Liposome having inner water phase containing sulfobutyl ether cyclodextrin salt
A liposome comprising bilayer and inner water phase is disclosed. Said inner water phase contains sulfobutyl ether cyclodextrin and active compound. Said sulfobutyl ether cyclodextrin is sulfobutyl ether α-cyclodextrin, sulfobutyl ether β-cyclodextrin, or sulfobutyl ether γ-cyclodextrin.
1. A liposome comprising bilayer and inner water phase, wherein the inner water phase comprises a salt of sulfobutyl ether cyclodextrin and an active compound, wherein the salt of sulfobutyl ether cyclodextrin is formed by sulfobutyl ether cyclodextrin with one or more of ammonium hydroxide, triethylamine and triethanolamine, and
wherein the active compound is one or more of vinorelbine, vincristine, topotecan and irinotecan.
2. The liposome according to claim 1 , wherein the sulfobutyl ether cyclodextrin is sulfobutyl ether-α-cyclodextrin, sulfobutyl ether-β-cyclodextrin or sulfobutyl ether-γ-cyclodextrin.
3. The liposome according to claim 1 , wherein the sulfobutyl ether cyclodextrin has about 6.5 sulfo groups at average per molecule.
4. The liposome according to claim 1 , wherein the bilayer comprises phospholipid, cholesterol and hydrophilic polymer-modified lipid.
5. A process for preparing the liposome according to claim 1 , comprising:
(1) hydrating lipid phase powders with aqueous solution of sulfobutyl ether cyclodextrin or its salt, to form a blank liposome comprising the aqueous solution of sulfobutyl ether cyclodextrin or its salt as inner water phase,
(2) removing the salt of sulfobutyl ether cyclodextrin in the outer phase of the blank liposome obtained in step (1), to form an anion gradient,
(3) optionally, if the salt of sulfobutyl ether cyclodextrin is a metal ion salt, adding an ionophore of the metal ion to the outer phase of the blank liposome obtained in step (2) to form a pH gradient, and
(4) incubating the blank liposome obtained in step (2) or (3) with the active compound in aqueous solution, to encapsulate the active compound into the liposome.
6. A liposomal pharmaceutical preparation, comprising the liposome according to claim 1 and a pharmaceutically acceptable carrier and/or excipient.
7. A liposomal pharmaceutical preparation according to claim 6 , wherein the carrier and/or excipient comprises osmotic regulator and/or antioxidant.
8. A method of treating a tumor in a patient, comprising administering the liposome according to claim 1 to the patient in need thereof, wherein the active compound in the liposome is one or more of vinorelbine, vincristine, topotecan and irinotecan.