US4973465A
Expired / Lapsed
US
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Microcrystals comprising an active substance having an affinity for phospholipids, and at least one phospholipid, process of preparation
Assignee: Leadiant Biosciences Ltd
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Filing: 1989-06-08
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Granted: 1990-11-27
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Expires: 2009-06-08
Abstract
Abstract The present invention relates to microcrystals of a substance, which substance is insoluble in water and has an affinity for phospholipids, as well as a process for its preparation. According to the invention, one or more organic solvents are evaporated from a solution of phospholipids and substance, and the film obtained thereby, after evaporation of the one or more solvents, is suspended in an aqueous solution by vigorous stirring. The invention also relates to pharmaceutical compositions containing as active principle these microcrystals, particularly liquid pharmaceutical compositions packaged in injectable form or in sprayable form.
Inventors
- 👤 Roger Baurain
- 👤 Andre B. L. Trouet
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 21:19
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/51; A61K9/5107; A61K9/5123; A61K9/10; A61K9/127; A61K9/1277; A61K9/14; A61K9/16; A61K9/1605; A61K9/1617; A61P; A61P11/00; A61P11/08; A61P7/00; A61P7/02
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
121 words
Process for the preparation of lipidic microparticles of an active substance and at least one phospholipid, the microparticles having a crystalline appearance and being stable in suspension in aqueous solution, said process comprising the steps of: providing a solution of a phospholipid and an active substance in one or more organic solvents, said active substance being substantially insoluble in water and having an affinity for phospholipids; evaporating the one or more organic solvents from said solution of phospholipid and said active substance to produce a film; and then suspending the film in an aqueous solution by vigorous stirring to produce lipidic microparticles of crystalline appearnace, wherein the molar ratio between the phospholipid and the active substance is between 0.8 and 1.2.
Claim 2
Dependent Claim
121 words
Process for the preparation of lipidic microparticles of an active substance and at least one phospholipid, the microparticles having a crystalline appearance and being stable in suspension in aqueous solution, said process comprising the steps of: providing a solution of a phospholipid and an active substance in one or more organic solvents, said active substance being substantially insoluble in water and having an affinity for phospholipids; evaporating the one or more organic solvents from said solution of phospholipid and said active substance to produce a film; and then suspending the film in an aqueous solution by vigorous stirring to produce lipidic microparticles of crystalline appearnace, wherein the molar ratio between the phospholipid and the active substance is between 0.8 and 1.2.
Claim 3
Dependent Claim
10 words
Process according to claim 1 wherein the phospholipid is phosphatidylcholine.
Claim 4
Dependent Claim
16 words
Process according to claim 1, wherein the organic solvent is methanol, chloroform or a mixture thereof.
Claim 5
Dependent Claim
75 words
Process according to claim 1, wherein the step of providing the solution of the phospholipid and the active substance in the organic solvent comprises the substeps of: providing a phospholid solution comprising a phospholipid and one or more solvents; evaporating the one or more solvents from the phospholipid solution to produce a lipid film; and then dissolving the lipid film by adding thereto a solution of the active substance in one or more organic solvents.
Claim 6
Dependent Claim
16 words
Process according to claim 1, wherein the vigorous stirring is obtained by treatment with ultrasonic vibrations.
Claim 7
Dependent Claim
24 words
Process according to claim 4, wherein the one or more solvents of the phospholipid solution is chloroform or a mixture of chloroform and methanol.
Claim 8
Dependent Claim
26 words
Process according to claim 4, wherein the one or more organic solvents in the solution of said active substance is a mixture of chloroform and methanol.
Claim 9
Dependent Claim
26 words
Process according to claim 1, wherein said active substance is selected form the group consisting of substances antagonistic to the acether of the "platelet activation factor".
Claim 10
Dependent Claim
19 words
Process according to claim 8, wherein the active substance is selected from the group consisting of lignans and neolignans.
Claim 11
Dependent Claim
21 words
Process according to claim 8, wherein the active substance is selected from the group consisting of kadsurenone and synthetic dinorlignan L-652,731.
Claim 12
Dependent Claim
17 words
Process according to claim 8, wherein the active substance is selected from the group consisting of ginkgolides.
