KR20140089848A - Composition for improving skin wrinkle comprising epifriedelanol - Google Patents
Composition for improving skin wrinkle comprising epifriedelanol Download PDFInfo
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- KR20140089848A KR20140089848A KR1020130001778A KR20130001778A KR20140089848A KR 20140089848 A KR20140089848 A KR 20140089848A KR 1020130001778 A KR1020130001778 A KR 1020130001778A KR 20130001778 A KR20130001778 A KR 20130001778A KR 20140089848 A KR20140089848 A KR 20140089848A
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- South Korea
- Prior art keywords
- skin
- composition
- synthesis
- wrinkles
- laminin
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- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
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Abstract
본 발명은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 개선 또는 피부탄력 증진용 화장료 조성물 및 이를 포함하는 기능성 화장품에 관한 것이다. 또한, 에피프리델라놀을 유효성분으로 포함하는 피부주름 예방 또는 치료용 약학적 조성물 및 피부주름 개선 또는 피부탄력 증진용 식품 조성물에 관한 것이다. 본 발명은 에피프리델라놀을 유효성분으로 포함하는 주름 개선용 조성물에 관한 것으로 에피프리델라놀은 피부세포에서 콜라겐 타입 I 및 라미닌 5의 생합성을 촉진시키며 이들의 분해 효소의 생체 내 억제제인 TIMP-1 및 PAI-1의 생합성을 촉진하는 효능을 나타냄으로 주름 개선 또는 피부탄력 증진에 매우 효과적으로 사용될 수 있다.The present invention relates to a cosmetic composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient and a functional cosmetic composition containing the same. The present invention also relates to a pharmaceutical composition for preventing or treating skin wrinkles containing epipurdelanol as an active ingredient, and a food composition for improving skin wrinkles or skin elasticity. The present invention relates to a composition for improving wrinkles comprising epipurdelanol as an active ingredient, wherein epifredolanol promotes the biosynthesis of collagen type I and laminin 5 in skin cells, and the in vivo inhibitor of these enzymes, TIMP- 1 < / RTI > and PAI-1, and thus can be effectively used for wrinkle improvement or skin elasticity enhancement.
Description
본 발명은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 개선 또는 피부탄력 증진용 화장료 조성물 및 이를 포함하는 기능성 화장품에 관한 것이다. 또한, 에피프리델라놀을 유효성분으로 포함하는 피부주름 예방 또는 치료용 약학적 조성물 및 피부주름 개선 또는 피부탄력 증진용 식품 조성물에 관한 것이다.
The present invention relates to a cosmetic composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient and a functional cosmetic composition containing the same. The present invention also relates to a pharmaceutical composition for preventing or treating skin wrinkles containing epipurdelanol as an active ingredient, and a food composition for improving skin wrinkles or skin elasticity.
피부는 외부 환경으로부터 인체를 보호하고, 내부의 수분 및 유용 성분이 밖으로 유출되는 것을 막아주는 장벽기능, 체온조절, 배설 등 다양한 생리적 기능을 담당하고 있는 중요한 기관이다. 일반적으로 피부 노화는 나이의 증가와 외부 인자들이 주요 원인이 되는 것으로 알려져 있다.Skin is an important body that is responsible for various physiological functions such as barrier function, body temperature control, excretion, etc., which protects the human body from the external environment and prevents the internal moisture and useful components from flowing out. In general, skin aging is known to be a major cause of aging and external factors.
콜라겐은 피부의 섬유아세포에서 생성되는 주요 기질 단백질로써 세포 외 간질에 존재하고, 중요한 기능으로는 피부의 기계적 견고성, 결합조직의 저항력과 조직의 결합력, 세포 접착의 지탱 등이 알려져 있다. 이러한 콜라겐은 연령 및 자외선과 같은 외부 자극에 의해 감소하며, 이는 피부의 주름 형성과 밀접한 연관이 있다고 알려져 있다. 노화가 되면 콜라겐 자체의 합성이 줄어들 뿐 아니라 콜라겐을 포함한 결합조직을 분해하는 MMPs(기질 금속 단백질 분해 효소, matrix metalloproteinase)의 활성이 증가하여 피부조직 내의 콜라겐 분해를 촉진시켜 콜라겐의 함량이 저하되는 원인이 되기도 한다고 알려져 있다. 이러한 MMPs를 억제하는 내재성 억제제인 TIMP (Tissue Inhibitors of Matrix Metalloproteinase)가 존재하는데 MMPs와 TIMP의 활성이 균형을 이루어 적절히 조절이 될 때에 생리적인 조직의 재구성과 항상성이 잘 유지되게 된다.
Collagen is a major substrate protein produced in the fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical durability of the skin, resistance of connective tissues and binding force of tissues, and support of cell adhesion. Such collagen is reduced by external stimuli such as age and ultraviolet rays, which are known to be closely related to the wrinkling of the skin. Aging reduces the synthesis of collagen itself and increases the activity of MMPs (matrix metalloproteinase) that break down connective tissues including collagen, promoting collagen degradation in skin tissues and reducing collagen content Is also known to be. TIMP (Tissue Inhibitors of Matrix Metalloproteinase), which is an inhibitor of MMPs inhibition, is present. When the activity of MMPs and TIMP is appropriately controlled, physiological tissue remodeling and homeostasis are well maintained.
TIMP는 TIMP-1, TIMP-2, TIMP-3, 및 TIMP-4의 4종이 알려져 있는데, 이 중에서 특히 TIMP-1는 MMP-1 및 젤라티나아제(MMP-2, MMP-9) 등의 MMPs의 활성부위에 결합하여 그들의 분해능을 거의 비가역적으로 저해하게 되는 것이다. Among the TIMP-1, TIMP-1, TIMP-2, TIMP-3 and TIMP-4, Lt; RTI ID = 0.0 > degradation < / RTI >
즉, 노화에 따른 피부주름 발생의 중요한 원인이 되는 피부 속 콜라겐은 합성력이 저하되는 것뿐 아니라 분해가 촉진되는데 이 항상성의 주요 기능을 MMPs 및 TIMP가 담당하고 있으며 MMPs는 콜라겐을 포함한 결합조직을 분해함으로써 피부 노화를 촉진시키며 TIMP-1이 이를 저해하는 작용을 수행하게 되는 것이다.
In other words, collagen in the skin, which is an important cause of skin wrinkles due to aging, not only degrades the synthesis ability but also promotes degradation. MMPs and TIMP are responsible for the main function of this homeostasis. MMPs decompose the connective tissue including collagen Which promotes skin aging and TIMP-1 acts to inhibit it.
피부 기저막(skin basement membrane)은 표피세포의 지지 및 부착, 영양물질의 이동, 표피분화의 조절 등에 있어 중요한 역할을 담당하는데 노화에 따라 피부 기저막이 손상되면 기저막의 평평화, 다중화, 단열 등이 일어나서 주름이 발생되며 피부가 쉽게 늘어지거나, 본연의 장벽 기능이 상실되면 외부 환경의 오염물질을 걸려주지 못해 유해물질이 진피까지 침투할 가능성이 높아져 피부가 쉽게 손상될 수 있다. 따라서 손상된 피부 기저막을 회복시키거나 건강한 상태로 유지하려면 먼저 그 구성 성분들이 제대로 유지될 수 있게 해야 한다. 피부 기저막을 이루는 단백질은 다양하게 존재하고 있는데 이중에서도 콜라겐 타입 IV와 라미닌 5(Laminin 5) 등이 피부 노화와 밀접한 관련이 있다는 보고가 있다.
The skin basement membrane plays an important role in the support and adherence of epidermal cells, the movement of nutrients, and the control of epidermal differentiation. When the skin basement membrane is damaged by aging, the basement membrane is flattened, multiplexed, If wrinkles occur and the skin is easily sagged or the barrier function is lost, the possibility of harmful substances penetrating to the dermis increases because the pollutants in the external environment can not be caught and the skin may be easily damaged. Therefore, to restore the damaged basement membrane or to maintain a healthy condition, the components must be properly maintained. There are various proteins that form the skin basement membrane. Collagen type IV and laminin 5 are closely related to skin aging.
