JP6258868B2 - 止血創傷被覆材 - Google Patents
止血創傷被覆材 Download PDFInfo
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- JP6258868B2 JP6258868B2 JP2014555315A JP2014555315A JP6258868B2 JP 6258868 B2 JP6258868 B2 JP 6258868B2 JP 2014555315 A JP2014555315 A JP 2014555315A JP 2014555315 A JP2014555315 A JP 2014555315A JP 6258868 B2 JP6258868 B2 JP 6258868B2
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- wound dressing
- fibrinogen
- peptide
- coating material
- hemostatic
- Prior art date
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Classifications
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- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0015—Medicaments; Biocides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
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Description
フィブリノーゲン結合ペプチドのアルブミン担体への結合
本実施例は、ポリエチレングリコール(PEG)リンカーによってマレイミド基(Mal)に連結する配列GPRPGのフィブリノーゲン結合ペプチドのアルブミン担体への結合を説明する。結果として得られる生成物は、「PeproStat」と称される。
生成物プロファイル
ゼラチンパッド上で予浸されたPeproStatの止血活性試験
ヘパリン処置されたウサギモデルを使用してPeproStatの止血活性を判定した。しかしながら、このモデルを使用する前に、生成物がウサギにおいて有効であること、および特に、PeproStat(GPRP−)のフィブリノーゲン結合配列がウサギフィブリノーゲンに結合することを判定することが重要であった。これはGPRPGペプチドをアルブミン微小粒子に結合することによって行われ、次いで、これをFITC標識化ウサギフィブリノーゲンとともにインキュベートした。次いで、粒子への蛍光フィブリノーゲン結合がFlow Cytometerを使用して測定され得る。この方法により、PeproStatのウサギフィブリノーゲンへの結合がヒトフィブリノーゲンのものに匹敵したことが示された。これは、トロンビンがフィブリノペプチドAをフィブリノーゲンから切断するときに曝露される関連するウサギおよびヒトフィブリノーゲン結合配列が同じであることを示す公開データを確証する。
0のスコア(すなわち出血なし)は、各時点において成功した止血として判断された。成功と見なされた34の処置(n=34羽のウサギ)の割合を各時点において算出した。結果は、図3bに示される。
ゼラチンパッド上でのPeproStatの凍結乾燥
パッドの吸収容量を判定するために、40cm2ゼラチンパッドを10mlの脱イオン水に浸した。すべての空気を排除するようにパッドをマッサージし、再度浸すことによって吸収度を最大化した後、2mlの水が残った。それにより、40cm2パッドの容量が8mlであったことを算出した。
結果は図4に示される。
レーヨン/ポリエステル多孔性被覆材上に浸されたPeproStatの止血活性
以下の血液インピーダンス法を使用して、ポリエステル/レーヨン混合物上に浸された5mg/mLの0.5mL PeproStatの止血活性を測定した。
図5に示される代表的な図において例示されるように、ガーゼを通過した血液の平均重量とPeproStatの和は、対照ガーゼ(n=3)を通過した0.695g±0.721gと比較して、0.009g±0.016g(n=3)であった。
固定化されるフィブリノーゲン結合ペプチドを有するゼラチン担体の止血性質
この実施例は、2つの異なる本発明の好ましい止血創傷被覆材の調製およびそれらの止血特性を説明する。両方の被覆材は、PEGリンカーを介して担体に共有結合的に固定化される複数のフィブリノーゲン結合ペプチドを有する複数のゼラチン担体を含む。この実施例において、ゼラチン担体(または顆粒)は、非コロイド多孔性被覆材料を提供する。
アミン残基を修飾する2−イミノチオランを使用してゼラチン顆粒をチオール化した。使用された方法は、Kommareddy S,Amiji M,2005,Bioconjugate Chem16:1423−1432のものであった。
