JP5097540B2 - 腸管吸収用抗腫瘍剤 - Google Patents
腸管吸収用抗腫瘍剤 Download PDFInfo
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- JP5097540B2 JP5097540B2 JP2007512928A JP2007512928A JP5097540B2 JP 5097540 B2 JP5097540 B2 JP 5097540B2 JP 2007512928 A JP2007512928 A JP 2007512928A JP 2007512928 A JP2007512928 A JP 2007512928A JP 5097540 B2 JP5097540 B2 JP 5097540B2
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- antitumor
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- hydroxyapatite
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Description
癌細胞の代謝を阻害することによって、がん細胞の機能に障害を与えて癌細胞の増殖を抑える代謝拮抗剤;
自然界の微生物から得られた抗生物質の中で癌の細胞膜を破壊したり、DNAを分解したり、合成を阻止する等の抗ガン性のある抗腫瘍性抗生物質;
植物から得られた植物アルカロイドにより細胞分裂を停止させ細胞障害を与える植物製剤;
癌細胞にホルモンが結合する部分に反対の作用をするホルモン剤またはホルモン拮抗剤が先に結合して、抗癌作用を示すホルモン製剤;
免疫系を活性化することを目的とした免疫賦活剤;
癌に対する免疫応答の調整、増強を目的としたサイトカインなどの免疫治療剤;
DNAと結合することにより癌細胞の細胞分裂を阻害する白金製剤;
その他、キナーゼ阻害剤、ヒスタミンAの誘導体、放線菌のアミノペプチダーゼ、アルキル化剤や代謝拮抗剤に似た作用があるマンニトール誘導体、血中のL−アスパラギンを分解してアスパラギン要求性腫瘍細胞を栄養欠乏状態にする酵素製剤、ビスジオキソピペラジン誘導体、膀胱腫瘍再発抑制剤のアセグラトンなどの前記に分類されない抗腫瘍剤などが開発されている。
〔2〕 前記ハイドロキシアパタイトの最大粒径が10μm以下であることを特徴とする〔1〕記載の腸管吸収用抗腫瘍剤。
〔3〕 ハイドロキシアパタイトの最大粒径が0.5μm以下であることを特徴とする〔1〕または〔2〕記載の腸管吸収用抗腫瘍剤。
〔4〕 ハイドロキシアパタイトの最大粒径が0.1μm以下であることを特徴とする〔1〕〜〔3〕のいずれかに記載の腸管吸収用抗腫瘍剤。
〔5〕 ハイドロキシアパタイトの配合量が注射用抗腫瘍成分に対して0.5〜5000重量%であることを特徴とする〔1〕〜〔4〕のいずれかに記載の腸管吸収用抗腫瘍剤。
〔6〕 前記注射用抗腫瘍成分が、白金製剤、サイトカイン、アルキル化剤、代謝拮抗剤、抗腫瘍性抗生物質、植物製剤、免疫治療剤、キナーゼ阻害剤、酵素製剤、ヒスタミンA誘導体、アミノペプチダーゼ、マンニトール誘導体、ビスジオキソピペラジン誘導体、膀胱腫瘍再発抑制剤または癌疼痛治療剤である〔1〕〜〔5〕のいずれかに記載の腸管吸収用抗腫瘍剤。
〔7〕 前記白金製剤がシスプラチン、カルボプラチン、ネダプラチン、前記サイトカインがインターフェロン、前記アルキル化剤がラニムスチン、塩酸ニムスチン、イホスファミド、ダカルバジン、チオテバ、前記代謝拮抗剤が塩酸ゲムシタビン、シタラビン、エノシタビン、リン酸フルダラビン、レボホリナートカルシウム、硫酸ビンクリスチン、硫酸ビンブラスチン、前記抗腫瘍性抗生物質が硫酸ペプロマイシン、塩酸ピラルビシン、ジノスタチン・スチマラマー、塩酸イダルビシン、マイトマイシンC、塩酸ブレオマイシン、塩酸ドキソルビシン、塩酸ダウノルビシン、塩酸エピルビシン、前記植物製剤が硫酸ビンデシン、酒石酸ビノレルビン、塩酸イリノテカン、塩酸ノギテカン、ドセタキセル水和物、パクリタキセルからなる群から選ばれる少なくとも1種であることを特徴とする〔6〕記載の腸管吸収用抗腫瘍剤。
〔8〕前記ハイドロキシアパタイトが、アモルファスハイドロキシアパタイトである、〔1〕〜〔7〕のいずれかに記載の腸管吸収用抗腫瘍剤。
〔9〕腸管吸収用抗腫瘍剤を製造するための、注射用抗腫瘍成分が担持されたハイドロキシアパタイト粒子の使用。
〔10〕腫瘍の治療または予防が必要な患者に、〔1〕に記載された腸管吸収用抗腫瘍剤の有効量を投与する腫瘍の治療方法。
