JP2014094838A - Method of manufacturing strong magnetic iron oxide particles - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of manufacturing strong magnetic iron oxide particles and the like having excellent heat generation characteristics, excellent in dispersion stability of media for injection, and suitable for cancer cautery treatment.SOLUTION: A method includes dispersing iron hydroxide particles and/or hematite particles into polyhydric alcohol and heat treatment. Strong magnetic iron oxide particles can be obtained by using reducing power of the polyhydric alcohol according to the invention.

Description

  The present invention relates to a method for producing ferromagnetic iron oxide particles. More specifically, the present invention relates to a method for producing ferromagnetic iron oxide particles and the like suitable for cancer ablation treatment having excellent heat generation characteristics and excellent dispersion stability in an injection medium.

  Cancer ablation treatment is a method of treating cancer by cauterizing cancer cells, taking advantage of the fact that cancer cells are more susceptible to heat damage than normal cells. In recent years, cancer iron tumors have been introduced by introducing ferromagnetic iron oxide particles into the body. Research on a method for cauterizing cancer by applying an AC magnetic field from the outside and generating heat due to magnetic hysteresis loss is underway (for example, Patent Document 1). As a method of ablating cancer using magnetic particles, a method of generating heat by applying an alternating magnetic field to superparamagnetic iron oxide particles from the outside has been studied, but this method uses fluctuation of magnetic moment as a magnetic field. In order to absorb magnetic field energy by resonating, a very high frequency is required, and since heat generation efficiency is essentially low, it has not been put into practical use. On the other hand, the method using ferromagnetic iron oxide particles is expected to be put to practical use because it is excellent in that it can generate heat efficiently at a relatively low frequency. However, at present, satisfactory heat generation efficiency is not always achieved, and accordingly, research for improving heat generation efficiency is being conducted energetically. As a method for improving the heat generation efficiency of the ferromagnetic iron oxide particles, for example, in order to increase the magnetic hysteresis loss, the coercive force, saturation magnetization, squareness ratio (ratio of residual magnetization to saturation magnetization) of the magnetic hysteresis curve A method of increasing the coercive force is conceivable, but a method of increasing the coercive force is not practical because a high applied magnetic field corresponding to the large coercive force is required, and the apparatus is large and expensive. On the other hand, the method of increasing the saturation magnetization and the squareness ratio is a practical method because it does not require a large and expensive device. However, since the ferromagnetic iron oxide particles proposed so far have a spherical or elliptical shape, it is necessary to add a different element such as cobalt in order to increase the saturation magnetization and the squareness ratio of the magnetic hysteresis curve. was there. For this reason, since the coercive force increases as the saturation magnetization and squareness ratio increase, the saturation magnetization and squareness ratio of the ferromagnetic iron oxide particles having a spherical or elliptical shape are set so as not to increase too much. Increasing the size is essentially difficult, and there is a limit to improving the heat generation efficiency.

  In view of the above points, the present inventors have developed a cancer ablation having excellent heat generation characteristics by increasing the magnetic hysteresis loss by increasing the saturation magnetization and squareness ratio of the magnetic hysteresis curve without adding different elements. Aiming at providing ferromagnetic iron oxide particles for treatment, ferromagnetic iron oxide particles having a plate-like shape manufactured via goethite (α-FeOOH) using a trivalent iron compound as a starting material Reported in Non-Patent Document 1 that it is an excellent one that satisfies the above requirements.

JP 2010-89991 A

M.M. Kishimoto et al., Journal of Magnetics and Magnetic Materials, 324 (2012) 1285-1289.

The ferromagnetic iron oxide particles having a plate-like shape reported by the present inventors in Non-Patent Document 1 incorporate a step of coating the surface of goethite particles with a SiO ₂ coating during production. The ferromagnetic iron oxide particles are ferromagnetic iron oxides obtained by heat-dehydrating goethite in air to convert it into hematite (α-Fe ₂ O ₃ ) and then heating and reducing hematite in hydrogen gas. Since it is manufactured by converting to magnetite (Fe ₃ O ₄ ), in order to prevent the particles from being sintered and deformed by a heat treatment performed dry in these conversion steps, the plate-like shape is deformed. (In particular, the step of converting hematite into magnetite is usually performed at a high temperature of 300 ° C. or higher, and therefore, there is a strong possibility that the particles will be deformed unless the surface is previously coated with a SiO ₂ coating). However, covering the particles with a SiO ₂ coating may cause problems such as a decrease in magnetic properties (for example, saturation magnetization) of the ferromagnetic iron oxide, and particles for improving dispersibility in the injection medium. In the case of surface modification, there is a problem that it may become an obstruction factor. Further, as described above, the ferromagnetic iron oxide particles having a plate shape reported by the present inventors in Non-Patent Document 1 are produced by dry heat treatment as described above. Due to the strong interaction such as cohesive force and hydrogen bonding between particles, there is room for improvement in dispersibility in the injection medium. As a method for solving this problem, there is a method of modifying the surface of the particle. As described above, the SiO ₂ coating existing on the surface of the particle may be an inhibiting factor.
Accordingly, an object of the present invention is to provide a method for producing ferromagnetic iron oxide particles and the like suitable for cancer ablation treatment that have excellent heat generation characteristics and excellent dispersion stability with respect to an injection medium.

  As a result of intensive studies in view of the above points, the present inventors dispersed heat-treated iron hydroxide particles and hematite particles such as goethite particles having a plate-like shape in a polyhydric alcohol, It has been found that it can be converted into magnetite particles having excellent exothermic properties without causing deformation of the plate-like shape of the particles, and the magnetite particles thus obtained are excellent in dispersion stability with respect to an injection medium.

