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基于碘代氰基丙烯酸酯的新型液体栓塞剂,具有内在的放射显影性,用于血管内栓塞。

Iodinated Cyanoacrylate-Based Novel Liquid Embolic Compositions with Inherent Radiopacity for Endovascular Embolization.

机构信息

Research Institute of Advanced Materials (RIAM), Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, Republic of Korea.

出版信息

Adv Healthc Mater. 2024 Nov;13(29):e2401099. doi: 10.1002/adhm.202401099. Epub 2024 Sep 5.

Abstract

Endovascular embolization is a promising therapeutic approach broadening its application area due to its minimal invasiveness and short operation time, wherein lesional blood vessels are occluded with liquid embolic agents under X-ray imaging guidance. Histoacryl and its composition with Lipiodol are one of the most widely used liquid embolic agents, however, Histoacryl has critical limitations, such as lack of innate X-ray visibility and strong adhesion to microcatheter. In this study, three different iodinated cyanoacrylates are newly synthesized as alternatives to Histoacryl and employed to develop liquid embolic compositions. Among them, 4-iodobutyl 2-cyanoacrylate (IBCA) is most preferable with high iodine content (730 mgI mL) and fast polymerization. The IBCA-based embolic compositions containing ethyl oleate and acetic acid showed moderate viscosity and reduced catheter adhesiveness (≈0.80 N), and their polymerization time is freely controllable from 2 to 15 s. In the embolization test with rabbit models, the renal artery is successfully occluded by IBCA-based embolic compositions without vascular recanalization or nontarget embolization for 4 w. Their embolic effect is further evaluated using swine models, demonstrating the practical applicability in the clinic. In conclusion, IBCA and its compositions are determined to have great potential as novel liquid embolic agents.

摘要

血管内栓塞是一种有前途的治疗方法,由于其微创和手术时间短,应用范围不断扩大,其中通过 X 射线成像引导用液体栓塞剂闭塞病变血管。Histoacryl 及其与 Lipiodol 的组合物是最广泛使用的液体栓塞剂之一,然而,Histoacryl 具有关键的局限性,例如缺乏先天的 X 射线可见性和对微导管的强烈粘附性。在这项研究中,新合成了三种不同的碘化氰基丙烯酸酯作为 Histoacryl 的替代品,并用于开发液体栓塞组合物。其中,4-碘丁基 2-氰基丙烯酸酯(IBCA)具有最高的碘含量(730mgI/mL)和快速聚合性,是最优选的。含有油酸乙酯和乙酸的 IBCA 基栓塞组合物具有适中的粘度和降低的导管粘附性(≈0.80N),并且其聚合时间可自由控制在 2 至 15 秒之间。在兔模型的栓塞试验中,IBCA 基栓塞组合物成功闭塞了肾动脉,4 周内没有血管再通或非靶栓塞。在猪模型中进一步评估了它们的栓塞效果,证明了它们在临床上的实际应用。总之,IBCA 及其组合物有望成为新型液体栓塞剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8bb/11582500/b5d97cdb6afc/ADHM-13-0-g003.jpg

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