JPH10513445A - 延長された血液保持を有する診断画像造影剤 - Google Patents
延長された血液保持を有する診断画像造影剤Info
- Publication number
- JPH10513445A JPH10513445A JP8523543A JP52354396A JPH10513445A JP H10513445 A JPH10513445 A JP H10513445A JP 8523543 A JP8523543 A JP 8523543A JP 52354396 A JP52354396 A JP 52354396A JP H10513445 A JPH10513445 A JP H10513445A
- Authority
- JP
- Japan
- Prior art keywords
- contrast agent
- ppbm
- plasma
- moiety
- bhem
- 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.)
- Granted
Links
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- ZSDLYSDDELEVDD-UFTMZEDQSA-K 2-[[(2r)-2-[bis(carboxylatomethyl)amino]-3-[(4,4-diphenylcyclohexyl)oxy-oxidophosphoryl]oxypropyl]-[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;gadolinium(3+);hydron Chemical compound [H+].[H+].[H+].[Gd+3].C1CC(OP([O-])(=O)OC[C@@H](CN(CCN(CC([O-])=O)CC([O-])=O)CC(=O)[O-])N(CC([O-])=O)CC([O-])=O)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 ZSDLYSDDELEVDD-UFTMZEDQSA-K 0.000 description 9
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- 239000000546 pharmaceutical excipient Substances 0.000 description 1
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 1
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- 238000006366 phosphorylation reaction Methods 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
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- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- PNYPSKHTTCTAMD-UHFFFAOYSA-K trichlorogadolinium;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Gd+3] PNYPSKHTTCTAMD-UHFFFAOYSA-K 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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- A61K49/103—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being acyclic, e.g. DTPA
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- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
- A61B6/50—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment specially adapted for specific body parts; specially adapted for specific clinical applications
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.a)画像増強部分(IEM); b)血漿タンパク質結合部分(PPBM);および c)血液半減期延長部分(BHEM)、 を含有する診断画像化のための造影剤であって、 血漿タンパク質に対して少なくとも約10%結合、およびラット血漿薬物動力学実 験において、BHEMを有さずにIEMおよびPPBMのみの組合せについて観察されるも のより少なくとも約20%大きな血漿濃度対0〜10分の時間曲線下の領域を実証す る造影剤。 2.前記画像増強部分が有機分子、金属イオン、塩またはキレート、粒子、鉄粒 子、あるいは標識されたペプチド、タンパク質、ポリマーまたはリポソームから なる群より選択される、請求項1に記載の造影剤。 3.