���߶�ά����ɫ�׷���Һ��ɫ��-����ʱ�����׼���������ͷ���氲�оۺ������ʵķ����о�

??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.     

������-��������԰�����������ƺϳɼ������л�о�

??OBJECTIVE To design and synthesize brain targeting danshensu (DSS) derivatives and study their metabolism in rat plasma and brain homogenate in vitro. METHODS Tetramethylpyrazine and its derivatives were selected as carriers to design the brain targeting danshen suderivatives. Lipid-water partition coefficient (logP), brain blood concentration ratio (BB), and P-glycoprotein affinity of the derivatives were predicted by some calculation softwares and the better compound DT3 was chosen for the next synthesis. The degradation of DT3 and its intermediate DT1 in rat plasma and brain homogenate were measured by HPLC-UV. RESULTS Two danshensu-pyrazine ester derivatives were synthesized, ie DT1 and DT3. A simultaneous determination method of DT3, DT1, and (3,5,6-trimethylpyrazine-2-yl)methanol (TMPM) in rat plasma and brain homogenate was established. The degradation of DT3 in rat plasma and brain homogenate underwent the following processDT3??DT1??the active metabolites of DSS and TMPM.Compared with DT1, the degradation of DT3 in rat plasma slowed down.The half-lives (t_1/2) of TMPM were 1.68 and 1.71 min, respectively. Also,DT3 could quickly release the active metabolitein rat brain homogenate, and the concentration of TMPM showed a steady increase with a t_1/2 of 222.88 min. CONCLUSION The danshensu-pyrazine ester derivative DT3 has an extended t_1/2 in rat plasma, and it can be degraded to active metabolite quickly in rat brain homogenate.     

16-����˫ϩ��ͪ֬����������⿹���������о�

??OBJECTIVE To investigate the antitumor effect of 16-dehydropregnenolone(16-DHP) liposomes. METHODS Twelve kinds of tumor cells were used to determine the cytotoxic effect of 16-DHP liposome by MTT assay. The established tumor xenograft in nude mouse model was used to evaluate anti-tumor effect of 16-DHP liposomes after tail vein injection. RESULTS IC₅₀ value of 16-DHP liposomes to the human hepatoma cell HepG2, human oral carcinoma KB cell, human breast cancer T47D, human gastric cancer cell SGC7901, human fibrosarcoma cell HT1080, human ovarian cancer cell SKOV3,human prostate cancer cell PC3, human prostrate cancer cell DU145, human lung cancer cell A549, human rhabdomyosarcoma A204 cell and human cervical carcinoma cell HeLa were 44.69, 9.17,26.22, 19.58, 28.01, 37.18, 24.58, 21.38, 54.69,4.18 and 8.96 ??g??mL^-1, respectively. The relative tumor increment rate and inhibition rates of tumor weight were 93.7%, 60.52%, 37.84% and 23.05%,48.84%,69.70% respectively after treated with 16-DHP liposomes (7.5, 15 and 30 mg??kg^-1??d^-1 , 28 d). CONCLUSION 16-DHP liposomes possess in vitro and in vivo anti-tumor activities.
     

�ʲ���-�Ǿ���ż����ĺϳɼ�����ϸ����ȡ�о�

??OBJECTIVE To prepare conjugate of low molecular weight chitosan(LMWC)with glycyrrhizin (GL) and investigate its cellular uptake by proximal tubular epithelial cells (HK-2). METHODS Glycyrrhizin-LMWC (GL-LMWC) conjugate was synthesized by the reaction between the amino group of LMWC and the active ester group of GL. Drug release was studied in phosphate buffer (pH 4.0) containing papain. The uptake of the conjugate by HK-2 cells and its intracellular distribution was studied with laser confocal microscopy. RESULTS The chemical structure of GL-LMWC conjugate was confirmed by IR and ¹H-NMR. The GL grafting rate was determined to be 29.3%. The drug liberation from the conjugates was significantly accelerated in the presence of papain, which confirmed the capability of the conjugate to degrade in lysosomes. The conjugate could be internalized by HK-2 cells. CONCLUSION The GL-LMWC conjugate with well-defined structure is successfully synthesized and exhibitts high cellular uptake efficiency. The conjugate has the potential to retaing GL in the kidney for a prolonged duration and to sustain its release locally for better efficacy.     

