肝脂清胶囊的研制及其复方药代动力学的研究

【作者】 赵晓霞；

【导师】 颜正华； 龙致贤；

【作者基本信息】 北京中医药大学 ， 中药学， 2003， 博士

【摘要】 目的：研制一种治疗脂肪肝的中药新药----肝脂清胶囊。比较复方及姜黄色素粗提取物在动物体内的药代动力学参数，以探讨中药复方应用的合理性。方法：通过中医学理论和药效学实验初步筛选处方；根据文献资料和预实验确定处方中各味药的提取分离工艺，通过正交实验和单因素考察确定各味药有效部位最佳提取分离条件；以高效液相法和分光光度法确定四味药五个提取物的质量标准，并以薄层层析法和高效液相法制定成品的质量标准；通过初步稳定性实验，考察制剂的稳定性；通过有效成分姜黄素在大鼠和家兔体内的血药浓度测定，模拟药物动力学模型，比较姜黄色素提取物和制剂药代动力学参数，以比较复方和单味药应用的差别，探讨复方应用的合理性。结果：确定最佳处方为四味药的处方；工艺为泽泻70%乙醇提取，乙酸乙酯萃取；黄芩水提取酸沉淀；姜黄提取挥发油并以β-环糊精包结，药渣以乙醇提取，加硅藻土分散后以丙酮提取姜黄色素；柴胡醇提水沉，上AB-8大孔树脂柱，洗脱物再上氧化铝柱净化。五个有效部位混合，制粒，装胶囊即得成品。成品有效成分含量控制的指标为：每粒胶囊含姜黄素不得低于20mg。三个月初步稳定性实验研究表明，肝脂清胶囊在放置的三个月内质量稳定；药代动力学实验表明，肝脂清胶囊中姜黄素在体内的分布较慢而代谢的速度较姜黄提取物快，而且生物利用度较高，证实了复方用药较单独用药更为合理，可以提高生物利用度，同时避免药物在体内的蓄积。结论：肝脂清胶囊为工艺合理、质量稳定可控的中药新药；复方用药可提高生物利用度，避免药物在体内的蓄积。更多还原

【Abstract】 Objective To research and develop a new preparation of a compound of Chinese Medicine, Ganzhi Qing Capsule, which is effective on fatty liver， especially on NASH（nonalcoholic steatohapatitis）. To discuss the rationality of the compound Chinese medicine through contrast of pharmacokinetic experiments between preparation and single extract of curcuma.Methods Simplifying the compound Chinese medicine through the theory of TCM and pharmacological experiments; determining the preparing process of the effective parts of the four herbs; establishing the quality control methods of the five extracts and the preparation by TLC, HPLC and Spectrophotograph; examining the stability of Ganzhi Qing Capsule through primary stability experiment; Simulating the pharmacokinetics models, calculating the pharmacokinetic parameters and giving the difference through determining the concentration of bioactive composition in rabbits’ and rats’ blood. Results The best preparing process is: 1) Alismatis extracted with 80% alcohol. After evaporation of the solvent, the residue was dissolved in water and extracted with ethyl acetate. The organic layer was separated and washed with aqueous sodium bicarbonate to remove acidic substances; the ethyl acetate layer thus obtained is Alismatis Alisols. 2) Scutellariae extracted with water and precipitated with Hydrochloric acid. The sediment was washed with water and alcohol. The residue is crude baicalin. 3) Curcuma distilled with water to extract the volatile oil. The crude drug left was extracted with 80% alcohol. And after evaporation of the solvent the residue was mixed with Kieselguhr and dried. Then the mixture extracted with Petroleum ether. After evaporation of the solvent the residue was crude curcumin. The volatile oil was enveloped with β-CD. 4) Bupleurum extracted with 70% alcohol (pH=8.0). After evaporation of the solvent the residue was dissolved in water and precipitated for 12hr below 4℃. The liquid was separated by macrospore resin AB-8. Elution with 70% alcohol followed by water gave a solution. The solution passed through a column to remove coloring material. After evaporation and dryness crude saikosaponin is obtained. The five ingredients were mixed, granulated, and divided into capsules. The content of Curcumin in one capsule should be no less than 20mg. Curcumin is the<WP=7>main composition that makes Ganzhi Qing Capsule reducing the blood-lipid. Distributing and eliminating rates of Curcumin in Ganzhi Qing Capsule are moderate, but absorbing degree of the crude curcumin is less than that of preparation.Conclusion Ganzhi Qing Capsule is a new preparation with rationable technology and stable quality.更多还原