FINITE ELEMENT METHOD ON NUMERICAL SIMULATION OF STRATUM CORNEUM'S PENETRATION PROPERTY

How the outer substance could penetrate through the skin lies in the stratum corneum, because it is the main barrier in the multi-layers of the skin. Supposing the keratin cell with a special geometry as tetrakaidecahedron, the penetration property of stratum corneum was the key problem which was numerically simulated with finite element method. At first the discretization of the stratum corneum region was given in two steps： first, the discretization of the keratin cell; second, the discretization of fattiness that surrounds the keratin. Then there was the work of numerical simulation. In this procedure, the finite element method and the multi-grid method were used. The former was to obtain the discretization of basic elements; the latter was to decrease the high frequency error. At last the visualization of the numerical simulation was shown.

TEM Assessments of the Restructuring Effects of an Emollient Cream on the <i>stratum corneum</i>

The structure of the stratum corneum contributes to the barrier function of the epidermis. Skin barrier recovery is of utmost importance after epidermal tissue damage. The aim of this study was to describe, at the cellular level, the structural effects resulting from topical application of a hand-cream onto normal skin and to investigate the potential repair mechanisms induced by the emollient on altered tissue. Transmission electron microscopy (TEM) was used to compare the architectures of the horny layers from: 1) ex-vivo cultured human skin;2) skin treated by topical application of a hand-cream emulsion;3) explants exposed to sodium lauryl sulfate (SLS);4) SLS-treated explants that underwent subsequent topical application of the emollient emulsion. These TEM assessments allowed identifying the structural changes occurring in the stratum corneum of skin explants exposed to SLS and/or treated with an emollient. Results strongly suggest that both, SLS-induced damage and emollient-driven repair process take place in the stratum corneum, at the cellular level. One can envisage that the observed restructuring effects after topical application of the skin-care product are likely to ameliorate or restore the barrier function of the stratum corneum. In this, the properties of the emollient go beyond the cosmetic feel.

A Consensus Modeling Approach for the Determination of Stratum Corneum Thickness Using In-Vivo Confocal Raman Spectroscopy

The measurement of stratum corneum (SC) thickness from in-vivo Raman water concentration depth profiles is gaining in popularity and appeal due to the availability and ease of use of in-vivo confocal Raman measurement systems. The foundation of these measurements relies on high-quality confocal Raman spectroscopy of skin and the robust numerical analysis of water profiles, which allow for accurate determination of SC thickness. These measurements are useful for studying intrinsic skin hydration profiles at different body sites and for determining hydration properties of skin related to topically applied materials. While the use of high-quality in-vivo Raman instrumentation has become routine and its use for SC thickness measurement widely reported, there is lack of agreement as to the best method of computing SC thickness values from Raman water profiles. Several methods have been proposed and are currently in use for such computations, but none of these methods has been critically evaluated. The work reported in this paper describes a new method for the determination of stratum corneum thickness from in-vivo confocal Raman water profiles. The method represents a consensus approach to the problem, which was found necessary to apply in order to properly model and quantify the large diversity of water profile types encountered in typical in-vivo Raman water measurement. The methodology is evaluated for performance using three criteria: 1) frequency of minimum fitting error on modeling to a standard numerical function;2) frequency of minimum model error for consensus vs. individual SC thickness values;and 3) correlation with reflectance confocal microscopy (RCM) values for SC thickness. The correlation study shows this approach to be a reasonable replacement for the more tedious and time-consuming RCM method with R2 = 0.68 and RMS error = 3.7 microns over the three body sites tested (cheek, forearm and leg).

Influence of short chain ceramides and lipophilic penetration enhancers on the nano-structure of stratum corneum model membranes studied using neutron diffraction

Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides （CER）[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid （OA） and isopropyl myristate （IPM） on the lipid nanostrueture. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. 2H NMR spectroscopy was used to study the impact of the ceramides＇ degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The 2H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix. The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum comeum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases （assigned as phase A and B） appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented.

Different Modes of the Effect of 1,2-Propanediol and Azone on Stratum Corneum Lipids

The stratum corneum (SC) controls the diffusion and penetration of drugs into and through the skin. In this investigation, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were used to study the effect of two enhancers, 1,2 propanediol and azone, on lipids extracted from SC (SC lipids). The two enhancers affected the SC lipids. However, their function modes were different. The penetration enhancing mechanisms of the two enhancers are discussed based on their effects on SC lipids and on their efficiencies in arbutin permeation enhancement.

