CA2365403A1 - Heating of magnetic material by hysteresis effects - Google Patents
Heating of magnetic material by hysteresis effects Download PDFInfo
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- CA2365403A1 CA2365403A1 CA002365403A CA2365403A CA2365403A1 CA 2365403 A1 CA2365403 A1 CA 2365403A1 CA 002365403 A CA002365403 A CA 002365403A CA 2365403 A CA2365403 A CA 2365403A CA 2365403 A1 CA2365403 A1 CA 2365403A1
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- A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
- A61N1/403—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia
- A61N1/406—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals for thermotherapy, e.g. hyperthermia using implantable thermoseeds or injected particles for localized hyperthermia
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- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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Abstract
A magnetic material having a magnetic heating efficiency of at least 4.5 x 10-8 J.m/A.g in a cyclic magnetic field where the product of the amplitude and frequency of the applied field is less than or equal to 5 x 108 A/m.s, and the frequency of the applied field is at least 20kHz. The ideal magnetic material is characterised by a perfectly rectangular hysteresis loop, i.e. loop squareness of 1, with coercivity of 25kA/m or less and high saturation magnetisation. Preferably the magnetic material has a predominantly cubic magnetic crystalline anisotropy. Preferably the magnetic material is a substituted magnetite (Fe3O4) or .gamma.-ferric oxide (.gamma.-Fe2O3) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms.
Desirably, the metal atom is a member of the group: cobalt, zinc, nickel, manganese, magnesium, copper, chromium, galliun, cadmium.
Desirably, the metal atom is a member of the group: cobalt, zinc, nickel, manganese, magnesium, copper, chromium, galliun, cadmium.
Description
Heating Of Magnetic Material By Hysteresis Effects -FIELD OF INVENTION
The present invention relates to magnetic materials. More particularly, the invention relates to magnetic materials that exhibit high magnetic hysteresis heating in a cyclic magnetic field.
BACKGROUND ART
Each time a ferromagnetic material is exposed to a magnetic field whose amplitude and/or direction varies cyclically in time a small amount of energy is dissipated as heat due to magnetic hysteresis effects. The more rapidly the field is cycled, the greater the rate at which heat is produced by the material. By improving the rate at which a magnetic material heats, it is possible to maximise the potential uses to which this technology may be applied.
One means that has been used to increase the rate at which heat is produced by a magnetic material is to apply a rotating magnetic field to that material rather than the more usual linear alternating field. In our earlier co-owned patent application ("Improved Targeted Hysteresis Hyperthermia for Treating Diseased Tissue"), we have shown that under certain conditions of magnetic field strength and frequency, rotating fields cause far greater heating of magnetic materials compared to a linear alternating field, hence greater heating efficiency is achieved.
Another means to increase the rate at which heat is produced by a material is to improve the magnetic profile of the material and to select materials that display high heating efficiency. Thus, the need to maximise the heating efificiency of the magnetic particle is paramount.
Magnetic materials with an improved magnetic heating efficiency have application in any circumstances where localised heating of unexposed areas is required.
For example, the materials may be used in such diverse situations as in rapid heating of cements or epoxies or in the treatment of cancer by hyperthermia therapy.
The present invention relates to magnetic materials. More particularly, the invention relates to magnetic materials that exhibit high magnetic hysteresis heating in a cyclic magnetic field.
BACKGROUND ART
Each time a ferromagnetic material is exposed to a magnetic field whose amplitude and/or direction varies cyclically in time a small amount of energy is dissipated as heat due to magnetic hysteresis effects. The more rapidly the field is cycled, the greater the rate at which heat is produced by the material. By improving the rate at which a magnetic material heats, it is possible to maximise the potential uses to which this technology may be applied.
One means that has been used to increase the rate at which heat is produced by a magnetic material is to apply a rotating magnetic field to that material rather than the more usual linear alternating field. In our earlier co-owned patent application ("Improved Targeted Hysteresis Hyperthermia for Treating Diseased Tissue"), we have shown that under certain conditions of magnetic field strength and frequency, rotating fields cause far greater heating of magnetic materials compared to a linear alternating field, hence greater heating efficiency is achieved.
Another means to increase the rate at which heat is produced by a material is to improve the magnetic profile of the material and to select materials that display high heating efficiency. Thus, the need to maximise the heating efificiency of the magnetic particle is paramount.
Magnetic materials with an improved magnetic heating efficiency have application in any circumstances where localised heating of unexposed areas is required.
For example, the materials may be used in such diverse situations as in rapid heating of cements or epoxies or in the treatment of cancer by hyperthermia therapy.
Where rapid heating of cements or epoxies is required for rapid curing without heating the nearby surfaces or objects, magnetic particles may be dispersed evenly throughout the cement or epoxy (only several parts per thousand would be needed) such that subsequent application of a cyclic magnetic field would cause uniform heating throughout the volume of the cement rather than just heating from the outside in.
In our previous patent applications, "Targeted Hysteresis Hyperthermia as a Method for Treating Diseased Tissue" and "Improved Targeted Hysteresis Hyperthermia for Treating Diseased Tissue", we disclose techniques for the localised heating of tumours using heat generated by small magnetic particles exposed to a time varying magnetic field. Magnetic particles are incorporated into biocompatible microcapsules that are administered in such a manner that they concentrate in the vascular network surrounding a tumour. A cyclic magnetic field is applied externally and heat from the microcapsules is conducted into the surrounding tumour tissue. Use of appropriately formulated microcapsules, magnetic field conditions and microcapsule dosage ensures that the tumours are heated to lethal temperatures, i.e. above about 42°C, whilst simultaneously sparing healthy tissue.
There are various ways to deliver the magnetic particles to tumours. For example, the magnetic particles can be administered by direct injection into the tumour tissue. In this way it is possible to get large quantities of material into the tumour. Hence, it may be possible to heat tumours to therapeutic levels using magnetic particles with inferior properties.
An alternative route of administration would demand delivery of the magnetic material preferably in microcapsule form via intra-vascular infusion to target the vascular network surrounding the tumour. This technique is preferred since it offers some significant advantages that improve the therapeutic effectiveness compared to direct injection into tumour. These advantages include the following:
(i) The less invasive nature of the delivery technique reduces the likelihood of inadvertent spreading of the cancer;
In our previous patent applications, "Targeted Hysteresis Hyperthermia as a Method for Treating Diseased Tissue" and "Improved Targeted Hysteresis Hyperthermia for Treating Diseased Tissue", we disclose techniques for the localised heating of tumours using heat generated by small magnetic particles exposed to a time varying magnetic field. Magnetic particles are incorporated into biocompatible microcapsules that are administered in such a manner that they concentrate in the vascular network surrounding a tumour. A cyclic magnetic field is applied externally and heat from the microcapsules is conducted into the surrounding tumour tissue. Use of appropriately formulated microcapsules, magnetic field conditions and microcapsule dosage ensures that the tumours are heated to lethal temperatures, i.e. above about 42°C, whilst simultaneously sparing healthy tissue.
There are various ways to deliver the magnetic particles to tumours. For example, the magnetic particles can be administered by direct injection into the tumour tissue. In this way it is possible to get large quantities of material into the tumour. Hence, it may be possible to heat tumours to therapeutic levels using magnetic particles with inferior properties.
An alternative route of administration would demand delivery of the magnetic material preferably in microcapsule form via intra-vascular infusion to target the vascular network surrounding the tumour. This technique is preferred since it offers some significant advantages that improve the therapeutic effectiveness compared to direct injection into tumour. These advantages include the following:
(i) The less invasive nature of the delivery technique reduces the likelihood of inadvertent spreading of the cancer;
(ii) Target tumours do not need to be accurately located and exposed to enable injection of the particles;
(iii) A more optimal distribution of heating foci within the tumour will almost certainly obtain using the intra-vascular infusion technique; and (iv) It will be easier to treat a large number of small nodules such as often occurs in the case of metastastic liver cancer.
A feature of this route of administration is that a smaller number of particles are delivered to the diseased tissue compared to direct injection. Hence, improvements of the heating characteristics of the magnetic particles are extremely important in order to enable treatment of tumours using intra-vascular infusion.
We have previously specified the minimum operating constraints in terms of the strength of the applied field and its frequency assuming whole body exposure to the field. These stipulated field conditions for whole body exposure are that the frequency should be greater than about lOkHz and the product of frequency and field strength should not exceed 5x108 A/m.s. We have also stipulated the minimum Magnetic Heating Efficiency (MHE) which must be achieved by the magnetic microcapsules subject to these conditions.
Certain commercially available materials do perform according to the stipulated conditions, however it is clear that any improvement in the heating efficiency subject to the imposed constraints, would significantly enhance the usefulness of this and other heating techniques.
The present invention seeks to provide a magnetic material with improved magnetic heating characteristics that can be used in diverse methods such as, but not limited to, the heating of cements and in the treatment of diseased tissue.
Throughout the specification, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
(iii) A more optimal distribution of heating foci within the tumour will almost certainly obtain using the intra-vascular infusion technique; and (iv) It will be easier to treat a large number of small nodules such as often occurs in the case of metastastic liver cancer.
A feature of this route of administration is that a smaller number of particles are delivered to the diseased tissue compared to direct injection. Hence, improvements of the heating characteristics of the magnetic particles are extremely important in order to enable treatment of tumours using intra-vascular infusion.
