KR102238695B1 - Skin whitening composition comprising gamma-ray irradiated kaki-tannin oligomer as effective component - Google Patents
Skin whitening composition comprising gamma-ray irradiated kaki-tannin oligomer as effective component Download PDFInfo
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- KR102238695B1 KR102238695B1 KR1020190036768A KR20190036768A KR102238695B1 KR 102238695 B1 KR102238695 B1 KR 102238695B1 KR 1020190036768 A KR1020190036768 A KR 1020190036768A KR 20190036768 A KR20190036768 A KR 20190036768A KR 102238695 B1 KR102238695 B1 KR 102238695B1
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- gamma
- melanin
- tannin
- composition
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- Cosmetics (AREA)
Abstract
본 발명은 감마선 조사된 감탄닌을 유효성분으로 함유하는 피부 미백용 조성물에 관한 것으로, 감으로부터 분리된 감탄닌에 감마선을 조사하여 EP-1, EP-2 및 EP-3의 총 3종의 신규 물질이 생성되는 것을 확인하였으며, EP-1, EP-2 및 EP-3는 감마선이 조사되지 않은 감탄닌에 비해 멜라닌 함량 감소 효과가 우수하였고, 특히 감마선이 조사되지 않은 감탄닌, EP-1 및 EP-2에 비해 EP-3의 멜라닌 함량 감소효과가 현저하여, EP-3의 구조 동정을 통해 EP-3은 팡쳉비스플라반 A(fangchengbisflavan A)인 것으로 확인하였으므로, 감마선 조사된 감탄닌 또는 이로부터 분리된 팡쳉비스플라반 A를 유효성분으로 함유하는 본 발명의 조성물은 피부 미백용 화장품, 멜라닌 색소 과다 침착 질환의 예방 또는 개선용 건강기능식품 조성물 또는 치료제로 유용하게 사용될 수 있다. The present invention relates to a composition for skin whitening containing gamma-irradiated tannin as an active ingredient, and a total of three new types of EP-1, EP-2, and EP-3 by irradiating gamma-rays on gamma-rays isolated from persimmon. It was confirmed that the material was produced, and EP-1, EP-2 and EP-3 had excellent melanin content reduction effects compared to the gamma-rayed gamma-rayed sensation tannin, and in particular, the gamma-rayed sensation tannin, EP-1 and Compared to EP-2, the effect of reducing the melanin content of EP-3 was remarkable, and through the structural identification of EP-3, it was confirmed that EP-3 was fangchengbisflavan A. The composition of the present invention containing Pangchengbisflavan A isolated from the active ingredient can be usefully used as a cosmetic for skin whitening, a health functional food composition for preventing or improving melanin hyperpigmentation disease, or a therapeutic agent.
Description
본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 팡쳉비스플라반 A를 유효성분으로 함유하는 피부 미백용 조성물에 관한 것이다. The present invention relates to a composition for skin whitening comprising gamma-irradiated gamtannin or Pangchengbisflavan A isolated therefrom as an active ingredient.
고대부터 희고 밝은 피부는 아름다움뿐만 아니라 건강과 명성의 상징으로 인식해 왔다. 표피 가장 아래 기저층의 멜라닌 세포는 피부의 다양한 자극 요인에 의해 멜라닌을 만들어 위층으로 보내게 되는데, 이 멜라닌이 각질층에 도달하면 피부가 검게 보인다. 멜라닌 형성에 관여하는 요인으로는 난포 호르몬, 황체 호르몬, 색소 세포 자극 호르몬, 햇빛의 자외선, 스트레스 그리고 유전 등이 있다.Since ancient times, white and bright skin has been recognized as a symbol of not only beauty but also health and reputation. The melanocytes in the basement layer at the bottom of the epidermis make melanin by various stimulating factors in the skin and send it to the upper layer. When this melanin reaches the stratum corneum, the skin looks black. Factors involved in melanin formation include follicle hormone, progesterone, pigment cell stimulating hormone, ultraviolet rays from sunlight, stress, and heredity.
불필요해진 멜라닌 색소를 재빨리 배출해서 그 사람이 지니고 있는 본래 피부의 투명함을 되찾는 일을 피부 미백이라 한다. 식품의약품안전청에 닥나무 추출물, 알부틴, 에틸아스코빌에텔, 유용성 감초 추출물, 아스코빌글루코사이드, 나이아신아마이드, 알파-비사볼올 및 아스코빌테트라이소팔미테이트가 미백 성분으로 등록되어 있으며, 이와 같은 물질을 이용해 로션이나 액제, 크림, 마스크팩 등으로 만드는 것이 미백화장품이다.Skin whitening is the quick release of unnecessary melanin pigments and regaining the clarity of the person's original skin. Paper mulberry extract, arbutin, ethyl ascorbyl ether, oil-soluble licorice extract, ascorbyl glucoside, niacinamide, alpha-bisabolol and ascorbyl tetraisopalmitate are registered as whitening ingredients in the Food and Drug Administration. It is a whitening cosmetic that is made with a liquid or liquid, a cream, or a mask pack.
닥나무 추출물, 알부틴, 알파-비사볼올 및 유용성 감초 추출물은 멜라닌을 만드는데 관련된 효소인 티로시나아제가 활성화되는 것을 억제하고, 아스코빌글루코사이드, 에틸아스코빌에텔 및 아스코빌테트라이소팔미테이트는 티로시나아제 효소에 자극받은 티로신이 산화되는 것을 억제하며, 나이아신아마이드는 이미 생성된 멜라닌이 멜라노사이트에서 각질형성세포로 넘어가는 단계를 억제하여 멜라닌이 실제 피부 세포에 들어가는 마지막 단계를 막는다.Black oak extract, arbutin, alpha-bisabolol and oil-soluble licorice extract inhibit the activation of tyrosinase, an enzyme involved in making melanin, and ascorbyl glucoside, ethyl ascorbyl ether, and ascorbyl tetraisopalmitate are tyrosinase enzymes. Inhibits the oxidation of tyrosine stimulated by the body, and niacinamide prevents the last step in which melanin actually enters skin cells by inhibiting the transition of already produced melanin from melanocytes to keratinocytes.
