KR102039608B1 - Composition including midodrine and its uses - Google Patents
Composition including midodrine and its uses Download PDFInfo
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- KR102039608B1 KR102039608B1 KR1020170145666A KR20170145666A KR102039608B1 KR 102039608 B1 KR102039608 B1 KR 102039608B1 KR 1020170145666 A KR1020170145666 A KR 1020170145666A KR 20170145666 A KR20170145666 A KR 20170145666A KR 102039608 B1 KR102039608 B1 KR 102039608B1
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Abstract
본 발명은 미도드린을 유효성분으로 포함하는 조성물을 제공한다. 본 발명의 조성물은 피부 미백, 주름 개선 효과를 제공한다. 또한 본 발명의 조성물은 피부장벽 강화 및 피부 염증 예방 또는 치료 효과를 제공한다. The present invention provides a composition comprising midodrin as an active ingredient. The composition of the present invention provides a skin whitening, wrinkle improvement effect. In addition, the composition of the present invention provides a skin barrier strengthening and skin inflammation prevention or treatment effect.
Description
본 발명은 미도드린을 포함하는 조성물 및 이의 용도에 대한 것이다. 더욱 상세하게는 알파 교감신경 자극제의 일종인 미도드린을 유효성분으로 포함하여 피부 미백, 주름 개선효과와 더불어 피부 장벽 보호 및 피부 항염증 효과를 구현할 수 있는 화장료 조성물, 약제학적 조성물 및 식품 조성물에 관한 것이다.The present invention is directed to a composition comprising midodrine and its use. More specifically, the present invention relates to a cosmetic composition, a pharmaceutical composition, and a food composition, which include mididorin, which is a kind of alpha sympathetic nerve stimulant, as an active ingredient, which can realize skin whitening, wrinkle improvement, skin barrier protection, and skin anti-inflammatory effect. will be.
기능성 화장품이란 피부의 미백에 도움을 주는 제품, 피부의 주름 개선에 도움을 주는 제품, 피부를 곱게 태워주거나 자외선으로부터 피부를 보호하는 데 도움을 주는 제품 등으로 정의하고 있다. 또한 기능성 화장품은 특정한 피부의 관리와 예방을 위해 특정 기능을 강조해 만든 기초 화장품이며, 유전적, 환경적 요인에 의한 각종 피부 질환의 예방과 적당한 관리를 위한 화장품을 뜻한다. 또한 기능성 화장품이 일반 화장품과 다른 점은 화장품의 생리 활성적인 효능과 효과가 강조된 전문적인 기능성을 갖는다는 점이다. 다시 말해 단순히 외모를 아름답게 해주는 수준보다는 피부보호 및 피부 상태의 개선이라는 더 높은 차원의 효능과 효과를 갖는 제품이라고 할 수 있다.Functional cosmetics are defined as products that help to whiten the skin, products that help improve wrinkles on the skin, products that help to burn the skin finely or protect the skin from ultraviolet rays. In addition, functional cosmetics are basic cosmetics made by emphasizing specific functions for the management and prevention of specific skin, and mean cosmetics for the prevention and proper management of various skin diseases caused by genetic and environmental factors. In addition, functional cosmetics are different from general cosmetics in that they have professional functionality that emphasizes the bioactive effects and effects of cosmetics. In other words, it is a product that has a higher level of efficacy and effect of protecting skin and improving skin condition than simply beautifying the appearance.
기능성 화장품의 종류로는 미백 화장품, 주름 개선 화장품, 자외선 차단 화장품, 여드름 개선 화장품, 각질 제거용 화장품 등이 있다.Examples of functional cosmetics include whitening cosmetics, wrinkle improving cosmetics, sun protection cosmetics, acne improving cosmetics, and exfoliating cosmetics.
현대 사회는 과거에 없었던 다양한 피부 질환, 특히 아토피 피부염이나 기타 원인 불명의 자가면역성 피부 질환들이 발생하고 있고, 이와 같은 질환을 예방하거나 치료할 수 있는 약물에 관한 연구가 활발히 진행되고 있다.In modern society, various skin diseases such as atopic dermatitis and other unknown autoimmune skin diseases are occurring, and researches on drugs that can prevent or treat such diseases are actively conducted.
종래 상업화된 기능성 화장품들과 그의 연구개발 동향들을 살펴보면, 대부분 피부 미백과 주름 개선, 보습 등의 기능에 집중되어 있다. 단순 피부염, 아토피 피부염 등 피부 질환에 대한 예방 및 개선에 적용될 수 있는 기능성 성분 및 기능성 화장품에 대한 기술 개발은 미미한 실정이다. 아울러 피부 염증 예방 및 치료를 위한 새로운 약리학적 활성 성분의 탐색에 관한 시도도 꾸준히 이어지고 있으나, 큰 진전을 이루지 못하고 있다. Looking at the conventional commercialized functional cosmetics and their research and development trends, most of them focus on functions such as skin whitening, wrinkle improvement, and moisturizing. The development of technology for functional ingredients and functional cosmetics that can be applied to the prevention and improvement of skin diseases such as simple dermatitis and atopic dermatitis is insignificant. Attempts have also been made to explore new pharmacologically active ingredients for the prevention and treatment of skin inflammation, but have not made great progress.
따라서, 종래의 미백과 주름 개선 등의 기능과 더불어 다양한 피부 질환 등을 예방 및/또는 개선할 수 있는 기능성 화장품 및 그러한 피부질환의 예방 및 치료 효과를 갖는 새로운 개념의 약물이 개발된다면 삶의 질 향상에 도움이 될 것이다.Therefore, if functional cosmetics that can prevent and / or improve various skin diseases and the like, as well as conventional whitening and wrinkle improvement, and a new concept of a drug having a preventive and therapeutic effect on such skin diseases, quality of life is improved. Will help.
이에 본 발명자는 종래 저혈압 치료제로 사용되었던 알파 교감신경 자극제의 일종인 미도드린이 놀랍게도 피부 미백, 주름개선 그리고 피부 염증의 예방 및 치료에도 우수한 효과를 나타냄을 발견하고 본 발명을 완성하기에 이르렀다.Accordingly, the inventors have found that midodrin, a kind of alpha sympathetic stimulant, which has been used as a conventional hypotension therapeutic agent, surprisingly shows excellent effects on skin whitening, wrinkle improvement and prevention and treatment of skin inflammation, and has completed the present invention.
본 발명의 목적은 미도드린을 유효성분으로 포함하는 피부 미백 및/또는 주름개선용 화장료 조성물을 제공하기 위한 것이다.It is an object of the present invention to provide a cosmetic composition for skin whitening and / or anti-wrinkle comprising midoderine as an active ingredient.
본 발명의 다른 목적은 미도드린을 포함하는 피부 미백 및/또는 주름개선용 식품 조성물을 제공하기 위한 것이다.Another object of the present invention is to provide a food composition for skin whitening and / or anti-wrinkle comprising midodrin.
본 발명의 또 다른 목적은 미도드린을 유효성분으로 포함하는 피부 장벽 강화 및/또는, 피부 염증 예방 및/또는 개선용 화장료 조성물을 제공하기 위한 것이다.Still another object of the present invention is to provide a cosmetic composition for strengthening and / or preventing skin inflammation and / or improving skin barrier including midoderin as an active ingredient.
본 발명의 또 다른 목적은 미도드린을 포함하는 피부 장벽 강화 및/또는, 피부 염증 예방 또는 개선용 식품 조성물을 제공하기 위한 것이다.Still another object of the present invention is to provide a food composition for strengthening and / or preventing or improving skin inflammation, including a midorthrin.
본 발명의 또 다른 목적은 미도드린을 유효성분으로 포함하는 염증성 피부질환 치료 및/또는 예방용 약학적 조성물을 제공하기 위한 것이다.Still another object of the present invention is to provide a pharmaceutical composition for treating and / or preventing inflammatory skin diseases, including middorin as an active ingredient.
본 발명은 미도드린(midodrine)을 유효성분으로 포함하는 피부 미백 및/또는 주름개선용 화장료 조성물을 제공한다.The present invention provides a cosmetic composition for skin whitening and / or anti-wrinkle comprising midodrine as an active ingredient.
