主办:上海医药工业研究院
   中国药学会
   中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA

Archive

  • 2015 Volume 46 Issue 07
    Published: 10 July 2015
      

  • Select all
    |
  • ZHANG Lijuan1, LI Chao3, YANG Jiao2, SONG Tiebing2, ZHANG Xiaoyou2*
    Abstract ( )   Knowledge map   Save
    Ozagrel, an antithrombotic drug, was synthesized from 4-bromotoluene by bromination and N-alkylation to give 1-(4-bromobenzyl)-1H-imidazole which was subjected to Heck coupling reaction with methyl acrylate in the presence of α-HPCD and hydrolysis with an overall yield of 58%.
  • KONG Hao1, GENG Haiming2, MEI Yudan1, ZHU Xiaoqi1, SUN Pinghua1*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Bilastine was prepared from methyl α,α-dimethylphenylacetate (2) via Friedel-Crafts acylation and reduction to give methyl α,α-dimethyl-4-(2-bromoethyl)phenylacetate, which was subjected to nucleophilic substitution with 2-(piperidin-4-yl)-1H-benzimidazole and 2-chloroethyl ether followed by hydrolysis with an overall yield about 54%(based on compound 2).
  • HUANG Kun, JIANG Hailong, WU Yulan, CHU Qingsong*
    Abstract ( )   Knowledge map   Save
    Dapagliflozin was synthesized from 5-iodo-2-chloro-4'-ethoxyldiphenylmethane via condensation with 2,3,4,6-tetra-O-trimethylsilyl-D-glucono-1,5-lactone, methyl etherification and deprotection to give 2-chloro-5-(1- methoxy-D-glucopyranose-1-yl)-4'-ethoxyldiphenylmethane which was subjected to reduction with Et3SiH-BF3·Et2O to afford crude dapagliflozin, followed by etherification with acetyl chloride and hydrolysis with an overall yield of 40% and a purity of 99.9%.
  • WU Liqian1, QIU Pengcheng1, JIANG Min2, JIAO Huirong1, ZHANG Fuli1*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    To perform the quality control of regadenoson, three related substances were prepared and their structures were confirmed by MS, 1H NMR and 13C NMR. These substances were 2-(4-carboxyl-1H-pyrazol-1- yl)adenosine (A), 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]-N6-methyladenosine (B), and [1-(6-amino-9Hpurin- 2-yl)-1H-pyrazole-4-yl]-N-methylcarboxamide(C).
  • GUO Qiuxiang, WU Yuanjie, CHEN Shaoxin*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A Yarrowia lipolytic SIPI-N-5 strain, which could produce eicosapentaenoic acid (EPA), was used as the starting strain. After optimization of carbon and nitrogen sources, the titer of EPA was 1 324 mg/L in fermentation medium consisting of 5% glycerol and 0.5% yeast extract in flask shake culture. Furthermore, fed-batch culture of SIPI-N-5 was conducted in a 5 L fermentor. The yield of EPA was increased to 2 701 mg/L in an appropriate medium by feeding glucose and yeast extract during the fermentation process. The fermentation product was extracted and EPA equivalent to 33.9% of total lipids was obtained.
  • HU Qing, SUN Jian, ZHANG Su, FENG Rui, JI Shen*
    Abstract ( )   Knowledge map   Save
    A TLC method was established for the simultaneous qualitative analysis of 48 banned pigments in traditional Chinese medicine. Sample powders were extracted by ultrasonication with acetonitrile, 0.1% formic methanol solution and methanol∶0.1% formic acid (3∶2), respectively. The acetonitrile extraction and the liposoluble pigments reference solution were applied to a silica gel plate separately and developed with petroleum ether∶diethyl ether∶ formic acid (80∶20∶1). The 0.1% formic methanol solution extraction and the basic pigments reference solution were developed with ethyl acetate∶ethanol∶water∶amonia (12∶1∶1∶1.2), and the methanol∶0.1% formic acid (3∶ 2) extraction and the acid pigments reference solution were developed with ethyl acetate∶ethanol∶water∶amonia (6∶ 4∶2∶0.2). The plates were observed under daylight. The limits of detection of 48 banned pigments were 0.025 - 0.6 μg. This method, with simple pretreatment and rapid analysis, was suitable for the simultaneous scan of pigments in traditional Chinese medicine.
