紫杉醇给药研究进展

紫衫醇是具有良好抗癌活性的天然药物。但由于极差的水溶性，大大地限制了它在临床上的应用。为此开发适宜的紫衫醇给药系统成为紫杉醇大规模应用的关键。本文综述了紫衫醇给药的最新进展，归纳了几种给药的途径，为紫杉醇给药系统的研究提供了一些线索。     

紫杉醇聚合物胶束载药体系的研究进展

紫杉醇（paclitaxel,PTX）是一种常用的抗肿瘤药物,但其极差的水溶性限制了其在临床上的应用。为使其能更好的为人体所利用,近年来,研究者们开发了多种紫杉醇载药体系,其中聚合物胶束载药体系以其特有的优点为目前研究的热点,并具有广阔的发展前景。介绍了近年来采用两亲嵌段共聚物制备紫杉醇聚合物给药体系的研究进展。展望了该体系今后的发展方向。     

药物纤维及其在新型给药系统中的应用

综述了制备药物纤维的材料和技术以及药物纤维在新型给药系统(DDS)中的应用。分析了目前药物纤维DDS技术存在的问题。药物纤维可分为原料型、天然纤维的后整理型、聚合物型及复合型。其制备方法主要有传统纺丝方法、静电纺丝技术、非织造布技术以及后整理技术。指出中草药纤维的DDS、智能释药纤维DDS及多药多级控释DDS是今后药物纤维DDS研究的方向。     

紫杉醇-SIBS体外药物释放动力学研究

采用聚（苯乙烯-b-异丁烯-b－苯乙烯）三嵌段共聚物（SIPS）作为紫杉醇药物载体,研究了紫杉醇释放动力学行为。对紫杉醇-SILKS载药共聚物进行了差示量热扫描仪分析（DSC）和原子力显微镜（AFM）的表征;研究了不同苯乙烯（St）含量的紫杉醇-SIBS载药共聚物在pH=7．4磷酸缓冲液（PBS）（37℃）中的动力学。结果表明紫杉醇-SIRS载药共聚物随着St含量的增加,紫杉醇的释放率较低,且其释药率在8d以后趋于平稳;在体外释药过程中随着磷酸缓冲液的置换量越大,紫杉醇的释放率越高。     

外加紫杉醇后南方红豆杉细胞的耐受性及其凋亡的研究

利用显微照相和DNA提取等技术，研究了外源紫杉醇作用于服浮培养南方红豆杉细胞（Taxus chinensis var.Mairei)的凋亡和对紫杉醇（taxol）的耐受性。利用荧光显微照相技术观察到，外源紫杉醇作用下，随培养时间延长，南方红豆杉细胞发生明显核分化，应用DNA电泳观察到细胞DNA断裂形成典型的180bp及其整数倍梯形条带（DNA.ladders) ,应用TUNEL检测发现DNA的3'-OH断端可被特异性标记，证实了加入紫杉醇后南方红豆杉细胞发生了凋亡。研究结果说明南方红豆杉细胞对紫杉醇的耐受性是有限度。并证明了植物细胞有类似于动物细胞的凋亡特征，也表明该体系可以作为研究植物细胞凋亡的实验模型。     

小分子药聚乙二醇化的利与弊

聚乙二醇（PEG）是一种水溶性、无毒、无免疫原性的两性化合物，可被机体安全清除．1977年的文献中出现了基于PEG单元重复的技术，称为PEG化．大分子药物（包括稳定的分子和前药）经PEG化后可获得重要的药动学性质，带来许多临床利益，包括提高疗效、降低副作用和给药频率．大分子药物的PEG化技术适用于多种药物，如抗肿瘤、     

