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

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  • 2015 Volume 46 Issue 2
    Published: 10 February 2015
      

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  • MO Mingguang, CAO Shenghua*
    2015, 46(2): 117-119.
    Abstract ( )   Knowledge map   Save
    Lomerizine hydrochloride was prepared from bis(4-fluorophenyl)methanone(2) via reduction, chlorination with sodium chloride-concentrated sulfuric acid, reaction with piperazine to obtain the 1-[bis(4- fluorophenyl)methyl]piperazine(5), which was subjected to reductive amination with 2,3,4-trimethoxybenzaldehyde with sodium triacetoxyborohydride as reducing agent and trifluoroacetic acid as catalyst, then salt formation with the overall yield of 54% based on compound 2. The improved process was more friendly to environment.
  • ZHAO Shikui, MA Kang, GUO Qingming, WANG Zhenzhong, XIAO Wei*
    2015, 46(2): 120-122.
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    Valganciclovir hydrochloride was synthesized from ganciclovir via tritylation to protect amino and one hydroxyl to afford N,O-ditritylganciclovir, which was subjected to condensation with N-benzyloxycarbonyl-L-valine followed by detritylation, acidification, hydrogenation to debenzyloxy carbonylation and crystallization in aqueous isopropanol with an overall yield of 34%.
  • TAN Shanlun1,2, ZANG Chengxu2, DAI Li2, HUANG Jinghua3, ZHANG Dazhi1,2*
    2015, 46(2): 123-126.
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    Nitidine chloride was synthesized from 4-(benzo[d][1,3]dioxol-5-yl)-2-(3,4-dimethoxyphenyl)-4- oxobutanenitrile via hydrolysis and reduction to give 4-(benzo[1,3]dioxol-5-yl)-2-(3,4-dimethoxyphenyl)butanoic acid, subsequent Friedel-Crafts cyclization, Leuckart reaction, and cyclization to obtain 2,3-methylenedioxy-8,9-dimethoxy- 4b,10b,11,12-tetrahydrobenzo[5,6-c]phenanthridine, which was subjected to aromatization with Pd/C, followed by methylation with dimethyl sulfate and salt exchange with sodium chloride. The total yield was 2.5% in the optimized process, all the reaction conditions were mild, and the reagents were cheap and commercial available.
  • YUAN Fang, GE Han, SHEN Shunyi*
    2015, 46(2): 127-129.
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    Nine new 9-substituted acyl hydrazone clarithromycin derivatives were synthesized from clarithromycin. The antibacterial activities of the title compounds were tested in vitro and the results showed that these compounds exhibited good antibacterial activities against the tested gram-positive bacteria including Staphylococcus albus, Diplococcus lanceolatus and Enterococcus. Some of the compounds were also rather actived against Staphylococcus aureus and Gamma streptococcus.
  • PAN Ying1, TANG Lingzhi2, ZHANG Lumian1, ZHENG Jinhong1*
    2015, 46(2): 130-134.
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    Eleven unreported 1-feruloyl-4-substituted benzylpiperazine hydrochlorides were synthesized from ferulic acid, piperazine and substituted benzyl chloride. The hydroxyl radical scavenging activities were evaluated by the 1,10-phenanthroline-Fe2+ hydroxyl radical′s detection system. The results showed that all the target compounds had hydroxyl radical scavenging activities in different degrees and the preliminary structure-activity relationship was discussed.
  • ZHANG Shun1, ZHA Yufeng1, FU Xiaozhong1, DONG Yongxi1, WANG Yonglin2*
    2015, 46(2): 135-138.
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    4'-N-substituted aminomethylbenzoate-7-substituted nicotinic acid ester derivatives of scutellarein (1a - 1f) were prepared in four steps from scutellarein, N-substituted aminomethylbenzoic acid and 6-substituted nicotinic acid in the presence of N,N'-dicyclohexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP). The structures of compounds 1a - 1f were confirmed by 1H NMR, ESI-MS and HRMS. Physicochemical properties and in vitro antioxidant activities were evaluated. The results showed that incorporation of nicotinic ester group at 7-position of 4'-N-substituted aminomethylbenzoate derivatives of scutellarein could enhance in vitro antioxidant activities and aqueous solubility. Compound 1d had higher solubility, stability and antioxidant activity deserved further research.
  • SONG Bo, ZHOU Tongliang, LI Ridong*, YANG Yan
    2015, 46(2): 139-141.
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    The impurity was obtained in the work-up by methylsulfonic acid in MeOH of the Grignard reaction in the synthesis of canagliflozin. Its structure was identified as (2S,3S,4R,5R)-1-[3-[[5-(4-fluorophenyl)thiophen-2- yl]methyl]-4-methylphenyl]hexane-1,2,3,4,5,6-hexaol (A) by HRMS and two-dimensional NMR.