  • LIU Ying1,2, CUI Xiuming1,2, YANG Ye1,2, YANG Xiaoyan1,2, QU Yuan1,2*
    Abstract ( )   Knowledge map   Save
    An HPLC method was established for the determination of ginsenosides Rb1, Rc, Rb2 and Rb3 in the stems and leaves of Panax notoginseng. The qualities of stems and leaves of Panax notoginseng from different origins were evaluated. A C18 column was used, with the mobile phase of acetonitrile∶water by gradient elution, at the detection wavelength of 203 nm. It was linear for ginsenosides Rb1, Rc, Rb2 and Rb3 in the range of 0.002 - 1.0 mg/ml. Their recoveries were 96.0%, 105.3%, 103.7% and 96.1%, with RSDs of 1.32%, 2.98%, 0.95% and 2.11%, respectively.
  • WANG Dejian, ZHANG Hui, YAO Peijun, WANG Ling, CHEN Jun*
    Abstract ( )   Knowledge map   Save
    Four kinds of active targeting liposomes loaded with coumarin-6 surface modified with NGR (Asn-Gly-Arg) were prepared with distearoyl phosphatidylcholine (DSPC), hydrogenated soya phosphatide (HSPC), dipalmitoyl phosphatidylcholine (DPPC) and dimyristoyl phosphatidyl choline (DMPC) as carrier, respectively. The results showed that the mean diameters of these four liposomes were in the range of 120 - 160 nm, and they all had a uniform size distribution and nearly neutral potential. Their encapsulation efficiencies were all above 95%. According to the result of differential scanning calorimetry (DSC) analysis, the phase transition temperature (Tm) values of these liposomes were ranked in descending order as follows: DSPC liposomes, HSPC liposomes, DPPC liposomes and DMPC liposomes. With CD13 overexpressing cells HT1080 as the cell model, flow cytometry analysis and confocal laser
    microscopy were applied to evaluate the cellular uptake efficiency. The results showed that the cellular uptake efficiencies of the NGR-modified liposomes were positively correlated with their Tm values.
  • DU Jiefeng1, YE Qinghua1, LIU Junfeng2, PENG Yourui2, YANG Peiming1*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    With the yield of inclusion complex and the utilization ratio of volatile oil as the indexes, an orthogonal design was adopted to optimize the process conditions for the preparation of β-cyclodextrin (β-CD) inclusion complex of the mixed volatile oils from Flos Magnoliae, Wild Chrysanthemum, Herba Schizonepetae and Asarum by applying saturated water solution method. The formation of inclusion complex was preliminary proved by the results of DSC and XRPD analyses. A GC method was used to detect the content changes of several compositions in mixed volatile oils before and after inclusion. The stability of β-CD inclusion was also investigated. In conclusion, the optimum inclusion process conditions were as follows: the proportion of volatile oil to β-CD was 1∶8, inclusion process was carried out at 60 ℃ for 90 min. The compositions of volatile oil were not changed after inclusion. The results of stress testing as well as accelerated and long-term tests showed that the product was rather stable.
  • MAO Jingyi1, ZHANG Juanjuan2, MUYASSAR·Mamtili1, LI Fulun1, LI Bin1*
    Abstract ( )   Knowledge map   Save
    An o/w type cream loaded with the extract of Cortex Phellodendri obtained by reflux method was prepared. The concentration of berberine hydrochloride (1) was determined by HPLC method. The in vitro permeation characteristics through excised nude mouse skin were investigated by modified Franz diffusion cells. The effects of microneedle-roller on the percutaneous penetration of 1 from the cream and the retention amount of 1 in skin were discussed. The results showed that the cumulative permeation amounts at 12 h in the groups without or with microneedleroller skin treatment were (0.161±0.008) and (0.978±0.034)mg/cm2, the percutaneous penetration rates were (0.035± 0.007) and (0.197±0.018)mg·cm-2·h-1, while the retention amounts of 1 in the two groups were (0.373±0.021) and (1.364±0.342)mg/cm2. It indicated that microneedle-roller could significantly increase the percutaneous penetration amount of 1 and its retention amount in skin (P<0.05).
  • XIE Jiangchuan, HE Dan, YAN Zijun, ZHOU Yunli, ZHANG Jingqing*
    Abstract ( )   Knowledge map   Save
    Asparaginase(1)-loaded self-assembled nanoparticles (THDCD) with polyethylene glycol (PEG) grafted hyaluronic acid and dimethyl-β-cyclodextrin were prepared. The in vitro activity and stability of the product and free 1 were investigated and compared. The optimum temperature and optimum pH value for THDCD and 1 were determined and their acidic and basic stability, thermal stability, storage stability, plasma stability, resistance to trypsin and resistance to several metal ions and organic compounds were compared. The optimum temperature and optimum pH value for THDCD were 50 ℃ and pH 6.5, while for 1 were 60 ℃ and pH 7.5. The above stabilities and resistance abilities of THDCD were all superior to 1. The results showed that THDCD not only improved the activity but also significantly enhanced the stability of 1 in vitro.