2.2gのゼラチン顆粒を検量し、回転式撹拌機上で15分間、80mLの50mM MES緩衝剤、pH6.0中で水和した。625mgのシスタミン、350mgの1−エチル−3−(3−ジメチルアミノプロピル)カルボジイミド塩酸塩(EDC)、および130mgのN−ヒドロキシスクシンイミド(NHS)を検量し、水和した顆粒に添加した。この反応混合物を環境温度で2時間、回転式撹拌機上に放置し、次いで、2つの50mL管に分割した。次いで、この顆粒を洗浄し、4×40mL体積のMES緩衝剤を用いて500rpmで回転させた。200μLの1Mトリス(2−カルボキシエチル)ホスフィン(TCEP)ストックを各管に添加し、環境温度で10分間回転式撹拌機上に放置した。4体積のMESでの繰り返し洗浄に次いで、遊離−SHを判定するエルマンアッセイが続いた。
凍結乾燥機の棚を−36℃で平衡化し、ゼラチン顆粒を予め凍結した棚に配置し、270分間にわたって−20℃まで達する温度になる熱処理ステップに供した。一次乾燥は、20℃の温度までの同時の温度上昇を伴って、800mTorrから減圧する800分間にわたって達成された。試験前に凍結乾燥されたパッドをデシケーター内で保管した。
100mgの乾燥結合ゼラチン顆粒を3mlシリンジ中に充填し、次いで、シリンジコネクターを使用して、0.5mlトリス−緩衝生理食塩水(TBS)(0.02Mトリス、0.15M NaCl、pH7.2±0.2)を添加し、顆粒を懸濁した。500u/mlの0.5mlトロンビンまたは0.5ml TBSを100mg「ブランク」(非結合ゼラチン顆粒)に添加した。シリンジコネクターを使用して、TBSを別の3mlシリンジから各形成へ通過させ、それを懸濁した。次いで、シリンジ間でおよそ40回それを通過させることによって、各懸濁液を混合した。
結果
実施例6
溶液中で担体に固定化されるフィブリノーゲン結合ペプチドの安定性
Claims (22)
- 止血創傷被覆材であって、非コロイド多孔性被覆材料および前記非コロイド多孔性被覆材料に固定化される複数のフィブリノーゲン結合ペプチドを含み、各フィブリノーゲン結合ペプチドが、
前記ペプチドのアミノ末端にアミノ酸配列Gly−Pro−Arg−Xaa(配列番号1)(式中、Xaaは、Pro、Sar(サルコシン)、またはLeuである)を含み、
複数の担体が非コロイド多孔性被覆材料に固定され、複数のフィブリノーゲン結合ペプチドが各担体に共有結合的に固定されているか、又は、複数のフィブリノーゲン結合ペプチドが非コロイド性多孔性被覆材料に共有結合的に固定されている、止血創傷被覆材。 - 各フィブリノーゲン結合ペプチドが、非ペプチドスペーサーによって前記担体に共有結合的に固定化される、請求項1に記載の創傷被覆材。
- 前記非ペプチドスペーサーが、親水性ポリマーを含む、請求項2に記載の創傷被覆材。
- 前記親水性ポリマーが、ポリエチレングリコールを含む、請求項3に記載の創傷被覆材。
- 前記担体が、可溶性担体である、請求項1〜4のいずれか1項に記載の創傷被覆材。
- 各フィブリノーゲン結合ペプチドが、非ペプチドスペーサーによって前記非コロイド多孔性被覆材料に共有結合的に固定化される、請求項1に記載の創傷被覆材。
- 前記非ペプチドスペーサーが、親水性ポリマーを含む、請求項6に記載の創傷被覆材。
- 前記親水性ポリマーが、ポリエチレングリコールを含む、請求項7に記載の創傷被覆材。
- 前記非コロイド多孔性被覆材料が、シート、パッド、スポンジ、発泡材、フィルム、ガーゼ、メッシュ、または顆粒、もしくはビーズを含む、請求項1〜8のいずれか1項に記載の創傷被覆材。
- 前記非コロイド多孔性被覆材料が、顆粒を含み、前記顆粒の大半が、6μmを超える最大寸法を有する、請求項9に記載の創傷被覆材。
- 前記非コロイド多孔性被覆材料が、ゼラチン、綿、レーヨン、ポリエステル、コラーゲン、アルギン酸塩、または酸化セルロースを含む、請求項1〜10のいずれか1項に記載の創傷被覆材。
- 乾燥形態である、請求項1〜11のいずれか1項に記載の創傷被覆材。
- 凍結乾燥形態である、請求項1〜12のいずれか1項に記載の創傷被覆材。
- 前記フィブリノーゲン結合ペプチドが、それぞれ4〜60アミノ酸残基長である、請求項1〜13のいずれか1項に記載の創傷被覆材。
- 前記創傷被覆材を創傷に適用するための説明書とともにパッケージ化された、請求項1〜14のいずれか1項に記載の創傷被覆材。
- 出血を制御するための、請求項1〜14のいずれか1項に記載の創傷被覆材。
- 止血創傷被覆材の形成用キットであって、非コロイド多孔性被覆材料と、別々に、複数の担体および各担体に共有結合的に固定化される複数のフィブリノーゲン結合ペプチドを含む止血剤と、を含み、各フィブリノーゲン結合ペプチドが、前記ペプチドのアミノ末端にアミノ酸配列Gly−Pro−Arg−Xaa(配列番号1)(式中、Xaaは、Pro、Sar(サルコシン)、またはLeuである)を含む、止血創傷被覆材の形成用キット。
- 前記被覆材料を創傷に適用する前に、前記薬剤を前記非コロイド多孔性被覆材料に適用するための説明書をさらに含む、請求項17に記載のキット。
- 前記止血創傷被覆材を創傷に適用するための説明書をさらに含む、請求項17または18に記載のキット。
- 止血剤であって、複数の担体および各担体に共有結合的に固定化される複数のフィブリノーゲン結合ペプチドを含む止血剤であって、各フィブリノーゲン結合ペプチドが、
前記ペプチドのアミノ末端にアミノ酸配列Gly−Pro−Arg−Xaa(配列番号1)(式中、Xaaは、Pro、Sar(サルコシン)、またはLeuである)を含み、
