JPH06508364A - ガス充填リポソーム及び超音波造影剤としてのそれらの使用 - Google Patents
ガス充填リポソーム及び超音波造影剤としてのそれらの使用Info
- Publication number
- JPH06508364A JPH06508364A JP5500847A JP50084793A JPH06508364A JP H06508364 A JPH06508364 A JP H06508364A JP 5500847 A JP5500847 A JP 5500847A JP 50084793 A JP50084793 A JP 50084793A JP H06508364 A JPH06508364 A JP H06508364A
- Authority
- JP
- Japan
- Prior art keywords
- liposomes
- liposome
- gas
- container
- patient
- 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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Abstract
Description
Claims (61)
- 1.真空乾燥ガス注入方法によって製造された、ガス充填リポソームを含んで成 る、超音波イメージングのための造影剤。
- 2.該リポソームが、脂肪酸、リソ脂質、ジパルミトイルホスファチジルコリン 、ホスファチジルコリン、ホスファチジン酸、スフィンゴミエリン、コレステロ ール、コレステロールヘミスクシネート、トコフェロールヘミスクシネート、ホ スファチジルエタノールアミン、ホスファチジルイノシトール、リソ脂質、スフ ィンゴミエリン、グリコスフィンゴ脂質、グルコ脂質、グリコ脂質、スルファチ ド、エーテル及びエステル結合された脂肪酸を有する脂質、並びに重合された脂 質から成る群から選ばれた脂質材料を含んで成る、請求の範囲1記載の造影剤。
- 3.該リポソームがジパルミトイルホスファチジルコリンを含んで成る、請求の 範囲2記載の造影剤。
- 4.該リポソームが、空気、窒素、二酸化炭素、酸素、アルゴン、キセノン、へ リウム及びネオンから成る群から選ばれたガスによって満たされている、請求の 範囲1記載の造影剤。
- 5.該リポソームが窒素ガスによって満たされている、請求の範囲4記載の造影 剤。
- 6.該リポソームが水性媒体中に懸濁されて貯蔵される、請求の範囲1記載の造 影剤。
- 7.該リポソームが乾燥して貯蔵される、請求の範囲1記載の造影剤。
- 8.該リポソームが約3週間より長い安定性を有する、請求の範囲1記載の造影 剤。
- 9.該リポソームが約2dBより大きい反射率を有する、請求の範囲1記載の造 影剤。
- 10.該リポソームが約2dB〜約20dBの反射率を有する、請求の範囲9記 載の造影剤。
- 11.その内部に液体が実質的にない、ガス充填リポソームを含んで成る、超音 波イメージングのための造影剤。
- 12.該リポソームが、脂肪酸、リソ脂質、ジパルミトイルホスファチジルコリ ン、ホスファチジルコリン、ホスファチジン酸、スフィンゴミエリン、コレステ ロール、コレステロールヘミスクシネート、トコフェロールヘミスクシネート、 ホスファチジルエタノールアミン、ホスファチジルイノシトール、リソ脂質、ス フィンゴミエリン、グリコスフィンゴ脂質、グルコ脂質、グリコ脂質、スルファ チド、エーテル及びエステル結合された脂肪酸を有する脂質、並びに重合された 脂質から成る群から選ばれた脂質材料を含んで成る、請求の範囲11記載の造影 剤。
- 13.該リポソームがジパルミトイルホスファチジルコリンを含んで成る、請求 の範囲12記載の造影剤。
- 14.該リポソームが、空気、窒素、二酸化炭素、酸素、アルゴン、キセノン、 へリウム及びネオンから成る群から選ばれたガスによって満たされている、請求 の範囲11記載の造影剤。
- 15.該リポソームが窒素ガスによって満たされている、請求の範囲14記載の 造影剤。
- 16.該リポソームが水性媒体中に懸濁されて貯蔵される、請求の範囲11記載 の造影剤。
- 17.該リポソームが乾燥して貯蔵される、請求の範囲11記載の造影剤。
- 18.該リポソームが約3週間より長い貯蔵寿命安定性を有する、請求の範囲1 1記載の造影剤。
- 19.該リポソームが約2dBより大きい反射率を有する、請求の範囲11記載 の造影剤。
- 20.該リポソームが約2dB〜約20dBの反射率を有する、請求の範囲19 記載の造影剤。
- 21.(i)リポソームを陰圧下に置く工程、(ii)該リポソームから実質的 にすべての液体を除去するのに十分な時間の間、該リポソームを該陰圧下でイン キユベートする工程、及び(iii)周囲圧力に到達するまで該リポソーム中に ガスを注入する工程を含んで成る、超音波イメージング用造影剤の製造方法。
- 22.工程(i)に先立ってそしてその間、該リポソームを約−10℃〜約−2 0℃の温度に冷却せしめること、工程(ii)の間、該リポソームを約10℃〜 約20℃の温度に加温せしめること、及び工程(出)の間、該リポソームを周囲 温度に加温せしめることを更に含んで成る、請求の範囲21記載の方法。
- 23.該陰圧が約700mmHg〜約760mmHgでありそして約24〜約7 2時間かけられる、請求の範囲21記載の方法。
- 24.該ガスを約4〜約8時間の期間にわたって該リポソーム中に注入する、請 求の範囲21記載の方法。
- 25.該ガスが、空気、窒素、二酸化炭素、酸素、アルゴン、キセノン、ネオン 及びへリウムから成る群から選ばれる、請求の範囲21記載の方法。
- 26.該ガスが窒素である、請求の範囲25記載の方法。
- 27.工程(iii)の後で、該リポソームを選ばれた細孔サイズの少なくとも 一種のフィルターを通して押出すことを更に含んで成る、請求の範囲21記載の 方法。
- 28.(i)リポソームを約−10℃〜約−20℃の温度に冷却せしめる工程、 (ii)該リポソームを約700mmHg〜約760mmHgの陰圧下に置く工 程、 (iii)該リポソームを約10℃〜約20℃の温度に加温せしめながら、該リ ポソームを該陰圧下で約24〜約72時間インキュベートして該リポソームから 実質的にすべての液体を除去する工程、及び(iv)該リポソームを周囲温度に 加温せしめながら、周囲圧力に到達するまで約4〜約8時間の期間にわたって該 リポソーム中にガスを注入する工程、 を含んで成る、超音波イメージング用造影剤の製造方法。
- 29.該ガスが、空気、窒素、二酸化炭素、酸素、アルゴン、キセノン、ネオン 及びへリウムから成る群から選ばれる、請求の範囲28記載の方法。
- 30.該ガスが窒素である、請求の範囲29記載の方法。
- 31.工程(iv)の後で、該リポソームを選ばれた細孔サイズの少なくとも一 種のフィルターを通して押出すことを更に含有して成る、請求の範囲28記載の 方法。
- 32.(i)リポソームを入れるための容器、(ii)この容器中に入れられた リポソームから液体を引き出すために容器に陰圧をかけるための手段、 (iii)陰圧をかける手段を容器に接続する導管(この導管は液体の流れを方 向付ける)、及び (iv)容器中に入れられたリポソーム中にガスを導入するための手段を含んで 成る、超音波イメージング用造影剤の製造装置。
