Combinative Approaches of Chemistry, Pharmacology and Toxicology for the Optimal Pharmaceutical Preparation of an Anti-arthritic Chinese Medicine Formulation QFJBT

Objective Qing Fu Juan Bi Tang(QFJBT)is an anti-arthritic Chinese medicine formula consisting of five herbs:Aconiti Lateralis Radix Praeparata(Fu Zi,附子),Sinomenii Caulis(Qing Feng Teng,青风藤),Astragali Radix(Huang Qi,黄芪),Paeoniae Radix Alba(Bai Shao,白芍)and Moutan Cortex(Mu Dan Pi,牡丹皮),which have well-established histories of use for treatment of rheumatic and arthritic diseases.We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis(RA).Methods The combinative approaches of chemical assessment,toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT.Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents,potent anti-inflammatory and antinociceptive activities,and favorable safety profile.Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography(HPLC)demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent.General toxicological studies showed a favorable safety profile of QFJBT.The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose.In the chronic oral toxicity study,the results of laboratory investigation showed that QFJBT at doses of 3.89,6.80 and 9.72 g/kg body weight(equivalent to 40,70 and 100-fold clinical doses,respectively)caused no changes in all hematological parameters and blood biochemical parameters of rats.No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT.Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.