KR20160056268A - Composition for the inhibition of UV-induced melanogenesis or anti inflammatory comprising extracts or fractions of Psidium guajava L. - Google Patents
Composition for the inhibition of UV-induced melanogenesis or anti inflammatory comprising extracts or fractions of Psidium guajava L. Download PDFInfo
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- KR20160056268A KR20160056268A KR1020150139525A KR20150139525A KR20160056268A KR 20160056268 A KR20160056268 A KR 20160056268A KR 1020150139525 A KR1020150139525 A KR 1020150139525A KR 20150139525 A KR20150139525 A KR 20150139525A KR 20160056268 A KR20160056268 A KR 20160056268A
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- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A—HUMAN NECESSITIES
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- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
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Abstract
본 발명은 구아바, 보다 구체적으로 구아바 잎 (Psidium guajava L.)의 추출물 또는 이의 분획물을 함유하는 피부 미백용 또는 항염증용 조성물에 관한 것이다.
본 발명의 조성물을 이용하면, 일광(日光) 조사 시 피부 멜라닌 세포 멜라닌 형성으로 인한 피부흑화 시 중요한 역할을 담당하는 Orai-1 이온통로를 억제할 뿐만 아니라 티로시나제 활성을 저해할수 있는 효과를 가진다. 또한, Orai-1은 면역활성에 중요한 칼슘이온 통로이므로 이를 효과적으로 억제하면 각종 염증성 질환을 해결할 수 있는 효과를 가진다.
구아바 잎은 현재 식용으로 사용될 만큼 세포독성이 없는 안전한 물질이므로, 자외선에 의한 피부 손상 그리고 기관지천식, 알레르기비염, 아토피피부염 등 염증/면역성 질환 예방 및 치료에 유용하게 사용될 수 있을 것이다.The present invention relates to a skin whitening or anti-inflammatory composition containing guava, more particularly an extract of Guidaba leaf (Psidium guajava L.) or a fraction thereof.
When the composition of the present invention is used, it has an effect of inhibiting tyrosinase activity as well as inhibiting Orai-1 ion channel which plays an important role in skin darkening due to skin melanin cell melanin formation during sunlight irradiation. In addition, Orai-1 is a calcium ion pathway important for immunological activity, and effectively inhibiting it can solve various inflammatory diseases.
Since guava leaves are safe substances that are not cytotoxic enough to be used for edible purposes, they may be useful for the prevention and treatment of inflammatory / immune diseases such as bronchial asthma, allergic rhinitis and atopic dermatitis.
Description
본 발명은 구아바 (Polygonum viscoferum) 추출물 또는 이의 분획물을 유효성분으로 포함하는 피부 미백 또는 항염증용 조성물에 관한 것이다.The present invention relates to a polygonum viscoferum ) extract or a fraction thereof as an active ingredient for skin whitening or anti-inflammation.
멜라닌 세포의 활성에 따른 멜라닌 형성은 크게 두 가지 신호전달 기전을 통해 일어날 수 있다. 첫 번째는 세포 내 cAMP 자극에 의해 일어나는 멜라닌 형성 기전이고 두 번째는 세포내 칼슘 농도 증가에 따른 멜라닌 형성 기전이다.Melanogenesis due to the activity of melanocytes can occur through two signal transduction mechanisms. The first is the mechanism of melanin formation by intracellular cAMP stimulation and the second is the mechanism of melanin formation by increasing intracellular calcium concentration.
두 신호전달 기전이 서로 복잡하게 상호작용을 하기 때문에 서로 완벽히 분리되어 작용하지는 않지만, 멜라닌 형성의 가장 대표적인 기전이라 할 수 있는 멜라닌 형성 자극 호르몬에 의해 일어나는 피부 흑화 기전의 경우 proopiomelanocortin (POMC)/Melanocortin receptors 1 (MC1-R)/cyclicAMP (cAMP) 전달경로를 통하는 것으로 melanocyte stimulating hormone (α-MSH)이나 adrenocorticotropic hormone (ACTH)에 의해 시작된다.In the case of melanocortin-induced melanocortin-induced melanocortin (POMC) / melanocortin receptors (melanocortin receptors), melanocortin receptors 1 (MC1-R) / cyclicAMP (cAMP) pathway, initiated by melanocyte-stimulating hormone (α-MSH) or adrenocorticotropic hormone (ACTH).
반면 외인성 노화에 의한 흑화 즉, 자외선 조사에 의한 멜라닌 형성의 경우, 최근 ISI web of knowledge dermatology 분야 1위 저널인 JOURNAL OF INVESTIGATIVE DERMATOLOGY에 따르면 (2012 May;132(5):1443-51), 자외선이 조사되면 멜라닌 세포가 활성화되어 멜라닌을 형성하는데, 세포 내 칼슘 농도 증가에 의한 멜라닌 형성 기전이 작동한다고 한다. 좀 더 자세히 기술하면 세포내 칼슘 농도 증가를 위해서는 세포 밖에서의 칼슘 유입이 매우 중요한데, 이 논문에 따르면 Orai-1 이온통로를 통한 세포 내 칼슘 유입이 이러한 멜라닌 형성에 중요한 역할을 한다고 한다.On the other hand, according to JOURNAL OF INVESTIGATIVE DERMATOLOGY (2012 May; 132 (5): 1443-51), the first journal in the ISI web of knowledge dermatology, the ultraviolet When examined, melanin cells are activated to form melanin, which is believed to be due to an increase in intracellular calcium concentration. More specifically, the
상기 논문에서 인간 멜라닌 세포를 이용하여 Orai-1 저해제를 처리해 본 결과, 자외선에 의한 멜라닌 형성이 억제된다는 것이 확인되었다. 따라서, 멜라닌 세포 Orai-1 이온통로를 타깃으로 하여, 이를 억제할 수 있는 약물이 개발된다면, 자외선에 의한 피부 흑화 억제제가 개발 될 수 있을 것으로 예상되었다.In the above-mentioned article, it was confirmed that the treatment of Orai-1 inhibitor using human melanocytes inhibited the formation of melanin due to ultraviolet light. Therefore, if a drug capable of inhibiting the melanocyte Orai-1 ion channel is developed, it is expected that an inhibitor of skin blackening by ultraviolet rays can be developed.
최근 여러 화학물질 등에 의한 피부 자극을 줄이기 위해 천연 추출물로부터 얻어진 항산화, 주름완화, 미백 등의 기능을 가진 기능성 피부 외용제(functional cosmetics)에 많은 관심이 집중되고 있다. 천연 재료는 피부에 부작용이 적을 뿐 아니라, 최근 천연 재료를 이용한 피부 외용제에 대한 소비자들의 호응이 높아짐에 따라 피부 외용제 원료로서 개발가치가 한층 커지고 있다.Recently, much attention has been focused on functional cosmetics having functions of antioxidation, wrinkle reduction, whitening, etc., obtained from natural extracts in order to reduce skin irritation caused by various chemical substances and the like. In addition to low adverse effects on the skin, natural materials have recently become increasingly appreciated as a raw material for skin external preparations, as consumers' responses to external preparations using natural materials have increased.