- 33.陰圧をかける手段が真空ポンプである、請求の範囲32記載の装置。
- 34.容器中に入れられたリポソームを冷却するための手段を更に含んで成る、 請求の範囲32記載の装置。
- 35.前記冷却手段が容器中に入れられたリポソームを約−10℃〜約−20℃ に冷却するための手段を有する、請求の範囲34記載の装置。
- 36.前記冷却手段がアイスバスを含有して成る、請求の範囲35記載の装置。
- 37.前記導管中を流れる液体を収集するための手段を更に含んで成る、請求の 範囲32記載の装置。
- 38.前記収集手段がトラップである、請求の範囲37記載の装置。
- 39.トラップを冷却するための手段を更に含んで成る、請求の範囲38記載の 装置。
- 40.トラップがそれを通して流れる流体を方向付けるのに適した第一及び第二 部材を含んで成り、これらの部材が相互に、そして導管と流れを連絡していて、 第二部材が第一部材の回りに螺旋状に配置されていて、そしてトラップが、第一 及び第二部材の少なくとも一部を取り囲む氷浴を含んで成る冷却手段を含んで成 る、請求の範囲38記載の装置。
- 41.(i)リポソームを入れるための容器、(ii)この容器中に入れられた リポソームを冷却するための手段、(iii)この容器中に入れられたリポソー ムから液体を引き出すために容器に陰圧をかけるための手段、 (iv)陰圧をかける手段を容器に接続する導管(この導管は液体の流れを方向 付ける)、 (v)導管中を流れる液体を収集するための手段、及び(vi)容器中に入れら れたリポソーム中にガスを導入するための手段を含んで成る、超音波イメージン グのための造影剤を製造するための装置。
- 42.患者の内部の身体の部位の画像を提供する方法であって、(a)真空乾燥 ガス注入方法によって製造された、ガス充填リポソームを含有して成る造影剤を 患者に投与すること、及び(b)超音波イメージングを使用して患者を走査して 前記部位の可視画像を得ること を含んで成る方法。
- 43.患者を、患者の左心の領域で走査する、請求の範囲42記載の方法。
- 44.患者の内部の身体の部位の画像を提供する方法であって、(a)その内部 に液体が実質的にない、ガス充填リポソームを含んで成る造影剤を患者に投与す ること、及び(b)超音波イメージングを使用して患者を走査して前記部位の可 視画像を得ること を含んで成る方法。
- 45.患者を、患者の左心の領域で走査する、請求の範囲44記載の方法。
- 46.患者の中の疾患組織の存在を診断するための方法であって、(i)真空乾 燥ガス注入方法によって製造された、ガス充填リポソームを含んで成る造影剤を 患者に投与すること、及び(ii)超音波イメージングを使用して患者を走査し て患者の中に存在しうる疾患組織の可視画像を得ること を含んで成る方法。
- 47.患者を、患者の左心の領域で走査する、請求の範囲46記載の方法。
- 48.患者の中の疾患組織の存在を診断するための方法であって、(i)その内 部中に液体が実質的にない、ガス充填リポソームを含んで成る造影剤を患者に投 与すること、及び(ii)超音波イメージングを使用して患者を走査して患者の 中に存在しうる疾患組織の可視画像を得ること を含んで成る方法。
- 49.患者を、患者の左心の領域で走査する、請求の範囲48記載の方法。
- 50.真空乾燥ガス注入方法によって製造された、ガス充填リポソームを含んで 成る超音波イメージングのためのキット。
- 51.慣用の超音波イメージング構成要素を更に含んで成る、請求の範囲50記 載のキット。
- 52.その内部に液体が実質的にない、ガス充填リポソームを含んで成る超音波 イメージングのためのキット。
- 53.慣用の超音波イメージング構成要素を更に含んで成る、請求の範囲52記 載のキット。
- 54.請求の範囲21記載の方法によって製造された生成物。
- 55.請求の範囲28記載の方法によって製造された生成物。
- 56.(i)リポソームを陰圧下に置く工程、(ii)該リポソームから実質的 にすべての液体を除去するのに十分な時間の間、該リポソームを該陰圧下でイン キユベートする工程、及び(iii)周囲圧力に到達するまで該リポソーム中に ガスを注入する工程、を含んで成る、ガス充填リポソームの製造方法。
- 57.(i)リポソームを約−10℃〜約−20℃の温度に冷却せしめる工程、 (ii)該リポソームを約700mmHg〜約760mmHgの陰圧下に置く工 程、 (iii)該リポソームを約10℃〜約20℃の温度に加温せしめながら、該リ ポソームを該陰圧下でインキユベートして該リポソームから実質的にすべての液 体を除去する工程、及び (iv)該リポソームを周囲温度に加温せしめながら、周囲圧力に到達するまで 約4〜約8時間の期間にわたって該リポソーム中にガスを注入する工程、 を含んで成る、ガス充填リポソームの製造方法。
- 58.(i)リポソームを入れるための容器、(ii)この容器中に入れられた リポソームから液体を引き出すために容器に陰圧をかけるための手段、 (iii)陰圧をかける手段を容器に接続する導管(この導管は該液体の流れを 方向付ける)、及び (iv)容器中に入れられたリポソーム中にガスを導入するための手段を含んで 成る、ガス充填リポソームの製造装置。
- 59.(i)リポソームを入れるための容器、(ii)この容器中に入れられた リポソームを冷却するための手段、(iii)この容器中に入れられたリポソー ムから液体を引き出すために容器に陰圧をかけるための手段、 (iv)陰圧をかける手段を容器に接続する導管(この導管は液体の流れを方向 付ける)、 (v)導管中を流れる液体を収集するための手段、及び(vi)容器中に入れら れたリポソーム中にガスを導入するための手段を含んで成る、ガス充填リポソー ムの製造装置。
- 60.請求の範囲56記載の方法によって製造された生成物。
- 61.請求の範囲57記載の方法によって製造された生成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US07/717,084 US5228446A (en) | 1989-12-22 | 1991-06-18 | Gas filled liposomes and their use as ultrasonic contrast agents |
US717,084 | 1991-06-18 | ||
PCT/US1992/002615 WO1992022247A1 (en) | 1991-06-18 | 1992-03-31 | Gas filled liposomes and their use as ultrasonic contrast agents |
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JP3456584B2 JP3456584B2 (ja) | 2003-10-14 |
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US (1) | US5228446A (ja) |
EP (1) | EP0616508B2 (ja) |
JP (1) | JP3456584B2 (ja) |
AT (1) | ATE203148T1 (ja) |
AU (1) | AU667471B2 (ja) |
DE (1) | DE69231950T3 (ja) |
