平阳霉素及其微球制剂的研究进展

平阳霉素自发现以来一直作为抗肿瘤的一线用药得到人们的广泛关注。近年来,将平阳霉素制备成微球剂型,改变其体内代谢过程,延长药物的作用时间,增强平阳霉素的疗效成为医药学界的研究热点。本文首先通过平阳霉素与博来霉素的对比体现出平阳霉素的优势;之后对平阳霉素的临床应用、不良反应等方面进行了相关介绍,经总结得出平阳霉素具备高效低毒的特点;最后对平阳霉素微球研究的最新进展进行了概括,并提出了该药物在未来应用方面的展望。     

沉淀聚合法制备1-脱氧野尻霉素分子印迹聚合物微球及其性能研究

本研究制备了1-脱氧野尻霉素分子印迹聚合物微球,考察溶剂、反应时间对分子印迹聚合物产率以及性能的影响。以1-脱氧野尻霉素为模板分子,α-甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(EGDMA)为交联剂,采用沉淀聚合法合成分子印迹微球,采用静态吸附及扫描电镜(SEM)的方法对微球进行表征。结果表明,当反应时间为24 h、乙腈为溶剂时,所制得印迹聚合物微球的形貌和吸附性能较好,对1-脱氧野尻霉素与N-甲基-1-脱氧野尻霉素的选择性分离因子α为2.26,说明分子印迹聚合物微球对1-脱氧野尻霉素分子有特异性吸附和识别能力。     

盐酸平阳霉素有关物质检查方法的对比研究

目的:寻找更加适合我国盐酸平阳霉素的同族杂质组分的检查方法。方法:通过对我国药典盐酸平阳霉素中有关物质检查法与日本药局方中硫酸博莱霉素有关物质检查法进行对比研究。结果:中国药典中的高效液相色谱(HPLC)法测定盐酸平阳霉素有关杂质优于日本药典方法。结论:我国药典有关物质检查法更加适合盐酸平阳霉素的同族杂质组分的检查。     

术前应用平阳霉素化疗配合改良手术治疗 阴茎癌疗效的初步观察

目的：探讨应用平阳霉素化疗配合改良手术治疗阴茎癌的治疗效果。方法：104例阴茎癌患者,平均年龄55．3岁,手术前皆进行病例组织活检证实,术前应用平阳霉素化疗7。14天,并在化疗后行阴茎部分切除术＋改良方法的腹股沟淋巴结清扫术。,观察术后情况,并进行跟踪随访。结果：所有患者化疗反应轻微,化疗后肿瘤明显缩小者26．9％,肿瘤脱落者6．9％。无变化者23．7％。术后皮瓣严重坏死者14．4％;轻度坏死者13．5％;无坏死者72．1％。出现下肢水肿者24．0％。随访4～10年,正常存活46．6％;出现远处转移者18．3％;死亡17．1％。结论：术前应用平阳霉素化疗可使部分阴茎癌组织明显缩小,甚至瘤体脱落,手术可最大范围地保留阴茎功能。改良腹股沟淋巴结清扫术缩小了清扫范围,减轻了下肢及阴囊水肿,提高了患者的生活质量和生存率。     

MS-275联合平阳霉素对Tca-8113细胞生长和凋亡的影响

目的:观察组蛋白去乙酰化酶抑制剂(HDACIs)MS-275联合抗生素类化疗药物平阳霉素(PYM)对口腔鳞状癌细胞Tca-8113的生长及凋亡的影响。方法:以体外培养的口腔鳞状细胞癌Tca-8113细胞为研究对象,应用MTT法检测不同浓度(0、1、2、4、8μmol/L)MS-275、(0、0.05、0.1、0.2、0.4μmol/L)平阳霉素(PYM)单独和联合用药对Tca-8113细胞增殖活性的影响;Annexin-V-FITC/PI双染流式细胞术定量检测细胞的凋亡情况。结果:不同浓度(1、2、4、8μmol/L)MS-275和(0.05、0.1、0.2、0.4μmol/L)PYM均可显著抑制Tca-8113细胞的增殖,并促进其凋亡,且呈浓度依赖性(P0.05)。4μmol/L MS-275和0.2μmol/L PYM联合应用时,其抑制Tca-8113细胞增殖和促进其凋亡的作用均显著高于单独应用MS-275或PYM(P0.05)。结论:MS-275能有效增强口腔鳞状细胞癌Tca-8113细胞对平阳霉素(PYM)的敏感性,体外实验中呈现较好的抗肿瘤效应。     

海藻酸钠壳聚糖微球作为药物载体的研究进展

海藻酸钠壳聚糖微球是具有生物粘附性且能结合和传递大分子药物的天然高分子材料,且在生物医学领域具有广阔应用前景的药物载体。它具有生物黏附性、生物相容性、生物可降解性、对人体无毒性且能够结合和传递大分子药物的天然高分子材料。海藻酸钠壳聚糖微球作为载药微球具有提高药物的生物利用度、延长药物的作用时间等优点。国内外近些年已将其应用于药剂学领域,以及将其作为药物载体经微球化与药物结合形成给药系统的研究也在逐步开展并取得了较多成果。本文主要阐述海藻酸钠壳聚糖微球的主要生物特性、作用特点及其在医学领域中应用的研究进展,并对其应用前景进行探讨。     

