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

  • 2013 Volume 44 Issue 3
    Published: 10 March 2013
      

  • Select all
    |
  • QI Jinlong1, ZHANG Chao1, WU Yin2, LIU Baoxia1, ZHANG Hailin1*
    2013, 44(3): 223-225.
    Abstract ( )   Knowledge map   Save
    Retigabine, an anti-epileptic agent, was synthesized from 4-nitroaniline by acylation, reduction of nitro group, protection of amino group, nitration, deprotection of amino group, and then condensation with 4-fluorobenzaldehyde to give ethyl N-[4-[(4-fluorobenzylidene)amino]-2-nitrophenyl]carbamate, followed by Pd/Ccatalyzed reduction of both nitro group and Schiff's base simultaneously with an overall yield about 44%.
  • SONG Zhenfeng, DIAO Wenrui*
    2013, 44(3): 226-227.
    Abstract ( )   Knowledge map   Save
    With absolute ethanol as the solvent, ethyl 4-chloro-n-butanoate and glycinamide hydrochloride were refluxed for 20 h in the presence of sodium bicarbonate to obtain central stimulant piracetam. After recrystallization from isopropanol, the yield was about 58% with a purity of 99.6%.
  • WANG Jianta1, WANG Yan2, DU Zhennan1, TANG Lei1*
    2013, 44(3): 227-229.
    Abstract ( )   Knowledge map   Save
    Flupenthixol dihydrochloride was synthesized from 2-trifluoromethylthioxanthen-9-one and allyl bromide by Barbier reaction, dehydration, and then condensation with N-(2-hydroxyethyl)piperazine in the presence of DBU to give flupenthixol free base, which was subjected to salt formation with an overall yield of about 47%.
  • WANG Dongmei1, DENG Yanli2, WU Song1*
    2013, 44(3): 230-233.
    Abstract ( )   Knowledge map   Save
    To perform the quality control of mirtazapine, two related substances recorded in USP34-NF29, (14bRS)-2-methyl-3,4,10,14b-tetrahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepin-1(2H)-one(C) and (14bRS)-1,2,3,4,10,14b-hexahydropyrazino[2,1-a]pyrido[2,3-c][2]benzazepin (D) were prepared, and their structures were confirmed by 1H NMR, 13C NMR and HR-MS.
  • LI Xianzhe1, ZONG Qianshou2,3, WU Jianyi2,3*, CHE Daqing4
    2013, 44(3): 233-234.
    Abstract ( )   Knowledge map   Save
    2-(3-Hydroxy-1-adamantane)-2-oxoacetic acid, the intermediate of saxaglipitin for type 2 diabetes, was synthesized from adamantyl methyl ketone(2) via two-step oxidation by potassium permanganate with an overall yield of about 74.7%: ①the molecular ratio of potassium permanganate and 2 was 2.05∶1, the temperature was controlled at 50 - 55 ℃ with tetrabutylammonium bromide as catalyst, and the pH value was adjusted to 12 - 13; ②additional 1.2 eq potassium permanganate was added, the temperature was controlled at 40 - 45 ℃ and the pH value was adjusted to 8 - 9.
  • YANG Li, LUAN Hansen, XU Fenglan, WANG Hao
    2013, 44(3): 235-237.
    Abstract ( )   Knowledge map   Save
    The residual tin in poly(lactic-co-glycolic acid) (PLGA) after purification by dilute acid solution or organic solvent extraction was determined to compare the removal efficiency of the two methods. The influences in the organic solvent extraction process on the residual tin were investigated. The results showed that the residual tin was less than 10 μg/g when the 1% PLGA acetonitrile solution was extracted with the equal volume of petroleum ether for three times. This method without inorganic acid could avoid the degradation of PLGA.
  • GUO Chaojiang, ZHANG Lan, WANG Cheng, WANG Zhaona, XU Wencheng
    2013, 44(3): 238-241.
    Abstract ( )   Knowledge map   Save
    The influence of decanoic acid sustained-release particles on daptomycin fermentation process of Streptomyces roseosporus NTF206 was investigated. The optimum formulation of decanoic acid sustained-release particles was obtained by orthogonal design, which was decanoic acid 10%, stearic acid 1.0%, polyethylene glycol 1.5%and agar 1.2%, and the feeding conditions of the particles were further optimized. The results showed that the optimized conditions for daptomycin production were first feeding time of 36 h, decanoic acid of 4.8 ml/L per time and at the interval of 36 h. The yield of daptomycin was 121.8 mg/L which was 79% higher than the control, and adding times of decanoic acid was 50% fewer than the control.
  • HU Jin1, GUO Hong2, WANG Chenggang2, WANG Xinglin2*
    2013, 44(3): 249-253.
