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    SINGLE-STEP FUNCTIONALIZATION AND CROSS-LINKING OF HYALURONIC ACID
    53.
    发明申请
    SINGLE-STEP FUNCTIONALIZATION AND CROSS-LINKING OF HYALURONIC ACID 审中-公开
    羟丙酸的单步功能化和交联

    公开(公告)号：US20160237177A1

    公开(公告)日：2016-08-18

    申请号：US15024647

    申请日：2014-09-30

    申请人： GALDERMA S.A.

    发明人： Jean-Guy BOITEAU

    IPC分类号： C08B37/08 ,  A61L27/20 ,  A61L27/50 ,  A61K49/00

    CPC分类号： C08B37/0072 ,  A61K8/735 ,  A61K49/0054 ,  A61K2800/91 ,  A61L27/20 ,  A61L27/50 ,  A61L27/52 ,  A61L27/54 ,  A61L2300/442 ,  A61L2400/06 ,  A61Q19/00 ,  C08L5/08

    摘要： A process for manufacturing a cross-linked hyaluronic acid (HA) containing a functionalizing group including the step of reacting HA with a mixture of: (i) a first cross-linking agent selected from the group of bifunctional epoxides and polyfunctional epoxides, and (ii) a functionalized agent of a functionalizing group coupled via a 1,2,3-triazole linkage to a second cross-linking agent selected from the group of bifunctional epoxides and polyfunctional epoxides, to obtain a cross-linked HA containing the functionalizing group. The process provides a cross-linked hyaluronic acid (HA) containing a functionalizing group. The process utilizes a functionalized agent of a functionalizing group coupled via a 1,2,3-triazole linkage to a cross-linking agent.

    摘要翻译： 一种制备含有官能团的交联透明质酸（HA）的方法，包括使HA与以下混合物反应的步骤：（i）选自双功能环氧化物和多官能环氧化物的第一交联剂和（ ii）通过1,2,3-三唑键与选自双官能环氧化物和多官能环氧化物的第二交联剂相结合的官能化基团的官能化试剂，以获得含有官能化基团的交联HA。 该方法提供含有官能化基团的交联透明质酸（HA）。 该方法利用通过1,2,3-三唑键与交联剂偶联的官能化基团的官能化试剂。

    Oxidized derivative of hyaluronic acid, a method of preparation thereof and a method of modification thereof
    54.
    发明授权
    Oxidized derivative of hyaluronic acid, a method of preparation thereof and a method of modification thereof 有权
    透明质酸的氧化衍生物，其制备方法及其改性方法

    公开(公告)号：US09403918B2

    公开(公告)日：2016-08-02

    申请号：US13514759

    申请日：2010-12-10

    申请人： Radovan Buffa ,  Sofiane Kettou ,  Lucie Pospisilova ,  Miroslava Berkova ,  Vladimir Velebny

    发明人： Radovan Buffa ,  Sofiane Kettou ,  Lucie Pospisilova ,  Miroslava Berkova ,  Vladimir Velebny

    IPC分类号： C08B37/00 ,  C08B37/08

    CPC分类号： C08B37/0072

    摘要： The invention relates to a hyaluronic acid derivative and methods of preparation and modification of a hyaluronan derivative with an aldehydic group in the position (6) of the polysaccharide glucosamine part. The oxidation of the hyaluronic acid can be performed by means of Dess-Martin periodinane (DMP) agent. The prepared aldehyde can be used for binding amine, diamine, amino acid, peptide and other compounds containing an amino group, e.g. by means of the reductive amination with NaBH3CN in water or in a water-organic solvent system. When a diamine or compounds containing three or more amino groups are used, cross-linked hyaluronan derivatives can be prepared. Cross-linked derivatives can also be prepared by the reaction of the aldehyde with a hyaluronan substituted by an amino-alkyl group HA-alkyl-NH2.