白细胞介素2联合平阳霉素治疗恶性胸水52例的疗效观察

介绍了白细胞介素 2加平阳霉素联合治疗恶性胸水的疗效。联合用药组 5 2例恶性胸水患者中 ,完全缓解2 6例 ,占 5 1.0 % ;部分缓解 18例 ,占 34 .6 % ,其总有效率为 84.6 % ,高于 2 8例用平阳霉素单药化疗组的有效率6 4.3%。同时 ,患者生存质量也高于单药化疗组 ,有显著差异 (P <0 .0 5 )。两组副作用相差不大     

纳米微球药物缓释技术

纳米微球作为药物载体被越来越多地应用于医药领域,这一技术得到研究者的广泛重视。目前已有多种纳米微球制剂投入临床使用。纳米微球的深入研究具有重要的意义。我们概述了近年来纳米微球的研究及应用情况,展望了纳米微球药物载体缓释技术的应用前景及需要解决的问题。     

抗细菌药物默诺霉素的化学生物学研究进展

默诺霉素(moenomycins)家族类化合物主要是由链霉菌产生,属于磷酸糖脂类抗生素。该类化合物通过与细菌细胞壁肽聚糖糖基转移酶(peptidoglycan transferase,PGT)的活性位点结合,可以抑制众多革兰氏阳性细菌细胞壁的合成,具有很强的生物活性和重要的应用开发潜力。本文针对默诺霉素的化学结构、生物活性机制、抗性机制、生物合成研究途径、外排机制和新结构创制等化学生物学方面进行了系统综述,并对默诺霉素化学生物学研究现状以及可能存在的问题进行了总结,旨在为高活性磷酸糖脂类临床药物的研究与开发提供借鉴。     

井冈霉素研究概况(综述)

对井冈霉素的生产、应用、检测技术和作用机理等方面的研究进展进行综述,并就未来井冈霉素的研究方向提出建议。     

Pingyangmycin inhibits glycosaminoglycan sulphation in both cancer cells and tumour tissues

Pingyangmycin is a clinically used anticancer drug and induces lung fibrosis in certain cancer patients. We previously reported that the negatively charged cell surface glycosaminoglycans are involved in the cellular uptake of the positively charged pingyangmycin. However, it is unknown if pingyangmycin affects glycosaminoglycan structures. Seven cell lines and a Lewis lung carcinoma-injected C57BL/6 mouse model were used to understand the cytotoxicity of pingyangmycin and its effect on glycosaminoglycan biosynthesis. Stable isotope labelling coupled with LC/MS method was used to quantify glycosaminoglycan disaccharide compositions from pingyangmycin-treated and untreated cell and tumour samples. Pingyangmycin reduced both chondroitin sulphate and heparan sulphate sulphation in cancer cells and in tumours. The effect was persistent at different pingyangmycin concentrations and at different exposure times. Moreover, the cytotoxicity of pingyangmycin was decreased in the presence of soluble glycosaminoglycans, in the glycosaminoglycan-deficient cell line CHO745, and in the presence of chlorate. A flow cytometry-based cell surface FGF/FGFR/glycosaminoglycan binding assay also showed that pingyangmycin changed cell surface glycosaminoglycan structures. Changes in the structures of glycosaminoglycans may be related to fibrosis induced by pingyangmycin in certain cancer patients.     

新制癌菌素和平阳霉素诱发蚕豆染色体畸变的比较研究

本文报道了新制癌菌素(NCS)能诱发植物染色体畸变,同时观察了利用咖啡因后处理对NCS、PYM诱发染色体畸变的影响,研究了PYM切断DNA断头的性质。结果表明,NCS切割DNA产生3'-羟基末端和3'-磷酸末端;咖啡因能封闭3'-羟基末端抑制DNA的修复,从而提高诱变频率。PYM加咖啡因后处理,其染色体畸变频率与PYM单独处理无明显差异。说明PYM切断DNA所得到的产物,不是3'-羟基末端,而是3'-磷酸末端。     

白内障晶体中某些微量元素、与谷胱甘肽相关酶类活性的动态观察及其相互关系

本文动态观察了用平阳霉素诱发的大鼠白内障晶体中与谷胱甘肽代谢相关酶类活性和微量元素水平的变化,并与正常晶体进行比较,同时就酶活性与微量元素水平的相关性进行了检验。结果表明：（１）注射平阳霉素早期酶活性增高,谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）、谷胱甘肽还原酶（ＧＳＳＧ－Ｒ）及超氧化物歧化酶（ＳＯＤ）等活性的升高达显著水平,后期酶活性均下降,尤以ＧＳＨ－Ｐｘ、ＧＳＳＧ－Ｒ和谷胱甘肽硫转移酶（ＧＳＨ－Ｓ）等的活性降低明显;（２）ＧＳＨ－Ｐｘ和ＳＯＤ酶活性分别与Ｚｎ具有相关性（Ｐ＜０．０５）,这两种酶也分别与Ｓｅ具有高度相关性（Ｐ＜０．０１）,此两种元素在该类型白内障形成中可能有一定意义。     

