紫杉醇靶向制剂的研究进展

目的介绍紫杉醇靶向制剂的研究进展。方法综述近年来国内外相关研究,介绍紫杉醇靶向制剂的制备方法、性能和药效等,指出目前紫杉醇靶向制剂的研究前景。结果紫杉醇靶向制剂不仅提高紫杉醇的溶解度,而且降低其毒副作用。结论紫杉醇靶向制剂为癌症化疗提供了新的研究途径,是很有临床应用前景的抗癌药物剂型。     

紫杉醇靶向制剂的研究进展

目的:介绍紫杉醇靶向制剂的研究进展。方法:综述近年来有关的国内外文献,介绍和评价紫杉醇靶向制剂的制备、性质和药效等。结果:紫杉醇靶向制剂可以大大提高药物疗效,降低毒副作用。结论:紫杉醇靶向制剂为癌症化疗开辟了新的途径,可望在不久的将来,应用于临床     

抗HER2/neu受体拟肽修饰的紫杉醇白蛋白纳米粒的血液毒性和病理学毒性研究（英文）

纳米制剂具备高载药量、靶向性积聚以及表面修饰性质,被广泛应用于临床诊断和治疗,但是相关的毒性研究很少。为了研究白蛋白纳米制剂静脉注射后对正常组织的毒性,我们先通过高压均质法制备稳定、均一的紫杉醇白蛋白纳米粒,通过共价键将靶向肿瘤细胞HER2/neu受体的拟肽AHNP结合于纳米粒表面得到靶向修饰的纳米粒,并考察其理化性质。建立HER2受体过表达的荷瘤裸小鼠模型,静脉注射纳米制剂和紫杉醇传统注射液后取血进行血常规比较分析,发现紫杉醇白蛋白纳米粒和AHNP靶向修饰的紫杉醇白蛋白纳米粒均避免了传统注射液引起的粒细胞减少症和贫血作用。对动物肿瘤和重要组织进行病理切片、H&E染色分析,发现AHNP靶向修饰显著提高紫杉醇白蛋白纳米粒的抗肿瘤效果。紫杉醇白蛋白纳米粒和紫杉醇溶液均引起严重的肝损伤,AHNP靶向修饰能显著降低纳米粒对于肝脏的损伤,但可能增加个别动物的肺部损伤。     

人血浆蛋白多烯紫杉醇纳米粒子的自组装及对肿瘤的靶向性

目的：提高多烯紫杉醇的溶解度,提高其靶向性能。方法用二硫键断裂法制备人血清白蛋白多烯紫杉醇纳米粒子,并用电镜进行观察。对粒子载药量、稳定性及粒子对肿瘤部位趋向性进行表征。结果二硫键断裂法成功组装了白蛋白?多烯紫杉醇纳米粒子。电镜观察该纳米粒子外貌为80～100 nm左右的球形粒子,高效液相和蛋白质定量检测多烯紫杉醇载药量可达21．5％。结果白蛋白多烯紫杉醇纳米制剂可显著提高多烯紫杉醇的溶解度,提高对肿瘤靶向性。结论白蛋白?多烯紫杉醇纳米粒子对肿瘤细胞具有良好的靶向作用,具有临床运用的潜在价值。     

白蛋白结合型紫杉醇的临床研究进展

白蛋白结合型紫杉醇(NAB-P)为紫杉醇的特殊靶向制剂,其疗效好且不良反应较少。本文主要综述其近两年国内外的临床研究进展。     

磁性靶向紫杉醇微球制备的初步研究

目的：制备磁性靶向紫杉醇微球.方法：以紫杉醇和纳米Fe3O4为材料制备出磁性靶向紫杉醇微球,并利用高分辨透射电子显微镜（HRTEM）观察微球的形貌,同时采用紫外可见分光光度法测定微球的载药量和包封率.结果：磁性靶向紫杉醇微球的载药量为3.013%,包封率为35.26%.结论：通过实验研究制备了磁性紫杉醇微球,具有靶向定位功能,形成一种磁靶向给药系统.     

