Patent US4921706A successfully refreshed from Google Patents.
US4921706A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Unilamellar lipid vesicles and method for their formation
Assignee: Massachusetts Institute of Technology
•
Filing: 1984-11-20
•
Granted: 1990-05-01
•
Expires: 2004-11-20
Abstract
Abstract This invention relates to unilamellar lipid vesicles comprised of short-chain phospholipids and long-chain phospholipids and a method for making the vesicles. The short-chain phospholipids are comprised of fatty acids with fewer than 9 carbons atoms and the long-chain phospholipids are comprised of fatty acids with at least 12 carbon atoms.
Inventors
- 👤 Mary P. Roberts
- 👤 Nancy E. Gabriel
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 18:27
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; Y; Y10; Y10S; Y10S436/00; Y10S436/829; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
75 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with 6 to 8 carbon atoms and long chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent; (b) removing organic solvent from the solution to form a residue; (c) dispersing the residue in an aqueous medium; and (d) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 2
Independent Claim
75 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with 6 to 8 carbon atoms and long chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent; (b) removing organic solvent from the solution to form a residue; (c) dispersing the residue in an aqueous medium; and (d) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 3
Dependent Claim
9 words
The vesicle produced by the method of claim 1.
Claim 4
Dependent Claim
34 words
The method of claim 1 additionally incorporating into the solution of short-chain phospholipids and long-chain phospholipids at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine.
Claim 5
Dependent Claim
9 words
The vesicle produced by the method of claim 3.
Claim 6
Independent Claim
64 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short chain phospholipids having fatty acids with 6 to 8 carbon atoms and of long-chain phospholipids having fatty acids with at least 12 carbon atoms; (b) dispersing the film in an aqueous medium; and (c) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 7
Independent Claim
64 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short chain phospholipids having fatty acids with 6 to 8 carbon atoms and of long-chain phospholipids having fatty acids with at least 12 carbon atoms; (b) dispersing the film in an aqueous medium; and (c) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 8
Dependent Claim
9 words
The vesicle produced by the method of claim 5.
Claim 9
Independent Claim
80 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short-chain phospholipids having fatty acids with 6 to 8 carbon atoms; long-chain phospholipids having fatty acids with at least 12 carbon atoms and at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid; cardiolipin and lysophosphatidylcholine; (b) dispersing the film in an aqueous medium; and (c) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 10
Independent Claim
80 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short-chain phospholipids having fatty acids with 6 to 8 carbon atoms; long-chain phospholipids having fatty acids with at least 12 carbon atoms and at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid; cardiolipin and lysophosphatidylcholine; (b) dispersing the film in an aqueous medium; and (c) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 11
Dependent Claim
9 words
The vesicle produced by the method of claim 7.
Claim 12
Independent Claim
82 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) dissolving short-chain phospholipids having fatty acids with fewer than 9 carbon atoms and long-chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent to form a solution thereof; (b) evaporating the organic solvent under nitrogen to form a film of short-chain phospholipids and long-chain phospholipids; (c) dispersing the film in an aqueous medium; and (d) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 13
Independent Claim
82 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) dissolving short-chain phospholipids having fatty acids with fewer than 9 carbon atoms and long-chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent to form a solution thereof; (b) evaporating the organic solvent under nitrogen to form a film of short-chain phospholipids and long-chain phospholipids; (c) dispersing the film in an aqueous medium; and (d) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 14
Dependent Claim
19 words
The method of claim 9 in which the short-chain phospholipids have fatty acids with 6 to 8 carbon atoms.
Claim 15
Dependent Claim
9 words
The vesicle produced by the method of claim 10.
Claim 16
Dependent Claim
38 words
The method of claim 10, additionally incorporating into the solution of short-chain phospholipids and long-chain phospholipids in an organic solvent at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine.
Claim 17
Dependent Claim
9 words
The vesicle produced by the method of claim 12.
Claim 18
Independent Claim
113 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in organic solvent; (b) removing organic solvent to produce a first residue; (c) dispersing the first residue in an aqueous medium; (d) forming a solution of long-chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent; (e) removing organic solvent to produce a second residue; (f) dispersing the second residue in an aqueous medium; (g) combining the dispersion of the first residue and the dispersion of the second residue; and (h) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 19
Independent Claim
113 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in organic solvent; (b) removing organic solvent to produce a first residue; (c) dispersing the first residue in an aqueous medium; (d) forming a solution of long-chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent; (e) removing organic solvent to produce a second residue; (f) dispersing the second residue in an aqueous medium; (g) combining the dispersion of the first residue and the dispersion of the second residue; and (h) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 20
Dependent Claim
21 words
The method of claim 14 in which the short-chain phospholipids are comprised of fatty acids having 6 to 8 carbon atoms.
Claim 21
Dependent Claim
9 words
The vesicle produced by the method of claim 14.
Claim 22
Dependent Claim
35 words
The method of claim 15, additionally incorporating into the solution of long-chain phospholipids in an organic solvent at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine.
Claim 23
Dependent Claim
9 words
The vesicle produced by the method of claim 17.
Claim 24
Independent Claim
93 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms; (b) dispersing the film of short-chain phospholipids in an aqueous medium; (c) forming a film of long-chain phospholipids having fatty acids with at least 12 carbon atoms; (d) dispersing the film of long-chain phospholipids in an aqueous medium; (e) combining the dispersion of short-chain phospholipids and the dispersion of long-chain phospholipids; and (f) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 25
Independent Claim
93 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms; (b) dispersing the film of short-chain phospholipids in an aqueous medium; (c) forming a film of long-chain phospholipids having fatty acids with at least 12 carbon atoms; (d) dispersing the film of long-chain phospholipids in an aqueous medium; (e) combining the dispersion of short-chain phospholipids and the dispersion of long-chain phospholipids; and (f) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 26
Dependent Claim
21 words
The method of claim 19 in which the short-chain phospholipids are comprised of fatty acids having 6 to 8 carbon atoms.
Claim 27
Dependent Claim
9 words
The vesicle produced by the method of claim 19.
Claim 28
Independent Claim
124 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms; (b) dispersing the film of short-chain phospholipids in an aqueous medium to form a first dispersion; (c) forming a film of long-chain phospholipids having fatty acids with at least 12 carbon atoms and at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine; (d) dispersing the film of long-chain phospholipids and at least one additional component in an aqueous medium to form a second dispersion; (e) combining the first dispersion and the second dispersion; and (f) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 29
Independent Claim
124 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a film of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms; (b) dispersing the film of short-chain phospholipids in an aqueous medium to form a first dispersion; (c) forming a film of long-chain phospholipids having fatty acids with at least 12 carbon atoms and at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine; (d) dispersing the film of long-chain phospholipids and at least one additional component in an aqueous medium to form a second dispersion; (e) combining the first dispersion and the second dispersion; and (f) equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 30
Dependent Claim
21 words
The method of claim 22 in which the short-chain phospholipids are comprised of fatty acids having 6 to 8 carbon atoms.
Claim 31
Dependent Claim
9 words
The vesicle produced by the method of claim 22.
Claim 32
Independent Claim
126 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in an organic solvent; (b) evaporating the organic solvent under nitrogen to form a film of short-chain phospholipids; (c) dispersing the film of short-chain phospholipids in an aqueous medium; (d) forming a solution of long-chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent; (e) evaporating the organic solvent under nitrogen to form a film of long-chain phospholipids; (f) dispersing the film of long-chain phospholipids in an aqueous medium; (g) combining the dispersion of short-chain phospholipids and the dispersion of long-chain phospholipids; and (h) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 33
Independent Claim
126 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in an organic solvent; (b) evaporating the organic solvent under nitrogen to form a film of short-chain phospholipids; (c) dispersing the film of short-chain phospholipids in an aqueous medium; (d) forming a solution of long-chain phospholipids having fatty acids with at least 12 carbon atoms in an organic solvent; (e) evaporating the organic solvent under nitrogen to form a film of long-chain phospholipids; (f) dispersing the film of long-chain phospholipids in an aqueous medium; (g) combining the dispersion of short-chain phospholipids and the dispersion of long-chain phospholipids; and (h) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 34
Dependent Claim
21 words
The method of claim 25 in which the short-chain phospholipids are comprised of fatty acids having 6 to 8 carbon atoms.
Claim 35
Dependent Claim
9 words
The vesicle produced by the method of claim 25.
Claim 36
Independent Claim
139 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in an organic solvent; (b) evaporating the organic solvent under nitrogen to form a first film; (c) dispersing the first film in an aqueous medium; (d) forming a solution of long-chain phospholipids having fatty acids with at least 12 carbon atoms and at least one additional component selected from the group consisting of cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine in an organic solvent; (e) evaporating the organic solvent under nitrogen to form a second film; (f) dispersing the second film in an aqueous medium; (g) combining the dispersion of the first film and the dispersion of the second film; and (h) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 37
Independent Claim
139 words
A method of forming unilamellar lipid vesicles, comprising the steps of: (a) forming a solution of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in an organic solvent; (b) evaporating the organic solvent under nitrogen to form a first film; (c) dispersing the first film in an aqueous medium; (d) forming a solution of long-chain phospholipids having fatty acids with at least 12 carbon atoms and at least one additional component selected from the group consisting of cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysophosphatidylcholine in an organic solvent; (e) evaporating the organic solvent under nitrogen to form a second film; (f) dispersing the second film in an aqueous medium; (g) combining the dispersion of the first film and the dispersion of the second film; and (h) equilibrating the resulting dispersion until unilamellar lipid vesicles have formed.
