生物相容性两亲分子溶致液晶的构筑及性能研究

【作者】 李振；

【导师】 王仲妮；

【作者基本信息】 山东师范大学 ， 物理化学， 2012， 硕士

【摘要】 生物相容性是指任何一种外源性物质，进入生物体或者与生物组织共存时，生物体自身容许这种外源性的物质在生物体内存留，包括生物体与这种外源性物质产生相互作用的能力和性质。而生物相容性的两亲分子，则指与生物体具有较好的相容性的两亲分子。以壳聚糖、烷基糖苷、葡糖酰胺、蔗糖酯、环糊精及其衍生物等为代表的生物相容性两亲分子，被食品和化学领域誉为世界级的新一代绿色无毒两亲分子，对人体几乎没有刺激，极为温和，还具有生物易降解的特性。生物相容性的两亲分子在应用方面的优越性主要表现在：(1)生物相容性两亲分子几乎没有毒性，对人体的眼睛以及皮肤极为温和，无不舒适的刺激感。促使这些生物相容性的两亲分子在药品和食品领域广泛使用，尤其是人们日常使用的化妆品和蔬菜水果洗涤剂中大幅增加使用。(2)生物相容性两亲分子与聚氧乙烯类表面活性剂相比易生物降解，且代谢物质有一定的营养价值。(3)生物相容性的两亲分子有非常理想的复配效果，几乎能与所有类型的表面活性剂复配使用。(4)部分生物相容性两亲分子具有药用价值，如壳聚糖可抗癌抑制癌细胞转移，蔗糖酯可降低血清中的胆固醇。选取绿色，易降解，对人体皮肤无刺激作用的生物相容性两亲分子，在适当条件下研究其聚集体性质，应用于基础药物的缓释和靶向释放，为实际的药物生产应用提供一定的理论指导。本文以硬脂酸蔗糖酯和水溶性壳聚糖为主要研究对象，通过表面活性剂之间的复配以及表面活性剂与生物相容性油相复配，研究环境温度、表面活性剂浓度以及复配对溶致液晶构筑和性能的影响。1.水溶性壳聚糖有序聚集体作VC载体的研究在水溶性壳聚糖水溶液中，通过改变表面活性剂的浓度和环境温度，研究有序聚集体的构筑与流变性能，结果表明：(1)流变数据表明，在全部的频率扫描范围内，有序聚集体Ⅱ比有序聚集体Ⅰ具有更大的储能模量和损耗模量。两种水溶性壳聚糖构筑的聚集体，都具有较强的假塑性，而且是良好的线性粘弹体，适合做药物载体。(2)缓释实验表明，水溶性壳聚糖的有序聚集体能够起到对维生素C的缓释作用。而且有序聚集体Ⅱ的内部网络结构比有序聚集体Ⅰ更加稳定，粘度更大，维生素C溶解过程更慢，从而能起到更好的缓释效果。(3)稳定性实验表明，两种水溶性壳聚糖的有序聚集体都对维生素C的稳定性具有很好的保护作用，以S3为例3小时维生素C的损失仅为0.92%，可以用作维生素C的抗氧化保护载体。2. S1570/ Brij98复配体系溶致液晶的构筑及性能研究在S1570/ Brij98复配体系中，通过改变表面活性剂的浓度和环境温度以及复配表面活性剂，研究有序聚集体的构筑与流变性能，结果表明：(1)第二种表面活性剂Brij98的引入，降低了S1570/水体系形成溶致液晶所需的最低温度，增加形成溶致液晶的表面活性剂质量浓度范围，扩大了溶致液晶区域。(2)油相分子IPM的引入，丰富了Brij98/S1570/water体系的溶致液晶相行为，当IPM含量增加时，降低了表面活性剂分子极性头基面积，增加了堆积参数(vL/aSlc)，诱导溶致液晶从层状结构向六角状液晶的转变。因此可以通过控制油相分子的浓度，可是实现对溶致液晶相行为的调控。(3)对于Bij98/S1570的质量比值为5/5的Brij98/S1570/IPM/水体系，油相IPM分子主要增溶在层状结构的栅栏层，随着IPM含量的增加，层状液晶的储能模量和临界应力值逐渐增加。对于Bij98/S1570的质量比值为3/7的Brij98/S1570/IPM/水体系，油相IPM分子主要增溶在层状结构的疏水内核，随着IPM含量的增加，导致层状液晶结构不断溶胀，体系中层状液晶样品宏观上的储能模量和临界应力值逐渐减小。3. S1570/Brij97复配体系溶致液晶的构筑及性能研究在S1570/Brij97复配体系中，通过改变表面活性剂的浓度和环境温度以及复配表面活性剂，研究有序聚集体的构筑与流变性能，结果表明：(1)通过DMF法合成的硬脂酸蔗糖酯在37oC时的CMC为1.902×10-4mol/L，γcmc=37.32 mN/m，并且未出现最低点。(2)在Brij98/S1570/水体系中，温度的升高和Brij97含量的增加有利于溶致液晶的构筑。BS1~BS4四个层状液晶的样品的稳态扫描都呈现剪切稀释行为，是假塑性流体。四个样品的频率扫描都表现为弹性体，符合层状液晶的典型特征。(3)在S1570和Brij97质量比分别为5/5和7/3的两个S1570/Brij97/油酸/水体系中，随着油相油酸含量的增加样品的偏光纹理由油纹变为十字花型纹理再到不完整的偏光纹理，频率扫描的储能模量和损耗模量逐渐减小，体系中的微观结构逐渐从层状液晶向胶束溶液转变。(4)由小角X射线的谱图，发现在S1570和Brij97质量比分别为7/3的S1570/Brij97/油酸/水体系中，油相油酸的影响更大。当油酸质量分数为20 %时，体系开始出现胶束相，溶致液晶结构开始破坏。而质量比分别为5/5的S1570/Brij97/油酸/水体系中，油相油酸的影响则较小，油酸含量为24 %时，体系的层状液晶结构仍然稳定存在。这说明当Brij97含量比较高时，体系的溶致液晶结构较为稳定，不容易破坏。更多还原