현재 개발되고 있는 광노화 억제에 쓰이는 유효성분들은 화장품 원료로 사용할 수 없거나 매우 불안정하고, 피부로의 전달이 용이하지 않아 특별한 안정화 시스템과 전달체계가 필요하며, 피부주름의 개선효과가 가시적이지 않는 등의 문제점이 있어서 최근 레티노이드(retinoid)를 함유한 피부보호제로 관심이 점차 집중되고 있으며, 현재 레티노이드는 일광으로 축적된 결과인 주름살, 피부의 두꺼워짐, 처짐, 탄력 감소 등의 광노화 현상을 해결하는 수단으로 이용되고 있다. 그러나 레티노이드는 매우 불안정한 화합물로 자외선, 수분, 열, 산소에 민감하여 쉽게 화학적인 변화를 일으키는 문제점이 있어 이를 해결하기 위한 천연물 연구에 집중되고 있는 실정이다.The active ingredients used for suppression of photoaging are not available as cosmetic raw materials, are very unstable, are not easily transferred to the skin, require a special stabilization system and delivery system, and the effect of improving skin wrinkles is not visible Recently, retinoids have been increasingly attracted attention as a skin protective agent containing retinoids. Currently, retinoids are a means for solving photoaging phenomena such as wrinkles, skin thickening, sagging, and elasticity reduction which are accumulated as sunlight . However, retinoids are very unstable compounds, and they are sensitive to ultraviolet rays, moisture, heat, and oxygen, causing chemical changes easily.
한편, 면역세포가 항원 및 항체에 노출이 되면 면역수용체 자극이 일어나 세포 내 phospholipase C (PLC) 활성에 의한 칼슘유리 및 ER 칼슘 고갈에 의해서 지속적인 칼슘유입이 활성화된다. 면역세포 칼슘유입은 2006년 그 분자적 성상이 밝혀진 ORAI-1 & STIM protein complex를 통해 이루어진다. 이 complex를 통한 칼슘유입은 calcineurin-NFAT-IL-2 생성 pathway를 활성화하는데 중요하다고 알려져 있다. ORAI1 이온통로를 통한 칼슘 유입이 없으면 IL-2의 생성이 감소하고, 림프구의 증식과 T세포 매개성 면역 반응이 감소하여 면역결핍 질환이 발생한다. 실제로 사람에 있어 ORAI-1 이온 통로 및 STIM1이 결핍되었을 때 심각한 면역 결핍 질환이 일어난다는 보고가 Nature 및 New England Journal of Medicine에 보고 되었다.On the other hand, when the immune cells are exposed to the antigen and the antibody, the immunoreceptor stimulation occurs and the continuous calcium influx is activated by the calcium glass and ER calcium depletion due to intracellular phospholipase C (PLC) activity. The influx of calcium into the immune cells is accomplished through the ORAI-1 & STIM protein complex whose molecular properties are revealed in 2006. Calcium influx through this complex is known to be important in activating the calcineurin-NFAT-IL-2 production pathway. Without calcium influx through the ORAI1 ion channel, IL-2 production is reduced, lymphocyte proliferation and T cell-mediated immune responses are reduced, resulting in immunodeficiency disease. Indeed, a serious immunodeficiency disease can occur in humans when the ORAI-1 ion channel and STIM1 deficiency are reported in Nature and the New England Journal of Medicine.
현재 임상적으로 적용하고 있는 강력한 면역 억제제인 tacrolimus나 glucocorticoid와 같은 약물의 타깃이 되는 calcineurin이나 mRNA 전사 조절 관련 인자들의 활성은 모두 세포 내 칼슘 농도 증가에 의해 시작되며 이러한 세포 내 칼슘 신호 생성은 세포 밖 칼슘을 세포 내로 직접 운반하는 Orai-STIM complex에 의해 조절이 일어난다. 따라서, 이들 이온 통로를 조절하는 물질을 개발하여 사용한다면 강력한 면역조절 효과를 가질 수 있다.The activity of calcineurin or mRNA transcriptional regulatory factors, which are the targets of drugs such as tacrolimus and glucocorticoid, which are currently clinically applied as powerful immunosuppressants, is initiated by an increase in intracellular calcium concentration, It is regulated by the Orai-STIM complex, which carries calcium directly into the cell. Therefore, if a substance that regulates these ion channels is developed and used, it can have a strong immunoregulatory effect.
따라서, 세포 내 칼슘 신호를 생성하는 Orai-1 이온 통로를 타깃으로 천연물 유래 염증 억제제를 개발한다면 현존하는 치료제보다 훨씬 더 강력한 면역억제 능력을 발휘할 수 있을 것이다.Therefore, if a natural substance-derived inflammation inhibitor is developed targeting the Orai-1 ion channel that produces an intracellular calcium signal, it will be able to exert a much stronger immunosuppressive ability than the existing therapeutic agent.
한편, 구아바는 도금양과(Myrtaceae과) Psidium 속의 미국산 열대성 식물로서, 화분식물은 물론 잎, 나무껍질, 열매 등을 건강식 및 약용으로 이용할 수 있는 약용식물이다. 구아바, 특히 구아바 잎에는 비타민 C, 마그네슘, 칼륨, 칼슘 등 비타민과 미네랄 등이 많이 함유되어 있으며, 과산화변이억제작용(암예방), 과항당뇨증작용 (당흡수억제, 유사 인슐린 작용-함유하고 있는 폴리페놀 성분) 등이 보고되어 있다.On the other hand, guava is an American tropical plant of the genus Psidium (Myrtaceae). It is a medicinal plant that can utilize leaves, bark and fruit as well as potted plants for healthful and medicinal purposes. Guava, especially guava leaves contain many vitamins and minerals such as vitamin C, magnesium, potassium, and calcium. It is also known to contain many kinds of vitamins and minerals, including peroxidation-inhibiting action (cancer prevention) Polyphenol component) have been reported.
본 발명자들은 자외선 노출로 인한 멜라닌 형성 억제를 통해 피부 흑화를 억제할 뿐만 아니라, 염증성 질환에 효과적인 천연물을 연구하던 중, 구아바의 추출물 또는 이의 분획물에 우수한 멜라닌 억제 효과 및 각종 염증 질환의 유도에 주도적 역할을 하는 T cell 등 염증 세포의 활성화 억제 효능을 발견하고, 이에 기초하여 본 발명을 완성하기에 이르렀다.The present inventors not only inhibited skin blackening through inhibition of melanin formation due to exposure to ultraviolet rays, but also studied melanin inhibitory effects and induction of various inflammatory diseases in Guava extract or its fractions while studying natural products effective for inflammatory diseases The present invention has been accomplished on the basis of this finding.
따라서, 본 발명의 목적은 구아바 추출물 또는 이의 분획물을 포함하는 피부 미백용 또는 염증억제제 조성물을 제공하는 것이다.It is therefore an object of the present invention to provide a skin whitening or antiinflammatory composition comprising guava extract or a fraction thereof.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.
상기와 같은 본 발명의 목적을 달성하기 위해서, 본 발명은 구아바(Psidium guajava) 추출물 또는 이의 분획물을 유효성분으로 포함하는 피부 미백용 조성물을 제공한다.In order to achieve the object of the present invention as described above, the present invention provides a guava (Psidium guajava extract or a fraction thereof as an active ingredient.
본 발명의 일 구현예로, 상기 구아바는 구아바의 잎(Psidium guajava L.)일 수 있다.In one embodiment of the present invention, the guava may be a guava leaf (Psidium guajava L.).
본 발명의 다른 구현예로, 상기 추출물은 구아바를 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 추출할 수 있다.In another embodiment of the present invention, the extract may be obtained by extracting guava with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
본 발명의 또 다른 구현예로, 상기 탄소수 1 내지 4의 알코올은 메탄올 또는 에탄올일 수 있다.In another embodiment of the present invention, the alcohol having 1 to 4 carbon atoms may be methanol or ethanol.
본 발명의 또 다른 구현예로, 상기 분획물은 구아바 추출물을 헥산, 디클로로메탄, 에틸아세테이트, 부탄올로 순차적으로 분획하여 얻은 헥산 분획물, 디클로로메탄 분획물, 에틸아세테이트 분획물 또는 부탄올 분획물일 수 있다.In another embodiment of the present invention, the fraction may be a hexane fraction, a dichloromethane fraction, an ethyl acetate fraction or a butanol fraction obtained by sequentially fractionating a guava extract with hexane, dichloromethane, ethyl acetate or butanol.
본 발명의 또 다른 구현예로, 상기 조성물은 ORAI-1 이온 통로의 저해를 통해 멜라닌 형성을 억제할 수 있다.In another embodiment of the present invention, the composition can inhibit melanin formation through inhibition of the ORAI-1 ion channel.
본 발명의 또 다른 구현예로, 상기 조성물은 티로시나제 활성을 저해할 수 있다.In another embodiment of the present invention, the composition may inhibit tyrosinase activity.
본 발명의 또 다른 구현예로, 상기 조성물은 자외선 노출로 인한 피부 흑화를 억제할 수 있다.In another embodiment of the present invention, the composition can inhibit skin blackening due to ultraviolet exposure.
본 발명의 또 다른 구현예로, 상기 조성물은 약제학적 조성물일 수 있다.In another embodiment of the present invention, the composition may be a pharmaceutical composition.
본 발명의 또 다른 구현예로, 상기 조성물은 화장품학적 조성물일 수 있다.In another embodiment of the present invention, the composition may be a cosmetic composition.
본 발명의 또 다른 구현예로, 상기 조성물은 기능성 식품 조성물일 수 있다.In another embodiment of the present invention, the composition may be a functional food composition.
본 발명은 구아바(Psidium guajava) 추출물 또는 이의 분획물을 유효성분으로 포함하는, 항염증 또는 면역억제용 조성물을 제공한다.The present invention relates to a method for the treatment of psoriasis guajava extract or a fraction thereof as an active ingredient.
본 발명의 일 구현예로, 상기 면역억제는 ORAI-1 이온 통로의 저해를 통해 이루어질 수 있다.In one embodiment of the invention, the immunosuppression may be through inhibition of the ORAI-I pathway.
본 발명의 조성물을 이용하면, 일광(日光) 조사 시 피부 멜라닌 세포 멜라닌 형성으로 인한 피부흑화 시 중요한 역할을 담당하는 Orai-1 이온통로를 억제할 뿐만 아니라 티로시나제 활성을 저해할수 있는 효과를 가진다. 또한, Orai-1은 면역활성에 중요한 칼슘이온 통로이므로 이를 효과적으로 억제하면 각종 염증성 질환을 해결할 수 있는 효과를 가진다.When the composition of the present invention is used, it has an effect of inhibiting tyrosinase activity as well as inhibiting Orai-1 ion channel which plays an important role in skin darkening due to skin melanin cell melanin formation during sunlight irradiation. In addition, Orai-1 is a calcium ion pathway important for immunological activity, and thus it is effective to solve various inflammatory diseases by effectively inhibiting it.
구아바 잎은 현재 식용으로 사용될 만큼 세포독성이 없는 안전한 물질이므로, 자외선에 의한 피부 손상 그리고 기관지천식, 알레르기비염, 아토피피부염 등 염증/면역성 질환 예방 및 치료에 유용하게 사용될 수 있을 것이다.Since guava leaves are safe substances that are not cytotoxic enough to be used for edible purposes, they may be useful for the prevention and treatment of inflammatory / immune diseases such as bronchial asthma, allergic rhinitis and atopic dermatitis.
도 1은 구아바 분획물 중 부탄올 분획물의 ORAI-1 활성 억제 효과를 나타낸 그래프이다.
도 2는 구아바 추출물 및 이의 분획물들의 ORAI-1 이온통로 저해율을 산출한 결과이다.
도 3은 구아바 추출물 및 이의 분획물들의 티로시나제 활성 저해효과를 나타낸 그래프이다.
도 4는 아토피피부염 동물모델에서 관능평가를 통해 구아바 분획물 중 부탄올 분획물의 아토피피부염 치료 효과를 확인한 결과이다.1 is a graph showing the inhibitory effect of ORAI-1 on the butanol fraction of guava fraction.
Figure 2 shows the results of calculating the ORAI-1 ion channel inhibition rate of guava extract and its fractions.
Fig. 3 is a graph showing the inhibitory effect of guava extract and its fractions on tyrosinase activity.
FIG. 4 shows the results of confirming the effect of the butanol fraction of guava fraction on the treatment of atopic dermatitis by sensory evaluation in an atopic dermatitis animal model.
본 발명자들은 여러 천연물들을 대상으로 멜라닌 형성 억제 효과가 있는 새로운 천연물을 찾기 위하여 연구에 몰두하던 중, 구아바 추출물 및 이의 분획물에 ORAI-1 활성을 억제하는 효과가 있다는 것을 확인하고, 이에 기초하여 본 발명을 완성하게 되었다.The inventors of the present invention have found that guava extract and its fractions have an effect of inhibiting ORAI-1 activity while engaging in research to find a new natural product having an effect of inhibiting melanin formation on various natural products, .
