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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  • 2017 Volume 48 Issue 06
    Published: 10 June 2017
      

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  • BI Xingjian1, HONG Qiyang2, YU Hai1*, LI Shaowei1,2, XIA Ningshao1,2
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Due to precise specificities and low side-effects, therapeutic antibodies are becoming more and more important in the biotechnology industry. With promising application prospects in clinical practice, therapeutic antibodies are expected to treat diseases like cancers, autoimmune diseases, cardiovascular diseases, diabetes, Alzheimer’s diseases and so on. Antibody-based molecular design and targeted therapy is the fastest growing field of biomedical industry in recent years. However, there are still challenges for the development and production process of therapeutic antibodies. Among these challenges, antibody aggregation is one of the key determinants for antibody. Screening and rational design of potent antibody candidates without obvious aggregation propensity are critical in the earlier stage of antibody development. Comparing to conventional methods, in silico prediction of protein aggregation can provide key information on the stability and solubility of the antibody drugs and hence greatly improve the efficiency of drug development.
    Here, we summarize the approaches into sequence-based method and structure-based method. The former makes predictions from amino acid sequence only, while the latter approaches predict aggregation by calculating interactions on structures model. Furthermore, we illustrate their principles and prospects in therapeutic antibodies development which might provide paradigmatic reference for computation-based antibody design in the future. Depending on the different advantages of these approaches, a right choice could be potentially useful in the rational design of therapeutic candidates with not only high potency and specificity but also improved stability and solubility.
  • ZHAO Liyan, YANG Yanmei, KOU Na, ZHANG Wanming*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Pluronic P123 (P123) is one of the most common representatives of poloxamer polymers and has many advantages in delivering drugs, such as increasing the solubility of hydrophobic drugs, extending the circulation time in vivo, enhancing cellular uptake, blocking tumor cell migration, reversing multidrug resistance and enhancing the therapeutic effect of antitumor drugs. Through structural modification of the terminal hydroxyl group of P123, novel materials are obtained by forming ester bond, amide bond, glycosidic bond, and so on. These materials can be used for preparing the micelles of poloxamer-drug conjugates, ligand-mediated active-targeting and other drug delivery systems to deliver drugs or therapeutic genes to the target sites. The applications of modified P123 polymer to drug delivery are reviewed in this paper.
  • SHI Yalei1, LI Yang2, ZHOU Junpeng1, WU Jiang1, ZHU Jintao1*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A novel synthetic process of Ketoprofen was reported. 1-(4-Nitrophenyl)propan-1-one (2)reacted with glycol via ketalation to give 2-ethyl-2-(4-nitrophenyl)-1,3-dioxolane (3), after cyclization with benzyl cyanide followed by reduction and ring-opening reaction in the presence of Fe/HCl, a new compound 1-(4-amino-3-
    benzoylphenyl)propan-1-one (4) which had not yet been reported in literature was obtained. Then 4 was subjected to diazotization deamination and bromination to afford 1-(3-benzoylphenyl)-2-bromopropan-1-one (6). Compound 6 reacted with neopentyl glycol via ketalation followed by rearrangement in the presence of potassium acetate to give a reactive intermediate, and then the latter was subjected to hydrolysis to prepare ketoprofen with an overall yield of 40%(based on 2). This new process has some advantages, such as mild reaction conditions and simple operation, which are more suitable for industrial production.
  • ZHAO Lizhi, LIU Yankui, WANG Zengxue, ZHANG Guimin
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    A new approach to selectively monoacetylate cyclopropane-1,1-dimethanol (2) was reported. 2 reacted with 2-bromo-1,1-dimethoxyethane via acetal exchange to give 6-bromomethyl-5,7-dioxaspiro[2.5]octane (4),after dehydrobromination, an unisolated intermediate cyclic ketene acetal was obtained, then the latter was subjected to hydrolysis in hydrobromic acid aqueous solution to afford [1-(bromomethyl)cyclopropyl]methyl acetate (5).This method could efficiently convert compound 2 to the corresponding monoacetylated diol. Then 5 was subjected to substitution and hydrolysis to give 1-(hydroxymethyl)cyclopropyl acetonitrile (7), which was followed by bromization,substitution, hydrolysis and acidification to provide [1-(mercaptomethyl)cyclopropyl]acetic acid(1) with an overall yield of 58% .
