壳聚糖ppt
关于壳聚糖的溶解性以及应用PPT讲稿
糖可用作基因转移工具。
• 3.1 在医药领域的应用
• 壳聚糖可以用来制备伤口覆盖膜，具有很
好的生物相容性和抗病毒性，并能促进创 面的愈合。例如，用壳聚糖制成的口腔溃 疡膜，疗效可靠，无不良反应。
• 壳聚糖及衍生物在人体内可生物降解，并
相类似，分子呈直链状，极性强，易结晶，但由于熔点高于其自身分 解温度，故不易得到非晶态的壳聚糖。
• 在特定的条件下，壳聚糖能发生水解、烷
基化、酰基化、羧甲基化、磺化、硝化、 卤化、氧化、还原、缩合和络合等化学反 应，可生成各种具有不同性能的壳聚糖衍 生物，从而扩大了壳聚糖的应用范围。
• 其结构为下图所示：
• 自1859年，法国人Rouget首先得到壳聚糖
后，这种天然高分子的生物官能性和相容 性、血液相容性、安全性、微生物降解性 等优良性能被各行各业广泛关注，在医药、
• 3.3 在生化领域的应用
• 壳 聚糖具有生物降解的特性，可制成可降解的薄膜。壳聚糖的游离氨
基，对各种蛋白质的亲和力非常高，可用来作为固定化酶、抗原、抗 体等的载体。改性甲壳素固定化酶不影响酶的活性，且有很高的催化 能力，可重复使用。
• 壳聚糖的外观是白色或淡黄色半透明状固体，但壳聚糖不溶于水和碱
溶液，也不溶于硫酸和磷酸。溶于质量分数为1%的乙酸溶液后形成 透明豁稠的壳聚糖胶体溶液是最重பைடு நூலகம்的性质之一。
• 壳聚糖无毒、无害，具有良好的保湿性、润湿性，但吸湿性较强，遇
水易分解。其吸湿性仅次于甘油，优于山梨醇和聚乙二醇。
• 壳聚糖的相对分子质量为10万到30万之间。壳聚糖分子结构与纤维素
• 方法：将壳聚糖用高温浓碱浸泡，然后洗
壳聚糖ppt课件
四 壳聚糖抑菌性能影响因素、机 理及应用
1 壳聚糖的抑菌性能影响因素
（1） 分子量对壳聚糖抑菌性能的影响：
壳聚糖分子量对其抑菌性能的影响初步认为与不同 分子量壳聚糖的不同作用机理及细菌的不同结构与特性有关。
（2）浓度对壳聚糖抑菌活性的影响：
水溶性壳聚糖的抗菌活性随其浓度的增加而增加， 且它的抗真菌活性强于抗细菌活性。
2019 9
3 水溶性甲壳素的热性质
水溶性甲壳素的玻璃化转变温度( Tg)是 219．6℃。而脱乙酰度为95．8l％的壳聚糖的玻璃 化温度是202.6℃。水溶性甲壳素的玻璃化转变温 度高于壳聚糖，主要是因为水溶性甲壳素含有较多 的乙酰基，分子间的作用较壳聚糖强，分子运动更 困难。从水溶性甲壳素和壳聚糖的热失重结果分析， 二者在60℃附近开始脱水，水溶性壳聚糖脱去总重 的4.61％，而壳聚糖脱去了3.69％，说明水溶性甲 壳素的亲水性更好，在环境条件下样品含水量高， 与水的作用更强。
（3）壳聚糖在农业中的应用
可做种子处理剂、生物农药
2019 17
（4）壳聚糖在医疗卫生中的应用
壳聚糖可用于伤口填料物质，具有杀菌、促进伤口 愈合、吸收伤口渗出物、不易脱水收缩，减少疤痕的生 成等作用。
（5）壳聚糖在环保中的应用
利用壳聚糖的抗菌性，可将壳聚糖用于生化水处理 方面。
（6）壳聚糖在化妆品中的应用
2019
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6 金福生-壳聚糖抗菌成膜喷雾剂
简介：今福生是一种喷雾型分子级隐形敷料，喷洒在皮
肤、黏膜患处及损伤表面，通过全新的物理及生物双重抗 菌机制，隔离、杀灭病原微生物，同时促进组织修复与再 生。 作用机理：物理及生物双重抗菌机理。 使用范围：普通外科、皮肤科、妇产科、烧伤科、整形 美容外科、肛肠科、褥疮的预防与治疗、预防医院内感染 等。
关于壳聚糖的溶解性以及应用PPT课件
第十一页，共17页。
➢ .3.2 在环保领域的应用
➢ 由于游离氨基的存在，壳聚糖类在酸性溶液中具有阳离子型聚电介质的性质， 因此可作为凝聚剂用于水的澄清。还可用于工业废水的脱氯酚和造纸污水脱木 质素处理等。
➢ 壳聚糖是高性能的重金属离子捕集剂，因此可用于含重金属离子的污水处理 和贵金属的回收。将壳聚糖用于溶液中Cu2十、Cr3十 、Ni'+金属离子的脱 除和回收，最高回收率达95%一100%。例如，壳聚糖可速有效地吸附含Cr 废水中的Cr， 除Cr率达90%以上。用D-半乳糖改性的壳聚糖能吸附 Ga,In,Nd,Eu,Cu,Ni,Co等金属离子，壳聚糖分子的氨基和经基起了鳌合配位 体的作用。壳聚糖类也能用于放射性元素铀的捕集和核工业污水的处理。
第七页，共17页。
➢ 2.4外界环境Ｔ改变溶解性 ➢ 温度升高，分子(离子)的热运动加剧，使得分子间混台加快， 壳聚糖的溶解性
能同样能受到温度的影响。 ➢ 原理：由于升高温度之后，氢离子的运动速率加快，使得氢离子对氨基和羟基
作用加强同时大分子链运动加快，从而加快了壳聚糖有序结构的破坏，促进了 壳聚糖的溶解。 ➢ 但是升高温度对壳聚糖溶液也带来了不利的影响。由于壳聚糖的缩醛键结构， 在氢离子的攻击下很容易发生水解，使壳聚糖降解。当温度升高时壳聚糖降解 更为严重，所以溶解壳聚糖温度不宜过高，一般２０～３０度为宜，对于必须 加热的才能溶解的溶剂，也要尽量采取最低温度下使其溶解。
羧甲基壳聚糖 ppt课件
3.1高黏度壳聚糖
高黏度壳聚糖制备注意的环节： ➢ 虾蟹壳比蚕蛹壳、柠檬酸发酵菌渣等其他原料较有可
能制备出高黏度壳聚糖 ➢ 虾蟹壳堆放长时间后因微生物破坏，不能用于生产高
黏度壳聚糖。 ➢ 生产甲壳素的过程中，不能用浓度大的强酸、强碱高
温长时间处理。 ➢ 在生产壳聚糖过程中，要掌握高温、短时间原则。 ➢ 不能使用KMnO4等强氧化剂长时间脱色，强氧化剂对
生长链的部分水解，即糖苷键的断裂，形成许 多分子量大小不等的片段。 氧化法：过氧化氢氧化法最为常见，加入H2O2 进行降解反应。 酶解法：利用专一性或非专一性酶对甲壳素或 壳聚糖进行降解。
壳聚糖的应用
功能材料 医药卫生方面的应用 食品工业中的应用 农业中的应用 轻纺工业中的应用 在水处理中的应用
1.4 壳聚糖的化学性质
氧化
甲壳素和壳聚糖可以被氧化剂氧化。 氧化剂不同，反应的pH不同，机理和产 物也不同，既可使C6-OH氧化成醛基或羧基， 也可使C3-OH氧化成羰基（成酮），还可能 发生部分脱氨基或脱乙酰氨基，甚至破坏吡 喃环及糖苷键。
1.4 壳聚糖的化学性质
螯合
甲壳素和壳聚糖的糖残基在C2上有一个乙 酰氨基或氨基，在C3上有一个羟基，它们都是 平伏键，这种特殊结构使得它们对具有一定离 子半径的一些金属离子在一定的pH条件下具有 螯合作用，尤其是壳聚糖。
4.功能材料方面的应用
液晶 由于壳聚糖分子链上有氨基和羟基，可
进行各种化学修饰，从而可提供比纤维素液 晶更多的液晶理论知识和开发出更多的液晶 材料。
4.功能材料方面的应用
催化剂 壳聚糖的一些衍生物具有催化作用。 ✓ 有机金属配合物催化剂具有较高的催化活性
和选择性。 ✓ 人工模拟酶的研究。具有光学活性的特殊高
壳聚糖、甲壳素应用PPT课件
涂依
戊二醛为交联剂， 以涂覆的方法制备了壳聚糖 /羧甲基壳聚糖双层复合 膜， 羧甲基壳聚糖的分子量不同， 研究对比不同分子量羧甲基壳聚糖 双层复合膜的创伤修复效果。实验结果表明: 制备的双层复合膜对创伤 都有一定的修复效果，但是羧甲基壳聚糖的分子量越小，创伤修复效 果越好
余丕军
通过观察胶原蛋白 － 壳聚糖( 80: 20) 复合纳米纤维膜修复 SD 大鼠背部全层皮
营养药物载体 针对壳聚糖微球作为药物载体的研究已经有很多，但其作为营养药物载体的研究则比较少。目前，
壳聚糖微球在营养物运送方面的研究主要是作为维生素载体。
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甲壳素生物质转化为高附加值化合物
随着全球石油、天然气等传统化石资源逐渐枯竭，人们正在努力寻求新的替代能源。生物质是 一种天然可再生资源，数量巨大，价格低廉，丰富的生物质资源有望成为未来获取燃料和高附加值 化学品的主要来源。新加坡国立大学的颜宁教授等提出了甲壳素生物质精炼的概念，同时指出甲壳 素生物质来源丰富，应该像纤维素生物质一样被充分利用，使其转化成为具有较高价值的化学品。
表面释放
壳聚糖微球 溶蚀释放
扩散释放
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壳聚糖微球在药物载体中的应用
普通药物载体 壳聚糖微球作为普通药物的载 体，能提高药 物稳定性，保持药物长期活性。目前已有多种药物可通
过壳聚糖微球缓释，如四环素、奈普生、阿司匹林等。药物经过壳聚糖微球负载后缓释作用十分明显， 释放时间与原药相比都显著地延长。
生物大分子药物载体 用 壳聚糖微球作为多肽、蛋白质类药物的载体，不仅可以保护药物免受消化道酶的破坏及ｐＨ值的
肤缺损创面的作用， 修复后14d 实验组创面已经基本对合; 而仅用油纱及干纱布
包扎并在创伤外缘打包固定的对照组创面对合不整齐， 创面较实验组大。证实
速易康壳聚糖敷料课件
能够管理不同程度的渗液量
保持适当的湿润环境
不粘连伤口 防菌 防水 允许氧气及水蒸气通透 自溶清创 减少更换频率
伤口愈合发展的历史
1、湿性愈合理论： 1962年伦敦大学的Winter博士首先用动物试验（猪）证实，湿性环境的伤口愈合速度 比干性愈合快一倍 1963年Hinman进行人体研究，证实湿性愈合的科学性 七十年代“湿性伤口愈合”观念逐渐被广泛接受 2、湿性愈合实践：
八十年代，诞生了第一代保湿性水胶体敷料
“速易康”壳聚糖敷料 与传统产品功能对比
“速易康”壳 聚糖敷料 特强 强 强 是 是 好 是
天然纱布 水凝胶敷料 藻酸盐敷料 银离子敷料 吸收渗液能 力 抑菌能力 一般 无 无 否 否 否 否 较弱 无 强 否 否 否 否 强 无 较强 否 是 否 否 较强 强 强 是 是 否 否
保持湿润能 力 促进组织修 复 止血止痛能 力
细胞生长的调节作用
壳聚糖对机体细胞生长的调节作用着重表现在两个方 面：促进作用和抑制作用。壳聚糖的细胞吸附作用，主要 是对红细胞和肿瘤的吸附作用，这直接与其止血、抗肿瘤 转移等生物功能有关。对机体细胞的激活作用是壳聚糖的 一个生物特性，这个特性是使其具有免疫调节、促进创面 愈合等作用的主要原因。
对凝血功能的调节作用
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抗菌抗感染
壳聚糖对金黄葡萄球菌、大肠杆菌、小肠结尖耶尔氏菌、 鼠伤害沙门氏菌和李斯特单核增生菌，均有较强的抑制作用。 中国纺织大学吴清基教授已成功地将壳聚糖制成无纺布、流延 膜、涂层纱布等多种医用敷料用于临床，其中壳聚糖与醋酸制 成的无纺布透气透水性能极佳，用于大面积烧伤烫伤，抗感染 和促进伤口愈合效果很好。
壳聚糖妇用抗菌栓敷料演示课件
性阴道炎的临床疗效及安全性，将产品（试验组）用于细菌性阴道 病和霉菌性阴道炎患者120例的临床治疗，疗程7天，观察壳聚糖妇 用抗菌栓（敷料）对细菌性阴道病和霉菌性阴道炎治疗效果及安全 性，结果显示壳聚糖妇用抗菌栓（敷料）治疗效果显著，对人体无 毒副作用，疗效明显好于对照组。
• 司诺药业拥有专业化的服务团队，提供高品质产品，并为客户提供优质的售后服务， 指导客户进行市场操作，提高推广效率。公司建立了“稳定的价格体系”、“完善的 市场管控体系”、“优质的后期服务体系”。实施独家代理制度，统一零售价格，并 为客户提供便捷的物流服务，签约后快递免费送货上门。司诺药业视客户为合作伙伴， 明确企业责任，愿做好客户的后勤保障，做好后勤服务才是企业发展的根本，只要是 对销售有利的，就是我们要做的。司诺药业真诚希望与广大代理商精英们精诚合作、 共创辉煌！
• 4、高脱乙酰度壳聚糖是天然阳离子高分子聚合物，具有吸附性、成膜性，进入女性阴 道后，在阴道和宫颈部位形成一层保护膜，抑制致病微生物，阻断病原菌代谢。
• 5、高脱乙酰度壳聚糖在人体溶菌酶的作用下降解为低聚糖和单糖，可被人体吸收利用， 低聚糖能促进阴道内乳酸杆菌等有益菌的生长，调整阴道菌群平衡，提高机体免疫力。
产品特点
• 1、抗菌活性高，有效治疗霉菌感染、细菌感染、真菌感染引起的阴道疾病； • 2、促进血液凝固，快速止血，改善重度阴道疾病和宫颈糜烂引起的出血症状； • 3、在人体溶菌酶的作用下降解为低聚糖和单糖，可被人体吸收利用，低聚糖能促进阴
道内乳酸杆菌等有益菌的生长，调整阴道菌群平衡，提高机体免疫力； • 4、具有吸附性、成膜性，能吸附分解阴道和宫颈内的有害分泌物，并在阴道和宫颈表
面形成保护膜，有隔离保护和修复作用； • 5、采用脂溶性基质，在阴道内可迅速溶解并发挥药效； • 6、阴道给药更科学，药物可直达病变部位，迅速止痒、止痛； • 7、大剂量、性价比高，1盒用6天，患者容易接受。
