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??OBJECTIVE To study the monthly dynamics of physical and chemical indexes in Achyranthis Bidentatae Radix(ABR, the dried root of Achyranthes bidentata Bl.) stored in simple and cool warehouses. METHODS ABR was stored in simple and cool warehouses for 27 months. The color was observed. The water content was determined based on the drying method. The contents of ??-ecdysone and 5-hydroxymethylfurfural (5-HMF) were determined by HPLC method. The accumulation of temperature difference between the simple and cool warehouses was evaluated with a relative temperature cumulation (RTC) method. The monthly dynamics of physical and chemical indexes of ABR was analyzed with RTC. RESULTS As the extension of storage time, the ABR stored in the simple warehouse showed deeper color and harder texture, but the ABR stored in the cool warehouse still had soft texture without significant color change. The contents of ??-ecdysone in ABR stored in the two warehouses both gradually decreased and dropped to lower than the limit of 0.030% ruled by China Pharmacopoeia when being stored for up to 27 months. The contents of 5-HMF of ABR stored in the two warehouses both increased and were higher for the sample in the simple warehouse than that in the cool warehouse. CONCLUSION The concept of RTC is put forward and used to study the monthly dynamics of chemical constituents in traditional Chinese medicine during storage for the first time. The physical and chemical indexes of ABR varies during storage. Two years of storage time of ABR is suggested.     

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??Chrysanthemum morifolium has a long history of culture and use in China. Due to different germplasm resources, producing areas, and processing methods, many cultivated varieties have formed now. The varieties and processing methods of C. morifolium are affected by economic interests and processing cost, which change gradually. On the basis of spot investigation and related literature study, the changes of the varieties and processing methods of C. morifolium were summarized in this paper. It will provide theoretical evidence for the culture, processing, quality evaluation, and clinical application of C. morifolium.     

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??OBJECTIVE To validate the conventional gel filtration chromatography (GFC) method for determination of the polymer impurities in ??-lactam antibiotics and achieve combination of GFC and RP-HPLC system. METHODS The effectiveness of the conventional GFC method was identified by 2D-GFC??LC-TOFMS and the polymer impurities found by GFC were identified by RP-HPLC. RESULTS The polymer impurities found by GFC mainly were degradation impurities and open ??-lactam ring impurities, which could not effectively characterize the sensitizing polymer impurities in cefotiam hydrochloride. CONCLUSION An effective method to characterize the polymer impurities in ??-lactam antibiotics may be established on the basis of online column switching technique which effectively combines the advantages of GFC and the ability of RP-HPLC to identify the special impurities.     

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??OBJECTIVE To prepare palmatine- loaded flexible nano-liposomes (PFNL) and study their pharmaceutical properties, in order to lay the foundation for the industral application. METHODS The flexible nano-liposomes were prepared by thin-film homogenization method with propyleneglycol (PG) as softening agent. The entrapment rate of palmatine was evaluated by protamine aggregation method and HPLC. The effects of concentrations of phosphatidylcholine (PSC), cholesterol (CH), and PG on the entrapment efficiency of palmatine were also investigated. The pharmaceutical properties of PFNL were evaluated by TEM, PCS and CLSM. The deformation of PFNL was determined by its relative rate of permeating the microporous filter membrane. The coagulation rate constant (K) was measured by constant temperature conductivity method. The side-by-side diffusion cells and pig vaginal mucosa were used to investigate the characteristics of the release of palmatine from PFNL in vitro, and the effects of PFNL on the expression of cytokines (SLPI, LF and SP-D) were investigated and compared with classic liposomes and lotion of palmatine. RESULTS The palmatine entrapment efficiency was (78??2.13)% when the PFNL were prepared with PSC (3%), CH (0.02%), and PG (20%). The prepared nano flexible liposomes had a closed spherical or elliptical shape and appeared as multi-lamellar vesicles under the TEM and CLSM.The calculated mean size was (185??19) nm, and the Zeta potential was (-53??2.27) mV. The deformation of PFNL was (79??5.75)%. The coagulation rate constant (K) of PFNL was always lower than that of traditional palmatine- loaded liposomes. The accumulated permeation amount of palmatine from the PFNL at 6.0 h was 1.53 and 2.86 folds of those of classic liposomes and lotion, respectively. Moreover, the expressions of cytokines (SLPI, LF and SP-D) in female SD rats after being treated with PFNL, PCL and PL were similar to that of the control group. CONCLUSION The prepared PFNL have high encapsulation efficiency, good stability and safety, and greatly increase the vaginal mucosa permeability of palmatine. Flexible nano-liposomes may be a useful drug delivery carrier for the gynecological application of palmatine.     

