Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1995-09-12
1999-06-29
Hollinden, Gary E.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
424646, 424648, 514 54, A61B 5055
Patent
active
059165391
DESCRIPTION:
BRIEF SUMMARY
The invention relates to superparamagnetic particles which have chemically bound substances on their surface, optionally possess further binding sites for coupling tissue-specific binding substances, diagnostic or pharmacologically acting substances and to new related compounds and to the use of these particles and compounds in medicine for destroying tumours, increasing immunity and diagnosing conditions.
Magnetic particles have been described in a plurality of publications and patents, in particular for magnetic separation techniques and for use as contrast agents in NMR diagnosis.
In the sixties, attempts were made to use ferromagnetic particles as contrast agents for X-ray diagnosis and for magnetically controlled drug targeting, for example, Meyers, P. H. et al. J. Am. J. Roentgenol. Radium Ther. Nucl. Med., 90,1068.1963; Frei, F. H. et al. J. Appl. Phys., 39,999,1968; Nakamura et al. J. Appl. Phys., 42,1320,1971. The irreversible aggregation of the magnetic particles under the influence of a magnetic field proved to be a problem during in vivo application. The same applies to DE-A-3590398, U.S. Pat. No. 4,675,173, U.S. Pat. No. 4,615,879, WO 84/02643, GB-A-8408127 and WO 84/04330. Ferromagnetic particles with Weiss' domains of the order of a few hundred to a few thousand Angstrom units provided with a polymer coating to enable substances having a binding affinity for tissue to be coupled are proposed here.
Ferromagnetic particles of the suggested size have such great magnetic moments that the particles agglomerate to form greater aggregates even when they are provided with a polymer coating. The particles exist in aggregate form even during the coating process. Such ferromagnetic particles would sediment in the body during parenteral administration and the toxic side effects would be great.
Similar drawbacks also apply to the dispersions of ferromagnetic particles used in DE-A-3443251 and DE-A-3443252, where the magnetic interactions between the particles lead to aggregation and sedimentation. The irreversible sedimentation of the magnetic particles takes place very rapidly, particularly under the influence of magnetic fields. If there are inhomogeneities in the magnetic field, the magnetic particles invariably concentrate at the points with high field strengths. These drawbacks occur in particular during NMR diagnosis and during magnetic drug targeting, and very great irreversible aggregates of particles can be formed, giving rise to a great risk of embolism.
Even greater ferromagnetic particles are described in U.S. Pat. No. 3,933,997, U.S. Pat. No. 3,652,761, Nature 270,259,1977, J. Allergy Clin. Immunol. 61,23,1978, U.S. Pat. No. 4,177,253, Clin. Chem., 26,730,1980, Clin. Chem., 26,1281,1980, U.S. Pat. No. 3,970,518, U.S. Pat. No. 4,230,685, U.S. Pat. No. 4,267,234, U.S. Pat. No. 4,152,210, U.S. Pat. No. 4,343,901. These magnetic particles with diameters between 10 and 160 .mu.m can be separated even with weak magnetic fields but have the drawback that they sediment very rapidly, possess a small specific surface area for the binding of pharmacologically active substances, agglomerate irreversibly in the magnetic field and are too large for drug targeting owing to the risk of embolism.
The irreversible agglomeration of the magnetic particles in the magnetic field can be avoided by using superparamagnetic particles. Superparamagnetic particles have no remanence, i.e. they can be moved and concentrated reversibly in a magnetic gradient field. These superparamagnetic particles include, for example, iron oxides having a particle diameter smaller than 0.02 .mu.m.
To prevent these superparamagnetic particles from sedimenting in aqueous dispersions, stabilizer substances which attach themselves to the particle surfaces by adsorption are added.
Such particles are described in U.S. Pat. No. 3,215,572, U.S. Pat. No. 3,531,413, U.S. Pat. No. 3,917,538, WO 85/02772, U.S. Pat. No. 4,101,435 and U.S. Pat. No. 4,452,773, SE-A-8307060-7.
The adsorption-stabilized magnetic particles are not stable under physiologi
REFERENCES:
patent: 3917538 (1975-11-01), Bass
patent: 3933997 (1976-01-01), Hersh
patent: 3970518 (1976-07-01), Giaever
patent: 4101435 (1978-07-01), Hasegawa
patent: 4152210 (1979-05-01), Robinson
patent: 4177253 (1979-12-01), Davies
patent: 4230685 (1980-10-01), Senyei
patent: 4267234 (1981-05-01), Rembaum
patent: 4343901 (1982-08-01), De Filippi
patent: 4452773 (1984-06-01), Molday
patent: 4554088 (1985-11-01), Whitehead
patent: 4615879 (1986-10-01), Runge
patent: 4675173 (1987-06-01), Widder
patent: 4767611 (1988-08-01), Gordon
patent: 4863715 (1989-09-01), Jacobsen et al.
patent: 4925678 (1990-05-01), Ranney
patent: 5069216 (1991-12-01), Groman et al.
patent: 5160725 (1992-11-01), Pilgrimm
patent: 5225282 (1993-07-01), Chagnon et al.
patent: 5314679 (1994-05-01), Lewis et al.
patent: 5328681 (1994-07-01), Kito et al.
patent: 5349957 (1994-09-01), Yudelson
patent: 5358702 (1994-10-01), Unger
Meyers, P.H. et al., J.Am. J. Roentgenol, Radium Ther. Nucl. Med., 90,1068, 1963.
Frei, F.H. et al., J Appl. Phys., 39,999, 1968.
Nakamura et al., J. Appl. Phys., 42,1320, 1971.
Nature 270,259, 1977.
J. Allergy Clin. Immunol. 61,23, 1978.
Clin. Chem. 26,730, 1980.
Clin. Chem., 26,281, 1980.
Ito, R., et al., Int. J. Pharm., 61,109 1990.
Roch et al, Magma vol. 1, No. 2, 1993, pp. 83-88.
Hollinden Gary E.
Silica Gel Ges. m.b.H.
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