Aim: To search for novel α_1-adrenoceptor(α_1-AR) antagonists. Methods: On the basis of hybridization principle with silodosin as the lead compound, twelve 5-[2-[4-[ ( substituted phenoxy) alkyl] piperazin-1-yl] propyl] indoline compounds were designed and synthesized by maintaining indoline while incorporating the 1-[(substituted phenoxy) alkyl] piperazine group. Results: The structures of synthesized target compounds were confirmed by the elemental analysis, IR, ESI-MS and ~1H NMR. Preliminary pharmacological test showed that pA_2 values of six target compounds were greater than 7. 50, which suggested that the compounds possessed considerable α_1-AR antagonic activity. Conclusion: 5-[2-[4-[ ( substituted phenoxy) alkyl] piperazin-1-yl] propyl] indoline compounds is potentially a new candidate for α_1-AR antagonist.

Aim: To establish an HPLC method for the determination of secnidazole and its related substances, and to elucidate the structure of the main related substances. Methods: HPLC was performed on an Agilent C_(18) (150 mm × 4. 6 mm, 5 μm) column. The mobile phase consisted of acetonitrile and 0. 1% formic acid solution( 10 : 90). The detection wavelength was set at 320 nm and the column oven was maintained at 30 ℃. The mass spec-trometry detector was equipped with an ESI source with a temperature of 350 ℃, and set at positive ion monito-ring model The spray chamber pressure was 0. 34 MPa. The drying gas flow rate was 10 L/min. Results: Sec-nidazole was completely separated from the impurities. The calibration curve of secnidazole was linear over the range of 0. 10-1 500. 0 μg/mL with the correlation coefficient of 0. 999 9. The contents of secnidazole in the sam-ples were 100.5%, 100.3% and 100.7%, respectively, and those of the related substances were 0.463%, 0. 488% and 0.465%, respectively. The three related substances were identified by HPLC-UV-MS~n as 2-methyl-5-nitroimida-zole and the isomerides of secnidazole, respectively. Conclusion: The developed method is reliable for the quality control and determination of related substances of secnidazole.

Aim: To study the effect of Eudragit S-100, a pH-responsive polymer, on protein refolding level, using recombinant human keratinocyte growth factor-2 (rhKGF-2) as a model protein. Methods: The refolding of rh-KGF-2 was performed by directly diluting denatured rhKGF-2 into a refolding buffer containing different concentrations of Eudragit. The ability of Eudragit S-100 to enhance protein refolding level was investigated using MTT assay, reverse phase HPLC, fluorescence emission spectroscopy and circular dichroism spectroscopy. Results: The addition of Eudragit S-100 in the refolding buffer significantly increased the rhKGF-2 refolding yield to 71%, when dilution refolding was conducted at 0. 5 mg/mL rhKGF-2. The outcome from the refolding study showed possibility of a special interaction between rhKGF-2 and Eudragit, suggesting that the refolding-enhancing ability of Eudragit S-100 was due to this interaction between Eudragit S-100 and rhKGF-2. Mean while, the result showed that the concentration of urea was also an important factor for the optimization of the refolding in the presence of Eudragit. Conclusion: Eudragit S-100 can significantly increase the refolding level of rhKGF-2.

HepG2 cells were pre-incubated with insulin (Ins 0,1,0. 1,0.01 μol/L) and dexamethasone ( Dex 0,3,0. 3,0.03 μol/L) alone or together for 24 h to induce insulin resistance (IR) in vitro, the resistant level was estimated by glucose consumption, the optimal model of insulin resitance was chosen, and at the same time its lasting time of resistance was determined. In order to investigate the effects and mechanisms of mifepristone on in sulin-resistant HepG2 cells induced by insulin and dexamethasone, mifepristone and pioglitazone were adminis tered 24 h after the optimal model of insulin-resistant HepG2 cells was established. The glucose consumption, in tracellular concentrations of glucose, glycogen, ATP, and free fatty acid (FFA) in each group were detected. The expression of InsR-mRNA and GR-mRNA was detected by semi-quantitative reverse transcription and polymerase chain reaction (SqRT-PCR). Results revealed that pretreatment with insulin (0. 1 μmol/L) and dexamethasone (0.3 (μol/L) for 24 h caused optimal insulin resistance of HepG2 cells which lasted for 36 h. Compared with control group, the glucose consumption, intracellular glucose, glycogen, ATP contents and the level of InsR-mRNA in model cells decreased while FFAs concentrations and GR-mRNA increased. However, the tendency of insulin resistant HepG2 cells was obviously attenuated by pioglitazone at the concentration of 0. 2 mmol/L and mifepris tone at 200μmol/L and 20 μol/L while mifepristone at 2 μol/L had no effect on insulin-resistant cells. The findings indicated that mifepristone at 200 μol/L and 20 μol/L improved the insulin resistance via modulating intracellular glucolipid metabolism and the expression of InsR-mRNA and GR-mRNA.

