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·592· 精细化工 FINE CHEMICALS 第 38 卷

结果显示，随着加入 Ugi-Alg 载药微胶囊含量 [5] CAI X X, LIN Y F, OU G M, et al. Ectopic osteogenesis and
chondrogenesis of bone marrow stromal stem cells in alginate
的升高，其细胞活力逐步降低，说明过高浓度的 system[J]. Cell Biology International, 2007, 31(8): 776-783.
[6] POLYAK B, GERESH S, MARKS R S. Synthesis and characterization
Ugi-Alg 载药微胶囊，可能会妨碍细胞的正常生长。 of a biotin-alginate conjugate and its application in a biosensor
construction[J]. Biomacromolecules, 2004, 5(2):389-396.
但是培养 2 d 后，甚至在 Ugi-Alg 载药微胶囊质量浓 [7] HUANG R H, DU Y M, YANG J H. Preparation and in vitro
anticoagulant activities of alginate sulfate and its quaterized
度高达 400 mg/L 时，其细胞的存活率仍保持在 86% derivatives[J]. Carbohydrate Polymers, 2003, 52(1):19-24.
以上，说明 Ugi-Alg 载药微胶囊能够表现出良好的 [8] KANG H A, SHIN M S, YANG J W. Preparation and characterization
of hydrophobically modified alginate[J]. Polymer Bulletin, 2002,
细胞相容性。 47(5):429-435.
[9] FENG M X (冯美西), WANG Y F (王艳芳), CHEN X Q (陈秀琼),

et al. Synthesis and release properties of drug-loaded micro-/nano-
3 结论 micelles based on octyl alginate derivative[J]. Fine Chemicals (精细
化工), 2019, 36(9):1780-1786.
[10] YAN H Q, CHEN X Q, LI J C, et al. Synthesis of alginate derivative
via the Ugi reaction and its characterization[J]. Carbohydrate
针对前人 UGI 反应改性海藻酸盐的弊端，提出 Polymers, 2016, 136(10):757-763.
以对甲苯磺酰甲基异腈替代环己基异腈和正丙醛替 [11] UGI I. The α-addition of immonium ions and anions to isonitriles
accompanied by secondary reactions[J]. Angewandte Chemie
代甲醛的方法，通过 UGI 4 组分缩合反应制备了 DS International Edition in English, 1962, 1(1): 8-21.
[12] XU M H (徐明华). Asymmetric Ugi four-component reaction
分别为 19.41%和 14.12%的 Ugi-Alg-1 和 Ugi-Alg-2。 catalyzed by chiral phosphoric acid[J]. Chinese Science Bulletin (科
学通报), 2018,63(31): 3159-3160.
1
采用 FTIR 和 HNMR 表征改性产物（Ugi-Alg）的分 [13] PIRRUNG M C, SARMA K D. Multicomponent reactions are
accelerated in water[J]. Journal of the American Chemical Society,
子结构，验证了上述方法的可行性。TGA、XRD、 2004, 126(2): 444-445.
荧光光谱、SFT、TEM、激光粒度和 Zeta 电位分析 [14] BU H, KJONIKSEN A L, ELGSAETER A, et al. Interaction of
unmodified and hydrophobically modified alginate with sodium
对 Ugi-Alg 的性能测试结果表明，疏水侧基的接枝 dodecyl sulfate in dilute aqueous solution: Calorimetric, rheological,
and turbidity studies[J]. Colloids and Surfaces A: Physicochemical
破坏了原料 SA 的分子内氢键，使其微晶结构发生 and Engineering Aspects, 2006, 278(1/2/3): 166-174.
[15] BU H, KJONIKSEN A L, ELGSAETER A, et al. Rheological and
改变，热稳定性下降，分子链的灵活性增强。而且， structural properties of aqueous alginate during gelation via the Ugi
multicomponent condensation reaction[J]. Biomacromolecules, 2004,
Ugi-Alg-1 和 Ugi-Alg-2 的分子链可通过疏水缔合作 5(4): 1470-1479.
[16] BU H, KJONIKSEN A L, ELGSAETER A, et al. Effects of surfactant
用发生自由卷曲，形成胶束状的聚集体。Ugi-Alg-1 and temperature on rheological and structural properties of semidilute
和 Ugi-Alg-2 形成的胶束其 d H 分别为 659.4 和 aqueous solutions of unmodified and hydrophobically modified
alginate[J]. Langmuir, 2005, 21(24): 10923-10930.
534.6 nm，Zeta 电位分别为–54.6 和–60.8 mV，说明 [17] SUN Z X (孙竹兴). Design, synthesis and properties of antibacterial
polymer and sodium alginate drug-loaded gel by Ugi reaction[D].
在水溶液中 Ugi-Alg-2 分子间的疏水缔合作用更强， Baoding: Hebei University (河北大学), 2020.
