DE3803971C1 - Ultrasound contrast medium - Google Patents

Ultrasound contrast medium

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Publication number
DE3803971C1
DE3803971C1 DE3803971A DE3803971A DE3803971C1 DE 3803971 C1 DE3803971 C1 DE 3803971C1 DE 3803971 A DE3803971 A DE 3803971A DE 3803971 A DE3803971 A DE 3803971A DE 3803971 C1 DE3803971 C1 DE 3803971C1
Authority
DE
Germany
Prior art keywords
ultrasound contrast
microparticles
contrast medium
methyl
medium according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
DE3803971A
Other languages
German (de)
Other versions
DE3803971C2 (en
Inventor
Dieter Heldmann
Michael Dr. Stein
Thomas Dr. Fritzsch
Joachim Dr. Siegert
Ulrich Prof. Dr. Speck
Georg Dr. 1000 Berlin De Roessling
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to DE3803971A priority Critical patent/DE3803971C2/en
Application filed by Schering AG filed Critical Schering AG
Priority to AU30351/89A priority patent/AU635200B2/en
Priority to AT89901933T priority patent/ATE109663T1/en
Priority to ES89901933T priority patent/ES2068917T3/en
Priority to JP1501696A priority patent/JP2907911B2/en
Priority to HU9601731A priority patent/HU9601731D0/en
Priority to IE34389A priority patent/IE66912B1/en
Priority to DE58908194T priority patent/DE58908194D1/en
Priority to EP89730021A priority patent/EP0327490A1/en
Priority to PCT/DE1989/000069 priority patent/WO1989006978A1/en
Priority to EP93112378A priority patent/EP0586875A1/en
Priority to EP89901933A priority patent/EP0398935B1/en
Priority to HU055/89A priority patent/HU221485B/en
Priority to KR1019890701826A priority patent/KR0133132B1/en
Priority to ZA89873A priority patent/ZA89873B/en
Priority to IE940809A priority patent/IE940809L/en
Priority to CA000590059A priority patent/CA1336164C/en
Priority to IL89175A priority patent/IL89175A/en
Priority to PT89635A priority patent/PT89635B/en
Priority to MYPI89000146A priority patent/MY105856A/en
Priority to CN89100726A priority patent/CN1033840C/en
Priority to NZ227869A priority patent/NZ227869A/en
Priority to NZ237900A priority patent/NZ237900A/en
Publication of DE3803971C1 publication Critical patent/DE3803971C1/en
Application granted granted Critical
Priority to US07/536,373 priority patent/US6264959B1/en
Priority to DK199001864A priority patent/DK175832B1/en
Priority to FI903865A priority patent/FI99086C/en
Priority to NO903443A priority patent/NO301260B1/en
Priority to US08/477,642 priority patent/US6071496A/en
Priority to US08/474,468 priority patent/US6177062B1/en
Priority to JP7306254A priority patent/JP3027326B2/en
Priority to NO970732A priority patent/NO304412B1/en
Publication of DE3803971C2 publication Critical patent/DE3803971C2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
    • A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
    • A61K49/228—Host-guest complexes, clathrates, chelates

Abstract

The invention provides an ultrasound contrast medium in which the gas-containing and/or gas-forming microparticles are composed of starch and/or starch derivatives and/or substances obtained therefrom.

Description

Die Erfindung betrifft ein Ultraschallkontrastmittel nach dem Oberbegriff des Patentanspruchs 1.The invention relates to an ultrasound contrast agent according to the preamble of claim 1.