  • WANG Jiansong, XI Long, YE Weiwen, XING Sheng
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    Plackett-Burman combined with Box-Behnken response surface methodology was used to optimize the formulation of sustained-release layer of enalapril maleate and felodipine double-layer tablets. Plackett-Burman design was adopted to screen the major influential factors of the release of felodipine, then the selected factors were further investigated by Box-Behnken response surface methodology. The multiple linear regression and second-order quadratic models were established to predict the best formulation. The statistical data showed that hypromellose (HPMCK4M), lactose and polyoxyl 40 hydrogenated castor oil had significant influences on the release of felodipine. The results of the significant analysis in Box-Behnken design was similar to that in Plackett-Burman design. Lactose and polyoxyl 40 hydrogenated castor oil had positive effects on the release of felodipine at 1, 4 and 7 h, in the opposite, HPMC had
    a negative effect. The optimized formulation was achieved with HPMC of 55 mg, lactose of 96 mg, and polyoxyl 40 hydrogenated castor oil of 1 mg, the release profiles of felodipine from the home-made tablets were similar to those of the reference preparation (Lexxel®) in different release media. The method for optimizing the formulation was simple with good predictability, and its results met the requirements.
  • HAO Guizhou, GUAN Yuanyuan, ZHANG Guimin*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The celecoxib ethosomes were prepared by ethanol injection method and the entrapment efficiency was detemined by ultracentrifugation. The formulation of the ethosomes was optimized by orthogonal design with entrapment efficiency as the index. The morphology of the optimal ethosomes was observed by transmission electron microscopy (TEM), and the partical size and ζ potential were conducted with the help of dynamic light scattering. The results showed that the optimal product had a spherical shape with the mean entrapment efficiency of (72.56±0.29)%.The average partical size, polydispersity index and ζ potential were (189.4±0.8)nm, 0.322±0.012 and (-21.58±0.26)mV,respectively. Then, the gels based on the optimal ethosomes and the bulk drug were prepared with Carbopor 934 as a gel matrix. The in vitro transdermal test were carried out with excised mouse skin as the barriers to compare the permeation amount and skin retention of the above two gels. The results showed that the steady penetration rates of celecoxib ethosomal gel and celecoxib gel were (17.89±0.18) and (7.62±0.12)μg·cm-2·h-1, while the retention amounts at 12 h were (13.62±0.17) and (5.69±0.25)μg/cm2. It indicated that the celecoxib ethosomal gel might to be a promising carrier of transdermal delivery for celecoxib because of the significant increasing in both the permeation rate and skin retention.
     
  • FENG Yunhua, PAN Yanting, LIANG Yongkun*
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    To solve the problem of methyl salicylate content decrease in camphor, menthol and methyl salicylate cream during the shelf life, the amounts of glyceryl stearate PEG-75 (Gelot 64) and carbomer (Carbopol 980) and the ratio of butylated hydroxytoluene (BHT) to edetate disodium were optimized by orthogonal design with appearance, viscosity of the cream and content decline of methyl salicylate as the indexes. The accelerated stability of the optimal product was investigated with appearance, delamination, contents and related substances as the indexes. The results showed that the optimal formulation should contain 12 g of Gelot 64, 7.5 g of mono- and di-stearin, 0.02 g of BHT, 0.8 g of Carbopol 980, 1 g of triethanolamine, 0.02 g of edetate disodium and 0.1 g of ethylparaben per 100 g of the cream.Compared with the original product, the improved cream was more smooth and the content of methyl salicylate were more stable.
