Table of Content

    31 October 2014, Volume 23 Issue 10
    Journal of Chinese Pharmaceutical Sciences
    2014, 23(10):  663-666. 
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    Original articles
    The use of cationic liposomes to co-deliver docetaxel and siRNA for targeted therapy of hepatocellular carcinoma
    Jingquan Li, Zhenzhen Yang, Tingting Meng, Xianrong Qi
    2014, 23(10):  667-673.  DOI: 10.5246/jcps.2014.10.085
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    Hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel (DTX) and small interfering RNA (siRNA). The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.

    Hemocompatibility and cytocompatibility of diblock copolymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-based micelles
    Shujin Ma, Yanfang Li, Yong Zhao, Yanxia Zhou, Jinwen Li, Yajie Gao, Yushu Li, Xinru Li, Yan Liu, Xinglin Wang
    2014, 23(10):  674-680.  DOI: 10.5246/jcps.2014.10.086
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    A synthetic diblock copolymerpoly(2-ethyl-2-oxazoline)-poly(D,L-lactide) (PEOz-PLA) can self-assemble into micelles with an increased efficiency of drug delivery. However, the interactions of blood-micelles and cell-micelles remain unclear. In the present study, we aimed to assess the hemocompatibility and cytocompatibility of PEOz-PLA micelles in order to clarify its potentials as carriers for drug delivery. Blood compatibility of the micelles was evaluated by hemolysis analysis, coagulation test, platelet activation investigation and assessment of their interaction with protein. The results revealed that PEOz-PLA micelles had a favorable blood compatibility. In addition, PEOz-PLA micelles showed a good cytocompatibility through SRB assay, presenting only negligible cytotoxicity when incubated with KBv cells. Taken together, PEOz-PLA micelles could be used as a hemocompatible andcytocompatible drug carrier for intravenous administration.

    Discovery of novel dithiocarbamic acid ester HGWJ-11C with significant anticancer action
    Bin Liu, Jun Wei, Yiqiang Wang, Zemei Ge, Runtao Li
    2014, 23(10):  681-687.  DOI: 10.5246/jcps.2014.10.087
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    To find novel lead compound, seventy-four compound libraries were built through two rounds by a solution-phase CC on the basis of our developed method for the synthesis of dithiocarbamic acid ester. After evaluation for the antitumor activitiesof libraries, six compounds were selected to be synthesized and examined their antitumor activities. It was found that compound 13 (HGWJ-11C) with novel structure exhibited significant antitumor activities and the scaffold of dithiocarbamic acid was very crucial for the antitumor activity. The compound 13 is worth studying deeply as a potent hit compound.

    Total synthesis of a hydrated aurone derivative
    Aili Song, Chao Wang, Yanfen Wu, Lidong Zhou
    2014, 23(10):  688-693.  DOI: 10.5246/jcps.2014.10.088
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    Thetotal synthesis of a hydrated aurone derivative, 2-benzyl-4-methoxy-2,6-dihydroxybenzofuran-3(2H)-one,has been achieved for the first time with 2.4% overall yield. Using phloroglucinol as the starting material, the key steps included Friedel-Crafts acylation, Williamson synthesis, hydrogenolysis, aldol condensation, enolization and Rubottom oxidation.

