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1. 发明授权

US07767806B2 Hyaluronic acid modification products and drug carriers using them 有权
标题翻译：透明质酸改性产品和使用它们的药物载体
公开(公告)号：US07767806B2
公开(公告)日：2010-08-03
申请号：US10571005
申请日：2004-09-08
申请人： Tai Hirakura , Teruo Nakamura , Tsuyoshi Shimoboji
发明人： Tai Hirakura , Teruo Nakamura , Tsuyoshi Shimoboji
IPC分类号： C07H5/04 , C07H1/00 , A61K31/728
CPC分类号： A61K9/5153 , A61K9/5161 , C08B37/0072 , C08G63/912
摘要： A hyaluronic acid modification product includes a polymer bonded to hyaluronic acid, the polymer being polylactic acid, polyglycolic acid or lactic acid-glycolic acid copolymer, providing a drug carrier which efficiently encapsulates low molecular weight drugs and provides sustained-release over a long term, control of blood residence, is well dispersible in an aqueous solution, and has excellent biocompatibility.
摘要翻译：透明质酸改性产品包括与透明质酸结合的聚合物，聚合物是聚乳酸，聚乙醇酸或乳酸 - 乙醇酸共聚物，提供有效地包封低分子量药物并长期持续释放的药物载体，血液停留的控制在水溶液中分散性良好，生物相容性优异。

2. 发明授权

US08759322B2 Hyaluronic acid derivative and pharmaceutical composition thereof 有权
标题翻译：透明质酸衍生物及其药物组合物
公开(公告)号：US08759322B2
公开(公告)日：2014-06-24
申请号：US13127582
申请日：2009-11-05
申请人： Kazunari Akiyoshi , Takashi Nakai , Tai Hirakura , Tsuyoshi Shimoboji
发明人： Kazunari Akiyoshi , Takashi Nakai , Tai Hirakura , Tsuyoshi Shimoboji
IPC分类号： A61K31/728 , A61K31/715 , C07H5/04 , C07H5/06
CPC分类号： A61K9/0019 , A61K38/00 , A61K47/36 , A61K47/61 , C08B37/0072 , C08J3/12 , C08J2305/08
摘要： The present invention provides a hydrophobic group-introduced hyaluronic acid derivative comprising at least one repeating unit represented by the formula (I): wherein R1, R2, R3, R4, Z, n, Ra, Y, and X1 are as defined in the specification.
摘要翻译：本发明提供了包含至少一个由式（I）表示的重复单元的疏水基导入的透明质酸衍生物：其中R1，R2，R3，R4，Z，n，Ra，Y和X1如规范。

3. 发明申请

US20130338352A1 DERIVATIVE OF HYALURONIC ACID MODIFIED WITH AMINO-CARBOXYLIC ACID 有权
标题翻译：用氨基羧酸改性羟丙酸的衍生物
公开(公告)号：US20130338352A1
公开(公告)日：2013-12-19
申请号：US14002919
申请日：2012-03-02
申请人： Tomoko Yasugi , Yoshihiro Tampo , Kenji Yasugi , Tai Hirakura , Tsuyoshi Shimoboji
发明人： Tomoko Yasugi , Yoshihiro Tampo , Kenji Yasugi , Tai Hirakura , Tsuyoshi Shimoboji
IPC分类号： C08B37/08
CPC分类号： C08B37/0072 , A61K31/728 , A61K47/61
摘要： The present invention provides a hyaluronic acid derivative comprising disaccharide units of Formula (I), and a hyaluronic acid derivative/drug conjugate wherein one or more drugs are conjugated to the hyaluronic acid derivative.
摘要翻译：本发明提供了包含式（I）的二糖单元和透明质酸衍生物/药物结合物的透明质酸衍生物，其中一种或多种药物与透明质酸衍生物缀合。

4. 发明申请

US20100204102A1 HYBRID GEL COMPRISING CHEMICALLY CROSSLINKED HYALURONIC ACID DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME 有权
标题翻译：混合凝胶包含化学交联的羟丙酸衍生物和包含其的药物组合物
公开(公告)号：US20100204102A1
公开(公告)日：2010-08-12
申请号：US12598498
申请日：2008-04-30
申请人： Kazunari Akiyoshi , Nobuyuki Morimoto , Tai Hirakura , Tsuyoshi Shimoboji
发明人： Kazunari Akiyoshi , Nobuyuki Morimoto , Tai Hirakura , Tsuyoshi Shimoboji
IPC分类号： A61K38/16 , A61K47/36 , A61K38/02 , A61P19/04 , A61K8/00
CPC分类号： A61K9/0014 , A61K9/06 , A61K9/08 , A61K47/36
摘要： The present invention provides a composition comprising a hyaluronic acid derivative having a crosslinking group(s) and a hydrophilic polysaccharide derivative having a hydrophobic group(s), wherein the hyaluronic acid derivative having a crosslinking group(s) is prepared by crosslinkage formation reaction in hyaluronic acid or a derivative thereof having a crosslinkable group(s) in the presence of the hydrophilic polysaccharide derivative wherein the hydrophilic polysaccharide derivative may have a crosslinkable group(s).
摘要翻译：本发明提供一种组合物，其含有具有交联基团的透明质酸衍生物和具有疏水性基团的亲水性多糖衍生物，其中，具有交联基团的透明质酸衍生物通过交联形成反应在亲水性多糖衍生物存在下具有交联性基团的透明质酸或其衍生物，其中亲水性多糖衍生物可以具有交联性基团。

