喷他佐辛压敏胶分散型贴剂的制备研究

目的研制喷他佐辛压敏胶分散型贴剂并考察其体外经皮渗透性。方法将喷他佐辛及各种促渗剂直接溶于压敏胶中制备压敏胶分散型贴剂,采用卧式双室扩散池,研究其体外经皮渗透行为。结果由Duro-Tak 87-9301型压敏胶制备的贴剂具有较好的稳态渗透速率。5%氮酮与10%豆蔻酸异丙酯合用对喷他佐辛促渗效果明显,经皮渗透速率为(11.28±0.63)μg/(cm2.h),促渗倍率达3.01倍。贴剂中喷他佐辛的含量由2%增加到4%,经皮渗透速率明显增大,含量增加到6%和8%时渗透速率无明显变化。结论所得处方中各因素的组合有利于喷他佐辛的经皮吸收。     

基体辅助激光解吸质谱法在生物大分子质量研究中的应用

研究了基体辅助激光解析飞行时间质谱法(MALDI-TOF MS)测定蛋白和糖蛋白的实验条件,实测了重组人白细胞介素2、肿瘤坏死因子、粒细胞巨噬细胞集落刺激因子、白细胞干扰素α2b、白细胞干扰素α₁、促红细胞生成素、钙调蛋白及其片段、大鼠脑型一氧化氮合成酶和天然牛精液蛋白提取物的分子量和纯度,鉴定了蛋白质混合物中各单个成分,结果表明MALDI-TOF MS可有效地研究基因工程蛋白质和天然蛋白提取物等生物大分子的质量。     

高效液相色谱法测定金钱草胶囊中槲皮素的血药浓度

目的建立金钱草胶囊中槲皮素的血药浓度测定方法,为临床应用和药代动力学研究提供技术参考。方法采用高效液相色谱-紫外检测方法测定,色谱柱为Kromasil C8柱(250 mm×4.6 mm,5μm),流动相为甲醇-乙腈-0.4%磷酸溶液(40∶10∶50),流速1 mL/min,柱温30℃,进样量20μL,检测波长360 nm。血样提取方法,以β-葡萄糖苷酸酶水解后,以乙酸乙酯提取,氮气流吹干后复溶进样。结果槲皮素保留时间约为8.8 min,金钱草胶囊中槲皮素的血药浓度线性范围0.08～12μg/mL,最低定量限为0.05μg/mL,检测限为0.02μg/mL。方法平均回收率为97.50%～102.50%,水解提取回收率为76.46%～87.43%,日内精密度RSD为4.18%～6.17%,日间精密度RSD为5.08%～8.63%。结论方法简便,分析速度快,灵敏度较高,重复性好,适用于临床血药浓度测定及药代动力学研究。     

注射用促肝细胞生长素辅料的研究

寻找一种注射用促肝细胞生长素（ＨＧＦ）适用的辅料。方法：以三批不同批次的ＨＧＦ原料液为实验对象,分别通过 Ｆｏｌｉｎ－酚和~３Ｈ－ＴｄＲ掺入法研究了三种辅料： ３％右旋糖酐, ８％甘露醇, ２％右旋糖酐＋ ８％甘露醇对ＨＧＦ多肽含量及活性的影响。结果：８％甘露醇作为辅料时使ＨＧＦ多肽含量测定显著增高,而右旋糖酐则不影响测定结果。三种辅料对ＨＧＦ活性均无显著影响。结论：最终选用３％右旋糖酐作为ＨＧＦ的辅料。     

A novel approach to prepare tripolyphosphate/chitosan complex beads for controlled release drug delivery

A novel approach was developed to improve the mechanical strength of tripolyphosphate (TPP)/chitosan beads prepared under coagulation condition at 4 degrees C in the presence of gelatin. Cross-sectional analysis indicated that the beads had a homogeneous crosslinked structure, as a result the beads were strengthened greatly (the mechanical strength increased more than ten times). Furthermore sodium alginate (a polyanion) can interact with cationic chitosan on the surface of these TPP/chitosan beads to form polyelectrolyte complex film for the improvement of the drug sustained release performances. The loading efficiency of model drugs (brilliant blue and FITC-dextran) in these beads was very high (more than 90%). Crosslinking time, TPP solution pH and other preparation factors had an effect on the drug release performance of beads. The release period of brilliant blue (a poor water soluble dye) was more than 2-months at a fairly constant rate in 0.9% NaCl, 10 mM PBS pH 7.4. However, for FITC-dextran (a water soluble polysaccharide) only 1-2 days in the same conditions. It seems that TPP/chitosan bead prepared by the novel method is a promising formulation for drug delivery.     

