JP4649406B2 - 改善された磁気性質を有する磁性ナノ粒子 - Google Patents

改善された磁気性質を有する磁性ナノ粒子 Download PDF

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JP4649406B2
JP4649406B2 JP2006518157A JP2006518157A JP4649406B2 JP 4649406 B2 JP4649406 B2 JP 4649406B2 JP 2006518157 A JP2006518157 A JP 2006518157A JP 2006518157 A JP2006518157 A JP 2006518157A JP 4649406 B2 JP4649406 B2 JP 4649406B2
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magnetic
metal oxide
magnetic nanoparticles
polymer
magnetic nanoparticle
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JP2007538380A (ja
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テラー、ヨアヒム
ヴェストパール、フリッツ
グリュットナー、コルドゥラ
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ミクロモート パルティケルテヒノロギー ゲーエムベーハー
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Description

【技術分野】
【０００１】
本発明は、金属酸化物−ポリマー複合体から構成される磁性ナノ粒子に関する。
【背景技術】
【０００２】
ナノメータ範囲の径を有する磁性成分粒子については、既に、技術的に確立された一連の用途が存在する。例えば、この種の粒子は、分子生物学の用途において、細胞、細胞成分、核酸、酵素、抗体、タンパク質およびペプチドの分離、固定および精製に使用でき、細胞生物学において、食作用実験に使用でき、臨床化学において、診断アッセイまたは治療医薬品の成分として使用でき、臨床診断において、対照剤、放射性核種担体または薬剤担体として使用でき、生化学および工業化学において、分子認知現象および不均一触媒現象の実験のために使用できる。
【０００３】
ポリマーを被覆した多数の金属酸化物粒子が、１９８０年代の中頃から、磁界中における生物学的使用に関して記載されている。特に、磁化可能な２００ｎｍ未満のナノ粒子は、細胞、細胞成分、バイオ活性分子および放射性核種の輸送および分離のための新規の可能性を開拓し（ＵＳ２００３／００９９９５４ ＭＩＬＴＥＮＹＩ；ＷＯ０１／１７６６２ ＺＢＯＲＯＷＳＫＩ；ＷＯ０２／４３７０８ ＡＬＥＸＩＯＵ），コントラストを与える磁気撮像・診断法におけるマーキングとしての使用のための新規の可能性を開拓し（ＵＳ２００３／００９２０２９Ａ１ ＪＯＳＥＰＨＳＯＮ；ＷＯ０１／７４２４５ ＪＯＨＡＮＳＳＯＮ；ＵＳ５４２７７６７ ＫＲＥＳＳＥ），生きた細胞の機械的制御（ＤＥ１００２０３７６Ａ１ ＫＯＣＨ）および熱的制御（ＵＳ６５４１０３９ ＬＥＳＥＮＩＡＫ）のための新規の可能性を開拓し、従って、その適用関連の性質は、定常的に改善されている。すべての使用において共通に、磁化可能な金属酸化物を、５ｎｍ〜５００ｎｍの大きさの複合粒子（Kompositpartikeln）になるよう、バイオ適合性ポリマーコーティングと結合して、コロイド的に安定の水性サスペンジョンを形成する。この場合、コーティング材料は、生物学的材料との交互作用を排除し、生きた細胞と良好な適合性を実現でき、かつ生きた有機体における新陳代謝プロセスに影響を与えなければならず、あるいは、生化学的活性物質による適切な作用によって、表面における選択的結合を実現できるか、管理して封入された物質を遊離しなければならない。