例えば、前記白金製剤がシスプラチン、カルボプラチン、ネダプラチン、前記サイトカインがインターフェロン、前記アルキル化剤がラニムスチン、塩酸ニムスチン、イホスファミド、ダカルバジン、チオテバ、前記代謝拮抗剤が塩酸ゲムシタビン、シタラビン、エノシタビン、リン酸フルダラビン、レボホリナートカルシウム、硫酸ビンクリスチン、硫酸ビンブラスチン、抗腫瘍性抗生物質が硫酸ペプロマイシン、塩酸ピラルビシン、ジノスタチン・スチマラマー、塩酸イダルビシン、マイトマイシンC、塩酸ブレオマイシン、塩酸ドキソルビシン、塩酸ダウノルビシン、塩酸エピルビシン、前記植物製剤が硫酸ビンデシン、酒石酸ビノレルビン、塩酸イリノテカン、塩酸ノギテカン、ドセタキセル水和物、パクリタキセル。
抗腫瘍成分およびハイドロキシアパタイトとして、好ましくは前記薬剤成分およびハイドロキシアパタイトを用いることができる。
なお本明細書において引用された全ての先行技術文献は、参照として本明細書に組み入れられる。
アモルファスハイドロキシアパタイトの製造
攪拌下の水酸化カルシウム懸濁液中に、30重量%濃度のリン酸水溶液を、PH10になるまで滴下し、生成したゲル状物質を室温で1日間放置して熟成した。その後、ゲル状物質をガラスフィルターで濾過し、残った物質を100℃の空気中で乾燥を行なうことにより、図1下図の回折パターンを有するアモルファスハイドロキシアパタイトを得た。
結晶性ハイドロキシアパタイトの製造
調製例1で得られたアモルファスハイドロキシアパタイトの一部を空気中にて800℃、2時間焼成して、図1上図の回折パターンを有する結晶性ハイドロキシアパタイトを得た。
[実施例1−1]
シスプラチンをN,N−ジメチルホルムアミドに溶解し、その溶液中に、ジェットミル(Co-Jetシステムα-mkII 株式会社セイシン企業製)で最大粒径を10μm以下に粉砕したアモルファスハイドロキシアパタイトを所定量添加して、減圧下、室温で一晩撹拌した。この溶液を陰圧下で乾燥して、最大粒径が10μm以下(平均粒径、約5μm)の、溶媒を除去したハイドロキシアパタイト添加・粉砕シスプラチン抗腫瘍紛体を得た(実施例1−1)。
最大粒径を10μm以下に粉砕したアモルファスハイドロキシアパタイトの代わりに、ジェットミルで最大粒径を5μm以下に粉砕したアモルファスハイドロキシアパタイトを用いて、上記と同様の方法で、最大粒径が5μm以下(平均粒径、約2μm)の、溶媒を除去したハイドロキシアパタイト添加・粉砕シスプラチン抗腫瘍紛体を得た(実施例1−2)。
蒸留水にアモルファスハイドロキシアパタイトを2重量%添加して、ダイノーミル(ECM-PILOT Willy A. Baechofen AG Machinenfabrik Basel社製)で粉砕を行った。粉砕は、冷却用循環ポンプを使用して、5℃以下の温度で行なった。粒子の大きさを測定して最大粒径が0.5μm以下になったところで一部溶液を取り出し、この溶液を陰圧下で乾燥して、最大粒径が0.5μm以下のアモルファスハイドロキシアパタイト微粒子を得た。更に残りの溶液を粉砕して、最大粒径が0.1μm以下になったところで粉砕を終了し、この溶液を陰圧下で乾燥して、最大粒径が0.1μm以下のアモルファスハイドロキシアパタイト微粒子を得た。
上記と同様に、ジェットミルを用いて最大粒径5μm以下に粉砕した結晶性ハイドロキシアパタイトを、またダイノーミルを用いて最大粒径0.5μm以下に粉砕した結晶性ハイドロキシアパタイトを作成し、上記のアモルファスハイドロキシアパタイトをこれらの結晶性ハイドロキシアパタイトに変えて、抗腫瘍粉体を作成し、最大粒径が5μm以下(平均粒径、約2μm)と、0.5μm以下(平均粒径、約0.2μm)の結晶性ハイドロキシアパタイト添加・粉砕シズプラチン抗腫瘍粉体を得た(実施例1−5、実施例1−6)。
更に上記と同様の方法で、アモルファスハイドロキシアパタイトを第三リン酸カルシウムに変えて、ダイノーミルを用いて最大粒径0.5μm以下の第三リン酸カルシウム微粒子を作成し、上記と同様の方法で、最大粒径が0.5μm以下(平均粒径、約0.2μm)の第三リン酸カルシウム添加・粉砕シズプラチン抗腫瘍粉体を得た(参考例1)。
アモルファスハイドロキシアパタイトを2重量%添加した蒸留水中に、インターフェロンβ、イホスファミド、塩酸ブレオマイシン、硫酸ビンクリスチンの各種抗腫瘍剤を、それぞれ所定量添加して減圧下で撹拌した。
これらそれぞれの抗腫瘍溶液をダイノーミルで、冷却用循環ポンプを使用して、5℃以下の温度で粉砕を行ない、粉砕後これらの各種抗腫瘍溶液を乾燥して、最大粒径が0.4〜0.5μm以下(平均粒径、約0.2μm)のハイドロキシアパタイト添加・粉砕各種抗腫瘍紛体を得た(実施例1−7〜実施例1−10)。
ハイドロキシアパタイト添加量は、抗腫瘍剤に対するハイドロキシアパタイトの割合(重量%)を示す。
[試験例1−1−1〜1−1−4、試験例1−2−1〜1−2−4、試験例1−4−1〜1−4−6、試験例1−5−1〜1−5−4]