상기 미도드린은 상기 피부 미백 및/또는 주름개선용 화장료 조성물에 1 내지 10000μM 농도로 포함될 수 있다. The middorin may be included at a concentration of 1 to 10000 μM in the cosmetic composition for skin whitening and / or anti-wrinkle.
일 양태로, 본 발명은 상기 미도드린을 포함하는 피부 미백 및/또는 주름개선용 식품 조성물을 제공한다.In one aspect, the present invention provides a food composition for skin whitening and / or anti-wrinkle comprising mididorin.
다른 측면에서 본 발명은 미도드린을 유효성분으로 포함하는 피부 장벽 강화 및/또는, 피부 염증 예방 및/또는 개선용 화장료 조성물을 제공한다.In another aspect, the present invention provides a cosmetic composition for strengthening and / or preventing skin inflammation and / or improving skin barrier including midoderin as an active ingredient.
상기 미도드린은 상기 피부 장벽 강화 및/또는, 피부 염증 예방 및/또는 개선용 화장료 조성물에 1 내지 10000μM 농도로 포함될 수 있다.The middorin may be included in a concentration of 1 to 10000 μM in the cosmetic composition for strengthening and / or preventing skin inflammation and / or improving skin barrier.
상기 피부 염증은 알러지성 피부염, 접촉성 피부염 또는 아토피 피부염일 수 있으나, 반드시 이로 제한되는 것은 아니다.The skin inflammation may be allergic dermatitis, contact dermatitis or atopic dermatitis, but is not necessarily limited thereto.
상기 피부 장벽 강화 또는, 피부 염증 예방 또는 개선용 화장료 조성물은 PPAR-δ(Peroxisome proliferator-activated receptor-delta) 또는 AMPK(5' AMP-activated protein kinase)의 발현을 증가시킬 수 있다.The cosmetic composition for strengthening or preventing or improving skin barrier may increase expression of PPAR-δ (Peroxisome proliferator-activated receptor-delta) or AMPK (5 'AMP-activated protein kinase).
상기 피부 장벽 강화 및/또는, 피부 염증 예방 및/또는 개선용 화장료 조성물은 TNF-α(Tumor necrosis factor-alpha)의 발현을 감소시킬 수 있다.The skin barrier strengthening and / or skin inflammation prevention and / or improvement cosmetic composition may reduce the expression of Tumor necrosis factor-alpha (TNF-α).
상기 피부 장벽 강화 및/또는, 피부 염증 예방 및/또는 개선용 화장료 조성물은 인볼루크린(involucrin), 케라틴(keratin) 및/또는 디펜신(defensin)의 발현을 증가시킬 수 있다.The cosmetic composition for strengthening and / or preventing skin inflammation and / or improving skin barrier may increase expression of involucrin, keratin and / or defensin.
또 다른 측면에서, 본 발명은 미도드린(midodrine)을 유효성분으로 포함하는 염증성 피부질환 치료 또는 예방용 약학적 조성물을 제공한다.In another aspect, the present invention provides a pharmaceutical composition for treating or preventing inflammatory skin diseases, including midodrine as an active ingredient.
상기 염증성 피부질환은 아토피성 피부염, 지루성 피부염, 접촉성 피부염, 홍반성 루프스 및 구진상 두드러기로 이루어진 군에서 선택된 하나 이상일 수 있으나, 반드시 이로 제한되는 것은 아니다.The inflammatory skin disease may be one or more selected from the group consisting of atopic dermatitis, seborrheic dermatitis, contact dermatitis, lupus erythematosus and papular urticaria, but is not necessarily limited thereto.
일 양태에서 본 발명은 미도드린(midodrine)을 포함하는 염증성 피부질환 개선용 식품 조성물을 제공한다.In one aspect, the present invention provides a food composition for improving inflammatory skin disease, including midodrine.
미도드린(midodrine) 화합물은 아마틴(amatine), 프로아마틴(proamatine), 구트론(gutron) 등의 상표명으로 판매되고, 그 IUPAC 명은 (RS)- N-[2-(2,5-디메톡시페닐)-2-히드록시에틸]글리신아미드 ((RS)- N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]glycinamide)으로서, 하기 화학식 I로 표시된다.Midodrine compounds are sold under trade names such as amatein, proamatine, gutron, and the like. The IUPAC name is (RS) -N- [2- (2,5-dime Methoxyphenyl) -2-hydroxyethyl] glycinamide ((RS) -N- [2- (2,5-dimethoxyphenyl) -2-hydroxyethyl] glycinamide), represented by the following formula (I).
[화학식 I][Formula I]
미도드린은 α1-아드레날린 수용체(α1-AR) 효능제(agonist)이다. 본 발명은 α1-아드레날린 수용체의 한 종류인 미도드린을 피부 미백 또는 주름 개선 용도로 사용하였다. Midodrine is an α1-adrenergic receptor (α1-AR) agonist. In the present invention, midodrin, a type of α1-adrenergic receptor, was used for skin whitening or wrinkle improvement.
미도드린은 생체 내에서 활성대사산물인 데스글리미도드린(desglymidodrine)으로 변화되어 α1-아드레날린 수용체를 활성화시키고, 이어서 AMPK 활성화, PPAR-δ, 또는 PGC-1α의 발현을 유도할 수 있다.Midoderin can be transformed in vivo into an active metabolite, desglymidodrine, to activate the α1-adrenergic receptor and then induce the expression of AMPK activation, PPAR-δ, or PGC-1α.
본 발명에서 용어 "피부 미백"이란 피부의 색소 침착을 완화시키는 모든 수단을 의미한다. 예를 들면, 멜라닌 색소를 감소시키는 수단을 말한다. As used herein, the term "skin whitening" means all means to relieve pigmentation of the skin. For example, it means a means for reducing melanin pigment.
본 발명의 화장료 조성물은 티로시나아제(tyrosinase) 활성을 억제하는 기능을 수행하여 피부 미백 효과를 나타낼 수 있다.The cosmetic composition of the present invention may exhibit a skin whitening effect by performing a function of inhibiting tyrosinase activity.
티로시나아제는 피부 색소인 멜라닌(melanin) 합성의 초기 단계에서 촉매 기능을 수행하는 핵심적인 효소이다. 따라서, 티로시나아제의 활성을 억제함으로써 멜라닌 합성을 저해하고 결과적으로 피부 미백 효과를 나타낼 수 있다.Tyrosinase is a key enzyme in the early stages of the synthesis of the skin pigment melanin. Thus, by inhibiting the activity of tyrosinase, it is possible to inhibit melanin synthesis and consequently exhibit a skin lightening effect.
본 발명에서 용어 "주름"이란, 피부가 쇠하여 생긴 잔줄을 의미하는데, 유전자에 의한 원인, 피부 진피에 존재하는 콜라겐과 엘라스틴의 감소, 외부환경 등에 의해 유발될 수 있다.In the present invention, the term "wrinkle" refers to the fine lines produced by the skin, can be caused by the cause of the gene, the reduction of collagen and elastin in the dermis of the skin, external environment and the like.
본 발명에서 용어 "주름 개선"이란, 피부에 주름이 생성되는 것을 억제 또는 저해하거나, 이미 생성된 주름을 완화시키는 것을 말한다.As used herein, the term "improving wrinkles" refers to inhibiting or inhibiting the formation of wrinkles on the skin or to alleviating wrinkles already produced.
본 발명의 화장료 조성물은 엘라스타아제(elastase) 활성을 억제하는 기능을 수행하여 주름을 방지하거나 개선하는 기능을 수행할 수 있다.The cosmetic composition of the present invention may perform a function of inhibiting elastase activity to prevent or improve wrinkles.
엘라스타아제는 피부 탄력을 유지시켜주는 단백질 성분인 엘라스틴(elastin)을 분해하여 주름살 생성에 관여하는 효소이다. 따라서 엘라스타아제의 활성을 억제함으로써 주름 생성을 억제할 수 있다.Elastase is an enzyme involved in the production of wrinkles by breaking down elastin, a protein component that maintains skin elasticity. Therefore, wrinkles can be suppressed by inhibiting the activity of elastase.
또한, 본 발명의 화장료 조성물은 콜라게나아제(collagenase) 활성을 억제하는 기능을 수행하여 주름을 방지하거나 개선하는 기능을 수행할 수 있다. In addition, the cosmetic composition of the present invention may perform a function of inhibiting collagenase (collagenase) activity to prevent or improve wrinkles.
