复方制剂中双羟萘酸噻嘧啶及阿苯达唑含量测定方法的研究

本文采用双波长法分别测定驱虫药复方制剂的有效成份双羟萘酸噻嘧啶及阿苯达唑，进行了方法学研究、线相关系、加样回收等实验工作，两种效成分的回收率分别为１００．６±０．６８％，９９．２７±０．５９％（ｎ＝２），含量在其标示量的±２０％范围内线性关系良好，分别为ｒ＝０．９９９９，ｒ＝－９９９８。     

HPLC法测定双羟萘酸曲普瑞林中残留的三氟乙酸

目的建立新型混合模式色谱柱高效液相色谱法测定双羟萘酸曲普瑞林中三氟乙酸含量,并进行样品测定。方法采用Thermo Acclaim Mixed-Mode WAX-1(150 mm×4.6 mm,5μm)色谱柱;流动相:0.25 mol·L^-1磷酸二氢钠溶液(用6 mol·L^-1NaOH溶液调节p H值至6.0)∶乙腈(60:40);柱温:30℃;流速:1.0 mL·min^-1;检测波长:210 nm。结果空白溶剂及供试品中其他组分不干扰三氟乙酸测定,三氟乙酸在0.026~0.080 mg·mL^-1范围内线性关系良好,回归方程为:y=1104.3460x-0.6811,r=0.9998;定量下限为0.8μg;加样平均回收率为98.7%,RSD为1.1%;准确度高;具有良好的重复性;样品中未检出三氟乙酸。结论本方法准确、专属、耐用,可用于双羟萘酸曲普瑞林中三氟乙酸残留的测定。     

双羟萘酸噻嘧啶(噻嘧啶）

本品为(E)-1-甲基-2-[2-(2-噻吩基)乙烯基]1,4,5,6-四氢嘧啶4.4''-亚申基-双(3-羟基2-察酸)盐。按干燥品计算,含C₁₁H₁₄N₂S·C₂₃H₁₆O₆应为97.0~103.0%。     

双萘羟酸噻嘧啶(抗虫灵)

〔论学名〕反式-1-甲基-2-〔2-(2-噻吩基)-乙烯基〕-1,4,5,6-四氢嘧啶·4,4’-甲撑-双-(3-羟基-2-荼酸) 〔结构式〕     

奥氮平双羟萘酸盐长效注射剂体外溶出度的测定

目的：建立奥氮平双羟萘酸盐长效注射剂的体外溶出度方法。方法：采用HPLC法测定奥氮平双羟萘酸盐长效注射剂的溶出度,采用浆法测定药物溶出度,溶出介质为0.5%十二烷基硫酸钠（SLS）模拟肌液（p H 7.0±0.05）,体积为500 ml,分别考察不同转速（25,50,75 r·min^-1）对自制制剂溶出行为的影响。结果：双羟萘酸在2.15-107.40 mg·L^-1（r=0.999 9）内,奥氮平在1.75-87.40 mg·L^-1（r=0.999 9）内浓度与峰面积呈良好的线性关系。奥氮平双羟萘酸盐的平均回收率为99.80%（RSD=0.55%,n=9）;自制制剂和原研制剂在溶出介质中溶出度相似因子f2为70.80。结论：溶出度测定方法能够有效控制该奥氮平双羟萘酸盐长效注射剂的产品质量。     

羟桂皮酸衍生物的抗突变作用

从天然植物中发现多种抗致癌物和抗致突变物,可在多个环节干扰致癌过程,阻断癌症的发生。本文报道存在于天然植物中的羟桂皮酸衍生物邻香豆酸、对香豆酸、咖啡酸及香豆素对细菌SOS反应、大鼠肝微粒体脂质过氧化的体外抑制和对环磷酰胺致小鼠骨髓微核和精子畸形的影响。     

