기서 이중결합은 cis형임)를 나타낸다.In the formula, R represents an unsaturated alkyl group having 6 to 20 carbon atoms including at least one double bond, wherein the double bond is cis type.
희고 고운 피부를 갖고자 하는 것은 모든 사람의 한결같은 소망이다. 사람의 피부색은 피부내 멜라닌(melanin)의 농도와 분포에 따라 유전적으로 결정되나, 태양 자외선이나 피로, 스트레스 등의 환경적 또는 생리적 조건에 의해서도 영향을 받는다. 최근 화장품 업계에서는 피부 미백제가 관심의 대상이 되고 있는데, 이러한 피부 미백제는 태양 자외선이나 피로, 스트레스 등의 환경적 또는 생리적 조건에 따라서 발생하는 멜라닌의 과다한 생성을 억제하여 피부의 흑화나 기미, 주근깨 등의 발생을 억제하고 흰 피부를 유지하는 기능을 하는 것이다.It is everyone's constant desire to have white, fair skin. Human skin color is genetically determined by the concentration and distribution of melanin in the skin, but is also influenced by environmental or physiological conditions such as solar ultraviolet rays, fatigue and stress. Recently, in the cosmetics industry, skin whitening agents have been of interest, and such skin whitening agents suppress excessive production of melanin, which occurs according to environmental or physiological conditions such as sun ultraviolet rays, fatigue, stress, etc. It is to suppress the occurrence of and to maintain the white skin.
최근, 히데야 안도(Hideya Ando)등은 불포화 지방산이 배양된 쥐의 멜라노마세포(B-16 mouse melanoma cell)에서 멜라닌 생성 억제 작용을 한다는 것을 보고 (Fragrance Journal, 1995, 145∼150쪽 참조)하여, 이러한 불포화 지방산이 피부 미백제로 사용될 수 있는 가능성을 제시한 바 있다.Recently, Hideya Ando et al. Reported that unsaturated fatty acids inhibit melanin production in B-16 mouse melanoma cells (Fragrance Journal, 1995, pp. 145-150). This suggests the possibility that these unsaturated fatty acids can be used as skin whitening agents.
이에 본 발명자들은 상기 불포화 지방산의 구조적인 변환체들을 조사하는 과정에서 불포화 지방산의 불포화된 알킬기를 벤조산에 치환한 물질이 불포화 지방산보다 배양된 쥐의 멜라노마 세포(B-16 mouse melanoma cell)에서 멜라닌 생성 억제 작용이 높다는 것을 발견하고 본 발명을 완성하게 되었다. 따라서 본 발명은 피부의 멜라닌 색소 생성을 억제하여 피부의 흑화, 기미 등을 방지할 수 있는 신규한 벤조산 유도체, 이의 제조방법 및 이를 함유하는 미백 화장료 조성물을 제공하는 것을 목적으로 한다.Accordingly, the present inventors found that melanin in a mouse melanoma cell (B-16 mouse melanoma cell) in which a substance substituted with an unsaturated alkyl group of an unsaturated fatty acid to benzoic acid in the course of examining the structural transformants of the unsaturated fatty acid was cultured than an unsaturated fatty acid. The present invention has been found to have a high production inhibitory effect. Accordingly, an object of the present invention is to provide a novel benzoic acid derivative, a method for preparing the same, and a whitening cosmetic composition containing the same, which can prevent melanin pigmentation of the skin and prevent blackening and blemishes of the skin.
본 발명은 하기 일반식(I)과 같이 불포화 알킬기가 오르토 위치에 치환된 벤조산 유도체 및 상기 벤조산 유도체를 포함하는 미백 화장료 조성물을 제공한다. The present invention provides a whitening cosmetic composition comprising the benzoic acid derivative having the unsaturated alkyl group substituted at the ortho position and the benzoic acid derivative as shown in the following general formula (I).
