Process for the preparation of liposomes
First Claim
1. A process for the preparation of synthetic liposomes, including the steps of dispersing a first aqueous liquid with the aid of ultrasonic vibration in a carrier liquid which is insoluble in water or only slightly soluble in water and has a density less than that of water, in the presence of at least one compound of the general formula XY, where X represents a hydrophilic polar group and Y represents a hydrophobic non-polar group, selected from the group consisting of phospholipids and lipid-like substances in which the hydrophilic polar group X is selected from phosphato, carboxylic, sulphato, amino, hydroxyl and choline;
- and in which the non-polar hydrophobic group Y is selected from saturated or unsaturated hydrophobic aliphatic hydrocarbon groups and such aliphatic hydrocarbon groups which are substituted by at least one aromatic or cycloaliphatic group and mixtures of such phospholipids and lipid-like substances, so as to form a colloidal dispersion of the first aqueous liquid in the carrier liquid, the dispersed phase globules, each being bounded by a monomolecular film of the compound of the general formula XY;
combining this dispersion with a second aqueous liquid to form a heterogeneous two-layer system comprising an upper liquid layer formed by the dispersion and a lower liquid layer formed by the second aqueous liquid, the two layers being separated by the monomolecular film of the compound of formula XY; and
then centrifuging the two-layer system at an angular velocity sufficient for the dispersed globules of the first aqueous liquid to be forced by gravity through the monomolecular separating film of the compound XY and into the lower layer of the second aqueous liquid.
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Abstract
Synthetic liposomes, for example containing a biologically active substance, are prepared by dispersing a first aqueous liquid with the aid of ultrasonic vibration in a water-immiscible carrier liquid less dense than water in the presence of a compound of the formula XY where X is a hydrophilic polar group and Y is a hydrophobic non-polar group to form dispersed globules of the first aqueous liquid each bounded by a monomolecular layer of the compound XY; adding this dispersion to a second aqueous liquid to form a two layer system separated and bounded by a monomolecular second layer of the compound XY and then centrifuging the system to force the dispersed globules through the second boundary layer of the compound XY and into the second aqueous liquid.
211 Citations
13 Claims
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1. A process for the preparation of synthetic liposomes, including the steps of dispersing a first aqueous liquid with the aid of ultrasonic vibration in a carrier liquid which is insoluble in water or only slightly soluble in water and has a density less than that of water, in the presence of at least one compound of the general formula XY, where X represents a hydrophilic polar group and Y represents a hydrophobic non-polar group, selected from the group consisting of phospholipids and lipid-like substances in which the hydrophilic polar group X is selected from phosphato, carboxylic, sulphato, amino, hydroxyl and choline;
- and in which the non-polar hydrophobic group Y is selected from saturated or unsaturated hydrophobic aliphatic hydrocarbon groups and such aliphatic hydrocarbon groups which are substituted by at least one aromatic or cycloaliphatic group and mixtures of such phospholipids and lipid-like substances, so as to form a colloidal dispersion of the first aqueous liquid in the carrier liquid, the dispersed phase globules, each being bounded by a monomolecular film of the compound of the general formula XY;
combining this dispersion with a second aqueous liquid to form a heterogeneous two-layer system comprising an upper liquid layer formed by the dispersion and a lower liquid layer formed by the second aqueous liquid, the two layers being separated by the monomolecular film of the compound of formula XY; and
then centrifuging the two-layer system at an angular velocity sufficient for the dispersed globules of the first aqueous liquid to be forced by gravity through the monomolecular separating film of the compound XY and into the lower layer of the second aqueous liquid. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
- and in which the non-polar hydrophobic group Y is selected from saturated or unsaturated hydrophobic aliphatic hydrocarbon groups and such aliphatic hydrocarbon groups which are substituted by at least one aromatic or cycloaliphatic group and mixtures of such phospholipids and lipid-like substances, so as to form a colloidal dispersion of the first aqueous liquid in the carrier liquid, the dispersed phase globules, each being bounded by a monomolecular film of the compound of the general formula XY;
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13. A process for the preparation of synthetic liposomes, comprising the steps of (a) dispersing a first aqueous liquid consisting of a solution of a biologically active substance, with the aid of ultrasonic vibration in a carrier liquid which is insoluble in water or only slightly soluble in water and has a density less than that of water, in the presence of at least one interface compound selected from the group consisting of lecithin, phosphatidylethanolamine, lysolecithin, lysophosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cardiolipin, phosphatidic acid and the cerebrosides or a mixture thereof with at least one lipid selected from the group consisting of stearylamine, dicetyl phosphate, cholesterol and tocopherol, so as to form a colloidal dispersion of the first aqueous liquid in the carrier liquid, the dispersed phase globules each being bounded by a monomolecular film of the said interface compound;
- (b) combining this dispersion with a second aqueous liquid to form a heterogeneous two-layer system comprising an upper liquid layer formed by the dispersion and a lower liquid layer formed by the second aqueous liquid, the two layers being separated by the monomolecular film of the said interface compound; and
(c) centrifuging the two layer system at an angular velocity of about 30,000 rev/min to force the dispersed globules of the first aqueous liquid by gravity through the monomolecular separating film of the interface compound and into the lower layer of the second aqueous liquid.
- (b) combining this dispersion with a second aqueous liquid to form a heterogeneous two-layer system comprising an upper liquid layer formed by the dispersion and a lower liquid layer formed by the second aqueous liquid, the two layers being separated by the monomolecular film of the said interface compound; and
Specification