この場合、複合粒子の磁化可能な成分によって、外部の磁界とのエネルギ的交互作用を利用する。このような粒子は、磁界中において、磁気的性質に依存して配向され、立体的な磁界勾配に対応して移動され、外部磁界の時間的変化に応答する。金属酸化物微粒子として鉄酸化物微結晶を調製するため、多数の方法が記載されており、例えば、高温における焼結、以降の機械的粉砕、溶液からの真空条件下のクラスタ形成または湿式化学合成を行う。鉄酸化物の沈殿は、非水性条件下で行うことができ（ＵＳ４６７７０２７ ＰＯＲＡＴＨ），次いで、水性条件に移行できるか（ＵＳ５１６０７２５ ＰＩＬＧＲＩＭ）、或いは専ら水溶液中で行うことができる（ＵＳ４３２９２４１ ＭＡＳＳＡＲＴ）。毒物学的理由から、生物学的用途には、水性処方を使用する（ＵＳ４１０１４３５ ＨＡＳＥＧＡＷＡ）。鉄酸化物微結晶の湿式化学合成は、ポリマー成分による被覆に先行してでき（コア・シェル法）、或いはポリマーの存在下で行うことができる（単一ポット法）。コア・シェル法の場合、鉄酸化物に安定剤を添加する必要がある。なぜならば、鉄酸化物は、水性サスペンジョン中で、集合体を形成する傾向を示すからである。安定剤としては、両親媒性（amphiphil）物質（ＷＯ０１／５６５４６ ＢＡＢＩＮＣＯＶＡ）または表面に帯電した付加的ナノ粒子（ＵＳ４２８０９１８ ＨＯＭＯＬＡ）が考えられる。しかしながら、安定剤としての表面活性物質は、表面の化学的官能化の可能性を大きく制限する。現在、一般に、主として、単一ポット法にもとづき調製した磁化可能な鉄含有ナノ複合粒子が、その物理的、化学的性質および医学的用途について薬学的／生薬的安定性にもとづき、受入れられている。単一ポット法の場合、溶液からの核形成および結晶成長時に安定化のため、鉄酸化物の形成中、直接に被覆ポリマーを使用する。汎用される被覆材料の１つは、デキストランの各種の変形ないし修飾形態である。しかしながら、他の多糖類（例えば、アラビノガラクタン，デンプン、グリコースアミノグリカンまたはタンパク質）も使用される（ＵＳ６５７６２２１ ＫＲＥＳＳＥ）。たぶん最も簡単な方法は、デキストランの存在下の鉄（ＩＩ）塩および鉄（ＩＩＩ）塩の沈殿である（ＵＳ４４５２７７３ ＭＯＬＤＡＹ）。超音波の使用および以降の貫流法における熱処理による方法が使用される（ＵＳ４８２７９４５ ＧＲＯＭＡＮ）。製品の品質は、磁気選別によって更に改善できる（ＷＯ９０／０７３８０ ＭＩＬＴＥＮＹＩ）。概ね、安定剤としてアンフィフィル物質の使用下における十分なカプセル化／被覆によって、複合粒子に対する生物学的系の挙動を本質的に改善できる（ＵＳ５５４５３９５ ＴＯＵＲＮＩＥＲ，ＥＰ０２７２０９１ ＥＬＥＹ）。
【０００４】
注入（注射）可能な液体としての高分散性の水系を調製するため、各種の安定剤以外に、支援のため、特殊な均質化系を使用する。このような方法は、例えば、ロータ・ステータ均質化（Homogenisierung）および高圧均質化である。特に大きな機械的エネルギ供与が、液体ジェット高圧均質化装置（ホモジナイザ）または液体・スロット・ノズル均質化装置によって達成され（マイクロ流動化技術）、これは、特に、リポソームの調製に利用されるが（ＵＳ５６３５２０６ ＧＡＮＴＥＲ），他の事例においても、注入可能な作用物質処方の調製を簡単化する（ＵＳ５５９５６８７ ＲＡＹＮＯＬＤＳ）。制御された融合に続いてゾルとしての酸化物成分を非水性成分中に含むエマルジョン中で乾燥することによって酸化ナノ複合粒子を調製するための高圧均質化装置の使用は、触媒材料（ＵＳ５３０４３６４ ＣＯＳＴＡ）、電子写真のトナー粒子、セラミック粉体、フェルト材料、噴霧層、作用物質担体またはイオン交換樹脂の工業生産に関連して記載されている（ＵＳ５５８０６９２ ＬＯＦＦＴＵＳ）。
【特許文献１】
ＵＳ４４５２７７３
【特許文献２】
ＷＯ９０／０７３８０
【発明の開示】
【発明が解決しようとする課題】
【０００５】
２００ｎｍ未満のサイズ範囲の上述のすべてのタイプの磁性粒子は、概ね、煩瑣ないし大掛かりな分離法（例えば、高勾配磁気分離）を介してのみ濃縮または固定できるに過ぎない。