壳聚糖ppt
2 水溶性甲壳素的表征
甲壳素、水溶性甲壳素以及其它不同脱乙酰度样品 在波数1650cm-1 和1550c-m1 附近的吸收峰是酰胺I带 (C=O)和酰胺II带(N-H和C-N的组合)的吸收峰，而脱乙酰 度达到95.81％的壳聚糖在此处几乎没有吸收。水溶性 甲壳素的酰胺I带吸收在166-15cm ，脱乙酰度为58.1％ 的壳聚糖的吸收在166-10cm ，甲壳素的吸收在 -1 1627cm ，谱带依次向低频移动，说明形成酰胺键中 的羰基形成氢键依次增多，分子间作用逐渐增强。在 波数34-51 5cm 、19-101cm 和6-165cm 3处红外吸收是壳 聚糖的结晶敏感吸收，水溶性甲壳素在上述3处都无明 显的吸收峰，说明水溶性甲壳素结晶性较差，而其它 的有明显的红外吸收。水溶性甲壳素在1O℃处的衍射 峰弱，在2O℃附近的衍射峰宽，说明非晶漫散射峰较 弱。
2 壳聚糖的生产技术
1）脱乙酰化原理
壳聚糖是甲壳素N-脱乙酰基的产物，壳聚糖的制备过程，就 是酰胺的水解过程。
2）资源化法
资源法包括有很多种方法，比如综合生产法、蝇蛆壳、蚕蛹 壳等。综合生产法是利用虾、蟹壳资源化处理法。该项技术的 关键，一是将虾、蟹壳中的中的成分转化为有用之物；二是尽 量减少烧碱的消耗，在海边的生产厂家，尽量使用海水，减少 淡水的消耗。蝇蛆壳又称蛆皮，干蛆皮中含有30%～54.8%的 甲壳素。
（3）脱乙酰度对壳聚糖抑菌活性的影响：
随着壳聚糖脱乙酰度的增加，抑菌性能增强，氨基 是壳聚糖的消毒因子。
（4）pH 值对抑菌性能的影响：
随着pH 值的降低，壳聚糖分子所带正增加，导致 了抑菌活性的增加电荷。
（5）菌株本身的影响：
虽然壳聚糖的分子量、pH 值等因素都是壳聚糖抑菌 活性的极显著影响因素，但菌株本身的内因才是壳聚糖抑 菌活性大小的关键因素。壳聚糖对革兰氏阳性菌的抑制作 用比对革兰氏阴性菌强。细菌容易受到壳聚糖的抑制，酵 母菌次之，而壳聚糖对真菌的抑制作用则相对较弱。
《壳聚糖纤维介绍》课件
CONTENTS
目录
• 壳聚糖纤维简介 • 壳聚糖纤维的应用 • 壳聚糖纤维的生产工艺 • 壳聚糖纤维的市场前景 • 总结与展望
CHAPTER
01
壳聚糖纤维简介
什么是壳聚糖纤维
定义
制备方法
壳聚糖纤维是一种由甲壳素脱乙酰化 得到的天然高分子材料制成的纤维。
通常采用溶液纺丝或熔融纺丝的方法 制备壳聚糖纤维。
壳聚糖纤维具有较好的吸附性能，能 够有效地吸附水中的重金属离子、有 机物和色素等污染物，为水处理提供 了一种高效、环保的方法。
壳聚糖纤维在环保领域的应用具有可 持续性和可降解性，符合绿色环保的 理念。
纺织领域的应用
壳聚糖纤维在纺织领域的应用包括制 作功能性纺织品和智能纺织品等。
壳聚糖纤维还可以与其他纤维混纺， 制作出具有多种功能的纺织品，如防 水透气的户外服装、智能调温的保暖 内衣等。
CHAPTER
02
壳聚糖纤维的应用
医疗领域的应用
壳聚糖纤维在医疗领域的应用包括制作医疗敷料、止 血材料、药物载体等。
输标02入题
由于壳聚糖纤维具有抗菌、消炎、促进伤口愈合等特 性，因此被广泛应用于伤口护理和手术止血等方面。
01
03
壳聚糖纤维制成的医疗敷料和止血材料具有良好的透 气性、吸水性和生物相容性，能够提供良好的伤口愈
壳聚糖纤维具有良好的抗菌、防臭、 防霉等性能，可以用于制作内衣、袜 子、床单等贴身纺织品，提高穿着的 舒适度和卫生水平。
CHAPTER
03
壳聚糖纤维的生产工艺
壳聚糖的提取工艺
壳聚糖的提取
从虾蟹壳中提取甲壳素，经过脱乙酰基反应后得到壳聚糖。
提取条件控制
壳聚糖纤维PPT课件
1、壳聚糖的基本性质
壳聚糖，又称甲壳胺，是甲壳素的N-脱乙酰基的产物，是自然界中 的唯一多糖,广泛存在于虾、蟹、蛹及昆虫等动物外壳以及藻类、菌类的细 胞壁中。地球上每年甲壳素的生物合成量仅次于纤维素，达到数十亿吨。
由于原料及生产方法的差异，其相对分子质量从几万到几百万不等。 一般而言，N-乙酰基脱去55%以上就可以称之为壳聚糖，这种脱乙酰度的壳 聚糖能溶于1%乙酸或1%盐酸。
第5页/共29页
二、甲壳素和壳聚糖的制备技术
虾蟹壳
洗涤
晒干
脱钙
4%-6% HCl
洗涤 10% NaOH
甲壳素
洗涤、干燥
脱色
洗涤
脱蛋白
0.5% KMnO4 80OC,10% 草酸
图1 甲壳素的制备工艺流程
第6页/共29页
二、甲壳素和壳聚糖的制备技术
与国内相比，国外生产甲壳素的方法主要是以蟹壳为原料， 用2%NaOH溶液在70℃先提取蟹壳中的蛋白质，然后用过量的亚硫 酸除去甲壳中的钙以获得甲壳素。该方法主要在于回收再利用亚 硫酸，以降低成本。
第26页/共29页
六、结论
可以预见，在不久的将来，壳聚糖纤维的市场需求量将会明显的上升，从而带动 壳聚糖纤维生产技术的革新，最终形成生产→消费→生产的良性循环。而在这场革命中， 谁掌握了新的技术，谁将掌控整个行业领域。
第4页/共29页
二、甲壳素和壳聚糖的制备技术
1、甲壳素的提取
尽管许多甲壳类动物都含有甲壳素，但从虾、蟹壳中提取 更为方便。虾、蟹壳主要由三种物质构成：以碳酸钙为主的无机 盐、蛋白质和甲壳素。
从虾蟹壳中提取甲壳素的流程如下：先将虾蟹壳洗净、晒 干，加入4%-6%的盐酸，常温下浸泡24h，使其中的无机盐转化为 氯化钙而溶解分离，将脱钙后的甲壳用水洗涤干净后加入10%的 NaOH溶液中煮沸6h，以去除蛋白质得到甲壳素的粗产品。将甲壳 素粗产品加入到0.5%的KMnO4溶液中搅拌并浸泡1h后水洗至中性， 然后在800C ，10%的草酸溶液中搅拌1h，使其脱色，再水洗、干 燥得到较高纯度的甲壳素。
壳聚糖
Carbohydrate Polymers 117(2015)524–536Contents lists available at ScienceDirectCarbohydratePolymersj o u r n a l h o m e p a g e :w w w.e l s e v i e r.c o m /l o c a t e /c a r b p olReviewGlycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applicationsHui Yun Zhou a ,∗,Ling Juan Jiang a ,c ,Pei Pei Cao a ,Jun Bo Li a ,Xi Guang Chen b ,∗∗aChemical Engineering &Pharmaceutics College,Henan University of Science and Technology,263Kaiyuan Road,Luoyang,471023,PR China bCollege of Marine Life Science,Ocean University of China,5Yushan Road,Qingdao,266003,PR China cLiaoning Haisco Pharmaceutical Co.,Ltd.,PR Chinaa r t i c l ei n f oArticle history:Received 7May 2014Received in revised form 24September 2014Accepted 25September 2014Available online 19October 2014Chemical compounds studied in this article:Chitosan (PubChem CID:71853)␣-glycerophosphate (PubChem CID:14754)-glycerophosphate (PubChem CID:6101544)acetic acid (PubChem CID:176)lactic acid (PubChem CID:612)Keywords:Chitosan-Glycerophosphate ␣-Glycerophosphate Thermosensitive hydrogel Drug deliveryTissue engineeringa b s t r a c tChitosan is non-toxic,biocompatible and biodegradable polysaccharide composed of glucosamine and derived by deacetylation of chitin.Chitosan thermosensitive hydrogel has been developed to form a gel in situ,precluding the need for surgical implantation.In this review,the recent advances in chitosan ther-mosensitive hydrogels based on different glycerophosphate are summarized.The hydrogel is prepared with chitosan and -glycerophosphate or ␣-glycerophosphate which is liquid at room temperature and transits into gel as temperature increases.The gelation mechanism may involve multiple interactions between chitosan,glycerophosphate,and water.The solution behavior,rheological and physicochemical properties,and gelation process of the hydrogel are affected not only by the molecule weight,deacetyla-tion degree,and concentration of chitosan,but also by the kind and concentration of glycerophosphate.The properties and the three-dimensional networks of the hydrogel offer them wide applications in biomedical field including local drug delivery and tissue engineering.