    Abstract ( )   Knowledge map   Save
    The hydrophilic matrix tablets with SWELSTARTM MX-1 (hereinafter referred to as MX-1) or hydroxypropyl methylcellulose (HPMC) as matrix were respectively prepared with water-soluble propranolol hydrochloride as the model drug. The swelling and erosion tests of the two kinds of blank matrix tablets were carried out in 0.1 mol/L HCl, pH 6.8 and pH 7.2 phosphate buffer (PBS) and water. The results showed that the changes in pH value and ionic strength of the medium had no significant influence on the swelling and erosion behaviors of MX-1, but affected HPMC a lot. The zero-order, first-order, Higuchi and Ritger-Peppas models were adopted to fit the release data of the two kinds of drug-loaded matrix tablets in above media. The HPMC tablets in pH 7.2 PBS released faster than in
    the other three media. While the release behaviors of MX-1 matrix tablets in four media had no significant difference. All the release data in four media showed a good ?t into the Ritger-Peppas equation, the drug release mechanism of the two matrix tablets were the combined effect of drug diffusion and polymeric erosion. Compared with HPMC, MX-1 had a better resistance to high ionic strength capability.
  • LIU Qiong, WANG Juan, CHEN Xiuhua*
    2013, 44(3): 253-257.
    Abstract ( )   Knowledge map   Save
    The Fe3O4 magnetic nanoparticles decorated graphene oxide (GO) composites were in situ synthesized by co-precipitation method with the GO sheets prepared by improved Hummers method. The properties of the composites were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The results showed that the mean particle size of the Fe3O4 nanoparticles in the composites was 30 nm, and some aggregates were 50 - 100 nm. Some functional groups of GO in the composites could be used as the sites binding with the drugs. The composites could also load drugs by π-π conjugation. In the presence of external magnetic field, the prepared composites rapidly gathered near the permanent magnet. The results of in vitro cytotoxicity test showed that in the concentration range of 0.5 - 5 000 μg/ml, the composites had no obvious cytotoxicity on lung cancer cells A549 and breast cancer cells ZR-75-30.
  • SHI Haoqiang1, YANG Jun2*, ZHANG Liqun1, LU Huilan2, CHEN Bing1
    2013, 44(3): 258-264.
    Abstract ( )   Knowledge map   Save
    The steady state trough concentration (c0) of sirolimus (1) and pathophysiological data of 60 Chinese renal transplantation patients were enrolled retrospectively. The CYP3A5*3 genotype of each patient was determined. The nonlinear mixed effect model (NONMEM) software was adopted to establish the population pharmacokinetic (PPK) model for 1 in Chinese renal transplantation patients. The influences of age, gender, body weight, renal and liver function and CYP3A5*3 genotype on PPK parameters were quantitatively investigated. Bootstrap method was used for the validation of final model. Total 486 c0 data of 1 were obtained from 60 patients with different stages. The average value of c0 was (7.1±3.4)ng/ml. There were 3, 22 and 35 patients with CYP3A5 *1/*1, *1/*3 and *3/*3 genotype. The results showed that a one-compartment model was the most suitable model for Chinese renal transplantation patients.
    The clearance (CL/F), volume of distribution (Vd/F) and absorption rate constant (Ka) were (13.1±0.78)L/h, (755±38.2)L and 2.20 h-1, respectively. The body weight, total bilirubin (TBIL) and CYP3A5*3 genotype were found to have significant influences on clearance of 1 (P<0.01).
  • SUN Jian1, XU Hongjiang1, ZHU Yuhui2, WU Yong2*
    2013, 44(3): 265-268.
    Abstract ( )   Knowledge map   Save
    Reduced glutathione was oxidized by hydrogen peroxide to obtain oxidized glutathione. The optimal process was as follows: the reduced glutathione in 200 - 300 g/L was reacted with 3% hydrogen peroxide at the pH value of 5.0 - 6.0. The purity and total yield of oxidized glutathione after purification were 99.5% and 95.9%, respectively. Furthermore, the therapeutic effect of oxidized glutathione on acute liver injury in mice induced by paracetamol was investigated. The results showed that it could significantly decrease the activities of glutamate pyruvate transaminase and glutamic-oxal(o)acetic transaminase, and there was no significant difference between oxidized glutathione and the reduced form.
  • ZHOU Changhui1, WANG Qingli2, WANG Zheng1, ZHANG Ming1, CHANG Yan1*
    2013, 44(3): 269-273.
