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Chen X.-H.,Chongqing Institute for Food and Drug Control | Chen X.-H.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | Su J.,Chongqing Institute for Food and Drug Control | Wang H.,Chongqing Institute for Food and Drug Control | And 3 more authors.
Chinese Traditional and Herbal Drugs | Year: 2014

Objective: To establish a UPLC method for the simultaneous determination of 11 components, such as chlorogenic acid, geniposide, baicalin, berberine, wogonoside, baicalein, aloe-emodin, wogonin, emodin, chrysophanol, and physcion in Zhizi Jinhua Pill (ZJP). Methods: The chromatographic separation was achieved on an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with acetonitrile (A)-0.1% phosphate acid solution (B) as mobile phase at the flow rate of 0.4 mL/min for gradient elution; The column temperature was 35°C. The determination wavelengths were 324 nm for chlorogenic acid, 238 nm for geniposide, 345 nm for berberine, 276 nm for baicalin, wogonoside, baicalein, and wogonin, and 254 nm for aloe-emodin, emodin, chrysophanol, and physcion. Results: The 11 compounds were well separated. The RSD values of precision and reproducibility were all less than 2%. The stability was good in 24 h. The linear relationship between the concentration and peak areas of the 11 compounds was all linear (r ≥ 0.9995). The average recoveries were between 98.68%-100.47% and the RSD values were all less than 1.5%. Conclusion: The method is simple, reliable, and accurate, and could be used for the quality control of ZJP.


Kou S.,Southwest University | Han B.,Southwest University | Wang Y.,Southwest University | Huang T.,Southwest University | And 7 more authors.
Life Sciences | Year: 2016

Aims Hyperlipidemia contributes to the progression of cardiovascular diseases. Main alkaloids from Rhizoma Coptidis including berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI) and jatrorrhizine (JAT), improved dyslipidemia in hypercholesterolemic hamsters to a different degree. In this study, HepG2 cells and hypercholesterolemic hamsters were used to investigate the synergetic cholesterol-lowering efficacy of these five main alkaloids. Main methods The cellular lipid and cholesterol accumulation and in HepG2 cells were evaluated by Oil Red O staining and HPLC analysis. LDL receptor, 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR) and cholesterol 7-alpha-hydroxylase (CYP7A1) that involving cholesterol metabolism in HepG2 cells were measured by qRT-PCR, western blot and immunofluorescence analysis. The serum profiles including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), as well as TC and total bile acids (TBA) of feces in hypercholesterolemic hamsters were also measured. Key finding As compared to single alkaloids, the combination of five main alkaloids (COM) reduced the lipid and cholesterol accumulation in HepG2 cells more effectively and performed an advantageous effect on controlling TC, TG, LDL-c and HDL-c in hypercholesterolemic hamsters. More effective reduction of TBA and TC levels in feces of hamsters were achieved after the administration of COM. These effects were derived from the up-regulation of LDL receptor and CYP7A1, as well as HMGCR downregulation. Significance Our results demonstrated that COM showed a synergetic cholesterol-lowering efficacy, which was better than single alkaloids and it might be considered as a potential therapy for hypercholesterolemia. © 2016 Elsevier Inc. All rights reserved.


Wu J.,Southwest University | Jiang H.,Southwest University | Bi Q.,Southwest University | Luo Q.,Southwest University | And 5 more authors.
Molecular Pharmaceutics | Year: 2014

Faced with the complex medical challenge presented by spinal cord injuries (SCI) and considering the lack of any available curative therapy, the development of a novel method of delivering existing drugs or candidate agents can be perceived to be as important as the development of new therapeutic molecules. By combining three ingredients currently in clinical use or undergoing testing, we have designed a central nervous system targeted delivery system based on apamin-modified polymeric micelles (APM). Apamin, one of the major components of honey bee venom, serves as the targeting moiety, poly(ethylene glycol) (PEG) distearoylphosphatidylethanolamine (DSPE) serves as the drug-loaded material, and curcumin is used as the therapeutic agent. Apamin was conjugated with NHS (N-hydroxysuccinimide)-PEG-DSPE in a site-specific manner, and APM were prepared by a thin-film hydration method. A formulation comprising 0.5 mol % targeting ligand with 50 nm particle size showed strong targeting efficiency in vivo and was evaluated in pharmacodynamic assays. A 7-day treatment by daily intravenous administration of low doses of APM (corresponding to 5 mg/kg of curcumin) was performed. Significantly enhanced recovery and prolonged survival was found in the SCI mouse model, as compared to sham-treated groups, with no apparent toxicity. A single dose of apamin-conjugated polymers was about 700-fold lower than the LD50 amount, suggesting that APM and apamin have potential for clinical applications as spinal cord targeting ligand for delivery of agents in treatment of diseases of the central nervous system. © 2014 American Chemical Society.