©2014Elsevier Ltd.All rights reserved.Contents 1.Introduction .........................................................................................................................................5252.Chitosan/-glycerophosphate hydrogels ...........................................................................................................5252.1.Development process and gelation mechanism ............................................................................................5252.2.Preparation and properties ..................................................................................................................5283.Chitosan/␣-glycerophosphate hydrogels .........................................................................................................5303.1.Development process and gelatinize mechanism...........................................................................................5303.2.Preparation and properties ..................................................................................................................5304.Biomedical applications of chitosan/glycerophosphate based hydrogels ..........................................................................5314.1.Local drug delivery ..........................................................................................................................5314.2.Tissue engineering applications .............................................................................................................5325.Conclusion ...........................................................................................................................................534Acknowledgments ..................................................................................................................................534References ...........................................................................................................................................534∗Corresponding author.Tel.:+86037964231914.∗∗Corresponding author.Tel.:+86053282032586;fax:+86053282032586.E-mail addresses:hyzhou@ (H.Y.Zhou),xgchen@ (X.G.Chen)./10.1016/j.carbpol.2014.09.0940144-8617/©2014Elsevier Ltd.All rights reserved.H.Y.Zhou et al./Carbohydrate Polymers117(2015)524–5365251.IntroductionHydrogels are composed of three-dimensional polymer networks that have a high number of hydrophilic groups.The hydrogels can absorb large quantities of water and will neither disintegrate nor dissolve.Fully swollen hydrogels are soft,pliable, and low interfacial tension with water or biologicalfluids.The high water content of hydrogel renders it compatible with most living tissue and the viscoelastic nature of hydrogel minimizes damage to the surrounding tissue when it is implanted in the host.These characteristics make hydrogel an ideal candidate in biomedical applications such as remedying injuries to living sys-tems(Bhattarai,Gunn,&Zhang,2010).In addition,hydrogels can serve as a supporting material for cells during tissue regeneration as well as drug delivery system because the hydrogel’s physico-chemical properties are similar to the native extracellular matrix both compositionally and mechanically(Lee&Mooney,2001; Tessmar&Gopferich,2007).The hydrogel will become responsive to environmental stimulation if the polymer network of hydrogel is endowed with functional groups(Buenger,Topuz,&Groll,2012). The stimulation may be temperature,pH,biomolecules,electric field,magneticfield,light rays and so on.When the environment stimulation is changed,the hydrogels undergo a volume-phase transition due to molecular interactions resulting in abrupt changes in the network such as swelling,collapse or sol-to-gel transition.Glycerophosphate is an organic compound naturally found in the body which is usually used as a source of phosphate in the treatment of unbalance of phosphate metabolism and its veinal administration has been approved by FDA.-Glycerophosphate has been shown as an osteogenic supplement when added to cultures of human bone marrow stem cells.␣-Glycerophosphate is the mixture of␣-glycerophosphate and-glycerophosphate,and␣-glycerophosphate has linear chain structure and shows less steric hindrance than-glycerophosphate.Glycerophosphate also has been used as a catalyst to cause a sol-to-gel transition in chitosan solutions at physiological pH and temperature.Chitosan,the cationic(1-4)-2-amino-2-deoxy--D-glucan, partly acetylated to the typical extent close to0.25is industrially produced in medical/pharmaceutical grade from marine chitin (Jayakumar,Menon,Manzoor,Nair,&Tamura,2010;Jayakumar, Prabaharan,Nair,&Tamura,2010;Jayakumar et al.,2010; Muzzarelli,2009;Muzzarelli,2010;Muzzarelli,2012;Muzzarelli et al.,2012).The development of chitosan hydrogel has been an area drawing intensive investigation and a large amount of works have been reported on chitosan hydrogel and its potential use in various applications(Lee et al.,2009;Nagahama et al.,2009;Sung et al.,2010;Tang,Du,Hu,Shi,&Kennedy,2007;Zhou et al.,2012).Chitosan hydrogels have been prepared with a variety of differ-ent geometries and formulations including liquid gels,beads,films, tablets,capsules,microspheres,microparticles,sponges,and textile fibers(Denkbas,2006;Hamidi,Azadi,&Rafiei,2008;Khan,Tare, Oreffo,&Bradley,2009;Ladet,David,&Domard,2008).In each preparation,the polymer binding is accomplished either by non-covalent physical association,such as secondary forces(hydrogen, ionic,or hydrophobic bonding)and physical entanglements,or by covalent cross-linked chemical association(Hoffman,2002).Physi-cal associated networks can often be obtained by simply mixing the components which make up the gel under the appropriate condi-tions.Furthermore,the gelation,requiring no toxic covalent linker molecules,is always safe for clinical applications.This review focuses on the hydrogel based on different glycerophosphate including the preparation and applications, which is a temperature-sensitive physical associated network. There are several excellent reviews of hydrogel or