  • NA Ke, LIU Yongshuang, YANG Xiaojing, ZHAO Wenjie*
    2015, 46(2): 142-144.
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    An antitumor bioactive compound 1403C was separated and purified from fermentation broth produced by mangrove endophytic fungus Fusarium proliferatum. The mycelium was collected by filtration of fermentation broth and extracted three times with 75% ethanol at 70 ℃ and pH 2.0. After that, the extract was diluted to ethanol concentration of 30% by water followed by purification using Amberchrom CG161 resin column which could adsorb low-polar impurities. The refined solution was concentrated to anhydrous then crystallized with 75% ethanol at 80 ℃ to obtain red crystalloid. Six batches of 1403C preparation were performed with an average yield of 35.9%.
  • QING Weixia1,2, WANG Youyou1, WANG Yanyan1, LIU Xiuhua1,3*, ZHAO Dongbao1
    2015, 46(2): 145-148.
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    Luteolin-7-O-β-D-glucoside (1, 7.9 mg) and lonicerin (2, 5.6 mg) were isolated and prepared from crude extract of Lonicera japonica leaves(35.2 mg)by high-speed countercurrent chromatography (HSCCC) by one-step separation. The purity of compound 1 and 2 were 98.0% and 92.1%, determined by HPLC and calculated according to peak area normalization.
  • SUN Donghong, SHANG Guanghua
    2015, 46(2): 149-151.
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    The extraction process of artemisic acid (1) and dihydroartemisinic acid (2) from Artemisia annua mutterlauge was optimized. A L9(34) orthogonal design was conducted, taking the extraction yields of 1 and 2 as indexes, with ethanol extraction temperature, dosage of sodium bicarbonate solution, ethanol concentration and the concentration of sodium hydroxide solution as factors. The optimum technological parameters for 1 and 2 extraction were as follows:
    ethanol concentration of 80%, extraction temperature of 15 ℃, sodium bicarbonate solution of 20 ml, and sodium hydroxide solution concentration of 3%. The extraction yield of 1 and 2 were 31.0% and 30.5%, respectively, with the purities over 98%.
  • GONG Ya, WANG Peiqi, ZHOU Yanbin, LIANG Feng, DING Jinsong*
    2015, 46(2): 152-156.
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    An adduct of phenylephrine and maleic acid could be formed through the reaction of phenylephrine hydrochloride (1) and chlorphenamine maleate (2) in solid preparation. The influences of temperature (25 and 50 ℃), water content (0 and 10 %), pH regulators (lactic acid, citric acid, DL-tartaric acid and potassium hydrogen tartrate) and antioxidants (L-cysteine and propyl gallate) on the stability of the mixture of 1 and 2 were investigated. The results
    showed that the contents of fumaric acid and the adduct in the mixture increased with the increasing of temperature and water content, while adding potassium hydrogen tartrate and propyl gallate into the mixture could significantly decrease the contents of fumaric acid, the adduct and other impurities of 1.
  • CHENG Yubao, XIAO Yujun, WANG Zheng, LIU Junhua
    2015, 46(2): 157-161.
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    The influence factors which might cause turbidity of docetaxel injection were analyzed and investigated. The results showed that the main factor was the silica gel pipeline in workshop. Thus, stainless steel and teflon pipeline were applied to replace silica gel pipeline, then three batches of docetaxel injection were prepared for verification. The characteristics of the product stored at 2 - 8 ℃ for 12 months were not significantly changed. The results showed that the quality of these products met company requirements. It indicated that using stainless steel and teflon pipeline to substitute silica gel pipeline was a feasible method to solve the turbidity problem of docetaxel injection.
  • HE Yuan, ZHANG Yarong, LI Qiuxia, WANG Chi*
    2015, 46(2): 162-166.
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    The curcumin chitosan nanoparticles were prepared by ionotropicgelation method. Then hyaluronic acid was connected to the chitosan by covalent coupling. The hyaluronic acid modified curcumin chitosan nanoparticles were spherical, the average diameter, entrapment efficiency and drug loading of the product were (205.3±11.4)nm, 42.7% and 28.4%, respectively. The binding rate of hyaluronic acid to nanoparticles was 39%. The results of MTT test showed that the proliferation inhibition effect of the product on CD44-overexpressing A549 cells was significantly higher than that of the unmodified nanoparticles or free drug. However, the inhibitions of CD44-unexpressing HepG2 cells proliferation by modified and unmodified nanoparticles were similar.
  • ZHAO Xiaoxian1, Li Xin2, WANG Juyue2, ZHAO Kai2,3*, ZHANG Le2
    2015, 46(2): 167-171.
