JP2009280505A - Iron oxide nanoparticles - Google Patents

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JP2009280505A
JP2009280505A JP2008131160A JP2008131160A JP2009280505A JP 2009280505 A JP2009280505 A JP 2009280505A JP 2008131160 A JP2008131160 A JP 2008131160A JP 2008131160 A JP2008131160 A JP 2008131160A JP 2009280505 A JP2009280505 A JP 2009280505A
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iron oxide
oxide nanoparticles
magnetic field
frequency
thermotherapy
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Jayadewan Barachandoran
ジャヤデワン バラチャンドラン
Yasutake Hirota
泰丈 廣田
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Tohoku University NUC
Ferrotec Material Technologies Corp
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Ferrotec Corp
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Abstract

<P>PROBLEM TO BE SOLVED: To provide iron oxide nanoparticles suitable for thermotherapy for destruction of cancer cells according to applied magnetic field, frequency and viscosity, and to provide a method for determining particle diameters of the iron oxide nanoparticles suitable for the thermotherapy for destruction of the cancer cells according to the applied magnetic field, the frequency and the viscosity. <P>SOLUTION: The iron oxide nanoparticles are usable for the thermotherapy for the destruction of lesion cells by the heating to a prescribed temperature by generating the heat in a prescribed dispersion medium in the body by an external high-frequency magnetic field. The iron oxide nanoparticles are regulated so that the SAR value (specific absorption rate) defined by equation 1 under a condition of the external magnetic field of 600 kHz frequency and 3.2 kA/m magnetic field strength may be a calorific value required according to the lesion cells, that is ≥5.0 W/g and ≤28.3 W/g per unit time. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

本発明は、温熱療法に用いられる酸化鉄ナノ粒子であって、特に発熱特性及び磁気特性等の見地から決定された温熱療法に適した酸化鉄ナノ粒子に関するものである。   The present invention relates to iron oxide nanoparticles used for thermotherapy, and particularly to iron oxide nanoparticles suitable for thermotherapy determined from the viewpoint of exothermic characteristics and magnetic characteristics.

従来、酸化鉄粒子を癌組織近傍に配置(分散)して、外部から高周波磁場を印加して酸化鉄を発熱させることにより、癌組織を死滅させるいわゆる温熱療法が知られている(特許文献1〜4)。   Conventionally, so-called thermotherapy is known in which iron oxide particles are disposed (dispersed) in the vicinity of cancer tissue, and a high-frequency magnetic field is applied from the outside to cause iron oxide to generate heat, thereby killing the cancer tissue (Patent Document 1). ~ 4).

このような温熱療法は、癌細胞が正常細胞に比べて温まりやすく、かつ熱に弱いという性質を利用する治療法であり、より具体的には、病変部位を約40℃以上に加熱することにより、周辺の正常細胞には極力ダメージを与えないで癌細胞のみを死滅させることを企図するものである。   Such hyperthermia is a treatment method that utilizes the property that cancer cells tend to be warmer than normal cells and is weak against heat, and more specifically, by heating a lesion site to about 40 ° C. or higher. It is intended to kill only cancer cells without damaging peripheral normal cells as much as possible.

ここで、マグネタイト等に代表される酸化鉄粒子は高周波磁場中でヒステリシス損によって発熱し、このヒステリシス損による発熱は、酸化鉄粒子の粒子径に依存することが知られている。   Here, it is known that iron oxide particles typified by magnetite or the like generate heat due to hysteresis loss in a high-frequency magnetic field, and the heat generation due to this hysteresis loss depends on the particle diameter of the iron oxide particles.

