FIELD: medicine.
SUBSTANCE: present invention relates to the field of medicine, namely to a method for the production of hydrogels consisting of cross-linked glycosaminoglycans, which includes: a) reaction of an aqueous solution of at least one hybrid cooperative complex of the first component selected from hyaluronic acid with low molecular weight, chondroitin, and chondroitin sulfate, and the second component consisting of hyaluronic acid with high molecular weight with diepoxide as a cross-linking agent in the ratio with the complex from 0.1 to 1 equivalent; at the same time, the weight concentration of the complex in the solution is in the range from 1% to 15%; b) purification by dialysis, ultrafiltration, and diafiltration; moreover: the hybrid cooperative complex is obtained by subjecting the aqueous solution of the mixture of the mentioned first and second components to heat treatment at 80-160°C during time in the range from 10 to 30 minutes with subsequent cooling to 20-25°C during time in the range from 5 to 15 minutes; the weight concentration of the first component with low molecular weight is in the range from 0.1 to 50%, and the weight concentration of the second component with high molecular weight is in the range from 0.01 to 10%. At the same time, the molecular weight of hyaluronic acid with low molecular weight is in the range from 50·103 Da to 900·103 Da, the molecular weight of chondroitin or chondroitin sulfate is in the range from 5000 to 150,000 Da, and the molecular weight of hyaluronic acid with high molecular weight is in the range from 1·106 Da to 3·106 Da, where the molecular weight is Mw obtained by size exclusion chromatography SEC and/or size exclusion chromatography with a triple detector array SEC-TDA.
EFFECT: present invention provides for an increase in the stability of a three-dimensional cross-linked structure after cross-linking, which guarantees better and more long-lasting rheological properties.
9 cl, 3 ex
Authors
Dates
2022-08-17—Published
2018-11-14—Filed