Magnetic-based methods for treating vessel obstructions

• US 8,313,422 B2
• Filed: 05/15/2012
• Issued: 11/20/2012
• 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): Gilbert, Samuel G.
• Assistant Examiner(s): Reddy, Sunita
• Application Number:
  US13/471,908
• Publication Number:
  US 20120232329A1
• Time in Patent Office: 189 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, 128/897, 128/898, 128/899, 335/300, 600/407, 600/427, 600/9, 600/12, 600/13, 600/114, 600/117, 600/118, 600/424, 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

Some embodiments provide a system for external manipulation of magnetic nanoparticles in vasculature using a remotely placed magnetic field-generating stator. In one aspect, the systems and methods relate to the control of magnetic nanoparticles 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.

Claims

1. A method of treating a thrombus within a blood vessel of the brain through external magnetomotive manipulation of magnetic nanoparticles, the method comprising:

introducing a thrombolytic drug within vasculature of a subject, the thrombolytic drug configured to have a therapeutic effect on a thrombus within a blood vessel of the brain;

introducing a plurality of coated magnetic nanoparticles within the vasculature of the subject,

wherein the magnetic nanoparticles have a diameter between about 15 nm and 150 nm;

orienting a permanent magnet external to the blood vessel and having a magnetic field and a directed magnetic gradient to establish a magnetic rotation plane of the permanent magnet;

programming a controller to cause the permanent magnet to be positioned and to rotate in a manner sufficient to cause the magnetic nanoparticles to agglomerate to form a plurality of magnetic nanoparticle rods having a length between 0.1 and 2 millimeters within the vasculature to travel toward the thrombus in an end over end walking motion in response to torque exerted by the rotating magnetic field and to an attractive force of the directed magnetic gradient,

wherein the rotational frequency of the rotating magnetic field is between 1 Hz and 30 Hz,

wherein the rotating magnetic field has a magnitude of between 0.01 Tesla and 0.1 Tesla,

wherein the directed magnetic gradient has a strength of between 0.01 Tesla/meter and 5 Tesla/meter,

wherein the end over end walking motion of each of the magnetic nanoparticle rods generates a circulating fluid motion within the vasculature proximal to the thrombus, and

wherein the circulating fluid motion facilitates contact of the thrombolytic drug with the thrombus by enhancing diffusion of the thrombolytic drug to the region of the blood vessel proximal to the thrombus and by refreshing contact of the thrombus with the thrombolytic drug, thereby providing more effective interaction of the thrombolytic drug with the thrombus.

2. The method of claim 1, wherein the thrombolytic drug is attached to the magnetic nanoparticles prior to introduction.

3. The method of claim 1, wherein the thrombolytic drug is introduced within the vasculature separate from the magnetic nanoparticles.

4. The method of claim 1, wherein the permanent magnet is rotatably coupled to a motor by a movable arm.

5. The method of claim 1, wherein said introducing a thrombolytic drug within vasculature of a subject comprises introducing a reduced dose of the thrombolytic drug than would be introduced if the magnetic nanoparticles were not introduced.

6. The method of claim 1, wherein said step of programming the controller comprises adjusting the rotational frequency of the rotating magnetic field, a plane of the rotating magnetic field with respect to the thrombus, and/or a distance of the rotating magnetic field with respect to the thrombus.

7. The method of claim 1, further comprising adjusting one or more of the position, the rotation plane and the rotation frequency of the magnetic field in response to at least one characteristic of the thrombus.

8. The method of claim 7, wherein the at least one characteristic is selected from the group consisting of:

a location, a shape, a thickness, and a density of the thrombus.

9. The method of claim 7, wherein the at least one characteristic is determined from one or more images of the region of the blood vessel in which the thrombus is located.

10. The method of claim 1, wherein said orienting a permanent magnet having a magnetic field and a directed magnetic gradient to establish a magnetic rotation plane of the permanent magnet is performed based on preoperative images of the blood vessel.

16. The method of claim 1 or 11, wherein the step of programming the controller is performed by a user via a touch screen display or a control button on a handheld device.

