广东省医疗机构化学药制剂注册申报存在的问题及建议

目的:为保障临床用药安全和促进医疗机构特色化学药制剂发展提供参考。方法:从新制剂注册申报、补充申请申报、再注册申报这3个方面对广东省医疗机构化学药制剂注册申报技术审评过程中发现的问题进行归纳,分析引发上述问题的原因并给出相关建议。结果与结论:医疗机构化学药新制剂注册申报存在立题依据不充分、配制工艺研究缺少关键工艺参数、稳定性考察试验条件不符合药典要求等问题;补充申请申报存在处方组成不合理、内包材与药物发生相互作用、贮藏条件设定不合理等问题;再注册申报存在市场上已有药品供应、申报单位不具备生产条件、原辅料无法购买、注意项不完整等问题。造成这些问题的主要原因是化学药制剂研究技术指导原则缺失、《医疗机构制剂配制质量管理规范》不完善、《医疗机构制剂注册管理办法》不允许化学药制剂委托配制及部分化学药制剂品种已经不能适应新形势的发展等。完善医疗机构制剂相关法规和以安全有效为标准选择性发展医疗机构化学药制剂品种是解决思路。今后可从制定医疗机构化学药制剂研究技术指导原则、细化成品留样的规定、增加持续稳定性考察的规定、允许已有批准文号化学药制剂委托配制、淘汰不适应新形势发展的医疗机构化学药制剂品种并发展有价值的医疗机构化学药制剂品种等方面入手,为临床提供更多安全、有效的化学药制剂。     

云南省医疗机构制剂注册申报现状浅析

目的:为医疗机构制剂新品种注册申报提供参考。方法:对2005年至2011年云南省医疗机构制剂申报情况及注册审评工作现状进行分析,总结申报资料中普遍存在的问题。结果与结论:目前医院制剂申报中普遍存在基础性试验资料不规范如处方及工艺研究不足,制剂质量控制存在隐患,不重视稳定性试验考察,缺乏药效学研究、毒性和安全性评价等情况。建议申报人通过加强科研协作、并按相关技术指导原则进行新品种注册申报工作。     

2012年北京市医疗机构制剂注册申请概况及申报中应关注的若干问题

目的总结并分析2012年北京市医疗机构制剂注册申请概况及申报中应关注的若干问题,旨在提出一些制剂申报过程中应关注的事项,以供制剂注册申请人参考。方法通过对2012年北京市医疗机构制剂的申报情况进行汇总,同时与往年的数据进行比较和分析,针对北京市医疗机构制剂注册申请及申报具体过程中遇到的实际问题,提出制剂申请过程中的注意事项。结果通过对近几年申报的医疗机构制剂注册申请及申报的汇总及分析,发现存在一些不符合国家食品药品监督管理局《医疗机构制剂注册管理办法》(试行)和北京市药品监督管理局制定的《北京市医疗机构制剂注册管理办法实施细则》(试行)中要求的共性问题,需要提请申请人予以关注,以免影响申报进程。这些共性问题主要包括以下几方面:医疗机构化学药品制剂原料药的要求、中药饮片入药检验的要求、中药制剂功能主治书写应规范、制剂规范和包装规格的要求、延长有效期的补充申请的要求和关于医疗机构制剂价格的管理规定等。结论医疗机构制剂是指医疗机构根据本单位的临床需要并经有关部门批准而配制、自用的固定处方制剂,因其应是市场上没有供应的制剂品种,因此该种制剂注册申请及申报中遇到的问题更应该引起申报单位或个人的注意,以免影响其正常注册及申报。     

对医疗机构制剂再注册工作中相关问题的认识和探讨

目的:为医疗机构制剂再注册及管理工作提供参考。方法:分析2010年北京市医疗机构制剂品种再注册和标准整顿工作中存在的相关问题并提出建议。结果与结论:医疗机构制剂存在制剂品种繁杂、质量标准陈旧、处方和工艺不规范等亟待解决的问题。建议优化制剂品种结构并进一步完善质量标准等;应充分发挥制剂再注册工作的作用,规范与创新管理,保证制剂质量与安全。     

广东省医疗机构中药制剂注册申报存在问题及对策

目的：分析广东省医疗机构中药制剂注册申报存在的问题，为促进医疗机构中药制剂的研发与发展提供参考。方法：通过对2016-2018年60份广东省医疗机构中药制剂注册申报资料进行梳理、归纳，从技术角度阐述医疗机构中药制剂注册申报资料存在的不足。结果与结论：经过技术审评，符合《医疗机构制剂注册管理办法》（试行）有关规定的申报资料24份，通过率为40%。对未通过技术审评的36份注册申报资料的各项目进行系统分析发现，自《医疗机构制剂注册管理办法》实施以来，医疗机构中药制剂研发水平虽有较大程度的提高，但在协定处方使用历史、配制工艺研究、药用辅料使用、直接接触制剂的包装材料和容器选择、申报资料完整性等方面仍存在诸多问题，有较大的提升空间。建议医疗机构引入制剂质量源于设计（quality-by-design，QbD）的研发理念，加大对医疗机构制剂的重视程度；医疗机构制剂注册配套的法规要及时出台，以促进其逐步完善。     

