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    特约稿
  • 特约稿
    Targeting Angiogenesis for Cancer Therapy: Principle and Existing Problems
    CHEN Zhaocong
    2012, 31(11): 1389-1395.
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    As tumor angiogenesis plays a pivotal role in cancer progression and metastasis, targeting tumor associated angiogenesis should be a promising strategy for holding back tumor progression. This idea first articulated by Dr. Folkman followed by the discovery of several angiogenesis molecules had created an intense interest in both the academy and industry. Several targeting drugs had been approved by Food and Drug Administration (FDA, USA), and additional dozens are being put into I/II or III clinical trials. Unfortunately, the clinical effectiveness has been below expectation indicating our understanding of tumor cell biology is still inadequate； however, the visionary hypotheses of antiangiogenesis as a novel means for cancer treatment and issues occurred in clinical practice thereafter have been arousing profound influence in the future cancer research. The paper briefly reviewed the basic knowledge of tumor associated angiogenesis and discussed some existing problems.
    • 药物研究
  • 药物研究
    Solubility and Pharmacokinetics Study of Valacyclovir Hydrochloride
    HU Fan;ZHAO Rui;ZHANG Li;SONG Junke;LU Yang;DU Guanhua
    2012, 31(11): 1396-1400.
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    ObjectiveTo study the bioavailability and solubility of valacyclovir hydrochloride for enhancing quality standards. MethodsThe solubility was determined and compared for the crystal form Ⅰ,Ⅳ,Ⅷ of valacyclovir hydrochloride, the latter of which were administered to SD rats at the dose of 100 mg•kg－1. And a HPLC method was established to test the plasma level of valacyclovir hydrochloride. ResultsThe form Ⅷ was the most soluble form among the three forms in the six solvents. The indirect pharmacokinetic parameters of acyclovir,as the metabolites of the form Ⅰ,Ⅳ,Ⅷ of valacyclovir hydrochloride were as follows: Cmax was (10.304±5.246),(9.321±3.701) and (10.365±6.787) mg•L－1，respectively(P＞0.05)； AUC0→t was (20.167±1.775), (22.337±5.166) and (20.289±7.845) mg•L－1•h，respectively(P＞0.05). ConclusionThere is certain difference in solubility of valacyclovir hydrochloride among form Ⅰ,form Ⅳ and form Ⅷ, but no significant difference is found in biological actions in the body among them.
  • 药物研究
    Relative Bioavailability and Bioequivalence of Zopiclone Tablets in Healthy Volunteers
    CHEN Qian;LIU Yu;REN Xiu-hua;ZHANG Donglin;LIU Dong
    2012, 31(11): 1400-1403.
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    ObjectiveTo investigate the pharmacokinetics and bioequivalence of zopiclone test and control tablets in health volunteers. MethodsA single oral dose of 15 mg zopiclone test or control tablets were given to 20 healthy male volunteers in a randomized, twoway crossway study. HPLC fluorescence detector was used to determine the concentration of zopiclone in plasma. By the DAS 2.1 pharmacokinetic software, the pharmacokinetic parameters of the two preparations were calculated and the bioequivalence of two tablets was evaluated. ResultsThe main pharmacokinetic parameters of test and control preparations were as follows： t1/2 were (4.93±2.45) and (5.46±2.51) h； Cmax were (101.18±23.47) and (105.39±35.21) ng•mL－1； tmax were(1.60±1.16) and (1.64±1.35) h； AUC024 were (612.66±157.35) and (617.27±207.11) ng•h•mL－1； AUC0∞ was (664.88±160.27) and (679.12±223.75) ng•h•mL－1； The relative bioavailability of test preparations (F0t) was calculated to be (105.1±28.9)% according to AUC0t. ConclusionThe two kinds of domestic preparations are bioequivalent.
  • 药物研究
    Effect of Renshujianwei Granula on MMP-2 of CAG Rats with Spleenqi Deficiency Syndrome
    CHAO Lei;WANG Jiankun;ZHU Xuanxuan;NI Wenpeng;WANG Haidan;SHI Linfeng
    2012, 31(11): 1404-1407.
