昂丹司琼的合成工艺改进

目的改进昂丹司琼的合成工艺。方法以1,2,3,9四氢4H咔唑4酮经N甲基化、Mannich反应和缩合得止吐药昂丹司琼。结果取得较佳的工艺条件,总收率为43.9%。结论该方法易于工业化生产。     

盐酸昂丹司琼合成工艺优化

目的优化盐酸昂丹司琼的合成工艺。方法以1,2,3,9-四氢-4H-咔唑-4-酮为起始原料,经甲基化得9-甲基-1,2,3,9-四氢-4H-咔唑-4-酮(3),3与二甲胺盐酸盐、多聚甲醛、2-甲基咪唑经过"一锅烩"反应得到中间体9-甲基-3-[(2-甲基-1H-咪唑-1-基)甲基]-1,2,3,9-四氢-4H-咔唑-4-酮(4),4经成盐反应得到目标产物盐酸昂丹司琼。结果与结论目标化合物的结构经1H-NM R、M S谱确证,总收率为57.2%,该合成工艺步骤简便,收率较高,易于工业化生产。     

盐酸昂丹司琼分散片的研制及质量控制

目的 :研究盐酸昂丹司琼分散片的制备方法和质量控制。方法 :采用紫外分光光度法测定主药昂丹司琼的含量。结果 :线性范围为4 0～16 5μg/ml,平均回收率为99 97 % ,RSD为0 35 %。结论 :该制剂制备工艺简单 ,质量可控。     

昂丹司琼用于腹腔镜阑尾切除术患者的观察

目的:探讨在腹腔镜阑尾切除术中应用昂丹司琼预防术后恶心、呕吐的临床效果。方法:选择40例腹腔镜阑尾切除术的患者,麻醉方法相同,随机分为对照组、昂丹司琼组。昂丹司琼组在手术结束时静脉注射昂丹司琼4 mg。双盲法观察术后24小时内恶心、呕吐发生情况及严重程度。结果:术后24小时昂丹司琼组手术后恶心、呕吐(PONV)的发生率明显低于对照组。结论:昂丹司琼用于腹腔镜阑尾切除术能有效预防手术后恶心、呕吐的发生率。     

国产与进口昂丹司琼预防顺氯氨铂所致呕吐的费用效果分析

目的：对进口昂丹司琼（枢复宁）与国产昂丹司琼预防顺氯氨铂所致呕吐的临床疗效与治疗费用进行分析。方法：使用含顺铂化疗方案的肿瘤病人，随机自身对照，交替使用进口和国产昂丹司琼，评价其止呕效果及其安全性，计算每一周期止吐药的总费用。结果：急性止呕有效率进口昂丹司琼组为７０％，国产昂丹司琼组为７５％，在一个治疗周期内，两药的止呕有效率无显著差别。药物不良反应的发生频率也近似且程度较轻，但进口昂丹司琼的费用     

昂丹司琼联合小剂量舒芬太尼预防异丙酚注射痛的临床观察

目的观察昂丹司琼联合小剂量舒芬太尼预处理减轻异丙酚注射痛的临床效果。方法 120例拟行无痛肠镜的患者.随机分为对照组（I组）、舒芬太尼组（Ⅱ组）、昂丹司琼组（Ⅲ组）和昂丹司琼联合舒芬太尼（Ⅳ组）.每组30例。对照组患者给予生理盐水3mL.其它患者按其分组分别给予舒芬太尼0.1μg.kg-1、昂丹司琼4mg或昂丹司琼4mg和舒芬太尼0.1μg.kg-1混合液。30秒后按2mg.kg-1推注异丙酚,同时记录注射部位疼痛评分。结果 4组患者术中异丙酚注射痛发生率分别为：对照组86.7%,舒芬太尼组46.7%,昂丹司琼组40%,昂丹司琼联合舒芬太尼组20%。后3组注射痛发生率低于对照组（P〈0.05）.并且舒芬太尼组和昂丹司琼联合舒芬太尼组异丙酚用量明显少于对照组和昂丹司琼组（P〈0.05）。结论昂丹司琼联合舒芬太尼更好地减轻了异丙酚的注射痛,同时又减少了异丙酚的用量,还能预防术后的恶心、呕吐,是一种较为理想的减轻异丙酚注射痛的临床方法。     