前記画像増強部分が生理学的に適合し得る、鉄粒子、あるいは原子番号21〜 29、42、44、または57〜83を有する1つ以上の常磁性金属イオンに錯体化した1 つ以上の環状または非環状有機キレート剤からなる金属キレート化合物である、 請求項1に記載の造影剤。 4.前記画像増強部分がヨウ素化有機分子、あるいは原子番号57〜83を有する1 つ以上の金属イオンに錯体化した1つ以上の環状または非環状有機キレート剤か らなる生理学的に適合し得る金属キレート化合物である、請求項1に記載の造影 剤。 5.前記画像増強部分がガスで充填した泡または粒子、あるいは原子番号21〜29 、42、44または57〜83を有する1つ以上の金属イオンに錯体化した1つ以上の環 状または非環状有機キレート剤からなる生理学的に適合し得る金属キレート化合 物である、請求項1に記載の造影剤。 6.前記画像増強部分が放射性分子からなる、請求項1に記載の造影剤。 7.前記画像増強部分が、原子番号27、29、31、43、47、49、75、79、82または 83を有する1つ以上の金属イオンに錯体化した1つ以上の環状または非環状有機 キレート剤からなる生理学的に適合し得る金属キレート化合物である、請求項1 に記載の造影剤。 8.前記画像増強部分が、Tc-99mに錯体化した1つ以上の環状または非環状有機 キレート剤からなる生理学的に適合し得る金属キレート化合物である、請求項1 に記載の造影剤。 9.前記画像増強部分が有機染料または無機染料である、請求項1に記載の造影 剤。 10.前記血漿タンパク質結合部分がヒト血清アルブミンに結合する、請求項1 に記載の造影剤。 11.前記血漿タンパク質結合部分が脂肪族基および/または少なくとも1つの アリール環を含有する、請求項10に記載の造影剤。 12.前記血漿タンパク質結合部分が、疎水性アミノ酸残基および/または疎水 性末端基または親水性末端基を含有または含有しない置換基を含むペプチドを含 有する、請求項10に記載の造影剤。 13.前記血漿タンパク質結合部分が少なくとも1つのアリール環を含有する、 請求項10に記載の造影剤。 14.前記血漿タンパク質結合部分が非平面様式において堅固に保持された少な くとも2つのアリール環を含有する、請求項10に記載の造影剤。 15.前記血液半減期延長部分が生理学的pHの水溶液中で1つ以上の完全または 部分的な負電荷を有し、ここで負電荷は画像増強部分への共有結合または配位共 有結合により部分的または完全に中和され得ない、請求項1に記載の造影剤。 16.前記造影剤が血漿タンパク質に対して少なくとも約50%の結合を実証する 、請求項1に記載の造影剤。 17.前記造影剤が血漿タンパク質に対して少なくとも約80%の結合を実証する 、請求項1に記載の造影剤。 18.前記造影剤が血漿タンパク質に対して少なくとも約95%の結合を実証する 、請求項1に記載の造影剤。 19.前記造影剤が、ラット血漿薬物動力学実験において、BHEM非存在下でIEM およびPPBMのみの組合せについて観察されるものより少なくとも約40%大きな血 漿濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、また は18に記載の造影剤。 20.前記造影剤が、ラット血漿薬物動力学実験において、BHEM非存在下でIEM およびPPBMのみの組合せについて観察されるものより少なくとも約70%大きな血 漿濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、また は18に記載の造影剤。 21.前記造影剤が、ラット血漿薬動力学実験において、BHEM非存在下でIEMお よびPPBMのみの組合せについて観察されるものより少なくとも約100%大きな血 漿濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、また は18に記載の造影剤。 22.前記造影剤が、ラット血漿薬動力学実験において、BHEM非存在下でIEMお よびPPBMのみの組合せについて観察されるものより約20%〜約100%大きな血漿 濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、または 18に記載の造影剤。 23.前記造影剤が、ラット血漿薬物動力学実験において、BHEM非存在下でIEM およびPPBMのみの組合せについて観察されるものより約40%〜約100%大きな血 漿濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、また は18に記載の造影剤。 24.前記造影剤が、ラット血漿薬動力学実験において、BHEM非存在下でIEMお よびPPBMのみの組合せについて観察されるものより約70%〜約100%大きな血漿 濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、または 18に記載の造影剤。 25.前記造影剤が、ラット血漿薬物動力学実験において、BHEM非存在下でIEM およびPPBMのみの組合せについて観察されるものより少なくとも約100%大きな 血漿濃度対0〜10分の時間曲線下の領域を実証する、請求項1、16、17、ま たは18に記載の造影剤。 26.前記造影剤を選択された生物学的成分に標的化させ得る標的化部分をさら に含有する、請求項1、16、17、または18に記載の造影剤。 27.前記標的化部分が親油性物質、レセプターリガンド、および抗体からなる 群より選択される、請求項26に記載の造影剤。 