試験例1−1−1〜1−1−4、試験例1−2−1〜1−2−4、試験例1−4−1〜1−4−6、及び試験例1−5−1〜1−5−4の試料を、Sprague-Dawley系の雄(7週齢)に経口投与した。投与は、ラットに充分に摂餌させて、ラット用経口胃ゾンデを用いて、胃内に強制経口投与した。
試験例1−3−1〜1−3−4、試験例1−6−1〜1−6−4、及び参考試験例1−1〜1−4の試料を、Sprague-Dawley系の雄(7週齢)に経口投与した。投与は、抗腫瘍剤がラットの胃酸で溶解する前に胃を通過させる為に、ラットを16時間絶食させ空腹状態にして、ラット用経口胃ゾンデを用いて、胃内に強制経口投与した。
比較として、ラットを16時間絶食後、上記と同様の方法で、シスプラチンを同投与量で経口投与を行った(比較試験例1−1)。更に比較として、シスプラチン2mg/Kgの血管内投与を行った(比較試験例1−2)。
[試験例4−7〜試験例4−10、比較試験例4−1〜4−4]
実施例1−7−1、実施例1−8−2、実施例1−9−3、実施例1−10−4の試料を、Sprague-Dawley系の雄(7週齢)に経口投与した。投与は、ラットを16時間絶食後、ラット用経口胃ゾンデを用いて胃内に強制経口投与した。
血漿中の各種抗腫瘍剤濃度は、ガスクロマトグラフおよび液体クロマトグラフを用いて測定を行い、その結果を表3に示した。
Claims (9)
- アモルファスハイドロキシアパタイトの粒子に注射用抗腫瘍成分が担持された、腸管吸収用抗腫瘍剤であって、
該腸管吸収用抗腫瘍剤は経口投与用であり;
該アモルファスハイドロキシアパタイトの最大粒径が0.5μm以下である、腸管吸収用抗腫瘍剤。 - アモルファスハイドロキシアパタイトの最大粒径が0.5μm以下であり、平均粒径が0.3μm以下である、請求項1に記載の腸管吸収用抗腫瘍剤。
- アモルファスハイドロキシアパタイトの平均粒径が0.01μm以上である、請求項1または2に記載の腸管吸収用抗腫瘍剤。
- アモルファスハイドロキシアパタイトの最大粒径が0.1μm以下であることを特徴とする請求項1〜3のいずれかに記載の腸管吸収用抗腫瘍剤。
- アモルファスハイドロキシアパタイトの配合量が注射用抗腫瘍成分に対して0.5〜5000重量%であることを特徴とする請求項1〜4のいずれかに記載の腸管吸収用抗腫瘍剤。
- 前記注射用抗腫瘍成分が、白金製剤、サイトカイン、アルキル化剤、代謝拮抗剤、抗腫瘍性抗生物質、植物製剤、免疫治療剤、キナーゼ阻害剤、酵素製剤、ヒスタミンA誘導体、アミノペプチダーゼ、マンニトール誘導体、ビスジオキソピペラジン誘導体、膀胱腫瘍再発抑制剤または癌疼痛治療剤である請求項1〜5のいずれかに記載の腸管吸収用抗腫瘍剤。
- 前記白金製剤がシスプラチン、カルボプラチン、ネダプラチン、前記サイトカインがインターフェロン、前記アルキル化剤がラニムスチン、塩酸ニムスチン、イホスファミド、ダカルバジン、チオテバ、前記代謝拮抗剤が塩酸ゲムシタビン、シタラビン、エノシタビン、リン酸フルダラビン、レボホリナートカルシウム、硫酸ビンクリスチン、硫酸ビンブラスチン、前記抗腫瘍性抗生物質が硫酸ペプロマイシン、塩酸ピラルビシン、ジノスタチン・スチマラマー、塩酸イダルビシン、マイトマイシンC、塩酸ブレオマイシン、塩酸ドキソルビシン、塩酸ダウノルビシン、塩酸エピルビシン、前記植物製剤が硫酸ビンデシン、酒石酸ビノレルビン、塩酸イリノテカン、塩酸ノギテカン、ドセタキセル水和物、パクリタキセルからなる群から選ばれる少なくとも1種であることを特徴とする請求項6記載の腸管吸収用抗腫瘍剤。
- 前記注射用抗腫瘍成分が、シスプラチン、インターフェロンβ、イホスファミド、塩酸ブレオマイシンおよび硫酸ビンクリスチンからなる群から選ばれる少なくとも1種である、請求項1〜7のいずれかに記載の腸管吸収用抗腫瘍剤。
- 腸管吸収用抗腫瘍剤を製造するための、注射用抗腫瘍成分が担持されたアモルファスハイドロキシアパタイト粒子の使用であって、
該腸管吸収用抗腫瘍剤は経口投与用であり;
該アモルファスハイドロキシアパタイトの最大粒径が0.5μm以下である、使用。
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Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04112832A (ja) * | 1990-08-31 | 1992-04-14 | Sangi Co Ltd | 抗腫瘍剤 |
JPH09166697A (ja) * | 1995-12-15 | 1997-06-24 | Noboru Harada | 小線源及びそれを含有する医薬用組成物 |
JPH09165328A (ja) * | 1995-12-15 | 1997-06-24 | Noboru Harada | 小球体及びそれを含有する医薬用組成物 |
