Nanocrystalline magnetic iron oxide particles-method for preparation and use in medical diagnostics and therapy

• US 5,427,767 A
• Filed: 05/13/1992
• Issued: 06/27/1995
• Est. Priority Date: 05/28/1991
• Status: Expired due to Term

• Current Assignee: Institut fur Diagnostikforschung GmbH
• Original Assignee: Institut fur Diagnostikforschung GmbH
• Inventors: Lawaczeck, Rudiger, Kresse, Mayk, Pfefferer, Detlef
• Primary Examiner(s): Hollinden, Gary E.
• Application Number:
  US07/882,130
• Time in Patent Office: 1,140 Days
• Field of Search: 424/9, 436/173, 436/806, 514/54, 514/56, 128/653.4
• US Class Current: 424/9.32
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 49/1839 the small organic molecule being a lipid, a fatty acid having 8 or more carbon atoms in the main chain, or a phospholipid
• CPC Class Codes: A61K 49/1863 the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
• CPC Class Codes: A61K 49/1866 the nanoparticle having a (super)(para)magnetic core coated or functionalised with a peptide, e.g. protein, polyamino acid
• CPC Class Codes: A61K 49/189 Host-guest complexes, e.g. cyclodextrins
• CPC Class Codes: A61K 51/1251 micro- or nanospheres, micro- or nanobeads, micro- or nanocapsules
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 2400/40 Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides
• CPC Class Codes: G01N 2446/20 the magnetic material being present in the particle core
• CPC Class Codes: G01N 2446/30 the magnetic material being dispersed in the polymer composition before their conversion into particulate form
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The invention relates to nanocrystalline magnetic particles consisting of gnetic iron oxide core of Fe₃ O₄, gamma-Fe₂ O₃ or mixtures thereof and an envelope chemisorbed to said core, the method for preparation of these particles as well as the use thereof in medical diagnostics and/or therapy. The magnetic particles, according to the invention, are characterized by composition of the coating material of natural or synthetic glycosaminoglycans and/or their derivatives with molecular weights of 500 Da to 250,000 Da, if necessary, covalently cross-linked with appropriate cross-linking agents and/or modified by specific additives.

Claims

1. Nanocrystalline magnetic particles consisting of a magnetic iron oxide core of FE₃ O₄, gamma-Fe₂ O₃ or mixtures thereof and a chemisorbed coating on this core, wherein composition of the coating material of natural or synthetic glycosaminoglycans and/or derivatives thereof with molecular weights of 500 Da to 250,000 Da combined, optionally covalently cross-linked by appropriate cross-linking agents and/or modified by specific additives.

2. Magnetic particles according to claim 1 wherein said particles have core diameters smaller than the dimensions of the magnetic singular domains.

3. Magnetic particles according to claim 1 wherein said particles optionally are available with the common pharmaceutical adjuvants for injectable solutions and/or enteral agents as stable aqueous colloid dispersive solutions which are 0.2 μ

m filterable and optionally can be heat sterilized.

4. Magnetic particles according to claim 1 wherein the natural or synthetic glycosaminoglycans are chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and synthetic analogues thereof or other heparinoids.

5. Magnetic particles according to claim 1 wherein the coating material after preparation of enveloped magnetic iron oxide particles, is additionally cross-linked by cross-linkers common in biochemistry and chemistry of natural products.

8. Magnetic particles according to claim 1 wherein the glycosaminoglycan is chondroitin sulfate, keratin sulfate, dermatan sulfate, hyaluronic acid, heparan sulfate or synthetic analog thereof.

9. Magnetic particles according to claim 1 wherein the glycosaminoglycan is chondroitin sulfate, keratin sulfate, dermatan sulfate, hyaluronic acid, or synthetic analog thereof.

10. Magnetic particles according to claim 1 wherein the glycosaminoglycan is chondroitin sulfate, keratin sulfate, dermatan sulfate or hyaluronic acid.

11. Magnetic particles according to claim 1 wherein the glycosaminoglycan is chondroitin sulfate or dermatan sulfate.

6. Diagnostic and/or therapeutic agents comprising optionally isotope doped iron oxide cores of FE₃ O₄, gamma-Fe₂ O₃ or their mixtures, which are surrounded by a biodegradable coating of natural or synthetic glycosaminoglycans and/or derivatives thereof with molecular weights between 500-250,000 Da, with the coating molecules possibly being cross-linked by cross-linking agents and modified by surface-active substances, targetable structure substances and lower molecular weight residues.

7. Diagnostic and/or therapeutic agents according to claim 6 wherein the natural or synthetic glycosaminoglycans are chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and their synthetic analogues which are cross-linked by bifunctional cross-linking agents common in biochemistry and chemistry of natural products and/or are cross-linked with mono-, di-, tri-, and oligoamines, synthetic and biological oligopeptides, reduced or oxidized glutathione.