콜라겐(collagen)은 힘줄, 인대, 혈관 또는 피부에 많은 양으로 존재하는 구조 단백질로서 엘라스틴과 더불어 피부 탄력 유지에 관여하고, 노화가 진행되면서 피부 내 콜라겐의 함량이 감소하면 주름살이 생기게 된다. 콜라게나아제는 콜라겐을 분해하는 효소로서 이의 작용을 억제하면 콜라겐의 감소를 최소화할 수 있다.Collagen (collagen) is a structural protein present in large amounts in tendons, ligaments, blood vessels or skin and is involved in maintaining skin elasticity along with elastin, and wrinkles occur when the collagen content in the skin decreases as aging progresses. Collagenase is an enzyme that breaks down collagen. Inhibiting its action can minimize collagen reduction.
본 발명의 화장료 조성물은 피부 장벽 강화하거나 그리고/또는, 피부 염증을 예방 및/또는 개선하는 기능을 수행할 수 있다.The cosmetic composition of the present invention may perform a function of strengthening the skin barrier and / or preventing and / or ameliorating skin inflammation.
본 발명에서 용어 "피부 장벽" 이란 피부 가장 바깥층인 표피의 상부층으로 각질형성세포로 이루어진 각질층을 의미한다. 독성 물질이나 미생물, 기계적 자극, 자외선에 대해 가장 중요한 일차방어선이며, 피부를 통한 전해질이나 수분 손실을 억제하여 피부가 정상적인 기능을 수행할 수 있는 환경을 제공하는 기능을 한다.As used herein, the term "skin barrier" refers to a stratum corneum consisting of keratinocytes as the upper layer of the epidermis, the outermost layer of skin. It is the most important primary line of defense against toxic substances, microorganisms, mechanical stimuli and UV rays, and it provides the environment for the skin to perform its normal functions by suppressing electrolyte or moisture loss through the skin.
본 발명에서 용어 "피부 장벽 강화"란 피부의 가장 외각에 위치하는 각질층의 장벽 기능을 강화하는 것으로, 인볼루크린(involucrin) 케라틴(keratin) 및/또는 디펜신(defensin)의 발현을 증가시킴으로써 피부 장벽의 기능을 강화하는 것을 의미한다.The term "strengthening the skin barrier" in the present invention is to strengthen the barrier function of the outermost stratum corneum, the skin by increasing the expression of involucrin keratin and / or defensin (skin) Means to strengthen the barrier function.
케라틴과 인볼루크린은 피부세포를 이루는 단백질로서, 각각 각질세포의 분화 초기와 후기에 생산되는 중요한 분화 생체 표지 인자이다.Keratin and involuclin are proteins that make up skin cells, and are important differentiating biomarkers that are produced early and late in differentiation of keratinocytes, respectively.
구체적으로, 각질형성세포 분화가 진행되면 세포막의 안쪽에서 인볼루크린 등의 구조단백질을 트랜스클루타미아제(transglutamiase)가 결합시켜 물에 녹지 않는 단단한 구조물인 각질세포막(cornified cell envelope)을 형성하게 된다. 이러한 각질형성세포 분화가 어떤 외부적 영향으로 인해 비정상적으로 일어나게 되면 피부 장벽 기능에 이상을 초래하고 피부의 건조를 야기하여 결과적으로 아토피 등과 같은 만성피부질환이 발생하는 것으로 알려져 있다.Specifically, as the keratinocyte differentiation progresses, transglutamiase binds structural proteins such as involuclin to the inside of the cell membrane to form a corneal cell envelope, which is a hard structure insoluble in water. . When such keratinocyte differentiation occurs abnormally due to some external influences, it is known to cause abnormalities in skin barrier function and dry skin, resulting in chronic skin diseases such as atopic dermatitis.
디펜신은 피부세포가 분비하는 항세균 작용을 하는 방어물질로서 피부보호의 또 다른 생체 표지 인자이다. 따라서 디펜신의 발현을 증가시키면 피부 감염을 예방하거나 감소시킬 수 있다.Defensin is an antibacterial defense secreted by skin cells and is another biomarker for skin protection. Thus, increasing expression of defensin can prevent or reduce skin infection.
본 발명의 화장료 조성물은 PPAR-δ(Peroxisome proliferator-activated receptor-delta) 또는 AMPK(5' AMP-activated protein kinase)의 발현을 증가시킬 수 있다. The cosmetic composition of the present invention can increase the expression of PPAR-δ (Peroxisome proliferator-activated receptor-delta) or AMPK (5 'AMP-activated protein kinase).
PPAR-δ 및 AMPK는 각각 생체 내 대사를 적절히 유지시키는데 핵심적인 역할을 하는 전사인자와 효소단백질로 알려져 있으며, 염증 감소 등에도 관여할 수 있다. 따라서 PPAR-δ 또는 AMPK의 발현을 증가시킴으로써 피부 염증의 예방 및 개선에 영향을 미칠 수 있다.PPAR-δ and AMPK are known as transcription factors and enzyme proteins that play key roles in maintaining proper metabolism in vivo, and may be involved in inflammation reduction. Thus, by increasing the expression of PPAR-δ or AMPK can affect the prevention and improvement of skin inflammation.
본 발명의 화장료 조성물은 TNF-α의 발현을 감소시킬 수 있다. TNF-α는 염증 상태를 나타내주는 대표적인 생체 표지로서 피부 손상과 그로 인한 세균 침입시 그 발현이 증가할 수 있다.The cosmetic composition of the present invention can reduce the expression of TNF-α. TNF-α is a representative biomarker indicative of inflammatory conditions and can increase its expression upon skin damage and bacterial invasion.
본 발명의 화장료 조성물은 인볼루크린, 케라틴, 디펜신 등의 발현을 증가시킬 수 있다. 이는 앞서 설명한 바와 같이 피부 장벽 강화 기능을 보여주는 것이다.The cosmetic composition of the present invention can increase the expression of involuclin, keratin, defensin and the like. This shows the skin barrier strengthening function as described above.
상기 미도드린은 상기 화장료 조성물에 1 내지 10000μM 농도로 포함될 수 있다. 바람직하게는 1 내지 700μM , 더욱 바람직하게는 1 내지 500μM, 더더욱 바람직하겐느 1 내지 100 μM 농도로 포함될 수 있다. 이를 중량으로 환산하면, 화장료 전체 조성물 100 중량%로 봤을 때 미도드린은 0.000029 내지 29 중량%로 포함될 수 있다.The middorin may be included in the cosmetic composition at a concentration of 1 to 10000 μM. Preferably 1 to 700 μM, more preferably 1 to 500 μM, even more preferably 1 to 100 μM. In terms of weight, the midodrin may be included in an amount of 0.000029 to 29% by weight, based on 100% by weight of the total cosmetic composition.
상기 미도드린 함량이 1 μM 미만인 경우에는 피부 미백, 주름개선, 피부 장벽 강화 및 피부 염증 예방 또는 개선의 효고를 기대하기 어렵다. 10000μM 을 초과하는 경우에는 미도드린 함량 증가에 비하여 효과의 증가가 미미하여 경제적이지 못하다.When the mididorin content is less than 1 μM, it is difficult to expect the effect of skin whitening, wrinkle improvement, skin barrier strengthening and skin inflammation prevention or improvement. If the amount exceeds 10000 μM, the increase in effect is insignificant compared to that of the mididorin content, which is not economical.
본 발명에 따른 화장료 조성물은 용액, 외용연고, 크림, 폼, 영양화장수, 유연화장수, 팩, 유연수, 유액, 메이크업베이스, 에센스, 비누, 액체 세정료, 입욕제, 선 스크린크림, 선오일, 현탁액, 유탁액, 페이스트, 겔, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 패취 및 스프레이로 구성된 군으로부터 선택되는 제형으로 제조할 수 있으나, 이에 제한되는 것은 아니다.The cosmetic composition according to the present invention is a solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, latex, makeup base, essence, soap, liquid cleansing agent, bath, sunscreen cream, sun oil, suspension, Emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays may be prepared in a formulation selected from the group consisting of, but not limited to It is not.
