Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1993-02-11
1995-06-13
Knode, Marian C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
514 54, 514 59, 514 60, 424 9322, 1286534, 128654, 436173, C08B 3702, A61K 3172, A61K 4900, A61B 5055
Patent
active
054244196
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel oxidized complex comprising a water-soluble carboxypolysaccharide and magnetic iron oxide, which is particularly useful in biological and medical fields such as contrast medium for magnetic resonance imaging, exothermic medium for hyperthermia, contrast medium for X-ray imaging and the like.
BACKGROUND ART
Ultrafine particles of magnetic iron oxide having colloidal sizes have superparamagnetism, and an aqueous sol thereof as a magnetic fluid has recently drawn attention as a contrast medium for use in magnetic resonance imaging. The aqueous sol comprising magnetic iron oxide ultrafine particles alone, however, has very low stability when a salt has been added thereto or when subjected to thermal sterilization or with time and has very high acute toxicity when administered intravenously; hence, the aqueous sol is unusable for medical treatment and efforts have been made to solve these problems.
As a means for improving the above stability and safety, it was proposed to form a complex between a polysaccharide or the like and ultrafine particles of magnetic iron oxide. For example, Japanese Patent Publication No. 13521/1984 (U.S. Pat. No. 4,101,435) discloses a complex between dextran or a carboxydextran obtained by heat-treating dextran with sodium hydroxide and ultrafine particles of magnetic iron oxide; U.S. Pat. No. 4,452,773 discloses dextran-magnetic iron oxide microspheres; and Japanese Patent Publication No. 500196/1989 (International Publication WO No. 88/00060) discloses a composition of dextran-magnetic iron oxide microspheres similar to the above, for use in in-vivo magnetic resonance imaging for the organs and tissues of animals (reference is made to Comparative Example 1 described later). Of these, a carboxydextran-magnetic iron oxide ultrafine particles complex, in particular, is remarkably improved in various stabilities and acute toxicity. However, it was confirmed that these complexes and microspheres each as an aqueous sol, when administered into blood vessels, incur significant reduction in blood pressure, leading to death in some cases.
Hence, the present inventors made an extensive study. As a result, the present inventors found that an oxidized complex obtained by treating a water-soluble carboxypolysaccharide-magnetic iron oxide ultrafine particles complex with an oxidizing agent such as oxygen gas or the like shows little or no blood pressure-reducing action without substantially affecting the properties possessed by the raw complex, such as magnetic property, metabolic property, tissue specificity and the like, and further can significantly reduce the platelets-aggregating action considered to be connected with blood pressure reduction. The present invention has been completed based on the above finding.
DISCLOSURE OF THE INVENTION
According to the present invention, there is provided an oxidized complex comprising a water-soluble carboxypolysaccharide and magnetic iron oxide, which is characterized by being obtained by oxidizing a complex comprising a water-soluble carboxypolysaccharide and magnetic iron oxide.
The oxidized complex comprising a water-soluble carboxypolysaccharide and magnetic iron oxide, provided by the present invention, when being in the form of an aqueous sol, has very low toxicity and excellent stability, shows little or no blood pressure-reducing action unlike conventional complexes when administered directly into the blood vessels of animals, has low platelets-aggregating action, has excellent safety as drug, and can be suitably used in a medical field as, for example, a contrast medium for nuclear magnetic resonance imaging (hereinafter abbreviated to MRI), a exothermic medium for hyperthermia and a carrier for drug delivery.
Detailed description is made hereinafter on the oxidized complex comprising a water-soluble carboxypolysaccharide and magnetic iron oxide (hereinafter referred to as oxidized complex, in some cases) of the present invention.
The oxidized complex of the present invention can
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Hasegawa Masakatsu
Hirose Kimio
Hokukoku Shusaburo
Ito Yoshio
Kito Kyoji
Knode Marian C.
Meito Sangyo Kabushiki Kaisha
Prats Francisco C.
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