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??OBJECTIVE To prevent medication errors during drug subpackage and ensure patients?? medication safety.METHODS Healthcare failure mode and effect analysis (HFMEA) was applied to evaluate the potential failure modes and effects during drug repackaging and dispensing. Thereafter rectification measures was analyzed and carried out in order to prevent the recurrence of failure modes. Risk priority numbers (RPNs) before and after the implication of rectification measures were analyzed using paired t tests.RESULTS After the application of healthcare failure mode and effect analysis, RPN was statistically significantly (P<0.05) reduced by 60% (P=0.000 2), which affecting the incidences of medication errors during drug unit-dose repackaging.CONCLUSION The application of healthcare failure mode and effect analysis can effectively prevent medication errors during drug subpackage and improve patients?? medication safety.     

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??OBJECTIVE To study and analyze FDA issued guidance on Bioequivalence Recommendations for Specific Products related with long Half-life drugs. METHODS Bioequivalence Recommendations for Specific Products related with long Half-life drugs was analyzed from multiple aspects, including bioequivalence study designs, selection of bioequivalence subjects, dosage, selection of reference products, analytes to measure, bioequivalence waiver on multiple-strength products and implementation of the Biopharmaceutics Classification System. RESULTS Bioequivalence Recommendations for Specific Products issued by FDA are to further facilitate generic drug product availability and to assist generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating evidence needed to support ANDA approval or reassessment, as an extension and implement to the guideline involved in the aspect of bioequivalence. CONCLSUTION Bioequivalence Recommendations for Specific Products issued by FDA would provide instructive and practical assists to the equivalence assessment of quality and curative effect for generic products in China, since there is not corresponding bioequivalence guidance on specific long Half-life drugs released by CFDA yet.     

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??OBJECTIVE To observe the clinical effect of hyaluronic acid fillers in the personality injection methods of nasolabial folds. METHODS Anesthesia was obtained with a topical anesthesia peel off mask of lidocaine. Hyaluronic acid was injected into the tissue with hypodermic or blunt-tip needle. The volume injected was variable, depending on the depth and the extent of the defect. RESULTS AND CONCLUSION 236 Patients were treated from 2013 to 2017. Using different injection methods of hyaluronic acid fillers to improve nasolabial folds could produce less complication and higher satisfaction.     

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??OBJECTIVE To develop an HPLC method for simultaneous determination of seven tannins in Chebulae Fructus, including gallic acid, chebulic acid, corilagin, ethyl gallate, ellagic acid, chebulagic acid and 1,2,3,4,6-O-pentagalloylglucose and determine the contents of the seven tannins in Chebulae Fructus Retz from different areas.METHODS The HPLC analysis was carried out on an Hypersil ODS2 C₁₈ (4.6 mm??250 mm,5 ??m) column with acetonitrile (A) and 0.05% formic acid solution in water (B) as mobile phase in a linear gradient elution mode. The UV detection wavelength was set at 290 nm and the flow rate was 1.0 mL??min^-1.RESULTS The calibration curves of the seven tannins all showed good linearity (r??0.999 8). The recovery rates were in the range of 95.2% to 98.4%. All the seven tannins could be detected in the two kinds of Chebulae Fructus Retz from eight regions, but the amounts of these tannins varied significantly. The contents of the seven tannins active ingredients in Chebulae Fructus of Terminalia chebula Retz from Hainan, Guangxi, Guangdong and Xinjiang were much higher than those from other areas, while those in Chebulae Fructus of Terminalia chebula Retz. var. tomentella Kurt were higher in Guangdong and Guangxi than other areas.CONCLUSION The method is proved to be accurate and valid, and can be used for the quality control of Terminalia chebula Retz.     

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??OBJECTIVE To provide a theoretical basis for scientific and rational use of paclobutrazol in the production of Ophiopogonis Radix. METHODS Different concentrations of paclobutrazol were applied to Ophiopogonis Radix plants, and medicinal samples were colleted. The efficacy of Ophiopogonis Radix were comprehensively analyzed from the appearance of the herb and the contents of three kinds of effective components: flavonoids, saponins, and polysaccharides. Residues of paclobutrazol were detected. The effect of paclobutrazol use on the safety of Ophiopogonis Radix was evaluated according to the acceptable daily intake (ADI) of paclobutrazol in the GB2763-2014 and the amount of usage of paclobutrazol required by Chinese Pharmacopoeia. RESULTS Paclobutrazol had no significant effects on the Ophiopogonis Radix appearance; and the contents of polysaccharides and flavonoid were increased in varying degrees, and saponins content were decreased. The daily intake of paclobutrazol was far less than the ADI (0.1 mg??kg^-1?? body weight) when calculated using the maximum residue of paclobutrazol at the usage of 3 kg??acres^-1 and the maximum usage amount of Ophiopogonis Radix in Chinese Pharmacopoeia. CONCLUSION Paclobutrazol can be used within limits according to the actual situation in Ophiopogonis Radix production.     

