Novel triazine-based detoxification agents and their use

Abstract

An affinity ligand-matrix conjugate comprises the matrix and conjugated thereto by the group Z, a ligand having general formula (I): wherein one X is N and the other X is N, CCL or CCn; A1 and A2 are each independently O, S or N—R1 and R1 is H, C1-6 alkyl, C1-6 hydroxyalkyl, benzyl or β-phenylethyl; B1 and B2 are each independently an optionally substituted hydrocarbon linkage containing from 1 to 10 carbon atoms; D1 is H or a primary amino, secondary amino, tertiary amino, quaternary ammonium, imidazole, guanidine or amidino group; and D2 is a secondary amino, tertiary amino, quaternary ammonium, imadazole, guanidine or amidino group; or B2-D2 is —CHCOOH—(CH2)3-4—NH2; and p is 0 or 1. Such conjugates are useful for the separation, isolation, purification, characterization, identification or quantification of an endotoxin.

Description

FIELD OF THE INVENTION The present invention relates to novel affinity ligands, their preparation and attachment to matrices which may consist of solid, semi-solid, particulate or colloidal materials, or soluble polymers. The invention furthermore relates to these novel affinity ligand-matrix conjugates and the preparation and use thereof in the binding and removal of endotoxin from various fluids such as water, aqueous solutions, body fluids, blood, plasma, solutions of pharmaceutical products, proteins and other compounds of biological origin. BACKGROUND OF THE INVENTION Endotoxins are lipopolysaccharides found in the outermost membrane of Gram-negative bacteria, particularly pathogeneic bacteria of the class Enterobacteriaceae, Neisseriaceae and Chlamydiaceae. Endotoxins comprise lipid A attached to a polysaccharide of variable structure dependent upon its biological origin. The polysaccharide component of Enterobacteriaceae endotoxin is characterised by an O-specific chain reg...

AI Technical Summary

Benefits of technology

A feature of the present invention is the provision of a general tool for the removal of endotoxin contamination from biological materials. Endotoxin binds exceedingly tightly to affinity ligand-matrix conjugates of the invention. This feature enables highly efficient extraction of endotoxin from water and aqueous solutions providing a means of generating pyrogen-free water or pyrogen-free solutions. Affinity ligand-matrix conjugates of the invention are especially valuable for the removal of endotoxin which is bound to or associated with proteins, drugs or other biological compounds intended for medical or pharmaceutical applications. Certain biological compounds, particularly proteins, often bind endotoxin tightly and subsequent removal is very difficult, if not impossible, by existing means. Affinity ligand-matrix conjugates of the invention may also be applied to the removal of endotoxin from blood or plasma and so provide an especially useful tool for in vitro or in vivo removal of endotoxin, the latter being achieved, for example, by way of an extracorporeal endotoxin extraction device. Such a device may be especially valuable for removal of endotoxin which is released into the blood stream during bacterial infections, such infections often causing life-threatening diseases such as septicaemia or meningitis. Removal of blood-borne endotoxin may be particularly beneficial in the treatment of these diseases and in the prevention and management of septic shock.

Novel affinity ligand-matrix conjugates provided by this invention can be used in place of other endotoxin binding materials and are significantly more flexible in their use, are more robust, less expensive to produce and offer greater endotoxin binding efficiencies.

Problems solved by technology

Certain biological compounds, particularly proteins, often bind endotoxin tightly and subsequent removal is very difficult, if not impossible, by existing means.

Images