OBJECTIVE:To provide experimental evidence for the secondary development of breviscapine.METHODS:The solubility of breviscapine in various solvent and aqueous media at various pH were determined by HPLC.The ionization constant(pKa)were determined by solubility method.The oil/water partition coefficient was determined by shaking bottle method.The stability of breviscapine solution at 25 and 37 ℃ and the effects of EDTA-2Na and NaHSO 3 on it were investigated.RESULTS:Scutellarin belonged to weak acid constitutent,and its pKa was 3.29;its solubility was markedly affected by the pH of the environment;oil/water partition coefficient of it was 0.27;the solubility of scutellarin was in low level in various organic solvents.At 25 ℃,scutellarin was stable relatively in solution with pH 2-5 at 25 ℃;at 37 ℃,scutellarin was stable relatively in solution with pH 3-5,and the degradation mechanism of scutellarin can be explained by specific acid/base catalysis.The addition of EDTA-2Na or/and NaHSO 3 could improve the stability of scutellarin in water significantly.CONCLUSION:This study provides instructive information for secondary development of breviscapine and confirms the method for improving the stability of breviscapine in aqueous solution.

OBJECTIVE: To prepare Corydalis decumbens total alkali multivescular liposomes and evaluate it in vitro. METHODS: C. decumbens total alkali multivescular liposomes were prepared by multiple emulsion method with encapsulation efficiency as index and with ratio of phospgatidycholine (PC) to drugs, ratio of PC to triolein (TO), ratio of OC to phosphatidylserine (PS) and ratio of PC to cholesterin (CH) as factors. The morphology, particle size, release in vitro of preparation were evaluated. RESULTS: The ratio of PC to drug, ratio of PC to TO, ratio of PC to PS and ratio of PC to CH were 10 ∶ 2,3 ∶ 1,4 ∶ 3,1 ∶ 2.5. The encapsulation efficiency of optimized formulation was (50±3)%. The multivescular liposomes assumed as spherical with average particle diameter of 22.0 μm. The drug release duration in normal saline was 2 days. CONCLUSION: The preparation technology is stable and feasible.

Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility.

Lappaconitine instead of its hydrobromide salts has been encapsulated in poly (lactide-co-glycolide) acid (PLGA) microspheres by the simple o/w emulsion solvent evaporation technique. The effects of several variables including emulsifier (polyvinyl alcohol, PVA) concentration, stirring speed, PLGA concentration and drug/polymer mass ratios on quality of microspheres have been investigated. The particle size and size distribution can be controlled by PVA concentration, stirring speed and PLGA concentration. The entrapment efficiency and the burst release of lappaconitine from drug-loaded microspheres were dominantly affected by the drug/polymer mass ratio and PVA concentration. The best parameters of formulation were 1.5% PVA, the PLGA concentration of 50 g/L, and the stirring speed of 800 rpm and drug/polymer of 1:5. The optimized formulation has a mean particle size of 19.3 +/- 0.93 microm, mean entrapment efficiency of 70.77 +/- 3.23% and mean drug loading of 11.45 +/- 0.47%. Based on the optimized parameters of formulation, the effects of oil/aqueous solubility partition ratio of drug on entrapment efficiency of drug-loaded microspheres prepared by o/w emulsion solvent evaporation were further studied. A good linear relation existed between the partition ratio and entrapment efficiency. The optimized microspheres were characterized by SEM, FT-IR, DSC and XRD. SEM shows spherical and smooth surface and uniform size distribution. The results of DSC, FT-IR study reveal no interaction between drug and polymer. The results of the XRD study indicate lappaconitine trapped in microsphere exists in form of an amorphous or disordered crystalline status in polymer matrix. The in vitro release models were evaluated with two different groups of drug-loaded microspheres including microspheres washed with distilled water and 0.01N HCL, respectively. The drug release profile of lappaconitine-loaded microspheres washed with distilled water agreed with zero order equation and that of the latter better agreed with first order equation.

In this study, an infectious HCV monocistronic reporter virus was constructed by inserting an EGFP gene into the C-terminus of NS5A in the JFH-1 genome. A robust adaptive mutant, which could produce infectious virions as robustly as the JFH-1 wild type in Huh7.5.1 cells, was subsequently isolated by monitoring EGFP fluorescence. Full genomic sequencing revealed five amino acid substitutions, three located in the helicase domain of NS3 and two positioned in the C-terminus of NS5A. Reverse genetics studies suggested that the NS3 and NS5A mutations acted synergistically to enhance virus production capability possibly by accelerating the virion assembly efficiency but did not affect the replication competence of the adaptive reporter virus. Further analysis revealed that the M260K and T462I substitutions in NS3 and NS5A, respectively, were the key mutations. These adaptive mutations were also effective in the context of the JFH-1 genome.