라미닌 5는 피부 기저막에 다량으로 존재하고, 피부의 구조 및 기능에 중요한 역할을 하는 것으로 알려져 있는데 라미닌 5가 녹아웃된 마우스는 표피와 진피가 분리되고, 수포를 형성하는 인간 유전성 질환인 표피 수포증과 같은 현상이 나타난다. 이러한 현상으로 보아 라미닌 5는 표피와 진피 접착에 필수적인 것으로 보인다. 표피세포에서 생성되는 활성화 단백질 분해효소인 플라스민(Plasmin)은 유로카이네이즈 플라스미노겐 활성화제(uPA, urokinase-type plasminogen activator)에 의해 활성화 되면서 라미닌 5의 분해에 관여한다. 따라서 프라스민으로 분해된 라미닌 5은 각질세포와의 접착 능력 및 콜라겐과의 친화성이 감소하게 된다. 이 uPA 및 플라스민은 자외선 등에 의해 활성이 증가하게 되는데 이 때문에 자외선 노출에 의한 피부 노화에는 uPA 및 플라스민 활성 증가에 의한 라미닌 5의 분해와 이것에 의한 기적막의 기능 저하가 관여하는 것으로 보고되고 있다. 세린 프로테아제 억제제인 플라스미노겐 활성화제 억제제 타입-1 (PAI-1, Plasminogen activator inhibitor)은 섬유소 분해 시스템의 주요 억제제 중의 하나이다. PAI-1은 플라스미노겐을 플라스민으로 전환하는 효소인 uPA의 주요 생리학적 억제제이다. 따라서 라미닌 5의 분해를 억제하기 위해서는 분해효소인 플라스민의 활성을 억제하거나 플라스민의 활성을 억제하는 효소인 PAI-1의 합성을 촉진시키는 것이 효과적이다.
Laminin 5 is present in large amounts in the basement membrane of the skin and plays an important role in the structure and function of the skin. Laminin 5 knockout mice are distinguished from epidermis and dermis by epidermal blistering, The same phenomenon appears. These results suggest that laminin 5 is essential for epidermal and dermal adhesion. Plasmin, an activated protease produced by epidermal cells, is activated by uracil-type plasminogen activator (uPA) and is involved in degradation of laminin-5. Therefore, laminin 5 degraded by plasmin decreases the ability to adhere to keratinocytes and affinity with collagen. This uPA and plasmin activity is increased by ultraviolet rays. Therefore, it has been reported that degradation of laminin 5 by uPA and plasmin activity is involved in skin aging caused by exposure to ultraviolet rays, and that the action of the membrane is affected by this . Plasminogen activator inhibitor (PAI-1), a serine protease inhibitor, is one of the major inhibitors of the fibrinolysis system. PAI-1 is the major physiological inhibitor of uPA, an enzyme that converts plasminogen to plasmin. Therefore, in order to inhibit the degradation of laminin 5, it is effective to promote the synthesis of PAI-1, an enzyme that inhibits the activity of plasmin, which is a degrading enzyme, or inhibits the activity of plasmin.
따라서, 종래에는 피부 노화와 주름을 개선시키기 위하여 표피-진피의 경계면인 피부 기저막(skin basement membrane)의 구성성분의 생합성을 높이거나 분해를 억제하는 활성 촉진에 초점을 두는 연구가 진행되고 있다.
Therefore, in order to improve skin aging and wrinkles, researches have been carried out in order to enhance the biosynthesis of components of the skin basement membrane, which is the interface between the skin and the dermis, or to promote the activity of inhibiting degradation.
이러한 배경 하에서, 본 발명자들은 에피프리델라놀이 피부세포의 콜라겐 타입 I의 합성 및 TIMP-1의 합성을 촉진할 뿐만 아니라, 라미닌 5의 발현을 증가시키고 PAI-1의 합성을 촉진시키는 효과가 뛰어남을 확인하고 인체에 적용시 뛰어난 주름 개선 효과를 가짐을 확인함으로써 본 발명을 완성하였다.
Under these circumstances, the present inventors not only accelerated the synthesis of collagen type I and the synthesis of TIMP-1 in skin cells of epipurdelor, but also increased the expression of laminin 5 and promoted the synthesis of PAI-1 And has excellent wrinkle-reducing effect when applied to a human body, thereby completing the present invention.
본 발명의 목적은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 개선 또는 피부탄력 증진용 화장료 조성물을 제공하는 것이다.An object of the present invention is to provide a cosmetic composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient.
본 발명의 다른 목적은 상기 조성물을 포함하는 피부주름 개선 또는 피부탄력 증진용 기능성 화장품을 제공하고자 하는 것이다.Another object of the present invention is to provide a functional cosmetic composition for improving skin wrinkles or skin elasticity comprising the composition.
본 발명의 또 다른 목적은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 예방 또는 치료용 약학적 조성물을 제공하고자 하는 것이다.It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating skin wrinkles containing epifriedelanol as an active ingredient.
본 발명의 또 다른 목적은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 개선 또는 피부탄력 증진용 식품 조성물을 제공하는 것이다.
It is still another object of the present invention to provide a food composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient.
상기 목적을 달성하기 위한 하나의 양태로서, 본 발명은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 개선 또는 피부탄력 증진용 화장료 조성물을 제공한다.
In one aspect of the present invention, there is provided a cosmetic composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient.
본 발명의 용어, "에피프리델라놀(epifriedelanol)"은 소수성(hydrophobic) 분자로써 이소프렌(isoprene) 단위에서 유래된 테르펜(terpene) 구조를 가지로 있다. 에피프리델라놀은 순비기나무, 팽나무, 개미취를 비롯한 다양한 식물의 성분으로 함유되어 있다. 에피프리델라놀은 항암 작용과 항염 작용을 하는 것으로 보고되고 있다. 그러나, 피부 조직에서의 주름 발생 또는 피부탄력 관련 연구는 전무하며 충분히 연구되고 있지 않았다.The term "epifriedelanol" of the present invention is a hydrophobic molecule having a terpene structure derived from an isoprene unit. Epipryderanol is contained in various plant components such as pomegranate, cauliflower, and red pepper. Epifredelanol has been reported to have anti-cancer and anti-inflammatory effects. However, there have been no studies on the occurrence of wrinkles or skin elasticity in the skin tissue and it has not been sufficiently studied.
에피프리델라놀의 분자량은 약 429 정도이며, 구조는 하기 화학식 1과 같다.The molecular weight of epipurdelanol is about 429, and the structure thereof is shown in the following formula (1).
에피프리델라놀은 당 분야에서 공지된 각종의 유기 화학적 방법 등을 통하여 화학적으로 합성할 수 있으며, 또한 식물 등으로부터 용이하게 수득할 수 있다. 본 발명에서 사용된 에피프리델라놀은 중국 Yuanshi Biotechnology Co. Ltd.에서 구입하여 사용하였다.
Epifredelanol can be chemically synthesized through various organic chemistry methods known in the art and can be easily obtained from plants and the like. Epifredelanol used in the present invention is commercially available from Yuanshi Biotechnology Co., Ltd. of China. Ltd., Japan.
본 발명에서 에피프리델라놀을 유효성분으로 포함하는 조성물은 바람직하게는 콜라겐 또는 라미닌 5의 합성을 촉진하거나, 분해를 억제하는 효과를 지니는 것일 수 있으며, 구체적으로는 상기 콜라겐 또는 라미닌 5의 분해를 억제하는 것은 TIMP-1(Tissue Inhibitors of Matrix Metalloproteinase-1)의 합성 또는 PAI-1(Plasminogen activator inhibitor-1)의 합성을 촉진하는 것을 통하여 이루어질 수 있다.
In the present invention, the composition comprising epipurdelanol as an active ingredient may preferably have the effect of promoting the synthesis of collagen or laminin 5, or inhibiting degradation, and more specifically, decomposing collagen or laminin 5 Inhibition can be achieved through the synthesis of TIMP-1 (Tissue Inhibitors of Matrix Metalloproteinase-1) or by promoting the synthesis of PAI-1 (Plasminogen activator inhibitor-1).
