Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1992-09-17
1994-07-12
Hollinden, Gary E.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
424 5, 424646, 424648, 436173, 436806, 423633, 1286534, 514 8, 514 54, 514 57, 514 60, A61B 5055, A61K 3710, A61K 31715
Patent
active
053286812
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to a composition containing ultrafine particles of a magnetic metal oxide, which is useful in the fields of medicine and diagnostic drugs, especially as an MRI contrast agent.
BACKGROUND ART
A composition comprising magnetic metal oxide ultrafine particles, for example, so-called magnetic fluid, has various uses, and there can be mentioned, as one field thereof, a use as a base for diagnostic drugs.
However, in order to safely and efficaciously administer to living organisms metal oxide fine particles of macromolecular size, various factors must be considered. Known preparations have various drawbacks, particularly problems are recognized in the point of biocompatibility, and various proposals are made for improvement. For example, Japanese Tokuhyosho 500196/1989 (PCT/WO88/00060) discloses dextran-coated superparamagnetic fluid dispersed in a polycarboxylic acid buffer. For use of these magnetic fluid preparations in the medical field, some points including toxicity should still be improved.
In the application of magnetic fluid to medicine and diagnostic drugs, particularly as a result of research on the aspect of its toxicity, the present inventors found that magnetic fluid as a foreign substance within living bodies has a bad influence on living bodies, for example, it aggregates platelets which are an important constituent of blood, and this is a cause of toxicity of magnetic fluid.
Thus, the present inventors intensely studied aiming to develop a magnetic fluid which is free of side effects such as platelet aggregation, is excellent in safety to living bodies, and, when intravascularly administered, does not have a bad influence on living bodies. As a result, we have found that when an organic monocarboxylic acid, e.g. lactic acid is compounded into an aqueous sol of a complex of magnetic metal oxide ultrafine particles with a polysaccharide, a polysaccharide derivative and/or a protein, the property of the aqueous sol to aggregate platelets can remarkably be reduced without substantial change in the intrinsic properties of the aqueous sol such as magnetic properties, metabolic properties and tissue specificity, and completed this invention.
DISCLOSURE OF INVENTION
Thus, this invention provides a magnetic metal oxide ultrafine particles-containing composition which comprises an aqueous sol of a complex of magnetic metal oxide ultrafine particles with a polysaccharide, a polysaccharide derivative and/or a protein; and an organic monocarboxylic acid.
The magnetic metal oxide ultrafine particles-containing composition provided by this invention has only weak toxicity; hardly shows any blood pressure lowering effect, which is different from the case of usual magnetic fluids, even when directly administered into blood vessels of animals; and moreover, has only a very small platelet aggregating action and therefore, is excellent in safety as a drug, and can, for example, be used as a MRI contrast agent, a hyperthermic agent or a carrier for drug delivery.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a MR image of the liver site of a Wistar strain rat into whose liver Novikoff tumor was implanted. In FIG. 1, (1A) and (1B) are MR images before administration of the complex sol preparation of this invention prepared in the later-described Example 10, and (1C) and (1D) are MR images at 60 minutes after administration of the preparation. Although the tumor portion cannot be recognized at all in (1A) and (1B), the shape and size of the tumor part can clearly be recognized in (C) and (D).
FIG. 2 (A) and (B) are photomicrographs of the lungs of dd-strain mice to which the complex aqueous sol preparation prepared in the later-described Comparative example 1 and Example 2-3 were administered, respectively. Although marked emboli are observed in the lung in Photograph (2A) (Comparative example 1), no embolus is observed in the lung in photograph (2B) (Example 2-3).
DETAILED DESCRIPTION OF THE INVENTION
The composition of this invention is described in more detail below.
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REFERENCES:
patent: 4663166 (1987-05-01), Veech
patent: 4795698 (1989-01-01), Owen et al.
patent: 5102652 (1992-04-01), Groman et al.
patent: 5160726 (1992-11-01), Josephson et al.
Hasegawa Masakatsu
Hirose Kimio
Hokukoku Shusaburo
Ito Yoshio
Kito Kyoji
Hollinden Gary E.
Meito Sangyo Kabushiki Kaisha
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