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??OBJECTIVE To develop on-line high performance liquid chromatography-biochemical detection (HPLC-BCD) methods to screen effective components in Ginkgo biloba extract for treatment of Alzheimer's disease. METHODS Radical scavengers and AchE inhibitors in G.biloba leave extract were screened by HPLC-UV-DPPH/ABTS and HPLC-UV-AchE methods, respectively. The stability and repeatability of the on-line HPLC-UV-AchE method were investigated using galanthamine as a positive reference. The main active ingredients in the extract were identified by ultra high performance liquid chromatography linear ion trap/orbitrap high resolution mass spectrometry (UPLC-LTQ/orbitrap MS) method. RESULTS Fourteen antioxidants in G.biloba extract were detected by the HPLC-UV-DPPH/ABTS method, while three AchE inhibitors were found by the HPLC-UV-AchE method. The three AchE inhibitors were tentatively identified by UPLC-LTQ/orbitrap MS as 4-O-beta-glucopyranosyl-cis-coumaric acid?? ginkgolide A and 3-O-[2-O-(β-D-Glucosyl)-α-L-rhamnosyl]quercetin, respectively. CONCLUSION The proposed on-line HPLC-BCD method shows high sensitivity, good repeatability and stability. It can be used to screen antioxidants and AchE inhibitors in G. biloba extract. This will provide an effective, quick and convenient analysis tool to quickly find bioactive ingredients of traditional Chinese medicines for treating related diseases.     

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??OBJECTIVE To retrospectively study the clinical efficacy and safety of sulbactam sodium in treatment of extensively drug resistant Acinetobacter baumannii(XDRAB) infection.METHODS Collect cases of XDRAB infection treated with sulbactam Sodium in our hospital from January 2014 to January 2016. Basic information of patients, infection sites, therapeutic strategies, drug combination, clinical outcomes and adverse reactions were analyzed retrospectively.RESULTS A total of 7 cases were collected, including 4 cases of pulmonary infection, 2 cases of intracranial infection, 1 case of abdominal infection, therapeutic strategies for sulbactam sodium-based combination therapy. The total mortality rate was 42.8%; 1 case showed adverse drug reactions may correlated with sulbactam sodium.CONCLUSION Mortality associated with XDRAB infection is high,and the clinical outcome is associated with host factors, because this article included in the number of cases is less, so difficult to evaluate the effectiveness of sulbactam sodium. Sulbactam sodium can be associated with other antimicrobial drugs for the treatment of XDRAB infection and provided more choices.     

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??OBJECTIVE To establish an HPLC-MS method for the analysis of the impurity profile of cefotaxime sodium. METHODS Shimadzu-LCMS-IT-TOF was used with Waters XBridge Shield (RP18,4.6 mm??250 mm, 5 ??m) column. Mobile phase A was 20 mmol??L^-1 ammonium acetate (pH adjusted to 6.25)-methanol (92:8), and mobile phase B was set at 20 mmol??L^-1 ammonium acetate-methanol (60:40) (pH adjusted to 6.25).Gradient elution was performed at a flow rate of 1.0 mL??min^-1. ESI source was used.Positive and negative ion scanning was conducted in the range of m/z 150-900.The heating temperature was 200 ??, CDL temperature was maintained at 200 ??, atomization gas flow rate was 1.5 L??min^-1, dry gas pressure was 94.0 kPa, and the post-column diversion ratio was 1:4.Some related substances in cefotaxime sodium were identified by comparing the retention time in chromatography,[M+H]⁺ spectrum and MS² spectrum with those of reference substances, the others which haven't reference substances were deduced or speculated by analyzing the MS² or MSⁿ fragmentation with the help of a rule summarized from the MS² fragmentation of cefotaxime sodium and the reference substances of system suitability impurities. RESULTS Twenty-six related substances were separated and detected in the sample, all of which were identified or deduced. They were cefotaxime sodium isomeric compounds and homologs generated during the production process or degradation products. CONCLUSION The method can be applied in the identification and qualitative analysis of the related substances of cefotaxime sodium and the quality control and optimization of the synthesis of cefotaxime sodium.     