天然抗癌药物紫杉醇制剂的探究

通过查阅资料并进行分析,综述了近5年来紫杉醇的新剂型如脂质体、纳米粒、凝胶、植入剂和药物释放支架等,并对其可行性进行了分析.当前紫杉醇的新剂型研究主要围绕去除或减少原制剂中的表面活性剂以及制备水溶性良好的紫杉醇前药等工作来开展,以期提高药物的水溶性、降低药物的不良作用.从中推知紫杉醇未来制剂的研发重点将集中在紫杉醇局部或靶向缓控释制剂,紫杉醇口服给药也将获得突破.     

肺靶向多西紫杉醇壳聚糖微球的制备与工艺优化

目的：研制肺靶向多西紫杉醇壳聚糖微球,并对处方工艺进行筛选。方法：以壳聚糖为载体,采用乳化-化学交联法制备多西紫杉醇壳聚糖微球。在单因素考察的基础上,利用正交试验设计优化微球制备工艺,采用HPLC法测定微球的载药量与包封产率。结果：制得的微球显微观察形态圆整、表面光滑,无粘连;平均粒径为（8．63±0．27）μm,粒径7—12μm的微球平均占总数的83．5％,载药量为（25．01±1．80）％,包封产率为（85．54±2．21）％。结论：筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求;该制剂有可能成为临床肺部肿瘤治疗的一种靶向制剂。     

紫杉醇纳米级给药系统研究概述

目的：介绍近年来国内紫杉醇纳米级给药系统的研究进展。方法：查阅近几年国内相关文献并进行整理分析。结果：紫杉醇纳米级给药系统具有控释性、靶向性等优点,并显现出较好的抗动物癌模型效果。结论：紫杉醇纳米级给药系统为癌症的有效治疗带来新的突破。     

紫杉醇磁性脂质体的制备与抗肿瘤作用研究

目的制备紫杉醇磁性纳米脂质体,并研究其对3种肿瘤细胞的抑制效果。方法应用超声薄膜分散法制备紫杉醇磁性纳米脂质体,通过正交设计来优化制备工艺,噻唑蓝（MTT）法研究其对肿瘤细胞的抑制效果。结果最佳处方和工艺条件为：磷脂酰胆碱：胆固醇为4：1,紫杉醇：（磷脂酰胆碱+胆固醇）为1：30,超声处理时间30 min,磁粉：紫杉醇为1：1,聚山梨酯 80：紫杉醇为4：1,聚乙二醇1 000：紫杉醇为8：1;制备的紫杉醇磁性纳米脂质体包封率约85.8%,平均粒径约150 nm;对3种肿瘤细胞均有良好的抑制效果,并呈现一定的缓释作用。结论该方法制备的紫杉醇磁性纳米脂质体包封率较高,分布均匀,对3种肿瘤细胞抑制效果较好,符合靶向制剂的要求。     

Dapsone-associated fixed drug eruption

Introduction: Dapsone is a sulfone drug used to treat infectious conditions and also numerous dermatologic diseases. Fixed drug eruption is a distinctive adverse cutaneous reaction associated with the initial administration and subsequent delivery of a specific agent.

Areas covered: The authors preformed a literature search using the following keywords: dapsone, fixed drug eruption, and adverse cutaneous drug reaction. Bibliographies were also reviewed for pertinent articles. The results were combed for relevant papers and reviewed. Articles pertaining to dapsone-associated fixed drug eruption were included.

Expert commentary: The majority of cases of dapsone-associated fixed drug eruption in the literature come from Africa or India where there is a high prevalence of patients treated for leprosy. Characteristics of these cases are similar to fixed drug eruption described in the western literature, with differences in frequency of multiple versus solitary lesions. Dapsone-associated fixed drug eruption should be considered when reviewing the drug history of a patient with fixed drug eruption. In the case of darker pigmented individuals, multiple fixed drug eruption lesions may be more common. Multiple lesions may mimic Kaposi’s sarcoma in human immunodeficiency virus positive patients. Dapsone-associated fixed drug eruption should be considered in the differential diagnosis of multiple hyperpigmented lesions.     