DK (1) | DK0616508T4 (ja) |
ES (1) | ES2159280T5 (ja) |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019198461A1 (ja) * | 2018-04-10 | 2019-10-17 | 国立大学法人千葉大学 | 超音波造影及び近赤外蛍光造影の両方が可能な造影剤 |
Families Citing this family (103)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5305757A (en) | 1989-12-22 | 1994-04-26 | Unger Evan C | Gas filled liposomes and their use as ultrasonic contrast agents |
US5352435A (en) * | 1989-12-22 | 1994-10-04 | Unger Evan C | Ionophore containing liposomes for ultrasound imaging |
US6551576B1 (en) | 1989-12-22 | 2003-04-22 | Bristol-Myers Squibb Medical Imaging, Inc. | Container with multi-phase composition for use in diagnostic and therapeutic applications |
US5733572A (en) | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
US5580575A (en) | 1989-12-22 | 1996-12-03 | Imarx Pharmaceutical Corp. | Therapeutic drug delivery systems |
US5922304A (en) | 1989-12-22 | 1999-07-13 | Imarx Pharmaceutical Corp. | Gaseous precursor filled microspheres as magnetic resonance imaging contrast agents |
US5705187A (en) * | 1989-12-22 | 1998-01-06 | Imarx Pharmaceutical Corp. | Compositions of lipids and stabilizing materials |
US5773024A (en) * | 1989-12-22 | 1998-06-30 | Imarx Pharmaceutical Corp. | Container with multi-phase composition for use in diagnostic and therapeutic applications |
US6088613A (en) | 1989-12-22 | 2000-07-11 | Imarx Pharmaceutical Corp. | Method of magnetic resonance focused surgical and therapeutic ultrasound |
US5469854A (en) * | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5776429A (en) | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US6146657A (en) | 1989-12-22 | 2000-11-14 | Imarx Pharmaceutical Corp. | Gas-filled lipid spheres for use in diagnostic and therapeutic applications |
US6001335A (en) | 1989-12-22 | 1999-12-14 | Imarx Pharmaceutical Corp. | Contrasting agents for ultrasonic imaging and methods for preparing the same |
US5542935A (en) | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US5656211A (en) * | 1989-12-22 | 1997-08-12 | Imarx Pharmaceutical Corp. | Apparatus and method for making gas-filled vesicles of optimal size |
USRE39146E1 (en) | 1990-04-02 | 2006-06-27 | Bracco International B.V. | Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof |
US20040208826A1 (en) * | 1990-04-02 | 2004-10-21 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US6989141B2 (en) * | 1990-05-18 | 2006-01-24 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
IN172208B (ja) * | 1990-04-02 | 1993-05-01 | Sint Sa | |
US6613306B1 (en) | 1990-04-02 | 2003-09-02 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US20010024638A1 (en) * | 1992-11-02 | 2001-09-27 | Michel Schneider | Stable microbubble suspensions as enhancement agents for ultrasound echography and dry formulations thereof |
US20030194376A1 (en) * | 1990-05-18 | 2003-10-16 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
AU636481B2 (en) * | 1990-05-18 | 1993-04-29 | Bracco International B.V. | Polymeric gas or air filled microballoons usable as suspensions in liquid carriers for ultrasonic echography |
JP3218637B2 (ja) * | 1990-07-26 | 2001-10-15 | 大正製薬株式会社 | 安定なリポソーム水懸濁液 |
GB9106686D0 (en) * | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
