KR-102961555-B1 - An extracorporeal hemopurification device for scavenging reactive oxygen species

Abstract

This specification discloses an in vitro blood purification device and an in vitro blood purification method using the same. In one aspect, the present invention can effectively remove reactive oxygen species (ROS), which are inflammation-inducing substances in the blood, in vitro through porous micro beads loaded with ceria nanoparticles. Specifically, an in vitro blood purification device manufactured to allow perfusion of a patient's blood by loading the porous micro beads onto a blood perfusion cartridge can extensively and rapidly remove reactive oxygen species under aqueous solution and blood conditions. Accordingly, the present invention can be applied to a micro bead-based in vitro blood perfusion therapy system.

Inventors

• 정한길
• 김재윤
• 임필선
• 김동희

Assignees

• 주식회사 이터녹스

Dates

Publication Date

20260507

Application Date

20240119

Priority Date

20230119

Claims (15)

1. An in vitro blood perfusion cartridge comprising porous micro beads with a diameter greater than 10 μm and less than or equal to 1500 μm, on which ceria nanoparticles are attached to the surface.
2. In paragraph 1, The above porous micro beads are an in vitro blood perfusion cartridge that removes reactive oxygen species through the catalytic action of ceria nanoparticles.
3. delete
4. In paragraph 1, An in vitro blood perfusion cartridge having a pore volume of the porous microbeads of the above-mentioned amounting to 0.1 cm³ /g to 13.6 cm³ /g.
5. In paragraph 1, An in vitro blood perfusion cartridge having a surface area of 100 m² /g to 1,000 m² /g of the porous microbeads.
6. In paragraph 1, The above porous micro beads are an in vitro blood perfusion cartridge containing 3 mg/g or more of ceria nanoparticles.
7. In paragraph 1, An in vitro blood perfusion cartridge, wherein the porous micro beads are one or more selected from the group consisting of porous micro beads coated with alginate, porous micro beads coated with PEG (polyethylene glycol), porous micro beads coated with PVP (polyvinylpyrrolidone), and combinations thereof.
8. In Paragraph 7, The above porous micro beads are porous micro beads coated with PVP (polyvinylpyrrolidone), in vitro blood perfusion cartridge.
9. delete
10. In paragraph 1, The above porous micro beads have a volume ratio of 50% to 90% of the total in vitro blood perfusion cartridge.
11. An in vitro blood purification device comprising an in vitro blood perfusion cartridge according to any one of claims 1, 2, 4 through 8 and 10.
12. delete
13. A method for manufacturing porous micro beads for in vitro blood perfusion according to any one of claims 1, 2, 4 through 8 and 10, comprising the following steps: (a) a step of synthesizing porous microbeads and modifying their surface; and (b) A step of attaching ceria nanoparticles to the surface of the modified porous microbeads.
14. In Paragraph 13, The above step (a) is a method of modifying the surface of porous micro beads using a formulation comprising one or more functional groups selected from the group consisting of amine, thiol, and carboxylic groups.
15. In Paragraph 13, The above method further comprises the step of (c) coating a polymer on the surface of porous microbeads to which ceria nanoparticles are attached.

Description

An extracorporeal hemopurification device for scavenging reactive oxygen species The present specification discloses an in vitro blood purification device and an in vitro blood purification method using the same. Meanwhile, this application was supported by the following research and development project. [Research and development projects that supported this invention] [Project ID] 2022R1C1C100961012 [Ministry Name] Ministry of Science and ICT [Specialized Management Agency] National Research Foundation of Korea [Project Name] Basic Research Program in Science and Engineering > Support Program for Young Researchers > Excellent Young Researchers [Project Title] Development of a Multifunctional Microbead-Based In Vitro Blood Purification System for Sepsis Treatment [Contribution Rate] 60/100 [Organizing Institution] Seoul National University Bundang Hospital [Research Period] 2022.03.01 ~ 2025.02.28 [Project ID] RS-2023-00222910 [Ministry Name] Ministry of Science and ICT [Specialized Management Agency] National Research Foundation of Korea [Project Name] Bio and Medical Technology Development (R&D) [Project Title] Development of Clinically Applicable Technologies for Five Major Diseases and Fostering Physician-Scientists through the Personalized Future Medical Research Center for the 6P Medicine Era [Contribution Rate] 35/100 [Organizing Institution] Seoul National University Bundang Hospital [Research Period] April 1, 2023 ~ December 31, 2026 [Project ID] 13-2021-0004 [Department Name] Bundang Seoul National University Hospital [Specialized Management Agency] Bundang Seoul National University Hospital [Project Name] Joint Research in Key Support Areas [Project Title] Development of a Nanomaterial-Based Extracorporeal Blood Purification Device for the Treatment of Cytokine Storm [Contribution Rate] 5/100 [Organizing Institution] Seoul National University Bundang Hospital [Research Period] 2021.03.01 ~ 2024.03.01 Sepsis is essentially a severe infectious condition accompanied by a systemic inflammatory response. Due to the body's excessive and misguided reaction to infection, sepsis can cause tissue damage and organ dysfunction, potentially progressing to a life-threatening state. Systemic inflammatory response syndrome (SIRS) is a systemic inflammatory response exhibited by the body in response to various forms of severe stress or injury, such as infection, trauma, burns, and pancreatitis, and it plays a significant pathophysiological role in sepsis. To date, various drugs have been developed and undergone clinical trials for the treatment of sepsis, but they have failed to demonstrate efficacy. As a new approach to treating sepsis, blood purification therapies designed to remove pathogen-associated substances or cytokines from the body (e.g., Toraymyxin, Cytosorb) were developed and garnered attention; however, despite undergoing clinical trials, they were unsuccessful, and clinical guidelines currently do not recommend their use. Reactive oxygen species (ROS) are a critical factor in SIRS, including sepsis, where excessive production or insufficient removal damages cells, promotes inflammation, and triggers tissue damage and organ dysfunction. However, existing blood purification treatments have a clear limitation in that they cannot effectively remove free radicals. delete Figure 1 is a schematic diagram of a microbead-based blood perfusion system for removing reactive oxygen species in a sepsis model. Figure 2 relates to a process for manufacturing porous silica micro beads. Figure 3 is a representative image of each step of the preparation of porous silica microbeads from porous silica particles/alginate microbeads. Figure 4 shows the nitrogen ( N₂ ) physisisorption isotherms and pore diameter (red: 1 wt %, green: 3 wt %, blue: 5 wt%) of the final product, porous silica micro beads, according to the content (wt%) of the porous silica particles during the production of the initial porous silica particles/alginate micro beads. Figure 5 relates to a process for producing ceria nanoparticles/porous silica microbeads by attaching ceria nanoparticles to the surface of porous silica microbeads through electrostatic attraction. Figure 6 relates to the surface charge (zeta-potential) of porous silica particles and ceria nanoparticles. Figure 7 is a representative photographic image of porous silica micro beads and ceria nanoparticles/porous silica micro beads with ceria nanoparticles attached. Figure 8 relates to SEM images of porous silica micro beads and ceria nanoparticles/porous silica micro beads and an analysis of the distribution of cerium (Ce) atoms on the micro bead surface by EDS. Figure 9 is a schematic diagram of ceria nanoparticles/porous silica microbeads coated with PVP on the surface. Figure 10 shows the thermogravimetric analysis (TGA) results of porous silica micro beads, ceria nanoparticles/porous silica micro beads, and PVP-coated ceria nanoparticles/porous silica micro beads. Figure 11 relat