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    The inclusion complexes of sulfobutyl ether β-cyclodextrin (SBE-β-CD) with lansoprazole were prepared by freeze-drying method. The formation of inclusion complexes were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and thin layer chromatography (TLC). The results showed that there were interactions between lansoprazole and SBE-β-CD. The results of phase solubility test showed that the apparent solubility of lansoprazole was enhanced with the increasing of SBE-β-CD concentration and pH value. The dissolution at 5 min of the inclusion complexes was 93% in the pH 6.8 medium, which was significantly higher than that of pure drug or physical mixture of lansoprazole and SBE-β-CD (0.04% or 6%).
  • ZHAO Mingfei1, HAN Gang1, LI Huilan2, CHEN Yanhua2, LIU Zhanjun2*
    2015, 46(2): 172-175.
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    Ibuprofen-grafted chitosan oligosaccharide (COS-g-IBU) was synthesized with 1-(3-dimethylaminopropyl)- 3-ethylcarbodiimide hydrochloride (EDC·HCl) as coupling agent. Then this material self-assembled to produce the blank nanoparticles (COS-g-IBU NPs). The curcumin-loading COS-g-IBU NPs were prepared by ultrasonic irradiation technology. The results showed that the critical micelle concentration (CMC) of blank COS-g-IBU NPs was (24.6±0.2)μg/ml. The blank and drug-loading nanoparticles were both spherical with the mean size of 80 and 132 nm. The encapsulation efficiency and drug loading of the nanoparticles was (96.35±0.32)% and (8.79±0.03)%. The results of in vitro release test showed that the nanoparticles exhibited a significant sustained-release effect.
  • SUN Yu1, ZHANG Xinming2, CHEN Yunyan1, TANG Lin1, ZHOU Lingyun1
    2015, 46(2): 176-179.
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    The prodrug PEG-PLA-PTX was synthesized by condensation of paclitaxel with carboxyl-terminated copolymer PEG-PLA through ester-bond formation with an overall yield of about 56%. The PEG-PLA-PTX was found to have a critical micelle concentration (CMC) of 3.98×10-4 g/L. The results of in vitro release  experiments showed that the product could slowly release paclitaxel in pH 7.4 phosphate buffer (PBS). In vitro antitumor assay indicated that PEGPLA- PTX had cytotoxic activity against nasopharyngeal carcinoma LMP1 cells
  • ZHANG Xiqian1, ZHANG Jundong2, ZHAO Ping1, JIANG Xuehua1, WANG Ling1*
    2015, 46(2): 180-185.
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    A LC-MS/MS method was established for the determination of tenofovir in human plasma. The bioequivalence and the pharmacokinetic differences after oral administration of tenofovir disoproxil fumarate tablets to human under fasting and fed conditions were also investigated. A randomized two-way crossover trial was conducted in 48 healthy male volunteers, which were randomly divided into two groups, and further divided into two sub-groups. Subjects received a single oral dose of either test or reference formulations 300 mg under fasting and fed conditions, and crossly received the reference or test formulations after one-week washout period, respectively. The pharmacokinetic parameters of the test and reference formulations under fasting conditions were as follows: tmax(0.86±0.53) and (0.93± 0.37)h, cmax(487.6±147.2) and (443.1±131.3)ng/ml, t1/2(20.09±3.97) and (20.39±4.78)h, respectively. The relative bioavailability of the test formulation was (103.38±23.53)% calculated in AUC0→∞. The pharmacokinetic parameters of the test and the reference formulations under fed conditions were as follows: tmax(1.34±0.45) and (1.28±0.36)h, cmax(410.3±118.1) and (379.3±88.7)ng/ml, t1/2(15.57±4.12) and (16.47±4.96)h. The relative bioavailability of the test formulation was (107.91±15.34)% calculated in AUC0→∞. These findings indicated that the test and reference tablets of tenofovir disoproxil fumarate were bioequivalent in healthy volunteers in the trial under both fasting and fed conditions.
  • ZHENG Xueyan1, WANG Xiuli2, LI Yan3, LIU Linghua1, WANG Min1
    2015, 46(2): 186-189.
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    A LC-MS/MS method was established for the determination of amodiaquine (1) in whole blood from healthy volunteers, and its pharmacokinetics was studied. Hydroxychloroquine was used as the internal standard. An Agilent Zorbax SB C18 column was used, with the mobile phase of acetonitrile∶20 mmol/L ammonium acetate solution (23∶77), in the application of APCI source, in MRM and positive ionization mode, with the ion transitions of m/z
    356.3→m/z 283.2 (1) and m/z 336.0→m/z 247.1 (internal standard). The calibration curve of 1 was linear in the concentration range of 0.5 - 100 ng/ml. The intra- and inter-day RSDs were less than 10.0%, and the extraction recovery was more than 70.4%. The main pharmacokinetic parameters of 1 in 18 male healthy volunteers after oral administration of artesunate and 1 hydrochloride tablets were as follows: cmax (25.9±4.7) ng/ml,tmax (1.1±0.3) h, t1/2 (13.9±3.9) h, AUC0→t (294.5±42.8) ng·h·ml-1, AUC0→∞ (310.3±45.0) ng·h·ml-1.
