JP2001524983A - 新規の音響活性薬剤輸送系 - Google Patents
新規の音響活性薬剤輸送系Info
- Publication number
- JP2001524983A JP2001524983A JP54937298A JP54937298A JP2001524983A JP 2001524983 A JP2001524983 A JP 2001524983A JP 54937298 A JP54937298 A JP 54937298A JP 54937298 A JP54937298 A JP 54937298A JP 2001524983 A JP2001524983 A JP 2001524983A
- Authority
- JP
- Japan
- Prior art keywords
- gas
- oil
- vesicles
- acid
- composition
- 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.)
- Ceased
Links
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 気体もしくは気体前駆体充填マイクロスフェアを含んでなり、前記気体 もしくは気体前駆体充填マイクロスフェアが油、界面活性剤、および治療用化合 物を含むものである標的化治療剤輸送系。 2. 請求の範囲1の標的化治療剤輸送系であって、マイクロスフェアが、フ ッ素、ペルフルオロメタン、ペルフルオロエタン、ペルフルオロプロパン、ペル フルオロブタン、ペルフルオロペンタン、ペルフルオロヘキサン、六フッ化硫黄 、ヘキサフルオロプロピレン、ブロモクロロフルオロメタン、オクタフルオロプ ロパン、1,1 ジクロロ、フルオロエタン、ヘキサフルオロエタン、ヘキサフ ルオロ−2−ブチン、ペルフルオロペンタン、ペルフルオロブテン、オクタフル オロ−2−ブテン、ヘキサフルオロブタ−1,3−ジエン、オクタフルオロシク ロペンテン、ヘキサフルオロアセトン、イソプロピルアセチレン、アレン、テト ラフルオロアレン、三フッ化ホウ素、1,2−ブタジエン、1,3−ブタジエン 、1,2,3−トリクロロ−2−フロロ−1,3−ブタジエン、2−メチル−1 ,1,3−ブタジエン、ヘキサフルオロ−1,3−ブタジエン、ブタジエン、1 −フルオロ−ブタン、2−メチル−1−ブタン、デカフルオロブタン、1−ブテ ン、2−ブテン、2−メチル−1−ブテン、3−メチル−1−ブテン、ペルフル オロ−1−ブテン、ペルフルオロ−2−ブテン、4−フェニル−3−ブテン−2 −オン、2−メチル−1−ブテン−3イン、硝酸ブチル、1−ブチン、2−ブチ ン、2−クロロ−1,1,1,4,4,4−ヘキサフルオロ−ブチン、3−メチ ル−1−ブチン、ペルフルオロ−2−ブチン、2−ブロモ−ブチルアルデヒド、 硫化カルボニル、クロトンニトリル、シクロブタン、メチル −シクロブタン、オクタフルオロ−シクロブタン、ペルフルオロ−シクロブテン 、3−クロロ−シクロペンテン、シクロプロパン、1,2−ジメチル−シクロプ ロパン、1,1−ジメチル−シクロプロパン、1,2−ジメチルシクロプロパン 、エチルシクロプロパン、メチルシクロプロパン、ジアセチレン、3−エチル− 3−メチルジアジリデン、1,1,1−トリフルオロジアゾエタン、ジメチルア ミン、ヘキサフルオロ−ジメチルアミン、ジメチルエチルアミン、ビス−(ジメ チルホスフィン)アミン、2,3−ジメチル−2−ノルボルネン、ペルフルオロ ジメチルアミン、塩化ジメチルオキソニウム、1,3−ジオキソラン−2−オン 、4−メチル−1,1,1,2−テトラフルオロエタン、1,1,1−トリフル オロエタン、1,1,2,2,−テトラフルオロエタン、1,1,2−トリクロ ロ−1,2,2−トリフルオロエタン、1,1−ジクロロエタン、1,1−ジク ロロ−1,2,2,2−テトラフルオロエタン、1,2−ジフルオロエタン、1 −クロロ−1,1,2,2,2−ペンタフルオロエタン、2−クロロ−1,1− ジフルオロエタン、1−クロロ−1,1,2,2−テトラフルオロエタン、2− クロロ−1,1−ジフルオロエタン、クロロエタン、クロロペンタフルオロエタ ン、ジクロロトリフルオロエタン、フルオロエタン、ヘキサフルオロエタン、ニ トロ−ペンンタフルオロエタン、ニトロソペンタフルオロエタン、ペルフルオロ エタン、ペルフルオロエチルアミン、エチルビニルエーテル、1,1−ジクロロ −エチレン、1,1−ジクロロ−1,2−ジフルオロエチレン、1,2−ジフル オロエチレン、メタン、メタン−スルホニルクロリド−トリフルオロ、メタン− スルホニルフロリド−トリフルオロ、メタン(ペンタフルオロチオ)トリフルオ ロ、メタン−ブロモジフルオロ ニトロソ、メタン−ブロモフルオロ、メタン−ブロモクロロ−フルオロ、メタン −ブロモ−トリフルオロ、メタン−クロロジフルオロニトロ、メタン−クロロジ ニトロ、メタン−クロロフルオロ、メタン−クロロトリフルオロ、メタン−クロ ロ−ジフルオロ、メタン−ジブロモジフルオロ、メタン−ジクロロジフルオロ、 メタン−ジクロロ−フルオロ、メタン−ジフルオロ、メタン−ジフルオロ−ヨー ド、メタン−ジシラノ、メタン−フルオロ、メタン−ヨード−トリフルオロ、メ タン−ニトロ−トリフルオロ、メタン−ニトロソ−トリフルオロ、メタン−テト ラフルオロ、メタン−トリクロロフルオロ、メタン−トリフルオロ、メタンスル フェニルクロリド−トリフルオロ、2−メチルブタン、メチルエーテル、メチル イソプロピルエーテル、乳酸メチル、硝酸メチル、メチルスルフィド、メチルビ ニルエーテル、ネオン、ネオペンタン、窒素、酸化窒素、1,2,3−ノナデカ ントリカルボン酸−2−ヒドロキシトリメチルエステル、1−ノネン−3−イン 、酸素、1,4−ペンタジエン、n−ペンタン、ペンタン−ペルフルオロ、2− ペンタノン−4−アミノ−4−メチル、1−ペンテン、2−ペンテン{ジス}、 2−ペンテン{トランス}、1−ペンテン−3−ブロモ、1−ペンテン−ペルフ ルオロ、フィチン酸−テトラクロロ、ピペリジン−2,3,6−トリメチル、プ ロパン、プロパン−1,1,1,2,2,3−ヘキサフルオロ、プロパン−1, 2−エポキシ、プロパン−2,2−ジフルオロ、プロパン−2−アミノ、プロパ ン−2−クロロ、プロパン−ヘプタフルオロ−1−ニトロ、プロパン−ヘプタフ ルオロ−1−ニトロソ、プロパン−ペルフルオロ、プロペン、プロピル−1,1 ,1,2,3,3−ヘキサフルオロ−2,3−ジクロロ、プロビレン−1−クロ ロ、プロピレン−クロロ−{トラ ンス}、プロピレン−2−クロロ、プロピレン−3−フルオロ、プロピレン−ペ ルフルオロ、プロピン、プロピン−3,3,3−トリフルオロ、スチレン−3− フルオロ、六フッ化硫黄、硫黄(ジ)−デカフルオロ(S2F10)、トルエン −2,4−ジアミノ、トリフルオロアセトニトリル、過酸化トリフルオロメチル 、硫化トリフルオロメチル、六フッ化タングステン、ビニルアセチレン、ビニル エーテル、キセノン、1−ブロモフルオロブタン、およびペルフルオロエーテル 、からなる群より選択される気体前駆体を含む標的化治療剤輸送系。 3. 前記界面活性剤が、脂質、ポリマー、蛋白質、ポリペプチド、多糖、糖 、およびアクリレートからなる群より選択される、請求の範囲1の治療剤輸送系 。 4. 