Methods for the treatment and prevention of diseases of...

A - Human Necessities – 61 – K

Patent

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A61K 38/48 (2006.01) A61K 38/17 (2006.01) A61K 39/395 (2006.01)

Patent

CA 2517006

Methods are described for dilating biological conduits by removing elastin and remodeling collagens in the wall of the conduit. Methods include the use of agents that increase the release of endogenous elastase and collagenase in the wall of the conduit, either by cells that are normally present in the wall of the conduit or by inflammatory cells that are attracted to the conduit, thereby providing additional conduit dilation. Methods also include the use of agents that increase conduit wall permeability and expose elastin and collagen fibers. Methods also include removing components of the extracellular matrix of arteries and veins leading to an inhibition of intimal hyperplasia in the wall of the vessels by decreasing biomechanical stimuli directed toward the cells in the wall of the vessel. Methods further include the use of agent that degrade microfibers, in addition to elastin, in order to decrease the resynthesis of elastin. Methods also include the use of agent that stabilize the diameter of aneurysmal arteries by blocking cell surface receptors in the wall of the aneurysmal artery that are important in the recruitment of inflammatory cells.

La présente invention concerne des techniques permettant de dilater des conduits biologiques en retirant l'élastine et en remodelant des collagènes dans la paroi du conduit. Ces techniques utilisent des agents qui augmentent la libération d'élastase et de collagenase endogènes dans la paroi du conduit, soit par des cellules qui sont normalement présentes dan la paroi de ce conduit, soit par des cellules inflammatoires qui sont attirées vers ce conduit, de qui permet d'obtenir une dilatation du conduit additionnelle. Des techniques utilisent aussi des agents qui augmentent la perméabilité de la paroi du conduit et exposent de l'élastine et des fibres de collagène. Des techniques consistent aussi à retirer des éléments de la matrice extracellulaire d'artères ou de veines, entraînant l'inhibition de l'hyperplasie dans la paroi de ces vaisseaux en diminuant les stimuli biochimiques dirigés vers les cellules de cette paroi. Des techniques utilisent aussi des agents qui dégradent des microfibres, en plus de l'élastine, de façon à diminuer la resynthèse de l'élastine. Des techniques utilisent aussi un agent qui stabilise le diamètre d'artères anévrysmales qui jouent un rôle important dans le recrutement des cellules inflammatoires.

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