US5205290A (en) | 1991-04-05 | 1993-04-27 | Unger Evan C | Low density microspheres and their use as contrast agents for computed tomography |
US5874062A (en) | 1991-04-05 | 1999-02-23 | Imarx Pharmaceutical Corp. | Methods of computed tomography using perfluorocarbon gaseous filled microspheres as contrast agents |
US5409688A (en) * | 1991-09-17 | 1995-04-25 | Sonus Pharmaceuticals, Inc. | Gaseous ultrasound contrast media |
JP3231768B2 (ja) * | 1991-09-17 | 2001-11-26 | ソーナス ファーマシューティカルス,インコーポレイテッド | 気体状超音波造影剤及び超音波造影剤として使用する気体の選定方法 |
MX9205298A (es) * | 1991-09-17 | 1993-05-01 | Steven Carl Quay | Medios gaseosos de contraste de ultrasonido y metodo para seleccionar gases para usarse como medios de contraste de ultrasonido |
GB9200388D0 (en) * | 1992-01-09 | 1992-02-26 | Nycomed As | Improvements in or relating to contrast agents |
IL104084A (en) | 1992-01-24 | 1996-09-12 | Bracco Int Bv | Sustainable aqueous suspensions of pressure-resistant and gas-filled blisters, their preparation, and contrast agents containing them |
EP0665756A1 (de) * | 1992-10-16 | 1995-08-09 | SACHSE, Andreas | Verfahren und vorrichtung zur herstellung flüssiger, disperser systeme |
IL108416A (en) | 1993-01-25 | 1998-10-30 | Sonus Pharma Inc | Colloids with phase difference as contrast ultrasound agents |
US5558855A (en) * | 1993-01-25 | 1996-09-24 | Sonus Pharmaceuticals | Phase shift colloids as ultrasound contrast agents |
PL176116B1 (pl) * | 1993-01-25 | 1999-04-30 | Sonus Pharma Inc | Środek kontrastowy do ultrasonografii i sposób wytwarzania środka kontrastowego do ultrasonografii |
US5798091A (en) | 1993-07-30 | 1998-08-25 | Alliance Pharmaceutical Corp. | Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement |
WO1995003835A1 (en) | 1993-07-30 | 1995-02-09 | Alliance Pharmaceutical Corp. | Stabilized microbubble compositions for ultrasound |
US5433204A (en) * | 1993-11-16 | 1995-07-18 | Camilla Olson | Method of assessing placentation |
RU2138293C1 (ru) | 1993-12-15 | 1999-09-27 | Бракко Рисерч С.А. | Контрастные вещества для ультразвуковой эхографии, контрастные средства, содержащие эти вещества, и способы их приготовления |
IL113139A0 (en) * | 1994-03-28 | 1995-06-29 | Nycomed Imaging As | Diagnostic compositions comprising imaging agents encapsulated in liposomes |
US5736121A (en) | 1994-05-23 | 1998-04-07 | Imarx Pharmaceutical Corp. | Stabilized homogenous suspensions as computed tomography contrast agents |
US5540909A (en) * | 1994-09-28 | 1996-07-30 | Alliance Pharmaceutical Corp. | Harmonic ultrasound imaging with microbubbles |
US6743779B1 (en) | 1994-11-29 | 2004-06-01 | Imarx Pharmaceutical Corp. | Methods for delivering compounds into a cell |
IL116328A (en) † | 1994-12-16 | 1999-09-22 | Bracco Research Sa | Frozen suspension of gas microbubbles in frozen aqueous carrier for use as contrast agent in ultrasonic imaging |
US5830430A (en) | 1995-02-21 | 1998-11-03 | Imarx Pharmaceutical Corp. | Cationic lipids and the use thereof |
US5997898A (en) | 1995-06-06 | 1999-12-07 | Imarx Pharmaceutical Corp. | Stabilized compositions of fluorinated amphiphiles for methods of therapeutic delivery |