  • MIAO Tianyao1,2, ZHAO Jingdan2, LIU Hao2*
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    An HPLC method was established for the detection of the related substances in sirolimus, so as to provide a new reference for its quality control. A Kromasil 100-5 C18 column was used, with the mobile phase A of 20 mmol/L ammonium formate solution (adjusted to pH 3.8±0.05 with formic acid), and mobile phase B of acetonitrile (containing 1% methyl tert-butyl ether) for linear gradient elution, at the detection wavelength of 277 nm. This method was suitable for the simultaneous control of sirolimus open-loop degradation impurities and the process impurities, and can improve the separathion between process impurities prolyl sirolimus and demethyl sirolimus peaks, as well as the seperation of demethyl sirolimus and sirolimus peaks. It was linear for sirolimus in the range of 0.5—50 μg/ml, with the limit of detection (LOD) and the limit of quantification (LOQ) of 0.2 and 0.5 μg/ml. This method was specific, accurate
    and sensitive, it can be qualified for the quality control of sirolimus.
  • ZHANG Yanyan1, HAN Guangming1, LI Weigang1, LUO Zhaoliang2
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    An HPLC method for the simultaneous determination of six furocoumarine components including psoralen, 8-methoxypsoralen, isopsoralen, 5-methoxypsoralen, imperator and trimethylpsorale in the Psoralea corylifolia Linn. from different habitats. A Capcell Pak-C18 column was used, with the mobile phase of methanol∶water for gradient elution, at the detection wavelength of 248 nm. The calibration curves were linear for the six components in the range of 1—100 μg/ml. Their average recoveries were 97.2%, 99.5%, 96.8%, 99.2%, 99.6% and 98.7%, with RSDs of 1.54%,1.35%, 0.65%, 0.43%, 0.18% and 0.26%, respectively. Contents of the six components in Psoralea corylifolia Linn. from ten different habitats were 0.21%—0.86%, 0.10%—0.17%, 0.28%—0.89%, 0.14%—0.43%, 0.10%—0.21% and 0.10%—0.26%, respectively. The methodology validation proved that the reported method was applicable for the quality control of Psoralea corylifolia L..
  • CHEN Yanping1, ZHANG Xinyun1, SHI Xiaoye1, PAN Ying1, CHEN Guiliang2
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The rheological curve, yield value and thixotropy of povidone K30 were measured, and the effect of temperature on the rheological properties of the samples were investigated by the rheometer. It was determined to be (25±0.1) ℃ for the measurement of povidone K30 viscosity by the rheometer, and the corresponding shear stress was 0.2 Pa. The dynamic viscosities of the sample solution and water were measured. The relative viscosity and K value of the
    samples were calculated. This method was simple, rapid and accurate, with wide applicability and good reproducibility.Compared with the traditional Ubbelohde capillary viscometer method, the temperature control system of the rheometerin this method can quickly and accurately control the sample to the predetermined temperature, with the accuracy of 0.01 ℃. In addition, all procedures can be automatically completed except the preparation and addition of the samples. It contributes to reducing the experimental error caused by manual operation and artificial judgment.
  • DENG Yuanyuan1, QI Qunfu2, SHEN Jingxia3
    Abstract ( ) Download PDF ( )   Knowledge map   Save
    The new version of the GMP standard on clean made different previous requirements, but it did not provide quantitative data. In practice, it mainly reflected in the inability to reasonably determine the air supply, resulting in no consensus of opinions on projects. According to a large number of engineering field testing and debugging results, a reasonable amount of air supply was derived, and its reliability was verified through the CFD simulation.
  • YUE Zhihua, LI Huiyi
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    Children are at exceptionally high risk for adverse drug events because of physiological immaturity,lack of testing and information on medications, availability of appropriate medication formulations and strengths. It’s very important to carry out the surveillance study on the safety of pediatric drugs. In this study, the regulations and reported data of children's medication safety monitoring in China and the United States are analyzed, hope to provide reference for domestic children's drug safety monitoring research and promote rational use of drugs for children.
    Key Words:
  • CHANG Feng, JI Meiyan, ZHANG Jianyun
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    By comparing the characteristics and effect of medical insurance payment methods of inpatient and outpatient in foreign countries, this article aims to direct domestic payment methods reform of medical insurance.The study have showed that diagnosis related groups (DRGs) has been implemented universally in hospitals of foreign countries but drug costs are not included in outpatient payment. Our medical insurance payment reform should be carried on gradually from global budget to a single DRGs, then transition to mature DRGs payment. Global budget is the best choice currently. The key problem is to control the total amount of medical services and drug costs.