또한, 본 발명의 화장료 조성물은 일반 피부 화장료에 배합되는 화장품학적으로 허용 가능한 담체를 1 종 이상 추가로 포함할 수 있으며, 통상의 성분으로 예를 들면 유분, 물, 계면활성제, 보습제, 저급 알콜, 증점제, 킬레이트제, 색소, 방부제, 향료 등을 적절히 배합할 수 있으나, 이에 제한되는 것은 아니다.In addition, the cosmetic composition of the present invention may further include one or more cosmetically acceptable carriers formulated in general skin cosmetics, and as conventional components, for example, oil, water, surfactants, moisturizers, lower alcohols, Thickeners, chelating agents, pigments, preservatives, flavoring agents, and the like may be appropriately blended, but are not limited thereto.
본 발명의 화장료 조성물에 포함되는 화장품학적으로 허용가능한 담체는 제형에 따라 다양하다.The cosmetically acceptable carrier included in the cosmetic composition of the present invention varies depending on the dosage form.
본 발명의 제형이 연고, 페이스트, 크림 또는 젤인 경우에는, 담체성분으로서 동물성 유, 식물성 유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크, 산화아연 또는 이들의 혼합물이 이용될 수 있다.When the formulation of the present invention is an ointment, paste, cream or gel, the carrier component is animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these may be used.
본 발명의 제형이 파우더 또는 스프레이인 경우에는, 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록사이드, 칼슘 실케이트, 폴리아미드 파우더 또는 이들의 혼합물이 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진제를 포함할 수 있다.If the formulation of the invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or mixtures thereof may be used, in particular in the case of a spray additionally chloro Propellants, such as fluorohydrocarbons, propane / butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는, 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되며, 예컨대 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알콜, 벤질 벤조에이트, 프로필렌글리콜, 1,3-부틸글리콜 오일이 이용될 수 있으며, 특히, 목화씨 오일, 땅콩 오일, 옥수수 배종 오일, 올리브 오일, 피마자 오일 및 참깨 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 이용될 수 있다.When the formulation of the present invention is a solution or emulsion, solvents, solubilizers or emulsions are used as carrier components, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil may be used, in particular cottonseed oil, peanut oil, corn seed oil, olive oil, castor oil and sesame oil, glycerol aliphatic esters, fatty acid esters of polyethylene glycol or sorbitan may be used. have.
본 발명의 제형이 현탁액인 경우에는, 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알콜, 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 present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, micro Crystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
본 발명의 제형이 비누인 경우에는 담체 성분으로서 지방산의 알칼리 금속 염, 지방산 헤미에스테르 염, 지방산단백질 히드롤리제이트, 이세티오네이트, 라놀린 유도체, 지방족 알콜, 식물성 유, 글리세롤, 당 등이 이용될 수 있다.When the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars and the like can be used as carrier components. Can be.
또한, 본 발명의 화장료 조성물은 상기 미도드린에 더하여 피부 미백 또는 피부 주름 개선 기능을 갖는 물질을 1종 이상 추가로 포함할 수 있다.In addition, the cosmetic composition of the present invention may further include at least one substance having a skin whitening or skin wrinkle improvement function in addition to the middorin.
추가적인 미백 또는 주름 개선 성분을 포함하게 되면 본 발명의 조성물의 미백 및 주름 개선 효과는 더욱 증진될 수 있을 것이다. 미백 또는 주름 개선 성분의 추가시에는 복합 사용에 따른 피부 안전성, 제형화의 용이성, 유효성분들의 안정성을 고려할 수 있다.Inclusion of additional whitening or anti-wrinkle ingredients may further enhance the whitening and anti-wrinkle effect of the compositions of the present invention. The addition of a whitening or anti-wrinkle ingredient may take into account the safety of the skin, ease of formulation, and stability of the active ingredients.
본 발명의 일 구체예에서, 상기 미백 및 주름 개선 조성물은 이 기술분야에 공지된 주름 개선 성분으로서, 레티노산, TGF, 동물 태반 유래의 단백질, 베튤린산 및 클로렐라 추출물로 구성되는 군으로부터 선택되는 하나 이상의 주름 개선 성분을 추가로 포함할 수 있다.In one embodiment of the present invention, the whitening and wrinkle improving composition is one selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract as wrinkle improving ingredients known in the art. The above wrinkle improvement component may further be included.
본 발명의 다른 양태로서, 본 발명은 미도드린을 유효성분으로 포함하는 염증성 피부질환 치료 또는 예방용 약학적 조성물을 제공한다. 상기 미도드린 및 조성물 내 미도드린의 함량 등은 상기 화장료 조성물에서 설명한 것과 동일하다.As another aspect of the present invention, the present invention provides a pharmaceutical composition for treating or preventing inflammatory skin diseases, including middorin as an active ingredient. The amount of mididorin and the like in the composition is the same as described in the cosmetic composition.
본 발명에서 "치료"란 본 발명의 조성물을 개체에 투여하여 염증성 피부질환을 회복시키거나 완화시키는 것을 의미한다."Treatment" in the present invention means administering the composition of the present invention to a subject to recover or alleviate inflammatory skin disease.
상기 개체는, 쥐, 가축, 인간 등을 포함하는 포유동물을 제한 없이 포함한다.The subject includes, without limitation, mammals including rats, domestic animals, humans and the like.
본 발명에서 "예방"이란 본 발명의 조성물을 개체에 투여하여 염증성 피부질환을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다.In the present invention, "prevention" means any action that inhibits or delays the development of inflammatory skin diseases by administering a composition of the present invention to a subject.
본 발명의 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 약학적 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.The pharmaceutical compositions of the present invention may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral dosage forms, external preparations, and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형 제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 외용제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, which solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, external preparations. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
바람직하게는, 본 발명의 염증성 피부질환 치료 또는 예방용 약학적 조성물은 연고, 크림 등의 외용제 제형을 가질 수 있으며, 이에 제한되는 것은 아니나, 비경구 투여 중 경피투여, 보다 바람직하기로는 도포에 의한 국부 투여(topical application) 경로로 적용될 수 있다.Preferably, the pharmaceutical composition for treating or preventing inflammatory skin diseases of the present invention may have a topical formulation such as ointment, cream, etc., but is not limited thereto, transdermal administration during parenteral administration, more preferably by application It can be applied by topical application route.
본 발명의 또 다른 양태로서, 본 발명은 미도드린을 포함하는 피부 미백 또는 주름개선용 식품 조성물을 제공한다.As another aspect of the present invention, the present invention provides a food composition for skin whitening or wrinkle improvement comprising middorin.
또 다른 양태로서, 본 발명은 미도드린을 포함하는 염증성 피부질환 개선용 식품 조성물을 제공한다.In still another aspect, the present invention provides a food composition for improving inflammatory skin disease, including middorin.
본 발명의 미도드린을 포함하는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제 등이 있으며, 이에 제한되는 것은 아니다.Examples of the food containing midodrin of the present invention include various foods, beverages, gums, teas, vitamin complexes, and the like, but are not limited thereto.
본 발명의 식품 조성물에 있어서, 미도드린의 함량은 전체 조성물 중량에 대하여 0.000001 중량％ 내지 20 중량％일 수 있으며, 보다 바람직하게는 0.001 내지 10 중량％, 가장 바람직하게는 0.1 중량％ 내지 10 중량％일 수 있다.In the food composition of the present invention, the content of middorin may be 0.000001% to 20% by weight, more preferably 0.001 to 10% by weight, most preferably 0.1 to 10% by weight based on the total weight of the composition. Can be.
본 발명의 피부 미백 및 주름개선용 식품이 음료일 경우, 지시된 비율로 필수 성분으로서 미도드린을 함유하는 외에는 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 당 알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.When the food for skin whitening and wrinkle improvement of the present invention is a beverage, there are no special limitations on the other ingredients other than those containing mididorin as essential ingredients at the indicated ratios, and various flavors or natural carbohydrates are added as in general drinks. It may contain as a component. 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 conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, erythritol. Natural flavors (tautin, and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavoring agents other than those mentioned above.The ratio of the natural carbohydrate is generally about 100 ml of the composition of the present invention. 1 to 20 g, preferably about 5 to 12 g.