前記薬剤が、前記被覆材料を創傷に適用する前に、前記薬剤を非コロイド多孔性被覆材料に適用するための説明書とともにパッケージ化される、止血剤。 - 止血創傷被覆材を作製する方法であって、複数のフィブリノーゲン結合ペプチドを非コロイド多孔性被覆材料に固定化することを含み、各フィブリノーゲン結合ペプチドが、
前記ペプチドのアミノ末端にアミノ酸配列Gly−Pro−Arg−Xaa(配列番号1)(式中、Xaaは、Pro、Sar(サルコシン)、またはLeuである)を含み、
複数の担体が非コロイド性多孔性被覆材料に固定され、複数のフィブリノーゲン結合ペプチドが各担体に共有結合的に固定されているか、又は、複数のフィブリノーゲン結合ペプチドが非コロイド性多孔性被覆材料に共有結合的に固定されている、方法。 - 止血創傷被覆材を作製する方法であって、止血剤を非コロイド多孔性被覆材料に適用することを含み、前記止血剤が、複数の担体および各担体に共有結合的に固定化される複数のフィブリノーゲン結合ペプチドを含み、各フィブリノーゲン結合ペプチドが、前記ペプチドのアミノ末端にアミノ酸配列Gly−Pro−Arg−Xaa(配列番号1)(式中、Xaaは、Pro、Sar(サルコシン)、またはLeuである)を含む、方法。
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Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0516091D0 (en) * | 2005-08-04 | 2005-09-14 | Haemostatix Ltd | Therapeutic agent |
GB0808376D0 (en) | 2008-05-08 | 2008-06-18 | Bristol Myers Squibb Co | Wound dressing |
GB0817796D0 (en) | 2008-09-29 | 2008-11-05 | Convatec Inc | wound dressing |
GB201020236D0 (en) | 2010-11-30 | 2011-01-12 | Convatec Technologies Inc | A composition for detecting biofilms on viable tissues |
JP5965409B2 (ja) | 2010-12-08 | 2016-08-03 | コンバテック・テクノロジーズ・インコーポレイテッドConvatec Technologies Inc | 創傷滲出液を評価するための統合システム |
JP6151186B2 (ja) | 2010-12-08 | 2017-06-21 | コンバテック・テクノロジーズ・インコーポレイテッドConvatec Technologies Inc | 創傷滲出液システム付属装置 |
GB201115182D0 (en) | 2011-09-02 | 2011-10-19 | Trio Healthcare Ltd | Skin contact material |
GB2497406A (en) | 2011-11-29 | 2013-06-12 | Webtec Converting Llc | Dressing with a perforated binder layer |
GB201120693D0 (en) | 2011-12-01 | 2012-01-11 | Convatec Technologies Inc | Wound dressing for use in vacuum therapy |
CA2895896A1 (en) | 2012-12-20 | 2014-06-26 | Convatec Technologies Inc. | Processing of chemically modified cellulosic fibres |
GB201400292D0 (en) * | 2014-01-08 | 2014-02-26 | Haemostatix Ltd | Peptide dendrimers and agents |
US12083245B2 (en) | 2014-10-02 | 2024-09-10 | Wake Forest University Health Sciences | Amniotic membrane powder and its use in wound healing and tissue engineering constructs |
GB201508024D0 (en) * | 2015-05-11 | 2015-06-24 | Haemostatix Ltd | Haemostatic compositions |
GB201508014D0 (en) * | 2015-05-11 | 2015-06-24 | Haemostatix Ltd | Haemostatic device |
GB201508020D0 (en) * | 2015-05-11 | 2015-06-24 | Haemostatix Ltd | Haemostatic material |
