落新妇苷在小鼠体内的组织分布

目的 建立落新妇苷组织浓度的高效毛细管电泳分析方法,并对其在小鼠体内的组织分布进行测定.方法 高效毛细管电泳之胶束电动模式测定小鼠尾静脉注射30 mg/kg落新妇苷后不同时间点各组织中药物含量.结果 落新妇苷在组织器官的浓度分布特点是:C心＞C肝＞C肾＞C脾＞C肺＞C脑.心脏组织C5min＞C15min＞ C60min,自5 min浓度达峰后呈缓慢递减趋势,C60min仍保持较高浓度.其他组织C15min达峰,肝脏在C15min至C60mm均保持较高药物浓度,C60 min在各组织中浓度最高.60 min内脑组织含有较稳定药物含量.结论 落新妇苷在小鼠体内分布广泛,心、肝、肾保持较高组织浓度,且能够穿越血脑屏障分布到脑组织中.     

基于双波长融合HPLC图谱的银屑病外用方中7种活性成分定量分析

目的:测定银屑病外用方中7个主要活性成分(新落新妇苷、落新妇苷、新异落新妇苷、异落新妇苷、黄杞苷、异黄杞苷、柠檬苦素)含量。方法:采用Waters Xbrige BEH C₁₈色谱柱(150 mm×4.6 mm, 3.5μm),以水(A)-乙腈(B)为流动相,梯度洗脱(0～5 min, 17%B;5～10 min, 17%B→20%B;10～15 min, 20%B;15～25 min, 20%B→100%B),流速1.0 mL·min^-1,柱温30℃,进样量5μL,检测波长为292 nm(0～19 min,新落新妇苷、落新妇苷、新异落新妇苷、异落新妇苷、黄杞苷、异黄杞苷)、210 nm(19～25 min,柠檬苦素),使用MATLAB软件编程,对CSV格式数据进行双波长融合。结果:新落新妇苷、落新妇苷、新异落新妇苷、异落新妇苷、黄杞苷、异黄杞苷和柠檬苦素线性范围分别为39.06～1 250μg·mL^-1(r=0.999 9)、26.25～840μg·mL^-1(r=0.999 7)、18.64～59...     

4-邻甲基苯磺酰氧基苯并噁唑酮固体分散体的制备及其药代动力学研究

目的制备化合物4-邻甲基苯磺酰氧基苯并噁唑酮(MBB)固体分散体,以提高其溶出度;建立高效液相色谱法(HPLC)法测定MBB固体分散体在大鼠血浆的浓度,并进行初步的药代动力学研究。方法以聚乙烯吡咯烷酮PVPk30,PEG6000,PEG4000和泊洛沙姆188为载体,按照MBB与载体质量比为1∶5、1∶8、1∶10制备固体分散体,并测定其溶出度,绘制溶出曲线,以确定最佳固体分散体的制备处方;SD大鼠灌胃给予MBB固体分散体,采用HPLC法测定不同时间MBB在血浆中的浓度,绘制血药浓度曲线,利用计算机程序3p87进行房室模型拟合,计算药代动力学参数。结果当MBB与PVPk30的质量比为1∶8时,溶出度最高,为该固体分散体的最优处方;该分散体在大鼠体内的药代动力学符合一室模型,其AUC为123.39(μg·ml~(-1))×min,cl为0.41μg·ml·h(mg/kg),t1/2(ka)为8.48 min,t1/2(ke)为8.86 min。结论将MBB制成固体分散体,可显著提高其溶出度,且当MBB与PVPk30的质量比为1∶8时为最优处方;该固体分散体可显著提高MBB的血药浓度。     