Numerical Simulation of Skin Formation: The Relationship between Transepidermal Water Loss and Corneum Thickness

Skin moisturizing has drawn attention in terms of beauty and anti-aging industries. However, it is difficult to observe the inside of the epidermis and the relationship between the epidermis and water content is not yet clear. Computational simulations can be useful in understanding such mechanisms of skin formation. A particle model was used to simulate three-dimensional skin turnover, and the results reproduced the epidermal skin turnover phenomenon. In this study, a diffusion model is introduced into this simulation model and a moisture diffusion analysis of the epidermis was performed. In particular, transepidermal water loss (TEWL) was modeled by considering diffusion and surface evaporation in the stratum corneum and other layers. The relationship between the moisture content and the keratin detachment was considered, and the exfoliation condition of keratin based on the moisture content was calculated in the model. As a result, it was possible to calculate the intraepidermal water content distribution in the skin using the particle model. It was also possible to reproduce phenomena such as keratin thickening due to increase of TEWL. This phenomenon is consistent with cases of dry skin. In the future, it will be necessary to introduce a change in TEWL according to the thickness of the stratum corneum and the diffusion coefficient.

Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

Supporting Skin Structure and Its Barrier Functions with Evidence-Based Skin Care Ingredients

The epidermis, and in particular its outermost layer, the stratum corneum, contributes much of the barrier function of the skin and is a readily visible representation of skin health. Maintaining the health of the skin barrier has arguably become more important than ever in the modern world, in which a large majority of people are exposed to environmental insults. These external factors can damage the integrity of the skin barrier and prematurely age the skin. Therefore, it has become increasingly important to maintain and protect the stratum corneum. Here, we briefly review the complex, multilayered structure of the skin and relate it to clinically translatable function, with an emphasis on the stratum corneum. In the context of epidermal structure and function, the formulation and clinical data for Phelityl® Reviving Cream will be reviewed. Phelityl Reviving Cream was shown to be associated with improvements in both immediate- and long-term parameters, including a significant positive effect on the skin barrier and immediate and long-lasting hydration.

脂质链长度与特应性皮炎相关性研究进展

特应性皮炎(atopic dermatitis,AD)是一种慢性、复发性炎症性皮肤病。越来越多证据表明,皮肤屏障功能障碍是导致AD的重要原因。皮肤最外层的脂质基质角质层(stratum corneum,SC)对皮肤屏障功能的维系至关重要。大量研究显示,角质层脂质含量降低、链长度缩短、神经酰胺(ceramide,CER)亚类水平改变以及炎症反应等都会影响AD患者皮肤屏障功能。本文就角质层脂质链长度与AD患者皮肤屏障功能的关系做一综述。

美满霉素与异维A酸对痤疮患者血清TNF-α、hs-CRP、IL-6水平、角质层含水量的影响分析

目的:探讨美满霉素与异维A酸对痤疮患者血清炎性因子及角质层含水量(MCOC)的影响。方法:选取2019年9月—2021年6月尉氏县人民医院收治的127例面部痤疮患者作为研究对象,根据治疗方案不同将患者分为对照组(n=63)与研究组(n=64)。对照组患者采用异维A酸治疗,研究组患者采用美满霉素联合异维A酸治疗,两组患者均治疗6周。对比两组患者治疗前后MCOC、肿瘤坏死因子α(TNF-α)、经表皮失水量(TEWL)、白细胞介素6(IL-6)、角质层样本蛋白质含量、C-反应蛋白(hs-CRP)水平及不良反应。结果:治疗后,研究组患者的TEWL、角质层样本蛋白质水平低于对照组,MCOC水平高于对照组,差异有统计学意义(t=3.703、2.769、3.504,P<0.05);治疗后,研究组患者的TNF-α、hs-CRP、IL-6水平均低于对照组,差异有统计学意义(t=4.280、19.008、3.512,P<0.05);两组患者不良反应比较,差异无统计学意义(χ^(2)=0.401,P>0.05)。结论:美满霉素联合异维A酸治疗能够有效提高痤疮患者角质层含水量,降低血清TNF-α、hs-CRP、IL-6水平并改善患者皮损症状。

