黄豆苷元介孔二氧化硅纳米粒缓释片制备及口服药动学研究  

Preparation and oral pharmacokinetics of daidzein mesoporous silica nanoparticles sustained-release tablet

作　　者：唐静 张付利 决利利[4] 王美丽 郭娟娟 王晓静 TANG Jing;ZHANG Fuli;JUE Lili;WANG Meili;GUO Juanjuan;WANG Xiaojing(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Malaysia MAHSA University,Selangor Bandar Saujana Putra 42610,Malaysia;Henan University,Kaifeng 475001,China;Zhengzhou University of Industrial Technology,Zhengzhou 451150,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]Malaysia MAHSA University,Selangor Bandar Saujana Putra 42610 [3]河南大学,河南开封475001 [4]郑州工业应用技术学院,河南郑州451150

出　　处：《中草药》2024年第14期4700-4710,共11页Chinese Traditional and Herbal Drugs

基　　金：河南省高等学校重点科研项目计划(23B310010)。

摘　　要：目的制备黄豆苷元介孔二氧化硅纳米粒缓释片(daidzein mesoporous silica nanoparticles sustained-release tablets,Dai-MSNs-SRT),并考察Beagle犬的口服药动学行为。方法选择羟丙基甲基纤维素K4M(hydroxypropyl methyl cellulose K4M,HPMC K4M)用量、羧甲基淀粉钠(carboxyl methyl starch sodium,CMS-Na)用量和聚乙二醇400(polyethylene glycol400,PEG 400)用量为主要影响因素,Dai-MSNs-SRT在2、6、12 h累积释放率的综合评分为响应值,采用Box-Behnken设计-效应面法优化IMP-SD-HMSRT最佳处方优化处方工艺。对Dai-MSNs-SRT释药模型和释药机制进行探讨。按10 mg/kg(以黄豆苷元计)进行ig,比较Dai-MSNs-SRT口服药动学行为,并计算相对口服生物利用度。采用Loo-Rigelman法评价Dai-MSNs-SRT体内外相关性。结果Dai-MSNs-SRT最佳处方为Dai-MSNs粉末350 mg/片,HPMC K4M用量为15.2%,CMS-Na用量为9.5%,PEG 400用量为2.1%。Dai-MSNs-SRT缓释特征明显,12 h累积释放率达94.87%。Dai-MSNs-SRT体外释药符合Higuchi模型,释药机制为扩散和骨架溶蚀并存。药动学结果显示,Dai-MSNs-SRT血药浓度(C_(max))波动幅度小,达峰时间(t_(max))由(1.53±0.42)h延后至(4.26±0.44)h,半衰期(t_(1/2))由(3.26±0.56)h延长至(6.63±2.17)h,与上市品相比,相对生物利用度提高至其1.88倍。Dai-MSNs-SRT在pH7.4磷酸盐缓冲液中体外释放与体内吸收相关性良好。结论Dai-MSNs-SRT工艺重复性良好,C_(max)波动幅度小,提高了其生物利用度。Objective To prepare daidzein mesoporous silica nanoparticles sustained-release tablets(Dai-MSNs-SRT),and investigate its oral pharmacokinetic behavior in Beagle dogs.Methods Hydroxypropyl methyl cellulose K4M(HPMC K4M) dose,carboxyl methyl starch sodium(CMS-Na) dose and polyethylene glycol 400(PEG 400) dose were selected as main influencing factors,composite score of cumulative rate of 2,6,and 12 h was used as response value,Box-Behnken design-response surface methodology(BBD-RSM) was employed to optimize formulation of Dai-MSNs-SRT.Release model and release mechanism were also studied.DaiMSNs-SRT was orally administered to Beagle dogs(10 mg/kg),pharmacokinetic behavior of Dai-MSNs-SRT was compared and relative oral bioavailability was calculated.Loo-Rigelman method was used for the evaluation of in vivo and in vitro correlation.Results Optimal formulation of Dai-MSNs-SRT:Dai-MSNs powder was 350 mg/tablet,HPMC K4M dose was 15.2%,CMS-Na dose was 9.5% and PEG 400 dose was 2.1%.Sustained-release characteristic of Dai-MSNs-SRT was obvious and cumulative release rate in 12 h was up to 94.87%.Drug release in vitro of Dai-MSNs-SRT was better accorded with Higuchi model,and release mechanism was diffusion and matrix degradation.Pharmacokinetic results showed that C_(max) of Dai-MSNs-SRT fluctuated slightly,t_(max) was delayed from(1.53 ± 0.42) h to(4.26 ± 0.44) h and t_(1/2) was prolonged from(3.26 ± 0.56) h to(6.63 ± 2.17) h.Relative bioavailability of DaiMSNs-SRT was enhanced to 1.88 times comparing to commercial tablets.In vitro release behavior of Dai-MSNs-SRT in pH 7.4 phosphate buffer saline was better associated with its absorption in vivo.Conclusion Reproducibility of Dai-MSNs-SRT was favorable,C_(max) fluctuated slightly and relative bioavailability was also enhanced.

关 键 词：黄豆苷元 介孔二氧化硅纳米粒 缓释片 Box-Behnken设计-效应面法 药动学 生物利用度 

分 类 号：R283.6[医药卫生—中药学]