상기 외에 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등 의 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. 그밖에 본 발명의 식품 조성물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain a fruit flesh for producing natural fruit juice and fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 또 다른 양태로서, 본 발명은 미도드린을 유효성분으로 포함하는 화장료 조성물을 개체의 피부에 도포하는 단계를 포함하는, 피부 미백 방법 및/또는 주름을 예방 및/또는 개선하는 방법을 제공한다.As another aspect of the present invention, the present invention provides a method for preventing and / or ameliorating skin whitening and / or improving wrinkles, comprising applying a cosmetic composition comprising midoderine as an active ingredient to the skin of an individual. do.
또 다른 양태로서, 본 발명은 미도드린을 유효성분으로 포함하는 화장료 조성물을 개체의 피부에 도포하는 단계를 포함하는, 염증성 피부질환을 예방 및/또는 개선하는 방법을 제공한다.In another aspect, the present invention provides a method for preventing and / or ameliorating an inflammatory skin disease, comprising applying a cosmetic composition comprising midoderine as an active ingredient to the skin of an individual.
미도드린을 유효성분으로 포함하는 화장료 조성물은 상기에서 설명한 바와 같다.Cosmetic composition containing middorin as an active ingredient is as described above.
상기 "도포"는 임의의 적절한 방법으로 개체의 피부에 본 발명에 따른 조성물을 접촉시키는 것을 의미하며, 이를 통해 해당 조성물을 피부 내부로 흡수시키는 것을 목적으로 한다.The term "application" means contacting the composition of the present invention with the skin of an individual in any suitable manner, through which the composition is intended to be absorbed into the skin.
상기 "예방"이란 본 발명에 따른 조성물의 도포로 피부의 색소 침작을 방지하는 모든 행위, 그리고/또는 피부의 주름 발생을 억제 또는 지연시키는 모든 행위, 그리고/또는 피부 염증을 억제, 지연 또는 완화시키는 모든 행위를 말한다. The term "prevention" means any action that prevents pigmentation of the skin with the application of a composition according to the invention, and / or any action that inhibits or delays the occurrence of wrinkles on the skin, and / or inhibits, delays or alleviates skin inflammation. Say all the acts.
본 발명에서 용어, "개선"은 본 발명에 따른 조성물의 도포로 피부에서 색소 침착이 잘 일어나지 않거나, 그리고/또는 피부의 주름 상태가 호전되거나 이롭게 변경되거나, 그리고/또는 피부 장벽의 기능이 이전보다 강해지고 피부 염증이 호전되거나 염증 발생이 잘 일어나지 않는 모든 행위를 말한다.As used herein, the term "improvement" means that pigmentation does not occur well in the skin with the application of a composition according to the invention, and / or the wrinkles of the skin are improved or advantageously altered, and / or the function of the skin barrier is greater than before. It is any activity that is stronger and does not improve or cause inflammation of the skin.
본 발명에 따른 미도드린을 유효성분으로 포함하는 화장료 조성물은 미백 효과 및 주름개선 효과를 제공한다. 또한 본 발명의 화장료 조성물은 피부 장벽을 보호하고피부 염증 예방 및 개선 기능을 제공한다. 또한 미도드린을 유효성분으로 포함하는 약제학적 조성물은 피부 염증 예방 또는 치료에 우수한 효과를 나타낸다.The cosmetic composition comprising midodorin according to the present invention as an active ingredient provides a whitening effect and an anti-wrinkle effect. In addition, the cosmetic composition of the present invention protects the skin barrier and provides a function of preventing and improving skin inflammation. In addition, the pharmaceutical composition comprising midodrin as an active ingredient shows an excellent effect on the prevention or treatment of skin inflammation.
도 1은 실시예 2에 따른 세포생존율 시험결과를 나타낸 것이다.
도 2는 실시예 3에 따른 전체 PC-PCR 분석결과를 나타낸 것이다.
도 3 내지 6은 실시예 3에 따른 케라틴(Keratin), 인볼루클린(Involuclin), 디펜신(Defensin), TNF-α 각각에 대한 미도드린 처리에 따른 β-Actin mRNA 에 대한 상대적인 발현량을 비교 분석한 그래프이다.
도 7 은 실시예 4에 따른 PPAR-δ 의 미도드린 처리에 따른 웨스턴 블랏 결과이다.
도 8은 실시예 4에 따른 AMPKα1의 미도드린 처리에 따른 웨스턴 블랏 결과이다.
도 9는 실시예 5에 따른 티로시나아제의 활성 억제율을 나타낸 그래프이다.
도 10은 실시예 6에 따른 엘라스타아제의 활성 억제율을 나타낸 그래프이다.
도 11은 실시예 7에 따른 콜라게나아제의 활성 억제율을 나타낸 그래프이다.Figure 1 shows the cell viability test results according to Example 2.
Figure 2 shows the overall PC-PCR analysis results according to Example 3.
3 to 6 compare the relative expression levels for β-Actin mRNA according to midodrin treatment for keratin, Involuclin, Defensin, and TNF-α according to Example 3, respectively. This is a graph analyzed.
7 is a western blot result of midodrin treatment of PPAR-δ according to Example 4. FIG.
8 is a Western blot result of the midodrin treatment of AMPKα1 according to Example 4.
9 is a graph showing the activity inhibition rate of tyrosinase according to Example 5.
10 is a graph showing the activity inhibition rate of elastase according to Example 6.
11 is a graph showing the activity inhibition rate of collagenase according to Example 7.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시하나, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 이 기술분야의 통상의 기술자에게 있어서 명백한 것이며, 이러한 변형 및 수정이 첨부된 특허청구범위에 속하는 것도 당연한 것이다.Hereinafter, preferred examples are provided to aid the understanding of the present invention, but the following examples are merely illustrative of the present invention, and various changes and modifications can be made within the scope and spirit of the present invention. It is obvious to the skilled person, and it is natural that such variations and modifications fall within the scope of the appended claims.
실시예 1: 피부세포(HaCaT)의 배양Example 1 Culture of Skin Cells (HaCaT)
96 well 배양 접시에 세포를 분주한 뒤 10% FBS 및 1% 항생제 함유 배지(DMEM)로써 80% 정도 세포밀집도(cell confluence)를 형성할 때까지 자라게 한 뒤 1% FBS 함유 배지로 배지를 갈아주고 약물(미도드린, SDS, DNCB)을 처리한 후 24시간 뒤에 실험을 진행하였다. 모든 배양과정은 무균 실험대(클린벤치)에서 진행하고 세포의 배양은 37℃의 CO2 배양기 안에서 하였다.Dispense the cells in a 96 well culture dish, grow them to about 80% cell confluence with 10% FBS and 1% antibiotic-containing medium (DMEM), and then change the medium with 1% FBS-containing medium. The experiment was performed 24 hours after treatment with drugs (midodrine, SDS, DNCB). All cultures were carried out on a sterile bench (clean bench) and the cells were cultured in a 37 ° C. CO 2 incubator.
실시예 2: 세포 생존율 시험 (Cell viability test)Example 2: Cell viability test
HaCaT 세포주에 처리하는 SDS(sodium dodecyl sulfate)와 DNCB (2,4-Dinitrochlorobenzene)의 적정 농도를 결정하기 위해 96 웰 배양 접시에 세포를 웰당 5000개씩 분주하고 24시간 뒤에 SDS와 DNCB를 각각 5~2000μM, 그리고 0.5~400μM로 농도별 처리한 다음 24시간 후 CCk-8 시약을 각 웰 당 10㎕ 첨가하고 2시간이 지난 다음 450nm의 파장에서 흡광도를 ELISA reader기를 이용하여 측정하였다.To determine the optimal concentrations of sodium dodecyl sulfate (SDS) and DNCB (2,4-Dinitrochlorobenzene) treated in HaCaT cell lines, 5000 cells per well were dispensed in 96-well culture dishes and 5 to 2000 μM of SDS and DNCB, respectively, after 24 hours. And, after 24 hours after treatment by concentration of 0.5 ~ 400μM 10kL CCk-8 reagent was added to each well and after 2 hours, the absorbance at 450nm wavelength was measured using an ELISA reader.
