采用原研制剂制备米诺膦酸片及体外溶出度的一致性考察

制备米诺膦酸片,并以原研制剂为参比制剂,采用f2相似因子法对两者体外溶出度的一致性进行考察.建立合适的体外溶出度测定方法,研究参比制剂的溶出情况,通过单因素试验对辅料的用量进行筛选,制备出米诺磷酸片.比较自制品与原研制剂在不同溶出介质中的溶出行为,评价两者体外溶出行为的相似性.结果表明:制备的米诺膦酸片剂与原研制剂在4种不同pH值溶出介质中的溶出相似因子f2均大于50;制备的米诺膦酸片剂与原研制剂体外溶出行为相似.国家自然科学基金资助项目(81302652);;福建省自然科学基金资助项目(2015J01342

半富马酸替诺福韦艾拉酚胺的合成工艺优化

对最新抗乙肝药物半富马酸替诺福韦艾拉酚胺（TAF）的合成工艺进行优化研究.以腺嘌呤（1）为原料,与（R）-碳酸丙烯酯反应得到（R）-9-（2-羟丙基）腺嘌呤.然后,将产物经磷叶立德取代,水解反应得到（R）-9-（（2-磷酸单苯酯基）甲氧基）丙基)-腺嘌呤.最后,将所得产物经取代、酰化、缩合、成盐反应得到目标产物TAF,并对各步反应条件进行优化.结果表明:总收率达32.1%（以腺嘌呤计）,较原工艺提高23.1%,目标化合物及主要中间体经电子轰击质谱（EI-MS）、核磁共振氢谱（1H-NMR）、核磁共振碳谱(13C-NMR)确证结构;与现有文献报道的TAF合成工艺相比,优化后的工艺总收率大幅提高,反应成本降低,反应时间缩短,可避免生产过程中的安全隐患,适合工业化生产.国家重点研发计划项目(2016YFE0101700

Preparation of pDNA-Loaded Thiolated Chitosan Nanoparticles and Optimization by Using Box-Behnken Design and Response Surface Method

以巯基壳聚糖（TCS）为基因载体,采用离子交联法制备能用于基因口服研究的质粒DNA-巯基壳聚糖纳米粒（pDNA-TCS-NPs）.分别以TCS质量浓度、三聚磷酸钠（TPP）质量浓度、pH值和转速为考察对象,以pDNA-TCS-NPs粒径和Zeta电位为评价指标,采用4因素3水平Box-Behnken效应面法筛选最佳制备工艺,并对其外观形态,包封率等体外性质进行考察.结果表明：TCS质量浓度为0.80mg·mL（-1）,TPP质量浓度为0.65mg·mL（-1）,pH=5.3,转速为2 000r·min（-1）是最优制备工艺,可制得粒径为（134.21±1.34）nm,Zeta电位为（24.36±0.29）mV,包封率在（80.26±0.56）%,形状规则且分散良好的pDNA-巯基壳聚糖纳米粒;Box-Behnken实验设计可用于预测和优化pDNA-TCS-NP制备工艺优化筛选.Preliminary exploration to prepare plasmid DNA-loaded thiolated chitosan nanoparticles（pDNATCS-NPs）which can be used for gene oral administration was investigated.Using TCS as gene carriers,the pDNA-TCS-NPs were prepared by the ionic cross-linking method.The effects of the concentrations of TCS and TPP,pH value and stirring speed were investigated on the particle diameter and zeta potential of the pDNA-TCS-NPs.In addition,the formula was optimized by Box-Behnken design and response surface method with four factors and three levels,and the physic-chemical properties such as the shape and encapsulation efficiency were also studied.The results showed that the optimal formula was as follows：TCS concentration 0.80mg·mL（-1）,TPP concentration 0.65mg·mL（-1）,pH 5.3,and stirring speed 2 000r·min（-1）.Particle diameter was（134.21±1.34）nm,zeta potential was（24.36±0.29）mV,and efficiency was（80.26±0.56）%.under the optimal conditions.The pDNA-TCS-NPs showed uniform spherical solid particles with regular shape and ideal uniformly dispersion.It′s also confirmed that the Box-Behnken experimental design and response surface method could be used to predict and optimize the pDNA-loaded TCS nanoparticles.国家自然科学基金资助项目（81302652）;福建省自然科学基金资助项目（2015J01342

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies