JP5665264B2 - 安定なd−ダイマー液体製剤 - Google Patents
安定なd−ダイマー液体製剤 Download PDFInfo
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- JP5665264B2 JP5665264B2 JP2008145293A JP2008145293A JP5665264B2 JP 5665264 B2 JP5665264 B2 JP 5665264B2 JP 2008145293 A JP2008145293 A JP 2008145293A JP 2008145293 A JP2008145293 A JP 2008145293A JP 5665264 B2 JP5665264 B2 JP 5665264B2
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/745—Assays involving non-enzymic blood coagulation factors
- G01N2333/75—Fibrin; Fibrinogen
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/105831—Protein or peptide standard or control [e.g., hemoglobin, etc.]
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- Urology & Nephrology (AREA)
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Description
D−ダイマーを得るために、血餅溶解血漿を正常ヒト血漿から、トロンビンを添加し、続いてウロキナーゼを添加することにより調製した。このようにして調製した血餅溶解血漿は1193mg/l FEUのD−ダイマーを含有しており、そしてこれを緩衝マトリクスに基づく以下の製剤の製造のためのD−ダイマー製剤として使用した:
処方1:3mg/l FEU D−ダイマー
50mM NaH2PO4
10g/lのウシ血清アルブミン
0.1%(v/v) Tween(登録商標)20
80000KIU/lのアプロチニン
0.04%(w/v)アジ化ナトリウム
pH 6.9
処方2:3mg/l FEU D−ダイマー
50mM NaH2PO4
10g/lのウシ血清アルブミン
0.1%(v/v) Tween(登録商標)20
80000KIU/lのアプロチニン
0.04%(w/v)アジ化ナトリウム
0.25g/lのヒト凝固性フィブリノゲン
(Sigma-Aldrich、カタログ番号:F4883)
pH6.9
本発明の製剤の+37℃でのプレインキュベーションの効果を調べるために、10Lの処方2に従うフィブリノゲン含有D−ダイマー製剤(実施例1を参照のこと)を調製した。この製剤の一部を室温にて成分を混合した後1週間+2〜+8℃で貯蔵した。これと並行して、この製剤のさらに一部を+37℃で1週間貯蔵(プレインキュベート)した。続いて、各場合で、2つのバッチの一部を+2〜+8℃(望ましい貯蔵温度)又は+37℃(加速された貯蔵寿命データの生成のため)で貯蔵した。適切な貯蔵期間の後、D−ダイマー濃度を決定した(実施例1を参照のこと)。結果を図3及び図4に示す。
Claims (17)
- D−ダイマーを含有する緩衝マトリクスで構成される組成物であって、該緩衝マトリクスがさらに0.1g/l〜1g/lの最終濃度でフィブリノゲンを含有する組成物。
- フィブリノゲンがヒト又は動物のフィブリノゲンである、請求項1に記載の組成物。
- 緩衝マトリクスが、0.2g/l〜0.5g/lの最終濃度でフィブリノゲンを含有する、請求項1又は2に記載の組成物。
- 組成物が液体である、請求項1〜3のいずれか1項に記載の組成物。
- 緩衝マトリクスが、0.1〜100mg/l FEUのD−ダイマーを含有する、請求項1〜4のいずれか1項に記載の組成物。
- ウシ血清アルブミン、及び/又はプロテアーゼ阻害剤及び/又は界面活性剤及び/又は殺菌性作用及び/又は殺真菌性作用を有する添加剤をさらに含有する、請求項1〜5のいずれか1項に記載の組成物。
- 殺菌性作用及び殺真菌性作用を有する添加剤がアジ化ナトリウムである、請求項6に記載の組成物。
- 緩衝マトリクスが、0から最大10体積パーセントの血餅溶解血漿を含有する、請求項1〜7のいずれか1項に記載の組成物。
- 緩衝マトリクスが、最大5体積パーセントの血餅溶解血漿を含有する、請求項8に記載の組成物。
- D−ダイマーの測定のための試験手順のコントロール又は検定のための、請求項1〜9のいずれか1項に記載のD−ダイマー含有組成物の使用。
- モノクローナル抗D−ダイマー抗体8D3を使用する、D−ダイマーの測定のための抗体を基にした試験手順のコントロール又は検定のための、請求項10に記載の使用。
- D−ダイマーを含有する請求項1に記載の組成物の製造のための方法であって、D−ダイマー溶液が緩衝化フィブリノゲン水溶液と混合される方法。
- 混合の後、組成物が限定期間の間30〜50℃でインキュベートされる、請求項12に記載の方法。
- 混合の後、組成物が限定期間の間37℃でインキュベートされる、請求項12に記載の方法。
- 混合の後に組成物が30〜50℃で4時間〜7日間インキュベートされる、請求項12に記載の方法。
- 混合の後に組成物が30〜50℃で12時間〜3日間インキュベートされる、請求項12に記載の方法。
- D−ダイマーを含有する緩衝マトリクスで構成される組成物の安定化のための、ヒト又は動物起源のフィブリノゲンの使用であって、組成物をフィブリノゲンと混合する工程、および混合の後、組成物を限定期間の間30〜50℃でインキュベートする工程を含む、使用。
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DE102007026153A DE102007026153A1 (de) | 2007-06-04 | 2007-06-04 | Stabile D-Dimer Flüssigzubereitung |
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CN103197083B (zh) * | 2013-03-20 | 2015-10-28 | 上海太阳生物技术有限公司 | D-二聚体质控品及其制备方法 |
CN107677839B (zh) * | 2017-09-20 | 2020-11-17 | 北京众驰伟业科技发展有限公司 | 一种d-二聚体和fdp复合质控品的制备方法 |
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JP3889084B2 (ja) * | 1996-05-15 | 2007-03-07 | 株式会社三菱化学ヤトロン | 新規なモノクローナル抗体並びにe−Dダイマー及びe−DD/E複合体の免疫学的測定法 |
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JP4471867B2 (ja) * | 2005-02-25 | 2010-06-02 | シスメックス株式会社 | Dダイマー測定用標準物質 |
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US8071723B2 (en) | 2011-12-06 |
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