본 발명의 구체적인 일 실시예에서는 에피프리델라놀이 콜라겐 합성과 라미닌 5의 합성을 촉진하는 것을 확인하였다. 구체적으로, 인간 유래의 섬유아세포에 에피프리델라놀을 포함하는 배양액을 처리한 경우 인체 유래 섬유아세포에서의 콜라겐 합성 촉진 효과 확인 실험에서 일반적으로 콜라겐 합성 능력이 있는 것으로 알려진 비타민 C를 적용한 경우보다 더 적은 농도로 더 우수한 콜라겐 합성 효과를 나타내는 것을 확인하였다(실시예 1 및 표 1). 또한, 인간 유래의 각질형성세포에 에피프리델라놀을 포함하는 배양액을 처리한 후 라미닌 5의 발현이 증가되는 것을 확인하였다(실시예 3 및 표 4). In a specific embodiment of the present invention, it was confirmed that epifredolanol promotes collagen synthesis and laminin 5 synthesis. Specifically, when human-derived fibroblasts were treated with a culture solution containing epiprecillinol, it was found that, in the experiment for confirming collagen synthesis promotion effect in human fibroblasts, It was confirmed that the collagen synthesis effect was more excellent at a low concentration (Example 1 and Table 1). In addition, it was confirmed that the expression of laminin 5 was increased after culturing the human keratinocytes with the culture medium containing epipurelanol (Example 3 and Table 4).
또한, 에피프리델라놀이 콜라겐과 라미닌 5의 분해를 억제하는 것을 확인하였다. 구체적으로, 인간 유래의 각질형성세포에 에피프리델라놀을 포함하는 배양액을 처리한 후 콜라겐 타입 Ⅰ 및 Ⅳ의 분해 억제효과를 가지는 TIMP-1(Tissue Inhibitors of Matrix Metalloproteinase-1)의 합성이 촉진되는 것(실시예 2 및 표 2)과 라미닌 5 분해 억제효과를 가지는 PAI-1(Plasminogen activator inhibitor-1)의 합성이 촉진되는 것을 확인하였다(실시예 4 및 표 5). 따라서, 본 발명의 조성물은 피부주름 개선 또는 피부탄력 증진에 유용히 사용될 수 있다.
In addition, it was confirmed that it inhibited the decomposition of epiprecidolol collagen and laminin 5. Specifically, the synthesis of TIMP-1 (Tissue Inhibitors of Matrix Metalloproteinase-1), which has the effect of inhibiting the collagen type I and IV degradation, is promoted after culturing human-derived keratinocytes with a culture medium containing epipurelanol 1 (Plasminogen activator inhibitor-1) having the effect of inhibiting laminin 5 degradation was accelerated (Example 4 and Table 5). Therefore, the composition of the present invention can be usefully used for improving skin wrinkles or improving skin elasticity.
본 발명의 용어, "피부주름 개선"은, 피부에 주름이 생성되는 것을 억제 또는 저해하거나, 이미 생성된 주름을 완화시키는 것을 의미한다. 또한, 본 발명의 용어, "피부탄력 증진"은, 피부에 물리적인 압박에 대한 회복력, 구체적으로는 콜라겐이나 라미닌 등 피부탄력에 기능하는 구성들에 의한 물리적 피부 반발력을 증진시키는 것을 의미한다.
The term "skin wrinkle improvement" of the present invention means to inhibit or inhibit the generation of wrinkles on the skin, or to alleviate the wrinkles already formed. The term "enhancing skin elasticity " of the present invention means enhancing physical skin repulsion by structures that function to restrain the physical stress on the skin, specifically, skin elasticity such as collagen or laminin.
본 발명의 조성물은 바람직하게는 에피프리델라놀을 전체 조성물 중량에 대하여 1x10-6 내지 10 중량% 포함하는 것일 수 있다. 상기 함량이 1×10-6 중량% 미만이면 피부 세포에서 콜라겐 타입 I의 생성, TIMP-1의 합성, 라미닌 5의 발현 및 PAI-1의 합성을 촉진하는 효과가 저하될 우려가 있고, 10 중량%를 초과하면 용제로의 용해성 등 조성물의 전체적인 가공성이 떨어져, 후술하는 화장품 제형 등 각종 용도로의 사용이 제한될 우려가 있다.
The composition of the present invention may preferably comprise 1 x 10 -6 to 10% by weight, based on the total weight of the composition, of epipurdelanol. If the content is less than 1x10 < -6 > wt%, the effect of promoting collagen type I production, TIMP-1 synthesis, laminin 5 expression and PAI-1 synthesis may be deteriorated. %, The overall processability of the composition, such as solubility in a solvent, is lowered, which may limit the use of the composition for various purposes such as cosmetic formulations to be described later.
본 발명의 피부주름 개선 또는 피부탄력 증진용 조성물은 유효량의 에피프리델라놀을 포함할 때 바람직한 주름 개선 또는 피부탄력 증진 효과를 제공할 수 있다. 본 발명에서 사용하는 용어 "유효량"은, 피부의 주름이 생성되거나 피부 처짐(탄력 감소)을 억제 또는 저해하거나, 이미 생성된 주름을 완화시킬 수 있는 에피프리델라놀의 양을 의미한다. 본 발명의 주름 개선 또는 피부탄력 증진용 조성물에 포함되는 상기 에피프리델라놀의 유효량은 주름 개선 또는 피부탄력 증진용 조성물이 제품화되는 형태, 상기 에피프리델라놀이 피부에 적용되는 방법 및 피부에 머무르는 시간 등에 따라 달라질 것이다. 예컨대, 상기 주름 개선 또는 피부탄력 증진용 조성물이 피부의 주름 생성 또는 피부 처짐에 따른 피부과적 치료를 위한 의약품으로 제품화되는 경우에는 일상적으로 피부에 적용하게 되는 화장품으로 제품화되는 경우에 비해 높은 농도로 에피프리델라놀을 포함할 수 있을 것이다. 화장품으로 제품화되는 경우에 있어서도 유효성분이 단기간 내에 피부에 머무르게 되는 메이크업 제거제, 세정제 등과 같은 워쉬-오프(wash-off) 타입의 화장품의 경우에는 비교적 높은 농도의 에피프리델라놀을 포함할 수 있을 것이다. 반면 유효성분이 장기간 동안 피부에 머무르게 되는 화장수, 유액, 크림, 에센스 등의 리브-온(leave-on) 타입의 화장품의 경우에는 워쉬-오프 타입의 화장품에 비해 낮은 농도의 에피프리델라놀을 포함해도 무방할 것이다.
The composition for improving skin wrinkles or skin elasticity of the present invention can provide a desirable wrinkle improving effect or skin elasticity improving effect when an effective amount of epipuredanol is included. The term "effective amount " as used herein means the amount of epipurdelanol which is capable of inhibiting or inhibiting wrinkles of the skin or deflecting the skin (reducing the elasticity) or alleviating the already formed wrinkles. The effective amount of the epipuredanol contained in the composition for wrinkle improvement or skin elasticity enhancement of the present invention is not particularly limited as long as the composition for wrinkle improvement or skin elasticity enhancement is commercialized, And so on. For example, when the composition for wrinkle improvement or skin elasticity enhancement is commercialized as a medicament for dermatological treatment due to wrinkle formation or skin deflection of the skin, It may contain predelanols. In the case of a cosmetic product, a wash-off type cosmetic such as a make-up remover, a detergent or the like in which the active ingredient remains on the skin in a short period of time may contain a relatively high concentration of epifredolanol. On the other hand, in the case of leave-on type cosmetics such as lotion, cream, essence and the like in which the active ingredient remains on the skin for a long period of time, epipurdelanol is contained at a lower concentration than that of the wash- It will be acceptable.
본 발명의 구체적인 일 실시예에서는, 에피프리델라놀을 외용연고 또는 에센스 제형으로 제조하고(실시예 5), 이를 인간의 피부에 도포하였을 때 우수한 피부주름 개선 효과를 나타냄을 확인하였다(실시예 6-7 및 표 8-9). 특히, 본 발명에서 에피프리델라놀은 낮은 농도 수준으로 즉, 소량으로 적용할 경우에도 우수한 주름 개선 효과를 나타냄을 확인하였다. 이에 따라, 에피프리델라놀은 콜라겐 감소 및 탄력 저하에 관련된 주름 발생이나 피부 기저막의 주요 성분인 콜라겐 타입 Ⅰ 및 Ⅳ와 라미닌 5의 합성 저하 및 분해 촉진에 의한 주름 발생의 억제, 치료 및 개선을 위한 유효성분으로서 이용될 수 있으며 피부 등에 발생한 상처의 치유 효능도 우수하여 상처 치료를 위한 유효성분으로서 이용될 수도 있다. 또한, 에피프리델라놀은 소량으로 포함되어도 우수한 효능이 유지되기 때문에, 의약품 또는 화장품에서 피부 주름, 피부 탄력 저하 또는 피부 노화를 개선 또는 예방하는 유효성분으로서 다양한 제형으로 이용될 수 있어 응용 범위가 넓은 장점을 갖는다.