We have previously specified the minimum operating constraints in terms of the strength of the applied field and its frequency assuming whole body exposure to the field. These stipulated field conditions for whole body exposure are that the frequency should be greater than about lOkHz and the product of frequency and field strength should not exceed 5x108 A/m.s. We have also stipulated the minimum Magnetic Heating Efficiency (MHE) which must be achieved by the magnetic microcapsules subject to these conditions.
Certain commercially available materials do perform according to the stipulated conditions, however it is clear that any improvement in the heating efficiency subject to the imposed constraints, would significantly enhance the usefulness of this and other heating techniques.
The present invention seeks to provide a magnetic material with improved magnetic heating characteristics that can be used in diverse methods such as, but not limited to, the heating of cements and in the treatment of diseased tissue.
Throughout the specification, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
Disclosure of the Invention The present invention consists in a magnetic material having a magnetic heating efficiency of at least 4.5 x 10-$ J.m/A.g in a cyclic magnetic field where the product of the amplitude and frequency of the applied field is less than or equal to 5 x 108 A/m.s, and the frequency of the applied field is at least 20 kHz.
The ideal magnetic material is characterised by a perfectly rectangular hysteresis loop, i.e. loop squareness, defined by the ratio of the remanent to saturation magnetisation equal to 1, with coercivity of 25kA/m or less and high saturation magnetisation. Such a situation is difficult to achieve with an array of randomly aligned particles as is the case when the magnetic materials are dispersed in compositions such as cement or epoxies or in biological tissues.
Preferably, the magnetic material has a predominantly cubic magnetocrystalline anisotropy. Particles with predominantly cubic magnetocrystalline anisotropy come closest to approaching the specified behaviour in a cyclic magnetic field since they can have a hysteresis loop squareness as high as 0.86.
For a random array of particles with other types of anisotropy (e.g. uniaxial anisotropy), loop squareness will not generally exceed 0.5. In considering arrays of particles with the same coercivity but different loop squareness, the maximum value of hysteresis work per cycle (i.e. either Wa or ~V~) will occur at a higher field for the array with the lower loop squareness. This means the magnetic heating efficiency for these particles will be less than for the particles with higher loop squareness.
Having regard for the field-frequency constraint discussed above, the maximum allowable applied field strength at 20kHz is 25kA/m (314 Oe), decreasing proportionately as frequency is increased beyond 20kHz. Hence, the magnetic material desirably has a coercivity of less than 314 Oe. In addition, the remanence of the material should remain at a level that maximises the MHE.
In one embodiment of the present invention, there is provided a magnetic material having a coercivity of less than 314 Oe and a MHE of at least 4.5 x 10-$
J.m/A.g in a cyclic magnetic field where the product of the amplitude and frequency of the applied field is not more than 5 x 1 O8 A/m.s, and the frequency of the applied field is at least 20 kHz. In a preferred form of the invention the coercivity is less than 200 Oe.
The present invention should be understood to encompass any magnetic material that has the above mentioned characteristics. Preferably, the magnetic material is a substituted magnetite (Fe304) or y-ferric oxide (y-Fe203) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms. Desirably, the metal atom is a member of the group: cobalt, zinc, nickel, manganese, magnesium, copper, chromium, gallium, cadmium. In this respect the substituting metal atoms) may either be entirely selected from the same atomic species or a plurality of different metal atoms can be incorporated into the crystalline lattice.
While it will be appreciated that any of the above mentioned metal atoms may be substituted for iron atoms in the magnetite (Fe304) or y-ferric oxide (y-Fe203) crystalline lattice, the magnetic material must be possessed of a predominantly cubic magnetocrystalline anisotropy. Preferably, the substituting metal atoms are dispersed in a substantially even manner throughout the crystalline lattice.
When dispersed in such a manner the magnetic material tends to have a more predictable heating efficiency compared to the situation where the substituting metal atoms are all located in one region of the crystalline lattice.
In a highly specific form of the invention, the alternate metal atoms are cobalt atoms, and the magnetic material is a substituted magnetite (Fe304) or y-ferric oxide (y-Fe203) crystalline lattice. Where cobalt is the substituting metal atom the degree of substitution is preferably less than about 4% of the iron atoms in the crystalline lattice, more preferably in the range 0.2 and 3.5%.
In addition to being substituted preferably the magnetic material is provided in particulate form, with particles possessing equant morphology, such as simple cubic or spherical shapes, and being of a size between 20nm and 1 Vim.
To the extent that the present invention is to be used in the treatment of diseased tissue, there are several undesirable physiological effects that occur in response to sufficiently high rate of change of magnetic field, or d8/dt. These effectively impose limits on the frequency and strength of the magnetic field used in this application. These physiological responses are (i) cardiac muscle stimulation, (ii) peripheral nerve stimulation, and (iii) tissue heating due to eddy current generation.
To avoid cardiac muscle stimulation the frequency applied in the cyclic magnetic field should be greater than lOkHz. Preferably, a frequency limit of 20kHz is imposed to stay above the audible range, an important consideration for patient and operator comfort. Operating above 20kHz is highly desirable since this frequency is above the audible range and so patient and operator comfort is substantially improved over that at lower frequencies where the noise may be at an uncomfortable level.
In addition to the above where the present invention is used in hyperthermic treatment of cancer, the MHE of that material is preferably such as to enable production of sufficient heat to raise the temperature of the cancerous tissue to 42°C, being the minimum temperature required for therapeutic effect.
The scenario that demands the highest MHE from the magnetic material is likely to be the one where the magnetic material is delivered in the form of microcapsules to the site of the cancer via intra-arterial infusion.
The relatively small number of microcapsules that can be delivered via intra-arterial infusion means that each particle should be adapted to produce more heat in order to obtain the same therapeutic benefit. Preferably the magnetic material is to be capable of producing a minimum of 22.5 Watts per gram of material when exposed to the cyclic magnetic field.
Advantages gained by using a magnetic material within the scope of the present invention include:
1 ) improved therapeutic effectiveness by virtue of the fact that higher tumour temperatures can be reached more quickly (the effectiveness of hyperthermia therapy improves markedly as temperature is increased beyond 42°C);
2) reduced toxic side effects because:
_7_ i/. less microcapsules need to be used to achieve therapeutic heating in tumours (advantageous if the microcapsules have any intrinsic toxicity), ii/. more rapid heating of the tumour may be achieved which implicates less of the healthy tumour tissue immediately surrounding the tumour (the longer time required to heat the tumour the more the immediately surrounding tissue will be heated by thermal conduction);
3) increased likelihood of successful treatment especially for tumours that would otherwise be expected to only receive a marginal benefit;
4) the techniques have a wider applicability for the treatment of different types of cancer;
5) using reduced field strengths eases engineering difficulties associated with machine design;
In another embodiment there is provided a method for the production of a magnetic material within the scope of the present invention, the method comprising the steps of:
(i) dissolving a water-soluble salt of iron and one or more water-soluble salts of one or more alternate metal ions in aqueous solution;
(ii) co-precipitating hydroxides of iron and cobalt or each alternate metal ion from this solution;
(iii) treating the co-precipitated hydroxides in an aqueous medium with an oxidising agent which transforms the hydroxides into ferromagnetic iron oxides containing cobalt or each alternate metal ion;
(iv) separating the oxides from the aqueous medium, then drying and heating the oxides in an oxidising gaseous medium to a temperature not surpassing 500°C.
The oxide may be dried in a gaseous oxidising medium at a temperature between about 200-350°C. Alternatively, the oxides are heated in a gaseous oxidising medium to approximately 400°C before being slowly cooled to room temperature WO 00/52714 PC'~/AU00/00151 _g_ while being rotated in a magnetic field. Typically, the magnetic field has a rotational frequency of about 60 r.p.m. and a field strength of about 3 kOe.
In one form of the invention, the hydroxides are precipitated in conditions which cause the precipitated hydroxides to contain 1-20 atomic percent of iron in the trivalent form, the remainder being in divalent form. In a more specific form of the invention, the hydroxides are precipitated in conditions which cause the precipitated hydroxides to contain 5-15 atomic percent of iron in the trivalent form, the remainder being in divalent form.
The water-soluble salt of iron used in the preparation of the aqueous solution may be organic or inorganic. For example, the water-soluble salt of iron used in the preparation of the aqueous solution may be iron sulphate.
The water-soluble salt of cobalt or each alternate metal ion used in the preparation of the aqueous solution may also be organic or inorganic. Where the further alternate ion is cobalt, the water-soluble salt may be cobalt sulphate.
The co-precipitation of the hydroxides may be induced by the addition of an alkaline agent such as an alkali or alkaline earth metal hydroxide.
Typically, the co-precipitation of hydroxides is carried out at 5-30°C.
Suitable oxidising agents include nitrates, such as potassium-, sodium-, ammonium-nitrate, water soluble chlorates, such as sodium chlorate, persulfates such as sodium persulfate, H202 and oxygen.
The oxidation of the co-precipitated hydroxides is advantageously carried out at temperatures between about 50°C and the boiling point of the solution.
In a specific form of the invention, oxidation of the co-precipitated hydroxides takes place at temperatures of about 65-90°C.
In a further embodiment there is provided a method for production of a magnetic material within the scope of the invention, the method comprising the steps of:
(i) Procurement of non-magnetic cubic precursor particles;
-g_ (ii) Coating of the non-magnetic cubic precursor particles to prevent sintering of the particles;
(iii) Reduction of the non-magnetic cubic precursor particles to magnetite; and (iv) Oxidization of magnetite to y-ferric oxide (y-Fe203).