chitosan-based hydrogel(Bhattarai et al.,2010;Buenger et al.,2012; Hoffman,2002;Lee&Mooney,2001)and there is a review about thermosensitive chitosan/glycerophosphate-based hydrogel and its derivatives(Supper et al.,2014),but an in-depth review on chitosan/glycerophosphate hydrogel based on the different glyc-erophosphate cannot be found ever.In this review,we will summarize the various categories of chitosan/glycerophosphate hydrogels prepared with chitosan and-glycerophosphate or␣-glycerophosphate,describe the preparation methods,introduce the properties and gelation mechanism,and present recent advances in biomedical applications.2.Chitosan/-glycerophosphate hydrogels2.1.Development process and gelation mechanismChitosan dissolves in acidic environments via protonation of its amine groups.Once dissolved,chitosan remains in solution up to pH value in the vicinity of6.2.Neutralization of chitosan aqueous solutions to pH value exceeding6.2systematically leads to the for-mation of a hydrated gel-like precipitate.Effort on chitosan neutral solution isfirst proposed by Chenite et al.(2000).Theyfind that chi-tosan solutions remain liquid below room temperature,even with pH values within a physiologically acceptable neutral range from 6.8to7.2,in the presence of-glycerophosphate salt.The system becomes thermally sensitive,which is liquid at room temperature and solidifies into gel as temperature increasing to body tempera-ture(Fig.1)(Ruel-Gariépy et al.,2004).-glycerophosphate plays three essential roles in the system:(1)to increase the pH into the physiological range of7.0–7.4;(2)to prevent immediate precip-itation or gelation;and(3)to allow for controlled gel formation when an increase in temperature is imposed.The sol-to-gel tran-sition temperature is pH-sensitive and gelling time is shown to be temperature-dependent.The molecular mechanism of gelation may involve multiple interactions between chitosan,-glycerophosphate,and water (Crompton et al.,2005;Ruel-Gariépy,Chaput,Guirguis,&Leroux, 2000).The effective interactions responsible for the sol/gel tran-sition included:(1)the increase of chitosan interchain hydrogen bonding as a consequence of the reduction of electrostatic repulsion due to the basic action of the salt,(2)the chitosan-glycerol-phosphate electrostatic attractions via the ammonium and the phosphate groups,respectively,and(3)the chitosan–chitosan hydrophobic interactions which should be enhanced by the struc-turing action of glycerol on water.The solution behavior of chitosan/-glycerophosphate hydro-gel is affected by the concentration of chitosan and-glycerophosphate(Cho,Heuzey,Bégin,&Carreau,2006a).The pH of chitosan solution is slightly increased with increasing of -glycerophosphate concentration due to the neutralizing effect of the phosphate groups.The pH increase with polymer concen-tration is due to the consumption of H+ions in solution by the protonation of the free amine groups.The relationship between gelation temperature and concentration of chitosan(C C)and-glycerophosphate(C GP)is shown in Fig.2.The region below the surface is the sol state,while that above is a gel.T gel is gradually decreased with increasing of C GP and C C.However,a synergetic effect at high C GP and C C results in a sudden drop of the gelation temperature and a phase transition which is on the edge between concentration-induced and heat-induced gelation.The rheological and physicochemical properties of the chitosan/-glycerophosphate system in terms of temperature are investigated sequentially(Chenite,Buschmann,Wang,Chaput, &Kandani,2001;Cho,AndréBégin,&Carreau,2005).Increasing temperature has no effect on the pH value of the chitosan/-glycerophosphate system,while conductivity is increased.The results indicate that the decrease of potential ionic interactions526H.Y.Zhou et al./Carbohydrate Polymers 117(2015)524–536Fig.1.The CS/GP formulation at room temperature (left)and at 37◦C (right).Figure was reprinted from Ruel-Gariépy et al.(2004).such as ionic bridging is resulted in by the reduction of the ratio of NH 3+in chitosan and OPO(O −)2in -glycerophosphate at high temperature.On the other hand,the favorable conditions for gel formation resulted in by the increased ionic strength as a function of temperature involved which enhanced screening of electrostatic repulsion forces and hence more polymer–polymer hydrophobic interactions.Since it is generally assumed that hydrogen bonding interactions are not predominant at high temperature and hydrophobic effect is the main driving force for the chitosan/-glycerophosphate gelation at high temperature.To expand this standpoint,physicochemical and rheological properties of the chitosan/-glycerophosphate system is inves-tigated in the presence of urea,which is a hydrogen bonding disrupting agent and can also affect hydrophobic interaction (Cho,Heuzey,Bégin,&Carreau,2006b ).Heat-induced gelation of the chitosan system in the presence of urea shows higher gelation temperature in nonisothermal tests and longer gelation time in isothermal conditions.At low temperature,urea strongly affects polymer–polymer interactions by weakening hydrogen bonds.With temperature increasing,it hinders hydrophobic effect since the reduction of ionic strength results in less screening of elec-trostatic repulsion between protonated glucosamine groups.It is confirmed that hydrophobic effect is the main driving force for the chitosan/-glycerophosphate heat-induced gelation.Aliaghaie,Mirzadeh,Dashtimoghadam,and Taranejoo (2012)have investigated the gelation mechanism of injectable thermosen-sitive hydrogels comprising chitosan and -glycerophosphate by rheological measurements for a drug delivery.According totheFig.2.Phase diagram for T gel under various -GP (C GP )and chitosan (C C )concen-trations.Figure was reprinted from Cho et al.