Department of Pharmacology, College of Medicine, Hanyang University, Seoul 04736, Republic of Korea.
Exercise Physiology Lab, Department of Physical Education, Graduate School, Korea University, Seoul 02841, Republic of Korea.
Medicina (Kaunas). 2024 Sep 20;60(9):1538. doi: 10.3390/medicina60091538.
: This study aimed to develop an embolic agent with short-term embolic effects using cilastatin as the basic material. : The particle size distribution of 25 mg cilastatin-based short-term embolic agents was evaluated microscopically under three different mixing conditions. A total of thirty-six healthy male Sprague Dawley rats were divided into four groups. Each group of six rats was injected once into the tail artery with 0.4 mL each of (A) Cilastatin + D-Mannitol Mixture, (B) Iohexol, (C) Prepenem, and (D) embolization promoter (EGgel). : A visual inspection of the tail appearance of rats in each group was performed at 0, 3, 7, 15, and 21 days. At weeks 1 and 3, three rats per group were euthanized, and histopathological analyses were performed on the specimens obtained from each group. No significant differences were observed on day 7, but mild inflammation was observed in Group (D) on day 15. Histopathological inflammation scoring of tail central artery embolization was performed using a six-point scale (from 0 = absent to 5 = marked inflammation). Three groups were formed consisting of six male New Zealand white rabbits each: control, positive control, and test groups. The control group received an Iohexol injection (rabbits: 0.8 mL). The positive control and experimental groups were injected with prepenem and cilastatin/D-mannitol compound, respectively (0.8 mL), and vascular angiography was performed. The order of occlusion progression after embolization was as follows: test group, positive control group, and control group. : We developed a cilastatin/D-mannitol compound that exhibits characteristics of short-term embolization by utilizing the pharmacokinetic properties of cilastatin and the crystalline material D-mannitol. We evaluated its particle size distribution microscopically, conducted histopathological evaluation including inflammation via animal experiments, and assessed the embolization effect.
本研究旨在以克拉维酸钾为基础材料,开发具有短期栓塞效果的栓塞剂。采用显微镜观察了三种不同混合条件下 25mg 克拉维酸钾基短期栓塞剂的粒径分布。将 36 只健康雄性 Sprague Dawley 大鼠随机分为 4 组,每组 6 只大鼠,分别经尾动脉注入 0.4mL 的(A)克拉维酸钾+甘露醇混合物、(B)碘海醇、(C)比阿培南和(D)栓塞促进剂(EGgel)。观察各组大鼠尾外观,于 0、3、7、15 和 21 天进行视觉评估。在第 1 周和第 3 周,每组处死 3 只大鼠,对每组获得的标本进行组织病理学分析。第 7 天未见明显差异,但第 15 天 D 组可见轻度炎症。采用 6 分制(0=无,5=明显炎症)对尾中央动脉栓塞的组织病理学炎症评分进行评估。每组 6 只雄性新西兰白兔分为三组:对照组、阳性对照组和实验组。对照组注射碘海醇(兔:0.8mL),阳性对照组和实验组分别注射比阿培南和克拉维酸钾/甘露醇复合物(0.8mL),并进行血管造影。栓塞后闭塞进展的顺序如下:实验组、阳性对照组和对照组。我们利用克拉维酸钾的药代动力学特性和结晶性物质甘露醇,开发了一种具有短期栓塞特性的克拉维酸钾/甘露醇复合物。我们通过显微镜观察评估了其粒径分布,通过动物实验进行了包括炎症在内的组织病理学评估,并评估了栓塞效果。