昂丹司琼口腔黏附片的制备及评价

目的 制备及评价盐酸昂丹司琼口腔黏附片.方法 采用相关的黏膜黏着剂卡波姆(CP934)、海藻酸钠、低黏度羧甲基纤维素钠( SCMCLV),用直接压片法压片,对黏附片的不同参数如药物含量,体外溶胀百分率、药物体外释放度和黏附力进行评价.结果 筛选出最佳配方:昂丹司琼5mg、CP934 30 mg、SCMC 165 mg、聚乙二醇-6000 40 mg,乳糖10mg、硬脂酸镁1.5 mg和阿斯巴甜2mg.结论 与昂丹司琼的普通片剂进行比较,昂丹司琼口腔黏附片体外药物释放和渗透都很好,既避免了肝脏首过效应,提高了昂丹司琼的生物利用度;又避免了昂丹司琼的苦味,更易于为患者所接受.     

不同厂家盐酸昂丹司琼片的溶出度考察

目的对3个不同厂家所生产的盐酸昂丹司琼片体外溶出度进行了考察,为临床用药提供参考。方法根据《中华人民共和国药典》(2010版)中盐酸昂丹司琼片的溶出度实验项下要求,采用浆法测定溶出度,紫外-可见分光光度法测定吸光度,对照品法计算溶液中盐酸昂丹司琼浓度。利用Excel软件计算累积溶出百分率及溶出参数,并进行比较分析。结果 3个厂家盐酸昂丹司琼片的体外溶出度均符合药典规定,但各自间存在一定差异。结论不同厂家盐酸昂丹司琼片的溶出情况存在一定差异。     

穴位指针法联合静脉滴注昂丹司琼治疗化疗所致恶心、呕吐的效果观察

目的：观察穴位指针法联合静脉滴注昂丹司琼治疗化疗所致恶心、呕吐的效果。方法将240例肿瘤化疗患者随机分成两组,治疗组采用穴位指针法联合静脉滴注昂丹司琼,对照组单纯静脉滴注昂丹司琼,观察两组预防、减轻恶心、呕吐的效果。结果治疗组的有效率明显高于对照组（P〈0.01）。结论穴位指针法联合静脉滴注昂丹司琼治疗化疗所致恶心、呕吐的效果优于单纯静脉滴注昂丹司琼。     

昂丹司琼口腔溶解薄膜剂含量测定方法的研究

目的建立昂丹司琼口腔溶解薄膜剂含量测定方法。方法采用HPLC法测定昂丹司琼口腔溶解薄膜剂中昂丹司琼的含量。结果 HPLC法测定的平均回收率为99.9%,RSD为0.3%,回收率良好。昂丹司琼在5.1¹022.4μg/mL浓度范围内浓度与峰面积呈良好的线性关系,r=1.0。结论采用HPLC法测定昂丹司琼口腔溶解薄膜中昂丹司琼的含量,专属性强,灵敏度高,重现性好,能够很好的控制产品的质量,将该法订入质量标准。     

