JPH11512721A - 炎症反応の軽減のためのヘパリナーゼの使用 - Google Patents
炎症反応の軽減のためのヘパリナーゼの使用Info
- Publication number
- JPH11512721A JPH11512721A JP9513723A JP51372397A JPH11512721A JP H11512721 A JPH11512721 A JP H11512721A JP 9513723 A JP9513723 A JP 9513723A JP 51372397 A JP51372397 A JP 51372397A JP H11512721 A JPH11512721 A JP H11512721A
- Authority
- JP
- Japan
- Prior art keywords
- heparinase
- heparin
- enzyme
- endothelium
- inflammatory response
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.患者の組織における局所的炎症反応を軽減する方法であって、前記患者にヘ パリナーゼ酵素を前記局所的炎症反応を軽減するのに十分な有効量を投与するこ とを特徴とする方法。 2.前記ヘパリナーゼ酵素の前記投与により、ヘパリンおよびヘパラン硫酸を前 記組織の内皮細胞表面および細胞外基質から除去および消化することを特徴とす る請求項1に記載の方法。 3.前記ヘパリナーゼ酵素の前記投与により、内皮細胞表面および細胞外基質に 隣接する組織における白血球蓄積を軽減することを特徴とする請求項1に記載の 方法。 4.前記ヘパリナーゼ酵素の前記投与により、固定化ケモカインを放出し、さら に内皮に固定したケモカインを破壊して白血球の管外遊走を阻止することを特徴 とする請求項1に記載の方法。 5.前記ヘパリナーゼ酵素の前記投与により、白血球の内皮上の回転を阻止する ことを特徴とする請求項1に記載の方法。 6.フラボバクテリウム ヘパリナム(Flavobacterium heparinum)において、組 換えヌクレオチド配列により前記ヘパリナーゼ酵素を過剰発現することを特徴と する請求項1に記載の方法。 7.天然にはヘパリナーゼ酵素の発現が起こらない微生物において、組換えヌク レオチド配列により前記ヘパリナーゼ酵素を発現することを特徴とする請求項1 に記載の方法。 8.患者の組織の局所的炎症反応を軽減する方法であって、活性化内皮細胞に結 合するリガンドと、前記組織における前記局所的炎症反応を減らすのに十分な量 のヘパリナーゼ酵素とを含む融合蛋白質を前記患者に投与することをことを特徴 とする方法。 9.前記融合蛋白質が遺伝子工学的手法によって作られることを特徴とする請求 項8に記載の方法。 10.ヘパリナーゼ酵素と薬剤学的または獣医学的に許容可能な担体とを共に含 むことを特徴とする請求項8に記載の方法。 11.活性化内皮に結合するリガンドと、ヘパリナーゼ酵素とを含む融合分子を 含むことを特徴とする医薬組成物。 12.前記リガンド結合ドメインが、サイトカイン、抗体、インテグリンおよび セレクチンからなる群から選ばれることを特徴とする請求項11に記載の医薬組 成物。 13.前記リガンド結合ドメインが、前記サイトカイン、抗体、インテグリンお よびセレクチンのフラグメントであることを特徴とする請求項11に記載の医薬 組成物。 14.前記フラグメントが、サイトカイン受容体結合ドメイン、Fabフラグメ ント、抗体可変部、インテグリンI−ドメイン、およびセレクチンドメインから なる群から選ばれることを特徴とする請求項11に記載の医薬組成物。 15.前記担体がリポソーム、リポスフェア、プロテオソーム、ミクロスフェア 、マイクロカプセル、および生体内分解性ポリマーマトリックスからなる群から 選ばれることを特徴とする請求項10または11に記載の医薬組成物。 16.患者の組織における局所的炎症反応を軽減する治療用薬剤の調製における ヘパリナーゼ酵素の使用。 17.患者の組織における局所的炎症反応を軽減する治療用の、活性化内皮細胞 に結合するリガンドとヘパリナーゼ酵素とを含んでなる融合蛋白質を含むことを 特徴とする薬剤の調製におけるヘパリナーゼ酵素の使用。
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US462295P | 1995-09-29 | 1995-09-29 | |
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US08/722,659 US20010006635A1 (en) | 1995-09-29 | 1996-09-27 | Use of heparinase to decrease inflammatory responses |
PCT/US1996/015593 WO1997011684A1 (en) | 1995-09-29 | 1996-09-27 | Use of heparinases to decrease inflammatory responses |
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US (3) | US20010006635A1 (ja) |
EP (2) | EP1552846A3 (ja) |
JP (1) | JP3713276B2 (ja) |
AT (1) | ATE273020T1 (ja) |
AU (1) | AU703394B2 (ja) |
CA (1) | CA2233343A1 (ja) |
DE (1) | DE69633127T2 (ja) |
DK (1) | DK0852491T3 (ja) |
ES (1) | ES2227611T3 (ja) |
PT (1) | PT852491E (ja) |
WO (1) | WO1997011684A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007519755A (ja) * | 2004-01-30 | 2007-07-19 | エモリー ユニバーシティー | 神経再生を促進する材料および方法 |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6153187A (en) * | 1997-09-02 | 2000-11-28 | Insight Strategy & Marketing Ltd. | Use of glycosaminoglycans degrading enzymes for management of airway associated diseases |
CA2242693C (en) * | 1997-09-04 | 2002-09-17 | Becton, Dickinson And Company | Additive formulation and method of use thereof |
WO1999043830A2 (en) | 1998-02-24 | 1999-09-02 | Pharmacia & Upjohn Company | Human platelet heparanase polypeptides, polynucleotide molecules that encode them, and methods for the identification of compounds that alter heparanase activity |