An example of a non-magnetic cubic precursor particles is haematite particles.
Methods for Precipitation of Haematite Precursors 1. In a first method for precipitation of uniform a-Fe203 particles, a dilute solution of an iron(III) salt was heated at reflux in dilute acid for at least 24 hours. The iron(III) salt used was the chloride salt. Nitrate or perchlorate salt can also be used. The corresponding acid used was hydrochloric acid. However nitric or perchloric acid are also appropriate. 0.4 mol/L FeCl3 (l0ml), 0.032 mol/L HCI
(25m1) and D.I. water (365 ml) were preheated to 100 deg. C, then mixed and maintained at reflux for 48 hours. The resulting precipitate was collected by centrifugation and washed by repeated centrifugation/re-suspension cycles in D.I. water, or by dialysis with D.I. water for a period of days.
2. In a second method for precipitation of uniform a-Fe203 particles, a concentrated iron(III) hydroxide gel was aged for a period of days at 100 deg.
C. The hydroxide gel was formed by mixing an equivalent amount of a strong base, being sodium hydroxide with a solution of an iron(III) salt. Potassium hydroxide is another strong base which can also be used for mixing with a solution of an iron (III) salt. 6.0 mol/L NaOH solution (65m1) was slowly added to a stirred solution of 2.OM FeCl3 (65 ml) in a 125m1 Erlenmeyer flask. The flask was then sealed and placed in an oven, preheated to 100°C, for 24 hours. The resulting precipitate was collected by centrifugation and washed by repeated centrifugation/re-suspension cycles in D.I. water, or by dialysis with D.I. water for a period of days.
Surface Treatment and Drying In order to prevent sintering of non-magnetic cubic precursor particles during reduction, the particles can be coated with a surfactant such as oleic acid, stearic acid or other long-chain carboxylic acids. Other anionic surfactants such as sodium dodecyl benzene sulphonate (SDBS) may also be used.
Method for Surface Treatment and Drying A haematite suspension (100m1) containing about 0.25g a-Fe203 was warmed to about 60 deg. C with stirring and rendered basic (~pH 11 ) by addition of a little NaOH solution (1 mol/L). A 1 % (w/w) solution of sodium stearate (5 ml) was added and the suspension stirred and heated gently for a further 15 minutes.
The mixture was then acidified by addition of HCI and transferred to a separating funnel and when cool, the stearate-coated a-Fe203 is extracted into 130 ml hexane. After washing excess stearic acid from the organic phase with a few aliquots of D.I. water, the hexane phase is evaporated to dryness at 50-70°C
under reduced pressure.
Reduction of Haematite to Magnetite Non-magnetic cubic precursor particles such as a-Fe203 may be converted to magnetic Fe304 by heat treatment in a reducing gas such as hydrogen or carbon monoxide. The reduction may be carried out at temperatures between 350 and 450°C and at gas flow rates of 100m1/min or greater. Ideally the reduction is carried out in an atmosphere of 5% hydrogen and 95% nitrogen at a temperature of 400°C over a period of at least 1 hour.
Oxidation of Magnetite Oxidation of magnetite to y-Fe203 is carried out by heat treatment in an oxidising gaseous medium. The magnetite may be dried in a gaseous oxidising medium at a temperature between about 200-350°C. Alternatively, the magnetite is heated in a gaseous oxidising medium to approximately 400°C before being slowly cooled to room temperature while being rotated in a magnetic field. Typically, the magnetic field has a rotational frequency of about 60 rpm and a field strength of about 3kOe.
The present invention further provides an improved method for site specific treatment of diseased tissue in a patient, which comprises the steps of:
(i) delivering the magnetic material of the present invention to diseased tissue in a patient; and (ii) exposing the magnetic material in the patient to a cyclic magnetic field with a frequency of greater than about 20kHz and a field strength selected such that the product of field strength, frequency and the radius of the exposed region is less than about 7.5 x 10' A/s to generate hysteresis heat in the diseased tissue.
Preferably, step (ii) is carried out for sufficient time to generate enough heat from the administered magnetic material to raise the tumour temperature above about 42 ° C. It will be appreciated that the amount of time for treating a tumour will largely depend on the size, position and physical structure of the tumour.
Most preferably step (ii) is repeated until the diseased tissue has been destroyed or treated sufficiently to ameliorate the disease.
The method of the invention provides a means to increase temperature in the area of diseased tissue to above 41 °C to decrease the viability of malignant cells.
A decrease in the viability of malignant cells results in either cell death or increased cell sensitivity to the effects of ionising radiation or chemotherapeutic drugs.
During treatment, patients are placed into a machine that generates a cyclic magnetic field. The cyclic magnetic field could be, for example, either a linear alternating magnetic field or a rotating magnetic field of strength H and frequency f.
In a linear alternating magnetic field the amplitude of the field varies sinusoidally along a fixed directional axis between a maximum positive amplitude and a maximum negative amplitude at a frequency of f. The magnetic field strength as a function of time, Ha(t), is described mathematically by Halt) = HaSin(2rctt) (1 ) where Ha is the magnetic field amplitude.
A rotational magnetic field can be described mathematically as the superposition of two orthogonal linear alternatirig magnetic fields with a n/2 phase difference, i.e.
Hr(t) = H,~Sin(2rdt) + HYSin(2rc~t+~r12) (2) where HX and Hy are the amplitudes of linear alternating magnetic fields directed in the X and Y directions respectively which combine to give Hr and f is their frequency of alternation. In this case the amplitude of the field remains constant but the direction of the field rotates with angular frequency of 2r~f. An advantage of the use of a rotational magnetic field compared to a linear alternating magnetic field of the same frequency and amplitude is that it leads to higher magnetic heating efficiency of the magnetic materials under some conditions. This in turn means that lower frequency and field strengths can be used in the method, if desired.
In order that enough hysteresis heat is generated by the magnetic material the cyclic magnetic field used in the method desirably has a relatively high frequency.
The higher the frequency the greater the rate of heating in the tissues that contain the magnetic material. However, the physiological response to high amplitude, high frequency magnetic fields limit the field amplitude and frequency that can be used in any clinical application. These limitations result from nerve muscle activation and eddy current heating which depends, inter alia, on the electrical conductivity of the tissue. Both of these are as a result of the electric fields induced in the tissue by the magnetic field.
3 _ Preferably, the magnetic material is mixed in a liquid emulsion or is formed -into microcapsules which may then be mixed with a suitable biocompatible medium for delivery into a patient. Most preferably the magnetic material is bound in a matrix material to form a microcapsule. Most magnetic particles themselves are, typically, too small and too dense to enable optimum delivery to the site of diseased tissue. Therefore, they are desirably encapsulated in microcapsules.
Important properties of microcapsules are their density and their diameter.
The density affects the efficiency of their carriage by the blood stream to the site of immobilisation in the diseased tissues vascular network while the size determines the proximity of the point of immobilisation to the diseased tissue.
Preferably, the magnetic material is bound in a matrix material which does not adversely affect the hysteresis or eddy current heating properties of the magnetic particles. The non-toxic binder or matrix material may comprise any of the suitable non-toxic materials which are well known in the microencapsulation art.
Suitable materials include, for example, proteins, polymeric resins such as styrene-divinylbenzene, biopol, albumin, chitosan etc.
In a preferred form of the invention, the microcapsules are adapted to bind or absorb or contain a cytotoxic material which is released upon heating of the microcapsule. For example the microcapsule may be composed of a porous, heat sensitive material which is non-toxic to and, preferably, inert to or compatible with animal tissue and which has embedded within it suitable magnetic material. The pores in the material are desirably filled with the cytotoxic compound. Upon hysteresis heating the micro-particles are capable of expanding, thereby permitting the release of the cytotoxic compound. Such particles should, however, be resistant to melting upon hysteresis heating. Thus, the use of such particles in the method of the present invention provides a single device with which combined chemotherapy and thermotherapy can be achieved to treat diseased tissue in a patient.
Another alternative delivery technique could be the injection or intra-vascular infusion of a suitable ferrocolloid which could consist, for example, of a suspension of magnetic microparticles in a liquid medium such as lipiodol. In this case the magnetic particles could range in size from subdomain nanometer size up to several microns.
A combination of different types of microcapsules may also be administered at the time of treatment to provide a multimode treatment. Microcapsules may be either radioactive microcapsules or chemotherapeutic microcapsules together with the hyperthermic microcapsules described. Further, the targeted hyperthermia therapy may be used in conjunction with conventional radiotherapy and/or chemotherapy. The choice of treatments will depend upon the specific details of each case as it presents.
According to a further embodiment of the invention, an ionising radiation source may be applied to the locus of the diseased tissue in conjunction with a magnetic field, said tissue having microcapsules as herein described included therein.
The radiation source may be microcapsules which contain a radioactive compound such as Yttrium-90 or delivered from an external radiation source.
An additional application of magnetic materials with the properties described in this application would be for use in antipilferage devices, or Electronic Article Surveillance (EAS) devices. Here, a magnetically very soft material is combined with a semi-hard material to make a label or tag that can be attached to an article in, say, a shop or library. If an attempt is made to move the article through a detection gate without first deactivating the tag then an alarm is sounded.
