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PubMed | State University of New York at Stony Brook, Shandong University of Technology, Shandong University and Hebei Changshan Biochemical Pharmaceutical Co.
Type: | Journal: Carbohydrate research | Year: 2015

Low molecular weight heparins (LMWHs) are linear and highly charged carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. Compared to unfractionated heparin (UFH), LMWHs are prevalently used as clinical anticoagulant drugs due to their lower side effects and better bioavailability. The work presented herein provides a rapid and powerful fragment mapping method for structural characterization of LMWHs. The chain fragments of two types of LMWHs, enoxaparin and nadroparin, were generated by controlled enzymatic digestion with each of heparinase I (Hep I, Enzyme Commission (EC) # 4.2.2.7), heparinase II (Hep II, no EC # assigned) and heparinase III (Hep III, EC # 4.2.2.8). Reversed phase ion pair high performance liquid chromatography (RPIP-HPLC) coupled with electrospray ion trap time-of-flight mass spectrometry (ESI-IT-TOF-MS) was used to profile the oligosaccharide chains ranging from disaccharides to decasaccharides. A database containing all theoretical structural compositions was established to assist the mass spectra interpretation. The six digests derived by three enzymes from two types of LMWHs exhibited distinguishable fingerprinting patterns. And a total of 94 enoxaparin fragments and 109 nadroparin fragments were detected and identified. Besides the common LMWH oligosaccharides, many components containing characteristic LMWH structures such as saturated L-idopyranosuronic acid, 2,5-anhydro-D-mannitol, 1,6-anhydro-D-aminopyranose, as well as odd number oligosaccharides were also revealed. Quantitative comparison of major components derived from innovator and generic nadroparin products was presented. This approach to profile LMWHs fragments offers a highly reproducible, high resolution and information-rich tool for evaluating the quality of this category of anticoagulant drugs or comparing structural similarities among samples from various sources.


Luo H.,Jiangnan University | Ge L.,China Shijiazhuang Pharmaceutical Group Co. | Zhang J.,China Shijiazhuang Pharmaceutical Group Co. | Zhao Y.,Hebei Changshan Biochemical Pharmaceutical Co. | And 5 more authors.
PLoS ONE | Year: 2015

In this study, an efficient acetone-butanol-ethanol (ABE) fermentation strategy integrating Clostridium acetobutylicum/Saccharomyces cerevisiae co-culturing system with exogenous butyrate addition, was proposed and experimentally conducted. In solventogenic phase, by adding 0.2 g-DCW/L-broth viable S. cerevisiae cells and 4.0 g/L-broth concentrated butyrate solution into C. acetobutylicum culture broth, final butanol concentration and butanol/acetone ratio in a 7 L anaerobic fermentor reached the highest levels of 15.74 g/L and 2.83 respectively, with the increments of 35% and 43% as compared with those of control. Theoretical and experimental analysis revealed that, the proposed strategy could, 1) extensively induce secretion of amino acids particularly lysine, which are favorable for both C. acetobutylicum survival and butanol synthesis under high butanol concentration environment; 2) enhance the utilization ability of C. acetobutylicum on glucose and over-produce intracellular NADH for butanol synthesis in C. acetobutylicum metabolism simultaneously; 3) direct most of extra consumed glucose into butanol synthesis route. The synergetic actions of effective amino acids assimilation, high rates of substrate consumption and NADH regeneration yielded highest butanol concentration and butanol ratio in C. acetobutylicum under this stress environment. The proposed method supplies an alternative way to improve ABE fermentation performance by traditional fermentation technology. © 2015 Luo et al.


PubMed | Hebei Changshan Biochemical Pharmaceutical Co., China Shijiazhuang Pharmaceutical Group Co. and Jiangnan University
Type: Journal Article | Journal: PloS one | Year: 2015

In this study, an efficient acetone-butanol-ethanol (ABE) fermentation strategy integrating Clostridium acetobutylicum/Saccharomyces cerevisiae co-culturing system with exogenous butyrate addition, was proposed and experimentally conducted. In solventogenic phase, by adding 0.2 g-DCW/L-broth viable S. cerevisiae cells and 4.0 g/L-broth concentrated butyrate solution into C. acetobutylicum culture broth, final butanol concentration and butanol/acetone ratio in a 7 L anaerobic fermentor reached the highest levels of 15.74 g/L and 2.83 respectively, with the increments of 35% and 43% as compared with those of control. Theoretical and experimental analysis revealed that, the proposed strategy could, 1) extensively induce secretion of amino acids particularly lysine, which are favorable for both C. acetobutylicum survival and butanol synthesis under high butanol concentration environment; 2) enhance the utilization ability of C. acetobutylicum on glucose and over-produce intracellular NADH for butanol synthesis in C. acetobutylicum metabolism simultaneously; 3) direct most of extra consumed glucose into butanol synthesis route. The synergetic actions of effective amino acids assimilation, high rates of substrate consumption and NADH regeneration yielded highest butanol concentration and butanol ratio in C. acetobutylicum under this stress environment. The proposed method supplies an alternative way to improve ABE fermentation performance by traditional fermentation technology.


Sun M.,Hebei North University | Zhang P.,Hebei North University | Liu J.,Hebei Changshan Biochemical Pharmaceutical Co.
Proceedings - 2012 International Conference on Computer Science and Information Processing, CSIP 2012 | Year: 2012

Establishment of the evaluation system, conforming to students' realities with objective, impartial and easy operations, is a complex systematic engineering. It will help to reflect the learners' language ability, contribute to the coordination and unity of course objectives, teaching process and curriculum evaluation, and help to bring the positive feedback into play. This paper will discuss how to create a task-based teaching evaluation system in terms of different levels, diversification, formative assessment, summative assessment, and portfolios. © 2012 IEEE.