Wu J.-J.,Southwest University | Wu J.-J.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | Wang W.-T.,Southwest University | Wang M.,Southwest University | And 4 more authors.
International Journal of Electrochemical Science | Year: 2016

Tanshinone IIA (TAN), an insoluble drug prepared to form micro-emulsion, was electrochemically investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) at glassy carbon electrode. Its electrochemical behavior was proved to be quasi-reversible in acetate buffer (pH4.0), besides, on the basis of CV, the electrochemical redox mechanism of TAN has proved two protons and two electrons involved in the electrode surface reaction. DPV method was developed for its quantitative determination in real sample, and the linear relationship between the peak current and the TAN concentration was obtained in the concentration range of 0.2 to 1.2 μg/mL with a detection limit of 50.25 ng/mL. The reproducibility and repeatability of the method were determined and validated feasibly. The accepted RSD (1.82%) and recovery studies (96.01-101.23%) were obtained, and the result was agreed well with that by HPLC. The present study provides guidance for TAN electrochemical behavior investigation and direct determination of micro-emulsion. © 2016 The Authors.


Mao K.,Southwest University | Mao K.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | Ma Y.-X.,Southwest University | Ma Y.-X.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | And 4 more authors.
Chinese Journal of New Drugs | Year: 2015

Iron deficient anemia is one of the common diseases which are serious threats to human health worldwide. The traditional treatment, oral iron, has gastrointestinal side effects, poor absorption, and low effectiveness; while intravenous iron treatment with polysaccharide iron complex as the main active ingredient can work rapidly and safely. After the development of more than half a century, intravenous iron has been widely used in clinic. Especially with the listing of several new products in recent years, intravenous iron ushered in the new vigorous development. In this article, research progress of new types of intravenous iron was reviewed in detail. ©, 2015, Chinese Journal of New Drugs Co. Ltd. All right reserved.


Zhang Y.,Southwest University | Deng C.,Southwest University | Liu S.,Southwest University | Wu J.,Southwest University | And 5 more authors.
Angewandte Chemie - International Edition | Year: 2014

Inspired by the knowledge that most antibodies recognize a conformational epitope because of the epitope's specific three-dimensional shape rather than its linear structure, we combined scaffold-based peptide design and surface molecular imprinting to fabricate a novel nanocarrier harboring stable binding sites that captures a membrane protein. In this study, a disulfide-linked α-helix-containing peptide, apamin, was used to mimic the extracellular, structured N-terminal part of the protein p32 and then serve as an imprinting template for generating a sub-40 nm-sized polymeric nanoparticle that potently binds to the target protein, recognizes p32-positive tumor cells, and successfully mediates targeted photodynamic therapy in vivo. This could provide a promising alternative for currently used peptide-modified nanocarriers and may have a broad impact on the development of polymeric nanoparticle-based therapies for a wide range of human diseases. Magic bullet: A peptide served as an "indirect" targeting ligand to mediate active tumor-targeted drug delivery. A disulfide-linked α-helix containing peptide, apamin, was used to mimic the extracellular, structured N-terminal part of the protein p32. The combination with surface molecular imprinting produced a nanocarrier that recognizes p32-positive tumors in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Xie Z.,Southwest University | Xie Z.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | Wei L.,Southwest University | Wei L.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | And 8 more authors.
Iranian Journal of Pharmaceutical Research | Year: 2016

The objective of the study was to develop a simple, specific and stability-indicating HPLC method for the simultaneous determination of creatine phosphate sodium (CPS) and its related substances in pharmaceutical formulation. Separation of creatine phosphate sodium from its major process impurities and degradation products was achieved on a Hypersil BDS C18 column (250 × 4.6 mm, 5 μm) with an aqueous mobile phase containing 0.2% (w/v) tetrabutylammonium hydroxide (TAH) and 0.2% (w/v) monopotassium phosphate adjusted to pH 6.6 with orthophosphoric acid at a flow rate of 1.0 mL min-1. The analytes were detected at 210 nm. Different chromatographic parameters were carefully optimized. The relative response factors for creatine, creatinine and creatinine phosphate disodium salt relative to CPS were determined. The method has been validated with respect to solution stability, system suitability, LOD, LOQ, linearity, accuracy, precision, specificity and robustness. The validation criteria were met in all cases. The developed method was successfully applied to determine the purity of CPS in pharmaceutical formulation. © 2016 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services.