미용이 아닌 의료 목적으로 사용되는 물질의 대표는 의약품으로 처방되는 하이드로퀴논이다. 하이드로퀴논은 주로 피부 연고로 사용된다. 한국에서 이 물질이 4% 이상 함유된 연고를 구입하려면 반드시 의사의 처방이 있어야 하며, 2% 연고는 처방전 없이도 약국에서 구입할 수 있다. 의료 목적으로 사용되는 하이드로퀴논 연고는 미백화장품과는 다르게 멜라닌이 있는 피부 세포를 직접 파괴해 새로운 피부 세포가 자라도록 돕는다.The representative of a substance used for medical purposes other than cosmetic is hydroquinone, which is prescribed as a medicine. Hydroquinone is mainly used as a skin ointment. To purchase an ointment containing more than 4% of this substance in Korea, you must have a doctor's prescription, and 2% ointment can be purchased at a pharmacy without a prescription. Unlike whitening cosmetics, hydroquinone ointment used for medical purposes directly destroys skin cells containing melanin, helping new skin cells grow.
하지만, 상기 물질들은 비교적 높은 농도에서만 티로시나아제 활성 저해 효과가 나타나거나, 안정성이 낮아 효과가 오래 지속되지 못하는 등 제품의 적용 범위가 좁다는 문제점이 있으며, 하이드로퀴논은 피부자극 및 안정성 문제로 인하여 화장료에서의 사용이 제한되고 있다. However, the above substances have a problem that the application range of the product is narrow, such as the effect of inhibiting tyrosinase activity appearing only at a relatively high concentration, or the effect is not long-lasting due to low stability, and hydroquinone is due to skin irritation and stability problems. Its use in cosmetics is limited.
한편, 감의 탄닌은 품종에 관계없이 미숙과에서는 수용성 탄닌으로 존재하며 떫은맛을 낸다. 감이 성숙도가 높아져서 감의 당도가 증가함에 따라 수용성 탄닌 함량은 점차 감소하며 단감의 경우 나뭇가지에 달린 채로 탈삽된다. 탄닌(tannin)은 카키 탄닌(Kaki tannin) 또는 시부올(shibuol)이라 불리는 카테킨(catechin)류로 구성된 축합형 탄닌으로 분류된다. 한편, 감으로부터 얻은 탄닌은 소취(消臭), 통풍예방 효과, 항균작용과 같은 효과가 있음이 알려지고 있다. On the other hand, tannins in persimmons exist as water-soluble tannins in immature fruits regardless of the variety and give off astringent taste. As the persimmon maturity increases and the sugar content of the persimmon increases, the water-soluble tannin content gradually decreases, and the sweet persimmon is removed while hanging on a branch. Tannins are classified as condensed tannins composed of catechins called kaki tannin or shibuol. On the other hand, tannins obtained from persimmon are known to have effects such as deodorization, gout prevention, and antibacterial effects.
한편, 방사선조사 기술(Radiation Technology)은 감마선, 전자선, X-선 등의 방사능 물질이나 방사선 발생장치에서 나오는 에너지 즉, 이온화된 방사선 에너지를 0.01kGy~200kGy의 조사선량으로 조사하는 것으로, 최근에는 이 방사선조사기술을 적용하여 유효성분의 추출율 및 유효성분의 구조 변환에 따른 생리 활성 증진으로 인한 고부가가치 생물 소재 개발에 관한 연구가 진행 중에 있으며, 방사선 조사에 의해 특정 물질의 활성 증가, 특정 물질의 구조 변화 또는 함량을 증가시키는 연구도 보고되고 있으나, 방사선 조사에 따른 감탄닌의 구조 변환 연구에 관해서는 많은 연구가 진행되지 않고 있다. On the other hand, radiation technology is to irradiate radioactive materials such as gamma rays, electron beams, and X-rays, or energy from a radiation generating device, that is, ionized radiation energy at an irradiation dose of 0.01 kGy to 200 kGy. Research on the development of high-value-added biological materials by increasing the physiological activity through the application of radiation irradiation technology and the extraction rate of active ingredients and structure transformation of the active ingredients is in progress. Increased activity of specific substances and structure of specific substances by irradiation Studies to change or increase the content have also been reported, but many studies have not been conducted on the study of structural transformation of gamtannin by irradiation.
한편, 피부 미백과 관련된 선행기술로는 한국등록특허 제1931154호에 루테올린에 방사선을 조사하여 피부 미백 활성을 향상시키는 방법 및 루테올린의 방사선 조사 산물을 유효성분으로 포함하는 피부 미백용 조성물이 개시되어 있고, 한국등록특허 제1313178호에 황칠나무 추출물로부터 분리된 페놀성 화합물을 함유하는 피부 미백 조성물이 개시되어 있지만, 본 발명의 감마선 조사된 감탄닌 또는 이로부터 분리된 팡쳉비스플라반 A를 유효성분으로 함유하는 피부 미백용 조성물에 관해 개시된 바 없다. On the other hand, as a prior art related to skin whitening, a method for improving skin whitening activity by irradiating luteolin with radiation in Korean Patent No. 1931154 and a composition for skin whitening comprising the irradiation product of luteolin as an active ingredient are disclosed. In addition, Korean Patent No. 1313178 discloses a skin whitening composition containing a phenolic compound isolated from Hwangchil tree extract, but the gamma-irradiated gamma-irradiated tannin of the present invention or Pangchengbisflavan A isolated therefrom is effective. There is no disclosure regarding a composition for skin whitening containing as an ingredient.
본 발명은 상기와 같은 요구에 의해 도출된 것으로, 감마선 조사된 감탄닌 또는 이로부터 분리된 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 피부 미백용 조성물을 제공하고, 상기 감마선 조사된 감탄닌 또는 이로부터 분리된 팡쳉비스플라반 A(fangchengbisflavan A)가 감마선이 조사되지 않은 감탄닌에 비해 멜라닌 생성을 억제하는 효과가 우수하다는 것을 확인함으로써, 본 발명을 완성하였다. The present invention is derived from the above requirements, and provides a composition for skin whitening containing gamma-irradiated gamtannin or fangchengbisflavan A isolated therefrom as an active ingredient, and the gamma-ray irradiated The present invention was completed by confirming that gamtannin or fangchengbisflavan A isolated therefrom has an excellent effect of inhibiting melanin production as compared to gamma-ray irradiated gamtannin.
상기 과제를 해결하기 위하여, 본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 하기 화학식 1의 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 피부 미백용 화장료 조성물을 제공한다.In order to solve the above problems, the present invention provides a cosmetic composition for skin whitening containing gamma-irradiated gamtannin or fangchengbisflavan A of the following formula (1) isolated therefrom as an active ingredient.
