壳聚糖/聚乙二醇/聚丙烯酸复合水凝胶的制备及药物控制释放行为研究

本文以壳聚糖(CS)、聚乙二醇(PEG)和丙烯酸(AA)为原料,制备了复合水凝胶CS/PEG/PAA。研究了负载四种具有不同结构和性质的药物(烟酸、烟酰胺、异烟肼和5-氟尿嘧啶)的复合水凝胶CS/PEG/PAA的药物控制释放行为。结果表明,烟酰胺和异烟肼在pH=1.80的缓冲溶液中的药物累积释放率(R)大于其在pH=6.86的缓冲溶液中的释放率;烟酸却在pH=6.86的缓冲溶液中的药物累积释放率(R)大于其在pH=1.80的缓冲溶液中的释放率。而5-氟尿嘧啶在两种缓冲溶液中的药物累积释放量相当。因此,复合水凝胶CS/PEG/PAA也许可以作为一种新型释放药物的载体。     

α,β-聚[N-(丁二酸基)-L-天冬酰胺]的合成及其顺铂大分子药物的细胞毒性

L-天冬氨酸在H2O/三乙胺混合溶剂中直接均相开环聚(L-天冬酰亚胺)(PSI), 合成α,β-聚[N-(丁二酸基)-L-天冬酰胺](PSAA). 研究了H2O和三乙胺的混合体积比对反应物溶解性能的影响, 并用FTIR和1H NMR表征了PSAA的结构. 以PSAA和α,β-聚(L-天冬氨酸)(PAsp)为载体, 与顺式二氯二氨合铂(Ⅱ)(CDDP)络合, 合成了PSAA-CDDP和PAsp-CDDP大分子药物. 结果表明, 载体PSAA和PAsp对Bel7402细胞的毒性均低于同浓度的聚赖氨酸; PSAA-CDDP的水溶性良好, 载药量较高, 达到了14.6%, 其药物控制释放性能较好; PSAA-CDDP和PAsp-CDDP的细胞毒性随着其浓度的增大而增大, 且细胞毒性PAsp-CDDP相似文献   

温度敏感型树枝状大分子衍生物的合成及药物控制释放

通过加入偶联剂活化末端羧基基团进行酰胺化反应, 将得到的带有羧基末端基团的温敏性聚N-异丙基丙烯酰胺接枝到整代的树枝状大分子聚酰胺-胺(PAMAM)上, 制备了树枝状大分子衍生物PAMAM-g-PNIPAm, 通过FTIR和¹H NMR表征其结构, 通过GPC和¹H NMR测定其分子量, 从而验证了接枝产物的形成; 通过紫外-可见分光光度计测定其在不同pH值缓冲液中的低临界溶胀/溶解温度(LCST)值, 发现产物的LCST值受缓冲液pH值的影响很大, 接枝前后的LCST值也发生了变化. 选用难溶性药物吲哚美辛作为模型药物, 考察了树枝状大分子及其温度敏感性衍生物PAMAM-g-PNIPAm作为载体对药物的包载、增溶和不同温度环境下的释放行为. 结果表明, 树枝状大分子衍生物对吲哚美辛具有增溶和控制释放的性能, 在难溶性药物的控制释放领域具有广阔的应用前景.     

5-氟尿嘧啶在pH敏感型分子筛控释载体中的缓释行为

以肠溶性的羟丙基甲基纤维素邻苯二甲酸酯(HPMCP)作为包覆材料,制备了HPMCP包覆的SBA-15介孔分子筛药物控释载体(HPMCP/SBA-15),并考察了抗癌药物5-氟尿嘧啶(5-Fu)负载于控释载体后,在不同pH释放环境中的释放行为.结果表明,在模拟胃液中(pH=1.2),HPMCP能明显地延缓5-Fu的释放速度;药物释放4h后,其释放率仅为15%.而在模拟肠液中(pH=7.5)HPMCP迅速溶解,对5-Fu释放速度的影响甚微;药物释放4h后,释放率可达到80%.与此同时,包覆膜的干燥温度影响5-Fu的释放行为,干燥温度越高,药物在模拟胃液中的释放速度越慢.     

