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OwnerAndrew S. Janoff, Thomas D. Madden +7inventors
InventorsAndrew S. Janoff, Thomas D. Madden, Pieter R. Cullis, John J. Kearns, Anthony G. Durning, Lawrence Boni, Robert P. Lenk, Robert Klimchak, Joel Portnoff
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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.
A composition comprising a bioactive agent—lipid complex (“HDLC”) wherein the ratio of bioactive agent to lipid is at least about 6 mole percent.
A method for forming an HDLC or a liposome comprising a drug and a lipid, wherein the method comprises the steps of:
A method for preparing a composition comprising an HDLC, wherein the method comprises the steps of:
A method for preparing a composition comprising an HDLC, wherein the method comprises the steps of:
A method for preparing an HDLC, wherein the method comprises the steps of:
A method for preparing an HDLC, wherein the method comprises the steps of:
A method for forming an HDLC comprising the steps of forming a preparation by the MLV process which contains amphotericin B and DMPC:DMPG in a 7:3 mole ratio, and heating the preparation.
A method for determining the toxicity of an HDLC by reading the absorbance spectrum of the HDLC preparation and measuring the peak intensity.
A method for preparing a composition comprising an HDLC liposome comprising a drug and a lipid in a high drug:mol ratio, wherein the method comprises the steps of:
A composition comprising a lipid and a bioactive agent, wherein the mole percent of the bioactive agent is from about 6 to about 50 mole percent.
Dependencies are inferred from the claim text.