| CPC A61K 9/1277 (2013.01) [B01D 17/0217 (2013.01); B04B 11/02 (2013.01); B04B 11/04 (2013.01); C09B 67/0097 (2013.01)] | 22 Claims |
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1. A method of encapsulating active ingredients in liposomes, comprising:
a solution of the active ingredient and
at least one bilayer composed of two at least monomolecular layers of at least one first amphiphilic compound and at least one second amphiphilic compound,
wherein the active ingredient solution is encapsulated by the at least one bilayer, comprising the following steps:
(a) providing the active ingredient solution of the active ingredient to be encapsulated by dissolving the active ingredient in at least one solvent;
(b) providing a first emulsion by emulsifying the active ingredient solution from step (a) in at least one first liquid having zero or sparing miscibility with the at least one solvent of the active ingredient solution, in the presence of the at least one first amphiphilic compound, in order to accumulate an at least monomolecular inner layer of the at least one first amphiphilic compound on droplets of the active ingredient solution emulsified in the at least one first liquid;
(c) providing a mixture of a liquid phase having zero or sparing miscibility with the at least one first liquid of the first emulsion from step (b) with the at least one second amphiphilic compound;
(d) contacting the first emulsion composed of the at least one first liquid and having the droplets of the active ingredient solution that are emulsified therein and having the at least monomolecular inner layer of the at least one first amphiphilic compound that has been accumulated thereon from step (b) with the mixture of the liquid phase with the at least one second amphiphilic compound from step (c) to form a phase boundary between the first emulsion from step (b) and the mixture from step (c), wherein the at least one second amphiphilic compound is enriched at the phase boundary; and
(e) centrifuging the first emulsion from step (b) and the mixture from step (c) that are in contact with one another via the phase boundary, in order to transfer the droplets of the active ingredient solution present in the first emulsion and having the at least monomolecular inner layer of the at least one first amphiphilic compound that has been accumulated thereon from the at least one first liquid of the first emulsion from step (b) into the liquid phase of the mixture from step (c), wherein, when the droplets of the active ingredient solution having the at least monomolecular inner layer of the at least one first amphiphilic compound that has been accumulated thereon passes the phase boundary, the at least one second amphiphilic compound enriched there is accumulated on the at least monomolecular inner layer of the at least one first amphiphilic compound of the droplets of the active ingredient solution to form an at least monomolecular outer layer thereof, in order to produce the at least one bilayer composed of the two at least monomolecular layers of the at least one first amphiphilic compound and the at least one second amphiphilic compound;
wherein;
the mixture of the liquid phase with the at least one second amphiphilic compound used in step (c) is a second emulsion of the liquid phase and at least one second liquid having zero or sparing miscibility therewith with the at least one second amphiphilic compound, wherein the at least one second liquid is emulsified in the liquid phase in the presence of the at least one second amphiphilic compound in order to accumulate an at least monomolecular layer of the at least one second amphiphilic compound on the droplets of the at least one second liquid emulsified in the liquid phase and to immobilize the at least one second amphiphilic compound on these droplets in this way; and
on centrifugation of the first emulsion from step (b) and the mixture in the form of the second emulsion from step (c) that are in contact with one another via the phase boundary, the droplets of the at least one second liquid with the at least monomolecular layer of the at least one second amphiphilic compound accumulated thereon are constantly transferred from the liquid phase of the second emulsion to the phase boundary between the first emulsion and the second emulsion, in order to constantly enrich the at least one second amphiphilic compound at the phase boundary.
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