Devices for controlling magnetic nanoparticles to treat fluid obstructions

• US 8,715,150 B2
• Filed: 11/02/2010
• Issued: 05/06/2014
• Est. Priority Date: 11/02/2009
• Status: Active Grant

• Current Assignee: Pulse Therapeutics, Inc. (Euphrates Vascular, Inc.)
• Original Assignee: Pulse Therapeutics, Inc. (Euphrates Vascular, Inc.)
• Inventors: Creighton, Francis M.
• Primary Examiner(s): Matthews, Christine
• Assistant Examiner(s): Reddy, Sunita
• Application Number:
  US13/505,447
• Publication Number:
  US 20120310034A1
• Time in Patent Office: 1,281 Days
• Field of Search: 977/700, 977/737, 977/745, 977/773, 977/786, 977/833, 977/838, 977/839, 977900-902, 977904-906, 977/908, 977/915, 977/959, 977/963, 600/407, 600/427, 600/9, 600/12, 600/13, 600/114, 600/117, 600/118, 600/424, 128897-898, 335/300, 607/1, 424/489, 606/159
• US Class Current: 600/12
• CPC Class Codes: A61B 17/22 Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for dilators A61M29/00
• CPC Class Codes: A61B 17/22012 in direct contact with, or very close to, the obstruction or concrement for removing obstructions in blood vessels by laser A61B18/245
• CPC Class Codes: A61B 2017/00876 magnetic
• CPC Class Codes: A61B 2017/22084 stone- or thrombus-dissolving
• CPC Class Codes: A61B 2017/22094 for crossing total occlusions, i.e. piercing
• CPC Class Codes: A61B 2034/733 arranged only on one side of the patient, e.g. under a table
• CPC Class Codes: A61B 34/73 Manipulators for magnetic surgery
• CPC Class Codes: A61K 38/482 Serine endopeptidases (3.4.21)
• CPC Class Codes: A61K 38/484 Plasmin (3.4.21.7)
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 47/6941 the form being a granulate or an agglomerate
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61N 2/004 specially adapted for a specific therapy
• CPC Class Codes: A61N 2/02 using magnetic fields produced by coils, including single turn loops or electromagnets A61N2/12 takes precedence
• CPC Class Codes: A61N 2/06 using magnetic fields produced by permanent magnets A61N2/12 takes precedence
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C12Y 304/21007 : Plasmin (3.4.21.7), i.e. fibrinolysin
• CPC Class Codes: C12Y 304/21068 : Tissue plasminogen activator (3.4.21.68), i.e. tPA
• CPC Class Codes: H01F 7/0273 : Magnetic circuits with PM for magnetic field generation
• CPC Class Codes: Y10S 977/811 : Of specified metal oxide composition, e.g. conducting or semiconducting compositions such as ITO, ZnOx
• CPC Class Codes: Y10S 977/905 : Specially adapted for travel through blood circulatory system
• CPC Class Codes: Y10S 977/909 : Obstruction removal

Abstract

The present invention relates to a system for the physical manipulation of free magnetic rotors in a circulatory system using a remotely placed magnetic field-generating stator. In one aspect, the invention relates to the control of magnetic particles in a fluid medium using permanent magnet-based or electromagnetic field-generating stator sources. Such a system can be useful for increasing the diffusion of therapeutic agents in a fluid medium, such as a human circulatory system, which can result in substantial clearance of fluid obstructions, such as vascular occlusions, in a circulatory system resulting in increased blood flow. Examples of vascular occlusions targeted by the system include, but are not limited to, atherosclerotic plaques, including fibrous caps, fatty buildup, coronary occlusions, arterial stenosis, restenosis, vein thrombi, arterial thrombi, cerebral thrombi, embolisms, hemorrhages, other blood clots, and very small vessels.

Claims

1. A system for treating a fluid obstruction through external magnetomotive manipulation of magnetic nanoparticles introduced within vasculature of a subject, the system comprising:

a least one motor;

a magnet having a magnetic field and a directed magnetic gradient that are configured to provide external magnetomotive manipulation of magnetic nanoparticles introduced within vasculature of a subject; and

a controller that is configured to cause the at least one motor (a) to control a position, rotation plane and rotation frequency of the magnetic field of the magnet to create a potion, rotation plane and rotation frequency of the magnetic field of the magnet to create a rotating, time-varying magnetic field and (b) to control magnetic components of the magnetic gradient of the magnet,

wherein the controller is configured to position and rotate the magnetic field and direct the magnetic gradient in a manner sufficient to cause magnetic nanoparticles introduced within vasculature to agglomerate into a plurality of magnetic nanoparticle rods,

wherein the time-varying magnetic field and the directed magnetic gradient are configured to cause the magnetic nanoparticle rods to individually walk in an end over end motion to collectively generate a circulating fluid motion within a blood vessel proximal to a fluid obstruction, and

wherein the circulating fluid motion facilitates contact of a therapeutic agent introduced within the blood vessel with the fluid obstruction.

