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.

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。

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.

慢性阻塞性肺病稳定期患者表皮功能改变及其临床意义

目的探讨肺部疾病患者与健康老人表皮生物物理特性是否存在差别。方法于2022年1月~3月收集50例慢性阻塞性肺病(COPD)老年患者和50例无肺病健康老年志愿者(61~91岁)。用GPSkin Barrier检测仪测量角质层含水量和经皮水分丢失率,用便携式酸碱度仪测量皮肤表面pH。结果(1)两组间面部、左臂和左腿的透皮水分丢失率无显著差异;(2)COPD患者左臂和左腿的角质层含水量显著降低(P<0.01),而面部角质层含水量无显著差异;(3)COPD患者左臂和左腿皮肤表面PH值显著高于无肺病者(P<0.01),但是面部皮肤表面pH无显著差异。结论COPD的老年患者皮肤衰老加速,表现为皮肤角质层含水量下降和皮肤pH值升高。对于COPD患者,修复表皮功能具有重要的临床意义。

表面活性剂与皮肤相互作用的研究进展

表面活性剂作为个人护理清洁产品的主要清洁成分,会直接接触皮肤进而与皮肤产生不同的作用。表面活性剂对皮肤的刺激性与其结构、类型、浓度、暴露时间、皮肤状态等多种因素相关。在清洁过程中,皮肤表面的污垢被表面活性剂增溶带入水中,表面活性剂也会与细胞间脂质相互作用加剧对皮肤屏障功能的破坏,导致皮肤干燥紧绷。但随着表面活性剂的进一步渗透并迁移到更深的皮层,会对活的表皮细胞如角质形成细胞产生破坏作用,并引起皮肤的局部炎症反应。文章简要概述了表面活性剂在水溶液中的基本性质及其结构与刺激性的联系,对表面活性剂的皮肤渗透理论模型、以及对皮肤脂质和活细胞的影响进行了归纳总结,并从个人护理产品配方角度出发,对表面活性剂降低皮肤刺激性的方法进行了可行性的展望。

当归饮子及其拆方对慢性湿疹豚鼠皮毛疏泄与润泽功能状态的影响

目的观察当归饮子“疏泄”与“润泽”药组对慢性湿疹豚鼠皮肤角质层含水量、经皮水分散失量的影响,研究当归饮子组方结构及其调控皮毛疏泄与润泽的作用机制。方法将40只雄性豚鼠随机分为正常组、模型组、当归饮子全方组、当归饮子去润泽药组、当归饮子去疏泄药组,每组8只。除正常组外,其余组豚鼠均采用2,4-二硝基氯苯丙酮液涂背诱导慢性湿疹样病变。造模成功后,正常组和模型组给予纯净水灌胃,当归饮子全方组给予当归饮子全方水煎液6.82 g/kg灌胃,当归饮子去润泽药组给予当归饮子去润泽药水煎液4.26 g/kg灌胃,当归饮子去疏泄药组给予当归饮子去疏泄药水煎液3.10 g/kg灌胃,均1次/d,连续灌胃2周。记录造模结束当日和末次灌胃结束当日各组豚鼠背部皮损评分,应用多功能皮肤测试仪测定皮肤角质层含水量和经皮水分散失量。结果造模结束当日,各造模组皮损评分、皮肤角质层含水量、经皮水分散失量比较差异均无统计学意义(P均>0.05);末次灌胃结束后,模型组皮损评分、经皮水分散失量均明显高于正常组(P均<0.05),皮肤角质层含水量明显低于正常组(P<0.05);与模型组比较,当归饮子全方组、当归饮子去疏泄药组、当归饮子去润泽药组皮损评分、经皮水分散失量均明显降低(P均<0.05),皮肤角质层含水量均明显升高(P均<0.05);当归饮子去疏泄药组和当归饮子去润泽药组皮肤角质层含水量均明显低于当归饮子全方组(P均<0.05)。结论当归饮子可提高皮肤角质层含水量,减少经皮水分散失量,其作用与当归饮子“疏泄”与“润泽”配伍组方用药密切相关。