对《医疗机构制剂注册管理办法(试行)》有关问题的探讨

目的:为完善医疗机构制剂注册法规、促进医疗机构制剂发展提供参考。方法:通过对《医疗机构制剂注册管理办法(试行)》内容进行梳理、总结和归纳,针对其在医疗机构制剂定义等方面存在的不足,提出相应的完善建议。结果与结论:《医疗机构制剂注册管理办法(试行)》自2005年颁布至今已12年,存在医疗机构制剂定义范畴过宽、注册申报资料要求不甚严谨、临床研究规定模糊不清、临床应用再评价工作不足、不予批准情形缺失等方面的不足。针对上述不足,笔者提出缩小医院制剂定义范畴、修改注册申报资料要求、明确临床研究规定、增加新制剂监测期及增订不予批准的情形等建议,从而完善医疗机构制剂注册法规、促进我国医疗机构制剂发展。     

规范制剂申报程序 加强制剂监督管理——解读《医疗机构制剂注册管理办法》

国家食品药品监督管理局于2005年6月颁布了《医疗机构制剂注册管理办法》(试行),2005年8月1日起施行,这对规范我国医疗机构制剂的申报与审批具有重要意义。《办法》共六章四十七条,四个附件,分别就制剂申报审批、调剂使用、补充申请与再注册、监督管理等作了详细规定,附件中明确了制剂注册、调剂使用、再注册的申报资料的项目和要求。为便于正确理解和执行该办法,现结合北京市制剂注册工作的实际情况,将其主要内容与要求介绍如下。制剂及其研制的基本要求制剂定义医疗机构制剂是指医疗机构根据本单位临床需要、经批准而配制、自用的固定处方…     

率先开展网上无纸化电子申报工作

为提高工作效率,方便医疗机构制剂再注册、调剂、委托配制等业务的申报,并降低申报成本、减少往返时间,广东省局药品注册处与省局信息中心合作,先后开发了医疗机构制剂再注册、调剂和医疗机构制剂委托配制三项业务网上无纸化申报及受理审批系统,开创了申报资料全部电子化并进行网上申报、受理、审批之先河,     

四川省医疗机构制剂发展现状及对策探讨

目的:为促进四川省医疗机构制剂的可持续发展提供参考。方法:通过分析四川省食品药品监督管理局2010-2013年发布的医疗机构制剂批件信息,介绍四川省医疗机构制剂的发展现状,对比医疗机构制剂与药品的注册特性,了解其发展趋势与存在的问题。结果与结论:2010-2013年,四川省共有医疗机构制剂2 989个,其中中药制剂2 441个(占81.67%),化学药制剂548个(占18.33%);分为33种剂型,根据数量排序列前6位的分别是丸剂、口服溶液剂、散剂、胶囊、颗粒剂、洗剂。目前,四川省医疗机构制剂存在品种和数量较多、剂型发展不平衡;质量标准拟定依据滞后,制剂室设备、设施较陈旧等问题。与药品的注册特性相比,医疗机构制剂为固定处方、配制工艺成熟、分布地域差异性较大;配制范围、使用范围都存在局限性;申报与审批要求低于药品;缺少确定工艺可行性的批量生产过程的配制现场检查;不良反应收集力度不足。建议充分发挥四川省的中药制剂特色优势,强化医疗机构制剂质量管理,建立长期、完善的抽验检查制度,构建区域制剂配制中心,实施医疗机构制剂室分类管理制度。     

山东省食品药品监督管理局关于发布山东省《医疗机构制剂注册管理办法(试行)》实施细则的通知

《山东省〈医疗机构制剂注册管理办法〉(试行)实施细则》于2005年8月1日经局务会议审议通过,现予发布,自发布之日起施行。附件:山东省《医疗机构制剂注册管理办法(试行)》实施细则山东省《医疗机构制剂注册管理办法》(试行)实施细则第一章总则第一条为加强医疗机构制剂的管理,规范医疗机构制剂的申报与许可行为,依据《医疗机构制剂注册管理办法》(试行),结合我省实际情况,制定本实施细则。第二条在山东省境内申请医疗机构制剂的配制、调剂使用以及进行相关的许可、检验和监督管理,适用本实施细则。第三条山东省食品药品监督管理局(以下简称…     

上海市社区卫生服务中心医务人员伦理学知识调查及建议

目的:调查上海社区卫生服务中心医务人员的伦理学知识认知情况.方法:采取分层抽样方式,于2016年6—8月对上海市245家社区卫生服务中心的7552名医务人员进行问卷调查.结果:医务人员对伦理学知识非常了解、基本了解、了解很少和完全不了解的人数分别为536人(7.1%)、5411人(71.7%)、1536人(20.3%)和69人(0.9%).不同岗位、职称、学历的医务人员之间存在着明显的伦理学知识认知差距.结论:上海社区卫生服务中心医务人员的伦理学知识了解程度仍有待提高,需加强伦理学知识的学习和应用.     

