T1 CONTRAST AGENT BASED ON ULTRATHIN IRON OXIDE NANOPARTICLES FOR MAGNETIC RESONANCE IMAGING Russian patent published in 2023 - IPC A61K49/18 B82Y5/00 B82Y25/00 B82Y30/00 B82Y40/00 

FIELD: pharmaceuticals.

SUBSTANCE: group of inventions relates to a T1 contrast agent for magnetic resonance imaging, containing cores of fine iron oxide nanoparticles having a diameter of 6 nm or less and a polydispersity index (PDI) of 0.2 or less, and micelles encapsulating core particles, moreover, micelles include a nonionic surface -active substance, consisting of a hydrophilic fragment containing at least two chains, and a hydrophobic fragment containing at least one hydrocarbon chain, also belongs to the platform for multiplex analyzes using the T1 contrast effect of magnetic resonance imaging, including the nuclei of fine oxide nanoparticles iron having a diameter of 6 nm or less and a polydispersity index (PDI) of 0.2 or less, and micelles encapsulating core particles, wherein a linker compound selected from the group ADIBO-PEG4-C18, ADIBO-PEG2000-DSPE is added to the surface of the cores, DBCO-PEG4-C18, DBCO-PEG2000-DSPE, DBCO-SA, N3-PEG4-C18 and N3-PEG2000-DSPE and micelles include a non-ionic coating chino-active substance, consisting of a hydrophilic fragment containing at least two chains, and a hydrophobic fragment containing at least one hydrocarbon chain, also relates to a method for obtaining nanoparticles for multiplex analyzes, including providing cores of fine iron oxide nanoparticles having a diameter of 6 nm or less and a polydispersity index (PDI) of 0.2 or less; modification of core particles with a linker compound selected from the group ADIBO-PEG4-C18, ADIBO-PEG2000-DSPE, DBCO-PEG4-C18, DBCO-PEG2000-DSPE, DBCO-SA, N3-PEG4-C18 and N3-PEG2000-DSPE, causing a click -reaction; providing a solution of micelles containing a nonionic surfactant, consisting of a hydrophilic fragment containing at least two chains, and a hydrophobic fragment containing at least one hydrocarbon chain; dispersion of the modified core particles in a micellar solution to impart hydrophilicity to the modified core particles by encapsulation with a ligand, which is an organic acid group C₄-C₂₅ ; and linking a functionalizing material containing a click reactive portion to the surface of the core particles to modify the surface of the core particles, and also relates to a method for producing nanoparticles for multiplex assays, including providing cores of fine iron oxide nanoparticles having a diameter of 6 nm or less and a polydispersity index (PDI) 0.2 or less; providing a solution of micelles in which a nonionic surfactant consisting of a hydrophilic moiety containing at least two chains and a hydrophobic moiety containing at least one hydrocarbon chain is mixed with an amphiphilic material containing a functionalizing group selected from the group consisting of disease-targeting agents, chelating agents, fluorescent materials, and mixtures thereof; and dispersing the core particles in the micellar solution, so that hydrophilization of the core particles is simultaneously performed by encapsulating the ligand, which is organic acid groups C₄-C₂₅; and modifying the surface of the core particles with the functionalizing material.

EFFECT: group of inventions provides ultrafine iron oxide nanoparticles obtained on the basis of a combination of the uniform core synthesis method and the surface hydrophilization method, and which have a uniform contrast effect, while maintaining their in vivo uniformity, which is thus suitable for use in obtaining contrast agents T1, which can replace conventional gadolinium-based contrast agents.

15 cl, 15 dwg, 3 tbl, 11 ex