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晶型对落新妇苷纳米混悬剂体内外行为的影响
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| 篇名： | 晶型对落新妇苷纳米混悬剂体内外行为的影响 |
| TITLE： | |
| 摘要： | 目的：探讨晶型对落新妇苷纳米混悬剂（AT-NS）体内外行为的影响。方法：分别采用沉淀法和微型化介质研磨法制备两种AT-NS，即AT-NS1和AT-NS2，采用纳米激光粒度仪测定其粒径和多分散性指数（PDI）；通过X射线衍射技术（XRD）、电镜扫描技术（SEM）、高效液相色谱法（HPLC）和桨法对AT原料药、AT-NS1、AT-NS2的结构特征、外观形态及体外溶出度进行分析、比较。取15只健康雄性SD大鼠随机分为AT原料药组、AT-NS1组和AT-NS2组，每组5只。分别单次灌胃相应药物混悬液120 mg/kg（均以水为溶剂），并于给药前（0 min）及给药后5、10、20、30、60、120、240、480 min自眼眶取血，以芦丁为内标，采用HPLC法测定大鼠血浆中AT的质量浓度，采用DAS 2.0软件计算其药动学参数，并进行比较。结果：AT-NS1和AT-NS2粒径分别为（212.48±0.32）、（226.36±2.29）nm，PDI分别为0.129 3±0.026 3、0.254 7±0.012 4。XRD分析显示，AT-NS1为无定型，AT-NS2为结晶型，两者的衍射峰均与AT原料药存在差异。SEM分析显示，AT-NS1和AT-NS2形态相似，均呈圆球状且大小均一；AT原料药为块状，粒径较大且大小不一。溶出度试验结果显示，1 h时，AT原料药、AT-NS1和AT-NS2的累积溶出度分别为4.54％、35.01％、12.22％；12 h时，三者的累积溶出度分别为24.01％、81.14％、64.69％；24 h时，三者的累积溶出度分别达到36.04％、84.87％、85.86％。药动学研究结果显示，与原料药组比较，AT-NS1组和AT-NS2组大鼠的cmax、AUC0-∞以及AT-NS1组的t1/2z均显著升高，AT-NS1组大鼠的tmax显著缩短（P＜0.05）；与AT-NS2组比较，AT-NS1组大鼠的cmax、AUC0-∞、t1/2z均显著升高，tmax显著缩短（P＜0.05）。结论：将AT制备成NS后，可明显增加其体外溶出，并促进其体内口服吸收；且在短时间内，无定型NS比结晶型NS的溶出/吸收更快。 |
| ABSTRACT： | OBJECTIVE： To investigate the effects of crystal form on in vivo and in vitro behavior of Astilbin nanosuspensions （AT-NS）. METHODS： AT-NS1 and AT-NS2 were prepared by precipitation method and miniaturized media milling method respectively. The particle size and polydispersity index （PDI） were determined by laser particle size analyzer. X-ray diffraction （XRD）， scanning electron microscopy （SEM）， HPLC and paddle method were used to analyze and compare the structure characteristics， appearance morphology and in vitro dissolution of AT raw material， AT-NS1 and AT-NS2. Totally 15 healthy male SD rats were randomly divided into AT raw material， AT-NS1 and AT-NS2 group， with 5 rats in each group. They were given relevant medicine suspension 120 mg/kg （using water as solvent） intragastrically； blood samples were collected from orbit before medication （0 min） and 5， 10， 20， 30， 60， 120， 240， 480 min after medication. Using rutin as internal standard， HPLC method was used to determine plasma concentration of AT in rats. Pharmacokinetic parameters were calculated by using DAS 2.0 software and then compared. RESULTS： The particle sizes of AT-NS1 and AT-NS2 were （212.48±0.32） nm and （226.36±2.29） nm， respectively； PDI were 0.129 3±0.026 3 and 0.254 7±0.012 4. XRD analysis showed AT-NS1 was amorphous， and AT-NS2 was crystalline. Diffraction peaks of both were different from those of AT raw material. SEM analysis showed that AT-NS1 and AT-NS2 were similar in morphology， and they were spherical and uniform in size； AT raw material was lump with large particle size and different sizes. Results of dissolution tests showed that accumulative dissolution of AT raw material， AT-NS1 and AT-NS2 were 4.54％， 35.01％， 12.22％ at 1 h； accumulative dissolution of them were 24.01％， 81.14％， 64.69％ at 12 h； accumulative dissolution of them were 36.04％， 84.47％， 85.86％ at 24 h， respectively. Results of pharmacokinetic study showed， compared with AT raw material group， cmax and AUC0-∞ of AT-NS1 and AT-NS2 groups as well as t1/2z of AT-NS1 group were increased significantly， while tmax of AT-NS1 group was significantly reduced significantly （P＜0.05）. Compared with AT-NS2 goup， cmax， AUC0-∞ and t1/2z of AT-NS1 group were increased significantly， while tmax was reduced significantly （P＜0.05）. CONCLUSIONS： When AT is prepared into NS， dissolution in vitro and oral absorption in vivo of AT are increased significantly. In a short time， the dissolution/absorption of amorphous NS is faster than crystalline NS. |
| 期刊： | 2019年第30卷第4期 |
| 作者： | 汪小涵，王聪颖，刘肖，沈成英，钟芮娜，申宝德，袁海龙 |
| AUTHORS： | WANG Xiaohan，WANG Congying，LIU Xiao，SHEN Chengying，ZHONG Ruina，SHEN Baode，YUAN Hailong |
| 关键字： | 落新妇苷；纳米混悬剂；无定型；结晶型；溶出度；药动学 |
| KEYWORDS： | Astilbin； Nanosuspensions； Amorphous； Crystalline； Dissolution； Pharmacokinetics |
| 阅读数： | 369 次 |
| 本月下载数： | 3 次 |
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