OBJECTIVE:To prepare aspirin chitosan-sodium alginate microcapsules(ACSPM)and to investigate its optimal formula and releasing mechanism.METHODS:The formula of ACSPM was optimized by the orthogonal design with entrapment ratio as index,and then ACSPM was prepared,with its release rate determined as well.The releasing mechanism of aspirin from the microcapsules was established by equation fitting of releasing kinetic model.RESULTS:The prepared microcapsules were uniform in size and contents.The optimized formula was as follows:the concentration of sodium polymannuronate and chitosan were 3.0% and 1.0%,respectively,and the proportion of polymannuronate to aspirin was 1∶ 4.The in vitro drug release was in line with both Higuchi equation and Peppas equation.CONCLUSION:This preparation technology was simple and the drug releasing mechanism of the preparation was chiefly characterized by drug diffusion including bulk erosion non-Fickian process.

OBJECTIVE:To investigate the preparation technique and optimal formulation of ketoconazole calcium alginate gel beads.METHODS:Ketoconazole calcium alginate gel beads were prepared by droplet method.The orthogonal experiment was carried out with encapsulation efficiency(EE)and drug loading(LD)as indexes to optimize the optimal formulation of the calcium alginate gel beads.The encapsulation efficiency and drug loading amount for the optimized formulation were determined,and the optimized formulation was compared with crude drug in respect of the in vitro drug release behavior.RESULTS:The result showed that the optimal formulation was as follows:2.0% Na-alginate and 0.3mol? L-1 CaCl2 with the ratio of Na-alginate:ketoconazole at 2∶ 1.The average EE and LD were(90.53? 2.32)% and(31.51? 2.08)%,respectively,and the slow-release was better as compared with that of the crude drug.CONCLUSION:The preparation procedure is simple,feasible,stable and reproducible.

To review and analyze the pharmacological effect and underlying mechanism of Chinese lobelia. Methods:The references from home and abroad on the pharmacological effect and mechanism of Chinese lobelia in recent years were summarized and analyzed. Results:Chinese lobelia had wide range of pharmacological effects, such as anti-tumor, endothelial cells regulation, an-algesic and anti-inflammatory effect, inhibition against alpha glycosidase enzymes and myocardial ischemia reperfusion et al. Conclu-sion:A large number of effective compositions are in Chinese lobelia and the biological activity is extensive. The mechanism of biologi-cal activity should be further studied in-depth.

OBJECTIVE To investigate the effect of the dosing time on the pharmacokinetics oferlotinib.METHODS Female C57BL mice were contained under standardized 12h light/dark circadianconditions (lights on at 7:00,off at 19:00)for 3 weeks and randomly assigned into six groups.Erlotinibhydrochloride was orally administrated to the mice in each group at 8:00,12:00,16:00,20:00,24:00and 4:00,respectively.Blood was drawn from the eyeballs of the mice at 12 different time points aftereach administration.The plasma concentration of erlotinib was determined through a high-performanceliquid-chromatographic assay and the parameters were calculated by WinNonlin. RESULTSThe area under curre (AUC)and mean residence time (MRT)of these groups were apparently differ-ent.AUC0 ~24 h and MRT0 ~24 h were the lowest in the 20:00 administration group as compared to othergroups (P<0.01 ).Tmax of the 20:00,24:00 and 4:00 groups was apparently higher than that of the8:00 and 12:00 groups (P<0.01 ).The clearance of the light phase groups was lower than that of thedark phase groups (P<0.01 ),with the highest in the 20:00 group.The peak value of cmax appeared inthe 12:00 group and the lowest in the 20:00 group (P<0.01 ).CONCLUSION Circadian rhythm playsa critical role in pharmacokinetics of erlotinib in mice.

