基于胃内流体动力模拟的“药辅合一”多孔性白及胶胃内滞留行为及机制研究

“药辅合一”是中药制剂辅料的精妙运用。白及胶是中药白及止血、生肌之活性成分，兼具漂浮、粘附、膨胀及生物相容等特点，是理想的“药辅合一”胃部给药生物载体材料。人体胃具有复杂的生理结构加之胃排空运动，构成特殊的胃内流场环境，直接影响药物胃内运动状态，是胃内漂浮-生物粘附给药系统设计中的关键科学问题。本课题以多孔性白及胶为研究对象，基于胃蠕动的真实瞬时状态，使用计算流体力学领域FLUENT软件，采用已有研究的胃消化排空模型，模拟多孔性白及胶胃内运动轨迹，阐释其胃内滞留机理及其密度、黏度、分子量、降解性等对胃内滞留效果的影响规律；结合前期研究基础，以木香烃内酯为模型药，多孔性白及胶为载体材料，制备胃内漂浮-生物粘附协同型给药系统；评价其胃内滞留性能及抗胃溃疡药效，阐明多孔性白及胶作为 “药辅合一”胃滞留功能性辅料的机制和科学内涵，为基于计算机辅助设计的胃内滞留“精准药物”的研发提供新的研究思路。

Guiding ideal of “Unification of drug and adjuvant” is a wonderful application of adjuvant in traditional Chinese medicine(TCM) preparations. As a kind of active ingredient isolated from the Chinese medicine of Bletilla striata (Thunb.) Reichb.f. for hemostasia and myogenic, Bletilla striata polysaccharides gums(BSPG) has the capabilities of floating, adhesion, expansion and biocompatibility,and so on, which is the reason why BSPG may be used as a perfect drug carrier in the stomach under the guiding ideal of “Unification of drug and adjuvant”. At the same time, human stomach has complex physical structure and the phenomenon of gastric emptying movement, which leads to form the particular gastric fluid field, directly affects the dynamic state of drugs in stomach and becomes a critical scientific issues in the design of drug-delivery systems of intragastric floating-bioadhesive preparation. Therefore, in this proposal, we focus on the porous BSPG and according to the instantaneous state of gastric peristalsis, it is propose to use the computational fluid dynamics(CFD) software package FLUENT, adopt the previous model of gastric emptying during the gastric digestion and build gastric motion model to simulate movement process of BSPG in human stomach, explain the mechanisms on their gastric retention ability and investigate the influence of parameters on the gastric retention ability,such as density, viscosity, molecular weight and biodegradability, and so on. In addition, combined the base of the preliminary studies, costunolide as the tool medicine and the porous BSPG as the carrier, both will be choosed to apply in the preparation of intragastric floating-bioadhesive drug-delivery systems.Then the gastric retention capability and anti-gastric ulcers pharmacodynamics action of the complex will be evaluated. Moreover, BSPG,as the unification of drug and adjuvant as well as the functional auxiliary material of the intragastric floating-bioadhesive drug-delivery systems, whose mechanism and the scientific intension will be illustrated. Meanwhile, this study will provide a new idea for the development of gastroretentive dosage forms under the concept of “precision pharmacy” based on the computer-aided design (CAD) software.