In a specific example of the present invention, it was confirmed that epifliterolol was prepared into an external ointment or essence formulation (Example 5) and exhibited excellent skin wrinkle-improving effect when it was applied to human skin (Example 6 -7 and Table 8-9). Particularly, it has been confirmed that epifredolanol in the present invention exhibits excellent wrinkle-reducing effect even at a low concentration level, that is, when applied in small amounts. Accordingly, epipuredanolol is used for suppressing, treating and improving wrinkles related to reduction of collagen and elasticity, and reduction of collagen type I and IV and synthesis of laminin 5, which are major components of skin basement membrane, It can be used as an active ingredient and is excellent in the healing efficacy of wounds generated in skin and the like and can be used as an effective ingredient for wound healing. In addition, since epifliteranol is retained in excellent efficacy even when contained in a small amount, it can be used in various formulations as an effective ingredient for improving or preventing skin wrinkles, skin elasticity reduction or skin aging in pharmaceuticals or cosmetics, .
본 발명의 화장료 조성물은 용액, 유탁액, 현탁액, 페이스트, 화장수, 유액, 크림, 로션, 계면활성제-함유 클린징 오일, 비누, 액체 세정료, 입욕제, 에센스, 화장연고, 스프레이, 폼, 젤, 팩, 유연수, 선 스크린, 메이크업 베이스, 파운데이션, 파우더, 메이크업 제거제 및 세정제로 구성되는 군으로부터 선택되는 제형으로 제조될 수 있다. 피부 외용 조성물로서 사용될 때에는 액상, 유상, 크림상, 연고, 스틱상, 팩, 파스타제, 산제 등 외피에 적용될 수 있는 어떠한 제형으로도 이용 가능하다. 본 발명에 따른 화장료 조성물은 바람직하게는 유연화장수, 수렴화장수, 로션, 에센스, 크림, 겔, 팩, 피부, 에센스시트, 하이드로 겔 패치 또는 마스크의 제형일 수 있다.
The cosmetic composition of the present invention may be in the form of a solution, emulsion, suspension, paste, lotion, milky lotion, cream, lotion, surfactant-containing cleansing oil, soap, liquid cleansing agent, bath agent, essence, cosmetic ointment, , A suppository, a sunscreen, a makeup base, a foundation, a powder, a make-up removing agent and a detergent. When used as a composition for external use on the skin, it can be used in any form that can be applied to a skin such as liquid, oil, cream, ointment, stick, pack, pasta, powder. The cosmetic composition according to the present invention may preferably be a formulation of a softening agent, a convergent lotion, a lotion, an essence, a cream, a gel, a pack, a skin, an essence sheet, a hydrogel patch or a mask.
본 발명에 따른 에피프리델라놀을 함유하는 화장료 조성물은 사용 및 취급이 용이하도록 화장학적 또는 약학적으로 허용되는 담체, 희석제, 보조제, 착색제, 안정화제, 착향제, 계면활성제, 유분, 보습제, 알코올, 점증제, 산화방지제, pH 조절제, 자외선 차단제 등을 추가로 함유할 수 있으며, 바람직하게는 물, 계면활성제, 보습제, 저급알코올, 킬레이트제, 살균제, 산화방지제, 방부제, 색소 및 향료로 구성된 군으로부터 선택되는 1종 이상을 추가로 포함하는 것일 수 있다.
The cosmetic composition containing epipurdelanol according to the present invention is a cosmetic or pharmaceutical acceptable carrier, diluent, adjuvant, coloring agent, stabilizer, flavoring agent, surfactant, oil, humectant, alcohol A surfactant, a humectant, a lower alcohol, a chelating agent, a bactericide, an antioxidant, an antiseptic, a coloring matter and a perfume, may be added to the composition of the present invention. , And the like.
또 하나의 양태로서, 본 발명은 상기 조성물을 포함하는 피부주름 개선 또는 피부탄력 증진용 기능성 화장품을 제공한다. In another aspect, the present invention provides a functional cosmetic for improving skin wrinkles or skin elasticity comprising the composition.
본 발명의 기능성 화장품은 콜라겐 합성 또는 라미닌 합성 촉진 효과 등의 피부주름 개선 또는 피부탄력 증진 효과를 나타내고, 그의 제형은 특별히 제한되는 것은 아니나, 예를 들면, 용액, 유탁액, 현탁액, 페이스트, 크림, 로션, 겔, 파우더, 스프레이, 계면활성제-함유 클린징, 오일, 비누, 액체 세정료, 입욕제, 파운데이션, 메이크업베이스, 에센스, 화장수, 폼, 팩, 유연수, 선 스크린 크림, 선오일 등의 제형으로 제조될 수 있고, 바람직하게는 피부외용연고, 유연화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 팩, 에멀젼 또는 오일젤의 제형으로 제조될 수 있다.
The functional cosmetic composition of the present invention exhibits an effect of improving skin wrinkles or improving skin elasticity such as collagen synthesis or promotion of laminin synthesis. The formulation thereof is not particularly limited, and examples thereof include solutions, emulsions, suspensions, Manufactured with formulations such as lotions, gels, powders, sprays, surfactant-containing cleansing, oils, soaps, liquid cleansing agents, bath salts, foundations, makeup bases, essences, lotions, foam, packs, And may preferably be formulated into a skin external ointment, a softening longevity, a nutritional lotion, a nutritional cream, a massage cream, an essence, a pack, an emulsion or an oil gel.
또 하나의 양태로서, 본 발명은 에피프리델라놀을 유효성분으로 포함하는 피부주름 예방 또는 치료용 약학적 조성물 또는 의약외품 조성물을 제공한다. In another aspect, the present invention provides a pharmaceutical composition or a quasi-drug composition for preventing or treating skin wrinkles comprising epipurdelanol as an active ingredient.
본 발명의 조성물은 피부에 주름이 발생할 가능성이 있거나 또는 이미 발생한 개체에게 적용함으로써 피부주름을 예방 또는 치료하는데 활용될 수 있다. The composition of the present invention can be used to prevent or treat wrinkles of skin by applying wrinkles to the skin or by applying it to an already existing body.
본 발명에서 에피프리델라놀을 유효성분으로 포함하는 조성물은 바람직하게는 콜라겐 또는 라미닌 5의 합성을 촉진하거나, 분해를 억제하는 효과를 지니는 것일 수 있으며, 구체적으로는 상기 콜라겐 또는 라미닌 5의 분해를 억제하는 것은 TIMP-1(Tissue Inhibitors of Matrix Metalloproteinase-1)의 합성 또는 PAI-1(Plasminogen activator inhibitor-1)의 합성을 촉진하는 것을 통하여 이루어질 수 있다.In the present invention, the composition comprising epipurdelanol as an active ingredient may preferably have the effect of promoting the synthesis of collagen or laminin 5, or inhibiting degradation, and more specifically, decomposing collagen or laminin 5 Inhibition can be achieved through the synthesis of TIMP-1 (Tissue Inhibitors of Matrix Metalloproteinase-1) or by promoting the synthesis of PAI-1 (Plasminogen activator inhibitor-1).
본 발명의 약학적 또는 의약외품 조성물은 연고, 크림, 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 수용액, 비수성용제, 현탁제 및 유제로 구성되는 군으로부터 선택되는 제형을 가질 수 있으며, 이에 제한되지는 않는다. The pharmaceutical or quasi-drug composition of the present invention is selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aqueous solutions, non-aqueous solvents, suspensions and emulsions And may be formulated, but is not limited thereto.
