Synthetic Substitutes of Surgical Gut Sutures

描述（由申请人提供）：I期研究旨在并且确实证明了开发合成聚酯单丝缝合线作为外科肠缝合线（SGS）的替代品的可行性，该缝合线在初始机械性能、强度保持轮廓和组织反应性方面具有首选性能。第一阶段的研究结果表明：(1)多轴非晶聚合物引发剂可以末端接枝乙醇酸，生成结晶纤维形成的节段共聚酯（SP）；(2)两种基于SP的单丝被确定为第二阶段进一步发展的候选材料。虽然这些单丝的顺应性比干燥的SGS更高，但它们比湿的SGS更硬。因此，在I期后的研究中，研究人员对其他多轴纤维形成成分进行了研究，这些成分可用于制备弹性单丝，其模量小于100 Kpsi，同时在其他缝合性能方面与SGS保持竞争。此外，研究人员还发现了一种分段多轴接枝聚酯（SPGs），其链由几乎无定形的聚三甲基碳酸酯核心组成，末端组分主要由乙醇酸酯和e-己内酯组成，具有高度分段结晶性，并显示出比SPs更有前景的性能。因此，第二阶段的目标被修改为专注于SPG系统的开发，主要是为了生产符合要求的单丝缝合线，作为普通和无色SGS的首选替代品。第二阶段计划包括：(1)优化第一阶段后选择的两种SPG系统，选择一种最终系统来生产普通和无色SGS的首选替代品，无论是否依赖于其特性的显著辐射剂量调制；(2)完成基于最终SPG系统的选定缝合线的开发和工艺验证研究；(3)完成SGS及其基于spg的合成替代品（SGS- a）的体外和体内比较研究；(4)启动SGS-A的安全性、稳定性和规模化研究；(5)完成其他SPs和/或SPs作为某些可吸收的商业单丝的首选替代品的探索性研究；(6)完成三期规划。

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.