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    Sustained release drug carrier
    1.
    发明授权
    Sustained release drug carrier 有权
    持续释放药物载体

    公开(公告)号：US07816316B2

    公开(公告)日：2010-10-19

    申请号：US10536031

    申请日：2003-11-21

    申请人： Sei Kwang Hahn ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

    发明人： Sei Kwang Hahn ,  Teruo Nakamura ,  Tsuyoshi Shimoboji

    IPC分类号： A61K38/02 ,  A61K31/728

    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。

    Crosslinked polysaccharide microparticles and method for their preparation
    2.
    发明授权
    Crosslinked polysaccharide microparticles and method for their preparation 有权
    交联多糖微粒及其制备方法

    公开(公告)号：US08575332B2

    公开(公告)日：2013-11-05

    申请号：US10579032

    申请日：2004-11-15

    申请人： Sei Kwang Hahn ,  Tsuyoshi Shimoboji

    发明人： Sei Kwang Hahn ,  Tsuyoshi Shimoboji

    IPC分类号： C08B37/00 ,  A61K9/50 ,  A61K9/62

    CPC分类号： A61K9/1652 ,  A61K9/0019 ,  A61K9/0024 ,  A61K9/1694 ,  C08B37/00 ,  C08B37/0072 ,  C08J3/12 ,  C08J3/24 ,  C08J2305/08

    摘要： The present invention provides long-acting sustained-release formulations of drugs such as proteins or peptides, which are injectable, completely biodegradable and safe, as well as ensuring efficient encapsulation of the drugs such as proteins or peptides without inhibiting their biological activity. It is possible to achieve injectable sustained-release formulations that ensure efficient encapsulation and long-term sustained release of drugs such as proteins or peptides while retaining their biological activity, when a solution containing a drug and a polysaccharide derivative such as hyaluronic acid having a crosslinkable functional group(s) or a salt thereof is dehydrated in microparticulate form starting from a dilute state, where crosslinking proceeds slowly, to reach a concentration which facilitates crosslinking, to thereby cause crosslinking reaction during concentration, so that the drug is encapsulated into the crosslinked polysaccharide to give drug-carrying microparticles.

    摘要翻译： 本发明提供了可注射，完全可生物降解和安全的药物（例如蛋白质或肽）的长效缓释制剂，以及确保药物如蛋白质或肽的有效包封而不抑制其生物学活性。 当含有药物和多糖衍生物如具有交联性的透明质酸的溶液时，可以实现可注射的持续释放制剂，其确保药物如蛋白质或肽的药物的有效包封和长期持续释放，同时保持其生物学活性 官能团或其盐以稀释状态从微细状态脱水，其中交联缓慢进行以达到促进交联的浓度，从而在浓缩期间引起交联反应，使得药物被包封到交联的 多糖以产生载药微粒。

    Process for producing water-soluble hyaluronic acid modification
    3.
    发明申请
    Process for producing water-soluble hyaluronic acid modification 有权
    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。

    Sustained release drug carrier
    4.
    发明申请
    Sustained release drug carrier 有权
    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。

    Hyaluronic acid modification products and drug carriers using them
    5.
    发明授权
    Hyaluronic acid modification products and drug carriers using them 有权
    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。

    CONJUGATE OF WATER-SOLUBLE HYALURONIC ACID MODIFICATION PRODUCT WITH GLP-A ANALOGUE
    7.
    发明申请
    CONJUGATE OF WATER-SOLUBLE HYALURONIC ACID MODIFICATION PRODUCT WITH GLP-A ANALOGUE 审中-公开
    具有GLP-A类似物的水溶性羟尿酸改性产品的结合

    公开(公告)号：US20090082266A1

    公开(公告)日：2009-03-26

    申请号：US11908278

    申请日：2006-03-08

    申请人： Teruo Nakamura ,  Tatsuya Kato ,  Hideyuki Togawa ,  Kenji Yasugi ,  Hiroko Konishi ,  Yasuo Sekimori ,  Tsuyoshi Shimoboji

    发明人： Teruo Nakamura ,  Tatsuya Kato ,  Hideyuki Togawa ,  Kenji Yasugi ,  Hiroko Konishi ,  Yasuo Sekimori ,  Tsuyoshi Shimoboji

    IPC分类号： A61K38/17 ,  A61P3/00

    CPC分类号： C07K14/605 ,  A61K47/61 ,  C08B37/0072

    摘要： To provide a GLP-1 analogue long-acting prophylactic or therapeutic agent for diabetes, diabetic complications and/or obesity due to diabetes which provides an extended half-life of a GLP-1 analogue in the blood to prevent frequent administration, and is biodegradable and safe.The present invention provides a conjugate obtained by binding, to a GLP-1 analogue into which a mercapto group is incorporated, water soluble hyaluronic acid modification product obtained by incorporating a substituent via an amide bond to the carboxyl group of glucuronic acid portion of hyaluronic acid as a derivative thereof, using a specific condensing agent in an aprotic polar solvent; and a prophylactic or therapeutic agent having a durable blood glucose lowering effect for diabetes, diabetic complications or obesity.

    摘要翻译： 提供GLP-1类似物长效预防或治疗糖尿病，由于糖尿病导致的糖尿病并发症和/或肥胖症，其提供血液中GLP-1类似物的延长半衰期以防止频繁施用，并且是可生物降解的 安全。 本发明提供了通过与其中引入巯基的GLP-1类似物结合获得的缀合物，其通过将酰胺键引入到透明质酸的葡萄糖醛酸部分的羧基而获得的水溶性透明质酸改性产物 作为其衍生物，在非质子极性溶剂中使用特定的缩合剂; 以及对糖尿病，糖尿病并发症或肥胖具有持久的血糖降低作用的预防或治疗剂。

    Process for producing water-soluble hyaluronic acid modification
    8.
    发明授权
    Process for producing water-soluble hyaluronic acid modification 有权
    生产水溶性透明质酸改性方法

    公开(公告)号：US08143391B2

    公开(公告)日：2012-03-27

    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： C07H1/00 ,  C08B37/08

    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 ratio 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 ratio 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，在引发比为5摩尔％以上的下限，使用BOP缩合剂在非质子传递极性溶剂中; 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比例，能够极长的药物持续释放的透明质酸凝胶。