HPLC测定草乌与贝母配伍后乌头碱类成分含量的变化

目的探讨生草乌与贝母不同配比在煎煮过程及体外模拟消化环境中乌头碱类成分的变化规律。方法采用HPLC法,测定生草乌与浙贝母不同配比水煎液及其经人工胃、肠液解离后的溶液中乌头碱及其水解产物焦乌头碱、苯甲酰乌头碱和苯甲酸的含量。结果除草乌贝母(2∶1)合煎液外,草乌贝母不同配比合煎或单煎后混合溶液中乌头碱的含量均较草乌单煎液明显提高。经人工胃肠液处理后各配伍液中乌头碱类成分的含量明显降低,但水解产物焦乌头碱、苯甲酰乌头碱与乌头碱的构成比较处理前明显提高。结论草乌与贝母一定比例下的配伍,毒性成分明显增大,证实了"草乌反贝母"的科学性。     

盐酸美金刚胺前药MeN-1和MeN -2在人工胃肠液中的稳定性研究

考察盐酸美金刚胺前药MeN -1和MeN -2在人工胃肠液中的稳定性.方法采用HPLC法测定盐酸美金刚胺前药MeN -1和MeN -2在人工胃液和人工肠液中的浓度,并比较两者的稳定性.结果MeN -1在人工胃液中孵育3h后,其相对含量为90％,但在人工肠液中降至约70％;而MeN -2在人工胃肠液中孵育1h后,其相对含...     

基于均匀设计的诃子制草乌特征性成分对H9c2心肌细胞毒性的影响

摘要：目的:筛选诃子制草乌特征性成分中的主要毒性作用成分和减毒作用成分。方法:采用均匀设计法安排实验,3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐（MTT）法考察诃子制草乌中4种特征性成分的不同配比对H9c2心肌细胞存活率的影响;应用Data Processing System（DPS）数据处理软件,对不同配比的细胞存活率进行逐步回归并绘制等高线图,分析4种特征性成分对H9c2心肌细胞毒性的影响及交互作用关系;以细胞存活率、乳酸脱氢酶（LDH）漏出率、细胞核平均荧光强度、线粒体膜电位为指标进一步对分析结果进行实验验证。结果:4种指标性成分中,存在于草乌中的新乌头碱、苯甲酰新乌头原碱均可明显降低H9c2心肌细胞存活率,以新乌头碱对毒性的贡献更大;诃子中的没食子酸、鞣花酸均可提高模型组（新乌头碱+苯甲酰新乌头原碱）细胞存活率,且没食子酸的作用强于鞣花酸。从交互作用的程度来看,具有显著降低H9c2心肌细胞存活率的交互项为新乌头碱和苯甲酰新乌头原碱;而交互项新乌头碱和鞣花酸、苯甲酰新乌头原碱和没食子酸可明显提高H9c2心肌细胞存活率。实验证实,新乌头碱和苯甲酰新乌头原碱共同作用,与对照组相比,细胞存活率明显降低（P<0.01）,LDH漏出率和细胞核平均荧光强度增加（P<0.01）,线粒体膜电位降低（P<0.01）;在新乌头碱和苯甲酰新乌头原碱混合物中单独加入没食子酸或鞣花酸均可提高细胞存活率（P<0.01）,升高线粒体膜电位（P<0.05或P<0.01）,降低LDH的漏出和细胞核平均荧光强度（P<0.01）;同时加入没食子酸和鞣花酸,其毒性作用进一步减弱。结论:诃子制草乌中的新乌头碱和苯甲酰新乌头原碱均具有一定的心肌毒性,以新乌头碱对毒性的贡献更大,两者具有协同作用;没食子酸和鞣花酸均可降低由两种乌头碱类成分产生的毒性作用,以没食子酸的减毒作用贡献更大,两者具有协同作用。     

诃子制草乌的炮制工艺研究

目的 以乌头碱、新乌头碱和次乌头碱的含量为指标,优化得到诃子制草乌的炮制工艺;并尝试用特征图谱的方法,分析炮制品的质量.方法 建立测定草乌中3种乌头碱含量的HPLC法和测定草乌特征图谱的方法,根据《蒙药炮制学》中记载的工艺进行单因素、正交试验和验证试验,优化炮制工艺,同时,对生品和不同炮制品进行特征图谱的分析,考察相似...     

