Patent US5558855A successfully refreshed from Google Patents.
US5558855A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Phase shift colloids as ultrasound contrast agents
Assignee: GE Healthcare Ltd
•
Filing: 1993-01-25
•
Granted: 1996-09-24
•
Expires: 2013-01-25
Abstract
Abstract Disclosed herein are agents for enhancing the contrast in a diagnostic ultrasound procedure. These agents comprise colloidal dispersions of the liquid-in-liquid type, i.e., emulsions or microemulsions, in which the dispersed liquid phase has a boiling point at or below the body temperature of the organism to be studied and thus undergoes a phase change from a dispersed liquid to a highly echogenic dispersed gaseous foam or kugelschaum following administration to an organism. The liquid state of the dispersed phase allows one to manufacture extremely stable, pharmaceutically acceptable emulsions with particle sizes typically below 1000 nm. The gaseous state at body temperature yields highly echogenic microbubbles, typically below 10,000 nm in diameter, which are effective as ultrasound contrast agents. Intravenous, intraarterial, oral, intraperitoneal, and intrauterine dosage forms, methods of administration, and imaging techniques are described.
Inventors
- 👤 Steven C. Quay
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 17:46
CPC Classifications
A; A61; A61K; A61K47/00; A61K47/30; A61K49/00; A61K49/22; A61K49/222; A61K49/226; A61K49/223
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
27 words
A biocompatible ultrasound contrast agent including a liquid-in-liquid colloidal dispersion comprising a dispersed phase and an aqueous continuous phase, said dispersed phase comprising dodecafluoropentane and an amphiphile.
Claim 2
Dependent Claim
27 words
A biocompatible ultrasound contrast agent including a liquid-in-liquid colloidal dispersion comprising a dispersed phase and an aqueous continuous phase, said dispersed phase comprising dodecafluoropentane and an amphiphile.
Claim 3
Dependent Claim
14 words
The colloidal dispersion of claim 1 wherein said amphiphilic material comprises a biocompatible protein.
Claim 4
Dependent Claim
25 words
The colloidal dispersion of claim 2 wherein said protein is selected from the group consisting of albumin, fibrinogen, fibrin, serum globulins, hemoglobin, myoglobin, and immunoglobulins.
Claim 5
Dependent Claim
17 words
The colloidal dispersion of claim 1 wherein said amphiphilic material comprises a polyoxypropylene-polyoxyethylene glycol nonionic block copolymer.
Claim 6
Dependent Claim
14 words
The colloidal dispersion of claim 1 wherein said amphiphilic material comprises a fluorine-containing surfactant.
Claim 7
Dependent Claim
25 words
The colloidal dispersion of claim 1 wherein said amphiphilic material is selected from the group of surfactants consisting of anionic, cationic, nonionic, or zwitterionic molecules.
Claim 8
Dependent Claim
75 words
The colloidal dispersion of claim 1 wherein said amphiphilic material comprises at least one surfactant selected from the group of surfactants which contain, as hydrophilic groups, one or more of the following chemical groups: sulfonate, sulfate, carboxylate, phosphate, ammonium, quaternary ammonium, betaines, sulfobetaines, polyoxyethylene, polyols, alcohols, ethers, polypeptide, or polyglycidyl; and as hydrophobic groups, one or more of the following chemical groups: fatty acids, paraffins, olefins, alkyl benzenes, alcohols, alkylphenols, polyoxypropylenes, polypeptides, fluorocarbons, and silicones.
Claim 9
Dependent Claim
32 words
The colloidal dispersion of claim 1 wherein said amphiphilic material is present at a concentration such that the interfacial tension between water and the liquid dispersed phase is less than 26 dynes/cm.
Claim 10
Dependent Claim
23 words
The colloidal dispersion of claim 1 wherein said amphiphilic material is present at a concentration between 0.001% and 6.0% by weight per volume.
Claim 11
Dependent Claim
13 words
The colloidal dispersion of claim 1 wherein said dispersion further comprises a viscogen.