葡萄糖酸锌咀嚼片的制备及质量控制

目的：建立葡萄糖酸锌咀嚼片的制备及质控方法。方法：选用甘露醇为稀释剂、阿斯帕坦为矫味荆、薄荷油为芳香剂、微粉硅胶为助流剂、硬脂酸镁为润滑剂、2％HPMC—E50为粘合剂,其含量测定方法采用络合滴定法。结果：制得的葡萄糖酸锌咀嚼片口感好、表面光滑美观、色泽均匀、硬度适中、服用方便。结论：本制剂处方工艺成熟,检测方法简便、准确、适用于医院制备和应用。     

噻洛芬酸的合成

噻吩经丙酰化得到2-丙酰噻吩，在碘和氧化亚铜催化下进行噻吩基1，2-迁移后水解制得关键中间体2-（2-噻吩基）丙酸，再与苯甲酰氯经Friedel-Crafts反应制得非甾体消炎镇痛药噻洛芬酸，总收率44．6％。     

阿莫西林克拉维酸钾咀嚼片治疗急性细菌感染的疗效

目的：评价阿莫西林克拉维酸钾咀嚼片（8：1）治疗各种急性细菌感染的有效性和安全性。方法：采用随机、双盲、多中心、平行对照临床试验的方法，共纳入病例204例，试验组102例，给予阿莫西林克拉维酸钾咀嚼片（8：1）2片，bid，同时服用阳性对照药模拟剂2片，tid。对照组102例，给予阿莫西林克拉维酸钾咀嚼片（4：1）2片，tid，同时服用试验药模拟剂2片，bid，疗程均为7～14d。结果：试验组和对照组的痊愈率分别为83.33％（85／102）和76.47％（78／102），有效率分别为92.16％（94／102）和89.22％（91／102），两组细菌清除率均为90.70％，阴转率均为84.71％。两组不良反应发生率分别为5.17％（6／116）和9.48％（11／116），以上结果两组组间比较均无统计学意义。结论：阿莫西林克拉维酸钾咀嚼片（8：1）治疗各种急性细菌感染的疗效确切，安全性好。     

氨噻肟酸乙酯的合成

4-氯-3-氧代丁酸乙酯经肟化、与硫脲环合制得2-（2-氨基-4-噻唑基）-2-羟基亚胺基乙酸乙酯，在相转移催化剂溴化四乙铵作用下用硫酸二甲酯醚化制得氨噻肟酸乙酯，总收率46％。     

HPLC测定复方阿苯达唑片的含量

目的　用HPLC法测定复方阿苯达唑片中阿苯达唑和双羟萘酸噻嘧啶的含量。方法　采用硅胶柱 ,以乙腈 -混合液[水 -乙酸 -二乙胺 (2 .5∶2 .5∶1) ](5 4∶1)为流动相 ,检测波长 2 88nm。结果　阿苯达唑的线性范围为 0 2～ 0 6 μg ,回归方程为 :Y =1.832× 10 6X +7.2 84× 10 3 (r=0 .9998) ;双羟萘酸噻嘧啶的线性范围为 0 .8～ 2 .4 μg ,回归方程为 :Y =1 2 5 5× 10 6X -1 736× 10 4(r=0 .9995 )。结论　所用方法简便、快速 ,准确、可靠。     

Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects

Drugs that are largely restricted to the gastro-intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High-performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 ± 9.37, 35.89 ± 8.94, and 36.22 ± 10.10 ng mL^?1 were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The mean t_max values were 2.02 ± 0.12, 2.05 ± 0.356, and 2.05 ± 0.339 h respectively for the above dosage forms; the respective AUC_0–9 values were 81.01 ± 12.97, 94.59 ± 17.18, and 101.47 ± 19.59 h ng mL^?1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter-subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two out of 27 treatments).     

