JPWO2009157279A1 - シスプラチン配位化合物の液体組成物 - Google Patents
シスプラチン配位化合物の液体組成物 Download PDFInfo
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- A—HUMAN NECESSITIES
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6907—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a microemulsion, nanoemulsion or micelle
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
- C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
- C08G69/10—Alpha-amino-carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/40—Polyamides containing oxygen in the form of ether groups
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/0233—Polyamines derived from (poly)oxazolines, (poly)oxazines or having pendant acyl groups
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/0091—Complexes with metal-heteroatom-bonds
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
このような問題点を解決するため、ポリエチレングリコールとポリグルタミン酸からなるブロック共重合体にシスプラチンを配位結合させた配位化合物が発明されている。
(1)式I又は式II
(上記式IおよびIIにおいて、R1は、独立して、水素原子又は、官能基又は置換基により置換されていてもよいアルキル基を示し、Aは、独立して、NH、CO、R5(CH2)pR6または直接結合を示し、ここでR5はO、OCO、OCONH、NHCO、NHCOO、NHCONH、CONHまたはCOOであり、R6はNHまたはCOであり、そしてpは1〜6の整数であり;R2は、独立して、水素原子、アルカリ金属またはアルキル基またはアラルキル基を示し、R3は、独立して、水素原子、水酸基または疎水性残基を示し、nは110〜340の整数を示し、mは20〜80の整数を示す)
で表されるブロック共重合体とシスプラチンとの配位化合物を含有する液体組成物であって、当該液体組成物のpHが3.0〜7.0であることを特徴とする液体組成物;
(2)液体組成物のpHが4.0〜6.0であることを特徴とする(1)に記載の液体組成物;
(3)前記液体組成物が更に糖又は糖アルコールを含んでいることを特徴とする(1)または(2)に記載の液体組成物;
(4)糖又は糖アルコールが、D−マンニトールである(3)に記載の液体組成物。
(5)液体組成物中のD−マンニトール濃度が5%(W/V)である(4)に記載の液体組成物。
また、本発明の配位化合物は、水性媒体中で高分子ミセルを形成することができる。
式中、nは110〜340の整数を示すが、特に200〜340の整数が好ましく、mは20〜80の整数を示すが、30〜50の整数が特に好ましい。
高分子ミセルの調製
シスプラチン70gを注射用水に溶解させた溶液と、特許文献1に記載の方法で合成した共重合体、メトキシポリエチレングリコール−ポリグルタミン酸共重合体、PEG−p(Glu)(PEGの平均分子量:12,000、グルタミン酸平均残基数:40、グルタミン酸側鎖はカルボン酸)105gを注射用水に溶解した溶液とを混合し、注射用水を加えて50Lとした。この溶液を37℃で3日間反応させた。得られた溶液を、限外ろ過(分画分子量:100,000)を繰り返すことにより精製、濃縮し、D−マンニトールと注射用水を加え、高分子ミセル溶液を得た(シスプラチンとして2.5mg/mL相当、5% D−マンニトールを含有)。
高分子ミセルの安定性試験
調製した高分子ミセル溶液20mL(シスプラチンとして2.5mg/mL相当、5% D−マンニトールを含有)に、0.01mol/L塩酸又は0.01mol/L水酸化ナトリウム溶液、及び注射用水を徐々に添加してpHを3.0、4.0、5.0、6.0、7.0又は9.0に調整し、総量を25mLとした。各pHの溶液を褐色バイアルに6mLずつ分注し、密栓して5℃で保存した。2日後、下記の条件で類縁物質の量の測定を行い、残ったバイアルを40℃に移し、更に20日間保存した。保存後、同様に下記の条件で類縁物質量の測定を行った。
装置:Waters GPC system
カラム:Waters Ultrahydrogel 500,10μm,7.8φ×300mm
カラム温度:約40℃の恒温
検出器:UV検出器(検出波長280nm)
移動相:リン酸二水素ナトリウム(無水)2.87g、リン酸水素二ナトリウム・十二水和物0.24g及び塩化ナトリウム2.92gを水に溶解し、1Lとした溶液
流速:約0.6mL/分
Claims (5)
- 式I又は式II
(上記式IおよびIIにおいて、R1は、独立して、水素原子又は、官能基又は置換基により置換されていてもよいアルキル基を示し、Aは、独立して、NH、CO、R5(CH2)pR6または直接結合を示し、ここでR5はO、OCO、OCONH、NHCO、NHCOO、NHCONH、CONHまたはCOOであり、R6はNHまたはCOであり、そしてpは1〜6の整数であり;R2は、独立して、水素原子、アルカリ金属またはアルキル基またはアラルキル基を示し、R3は、独立して、水素原子、水酸基または疎水性残基を示し、nは110〜340の整数を示し、mは20〜80の整数を示す)
で表されるブロック共重合体とシスプラチンとの配位化合物を含有する液体組成物であって、当該液体組成物のpHが3.0〜7.0であることを特徴とする液体組成物。 - 液体組成物のpHが4.0〜6.0であることを特徴とする請求項1に記載の液体組成物。
- 前記液体組成物が更に糖又は糖アルコールを含んでいることを特徴とする請求項1または2に記載の液体組成物。
- 糖又は糖アルコールが、D−マンニトールである請求項3に記載の液体組成物。
