Page 49 - 2019年9月第30卷第17期

姜黄素-色氨酸共无定型的制备及其在大鼠体内的药动学研究

陆佳璐 ，邓丽娜（南京中医药大学附属张家港医院药学部，江苏 张家港 215600）
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中图分类号 R944.9；R965 文献标志码 A 文章编号 1001-0408（2019）17-2348-07
DOI 10.6039/j.issn.1001-0408.2019.17.09

摘 要 目的：制备姜黄素（CUR）-色氨酸（TRY）共无定型（Co-amorphous CUR-TRY），并研究其在大鼠体内的药动学特征。方
法：采用球磨法制备Co-amorphous CUR-TRY；利用差示扫描量热分析法和粉末X射线衍射法对Co-amorphous CUR-TRY进行表
征分析，并于漏槽和非漏槽条件下比较Co-amorphous CUR-TRY、CUR原料药、CUR-TRY物理混合物的体外溶出率（溶出度）。取
18只SD大鼠，随机分为Co-amorphous CUR-TRY组（155.43 mg/kg）、CUR原料药组（100 mg/kg）、CUR-TRY物理混合物组（155.43
mg/kg），每组 6 只，灌胃给药 1 次，于给药后 0.167、0.33、0.5、0.75、1、1.5、2、4、6、8、10、12、24 h 从各组大鼠眼眶静脉丛取血约 0.3
mL，采用超高效液相色谱-串联质谱法测定大鼠血浆中CUR的浓度，并应用DAS 3.0软件进行药动学研究。结果：差示扫描量热
分析和粉末X射线衍射结果表明成功制备Co-amorphous CUR-TRY。漏槽条件下（120 min时），与CUR原料药[CUR累积溶出率
为（36.79±3.79）％]和 CUR-TRY 物理混合物[CUR 累积溶出率为（33.12±0.68）％]比较，Co-amorphous CUR-TRY 中 CUR 的累积
溶出率[（90.37±2.52）％]显著提高（P＜0.01）。非漏槽条件下，与 CUR 原料药和 CUR-TRY 物理混合物比较，Co-amorphous
CUR-TRY中CUR具有较高的溶出度，并且维持长时间的超饱和程度。药动学实验结果显示，与CUR原料药组和CUR-TRY物理
混合物组比较，Co-amorphous CUR-TRY 组 cmax、AUC0-24 h、AUC0-∞显著增加（P＜0.01），CUR 的相对生物利用度分别提高了 2.14、
1.86倍（P＜0.01）。结论：本研究制备的Co-amorphous CUR-TRY能有效提高CUR的体外溶出度及大鼠体内生物利用度。
关键词 姜黄素；色氨酸；共无定型；超高效液相色谱-串联质谱法；大鼠；药动学；溶出度；生物利用度

Preparation of Co-amorphous Curcumin-tryptophan and Its Pharmacokinetic Study in Rats
LU Jialu，DENG Lina（Dept. of Pharmacy，Zhangjiagang Hospital Affiliated to Nanjing University of TCM，
Jiangsu Zhangjiagang 215600，China）

ABSTRACT OBJECTIVE：To prepare Co-amorphous curcumin（CUR）-tryptophan（TRY）（Co-amorphous CUR-TRY），and to
study its pharmacokinetic characteristics in rats. METHODS：Co-amorphous CUR-TRY was prepared by ball milling method.
differential scanning calorimetry（DSC）and powder X-ray diffraction（XRD）were used to characterize Co-amorphous CUR-TRY.
The in vitro dissolution rate （dissolution） of Co-amorphous CUR-TRY，CUR and CUR-TRY physical mixture were compared
under sink condition and non-sink condition. 18 SD rats were selected and randomly divided into Co-amorphous CUR-TRY group
（155.43 mg/kg），CUR raw material group（100 mg/kg），CUR-TRY physical mixture group（155.43 mg/kg），with 6 rats in each
group. They were given relevant medicine intragastrically once. Each blood samples 0.3 mL were collected from orbital venous
plexus 0.167，0.33，0.5，0.75，1，1.5，2，4，6，8，10，12，24 h after medication. UPLC-MS/MS was used to determine plasma
concentration of CUR in rats. The pharmacokinetic study was performed by using DAS 3.0 software. RESULTS：DSC and XRD
showed that Co-amorphous CUR-TRY was successfully prepared. Under sink condition （120 min），compared with CUR raw
material [cumulative dissolution rate of CUR is（36.79±3.79）％] and CUR-TRY physical mixture [cumulative dissolution rate of
CUR is （33.12 ± 0.68）％ ]，cumulative dissolution rate of CUR in Co-amorphous CUR-TRY（90.37 ± 2.52）％ was improved
significantly（P＜0.01）. Under non-sink condition，compared with CUR raw material and CUR-TRY physical mixture，CUR of
Co-amorphous CUR-TRY exhibited dissolution and maintained supersaturation for a long time. Pharmacokinetic study showed that
compared with CUR raw material group and CUR-TRY physical mixture group，c max，AUC 0-24 h and AUC 0-∞ were increased
significantly in Co-amorphous CUR-TRY group（P＜0.01）；Relative bioavailability of CUR was improved by 2.14 and 1.86 fold
（P＜0.01）. CONCLUSIONS：Prepared Co-amorphous CUR-TRY can effectively improve in vitro dissolution and in vivo
bioavailability in rats of CUR.
KEYWORDS Curcumin；Tryptophan；Co-amorphous；UPLC-MS/MS；Rats；Pharmacokinetics；Dissolution；Bioavailability

姜黄素（CUR）是从姜科植物姜黄（Curcumin longa
＊中药师。研究方向：药物制剂。E-mail：921981542@qq.com [1-2]
# 通信作者：主管中药师。研究方向：药物制剂与药动学。E- L.）中提取的一种相对分子质量小的多酚类物质 ，其
mail：986178291@qq.com 药理作用广泛，主要用于抗炎、抗癌、降血脂等 [3-8] ；但

·2348 · China Pharmacy 2019 Vol. 30 No. 17 中国药房 2019年第30卷第17期