일반식(I )Formula (I)
(상기 식에서 R은 적어도 하나의 이중결합을 포함하는 탄소수 6내지 20의 불포화 알킬기(여기서 이중결합은 cis형임)를 나타낸다.)(Wherein R represents an unsaturated alkyl group having 6 to 20 carbon atoms containing at least one double bond, wherein the double bond is of cis type).
또한, 본 발명은 하기 일반식(III)의 화합물을 마그네슘과 반응시켜 유기 마그네슘 중간체를 얻은 다음, 이를 하기 일반식(II)의 화합물과 촉매의 혼합용액에 첨가하여 하기 일반식(IV)의 화합물을 얻고, 얻어진 일반식(IV)의 화합물을 금속과 반응시킨 후, 이를 이산화탄소와 반응시킴을 특징으로 하는 상기 일반식 (I)의 벤조산 유도체의 제조방법을 제공한다.In addition, the present invention is obtained by reacting a compound of the general formula (III) with magnesium to obtain an organic magnesium intermediate, and then adding it to a mixed solution of the compound of the general formula (II) and a catalyst of the general formula (IV) The present invention provides a process for preparing the benzoic acid derivative of formula (I), wherein the compound of formula (IV) is reacted with a metal and then reacted with carbon dioxide.
일반식(II)Formula (II)
일반식(III) General formula (III)
일반식(IV)General formula (IV)
상기 식에서 R은 전술한 바와 같다.In which R is as described above.
이하, 본 발명을 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail.
본 발명의 신규한 벤조산 유도체는 불포화 알킬기가 벤조산의 오르토 위치에 치환된 것으로서, 상기 일반식(I)과 같은 구조를 가진다. 여기서 상기 R은 적어도 하나의 cis형 이중결합을 포함하는 탄소수 6내지 20의 불포화 알킬기를 나타내는 것으로서, 바람직하기로는 CH3(CH2)7CH=CH(CH2)7CH2- (이중결합은 cis형 임)로 표시되는 올레일(Oleyl)기, CH3(CH2)4CH=CHCH2CH=CH(CH2)7CH2- (이중결합은 cis형 임)로 표시되는 리놀레일(Linoleyl)기 또는 CH3(CH2)5CH=CH(CH2)7CH2- (이중결합은 cis형임)로 표시되는 팔미톨레일(Palmitoleyl)기 이다.The novel benzoic acid derivatives of the present invention are those in which an unsaturated alkyl group is substituted at the ortho position of benzoic acid and has the same structure as in general formula (I). Wherein R represents an unsaturated alkyl group having 6 to 20 carbon atoms including at least one cis-type double bond, preferably CH 3 (CH 2 ) 7 CH = CH (CH 2 ) 7 CH 2- (double bond is oleyl group represented by cis type, and linoleyl represented by CH 3 (CH 2 ) 4 CH = CHCH 2 CH = CH (CH 2 ) 7 CH 2 − (double bond is cis type) Linoleyl) or CH 3 (CH 2 ) 5 CH = CH (CH 2 ) 7 CH 2- (double bond is cis type) is a Palmitoleyl (Palmitoleyl) group.
상기 벤조산 유도체를 제조하기 위하여는, 먼저 상기 일반식(III)의 화합물을 마그네슘과 30분에서 2시간 동안 반응시켜 유기 마그네슘 중간체(BrMg-R)를 얻은 다음, 이를 일반식(II)의 화합물과 촉매의 혼합용액에 첨가하고 1 내지 12시간 동안 교반하여 일반식(IV)의 화합물을 얻는다. 상기 반응에 사용되는 용매로는 테트라히드로푸란, 1, 4-디옥산, 디에틸에테르 등을 사용할 수 있으나, 테트라히드로푸란을 사용하는 것이 가장 바람직하며, 상기 촉매로는 Li2CuCl4, CuI, CuCl중에서 선택되는 하나 이상의 구리화합물을 사용하는 것이 바람직하다. 이와 같이 얻어진 일반식(IV)의 화합물은 정제되거나 정제되지 않은 상태로 다음 반응에 투입된다.In order to prepare the benzoic acid derivative, first, the compound of formula (III) is reacted with magnesium for 30 minutes to 2 hours to obtain an organic magnesium intermediate (BrMg-R), and then the compound of formula (II) It is added to the mixed solution of the catalyst and stirred for 1 to 12 hours to obtain a compound of formula (IV). Tetrahydrofuran, 1, 4-dioxane, diethyl ether and the like may be used as the solvent used in the reaction, but tetrahydrofuran is most preferably used, and Li 2 CuCl 4 , CuI, Preference is given to using at least one copper compound selected from CuCl. The compound of formula (IV) thus obtained is charged to the next reaction in a purified or unpurified state.