- 液体組成物中のD−マンニトール濃度が5%(W/V)である請求項4に記載の液体組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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JP2010517837A JP5458255B2 (ja) | 2008-06-24 | 2009-05-27 | シスプラチン配位化合物の液体組成物 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
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JP2008164814 | 2008-06-24 | ||
JP2008164814 | 2008-06-24 | ||
PCT/JP2009/060102 WO2009157279A1 (ja) | 2008-06-24 | 2009-05-27 | シスプラチン配位化合物の液体組成物 |
JP2010517837A JP5458255B2 (ja) | 2008-06-24 | 2009-05-27 | シスプラチン配位化合物の液体組成物 |
Publications (2)
Publication Number | Publication Date |
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JPWO2009157279A1 true JPWO2009157279A1 (ja) | 2011-12-08 |
JP5458255B2 JP5458255B2 (ja) | 2014-04-02 |
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JP2010517837A Expired - Fee Related JP5458255B2 (ja) | 2008-06-24 | 2009-05-27 | シスプラチン配位化合物の液体組成物 |
Country Status (13)
Country | Link |
---|---|
US (1) | US8895076B2 (ja) |
EP (1) | EP2305275B1 (ja) |
JP (1) | JP5458255B2 (ja) |
KR (1) | KR101650907B1 (ja) |
CN (1) | CN102076345B (ja) |
AU (1) | AU2009263529B2 (ja) |
CA (1) | CA2728502C (ja) |
DK (1) | DK2305275T3 (ja) |
ES (1) | ES2425772T3 (ja) |
HK (1) | HK1154801A1 (ja) |
PL (1) | PL2305275T3 (ja) |
TW (1) | TWI428145B (ja) |
WO (1) | WO2009157279A1 (ja) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011105792A (ja) * | 2009-11-12 | 2011-06-02 | Japan Science & Technology Agency | ブロックコポリマー、ブロックコポリマー−金属錯体複合体、及びそれを用いた中空構造体キャリア |
TWI568453B (zh) * | 2011-11-22 | 2017-02-01 | 原創生醫股份有限公司 | 具有螯合型複合微胞之藥物載體及其應用 |
CN102604082B (zh) * | 2012-02-15 | 2013-12-11 | 中国科学院长春应用化学研究所 | 顺铂配合物及其制备方法 |
CN103272244A (zh) * | 2013-01-21 | 2013-09-04 | 长春理工大学 | 一种药物键合物、制法及其在治疗肿瘤的应用 |
AU2015369185B2 (en) | 2014-12-26 | 2020-10-22 | Nippon Kayaku Kabushiki Kaisha | Pharmaceutical preparation of camptothecin-containing polymer derivative |
CA2990369A1 (en) | 2015-06-24 | 2016-12-29 | Nippon Kayaku Kabushiki Kaisha | Novel platinum (iv) complex |
KR20180039628A (ko) * | 2015-09-03 | 2018-04-18 | 니폰 가야꾸 가부시끼가이샤 | 캄프토테신류 고분자 유도체를 함유하는 의약 조성물 |
JP6725520B2 (ja) | 2015-09-14 | 2020-07-22 | 日本化薬株式会社 | 6配位白金錯体の高分子結合体 |
EP3395857B1 (en) | 2015-12-22 | 2021-05-26 | Nippon Kayaku Kabushiki Kaisha | Polymer conjugate of sulfoxide derivative-coordinated platinum(ii) complex |
JPWO2018038240A1 (ja) * | 2016-08-26 | 2019-06-24 | 公益財団法人川崎市産業振興財団 | 金属とブロック共重合体との錯体を含むミセルを安定化させる方法および安定化されたミセル、並びにミセルからの金属の放出制御法 |
WO2019217328A1 (en) | 2018-05-07 | 2019-11-14 | California Institute Of Technology | Gel and polymer based flow meters |
CN109908084B (zh) * | 2019-04-11 | 2021-06-25 | 临沂大学 | 一种铂交联喜树碱前药胶束纳米药物及其制备方法和应用 |
US11668613B2 (en) * | 2019-05-06 | 2023-06-06 | California Institute Of Technology | ABA type block co-polymers for temperature sensing and flow meters |
CN112121176B (zh) * | 2019-06-24 | 2022-07-01 | 山东华铂凯盛生物科技有限公司 | 一种顺铂微粒组成、制备方法及应用 |
US11912807B2 (en) | 2020-03-25 | 2024-02-27 | Samsung Electronics Co., Ltd. | Composite for sensing heat or infrared light and device including same |
