이데베논을 함유한 비수계 피부유사 액정의 제조와 분석 및 항노화 화장품으로서의 응용

Abstract

Topical application of active substances has been widely investigated in recent years but their instability in water as well as the poor permeability of most active substances through the skin limits the use of topical drug delivery. This is the reason why transdermal administration is limited by the stratum corneum (SC), the outer layer of skin, considered as the main barrier to percutaneous absorption of drugs. The crystalline lamellar lipid layer in the intercellular region of SC obstructs the diffusion of active substances, reduces the efficiency of drug delivery into skin, and decreases the desirable effects such as whitening, anti-wrinkle, or moisturizing etc. Also, most of substances having anti-aging effects such retinoids, ubiquinones, and vitamin C derivatives become very unstable when they contact to water molecules which is the dominant ingredient of cosmetic formulations. Therefore, in order to encapsulate these substances stably and improve their transdermal delivery efficacy, it is necessary to develop the new encapsulation method having a similar structure to the SC, as well as protecting from the oxidation of these active substances. In this study, we designed the new model matrices having a densed lamellar structure similar to the structure and composition of SC, while we developed the preparation method of these model matices in non-hydrous condition. Also, we characterized the structural and thermal transitional behaviors with XRDs, DSC, and microscopes. In the application of cosmetic formulation, we studied the stabilities of idebenone-loaded model matrices, the recovery rate(%) of idebenone and the transdermal penetration of idebenone. For the efficacies of idebenone as an anti-aging challenger, we evaluated the collagen biosynthesis, collagenase inhibition, and elastase inhibition at in-vitro. Finally, we studied the practical anti-wrinkle efficacy of the gel cream containing idebenone encapsulated in the model matrix at in-vivo. PG molecules work as a solvent which can modulate the lipophilic portion of DSPC as well as the hydrophilic portion, differently from water molecules because it has a short hydrocarbon chain. Therefore, increasing the amount of PG in the mixture of DSPC and PG, it showed the phase transition to be gradually changed from anisotropic structures to other structures more close to isotropic ones and their appearances to be changed from solid-like states to liquid-like ones with more fluidity. Increasing PG made the lamellar repeat distance of DSPC more expanded than pure DSPC and the enthalpy change and the transition temperature more lowered than pure DSPC. These results explained that all of PG molecules contributed to swelling the DSPC-based lamellar phase and were also in good agreement with PM study. As soon as CER3 was incorporated into the lamellar phase, the characteristic LPP was appeared as well as the characteristic SPP, and the formation of separated CER3 crystalline phase was observed depending upon the increase of CER3 content with XRDs. Also, with DSC, it was shown that the increase of CER3 made the monotectic thermal transition be changed to the eutectic thermal transition which indicates the formation of separated CER3 crystalline phases and the main transition temperatures (Tc1) to be gradually decreased and the enthalpy change (△H) to be increased. Incorporating CHOL, the formation of LPP and SPP showed almost similar behaviors to CER3, but even incorporating small amounts of CHOL showed the characteristic peaks of CHOL which meant the existence of crystalline CHOL phase due to the immiscibility of CHOL with DSPC swollen by PG differently from CER3, and increasing CHOL made the intensity of the 1st order diffraction for LPP weakened as well as the intensities of the characteristic diffractions for DSPC. Also, in the results of DSC, it showed more complex thermal behaviors having several Tc than CER3 due to its bulky chemical structure. Incorporating both of CER3 and CHOL, it was founded that there was a specific ratio between CER3 and CHOL to form a homogeneous lamellar phase and the ratio appeared 1.5 : 1.5 for CER3 : CHOL. At in-vitro test, we studied the efficacy of idebenone about collagen synthesis, collagenese inhibition, and elastase inhibition. Idebenone significantly increased the collagen synthesis dependently upon idebenone concentration. And idebenone showed not to be significantly effective in the inhibition of collagenase and elastase activities. Therefore, idebenone was judged to be potent in the application of anti-aging cosmetics because of its ability to increase the collagen biosynthesis. At in-vivo, we proceeded human-applying experimentations for 24 women having skin wrinkles around their eye zone, cooperating with Ellead skin research center. For 12 weeks, we have tested anti-wrinkle efficacies comparing test cream to placebo cream by means of dermatologists… naked eye evaluation, replica-image analysis with skin visometer, and photographic monitoring with a high resolution digital camera. Test cream containing idebenone encapsulated into the skin analogue model matrix was confirmed to show the anti-wrinkle effect by dermatologists… naked eye evaluation and replica-image analysis, and the anti-wrinkle effect was also confirmed to be significant in statistics. Therefore, cosmetics containing idebenone encapsulated into this model matrix will be very potential in the application of anti-wrinkle cosmetics.