Gel-forming Systems for Adhesion Prevention

描述（由申请人提供）： 针对最小化或预防术后粘连（POA）的I期研究表明：（1）无药物的凝胶形成赋形剂比透明质酸（HA）更有效;（2）基于HA的制剂通常不如它们的非水性凝胶形成赋形剂有效;（3）抗血管生成肽，特别是生长抑素类似物（醋酸兰瑞肽，LN）在形成凝胶的媒介物中对POA的预防比任何其它所检测的单独生物活性剂有效得多;和（4）某些抗炎药，特别是萘普生钠（NP）具有有希望的抗粘连特性。II期的目标是（1）选择最佳的凝胶形成载体，用于控制释放最佳有效剂量的NP和/或LN;（2）完成所选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II 1期抗粘连产品的商业化计划。因此，II期计划需要（1）使用大鼠侧壁模型（RT-SWM）并选择一个模型用于测试用于控制释放萘普生钠（NP）和/或LN的载体，优化非水双组分凝胶形成剂（GF）的组成和体积，以使其自身最小化POA的能力最大化;（2）使用RT-SWM优化所选GF组合物中NP和LN的浓度，以实现对POA预防的最大功效;（3）使用RT-SWM确定GF中NP和LN的所选组合的功效;（4）使用RT-SWM和兔侧壁模型（RB-SWM）进行优化的NP、LN和NP + LN制剂的比较研究，并选择一个系统用于完成使用猪侧壁模型（PG-SWM）的研究，以根据监管批准的需要启动额外的研究;以及（5）完成所选GF及其所选配方的开发和放大研究。

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.