より詳細には、粒子径が所定径より小さいと、マグネタイト等の酸化鉄粒子はヒステリシス損が生じないため発熱しない。一方において、粒子径が所定径より大きいと、粒子自身の磁気が原因で凝集が起こり、マグネタイトコロイドの溶媒分散性が損なわれる。   More specifically, when the particle diameter is smaller than the predetermined diameter, the iron oxide particles such as magnetite do not generate hysteresis because no hysteresis loss occurs. On the other hand, if the particle diameter is larger than the predetermined diameter, aggregation occurs due to the magnetism of the particles themselves, and the solvent dispersibility of the magnetite colloid is impaired.

以上のような意味において、温熱療法に適した酸化鉄粒子の粒子径には、所定の数値範囲が存在することが知られていた。
特許第3983843号公報 特開2006−307126号公報 特表2007−521109号公報 特開2007−256151号公報
In the above sense, it has been known that there is a predetermined numerical range for the particle diameter of iron oxide particles suitable for thermotherapy.
Japanese Patent No. 3983843 JP 2006-307126 A Special table 2007-521109 gazette JP 2007-256151 A

本発明は、以上の知見を踏まえ創作されたものである。すなわち本発明の目的は、印加磁場、周波数及び粘度に応じて、癌細胞を死滅させる温熱療法に適した酸化鉄ナノ粒子を提供することにある。   The present invention was created based on the above findings. That is, the objective of this invention is providing the iron oxide nanoparticle suitable for the thermotherapy which kills a cancer cell according to an applied magnetic field, a frequency, and a viscosity.

さらに本発明は、印加磁場、周波数及び粘度に応じて、癌細胞を死滅させる温熱療法に適した酸化鉄ナノ粒子の粒径の決定方法を提供することにある。   Furthermore, this invention is providing the determination method of the particle size of the iron oxide nanoparticle suitable for the thermotherapy which kills a cancer cell according to an applied magnetic field, a frequency, and a viscosity.

上記課題を解決するために、本発明者は、超常磁性マグネタイトナノ粒子の発熱メカニズムに関し、いわゆるネール緩和とブラウニアン緩和とに大別されることを見出し、この二つの緩和に関し、以下の点に着目した。   In order to solve the above-mentioned problems, the present inventors have found that the heat generation mechanism of superparamagnetic magnetite nanoparticles is roughly classified into so-called Neel relaxation and Brownian relaxation, and the following points are focused on these two relaxations. did.

第1に、この二つの緩和のバランスが、マグネタイトの粒子径に依存する点である。より詳細には、マグネタイトの粒子径が大きいほど、ブラウニアン緩和が支配的となる。
第2に、マグネタイトナノ粒子が置かれる環境の粘度と発熱との関係について、粘度が高いほどブラウン緩和による発熱が減少する点である。
First, the balance between the two relaxations depends on the particle size of the magnetite. More specifically, the larger the magnetite particle size, the more dominant the Brownian relaxation.
Secondly, regarding the relationship between the viscosity of the environment where the magnetite nanoparticles are placed and the heat generation, the higher the viscosity, the lower the heat generated by Brownian relaxation.

第3に、ブロッキング温度の高温側へのシフトと粒子径との関係について、マグネタイトの粒子径が大きいほど、周波数の変化によるブロッキング温度の高温側へのシフトが抑制される点である。   Thirdly, regarding the relationship between the shift of the blocking temperature to the high temperature side and the particle size, the larger the particle size of the magnetite, the more the shift of the blocking temperature to the high temperature side due to the frequency change is suppressed.

特に、第1および第2の点に関連して、磁気緩和機構が発熱特性に与える影響について、以下の式で定義されるSAR値を用いて、その影響、とりわけ分散媒の粘度の影響について評価を行い、適正な数値範囲を見出した。   In particular, in relation to the first and second points, the influence of the magnetic relaxation mechanism on the heat generation characteristics is evaluated using the SAR value defined by the following equation, particularly the influence of the viscosity of the dispersion medium. And found an appropriate numerical range.