The manufacturing method of the ferromagnetic iron oxide particles of the present invention based on the above knowledge is, as described in claim 1, to disperse iron hydroxide particles and / or hematite particles in a polyhydric alcohol and heat-treat. Features.
The manufacturing method according to claim 2 is characterized in that, in the manufacturing method according to claim 1, the iron hydroxide particles and / or the hematite particles have a plate-like shape.
The manufacturing method according to claim 3 is the manufacturing method according to claim 1 or 2, wherein the iron hydroxide particles are goethite particles.
The production method according to claim 4 is the production method according to any one of claims 1 to 3, wherein the polyhydric alcohol is selected from ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, and glycerin. It is characterized by being at least one kind.
The manufacturing method according to claim 5 is the manufacturing method according to any one of claims 1 to 4, wherein the polyhydric alcohol is a hydrous polyhydric alcohol.
The manufacturing method according to claim 6 is the manufacturing method according to any one of claims 1 to 5, wherein the heating temperature is 200 to 350 ° C.
Moreover, the ferromagnetic iron oxide particles for cancer ablation treatment of the present invention have a plate-like shape having a major axis of 20 to 200 nm and a major axis to thickness ratio of 1.5 to 30, as described in claim 7. The magnetic properties are such that the coercive force is 30 to 400 Oe, the saturation magnetization is 30 to 100 emu / g, and the squareness ratio of the magnetic hysteresis curve is 0.20 to 0.50 (however, SiO ₂ is formed on the surface of the particles) No coating).
Further, the ferromagnetic iron oxide particles for cancer ablation treatment according to claim 8 is the ferromagnetic iron oxide particles for cancer ablation treatment according to claim 7, wherein the iron oxide is an intermediate between magnetite, gamma iron oxide, magnetite and gamma iron oxide. It is one of the iron oxides in a state.
Further, the ferromagnetic iron oxide particles for cancer ablation treatment according to claim 9 is the ferromagnetic iron oxide particles for cancer ablation treatment according to claim 7 or 8, wherein the particle surface is modified with a surface modifier. Features.
Moreover, the ferromagnetic iron oxide particle dispersion composition for cancer ablation treatment of the present invention has a plate-like shape having a major axis of 20 to 200 nm and a major axis to thickness ratio of 1.5 to 30 as described in claim 10. Ferromagnetic iron oxide particles for cancer ablation treatment having magnetic properties of having a coercive force of 30 to 400 Oe, a saturation magnetization of 30 to 100 emu / g, and a squareness ratio of a magnetic hysteresis curve of 0.20 to 0.50 ( However, it is characterized in that the particle surface has no SiO ₂ coating) dispersed in an injection medium.

  ADVANTAGE OF THE INVENTION According to this invention, it can provide the manufacturing method of the ferromagnetic iron oxide particle etc. which are suitable for the cancer ablation treatment which has the outstanding heat_generation | fever characteristic and is excellent in the dispersion stability with respect to an injection medium.

2 is a TEM photograph of goethite particles obtained in Example 1. 2 is a TEM photograph of hematite particles. It is the same TEM photograph of magnetite particles. 4 is a TEM photograph of goethite particles obtained in Example 3. It is the same TEM photograph of magnetite particles. 4 is a TEM photograph of magnetite particles obtained in Example 4.

  The method for producing ferromagnetic iron oxide particles of the present invention is characterized in that iron hydroxide particles and / or hematite particles are dispersed in a polyhydric alcohol and heat-treated.

  The iron hydroxide particles used as a raw material in the method for producing ferromagnetic iron oxide particles of the present invention may be a single substance or a mixture of plural substances. Specific examples thereof include particles made of goethite (α-FeOOH), akagenite (β-FeOOH), lepidoccrosite (γ-FeOOH), iron hydroxide (II), iron hydroxide (III), and the like. These particles are a precipitate obtained by mixing an aqueous solution of a divalent iron compound such as ferrous chloride, ferrous sulfate or ferrous nitrate with an alkali such as sodium hydroxide, potassium hydroxide or ammonia ( It may be a particle having a needle-like shape obtained by oxidizing and crystallizing (including iron hydroxide), but a ferromagnetic iron oxide particle having a plate-like shape suitable for cancer ablation treatment, for example, When producing ferromagnetic iron oxide particles having a plate shape having a major axis of 20 to 200 nm and a ratio of major axis to thickness of 1.5 to 30, particles having the same plate shape are desirable. For example, in the case of goethite particles, such plate-like particles are produced by subjecting a precipitate obtained by mixing an alkali and an amine compound to an aqueous solution of a trivalent iron compound to a hydrothermal reaction. be able to. In this production method, a precipitate (including iron hydroxide) obtained by mixing an alkali and an amine compound in an aqueous solution of a trivalent iron compound such as ferric chloride, ferric sulfate, or ferric nitrate. Based on the knowledge found by the present inventors that goethite particles having a plate-like shape can be obtained when subjected to a hydrothermal reaction. Examples of the alkali include sodium hydroxide, potassium hydroxide, and ammonia, and sodium hydroxide can be preferably used. Examples of the amine compound (which means a compound having an amino group in the molecule) include alcohol amines having 2 to 10 carbon atoms such as ethanolamine and N-methylethanolamine. In order to convert all the trivalent iron compounds into iron hydroxides, alkali is required at least three times the amount of iron (molar ratio). Therefore, the mixing ratio of the trivalent iron compound and the alkali is preferably, for example, 1: 3 to 1:15 (molar ratio). The mixing ratio of alkali and amine compound is preferably 1: 1 to 1: 5 (weight ratio). The mixing of the alkali and amine compound into the aqueous solution of the trivalent iron compound may be performed by, for example, mixing the aqueous solution of the trivalent iron compound with stirring into the aqueous solution in which the alkali and amine compound are dissolved. The temperature of both aqueous solutions during mixing affects the size of the goethite particles, and consequently the size of the ferromagnetic iron oxide particles. For example, when the temperature of both aqueous solutions is −10 to 30 ° C., goethite particles having a plate-like shape having a major axis of 20 to 200 nm and a major axis to thickness ratio of 1.5 to 30, and eventually ferromagnetic iron oxide particles are obtained. be able to. The ratio of the major axis to the minor axis is, for example, 1 to 10, and particles having a smaller major axis are obtained as the temperature is lower. The hydrothermal reaction of a precipitate obtained by mixing an alkali and an amine compound in an aqueous solution of a trivalent iron compound is carried out, for example, at 110 to 220 ° C. for 1 to 5 hours by charging the precipitate into a pressure-resistant vessel such as an autoclave. Good. If the temperature of the hydrothermal reaction is too low, the particles are difficult to grow into a plate shape, while if too high, the particles grow too much and it is difficult to obtain particles of a predetermined size. In addition, the precipitate obtained by mixing an alkali and an amine compound in the aqueous solution of a trivalent iron compound is obtained in a room temperature environment (for example, 10 to 30 ° C.) after obtaining the precipitate. By performing the hydrothermal reaction after aging for about half a day to 2 days, goethite particles having a plate-like shape of a predetermined size can be easily obtained.

