局部给药长效缓释的药代模型初探

目的创建局部给药长效缓释治疗系统的药代动力学模型。方法分析体内过程,建立微分方程并特别关注其中局部靶位的数学表达,进而对药物在血循环中及局部吸收位的分布作理论比较。结果缓释植入剂局部给药治疗系统的药代动力学二室模型为:Cc(t)=A1e-K rt A2e-Kat A3e-αt A4e-βt,吸收位与血循环中药物分布的比值为:ACc/ACa≈(Va/V)(Ka/Ke)。结论该模型立意严谨,有一定的理论意义和实用价值。     

牙周递药系统的研究进展

目的:了解牙周递药系统的研究进展。方法:根据文献,对牙周炎疾病的治疗药物的载药方式进行综述。结果与结论:牙周递药系统的载药方式包括脂质体、纤维剂、棒剂、膜剂、微球、缓释凝胶、黏固剂。牙周递药系统已由传统给药方式逐渐转为以高分子材料为载体的缓释制剂,具有局部给药剂量小、可持续稳定释放药物、使药物浓集于牙周袋内、提高药物疗效等特点,是很有发展潜力的药物传递系统。     

局部药代动力学的药物浓度时空方程初探

目的 建立局部植入给药的药物浓度时空方程。方法 将局部药物浓度时空方程构建为空间分布函数和时间分布函数(药物浓度经时方程)的积函数。并以加权平均及多元分析的数学手段予以证明及推导。结果 四维时空的局部植入给药的药物浓度时空方程的通式为：C(t，X，Y，Z)＝F(X，Y，Z)．C(t)，F(X，Y，Z)＝B0 B1X B2Y B3Z B4r3 B5r2 B6r,C(t)＝A1e^-Ket A2e^-Ket A3c^-Ket.。两维变量的简化的药物浓度时空方程为：C(t,ρ)＝F(ρ)．C(t)F(ρ)＝D0 D1ρ D2ρ2 D3ρ3，C(t)同上。结论 推导基本合理，并在初步的动物试验探索中得以验证。理论有较好科研价值，有助于揭示局部给药的药代动力学规律。     

纳米给药系统的药动学及毒理学研究进展

纳米给药是药剂学领域研究颇多的1种新型药物递送体系,具有超微体积及特殊结构,在控释、缓释、靶向给药以及黏膜、局部给药中,可提高难溶性药物与多肽药物的生物利用度,降低不良反应,在基因工程等领域中也显示出独特的优势。笔者综述了近年来报道的纳米给药系统在药动学、毒理学方面的研究,并简要介绍了纳米给药系统在药剂学领域中的研究进展。     

布洛芬巴布剂在兔体内的药动学

目的:研究布洛芬巴布剂在兔体内药动学。方法:用HPLC法测定兔分别给予布洛芬巴布剂和混悬液后不同时间点血浆中布洛芬的浓度,计算药动学参数和相对生物利用度,并对2种制剂的主要药动学参数分别进行单、双侧t检验。结果:布洛芬混悬液和自制巴布剂贴后的药动学过程均符合一房室一级吸收模型,2种制剂的主要药动学参数Ka、Ket、1/2(Ka)t、1/2(Ke)t、peak均有显著性差异(P<0.05),巴布剂具有缓释作用,当巴布剂给药量为口服液的2倍时可达到有效血药浓度,峰浓度与口服液的峰浓度差异无显著性,自制贴剂的相对生物利用度为(94.1±6.0)%。结论:与参比混悬剂相比,自主开发的巴布剂药动学参数发生了明显改变,且具有缓释作用。     

眼部给药系统的研究进展

随着现代社会人口老龄化、眼病患者的增多。眼用制剂的使用呈现高速增长趋势。由于眼部的生理结构特殊,药物在眼部的生物利用度偏低。为了使治疗药物进入眼内发挥疗效,新型眼用给药系统是近年来医药市场研究和开发的热点。未来的眼科用药需要新型的给药系统如凝胶系统、微球毫微粒给药系统、植入剂、插入剂、眼用冻干载体系统等,其优势是：提高了药物的吸收率,减少给药次数,降低药物的不良反应,在局部给药系统中具有独特性。现将新型眼用给药系统的特性、研究的进展及发展趋势作一论述。新型给药系统虽还有一些问题有待解决,但却是一个很有发展潜力的给药系统。     

