US4744989A
Expired / Lapsed
US
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Method of preparing liposomes and products produced thereby
Assignee: ER Squibb and Sons LLC
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Filing: 1986-03-21
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Granted: 1988-05-17
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Expires: 2006-03-21
Abstract
Abstract A method is provided for preparing stable liposome precursors in the form of a water-soluble carrier material coated with a predetermined amount of a thin film of liposome components, which method includes the steps of dissolving at least one liposome-forming amphipathic lipid, optionally, at least one biologically active compound, and, optionally, at least one adjuvant in a suitable organic solvent and employing the resulting organic solution to coat a suitable water-soluble carrier material to form thin film of predetermined amount of liposome components thereon. Upon exposing the coated carrier material to water, the thin films of liposome components hydrate and the carrier material dissolves to give liposome preparations.
Inventors
- 👤 Nicholas I. Payne
- 👤 Peter Timmins
- 👤 Cheryl V. Ambrose
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:00
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
220 words
A method for preparing a stable liposome precursor in the form of a thin film of liposomal components of predetermined amount coated on a water-soluble particulate carrier material which is suitable for intravenous use, which liposome precursor may be hydrated to form a liposome product of controlled and acceptable mean size, which comprises forming a solution, in an organic solvent, of at least one liposome-forming lipid selected from the group consisting of a phospholipid, a natural lecithin and a synthetic lecithin in an amount of from about 1 to about 25% by weight of the organic solution, optionally, at least one biologically active compound which is medicament, protein, enzyme, hormone or diagnostic agent, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome preparation, and coating a particulate water-soluble carrier material which is suitable for intravenous use and is substantially insoluble in said organic solvent, with the so-formed organic solution to form a thin film of liposomal components of predetermined desired amount on said carrier material which thin film contains a ratio of lipid:optional biologically active compound (where present) of within the range of from about 0.5:1 to about 1000:1, which so-coated particulate water-soluble carrier material may be exposed to a hydration medium to form a final hydrated liposome product of controlled and desired mean size.
Claim 2
Independent Claim
220 words
A method for preparing a stable liposome precursor in the form of a thin film of liposomal components of predetermined amount coated on a water-soluble particulate carrier material which is suitable for intravenous use, which liposome precursor may be hydrated to form a liposome product of controlled and acceptable mean size, which comprises forming a solution, in an organic solvent, of at least one liposome-forming lipid selected from the group consisting of a phospholipid, a natural lecithin and a synthetic lecithin in an amount of from about 1 to about 25% by weight of the organic solution, optionally, at least one biologically active compound which is medicament, protein, enzyme, hormone or diagnostic agent, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome preparation, and coating a particulate water-soluble carrier material which is suitable for intravenous use and is substantially insoluble in said organic solvent, with the so-formed organic solution to form a thin film of liposomal components of predetermined desired amount on said carrier material which thin film contains a ratio of lipid:optional biologically active compound (where present) of within the range of from about 0.5:1 to about 1000:1, which so-coated particulate water-soluble carrier material may be exposed to a hydration medium to form a final hydrated liposome product of controlled and desired mean size.
Claim 3
Dependent Claim
68 words
The method as defined in claim 1 wherein the thin film of liposomal components, coated on the particulate carrier is present in an amount within the range of from about 0.5 mg/m 2 to about 100 g/m 2 of carrier material so that the final hydrated liposome product will have a desired mean size distribution of within the range of from about 25 nm to about 12 μm.
Claim 4
Dependent Claim
32 words
The method as defined in claim 1 wherein the organic solution is formed by dissolving said lipid, optionally, said biologically active compound and, optionally, said adjuvant in one or more organic solvents.
Claim 5
Dependent Claim
36 words
The method as defined in claim 1 wherein the organic solution is formed by dissolving the optional biologically active compound and optional adjuvant in said lipid, said lipid being of the low melting point liposome-forming type.
Claim 6
Dependent Claim
35 words
The method as defined in claim 1 wherein the particulate carrier material is coated with said solution by suspending the carrier material in the solution of liposomal components and spray drying the coated carrier material.
Claim 7
Dependent Claim
13 words
The method as defined in claim 1 wherein the lipid is a phospholipid.
Claim 8
Dependent Claim
16 words
The method as defined in claim 5 wherein the phospholipid is a natural or synthetic lecithin.
Claim 9
Dependent Claim
20 words
The method as defined in claim 1 wherein the lipid is dimyristoylphosphatidyl choline, alone or in combination with dimyristoylphosphatidyl glycerol.
Claim 10
Dependent Claim
26 words
The method as defined in claim 1 wherein said solution includes a biologically active compound which is a medicament, contrast agent, enzyme, hormone, or marker compound.
Claim 11
Dependent Claim
19 words
The method as defined in claim 1 wherein the adjuvant is egg phosphatidic acid, dicetyl phosphate, or stearyl amine.
Claim 12
Dependent Claim
13 words
The method as defined in claim 1 wherein the adjuvant is a sterol.
Claim 13
Dependent Claim
28 words
The method as defined in claim 8 wherein the adjuvant also includes a sterol selected from the group consisting of cholesterol, phytosterol, ergosterol, sitosterol, sitosterol, 7-dehydrocholesterol or lanosterol.
Claim 14
Dependent Claim
17 words
The method as defined in claim 1 wherein said carrier is sodium chloride, lactose, dextrose, or sucrose.
Claim 15
Dependent Claim
45 words
The method as defined in claim 1 wherein said carrier material has a watersolubility in excess of 10% by weight, a rapid dissolution rate in water, and will form an isotonic solution in water in a concentration of from about 1 to about 10% w/v.
Claim 16
Dependent Claim
22 words
The method as defined in claim 3 wherein said carrier material is sorbitol, mannitol, or xylitol or a naturally occurring amino acid.
Claim 17
Dependent Claim
16 words
The method as defined in claim 1 wherein the carrier material is sorbitol or sodium chloride.
Claim 18
Dependent Claim
25 words
The method as defined in claim 1 wherein the organic solvent is ethanol, methanol, chloroform, dichloromethane, diethyl ether, carbon tetrachloride, ethyl acetate, dioxane or cyclohexane.
Claim 19
Dependent Claim
15 words
The method as defined in claim 14 wherein the solvent is methanol, ethanol or chloroform.
Claim 20
Dependent Claim
15 words
The method as defined in claim 1 wherein the biologically active compound is amphotericin B.
Claim 21
Dependent Claim
40 words
The method as defined in claim 1 wherein the lipid is egg lecithin, dimyristoylphosphatidyl choline alone or in admixture with dimyristoylphosphatidyl glycerol, the optional adjuvant is ergosterol, cholesterol or dicetyl phosphate, and the carrier material is sorbitol or sodium chloride.
Claim 22
Dependent Claim
18 words
The method as defined in claim 20 wherein the lipid is egg lecithin, and the adjuvant is ergosterol.
Claim 23
Dependent Claim
122 words
A stable liposome precursor which when mixed with water forms a liposome preparation of controlled and acceptable mean size distribution, comprising a water-soluble particulate carrier material suitable for intravenous use coated with a predetermined amount of a thin film of liposomal components comprised of at least one liposome-forming lipid selected from the group consisting of a phospholipid, a natural lecithin and a synthetic lecithin, optionally, at least one biologically active compound which is a medicament, protein, enzyme, hormone or diagnostic agent, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome preparation and which thin film contains a ratio of lipid:optional biologically active compound (where present) of within the range of from about 0 5:1 to about 1000:1.
Claim 24
Dependent Claim
122 words
A stable liposome precursor which when mixed with water forms a liposome preparation of controlled and acceptable mean size distribution, comprising a water-soluble particulate carrier material suitable for intravenous use coated with a predetermined amount of a thin film of liposomal components comprised of at least one liposome-forming lipid selected from the group consisting of a phospholipid, a natural lecithin and a synthetic lecithin, optionally, at least one biologically active compound which is a medicament, protein, enzyme, hormone or diagnostic agent, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome preparation and which thin film contains a ratio of lipid:optional biologically active compound (where present) of within the range of from about 0 5:1 to about 1000:1.
Claim 25
Dependent Claim
65 words
The stable liposome precursor as defined in claim 21 wherein the thin film of liposomal components is present in an amount within the range of from about 0.5 mg/m 2 to about 100 g/m 2 of carrier material so that the final hydrated liposome product will have a desired mean size distribution of within the range of from about 25 nm to about 12 μm.
Claim 26
Dependent Claim
100 words
A stable liposome precursor which when mixed with water forms a liposome preparation of controlled and acceptable mean size, comprising a water-soluble particulate carrier material suitable for intravenous coated with a predetermined amount of a thin film comprised of at least one liposome-forming lipid selected from the group consisting of a phospholipid, a natural lecithin and a synthetic lecithin, optionally, at least one biologically active compound which is a medicament, protein, enzyme, hormone or diagnostic agent, and, optionally, at least one adjuvant which imparts advantageous properties to the final liposome preparation, prepared by the method as defined in claim 1.
Claim 27
Dependent Claim
16 words
The method as defined in claim 21 including a biologically active compound which is amphotericin B.
Claim 28
Dependent Claim
14 words
The stable liposome precursor as defined in claim 22 including a biologically active compound.
Claim 29
Dependent Claim
17 words
The stable liposome precursor as defined in claim 26 wherein the biologically active compound is amphotericin B.
Claim 30
Dependent Claim
27 words
The stable liposome precursor as defined in claim 22 wherein the lipid is egg lecithin, the adjuvant is ergosterol and the biologically active compound is amphotericin B.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-05-17 | 1991-11-16 | 1992-05-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-05-17 | 1995-11-16 | 1996-05-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-05-17 | 1999-11-16 | 2000-05-17 | $7700.00 | Window Closed / Lapsed |