Figure 2009280505
(ここで、Cは:分散媒および酸化鉄ナノ粒子の各比熱、mは:分散媒および酸化鉄ナノ粒子の各重量、△T/△tは:初期温度変化率)
Figure 2009280505
(Where C is the specific heat of the dispersion medium and iron oxide nanoparticles, m is the weight of the dispersion medium and iron oxide nanoparticles, and ΔT / Δt is the initial temperature change rate)

本発明者は、以上の知見に基いて以下の発明を創作した。
(1)外部高周波磁場により、体内における所定の分散媒中で発熱させて、病変細胞を所定温度まで加熱することにより死滅させる温熱療法に利用される酸化鉄ナノ粒子であって、周波数600kHz、磁界強度3.2kA/mの外部磁場の条件下において、下記式で定義されるSAR値が、病変細胞に応じて要求される発熱量すなわち単位時間当たり5.0W/g以上28.3W/g以下となることを特徴とする酸化鉄ナノ粒子である。
The present inventor has created the following invention based on the above knowledge.
(1) Iron oxide nanoparticles that are used in thermotherapy to cause heat generation in a predetermined dispersion medium in the body by an external high-frequency magnetic field and kill the diseased cells by heating to a predetermined temperature, with a frequency of 600 kHz and a magnetic field Under the condition of an external magnetic field with an intensity of 3.2 kA / m, the SAR value defined by the following formula is the calorific value required according to the diseased cell, that is, 5.0 W / g or more and 28.3 W / g or less per unit time It is an iron oxide nanoparticle characterized by becoming.

Figure 2009280505
ここでSAR値が28.3を超えると、酸化鉄ナノ粒子のブラウニアン緩和が支配的になるので、局所的な作用(血液等による粘度の影響、臓器等への粒子の固着)によって発熱が抑制される可能性がある。
Figure 2009280505
Here, when the SAR value exceeds 28.3, the Brownian relaxation of the iron oxide nanoparticles becomes dominant, so that the heat generation is suppressed by local action (the influence of the viscosity due to blood, etc., the adhesion of the particles to the organ, etc.). There is a possibility that.

一方、SAR値が5.0未満の場合は、酸化鉄ナノ粒子を大量に入れないと所望の発熱量が生じないという可能性がある。また磁場をかける時間も相対的に長くなり人体への悪影響も懸念される。   On the other hand, when the SAR value is less than 5.0, there is a possibility that a desired calorific value does not occur unless a large amount of iron oxide nanoparticles are added. In addition, the time for applying the magnetic field is relatively long, and there is a concern about adverse effects on the human body.

(2)前記酸化鉄ナノ粒子が、主にマグネタイトによって形成されていることを特徴とする上記(1)記載の酸化鉄ナノ粒子である。
マグネタイトが主成分であれば、他の酸化鉄ナノ粒子との混合物であっても良い。例えば、γFe23及びFe34の混合物であっても良い。
(2) The iron oxide nanoparticles according to (1), wherein the iron oxide nanoparticles are mainly formed of magnetite.
If magnetite is the main component, it may be a mixture with other iron oxide nanoparticles. For example, a mixture of γFe 2 O 3 and Fe 3 O 4 may be used.

(3)前記酸化鉄ナノ粒子の粒径が、11nm以上14nm以下であることを特徴とする上記(1)または(2)に記載の酸化鉄ナノ粒子である。
ここでいう酸化鉄ナノ粒子の粒径は、個体における粒径であっても良いし、複数の酸化鉄ナノ粒子の集合体の場合は、その平均粒子径であっても良い。
なお、平均粒子径の分布範囲が狭い方が、温度制御コントロールをはじめとする実用状況での管理が容易で、かつ発熱効率も良好である。
(3) The iron oxide nanoparticles according to (1) or (2), wherein the iron oxide nanoparticles have a particle size of 11 nm or more and 14 nm or less.
The particle diameter of the iron oxide nanoparticles referred to here may be the particle diameter of an individual, or may be the average particle diameter in the case of an aggregate of a plurality of iron oxide nanoparticles.
In addition, the one where the distribution range of the average particle diameter is narrower is easier to manage in practical situations such as temperature control, and the heat generation efficiency is better.

