METHOD OF PRODUCING CONJUGATED HYDROGELS BASED ON POLY-N-ISOPROPYLACRYLAMIDE, SOLUBLE FRACTION OF GLYCOPROTEINS AND GLYCOSAMINOGLYCANS OF ENDOMETRIAL EXTRACELLULAR MATRIX AND PLATELET LYSATE Russian patent published in 2023 - IPC A61L27/36 A61L27/44 A61L27/50 A61L27/52 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a method of producing a conjugated hydrogel based on poly-N-isopropylacrylamide, a soluble fraction of glycoproteins and glycosaminoglycans of the endometrial extracellular matrix (eECM) and platelet lysate (PL), including, in fact, the synthesis of poly-N-isopropylacrylamide and its conjugation with biologically active components and characterized by the following: it is carried out in two stages: - synthesis of poly-N-isopropylacrylamide (PNIPAAm), including radical polymerization of N-isopropylacrylamide in deionized water (DW) with a resistance of 18 megaohms, using potassium persulfate (PSC) as an initiator and sodium meta-bisulfite as a redox initiator and co-initiator, respectively, for which N-isopropylacrylamide (NIPAAm) is dissolved in DV at a concentration of 5 wt.%, placed in a reactor and degassed in an ultrasonic bath for 2–3 minutes, then the polymerization initiator PSA and sodium metabisulfite are added to the system at a concentration of 0.05 wt.% of each, the reaction mixture is bubbled for 5 minutes in the reactor with argon to remove residual oxygen and polymerize at 20°C for 8 hours with intensive stirring at a speed of 350–400 rpm using an overhead mixer; - preparation of conjugated hydrogels based on PNIPAAm, eVCM and TL, including the addition of PNIPAAm at 0.05÷0.2% solution of glutaraldehyde in 0.1 M phosphate buffer to a concentration of 2 wt.%, eVCM 0.2 wt.% and TL 0.1 wt.%, bubbling the reaction mixture in the reactor with argon to remove residual oxygen for 3–5 minutes and vigorous stirring at 37± 1° C for 8 hours at a speed of 500–600 rpm. The invention provides the creation of a thermosensitive system, including agents that imitate the main regulatory properties of eECM for cellular elements in contact with it, in addition, having additionally increased biological activity due to TL growth factors (GFs), activating regeneration, and the gel itself should represent is a sol with low viscosity, when it enters the uterine cavity under the influence of body temperature due to a sharp increase in dynamic viscosity when the lower critical temperature of the solution is exceeded (LCST), it immediately hardens in areas of contact with warm walls with good adhesion to the warm surface.

EFFECT: method of producing conjugated hydrogels based on poly-N-isopropylacrylamide, a soluble fraction of glycoproteins and glycosaminoglycans of the endometrial extracellular matrix and platelet lysate.

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