참고로, SDS는 계면활성제로서 피부에 장기간 접촉 시 피부 장벽을 손상시켜 피부를 거칠게 하고 심하면 피부염을 유발할 수 있는 물질이다. DNCB는 일반적으로 접촉성 피부염과 아토피 피부염을 유발한다고 알려진 유기용매이다.For reference, as a surfactant, SDS is a substance that can damage the skin barrier and prolong the dermatitis when severely contacted with the skin. DNCB is an organic solvent generally known to cause contact dermatitis and atopic dermatitis.
상기 방법에 따른 측정 결과, 실시예 2에 따른 세포생존율 시험결과를 도 1에 나타내었다. 세포 생존율을 50% 감소시키는 농도를 적정 처리 농도로 결정하였고 그 농도는 SDS는 50μM, 그리고 DNCB는 10μM 이었다. 또한, 미도드린의 경우 적정 처리 농도를 30μM로 결정하였다.As a result of the measurement according to the above method, the cell viability test results according to Example 2 are shown in FIG. 1. Concentrations that reduced cell viability by 50% were determined as the appropriate treatment concentrations: 50 μM SDS and 10 μM DNCB. In addition, in the case of middorin, an appropriate treatment concentration was determined to be 30 μM.
실시예 3: mRNA 발현량 측정을 위한 역전사 중합효소 연쇄반응(Reverse transcription polymerase chain reaction, RT-PCR) 분석Example 3: Reverse transcription polymerase chain reaction (RT-PCR) analysis for mRNA expression level measurement
DNCB 10μM, SDS 50μM 농도로 각각 처리된 피부세포(HaCaT)를 이용하여 알파 교감신경 자극제인 미도드린의 처리에 따른, 케라틴 1, 인볼루클린, 디펜신, TNF-α의 mRNA 발현 정도를 RT-PCR을 통하여 분석하였으며, 하우스키핑 유전자(Housekeeping Gene)는 β-Actin으로 하였다.MRNA levels of
상기 조건에 따른 RT-PCR 결과를 도 2에 나타내었고, β-Actin mRNA 발현량에 따른 상대적인 발현량을 비교 분석한 그래프를 케라틴, 인볼루클린, 디펜신 및 TNF-α, PPAR-δ 및 AMPKα1에 대해 각각 도 3 내지 도 6에 나타내었다.The results of RT-PCR according to the above conditions are shown in FIG. 2, and the graphs comparing and analyzing the relative expression levels according to the β-Actin mRNA expression amount are keratin, involuclin, defensin and TNF-α, PPAR-δ, and AMPKα1. 3 to 6, respectively.
구체적인 방법으로는, 상기 피부세포들을 각 처치군 당 3개씩 6웰 배양 접시에 분주하고 미도드린 30μM을 처리한 뒤 mRNA 추출 시약인 TriZol을 200㎕씩 넣고 mRNA를 추출후 260nm 파장에서 RNA 정량을 한 다음 cDNA를 합성하고 이를 사용하여 RT-PCR을 진행하였다.As a specific method, three skin cells were dispensed into 6-well culture dishes for each treatment group, treated with 30 μM of mididorin, 200 μl of triZol, an mRNA extraction reagent, and mRNA was extracted. Then cDNA was synthesized and used for RT-PCR.
아래의 표 1에 PCR 반응 조건 및 프라이머 정보를 정리하였다.Table 1 below summarizes PCR reaction conditions and primer information.
(서열번호 1)cccttctttcgaggtcttgg
(SEQ ID NO 1)
(서열번호 2)tgctggaaggtaggcacaag
(SEQ ID NO: 2)
(서열번호 3)cacctagaggagcaggaggg
(SEQ ID NO: 3)
(서열번호 4)caggtgctttggctgtccta
(SEQ ID NO: 4)
(서열번호 5)tgagatggcctcaggtggta
(SEQ ID NO: 5)
(서열번호 6)agctcacttgcagcacttgg
(SEQ ID NO: 6)
(서열번호 7)ccctcaacctcttctggctc
(SEQ ID NO: 7)
(서열번호 8)agctgtaggccccagtgagt
(SEQ ID NO: 8)
(서열번호9)gcttggtcacttcgtggcta
(SEQ ID NO: 9)
(서열번호 10)caaaccgcttccaactcaaa
(SEQ ID NO: 10)
도 3 내지 도 6에 따르면, 케라틴은 SDS 처리군에서 감소하였지만 미도드린을 처리함으로써 의미 있게 증가하였다(도 3). 인볼루클린의 경우 SDS와 미도드린을 같이 처리한 군에서 유의미하게 증가하였다(도 4). 디펜신의 경우 SDS와 DNCB만 처리한 군보다 미도드린을 같이 처리한 군에서 유의미하게 증가하였다(도 5). According to FIGS. 3-6, keratin decreased in the SDS treated group but significantly increased by the treatment of midodrin (FIG. 3). Involuclin was significantly increased in the group treated with SDS and midodrin (FIG. 4). Defensin was significantly increased in the group treated with middorin as compared to the group treated with SDS and DNCB only (FIG. 5).
또한, TNF-α는 미도드린 처리한 군이 SDS 및 DNCB만 처리한 군보다 의미 있게 mRNA 발현량이 감소하였다. PPAR-δ와 AMPKα1의 경우 DNCB만 처리한 군보다 미도드린 처리한 군에서 mRNA 발현이 의미 있게 증가하였다(도 6).In addition, TNF-α significantly decreased mRNA expression in the midodrin-treated group than the SDS- and DNCB-only group. In the case of PPAR-δ and AMPKα1, mRNA expression was significantly increased in the midodrin-treated group than in the DNCB-only group (FIG. 6).
실시예4: 단백질 발현량 분석을 위한 웨스턴 블랏 분석Example 4 Western Blot Analysis for Protein Expression Analysis
DNCB 10μM 또는 SDS 50μM 농도를 처리한 피부세포(HaCaT)에 동시에 미도드린 30μM과 PPAR-δ 길항제(antagonist)인 GSK0660 50μM을 24시간 동안 처리 후 단백질을 추출하여 Bradford 방법을 사용하여 단백량을 측정 한 뒤 실험 하였다. 추출한 단백질 10 ug을 10% SDS-PAGE(sodium dodecyl sulfate polyacrylamide) 전기영동 후 니트로셀룰로오스 멤브레인에 블랏팅한 다음 5% 스킴 밀크 용액 (0.05% tween20 함유 TBS (TBS-T)에 용해)으로 실온에서 2시간 또는 4℃에서 12시간 이상 블럭킹(blocking)을 한 후 PPARδ, 총(total) AMPK, 그리고 인산화(phosphorylated) AMPK 1차 항체를 2시간 동안 실온에서 결합시킨다. TBS-T로 세척 후 2차 항체를 1시간 동안 실온에서 결합 시킨 뒤 TBS-T 세척을 하고 화학 형광 시약 (chemiluminescent substrate 및 enhancer solutions)을 처리하고 암실에서 x-ray 필름에 감광 시킨 뒤 현상액(developing solution)과 고정액(fixing solution)에 적당한 시간 동안 담가 단백질 발현량을 확인한다.The skin cells (HaCaT) treated with DNCB 10μM or SDS 50μM concentration were simultaneously treated with 30μM midodrin and 50μM GSK0660, a PPAR-δ antagonist, and the protein was extracted using Bradford method. Experiment. 10 ug of the extracted protein was subjected to 10% SDS-PAGE (sodium dodecyl sulfate polyacrylamide) electrophoresis and blotted onto nitrocellulose membrane, followed by 5% skim milk solution (dissolved in TBS (TBS-T) containing 0.05% tween20) at room temperature. PPARδ, total AMPK, and phosphorylated AMPK primary antibodies are bound for 2 hours at room temperature after blocking for at least 12 hours at 4 ° C. After washing with TBS-T, the secondary antibody was bound for 1 hour at room temperature, followed by TBS-T washing, treatment with chemiluminescent substrates and enhancer solutions, and photosensitive in x-ray films in the dark. solution and fixation solution (fixing solution) soak for a suitable time to check the protein expression level.