��-����������ѧ�����о�

??OBJECTIVE To investigate the rheological property of Kappa carrageenan and the effects of standing time, concentration, and temperature on the viscosity of carrageenan solution.METHODS The fluid type was determined by fitting the rheological profiles to Power law model.The effect of temperature on the rheological behavior was investigated according to the viscous flowactivation energy(E??) which was calculated by the Arrhenius formula. RESULTS The viscosity of carrageenan solution decreased with the increase of shear rate and temperature,whereas it increased with the concentration. There existed a positive correlation between E?? and concentration. Furthermore, the effects of different cations on the viscosity were also studied and the results indicated that the viscosity increased significantly with the ionic concentration, especially that of potassium chloride.CONCLUSION Carrageenan was inferred to be pseudo-plastic fluid which hasthe character of shear thinning effect and its viscosity is significantly affected by cationic species.     

����Է��������Ǿ���-�������װ���ż��������������ϵͳ���о�

??OBJECTIVE To synthesize low molecular weight chitosan-acetylcysteine (LMWC-NAC) conjugate and investigate its renal targeting profile and the rapeutic effects in model mice with acute kidney injury (AKI).METHODS NAC was conjugated to LMWC by EDC/NHS reaction and the LMWC-NAC conjugate was identified by ¹H-NMR. The cellular uptake of LMWC-NAC conjugate and megalin receptor involved in this process was investigated in vitro. In addition, the tissue distribution of ICG-labelled LMWC-NAC conjugate was investigated in nude mice. AKI were induced by LPS intraperitoneal injection (20 mg??kg^-1).The parameters including Scr, BUN, inflammatory factors (TNF-?? and IL-1??),and oxidative stress (MDA) were determined and renal histology was observed.RESULTS LMWC-NAC conjugate was successfully synthesized by the amide interaction.The in vitro studies demonstrated that the uptake of LMWC-NAC conjugate was mediated by the megalin receptor on HK-2 cells, and the tissue distribution experiment indicated that LMWC-NAC conjugate was mainly accumulated in the kidney.LMWC-NAC conjugate significantly suppressed Scr, BUN, inflammatory factors and oxidative stress (P<0.01) and improved kidney injury. CONCLUSION LMWC-NAC conjugate showed good renal targeting profile and effect in recovering renal functions, which indicates the potential of LMWC-NAC conjugate as a safe and efficient drug delivery system for the treatment of AKI.     

������-�Ǿ���˫���������Ƭ���ڽ᳦�������ҩ����о�

目的以壳聚糖为酶触型结肠靶向给药系统的材料,研制可用于结肠靶向的多单元口服给药系统(迷你片),以期为结肠部位疾病治疗的药物输送提供重要参考。方法以结肠癌的治疗药物-吲哚美辛为模型药物,首先制备固体分散体,再采用直接压片法和包衣技术制备尤特奇-壳聚糖双层包衣结肠靶向迷你片,考察靶向迷你片在不同释放介质中的释药行为,采用小动物活体荧光成像技术考察制剂在体内的转运和吸收情况,并以比格犬为动物模型进行药动学研究和生物利用度评价。结果制备的壳聚糖多单元结肠靶向迷你片可以完整形态通过大鼠胃和小肠,并靶向在结肠部位缓慢释放,比格犬体内药动学数据表明,自制结肠靶向迷你片的释药时间显著延长,血药浓度平稳。结论本实验制备尤特奇-壳聚糖双层包衣多单元迷你片给药系统具有较好的结肠靶向性和缓释效果,可为治疗结肠疾病的制剂开发提供重要参考。     

������֬����ȡ�ͦ�-���������Ϲ����о�

??OBJECTIVE To optimize the extraction and inclusion processes of ginger oleoresin from Zingiberis Rhizoma Recens. METHODS Supercritical carbon dioxide extraction was selected to extract ginger oleoresin from Zingiberis Rhizoma Recens. The extraction condition was optimized by orthogonal experiment. The inclusion method, the ratio of ginger oleoresin to ??-cyclodextrin and inclusion time were studied as factors of inclusion process. RESULTS The optimized extraction technology was as follows: extraction temperature was 50 ??, extraction pressure was 25 MPa, separation pressure was 9 MPa and extraction time was 90 min. The optimal inclusion method was triturating inclusion, with the ratio of ginger oleoresin to ??-cyclodextrin of 1??8 and inclusion time of 60 min. CONCLUSION The optimized technology of extraction and inclusion is stable and feasible, and can be used for the extraction and inclusion of ginger oleoresin.     

