US4911928A
Expired / Lapsed
US
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Paucilamellar lipid vesicles
Assignee: Novavax Inc
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Filing: 1988-03-03
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Granted: 1990-03-27
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Expires: 2008-03-03
Abstract
Abstract A new method of producing paucilamellar lipid vesicles has been developed. The vesicles are made of non-phospholipid surfactants. The paucilamellar lipid vesicles have 2-8 lipid bilayers surrounding a central cavity which may be filled with either an aqueous-based solution or an oil or wax.
Inventors
- 👤 Donald F. H. Wallach
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 05:03
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272; A61K9/1277; C; C11; C11D; C11D17/00; C11D17/0008; C11D17/0017; C11D17/0021; C11D17/0026; Y; Y10; Y10S; Y10S424/00; Y10S424/10; Y10S424/812; Y10S436/00; Y10S436/829; Y10S525/00; Y10S525/936; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
348 words
A method of making paucilamellar lipid vesicles having a water immiscible oily material filling a substantial portion of the amorphous central cavity comprising the steps of: A. forming a lipid phase of a surfactant and any lipid soluble materials to be incorporated into said lipid vesicles, said surfactant being selected from a group consisting of polyoxyethylene fatty esters having the formula R.sub.1 --COO(C.sub.2 H.sub.4 O).sub.n H where R 1 is lauric, myristic, cetyl, stearic, or oleic acid, or their derivatives and n=2-10; polyoxyethylene fatty acid ethers, having the formula R.sub.2 --CO(C.sub.2 H.sub.4)).sub.m H where R 2 is lauric, myristic, or cetyl acids or their derivatives, single or double unsaturated octadecyl acids or their derivative, or double unsaturated eicodienoic acids or their derivatives and m ranges from 2-4; diethanolamides, having the formula (HOCH.sub.2 --CH.sub.2).sub.2 NCO--R.sub.3 where R 3 is caprylic, lauric, myristic or linoleic acids or their derivatives; long chain acyl hexosamides having the formula R.sub.4 --NHCO--(CH.sub.2).sub.3 --CH.sub.3 where b ranges from 10-18 and R 4 is a sugar molecule selected from a group consisting of glucosamine, glactosmaine, and N-methylglucamine; long chain acyl amino acid amides having the formula R.sub.5 --CH(COOH)--NHCO--(CH.sub.2).sub.c --CH.sub.3 where c ranges from 10-18 and R 5 is an amino acid side chain; long chain acyl amides having the formula HOOC--(CH.sub.2).sub.d --N(CH.sub.3)--(CH.sub.2).sub.3 --NHCO--R.sub.6 where R 6 is an acyl chain having 12-20 carbons and not more than two unsaturations, and d ranges from 1-3; polyoxyethylene (20) sorbitan mono- or trioletate; polyoxyethylene glyceryl monosterate with 1-10 polyoxyethylene groups; and glycerol monosterate; B. forming an oily phase of water immiscible oily material and an oil-suspendable or oil-soluble material to be incorporated; C. forming a lipophilic phase by dispersing said oily phase in said lipid phase; D. forming an aqueous phase of an aqueous solution and any aqueous soluble material to be incorporated into said lipid vesicles; E. blending said lipophilic phase and said aqueous phase under shear mixing conditions thereby forming said paucilamellar lipid vesicles having about 2-8 exterior lipid bilayers surrounding a substantially amorphous center with said water immiscible oily material substantially filling said amorphous central cavity.
