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Title:
DEVICE FOR THERAPEUTIC PURPOSES ON HUMAN TISSUE, FOR INFLUENCING INJECTED MAGNETIC PARTICLES WITH AN ALTERNATING ELECTRO-MAGNETIC GRADIENT FIELD
Document Type and Number:
WIPO Patent Application WO/2001/017611
Kind Code:
A1
Abstract:
A new device for therapeutic influence, change, decomposition of various biological structures in vivo or in vitro by means of an externally applied alternating magnetic gradient field is described.

Inventors:
FREDRIKSSON SARAH (SE)
KRIZ DARIO (SE)
Application Number:
PCT/SE2000/001730
Publication Date:
March 15, 2001
Filing Date:
September 07, 2000
Export Citation:
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Assignee:
EUROP I OF SCIENCE AB (SE)
FREDRIKSSON SARAH (SE)
KRIZ DARIO (SE)
International Classes:
A61N1/40; A61N2/00; C12M1/42; A61N2/10; (IPC1-7): A61N2/04; A61N2/00
Foreign References:
US4983159A1991-01-08
US4303636A1981-12-01
US4662359A1987-05-05
Other References:
DATABASE WPI Week 199919, Derwent World Patents Index; AN 1999-222966, XP002908994
DATABASE WPI Week 199806, Derwent World Patents Index; AN 1998-061300, XP002908995
Attorney, Agent or Firm:
AWAPATENT AB (Box 5117 Malmö, SE)
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Claims:
CLAIMS
1. A device for increasing the thermal and/or kinetic energy of magnetically responsible particles, c h a r a c t e r i s e d in that it contains at least two magnetic field generating means, of which at least one is a coil, between which means an alternating magnetic gra dient field can be generated in a spatially defined area, into which spatially defined area human or animal tissue can be introduced, said alternating magnetic gradient field causing an increase of the thermal and/or kinetic energy of magnetically responsible particles which have been added to said tissue, the increased thermal and/or kinetic energy of the magnetically responsible particles selectively reducing, deactivating or destroying endoge nous or exogenous biological structures in said tissue.
2. A device as claimed in claim 1, c h a r a c t e r i s e d in that one of the magnetic field generat ing means is a permanent magnet.
3. A device as claimed in claim 1 or 2, c h a r a c t e r i s e d in that it contains at least two coils, and that these coils are fed with alternating currents having different frequencies and/or amplitudes and/or phases, or alternatively that said coils are fed with either the positive or the negative part of the fed alternating current.
4. A device as claimed in one or more of claims 13, c h a r a c t e r i s e d in that it is equipped with a thermostat for careful temperature control of said tis sue, and/or that it is equipped with variable time set ting for careful control of the time during which said tissue is exposed to the alternating magnetic gradient field.
5. A device as claimed in one or more of claims 14, c h a r a c t e r i s e d in that the alternating magnetic gradient field alternates with frequencies of up to 30 MHz, and that the field strength inside said coils amounts to at least 10 mT.
6. A device as claimed in one or more of claims 15, c h a r a c t e r i s e d in that said tissue consists of a body part or an inner organ or blood, which are re turned to the host organism after completed exposure to the alternating magnetic gradient field.
7. A device as claimed in one or more of claims 16, c h a r a c t e r i s e d in that said magnetically re sponsible particles comprise a core of a metal oxide and a coating containing antibodies or parts thereof and have a size of 0.1300 nm.
8. A device as claimed in one or more of claims 17, c h a r a c t e r i s e d in that said magnetically re sponsible particles have been added to the host organism before the exposure of its tissue to the alternating mag netic gradient field, or alternatively that said magneti cally responsible particles have been added to the tissue after the tissue has been temporarily removed from the host organism.
9. A device as claimed in one or more of claims 18, c h a r a c t e r i s e d in that said endogenous or ex ogenous biological structures consist of mammal cells, malignant cells, plant cells, nerve cells, bacteria, viruses, cellular organelles, cell membranes, cell walls, liposomes, proteins, protozoa, parasites, peptides, drugs, toxins, organic compounds, inorganic compounds, or combinations thereof.
10. A device as claimed in one or more of claims 1 9, c h a r a c t e r i s e d in that it is intended for in vivo or in vitro use for treating tumour diseases, endocrine disorders or infectious diseases.
Description:
DEVICE FOR THERAPEUTIC PURPOSES ON HUMAN TISSURE, FOR INFLUENCING INJECTED MAGNETIC PARTICLES WITH AN ALTERNATING ELECTRO-MAGNETIC GRADIENT FIELD.