Claim 38
Dependent Claim
21 words
The method of claim 28 in which the short-chain phospholipids are comprised of fatty acids having 6 to 8 carbon atoms.
Claim 39
Dependent Claim
9 words
The vesicle produced by the method of claim 29.
Claim 40
Dependent Claim
29 words
A unilamellar lipid vesicle comprised of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms and long-chain phospholipids having fatty acids with at least 12 carbon atoms.
Claim 41
Dependent Claim
29 words
A unilamellar lipid vesicle comprised of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms and long-chain phospholipids having fatty acids with at least 12 carbon atoms.
Claim 42
Dependent Claim
23 words
The unilamellar lipid vesicle of claim 31 in which the short-chain phospholipids are comprised of fatty acids having 6 to 8 carbon atoms.
Claim 43
Dependent Claim
44 words
A composition for the delivery of a substance comprising a unilamellar lipid vesicle of short-chain phospholipids comprised of fatty acids having 6-8 carbon atoms and long-chain phospholipids comprised of fatty acids having at least 12 carbon atoms, said unilamellar lipid vesicle encapsulating the substance.
Claim 44
Dependent Claim
44 words
A composition for the delivery of a substance comprising a unilamellar lipid vesicle of short-chain phospholipids comprised of fatty acids having 6-8 carbon atoms and long-chain phospholipids comprised of fatty acids having at least 12 carbon atoms, said unilamellar lipid vesicle encapsulating the substance.
Claim 45
Dependent Claim
15 words
A unilamellar lipid vesicle of claim 33 in which the encapsulated substance is a drug.
Claim 46
Dependent Claim
65 words
In a method of forming unilamellar lipid vesicles, the improvement comprising combining a dispersion of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in a first aqueous medium and a dispersion of long-chain phospholipids having fatty acids with at least 12 carbon atoms in a second aqueous medium and equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 47
Dependent Claim
65 words
In a method of forming unilamellar lipid vesicles, the improvement comprising combining a dispersion of short-chain phospholipids having fatty acids with fewer than 9 carbon atoms in a first aqueous medium and a dispersion of long-chain phospholipids having fatty acids with at least 12 carbon atoms in a second aqueous medium and equilibrating the resulting dispersion under conditions suitable for unilamellar lipid vesicles to form.
Claim 48
Dependent Claim
47 words
A unilamellar lipid vesicle comprised of short-chain phospholipids comprised of fatty acids having 6-8 carbon atoms, long-chain phospholipids comprised of fatty acids having at least 12 carbon atoms, and at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysopholsphatidylcholine.
Claim 49
Dependent Claim
47 words
A unilamellar lipid vesicle comprised of short-chain phospholipids comprised of fatty acids having 6-8 carbon atoms, long-chain phospholipids comprised of fatty acids having at least 12 carbon atoms, and at least one additional component selected from the group consisting of: cholesterol, stearylamine, phosphatidic acid, cardiolipin and lysopholsphatidylcholine.
Claim 50
Dependent Claim
39 words
Unilamellar lipid vesicles having a single lipid bilayer which is comprised of: (a) short-chain phospholipids selected from the group consisting of dihexanoylphosphatidylcholine, diheptanoylphosphatidylcholine and dioctanoylphosphatidylcholine; and (b) long-chain phospholipids comprised of fatty acids having at least 12 carbon atoms.
Claim 51
Dependent Claim
39 words
Unilamellar lipid vesicles having a single lipid bilayer which is comprised of: (a) short-chain phospholipids selected from the group consisting of dihexanoylphosphatidylcholine, diheptanoylphosphatidylcholine and dioctanoylphosphatidylcholine; and (b) long-chain phospholipids comprised of fatty acids having at least 12 carbon atoms.
References Cited (Backward Citations)
US4427649A
Cited
US4217344A
Cited
US4224179A
Cited
US4263286A
Cited
US4310506A
Cited
US4372949A
Cited
US4310505A
Cited
EP0088046A2
Cited
US4515736A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-04-30 | 1993-10-30 | 1994-05-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-04-30 | 1997-10-30 | 1998-05-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-04-30 | 2001-10-30 | 2002-05-01 | $7700.00 | Window Closed / Lapsed |