The tags are deactivated by magnetising the semi-hard material using a deactivator tablet that contains strong permanent magnets. The semi-hard magnetic material may also be used to provide a permanent bias field for the soft component. The magnetic characteristics of the magnetic materials described in this patent application make them well suited for use as the semi-hard component of the antipilferage devices.
BEST MODES) FOR CARRYING OUT THE INVENTION
In the drawings:
Figure 1 illustrates a typical form of alternating hysteresis work per cycle, Wa, as a function of applied field, Ha.
Figure 2 illustrates a typical form of rotational hysteresis work per cycle, W,, as a function of applied field, H~.
Figure 3 shows MHE data measured for 3 different batches of particles in which different amounts of cobalt have been substituted for iron atoms.
Data is for alternating fields only.
Figure 4 shows MHE data measured for particles with the same level of cobalt doping but of different average size. Data is for alternating fields only.
Features of the present invention are more fully described in the following examples. It is to be understood that the following examples are included solely for the purposes of exemplifying the invention, and should not be understood in any way as a restriction on the broad description as set out above.
Example 1 Preparation To a solution of 7 moles NaOH and 0.04 moles NaCl03 in 6 litres of water, which is kept under argon, there is quickly added at room temperature (22°C) a solution of 2.965 moles of FeS04.7H20 and 0.035 moles of CoS04.7H20 in 3 litres of water. The precipitate of hydroxides formed contains 3 moles of metal atoms of which 1.17 atomic percent are cobalt. The suspension is heated under argon to 80°C and mixed with 1 moles of NaN03 in 0.3 litres of water. The mixture is kept at 80°C while stirring for 80 minutes and heated to the boil for at least 60 minutes.
The precipitate is washed 4 times with deionised water and vacuum dried at 100°C. The dried precipitate is oxidised by heating it under a stream of air to 280°C. After 6 hours the black precipitate is transformed into a greyish brown oxide corresponding approximately to the formula Me203, in which Me represents iron and/or cobalt.
Magnetic properties This oxide has the following magnetic values; remanence = 22emu/g, coercivity =
165 Oe. These values were measured using a Vibrating Sample Magnetometer (VSM) with a saturating field of +/-10 kOe and a magnetic field ramp rate of Oe/s. The sample for magnetic measurement was prepared by dispersing under 2% by volume of oxide powder in molten wax in a plastic sample holder of 5.4mm internal diameter by 6mm long.
Measurement of the MHE of this material as a function of applied field strength in a rotating magnetic field show that the MHE is 5.25 x 10-8 J.m/A.g when the applied field is 25kA/m and the frequency is 20kHz, a value in excess of the desired minimum of 4.5x10-8.
Comparison to existing materials Table 1 lists the maximum experimentally measured values of Magnetic Heating Efficiency for a number of commercially available materials for applied rotating magnetic fields up to 25kA/m, the maximum field that can be used in order to comply with the preferred field conditions described above. The results for the commercially available materials are compared to the oxide of Example 1 which shows the highest MHE of all.
Magnetic Material Source MHE (J.m/A.g) Co-yFe203 (S11 Bayer Chemicals 2.5 x 10-) yFe203 BASF 0.8 x 10-Magnetite Magnox 3.25 x 10-Alnico Crumax Magnetics 3.1 x 10-8 Chromium Dioxide BASF 0.25 x 10-~
Co-Fe304/Fe203 BASF < 0.5 x 10-~
Co-yFe203 (Example)Paragon Medical 5.25 x 10-Tohlo 1 It is envisaged magnetic material of the present invention microparticles may be formulated in such a way as to regulate the temperature of the tumour to some predetermined maximum. This could be achieved by incorporating ferromagnetic materials with a Curie temperature, a compensation temperature, a martensitic transformation or some other suitable magnetic transformation at the required temperature, called T~, into the microparticles. The requirement would be that a suitably large MHE is available for T < T~ and MHE ~ 0 for T > T~.
Example 2 Example Showing Effect of Particle Size, Coercivity and Loop Squareness on MHE
Figures 3 and 4 show the MHE as a function of applied field inferred from VSM
measurements on several batches of magnetic particles fabricated using the method described in the first example. These MHE results are for the case of alternating fields only.
Figure 3 shows MHE data measured for 3 different batches of particles in which the level of substitution of cobalt for iron atoms has been varied. The different levels of cobalt also give rise to different coercivities and values of loop squareness. For 1.17% cobalt the coercivity is 145 Oe (11.5 kA/m) and Poop squareness is 0.316; for 2% cobalt the coercivity is 208 Oe (16.6 kA/m) and loop squareness is 0.372; for 3.5% cobalt the coercivity is 304 Oe (24.2 kA/m) and loop squareness is 0.503. In all cases the average particle size is approximately 40 nanometers. These data show a general trend of increasing MHE with improved loop squareness.
Figure 4 shows MHE data measured for particles with the same level of cobalt doping but of different average particle size. Once again coercivity and loop squareness also varies with particle size. For the 350 nm particles coercivity is 200 Oe (15.9 kA/m) and loop squareness is 0.276; for 118 nm particles the coercivity is 241 Oe (19.2 kA/m) and loop squareness is 0.398; for 42 nm particles the coercivity is 304 (24.2 kA/m) and loop squareness is 0.503; for 32 nm particles the coercivity is 460 Oe (36.6 kA/m) and loop squareness is 0.528. Again the better the loop squareness then the better is MHE except when coercivity is too great compared to the applied field as is the case for the 32nm particles.
These examples show how the level of cobalt doping and particle physical parameters can be varied to maximise the MHE. Note that the MHE achieved by these materials up to an applied field of 25 kA/m does not reach the same level as for the material shown in example 1 for a rotating magnetic field.
It should be understood that the foregoing description of the invention including the principles, preferred embodiments and Examples cited above are illustrative of the invention and should not be regarded as being restrictive on its scope.
Variations and modifications may be made to the invention by others without departing from the spirit of that which is described as the invention and it is expressly intended that all such variations and changes which fall within this ambit are embraced thereby is intended merely to be illustrative thereof.
The ideal magnetic material is characterised by a perfectly rectangular hysteresis loop, i.e. loop squareness, defined by the ratio of the remanent to saturation magnetisation equal to 1, with coercivity of 25kA/m or less and high saturation magnetisation. Such a situation is difficult to achieve with an array of randomly aligned particles as is the case when the magnetic materials are dispersed in compositions such as cement or epoxies or in biological tissues.
Preferably, the magnetic material has a predominantly cubic magnetocrystalline anisotropy. Particles with predominantly cubic magnetocrystalline anisotropy come closest to approaching the specified behaviour in a cyclic magnetic field since they can have a hysteresis loop squareness as high as 0.86.
For a random array of particles with other types of anisotropy (e.g. uniaxial anisotropy), loop squareness will not generally exceed 0.5. In considering arrays of particles with the same coercivity but different loop squareness, the maximum value of hysteresis work per cycle (i.e. either Wa or ~V~) will occur at a higher field for the array with the lower loop squareness. This means the magnetic heating efficiency for these particles will be less than for the particles with higher loop squareness.
Having regard for the field-frequency constraint discussed above, the maximum allowable applied field strength at 20kHz is 25kA/m (314 Oe), decreasing proportionately as frequency is increased beyond 20kHz. Hence, the magnetic material desirably has a coercivity of less than 314 Oe. In addition, the remanence of the material should remain at a level that maximises the MHE.
In one embodiment of the present invention, there is provided a magnetic material having a coercivity of less than 314 Oe and a MHE of at least 4.5 x 10-$
J.m/A.g in a cyclic magnetic field where the product of the amplitude and frequency of the applied field is not more than 5 x 1 O8 A/m.s, and the frequency of the applied field is at least 20 kHz. In a preferred form of the invention the coercivity is less than 200 Oe.
The present invention should be understood to encompass any magnetic material that has the above mentioned characteristics. Preferably, the magnetic material is a substituted magnetite (Fe304) or y-ferric oxide (y-Fe203) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms. Desirably, the metal atom is a member of the group: cobalt, zinc, nickel, manganese, magnesium, copper, chromium, gallium, cadmium. In this respect the substituting metal atoms) may either be entirely selected from the same atomic species or a plurality of different metal atoms can be incorporated into the crystalline lattice.
While it will be appreciated that any of the above mentioned metal atoms may be substituted for iron atoms in the magnetite (Fe304) or y-ferric oxide (y-Fe203) crystalline lattice, the magnetic material must be possessed of a predominantly cubic magnetocrystalline anisotropy. Preferably, the substituting metal atoms are dispersed in a substantially even manner throughout the crystalline lattice.
When dispersed in such a manner the magnetic material tends to have a more predictable heating efficiency compared to the situation where the substituting metal atoms are all located in one region of the crystalline lattice.
In a highly specific form of the invention, the alternate metal atoms are cobalt atoms, and the magnetic material is a substituted magnetite (Fe304) or y-ferric oxide (y-Fe203) crystalline lattice. Where cobalt is the substituting metal atom the degree of substitution is preferably less than about 4% of the iron atoms in the crystalline lattice, more preferably in the range 0.2 and 3.5%.
In addition to being substituted preferably the magnetic material is provided in particulate form, with particles possessing equant morphology, such as simple cubic or spherical shapes, and being of a size between 20nm and 1 Vim.
To the extent that the present invention is to be used in the treatment of diseased tissue, there are several undesirable physiological effects that occur in response to sufficiently high rate of change of magnetic field, or d8/dt. These effectively impose limits on the frequency and strength of the magnetic field used in this application. These physiological responses are (i) cardiac muscle stimulation, (ii) peripheral nerve stimulation, and (iii) tissue heating due to eddy current generation.