紫杉醇-油酸和鸦胆子油纳米乳抑制Hela细胞的研究

目的研究紫杉醇-油酸和鸦胆子油纳米给药系统(PTX-OA/BJO CMNEs)抗宫颈癌细胞(Hela)的机制与效应。方法通过流式细胞仪检测BJO CMNEs、PTX-OA/BJO CMNEs、PTX-OA CMNEs、Blank CMNEs对Hela细胞细胞周期和细胞凋亡的影响。采用噻唑蓝比色法测定细胞毒作用。结果 MTT结果显示,在一定浓度范围内,PTX-OA/BJO CMNEs组与PTX-OA CMNEs组抑制率存在显著差异(P0.01)。周期结果显示,PTX-OA/BJO CMNEs组(40.48±0.58%)停滞在S期的细胞与PTX-OA CMNEs组(35.23±0.34%)具有统计学意义(P0.05)。凋亡结果显示,PTX-OA/BJO CMNEs组凋亡率为30.50±2.55%,PTX-OA CMNEs是19.80±1.27%,两组差异有统计学意义(P0.01)。结论本研究表明紫杉醇和鸦胆子油两药联用的细胞毒性,细胞周期阻滞和细胞凋亡诱导作用均优于单独用药,具有增强作用。联合用药的抗肿瘤细胞作用机制包括诱导细胞凋亡,阻滞细胞周期,抑制细胞DNA复制和细胞增殖活性等途径。     

紫杉醇提取分离及其资源的研究进展

1前言紫杉醇（taxol）是从红豆杉属（Taxus）植物中分离到的一个种具有独特抗肿瘤活性的二储类化合物,1992年底被美国FDA正式批准为抗卵巢癌的新药。虽然紫杉醇的全合成已获成功,但就目前临床供药而言,主要还是依靠从植物中提取。无论是从天然的红豆杉植物还是从培养的植物细胞组织中提取紫杉醇,都要涉及到如何能分离并去掉与紫杉醇结构相似的其它紫杉烷类化合物。由于这些紫杉烷类化合物在化学结构和极性等方面都同紫杉醇极为相似,因此给分离工作带来很大的困难。如何更好地分离紫杉酸及其类似物质,无论在基础研究还是在实用价值上…     

五味子酯乙对肺癌耐紫杉醇A549/Tax细胞的多药耐药逆转作用及机制

目的:研究探讨五味子酯乙对肺癌耐紫杉醇A549/Tax细胞的肿瘤多药耐药(MDR)逆转作用及机制。方法:MTT法检测分析五味子酯乙单独或联用阿霉素、紫杉醇对耐药A549/Tax细胞及其亲本敏感A549细胞的细胞毒性及MDR逆转作用,阿霉素蓄积实验和Pgp-GloTMAssay Systems分析检测五味子酯乙对P糖蛋白(P-gp)外排功能及P-gp ATPase活性的影响,Westen blot检测分析A549/Tax细胞中P-gp和β-actin的蛋白水平。结果:五味子酯乙(1.0、2.5、5.0μmol/L)剂量依赖性提高紫杉醇和阿霉素对P-gp过表达的A549/Tax细胞的抗增殖活性,激活P-gp ATPase活性并底物竞争性的抑制P-gp的药物外排转运功能,下调P-gp的过表达。结论:五味子酯乙通过底物竞争性抑制P-gp的药物外排功能和下调其蛋白水平有望在临床中克服P-gp过表达介导的MDR。     

国内信息

国内信息●紫杉醇提取分离方法的研究进展乙酸乙酯－丙酮（１∶１）可试用于紫杉醇的提取，氧化铝柱可用于提取水溶性的糖基紫杉醇：用含２０％～５０％的Ｈ２Ｏ的乙醇溶液结合活性炭吸附法有利于枝叶中紫杉醇的提取与分离；利用超临界流体进行大量原料萃取尚无现实可能性...     

红豆杉细胞两液相耦合培养过程中细胞凋亡与紫杉醇含量的关系

以油酸作为有机相与改良B5液体培养基组成耦合培养体系 ,研究了在该体系中悬浮培养的红豆杉细胞凋亡与紫杉醇含量的关系 .结果表明 ,紫杉醇的总含量随凋亡率呈抛物线规律变化 ;耦合培养法有效地促进了胞内紫杉醇向胞外释放 ,绝大部分储存于有机相中 ,从而降低了紫杉醇影响细胞凋亡发生的可能性 ,因此推测是细胞凋亡促进了紫杉醇的大量合成     

南方红豆杉细胞两液相培养过程动力学

建立了摇瓶中南方红豆杉细胞两液相培养过程动力学模型 ,提出的有机溶剂毒性参数 1 0 /lgP使建立的模型不仅能确切反映两液相培养细胞生长和紫杉醇生产随时间、不同的有机溶剂 (烷烃、有机酸、醇和酯 )和有机溶剂体积分数等的变化规律 ,而且将有机溶剂毒性参数 1 0 /lgP取为 1、有机溶剂体积分数取为 0时模型可确切反映单液相培养细胞生长和紫杉醇生产的变化规律 .根据模型求解和结果分析 ,深入研究了这些变化规律的机理 .     