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    ObjectiveTo investigate the effects of Renshujianwei granula on matrix metalloproteinase 2 (MMP2) in rats with spleenqi deficiency syndrome chronic atrophy gastritis (CAG).MethodsSpleenqi deficiency syndrome of the CAG model was established, except for the normal control. The model rats were randomly divided into the model control group (0.9% sodium chloride solution), the weifuchun group(0.86 g•kg－1), the highdose (12 g•kg－1), middledose (6 g•kg－1) and lowdose (3 g•kg－1) of Renshujianwei granula groups. Rats were i.g. treated for consecutive five weeks. All of the rats were sacrificed by the tenth weekend. The quality of spleen weighed, the gastric mucosa tissue was macroscopically observed and the expression of MMP2 was detected by rapid immunohistochemistry. ResultsGastric mucosa was deep claybank in the model group, in which the expression of MMP2 was higher than that of the normal (P＜0.01). In comparison to the model group, MMP2 were significantly decreased in the highdose, middledose and lowdose of Renshujianwei granula groups as（2.20±1.30）,（1.20±0.45）,（2.60±1.95）(P＜0.01 or P＜0.05) , respectively, and the gastric mucosa of which presented as a small amount light yellow, some yellowish, and large number yellow, respectively. ConclusionThe therapeutic effect of Renshujianwei granula for CAG is associated with a reduction of MMP2 expression in gastric mucosa.
  • 药物研究
    Potency Comparation of Different Extracts from Yinchenhao Decoction on the Mice Jaundice Model
    AN Liping;DOU Zhihua;LUO Lin;CHEN Min;YANG Aihua
    2012, 31(11): 1407-1409.
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    ObjectiveTo screen the liver protection and jaundice elimination fraction of yinchenhao decoction(YCHD). MethodsThe mice jaundice model was induced by i.g. alphanaphthylisothiocyanate (ANIT). The total bilirubin(TBiL), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bile acid (TBA) in the serum were determined after intragastric administration of low, middle, and high dose of 75% ethanol extract of YCHD(EE) and water extract of the residue of YCHD extracted by ethanol(WE), respectively. And the bile secretion of mice was determined as well.ResultsCompared with the model group, TBiL, ALP, ALT and TBA of low dose EE group and TBiL, ALP, ALT of high dose WE group decreased significantly (P＜0.01 or P＜0.05). In addition, bile secretion of the low and middle EE groups, high dose WE group increased significantly (P＜0.05). ConclusionBoth EE and WE of YCHD decoction possess the liver protection and jaundice retreating effect on ANITinduced jaundice model of mice.
  • 药物研究
    Determination of ED50 of Convulsion Induced by Ropivacaine in Rats at Different Developing Stage with Sequential Experimental Method
    OU Yijin;XU Shiyuan
    2012, 31(11): 1409-1412.
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    ObjectiveTo detect the median effective dose (ED50) of i.p.ropivacaine in rats under developmental phase by sequential experimental method. MethodsFortyfour SD rats were randomly divided into two groups:15dayold group(group D15, n＝22) and 60dayold group(group D60, n=22). The dosage of ropivacaine was determined by sequential experimental method. The behavior of rats were observed after intraperitoneal administration. Convulsion was defined if it achieved classification Ⅲ or more within 30 minutes. The ED50 and 95% confidence interval were calculated. ResultsThe ED50 of group D15 was 54.95 mg•kg－1 and the 95% confidence interval was 50.52－59.77 mg•kg－1； while the ED50 of group D60 was 34.36 mg•kg－1 and 95% confidence interval was 31.81－37.11 mg•kg－1. The lgED50 of two groups showed statistical significant difference. ConclusionThe sequential experimental method for determination of ED50 of ropivacaine causing convulsion is simple, fast and effective. The convulsion ED50 of ropivacaine in 15dayold rats is much higher than that in 60dayold rats.
