蒙药绿松石的质量标准研究＊

目的 建立蒙药绿松石的质量标准。方法 收集不同产地绿松石，共10批。观察绿松石样品和粉末的性状并进行理化鉴别；按2020年版《中国药典》（四部）通则方法测定绿松石样品中水分、浸出物含量；采用原子吸收光谱法测定绿松石样品铜元素含量。结果 绿松石为不规则、周围带有黑石的块状物，表面蓝绿色，体重，质硬脆，难砸碎，断面呈贝壳状，蜡样光泽，粉末呈灰绿色，无臭，味淡；理化鉴别结果显示，呈铜盐反应；10批次样品中水分含量为0.41%-3.94%（SD=1.37%），浸出物含量为0.21%-0.81%（SD=0.21%），铜元素含量为3.03%-4.63%（SD=0.63%）。结论 初步拟定绿松石中水分含量不得超多5.0%、浸出物含量不得低于0.10%，铜元素含量应为2.60%-4.84%，制定的标准可用于蒙药材绿松石的质量控制。     

Population pharmacokinetics of tanezumab in phase 3 clinical trials for osteoarthritis pain

AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V ₁), peripheral volume (V ₂), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day^–1, 2.71 l, 1.98 l, 0.371 l day^–1, 8.03 μg day^–1 and 27.7 ng ml^–1, respectively. Inter‐individual variability (IIV) was included on CL, V ₁, V ₂ and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V ₁ and V ₂ significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit.     

优克龙治疗输尿管结石(附60例报告)

目的　观察优克龙 (Urocalun )治疗输尿管结石的疗效和安全性。　方法　对 6 0例输尿管结石直径 <1cm的患者予口服优克龙治疗 ,4 5 0mg/次 ,3次 /d ,服药 5周。　结果　 6 0例患者中结石排出 4 5例 (75 % ) ;10例 (17% )结石位置下降 ;5例 (8% )位置无变化。 4例患者服药后有轻度胃部不适、恶心或口干。　结论　优克龙治疗输尿管结石效果良好。     

Block of potassium channels and facilitation of acetylcholine release at the neuromuscular junction by the venom of the scorpion, Pandinus imperator

Venom from the scorpion Pandinus imperator potently and selectively blocks voltage-gated K+ channels in bullfrog neurones (Pappone, P. A. and Cahalan, M. D. 1987, J. Neurosci. 7, 3300-3305). Its effects on neuromuscular transmission have now been assessed. Twitch tension studies on chick biventer cervicis preparations showed that the venom (1 microgram/ml and above) significantly augmented responses to nerve but not muscle stimulation; there was little change in postjunctional sensitivity to cholinoceptor agonists or K+-induced depolarization. Electrophysiological studies on mouse triangularis sterni preparations revealed that the venom had no effect on spontaneous transmitter release, but increased evoked transmitter release. Extracellular recordings of nerve terminal action potentials showed that the venom selectively reduced the component of the waveform associated with K+ currents. These results confirm that this venom can selectively block neuronal K+ currents, and they show that this can facilitate the release of acetylcholine at the neuromuscular junction.