Als Kontrastmittel werden in der medizinischen Ultraschalldiagnostik Gas enthaltende oder Gas produzie­ rende Substanzen verwendet (Roelandt, Contrast Echocardiography, Ultrasound Med Biol 8: 471-492, 1982). Daneben gibt es Ultraschallkontrastmittel in Form von Partikeln (Ophir, Gobuty, Mc Whirt, Maklad, Ultrasonic Backscatter from Contrast-producing Collagen Microspheres, Ultrasonic Imaging 2: 66-67, 1980). Ferner werden (Ophir, Mc Whirt, Maklad, Aqueous Solutions as Potential Ultrasonic Contrast Agents, Ultrasonic Imaging 1: 265-279, 1979 sowie Tyler, Ophir, Maklad, In-vivo Enhancement of Ultrasonic Image Luminance by Aqueous Solutions with High Speed of Sound, Ultrasonic Imaging 3: 323-329, 1981) oder es werden Lösungen höherer Dichte als Ultraschall-Kontrastmittel eingesetzt. Es ist auch bekannt, Emulsionen als Ultraschall-Kontrastmittel zu verwenden (Mattrey, Andre, Ultrasonic Enhancement of Myocardial Infarction with Perfluorcarbon Compounds in Dogs, Am J Cardiol 54: 206-210, 1984).As a contrast medium in medical Ultrasound diagnostics containing gas or gas produzie substances (Roelandt, Contrast Echocardiography, Ultrasound Med Biol 8: 471-492, 1982). There are also ultrasound contrast agents in the form of Particles (Ophir, Gobuty, Mc Whirt, Maklad, Ultrasonic Backscatter from Contrast-producing collages Microspheres, Ultrasonic Imaging 2: 66-67, 1980). Further (Ophir, Mc Whirt, Maklad, Aqueous Solutions as Potential Ultrasonic Contrast Agents, Ultrasonic Imaging 1: 265-279, 1979 and Tyler, Ophir, Maklad, in vivo Enhancement of Ultrasonic Image Luminance by Aqueous Solutions with High Speed of Sound, Ultrasonic Imaging 3: 323-329, 1981) or higher density solutions used as an ultrasound contrast medium. It is also known to emulsions as ultrasound contrast agents use (Mattrey, Andre, Ultrasonic Enhancement of Myocardial Infarction with Perfluorcarbon Compounds in Dogs, Am J Cardiol 54: 206-210, 1984).

Es hat sich gezeigt, daß die gasfreien Kontrastmittel insgesamt nur eine geringe Effizienz besitzen. Die gas­ haltigen Zubereitungen haben den Nachteil einer nur ge­ ringen in-vivo Stabilität. Darüber hinaus ist die Größe der Gasblasen zu meist nicht standardisierbar. Aus­ reichende Kontrasteffekte sind im arteriellen Gefäß­ system nach peripher venöser Injektion in aller Regel nicht möglich.It has been shown that the gas-free contrast agents overall have low efficiency. The gas Prepared preparations have the disadvantage of only one  wrestle in vivo stability. In addition, the size the gas bubbles are mostly not standardized. Off sufficient contrast effects are in the arterial vessel system after peripheral venous injection as a rule not possible.

In den EP A2 1 23 235 und 01 22 624 werden Gasbläschen enthaltende Ultraschall-Kontrastmittel beschrieben, die die Lungenkapillaren passieren können und damit den ge­ wünschten Kontrasteffekt bewirken.EP A2 1 23 235 and 01 22 624 describe gas bubbles containing ultrasound contrast agents described that can pass through the lung capillaries and thus the ge desired effect of contrast.

Die EP A2 02 24 934 beschreibt Ultraschall-Kontrast­ mittel in Form von gasgefüllten Gelantine- oder Albumin­ hohlkörpern. Nachteilig ist jedoch die Verwendung von körperfremden Eiweißen und das damit verbundene aller­ gene Risiko sowie die Emboliegefahr. Das sich die dena­ turierten Proteine im Körper nicht auflösen, sondern langsam abgebaut werden, besteht die Gefahr, daß es zur Verlegung von Arteriolen oder Kapillaren beispielsweise im cerebralen Bereich kommt.EP A2 02 24 934 describes ultrasound contrast medium in the form of gas-filled gelatin or albumin hollow bodies. However, the use of is disadvantageous foreign proteins and all of them risk and the risk of embolism. That dena not dissolve turiated proteins in the body, but are slowly broken down, there is a risk that it will Laying arterioles or capillaries, for example comes in the cerebral area.

Der Erfindung liegt die Aufgabe zugrunde, ein neues für den Menschen gut verträgliches Ultraschallkontrastmittel zur Verfügung zu stellen.The invention has for its object a new for ultrasound contrast medium that is well tolerated by humans to provide.