  When hematite particles are used as a raw material in the method for producing ferromagnetic iron oxide particles of the present invention, hematite particles can be obtained by heating and dehydrating iron hydroxide particles. Heat dehydration of the iron hydroxide particles can be performed by a method known per se, for example, by heating the iron hydroxide particles in air for 5 minutes to 5 hours. In order to obtain hematite particles having the shape of iron hydroxide particles having a plate shape, the heating temperature is preferably 200 to 300 ° C. If the heating temperature is too low, dehydration may not proceed sufficiently, while if it is too high, the particles may sinter and deform.

  Examples of the polyhydric alcohol for dispersing the iron hydroxide particles and hematite particles used as raw materials in the method for producing ferromagnetic iron oxide particles of the present invention include ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, and glycerin. Can be mentioned. These may be used singly or in combination of a plurality of types.

Ferromagnetic iron oxide particles can be obtained by dispersing iron hydroxide particles or hematite particles in a polyhydric alcohol and performing heat treatment. This is because hematite particles are converted to ferromagnetic iron oxide particles by the reducing power of the polyhydric alcohol. When iron hydroxide particles are used as a raw material, the iron hydroxide particles are dehydrated in the system and are removed from the hematite. After being converted into particles, it is converted into ferromagnetic iron oxide particles. The ferromagnetic iron oxide particles produced in this way are not dry-heated as in the method described in Non-Patent Document 1, but wet in a state where individual particles are dispersed in a polyhydric alcohol. Since it has been heat-treated, interaction such as magnetic cohesion between particles and hydrogen bonding between particles is not strong, so that it has excellent dispersion stability with respect to an injection medium. It is well known to those skilled in the art that polyhydric alcohols have a reducing power, and it is known that they can be used, for example, when metal ions and metal alkoxides are reduced to deposit metals. It is cubic and it is not possible to obtain particles having a plate shape. On the other hand, according to the method for producing ferromagnetic iron oxide particles using the reducing power of the polyhydric alcohol of the present invention, if the iron hydroxide particles and hematite particles used as raw materials have a plate-like shape Thus, it is possible to obtain ferromagnetic iron oxide particles that retain their shape. The obtained ferromagnetic iron oxide particles may be separated from the polyhydric alcohol by washing with water, and then dried in air, for example. The ferromagnetic iron oxide produced by the present invention is usually magnetite (Fe ₃ O ₄ ), but the magnetite is heated and oxidized in air at 200 to 300 ° C. for 1 to 30 minutes to produce gamma iron oxide (γ− Fe ₂ O ₃ ). Further, if the temperature condition of the heat oxidation is lower than, for example, 200 ° C., iron oxide in an intermediate state between magnetite and gamma iron oxide can be obtained. These ferromagnetic iron oxides are all suitable for cancer ablation treatment.

  The heat treatment of the dispersion in which iron hydroxide particles or hematite particles are dispersed in polyhydric alcohol is desirably performed at 200 ° C. or higher, and more desirably performed at 250 ° C. or higher. If the heating temperature is too low, when iron hydroxide particles are used as a raw material, dehydration does not proceed sufficiently, and it may become difficult to convert to hematite particles, or the reducing power of polyhydric alcohol may not be fully demonstrated. May not be converted to ferromagnetic iron oxide particles. The upper limit of the heating temperature is preferably 350 ° C. If the heating temperature is too high, when it is desired to obtain ferromagnetic iron oxide particles that retain the shape of iron hydroxide particles or hematite particles, it may be difficult to obtain such particles due to deformation of the particles, and there are many cases that occur in the system. The ferromagnetic iron oxide particles converted from the hematite particles are oxidized by the decomposition product of the monohydric alcohol, so that the magnetic properties (for example, saturation magnetization) may be lowered. Among the polyhydric alcohols mentioned above, triethylene glycol, tetraethylene glycol, and glycerin are particularly desirable as a medium in that they can be heated to 250 ° C. or higher at normal pressure because they have boiling points of 250 ° C. or higher. However, even when ethylene glycol, diethylene glycol, polyethylene glycol, or the like is used, the dispersed iron hydroxide particles or hematite particles can be strengthened by heat treatment in a pressure vessel such as an autoclave if necessary. It can be converted into magnetic iron oxide particles. The heating time is preferably, for example, 30 minutes to 24 hours. If the heating time is too short, iron hydroxide particles and hematite particles may not be converted to ferromagnetic iron oxide particles sufficiently, while if the heating time is too long, they are converted from hematite particles by polyhydric alcohol decomposition products generated in the system. When the ferromagnetic iron oxide particles are oxidized, the magnetic properties (for example, saturation magnetization) may be reduced.

  It is desirable to disperse the iron hydroxide particles and hematite particles in the polyhydric alcohol so that the amount of polyhydric alcohol is 5 to 500 times the amount of iron hydroxide particles and hematite particles (weight ratio). . If the amount of polyhydric alcohol is too small relative to the amount of iron hydroxide particles or hematite particles, there is a risk that the reducing power of polyhydric alcohol to hematite particles is not sufficient, which makes it difficult for hematite particles to be converted to ferromagnetic iron oxide particles. On the other hand, if it is more than necessary, it will only increase costs.

  The polyhydric alcohol in which iron hydroxide particles and hematite particles are dispersed may contain water. When hydrous polyhydric alcohol is used as a medium, the hematite particles undergo a hydrothermal reaction with water as well as a reduction reaction with polyhydric alcohol, and are converted to ferromagnetic iron oxide particles by being easily reduced during particle dissolution and precipitation. It becomes easy to be done. However, the water-containing polyhydric alcohol desirably has a water amount of 10 times or less (weight ratio) with respect to the amount of the polyhydric alcohol. If the amount of water is too much with respect to the amount of polyhydric alcohol, coarsening and deformation due to dissolution and precipitation of particles may become remarkable. The embodiment using the water-containing polyhydric alcohol as the medium can be performed by adding water to the polyhydric alcohol, and when the dispersion target is iron hydroxide particles, after washing with water when preparing the iron hydroxide particles It is also possible to disperse iron hydroxide particles containing water in polyhydric alcohol or dissolve polyhydric alcohol in a suspension of iron hydroxide particles suspended in water. Such an embodiment is advantageous in that the drying step after the preparation of the iron hydroxide particles can be omitted, and the wet processing can be consistently performed until the ferromagnetic iron oxide particles are obtained.

