摘要
Carrier-free co-amorphous breviscapine-huperzine A via solvent evaporation. • DFT and multi-spectra show H-bonding and π–π stacking stabilize amorphization. • Aqueous solubility of both compounds is significantly enhanced. • Synergistic antioxidant and AChE inhibition suggest multi-target Alzheimer’s potential. Both breviscapine and huperzine A have antioxidant effects, and huperzine A has excellent anticholinesterase effect. Poor aqueous solubility and limited bioavailability of natural products remain major obstacles in drug development. We report the first systematic investigation of a co-amorphous system composed of breviscapine and huperzine A fabricated by solvent evaporation without polymeric carriers. Polarized-light microscopy, thermal and crystallographic analysis confirmed complete amorphization. Density functional theory (DFT) calculations demonstrated strong non-covalent stabilization of the BRE–HupA dimer, and multi-spectral characterization further confirmed supramolecular interactions of hydrogen bonding and π–π stacking. Apparent solubility in water and artificial nasal fluid rose 41- and 65-fold for BRE, respectively, and 2-fold for HupA. The system exhibited reduced hygroscopicity and excellent stability under accelerated storage (40 °C/75% RH, 12 weeks). Biological evaluation revealed superior antioxidant performance in DPPH, superoxide, and hydroxyl radical assays, alongside stronger acetylcholinesterase inhibition compared to raw drugs and their physical mixture. These findings highlight the critical role of non-covalent interactions in stabilizing the co-amorphous state and demonstrate the dual benefit of solubility enhancement and pharmacological synergy. The BRE–HupA co-amorphous system provides a promising carrier-free strategy for developing multi-target formulations against Alzheimer’s disease and related neurodegenerative disorders. Download: Download high-res image (278KB) Download: Download full-size image
危险品化学品经营许可证（带存储）