前記脂質が、脂肪酸;リソ脂質;ホスファチジルコリン;ジオレオイル ホスファチジルコリン;ジミリストイルホスファチジルコリン;ジペンタデカノ イルホスファチジルコリン;ジラウロイルホスファチジルコリン;ジオレオイル ホスファチジルコリン;ジパルミトイルホスファチジルコリン;ジステアロイル ホスファチジルコリン;ホスファチジルエタノールアミン;ジオレオイルホスフ ァチジルエタノールアミン;ホスファチジルセリン;ホスファチジルグリセロー ル;ホスファチジルイノシトール;スフィンゴ脂質;スフィンゴミエリン;糖脂 質;ガングリオシド GM1;ガングリオシドGM2;グルコ脂質;スルファチ ド;グリコスフィンゴリピド;ホスファチジン酸;パルミチン酸;ステアリン酸 ;アラキドン酸;オレイン酸;ポリマーを保持する脂質(例えば、ポリエチレン グリコール、キチン、ヒアルロン酸、もしくはポリビニルピロリドン);スルホ ン化されたモノ−、ジ−、オリゴ−、もしく はポリサカリド(多糖)を保持する脂質;コレステロール、硫酸コレステロール ;コレステロールヘミスクシネート;トコフェノールヘミスクシネート、エーテ ルおよびエステルが結合した脂肪酸を有する脂質、重合脂質、リン酸ジアセチル 、ステアリルアミン、カルジオリピン、長さが6〜8の炭素の短鎖脂肪酸を有す るリン脂質、不斉アシル鎖を有する合成リン脂質、6−(5−コレステン−3β −イルオキシ)−1−チオ−β−D−ガラクトピラノシド、ジガラクトシルジグ リセリド、6−(5−コレステン−3β−イルオキシ)−ヘキシル−6−アミノ −6−デオキシ−1−チオ−β−D−ガラクトピラノシド、6−(5−コレステ ン−3β−イルオキシ)ヘキシル−6−アミノ−6−デオキシル−1−チオ−α −D−ガラクトピラノシド、12−(((7’−ジエチルアミノクマリン−3− イル)カルボニル)メチルアミノ)−オクタデカン酸;N−[12−(((7’ −ジエチルアミノ−クマリン−3−イル)−カルボニル)−メチルアミノ)−オ クタデカノイル]−2−アミノパルミチン酸;コレステリル(4’−トリメチル −アンモニオ)−ブタノエート;N−スクシニルジオレイルホスファチジルエタ ノール−アミン;1,2−ジオレイル−sn−グリセロール;1,2−ジパルミ トイル−sn−3−スクシニルグリセロール;1,3−ジパルミトイル−2−ス クシニルグリセロール;1−ヘキサデシル−2−パルミトイルグリセロホスホエ タノールアミン、パルミトイルホモシステイン、および/またはそれらの組み合 わせ物;臭化ラウリルトリメチルアンモニウム、臭化セチルトリメチルアンモニ ウム、臭化ミリスチルトリメチルアンモニウム、塩化アルキルジメチルベンジル アンモニウム、臭化ベンジルジメチルドデシルアンモニウム、臭化ベンジルジメ チルヘキサデシルアンモニウム、 臭化ベンジルジメチルテトラデシルアンモニウム、臭化セチルジメチルエチルア ンモニウム、もしくは臭化セチルピリジニウム;ヨウ化ペンタフルオロオクタデ シル、臭化ペルフルオロオクチル、ペルフルオロデカリン、ペルフルオロドデカ リン、ヨウ化ペルフルオロオクチル、ペルフルオロトリプロピルアミン、および ペルフルオロトリブチルアミン、ならびにさらには共有結合により結合したポリ マーを保持する脂質、からなる群より選択される、請求の範囲3の治療剤輸送系 。 5. 前記蛋白質が、コラーゲン、フィブリン、およびアルブミンからなる群 より選択される、請求の範囲3の組成物。 6. 前記ポリペプチドが、ポリグルタミン酸、ポリリシン、ポリホスファゼ ン、ポリビニルアルコール、ポリエチレングリコール、ポリプロピレングリコー ル、およびコポリマーからなる群より選択される、請求の範囲3の組成物。 7. 前記多糖が、スターチ、HETA−スターチ、アルギン酸、ヒアルロン 酸、セルロース、およびサッカリドからなる群より選択される、請求の範囲3の 組成物。 8. 前記セルロースがメチルセルロースである、請求の範囲7の組成物。 9. 前記サッカリドがデキストランである、請求の範囲7の組成物。 