또한, 본 발명의 약학적 또는 의약외품 조성물은 바람직하게는 약학적으로 허용가능한 부형제를 추가로 포함하는 것일 수 있으며, 상기 약학적으로 허용가능한 부형제는 계면활성제, 유화제, 비누산, 용매, 결합제, 희석제, 활택제, 안정제, 향료, 물, 저급알콜, 증점제, 킬레이트제, 색소, 방부제, 착색제, 보존제, 항생제, 항산화제, 소포제, 항균제, 항재침착제, 효소, 식물 또는 미네랄 오일, 지방, 형광물질, 살진균제, 굴수성 유발물질, 보습제, 방향제, 방향제 담체, 보존제, 단백질, 실리콘, 용해화제, 당 유도체, 일광차단제, 비타민, 식물 추출물 및 왁스로 구성되는 군으로부터 선택되는 1종 이상인 것일 수 있다.
In addition, the pharmaceutical or quasi-drug composition of the present invention may preferably further comprise a pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient may be a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent Preservatives, antibiotics, antioxidants, antifoaming agents, antimicrobial agents, antidotes, enzymes, vegetable or mineral oils, fats, fluorescent materials A preservative, a protein, a silicone, a solubilizing agent, a saccharide derivative, a sunscreen agent, a vitamin, a plant extract, and a wax, in addition to the above-mentioned antioxidant, fungicide, humectant, humectant, fragrance, perfume carrier, preservative,
본 발명의 약학적 조성물은 약학적으로 허용가능한 담체를 추가로 포함할 수 있다. 약학적으로 허용가능한 담체를 포함하는 상기 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제가 포함된다. 비수성용제, 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테로 등이 사용될 수 있다.
The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier. The composition comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, and emulsions. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
본 발명의 약학 조성물의 바람직한 투여량은 대상자의 연령, 성별, 체중, 증상, 질병의 정도, 약물 형태, 투여 경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 약학 조성물은 0.01 내지 1000 mg/일로 투여하는 것이 좋다. 투여는 하루에 한번 할 수도 있고, 수회 나누어 할 수도 있다. 또한, 그 투여량은 연령, 성별, 체중, 질병의 정도, 투여경로 등에 따라서 증감될 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명의 에피프리델라놀은 쥐, 생쥐, 가축, 인간 등의 포유동물에 비경구, 경구 등의 다양한 경로로 투여될 수 있으며, 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내(intracerebroventricular) 주사에 의해 투여될 수 있다.
The preferred dosage of the pharmaceutical composition of the present invention varies depending on the age, sex, weight, symptom, degree of disease, drug form, administration route and period of time of the subject, but can be appropriately selected by those skilled in the art. However, for the desired effect, the pharmaceutical composition of the present invention is preferably administered at 0.01 to 1000 mg / day. The administration can be done once a day, or divided into several times. In addition, the dose may be increased or decreased according to age, sex, weight, degree of disease, route of administration, and the like. Accordingly, the dosage is not limited in any way to the scope of the present invention. The epipurdelanol of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes such as parenteral, oral, and the like, all manner of administration can be expected, Rectal, or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
또 하나의 양태로서, 본 발명은 에피프리델라놀(epifriedelanol)을 유효성분으로 포함하는 피부주름 개선 또는 피부탄력 증진용 식품 조성물을 제공한다.In another aspect, the present invention provides a food composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient.
본 발명의 에피프리델라놀을 포함하는 식품 조성물을 식품 첨가물로 사용할 경우, 상기 조성물 그대로 첨가되거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조 시에는 본 발명의 조성물은 원료에 대하여 0.01 ~ 10 중량%, 바람직하게는 0.05 ~ 1 중량%의 양으로 첨가된다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하로도 사용될 수 있다.When a food composition comprising epipurdelanol according to the present invention is used as a food additive, the composition may be added as it is, or may be used together with other food or food ingredients, and 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 (prevention, health or therapeutic treatment). Generally, in the production of food or beverage, the composition of the present invention is added in an amount of 0.01 to 10% by weight, preferably 0.05 to 1% by weight based on the raw material. However, in the case of long-term ingestion intended for health and hygiene purposes or for the purpose of controlling health, the amount can also be used in the above-mentioned range.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.
본 발명의 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖ 당 일반적으로 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g 이다.The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다. 이들 성분들은 독립적으로 또는 조합하여 사용할 수 있다.
In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention. These components can be used independently or in combination.
또 하나의 양태로서, 본 발명은 피부주름 개선 또는 피부탄력 증진용 화장료 조성물 또는 피부주름 예방 또는 치료용 약학적 조성물의 제조를 위한 에피프리델라놀의 용도 및 유효량의 에피프리델라놀을 개체의 피부에 적용하는 것을 포함하는 피부주름 개선 또는 피부탄력 증진 방법을 제공한다.
In another aspect, the present invention provides a cosmetic composition for improving skin wrinkles or skin elasticity, or the use of epifredelanol for the preparation of a pharmaceutical composition for the prevention or treatment of skin wrinkles, and the use of an effective amount of epipuredanol The present invention provides a method for improving skin wrinkles or improving skin elasticity.
본 발명은 에피프리델라놀을 유효성분으로 포함하는 주름 개선용 조성물에 관한 것으로 에피프리델라놀은 피부세포에서 콜라겐 타입 I 및 라미닌 5의 생합성을 촉진시키며 이들의 분해 효소의 생체 내 억제제인 TIMP-1 및 PAI-1의 생합성을 촉진하는 효능을 나타냄으로 주름 개선에 매우 효과적으로 사용될 수 있다.
The present invention relates to a composition for improving wrinkles comprising epipurdelanol as an active ingredient, wherein epifredolanol promotes the biosynthesis of collagen type I and laminin 5 in skin cells, and the in vivo inhibitor of these enzymes, TIMP- 1 < / RTI > and PAI-1, and thus can be used effectively for improving wrinkles.
이하, 실시예를 통하여 본 발명의 구성 및 효과를 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것일 뿐 본 발명의 범위가 이들 실시예에 의해 제한되는 것은 아니다.
Hereinafter, the constitution and effects of the present invention will be described in more detail through examples. These embodiments are only for illustrating the present invention, and the scope of the present invention is not limited by these embodiments.
실시예Example
1: 인간 유래의 섬유아세포에서의 콜라겐 타입 I의 합성 촉진 효과 확인 1: Confirmation of promoting effect of collagen type I synthesis in human-derived fibroblasts
인간 유래 섬유아세포의 배양액에 에피프리델라놀을 첨가하여, 세포수준에서 콜라겐 합성 촉진 효과를 실험하였다. 사용된 에피프리델라놀은 중국 (Yuanshi Biotechnology Co. Ltd)에서 구입하여 사용하였다. 합성된 콜라겐의 측정은 PICP EIA kit(Procollagen Type I C-Peptide Enzyme Immuno Assay KIT)를 이용하여 정량하였다.The effect of promoting collagen synthesis at the cellular level was examined by adding epipuredanol to the culture medium of human-derived fibroblasts. The epifredolanol used was purchased from China (Yuanshi Biotechnology Co. Ltd). The synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immuno Assay Kit).
실험에서 에피프리델라놀의 최종 농도는 0.1μg/ml, 1μg/ml가 되도록 하였다. 인간 유래의 섬유아세포(human fibroblast)의 배양 배지(DMEM 배지)에 상기 최종 농도가 되도록 에피프리델라놀을 첨가하여 48시간 배양한 후, 배양액을 취하여 PICP EIA 키트로 각 농도에서 콜라겐 합성 정도를 분광광도계를 이용하여 450nm에서 측정하였다.The final concentration of epipurepiranol in the experiment was 0.1 μg / ml, 1 μg / ml. Epifredolanol was added to the human fibroblast culture medium (DMEM medium) for the above-mentioned final concentration and cultured for 48 hours. Then, the culture broth was taken and the degree of collagen synthesis was measured by PICP EIA kit at each concentration And measured at 450 nm using a photometer.
효과의 비교를 위하여 아무것도 첨가하지 않은 섬유아세포의 배양 배지(대조군)와 비타민 C를 최종농도 52.85μg/ml가 되도록 첨가한 시료에 대하여 동일한 방법으로 콜라겐 합성 정도를 측정하였다.For the comparison of the effects, the degree of collagen synthesis was measured in the same manner as in the case of the fibroblast culture medium (control group) to which nothing had been added and the sample to which the vitamin C was added to a final concentration of 52.85 μg / ml.
