比较研究小檗碱鼻腔给药与口服给药的血药浓度和脑组织含量的动态变化及其生物利用度  

Comparative Study on Dynamic Changes of Berberine Content in Blood and Brain Tissue and Bioavailability by Nasal Drug Delivery and Oral Administration in Rats

作　　者：魏世超 王开富[2] 邹欣[2] 胡晟 徐丽君[2] 姜淑君 李井彬 陆付耳[2] WEI Shichao1 ,WANG Kaifu2 ,ZOU Xin2, HU Sheng3, XU Lijun2 ,JIANG Shujun2, LI Jingbin2, LU Fuer2(1. Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; 2. Institute of Integrative Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China ; 3. Hubwi University of Medicine, Shiyan 442000, Hubei, Chin)

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院中西医结合研究所,湖北武汉430030 [3]湖北医药学院药学院,湖北十堰442000

出　　处：《中华中医药学刊》2018年第5期1039-1043,共5页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81573785)

摘　　要：目的：揭示小檗碱用于脑部疾病药学原理及最佳给药途径。方法：比较小檗碱经鼻腔给药与口服给药后,其在血药浓度和脑组织含量的动态变化,同时比较两种给药方式的生物利用度。通过口服给药和滴鼻给药后不同时间点腹腔静脉取血,8 h时取脑组织,应用高效液相色谱法（HPLC）测定血浆和脑组织中小檗碱的含量,采用DAS 2.0药代动力学软件分析,绘制药时曲线,计算脑沉积量及生物利用度。结果：BER以187.5 mg·kg^-1剂量口服给药后,其血药浓度于1 h及第3 h出现2个峰值（89.3μg·L^-1,75.1μg·L^-1）,以后大幅下降,其在脑组织的沉积量于3 h达峰值（52.55μg·L^-1）,且平稳维持至8 h;而BER以18.75 mg·kg^-1剂量鼻腔给药后,其血药浓度于8 h内基本稳定在10-20μg·L^-1之间,其在脑组织的沉积量于3-8 h平稳维持在20μg·L^-1左右,鼻腔给药组的血液及脑组织生物利用度均显著高于口服给药组,且脑组织生物利用度鼻腔给药组为口服给药组的10倍以上。结论：BER鼻腔给药较口服给药其血药浓度及脑组织的沉积量较平稳,生物利用度高,但因受到给药剂量的限制,鼻腔给药组脑组织沉积量低于口服给药组。Objective：To reveal the pharmaceutical mechanism and the best administration route of berberine for brain diseases. Methods： Compare the dynamic changes of berberine content in blood and brain tissue and the bioavailability by nasal drug delivery and oral administration in rats. Take blood from abdominal venous in different time points and take out the brain tissue at 8 h after nasal drug delivery and oral administration in rats,and determine the content of BER in plasma and brain tissue by HPLC. Curve concentration-time of BER by pharmacokinetic software DAS 2. 0,and calculate the bioavailability and the deposit amount of BER in brain. Results： After oral administration（187. 5 mg · kg^-1）,the BER blood concentration appeared two peaks（89. 3 μg·L-（-1）,75. 1 μg·L-（-1））at 1 h and 3 h and then fell dowen sharply. The BER content in brain appeared a peak（52. 55 μg·L-（-1）） at 3 h and then maintained to 8 h. After nasal drug delivery（18. 75 mg·kg^-1）. The BER blood concentration maintained 10-20 μg·L-（-1） within 8 h,and the BER content in brain maintained about 20 μg·L-（-1） in 3 h to 8 h. The bioavailabilities of blood and brain by nasal drug delivery were significantly higher than that by oral administration,however,the bioavailabilities of brain in nasal drug delivery group was more than 10 times of that in oral administration group. Conclusion： The blood concentration and the deposit amount in brain of BER kept more steady by nasal drug delivery than those by oral administration,and the bioavailabilities of BER by nasal drug delivery was higher than that by oral administration. The brain tissue deposition amount of BER in nasal drug delivery group is lower than in oral administration group due to the small drug dose for nasal drug delivery.

关 键 词：小檗碱 鼻腔给药 口服给药 药代动力学 

分 类 号：R285.5[医药卫生—中药学]