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WO2013028153A2 - Procédé et appareil d'élimination des substances toxiques contenues dans des cellules - Google Patents

Procédé et appareil d'élimination des substances toxiques contenues dans des cellules Download PDF

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Publication number
WO2013028153A2
WO2013028153A2 PCT/US2011/048411 US2011048411W WO2013028153A2 WO 2013028153 A2 WO2013028153 A2 WO 2013028153A2 US 2011048411 W US2011048411 W US 2011048411W WO 2013028153 A2 WO2013028153 A2 WO 2013028153A2
Authority
WO
WIPO (PCT)
Prior art keywords
cell
delivery vehicle
cells
noxious material
magnetic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2011/048411
Other languages
English (en)
Other versions
WO2013028153A3 (fr
Inventor
Irving N. Weinberg
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Weinberg Medical Physics LLC
Original Assignee
Weinberg Medical Physics LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Weinberg Medical Physics LLC filed Critical Weinberg Medical Physics LLC
Priority to PCT/US2011/048411 priority Critical patent/WO2013028153A2/fr
Publication of WO2013028153A2 publication Critical patent/WO2013028153A2/fr
Anticipated expiration legal-status Critical
Publication of WO2013028153A3 publication Critical patent/WO2013028153A3/fr
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis

Definitions

  • the presently disclosed embodiments relate to a novel approach for removing noxious material from cells.
  • Cells in nature behave in a manner to maintain homeostasis, which is the regulation of the cell's internal environment for maintaining a stable, constant condition.
  • cells may also create waste products as a result of the different chemical reactions used by the cell to survive. Thos chemical reactions may create waste that requires disposal in order to promote and maintain homeostasis and proper cell operation.
  • Figure 1 illustrates an example of various delivery vehicles containing magnetic particles with binding capabilities that may be brought into a region of cells containing noxious materials in accordance with the disclosed embodiments.
  • Figure 2 illustrates a stage of a method for removing noxious materials from a cell, wherein payload of delivery vehicles enters cells containing noxious materials in accordance with the disclosed embodiments.
  • Figure 3 illustrates a stage of a method for removing noxious materials from a cell, wherein payload of delivery vehicles binds to noxious materials in accordance with the disclosed embodiments.
  • Figure 4 illustrates a stage of a method for removing noxious materials from a cell, wherein payload of delivery vehicles, still bound to noxious materials, exits from the cell, without destroying cell in accordance with the disclosed embodiments.
  • Figure 5 illustrates a stage of a method for removing noxious materials from a cell, wherein noxious materials, now removed from cell, are eliminated by nearby glial cells in accordance with the disclosed embodiments.
  • an inventive concept implemented in a method and apparatus(es) remove noxious or unneeded materials from cells in a subject's body.
  • noxious refers to material which, upon excessive accumulation in a cell, can negatively affect the function of that cell. Hence the noxious material at low concentrations need not be poisonous.
  • delivery vehicles are transported to one or more regions of the subject's body affected by accumulation of noxious materials in the affected cells of those regions, where the term "noxious" is defined above.
  • the delivery vehicles may have such properties that they can enter into cells, bind within the cells to the noxious material, and then be removed from the cells with the noxious material attached thereto.
  • the conformation i.e., the structure or outline of an item or entity, determined by the arrangement of its parts of the delivery vehicle may change at various stages of the process.
  • the noxious materials may be destroyed by other cells (e.g., glial cells in the brain).
  • the delivery vehicles may be "magnetic particles,” which term includes the case of magnetic nanoparticles, which may be configured with or without surface or coatings.
  • the delivery vehicles may be microbubbles with internal or surface magnetic nanoparticles.
  • the delivery vehicles may be elongated, as in so-called “magnetic nanoworms.”
  • the delivery vehicles may themselves be cells or other living organisms.
  • Figure 1 illustrates an example of various delivery vehicles containing magnetic particles with binding capabilities that may be brought into a region of cells containing noxious materials in accordance with the disclosed embodiments. As shown in Fig. 1, the delivery vehicles contain magnetic particles with binding capabilities 1 that are brought into a region of cells 2 containing noxious materials 3.
  • the delivery vehicles 1 may be brought to the vicinity of cells 2 containing unwanted or abnormally high concentrations of noxious substances 3.
  • the delivery vehicles may be transported to the region of affected cells via a locally-placed catheter, or via magnetic guidance from the systemic or cerebrospinal circulation or a nearby-placed catheter, or via pores in natural orifices such as the cribiform plate (with or without magnetic guidance). It is known that it is possible to design magnetic nanoparticles to enter cells, as shown in the article: "Magnetic nanoparticles in MR imaging and drug delivery", by C Sun et al, published in Advanced Drug Delivery Reviews 60:1252-1265 (2008) (the disclosure of which being incorporated by reference in its entirety).
  • Figure 2 illustrates a stage of a method for removing noxious materials from a cell, wherein payload of delivery vehicles enters cells containing noxious materials in accordance with the disclosed embodiments. As shown in Fig. 2, these delivery vehicles 4 enter the cells 2 that contain the noxious materials 3.
  • entry of the delivery vehicle 1 into cells 2 may be as a result of a concentration gradient of delivery vehicles between the space outside the affected cells and the interior of the affected cells.
  • a concentration gradient could be established through the use of magnetic forces acting upon delivery vehicles containing magnetizable or magnetic particles, in which the magnetic forces created a high extracellular concentration of the particles in the affected region.
  • the delivery vehicles may enter the cells by phagocytosis.
  • the delivery vehicles may enter the cells via active transport.
  • the delivery vehicles may enter the cell or cell part and release their payload (e.g., of magnetic particles) 4.
  • electromagnetic radiation for example, radiofrequency
  • mechanisms may be used to transport and/or manipulate the delivery vehicle during various stages of operation including delivery of the delivery vehicle to and/or from a region of a subject's body, to facilitate or trigger entry of the delivery vehicle into the cell or cell part, to facilitate or trigger binding of the payload with the noxious materials, and/or to facilitate exit of the bound noxious materials from the cell or cell part.
  • the payload of the delivery vehicle may bind with the noxious material to be removed.
  • Figure 3 illustrates a stage of a method for removing noxious materials from a cell, wherein payload of delivery vehicles binds to noxious materials in accordance with the disclosed embodiments. As shown in Fig. 3, the payload of the delivery vehicles 4 binds to the noxious materials 3.
  • the delivery vehicles (or, alternatively only their payloads) bind to the noxious materials in the cell.
  • cells can tag abnormal proteins with ubiquitin, and that it is possible to make ligands that bind to the ubiquitin.
  • the conformation of the delivery vehicles or their payloads is altered, for example by application of electromagnetic radiation or electric or magnetic fields.
  • the presence of the magnetic nanoparticles, whether or not under the influence of an external magnetic field may alter the conformation of the noxious material in order to render it less noxious, with or without the need to remove the noxious material from the cell.
  • Figure 4 illustrates a stage of a method for removing noxious materials from a cell, wherein payload of delivery vehicles, still bound to noxious materials, exits from the cell, without destroying cell in accordance with the disclosed embodiments.
  • the payload of the delivery vehicles 4 remains bound to the noxious material during the exit of the payload material from the cell. Of particular note, this exit of the material does not destroy the cell.
  • the delivery vehicles (or, alternatively, only their payloads), now bound to the noxious materials, may be removed from the affected cells, or from internal parts of the affected cells (e.g., the nucleus) using a number of techniques.
  • the method of removal may include applying magnetic forces or gradients that act on magnetic particles to physically establish a velocity vector radiating outward from the cell or internal cell part.
  • the concentration gradient of the magnetic particles or delivery vehicles may be such that there is a tendency for them to exit from the cell or from the internal cell part without external manipulation.
  • the establishment of magnetic gradients may assist in creating such a concentration gradient.
  • the removal of the delivery vehicles may be enabled or promoted via exocytosis or other means of disposal from the cell or cell part.
  • electromagnetic radiation for example, radiofrequency
  • Figure 5 illustrates a stage of a method for removing noxious materials from a cell, wherein noxious materials, now removed from cell, are eliminated by nearby glial cells in accordance with the disclosed embodiments.
  • the noxious materials 3 may be removed from cell and subsequently eliminated by nearby glial cell 5 or some other naturally occurring or artificially induced mechanism.
  • the removed noxious materials, whether bound or unbound to the delivery vehicles (or the delivery vehicles' payloads) may be destroyed, neutralized or removed via various natural or artificially induced mechanisms.
  • this destruction may be implemented via natural defenders of the subject's own body, such as glial cells 5, that can act in the extracellular space but may be unable to act effectively on noxious materials that are inside other cells.
  • microglia can remove magnetic nanoparticles, as shown in the article "Robust Uptake of Magnetic Nanoparticles (MNPs) by Central Nervous System (CNS) Microglia: Implications for Particle Uptake in Mixed Neural Cell Populations", by MR Pickard and DM Chari, published in Int. J. Mol. Sci. 11:967-981 (2010) (the disclosure of which being incorporated by reference in its entirety).
  • MNPs Magnetic Nanoparticles
  • CNS Central Nervous System
  • the noxious materials are removed via diffusion or other natural transport processes and eliminated from the body.
  • the noxious materials may be transported in the bound state to the delivery vehicles (or the delivery vehicles' payloads) or dissociated from the bound state.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Treating Waste Gases (AREA)