Diese Aufgabe wird durch Mikropartikel nach dem Pa­ tentanspruch 1 gelöst.This task is carried out by microparticles according to Pa Claim 1 solved.

Mit besonderem Vorteil enthalten die Mikropartikel eine organische Flüssigkeit oder ein Lösungsmittel mit einem Siedepunkt unter 60°C, insbesondere wenigstens eines der folgenden organischen Flüssigkeiten und/oder Lösungsmittel:The microparticles contain a particularly advantageous one organic liquid or a solvent with a Boiling point below 60 ° C, especially at least one  the following organic liquids and / or Solvent:

1,1-Dichlorethylen
2-Methyl-2-Buten
Isopropylchlorid
2-Methyl-1,3-Butadien
2-Butin
2-Methyl-1-Buten
Dibromdifluormethan
Furan
3-Methyl-1-Buten
Isopentan
Diethylether
3,3-Dimethyl-1-Butin
Dimethylaminoaceton
Propylenoxid
N-Ethylmethylamin
Brommethan
N-Ethyldimethylamin
Methylenchlorid1,1-dichlorethylene
2-methyl-2-butene
Isopropyl chloride
2-methyl-1,3-butadiene
2-butyne
2-methyl-1-butene
Dibromodifluoromethane
Furan
3-methyl-1-butene
Isopentane
Diethyl ether
3,3-dimethyl-1-butyne
Dimethylaminoacetone
Propylene oxide
N-ethylmethylamine
Bromomethane
N-ethyldimethylamine
Methylene chloride

Als gasförmige Komponente enthalten die Mikropartikel mindestens ein Gas der folgenden GruppeThe microparticles contain as a gaseous component at least one gas from the following group

Stickstoff
Krypton
Xenon
Sauerstoff
Kohlendioxid
Ethylen
Methan
Ethan
Propan
Butannitrogen
krypton
xenon
oxygen
Carbon dioxide
Ethylene
methane
Ethan
propane
butane

Mit Vorteil können die Mikropartikel auch Substanzen mit niedrigen Dampfdrücken und/oder niedrigen Siedepunkten, insbesondere ätherische Öle enthalten.The microparticles can also advantageously contain substances low vapor pressures and / or low boiling points, in particular contain essential oils.

Besonders vorteilhaft ist es, die Mikropartikel mit einer Hüllsubstanz zu überziehen. Dabei können die Mikropartikel von Ölen, Fetten und/oder oberflächenak­ tiven Substanzen umhüllt und in wäßrigem Medium emul­ giert sein.It is particularly advantageous to use the microparticles to coat an enveloping substance. The Microparticles of oils, fats and / or surface ac tive substances enveloped and emulsified in aqueous medium be greedy.

Besonders vorteilhaft ist es, die Mikropartikel mit einer Matrix, insbesondere polymerer Struktur zu um­ hüllen.It is particularly advantageous to use the microparticles a matrix, in particular a polymeric structure envelop.

Durch Zugabe osmotisch aktiver Substanzen, insbesondere Kochsalz, Galaktose, Glukose, Fruktose kann die physio­ logische Isotonie eingestellt werden.By adding osmotically active substances, in particular Saline, galactose, glucose, fructose can be the physio logical isotonicity can be set.

Beispiel 1example 1 β-Cyclodextrin-Isopentan-Einschlußverbindung β- cyclodextrin isopentane inclusion compound

100 ml gesättigte β-Cyclodextrin-Lösung (1,8%ig) wird bei 10°C gekühlt und mit 3 ml Isopentan versetzt. Unter ständigem Rühren im Ultraschallbad wird der entstehende schwerlösliche Komplex ausgefällt. Durch Gefriertrocknen und Filtrieren wird der Niederschlag in kristalliner Form erhalten. Isopentangehalt nach GC-Bestimmung: 0,26%.100 ml of saturated β- cyclodextrin solution (1.8%) is cooled at 10 ° C. and 3 ml of isopentane are added. The resulting poorly soluble complex is precipitated with constant stirring in an ultrasonic bath. The precipitate is obtained in crystalline form by freeze-drying and filtering. Isopentane content according to GC determination: 0.26%.