5. 发明申请

US20090286724A1 AGGREGABLE GLP-1 ANALOGUE AND SUSTAINED-RELEASE PHARMACEUTICAL COMPOSITION 审中-公开
标题翻译：可累积的GLP-1类似物和持续释放的药物组合物
公开(公告)号：US20090286724A1
公开(公告)日：2009-11-19
申请号：US12067067
申请日：2006-10-26
申请人： Hiroko Konishi , Tomoyuki Igawa , Tsuyoshi Shimoboji , Tai Hirakura
发明人： Hiroko Konishi , Tomoyuki Igawa , Tsuyoshi Shimoboji , Tai Hirakura
IPC分类号： A61K38/26 , C07K14/605 , A61P3/10 , A61P3/04
CPC分类号： C07K14/605 , A61K38/00 , Y02A50/473
摘要： The present invention provides a GLP-1 analogue having a high association-aggregability or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition to be used for preventing or treating diabetes, hyperglycemia, a diabetic complication caused by diabetes or hyperglycemia, or obesity, using the same.
摘要翻译：本发明提供具有高缔合聚集性的GLP-1类似物或其药学上可接受的盐，以及用于预防或治疗糖尿病，高血糖症，由糖尿病或高血糖引起的糖尿病并发症或肥胖的药物组合物，其使用一样。

6. 发明授权

US09243077B2 Derivative of hyaluronic acid modified with amino-carboxylic acid 有权
标题翻译：用氨基羧酸改性的透明质酸衍生物
公开(公告)号：US09243077B2
公开(公告)日：2016-01-26
申请号：US14002919
申请日：2012-03-02
申请人： Tomoko Yasugi , Yoshihiro Tampo , Kenji Yasugi , Tai Hirakura , Tsuyoshi Shimoboji
发明人： Tomoko Yasugi , Yoshihiro Tampo , Kenji Yasugi , Tai Hirakura , Tsuyoshi Shimoboji
IPC分类号： C08B37/08 , A61K31/728 , A61K47/48
CPC分类号： C08B37/0072 , A61K31/728 , A61K47/61
摘要： The present invention provides a hyaluronic acid derivative comprising disaccharide units of Formula (I), and a hyaluronic acid derivative/drug conjugate wherein one or more drugs are conjugated to the hyaluronic acid derivative.
摘要翻译：本发明提供了包含式（I）的二糖单元和透明质酸衍生物/药物结合物的透明质酸衍生物，其中一种或多种药物与透明质酸衍生物缀合。

7. 发明授权

US08987230B2 Hybrid gel comprising chemically crosslinked hyaluronic acid derivative and pharmaceutical composition comprising the same 有权
标题翻译：包含化学交联的透明质酸衍生物和包含其的药物组合物的混合凝胶
公开(公告)号：US08987230B2
公开(公告)日：2015-03-24
申请号：US12598498
申请日：2008-04-30
申请人： Kazunari Akiyoshi , Nobuyuki Morimoto , Tai Hirakura , Tsuyoshi Shimoboji
发明人： Kazunari Akiyoshi , Nobuyuki Morimoto , Tai Hirakura , Tsuyoshi Shimoboji
IPC分类号： A61K31/715 , A61K31/728 , A61K31/719 , A61K31/718 , A61K31/721 , A61K31/722 , A61K9/00 , A61K9/06 , A61K9/08 , A61K47/36
CPC分类号： A61K9/0014 , A61K9/06 , A61K9/08 , A61K47/36
摘要： The present invention provides a composition comprising a hyaluronic acid derivative having a crosslinking group(s) and a hydrophilic polysaccharide derivative having a hydrophobic group(s), wherein the hyaluronic acid derivative having a crosslinking group(s) is prepared by crosslinkage formation reaction in hyaluronic acid or a derivative thereof having a crosslinkable group(s) in the presence of the hydrophilic polysaccharide derivative wherein the hydrophilic polysaccharide derivative may have a crosslinkable group(s).
摘要翻译：本发明提供一种组合物，其含有具有交联基团的透明质酸衍生物和具有疏水性基团的亲水性多糖衍生物，其中，具有交联基团的透明质酸衍生物通过交联形成反应在亲水性多糖衍生物存在下具有交联性基团的透明质酸或其衍生物，其中亲水性多糖衍生物可以具有交联性基团。

8. 发明申请

US20110212901A1 HYALURONIC ACID DERIVATIVE AND PHARMACEUTICAL COMPOSITION THEREOF 有权
标题翻译：羟丙酸衍生物及其药物组合物
公开(公告)号：US20110212901A1
公开(公告)日：2011-09-01
申请号：US13127582
申请日：2009-11-05
申请人： Kazunari Akiyoshi , Takashi Nakai , Tai Hirakura , Tsuyoshi Shimoboji
发明人： Kazunari Akiyoshi , Takashi Nakai , Tai Hirakura , Tsuyoshi Shimoboji
IPC分类号： A61K38/17 , C08B37/08
CPC分类号： A61K9/0019 , A61K38/00 , A61K47/36 , A61K47/61 , C08B37/0072 , C08J3/12 , C08J2305/08
摘要： The present invention provides a hydrophobic group-introduced hyaluronic acid derivative comprising at least one repeating unit represented by the formula (I): wherein R1, R2, R3, R4, Z, n, Ra, Y, and X1 are as defined in the specification.
摘要翻译：本发明提供了包含至少一个由式（I）表示的重复单元的疏水基导入的透明质酸衍生物：其中R1，R2，R3，R4，Z，n，Ra，Y和X1如规范。

9. 发明申请

US20090148534A1 Process for producing water-soluble hyaluronic acid modification 有权
标题翻译：生产水溶性透明质酸改性方法
公开(公告)号：US20090148534A1
公开(公告)日：2009-06-11
申请号：US11662087
申请日：2005-09-07
申请人： Kenji Yasugi , Teruo Nakamura , Tsuyoshi Shimoboji , Mika Sato
发明人： Kenji Yasugi , Teruo Nakamura , Tsuyoshi Shimoboji , Mika Sato
IPC分类号： A61K9/14 , C07H1/00 , C07H3/00
CPC分类号： C08B37/0072 , A61K47/61 , C08J3/075 , C08J3/122 , C08L5/08
摘要： The present invention provides a water-soluble modified HA practically used as a drug carrier and a production method thereof. The present invention provides: a water-soluble modified hyaluronic acid, the residence time in blood of which is elongated to a practical level, which is produced by introducing a substituent into the carboxy group of the glucuronic acid of hyaluronic acid or a derivative thereof, via an amide bond, at a lower limit of an introduction rate of 5 mole % or more, using a BOP condensing agent in an aprotic polar solvent; and a production method thereof. Moreover, by cross-linking the modified hyaluronic acid, the present invention provides a hyaluronic acid gel capable of extremely long drug sustained-release even at the same cross-linking functional group introduction rate as that of the conventionally known gel.
摘要翻译：本发明提供实际上用作药物载体的水溶性改性HA及其制备方法。本发明提供：通过将透明质酸的葡糖醛酸或其衍生物的羧基引入取代基而产生的水溶性改性透明质酸，其在血液中的停留时间延长到实用水平，通过酰胺键，在非极性极性溶剂中使用BOP缩合剂，在5摩尔％以上的引入速率的下限; 及其制造方法。此外，通过交联改性透明质酸，本发明提供即使以与常规已知凝胶相同的交联官能团引入速率也能够极长的药物持续释放的透明质酸凝胶。

10. 发明申请

US20060110458A1 Sustained release drug carrier 有权
标题翻译：持续释放药物载体
公开(公告)号：US20060110458A1
公开(公告)日：2006-05-25
申请号：US10536031
申请日：2003-11-21
申请人： Sei Hahn , Teruo Nakamura , Tsuyoshi Shimoboji
发明人： Sei Hahn , Teruo Nakamura , Tsuyoshi Shimoboji
IPC分类号： A61K31/728 , C08B37/00 , A61K9/14
CPC分类号： A61K9/06 , A61K9/0019 , A61K47/36 , C08B37/0072
摘要： The present invention aims to provide completely biodegradable and biocompatible sustained-release carriers for proteins or peptides, which allow encapsulation of the proteins or peptides at high encapsulation rates without inhibiting their biological activity. The present invention provides a method for preparing a sustained-release carrier, wherein in a solution in the presence of a protein or a peptide, a hyaluronic acid derivative having an unsaturated bond(s) or a mercapto group(s) introduced into hyaluronic acid is chemically crosslinked with a mercapto group-containing compound or an unsaturated bond-containing compound, respectively, to give a hydrogel. The method of the present invention enables efficient encapsulation of proteins or peptides while retaining their biological activity.
摘要翻译：本发明旨在提供用于蛋白质或肽的完全可生物降解和生物相容的缓释载体，其允许以高包封率封装蛋白质或肽而不抑制其生物学活性。本发明提供了一种制备缓释载体的方法，其中在蛋白质或肽存在下的溶液中，将具有引入透明质酸的不饱和键或巯基的透明质酸衍生物分别与含巯基的化合物或含不饱和键的化合物进行化学交联，得到水凝胶。本发明的方法能够有效地包封蛋白质或肽，同时保持其生物活性。

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