钩藤碱微透析探针回收率测定及影响因素研究

目的:考察体内外微透析探针回收率的稳定性和重现性,为进一步的体内微透析试验提供依据。方法:采用增量法和减量法考察浓度、流速对探针回收率的影响。结果:微透析探针回收率受流速影响较大,基本不受浓度影响,且体内回收率稳定性良好。结论:微透析技术可用于钩藤碱的体内药代动力学研究,反透析法可作为体内研究钩藤碱探针回收率的测定方法。     

头孢拉定微透析体外回收率及影响因素的研究

目的 测定头孢拉定微透析体外回收率及影响因素。方法 采用微透析浓度差法（减量法、增量法）和液质联用技术（LC-MS/MS）测定头孢拉定的体外回收率,并考察流速、浓度对回收率的影响,以探讨微透析技术用于头孢拉定体内药动学研究的可行性。结果 所建立的方法在要求范围内线性关系良好,方法灵敏可靠。增、减量法测得的回收率无显著性差异。相同条件下,探针体外回收率随流速增大而减小,不受探针周围药物浓度的影响。结论 微透析技术可用于头孢拉定药动学研究,减量法可用于头孢拉定微透析体内回收率和药动学参数的测定。     

微透析法测定青藤碱大鼠体外血浆蛋白结合率

微透析法（microdialysis，MD）是新型药物动力学采样方法，可在活体动物身上进行实时（realtime）、动态（dynamic state）采样，所采集的样品不需前处理可直接进样分析。但此法对于高分子量、高蛋白结合率和高脂溶性的药物不适宜进行药物动力学研究。青藤碱是一种具有抗风湿活性的弱亲脂性生物碱，为了采用微透析法研究青藤碱的大鼠药物动力学行为，有必要测定大鼠的体外血浆蛋白结合率来评价体内微透析采样的可行性。     

提高微透析探针回收率方法的研究进展

微透析是将灌流取样和透析技术结合起来的研究物质动态变化的一种新型采样技术,适合于深部组织和重要器官的活体研究。微透析探针的回收率是影响微透析结果准确性的重要因素之一。微透析探针对物质的回收率通常较低,需结合灵敏的检测方法才能实现物质的定量分析,因此限制了微透析技术在科研中的应用及发展。如何提高微透析探针的回收率是亟待解决的问题,本文综述了国内外研究中提高微透析探针对物质回收率的方法,为探针回收率的提高提供一些参考。     

黄柏生物碱膝关节微透析探针回收率的测定

目的建立反相高效液相色谱法测定三妙丸中黄柏生物碱微透析探针体内外回收率,考察回收率影响因素及体内稳定性。方法采用增量法和减量法,用RP-HPLC法测定微透析样品中药根碱、巴马汀和小檗碱的质量浓度,考察流速及质量浓度对探针回收率的影响;探针分别植入颈静脉和膝关节,考察生物碱体内回收率稳定性。结果药根碱、巴马汀和小檗碱的质量浓度在0.04¹.0 mg·L-1内与峰面积呈良好的线性关系(r=0.999 8,n=7),本方法的专属性、精密度、准确度和稳定性等均符合微透析样品的分析要求。膝关节探针以1.0μL·min-1灌流,药根碱、巴马汀和小檗碱的相对回收率(RR)和损失率(RL)分别为(29.38±2.02)%和(31.80±1.88)%、(30.48±1.93)%和(30.93±2.09)%及(28.95±0.94)%和(30.53±1.74)%。在质量浓度为0.201.0 mg·L-1内与峰面积呈良好的线性关系(r=0.999 8,n=7),本方法的专属性、精密度、准确度和稳定性等均符合微透析样品的分析要求。膝关节探针以1.0μL·min-1灌流,药根碱、巴马汀和小檗碱的相对回收率(RR)和损失率(RL)分别为(29.38±2.02)%和(31.80±1.88)%、(30.48±1.93)%和(30.93±2.09)%及(28.95±0.94)%和(30.53±1.74)%。在质量浓度为0.20⁰.80 mg·L-1内,RR和RL一致,探针回收率与流速成反比,与质量浓度无关。体内回收率在5 h内保持稳定。结论反透析法校正大鼠血和膝关节的回收率时,所用的微透析方法可用于三妙丸中黄柏生物碱体内药动学研究。     

青藤碱微乳处方及其透皮性能研究

 目的：筛选青藤碱微乳最佳处方,同时考察不同体系的微乳体外透皮能力。方法：以大鼠离体皮肤渗透速率及累积渗透量为指标,采用均匀设计法确定最佳处方。结果：最佳处方为：聚山梨酯-20与乙醇为1∶2,含青藤碱2%,油酸2%,混合表面活性剂50%,水46%。结论：优选处方的青藤碱微乳透皮性能良好。     