US5804162A (en) | 1995-06-07 | 1998-09-08 | Alliance Pharmaceutical Corp. | Gas emulsions stabilized with fluorinated ethers having low Ostwald coefficients |
US5897851A (en) * | 1995-06-07 | 1999-04-27 | Sonus Pharmaceuticals, Inc. | Nucleation and activation of a liquid-in-liquid emulsion for use in ultrasound imaging |
WO2004073750A1 (en) * | 1995-06-07 | 2004-09-02 | Harald Dugstad | Improvements in or relating to contrast agents |
US6033645A (en) | 1996-06-19 | 2000-03-07 | Unger; Evan C. | Methods for diagnostic imaging by regulating the administration rate of a contrast agent |
US6231834B1 (en) | 1995-06-07 | 2001-05-15 | Imarx Pharmaceutical Corp. | Methods for ultrasound imaging involving the use of a contrast agent and multiple images and processing of same |
US6139819A (en) | 1995-06-07 | 2000-10-31 | Imarx Pharmaceutical Corp. | Targeted contrast agents for diagnostic and therapeutic use |
US6521211B1 (en) | 1995-06-07 | 2003-02-18 | Bristol-Myers Squibb Medical Imaging, Inc. | Methods of imaging and treatment with targeted compositions |
US5611344A (en) * | 1996-03-05 | 1997-03-18 | Acusphere, Inc. | Microencapsulated fluorinated gases for use as imaging agents |
PT904113E (pt) * | 1996-03-05 | 2004-09-30 | Acusphere Inc | Gases fluorados microencapsulados para utilizacao como agentes de aquisicao de imagem |
EP0935415B1 (en) | 1996-05-01 | 2006-11-22 | Imarx Pharmaceutical Corp. | In vitro methods for delivering nucleic acids into a cell |
US6414139B1 (en) | 1996-09-03 | 2002-07-02 | Imarx Therapeutics, Inc. | Silicon amphiphilic compounds and the use thereof |
US5846517A (en) | 1996-09-11 | 1998-12-08 | Imarx Pharmaceutical Corp. | Methods for diagnostic imaging using a renal contrast agent and a vasodilator |
EP0977597B1 (en) | 1996-09-11 | 2003-01-15 | Imarx Pharmaceutical Corp. | Improved methods for diagnostic imaging using a contrast agent and a vasodilator |
US6143276A (en) * | 1997-03-21 | 2000-11-07 | Imarx Pharmaceutical Corp. | Methods for delivering bioactive agents to regions of elevated temperatures |
US6537246B1 (en) | 1997-06-18 | 2003-03-25 | Imarx Therapeutics, Inc. | Oxygen delivery agents and uses for the same |
US6120751A (en) | 1997-03-21 | 2000-09-19 | Imarx Pharmaceutical Corp. | Charged lipids and uses for the same |
US6090800A (en) | 1997-05-06 | 2000-07-18 | Imarx Pharmaceutical Corp. | Lipid soluble steroid prodrugs |
US6416740B1 (en) | 1997-05-13 | 2002-07-09 | Bristol-Myers Squibb Medical Imaging, Inc. | Acoustically active drug delivery systems |
US6548047B1 (en) | 1997-09-15 | 2003-04-15 | Bristol-Myers Squibb Medical Imaging, Inc. | Thermal preactivation of gaseous precursor filled compositions |
US6123923A (en) | 1997-12-18 | 2000-09-26 | Imarx Pharmaceutical Corp. | Optoacoustic contrast agents and methods for their use |
US20010003580A1 (en) | 1998-01-14 | 2001-06-14 | Poh K. Hui | Preparation of a lipid blend and a phospholipid suspension containing the lipid blend |
GB9808599D0 (en) * | 1998-04-22 | 1998-06-24 | Nycomed Imaging As | Improvements in or realting to contrast agents |
GB9809084D0 (en) * | 1998-04-28 | 1998-06-24 | Nycomed Imaging As | Improvements in or relating to diagnostic/therapeutic agents |
US6548048B1 (en) | 1998-04-28 | 2003-04-15 | Amersham Health As | Lipopeptide stabilized microbubbles as diagnostic/therapeutic agents |
