JP2007174978A - Adamts13の安定化方法 - Google Patents
Adamts13の安定化方法 Download PDFInfo
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- JP2007174978A JP2007174978A JP2005377270A JP2005377270A JP2007174978A JP 2007174978 A JP2007174978 A JP 2007174978A JP 2005377270 A JP2005377270 A JP 2005377270A JP 2005377270 A JP2005377270 A JP 2005377270A JP 2007174978 A JP2007174978 A JP 2007174978A
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- adamts13
- ion
- divalent metal
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- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 8
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- 239000000203 mixture Substances 0.000 claims abstract description 25
- 229910021645 metal ion Inorganic materials 0.000 claims abstract description 21
- 102000004190 Enzymes Human genes 0.000 claims abstract description 19
- 108090000790 Enzymes Proteins 0.000 claims abstract description 19
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910001424 calcium ion Inorganic materials 0.000 claims abstract description 9
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910001422 barium ion Inorganic materials 0.000 claims abstract description 5
- 229910001425 magnesium ion Inorganic materials 0.000 claims abstract description 5
- 108010047303 von Willebrand Factor Proteins 0.000 claims abstract description 4
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- 238000010438 heat treatment Methods 0.000 claims description 5
- 230000002779 inactivation Effects 0.000 claims description 5
- 102100036537 von Willebrand factor Human genes 0.000 claims description 5
- 229910001437 manganese ion Inorganic materials 0.000 claims description 4
- 230000006641 stabilisation Effects 0.000 claims description 3
- 238000011105 stabilization Methods 0.000 claims description 3
- 229960001134 von willebrand factor Drugs 0.000 claims description 3
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 claims description 2
- 102100032290 A disintegrin and metalloproteinase with thrombospondin motifs 13 Human genes 0.000 claims 8
- 102000043853 ADAMTS13 Human genes 0.000 abstract description 45
- 230000000694 effects Effects 0.000 abstract description 24
- 239000003814 drug Substances 0.000 abstract description 2
- 238000004321 preservation Methods 0.000 abstract 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 11
- 239000001110 calcium chloride Substances 0.000 description 11
- 229910001628 calcium chloride Inorganic materials 0.000 description 11
- 238000003860 storage Methods 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 3
- 201000007023 Thrombotic Thrombocytopenic Purpura Diseases 0.000 description 3
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- -1 nitric acid compound Chemical class 0.000 description 3
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- 239000000523 sample Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 208000004886 acquired thrombotic thrombocytopenic purpura Diseases 0.000 description 2
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 2
- 229910001626 barium chloride Inorganic materials 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 239000004023 fresh frozen plasma Substances 0.000 description 2
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- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000035888 Immune-mediated thrombotic thrombocytopenic purpura Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
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- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 229940099607 manganese chloride Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
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- 229960000380 propiolactone Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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- Enzymes And Modification Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
【解決手段】ADAMTS13を含む組成物にカルシウムイオンやバリウムイオン、マグネシウムイオンに代表される2価金属イオンを添加する。熱安定性及び保存安定性の改善に大きな効果があり、治療用医薬品として有用である。
【選択図】なし
Description
1、フォンヴィルブランド因子切断酵素(ADAMTS13)を含む組成物に2価金属イオンを含有させることを特徴するADAMTS13の安定化方法。
2、カルシウムイオン、バリウムイオン、マンガンイオン又はマグネシウムイオンのうちから選択された少なくとも1種を含有させる上記1に記載のADAMTS13の安定化方法。
3、2価金属イオンを含有させることを特徴とするADAMTS13を含む組成物。
4、2価金属イオンを含有させる工程を用いることを特徴とするADAMTS13又はその含有組成物の製造方法。
5、2価金属イオンを含有させてなるADAMTS13又はその含有組成物の加熱処理方法。
6、上記4または5のいずれかに記載の工程とウイルス不活化工程を組み合わせて調製するADAMTS13又はその含有組成物。
少なくとも1.5mMで認められた。通常3〜20mMの添加で十分な効果が得られる。
本発明において用いられる2価金属イオンは、塩化物、硝酸化合物、酢酸化合物、乳酸化合物等の塩類が用いられるが、その対イオン種については特に限定されるものではない。
本発明の方法又は製造方法を用いた、液状又は乾燥加熱処理を組合せることができる。
活性を100%としたときの相対活性で表したところ、45℃、20分間のインキュベーションで対照は約4分の1の残存活性しか示さないのに対して、2価金属イオンを加えたものでは何れもほぼ完全に活性を保持していることから、2価金属イオンの添加による熱安定性の向上が確認できた。塩化カルシウムの添加は56℃でもほぼ完全に活性を保持していた。また、塩化カルシウムおよび塩化バリウムを加えた場合には、ADAMTS13の活性自体が約2倍に増強された。