  • CUI Wenning1,2, WANG Shumei1*, YANG Xiuling1, ZHANG Zhiqing1, WANG Lina1
    Abstract ( )   Knowledge map   Save
    An LC-MS/MS method was established for the determination of rivaroxaban(1) in rat plasma. A C18 column was used, with the mobile phase of acetontrile∶10 mmol/L ammonium acetate solution(adjusted to pH 3.14 by formic acid)(50∶50)and imrecoxib(2) as the internal standard. An ESI source was applied and operated in positive ion multiple-reaction monitoring mode. The detected ions were m/z 436.2→m/z 145.2(1)and m/z 370.1→m/z 278.0(2). The
    main pharmacokinetic parameters of 1 in SD rats after ig administration of rivaroxaban were as follows: cmax(438.19± 122.02)ng/ml, tmax (0.69±0.20)h, AUC0→24 h(1 692.75±654.72)ng·h·ml-1, AUC0→∞(1 760.25±649.11)ng·h·ml-1, t1/2(3.46± 1.10)h.
  • ZHANG Rui1, WANG Yu2, ZHANG Shaofeng1, ZHANG Haiyan1, YANG Ming1
    Abstract ( )   Knowledge map   Save
    In vitro hemolysis test was conducted to determine the hemolysis caused by eight types of chemical compositions of Tween-80. The results showed that there were significant differences among the hemolysis of the eight compositions. No hemolysis was observed in polyoxyethylene sorbitan (PS), polyoxyethylene isosorbide (PI) or polyoxyethylene isosorbide dioleates (PID) at 500 μg/ml. Polyoxyethylene sorbitan trioleates (PSTri) at 300 μg/ml and
    polyoxyethylene sorbitan tetraoleates (PSTetra) at 500 μg/ml could cause hemolysis, while polyoxyethylene sorbitan monooleate (PSM) at 80 μg/ml, polyoxyethylene sorbitan dioleates (PSD) at 120 μg/ml and polyoxyethylene isosorbide monooleate (PIM) at 30 μg/ml showed hemolytic effect. It was suggested that the contents of chemical compositions of commercially available Tween-80 should be controlled in order to reduce the hemolytic toxicity.
  • CHEN Pengcheng1,3, HOU Jingyu1,3, HU Jie2,3, GONG Zipeng1,3, WANG Yonglin1,3*
    Abstract ( )   Knowledge map   Save
    The absorption kinetic characteristics of the main active components in extract of Cortex Eucommiae, including geniposidic acid (1), neochlorogenic acid (2), chlorogenic acid (3) and cryptochlorogenic acid (4) in rats' intestine, were investigated by adopting the in situ rat circulation intestinal perfusion model. A UPLC-MS/MS method was established for the determination of 1 - 4, and their absorption at different conditions, including pH values, sample concentrations, bile and P-gp inhibitors was investigated. As a result, the absorption of 1 was poor at pH 7.4, while that of 2 and 4 was significantly different at different pH values. But 3 was insensitive to pH values. The accumulated absorption rates (3 h, A) of 2 and 3 at middle concentrations (4.0 mg/ml) were higher than that at high concentrations (8.0 mg/ml). There was saturation phenomenon of absorption when they were at high concentrations. The bile significantly inhibited the absorption of 1 - 4. However, P-gp inhibitor had no effect on the absorption of the Cortex Eucommiae extract. The results indicated that the absorption of 1 - 4 existed in the whole intestinal segments, while the main absorption site was at the small intestine. It also suggested that 1 - 4 might not be the substrates of P-gp.
  • YANG Liuliu, CHEN Fang*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An HPLC method was established for the determination of asenapine maleate sublingual films. A C18 column was used, with the mobile phase of 1.0% triethylamine solution (adjusted to pH 6.8 with phosphoric acid)∶ acetonitrile (46∶54), at the detection wavelength of 274 nm. It was linear for asenapine in the concentration range of 20 - 80 μg/ml. The average recovery was 99.8%, with RSD of 0.5%.
  • ZHANG Jialin, PENG Xingsheng, WANG Linbo*, REN Feiliang, CHEN Guiliang
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The method for the content determination of potassium, calcium, sodium and magnesium in the current Ensure registration standard was improved. Samples were digested with nitric acid∶perchloric acid (1∶1) under water bath at 60 ℃ for 3 hours, and it was determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) method. It was linear in the range of 0 - 30 μg/ml for potassium, calcium and sodium, and in the range of 0 - 5 μg/ml for magnesium. Their recoveries were (103.0±1.1)%, (101.3±0.9)%, (100.8±0.6)%, and (97.4±0.8)%, respectively.