다음으로 일반식(IV)의 화합물을 마그네슘, 리튬 등의 금속(알킬리튬 등의 금속화합물을 포함한다.)과 30분에서 2시간 동안 반응시켜 브롬 라디칼을 마그네슘 또는 리튬 등의 금속으로 치환한 다음, 이 혼합액을 냉각한 후 이산화탄소를 첨가하고 2분 내지 2시간동안 교반하여 일반식(I)의 벤조산 유도체를 제조한다. 상기 반응에 사용되는 용매로는 테트라히드로푸란, 1, 4-디옥산, 디에틸에테르 등을 사용할 수 있으나, 테트라히드로푸란을 사용하는 것이 가장 바람직하다. 또한, 상기 반응들은 -78℃에서 사용되는 용매의 끓는점까지의 온도 범위에서 실시할 수 있으며, 특히 고체 이산화탄소를 첨가할 때는 상기 혼합액을 -78℃로 유지하고, 그후 온도를 용매의 끓는점까지 상승시키면서 반응시키는 것이 바람직하다. 또한, 상기 반응에 소요되는 시간들은 반응의 수율 및 효율을 적절히 나타내도록 설정된 것이며, 일반적으로 반응 시간이 상기 시간 미만이면 반응이 완전히 진행되지 않으며, 상기 시간을 초과하여도 반응 수율이 더 이상 향상되지 않는다. 상기 반응에 있어서, 일반식(II) 및 일반식(III)의 화합물로는 브롬 치환체뿐만 아니라, 염소 또는 요오드 등의 할로겐치환체 등도 사용할 수 있으나, 염소 치환체의 경우에는 반응성이 떨어지며, 요오드 치환체는 치환체 자체가 불안정한 단점이 있다.Next, the compound of general formula (IV) is reacted with a metal such as magnesium or lithium (including a metal compound such as alkyl lithium) for 30 minutes to 2 hours to replace the bromine radical with a metal such as magnesium or lithium. After cooling the mixture, carbon dioxide was added and stirred for 2 minutes to 2 hours to prepare a benzoic acid derivative of formula (I). Tetrahydrofuran, 1, 4-dioxane, diethyl ether and the like may be used as the solvent used in the reaction, but tetrahydrofuran is most preferably used. In addition, the reactions can be carried out in a temperature range up to the boiling point of the solvent used at -78 ℃, in particular when the solid carbon dioxide is added to maintain the mixture at -78 ℃, then raising the temperature to the boiling point of the solvent It is preferable to make it react. In addition, the time required for the reaction is set to properly indicate the yield and efficiency of the reaction, and in general, if the reaction time is less than the time, the reaction does not proceed completely, and the reaction yield is no longer improved even after the time. Do not. In the above reaction, as the compound of general formula (II) and general formula (III), not only a bromine substituent, but also a halogen substituent such as chlorine or iodine may be used, but in the case of a chlorine substituent, the reactivity is inferior, and the iodine substituent is a substituent It has its own drawbacks.