28.画像増強部分および血漿タンパク質結合部分を含有し、そして血漿タンパ ク質への少なくとも約10%の結合を実証する、診断画像造影剤の血液半減期を延 長するための方法であって、血漿への造影剤の結合を減少させないような、かつ 該薬剤がラット血漿薬物動力学実験において、血液半減期延長部分の非存在化で 該画像増強部分および該タンパク質血漿結合部分のみの組合せについて観察され るものより少なくとも約20%大きい、血漿濃度対0〜10分の時間曲線下の領域を 実証するような該薬剤内の部位に該血液半減期延長部分を該造影剤に組み込む工 程を包含する、方法。 29.前記血液半減期延長部分が、生理学的pHの水溶液中で1つ以上の完全また は部分的な負電荷を有し、ここで該負電荷または電荷は前記画像増強部分への共 有結合または配位共有結合により部分的または完全に中和され得ない、請求項2 8に記載の方法。 30.前記造影剤の前記血漿濃度対0〜10分の時間曲線下の前記領域が、前記血 液半減期延長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合 部分のみの組合せについて観察されるものより少なくとも約40%大きい、請求項 28に記載の方法。 31.前記造影剤の前記血漿濃度対0〜10分の時間曲線下の前記領域が、前記血 液半減期延長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合 部分のみの組合せについて観察されるものより少なくとも約70%大きい、請求項 28に記載の方法。 32.前記造影剤の前記血漿濃度対0〜10分の時間曲線下の前記領域が、前記血 液半減期延長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合 部分のみの組合せについて観察されるものより少なくとも約100%大きい、請求 項28に記載の方法。 33.前記造影剤の前記血漿濃度対時間曲線下の前記領域が、前記血液半減期延 長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合部分のみの 組合せについて観察されるものより約20%〜約100%大きい、請求項28に記載 の方法。 34.前記造影剤の前記血漿濃度対時間曲線下の前記領域が、前記血液半減期延 長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合部分のみの 組合せについて観察されるものより約40%〜約100%大きい、請求項28に記載 の方法。 35.前記造影剤の前記血漿濃度対時間曲線下の前記領域が、前記血液半減期延 長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合部分のみの 組合せについて観察されるものより約70%〜約100%大きい、請求項28に記載 の方法。 36.前記造影剤の前記血漿濃度対0〜10分の時間曲線下の前記領域が、前記血 液半減期延長部分の非存在化で前記画像増強部分および前記タンパク質血漿結合 部分のみの組合せについて観察されるものより少なくとも約100%大きい、請求 項28に記載の方法。 37.以下の式: ここで、IEMは画像増強部分であり、 Lはリンカー部分であり、 BHEMは、2つ以上の正電荷を帯びた水素原子、またはIEMに共有結合または 配位共有結合することにより部分的または完全に中和され得ない2つ以上の孤立 電子対を有する血液半減期延長部分であり、そしてスルホン、尿素、チオ尿素、 アミン、スルホンアミド、カルバメート、ペプチド、エステル、カルボネート、 アセタールおよび ここで、ZはP、W、MoまたはSであり、 Y1、Y2はOまたはSであり、 Y3、Y4は、O、Sであるか、または存在せず、 R2は、H、C1-6アルキルであるか、または存在せず、 PPBMは、少なくとも7個の炭素原子を含む血漿タンパク質結合部分であり、 mは、0〜4に等しくあり得、 s、oおよびpは、同じであっても異なってもよく、かつ1〜4に等しくあり得 、 そしてqは少なくとも1である、 を有する、診断用画像化造影剤。 38.前記BHEMが、 ここで、ZがP、W、MoまたはSであり、 Y1、Y2がOまたはSであり、 Y3、Y4が、O、Sであるか、または存在せず、 R2が、H、C1-6アルキルであるか、または存在しない、 請求項37に記載の造影剤。 39.前記BHEMが、ホスフェートまたはそのエステル形態である、請求項37に 記載の造影剤。 40.前記PPBMが少なくとも13個の炭素原子を含む、請求項37に記載の造影剤 。 41.前記PPBMが少なくとも18個の炭素原子を含む、請求項37に記載の造影剤 。 42.前記PPBMが少なくとも2.0のlogPの寄与を有する、請求項37に記載の造 影剤。 43.前記PPBMが少なくとも3.0のlogPの寄与を有する、請求項37に記載の造 影剤。 44.前記PPBMが少なくとも4.0のlogPの寄与を有する、請求項37に記載の造 影剤。 45.以下の式: ここで、IEMは画像増強部分であり、 BHEMは、2つ以上の正電荷を帯びた水素原子、またはIEMに共有結合または 配位共有結合することにより部分的または完全に中和され得ない2つ以上の孤立 電子対を有する血液半減期延長部分であり、そしてスルホン、尿素、チオ尿素、 アミン、スルホンアミド、カルバメート、ペプチド、エステル、カルボネート、 アセタールおよび ここで、ZはP、WまたはMoであり、 Y1、Y2はOまたはSであり、 Y3、Y4は、O、Sであるか、または存在せず、 R2は、H、C1-6アルキルであるか、または存在せず、 PPBMは、少なくとも7個の炭素原子を含む血漿タンパク質結合部分であり、 sおよびoは、同じであっても異なってもよく、かつ1〜4に等しくあり得、 そしてrは少なくとも1である、 を有する、診断用画像化造影剤。 