Beispiel 2Example 2 β-Cyclodextrin-2-Methyl-2-Buten-Einschlußverbindung β- Cyclodextrin-2-methyl-2-butene inclusion compound

100 ml gesättigte β-Cyclodextrin-Lösung (1,8%ig) wird bei 10°C gekühlt und mit 3 ml 2-Methyl-2-Buten ver­ setzt. Unter ständigem Rühren im Ultraschallbad wird der entstehende schwerlösliche Komplex ausgefällt. Durch Gefriertrocknen und Filtrieren wird der Niederschlag in kristalliner Form erhalten.100 ml of saturated β- cyclodextrin solution (1.8%) is cooled at 10 ° C. and mixed with 3 ml of 2-methyl-2-butene. The resulting poorly soluble complex is precipitated with constant stirring in an ultrasonic bath. The precipitate is obtained in crystalline form by freeze-drying and filtering.

Beispiel 3Example 3 β-Cyclodextrin-2-Methyl-1-Buten-Einschlußverbindung β- Cyclodextrin-2-methyl-1-butene inclusion compound

100 ml gesättigte β-Cyclodextrin-Lösung (1,8%ig) wird bei 10°C gekühlt und mit 3 ml 2-Methyl-1-Buten ver­ setzt. Unter ständigem Rühren im Ultraschallbad wird der entstehende schwerlösliche Komplex ausgefällt. Durch Gefriergetrocknen und Filtrieren wird der Niederschlag in kristalliner Form erhalten. 2-Methyl-1-Buten-Gehalt nach GC-Bestimmung: 0,82%.100 ml of saturated β- cyclodextrin solution (1.8%) is cooled at 10 ° C. and mixed with 3 ml of 2-methyl-1-butene. The resulting poorly soluble complex is precipitated with constant stirring in an ultrasonic bath. The precipitate is obtained in crystalline form by freeze-drying and filtering. 2-methyl-1-butene content according to GC determination: 0.82%.

Beispiel 4Example 4 β-Cyclodextrin-Isopren-Einschlußverbindung β- cyclodextrin isoprene inclusion compound

100 ml gesättigte β-Cyclodextrin-Lösung (1,8%ig) wird bei 10°C gekühlt und mit 3 ml Isopren versetzt. Unter ständigem Rühren im Ultraschallbad wird der entstehende schwerlösliche Komplex ausgefällt. Durch Gefrierge­ trocknung und Filtrieren wird der Niederschlag in kristalliner Form erhalten. Isoprengehalt nach GC- Bestimmung: 1,0%.100 ml of saturated β- cyclodextrin solution (1.8%) is cooled at 10 ° C. and mixed with 3 ml of isoprene. The resulting poorly soluble complex is precipitated with constant stirring in an ultrasonic bath. Freeze drying and filtering give the precipitate in crystalline form. Isoprene content according to GC determination: 1.0%.

Beispiel 5Example 5 β-Cyclodextrin-Isopropylchlorid-Einschlußverbindung β- cyclodextrin isopropyl chloride inclusion compound

100 ml gesättigte β-Cyclodextrin-Lösung (1,8%ig) wird bei 10°C gekühlt und mit 3 ml Isopropylchlorid ver­ setzt. Unter ständigem Rühren im Ultraschallbad wird der entstehende schwerlösliche Komplex ausgefällt. Durch Gefriertrocknen und Filtrieren wird der Niederschlag in kristalliner Form erhalten. Isopropylchloridgehalt nach GC-Bestimmung: 0,5%.100 ml of saturated β- cyclodextrin solution (1.8%) is cooled at 10 ° C. and mixed with 3 ml of isopropyl chloride. The resulting poorly soluble complex is precipitated with constant stirring in an ultrasonic bath. The precipitate is obtained in crystalline form by freeze-drying and filtering. Isopropyl chloride content according to GC determination: 0.5%.