To avoid cardiac muscle stimulation the frequency applied in the cyclic magnetic field should be greater than lOkHz. Preferably, a frequency limit of 20kHz is imposed to stay above the audible range, an important consideration for patient and operator comfort. Operating above 20kHz is highly desirable since this frequency is above the audible range and so patient and operator comfort is substantially improved over that at lower frequencies where the noise may be at an uncomfortable level.
In addition to the above where the present invention is used in hyperthermic treatment of cancer, the MHE of that material is preferably such as to enable production of sufficient heat to raise the temperature of the cancerous tissue to 42°C, being the minimum temperature required for therapeutic effect.
The scenario that demands the highest MHE from the magnetic material is likely to be the one where the magnetic material is delivered in the form of microcapsules to the site of the cancer via intra-arterial infusion.
The relatively small number of microcapsules that can be delivered via intra-arterial infusion means that each particle should be adapted to produce more heat in order to obtain the same therapeutic benefit. Preferably the magnetic material is to be capable of producing a minimum of 22.5 Watts per gram of material when exposed to the cyclic magnetic field.
Advantages gained by using a magnetic material within the scope of the present invention include:
1 ) improved therapeutic effectiveness by virtue of the fact that higher tumour temperatures can be reached more quickly (the effectiveness of hyperthermia therapy improves markedly as temperature is increased beyond 42°C);
2) reduced toxic side effects because:
_7_ i/. less microcapsules need to be used to achieve therapeutic heating in tumours (advantageous if the microcapsules have any intrinsic toxicity), ii/. more rapid heating of the tumour may be achieved which implicates less of the healthy tumour tissue immediately surrounding the tumour (the longer time required to heat the tumour the more the immediately surrounding tissue will be heated by thermal conduction);
3) increased likelihood of successful treatment especially for tumours that would otherwise be expected to only receive a marginal benefit;
4) the techniques have a wider applicability for the treatment of different types of cancer;
5) using reduced field strengths eases engineering difficulties associated with machine design;
In another embodiment there is provided a method for the production of a magnetic material within the scope of the present invention, the method comprising the steps of:
(i) dissolving a water-soluble salt of iron and one or more water-soluble salts of one or more alternate metal ions in aqueous solution;
(ii) co-precipitating hydroxides of iron and cobalt or each alternate metal ion from this solution;
(iii) treating the co-precipitated hydroxides in an aqueous medium with an oxidising agent which transforms the hydroxides into ferromagnetic iron oxides containing cobalt or each alternate metal ion;
(iv) separating the oxides from the aqueous medium, then drying and heating the oxides in an oxidising gaseous medium to a temperature not surpassing 500°C.
The oxide may be dried in a gaseous oxidising medium at a temperature between about 200-350°C. Alternatively, the oxides are heated in a gaseous oxidising medium to approximately 400°C before being slowly cooled to room temperature WO 00/52714 PC'~/AU00/00151 _g_ while being rotated in a magnetic field. Typically, the magnetic field has a rotational frequency of about 60 r.p.m. and a field strength of about 3 kOe.
In one form of the invention, the hydroxides are precipitated in conditions which cause the precipitated hydroxides to contain 1-20 atomic percent of iron in the trivalent form, the remainder being in divalent form. In a more specific form of the invention, the hydroxides are precipitated in conditions which cause the precipitated hydroxides to contain 5-15 atomic percent of iron in the trivalent form, the remainder being in divalent form.
The water-soluble salt of iron used in the preparation of the aqueous solution may be organic or inorganic. For example, the water-soluble salt of iron used in the preparation of the aqueous solution may be iron sulphate.
The water-soluble salt of cobalt or each alternate metal ion used in the preparation of the aqueous solution may also be organic or inorganic. Where the further alternate ion is cobalt, the water-soluble salt may be cobalt sulphate.
The co-precipitation of the hydroxides may be induced by the addition of an alkaline agent such as an alkali or alkaline earth metal hydroxide.
Typically, the co-precipitation of hydroxides is carried out at 5-30°C.
Suitable oxidising agents include nitrates, such as potassium-, sodium-, ammonium-nitrate, water soluble chlorates, such as sodium chlorate, persulfates such as sodium persulfate, H202 and oxygen.
The oxidation of the co-precipitated hydroxides is advantageously carried out at temperatures between about 50°C and the boiling point of the solution.
In a specific form of the invention, oxidation of the co-precipitated hydroxides takes place at temperatures of about 65-90°C.
In a further embodiment there is provided a method for production of a magnetic material within the scope of the invention, the method comprising the steps of:
(i) Procurement of non-magnetic cubic precursor particles;
-g_ (ii) Coating of the non-magnetic cubic precursor particles to prevent sintering of the particles;
(iii) Reduction of the non-magnetic cubic precursor particles to magnetite; and (iv) Oxidization of magnetite to y-ferric oxide (y-Fe203).
An example of a non-magnetic cubic precursor particles is haematite particles.
Methods for Precipitation of Haematite Precursors 1. In a first method for precipitation of uniform a-Fe203 particles, a dilute solution of an iron(III) salt was heated at reflux in dilute acid for at least 24 hours. The iron(III) salt used was the chloride salt. Nitrate or perchlorate salt can also be used. The corresponding acid used was hydrochloric acid. However nitric or perchloric acid are also appropriate. 0.4 mol/L FeCl3 (l0ml), 0.032 mol/L HCI
(25m1) and D.I. water (365 ml) were preheated to 100 deg. C, then mixed and maintained at reflux for 48 hours. The resulting precipitate was collected by centrifugation and washed by repeated centrifugation/re-suspension cycles in D.I. water, or by dialysis with D.I. water for a period of days.
2. In a second method for precipitation of uniform a-Fe203 particles, a concentrated iron(III) hydroxide gel was aged for a period of days at 100 deg.
C. The hydroxide gel was formed by mixing an equivalent amount of a strong base, being sodium hydroxide with a solution of an iron(III) salt. Potassium hydroxide is another strong base which can also be used for mixing with a solution of an iron (III) salt. 6.0 mol/L NaOH solution (65m1) was slowly added to a stirred solution of 2.OM FeCl3 (65 ml) in a 125m1 Erlenmeyer flask. The flask was then sealed and placed in an oven, preheated to 100°C, for 24 hours. The resulting precipitate was collected by centrifugation and washed by repeated centrifugation/re-suspension cycles in D.I. water, or by dialysis with D.I. water for a period of days.
Surface Treatment and Drying In order to prevent sintering of non-magnetic cubic precursor particles during reduction, the particles can be coated with a surfactant such as oleic acid, stearic acid or other long-chain carboxylic acids. Other anionic surfactants such as sodium dodecyl benzene sulphonate (SDBS) may also be used.
Method for Surface Treatment and Drying A haematite suspension (100m1) containing about 0.25g a-Fe203 was warmed to about 60 deg. C with stirring and rendered basic (~pH 11 ) by addition of a little NaOH solution (1 mol/L). A 1 % (w/w) solution of sodium stearate (5 ml) was added and the suspension stirred and heated gently for a further 15 minutes.
The mixture was then acidified by addition of HCI and transferred to a separating funnel and when cool, the stearate-coated a-Fe203 is extracted into 130 ml hexane. After washing excess stearic acid from the organic phase with a few aliquots of D.I. water, the hexane phase is evaporated to dryness at 50-70°C
under reduced pressure.
Reduction of Haematite to Magnetite Non-magnetic cubic precursor particles such as a-Fe203 may be converted to magnetic Fe304 by heat treatment in a reducing gas such as hydrogen or carbon monoxide. The reduction may be carried out at temperatures between 350 and 450°C and at gas flow rates of 100m1/min or greater. Ideally the reduction is carried out in an atmosphere of 5% hydrogen and 95% nitrogen at a temperature of 400°C over a period of at least 1 hour.
Oxidation of Magnetite Oxidation of magnetite to y-Fe203 is carried out by heat treatment in an oxidising gaseous medium. The magnetite may be dried in a gaseous oxidising medium at a temperature between about 200-350°C. Alternatively, the magnetite is heated in a gaseous oxidising medium to approximately 400°C before being slowly cooled to room temperature while being rotated in a magnetic field. Typically, the magnetic field has a rotational frequency of about 60 rpm and a field strength of about 3kOe.
The present invention further provides an improved method for site specific treatment of diseased tissue in a patient, which comprises the steps of:
(i) delivering the magnetic material of the present invention to diseased tissue in a patient; and (ii) exposing the magnetic material in the patient to a cyclic magnetic field with a frequency of greater than about 20kHz and a field strength selected such that the product of field strength, frequency and the radius of the exposed region is less than about 7.5 x 10' A/s to generate hysteresis heat in the diseased tissue.
Preferably, step (ii) is carried out for sufficient time to generate enough heat from the administered magnetic material to raise the tumour temperature above about 42 ° C. It will be appreciated that the amount of time for treating a tumour will largely depend on the size, position and physical structure of the tumour.
Most preferably step (ii) is repeated until the diseased tissue has been destroyed or treated sufficiently to ameliorate the disease.
The method of the invention provides a means to increase temperature in the area of diseased tissue to above 41 °C to decrease the viability of malignant cells.
A decrease in the viability of malignant cells results in either cell death or increased cell sensitivity to the effects of ionising radiation or chemotherapeutic drugs.