【０００６】
他方、生命科学において、多数の磁性粒子応用が、既に存在し、これらは、永久磁石による分離工程によって本質的に有効に実施できるものであるか、または他の理由から粒子の高い磁気移動性を必要とするものである。
【０００７】
従って、本発明の課題は、小さい磁界強度において十分に高度の磁化を達成する磁性ナノ粒子を提供することにある。
【課題を解決するための手段】
【０００８】
この課題は、金属の重量割合が５０％以上であり且つ流体力学的径が２００ｎｍ未満である金属酸化物およびポリマーから構成される磁性ナノ粒子を、成分および担体から、ＰＨ＞７を有する水性担持媒体中で、５００ｂａｒ以上の高圧均質化によって形成することによって、解決される。
【０００９】
上記の磁性ナノ粒子は、更に、該粒子が、小さい（特に５０Ｏｅ未満の）磁界強度において、使用した金属酸化物よりも比較的大きい磁気モーメントを有することを特徴とする。
【００１０】
このような磁性ナノ粒子は、磁気リポソームの場合の如く、両親媒性分子によって構造が形成（strukturiert）されず、強磁性流体において、通常、行われる如く、界面活性剤によって安定化されるものでもない。むしろ上記粒子は、水中および水溶液中で、外部の磁界の作用を要することなく、長時間安定なコロイドを形成する。また、こうして形成された磁性ナノ粒子は、永久磁石によって分離可能である。
【００１１】
使用される金属酸化物は、特に、鉄酸化物（例えば、マグネタイト（Ｆｅ3Ｏ4）またはマグヘマイト（Ｆｅ2Ｏ3）またはこれらから得られる混合相）である。鉄酸化物は、他の２価または３価の金属イオン（例えば、Ｃａ2+，Ｂａ2+，Ｚｎ2+，Ｃｏ2+，Ｃｏ3+，Ｃｒ3+，Ｔｉ3+，Ｍｏ2+，Ｍｎ2+およびＣｕ2+）を含むことができる。
【００１２】
使用したポリマーは、合成的ポリマーの範囲から得ることができる。これについて、基本的に、金属イオンに対する結合的交互作用をすることができる異原子または官能基を含むポリマー（特に、ポリオール、ポリアミン、ポリエーテル、ポリエステル、ポリアミド、これらから誘導した誘導体、コポリマーおよびブレンド）を使用する。
【００１３】
他方、ポリマーは、バイオポリマーのグループおよび、この場合特に、多糖類の範囲から選択できる。天然多糖類も、誘導された多糖類も対象となる。多糖類のうち、一連の代表的多糖類は、重金属イオンに対して、特に、鉄イオンにも、優れた親和性を有する。
【００１４】
上記の代表的多糖類には、更に、受ける品質変動が、他の天然多糖類（例えば、デンプン）よりも少なく、従って、粒子チャージの再現性に重要な利点を有するデキストランも含まれる。デキストランの誘導体生成操作を様々な態様で実施できる。かくして、それ自体は公知の方法にもとづき、官能基（ＣＯＯＨ，ＮＨ2，．．．等），官能基（ポリエチレングリコール・ベースのＣＯＯＨ基またはＮＨ2基）を含むスペーサーまたは生化学的に重要な基礎構造体（Substrukturen オリゴヌクレチド、核酸、ペプチド、タンパク質、抗体および酵素）を導入できる。しかしながら、例えば、放射性同位体の固定のための、金属選択性キレートまたは薬学的作用物質を結合するため、デキストランの誘導体生成を利用することもできる。
【００１５】
本発明に係る磁性ナノ粒子の調製技術として、Ｍ−１１０Ｙタイプのマイクロフルイダイザ（Microfluidizer）TMを使用した高圧均質化が有効であることが実証されている。成分である金属酸化物およびポリマーは、担持媒体（多くの場合、水を使用する）中において、５００ｂａｒ以上の圧力で、特に５００〜１２００ｂａｒの範囲の圧力下で大きい剪断力を使用して処理（超均質化）する。この方法は、超均質化中に始めて対応する金属塩または金属水酸化物から金属酸化物をインシトゥで（in situ、そのままの状態ないしその場で）形成することによって、改善することもできる。この場合、アルカリ性担媒体（例えば、アンモニア水溶液）を使用する。
【００１６】
