蛋白质、多肽类药物控制释放体系的研究

近年来,蛋白质、多肽类药物广泛应用于各类疾病的治疗。本文对聚乙二醇修饰的蛋白质及蛋白质类药物控制释放这两大体系的研究进展做了较系统的总结和评述,并就更高级的靶向、易吸收的蛋白质药物体系的发展进行了展望。     

Characterization of Controlled Release Fertilizer by Infrared Microspectroscopy

The feasibility and potential of infrared microspectroscopy for quantitatively characterizing the dynamic changes in the coating of controlled release fertilizer granules are discussed to better characterize the release of nutrients. Two polymer-coated compound fertilizers were selected as typical samples. A frozen section technique was used for sample pretreatment, where freeze-dried controlled release fertilizer granules were cut into 20-µm-thick sections. Optimal parameters for the spectral range, spectral resolution, and pixel dimensions in the transmission spectra were determined to be 4000–750?cm^?1, 16?cm^?1, and 6.25?×?6.25?µm, respectively. A mean spectrum of four scans was used in data processing for second-derivative analysis with nine smoothing points. This work is aimed to quantitatively distinguish between the coating and fertilizer core according to radial variations in second-derivative spectra using characteristic wavelengths that represent the coating and fertilizer core. During nutrient release, the fertilizer core gathered gradually and adhered in uniform distribution around the coating, while some nutrients were trapped in micropores. The coating thickness of the controlled release fertilizers fluctuated within 37.5––55 and 15–55?µm, respectively. Although measurement results based on infrared microspectroscopy were in accordance with the scanning electron microscopy observations, they were shown to be more accurate and were not influenced by the coating mixed with the fertilizer core. Furthermore, infrared microspectroscopy was effectively used to quantify the dynamic thickness of the coating of controlled release fertilizer granules and visually characterize fertilizer penetration through the coating.     

带有可调通道的嵌段共聚物胶束对药物的控制释放

用聚丙烯酸叔丁酯-b-聚乙二醇(PtBA45-b-PEG114)和聚丙烯酸叔丁酯-b-聚4-乙烯基吡啶(PtBA60-b-P4VP80)制备了复合胶束. 该胶束在pH=2.5的酸性水溶液中形成以PtBA为核, PEG和P4VP为壳的稳定球型结构. 在pH=12时, 壳层的P4VP链段变为疏水, 塌缩在PtBA的核上形成内壳, PEG链段继续保持溶解状态, 与成核的PtBA连接并穿过塌陷的P4VP内壳, 形成胶束的冠, 由于PEG处于溶解状态, 其分子链间有比较大的空隙, 可以控制一些小分子通过, 在胶束的表面形成通道. 该通道类似于生物膜的蛋白通道, 可以控制PtBA核与外界进行能量或物质交换的速度. 以布洛芬为模型分子, 负载在胶束内进行药物控制释放研究的结果表明, 胶束表面的通道可以起到明显控制布洛芬释放速度的作用, 并且药物的释放速度与通道在胶束表面的比例成正比.     

甲醇-水混合溶剂后处理制备丝素蛋白膜及其药物释放研究

采用溶液浇注法制备丝素蛋白薄膜, 应用傅里叶红外光谱(FTIR)和X 射线衍射(XRD)研究了浓度不同的甲醇-水混合溶剂处理后丝素蛋白薄膜的结构变化, 并以罗丹明B 为模型药物与丝素蛋白构建药物缓释体系, 考察了丝素蛋白膜的结晶结构对药物释放动力学的影响. 结果显示, 在甲醇体积比浓度Φ_MeOH＝50%～90%的范围内, 丝素蛋白材料中以β-折叠为主的silk Ⅱ 结晶含量随着混合溶剂中甲醇浓度的增加而先增加后下降, 在Φ_MeOH＝80%附近出现最大值. 罗丹明B 从丝素蛋白膜的释放属于Fickian 扩散机理, 其扩散指数n 随着丝素蛋白膜中β-折叠含量的增加而增加, silk Ⅱ结晶是丝素蛋白材料药物释放的天然调节器.     

PNIPA类纳米水凝胶在药物缓控释研究中的应用

简要介绍了聚N-异丙基丙烯酰胺(Poly N-isopropylacrylamide, PNIPA)类纳米水凝胶的性质及智能响应机理,并重点综述了近年来此类纳米水凝胶在药物缓控释研究中的应用:作为脂溶性小分子药物的载体,达到增溶及缓控释药物的效果,并增强药物的稳定性及生物活性;作为水溶性小分子药物的载体,达到缓释该类药物的效果;作为生物大分子药物(蛋白,多糖)的载体,克服直接用药时的弊端;此外,还可作为基因工程载体.     