Claims (6)
- フォンヴィルブランド因子切断酵素(ADAMTS13)を含む組成物に2価金属イオンを含有させることを特徴するADAMTS13の安定化方法。
- カルシウムイオン、バリウムイオン、マンガンイオン又はマグネシウムイオンのうちから選択された少なくとも1種を含有させる請求項1に記載のADAMTS13の安定化方法。
- 2価金属イオンを含有させることを特徴とするADAMTS13を含む組成物。
- 2価金属イオンを含有させる工程を用いることを特徴とするADAMTS13又はその含有組成物の製造方法。
- 2価金属イオンを含有させてなるADAMTS13又はその含有組成物の加熱処理方法。
- 請求項4又は5のいずれかに記載の工程とウイルス不活化工程を組み合わせて調製するADAMTS13又はその含有組成物。
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JP2005377270A JP4880997B2 (ja) | 2005-12-28 | 2005-12-28 | Adamts13の安定化方法 |
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JP2005377270A JP4880997B2 (ja) | 2005-12-28 | 2005-12-28 | Adamts13の安定化方法 |
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JP2007174978A true JP2007174978A (ja) | 2007-07-12 |
JP4880997B2 JP4880997B2 (ja) | 2012-02-22 |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110086413A1 (en) * | 2009-07-31 | 2011-04-14 | Baxter International Inc. | Cell Culture Medium For ADAMTS Protein Expression |
WO2011035335A3 (en) * | 2009-09-21 | 2011-12-01 | Baxter International Inc. | Stabilized liquid and lyophilized adamts13 formulations |
-
2005
- 2005-12-28 JP JP2005377270A patent/JP4880997B2/ja active Active
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9127265B2 (en) | 2009-07-31 | 2015-09-08 | Baxalta Incorporated | Cell culture medium for ADAMTS protein expression |
US11254921B2 (en) | 2009-07-31 | 2022-02-22 | Takeda Pharmaceutical Company Limited | ADAMTS13 protein cell culture supernatant |
US10724024B2 (en) | 2009-07-31 | 2020-07-28 | Baxalta Incorporated | Cell culture methods for expressing ADAMTS protein |
US10072254B2 (en) | 2009-07-31 | 2018-09-11 | Baxalta Incorporated | Cell culture methods for expressing ADAMTS13 protein |
US8313926B2 (en) * | 2009-07-31 | 2012-11-20 | Baxter International Inc. | Methods for expressing ADAMTS proteins in cell culture medium supplemented with zinc |
US9441216B2 (en) | 2009-07-31 | 2016-09-13 | Baxalta Incorporated | Cell culture medium for ADAMTS protein expression |
US20130071906A1 (en) * | 2009-07-31 | 2013-03-21 | Baxter Healthcare S.A. | Cell culture medium for adamts protein expression |
US20110086413A1 (en) * | 2009-07-31 | 2011-04-14 | Baxter International Inc. | Cell Culture Medium For ADAMTS Protein Expression |
US8759026B2 (en) | 2009-07-31 | 2014-06-24 | Baxter International Inc. | Methods for increasing recovery of an ADAMTS activity from a cell culture supernatant |
US9351935B2 (en) | 2009-09-21 | 2016-05-31 | Baxalta Incorporated | Stabilized liquid and lyophilized ADAMTS13 formulations |
KR101891646B1 (ko) * | 2009-09-21 | 2018-08-27 | 박스알타 인코퍼레이티드 | 안정화된 액체 및 동결건조된 adamts13 제제 |
AU2010295299B2 (en) * | 2009-09-21 | 2015-12-24 | Takeda Pharmaceutical Company Limited | Stabilized liquid and lyophilized ADAMTS13 formulations |
US8623352B2 (en) | 2009-09-21 | 2014-01-07 | Baxter International Inc. | Stabilized liquid and lyophilized ADAMTS13 formulations |
JP2013505270A (ja) * | 2009-09-21 | 2013-02-14 | バクスター・インターナショナル・インコーポレイテッド | 安定化された液体および凍結乾燥adamts13製剤 |
EA024267B1 (ru) * | 2009-09-21 | 2016-09-30 | Баксалта Инкорпорейтид | Стабилизированные жидкие и лиофилизированные композиции adamts13 |
US9572778B2 (en) | 2009-09-21 | 2017-02-21 | Baxalta Incorporated | Stabilized liquid and lyophilized ADAMTS13 formulations |
EP3167897A1 (en) * | 2009-09-21 | 2017-05-17 | Baxalta GmbH | Stabilized liquid and lyophilized adamts13 formulations |
US9937244B2 (en) | 2009-09-21 | 2018-04-10 | Baxalta Incorporated | Stabilized liquid and lyophilized ADAMTS13 formulations |
CN104224705A (zh) * | 2009-09-21 | 2014-12-24 | 巴克斯特国际公司 | 稳定化的液体和冻干的adamts13制剂 |
KR20120099646A (ko) * | 2009-09-21 | 2012-09-11 | 박스터 헬쓰케어 에스.에이. | 안정화된 액체 및 동결건조된 adamts13 제제 |
US10238720B2 (en) | 2009-09-21 | 2019-03-26 | Baxalta Incorporated | Stabilized liquid and lyophilized ADAMTS13 formulations |
CN102573792A (zh) * | 2009-09-21 | 2012-07-11 | 巴克斯特国际公司 | 稳定化的液体和冻干的adamts13制剂 |
US10758599B2 (en) | 2009-09-21 | 2020-09-01 | Baxalta Incorporated | Stabilized liquid and lyophilized ADAMTS13 formulations |
EP3834841A1 (en) * | 2009-09-21 | 2021-06-16 | Takeda Pharmaceutical Company Limited | Stabilized liquid and lyophilized adamts13 formulations |
WO2011035335A3 (en) * | 2009-09-21 | 2011-12-01 | Baxter International Inc. | Stabilized liquid and lyophilized adamts13 formulations |
US11564979B2 (en) | 2009-09-21 | 2023-01-31 | Takeda Pharmaceutical Company Limited | Stabilized liquid and lyophilized ADAMTS13 formulations |
EP4218797A1 (en) * | 2009-09-21 | 2023-08-02 | Takeda Pharmaceutical Company Limited | Stabilized liquid and lyophilized adamts13 formulations |
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