JP2005531647A - 新規なイメージングプローブ - Google Patents
新規なイメージングプローブ Download PDFInfo
- Publication number
- JP2005531647A JP2005531647A JP2003583488A JP2003583488A JP2005531647A JP 2005531647 A JP2005531647 A JP 2005531647A JP 2003583488 A JP2003583488 A JP 2003583488A JP 2003583488 A JP2003583488 A JP 2003583488A JP 2005531647 A JP2005531647 A JP 2005531647A
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- JP
- Japan
- Prior art keywords
- alginate
- formula
- paramagnetic
- iii
- fluorinated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000003384 imaging method Methods 0.000 title abstract description 18
- 230000005298 paramagnetic effect Effects 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 38
- 235000010443 alginic acid Nutrition 0.000 claims description 111
- 229920000615 alginic acid Polymers 0.000 claims description 111
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 96
- 229940072056 alginate Drugs 0.000 claims description 94
- -1 Heptafluorobutyryl alginic acid Chemical class 0.000 claims description 69
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical group CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 55
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 24
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 229920000642 polymer Polymers 0.000 claims description 22
- 239000011737 fluorine Substances 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 19
- 108090000623 proteins and genes Proteins 0.000 claims description 19
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- 239000011324 bead Substances 0.000 claims description 17
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 claims description 16
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- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 12
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- HFKIAPZSCAKSNP-UHFFFAOYSA-N methyl 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,14,14,15,15,16,16,16-hentriacontafluorohexadecanoate Chemical compound COC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F HFKIAPZSCAKSNP-UHFFFAOYSA-N 0.000 claims description 5
