鬼臼毒素二棕榈酰磷胆碱脂质体治疗尖锐湿疣的临床研究

目的评价0.5%鬼臼毒素二棕榈酰磷脂酰胆碱(DPPC)脂质体治疗尖锐湿疣的临床效果和安全性。方法73例尖锐湿疣患者随机分为两组,治疗组(51例)用0.5%鬼臼毒素DPPC脂质体,对照组(58例)用0.5%鬼臼毒素酊剂。两组给药途径为外用,疗程7～21d。结果0.5%鬼臼毒素DPPC脂质体与0.5%鬼臼毒素酊剂治疗尖锐湿疣的治愈率分别为90.20%和91.38%,无显著性差异(P>0.05)。但治疗组不良反应和复发率明显低于对照组(P<0.05)。结论0.5%鬼臼毒素DPPC脂质体与0.5%鬼臼毒素酊剂具有相似的疗效,但其安全性高,复发率低。     

LC-MS/MS法测定尿二棕榈酰磷脂酰胆碱含量的方法学建立及其作为肾损伤标志物的研究(英文)

尿磷脂已被证实是非常灵敏的肾损伤标志物。然而,关于磷脂的研究大部分为定性或相对定量研究。因此,我们建立了定量测定尿中二棕榈酰磷脂酰胆碱(DPPC)的方法学来准确、特异地测定尿中DPPC含量。采用HILIC Silica(2.1 mm×50 mm,5μm)色谱柱,流动相为5 m M的甲酸铵–乙腈进行梯度洗脱,流速0.3 m L/min。该方法在2–200 ng/m L范围内线性良好,精密度、准确性、回收率、稳定性、稀释效应、基质效应等均符合FDA关于生物样本的检测要求。该方法应用于尿中DPPC的含量测定,并对DPPC作为肾损伤标志物的前景进行评价。     

新型阿霉素热敏脂质体的研制

目的:探讨以二棕榈酰磷脂酰胆碱(DPPC)和单棕榈酰磷脂酰胆碱(MPPC)为原料制备的温度敏感阿霉素脂质体的制备工艺和理化性质.方法:采用膜过滤挤压法和pH梯度法制备阿霉素脂质体,以紫外分光光度法检测样本中阿霉素含量,计算阿霉素热敏脂质体在不同温度下的药物释放特性,并对其包裹率、粒径,pH值进行研究.结果:阿霉素热敏脂质体在39℃下迅速释放,前20 s内释放药物50%,42℃下药物释放达到60%以上.包封率99.5%,平均粒径90.8 nm,pH值为6.5.结论:制备的热敏感阿霉素脂质体优于常规脂质体,具有良好的温度控释特性.     

高效液相色谱法测定多烯磷脂酰胆碱软胶囊中磷脂酰胆碱和溶血磷脂酰胆碱的含量

目的建立HPLC法测定多烯磷脂酰胆碱软胶囊中磷脂酰胆碱和溶血磷脂酰胆碱的含量以及有关物质方法。方法采用蒸发光散射检测器SEDEX55,MERCK的Li Chrospher 100 Diol-5色谱柱(125mm×4.0 mm,5μm);流动相A为正己烷-异丙醇-冰醋酸-三乙胺(814∶170∶15∶0.8),流动相B为异丙醇-超纯水-冰醋酸-三乙胺(844∶140∶15∶0.8),梯度洗脱。结果磷脂酰胆碱在0.912~2.736mg·mL~(-1),溶血磷脂酰胆碱在0.072~0.216 mg·mL~(-1)内与峰面积线性关系良好(R~2均为0.999)。磷脂酰胆碱的平均回收率为101.2%,RSD为1.3%;溶血磷脂酰胆碱的平均回收率为100.5%,RSD为1.9%。溶血磷脂酰胆碱的检测限为0.57μg。结论本检测方法专属性强,结果可靠,专属性强,重复性良好,可用于多烯磷脂酰胆碱软胶囊的质量评价。     

HPLC同时测定大豆磷脂中磷脂酰胆碱和溶血磷脂酰胆碱含量

目的建立同时测定大豆磷脂中磷脂酰胆碱（PC）和溶血磷脂酰胆碱（LPC）含量的方法。方法采用高效液相色谱法,色谱柱为Phenomenex silica柱（4.6 mm×150 mm,5μm）,流动相为正己烷-异丙醇-水（5∶80∶20）,流速：0.7 mL.min-1,检测波长：206 nm,柱温：25℃。结果 PC在0.4~2.4 mg.mL-1内呈良好的线性关系,平均回收率为99.4%,RSD为0.40%（n=6）;LPC在10~60μg.mL-1内呈良好的线性关系,平均回收率为98.0%,RSD为1.65%（n=6）。结论本试验方法简便、重复性好、专属性强,可作为大豆磷脂中PC,LPC的检测方法。     

N-（间马来酰亚胺苯甲酰）二棕榈酰磷脂酰乙醇胺的合成

间氨基苯甲酸与马来酸酐反应生成酰胺化合物,经脱水环合用N-羟基琥珀酰亚胺活化羧基,与二棕榈酰磷脂酰乙醇胺反应生成N-(间马来酰亚胺苯甲酰)二棕榈酰磷脂酰乙醇胺,总收率约29%.可用于制备主动靶向长循环脂质体.     