HPLC法测定强筋健骨丸中3种乌头原碱的含量

目的建立强筋健骨丸的含量测定方法。方法以君药制川乌、制草乌中苯甲酰乌头原碱、苯甲酰次乌头原碱及苯甲酰新乌头原碱为目标成分,采用HPLC法,色谱柱Ultimate XB-C_(18)(250mm×4.6mm,5μm);流动相:乙腈(A)-0.1mol·L~(-1)醋酸铵溶液(B);流速:1.0mL·min~(-1);检测波长:235nm。结果苯甲酰新乌头原碱、苯甲酰乌头原碱和苯甲酰次乌头原碱质量浓度分别在7.580～121.280(r_1=0.999 9),1.576～25.216(r_2=0.999 8)和7.732～123.712(r_3=0.999 9)mg·L~(-1)范围内线性关系均良好,回收率分别为100.1%,100.0%和99.8%,RSD值分别为0.8%,1.5%和0.6%。结论该方法结果准确、稳定、可靠,能用于强筋健骨丸中苯甲酰新乌头原碱、苯甲酰乌头原碱及苯甲酰次乌头原碱的含量测定,可有效控制产品质量。     

有毒中药的合理炮制与临床用药

有毒中药是一类特殊的药物，要充分发挥其作用，使有毒转化为无毒，必须通过医药两方面的协调配合，有的放矢地加以炮制，并在临床上根据其性味功效进行合理使用。本文将有毒中药分为5类进行分析，供同道参考。1含有毒生物碱类中药1．1乌头类中药川乌、草乌、附子等均系毛莨科植物，它们的主要成分均为剧毒的双酯类生物碱等，这些生物碱经浸泡和蒸煮等加工炮制可使酯键水解，成为毒性较弱的苯甲酰乌头胺与醋酸。苯甲酰乌头胺进一步水解可得毒性更弱的乌头胺与苯甲酸，从而降低其毒性。可见川乌、草乌、附子的毒性主要决定于双酯型乌头碱的水…     

制川乌HPLC特征图谱研究和6种酯型生物碱的含量测定

目的:采用高效液相色谱建立制川乌的特征图谱,并同时测定6种酯型生物碱的含量。方法:以苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、新乌头碱、乌头碱、次乌头碱为对照,采用Phenomenex Gemini C18柱(250 mm×4.6 mm,5μm),乙腈-0.04 mol.L-1醋酸铵溶液(氨溶液调pH=10.0)梯度洗脱,流速0.8 mL.min-1,检测波长235 nm进行试验,用国家药典委员会中药色谱指纹图谱相似度评价系统2004AB处理分析。结果:不同来源的制川乌特征图谱相似度高,但乌头碱、次乌头碱、新乌头碱含量差异较大。生川乌与制川乌特征图谱比较,相似度小于0.3。结论:制川乌特征图谱专属性强,可结合6种酯型生物碱的含量测定全面控制制川乌的质量,为规范川乌的炮制工艺,合理、安全地使用制川乌提供科学依据。     

诃子抑制草乌的排泄

目的基于药物代谢动力学的过程,研究诃子对草乌排泄的影响。方法将56只SD大鼠随机分成正常对照组、生草乌组、诃子组、制草乌组、草乌-诃子(3∶1)组和草乌-诃子(1∶1)组、草乌-诃子(1∶3)组,每组8只,其中空白对照组给予等容积量的0.05%的羧甲纤维素钠溶液,诃子组按诃子0.36 g·kg~(-1)的剂量给药,剩余组别按生草乌0.12 g·kg~(-1)的剂量给药。单次灌胃给药后,采用代谢笼收集不同时间点的尿液样本及粪便样本。胆汁样本的收集,乙醚麻醉后,对大鼠进行胆管插管,每间隔1 h收集胆汁样本,共收集12 h内的胆汁样本。结果草乌中乌头碱(AC)、新乌头碱(MA)和次乌头碱(HA)3种乌头碱主要经由肾排泄。各组中AC的累积排泄量顺序是生草乌组>草乌-诃子(1∶1)组>草乌-诃子(1∶3)组>草乌-诃子(3∶1)组>制草乌组,MA和HA则与之顺序相反。3种乌头碱的排泄半衰期的顺序是草乌-诃子(3∶1)组>草乌-诃子(1∶1)组>草乌-诃子(1∶3)组>生草乌组>制草乌组。3种乌头碱在24 h后排泄量基本不发生变化。制草乌组和草乌-诃子(3∶1)组与生草乌组比较有明显差异(P<0.05),基本不经过胆汁和粪便排泄。结论诃子对草乌的药动学过程中的排泄过程有影响,可以延长草乌在体内的作用时间,保持药效。     