Yu J.-W.,Chongqing Fuling Pharmaceutical Co. | Deng K.-Y.,Chongqing Institute of Food and Drug for Control | Deng K.-Y.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | Peng T.,Chongqing Fuling Pharmaceutical Co. | And 2 more authors.
Zhongguo Zhongyao Zazhi | Year: 2013

Objective: To develop a UPLC method for the simultaneous determination of liquiritin, narirutin, hesperidin, ammonium glycyrrhetate, honokiol and magnolol in Huoxiang Zhengqi oral liquid. Method: A Zorbax Eclipse C18column was used with the mobile phase of acetonitrile and 0.05% phosphate acid by gradient elution at the detection wavelength of 220 nm. The flow rate was 0.42 mL· min-1 and the column temperature was 30°C. Result: The calibration curves were linear in the ranges of 0.001 7-0.034, 0.003 4-0.068, 0.006 4-0.128, 0.012 8-0.256, 0.003 2-0.064, 0.006 4-0.128 μg, respectively. The average recoveries were 103.3%, 98.39%, 98.29%, 102.1%, 98.45%, 102.2% with RSDs of 2.1%, 1.0%, 0.50%, 2.3%, 0.9%, 2.0%, respectively. Conclusion: The UPLC method was simple, rapid and accurate, it could be used for quality control of Huoxiang Zhengqi oral liquid.


Li L.,Southwest University | Huang T.,Southwest University | Tian C.,Southwest University | Xiao Y.,Southwest University | And 7 more authors.
Life Sciences | Year: 2016

Aims This study is to investigate the effect of phellodendrine (PHE) against AAPH-induced oxidative stress and find out the biological mechanism of PHE by using the zebrafish embryo model. Main methods After treatments by AAPH or PHE, the mortality and heartbeat of zebrafish embryos were recorded and the production of reactive oxygen species (ROS), lipid-peroxidation and the rate of cell death were detected by fluorescence spectrophotometry respectively. Whereafter, the pathways of PHE against AAPH-induced oxidative stress were screened by inhibitors to explore its biological mechanism. The related genes and proteins expressions were analyzed by real-time quantitative reverse-transcription polymerase-chain-reaction (qRT-PCR) and western blotting. Key findings The PHE obviously improved the decreased survival rate and abnormally elevated heart-beating rate of zebrafish embryos caused by AAPH. Especially 200 μg/mL of PHE make the survival rate increased to 90.26 ± 1.40% at 72 hfp and the heartbeat back to normal. Besides, AAPH caused a significant increase in the production of reactive oxygen species (ROS), lipid-peroxidation and cell death rate, all of which could be decreased after PHE treatment dose-dependently. And PHE exerted the protective activity against AAPH-induced oxidative stress through down-regulating AKT phosphorylation and NF-kB3 expression, which associate with modulation of IKK phosphorylation in zebrafish embryos. Significance The PHE showed a good antioxidant effect in vivo, and the mechanism has been stated that the PHE can down-regulating AKT, IKK, NF-kB phosphorylation and COX-2 expression induced by AAPH. Moreover, the PHE also ameliorated the ROS-mediated inflammatory response. © 2016 Elsevier Inc.


Zou X.,Southwest University | Zou X.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | Tu G.,Southwest University | Tu G.,Chongqing Engineering Research Center for Pharmaceutical Process and Quality Control | And 2 more authors.
Bioprocess and Biosystems Engineering | Year: 2014

Polymalic acid (PMA) is a water-soluble polyester with many attractive properties for biomedical application. Its monomer l-malic acid is widely used in the food industry and also a potential C4 platform chemical. Cofactor and CO2 donor involved in the reductive routes were investigated for PMA production by Aureobasidium pullulans. Biotin as the key cofactor of pyruvate carboxylase was favor for the PMA biosynthesis. Na2CO3 as CO2 donor can obviously improved PMA titer when compared with no CO2 supplier NaOH, and also exhibit more advantages than the other donor CaCO3 because of its water-soluble characteristic. A combinational process with addition of biotin 70 mg/L and Na2CO3 as the CO2 donor was scaled-up in 50 L fermentor, achieving the high product 34.3 g/L of PMA and productivity of 0.41 g/L h. This process provides an efficient and economical way for PMA and malic acid production, and is promising for industrial application. © 2014 Springer-Verlag.

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