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1. 发明授权

US07465766B2 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US07465766B2
公开(公告)日：2008-12-16
申请号：US11176544
申请日：2005-07-07
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： C08L89/00 , C08G63/48
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, implantable tissue matrix material 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.
摘要翻译：提供了可用于人造组织和组织工程应用的二羟基苯基交联的大分子网络，特别是提供用于各种组织类型的合成的，可植入的组织基质材料。特别地，描述人造或合成软骨，声带材料，玻璃体材料，软组织材料和二尖瓣材料。在一个实施方案中，网络由酪胺取代和交联的透明质酸分子组成，其中通过可以在体内进行的过氧化物酶介导的二联胺连接来实现交联。二联苯键提供具有所需物理性质的稳定的，一致的透明质酸基水凝胶。

2. 发明申请

US20090143766A1 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US20090143766A1
公开(公告)日：2009-06-04
申请号：US12320613
申请日：2009-01-29
申请人： Anthony Calabro , Lee Akst , Daniel Alam , James Chan , Aniq B. Darr , Kiyotaka Fukumachi , 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 Fukumachi , Richard A. Gross , David Haynes , Keiji Kamohara , Daniel P. Knott , Hilel Lewis , Alex Melamud , Anthony Miniaci , Marshall Strome
IPC分类号： A61M37/00 , A61L27/52
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.
摘要翻译：提供了可用于人造组织和组织工程应用的二羟基苯基交联的大分子网络，特别是提供用于各种组织类型的合成大分子网络。特别地，描述人造或合成软骨，声带材料，玻璃体材料，软组织材料和二尖瓣材料。在一个实施方案中，网络由酪胺取代和交联的透明质酸分子组成，其中通过可以在体内进行的过氧化物酶介导的二联胺连接来实现交联。二联苯键提供具有所需物理性质的稳定的，一致的透明质酸基水凝胶。

3. 发明授权

US07368502B2 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US07368502B2
公开(公告)日：2008-05-06
申请号：US11198803
申请日：2005-08-05
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
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。

4. 发明授权

US08137688B2 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US08137688B2
公开(公告)日：2012-03-20
申请号：US12380469
申请日：2009-02-27
申请人： Peter A. Zahos , Anthony Calabro , Aniq B. Darr , Richard A. Gross
发明人： Peter A. Zahos , Anthony Calabro , Aniq B. Darr , Richard A. Gross
IPC分类号： C08G63/91 , C08G65/48 , A61K31/775
CPC分类号： A61K31/775 , A61L27/20 , A61L27/50 , A61L27/52 , A61L2400/06 , A61L2430/38 , C08B37/0069 , C08B37/0072 , C08L5/08 , C08L2205/02 , C12P19/04 , C08L2666/26
摘要： A synthetic nucleus pulposus is provided that is useful in treatment of degenerative disc disease, augmentation of a degenerate disc, and alleviation of back pain. In an embodiment the synthetic nucleus pulposus comprises hyaluronan macromolecules that have been cross-linked via dihydroxyphenyl linkages. The synthetic nucleus pulposus restores or improves the water-retention capability of the disc. A method of treating an intervertebral disc with the cross-linked hyaluronan macromolecules is also provided. A method of regenerative therapy to address loss of cells of nucleus pulposus of an intervertebral disc based on treatment with the cross-linked hyaluronan macromolecules and mesenchymal stem cells is also provided.
摘要翻译：提供了一种合成髓核，可用于治疗退行性椎间盘疾病，增加退行性椎间盘，减轻背部疼痛。在一个实施方案中，合成髓核包含已经通过二羟基苯基键交联的透明质酸大分子。合成髓核恢复或提高椎间盘的保水能力。还提供了用交联的透明质酸大分子治疗椎间盘的方法。还提供了一种基于用交联透明质酸大分子和间充质干细胞治疗来解决椎间盘髓核的细胞损失的再生治疗方法。