Curing,compatibility, and fracture toughness for blends of bismaleimide and a tetrafunctional epoxy resin

The curing, compatibility, and fracture toughness of blends of 4,4 ′-bismaleimidodiphenylmethane (BDM)/tetraglycidyl diamino-diphenyl methane (TGDDM) were investigated. Diamino-diphenyl sulfone (DDS) was used as a curing agent. BDM alone could be both homopolymerized (at a lower temperature) and could also undergo Michael addition reactions with the primary amine of DDS. The secondary amine of DDS did not react with BDM. However, the network produced by homopolymerization was not miscible with that produced by the latter reactions. Curing of TGDDM with DDS took place almost at the same temperature as that of the homopolymerization of BDM, but well below the temperature of the Michael addition reaction. When a BDM/TGDDM mixture was cured with DDS in the stoichiometric ratio, the miscibility of the cured system increased with the amount of TGDDM. This was attributed to the fact that the network produced by Michael addition reactions was diminished. When DDS reacted entirely with TGDDM, the BDM/TGDDM/DDS cure yielded only a TGDDM/DDS network and a BDM homopolymerized network, which were not only miscible, but are also interpenetrating. The superior interpenetrated network, as indicated by the highest fracture toughness, was found at BDM/TGDDM = 40/60 weight ratio in the BDM/TGDDM/DDS curing systems.     

含紫杉醇PLGA缓释微球的研制及理化性质

目的研制含紫杉醇的聚乳酸和乙醇酸的共聚物[Poly(lactic-co-glycolic acid),PLGA]生物可降解高分子微球,并对其药物释放动力学进行分析。方法使用相对分子质量为20000的PLGA作为造粒对象,对不同溶剂的PLGA溶液进行喷雾化造粒,以优化出最佳造粒参数。在此条件下对含紫杉醇的PLGA溶液进行喷雾化造粒,制备紫杉醇/PLGA微球。结果形成单分散粒子的条件是较高的应用电压和较低的溶液流率,5%(wt)的PLGA溶液浓度溶于5∶1的氯仿和DMF的混合溶剂(v/v)中。在优化的喷雾参数下,得到了粒径均一、直径为300nm的单分散载紫杉醇的PLGA微粒。当紫杉醇在微球中含量较低时(2%),药物释放呈零级释放模式。较高的载药浓度(>5%)会在初期有轻微药物突释,然后呈零级释放模式。结论电喷雾化技术制备载药微粒是简单可行的新制药技术。含紫杉醇的PLGA微粒有望成为新一代抗癌药物剂型。     

C18-硅胶的原位合成及其作为常压层析介质在紫杉醇分离纯化中的应用

以氯铂酸为催化剂,采用原位法合成了造价低廉、性能稳定的Ｃ１８－反相层析介质。考察了原位法第二步反应中催化剂、反应时间及反应温度等对介质合成的影响。将合成的Ｃ１８－硅胶应用于紫杉醇的常压层析提纯,可使紫杉醇的纯度从２７％提高到９５％以上,回收率大于９０％。     

Effects of cyclooxygenase inhibitors in combination with taxol on expression of cyclin d1 and ki-67 in a xenograft model of ovarian carcinoma

The present study was designed to investigate the effects of cyclooxygenase (COX) inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor) alone, 3 mg/kg SC-560 (a COX-1 selective inhibitor) alone by gavage twice a day, 20 mg/kg taxol alone by intraperitoneally (i.p.) once a week, or celecoxib/taxol, SC-560/celecoxib, SC-560/taxol or SC-560/celecoxib/taxol, for three weeks. To test the mechanism of the combination treatment, the index of cell proliferation and expression of cyclin D1 in tumor tissues were determined by immunohistochemistry. The mean tumor volume in the treated groups was significantly lower than control (p < 0.05), and in the three-drug combination group, tumor volume was reduced by 58.27% (p < 0.01); downregulated cell proliferation and cyclin D1 expression were statistically significant compared with those of the control group (both p < 0.01). This study suggests that the effects of COX selective inhibitors on the growth of tumors and decreased cell proliferation in a SKOV-3 cells mouse xenograft model were similar to taxol. The three-drug combination showing a better decreasing tendency in growth-inhibitory effect during the experiment may have been caused by suppressing cyclin D1 expression.     

