Bioequivalence Study of Clobazam Tablet in Chinese Healthy Subjects / 医药导报

Objective To study the pharmacokinetic characteristics of clobazam tablet in Chinese healthy subjects and evaluate the bioequivalence of test preparation(T)and reference preparation(R)under fasting or fed conditions.Methods A randomized,open-label,single-dose,two-period,two-way crossover bioequivalence trial was performed.34 healthy subjects were enrolled in fasting study and 30 in fed study.Each subjects received a single dose of T 20 mg or R 20 mg with a washout period of 28 days.Plasma concentrations of clobazam and its active metabolite,N-desmethylclobazam were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The pharmacokinetic parameters of clobazam and N-desmethylclobazam were calculated by non-compartment model.Geometric mean values for the T/R ratios of clobazam's main pharmacokinetic parameters and their corresponding 90 percent confidence intervals(CI)were evaluated to assess bioequivalence of the two preparations.Results In fasting study,the 90 percent CI of the geometric mean values for the T/R ratios were 94.46 to 103.82 percent for Cmax,99.64 to 103.62 percent for AUC0-tand 99.39 to 103.51 percent for AUC0-∞,respectively.In fed study,the 90 percent CI of the geometric mean values for the T/R ratios of were 93.86 to 106.02 percent for Cmax,100.37 to 104.51 percent for AUC0-tand 100.71 to 104.63 percent for AUC0-∞,respectively.Conclusion In this study,the 90 percent CI of the geometric mean values of Cmax,AUC0-tand AUC0-∞ for T/R ratios were all within the acceptable bioequivalence limits of 80 to 125 percent for clobazam.Therefore two formulations were considered bioequivalent.

Isocryptotanshinone Induced Apoptosis and Activated MAPK Signaling in Human Breast Cancer MCF-7 Cells / 한국유방암학회지

PURPOSE: Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. METHODS: The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. RESULTS: ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. CONCLUSION: Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.

Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways

Neocryptotanshinone (NCTS) is a natural product isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. In this study, we investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) cells. MTT results showed that NCTS partly reversed LPS-induced cytotoxicity. Real-time PCR results showed that NCTS suppressed LPS-induced mRNA expression of inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Moreover, NCTS could decrease LPS-induced nitric oxide (NO) production. Western blotting results showed that NCTS could down-regulate LPS-induced expression of inducible nitric oxide synthase (iNOS), p-IκBα, p-IKKβ and p-NF-κB p65 without affecting cyclooxygenase-2 (COX-2). In addition, NCTS inhibited LPS-induced p-NF-κB p65 nuclear translocation. In conclusion, these data demonstrated that NCTS showed anti-inflammatory effect by suppression of NF-κB and iNOS signaling pathways.

Formulation Optimization and Dissolution of Compound Pearl Powder Effervescent Granule / 中国药房

OBJECTIVE:To optimize the formulation of Compound pearl powder effervescent granule and study its release behavior in vitro. METHODS:The contents of anhydrous citric acid,sodium bicarbonate,and lactose in the formulation were optimized by uniform design method with the consumption of ethylenediamine tetraacetic acid(EDTA) as index meanwhile giving consideration to the foaming height and pH of the solution. The dissolution of calcium carbonate in Compound pearl powder effervescent granule,self-made calcium carbonate tablets and self-made pearl power in distilled water and hydrochloric acid were investigated. RESULTS:The optimized formulation of the Compound pearl powder effervescent granule was stated as follows:10.0 g anhydrous citric acid,2.5 g sodium bicarbonate,and 5.0 g lactose. There were significant differences across the 3 different preparations in dissolution rates. CONCLUSION:The prepared Compound pearl powder effervescent granule is characterized by fast and complete drug release. Its solution is acid and indicated for specific population.

Intenstinal absorption mechanism and in vitro-in vivo correlation of norcantharidin nanoparticles / 中草药

0.05).The absorption of NCTD was a first-order process with passive diffusion mechanism.The absorption law in vivo was the same as in vitro,the correlation coefficient between them was 0.999 4.Conclusion NCTD-CS-NP could improve the absorption of NCTD in rat small intestine.NCTD is well absorbed at the superior and middle segments of intestine.The concentration of NCTD has no distinctive effect on the absorption kinetics.The release of drug in vitro and its uptake is well correlated.