46.前記BHEMが、 ここで、ZがP、WまたはMoであり、 Y1、Y2がOまたはSであり、 Y3、Y4が、O、Sであるか、または存在せず、 R2が、H、C1-6アルキルであるか、または存在しない、 請求項45に記載の造影剤。 47.前記BHEMが、ホスフェートまたはそのエステル形態である、請求項45に 記載の造影剤。 48.前記PPBMが少なくとも13個の炭素原子を含む、請求項45に記載の造影剤 。 49.前記PPBMが少なくとも18個の炭素原子を含む、請求項45に記載の造影剤 。 50.前記PPBMが少なくとも2.0のlogPの寄与を有する、請求項45に記載の造 影剤。 51.前記PPBMが少なくとも3.0のlogPの寄与を有する、請求項45に記載の造 影剤。 52.前記PPBMが少なくとも4.0のlogPの寄与を有する、請求項45に記載の造 影剤。 53.以下の式: ここで、IEMは画像増強部分であり、 Lは、リンカー部分であり、 BHEMは、2つ以上の正電荷を帯びた水素原子、またはIEMに共有結合または 配位共有結合することにより部分的または完全に中和され得ない2つ以上の孤立 電子対を有する血液半減期を延長する部分であり、そしてスルホン、尿素、チオ 尿素、アミン、スルホンアミド、カルバメート、ペプチド、エステル、カルボネ ート、アセタール、SO3 -またはエステル形態および ここで、ZはP、W、MoまたはSであり、 Y1、Y2はOまたはSであり、 Y3、Y4は、O、Sであるか、または存在せず、 R2は、H、C1-6アルキルであるか、または存在せず、 PPBMは、少なくとも7個の炭素原子を含む血漿タンパク質結合部分であり、 mは、0〜4に等しくあり得、 sおよびoは、同じであっても異なってもよく、かつ1〜4に等しくあり得る、 を有する、診断用画像化造影剤。 54.前記BHEMが、 ここで、ZがP、W、MoまたはSであり、 Y1、Y2がOまたはSであり、 Y3、Y4が、O、Sであるか、または存在せず、 R2が、H、C1-6アルキルであるか、または存在しない、 請求項53に記載の造影剤。 55.前記BHEMが、ホスフェートまたはそのエステル形態である、請求項53に 記載の造影剤。 56.前記PPBMが少なくとも13個の炭素原子を含む、請求項53に記載の造影剤 。 57.前記PPBMが少なくとも18個の炭素原子を含む、請求項53に記載の造影剤 。 58.前記PPBMが少なくとも2.0のlogPの寄与を有する、請求項53に記載の造 影剤。 59.前記PPBMが少なくとも3.0のlogPの寄与を有する、請求項53に記載の造 影剤。 60.前記PPBMが少なくとも4.0のlogPの寄与を有する、請求項53に記載の造 影剤。 61.以下を含む、診断用画像化造影剤: ここで、Mは原子番号21〜29、42、44または57〜83を有する金属イオンであり 、 R1〜R11およびR16は、同じであっても異なってもよく、かつH、PPBM、BHEM およびC1-6アルキルからなる群より選択され、 ただし、R1〜R11またはR16の少なくとも1つはPPBMであり、 ただしまた、R1〜R11またはR16の少なくとも1つはBHEMであり、 R12、R13およびR14は、同じであっても異なってもよく、かつO-およびN(H)R17 からなる群より選択され、 R15はH、CH2CH(OH)CH3、ヒドロキシアルキルまたはCH(R16)COR12であり、 R17はHまたはC1-6アルキルであり、 BHEMは、2つ以上の正電荷を帯びた水素原子、またはIEMに共有結合または 配位共有結合することにより部分的または完全に中和され得ない2つ以上の孤立 電子対を有する血液半減期延長部分であり、そしてスルホン、尿素、チオ尿素、 アミン、スルホンアミド、カルバメート、ペプチド、エステル、カルボネート、 アセタール、COO-またはエステル形態、SO3 -またはエステル形態および ここで、ZはP、W、MoまたはSであり、 Y1、Y2はOまたはSであり、 Y3、Y4は、O、Sであるか、または存在せず、 R2は、H、C1-6アルキルであるか、または存在せず、 PPBMは、少なくとも7個の炭素原子を含む血漿タンパク質結合部分である。 62.前記MがGd(III)、Fe(III)、Mn(II)、Mn(III)、Cr(III)、Cu(II)、Dy(III) 、Tb(III)、Ho(III)、Er(III)およびEu(III)からなる群より選択される、請求項 61に記載の造影剤。 63.前記MがGd(III)である、請求項62に記載の造影剤。 64.前記BHEMが、COO-またはエステル形態、SO3 -またはエステル形態および ここで、ZがP、W、MoまたはSであり、 Y1、Y2がOまたはSであり、 Y3、Y4が、O、Sであるか、または存在せず、 R2が、H、C1-6アルキルであるか、または存在しない、 請求項61〜63のいずれか1つに記載の造影剤。 65.前記PPBMが少なくとも13個の炭素原子を含む、請求項61〜63のいずれ か1つに記載の造影剤。 66.