愈骨疗伤片的处方筛选及制备工艺研究

  目的：优化愈骨疗伤片的制备工艺,筛选最优制剂处方。  方法：在考察提取物粒径基础上,以片剂中川续断皂苷溶出量作为考察指标,采用正交试验对搅拌速度、制粒速度和聚维酮K30浆液浓度三者关系进一步考察。采用单因素进一步优选润滑剂和包衣工艺条件。  结果：最佳的愈骨疗伤片处方为提取物颗粒中加入10%乳糖、7.5%羧甲基淀粉钠和2.5%聚维酮K30,以及0.5%硬脂酸镁混合后压片；采用低浓度乙醇包衣液进行包衣。  结论：制得的愈骨疗伤片制剂工艺稳定,包衣后改善了片剂的吸潮性,增加了产品的稳定性,更便于保存和运输。     

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

MED治疗腰椎间盘突出症时对神经根变异的探查

目的：观察显微内窥镜下椎间盘切除术（microendoscopic discectomy，MED）治疗腰椎间盘突出症时神经根变异情况，防止出现术中神经根损伤。方法：回顾分析自1999年10月至2003年12月应用MED治疗的腰椎间盘突出症患者724例，其中男452例，女272例。对术中发现存在腰骶神经根变异患者的临床特点及术中所见进行统计分析。结果：724例腰椎间盘突出症患者有37例神经根变异，发生率为5.1％。与术前的临床表现吻合，全部神经根变异患者均在MED下完成手术，无一例出现神经根损伤。结论：仔细探查及分离突出髓核周围神经根发出情况．确定有无神经根变异是防止MED治疗腰椎间盘突出症时发生神经根损伤的重要环节之一。     

Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

环化酶激活剂对大鼠感觉神经元保护作用的实验研究

目的探讨环化酶激活剂（前列腺素E1、腺苷及Zn^2＋离子）对周围神经损伤后感觉神经元的保护作用.方法在大鼠坐骨神经夹毁模型术后21 d,取背根节用图像分析法观测前列腺素E1（PGE1）、腺苷（Ade）和高Zn^2＋饲料（Zn^2＋）对背根节细胞数、核偏心率及核等圆径的影响,并与人胎盘神经生长因子（hNGF）的作用相比较.结果NGF及环化酶激活剂组与夹毁对照组相比都能增进背根节细胞的存活和减轻核偏移（P＜0.05）;NGF组和高Zn^2＋饲料组在背根节细胞存活数、核偏心率及核等圆径方面与假手术组无差别（P＞0.05）.结论PEG1、Ade及Zn^2＋离子等环化酶激活剂对DRG神经元均有保护作用,其中Zn^2＋离子的保护效应与NGF无差别.     

大鼠骶髂关节传入神经通路的实验研究

目的:通过逆行神经追踪法研究大鼠骶髂关节的传入神经通路。方法:30只雄性Sprague-Dawley大鼠随机分成非交感神经切除组(A组)和交感神经切除组(B组),每组15只,交感神经切除组切除左侧L1以下椎旁交感干。两组左侧骶髂关节注入30%的辣根过氧化物酶(HRP)20μl,72h后取出双侧的L1-S1背根神经节(DRG),TMB法染色后在光学显微镜下观察HRP阳性神经元细胞并计数。结果:两组左侧L1、L2背根神经节内HRP阳性神经元差异有显著性意义(P<0·05),B组HRP阳性神经元明显减少;左侧L3-S1背根神经节内HRP阳性神经元差异无显著性意义(P>0·05)。结论:L1-S1神经节含有支配同侧骶髂关节的传入神经元,同侧椎旁交感干可能是骶髂关节到L1-L2神经节重要的传入神经旁路,而不是到L3-L5神经节的传入旁路或重要的传入旁路。