US20170152556A1 (en) * | 2015-06-08 | 2017-06-01 | The Procter & Gamble Company | Methods for identifying circadian rhythm-dependent cosmetic agents for skin care compositions |
MX2018002649A (es) * | 2015-09-01 | 2018-06-20 | Baxter Int | Material hemostatico. |
GB2543307B (en) * | 2015-10-14 | 2020-12-09 | Selentus Science Ltd | Haemostatic device |
EP3435941B1 (en) | 2016-03-30 | 2021-09-01 | ConvaTec Technologies Inc. | Detecting microbial infections in wounds |
BR112018070238A2 (pt) | 2016-03-30 | 2019-01-29 | Acib Gmbh | detecção de infecção microbiana em feridas |
KR20190028467A (ko) | 2016-07-08 | 2019-03-18 | 컨바텍 테크놀러지스 인크 | 체액 수집 장치 |
KR20190026858A (ko) | 2016-07-08 | 2019-03-13 | 컨바텍 테크놀러지스 인크 | 가요성 부압 시스템 |
ES2912094T3 (es) | 2016-07-08 | 2022-05-24 | Convatec Technologies Inc | Detección de flujo de fluidos |
CN106344960B (zh) * | 2016-09-20 | 2019-02-22 | 安徽思维特生物科技有限公司 | 利用微晶纤维素接枝改性胎牛皮胶原纤维制备的止血凝胶 |
IL256405A (en) * | 2017-12-19 | 2018-01-31 | Omrix Biopharmaceuticals Ltd | Wound bandage and method for its production |
GB2571080A (en) * | 2018-02-14 | 2019-08-21 | Medtrade Products Ltd | Haemostatic material |
JP7511585B2 (ja) | 2019-06-03 | 2024-07-05 | コンバテック リミティド | 病原体を破壊して封じ込めるための方法およびデバイス |
CN110448719B (zh) * | 2019-06-28 | 2020-05-22 | 浙江大学 | 一种促进凝血的丝素-多肽电纺膜及其制备方法 |
US11771819B2 (en) | 2019-12-27 | 2023-10-03 | Convatec Limited | Low profile filter devices suitable for use in negative pressure wound therapy systems |
US11331221B2 (en) | 2019-12-27 | 2022-05-17 | Convatec Limited | Negative pressure wound dressing |
GB2596525A (en) * | 2020-06-26 | 2022-01-05 | Fujifilm Corp | Modified gelatins |
CN112206307B (zh) * | 2020-09-15 | 2023-12-05 | 广州领晟医疗科技有限公司 | 一种可注射的温敏型水凝胶及其制备方法与应用 |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE13810T1 (de) | 1981-06-25 | 1985-07-15 | Serapharm Gmbh & Co Kg | Angereichertes plasmaderivat zur unterstuetzung von wundverschluss und wundabdeckung. |
GB9107628D0 (en) | 1991-04-10 | 1991-05-29 | Moonbrook Limited | Preparation of diagnostic agents |
WO1993023997A1 (en) | 1992-05-29 | 1993-12-09 | The University Of North Carolina At Chapel Hill | Pharmaceutically acceptable fixed-dried human blood platelets |
WO1997044015A1 (en) | 1996-05-17 | 1997-11-27 | Andaris Limited | Microparticles and their use in wound therapy |
