Pre-clinical Pharmaceutical Research Of The New Drug Of ZXT Granule Of Zexie Decoction

Objective:To develop part pre-clinical pharmacy research on ZXT?Zexie Decoction?granules,which originated from the classical famous prescription Zexie Decoction,and lay a foundation for the development of new drugs for the treatment of phlegm-yin vertigo.Method:1.Screening categories of solvents for extraction of ZXT granules by metabolic cage of rat;2.Optimizing the preparation process of Zexie Decoction"standard decoction"and ZXT granule intermediates by central composite design-response surface methodology;3.Optimizing the formulation of ZXT granule by single-factor experiment;4.Establishing the quality standard of Zexie Decoction"standard decoction",ZXT granule intermediates and ZXT granules according to relevant technical requirements;5.Launching primary pharmacodynamics research on ZXT granules by metabolic cage of edema model mice;6.Launching preliminary stability research on ZXT granules according to relevant guiding principles;7.Exploring the quality differences between ZXT granules and Zexie Decoction"standard decoction"under the same quality evaluation method,and verifying the results with pharmacodynamic test.Result:1.The extraction solvent of ZXT granules is ethanol;2.The preparation process of ZXT granules intermediates:adding 6.61 times of 72%ethanol,extracting three times,2.59hours each time,filtering,decompression drying after vacuum concentration at 60?;3.The preparation process of Zexie Decoction"standard decoction":adding 13.41 times of water,extracting three times,2.21 hours each time,filtering,freeze-drying after vacuum concentration at 80?;4.The preparation of ZXT granules:weighing ZXT granule intermediate powder and dextrin(m_ZXT:m_dextrin=2:3),adding absolute ethanol,mixing and making granules;5.Zexie Decoction"standard decoction"and ZXT granule intermediate quality standard:TLC identification,extracting rate?25.29%⁴6.97%,not less than 16.27%?,content determination?Alisol B 23-acetate not less than 111.4?g/g,Atractylode III not less than 178.9?g/g;Alisol B 23-acetate content not less than 1.6 mg/g,Atractylode III not less than 5.2 mg/g?,HPLC fingerprint?similarity 0.673-0.897,similarity 0.884-0.961?,physical fingerprint?similarity 0.647-0.899,similarity 0.876-0.938?,UV-Vis fingerprint?similarity0.886-0.943,similarity 0.912-0.966?;6.ZXT granule quality standard:prescription;preparation;appearance;TLC identification;check;content determination?Alisol B23-acetate no less than 4.7 mg per bag;Atractylode III no less than 14.5 mg per bag?;dissolution rate?Alisol B 23-acetate and Atractylode III dissolve more than 80%at 90minutes?;7.Primary pharmacodynamics:successful replication of mouse edema mode;ethanol is better than water in the extraction of solvent.;medium dose of ZXT granule has better diuretic effect;8.The results of the preliminary stability research of ZXT granules showes that the stability of ZXT granules is good.9.The results of content determination and HPLC fingerprint of ZXT granules and Zexie Decoction"standard decoction"are consistent with diuretic test.Conclusion:In this paper,the part pre-clinical pharmacy research of six new drugs of ZXT granules has been completed.The preparation technology and quality standard of the intermediate and finished products of ZXT granules have been studied.ZXT granules have good diuretic effect in the primary pharmacodynamics researchand good stability,which can provide a theoretical basis for the development of new drugs of ZXT granules.