草乌花及其煎煮液中二萜生物碱的电喷雾串联质谱研究草乌花及其煎煮液中二萜生物碱的电喷雾串联质谱研究

目的 对草乌花及其煎煮液中的二萜生物碱进行定性分析,说明煎煮前后化学成分发生的变化。 方法用注射泵自动进样,电喷雾离子阱串联质谱直接分析草乌花及其煎煮液中生物碱混合物。结果 在生草乌花中发现3个新生物碱,草乌花煎煮后其中的双酯型生物碱和三酯型生物碱都发生水解,前者水解为苯甲酰乌头原碱和乌头原碱类生物碱,后者水解为3-乙酰-乌头原碱类生物碱。结论 该法简便、快速、灵敏、特异性强,为乌头属植物煎煮液中的生物碱分析提供了新途径。     

草乌花及其煎煮液中二萜生物碱的电喷雾串联质谱研究

目的对草乌花及其煎煮液中的二萜生物碱进行定性分析,说明煎煮前后化学成分发生的变化. 方法用注射泵自动进样,电喷雾离子阱串联质谱直接分析草乌花及其煎煮液中生物碱混合物.结果在生草乌花中发现3个新生物碱,草乌花煎煮后其中的双酯型生物碱和三酯型生物碱都发生水解,前者水解为苯甲酰乌头原碱和乌头原碱类生物碱,后者水解为3-乙酰-乌头原碱类生物碱.结论该法简便、快速、灵敏、特异性强,为乌头属植物煎煮液中的生物碱分析提供了新途径.     

单纯补液对羊水指数改善的影响

目的探讨单纯静脉补液治疗对妊娠羊水指数(AFI)的改善效果。方法选取医院2014年1月至2018年6月AFI不大于80 mm的患者140例,分为羊水偏少(50 mm 0. 05);D组经静脉补液治疗后的AFI明显高于治疗前(P <0. 05),但较C组差异不明显(P> 0. 05)。结论静脉补液治疗对羊水偏少和羊水过少妊娠过程中的AFI改善无明显疗效。治疗过程中应该加强胎心监护,胎心正常者可不进行静脉补液。     

Fluid replacement

Appropriate fluid replacement is an essential component of trauma patient resuscitation. Once haemorrhage is controlled, the restoration of normovolaemia is a priority. In the presence of uncontrolled haemorrhage, aggressive fluid resuscitation may be harmful. The crystalloid-colloid debate continues, but existing clinical practice is more likely to reflect local biases and dogma rather than evidence-based medicine. Colloids vary substantially in their pharmacology and pharmacokinetics and the experimental findings based on one colloid cannot be extrapolated reliably to another. In the initial stages of trauma patient resuscitation, the precise fluid used is probably not important, as long as an appropriate volume is given. Later, when the microcirculation is relatively leaky, there may be some advantages to colloids such as hydroxyethyl starch. Hypertonic saline solutions may have some benefit in patients with head injuries. A number of haemoglobin solutions are under development but one of the most promising of these has been withdrawn recently. It is highly likely that at least one of these solutions will eventually become routine therapy for trauma patient resuscitation. In the mean time, contrary to traditional teaching, recent data suggest that a restrictive strategy of red cell transfusion may improve outcome in some critically ill patients.     

Fluid flow in distensible vessels

1. Flow in single vascular conduits is reviewed, divided into distended and deflated vessels. 2. In distended vessels with pulsatile flow, wave propagation and reflection dominate the spatial and temporal distribution of pressure, determining the shape, size and relative timing of measured pressure waveforms, as well as the instantaneous pressure gradient everywhere. Considerable research has been devoted to accessing the information on pathological vascular malformations contained in reflected waves. Slow waves of contraction of vessel wall muscle, responsible for transport of oesophageal, ureteral and gut contents, have also been modelled. 3. The pressure gradient in a vessel drives the flow. Flow rate can be predicted both analytically and numerically, but analytical theory is limited to idealized geometry. The complex geometry of biological system conduits necessitates computation instead. Initially limited to rigid boundaries, numerical methods now include fluid-structure interaction and can simultaneously model solute transport, thus predicting accurately the environment of the mechanosensors and chemosensors at vessel surfaces. 4. Deflated vessels display all phenomena found in distended vessels, but have additional unique behaviours, especially flow rate limitation and flow-induced oscillation. Flow rate limitation is widespread in the human body and has particular diagnostic importance in respiratory investigation. Because of their liquid lining, the pulmonary airways are also characterized by important two-phase flows, where surface tension phenomena create flows and determine the patency and state of collapse of conduits. 5. Apart from the vital example of phonation, sustained self-excited oscillation is largely avoided in the human body. Where it occurs in snoring, it is implicated in the pathological condition of sleep apnoea.     

计算流体动力学用于吸入制剂的研究进展

简要介绍了计算流体动力学理论及其软件用于吸入制剂研究的一般方法及新进展.     

