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Wang Y.,Institute of Microbiology | Wang Y.,University of Chinese Academy of Sciences | Zheng Z.,North China Pharmaceutical Group Corporation | Liu S.,Institute of Microbiology | And 4 more authors.
Journal of Natural Products | Year: 2010

Six new polyketides including four oxepinochromenones, conioxepinols A-D (1-4), one furochromenone, coniofurol A (5), and one xanthone, conioxanthone A (6), have been isolated from the crude extract of the endolichenic fungus Coniochaeta sp. The absolute configurations of C-7 in 1 and the 7,8-diol moiety in 3 were assigned using the modified Mosher's and Snatzke's method, respectively, whereas that of C-8 in 5 was deduced via the circular dichroism data of the [Rh2(OCOCF3)4] complex. Compounds 2-4 showed modest cytotoxicity against a small panel of human tumor cell lines. © 2010 The American Chemical Society and American Society of Pharmacognosy. Source


Fan H.,Beijing University of Technology | Peng Y.,Beijing University of Technology | Li Z.,Changchun Gold Research Institute | Chen P.,North China Pharmaceutical Group Corporation | And 2 more authors.
Journal of Polymer Research | Year: 2013

Hydrophobic symmetric flat-sheet membranes of polyvinylidene fluoride (PVDF) for use in vacuum membrane distillation (VMD) were successfully fabricated by the vapor-induced phase separation (VIPS) method using the double-layer casting process. To avoid the delamination that often occurs in double-layered membranes, the same PVDF polymer was employed in both the upper layer and support layer casting solutions. Solutions with low and high PVDF contents were co-cast as the upper layer and support layer of the membrane that was formed. In the VIPS process, the low PVDF content solution favored the formation of a layer with a porous and hydrophobic surface, whereas the solution with a high PVDF concentration favored the formation of a layer with high mechanical strength. The effect of the vapor-induced time on the morphological properties of the membranes was studied. As the vapor-induced time was increased, the cross-section of the membrane changed from an asymmetrical finger-like structure to a symmetrical sponge-like structure, and the surface of the membrane became rough and porous. The membrane subjected to the longer vapor-induced time also exhibited a higher permeating flux during the VMD process. The best PVDF membrane fabricated in this study had a mean radial pore size of 0.49 μm, and the rough upper surface produced a static contact angle of 145 with water. During the VMD process with a 3.5 wt.% sodium chloride (NaCl) aqueous solution, the best membrane that was fabricated produced a permeating flux of 22.4 kg m-2 h-1 and an NaCl rejection rate of 99.9 % at a feed temperature of 73 C and a downstream pressure of 31.5 kPa. This performance is comparable to or superior to the performances of most of the flat-sheet PVDF membranes reported in the literature and a polytetrafluoroethylene membrane used in this study. © 2013 Springer Science+Business Media Dordrecht. Source


Simone E.,Loughborough University | Zhang W.,North China Pharmaceutical Group Corporation | Zhang W.,Purdue University | Nagy Z.K.,Loughborough University | Nagy Z.K.,Purdue University
Crystal Growth and Design | Year: 2015

Purity is a critical quality attribute for both pharmaceutical and biopharmaceutical products. The presence of impurities (solvents, salts, or byproducts of the synthetic path) in drugs can cause a reduction of their effectiveness or can even be toxic for the patients. Biopharmaceuticals are produced by biological processes which are difficult to control. Therefore, the amount of impurities that has to be removed can be significantly higher than in the case of synthetic pharmaceuticals. The aim of this work is to exploit process analytical technology tools and different feedback control strategies (T-control, direct nucleation control, and supersaturation control) for the crystallization of a biopharmaceutical product. UV/vis spectroscopy and focused beam reflectance measurement combined with a Crystallization Process Informatics System (CryPRINS) were used to improve the crystal size distribution and purity of crystallized vitamin B12. The different feedback control strategies were compared to classical crystallization techniques in terms of purity of the final crystal and quality of the crystal size distribution, and it is shown that using suitable crystallization feedback control strategies, the purity and quality of crystals can be improved. © 2015 American Chemical Society. Source


Liu B.-N.,North China Pharmaceutical Group Corporation
Chinese Journal of Biologicals | Year: 2014

Objective: To develop a large-scale perfusion culture process of CHO-C28 cells in fixed bed reactor for preparation of recombinant hepatitis B surface antigen (HBsAg). Methods: The feasibility of perfusion culture of CHO-C28 cells in fixed bed reactor was investigated by mock culture in prepared mini-bioreactor in which medium flew through the surface of carriers in an axial rotation mode, based on which a bench-scale suspension culture process of CHO-C28 cells was developed by using AP20 fixed bed reactor. The 2.3 × 1010 cells after digestion in AP20 reactor were collected and inoculated to AP200 fixed bed reactor to develop a pilot process The culture liquids were harvested and determined for dissolved oxygen, pH value as well as glucose, lactic acid and HBsAg concentrations, and the results were compared with those of culture in rolling bottle. Results: CHO-C28 cells inoculated into mini-bioreactor with no-woven paper could be cultured continuously by perfusion for 60 d, in which the expression level of HBsAg was 1 100 ng/ml. However, the expression level in CHO-C28 cells in AP20 reactor was about 1 100 ng/ml in maintain period. A portion of 2.3 × 1010 CHO-C28 cells were harvested on day 10 after culture in AP20 reactor, and was cultured continuously by perfusion for 60 d, during which the glucose consumption rate reached 450 g/d at most in growth period and decreased to 250 g/d in maintain period. In the whole maintain period, the glucose concentration was about 1.5 g/L, while the lactic acid accumulation in harvest was 22 mmol/L, and the expression level of HBsAg was about 1 200 ng/ml. The technological condition of perfusion culture process in fixed bed reactor was controlled precisely, while the culture environment was more suitable for the growth of CHO-C28 cells, and the culture cycle was equivalent to that of culture in rolling bottle. Conclusion: The expression level of HBsAg of in CHO-C28 cells cultured by perfusion culture process in fixed bed was equivalent to that by rolling bottle culture, which was suitable for large-scale production. Source


Ma C.,CAS Institute of Microbiology | Ma C.,University of Chinese Academy of Sciences | Li Y.,CAS Institute of Microbiology | Li Y.,University of Chinese Academy of Sciences | And 5 more authors.
Journal of Natural Products | Year: 2011

New N-hydroxypyridones, militarinones E (1) and F (2), phenylhydrazones, farylhydrazones A (3) and B (4), a quinazolinone, 2-(4-hydroxybenzyl)quinazolin- 4(3H)-one (5), and the known militarinones A (6) and B (7) were isolated from cultures of the Cordyceps-colonizing fungus Isaria farinosa. The structures of 1-5 were elucidated by spectroscopic methods, and 3 was confirmed by X-ray crystallography. The absolute configuration of the C-4' secondary alcohol in 1 was deduced via the circular dichroism data of the in situ formed [Rh 2(OCOCF3)4] complex. Compounds 1 and 6 showed significant cytotoxicity against A549 cells, whereas 7 was active against Staphylococcus aureus, Streptococcus pneumoniae, and Candida albicans. © 2011 American Chemical Society and American Society of Pharmacognosy. Source

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