Integrated risk assessment of a hydroxyapatite-protein-composite for use in oral care products: a weight-of-evidence case study

Risk assessment of cosmetic ingredients represents a regulatory standard requirement in Europe and other regions. An integrated approach was designed to assess the safety of HPC, a particulate composite of hydroxyapatite and protein (gelatin) for use in oral care products, employing a weight-of-evidence assessment and considering specific physico-chemical properties and exposure conditions. An initial evaluation of the constituents suggested that their chemical nature does not represent a particular health hazard per se. Hydroxyapatite is the main component of teeth and bones in mammals; gelatin is used in food and assumed to be safe once a BSE/TSE risk has been excluded. In vitro screening tests were chosen to further evaluate the biocompatibility: Hen's egg test-chorioallantoic membrane (HET-CAM) to assess irritating effects towards mucous membranes; MTT cytotoxicity test with 3T3 fibroblasts; human corneal epithelial models to investigate inflammatory mediators and cytotoxicity; macrophage assays to measure cytotoxicity, inflammatory mediators and oxidative stress. Together with results from clinical studies, exposure estimates and analyses of kinetic properties, the presented information provides sound evidence to support the safe use of HPC. This is an example of a risk assessment for cosmetic use of small particles without the need for additional animal studies.     

Amorphous Water-Soluble Cyclodextrin Derivatives: 2-Hydroxyethyl, 3-Hydroxypropyl, 2-Hydroxyisobutyl,and Carboxamidomethyl Derivatives of β-Cyclodextrin

The pharmaceutical usefulness of natural, crystalline cyclodextrins can be improved by chemical conversions into water-soluble, amorphous mixtures of their derivatives. Reaction of -cyclodextrin with 2-chloroethanol, 3-chloropropanol, isobutylene oxide, or iodoacetamide yielded the title compounds. Distributions of the substitution degree were close to symmetrical and relatively narrow. The average substitution degrees increased with the amount of alkylating reagent used in the preparation. The number of components (half-width of distribution) increased with increasing average substitution degree. Further, distributions of the substitution degree were measured in glucose derivatives after hydrolysis of 2-hydroxyethyl, 2-hydroxypropyl, and 2-hydroxyisobutyl--cyclodextrin. The results show an uneven distribution of substitutents around the cyclodextrins, suggesting that growth of oligoglycol side chains and/or clustering of substituents on one glucose residue occurs.     

火绒草中总黄酮的纯化工艺优选

目的:优选火绒草中总黄酮的大孔吸附树脂富集纯化工艺.方法:采用静态吸附/解吸与动态吸附/解吸相结合的方法,用紫外-可见分光光度法测定火绒草中总黄酮含量,筛选最佳大孔吸附树脂,并对其纯化工艺进行优选.结果:确定采用HPD100型大孔吸附树脂对火绒草中总黄酮进行富集纯化,其最佳工艺条件为以2 BV火绒草供试品溶液(生药质量浓度0.1 g·mL-1)为最大上样量,吸附速率为1 BV·h-1,吸附2h,洗脱流速4 BV·h-1,5 BV水洗脱,4 BV 30％乙醇洗脱,3 BV 50％乙醇洗脱,收集洗脱液,减压浓缩,即得.按上述最佳纯化工艺总黄酮洗脱率＞90％.结论:该优选工艺稳定可行,适合工业化生产.     