Claim 12
Dependent Claim
25 words
The colloidal dispersion of claim 10 wherein said viscogen is selected from the group consisting of glucose, iohexol, iopamidol, iopentol, sorbitol, sucrose, and polyethylene glycol.
Claim 13
Dependent Claim
23 words
The colloidal dispersion of claim 10 wherein the viscogen is present at a concentration sufficient to produce a viscosity greater than 1.1 cP.
Claim 14
Dependent Claim
23 words
The colloidal dispersion of claim 10 wherein the viscogen is present at a concentration of between 0.001 and 75% by weight per volume.
Claim 15
Dependent Claim
21 words
The colloidal dispersion of claim 1 wherein said liquid dispersed phase comprises particles having an average diameter less than 1000 nm.
Claim 16
Dependent Claim
23 words
The colloidal dispersion of claim 1 wherein the concentration of said liquid dispersed phase is between 0.00001 to 166% by weight per volume.
Claim 17
Dependent Claim
42 words
The colloidal dispersion of claim 1 wherein the aqueous medium comprises an additive selected from the group of acidifying agents, alkalizing agents, antimicrobial preservatives, antioxidants, buffering agents, chelating agents, complexing agents, solubilizing agents, hmectants, solvents, suspending agents, viscosity-increasing agents and tonicity agents.
Claim 18
Dependent Claim
27 words
The colloidal dispersion of claim 16 wherein said additive is present at a concentration such that the osmolarity of said aqueous medium is at least 250 mOm.
Claim 19
Dependent Claim
33 words
A biocompatible liquid-in-liquid colloidal dispersion for use in ultrasound imaging of an animal, said dispersion comprising an aqueous continuous phase and a water-immiscible dispersed phase, said dispersed phase including dodecafluoropentane and an amphiphile.
Claim 20
Dependent Claim
33 words
A biocompatible liquid-in-liquid colloidal dispersion for use in ultrasound imaging of an animal, said dispersion comprising an aqueous continuous phase and a water-immiscible dispersed phase, said dispersed phase including dodecafluoropentane and an amphiphile.
Claim 21
Independent Claim
91 words
A method of ultrasound imaging comprising the steps of: (1) preparing a stable, biocompatible liquid-in-liquid colloidal dispersion comprising an aqueous continuous phase and a water-immiscible dispersed phase, said dispersed phase comprising a perfluorocarbon wherein said perfluorocarbon is selected from the group consisting of perfluoropropane, perfluorobutane and perfluoropentane and an amphiphile; (2) administering said dispersion to an animal to be imaged; (3) waiting a time sufficient for said liquid dispersed phase to form microbubbles; and (4) performing an ultrasound scan on a portion of said animal in which said microbubbles are distributed.
Claim 22
Independent Claim
91 words
A method of ultrasound imaging comprising the steps of: (1) preparing a stable, biocompatible liquid-in-liquid colloidal dispersion comprising an aqueous continuous phase and a water-immiscible dispersed phase, said dispersed phase comprising a perfluorocarbon wherein said perfluorocarbon is selected from the group consisting of perfluoropropane, perfluorobutane and perfluoropentane and an amphiphile; (2) administering said dispersion to an animal to be imaged; (3) waiting a time sufficient for said liquid dispersed phase to form microbubbles; and (4) performing an ultrasound scan on a portion of said animal in which said microbubbles are distributed.
Claim 23
Dependent Claim
22 words
An ultrasound contrast agent according to claim 15, wherein the dispersed phase is present in a concentration of 0.05 to 5.0% w/v.
Claim 24
Dependent Claim
75 words
An ultrasound contrast agent comprising a liquid-in-liquid biocompatible colloidal dispersion containing a water immiscible dispersed phase and an aqueous continuous phase, said dispersed phase comprising at least one perfluorocarbon wherein said perfluorocarbon is selected from the group consisting of perfluoropropane, perfluorobutane and perfluoropentane and an amphiphilic material, wherein said dispersed phase is present in a concentration of 0.05 to 5.0% w/v, and said amphiphilic material is present at a concentration between 0.001 and 6.0% w/v.