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Abstract
Description
本発明は新規なイメージングプローブおよび前記プローブを診断のイメージングプロセスおよび生理的な機能を決定する他のイメージングプロセスに使用する方法に関する。さらに本発明は、本発明にかかるイメージングプローブによりカプセル化されたインプラントに関する。
糖尿病は巨大な比率の壊滅的な自己免疫性疾患である。それはグルコ−スの代謝不全によって特徴づけられ、とりわけ糖尿病患者の血液グルコ−スレベルの上昇に至る(高血糖症)。タイプ1の糖尿病は膵臓のランゲルハンス島内のインシュリン分泌ベータ細胞の自己免疫破壊により引き起こされる。糖尿病はタイプ1、すなわち、患者のβ−細胞が膵腺においてインシュリンを産生するのをやめる場合に発生するインシュリン依存性糖尿病(IDDM)と、タイプ2、すなわち、インシュリン代謝の弱った患者およびβ−細胞の機能不全の患者に起こるインシュリン非依存性糖尿病(NIDDM)に分類される。NIDDMは通常進行するのに数10年かかり、順次高インシュリン血症、トリグリセリド濃度の上昇、高濃度血液グルコ−スおよび最後に末期のβ−細胞の機能麻痺へとすすみ、この段階ではインシュリンレベルは急激に低下し、通常患者へのインシュリン投与が必要となる。IDDMの患者においては、β−細胞はリンパ球の浸透を含む自己免疫のプロセスによって選択的に破壊される。NIDDMの初期の段階においては、インシュリンをもっと多くとの需要に応えるべくβ−細胞の量は増加する。それからNIDDMが進行するのにつれてβ−細胞の量の減少が起こる可能性がある。β−細胞は、血液中のグルコース濃度の変化に応答してインシュリンを高度に調整された態様で分泌し、生理学的レベル内で刻々と調整するために応答する。インシュリンの不足は長期間の深刻な合併症を伴う長期間の高血糖をもたらす。たとえばインシュリン注射のような現在の処置は血液中のグルコース濃度の厳密な管理を提供せず、糖尿病の長期間の合併症を軽くしない。むき出しの、またはカプセル化された膵島の移植が、より良好な生理学的血中グルコース濃度の調整を提供するための異なる方法として探索されている。膵島移植は正常血糖の回復と糖尿病の長期間の合併症を軽減する見込みがある。膵島移植の広い適用は人体の膵臓の限定された供給のために妨げられ、適当なインシュリン分泌組織の利用可能性の向上と、安全性と生体内効率を確実にする確固とした品質評価方法の大幅な改善が必要とされる。
本発明はフッ素化および/または常磁性のポリウロニド(式I−IV)およびフッ素化および/または常磁性のタンパク質であって、イメージングプローブ、診断用薬およびコントラスト剤として有用なものに関する。
さらに、本発明は、式I−IVの本発明の化合物、および本明細書に記述されたフッ素化されたかまたは常磁性のタンパク質を使用するイメージング方法に関する。
式Iにおいては:
R1はOH、OX、Xを表し、R2はOH、OX、X、NHCOXを表し、R3はOH、OY、OX、NHX、アルキル、アルコキシアルキルを表し、R4はC=O、CH2、CNX、CF2を表し、好ましくはR1はOHまたはOXであり、R2はOHまたはOXであり、R1とR2の1つはOHであり、他方はOXであることが特に好ましい。
式IIにおいては:
R1はOH、OX、X、OR4を表し、R2はOH、OX、X、OR4を表し、R3はOH、Y、X、R4を表し、R4はアシル、アルキルまたはアリールを表し、好ましくはR1はOHまたはOXであり、R2はOHまたはOXであり、R3はOHであり、R4はC=Oであり、R1とR2の1つはOHであり、他方はOXであることが特に好ましい。
式IIIにおいては:
R1はOH、OX、Xを表し、R2はOH、OX、Xを表し、R3はH、N(X)3を表し、好ましくはR1はOHであり、R2はOHであり、R3はHまたはN(X)3である
式IVにおいては:
R1はOH、OX、Xを表し、R2はOH、OX、X、−OA(X)O−またはOA(R3)O−を表し、R3はアルキル、アシルを表し、
本発明を実施するに当たり、レセプターと結合したポリウロニドまたはタンパク質をフッ素含有部位および/または常磁性イオンで改質し、イメージングプローブ、診断薬、およびコントラスト剤としてMRIイメージングプロセスにおいて有用なものを生成する。
