Compositions and methods for modulating physiology of...

A - Human Necessities – 61 – K

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A61K 38/00 (2006.01) A61K 9/00 (2006.01) A61K 38/17 (2006.01) A61K 38/18 (2006.01) A61K 38/21 (2006.01) A61K 38/27 (2006.01) A61K 38/28 (2006.01) A61K 45/06 (2006.01) A61K 47/42 (2006.01) C07K 14/705 (2006.01)

Patent

CA 2487712

Compositions and methods are provided that include a biologically active agent and a permeabilizing agent effective to enhance mucosal delivery of the biologically active agent in a mammalian subject. The permeabilizing agent reversibly enhances mucosal epithelial paracellular transport, typically by modulating epithelial junctional structure and/or physiology at a mucosal epithelial surface in the subject. This effect typically involves inhibition by the permeabilizing agent of homotypic or heterotypic binding between epithelial membrane adhesive proteins of neighboring epithelial cells. Target proteins for this blockade of homotypic or heterotypic binding can be selected from various related junctional adhesion molecules (JAMs), occludins, or claudins. The permeabilizing agent is typically a peptide or peptide analog or mimetic, often selected or derived from an extracellular domain of a mammalian JAM, occludin or claudin protein.

L'invention concerne des compositions et des méthodes faisant intervenir un agent biologiquement actif et un agent perméabilisant améliorant l'administration par voie muqueuse dudit agent biologiquement actif chez un mammifère. L'agent perméabilisant accroît de manière réversible le transport paracellulaire épithélial par voie muqueuse, généralement par modulation de la physiologie et/ou de la structure jonctionnelle épithéliale au niveau d'une surface épithéliale de muqueuse chez le mammifère. Cet effet implique généralement l'inhibition par l'agent perméabilisant d'une liaison homotypique ou hétérotypique entre des protéines adhésives de membrane épithéliale de cellules épithéliales voisines. Des protéines cibles pour ce blocage de liaison homotypique ou hétérotypique peuvent être choisies parmi diverses molécules d'adhésion jonctionnelle (JAM) apparentées, des occludines ou des claudines. Ledit agent perméabilisant est généralement un peptide ou un analogue ou mimétique peptidique, souvent choisi ou dérivé à partir d'un domaine extracellulaire d'une protéine de mammifère de type JAM, occludine ou claudine.

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