  • 药物研究
    Preliminary Study on Material Basis of Asari Radix et Rhizoma Against Asthma and Cough
    LIU Jing;MENG Li;YUAN Zimin;ZHANG Huizong
    2012, 31(11): 1412-1415.
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    ObjectiveTo explore the material basis of Asari Radix et Rhizoma for relieving asthma and cough.MethodsTo establish the HPLC finger prints of different extracts which were isolated with a gradient series of solvents. The relationship of cough relieving and asthma preventing with relative peak areas in the finger prints was analyzed to priliminarily determine active components. ResultsThe extracts, HPLC finger prints of Asari Radix et Rhizoma and correlation coefficient of 41 chromatographic peaks were obtained. ConclusionThe constituents corresponded to 12 chromatographic peaks are active basis of Asari Radix et Rhizoma, in which X21 is Methyl eugenol and 11 activity constituents are detected in HPLC finger prints of Asari Radix et Rhizoma gel.
  • 药物研究
    Intervention and Possible Mechanism of Calcium Dobesilate on Doxorubin-induced Nephropathy Rats
    ZHANG Chengzhen;ZHANG Yuxia
    2012, 31(11): 1416-1422.
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    ObjectiveTo investigate the effects and possible mechanism of calcium dobesilate on indicators of serum and urine，renal pathology，fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 4 (FGFR4) in doxorubininduced nephropathy rats. MethodsDoxorubin nephropathy was induced by a tail intravenous injection of doxorubin. The rats were randomly divided into the normal group，model group and treatment group. Serum index and 24 h urine protein were measured after calcium dobesilate being treated for 2，4，6 weeks. The kidney tissues were collected for observation under the light microscope and electron microscope. The expression of FGF2 and FGFR4 in renal tissue were detected by immunohistochemistry SABC. ResultsThe general condition and body weight were significantly improved after being treated with calcium dobesilate for 2，4，6 weeks. Compared with the model group，the urine protein，TG，TC，the expression of FGF2 and FGFR4 were significantly reduced，serum albumin were significantly raised，SCr and BUN alterations were not statistically obvious. There was no conspicuous pathological change under the light microscope. The podocyte was showed widely fused under the electron microscope. The renal pathology improved significantly after the treatment of calcium dobesilate. Besides，FGF2 and FGFR4 closely correlated to urine protein with the progession of doxorubin nephropathy（rFGF2=0.960，rFGFR4=0.984）. ConclusionCalcium dobesilate is effective for treating doxorubin caused nephropathy rats, the mechanism of which could be associated with FGF2 and FGFR4 reduction.
  • 药物研究
    Determination of Cefcapene in Human Plasma By LCMS/MS
    WANG Meng;ZHOU Wenjia;HUANG Ming;ZHANG Quanying
    2012, 31(11): 1423-1425.
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    ObjectiveTo establish a method for determinating cefcapene by LCMS/MS. MethodsThe plasma samples were precipitated for protein with methanol. Methanol  2.5 mmoL•L－1 ammonium acetate (32：68) were used as mobile phase. The analysis was performed on Waters Symmetry C18 column (3.9 nm×150 mm, 5 μm). The samples were measured by a triple  quadrupole mass spectrometer in negative electron spray ionization (ESI) mode using multiple reaction monitoring (MRM). The extracted ions monitored following MRM transitions were m/z 452.1→348.1 for cefcapene and m/z 409.1→270.0 for the internal standard cefradine. ResultsThe calibration curve of cefcapene in human plasma was in linear relationship over the concentration rang of (3.600－3 600) μg•L－1. The lower limit of quantitation was 3.600 μg•L－1. The RSD of intraday was less than 4.3%. The RSD of interday was less than 2.1% . The recovery was 97.0%－102.5%. ConclusionThe method is proved to be convenient, sensitive and accurate, which can be used to study the pharmacokinetics of cefcapene pivoxil hydrochloride tablets in healthy volunteers.
