Gel-forming Systems for Adhesion Prevention

用于预防粘附的凝胶形成系统

• 批准号: 6915686
• 负责人: SHALABY W SHALABY
• 金额: $ 35.76万
• 依托单位: POLY-MED, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915686
• 关键词: abdomen; adhesions; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biotechnology; cyclic peptides; disease /disorder prevention /control; drug vehicle; esters; gel; histology; interleukin 4; laboratory mouse; naproxen; packaging material; peptide hormone analog; postoperative complications; slow release drug; somatostatin; stomach surgery; swine

DESCRIPTION (provided by applicant): Phase I study directed toward minimizing or preventing post-operative adhesion (POA) demonstrated that (1) a drug-free, gel-forming copolyester vehicle is more effective than hyaluronic acid (HA); (2) HA-based formulations are generally less effective than their non-aqueous copolyester, gel-forming counterparts; (3) antiangiogenic peptide and, in particular, the somatostatin analog (lanreotide acetate, LN) in a copolyester gel-forming vehicle are much more effective toward POA prevention than any other individual bioactive agent examined; and (4) certain anti-inflammatory drugs, and particularly, naproxen sodium (NP) have promising anti-adhesion properties. Phase 2 objectives are to (1) select an optimum gel-forming copolyester vehicle for the controlled release of an optimized, effective dose of NP and/or LN; (2) complete the development and scale-up studies of a selected formulation; and (3) initiate the safety study in collaboration with a marketing partner and complete commercialization plans for an anti-adhesion product in Phase II1. Accordingly, Phase II plans entail (1) optimizing the composition and volume of the non-aqueous, two-component, gel-forming copolyester gel-former (GF) to maximize its own ability to minimize POA, using a rat sidewall model (RT-SWM) and selecting one for testing the vehicle for the controlled release of naproxen sodium (NP) and/or LN; (2) optimizing the concentration of NP and LN in the selected GF composition to achieve maximum efficacy toward POA prevention using a RT-SWM; (3) determining the efficacy of selected combinations of NP and LN in GF using a RT-SWM; (4) conducting comparative studies of optimized NP, LN, and NP + LN formulations using a RT-SWM and a rabbit sidewall model (RB-SWM) and selecting one system for completing a study using a pig sidewall model (PG-SWM) for initiating additional studies as needed for regulatory approval; and (5) completing development and scale-up studies of the selected GF and its selected formulation.

描述（由申请人提供）： 旨在减少或预防术后粘连 (POA) 的 I 期研究表明：(1) 无药物、凝胶形成的共聚酯载体比透明质酸 (HA) 更有效； (2) 基于 HA 的配方通常不如非水性共聚酯、凝胶形成配方有效； (3) 抗血管生成肽，特别是共聚酯凝胶形成载体中的生长抑素类似物（醋酸兰瑞肽，LN）对于预防 POA 比所检查的任何其他单独生物活性剂更有效； (4)某些抗炎药，特别是萘普生钠(NP)具有良好的抗粘连特性。第 2 阶段的目标是 (1) 选择最佳的凝胶形成共聚酯载体，以控制释放优化的有效剂量的 NP 和/或 LN； (2) 完成选定制剂的开发和放大研究； (3) 与营销合作伙伴合作启动安全性研究，并完成 II1 期抗粘连产品的商业化计划。因此，第二阶段计划需要（1）优化非水、双组分、凝胶形成共聚酯凝胶形成剂（GF）的成分和体积，以最大限度地提高其自身的能力，以最大限度地减少POA，使用大鼠侧壁模型（RT-SWM）并选择一种用于测试萘普生钠（NP）和/或LN控释的载体； (2) 使用 RT-SWM 优化所选 GF 组合物中 NP 和 LN 的浓度，以实现 POA 预防的最大功效； (3) 使用 RT-SWM 确定所选的 NP 和 LN 组合在 GF 中的功效； (4) 使用 RT-SWM 和兔侧壁模型 (RB-SWM) 对优化的 NP、LN 和 NP + LN 配方进行比较研究，并选择一个系统来使用猪侧壁模型 (PG-SWM) 完成研究，以便根据监管部门批准的需要启动其他研究； (5) 完成所选GF及其所选制剂的开发和放大研究。