According to the present invention, it is possible to produce ferromagnetic iron oxide particles that retain their shape without covering the surface of iron hydroxide particles or hematite particles used as raw materials with a SiO ₂ coating. Therefore, for example, by using iron hydroxide particles having a plate-like shape having a major axis of 20 to 200 nm and a ratio of the major axis to the thickness of 1.5 to 30, the same plate-like shape is obtained. Ferromagnetic iron oxide particles suitable for cancer ablation treatment having magnetic properties of coercive force of 30 to 400 Oe, saturation magnetization of 30 to 100 emu / g, and squareness ratio of magnetic hysteresis curve of 0.20 to 0.50 Can be manufactured. The coercive force of the ferromagnetic iron oxide grains having the plate shape is based on the shape magnetic anisotropy. Therefore, ferromagnetic iron oxide particles having a spherical shape or an elliptical shape that have been proposed so far, and ferromagnetic materials that have increased coercivity based on magnetocrystalline anisotropy by adding different elements such as cobalt. Since the saturation magnetization and the squareness ratio of the magnetic hysteresis curve are large compared to iron oxide particles, the magnetic hysteresis loss is large, and thus excellent heat generation efficiency is exhibited. In addition, the particle shape of the particles increases the contact area with the cancer tumor when introduced into the body and accumulated in the cancer tumor compared to particles having a spherical or elliptical shape. , Shochu efficiency is excellent. Therefore, combined with its excellent fever efficiency, a further therapeutic effect can be expected in cancer ablation treatment. Ferromagnetic iron oxide particles for cancer ablation treatment are dispersed at a concentration of, for example, 0.01 to 10 wt% in an injection medium such as water, physiological saline, or phosphate buffered saline to accumulate on target cancer cells. Thus, it is provided as a ferromagnetic iron oxide particle dispersion composition for cancer ablation treatment, which is further diluted with an injectable medium as needed and intravenously administered to humans and other mammals. Application of an external AC magnetic field to particles accumulated in cancer cells may be performed, for example, for 1 to 60 minutes per time under conditions of a frequency of 10 to 200 kHz and a maximum applied magnetic field of 100 to 1000 Oe. In addition, when dispersing the ferromagnetic iron oxide particles in the injection medium, additives such as isotonic agents and stabilizers known per se may be added as necessary. Further, when dispersing the ferromagnetic iron oxide particles in the injection medium, a polyhydric alcohol such as polyethylene glycol is added at a ratio of, for example, 10 to 1000% by weight with respect to the particles, thereby dispersing the particles in the injection medium. The sex can be increased.

  In order to complement or enhance the magnetic properties of the ferromagnetic iron oxide particles produced according to the present invention, different elements (cobalt, platinum, magnesium, zinc, nickel, titanium, etc.) are added to the ferromagnetic iron oxide particles. Also good. For example, it is possible to sharpen the rise of the magnetic hysteresis curve by adding 0.5 to 5 atomic% magnesium with respect to iron. The heat generation efficiency can be further increased by increasing the area. In addition, it is desirable that the addition amount of the different element is 0.1 to 5.0 atomic% with respect to iron. If the addition amount is too small, it is difficult to obtain the intended effect. On the other hand, if the addition amount is too large, the particles are difficult to grow into a plate shape when obtaining iron hydroxide particles.

Further, as described above, the ferromagnetic iron oxide particles produced by the present invention are excellent in dispersibility in an injection medium, but in order to further improve the dispersibility in an injection medium, the surface of the particles is modified with a surface modifier. Also good. Since the ferromagnetic iron oxide particles produced according to the present invention do not have a SiO ₂ coating on the surface, the surface modification of the particles can be performed effectively. Although the kind of surface modifier is not specifically limited, The block copolymer of the polystyrene which has a phosphite group in a polyethyleneglycol and a side chain suitably is mentioned suitably. This block copolymer is structurally roughly divided into a polyethylene glycol part and a polystyrene part having a phosphite group in the side chain, but strong Fe-O is formed by at least one phosphite group present in the polystyrene part. It can couple | bond with the surface of a ferromagnetic iron oxide particle through -P coupling | bonding. In this way, the polyethylene glycol portion of the block copolymer bonded to the surface of the particle forms a steric hindrance sufficient to sufficiently prevent the magnetic cohesive force acting between the particles on the surface of the particle. In addition, since this block copolymer has no charge in the molecule, the adhesion of ions to the surface of the particles is suppressed, so that the cohesive force due to the charge can also be prevented, resulting in excellent affinity with the injection medium. Can have. In addition, this block copolymer prevents the ferromagnetic iron oxide particles from coming into direct contact with various biological components or adsorbing biological components on the surface of the particles in the living body. Moreover, the magnetic properties and heat generation properties of the ferromagnetic iron oxide particles are not impaired by bonding the block copolymer to the surface.

  As a specific example of a block copolymer of polyethylene glycol and a polystyrene having a phosphite group in the side chain, polyethylene glycol-b-poly (4-vinylbenzylphosphonate) represented by the following general formula (I) (hereinafter referred to as “polyethylene glycol-b-poly (4-vinylbenzylphosphonate)”) Abbreviated as “PEG-b-PVBP”).

(In the formula, R is an alkyl group which may have a substituent, L is — (CH ₂ ) ₁ S—, —CO (CH ₂ ) ₁ S—, —COO (CH ₂ ) ₁ S—, — COC _{(CH 3) l} - linking group, selected from the group consisting of l is an integer of from 1 to 5, m is an integer of 5 to 500, n is an integer of 2 to 30)

Here, the alkyl group in the alkyl group which may have a substituent is, for example, a linear or branched alkyl group having 1 to 12 carbon atoms, and specifically includes a methyl group, an ethyl group, Examples include propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, hexyl group, isohexyl group, heptyl group, dodecyl group and the like. Examples of the substituent that the alkyl group may have include a lower alkoxy group and an R ¹ R ² CH— group. The lower alkoxy group is, for example, a linear or branched alkoxy group having 1 to 4 carbon atoms, and specific examples thereof include methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group, sec -Butoxy group, tert-butoxy group and the like can be mentioned. ^{R 1} and ^{R 2} in R ¹ R ² CH- group can be each independently a lower alkoxy group (as mentioned above is what it means), ^{R 1} and ^{R 2} together -O ( _{CH 2) 2 O -, -} O (CH 2) 3 O- or -O _{(CH 2)} 4 is O-.