WO1998009645A1 (fr) * | 1996-09-04 | 1998-03-12 | Dott Research Laboratory | Compositions medicamenteuses contenant des peptides, destinees a l'administration orale |
JPH115751A (ja) * | 1997-04-24 | 1999-01-12 | Takeda Chem Ind Ltd | アパタイト被覆固形組成物およびその製造法 |
JP2001524937A (ja) * | 1996-10-16 | 2001-12-04 | エテックス コーポレイション | 生体セラミック組成物 |
JP2003512336A (ja) * | 1999-10-18 | 2003-04-02 | ファークス インコーポレーテッド | 磁気標的化キャリア |
US6767550B1 (en) * | 2000-06-30 | 2004-07-27 | Berkeley Advanced Biomaterials, Inc. | Hydroxyapatite based drug delivery implant for cancer treatment |
WO2004112751A1 (ja) * | 2003-06-18 | 2004-12-29 | Ltt Bio-Pharma Co., Ltd. | 薬物含有徐放性微粒子、その製造法、及びそれを含有する製剤 |
WO2005074991A1 (ja) * | 2004-02-09 | 2005-08-18 | Kabushiki Kaisha Sangi | 抗腫瘍剤 |
Family Cites Families (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0692288B2 (ja) | 1986-07-22 | 1994-11-16 | 株式会社資生堂 | 皮膚外用剤 |
JPS63107938A (ja) | 1986-10-25 | 1988-05-12 | Sangi:Kk | 皮膚疾患治療剤 |
JP2640101B2 (ja) | 1987-01-30 | 1997-08-13 | 株式会社 資生堂 | 皮膚外用剤 |
JPS63255231A (ja) | 1987-04-14 | 1988-10-21 | Arusu Japan:Kk | 塞栓剤 |
JPH02200628A (ja) | 1989-01-31 | 1990-08-08 | Central Glass Co Ltd | 徐放性抗腫瘍剤およびその製造方法 |
US5443832A (en) * | 1990-04-16 | 1995-08-22 | Institut Swisse De Recherches Experimentales Sur Le Cancer | Hydroxyapatite-antigen conjugates and methods for generating a poly-Ig immune response |
JPH0474125A (ja) | 1990-07-16 | 1992-03-09 | Sangi Co Ltd | 温熱療法用加温補助材 |
JPH05178762A (ja) | 1991-07-02 | 1993-07-20 | Sekisui Chem Co Ltd | 経皮・経粘膜吸収製剤 |
JPH05238956A (ja) | 1991-07-09 | 1993-09-17 | Yoshiyuki Koyama | 薬物担体及びそれを用いた複合体 |
JPH05255095A (ja) | 1992-03-13 | 1993-10-05 | Advance Co Ltd | 血管内投与剤 |
ES2160582T3 (es) | 1992-04-03 | 2001-11-16 | Nippon Kayaku Kk | Capsula dura de ocfosfato de citarabina. |
JP2676305B2 (ja) | 1992-04-03 | 1997-11-12 | 日本化薬株式会社 | シタラビンオクホスファート硬カプセル剤 |
JP3471840B2 (ja) | 1993-03-04 | 2003-12-02 | 日本ワイスレダリー株式会社 | 外用剤 |
JPH072689A (ja) | 1993-04-19 | 1995-01-06 | Advanced Sukin Res Kenkyusho:Kk | 難吸収性物質を含有するマイクロエマルション製剤 |
JPH06329557A (ja) | 1993-05-21 | 1994-11-29 | Meiji Milk Prod Co Ltd | 生理活性物質吸着用担体 |
JPH07101864A (ja) | 1993-10-01 | 1995-04-18 | Sekisui Chem Co Ltd | 経皮吸収貼付剤 |