콜라겐 생성 증가율은 대조군에 대한 상대적인 콜라겐 생성량의 비율로 계산하였으며, 그 결과를 하기 표 1에 정리하였다.The increase rate of collagen production was calculated as a ratio of relative collagen production to the control group, and the results are summarized in Table 1 below.
상기 표 1의 결과에서 볼 수 있듯이, 에피프리델라놀을 처리한 경우에 일반적으로 콜라겐 합성 능력이 있는 것으로 알려진 비타민 C를 처리한 경우보다 1/528 내지 1/52.8의 현저히 적은 농도로 6 내지 7배 이상의 우수한 콜라겐 합성 촉진 효과를 발휘하는 것을 확인할 수 있다.
As can be seen from the results in the above Table 1, it was found that treatment with epifliteranol significantly reduced the concentration of vitamin C from 6 to 7 at a significantly lower concentration of 1/528 to 1 / 52.8 than in the case of vitamin C, It is confirmed that the collagen synthesis promoting effect is superior to the collagen synthesis.
실시예Example
2: 인간 유래의 각질형성세포에서의 2: expression in human-derived keratinocytes
TIMPTIMP
-I의 합성 촉진 효과 확인Confirmation of promoting the synthesis of -I
에피프리델라놀을 인간 유래 각질형성세포 (human HaCaT) 배양액에 첨가하여 세포수준에서 TIMP-1의 합성 촉진 효과를 실험하였다. 합성된 TIMP-1의 측정은 human TIMP-1 ELISA kit(R&D Systems, 미국)를 이용하여 정량하였다.Epipuredanol was added to the culture medium of human-derived keratinocytes (human HaCaT) to examine the effect of promoting the synthesis of TIMP-1 at the cellular level. The synthesized TIMP-1 was quantified using a human TIMP-1 ELISA kit (R & D Systems, USA).
실험에서 에피프리델라놀의 최종 농도는 0.01μg/ml, 0.1μg/ml, 1μg/ml가 되도록 하였다. 에피프리델라놀은 인간 유래의 각질형성세포(human HaCaT)의 배양로 각 농도에서 TIMP-1의 합성 정도를 분광광도계를 이용하여 450 nm에서 측정하였다.The final concentrations of epipurepiranol in the experiment were 0.01 μg / ml, 0.1 μg / ml, and 1 μg / ml. Epipuredanolol was cultured in human-derived keratinocytes (human HaCaT) and the degree of synthesis of TIMP-1 at each concentration was measured at 450 nm using a spectrophotometer.
TIMP-1의 생성 증가율은 대조군에 대한 상대적인 TIMP-1 생성량의 비율로 계산하였으며, 그 결과를 하기 표 2에 정리하였다.The rate of production of TIMP-1 was calculated as a ratio of the amount of TIMP-1 produced relative to the control, and the results are summarized in Table 2 below.
상기 표 2의 결과에서 볼 수 있듯이, 에피프리델라놀을 처리한 경우에 에피프리델라놀을 처리하지 않은 대조군과 비교하여 TIMP-1 합성을 증가시키는 촉진 효과를 보임을 확인하였다. 구체적으로는, 다양한 에피프리델라놀 처리 농도 모두에서 약 10% 이상의 TIMP-1 합성 촉진 효과를 보이는 것을 확인하였다.
As can be seen from the results in Table 2 above, it was confirmed that the treatment with epipuredanol suppressed the increase of TIMP-1 synthesis compared with the control without epipreperanol treatment. Specifically, it was confirmed that about 10% or more of promoting TIMP-1 synthesis was promoted in all the various epipurepiranol treatment concentrations.
실시예Example
3: 인간 유래의 각질형성세포에서의 3: Human-derived keratinocytes
라미닌Laminin
5의 발현 증가 평가 5
에피프리델라놀을 인간 유래 각질형성세포 (human HaCaT) 배양액에 첨가하여 세포수준에서 라미닌 5의 발현 촉진 효과를 실험하였다. Epifredelanol was added to human hCG cultures to stimulate the expression of laminin 5 at the cellular level.
인간 유래의 각질형성세포를 DMEM 배지에서 24시간 배양한 후에 배양된 세포를 인산완충용액(PBS)로 세척하였다. 그 후에 그 세포에 다시 우혈청(Fetal Bovine Serum)이 포함되지 않은 배지에 첨가된 에피프리델라놀을 12시간 동안 각각 0.1 μg/ml, 1 μg/ml의 농도로 교체하여 처리하였다.Human-derived keratinocytes were cultured in DMEM for 24 hours, and the cultured cells were washed with phosphate buffered saline (PBS). Subsequently, the cells were treated with epifredelanol added to a medium containing no Fetal Bovine Serum by replacing with a concentration of 0.1 μg / ml and 1 μg / ml for 12 hours, respectively.
12시간 경과 후 세포를 회수하여 인산완충용액(PBS)로 세척하고, RNA 분리 시약(Tri-reagen, Bibco BRL)을 1ml 첨가하여 총 RNA를 추출한 후 하기의 방법으로 정량적인 역전사 PCR을 수행하였다. 1μg의 총 RNA를 역전사 시스템(Promega사, 미국)을 이용하여 역전사하여 cDNA를 얻었다. 이후 역전사 반응 용액 2 ul를 50mM Kcl, 10mM tri-Hcl(pH 8.3), 5mM MgCl2 및 0.16 mM dNTP의 PCR 반응 완충액 50ul에 섞고, 10 pmol의 프라이머와 1.25 U의 Taq DNA 중합효소를 첨가하여 94°C에서 60초, 60°C에서 120초, 72°C에서 120초의 28 사이클을 수행하였다. 라미닌 5의 서브유닛인 β3 및 GAPDH의 PCR 수행을 위한 프라이머 서열은 하기 표 3과 같다.After 12 hours, the cells were collected, washed with phosphate buffered saline (PBS), and 1 ml of RNA isolation reagent (Tri-reagen, Bibco BRL) was added to extract total RNA. Quantitative reverse transcription PCR was performed by the following method. 1 μg of total RNA was reverse-transcribed using a reverse transcription system (Promega, USA) to obtain cDNA. Then, 2 μl of the reverse reaction solution was mixed with 50 μl of a PCR reaction buffer of 50 mM KCl, 10 mM tri-HCl (pH 8.3), 5 mM MgCl 2 and 0.16 mM dNTP, and 10 pmol of primer and 1.25 U of Taq DNA polymerase were added thereto to obtain 94 28 cycles of 60 seconds at 60 ° C, 120 seconds at 60 ° C, and 120 seconds at 72 ° C were performed. Primer sequences for PCR of β3 and GAPDH, which are subunits of laminin 5, are shown in Table 3 below.
(서열번호 1)5'-TACCCATACGACGTACCAGATTACGCTCAAACAAACTTGAGAGTCAATTTCACCAG-3 '
(SEQ ID NO: 1)
(서열번호 2)5'-CGGGTGGAATTCACTGGCCTCCATGGCCAAGGTCCGGTCTGGACACTG-3 '
(SEQ ID NO: 2)
(서열번호 3)5'-CTGATGCCCCCATGTTCGT-3 '
(SEQ ID NO: 3)
(서열번호 4)5'-TGTGAGGAGGGGAGATTCA-3 '
(SEQ ID NO: 4)
PCR 산물을 아가로스 젤에 전기영동하고 이를 Fluoro-S MultiImager(BioRad)로 분석하였다.PCR products were electrophoresed on agarose gel and analyzed with Fluoro-S MultiImager (BioRad).