Һ��ɫ��-�������׷��ⶨȮѪ�����������������Ƶ�Ũ�ȼ��䶾������ѧ�о�

??OBJECTIVE To establish an LC-MS/MS method to determine (S)-pantoprazole sodium in dog plasma and investigate its toxicokinetics. METHODS After protein precipitation with acetonitrile, the analyte and internal standard were separated on CHIRALCEL OJ-RH column (4.6 mm ??150 mm, 5 ??m) with acetonitrile-water (28??72) as mobile phase eluted at a flow rate of 0.6 mL??min^-1. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The MRM transitions of m/z 384.0/199.8 and m/z 180.0/110.0 were used to quantify (S)-pantoprazole sodium and phenacetin, respectively. Beagle dogs were intravenously given (S)-pantoprazole sodium for 4 weeks at low, medium, and high dosages (10, 20, 40 mg??kg^-1??d^-1). RESULTS The calibration curve was linear over the concentration range of 50-30 000 ng??mL^-1. The RSDs were less than 15%, and the accuracy was in the range of 85%-115%. The AUC_{0-4 h} and ??_max of (S)-pantoprazole sodium were proportional to the dosages. CONCLUSION The established method can be applied to the determination of (S)-pantoprazole sodium in plasma of dogs and is suitable for the toxicokinetic study.     

�غ��������ش��Ծ�����-�ǻ����Ṳ�������������Ÿ�Ӧ�����յ�ҩ���ͷŵ��о�

??OBJECTIVE To prepare PLGA magnetic nanoparticles loaded with tetrandrine, heat the nanoparticles by inductive heating system, and study the particle size, morphology and drug release before and after heating. METHODS Co-loaded PLGA NPs were prepared by emulsion solvent diffusion method; the physicochemical and magnetic characteristics of co-loaded PLGA NPs were investigated by DLS, SEM, TEM and VSM; RP-HPLC and ICP-MS analysis were used to measure the tetrandrine and Fe₃O₄ loading and entrapment efficiency. The EASYHEAT system was applied to heat the nanoparticles and further investigate the changes of particle size, morphology and drug release after inductive heating. RESULTS Tetrandrine-loaded PLGA magnetic nanoparticles showed spherical shape with smooth surface and the Fe₃O₄ NPs were homogeneously distributed inside the polymeric nanoparticles; VSM result indicated that the co-loaded PLGA NPs were superparamagnetic; both tetrandrine and Fe₃O₄ showed good loading and entrapment efficiency. After being heated to 45 ??, the diameter of co-loaded PLGA NPs increased; the morphology changed from a spherical shape into a nondefined, irregular shape; arrangement or aggregation of the incorporated Fe₃O₄ NPs were found. In addition, the drug release amount was also increased. CONCLUSION With superparamagnetic property, the tetrandrine loaded-PLGA magnetic nanoparticles can effectively control the drug release behavior by inductive heating.
     

岩白菜素固体分散体渗透泵片制备工艺

目的:利用固体分散技术改善微溶性药物岩白菜素的体外溶出行为,进而考察片芯及包衣处方对岩白菜素固体分散体渗透泵片体外释药行为的影响,并优选最佳片芯及包衣处方。方法:采用熔融法制备岩白菜素固体分散体,并测定其溶出速率和溶解度;根据不同时间的累积释放度,考察药物的释放情况,通过单因素考察及正交试验设计优化片芯及包衣处方。结果:包衣膜中增塑剂的用量对岩白菜素固体分散体渗透泵片体外释药行为有影响。最后所得处方可在12 h内稳定释药且累积释放度可达到90%以上。结论:以岩白菜素固体分散体为中间体制成单室单层渗透泵片,其释药行为符合一级动力学过程。     

三七总皂苷渗透泵控释片的研制

目的:制备三七总皂苷渗透泵控释片。方法:考察各因素对药物释放的影响,采用正交试验优化处方。结果:包衣膜的增重和包衣液中PEG400用量对三七总皂苷渗透泵控释片的体外释药行为有显著影响,得到最佳处方为:衣膜增重5%,PEG400的用量为90%,NaCl的用量为30%。结论:通过处方优化可将三七总皂苷制成释药恒速、较完全的渗透泵控释片。     