JP2001504813A (ja) | 1996-10-21 | 2001-04-10 | クウォドラント、ヘルスケアー、(ユーケー)、リミテッド | 代用血小板、及びそれらの製造に適した抱合法 |
US6891077B2 (en) | 2001-07-25 | 2005-05-10 | The United States Of America As Represented By The Secretary Of The Army | Fibrinogen bandages and arterial bleeding models and methods of making and using thereof |
WO2003088990A1 (en) * | 2002-04-15 | 2003-10-30 | American National Red Cross | Plasma protein-binding ligands |
US20040101546A1 (en) * | 2002-11-26 | 2004-05-27 | Gorman Anne Jessica | Hemostatic wound dressing containing aldehyde-modified polysaccharide and hemostatic agents |
GB2410687A (en) | 2002-11-20 | 2005-08-10 | Univ Bar Ilan | Biological glue based on thrombin-conjugated nanoparticles |
DE10323794A1 (de) | 2003-05-23 | 2004-12-09 | Dr. Suwelack Skin & Health Care Ag | Verfahren zur Herstellung von Alginat-haltigen porösen Formkörpern |
US20050123588A1 (en) | 2003-06-16 | 2005-06-09 | Zhu Yong H. | Deployable multifunctional hemostatic agent |
US7186684B2 (en) | 2003-08-07 | 2007-03-06 | Ethicon, Inc. | Hemostatic device containing a protein precipitate |
US7927626B2 (en) | 2003-08-07 | 2011-04-19 | Ethicon, Inc. | Process of making flowable hemostatic compositions and devices containing such compositions |
GB0323378D0 (en) * | 2003-10-07 | 2003-11-05 | Univ Leicester | Therapeutic agent |
JP2008507362A (ja) | 2004-07-22 | 2008-03-13 | ヘモ ナノサイエンス リミテッド ライアビリティ カンパニー | 過剰な出血を処置するための組成物および方法 |
US9358318B2 (en) | 2004-10-20 | 2016-06-07 | Ethicon, Inc. | Method of making a reinforced absorbable multilayered hemostatic wound dressing |
GB0516091D0 (en) * | 2005-08-04 | 2005-09-14 | Haemostatix Ltd | Therapeutic agent |
GB0623607D0 (en) * | 2006-11-27 | 2007-01-03 | Haemostatix Ltd | Tissue adhesive |
CN101854960B (zh) * | 2006-12-15 | 2014-06-25 | 生命连结有限公司 | 明胶-转谷氨酰胺酶止血敷料和密封材料 |
EP2183280B1 (en) * | 2007-08-01 | 2011-10-26 | Ethicon, Inc. | Collagen-related peptides and uses thereof |
US8512740B2 (en) | 2008-03-26 | 2013-08-20 | Baxter International Inc. | Fibrin foam and process for making |
US20100021527A1 (en) | 2008-07-25 | 2010-01-28 | Chunlin Yang | Collagen-related peptides and uses thereof and hemostatic foam substrates |
WO2011006069A1 (en) | 2009-07-09 | 2011-01-13 | Georgia Tech Research Corporation | Peptides for binding fibrinogen and fibrin |
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