분석 결과를 하기 표 4에 종합하여 나타내었다. 에피프리델라놀을 각각 0.1μg/ml, 1μg/ml의 농도로 처리하였을 때 농도에 따른 라미닌 5 서브유닛 β3 유전자의 발현정도(Laminin5β3 mRNA의 양)를 대조군에 대한 상대적인 값(%)으로 하여 표 4에 나타내었다. GAPDH는 유전자 발현변화를 정량적 역전사 PCR 방법으로 확인할 때 내부 지표 유전자(internal control)로 사용하는 유전자로서, GAPDH의 변화에 대한 특정 유전자, 여기에서는 라미닌 5β3의 상대적 양을 나타냄으로써 시료간의 표준화를 이룰 수 있다. The results of the analysis are summarized in Table 4 below. (The amount of Laminin 5? 3 mRNA) of the laminin 5 subunit? 3 gene according to the concentration when the cells were treated at a concentration of 0.1 μg / ml and 1 μg / ml, respectively, Respectively. GAPDH is a gene that is used as an internal control gene when confirming gene expression changes by quantitative reverse transcription PCR. It shows the relative amount of specific gene for the change of GAPDH, here, laminin 5β3, have.
상기 표 4에 나타나는 바와 같이, 에피프리델라놀을 0.1μg/ml, 1μg/ml의 농도로 처리한 경우에 라미닌 5의 발현이 대조군에 비해 통계적으로 유의하게 63%, 92% 증가함을 알 수 있었다.
As shown in Table 4, the expression of laminin 5 was statistically significantly increased by 63% and 92% when treated with 0.1 μg / ml and 1 μg / ml of epifredolanol, respectively, as compared with the control group there was.
실시예Example
4: 인간 유래의 각질형성세포에서의 4: Human-derived keratinocytes
PAIPAI
-1의 합성 촉진 효과 확인-1 synthesis promotion effect
에피프리델라놀을 인간 유래 각질형성세포 (human HaCaT) 배양액에 첨가하여 세포수준에서 PAI-1의 합성 촉진 효과를 실험하였다. 합성된 PAI-1의 측정은 human PAI-1 ELISA kit(R&D Systems, 미국)를 이용하여 정량하였다.Epipuredanol was added to human-derived keratinocytes (human HaCaT) to stimulate the synthesis of PAI-1 at the cellular level. The synthesized PAI-1 was quantified using a human PAI-1 ELISA kit (R & D Systems, USA).
실험에서 에피프리델라놀의 최종 농도는 0.01μg/ml, 0.1μg/ml, 1μg/ml가 되도록 하였다. 에피프리델라놀은 인간 유래의 각질형성세포(human HaCaT)의 배양배지(DMEM 배지)에 첨가하여 24시간 배양한 후 배양액을 취하여 PAI-1 ELISA 키트로 각 농도에서 PAI-1의 합성 정도를 분광광도계를 이용하여 450nm에서 측정하였다.The final concentrations of epipurepiranol in the experiment were 0.01 μg / ml, 0.1 μg / ml, and 1 μg / ml. Epi-Predelanol was added to the culture medium (human HaCaT) culture medium (human HaCaT) for 24 hours, and the culture was taken. The degree of synthesis of PAI-1 was measured spectrophotometrically at each concentration using a PAI-1 ELISA kit And measured at 450 nm using a photometer.
PAI-1의 생성 증가율은 대조군에 대한 상대적인 PAI-1 생성량의 비율로 계산하였으며, 그 결과를 하기 표 5에 정리하였다.The rate of production of PAI-1 was calculated as the ratio of the amount of PAI-1 produced relative to the control, and the results are summarized in Table 5 below.
상기 표 5의 결과에서 볼 수 있듯이, 에피프리델라놀을 처리한 경우에 에피프리델라놀을 처리하지 않은 대조군과 비교하여 PAI-1 합성을 증가시키는 촉진 효과를 보임을 확인하였다. 구체적으로는, 다양한 에피프리델라놀 처리 농도 모두에서 약 40%에 달하는 PAI-1 합성 촉진 효과를 보이는 것을 확인하였다.
As can be seen from the results of Table 5, it was confirmed that the treatment with epipuredanol suppressed the increase of PAI-1 synthesis compared with the control without epifredelanol treatment. Specifically, it was confirmed that PAI-1 synthesis promoting effect of about 40% was attained in all the various epipurepiranol treatment concentrations.
실시예Example
5: 피부 외용연고 및 에센스 제조 5: Skin ointment and essence manufacturing
실시예Example 5-1. 피부 외용연고의 제조 5-1. Manufacture of ointment for external skin
에피프리델라놀을 유효성분으로 포함하는 피부 외용연고를 통상의 방법에 따라 제조하였다(제조예 1). 또한, 유효성분을 제외한 나머지 성분으로 제조한 피부 외용연고를 대조군으로 제조하였다(비교예 1). 상기 제조예 1 및 비교예 1의 조성은 하기 표 6과 같았다.Skin external ointment containing epipurdelanol as an active ingredient was prepared according to a conventional method (Production Example 1). The ointment for external use on the skin prepared from the remaining ingredients except for the active ingredient was prepared as a control (Comparative Example 1). The compositions of Preparation Example 1 and Comparative Example 1 were as shown in Table 6 below.
실시예Example 5-2. 에센스의 제조 5-2. Manufacture of essences
에피프리델라놀을 유효성분으로 포함하는 피부 노화 방지 및 주름개선 화장료 에센스를 통상의 방법에 따라 제조하였다(제조예 2). 또한, 유효성분을 제외한 나머지 성분으로 제조한 에센스를 대조군으로 제조하였다(비교예 2). 상기 제조예 2 및 비교예 2의 조성은 하기 표 7과 같았다.A skin aging-preventing and wrinkle-improving cosmetic essence containing epipurdelanol as an active ingredient was prepared according to a conventional method (Production Example 2). In addition, an essence prepared from the other ingredients except for the active ingredient was prepared as a control (Comparative Example 2). The compositions of Preparation Example 2 and Comparative Example 2 were as shown in Table 7 below.
(1%)Aqueous solution of sodium hyaluronate
(One%)
실시예Example
6: 패널 테스트를 통한 피부주름 개선 효과 확인 6: Confirmation of skin wrinkle improvement effect by panel test
상기 실시예 5-2에서 제조한 에센스(제조예 2 및 비교예 2)를 이용하여 건강한 35세에서 50세의 여성을 대상으로 피부주름 개선 효과를 다음과 같이 시험하였다.Using the essences (Preparation Example 2 and Comparative Example 2) prepared in Example 5-2, the skin wrinkle-improving effect was tested in healthy 35- to 50-year-old women as follows.
35세에서 50세까지의 여성 30명을 15명씩 2개의 군으로 구분하고, 1군은 에피프리델라놀을 0.5% 포함하는 제조예 2의 에센스를, 2군은 비교예 2의 에센스를 안면부에 1일 1회 3개월간 도포하였다. 3개월 후 피부주름의 개선 정도를 피험자의 설문을 통해 평가하였다. 피험자의 설문은 피부주름 개선 및 탄력 증진에 관하여 사용전과 비교하여 개선 없음, 약간의 개선, 상당한 개선의 3단계로 판정하였으며, 그 결과는 하기 표 8에 나타내었다.30 women aged 35 to 50 years were divided into two groups by 15 persons. Group 1 contained the essence of Preparation Example 2 containing 0.5% of epifredolanol and Group 2 contained the essence of Comparative Example 2 to the face Once a day for 3 months. After 3 months, the improvement of skin wrinkles was evaluated by questionnaires. The subjects' questionnaires were judged to be three stages of improvement of wrinkles and improvement of elasticity, no improvement, slight improvement, and considerable improvement as compared with before use, and the results are shown in Table 8 below.
상기 표 8에서 볼 수 있듯이, 에피프리델라놀 0.5%를 포함한 제조예 2의 에센스를 사용한 경우, 사용하지 않은 비교예 2의 에센스를 사용한 경우보다 피부주름 개선 효과가 우수함을 확인할 수 있었다.
As can be seen from the above Table 8, it was confirmed that when the essence of Preparation Example 2 containing 0.5% of epifredolanol was used, the effect of improving skin wrinkles was superior to that of the essence of Comparative Example 2 which was not used.