During treatment, patients are placed into a machine that generates a cyclic magnetic field. The cyclic magnetic field could be, for example, either a linear alternating magnetic field or a rotating magnetic field of strength H and frequency f.
In a linear alternating magnetic field the amplitude of the field varies sinusoidally along a fixed directional axis between a maximum positive amplitude and a maximum negative amplitude at a frequency of f. The magnetic field strength as a function of time, Ha(t), is described mathematically by Halt) = HaSin(2rctt) (1 ) where Ha is the magnetic field amplitude.
A rotational magnetic field can be described mathematically as the superposition of two orthogonal linear alternatirig magnetic fields with a n/2 phase difference, i.e.
Hr(t) = H,~Sin(2rdt) + HYSin(2rc~t+~r12) (2) where HX and Hy are the amplitudes of linear alternating magnetic fields directed in the X and Y directions respectively which combine to give Hr and f is their frequency of alternation. In this case the amplitude of the field remains constant but the direction of the field rotates with angular frequency of 2r~f. An advantage of the use of a rotational magnetic field compared to a linear alternating magnetic field of the same frequency and amplitude is that it leads to higher magnetic heating efficiency of the magnetic materials under some conditions. This in turn means that lower frequency and field strengths can be used in the method, if desired.
In order that enough hysteresis heat is generated by the magnetic material the cyclic magnetic field used in the method desirably has a relatively high frequency.
The higher the frequency the greater the rate of heating in the tissues that contain the magnetic material. However, the physiological response to high amplitude, high frequency magnetic fields limit the field amplitude and frequency that can be used in any clinical application. These limitations result from nerve muscle activation and eddy current heating which depends, inter alia, on the electrical conductivity of the tissue. Both of these are as a result of the electric fields induced in the tissue by the magnetic field.
3 _ Preferably, the magnetic material is mixed in a liquid emulsion or is formed -into microcapsules which may then be mixed with a suitable biocompatible medium for delivery into a patient. Most preferably the magnetic material is bound in a matrix material to form a microcapsule. Most magnetic particles themselves are, typically, too small and too dense to enable optimum delivery to the site of diseased tissue. Therefore, they are desirably encapsulated in microcapsules.
Important properties of microcapsules are their density and their diameter.
The density affects the efficiency of their carriage by the blood stream to the site of immobilisation in the diseased tissues vascular network while the size determines the proximity of the point of immobilisation to the diseased tissue.
Preferably, the magnetic material is bound in a matrix material which does not adversely affect the hysteresis or eddy current heating properties of the magnetic particles. The non-toxic binder or matrix material may comprise any of the suitable non-toxic materials which are well known in the microencapsulation art.
Suitable materials include, for example, proteins, polymeric resins such as styrene-divinylbenzene, biopol, albumin, chitosan etc.
In a preferred form of the invention, the microcapsules are adapted to bind or absorb or contain a cytotoxic material which is released upon heating of the microcapsule. For example the microcapsule may be composed of a porous, heat sensitive material which is non-toxic to and, preferably, inert to or compatible with animal tissue and which has embedded within it suitable magnetic material. The pores in the material are desirably filled with the cytotoxic compound. Upon hysteresis heating the micro-particles are capable of expanding, thereby permitting the release of the cytotoxic compound. Such particles should, however, be resistant to melting upon hysteresis heating. Thus, the use of such particles in the method of the present invention provides a single device with which combined chemotherapy and thermotherapy can be achieved to treat diseased tissue in a patient.
Another alternative delivery technique could be the injection or intra-vascular infusion of a suitable ferrocolloid which could consist, for example, of a suspension of magnetic microparticles in a liquid medium such as lipiodol. In this case the magnetic particles could range in size from subdomain nanometer size up to several microns.
A combination of different types of microcapsules may also be administered at the time of treatment to provide a multimode treatment. Microcapsules may be either radioactive microcapsules or chemotherapeutic microcapsules together with the hyperthermic microcapsules described. Further, the targeted hyperthermia therapy may be used in conjunction with conventional radiotherapy and/or chemotherapy. The choice of treatments will depend upon the specific details of each case as it presents.
According to a further embodiment of the invention, an ionising radiation source may be applied to the locus of the diseased tissue in conjunction with a magnetic field, said tissue having microcapsules as herein described included therein.
The radiation source may be microcapsules which contain a radioactive compound such as Yttrium-90 or delivered from an external radiation source.
An additional application of magnetic materials with the properties described in this application would be for use in antipilferage devices, or Electronic Article Surveillance (EAS) devices. Here, a magnetically very soft material is combined with a semi-hard material to make a label or tag that can be attached to an article in, say, a shop or library. If an attempt is made to move the article through a detection gate without first deactivating the tag then an alarm is sounded.
The tags are deactivated by magnetising the semi-hard material using a deactivator tablet that contains strong permanent magnets. The semi-hard magnetic material may also be used to provide a permanent bias field for the soft component. The magnetic characteristics of the magnetic materials described in this patent application make them well suited for use as the semi-hard component of the antipilferage devices.
BEST MODES) FOR CARRYING OUT THE INVENTION
In the drawings:
Figure 1 illustrates a typical form of alternating hysteresis work per cycle, Wa, as a function of applied field, Ha.
Figure 2 illustrates a typical form of rotational hysteresis work per cycle, W,, as a function of applied field, H~.
Figure 3 shows MHE data measured for 3 different batches of particles in which different amounts of cobalt have been substituted for iron atoms.
Data is for alternating fields only.
Figure 4 shows MHE data measured for particles with the same level of cobalt doping but of different average size. Data is for alternating fields only.
Features of the present invention are more fully described in the following examples. It is to be understood that the following examples are included solely for the purposes of exemplifying the invention, and should not be understood in any way as a restriction on the broad description as set out above.
Example 1 Preparation To a solution of 7 moles NaOH and 0.04 moles NaCl03 in 6 litres of water, which is kept under argon, there is quickly added at room temperature (22°C) a solution of 2.965 moles of FeS04.7H20 and 0.035 moles of CoS04.7H20 in 3 litres of water. The precipitate of hydroxides formed contains 3 moles of metal atoms of which 1.17 atomic percent are cobalt. The suspension is heated under argon to 80°C and mixed with 1 moles of NaN03 in 0.3 litres of water. The mixture is kept at 80°C while stirring for 80 minutes and heated to the boil for at least 60 minutes.
The precipitate is washed 4 times with deionised water and vacuum dried at 100°C. The dried precipitate is oxidised by heating it under a stream of air to 280°C. After 6 hours the black precipitate is transformed into a greyish brown oxide corresponding approximately to the formula Me203, in which Me represents iron and/or cobalt.
Magnetic properties This oxide has the following magnetic values; remanence = 22emu/g, coercivity =
165 Oe. These values were measured using a Vibrating Sample Magnetometer (VSM) with a saturating field of +/-10 kOe and a magnetic field ramp rate of Oe/s. The sample for magnetic measurement was prepared by dispersing under 2% by volume of oxide powder in molten wax in a plastic sample holder of 5.4mm internal diameter by 6mm long.
Measurement of the MHE of this material as a function of applied field strength in a rotating magnetic field show that the MHE is 5.25 x 10-8 J.m/A.g when the applied field is 25kA/m and the frequency is 20kHz, a value in excess of the desired minimum of 4.5x10-8.
Comparison to existing materials Table 1 lists the maximum experimentally measured values of Magnetic Heating Efficiency for a number of commercially available materials for applied rotating magnetic fields up to 25kA/m, the maximum field that can be used in order to comply with the preferred field conditions described above. The results for the commercially available materials are compared to the oxide of Example 1 which shows the highest MHE of all.
Magnetic Material Source MHE (J.m/A.g) Co-yFe203 (S11 Bayer Chemicals 2.5 x 10-) yFe203 BASF 0.8 x 10-Magnetite Magnox 3.25 x 10-Alnico Crumax Magnetics 3.1 x 10-8 Chromium Dioxide BASF 0.25 x 10-~
Co-Fe304/Fe203 BASF < 0.5 x 10-~
Co-yFe203 (Example)Paragon Medical 5.25 x 10-Tohlo 1 It is envisaged magnetic material of the present invention microparticles may be formulated in such a way as to regulate the temperature of the tumour to some predetermined maximum. This could be achieved by incorporating ferromagnetic materials with a Curie temperature, a compensation temperature, a martensitic transformation or some other suitable magnetic transformation at the required temperature, called T~, into the microparticles. The requirement would be that a suitably large MHE is available for T < T~ and MHE ~ 0 for T > T~.
Example 2 Example Showing Effect of Particle Size, Coercivity and Loop Squareness on MHE
Figures 3 and 4 show the MHE as a function of applied field inferred from VSM
measurements on several batches of magnetic particles fabricated using the method described in the first example. These MHE results are for the case of alternating fields only.
Figure 3 shows MHE data measured for 3 different batches of particles in which the level of substitution of cobalt for iron atoms has been varied. The different levels of cobalt also give rise to different coercivities and values of loop squareness. For 1.17% cobalt the coercivity is 145 Oe (11.5 kA/m) and Poop squareness is 0.316; for 2% cobalt the coercivity is 208 Oe (16.6 kA/m) and loop squareness is 0.372; for 3.5% cobalt the coercivity is 304 Oe (24.2 kA/m) and loop squareness is 0.503. In all cases the average particle size is approximately 40 nanometers. These data show a general trend of increasing MHE with improved loop squareness.
