US5643553A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Stable microbubbles suspensions injectable into living organisms
Assignee: Bracco International BV
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Filing: 1995-09-26
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Granted: 1997-07-01
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Expires: 2015-09-26
Abstract
Abstract Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.
Inventors
- 👤 Michel Schneider
- 👤 Daniel Bichon
- 👤 Philippe Bussat
- 👤 Jerome Puginier
- 👤 Eva Hybl-Sutherland
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 12:57
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61K49/227
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
62 words
A composition suitable for injection into the bloodstream and body cavities of living beings, comprising a suspension of stabilized air or gas microbubbles in a physiologically acceptable aqueous carrier phase having one or more dissolved or dispersed surfactants, at least one of said surfactants being a film forming saturated phospholipid present in the composition at least partially in lamellar or laminar form.
Claim 2
Dependent Claim
62 words
A composition suitable for injection into the bloodstream and body cavities of living beings, comprising a suspension of stabilized air or gas microbubbles in a physiologically acceptable aqueous carrier phase having one or more dissolved or dispersed surfactants, at least one of said surfactants being a film forming saturated phospholipid present in the composition at least partially in lamellar or laminar form.
Claim 3
Dependent Claim
19 words
The composition of claim 1, wherein the lamellar surfactant is in the form of mono- or pluri-molecular membrane layers.
Claim 4
Dependent Claim
16 words
The composition of claim 1, containing about 10 8 -10 9 bubbles of 0.5-10 μm size/ml.
Claim 5
Dependent Claim
27 words
The composition of claim 1, wherein said saturated phospholipid is selected from the group consisting of lecithins, phosphatidic acid, phosphatidyl-choline, phosphatidyl-ethanolamine, phosphatidyl-serine, phosphatidyl-glycerol, phosphatidyl-inositol, cariolipin and sphyngomyelin.
Claim 6
Dependent Claim
36 words
The composition of claim 1, and further comprising a substance affecting the properties of liposomes selected from the group consisting of phosphatidyl-glycerol, dicetyl-phosphate, cholesterol, ergosterol, phytosterol, sitosterol, lanosterol, tocopterol, propyl gallate, ascorbyl palmitate and butylated hydroxy-toluene.
Claim 7
Dependent Claim
45 words
The composition of claim 1, and further comprising a dissolved viscosity enhancer or stabilizer selected from the group consisting of linear and cross-linked poly- and oligo-saccharides, sugars, hydrophilic polymers and iodinated compounds in a weight ratio to the surfactants of between about 1:5 to 100:1.
Claim 8
Dependent Claim
11 words
The composition of claim 6, wherein said iodinated compound is Iopamidol.
Claim 9
Dependent Claim
35 words
The composition of claim 1, wherein the surfactants comprise up to 50% by weight of non-laminar surfactants selected from the group consisting of fatty acids, ester and ethers of fatty acids and alcohols with polyols.
Claim 10
Dependent Claim
23 words
The composition of claim 8, wherein the non-laminar surfactant is selected from the group consisting of polyalkylene glycols, polyalkylenated sugars and polyalkylenated glyerol.
Claim 11
Dependent Claim
90 words
A method for the preparation of a composition as defined in claim 1, said method comprising the steps of: (a) selecting at least one film forming surfactant and converting it into lamellar form; (b) contacting the surfactant in lamellar form with air or an adsorbable or entrapable gas for a time sufficient for that air or gas to become bound by said surfactant; and (c) admixing the surfactant in lamellar form with an aqueous liquid carrier, to form a stable dispersion of air or gas microbubbles in said liquid carrier.
Claim 12
Dependent Claim
32 words
The method of claim 10, wherein step (c) is performed before step (b), step (b) being effected by introducing pressurized air or gas into the liquid carrier and thereafter releasing the pressure.
Claim 13
Dependent Claim
39 words
The method of claim 10, wherein step (c) is brought about by gentle mixing or the components with no shaking, whereby air or as bound to the lamellar surfactant in step (b) develops into a suspension of stable microbubbles.
Claim 14
Dependent Claim
31 words
The method of claim 10, wherein the aqueous liquid carrier contains dissolved therein stabilizer compounds selected from the group consisting of hydrosoluble proteins, polypeptides, sugars, poly- and oligo-saccharides and hydrophilic polymers.
Claim 15
Dependent Claim
54 words
The method of claim 10, wherein step (a) is effected by coating the surfactant onto particles of soluble or insoluble materials, wherein step (b) is effected by letting the coated particles stand for a while under air or gas and step (c) is effected by admixing the coated particles with an aqueous liquid carrier.
Claim 16
Dependent Claim
33 words
The method of claim 10, wherein step (a) is effected by sonicating or homogenizing under high pressure an aqueous solution of film forming lipids, leading, at least partly, to the formation of liposomes.
Claim 17
Dependent Claim
27 words
The method of claim 15, wherein step (b) is effected by freeze-drying the liposome containing solution and contacting the resulting freeze-dried product with air or a gas.
Claim 18
Dependent Claim
16 words
The method of claim 16, wherein in step (b) the liposome containing solution contains hydrophilic stabilizers.
Claim 19
Dependent Claim
41 words
The method of claim 15, wherein the aqueous solution of film forming lipids also contains viscosity enhancers or stabilizers selected from the group consisting of hydrophilic polymers and carbohydrates in weight ratio relative to the lipids of between 1:5 and 100:1.
Claim 20
Dependent Claim
16 words
The composition of claim 4, wherein in addition to phospholipids the composition comprises a non-ionic surfactant.
Claim 21
Dependent Claim
12 words
The composition of claim 19, wherein the non-ionic surfactant is polyoxyethylene-polyoxypropylene copolymer.
Claim 22
Dependent Claim
29 words
The composition of claim 20, wherein the non-ionic surfactant is present in an amount of up to 50% by weight of the total amount of surfactants in the composition.
Claim 23
Dependent Claim
29 words
The composition of claim 21, wherein the non-ionic surfactant is present in an amount of up to 30% by weight of the total amount of surfactants in the composition.
Claim 24
Dependent Claim
29 words
The composition of claim 22, wherein the non-ionic surfactant is present in an amount of up to 2.5% by weight of the total amount of surfactants in the composition.
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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) | 2000-06-30 | 2000-12-30 | 2001-07-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-06-30 | 2004-12-30 | 2005-07-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-06-30 | 2008-12-30 | 2009-07-01 | $7700.00 | Window Closed / Lapsed |