基于"谱效"关联的戊己胃内漂浮释药系统制备工艺环节评价研究

As a classic and famous prescription to treat gastric ulcer, Wu Ji Pellet has precisely clinical effects. Intra-gastric floating drug release system extends the residence time of this preparation in the stomach, thus increasing the drug's bioavailability. Since Wu Ji Pellet's anti-gastric ulcer pharmacodynamic material basis and composition mechanism are not yet clear, it's difficult to objectively evaluate the merits and demerits of preparation process of the intra-gastric floating drug release system. Based on Wu Ji Pellet's anti-gastric ulcer pharmacodynamic material basis, combining subjects like Modern Pharmaceutics, Instrumental Analysis, Mathematical statistics, Pharmacodynamics of TCM and so on, the study, by establishing a Spectrum Relationship Model between the in and ex vivo fingerprint data of Wu Ji Pellet's each disassembled prescription and its anti-gastric ulcer pharmacodynamic effects and conducting a comparative study, acquires fingerprint information closely related to Wu Ji Pellet's pharmacodynamic effects and then reveals Wu Ji Pellet's anti-gastric ulcer pharmacodynamic material basis and composition mechanism so as to specifically extract and separate its medicinal compositions, guide the preparation process of the intra-gastric floating drug release system. Moreover, the study dynamically reflects whether the medicinal compositions will degrade, covert or be reserved during the production process, objectively evaluates advantages and disadvantages of different crafts, sets up a new mode for evaluating preparation process of Wuji intra-gastric floating drug release system, guarantees its clinical effects, developing a new way to evaluate the preparation process of a new drug delivery system of Chinese herbal compound prescriptions.

课题组前期研究发现将戊己丸改制成戊己胃内漂浮释药系统可延长制剂在胃内滞留时间，提高制剂靶向治疗作用，但由于戊己丸抗胃溃疡药效物质基础及配伍作用机制尚未明确，无法从药效角度客观评价其胃内漂浮释药系统制备工艺环节的优劣，本课题拟从戊己丸抗胃溃疡药效物质基础研究出发，结合现代药剂学、仪器分析、数理统计学、中药药效学等学科，通过建立戊己丸及其拆方的体内、外指纹图谱信息与抗胃溃疡药效指标之间的谱效关系，获得与药效作用密切相关的体内、外指纹峰信息，并进行比较研究，进而揭示戊己丸抗胃溃疡药效物质基础及配伍作用机制，有针对性地进行药效成分的提取、精制，指导戊己胃内漂浮释药系统的制备工艺，动态反映药效组分在工艺过程中的降解、转化及保留与否，客观评价不同工艺的优劣，构建戊己胃内漂浮释药系统制备工艺环节评价的新模式，为中药复方新型给药系统制备工艺评价开辟了一条新途径。

项目背景： .课题组研究中发现戊己丸口服后，药物会随着胃的排空，很快进入小肠，不能较长时间在溃疡面形成有效的药物浓度，为进一步提高戊己丸疗效，诠释复方中药整体药效，制备基于中医药传统理论的中药新型给药系统，体现中医药整体观念、多靶点的药效特色，课题组提出建立戊己丸抗胃溃疡谱效关系数学模型，并以所确定的药效指标来优化戊己胃漂浮缓释系统的制备工艺这一新思路。.主要研究内容：.1.戊己丸物质基础研究：建立戊己丸及拆方指纹图谱及血清指纹图谱，进行戊己丸抗胃溃疡药效学试验，构建谱效关系模型。2.戊己胃内漂浮释药系统制备工艺研究：建立药效数据为评价指标的分析测定方法。3.戊己胃内漂浮释药系统评价：膨胀性、漂浮性、释放性。4.质量控制方法研究：含量、稳定性、有效期、重量差异、微生物限度等检查。.重要结果：.建立了戊己丸抗胃溃疡药效作用的谱效关系，构建新制剂戊己胃内漂浮释药系统制备工艺评价模式，项目后期建立了全方新型制剂的指纹图谱，严格控制最终产品质量。并结合体外漂浮性能、释药特性以及药效学的研究，对制剂进行全面评价，为中药复方新型给药系统制备工艺环节评价研究提供一条崭新的思路。.关键数据：.建立了戊己丸及拆方指纹及血清指纹图谱，并建立戊己丸“谱效关系”模型，谱效关联分析结果显示，戊己丸指纹图谱中峰面积与胃溃疡药效指标具有高度关联性，关联度均大于0.550。综合各因子权重系数对药效指标总贡献由大到小依次为：盐酸小檗碱＞芍药苷＞吴茱萸碱＞盐酸巴马汀＞吴茱萸内酯＞吴茱萸次碱＞黄连碱＞表小檗碱＞盐酸药根碱＞芍药内酯苷。.科学意义：.为进一步制备基于中医药传统理论的中药新型给药系统，体现中医药整体观念、多靶点的药效特色，课题组提出探索研究思路：首先，表征戊己丸复方药效物质基础；其次，建立谱效关系模型；最后，以所确定的药效指标优化新剂型戊己胃漂浮缓释系统的制备工艺，为今后中药新型给药系统的研发提供重要参考，具有科学指导意义。