C - Chemistry – Metallurgy – 08 – G
Patent
C - Chemistry, Metallurgy
08
G
C08G 65/329 (2006.01) A61K 9/127 (2006.01)
Patent
CA 2379060
Liposomes containing PEG-substituted neutral lipopolymers provide similar circulation times to liposomes incorporating conventional, negatively charged PEG-substituted phospholipids. Use of the uncharged lipopolymers can also present advantages in terms of interactions with cell surfaces and reduced leakage of charged substances, particularly cationic drugs, from the liposomes. The lipopolymers are of formula (I) wherein each of R1 and R2 is an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms, n is about 10 to about 300, Z is selected from the group consisting of hydroxy, alkoxy, benzyloxy, carboxylic ester, sulfonic ester, alkyl or aryl carbonate, amino, and alkylamino, and the linkage L is selected from the group consisting of (i) -X-(C=O)-Y-CH2-, (ii) -X-(C=O)-, and (iii) -X-CH2-, wherein X and Y are independently selected from oxygen, NH, and a direct linkage.
L'invention concerne des lipopolymères neutres substitués du PEG contenant des liposome présentant des temps de circulation identiques vers les liposomes incorporant des phospholipides substitués du PEG négativement chargés classiques. L'utilisation des lipopolymères non chargés peut également présenter des avantages en termes d'interactions avec les surfaces cellulaires et de fuites réduites de substances chargées, en particulier des médicaments cationiques, à partir des liposomes. La formule (I) des lipopolymères, dans laquelle R?1¿ et R?2¿ représentent chacun une chaîne alkyle ou alcényle ayant 8 à 24 atomes de carbone environ; n se situe entre environ 10 et 300; Z est choisi dans le groupe hydroxy, alcoxy, benzyloxy, ester carboxylique, ester sulfonique, carbonate d'alkyle ou d'aryle, amino et alkylamino, et la liaison L est choisie dans le groupe (i) -X-(C=O)-Y-CH¿2?, (ii) -X-(C=O)-, et (iii) X-CH¿2?-, X et Y étant indépendamment choisis parmi l'oxygène, NH, et une liaison directe.
Zalipsky Samuel
Alza Corporation
Smart & Biggar
LandOfFree
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