JP4886517B2 - 新たな用途の薬学的調製物およびその調製物を製造するためのプロセス - Google Patents
新たな用途の薬学的調製物およびその調製物を製造するためのプロセス Download PDFInfo
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- JP4886517B2 JP4886517B2 JP2006533996A JP2006533996A JP4886517B2 JP 4886517 B2 JP4886517 B2 JP 4886517B2 JP 2006533996 A JP2006533996 A JP 2006533996A JP 2006533996 A JP2006533996 A JP 2006533996A JP 4886517 B2 JP4886517 B2 JP 4886517B2
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- ifosfamide
- mesna
- solution
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
本発明は、非経口投与のための、保存安定性の濃縮および/または高濃縮(過飽和)水性薬学的調製物、保存安定性の濃縮および/または高濃縮(過飽和)水性薬学的イフォスファミド(Ifosfamide)調製物中へのイフォスファミドの溶解度を増大するための、メルカプトエタンスルホネート−ナトリウム(メスナ(Mesna))の使用、ならびにそれらを製造するためのプロセスに関する。
イフォスファミド(Ifosfamide)(2−(クロルエチルアミノ)−3−(2−クロルエチル)−テトラヒドロ−2H−1,3,2−オキサザホスホリン−2−オキシド)は、時々他の細胞増殖抑制剤と組み合わせて、種々の腫瘍疾患に対して投与される、アルキル化細胞増殖抑制剤である。メスナ(Mesna)(メルカプトエタンスルホネート−ナトリウム)は、イフォスファミドの副作用を減少させるために、イフォスファミドと同時投与される(特許文献1および特許文献2;特許文献3を参照のこと)。
驚くべきことに、メルカプトエタンスルホネート−ナトリウム(メスナ)の使用によって、高濃縮(過飽和)イフォスファミド水性溶液が、成功裏に調製され得、この溶液の濃度は、水へのイフォスファミドの飽和濃度より実質的に上であることが見出された。室温での約140mg/mlの飽和濃度および約5℃での約190mg/mlの飽和濃度は、メスナの使用によって、十分なゆとりで上回ることができる。溶解度増加剤としてメスナを使用することによって、約10%(重量/容積)〜50%(重量/容積)の濃度範囲のイフォスファミドの物理的特性に関して、保存安定性濃度のイフォスファミドを、うまく製造することができる。
(20%(重量/容積)メスナ含量を有する、20%(重量/容積)イフォスファミド濃縮物)
溶液の組成:
イフォスファミド 2000.0mg
メスナ 2000.0mg
リン酸緩衝剤 1000.0mg
水(WFI) 6540.0mg
製造において、注射用水の90%を、約5℃〜10℃に冷却し、この注射用水にリン酸緩衝剤を溶解する;次にメスナを添加し、均一に溶解する。最後に、イフォスファミドを上記溶液に溶解し、オルトリン酸を使用してpHを7.4に設定する。このように得られた溶液を、冷却注射用水を用いて特定の重量にし、無菌濾過し、そして無菌条件下で注射バイアル中に充填する。滅菌および充填は、冷却下では行わない。
(5%(重量/容積)メスナを有する、20%(重量/容積)イフォスファミド濃縮物)
溶液の組成:
イフォスファミド 2000.0mg
メスナ 500.0mg
リン酸緩衝剤 1000.0mg
水(WFI) 8040.0mg
この溶液を、実施例1の手順に従って同様に製造する。
(5%(重量/容積)メスナを有する、20%(重量/容積)イフォスファミド濃縮物、凍結乾燥物およびその凍結乾燥物の再構成物)
充填前かつ再構成後の溶液の組成:
イフォスファミド 2000.0mg
メスナ 500.0mg
マンニトール 500.0mg
水(WFI) 8040.0mg
製造において、順番に、メスナ、イフォスファミドおよびマンニトールを、約5℃〜10℃に予冷した注射用水の約90%に添加し、それによって、各々を、透明な溶液が得られるまでホモジナイズする。続いて、この溶液を無菌濾過し、注射バイアル中に無菌条件下で凍結乾燥のための特定の重量まで充填する。凍結乾燥を、適切な凍結乾燥デバイスおよび以下の凍結乾燥プロセスを使用して行う:例えば、
凍結 −45℃で1時間
−45℃に維持して3.5時間;
主乾燥 0.4mbar、−45℃〜−15℃で1.5時間以内
0.4mbar、−15℃で120時間;
乾燥後 0.4mbar、4時間かけて20℃に上昇させる
最大減圧、20℃で6時間;
上記注射バイアルを、窒素下で密封する;
凍結乾燥物の組成:
イフォスファミド 2000.0mg
メスナ 500.0mg
マンニトール 500.0mg
凍結乾燥物の再構成。
(5%(重量/容積)メスナを有する、12%(重量/容積)イフォスファミド濃縮物)
イフォスファミド 3g
メスナ 1.25g
水 24.5g。
(10%(重量/容積)メスナを有する、25%(重量/容積)イフォスファミド濃縮物)
イフォスファミド 6.25g
メスナ 2.5g
水 23.75g。
(20%(重量/容積)メスナを有する、50%(重量/容積)イフォスファミド濃縮物)
イフォスファミド 12.5g
メスナ 5.0g
水 17.5g。
Claims (3)
- イフォスファミドをその水中での飽和濃度を超える含量で非経口投与するための水性薬学的調製物の製造においてイフォスファミドの溶解度促進剤としてのメスナの使用であって、イフォスファミドのメスナに対する重量比は、1:0.25〜1:4の範囲にあり、ここで、該調製物は、エーテル化β−シクロデキストリンを含まない、使用。
- 前記水性薬学的調製物は、補助剤を含み、該補助剤は、塩化ナトリウムおよびマンニトールからなる群より選択される、請求項1に記載の使用。
- pHが、リン酸緩衝剤、ホウ酸緩衝剤、および炭酸緩衝剤からなる群より選択される緩衝剤によってpH6〜8に設定される、請求項1に記載の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US50775003P | 2003-10-01 | 2003-10-01 | |