(2006a).gelation behavior,three regions are defined:(1)a liquid-like behav-ior at low temperature,(2)a fast gelation process near the gel point,and (3)a slow gelation process at higher temperatures (seen in Fig.3).The theory initially worked out by Fredrickson and Larson for block copolymers near their order–disorder transition is extended and proposed to precisely determine the gel point in such systems by considering the aggregation of hydrophobic acetylated blocks of chitosan chains and gelation in chitosan/glycerophosphate systems as an order–disorder transition of block copolymers.Upon heat-ing,the water sheaths around chitosan chains are removed and the heat induced transfer of protons from protonated amino groups to glycerophosphate occurs,and consequently the formation of hydrophobic interactions among chitosan chains is facilitated.Then the gelation process beyond the crossover point goes through a nucleation and growth mechanism and the growth of hydrophobic domains could happen through the reaction limited cluster aggre-gation.In the third region,the observed rheological behavior could be associated with the tendency of system to minimize its interfa-cial area through the Ostwald ripening process.In addition,the effect of molecular weight and deacetylation degree of chitosan on gelation process is researched.The results of the temperature sweep measurement (Aliaghaie,Mirzadeh,Dashtimoghadam,&Taranejoo,2012)have been shown that the G and G crossover point for lower molecular weight chitosan sample have been shifted to 33◦C,which is 2◦C higher than that for high molecular weight chitosan sample.This implies that the hydropho-bic interactions in lower molecular weight chitosan sample have been formed at a higher temperature,which might be a result of lower entanglement and shorter hydrophobic domains.Such an observation could be attributed to the lower molecular weight and consequently lower viscosity of the sample,which provides more possibility for aggregation and percolation of hydrophobic domains through reaction limited cluster aggregation theory.ItFig.3.The evolution of the storage (G )and loss (G )moduli of the chitosan hydrogel during heating from 25to 65◦C.Figure was reprinted from Aliaghaie et al.(2012).H.Y.Zhou et al./Carbohydrate Polymers117(2015)524–536527 Table1Parameters,gel temperature and gel time of chitosan/glycerophosphate hydrogels:some examples..Chitosan C GP(w/v)T gel/◦C Gel time ReferenceMw/kD DD C(w/v)-GP␣-GP700/200–30074%/99%1%(1/1)23%31–33120–280s Aliaghaie et al.(2012) 35091%1–2%0–8%32–4213–2min Chenite et al.(2001)552–80870–91%2% 5.6%37–66quickly Chenite et al.(2000) 85093%0.05–0.20M0.33–0.83M58–797–11s Cho et al.(2006a,b)140cps96.5%0.1512–0.1728%2–8%30.1–45.71–3min Dang et al.(2011)140cps96.5%0.1512–0.162%5–8%21–3530–90s Dang et al.(2012a,b)463–86281.8–83.4% 2.05%9.09%371400–2400s Douglas et al.(2013)455.295%2% 5.6%,7%33,37/Hastings et al.(2012)20–525cps91%2%8%374–10min Huang et al.(2009) 108086%2%8.33–9.09%25–3720–3min Ji et al.(2010)/95% 2.5%6–16%50–37Kempe et al.(2008) 31075% 1.5%0.045–1.155M3760–330s Kim et al.(2010)200–800cps75–80% 1.6%30%37/Kwon et al.(2012)/75–85%0.9% 5.8%376min Niranjan et al.(2013)/95% 1.4–2.2%w/w8–16%w/w37/Peng et al.(2013a,b)421.8/455.284%/95% 1.5%w/w7.27%w/w7.27%w/w375/140min Ruel-Gariépy et al.(2000) 113–90065–88%2%2–8%24.3–91.7/Tsai et al.(2011)300–40081.0–94.8% 1.8%5%372–60min Zan et al.(2006)5095%2%10%376min Zhang et al.(2013) 136075% 1.7–1.9% 2.5–7.5%3710min Zhou et al.(2009)88–136056.5–90.3% 1.0–3.0%5%3710min Zhou et al.(2008)-GP:-glycerophosphate;␣-GP:␣-glycerophosphate;T gel:gel temperature.could be suggested that the lower molecular weight has facilitated the aggregation and percolation of hydrophobic domains,which is consistent with the lower percolation temperature obtained from temperature sweep measurements.Furthermore,it is under-stood that the deacetylation of chitin chains to achieve chitosan preferably occurs at the amorphous zones,and hence blocktype distribution of hydrophobic and hydrophilic segments are the result.So deacetylation affects the gelation process by affecting the hydrophobic and hydrophilic properties of chitosan.Chitosan could be considered as a block copolymer of acetylated and deacetylated units and the thermo-gelation of the chitosan/glycerophosphate system happens due to aggregation of hydrophobic acetylated blocks,and could be considered as an order–disorder transition or phase separation.It is the same result as Ruel-Gariépy et al. (2000)that gelation could occur at relatively low temperatures depending on the deacetylation degree of chitosan.The increase in gelation rate observed with chitosans of higher deacetylation degree might be attributed to the increase in cross-link density between the phosphate groups of glycerophosphate and the ammo-nium