Polypharmacy in a general surgical unit and consequences of drug withdrawal

AIMS: To identify drug usage/withdrawal in surgical patients and the relative risk this imposes on postoperative surgical complications. METHODS: A prospective survey of patients' medicines, oral intake (food/fluids/ medicines) and postoperative complications was carried out in the General Surgical Unit, Dunedin Hospital, Dunedin, New Zealand. RESULTS: One thousand and twenty-five general surgical patients aged >/= 16 years, were entered into the study. Half of the patients were taking medicines unrelated to surgery. On average these patients received 9 different drugs (range 1-47) from a selection of 251, of which 21% were released in the last 10 years. The mean number of these drugs taken increased with age, vascular surgery and other major procedures. The majority of patients (53%) were taking drugs for cardiovascular problems. Only 8% of admissions were on the drugs more traditionally recognized to be of importance to the surgery, i.e. steroids and diabetic therapy. With respect to risk, taking a drug unrelated to surgery was associated with an increased relative risk of a postoperative complication by 2.7 (95% C.I. 1.76-4.04) compared with those who were not taking any drug. Cardiovascular drugs contributed significantly to this risk; when they were excluded from analysis, the risk dropped to 1.8 (95% C.I. 1.14-2.93). Death may be more common in those taking ACE inhibitors. Drug withdrawal and complications were analysed and as the time without medicines increased (range 1-42 days) so did the complication rate (chi2 = 14.7, DF = 2, P = 0.007). Of those patients who were taking a cardiovascular medicine and were without their normal medicines for a period of time postoperatively, 12% suffered a cardiac complication. CONCLUSIONS: Many patients admitted to a general surgical ward, are taking medicines unrelated to surgery. Drug therapy unrelated to surgery is a useful predictor for increased postoperative complications and one for which preventive action can be taken. This study provides evidence that withdrawal of regular medicines may add significant risk to the surgery and further complicate outcome. The longer patients were without their regular medicines the more nonsurgical complications they suffered. Reintroduction of patients' regular medicines early in their postoperative course may decrease morbidity and mortality in-patients.     

Challenges in adopting evidence-based school drug education programmes

ISSUES: The paper discusses the school-based challenges that may moderate the implementation of evidence-based drug education in schools. APPROACH: Knowledge about what constitutes an effective evidence-based drug education programme is discussed in relation to the challenge of delivery in the school setting. Research demonstrates that drug education should be engaging, incorporate interactive learning strategies, stimulate higher-order thinking, promote learning and be transferable to real life circumstances. This may difficult to accomplish in practice, as a range of contextual challenges and ideological assumptions may moderate the teacher's capacity to deliver a programme of this nature. KEY FINDINGS: Collaborative learning strategies are not the norm in schools and therefore teachers may find interactive drug education programmes difficult to adopt. Conflicting ideological assumptions about effective epistemological approaches to drug education may also direct the way in which teachers modify programmes in the local context. IMPLICATIONS: Teachers need professional training and support if they are to adopt successfully evidence-based school drug education programmes. This support may be enhanced if it includes whole school approaches to effective pedagogy and the development of pro-social classroom environments. CONCLUSION: Drug education research should take account of the complexities of implementation in the school setting and investigate further the professional and organisational support that teachers require in order to maintain high-quality provision in the school context.     

老年住院患者口服药使用情况调查

目的：了解某医院老年住院患者口服药使用情况，并调查不良药物相互作用发生情况。方法：随机抽取2002年9月2日、9月11日及9月27日住院者中＞60岁老年患者摆药单452份，统计患者的基本情况及口服药应用种类，使用《合理用药软件系统》2002版检查每份摆药单中存在的药物相互作用。结果：超过40％的老年患者口服6种以上的药物；117份病例存在中度的不良药物相互作用，26份存在严重的相互作用。结论：该院老年住院患者口服药使用种类过多，产生不良药物相互作用情况较多，部分病例中存在可能危及生命的药物联合应用。     

齐鲁儿童医院14例醒脑静注射液静脉滴注致药品不良反应分析

目的：探讨醒脑静注射液药物不良反应发生的特点及规律,指导临床合理用药。方法：收集山东大学齐鲁儿童医院2016年醒脑静注射液所致14例不良反应报告,对患儿年龄、用药原因、用法用量、使用溶媒、不良反应累及器官及不良反应严重程度等进行整理和统计,分析发生不良反应的原因和规律。结果：醒脑静注射液本身可能引起过敏反应;其所引起的不良反应病例中1~3岁儿童占57.14%;非说明书适应证用药患儿占80%;以5%葡萄糖为溶媒所致的ADR达78.57%;儿童使用醒脑静注射液发生严重不良反应达71.43%。结论：醒脑静注射液使用过程中应明确其功能主治,禁止超功能主治用药;使用0.9%氯化钠注射液作为溶媒更安全;减少超药品说明书用药;3岁以下患儿在有替代药物的情况下,不使用醒脑静注射液;生产厂家应加强醒脑静注射液用于儿童的安全性研究。     