前記PPBMが少なくとも18個の炭素原子を含む、請求項61〜63のいずれ か1つに記載の造影剤。 67.前記PPBMが少なくとも2.0のlogPの寄与を有する、請求項61〜63のい ずれか1つに記載の造影剤。 68.前記PPBMが少なくとも3.0のlogPの寄与を有する、請求項61〜63のい ずれか1つに記載の造影剤。 69.前記PPBMが少なくとも4.0のlogPの寄与を有する、請求項61〜63のい ずれか1つに記載の造影剤。 70.以下の式を有する化合物: 71.以下の式を有する化合物: 72.以下の式を有する化合物: 73.以下の式を有する化合物: 74.以下の式を有する化合物: 75.以下の式を有する化合物: 76.以下の式を有する化合物: 77.以下の式を有する化合物: 78.以下の式を有する化合物: 79.以下の式を有する化合物: 80.以下の式を有する化合物: 81.以下の式を有する化合物: 82.以下の式を有する化合物: 83.以下の式を有する化合物: ここで、PPBMは、少なくとも7個の炭素原子を有する血漿タンパク質結合部分 であり、そしてnは1〜4に等しくあり得る。 84.以下の式を有する化合物: ここで、PPBMは、少なくとも7個の炭素原子を有する血漿タンパク質結合部分 であり、そしてnは1〜4に等しくあり得る。 85.以下の式を有する化合物: ここで、nは1〜4に等しくあり得る。 86.以下の式を有する化合物: ここで、nは1〜4に等しくあり得る。 87.以下の式を有する化合物: ここでnは1〜4に等しくあり得る。 88.以下の式を有する化合物: ここで、nは1〜4に等しくあり得る。 89.以下の式を有する化合物: ここで、nは1〜4に等しくあり得る。 90.以下の式を有する化合物: ここで、Rは脂肪族基および/または少なくとも1個のアリール環を含む。 91.Rが疎水性アミノ酸残基および/または疎水性または親水性の末端基があ ってもなくてもよい置換基を含有するペプチドを含む、請求項90に記載の化合 物。 92.以下の式を有する化合物: ここで、Rは脂肪族基および/または少なくとも1個のアリール環を含む。 93.Rが疎水性アミノ酸残基および/または疎水性または親水性の末端基があ ってもなくてもよい置換基を含有するペプチドを含む、請求項92に記載の化合 物。 94.請求項1、37、45、53または61のいずれか1つに記載の造影剤の 診断的有効量を投与する工程を包含する、生物学的構成成分のMRI画像化方法。 95.請求項1、37、45、53または61のいずれか1つに記載の造影剤の 診断的有効量を投与する工程を包含する、生物学的構成成分の超音波画像化方法 。 96.請求項1、37、45、53または61のいずれか1つに記載の造影剤の 診断的有効量を投与する工程を包含する、生物学的構成成分のX線画像化方法。 97.請求項1、37、45、53または61のいずれか1つに記載の造影剤の 診断的有効量を投与する工程を包含する、生物学的構成成分の核放射性医薬品画 像化方法。 98.請求項1、37、45、53または61のいずれか1つに記載の造影剤の 診断的有効量を投与する工程を包含する、生物学的構成成分の紫外/可視/赤外光 画像化方法。 99.請求項1、37、45、53または61のいずれか1つに記載の造影剤お よびキャリア、アジュバントまたはビヒクルを含む、薬学的組成物。 100.遊離の有機リガンドまたは薬学的に受容可能なその塩をさらに含む、請 求項99に記載の薬学的組成物。 101.遊離の有機リガンドまたはそのカルシウム、ナトリウム、メグルミンも しくは組み合わせの塩をさらに含む、請求項99に記載の薬学的組成物。 102.以下の工程: a)造影剤を含有するシリンジ内に、患者の血液を取り込む工程; b)シリンジ中で該血液と造影剤とを混合する工程;および c)該患者に該混合物を再び注射する工程; を包含する、請求項1、37、45、53または61のいずれか1つに記載の造 影剤を投与する方法。
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2001008924A (ja) * | 1999-06-30 | 2001-01-16 | Eizo Mori | X線診断システム |
WO2008108163A1 (ja) * | 2007-03-06 | 2008-09-12 | Konica Minolta Holdings, Inc. | ガドリニウム化合物及びmri用造影剤 |
WO2011046007A1 (ja) | 2009-10-15 | 2011-04-21 | 国立大学法人徳島大学 | ジエチレントリアミン五酢酸誘導体の製造方法およびジエチレントリアミン五酢酸誘導体 |
US8487126B2 (en) | 2009-10-15 | 2013-07-16 | The University Of Tokushima | Process for preparation of diethylenetriaminepentaacetic acid derivative, and diethylenetriaminepentaacetic acid derivative |
JP2016514151A (ja) * | 2013-03-13 | 2016-05-19 | ランセウス メディカル イメージング, インコーポレイテッド | ガドフォスベセット三ナトリウム一水和物の製造方法 |
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