US6042809A
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Administrable compositions and methods for magnetic resonance imaging
Assignee: Bracco Suisse SA
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Filing: 1998-08-12
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Granted: 2000-03-28
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Expires: 2018-08-12
Abstract
Abstract The invention relates to the application of hyperpolarized gases to magnetic resonance imaging (MRI) of living subjects. The invention also concerns administrable compositions, formulations, methods of making the compositions and formulations and contrast agents involving hyperpolarized gases, as well as their use in MRI.
Inventors
- 👤 Herve Tournier
- 👤 Michel Schneider
- 👤 Feng Yan
- 👤 Jean Brochot
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 00:12
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; A61K49/18; A61K49/1806; A61K49/22; A61K49/222; A61K49/223
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
39 words
Gas filled microvesicles bounded by a gas/liquid interface in a liquid carrier comprising one or more amphiphiles stabilizing microvesicles or a polymeric membrane, characterized in that the gas comprises a mixture of a hyperpolarized gas and a halogenated gas.
Claim 2
Dependent Claim
39 words
Gas filled microvesicles bounded by a gas/liquid interface in a liquid carrier comprising one or more amphiphiles stabilizing microvesicles or a polymeric membrane, characterized in that the gas comprises a mixture of a hyperpolarized gas and a halogenated gas.
Claim 3
Dependent Claim
25 words
The microvesicles of claim 1, wherein the hyperpolarized gas is selected from 3 helium, argon, 129 xenon, 131 xenon or krypton, preferably helium or xenon.
Claim 4
Dependent Claim
13 words
The microvesicles of claim 1, wherein said halogenated gas is fluorinated, preferably perfluorinated.
Claim 5
Dependent Claim
69 words
The microvesicles of claim 3, wherein the fluorinated gas is selected from at least one of SF 6 , CF 4 , C 2 F 6 , C 3 F 6 , C 3 F 8 , C 4 F 6 , C 4 F 8 , C 4 F 10 , C 5 F 10 , C 5 F 12 , C 6 F 14 and mixtures thereof.
Claim 6
Dependent Claim
12 words
The microvesicles of claim 1, having an average size of 0.1-10 μm.
Claim 7
Dependent Claim
25 words
The microvesicles of claim 1, wherein said amphiphile is selected from sugar derivatives, natural or synthetic amphiphilic polymers, polyoyxethylene-polyoxypropylene block copolymers, phospholipids and the like.
Claim 8
Dependent Claim
24 words
The microvesicles of claim 6, wherein said phospholipids comprises hydrophilic moieties selected from the group consisting of choline, ethanolamine, serine, glycerol, pentoses and hexoses.
Claim 9
Dependent Claim
13 words
The microvesicles of claim 6, wherein the phospholipid comprises film forming saturated phospholipids.
Claim 10
Dependent Claim
21 words
The microvesicles of claim 6, wherein the phospholipids are selected from phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, cardiolipin and sphingomyelin.
Claim 11
Dependent Claim
29 words
The microvesicles of claim 9, wherein the phospholipids further contain substances selected from dicetylphosphate, cholesterol, ergosterol, phytosterol, sitosterol, lanosterol, tocopherol, propyl gallate, ascorbyl palmitate, butylated hydroxytoluene and fatty acids.
Claim 12
Dependent Claim
13 words
The microvesicles of claim 10, wherein the phospholipids comprise lecithins or derivative thereof.
Claim 13
Dependent Claim
21 words
The microvesicles of claim 1, comprising a fluorinated high molecular weight hydrocarbon gas, and stabilized by monolayers of said phospholipid material.
Claim 14
Dependent Claim
23 words
The microvesicles of claim 1 wherein said polymer is selected from natural or synthetic proteins, hydrocarbons, fluorinated hydrocarbons, polymerisable phospholipids and polyamino acids.
Claim 15
Dependent Claim
35 words
The microvesicles of claim 1 wherein the polymer is a biodegradable polymer selected from polysaccharides, polyamino-acids, polylactides and polyglycolides and their copolymers, copolymers of lactides and lactones, polypeptides, poly-(ortho)esters, polydioxanone, poly-β-aminoketones, polyphosphazenes, polyanhydrides and polyalkyl(cyano)acrylates.
Claim 16
Dependent Claim
23 words
The microvesicles of claims 1 wherein the membrane polymer is selected from polyglutamic or polyaspartic acid derivatives and their copolymers with other amino-acids.
Claim 17
Dependent Claim
10 words
An aqueous dispersion comprising the gas microvesicles of claim 6.
Claim 18
Dependent Claim
43 words
An aqueous dispersion comprising the gas microvesicles of claim 6 containing, dissolved, viscosity enhancers or stabilizers selected from linear and cross-linked poly- and oligo-saccharides, sugars, hydrophilic polymers and iodinated compounds in a weight ratio to the surfactants comprised between about 1:5 to 100:1.
Claim 19
Dependent Claim
34 words
The aqueous dispersion of claim 17, further comprising up to 50% by weight of non-laminar surfactants selected from fatty acids, esters of fatty acids and alcohols or polyols, and ethers of alcohols and/or polyols.
Claim 20
Dependent Claim
20 words
The aqueous dispersion of claim 18, wherein the polyols are polyalkylene glycols, polyalkylenated sugars and other carbohydrates, and polyalkylenated glycerol.
Claim 21
Dependent Claim
28 words
An aqueous dispersion of the gas microvesicles of claim 1, containing 10 7 -10 8 , or 10 8 -10 9 , or 10 10 -10 11 microbubbles/ml.
Claim 22
Dependent Claim
37 words
A process for preparation of an MRI contrast agent which comprises generating gas microvesicles containing a biocompatible hyperpolarized gas and a halogenated gas in a carrier liquid comprising one or more surfactants capable of generating gas-containing microvesicles.
Claim 23
Dependent Claim
37 words
A process for preparation of an MRI contrast agent which comprises generating gas microvesicles containing a biocompatible hyperpolarized gas and a halogenated gas in a carrier liquid comprising one or more surfactants capable of generating gas-containing microvesicles.
Claim 24
Dependent Claim
23 words
The process of claim 21, which comprises shaking or sonicating a fluorinated and a hyperpolarized gas(es) in an amphiphile-containing liquid comprising a phospholipid.
Claim 25
Dependent Claim
14 words
The process of claim 21, wherein the contrast agent is isolated by freeze drying.
Claim 26
Dependent Claim
11 words
An MRI contrast agent prepared by the process of claim 21.
Claim 27
Dependent Claim
24 words
A diagnostic MRI contrast agent prepared according to claim 22 for use in MRI imaging of organs and tissue of human and animal patients.
Claim 28
Dependent Claim
15 words
A bifunctional MRI and ultrasonic contrast agent prepared according to the process of claim 22.
Claim 29
Dependent Claim
40 words
A kit comprising a dry formulation comprising a surfactant material capable of formation of gas-containing microvesicles of claim 1 under atmosphere of a mixture of a hyperpolarized gas and at least one biocompatible halogenated gas, and an aqueous carrier liquid.
Claim 30
Dependent Claim
41 words
A kit comprising a dry formulation comprising a surfactant material capable of formation of gas-containing microvesicles of claim 1, stored under partial pressure of the stabilising gas, a second component a hyperpolarized gas and a third component physiologically acceptable carrier liquid.
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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) | 2003-03-28 | 2003-09-27 | 2004-03-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2007-03-28 | 2007-09-27 | 2008-03-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2011-03-28 | 2011-09-27 | 2012-03-28 | $7700.00 | Window Closed / Lapsed |