驚くべきことには、媒体中で成分である金属酸化物およびポリマーを高圧均質化（ホモジナイズ）することによって、２００ｎｍ未満の径範囲のコロイド的に安定な磁性粒子集群が得られるのみならず、形成された磁性ナノ粒子が、５０Ｏｅ未満の小さい磁界強度において、出発材料として使用した金属酸化物について測定した磁気モーメントよりも大きい磁気モーメントを与えると云うことを確認できた（図１）。
【００１７】
磁気移動度に対する改善された磁気的性質の作用は、本発明にもとづき調製した磁性ナノ粒子について求めた数値を従来の超常磁性鉄酸化物粒子（ＳＰＩＯ）と比較すれば明らかであろう（図２）。実施例１〜５にもとづき得られた磁性ナノ粒子は、例外なく、対比すべきＳＰＩＯ粒子（ＵＳ４４５２７７３と同様．粒子径：１００ｎｍ）よりも本質的に大きい磁気移動度を有する。
【発明の効果】
【００１８】
本発明により、２００ｎｍ未満のサイズで、小さい磁界強度において十分に高度な磁化を達成する磁性ナノ粒子を形成でき、これらは永久磁石により分離することができる。
【発明を実施するための最良の形態】
【００１８】
以下の非限定的な実施例を参照して本発明を詳細に説明する。
【００１９】
実施例１．
デキストラン（ＭＷ＝４０，０００Ｄ，Ｆｌｕｋａ）３６ｇを水１２０ｍｌに溶解した。２．５％（ｗ／ｗ）水性マグネタイトサスペンジョン（ミクロモード，４５−００−２０２，粒子径：２００ｎｍ）１８０ｍｌを４０℃に加熱し、マイクロフルイダイザＭ−１１０Ｙにおいて５００ｂａｒで１０ｍｉｎ超均質化させた。圧力を１０００ｂａｒに上昇した後、４０℃に加熱したデキストラン溶液を超均質化したマグネタイトサスペンジョンに加えた。デキストラン・マグネタイト・サスペンジョンを１０００ｂａｒおよび９０℃において２０ｍｉｎ超均質化させた。室温に冷却後、過剰のデキストランを分離するため、得られた磁性ナノ粒子を永久磁石で１５ｍｉｎ分離し、水４０ｍｌに再懸濁させた。得られた磁性ナノ粒子の流体力学的直径（hydrodynamische Durchmesser）は、１３０〜１４０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｉｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、５８〜６２％（ｗ／ｗ）である。
【００２０】
実施例２．
実施例１と同様に、粒子合成を実施した。この場合、全超均質化中の圧力は、５００
ｂａｒであった。生ずる磁性ナノ粒子の流体力学的径は、１６０〜１８０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｉｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、５８〜６２％（ｗ／ｗ）である。
【００２１】
実施例３．
粒子分析は、実施例１と同様に行った。この場合、デキストランとマグネタイトとの間の重量比８：１（実施例１）は、１２：１に増大した。更に、デキストラン（ＭＷ＝４０，０００Ｄ，Ｆｌｕｋａ）５４ｇを水１８０ｍｌに溶解した。生ずる磁性ナノ粒子の流体力学的径は、１３０〜１４０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｌｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、５２〜５６％（ｗ／ｗ）である。
【００２２】
実施例４．
エチレンイミン・ポリマー溶液（５０％（ｖ／ｖ），ＭＷ＝６００〜１，０００ｋＤ，Ｆｌｕｋａ）１２ｇを水３０ｍｌと混合した。２．５％（ｗ／ｗ）水性マグネタイトサスペンジョン（ミクロモード，４５−００−２０２，粒子径：２００ｎｍ）６０ｍｌを４０℃に加熱し、マイクロフルイダイザＭ−１１０Ｙにおいて５００ｂａｒで１０ｍｉｎ超均質化させた。圧力を１０００ｂａｒに上昇した後、４０℃に加熱したエチレンイミン・ポリマー溶液を超均質化したマグネタイトサスペンジョンに加えた。エチレンイミン・マグネタイト・サスペンジョンを１０００ｂａｒおよび９０℃において２０ｍｉｎ超均質化（ultrahomogenisiert）させた。室温に冷却後、過剰のポリマーを分離するため、得られた磁性ナノ粒子を永久磁石で１５ｍｉｎ分離し、水２５ｍｌに再懸濁させた。得られた磁性ナノ粒子の流体力学的径は、８０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｉｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、６０〜６５％（ｗ／ｗ）である。