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BR9604895A (pt) | 1995-04-14 | 1999-11-30 | Kazunori Kataoka | Polioxietileno tendo um açúcar em uma extremidade e um grupo funcional diferente na outra extremidade, e um processo para a produção do mesmo |
NZ305471A (en) | 1995-04-19 | 2000-02-28 | Kazunori Kataoka | Use of heterotelechelic block copolymers as carriers for medicaments |
BR9610053A (pt) | 1995-08-10 | 1999-07-06 | Katoaka Kazunori | Polímetro de blocos tendo grupos funcionais sobre ambas extremidades |
DE60121016T2 (de) | 2000-09-26 | 2006-12-21 | Toudai Tlo, Ltd. | Polymere mizelle mit darin eingeschlossenem cisplatin und ihre verwendung |
US7094810B2 (en) * | 2001-06-08 | 2006-08-22 | Labopharm, Inc. | pH-sensitive block copolymers for pharmaceutical compositions |
JP2003012505A (ja) * | 2001-07-06 | 2003-01-15 | Nano Career Kk | 薬物含有高分子ミセルの凍結乾燥 |
WO2006057429A1 (ja) * | 2004-11-24 | 2006-06-01 | Nanocarrier Co., Ltd. | ブロックコポリマーのモーフォロジ-の変化方法 |
WO2007066781A1 (ja) * | 2005-12-05 | 2007-06-14 | Nanocarrier Co., Ltd. | フッ素系有機溶媒を用いた薬物封入ポリマーミセルを含有する医薬組成物の製造方法 |
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2009
- 2009-05-27 JP JP2010517837A patent/JP5458255B2/ja not_active Expired - Fee Related
- 2009-05-27 ES ES09769989T patent/ES2425772T3/es active Active
- 2009-05-27 DK DK09769989.6T patent/DK2305275T3/da active
- 2009-05-27 US US13/001,006 patent/US8895076B2/en active Active
- 2009-05-27 EP EP09769989.6A patent/EP2305275B1/en active Active
- 2009-05-27 PL PL09769989T patent/PL2305275T3/pl unknown
- 2009-05-27 KR KR1020107028751A patent/KR101650907B1/ko active IP Right Grant
- 2009-05-27 WO PCT/JP2009/060102 patent/WO2009157279A1/ja active Application Filing
- 2009-05-27 CN CN2009801238118A patent/CN102076345B/zh not_active Expired - Fee Related
- 2009-05-27 CA CA2728502A patent/CA2728502C/en active Active
- 2009-05-27 AU AU2009263529A patent/AU2009263529B2/en not_active Ceased
- 2009-06-03 TW TW098118350A patent/TWI428145B/zh not_active IP Right Cessation
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- 2011-08-30 HK HK11109137.2A patent/HK1154801A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
US20110110881A1 (en) | 2011-05-12 |
CA2728502C (en) | 2017-01-03 |
AU2009263529B2 (en) | 2013-09-26 |
ES2425772T3 (es) | 2013-10-17 |
KR20110038629A (ko) | 2011-04-14 |
TWI428145B (zh) | 2014-03-01 |
HK1154801A1 (en) | 2012-05-04 |
WO2009157279A1 (ja) | 2009-12-30 |
DK2305275T3 (da) | 2013-10-07 |
CN102076345A (zh) | 2011-05-25 |
PL2305275T3 (pl) | 2013-12-31 |
JP5458255B2 (ja) | 2014-04-02 |
US8895076B2 (en) | 2014-11-25 |
EP2305275A1 (en) | 2011-04-06 |
EP2305275A4 (en) | 2012-07-18 |
KR101650907B1 (ko) | 2016-08-24 |
EP2305275B1 (en) | 2013-07-10 |
TW201006497A (en) | 2010-02-16 |
CN102076345B (zh) | 2013-05-08 |
CA2728502A1 (en) | 2009-12-30 |
AU2009263529A1 (en) | 2009-12-30 |
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