WO2000038546A1 (en) * | 1998-12-23 | 2000-07-06 | Unilever N.V. | Pourable water and oil containing emulsions comprising gas bubbles |
US6572840B1 (en) | 1999-07-28 | 2003-06-03 | Bristol-Myers Squibb Pharma Company | Stable microbubbles comprised of a perfluoropropane encapsulated lipid moiety for use as an ultrasound contrast agent |
EP2279757A3 (en) | 2000-06-02 | 2011-08-03 | Bracco Suisse SA | Compounds for targeting endothelial cells |
NO20004795D0 (no) * | 2000-09-26 | 2000-09-26 | Nycomed Imaging As | Peptidbaserte forbindelser |
US7344702B2 (en) * | 2004-02-13 | 2008-03-18 | Bristol-Myers Squibb Pharma Company | Contrast agents for myocardial perfusion imaging |
WO2004069153A2 (en) * | 2003-01-27 | 2004-08-19 | Medrad, Inc. | Apparatus, system and method for generating bubbles on demand |
CA2532324A1 (en) * | 2002-07-11 | 2004-01-22 | Targeson, Llc | Microbubble compositions, and methods for preparing and using same |
US20040175329A1 (en) * | 2003-03-07 | 2004-09-09 | Fisher John Steele | Method for continuous visualization of a body lumen |
US7803352B2 (en) * | 2003-03-07 | 2010-09-28 | John Steele Fisher | Method for continuous visualization of a blood clot or plaque in body lumen |
US7358226B2 (en) * | 2003-08-27 | 2008-04-15 | The Regents Of The University Of California | Ultrasonic concentration of drug delivery capsules |
US20050106101A1 (en) * | 2003-10-31 | 2005-05-19 | Ajay Purohit | Novel chemical agents comprising an adenosine moiety or an adenosine analog moiety and an imaging moiety and methods of their use |
US7485283B2 (en) | 2004-04-28 | 2009-02-03 | Lantheus Medical Imaging | Contrast agents for myocardial perfusion imaging |
US8012457B2 (en) | 2004-06-04 | 2011-09-06 | Acusphere, Inc. | Ultrasound contrast agent dosage formulation |
US20060083681A1 (en) * | 2004-10-18 | 2006-04-20 | Ajay Purohit | Compounds for myocardial perfusion imaging |
US7824659B2 (en) | 2005-08-10 | 2010-11-02 | Lantheus Medical Imaging, Inc. | Methods of making radiolabeled tracers and precursors thereof |
US20070140973A1 (en) * | 2005-12-15 | 2007-06-21 | Bristol-Myers Squibb Pharma Company | Contrast agents for myocardium perfusion imaging |
EP1991577A2 (en) | 2006-01-31 | 2008-11-19 | Parkinson, John F. | Modulation of mdl-1 activity for treatment of inflammatory disease |
CA2967254C (en) | 2008-02-29 | 2019-03-26 | Lantheus Medical Imaging, Inc. | Contrast agents for applications including imaging cancer |
GB0811856D0 (en) | 2008-06-27 | 2008-07-30 | Ucl Business Plc | Magnetic microbubbles, methods of preparing them and their uses |
US20110195501A1 (en) * | 2008-08-06 | 2011-08-11 | Pangu Gautam D | Ultrasonically induced release from polymer vesicles |
EP2419096B1 (en) | 2009-04-15 | 2019-11-13 | Lantheus Medical Imaging, Inc. | Stabilization of radiopharmaceutical compositions using ascorbic acid |
US10258563B2 (en) | 2009-04-20 | 2019-04-16 | Drexel University | Encapsulation of microbubbles within the aqueous core of microcapsules |
KR102438133B1 (ko) | 2010-02-08 | 2022-08-31 | 랜티우스 메디컬 이메징, 인크. | 조영제 및 이의 중간체를 합성하는 방법 및 장치 |
CN103565745A (zh) | 2012-08-10 | 2014-02-12 | 德克萨斯州大学系统董事会 | 用于治疗中风的神经保护性脂质体组合物和方法 |