【００２３】
実施例５．
デキストラン（ＭＷ＝４０，０００Ｄ，Ｆｌｕｋａ）７２ｇを水１８０ｍｌに溶解した。１．５％（ｗ／ｗ）水性マグヘマイトサスペンジョン（Ｈｏｌｍｅｓ ｅｔ ａｌ．，Ｊ．Ｍａｇｎ．Ｍａｇｎ．Ｍａｔｅｒ．１２２，１３４（１９９３）にもとづき調製，粒子径：２０ｎｍ，ｐＨ＝１．６〜２．０）９０ｍｌを４０℃に加熱し、マイクロフルイダイザＭ−１１０Ｙにおいて５００ｂａｒで５ｍｉｎ超均質化させた。４０℃に加熱したデキストラン溶液を超均質化させたマグヘマイトサスペンジョンに添加した後、０．１Ｍ苛性ソーダ水溶液１２０ｍｌを添加してサスペンジョンを中和した。室温に冷却後、高勾配磁界を使用して、得られた磁性ナノ粒子を水洗した。得られた磁性ナノ粒子の流体力学的直径は、６０〜７０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｉｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、５０〜５２％（ｗ／ｗ）である。
【００２４】
実施例６．
エチレングリコール・スペーサーを介してカルボン酸末端基を官能化するため、実施例１の５％（ｗ／ｗ）デキストラン・マグネタイト・ナノ粒子サスペンジョン（粒子径：１３０〜１４０ｎｍ）を０．５Ｍ２−モルホリノ（Morpholino-）エタンスルホン酸緩衝液（ｐＨ＝６．３）５ｍｌと混合した。Ｎ−エチル−Ｎ´−（３−ジメチルアミノプロピル）カルボジイミドヒドロクロライド１２０ｍｇおよび３，６−ジオキサオクタン二酸１２０ｍｇを、それぞれ、０．１Ｍ２−モルホリノエタンスルホン酸緩衝液（ｐＨ＝６．３）５ｍｌに溶解し、一緒にした。上記溶液を５０℃において１０ｍｉｎ培養した後、ナノ粒子サスペンジョンに添加を行った。粒子サスペンジョンを室温において２ｈ震盪した。永久磁石による分離後、ナノ粒子を水に再懸濁させた。粒子表面上のカルボン酸基の密度について、流動電位測定によって４０〜５０ｎｍｏｌ／ｍｇの数値が得られた（０．００１Ｎポリ(ジアリルジメチル塩化アンモニウム）溶液に対して高分子電解質滴定，Ｍｕｅｔｅｋ ＰＣＤ ０３ ｐＨ）。生じた磁性ナノ粒子の流体力学的直径は、１２０〜１３０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｉｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、６０〜６５％（ｗ／ｗ）である。
【００２５】
実施例７．
粒子表面上のストレプトアビジンの共有結合のため、粒子表面にカルボン酸末端基を有する実施例６の２％（ｗ／ｗ）デキストラン・マグネタイト・ナノ粒子サスペンジョン１０ｍｌを０．５Ｍ２−モルホリノ−エタンスルホン酸緩衝液（ｐＨ＝６．３）２．５ｍｌと混合した。Ｎ−エチル−Ｎ´−（３−ジメチルアミノプロピル）カルボジイミドヒドロクロライド２０ｍｇおよびＮ−ヒドロキシスクシンイミド４０ｍｇを、それぞれ、０．１Ｍ２−モルホリノエタンスルホン酸緩衝液（ｐＨ＝６．３）１ｍｌに溶解し、ナノ粒子サスペンジョンに加えた。粒子サスペンジョンを室温において２ｈ震盪した。永久磁石による分離後、ナノ粒子を水に再懸濁させた。ストレプトアビジン（Ｍｏｌｅｃｕｌａｒ Ｐｒｏｂｅｓ）１ｍｇの添加後、粒子サスペンジョンを室温において３ｈ震盪した。反応箇所の飽和のため、０．４Ｍグリシン溶液２ｍｌの添加後、粒子サスペンジョンを室温において更に１ｈ震盪した。永久磁石による分離後、ナノ粒子を、１回、ＰＢＳ緩衝液（ｐＨ＝７．４）１０ｍｌで洗浄し、ＰＢＳ緩衝液（ｐＨ＝７．４）５ｍｌに再懸濁させた。デキストラン・マグネタイト・ナノ粒子上の共有結合されたストレプトアビジンの濃度は、１．５〜２μｇストレプトアビジン／ｍｇ粒子である。生じた磁性ナノ粒子の流体力学的直径は、１３０〜１４０ｎｍである（光子相関顕微鏡，Ｚｅｔａｓｉｚｅｒ ３０００，Ｍａｌｖｅｒｎ Ｉｎｓｔｒ．製）。粒子中の鉄成分は、６０〜６５％（ｗ／ｗ）である。
