[关键词]
[摘要]
目的 优化“护肝I号”口崩片处方及制备工艺,并考察其对小鼠急性肝损伤的保护作用。方法 对崩解剂、润滑剂、填充剂进行单因素筛选,以片剂外观、硬度、脆碎度、崩解时间作为综合评价指标,选取崩解剂、微粉硅胶、硬脂酸镁三者用量为考察因素,采用Box-Behnken响应面法设计优化制备工艺。以一次性大剂量ig给予对乙酰氨基酚(acetaminophen,APAP,500 mg/kg)复制小鼠急性肝损伤模型,考察口崩片对血清中丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)活性、肝组织中还原型谷胱甘肽(GSH)和丙二醛(MDA)含量及肝组织形态学变化的影响。结果 最优处方为干膏粉22.00%、微晶纤维素18.00%、山梨醇20.00%、甘露醇16.00%、阿斯巴甜0.50%、柠檬酸0.50%、L-HPC 20.00%、微粉硅胶2.50%、硬脂酸镁0.50%,以此处方制备口崩片的硬度为4~7 kg,平均崩解时间50 s,平均脆碎度0.85%;与模型组相比,联苯双酯对照组、“护肝I号”水煎液组和“护肝I号”口崩片组小鼠血清中2种转氨酶ALT、AST含量明显降低,存在显著性差异(P<0.01);肝组织中MDA含量降低,存在显著性差异(P<0.01),显著改善APAP对肝组织的破坏。结论 “护肝I号”口崩片处方工艺可行、操作简便,与“护肝I号”水煎液均能有效预防APAP导致的肝损伤,且两者药效作用差异无显著性。
[Key word]
[Abstract]
Objective To optimize the prescription and preparation process of "Hugan I" Orally Disintegrating Tablets, and investigate its efficacy against acute liver injury in mice. Methods Single factor method was used for disintegrants, lubricants, and fillers screening. Taking the appearance, hardness, friability and disintegration time of the tablets as the comprehensive evaluation index, the dosage of disintegrant, micro-silica gel and magnesium stearate was selected as the investigation factor. The Box-Behnken response surface method was used to optimize the orally disintegrating tablets. Acetaminophen (APAP, 500 mg/kg) was used to replicate acute liver injury model by one-time high-dose intragastric administration to investigate the effects of orally disintegrating tablets on the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the content of glutathione (GSH) and malondialdehyde (MDA) and morphological changes in liver tissue. Results The optimal prescription was as following:dry paste powder 22.00%, microcrystalline cellulose 18.00%, sorbitol 20.00%, mannitol 16.00%, Aspartame 0.50%, citric acid 0.50%, disintegration agent L-HPC 20.00%, micro-powder silica gel 2.50% and magnesium stearate 0.50%. The hardness of the orally disintegrating tablets was 4-7 kg, the mean disintegration time was about 50 s, and the mean friability was around 0.85%. Compared with the model group, there were significant differences (P<0.01) in Biphenyl diester control group, "Hugan I" Decoction group and "Hugan I" Orally Disintegrating Tablets group, and the levels of ALT and AST in the serum of the mice were significantly decreased, The content of MDA in the liver tissue was decreased, which improved the damage of APAP to liver tissue. Conclusion The formulation of the "Hugan I" Orally Disintegrating Tablet is feasible and easy to operate, which achieves the same effect with "Hugan I" Decoction that effectively prevent liver damage caused by acetaminophen with no significant differences.
[中图分类号]
R283.6
[基金项目]
孙宝惠全国名老中医药专家传承工作室(7002016008005)