Identification of irisquinone hydroxypropyl-?-cyclodextrin inclusion compoundand its thermodynamic stability / 中草药

Objective To parperare and identify the irisquinone-hydroxypropyl-?-cyclodextrin (irisquinone-HP-?-CD) inclusion compound. The inclusion mechanism and mol ratio of irisquinone and HP-?-CD were studied simultaneously. Methods The irisquinone-HP-?-CD was prepared with lyophilization technique. The mol ratio between host and guest moleculars was also researched by molecular gradient and continuing variational methods in inclusion processing. At the same time, the inclusion compound was identified by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) methods, respectively. Results The above-mentioned systems showed the mol ratio of HP-?-CD-irisquinone (2 : 1) and the inclusion compound enhanced remarkably the most solubilization and more combined constant of irisquinone in 25, 35, and 45℃. The lyophilized powder had been formed inclusion compound by identifying. Conclusion It is advantageous to increase the solubilization and to strengthen the stability of irisquinone by preparing inclusion compound.

Solubilization of hydropropyl-?-cyclodextrin to paclitaxel and its relative molecular inclusion mechanism / 中草药

Objective To investigate the solubilitization effect of macromolecular paclitaxel with cyclodextrin and mechanism between inclusion complex and drugs. Methods The influence effects on paclitaxel solubility were studied with ?-cyclodextrin (?-CD) and hydroxypropyl-?-cyclodextrin (HP-?-CD) as inclusion carriers. The chemical shifts of hydrogen atom in host and guest molecules were also investigated with 1H-NMR. Results The form of inclusion complex was responsible by host molecules and the enhancement solubility of paclitaxel in HP-?-CD was larger than that in ?-CD and increased with the ratio increasing. The benzene ring in the molecular of HP-?-CD and paclitaxel showed the most significant effect. Conclusion The solubility of diossolved paclitaxel is improved by hydroxypropyl-?-cyclodextrin.

Characterization and in vitro release of chitosan nanoparticles loading norcantharidin / 中草药

Objective To prepare the chitosan nanoparticles(particle-diameter

Preparation of norcantharidin N-galactosylated chitosan nanoparticles and its characteristics / 中草药

Objective To synthesize N-galactosylated chitosan as hepatocyte-targeting carrier and prepare loading norcantharidin nanoparticles.Methods N-Galactosylated chitosan was prepared by carbodiimide condensation reaction;loading norcantharidin nanoparticles were achieved by ionic cross-linkage process with N-galactosylated chitosan as carrier.Taking distribution of particle size,entrapment efficiency,and drug-loading capacity as comprehensive indexes,the orthogonal test design was used to optimize the preparation process and the in vitro release was investigated.Results Substitution degree of N-galactosylated chitosan reached to 8.92%.Novel nanoparticles were spherical,average in particle size(118.7?8.84)nm,entrament efficiency(57.92?0.40)%,drug-loading capacity(10.38?0.06)%,and the in vitro release followed Higuchi equation.Conclusion Effect of drug sustained release of galactosylated chitosan nanoparticles is significant.

Preparation technique of irisquinone-hydroxypropyl-?-cyciodextrin inclusion complex with orthogonal design / 中成药

AIM: To screen and optimize the preparation conditions of irisquinone-hydroxypropyl-?-cyclodextrin inclusion complex (Irisquinone-HP-?-CD) with stiring method. METHODS: The load-drug and recovery of irisquinone were adopted as the index, host-guest molar ratio, alcohol concentration and stiring rate as factors, have been investigated in the techniques of irisquinone-HP-?-CD. RESULTS: The load-drug and recovery of irisquinone-HP-?-CD were respective ( 15.79 ?0.22)% and ( 92.03 ?6.26)% by optimizing conditions which were host-guest molar ratio 2∶1, 90% EtOH and stiring rate 800r?min -1. At the same time, the dissolution test showed that irisquinone was faster released from inclusion complex than that from capsules and mixture dosage form. CONCLUSION: The optimizing techniques fit to prepare irisquinoe-HP-?-CD in industry.

Preparation of Irisquinone freeze-drying Injection and its stability / 中成药

AIM: To prepare the irisquinone freeze-drying injection and investigate its stability. METHODS: The degradation pattern of irisquinone and its effects were measured. At the same time, the stability of freeze-(drying) injection by classic thermostatical test. RESULTS: Irisquinone solution was unstable to heat and its content decreased remarkably in acid and alkaline solutions. The result showed that oil/water partition coeffecient of irisquinone was very large. The irisquinone-hydropropyl1-?-cyclodextrin inclusion complex freeze-drying injection was very effective to enhance the drug stability. CONCLUSION: Irisquinone inclusion complex injection has character of good stability.