本発明者は、発熱特性に優れた酸化鉄ナノ粒子を見出す上で、磁気緩和機構が発熱特性に与える影響について考察した。
すなわち、酸化鉄ナノ粒子の発熱機構として、ネール緩和とブラウニアン緩和という概念がある。ここでネール緩和とは磁気モーメントの回転による緩和であり、以下の式で表わされる。
The present inventor considered the influence of the magnetic relaxation mechanism on the heat generation characteristics in finding iron oxide nanoparticles having excellent heat generation characteristics.
That is, there is a concept of Neel relaxation and Brownian relaxation as a heat generation mechanism of iron oxide nanoparticles. Here, Neel relaxation is relaxation by rotation of a magnetic moment, and is expressed by the following equation.

Figure 2009280505
他方、ブラウニアン緩和は磁性粒子の回転による緩和であり、以下の式で表わされる。
Figure 2009280505
On the other hand, Brownian relaxation is relaxation caused by rotation of magnetic particles, and is expressed by the following equation.

Figure 2009280505
Figure 2009280505

酸化鉄ナノ粒子の発熱特性において、In−Vitroの場合と実際に温熱療法において使用される場合とで発熱量に差があることが知られていた。
これは温熱療法においては、酸化鉄ナノ粒子が体内に取り込まれることからゲル中にお
いて適正な発熱量を得る必要がある。そのためには発熱特性においてブラウニアン緩和が支配的な酸化鉄ナノ粒子の場合は、高粘度の媒体中においては発熱量が減少する可能性がある。
In the exothermic property of iron oxide nanoparticles, it has been known that there is a difference in calorific value between the case of In-Vitro and the case where it is actually used in thermotherapy.
This is because in thermotherapy, iron oxide nanoparticles are taken into the body, so that it is necessary to obtain an appropriate calorific value in the gel. For this purpose, in the case of iron oxide nanoparticles in which the Brownian relaxation is dominant in the heat generation characteristics, there is a possibility that the heat generation amount is reduced in a high viscosity medium.

次に本発明で用いられる酸化鉄ナノ粒子について説明する。
本発明の酸化鉄ナノ粒子としては、磁性粒子として酸素と鉄とを含有する酸化鉄であれば良い。例えば、マグヘマイトと呼ばれるγ酸化鉄等のフェライト、マグネタイト、コバルトフェライト、バリウムフェライトが挙げられる。これらの中で特に好ましくはマグネタイトである。
ここで発熱量は以下の式で表わされる。
Next, the iron oxide nanoparticles used in the present invention will be described.
The iron oxide nanoparticles of the present invention may be iron oxide containing oxygen and iron as magnetic particles. Examples thereof include ferrite such as γ iron oxide called maghemite, magnetite, cobalt ferrite, and barium ferrite. Among these, magnetite is particularly preferable.
Here, the calorific value is expressed by the following equation.

Figure 2009280505
ここで、P:発熱量、μ0:真空下における透磁率、χ'':交流磁界率の虚数部、f:
周波数、H0:磁界強度を表わす。
Figure 2009280505
Here, P: calorific value, μ 0 : permeability under vacuum, χ ″: imaginary part of AC magnetic field ratio, f:
Frequency, H 0 : represents magnetic field strength.

酸化鉄ナノ粒子について、マグヘマイト、マグネタイト、コバルトフェライト、バリウムフェライトの4種類を使って、夫々の発熱量及び最大発熱特性を示す粒子径を上記式より求めた。
分散安定性の見地からみると酸化鉄ナノ粒子としては、マグネタイトが最適であることが分った。
About the iron oxide nanoparticle, the particle diameter which shows each calorific value and the maximum heat generation characteristic was calculated | required from the said type | formula using four types, maghemite, magnetite, cobalt ferrite, and barium ferrite.
From the viewpoint of dispersion stability, it was found that magnetite is optimal as the iron oxide nanoparticles.

本発明で用いられる酸化鉄ナノ粒子の製造方法について説明する。
酸化鉄ナノ粒子は、一般的に粉砕法、共沈法、蒸着法あるいは他の類似の方法で作製される。中でも生産性の観点からは、通常共沈法が好ましい。
A method for producing iron oxide nanoparticles used in the present invention will be described.
Iron oxide nanoparticles are generally produced by a pulverization method, a coprecipitation method, a vapor deposition method, or other similar methods. Among them, the coprecipitation method is usually preferable from the viewpoint of productivity.

(製造方法)
具体的な共沈法による粒子製造方法をマグネタイトの例で述べる。以下の製造方法は一例であって本発明の酸化鉄ナノ粒子を限定するものではない。
まず、13.0gの硫酸第一鉄7水和物と24.0gの塩化第二鉄6水和物を水に溶解し、全溶液量は水で70ccに調整する。30ccの28%アンモニア水が塩鉄溶液に加えられ、Fe34粒子を沈殿させる。
(Production method)
A specific method for producing particles by coprecipitation will be described with an example of magnetite. The following production method is an example and does not limit the iron oxide nanoparticles of the present invention.
First, 13.0 g of ferrous sulfate heptahydrate and 24.0 g of ferric chloride hexahydrate are dissolved in water, and the total amount of the solution is adjusted to 70 cc with water. 30 cc of 28% aqueous ammonia is added to the salt iron solution to precipitate Fe 3 O 4 particles.

次に2.1gのオレイン酸と70℃に熱せられた27ccの3%アンモニア水から成るオレイン酸溶液を用意する。かかるオレイン酸溶液を前記Fe34粒子の懸濁液に加え、オレイン酸イオンで粒子を被覆した状態で約1時間ほど静置する。
次に30ccのヘプタンがオレイン酸で覆われた粒子の懸濁液に注がれ、懸濁液全体を攪拌し、放置する。オレイン酸で被覆された粒子は、ヘプタン中に解膠し、ヘプタンを分散媒とした磁性流体を200ccのビーカーに入れる。
このようにしてマグネタイトのナノ粒子を得ることができる。
Next, an oleic acid solution consisting of 2.1 g of oleic acid and 27 cc of 3% aqueous ammonia heated to 70 ° C. is prepared. Such an oleic acid solution is added to the suspension of Fe 3 O 4 particles, and the mixture is allowed to stand for about 1 hour while the particles are covered with oleate ions.
Next, 30 cc of heptane is poured into the suspension of particles covered with oleic acid and the entire suspension is stirred and allowed to stand. The particles coated with oleic acid are peptized in heptane, and a magnetic fluid containing heptane as a dispersion medium is put into a 200 cc beaker.
In this way, magnetite nanoparticles can be obtained.

上記の製造方法によってマグネタイトのナノ粒子を得た。この際、イオン添加直後及び反応途中のpHを変動することによって、ナノ粒子の粒子径と粒分布を制御した。
試料No.1は平均粒子径12nm、試料No.2は13nm、試料No.3は14nmであ
った。試料No.3のナノ粒子は従来品である。
上記試料No.1〜3における発熱特性を、周波数600kHz、磁界強度3.2kA/mの外部磁場の条件下において計測したところ図1のグラフが得られた。
Magnetite nanoparticles were obtained by the above production method. At this time, the particle size and particle distribution of the nanoparticles were controlled by changing the pH immediately after the addition of ions and during the reaction.
Sample No. 1 had an average particle diameter of 12 nm, sample No. 2 had 13 nm, and sample No. 3 had 14 nm. The nanoparticles of sample No. 3 are conventional products.
When the heat generation characteristics of the samples No. 1 to 3 were measured under the conditions of an external magnetic field having a frequency of 600 kHz and a magnetic field strength of 3.2 kA / m, the graph of FIG. 1 was obtained.