基于FAERS数据库对5-羟色胺3受体拮抗剂不良事件的数据挖掘研究

目的 基于FAERS数据库挖掘研究目前国内外常用的5-羟色胺3受体拮抗剂（5-HT3RA）（昂丹司琼、格拉司琼、帕洛诺司琼、多拉司琼）的药品不良事件（ADE）信号,探索不良事件发生与药物的关系,为临床用药决策提供参考。方法 提取FAERS数据库2016年—2020年共20个季度的不良事件报告数据,采用报告比值比法（ROR）和综合标准法（MHRA）对四种5-HT3RA药物的报告进行信号挖掘,采用《国际医学用语词典》对不良反应用语进行标化统一,将筛选得到的不良事件信号进行分析和比较。结果 最终得到昂丹司琼不良事件信号991个,共涉及25个系统器官分类（SOC）,临床需特别关注的信号有各种先天性家族性遗传性疾病和妊娠过程中胎儿暴露。得到格拉司琼不良事件信号54个,共涉及10个SOC,临床需特别关注的信号有药物的使用问题、用药部位各种反应以及胃肠道反应。得到帕洛诺司琼不良事件信号1个,报告例数为5例,对应SOC为血液及淋巴系统疾病。结论 三种药物的ADE信号累及的主要系统器官有明显差异,其中昂丹司琼累及系统器官较多,妊娠期使用昂丹司琼可能具有致畸性。临床对肿瘤患者或其他人群使用5-HT3RA时...     

Intestinal obstruction in pregnancy by ondansetron

BackgroundOndansetron use for nausea and vomiting during pregnancy has increased in the last years, although its maternal and fetal safety is not conclusive.CaseWe describe a case of intestinal obstruction in a pregnant woman with severe nausea and vomiting of pregnancy treated with ondansetron, which is known to slow gut motility.ConclusionThe spontaneous reporting system of WHO confirms that this potentially life threatening complication is more common than what the peer review literature may suggest and needs to be looked into carefully, especially in view of the wide spread off-label use for NVP.     

Efficacy,safety and effectiveness of ondansetron compared to other serotonin-3 receptor antagonists (5-HT3RAs) used to control chemotherapy-induced nausea and vomiting: systematic review and meta-analysis

Introduction: Chemotherapy-induced nausea and vomiting are adverse effects responsible for worsening quality of life in cancer patients. To assess the efficacy, safety and effectiveness of serotonin receptor antagonist in cancer patients undergoing chemotherapy, comparing ondansetron with granisetron, dolasetron, tropisetron and palonosetron.

Areas covered: Systematic review and meta-analysis. The data were collected using CINAHL; CENTRAL; MEDLINE/PubMed; and LILACS databases; grey literature; and manual search. The methodological quality was assessed using the modified Jadad scale; Cochrane Collaboration’s tool for assessing risk of bias in randomized clinical trials and the Newcastle-Ottawa Scale for observational studies. The search was completed in November, 2015. 26 studies were included in the meta-analysis. Ondansetron exhibited similar efficacy than granisetron and tropisetron, as well as greater efficacy than dolasetron for acute vomiting. Palonosetron exhibited greater efficacy than ondansetron for delayed nausea and acute and delayed vomiting. The comparison of granisetron with ondansetron in the cohort studies showed no difference.

Expert commentary: In this review, palonosetron had increased efficiency compared with ondansetron, except in the subgroup analysis and acute nausea. Few cohort studies have been published addressing this topic.     

Formulation,evaluation and 32 full factorial design-based optimization of ondansetron hydrochloride incorporated taste masked microspheres

Abstract

Context: Masking the bitter taste of Ondansetron hydrochloride (ONS) may improve palatability, acceptance and compliance of ONS products.

Objective: ONS-loaded, taste-masked microspheres were prepared with a polycationic pH-sensitive polymer and 3² full factorial design (FFD) was applied to optimize microsphere batches.

Materials and methods: Solvent evaporation, in acetone--methanol/liquid paraffin system, was used to prepare taste-masked ONS microspheres. The effect of varying drug/polymer (D/P) ratios on microspheres characteristics were studied by 3² FFD. Desirability function was used to search the optimum formulation. Microspheres were evaluated by FTIR, XRD and DSC to examine interaction and effect of microencapsulation process. In vitro taste assessment approach based on bitterness threshold and drug release was used to assess bitterness scores.

Results: Prepared ONS microspheres were spherical and surface was wrinkled. ONS was molecularly dispersed in microspheres without any incompatibility with EE100. In hydrochloric acid buffer pH 1.2, ONS released completely from microsphere in just 10?min. Contrary to this, ONS release at initial 5?min from taste-masked microspheres was less than the bitterness threshold.