실시예Example
7: 영상분석을 통한 7: Through image analysis
화장료Cosmetics
에센스의 주름 개선 효과 시험 Wrinkle improvement test of essence
상기 실시예 6을 진행함과 동시에 영상분석을 통하여 제조예 2 및 비교예 2의 주름 개선 효과를 평가하였다. 구체적으로, 상기 실시예 6의 실험이 시작되기 전 눈 밑의 레플리카(replica)를 채취하고(Xantopren, Bayer), 실험이 종료된 직후 레플리카를 눈 밑의 동일한 부위에서 채취하여 영상분석을 하였다. The wrinkle-improving effect of each of Production Example 2 and Comparative Example 2 was evaluated through image analysis while proceeding to Example 6 above. Specifically, the replica under the eye was sampled before the experiment of Example 6 was started (Xantopren, Bayer), and the replica was sampled from the same site under the eye immediately after the experiment was completed.
실험 전 후의 레플리카를 비교하여 피부주름의 2차원적 분석으로 피부주름의 밀도를 측정하였다. 영상 분석에 의한 피부주름 밀도의 감소율은 에센스의 사용전 피부주름 밀도에 대한 사용 후 피부주름 밀도의 비를 평균한 값이며, 상기 측정 결과를 하기 표 9에 정리하였다.The density of skin wrinkles was measured by two-dimensional analysis of skin wrinkles by comparing replicas before and after the experiment. The reduction rate of the skin wrinkle density by image analysis is a value obtained by averaging the ratio of the skin wrinkle density after use to the skin wrinkle density before use of the essence, and the measurement results are summarized in Table 9 below.
상기 표 9에서 알 수 있듯이, 에피프리델라놀을 포함한 제조예 2의 에센스를 사용한 경우, 에피프리델라놀을 포함하지 않은 비교예 2의 에센스를 사용한 경우보다 피부주름 개선 효과가 우수함을 알 수 있다. 또한 상기 시험 과정에서 제조예 2의 에센스에 의한 피부 자극이나 부작용은 발견되지 않았다.
As can be seen from Table 9, when the essence of Preparation Example 2 containing epifredolanol was used, it was found that the effect of improving skin wrinkles was superior to that of the essence of Comparative Example 2 which did not contain epifredelanol . No skin irritation or side effects due to the essence of Preparation Example 2 were found in the above test procedure.
상기의 결과들을 종합해보았을 때, 에피프리델라놀을 포함한 본원발명의 조성물이 콜라겐 합성 및 라미닌 5의 합성을 촉진하는 것을 확인할 수 있었으며, 이에 따라 실질적으로 피부주름 개선 및 피부탄력 증진 효과를 지님을 확인할 수 있었다.
When the above results are summarized, it was confirmed that the composition of the present invention including epipredelanol promotes collagen synthesis and synthesis of laminin 5, thereby substantially improving skin wrinkles and skin elasticity I could confirm.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시 예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.
<110> LG HOUSEHOLD & HEALTH CARE LTD. <120> Composition for improving skin wrinkle comprising epifriedelanol <130> PA121064KR <160> 4 <170> KopatentIn 2.0 <210> 1 <211> 56 <212> DNA <213> Artificial Sequence <220> <223> Laminin5beta3 primer F <400> 1 tacccatacg acgtaccaga ttacgctcaa acaaacttga gagtcaattt caccag 56 <210> 2 <211> 48 <212> DNA <213> Artificial Sequence <220> <223> Laminin5beta3 primer R <400> 2 cgggtggaat tcactggcct ccatggccaa ggtccggtct ggacactg 48 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GAPDH primer F <400> 3 ctgatgcccc catgttcgt 19 <210> 4 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GAPDH primer R <400> 4 tgtgaggagg ggagattca 19 <110> LG HOUSEHOLD & HEALTH CARE LTD. <120> Composition for improving skin wrinkling comprising epifriedelanol <130> PA121064KR <160> 4 <170> Kopatentin 2.0 <210> 1 <211> 56 <212> DNA <213> Artificial Sequence <220> <223> Laminin 5beta 3 primer F <400> 1 tacccatacg acgtaccaga ttacgctcaa acaaacttga gagtcaattt caccag 56 <210> 2 <211> 48 <212> DNA <213> Artificial Sequence <220> <223> Laminin 5beta 3 primer R <400> 2 cgggtggaat tcactggcct ccatggccaa ggtccggtct ggacactg 48 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GAPDH primer F <400> 3 ctgatgcccc catgttcgt 19 <210> 4 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> GAPDH primer R <400> 4 tgtgaggagg ggagattca 19
Claims (14)
A cosmetic composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient.
The cosmetic composition for improving skin wrinkles or skin elasticity according to claim 1, wherein the composition promotes the synthesis of collagen or laminin 5 or inhibits degradation.
The method according to claim 2, wherein the inhibition of collagen or laminin 5 degradation is accomplished through the synthesis of TIMP-1 (Tissue Inhibitors of Matrix Metalloproteinase-1) or the synthesis of PAI-1 (Plasminogen activator inhibitor-1) A cosmetic composition for improving skin wrinkles or improving skin elasticity.
The cosmetic composition according to claim 1, wherein the epipurdelanol content is 1 × 10 -6 to 10% by weight based on the total weight of the composition.
The cosmetic composition according to claim 1, wherein the cosmetic composition is at least one selected from the group consisting of a solution, an emulsion, a suspension, a paste, a lotion, a milk, a cream, a lotion, a surfactant-containing cleansing oil, a soap, a liquid cleansing agent, Wherein the cosmetic composition has a formulation selected from the group consisting of a gel, a pack, a soft water, a sunscreen, a makeup base, a foundation, a powder, a makeup removing agent and a detergent.
The composition according to claim 1, which further comprises at least one member selected from the group consisting of water, a surfactant, a moisturizer, a lower alcohol, a chelating agent, a bactericide, an antioxidant, an antiseptic, A cosmetic composition for enhancing elasticity.
A functional cosmetic composition for improving skin wrinkles or skin elasticity comprising the composition of any one of claims 1 to 6.
A pharmaceutical composition for preventing or treating skin wrinkles comprising epifriedelanol as an active ingredient.
The pharmaceutical composition according to claim 8, wherein the composition promotes the synthesis of collagen or the synthesis of laminin 5, or inhibits degradation.
The pharmaceutical composition according to claim 9, wherein the inhibition of collagen or laminin 5 degradation is achieved through the synthesis of TIMP-1 or the synthesis of PAI-1.
The pharmaceutical composition according to claim 8, wherein the pharmaceutical composition is selected from the group consisting of ointments, creams, tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aqueous solutions, A pharmaceutical composition for preventing or treating wrinkles of a skin having a selected formulation.
The pharmaceutical composition according to claim 8, wherein the composition further comprises a pharmaceutically acceptable excipient.
The pharmaceutical composition according to claim 12, wherein the pharmaceutically acceptable excipient is selected from the group consisting of a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent, a lubricant, a stabilizer, a perfume, water, a lower alcohol, a thickener, Preservatives, antibiotics, antioxidants, antifoaming agents, antimicrobial agents, antifungal agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, flocculants, humectants, fragrances, fragrance carriers, preservatives, , A sugar derivative, a sunscreen agent, a vitamin, a plant extract, and a wax.
A food composition for improving skin wrinkles or skin elasticity comprising epifriedelanol as an active ingredient.
Priority Applications (1)
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KR1020130001778A KR20140089848A (en) | 2013-01-07 | 2013-01-07 | Composition for improving skin wrinkle comprising epifriedelanol |
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KR1020130001778A KR20140089848A (en) | 2013-01-07 | 2013-01-07 | Composition for improving skin wrinkle comprising epifriedelanol |
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KR1020130001778A KR20140089848A (en) | 2013-01-07 | 2013-01-07 | Composition for improving skin wrinkle comprising epifriedelanol |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20170084845A (en) * | 2016-01-13 | 2017-07-21 | 한국과학기술연구원 | Anti-aging composition comprising aster plant extracts |
WO2019013365A1 (en) * | 2017-07-11 | 2019-01-17 | 한국과학기술연구원 | Anti-aging composition containing aster l. plant extract as active ingredient |
-
2013
- 2013-01-07 KR KR1020130001778A patent/KR20140089848A/en not_active Application Discontinuation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20170084845A (en) * | 2016-01-13 | 2017-07-21 | 한국과학기술연구원 | Anti-aging composition comprising aster plant extracts |
WO2019013365A1 (en) * | 2017-07-11 | 2019-01-17 | 한국과학기술연구원 | Anti-aging composition containing aster l. plant extract as active ingredient |
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