异烟肼-柚皮素共晶的表征及其性能研究

Characterization and performance of naringenin-isoniazid cocrystal

以抗结核药异烟肼和黄酮类天然产物柚皮素为原料,采用混悬法制得异烟肼-柚皮素的药物-药物共晶。通过XRPD、DSC、FTIR、SSNMR和LNMR等分析技术对共晶产物进行了表征,分析了共晶分子间的氢键作用,确定了共晶中异烟肼和柚皮素的比例;对异烟肼、柚皮素和共晶在模拟生理液中的表观平衡溶解度进行了比较研究。结果表明,异烟肼的酰肼基和吡啶氮与柚皮素上的3个羟基在共晶中形成了新的氢键,共晶产物中异烟肼与柚皮素的摩尔比为1∶1;共晶能大幅降低异烟肼的表观平衡溶解度,提高柚皮素的表观平衡溶解度,说明所得共晶能够在保留异烟肼抗结核药效的同时,减弱肝损伤,药理作用明显。

The drug-drug cocrystal of isoniazid（INZ）,an anti-tuberculosis drug,and naringenin（NAR）,a flavonoid natural product,was manufactured by the slurry method.The formation and interaction of hydrogen bonds between INZ and NAR molecules in the cocrystal were characterized by powder XRD,DSC,FTIR,SSNMR,and LNMR,and then the molar ratio of INZ and NAR was determined.In addition,the equilibrium solubility of INZ,NAR,and cocrystal in simulated physiological fluids was determined experimentally.The results indicate that new hydrogen bonds are formed between the hydrazide,pyridine nitrogen of INZ molecular and the three hydroxyls of NAR molecular in the cocrystal,and the molar ratio of INZ and NAR in the cocrystal is 1∶1.The apparent equilibrium solubility of INZ reduces substantially while NAR improves,indicating that the obtained cocrystal can attenuate liver damage while preserving the anti-tuberculosis efficacy of isoniazid,and the pharmacological action is obvious.