中成药2023，Vol.45Issue(12)：3872-3878,7.DOI:10.3969/j.issn.1001-1528.2023.12.002
葫芦素B纳米混悬剂制备及其体内药动学研究
Preparation and in vivo pharmacokinetics of cucurbitacin B nanosuspensions
摘要
Abstract
AIM To prepare cucurbitacin B nanosuspensions,and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method.With stabilizer type,stabilizer-drug ratio and homogeneous frequency as influencing factors,particle size and PDI as evaluation indices,the formulation was optimized by single factor test,after which the solubility and stability were determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of cucurbitacin B,physical mixture and cucurbitacin B nanosuspensions(10 mg/kg),respectively,after which blood collection was made at 0.5,1,2,3,4,8,10,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of cucurbitacin B,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was hydroxypropyl cellulose+sodium dodecyl sulfate(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-drug ratio,80 MPa for homogeneous pressure,and 12 times for homogeneous frequency,the average particle size,PDI and Zeta potential were 200 nm,0.140 and-32 mV,respectively.The nanosuspensions demonstrated obviously higher solubility than that of raw medicine and physical mixture,along with good stability within 6 months.Cucurbitacin B existed in the nanosuspensions in an amorphous state.Compared with raw medicine and physical mixture,the nanosuspensions displayed shortened tmax(P<0.01),prolonged t1/2(P<0.05,P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 4.32 times as compared with that of raw medicine.CONCLUSION Nanosuspensions can improve the dissolution rate and oral bioavailability of cucurbitacin B.关键词
葫芦素B/纳米混悬剂/制备/体内药动学/高压均质法/UPLC-MS/MSKey words
cucurbitacin B/nanosuspensions/preparation/in vivo pharmacokinetics/high-pressure homogenization method/UPLC-MS/MS分类
医药卫生引用本文复制引用
陈容,田莉,薛晓菲,潘思影,杨雪,田青..葫芦素B纳米混悬剂制备及其体内药动学研究[J].中成药,2023,45(12):3872-3878,7.基金项目
河南省高等学校重点科研项目(17B320022) （17B320022）