AIM: To investigate the effect of CD_8+ cells from aplastic anemia (AA) patients and its histamine type II (H_2) receptors on the growth of normal CFU-Mk. METHODS: The effects of CD_8+ cells and/or cimetidine, on normal human CFU-Mk growth were studied by using CFU-Mk assay. RESULTS: The CD_8+ cells from the perpheral blood of AA patients significantly suppressed the growth of normal allogeneic CFU-Mk. This inhibitory effect was blocked by cimetidine at concentration of 1.0?10~-5 mol/L. 1.0?10~-5 mol/L cimitidine alone didn't inhibit the growth of normal CFU-Mk. CONCLUSION: H_2 receptor antagonist cimitidine abolishes the suppressive effect of AA patients CD_8+ cells on the growth of normal CFU-Mk.

Objective:To compare the steam distillation( SD) and supercritical CO2 ( SFE-CO2 ) method in the extraction of vola-tile constituents from such 3 traditional Chinese drugs as cnidium monnieri, radix sileris and atractylodes lancea in compound Kuhuang prescription. Methods:Essential oil was extracted from the 3 traditional Chinese drugs by SD and SFE-CO2 method, respectively. The components were identified by GC-MS, and their relative contents were calculated with peak area normalization method. Results:To-tally 36 components were isolated and identified using SD extraction and 31 components were identified using SFE-CO2 extraction, a-mong them, 22 components were the same and their relative molecular weight mainly concentrated within 200-230. Conclusion: SFE-CO2 method can extract effective components from the 3 traditional Chinese drugs in compound Kuhuang prescription with higher selec-tivity, which is the more suitable extraction method for essential oil from the prescription.

OBJECTIVE:To optimize the water-extraction technology of Compound kuhuang formulation. METHODS:The wa-ter-extraction technology of Compound kuhuang formulation was optimized by orthogonal design,with the total contents of matrine and oxymatrine,the total content of prim-O-glucosylcimifugin and 5-O-methylvisamminol,the content of berberine hydrochloride and extract yield,and with the extraction time,amount of water(3 reflux extractions)and soaking time as the factors;and verifi-cation tests were conducted. RESULTS:The extraction time had significant effect on comprehensive evaluation value (P<0.05). The optimal water-extraction technology was as follows as extraction time of 120 min,water amount of 8,6,and 6 times as the amount of herbs,and soaking time of 20 min. In verification tests,the average total content of matrine and oxymatrine was 3.152 6 mg/g(RSD=1.03%,n=3),that of prim-O-glucosylcimifugin and 5-O-methylvisamminol was 4.977 2 mg/g(RSD=2.27%,n=3),the average content of berberine hydrochloride was 3.345 0 mg/g (RSD=1.19%,n=3) and the average extract yield was 49.23%(RSD=2.43%,n=3). CONCLUSIONS:The optimal water-extraction technology of Compound kuhuang formulation is stable and feasible.

Objective To establish the standard for quality control ofQingyan Granule. Methods The chief components of the preparation, Sophora Tonkinensis radix et rhizoma, Adenophorae radix, Lonicera japonica caulis, and Ophiopogonis radix were identified by TLC qualitatively. The contents of licorice glycosides and glycyrrhizic acid were determined by HPLC. The separation was performed on Thermo Syncronis C18 column (4.6 mm×250 mm, 5μm) with mobile phase consisted of acetonitrile with 0.05% phosphoric acid solution (A)-0.05% phosphoric acid solution (B), and gradient elution (0-8 min, 19%A;8-35 min, 19%→50%A). Detection wavelength was 237 nm, and flow rate was 1 mL/min.Results The spots in TLC were clear. There were spots with same color on the corresponding location of reference substance and reference herbal, negative control without interference. The linear range for licorice glycosides was 0.05-0.5μg (r=0.999 9). The average recovery was 99.97%, RSD=1.74% (n=9). The linear range for glycyrrhizic acid was 0.1-2μg (r=0.999 9). The average recovery was 99.74%, RSD=1.28% (n=9). Conclusion The method is simple, accurate, with high reproducibility, which can be used for quality control ofQingyan Granule.