依折麦布混悬剂的制备及药物动力学研究

目的制备依折麦布/介孔硅固体分散体,以该固体分散体制备混悬剂,研究固体分散体和三甲基壳聚糖(TMC)对依折麦布药物动力学的影响。方法采用溶剂挥发法制备依折麦布/介孔硅固体分散体,以溶出度为指标筛选制备方法,采用差示扫描量热(DSC)、扫描电镜(SEM)等技术考察药物存在状态及物理稳定性。以甲基纤维素和TMC分别为助悬剂,将依折麦布/介孔硅固体分散体制成混悬液,研究大鼠口服各混悬液的药物动力学。结果依折麦布与介孔硅质量比为1∶5,搅拌时间为6h,制得固体分散体的载药量为16.5%,药物以非晶状态存在,溶出度可达92.2%,AUC和Cmax提高显著,tmax无明显变化。结论应用该固体分散技术和三甲基壳聚糖能改善依折麦布的口服吸收,提高生物利用度。     

提高原人参二醇口服生物利用度的固体分散体及其片剂的制备与评价

目的 本文拟研究一种加水复溶后可转化为纳米混悬液的新型固体分散体片剂,提高原人参二醇（PPD）口服给药的溶解度和生物利用度。方法 通过将药物、聚合物载体和表面活性剂按10:14:6的比例溶解于乙醇后,减压真空干燥制备固体分散体,然后将固体分散体、乳糖、交联聚乙烯吡咯烷酮和硬脂酸镁按300:16:60:4的比例混合后,直接压成片重400 mg的片剂。结果 发现含泊洛沙姆188和维生素E聚乙二醇琥珀酸酯（TPGS）的原人参二醇固体分散体加水复溶后可转变为纳米混悬液。以乙烯基吡咯烷酮/醋酸乙烯共聚物64（PVP-VA）为载体,维生素E聚乙二醇琥珀酸酯为表面活性剂的固体分散体加水复溶后可转变为平均粒径小于120 nm的纳米混悬液,该混悬液放置8 h后粒径基本稳定。固体分散体经压制成片剂后可在15 min内溶出超过90%的药物,且其溶出的药物可稳定维持至少8 h。固体分散体经大鼠灌胃给药后,其最高血药浓度和生物利用度是原型药物及辅料物理混合物的6.59倍和2.54倍。结论 该研究表明可转化为纳米混悬液的固体分散体片剂是一种可提高原人参二醇口服生物利用度的新制剂方法。     

热熔挤出技术制备普罗布考固体分散体及其大鼠体内药动学研究

以Soluplus为载体,采用热熔挤出技术制备普罗布考固体分散体,并评价其平衡溶解度、溶出度及大鼠体内药动学行为.结果表明,普罗布考-Soluplus比例为1:3(w/w)的固体分散体,在30 min时的体外累积溶出率为97％.差示扫描量热和粉末X-射线衍射分析表明药物主要以分子状态分散于固体分散体中.大鼠体内药动学研究表明,普罗布考固体分散体的cmax和口服生物利用度是原药的3.26倍和3.02倍.     

葛根素固体分散体的制备及大鼠体内生物利用度研究

本文采用新型的固体分散体技术,将葛根素,磷脂与PVP制成固体分散体,对其理化性质进行研究,考察固体分散体在大鼠体内的药一时曲线,计算其在大鼠体内的药动学参数,并与葛根素原料比较,研究固体分散体的相对生物利用度。结果表明以磷脂和PVP为载体制备的固体分散体（药物-磷脂-PVP,2：4：1）的表观油水分配系数最好,固体分散体相对生物利用度较纯葛根素提高了2．53倍。     

黄芩苷磷脂复合物固体分散体的药动学研究

摘要：目的:研究黄芩苷磷脂复合物固体分散体在体内的药动学特征。方法:分别灌胃给予SD大鼠黄芩苷、黄芩苷磷脂复合物及其固体分散体,给药剂量为70 mg·kg-1。HPLC法测定黄芩苷血药浓度,绘制药-时曲线,DAS2.0计算药动学参数。结果:黄芩苷磷脂复合物固体分散体的平均达峰浓度Cmax为2.707μg·ml-1,较黄芩苷原料药的Cmax0.745μg·ml-1与磷脂复合物的Cmax2.219μg·ml-1,差异均具有统计学意义（P<0.05或P<0.01）;黄芩苷磷脂复合物固体分散体组AUC0-t27.182 g·h·ml-1,较黄芩苷原料药的AUC0-t7.673 g·h·ml-1与磷脂复合物的AUC0-t20.188 g·h·ml-1,差异均具有统计学意义（P<0.05或P<0.01）。结论:黄芩苷磷脂复合物制备成固体分散体后,黄芩苷口服生物利用度得到进一步提高。     