groups of chitosan.The parameters,gel temperature and gel time of chitosan/glycerophosphate hydrogels from some ref-erences are shown in Table1.Tsai,Chang,Yu,Lin,and Tsai(2011)has explored the effect of nanosilver,chitosan characteristics,and solution conditions on gelation temperature of chitosan/-glycerophosphate thermosen-sitive hydrogel.The gelation temperature of hydrogel is decreased with the increasing of deacetylation degree of chitosan,concen-tration of-glycerophosphate,and pH value(6.5–6.8).It is also decreased with the decreasing of chitosan molecular weight.The present of12ppm nanosilver has no effect on gelation temperature. Then,effects of chitosan characteristics on the physicochemical properties are also studied by Chang,Lin,Tsai,and Tsai(2013). It is concluded that the gelation temperatures for the hydro-gels are measured in the range of32–37◦C by manipulating the molecular weight and deacetylation degree of chitosan and the glycerophosphate concentration.The structure of hydrogel with 88%deacetylation degree of chitosan is more porous,uniform,and connective than that of the hydrogel with80%deacetylation degree of chitosan.Li,Fan,Ma,et al.(2014)and Li,Fan,Zhu,and Ma(2014) have prepared the chitosan/-glycerophosphate hydrogel included human-like collagen and studied the gelation mechanism and its properties.The results show that an amide bond(CONH) is formed between the carbonyl(C O)of human-like collagen and the amino of chitosan and NRH2+is formed between the amide bond and-glycerophosphate.The temperature sensitivity depends on the hydrophobic–hydrophilic interaction of molecular chains,and the pH sensitivity depends on the electrostatic inter-action of ionic groups(NRH2+and OPO32−).In addition,the chitosan/human-like-collagen/-glycerophosphate hydrogel with crosslinking agent of carbodiimide is prepared and the proper-ties are also examined(Li et al.,2013).The results show that the gelation time,structure,equilibrium swelling and degradation in vitro and in vivo are dependent upon crosslinking and struc-ture of composite hydrogels.The hydrogel shows desirable gelling time,swelling ratio,smooth surface,regular porous networks and biodegradability.Furthermore,Li,Fan,Ma,et al.(2014) and Li,Fan,Zhu,et al.(2014)have prepared chitosan/human-like collagen/hyaluronic acid/-glycerophosphate hydrogels based on the self-assembly of chitosan/human-like collagen/hyaluronic acidfibers.The results indicate that a new amide bond (CONH)and NRH2+are formed.The gelling time and swelling behaviors are dependent on the intertwining,overlap and adsorp-tion of the polymer chains at various temperatures and pH values.Furthermore,the biological properties of the chitosan/-glycerophosphate system are investigated and the effects of different factors are analyzed.The effects of chitosan characteristics on the antibacterial activity,and cytotoxicity of chitosan/-glycerophosphate/nanosilver hydrogels are studied(Chang et al., 2013).It is concluded that the hydrogel could be prepared with lower molecular weight chitosan and lower concentration of nanosilver in order to reduce the cytotoxicity of nanosilver, while maintaining similar antibacterial activity with the hydro-gel prepared with higher concentration nanosilver and higher molecular weight chitosan.Then the effect of the self-assembly of chitosan/human-like collagen/hyaluronic acidfibers on the histo-compatibility of the hydrogels is studied(Li,Fan,Ma,et al.,2014; Li,Fan,Zhu,et al.,2014)and the result reveals that thefibers inside the hydrogel pores reduce the quantity of macrophages,decrease the degree of inflammation,and improve the anti-degradation of the modified hydrogels.528H.Y.Zhou et al./Carbohydrate Polymers117(2015)524–5362.2.Preparation and propertiesA novel injectable in situ gelling thermosensitive chitosan/-glycerophosphate formulation has been proposed in recent years (Chenite et al.,2000,2001;Ruel-Gariépy,Hildgen,Gupta,&Leroux, 2002).First,chitosan and-glycerophosphate solutions are pre-pared in deionized water.Second,the two solutions are chilled in an ice bath for15min.Then the-glycerophosphate solution is added dropwise to the chitosan solution under stirring and the resulting mixture is stirred for another10min.The release of macromolecules from the system could sustain over a period of sev-eral hours to a few days while the release of low-molecular-weight hydrophilic compounds is generally completely within24h.The gelation rate and gel strength is slightly increased by the adding of liposome to the chitosan/-glycerophosphate solution,and the liposome-chitosan/-glycerophosphate system rapidly gels at body temperature(Ruel-Gariépy et al.,2002).The similar prepara-tive method has been used to control the release of different model compounds(Ruel-Gariépy et al.,2000).Ruel-Gariepy et al.