  PEG-b-PVBP represented by the above general formula (I) is, for example, a known surface modifier for superparamagnetic iron oxide particles. Ujie et al., Colloids and Surfaces B: Biointerfaces, 88, 771-778 (2011) describes that superparamagnetic iron oxide particles surface-modified with PEG-b-PVBP can be used as MRI sensitizers. Yes. However, there is no report on the surface modification of ferromagnetic iron oxide particles using PEG-b-PVBP.

  PEG-b-PVBP is obtained by subjecting polyethylene glycol to block polymerization of polychloromethylstyrene to obtain polyethylene glycol-b-polychloromethylstyrene according to the method described in Ujiie et al. It can be prepared by converting to a group. The number average molecular weight of PEG-b-PVBP is desirably 1000 to 30000. If the number average molecular weight is less than 1000, there may be a problem that the number of phosphonate groups in the molecule is small, so that the surface cannot be firmly and abundantly bonded to the surface of the ferromagnetic iron oxide particles. This may cause a problem that the steric hindrance formed on the surface of the particles becomes too large and the number of molecular bonds decreases.

  As a method of binding PEG-b-PVBP to the surface of the ferromagnetic iron oxide particles, PEG-b-PVBP is dissolved in a dispersion liquid in which the particles are dispersed in water and / or a hydrophilic solvent as a dispersion medium. The method of performing is mentioned. In Ujiie et al., Which describes superparamagnetic iron oxide particles having PEG-b-PVBP bonded to the surface, PEG-b-PVBP is dissolved in an aqueous solution of ferrous chloride and ferric chloride, and then ammonia. Is added at the same time to form particles and bond PEG-b-PVBP to the surface of the particles. This method is directly applied to the surface of the ferromagnetic iron oxide particles having a plate-like shape as PEG-b-PVBP. It is difficult to adopt as a method of combining the two. As described above, since it is necessary to perform a hydrothermal reaction or heat treatment at 100 ° C. or higher in order to obtain these particles, unless any heat-resistant treatment is applied to PEG-b-PVBP in advance, This is because PEG-b-PVBP may be denatured or decomposed by being exposed to a high temperature at a stage.

  Examples of the hydrophilic solvent that can be used for dispersing the ferromagnetic iron oxide particles include alcohols such as methanol and ethanol, acetone, and acetonitrile. The amount of PEG-b-PVBP dissolved in a dispersion in which particles are dispersed in water and / or a hydrophilic solvent is preferably about 0.1 to 10 times the weight of the particles (weight ratio). If the dissolved amount of PEG-b-PVBP is too small, PEG-b-PVBP may not be abundantly bound to the surface of the particles. On the other hand, if the dissolved amount is too large, the amount of PEG-b-PVBP in the dispersion liquid Therefore, there is a possibility that the binding between the particles and PEG-b-PVBP may hardly proceed. The binding of PEG-b-PVBP to the surface of the particles is desirably performed in a temperature range of 30 to 60 ° C. If the temperature is too low, the bonding between the particles and PEG-b-PVBP may not proceed smoothly, whereas if the temperature is too high, PEG-b-PVBP may be denatured or decomposed.

  After binding PEG-b-PVBP to the surface of the ferromagnetic iron oxide particles, if there is a precipitate, the precipitate is removed, and if the dispersion medium is further removed, excellent heat generation of the ferromagnetic iron oxide particles It is possible to obtain powdery surface-modified ferromagnetic iron oxide particles having excellent dispersion stability with respect to an injection medium while maintaining the properties.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in detail, this invention is limited to the following description and is not interpreted.

Example 1: Production of ferromagnetic iron oxide particles (Part 1)
(A) Preparation of goethite particles having a plate shape 30 g of ferric chloride was dissolved in 150 g of water. In addition, 45 g of sodium hydroxide and 90 g of ethanolamine were dissolved in 1100 g of water. The aqueous solution of ferric chloride was cooled to −1.8 ° C. in a freezer, and the aqueous solution of sodium hydroxide and ethanolamine was cooled to −6.4 ° C. in a freezer. Since each aqueous solution has a large amount of ions dissolved therein and has a low freezing point, it was cooled to a temperature at 0 ° C. or lower so as not to freeze. Next, while stirring the latter aqueous solution in a room temperature environment, the former aqueous solution was dropped therein, and then stirring was continued for 30 minutes to obtain a precipitate containing iron hydroxide. The temperature of the suspension immediately after dropping and mixing was −2.5 ° C., and the temperature of the suspension after mixing for 30 minutes was 2.0 ° C. As described above, the size of the finally obtained ferromagnetic iron oxide particles having a plate-like shape is substantially determined by the temperature at the time of mixing both aqueous solutions, and the particle size decreases as the temperature decreases. Next, the precipitate was left to mature for one day in a room temperature environment, then the precipitate was collected, charged in an autoclave and subjected to a hydrothermal reaction at 130 ° C. for 2 hours, washed with water and washed with sodium. The goethite particles were obtained by removing ions and ethanolamine and then drying in air (confirmation of goethite by structural analysis by X-ray diffraction). A transmission electron microscope (TEM) photograph of the obtained goethite particles is shown in FIG. The goethite particles obtained by this method had an average major axis of about 30 nm and an average minor axis of about 15 nm, and the ratio of the major axis to the minor axis was about 2. In addition, observation by a scanning electron microscope (SEM) confirmed that the particles had a plate-like shape with a thickness of about 5 nm (ratio of major axis to thickness was about 6).

(B) Conversion of goethite particles having a plate-like shape to hematite particles The goethite particles obtained in (A) were heated and dehydrated in air at 250 ° C. for 10 minutes to obtain hematite particles (being hematite (Confirmed by structural analysis by X-ray diffraction). A TEM photograph of the obtained hematite particles is shown in FIG. The hematite particles obtained by this method retain the plate-like shape that the goethite particles had, but a large number of pores (size is approximately 10 nm or less) formed by dehydration reaction of the goethite particles on the surface of the particles. ) And irregularities.

