载多烯紫杉醇聚乳酸-羟基乙酸微球的制备、表征及其药物稳定性

背景:目前临床使用的多烯紫杉醇注射液多采用吐温80作为增溶剂,容易导致过敏反应,且全身化疗不良反应大.采用聚乳酸-羟基乙酸包载多烯紫杉醇制备的缓释微球进行肿瘤间质化疗可提高肿瘤局部药物浓度,减轻全身不良反应.目的:制备一种用于肿瘤间质化疗的载多烯紫杉醇聚乳酸-羟基乙酸缓释微球,并考察其理化性质、体外释放及药物稳定性.方法:采用溶剂挥发法制备不同投料比载药微球,扫描电镜观察微球的表面形态、粒径,高效液相色谱法检测包封率、载药率及体外药物释放情况.将制备的微球于5,15,25 kGy 60Co 3种剂量辐照灭菌,体外细菌培养观察灭菌效果.结果与结论:制备的载药微球呈圆球形,表面光滑,分散良好,平均粒径为23.1 um.聚乳酸-羟基乙酸与多烯紫杉醇的投料比为100 mg,5 mg时可获得最佳的包封率(96 3%)和载药率(4.82%);载药微球体外4周平稳释放药物达81.6%,无明显突释效应,包裹在微球内的多烯紫杉醇结构稳定性明显提高;3种剂量60Co辐照后均未见短小芽孢杆菌生长.说明采用溶剂挥发法可制备粒径及分布适宜、释放周期较理想、药物稳定性好的载多烯紫杉醇聚乳酸-羟基乙酸缓释微球.     

复方中药聚乳酸微球兔膝骨性关节炎关节腔注入

背景:骨炎1号方由淫羊藿、补骨脂、当归三味中药组成,具有补肝益肾,强壮筋骨,活血化瘀,通络止痛的作用.目的:观察骨炎1号聚乳酸微球膝关节腔内注射干预骨性关节炎的可行性.方法:将新西兰大白兔以数字表法随机分成生理盐水组、玻璃酸钠组、骨炎1号聚乳酸微组.所有动物的右膝经手术制成骨性关节炎模型.造模后6周开始关节内干预注射生理盐水、玻璃酸钠、骨炎1号聚乳酸微球,1次/周,连续给药5次. 最后一次给药后2周在解剖显微镜下对患膝进行大体解剖学评分,并对关节软骨进行组织形态学观条.结果与结论:与生理盐水组相比,骨炎1号聚乳酸微球组和玻璃酸钠组均可降低实验动物的关节炎指数(P＜ 0.05)、减轻关节软骨的退变.骨炎1号聚乳酸微球组对关节的保护作用不及玻璃酸钠组,但两组间差异无显著性意义.说明骨炎1号聚乳酸微球制剂关节腔内注射干预骨性关节炎是可行的,对动物骨性关节炎具有一定的治疗作用.     

许旺细胞及小肠黏膜下层复合生长因子缓释微球修复周围神经缺损

背景：前期实验已初步证实许旺细胞复合小肠黏膜下层及碱性成纤维细胞生长因子构建的人工神经具有体外神经活性、趋化性。目的：观察许旺细胞及小肠黏膜下层复合碱性成纤维细胞生长因子缓释微球修复周围神经缺损后神经传导的再通情况。方法：制作SD大鼠坐骨神经缺损模型,随机分组：实验组以许旺细胞及小肠黏膜下层复合碱性成纤维细胞生长因子缓释微球修复,阳性对照组以许旺细胞及小肠黏膜下层复合游离碱性成纤维细胞生长因子修复,阴性对照组以许旺细胞及小肠黏膜下层修复,空白对照组以自体神经修复。结果与结论：术后16周实验组再生神经纤维数目,DiI示踪标记的阳性神经元数量、S-100及神经细丝蛋白的阳性表达率、髓鞘及再生轴突的超微结构恢复、神经传导速度及复合动作电位的改善均优于阳性对照组与阴性对照组（P〈0.05）。表明许旺细胞复合小肠黏膜下层及碱性成纤维细胞生长因子缓释微球构建的人工神经可重建坐骨神经缺损后的神经传导通路。     

