Compositions and methods for enhancing drug delivery across...

A - Human Necessities – 61 – K

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A61K 9/02 (2006.01) A61K 31/155 (2006.01) A61K 38/03 (2006.01) A61K 38/16 (2006.01) A61K 47/48 (2006.01) C07C 257/00 (2006.01) C07C 279/00 (2006.01) C07K 4/00 (2006.01) C07K 14/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2438326

This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length (see Figure 44).

L'invention porte sur des compositions et des méthodes renforçant la diffusion de médicaments et d'autres agents à travers des tissus épithéliaux, tels que la peau, le tractus gastro-intestinal, l'épithélium pulmonaire, et analogues. Ces compositions et méthodes servent également à la diffusion de médicaments à travers des tissus endothéliaux, tels que la barrière hématoencéphalique. Ces compositions et méthodes recourent à un transporteur renforçant la diffusion, lequel présente suffisamment de fragments de chaînes latérales guanidino ou amidino pour renforcer la diffusion d'un composé conjugué au réactif à travers une ou plusieurs couches de tissu, par rapport à celle d'un composé non conjugué. Les polymères renforçant la diffusion comportent, par exemple, des molécules de polyarginine dont la longueur est de préférence comprise entre environ 6 et 25 résidus.

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