Intravascularly-administrable, magnetically-localizable biodegradable carrier

• US 4,247,406 A
• Filed: 04/23/1979
• Issued: 01/27/1981
• Est. Priority Date: 04/23/1979
• Status: Expired due to Term

• Current Assignee: Andrew E. Senyei, Kenneth J. Widder
• Original Assignee: Andrew E. Senyei, Kenneth J. Widder
• Inventors: Senyei, Andrew E., Widder, Kenneth J.
• Primary Examiner(s): Edmundson, F. C.
• Application Number:
  US06/032,399
• Time in Patent Office: 645 Days
• Field of Search: 252/62.53, 252/62.54, 424/1, 424/36
• US Class Current: 424/484
• 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 51/1255 Granulates, agglomerates, microspheres
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: G01N 2333/765 Serum albumin, e.g. HSA
• 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: G01N 33/5434 using magnetic particle immunoreagent carriers which constitute new materials per se

Abstract

The intravascularly-administrable, magnetically localizable biodegradable carrier comprises microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein. The microspheres can be used for intraarterial administration and capillary level localization and/or release of therapeutic and diagnostic agents, thereby obtaining much more precise targeting of the agents than has heretofore been possible.

Claims

1. An intravascularly-administrable, magnetically-localizable biodegradable carrier, comprising microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein, said microspheres having an average size of less than 1.5 microns and said magnetic particles having an average size of not over 1,000 Angstroms, said microspheres containing from 5 to 350 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, at least 90% of said microspheres being immobilized by a magnetic induction of 8,000 gauss when an aqueous suspension of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeter internal diameter but not over 10% of said microspheres being immobilized by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied by a bipolar magnet with its poles equidistant from the centerline of said tube, said 8,000 gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for at least 1.0 centimeter in the direction of flow.

2. The carrier of claim 1 in which said magnetic particles are concentrated in the peripheral portions of said microspheres.

3. The carrier of claim 1 in which said microspheres contain from 10 to 150 parts by weight of said magnetic material per 100 parts of said amino acid polymer.

4. The carrier of claim 3 in which said magnetic material is Fe₃ O₄ and said amino acid polymer is albumin.

5. An intravascularly-administrable, magnetically-localizable biodegradable carrier, comprising microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein, said microspheres having an average size of less than 1.2 microns and said magnetic particles having an average size of not over 300 Angstroms, said microspheres containing from 10 to 150 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, at least 95% of said microspheres being immobilized by a magnetic induction of 8,000 gauss when an aqueous suspension of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeters internal diameter but not over 5% of said microspheres being immobilized by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied with a bipolar magnet with its poles equidistant from the centerline of said tube, said 8,000 gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for at least 1.0 centimeter in the direction of flow.

6. The carrier of claim 5 in which said magnetic particles are concentrated in the peripheral portions of said microspheres.

7. The carrier of claim 5 in which said magnetic material is Fe₃ O₄ and said amino acid polymer is albumin.

8. An intravascularly-administrable, magnetically-localizable biodegradable carrier, comprising microspheres formed from albumin with particles of Fe₃ O₄ embedded therein, said microspheres having an average size of less than 1.2 microns and said magnetic particles having an average size of not over 300 Angstroms, said microspheres containing from 10 to 150 parts by weight of said Fe₃ O₄ particles per 100 parts of said albumin, at least 95% of said microspheres being immobilized by a magnetic induction of 8,000 gauss when an aqueous suspension of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeters internal diameter but not over 5% of said microspheres being immobilized by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied with a bipolar magnet with its poles equidistant from the centerline of said tube, said 8,000 gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for at least 1.0 centimeter in the direction of flow.

9. The carrier of claim 8 in which said Fe₃ O₄ particles are concentrated in the peripheral portions of said microspheres.

10. An intravascularly-administrable, magnetically-localizable biodegradable carrier, comprising microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein, said microspheres having an average size of less than 1.5 microns and said magnetic particles having an average size of not over 1,000 Angstroms, said microspheres containing from 5 to 350 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, at least 90% of said microspheres being immobilized by a magnetic induction of 8,000 gauss when an aqueous suspension of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeter internal diameter but not over 10% of said microspheres being immobilized by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied by a bipolar magnet having pole faces of 12.7 millimeters in width with said pole faces equidistant from the centerline of said tube, said 8,000 gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for substantially 12.7 millimeters in the direction of flow.

11. An intravascularly-administrable, magnetically-localizable biodegradable carrier, comprising microspheres formed from an amino acid polymer matrix with magnetic particles embedded therein, said microspheres having an average size of less than 1.2 microns and said magnetic particles having an average size of not over 300 Angstroms, said microspheres containing from 10 to 150 parts by weight of said magnetic particles per 100 parts of said amino acid polymer, at least 95% of said microspheres being immobilized by a magnetic induction of 8,000 gauss when an aqueous suspension of said microspheres is pumped at a rate of 0.05 centimeters per second through a conduit of 0.168 centimeters internal diameter but not over 5% of said microspheres being immobilized by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied by a bipolar magnet having pole faces of 1.27 centimeters in width with said pole faces equidistant from the centerline of said tube, said 8,000 gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for substantially 1.27 centimeters in the direction of flow.

12. An intravascularly-administrable, magnetically-localizable biodegradable carrier, comprising microspheres formed from albumin with particles of Fe₃ O₄ embedded therein, said microspheres having an average size of less than 1.2 microns and said magnetic particles having an average size of not over 300 Angstroms, said microspheres containing from 10 to 150 parts by weight of said Fe₃ O₄ particles per 100 parts of said albumin, at least 95% of said microspheres being immobilized by a magnetic induction of 8,000 gauss when an aqueous suspension of said microspheres is pumped at a rate of 0.05 centimeters per second over 5% of said microspheres being immobilized by said magnetic induction when pumped through said conduit at a flow rate of 10 centimeters per second, said magnetic induction being applied by a bipolar magnet having pole faces of 1.27 centimeters in width with said pole faces equidistant from the centerline of said tube, said 8,000 gauss being referenced to a plane intersecting said tube at right angles to the direction of flow and extending for substantially 1.27 centimeters in the direction of flow.