  • ZHU Di1, XIANG Wenying2, WANG Aimin1,3, LAN Yanyu1,3, ZHENG Lin2,3*
    Abstract ( )   Knowledge map   Save
    An ion chromatography method was established for the determination of the anions of organic and inorganic acids in Shenxiong glucose injection, including lactic acid, acetic anion, formic anion, chloride, nitric anion, sulfuric anion and succinic acid. An Ion Pac AS11-HC anion exchange column was used, with the eluent of potassium hydroxide solution for gradient elution. An ASRS 300 type suppressor was applied in the cycle suppression mode and with the current of 50 mA. It was linear for succinic acid in the range of 0.25 - 5 μg/ml, for the others in 0.5 - 10 μg/ml. Their recoveries were 103.6%, 104.4%, 100.1%, 101.5%, 98.8%, 99.1% and 102.4%, with RSDs of 2.9%, 1.1%, 0.5%, 2.8%, 2.9%, 3.1% and 8.3%, respectively.
  • LU Huijuan, JIA Canchao, ZHAO Hongning, BIAN Jiang, JI Shengguo*
    Abstract ( )   Knowledge map   Save
    A near-infrared (NIR) spectroscpoy method was established for the determination of moisture in Prunella vulgaris L.. The NIR spectra of P. vulgaris were collected by NIR diffuse reflectance spectroscopy technique. A quantitative model of moisture was established by partial least squares (PLS) with oven drying method as the reference value. It was verified by the unknown samples. The correlation coefficients (R2), root-mean-square error of calibration (RMSEC) and root-mean-square error of cross-validation (RMSEP) of the quantitative calibration model of moisture were 0.9882, 0.129 and 0.134, respectively. The   difference between NIR prediction values and the reference values of the validation set was not significant.
  • LIANG Min, DU Yanling, LI Chunlei
    Abstract ( )   Knowledge map   Save
    An HPLC-RID method was established for the determination of 1-palmitoyl-sn-glycero-3- phosphocholine(MPPC), 1-stearoyl-sn-glycero-3-phosphocholine(MSPC), palmitic acid(PA) and stearic acid(SA) in pegylated liposomes. A Symmetry C18 column was used, with the mobile phase of methanol∶THF∶ammonium acetate solution (0.15 mol/L) ∶glacial acetic acid (79∶6∶11∶4). The calibration curves were linear in the ranges of 0.04 - 0.30 mg/ml for MPPC and MSPC, and 0.02 - 0.15 mg/ml for PA and SA. Their average recoveries were 101.5%, 101.4%, 101.4% and 99.1%, respectively, with RSDs no more than 2.0%.
  • DING Yang, WANG Ruoning, HAN Yue, ZHANG Xu, ZHOU Jianping*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Blood brain barrier (BBB) is a major obstacle for the treatment of various central nervous system (CNS) diseases. With the development of nanotechnology, great progress has been made in the field of novel braintargeting drug delivery system. By taking advantages of multiple BBB penetration mechanisms, including receptor-, carrier- and adsorptive-mediated transcytosis and transient BBB opening, nanocarriers can deliver drugs across BBB and accumulate in brain to achieve desired therapeutic effects for CNS diseases. Recent advances in nano-scale drug delivery systems across BBB and their mechanisms are summarized in this paper.
  • GAO Tianying, WANG Yonglu, LI Xueming*
    Abstract ( )   Knowledge map   Save
    The unique biopharmaceutical characteristics of drug nanocrystals showed in the progress of in vivo absorption and distribution have attracted wide attentions of researchers. This paper reviews the absorption characteristics of drug nanocrystals in the human bodies, the effects of administration routes and the applications to targeted delivery researches. It is useful to understand the biopharmaceutical characteristics of drug nanocrystals more deeply and to guide the development of the formulation of drug nanocrystals.
  • XU Bin1, MA Donglei2, LIU Zhong2*
    Abstract ( )   Knowledge map   Save
    There are many natural bitter compounds. Most of them lead to bitterness through the activation of bitter taste receptor. Bitter taste receptor inhibitors play important roles in food and drug taste masking by interacting with bitter taste receptors. This review summarizes the inhibitors of bitter taste receptors and the applications in pharmaceuticals.
  • GU Shuangxi1, XUE Ping1, ZHU Yuanyuan2, JU Xiulian1
    Abstract ( )   Knowledge map   Save
  • YI Xianghua, LI Qiong*, ZHU Xiuhuang
    Abstract ( )   Knowledge map   Save
  • GUO Wen
    Abstract ( )   Knowledge map   Save