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 구아바(Psidium guajava) 추출물 또는 이의 분획물을 유효성분으로 포함하는 피부 미백용 조성물을 제공한다. 이때, 구아바는 구아바의 잎을 사용하는 것이 바람직하다.The present invention relates to a method for the treatment of psoriasis guajava extract or a fraction thereof as an active ingredient. At this time, guava preferably uses guava leaves.
본 발명에서, 구아바 추출물은 천연물로부터 추출물을 추출하는 당업계에 공지된 통상적인 방법에 따라, 즉, 통상적인 온도, 압력의 조건 하에서 통상적인 용매를 사용하여 추출할 수 있다. 예컨대, 본 발명에서, 구아바 추출물은 물, 탄소수 1 내지 4의 알코올 및 이들의 혼합용매로부터 선택된 1종 이상의 용매를 이용할 수 있으며, 바람직하게는 메탄올 또는 에탄올을 이용할 수 있다. 또한, 구아바로부터 추출물을 추출하는 방법은 열수 추출, 냉침 추출, 환류 추출, 초음파 추출 등의 다양한 방법을 통하여 추출할 수 있지만, 이것으로 제한되는 것은 아니다.In the present invention, guava extract can be extracted using conventional solvents known in the art for extracting the extract from natural products, that is, under ordinary temperature and pressure conditions, using a conventional solvent. For example, in the present invention, the guava extract may be at least one solvent selected from water, alcohols having 1 to 4 carbon atoms, and mixed solvents thereof, preferably methanol or ethanol. In addition, the method for extracting the extract from guava may be carried out by various methods such as hot water extraction, cold extraction, reflux extraction, and ultrasonic extraction, but is not limited thereto.
본 발명에서, 구아바 분획물은 구아바를 용매로 추출하여, 추출된 추출액을 여과하고 감압 농축하여 구아바 추출물을 얻은 후, 이를 헥산, 디클로로메탄, 에틸아세테이트, 부탄올을 이용하여 순차적으로 분획하는 단계에 의하여 획득될 수 있으며. 바람직하게는 부탄올 분획물일 수 있다.In the present invention, the guava fraction is obtained by extracting guava with a solvent, filtering the extracted extract, concentrating under reduced pressure to obtain a guava extract, and sequentially fractionating it using hexane, dichloromethane, ethyl acetate and butanol Can be. Preferably a butanol fraction.
본 발명의 일 실시예에서는, 구아바 추출물 및 이의 분획물을 제조한 후(실시예 1 참조), 이들의 ORAI-1 억제 효과를 확인한 결과, 본 발명에 따른 구아바 추출물 또는 이의 분획물이 ORAI-1 이온 통로의 저해 효과가 우수하다는 것을 확인하였다(실시예 2 참조).In one embodiment of the present invention, guava extract and its fractions were prepared (see Example 1), and their ORAI-1 inhibitory effect was confirmed. As a result, the guava extract or its fractions according to the present invention showed an ORAI- (See Example 2). ≪ tb > < TABLE >
본 발명의 다른 실시예에서는, 구아바 추출물 또는 이의 분획물의 티로시나제 활성 억제 효과를 확인한 결과, 본 발명에 따른 구아바 추출물 또는 이의 분획물이 대조군에 비하여 우수한 티로시나제 활성 억제 효과가 있음을 확인하였다(실시예 3 참조).In another embodiment of the present invention, it was confirmed that guava extract or its fractions had an inhibitory effect on tyrosinase activity, and the guava extract or its fractions according to the present invention had a superior tyrosinase activity inhibitory effect as compared with the control group (see Example 3) ).
따라서, 본 발명에 따른 구아바 추출물 또는 이의 분획물은 ORAI-1 이온 통로의 저해 및 티로시나제 활성 억제를 통해 자외선 노출로 인한 멜라닌 형성을 억제하는 효과를 가지는바, 피부의 흑화를 억제하는 등 피부 미백을 위한 용도로 유용하게 이용될 수 있다.Therefore, the guava extract or the fractions thereof according to the present invention have an effect of inhibiting melanin formation due to exposure to ultraviolet rays through inhibition of ORAI-1 ion channel and inhibition of tyrosinase activity, And can be usefully used for applications.
이에, 본 발명의 피부 미백용 조성물은 약제학적 조성물의 형태일 수 있으며, 약제학적 조성물은 유효성분으로서 구아바 추출물 또는 이의 분획물을 포함하고 약제학적으로 허용되는 담체를 더 포함할 수 있다. 본 발명의 약제학적 조성물에 포함되는 약제학적으로 허용되는 담체로는 식염수, 완충 식염수, 물, 글리세롤 및 에탄올 등이 있으나 이에 한정되지 않는다.Accordingly, the composition for whitening skin of the present invention may be in the form of a pharmaceutical composition, and the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier containing guava extract or its fractions as an active ingredient. Pharmaceutically acceptable carriers in the pharmaceutical compositions of the present invention include, but are not limited to, saline, buffered saline, water, glycerol, and ethanol.
본 발명의 약제학적 조성물은 경구 또는 비경구투여를 위한 어떠한 제형으로도 제조될 수 있으며, 바람직하게는 피부외용 제형을 갖는다. 피부외용 제형은 파우더, 젤, 연고, 크림, 액체 또는 에어로졸 제형일 수 있으나, 이것으로 제한되는 것은 아니다.The pharmaceutical composition of the present invention can be prepared into any formulation for oral or parenteral administration, and preferably has an external preparation for skin. The dermatological formulations can be, but are not limited to, powders, gels, ointments, creams, liquids or aerosol formulations.
본 발명의 약제학적 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구투여(예를 들어, 피부 도포, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 시간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다.The pharmaceutical composition of the present invention may be administered orally or parenterally (for example, skin application, intravenous injection, subcutaneous injection, intraperitoneal injection or topical application) depending on the intended method, The severity of the disease, the form of the drug, the route of administration, and the time, but may be suitably selected by those skilled in the art.
본 발명의 약제학적 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 약제학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dosage level is determined depending on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
구체적으로, 본 발명의 약제학적 조성물의 유효량은 환자의 연령, 성별, 상태, 체중, 체내에서 활성 성분의 흡수도, 불활성율 및 배설속도, 질병종류, 병용되는 약물에 따라 달라질 수 있으며, 일반적으로는 체중 1㎏ 당 0.001 내지 150 mg, 바람직하게는 0.01 내지 100 mg을 매일 또는 격일 투여하거나 1일 1 내지 3회로 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, body weight, absorbency of the active ingredient, inactivity and excretion rate, disease type, May be administered at a daily dose of 0.001 to 150 mg, preferably 0.01 to 100 mg, per 1 kg of body weight, or one to three divided doses per day. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
또한, 본 발명의 피부 미백용 조성물은 화장품학적 조성물의 형태일 수 있으며, 화장품학적 조성물은 유효성분으로서 구아바 추출물 또는 이의 분획물을 포함할 수 있다.In addition, the skin whitening composition of the present invention may be in the form of a cosmetic composition, and the cosmetic composition may contain guava extract or a fraction thereof as an active ingredient.