이와 같이 합성된 일반식(I)의 벤조산 유도체와 통상적인 화장품 담체를 혼합하여 화장용 크림, 유연화장수, 엣센스, 화장 팩 및 영양화장수 등의 화장료 등을 제조하거나 피부 외용 연고를 제조한다. 상기 화장품 담체로는 통상적으로 사용되는 디에틸세바케이트, 스테아린산, 글리세린 등을 사용할 수 있으나 이에 한정되는 것은 아니다.The benzoic acid derivatives of general formula (I) thus synthesized are mixed with conventional cosmetic carriers to prepare cosmetics such as cosmetic creams, soft cosmetics, essences, cosmetic packs and nourishing cosmetics, or to prepare external skin ointments. As the cosmetic carrier, diethyl sebacate, stearic acid, glycerin, etc. which are commonly used may be used, but are not limited thereto.
이때 화장료나 피부 외용 연고 중의 상기 벤조산 유도체의 함량은 0.001 내지 10중량%이고, 화장품 담체등 나머지 성분의 양이 90∼99.999중량%인 것이 바람직한데, 상기 함량이 0.001중량% 미만이면 피부의 미백효과가 충분히 나타나지 않고, 10중량% 이상이면 과잉의 벤조산 유도체를 사용하는 만큼 피부미백효과가 상승되지 않을 뿐만 아니라, 화장료의 다른 화장 효과를 떨어뜨린다.At this time, the content of the benzoic acid derivative in the cosmetic or skin ointment is 0.001 to 10% by weight, the amount of the remaining components such as cosmetic carrier is preferably from 90 to 99.9% by weight, if the content is less than 0.001% by weight of the skin whitening effect Is not sufficiently exhibited, and if it is 10% by weight or more, the skin whitening effect is not increased as much as the excess benzoic acid derivative is used, and the other cosmetic effects of the cosmetic are lowered.
이하, 본 발명을 실시예에 의거하여 구체적으로 설명한다. 그러나, 이들 실시예는 본 발명에 대한 이해를 돕기 위한 것으로서, 본 발명이 이에 한정되는 것은 아니다.EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated concretely based on an Example. However, these examples are intended to help the understanding of the present invention, the present invention is not limited thereto.
[실시예1] Example 1
올레일 브로미드(3.0g)와 마그네슘(1.0g)을 테트라히드로푸란(40ml)에 넣고 1시간 동안 환류시킨다. 이 혼합물을 실온으로 냉각시킨 후, 0℃로 냉각한 2-브로모 벤질 브로마이드(1.5g), Li2CuCl4(0.O5g)와 테트라히드로푸란(4Oml)으로 이루어진 혼합용액에 첨가하고 상온에서 10시간 교반시킨다. 증류수(50ml)를 첨가하고 테트라히드로푸란을 감압제거한 후 염화메틸렌(50ml)으로 추출하고, 포화 소금물로 세척한 후, 무수 망초로 탈수시키고 용매를 감압제거 하였다. 여기에 테트라히드로푸란(40ml)을 넣고 마그네슘(1.0g)을 넣은 후 1시간 환류시킨 다음, 이 혼합물을 -78℃로 냉각한 후 고체 이산화탄소(드라이 아이스, 2.0g)를 넣고 1시간 교반시킨다. 증류수(40ml)를 첨가하고 테트라히드로푸란을 감압제거한 후, 염화메틸렌(40ml)으로 추출하고, 포화 소금물로 세척한 후, 무수 망초로 탈수시키고 용매를 감압제거한다. 컬럼 크로마토그래피로 분리 정제하여 조산(구조식(Ⅴ) 1.5g (수율 : 64%)을 얻었으며, 도 1에 상기 구조식(V)의 화합물의 NMR챠트를 도시하였다.Oleyl bromide (3.0 g) and magnesium (1.0 g) were added to tetrahydrofuran (40 ml) and refluxed for 1 hour. After the mixture was cooled to room temperature, it was added to a mixed solution of 2-bromo benzyl bromide (1.5 g), Li 2 CuCl 4 (0.O5 g), and tetrahydrofuran (40 mL), cooled to 0 ° C., at room temperature. Stir for 10 hours. Distilled water (50ml) was added, tetrahydrofuran was removed under reduced pressure, extracted with methylene chloride (50ml), washed with saturated brine, dehydrated with anhydrous forget-me-not and the solvent was removed under reduced pressure. Tetrahydrofuran (40 ml) was added thereto, magnesium (1.0 g) was added thereto, and the mixture was refluxed for 1 hour. After cooling the mixture to -78 ° C, solid carbon dioxide (dry ice, 2.0 g) was added thereto and stirred for 1 hour. Distilled water (40 ml) was added, tetrahydrofuran was removed under reduced pressure, extracted with methylene chloride (40 ml), washed with saturated brine, dehydrated with anhydrous forget-me-not and the solvent was removed under reduced pressure. Separation and purification by column chromatography Crude acid (formula (V) 1.5g (yield: 64%) was obtained and FIG. 1 shows an NMR chart of the compound of formula (V)).