[18] HUANG L Y (黄丽英), NIU X J (牛学军), SHI J C (史建纯). Research
并且 Ugi-Alg-1 和 Ugi-Alg-2 胶束可通过较强的静电 progress of formaldehyde inhibitor[J]. Chemical World (化学世界),
2013, 54(2): 125-128.
排斥力稳定分散于溶剂介质中，不易发生团聚。 [19] BULUT E. Ibuprofen microencapsulation within acrylamide-grafted
Ugi-Alg 载药微胶囊对布洛芬的释药性能分析结果 chitosan and methylcellulose interpenetrating polymer network
microspheres: Synthesis, characterization, and release studies[J].
表明，Ugi-Alg-1 和 Ugi-Alg-2 微胶囊的疏水内腔能 Artificial Cells, Nanomedicine, and Biotechnology, 2016, 44: 1098-
1108.
有效地增溶疏水性的布洛芬，迟滞药物的扩散，使 [20] BULUT E. In-vitro evaluation of ibuprofen-loaded microspheres
prepared from novel chitosan/poly(vinyl alcohol) interpenetrating
药物释放速率减慢。而且药物的释放过程符合 polymer network[J]. Journal of Macromolecular Science: Part
D-Reviews in Polymer Processing, 2014, 53(4): 371-378.
Non-Fickian 扩散机制，说明 Ugi-Alg 微胶囊溶胀降 [21] YAN H Q, CHEN X Q, FENG M X, et al. Entrapment of bacterial
解与其负载的药物扩散共同控制布洛芬药物的释放 cellulose nanocrystals stabilized Pickering emulsions droplets in
alginate beads for hydrophobic drug delivery[J]. Colloids and
速率。同时，Ugi-Alg 载药微胶囊的细胞毒性实验结 Surfaces B: Biointerfaces, 2019, 177: 112-120.
[22] CHEN X Q, YAN H Q, SUN W, et al. Synthesis of amphiphilic
果表明，Ugi-Alg 载药微胶囊能够表现出良好的细胞 alginate derivatives and electrospinning blend nanofibers: A novel
hydrophobic drug carrier[J]. Polymer Bulletin, 2015, 72(12): 3097-3117.
相容性。鉴于 Ugi-Alg 微胶囊对疏水性药物良好的 [23] LI X X, XU A H, XIE H G, et al. Preparation of low molecular
weight alginate by hydrogen peroxide depolymerization for tissue
负载和缓释性能，以及良好的细胞相容性，使其有 engineering[J]. Carbohydrate Polymers, 2010, 79(3): 660-664.
望应用于医药缓释制剂领域。 [24] YANG J S, REN H B, XIE Y J. Synthesis of amidic alginate
derivatives and their application in microencapsulation of λ-cyhalothrin[J].
Biomacromolecules, 2011, 12(8): 2982-2987.
参考文献： [25] QIN Z Y, JI L, YIN X Q, et al. Synthesis and characterization of
bacterial cellulose sulfates using a SO 3/pyridine complex in DMAc/
[1] LIU C L (刘长令), ZHAI Y Z (翟煜翥), ZHANG Y X (张运晓), LiCl[J]. Carbohydrate Polymers, 2014, 101: 947-953.
et al. Recent advance on fungicides for the control of botrytis [26] YAN H Q (颜慧琼), LI J C (李嘉诚), FENG Y H (冯玉红), et al.
cinerea[J]. Pesticides (农药), 2000, 39(3): 1-6. Stability and release properties of drug-loaded Pickering emulsions
[2] WANG D X (王德心). Application of TosMIC (tosylmethyl isocyanide) by the modified sodium alginate activated SiO 2 nanoparticles[J].
in organic synthesis[J]. Chemical Reagents (化学试剂), 1986, 8(4): Chemical Journal of Chinese Universities (高等学校化学学报),
34-44. 2013, 34(9): 2164-2170.
[3] WANG R, XU X P, MENG H, et al. 3-Phenacylideneoxindoles with [27] YANG L Q, ZHANG B F, WEN L Q, et al. Amphiphilic cholesteryl
tosylmethyl isocyanide and MeOH through C-C bond cleavage: grafted sodium alginate derivative: Synthesis and self-assembly in
Facile synthesis of pyrrole and 2H-pyrrolo[3, 4-c] quinoline aqueous solution[J]. Carbohydrate Polymers, 2007, 68(2): 218-225.
derivatives[J]. Tetrahedron, 2013, 69(6): 1761-1766. [28] RITGER P L, PEPPAS N A. A simple equation for description of
[4] LERTSUTTHIWONG P, NOOMUN K, JONGAROONNGAMSANG solute releaseⅠ. Fickian and non-fickian release from non-swellable
N, et al. Preparation of alginate nanocapsules containing turmeric oil[J]. devices in the form of slabs, spheres, cylinders or discs[J]. Journal of
Carbohydrate Polymers, 2008, 74(2): 209-214. Controlled Release, 1987, 5(1): 23-36.