Controlling magnetic nanoparticles to increase vascular flow

• US 8,926,491 B2
• Filed: 09/06/2013
• Issued: 01/06/2015
• 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): Ball, J. Christopher
• Application Number:
  US14/020,173
• Publication Number:
  US 20140135564A1
• Time in Patent Office: 487 Days
• Field of Search: 600/12, 204/557, 335220-282
• 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 increasing fluid flow within vasculature of a subject through external magnetomotive manipulation of magnetic nanoparticles introduced within the vasculature, the method comprising:

introducing a therapeutic agent within vasculature of a subject;

infusing a plurality of magnetic nanoparticles within the vasculature in a manner such that dispersion of the magnetic nanoparticles within a solution is maintained during infusion,

causing a magnet external to the vasculature and having a magnetic field and a directed magnetic gradient to be positioned and to rotate in a manner sufficient to i) agglomerate the magnetic nanoparticles into a plurality of agglomerates within the vasculature and ii) travel within the vasculature toward a therapeutic target in an end over end manner in response to the rotating magnetic field and the directed magnetic gradient of the magnet; and

causing the agglomerates to collectively generate a circulating fluid motion within the vasculature proximal to the therapeutic target by adjusting at least one parameter selected from the group consisting of;

a rotational frequency of the rotating magnetic field, a plane of the rotating magnetic field with respect to the therapeutic target, and a distance of the rotating magnetic field with respect to the therapeutic target,

wherein the circulating fluid motion facilitates contact of the therapeutic agent with the therapeutic target by enhancing diffusion of the therapeutic agent to the therapeutic target and by refreshing contact of the therapeutic target with the therapeutic agent, thereby providing more effective interaction of the therapeutic agent with the therapeutic target.

2. The method of claim 1, wherein the therapeutic agent is a thrombolytic drug.

3. The method of claim 1, wherein the therapeutic target is a clot in a cerebral blood vessel.

4. The method of claim 1, wherein the therapeutic target is an embolism.

5. The method of claim 1, wherein the therapeutic target is a fluid blockage in an extremity of the subject.

6. The method of claim 1, wherein the therapeutic target is a coronary occlusion.

7. The method of claim 1, wherein the therapeutic target is selected from the group consisting of:

fatty buildup, arterial stenosis, arterial restenosis, vein thrombi, arterial thrombi, and cerebral thrombi.

8. The method of claim 1, wherein the therapeutic agent is attached to the magnetic nanoparticles prior to introduction.

9. The method of claim 1, wherein the therapeutic agent is introduced within the vasculature separate from the magnetic nanoparticles.

10. The method of claim 1, wherein the magnet is a permanent magnet.

11. The method of claim 1, further comprising causing the motor to position the magnet at an effective distance and an effective plane with respect to the therapeutic target, and to rotate the magnet at frequency between 1 Hz and 30 Hz.

12. A method of increasing fluid flow within a blood vessel of a subject through external magnetomotive manipulation of magnetic nanoparticles introduced within the subject, the method comprising:

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

administering a plurality of magnetic nanoparticles within the vasculature at a controlled infusion rate;

causing a magnet external to the vasculature and having a magnetic field and a directed magnetic gradient to be positioned and to rotate in a manner sufficient to i) agglomerate the plurality of magnetic nanoparticles within the vasculature to form a plurality of agglomerates and ii) travel within the vasculature toward the fluid obstruction within the blood vessel in an end over end manner in response to the rotating magnetic field and the directed magnetic gradient of the magnet; and

causing the agglomerates to collectively generate a circulating fluid motion within the blood vessel proximal to the fluid obstruction by adjusting at least one parameter selected from the group consisting of;

a frequency of the rotating magnetic field, a plane of the rotating magnetic field with respect to the fluid obstruction, and a distance of the rotating magnetic field with respect to the fluid obstruction, thereby increasing contact of the therapeutic agent with the fluid obstruction.

13. The method of claim 12, wherein introducing a thrombolytic agent within vasculature of a subject is performed separately from administering the plurality of magnetic nanoparticles within the vasculature.

14. The method of claim 12, wherein the magnet is a permanent magnet.

15. The method of claim 12, wherein the thrombolytic agent is tissue plasminogen activator.

16. The method of claim 12, wherein the fluid obstruction is selected from the group consisting of:

a cerebral thrombus, a clot in vasculature of the extremities, a coronary occlusion and an embolism.

17. A method of increasing fluid flow within vasculature of a subject through external magnetomotive manipulation of magnetic nanoparticles introduced within the vasculature, the method comprising:

providing a magnetic control system configured for;

causing a magnet external to vasculature of a subject and having a magnetic field and a directed magnetic gradient to be positioned and to rotate in a manner sufficient to i) agglomerate a plurality of magnetic nanoparticles previously introduced into the vasculature into a plurality of agglomerates and ii) travel within the vasculature toward a therapeutic target in an end over end manner in response to the rotating magnetic field and the directed magnetic gradient of the magnet; and

causing the agglomerates to collectively generate a circulating fluid motion within the vasculature proximal to the therapeutic target by adjusting at least one parameter selected from the group consisting of;

a rotational frequency of the rotating magnetic field, a plane of the rotating magnetic field with respect to the therapeutic target, and a distance of the rotating magnetic field with respect to the therapeutic target, thereby increasing contact of a therapeutic agent previously introduced within the vasculature with the therapeutic target.

18. The method of claim 17, further comprising infusing the magnetic nanoparticles within the vasculature.

19. The method of claim 17, further comprising infusing the therapeutic agent within the vasculature.

20. The method of claim 17, wherein the magnetic control system comprises a user interface having a touchscreen display.