[화학식 1][Formula 1]
또한, 본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 상기 화학식 1의 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다. In addition, the present invention provides a health functional food composition for preventing or improving melanin hyperpigmentation diseases containing gamma-irradiated gamtannin or fangchengbisflavan A of Formula 1 isolated therefrom as an active ingredient. do.
또한, 본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 상기 화학식 1의 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 치료용 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating melanin hyperpigmentation disorders containing gamma-irradiated gamtannin or fangchengbisflavan A of Formula 1 isolated therefrom as an active ingredient.
본 발명은 감마선 조사된 감탄닌을 유효성분으로 함유하는 피부 미백용 조성물에 관한 것으로, 감으로부터 분리된 감탄닌에 감마선을 조사하여 EP-1, EP-2 및 EP-3의 총 3종의 신규 물질이 생성되는 것을 확인하였으며, EP-1, EP-2 및 EP-3는 감마선이 조사되지 않은 감탄닌에 비해 멜라닌 함량 감소 효과가 우수하였고, 특히 감마선이 조사되지 않은 감탄닌, EP-1 및 EP-2에 비해 EP-3의 멜라닌 함량 감소효과가 현저하였고, 이의 구조 동정을 통해 EP-3은 팡쳉비스플라반 A(fangchengbisflavan A)인 것으로 확인하였다. The present invention relates to a composition for skin whitening containing gamma-irradiated tannin as an active ingredient, and a total of three new types of EP-1, EP-2, and EP-3 by irradiating gamma-rays on gamma-rays isolated from persimmon. It was confirmed that the material was produced, and EP-1, EP-2 and EP-3 had excellent melanin content reduction effects compared to the gamma-rayed gamma-rayed sensation tannin, and in particular, the gamma-rayed sensation tannin, EP-1 and Compared to EP-2, the effect of reducing the melanin content of EP-3 was remarkable, and it was confirmed that EP-3 was fangchengbisflavan A through structural identification.
도 1은 감으로부터 분리된 감탄닌에 감마선을 조사하기 전(A), 40kGy의 감마선을 조사한 후(B) HPLC 결과이다.
도 2는 감마선을 조사하여 신규 생성된 감탄닌 3종(EP-1, EP-2 및 EP-3) 및 감마선을 조사하지 않은 감탄닌의 멜라닌 생성 억제효과를 확인한 결과이다. α-MSH는 멜라닌 생성 유도물질이고, 알부틴은 양성대조군이다.
도 3은 감마선을 조사하여 신규 생성된 감탄닌 EP-3의 티로시나아제(tyrosinase), TRP-1(Tyrosinase-related protein 1) 및 TRP-2(Tyrosinase-related protein 2)의 유전자 발현을 확인한 결과이다.
도 4는 감마선을 조사하여 신규 생성된 감탄닌 EP-3의 티로시나아제(tyrosinase), MITF(melanogenesis associated transcription factor), TRP-1(tyrosinase-related protein 1) 및 TRP-2(tyrosinase-related protein 2)의 단백질 발현을 확인한 결과이다.
도 5는 감마선을 조사하여 신규 생성된 감탄닌 EP-3의 ERK(extracellular signal-regulated kinase) 1/2 단백질 활성화 정도를 확인한 결과이다. 1 is an HPLC result before (A) and after (B) gamma ray irradiation of 40 kGy of gamma ray on gamma ray isolated from persimmon.
FIG. 2 is a result of confirming the melanin production inhibitory effect of three gamma-ray irradiated sensation tannins (EP-1, EP-2 and EP-3) and gamma-rayed sensation tannins. α-MSH is a melanin production inducer, and arbutin is a positive control.
3 is a result of confirming gene expression of tyrosinase, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2) of newly generated gamtannin EP-3 by irradiation with gamma rays to be.
Figure 4 is a tyrosinase (tyrosinase), MITF (melanogenesis associated transcription factor), TRP-1 (tyrosinase-related protein 1) and TRP-2 (tyrosinase-related protein) newly generated by irradiation with gamma rays. This is the result of confirming the protein expression of 2).
5 is a result of confirming the degree of activation of ERK (extracellular signal-regulated kinase) 1/2 protein of newly generated gamtannin EP-3 by irradiation with gamma rays.
본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 하기 화학식 1의 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 피부 미백용 화장료 조성물에 관한 것이다. The present invention relates to a cosmetic composition for skin whitening comprising gamma-irradiated gamtannin or fangchengbisflavan A of the following formula (1) isolated therefrom as an active ingredient.
[화학식 1][Formula 1]
본 발명의 감탄닌은 감에 함유되어 떫은맛을 내는 성분의 총칭으로, 폴리페놀을 기본구조로 한다. 감탄닌은 감의 생합성 조건에 따라 카테킨(cathechin)의 결합 방식과 결합수에 따라 중합도가 달라진다. Gamtannin of the present invention is a generic term for a component that is contained in persimmon to give off astringent taste, and has a basic structure of polyphenol. The degree of polymerization of gamtannin varies depending on the binding method and number of catechins depending on the biosynthesis conditions of the persimmon.
상기 감탄닌은 The exclamatory tannin is
1) 감에 물을 첨가하여 열수 추출한 후 필터한 다음 농축하는 단계;1) adding water to persimmon, extracting hot water, filtering, and then concentrating;
2) 상기 단계 1)의 농축물을 n-헥산(n-hexane), 에틸아세테이트(EtOAc), n-부탄올(n-BuOH) 및 물을 이용하여 순차적으로 분획하는 단계; 및2) sequentially fractionating the concentrate of step 1) using n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and water; And
3) 상기 단계 2)에서 획득한 물 분획물을 농축하는 단계;를 포함하여 제조될 수 있지만, 이에 한정하는 것은 아니다. 3) concentrating the water fraction obtained in step 2), but is not limited thereto.
본 발명의 물 분획물로부터 획득한 감탄닌은 중합체(polymer) 형태를 가진다. 중합체는 동일한 화학구조의 단위가 여러개 반복한 구조를 갖는 고분자 물질이다.The tannin obtained from the water fraction of the present invention has a polymer form. A polymer is a polymer material having a structure in which several units of the same chemical structure are repeated.