10. 前記糖が、グルコースおよびガラクトースからなる群より選択される、 請求の範囲3の組成物。 11. 前記ポリマーが、合成ポリマー、天然ポリマー、および半合成ポリマー からなる、請求の範囲3の組成物。 12. 前記合成ポリマーがポリ乳酸である、請求の範囲11の組成物。 13. 前記コポリマーが、ポリラトシデコグリコリドおよびポリエチレン−ポ リプロピレングリコールからなる群より選択される、請求の範囲6の組成物。 14. 前記アクリレートがメタクリレートである、請求の範囲3の組成物。 15. 前記メタクリレートがメチルメタクリレートである、請求の範囲14の 組成物。 16. 前記油が、シリコン油、タラ肝油、鉱油、植物油、フッ素化されたトリ グリセリドを含む油、生物適合性の飽和脂肪酸、生物適合性不飽和脂肪酸、およ び生物適合性の部分的に水素化された脂肪酸、シリコンベースの油、ならびに合 成油からなる群から選択される、請求の範囲1の組成物。 17. 前記治療剤が前記マイクロスフェアの表面に結合する、請求の範囲1の 組成物。 18. 前記治療剤が前記マイクロスフェア内に被包される、請求の範囲1の組 成物。 19. 前記マイクロスフェアが、凍結乾燥マイクロスフェア、噴霧乾燥マイク ロスフェア、ボールミルマイクロスフェア、撹拌マイクロスフェア、およびそれ らのいずれかの組み合わせ物からなる群より選択される、請求の範囲1の組成物 。 20. 前記植物油が、ピーナッツ油、カノーラ油、オリーブ油、ベニバナ油、 コーン油、およびマゾーラ油からなる群より選択される、請求の範囲16の組成 物。 21. 前記シリコンベースの油が、ビニル末端をもつ、ヒドリド末端 をもつ、シラノール末端をもつ、アミノ末端をもつ、エポキシ末端をもつ、カル ビノール末端をもつ液体、メルカプト誘導化させたシリコン液、飽和シリコン油 、不飽和シリコン油、アリールアルキル飽和シリコン油からなる群より選択され る、請求の範囲16の組成物。 22. 前記合成油が、C12〜C24脂肪酸の飽和鎖、およびC12〜C24脂肪酸の 不飽和鎖からなる群より選択される、請求の範囲16の組成物。 23. 前記合成油が、オレイン酸のグリセロールトリグリセリドエステルから なる群より選択される、請求の範囲22の組成物。 24. 更に標的化用リガンドを含む、請求の範囲1の標的化治療剤輸送系。 25. 気体もしくは気体前駆体充填マイクロスフェアを含む標的化治療剤輸送 系を製造する、気体前駆体の存在下で油および界面活性剤を含む溶液を処理する 段階、および前記マイクロスフェアに治療学的組成物を添加する段階を含み、前 記処理が調節下での撹拌、調節下での乾燥、およびその組み合わせ物からなる群 より選択される方法。 26. 前記方法が、気体前駆体の活性化温度で気体前駆体を用いて実施される 、請求の範囲25に従う方法。 27. 調節下での撹拌が、ボールミル、震盪、ボルテックルミキサーでの撹拌 、およびそれらの組み合わせ物からなる群より選択される、請求の範囲25に従 う方法。 28. 調節下での乾燥が、凍結乾燥、噴霧乾燥、およびそれらの組み合わせ物 からなる群より選択される、請求の範囲25に従う方法。 29. 更に前記脂質水溶液の濾過段階および熱滅菌段階を含む、請求の範囲2 5に従う方法。 30. (i)患者に、油、界面活性剤、気体もしくは気体前駆体、および治療 剤を含む標的化治療剤輸送系を投与すること; (ii)標的化治療剤輸送系を、その領域の標的化治療剤輸送系の存在 を決定するためのエネルギーを用いてモニターすること;ならびに (iii)その領域内で標的化治療剤輸送系から治療剤を放出させるこ と: を含む、標的化治療剤輸送系の制御下輸送のための方法。 31. 黄斑変性症の治療の際の使用のための、前記治療剤がα−トコフェロー ルおよびレチン酸を含み、前記油が大豆油であり、前記界面活性剤が82モルパ ーセントのジパルミトイルホスファチジルコリン、10モルパーセントのジパル ミトイルホスファチジン酸、および8モルパーセントのジパルミトイルホスファ チジルエタノールアミン−ポリエチレングリコール5000を含み、そして前記 気体前駆体がペルフルオロブタンである、請求の範囲30の方法。 32. 網膜芽細胞腫を治療する際の使用のための、前記治療剤がタキソールお よびレチン酸を含み、前記油が大豆油であり、前記界面活性剤が82モルパーセ ントのジパルミトイルホスファチジルコリン、10モルパーセントのジパルミト イルホスファチジン酸、および8モルパーセントのジパルミトイルホスファチジ ルエタノールアミン−ポリエチレングリコール5000を含み、そして前記気体 前駆体がペルフルオロブタンである、請求の範囲30の方法。 33. 前記治療剤がアンフォテリシン−Bであり、前記油が大豆油であり、前 記界面活性剤が82モルパーセントのジパルミトイルホスファ チジルコリン、10モルパーセントのジパルミトイルホスファチジン酸、8モル パーセントのジパルミトイルホスファチジルエタノールアミン−ポリエチレング リコール5000、およびプルロニック(Pluronic)F−68を含み、 そして前記気体前駆体がペルフルオロブタンである、請求の範囲30の方法。 34. 真菌性眼炎を治療するために用いられる、請求の範囲33の方法。 35. 色素性網膜症を治療するための、前記治療剤がベンダゾックであり、前 記油が大豆油であり、前記界面活性剤が82モルパーセントのジパルミトイルホ スファチジルコリン、10モルパーセントのジパルミトイルホスファチジン酸、 8モルパーセントのジパルミトイルホスファチジルエタノールアミン−ポリエチ レングリコール5000、およびプルロニック(Pluronic)F−68を 含み、そして前記気体前駆体がペルフルオロブタンである、請求の範囲30の方 法。 36. 良性前立腺肥大を治療するための、前記治療剤がドキサゾシンであり、 前記油が大豆油であり、前記界面活性剤が82モルパーセントのジパルミトイル ホスファチジルコリン、10モルパーセントのジパルミトイルホスファチジン酸 、8モルパーセントのジパルミトイルホスファチジルエタノールアミン−ポリエ チレングリコール5000、およびプルロニック(Pluronic)F−68 を含み、そして前記気体前駆体がペルフルオロブタンである、請求の範囲30の 方法。 37. 前記治療剤がα−トコフェロールであり、前記界面活性剤がCF3(C F2)8(CH2)6COOHを含み、前記油がカノーラ油であり、そして前記気体 前駆体がペルフルオロブタンである、請求の範囲30の 方法。 38. 前記治療剤が染料であり、前記油が大豆油であり、前記界面活性剤が8 2モルパーセントのジパルミトイルホスファチジルコリン、8モルパーセントの ジパルミトイルホスファチジルエタノールアミン−ポリエチレングリコール50 00、および10モルパーセントのジパルミトイルホスファチジン酸を含み、前 記気体前駆体がペルフルオロプロパンである、請求の範囲30の方法。 39. 前記治療剤がデキサメサゾンであり、前記界面活性剤が82モルパーセ ントのジパルミトイルホスファチジルコリン、8モルパーセントのジパルミトイ ルホスファチジルエタノールアミン−ポリエチレングリコール5000、および 10モルパーセントのジパルミトイルホスファチジン酸を含み、前記気体前駆体 がペルフルオロブタンおよび窒素である、請求の範囲30の方法。 40. 