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??OBJECTIVE To synthesize a prodrug of paclitaxel which is modified by palmitic acid at the 2??-hydroxyl position and prepare paclitaxel palmitate liposomes(PTX-PA-L), and then compare the pharmacodynamics and safety of PTX-PA-L in S180 tumor-bearing rats with paclitaxel injection. METHODS The derivative of paclitaxel was synthesized using 4-dimethylaminopyridine(DMAP) as acid binding agent and 1-(3-dimethylaminopropyl)-3-ethylenediamine(EDC) as dehydrating agent. PTX-PA was characterized by mass spectrometry and nuclear magnetic resonance spectroscopy(600 MHz ¹H-NMR). PTX-PA-L were prepared using film dispersion-ultrasonic method. The particlesize and Zeta potential were measured using Malvern Zeta-sizer Nano S and the morphologywas characterized by TEM. The S180 sarcoma model in ICR mice was established to study the antitumor efficiency of PTX-PA-L in vivo. The hematological toxicity and body weight change of the mice were evaluated to study the safety of PTX-PA-L. RESULTS The prodrug PTX-PA was synthesized successfully. The liposomes had good morphological characteristics and light blue opalescence and the particle size was(104.82??1.23) nm. The pharmacodynamic study showed that compared with paclitaxel injection, PTX-PA-L had better antitumor efficacy on S180 tumor-bearing mice and the blood index indicated less decrease of white blood cells and neutrophils. CONCLUSION PTX-PA-L can improve the antitumor efficacy significantly and reduce the toxicity of paclitaxel injection.     

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??OBJECTIVE To develop a method suitable for rapid and accurate analysis of triacylglycerols in medium/long chain structured triacylglycerols by ultraperformance convergence chromatography combined with a quadrupole time-of-flight mass spectrometry. METHODS The separation was performed at 28 ?? on a Waters Acquity UPCC system by anHSS C₁₈ SB column (3.0 mm??150 mm,1.8 ??m) with gradient elutionof CO₂ and methanol acetonitrile (7??3, V/V),the flow rate was 1.2 mL??min^-1, the back pressure was 117.2 MPa, and methanol containing 0.1% formic acid and 2 mmol??L^-1 ammonium formate was used as supplement solvent. Positive ion electrospray ionisation (ESI) mode and MS^E technology were used in which two separate scan functions were programmed for the MS acquisition. The qualitative analyses were carried out by using precise mass information of parent ions and product ions. RESULTS A total of 52 triacylglycerols were obtained and their stuctures were identified by analyzing the precise mass information of their parent ions and product ions respectively. CONCLUSION The method is simple,highly accurate, and environmental friendly with good resolution, and can be used for rapid and accurate analysis of medium/long chain triacylglycerols excipients.     

葡萄糖修饰脑靶向紫杉醇脂质体包封率测定方法的比较

目的:建立葡萄糖修饰脑靶向紫杉醇脂质体的包封率测定方法,为该制剂的质量控制提供参考。方法:采用薄膜分散法制备脂质体。采用RP-HPLC测定紫杉醇的含量,流动相甲醇-水(70∶30),检测波长228 nm,流速0.8 m L·min-1。利用RP-HPLC测定胆固醇的含量,流动相甲醇,检测波长210 nm,流速1 m L·min-1。采用凝胶柱色谱法、鱼精蛋白沉淀法、滤膜法、透析法分离脂质体与游离药物,比较4种方法测定包封率的可行性。结果:紫杉醇与胆固醇含量测定方法的专属性、精密度、稳定性和回收率试验均符合测定要求,线性范围分别为0.4~100,1~500 mg·L-1。4种方法紫杉醇与脂质体回收率均介于95%~105%,满足脂质体包封率测定的要求;包封率分别为74.68%,92.91%,95.14%,95.08%。结论:鱼精蛋白沉淀法操作简单、快捷,几乎不受脂质体粒径的影响,适用于紫杉醇脂质体包封率的测定。     