図1より明らかなように最も発熱特性の良いものは、試料No.2のナノ粒子であった。最も発熱特性の悪いものは試料No.3のナノ粒子であった。2つの試料における下記の式に基いてSAR値を求めたところ、試料No.2は15.7[W/g]であり、試料No.3は4.6[W/g]であった。

Figure 2009280505
As is clear from FIG. 1, the sample having the best heat generation characteristics was the sample No. 2 nanoparticles. The sample with the lowest exothermic property was the sample No. 3 nanoparticles. When the SAR values of the two samples were determined based on the following formula, the sample No. 2 was 15.7 [W / g] and the sample No. 3 was 4.6 [W / g].
Figure 2009280505

上記の製造方法によって粒径の異なるマグネタイトのナノ粒子を2種類製造した。試料No.4は平均粒子径が12.5nmであり、試料No.5は平均粒子径が15.7nmであった。   Two types of magnetite nanoparticles having different particle diameters were produced by the production method described above. Sample No. 4 had an average particle size of 12.5 nm, and Sample No. 5 had an average particle size of 15.7 nm.

試料No.4及び試料No.5のナノ粒子を、比熱4.2J/K・gの水に分散させた場合と、比熱2.8J/K・gのハイドロゲルに分散させた場合であって、周波数600kHz、磁界強度3.2kA/mの外部磁場の条件下において発熱特性を計測した。図2は試料No.4における水、ハイドロゲル中の測定結果を示したグラフである。図3はNo.5における水、ハイドロゲル中の測定結果を示したグラフである。   Sample No. 4 and sample No. 5 nanoparticles dispersed in water with a specific heat of 4.2 J / K · g and when dispersed in a hydrogel with a specific heat of 2.8 J / K · g. The heat generation characteristics were measured under conditions of an external magnetic field having a frequency of 600 kHz and a magnetic field strength of 3.2 kA / m. 2 is a graph showing the measurement results in water and hydrogel of sample No. 4. 3 is a graph showing the measurement results in water and hydrogel in No. 5.

図2及び3から明らかなように、試料No.5の方がNo.4よりハイドロゲル中における発熱特性に劣っていることが分る。
またマグネタイトの比熱を0.92J/K・gとし、初期温度変化率を60秒の時のグラフの傾斜から計算し、SAR値を求めると以下の表1、表2の結果となった。

Figure 2009280505
Figure 2009280505
As apparent from FIGS. 2 and 3, it can be seen that Sample No. 5 is inferior to No. 4 in heat generation characteristics in the hydrogel.
Further, when the specific heat of magnetite was 0.92 J / K · g, the initial temperature change rate was calculated from the slope of the graph at 60 seconds, and the SAR value was obtained, the results shown in Tables 1 and 2 below were obtained.
Figure 2009280505
Figure 2009280505

上記の結果より平均粒径15.7nmの試料No.5は、ブラウニアン緩和の抑制によるSAR値の低下が起こっていると考えられる。また粒子間の磁気的相互作用によるSAR値の低下、すなわち自由な回転が可能な水分散媒中のナノ粒子に比較して、ハイドロゲル中ではナノ粒子が固定されてしまい、粒子間の磁気的相互作用が強くなり、磁気緩和及び発熱特性に影響を与えたものと考えられる。
試料No.4のナノ粒子は、ネール緩和が支配的であるため、粒子間の時期的相互作用(磁気的相互作用)は小さく、ブラウニアン緩和による発熱への関与が少ないと考えられる。
From the above results, it is considered that the sample No. 5 having an average particle diameter of 15.7 nm has a decrease in the SAR value due to suppression of Brownian relaxation. In addition, the SAR value is lowered by the magnetic interaction between particles, that is, the nanoparticles are fixed in the hydrogel as compared with the nanoparticles in the aqueous dispersion medium that can freely rotate, and the magnetic force between the particles is reduced. It is thought that the interaction became stronger and affected the magnetic relaxation and heat generation characteristics.
In the nanoparticle of sample No. 4, since the Neel relaxation is dominant, the temporal interaction (magnetic interaction) between the particles is small, and it is considered that the heat generation due to the Brownian relaxation is small.

