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
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篇名: 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
TITLE:
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。
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, cmax, AUC0-24 h and AUC0-∞ 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.
期刊: 2019年第30卷第17期
作者: 陆佳璐,邓丽娜
AUTHORS: LU Jialu,DENG Lina
关键字: 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
KEYWORDS: Curcumin; Tryptophan; Co-amorphous; UPLC-MS/MS; Rats; Pharmacokinetics; Dissolution; Bioavailability
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