白藜芦醇脂质体对C6胶质瘤细胞的抑制作用分析

目的:制备白藜芦醇脂质体并对其体外抗肿瘤作用进行评价。方法:通过薄膜分散-硫酸铵梯度法制备白藜芦醇脂质体,使用粒度仪对脂质体进行表征;确定C6胶质瘤细胞对数生长期;通过磺酰罗丹明B蛋白(SRB)法评价游离白藜芦醇及其脂质体对C6胶质瘤细胞的抗增殖作用,利用流式法考察白藜芦醇及其脂质体对C6胶质瘤的凋亡作用,以及C6胶质瘤细胞对白藜芦醇和其脂质体的摄取作用。结果:白藜芦醇脂质体的平均粒径(139.97±0.64)nm,Zeta电位(-7.00±0.74)m V;游离白藜芦醇和白藜芦醇脂质体对C6胶质瘤细胞的抑制率最高分别可达(73.30±0.56)%和(91.70±0.60)%,差异有统计学意义(P0.05);游离白藜芦醇和白藜芦醇脂质体对C6胶质瘤细胞的诱导凋亡率分别为(20.03±0.85)%和(27.18±0.96)%,差异有统计学意义(P0.05);C6胶质瘤细胞对游离白藜芦醇和白藜芦醇脂质体的摄取率分别为(67.79±1.19)%和(77.61±1.67)%。结论:相比于游离的白藜芦醇,白藜芦醇脂质体对C6胶质瘤细胞的抗增殖作用更明显,具有更强的诱导C6胶质瘤细胞凋亡作用。白藜芦醇脂质体可以更多地被C6胶质瘤细胞摄取,这在一定程度上促进了其对C6胶质瘤细胞的抗增殖作用和诱导凋亡能力。说明白藜芦醇脂质体具有较强的体外抗C6胶质瘤作用。     

肝细胞靶向甘草次酸表面修饰脂质体的制备

目的 :研制靶向于肝细胞的甘草次酸表面修饰脂质体。方法 :化学合成 3-琥珀酸-30-硬脂醇甘草次酸酯 (Suc-GAOSt)作为导向分子 ,采用乙醇注入法制备甘草次酸表面修饰脂质体 (LP-SM-GA)。结果 :Suc-GAOSt确能掺入脂质膜中 ,掺入比例最高可达总脂质的9%。结论 :LP-SM-GA制备成功 ,可作为肝细胞主动靶向给药的潜在途径。     

肺靶向羟基喜树碱脂质体的制备及体外释药性质研究

 目的研究肺靶向羟基喜树碱阳离子脂质体的制备方法并考察其体外释药性质。方法采用薄膜-冻融法制备羟基喜树碱脂质体;用D-甘露糖修饰脂质体并添加适量十八胺调节脂质体表面电荷;用葡聚糖凝胶柱-高效液相色谱法测定包封率;用正交实验优选处方;用透析法考察药物体外释放性质。结果制得的脂质体平均粒径为2.286μm,表面电荷为+21.5 mV,包封率大于65%,稳定性好。药物体外释药符合Higuchi方程。结论采用薄膜-冻融法,用D-甘露糖修饰并添加十八胺可制得具有较高包封率及稳定性的羟基喜树碱脂质体,有助于提高羟基喜树碱的肺靶向性。     

胆盐脂质体的制备及理化性质研究

 目的以脱氧胆酸钠(sodium deoxycholate,DOC)为模型胆盐,制备胆盐脂质体,并对其理化性质进行研究。方法采用逆向蒸发法制备胆盐脂质体,以钙黄绿素为模型药,以胆盐脂质体在20mmol·L^-1胆盐中的稳定性为指标,考察总脂量、胆固醇与磷脂比、脱氧胆酸钠与脂相的摩尔比等处方因素。采用优化后的处方,考察胆盐脂质体的外观形态,粒径分布及脱氧胆酸钠在胆盐脂质体中的分布情况。结果处方优化后,总脂量、胆固醇与磷脂比及脱氧胆酸钠与脂相的摩尔比应分别为225mg,0.5(w/w)和0.5(mol)。外观形态良好,粒径分布均匀。有效胆盐磷脂摩尔比(Re)为0.26,脱氧胆酸钠在脂相的分配系数(K)为0.21mmol^-1。结论处方优化后制备得到的胆盐脂质体的稳定性较好。     

N-三甲基壳聚糖包衣多柔比星脂质体的体外血管内皮细胞靶向性研究

 目的 以脐静脉内皮细胞（HUVECs）为模型,考察其对N-三甲基壳聚糖（TMC）包衣的盐酸多柔比星脂质体的摄取情况, 以评价TMC包衣盐酸多柔比星脂质体的体外血管内皮细胞靶向性。方法 采用pH梯度法制备盐酸多柔比星脂质体,以不同取代度的TMC进行包衣,用DAPI定位细胞核,采用激光扫描共聚焦荧光显微镜观察不同TMC包衣盐酸多柔比星脂质体在HUVECs胞浆及胞核的转运及摄取情况。结果 盐酸多柔比星脂质体性质稳定,包封率均在80%以上,粒径在100～200 nm, 随着TMC季铵化程度的增大,TMC包衣盐酸多柔比星脂质体的Zeta电位显著增大(P<0.05),同时HUVECs对其摄取能力增强,多柔比星能较快释放到胞浆并转运至胞核。结论 TMC包衣盐酸多柔比星脂质体具有较强的体外内皮细胞靶向作用,且与TMC的季铵化程度有关,为进一步研究其体内靶向作用奠定了基础。     

