【作者】 赵育；

【导师】 陈国华；

【作者基本信息】 中国海洋大学 ， 海洋化学， 2004， 硕士

【摘要】 本文用氯乙醇作为醚化剂在碱性条件下与甲壳素进行醚化，合成了具有良好水溶性的羟乙基甲壳素（hydroxyethyl chitin,HECH）。由单因素实验确定了该醚化反应的主要影响因素，用正交实验的方法得出了HECH制备的最优条件为：碱含量15％，氯乙醇与甲壳素质量比为39：5，反应时间10小时，反应液固比（g：mL）为5：250，室温反应；对于醚化反应的收率影响因素最为重要的是氯乙醇用量，其次是液固比、碱含量和反应时间。用红外光谱和元素分析的方法对产品进行了结构表征。红外光谱的结果表明：经过醚化改性，3500cm^-1伯胺基伸缩振动小肩峰消失，与缔合羟基峰部分重合，证明部分游离氨基反应；3420cm^-1羟基吸收峰加强，出现羟基缔合的宽峰；元素分析的结果表明：HECH的取代度随着氯乙醇用量的增加而增加，基本上呈线性关系；当取代度大于1.619时，产物的水溶性较好；取代度小于1.619时，产物的水溶性不好。 用甲壳素与常用的吸湿保湿剂甘油、1，2丙二醇对比，对HECH的吸湿保湿性能进行了研究。结果表明：羟乙基甲壳素的吸湿性比甲壳素有较大的提高，在41％的相对湿度下，羟乙基甲壳素的吸湿率小于甘油和丙二醇约10％，保湿率与甘油和丙二醇相差不大；在81％的相对湿度下，羟乙基甲壳素的吸湿率比甘油和丙二醇低约40％，保湿率比甘油和丙二醇低约20％。 用NDJ-4旋转黏度计对HECH水溶液的流变性能进行了研究，发现HECH水溶液的黏度随浓度增加而增大，在2.0％浓度以上黏度急速增加，在质量浓度为1.0％-2.8％范围，为剪切变稀的假塑性流体，流动曲线符合幂律定律，利用多元线性回归方法对实验数据进行处理，获得恒定温度下稠度系数和非牛顿指数的经验关系式；在实验的温度范围25℃-45℃，不同质量浓度的流动活化能为4～16KJ／mol，求得了其黏流活化能与浓度经验关系式；HECH水溶液黏度在pH=7时最大，随着pH的增大或减小，黏度均下降；在2.5％的HECH水溶液中加入0.1～0.4mol/L的Na₂CO₃和Na₃PO₄时，其黏度值明显递增，随阴离子价数增高，影响增大；而加入0.1～0.4mol/L的NaCl和AlCl₃时，其黏度值逐渐减小，随阳离子价数增高，影响增大；用“剪切—静置法”研究了羟乙基甲壳素水溶液的触变性以及不同离子强度、pH值、不同表面活性剂，不同有机物对其触变性的影响，各流体均表现为正触变性。中国海洋大学硕二}一学位论文 分别用戊二醛、环氧氯丙烷、丙三醇三缩水甘油醚作为交联剂对HECH进行交联得到GA一HECH、ECH一HECH、PTGE一HECH三种以HECH为骨架材料的交联水凝胶，研究了交联反应的条件及产物的pH和温度的敏感性。结果表明:l、交联剂的种类对水凝胶的溶胀性和凝胶中的游离氨基含量有较大的影响，戊二醛交联水凝胶的游离氨基含量最小并且pH敏感性最差，另外两种水凝胶具有较好的pH敏感性;2、交联剂的用量越大，交联度就越高，凝胶的游离氨基含量就越少，同时一pH敏感性就越差。3、三种交联凝胶都属于pH敏感性凝胶，在pH6.98^pH3.O的缓冲溶液中的溶胀度大于pH10.08^pH6.98的缓冲溶液中的溶胀度。4、三种凝胶的溶胀度都随着温度的升高而增大，属于“热胀型”的凝胶。 用环氧氯丙烷活化法对ECH--HECH水凝胶进行了活化，并用正交实验考察了活化的最优条件，用乙二胺和己二胺对活化凝胶进行胺化，得到两种多胺基水凝胶。结果表明:胺化凝胶的溶胀度和pH敏感性与游离氨基含量和胺化剂的碳链长度有关，己二胺胺化的凝胶游离氨基含量大于乙二胺胺化凝胶，但己二胺的碳链比乙二胺长，溶胀度和敏感性比后者小。两种胺化凝胶都属于“热胀型”凝胶。 用化学交联法制备了由聚丙烯酸（P从）和llECH复合的互穿网络(Ip劝水凝胶。研究了交联剂含量、p从含量、pH和温度对于水凝胶的溶胀性能的影响。结果表明:该水凝胶在弱碱性（pH7.4，卜0.1）条件下的溶胀度远大于在酸性 （pHI .4，1二0.1）条件下的溶胀度，是一种PH敏感性水凝胶。随着温度的提高，凝胶的溶胀度也随着上升，该水凝胶也属于一种“热胀型”的水凝胶。 以GA一HECH和尸AA/HECH两种凝胶体系作为载体，分别包埋布洛芬和双氯芬酸钾两种药物，制成药物缓释制剂，体外释放实验结果表明:1、GA一HECH布洛芬体系第1h的累积释放率达到64%，前4h累积释放率达到82%，此后药物累积释放率基本不再增大。PAA/HECH布洛芬体系第lh的累积释放率达到28叹、，前4卜累积释放率达到81%。2、GA一HECH双氯芬酸钾体系第lh的累积释放率达到40%，药物在前6h累积释放率达到85%。PAA/HECH双氯芬酸钾体系第lh的累积释放率达到17%，12h内几乎是匀速释放，累积释放率达到扎%。因此，尸AA/HEC日比GA一HECH的药物缓释性能优异，体外释放效果良好，达到药物缓释制剂的要求。更多还原