生长因子PLGA微包囊成形参数的实验研究

目的:优化骨组织工程研究中生长因子微包囊的制作参数,观察其释放规律,为更有效的利用生长因子的生物活性提供依据。方法:通过正交实验设计方法设计27组试验,采用不同组合因变量为制作参数,制作PLGA微包囊,检测相应情况下微包囊的包封率和粒径大小,制作多元回归方程。将包裹有BSA的PLGA微包囊置于恒温震荡培养箱震荡进行体外缓释试验研究。结果:各优化变量对微包囊的粒径及其包封率均有影响,包囊表面光滑,成球较好。体外能够在11天内缓慢释放。结论:正交试验设计优化PLGA微包囊制备的各项参数,回归方程对试验结果可较好的进行预测,PLGOA微包囊在体外能够长时间缓释。     

长效缓释微球制剂生产技术的发展现状

长效缓释微球是将药物溶解或分散在高分子骨架材料中的微米级别的药物释放载体,这种新剂型可以显著降低给药频率,同时大分子材料的包裹可以提高药物的稳定性,降低药物的毒副作用,目前广泛应用在蛋白多肽等药物。已有一些用于治疗糖尿病、精神病、子宫内膜异位等疾病的长效缓释微球制剂被批准上市。然而,因为微球的制备工艺繁杂、质量控制困难,至今只在少数产品上应用,现在越来越多的口服难吸收的生物药物开始产品化,长效缓释微球在提高患者依从性方面备受瞩目。本综述对目前典型的微球制备技术做出分析和评判,以期对完善微球制备工艺有所帮助。     

PLGA microsphere construct coated with TGF-beta 3 loaded nanoparticles for neocartilage formation

Polymeric microsphere system has been widely used in tissue-regeneration matrix and drug delivery systems. To apply these biomaterials as novel cell supporting matrix for stem cell delivery, we have devised a novel method for the fabrication of nanostructured 3D scaffolds that growth factor loaded heparin/poly(L-lysine) nanoparticles were physically attached on the positively charged surface of PLGA microspheres precoated with low molecular weight of poly(ethyleneimmine) (PEI) via a layer-by-layer (LbL) system. Based on a previous study, we have prepared poly(lactide-co-glycolide) (PLGA) microspheres harboring heparin/poly(L-lysine) loaded with growth factors. Growth factor loaded heparin/poly(L-lysine) nanoparticles, which were simply produced as polyion complex micelles (PICM) with diameters of 50-150 nm, were fabricated in the first step. Microsphere matrix (size, 20 approximately 80 nm) containing TGF-beta 3 showed a significantly higher number of specific lacunae phenotypes at the end of the 4 week study in vitro culture of mesenchymal stem cells. Thus, growth factor delivery of PLGA microsphere can be used to engineer synthetic extracellular matrix. This PLGA microsphere matrix containing TGF-beta 3 showed promise as coatings for implantable biomedical devices to improve biocompatibility and ensure in vivo performance.     

载荷壳聚糖微球的海藻酸钠水凝胶的制备

目的：在支架材料上引入具有控释行为的微球,旨在通过微球包裹生长因子,通过生长因子的缓慢释放从而促进种子细胞的生长分化。方法：本实验通过在海藻酸钠水凝胶中负载具有控释功能的壳聚糖微球,并通过在微球中包栽溶茵酶从而达到控制壳聚糖降解速率的功效。实验研究了不同搅拌速度下壳聚糖微球的形貌及粒径大小,通过扫描电镜对壳聚糖微球及复合支架的形貌进行了观察,通过紫外光吸收法测试了微球的载药量及包封率,并研究了壳聚糖微球在体外的降解行为等。结果：制备的壳聚糖微球表面较光滑,溶菌酶的包封率在25．78％41．89％之间,载药量在15．20％-24．44％之间。包封溶茵酶的微胶囊在降解9天后壳聚糖分子量下降了70．40％,载荷微球的复合凝胶孔洞增多,孔洞大小均匀。结论：此复合材料有望作为栽荷软骨相关生长因子的支架模型,从而解决软骨组织工程中种子细胞匮乏的问题。     

Investigations on the Physical Structure and the Mechanism of Drug Release from an Enteric Matrix Microspheres with a Near-Zero-Order Release Kinetics Using SEM and Quantitative FTIR

The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow size distributions with one size fraction comprising 70–80% of the yield. Scanning electron microscopy and quantitative Fourier transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism.