US5077057A
Expired / Lapsed
US
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Preparation of liposome and lipid complex compositions
Assignee: University of California, San Diego
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Filing: 1990-10-29
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Granted: 1991-12-31
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Expires: 2010-10-29
Abstract
Abstract Liposome and lipidic particle formulations of compounds are prepared by dissolving in a solution of liposome-forming lipids in an aprotic solvent such as DMSO, optionally containing a lipid-solubilizing amount of a lower alkanol, and injecting the resulting solution into an aqueous solution. The resulting liposome or lipidic particle suspension may then be dialyzed or otherwise concentrated. This method is particularly useful for compounds which are poorly-soluble in aqueous solution, but is generally useful for any compound or combination of compounds which can be dissolved in the aprotic solvent or aprotic solvent/lower alkanol mixture.
Inventors
- 👤 Francis C. Szoka, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 04:20
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1617; A61K9/10; A61K9/127; A61K9/1277; Y; Y10; Y10S; Y10S436/00; Y10S436/829
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
71 words
A process for preparing a lipid suspension of defined particle size encapsulating a useful compound, which process comprises: dissolving said useful compound and an encapsulating amount of a suitable lipid in a sufficient amount of a solvent mixture comprising a non-halogenated hydrocarbon aprotic solvent to provide a compound/lipid solution; and extruding said compound/lipid solution through a suitably-sized aperture into an aqueous solution to form a lipid-compound suspension of defined particle size.
Claim 2
Dependent Claim
71 words
A process for preparing a lipid suspension of defined particle size encapsulating a useful compound, which process comprises: dissolving said useful compound and an encapsulating amount of a suitable lipid in a sufficient amount of a solvent mixture comprising a non-halogenated hydrocarbon aprotic solvent to provide a compound/lipid solution; and extruding said compound/lipid solution through a suitably-sized aperture into an aqueous solution to form a lipid-compound suspension of defined particle size.
Claim 3
Dependent Claim
19 words
The process of claim 1 wherein said useful compound exhibits poor solubility in water, alcohols, and halogenated hydrocarbon solvents.
Claim 4
Dependent Claim
18 words
The process of claim 2 wherein said lipid suspension of defined particle size comprises a suspension of liposomes.
Claim 5
Dependent Claim
27 words
The process of claim 3 wherein said aprotic solvent is selected from the group consisting of dimethylsulfoxide, dioxane, dimethylformamide, acetonitrile, dimethylacetamide, sulfolane, gamma butyrolactone, 1-methyl-2-pyrrolidinone, and methylpyrroline.
Claim 6
Dependent Claim
22 words
The process of claim 3 wherein said useful compound is selected from the group consisting of cisplatin, doxorubicin, epinephrine, mebendazole, and niridazole.
Claim 7
Dependent Claim
18 words
The process of claim 1 wherein said solvent mixture further comprises a lipid-solubilizing amount of a lower alkanol.
Claim 8
Dependent Claim
11 words
The process of claim 6 wherein said lower alkanol is ethanol.
Claim 9
Dependent Claim
19 words
The process of claim 2 wherein said lipid suspension of defined particle size comprises a suspension of lipidic particles.
Claim 10
Dependent Claim
21 words
The process of claim 8 wherein said useful compound is selected from the group consisting of amphotericin B, nystatin, and primaricin.
Claim 11
Dependent Claim
22 words
The process of claim 9, wherein said lipid and said poorly-soluble compound are present in a ratio of about 1:1 to 1:5.
Claim 12
Dependent Claim
50 words
The process of claim 1 wherein said suitable lipid is selected from the group consisting of egg phosphatidylcholine, egg phosphatidylglycerol, dipalmitoylphosphatidylcholine, cholesterol, cholesterol sulfate and salts thereof, cholesterol hemisuccinate and salts thereof, cholesterol phthalate and salts thereof, cholesterol phosphate and salts thereof, cholesterylphosphorylcholine, 3,6,9-trioxaoctan-1-ol-cholesteryl-3e-ol, dimyristoylphosphatidylglycerol, dimyristoylphosphatidylcholine, and hydrogenated soy phosphatidylcholine.
Claim 13
Dependent Claim
16 words
The process of claim 1 which further comprises concentrating said lipid suspension of defined particle size.
Claim 14
Dependent Claim
72 words
A process for preparing a lipid suspension of defined particle size encapsulating a useful aqueoussoluble compound, which process comprises: dissolving an encapsulating amount of a suitable lipid in a sufficient amount of a solvent mixture comprising a non-halogenated hydrocarbon aprotic solvent to provide a lipid solution; and extruding said lipid solution through a suitably-sized aperture into an aqueous solution of said useful compound to form a lipid-compound suspension of defined particle size.
Claim 15
Dependent Claim
72 words
A process for preparing a lipid suspension of defined particle size encapsulating a useful aqueoussoluble compound, which process comprises: dissolving an encapsulating amount of a suitable lipid in a sufficient amount of a solvent mixture comprising a non-halogenated hydrocarbon aprotic solvent to provide a lipid solution; and extruding said lipid solution through a suitably-sized aperture into an aqueous solution of said useful compound to form a lipid-compound suspension of defined particle size.
Claim 16
Dependent Claim
96 words
The process of claim 13 wherein said useful compound is selected from the group consisting of weak acids, weak bases, chelating agents, amino acids, fluorescent molecules, radiocontrast agents, radioactive isotopes and compounds, paramagnetic compounds, spin labels, soluble antibiotics,-antiviral compounds, nucleotides and their phosphorylated derivatives, carbohydrates, peptides, oxytocin, lutenizing hormone releasing hormone, muramylpeptide derivatives and analogs, calcitonin, insulin, protease inhibitors, reinin inhibitors, oligonucleotides and their derivatives, ribonucleic acids, deoxyribonucleic acids, modified nucleic acids, superoxide dismutase, human growth hormone, interferons, colony stimulating factors, nerve growth factor, transforming growth factor alpha and beta, epidermal growth factor, IL-1, and IL-2.
Claim 17
Dependent Claim
18 words
The process of claim 13 wherein said lipid suspension of defined particle size comprises a suspension of liposomes.
Claim 18
Dependent Claim
27 words
The process of claim 15 wherein said aprotic solvent is selected from the group consisting of dimethylsulfoxide, dioxane, dimethylformamide, acetonitrile, dimethylacetamide, sulfolane, gamma butyrolactone, 1-methyl-2-pyrrolidinone, and methylpyrroline.
Claim 19
Dependent Claim
18 words
The process of claim 15 wherein said solvent mixture further comprises a lipid-solubilizing amount of a lower alkanol.
Claim 20
Dependent Claim
13 words
The process of claim 17 wherein said lower alkanol is ethanol or methanol.
Claim 21
Dependent Claim
49 words
The process of claim 13 wherein said lipid is selected from the group consisting of egg phosphatidylcholine, egg phosphatidylglycerol, dipalmitroylphosphatidylcholine, cholesterol, cholesterol sulfate and salts thereof, cholesterol hemisuccinate and salts thereof, cholesterol phthalate and salts thereof, cholesterol phosphate and salts thereof, cholesterylphosphorylcholine, 3,6,9-trioxaoctan-1-ol-cholesteryl-3-e-ol, dimyristoylphosphatidylglycerol, dimyristoylphosphatidylcholine, and hydrogenated soy phosphatidylcholine.
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