Novel bioresorbable hydrogels prepared from chitosan‐graft‐polylactide copolymers

A series of biodegradable chitosan‐graft‐polylactide (CS‐g‐PLA) copolymers were prepared by grafting of poly(L ‐lactide) (PLLA) or poly(D ‐lactide) (PDLA) precursor to the backbone of chitosan using N,N′‐carbonyldiimidazole as coupling agent. The composition of the copolymers was varied by adjusting the chain length of PLA as well as the ratio of chitosan to PLA. The copolymers synthesized via this ‘graft‐onto’ method present interesting properties as shown by NMR and infrared spectroscopy, gel permeation chromatography and solubility tests. Hydrogels were prepared by mixing water‐soluble CS‐g‐PLLA and CS‐g‐PDLA solutions. Gelation was assigned to stereocomplexation between PLLA and PDLA blocks as evidenced by differential scanning calorimetry and wide‐angle X‐ray diffraction measurements. Thymopentin (TP5) was taken as a model drug to evaluate the potential of these CS‐g‐PLA hydrogels as drug carriers. An initial burst and a final release up to 82% of TP5 were observed from high‐performance liquid chromatography analysis. Copyright © 2011 Society of Chemical Industry     

固相合成胸腺五肽的分离与纯化

胸腺五肽(TP5)是一种很有发展前景的药物,具有胸腺素的全部生理功能。固相合成法是胸腺五肽生产的主流技术,目前,对固相合成的五肽一般采用反相色谱技术纯化,但效率低、成本高,仅限于小规模制备。实验采用离子交换法纯化,并进行了方案优化,发现在pH4 4醋酸盐缓冲液平衡、盐梯度洗脱条件下纯化TP5,一步分离纯度可达98 23%。该法可以满足大规模制备的要求,且成本很低。     

茶袋法固相合成胸腺五肽肽库

利用组合化学技术,采用简便的茶袋法固相合成制备胸腺五肽D型氨基酸取代类似物肽库,共合成32条肽。粗肽得率平均在54%左右。通过高效液相色谱分离得到纯肽,经质谱及HPLC分析,所制类似物相对分子质量与胸腺五肽一致,精制后的肽得率平均在36%左右。     

固相合成胸腺五肽的研究进展

叙述了胸腺五肽TP5的药理、药代及毒副作用、市场状况和前景，分析了胸腺五肽各氨基酸的α－氨基保护基和侧链保护基的特点，并从固相载体、第一个氨基酸的连接、肽链延长等3个方面介绍了Merrifield法、Boc法、Fmoc法，3种方法合成胸腺五肽的过程。     

胸腺五肽分子印迹聚合物磁性微球的制备及吸附性能研究

以胸腺五肽(Tp-5)为模板分子、丙烯酰胺(AM)为功能单体、乙二醇二甲基丙烯酸酯(EGDMA)为交联剂、羧基功能化Fe3O4磁性粒子为载体,采用乳液聚合法制备出胸腺五肽分子印迹聚合物磁性微球(Tp-5-MIPMMs)。通过研究交联剂用量、预聚合时间、聚合反应时间对Tp-5-MIPMMs吸附性能和印迹因子的影响,确定了最佳制备条件。扫描电镜(SEM)分析显示微球表面被多孔、均匀聚合物包覆,粒径40μm左右。静态和动态吸附研究表明Tp-5-MIPMMs在2.0 g·L-1的Tp-5溶液中吸附8 h达到饱和,最大吸附量达15.63 mg·g-1,印迹因子达1.51。以谷胱甘肽(GSH)作对比,用薄层色谱(TLC)研究了Tp-5-MIPMMs的选择吸附性能,结果表明Tp-5-MIPMMs对Tp-5分子具有特异选择能力。     

Fmoc法固相合成胸腺五肽工艺

采用Fmoc法固相合成胸腺五肽(TP-5)。利用RP-HPLC和质谱对其进行鉴定,绘制胸腺五肽纯品的标准曲线,作为胸腺五肽的准确定量方法。考察不同的反应溶剂、缩合剂和切割条件对合成胸腺五肽纯度的影响,并由此确定最佳合成工艺条件:以DMF为反应溶剂,HATU为缩合剂,TFA、p-甲基苯酚、EDT和H2O体积比为97.00∶0.25∶0.25∶2.50溶液为切割条件。在此条件下,胸腺五肽的纯度达到80.34%。     

Carbamazepine/βCD/HPMC Solid Dispersions. I. Influence of the Spray-Drying Process and βCD/HPMC on the Drug Dissolution Profile

Abstract

The aim of this study was to compare carbamazepine (CBZ) solid dispersions prepared by spray-drying of aqueous dispersions with the corresponding physical mixtures. The influence of the association of β-cyclodextrin (βCD) and hydroxypropyl methylcellulose (HPMC) on the CBZ dissolution profile of the preparations was investigated. Results demonstrated that CBZ release from solid dispersions is dependent on the ratio of βCD and HPMC. The spray-drying process confers better homogeneity to CBZ polymeric dispersions than the physical mixture process. In summary, we demonstrated the feasibility of obtaining a homogeneous polymeric solid dispersion of CBZ from an aqueous media by spray-drying and a clear influence of the βCD:HPMC ratio on the release profile of CBZ.     

胸腺五肽对产科危重症患者免疫调理治疗的随机对照研究

目的：研究产科危重病人CD3^＋、CD4^＋,CD8^＋、NK细胞记数、CD4^＋／CD8^＋、α白细胞介紊-6（IL-6）和肿瘤坏死因子α（TNF—α）的变化,探讨胸腺五肽（Thymopentin,TP-5）对产科重症病人的免疫调理作用。方法．2005年1月至2007年12月71例收住重庆医科大学附属第一医院中心ICU的产科重症病人随机分为对照组和治疗组,两组分别于治疗后1、5、10d检测CD3^＋、CD4^＋、CD8^＋和NK细胞数;于治疗前和治疗后1、5d测定病人血清IL-6和TNF—α的动态变化。结果：TP-5免疫调理治疗后两组病人T淋巴细胞总数和亚群在第5d开始有显著性差异,治疗组CD8^＋低于对照组,CD4^＋、NK细胞和CD4^＋／CD8^＋比值高于对照组（P〈0．05）。第10d治疗组CD3^＋、CD4^＋、NK细胞和CD4^＋／CD8^＋比值高于对照组,CD8^＋细胞低于对照组（P〈0．05）。治疗组血清IL-6在第5d下降（P〈0．05）。TNF—α在第1d开始低于对照组（P〈0．03）,下降在第5d显著下降（P〈0．05）。结论：TP-5能明显调节产科危重病人免疫功能,使之趋于平衡,并最终获得改善预后的效果。且副反应少,可作为良好免疫调节剂用于产科危重病人综合治疗。