Figure 4 shows MHE data measured for particles with the same level of cobalt doping but of different average particle size. Once again coercivity and loop squareness also varies with particle size. For the 350 nm particles coercivity is 200 Oe (15.9 kA/m) and loop squareness is 0.276; for 118 nm particles the coercivity is 241 Oe (19.2 kA/m) and loop squareness is 0.398; for 42 nm particles the coercivity is 304 (24.2 kA/m) and loop squareness is 0.503; for 32 nm particles the coercivity is 460 Oe (36.6 kA/m) and loop squareness is 0.528. Again the better the loop squareness then the better is MHE except when coercivity is too great compared to the applied field as is the case for the 32nm particles.
These examples show how the level of cobalt doping and particle physical parameters can be varied to maximise the MHE. Note that the MHE achieved by these materials up to an applied field of 25 kA/m does not reach the same level as for the material shown in example 1 for a rotating magnetic field.
It should be understood that the foregoing description of the invention including the principles, preferred embodiments and Examples cited above are illustrative of the invention and should not be regarded as being restrictive on its scope.
Variations and modifications may be made to the invention by others without departing from the spirit of that which is described as the invention and it is expressly intended that all such variations and changes which fall within this ambit are embraced thereby is intended merely to be illustrative thereof.
Claims (37)
1. A magnetic material having a magnetic heating efficiency of at least 4.5 x 10-8 J.m/A.g in a cyclic magnetic field where the product of the amplitude and frequency of the applied field is less than or equal to 5 x 8 A/m.s, and the frequency of the applied field is at least 20kHz and wherein (i) the magnetic material is a substituted magnetite (Fe3O4) or gamma ferric oxide (.gamma.-Fe2O3) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms and (ii) the magnetic material has a predominantly cubic magnetocrystalline anisotropy.
2. A magnetic material according to claim 1 wherein the magnetic material is provided in particulate form, with particles possessing equant morphology.
3. A magnetic material according to any one of claim 2 wherein the particles are of a size between 20nm and µ Vim.
4. A magnetic material according to claim 2 characterised by loop squareness of between 0.5 and 1 with coercivity of 25 kA/m or less and high saturation magnetism.
5. A magnetic material according to any one of the preceding claims wherein the magnetic material has a coercivity of less than 314 Oe.
6. A magnetic material according to claim 5 wherein the coercivity is less than 200 Oe.
7. A magnetic material according to any one of the preceding claims wherein the substituting metal atoms are selected from a group consisting of cobalt, zinc, nickel, manganese, magnesium, copper, chromium, gallium and cadmium.
8. A magnetic material according to claim 7 wherein the substituting metal atoms may either be selected entirely from the same atomic species or a plurality of different metal atoms can be incorporated into the crystalline lattice.
9.A magnetic material according to any one of claims 7 or 8 wherein the substituting metal atoms are dispersed in a substantially even manner throughout the crystalline lattice.
10.A magnetic material according to any one of claims 7 to 9 wherein the substituting metal atom is cobalt.
11.A magnetic material according to claim 10 wherein the degree of substitution with cobalt atoms is less than about 4% of the iron atoms in the crystalline lattice.
12.A magnetic material according to claim 11 wherein the degree of substitution with cobalt atoms is in the range of 0.2 and 3.5% of the iron atoms in the crystalline lattice.
13.A magnetic material according to any one of the preceding claims wherein the magnetic heating efficiency of that material is such as to enable production of sufficient heat to raise the temperature of the surrounding matter to 42°C.
14.A magnetic material according to claim 13 wherein the magnetic material is capable of producing at least 22.5 watts per gram of material when exposed to a cyclic magnetic field.
15.A microcapsule comprising a magnetic material according to any one of the preceding claims wherein the magnetic material is bound in a matrix material.
16.A microcapsule according to claim 15 wherein the magnetic material is bound in a matrix material which does not adversely affect the hysteresis or eddy current heating properties of the magnetic particles.
17.A microcapsule according to claim 15 wherein the matrix material is selected from a group comprising proteins, polymeric resins such as styrene-divinyl benzene, biopol, albumin and chitosan.
18.A microcapsule according to claim 15 wherein the microcapsules are adapted to bind or absorb or contain a cytotoxic material.
19.A microcapsule according to claim 15 wherein the microcapsule is composed of a porous, heat sensitive material which is non-toxic and inert to or compatible with animal tissue and which has embedded within it suitable magnetic material.
20.A microcapsule according to claim 15 wherein the pores within the porous material are filled with a cytotoxic material.
21.A microcapsule according to claim 18 or 20 wherein the cytotoxic material is released upon heating of the microcapsule.
22.A composition comprising (i) a magnetic material according to anyone of claims 1 to 14 or a microcapsule according to anyone of claims 15 to 21 and (ii) at least a microcapsule suspension selected from the group consisting of radioactive microcapsules or chemotherapeutic microcapsules.
23.A composition according to claim 22 wherein the radioactive microcapsules at least contain Yttrium-90 as the radiation source.
24.A composition comprising a magnetic material according to anyone of claim 1 to 14 in a liquid medium suspension.
25.A composition according to anyone of claim 22 to 24 wherein the liquid medium is lipiodol.
26.A method for site specific treatment of diseased tissue in a patient, which comprises the steps of:
(i) delivering the magnetic material of anyone of claims 1 to 14 or the microcapsule according to anyone of claims 15 to 21 or the composition according to anyone of claims 22 to 25 to the diseased tissue in a patient; and (ii) exposing the magnetic material in the patient to a cyclic magnetic field with a frequency of about 20 kHz and a field strength selected such that the product of field strength, frequency and the radius of the exposed region is less than about 7.5 x 10 7 A/s to generate hysteresis heat in the diseased tissue wherein the magnetic material is a substituted magnetite (Fe3O4) or gamma ferric oxide (.gamma.-Fe2O3) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms and (ii) the magnetic material has a predominantly cubic magnetocrystalline anisotropy.
(i) delivering the magnetic material of anyone of claims 1 to 14 or the microcapsule according to anyone of claims 15 to 21 or the composition according to anyone of claims 22 to 25 to the diseased tissue in a patient; and (ii) exposing the magnetic material in the patient to a cyclic magnetic field with a frequency of about 20 kHz and a field strength selected such that the product of field strength, frequency and the radius of the exposed region is less than about 7.5 x 10 7 A/s to generate hysteresis heat in the diseased tissue wherein the magnetic material is a substituted magnetite (Fe3O4) or gamma ferric oxide (.gamma.-Fe2O3) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms and (ii) the magnetic material has a predominantly cubic magnetocrystalline anisotropy.
27.A method for site specific treatment of diseased tissue in a patient according to claim 26 wherein the magnetic material is provided in particulate form, with particles possessing equant morphology.
28.A method for site specific treatment of diseased tissue in a patient according to claim 26 wherein step (ii) is carried out for sufficient time to generate enough heat from the administered magnetic material to raise the diseased tissue temperature above about 42°C.
29.A method for site specific treatment of diseased tissue in a patient according to any one of claims 26 to 28 wherein step (ii) is repeated until the diseased tissue has been destroyed or treated sufficiently to ameliorate the disease.
30. A method for specific treatment of diseased tissue in a patient according to any one of claims 26 to 29 wherein the cyclic magnetic field is a linear alternating magnetic field of strength H and frequency f.
31. A method for specific treatment of diseased tissue in a patient according to any one of claims 26 to 29 wherein the cyclic magnetic field is a rotating magnetic field of strength H and frequency f.
32. A method for site specific treatment of diseased tissue in a patient according to any one of claims 26 to 31 wherein an ionising radiation source is applied to the locus of the diseased tissue in conjunction with a magnetic field.
33. A method for site specific treatment of diseased tissue according to claim 30 or claim 31 wherein the radiation source may be microcapsules which contain a radioactive compound such as Yttrium-90 or delivered from an external radiation source.
34. A magnetic material according to claim 13 wherein the magnetic material is delivered in the form of microcapsules to the site of cancer via intra-arterial infusion.
35. A method of production of a magnetic material as substantially described in Example 1.
36. A magnetic material according to claim 1 and as substantially herein described in Example 2.
37. An antipilferage device comprising a magnetic material according to any one of claims 1 to 14 or a microcapsule according to claims 15 to 21 or a composition according to claims 22 to 25.