도 7과 8은 차례대로 미도드린 처리에 따른 PPAR-δ와 인산화AMPK (AMPK의 활성화 형태)의 발현양을 보여주는 웨스턴 블랏 결과를 나타낸 것이다. SDS 또는 DNCB에 미도드린을 병합 처리한 경우 처리한 경우 PPAR-δ의 발현양(도 7)은 두 경우에서 모두 증가 하였고, 인산화 AMPK의 경우 DNCB 처리 시에만 증가 하였다 (도 8). 7 and 8 show Western blot results showing the amount of expression of PPAR-δ and phosphorylated AMPK (an active form of AMPK) following midodrin treatment. In the case of treatment with middrin combined with SDS or DNCB, the expression amount of PPAR-δ was increased in both cases, and the phosphorylated AMPK was increased only in DNCB treatment (FIG. 8).
상기 결과는 피부가 SDS와 DNCB와 같은 유해물질에 노출된 경우 미도드린을 유효성분으로 포함하는 화장품 또는 약물을 사용함으로써 피부 장벽을 보호하고, 세포대사와 염증 감소를 통해 피부보호 또는 피부 염증 예방 및 치료에 효과를 나타낼 수 있음을 의미한다.The results indicate that when the skin is exposed to harmful substances such as SDS and DNCB, it protects the skin barrier by using cosmetics or drugs containing midodrine as an active ingredient, and protects skin or prevents skin inflammation through cell metabolism and inflammation. It can be effective in treatment.
실시예 5: 티로시나아제(Tyrosinase) 활성 억제 효능 시험Example 5: Tyrosinase Activity Inhibition Efficacy Test
0.175 M, pH 6.8 인산나트륨 완충액(sodium phosphate buffer solution)에 기질인 3,4-Dihydroxy-L-phenylalanine (L-DOPA)를 1.5 mM 농도로 녹인 용액 80㎕, 동일한 완충액에 ㎖ 당 320 unit의 농도로 제조한 티로시나아제 용액 20㎕, 및 미도드린이 포함된 시료액 100㎕을 포함하는 혼합용액을 37℃에서 10분 동안 반응시킨 후 microplate reader를 이용하여 490nm 파장에서 흡광도를 측정하였다. 0.175 M, pH 6.8 80 μl solution of 3,4-Dihydroxy-L-phenylalanine (L-DOPA), a substrate in sodium phosphate buffer solution, at a concentration of 1.5 mM, 320 units per ml in the
상기 미도드린이 포함된 시료액은 농도별 티로시나아제 활성 억제 정도를 관찰하기 위하여 10, 30, 50 및 100μM 수용액으로 다양하게 준비하였다. 이때, 공시험액(blank)는 기질과 시료액만 첨가된 군(티로시나아제 용액 대신 버퍼를 20㎕ 첨가함)으로 하고, 대조군은 기질, 티로시나아제 용액만 첨가된 군(시료액 대신 완충액 100㎕ 첨가) 한 것이다.The sample solution containing the midodrin was prepared in a variety of 10, 30, 50 and 100μM aqueous solution in order to observe the degree of inhibition of tyrosinase activity by concentration. In this case, the blank (blank) is the group and the sample solution only added (20 μl of buffer instead of tyrosinase solution), the control group is added to the substrate, tyrosinase solution only (buffer 100 instead of the sample solution) Μl addition).
티로시나아제 억제 활성은 아래의 식 1에 따라 계산하였다.Tyrosinase inhibitory activity was calculated according to
[식 1] [Equation 1]
티로시나아제 활성 억제율(%) = [1 - (시료첨가군의 흡광도/무첨가군의 흡광 % Inhibition of tyrosinase activity = [1-(absorbance of sample addition / absorption of no addition group
도)]×100Degree)] × 100
상기 방법에 따른 분석 결과를 도 9에 나타내었다.Analysis results according to the method are shown in FIG. 9.
도 9에 따르면, 미도드린을 농도별(10 내지 100μM)로 상기 반응액에 첨가하였을 때 농도 의존적으로 티로시나아제의 활성이 감소하는 것으로 나타났다.According to FIG. 9, it was shown that the concentration of tyrosinase activity was reduced depending on concentration when midodrin was added to the reaction solution by concentration (10 to 100 μM).
다시 말해, 미도드린을 유효성분으로 포함하는 화장료 조성물이나 약학적 조성물을 사용할 때 티로시나아제의 활성을 억제하여 미백효과를 나타낼 수 있음을 의미한다.In other words, when using a cosmetic composition or a pharmaceutical composition containing a middorin as an active ingredient, it means that it can exhibit a whitening effect by inhibiting the activity of tyrosinase.
실시예 6: 엘라스타아제(Elastase) 활성 억제 효능 시험Example 6: Elastase Activity Inhibition Efficacy Test
상기 미도드린이 포함된 시료액은 농도별 엘라스타아제 활성 억제 정도를 관찰하기 위하여 10, 30, 50 및 100μM 수용액으로 다양하게 준비하여 0.1 ㎖씩 시험관에 취하였다.The sample solution containing the midodrin was prepared in a variety of 10, 30, 50 and 100μM aqueous solution in order to observe the degree of inhibition of the elastase activity for each concentration was taken in test tubes of 0.1 ml.
50 mM Tris-HCl 완충액 (pH 8.6)에 녹인 elastase pancreatic 용액(Type I：From Porcine Pancreas 유래, 0.6 units/ml) 0.05 ㎖, 기질로 50 mM Tris-HCl 완충액 (pH 8.6)에 녹인 N-succinyl-(L-Ala)3-p-nitroanilide(1mg/ml)을 0.1 ml를 상기 시료액에 넣은 후 37℃에서 30분간 반응시키고 microplate reader를 이용하여410nm 파장에서 흡광도를 측정하였다. 엘라스타아제 활성의 억제는 아래의 식 2에 따라 계산하였다.0.05 ml of elastase pancreatic solution (Type I: From Porcine Pancreas, 0.6 units / ml) dissolved in 50 mM Tris-HCl buffer (pH 8.6), N-succinyl- dissolved in 50 mM Tris-HCl buffer (pH 8.6) as substrate. 0.1 ml of (L-Ala) 3-p-nitroanilide (1 mg / ml) was added to the sample solution, reacted at 37 ° C. for 30 minutes, and absorbance was measured at 410 nm using a microplate reader. Inhibition of elastase activity was calculated according to
[식 2] [Equation 2]
엘라스타아제 활성 억제율(%) = [1 - (시료첨가군의 흡광도/무첨가군의 흡광도)]×100 % Of elastase activity inhibition = [1-(absorbance of sample addition / absorbance of no addition)] × 100
상기 방법에 따른 분석 결과를 도 10에 나타내었다.Analysis results according to the method are shown in FIG. 10.
도 10에 따르면, 미도드린을 농도별(10~100μM)로 반응액에 첨가하였을 때 10μM과 30μM의 저농도에서는 엘라스타아제 활성 억제시키지 못하고 오히려 증가시켰으나, 50μM과 100μM의 고농도에서는 엘라스타아제 활성을 의미 있게 감소시키는 것으로 나타났다.According to FIG. 10, when mididorin was added to the reaction solution at different concentrations (10-100 μM), the elastase activity was not increased at low concentrations of 10 μM and 30 μM, but was increased, but elastase activity was increased at high concentrations of 50 μM and 100 μM. It was found to decrease significantly.
다시 말해, 미도드린을 유효성분으로 포함하는 화장료 조성물이나 약학적 조성물을 사용할 때 티로시나아제의 활성을 억제하여 미백 효과를 나타낼 수 있음을 의미한다.In other words, when using a cosmetic composition or a pharmaceutical composition containing a middorin as an active ingredient, it means that it can exhibit a whitening effect by inhibiting the activity of tyrosinase.
실시예 7: 콜라게나아제(Collagenase) 활성 억제 효능 실험Example 7: Collagenase Activity Inhibition Effect Experiment
0.1M, pH 7.5 tris-HCl 완충용액에 4mM CaCl2를 첨가한 후, 이 용액에 기질인 4-Phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg-OH dihydrate를 0.3mg/㎖ 농도로 용해시킨 기질용액 0.25㎖, 시료액 0.1㎖, 상기 완충용액과 동일한 용액에 0.2mg/㎖ 농도로 제조한 콜라게나아제 효소액 0.15㎖을 혼합한 반응 혼합액을 제조한다. 이때, 상기 시료액은 상기 미도드린이 포함된 시료액은 농도별 콜라게나아제의 활성 억제 정도를 관찰하기 위하여 10, 30, 50 및 100μM 수용액으로 준비하여 0.1㎖씩 시험관에 취하여 준비하였다.4mM CaCl2 was added to 0.1M, pH 7.5 tris-HCl buffer solution, and 4-Phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg-OH dihydrate was dissolved in 0.3mg / ml. A reaction mixture was prepared by mixing 0.25 ml of a substrate solution, 0.1 ml of a sample solution, and 0.15 ml of a collagenase enzyme solution prepared at a concentration of 0.2 mg / ml in the same solution as the buffer solution. At this time, the sample solution was prepared by taking 10 ml, 30, 50 and 100 μM aqueous solution in a test tube to observe the degree of inhibition of collagenase activity by concentration of the sample solution containing the midodrin.