许旺细胞及小肠黏膜下层复合生长因子缓释微球修复周围神经缺损

背景:前期实验已初步证实许旺细胞复合小肠黏膜下层及碱性成纤维细胞生长因子构建的人工神经具有体外神经活性、趋化性。目的:观察许旺细胞及小肠黏膜下层复合碱性成纤维细胞生长因子缓释微球修复周围神经缺损后神经传导的再通情况。方法:制作SD大鼠坐骨神经缺损模型,随机分组:实验组以许旺细胞及小肠黏膜下层复合碱性成纤维细胞生长因子缓释微球修复,阳性对照组以许旺细胞及小肠黏膜下层复合游离碱性成纤维细胞生长因子修复,阴性对照组以许旺细胞及小肠黏膜下层修复,空白对照组以自体神经修复。结果与结论:术后16周实验组再生神经纤维数目,DiI示踪标记的阳性神经元数量、S-100及神经细丝蛋白的阳性表达率、髓鞘及再生轴突的超微结构恢复、神经传导速度及复合动作电位的改善均优于阳性对照组与阴性对照组(P<0.05)。表明许旺细胞复合小肠黏膜下层及碱性成纤维细胞生长因子缓释微球构建的人工神经可重建坐骨神经缺损后的神经传导通路。     

注射用利培酮微球对依从性差的精神分裂症患者临床应用观察

近年来,随着非典型抗精神病药的临床应用,精神分裂症患者的疗效得到一定提高,但口服用药依从性仍然较差,有研究认为新型非典型抗精神病药坚持时间和传统抗精神病药并无显著差异［1］。不坚持治疗,依从性差是精神分裂症复发的主要原因［2］,因此使用疗效好而安全,依从性高的抗精神病药是治疗精神分裂症的关键。作者对44例治疗依从性差的精神分裂症患者采用注射用利培酮微球治疗,观察其治疗效果,现报告如下。     

肺部缓释微球治疗肺部疾病的性能及评价

背景：肺部因其特殊的生理结构而适合作为局部或全身用药的给药部位,而肺部缓释微球在肺部局部疾病治疗乃至全身疾病治疗方面的优越性尚缺乏更多的报道.目的：评价肺部缓释微球载体材料的释药性能以及临床给药途径的安全性,对比肺部缓释微球与其他肺部给药剂型的差异.方法：观察微球在肺部的分布及降解情况、肺组织的病理变化和连续给药对肺功能的影响.结果与结论：肺部缓释微球常用的材料有淀粉、聚乳酸等,具有生物可降解性、生物相容性和生物黏附性,并且缓释微球制备简单,对正常组织无损伤,安全性高,肺部缓释微球在体内有良好的肺靶向性,可提高药物的疗效,降低药物毒副作用,对肺组织无病理性损伤.     

氟比洛芬酯脂微球注射液对癌症疼痛及生存质量影响的临床观察

目的：观察氟比洛芬酯脂微球载体注射液治疗癌痛的疗效和副作用。方法：48例未使用阿片类药物的中重度癌性疼痛患者每天静脉注射50mg／5ml氟比洛芬酯脂微球载体注射液，分别就其疗效、生存质量改善情况及不良反应等方面进行评价。结果：氟比洛芬酯脂微球载体注射液治疗中、重度癌痛的有效率为71％，生存质量改善情况治疗前后比较差异有显著性意义（P〈0．05）。但未见一般非甾体类药物常见腹痛、消化道出血等副作用；也未见便秘、恶心、呕吐、嗜睡等阿片类药物常见不良反应。结论：氟比洛芬酯脂微球载体注射液治疗中重度癌痛疗效可靠，患者生存质量可得到改善，不良反应发生率较低，可部分作为临床候选药品或口服吗啡替代药。     

