Cholesteryl hemisuccinate as liposomal membrane stabilizer and its use in the preparation of saikosaponin-D liposomes / 药学学报

<p><b>AIM</b>To study the membrane stabilization effect and mechanism of cholesteryl hemisuccinate (CHEMS) on dipalmitoylphosphatidylcholine (DPPC) liposomes; Saikosaponin-D (SSD) liposomes were prepared by using CHEMS as a membrane stabilizer and its encapsulation efficiency and hemolytic activity were evaluated.</p><p><b>METHODS</b>Differential scanning calorimetry (DSC) and calcein release were used to study membrane stabilization effect of CHEMS on DPPC membrane, Fourier transform infrared spectroscopy (FT-IR) was used to study the interacting mechanism of CHEMS with DPPC, sedimentation experiment was done to study the interaction of CHEMS with SSD and hemolytic study was used to evaluate the hemolytic activity of SSD-liposomes with CHEMS as membrane stabilizer.</p><p><b>RESULTS</b>DSC analysis showed that CHEMS and cholesterol (CHOL) could all decrease the Tm value slightly and the deltaH value markedly. CHEMS was more effective than CHOL in decreasing the deltaH value of DPPC membrane. It suggested that CHEMS was more effective in increasing DPPC membrane stability. It was also proved by calcein release study carried out both in PBS and 30% plasma. The findings by FT-IR suggested that CHEMS has both hydrogen bond and electrostatic interaction with the polar head of DPPC. CHEMS did not form insoluble complex (INCOM) with SSD by sedimentation experiment. Stable SSD-liposomes were prepared using DPPC and CHEMS and decreased effectively the hemolytic activity of SSD, SSD-liposomes may be given intravenously at a concentration of 15 microg x mL(-1), while free SSD was forbidden to be given intravenously.</p><p><b>CONCLUSION</b>CHEMS was more effective than CHOL in increasing DPPC membrane stability, and it could be of great use in the preparation of cholesterol-dependent hemolytic saponins-liposomes. The hemolytic activity of SSD-liposomes was greatly reduced, allowing a possible concentration of 15 microg x mL(-1) to be intravenously administered.</p>

[First-line Xeloda (Capecitabine) treatment for advanced and recurrent colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of capecitabine as first-line therapy in patients with advanced and recurrent colorectal cancer. METHODS: From December 2000 to November 2001, sixty patients with advanced and recurrent colorectal cancer received first-line capecitabine treatment given at a dose of 1250 mg/m(2) twice daily, on days 1 - 14 every 21 days. At least 2 cycles were administered. RESULTS: The overall response rate was 23.3% with 14 PR, 24 SD (40.0%) and 15 PD. The median survival time was 14.7 months. The survival rate was 63.9% at 12-months and 33.4% at 24-months. Grade III-IV adverse effects were diarrhea in 4 patients (6.6%), anemia in 2 (3.3%) and hand-foot syndrome (HFS) in 1 (1.7%); Grade I-II adverse effects were hyperpigmentation in 20 (33.3%), HFS in 18 (30.0%) and diarrhea in 10 (16.7%). CONCLUSION: Capecitabine is an efficacious and better-tolerated alternative treatment for the patients with advanced and recurrent colorectal cancer.

Venovenous bypass ahead of mobilization of the liver in orthotopic liver transplantation.

BACKGROUND: To evaluate feasibility and safety of venovenous bypass prior to mobilization of the liver during orthotopic liver transplantation (OLT). METHODS: Fifty-four patients were classified into two groups. Group A consisted of 23 patients receiving OLT with classical venovenous bypass. Group B consisted of 31 patients who received a modified-procedure: venovenous bypass ahead of the mobilization of the liver during OLT. The blood loss, duration of venovenous bypass, cold ischemia time, anhepatic phase, and transfusion during operation in the two groups were compared. Complications after the operation were also compared between the two groups. RESULTS: The duration of venovenous bypass and cold ischemia time in group A were longer than those in group B [(99.78+/-21.36 min) vs (96.32+/-22.25 min) and (484.78+/-134.01 min) vs (443.15+/- 85.27 min)]. The anhepatic phase lasted for about 100 min averagely in the two groups. The volumes of blood loss and transfusion during the operation were larger in group A than in group B [(5096+/-4243 ml) vs (1726+/-1125 ml) and (3676+/-2938.74 ml) vs (1217.69+/-829.72 ml)]. Postoperative complications occurred in 26 patients of group A and in 19 patients of group B. CONCLUSION: This modified-procedure or venovenous bypass ahead of mobilization of the liver in OLT can reduce the blood loss during OLT and the incidence of postoperative complications without prolongation of the anhepatic phase and duration of venovenous bypass.

Studies on pulsatile release tablets of diltiazem hydrochloride in explosion way / 药学学报

<p><b>AIM</b>To investigate the preparation of pulsatile release tablets, the release of the drug in vitro and the pharmacokinetics in vivo.</p><p><b>METHODS</b>Diltiazem hydrochloride (DIL) was used as model drug. The pulsatile release tablets were prepared by film-coated method using ethylcellulose and Eudragit L. The effect of formulation on pulsatile release of diltiazem hydrochloride was investigated under release rate test. The mechanism of pulsatile release of drug was proved by the test of water-uptake. The pharmacokinetic and bioavailability study in eight human subjects was performed by HPLC method.</p><p><b>RESULTS</b>The release of diltiazem hydrochloride effected by the formulation of the core tablets and the composition and thickness of the coating film. In vitro, the delayed-release time T10 was 4.4 h, the maximum release time Trm was 8.0 h and the pulsed-release time Trm-10 was 3.6 h. In vivo, the delayed-release time Tlag was 4.9 h, the peak time was 8.0 h and the pulsed-release time was 3.1 h. The relative bioavailability was 105%.</p><p><b>CONCLUSION</b>The release of drug from pulsatile release tablets of diltiazem hydrochloride was shown to be in pulsed way both in vitro and in vivo.</p>