Development of hemostatic glue and devices for use in endoscopic surgery.

开发用于内窥镜手术的止血胶和装置。

• 批准号: 07557358
• 负责人: NAKAYAMA Yasuhide
• 金额: $ 1.79万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557358/
• 关键词: Adhesive; Gelatin; Photoreaction; Hemostasis; Endoscopy; 止血剤; エキシマレーザー; ベンゾフェノン; 色素; 組織接着剤; エキシマ・レーザー

This research presents a novel photochemically-driven surgical tissue adhesive technology using photoreactive gelatins, which were partially derivatized with photoreactive groups, such as ultraviolet light (UV)-reactive benzophenone and visible light-reactive xanthene dye (e.g. fluorescein sodium salt, cosin Y,and rose bengal), anda water-soluble difunctional macromer [poly (ethylene glycol) diacrylate : PEGDA]. a series of photocurable tissue adhesive glues, which are viscous solutions when warmed, consisting of the photoreactive gelatin, PEDA, anda saline solution with or without ascorbic acidas a reducing agent, were prepared and evaluated for their effectiveness on hemostasis and anastomosis in cardiovascular surgery. Regardless of the type of photoreactive group examined, irradiation of the photocurable tissue adhesive glues by UV or visible light within 1 min, without excess heating, produced water-swollen gels, which had high adhesive strength to wet collagen film, due to the sy … More nergistic antion of photoreactive group-initiated photocrosslinking and photograft polymerization. As irradiation time increased, get yield increased and its ability to hold water decreased. a decrease in the molecular weight of PEGDA and an increase in concentration of both photoreactive gelatin and PEGDA resulted in a reduced ability to hold water and increased the tensile and burst strengths of the resultant gels. In rats in which the livers had been injured with a trephine during laparotomy, the bleeding spots were coated with the photocurable adhesive glue. Upon photoirradiation through an optical fiber, the coated solution was immediately converted to a swollen gel, which tightly adhered to the liver tissue, presumably by interpenetration and, concomitantly, hemostasis was completed. The anastomosis treatment with a photocurable adhesive glue in canine abdominal or thoracic aortas incised with a knife resulted in little bleeding under pulsatile flow after removing the clamps. Histological examination revealed that the adhesive glues photocured on rat liver surfaces gradually degraded in vivo with the infiltration of inflammatory cells and connectiv tissues, but without necrosis in the surrounding tissue. In addition, during laparoscopic surgery, percutaneous delivery of a photocurable adhesive glue and its in situ photogelation on rat liver surfaces was demonstrated using a specially designed fiberscope. These results suggest that the photocurable compound developed hear may serve as a biodegradable tissue adhesive glue for use in cardiovascular surgery and endoscopic surgery. Less

本研究提出了一种新型光化学驱动的外科组织粘胶技术，该技术使用光反应性明胶，该明胶部分衍生化与光反应基团，如紫外光（UV）反应性二苯甲酮和可见光反应性杂蒽染料（如荧光素钠盐，cosin Y和玫瑰红），以及水溶性双官能高分子[聚乙二醇二丙烯酸酯：PEGDA]。制备了一系列光固化组织胶粘剂，由光反应性明胶、PEDA和含或不含抗坏血酸还原剂的生理盐水溶液组成，加热后为粘性溶液，并评估了它们在心血管手术中的止血和吻合效果。无论检测的是哪种光反应基团，在不过度加热的情况下，用紫外线或可见光照射1分钟，产生水膨胀凝胶，由于光反应基团引发的光交联和光接枝聚合的更强的反作用力，水膨胀凝胶对湿胶原膜具有较高的粘附强度。随着辐照时间的延长，其产量增加，持水能力下降。PEGDA分子量的降低和光反应性明胶和PEGDA浓度的增加导致持水能力的降低，并增加了所得凝胶的拉伸和破裂强度。在开腹手术中肝脏被环钻损伤的大鼠，在出血点涂上光固化胶。经光纤光照射后，涂膜溶液立即转化为肿胀的凝胶，可能是通过互穿紧密粘附在肝组织上，同时完成止血。用光固化胶在犬腹主动脉或胸主动脉用刀切开吻合，取下夹钳后脉搏血流下出血少。组织学检查显示，光固化大鼠肝表面的胶粘剂在体内逐渐降解，炎症细胞和结缔组织浸润，但周围组织无坏死。此外，在腹腔镜手术中，使用特殊设计的纤维镜演示了经皮给药光固化胶及其在大鼠肝脏表面的原位光凝胶作用。这些结果表明，所开发的光固化化合物可作为可生物降解的组织胶用于心血管手术和内窥镜手术。少

项目成果

K.Ishibashi, Y.Nakayama, K.Kawazoe, T.Matsuda: "Development of a photocurable hemostatic agent-in situgelation by endoxcopic surgery" Jpn.J.Artif Organs. 24. 97-101 (1995)

K.Ishibashi、Y.Nakayama、K.Kawazoe、T.Matsuda：“内窥镜手术原位光固化止血剂的开发”Jpn.J.Artif Organs。

坂口泰久: "眼科領域における光硬化性組織接着剤の設計 第1報-光硬化性前嚢補強剤の開発-" 日本眼科紀要. 48. 463-471 (1997)

Yasuhisa Sakaguchi：“眼科领域光固化组织粘合剂的设计 - 第 1 部分 - 光固化前囊增强剂的开发”日本眼科通报 48. 463-471 (1997)。

Y.Nakayama, T.Matsuda: "Excimer laser-induced surface fixation of polymer and its patterning" J.Appl. Phys.80. 505-508 (1996)

Y.Nakayama、T.Matsuda：“准分子激光诱导聚合物表面固定及其图案” J.Appl。

中山 泰秀: "光架橋型ゼラチンの分子設計・エキシアレザー照射によるゲル化及び止血剤への応用" 人工臓器. 24. 102-105 (1995)

Yasuhide Nakayama：“光交联明胶的分子设计、Exia 激光照射的凝胶化以及作为止血剂的应用”人工器官。

Y.Nakyam: "Excimer laser-induced surface fixation of polymer and its pattering" J.of Applied Physics. 80. 505-508 (1996)

Y.Nakyam：“准分子激光诱导聚合物表面固定及其图案”应用物理学杂志。