姜黄素固体分散体在小鼠体内的药代动力学

目的以姜黄素混悬液为对照,研究姜黄素-聚维酮固体分散体灌胃给药后在小鼠体内的药代动力学。方法按300mg·kg-1的剂量小鼠灌胃姜黄素固体分散体溶液或姜黄素混悬液,采用高效液相色谱法测定血浆中姜黄素含量,用DAS软件拟合房室模型,计算药动学参数。并测定了给药3h时药物的吸收率。结果姜黄素-聚维酮固体分散体在小鼠体内的药代动力学符合二室开放模型,主要药动学参数如下:T12α和T12β分别为16.4和266min,AUC为89.6mg·mL-1.min-1,Vd为763.9L,V1为51.0L,CL为1.99L·min-1。姜黄素-聚维酮固体分散体在胃肠道的吸收率是姜黄素混悬液的6.75倍。结论姜黄素固体分散体灌胃可显著增加姜黄素的生物利用度,血药浓度较高。     

固体分散体制备工艺对其物理稳定性的影响

固体分散体可以有效解决难溶性药物口服生物利用度问题,但是固体分散体在储存过程中易发生相分离、重结晶等物理稳定性问题.制备工艺是影响固体分散体物理稳定性的重要因素之一.本文作者从固体分散体微观结构、宏观形态、药物与载体混合程度等角度出发,综述了制备工艺对固体分散体物理稳定性的影响机制,期望为固体分散体在药品研发中的应用提...     

依普黄酮固体分散体在大鼠的药物动力学评价

AIM: To evaluate pharmacokinetic behavior of ipriflavone solid dispersion in rats. METHODS: The plasma concentrations of ipriflavone in rats were determined by HPLC with UV detector. RESULTS: Plasma concentration-time curves after ig ipriflavone solid dispersion 250 mg.kg-1 in rats were fitted with one-compartment model. Pharmacokinetic parameters were as follows: Ke = 0.21 h-1, T1/2Ke = 5.19 h, Ka = 1.71 h-1, T1/2Ka = 0.41 h, Tmax = 0.67 h, Cmax = 429 micrograms.L-1, AUC = 3916 micrograms.h.L-1; The relative bioavailability of ipriflavone solid dispersion was 323%. CONCLUSION: Ipriflavone in solid dispersion was absorbed more effectively than that in physical mixture in rats.     

Astilbin attenuates hyperuricemia and ameliorates nephropathy in fructose-induced hyperuricemic rats

Astilbin is a flavonoid compound isolated from the rhizome of Smilax china L. The effects and possible mechanisms of astilbin on hyperuricemia and nephropathy rats were elucidated in this study. Different dosages of astilbin (1.25, 2.5, and 5.0 mg/kg) were administered to 10?% fructose-induced hyperuricemic rats. The results demonstrated that astilbin significantly decreased the serum uric acid (Sur) level by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) but not inhibiting the xanthine oxidase (XOD) activity. In addition, kidney function parameters such as serum creatinine (Scr) and blood urea nitrogen (BUN) were recovered in astilbin-treated hyperuricemic rats. Further investigation indicated that astilbin prevented the renal damage against the expression of transforming growth factor- β1 (TGF-β1) and connective tissue growth factor (CTGF) and also exerted a renal protective role by inhibiting formation of monosodium urate (MSU) and production of prostaglandin E? (PGE?) and interleukin-1 (IL-1). These findings provide potent evidence for astilbin as a safe and promising lead compound in the development of a disease-modifying drug to prevent hyperuricemia and nephropathy.     