본 발명의 화장품학적 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 상세하게는, 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.The cosmetic composition of the present invention may be prepared into any of the formulations conventionally produced in the art, and may be prepared, for example, as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, But are not limited to, cleansing, oils, powder foundations, emulsion foundations, wax foundations and sprays. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.
본 발명의 화장품학적 조성물에 함유된 화장품학적으로 유효한 담체는 제형에 따라, 당업계에서 통상적으로 이용되는 담체가 이용될 수 있다. 본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.The cosmetically effective carrier contained in the cosmetic composition of the present invention may be a carrier conventionally used in the art depending on the formulation. When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로 플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다. In the case where 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. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 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 present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 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. In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters.
본 발명의 화장품학적 조성물에 포함되는 성분은 유효 성분과 담체 성분 이외에, 화장품학적 조성물에 통상적으로 이용되는 성분들을 포함하며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제를 포함할 수 있다.The ingredients included in the cosmetic composition of the present invention include, in addition to the active ingredient and the carrier ingredient, the ingredients conventionally used in cosmetic compositions and include conventional ingredients such as antioxidants, stabilizers, solubilizers, vitamins, May include adjuvants.
더욱이, 본 발명의 피부 미백용 조성물은 미백을 예방 또는 개선하는 기능성 식품 조성물의 형태일 수 있으며, 기능성 식품 조성물은 유효성분으로서 구아바 추출물 또는 이의 분획물을 포함할 수 있다.Furthermore, the skin whitening composition of the present invention may be in the form of a functional food composition for preventing or improving whitening, and the functional food composition may contain guava extract or its fractions as an active ingredient.
상기 식품의 종류에는 특별한 제한은 없다. 상기 유효성분을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of foods to which the active ingredient can be added include dairy products including dairy products, meat, sausage, bread, biscuits, rice cakes, chocolates, snacks, confectionery, pizza, ramen noodles, other noodles, gums, ice cream, , Beverages, alcoholic beverages and vitamin complexes, dairy products, and dairy products, all of which include health functional foods in a conventional sense.
본 발명의 기능성 식품 조성물에서 유효성분을 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 조성물은 원료에 대하여 15 중량% 이하, 바람직하게는 10 중량% 이하의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있다.In the functional food composition of the present invention, the active ingredient may be directly added to the food or may be used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (for prevention or improvement). In general, the composition of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, in the production of food or beverage. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range.
본 발명의 기능성 식품 조성물은 지시된 비율로 필수 성분으로서 상기 유효성분을 함유하는 것 이외에 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 당업자의 선택에 의해 적절하게 결정될 수 있다.The functional food composition of the present invention is not particularly limited to the ingredients other than those containing the active ingredient as the essential ingredient in the indicated ratio and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary drinks . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above . The ratio of the above-mentioned natural carbohydrate can be appropriately determined by a person skilled in the art.
상기 외에 본 발명의 기능성 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율 또한 당업자에 의해 적절히 선택될 수 있다.In addition to the above, the functional food composition of the present invention may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, And salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. These components may be used independently or in combination. The ratios of these additives can also be appropriately selected by those skilled in the art.
또한, 본 발명에 따른 구아바 추출물 또는 이의 분획물은 ORAI-1 이온 통로의 저해를 통한 면역저해 효과도 가지는바, 자외선에 의한 피부 손상 그리고 기관지천식, 알레르기비염, 아토피피부염 등 염증/면역성 질환의 예방, 개선 및 치료에 유용하게 사용될 수 있을 것이다.In addition, the guava extract or its fractions according to the present invention have an immunosuppressive effect through inhibition of ORAI-1 ion channel, and can be used for prevention of skin damage due to ultraviolet rays, prevention of inflammatory / immune diseases such as bronchial asthma, allergic rhinitis, And may be useful for improvement and treatment.
본 발명의 또 다른 실시예에서는, 아토피피부염 동물모델에서 구아바 부탄올 분획물의 치료 효과를 확인한 결과, 현재 아토피피부염 치료에 가장 흔하고도 효과적으로 사용되는 1% hydrocortisone 연고보다도 훨씬 우수한 치료 효과를 나타냄을 확인하였다(실시예 4 참조).In another embodiment of the present invention, the therapeutic effect of the guava butanol fraction in the atopic dermatitis animal model has been confirmed to show a far superior therapeutic effect than the 1% hydrocortisone ointment currently used most effectively and effectively for the treatment of atopic dermatitis See Example 4).
이에, 본 발명은 구아바(Psidium guajava) 추출물 또는 이의 분획물을 유효성분으로 포함하는, 항염증 또는 면역억제용 조성물을 제공한다. 본 발명의 항염증 또는 면역억제용 조성물도 약제학적, 화장품학적, 또는 기능성 식품 조성물의 형태로 이용될 수 있고, 이는 전술한 바와 동일한 내용인바, 자세한 설명은 생략한다.Accordingly, the present invention relates to a method for producing guajava extract or a fraction thereof as an active ingredient. The anti-inflammatory or immunosuppressive composition of the present invention can also be used in the form of pharmaceutical, cosmetic, or functional food composition, which is the same as described above, and thus a detailed description thereof will be omitted.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.
[실시예][Example]
실시예 1. 구아바 추출물 및 분획물의 제조Example 1. Preparation of guava extract and fractions
구아바 잎(Psidium guajava L.)을 세절한 다음, 70% MeOH 3L를 가열하여 3시간 동안 두 번 추출하고, 여과하여 용매와 물을 증발시켜 분말로 된 구아바 추출물을 제조하였다. 이후, 상기 구아바 잎 MeOH 추출물 분말에 물을 가하고 헥산(Hexane)을 부가하여 진탕하여 유기용매층과 물층을 1차 분리하고 상기 물층에 디클로로메탄(CH2Cl2)을 다시 부가하여 진탕하여 유기용매층과 물층을 2차 분리하고 상기 물층에 에틸아세테이트(EtOAc)를 다시 부가하여 유기용매층과 물층을 3차 분리하고 상기 물층에 부탄올(BuOH)을 다시 부가하여 유기용매층과 물층을 4차 분리하여 각각의 헥산 분획물, 디클로로메탄 분획물, 에틸아세테이트 분획물 및 부탄올 분획물을 회수하였다.The guava leaves (Psidium guajava L.) were cut three times, and then 3 L of 70% MeOH was heated and extracted twice for 3 hours, and the solvent and water were evaporated by filtration to prepare powdered guava extract. Thereafter, water is added to the Guava leaf MeOH extract powder, hexane is added thereto, and the mixture is shaken to separate the organic solvent layer and the water layer. The dichloromethane (CH 2 Cl 2 ) is again added to the water layer, Layer and the water layer are separated from each other and ethyl acetate (EtOAc) is added again to the water layer to separate the organic solvent layer and the water layer from each other, and then the butanol (BuOH) is again added to the water layer to separate the organic solvent layer and the water layer The respective hexane fractions, dichloromethane fractions, ethyl acetate fractions and butanol fractions were recovered.
