Lipid-based drug delivery systems containing phospholipase...

C - Chemistry – Metallurgy – 07 – F

Patent

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Details

C07F 9/10 (2006.01) A61K 9/107 (2006.01) A61K 9/127 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2399821

The present invention relates to a lipid-based drug delivery system for administration of a lysolipid derivative present in prodrug form, said prodrug furthermore being a substrate for extracellular phospholipase A2 to the extent that an organic radical can be hydrolytically cleaved off, whereas the aliphatic group of the lysolipid derivative remains substantially unaffected, said system having included therein lipopolymers or glycolipids so as to present hydrophilic chains on the surface of the system. Particularly interesting lipid derivatives are ether lipids and ether lipids in which drug substance is covalently attached in the sn-2-position. Pharmaceutical compositions comprising the drug delivery system can be used in the targeted treatment of various disorders, e.g. cancer, infectious, and inflammatory conditions, etc., i.e. disorders and diseases associated with or resulting from increased levels of extracellular PLA2 activity in the diseased tissue.

Cette invention concerne un système d'administration de médicaments à base de lipides, plus précisément d'un dérivé lysolipidique présent dans le promédicament. Ce promédicament constitue par ailleurs un substrat pour la phospholipase A2 extracellulaire dans la mesure où un radical organique peut être clivé hydrolitiquement, le groupe aliphatique du dérivé lysolipidique étant sensiblement inaffecté. Ledit système renferme des polymères ou des glycolipides et présente ainsi des chaînes hydrophiles à sa surface. D'un intérêt tout particulier parmi les dérivés lipidiques sont des éther lipides et des éthers lipides dans lesquels une substance médicamenteuse est reliée par covalence dans la position sn-2. Les compositions pharmaceutiques comprenant ledit système d'administration de médicament peuvent s'utiliser pour le traitement ciblé de diverses pathologies, dont le cancer, des maladies infectieuses et inflammatoires, etc., en d'autres termes pour le traitement de troubles et de maladies en rapport avec des niveaux accrus d'activité extracellulaire PLA¿2? Dans le tissu malade, ou bien découlant de ces niveaux accrus.

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