【産業上の利用可能性】
【００２７】
本発明にもとづき調製した磁性ナノ粒子は、各種の生命科学用途に使用できる。即ち、上記粒子は、バイオ分析分野、診断分野、バイオ分離プロセスにおける使用および大処理量スクリーニングにおける担体材料としての使用に特に好適である。更に、小さい径と優れたコロイド安定性との組合せによって、例えば、注入（注射）可能な造影剤、放射性同位体キャリヤまたは作用物質デポの形で、ビボ用途に使用できる。このような用途について、本発明に係る粒子を殺菌フィルタリングによって処理することができると云うことは特に有利である。
【図面の簡単な説明】
【００２８】
【図１】サスペンジョン中の粒子の磁気モーメントを示す図である。
【図２】サスペンジョンの、永久磁石を用いた粒子分離による吸光度変化を示す図である。

Claims (14)

  1. 金属酸化物およびポリマーから構成される磁性ナノ粒子において、該磁性ナノ粒子が５０重量％以上の金属を含み、２００ｎｍ未満の流体力学的径を有するものであって、
    ａ）５０Ｏｅ未満の磁界強度において、使用した金属酸化物よりも大きい磁化を示す特性を有し、
    ｂ）ＰＨ＞７を有する水性担持媒体中で、５００ｂａｒ以上の高圧均質化によって形成される、
    ことを特徴とする磁性ナノ粒子。
  2. 該磁性ナノ粒子が、水中および水溶液中において、外部磁界の作用なしで、長時間安定なコロイドを形成することを特徴とする請求項１の磁性ナノ粒子。
  3. 永久磁石によって、該磁性ナノ粒子が分離可能であることを特徴とする請求項１および２の１つに記載の磁性ナノ粒子。
  4. 金属酸化物が、鉄酸化物であることを特徴とする請求項１−３の１つに記載の磁性ナノ粒子。
  5. 鉄酸化物が、マグネタイトまたはマグヘマイトまたは対応する混合相であることを特徴とする請求項４に記載の磁性ナノ粒子。
  6. 金属酸化物が鉄酸化物を含み、鉄酸化物が、他の２価または３価の金属イオンの成分を含むことを特徴とする請求項１−５の１つに記載の磁性ナノ粒子。
  7. ポリマーが、合成ポリマーであることを特徴とする請求項１−６の１つに記載の磁性ナノ粒子。
  8. ポリマーが、天然のまたは誘導された多糖類であることを特徴とする請求項１−６の１つに記載の磁性ナノ粒子。
  9. 多糖類が、デキストランであることを特徴とする請求項８に記載の磁性ナノ粒子。
  10. デキストランが、官能基または生化学的に重要な基礎構造体（Substrukturen）によって誘導されたものであることを特徴とする請求項９に記載の磁性ナノ粒子。
  11. 請求項１−１０の１つに記載の磁性ナノ粒子の製造法において、水性担持媒体中で、５００ｂａｒ以上の圧力において、成分であるポリマーおよび金属酸化物を超均質化することを特徴とする磁性ナノ粒子製造法。
  12. 請求項１−１０の１つに記載の磁性ナノ粒子の製造法において、成分である金属酸化物を、対応する金属塩または金属水酸化物からその状態において（in situ）形成することを特徴とする磁性ナノ粒子製造法。
  13. 担持媒体が、アンモニア水溶液であることを特徴とする請求項１−１２の１つに記載の磁性ナノ粒子製造法。
  14. 金属酸化物およびポリマーから構成され、５０重量％以上の金属を含み、２００ｎｍ未満の流体力学的径を有する、磁性ナノ粒子の製造方法であって、
    ＰＨ＞７を有する水性担持媒体中で、５００ｂａｒ以上の高圧で均質化を行う工程を含む、ことを特徴とする磁性ナノ粒子の製造方法。
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