Method to produce hyaluronic acid functionalized derivatives and formation of hydrogels thereof

摘要

In this invention a two steps procedure is described useful to insert functional groups to the hyaluronic acid (HA), through the formation, in organic solvent, of a particular active group on hydroxyl groups of HA and subsequent substitution, on the inserted active group, with a pendant portion containing at least in its terminal portion a nucleophilic functional group, NH2—R. The group inserted by nucleophilic substitution can contain in another its terminal portion a further nucleophilic functional group, in a way to be easily exploitable to further chemical functionalizations, such as an example to obtain the methacrylation of HA functional groups, to obtain photocrosslinkable derivatives. Both direct derivatives of the proposed process and those obtained by the further functionalization can be employed to produce hydrogels.

主权项

1. A process for producing functionalized derivatives of hyaluronic acid having a molecular weight in the range of 50,000 to 1,500,000 dalton comprising the following subsequent steps:
a) activation of at least one hydroxyl group of hyaluronic acid, in the form of a salt thereof soluble in organic solvents, by reaction of the said hyaluronic acid salt, in a polar aprotic solvent, with a carbonilating agent selected from carbonic phenyl esters and haloformic phenyl esters; b) reaction of the activated hyaluronic acid salt resulting from step a), through a nucleophilic substitution reaction with a compound of the general formula NH2-R, wherein R is selected from the group consisting of NH2, an amino alkyl group, an alkyl or an arylalkyl chain, a polyacrylic chain, a polyoxyethylene chain or a molecule of low molecular weight (as example a drug) or a high molecular weight molecule.