    Separation and characterization of degradation/interaction products of codeine phosphate in ibuprofen arginate/codeine phosphate combination formulation by HPLC coupled with MS analysis
    Soumia Cheddah, Taijun Hang
    2014, 23(10):  694-710.  DOI: 10.5246/jcps.2014.10.089
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    A simple HPLC method was developed and validated according to the ICH guidelines to detect and quantify the related substances of codeine phosphate in the raw material and in its combination formulation with ibuprofen before and after forced degradation. These products were further identified by using HPLC-TOF/MS and MS/MS techniques. Good separations were obtained on a C18 (250 mm×4.6 mm, 5 µm) column maintained at 50 °C with linear gradient elution by a mixture of mobile phase A (ammonium acetate (pH 6.0 regulated with acetic acid, 0.04 M)acetonitrile (92:8, v/v)) and mobile phase B (acetonitrile) at a flowrate of 1 mL/min. UV detection was set at 245 nm. Codeine was found to be instable under oxidation with the production of mainly two stereoisomers of codeine N-oxide. A new degradation product, not reported previously, was detected under alkaline hydrolysis, which was identified as 6-hydroxy-3-methoxy-17-methyl-7,8-didehydromorphinan-5-ol and shortly named as deshydrolevomethorphandiol. The esterification of codeine by ibuprofen occurred in very small amount and only under acidic stress. These results contribute to the understanding of the degradation behavior of codeine and its interaction with ibuprofen. The developed method is sensitive and precise and could be applied for the quality control of codeine bulk drug, preparations of codeine phosphate, and its combination with ibuprofen.

    Evaluation of thioredoxin reductase as a novel biomarker in the diagnosis and treatment of breast cancer
    Yanran Fu, Nong Yang, Yueqin Li, Youyun Zhao, Suofu Ye, Lihui Liu, Huihui Zeng
    2014, 23(10):  711-715.  DOI: 10.5246/jcps.2014.10.090
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    Overexpression of thioredoxin reductase has been identified in a variety of primary tumors, suggesting the levels of TrxR activity between tumor patients and normal people are potentially different. Here, we performed a study to investigate the differences of TrxR activity between normal people and breast tumor patients, with the expectation that TrxR activity can be considered as a novel biomarker involved in breast cancer diagnosis and treatment. In this study, we have demonstrated for the first time that TrxR levels in breast cancer patients before therapy were significantly higher than those of normal people (P<0.05). No significant difference of TrxR activity was found among the patients at different stages of breast tumor progression. In the patient group of TrxR <10 U/mL, evaluation of TrxR activity has shown a high consistency with the results from cancer diagnostic imaging. Overall, these observations suggest TrxR as an effective biomarker to monitor and evaluate the clinical outcome of breast cancer therapeutics, and identify TrxR activity as a novel approach for breast cancer early-stage detection.

    Efficacy and safety of homoharringtonine during consolidation therapy in chronic myeloid leukemia: a meta-analysis
    Huaiping Tian, Ping Yang, Rong Tao, Jinlian Zhang, Jian Zhang
    2014, 23(10):  716-722.  DOI: 10.5246/jcps.2014.10.091
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    本文旨在系统评价高三尖杉酯碱巩固治疗慢性粒细胞白血病的疗效和安全性。通过计算机检索PubMedThe Cochrane LibraryEMbaseVIPWanFang DataCBMCNKI 数据库, 检索时限均为从建库至20145, 收集高三尖杉酯碱治疗慢性粒细胞白血病的随机对照试验。由两位研究者按照纳入与排除标准, 独立进行文献筛选、资料提取和评价纳入研究的方法学质量。采用RevMan 5.2软件进行Meta分析。结果共纳入5项研究, 423例患者。Meta分析结果显: 高三尖杉酯碱组的完全血液学反应率、主要细胞遗传学反应率和部分细胞遗传学反应率高于羟基脲组, 完全细胞遗传学反应率和轻微细胞遗传学反应率均高于羟基脲组。高三尖杉酯碱组急变率低于羟基脲组, 4年预期生存率高于羟基脲组。高三尖杉酯碱的药物不良反应较轻。结果提示, 单用高三尖杉酯碱巩固治疗慢性粒细胞白血病具有较好的短期和远期疗效, 可作为部分患者的一个治疗选择。鉴于纳入研究的方法学质量存在中度选择性偏倚的可能性, 有待开展更多高质量大样本的随机双盲临床对照试验来验证。