구조식(V)Structural Formula (V)
[실시예 2] Example 2
리놀레일 브로미드(3.0g)와 마그네슘(1.0g)을 테트라히드로푸란(40ml)에 넣고 1시간 동안 환류시킨다. 이 혼합물을 실온으로 냉각시킨 후, 0℃로 냉각한 2-브로모 벤질 브로마이드(1.5g), Li2CuCl4(0.O5g)와 테트라히드로푸란(4Oml)으로 이루어진 혼합용액에 첨가하고 상온에서 10시간 교반시킨다. 증류수(50ml)를 첨가하고 테트라히드로푸란을 감압제거한 후 염화메틸렌(50ml)으로 추출하고, 포화 소금물로 세척한 후, 무수 망초로 탈수시키고 용매를 감압제거하였다. 여기에 테트라히드로푸란(40ml)을 넣고 마그네슘(1.0g)을 넣은 후 1시간 환류시킨 다음, 이 혼합물을 -78℃로 냉각한 후 고체 이산화탄소(드라이 아이스, 2.0g)를 넣고 1시간 교반시킨다. 증류수(40ml)를 첨가하고 테트라히드로푸란을 감압제거한 후 염화메틸렌(40ml)으로 추출하고, 포화 소금물로 세척한 후, 무수 망초로 탈수시키고 용매를 감압제거한다. 컬럼 크로마토그래피로 분리 정제하여 1.6g (수율 : 70%)을 얻었으며, 도 2에 상기 구조식(VI)의 화합물의 NMR챠트를 도시하였다.Linoleyl bromide (3.0 g) and magnesium (1.0 g) were added to tetrahydrofuran (40 ml) and refluxed for 1 hour. After the mixture was cooled to room temperature, it was added to a mixed solution of 2-bromo benzyl bromide (1.5 g), Li 2 CuCl 4 (0.O5 g), and tetrahydrofuran (40 mL), cooled to 0 ° C., at room temperature. Stir for 10 hours. Distilled water (50 ml) was added, tetrahydrofuran was removed under reduced pressure, extracted with methylene chloride (50 ml), washed with saturated brine, dehydrated with anhydrous forget-me-not and the solvent was removed under reduced pressure. Tetrahydrofuran (40 ml) was added thereto, magnesium (1.0 g) was added thereto, and the mixture was refluxed for 1 hour. After cooling the mixture to -78 ° C, solid carbon dioxide (dry ice, 2.0 g) was added thereto and stirred for 1 hour. Distilled water (40 ml) was added, tetrahydrofuran was removed under reduced pressure, extracted with methylene chloride (40 ml), washed with saturated brine, dehydrated with anhydrous forget-me-not and the solvent was removed under reduced pressure. Separation and purification by column chromatography 1.6 g (yield: 70%) were obtained, and an NMR chart of the compound of formula VI was shown in FIG. 2.
