US4855090A
Expired / Lapsed
US
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Method of producing high aqueous volume multilamellar vesicles
Assignee: IGEN Inc A DE CORP
•
Filing: 1987-07-28
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Granted: 1989-08-08
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Expires: 2007-07-28
Abstract
Abstract Disclosed is a new method of producing high aqueous volume multilamellar lipid vesicles. The method uses less expensive materials than those commonly used, is faster than classical methods, and produces vesicles with a much higher encapsulated mass and captured volume than was previously available.
Inventors
- 👤 Donald F. H. Wallach
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 21:27
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61K9/1271; A61K9/1272; C; C11; C11D; C11D17/00; C11D17/0008; C11D17/0017; C11D17/0021; C11D17/0026; Y; Y10; Y10S; Y10S424/00; Y10S424/812; Y10S436/00; Y10S436/829; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
129 words
A method of preparing high aqueous volume multilamellar lipid vesicles consisting essentially of the steps of: A. Providing a solventless non-aqueous liphphilic phase by blending a polyoxyethylene fatty ether surfactant with a sterol and a charge producing amphiphile while maintaining the temperature of said lipophilic phase above the melting point of said surfactant; B. Providing an aqueous phase formed of an aqueous solvent and any aqueous soluble materials to be encapsulated; and C. Combining said non-aqueous lipophilic phase with a substantial excess of said aqueous phase in a single step under shear conditions while maintaining the temperature of the mixture above the melting point of said surfactant; whereby said high aqueous volume multilamellar lipid vesicles are formed in less than two minutes without forming a separable hydrated lamellar phase.
Claim 2
Independent Claim
129 words
A method of preparing high aqueous volume multilamellar lipid vesicles consisting essentially of the steps of: A. Providing a solventless non-aqueous liphphilic phase by blending a polyoxyethylene fatty ether surfactant with a sterol and a charge producing amphiphile while maintaining the temperature of said lipophilic phase above the melting point of said surfactant; B. Providing an aqueous phase formed of an aqueous solvent and any aqueous soluble materials to be encapsulated; and C. Combining said non-aqueous lipophilic phase with a substantial excess of said aqueous phase in a single step under shear conditions while maintaining the temperature of the mixture above the melting point of said surfactant; whereby said high aqueous volume multilamellar lipid vesicles are formed in less than two minutes without forming a separable hydrated lamellar phase.
Claim 3
Dependent Claim
45 words
The method of claim 1 wherein said surfactant comprises a polyoxyethylene fatty ether having the structure R.sub.1 --O--(CH.sub.2 --CH.sub.2 CH.sub.2 --O--).sub.m --H where R 1 is CH 3 --CH 2 ) n , n ranges from 11 to 15, and m is 2 to 4.
Claim 4
Dependent Claim
14 words
The method of claim 2 wherein said sterol comprises cholesterol or a derivative thereof.
Claim 5
Dependent Claim
39 words
The method of claim 3 wherein said charge producing amphiphile is a negative charge producing material selected from a group consisting of dicetyl phosphate, cetyl sulphate, long chain fatty acids, retinoic acid, phosphatidic acid, phosphatidyl serine, and mixtures thereof.
Claim 6
Dependent Claim
34 words
The method of claim 3 wherein said charge producing amphiphile is a positive producing material selected from a group consisting of long chain amines, long chain pyridinium compounds, quaternary ammonium compounds, and mixtures thereof.
Claim 7
Dependent Claim
45 words
The method of claim 3 further comprising coupling a hydrophilic targeting molecule selected from a group consisting of monoclonal antibodies, lectins and peptide hormones to said surfactant, said hydrophilic targeting molecule being coupled directly to an OH residue of the polyoxyethylene portion of said surfactant.
Claim 8
Dependent Claim
48 words
The method of claim 3 further comprising coupling a hydrophilic targeting molecule selected from a group consisting of monoclonal antibodies, lectins and peptide hormones to said surfactant, said hydrophilic targeting molecule being coupled through a spacer molecule to an OH residue of the polyoxethylene portion of said surfactant.