AU2013203000B9 (en) | 2012-08-10 | 2017-02-02 | Lantheus Medical Imaging, Inc. | Compositions, methods, and systems for the synthesis and use of imaging agents |
US10017551B2 (en) | 2013-03-15 | 2018-07-10 | The Regents Of The University Of California | Peptides having reduced toxicity that stimulate cholesterol efflux |
AU2014233018A1 (en) | 2013-03-15 | 2015-10-01 | The Board Of Regents Of The University Of Texas System | Liquids rich in noble gas and methods of their preparation and use |
IL252705B2 (en) | 2014-12-31 | 2023-03-01 | Lantheus Medical Imaging Inc | Fat-wrapped gas microsphere preparations and related methods |
AU2017260532A1 (en) | 2016-05-04 | 2018-11-22 | Lantheus Medical Imaging, Inc. | Methods and devices for preparation of ultrasound contrast agents |
US9789210B1 (en) | 2016-07-06 | 2017-10-17 | Lantheus Medical Imaging, Inc. | Methods for making ultrasound contrast agents |
EP3412303A1 (en) | 2017-06-08 | 2018-12-12 | Medizinische Universität Innsbruck | Improved pharmacokinetics and cholecystokinin-2 receptor (cck2r) targeting for diagnosis and therapy |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4162282A (en) * | 1976-04-22 | 1979-07-24 | Coulter Electronics, Inc. | Method for producing uniform particles |
US4351603A (en) * | 1978-08-28 | 1982-09-28 | Ricoh Company, Ltd. | Electronic copying apparatus |
US4310505A (en) * | 1979-11-08 | 1982-01-12 | California Institute Of Technology | Lipid vesicles bearing carbohydrate surfaces as lymphatic directed vehicles for therapeutic and diagnostic substances |
SE7909819L (sv) * | 1979-11-28 | 1981-05-29 | Karl Thore Sterner | Anordning for separering av exkrementer och foderrester i en fiskodlingsbehallare |
US4657756A (en) * | 1980-11-17 | 1987-04-14 | Schering Aktiengesellschaft | Microbubble precursors and apparatus for their production and use |
US4533254A (en) * | 1981-04-17 | 1985-08-06 | Biotechnology Development Corporation | Apparatus for forming emulsions |
EP0068961A3 (fr) * | 1981-06-26 | 1983-02-02 | Thomson-Csf | Dispositif d'échauffement localisé de tissus biologiques |
DE3374522D1 (ja) * | 1982-10-26 | 1987-12-23 | University Of Aberdeen | |
US4900540A (en) * | 1983-06-20 | 1990-02-13 | Trustees Of The University Of Massachusetts | Lipisomes containing gas for ultrasound detection |
FR2563725B1 (fr) * | 1984-05-03 | 1988-07-15 | Dory Jacques | Appareil d'examen et de localisation de tumeurs par ultrasons muni d'un dispositif de traitement localise par hyperthermie |
GB8407557D0 (en) * | 1984-03-23 | 1984-05-02 | Hayward J A | Polymeric lipsomes |
US4728575A (en) * | 1984-04-27 | 1988-03-01 | Vestar, Inc. | Contrast agents for NMR imaging |
US4620546A (en) * | 1984-06-30 | 1986-11-04 | Kabushiki Kaisha Toshiba | Ultrasound hyperthermia apparatus |
US4880635B1 (en) * | 1984-08-08 | 1996-07-02 | Liposome Company | Dehydrated liposomes |
US4921706A (en) * | 1984-11-20 | 1990-05-01 | Massachusetts Institute Of Technology | Unilamellar lipid vesicles and method for their formation |
US4830858A (en) * | 1985-02-11 | 1989-05-16 | E. R. Squibb & Sons, Inc. | Spray-drying method for preparing liposomes and products produced thereby |