次にブロック温度とSAR値の関係についての観測結果を示す。
酸化鉄ナノ粒子のような粒子サイズでは超常磁性の磁気特性を有するとされているが、実際には交流磁界の周波数の上昇と共に磁気モーメントの緩和に遅れが生じ、微小のヒステリシスを生じることが知られている。
ここで、ブロッキング温度は超常磁性が観測され始める温度であり、その温度以下では、磁気モーメントの緩和時間が観測時間より長いことからヒステリシスを生じることが知
られている。
Next, observation results regarding the relationship between the block temperature and the SAR value are shown.
It is said that particle sizes such as iron oxide nanoparticles have superparamagnetic properties, but in reality it is known that the relaxation of the magnetic moment is delayed with the increase of the frequency of the alternating magnetic field, resulting in minute hysteresis. It has been.
Here, it is known that the blocking temperature is a temperature at which superparamagnetism starts to be observed, and below that temperature, a hysteresis occurs because the relaxation time of the magnetic moment is longer than the observation time.

従って、ブロッキング温度は観測時間である交流磁界の周波数によって異なる。観測時間の減少(交流磁界の周波数の上昇)と共にブロッキング温度は高温側にシフトする。
実際には、最大で10kHzまでの測定が可能だが、600kHzのブロッキング温度の測定は困難であり、10kHz以下で行われた測定結果をもとに予測する必要があった。
そこで上記実施例2で得られた試料No.5において観測時間とその観測時間でのブロッキング温度の逆数のプロットから実験条件である600kHzでのブロッキング温度を予測した。
Therefore, the blocking temperature varies depending on the frequency of the alternating magnetic field, which is the observation time. As the observation time decreases (the frequency of the alternating magnetic field increases), the blocking temperature shifts to the higher temperature side.
Actually, it is possible to measure up to 10 kHz, but it is difficult to measure the blocking temperature of 600 kHz, and it is necessary to make a prediction based on the measurement result performed at 10 kHz or less.
Therefore, in the sample No. 5 obtained in Example 2 above, the blocking temperature at 600 kHz, which is the experimental condition, was predicted from the plot of the observation time and the reciprocal of the blocking temperature at the observation time.

また、各サンプルのブロッキング温度とSARとの関係を見た結果、ブロッキング温度の上昇と共にSARも上昇した。
しかし、ブロッキング温度は室温より高くなった場合、度合によって、ネール緩和の遅れによるヒステリシス損失だけではなく、ブラウニアン緩和にヒステリシス損失も加わる。
上記観測の観測結果を、図4〜6図に示す。図4は、交流磁化率測定結果(L−H)を示すグラフであり、図5は600kHzにおけるブロッキング温度の予測を示すグラフであり、図6はブロッキング温度とSARとの関係を示すグラフである。
Moreover, as a result of observing the relationship between the blocking temperature of each sample and the SAR, the SAR increased as the blocking temperature increased.
However, when the blocking temperature is higher than room temperature, depending on the degree, not only hysteresis loss due to delay of Neel relaxation, but also hysteresis loss is added to Brownian relaxation.
The observation results of the above observation are shown in FIGS. FIG. 4 is a graph showing AC magnetic susceptibility measurement results (LH), FIG. 5 is a graph showing the prediction of the blocking temperature at 600 kHz, and FIG. 6 is a graph showing the relationship between the blocking temperature and SAR. .