Herba Epimedii (named Yinyanghuo in Chinese) of the family Berberidaceae is one of the most famous traditional Chinese medicines (TCMs) recorded in the pharmacopoeia of the People's Republic of China.Total flavonoids of Epimedium (TFE) are considered to be its active components.TFE content was measured by ultraviolet method and its representative constituents,icariin and epimedin C,were determined by high performance liquid chromatography.The test results from 36 samples of 4 species showed that the contents differed significantly in different species.The average data of the summation (icariin and epimedin C) content were 20.83,7.61,14.43,23.29 mg/g in Epimedium pubescens Maxim.,E.koreanum Nakai.,E.brevicornum Maxim.,E.sagittatum (Sieb.Et Zucc.) Maxim.,respectively.Both E.sagittatum and E.pubescens performed better than the other two batches.E.sagittatum hardly has any circulation in Chinese herbal medicine market.The results showed that E.pubescens,which had much more amounts of icariin,epimedin C and TFE than those of other species,has a better quality and may be considered as potential anti-osteoporosis drug.

Aim: To investigate the mechanism of anti-proliferation, anti-migration and anti-angiogenic effects of tanshinone ⅡA. Methods: In this study, MTT, 2-D/3-D migration, tube formation, PCR, chick embryo chorioallan-toic membrane (CAM) were used to evaluate the anti-proliferation, anti-migration and anti-angiogenic effects of tanshinone ⅡA. Results: Tanshinone ⅡA significantly inhibited the proliferation of human breast cancer line MDA-MB-435 with an IC_(50) of 21 nmol/mL And it is showed that breast cancer cells migration was effectively prevented by tanshinone ⅡA at 5 and 6 nmol/mL in a wound healing assay and a transwell migration assay. In ad-dition, tanshinone ⅡA inhibited the tube formation of newborn cattle aortic endothelial cells( NCAECs) after 2 h co-incubation with MDA-MB-435. These effects were not due to the inhibition of NCAECs proliferation; because tanshinone ⅡA non-selectively inhibited NCAECs growth with an IC_(50) of 124 nmol/mL Tanshinone ⅡA showed dose-dependent inhibitory effects on mRNA expression of VEGF and two transcription factors (HIF-1α/c-Myc) . Tashinone ⅡA was also found to inhibit angiogenic in vivo in the CAM assay. Conclusion: These results suggest that tanshinone ⅡA may exert its anti-proliferation, anti-migration and anti-angiogenic effects through down-regu-lating two transcription factors and VEGF. These novel anti-proliferations, anti-migrations, anti-angiogenic activi-ties of tanshinone ⅡA are likely to contribute to its cancer chemopreventive and therapeutic potential, especially in the treatment of breast cancer.

Aim: To study the pharmacokinetic effects of salvianolic acid B( Sal B) on danshensu( DSS) in Danshen injection in rats. MGthod: Following the intravenous administration of Danshen injection and Danshen injection added with Sal B to rats, the plasma kinetic study, tissue distribution and urine excretion were studied. The plasma kinetic study was also investigated by giving DSS and DSS in combination with Sal B to rats. Plasma, tissue and urine drug levels of danshensu were analyzed by LC-MS. Results: Compared with danshensu given alone, no significant difference of the pharmacokinetic behavior of danshensu was found when danshensu was given in combination with salvianolic acid B. However, compared with Danshen injection given alone, the pharmacokinetic behavior of danshensu changed remarkably when Danshen injection was given in combination with salvianolic acid B which might be caused by the decrease of DSS in kidney distribution and urine excretion. Conclusion: The pharmacokinetic effects of salvianolic acid B on danshensu depend on the existence of multiple components in Danshen injection. Results suggest that the pharmacokinetic interactions of the multiple components are closely related to the integrity of herbal medicines.

Aim: To develop a new preparation consisting of colon adhesive pellets of sodium 4-amino salicylate for the treatment of ulcerative colitis, and to characterize the adhesive of the prepared pellets. Methods: Centrifu-gation-granulation was used to prepare sodium 4-amino salicylate pellets into which HPMC K4M and Carbomer 934P as matrix were incorporated. The pellets were coated with Surlease~((R)), and filled into enteric-coated cap-sules. The release of sodium 4-amino salicylate from the pellets was evaluated in the pH 7. 4 buffer. The adhesive property of the pellets was characterized by evaluating the transit rate of the pellets in the rat intestine in vivo, and by determing the remaining( %) of the pellets in the isolated rat colonic segment in vitro. The adhesive of the pel-lets in vivo was also verified by X-rays. Results: It was shown that the resultant pellets of round shape, good uni-formity in size, and favorable rigidity possessed the colon-adhesive and sustained-release properties. Conclusion:The simple, economical and practical approach was sucessfully utilized in the preparation of sodium 4-amino sa-licylate pellets with the remarked colonic adhesion and targeting.

Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathe-matical and statistical methods to characterize,understand,and predict a drug's pharmacokinetic,phannacodyna-mic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.

Aim: To establish the HPLC and LC-MC methods for the quality analysis of the different species of Radix Paeoniae Alba cultivated in Bozhou. Methods: The LC-MS method was applied to analyze the chemical composition of the cultivated species, the HPLC method was applied to determine the contents of paeoniforin, ben-zoic acid and paeonivayin in crude drugs and processing products. Results: 10 characteristic peaks were identified by LC-MS with reference standards. The significant difference was observed in the chemical compositions of 3 cultivated species. The significant difference was observed in the chemical compositions of 3 cultivated species. The content of paeoniflorin was increased significantly after traditional processing. The results indicated the 4-year-old pubang and 5-year-old xiantiao are the best cultivated species. Conclusion: The methods are simple, rapid and precise to assess and control the quality of different species of Radix Paeoniae Alba cultivated in Bozhou.