冷冻干燥法制备甲苯磺酸拉帕替尼固体分散体及其大鼠药动学评价

目的用冷冻干燥技术制备甲苯磺酸拉帕替尼固体分散体,以提高其生物利用度。方法以PVPS630和soluplus^■为载体,采用冷冻干燥法制备甲苯磺酸拉帕替尼固体分散体,通过SEM、DSC、XRPD等手段对固体分散体进行表征,通过表观溶解度、溶出度和大鼠体内药动学测定,评价固体分散体的增溶效果和生物利用度的改善情况。结果在相同药载比的条件下,PVPS630组的溶出度和表观溶解度均优于soluplus^■组。DSC、XRPD、SEM等表征结果显示,PVPS630为载体的固体分散体中,原料均以非晶态存在,而以soluplus^■为载体时,只有药载比为1∶3条件下,原料才呈现非晶态特征。大鼠药动学测定结果表明,固体分散体(甲苯磺酸拉帕替尼-PVPS630为1∶3)较上市药品AUC提高23.64%。结论载体PVPS630与甲苯磺酸拉帕替尼的相容性更理想;固体分散技术有助于本品提高生物利用度。     

Role of glucose transporters in the intestinal absorption of gastrodin,a highly water-soluble drug with good oral bioavailability

Abstract

Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (T_max) was prolonged from 28 to 72?min when orally co-administered with four times higher dose of glucose. However, the T_max of gastrodin in diabetic rats was significantly lowered to 20?min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.     

A simple LC-MS/MS method for determination of magnolol in rat blood and its application in a pharmacokinetic study

A simple LC-MS/MS method was developed for determination and pharmacokinetic study of magnolol in rat blood. Blood sample pretreatment involved a one-step extraction with methanol of 100?μL blood. The chromatographic separation was carried out on a Agilent Zobax SB C18 column with a mobile phase consisting of acetonitrile-0.2% formic acid (55:45, v/v) at a flow rate of 0.3?mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via electro spray ionization source with positive mode. A high throughput was achieved with a run time of 4?min per sample. The standard curve for magnolol was linear (r > 0.999) over the concentration range of 2-1?000?ng/mL, with a lower limit of quantification of 2?ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 12% and the accuracy (relative error) was <5% at three quality control levels. This simple, fast and highly sensitive method was fully validated and successfully applied to a clinical pharmacokinetic study of magnolol in rats after oral administration.     

In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000

OBJECTIVE: Gliclazide is a potent antidiabetic agent because of its capability to decrease blood glucose level via stimulating endogenous insulin secretion from beta-pancreas cells. Gliclazide is insoluble in water and has low dissolution rate. In this study, polyethylene glycol (PEG) 6000 was used as a matrix to disperse gliclazide in the solid state, and the pharmacokinetic profile of this solid dispersion was studied in rats. DESIGN: The solid dispersion of Gliclazide:PEG 6000 (1:4) was prepared by solvent evaporation method. MAIN OUTCOME MEASURES: Samples characterization included differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and solubility and dissolution test. In vivo study was carried out in healthy rats, randomly. After a single dose of oral administration, blood samples were collected pre-dose (15 min before) and 1, 2, 3, 4, 5, 6, 8, 10, and 12 h post-dose. Plasma concentration of gliclazide was determined by high pressure liquid chromatography method using C-18 column, with mobile phase KH2PO4 (pH 4.6)-acetonitril (40:60 v/v) and UV detection at 229 nm. RESULTS: Results showed that there were no differences in DSC, IR spectroscopy, XRD, and dissolution test between the solid dispersion and physical mixture. In vivo data showed that the Tmax of gliclazide in solid dispersion and physical mixture was significantly decreased, while the Cmax, AUC(0-12), and AUC(0-infinity) were significantly increased compared to gliclazide alone. These results indicate that the rapid Tmax was due to rapid absorption of gliclazid across the GI tract membrane. Increased Cmax, AUC(0-12), and AUC(0-infinity) indicate a better absorption of gliclazide in solid dispersion and physical mixture than of gliclazide alone. CONCLUSION: Increased in gliclazide dissolution in the presence of PEG 6000 was followed by improved in vivo data.     