黄杨宁渗透泵型控释片的设计及释放度的研究

目的:以黄杨宁为模型药物制备黄杨宁渗透泵控释片。方法:采用酸性染料染色分光光度法对其释放度进行测定,考察不同处方下药物的释放情况。结果:制备的黄杨宁渗透泵控释片体外释药速度较平稳。结论:本制剂在14 h内呈现良好的零级释药特征,此后随渗透泵内药量的减少,释放速度有所下降。     

三七总皂苷微孔渗透泵片释药机制

目的:研究三七总皂苷微孔渗透泵片的释药机制.方法:通过考察三七总皂苷微孔渗透泵片在不同渗透压介质中的释放行为及不同释放方法对药物释放速率的影响,探讨该制剂释放机制.结果:随着包衣膜内外渗透压差的增大,药物释放速率减缓;药物在水及pH6.8的磷酸盐缓冲液中释放行为相似,但在pH 1.0的盐酸溶液中释放速率降低;释放方法对药物释放速率无显著影响.结论:此片剂药物释放主要以渗透压梯度驱动机制为主,少量药物则直接扩散释药.     

非诺贝特双层渗透泵片在Beagle犬体内的药动学研究

目的 研究非诺贝特双层渗透泵片在犬体内的药动学特征,并评价受试制剂和参比制剂的生物等效性。方法 采用LC-MS测定比格犬体内的血药浓度,采用DAS 2.1.1软件计算药动学参数。结果 受试制剂和参比制剂血浆中非诺贝特酸的Cmax分别为（1 100.0±771.2）、（924.3±564.0）ng/mL,tmax分别为（6.7±8.5）、（2.5±0.5）h,AUC0-t分别为（17 841.1±12 220.7）、（17 615.5±12 870.2）ng·h/mL;t1/2分别为（17.7±8.2）、（16.4±3.3）h,MRT0-t分别为（24.7±4.0）、（24.5±5.2）h,受试制剂中非诺贝特酸的平均相对生物利用度为（104.7±12.4）%。结论 受试制剂非诺贝特渗透泵片和参比制剂非诺贝特缓释胶囊具有生物等效性。     

HPLC法测定复方丹参渗透泵型控释片中丹参酮ⅡA的含量

目的:建立以HPLC法测定复方丹参渗透泵型控释片中丹参酮ⅡA的含量的方法。方法:色谱柱为Hy-persil ODS C18柱(4.6mm×250mm,5μm),流动相为甲醇:水(85:15);流速为1.0mL.min-1;检测波长为270nm。结果:丹参酮IIA在1.6～14.4μg.mL-1浓度范围之间线性良好,r=0.9998;平均回收率为98.41%,RSD=1.64%。结论:本法准确、灵敏、重现性好、操作简便,主峰与杂质峰分离完全,可用于复方丹参渗透泵型控释片的质量控制。     

大剂量难溶性药物苯扎贝特渗透泵片的研制

 目的制备大剂量难溶性药物苯扎贝特单层渗透泵片,考察其释药的影响因素。方法以聚氧乙烯为载体和碳酸钠增溶相结合制备渗透泵片,并对影响释药的因素进行单因素考察。结果制备了大剂量难溶性药物苯扎贝特单层渗透泵片,聚氧乙烯主要影响释药的前期过程,而碳酸钠有助于最终释放完全。结论本渗透泵片使用了尽可能少的辅料,制备简便,能够达到12 h的恒速释放。     

香青兰总黄酮渗透泵片的制备及体外释药影响因素考察

目的:制备香青兰总黄酮渗透泵片,并对其体外药物释放影响因素进行研究。方法:紫外分光光度法测定渗透泵片体外释放度,考察不同处方和工艺对药物释放的影响。结果:促渗剂的种类及用量,碳酸氢钠用量,包衣增重对药物的体外释放均有显著影响。结论:渗透泵片制备工艺合理稳定,释药规律符合控释制剂要求。     

岩白菜素高载药量渗透泵型控释片的制备

目的:制备难溶性药物岩白菜素高载药量单室单层渗透泵型控释片。方法:以渗透泵片常用辅料为混合载体材料制备固体分散体,利用等渗原理优化片芯处方;以岩白菜素累积释放度为指标,采用星点设计-效应面法优化包衣处方。结果:PEG 1500质量分数1.30%,包衣增重9.5%时,制得的岩白菜素高载药量渗透泵片累积释放度接近80%,符合零级释药特征。结论:充分发挥辅料多种功能可有效提高渗透泵片载药量;优化片芯与衣膜处方的方法能显著缩短试验周期,为渗透泵制剂处方设计提供一种新思路。