US7056504B1 (en) | 1998-08-27 | 2006-06-06 | Massachusetts Institute Of Technology | Rationally designed heparinases derived from heparinase I and II |
EP1010762A1 (en) * | 1998-12-02 | 2000-06-21 | Aventis Behring Gesellschaft mit beschränkter Haftung | DNA constructs of blood clotting factors and P-Selectin |
EP1026250A1 (en) * | 1998-12-02 | 2000-08-09 | Aventis Behring GmbH | DNA-constructs of blood clotting factors and P-selectin |
CA2393855A1 (en) | 1999-12-22 | 2001-06-28 | Oxford Glycosciences (Uk) Ltd. | Homologues of human heparanase and splice variants thereof |
AU4351201A (en) * | 2000-03-08 | 2001-09-17 | Massachusetts Inst Technology | Heparinase iii and uses thereof |
WO2002032406A2 (en) | 2000-10-18 | 2002-04-25 | Massachusetts Institute Of Technology | Methods and products related to pulmonary delivery of polysaccharides |
ES2300439T3 (es) * | 2001-04-30 | 2008-06-16 | Zystor Therapeutics , Inc. | Reconocimiento subcelular de proteinas terapeuticas. |
US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
US7629309B2 (en) * | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
US20040005309A1 (en) * | 2002-05-29 | 2004-01-08 | Symbiontics, Inc. | Targeted therapeutic proteins |
US20030072761A1 (en) * | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
DE602005020745D1 (de) * | 2004-02-10 | 2010-06-02 | Zystor Therapeutics Inc | Saure alpha-glukosidase und fragmente davon |
CN1312183C (zh) * | 2004-05-19 | 2007-04-25 | 清华大学 | 一种肝素酶i融合蛋白及其编码基因与表达方法 |
CN100344769C (zh) * | 2005-08-04 | 2007-10-24 | 清华大学 | 一种制备低分子量肝素的方法 |
US7691612B2 (en) | 2005-11-03 | 2010-04-06 | Momenta Pharmaceuticals, Inc. | Heparan sulfate glycosaminoglycan lyase and uses thereof |
US7767420B2 (en) | 2005-11-03 | 2010-08-03 | Momenta Pharmaceuticals, Inc. | Heparan sulfate glycosaminoglycan lyase and uses thereof |
US7691613B2 (en) | 2006-11-03 | 2010-04-06 | Momenta Pharmaceuticals, Inc. | Glycosaminoglycan lyase IV and uses thereof |
EP2099523A2 (en) * | 2006-11-13 | 2009-09-16 | ZyStor Therapeutics , Inc. | Methods for treating pompe disease |
ES2830350T3 (es) | 2008-05-07 | 2021-06-03 | Biomarin Pharm Inc | Péptidos de dirección lisosómica y usos de los mismos |
ES2569514T3 (es) | 2009-06-17 | 2016-05-11 | Biomarin Pharmaceutical Inc. | Formulaciones para enzimas lisosómicas |
JP6293796B2 (ja) * | 2013-02-28 | 2018-03-14 | 花王株式会社 | 半永久的直毛化のための組成物及びプロセス |
WO2018165656A1 (en) | 2017-03-10 | 2018-09-13 | The University Of North Carolina At Chapel Hill | Short-acting heparin-based anticoagulant compounds and methods |
US11993627B2 (en) | 2017-07-03 | 2024-05-28 | The University Of North Carolina At Chapel Hill | Enzymatic synthesis of homogeneous chondroitin sulfate oligosaccharides |
CN111601603A (zh) | 2017-11-03 | 2020-08-28 | 北卡罗来纳大学查珀尔希尔分校 | 具有抗炎活性的硫酸化寡糖 |
CN112437667B (zh) | 2018-06-20 | 2024-05-28 | 北卡罗来纳大学查珀尔希尔分校 | 细胞保护方法和组合物 |
EP4041251A4 (en) * | 2019-11-13 | 2023-11-29 | The University of North Carolina at Chapel Hill | EFFECT OF HEPARAN SULFATE OLIGOSACCHARIDES (HS) IN ISCHEMIC REPERFUSION INJURY OF THE LIVER |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB941664A (en) * | 1959-02-19 | 1963-11-13 | Henry Thompson Stanton Jr | Buccal or sublingual tablet containing carbohydra e enzyme for controlling inflammation |
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