他の実施態様においては、常磁性化合物は、食道、胃、小腸および大腸を含む胃腸管内に、経口で、挿管により、または注腸により、蒸留水または任意の適当な医薬用ビヒクルのような適切な媒体中の分散質として投与される。該粒子は、好適には路、特に小腸の細胞に吸収され、静脈投与された粒子のように、器官または組織のT2に影響する。この方法では、ガン、および潰瘍のような消化器系の他の衰弱性疾病の診断および病変部位の特定が可能である。
カルボハイドレート、ポリマー、タンパク質骨格または基体を含む本発明の新規なフッ素化化合物は、それぞれの出発物質(骨格または基体部位)をフッ素部位で、以下に記載されるような通常のフッ素化学手法により処理することにより得られる。
アルギン酸、アルギン酸ナトリウム、高Gアルギネート、プロピレングリコールアルギネート、3,5,5’−トリス(トリフルオロメチル)オクタフルオロヘキサン酸、3,5,5’−トリス(トリフルオロエチル)オクタフルオロヘキサン酸、3,5,5’−トリス(トリフルオロメチル)オクタフルオロヘキサノール、パーフルオロ−3,6,9−トリオキサトリデカン酸メチルエステル、メチルパーフルオロヘキサデカノエート、デキストリン、ポリ(エチレングリコール)、および超常磁性酸化鉄ナノ粒子(3nm)はカルボマー社(マサチューセッツ州ウエストボロおよびカルフォルニア州、サンディエゴ)から入手した。アルギン酸、アルギン酸ナトリウム、高Gアルギネート、プロピレングリコールアルギネート出発物質は、それぞれ〜600,000、〜500,000、〜450,000および〜700,000ダルトンの分子量を有していた。ヘキサフルオロプロパンオキサイドおよびヘプタフルオロブチリルクロライドは、ランカスターシンセシス社(ニューハンプシャー州、ウンイドハム)から入手した。デオキソフルオル[ビス(2−メトキシエチル)アミノサルファー トリオキサイド]は、エアープロダクト社(ペンシルバニア州、アレンタウン)から入手した。ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ビスジフルオロ酢酸、酢酸ガドリニウム(III)、ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ビス(メチルカルボキシレート)、ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ジイソシアネート、およびアネキシンVはアルドリッチ社(ミズーリ州、セントルイス)から入手した。
DMSO中のヘプタフルオロブチリルクロライド(0.6当量)の溶液をアルギン酸に加え、雰囲気温度で6時間撹拌した。生成物をアセトンで沈殿させ、濾過し、アセトンで洗浄し、透折し、乾燥し、F9.07%のヘプタフルオロブチリルアルギン酸を得た。
ヘプタフルオロブチリルアルギネート(実施例1)の生体適合性結果が人体細胞培養物中で試験され、濃度0.2−1.0%において無毒性であることが見いだされた。
塩化メチレン中の3−[2−(パーフルオロヘキシル)−2−エトキシ]−1,2−エポキシプロパン(0.6当量)の溶液をアルギン酸に加え、雰囲気温度で6時間撹拌した。サスペンジョンを濾過し、塩化メチレンおよびアセトンで洗浄し、透折し、乾燥し、F20.41%の3−[2−(パーフルオロヘキシル)−2−ヒドロキシ]アルギネートを得た。
水中のパーフルオロトリ−n−ブチルアミン(1.1当量)の溶液をアルギン酸に加え、雰囲気温度で6時間撹拌した。生成物をアセトンで沈殿させ、濾過し、アセトンで洗浄し、透折し、乾燥し、F9.41%のパーフルオロトリ−n−ブチルアミンアルギネートを得た。
メタノール中のプロピレングリコールアルギネート溶液を、ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ビス(メチルカルボキシレート)、(Mw〜2,000ダルトン、0.6当量)で処理し、得られた粘稠なペーストを雰囲気温度で6時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F27.66%のパーフルオロポリマーでラベルしたアルギネートを得た。
DMSO中の6−[2−(パーフルオロヘキシル)−2−ヒドロキシ]アルギネート(実施例2、0.6当量)溶液を、乾燥アセトン中に溶解した5−N,N−ジメチルアミノ−1−ナフタレンスルホニル(DANSYL)クロライド(0.1当量)、および炭酸ナトリウム(0.1当量)で処理し、雰囲気温度で3時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、ダンシル化6−[2−(パーフルオロヘキシル)−2−ヒドロキシ]アルギネートを得た。