실시예 2. 구아바 분획물의 ORAI-1 억제 효과 확인Example 2. Confirmation of ORAI-1 Inhibitory Effect of Guava Fractions
실시예 1을 통해 제조된 구아바 메탄올 추출물, 헥산 분획물, 디클로로메탄 분획물, 에틸아세테이트 분획물 및 부탄올 분획물의 ORAI-1 저해효과를 측정하였다. 측정을 위해 면역세포에 발현되어 있는 인간 ORAI-1 단백질을 클로닝한 뒤, 이를 HEK-293T 세포주에 과발현시켜 세포 내 칼슘 전류를 실시간으로 직접 측정할 수 있는 팻취클램프 (patch clamp) 기법을 이용하여 측정하였다.The ORAI-1 inhibitory effect of the guava methanol extract, hexane fraction, dichloromethane fraction, ethyl acetate fraction and butanol fraction prepared in Example 1 was measured. The human ORAI-1 protein expressed in the immune cells was overexpressed in the HEK-293T cell line to measure the intracellular calcium current in real time using a patch clamp technique Respectively.
Orai-1이 과발현된 HEK-293T 세포 주에 대한 팻취클램프 기법은 세포전체 막전압 고정법 (이하 whole cell patch clamp)으로 실시하였다. 유리전극은 저항 2~4 Mohm의 것을 사용하였다. Patch clamp 증폭기 (Axopatch 700B, Axon instruments, USA)를 통해서 나온 신호는 Axoscope 10.4 및 Clampfit 10.4를(cAxon instruments, USA) 통해서 관찰하였다. 고정 전압과 자극전압을 가하고 이때의 전류 반응을 기록하고 저장하기 위해서 pClamp software (v10.4)와 동작 클럭이 3.2GHz인 개인 컴퓨터에 장착된 아날로그-디지털 변화기 (Digidata-1440A, Axon instruments, USA)를 이용하였다. 막 전압고정 실험에 얻어진 결과는 clampfit v10.4, origin (Microcal software, USA)등을 이용하여 분석, 처리하였다.The patch clamp technique for Orai-1 overexpressed HEK-293T cell line was performed by whole cell patch clamp. Glass electrodes with resistances of 2 to 4 Mohm were used. Signals from a patch clamp amplifier (Axopatch 700B, Axon instruments, USA) were observed through Axoscope 10.4 and Clampfit 10.4 (cAxon instruments, USA). (Digidata-1440A, Axon instruments, USA) equipped with a pClamp software (v10.4) and a personal computer with an operating clock of 3.2GHz to record and store the current response at a fixed voltage and excitation voltage, Respectively. The results obtained for the membrane voltage clamp were analyzed and processed using clampfit v10.4, origin (Microcal software, USA).
Orai-1을 통한 전류를 측정하기 위해 세포 밖 용액은 135 mM NaCl, 3.6 mM KCl, 1 mM MgCl2, 10 mM CaCl2, 5 mM D-glucose, 10 mM HEPES가 포함된 pH7.4 용액을 사용하였고, 파이펫 용액은 130 mM Cs-Glutamate, 20 mM BAPTA, 1 mM MgCl2, 3 mM MgATP, 0.002 mM Sodiumpyruvate, 20 mM HEPES가 포함된 pH 7.2인 용액을 사용하였다. Orai-1 이온통로를 활성화시키기 위해 20μM 이노시톨 삼인산 (InsP3)을 파이펫 용액에 처리해 주었다.To measure the current through Orai-1, the extracellular solution was pH 7.4 solution containing 135 mM NaCl, 3.6 mM KCl, 1 mM MgCl 2 , 10 mM CaCl 2 , 5 mM D-glucose, and 10 mM HEPES And the pipette solution used was a solution of pH 7.2 containing 130 mM Cs-Glutamate, 20 mM BAPTA, 1 mM MgCl 2 , 3 mM MgATP, 0.002 mM sodium pyruvate and 20 mM HEPES. To activate the Orai-1 ion channel, 20 μM inositol triphosphate (InsP 3 ) was added to the pipet solution.
그 결과, 도 1 및 도 2에 나타낸 바와 같이, 구아바 추출물 또는 이의 분획물들이 ORAI-1 이온 통로의 저해 효과가 있음을 확인할 수 있었고, 특히 구아바 부탄올 분획물이 ORAI-1 활성 억제에 매우 탁월한 효과가 있음을 확인할 수 있었다.As a result, as shown in Figs. 1 and 2, it was confirmed that the guava extract or its fractions had an inhibitory effect on the ORAI-1 ion channel, and the guava butanol fraction had an excellent effect for inhibiting ORAI-1 activity .
실시예 3. 구아바 추출물 및 분획물의 티로시나제 활성 저해효과 확인Example 3. Confirmation of tyrosinase activity inhibitory effect of guava extract and fractions
실시예 1을 통해 제조된 구아바 메탄올 추출물, 헥산 분획물, 디클로로메탄(염화메틸렌) 분획물, 에틸아세테이트 분획물 및 부탄올 분획물의 티로시나제 저해효과를 측정하기 위해, 하기와 같이 실험을 진행하였다.In order to measure the inhibition effect of the guava methanol extract, hexane fraction, dichloromethane (methylene chloride) fraction, ethyl acetate fraction and butanol fraction produced through Example 1, tyrosinase inhibition was tested as follows.
