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US4933121A
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Process for forming liposomes
Assignee: Bayer Corp
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Filing: 1988-07-25
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Granted: 1990-06-12
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Expires: 2008-07-25
Abstract
Abstract The present invention relates to a process for forming stable, uniform unilamellar or oligolamellar liposomes which encapsulate a macromolecule. However, unlike prior processes, the present method maintains a temperature below the phase transition temperature of the lipid used to make the liposome both during the hydration of the lipid and, if used, during an extrusion step. In addition, the liposome is formed and the macromolecule encapsulated in a low ionic strength solution, then they are dialyzed against a high ionic strength solution.
Inventors
- 👤 Say-Jong Law
- 👤 Uri Piran
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 05:53
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; Y; Y10; Y10S; Y10S436/00; Y10S436/829
Claims Analysis
Total Claims: 8
Claim 1
Independent Claim
118 words
A process for forming unilamellar or oligolamellar liposomes which encapsulate a macromolecule comprising: a. forming a lipid film which lipid film comprises a phospholipid with a phase-transition temperature greater than about 31° C; and b. hydrating the lipid film in the presence of a macromolecule to be encapsulated at a temperature between about 31° C and 42° C, said temperature of hydration being below the phase-transition temperature of the phospholipid, to form a liposome suspension, and wherein the lipsome suspension is extruded so as to form liposomes having a desired size, said extrusion occurring at a temperature between 37° C and 42° C, said temperature of extrusion being below the phase-transition temperature of the phospholipid of the liposomes.
Claim 2
Dependent Claim
118 words
A process for forming unilamellar or oligolamellar liposomes which encapsulate a macromolecule comprising: a. forming a lipid film which lipid film comprises a phospholipid with a phase-transition temperature greater than about 31° C; and b. hydrating the lipid film in the presence of a macromolecule to be encapsulated at a temperature between about 31° C and 42° C, said temperature of hydration being below the phase-transition temperature of the phospholipid, to form a liposome suspension, and wherein the lipsome suspension is extruded so as to form liposomes having a desired size, said extrusion occurring at a temperature between 37° C and 42° C, said temperature of extrusion being below the phase-transition temperature of the phospholipid of the liposomes.
Claim 3
Dependent Claim
17 words
A process as recited in claim 1, wherein the phospholipid has fully saturated fatty acid radical substituents.
Claim 4
Dependent Claim
20 words
The process as recited in claim 1, wherein the phospholipid comprises a mixture of dipalmitoyl phosphatidylcholine, dipalmitoyl phosphatidylglycerol and cholesterol.
Claim 5
Dependent Claim
13 words
A process as recited in claim 1, wherein the macromolecule is a protein.
Claim 6
Dependent Claim
13 words
A process as recited in claim 4, wherein the protein is an enzyme.
Claim 7
Dependent Claim
46 words
The process as recited in claim 1, wherein the liposome is extruded through a membrane means at less than 500 psi, the membrane means having at least two sequentially smaller porosity membranes, the final membrane having a porosity equal to the desired size of the liposome.
Claim 8
Dependent Claim
19 words
The process as recited in claim 1, wherein the extrusion step is performed at pressure less than 200 psi.
References Cited (Backward Citations)
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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) | 1993-06-11 | 1993-12-11 | 1994-06-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-06-11 | 1997-12-11 | 1998-06-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-06-11 | 2001-12-11 | 2002-06-12 | $7700.00 | Window Closed / Lapsed |