水飞蓟宾+胆酸钠溶液的物理化学性质研究
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摘要
水飞蓟宾是水飞蓟素有效成分之一,水飞蓟素具有保肝药效。胆酸钠为消化液组分之一,对疏水性分子具有增溶作用。研究水飞蓟宾+胆酸钠体系的溶解、迁移和分子间相互作用,有助于了解消化液组分对疏水性药物分子性质的影响,为药物的控制释放技术提供参考数据。
     胆酸钠为双亲分子。胆酸钠不同于其它表面活性剂的重要特征之一是它没有固定的临界胶束浓度,而是一个逐步聚集的渐进过程。为研究其在溶液中的迁移性质,实验测定了胆酸钠溶液的体积、粘度和电导性质。在低浓度区间利用Ouint-Viallard方程求得胆酸根离子的无限稀释摩尔电导率,获得非聚集态的离子迁移特征参数。在胶束逐步形成的浓度区间,利用粘度和体积性质,结合Eyring的流体粘性过渡态模型,求得胆酸钠的迁移活化热力学函数。结果显示:其迁移活化热力学函数显著不同于非聚集态,具有聚集形成胶束的特征。
     实验测定了水飞蓟宾+胆酸钠溶液的UV-Vis光谱。考察水飞蓟宾浓度、胆酸钠浓度和溶液pH值对光谱的影响,从中获得水飞蓟宾与胆酸钠相互作用的信息。结果表明,水飞蓟宾在溶液中易发生质子迁移,溶液的pH值影响其酸式和碱式结构的平衡。胆酸钠不仅影响溶液的pH值,而且对水飞蓟宾的两种结构有不同的盐析盐溶效应。UV-vis光谱是酸碱平衡与盐析盐溶效应共同作用的结果。
     利用固液平衡法测定了水飞蓟宾在胆酸钠溶液中的溶解度。考察了温度、胆酸钠浓度对溶解度的影响。计算了水飞蓟宾溶解过程的热力学函数。结果显示:胆酸钠在形成胶束的浓度区间使水飞蓟宾的溶解度显著增大。
Silybin is an effective component of silymarin, which is a natural drug. Sodium cholate is one bile salt, which shows solubilization effect on the hydrophobic compounds. The aim of this work is to study the diffusion properties of sodium cholate, the molecular interaction between sodium cholate with silybin, and its effect on the silybin’s solubility. These studies are helpful to understand the influence of digestive liquid on the properties of hydrophobic drugs, and provide necessary reference data for controlled release of drugs.
     Sodium cholate is an amphiphilic molecular. One of its characteristics that different from ordinary surfactants is that the critical micelle concentration appears not as a definite concentration but over a certain concentration range. In order to study the diffusion properties of sodium cholate, density, viscosity and electrical conductivity of sodium cholate aqueous solution were measured experimentally. The molar conductance of cholate anion at infinite dilution was calculated by Quint-Viallard equation, which is a characteristic diffusion parameter of monomer ion. Furthermore, the activation thermodynamic parameters of viscous flow were calculated by Eyring’s transition state theory. Viscosity and volume properties were measured in the concentration region, where micelle is formed progressively. The result shows that the activation parameters of viscous flow is significant different from those of monomer. The UV-vis spectrum of silybin + sodium cholate aqueous solution was studied. The effect of pH values, the concentration of both silybin and sodium cholate on the UV-vis spectrum was consideried. Some information about the interaction between silybin and sodium cholate was obtained. Our result shows that, proton transfer process is toke place in silybin aqueous solution. The pH values show obvious effect on the equilibrium between silybin’s acid and bases structure. Sodium cholate has an important effect on the pH value, and therefore impacts the equilibrium between silybin’s acid and bases structure. Another effect of sodium cholate is the salting-in and out effect, which is different for silybins two structures. The UV-vis spectrum is the respons of two types effect.
     The solubility of silybin in sodium cholate aqueous solution was measured by a solid-liquid equilibrium method. The effect of temperature and concentration of sodium cholate was discussed. Thermodynamic functions were calculated for the dissolution process. Our result shows that, silybin’s solubility is enhanced largely in the concentration region, where sodium cholate forming micelle progressively.
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