본 발명의 일 구현 예에서, 상기 감마선은 5~50kGy의 선량으로 조사할 수 있고, 바람직하게는 10~40kGy의 선량으로 조사할 수 있으며, 더 바람직하게는 40kGy의 선량을 조사하는 것이지만, 이에 제한되는 것은 아니다. In one embodiment of the present invention, the gamma ray may be irradiated at a dose of 5 to 50 kGy, preferably at a dose of 10 to 40 kGy, more preferably a dose of 40 kGy, but limited thereto. It does not become.
본 발명에서 피부 미백효과란, 자외선 노출, 호르몬 밸런스의 변화, 유전적 프로그램 등의 각종 요인에 의해 발생하는 거뭇한 피부나 기미, 주근깨, 다크서클을 개선 또는 방지하는 효과, 피부를 투명감 있는 아름다운 것으로 하는, 혹은 투명감 있는 아름다운 피부를 유지하는 효과, 피부의 칙칙함을 경감하여 윤기ㆍ팽팽함을 증가시키는 효과 등을 의도하고 있다. 일반적으로, 거뭇한 피부나 기미, 주근깨, 다크서클은 자외선에 의한 자극이나 호르몬 밸런스의 변화 등에 의해 멜라노사이트(melanocyte)가 자극되고, 이로 인해 생합성된 멜라닌 색소가 피부에 침착하여 발생한다고 알려져 있다. 따라서, 멜라닌의 생성을 억제할 수 있다면, 거뭇한 피부나 기미, 주근깨, 다크서클을 예방ㆍ개선하는 것이 가능하다.In the present invention, the skin whitening effect refers to the effect of improving or preventing dark skin, spots, freckles, dark circles caused by various factors such as exposure to ultraviolet rays, changes in hormone balance, and genetic programs, and beautiful skin with a sense of transparency. It is intended to reduce the dullness of the skin and increase the glossiness and tension by maintaining the beautiful skin with a sense of transparency or clarity. In general, it is known that dark skin, blemishes, freckles, and dark circles are stimulated by ultraviolet rays or a change in hormonal balance, which stimulates melanocytes, resulting in the deposition of biosynthesized melanin pigments on the skin. Therefore, if the production of melanin can be suppressed, it is possible to prevent and improve dark skin, spots, freckles, and dark circles.
본 발명의 일 구현 예에 따른 화장료 조성물에 있어서, 상기 화장료 조성물은 멜라닌 생합성을 억제할 수 있지만, 이에 제한되지 않는다. In the cosmetic composition according to an embodiment of the present invention, the cosmetic composition may inhibit melanin biosynthesis, but is not limited thereto.
본 발명의 일 구현 예에 따른 화장료 조성물에 있어서, 상기 피부 미백용 화장료 조성물은 스킨, 스킨 소프트너, 스킨 토너, 로션, 밀크로션, 모이스쳐로션, 영양로션, 마사지크림, 영양크림, 아이크림, 모이스쳐크림, 핸드크림, 에센스, 영양에센스, 팩, 클렌징폼, 클렌징워터, 클렌징크림, 바디로션, 바디클렌져, 비누 및 파우더 중에서 선택된 어느 하나의 제형을 가질 수 있으나, 이에 제한되지 않는다. 이들 각 제형으로 이루어진 화장료 조성물은 그 제형의 제제화에 필요하고 적절한 각종의 기제와 첨가물을 함유할 수 있으며, 이들 성분의 종류와 양은 당업자에 의해 용이하게 선정될 수 있다. In the cosmetic composition according to an embodiment of the present invention, the cosmetic composition for skin whitening is a skin, a skin softener, a skin toner, a lotion, a milk lotion, a moisture lotion, a nutrition lotion, a massage cream, a nutrition cream, an eye cream, a moisturizer. Cream, hand cream, essence, nutritional essence, pack, cleansing foam, cleansing water, cleansing cream, body lotion, body cleanser, soap, and powder may have any one formulation selected from, but is not limited thereto. The cosmetic composition composed of each of these formulations may contain various bases and additives necessary and appropriate for the formulation of the formulation, and the types and amounts of these components can be easily selected by those skilled in the art.
본 발명의 화장료 조성물은 유효성분 이외에 추가로 동일 또는 유사한 기능을 나타내는 피부 미백 활성 성분을 1종 이상 함유할 수 있다. 피부 미백 활성 성분으로는 코지산 및 이의 유도체, 알부틴, 아스코르브산 및 이의 유도체, 하이드로퀴논 및 이의 유도체, 레조르시놀, 사이클로알카논, 메틸렌디옥시페닐 알칸올, 2,7-디니트로인다졸 또는 덩굴귤 추출물, 쌀 추출물, 감초 추출물과 같은 식물 추출물 등이 있으나, 이에 제한되는 것은 아니다.The cosmetic composition of the present invention may further contain one or more skin whitening active ingredients exhibiting the same or similar function in addition to the active ingredient. Skin whitening active ingredients include kojic acid and its derivatives, arbutin, ascorbic acid and its derivatives, hydroquinone and its derivatives, resorcinol, cycloalkanone, methylenedioxyphenyl alkanol, 2,7-dinitroindazole or There are plant extracts such as vine tangerine extract, rice extract, and licorice extract, but are not limited thereto.
본 발명의 화장료 조성물의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물섬유, 식물섬유, 왁스, 파라핀, 전분, 트라가칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the cosmetic composition of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, or zinc oxide as carrier components Etc. can be used.
본 발명의 화장료 조성물의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판-부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the cosmetic composition of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Propellants such as carbon, propane-butane or dimethyl ether.
본 발명의 화장료 조성물의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용매화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the cosmetic composition 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 aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.
본 발명의 화장료 조성물의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.When the formulation of the cosmetic composition of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, and the like may be used.
본 발명의 화장료 조성물의 제형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르설페이트, 설포숙신산 모노에스테르, 아세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 리놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the cosmetic composition of the present invention is a surfactant containing cleansing, as a carrier component, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, acetionate, imidazolinium derivative, methyltaurate, sarcosinate , Fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty diethanolamide, vegetable oil, linoline derivative or ethoxylated glycerol fatty acid ester, and the like may be used.