2. The system of claim 1, wherein the magnetic nanoparticle rods are configured to travel through the blood vessel by repeatedly:

a) walking end over end along the blood vessel away from the magnetic field in response to the rotation of the magnetic nanoparticle rods and the directed magnetic gradient; and

b) flowing back through fluid in the blood vessel towards the magnetic field in response to the rotation of the magnetic nanoparticle rods and the directed magnetic gradient.

3. The system of claim 1, wherein the circulating fluid motion facilitates contact of a therapeutic agent with the fluid obstruction by enhancing diffusion of the therapeutic agent to a region of the blood vessel proximal to the fluid obstruction and by refreshing contact of the fluid obstruction with the therapeutic agent, thereby providing more effective interaction of the therapeutic agent with the fluid obstruction.

4. The system of claim 1, wherein the therapeutic agent comprises a thrombolytic agent.

5. The system of claim 1, wherein the magnet is a permanent magnet.

6. The system of claim 1, further comprising the plurality of magnetic nanoparticles, and wherein the magnetic nanoparticles comprise a plurality of coated magnetic nanoparticles having a diameter of between about 15 nm and 150 nm adapted for introduction into the vasculature.

7. The system of claim 6, wherein the magnetic nanoparticles comprise magnetite nanoparticles having a diameter of between about 20 nm and 60 nm.

8. The system of claim 6, wherein the therapeutic agent is attached to the plurality of magnetic nanoparticles, and wherein the therapeutic agent is tissue plasminogen activator (tPA).

9. The system of claim 1, wherein the nanoparticle rods have a length between 0.1 and 2 millimeters when exposed to a rotating time-varying magnetic field magnitude of between 0.01 Tesla and 0.1 Tesla and a magnetic gradient strength of between 0.01 Tesla/meter and 5 Tesla/meter.

10. The system of claim 1, wherein the rotation frequency is between 1 Hz and 30 Hz, wherein the magnitude of the magnetic field of the magnet is between 0.01 Tesla and 0.1 Tesla, wherein the strength of the magnetic gradient is between 0.01 Tesla/meter and 5 Tesla/meter, and wherein the controller is adapted to adjust the rotation frequency and/or the strength of the magnetic gradient.

11. The system of claim 1, wherein the magnet is an electromagnet.

12. The system of claim 1, wherein the at least one motor is configured to cause rotation of at least a first gear.

13. The system of claim 1, wherein the system is suspended by a suspension arm that is coupled to an arm positioner of a portable base by a suspension arm attachment joint.

14. The system of claim 13, wherein the suspension arm attachment joint is configured to allow rotation of the system about an end of the arm positioner coupled to the suspension arm attachment joint.

15. The system of claim 1, wherein the system comprises two motors, with a first motor adapted to rotate around a first axis to cause rotation of the magnet and a second motor adapted to rotate around a second axis to set an orientation of the rotation plane.

16. The system of claim 1,

wherein the controller comprises a computer control panel having a user interface adapted to allow an operator to manipulate the position, rotation plane and rotation frequency of the magnetic field of the magnet, and

wherein the controller is configured to perform image processing to identify the location, shape, thickness and density of the fluid obstruction and automatically manipulates the at least one motor to control a position, rotation plane and rotation frequency of the magnetic field of the magnet based on the image processing.

17. The system of claim 1, wherein the fluid obstruction is a cerebral thrombus.

18. The system of claim 1, wherein the fluid obstruction is a coronary occlusion.

19. The system of claim 1, wherein the fluid obstruction is an embolism.

20. The system of claim 1, wherein the fluid obstruction is a blood clot.

21. A system for treating a fluid obstruction through external magnetomotive manipulation of magnetic nanoparticles introduced within vasculature of a subject, the system comprising:

a permanent magnet coupled to mounting flanges on opposite sides of the permanent magnet;

a first drive motor configured to rotate the permanent magnet around a first axis;

a second drive motor configured to rotate the permanent magnet around a second axis to set an orientation of a rotation plane of the permanent magnet such that the permanent magnet is configured to rotate in such a manner to provide a rotating, time-varying magnetic field and a directed magnetic gradient that allows for external magnetomotive manipulation of magnetic nanoparticles introduced within vasculature of a subject; and

a controller configured to cause the first and second drive motors (a) to control a position, rotation plane and rotation frequency of the magnetic field of the permanent magnet and (b) to control magnetic components of the magnetic gradient of the permanent magnet,

wherein the controller is configured to position and rotate the magnetic field and direct the magnetic gradient in a manner sufficient to cause magnetic nanoparticles introduced within vasculature to agglomerate into a plurality of magnetic nanoparticle structures,

wherein the magnetic field and the magnetic gradient are configured to cause the magnetic nanoparticle structures to individually walk in an end over end motion to collectively generate a circulating fluid motion within a blood vessel proximal to a fluid obstruction, and

wherein the circulating fluid motion facilitates contact of a therapeutic agent introduced within the blood vessel with the fluid obstruction.

22. The system of claim 21, wherein the permanent magnet is a cylindrical magnet.

23. The system of claim 21, wherein the system is suspended by a suspension arm that is coupled to an arm positioner of a portable base by a suspension arm attachment joint.

24. The system of claim 23, wherein the suspension arm attachment joint is configured to allow rotation of the system about an end of the arm positioner coupled to the suspension arm attachment joint.