塩化メチレン中のヘキサフルオロプロピレンオキシド(0.8当量)の溶液を高グルロン酸含量(68%)のアルギン酸ナトリウムに加え、雰囲気温度で6時間撹拌した。サスペンジョンを濾過し、塩化メチレンおよびアセトンで洗浄し、透折し、乾燥し、F12.50%の3−[(ヘキサフルオロプロピル)−2−ヒドロキシ]アルギネートを得た。
塩化メチレン中のパーフルオロフェニルヒドラジン(0.6当量)の溶液を高グルロン酸含量(68%)のアルギン酸ナトリウムの水性溶液に加え、雰囲気温度で6時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F10.35%のパーフルオロフェニルヒドラゾンアルギネートを得た。
高グルロン酸含量(68%)のアルギン酸ナトリウムの水性溶液を、ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ビスジフルオロ酢酸(Mw〜500ダルトン、0.6当量)で処理し、得られた粘稠なペーストを雰囲気温度で6時間撹拌した。一部をフルオレセインイソチオシアネート(0.1当量)で4時間処理した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F22.64%のパーフルオロポリマーおよびFITCでラベルしたアルギネートを得た。
メタノール中のプロピレングリコールアルギネート溶液を、ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ビスジフルオロ酢酸(Mw〜2,000ダルトン、0.6当量)で処理し、得られた粘稠なペーストを雰囲気温度で6時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F33.04%のパーフルオロポリマーでラベルしたアルギネートを得た。
塩化メチレン中のパーフルオロアニリン(0.6当量)の溶液を高グルロン酸含量(68%)のアルギン酸ナトリウムの水性溶液に加え、雰囲気温度で6時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F19.35%のパーフルオロペンズアミドアルギネートを得た。
塩化メチレン中のパーフルオロアニリン(0.6当量)の溶液を高グルロン酸含量(68%)のアルギン酸ナトリウムの水性溶液に加えた。シアノボロヒドリドナトリウム(8.6当量)を加え、雰囲気温度で6時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F22.65%のパーフルオロアニリンアルギネートを得た。
塩化メチレン中のヘキサフルオロプロピレンオキシド(0.7当量)の溶液をプロピレングリコールアルギネートに加え、雰囲気温度で6時間撹拌した。サスペンジョンを濾過し、塩化メチレンおよびアセトンで洗浄し、透折し、乾燥し、F20.41%の3−[(ヘキサフルオロプロピル)−2−ヒドロキシ]プロピレングリコールアルギネートを得た。
メタノール中のプロピレングリコールアルギネートの溶液を、ポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α,ω−ジイソシアネート(Mw〜3,000、0.6当量)で処理し、得られた粘稠なペーストを雰囲気温度で6時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで洗浄し、濾過し、透折し、乾燥し、F29.99%のパーフルオロポリマーでラベルしたアルギネートを得た。
高グルロン酸含量(68%)のアルギネートの水性溶液を、パーフルオロ−3,6,9−トリオキサトリデカン酸メチルエステル(1.6当量)で処理し、得られた粘稠なペーストを雰囲気温度で16時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで2回洗浄し、濾過し、透折し、乾燥し、F30.25%のパーフルオロ−3,6,9−トリオキサトリデカノエートアルギネートを得た。
高グルロン酸含量(68%)のアルギネートのアセトン中の分散液を、1,3−ジイソプロピルカルボジイミド(0.8当量)で1時間処理し、ついで3,5,5’−トリス(トリフルオロメチル)オクタフルオロヘキサノール(0.6当量)で処理し、得られた粘稠なペーストを雰囲気温度で16時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで2回洗浄し、濾過し、透折し、乾燥し、F24.73%のパーフルオロ−3,5,5’−トリメチルヘキサノエートアルギネートを得た。
メタノール中のプロピレングリコールアルギネート溶液を、3,5,5’−トリス(トリフルオロメチル)オクタフルオロヘキサン酸(0.4当量)で処理し、得られた粘稠なペーストを雰囲気温度で16時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで2回洗浄し、濾過し、透折し、乾燥し、F14.71%のパーフルオロ3,5,5’−トリメチルヘキサノエートでラベルしたアルギネートを得た。