The exposure of luteolin is much lower than that of apigenin in oral administration of Flos Chrysanthemi extract to rats

Luteolin (3',4',5,7-tetrahydroxyflavone) and apigenin (4',5,7-trihydroxyflavone) are two common flavones and major bioactive components in Flos Chrysanthemi extract (FCE). Although FCE contains approximately equal amounts of luteolin (6.5%, w/w) and apigenin (5.4%, w/w), luteolin showed a much lower exposure than apigenin when FCE was orally administered to rats. The aim of the present study is to elucidate the mechanisms that caused the pharmacokinetic difference between luteolin and apigenin in rats. The results of an in situ rat intestinal single-pass perfusion model showed that the permeability of luteolin (k(a), 7.96×10?2 min?1 and P(eff), 4.87×10?3 cm/min) was about 50% that of apigenin (k(a), 18.5×10?2 min?1 and P(eff), 10.8×10?3 cm/min), which agreed with the observation that oral bioavailability of luteolin (30.4%) from FCE was significantly lower than that of apigenin (51.1%). On the other hand, luteolin was much more unstable than apigenin during the incubation with primary rat hepatocytes, and methylated metabolites of luteolin were detected after incubation. In addition, further metabolism of methylated luteolin also contributed to the faster elimination of luteolin. In conclusion, luteolin and apigenin are very similar in structure, however, one-hydroxyl difference gives them different characteristics in absorption and metabolism, which results in much lower exposure of luteolin than apigenin when FCE is orally administered to rats.     

LC-MS/MS法测定大鼠血浆中吴茱萸碱的浓度及其药代动力学研究

目的：建立用于测定吴茱萸碱血药浓度的液相色谱-串联质谱联用分析方法,并研究吴茱萸碱在大鼠体内的药代动力学。方法：6只大鼠灌胃给药吴茱萸碱100mg/kg,眼底取血,LC-MS/MS法测定血药浓度,并用DAS药代动力学程序拟合计算药代动力学参数。结果：吴茱萸碱浓度在0.2～50ng/mL内,线性关系良好（r^2=0.9997）。提取回收率96.12%～99.46%,日内、日间RSD分别为4.61%～13.51%和5.65%～11.49%。主要药代动力学参数为：Cmax=（5.3±1.5）ng/mL;tmax=（22±8）min;t1/2=（451±176）min。结论：建立的LC-MS/MS方法专属性强,灵敏度高,可用于吴茱萸碱的体内定量分析。     

LC-MS/MS法测定大鼠体内多西他赛血药浓度及其药动学研究

目的:建立测定大鼠血浆样品中多西他赛浓度的方法,并进行药动学研究。方法:以紫杉醇为内标,取8只大鼠尾静脉单剂量注射多西他赛5mg·kg-1,分别于给药前和给药后2、15、30、90、240、480、720、1440min眼眶后静脉丛采血,采用液相色谱-串联质谱法测定其血药浓度,并计算药动学参数。结果:多西他赛在大鼠体内的药-时曲线符合三室模型,主要药动学参数t12z为(236.44±53.47)min,c0为(3.84±0.97)mg·L-1,AUC(0～t)为(66.66±11.39)mg·min·L-1。结论:本方法专属性好、准确度好、灵敏度好,可为今后临床患者血药浓度监测和药动学研究提供方法学依据。     

毛冬青皂苷元ilexgenin A在大鼠体内的药动学研究

目的探讨静脉给予ilexgenin A后大鼠体内的药物动力学特征。方法采用HPLC测定大鼠血浆中的血药浓度,用DAS 2.0药动学软件求算其药动学参数。结果 Ilexgenin A在大鼠体内呈二室模型分布,主要药动学参数为:t1/2α=0.545min,t1/2β=18.338 min,Cl=0.019 L·min-1.kg-1,AUC0→t=2.5902 g·min·L-1。结论所用方法可用于大鼠血浆中ilexgeninA的检测及其体内药动学研究;静脉给药后,ilexgenin A在大鼠体内分布和消除迅速。