Drug Solubilization Behavior During in Vitro Digestion of Suspension Formulations of Poorly Water-Soluble Drugs in Triglyceride Lipids

PURPOSE: The purpose of this study was to characterize the solubilization and precipitation characteristics of a range of poorly water-soluble drugs during the in vitro digestion of long-chain or medium-chain triglyceride (TG) lipid suspension formulations. METHODS: TG suspensions of model drugs (present at double their equilibrium solubilities in the respective lipid) were digested in vitro and the drug solubilization and precipitation pattern in the resulting digests analyzed. RESULTS: For griseofulvin, diazepam, and danazol, solubilization of the small mass of drug originally presented in the TG lipid was efficient with only a small proportion of the dose precipitating and being recovered in the pellet phase after digestion of the TG lipid. For the more lipophilic and lipid-soluble drugs (cinnarizine, halofantrine), in which higher drug loadings were possible, significant enhancement in drug solubilization in the postdigestion aqueous phase was not apparent compared with simple TG lipid solutions. CONCLUSIONS: Suspensions of drugs, which are poorly soluble in water and TG lipid, may prove beneficial as the relatively high solubilizing capacity of the colloidal phases produced on TG digestion will likely exceed the mass of drug that could have been administered as a simple lipid solution. However, for more lipid-soluble drugs, suspension formulations may offer little benefit as sufficiently high drug loadings can otherwise be achieved with simple solution formulations that still provide for adequate solubilization after TG digestion.     

Comparative assessment of four drug interaction compendia

AIMS: To assess the consistency of inclusion and grading of major drug interactions for 50 drugs in four leading international drug interaction compendia. METHODS Four international drug interaction compendia were compared: the drug interactions appendix of the British National Formulary, the interaction supplement in the French drug compendium Vidal, and two US drug interaction compendia, Drug Interaction Facts and the Micromedex (Drug-Reax) program. Major interactions were defined as potentially hazardous in BNF or with the warning 'contraindication' or 'avoid' in Vidal or with the significance grading 1 or 2 in DIF. Major interactions for a list of 50 drugs were searched in all four compendia. RESULTS: A total of 1264 interactions meeting the inclusion criteria were identified for these 50 drugs. After deletion of 169 duplicates, 1095 interactions were included in the analysis. Of the drug interactions classified as major in any one compendium between 14% and 44% were not listed in the other compendia. The grading systems used for the severity and the quality of the supporting evidence in Micromedex and DIF were inconsistent. CONCLUSIONS: There is a lack of consistency in the inclusion and grading of drug interactions of major significance for 50 drugs across the four drug compendia examined. This may reflect the lack of standardization of the terminology used to classify drug interactions and the lack of good epidemiological evidence on which to base the assessment of the clinical relevance of drug interactions.     

干扰素不良反应文献分析

目的:探讨干扰素临床应用时发生不良反应的特点及一般规律,为临床合理用药提供参考。方法:对2000~2006年国内医药学术期刊报道的64例干扰素致不良反应病例进行统计、分析。结果:干扰素所致不良反应在30~39a年龄段发生比例较高(占35.94%),在性别分布上男性(占68.75%)所占比例高于女性(占31.25%)。不良反应多在多次给药后发生,其临床表现以免疫系统的变态反应最常见,可累及多个器官或系统。结论:临床使用干扰素时应根据用药指征合理用药,加强用药监测,以预防和减少不良反应的发生。     

我院106例不合理应用抗菌药物致不良反应回顾性分析

目的:减少人为因素造成的ADR。方法:采用回顾性分析方法,调查2005~2006年山东淄博市中心医院收集的ADR报告,并按照《抗菌药物临床应用指导原则》统计、分析不合理应用抗菌药物致ADR情况。结果:全院收集的ADR报告表共1 036份,其中抗菌药物引起432例(占41.7%)。按照抗菌药物合理应用标准进行评价分析,最终确定106例属于不合理用药所致,占抗菌药物引起ADR的24.54%。结论:抗菌药物的不合理应用可使ADR发生率升高。