JPH07165613A (ja) | 1993-10-19 | 1995-06-27 | Dot:Kk | 経鼻吸収薬物用キャリヤおよび生理活性ペプチド組成物 |
JP3414539B2 (ja) | 1994-05-11 | 2003-06-09 | 有限会社ドット | 経鼻吸収用組成物 |
JPH0820594A (ja) | 1994-07-06 | 1996-01-23 | Tanaka Kikinzoku Kogyo Kk | 抗腫瘍性シクロアルカンアミン誘導体白金(iv)錯体 |
JPH0827174A (ja) | 1994-07-15 | 1996-01-30 | Tanaka Kikinzoku Kogyo Kk | 抗腫瘍性シクロヘキサンジアミン誘導体白金(iv)錯体 |
JP3115774B2 (ja) | 1994-10-17 | 2000-12-11 | 田中貴金属工業株式会社 | 抗腫瘍性白金(iv)錯体 |
US6541037B1 (en) * | 1995-05-19 | 2003-04-01 | Etex Corporation | Delivery vehicle |
JP3417744B2 (ja) | 1995-10-24 | 2003-06-16 | カネボウ株式会社 | 経皮吸収促進剤および皮膚外用剤 |
JP3770666B2 (ja) | 1996-09-20 | 2006-04-26 | 株式会社ティ・ティ・エス技術研究所 | 経粘膜吸収製剤用組成物 |
CN1086917C (zh) | 1996-10-31 | 2002-07-03 | 青木秀希 | 口香糖组合物及其制造方法 |
JPH10251285A (ja) | 1997-03-14 | 1998-09-22 | Ss Pharmaceut Co Ltd | 白金(iv)錯体及びこれを含有する医薬 |
US6344209B1 (en) * | 1997-04-24 | 2002-02-05 | Takeda Chemical Industries, Ltd. | Apatite-coated solid composition |
JPH1180031A (ja) | 1997-07-14 | 1999-03-23 | Sekisui Chem Co Ltd | 外用剤及び経皮又は経粘膜吸収性を増進する方法 |
JP2001048865A (ja) | 1999-06-03 | 2001-02-20 | Takeda Chem Ind Ltd | 経鼻剤 |
US6881420B2 (en) * | 2000-06-23 | 2005-04-19 | Teva Pharmaceutical Industries Ltd. | Compositions and dosage forms for gastric delivery of irinotecan and methods of treatment that use it to inhibit cancer cell proliferation |
WO2002041844A2 (en) | 2000-10-20 | 2002-05-30 | Etex Corporation | Chemotherapeutic composition using nanocrystalline calcium phosphate paste |
HUP0400683A2 (hu) * | 2000-12-11 | 2004-06-28 | Takeda Chemical Industries, Ltd. | HER2 inhibitort tartalmazó fokozott felszívódású gyógyászati készítmény |
ATE307571T1 (de) | 2001-02-27 | 2005-11-15 | Pharmazeutische formulierung enthaltend bicalutamid | |
JP2003250454A (ja) | 2002-02-27 | 2003-09-09 | Lion Corp | 酵素配合咀嚼用組成物包装体 |
AU2003218271A1 (en) * | 2002-04-18 | 2003-11-03 | Carnegie Mellon University | Method of manufacturing hydroxyapatite and uses therefor in delivery of nucleic acids |
JP2004075662A (ja) | 2002-06-20 | 2004-03-11 | Mukku:Kk | 徐放性組成物、その製造方法およびその製剤 |