본 발명의 화장료 조성물은 형광물질, 살진균제, 굴수성 유발물질, 보습제, 방향제, 방향제 담체, 단백질, 용해화제, 당 유도체, 일광차단제, 비타민, 식물 추출물 등을 포함하는 부형제를 추가로 함유할 수 있다.The cosmetic composition of the present invention may further contain excipients including fluorescent substances, fungicides, hydrophobic substances, moisturizers, fragrances, fragrance carriers, proteins, solubilizers, sugar derivatives, sunscreen agents, vitamins, plant extracts, etc. .
또한, 본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 하기 화학식 1의 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 개선용 건강기능식품 조성물에 관한 것이다. In addition, the present invention relates to a health functional food composition for preventing or improving melanin hyperpigmentation disease containing gamma-irradiated gamtannin or fangchengbisflavan A of the following formula (1) isolated therefrom as an active ingredient. will be.
[화학식 1][Formula 1]
본 명세서에서 사용되는 용어 "멜라닌 색소 과다 침착(hyperpigmentation)"은 피부 또는 손발톱의 특정 부위에서 멜라닌의 과도한 증가에 의해 다른 부위에 비해 검게 또는 어둡게 되는 것을 의미한다. 상기 멜라닌 색소 과다 침착 질환은 주근깨, 노인성 반점, 간반, 기미, 갈색 또는 흑점, 일광 색소반, 푸른흑피증(cyanic melasma), 약물 사용 후의 과다 색소 침착; 찰상, 화상 또는 피부염으로 인한 염증 후 과다 색소 침착; 또는 임신성 갈색반(gravidic chloasma) 등을 포함하나 이에 한정되지 않는다.As used herein, the term "hyperpigmentation" refers to the darkening or darkening of a specific area of the skin or nail compared to other areas due to an excessive increase in melanin. The melanin hyperpigmentation disease includes freckles, senile spots, liver spots, melasma, brown or dark spots, sun pigment spots, cyanic melasma, hyperpigmentation after drug use; Hyperpigmentation after inflammation from scratches, burns or dermatitis; Or gestational brown spots (gravidic chloasma), but are not limited thereto.
본 발명의 건강기능식품 조성물을 식품첨가물로 사용하는 경우, 상기 건강기능식품 조성물을 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 양은 그의 사용 목적(예방 또는 개선)에 따라 적절하게 사용될 수 있다. 일반적으로, 식품 또는 음료의 제조시 본 발명의 건강기능식품 조성물은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나 건강을 목적으로 하는 장기간의 섭취인 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로 사용될 수 있다.When using the health functional food composition of the present invention as a food additive, the health functional food composition may be added as it is or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method. The amount of the active ingredient can be appropriately used depending on the purpose of use (prevention or improvement). In general, when preparing food or beverage, the health functional food composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less based on the raw material. However, in the case of long-term intake for the purpose of health, the amount may be less than the above range, and there is no problem in terms of safety, so the active ingredient may be used in an amount above the above range.
상기 건강기능식품의 종류에 특별한 제한은 없다. 상기 건강기능식품 조성물을 첨가할 수 있는 식품의 예로는 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the types of the health functional food. Examples of foods to which the health functional food composition can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea There are drinks, alcoholic beverages, and vitamin complexes, and all health foods in the usual sense are included.
또한, 본 발명의 건강기능식품 조성물은 식품, 특히 기능성 식품으로 제조될 수 있다. 본 발명의 기능성 식품은 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다. 예컨대, 드링크제로 제조되는 경우에는 유효성분 이외에 천연 탄수화물 또는 향미제를 추가 성분으로서 포함할 수 있다. 상기 천연 탄수화물은 모노사카라이드(예컨대, 글루코오스, 프럭토오스 등), 디사카라이드(예컨대, 말토스, 수크로오스 등), 올리고당, 폴리사카라이드(예컨대, 덱스트린, 시클로덱스트린 등) 또는 당알코올(예컨대, 자일리톨, 소르비톨, 에리쓰리톨 등)인 것이 바람직하다. 상기 향미제는 천연 향미제(예컨대, 타우마틴, 스테비아 추출물 등)와 합성 향미제(예컨대, 사카린, 아스파르탐 등)를 이용할 수 있다.In addition, the health functional food composition of the present invention may be prepared as a food, particularly a functional food. Functional foods of the present invention include ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, when prepared as a drink, a natural carbohydrate or flavoring agent may be included as an additional ingredient in addition to the active ingredient. The natural carbohydrates are monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrins, cyclodextrins, etc.) or sugar alcohols (e.g. , Xylitol, sorbitol, erythritol, etc.). As the flavoring agent, natural flavoring agents (eg, taumatin, stevia extract, etc.) and synthetic flavoring agents (eg, saccharin, aspartame, etc.) may be used.
상기 건강기능식품 조성물 이외에 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 더 함유할 수 있다. 이러한 상기 첨가되는 성분의 비율은 크게 중요하진 않지만 본 발명의 건강기능식품 조성물 100 중량부에 대하여, 0.01 내지 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above health functional food composition, various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonic acid It may further contain a carbonation agent used in beverages. Although the ratio of the ingredients to be added is not very important, it is generally selected from 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.
또한, 본 발명은 감마선 조사된 감탄닌 또는 이로부터 분리된 하기 화학식 1의 팡쳉비스플라반 A(fangchengbisflavan A)를 유효성분으로 함유하는 멜라닌 색소 과다 침착 질환의 예방 또는 치료용 약학 조성물에 관한 것이다. In addition, the present invention relates to a pharmaceutical composition for preventing or treating melanin hyperpigmentation disorders containing gamma-irradiated gamtannin or fangchengbisflavan A of the following formula (1) isolated therefrom as an active ingredient.
[화학식 1][Formula 1]
본 발명의 약학조성물은 유효성분 이외에 약학적으로 허용되는 담체를 포함할 수 있으며, 이러한 담체는 제제 시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient, and such carriers are commonly used in formulation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, Calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and minerals It includes, but is not limited to, oil and the like. The pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like in addition to the above components.
본 발명에 따른 약학조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. The appropriate dosage of the pharmaceutical composition according to the present invention is prescribed in various ways depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient. Can be.
본 발명의 약학조성물은 경구 또는 비경구로 투여할 수 있으며, 비경구 투여의 경우, 피부에 국소적으로 도포, 정맥 내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있다. 본 발명의 약학조성물이 멜라닌 색소 과다 침착 질환의 치료 또는 예방을 위해 적용되는 점을 감안하면, 피부에 국소적으로 도포되어 이루어지는 것이 바람직하다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by topical application to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, and the like. In view of the fact that the pharmaceutical composition of the present invention is applied for the treatment or prevention of melanin hyperpigmentation disease, it is preferably applied topically to the skin.