侧链含5-氟尿嘧啶甲壳胺的合成及其抗肿瘤活性的研究

本文报道了以不同分子量的甲壳胺为载体,制备了侧链含5-氟尿嘧啶的一系列高分子载体药物;通过定氮分析测定了H_2N-基的反应率;由IR、UV和~(13)C-NMR确定了载体药物的结构;模拟生理条件考查了在不同pH的缓冲溶液中5-氟脲嘧啶或其衍生物的水解释放率。体外初步实验结果表明,具有Ⅰ和Ⅱ结构的载体药物对艾氏腹水癌细胞有较强的杀伤作用。     

含5-氟尿嘧啶的羧甲基纤维素钠/聚(N-异丙基丙烯酰胺)半互穿网络水凝胶的药物释放性能

以5-氟尿嘧啶(5-FU)为模型药物,对羧甲基纤维素钠/聚(N-异丙基丙烯酰胺)半互穿网络水凝胶(CMC/PNIPA semi-IPN)的药物释放性能进行了研究。结果表明:在37℃、pH=7.4时,药物的释放速率以及释放量都随着凝胶中羧甲基纤维素钠含量的增加而增大。在25℃时,pH对药物释放速率的影响较小;而在37℃时,药物释放速率受pH的影响较大。该凝胶体系用做5-FU的口服释放载体具有较佳的释放性能。     

应用FRAP技术评价蛋白在聚丙烯酰胺-丙烯酸凝胶中的扩散行为

药物分子从药物载体中的释放行为与载体的结构有密切关系.本实验中采用丙烯酰胺和丙烯酸等材料,运用水相沉淀的方法,制备了4种不同单体配比的聚丙烯酰胺-丙烯酸(P(Am-co-Ac))共聚物水凝胶.运用红外分析方法对P(Am-co-Ac)组成进行表征.使用荧光漂白恢复法(FRAP,fluorescence recovery after photobleaching)观察荧光素FITC标记的牛血清白蛋白(BSA)在聚丙烯酰胺-丙烯酸中的扩散行为,并以激光共聚焦显微镜进行实时成像.实验表明,FITC-BSA在不同单体配比的共聚物中的扩散系数是不同的.通过调节聚合物中单体的配比能够达到控制蛋白释放速率的作用,从而为调控蛋白和多肽类药物的缓控释放提供了可能性.     

两亲性树枝状大分子作为药物缓释载体的研究

利用胆酸对1代聚酰胺-胺树枝状大分子进行修饰,得到两亲性树枝状大分子(PAMAM1-CA6)。采用1H-NMR和酸碱滴定法测得每个1代PAMAM分子上共价键连了6个胆酸分子。PAMAM1-CA6在水相中自组装成纳米粒子,粒径约为273nm。以抗癌药物氨甲喋呤为模型考察了此两亲性树枝状大分子对药物的缓释行为。在碱性条件下(pH=10),PAMAM1-CA6对氨甲喋呤的释放较为缓慢;随着溶液pH的降低,药物的释放速率明显加快。说明PAMAM1-CA6对氨甲喋呤的释放具有环境响应性。体外细胞实验的结果表明,PAMAM1-CA6能够显著地提高氨甲喋呤的疗效。因此,这类由低代树枝状大分子制得的材料有望成为新型的药物控释载体。     

PVA/P(AA-AM)水凝胶的制备及药物控制释放性能研究

以聚乙烯醇(PVA)、丙烯酸(AA)和丙烯酰胺(AM)为单体,过硫酸铵(APS)为引发剂、N,N'-亚甲基双丙烯酰胺(MBA)为交联剂,通过化学引发聚合制备互穿水凝胶PVA/P(AA-AM);用红外光谱(IR)、热重分析(TG)、差示扫描量热法(DSC)及扫描电镜(SEM)等测试方法对其进行了表征,并对其溶胀性能、p H敏感性以及离子强度对溶胀性能的影响进行了研究;并考察了该凝胶分别在p H=6.86和p H=1.80介质中对药物异烟肼和烟酸的控制释放行为。结果表明,PVA/P(AA-AM)水凝胶具有良好的p H、离子强度敏感性,在两种介质中异烟肼的累积释放率均高于烟酸,但异烟肼在p H=1.80的介质中的释放速度和累积释放率均高于其在p H=6.86的介质,烟酸则结果恰好相反。所以这种水凝胶有望用作靶向药物释放的载体。     

聚(乳酸-羟基乙酸)共聚物涂层的释药性能

以乙酸乙酯为溶剂,配制聚(乳酸-羟基乙酸)共聚物(PLGA)雷帕霉素溶液,利用滴涂法在316L不锈钢表面制备PLGA载药涂层。于37℃磷酸盐缓冲液(PBS)中进行体外动态药物释放,并用紫外-可见分光光度计测定药物释放量。结果表明:PLGA涂层中PLGA分子量越小,羟基乙酸(GA)含量越高,药物释放越快;药物释放量与滴涂量呈线性关系,药物释放率与滴涂量的倒数呈线性关系;涂层中药物含量增加,其释放量也随之增加,而药物释放率先增加后降低。     

