Better detoxifying effect of ripe forsythiae fructus over green forsythiae fructus and the potential mechanisms involving bile acids metabolism and gut microbiota.

Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called "Qingqiao" and "Laoqiao" referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.

[Construction of serum-resistant cationic polymer α-CD-PAMAM and evaluation of its performances as gene delivery vector].

Polyamidoamine (PAMAM) dendrimers as synthetic gene vectors are efficient gene delivery systems. In this study, a kind of α-cyclodextrin-PAMAM conjugates polymer (Cy D-G1) was synthesized as a gene delivery vector. Based on ~1H NMR detectation, about 6.4 PAMAM-G1 molecules was grafted onto an α-CD core. Agarose gel electrophoresis revealed that Cy D-G1 could efficiently bind with DNA to condense them into nano-scale particles, which showed a similar binding capacity of PEI-25 K. Besides, it could protect DNA from DNase I degradation in a low N/P ratio. When N/P ratio in the CyD-G1/DNA polyplex was 40, the average particle size of CyD-G1/DNA polyplex was about 120 nm, and zeta potential was +21 mV. This polyplex could maintain its particle size in serum-containing solution within 360 min. In comparison with PEI-25 K carrier, CyD-G1 showed low cytotoxicity in various cell lines. Cell transfection results showed that CyD-G1 efficiently delivered DNA into cells at N/P = 80 compared with Lipofectamine 2000 and PEI-25 K. Unlike Lipofectamine 2000 and PEI-25 K, in serum-containing test condition, CyD-G1/DNA polyplex could maintain the transgene activities. The results of confocal laser scanning microscopy indicated that most DNA entered into cell nuclei within 4 h, and this phenomenon was consistent with the results calculated by flow cytometry. Taken together, CyD-G1 showed good transgene activities and the gene delivery vector could be used not only in vitro but also in vivo.

[Effect of water-soluble polymers on the inhibition of osthole crystallization].

This paper is to study the inhibitory effect of water soluble polymers--methyl cellulose (MC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC-M), poloxamer (F68) and polyvidon (PVP) on osthole (OST) crystallization and investigate the impact of polymer concentration and viscosity on crystallization behavior. Also, UV spectrophotometry method was used to determine the drug concentration at different time point to draw the OST concentration-time curve. Results show that HPMC has the most significant inhibition effect on OST crystallization, and drug concentration level is 1.61 times higher than that in control solution within 8 h followed by PVP (1.54) and MC (1.45) respectively. The kinetics of OST recrystallization can be described using first-order reaction, and the crystallization rate constants obtained by analyzing the regression equation indicate that HPMC-60SH-4000 and HPMC-60SH-10000 can greatly influence OST crystal formation. The dissolution rate of drugs precipitated from water-soluble polymer solutions is faster compared with controls in pH 1.2 HCl and pH 6.8 phosphate buffers, which demonstrated that water-soluble polymers can not only change the behavior of drug crystallization but markedly improve the dissolution rate of water insoluble drugs.

[Preparation and evaluation of clarithromycin emulsion for injection].

AIM: To prepare clarithromycin emulsion and investigate its pharmacokinetics in rats. And to do irritation test of the emulsion. METHODS: High pressure homogenization method was used to prepare clarithromycin emulsion, and the Nicomp380 machine was used to test the mean particle size and zeta-potential of clarithromycin emulsion. Irritation of emulsion was also evaluated compared with the positive control of clarithromycin solution using rat paw lick test and rabbit ear vein irritation test. Microbiological assay method was used for determining the drug concentration in plasma. Pharmacokinetics of two dosage forms in rats was also studied. RESULTS: The mean particle size and zeta potential of clarithromycin emulsion were 156 nm and -31.8 mV, respectively. The emulsion was stable during the storage time at 4 degrees C for 6 month. The pain caused by emulsion reduced significantly compared with that of clarithromycin solution based on the results of rat paw lick test and rabbit ear vein test. The drug concentration-time curves of clarithromycin emulsion and clarithromycin solution were similar and could be described by two compartment model. AUC(0-1) of clarithromycin emulsion and clarithromycin solution were (66.76 +/- 16.34) and (59.00 +/- 11.20) microg x h x mL(-1), respectively. CONCLUSION: Stable emulsion could be prepared using high pressure homogenization method, and irritation caused by i.v. injection could be reduced significantly by using clarithromycin emulsion.