US4610868A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Lipid matrix carriers for use in drug delivery systems
Assignee: Elan Pharmaceuticals LLC
•
Filing: 1984-03-20
•
Granted: 1986-09-09
•
Expires: 2004-03-20
Abstract
Abstract Lipid matrix carriers are described which provide for the sustained release of bioactive agents in vivo or in vitro. The properties of the lipid matrix carriers of the present invention include high entrapment efficiencies; release of entrapped compounds in their active form; biodegradability and avoidance of vascular occlusion in vivo; and avoidance of sequestration of the bioactive agent in the liver and spleen.
Inventors
- 👤 Michael W. Fountain
- 👤 Steven J. Weiss
- 👤 John J. Kearns
- 👤 Alan L. Weiner
- 👤 Mircea C. Popescu
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 16:37
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 109
Claim 1
Independent Claim
84 words
Lipid matrix carriers comprising a hydrophobic compound, an amphipathic compound, and a bioactive agent combined in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm, the amphipathic compound being present in an amount ranging from about 2% to about 50%, by weight, of the water insoluble components so that the globular structures are stabilized and so that upon administration in vivo the bioactive agent is released at a slow and sustained rate from the globular structures.
Claim 2
Dependent Claim
84 words
Lipid matrix carriers comprising a hydrophobic compound, an amphipathic compound, and a bioactive agent combined in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm, the amphipathic compound being present in an amount ranging from about 2% to about 50%, by weight, of the water insoluble components so that the globular structures are stabilized and so that upon administration in vivo the bioactive agent is released at a slow and sustained rate from the globular structures.
Claim 3
Dependent Claim
35 words
The lipid matrix carriers according to claim 1 in which the amphipathic compound is present in a range from about 2% to about 35%, by weight, of the water insoluble components of the globular structures.
Claim 4
Dependent Claim
35 words
The lipid matrix carriers according to claim 1 in which the amphipathic compound is present in a range from about 2% to about 25%, by weight, of the water insoluble components of the globular structures.
Claim 5
Dependent Claim
21 words
The lipid matrix carriers according to claim 1 in which the hydrophobic compound comprises a mixture of monoglycerides, diglycerides and triglycerides.
Claim 6
Dependent Claim
21 words
The lipid matrix carriers according to claim 1 in which the hydrophobic compound comprises a triglyceride or a mixture of triglycerides.
Claim 7
Dependent Claim
18 words
The lipid matrix carriers according to claim 4 in which the mixture of triglycerides comprises oils of fats.
Claim 8
Dependent Claim
17 words
The lipid matrix carriers according to claim 6 in which the mixture of triglycerides comprises vegetable oils.
Claim 9
Dependent Claim
30 words
The lipid matrix carriers according to claim 7 in which the vegetable oil comprises corn oil, palm kernal oil, coconut oil, soybean oil, sunflower oil, safflower oil, or cocoa butter.
Claim 10
Dependent Claim
16 words
The lipid matrix carriers according to claim 1 in which the hydrophobic compound comprises a sterol.
Claim 11
Dependent Claim
21 words
The lipid matrix carriers according to claim 11 in which the sterol comprises a cholesterol, a cholesterol ester, or derivatives thereof.
Claim 12
Dependent Claim
20 words
The lipid matrix carriers according to claim 1 in which the hydrophobic compound comprises a tocopherol or a derivative thereof.
Claim 13
Dependent Claim
17 words
The lipid matrix carriers according to claim 1 in which the hydrophobic compound comprises a petroleum jelly.
Claim 14
Dependent Claim
16 words
The lipid matrix carriers according to claim 1 in which the amphipathic compound comprises a surfactant.
Claim 15
Dependent Claim
17 words
The lipid matrix carriers according to claim 1 in which the amphipathic compound comprises an amphipathic lipid.
Claim 16
Dependent Claim
29 words
The lipid matrix carriers according to claim 14 in which the amphipathic lipid contains a hydrophilic phosphate group, carboxylic group, sulphato group, sulfhydryl group, amino group or nitro group.
Claim 17
Dependent Claim
28 words
The lipid matrix carriers according to claim 14 in which the amphipathic lipid contains a hydrophobic long chain aliphatic hydrocarbon group, aromatic group, cycloaliphatic group, or heterocyclic group.
Claim 18
Dependent Claim
16 words
The lipid matrix carriers according to claim 14 in which the amphipathic lipid is a phosphoglyceride.
Claim 19
Dependent Claim
28 words
The lipid matrix carriers according to claim 17 in which the phosphoglyceride is phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine, dioleoylphosphatidylcholine, or dilinoleoylphosphatidylcholine.
Claim 20
Dependent Claim
21 words
The lipid matrix carriers according to claim 14 in which the amphipathic lipid is a sphingolipid, a glycosphingolipid, or derivatives thereof.
Claim 21
Dependent Claim
12 words
The lipid matrix carriers according to claim 14 further comprising a surfactant.
Claim 22
Dependent Claim
16 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is water soluble.
Claim 23
Dependent Claim
16 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is lipid soluble.
Claim 24
Dependent Claim
26 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of: antibacterial, antifungal, antiviral, and antiparasitic compounds.
Claim 25
Dependent Claim
17 words
The lipid matrix carriers according to claim 23 in which the entrapped bioactive agent comprises an aminoglycoside.
Claim 26
Dependent Claim
18 words
The lipid matrix carriers according to claim 24 in which the aminoglycoside is gentamicin or a derivative thereof.
Claim 27
Dependent Claim
18 words
The lipid matrix carriers according to claim 24 in which the aminoglycoside is streptomycin or a derivative thereof.
Claim 28
Dependent Claim
17 words
The lipid matrix carriers according to claim 23 in which the entrapped bioactive agent comprises a tetracycline.
Claim 29
Dependent Claim
18 words
The lipid matrix carriers according to claim 27 in which the tetracycline is oxytetracycline or a derivative thereof.
Claim 30
Dependent Claim
18 words
The lipid matrix carriers according to claim 23 in which the entrapped bioactive agent comprises a macrolide antibiotic.
Claim 31
Dependent Claim
19 words
The lipid matrix carriers according to claim 3 in which the macrolide antibiotic is tylosin or a derivative thereof.
Claim 32
Dependent Claim
19 words
The lipid matrix carriers according to claim 29 in which the macrolide antibiotic is erythromycin or a derivative thereof.
Claim 33
Dependent Claim
19 words
The lipid matrix carriers according to claim 1 in which the bioactive agent comprises a cell receptor binding compound.
Claim 34
Dependent Claim
28 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of: hormones, neurotransmitters, tumoricidal compounds, growth factors, and toxins.
Claim 35
Dependent Claim
25 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of: peptides, proteins, glycoproteins, and lipoproteins.
Claim 36
Dependent Claim
17 words
The lipid matrix carriers according to claim 34 in which the entrapped bioactive agent is an immunoglobulin.
Claim 37
Dependent Claim
17 words
The lipid matrix carriers according to claim 1 in which the bioactive agent comprises an immunomodulating compound.
Claim 38
Dependent Claim
23 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of catalysts and enzymes.
Claim 39
Dependent Claim
26 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting: dyes, radiolabels, radio-opaque compounds and fluorescent compounds.
Claim 40
Dependent Claim
27 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of: anti-inflammatory, antiglaucomic, mydriatic, analgesic and anaesthetic compounds.
Claim 41
Dependent Claim
16 words
The lipid matrix carriers according to claim 39 in which the entrapped bioactive agent is indomethacin.
Claim 42
Dependent Claim
16 words
The lipid matrix carriers according to claim 1 in which the bioactive agent comprises a narcotic.
Claim 43
Dependent Claim
14 words
The lipid matrix carriers according to claim 41 in which the narcotic is diazepam.
Claim 44
Dependent Claim
24 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of: nucleic acids and polynucleotides.
Claim 45
Dependent Claim
24 words
The lipid matrix carriers according to claim 1 in which the bioactive agent is selected from the group consisting of: monosaccharides, disaccharides and polysaccharides.
Claim 46
Dependent Claim
16 words
The lipid matrix carriers according to claim 1 in which the bioactive agent comprises a vitamin.
Claim 47
Dependent Claim
158 words
A process for preparing lipid matrix carriers, comprising: (a) emulsifying a mixture comprising an amphipathic compound combined with at least an equal amount by weight of a hydrophobic compound and a volume of aqueous phase ranging from about 0.7% to about 10.25% of the volume of the combined amphipathic compound and hydrophobic compound so that a water-in-oil emulsion is formed; and (b) injecting the water-in-oil emulsion into a volume of organic solvent in excess of the volume of the water-in-oil emulsion, the organic solvent being capable of both solubilizing the amphipathic compound and removing water, so that lipid matrix carriers in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm are formed, the amphipathic compound being present in an amount sufficient to stabilize the globular structures and the globular structures being further characterized as capable of releasing their contents in vivo or in vitro at a slow and sustained rate.
Claim 48
Dependent Claim
158 words
A process for preparing lipid matrix carriers, comprising: (a) emulsifying a mixture comprising an amphipathic compound combined with at least an equal amount by weight of a hydrophobic compound and a volume of aqueous phase ranging from about 0.7% to about 10.25% of the volume of the combined amphipathic compound and hydrophobic compound so that a water-in-oil emulsion is formed; and (b) injecting the water-in-oil emulsion into a volume of organic solvent in excess of the volume of the water-in-oil emulsion, the organic solvent being capable of both solubilizing the amphipathic compound and removing water, so that lipid matrix carriers in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm are formed, the amphipathic compound being present in an amount sufficient to stabilize the globular structures and the globular structures being further characterized as capable of releasing their contents in vivo or in vitro at a slow and sustained rate.
Claim 49
Dependent Claim
12 words
The process according to claim 46 further comprising removing the organic solvent.
Claim 50
Dependent Claim
121 words
A process for preparing lipid matrix carriers, comprising: (a) combining an amphipathic compound with at least an equal amount by weight of a hydrophobic compound to form a mixture; and (b) injecting the mixture into a volume of organic solvent in excess of the volume of the mixture, the organic solvent being capable of solubilizing the amphipathic compound, so that lipid matrix carriers in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm are formed, the amphipathic compound being present in an amount sufficient to stabilize the globular structures and the globular structures being further characterized as capable of releasing their contents in vivo or in vitro at a slow and sustained rate.
Claim 51
Dependent Claim
121 words
A process for preparing lipid matrix carriers, comprising: (a) combining an amphipathic compound with at least an equal amount by weight of a hydrophobic compound to form a mixture; and (b) injecting the mixture into a volume of organic solvent in excess of the volume of the mixture, the organic solvent being capable of solubilizing the amphipathic compound, so that lipid matrix carriers in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm are formed, the amphipathic compound being present in an amount sufficient to stabilize the globular structures and the globular structures being further characterized as capable of releasing their contents in vivo or in vitro at a slow and sustained rate.
Claim 52
Dependent Claim
12 words
The process according to claim 48 further comprising removing the organic solvent.
Claim 53
Dependent Claim
112 words
A process for the preparation of lipid matrix carriers, comprising: (a) combining an amphipathic compound with at least an equal amount by weight of a hydrophobic compound in an organic solvent to form a solution; and (b) adding the solution to an excess volume of aqueous phase with agitation so that lipid matrix carriers in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm are formed, the amphipathic compound being present in an amount sufficient to stabilize the globular structures, and the globular structures being further characterized as capable of releasing their contents in vivo or in vitro at a slow and sustained rate.
Claim 54
Dependent Claim
112 words
A process for the preparation of lipid matrix carriers, comprising: (a) combining an amphipathic compound with at least an equal amount by weight of a hydrophobic compound in an organic solvent to form a solution; and (b) adding the solution to an excess volume of aqueous phase with agitation so that lipid matrix carriers in the form of globular structures having a diameter ranging from about 500 nm to about 100,000 nm are formed, the amphipathic compound being present in an amount sufficient to stabilize the globular structures, and the globular structures being further characterized as capable of releasing their contents in vivo or in vitro at a slow and sustained rate.
Claim 55
Dependent Claim
12 words
The process according to claim 50 further comprising removing the organic solvent.
Claim 56
Dependent Claim
22 words
The process according to claim 46, 48 or 50 in which the hydrophobic compound comprises a mixture of monoglycerides, diglycerides, and triglycerides.
Claim 57
Dependent Claim
22 words
The process according to claim 46, 48 or 50 in which the hydrophobic compound comprises a triglyceride or a mixture of triglycerides.
Claim 58
Dependent Claim
15 words
The process according to claim 53 in which the mixture of triglycerides comprises corn oil.
Claim 59
Dependent Claim
18 words
The process according to claim 46, 48 or 50 in which the hydrophobic compound is a petroleum jelly.
Claim 60
Dependent Claim
17 words
The process according to claim 46, 48 or 50 in which the amphipathic compound comprises a surfactant.
Claim 61
Dependent Claim
18 words
The process according to claim 46, 48 or 50 in which the amphipathic compound comprises an amphipathic lipid.
Claim 62
Dependent Claim
17 words
The process according to claim 46, 48 or 50 in which the amphipathic lipid comprises a phospholipid.
Claim 63
Dependent Claim
12 words
The process according to claim 58 in which the phospholipid comprises phosphatidylcholine.
Claim 64
Dependent Claim
21 words
The process according to claim 46, 48 or 50 in which the amphipathic lipid is a sphingolipid or a derivative thereof.
Claim 65
Dependent Claim
37 words
The process according to claim 54 in which the amphipathic compound comprises 1 mg to 200 mg phosphatidylcholine which is combined with 6.2 g corn oil and in which the organic solvent is maintained at room temperature.
Claim 66
Dependent Claim
40 words
The process according to claim 54 in which the amphipathic compound comprises 1 mg to 200 mg phosphatidylcholine which is combined with 6.2 g corn oil and in which the organic solvent is maintained between 4° C. and 10° C.
Claim 67
Dependent Claim
37 words
The process according to claim 54 in which the amphipathic compound comprises 1 mg to 200 mg sphingomyelin which is combined with 6.2 g corn oil and in which the organic solvent is maintained at room temperature.
Claim 68
Dependent Claim
40 words
The process according to claim 54 in which the amphipathic compound comprises 1 mg to 200 mg sphingomyelin which is combined with 6.2 g corn oil and in which the organic solvent is maintained between 4° C. and 10° C.
Claim 69
Dependent Claim
40 words
The process according to claim 55 in which the amphipathic compound comprises 1 mg to 200 mg phosphatidylcholine which is combined with 6.2 g petroleum jelly and in which the organic solvent is maintained between 4° C. and 10° C.
Claim 70
Dependent Claim
40 words
The process according to claim 55 in which the amphipathic compound comprises 1 mg to 200 mg sphingomyelin which is combined with 6.2 g petroleum jelly and in which the organic solvent is maintained between 4° C. and 10° C.
Claim 71
Dependent Claim
20 words
The process according to claim 46, 48 or 50 further comprising the addition of a surfactant to the amphipathic compound.
Claim 72
Dependent Claim
14 words
The process according to claim 67 in which the surfactant comprises polyoxyethylene sorbitan monooleate.
Claim 73
Dependent Claim
19 words
The process according to claim 46 in which a water soluble bioactive agent is added to the aqueous phase.
Claim 74
Dependent Claim
16 words
The process according to claim 48 in which a bioactive agent is added to the mixture.
Claim 75
Dependent Claim
19 words
The process according to claim 50 in which a lipid soluble bioactive agent is added to the organic solvent.
Claim 76
Dependent Claim
27 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: antibacterial, antifungal, antiviral, and antiparasitic compounds.
Claim 77
Dependent Claim
14 words
The process according to claim 72 in which the bioactive agent comprises an aminoglycoside.
Claim 78
Dependent Claim
16 words
The process according to claim 73 in which the aminoglycoside comprises gentamicin or a derivative thereof.
Claim 79
Dependent Claim
16 words
The process according to claim 73 in which the aminoglycoside comprises streptomycin or a derivative thereof.
Claim 80
Dependent Claim
14 words
The process according to claim 72 in which the bioactive agent comprises a tetracylcine.
Claim 81
Dependent Claim
16 words
The process according to claim 76 in which the tetracycline comprises oxytetracycline or a derivative thereof.
Claim 82
Dependent Claim
15 words
The process according to claim 72 in which the bioactive agent comprises a macrolide antibiotic.
Claim 83
Dependent Claim
17 words
The process according to claim 78 in which the macrolide antibiotic comprises tylosin or a derivative thereof.
Claim 84
Dependent Claim
17 words
The process according to claim 78 in which the macrolide antibiotic comprises erythromycin or a derivative thereof.
Claim 85
Dependent Claim
20 words
The process according to claim 69, 70 or 71 in which the bioactive agent is a cell receptor binding compound.
Claim 86
Dependent Claim
29 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: hormones, neurotransmitters, tumoricidal compounds, growth factors, and toxins.
Claim 87
Dependent Claim
26 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: peptides, proteins, glycoproteins, and lipoproteins.
Claim 88
Dependent Claim
14 words
The process according to claim 83 in which the bioactive agent is an immunoglobulin.
Claim 89
Dependent Claim
18 words
The process according to claim 69, 70 or 71 in which the bioactive agent is an immunomodulating compound.
Claim 90
Dependent Claim
24 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of catalysts and enzymes.
Claim 91
Dependent Claim
28 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: dyes, radiolabels, radio-opaque compounds, and fluorescent compounds.
Claim 92
Dependent Claim
28 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: anti-inflammatory, antiglaucomic, mydriatic, analgesic and anaesthetic compounds.
Claim 93
Dependent Claim
13 words
The process according to claim 88 in which the bioactive agent is indomethacin.
Claim 94
Dependent Claim
17 words
The process according to claim 69, 70 or 71 in which the bioactive agent comprises a narcotic.
Claim 95
Dependent Claim
12 words
The process according to claim 90 in which the narcotic comprises diazepam.
Claim 96
Dependent Claim
25 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: nucleic acids and polynucleotides.
Claim 97
Dependent Claim
25 words
The process according to claim 69, 70 or 71 in which the bioactive agent is selected from the group consisting of: monosaccharides, disaccharides, and polysaccharides.
Claim 98
Dependent Claim
17 words
The process according to claim 69, 70 or 71 in which the bioactive agent comprises a vitamin.
Claim 99
Dependent Claim
16 words
The process according to claim 46, 48 or 50 in which the organic solvent is acetone.
Claim 100
Dependent Claim
24 words
The process according to claim 95 in which the organic comprises 20 ml of acetone and the volume of the emulsion is 9 ml.
Claim 101
Dependent Claim
16 words
The process according to claim 46, 48 or 50 in which the organic solvent is chloroform.
Claim 102
Dependent Claim
16 words
The process according to claim 46, 48 or 50 in which the organic solvent is ethanol.
Claim 103
Dependent Claim
17 words
The process according to claim 46, 48 or 50 in which the organic solvent is diethyl ether.
Claim 104
Dependent Claim
17 words
The process according to claim 46, 48 or 50 in which the organic solvent is petroleum ether.
Claim 105
Dependent Claim
22 words
The process according to claim 46, 48 or 50 further comprising the step of separating the lipid matrix carriers from unincorporated components.
Claim 106
Dependent Claim
24 words
A method for the delivery in vivo of a bioactive compound comprising administering intramuscularly to a host the lipid matrix carriers of claim 1.
Claim 107
Dependent Claim
24 words
A method for the delivery in vivo of a bioactive compound comprising administering subcutaneously to a host the lipid matrix carriers of claim 1.
Claim 108
Dependent Claim
24 words
A method for the delivery in vivo of a bioactive compound comprising administering topically to a host the lipid matrix carriers of claim 1.
Claim 109
Dependent Claim
20 words
A method according to claim 104 in which the topical administration is oral, otic, ophthalmic, nasal, urethral, rectal or vaginal.
References Cited (Backward Citations)
US3159545A
Cited
US3159600A
Cited
US4010038A
Cited
US3993754A
Cited
US4145410A
Cited
US4224179A
Cited
US4356167A
Cited
US4235871A
Cited
US4298594A
Cited
US4377567A
Cited
US4310506A
Cited
US4404183A
Cited
US4317743A
Cited
US4349529A
Cited
US4434153A
Cited
US4460560A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-09-08 | 1990-03-10 | 1990-09-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-09-08 | 1994-03-10 | 1994-09-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-09-08 | 1998-03-10 | 1998-09-09 | $7700.00 | Window Closed / Lapsed |