5. 发明授权

US08021350B2 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US08021350B2
公开(公告)日：2011-09-20
申请号：US12320613
申请日：2009-01-29
申请人： Anthony Calabro , Aniq B. Darr , Kiyotaka Fukamachi , Richard A. Gross , Keiji Kamohara , Michael K. Banbury
发明人： Anthony Calabro , Aniq B. Darr , Kiyotaka Fukamachi , Richard A. Gross , Keiji Kamohara , Michael K. Banbury
IPC分类号： C08G63/48 , C08G63/91 , A61K31/74
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.
摘要翻译：提供了可用于人造组织和组织工程应用的二羟基苯基交联的大分子网络，特别是提供用于各种组织类型的合成大分子网络。特别地，描述人造或合成软骨，声带材料，玻璃体材料，软组织材料和二尖瓣材料。在一个实施方案中，网络由酪胺取代和交联的透明质酸分子组成，其中通过可以在体内进行的过氧化物酶介导的二联胺连接来实现交联。二联苯键提供具有所需物理性质的稳定的，一致的透明质酸基水凝胶。

6. 发明申请

US20090252700A1 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US20090252700A1
公开(公告)日：2009-10-08
申请号：US12380469
申请日：2009-02-27
申请人： Peter A. Zahos , Anthony Calabro , Aniq B. Darr , Richard A. Gross
发明人： Peter A. Zahos , Anthony Calabro , Aniq B. Darr , Richard A. Gross
IPC分类号： A61K31/775 , C08G63/91 , C08G65/48 , C08B37/00 , A61P19/00
CPC分类号： A61K31/775 , A61L27/20 , A61L27/50 , A61L27/52 , A61L2400/06 , A61L2430/38 , C08B37/0069 , C08B37/0072 , C08L5/08 , C08L2205/02 , C12P19/04 , C08L2666/26
摘要： A synthetic nucleus pulposus is provided that is useful in treatment of degenerative disc disease, augmentation of a degenerate disc, and alleviation of back pain. In an embodiment the synthetic nucleus pulposus comprises hyaluronan macromolecules that have been cross-linked via dihydroxyphenyl linkages. The synthetic nucleus pulposus restores or improves the water-retention capability of the disc. A method of treating an intervertebral disc with the cross-linked hyaluronan macromolecules is also provided. A method of regenerative therapy to address loss of cells of nucleus pulposus of an intervertebral disc based on treatment with the cross-linked hyaluronan macromolecules and mesenchymal stem cells is also provided.
摘要翻译：提供了一种合成髓核，可用于治疗退行性椎间盘疾病，增加退行性椎间盘，减轻背部疼痛。在一个实施方案中，合成髓核包含已经通过二羟基苯基键交联的透明质酸大分子。合成髓核恢复或提高椎间盘的保水能力。还提供了用交联的透明质酸大分子治疗椎间盘的方法。还提供了一种基于用交联透明质酸大分子和间充质干细胞治疗来解决椎间盘髓核的细胞损失的再生治疗方法。

7. 发明授权

US08207262B2 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
标题翻译：羟基苯基交联大分子网络及其应用
公开(公告)号：US08207262B2
公开(公告)日：2012-06-26
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： C08G63/91 , C08G63/48
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.
摘要翻译：提供了可用于人造组织和组织工程应用的二羟基苯基交联的大分子网络，特别是提供用于各种组织类型的合成大分子网络。特别地，描述人造或合成软骨，声带材料，玻璃体材料，软组织材料和二尖瓣材料。在一个实施方案中，网络由酪胺取代和交联的透明质酸分子组成，其中通过可以在体内进行的过氧化物酶介导的二联胺连接来实现交联。二联苯键提供具有所需物理性质的稳定的，一致的透明质酸基水凝胶。

8. 发明授权

US08138265B2 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
公开(公告)号：US08138265B2
公开(公告)日：2012-03-20
申请号：US12320609
申请日：2009-01-29
申请人： Anthony Calabro , Aniq B. Darr , Richard A. Gross
发明人： Anthony Calabro , Aniq B. Darr , Richard A. Gross
IPC分类号： C08G63/91 , C08G63/48 , A61K31/74
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.

9. 发明申请

US20090142309A1 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
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.

10. 发明申请

US20090042294A1 Hydroxyphenyl cross-linked macromolecular network and applications thereof 有权
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.

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