眼部给药系统的研究进展

目的 介绍眼部给药系统的研究进展。方法 查阅总结近年来眼部给药系统的最新研究成果,展望其发展前景。结果 胶粒给药系统使不同阶段眼部疾病的治疗成为可能;靶向给药使得药物能够透过各种屏障到达眼部病变部位;原位凝胶显著延长了药物在眼部的滞留时间;可降解植入剂避免了释药后的二次手术;眼部电离子渗透技术大大降低了眼部治疗的创伤。结论 随着临床医学、药物制剂学、高分子材料学的发展及新技术的应用,眼部给药系统在眼部疾病治疗中的应用更加广泛,具有很好的发展前景。     

眼部给药系统的研究进展

目的介绍眼部给药系统的研究进展。方法查阅总结近年来眼部给药系统的最新研究成果,展望其发展前景。结果胶粒给药系统使不同阶段眼部疾病的治疗成为可能;靶向给药使得药物能够透过各种屏障到达眼部病变部位;原位凝胶显著延长了药物在眼部的滞留时间;可降解植入剂避免了释药后的二次手术;眼部电离子渗透技术大大降低了眼部治疗的创伤。结论随着临床医学、药物制剂学、高分子材料学的发展及新技术的应用,眼部给药系统在眼部疾病治疗中的应用更加广泛,具有很好的发展前景。     

双黄连注射液家兔直肠给药的药代动力学和相对生物利用度研究

目的 :研究双黄连注射液家兔直肠给药的药代动力学和相对生物利用度 ,对保留灌肠和口服给药进行比较 ,为直肠给药的科学性提供理论依据。方法 :将双黄连注射液中主药金银花的有效成分绿原酸作为血药浓度定量分析的检测指标 ,根据药物由用药部位进入体循环的速度 (即吸收速率Ka)和药物进入体循环的相对量 ,即吸收程度 ,通常用血药浓度时间 (CT)曲线下面积作指标 ,观察直肠给药的吸收动力学变化。结果 :药代动力学数据说明保留灌肠组与口服组间的AUC存在显著性差异 (P <0 .0 5 )。灌肠剂的生物利用度为 10 0 % ,口服剂的相对生物利用度则为 80 .78% ;保留灌肠剂和口服剂的达峰时间 (Tp 值 )分别是 0 .75和 2 .4 8h ,有显著的统计学意义 (P <0 .0 5 ) ,说明保留灌肠在吸收速度方面优于口服 ;Cmax受吸收量和吸收时间的影响 ,保留灌肠剂的血清浓度峰值与口服剂的峰值间存在显著性差异 (P <0 .0 5 ) ,说明保留灌肠剂的血药浓度明显高于口服剂。结论 :双黄连注射液有效成分的吸收 ,直肠比口服给药快 ,血药浓度高 ,其吸收总量和生物利用度均高于口服给药     

植入用缓释依托泊苷(VP-16)的药代模型—血浓方程初探

探讨并建立了植入用缓释依托泊苷的药代模型。结果显示 ,经 13例试验者数据拟合 ,其药代模型为 :单室 ,单剂量植入给药 ,血浓方程 C=A1 e- Ke t+ A2 e- Ka t+ A3e- Kr t。     

Efficient LRP1-Mediated Uptake and Low Cytotoxicity of Peptide L57 In Vitro Shows Its Promise as CNS Drug Delivery Vector

Although an abundance of drug candidates exists which are aimed at the remediation of central nervous system (CNS) disorders, the utility of some are severely limited by their inability to cross the blood brain barrier. Potential drug delivery systems such as the Angiopep family of peptides have shown modest potential; however, there is a need for novel drug delivery candidates that incorporate peptidomimetics to enhance the efficiency of transcytosis, specificity, and biocompatibility. Here, we report on the first in vitro cellular uptake and cytotoxicity study of a peptidomimetic, cationic peptide, L57. It binds to cluster 4 of the low-density lipoprotein receptor-related protein 1 (LRP1) receptor which is expressed in numerous cell types, such as brain endothelial cells. We used early-passage-number brain microvascular endothelial cells and astrocytes harvested from rat pup brains that highly express LRP1, to study the uptake of L57 versus Angiopep-7 (A7). Uptake of L57 and A7 showed a concentration-dependent increase, with L57 being taken up to a greater degree than A7 at the same concentration. Additionally, peptide uptake in LRP1-deficient PEA 10 cells had greatly reduced uptake. Furthermore, L57 demonstrated excellent cell viability versus A7, showing promise as a potential drug delivery vector for CNS therapeutics.     