HPLC测定多烯磷脂酰胆碱胶囊中的溶血磷脂酰胆碱

目的 采用HPLC-ELSD测定多烯磷脂酰胆碱胶囊中溶血磷脂酰胆碱的含量.方法 色谱柱为硅胶(250 mm×4.6mm,5 μm),流动相A为正己烷-异丙醇(3:4),流动相B为正己烷-异丙醇-水(3:4:0.75),梯度洗脱,流速为1.5 mL·min~(-1),空气流速为3.0 L·min~(-1),蒸发管温度为100 ℃.结果 溶血磷脂酰胆碱0.1～1.5 mg·mL~(-1)与峰面积呈良好的线性关系(r=0.9997),平均回收率为99.90%.结论 所用方法简便、专属性好,可用于多烯磷脂酰胆碱胶囊中溶血磷脂酰胆碱的含量检测.     

丹参联合二亚油酰磷脂酰胆碱治疗病毒性肝炎疗效观察

1999年 4月至 2 0 0 0年 3月 ,我们采用丹参联合二亚油酰磷脂酰胆碱治疗病毒性肝炎 ,取得良好效果 ,现报告如下。材料和方法　本组 144例患者均系我科住院病人 ,诊断均符合 1995年全国传染病与寄生虫病学术会议 (北京 )修订的病毒性肝炎诊断标准。随机分为治疗组和对照组 ,治疗组 72例 ,男 50例 ,女2 2例 ,年龄为 ( 34± 8)岁 ;对照组 72例 ,男 4 7例 ,女 2 5例 ,年龄为 ( 33± 7)岁。治疗组急性病毒性肝炎 2 0例 ,慢性乙型肝炎 4 4例 ,亚急性重型肝炎 1例 ,慢性重型肝炎 5例 ,肝炎后活动性肝硬变 2例 ;对照组急性病毒性肝炎 2 3例 ,慢性乙…     

胰岛素与脂质体的相互作用

目的研究胰岛素与脂质体的相互作用。方法用荧光扫描、荧光淬灭、HPLC测定及微量量热方法,对胰岛素脂质体相互作用样品和超速离心、凝胶柱分离样品进行研究。结果胰岛素与脂质体相互作用后,胰岛素的荧光发射峰未发生蓝移,仅强度有所增加,荧光淬灭实验结果与胰岛素溶液基本相同,K_sv之比分别为0.9及0.81,微量量热实验表明为非共价键结合。分离后的样品经HPLC测定,胰岛素与脂质体的结合率只有0.2%,说明胰岛素与脂质体作用属弱吸附方式,未发生插膜(镶嵌);结合量小且强度低。结论胰岛素与脂质体相互作用的数量及程度均较弱,属于弱吸附的范畴。     

HPLC—ELSD测定注射用羟喜树碱脂质体中溶血磷脂酰胆碱的含量

目的建立了HPLC-ELSD法测定注射用控喜树碱脂质体中杂质溶血磷脂酰胆碱的含量,并初步研究了影响脂质体类制剂中磷妇水解的因素。方法用NH2柱（150×4．6mm,5μm）,以A：甲醇-氯仿（97：3）,B：2％草酸．乙醇（16：84）,A：B=7：3为流动相;柱温：30℃;流速为0．8mL·min^-1;进样量为20μL。结果注射用羟喜树碱脂质体中溶血磷脂酰胆碱能很好地分离检出。其线性浓度范围为：0．08～0．4mg·mL^-1（r=0．9991）;加样回收率为98．25％,rds=1．6％。结论该方法简便。准确、分析时间短,适用于注射用羟喜树碱脂质体中磷脂有关物质的测定。     

胰岛素脂质体的结构特点

目的研究胰岛素脂质体中胰岛素所处的位置及结构特点.方法采用激光散射测定其粒径大小与分布,用透射电镜测定形态;用HPLC法、荧光扫描、胰蛋白酶降解和聚丙烯胺凝胶电泳等实验手段研究胰岛素在脂质体中所处的位置.结果胰岛素脂质体平均粒径为218.3nm,多分散度为0.073,拟合度为7.2,形态多为圆球或近圆球形.HPLC测定结果显示,胰岛素脂质体中含有胰岛素;荧光扫描结果显示胰岛素脂质体中无胰岛素荧光发射峰;胰岛素脂质体可抵抗胰蛋白酶对胰岛素的降解;胰岛素脂质体的聚丙烯胺凝胶电泳谱图中未见胰岛素的条带.结论胰岛素脂质体中胰岛素被包裹在脂质体的内部,因此可抵抗胰蛋白酶的降解.     