The present invention relates to equipment for changing, weakening or destroying biological structures in vivo and in vitro by means of a magnetic gradient field.

BACKGROUND OF THE INVENTION Magnecism and magnetically responsible particles have been used for a long time in various b'ochemical and medical applications. When paramagnetic materials are ex- posed to an externally alternating homogeneous magnetic field, heat is generated due to hysteresis. This genera- tion of heat, in particular in combination with super- paramagnetic nanoparticles, is used in cancer therapy and is chen referred to as magnetic fluid hyp0erthermia (1).

A cancer cell normally has a higher tempera ure than a healthy cell and therefore does not tolerate as high a temperature rise as a healthy cell. Thus, cancer cells can be selectively destroyed or weakened without affecting the host organism. An alternative method is that the composition of the superparamagnetic parcicles is or such type that cancer cells are made n lake in said particles into the cell, whereby the temperature is raised more efficiently in the cancer cell ithout any considerable heat loss to the environment. This type of therapy has been found to be promising, which is de- scribed', inter alia, in the patent literature (2, 3, 4, ifthereisnoclinicallyapprovedmagnetic5),even equipmentequipmentfor this thetimebeing.for A cell interalia,composedoflipidsis, acids,whichbothhavepoorthermalconductiv-andfatty ity, which makes it difficult to fight the target cell onlyextracellularheatgeneratedbyefficientlywith hysteresis.

SUMMARY OF THE INVENTION According to the present invention, a device is pro- vided which solves the above-mentioned problems. Thus, a device is provided for increasing the thermal and/or ki- netic energy of magnetically responsible particles, said device containing at least two magnetic field generating means, of which at least one is a coil, between which means an alternating magnetic gradient field can be gen- erated in a spatially defined area, into which spatially defined area human or animal tissue can be introduced, said alternating magnetic gradient field causing an in- crease of the thermal and/or kinetic energy of magneti- cally responsible particles which have been added to said tissue, the increased thermal and/or kinetic energy of the magnetically responsible particles selectively re- ducing, deactivating or destroying endogenous or exoge- nous biological structures in said tissue.

In one embodiment of the invention, one of the mag- netic field generating means is a permanent magnet.

In another embodiment of the invention, the device contains at least two coils and these coils are fed with alternating currents having different frequencies and/or amplitudes and/or phases, or alternatively said coils are fed with either the positive or the negative part of the fed alternating current.

Furthermore, the device can suitably be equipped with a thermostat for careful temperature control of said tissue and/or with variable time setting for careful con- trol of the time during which said tissue is exposed to the alternating magnetic gradient field.

In one embodiment of the device, the alternating magnetic gradient field alternates with frequencies of up to 30 MHz and the field strength inside said coils amounts to at least 10 mT.

The tissue which is to be treated can be a body part or an inner organ or blood, which are returned to the

host organism after completed exposure to the alternating magnetic gradient field.

The magnetically responsible particles suitably com- prise a core of a metal oxide and a coating containing antibodies or parts thereof and have a size of 0.1- 300 nm.

The magnetically responsible particles have been added to the host organism before the exposure of its tissue to the alternating magnetic gradient field, or alternatively after the tissue has been temporarily re- moved from the host organism.

The endogenous or exogenous biological structures consist, for instance, of mammal cells, malignant cells, plant cells, nerve cells, bacteria, viruses, cellular organelles, cell membranes, cell walls, liposomes, pro- teins, protozoa, parasites, peptides, drugs, toxins, organic compounds, inorganic compounds, or combinations thereof.

According to one aspect, the device is intended for in vivo or in vitro treatment of tumour diseases, endo- crine disorders or infectious diseases.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic illustration of the behaviour of magnetically responsible materials in one embodiment of the device according to the invention.

Fig. 2 is a schematic illustration of the structure of one embodiment of the device according to the inven- tion for generating a magnetic gradient field with alter- nating gradient direction.

Fig. 3 is an illustration of an electronic circuit which can be used to feed the coils in one embodiment of the device according to the invention with alternating current.

DETAILED DESCRIPTION OF THE INVENTION By the present invention, a new device is provided for use in a completely new method which combines the generation of heat by hysteresis with a powerful intro-

duction of shearing forces. The shearing forces initiate dislocations in the biological structure, for instance in cell membranes, cell walls (in cases where the target cell is e. g. a bacterium) or in intracellular components due to mechanical fatigue, which causes damage in the structures. The method is based on the use of an exter- nally applied gradient magnetic field.