11. A method of treating a thrombus within a blood vessel of a subject through external magnetomotive manipulation of magnetic nanoparticles, the method comprising:

introducing a thrombolytic agent within vasculature of a subject, the thrombolytic agent configured to facilitate lysis of a thrombus within a blood vessel;

administering a therapeutically effective amount of magnetic nanoparticles within the vasculature,

wherein the magnetic nanoparticles have a diameter between about 15 nm and 150 nm;

positioning a magnet external to the blood vessel and having a magnetic field and a directed magnetic gradient to establish a magnetic rotation plane of the magnet;

programming a controller to cause the magnet to be positioned and to rotate in a manner sufficient to cause the magnetic nanoparticles to agglomerate to form a plurality of magnetic nanoparticle rods having a length between 0.1 and 2 millimeters within the vasculature and to cause the magnetic nanoparticle rods to travel within the vasculature toward the thrombus within the blood vessel by individually walking end over end in response to the rotating magnetic field and the directed magnetic gradient of the magnet;

wherein the rotational frequency of the rotating magnetic field is between 1 Hz and 30 Hz,

wherein the rotating magnetic field has a magnitude of between 0.01 Tesla and 0.1 Tesla,

wherein the directed magnetic gradient has a strength of between 0.01 Tesla/meter and 5 Tesla/meter; and

adjusting a frequency of the rotating magnetic field, a plane of the rotating magnetic field with respect to the thrombus, and a distance of the rotating magnetic field with respect to the thrombus to cause the magnetic nanoparticle rods to generate a circulating fluid motion within the vasculature proximal to the thrombus,

wherein the circulating fluid motion facilitates contact of the thrombolytic agent with the thrombus by enhancing diffusion of the thrombolytic agent to the region of the blood vessel proximal to the thrombus and by refreshing contact of the thrombus with the thrombolytic agent, thereby providing more effective interaction of the thrombolytic agent with the thrombus.

12. The method of claim 11, wherein the thrombolytic agent is attached to the magnetic nanoparticles prior to introduction.

13. The method of claim 11, wherein the magnet is a permanent magnet rotatably coupled to a motor by a movable arm.

14. The method of claim 11, further comprising adjusting one or more of the position, the rotation plane and the rotation frequency of the magnetic field in response to one or more images of at least one of the region of the blood vessel in which the thrombus is located.

15. The method of claim 11, wherein said introducing a thrombolytic agent within vasculature of a subject is performed separately from administering the therapeutically effective amount of magnetic nanoparticles within the vasculature.

17. A method of treating a thrombus within a blood vessel of a subject through external magnetomotive manipulation of magnetic nanoparticles, the method comprising:

applying a magnetic field and a directed magnetic gradient of a magnet to a plurality of coated magnetic nanoparticles introduced within vasculature of a subject,

wherein the magnetic nanoparticles have a diameter between about 15 nm and 150 nm;

rotating the magnet at a first rotational frequency effective to agglomerate the magnetic nanoparticles into a plurality of magnetic nanoparticle rods having a length between 0.1 and 2 millimeters in response to the rotating magnetic field and the directed gradient; and

rotating the magnet at a second rotational frequency effective to move the magnetic nanoparticle rods along the vasculature in a walking end-over-end manner toward a thrombus in response to the rotating magnetic field and the directed gradient,

wherein the walking end-over-end manner of each of the rotating magnetic nanoparticle rods generates a circulating fluid motion within fluid proximal to the thrombus, thereby enhancing diffusion of a therapeutic agent to the thrombus and facilitating exposure of the therapeutic agent to the thrombus in response to the rotating magnetic field and the directed gradient.

18. The method of claim 17, further comprising causing the magnetic nanoparticle rods to travel through the vasculature by repeatedly:

a) walking end over end along the vasculature 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 vasculature towards the magnetic field in response to the rotation of the magnetic nanoparticle rods and the directed magnetic gradient.

19. The method of claim 17, wherein the first rotational frequency and the second rotational frequency are each between 1 Hz and 30 Hz, and wherein the first rotational frequency and the second rotational frequency are different.

20. The method of claim 17, wherein the first rotational frequency and the second rotational frequency are each between 1 Hz and 30 Hz, and wherein the first rotational frequency and the second rotational frequency are the same.

21. The method of claim 17, wherein the magnetic nanoparticles combine to form magnetic nanoparticle rods having a length between one and two millimeters when exposed to a rotating magnetic field having a magnitude of between 0.01 Tesla and 0.1 Tesla that is rotating at a rotational frequency between 3 and 10 Hz and to a magnetic gradient strength of between 0.01 Tesla/meter and 5 Tesla/meter.