高グルロン酸含量(68%)のアルギネートの水性溶液を、メチルパーフルオロヘキサデカノエート(0.4当量)で処理し、得られた粘稠なペーストを雰囲気温度で16時間撹拌した。反応混合物をアセトンで沈殿させ、アセトンで2回洗浄し、濾過し、透折し、乾燥し、F32.36%のメチルパーフルオロヘキサデカノエートアルギネートを得た。
速く撹拌された酢酸ガドリニウム(III)の水性溶液(1.1当量)に、高グルロン酸含量(68%)のアルギン酸ナトリウムの希釈水性溶液をシリンジから滴下した。得られたゲルビーズを遠心分離し、上澄みを捨て、希釈塩化カルシウム溶液でのビーズの洗浄と遠心分離を2回行い、過剰のガドリニウムを除去した。磁化曲線はアルギネートビーズが常磁性であることを示した。0.22ミクロンのフィルターを通して成分溶液を濾過減菌し、一緒にすることにより減菌調製物を得た。常磁性ガドリニウムアルギネートビーズ(実施例18)が無毒性であることが細胞培養物中で見いだされた。
速く撹拌された超常磁性酸化鉄ナノ粒子(3nm、1.1当量)の、ポリ(エチレングリコール)(NFグレード、Mw 400、25%)を含む塩化カルシウム水性溶液10mmol中のサスペンジョンに、高グルロン酸含量(68%)のアルギン酸ナトリウムの希釈水性溶液をシリンジから滴下した。得られたゲルビーズを遠心分離し、上澄みを捨て、希釈塩化カルシウム溶液でのビーズの洗浄と遠心分離を2回行った。磁化曲線はアルギネートビーズが超常磁性であることを示した。0.22ミクロンのフィルターを通して成分溶液およびサスペンジョンを濾過減菌し、一緒にすることにより減菌調製物を得た。
速く撹拌された塩化カルシウム水性溶液10mmolに、高グルロン酸含量(68%)のアルギン酸ナトリウムの希釈水性溶液中の超常磁性酸化鉄ナノ粒子(3nm)のサスペンジョンをシリンジから滴下した。得られた被覆されたナノ粒子を遠心分離し、上澄みを捨て、希釈塩化カルシウム溶液でのナノ粒子の洗浄と遠心分離を2回行った。
速く撹拌された高グルロン酸含量(68%)のアルギン酸ナトリウムの希釈水性溶液に、ポリ(エチレングリコール)(NFグレード、Mw 400、25%)中の超常磁性酸化鉄ナノ粒子(3nm)のサスペンジョンをゆっくりと加えた。得られたサスペンジョンを10分間撹拌し、ついで70℃で30分加熱し、遠心分離した。上澄みを捨て、被覆されたナノ粒子を透析した。
速く撹拌された希釈水性デキストラン(Mw 10,000)に、ポリ(エチレングリコール)(NFグレード、Mw 400、25%)中の超常磁性酸化鉄ナノ粒子(3nm)のサスペンジョンをゆっくりと加えた。得られたサスペンジョンを10分間撹拌し、ついで70℃で30分加熱し、遠心分離した。上澄みを捨て、被覆されたナノ粒子を透析した。
速く撹拌された、実施例22からの超常磁性酸化鉄デキストラン被覆ナノ粒子の水性溶液に、パラ過ヨウ素酸ナトリウム(0.05当量)を加え、得られた混合物を1時間撹拌した。エチレングリコールを加え、混合物を遠心分離した。上澄みを捨て、PBS緩衝液での酸化された被覆ナノ粒子の洗浄と遠心分離を2回行った。酸化された被覆ナノ粒子をアネキシンVの緩衝液に加えた。得られた混合物を4℃で25分間撹拌し、ついで遠心分離した。上澄みを捨て、所望の結合体を得た。
実施例23の手順に従って、実施例20または21で調製されたアルギネートで被覆されたナノ粒子を使用して、酸化工程を行うか、または直接に、所望の結合体を得た。
実施例22および23の手順に従って、フルオレセインイソシアネートでラベルされたアネキシンVを、ラベルされていないタンパク質の代わりに使用し、被覆された超常磁性体酸化鉄ナノ粒子との所望の蛍光性結合体を得た。別法として、蛍光性アルギネート(たとえば実施例5および8)が使用できる。
DMSO中のヘプタフルオロブチリルクロライド(0.6当量)の溶液をヒドロキシエチルスターチに加え、雰囲気温度で12時間撹拌した。生成物をアセトンで沈殿させ、濾過し、アセトンで洗浄し、透折し、乾燥し、F16.75%のヘプタフルオロブチリルヒドロキシエチルスターチを得た。
アルギン酸の酸性水性分散液をパーフルオロトリ−n−ブチルアミン(1.6当量)で、雰囲気温度で12時間処理した。生成物をアセトンで沈殿させ、濾過し、アセトンで洗浄し、透折し、乾燥し、F11.50%のパーフルオロトリ−n−ブチルアミンアルギネートを得た。
参考文献
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Claims (17)