US4689986A (en) * | 1985-03-13 | 1987-09-01 | The University Of Michigan | Variable frequency gas-bubble-manipulating apparatus and method |
US4865836A (en) * | 1986-01-14 | 1989-09-12 | Fluoromed Pharmaceutical, Inc. | Brominated perfluorocarbon emulsions for internal animal use for contrast enhancement and oxygen transport |
US4737323A (en) * | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
US4728578A (en) * | 1986-08-13 | 1988-03-01 | The Lubrizol Corporation | Compositions containing basic metal salts and/or non-Newtonian colloidal disperse systems and vinyl aromatic containing polymers |
US4776991A (en) * | 1986-08-29 | 1988-10-11 | The United States Of America As Represented By The Secretary Of The Navy | Scaled-up production of liposome-encapsulated hemoglobin |
US4781871A (en) * | 1986-09-18 | 1988-11-01 | Liposome Technology, Inc. | High-concentration liposome processing method |
US4893624A (en) * | 1988-06-21 | 1990-01-16 | Massachusetts Institute Of Technology | Diffuse focus ultrasound hyperthermia system |
US4957656A (en) * | 1988-09-14 | 1990-09-18 | Molecular Biosystems, Inc. | Continuous sonication method for preparing protein encapsulated microbubbles |
IL91664A (en) * | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
US5088499A (en) † | 1989-12-22 | 1992-02-18 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
IN172208B (ja) * | 1990-04-02 | 1993-05-01 | Sint Sa | |
GB9106673D0 (en) † | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
ATE243997T1 (de) * | 1991-06-18 | 2003-07-15 | Imarx Pharmaceutical Corp | Neue liposomale arzneimittelfreisetzungssysteme |
-
1991
- 1991-06-18 US US07/717,084 patent/US5228446A/en not_active Expired - Lifetime
-
1992
- 1992-03-31 JP JP50084793A patent/JP3456584B2/ja not_active Expired - Fee Related
- 1992-03-31 ES ES92912456T patent/ES2159280T5/es not_active Expired - Lifetime
- 1992-03-31 DK DK92912456T patent/DK0616508T4/da active
- 1992-03-31 DE DE69231950T patent/DE69231950T3/de not_active Expired - Lifetime
- 1992-03-31 WO PCT/US1992/002615 patent/WO1992022247A1/en active IP Right Grant
- 1992-03-31 AU AU20020/92A patent/AU667471B2/en not_active Expired
- 1992-03-31 AT AT92912456T patent/ATE203148T1/de active
- 1992-03-31 EP EP92912456A patent/EP0616508B2/en not_active Expired - Lifetime
-
2001
- 2001-10-11 GR GR20010401740T patent/GR3036877T3/el unknown
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019198461A1 (ja) * | 2018-04-10 | 2019-10-17 | 国立大学法人千葉大学 | 超音波造影及び近赤外蛍光造影の両方が可能な造影剤 |
JP2019182778A (ja) * | 2018-04-10 | 2019-10-24 | 国立大学法人千葉大学 | 超音波造影及び近赤外蛍光造影の両方が可能な造影剤 |
Also Published As
Publication number | Publication date |
---|---|
EP0616508A1 (en) | 1994-09-28 |
DE69231950T3 (de) | 2005-03-10 |
ATE203148T1 (de) | 2001-08-15 |
DK0616508T3 (da) | 2001-11-05 |
GR3036877T3 (en) | 2002-01-31 |
US5228446A (en) | 1993-07-20 |
DE69231950T2 (de) | 2002-01-17 |
JP3456584B2 (ja) | 2003-10-14 |
EP0616508A4 (en) | 1996-06-26 |
DE69231950D1 (de) | 2001-08-23 |
ES2159280T3 (es) | 2001-10-01 |
DK0616508T4 (da) | 2005-01-31 |
EP0616508B1 (en) | 2001-07-18 |
AU667471B2 (en) | 1996-03-28 |
ES2159280T5 (es) | 2005-03-16 |
AU2002092A (en) | 1993-01-12 |
WO1992022247A1 (en) | 1992-12-23 |
EP0616508B2 (en) | 2004-09-29 |
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