Claim 13
Dependent Claim
26 words
Process according to claim 1, wherein said active substance is selected from the group consisting of amphotericin B and its aminoacyl derivatives, having an antifungal activity.
Claim 14
Dependent Claim
20 words
Process according to claim 1, wherein the solution of the phospholipid and the active substance is supplemented with a sterol.
Claim 15
Dependent Claim
20 words
Process according to claim 13, wherein the molar ratio between the phospholipid and the sterol is between 1 and 2.
Claim 16
Dependent Claim
31 words
Process according to claim 10 or 11, wherein the film obtained by evaporation of the organic solvent is suspended in an aqueous solution buffered to a pH between 5 and 8.
Claim 17
Dependent Claim
28 words
Process according to claim 10 or 11, wherein the film obtained by evaporation of the organic solvent is suspended in an aqueous solution of acetate or phosphate buffer.
Claim 18
Dependent Claim
19 words
Process according to claim 12, wherein the aqueous solution is a solution of Nacl or of 0.1 M saccharide.
Claim 19
Dependent Claim
24 words
Process according to claim 1, further comprising the step of purifying the microparticles by centrifugation and washing with distilled water or an aqueous solution.
Claim 20
Dependent Claim
41 words
Lipidic microparticles of crystalline appearance comprising an active substance and at least one phospholipid, said active substance being insoluble in water and having an affinity for phospholipids, wherein the molar ratio of phospholipid to active substance is between 0.8 and 1.2.
Claim 21
Dependent Claim
41 words
Lipidic microparticles of crystalline appearance comprising an active substance and at least one phospholipid, said active substance being insoluble in water and having an affinity for phospholipids, wherein the molar ratio of phospholipid to active substance is between 0.8 and 1.2.
Claim 22
Dependent Claim
10 words
Microparticles according to claim 19, wherein a phospholipid is phosphatidylcholine.
Claim 23
Dependent Claim
13 words
Microparticles according to claim 19, wherein the active substance is an anti-PAF-acether agent.
Claim 24
Dependent Claim
17 words
Microparticles according to claim 19 wherein the active substance is selected from the group consisting of ginkgolides.
Claim 25
Dependent Claim
21 words
Microparticles according to claim 19, wherein the active substance is selected from the group consisting of kadsurenone and synthetic dinorlignane L652,731.
Claim 26
Dependent Claim
23 words
Microparticles according to claim 19, wherein the active substance is selected from the group consisting of amphotericin B and its aminoacyl anti-fungal derivatives.
Claim 27
Dependent Claim
9 words
Microparticles according to claim 19, further comprising a sterol.
Claim 28
Dependent Claim
21 words
Microparticles according to claim 25 wherein the molar ratio of phospholipid to active substance and sterol is between 0.8 and 1.4.
Claim 29
Dependent Claim
20 words
Microparticles according to claim 19, consisting essentially of amphotericin B, cholesterol and phosphatidylcholine in a molar ratio of 1:2:4 respectively.
Claim 30
Dependent Claim
13 words
Microparticles according to claim 19, wherein the microparticles are in freeze dried form.
Claim 31
Dependent Claim
13 words
Pharmaceutical composition comprising microparticles according to claim 19 as the active ingredient thereof.
Claim 32
Dependent Claim
17 words
Pharmaceutical composition according to claim 29, which is a liquid administrable by injection or as a spray.
Claim 33
Dependent Claim
11 words
Pharmaceutical composition according to claim 29, which is in freeze-dried form.
Claim 34
Dependent Claim
11 words
Process according to claim 1, wherein said active substance is nystatin.
Claim 35
Dependent Claim
11 words
Microparticles according to claim 19, wherein the active substance is nystatin.
Claim 36
Dependent Claim
11 words
Microparticles according to claim 33, consisting essentially of nystatin and phosphatidylcholine.
References Cited (Backward Citations)
US2664380A
Cited
USRE32393E
Cited
USRE32393F1
Cited
US4396630A
Cited
US4687762A
Cited
US4647586A
Cited
US4727077A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1993-11-26 | 1994-05-28 | 1994-11-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-11-26 | 1998-05-28 | 1998-11-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-11-26 | 2002-05-28 | 2002-11-27 | $7700.00 | Window Closed / Lapsed |