交联烯丙基葡聚精凝胶固定化脂肪酸的研究

本文研究了烯丙基葡聚糖和N、N＇－亚甲基双丙烯酰胺经反相悬浮聚合包埋固定化脂肪酶的方法。考察了悬浮介质、交联度对固定化酶的影响，得出了包埋固定化脂肪酶的最佳条件；并测定了固定化脂肪酶的催化性能，确定了该固定化酶催化橄榄油水解的最适条件。     

THE EFFECT OF CATIONIC,ANIONIC, AND NONIONIC SURFACTANT MICELLES ON THE ALKALINE HYDROLYSIS OF ESTERS

The alkaline hydrolysis of aromatic and normal aliphatic acid esters has been studied at 25°C in micellar solutions of surfactants (DTAB, TTAB, CTAB, SDS, Brij 35 and Triton X—100) with UV spectrophotometry and the method of thermokinetics in this paper. The rate constants of the alkaline hydrolysis of esters in micellar pseudophase, k_1m and K_2m have been calculated, respectively. The ratios of k_2m to k_2w or k_1w to k_1w indicate that the alkaline hydrolysis of esters arc inhibited by all of the surfactants investigated. It was supposed that such inhibition is mostly in relation to the micropolarity of micellar surface. The critical micellar concentrations of the corresponding systems have also been measured with the conductivity method and UV spectrophometry in this paper.     

增塑剂对可吸收缝合线后处理工艺条件和降解性能的影响

分别在对二氧环己酮均聚物和对二氧环己酮-乙交酯共聚物中加入增塑剂进行纺丝,制得聚对二氧环己酮单丝缝合线(PDS)和对二氧环己酮-乙交酯共聚物单丝缝合线(PDG).用DSC方法研究了增塑剂含量对PDS缝合线热性能的影响和不同热定型条件的PDG缝合线的热性能,测试了热定型温度对PDG缝合线初始强度、模量及柔量的影响,考察了增塑剂含量对两种缝合线的生物降解性能和力学降解性能影响.研究结果表明,PDS缝合线的玻璃化转变温度Tg、结晶温度Tc以及熔融温度Tm均随着增塑剂含量的增加而降低,但其结晶能力增加.随着热定型温度的增加,PDG缝合线的初始打结强度、熔融热均提高,熔融温度Tm基本保持不变.两种缝合线的强度保留率随着增塑剂含量的增加均先增加后减小,而重量保留率随着增塑剂含量增加始终减小.     

THE SUBUNIT STRUCTURE OF YEAST DNA PHOTOLYASE AND THE PURIFICATION OF A FLUORESCENT ACTIVATOR OF THE ENZYME

Abstract— Yeast DNA photolyase purified twice by affinity chromatography was analyzed by electrophoresis on polyacrylamide gradient gels or by sedimentation velocity through 5–200/, sucrose gradients containing 0.4MKC1. Its molecular weight estimated by both these methods was 130 ,000 and 136 ,000, respectively. However, the enzyme dissociated into two bands having molecular weights of 60 ,000 and 85 ,000 when it was examined by electrophoresis on SDS polyacrylamide gradient gels. The subunit structure of the enzyme was confirmed when two absorption maxima corresponding to polypeptides of 54 ,000 and 82 ,500 daltons were observed in sucrose gradients run in 1.0 M KCI. Upon mixing these two fractions, a time-dependent increase in activity occurred, demonstrating that active enzyme could be reconstituted from these subunits.
The activity of photolyase purified by affinity chromatography is enhanced by a compound (activator III) obtained from yeast by acidification, neutralization, ion exchange chromatography and gel filtration. Activator III emits at 350 and 440 nm when excited at 290 nm, and emits at 440 nm when excited at 358 nm. After acid hydrolysis, emission at 440 nm is produced only by excitation at 358 nm, indicating that it contains two separate chromophoric moieties. The chromophore excited by 358 nm light has a pK of 9–11, while the other has a pK of 4–5. Enhancement of photolyase activity by activator III at a concentration equimolar with that of the enzyme and the similarity of the fluorescent spectra of the activator and heat-denatured photolyase suggest that the activator may be the chromophore associated with the enzyme.     