Beispiel 6Example 6 β-Cyclodextrin-Isopentan-Einschlußverbindung β- cyclodextrin isopentane inclusion compound

100 ml gesättigte β-Cyclodextrin-Lösung (1,8%ig) wird bei 10°C gekühlt und mit 20 mg Isopentan versetzt. Unter ständigem Rühren im Ultraschallbad wird der entstehende schwerlösliche Komplex ausgefällt. Durch Gefriertrocknen und Filtrieren wird der Niederschlag in kristalliner Form erhalten. 100 ml of saturated β- cyclodextrin solution (1.8%) is cooled at 10 ° C. and 20 mg of isopentane are added. The resulting poorly soluble complex is precipitated with constant stirring in an ultrasonic bath. The precipitate is obtained in crystalline form by freeze-drying and filtering.

Beispiel 7Example 7 Xenonid-Cyclodextrin-EinschlußverbindungenXenonide cyclodextrin inclusion compounds

In einem 200 cm3 Autoklaven werden 100 ml gesättigte α- Cyclodextrin-Lösung (ca. 12%ig) unter 7 Atmosphären 7 Tage lang bei Zimmertemperatur inkubiert. Das kristal­ line Addukt kann abgesaugt, mit kaltem Wasser gewaschen und im Exsikkator über CaCl2 getrocknet werden.In a 200 cm 3 autoclave, 100 ml of saturated α -cyclodextrin solution (approx. 12%) are incubated under 7 atmospheres for 7 days at room temperature. The crystalline line adduct can be filtered off, washed with cold water and dried over CaCl 2 in a desiccator.

Beispiel 8Example 8 CO2-α-Cyclodextrin-EinschlußverbindungCO2- α- cyclodextrin inclusion compound

In einem 200 cm3 Autoklaven werden 100 ml gesättigte α- Cyclodextrin-Lösung (ca. 12%ig) unter 7 Atmosphären 7 Tage lang bei Zimmertemperatur inkubiert. Das kristalline Addukt kann abgesaugt, mit kaltem Wasser gewaschen und im Exsikkator über CaCl2 getrocknet werden.In a 200 cm 3 autoclave, 100 ml of saturated α -cyclodextrin solution (approx. 12%) are incubated under 7 atmospheres for 7 days at room temperature. The crystalline adduct can be filtered off, washed with cold water and dried over CaCl 2 in a desiccator.

Beispiel 9Example 9 Isopentan-Hydroxypropyl-β-Cyclodextrin-EinschlußverbindungIsopentane-hydroxypropyl- β- cyclodextrin inclusion compound

15 ml 20%ige Hydroxypropyl-β-Cyclodextrin-Lösung werden bei 10°C mit 2 ml Isopentan versetzt, im Ultraschallbad 3 min beschallt und danach für 26 Stunden inkubiert. Der entstandene Komplex bleibt in Lösung.15 ml of 20% hydroxypropyl- β- cyclodextrin solution are mixed with 10 ml of isopentane at 10 ° C., sonicated in an ultrasonic bath for 3 minutes and then incubated for 26 hours. The resulting complex remains in solution.

Beispiel 10Example 10 Isopren-Hydroxypropyl-β-Cyclodextrin-EinschlußverbindungIsoprene-hydroxypropyl- β- cyclodextrin inclusion compound

15 ml 20%ige Hydroxypropyl-β-Cyclodextrin-Lösung werden bei 10°C mit 2 ml Isopren versetzt, im Ultraschallbad 3 min beschallt und danach für 26 Stunden inkubiert. Der ent­ standene Komplex bleibt zum Teil in Lösung und fällt zu einem Teil als weißer Niederschlag aus.15 ml of 20% hydroxypropyl- β- cyclodextrin solution are mixed with 2 ml of isoprene at 10 ° C., sonicated for 3 minutes in an ultrasonic bath and then incubated for 26 hours. The resulting complex remains partly in solution and partly precipitates as a white precipitate.

Beispiel 11Example 11 Furan-Hydroxypropyl-β-Cyclodextrin-EinschlußverbindungFuran-hydroxypropyl- β- cyclodextrin inclusion compound

15 ml 20%ige Hydroxypropyl-β-Cyclodextrin-Lösung wurden bei 10°C mit 2 ml Furan versetzt, im Ultraschallbad 3 min be­ schallt und danach für 26 Stunden inkubiert. Der ent­ standene Komplex bleibt zum Teil in Lösung und fällt zu einem Teil als weißer Niederschlag aus.15 ml of 20% hydroxypropyl- β- cyclodextrin solution were mixed with 10 ml of furan at 10 ° C., sonicated for 3 minutes in an ultrasonic bath and then incubated for 26 hours. The resulting complex remains partly in solution and partly precipitates as a white precipitate.