Claim 2
Independent Claim
348 words
A method of making paucilamellar lipid vesicles having a water immiscible oily material filling a substantial portion of the amorphous central cavity comprising the steps of: A. forming a lipid phase of a surfactant and any lipid soluble materials to be incorporated into said lipid vesicles, said surfactant being selected from a group consisting of polyoxyethylene fatty esters having the formula R.sub.1 --COO(C.sub.2 H.sub.4 O).sub.n H where R 1 is lauric, myristic, cetyl, stearic, or oleic acid, or their derivatives and n=2-10; polyoxyethylene fatty acid ethers, having the formula R.sub.2 --CO(C.sub.2 H.sub.4)).sub.m H where R 2 is lauric, myristic, or cetyl acids or their derivatives, single or double unsaturated octadecyl acids or their derivative, or double unsaturated eicodienoic acids or their derivatives and m ranges from 2-4; diethanolamides, having the formula (HOCH.sub.2 --CH.sub.2).sub.2 NCO--R.sub.3 where R 3 is caprylic, lauric, myristic or linoleic acids or their derivatives; long chain acyl hexosamides having the formula R.sub.4 --NHCO--(CH.sub.2).sub.3 --CH.sub.3 where b ranges from 10-18 and R 4 is a sugar molecule selected from a group consisting of glucosamine, glactosmaine, and N-methylglucamine; long chain acyl amino acid amides having the formula R.sub.5 --CH(COOH)--NHCO--(CH.sub.2).sub.c --CH.sub.3 where c ranges from 10-18 and R 5 is an amino acid side chain; long chain acyl amides having the formula HOOC--(CH.sub.2).sub.d --N(CH.sub.3)--(CH.sub.2).sub.3 --NHCO--R.sub.6 where R 6 is an acyl chain having 12-20 carbons and not more than two unsaturations, and d ranges from 1-3; polyoxyethylene (20) sorbitan mono- or trioletate; polyoxyethylene glyceryl monosterate with 1-10 polyoxyethylene groups; and glycerol monosterate; B. forming an oily phase of water immiscible oily material and an oil-suspendable or oil-soluble material to be incorporated; C. forming a lipophilic phase by dispersing said oily phase in said lipid phase; D. forming an aqueous phase of an aqueous solution and any aqueous soluble material to be incorporated into said lipid vesicles; E. blending said lipophilic phase and said aqueous phase under shear mixing conditions thereby forming said paucilamellar lipid vesicles having about 2-8 exterior lipid bilayers surrounding a substantially amorphous center with said water immiscible oily material substantially filling said amorphous central cavity.
Claim 3
Dependent Claim
24 words
The method of claim 1 wherein said oily material has an oil-suspendable or oil-soluble material to be encapsulated in said lipid vesicle dispersed therein.
Claim 4
Dependent Claim
13 words
The method of claim 1 wherein said lipophilic phase further comprises a steroid.
Claim 5
Dependent Claim
24 words
The method of claim 3 wherein said steroid comprises a sterol selected from a group consisting of cholesterol, hydrocortisone, and analogues and derivatives thereof.
Claim 6
Dependent Claim
14 words
The method of claim 1 wherein said lipophilic phase further comprises a charge-producing agent.
Claim 7
Dependent Claim
33 words
The method of claim 5 wherein said charge-producing agent is a negative charge-producing agent selected from a group consisting of oleic acid, dicetyl phosphate, cetyl sulphate, phosphatidic acid, phosphatidyl serine, and mixtures thereof.
Claim 8
Dependent Claim
257 words
Oil filled paucilamellar lipid vesicles consisting of about 2-8 lipid bilayers in the form of substantially spherical shells separated by aqueous layers, said lipid bilayers surrounding a large, substantially oil filled amorphous central cavity, said lipid bilayers comprising a surfactant selected from a group consisting of polyoxyethylene fatty esters having the formula R.sub.1 --COO(C.sub.2 H.sub.4 O).sub.n H where R 1 is lauric, myristic, cetyl, stearic, or oleic acid, or their derivatives and n=2-10; polyoxyethylene fatty acid ethers, having the formula R.sub.2 --CO(C.sub.2 H.sub.4 O).sub.m H where R 2 is lauric, myristic, or cetyl acids of their derivatives, single or double unsaturated octadecyl acids or their derivative, or double unsaturated eicodienoic acids or their derivatives and m ranges from 2-4; diethanolamides, having the formula (HOCH.sub.2 --CH.sub.2).sub.2 NCO--R.sub.3 where R 3 is caprylic, lauric, myristic or linoleic acids or their derivatives; long chain acyl hexosamides having the formula R.sub.4 --NHCO--(CH.sub.2).sub.3 --CH.sub.3 where b ranges from 10-18 and R 4 is a sugar molecule selected from a group consisting of glucosamine, galactomsamine, and N-methylglucamine; long chain acyl amino acid amides having the formula R.sub.5 --CH(COOH)--NHCO--(CH.sub.2).sub.c --CH.sub.3 where c ranges from 10-18 and R 5 is an amino acid side chain; long chain acyl amides having the formula HOOC--(CH.sub.2).sub.d --N--(CH.sub.3)--(CH.sub.2).sub.3 --NHCO--R.sub.6 where R 6 is an acyl chain having 12-20 carbons and not more than two unsaturations, and d ranges from 1-3; polyoxyethylene (20) sorbitan mono- or trioleate; polyoxyethylene glyceryl monosterate with 1-10 polyoxyethylene groups; and glycerol monostearate; said amorphous central cavity being substantially filled with a water immiscible oily solution.