山茶花及灵芝精萃物保湿霜对人体皮肤微生态的影响

为探讨天然植物源提取物护肤品对人体皮肤微生态的影响,以山茶花及灵芝精萃物保湿霜为供试物,采用16S rRNA及ITS rRNA基因高通量测序方法,结合电容法测定皮肤角质层含水量,揭示了保湿霜使用前及使用后14 d和28 d时皮肤微生物群落多样性及种群结构的变化过程与内在原因。研究发现,山茶花及灵芝精萃物保湿霜的使用增加了皮肤细菌群落的多样性,但同时也降低了真菌种群的物种数量。D0、D14及D28组样本分别聚类在不同区域且具备明显区分度。两种保湿霜的使用未改变皮肤微生物在门水平上的群落构成,使用前后细菌及真菌优势门相同。在属水平上,山茶花及灵芝精萃物保湿霜的使用显著增加了细菌中葡萄球菌属和表皮杆状菌属的相对丰度,但真菌群落的相对丰度呈无序变化。此外,两种保湿霜的使用均大幅提升了皮肤角质层的水分含量。结果表明,山茶花及灵芝精萃物保湿霜具有补水保湿功效,可有效调节并改善皮肤菌群的微生态平衡。

一种油凝胶型手部磨砂膏的制备及功效评估

本研究制备了一种油凝胶型的手部磨砂膏,以聚氨基甲酸酯和蜡酯为增稠剂、悬浮剂,让磨砂粒子稳定悬浮在油凝胶体系中,从流变测试结果可知,该油凝胶具有黏弹性,为假塑性流体,具有剪切变稀的特性。体外鸡胚绒毛尿囊膜(CAM)刺激性测试中显示为轻刺激。在人体功效测试中,使用该手部磨砂膏15 min后测试手背皮肤角质层水分含量显著提升(P<0.05),经表皮水分流失率(TEWL)降低4.79%,皮肤粗糙度参数SEr值显著增加23.94%(P<0.05),说明该样品具有滋润、不损伤皮肤屏障、改善皮肤粗糙的功效。

我国正常人皮肤表面皮脂和水分含量的研究

目的:了解我国不同年龄、不同性别正常人皮肤角质层含水量、皮肤表面皮脂含量及皮肤皮脂的分泌速度。方法:利用皮肤表面皮脂测量仪和皮肤水分含量测量仪对我国北方325名正常人的前额及前臂屈侧皮肤皮脂量和皮肤含水量进行测量。结果:12岁以前,男女前额皮脂量无差异;13岁以后,男性前额的皮脂量明显高于女性。除36～50岁年龄组外,女性前额的皮脂分泌快于男性。男女前臂的皮脂量无差异。除男性13～35岁组的前额皮肤含水量高于女性外,其他各年龄组各部位男、女皮肤含水量无显著差别。13～35岁组男、女性前额的含水量均高于前臂。其他各年龄组前额和前臂皮肤含水量无明显部位差异。13～35岁组男性前额皮肤含水量最高。结论:正常人皮肤表面含水量和皮脂含量因性别、年龄和部位的不同而有差异。

氨甲环酸对玫瑰痤疮患者皮肤屏障功能和炎症反应的影响

目的:研究氨甲环酸对玫瑰痤疮患者皮肤屏障功能及炎症反应的影响。方法:对30例玫瑰痤疮患者采用自身左右脸对照的方法,治疗侧外用3%氨甲环酸溶液,对照侧外用基质溶液,每天2次。2周后评价双侧红斑程度、炎症性皮损数量及屏障相关生理指标[角质层含水量、经皮水分丢失(TEWL)、pH值1,并检测角质层完整性、角质层丝氨酸蛋白酶活性以及LL-37表达。结果:治疗侧较对照侧红斑程度轻,炎症性皮损数量显著减少(P<0.05);皮肤屏障相关生理指标、角质层完整性及乳酸刺激试验结果有显著改善,差异有统汁学意义(P<0.05);氨甲环酸还可以明显抑制角质层丝氨酸蛋白酶活性(P<0.05)和LL-37的表达。结论:外用氨甲环酸可通过抑制角质层丝氨酸蛋白酶活性及抗菌肽LL-37表达改善玫瑰痤疮患者受损的屏障功能,同时抑制炎症反应.可作为玫瑰痤疮治疗的辅助用药。