经皮免疫治疗的临床和动物研究进展

变应原特异性免疫治疗(AIT),即脱敏治疗,被认为是唯一可能改变变态反应疾病自然进程的对因疗法。传统制剂如安脱达与阿罗格采用皮下注射途径,称为皮下注射免疫治疗(SCIT)。舌下含服免疫治疗(SLIT)自1998年起获批应用,是SCIT的有效替代。此外,为提高患者依从性并安全有效地诱导免疫耐受,通过皮肤、口服以及淋巴结内注射等新途径的免疫治疗正在积极开展临床研究。本文重点阐述经皮免疫治疗(EPIT)的作用机制,临床和动物研究的最新进展,以及未来的发展方向,为EPIT的应用与推广提供重要的理论参考。

一种含多肽的保湿原料的制备及其在化妆品中的应用

研究一款名为水光肽的保湿剂的制备及其在化妆品中的保湿功效,水光肽的主要活性成分为甜菜碱、海藻糖、吡咯烷酮羧酸钠(PCA钠)、棕榈酰五肽-4、聚(三肽-6)。人体试验表明,在使用含质量分数5%水光肽的样品组后1、3、6 h,与使用不含水光肽的安慰剂组相比,角质层水分含量明显升高;体外试验发现,水光肽对人永生化角质细胞(HaCaT)的水通道蛋白3(AQP3)表达具有极其显著的上调作用,具有良好的保湿效果。

果酸换肤术联合强脉冲光对中度寻常性痤疮患者皮肤屏障功能及TEWL的影响

目的探讨果酸换肤术联合强脉冲光在中度寻常性痤疮(acne vulgaris,AC)患者中的疗效。方法方便选取2020年3月—2022年6月阳光融和医院收治的96例中度AC患者,按随机数表法分为对照组(n=48)采用果酸换肤术治疗,观察组(n=48)在对照组基础上加用强脉冲光治疗。两组患者均于治疗后持续随访12周。对比两组患者皮肤屏障功能、经表皮失水率(trans epidermal water loss,TEWL)水平、临床疗效及并发症。结果观察组治疗后角质层含水量高于对照组,皮脂水平低于对照组,差异有统计学意义(P<0.05);观察组治疗后TEWL水平低于对照组,差异有统计学意义(P<0.05);观察组临床总有效率(95.83%)高于对照组(83.33%),差异有统计学意义(χ^(2)=4.019,P<0.05);观察组并发症发生率(4.17%)低于对照组(16.67%),差异有统计学意义(P<0.05)。结论果酸换肤术联合强脉冲光能够改善中度AC患者皮肤屏障功能,降低TEWL水平,疗效显著,还可减少并发症的发生。

2种测量角质层水分含量仪器的相关研究

比较Corneometer和MoistureMeterSC 2种仪器对角质层水分含量测量结果的一致性,为人体临床应用提供理论依据。在24名志愿者手臂内侧分别使用Corneometer和MoistureMeterSC进行角质层水分含量测量,通过Pearson相关系数对2种检测角质层水分含量的仪器进行相关性分析。通过Bland-Altman进行一致性分析,应用统计学方法对2种方法测量的结果进行差异性分析,同时用CV值评估设备的重复性。结果显示,2种仪器在涂抹区域及未涂抹区域测量角质层水分含量时具有良好的相关性,r在0.667~0.902,CV在6%以下,仪器重复性都较好;在未涂抹区域一致性较差,两者之间的差值距离0值较远,并且有显著性,在涂抹产品后一致性较好,Corneometer和MoistureMeterSC有较弱的一致性。Corneometer和MoistureMeterSC重复性都较好,并且具有良好的相关性,但是一致性较差,不能替代,使用时根据临床实际需求进行选择。

植物油在沐浴油中的应用

研究用添加大豆油、葡萄籽油、向日葵籽油、甜杏仁油、橄榄油、菜籽油分别制备了6款沐浴油,考察了贮藏稳定性,测试了6款沐浴油使用后的角质层含水量和经皮水分流失率变化,采用玉米醇溶蛋白法测试了刺激性。结果表明,添加6种植物油的沐浴油稳定性考察无异常情况,均有一定的保湿和降低表面活性剂体系刺激性的效果,保湿效果:向日葵籽油>葡萄籽油>橄榄油>大豆油>甜杏仁油>菜籽油。