氢化与非氢化卵磷脂对阿霉素脂质体体内外稳定性的影响

目的研究卵磷脂(EPC)和氢化卵磷脂(HEPC)对阿霉素脂质体的体外泄漏及体内循环时间的影响.方法用透析法考察EPC及HEPC普通脂质体在37℃小牛血清及37℃,20℃和4℃PBS中的药物泄漏情况;用高效液相色谱法研究了EPC和HEPC长循环脂质体在大鼠体内的药物动力学.结果在37℃小牛血清中HEPC脂质体较EPC脂质体泄漏慢,而在PBS中则结果相反;大鼠体内药物动力学研究结果表明,HEPC长循环脂质体在血中的平均驻留时间(MRT)较EPC长循环脂质体长得多(23.3h vs 12.0h).结论HEPC长循环脂质体是靶向血管外部位的更好的药物载体.     

BIOPHARMACEUTICAL EVALUATION OF THE LIPOSOMES PREPARED BY REHYDRATION OF FREEZE-DRIED EMPTY LIPOSOMES (FDELs) WITH AN AQUEOUS SOLUTION OF A DRUG

We have evaluated a method for preparation of a dispersion of liposomes encapsulating a drug, namely rehydration of freeze-dried empty (not containing drug) liposomes with an aqueous drug solution (FDEL method). In the present study, we characterized and compared this method with the conventional method using a lipid composition of DPPC–DPPG–cholesterol in a molar ratio of 27:3:20. Two hydrophilic compounds, [³H]-inulin and [³H]-mannitol, were used as model drugs. Liposomal preparations by the FDEL method had an encapsulation efficiency of 2.9 and 6.7% for [³H]-inulin and [³H]-mannitol, respectively, when rehydrated and incubated at 70 °C. Since non-specific adsorption of these markers to liposomal membrane is negligible, this method produces liposomes which encapsulate a drug in the intravesicular space. One-tenth of the marker encapsulated in the liposomes prepared by the FDEL method (F-liposomes) was released very rapidly on incubation with rat plasma, followed by the slow release of the remaining fraction thereafter. No such rapid-release phase was observed for the liposomes prepared by the conventional method (C-liposomes). This suggests the existence of two types of encapsulation, loose encapsulation and tight encapsulation, in F-liposomes at least. Pharmacokinetic parameters of marker encapsulated tightly in F-liposomes were comparable to those in C-liposomes. It is likely that amphipathic drugs such as doxorubicin are incorporated into liposomes more easily than inulin and mannitol when formulated by the FDEL method. These results therefore suggest that the FDEL method is useful in the preparation of a liposomal formulation of a drug.     

IN VIVO TRAFFICKING OF LONG-CIRCULATING LIPOSOMES IN TUMOUR-BEARING MICE DETERMINED BY POSITRON EMISSION TOMOGRAPHY

Various kinds of long-circulating liposome, such as ganglioside GM1-, polyethyleneglycol- (PEG-), and glucuronide-modified liposomes, have been developed for passive targeting of liposomal drugs to tumours. To evaluate the in vivo behaviour of such long-circulating liposomes, we investigated the liposomal trafficking, especially early trafficking just after injection of liposomes, by a non-invasive method using positron emission tomography (PET). Liposomes composed of dipalmitoylphosphatidylcholine, cholesterol, and modifier, namely, GM1, distearoylphosphatidylethanolamine (DSPE)–PEG or palmityl-D -glucuronide (PGlcUA), were labelled with [2-¹⁸F]-2-fluoro-2-deoxy-D -glucose ([2-¹⁸F]FDG), and administered to mice bearing Meth A sarcoma after having been sized to 100 nm. A PET scan was started immediately after injection of liposomes and continued for 120 min. PET images and time–activity curves indicated that PEG liposomes and PGlcUA liposomes were efficiently accumulated in tumour tissues time dependently from immediately after injection. In contrast, GM1 liposomes accumulated less in the tumour as was also the case for control liposomes that contained dipalmitoylphosphatidylglycerol (DPPG) instead of a modifier. Long-circulating liposomes including GM1 liposomes, however, remained in the blood circulation and avoided liver trapping compared with control DPPG liposomes. These data suggest that PGlcUA and PEG liposomes start to accumulate in the tumour just after injection, whereas GM1 liposomes may accumulate in the tumour after a longer period of circulation.     