US60/507,750 | 2003-10-01 | ||
PCT/US2004/031650 WO2005032515A1 (en) | 2003-10-01 | 2004-09-28 | New use, pharmaceutical preparations as well as a process for their production |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011088613A Division JP2011137048A (ja) | 2003-10-01 | 2011-04-12 | 新たな用途の薬学的調製物およびその調製物を製造するためのプロセス |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007507506A JP2007507506A (ja) | 2007-03-29 |
JP4886517B2 true JP4886517B2 (ja) | 2012-02-29 |
Family
ID=34421657
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006533996A Active JP4886517B2 (ja) | 2003-10-01 | 2004-09-28 | 新たな用途の薬学的調製物およびその調製物を製造するためのプロセス |
JP2011088613A Withdrawn JP2011137048A (ja) | 2003-10-01 | 2011-04-12 | 新たな用途の薬学的調製物およびその調製物を製造するためのプロセス |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011088613A Withdrawn JP2011137048A (ja) | 2003-10-01 | 2011-04-12 | 新たな用途の薬学的調製物およびその調製物を製造するためのプロセス |
Country Status (13)
Country | Link |
---|---|
US (1) | US8093230B2 (ja) |
EP (1) | EP1667655B1 (ja) |
JP (2) | JP4886517B2 (ja) |
AT (1) | ATE516014T1 (ja) |
CA (1) | CA2540537A1 (ja) |
CY (1) | CY1111960T1 (ja) |
DK (1) | DK1667655T3 (ja) |
ES (1) | ES2369776T3 (ja) |
HK (1) | HK1091146A1 (ja) |
PL (1) | PL1667655T3 (ja) |
PT (1) | PT1667655E (ja) |
SI (1) | SI1667655T1 (ja) |
WO (1) | WO2005032515A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1958618A1 (de) | 2007-02-15 | 2008-08-20 | Octapharma AG | Verfahren zur Gefriertrocknung mit optimierter Rekonstitution von Biopolymeren |
EP2994062B1 (en) * | 2013-05-07 | 2019-10-02 | AuXin Surgery SA | Device for chemically assisted dissection |
US20160324809A1 (en) * | 2014-01-06 | 2016-11-10 | Auxin Surgery Sa | Lyophilized mesna compositions |
CA3017403A1 (en) * | 2016-03-14 | 2017-09-21 | Auxin Surgery Sa | Device, method and formulation for chemically assisted dissection |
BE1024110B1 (fr) * | 2016-10-18 | 2017-11-16 | Auxin Surgery Sa | Dispositif, procédé et formulation pour dissection assistée de manière chimique |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3732340A (en) * | 1966-07-11 | 1973-05-08 | Asta Werke Ag Chem Fab | N',o-propylene phosphoric acid ester diamides |
US4220660A (en) * | 1977-12-14 | 1980-09-02 | Asta-werke Aktiengesellschaft, Chemische Farik | Process for the treatment of humans suffering from undesired urotoxic side effects caused by cytostatically active alkylating agents |
US5204335A (en) * | 1986-10-31 | 1993-04-20 | Asta Pharma Aktiengesellschaft | Ifosfamide lyophilisate and process for its preparation |
DE3862595D1 (de) * | 1987-03-06 | 1991-06-06 | Asta Pharma Ag | Verfahren zur herstellung von ifosfamid mit verbesserten eigenschaften. |
