Nasal formulations of low sialic acid recombinant human erythropoietin (rhuepo) for the treatment of central nervous system diseases

摘要

Nasal formulations of low sialic acid recombinant human erythropoietin (rHuEPO) for the treatment of central nervous system disorders. The present invention relates to the biopharmaceutical industry and specifically to the development of a medicament for the treatment of cerebrovascular, neurodegenerative and psychiatric diseases. Its active ingredient is recombinant human erytoprotein (rHuEPO) with low sialic acid content. During rHuEPO production, this glycoprotein is obtained with different sialic acid contents; if less than 40% of the molecule is protected with (basic) sialic acid, it is not biologically active in the systemic mode as it is then rendered inactive by liver enzymes. Surprisingly, we found that intranasal administration of basic rHuEPO intensified therapeutic activity compared to acid rHuEPO. The basic rHuEPO nasal formulations presented herein incorporate bioadhesive polymers that increase the residence time in the nasal cavity, thereby increasing their therapeutic effectiveness. They also include other auxiliary substances such as preservatives, surfactants, pH regulators, isotonic agents and protein stabilizers.