纳米碳酸钙及脂质体包覆提高淫羊藿苷生物利用度的研究

Study on Icarrin Bioavailability of Enhancement by Using Nanoparticle CaCO_3 and Solid Lipid Nanoparticles Encapsulation

目的:以纳米碳酸钙及脂质体作为药物包覆载体材料,制备淫羊藿苷碳酸钙纳米微球(ICA/CaCO_3)、淫羊藿苷固体纳米脂质体(ICA-SLN),并考察其提高淫羊藿苷(ICA)在大鼠体内生物利用度的作用。为ICA临床剂型的合理使用提供实验基础数据,奠定其进一步的开发基础。方法:分别采用恒温振摇装载法制备ICA/CaCO_3,超声乳化与高温熔融低温固化结合法制备ICA-SLN。并运用LC-MS-MS测定灌胃ICA、ICA/CaCO_3及ICA-SLN后ICA在大鼠体内不同时间点的血药浓度,采用DAS 2.1药动学软件对数据进行统计学处理。结果:通过LC-MS/MS测定血药浓度,DAS 2.1药动学软件计算统计后得到ICA组的半衰期与最大吸收浓度分别为(1.51±0.42)h、(82.9±12.37)ng/m L,ICA/CaCO_3组的半衰期与最大吸收浓度分别为(4.12±1.01)h、(51.1±31.35)ng/m L,ICA-SLN组的半衰期与最大吸收浓度分别为(2.15±0.39)h、(165±25.16)ng/m L。结论:ICA通过纳米碳酸钙及脂质体包附后与ICA原料药相比,ICA原料药在体内的生物利用度得到了进一步的提高。ICA/CaCO_3与ICA原料药相比,其体内的释放时间得到了一定的延迟。从促进口服药物体内吸收率方面,ICA-SLN较ICA原料药有了一定提高,同时也优于ICA/CaCO_3。实验表明ICA/CaCO_3可在一定程度上延缓ICA在大鼠体内的释放,ICA-SLN可在一定程度上提高ICA在大鼠体内的吸收率。

Objective： To establish the preparation process of icarrin nanoparticles by using the nanoparticle CaCO3 and solid lipid nanoparticles, followed by checking the icarrin bioavailability enhancement performance from the icarrin nanoparticles in rats for provide a basis data of ICA drug preparation rational use and further development. Methods ： The ICA was loaded into CaCO3 nanoparticles by simply shaking the CaCO3 powder in ICA solution. For 1CA - SLN prepara- tion, the ultrasonic emulsification was coupled with materials melting at high temperature and solidification at low temper- ature. The rats were intragastrically administered with ICA and ICA/CaCO3and ICA- SLN respectively. The blood con- centration of different time points was tested by liquid chromatography - tandem mass spectroscopy. The data was dealed with pharmacokinetic programme of DAS 2.1. Results ： The results demonstrated that the half - life of ICA and maximum absorption concentration were （ 1.51 ± 0.42） h and （ 82.9 ± 12.37 ） ng/mL, and the half - life of the ICA/CaCO3 and maximum absorption concentration were （4.12± 1.01 ）h and （51. 1 ± 31.35）ng/mL and the half- life of the ICA- SLNnd maximum absorption concentration were （2.15 ± 0.39）h and （165 ± 25.16）ng/mL by the LC -MS/MS deter- mination of blood drug concentration, computational and statistics of DAS 2.1. Conclusion ： Preparation of ICA nanoparti- cles by nano- CaCO3 and solid lipid nanopartieles encapsulation compared with the ICA. It is the bioavailability which has been further improved in vivo. In contrast with ICA, the ICA/CaCO3 better delays the release time in vivo. The pro- moting the oral drug absorption rate of the ICA - SLN is better than that of ICA and also better than that of the ICA/CaCO3. Therefore ,the ICA/CaCO3better delays the release in vivo and the ICA -SLN enhances the ICA absorption rate in rats.