Mechanistic Fluid Transport Model to Estimate Gastrointestinal Fluid Volume and Its Dynamic Change Over Time

Gastrointestinal (GI) fluid volume and its dynamic change are integral to study drug disintegration, dissolution, transit, and absorption. However, key questions regarding the local volume and its absorption, secretion, and transit remain unanswered. The dynamic fluid compartment absorption and transit (DFCAT) model is proposed to estimate in vivo GI volume and GI fluid transport based on magnetic resonance imaging (MRI) quantified fluid volume. The model was validated using GI local concentration of phenol red in human GI tract, which was directly measured by human GI intubation study after oral dosing of non-absorbable phenol red. The measured local GI concentration of phenol red ranged from 0.05 to 168 μg/mL (stomach), to 563 μg/mL (duodenum), to 202 μg/mL (proximal jejunum), and to 478 μg/mL (distal jejunum). The DFCAT model characterized observed MRI fluid volume and its dynamic changes from 275 to 46.5 mL in stomach (from 0 to 30 min) with mucus layer volume of 40 mL. The volumes of the 30 small intestine compartments were characterized by a max of 14.98 mL to a min of 0.26 mL (0–120 min) and a mucus layer volume of 5 mL per compartment. Regional fluid volumes over 0 to 120 min ranged from 5.6 to 20.38 mL in the proximal small intestine, 36.4 to 44.08 mL in distal small intestine, and from 42 to 64.46 mL in total small intestine. The DFCAT model can be applied to predict drug dissolution and absorption in the human GI tract with future improvements.     

创伤性休克的院前液体复苏策略

目的了解限制性液体复苏和传统治疗方法对创伤性休克患者康复率的影响。方法对我院120中心2002年9月-2006年8月收治的598例创伤性休克患者的治疗进行分析比较，其中2002年9月-2004年8月接受传统治疗的109例患者作为对照组，2004年9月-2006年8月收治的489例接受限制性液体复苏的患者为治疗组。结果治疗组489例，康复出院462例，死亡8例。对照组109例转入相关专科治疗，康复出院93例，死亡16例。治疗组康复率为94．48％，明显优于对照组康复率83．49％（P〈0．01）。结论限制性液体复苏能有效提高创伤性休克患者的康复率。     

P-Glycoprotein Attenuating Effect of Human Intestinal Fluid

Purpose. To evaluate the effect of human intestinal fluid (HIF) on P-glycoprotein (P-gp)-mediated efflux. Methods. HIF was obtained from eight healthy volunteers by duodenal aspiration. HIF was applied at different concentrations (0-75%) to the apical compartment of the Caco-2 system. Cyclosporin A (CsA) was used as a model compound for P-gp mediated efflux. Results. When the bidirectional transport of CsA across Caco-2 monolayers was assessed, a significant polarity in transport could be observed, the absorptive transport being much lower than the secretory transport. Inclusion of HIF resulted in a moderate increase of the absorptive transport, as well as a significant concentration dependent decrease of the secretory transport, without compromising the integrity of the monolayer. Interestingly, a possible gender difference could be detected as inclusion of HIF obtained from female subjects resulted in a decreased absorptive transport of CsA, whereas inclusion of HIF obtained from male subjects resulted in an increased absorptive transport. The P-gp modulating effect of HIF is not caused by a lack of glucose as an energy source for the efflux mechanism when high concentrations of HIF were present in the buffer used. Conclusions. The results of this study indicate that the contribution of P-gp efflux carriers may be overestimated when using salt buffer solutions as transport media. Additionally, it can be concluded that (presently unidentified) components of HIF may attenuate the P-gp mediated intestinal efflux. The clinical significance of this modulating effect remains to be investigated.     

腹膜透析液中头孢西丁钠的稳定性考察

目的:考察注射用头孢西丁钠在25℃和37℃的腹膜透析液中的稳定性。方法:采用高效液相色谱法测定配伍液中头孢西丁钠的质量,并考察配伍液外观和pH值的变化。结果:头孢西丁钠与腹膜透析液配伍后8h内其外观、pH值及其质量均无明显变化。结论:头孢西丁钠在25℃和37℃的腹膜透析液中是稳定的;临用前须将腹膜透析液的温度温至37℃后再加入头孢西丁钠,以减少高温下头孢西丁钠的降解,确保安全用药。     

超临界流体色谱法分离手性药物

综述了超临界流体色谱在手性药物分离方面的研究和应用，介绍了超临界流体色谱手性分离的分离方式、色谱装置及操作条件。超临界流体色谱是一种很有潜力的色谱分离技术，具有高效、快速等特点，可以有效地弥补高效液相色谱和气相色谱在手性药物分离方面的不足。