Inflammation-regulating compositions and methods

A - Human Necessities – 61 – K

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Details

A61K 47/48 (2006.01) A61P 1/00 (2006.01) A61P 17/02 (2006.01) A61P 19/02 (2006.01) A61P 29/00 (2006.01)

Patent

CA 2734577

The various embodiments provide a composition that provides local control over inflammation. The composition localizes the activities of the cytokine-neutralizing antibodies to the site of inflammation through covalent attachment to hydrophilic matrices. The various embodiments including a hydrophilic polymer, a ligand binding moiety covalently attached to the polymer, and optionally, a cellular adhesion peptide covalently attached to the polymer. The hydrophilic polymer may be a glycosaminoglycan such as hyaluronan. The cellular adhesion peptide may be a linear RGD peptide sequence covalently attached to the polymer. The ligand binding moiety may be a monoclonal antibody covalently attached to the polymer. The antibody may be selected from the group consisting of an anti-IL-1.BETA., an anti-IL-6, an anti-TNF-.alpha., and combinations thereof. The polymer functions as a substrate or matrix for cell migration and tissue regeneration. The RGD peptide functions to promote cellular proliferation, migration and attachment to the polymer. The monoclonal antibody functions to

L'invention concerne une composition qui offre un contrôle local de l'inflammation. La composition localise les activités des anticorps de neutralisation de cytokine sur le site d'inflammation par attache covalente à des matrices hydrophiles. Les divers modes de réalisation comprennent un polymère hydrophile, une fraction de liaison de ligand attachée par covalence au polymère, et facultativement, un peptide d'adhérence cellulaire attaché par covalence au polymère. Le polymère hydrophile peut être un glyosaminoglycan tel que l'hyaluronan. Le peptide d'adhérence cellulaire peut être une séquence de peptides RGD linéaire attachée par covalence au polymère. La fraction de liaison de ligand peut être un anticorps monoclonal attaché par covalence au polymère. L'anticorps peut être choisi parmi le groupe constitué par un anti-IL-1, un anti-IL-6, un anti-TNF- et des combinaisons de ceux-ci. Le polymère fonctionne comme un substrat ou une matrice pour la migration de cellules et la régénération tissulaire. Le peptide RGD sert à favoriser la prolifération cellulaire, la migration et l'attache au polymère. L'anticorps monoclonal sert à inhiber la réponse inflammatoire.

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