実施例1(試料No.1〜3)における発熱測定結果を示すグラフである。It is a graph which shows the heat_generation | fever measurement result in Example 1 (sample No. 1-3). 実施例2(試料No.4)における発熱測定結果を示すグラフである。It is a graph which shows the heat_generation | fever measurement result in Example 2 (sample No. 4). 実施例2(試料No.5)における発熱測定結果を示すグラフである。It is a graph which shows the heat_generation | fever measurement result in Example 2 (sample No. 5). 交流磁化率測定結果(L−H)を示すグラフである。It is a graph which shows an alternating current magnetic susceptibility measurement result (LH). 600kHzにおけるブロッキング温度の予測を示すグラフである。It is a graph which shows prediction of the blocking temperature in 600 kHz. ブロッキング温度とSARとの関係を示すグラフである。It is a graph which shows the relationship between blocking temperature and SAR.

Claims (3)

外部高周波磁場により、体内における所定の分散媒中で発熱させて、病変細胞を所定温度まで加熱することにより死滅させる温熱療法に利用される酸化鉄ナノ粒子であって、周波数600kHz、磁界強度3.2kA/mの外部磁場の条件下において、下記式で定義されるSAR値が、病変細胞に応じて要求される発熱量すなわち単位時間当たり5.0W/g以上28.3W/g以下となることを特徴とする酸化鉄ナノ粒子。
Figure 2009280505
(ここで、Ci:分散媒および酸化鉄ナノ粒子の各比熱、mi:分散媒および酸化鉄ナノ粒子の各重量、△T/△t:初期温度変化率)
2. Iron oxide nanoparticles that are used in thermotherapy to generate heat in a predetermined dispersion medium in the body by an external high-frequency magnetic field and kill the diseased cells by heating to a predetermined temperature, with a frequency of 600 kHz and a magnetic field strength of 3. Under the condition of an external magnetic field of 2 kA / m, the SAR value defined by the following formula should be a calorific value required for a diseased cell, that is, 5.0 W / g or more and 28.3 W / g or less per unit time. Iron oxide nanoparticles characterized by.
Figure 2009280505
(Where Ci: specific heat of dispersion medium and iron oxide nanoparticles, mi: weight of dispersion medium and iron oxide nanoparticles, ΔT / Δt: initial temperature change rate)
前記酸化鉄ナノ粒子が、主にマグネタイトによって形成されていることを特徴とする請求項1記載の酸化鉄ナノ粒子。 The iron oxide nanoparticles according to claim 1, wherein the iron oxide nanoparticles are mainly formed of magnetite. 前記酸化鉄ナノ粒子の粒径が、11nm以上14nm以下であることを特徴とする請求項1または2に記載の酸化鉄ナノ粒子。 The iron oxide nanoparticles according to claim 1 or 2, wherein the iron oxide nanoparticles have a particle size of 11 nm or more and 14 nm or less.
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Cited By (2)

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Publication number Priority date Publication date Assignee Title
JP2013513543A (en) * 2009-12-15 2013-04-22 コロロッビア イタリア ソシエタ ペル アチオニ Magnetite in the form of nanoparticles
JP2017205335A (en) * 2016-05-19 2017-11-24 中松 義郎 System of treating duct carcinoma or the like

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013513543A (en) * 2009-12-15 2013-04-22 コロロッビア イタリア ソシエタ ペル アチオニ Magnetite in the form of nanoparticles
JP2017014102A (en) * 2009-12-15 2017-01-19 コロロッビア イタリア ソシエタ ペル アチオニ Magnetic iron ore in nanoparticle form
JP2017205335A (en) * 2016-05-19 2017-11-24 中松 義郎 System of treating duct carcinoma or the like
US11000408B2 (en) 2016-05-19 2021-05-11 Yoshiro Sir NakaMats Treatment system for cancer etc
US11291583B2 (en) 2016-05-19 2022-04-05 Sir Dr. Yoshiro Nakamats Treatment system for cancer etc

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