  • GONG Ying1,2, HE Wenjuan1,2, WANG Weimei1,2, ZHANG Zhiqing1*
    2015, 46(2): 190-192.
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    The effect of imrecoxib on CYP2C9 enzyme in rats was evaluated by probe drug. Rats were randomly divided into the test group and the control group with 18 rats in each. Rats in test group were given imrecoxib intragastrically, and those in control group were given equal volume of distilled water, twice daily for 7 days. On d8, each rat was given tolbutamide intragastrically. The blood samples were collected from epicanthal folds within 24 h after administration of tolbutamide, and the concentrations of tolbutamide were determined by HPLC. The pharmacokinetic parameters of the two groups were calculated and the statistic analysis was processed. There were significant differences between the AUC0→24 h, AUC0→∞, tmax, CL and V of test group and control group(P<0.05). The AUC0→24 h and AUC0→∞ of tolbutamide in test group decreased significantly compared with those of the control group, while the CL of tolbutamide increased apparently. It indicated that imrecoxib could induce the activity of CYP2C9 enzyme and increase the metabolism of tolbutamide.
  • QIN Feng, ZHAO Jingdan, LIU Hao, WEN Hongliang, YANG Meicheng*
    2015, 46(2): 193-196.
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    An HPLC coupled with pulsed amperometric detection (PAD) method was established for the determination of gentamicin C and its related substances. A hydrophilic C18 column was used, with the mobile phase of 50 mmol/L sodium hydroxide solution (containing 0.7% trifluoroacetic acid and 0.025% pentafluoropropanoic acid, pH 2.6)∶acetonitrile (98.5∶1.5). The working electrode was golden electrode, with working mode of a four potential waveform. It was linear for gentamicin C1, C1a, C2 and C2a in the ranges of 6.233 - 249.3、5.819 - 232.8、6.923 - 276.9 and 4.002 - 160.1 μg/ml, respectively. Their recoveries were 99.0% - 102.8%, with RSDs of 1.3% - 2.2%.
  • LI Ji, LI Xia, LUO Jing, XU Changgen, LIU Haijing
    2015, 46(2): 197-198.
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    An ion chromatography method was established for the determination of sulfamate and sulphate in topiramate bulk drug. A conductivity detector and A Supp 7-250 anion analytical column were used with the eluent of sodium carbonate (5.0 mmol/L)-sodium bicarbonate (3.0 mmol/L) solution∶acetone (95∶5). The calibration curves for sulfamate and sulphate were both linear in the concentration range of 0.5 - 20.0 μg/ml. Their average recoveries were 100.4% and 101.5%, with RSDs both of 0.7%.
  • OUYANG Danwei1, SHAO Yan1, KONG Deyun1, SUI Donghu2*, LIU Xiaokun3
    2015, 46(2): 199-203.
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    An HPLC method was used to determine the content change of lobaplatin in 0.9% sodium chloride injection or in 5% glucose injection stored at different temperatures and concentrations for 24 h. The results showed that lobaplatin in 0.9% sodium chloride injection was stable for 4 h when stored at 25, 37 and 42 ℃, while in 5% glucose injection lobaplatin was stable for 2 h at 25 and 37 ℃. The decomposition products of 1 were also studied by HPLC. Lactic acid was found when stored in both solution, and its content would increase along with time.
  • QIAO Hongqun, WANG Lijia, FU Xiuzhi
    2015, 46(2): 204-206.
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    An HPLC method was established for the determination of clevidipine butyrate injection. A Venusil-XBP C18 column was used, with the mobile phase of phosphate buffer(ammonium dihydrogen phosphate 1.15 g, dissolved in water 900 ml, adjusted to pH 4.0 with phosphoric acid, and adjusted to 1 L with addition of water)∶acetonitrile (45∶55), at the detection wavelength of 240 nm. It was linear in the range of 5 - 200 μg/ml. The average recovery was 103.5%, with RSD of 1.6%.
  • CHEN Haiyan1, HU Qin2*
    2015, 46(2): 207-211.
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    Quantum dots (semiconductor nanocrystallites) have aroused great attention as a new fluorescent probe to detect biological samples. The characteristics of the quantum dots are superior in many ways. They can detect proteins, DNA, adenosine monophosphate, vitanuic C, Escherichia coli., Staphylococcus aureus, etc. The above applications as well as the prospects were summarized in this paper.
  • LI Chengwen1,2, LIU Xinyong1*
    2015, 46(2): 212-214.
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  • ZHOU Bin1,2, WU Xiaoming1*
    2015, 46(2): 215-219.
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