IL85145A (en) * | 1987-01-23 | 1994-08-26 | Univ Australian | Anti-metastatic pharmacological or veterinary preparations containing modified herpin with reduced anticoagulant activity |
US5169772A (en) * | 1988-06-06 | 1992-12-08 | Massachusetts Institute Of Technology | Large scale method for purification of high purity heparinase from flavobacterium heparinum |
CA2065744A1 (en) | 1989-08-23 | 1991-02-24 | Zvi Fuks | Wound healing preparations containing heparanase |
US5099855A (en) | 1989-11-09 | 1992-03-31 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University | Methods of and apparatus for monitoring respiration and conductive gel used therewith |
WO1992003473A1 (en) * | 1990-08-27 | 1992-03-05 | Cetus Corporation | Cd18 peptide medicaments for the treatment of disease |
US5270197A (en) | 1990-12-20 | 1993-12-14 | The Children's Medical Center Corporation | Cells expressing a substantial number of surface high affinity HBGF receptors but relatively few low affinity HBGF binding sites and system for assaying binding to HBGF receptor |
US5714376A (en) | 1991-10-23 | 1998-02-03 | Massachusetts Institute Of Technology | Heparinase gene from flavobacterium heparinum |
DK75593D0 (ja) | 1993-06-25 | 1993-06-25 | Novo Nordisk As | |
CA2176934A1 (en) * | 1993-11-17 | 1995-05-26 | Ramnath Sasisekharan | Method for inhibiting angiogenesis using heparinase |
US5997863A (en) * | 1994-07-08 | 1999-12-07 | Ibex Technologies R And D, Inc. | Attenuation of wound healing processes |
-
1996
- 1996-09-27 CA CA002233343A patent/CA2233343A1/en not_active Abandoned
- 1996-09-27 EP EP04076600A patent/EP1552846A3/en not_active Withdrawn
- 1996-09-27 PT PT96936052T patent/PT852491E/pt unknown
- 1996-09-27 EP EP96936052A patent/EP0852491B1/en not_active Expired - Lifetime
- 1996-09-27 AU AU73791/96A patent/AU703394B2/en not_active Ceased
- 1996-09-27 AT AT96936052T patent/ATE273020T1/de not_active IP Right Cessation
- 1996-09-27 JP JP51372397A patent/JP3713276B2/ja not_active Expired - Fee Related
- 1996-09-27 ES ES96936052T patent/ES2227611T3/es not_active Expired - Lifetime
- 1996-09-27 DK DK96936052T patent/DK0852491T3/da active
- 1996-09-27 US US08/722,659 patent/US20010006635A1/en not_active Abandoned
- 1996-09-27 DE DE69633127T patent/DE69633127T2/de not_active Expired - Fee Related
- 1996-09-27 WO PCT/US1996/015593 patent/WO1997011684A1/en active IP Right Grant
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2005
- 2005-05-02 US US11/118,477 patent/US20050191288A1/en not_active Abandoned
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007519755A (ja) * | 2004-01-30 | 2007-07-19 | エモリー ユニバーシティー | 神経再生を促進する材料および方法 |
Also Published As
Publication number | Publication date |
---|---|
EP0852491A4 (en) | 2002-08-07 |
ES2227611T3 (es) | 2005-04-01 |
US20010006635A1 (en) | 2001-07-05 |
PT852491E (pt) | 2004-11-30 |
EP1552846A3 (en) | 2008-05-07 |
WO1997011684A1 (en) | 1997-04-03 |
ATE273020T1 (de) | 2004-08-15 |
DE69633127T2 (de) | 2005-08-04 |
EP1552846A2 (en) | 2005-07-13 |
AU7379196A (en) | 1997-04-17 |
DK0852491T3 (da) | 2004-12-20 |
US20060140928A1 (en) | 2006-06-29 |
CA2233343A1 (en) | 1997-04-03 |
EP0852491B1 (en) | 2004-08-11 |
AU703394B2 (en) | 1999-03-25 |
US20050191288A1 (en) | 2005-09-01 |
US7264799B2 (en) | 2007-09-04 |
DE69633127D1 (de) | 2004-09-16 |
JP3713276B2 (ja) | 2005-11-09 |
EP0852491A1 (en) | 1998-07-15 |
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