US4975282A
Expired / Lapsed
US
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Multilamellar liposomes having improved trapping efficiencies
Assignee: Elan Pharmaceuticals LLC
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Filing: 1987-11-17
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Granted: 1990-12-04
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Expires: 2007-11-17
Abstract
Abstract A multilamellar vesicle dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 40 percent. The vesicle can be prepared by dispersing the lipid in an aqueous phase to form a multilamellar vesicle, rapidly freezing the multilamellar vesicle to obtain a frozen lipid-aqueous medium mixture, and warming the mixture to obtain a frozen and thawed multilamellar vesicle dispersed in an aqueous phase.
Inventors
- 👤 Pieter R. Cullis
- 👤 Marcel B. Bally
- 👤 Michael J. Hope
- 👤 Andrew S. Janoff
- 👤 Lawrence D. Mayer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 20:38
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61K9/1278; A61K9/1271
Claims Analysis
Total Claims: 32
Claim 1
Independent Claim
42 words
A multilamellar vesicle having interlamellar equal solute distribution, containing a water soluble bioactive agent dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of greater than about 40 percent.
Claim 2
Dependent Claim
42 words
A multilamellar vesicle having interlamellar equal solute distribution, containing a water soluble bioactive agent dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of greater than about 40 percent.
Claim 3
Dependent Claim
25 words
The vesicle of claim 1 wherein the lipid concentration is at least about 100 mg/ml and the trapping efficiency is at least about 50 percent.
Claim 4
Dependent Claim
16 words
The vesicle of claim 2 wherein the lipid concentration is between about 100 and 1000 mg/ml.
Claim 5
Dependent Claim
16 words
The vesicle of claim 3 wherein the lipid concentration is between about 100 and 400 mg/ml.
Claim 6
Dependent Claim
22 words
The vesicle of claim 1 having an outer bilayer comprising less than about 35% of the total lipid contained in the vesicle.
Claim 7
Dependent Claim
13 words
The vesicle of claim 1 wherein the aqueous medium comprises an aqueous buffer.
Claim 8
Dependent Claim
10 words
The vesicle of claim 1 wherein the lipid comprises phospholipid.
Claim 9
Dependent Claim
10 words
The vesicle of claim 7 wherein the phospholipid comprises phosphatidylcholine.
Claim 10
Dependent Claim
12 words
The vesicle of claim 7 wherein the lipid additionally comprises a sterol.
Claim 11
Dependent Claim
10 words
The vesicle of claim 9 wherein the sterol is cholesterol.
Claim 12
Dependent Claim
110 words
A multilamellar vesicle having interlamellar equal solute distribution dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 40 percent which is prepared in the absence of organic solvent or detergents by a method comprising the steps of: (a) dispersing a lipid in an aqueous solvent to form a multilamellar vesicle; (b) rapidly freezing the multilamellar vesicle at about -70° C. to obtain a frozen lipid-aqueous medium mixture; (c) warming the mixture in a constant temperature bath to melt the aqueous medium; and (d) repeating steps (b) and (c) at least about three times.
Claim 13
Dependent Claim
110 words
A multilamellar vesicle having interlamellar equal solute distribution dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 40 percent which is prepared in the absence of organic solvent or detergents by a method comprising the steps of: (a) dispersing a lipid in an aqueous solvent to form a multilamellar vesicle; (b) rapidly freezing the multilamellar vesicle at about -70° C. to obtain a frozen lipid-aqueous medium mixture; (c) warming the mixture in a constant temperature bath to melt the aqueous medium; and (d) repeating steps (b) and (c) at least about three times.
Claim 14
Dependent Claim
14 words
The vesicle of claim 11 wherein the mixture is rapidly frozen in liquid nitrogen.
Claim 15
Dependent Claim
25 words
The vesicle of claim 11 wherein the lipid concentration is at least about 100 mg/ml and the trapping efficiency is at least about 50 percent.
Claim 16
Dependent Claim
16 words
The vesicle of claim 11 wherein the lipid concentration is between about 100 and 1000 mg/ml.
Claim 17
Dependent Claim
16 words
The vesicle of claim 11 wherein the lipid concentration is between about 100 and 400 mg/ml.
Claim 18
Dependent Claim
10 words
The vesicle of claim 11 wherein the lipid comprises phospholipid.
Claim 19
Dependent Claim
10 words
The vesicle of claim 16 wherein the phospholipid comprises phosphatidylcholine.
Claim 20
Dependent Claim
12 words
The vesicles of claim 16 wherein the lipid additionally comprises a sterol.
Claim 21
Dependent Claim
10 words
The vesicle of claim 18 wherein the sterol is cholesterol.
Claim 22
Dependent Claim
36 words
The vesicle of claim 11 which is prepared by the additional step of filtering the multilamellar vesicle dispersion under pressure through a polycarbonate filter having a pore size of about 200 nanometers to about 400 nanometers.
Claim 23
Dependent Claim
85 words
A process for preparing a multilamellar vesicle having interlamellar equal solute distribution, dispersed in an aqueous phase in the absence of organic solvent or detergents comprising the steps of: (a) dispersing a lipid in an aqueous solvent to form a multilamellar vesicle; (b) rapidly freezing the multilamellar vesicle at about -70° C. to obtain a frozen lipid-aqueous medium mixture; (c) warming the mixture in a constant temperature bath to melt the aqueous medium; and (d) repeating steps (b) and (c) at least about three times.
Claim 24
Dependent Claim
85 words
A process for preparing a multilamellar vesicle having interlamellar equal solute distribution, dispersed in an aqueous phase in the absence of organic solvent or detergents comprising the steps of: (a) dispersing a lipid in an aqueous solvent to form a multilamellar vesicle; (b) rapidly freezing the multilamellar vesicle at about -70° C. to obtain a frozen lipid-aqueous medium mixture; (c) warming the mixture in a constant temperature bath to melt the aqueous medium; and (d) repeating steps (b) and (c) at least about three times.
Claim 25
Dependent Claim
13 words
The process of claim 21 wherein liquid nitrogen is employed in Step (b).
Claim 26
Dependent Claim
15 words
The process of claim 21 comprising the additional step of concentrating the multilamellar vesicle dispersion.
Claim 27
Dependent Claim
19 words
The process of claim 21 comprising the additional step of filtering the multilamellar vesicle dispersion through a polycarbonate filter.
Claim 28
Dependent Claim
23 words
A multilamellar vesicle having interlamellar equal solute distribution, having a captured volume of at least about 1.77 ul/umol lipid, and having non-concentric bilayers.
Claim 29
Dependent Claim
23 words
A multilamellar vesicle having interlamellar equal solute distribution, having a captured volume of at least about 1.77 ul/umol lipid, and having non-concentric bilayers.
Claim 30
Dependent Claim
11 words
The multilamellar vesicle of claim 25 additionally comprising a bioactive agent.
Claim 31
Dependent Claim
12 words
The multilamellar vesicle of claim 26 wherein the bioactive agent in hydrophilic.
Claim 32
Dependent Claim
12 words
The multilamellar vesicle of claim 26 wherein the bioactive agent is lipophilic.
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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) | 1993-12-03 | 1994-06-04 | 1994-12-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-12-03 | 1998-06-04 | 1998-12-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-12-03 | 2002-06-04 | 2002-12-04 | $7700.00 | Window Closed / Lapsed |