超重运输对路面破坏机理与对策研究

通过对我国目前国道主干线普遍存在超重运输为特征的重载交通现象研究,分析超重运输对路面结构及道路寿命的影响,提出以碳纤维混凝土(CFC)为核心技术的实态超重控制系统,该系统解决了当前超重交通控制难、控制指标定量难的问题。     

棉酚及其衍生物的医药研究进展

本文主要介绍天然植物棉花中的棉酚在医药方面的应用研究 .全文以棉酚及棉酚的衍生物为例在三个方面 (抗生育作用、抗癌作用以及其它方面 )进行综述 .并着重阐述该物质对男性抗生育能力的机理和主要副作用的研究 .     

RNA aptamers as reversible antagonists of coagulation factor IXa

Many therapeutic agents are associated with adverse effects in patients. Anticoagulants can engender acute complications such as significant bleeding that increases patient morbidity and mortality. Antidote control provides the safest means to regulate drug action. For this reason, despite its known limitations and toxicities, heparin use remains high because it is the only anticoagulant that can be controlled by an antidote, the polypeptide protamine. To date, no generalizable strategy for developing drug-antidote pairs has been described. We investigated whether drug-antidote pairs could be rationally designed by taking advantage of properties inherent to nucleic acids to make antidote-controlled anticoagulant agents. Here we show that protein-binding oligonucleotides (aptamers) against coagulation factor IXa are potent anticoagulants. We also show that oligonucleotides complementary to these aptamers can act as antidotes capable of efficiently reversing the activity of these new anticoagulants in plasma from healthy volunteers and from patients who cannot tolerate heparin. This generalizable strategy for rationally designing a drug-antidote pair thus opens up the way for developing safer regulatable therapeutics.     

无机纳米载体在靶向药物输送中的应用研究进展

纳米材料在生物领域的渗透形成了纳米生物材料,而纳米药物载体的研究是纳米生物材料的前沿和热点之一.常见的无机纳米药物载体包括磁性纳米粒子、介孔二氧化硅、纳米碳材料、量子点等,这些无机纳米药物载体在实现靶向性给药、控释和缓释药物以及癌症靶向治疗等方面表现出良好的应用前景.而且,集成像、靶向给药和癌症治疗功能于一身的多功能纳米药物载体比常规化疗药物载体具有明显优势.文中综述了近年来上述无机纳米材料尤其是多功能无机纳米载体在靶向药物输送中的应用及其载药释药行为的研究进展.     

药物中间体p-氨基苯基苄基醚的合成研究

本论文利用微波技术首次成功地实现了 p -氨基苯基苄基醚化合物的合成 ,对 p -硝基苯基苄基醚的还原也进行了有力的探索 ,并得到满意的结果 .总收率达 84.3% .     

Substituted ammonium ions as allergenic determinants in drug allergy

Serious, and occasionally fatal, anaphylactic-like (anaphylactoid) reactions may occur when a patient is exposed to a drug for the first time. Apart from the penicillins, nothing is known of the nature of antigenic or sensitizing drug determinants and, as yet, there is no evidence for the involvement of IgE antibodies in most drug reactions. Muscle relaxants such as alcuronium have been implicated in many life-threatening anaphylactoid reactions but the mechanisms remain unclear. We have now investigated the possibility that drug-specific IgE antibodies are involved by using an alcuronium-carrier complex in a radioimmunoassay with patients' sera. Alcuronium-reactive antibodies were found in five drug-sensitive subjects and most of the antibodies cross-reacted with other muscle relaxants and with a variety of apparently structurally unrelated drugs. Structure-activity studies designed to explore the molecular basis of the antibody binding established that quaternary and tertiary ammonium ions were the complementary allergenic sites on the reactive drugs. These structures occur widely in many drugs but also in foods, cosmetics, disinfectants and industrial materials. Hence, there would seem to be ample opportunity for sensitive individuals to come into contact with and synthesize IgE antibodies to these unusual, and previously unsuspected, antigenic determinants.     