AIM:To explore the changes of the subsets and HLA-DR expression of dendritic cells and their concerning cytokine levels in peripheral blood of patients with breast cancer.METHODS:The subsets of the precussors of dendritic cells(pDC)in the peripheral blood of 57 cases of patients with breast cancer before operation and a week or six months after operation and 20 cases of healthy controls were analyzed by four-color FCM.The levels of IL-12p40,IL-10,IFN-? and IL-4 in the plasmas were tested by ELISA.RESULTS:Among 57 cases of patients with breast cancer,2 cases in Ⅲ phase and 4 cases in Ⅳphase expressed deficiency of pDC,the ratios of pDC1/pDC2 in the other cases inⅠ,Ⅱ,Ⅲ,Ⅳ phase were respectively 1.62?0.59,1.41?0.63,0.91?0.32,0.81?0.29 before operation,which were markedly lower than those in controls(1.94?0.44).The ratios of pDC1/pDC2 in the cases inⅠ,Ⅱ,Ⅲ phase were 1.71?0.47,1.52?0.54,1.04?0.36 a week after operation,which were the same as those in pre-operation,but markedly lower than those in controls.The ratios of pDC1/pDC2 in the cases inⅠ,Ⅱ,Ⅲ phase were 1.92?0.72,1.63?0.65,1.28?0.34 six months after operation,which were markedly higher than those in pre-operation,meanwhile,to compare with controls,those were still lower for patients in Ⅱ,Ⅲ phase except in Ⅰphase.No difference between patients and controls in the expression of HLA-DR of pDCs and the levels of IL-12p40,IL-10,IFN-?,IL-4 in plasmas and the ratios of IL-12p40/IL-10,IFN-?/IL-4 was observed.CONCLUSION:The ratios of pDC1/pDC2 in peripheral blood of patients with breast cancer inⅠ-Ⅳ phase are decreased.Parts of patients in Ⅲ,Ⅳ phase are deficiency of pDCs.HLA-DR expression of DCs and the ability of DCs which secret the concerning cytokines do not change as pDC subsets change.pDC subsets improve markedly inⅡ,Ⅲ phase patients and recover to the normal level inⅠphase patients after operation.

AIM: To establish a arsenic trioxide (As 2O 3 )-resistant leukemic cell line to explore the mechanism of resistance to As 2O 3, and the relationship between the resistant cell line and the multidrug resistance was also investigated. METHODS: The arsenic trioxide (As 2O 3 )-resistant leukemic cell line was established by exposing the cells to the increasing concentration of As 2O 3. MTT assay was used to detect the cytotoxicity. Cell cycle was detected by PI assay. Flow Cytometry was used to detect the P-glycoprotein on the surface of the cells, the intracellular concentration of DNR, and the immuetype of the cells. RESULTS: The cell doublings time and the cell cycle of the arsenic trioxide (As 2O 3 )-resistant leukemic cell line, K562/AS2, is similar to that of K562. The relative resistant fold of K562/AS2 to As 2O 3, DNR, VP16 and Ara-C was 7.4, 2.9, 3.8 and 1.1, respectively. The relative resistant fold of multidrug resistant cell line, K562/ A02, to As 2O 3, DNR, VP16 and Ara-C was 0.8?94?2.5 and 0.9, respectively. The fluorescence of the P-glycoprotein on the surface or of the DNR inside the cells detected was not significantly different between the K562 and the K562/AS2 cell lines. CONCLUSIONS: A cell line, K562/AS2, resistant to clinical achieving level (2 ?mol/L) of As 2O 3 has been established. The relative resistant fold of K562/ AS2 to As 2O 3 is about 7.4 fold to the parent K562 line sensitive to As 2O 3. Partial resistance of K562/AS2 to DNR and VP16 is observed , the mechanism of which is unrelated to the P-gp, the expression product of multidrug resistance gene 1 (mdr1).