    Abstract ( )   Knowledge map   Save
    A study was performed to validate the three-color ?ow cytometry-based technique (FCM) for
    enumerating micronucleus (MN) in mouse peripheral blood and to evaluate the degree of correspondence between FCM and conventional microscopy-based method. For these studies, groups of ten mice received a single dose of solvent (normal saline or 0.5% CMC-Na), benzo[a]pyrene, ?uorouracil, methotrexate, mitomycin C, methyl methanesulfonate, colchicine, vincristine sulfate, new compound A or new compound B. Micronucleated reticulocyte frequencies were measured by FCM [20 000 reticulocytes (RET) per sample] while micronucleated polychromatic erythrocytes were scored by conventional microscopy-based analysis [2 000 polychromatic erythrocytes (PCE) per sample]. Parallel analysis of micronucleus induction in peripheral blood by FCM and bone marrow using conventional microscopybased method showed concordant results (r=0.913). The ?ow cytometric assessment of MN-RETs in mouse peripheral blood was a sensitive, fast and objective automatic analysis of micronuclei, which could be an acceptable alternative to microscopy-based analysis in mouse bone marrow micronucleus test in vivo.
  • SUN Shuaiting, JIN Yi, YUAN Bo, JIANG Xuan, XU Haiyan*
    2013, 44(3): 274-280.
    Abstract ( )   Knowledge map   Save
    Triptolide and celastrol mixture was administrated to rats by gavage. A LC-MS/MS method under negative ion model with full scan method was developed and applied to characterize the metabolites in serum, urine and feces. The prototype drugs were only detected in rat serum. Three triptolide metabolites in urine were found, which were inferred as mono-hydroxyl metabolite, epoxide-hydrolyzed metabolite and GSH conjugate. The only component in feces was found, which was inferred as another mono-hydroxyl metabolite. It was found one celastrol metabolite in urine, which was inferred as the glucuronide. The component found in feces as celastrol metabolite was the sulfate.
  • TANG Boya1, YANG Yifang1*, HUANG Chunyue1, LUO Zeyuan2, LI Cunyong2
    2013, 44(3): 281-285.
    Abstract ( )   Knowledge map   Save
    The HPLC fingerprint spectra was established for discrimination of spurious breeds of Radix Pulsatillae. The analysis was performed on a XB-C18 column with the mobile phase of acetonitrile-0.1% phosphoric acid by gradient elution at the detection wavelength of 210 nm. The analytical method of HPLC fingerprint was established and the common pattern of fingerprint contained 29 co-possessing peaks. The fingerprint data was processed by the method of similarity and clustering analysis. The fingerprint differences between Radix Pulsatillae and its spurious breeds were so obvious that they would be distinguished with each other by clustering analysis. The HPLC fingerprint of Radix Pulsatillae with high specificity could be used to control its quality .
  • BAI Ruixia
    2013, 44(3): 286-289.
    Abstract ( )   Knowledge map   Save
    An HPLC method with cellulose tris(3,5-dimethylphenylcarbamate) as chiral stationary phase (Chiralpak IB) was established for the chiral separation of racecadotril enantiomers. The influences of the mobile phase composition, column temperature and flow rate on the resolution were investigated. A complete resolution was achieved under the following conditions: hexane-isopropanol (60︰40) as the mobile phase at the flow rate of 0.6 ml/min, column temperature of 25 ℃ and detection wavelength of 210 nm. The calibration curves of cadotril enantiomers were linear in the concentration range of 0.01 - 0.5 mg/ml. The average recoveries were 99.7% and 99.6%, with RSDs of 0.79% and 0.91%, respectively.
  • CHEN Zhongya, ZHAO Yan, TAO Tao*
    2013, 44(3): 290-295.
    Abstract ( )   Knowledge map   Save
    RGD peptides are small peptides containing arginine-glycine-aspartic acid triple peptide motif and can bind specifically to integrin receptors on cell surface. Integrin receptors, especially αvβ3, are highly expressed on tumor cell (glioma for example) surface while showing low expression on mature endothelial cells. Therefore, in the studies of targeted therapy and imaging for glioma, the competitive binding between ectogenic RGD peptides and integrin receptors on the tumor cell surface has been widely studied. In this paper, the typical methods and progress in RGD peptide-mediated targeted therapy and imaging for glioma in recent years are reviewed.
  • SUN Feng'e, FANG Hao*
    2013, 44(3): 296-302.
    Abstract ( )   Knowledge map   Save
    Apoptosis is closely related to the occurrence of many human diseases. Excessive apoptosis causes neurodegenerative diseases, while insufficient apoptosis is related to the generation of cancers and other diseases. Nowadays, Bcl-2 family proteins are found to be important in apoptosis regulation and many inhibitors of Bcl-2 have been investigated. Recently, more and more researchers focus on the studies of Mcl-1, which is a member of Bcl-2 family proteins, due to its unique role in the apoptosis pathway. This paper summarizes the structure and function of Mcl-1, and the recent progress of Mcl-1 protein inhibitors as potential antitumor agents.
  • RUXIANGULI Yiming1,2, HE Jiang2, LIU Chong2, YANG Weijun2*
    2013, 44(3): 310-313.
    Abstract ( )   Knowledge map   Save
  • WU Linping
    2013, 44(3): 314-317.
    Abstract ( )   Knowledge map   Save