32P-玻璃微球瘤内注射抗肿瘤作用及对外周血白细胞的影响

目的观察32 P-玻璃微球(32 P-GMS)的抑瘤效果及对外周血白细胞的影响。方法称重法检测32 P-GMS对小鼠S180肉瘤的抑瘤率及对外周血白细胞计数和淋巴细胞分类的影响。结果 32P-GMS瘤内注射的抑瘤率分别为15.2%、20.4%、32.5%;治疗组小鼠随32P-GMS剂量的增大,白细胞呈明显的上升趋势;各治疗组淋巴细胞分类百分率高于对照组,剂量超过0.74MBq/mL有开始下降的趋势。结论 32 P-GMS瘤内注射有很强的抗肿瘤作用,但对外周血白细胞计数和淋巴细胞分类有明显影响。     

乳酸-羟基乙酸共聚物缓控释微球的制备及突释成因与影响因素

背景:乳酸-羟基乙酸共聚物是一种生物可降解高分子材料,以乳酸-羟基乙酸共聚物为原料制备的载药微球和纳米粒既可提高药物的稳定性,又能实现缓释、控释和靶向释放.目的:分析乳酸-羟基乙酸共聚物缓控释微球的制备方法以及突释的成因、影响因素和改进方法.方法:应用计算机检索1990/2010中国期刊全文数据库和PubMed数据库与乳酸-羟基乙酸共聚物缓控释微球的制备及突释联系紧密的文章.结果与结论:目前乳酸-羟基乙酸共聚物缓释微球制备方法主要有单凝聚法、乳化-固化法、喷雾干燥法.造成其突释的原因首先是药物分子和聚合物分子之间的相互作用太弱,导致药物很容易从微球进入释放递质中,其次是在微球释放初期,药物从微球中的孔洞和缝隙中释放出来导致突释.影响突释程度的具体因素有乳酸-羟基乙酸共聚物的相对分子质量、浓度、微球载药量、主药理化性质、微球制备方法及制备参数等.虽然国内外对突释机制以及控制突释措施的研究都还处于初步阶段,通过对各影响因素加以适当优化与控制,可在一定程度上减少微球的突释率,突释问题应该能够得到解决和控制.     

乳酸-羟基乙酸共聚物缓控释微球的制备及突释成因与影响因素

背景：乳酸-羟基乙酸共聚物是一种生物可降解高分子材料,以乳酸-羟基乙酸共聚物为原料制备的载药微球和纳米粒既可提高药物的稳定性,又能实现缓释、控释和靶向释放。目的：分析乳酸-羟基乙酸共聚物缓控释微球的制备方法以及突释的成因、影响因素和改进方法。方法：应用计算机检索1990/2010中国期刊全文数据库和PubMed数据库与乳酸-羟基乙酸共聚物缓控释微球的制备及突释联系紧密的文章。结果与结论：目前乳酸-羟基乙酸共聚物缓释微球制备方法主要有单凝聚法、乳化-固化法、喷雾干燥法。造成其突释的原因首先是药物分子和聚合物分子之间的相互作用太弱,导致药物很容易从微球进入释放递质中,其次是在微球释放初期,药物从微球中的孔洞和缝隙中释放出来导致突释。影响突释程度的具体因素有乳酸-羟基乙酸共聚物的相对分子质量、浓度、微球载药量、主药理化性质、微球制备方法及制备参数等。虽然国内外对突释机制以及控制突释措施的研究都还处于初步阶段,通过对各影响因素加以适当优化与控制,可在一定程度上减少微球的突释率,突释问题应该能够得到解决和控制。     

A multi-center evaluation of the McGill Pain Questionnaire: results from more than 1700 chronic pain patients.

We argue that the conflicting results reported in previous studies examining the factor structure of the McGill Pain Questionnaire Pain Rating Index (PRI) can be explained by differences in the patient samples and statistical analyses used across studies. In an effort to clarify the factor structure of the PRI, 3 different factor models were compared using confirmatory factor analysis in 2 samples of low-back pain patients (N = 1372) and in a third sample of patients suffering from other chronic pain problems (N = 423). A 4-factor model, similar to those obtained in previous studies where multiple criteria were used to determine the number of factors extracted, best explained covariation among PRI subclasses. However, relatively high interfactor correlations (approximately two-thirds of the variance explained by the best fitting factor structure was common variance) cast doubt on the discriminant validity of PRI subscales; examination of relationships between the PRI and MMPI subscales also failed to provide evidence of the discriminant validity or clinical utility of PRI subscales. Reducing the information from the 10 PRI sensory subclasses to a single subscale score may seriously limit the usefulness of the PRI. Alternate methods of using PRI data are suggested.     