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??OBJECTIVE To study the chemical constituents and their proliferation activity on rat osteoblasts of Semen Sojae Praeparatum. METHODS The compounds were isolated by chromatography on silica gel column,MCI and sephadex LH-20 column. Their structures were elucidated by spectral analysis. The proliferation test was performed by using rat osteoblasts with MTT assays in vitro. RESULTS Twelve compounds were obtained and identified as daidzin(1), daidzein(2),genistein(3), genistin(4), glycitein(5), glycitin(6),apigenin(7), ??-sitosterol(8), stigmasterol(9), campesterol(10), syringaldehyde(11), syringic acid(12), respectively. CONCLUSION Compounds 5-11 are isolated from Semen Sojae Praeparatum for the first time. The five isoflavones show proliferation activity on rat osteoblasts, and aglycones proved to show better activity than glycosides.
     

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??OBJECTIVE To compare the setting methods for biologics data protection period between America and Japan, in order to provide suggestions for China. METHODS We made a contrastive study of American ??break even?? model and Japanese ??risk management evaluation?? model by using method introduction and characteristic analysis. RESULTS The two setting methods in the US and Japan focus on different system objectives, respectively. The Chinese choice of setting method needs to combine the feasibility of setting methods and the national conditions and policy goals for comprehensive consideration. CONCLUSION At present and the future for a long time, China's pharmaceutical industry is still in the ??imitation to innovation?? stage, and drug safety issues remain the core task. Therefore, the period of biologics data protection should be rationally set up by using ??risk management evaluation?? model as the base, ??break even?? model as supplement, so as to bring the three policy effects such as innovation incentive, the improvement of innovative drugs availability and strengthening the drug post-market safety monitoring.     

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??OBJECTIVE To explore the effects of Dracocephalum total flavonoids(TFDM) on myocardial ischemia/reperfusion injury(MIRI)induced autophagy in rat. METHODS In vivo MIRI model was established with ischemia 30 min and reperfusion 120 min, by ligation of left anterior descending coronary artery. TFDM(30 mg??kg^-1??d^-1) and autophagy activator(1 mg??kg^-1??d^-1) or inhibitor(25 mg??kg^-1??d^-1) pretreatment was given before making the model. The MIRI-induced infarct size, the activities of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK-MB) in plasma and apoptosis protein caspase-3 in tissue and the expression level of autophagy-related proteins LC3, Beclin-1 were observed. RESULTS Compared with model group, the experiment revealed that autophagy inhibitor alleviated MIRI-induced myocardial damage by decreasing the infarct size, myocardial enzyme LDH and CK-MB leak; and reducing apoptosis protein caspase-3 activity level. In addition, TFDM pretreatment significantly inhibited the expression of autophagy-related proteins LC3 and Beclin-1. CONCLUSION TFDM shows inhibitory effects on MIRI-induced autophagy,which may play an important role in the protection against MIRI.     

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??OBJECTIVE To study the chemical constituents of Swertia binchuanensis. METHODS The constituents were isolated and purified by column chromatography of silica gel. Their structures were identified on the basis of spectral analysis and chemical properties. RESULTS Five compounds are isolated and identified as 7-O-????-L-rhamnopyranosyl-(1??2)-??-D-xylopyranosyl??-1,8-dihydroxy-3-methoxyxanthone(1), 3-O-??-D-glucopyranosyl-1,8-dihydroxyl-5-methoxyxanthone(2), 7-O-??-D- glucopyranosyl-1,8-dihydroxyl-3-methoxyxanthone(3), amarogentin(4), and amaroswerin(5). CONCLUSION All of the compounds were isolated from S.binchuanensis for the first time.     

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??OBJECTIVE To investigate the chemical constituents in flowers of Paulownia fortunei (Seem.) Hemsl. METHODS The flowers of Paulownia fortunei (Seem.) Hemsl. were extracted with 50% aqueous acetone by tissue disruption extraction. The compounds were isolated and purified by Diaion HP-20, Toyopearl HW-40, Sephadex LH-20, MCI Gel CHP-20, silica gel column chromatography and preparative HPLC, and their structures were elucidated on the basis of spectral data and physiochemical properties. RESULTS Nineteen compounds were elucidated as 2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol(1), 1-phenylpropane-1,2,3-triol(2), 3,4-dihydroxy-β-methoxyphenethy alcohol(3), chryseriol(4), phenylpropanoid(5), apigenin(6), luteolin(7), 4-hydroxy-3-methoxybenzoic acid(8), 2-(4-hydroxyphenyl) ethanol(9), 3,4-dihydroxyphenylethyl alcohol(10), vanillic acid(11), 3-(4-hydroxy-3,5-dimethoxyphenyl) propane-1,2-diol(12), p-hydroxybenzoic acid(13), astragalin(14), nicotinic acid(15), thymidine(16), thymine(17), 5-(4′-hydroxybenzyl) hydantoin(18) and 1-(3-indolyl)-2,3-dihydroxypropan-1-one(19). CONCLUSION Compounds 1-3, 5, 8-10, 12, 14-19 are isolated from this plant for the first time.     