(2004) have proposed to use the chitosan thermosensitive hydrogel for the sustained release of paclitaxel at tumor resection sites in order to prevent local tumor recurrence.The macro-and microstructure of chitosan/-glycerophosphate systems is exosyndromed by rheology and electron paramagnetic resonance spectroscopy(Kempe et al.,2008).Increasing-glycerophosphate concentration leads to a lowering of the gelation temperature from about50◦C to37◦C,and higher-glycerophosphate concentrations lead to faster gelation.The results indicate that the insulin is incorporated into the aqueous environ-ment of the gel and released in its native form.The viscosity of the gelled system is much higher compared to the sol systems of the same composition.The pH of chitosan/-glycerophosphate solu-tion is between6.6and6.8which do not change during gelation irrespective of the proportion of-glycerophosphate.The gela-tion formation process does not change the microacidity inside the sample.Sharma,Italia,Sonaje,Tikoo,and Ravi Kumar(2007)have devel-oped a chitosan-based in situ gelling system for subcutaneous administration of ellagic acid.The ellagic acid/chitosan/-glycerophosphate hydrogel system shows an initial burst release in vitro with about85%drug releasing in12h followed by a steady release till160h.The data indicate that formulations are effec-tive against cyclosporine induced nephrotoxicity,where the ellagic acid/chitosan/-glycerophosphate hydrogel shows activity at10 times lower dose compared to orally given ellagic acid.So the bioavailability of ellagic acid can be improved by subcutaneous formulations administered as simple ellagic acid hydrogel.Kim et al.(2010)have reported a thermosensitive chitosan hydrogel for the delivery of ellagic acid for the treatment of brain cancer. The gelation temperature and time are affected by thefinal pH of the chitosan/-glycerophosphate solution.Dialyzed chitosan solu-tion withfinal pH6.3greatly reduces-glycerophosphate needed for gelation,thereby significantly improves the biocompatibility of gel.The chitosan gels containing1%(w/v)of ellagic acid signifi-cantly reduces viability of U87cells and C6cells compared with the chitosan gels at3days incubation.Cui et al.(2011)have fabricated bioabsorbable chitosan/-glycerophosphate composite membranes through a relatively pH neutral and mild sol-to-gel process for guided bone regeneration. The results show that the chitosan/-glycerophosphate compos-ite membranes have a porous structure both at the surface and in sub-layers and the incorporation of-glycerophosphate in the chitosan matrix decreases the initial tensile strength of the mem-brane.The concentration of-glycerophosphate is proportional to the pore size and thickness but is inversely proportional to the tensile strength of the chitosan/-glycerophosphate membrane.Hydrogel beads are proposed with two sequential gelation steps based on chitosan/-glycerophosphate system and the model drug/cell(dexamethasone and L929cells)are immobilized inside (Lima,Correia,Oliveira,&Mano,2014).Superhydrophobic surfaces are used to produce the spherical hydrogel particles that provided favorable conditions to encapsulate cells or bioactive agents.First, the chitosan acidic solution is neutralized with-glycerophosphate at room temperature to pH6.2.Suspended cells(or dexametha-sone)in the formulation are dispensed in controlled volumes onto biomimetic polystyrene superhydrophobic surfaces,to form spher-ical shapes.The addition of sodium tripolyphosphate on the top of each sphere induces an ionic gelation process of the chitosan through electrostatic interactions.At37◦C,the hydrophobicity of the chitosan/-glycerophosphate system increases and a second gelation step occurs,which increase the elastic modulus.The soft-ness andflexibility of the system can potentially be utilized to implant cells and therapeutic molecules using less invasive pro-cedures.Recent studies have been reported that the physical proper-ties includingflexibility and mechanical properties of CS/-GP hydrogel can be improved by blending chitosan with other mate-rials.Ngoenkam,Faikrua,Yasothornsrikul,and Viyoch(2010)have developed a thermosensitive hydrogel which forms gel rapidly by blending chitosan/-glycerophosphate solution with the pregela-tinized starch.The presence of starch in the system could increase the water absorption and average pore size of the hydrogels.The hydrogel could degrade in lysozyme slowly during56days of incubation.In vivo studies indicate that the hydrogel shows rapid formation and localization at the injection site(shown as Fig.4)and has a potential to stabilize chondrocytes which is characterized by the expression of type II collagen mRNA and protein.Sun,Jiang, Wang,and Ding(2012)have reported that hydrophilic polymer poly(vinyl alcohol)is blended into the thermosensitive hydro-gel composed of chitosan and glycerophosphate to mitigate the body responses and promote the drug bioavailability.The results show that the presence of poly(vinyl alcohol)improves the sur-face hydrophilicity of the hydrogel and inhibits the cell attachment on the hydrogel,which alleviates the further cell infiltration and tissue integration in body.In addition,the presence of poly(vinyl alcohol)leads to the more rapid gel formation and more compact network,which resisted the dehydration and survived the hydrogel from cell division.These advantages benefit the controlled release and absorption of cyclosporine A,and contribute to the higher drug bioavailability.Fatimi et al.