Absorption of irisquinone-Hydroxypropyl-?-Cyclodextrin Inclusion Complex in intestinal and its pharmacokinetics in rats / 中成药

AIM: To investigate the intestinal uptake of risquinone in two dosage forms-capsule and irisquinone-?-hydroxyprol-?-cyclodextrin(HP-?-CD) in rats and its pharmacokinetics. METHODS: Comparing with capsule,the accumulation uptake of irisquinone from HP-?-CD inclusion complex were tested in suit in vivo and the correspondence between pharmacokinetics behavior and uptake of irisquinone in rats were simultaneously analysised. RESULTS: The intestinal absorption rate of irisquinone were 0.047 h~(-1) to capsule and 0.180 h~(-1) to irisquinone-HP-?-CD,respectively.The intestinal uptake of irisquinone in rats was positive correlation with its release from capsule in vitro.The accumulated uptake of irisquinone were 29.58% from capsule and 69.63 % from irisquinone-HP-?-CD.The pharmacokinetics of irisquinone in two formulas were coincidence with one-compartment model in rats.The absorption half life(T_(1/2(ka))) was 0.23 h to irisquinone-HP-?-CD and 0.49 h to capsule.The relative bioavailability of irisquinone-HP-?-CD was 133.9%. CONCLUSION: Inclusion complex may enhance intestinal uptake of drug and improve its bioavailability.

Formulation optimization and the in vitro release characteristics of Fuyankang Dispersible Tablets / 中成药

AIM:To optimize the formulation of Fuyankang Dispersible Tablets and study the in vitro release characteristics of them. METHODS: The orthogonal design was used to obtain the optimal formulation with the disintegration,hardness and weight of tablets as markers,and then dispersible uniform and the in vitro release characteristics of the optimal formulation were studied with dispersed experiment and PR-HPLC,respectively.(RESULTS:)The proportion of each adjuvant in the optimal formulation consisted of 10% MCC,4% L-HPC,12% PVPP.The optimized dispersible tablets disintegrated in 1 min,the hardness was 5.24 kg,the average weight was 0.407 g;the dispersible uniform was excellent,and the settling velocity equation was logF=-0.028-1.001?10~(-3)t;The released rate parameters of Fuyankang Dispersible Tablets were T_(50)=3.0 min and T_d=4.0 min,which were remarkly less than that of the control group,T_(50)=14.28 min and T_d=16.62 min(P

Pharmacokinetics of Paclitaxel Lyophilized Injection in rat / 中成药

AIM: To study the pharmacokinetics of Paclitaxel Lyophilized Injection and Taxol in rats. METHODS: Paclitaxel inclusion lyophilized Injection was prepared with hydroxylpropyl ? inclusion as the inclusion vehicle. At the same time, Paclitaxel Lyophilized Injection pharmacokinetic pattern and parametes had been modeled with 3p87 program and statistic rules comparing with Taxol. RESULTS: Paclitaxel Lyophilized Inject and Taxol abided by two department model. The parametes T 1/2? (3.40?0.27)h and AUC (34.46?4.34) mg?L -1 ?h,MRT 3.50 h to Lyophilized Injection and T 1/2? (3.50?0.62)h, AUC (25.73?6.42) mg?L -1 ?h,MRT 2.52 h to Taxol. CONCLUSION: The results indicate that distribution rate of the two preparations are in coincidence with in rats and Paclitaxle Lyophilized extends the retention time of paclitaxel in rats.

Preparation Technique Optimization of Norcantharidin Liposome and Its Pharmaceutical Properties / 中国药房

OBJECTIVE:To optimize the preparation technique of norcantharidin liposome(NL) and study its pharmaceutical properties. METHODS: With envelopment efficiency(EE), mean particle size and span of the liposome as indexes, the effects of thin-film dispersion method, injection method, reverse phase evaporation and reverse phase film-evaporation method on the EE and particle size of the NL were evaluated. And the uniform design was used to optimize the reverse phase film-evaporation preparation technique of NL with the amount of phospholipid (X1), the mass ratio of phospholipid/ cholesterol (X2), the sonde-type ultrasounding times (X3), the dilution times of buffer phosphate (X4), the volume ratio of oil/water phase (X5) and the mass ratio of lipoids/ drug (X6) as integrated indexes. A verification test was performed on the optimal technique. RESULTS: The formulation prepared by reverse phase film-evaporation technique exhibited the best EE. The preparation conditions of the optimized NL were as follows: X1=200 mg; X2=7∶1; X3=20 times; X4=50 times; X5=1∶4; X6=30∶1. The verification test showed that the EE, the mean particle size and the span of the liposome were (42.5?1.3)%, (210.9?2.1) nm and (0.61?0.12), respectively. CONCLUSION: NL was prepared successfully.