Hyaluronic acid-protein conjugates and method for preparing same

摘要

An HA-protein conjugate in which an HA-aldehyde derivative, in which an aldehyde group is introduced to a hyaluronic acid or a salt thereof, is conjugated to the N-terminus of a protein, and a method for preparing the same are provided. The HA-protein conjugate includes a protein drug exhibiting an excellent bioconjugation efficiency and long-term medicinal effects, and has excellent protein drug activities since the hyaluronic acid is specifically conjugated to the N-terminus of the protein. Also, since liver-targeting properties of the hyaluronic acid can be freely controlled by changing an aldehyde substitution rate of the HA-aldehyde derivative, the HA-protein conjugate can be effectively used as a protein drug for treating liver diseases, and also be useful in enabling long-term medicinal effects of a protein drug required to bypass the liver. Accordingly, the HA-protein conjugate can be effectively used for a drug delivery system of proteins.

主权项

1. A method for preparing a hyaluronic acid (HA)-protein conjugate, comprising:
allowing an HA-aldehyde derivative in which at least one aldehyde group is introduced into the glucuronic acid backbone of hyaluronic acid or a salt thereof to react with an N-terminus of a protein to thereby obtain the HA-protein conjugate, wherein the protein is selected from the group consisting of interferon alpha (IFNα), interferon beta (IFNβ), interferon gamma (IFNγ), and a tumor necrosis factor (TNF), and wherein the HA-aldehyde derivative has an aldehyde substitution rate of 5% or more and less than 30%, such that the HA-protein conjugate has a longer half-life than the protein.