氯吡格雷和沙格雷酯联用致血小板减少

1例74岁女性患者行人工血管旁路移植术,术后给予肝素,约8．33U·Kg^-1·min^-1静脉泵入;氯吡格雷50mg,1次／d口服;沙格雷酯100mg,3次／d口服;华法林3mg／d口服。手术次日停用肝素,改为达肝素钠0．4ml,1次／12h皮下注射。术后第7天血小板301×10^9／L,停用达肝素钠,同时加用辛伐他汀20mg／d,氯吡格雷、沙格雷酯及华法林按原剂量口服。术后6个月停用华法林,继续口服其他3种药物,此时复查血小板计数为240×10^9／L。术后9个月复查,血小板计数降至1×10^9／L,白细胞及血红蛋白水平正常。立即停用氯吡格雷和沙格雷酯,继续口服辛伐他汀。停药4周,血小板计数恢复至156×10^9／L。     

Inhibition of human Na(v)1.5 sodium channels by strychnine and its analogs

Strychnine and brucine from the seeds of the plant Strychnos nux vomica have been shown to have interesting pharmacological effects on several neurotransmitter receptors. In this study, we have characterized the pharmacological properties of strychnine and its analogs on human Na_v1.5 channels to assess their potential therapeutic advantage in certain arrhythmias. Among the eight alkaloids, only strychnine and icajine exhibited inhibition potency on the Na_v1.5 channel with the half-maximum inhibition (IC₅₀) values of 83.1 μM and 104.6 μM, respectively. Structure–function analysis indicated that the increased bulky methoxy groups on the phenyl ring or the negatively charged oxygen atom may account for this lack of inhibition on the Na_v1.5 channel. Strychnine and icajine may bind to the channel by cation–π interactions. The substitution with a large side chain on the phenyl ring or the increased molecular volume may alter the optimized position for the compound close to the binding sites of the channel. Strychnine and icajine bind to the Na_v1.5 channel with a new mechanism that is different from TTX and local anesthetics. They bind to the outer vestibule of the channel pore with fast association and dissociation rates at resting state. Strychnine and icajine had little effect on steady-state fast inactivation but markedly shifted the slow inactivation of Na_v1.5 currents toward more hyperpolarized potentials. The property of icajine influencing slow-inactivated state of Na_v1.5 channel would be potential therapeutic advantages in certain arrhythmias.     

注射用头孢哌酮钠-舒巴坦钠致严重迟发型过敏反应1例

1例72岁男性患者因右下肺感染入院,静脉滴注头孢哌酮钠-舒巴坦钠后出现严重迟发型过敏反应。通过对头孢哌酮钠-舒巴坦钠致不良反应的原因进行探讨,为临床合理用药提供参考。     

赖诺普利与依那普利对高血压的疗效比较

９２例原发性Ⅰ和Ⅱ期高血压病人采用随机、单盲方法，分２组治疗。一组用赖诺普利，ｐｏ，２０－８０ｍｇ／ｄ，另一组用依那普利，ｐｏ，１０－４０ｍｇ／ｄ，疗程均为４ｗｋ。降压总有效率和降压幅度：赖诺普利是８９％和２．９／２．０ｋＰａ，依那普利是９７％和３．１／２．１ｋＰａ，２药降压均显著（Ｐ＜０．０１），降压疗效相仿（Ｐ＞０．０５）。不良反应发生率是２９％和３４％，其中最多是干咳。结果提示赖诺普利治疗轻、中度高血压有效、安全。