Claim 9
Dependent Claim
42 words
The method of claim 3 further comprising coupling a hydrophilic targeting molecule selected from a group consisting of monoclonal antibodies, lectins and peptide hormones to said surfactant, said hydrophilic targeting molecule being coupled directly to an acyl chain interdigitating with said surfactant.
Claim 10
Dependent Claim
45 words
The method of claim 3 further comprising coupling a hydrophilic targeting molecule selected from a group consisting of monoclonal antibodies, lectins and peptide hormones to said surfactant, said hydrophilic targeting molecule being coupled through a spacer molecule to an acyl chain interdigitating with said surfactant.
Claim 11
Dependent Claim
15 words
The method of claim 3 wherein said polyoxyethylene fatty ether comprises polyoxyethylene (2) cetyl ether.
Claim 12
Dependent Claim
15 words
The method of claim 3 wherein said polyoxyethylene fatty ether comprises polyoxyethylene (4) lauryl ether.
Claim 13
Dependent Claim
13 words
The method of claim 3 wherein said charge producing molecule comprises retinoic acid.
Claim 14
Independent Claim
146 words
A method for encapsulating an amphiphilic material within a multilamellar lipid vesicle consisting essentially of the steps of: A. Providing a solventless non-aqueous lipophilic phase by blending a polyoxyethylene fatty ether surfactant with a sterol and a charge producing amphiphile while maintaining the temperature of said lipophilic phase above the melting point of said surfactant, and blending said amphiphilic material to be encapsulated into said lipophilic phase; B. Providing an aqueous phase formed of an aqueous solvent and any aqueous soluble materials to be encapsulated; and C. Combining said non-aqueous lipophilic phase with a substantial excess of said aqueous phase in a single step under shear conditions while maintaining the temperature of the mixture above the melting point of said surfactant; whereby said multilamellar lipid vesicles are formed and said amphiphilic material is encapsulated in less than two minutes without forming a separable hydrated lamellar phase.
Claim 15
Independent Claim
146 words
A method for encapsulating an amphiphilic material within a multilamellar lipid vesicle consisting essentially of the steps of: A. Providing a solventless non-aqueous lipophilic phase by blending a polyoxyethylene fatty ether surfactant with a sterol and a charge producing amphiphile while maintaining the temperature of said lipophilic phase above the melting point of said surfactant, and blending said amphiphilic material to be encapsulated into said lipophilic phase; B. Providing an aqueous phase formed of an aqueous solvent and any aqueous soluble materials to be encapsulated; and C. Combining said non-aqueous lipophilic phase with a substantial excess of said aqueous phase in a single step under shear conditions while maintaining the temperature of the mixture above the melting point of said surfactant; whereby said multilamellar lipid vesicles are formed and said amphiphilic material is encapsulated in less than two minutes without forming a separable hydrated lamellar phase.
Claim 16
Dependent Claim
44 words
The method of claim 13 wherein said surfactant comprises a polyoxyethylene fatty ether having the structure R.sub.1 --O--(CH.sub.2 --CH.sub.2 --O--).sub.m --H where R 1 is CH 3 --(CH 2 ) n , n ranges from 11 to 15, and m is 2 to 4.
Claim 17
Dependent Claim
14 words
The method of claim 14 wherein said sterol comprises cholesterol or a derivative thereof.
Claim 18
Dependent Claim
39 words
The method of claim 15 wherein said charge producing amphiphile is a negative charge producing material selected from a group consisting of dicetyl phosphate, cetyl sulphate, long chain fatty acids, retinoic acid, phosphatidic acid, phosphatidyl serine, and mixtures thereof.
Claim 19
Dependent Claim
35 words
The method of claim 15 wherein said charge producing amphiphile is a positive charge producing material selected from a group consisting of long chain amines, long chain pyridinium compounds, quaternary ammonium compounds, and mixtures thereof.
Claim 20
Dependent Claim
15 words
The method of claim 15 wherein said polyoxyethylene fatty ether comprises polyoxyethylene (2) cetyl ether.
Claim 21
Dependent Claim
15 words
The method of claim 15 wherein said polyoxyethylene fatty ether comprises polyoxyethylene (4) lauryl ether.
