Synthetic Substitutes of Surgical Gut Sutures

描述(申请人提供)：第一阶段研究的目的是开发合成聚酯单丝缝合线作为外科肠道缝合线(SGS)的替代品，在初始机械性能、强度保持曲线和组织反应性方面具有更好的性能，并确实证明了开发合成聚酯单丝缝合线的可行性。阶段I结果表明：(1)多轴无定形聚合物引发剂可以与乙交酯末端接枝，生成晶态纤维状嵌段共聚酯(SP)；(2)两种基于SP的单丝被确定为可在第二阶段进一步开发的候选单丝。虽然这些单丝的柔度比干SGS高，但它们的硬度比湿SGS高。因此，对其他多轴纤维成形组合物进行了第一阶段后的研究，这些组合物可用于制备模数小于100kPSI的顺应性单丝，同时在其他缝合性能方面保持与SGS的竞争力。而链段多轴接枝聚酯(SPGS)的链由几乎无定形的聚三亚甲基碳酸酯核和主要基于乙交酯和e-己内酯的高链段可结晶末端组分组成，已被探索并被证明具有比SPS更有前途的性能。因此，修订了第二阶段的目标，将重点放在SPG系统的开发上，主要是生产符合要求的单丝缝合线，作为普通SGS和铬SGS的首选替代品。第二阶段计划包括：(1)优化在第一阶段后选择的两个SPG系统，以选择一个最终系统来生产普通SGS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系统的选定缝合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、稳定性和放大研究；(5)完成作为某些可吸收商业单丝的首选替代品的其他SPS和/或SPG的探索性研究；以及(6)完成第三阶段计划。

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.