Hierarchical porous calcium carbonate microspheres as drug delivery vector

CaCO3 crystals with different hierarchical structure were fabricated by the precipitation of CaCO3 in an aqueous solution containing guar gum (GG). Through adjusting a range of parameters, the size distribution and microstructure of CaCO3 were well controlled. Results showed that GG facilitated the formation of the hierarchical hollow sphere through assembling of nanocrystals, while inhibited the growth of CaCO3 crystals and restrained phase transition from calcite to vaterite at high concentration of GG (CGG) condition; Moreover, increasing reaction temperature led to larger particles and stable crystalline phase formed. According to the results, a morphology map was presented. Furthermore, Drug loading and releasing results ensured porous CaCO3 microspheres a promising vector for drug delivery.     

抗抑郁症药吗氯贝胺的合成工艺研究

以4-氯苯甲酸为起始原料,经酰胺化、酰氯化和缩合(N-烷基化)三步反应,合成具有抗抑郁症作用的吗氯贝胺。该合成方法具有原料易得、总收率高、对设备要求低和操作简单等优点,具有发展成为适用于工业化大规模生产的潜能。在合成过程中,对每步反应条件进行了优化,在最佳反应条件下总收率达72. 6%。目标产物及中间产物结构都经~1H NMR、~(13)C NMR、MS和元素分析法进行表征。     

Trans-spliced leader RNA exists as small nuclear ribonucleoprotein particles in Caenorhabditis elegans

Maturation of some messenger RNAs in the nematode Caenorhabditis elegans involves the acquisition of a 22-base leader at their 5' ends. This 22-base leader, called the spliced leader (SL), is derived from the 5' end of a precursor RNA of 90-100 bases, called spliced leader RNA (SL RNA). SL RNA is transcribed from a 1-kilobase DNA repeat which also encodes the 5S ribosomal RNA. A subset of mRNAs in C. elegans acquire SL from SL RNA by a trans-splicing mechanism. SL behaves as a 5' exon in the trans-splicing reaction. Using antisera against the Sm antigen that is associated with small nuclear ribonucleoprotein particles (snRNPs), we precipitated SL RNA from extracts of C. elegans, indicating that it is bound by the Sm antigen in vivo. SL RNA also possesses the unique trimethylguanosine (m32,2,7G) cap characteristic of most small nuclear RNAs. Therefore, SL RNA is a chimaeric molecule, made up of an snRNA attached to a 5' exon and is a constituent of a snRNP.     

立方液晶作为药物载体的研究

甘油单油酸酯(MO),嵌段共聚物((PEO)99-(PPO)67-(PF0)99,F127),水立方液晶体系在水中分散可形成立方液晶颗粒分散体系,该分散体系可作为药物缓释的载体、利用原子力显微镜(AFM)和动态激光光散射法测试了立方液晶颗粒的尺寸,分别用紫外分光光度法和高压液相色谱仪测定了甘油单十四烷酸酯(MM)、甘油单十六烷酸酯(MP)、F127以及不同溶剂对立方液晶颗粒包结阿司匹林或咖啡因缓释效率的影响,结果表明：分散体系中加入MP后,可提高阿司匹林的释放效率;而MM的加入则降低药物的释放效率,F127的质量分数达到一定值时,对药物缓释效率有显著的促进作用．制备前体时,使用不同的溶剂,包结药物的释放效率也有所不同。     

反相微乳液制备pH响应型纳米水凝胶及其作为药物载体的研究

利用反相微乳液聚合,通过改变交联剂含量制备不同粒径的纳米水凝胶聚(甲基丙烯酸二甲氨基乙酯-co-甲基丙烯酸羟乙酯)(P(DMAEMA-co-HEMA)).纳米水凝胶的结构和形貌通过FT-IR、1H-NMR和TEM等进行了表征.利用紫外-可见分光光度计(UV)检测溶液在不同pH下的透光率,结果显示纳米水凝胶在酸性条件下有明显的溶胀现象.选取阿霉素(DOX)为模型药物研究了该纳米水凝胶作为药物载体的可行性,结果发现该纳米水凝胶能很好地负载药物,载药率达45.7%.利用紫外光谱法测定载药纳米水凝胶分别在pH 5.0和7.4的溶液中的药物释放行为,结果表明该纳米水凝胶具有较好的pH响应性,在酸性条件下纳米水凝胶的溶胀现象使得药物释放速率比在中性环境下快.