Claim 9
Dependent Claim
257 words
Oil filled paucilamellar lipid vesicles consisting of about 2-8 lipid bilayers in the form of substantially spherical shells separated by aqueous layers, said lipid bilayers surrounding a large, substantially oil filled amorphous central cavity, said lipid bilayers comprising a surfactant selected from a group consisting of polyoxyethylene fatty esters having the formula R.sub.1 --COO(C.sub.2 H.sub.4 O).sub.n H where R 1 is lauric, myristic, cetyl, stearic, or oleic acid, or their derivatives and n=2-10; polyoxyethylene fatty acid ethers, having the formula R.sub.2 --CO(C.sub.2 H.sub.4 O).sub.m H where R 2 is lauric, myristic, or cetyl acids of their derivatives, single or double unsaturated octadecyl acids or their derivative, or double unsaturated eicodienoic acids or their derivatives and m ranges from 2-4; diethanolamides, having the formula (HOCH.sub.2 --CH.sub.2).sub.2 NCO--R.sub.3 where R 3 is caprylic, lauric, myristic or linoleic acids or their derivatives; long chain acyl hexosamides having the formula R.sub.4 --NHCO--(CH.sub.2).sub.3 --CH.sub.3 where b ranges from 10-18 and R 4 is a sugar molecule selected from a group consisting of glucosamine, galactomsamine, and N-methylglucamine; long chain acyl amino acid amides having the formula R.sub.5 --CH(COOH)--NHCO--(CH.sub.2).sub.c --CH.sub.3 where c ranges from 10-18 and R 5 is an amino acid side chain; long chain acyl amides having the formula HOOC--(CH.sub.2).sub.d --N--(CH.sub.3)--(CH.sub.2).sub.3 --NHCO--R.sub.6 where R 6 is an acyl chain having 12-20 carbons and not more than two unsaturations, and d ranges from 1-3; polyoxyethylene (20) sorbitan mono- or trioleate; polyoxyethylene glyceryl monosterate with 1-10 polyoxyethylene groups; and glycerol monostearate; said amorphous central cavity being substantially filled with a water immiscible oily solution.
Claim 10
Dependent Claim
36 words
The paucilamellar lipid vesicles of claim 7 wherein said water immiscible oily solution is selected from a group consisting of oils, waxes, natural and synthetic triglycerides, acyl esters, and petroleum derivatives, and their analogues and derivatives.
Claim 11
Dependent Claim
15 words
The paucilamellar lipid vesicles of claim 8 wherein said lipid bilayers further comprise a steroid.
Claim 12
Dependent Claim
24 words
The paucilamellar lipid vesicles of claim 9 wherein said steroid is selected from a group consisting of cholesterol, hydrocortisone, and analogues and derivatives thereof.
Claim 13
Dependent Claim
16 words
The paucilamellar lipid vesicles of claim 8 wherein said lipid bilayers further comprise a charge-producing agent.
Claim 14
Dependent Claim
31 words
The paucilamellar lipid vesicles of claim 11 wherein said charge-producing agent is selected from a group consisting of oleic acid, dicetyl phosphate, cetyl sulphate, phosphatidic acid, phosphatidyl serine, and mixtures thereof.
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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) | 1993-03-26 | 1993-09-25 | 1994-03-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-03-26 | 1997-09-25 | 1998-03-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-03-26 | 2001-09-25 | 2002-03-27 | $7700.00 | Window Closed / Lapsed |