Development of nano-micro composite Xiaochaihu decoction granules for enhanced antipyretic and anti-inflammatory...

Traditional liquid decoctions in traditional Chinese medicine (TCM) offer peak efficacy but suffer from physical instability, whereas commercial granules offer stability but often compromise the active nanoscale phase. To bridge this translational gap, a novel "efficacy phase" (EP) state integrating nanophase and suspension features was developed. Here, Xiao-Chai-Hu Decoction efficacy phase (XCHD-EP) was prepared via centrifugation and dialysis. Its solid granule formulation was optimized using Box-Behnken response surface analysis, and quality evaluated via high-performance liquid chromatography (HPLC). A lipopolysaccharide (LPS)-induced rat fever model was utilized to directly compare the in vivo efficacy of XCHD-EP against the raw decoction and commercial granules. Optimal XCHD-EP granules exhibited excellent physical stability. HPLC quantified key components, including baicalin (19.69 mg/g) and saikosaponin A (0.57 mg/g). Pharmacologically, XCHD-EP effectively reversed pyrexia and broadly downregulated key inflammatory mediators (PGE2, NO, cAMP, IL-1β, and IL-6). Crucially, modernized XCHD-EP granules achieved maximal antipyretic and anti-inflammatory efficacies comparable to the freshly prepared raw decoction (p > 0.05), demonstrating robust advantages over existing commercial granules. Grounded strictly in measured physicochemical and functional data, this study successfully translates the pharmacological potency of an unstable decoction into a stable solid form, providing a reliable strategy for TCM modernization.