公开(公告)号：US20090142309A1

公开(公告)日：2009-06-04

申请号：US12320609

申请日：2009-01-29

申请人： Anthony Calabro ,  Lee Akst ,  Daniel Alam ,  James Chan ,  Aniq B. Darr ,  Kiyotaka Fukamachi ,  Richard A. Gross ,  David Haynes ,  Keiji Kamohara ,  Daniel P. Knott ,  Hilel Lewis ,  Alex Melamud ,  Anthony Miniaci ,  Marshall Strome

发明人： Anthony Calabro ,  Lee Akst ,  Daniel Alam ,  James Chan ,  Aniq B. Darr ,  Kiyotaka Fukamachi ,  Richard A. Gross ,  David Haynes ,  Keiji Kamohara ,  Daniel P. Knott ,  Hilel Lewis ,  Alex Melamud ,  Anthony Miniaci ,  Marshall Strome

IPC分类号： A61K35/12 ,  C12P19/26 ,  A61K38/44

CPC分类号： C08J3/246 ,  C08B37/0072 ,  C08G73/02 ,  C08H1/00 ,  C08J3/24 ,  C12N5/0068 ,  C12N5/0655 ,  C12N2533/30

摘要： A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, particularly to provide a synthetic macromolecular network for a wide variety of tissue types. In particular, artificial or synthetic cartilage, vocal cord material, vitreous material, soft tissue material and mitral valve material are described. In an embodiment, the network is composed of tyramine-substituted and cross-linked hyaluronan molecules, wherein cross-linking is achieved via peroxidase-mediated dityramine-linkages that can be performed in vivo. The dityramine bonds provide a stable, coherent hyaluronan-based hydrogel with desired physical properties.

公开(公告)号：US20090042294A1

公开(公告)日：2009-02-12

申请号：US12283661

申请日：2008-09-15

申请人： Anthony Calabro ,  Lee Akst ,  Daniel Alam ,  James Chan ,  Aniq B. Darr ,  Kiyotaka Fukamachi ,  Richard A. Gross ,  David Haynes ,  Keiji Kamohara ,  Daniel P. Knott ,  Hilel Lewis ,  Alex Melamud ,  Anthony Miniaci ,  Marshall Strome

发明人： Anthony Calabro ,  Lee Akst ,  Daniel Alam ,  James Chan ,  Aniq B. Darr ,  Kiyotaka Fukamachi ,  Richard A. Gross ,  David Haynes ,  Keiji Kamohara ,  Daniel P. Knott ,  Hilel Lewis ,  Alex Melamud ,  Anthony Miniaci ,  Marshall Strome

IPC分类号： A61F2/02 ,  C08L5/00 ,  C08G63/12 ,  C08G65/38 ,  C08L89/00 ,  C12N5/08

CPC分类号： C08B37/0072 ,  A61K47/6903 ,  C08G73/02 ,  C08H1/00 ,  C08J3/24 ,  C08J3/246 ,  C12N5/0068 ,  C12N5/0655 ,  C12N2533/30

摘要： A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, particularly to provide a synthetic macromolecular network for a wide variety of tissue types. In particular, artificial or synthetic cartilage, vocal cord material, vitreous material, soft tissue material and mitral valve material are described. In an embodiment, the network is composed of tyramine-substituted and cross-linked hyaluronan molecules, wherein cross-linking is achieved via peroxidase-mediated dityramine-linkages that can be performed in vivo. The dityramine bonds provide a stable, coherent hyaluronan-based hydrogel with desired physical properties.

公开(公告)号：US06982298B2

公开(公告)日：2006-01-03

申请号：US10753779

申请日：2004-01-08

申请人： Anthony Calabro ,  Richard A. Gross ,  Aniq B. Darr

发明人： Anthony Calabro ,  Richard A. Gross ,  Aniq B. Darr

IPC分类号： C08L89/00 ,  C08G63/48 ,  C08G63/91

CPC分类号： A61L27/52 ,  A61K47/34 ,  A61K47/36 ,  A61K47/42 ,  A61L27/14 ,  C08G63/81 ,  C08G73/02 ,  C08J3/075 ,  C08L101/14

摘要： A dihydroxyphenyl cross-linked macromolecular network is provided that is useful in artificial tissue and tissue engineering applications, such as artificial or synthetic cartilage. The network is made by first providing a polyamine or polycarboxylate macromolecule (having a plurality of amine or carboxylic acid groups respectively attached along the length of the molecule), reacting this macromolecule with a hydroxyphenyl compound having a free carboxylic acid group in the case of a polyamine or a free primary amine group in the case of a polycarboxylate, and substituting the hydroxyphenyl compound onto the macromolecule via a carbodiimide-mediated reaction pathway to provide a hydroxyphenyl-substituted macromolecule. This macromolecule is then linked to other such macromolecules via an enzyme catalyzed dimerization reaction between two hydroxyphenyl groups attached respectively to different macromolecules under metabolic conditions of temperature and pH. In a preferred embodiment, the macromolecular network is made up of tyramine-substituted hyaluronan molecules that are linked by dityramine bonds to provide a stable, coherent hydrogel with desired physical properties. A method of preparing such a network is also provided.

摘要翻译： 提供二羟基苯基交联的大分子网络，其可用于人造或组织工程应用，例如人造或合成软骨。 通过首先提供多胺或多羧酸盐大分子（沿着分子长度分别具有多个胺或羧酸基团）制备网络，使该高分子与具有游离羧酸基团的羟基苯基化合物反应 多胺或游离的伯胺基，并且通过碳二亚胺介导的反应途径将羟基苯基化合物取代到大分子上以提供羟基苯基取代的大分子。 然后通过在温度和pH值的代谢条件下分别连接到不同的大分子上的两个羟基苯基之间的酶催化的二聚反应将该大分子连接到其它这样的大分子。 在优选的实施方案中，大分子网络由酪胺取代的透明质酸分子组成，其通过二苯胺键连接以提供具有所需物理性质的稳定的，连贯的水凝胶。 还提供了一种制备这种网络的方法。