보건의료기술진흥사업;주름개선 및 피부노화 방지용 칼슘신호전달 조절 기능성 화장품 소재의 개발
Health & Medical Technology R&D Program;Development of cosmeceutical ingredients related with calcium signal for anti-skin aging and the anti-wrinkling
각질형성세포와 섬유아세포에서 칼슘신호전달 조절 기능을 지닌 물질을 합성, 개발하고 이를 이용하여 피부 노화 개선 효능을 지닌 기능성 화장품 원료인 L12를 개발하였다. 특히 본 연구 과제를 통하여 개발된 L12는 섬유 아세포의 칼슘신...
각질형성세포와 섬유아세포에서 칼슘신호전달 조절 기능을 지닌 물질을 합성, 개발하고 이를 이용하여 피부 노화 개선 효능을 지닌 기능성 화장품 원료인 L12를 개발하였다. 특히 본 연구 과제를 통하여 개발된 L12는 섬유 아세포의 칼슘신호 전달 기전을 활성화하며, 세포 증식 촉진, 콜라겐 합성 촉진 등의 효능을 지닌 것으로 밝혀졌으며, 내인성 노화와 광노화 동물 모델에서 유의한 주름 개선 효능을 지닌 것으로 나타났다. 이와 함께, 레티놀에 비하여 피부 자극이 매우 낮은 것으로 나타났다.
Abstract ▼
A lot of molecules are currently used or under being investigated as anti-aging agents and diverse underlying mechanisms are sugge...
A lot of molecules are currently used or under being investigated as anti-aging agents and diverse underlying mechanisms are suggested for each of these molecules. A lot of molecules, however, are not appropriate for practical application, because of their insufficient in vivo efficacy or side-effects, such as skin irritation. Previously, it was suggested that sphingosine kinase activator may be used for anti-aging, mainly through the sphingosine-1-phosphate involved signaling. A newly synthesized molecules, K6PC-5, is a new anti-aging cosmeceutical agent, and its application in either intrinsically aged or UV-induced aged mice have been reported. As a continuation of the previous researches, K6PC-5 derivative molecules using amino acids were synthesized in this research and their anti-aging and wrinkle improving efficacy was tested in vitro and in vivo. Firstly, newly synthesized molecules are tested for their activity on calcium signaling, proliferation of cultured human fibroblast and collagen synthesis in fibroblast. In addition, effect on the terminal differentiation of human keratinocytes was also evaluated. Among the tested molecules, K6-L12 showed most significant calcium signaling in both the cultured keratinocyte and fibroblast, and also induced proliferation of fibroblast and increased collagen synthesis. In order to verify the anti-aging efficacy of K6-L12 on intrinsically aged skin, murine aged mice model was established and dermal changes were investigated. When 1% K6-L12 was topically applied twice a day for 2 wks in 56-wks aged mice skin, and functional measurements and histologic observation was performed. No changes in transepidermal water loss and skin capacitance was observed between vehicle treated and K6-L12 treated groups. However, dermal thickness was significantly increased in K6-L12 treated skin and, the increased number of fibroblast and collagen density was also observed. In a photo-aged model induced by chronic UV-irradiation, topical application of L12 also improved collagen density of dermal tissue and also skin barrier function. When topical retinol was used as a positive control, significant skin irritation was observed in retinol treated skin site, but L12 treated site did not show irritation, which suggests that L12 can be used as an anti-aging agent for sensitive skin. In order to access the potential toxicity of L12, 6 kinds of toxicity tests were performed in non-clinical CRO organization. As results, L12 did not result in any significant toxicity under tested condition, and it can be concluded that L12 is a safe cosmetic ingredient. It was also listed in the International Cosmetic Ingredient Dictionary (ICID). In order to use L12 as a cosmetic ingredient, large scale synthesis was performed and its final yield was 80%, and its cost was evaluated as HRW 101,200/kg. Currently, balm type product is under clinical investigation for verifying its anti-wrinkle efficacy. In order to develop new molecules which having skin barrier improving activity, we have screened the synthesized molecules for their effects on skin barrier function, and identified several molecules are beneficial effects on barrier function. Interestingly, the potential mediating molecules were suggested as an anti-microbial peptides (AMPs) and, using the synthesized molecules, their effects on mRNA expression of AMPs was evaluated using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). As a result, L19 was identified as having stimulating effects on the AMPs mRNA expression in cultured human keratinocytes, without affecting the proinflammatory cytokines production. In a chronic dermatitis model induced by long-term oxazolone application, considerable increase of epidermal AMPs was observed in 1% L19 applied skin. These results suggest that K6-L19 may be used as a possible medication for infectious skin diseases and atopic eczematous lesions.