본 발명의 조성물에 포함되는 유효성분의 농도는 치료 목적, 환자의 상태, 필요기간 등을 고려하여 결정할 수 있으며, 특정 범위의 농도로 한정되지 않는다.The concentration of the active ingredient contained in the composition of the present invention may be determined in consideration of the purpose of treatment, the condition of the patient, the required period, etc., and is not limited to a specific range of concentration.
본 발명의 약학조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약학적으로 허용되는 담체 또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 주사제, 크림, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 및 카타플라스마제 중에서 선택된 어느 하나의 제형으로 제조될 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.
The pharmaceutical composition of the present invention is prepared in a unit dosage form by formulating using a pharmaceutically acceptable carrier or excipient according to a method that can be easily carried out by a person having ordinary knowledge in the technical field to which the present invention belongs, or It can be manufactured by enclosing it in a dose container. At this time, the formulation may be prepared in any one formulation selected from injections, creams, patches, sprays, ointments, warning agents, lotions, liniment, pasta and cataplasma, and may additionally include a dispersant or a stabilizer. have.
이하, 제조예 및 실시예를 이용하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 제조예 및 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로 본 발명의 범위가 이들에 의해 제한되지 않는다는 것은 당해 기술분야에서 통상의 지식을 가진 자에게 있어 자명한 것이다.
Hereinafter, the present invention will be described in more detail using Preparation Examples and Examples. These preparation examples and examples are only for describing the present invention in more detail, and it is obvious to those of ordinary skill in the art that the scope of the present invention is not limited thereto.
제조예Manufacturing example 1. One. 감탄닌의Exclamatory 제조 Produce
2017년 10월 경상북도 청도군 각북면 풀빛농원에서 수확한 신선한 감 3.0kg을 열수 추출하여 필터한 후 농축하였다. 그 후 상기 농축물을 n-헥산(n-hexane), 에틸아세테이트(EtOAc), n-부탄올(n-BuOH) 및 물을 이용하여 순차적으로 분획한 후, 진공 농축한 다음 각각 23.5g의 n-헥산 분획물, 1.7g의 에틸아세테이트 분획물, 623.0g의 n-부탄올 분획물 및 372.0g의 물 분획물을 획득하였다. In October 2017, 3.0 kg of fresh persimmons harvested at Pulbit Farm, Gakbuk-myeon, Cheongdo-gun, Gyeongsangbuk-do, were extracted with hot water, filtered, and concentrated. Then, the concentrate was sequentially fractionated using n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and water, concentrated in vacuo, and then 23.5 g of n- A hexane fraction, 1.7 g of ethyl acetate fraction, 623.0 g of n-butanol fraction, and 372.0 g of water fraction were obtained.
각각의 분획물 분석 결과, 본 발명의 목표 성분인 감탄닌 폴리머는 물 분획물에 대량 존재하는 것으로 확인하여, 이후 물 분획물의 감탄닌 폴리머에 감마선을 조사하였다.
As a result of analyzing each fraction, it was confirmed that a large amount of the gamtannin polymer, which is the target component of the present invention, is present in the water fraction, and then gamma rays were irradiated on the gamma-rays on the gamma-ray polymer of the water fraction.
제조예Manufacturing example 2. 감마선이 조사된 2. Gamma irradiated 감탄닌의Exclamatory 제조 Produce
상기 제조예 1에서 획득한 감탄닌 폴리머에 감마선을 조사하였다. 감탄닌 폴리머 1.5g에 20%(v/v) 메탄올을 300mL 첨가한 후 감마선을 10~40kGy 선량으로 조사하여 조사 산물을 획득하였다. Gamma rays were irradiated on the sensation tannin polymer obtained in Preparation Example 1. After adding 300 mL of 20% (v/v) methanol to 1.5 g of the tannin polymer, gamma rays were irradiated at a dose of 10 to 40 kGy to obtain an irradiated product.
감마선 조사에 따른 감탄닌의 변화 양상은 역상 고성능액체크로마토그래피(HPLC, high-performance liquid chromatography)를 통해 모니터링하였다. Changes in gamtannin according to gamma irradiation were monitored through high-performance liquid chromatography (HPLC).
그 결과, 도 1에 개시된 바와 같이 감탄닌 폴리머에 감마선을 조사하였을 경우, 감마선이 조사되지 않은 감탄닌에서는 검출되지 않던 피크가 검출되었으며, 검출 순서에 따라 각각의 피크를 EP-1, EP-2 및 EP-3로 명명하였다. As a result, when gamma rays were irradiated to the tannin polymer as disclosed in FIG. 1, peaks that were not detected in the tannins to which the gamma rays were not irradiated were detected, and each peak was EP-1 and EP-2 according to the detection order. And EP-3.
이후, YMC 겔 ODS AQ 120-50S(1.0cm i.d.X43cm)를 활용한 컬럼 크로마토그래피를 수행하였다. 10%(v/v) 메탄올을 이용하여 용출한 용출액의 51~62번째 분획에서 EP-1을 분리하였고, 15%(v/v) 메탄올을 이용하여 용출한 용출액의 77~83번째 분획에서 EP-2를 분리하였고, 25%(v/v) 메탄올을 이용하여 용출한 용출액의 129~145번째 분획에서 EP-3을 분리하였다.Then, column chromatography was performed using YMC gel ODS AQ 120-50S (1.0cm i.d.X43cm). EP-1 was isolated from the 51st to 62nd fractions of the eluate eluted with 10% (v/v) methanol, and EP-1 from the 77th to 83rd fraction of the eluate eluted with 15% (v/v) methanol. -2 was separated, and EP-3 was separated from the 129th to 145th fractions of the eluate eluted with 25% (v/v) methanol.
각각의 분리 물질은 HPLC로 보유시간 및 순도를 확인하여 EP-1, EP-2 및 EP-3이 감마선 조사에 의해 신규 생성된 화합물이라는 것을 확인하였다. 이동상으로 H2O:MeCN이 99:1의 부피비로 혼합된 용액을 사용하였고, 유량(flow rate)은 1.0mL/분으로 245nm에서 분석하였다. Retention time and purity of each separated material were confirmed by HPLC, and it was confirmed that EP-1, EP-2, and EP-3 were newly formed compounds by gamma irradiation. A solution in which H 2 O:MeCN was mixed in a volume ratio of 99:1 was used as the mobile phase, and the flow rate was analyzed at 245 nm at 1.0 mL/min.