The detection of chemical impurities by high pressure liquid chromatography and the genetic activity of medical grades of pyrvinium pamoate inSaccharomyces cerevisiae andSalmonella typhimurium

The genetic activity of several medical grades of the anthelmintic drug pyrvinium pamoate, which is a dipyrvinium salt, was studied in a diploid mitotic recombination and gene conversion assay (strain D5 ofSaccharomyces cerevisiae), and in several haploid yeast reversion assays (strains XV185-14C, XY718-1A, and 7854-1A). All of the samples were recombinogenic in strain D5 and mutagenic in the haploid strains, however, the degree of genetic activity varied considerably among the medical grades of pyrvinium pamoate that were tested. Similarly, these samples varied in degree of mutagenicity when they were tested in strains TA97, TA98, TA100, and TA102 ofSalmonella typhimurium, but some of the medical grades of pyrvinium pamoate were mutagenic both in the presence and in the absence of the metabolic transformation system, whereas other medical grades of the drug required such activation to be mutagenic. In addition, the medical grades and dosage forms of several brands of pyrvinium pamoate were examined for purity by fluorescence high pressure liquid chromatography (HPLC) using a methanol:water (9010) solvent system. The HPLC data indicate that monopyrvinium salts are the major contaminants in these pharmaceuticals. In general, there is a correlation between the degree of genetic activity and toxicity, and the number and relative quantity of impurities found in each sample.     

Preparation and evaluation of release characteristics of 3TabGum, a novel chewing device

A new chewing gum device in the form of a three layers tablet (3TabGum) has been developed. The new drug delivery system is obtained, at room temperature, by direct compression using conventional pharmaceutical equipment. Basically, the resulting chewing gum tablets comprise a gum core combined with two protective antiadherent external layers, which prevent gum adhesion to the punches of the tableting machine. Drug release from a dosage form is the critical step in drug absorption and bioavailability, thus an experimental protocol has been designed to evaluate the efficiency of this kind of therapeutic system by verifying its capability to release the drug dose and by assessing the delivery rate. Simple diffusion into the medium causes the release of only a small percentage of the drug contained in the medicated chewing gum, while the delivery of the major part of the dose occurs during mastication. The results obtained in this study suggest that water soluble drugs are freely and easily released by chewing gums, while for actives characterized by reduced water solubility the release rate depends on the chewing time although all the drugs tested are completely released after a reasonable mastication time.     

脉通胶囊药效学实验研究

目的 通过不同的实验方法和动物模型对脉通胶囊的功能进行验证,为临床合理用药提供依据.方法 采用注射胶原蛋白-肾上腺素诱导剂后记录各组小鼠5 min内死亡数和15 min内发生的偏瘫数,观察其体内抗血栓作用;采用大鼠体外血栓形成实验的方法,观察其体外抗血栓作用;采用测定角叉菜胶所致大鼠足趾肿胀度的方法,观察其抗炎作用;采用记录注射醋酸后各组小鼠第一次扭体反应出现时间及15 min内扭体次数的方法,观察其镇痛作用.结果 脉通胶囊可明显减少小鼠5 min内死亡数和15 min内出现偏瘫数(P<0.05);可明显抑制大鼠体外血栓形成(P<0.05);可明显减少致炎大鼠足趾肿胀率(P<0.05或P<0.01);可明显延长致痛小鼠第一次扭体发生时间(P<0.05)及明显减少扭体次数(P<0.05).结论 脉通胶囊具有抗血栓、抗炎镇痛作用.     

The effects of nicotine chewing gum on the sensitivity to muscle tension

It has been shown that smoking can alter the sensitivity to muscle activity in female smokers. The present study was designed to assess the effects of smoking cessation and nicotine replacement on sensitivity to muscle tension. Twenty-five women were randomly assigned to one of two groups. One group was given nicotine chewing gum during the withdrawal period and a second group was given no nicotine replacement. Results showed a significant difference in sensitivity at post-test for subjects given nicotine gum compared to subjects receiving no nicotine replacement. These results are consistent with the hypothesis that nicotine alters sensitivity to muscle tension.     

