目的 优化复方巴戟天纳米混悬剂的制备工艺，开展性能表征后的纳米混悬剂预防性治疗记忆衰退型阿尔茨海默病小鼠的药效评价。方法 以复方巴戟天为研究对象，在单因素考察的基础上，通过高压均质法，以稳定剂用量、均质压力、均质次数为影响因素，优化复方巴戟天纳米混悬剂剂型工艺，并对其进行性能表征；运用桨法筛选最佳体外释放介质，考察复方巴戟天纳米混悬剂中多糖的体外释放行为；对制得的纳米混悬剂开展预防性治疗记忆衰退型阿尔茨海默病小鼠的药效实验。结果 确定复方巴戟天纳米混悬剂制剂优化工艺：生药材与大豆卵磷脂的质量比为1∶0.6，高压均质压力为40.0 MPa（400 bar），均质次数为7次。测得纳米混悬剂的粒径为（203.46±2.67）nm，PDI为0.200±0.002。复方巴戟天纳米混悬剂体外最佳释放介质为10 mg/mL SDS水溶液，总多糖的24 h累积释放率达到（72.10±1.19）%。优化纳米混悬剂口服给药30 d后，与模型组比较，小鼠定位航行实验中阳性对照组和复方巴戟天纳米混悬剂中、高剂量组小鼠逃避潜伏期显著缩短（P＜0.05、0.01）。小鼠空间探索实验中阳性对照组、汤剂组和复方巴戟天纳米混悬剂低、中、高剂量组小鼠进入目标象限的次数显著增加，阳性对照组和复方巴戟天纳米混悬剂低、中、高剂量组目标象限游泳路程显著增加（P＜0.05、0.01）。阳性对照组和复方巴戟天纳米混悬剂低、中、高剂量组小鼠海马和前脑皮层乙酰胆碱（acetylcholine，ACh）含量显著升高，阳性对照组和复方巴戟天纳米混悬剂中、高剂量组小鼠海马和前脑皮层胆碱乙酰转移酶（choline acetyltransferase，ChAT）活性显著升高，阳性对照组和复方巴戟天纳米混悬剂中、高剂量组小鼠海马和前脑皮层乙酰胆碱酯酶（acetylcholinesterase，AChE）活性显著降低（P＜0.05、0.01）。结论 复方巴戟天纳米混悬剂的剂型优化工艺合理、可行，制剂性能符合纳米要求，分散均匀稳定，具有缓慢且持续释放的特性，体外释放行为良好，对阿尔茨海默病引发的记忆衰退具有良好的预防作用，且优于优化后的汤剂作用，为传统剂型的现代技术升级提供有益的启示。

Objective To optimize the preparation process of Bajitian Formula (复方巴戟天) nano-suspension and evaluate its pharmacological efficacy in prophylactic treatment for mice with memory-impaired Alzheimer’s disease after performance characterization. Methods Taking Bajitian Formula as the study subject, and based on single-factor analysis, the formulation process of Bajitian Formula nano-suspension was optimized via high-pressure homogenization with stabilizer dosage, homogenization pressure, and number of homogenization cycles as influencing factors, followed by performance characterization. The paddle method was employed to identify the optimal in vitro release medium, and the in vitro release behavior of polysaccharides in the Bajitian Formula nano-suspension was investigated. Pharmacodynamic experiments were performed to evaluate the preventive effect of the nano-suspension on memory impairment in Alzheimer’s disease model mice. Results The optimized formulation process for Bajitian Formula nano-suspension was determined as follows: the mass ratio of crude herbs to soybean lecithin was 1:0.6, high-pressure homogenization pressure was 40.0 MPa (400 bar), and homogenization cycles were 7. The particle size of the nanoparticle suspension was measured as (203.46 ± 2.67) nm, with a PDI of 0.200 ± 0.002. The optimal in vitro release medium was a 10 mg/mL SDS aqueous solution, achieving a cumulative total polysaccharide release rate of (72.10 ± 1.19)% after 24 h. After 30 d of oral administration of the optimized nanoparticle suspension, compared with the model group, the latency period of escape behavior was significantly shortened in both the positive control group and the medium-and high-dose groups of Bajitian Formula nano-suspension in the spatial navigation experiment (P < 0.05, 0.01). In the spatial exploration experiment, the number of target quadrant entries was significantly increased in the positive control group, decoction group, and low-, medium-, and high-dose groups of Bajitian Formula nano-suspension. The swimming distance to target quadrants was significantly increased in the positive control group and low-, medium-, and high-dose groups of Bajitian Formula nano-suspension (P < 0.05, 0.01). In the positive control group and low-, medium-, and high-dose groups of Bajitian Formula nano-suspension, the acetylcholine (ACh) content in the hippocampus and prefrontal cortex was significantly increased. In the positive control group and medium-and high-dose groups of Bajitian Formula nano-suspension, choline acetyltransferase (ChAT) activity in the hippocampus and prefrontal cortex was significantly elevated, while acetylcholinesterase (AChE) activity in these regions was significantly reduced (P < 0.05, 0.01). Conclusion The formulation optimization process of Bajitian Formula nano-suspension is rational and feasible, with preparation properties meeting nanoscale requirements, demonstrating uniform particle dispersion and good stability. Characterized by slow and sustained release, with excellent in vitro release behavior. It exhibits significant preventive effects against memory decline induced by Alzheimer’s disease, surpassing the efficacy of optimized decoction formulations. This study provides a beneficial reference for the modernization and technical upgrading of traditional dosage forms.

R283.6

福建省高校产学合作项目（2021Y4016）；技术创新重点攻关及产业化项目（2023XQ014）