Abstract

Procédé et appareil d'élimination des substances toxiques ou inutiles contenues dans les cellules du corps d'un patient.
PCT/US2011/048411 2011-08-19 2011-08-19 Procédé et appareil d'élimination des substances toxiques contenues dans des cellules Ceased WO2013028153A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2011/048411 WO2013028153A2 (fr) 2011-08-19 2011-08-19 Procédé et appareil d'élimination des substances toxiques contenues dans des cellules

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2011/048411 WO2013028153A2 (fr) 2011-08-19 2011-08-19 Procédé et appareil d'élimination des substances toxiques contenues dans des cellules

Publications (2)

Publication Number Publication Date
WO2013028153A2 true WO2013028153A2 (fr) 2013-02-28
WO2013028153A3 WO2013028153A3 (fr) 2014-03-20

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/048411 Ceased WO2013028153A2 (fr) 2011-08-19 2011-08-19 Procédé et appareil d'élimination des substances toxiques contenues dans des cellules

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Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8097164B2 (en) * 2007-11-08 2012-01-17 Electric Power Research Institute, Inc. Process for preparing magnetic particles for selectively removing contaminants from solution
US20120037840A1 (en) * 2008-02-25 2012-02-16 Galen Stucky Use of magnetic nanoparticles to remove environmental contaminants
AU2009260042A1 (en) * 2008-06-17 2009-12-23 Georgia Tech Research Corporation Superparamagnetic nanoparticles for removal of cells, pathogens or viruses

Also Published As

Publication number Publication date
WO2013028153A3 (fr) 2014-03-20

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