Microstructure and properties of new polyimide/polysiloxane composite films

A series of novel polyimide/polydiphenylsiloxane) (PI/PDDS) composite films with different contents of DDS were prepared using sol–gel method. The noncrosslinked PI–DDS and crosslinked PIS–DDS were synthesized through cohydrolysis and condensation between DDS and polyamic acid (PAA) or aminopropyltriethoxysilane(APTES)‐terminated polyamic acid (PAAS). All the composite films have high thermal stability near pure PI. Field emission scanning electron microscopy (FE‐SEM) study shows that the polysiloxane from hydrolyzed DDS well dispersed in polyimide matrix, without macroscopic separation for the composite films with low content of DDS, while large domain of polysiloxane was formed in films with high DDS content. The microstructure of composite films is in accordance with the transparency of corresponding films. X‐ray study shows the PDDS is amorphous in PI matrix. The introduction of DDS into PI can improve the elongation at break and at the same time, the composite films still remained with higher modulus and tensile strength. The density and water absorption of the composite films decreased with the increasing DDS content. The composite films with DDS content below 10 wt % exhibit good solvent resistance. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 124–132, 2006     

Novel adamantane‐containing epoxy resin

A novel adamantane‐containing epoxy resin diglycidyl ether of bisphenol‐adamantane (DGEBAda) was successfully synthesized from 1,3‐bis(4‐hydroxyphenyl)adamantane by a one‐step method. The proposed structure of the epoxy resin was confirmed with Fourier transform infrared, ¹H‐NMR, gel permeation chromatography, and epoxy equivalent weight titration. The synthesized adamantane‐containing epoxy resin was cured with 4,4′‐diaminodiphenyl sulfone (DDS) and dicyandiamide (DICY). The thermal properties of the DDS‐cured epoxy were investigated with differential scanning calorimetry and thermogravimetric analysis (TGA). The dielectric properties of the DICY‐cured epoxy were determined from its dielectric spectrum. The obtained results were compared with those of commercially available diglycidyl ether of bisphenol A (DGEBA), a tetramethyl biphenol (TMBP)/epoxy system, and some other associated epoxy resins. According to the measured values, the glass‐transition temperature of the DGEBAda/DDS system (223°C) was higher than that of the DGEBA/DDS system and close to that of the TMBP/DDS system. TGA results showed that the DGEBAda/DDS system had a higher char yield (25.02%) and integral procedure decomposition temperature (850.7°C); however, the 5 wt % degradation temperature was lower than that of DDS‐cured DGEBA and TMBP. Moreover, DGEBAda/DDS had reduced moisture absorption and lower dielectric properties. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Controlled release of berberine hydrochloride from alginate microspheres embedded within carboxymethyl chitosan hydrogels

Berberine hydrochloride is a natural medicine with wide clinical application. In this article, berberine hydrochloride was entrapped into alginate microspheres via an emulsification/gelation method. The size distribution of the microspheres was determined by a laser particle sizer. Drug distribution within the microspheres was determined by confocal laser scanning microscopy. Those drug‐loaded microspheres were further entrapped into carboxymethyl chitosan (CMC) hydrogel to form a new drug‐delivery system (DDS). The surface morphology of the DDS was observed using metallographic microscopy and scanning electron microscopy (SEM). The compression strength of the DDSs with alginate microspheres was found significantly higher than that of the pure hydrogel. The drug‐release performances of the DDS in phosphate buffer solution (PBS, pH 7.4), saline solution (pH 6.3), and hydrochloric acid solution (HAS, pH 1.2) were also studied. Decay of the DDS in PBS within 72–80 h results in a faster release; however, the steady release in saline solution could last for all the testing period without cleavage of the DDS. In HAS, because of the shrinkage of the DDS, release is fast in the first period and remains steady later. The DDS exhibits prospective in controlled steady release of drugs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

二苯基二甲氧基硅烷稳定性研究

以自然放置法和线性变温法研究了二苯基二甲氧基硅烷的稳定性 ,二者结论一致。其反应活化能 :138 15 15kJ/mol,2 5℃反应速度常数为 1 0 6 73× 10 -4/d。建立了反应速度常数K与温度T间关系的方程。可准确计算其有效期 ,正确预测贮存后其真实浓度。并分析了其分解反应类型