구조식(VI)Structural Formula (VI)
[실시예 3] Example 3
팔미톨레일 브로미드(3.5g)와 마그네슘(1.0g)을 테트라히드로푸란(40ml)에 넣고 1시간 동안 환류시킨다. 이 혼합물을 실온으로 냉각시킨 후, 0℃로 냉각한 2-브로모 벤질 브로마이드(1.5g), Li2CuCl4(O.O5g)와 테트라히드로푸란(4Oml) 혼합용액에 첨가하고 상온에서 10시간 교반시킨다. 증류수(50ml)를 첨가하고 테트라히드로푸란을 감압제거한 후 염화메틸렌(50ml)으로 추출하고, 포화 소금물로 세척한후, 무수 망초로 탈수시키고 용매를 감압제거하였다. 여기에 테트라히드로푸란(40ml)을 넣고 마그네슘(1.0g)을 넣은 후 1시간 환류시킨 다음, 이 혼합물을 -78℃로 냉각한 후 고체 이산화탄소(드라이 아이스, 2.0g)를 넣고 1시간 교반시킨다. 증류수(40ml)를 첨가하고 테트라히드로푸란을 감압제거한 후 염화메틸렌(40ml)으로 추출하고, 포화 소금물로 세척한 후, 무수 망초로 탈수시키고 용매를 감압제거한다. 컬럼 크로마토그래피로 분리 정제하여 1.6g (수율 : 74%)을 얻었다.Palmitoleyl bromide (3.5 g) and magnesium (1.0 g) were added to tetrahydrofuran (40 ml) and refluxed for 1 hour. The mixture was cooled to room temperature, and then added to a mixture of 2-bromo benzyl bromide (1.5 g), Li 2 CuCl 4 (O 5 g) and tetrahydrofuran (4O ml) cooled to 0 ° C., at room temperature for 10 hours. Stir. Distilled water (50ml) was added, tetrahydrofuran was removed under reduced pressure, extracted with methylene chloride (50ml), washed with saturated brine, dehydrated with anhydrous forget-me-not and the solvent was removed under reduced pressure. Tetrahydrofuran (40 ml) was added thereto, magnesium (1.0 g) was added thereto, and the mixture was refluxed for 1 hour. After cooling the mixture to -78 ° C, solid carbon dioxide (dry ice, 2.0 g) was added thereto and stirred for 1 hour. Distilled water (40 ml) was added, tetrahydrofuran was removed under reduced pressure, extracted with methylene chloride (40 ml), washed with saturated brine, dehydrated with anhydrous forget-me-not and the solvent was removed under reduced pressure. Separation and purification by column chromatography 1.6g (yield: 74%) was obtained.
구조식(VII)Structural Formula (VII)
[실험예 1]Experimental Example 1
상기 실시예 1∼3에서 얻어진 화합물을 쥐의 멜라노마 세포(B16 mouse melanoma cell)의 배양액에 첨가하여 세포수준에서의 미백효과를 실험하였다(Lotan R., Lotan D. Cancer Res. 40 : 3345-3350, 1980 참조). 실시예 1∼3에서 얻어진 화합물과 올레산, 리놀산, 하이드로퀴논을 각각 쥐 멜라노마 (B16 melanoma cell) 세포의 배양 배지에 첨가하여 3일간 배양한 후 세포들을 트립신(trypsin) 처리하여 배양용기로 부터 떼어내 원심분리한 후 멜라닌을 추출하였다. 이것에 수산화나트륨 용액(1N 농도) 1ml를 가하여 1O분간 끓여 멜라닌을 녹이고 분광 광도계를 이용, 400나노미터(nm)에서 흡광도를 측정하여 생성된 멜라닌의 양을 단위 세포수당(1O6 cell)의 흡광도로 나타내는 방법으로 수행하였으며, 대조군에 대한 상대적인 멜라닌 생성량을 저해율(%)로 계산하고 그 결과를 표 1에 나타내었다.The compound obtained in Examples 1 to 3 was added to the culture medium of B16 mouse melanoma cells to test the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res. 40: 3345-). 3350, 1980). The compounds obtained in Examples 1 to 3, oleic acid, linoleic acid, and hydroquinone were added to the culture medium of the rat melanoma (B16 melanoma cell) cells, and then cultured for 3 days, and the cells were trypsinized to separate them from the culture vessel. Melanin was extracted after centrifugation. To this, 1 ml of sodium hydroxide solution (1N concentration) was added, boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nanometers (nm) using a spectrophotometer to determine the amount of melanin produced per unit cell number (10 6 cells). It was carried out by the method shown as, the relative melanin production relative to the control was calculated as the inhibition rate (%) and the results are shown in Table 1.
