US 6,406,713 B1Granted

Methods of preparing low-toxicity drug-lipid complexes

AssigneeThe Liposome Company, Inc.

InventorsAndrew S. Janoff, Thomas D. Madden, Pieter R. Cullis, John J. Kearns, Anthony G. Durning

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Abstract

Methods and compositions are described for nonliposomal lipid complexes in association with toxic hydrophobic drugs such as the polyene antibiotic amphotericin B. Lipid compositions are preferably a combination of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in about a 7:3 mole ratio. The lipid complexes contain a bioactive agent, and may be made by a number of procedures, at high drug:lipid ratios. These compositions of high drug:lipid complexes (HDLCs) may be administered to mammals such as humans for the treatment of infections, with substantially equivalent or greater efficacy and reduced drug toxicities as compared to the drugs in their free form. Also disclosed is a novel liposome-loading procedure, which may also be used in the formation of the HDLCs.

Claims11

Dependent claims

A method of preparing a drug-lipid complex comprising the steps of:

(a) dissolving a lipid which comprises a fatty acid or a phospholipid in an organic solvent selected from the group consisting of chloroform, methanol, dimethylsulfoxide (DMSO), methylene chloride, chloroform:methanol mixtures and benzene:methanol mixtures;
(b) dissolving a polyene antifungal agent in an organic solvent;
(c) combining the product of step (a) and the product of step (b) so as to obtain a mixture of the lipid solution and the agent solution;
(d) adding an aqueous phase to the product of step (c);
and,
(e) removing organic solvent from the mixture of step (c),
wherein the complex has no captured volume, wherein the complex is substantially free of liposomes and wherein the relative amount of polyene antifungal agent used is such that the agent comprises from about 25 to 50 mole percent of the complex.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/430,661Filed 28 Apr 1995 · division
Priority: 5 Mar 1987
Granted: 18 Jun 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

A61K 9/127
Dispersions; Emulsions: synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 9/1277
Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant: preparation processes;…
A61K 9/1617
Excipients; Inactive ingredients: organic compounds, e.g. phospholipids, fats
A61K 31/7048
Compounds having saccharide radicals and heterocyclic rings: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin,…

Family

Application07/022,157Parent of this continuation-in-part · filed 5 Mar 1987
Application07/069,908Parent of this continuation-in-part · filed 6 Jul 1987
Application07/136,267Parent of this continuation-in-part · filed 22 Dec 1987
Application07/164,580Parent of this continuation-in-part · filed 7 Mar 1988
Application07/236,700Parent of this continuation · filed 25 Aug 1988
Application07/876,121Parent of this division · filed 29 Apr 1992
Application07/876,121Parent of this continuation
Application07/236,700Parent of this continuation-in-part
US 4,963,297 AParent of this continuation-in-part
US 6,406,713 B1This patent

From the US filing history. Foreign family members aren’t listed.