JPWO2005034990A1 - アンチトロンビンiii含有止血用組成物 - Google Patents
アンチトロンビンiii含有止血用組成物 Download PDFInfo
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- JPWO2005034990A1 JPWO2005034990A1 JP2005514578A JP2005514578A JPWO2005034990A1 JP WO2005034990 A1 JPWO2005034990 A1 JP WO2005034990A1 JP 2005514578 A JP2005514578 A JP 2005514578A JP 2005514578 A JP2005514578 A JP 2005514578A JP WO2005034990 A1 JPWO2005034990 A1 JP WO2005034990A1
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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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
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- 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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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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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
- A61K9/14—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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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Description
FVIIa/FX混合物の緩衝溶液中の安定性を調べる目的で、所定のpHを有する各々の緩衝液(CaCl2非存在下、クエン酸緩衝液:10mMクエン酸ナトリウム、120mM NaCl、0.5%グリシン、2%アルブミン、50ppmツイーン80)下に、FVIIa及びFXを終濃度0.6mg/mL(約12μM)及び6.0mg/mL(約100μM)になるよう混合し、室温で放置した。各放置時間後のサンプル中のFVIIa活性、FX活性及びFXa活性はそれぞれの因子が影響することのない系を用いて測定した。なお、ここで用いたFVIIaは、特開平3−155797号公報に記載の方法による血液由来の標品である。また、ここで用いたFXは、新鮮凍結ヒト血漿を冷融解・遠心処理してクリオプレシピテートを除いた脱クリオ血漿から、陰イオン交換クロマトグラフィーにより粗精製後、抗FXモノクローナル抗体固定化カラムを用いてのアフィニティークロマトグラフィーによって製された血液由来の標品であった。
FVIIa/FX混合物の緩衝溶液中の安定性を高める目的で、実施例1に示した各pHを有する各々の緩衝液下に、FVIIaおよびFXを終濃度0.6mg/mL及び6.0mg/mLになるよう混合し、さらにAT−IIIを終濃度1.0国際単位/mLになるよう添加し、室温で放置した。各放置時間後のサンプル中のFVIIa活性、FX活性及びFXa活性はそれぞれの因子が影響することのない系を用いて測定した。なお、ここで用いたFVIIa、FXは実施例1と同じく調製した。また、ここで用いたAT−IIIは、新鮮凍結ヒト血漿を冷融解・遠心処理してクリオプレシピテートを除いた脱クリオ血漿から、ヘパリンアフィニティークロマトグラフィーにより粗精製後、沈殿分画により製された血液由来の標品であった。
FVIIa/FX混合物の緩衝溶液中の安定性を高めるために要するAT−IIIの濃度を調べる目的で、実施例1に示した緩衝液組成のpH5.7条件下に、FVIIaおよびFXを終濃度0.6mg/mL及び6.0mg/mLになるよう混合し、さらにAT−IIIを終濃度0、0.1、0.2、0.5、1.0国際単位/mLになるよう添加し、室温で放置した。各放置時間後のサンプル中のFVIIa活性、FX活性及びFXa活性については実施例1と同様の方法にて測定した。なお、ここで用いたFVIIa、FXは実施例1と同じく調製した。また、ここで用いたAT−IIIは、実施例2と同じく調製した。
Claims (10)
- 分離精製した活性化血液凝固第VII因子(FVIIa)及び血液凝固第X因子(FX)を単一容器内に混合して含有する溶液状止血用組成物に、さらにアンチトロンビンIII(AT−III)を加えたことを特徴とする、薬剤学的に安定な溶液状止血用組成物。
- 含有されるFVIIa、FX及びAT−IIIの濃度が各々1〜20μM、5〜400μM及び0.1〜5.0国際単位/mLである、請求項1記載の溶液状止血用組成物。
- pHが5.0を超える範囲である、請求項1または2記載の溶液状止血用組成物。
- pHが5.0を超え、7.0未満の酸性領域にある、請求項3記載の溶液状止血用組成物。
- pHが5.5以上、6.5以下の酸性領域にある、請求項3記載の溶液状止血用組成物。
- 請求項1〜5のいずれかに記載の溶液状止血用組成物を凍結乾燥してなる凍結乾燥止血用製剤。
- FVIIa及びFXを単一容器内に混合して含有する溶液状止血用組成物にAT−IIIを加えることを特徴とする当該溶液状止血用組成物の安定化方法。
- 該組成物のpHが5.0を超える範囲である、請求項7記載の方法。
- 該組成物のpHが5.0を超え、7.0未満の酸性領域にある、請求項8記載の方法。
- 該組成物のpHが5.5以上、6.5以下の酸性領域にある、請求項8記載の方法。
Applications Claiming Priority (3)
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JP2003350179 | 2003-10-09 | ||
JP2003350179 | 2003-10-09 | ||
PCT/JP2004/014731 WO2005034990A1 (ja) | 2003-10-09 | 2004-10-06 | アンチトロンビンiii含有止血用組成物 |
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JPWO2005034990A1 true JPWO2005034990A1 (ja) | 2007-11-22 |
JP4613133B2 JP4613133B2 (ja) | 2011-01-12 |
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JP2005514578A Active JP4613133B2 (ja) | 2003-10-09 | 2004-10-06 | アンチトロンビンiii含有止血用組成物 |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02167234A (ja) * | 1988-07-14 | 1990-06-27 | Furukawa Fuaamashii:Kk | 生体組織接着剤 |
WO2003006054A1 (fr) * | 2001-07-10 | 2003-01-23 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Compositions hemostatiques pharmaceutiquement stables |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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AT359646B (de) * | 1979-04-19 | 1980-11-25 | Immuno Ag | Verfahren zur herstellung von nebenwirkungs- freien plasmafraktionen |
DE3336314C1 (de) * | 1983-10-06 | 1984-08-16 | Bochumer Eisenhütte Heintzmann GmbH & Co KG, 4630 Bochum | Bohrlafette |
DD251078A1 (de) * | 1986-07-17 | 1987-11-04 | Bezirksinstitut Fuer Blutspend | Verfahren zur herstellung von prothrombinkonzentraten |
AT408613B (de) * | 1998-06-17 | 2002-01-25 | Immuno Ag | Pharmazeutisches faktor vii-präparat |
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- 2004-10-06 WO PCT/JP2004/014731 patent/WO2005034990A1/ja active Application Filing
- 2004-10-06 JP JP2005514578A patent/JP4613133B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02167234A (ja) * | 1988-07-14 | 1990-06-27 | Furukawa Fuaamashii:Kk | 生体組織接着剤 |
WO2003006054A1 (fr) * | 2001-07-10 | 2003-01-23 | Juridical Foundation The Chemo-Sero-Therapeutic Research Institute | Compositions hemostatiques pharmaceutiquement stables |
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JP4613133B2 (ja) | 2011-01-12 |
WO2005034990A1 (ja) | 2005-04-21 |
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