国外仿制药参比制剂选择简介及对我国的启示

目的：为完善我国仿制药一致性评价中参比制剂选择机制和程序提供参考,为仿制药企业在应用选择参比制剂时提供思路。方法：详细介绍了美国FDA有关参比制剂选择指南草案的最新描述,以及欧盟、日本和WHO对于参比制剂的相关要求。结合我国现阶段仿制药一致性评价工作实际,为完善参比制剂选择程序提出建议。结果与结论：美国详细规定了仿制药参比制剂的选择思路和实际操作程序,为我国仿制药参比制剂的选择提供了新的思路。我国正处于仿制药一致性评价参比制剂遴选的关键时期,制定全面、完善的参比制剂遴选体系和机制,有助于规范参比制剂的选择程序,加快一致性评价工作进程,提升我国仿制药一致性评价参比制剂选择的科学性和完整性。     

Medical service provider networks

In many countries, health insurers or health plans choose to contract either with any willing providers or with preferred providers. We compare these mechanisms when two medical services are imperfect substitutes in demand and are supplied by two different firms. In both cases, the reimbursement is higher when patients select the in‐network provider(s). We show that these mechanisms yield lower prices, lower providers' and insurer's profits, and lower expense than in the uniform‐reimbursement case. Whatever the degree of product differentiation, a not‐for‐profit insurer should prefer selective contracting and select a reimbursement such that the out‐of‐pocket expense is null. Although all providers join the network under any‐willing‐provider contracting in the absence of third‐party payment, an asymmetric equilibrium may exist when this billing arrangement is implemented.     

The cost-effectiveness of trivalent and quadrivalent influenza vaccination in communities in South Africa,Vietnam and Australia

BackgroundTo inform national healthcare authorities whether quadrivalent influenza vaccines (QIVs) provide better value for money than trivalent influenza vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and-middle income communities based in South Africa and Vietnam and contrasted these findings with those from a high-income community in Australia.MethodsIndividual based dynamic simulation models were interfaced with a health economic analysis model to estimate the cost-effectiveness of vaccinating 15% of the population with QIV or TIV in each community over the period 2003–2013. Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+ years and young children. Country or region-specific data on influenza-strain circulation, clinical outcomes and costs were obtained from published sources. The societal perspective was used and outcomes were expressed in International$ (I$) per quality-adjusted life-year (QALY) gained.ResultsWhen compared with TIV, we found that QIV would provide a greater reduction in influenza-related morbidity in communities in South Africa and Vietnam as compared with Australia. The incremental cost-effectiveness ratio of QIV versus TIV was estimated at I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in Australia.ConclusionsThe cost-effectiveness of QIV varied between communities due to differences in influenza epidemiology, comorbidities, and unit costs. Whether TIV or QIV is the most cost-effective alternative heavily depends on influenza B burden among subpopulations targeted for vaccination in addition to country-specific willingness-to-pay thresholds and budgetary impact.     

艾叶的化学成分、药理作用及产品开发研究进展

艾叶为我国传统中药材,主要含有挥发油、黄酮、多糖、鞣酸、萜类及微量元素等多种化学成分。其药理作用较为广泛,包括抗菌、抗病毒、抗氧化、保肝利胆、止血及抗凝血、抗过敏、免疫调节、抗癌等。目前其应用集药品、食品、保健品等于一体,具有广阔的开发前景。对艾叶的化学成分、药理作用及产品的开发研究进展做一概述,为更合理有效地利用艾叶药材、开发艾叶产品提供参考。     

FDA对皮肤外用药活性成分人体最大用量试验的要求

美国食品药品管理局（FDA）于2018年5月发布了“考虑列入OTC专论的外用药活性成分的最大用量试验：研究要点和考虑的因素供企业用的指导原则”。最大用量试验（MUsT）是评估外用药体内生物利用度的标准方法,该指导原则对MUsT许多研究要点提出了具体的建议。详细介绍该指导原则的主要内容,期待对我国这方面的研究和监管有益。     

抗风湿类中成药及保健品中非法添加双氯芬酸钠的快速筛查方法研究

目的建立抗风湿类中成药和保健品中非法添加双氯芬酸钠的快速筛查方法。方法采用一种化学方法进行快速筛查,同时建立高效液相色谱法测定含量,并用高效液相色谱-二极管阵列检测器和超高效液相色谱-串联三重四级杆质谱联用仪对样品进行确证。结果 50批样品中共检出15批阳性样品,漏检率为0,误检率为0,正确率为100%,阳性样品含量分别在7⁴0 mg/粒。结论本快筛方法灵敏度高,专属性强,操作简便快捷,环保安全,经济适用,适用于基层单位的快速筛查。     

HPLC测定坎地沙坦酯氨氯地平片有关物质及降解产物

目的 建立测定坎地沙坦酯氨氯地平片有关物质的高效液相色谱法。方法 采用Inertsil ODS-SP C18（150 mm× 4.6 mm,5 μm）色谱柱,以0.035 mol·L-1 KH2PO4（磷酸调pH 3.0）-甲醇-乙腈为流动相,梯度洗脱,检测波长238 nm,流速1.0 mL·min-1。结果 特异性杂质和破坏条件下产生的降解产物与主药分离较好,3批样品最大单个杂质为坎地沙坦酯杂质B,总杂质均〈0.5%。结论 本法专属性强,灵敏度高,重现性好,能够有效控制产品质量。     

天然产物分离中高速逆流色谱溶剂体系的研究进展

根据溶剂体系的极性与分离的天然产物的关系,本文对高速逆流色谱中使用的溶剂系统进行了归纳总结,不仅对快速选择溶剂体系分离天然产物起到了一定的指导作用,而且为今后高速逆流色谱溶剂体系的研究提供了方便。     

Triclabendazole Effect on Protease Enzyme Activity in the Excretory- Secretory Products of Fasciola hepatica in Vitro

Background

Fasciola hepatica is one of the most important helminthes parasites and triclabendazole (TCBZ) is routinely used for treatment of infected people and animals. Secreted protease enzymes by the F. hepatica plays a critical role in the invasion, migration, nutrition and the survival of parasite and are key targets for novel drugs and vaccines. The aim of study was to determine the protease activity of excretory- secretory products (ESP) of F. hepatica in the presence of TCBZ anthelmintic.

Methods

F. hepatica helminthes were collected and cultured within RPMI 1640 [TCBZ treated (test) and untreated (control)] for 6 h at 37 °C. ESP of treated and control were collected, centrifuged and supernatants were stored at -20°C. Protein concentrations were measured according to Bradford method. Protease enzymes activities of ESP samples were estimated by using sigma’s non-specific protease activity assay. ESP protein bands were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Results

Mean protein concentrations in control and treated of ESP samples were determined 196.1 ±14.52 and 376.4 ±28.20 μg/ml, respectively. Mean protease enzymes activities in control and treated were 0.37 ±0.1 and 0.089 ±0.03 U/ml, respectively. Significant difference between proteins concentrations and protease enzymes activities of two groups was observed (P<0.05). SDS-PAGE showed different patterns of protein bands between treated and control samples.

Conclusion

The TCBZ reduced secreted protease enzymes activities and possibly effects on invasion, migration, nutrition and particularly survival of the parasite in the host tissues.