US4235871A
Expired / Lapsed
US
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Method of encapsulating biologically active materials in lipid vesicles
Assignee: Liposome Technology Inc
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Filing: 1978-02-24
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Granted: 1980-11-25
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Expires: 1998-02-24
Abstract
Abstract The disclosure is of a method for encapsulating biologically active materials in synthetic, oligolamellar lipid vesicles (liposomes). The method comprises providing a mixture of lipid in organic solvent and an aqueous mixture of the material for encapsulation, emulsifying the provided mixture, removing the organic solvent and suspending the resultant gel in water. The method of the invention is advantageous over prior art methods of encapsulating biologically active materials in that it provides a means for a relatively high capture efficiency of the material for encapsulation. The disclosure is also of intermediate compositions in the encapsulation method, the product vesicles, compositions including the product vesicles as an active ingredient and their use.
Inventors
- 👤 Demetrios P. Papahadjopoulos
- 👤 Francis C. Szoka, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 11:39
CPC Classifications
C; C12; C12N; C12N1/00; C12N1/04; A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; C12N15/00; C12N15/09; C12N15/87; C12N15/88; C12N9/00; C12N9/98; Y; Y10; Y10S; Y10S424/00; Y10S424/812; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
120 words
A method of encapsulating biologically active materials in synthetic, oligolamellar, lipid vesicles, which comprises: providing a mixture of a vesicle wall forming compound in organic solvent and an aqueous mixture of the biologically active material to be encapsulated, the ratio of organic phase to aqueous phase being that which will produce an emulsion of the water-in-oil type; forming a homogeneous water-in-oil type of emulsion of said mixture; evaporating organic solvent from the emulsion, until a mixture is obtained having a gel-like character; and converting the gel-like mixture to a suspension of synthetic, oligolamellar vesicles encapsulating the biologically active material by one of the steps of (a) agitating said gel-like mixture and (b) dispersing said gel-like mixture in an aqueous media.
Claim 2
Independent Claim
120 words
A method of encapsulating biologically active materials in synthetic, oligolamellar, lipid vesicles, which comprises: providing a mixture of a vesicle wall forming compound in organic solvent and an aqueous mixture of the biologically active material to be encapsulated, the ratio of organic phase to aqueous phase being that which will produce an emulsion of the water-in-oil type; forming a homogeneous water-in-oil type of emulsion of said mixture; evaporating organic solvent from the emulsion, until a mixture is obtained having a gel-like character; and converting the gel-like mixture to a suspension of synthetic, oligolamellar vesicles encapsulating the biologically active material by one of the steps of (a) agitating said gel-like mixture and (b) dispersing said gel-like mixture in an aqueous media.
Claim 3
Dependent Claim
13 words
The method of claim 1 wherein the wall forming compound is a phospholipid.
Claim 4
Dependent Claim
18 words
The method of claim 2 wherein the phospholipid comprises phosphatidylcholine in admixture with a second phospholipid and cholesterol.
Claim 5
Dependent Claim
20 words
The method of claim 3 wherein the proportion of phosphatidylcholine is in a ratio of 4:1 to the second phospholipid.
Claim 6
Dependent Claim
35 words
The method of claim 1 wherein the wall forming compound is initially provided in an inert solvent and is then deposited on the side wall of a reaction vessel by evaporation of the inert solvent.
Claim 7
Dependent Claim
23 words
The method of claim 1 wherein the organic solvent is selected from the group consisting of diethyl ether, chloroform, tetrahydrofuran and isopropyl ether.
Claim 8
Dependent Claim
23 words
The method of claim 1 wherein the aqueous mixture is buffered to a pH suitable to maintain stability of the biologically active material.
Claim 9
Dependent Claim
20 words
The method of claim 7 wherein the buffer is an ionic compound, at a strength of less than 0.3 units.
Claim 10
Dependent Claim
31 words
The method of claim 1 wherein the proportion of wall forming compound is within the range of from about 0.5 mg to about 50 mg per milliliter of the organic solvent.
Claim 11
Dependent Claim
24 words
The method of claim 1 wherein emulsification is carried out with ultrasonic radiation at a temperature of from about -10° to about 50° C.
Claim 12
Dependent Claim
11 words
The method of claim 1 carried out under an inert atmosphere.
Claim 13
Dependent Claim
24 words
The method of claim 1 wherein the aqueous mixture comprises water buffered to a pH suitable to maintain stability of the biologically active material.
Claim 14
Dependent Claim
17 words
The method of claim 1 wherein the oligolamellar vesicles are then separated from unencapsulated biologically active materials.
Claim 15
Dependent Claim
13 words
The method of claim 1 wherein the biologically active material is an enzyme.
Claim 16
Dependent Claim
13 words
The method of claim 1 wherein the biologically active material is an antibiotic.
Claim 17
Dependent Claim
14 words
The method of claim 1 wherein the biologically active material is a nucleic acid.
Claim 18
Dependent Claim
13 words
The method of claim 16 wherein the nucleic acid is a deoxyribonucleic acid.
Claim 19
Dependent Claim
13 words
The method of claim 1 wherein the biologically active material is a pesticide.
Claim 20
Dependent Claim
13 words
The method of claim 1 wherein the biologically active material is a polypeptide.
Claim 21
Dependent Claim
10 words
The method of claim 19 wherein the polypeptide is insulin.
Claim 22
Dependent Claim
14 words
The method of claim 1 wherein the biologically active material is a bacterial organism.
Claim 23
Dependent Claim
13 words
The method of claim 1 wherein the biologically active material is a virus.
Claim 24
Dependent Claim
25 words
The method of claim 1 wherein the wall forming compound is a mixture of cholesterol, phosphatidyglycerol and phosphatidylcholine in a ratio of 5:1:4 by weight.
Claim 25
Dependent Claim
8 words
The product of the process of claim 1.
Claim 26
Dependent Claim
26 words
The method of claim 1 wherein the ratio of organic phase to aqueous phase is within the range of from about 2:1 to about 20:1 v/v.
Claim 27
Dependent Claim
10 words
The method of claim 25 wherein said ratio is 4:1.
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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) | 1983-11-25 | 1984-05-26 | 1984-11-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-11-25 | 1988-05-26 | 1988-11-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-11-25 | 1992-05-26 | 1992-11-25 | $7700.00 | Window Closed / Lapsed |