(C) Conversion of hematite particles having a plate-like shape into magnetite particles by wet reduction in polyhydric alcohol 100 g of tetraethylene glycol is added to 500 mg of the hematite particles obtained in (B) and subjected to ultrasonic dispersion treatment for 2 hours. To obtain a uniform dispersion. The obtained dispersion was put in a stainless steel container and covered with a lid, and then heat-treated in an oven at 290 ° C. for 2 hours. Two hours later, after naturally cooling in an oven and returning to room temperature, the container is taken out. After the dispersion in the container is washed with water to remove tetraethylene glycol, the magnetite particles are dried in air. Obtained (confirmed to be magnetite by structural analysis by X-ray diffraction). A TEM photograph of the obtained magnetite particles is shown in FIG. The magnetite particles obtained by this method retain the plate-like shape that the goethite particles had, but had a large number of pores (size is approximately 10 nm or less) and irregularities on the surface of the particles. The obtained magnetite particles had a coercive force of 155 Oe, a saturation magnetization of 72.1 emu / g, and a squareness ratio of a magnetic hysteresis curve of 0.42 (maximum applied magnetic field using a sample vibration type magnetometer manufactured by DMS). Measured at 13000 Oe). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), they had excellent exothermic characteristics. In addition, 500 mg of magnetite particles suspended in water before being dried in air are put into a beaker, 200 g of water is added and ultrasonic dispersion treatment is performed for 2 hours to obtain a uniform dispersion, and then left to stand. When the time until the magnetite particles in the water began to settle at the bottom of the beaker was measured, it was about 60 minutes, and it was found that the magnetite particles had excellent dispersion stability with respect to water.

Example 2: Production of ferromagnetic iron oxide particles (Part 2)
Magnetite particles were obtained by wet reduction of the goethite particles obtained in (A) of Example 1 in the same manner as in the method described in (C) of Example 1 (magnetite is a structure by X-ray diffraction) Confirmed by analysis). The magnetite particles obtained by this method retain the plate-like shape that the goethite particles obtained in Example 1 (A) had, but many pores (size is approximately 10 nm on the surface of the particles). Or the like). The obtained magnetite particles had a coercive force of 160 Oe, a saturation magnetization of 74.8 emu / g, and a squareness ratio of a magnetic hysteresis curve of 0.40 (maximum applied magnetic field using a sample vibration type magnetometer manufactured by DMS). Measured at 13000 Oe). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), they had excellent exothermic characteristics. Further, when the dispersion stability of the magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the time until the magnetite particles in the water began to settle at the bottom of the beaker was about 50 minutes. As with the magnetite particles obtained in Example 1 (C), it was found to have excellent dispersion stability with respect to water.

Example 3: Production of ferromagnetic iron oxide particles (Part 3)
(A) Preparation of goethite particles having a plate shape 30 g of ferric chloride was dissolved in 150 g of water. In addition, 45 g of sodium hydroxide and 90 g of ethanolamine were dissolved in 1100 g of water. The aqueous solution of ferric chloride was cooled to -1.2 ° C in a freezer, and the aqueous solution of sodium hydroxide and ethanolamine was cooled to -3.8 ° C in a freezer. Next, while stirring the latter aqueous solution in a room temperature environment, the former aqueous solution was dropped therein, and then stirring was continued for 30 minutes to obtain a precipitate containing iron hydroxide. The temperature of the suspension immediately after dropping and mixing was −0.8 ° C., and the temperature of the suspension after mixing for 30 minutes was 3.0 ° C. Next, the precipitate was left to mature for one day in a room temperature environment, then the precipitate was collected, charged in an autoclave and subjected to a hydrothermal reaction at 130 ° C. for 2 hours, washed with water and washed with sodium. The goethite particles were obtained by removing ions and ethanolamine and then drying in air (confirmation of goethite by structural analysis by X-ray diffraction). A TEM photograph of the obtained goethite particles is shown in FIG. The goethite particles obtained by this method had an average major axis of about 50 nm and an average minor axis of about 20 nm, and the ratio of the major axis to the minor axis was about 2.5. Moreover, it was confirmed by SEM observation that the particles had a plate-like shape with a thickness of about 5 nm (ratio of major axis to thickness was about 10).

(B) Conversion of goethite particles having a plate-like shape to hematite particles The goethite particles obtained in (A) are heated and dehydrated in the same manner as in the method described in (B) of Example 1 to obtain hematite particles. (It was confirmed that it was hematite by structural analysis by X-ray diffraction). The hematite particles obtained by this method retain the plate-like shape that the goethite particles had, but a large number of pores (size is approximately 10 nm or less) formed by dehydration reaction of the goethite particles on the surface of the particles. ) And irregularities.

(C) Conversion of hematite particles having a plate-like shape by wet reduction in polyhydric alcohol into magnetite particles The hematite particles obtained in (B) were treated in the same manner as in the method described in (C) of Example 1. Magnetite particles were obtained by wet reduction (confirmed to be magnetite by structural analysis by X-ray diffraction). A TEM photograph of the obtained magnetite particles is shown in FIG. The magnetite particles obtained by this method retain the plate-like shape that the goethite particles had, but had a large number of pores (size is approximately 10 nm or less) and irregularities on the surface of the particles. The obtained magnetite particles had a coercive force of 175 Oe, a saturation magnetization of 80.2 emu / g, and a squareness ratio of a magnetic hysteresis curve of 0.44 (maximum applied magnetic field using a sample vibration type magnetometer manufactured by DMS). Measured at 13000 Oe). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), they had excellent exothermic characteristics. Moreover, when the dispersion stability of the magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the time until the magnetite particles in the water began to settle at the bottom of the beaker was about 30 minutes. As with the magnetite particles obtained in Example 1 (C), it was found to have excellent dispersion stability with respect to water.

