Patent ID: 9585987
Date: 2017-03-07
CPC Classifications: A61K,A61L,A61P,C08B,C08F,C08J,C08L

Claim:
1. A composition which upon activation spontaneously forms a cross-linked hydrogel in an aqueous liquid, said composition comprising: a) a first formulation comprising a functionalized hyaluronan (HA) comprising an HA-backbone and a plurality of HA-reactive substituent groups directly attached to said HA-backbone, said substituent group comprising a reactive functional HA-group, wherein the degree of substitution (DS) measured as number of reactive HA-substituents per repeating unit is ≦20%, and b) a second formulation comprising a homo-multifunctional cross-linking reagent of a polyhydroxy polymer (PHP) comprising a PHP-backbone and a plurality of PHP-reactive substituent groups attached to said PHP-backbone, said substituent group comprising one or more reactive functional PHP-groups, wherein said PHP-backbone comprises one or more linear structures selected from the group consisting of: (i) linear polyamide backbones of identical or different monomeric subunits linked together one after the other with an amide bond (—CONR′ (ii) linear polyester backbones of identical or different monomeric subunits with an ester bond (—COO—) linking two neighboring subunits together, and with corresponding monomers selected from hydroxy carboxylic acids or combinations of a dialcohol with a dicarboxylic acid; (iii) linear polyether backbones of identical or different monomeric alkylene oxide subunits with an ether bond (—O—) linking two neighboring subunits together and a straight alkylene chain linking neighboring ether groups together, with the proviso that the chain comprises ≧2 carbons, and with corresponding monomers selected from alkylene oxides; and (iv) linear polyvinyl backbones of identical or different monomeric C said reactive HA and PHP groups being selected as a pair of counterparts that are capable of mutually and selectively reacting with each other to form a covalent linkage structure, A) a first counterpart of said pair comprises a nucleophilic group and a second counterpart of the same pair comprises an electrophilic group, said nucleophilic groups being selected from the group consisting of: carbazate groups, hydrazide groups, semicarbazide groups, thiosemicarbazide groups, aminooxy groups, thiol groups, and β-aminothiol groups, and said electrophilic groups being selected from the group consisting of: aldehyde groups, maleimide groups, acrylate groups, acrylamide groups, methacrylate groups, methacrylamide groups, vinylsulphone groups, and aziridinyl groups, or B) the two counterpart groups of said pair are counterpart reactants capable of reacting with each other in a cycloaddition reaction, and wherein said hydrogel has a cross-linking structure which is attached to said hyaluronan via two or more of said linkage structure and defined by said cross-linking reagent, and wherein said cross-linking structure exhibits a plurality of hydroxyl groups.