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??OBJECTIVE To establish a method for isomer analysis of bepotastine besilate eye drops and test the stability of isomer in the preparation. METHODS The analysis was performed on an ULTRON ES-CD chiral column (6.0 mm??150 mm,5 ??m). The mobile phase was 0.02 mol??L^-1 potassium phosphate monobasic-acetonitrile(75??25) at the flow of 0.8 mL??min^-1. The column temperature was maintained at 35 ?? and the detection wavelength was set at 225 nm. The injection volume was 10 ??L. RESULTS The limit of detection and limit of quantification of bepotastine besilate R-isomer were 12 and 48 ng, respectively. The linear range of bepotastine besilate R-isomer was 0.01-0.1 mg??mL^-1 and the repeatability was good at high, medium and low concentrations. CONCLUSION The method is simple and accurate, which can be used for isomer separation of bepotastine besilate and testing the stability of isomer in bepotastine besilate eye drops.     

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??OBJECTIVE To explore the statistical METHODS for proficiency testing in the drug control field. METHODS The statistical METHODS were sorted out with data processing used in inter-laboratory and proficiency testing by various industries both at home and abroad.The Grubbs test and Dixon test in classical statistical method were focused on as well as quartile method and iterative method in the robust statistical method, and the characteristics of the different statistic METHODS was summarized respectively.RESULTS Every method has its advantages and application conditions.CONCLUSION It is suggested that proper statistical method be chosen according to the data characteristics of the test RESULTS.     

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??In order to ensure the safety and effectiveness of biotech drugs, the CFDA has released a series of regulations and guidelines, and the NIFDC established an effective quality control technology system for recombinant drugs. This paper briefly reviews the important development stage of pharmaceutical biotechnology and the research and development situation of recombinant drugs in China, introduces in detail the establishment and application situation of the quality control technology system for recombinant drugs in the last 30 years in China, including the research basis and regulatory requirements for the quality standard, the quality standards of recombinant drugs in Chinese Pharmacopoeia Part ?? and the quality control requirements for recombinant drugs in the current Pharmacopoeia, the support of national science and technology projects for establishing quality control system of biotechnology drugs by NIFDC and the establishment and application of the recombinant drug quality standards and all kinds of test methods such as the determination of biological activity and protein content, physical and chemical analysis and protein structural identification, determination of purity and impurity since 1986; development of national standards for biological activity and content determination, establishment and validation of the quality standards of the physical and chemical reference substances used for peptide mapping analysis and isoelectric point determination of recombinant drugs; analysis of inspection reports of a total of 5 920 batches of biotech drugs for all kinds of tests including registration inspection, import inspection, sample inspection, commission, and contracts tests completed by Division of Recombinant Biological Products, IBPC, and NIFDC since 2001.     

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??OBJECTIVE To investigate the chemical constituents in the roots of Allium tuberosum. METHODS Colum chromatography with different materials such as silica gel was used to isolate and purify the chemical constituents. Their structures were identified by spectroscopic analysis. RESULTS Nine compounds were isolated from the roots of Allium tuberosum and their structures were identified as 4,8-dihydroxyacetophenone-8-O-ferulate(1), 4,8-dihydroxyacetophenone(2), 3,4,5-trimethoxybenzoic acid(3), 3,4,5-trimethoxycinnamic acid(4), buddlenol D(5), E-1,6,11-triene-4,5,9-trithiadodeca-9,9-dioxide(6), tianshic acid(7), daucosterol(8), and linoleic acid(9). CONCLUSION Compound 1 is a new compound and compounds 2-5 are obtained from Allium tuberosum for the first time.     

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??OBJECTIVE To put forward some suggestions on drug manufacturing site changes for our country. METHODS By studying American regulations of drug manufacturing site changes, analyze its advantages in regulations. RESULTS AND CONCLUSION It??s suggested that We should apply the risk-based approach to classify drug manufacturing site changes, focus more on high-risk manufacturing site change to lighten the burden of the agency and corporations, and liberalize drug manufacturing site changes to promote smooth implementation of the marketing authorization system.     

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??OBJECTIVE To prepare crossed-linked sodium hyaluronate (CHA) gel and study its rheological property. METHODS CHA was prepared using 1,4-butanediol diglycidyl ether (BDDE). The linear viscoelastic properties and creep recovery of hyalouronan(HA) and CHA were measured with a rheometer. The influencing factors of rheological properties were analyzed, such as concentration, proportion of cross-linker and temperature. RESULTS Cross-linked sodium hyaluronate gel was prepared. The viscoelasticity was measured with a pair of 20 mm stainless steel plates at the frequency of 1 Hz and shear-strain of 1 Pa at (25??0.1)??. As shown by the creep recovery test, CHA had a smaller strain and shorter time to recover to the minimum strain than HA, which showed typical linear viscoelastic and creep recovery properties. CONCLUSION CHA is a non-Newtonian fluid, which is easy to administer and conforms completely to the requirements for viscoelastic supplementation materials for intra-articular injection. Compared with HA, CHA has more advantageous viscoelastic property and stability.