Methods of making liposomes containing...

A - Human Necessities – 61 – K

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A61K 41/00 (2006.01) A61K 9/127 (2006.01) A61K 31/40 (2006.01) A61K 31/409 (2006.01) A61K 47/24 (2006.01) A61K 47/26 (2006.01)

Patent

CA 2227761

Methods for making a pharmaceutical composition containing liposomes, which liposomes comprise a therapeutically acceptable amount of a hydro-monobenzoporphyrin photosensitizer and a mixture of phospholipids comprising egg phosphatidyl glycerol ("EPG") and dimyristoyl phosphatidyl choline ("DMPC"). The method comprises the steps of: a) combining the photosensitizer and the phospholipids in a molar ratio of about 1:7.0 or more phospholipid in the presence of an organic solvent; b) removing the organic solvent to form a lipid film; c) hydrating the lipid film with an aqueous solution at a temperature below about 300 °C, to form coarse liposomes containing a photosensitizer-phospholipid complex; and d) homogenizing or reducing the particle size of the coarse liposomes to a particle size range of about 150 to 300 nm at a temperature below about 300 °C. The invention also contemplates the liposomal pharmaceutical compositions themselves.

La présente invention se rapporte à des procédés de fabrication d'une composition pharmaceutique contenant des liposomes qui représentent une quantité thérapeutiquement acceptable d'un photosensibilisateur d'hydro-monobenzoporphyrine et d'un mélange de phospholipides comprenant du glycérol phosphatidyle d'oeuf (EPG) et de la dimyristoyle phosphatidyle choline (DPMC). Le procédé consiste à (a) combiner le photosensibilisateur et les phospholipides dans un rapport molaire d'environ 1:7,0 ou avec plus de phospholipides en présence d'un solvant organique; (b) éliminer le solvant organique pour former un film lipidique; (c) hydrater le film lipidique avec une solution aqueuse à une température inférieure à environ 300 DEG C pour former des liposomes grossiers contenant un complexe photosensibilisateur-phospholipide; et (d) homogénéiser ou diminuer la taille des particules des liposomes grossiers pour obtenir une taille de particule comprise entre 150 et 300nm à une température inférieure à environ 300 DEG C. L'invention se rapporte également aux compositions pharmaceutiques liposomiques elles-mêmes.

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