【Abstract】 Chitin is the second most abundant natural polymer in the world . Hydroxyethyl chitin (HECH) is a water soluble chitin derivative which was prepared by etherification of chitin. Ethylene chlorohydrin was used as etherification reagent . Series of experiments were carried out on different amount of alkali and amount of chlorethyl alcohol, and different reaction time respectively. Monofactorial experiment and orthogonal design were used to acquire optimal values of experimental factors.The optimal combination of the reaction is as follows : alkalinity content (15%), reaction time (10 hours) , ethylene chlorohydrin: chitin (w/w)=39:5, the ratio of solid and liquid is 5g:250ml, room temperature . The structure of product was analyzed by infrared spectrum and elementary analysis. The IR spectra of chitin and HECH showed that there were marked difference between them: association hydroxyl peaks (3200cm~ 3500 cm ) were appeared in HECH which manifested strengthen of hydroxyl group .Amino-group (3450 cm) of chitin were disappeared in HECH ; The elemental analysis results showed that substituting degree increased with the increase of amount of ethylene chlorohydrin, which show linear relation .Hygroscopicity and humidity-retaining ability of chitin and HECH were studied by comparing to glycerine and propylene glycol . The results showed that hygroscopicity and humidity-retaining ability of HECH was better than chitin ,but not as good as glycerine and propylene glycol.The factors of influence on rheological property of HECH water solution were studied at different mass percentage (1%-2.8%) and different temperature (25 -45). The results show it was a pseudoplastic fluid. The flowing behaviour was coincided with power-law. As far as the experimental data were concerned, they were processed with regression method. Thus, the semi-experimental data fitting formulaunder certain temperature were gotten. The result of thixotropic experiment of series different HECH solution shows they are positive thixotropic liquid. Three novel hydrogels based on HECH was obtained by using glutaraldehyde(GA) epichlorohydrin (ECH) and PTGE as crosslinking reagents respectively. The swelling behaviour, swelling kinetics of HECH hydrogels and the effects of temperature , pH value on the swelling ratio of hydrogels were studied . The results showed that : (1) the swelling ratio of hydrogels decreased with the increase of dosage of crosslink reagents. (2) amount of liber amino-group of hydrogels was decreased with the increase of dosage of crosslink reagents. (3) The hydrogels exhibited a typical pH-sensitivity property .ECH-HECH hydrogel was activated by epoxy chloropropane on which ethanediamine and hexamethylendiamine were bonded as spacers. Orthogonal design was used to acquire optimal reaction conditions of activation. The amount of amino-group , swelling behaviour , swelling kinetics of hydrogels and the effects of temperature , pH value on the swelling ratio of hydrogel were studied . The results showed that ammates hydrogels had better pH sensitivity than former hydrogels .A series of interpenetrating polymer network hydrogels composed of different amount of PAA and HECH was prepared. The IR spectra and scanning electron microscope of HECH, PAA and IPN hydrogels confirmed that PAA and HECH was formed through chemical bond interaction. The IPN hydrogel exhibited a typical pH-sensitivity. The swelling ratio of hydrogels increased with the increase of temperature in artificial intestinal juice.The sustained-release drug systems of dichlofenac potassium and ibuprofen based on PAA/HECH IPN were prepared . The release experiments showed perfect release behaviors in artificial intestinal juice, especially for dichlofenac potassium sustained-release drug systems . This IPN system was expected to be used as a good drug delivery system for enteric medicine .更多还原