- 式I、II、IIIまたはIVのポリマーを含むフッ素化または常磁性ポリウロニドポリマー;
ここで、
式Iにおいては:
R1はOH、OX、Xを表し、R2はOH、OX、Xを表し、R3はOH、OY、OX、NHX、アルキル、アルコキシアルキルを表し、R4はC=O、CH2、CNX、CF2を表し、
式IIにおいては:
R1はOH、OX、X、OR4を表し、R2はOH、OX、X、OR4を表し、R3はOH、Y、Xを表し、R4はアシル、アルキルまたはアリールを表し、
式IIIにおいては:
R1はOH、OX、Xを表し、R2はOH、OX、Xを表し、R3はH、N(X)3を表し、
式IVにおいては:
R1はOH、OX、Xを表し、R2はOH、OX、X、−OA(X)O−またはOA(R5)O−を表し、R5はアルキル、アシルを表し、Aは非常磁性イオンを表す、
Mは遷移金属又はランタニド列の任意の常磁性イオンを表し、aは任意の数であり、bは1/aである、
式I−IVのすべてについて、
Xはフッ素含有部位、ルミネセント残基、蛍光性残基、フッ素化したルミネセント残基、あるいはフッ素化した蛍光性残基であり、
YはCH2C(OH)CH3であり、
m、p、x、y、zは1〜150であり、nは10から10000(両端の値を含む)である。 - 以下のものからなる群から選択される化合物を含む、請求項1記載のポリウロニドポリマー;
a.以下の式のヘプタフルオロブチリルアルギン酸;
b.以下の式の6−[3−[2−(パーフルオロヘキシル)−2−エトキシ]−2−ヒドロキシプロピル]アルギン酸;
c.以下の式のパーフルオロトリ−n−ブチルアミンアルギネート;
d.以下の式のポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α−メチル−カルボキシレート−ω−カルボキシレート−プロピレングリコールアルギネート;
e.以下の式の6−[2−(パーフルオロヘキシル)−2−ヒドロキシ]DANSYLアルギン酸;
f.以下の式の3−[(ヘキサフルオロプロピル)−2−ヒドロキシ]アルギン酸;
g.以下の式のパーフルオロフェニルヒドラゾンアルギン酸;
h.以下の式のポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α−ジフルオロ酢酸−ω−ジフルオロアセチルフルオレセインアルギネート;
i.以下の式のポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α−ジフルオロ酢酸−ω−ジフルオロアセチルプロピレングリコールアルギネート;
j.以下の式のパーフルオロベンズアミドアルギネート;
k.以下の式のパーフルオロアニリンアルギネート;
l.以下の式の3−[(ヘキサフルオロプロピル)−2−ヒドロキシ]プロピレングリコールアルギネート;
m.以下の式のポリテトラフルオロエチレンオキシド−コ−ジフルオロメチレンオキシド−α−トリルウレタン−ω−トリルイソシアネートプロピレングリコールアルギネート;
n.以下の式のパーフルオロ−3,6,9−トリオキサトリデカノエートアルギネート;
o.以下の式の3,5,5’−トリス(トリフルオロメチル)オクタフルオロヘキサノエートアルギネート;
p.以下の式の3,5,5’−トリス(トリフルオロメチル)オクタフルオロヘキサノエートプロピレングリコールアルギネート;
q.以下の式のメチルパーフルオロヘキサデカノエートアルギネート;
r.ヘプタフルオロブチリルヒドロキシエチルスターチ、および
s.パーフルオロトリ−n−ブチルアミンアルギネート。 - Mがガドリニウム(III)、鉄(III)、マンガン(IIおよびIII)、クロム(III)、銅(II)、ジスプロシウム(III)、テルビウム(III)、ホルミウム(III)、エルビウム(III)、およびユウロピウム(III)からなる群から選択される請求項1記載のフッ素化および/または常磁性ポリマー。
- a.式IにおいてR1がOHまたはOXであり、R2がOHまたはOXであり、R3がOHであり、R4がC=Oであり;
b.式IIにおいてR1がOHまたはOXであり、R2がOHまたはOXであり、R3がOHであり、R4がC=Oであり;
c.式IIIにおいてR1がOHであり、R2がOHであり、R3がH、N(X)3であり、