Example 4: Production of ferromagnetic iron oxide particles (Part 4)
A mixture of 500 mg of goethite particles obtained in (A) of Example 3 and 500 mg of water (the goethite particles in a suspended state in water before being dried in air were dried without being completely dried, and the amount of goethite contained 100 g of tetraethylene glycol was added to the one prepared after knowing the amount of water), and ultrasonic dispersion treatment was performed for 2 hours to obtain a uniform dispersion. The obtained dispersion was charged into an autoclave and heated under pressure at 290 ° C. for 2 hours (the autoclave was used to prevent water evaporation). Two hours later, the dispersion in the autoclave was washed with water to remove tetraethylene glycol, and then dried in air to obtain magnetite particles (confirmed to be magnetite by structural analysis by X-ray diffraction) ). A TEM photograph of the obtained magnetite particles is shown in FIG. The magnetite particles obtained by this method had a shape slightly coarser than the plate-like shape that the goethite particles obtained in Example 3 (A) had, but the basic shape was retained. It had a large number of pores (size is approximately 10 nm or less) and irregularities on the surface of the particles. The obtained magnetite particles had a coercive force of 193 Oe, a saturation magnetization of 83.5 emu / g, and a squareness ratio of a magnetic hysteresis curve of 0.35 (maximum applied magnetic field using a sample vibration type magnetometer manufactured by DMS). Measured at 13000 Oe). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), they had excellent exothermic characteristics. Further, when the dispersion stability of the magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the time until the magnetite particles in the water began to settle at the bottom of the beaker was about 20 minutes. As with the magnetite particles obtained in Example 1 (C), it was found to have excellent dispersion stability with respect to water.

Example 5: Production of ferromagnetic iron oxide particles (part 5)
500 mg of water and 100 g of tetraethylene glycol were added to 500 mg of the hematite particles obtained in (B) of Example 1, and ultrasonic dispersion treatment was performed for 2 hours to obtain a uniform dispersion. The obtained dispersion was charged in an autoclave and heat-treated at 290 ° C. for 2 hours under pressure. Two hours later, the dispersion in the autoclave was washed with water to remove tetraethylene glycol, and then dried in air to obtain magnetite particles (confirmed to be magnetite by structural analysis by X-ray diffraction) ). The magnetite particles obtained by this method had a shape slightly coarser than the plate-like shape that the goethite particles obtained in Example 1 (A) had, but the basic shape was retained. It had a large number of pores (size is approximately 10 nm or less) and irregularities on the surface of the particles. The obtained magnetite particles had a coercive force of 161 Oe, a saturation magnetization of 75.1 emu / g, and a squareness ratio of a magnetic hysteresis curve of 0.38 (maximum applied magnetic field using a sample vibration type magnetometer manufactured by DMS). Measured at 13000 Oe). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), they had excellent exothermic characteristics. Moreover, when the dispersion stability of the magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the time until the magnetite particles in the water began to settle at the bottom of the beaker was about 30 minutes. As with the magnetite particles obtained in Example 1 (C), it was found to have excellent dispersion stability with respect to water.

Example 6: Production of ferromagnetic iron oxide particles (Part 6)
Magnetite particles were obtained by performing wet reduction in the same manner as described in Example 1 (C) except that triethylene glycol was used as the polyhydric alcohol and the heating temperature was set to 270 ° C. (Confirmed by structural analysis by X-ray diffraction).

Example 7: Production of ferromagnetic iron oxide particles (Part 7)
Magnetite particles were obtained by wet reduction in the same manner as in Example 5 except that diethylene glycol was used as the polyhydric alcohol (confirmed that it was magnetite by structural analysis by X-ray diffraction).

Example 8: Production of ferromagnetic iron oxide particles (Part 8)
Magnetite particles were obtained by wet reduction in the same manner as in Example 5 except that ethylene glycol was used as the polyhydric alcohol (confirmation of magnetite by structural analysis by X-ray diffraction).

Example 9: Production of ferromagnetic iron oxide particles (No. 9)
100 g of polyethylene glycol (molecular weight: 200 to 600) was added to 500 mg of the goethite particles obtained in (A) of Example 1, and ultrasonic dispersion treatment was performed for 2 hours to obtain a uniform dispersion. The obtained dispersion was charged in an autoclave and heat-treated at 290 ° C. for 2 hours under pressure. After 2 hours, the dispersion in the autoclave was washed with water to remove polyethylene glycol, and then dried in air to obtain magnetite particles (confirmed to be magnetite by structural analysis by X-ray diffraction) .

Example 10: Production of ferromagnetic iron oxide particles (No. 10)
Magnetite particles were obtained by wet reduction in the same manner as described in Example 1 (C) except that glycerin was used as the polyhydric alcohol and the heating temperature was 280 ° C. (Confirmed by structural analysis by X-ray diffraction).

Example 11: Production of surface-modified ferromagnetic iron oxide particles Obtained in Example 1 using polyethylene glycol as a surface modifier and PEG-b-PVBP, which is a block copolymer of polystyrene having a phosphite group in the side chain. The surface of the magnetite particles was modified. PEG-b-PVBP was synthesized according to the method described in Ujiie et al. (See synthesis scheme below). The magnetite particles 0.8 mg obtained in Example 1 were charged into a 100 cc screw tube, and 80 g of ethanol was further added, followed by ultrasonic dispersion for about 4 hours. When the obtained dispersion was allowed to stand for 1 week, some particles precipitated on the bottom of the screw tube. The supernatant in the screw tube was collected to obtain a dispersion of magnetite particles. Next, 2.0 g of this dispersion was charged into a 10 cc screw tube, and then PEG-b-PVBP was added to the magnetite particles at a weight ratio of 50% and dissolved while ultrasonically dispersing. The obtained dispersion of magnetite particles in which PEG-b-PVBP is dissolved is placed in a screw tube and left to stand at 50 ° C. for 2 days in a covered state to bind PEG-b-PVBP to the surface of the magnetite particles. I let you. The lid of the screw tube was removed and placed in a dryer at 30 ° C., and ethanol was dried and removed while stirring the dispersion, thereby obtaining magnetite particles having PEG-b-PVBP bonded to the powdery surface. The magnetic properties and heat generation properties of the surface-modified magnetite particles were not substantially different from those of the magnetite particles before surface modification. Further, when the dispersion stability of the surface-modified magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the surface-modified magnetite particles in water settled on the bottom of the beaker after 24 hours. No oozing phenomenon was observed, and it was found that the surface-modified magnetite particles have extremely excellent dispersion stability with respect to water.

