Semifluorocarbon Compound Containing Contrast Agent

Patent metadata

Field	Value
Publication number	US-2016000941-A1
Application number	US-201414759444-A
Country	US
Kind code	A1
Filing date	Mar 18, 2014
Priority date	Mar 25, 2013
Publication date	Jan 7, 2016
Grant date	—

Abstract

The present invention relates to an aqueous emulsion comprising a) a semifluorinated compound of formula I: CF 3 —(CF 2 ) x —(CH 2 ) y —CH 3 (I) wherein x is an integer ranging from 1 to 8 and y is an integer ranging from 2 to 10, b) a triglyceride which is miscible with the semifluorinated compound at 20° C.; and c) an emulsifier.

First claim

1 . Aqueous emulsion comprising
a) a semifluorinated compound of formula I:
CF 3 —(CF 2 ) x —(CH 2 ) y —CH 3   (I)

wherein x is an integer ranging from 1 to 8 and y is an integer ranging from 2 to 10, b) a triglyceride which is miscible with the semifluorinated compound at 20° C.; and c) an emulsifier.

2 . Emulsion according to claim 1 wherein the semifluorinated compound is perfluorohexyloctane (F6H8) and/or perfluorbutylpentane (F4H5).

3 . Emulsion according to claim 1 , wherein the amount of the semifluorinated carbon compound a) and the triglyceride b), which is preferable a mid-chain triglyceride, ranges from 5 to 40 wt.-%, preferably 10 to 30 wt.-%, especially 15 to 25 wt-%, based on the total weight of the emulsion.

4 . Emulsion according to claim 1 , wherein the weight ratio of the semifluorinated carbon compound a) to the triglyceride b), which is preferably a mid-chain triglyceride (MCT), ranges from 1:20 to 1:0.20, preferably 1:15 to 1:0.25, more preferably 1:10 to 1:0.30, further preferably 1:4 to 1:0.35, especially 1:2 to 1:0.4.

5 . Emulsion according to claim 1 for use as a contrast agent or contrast enhancing agent.

6 . Emulsion according to claim 1 for use as a contrast enhancement agent or contrast agent for the diagnostic detection, by means of an imaging procedure utilizing MR-techniques.

7 . Emulsion according to claim 1 for use in the diagnostic detection, by means of an imaging procedure, of inflammatory processes selected from the group consisting of inflammatory reaction peripheral to infarctions such as myocardial infarction, stroke; inflammation of organs, such as myocarditis, encephalitis, meningitis; multiple sclerosis; inflammation of the gastrointestinal tract, such as Crohn's disease; inflammation of the vessels, such as arteriosclerosis, in particular vulnerable plaques; detection of abscesses and also arthritis, wherein the imaging process is based on measuring the nuclear magnetic resonance of the 19 F isotope.

8 . Emulsion according to claim 1 for use in the diagnostic detection, based on non-invasive imaging procedures of the cardio-vascular system, including the myocardium, arteries and veins; inflammatory reactions occurring in disease processes like myocardial infarction, myocarditis, atherosclerosis and thrombosis leading to inflammatory and degenerative processes of the vasculature found in neurology such as stroke or tumor; pulmology such as thrombosis, inflammation, sarcoidosis; gastroenterology such as tumour, inflammatory bowl diseases such as Crohn's disease; and rheumatology such as autoimmune diseases of the vessels such as Takayasu arteritis.

9 . Use of the emulsion according to claim 1 in a magnetic resonance imaging procedure.

10 . Method for the manufacturing of the emulsion according to claim 1 comprising the steps:
a) preparing a mixture by mixing
a semifluorinated compound of formula I:
CF 3 —(CF 2 ) x —(CH 2 ) y —CH 3   (I)

wherein x is an integer ranging from 1 to 8 and y is an integer ranging from 2 to 10,
a triglyceride which is miscible with the semifluorinated compound at 20° C.,
an emulsifier; and
water

b) homogenizing the mixture obtained in step a); and
c) optionally sterilizing the emulsion.

11 . Method according to claim 10 comprising the following steps:
a) preparing a mixture by
a-1) preparing a mixture comprising water and an emulsifier,
a-2) preparing a homogenous mixture comprising the semifluorinated compound and the triglyceride,
a-3) combining the mixture obtained in step a-1) with the mixture obtained in step a-2); and

b) homogenizing the mixture obtained in step a), preferably homogenizing the mixture obtained in step a) with a high pressure homogenizer.

12 . Method for operating a magnetic resonance tomograph for the detection of a semifluorinated compound of formula I:
CF 3 13 (CF 2 ) x —(CH 2 ) y —CH 3   (I)
wherein x is an integer ranging from 1 to 8 and y is an integer ranging from 2 to 10, in an emulsion as defined in claim 1 , the method comprising the method steps:
emitting an alternating magnetic field,
detecting an absorption of the emitted magnetic field by a sample to be examined,
characterized in that the frequency of the alternating magnetic field is between H 40.05650 MHz/T and H 40.06150 MHz/T, H being the magnetic field strength in Tesla.

13 . Method for detecting in a sample to be examined a semifluorinated compound of formula I:
CF 3 —(CF 2 ) x —(CH 2 ) y —CH 3   (I)
wherein x is an integer ranging from 1 to 8 and y is an integer ranging from 2 to 10 in an emulsion according to claim 1 , the method comprising the following method steps:
emitting an alternating magnetic field,
detecting an absorption of the emitted magnetic field by a sample to be examined,
characterized by the following method steps:
superimposing at least one 19 F-fluorine proton image over a 1 H proton image,
whereby the protons of 1 H image is displayed as a grey scale image and the protons of 19 F fluorine image is displayed by using a color gradient, one end of this color gradient indicating a low concentration of 19 F and the other end of this color gradient indicating a high concentration of 19 F.

14 . Method according to claim 13 characterized by the following method steps:
eliminating disturbing signals generated by 19 F fluorine protons in a second sample not to be examined by the following method steps:
comparing the value for the fluorine concentration in a first pixel with values of all pixels in the three-dimensional space around this first pixel,

whereby, if the difference between the values for the fluorine concentration of two adjacent pixels lies below a threshold these two pixels are considered to belong to a cluster of pixels,
removing this disturbing cluster of pixels from the image obtained, if the cluster does not represent the sample to be examined.

15 . Method comprising acquiring non-invasive imaging procedures of a patient to whom the emulsion according to claim 1 has previously administered so as to dissolve it in the patient's bloodstream.

Assignees

• Braun Melsungen Ag

Inventors

• Keller Thorsten
• Rothlein Doris
• Schmitt Jurgen
• Dietrich Thore
• Stawowy Philipp
• Fleck Eckart

Classifications

• A61K49/1806 Primary

  Suspensions, emulsions, colloids, dispersions · CPC title

• A61K49/10 Primary

  Organic compounds · CPC title

• G01R33/5601

  involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent · CPC title

• A61B5/055

  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging · CPC title

• A61K49/18

  characterised by a special physical form, e.g. emulsions, microcapsules, liposomes · CPC title