Study On Patchoulone Derivative PPCl Tablets And Synthesis Of Tryptanthrin Spiro-ring Derivatives

Objective: 1.Patchoulone is one of the main active ingredients of Patchouli,which has various pharmacological effects such as antibacterial,insecticidal,anti-inflammatory,immunosuppressive,gastroenteric protection,and so on,and patchoulone derivative（6-methyl-4’-hydroxy-3-5’-p-chlorophenyl-2’,4’-dien-1’-pentanoylpyran-2-one,PPCl）,were chemically modified from patchoulone.After previous systematic research,it is believed that it has a certain drug potential.Therefore,this paper intends to explore the physical and chemical properties of the APIs and the preparation process of its tablets,which provide theoretical basis and reference methods for subsequent drug development research.2.Based on the previous research on the drug potential of patchoulone derivatives,this work designs structural modifications to other active ingredients of traditional Chinese medicine to obtain derivatives with certain biological activity and provide a certain research basis.The indolequinazolone alkaloids tryptanthrin and its derivatives derived from traditional Chinese medicine are very valuable natural products,mainly because of the excellent multiple pharmacological activities of tryptanthrin.This work intends to complete the construction of a series of tryptanthrin spiro-ring skeletons by organic synthesis,which provide the necessary material basis for the design and discovery of leading compounds with superior activity.Methods: 1.Pre-prescription studies was the first conducted work,including the study of physicochemical properties of APIs and the compatibility of raw materials with excipients.Following works were prescription screening of tablets,and the quality study of tablets.2.First,using tryptanthrin and vinylethylene carbonates as starting substrates,to establish the optimal reaction conditions,and complet the construction of the tryptanthrin spiro-ring skeletons.Subsequently,using asymmetric catalysis to achieve the construction of the chiral tryptanthrin spiro-ring drug-like skeletons.Finally,preliminarily exploring the pharmacological activity of tryptanthrin spiro-ring derivatives by in vitro antibacterial experiments.Results: 1.The best prescription of PPCl tablets: PPCl 50 mg,microcrystalline cellulose160 mg,lactose 80 mg,3% hypromellose appropriate amount,carboxymethyl cellulose sodium 3%,magnesium stearate 0.5%,sodium lauryl sulfate 1%.The preparation process is wet granulation.The quality inspection results of PPCl tablets are in compliance with regulations.2.This work completed the construction of a series of tryptanthrin spiro-ring derivatives,and some of the tryptanthrin derivatives showed certain antibacterial activity.Conclusion: 1.PPCl tablet is an innovative drug formulation with stable and feasible preparation process,and the quality inspection results all meet the requirements.2.The library of tryptanthrin spiro-ring derivatives were established,and some tryptanthrin derivatives showed certain antibacterial activity against the tested bacteria.