复方氯己定含漱液预防干槽症临床观察

目的:评价复方氯己定含漱液预防下颌阻生智齿拔除术后干槽症的临床效果。方法:临床搜集需拔除下颌阻生智齿的342例患者,共342颗牙,随机分为复方氯己定含漱液组(A组)、口服抗生素组(B组)和消炎抗菌可溶止血纱布组(C组),比较3组术后干槽症的发病率。结果:A组干槽症发病率显著低于C组(P<0.05);A组与B组、B组与C组间比较,干槽症发病率均无显著性差异(均P>0.05)。结论:下颌阻生智齿拔除后,口腔应用复方氯己定含漱液可有效预防术后干槽症的发生。     

CYP2D6 variation,behaviour and psychopathology: implications for pharmacogenomics-guided clinical trials

Individual and population differences in polymorphic cytochrome P450 enzyme function have been known for decades. The biological significance of these differences has now been deciphered with regard to drug metabolism, action and toxicity as well as disposition of endogenous substrates, including neuroactive compounds. While the cytochrome P450 enzymes occur abundantly in the liver, they are expressed in most tissues of the body, albeit in varying amounts, including the brain. The latter location of cytochrome P450s is highly pertinent for susceptibility to neuropsychiatric diseases, not to mention local drug metabolism at the site of psychotropic drug action in the brain. In the current era of personality medicine with companion theranostics (i.e. the fusion of therapeutics with diagnostics), this article underscores that such versatile biological roles of cytochrome P450s offer multiple points of entry for personalized medicine and rational therapeutics. We focus our discussion on CYP2D6, one of the most intensively researched drug and endogenous compound metabolism pathways, with a view to relevance for, and optimization of, pharmacogenomic-guided clinical trials. Working on the premise that CYP2D6 is related to human behaviour and certain personality traits such as serotonin and dopamine system function, we further suggest that the motivation of healthy volunteers to participate in clinical trials may in part be influenced by an under-or over-representation of certain CYP2D6 metabolic groups.     

Modeling of activity landscapes for drug discovery

Introduction: Activity landscapes (ALs) are graphical representations that integrate compound structure and potency relationships. These computer-generated models enable the interactive large-scale analysis of structure–activity relationships (SARs) and complement traditional approaches to study SARs of individual compound series in a qualitative or quantitative manner. A variety of AL designs have been reported.

Areas covered: The concept of activity landscapes is introduced and different methodologies to represent 2D or 3D AL representations of large compound data sets are described on the basis of original literature references. Several AL variants and extensions have been generated for special applications in medicinal chemistry. These include, for example, AL views of evolving data sets with constant topology, selectivity landscapes and multi-target ALs, or molecular mechanism and multi-property maps. Furthermore, the applicability domain of the AL concept is discussed including specific requirements for practical utility in medicinal chemistry opportunities for further developments.

Expert opinion: AL modeling has substantially extended conventional ways to study SARs. The AL concept is inseparable from the notion of activity cliffs that are of high interest in SAR analysis. AL design is an area of active research at the interface between chemoinformatics and medicinal chemistry with potential for further growth. Special emphasis must be put on increasing the usability of AL models for practicing medicinal chemists.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

加用复方龙星片治疗感冒后咳嗽的临床研究

[目的] 通过用复方甲氧那敏胶囊和加用复方龙星片的方法分别治疗感冒后咳嗽,观察两组的临床疗效。[方法] 将符合入组条件的80例患者在服用复方甲氧那敏胶囊(商品名:诺尔彤)的基础上,采用随机数字表法随机分为常规治疗组(对照组)40例,加用复方龙星片组(治疗组)40例,服药14 d为1个疗程。[结果] 治疗组临床总有效率为90.00%,对照组为80.00%,两组在总体疗效上差异有统计学意义(P<0.05);治疗组在日间咳嗽、夜间咳嗽、咳痰量、咽痒、喘息的改善情况要好于对照组,差异有统计学意义(P<0.01);而两组在气短的症状改善上差异无统计学意义(P>0.05);治疗组的起效时间快于对照组;治疗后两组的生活质量评分比治疗前都有了很大的提高,而治疗组提高明显高于对照组,两组间的差异有统计学意义(P<0.05)。[结论] 经加用复方龙星片治疗感冒后咳嗽疗效明显优于对照组。     