    摘要翻译： 本发明涉及一种透明质酸衍生物以及多糖葡糖胺部位（6）中的醛基的透明质酸衍生物的制备和修饰方法。 透明质酸的氧化可以通过Dess-Martin高碘烷（DMP）剂进行。 所制备的醛可用于结合胺，二胺，氨基酸，肽和其它含有氨基的化合物，例如， 通过用NaBH 3 CN在水中或在水 - 有机溶剂体系中还原胺化。 当使用二胺或含有三个或多个氨基的化合物时，可以制备交联的透明质酸衍生物。 交联衍生物也可以通过醛与被氨基 - 烷基氨基烷基-NH 2取代的透明质酸的反应来制备。

    Process for producing water-soluble hyaluronic acid modification
    57.
    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：US09394379B2

    公开(公告)日：2016-07-19

    申请号：US13947716

    申请日：2013-07-22

    申请人： Chugai Seiyaku Kabushiki Kaisha

    发明人： Kenji Yasugi ,  Teruo Nakamura ,  Tsuyoshi Shimoboji ,  Mika Sato

    IPC分类号： C08B37/08 ,  C08J3/075 ,  A61K47/48 ,  C08J3/12 ,  C08L5/08

    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。

    Method for producing cross-linked hyaluronic acid
    58.
    发明授权
    Method for producing cross-linked hyaluronic acid 有权
    交联透明质酸的生产方法

    公开(公告)号：US09371402B2

    公开(公告)日：2016-06-21

    申请号：US13316840

    申请日：2011-12-12

    申请人： Tor-Chern Chen ,  Li-Su Chen

    发明人： Tor-Chern Chen ,  Li-Su Chen

    IPC分类号： C08B37/08

    CPC分类号： C08B37/0072

    摘要： A method for producing a cross-linked hyaluronic acid in accordance with the present invention comprises: (a) cross-linking at least one polymer at a temperature, from about 35° C. to about 60° C., for a reaction time of from about 0.1 hour to about 72 hours with a cross-linking agent; and (b) lowering the temperature in step (a) to form about 10° C. to about 30° C. for a reaction time of from about 48 hours to about 28 days to obtain the cross-linked hyaluronic acid, whereby, a cross-linking agent content in a product of the method can be decreased so the product does not require purification.

    摘要翻译： 根据本发明的生产交联透明质酸的方法包括：（a）在约35℃至约60℃的温度下将至少一种聚合物交联反应时间 用交联剂约0.1小时至约72小时; 和（b）在步骤（a）中降低温度以形成约10℃至约30℃，反应时间为约48小时至约28天，以获得交联的透明质酸，由此， 该方法的产品中的交联剂含量可以降低，因此产物不需要纯化。

    Process for preparing a crosslinked hyaluronic acid gel via homogenization in a deformable pouch
    59.
    发明授权
    Process for preparing a crosslinked hyaluronic acid gel via homogenization in a deformable pouch 有权
    在可变形袋中通过均化制备交联透明质酸凝胶的方法

    公开(公告)号：US09353194B2

    公开(公告)日：2016-05-31

    申请号：US13266638

    申请日：2010-05-07

    申请人： Francois Bourdon

    发明人： Francois Bourdon

    IPC分类号： C08B37/08 ,  A61K8/04 ,  A61K8/73 ,  A61Q19/08 ,  C08J3/075 ,  C08J3/24

    CPC分类号： C08B37/0072 ,  A61K8/042 ,  A61K8/735 ,  A61Q19/08 ,  C08J3/075 ,  C08J3/24 ,  C08J2305/08

    摘要： A process for preparing a crosslinked gel of at least one polymer or one of its salts, including a) providing an aqueous medium containing at least one polymer, b) forming a homogenous gel from the medium from step a), c) bringing the gel obtained in step b) into contact with an effective amount of at least one crosslinking agent; d) crosslinking the mixture formed in step c); and e) recovering the crosslinked hydrogel, wherein at least steps a) to d) are carried out within a hermetic cavity delimited at least partially by a deformable wall, the mixture present in the cavity being exposed, in step d), to conditions conducive to crosslinking.

    摘要翻译： 一种制备至少一种聚合物或其盐的交联凝胶的方法，包括a）提供含有至少一种聚合物的水性介质，b）从步骤a）的介质形成均匀的凝胶，c）使凝胶 在步骤b）中获得与有效量的至少一种交联剂接触; d）将步骤c）中形成的混合物交联; 和e）回收交联的水凝胶，其中至少步骤a）至d）在至少部分由可变形壁限定的密封腔内进行，在步骤d）中存在于空腔中的混合物暴露于有利条件 交联。