紫杉醇隐形脂质体的制备及在小鼠体内的组织分布

目的　研究紫杉醇隐形脂质体的制备方法并考察其在小鼠体内的组织分布。方法　采用共沉淀和微流态化两步法制备紫杉醇隐形脂质体,用两亲性聚乙二醇-二硬脂酰磷脂酰乙醇胺(PEG-DSPE)修饰脂质体膜。以RP-HPLC法测定小鼠组织内紫杉醇药物浓度。结果　隐形脂质体粒径≤100 nm,药物包封率≥98%。均以5 mg.kg^-1经iv脂质体紫杉醇和游离紫杉醇,24 h后紫杉醇隐形脂质体在血液中驻留35%以上,在肝脾组织中摄取不足10%。而膜材中不含PEG-DSPE的紫杉醇传统脂质体在血液中驻留10%,被单核吞噬细胞系统(mononuclear phagocyte system, MPS)捕获了50%以上。证明紫杉醇隐形脂质体延长了在血循环中的时间并减少了MPS的吞噬。血液AUC隐形脂质体约为传统脂质体的2.0倍。结论　采用共沉淀和微流态化法可制得包封率高、粒径小的脂质体,用PEG-DSPE修饰磷脂膜可以增加隐形脂质体的AUC,并延长其在血循环中的时间。     

SERUM CONCENTRATIONS OF DIGOXIN ENTRAPPED IN LIPOSOMES AFTER INTRAVENOUS ADMINISTRATION IN DOGS

1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28–33 mol% in Hank's Buffer, pH 7.4 at 28°C. 2. Digoxin-liposomes (digoxin concentration 0.022 mg/kg per dog per day) administered intravenously in five adult male dogs attained therapeutic serum concentrations (0.7–3.0 ng/ml) beginning with day 1 of administration. 3. Digoxin serum concentrations obtained by intravenous digoxin-liposomes compared favorably with normal oral digoxin administration (0.022 mg/kg per dog per day) in all 5 dogs monitoring serum digoxin levels for 7 days showed no significant (P<0.05) differences in mean serum digoxin concentrations ± s.e.m. on 6 of 7 days of treatments.     

胰岛素滴眼液实验研究进展

综述了胰岛素滴眼液实验研究的近期进展。胰岛素滴眼液中如加入吸收促进剂ＢＬ－９或Ｂｒｉｊ－７８，药物经眼结膜和鼻泪管粘膜吸收可产生明显的降血糖作用，且长期应用对眼无明显毒性，未见过敏反应和药物耐受性，有临床应用价值。     

THE EFFECTS OF KININS AND THEIR INTERACTIONS WITH ADRENERGIC MECHANISMS ON THE BEHAVIOURAL ACTIVITY OF RATS

SUMMARY 1. Intraperitoneal administration of kallikrein (50 u/kg) to rats increased the kinin-forming activity of the brain but had no effect on behaviour.
2. Injection of bradykinin (1 μg) into a cerebral ventricle slightly decreased the behavioural activity of rats.
3. The increase in activity produced by pretreatment with nialamide (200 mg/kg) was greatly potentiated by administration of kallikrein or bradykinin in the doses and by the routes mentioned above.
4. Injection of noradrenaline (50 μg) into a cerebral ventricle had no effect on activity in normal rats and slightly increased the activity of rats pretreated with reserpine.
5. When noradrenaline was given with kallikrein or bradykinin, activity was markedly increased in normal and reserpinized rats.
6. The results suggest that kinins may influence central neurotransmission.     

柔红霉素长循环脂质体的药剂学性质及大鼠体内药代动力学研究

目的研究柔红霉素长循环脂质体的药剂学性质及大鼠体内药代动力学。方法考察柔红霉素长循环脂质体的形态和粒径分布、包封率和加速实验稳定性;建立脂质体中柔红霉素含量测定的可见分光光度法和HPLC方法;考察脂质体在Hepes缓冲液(pH 7.5)和大鼠血清中的体外释放行为。考察脂质体在大鼠体内的药代动力学行为。结果制备的柔红霉素长循环脂质体包封率高(>85%)、稳定性好,平均粒径为56.3 nm,体外释放慢;长循环脂质体的T_1/2α和AUC分别是注射剂的17.6和96倍。结论制备的长循环脂质体包封率较高,药剂学性质稳定,在大鼠体内的药代动力学参数优于注射剂,能达到长循环目的。