Synthetic Substitutes of Surgical Gut Sutures

外科肠道缝合线的合成替代品

• 批准号: 7287423
• 负责人: SHALABY W SHALABY
• 金额: $ 39.14万
• 依托单位: POLY-MED, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-10-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7287423
• 关键词: Carbonates; Development; Dose; Ethylene Oxide; Evaluation; Fiber; In Vitro; Marketing; Mechanics; Operative Surgical Procedures; Phase; Phase I Clinical Trials; Phase III Clinical Trials; Polyesters; Process; Property; Radiation; Reliance; Safety; Sterilization for infection control; Surgical sutures; System; Technology; Tissues; Validation; base; caprolactone; carbene; comparative; copolymer; in vivo; polytrimethylene carbonate; radiochemical; scale up; validation studies

DESCRIPTION (provided by applicant): Phase I study was intended and did demonstrate feasibility of developing synthetic polyester monofilament sutures as alternatives to surgical gut sutures (SGS) with preferred properties in term of initial mechanical properties, strength retention profile, and tissue reactivity. Phase I results showed that (1) polyaxial amorphous polymeric initiators can be end-grafted with glycolide to produce crystalline fiber- forming segmented copolyesters (SP) and (2) two SP-based monofilaments were identified as candidates for further development in Phase II. Although the compliance of these monofilaments was higher compared to dry SGS, they were stiffer than wet SGS. Hence, post-Phase I studies were pursued on other polyaxial fiber-forming compositions which can be used to prepare compliant monofilaments with a modulus of less than 100 Kpsi while remaining competitive with SGS in terms of other suture properties. And segmented polyaxial grafted polyesters (SPGs) having chains made of practically amorphous polytrimethylene carbonate core and highly segmented crystallizable terminal components based principally on glycolide and e-caprolactone were explored and shown to have more promising properties than the SPs. Hence, Phase II objective was revised to focus on the development of the SPG system primarily to produce compliant monofilament sutures as preferred alternatives to plain and chromic SGS. And, Phase II plans entail (1) optimization of two SPG systems selected in post-Phase I to choose one final system to produce preferred alternatives to plain and chromic SGS, with and without reliance on significant radiation-dose modulation of their properties; (2) completion of development and process validation studies on selected sutures based on the final SPG system; (3) completion of comparative in vitro and in vivo studies of SGS and their synthetic SPG-based alternatives (SGS-A); (4) initiation of safety, stability, and scale-up studies on SGS-A; (5) completing exploratory studies on other SPs and/or SPGs as preferred alternatives to certain absorbable commercial monofilaments; and (6) completing Phase III plans.

描述（由申请方提供）：I期研究预期用于证明开发合成聚酯单股缝线作为外科肠线（SGS）替代品的可行性，在初始机械性能、强度保留特征和组织反应性方面具有首选性能。第一阶段的结果表明：（1）多轴无定形聚合物引发剂可以与乙交酯进行端接枝，以产生结晶纤维形成的嵌段共聚酯（SP）和（2）两种SP基单丝被确定为第二阶段进一步开发的候选者。尽管这些单丝的顺应性比干燥SGS高，但它们比湿SGS更硬。因此，对其他多轴向成纤组合物进行了I期后研究，这些组合物可用于制备模量小于100 Kpsi的顺应性单丝，同时在其他缝线性能方面与SGS保持竞争力。和嵌段多轴接枝聚酯（SPG）的链由几乎无定形的聚三亚甲基碳酸酯核心和高度分段结晶的终端组件主要基于乙交酯和ε-己内酯进行了探索，并显示出更有前途的性能比SP。因此，修订了II期目标，重点关注SPG系统的开发，主要用于生产顺应性单股缝线，作为普通和铬SGS的首选替代品。并且，第II阶段计划需要（1）优化第I阶段后选择的两种SPG系统，以选择一种最终系统来生产普通和铬SGS的首选替代品，无论是否依赖于其性能的显著辐射剂量调制;（2）完成基于最终SPG系统的选定缝线的开发和工艺验证研究;（3）完成SGS及其合成SPG替代品（SGS-A）的体外和体内比较研究;（4）启动SGS-A的安全性、稳定性和规模扩大研究;（5）完成其他SP和/或SPG作为某些可吸收商业单丝的首选替代品的探索性研究;（六）完成第三期规划。