【Abstract】 Biocompatibility refers to a kind of property that when any foreign substancesenter into the biology or biological organization and coexist with noumenon, thebiology allows such substances exist in the body organisms and interact with thebiology. The biocompatible amphiphilic molecules is the surfactant has goodcompatibility with the biology. Chitosan, alkyl polyglucoside, glucose amide, sucroseester and cyclodextrins or its derivatives such representative biocompatibilityamphiphilic molecules are known as a new generation of world-class greenamphiphilic molecules and have the security non-toxic and mild to human body andeasily biodegradable properties. The superiority of biocompatibility mainly performsin several ways: （1） Biocompatibility amphiphilic molecules are almost non-toxic,have no stimulation to the eyes and skin. （2） Biocompatibility amphiphilic moleculesare more biodegradable than the kind of polyoxyethylene surfactants. （3）Biocompatibility amphiphilic molecules have a good effcet when it blends with othersurfactants. （4） Part of the biocompatibility amphiphilic molecules have a goodmedicinal value. Choose the green, easily degradable, no stimulus effect to humanskin biocompatibility amphiphilic molecules and study the aggregate properties ofsuch surfactants, then use it in the targeting release and slow-release of fundamentaldrugs, provide certain theoretical guidance for the actual drug production andapplication.In this paper, the sucrose ester and water-soluble chitosans are the main researchobjects, through mixing surfactants and blending surfactants with biocompatible oilphase to explore the influences of environmental temperature, surfactantconcentrations and interaction on the construction and performance of the liquidcrystal.1. Assembly of water-soluble chitosan used for VC carrierTwo kinds of ordered assemblies were found to be formed in the aqueoussolutions of a water-soluble chitosan, with changes in the concentration of the chitosan and temperature. （1） Steady rheological properties and dynamic rheologicalproperties of the two assemblies have been studied in different temperatures. Basedon this, choose two kinds of assemblies for release experiment of Vitamin C. （2）Steady rheological curves indicated that the two assemblies have strong fake plasticproperty. Dynamic measurements showed that the assemblyⅠmeets the Maxwellmodel in the low-frequencies, while it performs as an elastomer at the higherfrequencies. In the investigated frequency range, the loss modulus is always lowerthan the storage modulus for the assemblyⅡ. （3） Two kinds of assemblies have agood stability and release effect.2. Surfactant and oil effects on the liquid crystal formation ofS1570/Brij98 mixed systemsSurfactant and oil effects on the formation and the rheological properties oflyotropic liquid crystals formed by sucrose stearate were investigated by means ofphase diagrams, rheological techniques. （1） It shows that sucrose stearate can formliquid crystal phase at much lower concentration and lower temperature by addingoleyl polyoxyethylene （20） surfactant. After Inducing isopropyl myristate, the liquidcrystal phase formed by Brij98/S1570 system transformed from hexagonal liquidcrystal to lamellar liquid crystal. （2） The rheological experiments indicate that all theliquid crystal samples have strong fake plastic property and follow a shear-thinningbehavior. Dynamic measurements show that the hexagonal liquid crystal meets thegeneral Maxwell model, exhibiting viscoelastic behavior. In the investigatedfrequency range, the loss modulus of lamellar liquid crystal is always lower than thestorage modulus, performing as an elastomer. （3） In addition, when the mass ratio ofBrij98/S1570 is 5/5, shear stress and platform modulus of the lamellar liquid crystalincrease as the IPM concentration increases. Whereas at the 3/7 mass ratio ofBrij98/S1570, these values of lamellar liquid crystal decrease with this changes.3. Surfactant and oil effects on the liquid crystal formation ofS1570/Brij97 mixed systems In the S1570/Brij97 mixed systems, through mixing surfactants and blendingsurfactant with biocompatible oil phase to study the influences of environmentaltemperature, surfactant concentrations and interaction on the construction andperformance of the liquid crystal. （1） The sucrose ester is synthesized through theDMF method, its CMC is 1.902×10^-4mol/L and theγcmcis 37.32 mN/m. （2） Raisingtemperature or increasing the concentration of Brij97 help to form liquid crystal in theS1570/Brij97/H₂O mixed system. Steady rheological curves indicated that fourlamellar liquid crystal samples BS1^BS4 have strong fake plastic property. （3） In theS1570/Brij97/Oleic Acid/water systems at 37℃with the mass ratio of S1570/ Brij97is 7/3 and 5/5 respectively, polarizing texture of samples changes from oil texture intothe cross pattern texture and then changes to incomplete texture along with theincrease of the content of oleic acid. The storage modulus and loss modulus ofsamples reduce gradually as the oleic acid content increases, explaining that the layerstructure changes into micelle solution. （4） From the small Angle X-ray spectrumdiagram, we can find that Oil phase of oleic acid has much more influence on thestructure in the S1570/Brij97/Oleic Acid/water systems at 37℃with the mass ratio ofS1570/ Brij97 is 7/3. However, Oil phase of oleic acid has weak influence on thestructure in the S1570/Brij97/Oleic Acid/water systems at 37℃with the mass ratio ofS1570/ Brij97 is 5/5. When the content of Brij97 is higher, liquid crystal structure ismore stable in the mixed systems.更多还原