控制药物释放体系及其机理

药物控制释放是目前药物学发展的一个重要领域,用于药物控制释放的载体一般是高分子材料。本文主要介绍药物控制释放的种类、机理、高分子材料及其应用。     

淀粉囊化农药控释缓释技术

介绍了近20年来淀粉囊化农药控释缓释技术的研究和发展概况，详细综述和讨论了淀粉囊化技术的囊化方法、影响释放特性的主要因素、制品耐水性问题的解决办法、开发应用研究及发展前景。     

温敏性抗菌水凝胶的制备与控释技术研究进展

温敏水凝胶是一类通过感知温度变化使自身发生相变的智能型聚合物凝胶,通过负载抗菌剂或抗菌性单体制备抗菌水凝胶是近年来药物控制释放、组织工程以及生物免疫等领域关注的热点。本文概述了负载抗菌剂型温敏性抗菌水凝胶的物理交联和化学交联制备技术的研究概况,着重阐述了温敏性抗菌水凝胶的孔径调控、制备材料调控、载药模式调控等技术的研究进展,并对温敏性抗菌水凝胶的控释技术应用前景,特别是在生物质材料领域的应用前景进行了展望。     

黄豆脲酶的提取及其在缓释肥料中尿素态氮测定中的应用

本文建立了准确、快速、经济的控制缓释肥料中尿素态氮的测定方法。采用自制黄豆脲酶水解液,于pH7．0的磷酸盐缓冲体系中水解尿素,以奈氏试剂为显色剂,用分光光度法测定尿素态氮。该方法在0～2．50μg／mL范围内符合比耳定律,检出限为0．01μg／mL,用于控制缓释肥料中尿素态氮的测定,回收率在96．2％到100．8％之间,与商品脲酶测定结果接近。     

Synthesis of Enantiopure α-Alkoxy-α-Trifluoromethyl Aldehydes and Carboxylic Acids from Trifluoromethyl Ketones

Formaldehyde dialkylhydrazones behave as neutral d¹ synthons in their uncatalyzed reaction with trifluoromethyl ketones (see reaction). Both racemic and optically pure 1,2-adducts were obtained in good yields. Efficient deprotection of the hydrazone moiety afforded interesting fluorinated quaternary compounds such as 1 and 2 .     

磁性微胶囊的制备及其药物缓控释性能

用乳液-凝胶法制备了磁性壳聚糖/海藻酸钠微胶囊. 在壳聚糖/海藻酸钠微胶囊中掺入Fe3O4磁性中空球, 使微胶囊具有磁靶向性能. 以头孢拉定作为模型药物研究了载药磁性微胶囊的载药量、包封率及药物缓控释性能等. 结果表明, 提高头孢拉定的初始浓度可以提高载药量, 却不利于提高药物的包封率. 所制备的微胶囊在各种缓冲溶液中长时间内具有显著的缓释效果, 并具有pH 刺激响应释放的性能, 即在模拟胃液中的药物释放率大大降低, 而在模拟体液和肠液中的释放时间大大延长, 可达50 h以上. 另外, 在外加磁场作用下, 微胶囊表现出良好的磁定向运动性能, 为磁靶向药物输送提供基础.     

荧光标记pH敏感胶束的制备及其药物控释

利用原子转移自由基聚合方法（ATRP）合成了pH敏感的两亲性嵌段共聚物mPEG-b-PDPA_n（聚合度n=100-200）及荧光修饰的嵌段聚合物异硫氰酸荧光素-聚乙二醇-聚N,N-二异丙胺基甲基丙烯酸乙酯（FITCPEG₄₅-PDPA₁₀₀）。采用溶剂挥发的方法制备胶束,此胶束呈现均一的球形分布,平均粒径180-240 nm（0.3 mg·mL^-1）。以阿霉素（DOX）为模拟药物,其胶束载药量约11%（w,质量分数）左右,外环境pH对载药胶束的粒径和体外释放行为有显著影响。在弱酸环境下,胶束核质子化发生膨胀甚至解体,在2-3 h内药物可释放80%左右。体外毒性试验表明,空白胶束与人类肝癌细胞（Huh7）有良好的生物相容性。同时,与此细胞共同孵育5 h的荧光聚合物胶束体现了较好的转染效果。因此,这类荧光标记胶束可能会为实时跟踪化疗药物的输送或分布打开新的视角。     

包膜型多功能缓/控释肥料的研究现状及进展

缓/控释肥料能够在保证粮食产量的前提下,提高养分利用率,减少肥料养分流失对环境造成的危害。包膜型缓/控释肥料对养分具有更好的控释效果,通过包膜材料的组成设计,最有可能实现养分的释放速率与作物的需肥规律相匹配。本文综述了包膜型缓/控释肥料的国内外研究现状,肥料养分的控释机理和释放性能评价方法,阐述了包膜型缓/控释肥料研究和应用中存在的问题及未来的发展趋势。     

一步法高通量可控制备生物相容水/水微囊及其响应释放

生物相容水/水微囊在药物递送、 医学治疗等领域具有重要应用. 本文通过设计同轴微流控器件, 结合数值模拟优化和流动阻力分析, 实现一步法高通量可控制备大小均匀、 尺寸可控、 壁厚可调、 生物相容的水/水微囊. 采用实验研究和数值模拟相结合的方式, 研究了微流控器件结构、 内相流速、 外相流速、 外相/空气界面张力、 内相/外相界面张力、 内相黏度和外相黏度等参数对水/水微囊直径和壁厚的调控规律. 通过微通道流动阻力分析, 设计多通道平行放大微流控器件, 实现尺寸均匀可控水/水微囊的高通量制备. 验证了生物相容水/水微囊作为活性物质的理想载体, 可以通过改变pH或溶解囊壁释放载体, 进而实现活性物质的pH响应释放, 为其实际应用奠定了基础.     

