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。     

胸腺五肽的固相合成

采用哌啶脱Fmoc法固相合成胸腺五肽,通过采用Fmoc保护的Wang树脂,利用紫外-可见光分光光度法测量树脂上裸露氨基的含量,从而定量监测脱保护反应发生的程度以及树脂的取代率.目标产物经高效液相和质谱表征分析,该胸腺五肽产物产率为88.67％,纯度为98.54％.该研究采用的哌啶脱Fmoc法固相合成胸腺五肽取代率较高,...     

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。     

Fmoc法固相合成胸腺五肽的工艺研究

固相合成法是胸腺五肽生产的主流技术。本文采用对碱敏感的Fmoc保护Na-氨基。用二甲基甲酰胺为溶剂合成胸腺五肽。本文阐述了其基本原理、采用此法的原因、合成工艺及纯化方法。     

胸腺五肽配合化疗治疗中晚期恶性肿瘤

目的观察胸腺五肽配合化疗治疗中晚期恶性肿瘤的疗效。方法将60例中晚期恶性肿瘤患者分成三组,两组使用化疗加每天不同剂量的胸腺五肽,另一组单纯化疗,观察用药前后的近期疗效,KPS评分和免疫指标。结果治疗组T细胞亚群指标明显高于对照组;近期疗效,KPS评分三组无明显差别;而使用不同剂量胸腺五肽的治疗组间差别不明显。结论胸腺五肽是一种能够较好提高恶性肿瘤患者生活质量的辅助用药。     

胸腺五肽对恶性肿瘤患者输血后细胞免疫功能的影响研究

目的:输血是恶性肿瘤临床治疗的常用策略,而含有白细胞的血液制品会抑制免疫功能.胸腺素是一种免疫调节多效细胞因子,用于癌症或感染性疾病患者,提示其对癌症手术切除患者输血疗效的影响.本研究旨在探讨胸腺素在恶性肿瘤患者输血中的免疫调节作用.方法:本研究纳入80例结直肠癌患者(男47例,女33例).将患者随机分为输注无白细胞混...     

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%。     

胸腺五肽固相合成及免疫增强作用的研究

目的　合成有生物活性的胸腺五肽并研究其免疫增强作用。方法　用Fmoc固相肽合成法合成胸腺五肽 ,用E玫瑰花实验检测生物活性。合成的胸腺五肽经小鼠腹腔注射后进行淋巴细胞转化实验、溶血空斑实验及IL 2活性实验 ,研究其免疫增强作用。结果　合成 2批胸腺五肽 ,精肽产量分别为 2 7mg和 3 4mg ,具有生物活性 ,实验组动物脾淋巴细胞的转化率、空斑形成细胞及IL 2活性皆明显高于空白对照组。结论　用Fmoc固相肽合成法可以成功地合成有生物活性的胸腺五肽 ,且具有免疫增强作用。     

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。     

正丙基膦酸酐的合成及其在胸腺五肽合成上应用

在研究现有正丙基膦酸酐合成工艺的基础上,以溴代正丙烷与亚磷酸二乙酯为起始原料经烷基化酸解与脱水缩合三步反应得到高含量正丙基膦酸酐。将其作为脱水剂应用于胸腺五肽(TP5)的合成,与常规二代缩合剂HBTU(苯并三氮唑-N,N,N’,N’-四甲基脲六氟磷酸盐)相比,具有脱水效率高,后处理方便等优点。     

A Calculation Procedure for Designing Ideal Centrifugal Separation Cascades

Abstract

A numerical method is presented for determining flow rates in centrifugal isotope separation cascades that satisfy the required “ideal cascade” conditions. This method is an iterative method, which in the iteration process uses the q-iteration method to give the concentration and distributions of components under a specified hydraulic status for a cascade; and then, based on the concentration distributions, solves the algebraic equations describing the hydraulic status of the cascade to improve the specified hydraulic status towards the required “ideal cascade” conditions. The material losses in the cascade pipes and centrifuges are taken into account. Numerical simulations are performed by taking an MARC cascade with variant stage separation factors as an example. The results from four cases with and without material losses are compared. The results demonstrate that the method works very well, and show that when the material losses are nonexistent or very small, the concentration distributions can exactly satisfy the “ideal cascade” condition; but when the material losses are large, the “ideal cascade” condition can not be satisfied, but the method can produce a solution that allows the condition to be approximately satisfied.     

葡萄球菌蛋白A的纯化新工艺

目的建立一种高效、简便、实用的分离纯化葡萄球菌蛋白A(SPA)的工艺。方法采用超声波破菌和IgG-Sepharose4B亲和层析分离纯化SPA;以Lowry法检测蛋白含量;双向琼脂免疫扩散法测定效价和特异性;用还原和非还原SDS-PAGE法检测纯度和相对分子质量。结果此法制得的3批SPA的蛋白含量分别为4·7、4·4和5·4mg/ml,收率分别为2·70、2·64和3·78g/100g湿菌。对人IgG的免疫双扩散效价均为1:64;与正常人、豚鼠、家兔和小鼠的血清反应均出现一条沉淀线,而与鸡和羊不出现沉淀线。经非还原SDS-PAGE检测只呈现一条蛋白带,相对分子质量约为160000～180000;经还原SDS-PAGE检测呈现两条蛋白带,相对分子质量分别约为67000和34000。结论已成功建立了分离纯化SPA的新工艺。     

一种新颖的酮洛芬合成工艺

针对传统工艺时间较长,容易产生自身缩合副产物的问题,本工艺以腈乙基二苯甲酮为原料,经碱性条件下水解得酮洛芬。反应时间从10h缩短为1h,副反应少,原料转化率高,产品收率达99%以上。     

A Novel Procedure of Hydrogen Isotope Separation Based on Chemical Exchange and a Selective Permeable Membrane

Abstract

It is shown theoretically that a novel process of hydrogen isotope separation can be obtained by combining bithermal isotopic exchange with transport through a selective permeable membrane. The theory of the process predicts that a small column with high separation and very small inventory can be realized. The method is attractive especially for small and medium scale processes, such as tritium enrichment, heavy water upgrading, and final deuterium concentration.     