Comparative Example 1: Production of ferromagnetic iron oxide particles having a SiO ₂ coating on the surface The goethite particles (before drying in air) obtained in (A) of Example 1 were suspended in water. Then, sodium silicate was dissolved with respect to goethite particles so as to be 10% by weight in terms of SiO ₂ . The suspension after dissolving sodium silicate had a pH of about 10 because sodium silicate was strongly alkaline. The suspension in which sodium silicate is dissolved is diluted with dilute hydrochloric acid while stirring to neutralize the pH to be in the range of 7-8, and the stirring is continued for 3 hours, so that the goethite particles are coated with the SiO ₂ coating on the surface. Covered. Next, the goethite particles surface-coated with the SiO ₂ coating were washed with water and dried, and then the goethite particles were converted to hematite particles by heating and dehydrating in air at 500 ° C. for 1 hour. The particles were heated and reduced in hydrogen gas at 380 ° C. for 1 hour to convert the hematite particles into magnetite particles (confirmation of magnetite by structural analysis by X-ray diffraction). The magnetite particles obtained by this method had a shape slightly contracted from the plate-like shape that the goethite particles obtained in Example 1 (A) had, but the basic shape was retained. The surface of the particles had a large number of pores (size is approximately 10 nm or less) and irregularities. The obtained magnetite particles had a coercive force of 118 Oe, a saturation magnetization of 57.4 emu / g, and a squareness ratio of the magnetic hysteresis curve of 0.40. From the magnetic properties of the magnetite particles obtained in (C) of Example 1 (Measured with a maximum applied magnetic field of 13000 Oe using a sample vibration type magnetometer manufactured by DMS). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), it was inferior to the exothermic characteristics of the magnetite particles obtained in (C) of Example 1. It was. Further, when the dispersion stability of the magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the time until the magnetite particles in the water began to settle at the bottom of the beaker was about 10 minutes. It was found that the dispersion stability with respect to water was inferior to the magnetite particles obtained in Example 1 (C).

Comparative Example 2: Production of ferromagnetic iron oxide particles having no SiO ₂ coating on the surface by dry reduction By heating and reducing the hematite particles obtained in (B) of Example 1 at 330 ° C. for 1 hour in hydrogen gas The hematite particles were converted to magnetite particles (confirmed to be magnetite by structural analysis by X-ray diffraction). The magnetite particles obtained by this method have a spherical shape with a particle size of about 40 nm, and the particles were sintered by the heat treatment, and the plate shape was deformed. The obtained magnetite particles have a coercive force of 65 Oe, a saturation magnetization of 80.5 emu / g, and a squareness ratio of the magnetic hysteresis curve of 0.20. From the magnetic properties of the magnetite particles obtained in (C) of Example 1 (Measured with a maximum applied magnetic field of 13000 Oe using a sample vibration type magnetometer manufactured by DMS). E. As a result of examining the exothermic characteristics of the magnetite particles according to the method of Kita et al. (J. Phys. D. 43 (2010) 474011), it was inferior to the exothermic characteristics of the magnetite particles obtained in (C) of Example 1. It was. Further, when the dispersion stability of the magnetite particles in water was evaluated in the same manner as in the method described in Example 1 (C), the time until the magnetite particles in the water began to settle at the bottom of the beaker was about 10 seconds. It was found that there was almost no dispersion stability in water.

Summary:
It is known to those skilled in the art that the reducing power of polyhydric alcohol is weak compared to the reducing power of hydrogen, etc., and its use has been used so far, for example, when metal ions or metal alkoxides that are easily reduced are used as raw materials. However, in the present invention, hematite particles can be converted into magnetite particles by utilizing the reducing power of polyhydric alcohol because the particles are small (the major axis is less than 1 μm) or the particles have a plate-like shape. When it has, it is guessed that it contributes that it is easy to be reduced because the surface area of the particles is large.

Formulation Example 1:
A dispersion composition for intravenous administration was prepared by dispersing the magnetite particles produced in Example 1 in water in a concentration range of 0.05 to 5 wt%.

  The present invention has industrial applicability in that it can provide a method for producing ferromagnetic iron oxide particles and the like suitable for cancer ablation treatment having excellent exothermic characteristics and excellent dispersion stability in an injection medium. Have.

Claims (10)

  A method for producing ferromagnetic iron oxide particles, wherein iron hydroxide particles and / or hematite particles are dispersed in a polyhydric alcohol and heat-treated.   The method according to claim 1, wherein the iron hydroxide particles and / or hematite particles have a plate-like shape.   The method according to claim 1 or 2, wherein the iron hydroxide particles are goethite particles.   4. The production method according to claim 1, wherein the polyhydric alcohol is at least one selected from ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, polyethylene glycol, and glycerin.   The production method according to claim 1, wherein the polyhydric alcohol is a hydrous polyhydric alcohol.   The manufacturing method according to any one of claims 1 to 5, wherein the heating temperature is 200 to 350 ° C. It has a plate-like shape with a major axis of 20 to 200 nm, a ratio of major axis to thickness of 1.5 to 30, a coercive force of 30 to 400 Oe, a saturation magnetization of 30 to 100 emu / g, and a squareness ratio of a magnetic hysteresis curve but (without SiO ₂ film on the surface of the proviso particles) cancer cautery ferromagnetic iron oxide particles characterized by having a magnetic property is 0.20 to 0.50.   The ferromagnetic iron oxide particles for cancer ablation treatment according to claim 7, wherein the iron oxide is any one of magnetite, gamma iron oxide, and iron oxide in an intermediate state between magnetite and gamma iron oxide.   The ferromagnetic iron oxide particles for treating cancer ablation according to claim 7 or 8, wherein the surface of the particles is modified with a surface modifier. It has a plate-like shape with a major axis of 20 to 200 nm, a ratio of major axis to thickness of 1.5 to 30, a coercive force of 30 to 400 Oe, a saturation magnetization of 30 to 100 emu / g, and a squareness ratio of a magnetic hysteresis curve Characterized in that ferromagnetic iron oxide particles for cancer ablation treatment having a magnetic property of 0.20 to 0.50 (but not having a SiO ₂ coating on the surface of the particles) are dispersed in an injection medium. A ferromagnetic iron oxide particle dispersion composition for treating cancer ablation.