US20060216299A1 (en) * | 2002-10-30 | 2006-09-28 | Rigel Pharmaceuticals, Inc. | Cell cycle targets and peptides |
JP2004307398A (ja) | 2003-04-07 | 2004-11-04 | National Institute For Materials Science | 薬物封入多層構造微粒子 |
CA2522152A1 (en) | 2004-10-07 | 2006-04-07 | Kabushiki Kaisha Sangi | Transdermal and transmucosal preparations |
JP4889978B2 (ja) | 2005-08-12 | 2012-03-07 | 株式会社サンギ | 経口摂取用組成物 |
-
2006
- 2006-04-05 EP EP06731137.3A patent/EP1872798B1/en not_active Expired - Fee Related
- 2006-04-05 JP JP2007512928A patent/JP5097540B2/ja not_active Expired - Fee Related
- 2006-04-05 US US11/887,710 patent/US8293274B2/en active Active
- 2006-04-05 WO PCT/JP2006/307189 patent/WO2006109635A1/ja active Application Filing
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04112832A (ja) * | 1990-08-31 | 1992-04-14 | Sangi Co Ltd | 抗腫瘍剤 |
JPH09166697A (ja) * | 1995-12-15 | 1997-06-24 | Noboru Harada | 小線源及びそれを含有する医薬用組成物 |
JPH09165328A (ja) * | 1995-12-15 | 1997-06-24 | Noboru Harada | 小球体及びそれを含有する医薬用組成物 |
WO1998009645A1 (fr) * | 1996-09-04 | 1998-03-12 | Dott Research Laboratory | Compositions medicamenteuses contenant des peptides, destinees a l'administration orale |
JP2001524937A (ja) * | 1996-10-16 | 2001-12-04 | エテックス コーポレイション | 生体セラミック組成物 |
JPH115751A (ja) * | 1997-04-24 | 1999-01-12 | Takeda Chem Ind Ltd | アパタイト被覆固形組成物およびその製造法 |
JP2003512336A (ja) * | 1999-10-18 | 2003-04-02 | ファークス インコーポレーテッド | 磁気標的化キャリア |
US6767550B1 (en) * | 2000-06-30 | 2004-07-27 | Berkeley Advanced Biomaterials, Inc. | Hydroxyapatite based drug delivery implant for cancer treatment |
WO2004112751A1 (ja) * | 2003-06-18 | 2004-12-29 | Ltt Bio-Pharma Co., Ltd. | 薬物含有徐放性微粒子、その製造法、及びそれを含有する製剤 |
WO2005074991A1 (ja) * | 2004-02-09 | 2005-08-18 | Kabushiki Kaisha Sangi | 抗腫瘍剤 |
Also Published As
Publication number | Publication date |
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EP1872798A4 (en) | 2008-12-03 |
US8293274B2 (en) | 2012-10-23 |
WO2006109635A1 (ja) | 2006-10-19 |
EP1872798A1 (en) | 2008-01-02 |
EP1872798B1 (en) | 2013-06-05 |
JPWO2006109635A1 (ja) | 2008-11-06 |
US20090136577A1 (en) | 2009-05-28 |
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