Claim 22
Independent Claim
138 words
A method of encapsulating hydrophilic material within a high aqueous volume multilamellar lipid vesicle consisting essentially of the steps of: A. Providing a solventless non-aqueous lipophilic phase by blending a polyoxyethylene fatty ether surfactant with a sterol and a charge producing amphiphile while maintaining the temperature of said lipophilic phase above the melting point of said surfactant; B. Providing an aqueous phase by blending said hydrophilic material to be encapsulated in an aqueous solvent; and C. Combining said non-aqueous lipophilic phase with a substantial excess of said aqueous phase in a single step under shear conditions while maintaining the temperature of the mixture above the melting point of said surfactant; whereby said high aqueous volume multilamellar lipid vesicles are formed and said hydrophilic material is encapsulated in less than two minutes without forming a separable hydrated lamellar phase.
Claim 23
Independent Claim
138 words
A method of encapsulating hydrophilic material within a high aqueous volume multilamellar lipid vesicle consisting essentially of the steps of: A. Providing a solventless non-aqueous lipophilic phase by blending a polyoxyethylene fatty ether surfactant with a sterol and a charge producing amphiphile while maintaining the temperature of said lipophilic phase above the melting point of said surfactant; B. Providing an aqueous phase by blending said hydrophilic material to be encapsulated in an aqueous solvent; and C. Combining said non-aqueous lipophilic phase with a substantial excess of said aqueous phase in a single step under shear conditions while maintaining the temperature of the mixture above the melting point of said surfactant; whereby said high aqueous volume multilamellar lipid vesicles are formed and said hydrophilic material is encapsulated in less than two minutes without forming a separable hydrated lamellar phase.
Claim 24
Dependent Claim
44 words
The method of claim 20 wherein said surfactant comprises a polyoxyethylene fatty ether having the structure R.sub.1 --O--(CH.sub.2 --CH.sub.2 --O--).sub.m --H where R 1 is CH 3 --(CH 2 ) n , n ranges from 11 to 15, and m is 2 to 4.
Claim 25
Dependent Claim
14 words
The method of claim 21 wherein said sterol comprises cholesterol or a derivative thereof.
Claim 26
Dependent Claim
39 words
The method of claim 22 wherein said charge producing amphiphile is a negative charge producing material selected from a group consisting of dicetyl phosphate, cetyl sulphate, long chain fatty acids, retinoic acid, phosphatidic acid, phosphatidyl serine, and mixtures thereof.
Claim 27
Dependent Claim
35 words
The method of claim 22 wherein said charge producing amphiphile is a positive charge producing material selected from a group consisting of long chain amines, long chain pyridinium compounds, quaternary ammonium compounds, and mixtures thereof.
Claim 28
Dependent Claim
15 words
The method of claim 22 wherein said polyoxyethylene fatty ether comprises polyoxyethylene (2) cetyl ether.
Claim 29
Dependent Claim
15 words
The method of claim 22 wherein said polyoxyethylene fatty ether comprises polyoxyethylene (4) lauryl ether.
Claim 30
Dependent Claim
12 words
The method of claim 20 wherein said hydrophilic material comprises a macromolecule.
Claim 31
Dependent Claim
11 words
The method of claim 27 wherein said hydrophilic material comprises hemoglobin.
Claim 32
Dependent Claim
13 words
The method of claim 20 wherein said hydrophilic material comprises a peptide hormone.
Claim 33
Dependent Claim
13 words
The method of claim 20 wherein said hydrophilic material comprises a growth factor.
Claim 34
Dependent Claim
12 words
The method of claim 20 wherein said hydrophilic material comprises a lymphokine.
Claim 35
Dependent Claim
11 words
The method of claim 20 wherein said hydrophilic material comprises interleukin.
Claim 36
Dependent Claim
11 words
The method of claim 20 wherein said hydrophilic material comprises interferon.
Claim 37
Dependent Claim
12 words
The method of claim 20 wherein said hydrophilic material comprises a virus.
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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) | 1992-08-07 | 1993-02-06 | 1993-08-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-08-07 | 1997-02-06 | 1997-08-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-08-07 | 2001-02-06 | 2001-08-08 | $7700.00 | Window Closed / Lapsed |