    • 药物与临床
  • 药物与临床
    Fortyfive Cases of Therapeutic Treatment for Vascular Dementia by Fasudil Hydrochloride
    ZHANG Xiaoqiao;LI Li
    2012, 31(11): 1438-1440.
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    ObjectiveTo evaluate the therapeutic efficacy of fasudil hydrochloride on patients with vascular dementia (VaD) and the changes of serum interleukin6 (IL6), matrix metalloproteinase9 (MMP9) levels. MethodsThe total of 90 patients with VaD were randomly divided into the treatment group and control group (45 patients each). Patients in the control group were given with regular treatment. Patients in the treatment group were given with fasudil hydrochloride injection for 4 weeks. Before and after treatment, the cognitive function and daily living activities of patients were assessed with mini mental status examination (MMSE) and clinical dementia rate (CDR) scale. Enzymelinked immunosorbent assay（ELISA）was used to detect the concentration of serum IL6, MMP9. ResultsTo compare with the control group, the MMSE score was higher and the ADL score was lower in the treatment group (P＜0.05). The IL6, MMP9 levels in treatment group were lower than those of the control group (P＜0.05). ConclusionFasudil hydrochloride is efficient to improve the cognitive function and living activities of patients with VaD, which may be associated with suppressing inflammatory and attenuating secondary injury to brain cells.
    • 药物制剂与药品质量控制
  • 药物制剂与药品质量控制
    Rapid Determination of Moisture Content in Pogostemon cablin by NearInfrared Spectroscopy
    CAI Jialiang;LI Leilei;JI Shengguo
    2012, 31(11): 1468-1470.
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    ObjectiveTo establish a method for quantitative determination of the moisture content in Pogostemon cablin(Blanco) Benth by nearinfrared spectroscopy and make a rapid test. MethodsMoisture contents of 142 samples were determined by a vacuumc drying method. The quantitative detest model for moisture content in Pogostemon cablin(Blanco) Benth was established by using multiplicative signal correction (MSC) , nearinfrared spectroscopy pretreated with firstderivative and partial least squares method.ResultsThe internal crossvalidation determination coefficient was 0.968 67, with corrected meansquare error as 0.241, predicted meansquare deviation as 0.308, and internal crossvalidation mean square error as 0.430 in the created calibration model. ConclusionThis quantitative model by nearinfrared spectroscopy is steady，accurate and reliable, which can be applied to rapid determination of moisture content in Pogostemon cablin(Blanco) Benth.
  • 药物制剂与药品质量控制
    Optimization of Freezedrying Process for Preparation of Oxaliplatin Loaded Nanostructured Lipid Carriers for Injection
    QIU Lipeng;YANG Lei;LONG Miaomiao;LIU Ying;WANG Dongkai;ZHOU Hui
    2012, 31(11): 1471-1473.
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    ObjectiveTo investigate the freezedrying formulations of oxaliplatin in oxaliplatinloaded nanostuctured lipid carriers( OPNLC) for injection. MethodsThe optimum freezedrying preparation and techniques were established by single factor experiments and the characters were evaluated. ResultsThe optimal freezedrying technology was determined with 5% of mannitol as protective agent. No significant changes were found in the mean particle size, Zeta potential and EE%, which were （124±16） nm versus （115±17） nm, －10.8 mV versus －16.0 mV, and 67.3% versus 72.6% post and pre freezedrying, respectively. ConclusionThe stable freezedrying preparation of OPNLC could be prepared under the optimal condition.
  • 药物制剂与药品质量控制
    Study on Quality Standard of Santeng Tablets
    SHEN Xiong;YANG Chunxin;LIANG Jian;LV Qianzhou
    2012, 31(11): 1474-1476.
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    ObjectiveTo establiah a quality standard for Santeng tablets. MethodsTripterygium wilfordii, sargentgloryvine stem and caulis spatholobi in the formula were indentified by thin layer chromatography(TLC) and the triptolide was determined by HPLC. ResultsThe characteristic spots of tripterygium wilfordii, caulis spatholobi and sargentgloryvine stem can be detected by TLC. Triptolide presented a linear range from 0.816～8.160 μg, with correlation coefficient (r) as 0.999. The average recovery and RSD were 97.19% and 1.62%，respectively. ConclusionThis method is simple，reliable and reproducible，and can be used for the quality control of the preparation.