青藤碱游离碱凝胶体外经皮渗透特性研究

目的:研究凝胶中青藤碱游离碱的体外经皮渗透特性。方法:采用改良的Franz扩散池法考察经皮渗透性能,以离体大鼠皮肤为经皮渗透屏障,通过高效液相色谱法测定药物含量。结果:青藤碱游离碱的经皮渗透速率常数(J值)为(20.3±3.89)μg·cm-2·h-1,是盐酸青藤碱J值的4.72倍。5%含量的2-吡咯烷酮可以抑制青藤碱游离碱的经皮渗透(P<0.05),而5%含量的磷脂、油酸、薄荷醇、柠檬烯和氮酮均增加青藤碱游离碱的经皮渗透,分别达1.37、2.25、3.71、6.75和10.15倍。结论:青藤碱游离碱较其盐酸盐具有优良的经皮渗透性能,更加适合青藤碱透皮新制剂开发。     

青藤碱微乳与凝胶的皮肤渗透性比较

目的比较青藤碱微乳和凝胶对离体大鼠皮肤的透皮能力。方法以油酸-聚山梨酯-80-无水乙醇-水作为微乳的组成,采用改进的Franz扩散池研究青藤碱微乳和凝胶的透皮行为,用高效液相色谱法测定青藤碱浓度。结果青藤碱微乳的透皮速率大于青藤碱凝胶(P<0.01),青藤碱微乳平均透皮速率为116.44μg.cm-2.h-1,青藤碱凝胶为89.93μg.cm-2.h-1。结论青藤碱微乳有很强的透皮能力,有望成为青藤碱的新型透皮给药制剂。     

高效液相色谱法测定青藤碱微乳的含量

［摘要］目的建立高效液相色谱（HPLC）法测定青藤碱微乳的含量.方法 色谱柱：ASM-Kromasil-C₁₈（4.6 mm×200 mm,5 μm）;流动相：0.5%三乙胺溶液-0.2%冰醋酸-乙腈（41.5：41.5：17.0）;检测波长：262 nm. 结果 青藤碱线性范围11～110 μg·mL^-1,平均回收率为99.33%,RSD为0.91%. 结论 该方法可靠,重复性好,可用于该制剂的质量控制.     

青藤碱电致孔给药的药动学及在关节腔中浓度的研究

目的比较电致孔与电加热条件下热敷给药时青藤碱在兔血液中的药动学及其在关节腔液中的浓度。方法在兔关节处分别进行电致孔和电加热热敷给药,给药后利用微透析技术收集关节腔透析液,同时通过耳缘静脉采血。串联质谱法测定血液及关节腔透析液中青藤碱浓度。DAS软件处理分析血药浓度数据,t检验分析关节腔透析液数据。结果电致孔给药组的AUC 0^∞为(3 915.0±537.7)ng·min·mL-1,是电加热给药组的2倍;Cmax为(29.3±4.9)ng·mL-1,是电加热给药组的2.5倍;tmax为(30.8±6.4)min比电加热给药组缩短20 min。电致孔给药时青藤碱在关节腔中的浓度是电加热给药的1.6∞为(3 915.0±537.7)ng·min·mL-1,是电加热给药组的2倍;Cmax为(29.3±4.9)ng·mL-1,是电加热给药组的2.5倍;tmax为(30.8±6.4)min比电加热给药组缩短20 min。电致孔给药时青藤碱在关节腔中的浓度是电加热给药的1.6⁶.9倍。结论电致孔与电加热给药相比增加了青藤碱入血的量,提高了青藤碱生物利用度,同时能让更多的青藤碱分布于关节腔局部。     

Enhancement of in vitro and in vivo microdialysis recovery of SB-265123 using Intralipid and Encapsin as perfusates

This study was conducted to compare the ability of two potential microdialysis perfusates to enhance the recovery of SB-265123, a lipophilic, highly protein-bound compound, both in vitro and in vivo. Initial in vitro experiments established that the recovery of SB-265123 by microdialysis using normal saline as a perfusate was poor (1.7%). Different concentrations of Intralipid and Encapsin also were evaluated in an identical in vitro setting, to determine enhancement of recovery. In vitro recovery was enhanced to approximately 24 and 65% with 5 and 20% Intralipid, and to approximately 59 and 62% with 5 and 20% Encapsin, respectively. A rat in vivo study was conducted with 20% Encapsin to confirm the in vitro observations. In the in vivo study, 75-80% recovery of free SB-265123 was achieved using 20% Encapsin as a perfusate. The results from this study indicate that for SB-265123, a lipophilic, highly protein-bound molecule, Encapsin is an efficient recovery enhancer in vitro. The results from this investigation further demonstrate that a recovery enhancer may be useful for in vivo applications, even with a compound that is highly bound to plasma protein.     