The pharmacodynamics of antiplatelet compounds in thrombosis treatment

Introduction: As it is importance to understand the involvement of platelets in the initiation and propagation of thrombosis, antiplatelet drugs have come to the forefront of atherothrombotic disease treatment. Dual antiplatelet therapy of aspirin plus clopidogrel has its benefits, but it also has its limitations with regard to its pharmacologic properties and adverse effects. For these reasons, within the last decade or so, the investigation of novel antiplatelet agents has prospered.

Areas covered: In this review, we discuss the unique pharmacodynamic properties of several antiplatelet drugs with their possible potential molecular of mechanisms on inhibiting platelet aggregation.

Expert opinion: Considering multiple synergetic pathways of platelet activation and their close interplay with coagulation, the current treatment strategies are not only based on platelet inhibition, they also rely on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current guidelines recommend various antiplatelet agents in addition to aspirin for patients with acute coronary syndromes. The advantages of these agents, as repute mortality, may be associated with off-target effects of the drug. Hence, further studies are required to facilitate the physician’s choice of the most appropriate antiplatelet agents for each patient for thrombosis treatment.     

西尼地平片治疗轻中度高血压的有效性和安全性

目的评价西尼地平治疗轻中度原发性高血压的有效性和安全性。方法用随机双盲对照试验设计,入选病人共48例,西尼地平(试验组)24例,氨氯地平(对照组)24例。结果与治疗前相比,治疗8周后试验组收缩压和舒张压分别下降19.26和14.68mmHg(P<0.01),对照组分别下降为18.22和12.91mmHg(P<0.01),均有统计学意义。试验组和对照组药物不良反应的例数分别为0和2例,2组比较无统计学差异(P>0.05),均无严重不良反应发生。结论西尼地平片每日服用1次,降低血压,安全有效。     

The reality of in-line tablet coating

The possibility of continuous processing in pharmaceutical tablet manufacturing is hampered by the viscoelastic recovery of tablets post-compaction. Compacted tablets are typically aged before coating to allow complete viscoelastic recovery so as to avoid subsequent coating defects. There has been little attempt to overcome tablet recovery in order to enable continuous processing and improve manufacturing efficiency. However, with the introduction of improved or newly developed types of tablet-coating equipment, there is renewed interest in the coating of tablets in-line. In-line tablet coating is defined as the coating of tablets immediately after compaction. It is a one-step highly integrated system that circumvents the delay in processing time typically given to allow viscoelastic recovery of tablets. This review aims to summarize the requirements of an in-line tablet-coating system. The possibility of carrying out in-line tablet coating in the near future will also be discussed.     

The effect of chewing gum on self-reported nicotine withdrawal: Is it the flavor,the act of chewing,or both?

A healthy alternative that has been shown to lessen the severity of nicotine withdrawal symptoms during brief periods of nicotine abstinence (e.g., 3–4 h) is confectionary chewing gum (Cohen and colleagues, 1997, 1999, & 2001). The current study sought to build upon this line of research by examining the impact of chewing gum on nicotine withdrawal severity over an extended period of nicotine abstinence (e.g., 24 h) while also identifying the specific attributes of chewing gum that may be responsible for the reported decreases in withdrawal. Specifically, the acts of chewing, flavor, as well as the combination of the two, were independently examined. Twenty-four dependent cigarette smokers participated in three experimental conditions (e.g., a flavorless gum base, flavor strips, and flavored chewing gum) as well as a no product control across four weeks while abstaining from smoking for 24 h each week. Using repeated measures ANOVAs, a significant difference in withdrawal severity was reported by participants across conditions, F(3, 69) = 2.89, p < .05. Follow-up analyses revealed that the flavored gum condition yielded significantly lower withdrawal scores than the flavorless gum base and no product control conditions. These findings indicate that chewing gum appears useful in lessening the severity of nicotine withdrawal symptoms over a 24-hour period of nicotine abstinence and that it is a combination of flavor and chewing that appears to lead to this effect.