法匹拉韦的合成

目的：设计并探索一条工艺稳定、收率较高的抗病毒化合物法匹拉韦（T-705）的合成工艺路线。方法以氨基丙二酸二乙酯盐酸盐为起始原料,氨水氨解后与乙二醛环合得到3-羟基-2-吡嗪酰胺、经硝酸钾硝化后制得3-羟基-6-硝基-2-吡嗪酰胺,再经三氯氧磷氯代、氟化钾氟代制得3,6-二氟-2-氰基吡嗪,水解成盐,最后经过氧化氢（双氧水）氧化制得目标化合物法匹拉韦。结果设计出的合成路线能有效制备目标化合物。结论该合成路线各步反应中除氟取代需要严格去水外,其余各步反应条件较温和且操作简单、收率稳定,适合规模制备。     

大黄贴敷联合复方聚乙二醇电解质散口服对便秘患者肠道准备给药时机的影响

目的探讨大黄贴敷神阙穴和天枢穴联合口服复方聚乙二醇电解质散(PGEP)在便秘患者肠道准备中的给药时机。方法选择行结肠镜检查的便秘患者300例,分3组,各100例。A组检查前1天晚上9点,行中药贴敷神阙穴和天枢穴,检查当天早上5~7点服完PGEP 139.12 g(2 000 ml);B组检查前1天晚上9点行中药贴敷神阙穴和天枢,检查当天上午10~12点服完相同剂量的PGEP;C组检查当天早上5点行中药贴敷神阙穴和天枢穴,早上5~7点服完相同剂量的PGEP。服药后4 h行结肠镜检查。应用Boston肠道准备量表(BBPS)评分,并对肠腔内气泡进行评分,比较3组患者肠道准备有效性、耐受性及安全性。结果 A组的肠镜检查时间(7.25±0.60)min明显短于B组(9.10±0.80)min和C组(10.50±0.55)min;A组的BBPS评分(8.50±0.35)分明显高于B组(7.35±1.25)分和C组(6.65±1.30)分;A组的肠腔内气泡评分(0.25±0.15)分明显低于B组(0.75±0.65)分和C组(0.55±0.50)分;A组肠道准备接受率、再次肠道准备接受率(96.00%、93.00%)明显高于B组(85.00%、70.00%)和C组(90.00%、88.00%);A组的总体不良反应评分(1.45±0.04)分明显低于B组(1.75±0.55)分和C组(1.60±0.25)分。差异均有统计学意义(P0.05)。结论检查前1天晚上9点大黄穴位贴敷联合检查当天早上5~7点口服PGEP对便秘患者行结肠镜检查肠道准备效果好。     

复方川芎滴丸制备工艺再探讨

目的优选复方川芎滴丸的最佳制备工艺。方法以药物与基质的配比、滴制温度、冷却液的温度为考察因素,采用正交试验设计,以滴丸的圆整度、丸重差异、溶散时限、外观质量的综合评分为评价指标,优选滴丸的成型工艺;以滴距、滴速为考察因素,优选最佳滴制工艺。结果滴丸制备的最佳条件为药物中间体与基质配比12,滴制温度80℃,冷却剂温度15~20℃,滴距5cm,滴速40gtt/min。结论该制备工艺合理,简便,易于控制,适用于本制剂的制备。     

HPLC测定复方氨肽素片中氨茶碱与马来酸氯苯那敏的含量及含量均匀度

目的 建立HPLC测定复方氨肽素片中氨茶碱与马来酸氯苯那敏的含量及含量均匀度。方法 色谱柱为YMC Hydrosphere C₁₈(4.6 mm×250 mm,5 μm),流动相为乙腈-0.5%磷酸溶液(用三乙胺调pH值至2.2)(10∶90),流速为1.0 mL·min^-1,柱温为30 ℃,检测波长为262 nm。结果 茶碱和马来酸氯苯那敏分别在0.06~0.58 mg·mL^-1和2.2~20.0 μg·mL^-1内线性关系良好,回收率分别为100.4%和101.2%,RSD分别为0.74%和1.40%(n=9)。结论 方法快速准确,重复性好,结果可靠,可同时测定氨茶碱及马来酸氯苯那敏,为产品质量标准提高提供基础。