高滴度特异性卵黄抗体在天花病毒检测中的研究

天花是人类第一个消灭的疾病,但生物界中仍广泛存在天花类病毒。目前人类还缺乏对其有效、快捷的诊断、检测和治疗措施。在全球面临生物恐怖袭击的时代,这方面的研究工作尤显迫切。以3种灭活的天花病毒（vaccinia virus,calpox virus和cowpox virus）为免疫原,分别免疫注射3组实验蛋鸡,以改良的聚乙二醇法将相应特异性抗体从卵黄中提取。利用免疫荧光实验、抗体中和实验及免疫电镜等实验持续检测抗体滴度变化以及抗体交叉反应。最后,以特异性的卵黄抗体与磁珠（Dynabead）相结合,用于天花病毒的纯化,并在PCR实验中验证其检测效果。抗vaccinia virus抗体和抗calpox virus抗体在高度稀释的情况下（分别以1：10^6,1：10^5稀释）,仍在免疫荧光实验中呈阳性反应,且抗体的这种高表达水平在持续5次免疫注射下,能维持达10个月。抗体的中和能力和抗体与抗原反应的超微结构也在相应实验中观察到。抗体与病毒蛋白结合的特殊条带也在免疫印记实验中观察到。实验显示,不同天花病毒之间存在强而明显的交叉反应。最后,特异性的卵黄抗体能够与磁珠结合,并在模拟样本中用于天花病毒的PCR检测。达到纯化病毒、增强PCR实验敏感度的效果。该研究显示,抗天花病毒卵黄抗体能够应用于天花病毒的诊断,有望以此为基础,开发出快速、有效的天花病毒检测手段。     

102例药物致中枢神经系统不良反应分析

目的了解引起中枢神经系统不良反应的药物及相关因素。方法收集两院上报的不良反应病例598例，筛选出中枢神经系统不良反应病例102例，用SPSS8．0进行分析。结果不良反应的发生与药物的剂量、给药途径、合并用药有关．老年人和儿童是易感人群。结论抗感染药物是引起中枢神经系统不良反应主要药物．其次是中枢神经系统药物。     

免疫新策略:经皮免疫

经皮免疫是一种将抗原和佐剂局部应用于皮肤诱导产生全身免疫反应的一种新方法。皮肤不但是组织外源性物质包括病原体进入体内的物理屏障,还是复杂有效的免疫系统,因此皮肤是重要的免疫接种靶标。在人类和多种动物的实验中,经皮免疫的效果已经得到了证实。经皮免疫是一种免疫的新策略,有着广阔的实际应用前景。     

Uptake of phenothiazines by the harvested chylomicrons ex vivo model: Influence of self-nanoemulsifying formulation design

The aim of this study was to examine the potential of self-nanoemulsifying drug delivery systems (SNEDDS) on the uptake of the lipophilic and poorly water soluble phenothiazines thioridazine and chlorpromazine with the isolated plasma derived chylomicron (CM) ex vivo model. The multi-component delivery systems were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation. The uptake of phenothiazines by isolated plasma derived chylomicrons was investigated with short chain triglyceride (SCT) SNEDDS, medium chain triglyceride (MCT) SNEDDS, and long chain triglyceride (LCT) SNEDDS. SNEDDS were also evaluated for their stabilities, dispersibilities, percentage transmittances and by particle size analyses. For thioridazine a 5.6-fold and for chlorpromazine a 3.7-fold higher CM uptake could be observed using a LCT-SNEDDS formulation compared to the drugs without formulation. In contrast, ex vivo uptake by isolated CM was not significantly increased by SNEDDS formulations based on MCT and SCT. Compared with isolated CM, the CM sizes were increased 2.5-fold in LCT-SNEDDS, whereas in MCT-SNEDDS or SCT-SNEDDS only a small, non-significant (P < 0.05) increase in CM size was observed. These results show that distinct SNEDDS formulations containing phenothiazines are efficiently uptaken by plasma derived chylomicrons ex vivo.     

