Caterbi Sara, Buttarini Claudio, Garetto Stefano, Franco Moscardini Isabelle, Ughetto Stefano, Guerrini Angela, Panizzi Elena, Rumio Cristiano, Mattioli Laura, Perfumi Marina, Maidecchi Anna, Cossu Andrea, Bruley des Varannes Stanislas, Regula Jaroslaw, Malfertheiner Peter, Sardi Claudia, Lucci Jacopo
Bios-Therapy, Physiological Systems for Health S.p.A., Località Aboca 20, 52037 Sansepolcro, Italy.
Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, 20134 Milan, Italy.
Int J Mol Sci. 2025 Jan 29;26(3):1181. doi: 10.3390/ijms26031181.
When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of endoscopy-negative patients with heartburn and/or epigastric pain or burning. Here, we provide preclinical data describing the mechanism of action of the Poliprotect formulation, a 100% natural, biodegradable, and environmental friendly medical device according to EU 2017/745 and containing UVCB (unknown or variable composition, complex-reaction products, or biological materials) substances of botanical and mineral origin, according to the REACH and European Chemical Agency definitions. Different in vitro assays demonstrated the capability of Poliprotect to adhere to mucus-secreting gastric cells and concomitantly deliver a local barrier with buffering and antioxidant activity. In studies conducted in accordance with systems biology principles, we evaluated the effects of this barrier on human gastric cells exposed to acidic stress. Biological functions identified via Ingenuity Pathway Analysis highlighted the product's ability to create a microenvironment that supports the mucosal structural and functional integrity, promotes healing, and restores a balanced mucosal inflammatory status. Additionally, transepithelial electrical resistance and an Ussing chamber showed the product's capability of preserving the integrity of the gastric and esophageal epithelial barriers when exposed to an acid solution. Two in vivo models of erosive gastropathy further highlighted its topical protection against ethanol- and drug-induced mucosal injury. Overall, our findings sustain the feasibility of a paradigm shift in therapeutics R&D by depicting a very innovative and desirable mode of interaction with the human body based on the emerging biophysical, rather than the pharmacological properties of these therapeutic agents.
当胃食管黏膜的保护机制被损伤因素压倒时，黏膜的结构和功能完整性就会受到损害，从而导致一系列疾病。最近有研究表明，在治疗内镜检查阴性的烧心和/或上腹部疼痛或烧灼感患者时，Poliprotect并不逊色于标准剂量的奥美拉唑。在此，我们提供临床前数据，描述Poliprotect制剂的作用机制。根据欧盟2017/745标准，该制剂是一种100%天然、可生物降解且环保的医疗器械，根据REACH和欧洲化学品管理局的定义，其含有植物和矿物来源的UVCB（未知或可变组成、复杂反应产物或生物材料）物质。不同的体外试验表明，Poliprotect能够黏附于分泌黏液的胃细胞，并同时提供具有缓冲和抗氧化活性的局部屏障。在按照系统生物学原理进行的研究中，我们评估了这种屏障对暴露于酸性应激的人胃细胞的影响。通过Ingenuity Pathway Analysis鉴定的生物学功能突出了该产品创造微环境的能力，这种微环境可支持黏膜的结构和功能完整性、促进愈合并恢复平衡的黏膜炎症状态。此外，跨上皮电阻和尤斯灌流小室显示，该产品在暴露于酸性溶液时能够保持胃和食管上皮屏障的完整性。两种糜烂性胃病的体内模型进一步突出了其对乙醇和药物诱导的黏膜损伤的局部保护作用。总体而言，我们的研究结果通过描绘一种基于新兴生物物理特性而非这些治疗剂药理特性的、与人体非常创新且理想的相互作用模式，支持了治疗研发范式转变的可行性。