前記治療剤がアンホテリシンであり、前記界面活性剤が82モルパーセ ントのジパルミトイルホスファチジルコリン、8モルパーセントのジパルミトイ ルホスファチジルエタノールアミン−ポリエチレングリコール5000、および 10モルパーセントのジパルミトイルホスファチジン酸を含み、前記気体前駆体 がペルフルオロブタンおよび窒素から選択される、請求の範囲30の方法。 41. 前記治療剤が染料を含む、請求の範囲25の組成物。 42. 前記染料が、蛍光染料および比色分析用染料からなる群より選択される 、請求の範囲41の組成物。 43. 前立腺癌もしくは良性前立腺肥大を治療するための、前記治療剤が、テ ストステロン、メチルテストステロン、フルオキシメステロン、 フィナステリド、および5aレダクターゼ酵素阻害剤からなる群より選択される 、請求の範囲30の方法。 44. 前記染料が、スダンブラック、フルオレセイン、R−フィコエリスリン (R−Phycoerythrin)、テキサスレッド、BODIPYFL、オ レゴングリーン、ローダミンレッド−X、テトラメチルローダミン、BODIP Y TMR、BODIPY−TR、YOYO−1、DAPI、インド−1(In do−1)、カスケードブルー(Cascade blue)、フラ−2,アミ ノメチルクマリン、FM1−43、NBD、カルボシ−SNARF、ルシフェル イエロー、ダンシル+R−NH2、ヨウ化プロピジウム、メチレンブルー、ブロ モクレゾールブルー、アクリジンオレンジ、ブロモフェノールブルー、7−アミ ノ−アクチノマイシンD、アロフィコシアニン、9−アジドアクリジン、ベンゾ キサンテン−イエロー、ビスベンジジンH33258蛍光色素、3HCl、5− カルボキシフルオレッセインジアセテート、4−クロロ−1−ナフトール、クロ モマイシン−A3、DTAF、DTNB、臭化エチジウム、フルオレセイン−5 −マレイミドジアセテート、ミスラマイシンA、ローダミン123、SBFI、 SIST、テトラメチルベンジジン、テトラメチルプルプレート、チアゾリルブ ルー、およびTRITCからなる群より選択される、請求の範囲41の方法。 45. 前記フルオレセインがフルオレセインイソチオシアネートである、請求 の範囲44の方法。 46. 前記フルオレセインイソチオシアネートが、フルオレセインイソチオシ アネートアルブミン、フルオレセインイソチオシアネート抗体複合体、フルオレ セインイソチオシアネートα−ブンガロトキシン、フ ルオレセインイソチオシアネート−カゼイン、フルオレセインイソチオシアネー ト−デキストラン、フルオレセインイソチオシアネート−インスリン、フルオレ セインイソチオシアネート−レクチン(Lectin)、フルオレセインイソチ オシアネート−ペルオキシダーゼ、およびフルオレセインイソチオシアネート− プロテインAからなる群より選択される、請求の範囲44の方法。
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Also Published As
Publication number | Publication date |
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US20020159952A1 (en) | 2002-10-31 |
AR012691A1 (es) | 2000-11-08 |
EP0981333A4 (en) | 2002-04-24 |
EP0981333A1 (en) | 2000-03-01 |
AU7796198A (en) | 1998-12-08 |
US6416740B1 (en) | 2002-07-09 |
JP2010280678A (ja) | 2010-12-16 |
WO1998051284A1 (en) | 1998-11-19 |
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