상기 반응 혼합액을 실온에서 20분 동안 반응을 시킨 뒤 6% 시트르산(citric acid) 용액 0.5 ㎖을 첨가하여 반응을 중지시키고, 에틸아세테이트(ethyl acetate) 1.5㎖를 첨가하여 320nm 파장에서 흡광도를 측정하였다.After the reaction mixture was reacted at room temperature for 20 minutes, the reaction was stopped by adding 0.5 ml of 6% citric acid solution, and 1.5 ml of ethyl acetate was added to measure absorbance at 320 nm.
콜라게나아제 활성의 억제는 아래의 식 3에 따라 계산하였다.Inhibition of collagenase activity was calculated according to Equation 3 below.
[식 3][Equation 3]
콜라게나아제 활성 억제율(%) = [1 - (시료첨가군의 흡광도/무첨가군의 흡광 도)]×100Collagenase activity inhibition rate (%) = [1-(absorbance of sample addition / no absorption)] × 100
상기 방법에 따른 분석 결과를 도 11에 나타내었다.The analysis results according to the method are shown in FIG. 11.
도 11에 따르면, 미도드린을 농도별(10~100μM)로 반응액에 첨가하였을 때 농도 의존적으로 콜라게나아제의 활성이 감소함을 확인할 수 있었다.According to Figure 11, it was confirmed that the collagenase activity is reduced depending on the concentration when the midodrin is added to the reaction solution by concentration (10 ~ 100μM).
다시 말해, 미도드린을 유효성분으로 포함하는 화장료 조성물이나 약학적 조성물을 사용할 때 콜라게나아제의 활성을 억제하여 주름예방 및 개선의 효과를 나타낼 수 있음을 의미한다.In other words, when using a cosmetic composition or a pharmaceutical composition containing middorin as an active ingredient, it means that the activity of collagenase can be inhibited and wrinkle prevention and improvement can be exhibited.
이상, 본 발명의 실시예들에 대하여 설명하였으나, 해당 기술 분야에서 통상의 지식을 가진 자라면 특허청구범위에 기재된 본 발명의 사상으로부터 벗어나지않는 범위 내에서, 구성 요소의 부가, 변경, 삭제 또는 추가 등에 의해 본 발명을 다양하게 수정 및 변경시킬 수 있을 것이며, 이 또한 본 발명의 권리범위 내에 포함된다고 할 것이다.As described above, embodiments of the present invention have been described, but those skilled in the art may add, change, delete, or add elements within the scope of the present invention as described in the claims. The present invention may be modified and changed in various ways, etc., which will also be included within the scope of the present invention.
이하, 상기한 실시예의 결과를 근거로 하여, 여러 제조예를 제시한다. 그러나, 이들 제조예는 본 발명을 설명하기 위한 것으로, 본 발명의 제조예에만 국한되지 않는다는 것은 이 기술분야에서 통상의 지식을 가진 자에게 있어서 자명한 것이다Hereinafter, based on the result of the said Example, various manufacture examples are shown. However, these preparation examples are intended to illustrate the present invention, it is obvious to those skilled in the art that the present invention is not limited to the preparation examples of the present invention.
제조예 1: 피부외용제 중 연고Preparation Example 1 Ointment in External Skin Preparation
통상적인 연고 제조 방법에 따라, 하기 표 2에 제시된 함량으로 첨가하고 균일하게 혼합하여 연고를 제조하였다.According to a conventional ointment preparation method, the ointment was prepared by adding in the amounts shown in Table 2 below and mixing uniformly.
제조예 2: 영양크림Preparation Example 2 Nutrition Cream
상기 표 3에 기재된 조성에 따라 통상적인 방법으로 영양크림을 제조하였다.Nutritional cream was prepared in a conventional manner according to the composition described in Table 3.
제조예 3: 건강 식품의 제조Preparation Example 3 Preparation of Health Food
하기 표 4의 성분을 혼합한 후, 30 % 에탄올 100 ㎎을 첨가하여 섭씨 60 ℃에서 건조하여 과립을 형성하였다.After mixing the components of Table 4, 100 mg of 30% ethanol was added and dried at 60 ° C to form granules.
<110> Korea University Research and Business Foundation <120> Composition including midodrine and its uses <130> DHP17-573 <160> 10 <170> KoPatentIn 3.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 1 cccttctttc gaggtcttgg 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 2 tgctggaagg taggcacaag 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 3 cacctagagg agcaggaggg 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 4 caggtgcttt ggctgtccta 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 5 tgagatggcc tcaggtggta 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 6 agctcacttg cagcacttgg 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 7 ccctcaacct cttctggctc 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 8 agctgtaggc cccagtgagt 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 9 gcttggtcac ttcgtggcta 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 10 caaaccgctt ccaactcaaa 20 <110> Korea University Research and Business Foundation <120> Composition including midodrine and its uses <130> DHP17-573 <160> 10 <170> KoPatentIn 3.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 1 cccttctttc gaggtcttgg 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 2 tgctggaagg taggcacaag 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 3 cacctagagg agcaggaggg 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 4 caggtgcttt ggctgtccta 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 5 tgagatggcc tcaggtggta 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 6 agctcacttg cagcacttgg 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 7 ccctcaacct cttctggctc 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 8 agctgtaggc cccagtgagt 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 9 gcttggtcac ttcgtggcta 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 10 caaaccgctt ccaactcaaa 20
Claims (12)
A cosmetic composition for skin whitening or wrinkle improvement comprising midodrine as an active ingredient.
상기 미도드린은 상기 화장료 조성물에 1 내지 10000μM 농도로 포함되는 것을 특징으로 하는 피부 미백 또는 주름개선용 화장료 조성물
The method of claim 1,
The middorin is a cosmetic composition for skin whitening or anti-wrinkle, characterized in that contained in the cosmetic composition in a concentration of 1 to 10000μM
A food composition for skin whitening or wrinkle improvement comprising middorin.
A cosmetic composition for skin barrier reinforcement containing midodrine as an active ingredient.
상기 미도드린은 상기 화장료 조성물에 1 내지 10000μM 농도로 포함되는 것을 특징으로 하는 피부장벽 강화용 화장료 조성물.
The method of claim 4, wherein
The middorin is a cosmetic composition for skin barrier reinforcement, characterized in that contained in the cosmetic composition at a concentration of 1 to 10000μM.
상기 화장료 조성물은 PPAR-δ(Peroxisome proliferator-activated receptor-delta) 또는 AMPK(5' AMP-activated protein kinase)의 발현을 증가시키는 것을 특징으로 하는 피부장벽 강화용 화장료 조성물.
The method of claim 4, wherein
The cosmetic composition is a cosmetic composition for strengthening skin barriers, characterized in that to increase the expression of PPAR-δ (Peroxisome proliferator-activated receptor-delta) or AMPK (5 'AMP-activated protein kinase).
상기 화장료 조성물은 TNF-α(Tumor necrosis factor-alpha)의 발현을 감소시키는 것을 특징으로 하는 피부장벽 강화용 화장료 조성물.
The method of claim 4, wherein
The cosmetic composition is a cosmetic composition for skin barrier reinforcement, characterized in that to reduce the expression of TNF-α (Tumor necrosis factor-alpha).
상기 화장료 조성물은 인볼루크린(involucrin), 케라틴(keratin) 및 디펜신(defensin)의 발현을 증가시키는 것을 특징으로 하는 피부장벽 강화용 화장료 조성물.
The method of claim 4, wherein
The cosmetic composition is a cosmetic composition for strengthening skin barriers, characterized in that to increase the expression of involucrin, keratin (keratin) and defensin (defensin).
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