Beispiel 12Example 12 Isopentan-α-Cyclodextrin-EinschlußverbindungIsopentane α- cyclodextrin inclusion compound

20 ml gesättigte α-Cyclodextrin-Lösung werden mit 1 ml Isopentan versetzt und im Ultraschallbad 3 min beschallt. Der entstehende schwerlösliche Komplex wird durch Filtration gewonnen und über CaCl2 getrocknet.20 ml of saturated α- cyclodextrin solution are mixed with 1 ml of isopentane and sonicated for 3 minutes in an ultrasonic bath. The resulting poorly soluble complex is collected by filtration and dried over CaCl 2 .

Beispiel 13Example 13 Isopren-α-Cyclodextrin-EinschlußverbindungIsoprene- α- cyclodextrin inclusion compound

20 ml gesättigte α-Cyclodextrin-Lösung werden mit 1 ml Isopren versetzt und im Ultraschallbad 3 min beschallt. Der ent­ stehende schwerlösliche Komplex wird durch Filtration gewonnen und über CaCl2 getrocknet.20 ml of saturated α- cyclodextrin solution are mixed with 1 ml of isoprene and sonicated in an ultrasound bath for 3 minutes. The resulting sparingly soluble complex is collected by filtration and dried over CaCl 2 .

Beispiel 14Example 14 Furan-α-Cyclodextrin-EinschlußverbindungFuran α- cyclodextrin inclusion compound

20 ml gesättigte α-Cyclodextrin-Lösung werden mit 1 ml Furan ver­ setzt und im Ultraschallbad 3 min beschallt. Der ent­ stehende schwerlösliche Komplex wird durch Filtration gewonnen und über CaCl2 getrocknet.20 ml of saturated α- cyclodextrin solution are mixed with 1 ml of furan and sonicated for 3 minutes in an ultrasonic bath. The resulting sparingly soluble complex is collected by filtration and dried over CaCl 2 .

Für alle Mittel gilt:The following applies to all means:

Der kristalline Niederschlag wird nach dem Reinigen in einem geeigneten wäßrigen Medium, vorzugsweise physiolo­ gischer Kochsalz-, Glukose- oder Ringerlösung aufge­ nommen und ist dann injektionsfertig. Nach der Injektion entstehen Gasblasen geeigneter Größe.The crystalline precipitate is after cleaning in a suitable aqueous medium, preferably physiolo gisch saline, glucose or Ringer solution taken and is then ready for injection. After the injection gas bubbles of a suitable size are formed.

Claims (7)

