Water-based liquid embolic agent for the treatment of vascular rich tumors

用于治疗富含血管肿瘤的水基液体栓塞剂

• 批准号: 10766633
• 负责人: Ichiro Yuki
• 金额: $ 39.95万
• 依托单位: AQUATEX MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10766633
• 关键词: Adhesiveness; Adverse event; Angiography; Animal Experiments; Animals; Arterial Embolization; Blood; Blood Vessels; Calcium ion; Cancer Etiology; Catheters; Cell Culture Techniques; Cell Death; Cessation of life; Clinical; Collagen; Control Groups; Devices; Dimethyl Sulfoxide; Drug Delivery Systems; Evaluation; FDA approved; Fluoroscopy; Food Additives; Future; Goals; Hepatic artery; Histologic; Hydrogels; Hypervascular; Immunologics; International; Ischemia; Laboratories; Legal patent; Liquid substance; Liver neoplasms; Macrophage; Magnetic Resonance Imaging; Malignant Neoplasms; Marketing; Medical; Modeling; Monitor; Organic solvent product; Oryctolagus cuniculus; Patients; Penetration; Periodicals; Pharmaceutical Preparations; Phase; Polysaccharides; Primary carcinoma of the liver cells; Procedures; Property; Radioactive; Radiology Specialty; Recurrence; Research; Roentgen Rays; Safety; Sampling; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Solid; Step Tests; System; Technology; Testing; Therapeutic; Therapeutic Embolization; Time; Tissues; Toxic effect; Tumor Volume; Viscosity; Water; aqueous; artery occlusion; biomaterial compatibility; cancer therapy; chemotherapy; clinical practice; comparative efficacy; contrast enhanced; design; feeding; first-in-human; human study; improved; indexing; innovation; novel; novel therapeutics; particle; preclinical evaluation; recruit; research and development; research clinical testing; tumor; tumor growth

AquaTeX Medical is developing a novel liquid embolic material (LEM) - Aqua Embolic System (AES) - to improve cancer treatment. AES is designed to occlude feeding vessels of hypervascular tumors with superior efficacy and excellent biocompatibility as compared to other trans-arterial embolization (TAE) materials. TAE is a catheter-based treatment to treat hypervascular tumors. Embolic materials are injected via a small catheter placed in the artery occluding the vessels, causing cell death by ischemia. The need for TAE treatment is rapidly growing, and its market forecast is expected to reach $2.164 billion in 2025. Currently, microparticles are the most commonly used embolic materials for TAE. Despite their wide use, microparticles have their limitations, e.g.,1) sub-optimal tissue penetration due to clumping effects or the relatively large size of each particle, 2) incomplete occlusion of the treated vessel leading to high recanalization rate (16-64%), 3) lack of visibility under x-ray requiring the addition of contrast medium, and 4) inability to load many current chemotherapeutic drugs or immunologically active molecules. Therefore, there is a strong need for better embolic materials. LEMs, on the other hand, have 1) superior tissue penetration, 2) capability to achieve permanent occlusion of the target vessels, and 3) good visibility under fluoroscopy. However, the FDA has not yet approved any LEMs to treat hypervascular tumors, due to safety concerns related to the strong adhesiveness or tissue toxicity caused by the organic solvents in current LEMs on the market. To overcome these limitations, we have developed the first single-component water-based LEM called AES. AES is a clear aqueous solution composed of biocompatible polysaccharides. It is activated by the calcium ions in the blood and forms a solid hydrogel cast that shows excellent tissue penetration. With its unique viscosity- controlling technology, AES can be delivered via the currently available smallest single-lumen microcatheter system. It contains no toxic organic solvents, and moreover, the main compositions of the AES have been widely used for cell culture medium and food additives with FDA approval. Our preliminary animal experiments showed consistent efficacy and biocompatibility of the AES. The primary goal of this Phase I STTR project is 1) to confirm the efficacy of the AES using a rabbit hypervascular tumor model, which has been historically used for preclinical evaluation of embolic materials for FDA approval, and 2) to evaluate long-term safety, durability, and biocompatibility using a non-tumor hepatic artery embolization model. Embozene®, which is a micro-particle product currently used in the clinical practice, is used as comparison (commercial control). In our subsequent Phase II SBIR/STTR project, we will pursue the next step of testing needed for investigational device exemption (IDE) approval, followed by the first-in-human study. Our final goal is to improve the safety and efficacy of TAE procedures performed for patients with hypervascular tumors.

AquaTeX Medical正在开发一种新型液体栓塞材料（LEM）- Aqua栓塞系统（AES）， 改善癌症治疗。AES用于闭塞富血供肿瘤的供血血管，具有上级 与其他经动脉栓塞（TAE）材料相比，其有效性和优异的生物相容性。 TAE是一种基于导管的治疗方法，用于治疗多血管肿瘤。栓塞材料通过一个小的 放置在动脉中的导管阻塞血管，导致细胞因局部缺血而死亡。需要TAE治疗 正在快速增长，其市场预测预计将在2025年达到21.64亿美元。目前，微粒子 是TAE最常用的栓塞材料。尽管它们被广泛使用，但微粒具有其 限制，例如，1)由于结块效应或每个的相对大的尺寸， 颗粒，2）治疗血管的不完全闭塞导致再通率高（16-64%），3）缺乏 在X射线下的可见性需要添加造影剂，以及4）不能加载许多电流 化疗药物或免疫活性分子。因此，迫切需要更好的 栓塞材料。另一方面，LEM具有1）上级组织穿透性，2）实现 靶血管的永久性闭塞，以及3）在荧光透视下的良好可见性。然而，FDA没有 但由于与强血管生成相关的安全性问题， 或由目前市场上LEM中的有机溶剂引起的组织毒性。 为了克服这些限制，我们开发了第一个单组分水基LEM，称为AES。 AES是由生物相容性多糖组成的澄清水溶液。它被钙离子激活 并形成显示出优异的组织渗透性的固体水凝胶铸件。以其独特的粘度- 控制技术，AES可以通过目前可用的最小单腔微导管输送 系统它不含有毒有机溶剂，而且AES的主要成分已被广泛应用， 用于细胞培养基和FDA批准的食品添加剂。我们初步的动物实验表明 AES的一致功效和生物相容性。 第一阶段STTR项目的主要目标是：1）使用兔子确认AES的有效性 多血管肿瘤模型，历史上曾用于栓塞材料的临床前评价， FDA批准，以及2）使用非肿瘤肝细胞评价长期安全性、耐久性和生物相容性 动脉栓塞模型Embozene®是一种目前用于临床实践的微粒产品， 用作比较（商业对照）。 在我们随后的第二阶段SBIR/STTR项目中，我们将继续进行研究所需的下一步测试。 器械豁免（IDE）批准，随后是首次人体研究。我们的最终目标是提高 和对富血管肿瘤患者进行TAE手术的有效性。