Release of toluene from micron-sized, monodispersed, cross-linked, hollow polymer particles

The release behavior of toluene from the hollow-inside, micron-sized, monodispersed, cross-linked, polystyrene/polydivinylbenzene composite particles which had various cross-linking densities and shell thicknesses was examined. The hollow particles were produced by seeded polymerization utilizing the dynamic swelling method which we proposed in 1991. In comparison with that from hollow-free particles, there was a clear difference. The cross-linking density and shell thickness of the hollow composite particles did not affect the release rate in the former period, but did it in the latter one. Received: 2 February 2000/Accepted: 30 August 2000     

可降解光交联聚酸酐与聚酰胺-甲基丙烯酰胺凝胶的合成及药物控释

合成聚酰胺-胺型树状分子（PAMAM）并进行端基甲基丙烯酰基修饰,将最外层接枝光化学活性双键,修饰产物与甲基丙烯酸酐化癸二酸(MSA)用DMSO溶解并在光引发剂存在下,经过紫外光照射得到具有一定生物相容性的凝胶。运用1H NMR和FT-IR对聚酰胺-甲基丙烯酰胺的结构进行表征。凝胶的降解实验表明,聚酸酐含量为50-60wt%的凝胶以表面溶蚀的方式降解,随着甲基丙烯酸酐化癸二酸（MSA）在凝胶中含量不同,降解时间在45~60天之间,pH在6.5-8.06范围内改变。包埋氧氟沙星凝胶的降解实验表明,可以通过改变聚酸酐的含量控制降解时间和药物释放量。     

Synthesis of Per- and Poly-Substituted Trehalose Derivatives: Studies of Properties Relevant to Their Use as Excipients for Controlled Drug Release

Per- and poly-substituted oligosaccharide derivatives, with trehalose cores, have been prepared and assessed for their potential for use as excipients in controlled-release formulations. The synthesized compounds, generally with acyl and amido substituents, included 6,6′-N,N′ -diamido-6,6′ -dideoxy-α,α -trehalose derivatives, 6,6′ -bis(1,2,3,4-tetra-O-acetyl-β -D-glucopyranuronyl)-α, α -trehalose derivatives, 2,2′,3,3′ -tetra-O-acetyl-6,6′ -bis-(1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronyl)-4,4′ -di-O-acyl-α,α-trehalose, 2, 2′, 3, 3′ -tetra-O-acetyl-6-(1,2,3,4-tetra-O-acetyl-β-D-glucopyranuronyl)-4,4′,6′ -tri-O-acyl-α,α-trehalose, and 2,2′,3,3′,4,4′ -hexa-O-acetyl-6,6′ -bis-(1,2,3,4-tetra-O-acetyl-6-O-succinyl-β-D-glucopyranuronyl)-α,α-trehalose. Compounds were characterized by NMR, IR, MS and optical rotations; elemental analyses; or HRMS. The compounds formed amorphous materials either on fast quenching of melts or on spray drying. Properties, used in the initial assessment of the potential as controlled-release excipients, were log₁₀ P and glass transition, T_g, values.     

Synthesis and Characterization of Poly(Biphenyl‐2‐yl p‐Styrenesulphonate) as Profungicide in Controlled Release Technique

A new fungicide controlled release formulation was prepared by the reaction of p‐styrenesulphonyl chloride with biphenyl‐2‐ol (Dowicide A) as fungicide. The resulting monomer containing the fungicide was polymerized with benzoyl peroxide as initiator. The monomer and the polymer were identified by spectroscopic methods, and molecular weight of the polymer was determined by GPC. Also mp, Tg and Td of the polymer were identified by DSC. The release characteristic of the polymer was studied in neutral, alkaline, and acidic media. Also, the effect of the temperature on the release of bioactive agent (Dowicide A) was investigated. The hydrolysis data showed that the release rates are strongly dependent upon the pH of the medium and the temperature.     

微球-三维支架复合体系控制释放生长因子的研究进展

将载生长因子的微球和组织工程三维支架复合得到的微球-三维支架复合体系,能够实现多种生长因子的依次释放和连续释放,满足新组织形成过程中不同阶段对不同量的各种生长因子的需求。在综述了微球和支架作为载体的载生长因子方法及优缺点的基础上,评述了微球-三维支架复合体系的三种制备方法,即自上而下法、复合溶结法和直接混和法,归纳和总结了国内外对微球-三维支架复合体系的研究现状和进展。并阐述了微球-三维支架复合体系的释放机理,指出了微球-三维支架复合体系在理想组织修复中的发展潜力和面临的挑战。