1. Ultraschallkontrastmittel bestehend aus gasent­ haltenden und/oder gasfreisetzenden Mikropartikeln, dadurch gekennzeichnet, daß die Mikropartikel aus Cyclodextrinen oder Cyclodextrinderivaten und einem Gas und/oder einer organischen Flüssigkeit mit einem Siedepunkt unter 60°C bestehen. 1. Ultrasound contrast medium consisting of gas-containing and / or gas-releasing microparticles, characterized in that the microparticles consist of cyclodextrins or cyclodextrin derivatives and a gas and / or an organic liquid with a boiling point below 60 ° C. 2. Ultraschallkontrastmittel nach Anspruch 1, dadurch gekennzeichnet, daß die Mikropartikel wenigstens eine der folgenden organischen Flüssigkeiten mit einem Siedepunkt unter 60°C enthalten:
1,1-Dichlorethylen
2-Methyl-2-Buten
Isopropylchlorid
2-Methyl-1,3-Butadien
2-Butin
2-Methyl-1-Buten
Dibromdifluormethan
Furan
3-Methyl-1-Buten
Isopentan
Diethylether
3,3-Dimethyl-1-Butin
Dimethylaminoaceton
Propylenoxid
N-Ethylmethylamin
Brommethan
N-Ethyldimethylamin
Methylenchlorid 2. Ultrasound contrast medium according to claim 1, characterized in that the microparticles contain at least one of the following organic liquids with a boiling point below 60 ° C:
1,1-dichlorethylene
2-methyl-2-butene
Isopropyl chloride
2-methyl-1,3-butadiene
2-butyne
2-methyl-1-butene
Dibromodifluoromethane
Furan
3-methyl-1-butene
Isopentane
Diethyl ether
3,3-dimethyl-1-butyne
Dimethylaminoacetone
Propylene oxide
N-ethylmethylamine
Bromomethane
N-ethyldimethylamine
Methylene chloride 3. Ultraschallkontrastmittel nach Anspruch 1, dadurch gekennzeichnet, daß
die Mikropartikel als Gase
Stickstoff,
Krypton,
Xenon,
Sauerstoff,
Kohlendioxid,
Ethylen,
Methan,
Ethan,
Propan oder
Butan
oder deren Gemische enthalten.3. Ultrasound contrast medium according to claim 1, characterized in that
the microparticles as gases
Nitrogen,
Krypton,
Xenon,
Oxygen,
Carbon dioxide,
Ethylene,
Methane,
Ethan,
Propane or
butane
or contain mixtures thereof. 4. Ultraschallkontrastmittel nach Anspruch 1, dadurch gekennzeichnet, daß die Mikropartikel ätherische Öle enthalten.4. ultrasound contrast medium according to claim 1, characterized in that the microparticles contain essential oils. 5. Ultraschallkontrastmittel nach mindestens einem der Ansprüche 1-4, dadurch gekennzeichnet, daß die Mikropartikel mit einer hydrophoben Hüllsubstanz bestehend aus Ölen, Fetten und/oder oberflächenakti­ ven Substanzen überzogen und in wäßrigem Medium emul­ giert sind.5. Ultrasound contrast agent according to at least one of the Claims 1-4, characterized in that  the microparticles with a hydrophobic coating substance consisting of oils, fats and / or surface stocks ven substances coated and emulsified in aqueous medium are greeded. 6. Ultraschallkontrastmittel nach Anspruch 5, dadurch gekennzeichnet, daß die Mikropartikel von einer Matrix, insbesondere polymerer Struktur, umhüllt sind.6. ultrasound contrast medium according to claim 5, characterized in that the microparticles from a matrix, in particular polymeric structure, are encased. 7. Ultraschallkontrastmittel nach Anspruch 1 oder 5, dadurch gekennzeichnet, daß durch Zugabe osmotisch aktiver Substanzen, insbe­ sondere Kochsalz, Galaktose, Glukose, Fruktose, die physiologische Isotonie eingestellt ist.7. ultrasound contrast medium according to claim 1 or 5, characterized in that by adding osmotically active substances, in particular special table salt, galactose, glucose, fructose, the physiological isotonia is set.
DE3803971A 1988-02-05 1988-02-05 Ultrasound contrast media Expired - Lifetime DE3803971C2 (en)

Priority Applications (31)