    Chemical constituents from the roots of Polygala wattersii Hance
    Yuhong Zhou, Qiang Guo, Yong Jiang, Pengfei Tu
    2014, 23(10):  723-730.  DOI: 10.5246/jcps.2014.10.092
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    To investigate the chemical constituents of the roots of Polygala wattersiiHance,the separation and purification were performed by solvent extraction and repeated column chromatography (CC) on silica gel, Sephadex LH-20 and macroporous resin D101, preparative TLC and semi-preparative HPLC. The structures were identified by spectroscopic analysis and comparison of their1H and 13C NMR data with those reported in literatures. Twenty-three known compounds, including eleven xanthones (1-11), nine sugar esters (1220), two triterpenoid saponins (21 and 22) and one phenylpropanoid (23) were isolated and their structures were identified as 1,3-dihydroxyxanthone (1), 1-hydroxy-3-methoxyxanthone (2), 1,3-dihydroxy-2-methoxyxanthone (3), 1,3,7-trihydroxy-2-methoxyxanthone (4), 1,3,6-trihydroxy-2,7-dimethoxyxanthone (5), 1,6,7-trihydroxy-2,3-dimethoxyxanthone (6), 1,7-dihydroxy-2,3-methylenedioxyxanthone (7), 1,7-dimethoxyxanthone (8), 1,2,3-trimethoxyxanthone (9), 1-methoxy-2,3-methylenedioxyxanthone (10), 6-hydroxy-1-methoxy-2,3-methylenedioxyxanthone (11), 3'-O-feruloyl-6-O-acetyl sucrose (12), arillatose B (13), sibricose A5 (14), sibricose A6 (15), 3',6-di-O-sinapoyl sucrose (16), tenufoliside A (17), 3'-O-3,4,5-trimethoxycinnamoyl-6-O-p-methoxybenzoyl sucrose (18), glomeratose A (19), 1-O-p-coumaroyl-D-glucopyranose (20), bayogenin-3-O-glucoside (21), tenufolin (22), and sinapic acid (23). Among them, compounds 2 and 12 were obtained from genus Polygala for the first time, and except compound 16, all others were isolated from this species for the first time.

    Recent advance in SNP identifying methods and individualized medication
    Rui Peng, Hong Zhang, Ying Zhang
    2014, 23(10):  731-738.  DOI: 10.5246/jcps.2014.10.093
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    Polymorphisms associated with genes coding for a variety of drug-metabolizing enzymes (DMEs) and associated transport proteins can influence the drug metabolism rate of individuals, potentially affecting the efficacy of drug and the occurrence of adverse reactions. Single nucleotide polymorphisms (SNPs) are prevalent in all types of genetic variations. Reliable SNP genotypingprovides excellent markers for detecting genetic polymorphisms, genetic disorders, and resistance of pathogen to drug, which are needed for the genetic diagnosis of disease and subtle genetic factors. With a large number of SNP genotyping studies being conducted, a lot of novel SNP identifying methods have been developed. Several SNP genotyping methods and techniques have been introduced for clinical test. These include TaqMan® drug metabolism genotyping assays, pH-sensing semiconductor system, high-resolution melting curve analysis (HRM) of polymerase chain reaction (PCR) amplicons, novel multiplexed electrochemical biosensor with non-fouling surface, DNA hybridization detection using less than 10-nm gap silicon nanogap structure, tetra-primer ARMS-PCR method, acoustic detection of DNA conformation in genetic assays combined with PCR, microbeads-mass spectrometry (MEMS)-based approach, and liquid chromatography-electrospray ionization mass spectrometry. Personalized medicine has changed the conventional ways of using drugs according to experiences. It focuses on making the individualized pattern for each individual based on their own characteristics. Lots of researchers are using the analysis of clinical samples to explain the relationship between the drug adverse reactions and genetic polymorphisms. But it takes a long time from collecting the blood samples for DNA extraction and genotyping to getting results on the side effect of drug through clinical study. Therefore, it is desirable to develop improved in vitro methods to study the drug metabolizing-enzymes and transport protein genetic polymorphisms.