Effect on pain intensity of injection sites and speed of injection associated with intramuscular penicillin

The aim of this one‐group, quasi‐experimental study was to examine the effect of choice of injection site and injection duration on the intensity of pain associated with intramuscular penicillin injection. Injections containing the same dose of drug were administered 12 hours apart for each patient over 5 s/mL and 10 s/mL durations in the dorsogluteal and ventrogluteal sites. Sixty patients who had a medical order for intramuscular penicillin at least twice in a day and for two successive days at the same dose were included in the study. No difference in pain was perceived by participants between the two injection durations at either the dorsogluteal or the ventrogluteal site. This study showed that intramuscular penicillin can be administered to either site over 5 s/mL or 10 s/mL durations. There is a need for further research with a randomized controlled design in different settings and in a larger sample on the impact of choice of injection site and injection duration on pain intensity.     

Exercise and quality of life in patients with cystic fibrosis: A 12-week intervention study

It was hypothesised that increased exercise capacity is related to improved quality of life (QoL) in patients with cystic fibrosis (CF). A 12-week individually tailored unsupervised aerobic exercise programme was offered to 42 patients with CF. At the start and at the end of the exercise programme, data on QoL, current exercise habits and preferences, anthropometric data, exercise test, and lung function test were collected. Adherence was observed by a heart rate (HR) monitor. A total of 24 patients accepted to be enrolled in the exercise programme and 14 completed the programme. Another 14 patients declined to be enrolled in the exercise programme but completed the Cystic Fibrosis Questionnaire for Adolescents and Adults (CFQ-R 14+). Four patients did not want to participate at all. The 14 patients completing the exercise programme had a significantly increased VO_2max, but they showed no significant change in total QoL score. However, the scores in the domain of treatment burden and emotional functioning increased significantly. There was no significant difference in QoL and lung function between patients participating in the exercise programme (n?=?24) and non-participants (n?=?14). A 12-week individually tailored unsupervised aerobic exercise programme where HR monitors were used significantly affected VO_2max. Improvement in QoL could not be demonstrated in this study.     

Exercise and quality of life in patients with cystic fibrosis: A 12-week intervention study

It was hypothesised that increased exercise capacity is related to improved quality of life (QoL) in patients with cystic fibrosis (CF). A 12-week individually tailored unsupervised aerobic exercise programme was offered to 42 patients with CF. At the start and at the end of the exercise programme, data on QoL, current exercise habits and preferences, anthropometric data, exercise test, and lung function test were collected. Adherence was observed by a heart rate (HR) monitor. A total of 24 patients accepted to be enrolled in the exercise programme and 14 completed the programme. Another 14 patients declined to be enrolled in the exercise programme but completed the Cystic Fibrosis Questionnaire for Adolescents and Adults (CFQ-R 14+). Four patients did not want to participate at all. The 14 patients completing the exercise programme had a significantly increased VO(2max), but they showed no significant change in total QoL score. However, the scores in the domain of treatment burden and emotional functioning increased significantly. There was no significant difference in QoL and lung function between patients participating in the exercise programme (n?=?24) and non-participants (n?=?14). A 12-week individually tailored unsupervised aerobic exercise programme where HR monitors were used significantly affected VO(2max). Improvement in QoL could not be demonstrated in this study.     

A multi-center evaluation of a new immunoenzymometric assay for human choriogonadotropin

A new, rapid, monoclonal immunoenzymometric assay for human choriogonadotropin (HCG), the Enzymun-Test HCG (Boehringer Mannheim GmbH), was evaluated by 15 laboratories in 10 European countries. Inter-assay percent CVs ranged from 5.4 to 40.5, 2.4 to 15.4, and 2.3 to 17.1 for low, medium, and high dose sera, respectively. Mean assay sensitivity was 0.34 mIU/mL HCG. Analytical recovery in serum ranged from 75 to 119%. Serial dilutions of HCG in normal human serum and in assay zero standard were found to be linear. Cross-reactivity with lutropin, follitropin, and thyrotropin was negligible. Serum reference values were established for normals and all stages of pregnancy. Comparative studies with nine other HCG immunoassays were carried out using a range of normal, pregnancy, and tumour sera. We conclude that this is an acceptable assay for monitoring HCG-producing tumours and pregnancy.     