Liu J.-L.,Hebei Changshan Biochemical Pharmaceutical Co. | Sun M.-H.,Hebei North University | Ma J.-J.,Agricultural University of Hebei
Acta Crystallographica Section E: Structure Reports Online | Year: 2012

The title compound, C15H14N2O2, was obtained from the reaction of 3-hydroxybenzaldhyde and 4- methylbenzohydrazide in methanol. In the molecule, the benzene rings form a dihedral angle of 2.9 (3)°. In the crystal, N - H⋯O and O - H⋯O hydrogen bonds link the molecules into layers parallel to (101). The crystal packing also exhibits π-π interactions between the aromatic rings [centroid-centroid distance = 3.686 (4) Å].


Chi L.,Shandong University | Li D.,Shandong University | Chi L.,Ocean University of China | Jin L.,Shandong University | And 4 more authors.
Carbohydrate Polymers | Year: 2014

Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated and negatively charged, linear carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. They are widely used as anticoagulant drugs possessing better bioavailability, longer half-life, and lower side effects than heparin. Comprehensive structure characterization of LMWHs is important for drug quality assurance, generic drug application, and new drug research and development. However, fully characterization of all oligosaccharide chains in LMWHs is not feasible for current available analytical technologies due to their structure complexity and heterogeneity. Fingerprinting profiling is an efficient way for LMWHs' characterization and comparison. In this work, we present a simple, sensitive, and powerful analytical approach for structural characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were analyzed using reversed phase ion pair electrospray ionization mass spectrometry (RPIP-ESI-MS). More than 200 components were identified, including major structures, minor structures, and process related impurities. This approach is robust for high resolution and complementary fingerprinting analysis of LMWHs. © 2013 Elsevier Ltd. All rights reserved.


Xu X.,Shandong University | Li D.,Shandong University | Chi L.,State University of New York at Stony Brook | Du X.,Hebei Changshan Biochemical Pharmaceutical Co. | And 2 more authors.
Carbohydrate Research | Year: 2015

Low molecular weight heparins (LMWHs) are linear and highly charged carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. Compared to unfractionated heparin (UFH), LMWHs are prevalently used as clinical anticoagulant drugs due to their lower side effects and better bioavailability. The work presented herein provides a rapid and powerful fragment mapping method for structural characterization of LMWHs. The chain fragments of two types of LMWHs, enoxaparin and nadroparin, were generated by controlled enzymatic digestion with each of heparinase I (Hep I, Enzyme Commission (EC) # 4.2.2.7), heparinase II (Hep II, no EC # assigned) and heparinase III (Hep III, EC # 4.2.2.8). Reversed phase ion pair high performance liquid chromatography (RPIP-HPLC) coupled with electrospray ion trap time-of-flight mass spectrometry (ESI-IT-TOF-MS) was used to profile the oligosaccharide chains ranging from disaccharides to decasaccharides. A database containing all theoretical structural compositions was established to assist the mass spectra interpretation. The six digests derived by three enzymes from two types of LMWHs exhibited distinguishable fingerprinting patterns. And a total of 94 enoxaparin fragments and 109 nadroparin fragments were detected and identified. Besides the common LMWH oligosaccharides, many components containing characteristic LMWH structures such as saturated l-idopyranosuronic acid, 2,5-anhydro-d-mannitol, 1,6-anhydro-d-aminopyranose, as well as odd number oligosaccharides were also revealed. Quantitative comparison of major components derived from innovator and generic nadroparin products was presented. This approach to profile LMWHs' fragments offers a highly reproducible, high resolution and information-rich tool for evaluating the quality of this category of anticoagulant drugs or comparing structural similarities among samples from various sources. © 2015 Elsevier Ltd. All rights reserved.


Liu Z.,Shandong University | Ji S.,Hebei Changshan Biochemical Pharmaceutical Co. | Sheng J.,Shandong University | Wang F.,Shandong University
Drug Discoveries and Therapeutics | Year: 2014

Heparin, one of the common anticoagulants, is clinically used to prevent and treat venous thromboembolism (VTE). Though it has been the drug of choice for many advanced medical and surgical procedures with a long history, the adverse events, such as bleeding, heparin-induced thrombocytopenia (HIT), allergic reactions, follow. Therefore, low molecular weight heparins (LMWHs) and ultra low molecular weight heparins (ULMWHs), with lower molecular weights, higher anti-FXa activity, longer half-life times and lower incidence of adverse events than unfractionated heparin (UFH), were researched and developed. Fondaparinux, a chemically synthesized ULMWH of pentasaccharide, has the same antithrombin III (AT-III)-binding sequence as found in UFH and LMWH. In addition, AVE5026 and RO-14, another two ULMWHs, are obtained by selective chemical depolymerization. In this paper, we review the preparation process, pharmacological effects and clinical applications of fondaparinux, AVE5026 and RO-14.


Trademark
Hebei Changshan Biochemical Pharmaceutical Co. | Date: 2011-09-27

Chemico-pharmaceutical preparations for the treatment of cardiovascular and cerebrovascular diseases, thrombus; gelatin (e) for medical purposes, namely, gelatin capsules sold empty for pharmaceuticals; raw material medicine, namely, heparin sodium; biomedicine, namely, heparin sodium; dietetic food adapted for medical purposes; dietetic substances adapted for medical purposes, namely, beverages, sugars; nutritive substances for microorganisms for medical purposes; injections, namely, heparin sodium; tablets, namely, drug delivery agents in the form of tablets that provide controlled release of the active ingredients for a wide variety of pharmaceuticals; drugs for medical purposes, namely, for the treatment of cardiovascular and cerebrovascular diseases, thrombus.

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