Conclusion: Full factorial design and in vitro taste assessment approach, coupled together, was successfully applied to develop and optimize batches of ONS incorporated taste-masked microspheres.     

阿托伐他汀联合氯吡格雷治疗短暂性脑缺血发作的临床研究

目的 对盐酸维拉佐酮的合成工艺进行改进。方法 以4-（4-乙酰基哌嗪-1-基）苯酚为起始原料,经Duff反应、取代、环化、脱保护、酰胺化得到关键中间体5-（1-哌嗪基）-苯并呋喃-2-甲酰胺,再与3-（4-氯丁酰基）-1H-吲哚-5-甲氰缩合、成盐得到盐酸维拉佐酮。结果 合成了目标化合物盐酸维拉佐酮,并利用¹H-NMR、MS确证了结构,质量分数为99.8%,该路线的总收率为22.5%。结论 该合成工艺原料廉价易得、操作简单,适于工业化生产。     

昂丹司琼对比托烷司琼预防上腹部分割放疗所致恶心呕吐的临床研究

目的 比较昂丹司琼和托烷司琼预防上腹部分割放疗所致恶心呕吐的有效性与安全性。方法 选择84例接受上腹部分割放疗的肿瘤患者为研究对象,采用随机数字表法分为昂丹司琼组（O组）和托烷司琼组（T组）,每组42例。记录两组患者放疗期间恶心呕吐及其他不良反应的发生情况。结果 O组急性期恶心的完全缓解（CR）率显著低于T组（81.0% vs. 57.1%, P=0.018）;两组延迟期和全期恶心的CR率（61.9% vs. 50.0%, P=0.272; 61.9% vs. 45.2%, P=0.126）比较,差异无统计学意义。两组急性期、延迟期及全期呕吐的CR率（71.4% vs. 64.3%, P=0.483; 59.5% vs. 57.1%, P=0.825; 66.7% vs. 57.1%, P=0.369）比较,差异均无统计学意义。两组头晕、头痛、疲乏、腹泻和便秘的发生率比较,差异均无统计学意义（P>0.05）。结论 昂丹司琼和托烷司琼预防上腹部分割放疗所致恶心呕吐具有相似的疗效和安全性,昂丹司琼预防急性恶心的效果优于托烷司琼。     

归芪益元膏提取工艺优化及质量控制方法研究

目的 优化归芪益元膏的提取工艺并建立其质量控制方法。方法 采用L₉(3⁴)正交试验法,以出膏率、总多糖含量及正丁醇浸出物含量的综合评价为指标,优化归芪益元膏提取工艺;采用薄层色谱(TLC)法,对煎膏剂中的黄芪、当归、枸杞子、人参进行定性鉴别;采用HPLC测定方中君药黄芪的主要活性成分毛蕊异黄酮葡萄糖苷的含量;参照中国药典2020年版检查其相对密度、不溶物和装量差异,建立其质量控制方法。结果 最佳工艺为加水量12倍,提取时间4 h,提取2次;TLC鉴定结果显示色谱图斑点清晰,分离度良好且专属性强;毛蕊异黄酮葡萄糖苷在0.089 6~1.344 0 µg内线性关系良好(r²=0.999 4),平均回收率为99.51%,RSD为2.59%(n=9);煎膏相对密度为1.39,不溶物和装量差异符合中国药典2020年版规定。结论 优选的水提工艺科学合理,质量标准有效可控,可用于归芪益元膏的质量控制。     

替诺福韦的合成工艺改进

目的：改进替诺福韦的合成工艺。方法：以亚磷酸二乙酯和多聚甲醛经缩合、酯化得到对甲苯磺酸羟甲基磷酸二乙基酯（4）。另以缩水甘油合成碳酸丙烯酯,与腺嘌呤反应得到9-（2-羟丙基）腺嘌呤（7）,在叔丁醇钠作用下与（4）经缩合、水解等反应制得抗病毒药物替诺福韦。结果：优化后的制备工艺成本低,操作简便,对环境污染减少。结论：新工艺的产率达到30％,适合工业生产。