中药血清药理学研究金银花的抑菌活性

采用最低抑菌浓度(MIC)测定方法和抑菌活性试验,考察不同产地的金银花以及含药血清的抑菌效果。试验结果为:含药血清对大肠杆菌和金黄色葡萄球菌的MIC分别为0.5μg绿原酸/mL和0.25μg绿原酸/mL;含药血清抑菌活性为高敏。     

化合物库的组合技巧和组合合成

从化合物库的组合技巧和组合合成方法两个方面探讨了组合化学及其在药物开发中的应用。     

The identification of tricyclic neuroleptics and sulphonamides by high-performance thin-layer chromatography

Circular high-performance thin-layer chromatography (HPTLC) has been used to differentiate a series of twelve tricyclic neuroleptics, using both normal phase and reverse phase procedures. The use of normal phase systems also allows the resolution of geometric isomers of chlorprothixene, clopenthixol and flupenthixol. Thirteen sulphonamides and Trirnethoprim may also be distinguished using HPTLC.     

配糖蛋白B—阳离子丙烯酸树脂微胶囊的性能研究

本文研究了配糖蛋白B-阳离子丙烯酸树脂微胶囊的形态、粒径及粒径分布,并在模拟胃液的酸性缓冲液中进行了微胶囊的溶解释放试验。结果表明该微胶囊能溶于人体的胃液中,可配制适合儿童口服的混悬剂。     

Preparation and characterisation of thermoresponsive poly[(N-isopropylacrylamide-co-acrylamide-co-(hydroxyethyl acrylate)] microspheres as a matrix for the pulsed release of drugs

Despite the large number of publications and patents concerning pH/thermoresponsive polymers, few data are available concerning the preparation of thermoresponsive cross-linked microspheres from preformed polymers. Therefore, N-isopropylacrylamide-co-acrylamide-co-(2-hydroxyethyl acrylate) copolymers were obtained as a new thermoresponsive material with a lower critical solution temperature (LCST) around 36 degrees C, in phosphate buffer at pH 7.4, and with a cross-linkable OH group in their structure. The LCST value was determined both by UV spectroscopy and microcalorimetric analysis. These copolymers were solubilised in acidified aqueous solution below their LCST, dispersed in mineral oil, and transformed into stable microspheres by cross-linking with glutaraldehyde. The thermoresponsive microspheres were characterised by optical and scanning electron microscopy, degree of swelling, and water retention. The pore dimensions of the microspheres and the retention volumes of some drugs and typical compounds were evaluated at different temperatures by liquid chromatography. Indomethacin, as a model drug, was included in the microspheres by the solvent evaporation method. Finally, the influence of temperature and of temperature cycling on drug release was investigated.     

Open-access liquid chromatography/mass spectrometry in a drug discovery environment

The use of open-access mass spectrometry to monitor synthetic chemistry reactions, and also the integrity and purity of new chemical entities, has been a part of the medicinal chemist's tool-box for more than 5 years. Originally in our group at Wyeth Research there were two open-access methods available to the chemists, flow injection analysis (FIA) and liquid chromatography/mass spectrometry (LC/MS). The FIA method was approximately 3 min long, while the LC/MS method was approximately 20 min long (including an 8 min gradient). Within the first 2 years, the total number of open-access analyses increased by approximately 125%. It is interesting, however, that the number of LC/MS analyses increased by more than 285%. This is attributed to the fact that the chemists began using the LC/MS data to monitor reactions and also to check final product integrity and purity. In addition, the number of chemists performing parallel synthesis reactions has increased; thus, individual chemists can produce sample sets of up to 100 vials. This paper describes the implementation of new methodology, which accommodates the need for much faster run times and also the ability to acquire alternating positive and negative ion spectra within the same run. In addition, the instrument has been configured to e-mail the resulting processed data report to the submitting chemist. Several methods have been developed, including structure elucidation using in-source collision-induced dissociation (CID) and night-time analysis. The LC/MS methods for this system are described herein and are applicable to both industrial and academic synthetic chemistry optimization efforts.     

Polyelectrolyte capsules made of two biocompatible natural polymers

In this study the influence of the experimental conditions on the obtention of polyelectrolyte multilayer capsules was investigated. Two ways of the simple coacervation method was used to obtain spherical capsules involving chitosan and hyaluronan, chitosan being inside the particle covered by a hyaluronan layer to increase the biocompatibility. The ¹H-NMR spectroscopy confirmed a polyelectrolyte complex formation and the optical microscopy shows that the complexed capsules have good sphericity with average diameters ranging from 590 at 1550 μm in the experimental conditions adopted. One can observe that in the acid medium the complexed capsules are much stable than the chitosan beads. The structures described provide a starting point for the design and fabrication of complexed capsules made of two biocompatible natural polymers with potential applicability in medical or pharmaceutical applications. Few diffusion experiments demonstrated that the complexed layer controls the diffusion of dextran included in the chitosan inner domain.     

Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design,synthesis and biological evaluation

A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain.     

New antimalarial drugs

Approximately 40% of the world population live in areas with the risk of malaria. Each year, 300-500 million people suffer from acute malaria, and 0.5-2.5 million die from the disease. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise. The most important reason for this alarming situation is the rapid spread of malaria parasites that are resistant to antimalarial drugs, especially chloroquine, which is by far the most frequently used. The development of new antimalarial drugs has been neglected since the 1970s owing to the end colonialism, changes in the areas of military engagement, and the restricted market potential. Only in recent years, in part supported by public funding programs, has interest in the development of antimalarial drugs been renewed. New data available from the recently sequenced genome of the malaria parasite Plasmodium falciparum and the application of methods of modern drug design promise to bring significant development in the fight against this disease.     

Polymer dispersions from catalytic polymerization in aqueous systems

By contrast to traditional free radical emulsion polymerization, catalytic polymerization allows for polymer microstructure control. In terms of polymerizable monomers, both techniques are largely complementary. Since the beginning of this decade, an increasing number of reports on polyolefin, polybutadiene, polyalkenamer, polynorbornene, polyketone, and polyacetylene dispersions prepared by catalytic polymerization in disperse aqueous systems has appeared. This contribution reviews the preparation of these dispersions, their colloidal properties, particle formation mechanisms, particle morphologies, and polymer microstructures.