芪月降脂片制剂处方的优化

[目的 ]优化芪月降脂片的制剂处方 .[方法 ]采用正交设计和多指标综合评分法对已筛选出的药剂辅料进行处方优化 .[结果 ]最佳制剂处方为糖粉 50 g ,辅料X 50g ,微晶纤维素 75g .[结论 ]该处方合理 ,成型性好     

Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

A pharmacokinetic comparison of the corn oil versus microemulsion gelcap formulation of cyclosporin used de novo after renal transplantation

The initial poor absorption of the corn oil-based, gel capsule oral formulation of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive therapy. Insufficient drug concentrations during the early post-transplant period predispose to renal allograft rejection. The present study served to compare the time required to achieve therapeutic CyA concentrations after de novo administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after renal transplantation, patients underwent serial pharmacokinetic profiling from which we obtained observed and dose-corrected values of several parameters. Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed the drug during days 0–2, from day 3 to 4 patients in the CyA-ME group showed significantly greater absorption than those in the CyA-GC group (P = 0.041). Patients in the CyA-ME group reached the 1st month target average concentration (C_av) values ( ≥ 550 ng/ml) earlier than those in the CyA-GC group and required significantly lower daily CyA doses (P = 0.018). We conclude that therapeutic CyA levels can be achieved more rapidly and with lower doses of the drug after de novo administration of CyA-ME than with CyA-GC. Received: 13 September 1996 Accepted: 7 January 1997     

Relative bioavailability of four controlled-release nifedipine products

Four controlled-release nifedipine products were investigated in two clinical studies. In study 1, 22 healthy male volunteers took part in an open, multiple-dose, randomized, crossover study to determine the relative bioavailablity of two 10 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer), administered 12 hourly, and one 20 mg controlled-release nifedipine tablet (Adalat® Retard, Bayer) administered 12 hourly. In study 2, 24 healthy male volunteers took part in an open, multiple-dose, randomized, three-period, crossover study to determine the relative bioavailability of (i) two 30 mg nifedipine gastro-intestinal therapeutic system (GITS) tablets (Adalat® XL, Bayer) administered once daily; (ii) one 60 mg nifedipine GITS tablet (Adalat® XL, Bayer) administered once daily; and (iii) one 20 mg plus one 10 mg nifedipine controlled-release tablet (Adalat® Retard, Bayer), administered 12 hourly. In both studies detailed pharmacokinetic data, in particular with respect to the controlled-release characteristics of the different formulations, were collected. Results of both studies indicate that all nifedipine products investigated are bioequivalent with respect to the extent of absorption of nifedipine. The nifedipine GITS products (Adalat® XL) have better controlled-release properties than the Adalat® Retard product, and are suitable for once-a-day administration.     

Arsenic trioxide–loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.     

Fiber Matrix Descriptors from Permeability Data Without Requiring Membrane Thickness: Theory,Results, and Optimization

Objective: Permeability of basement membrane and all other barriers contains a term for membrane thickness (Δx). This naturally leads to development of methods for measuring Δx that are imprecise, inaccurate, expensive, subject to preparation artifact, and inattentive to variability. Although height and shape of permeability (P) vs. probe radius (α) curves are sensitive to Δx, ln(P) or ln(P/free diffusivity or D_o) curves have shapes independent of Δx. It should, thus, be possible using such characteristics to determine fiber radius (r_f) and void volume ratio (ε) without Δx. We developed such a method to derive membrane structure by the standard model of Ogston and present its experimental evaluation. Methods: Basement membranes were self-assembled using 1: 1 Matrigel: 0.01 M Tris/150 mM NaCl/1.0 mM CaCl₂ buffer on 0.4-μ polycarbonate supports with transport measured in diffusion chambers using FITC-labeled hydroxyethyl starch probes from 25 to 102 Å in radius. Sampling was at 0.5 hr and then for each hour up to 5. Other membranes were measured 7 days after formation. Results: The best fit of the new technique occurred at 3 hr with R² = 0.949 ± 0.003 SEM, r_f = 36.8 ± 2.4 Å, and ε = 0.87 ± 0.02. Membranes studied for 7 days showed more variability but essentially the same characteristics. Conclusions: Membrane thickness is not necessary to reduce permeability of basement membrane to structure, and optimum sampling time is 3 hr.     

麦考酚酸酯及其临床应用进展

目的:麦考酚酸酯(MMF)是一种新型的免疫抑制剂.在临床应用中,MMF的使用也越来越广泛,已不仅仅局限于器官移植,还涉及到系统性红斑狼疮(SLE)、自体免疫风湿性疾病的治疗,以及在糖尿病,肺部血管高压的辅助治疗等诸多方面.肠包衣麦考酚酸钠,是一种新的可抵抗胃溶作用的麦考酚酸肠包衣剂型,药物在肠内释放,可以降低胃肠道(GI)不良反应的发生.     

肾移植术后普通环孢素A与环孢素A微乳剂对移植肾功能影响的系统评价

目的评价肾移植术后普通环孢素A与环孢素A微乳剂对受者移植肾功能影响的差异。方法遵循Cochrane肾脏协作组随机对照试验检索策略，检索MEDLINE（1994—2006．3）、EMBASE（1994～2006．3）、中国生物医学文献数据库CBM（1994—2006．3）、Cochrane图书馆（2005年第4期）与肾移植相关的8种中文杂志。采用Revman4．2．7进行Meta分析。结果共有5个随机对照试验纳入研究，包括1671例同种异体尸体肾移植患者。结论肾移植术后使用普通环孢素A与环孢素A微乳剂相比受者移植肾功能无明显差异，但环孢素A微乳剂肾毒性发生率较高。