Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1995-05-12
1997-10-14
Kight, John
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
424 93, 424 91, A61K 4900, G01N 3100, G01N 3348
Patent
active
056769270
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
The present invention relates to contrast agents for MRI (Magnetic Resonance Imaging).
2. Background Art
Clinical applications of MRI have rapidly developed from the beginning of the 1980's, since its first application in the medical field in the early 1970's. MRI is now regarded as an important noninvasive image-forming technique, comparable with X-rays, computed tomography (X-ray CT) and ultrasonic diagnosis. MRI provides images based on nuclear magnetic resonance signals of protons in tissues of living organisms. Since it permits a high freedom in image forming and has high resolution, it was originally considered that contrast agents were not necessary. However, as clinical experience has been accumulated, certain drawbacks and limitations of MRI have come to light, and therefore, various contrast agents for MRI have been developed to provide a clear contrast between the normal tissue and the diseased part.
Contrast agents for MRI are divided into groups of positive contrast agents which intensify signal intensities by shortening the longitudinal relaxation time of protons, and negative contrast agents which weaken signal intensities by shortening the transverse relaxation time of protons. Paramagnetic metal ions belong to the former group, typical examples of which include chelating compounds of gadolinium such as magnebiste.
On the other hand, ferromagnetic particles belong to the latter group. When magnetic particles are administered to a subject orally or per rectum in the MRI diagnosis, artifacts caused by gas or the like in the digestive tract and peristalsis of the digestive tract can be minimized by rendering the digestive tract as a dark image. Therefore, the quality of image diagnosis in the abdominal organs can be enhanced by intensifying the contrast between the digestive tract and the target organ (Japanese patent application laid-open (kokai) SHO 61-501633).
Concerning preparations containing ferromagnetic particles, dispersions prepared by suspending ferromagnetic particles in an aqueous medium containing a viscosity-increasing agent or a surfactant have been proposed for use with administration by oral route or per rectum (Japanese patent application laid-open (kokai) SHO 61-501633).
However, since dispersions are prepared by diluting with water or with an aqueous medium, they easily putrefy due to propagation of microorganisms such as molds and bacteria, and therefore, the addition of preservatives is needed. In order to inhibit the growth of microorganisms such as molds and bacteria, it is required to add preservatives in such amounts that the concentration thereof exceeds a certain threshold value. When contract agents of ferromagnetic preparations are used, relatively large amounts of dose, ranging from 600 to 1,000 ml, must be administered, and therefore, a problem arises in that the total uptake of preservatives can exceed the amount permitted in one day.
In dispersions, most ferromagnetic particles exist as solids suspended therein, and a part of ferromagnetic particles exists in a dissolved state. Generally speaking, a solid state is more stable than a solution state, and therefore, ferromagnetic particles in dispersions are considered disadvantageous compared to those in a solid state with regard to stability.
Moreover, dispersions have the drawback that a large space is required for the storage and transportation of the dispersion preparations. In view of this, granular preparations which are capable of being prepared into a dispersion upon clinical use are desirable compared to preparations supplied, transported and stored in dispersions.
In an attempt to overcome the above drawbacks, granular preparations containing ferromagnetic particles and viscosity-increasing agents have recently been developed (EP 0409351-A1).
However, in order to prepare a dispersion of a granular preparation in water or in an aqueous medium, a stirring operation from 15 seconds to 60 minutes, preferably 2 to 10 minutes, is needed, which is considerably laborious and ti
REFERENCES:
patent: 4719098 (1988-01-01), Weinmann et al.
patent: 5393525 (1995-02-01), Gundersen
Matsumura Manabu
Nakagami Hiroaki
Daiichi Pharmaceutical Co. Ltd.
Jones Dameron L.
Kight John
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