INTERPLAY OF STERIC AND ELECTRONIC INFLUENCES IN THE CHEMISTRY OF MONOCYCLIC AND BICYCLIC PHOSPHORUS ESTERS

Abstract

The importance of biologically active cyclic phosphorus systems has become increasingly apparent relatively recently; particularly, for example, with the discoveries of the cellular “second messenger” activities of cyclic 3′, 5′-adenosine and guanosine monophosphates and the powerful cancer therapeutic capabilities of cyclo-phosphamide and its cyclic metabolites. The earlier recognition that cyclic 2′, 3′-nucleotides formed as intermediates in the hydrolysis of polynucleotides, led to the classic researches of Westheimer and his coworkers on the hydrolysis rates of cyclic and acyclic phosphate esters.¹ Within the few years the extreme toxicities of bicyclic phosphorus esters compared to their acyclic analogues have come to light^2,3 along with the surprising observation that the cholinesterase inhibition of such cages is only negligible.^3,4     

低温条件下二氧化碳存在时羰基硫催化水解本征动力学

在自行设计和安装的一套微反-色谱联用装置上，以TGH为催化剂，进行了二氧化碳对羰基硫催化水解本征动力学影响的研究，得出了在低温50 ℃～70 ℃、高水汽摩尔比(H2O/COS=60～550)，分别对原料气中有无存在CO2的条件下,采用非线性Marquart法对实验数据进行回归，所建立的本征动力学方程式为：     

高分子药物学的研究进展与期盼

自从20世纪70年代提出高分子前药的概念以来,伴随着纳米技术的发展,"高分子药物学"作为高分子科学和材料学、纳米科学、药物学、临床医学、分析科学的交叉学科,正在悄然形成.本文综述了近年高分子药物在药物化学、制剂学、药效学等方面所取得的进展,概述了高分子药物的药理学和药代动力学与小分子药物的区别与联系,指出了高分子药物药效学、药理学和药代动力学研究中的难题和瓶颈,特别是高分子药物可能存在的"三种状态"及从"纳米颗粒药"到"单个高分子药"再到"小分子药"的转变,分析了高分子药输送过程中存在的多重屏障如毛细血管壁、细胞外基质和细胞壁等,阐述了高分子药物的"生理靶向"和"EPR"效应的竞争,指出了高分子药在靶向输送和逆转耐药方面的优势,强调了发展相关分析方法的必要性,期盼高分子科学家与药物学家进行真诚有效的合作,大力促进我国高分子药物学和高分子药物产业的创新和发展.     

树脂吸附法制备固定化乳糖酶及其操作稳定性的研究

利用树脂吸附并结合包埋与交联的方法进行微生物胞外乳糖酶的固定化。固定化乳糖酶体现了良好的操作稳定性。以5%乳糖溶液为底物,分批反应11次后,乳糖水解率仍保持85%以上;在填充床反应器中进行连续水解乳糖实验,反应62天后,乳糖水解率保持在80%。     

HYDROLYSIS TRANSFORMATION OF A POLYSTYRENE—b—POLY（tert—BUTYL ACRYLATE） COPOLYMER AND MICELLIZATION PROPERTIES OF THE HYDROLYZED COPOLYMER

A very mild and extremely efficient hydrolysis method for transformation of polystyrene-b-poly(tert-butyl acrylate)(PS-b-PtBA)to polystyrene-b-poly(acrylic acid)(PS-b-PAA) was designed and carried out using more convenient and inexpensive chlorotrimethylsilane/sodium iodide as reagents.The hydrolysis product can self-assemble in aqueous media to give regular micelles with PS block forming the core and PAA block forming the corona,or in tetrahydrofuran (THF) to give reverse micelles with the hydrophilic block in the core.     

THE INVESTIGATION OF DIBENZTHIOPHENE AND DIBENZTHIOPHENDIOXIDE DERIVATIVES SYNTHESIS METHODS

Abstract

The polymeric materials containing thiophene units possess a number of important properties including the increased thermal stability. Thus we have developed the methods of synthesizing the diamino-, dioxy-, and tetraamino-derivatives of dibenzthiophene (DBT) and dibenzthiophendioxide (DBTD), which find their application as monomers for polymeric materials. The synthesis of these monomers was carried out with halogen-substituted DBT DBTD on Cu catalysts by ammonolysis and hydrolysis reactions and also by consecutive nitration, ammonolysis and catalytic reduction reactions.