Biodegradable magnetic microcluster comprising non-magnetic metal or metal oxide particles coated with a functionalized polymer

• US 5,225,282 A
• Filed: 12/13/1991
• Issued: 07/06/1993
• Est. Priority Date: 12/13/1991
• Status: Expired due to Fees

• Current Assignee: Molecular Bioquest, Inc.
• Original Assignee: Molecular Bioquest, Inc.
• Inventors: Ferris, John R., Chagnon, Mark S., Carter, Michelle J., Hamilton, Tracy J., Fiore, Barry L.
• Primary Examiner(s): Thibodeau, Paul J.
• Assistant Examiner(s): Resan, Stevan A.
• Application Number:
  US07/806,478
• Time in Patent Office: 571 Days
• Field of Search: 428/407, 252/62.54, 252/62.58, 252/62.64, 264/126, 264/DIG. 58, 436/526, 436/173
• US Class Current: 428/407
• 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 47/6941 the form being a granulate or an agglomerate
• CPC Class Codes: A61K 49/1821 coated or functionalised microparticles or nanoparticles
• CPC Class Codes: A61K 49/183 having a (super)(para)magnetic core coated or functionalised with an inorganic material or being composed of an inorganic material entrapping the MRI-active nucleus, e.g. silica core doped with a MRI-active nucleus
• CPC Class Codes: A61K 49/1833 having a (super)(para)magnetic core coated or functionalised with a small organic molecule oligomeric, polymeric, dendrimeric A61K49/1851
• CPC Class Codes: A61K 49/1854 the organic macromolecular compound being obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly(meth)acrylate, polyacrylamide, polyvinylpyrrolidone, polyvinylalcohol
• CPC Class Codes: A61K 49/1887 Agglomerates, clusters, i.e. more than one (super)(para)magnetic microparticle or nanoparticle are aggregated or entrapped in the same maxtrix
• CPC Class Codes: Y10S 428/90 Magnetic feature
• CPC Class Codes: Y10T 428/256 Heavy metal or aluminum or compound thereof
• CPC Class Codes: Y10T 428/26 Web or sheet containing structurally defined element or component, the element or component having a specified physical dimension
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Subdomain metal or metal oxide particles covalently coupled to chemically reactive organic moieties and subsequently reacted together to form biodegradable magnetic microclusters are disclosed. The magnetic microcluster can be used as contrast agents in NMR imaging for the production of images suitable for use in diagnosis, for in vivo delivery and targeting of drugs, as in vivo, biodegradable agents for the sequestering of free metal ions in the treatment of metal driven disease.

Claims

1. A biodegradable magnetic microcluster comprising a cluster of non-magnetic metal or metal oxide particles having a crystallite size of 70 Angstroms or less which are coated with a functionalized polymer wherein the magnetic microcluster is about 100 Angstroms to 2 microns in size and is formed by chemical interaction between the functional groups of the polymer.

2. The biodegradable magnetic cluster of claim 1 wherein the polymer is an organometallic polymer.

3. The biodegradable magnetic microcluster of claim 1 having a cluster size of from about 100 Angstroms.

4. The biodegradable magnetic microcluster of claim 1 wherein the metal or metal oxide particles are comprised of a material selected from the group consisting of:

iron, magnesium, manganese, cobalt, nickel, zinc, copper, iron alloys, cobalt ferrite, samarium cobalt, barium ferrite, aluminum-nickel-cobalt, magnetite, hematite and chromium dioxide.

5. The biodegradable magnetic microcluster of claim 1 wherein the cluster is superparamagnetic and the individual particles are non-magnetic.

6. The biodegradable magnetic microcluster of claim 1 wherein the crystallite particle size is from about 10 Angstroms to about 70 Angstroms.

7. The biodegradable magnetic microclusters of claim 6 wherein the particles have a surface area of from about 25 to 1000 square meters per gram.

8. The biodegradable magnetic microcluster of claim 2 wherein the functionalized organometallic polymer coatings are formed by crosslinking between monomers which comprise coordinate complexes of a transition or post-transition metal and a functionalized organic ligand.

9. The biodegradable magnetic microcluster of claim 8 wherein the functionalized organometallic polymer coating is adsorbed onto or covalently bound to the crystallites and the functional groups are reacted together via covalent crosslinking to form magnetizable microclusters.

10. The biodegradable magnetic microcluster of claim 1 wherein the functional group is selected from the groups consisting of an amine, carboxyl, cyanate, phosphate, sulfate, thiol, hydroxyl, and functionalized ligand.

11. The biodegradable magnetic microcluster of claim 8 wherein the organometallic monomer is selected from the group consisting of:

amino-hexyl-titanium triisopropoxide, amino-propyl-titanium triisopropoxide and carboxy-hexyl-titanium triisopropoxide.

12. A biodegradable superparamagnetic microcluster comprising a cluster of non-magnetic metal or metal oxide particles having a crystalline size of about 70 Angstroms or less, which are coated with amino-hexyl-titanium triisopropoxide, wherein the microcluster is formed by covalent bonding or complexation of the amino-functional groups to a cluster size from about 100 Angstroms to 2 microns.