泽泻化学成分及药理作用研究进展

泽泻为我国传统中药,广泛应用于中医临床复方及多种中成药中。目前从泽泻中分离到了220余个化合物,包括三萜、倍半萜、二萜、糖类、含氮化合物、苯丙素、黄酮、甾体等。药理学研究表明泽泻醇提物、水提物及一些单体类成分具有利尿、抗结石及肾脏保护、降血脂及保肝、降血糖、抗癌、抗氧化损伤、抗炎、抗补体等作用。该文对近五十年来泽泻的化学成分和药理作用进行了全面系统的整理,以期为泽泻的深入研究和开发利用提供理论依据。     

不同氢溴酸右美沙芬口服固体制剂的溶出度考察

目的：对6个厂家不同氢溴酸右美沙芬口服固体制剂进行体外溶出度考察，比较体外溶出情况，为临床用药提供参考。方法：采用转篮法，转速100 r·min^-1，用高效液相色谱法测定氢溴酸右美沙芬口服固体制剂在0.1 mol·L^-1盐酸溶液中的溶出曲线；以威布尔方程拟合溶出参数T₅₀、T_d、m，并对参数进行方差分析。结果：氢溴酸右美沙普通片、分散片、胶囊以及软胶囊的平均累积溶出度分别为94.3%、101.3%、105.2%、93.4%。溶出参数T₅₀、T_d差异较大，其中T₅₀最大的是最小的13.4倍。结论：氢溴酸右美沙片、分散片、胶囊以及软胶囊体外溶出行为差别大，产品质量存在较大差异。     

Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.     

水分去除的方法及其在药物合成中的应用

化学药合成过程中水分残留不利于反应的进行,还影响药物及制剂的稳定性、理化性质、溶出及药理作用等,因此水分几乎是大多数药物合成中的必测项目,通过有效除水严格控制反应体系中水分的含量至关重要。本文综述了水分的存在形式,常见除水剂和脱水剂的种类、作用原理与除水能力,以及在药物合成的应用,为药物合成反应中水分的去除提供参考。     

Fast CT-PRESS-based spiral chemical shift imaging at 3 Tesla.

A new sequence is presented that combines constant-time point-resolved spectroscopy (CT-PRESS) with fast spiral chemical shift imaging. It allows the acquisition of multivoxel spectra without line splitting with a minimum total measurement time of less than 5 min for a field of view of 24 cm and a nominal 1.5x1.5-cm2 in-plane resolution. Measurements were performed with 17 CS encoding steps in t1 (Deltat1=12.8 ms) and an average echo time of 151 ms, which was determined by simulating the CT-PRESS experiment for the spin systems of glutamate (Glu) and myo-inositol (mI). Signals from N-acetyl-aspartate, total creatine, choline-containing compounds (Cho), Glu, and mI were detected in a healthy volunteer with no or only minor baseline distortions within 14 min on a 3 T MR scanner.     

Modeling in Frequency Domain Used for Assessment of In Vivo Dissolution Profile

Purpose. To present a model-dependent approach for the assessment of the in vivo drug dissolution profile based on in vitrodata for the multiple unit dosage form, as an alternative to the numerical method proposed in the study by Hayashi et al, Pharm. Res. 12:1333–1337 (1995). Methods. The data for aspirin granules administered to healthy subjects obtained in the above mentioned study were re-evaluated. The subject dissolution system was considered to consist of two subsystems connected in series, i.e. the subsystem describing the gastric-emptying process and the subsystem describing the intestinal dissolution process. The frequency response method was used to model the subject dissolution system. Results. The model in vivodissolution profile of aspirin, assessed as the integral of the model weighting function of the subject dissolution system, was in agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method. Conclusions. Comparison of dynamic properties of the subject dissolution system with the subsystem describing the gastric-emptying process yielded quantitative confirmation of the decisive role of the gastric-emptying process in the in vivodrug dissolution after administration in the multi unit dosage form.     

C60的化学反应性和高分子化

综述了C_(60)化学研究的进展。C_(60)的化学反应性的研究展现了一个广阔的新领域,并使C_(60)作为一种新型的功能基团引入高分子成为现实。这些进展为进一步深入研究C_(60)尤其是C_(60)的材料化提供了前提。     

尼罗罗非鱼肉营养成分分析

<正> 尼罗罗非鱼(Tilapia nilotica)是我国从非洲引进的热带鱼类,具有刺少肉味鲜嫩、食性广、生长快、繁殖力强、养殖周期短等特点。已快速地养殖到全国各地。作者对利用地热资源人工喂养条件下的尼罗罗非鱼肉的氨基酸和肉内的粗蛋白、脂肪、维生素等成分进行分析,评估尼罗罗非鱼肉的营养价值,从营养学的角度为人们提供科学依据。     

人血清白蛋白修饰的尿激酶与天然尿激酶的家兔体内过程比较

家兔静注人血清白蛋白修饰的尿激酶(MUK)和天然尿激酶(NUK)40000IU后,MUK 的体内过程符合零级速率过程,NUK 则符合一级速率过程,血纤溶活性 MUK 持续100min,而 NUK 仅20～25min。在“功能性”去除肝肾的家兔,NUK 血浓度半衰期延长3～4倍,而 MUK 血浓度下降与正常家兔相似。MUK 及 NUK 在去除纤溶抑制物的优球蛋白成份中纤溶活性相似,但在血浆中 NUK 仅存24～35%的纤溶活性,MUK 则保留了64～85%的纤溶活性。提示肝肾的摄取、代谢和消除能力降低及对血浆纤溶抑制物抵抗力增强,是 MUK 血纤溶活性长时间维持高水平的主要原因。     

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.