姜黄素眼用脂质体的制备及晶状体抗氧化作用考察

目的：制备N-三甲基壳聚糖（TMC）包覆姜黄素眼用脂质体并考察其抑制大鼠硒性白内障晶状体氧化作用。方法：采用乙醇注入法制备姜黄素脂质体（Cur-TCL）,通过星点设计-效应面法优化脂质体处方工艺;采用过膜法、透射电镜、粒径电位测定仪测定Cur-TCL的理化性质;建立大鼠硒性白内障模型,考察Cur-TCL对白内障形成过程中晶状体氧化的抑制作用。结果：最佳处方为姜黄素1.41 mg,磷脂质量分数4%,胆固醇-磷脂（1：5.44）。经0.5%TMC溶液包覆后脂质体呈球形,粒径增大,电位显著提高,药物包封率基本不变。与未包覆脂质体相比,Cur-TCL组大鼠晶状体中SOD活力提高30.3%,MDA摩尔浓度减少52.4%,GSH含量增加1.29倍。结论：Cur-TCL可显著抑制硒性白内障导致的晶状体氧化过程,为该制剂治疗白内障提供参考。     

盐酸表柔比星长循环热敏脂质体的处方优化及体外释药考察

目的制备盐酸表柔比星长循环热敏脂质体(EPI-LTSL)并进行处方优化,考察其体外热敏释药性质。方法pH梯度法制备EPI-LTSL,葡聚糖凝胶法分离脂质体和游离药物以测定包封率,HPLC测定药物含量。进行优化处方,采用荧光淬灭法测定脂质体的体外热敏释药率。结果优选处方制备的EPI-LTSL为半透明橘红色,磷脂质量浓度为75mg.mL-1,二棕榈酰磷脂酰胆碱(DPPC)-肉豆蔻酰溶血磷脂酰胆碱(MSPC)摩尔比为82:8;药脂比为1:10,平均粒径小于100nm,载药量大于2mg.mL-1,包封率99%,相变温度为42.76℃。EPI-LTSL37℃水浴15min的累积释药小于5%,而43℃水浴4min的累积释药达到90%以上。结论制备的EPI-LTSL载药量和包封率较高、粒径较小,热敏释药性质良好。采用荧光淬灭法测定EPI-LTSL体外热敏释药率准确快捷。     

圣和散对脑胶质瘤细胞诱导分化的研究

目的观察圣和散对脑胶质瘤C6细胞株体外生长及诱导分化的作用。方法用圣和散处理脑胶质瘤C6细胞,采用甲基噻唑基四唑(MTT)比色法检测圣和散对C6细胞增殖的抑制作用,以免疫组化SABC法检测胶质纤维酸性蛋白(GFAP)和c-myc表达。结果圣和散可显著抑制C6细胞体外增殖,并呈现时间、剂量依赖性。在终浓度为5 mg/ml和10 mg/ml时,对C6增殖的抑制率达(49.62±1.13)%和(69.38±1.42)%,明显优于对照组(P<0.01)。免疫组化可见SHP组较对照组GFAP表达明显增强,c-myc表达下降。结论圣和散对胶质瘤C6细胞系的增殖有明显的抑制作用,能通过诱导分化降低脑胶质瘤细胞恶性程度。     

甘草次酸衍生物配体18-GA-Ala介导脂质体的制备及肝靶向性研究

目的：合成制备甘草次酸衍生物配体丙氨酸丁二酸甘草次酸十八烷酯（18-GA-Ala）,并修饰包埋药物丹酚酸B (Sal B)和丹参酮ⅡA(TSN)的脂质体,探讨该脂质体对小鼠的肝靶向作用。方法：采用薄膜分散-高压乳匀法制备18-GA-Ala配体修饰的TSN-Sal B脂质体及未修饰配体的脂质体,考察粒径、电位、包封率、多分散系数和配体结合率;尾静脉给药后不同时间点获取血浆样本及小鼠心、肝、脾、肺、肾组织样本,超高效液相色谱法测定各样本中Sal B和TSN的含量,评价18-GA-Ala配体的肝靶向效果。结果：配体18-GA-Ala修饰后的脂质体中,Sal B在肝脏的药时曲线下面积（AUC）分别是脾、肺和肾的1.19、1.39、63.67倍,TSN在肝脏的AUC分别为脾、肺、肾的4.64、0.36、14.12倍。结论：甘草次酸衍生物配体18-GA-Ala修饰后的脂质体可增加Sal B和TSN在肝脏中的峰浓度,表现出一定的肝靶向作用。