微透析技术探针回收率的影响因素研究进展

微透析技术是近年来发展起来的动态生物取样技术,具有"活体、微创、实时、高效"等特点,其与现代分析技术联用,实现了连续取样和动态测定,可进行微量的定性、定量分析。微透析探针回收率的准确校正,是测定生物体中待测组分确切浓度的关键步骤,可提高大分子、难溶性物质的回收率,使微透析的应用更为广泛。本文对微透析探针回收率的影响因素、校正方法以及近年来提高回收率所取得的进展做一综述。     

葛根素微透析线性探针相对回收率影响因素的研究

目的考察影响葛根素微透析相对回收率相关影响因素,探索提高微透探针相对回收率的方法。方法采用高效液相色谱法考察不同pH值（5.1、6.0、7.4、8.1）,不同浓度丙二醇（1%、5%、10%、20%、30%）,不同浓度羟丙基-β-环糊精（1%、5%、10%、20%）的灌注液对葛根素微透析线性探针相对回收率的影响。结果微透析灌注液pH值5.1,羟丙基-β-环糊精含量5%时,葛根素相对回收率提高至（90.07±1.24）%。灌流液中丙二醇会对微透析线性探针的传递率产生负影响,降低相对回收率,在以葛根素为模型药物的微透析实验灌流液中不建议添加。结论本实验方法灌流液中添加增溶剂羟丙基-β-环糊精,可使葛根素经过半透膜时流失量减少,显著提高葛根素微透析线性探针相对回收率。     

反向透析法用于体内经皮吸收微透析探针回收率的测定

目的考察反向透析法用于体内经皮吸收过程中微透析探针回收率校正的可行性.方法在体外试验中用零净流量法测定探针的回收率和传递率,在体内试验中用反向透析法测定探针的回收率;以小猪为试验动物,观察模型药雷公藤内酯醇软膏的体内经皮吸收过程.结果体外试验中,微透析探针的回收率为(64.29±2.34)%,回收率和传递率一致;体内经皮微透析实验中探针的回收率在实验前为(51.47±3.51)%,实验结束后为(51.96±4.97)%.雷公藤内酯醇软膏经皮吸收后,药物在皮内浓度很快达到稳态,去除药物后皮内药物浓度则迅速下降.结论反向透析法测定的探针回收率在实验过程中稳定,可以用于测定体内经皮吸收微透析探针回收率.     

In vitro recovery of triamcinolone acetonide in microdialysis

The purpose of this study was to assess the factors affecting the calibration of the microdialysis probe for the in vitro recovery of triamcinolone acetonide (TA). Recoveries of TA were determined in microdialysis, retrodialysis, and no-net flux methods. Experiments were performed at room temperature or 37 degrees C while the reservoir medium was either stirred or unstirred. The effect of the viscosity of the medium on the recovery was studied using methylcellulose gel spiked with TA. Recovery was also calculated by the no-net-flux method in Ringer's solution and in plasma. Stirring the medium increased the recovery of TA by 30%. The recovery was higher at 37 degrees C under stirred or unstirred conditions and was same in either direction of dialysis. Increasing viscosity of the reservoir medium decreased the recovery (55% in Ringer's solution to 14% in 20% methylcellulose gel). Recovery from spiked plasma under stirred conditions was only 15% and this shift which was also seen in no-net-flux method was accounted for by the protein binding. Binding of TA, determined by ultrafiltration, was 20% in 5% gel and 81% in plasma. The recovery determined by the no-net-flux method was similar to the retrodialysis result. Stirring, temperature, viscosity and protein binding in the reservoir medium affected the in vitro recovery of TA.     

Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine

The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box–Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (J_ss) of SIN from PLO was 146.55?±?2.93?μg/cm²/h, significantly higher than that of gel (120.39?μg/cm²/h) and the amount of SIN deposited in skin from the PLO was 10.08?±?0.86?μg/cm², significantly larger than that from gel (6.01?±?0.04?μg/cm²). In vivo skin microdialysis studies showed that the maximum concentration (C_max) of SIN from PLO in “permeation study” and “drug-deposition study” were 150.27?±?20.85?μg/ml and 67.95?μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73?μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.     

微透析技术在皮肤药理学中的应用进展

微透析是一种活体的取样技术,在皮肤药理学的研究中应用广泛。微透析被用于外用制剂的生物等效性、制剂的透皮吸收、监测皮肤炎症介质、皮肤组织的内分泌、中药经皮代谢等相关研究。近年来,微透析向联用各种分析检测技术的方向发展,如联用超高效液相色谱、液质联用、酶标记免疫吸附测定等。然而,该技术本身也存在一些缺点,如油水分配系数较大药物的测定、低含量药物的测定、探针植入重现性等问题。文中综述了该技术的原理、优点、缺点及在皮肤药理学研究中的应用进展。