First stereoselective total synthesis of triumfettamide

The first total synthesis of triumfettamide (1) is described. The asymmetric syntheses of two highly functionalized units—α-hydroxylated C17 monounsaturated fatty acid unit (2) and C26 phytosphingosine (3) have been accomplished involving Sharpless asymmetric dihydroxylation, Sharpless kinetic resolution, regioselective epoxide opening, regioselective DIBAL-H reduction of acetal, Wittig olefination as the key steps. Finally N-acylation of phytosphingosine 3 with (2R,6Z)-2-hydroxy-6-heptadecenoic acid 2 followed by DDQ deprotection of PMB, provided target compound 1.     

Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.     

反倾层状边坡弯曲折断的应力及挠度判据

以地质分析为基础 ,将反倾层状边坡的任意岩层概化为受复合作用力的板梁模型 ,通过简单的力学解析 ,开展了反倾层状岩石边坡弯曲折断判据的研究。依据岩层折断时和相临岩层的瞬时关系 ,将岩层下部视为瞬时临空状态 ,考虑岩层自重荷载和上部岩层附加荷载 (上部岩层重力荷载、层间摩擦力 )的共同作用 ,基于最大拉应力准则 ,提出了岩层弯曲折断的应力判据 ;依据应力判据 ,得到了岩层弯曲折断的挠度判据 ;利用应力判据及挠度判据 ,可实现反倾层状边坡弯曲折断的现场判定及其控制设计     

Triphasic FE Modeling of the Skin Water Barrier

A skin–air model is developed to model the water barrier function of skin. The skin model is a porous solid saturated with a monovalent salt solution. The air model is a vapor diffusion model in non-moving air. In vivo measurements of water loss from human skin under varying ambient conditions are used to validate the model.     

Influence of oleic acid on the structure of a mixture of hydrated model stratum corneum fatty acids and their soaps

The phase behaviour of a hydrated (32% (w/w) water) mixture of saturated and unsaturated fatty acids and their soaps has been examined. By progressively increasing the proportion of oleic acid, it could be shown that this unsaturated component exists partly as a separate phase within the others. The unsaturated fatty acids form an H_II phase at 25°C, whereas the saturated fatty acids form a fatty acid—soap crystal under the conditions employed. The results help to explain the role played by the fatty acids (and also cholesterol) within the lipid fraction of human stratum corneum. A feature of this study is a comparison of the results obtained by X-ray diffraction, differential scanning calorimetry and Fourier transform infrared spectroscopy.     

Possibilities for human skin characterization based on strongly reduced Raman spectroscopic information

Loss‐of‐function mutations in the gene coding for filaggrin are the single most important risk factor for development of atopic dermatitis and associated allergic rhinitis and asthma. Filaggrin is enzymatically degraded to natural moisturizing factor (NMF) in the stratum corneum (SC). In vivo Raman spectra of human skin can be used to quantify the NMF concentration in SC and thereby identify carriers of a loss‐of‐function mutation in the gene coding for filaggrin, which results in decreased NMF content. Here, we demonstrate that strongly reduced Raman spectral information is sufficient to make this differentiation. This is an important step towards development of a dedicated diagnostic device of reduced complexity, size and cost as compared to current state‐of‐the‐art Raman equipment. A genetic algorithm was used to select the spectral regions needed to classify skin based on normal or reduced NMF content in SC. Using the NMF content based on full spectral information as gold standard, only four Raman regions were required to create a linear discriminant analysis model that can differentiate between skin with low NMF and skin with normal NMF with a prediction accuracy of 93 %. Copyright © 2013 John Wiley & Sons, Ltd.     

Investigation of the cosmetic ingredient distribution in the stratum corneum using NanoSIMS imaging

In order to understand the mechanisms of action of cosmetic ingredients, it is important to establish the distribution of the component agents within the epidermis of the skin. To date, time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been used to detect cosmetic ingredients in the skin. However, it is technically difficult to investigate the distribution of the agents in the stratum corneum using TOF-SIMS. Therefore, an analytical method with higher spatial resolution is required. In this study, we investigated an imaging analysis technique based on NanoSIMS to detect cosmetic ingredients in the skin. Pig skin was used as a model for human skin. The sample was treated with a cosmetic formulation containing ¹⁵N-labelled pseudo-ceramide (SLE). The sample was frozen with liquid nitrogen and cross-sections were cut using a cryomicrotome. As a result, the fine layer structure of the corneocytes was clearly observed by using NanoSIMS. Our studies indicate that SLE penetrates into the stratum corneum via an intercellular route. We conclude that application of NanoSIMS analysis can contribute to a better understanding of the function of cosmetic ingredients in the skin.     

Corrosion of Nickel-based Alloy G30 in the Stratum Water Containing H2S/CO2

The influences of temperature and CO2 pressure on the corrosion of nickel-based alloy G30 in the stratum water containing H2S/CO2 were investigated with the aid Mott-Schottky analysis and scanning electron microscopy（SEM） of electrochemical impedance spectroscopy（EIS）, The results indicate that alloy G30 is in the passive state in the stratum water, which is related to the formation of the passive film on its surface. This passive film can significantly protect the substrate from further corrosion. And the film protection is enhanced with decreasing temperature and CO2 pressure. Auger electron spectrometry（AES） and X-ray photoelectron spectrometry（XPS） results reveal that the passive film shows the double-layer structure, i.e. the inner chromium oxide and the outer iron/nickel spinel oxides or hydroxides with Mo oxides dispersing throughout the inner and outer scale.     

In vivo transdermal delivery using a shock tube

A shock tube was utilized for transdermal delivery in fuzzy rats. Rhodamine-B dextran, 10 kDa molecular weight, was used as the probe molecule. Shock waves were generated by a two-stage shock tube. A single shock wave was applied onto the skin to permeabilize the stratum corneum. Subsequently, the dextran solution diffused through the stratum corneum into the epidermis. Fluorescence microscopy of biopsies showed that the dextran was delivered to a depth of m into the skin. Thus, the shock tube could become an inexpensive device for transdermal drug delivery. Received 19 February 2000 / Accepted 29 June 2000     

低聚壳聚糖与角质层蛋白相互作用的体外研究

以脱脂鼠角质层和提取角蛋白为模型,利用电化学交流阻抗谱、SEM、DSC、FTIR等手段,研究了低聚壳聚糖及氨基葡萄糖与角质层蛋白之间的相互作用.结果发现,氨基葡萄糖溶液处理不影响脱脂角质层膜的阻抗,而低聚壳聚糖溶液处理却可明显降低脱脂角质层膜的阻抗,阻抗值由3.79×106Ω·cm2降至8.379×105Ω·cm2.此外,壳聚糖溶液和氨基葡萄糖溶液都可明显破坏角蛋白表面致密均匀的结构,并使得角蛋白二级结构中α-螺旋结构含量减少,同时推动角蛋白α-螺旋结构向β-折叠结构和无规则卷曲结构转变.这些结果表明低聚壳聚糖与角质层蛋白相互作用,一方面可有效降低鼠角质层结构的紧密程度,另一方面可影响角蛋白的微结构,使其结构松散并出现微细孔道,从而为药物的经皮吸收与传送疏通了通道.