Nifedipine in the treatment of hypertension in the elderly

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.     

Studies on the receptors involved in the action of the various agents in the phenylbenzoquinone analgesic assay in mice

1. Tolerance to the activity of several narcotic analgesics (morphine, levorphanol, and methadone) and several narcotic-antagonist analgesics (pentazocine, cyclazocine, and nalorphine) was studied in the mouse phenylbenzoquinone stretching test. Virtually complete tolerance was induced by chronic treatment with each of the narcotic agents, while no apparent tolerance was induced by the narcotic antagonists.2. In morphine-tolerant mice there was a high degree of cross-tolerance to the effects of not only the other narcotic drugs but also to those of the narcotic antagonists, acetylsalicylic acid, and physostigmine.3. The effects of morphine and pentazocine were antagonized by naloxone but not by atropine, while the effects of physostigmine were antagonized by atropine but not by naloxone. Neither atropine nor naloxone antagonized the effect of acetylsalicylic acid.4. The results of the tolerance study suggest that there is a fundamental difference in the consequences of receptor interaction for the narcotic and the narcotic-antagonist analgesics. Morphine-tolerant mice exhibit cross-tolerance non-specifically. The selectivity of naloxone and atropine differentiates the narcotic and narcotic-analgesics from the other two agents used in this analgesic test.     

Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse

The ability of ⁹-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8,11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E₁ (PGE₁) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED₅₀ in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED₅₀ range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE₁ as the nociceptive agent, 11-OH THC was equipotent to THC while 8,11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.     

Neurotensin causes a greater increase in the metabolism of dopamine in the accumbens than in the striatum in vivo

Differential pulse voltammetry with carbon fibre electrodes was used to study the effect of central administration of neurotensin on the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum in anaesthetised rats. Intracerebroventricular injection of neurotensin (10 micrograms) increased the peak height for DOPAC 20 min after administration in the nucleus accumbens but only after 40 min in the striatum. The maximum increase was similar in both regions, with 30% and 27% above the pre-injection basal level, respectively. Neurotensin (1 micrograms) however increased the extracellular level of DOPAC in the nucleus accumbens alone. Neurotensin (0.1, 1.0 and 3.0 micrograms/0.5 microliter), injected into the ventral tegmental area, induced a potent and long-lasting elevation of the peak height for DOPAC in the nucleus accumbens, while the same doses in the substantia nigra produced effects on the metabolism of dopamine in the striatum of smaller amplitude and shorter duration. The maximum effect of each dose was about 2.5 times greater in the mesolimbic, compared to the nigrostriatal system. Amphetamine (2 mg/kg, s.c.) decreased the extracellular level of DOPAC with a similar magnitude, both in the nucleus accumbens (52%) and the striatum (47%). Intracerebroventricular administration of neurotensin (1 micrograms), 5 min after amphetamine, did not alter the effect of amphetamine on the extracellular level of DOPAC either in the nucleus accumbens or the striatum. However, neurotensin (10 micrograms) partially reversed the effect of amphetamine in the nucleus accumbens and had a similar but smaller and delayed effect in the striatum. The results from the present study, together with previous neurobehavioural studies, suggest that neurotensin has a relatively selective action on the mesolimbic dopaminergic system in the rat.     

Role of the liver in the disposition of intravenous nitroglycerin in the rat

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.     

女性医务人员健康状况的研究

目的探讨女性医务人员健康状况的特点。方法对2877例医院工作人员健康查体资料进行统计学分析。结果①女性医务人员中,41.0%的人员患有不同类型的疾病,略高于男性患病率（36.8%）,二者差异有统计学意义（P=0.029）;②女性医务人员高脂血症为31.9%（212/665）,低于男性（65.9%,274/416）;③脂肪肝患病率女性（32.6%,181/556）,亦低于男性（45.9%,151/329）;④女性相关疾病中,乳腺疾病和子宫肌瘤的患病率分别为4.8%和3.4%;而宫颈糜烂为20.2%;⑤女性医务人员高血糖为11.0%（77/702）,高血压为4.6%（56/1229）。结论女性医务人员中妇科与乳腺疾病是健康体检的重点,代谢性疾病也应加以关注。     

人文关怀在手术室护理中的应用

目的探讨在手术室护理中人文关怀的作用。方法将2012年5月至2012年11月200例手术患者随机分为两组,对照组100例,采取术前、术中常规护理,观察组100例,在对照组的基础上给予患者人文关怀,对比两组护理满意度及疗效。结果对照组各项指标满意度低于实验组(P<0.05),与对照组比较,实验组的住院时间明显缩短,痛苦小,并发症发生率低,P<0.05,差异均有统计学意义。结论 "以人为本"的人文关怀理念应用于手术室中,可充分提高护理质量及患者的满意度。