  • 药物制剂与药品质量控制
    Formulation Optimization of Felodipine Extendedrelease Tablets by Central Composite Designresponse Surface Methodology
    XIE Xiangyang;ZHANG Hong;YANG Xiaosong;LIU Zuxiong;CHEN Ying
    2012, 31(11): 1477-1480.
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    ObjectiveThe purpose of this study was to optimize the formulation of the felodipine extendedrelease tablets. MethodsThe felodipine extendedrelease tablets were prepared by employing the mixture of hydroxypropyl methylcellulose (HPMC) K4M and HPMC 100LV as the basic matrix materials. Factors that affected drug release were investigated. Thereafter，a central composite designresponse surface methodology (CCDRSM) was applied to optimize the formulation of the felodipine extendedrelease tablets. The release rate of the extendedrelease tablets and control tablets were compared by a similarity factor ( f2 value). ResultsThe optimized formulation contained 20.0% of HPMC K4M and 10.0% of HPMC 100LV of the total weight and accumulative release percentages at 1，4，8 h were consistent with the criteria，which was 5%～30%，45%～70%，no less than 80%， respectively. The f2 for the extendedrelease tablets and control tablets in different solvents were 70.87， 74.19， 59.68， 69.25. ConclusionCombing HPMC K4M and HPMC 100LV at a certain rate can effectively control drug release and the central composite designresponse surface methodology is successfully used to optimize the formulation of felodipine extendedrelease tablets, which complying with requirements of the USP.
  • 药物制剂与药品质量控制
    Determination of 12 Kinds of Pesticide Residues in Dendrobium Officinale Prescription by HPLC/MS/MS
    FANG Cuifen;TAN Chunmei;MA Linke;ZHU Ming
    2012, 31(11): 1481-1484.
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    ObjectiveTo establish a method for the simultaneous determination of 12 kinds of pesticide residues in the Dendrobium officinale prescription. MethodsThe total of 12 pesticides was extracted by ultrasonic, and then purified through Carb/NH2 solid phase extraction(SPE) cartridges. The residues were simultaneous identified and quantified by HPLC/MS/MS. ResultsThe recoveries ranged from 72.1%～119.5%, with their relative standard deviations(RSDs) being less than 15%. The limit of detection (LOD) for each pesticide was below 0.001 mg•kg－1. ConclusionThis method was simple, sensitive and reproducible, which could be appilied to determine 12 kinds of pesticide residues in Dendrobium officinale prescription.
  • 药物制剂与药品质量控制
    Determination of Content and Related Substances of Chlortetracycline Hydrochloride Solution by HPLC
    MA Yonggui;LI Ziming;WANG Qiulan;HE Guofang
    2012, 31(11): 1485-1487.
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    ObjectiveTo establish a HPLC method for determination of the content and related substances of chlortetracycline hydrochloride solution.MethodsThe HPLC system consisted of C18 column (pH＞8, 4.6×250 mm,5 μm), 0.05 mol•L－1 ammonium oxalate solutiondimethylformamide0.1 mol•L－1 ammonium dibasic phosphate solution (56：40：4) (pH being adjusted to 8.3 with ammonia solution) as mobile phase, the flow rate was 0.9 mL• min－1. Detection wavelength was set at 370nm, the injection volume was 10 μL and column temperature was 40℃.ResultsThe calibration curve was linear in the range of 0.006～0.096 mg•mL－1 (r = 0.999 8), the average recoveries were 100.5% (RSD=0.36%), 98.7% (RSD=1.04%), 100.9% (RSD=0.48%) (n=3), respectively. The limit of detection was 38.2 ng.ConclusionThe method was rapid, simple, accurate, sensitive and suitable for the content and related substances determination of chlortetracycline hydrochloride solution.
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