ANTI-SCARRING AND ANTI-INFLAMMATORY EFFECTS OF AMNIOTIC MEMBRANE EXTRACTS

描述（由申请人提供）：由于Pi在过去十年的开创性工作，羊膜移植（AMT）用于眼表重建于2001年获得FDA批准，并于2004年由Medicare报销作为标准外科手术。许多研究表明，AMT在促进上皮伤口愈合和减少基质炎症、疤痕和不必要的新血管形成方面是有效的。使用Pi的专有方法，Bio-Tissue （TissueTech, Inc.的子公司）自1997年以来已向全球1,200多名眼科医生分发了10,000多件人类羊膜产品（商标名称：“AmnioGraftTM”）。然而，羊膜移植手术需要在手术室进行缝合和手术。此前，我们开发了一种“无缝线”羊膜移植，并获得了FDA的510(k)批准，作为II类设备（2003年），商标为ProkeraTM，这是我们实现无缝线AMT的最终目标的第一步，以降低医疗成本，方便患者护理，特别是对于那些患有严重眼表破坏的患者，如史蒂文斯约翰逊综合征和化学烧伤。在这个I期申请中，我们提供了初步的数据来支持验证AM提取物的水溶性和冻干粉抗疤痕和抗炎作用的可行性，基于我们新报道的TGF-b启动子活性和巨噬细胞凋亡的体外实验。因此，我们提出了另一种新的方法来提供AM固有的抗炎和抗疤痕作用，而不受羊膜移植或Prokera TM的片状结构的限制。我们想比较使用胶原蛋白或透明质酸作为载体来传递这两种不同AM提取物的相对效力（目的1），并确定在AM基质中观察到的大部分（如果不是全部）抗疤痕和抗炎作用的分子成分（目的2）。成功完成这两个目标将使我们能够在第二阶段收集临床前动物试验的关键数据。我们相信，这些新技术将产生新的治疗方法，将AM固有的抗疤痕和抗炎作用传递到任何身体部位，并有助于扩大我们的市场潜力，不仅在眼科，而且在其他医学和外科亚专科，只要抑制组织炎症和疤痕成为必要。

DESCRIPTION (provided by applicant): Due to the Pi's pioneering work over the past decade, amniotic membrane transplantation (AMT) for ocular surface reconstruction was approved by the FDA in 2001 and reimbursed by Medicare in 2004 as a standard surgical procedure. A number of studies have shown that AMT is effective in facilitating epithelial wound healing and reducing stromal inflammation, scarring and unwanted new blood vessel formation. Using the Pi's proprietary method, Bio-Tissue (a subsidiary of TissueTech, Inc.) has distributed more than 10,000 human amniotic membrane products (trademark name: "AmnioGraftTM") to more than 1,200 ophthalmic surgeons worldwide since 1997. Nevertheless, the AmnioGraft transplantation procedure requires the use of sutures and surgery in an operating room. Previously, we developed a "sutureless" AmnioGraft and received FDA's 510(k) approval for this as a Class II device (2003), trademarked as ProkeraTM, as a first step toward achieving our ultimate objective of performing AMT without sutures to reduce the medical cost and facilitate the ease of patient care, especially for those patients suffering from severe ocular surface destruction such as Stevens Johnson syndrome and chemical burns. In this Phase I application, we present preliminary data to support the feasibility of verifying anti-scarring and anti-inflammatory effects in both water-soluble and lyophilized powder of AM extracts based on our newly reported in vitro assays of TGF-b promoter activity and macrophage apoptosis, respectively. We thus, propose another novel approach of delivering AM's inherent anti-inflammatory and anti-scarring effects without being restricted by the sheet configuration of AmnioGraft or Prokera TM. We would like to compare the relative potency of using collagen or hyaluronic acid as a vehicle to deliver such effects of these 2 different AM extracts (Aim 1), and to identify the molecular component(s) that is responsible for most, if not all, anti-scarring and anti-inflammatory effects observed in AM stroma (Aim 2). Successful completion of these 2 aims will allow us to gather critical data for pre-clinical animal testing during the Phase II. We believe that these new technologies will generate new therapeutics to deliver AM's inherent anti-scarring and anti-inflammatory effects to any body site, and help expand our market potential not only in ophthalmology but also in other medical and surgical subspecialties whenever suppressing of tissue inflammation and scarring becomes necessary.