[표 1] 실시예 1 내지 3, 올레산, 리놀산 및 하이드로퀴논의 세포수준에서의 멜라닌 생성 저해효과 (실험 반복 횟수 = 3)TABLE 1 Examples 1 to 3, melanin production inhibitory effect at the cellular level of oleic acid, linoleic acid and hydroquinone (number of experiments repeated = 3)
상기 결과로부터, 실시예1 내지 3의 화합물은 대조군, 올레산 및 리놀산 등과 비교하여, 세포수준에서의 미백효과가 현저하게 큰 것을 알 수 있다.From the above results, it can be seen that the compounds of Examples 1 to 3 have a significantly greater whitening effect at the cellular level compared to the control, oleic acid and linoleic acid.
[제조예 1] 및 [비교예 1][Production Example 1] and [Comparative Example 1]
실시예 1의 화합물을 함유하는 피부 외용연고 처방예는 다음과 같다.Examples of prescription external skin ointments containing the compound of Example 1 are as follows.
[제조예 2] 및 [비교예 2][Production Example 2] and [Comparative Example 2]
실시예 1의 화합물을 함유하는 화장료 중 크림의 처방예는 다음과 같다.The prescription example of the cream in the cosmetics containing the compound of Example 1 is as follows.
[제조예 3] 및 [비교예 3][Production Example 3] and [Comparative Example 3]
실시예 2의 화합물을 함유하는 화장료중 유연화장수의 처방예는 다음과 같다.The prescription example of the flexible cosmetics in the cosmetics containing the compound of Example 2 is as follows.
[제조예 4] 및 [비교예 4][Production Example 4] and [Comparative Example 4]
실시예 2의 화합물을 함유하는 화장료 중 엣센스의 처방예는 다음과 같다.Prescription examples of essences in the cosmetics containing the compound of Example 2 are as follows.
[제조예 5] 및 [비교예 5]Production Example 5 and Comparative Example 5
실시예 2의 화합물을 함유하는 화장료 중 팩의 처방예는 다음과 같다.The prescription example of the pack in the cosmetics containing the compound of Example 2 is as follows.
[제조예 6] 및 [비교예 6]Production Example 6 and Comparative Example 6
실시예 3의 화합물을 함유하는 화장료 중 영양화장수의 처방예는 다음과 같다.The prescription example of the nutrient cosmetics in the cosmetics containing the compound of Example 3 is as follows.