티로시나제 (tyrosinase)는 L-DOPA로부터 멜라닌을 형성시키는데 중요한 역할을 담당하는 효소로서, 기질인 L-DOPA를 티로시나제에 처리함과 동시에 구아바 추출물 및 분획물을 넣어주어 티로시나제에 의한 멜라닌 형성이 구아바 추출물/분획물 처리 전에 비해 얼마나 억제되는지 알아보는 실험을 진행하였다. 보다 구체적으로, sodium phosphate buffer (pH 6.8, 1/15 M; 1.2 mL), Levodopa (L-DOPA) (1.5 mM; 0.5 mL) 그리고 구아바 추출물 및 분획물 (10 mg/1 mL; 0.2 mL)이 혼합되어 있는 시료를 티로시나제가 들어가 있는 용액에 넣고 30℃에서 10분간 반응시켜 주었다. 반응이 일어나 멜라닌이 형성되면 이를 microplate reader를 이용하여 475nm에서 흡광도를 측정하였다. 대조군으로는 200μg/mL의 코지산(kojic acid)을 사용하였다.Tyrosinase is an enzyme that plays an important role in the formation of melanin from L-DOPA. It treats L-DOPA, a substrate, with tyrosinase and guava extract and fractions to induce melanin formation by tyrosinase. Experiments were carried out to see how much it was suppressed compared to before treatment. More specifically, a mixture of sodium phosphate buffer (pH 6.8, 1/15 M; 1.2 mL), Levodopa (L-DOPA) (1.5 mM; 0.5 mL) and guava extract and fractions (10 mg / The sample was placed in a solution containing tyrosinase and reacted at 30 ° C for 10 minutes. When the reaction occurred and melanin was formed, the absorbance was measured at 475 nm using a microplate reader. As a control, 200 μg / mL of kojic acid was used.
그 결과, 도 3에 나타낸 바와 같이, 대조군에 비하여 구아바 추출물 또는 이의 분획물들이 티로시나제 활성 억제 효과가 있음을 확인할 수 있었고, 특히 구아바 부탄올 분획물이 티로시나제 활성 억제에 매우 탁월한 효과가 있음을 확인할 수 있었다.As a result, as shown in FIG. 3, it was confirmed that Guava extract or its fractions had an inhibitory effect on tyrosinase activity as compared with the control group. In particular, it was confirmed that guava butanol fraction had an excellent effect for inhibiting tyrosinase activity.
실시예 4. 동물모델을 이용한 아토피피부염 치료 효과 확인Example 4. Confirmatory effect of atopic dermatitis treatment using animal model
실시예 1을 통해 제조된 구아바 부탄올 분획물의 아토피피부염 동물모델에서 치료 효과를 관찰 하였다.The therapeutic effect of the guava butanol fraction prepared in Example 1 was observed in an animal model of atopic dermatitis.
본 실험에 이용된 NC/Nga 마우스는 자발적 아토피피부염 유발 모델로 잘 알려져 있으나 자발적인 피부염 유도 비율이 낮고, 유도된 아토피피부염의 강도에도 차이가 심하여 본 실험에서는 집먼지진드기 항원을 포함하는 연고(AD연고®, Biostir)를 이용하여 2주간 아토피피부염을 유발한 후 1주간 구아바 부탄올 추출물로 치료하였다. 치료 후 관능평가(Modified SCORAD score)를 실시하여 아토피피부염 치료 효과를 평가 하였다.The NC / Nga mice used in this experiment is an ointment that contains the house dust mite allergen in spontaneous atopic dermatitis is well known, but a mortar model with low spontaneous dermatitis induction rate, the severe differences in the intensity of the induced atopic dermatitis experiments (AD ointment ® , Biostir) to induce atopic dermatitis for 2 weeks and then treated with guava butanol extract for 1 week. The modified SCORAD score was used to evaluate the treatment effect of atopic dermatitis.
4-1. 시약 및 실험 동물 준비4-1. Preparation of reagents and experimental animals
치료효과 평가를 위해 1% hydrocortisone로션(락틱케어 로션, 글락소 스미스클라인)와 기제인 글리세린(안진약품)을 준비하였고, 실험 시료는 구아바 부탄올 분획물을 글리세린에 1%로 용해시킨 용액을 준비 하였다. 아토피피부염 유도를 위해 Biostir사의 AD연고®, 4%SDS(Sodium dodecyl sulfate), 제모크림(Veet®, 옥시래킷벤키져)을 준비하였다. To evaluate the therapeutic effect, 1% hydrocortisone lotion (lactic care lotion, GlaxoSmithKline) and glycerin (Ninjin Pharma) were prepared. The test sample was prepared by dissolving 1% of guava butanol fraction in glycerin. ® Biostir's AD ointment for atopic dermatitis induction, 4% SDS (Sodium dodecyl sulfate ), hair removal cream was prepared (Veet ®, oxy kitben kijyeo below).
실험동물은 4주령의 암컷 NC/Nga 마우스(SLC Japan, Shizuoka, Japan)를 ㈜중앙실험동물에서 공급받아 고형사료와 물을 자유롭게 섭취 할 수 있도록 공급하고 실온 22±2℃, 상대습도 50~65%, 조도 200 lux (8시간 점등, 20시간 소등)를 계속 유지하면서 SPF환경에서 1주일간 실험실 환경에 적응시킨 후 실험에 사용하였다.Experimental animals were fed with 4-week-old female NC / Nga mice (SLC Japan, Shizuoka, Japan) and fed with solid feed and water freely. They were kept at room temperature 22 ± 2 ℃, %, Illuminance 200 lux (8 hours lighting, 20 hours off), and adapted to the laboratory environment for 1 week in SPF environment.
4-2. 아토피피부염 유도 4-2. Induction of atopic dermatitis
NC/Nga마우스를 마취시킨 후 전기 제모기로 귀부터 등의 상부까지 제모 한 후 제모크림으로 털을 완벽하게 제거하고 헤어드라이어로 완전히 건조 시킨 후 AD연고® 100mg을 평평한 스틱을 이용하여 제모 부위에 도포하였다. 2회 도포시 부터는 피부장벽 파괴를 위해 제모크림을 이용하지 않고 4%SDS용액 150㎕을 분무하고 4시간 자연건조 시킨 뒤 AD연고를 도포 하였다. 주3회 2주간 AD연고® 를 도포한 후 관능평가를 실시하였다.After anesthesia, the NC / Nga mice after complete removal of hair after hair removal cream a hair removal up to the top, such as electric epilator from ear to fully dry with a hair dryer applied to the hair removal portion the AD ointment ® 100mg using a flat stick Respectively. From 2 times of application, 150 ㎕ of 4% SDS solution was sprayed without using hair removal cream to break the skin barrier, followed by natural drying for 4 hours and then applying AD ointment. After applying AD Ointment ® three times a week for two weeks, sensory evaluation was carried out.
관능평가로 아토피피부염에서 일반적으로 사용되는 임상적 육안평가법인 Modifide SCORAD score를 사용하였고 실험자가 육안으로 관찰한 4개 항목 [홍반/출혈(erythema/hemorrhage), 부종(edema), 인설/건조(scaling/dryness), 찰과상/미란(excoriation/erosion)]에 0점(좋음), 1점(조금 나쁨), 2점(나쁨), 3점(매우나쁨)으로 점수를 부여하여 총점이 8점 이상인 쥐를 선택하여 4개 군으로 나누어 실험을 진행하였다. 각 군의 평균점수는 10점 이었다.Modifide SCORAD score, which is a general clinical evaluation method for atopic dermatitis, was used as a sensory test. Four items (erythema / hemorrhage, edema, scaling, (dry), scored / excoriated / erosion] were scored as 0 (good), 1 (poor), 2 (poor), and 3 (very bad) Were selected and divided into four groups. The average score of each group was 10 points.