Applications Claiming Priority (3)
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AUPP8998 | 1999-03-03 | ||
AUPP8998A AUPP899899A0 (en) | 1999-03-03 | 1999-03-03 | Magnetic material |
PCT/AU2000/000151 WO2000052714A1 (en) | 1999-03-03 | 2000-03-03 | Heating of magnetic material by hysteresis effects |
Publications (1)
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CA2365403A1 true CA2365403A1 (en) | 2000-09-08 |
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CA002365403A Abandoned CA2365403A1 (en) | 1999-03-03 | 2000-03-03 | Heating of magnetic material by hysteresis effects |
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US (1) | US6599234B1 (en) |
EP (1) | EP1166291A4 (en) |
JP (1) | JP4949556B2 (en) |
AU (1) | AUPP899899A0 (en) |
CA (1) | CA2365403A1 (en) |
WO (1) | WO2000052714A1 (en) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7731648B2 (en) | 2001-07-25 | 2010-06-08 | Aduro Biotech | Magnetic nanoscale particle compositions, and therapeutic methods related thereto |
US6997863B2 (en) | 2001-07-25 | 2006-02-14 | Triton Biosystems, Inc. | Thermotherapy via targeted delivery of nanoscale magnetic particles |
US7951061B2 (en) | 2001-07-25 | 2011-05-31 | Allan Foreman | Devices for targeted delivery of thermotherapy, and methods related thereto |
US7074175B2 (en) | 2001-07-25 | 2006-07-11 | Erik Schroeder Handy | Thermotherapy via targeted delivery of nanoscale magnetic particles |
DE10238853A1 (en) * | 2002-08-24 | 2004-03-04 | Philips Intellectual Property & Standards Gmbh | Process for local heating with magnetic particles |
KR101201657B1 (en) | 2003-01-31 | 2012-11-14 | 가부시키 가이샤 오오쯔카 세이야쿠 고우죠우 | Auxiliary agent to be used in cancer therapy by dielectric heating and cancer therapy method |
WO2004093889A1 (en) * | 2003-03-28 | 2004-11-04 | Kansai Technology Licensing Organization Co., Ltd. | Method for preparing therapeutic agent for cancer |
EP1615553B1 (en) * | 2003-04-15 | 2017-01-18 | Philips Intellectual Property & Standards GmbH | Arrangement for influencing magnetic particles |
US8133256B2 (en) | 2003-10-02 | 2012-03-13 | Lawrence Livermore National Security, Llc | Shape memory polymer foams for endovascular therapies |
US20070135907A1 (en) | 2003-10-02 | 2007-06-14 | The Regents Of The University Of California | Stent with expandable foam |
US7591834B2 (en) * | 2004-03-26 | 2009-09-22 | Lawrence Livermore National Security, Llc | Shape memory system with integrated actuation using embedded particles |
US7627381B2 (en) * | 2004-05-07 | 2009-12-01 | Therm Med, Llc | Systems and methods for combined RF-induced hyperthermia and radioimmunotherapy |
US20070135913A1 (en) * | 2004-06-29 | 2007-06-14 | Micardia Corporation | Adjustable annuloplasty ring activation system |
US20080183285A1 (en) * | 2004-06-29 | 2008-07-31 | Micardia Corporation | Adjustable cardiac valve implant with selective dimensional adjustment |
US7396364B2 (en) | 2004-06-29 | 2008-07-08 | Micardia Corporation | Cardiac valve implant with energy absorbing material |
US20060015178A1 (en) * | 2004-07-15 | 2006-01-19 | Shahram Moaddeb | Implants and methods for reshaping heart valves |
US20070055368A1 (en) * | 2005-09-07 | 2007-03-08 | Richard Rhee | Slotted annuloplasty ring |
WO2007035871A1 (en) * | 2005-09-21 | 2007-03-29 | Massachusetts Institute Of Technology | Systems and methods for tuning properties of nanoparticles |
US20070142907A1 (en) * | 2005-12-16 | 2007-06-21 | Micardia Corporation | Adjustable prosthetic valve implant |
US7536228B2 (en) | 2006-03-24 | 2009-05-19 | Micardia Corporation | Activation device for dynamic ring manipulation |
ATE551703T1 (en) | 2006-05-08 | 2012-04-15 | Iner Aec Executive Yuan | LIPIODOL MAGNETIC COMPONENT AND ASSOCIATED MANUFACTURING METHOD |
US20080228272A1 (en) * | 2006-12-04 | 2008-09-18 | Micardia Corporation | Dynamically adjustable suture and chordae tendinae |
US20100106181A1 (en) * | 2007-01-08 | 2010-04-29 | Yossi Gross | In-situ filter |
EP2242539B1 (en) * | 2008-01-16 | 2015-04-01 | Nanospectra Biosciences, Inc. | Nanoparticles for focused hyperthermia to increase efficacy of radiation therapy |
GB0811856D0 (en) * | 2008-06-27 | 2008-07-30 | Ucl Business Plc | Magnetic microbubbles, methods of preparing them and their uses |
KR101613635B1 (en) * | 2008-10-31 | 2016-04-20 | 삼성전자주식회사 | Microcapsule, structure comprising same, article comprising same, and method for preparing same |
US8565892B2 (en) | 2009-10-31 | 2013-10-22 | Qteris, Inc. | Nanoparticle-sized magnetic absorption enhancers having three-dimensional geometries adapted for improved diagnostics and hyperthermic treatment |
KR101691154B1 (en) * | 2010-03-05 | 2017-01-02 | 삼성전자주식회사 | Microcapsule array substrate, apparatus for transferring smell information having the substrate, and electronic device having the apparatus |
US9005151B2 (en) | 2011-09-07 | 2015-04-14 | Choon Kee Lee | Thermal apparatus |
KR101560441B1 (en) * | 2013-01-25 | 2015-10-14 | 주식회사 엘지화학 | Method for fabricating the iron oxide nanoparticles |
KR20190029680A (en) | 2016-07-14 | 2019-03-20 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | METHODS, DEVICES AND SYSTEMS FOR INDUCTION HEATING OF EXTERNAL METAL IMPLANT |
CN114601976A (en) | 2017-03-14 | 2022-06-10 | 形状记忆医疗公司 | Shape memory polymer foam to seal the space around a valve |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB895179A (en) | 1959-06-12 | 1962-05-02 | Bayer Ag | Acicular cobalt-containing ª+-ferric oxide |
US4303636A (en) | 1974-08-20 | 1981-12-01 | Gordon Robert T | Cancer treatment |
US4106488A (en) | 1974-08-20 | 1978-08-15 | Robert Thomas Gordon | Cancer treatment method |
US4323056A (en) * | 1980-05-19 | 1982-04-06 | Corning Glass Works | Radio frequency induced hyperthermia for tumor therapy |
FR2508802A1 (en) | 1981-07-03 | 1983-01-07 | Thomson Csf | Magnetic powders for use in hyperthermic treatments - e.g. of tumours, heated by hysteresis in alternating magnetic field |
US4574782A (en) | 1981-11-16 | 1986-03-11 | Corning Glass Works | Radio frequency-induced hyperthermia for tumor therapy |
US4545368A (en) | 1983-04-13 | 1985-10-08 | Rand Robert W | Induction heating method for use in causing necrosis of neoplasm |
US4662359A (en) | 1983-08-12 | 1987-05-05 | Robert T. Gordon | Use of magnetic susceptibility probes in the treatment of cancer |
US4983159A (en) | 1985-03-25 | 1991-01-08 | Rand Robert W | Inductive heating process for use in causing necrosis of neoplasms at selective frequencies |
DE3619746A1 (en) | 1986-06-12 | 1987-12-17 | Basf Ag | SUPER PARAMAGNETIC SOLID PARTICLES |
JPH0288059A (en) * | 1988-09-26 | 1990-03-28 | Univ Kyoto | Ceramic heat generating substance for hot heat curing and manufacture thereof |
US5197940A (en) | 1990-01-29 | 1993-03-30 | Hypertherm Corp. | Local application tumor treatment apparatus |
US5236410A (en) | 1990-08-02 | 1993-08-17 | Ferrotherm International, Inc. | Tumor treatment method |
US5181021A (en) | 1991-01-14 | 1993-01-19 | Eastman Kodak Co. | Responder target for theft detection apparatus |
JPH06254168A (en) | 1991-10-29 | 1994-09-13 | Tanaka Kikinzoku Kogyo Kk | Inside-tissue heating/warming therapy |
US5411730A (en) | 1993-07-20 | 1995-05-02 | Research Corporation Technologies, Inc. | Magnetic microparticles |
US5429583A (en) | 1993-12-09 | 1995-07-04 | Pegasus Medical Technologies, Inc. | Cobalt palladium seeds for thermal treatment of tumors |
DE19600744A1 (en) | 1996-01-11 | 1997-07-17 | Werner Alois Prof Dipl Kaiser | Magnetic substance for local hyperthermic treatment of mainly small tumors |
AU2627797A (en) | 1996-05-10 | 1997-12-05 | Paragon Medical Limited | Targeted hysteresis hyperthermia as a method for treating diseased tissue |
AUPN978296A0 (en) | 1996-05-10 | 1996-05-30 | Gray, Bruce N | Targeted hysteresis hyperthermia as a method for treating cancer |
AUPP008197A0 (en) | 1997-10-29 | 1997-11-20 | Paragon Medical Limited | Improved targeted hysteresis hyperthermia as a method for treating diseased tissue |
-
1999
- 1999-03-03 AU AUPP8998A patent/AUPP899899A0/en not_active Abandoned
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- 2000-03-03 WO PCT/AU2000/000151 patent/WO2000052714A1/en active Application Filing
- 2000-03-03 US US09/914,714 patent/US6599234B1/en not_active Expired - Lifetime
- 2000-03-03 CA CA002365403A patent/CA2365403A1/en not_active Abandoned
- 2000-03-03 EP EP00907340A patent/EP1166291A4/en not_active Withdrawn
- 2000-03-03 JP JP2000603053A patent/JP4949556B2/en not_active Expired - Fee Related
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US6599234B1 (en) | 2003-07-29 |
AUPP899899A0 (en) | 1999-03-25 |
JP2002538616A (en) | 2002-11-12 |
EP1166291A4 (en) | 2002-09-11 |
JP4949556B2 (en) | 2012-06-13 |
EP1166291A1 (en) | 2002-01-02 |
WO2000052714A1 (en) | 2000-09-08 |
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