[실험예 2]Experimental Example 2
건강한 남여 20명을 선정하여 양팔의 하박부에 직경 7mm크기의 구멍이 6개씩 2줄로 파인 알루미늄 호일을 붙이고, 팔에서 1Ocm 떨어진 거리에서 ORIEL solar simulator l00OW를 사용하여 60mJ/cm2의 광량을 조사하였다. 조사전에 70% 에탄올 수용액으로 조사 부위를 잘 세척하였다. 조사하기 3일전부터 조사 후 3주째까지 1일 2회씩 제조예 1-6 및 비교예 1-6에 따라 제조된 기제를 한 쌍으로 같은 줄에 도포하였다. (제조예 5 및 비교예 5의 팩 처방의 경우 도포한 다음 15분 후에 떼어내었다.) 각각에 대하여 제조예와 비교예의 색소침착도를 육안으로 판정하고, 제조예가 비교예에 비해 색소침착을 억제한 정도를 뚜렷한 효과, 효과있음, 차이없음의 3단계로 평가하였으며, 그 결과는 표 2에 나타내었다.20 healthy males and females were placed in the lower arm of each arm with 6 holes of 7mm diameter in two rows of aluminum foil, and 60mJ / cm 2 light was irradiated using ORIEL solar simulator l00OW at a distance of 10cm from the arm. . The irradiation site was washed well with 70% ethanol aqueous solution before irradiation. The bases prepared according to Preparation Example 1-6 and Comparative Example 1-6 were applied twice a day from 3 days before irradiation to 3 weeks after irradiation, in pairs on the same line. (In the case of the pack formulations of Production Example 5 and Comparative Example 5, after the application, 15 minutes after peeling off), the pigmentation degree of the Preparation Example and Comparative Example was visually determined for each, and the Production Example suppressed the pigmentation compared with the Comparative Example. One degree was evaluated in three stages of distinct effects, effects, and no difference, and the results are shown in Table 2.
[표 2] 본 발명의 화합물을 함유한 연고 및 화장료의 색소 침착 저해 효과TABLE 2 Pigmentation inhibitory effect of ointments and cosmetics containing the compound of the present invention
위의 표 2의 결과로부터, 제조예 1-6에 따라 제조된 본 발명의 화합물을 함유한 연고 및 화장료는 피시험자 20명중에서 최소 10명 이상에 대하여 미백효과를 나타내었으며, 특히 많은 양의 화합물이 적용된 제조예 1과 비교예 1의 비교실험에서는 35%가 뚜렷한 색소 침착 저해 효과를 보이고, 피부내에서 어떤 부작용도 나타나지 않아, 본 발명의 화합물이 안전하고 효과가 매우 뛰어난 기미나 주근깨 개선 또는 피부 미백제임을 알 수 있다.From the results in Table 2 above, ointments and cosmetics containing the compound of the present invention prepared according to Preparation Example 1-6 showed a whitening effect on at least 10 or more of 20 subjects, in particular a large amount of compounds In the comparative experiments of Preparation Example 1 and Comparative Example 1, 35% showed a marked pigmentation inhibitory effect, and no side effects appeared in the skin, so that the compound of the present invention was safe and very effective in improving blemishes or freckles or skin. It can be seen that it is a whitening agent.
따라서. 본 발명의 신규한 벤조산 유도체 및 이를 함유하는 미백 화장료 조성물은 피부의 멜라닌 색소 생성을 억제하여 피부의 흑화, 기미 등을 방지할 수 있다.therefore. The novel benzoic acid derivatives of the present invention and the whitening cosmetic composition containing the same can prevent the skin blackening, blemishes and the like by inhibiting the production of melanin pigmentation of the skin.
도 1은 본발명의 제1실시예에 따라 제조한 의 NMR챠트.1 is prepared according to the first embodiment of the present invention NMR chart of.
도 2는 본발명의 제2 실시예에 따라 제조한 2 is prepared according to a second embodiment of the present invention
Claims (8)
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JPH0848621A (en) * | 1994-06-01 | 1996-02-20 | Kao Corp | Skin whitening cosmetic |
JPH0977651A (en) * | 1995-09-18 | 1997-03-25 | Kao Corp | Beautifying and whitening cosmetic |
JPH0977718A (en) * | 1995-09-18 | 1997-03-25 | Kao Corp | Production of benzoic acid derivative |
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JPH0848621A (en) * | 1994-06-01 | 1996-02-20 | Kao Corp | Skin whitening cosmetic |
JPH0977651A (en) * | 1995-09-18 | 1997-03-25 | Kao Corp | Beautifying and whitening cosmetic |
JPH0977718A (en) * | 1995-09-18 | 1997-03-25 | Kao Corp | Production of benzoic acid derivative |
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