(2012)have developed the chitosan/-glycerophosphate hydrogel which is injectable,radiopaque and contains sodium tetradecyl sulfate,a well-known sclerosing agent,in order to combine bloodflow occlusion and endothelium ablation properties.The hydrogel is shown to exhibit rapid gelation and good mechanical properties,as well as sclerosing properties. The preliminary animal study shows that no endoleak is detected in any of the three aneurysms treated with chitosan/sodium tetrade-cyl sulfate/-glycerophosphate hydrogel at3months.Generally, the prepared hydrogels have great potential as embolizing and sclerosing agents for endovascular aneurysm repair and possibly other endovascular therapies.Then chitosan radiopaque hydrogels are prepared using chitosan,-glycerophosphate,iopamidol,and different sodium tetradecyl sulfate concentrations to investigate whether embolization with chitosan/-glycerophosphate hydro-gel with or without a sclerosant can induce chemical endothelial ablation and prevent endothelial recanalization in a rabbit model (Chabrot et al.,2012).It is concluded that the viscosity obtained with chitosan,-glycerophosphate,and3%sodium tetradecyl sulfate permits better control during injection and longer vascular occlusion.Thesefindings,combined with the intravascular neo-vascularization observed with the chitosan/-glycerophosphate。
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1 壳聚糖的性质
1）壳聚糖的物理性质
壳聚糖是白色无定形、半透明略有珍珠光泽的固体，分 子量由构成的材料而定。壳聚糖是一类新的天然高分子螯 合剂，而且无毒无副作用。不溶于水和碱溶液，可溶于烯 的盐酸、硝酸等无机酸和大多数有机酸，不溶于稀的硫酸、 磷酸。具有很好的吸附性、成模型和通透性、成纤性、吸 湿性和保湿性。壳聚糖是一种亲水性天然高分子，具有复 杂的所螺旋结构。结构属于二糖，壳聚糖是有氨基葡糖糖 缩合而成，其基本单位是氨基葡糖糖，其结构基元是壳二 糖，壳聚糖结晶度较高，因此具有很稳定的物理性质。结 晶性不同，稳定性也就不同。
3 水溶性甲壳素的热性质
水溶性甲壳素的玻璃化转变温度( Tg)是 219．6℃。而脱乙酰度为95．8l％的壳聚糖的玻璃 化温度是202.6℃。水溶性甲壳素的玻璃化转变温 度高于壳聚糖，主要是因为水溶性甲壳素含有较多 的乙酰基，分子间的作用较壳聚糖强，分子运动更 困难。从水溶性甲壳素和壳聚糖的热失重结果分析， 二者在60℃附近开始脱水，水溶性壳聚糖脱去总重 的4.61％，而壳聚糖脱去了3.69％，说明水溶性甲 壳素的亲水性更好，在环境条件下样品含水量高， 与水的作用更强。
将壳聚糖溶解于稀酸中，加人已醇、吡啶、乙 酸酐的混和溶液，使壳聚糖与乙酸酐在均相条件下 进行乙酰化反应，从而得到50％左右脱已酰度的水 溶性壳聚糖。
实验中的影响因素
经过多次实验可知：(1)在严格控制均相的条 件下，高脱乙酰度的壳聚糖与乙酸酐发生乙酰化 反应能够得到脱乙酰度50％左右的水溶性壳聚糖， 而且只有50％左右脱乙酰度的壳聚糖才溶于水， 大于60％或小于40％的壳聚糖只能溶胀，甚至不 溶于水；(2)由于壳聚糖的乙酰化反应相当迅速， 将乙酸酐、吡啶溶解于乙醇中再加人到反应容器 中与壳聚糖发生反应是控制均相的好方法；(3)壳 聚糖与乙酸酐的乙酰化反应是一个快速反应，反 应物的物质的量的比为1：2．2时，产品的脱乙酰 度接近50％，水溶性最好。
2 水溶性甲壳素的表征
甲壳素、水溶性甲壳素以及其它不同脱乙酰度样品 在波数1650cm-1和1550cm-1附近的吸收峰是酰胺I带(C=O) 和酰胺II带(N-H和C-N的组合)的吸收峰，而脱乙酰度达 到95.81％的壳聚糖在此处几乎没有吸收。水溶性甲壳 素的酰胺I带吸收在1665cm -1 ，脱乙酰度为58.1％的壳 聚糖的吸收在1660cm -1，甲壳素的吸收在1627cm -1 ， 谱带依次向低频移动，说明形成酰胺键中的羰基形成 氢键依次增多，分子间作用逐渐增强。在波数 3455cm-1 、1901cm-1和665cm-1 3处红外吸收是壳聚糖的 结晶敏感吸收，水溶性甲壳素在上述3处都无明显的吸 收峰，说明水溶性甲壳素结晶性较差，而其它的有明 显的红外吸收。水溶性甲壳素在1O℃处的衍射峰弱， 在2O℃附近的衍射峰宽，说明非晶漫散射峰较弱。
二 水溶性甲壳素及其膜的制备 与表征
甲壳素具有许多重要的生物学特性，如生物相 容性、生物降解性、止血活性和促进创伤愈合活性， 因此在生物医学领域可用于可吸收手术缝线、药物 载体、抗肿瘤制剂、止血剂和创伤敷料等。甲壳素 可溶于浓酸(如盐酸、硫酸、磷酸)和酰胺-氯化锂 体系。 甲壳素不溶于水和大多数普通有机溶剂， 从而使甲壳素的加工与应用受到很大限制。研究表 明，甲壳素的水溶性与其脱乙酰度密切相关，脱乙 酰度在50％左右时水溶性最好，脱乙酰度超过60％ 和低于40％时水溶性降低甚至完全不溶于水。
在制备水溶性甲壳素的过程中，控制反应在均 相条件下进行是非常重要的。 反应中，将壳聚糖和
乙酸酐溶解在稀乙酸溶液中，并加入少量的吡啶增 加溶解性，确保反应在均相条件下进行。在反应的 过程中，为了防止局部反应剧烈引起凝胶化现象， 应先将吡啶、乙酸酐先后溶解于乙醇溶液中．再加 入到反应容器中与壳聚糖进行反应。由于该反应是 在均相条件下进行的，壳聚糖乙酰化的位置是随机 的，因此破坏了甲壳素的结晶并减弱了甲壳素分子 内及分子间的氢键作用，使甲壳素具有一定的水溶 性。与甲壳素均相条件下脱乙酰制备水溶性甲壳素 的方法相比，该方法具有操作简单、成本低，适于 大规模生产等优点。
实验运用电子显微镜研究了壳聚糖作用前后菌 体超微结构的变化，并用生化分析仪测定了作用 前后菌液中2种酶的变化，认为壳聚糖首先改变细 菌细胞膜的通透性并损坏细胞壁，进而引起细菌 细胞内酶外泄，从而抑制细菌的生长或死亡。
3 壳聚糖抗菌性能应用
（1）壳聚糖在工业上的应用
主要的加工对象是一些容易附着、繁殖、传播微生物的 纺织品，如羊毛制品和蚕丝制品等蛋白质纤维，其脱落物与 人体汗液混合后，形成了细菌和霉菌生长繁殖的丰富养料， 致使制品极易受到虫蛀或霉变。
2 壳聚糖的生产技术
1）脱乙酰化原理
壳聚糖是甲壳素N-脱乙酰基的产物，壳聚糖的制备过程， 就是酰胺的水解过程。
2）资源化法
资源法包括有很多种方法，比如综合生产法、蝇蛆壳、蚕 蛹壳等。综合生产法是利用虾、蟹壳资源化处理法。该项技术 的关键，一是将虾、蟹壳中的中的成分转化为有用之物；二是 尽量减少烧碱的消耗，在海边的生产厂家，尽量使用海水，减 少淡水的消耗。蝇蛆壳又称蛆皮，干蛆皮中含有30%～54.8% 的甲壳素。
3）微生物法
微生物法是直接培养真菌制取甲壳素或直接提取壳聚糖， 分别有黑曲霉、丝状真菌、米根霉等。除上面的方法外还有微 波法等一些方法。
3 甲壳素/壳聚糖敷料
壳聚糖膜能止痛、止血、止痒，有效地促 进创面表皮重建和伤口愈合，减小瘢痕。壳聚糖 /甲壳素敷料可分为单纯的、复合的甲壳素/壳聚 糖敷料、还有甲壳素/壳聚糖载药敷料和甲壳素/ 壳聚糖衍生物敷料两种敷料。
（2）壳聚糖在食品工业中的应用
由于壳聚糖良好的生物安全性和生物功能性，在食品加 工业上可用作食品填充剂、食物保鲜剂、增稠剂、食品抗氧 化剂、果汁脱酸剂、果汁澄清剂、保水剂、稳定剂、脱色剂、 乳化剂、抗菌剂、食品防腐剂、香味增补剂和功能性甜味剂 等，且应用潜力非常大。
（3）壳聚糖在农业中的应用
可做种子处理剂、生物农药
一 甲壳素/壳聚糖医用敷料研究
甲壳素是一种新型的维生素。壳聚糖是一种有机 酸。甲壳素化学名为2-乙酰氨基-(1，4)--葡聚糖， 如果将每个糖基上的乙酰氨基（CO-NH-）换成羟基 （HO-），就成了维生素。如果将糖基上的N-乙酰基大 部分去掉的话，就是甲壳素的最为重要的衍生物壳聚 糖。它们属天然线性多糖类化合物天然高分子甲壳素 和壳聚糖具有良好的物化性质、生理活性、生物相容 性和生物可降解性，无有害降解物，具有止血和抑菌 消炎、减少创面渗出和促进创伤组织再生、修复、愈 合的作用，并且柔韧性、吸水性和透气性在各种敷料 材料中具有优势，十分适合于裸露、需要保护的创面 作用，可促进伤口愈合和组织修复再生。
（3）脱乙酰度对壳聚糖抑菌活性的影响：
随着壳聚糖脱乙酰度的增加，抑菌性能增强，氨基 是壳聚糖的消毒因子。
（4）pH 值对抑菌性能的影响：
随着pH 值的降低，壳聚糖分子所带正增加，导致 了抑菌活性的增加电荷。
（5）菌株本身的影响：
虽然壳聚糖的分子量、pH 值等因素都是壳聚糖抑 菌活性的极显著影响因素，但菌株本身的内因才是壳聚糖 抑菌活性大小的关键因素。壳聚糖对革兰氏阳性菌的抑制 作用比对革兰氏阴性菌强。细菌容易受到壳聚糖的抑制， 酵母菌次之，而壳聚糖对真菌的抑制作用则相对较弱。
五 壳聚糖膜性质的研究
高分子量的壳聚糖膜表面较为光滑，透光性较 好，透气性、渗透性和生物降解性较差；低分子量 的壳聚糖膜表面较为粗糙，透气性、渗透性和生物 降解性较好，但透光性较差。膜的结晶性和超微结 构决定了不同分子量壳聚糖膜具有不同的性质。壳 聚糖是天然生物多糖甲壳质的脱乙酰基衍生物，其 存在自由氨基，具有十分活泼的物理化学性质，由 于壳聚糖具有无毒副作用、良好的生物相容性、可 控的生物降解性、无抗原性等特性，又因为氨基性 质活泼，可用很多基团和化学物质进行修饰或连上 一些促进细胞生长的细胞因子和激素等物质，因此 壳聚糖及壳聚糖膜在生物医学、组织工程、药物缓 释、细胞及酶的固定化等许多方面的作用。
4 水溶性甲壳素膜的透汽性和吸水性
水溶性甲壳素的透汽性与壳聚糖相比有明显 的提高，这主要是因为水溶性甲壳素的亲水性比 壳聚糖好，使得水分子很容易与膜发生吸作用， 再通过水分子在膜内的渗透扩散，穿过水溶性甲 壳素膜。而甲壳素表现出较高的透汽性，主要是 因为甲壳素成膜时采用了氯化锂的二甲基乙酰胺 溶液作为溶剂，在氯化锂被水洗去的时候，在甲 壳素膜内形成了微孔结构，利于水分的通透。水 溶性甲壳素的溶解性较好，膜放入水中不长时间 就开始溶涨变形，最后被溶解。
4 液体敷料
液体敷料杀菌效果好、使用方便。其特征在 于：敷料所含的成分及其所占的重量比例为甲 壳素0.1-0.5%、杜米芬0.02-0.06%、胶元蛋白 0.5-1.5%。具有杀菌、消毒、止血、止痛、修 复创面的作用。
6 金福生-壳聚糖抗菌成膜喷雾剂
简介：今福生是一种喷雾型分子级隐形敷料，喷洒在皮
2） 壳聚糖的化学性质
甲壳素/壳聚糖与多种有机酸的衍生物如酸酐、酰卤等反 应。壳聚糖分子链上既有羟基，又有氨基，既在羟基上发生 酰化反应生成酯，也在氨基上发生，生成酰胺，分子结构中 有很多氨基，破坏部分氢键，使酰化反应容易发生，一般不 用催化剂，反应介质常用甲醇或乙醇。甲壳素/壳聚糖的羟 基与烃基化试剂反应生成醚，如甲基醚等。壳聚糖氨基是一 级氨基，有一对孤独电子有较强的亲核性，能发生许多反应， N-烷基化是除N-酰化外的另一类重要的反应。 壳聚糖与环 氧衍生物的加成反应，得到的是N-烷基化衍生物，该反应同 时引进了2个亲水性的羟基。壳聚糖在中性介质中很容易与 芳香醛（或酮）、脂肪醛反应生成西佛键。壳聚糖可被氧化， 氧化机理很复杂，氧化剂不同，反应pH值不同，反应产物 也随之而不同。
（4）壳聚糖在医疗卫生中的应用
壳聚糖可用于伤口填料物质，具有杀菌、促进伤口 愈合、吸收伤口渗出物、不易脱水收缩，减少疤痕的生 成等作用。
（5）壳聚糖在环保中的应用
利用壳聚糖的抗菌性，可将壳聚糖用于生化水处理 方面。