油酸经皮促透作用微观机理的研究

皮肤角质层是药物透皮吸收的主要屏障 ,而角质层类脂在角质层的屏障功能中起着主要的作用。本文的主要目的是研究透皮促进剂油酸导致角质层类脂形态上的变化及其降低表皮屏障功能的机理。 10 %的油酸 丙二醇应用于雄性Wistar大鼠的表皮 2h ,标本用四氧化钌固定后 ,电镜观察表明由于油酸的作用导致角质层类脂膜结构发生了显著的变化 ,破坏了其类脂膜的有序结构并在角化细胞间隙中形成大量腔隙。表明透皮促进剂油酸的主要作用机理是破坏角质层类脂膜结构及在角质层细胞间形成腔隙 。

护肤产品的保湿功能评价

介绍了一种测试化妆品护肤产品保湿效果的方法 ,检测了四十种不同配方保湿霜的相对保湿率 ,相对保湿率用来定义产品降低皮肤干燥度的有效性。用SKICON2 0 0型角质层水含量测试仪对使用产品前后的角质层水含量进行了测试 ,两种方法的相关性较好。

促透剂薄荷醇对大鼠皮肤角质层超微结构的影响

目的探讨薄荷醇经皮吸收促透作用的机制。方法运用光镜、扫描电镜和透射电镜观测薄荷醇对大鼠皮肤角质层结构的变化。结果薄荷醇组的表皮皱折明显增多,表皮间裂隙增宽,层与层间的间隙变得更大;角质层结构疏松,有孔穴样结构,排列紊乱,与表皮分离呈层状,脂质正常的板层状膜状结构大部分或全部消失,出现明显增厚的紊乱排列的中等致密凝絮块状结构。结论薄荷醇影响了角质层的有序排列,使角质层间的空隙变大,结构疏松,皮肤通透性增加。

D-柠檬烯和L-柠檬烯对盐酸川芎嗪透皮吸收的影响

目的研究手性对映体D-柠檬烯和L-柠檬烯对盐酸川芎嗪透皮吸收的影响及其作用机制。方法采用Franz扩-散池测定盐酸川芎嗪通过离体猪皮的透过量;红外光谱法测定角质层脂质中C-H对称和不对称伸缩振动吸收峰峰位及其峰面积;采用扫描电镜观察皮肤表面形态学变化,并新引入量化的概念———表观密度衡量角质鳞片脱落的程度。结果D-柠檬烯和L-柠檬烯对盐酸川芎嗪的促透量均高于对照组和氮酮组,这两种对映体促透剂产生的促透量无统计学差异(P>0.05),L-柠檬烯的时滞是D-柠檬烯的2.55倍。红外光谱结果显示:角质层脂质中的C-H伸缩振动吸收峰位移和峰面积的变化取决于所用的促透剂;两种对映体促透剂均引起对称振动和不对称振动吸收峰位移增大和峰面积减少。扫描电镜结果表明,不同的促透剂抽提角质层中的脂质,引起角质鳞片不同程度的脱落。结论D-柠檬烯和L-柠檬烯的促透量均高于对照组和氮酮组,并且以D-柠檬烯的时滞最短。两种对映体促透剂对盐酸川芎嗪的促透机制是多种原因共同作用的结果。

化学促进剂与鼠角质层脂质相互作用的ATR-FTIR

The mechanism of enhancers （methanol,chloroform,azone and thiozone） was studied in vitro in mouse stratum corneum （SC）.Attenuated total reflectance Fourier-transform infrared spectroscopy （ATR-FTIR） was applied to monitor the wavenumber shifts of CH2 stretching absorbance as well as the lipid content in the SC,which were used as criteria to explain the effect of the enhancers on mouse SC.The FTIR spectra record that treatment with these four enhancers would result in significant shifts toward higher wavenumber at vasCH2 and vsCH2 and the integration areas of vasCH2 and vsCH2 decrease when treatment of methanol and choloroform.It is concluded that these four enhancers could increase the gauche conformational isomer content of lipid CH2,made the lipid in the SC a more fluid state,thus the resistance of drug transdermal delivery was reduced.

蛇床子素在人皮肤角质层和去角质层皮肤中的分布测定

目的:研究抗银屑病蛇床子素贴剂经皮渗透后蛇床子素在人皮肤角质层和去角质层皮肤中的分布。方法:采用了胶带剥离、皮肤萃取法分别获取了人皮肤角质层、去角质层皮肤样本,用HPLC法测定了样本中的蛇床子素含量。结果:蛇床子素在人皮肤角质层的滞留量远大于去角质层皮肤的量。结论:蛇床子素在人皮肤内的滞留量与贴剂使用的时间呈线性,药物可以缓慢地扩散到皮肤的更深层而产生缓释效果。