The Effects of Clioquinol on P-glycoprotein Expression and Biometal Distribution in the Mouse Brain Microvasculature

Previous studies have demonstrated that the ionophore clioquinol (CQ), in conjunction with the biometals copper and zinc, increases the expression of P-glycoprotein (P-gp) in human cerebral microvascular endothelial (hCMEC/D3) cells. As P-gp expression and function at the blood-brain barrier (BBB) is of great interest regarding CNS drug access and endogenous toxin trafficking (e.g., amyloid beta), the present study assessed the in vivo translation of these previous in vitro findings. Swiss outbred mice received an 11-day treatment of CQ (30 mg/kg) by oral gavage, after which brain microvessel-enriched fractions (MEFs) and surrounding interfaces (subcortical brain tissue and plasma) were extracted. P-gp expression was quantified in the MEF, and biometal concentrations in all 3 compartments were assessed via inductively coupled plasma mass spectrometry. CQ treatment did not modify the expression of P-gp, nor copper or zinc concentrations in the brain MEF under this treatment regime. Metallomic analysis revealed, however, that CQ reduced potassium and magnesium levels in the brain MEF and also lowered brain iron levels. This study has shown that under this dosing regimen, CQ does not increase BBB P-gp expression in Swiss outbred mice, but that CQ facilitates redistribution of certain metal ions within the brain MEF, plasma, and brain parenchyma.     

In Vitro Simulation of Tissue Back-Pressure for Pen Injectors and Auto-Injectors

The aim of this project was to show that tissue back-pressure can be measured in vitro using a simple pneumatic model. A thorough literature study revealed 4 relevant papers all describing in vivo studies. One of these studies where the subcutaneous tissue back-pressure was determined in 11 patients was used as a reference for the present work. A pneumatic model capable of simulating the back-pressure and the diffusion of drug during subcutaneous injection was developed. The in vitro model was tested using the same type of pen injector as used in the reference study. Comparison of the results revealed that the measured pressure in the in vitro experiments was similar to the subcutaneous tissue back-pressure measured in vivo. G30 0.3 × 8.0 mm and G32 0.23/0.25 × 4.0 mm needles were used for the in vitro experiments, whereas a G31 0.25 × 6.0 mm needle was used for the in vivo experiments. This is one possible explanation of approximately 30 μL/s higher flow rates for the in vitro experiments compared to the in vivo experiments. The low-complexity model allows repeated measurements and provides a stable data output paving the way for measuring subcutaneous back-pressure in vitro.     

FIP Guidelines for Dissolution Testing of Solid Oral Products

Dissolution testing is an important physiochemical test for the development of solid oral dosage forms, tablets, and capsules. As a quality control test, the dissolution test is used for assessment of drug product quality and is specified for batch release and regulatory stability studies. In vitro dissolution test results can often be correlated with the biopharmaceutical behavior of a product.This article provides a summary of views from major global agencies (Europe, Japan, United States), pharmacopoeias, academia, and industry. Based on available guidance and literature, this article summarizes highlights for development and validation of a suitable dissolution method, setting appropriate specifications, in vitro–in vivo comparison, and how to obtain a biowaiver.     

Neglected disease - african sleeping sickness: recent synthetic and modeling advances

Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases relies on only six drugs, five of which have been developed more than 30 years ago, have undesirable toxic side effects and most of them show drug-resistance. Though development of new anti-trypanosomal drugs seems to be a priority area research in this area has lagged far behind. The given review mainly focus upon the recent synthetic and computer based approaches made by various research groups for the development of newer anti-trypanosomal analogues which may have improved efficacy and oral bioavailability than the present ones. The given paper also attempts to investigate the relationship between the various physiochemical parameters and anti-trypanosomal activity that may be helpful in development of potent anti-trypanosomal agents against sleeping sickness.