中国中药杂志

2019, v.44(13) 2841-2848

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N-乙酰-L-半胱氨酸对姜黄素鼻腔给药生物利用度及脑组织分布的影响
Effect of N-acetyl-L-cysteine on bioavailability and brain distribution of curcumin by nasal delivery

苏文强;尉桐欣;经杰;孟治平;陈轩宇;吴欣欣;朱华旭;付廷明;
SU Wen-qiang;WEI Tong-xin;JING Jie;MENG Zhi-ping;CHEN Xuan-yu;WU Xin-xin;ZHU Hua-xu;FU Ting-ming;College of Pharmacy,Nanjing University of Chinese Medicine;

摘要(Abstract):

姜黄素(curcumin)是从中药材植物根或块茎中提取分离出来的一种天然活性物质,具有抗炎、抗肿瘤等活性,同时对脑部疾病有一定的疗效。该文采用气流粉碎法制备姜黄素原料药,加液共磨法将N-乙酰-L-半胱氨酸(NAC)作为吸收促进剂与姜黄素制备形成姜黄素-NAC混合物样品。通过X射线衍射(XRD),差式扫描热分析(DSC),溶出杯浆法等对原料和产物进行表征,发现研磨法制备的样品原特征峰明显,熔融温度、累积溶出度未明显改变,样品仍为原型并未形成新的晶型。将2种药物分别进行鼻腔给药,鼻腔给药后在相应时间点进行眼眶取血与脑组织分离,采用UPLC-MS/MS法测定大鼠血浆及脑组织中药物含量,对比观察在不同时间段姜黄素在血浆和脑组织中的吸收分布情况。通过鼻腔分别给予2种药物后发现,在吸收促进剂的作用下鼻腔吸入混合物后血浆中的姜黄素浓度较高,药动学参数Cmax,AUC显著增大。脑组织方面,嗅球、海马、脑桥组织部位药物浓度有明显提高。在0. 083~0. 5 h,嗅球、梨状叶和海马始终保持高浓度,1~3 h皮层、纹状体、下丘脑、中脑达到了较高的浓度,3~7 h小脑、脑桥、延脑部位维持了相对较高的浓度。研究表明鼻腔给予姜黄素-NAC混合物能明显提高姜黄素的生物利用度,并具有明显的脑组织分布差异。
Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.

关键词(KeyWords): 姜黄素;N-乙酰-L-半胱氨酸;鼻腔给药;脑组织;脑靶向
curcumin;N-acetyl-L-cysteine;intranasal;brain tissues;brain-targeted

Abstract:

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基金项目(Foundation): 国家自然科学基金项目(81873013);; 江苏省中药学优势学科项目

作者(Author): 苏文强;尉桐欣;经杰;孟治平;陈轩宇;吴欣欣;朱华旭;付廷明;
SU Wen-qiang;WEI Tong-xin;JING Jie;MENG Zhi-ping;CHEN Xuan-yu;WU Xin-xin;ZHU Hua-xu;FU Ting-ming;College of Pharmacy,Nanjing University of Chinese Medicine;

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