Conjugate having a cleavable linkage for use in a liposome

Details Conjugate having a cleavable linkage for use in a liposome Conjugate having a cleavable linkage for use in a liposome

A - Human Necessities

61

K

A61K 47/48 (2006.01) C07C 323/12 (2006.01) C07D 203/00 (2006.01) C07D 209/00 (2006.01) C07D 239/54 (2006.01) C07D 487/14 (2006.01)

Patent

CA 2369595

Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

Divulgation de conjugués d'une entité hydrophobe, comme un lipide, liés à un agent thérapeutique par une liaison dithiobenzyle pouvant être brisée. La liaison dithiobenzyle peut être brisée au moyen d'une thiolyse douce, conduisant à la libération de l'agent thérapeutique sous sa forme d'origine. Ladite liaison est stable dans des conditions non réductrices. Ledit conjugué peut être incorporé dans des liposomes pour une administration in vivo et la libération de l'agent thérapeutique en réponse à des conditions réductrices in vivo endogènes ou en réponse à l'administration d'un agent réducteur exogène.

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