4-3. 구아바 부탄올 분획물의 효능 평가4-3. Evaluation of efficacy of guava butanol fraction
제1군은 정상군으로 제모 이외에 아무런 처치를 하지 않았고 제2군은 양성대조군으로 2주간 아토피 유도 후 아무런 처치를 하지 않았다. 제3군은 음성대조군으로 기제인 글리세린을 1일1회 1주일 동안 귀와 등에 도포하였다. 실험군인 제4군에는 글리세린에 1% 구아바 부탄올분획을 용해시킨 용액을 같은 방법으로 도포하였고 제5군에는 치료효과 비교를 위해 1% hydrocortisone 로션을 같은 방법으로 도포 한 후 마지막 도포 다음날 관능평가를 실시하였다.
그 결과, 도 4에 나타낸 바와 같이, 도포 7일 후 관능평가 결과 1% 구아바 부탄올 분획물을 글리세린에 용해시킨 용액을 도포한 제4군의 SCORAD score점수는 2점으로 양성대조군인 제2군(SCORAD score 10점)과 음성대조군인 제3군(SCORAD score 7점)에 비해 확연히 낮아졌고 심지어 현재 아토피피부염 치료에 가장 흔하고도 효과적으로 사용되는 1% hydrocortisone 연고를 도포한 제5군(SCORAD score 5점)에 비해서도 SCORAD score가 확연히 낮아진 것을 관찰 할 수 있었다. As a result, as shown in Fig. 4, the SCORAD score score of the fourth group in which a 1% guava butanol fraction was dissolved in glycerin was measured in a sensory evaluation after 7 days of application, and the SCORAD score score of the second group (SCORAD (SCORAD score, 5 points), which is the most common and effective treatment for atopic dermatitis, and 1% hydrocortisone ointment, The SCORAD score was significantly lower than that of the control group.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해되어야 한다.It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.
Claims (13)
Psidium guajava ) extract or a fraction thereof as an active ingredient.
상기 구아바는 구아바의 잎(Psidium guajava L.)인 것을 특징으로 하는, 조성물.
The method according to claim 1,
The guava is a guava leaf ( Psidium guajava L.). ≪ / RTI >
상기 구아바 추출물은 구아바를 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 추출한 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the guava extract is obtained by extracting guava with water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.
상기 탄소수 1 내지 4의 알코올은 메탄올 또는 에탄올인 것을 특징으로 하는, 조성물.
The method of claim 3,
Wherein the alcohol having 1 to 4 carbon atoms is methanol or ethanol.
상기 분획물은 구아바 추출물을 헥산, 디클로로메탄, 에틸아세테이트, 부탄올로 순차적으로 분획하여 얻은 헥산 분획물, 디클로로메탄 분획물, 에틸아세테이트 분획물 또는 부탄올 분획물인 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the fraction is a hexane fraction, a dichloromethane fraction, an ethyl acetate fraction or a butanol fraction obtained by sequentially fractionating a guava extract with hexane, dichloromethane, ethyl acetate or butanol.
상기 조성물은 ORAI-1 이온 통로의 저해를 통해 멜라닌 형성을 억제하는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein said composition inhibits melanogenesis through inhibition of the ORAI-I pathway.
상기 조성물은 티로시나제 활성을 저해하는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition inhibits tyrosinase activity.
상기 조성물은 자외선 노출로 인한 피부 흑화를 억제하는 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein said composition inhibits skin blackening due to ultraviolet exposure.
상기 조성물은 약제학적 조성물인 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition is a pharmaceutical composition.
상기 조성물은 화장품학적 조성물인 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition is a cosmetic composition.
상기 조성물은 기능성 식품 조성물인 것을 특징으로 하는, 조성물.
The method according to claim 1,
Wherein the composition is a functional food composition.
Psidium guajava extract or a fraction thereof as an active ingredient.
상기 면역억제는 ORAI-1 이온 통로의 저해를 통해 이루어지는 것을 특징으로 하는, 조성물.13. The method of claim 12,
Wherein the immunosuppression is through inhibition of the ORAI-I pathway.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018056497A1 (en) * | 2016-09-26 | 2018-03-29 | 주식회사 프롬바이오 | Immunopotentiating food composition comprising amla fruit extract and guava leaf extract |
| KR101929500B1 (en) | 2018-07-27 | 2019-03-14 | 재단법인 전남생물산업진흥원 | Nano emulsion composition of guava and producing method thereof |
| WO2020013571A1 (en) * | 2018-07-09 | 2020-01-16 | 주식회사 레모넥스 | Pharmaceutical composition and functional health food for preventing or treating macular degeneration |
| JP2021113173A (en) * | 2020-01-20 | 2021-08-05 | 日本メナード化粧品株式会社 | Interleukin 37 expression promoter |
| CN114796319A (en) * | 2022-03-22 | 2022-07-29 | 山东第一医科大学(山东省医学科学院) | Preparation method and application of guava leaf extract |
| KR102472487B1 (en) | 2022-06-14 | 2022-12-01 | (주)올바름디앤비 | Cosmetic composition comprising natural extract mixture |
-
2015
- 2015-10-05 KR KR1020150139525A patent/KR20160056268A/en not_active Ceased
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018056497A1 (en) * | 2016-09-26 | 2018-03-29 | 주식회사 프롬바이오 | Immunopotentiating food composition comprising amla fruit extract and guava leaf extract |
| WO2020013571A1 (en) * | 2018-07-09 | 2020-01-16 | 주식회사 레모넥스 | Pharmaceutical composition and functional health food for preventing or treating macular degeneration |
| US11633447B2 (en) | 2018-07-09 | 2023-04-25 | Lemonex Inc. | Pharmaceutical composition and functional health food for preventing or treating macular degeneration |
| KR101929500B1 (en) | 2018-07-27 | 2019-03-14 | 재단법인 전남생물산업진흥원 | Nano emulsion composition of guava and producing method thereof |
| JP2021113173A (en) * | 2020-01-20 | 2021-08-05 | 日本メナード化粧品株式会社 | Interleukin 37 expression promoter |
| CN114796319A (en) * | 2022-03-22 | 2022-07-29 | 山东第一医科大学(山东省医学科学院) | Preparation method and application of guava leaf extract |
| KR102472487B1 (en) | 2022-06-14 | 2022-12-01 | (주)올바름디앤비 | Cosmetic composition comprising natural extract mixture |
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