HPLC法同时测定五维赖氨酸口服溶液中4种水溶性主成分的含量

目的:建立直接同时测定五维赖氨酸口服溶液中盐酸赖氨酸和三种水溶性维生素含量的RP-HPLC法。方法:采用Phenomenex Gemini C₁₈ 100A(4.6 mm×250 mm, 5μm)色谱柱，以0.03 mol·L^-1磷酸二氢铵溶液(pH 3.0)-甲醇(98∶2)为流动相，检测波长为205 nm,流速1.0 mL·min^-1。结果:盐酸赖氨酸、维生素C、维生素B₆和烟酰胺分别在30.56～488.9μg·mL^-1(r=1.000 0)、24.86～397.8μg·mL^-1(r=0.999 8)、1.018～16.29μg·mL^-1(r=1.000 0)、10.72～171.5μg·mL^-1(r=0.999 0)范围内与峰面积呈良好的线性关系；定量限分别为10.39、0.466 1、0.092 79、0.136 2 ng;平均回收率分别为100.6%、98.5%、98.0%、99.2%,RSD分别为0...     

基于斑马鱼模型的水溶性姜黄素制剂抗血栓和抗炎活性研究

目的 基于斑马鱼模型探究水溶性姜黄素制剂对血栓形成和炎症消退的作用。方法 随机挑选受精后3 d的斑马鱼分为对照组、模型组、阳性药对照组、水溶性姜黄素制剂（姜黄素质量分数为10%，125、250、500、1 000、2 000 μg·mL^-1）组、普通姜黄素（姜黄素质量分数为95%，125、250、500、1 000、2 000 μg·mL^-1）组，每组30尾。除对照组外，其余组使用花生四烯酸、脂多糖、五水合硫酸铜分别诱导建立血栓、细菌性炎症和神经性炎症模型。通过观察分析斑马鱼红细胞染色强度和炎症部位中性粒细胞个数来评价水溶性姜黄素制剂抑制血栓形成和抗炎作用。结果 与对照组比较，模型组斑马鱼心脏红细胞染色强度明显减少（P<0.001）、炎症部位中性粒细胞个数明显增多（P<0.001）；与模型组比较，水溶性姜黄素制剂≥250 μg·mL^-1质量浓度时能显著抑制血栓形成、消退炎症，主要表现为斑马鱼心脏红细胞染色强度显著升高（P<0.001）、炎症部位中性粒细胞个数明显减少（P<0.05、0.01、0.001）；姜黄素在≥1 000 μg·mL^-1时能显著抑制血栓形成（P<0.01、0.001），≥500 μg·mL^-1时能显著消退炎症（P<0.05、0.01、0.001）。姜黄素为水溶性姜黄素制剂给药浓度2～8倍的条件下，才能达到相同的抑制血栓和炎症形成的效果。结论 与普通姜黄素组比较，在相同给药浓度下，水溶性姜黄素制剂具有更好的抑制血栓形成和抗炎作用。     

A Mechanistic Study on the Hydrolysis of Cyclic Ketene Acetal (CKA) and Proof of Concept of Polymerization in Water

The present work systematically investigates the hydrolysis mechanism of cyclic ketene acetal (CKA) monomers in detail and explores polymerization in water under organic solvent-free and surfactant-free conditions. To understand the effect of CKA structure on hydrolysis, the ring size of the monomers is varied from 5–8-membered rings systematically and hydrolysis experiments are performed. In all cases, hydrolysis yields monoacetylated diol products. Deuterium and ¹⁷O-isotopic labeled experiments are carried out for 5- and 7-membered-(2-methylene-1,3-dioxepane, MDO) CKAs to understand the reaction pathway. The experimental analysis from the reaction of CKA with water revealed that the increasing hydrophobicity from 5–8-membered rings and the pH of the reaction medium play important roles in the order of reactivity. Density functional theory (DFT) and experimental studies demonstrated that basic reaction conditions have some control over the hydrolysis rate of CKA. Despite this progress, achieving controlled polymerization of CKA in water while suppressing hydrolysis remains challenge. Only up to 3 mol% CKA incorporation is attained in polyacrylate and polyacrylamide backbone via radical ring-opening polymerization (rROP) of MDO and 8-membered CKAs with 2-hydroxyethyl acrylate (HEA) and acrylamide (AAm) in water. The results serve a proof of concept for advancing aqueous copolymerizations using CKA monomers.