d.式IVにおいてR1がOHまたは−OA(X)O−であり、R2がOHまたは−OA(X)O−であり、Mがガドリニウム(III)、鉄(III)、マンガン(II)、またはジスプロシウム(III)である、請求項1記載のフッ素化および/または常磁性ポリマー。 - Xがフルオロアルキル、フルオロアリ−ル、フルオロアシル、パ−フルオロアルキル、パ−フルオロアリ−ル、パ−フルオロアシル、パ−フルオロポリマー、フルオロアミン、フルオロカルバメート、フルオロトリアジン、フルオロスルホニルアルキル誘導体、F、CF3、COCxFy、CF3CO2、CxFyHz、([CH2]mO)x(CH2CF2O)y(CF2CF2O)z(CF2)2CF2CH2O(CH2)pOH、CH2C(OH)CxFyHz、CxFyHzOp、COCxFyHz、OCH2CxFz[CxFzO]mF、CH2C(CH3)CO2CxHz(CF2)mCF3、CH2(CF2O)x(CF2CF2O)y(CF2O)zCF2CH2OH、NHCxFyHzOp、CH2CF2O[CF2CF2O]mCF2OCF2CH2OH、COCxHz(CF2)mCF3、CO−CF2O[CF2CF2O]nCF2OCF2CO2H、CO−CF(CF3)[CF(CF3)CF2O]mF([CH2]mO)x(CH2CF2O)y(CF2CF2O)zCF2CH2O(CH2)pOH、SO2[CF2]xCF3、CF3SO3、N[CxFyHz]p、CxHzCO2CxHz(CF2)mCF3、またはCOCxFy[CpFzO]mFであり、YはCH2C(OH)CH3であり、m、p、x、y、zは1〜150であり、nは10から10000(両端の値を含む)である、請求項1記載のフッ素化および/または常磁性ポリマー。
- 常磁性ガドリニウムアルギネートビーズまたは常磁性酸化鉄アルギネートビーズを含む、常磁性アルギネートビーズ。
- 常磁性酸化鉄アルギネートでコーティングされた粒子、または常磁性酸化鉄デキストランでコーティングされた粒子を含む、常磁性粒子。
- 遷移金属またはランタニド列の常磁性イオンと結合され、または錯体とされた生物活性タンパク質を含む、生物活性タンパク質常磁性結合体。
- 常磁性タンパク質結合体が、酸化鉄アネキシン結合体、超常磁性酸化鉄アネキシン結合体または蛍光性超常磁性酸化鉄アネキシン結合体である、請求項8記載の生物活性タンパク質常磁性結合体。
- ポリウロニドがアルギネートであり、該アルギネートが少なくとも50重量%のα−L−グルロン酸含有量を有する、請求項1記載のフッ素化ポリウロニドポリマー。
- a.所望の生物活性化合物を生成する生細胞、
b.1以上の請求項1記載のポリマーを含み、
該ポリマーが該生細胞をカプセル化し、被移植体のインプラントへの免疫反応を防止し、MRI検査法によるインプラントの評価を許容する、哺乳類の被移植体のためのインプラント。 - ポリマーがフッ素化または常磁性アルギネートである、請求項11記載のインプラント。
- 細胞がインシュリン生成性の人類またはブタの膵臓B膵島細胞である、請求項11記載のインプラント。
- ポリマーがフッ素化または常磁性アルギネートである、請求項11記載のインプラント。
- a.請求項1記載の1以上のフッ化および/または常磁性ポリマーを有効量患者に投与し、
b.患者を、投与されたポリマーの蓄積が予測される組織/器官のMRIにかけ、
c.得られたMRI画像から前記組織/器官を評価する、
ことを含む、磁気共鳴画像法(MRI)の有効性を改良する方法。 - ポリマーがフッ素化ポリウロニドである、請求項15記載の方法。
- ポリマーが常磁性ポリウロニドである、請求項15記載の方法。
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JP2005531648A (ja) * | 2002-04-11 | 2005-10-20 | カルボマー インク | 生体適合性物質およびプローブ類 |
JP2010506862A (ja) * | 2006-10-18 | 2010-03-04 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | 過弗素化されたpeg基を有する金属キレート類、それらの製剤方法、及びそれらの使用 |
JP2014224258A (ja) * | 2013-05-14 | 2014-12-04 | 合浦企業有限公司Hopewangent Co.,Ltd | 金属結晶含有のアルギン酸モノマー、金属結晶含有のアルギン酸塩モノマー及び金属結晶含有のアルギン酸塩ヒドロゲル及びその製造方法 |
JP2019512563A (ja) * | 2016-03-22 | 2019-05-16 | オーボ アカデミー ユニヴァーシティー | 蛍光増白剤としての多糖誘導体 |
WO2023149402A1 (ja) * | 2022-02-03 | 2023-08-10 | 東ソー株式会社 | 水溶性キレートポリマー及びその製造方法 |
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