Claim 25
Dependent Claim
75 words
An ultrasound contrast agent comprising a liquid-in-liquid biocompatible colloidal dispersion containing a water immiscible dispersed phase and an aqueous continuous phase, said dispersed phase comprising at least one perfluorocarbon wherein said perfluorocarbon is selected from the group consisting of perfluoropropane, perfluorobutane and perfluoropentane and an amphiphilic material, wherein said dispersed phase is present in a concentration of 0.05 to 5.0% w/v, and said amphiphilic material is present at a concentration between 0.001 and 6.0% w/v.
Claim 26
Dependent Claim
24 words
An ultrasound contrast agent comprising a liquid-in-liquid biocompatible colloidal dispersion containing a dispersed phase and an aqueous continuous phase, said dispersed phase comprising dodecafluoropentane.
Claim 27
Dependent Claim
24 words
An ultrasound contrast agent comprising a liquid-in-liquid biocompatible colloidal dispersion containing a dispersed phase and an aqueous continuous phase, said dispersed phase comprising dodecafluoropentane.
References Cited (Backward Citations)
DE410470C
Cited
US3898843A
Cited
WO1980002365A1
Cited
US4276885A
Cited
US4265251A
Cited
US4442843A
Cited
US4681119A
Cited
US4657756A
Cited
JPS57177790A
Cited
US4533254A
Cited
US4466442A
Cited
EP0077752A2
Cited
AU9170982A
Cited
JPS5967229A
Cited
US4572203A
Cited
US4718433A
Cited
US5141738A
Cited
US4544545A
Cited
US4900540A
Cited
US4767610A
Cited
US4859363A
Cited
US4684479A
Cited
US4832941A
Cited
US5155215A
Cited
US4774958A
Cited
US5080885A
Cited
US5393513A
Cited
US4987154A
Cited
US4865836A
Cited
US4927623A
Cited
EP0231091A1
Cited
EP0245019A2
Cited
US4895876A
Cited
US5354549A
Cited
EP0307087A1
Cited
US5284645A
Cited
EP0324938A1
Cited
US4844882A
Cited
WO1989006978A1
Cited
EP0327490A1
Cited
WO1989010118A1
Cited
US5171755A
Cited
US4993415A
Cited
EP0357163A1
Cited
US4957656A
Cited
EP0359246A2
Cited
DE3834705A1
Cited
WO1990007491A1
Cited
US5114703A
Cited
US5344930A
Cited
US5260496A
Cited
US5078146A
Cited
JPH02196730A
Cited
US5088499A
Cited
US5123414A
Cited
WO1991009629A1
Cited
WO1991012823A1
Cited
WO1991015244A2
Cited
US5271928A
Cited
EP0454044A2
Cited
US5137928A
Cited
EP0458745A1
Cited
WO1991018612A1
Cited
EP0467031A2
Cited
WO1992002560A1
Cited
WO1992005806A1
Cited
WO1992008496A1
Cited
EP0494615A1
Cited
DE4100470A1
Cited
EP0502814A2
Cited
US5107842A
Cited
WO1992015284A1
Cited
WO1992017213A1
Cited
WO1992017212A1
Cited
US5205290A
Cited
US5281408A
Cited
WO1992018165A2
Cited
WO1992018169A1
Cited
US5147631A
Cited
WO1992021382A1
Cited
WO1992022247A1
Cited
WO1993000933A1
Cited
WO1993000930A1
Cited
WO1993001798A1
Cited
DE4127442A1
Cited
WO1993005189A1
Cited
WO1993006869A1
Cited
WO1993007905A2
Cited
EP0554213A1
Cited
WO1993017718A1
Cited
US5401493A
Cited
US5385147A
Cited
US5406950A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-09-24 | 2000-03-25 | 2000-09-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-09-24 | 2004-03-25 | 2004-09-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-09-24 | 2008-03-25 | 2008-09-24 | $7700.00 | Window Closed / Lapsed |