在NaOH-烯丙基氯-DMSO体系中合成烯丙基蔗糖的新方法

Allylsucrose has been prepared by reaction of sucrose with allyl chloride in the NaOH-DMSO system. DS^↑- （average degree of substitution） of allylsucrose calculated by elemental analysis was 6.7, and the efficiency of allyl chloride was 83.7%. The mechanism of the reaction was based on the acceleration of base-catalyzed reactions in dipolar aprotic solvents. The novel method is facile and suitable for large-scale preparation.     

浓度极稀物中回收微量重组分的精馏操作策略-准间歇精馏

A new operation policy-quasi-batch distillation for recovering infinitesimal amounts species existing in a mixture is presented. In quasi-batch distillation operation, feed is introduced with a constant flow rate onto the feed stage of the column, and the flow rate of the distillate is the same as that of the feed, whereas the bottom product is withdrawn periodically. The behavior of quasi-batch distillation is simulated and analyzed through an example on heavy water separation. Comparing with continuous or batch distillation, the new operation policy is more reliable and efficient to achieve higher recovery of dilute component. This is especially suitable for separating small amount of precious species from large amount of raw material.     

从发酵液中分离提取5-氨基乙酰丙酸盐酸盐的新工艺

5-氨基乙酰丙酸(ALA)在农业、医学等领域应用广泛,市场前景广阔。今采用膜分离、反应萃取和浓缩结晶相结合的新工艺从发酵液中提取5-氨基乙酰丙酸盐酸盐(ALA·HCl),有效提高了产品的回收率,降低了生产成本。分离过程中先对离心后的发酵液进行超滤除杂,反渗透浓缩,预处理过程ALA回收率为86.4%;然后以体积比1:1的磷酸二(2-乙基己基)酯-正己醇混合液为萃取剂,20℃下进行二级萃取。初始水相pH6.5,两次萃取有机相和水相的体积比R均为0.5;两级萃取所得的有机相混合后,再在30℃下用1mol·L-1盐酸对有机相进行反萃取,水相和有机相的体积比r为0.5。萃取过程ALA的回收率为79.8%。所得反萃水相经脱色、真空蒸发浓缩后二次冷却结晶。分离过程ALA·HCl的总收率达到55.2%,产品纯度大于99.5%。     

A Rapid Procedure for the Quantitative Separation of α,ε-Diaminopimelic Acid (DAP)

Abstract

A simple and rapid procedure for the quantitative separation of α,ε-diaminopimelic acid (DAP) from mixture of amino acids, using anion-exchange resin, is presented. The recovery of DAP from the column ranges between 96 and 98%.     

A Laboratory Decanting Procedure to Simulate Whole Stillage Separation in Dry-Grind Corn Ethanol Process

In the dry-grind corn ethanol industry, horizontal decanter centrifuges are used to separate the whole stillage into wet grains and thin stillage. The wet grains mixed with condensed thin stillage are dried to form dried distiller’s grains with solubles (DDGS). In order to investigate the effect of different corn breaking treatments on increasing oil partitioning in thin stillage, a laboratory method is needed to simulate industrial decanting where a typical thin stillage is produced. The thin stillage obtained using a conventional laboratory centrifuge had much lower solids content and less than one-half of the dry-matter yield compared to the industry counterpart because the conventional laboratory centrifuge and industry decanter centrifuge have different separation mechanisms. By evaluating the properties of industrial thin stillage and the mechanism of industrial decanter centrifugation, a laboratory decanting device was designed and a decanting procedure, the multiple-wash centrifugal filtration (MWCF) method, was developed. This method involves multiple steps of filtration under centrifugal force after washing the solids with the liquid generated from the same mash. Four cycles of MWCF produced a thin stillage with similar solids content (7.3 vs. 7.2%), dry-matter yield (54.2 vs. 54.7%), and wet yield (83.3 vs. 80.6%) compared to industrial thin stillage. The presence of ethanol did not influence the laboratory decanting results, which indicates the application robustness of this laboratory thin stillage preparation method.     

Separation of Radionuclides on Mesoporous Zirconium Silicate: A Novel Sorbent

Abstract

Five different samples of mesoporous zirconium silicate have been prepared with various mole ratios of Si/Zr and Cetyltrimethylammonium bromide (CTMABr) as template. XRD, nitrogen sorption, SEM, IR, thermogravimetry and sorption of radionuclides have been studied. Separation of Cs(I)-Mo(VI), Sr(II)-Mo(VI), Cs(I)-Th(IV), Sr(II)-Th(IV), and Tl(I)-Th(IV) have been developed on columns of this novel sorbent.