감마선 선량별 EP-1, EP-2 및 EP-3 생성 함량은 하기 표 1에 개시된 바와 같다. The amounts of EP-1, EP-2, and EP-3 produced by gamma-ray dose are as disclosed in Table 1 below.
((
minmin
))
실시예Example 1. One. 감탄닌에To admiration 감마선을 조사한 후 분리된 물질( The material separated after irradiation with gamma rays ( EPEP -1, -One, EPEP -2 및 -2 and EPEP -- 3)의3) of 미백 효과 확인 Check the whitening effect
1) 분리 물질의 멜라닌 합성 억제효과1) Melanin synthesis inhibitory effect of isolated substances
멜라닌 생성 세포 및 흑색종 세포는 α-MSH 자극에 의해 멜라닌 생성이 촉진된다. B16/F10 흑색종 세포에 α-MSH, 감마선이 조사되지 않은 감탄닌(kaki-tannin) 및 감탄닌에 감마선을 조사한 후 분리된 물질인 EP-1, EP-2 및 EP-3를 각각 처리하여 감탄닌, EP-1, EP-2 및 EP-3의 멜라닌 합성 저해효과를 확인하였다. 감탄닌, EP-1, EP-2 및 EP-3는 40㎍/mL 농도에서 세포 독성을 갖지 않는다는 것을 확인한 후 각 물질을 10~30㎍/mL의 농도로 처리하였다. Melanin-producing cells and melanoma cells are promoted to produce melanin by α-MSH stimulation. B16/F10 melanoma cells were irradiated with α-MSH, gamma irradiated gamma ray, and gamma ray irradiated, and then treated with EP-1, EP-2, and EP-3, respectively. The inhibitory effect of melanin synthesis of gamtannin, EP-1, EP-2 and EP-3 was confirmed. After confirming that gamtannin, EP-1, EP-2 and EP-3 had no cytotoxicity at a concentration of 40 μg/mL, each substance was treated at a concentration of 10 to 30 μg/mL.
그 결과, 도 2에 개시된 바와 같이 감탄닌에 비해 감마선을 조사한 감탄닌으로부터 분리된 EP-1, EP-2 및 EP-3의 멜라닌 함량 감소효과가 우수하였으며, 특히 EP-3의 멜라닌 함량 감소효과가 현저하였다. As a result, as shown in FIG. 2, the effect of reducing the melanin content of EP-1, EP-2, and EP-3 isolated from the gamma-rayed sensation tannin compared to the gamma-rayed sensation tannin was excellent, and in particular, the melanin content reduction effect of EP-3 Was remarkable.
멜라닌 함량 감소효과가 가장 우수한 EP-3의 티로시나아제, TRP-1 및 TRP-2 유전자 발현량을 분석한 결과, 도 3에 개시된 바와 같이 α-MSH 자극에 의해 증가된 각 유전자의 발현이 EP-3를 처리한 경우 현저히 감소되어 있었고, 티로시나아제, MITF, TRP-1 및 TRP-2의 단백질 발현을 확인한 결과, 도 4에 개시된 바와 같이 유전자 발현과 비슷한 패턴으로 EP-3에 의해 단백질 발현이 감소하는 것을 확인할 수 있었다. As a result of analyzing the expression levels of tyrosinase, TRP-1 and TRP-2 genes of EP-3, which has the best melanin content reduction effect, the expression of each gene increased by α-MSH stimulation as disclosed in FIG. 3 was EP When -3 was treated, it was significantly reduced, and as a result of confirming the protein expression of tyrosinase, MITF, TRP-1 and TRP-2, protein expression by EP-3 in a pattern similar to gene expression as disclosed in FIG. 4 It could be confirmed that this decreases.
α-MSH 자극에 의해 증가된 ERK 1/2의 활성화가 EP-3에 의해 억제되는지 확인한 결과, 도 5에 개시된 바와 같이 EP-3 처리시 ERK 1/2의 인산화가 억제되어 EP-3이 ERK 1/2의 억제 활성을 나타낸다는 것을 확인하였다. As a result of confirming whether the activation of
이를 바탕으로 EP-3은 세포내에서 ERK 1/2의 신호전달을 억제함으로써, 티로시나아제 활성을 억제하고, 멜라닌 함성을 억제하는데 관여한다는 것을 확인하였다.
Based on this, it was confirmed that EP-3 is involved in suppressing tyrosinase activity and suppressing melanin by inhibiting the signaling of
실시예Example 2. 2. 감탄닌에To admiration 감마선을 조사한 후 분리된 Separated after irradiation with gamma rays EPEP -3 구조동정-3 structural identification
상기 실시예 1에서 우수한 미백 활성을 나타낸 EP-3의 구조를 동정하였다. In Example 1, the structure of EP-3, which exhibited excellent whitening activity, was identified.
EP-3은 갈색 무결정형의 가루형태로 분리하였으며, 비선광도 측정 결과, [α]20D -137.7°(MeOH)로 측정되었다. FABMS 스펙트럼 측정 결과 positive mode로 m/z 593[M+H]+의 base peak를 확인하여 분자량을 추정하였고, 분자식은 C31H27O12로 확인되었다. UV 최대 흡광도는 281nm로 측정되었으며, 전형적인 flavan-3-ol의 골격이 나타났다. 1H NMR 데이터 해석으로 두 개의 ABX-t타입의 방향족 신호(aromatic signal)가 δH 7.09(1H, d, J=1.8Hz, H-2'), 6.93(1H, d, J=1.2Hz, H-2a'), 6.90(1H, dd, J=8.4, 1.8Hz, H-6'), 6.81(1H, d, J=8.4Hz, H-5'), 6.75(1H, dd, J=7.8, 1.2Hz, H-6a'), 6.73(1H, d, J=7.8Hz, H-5a')로 측정되었으며, 두 개의 방향족의 양성자 신호(aromatic proton signal)가 δH 6.07(1H, s, H-6), 5.98(1H, s, H-8)에서 측정되었다. 또한, 4개의 산화된 메틴 양성자 신호(oxygenated methine proton signal)가 δH 4.99(1H, brs, H-2), 4.73(1H, brs, H-2a), 4.18(1H, m, H-3), 4.11(1H, m, H-3a)로 측정되었으며 메틸렌 양성자 신호(methylene proton signal)가 δH 2.89(1H, dd, J=16.8, 4.8Hz, H-4), 2.79(1H, dd, J=16.2, 4.8, H-4a), 2.78(1H, dd, J=16.2, 3.6, H-4), 2.69(1H, dd, J=16.8, 3.0Hz, H-4a)로 측정되었다. H-2 및 3의 결합 정수는 작은 커플링 상수(small-coupling constant)를 보였으며, 이 신호들은 전형적인 (-)-에피카테킨의 H-2, 3의 2,3-cis 형태(configuration)인 것을 확인하였다. 그 외 추가적으로 메틸렌 가교된 양성자 신호(methylene-bridged proton signal)가 δH 3.78(1H, d, J=15.6Hz, H-CH2), 3.75(1H, d, J=15.6Hz, H-CH2)로 측정되어, (-)-에피카테킨이 메틸렌 가교된(methylene-bridged) 결합으로 이루어진 이량체로 구조를 추정하였다. EP-3 was separated into a brown amorphous powder form, and as a result of measuring the specific rotation, [α] was measured as 20 D -137.7° (MeOH). As a result of FABMS spectrum measurement, the molecular weight was estimated by confirming the base peak of m/z 593[M+H] + in positive mode, and the molecular formula was confirmed as C 31 H 27 O 12. The maximum UV absorbance was measured at 281 nm, and a typical flavan-3-ol skeleton was shown. 1 H NMR data analysis shows that two ABX-t type aromatic signals are δ H 7.09 (1H, d, J =1.8Hz, H-2'), 6.93 (1H, d, J =1.2Hz, H-2a'), 6.90(1H, dd, J =8.4, 1.8Hz, H-6'), 6.81(1H, d, J =8.4Hz, H-5'), 6.75(1H, dd, J = 7.8, 1.2Hz, H-6a'), 6.73 (1H, d, J =7.8Hz, H-5a'), and the two aromatic proton signals were δ H 6.07 (1H, s , H-6), 5.98 (1H, s, H-8). In addition, four oxidized methine proton signals are δ H 4.99 (1H, brs, H-2), 4.73 (1H, brs, H-2a), 4.18 (1H, m, H-3) , 4.11 (1H, m, H-3a) and methylene proton signal of δ H 2.89 (1H, dd, J =16.8, 4.8Hz, H-4), 2.79 (1H, dd, J =16.2, 4.8, H-4a), 2.78 (1H, dd, J =16.2, 3.6, H-4), 2.69 (1H, dd, J =16.8, 3.0Hz, H-4a). The coupling constants of H-2 and 3 showed a small-coupling constant, and these signals were typical of (-)-epicatechin in the 2,3-cis configuration of H-2 and 3. Confirmed. In addition, the methylene-bridged proton signal is δ H 3.78 (1H, d, J =15.6Hz, H-CH 2 ), 3.75 (1H, d, J =15.6Hz, H-CH 2 ), and the (-)-epicatechin was estimated to be a dimer consisting of a methylene-bridged bond.
13C NMR 및 HSQC 스펙트럼 데이터 해석으로 24개의 방향족 탄소 신호(aromatic carbon signal)를 확인하였으며, 4개의 산화된 탄소 신호(oxygenated carbon signal)가 δC 81.4(C-2), 79.8(C-2a), 67.5(C-3), 67.0(C-3a)에서 확인되었으며, 메틸렌 탄소 신호(methylene carbons signal)가 δC 29.6(C-4), 29.3(C-4a)에서 확인되어 (-)-에피카테킨의 골격인 것을 시사하였다. 그 외 양성자(proton)에서 추가적으로 측정되었던 메틸렌 가교 신호(methylene-bridged signal) 역시 δC 17.4(C-CH2)로 확인하였다. 13 C NMR and HSQC spectral data analysis confirmed 24 aromatic carbon signals, and 4 oxygenated carbon signals were δ C 81.4 (C-2), 79.8 (C-2a). , 67.5 (C-3), 67.0 (C-3a), methylene carbons signal was identified at δ C 29.6 (C-4), 29.3 (C-4a), (-)-epicatechin It was suggested that it is the skeleton of. In addition, the methylene-bridged signal, which was additionally measured from the proton, was also confirmed as δ C 17.4 (C-CH 2 ).
Key HMBC 스펙트럼 해석으로 H-2가 C-9, H-2a가 C-9a까지, H-4가 C-5, 9, 10까지 H-4a가 C-5a, 9a, 10a까지 상관관계가 측정되었으며, 메틸렌 가교 양성자(methylene-bridged proton)가 C-7, 8, 9, 6a, 6a, 7a까지 상관관계가 측정되었으며, H-6이 C-5, 7, 8, H-8a가 C-6a, 7a, 9a까지 측정되었다. 그 외 추가적으로 1H-1H COSY 스펙트럼에서 H-2, 3, 4 및 H-2a, 3a, 4a가 서로 상관관계에 있다는 것이 측정되었다. Key HMBC spectrum analysis measures the correlation for H-2 to C-9, H-2a to C-9a, H-4 to C-5, 9, 10, H-4a to C-5a, 9a, 10a Correlation was measured for methylene-bridged protons up to C-7, 8, 9, 6a, 6a, 7a, and H-6 was C-5, 7, 8, and H-8a was C- It was measured up to 6a, 7a, and 9a. In addition, it was determined that H-2, 3, 4 and H-2a, 3a, 4a were correlated with each other in the 1H-1H COSY spectrum.
이상의 결과로 (-)-에피카테킨의 6번 및 8번 위치에서 메틸렌 가교(methylene-bridged)로 연결된 (-)-에피카테킨 이량체로 구조를 동정하였으며, 1D-, 2D NMR의 스펙트럼 해석과 문헌치와 비교한 결과 EP-3은 팡쳉비스플라반 A(fangchengbisflavan A)로 구조를 동정하였다.As a result of the above results, the structure was identified as a (-)-epicatechin dimer connected by methylene-bridged at positions 6 and 8 of (-)-epicatechin. Spectral analysis of 1D- and 2D NMR and comparison with literature values As a result, the structure of EP-3 was identified as fangchengbisflavan A.
Claims (6)
[화학식 1]
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[화학식 1]
[Formula 1]
[화학식 1]
[Formula 1]
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