Application Number Priority Date Filing Date Title
DE3803971A DE3803971C2 (en) 1988-02-05 1988-02-05 Ultrasound contrast media
AT89901933T ATE109663T1 (en) 1988-02-05 1989-02-01 ULTRASONIC CONTRAST AGENT, PROCESS FOR THEIR PREPARATION AND THEIR USE AS DIAGNOSTICS AND THERAPEUTICS.
ES89901933T ES2068917T3 (en) 1988-02-05 1989-02-01 CONTRAST MEANS BY ULTRASOUND, PROCEDURE FOR THEIR OBTAINING AND USE OF THEM AS DIAGNOSTIC AND THERAPEUTIC PRODUCTS.
JP1501696A JP2907911B2 (en) 1988-02-05 1989-02-01 Ultrasound contrast agent, method for producing the same, and diagnostic or therapeutic preparation comprising the ultrasound contrast agent
AU30351/89A AU635200B2 (en) 1988-02-05 1989-02-01 Ultrasonic contrast agents, process for producing them and their use as diagnostic and therapeutic agents
IE34389A IE66912B1 (en) 1988-02-05 1989-02-01 Ultrasonic contrast agents process for their preparation and their use as diagnostic and therapeutic agents
DE58908194T DE58908194D1 (en) 1988-02-05 1989-02-01 ULTRASONIC CONTRAST AGENTS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS DIAGNOSTICS AND THERAPEUTICS.
EP89730021A EP0327490A1 (en) 1988-02-05 1989-02-01 Ultrasonic imaging agents, process for their preparation and their diagnostic and therapeutical use
PCT/DE1989/000069 WO1989006978A1 (en) 1988-02-05 1989-02-01 Ultrasonic contrast agents, process for producing them and their use as diagnostic and therapeutic agents
EP93112378A EP0586875A1 (en) 1988-02-05 1989-02-01 Ultrasonic contrast agents, process for producing them and their use as diagnostic and therapeutic agents
EP89901933A EP0398935B1 (en) 1988-02-05 1989-02-01 Ultrasonic contrast agents, process for producing them and their use as diagnostic and therapeutic agents
HU055/89A HU221485B (en) 1988-02-05 1989-02-01 Ultrasound contrast media consisting of microparticles and process for producing the same
KR1019890701826A KR0133132B1 (en) 1988-02-05 1989-02-01 Ultrasonic contrast agents, process for producing them and their use as diagnostics
HU9601731A HU9601731D0 (en) 1988-02-05 1989-02-01 Ultrasonic contrastmaterials, process for producing them and their use as diagnostics and therapeutical materials
PT89635A PT89635B (en) 1988-02-05 1989-02-03 PROCESS FOR THE PREPARATION OF CONTRASTS FOR ULTRASSONS
IE940809A IE940809L (en) 1988-02-05 1989-02-03 Ultrasonic contrast agents, process for their preparation¹and their use as diagnostic and therapeutic agents
ZA89873A ZA89873B (en) 1988-02-05 1989-02-03 Ultrasonic contrast agents,process for their preparation and their use as a diagnostic and therapeutic agent
CA000590059A CA1336164C (en) 1988-02-05 1989-02-03 Ultrasonic contrast agents, process for their preparation and their use as a diagnostic and therapeutic agent
IL89175A IL89175A (en) 1988-02-05 1989-02-03 Ultrasonic contrast agents and processes for the preparation thereof
MYPI89000146A MY105856A (en) 1988-02-05 1989-02-04 Ultra sonic contrast agents, process for their preparation and their use as diagnostic and therapeutic agents.
CN89100726A CN1033840C (en) 1988-02-05 1989-02-04 Ultrasonic contrast medium and application for diagnosis treatment
NZ227869A NZ227869A (en) 1988-02-05 1989-02-07 Ultrasonic contrast agents containing amylose microparticles
NZ237900A NZ237900A (en) 1988-02-05 1989-02-07 Microparticles suitable as ultrasonic contrast agent comprising biodegradable polymers; preparation thereof
US07/536,373 US6264959B1 (en) 1988-02-05 1990-06-11 Ultrasonic contrast agents, process for their preparation and their use as a diagnostic and therapeutic agent
DK199001864A DK175832B1 (en) 1988-02-05 1990-08-03 Ultrasonic contrast agents and methods for their preparation and their use
FI903865A FI99086C (en) 1988-02-05 1990-08-03 Ultrasound contrast agents, methods for their preparation and their use as diagnostic agents
NO903443A NO301260B1 (en) 1988-02-05 1990-08-06 Ultrasonic contrast agents and their use in the manufacture of a preparation for ultrasound diagnostics
US08/477,642 US6071496A (en) 1988-02-05 1995-06-07 Polyalkylcyanoacrylate agents and methods for enhancing contrast in ultrasound imaging
US08/474,468 US6177062B1 (en) 1988-02-05 1995-06-07 Agents and methods for enhancing contrast in ultrasound imaging
JP7306254A JP3027326B2 (en) 1988-02-05 1995-11-24 Ultrasound contrast agent and ultrasonic diagnostic preparation
NO970732A NO304412B1 (en) 1988-02-05 1997-02-17 Ultrasonic contrast agent and its use in the manufacture of a composition for ultrasound diagnostics

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