Fractionation of Charged Polysaccharide

摘要

Polydisperse and charged polysaccharides are fractionated into low polydispersity fractions (preferably having pd<1.1), each containing species within a narrow range of molecular weights. An aqueous solution of the polydisperse polysaccharides is contacted with an ion exchange resin in a column and the polysaccharides are subjected to selective elution by aqueous elution buffer. The selective elution consists of at least 3 sequential elution buffers having different and constant ionic strength and/or pH and in which the subsequent buffers have ionic strength and/or pH than those of the preceding step. The new preparations are particularly suitable for the production of PSA-derivatised therapeutic agents intended for use in humans and animals.

主权项

1. A process for separating a population of polydisperse polysialic acid compounds into fractions of different molecular weight and narrow polydispersity, the process comprising the steps of:
sequentially applying at least three elution buffers to an ion-exchange column previously contacted with a solution comprising the population of polydisperse polysialic acid compounds, the application of each of the at least three elution buffers resulting in a selective elution of a fraction of polysialic acid compounds, thereby separating the population of polydisperse polysialic acid compounds into fractions of different molecular weight and narrow polydispersity, wherein each of the fractions comprise polysialic acid compounds having at least 10 sialic acid units and a polydispersity of less than 1.2, wherein the at least three elution buffers include a first elution buffer, a second elution buffer and a third elution buffer, and wherein the second elution buffer has a higher pH than the first elution buffer and the third elution buffer has a higher pH than the second elution buffer.