Patient-controlled oral analgesia at acute abdominal pain: A before-and-after intervention study of pain management during hospital stay

AimTo investigate the patient experience of pain management, when patient-controlled oral analgesia was compared with standard care for patients admitted to hospital with acute abdominal pain. The primary outcome measures were pain intensity and patient perception of care.BackgroundPain management of patients admitted to hospital with acute abdominal pain can be insufficient. Patient involvement in health care has been seen to have benefits for patients.MethodsA before-and-after intervention study was conducted in an emergency department observation unit and a surgical department. Data were collected from a questionnaire (APS-POQ-R-D) with the six subscales: pain severity, perception of care, interference with activity, interference with emotions, side effects and patient-related barriers.ResultsA total of 156 patients were included. During admission the median score (0–10 scale) for the pain intensity and patient perception of care subscale was 4 (p = 0.96) and 8 (p = 0.92), respectively, in both the control and intervention group. On the activity subscale, the median scores were 6 and 5 (p = 0.17); on the emotion subscale, the scores were 5 and 4 (p = 0.31); and on the side effect subscale, the scores were 3 and 4 (p = 0.18) in the control and intervention group, respectively. Overall, the score was 5–8 at one item about being allowed to participate in decisions about pain treatment as much as wanted.ConclusionPatient-controlled oral analgesia did not improve patient experience of pain management for patients admitted to hospital with acute abdominal pain.     

Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee

The efficacy and safety of a once-daily extended-release formulation of tramadol hydrochloride (tramadol ER) was evaluated in patients with moderate to severe chronic pain of osteoarthritis (OA). This was a randomized, double-blind, placebo-controlled, parallel-group, 12-week study. Eligible patients with radiographically confirmed OA of the knee meeting the American College of Rheumatology diagnostic criteria, defined by knee pain and presence of osteophytes, plus at least age >50 years, morning stiffness <30 minutes in duration, and/or crepitus, entered a 2-7 day washout period during which all analgesics were discontinued. When pain at the index knee joint reached > or =40 mm (0-100 mm VAS), patients were randomized to tramadol ER or placebo. Tramadol ER was initiated at 100 mg QD and increased to 200 mg QD by the end of 1 week of treatment. After the first week, further increases to tramadol ER 300 mg or 400 mg QD were allowed. Outcome measures included Arthritis Pain Intensity Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Scale (WOMAC) Pain, Stiffness, Physical Function VAS subscales, Patient and Physician Global Assessment of Therapy, Sleep, dropouts due to insufficient therapeutic effect, and adverse events. Two hundred forty-six patients were randomized (tramadol ER 124, placebo 122). There were no baseline differences between the two treatments. The mean age was 61 years, mean duration of OA 12.9 years, and the mean tramadol ER dose was 276 mg QD. All efficacy outcome measures favored tramadol ER over placebo. On the primary outcome variable of average change from baseline in Arthritis Pain Intensity VAS over 12 weeks, tramadol ER was superior to placebo (least squares mean change from baseline: 30.4 mm vs. 17.7 mm, P < 0.001). Significant differences from placebo were evident at week 1, the first post-treatment visit. Similarly, outcomes on the WOMAC Pain, Stiffness and Physical Function subscales, the WOMAC Composite Scale, dropouts due to insufficient therapeutic effect, Patient and Physician Global Assessment of Therapy, and Sleep were all significantly better with tramadol ER than placebo (P < 0.001 to < 0.05). Treatment with tramadol ER results in statistically significant and clinically important and sustained improvements in pain, stiffness, physical function, global status, and sleep in patients with chronic pain. A once-a-day formulation of tramadol has the potential to provide patients increased control over the management of their pain, fewer interruptions in sleep and improved compliance.