Below, the invention will be described in more de- tail by means of the drawings, which show embodiments of the invention.

Fig. 1 illustrates how a magnetically responsible particle is affected by a magnetic gradient field. With- out the action of an external magnetic field, the dipoles 1 in the magnetically responsible particles are randomly oriented (Fig. 1A). When the particles are exposed to a homogeneous magnetic field 2, the dipoles are oriented according to the direction of the field (Fig. 1B). When the direction of the homogeneous field alternates, the dipoles will alternate according to the field direction of the external homogeneous field. When the applied magnetic field is non-homogeneous, i. e. is a gradient magnetic field 3, the dipoles in the magnetically respon- sible particles will be aligned with the field direction at the same time as the magnetically responsible par- ticles will move towards the gradient according to Fig. 1C.

Furthermore, by alternating the direction of the gradient, the magnetically responsible particle can be brought into mechanical vibration (due to the influence of forces it will alternately change directions).

Moreover, a combination of said magnetic gradient field with a homogeneous magnetic field can be provided either simultaneously or with a time shift so that a better orientation of the dipoles and greater shearing forces can be obtained.

The generation of a gradient magnetic field whose direction periodically alternates (periodically shifts)

requires a device according to the invention, for in- stance, as illustrated in Fig. 2. The functional prin- ciple is based on two coils A and B (with or without a ferrite core) being placed opposite to each other. A control unit C controls the current through the coils so that only one of the coils at a time has a current flowing through its windings. This alternation of cur- rent, whose frequency is controlled by the oscillator (OSC), causes the coils to alternately create the gra- dient magnetic fields D and E with different gradient directions. A biological structure or a magnetically responsible particle P located between the coils will be exposed to a gradient magnetic field with periodically alternating direction, which will induce a mechanical vibration according to the description above.

The present invention also comprises variants, in which, for instance, the current intensity or its di- rection through the windings of the coils can be con- trolled so that more efficient vibrations can be ob- tained. A very useful special case is to let the gradient direction alternate but maintain the orientation of the dipoles by always letting the field direction be the same. This results in advantages, such as no provision of hysteresis (no generation of heat), while the vibration frequency (=kinetic energy) can be increased since the alternation rate of the dipoles will not be limited by the tendency of the magnetic material to counteract the alternation of the dipole directions.

It is also possible to introduce additional coils to obtain more efficient or more directional vibrations.

Fig. 3 illustrates an example of an electronic cir- cuit which can be used to feed the coils in the device according to the invention with alternating current. The circuit contains an oscillator 4 based on the circuit XR2206, whose output signal 5 is amplified by a power amplifying step 6, which is connected in parallel and based on 5 circuits of the type PBD 3548/1 (manufactured

by Ericsson), whose output signal 7 can drive an alter- nating current (maximum 1 MHz, 10 A) through one or more coils.

It is obvious to the one skilled in the art that the above-described electronic circuit in Fig. 3 is easy to modify and that the same result can be obtained by means of various alternative prior-art connections of oscil- lators and power amplifiers.

One example of the connection of the coils is that each coil constitutes a part of an oscillation circuit consisting of a 0.5 Q resistor, a 127 pF capacitor and a 200 H coil, which are connected in series, which oscil- lation circuit is fed with alternating current such as shown in Fig. 3.

An alternating gradient field is obtained between two coils which are part of said oscillation circuit and applied to an electronic circuit each, as shown in Fig. 3, with the difference, however, that the coils are fed with 1.0 MHz and 0.9 MHz, respectively. The variation of the gradient field will be dependent on the difference frequency 1.0 MHz-0.9 MHz.

It is obvious to the one skilled in the art that the above-described example is easy to modify and that the same result can be achieved by means of various alter- native connections and coils.

REFERENCES 1. Jordan A., Wust P., Scholz R., Faehling H., Krause J.

& Felix R. Magnet Fluid Hyperthermia, 569-597, in Scien- tific and Clinical Applications of Magnetic Carriers, edited by Hafeli U., Schutt W., Teller J. and Zborowski M. Plenum Press 1997.

2. Gordon R. T. Cancer treatment. US Patent No. 4,303,636, 1981.

3. Gordon R. T. Cancer treatment method. US Patent No.

4,662,952,1986.

4. Gordon R. T. Use of magnetic susceptibility probes in the treatment of cancer. US Patent No. 4,662,359,1987.

5. Borelli N. F., Luderer A. A. & Panzarino J. N. Radio frequency induced hyperthermia for tumor therapy.

US Patent No. 4,323,056,1982.