ES2040394T3 (es) * | 1988-03-19 | 1993-10-16 | Asta Medica Aktiengesellschaft | Procedimiento para preparar un material liofilizado de ifosfamida y mesna. |
US5227373A (en) * | 1991-10-23 | 1993-07-13 | Bristol-Myers Squibb Co. | Lyophilized ifosfamide compositions |
DE19529057B4 (de) * | 1995-08-08 | 2007-12-13 | Baxter Healthcare S.A. | Ifosfamid-Lyophilisat-Zubereitungen |
DE19540132C2 (de) * | 1995-10-27 | 2003-04-03 | Stada Arzneimittel Ag | Ifosfamid-Lyophilisat |
AU2002359695A1 (en) * | 2001-12-13 | 2003-06-30 | Sicor Inc. | Aqueous ifosfamide composition |
US6613927B1 (en) * | 2002-02-08 | 2003-09-02 | American Pharmaceutical Partners, Inc. | Sterile lyophilized ifosfamide and associated methods |
BR0314068A (pt) * | 2002-09-05 | 2005-07-05 | Bharat Serums & Vaccines Ltd | Processo para a preparação de uma composição estável com baixo nìvel de toxicidade; composição estável que contém oxazafosforina; uso de uma composição estável que contém oxazafosforina; e método de tratamento de uma doença maligna |
US7199111B2 (en) * | 2002-12-02 | 2007-04-03 | Bharat Serums & Vaccines Ltd. | Aqueous ifosfamide compositions for parenteral administration and a process for their preparations |
-
2004
- 2004-09-28 ES ES04789095T patent/ES2369776T3/es active Active
- 2004-09-28 SI SI200431734T patent/SI1667655T1/sl unknown
- 2004-09-28 CA CA002540537A patent/CA2540537A1/en not_active Abandoned
- 2004-09-28 DK DK04789095.9T patent/DK1667655T3/da active
- 2004-09-28 PL PL04789095T patent/PL1667655T3/pl unknown
- 2004-09-28 PT PT04789095T patent/PT1667655E/pt unknown
- 2004-09-28 WO PCT/US2004/031650 patent/WO2005032515A1/en active Application Filing
- 2004-09-28 US US10/952,027 patent/US8093230B2/en not_active Expired - Fee Related
- 2004-09-28 JP JP2006533996A patent/JP4886517B2/ja active Active
- 2004-09-28 AT AT04789095T patent/ATE516014T1/de active
- 2004-09-28 EP EP04789095A patent/EP1667655B1/en active Active
-
2006
- 2006-11-29 HK HK06113073.7A patent/HK1091146A1/xx not_active IP Right Cessation
-
2011
- 2011-04-12 JP JP2011088613A patent/JP2011137048A/ja not_active Withdrawn
- 2011-09-05 CY CY20111100847T patent/CY1111960T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
US8093230B2 (en) | 2012-01-10 |
ES2369776T3 (es) | 2011-12-05 |
CY1111960T1 (el) | 2015-11-04 |
EP1667655A1 (en) | 2006-06-14 |
SI1667655T1 (sl) | 2011-10-28 |
CA2540537A1 (en) | 2005-04-14 |
PL1667655T3 (pl) | 2012-05-31 |
HK1091146A1 (en) | 2007-01-12 |
US20050124589A1 (en) | 2005-06-09 |
JP2007507506A (ja) | 2007-03-29 |
DK1667655T3 (da) | 2011-10-24 |
JP2011137048A (ja) | 2011-07-14 |
EP1667655B1 (en) | 2011-07-13 |
WO2005032515A1 (en) | 2005-04-14 |
ATE516014T1 (de) | 2011-07-15 |
PT1667655E (pt) | 2011-08-18 |
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