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1. 发明授权

US08137964B2 Method of producing three-dimensional tissue and method of producing extracellular matrix used in the same 有权
标题翻译：制备三维组织的方法及其制备方法
公开(公告)号：US08137964B2
公开(公告)日：2012-03-20
申请号：US11514468
申请日：2006-09-01
申请人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki , Yoshio Nakahara
发明人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki , Yoshio Nakahara
IPC分类号： C12N5/06
CPC分类号： C12N5/0068 , C12N5/0062 , C12N2533/52 , C12N2533/54 , Y10S977/902
摘要： The present invention provides a novel method of producing a three-dimensional tissue by which cell lamination can be carried out easily. According to the method, a three-dimensional tissue in which cell layers are laminated with an extracellular matrix intervening between each pair of the adjacent cell layers is produced by: (A) forming a cell layer on a substrate; (B) bringing the cell layer formed on the substrate into contact with a solution containing a first substance and a solution containing a second substance alternately, thus forming, on the cell layer, an extracellular matrix in which the first substance and the second substance are laminated alternately; and (C) culturing a cell on the extracellular matrix to form a further cell layer. In the present invention, a combination of the first substance and the second substance is (a) a combination of a protein or polymer having an RGD sequence and a protein or polymer that interacts with the protein or polymer having the RGD sequence or (b) a combination of a protein or polymer that is positively charged and a protein or polymer that is negatively charged.
摘要翻译：本发明提供一种可以容易地进行细胞层压的三维组织的制造方法。根据该方法，通过以下方法制造细胞层与介于每对相邻细胞层之间的细胞外基质层叠的三维组织：（A）在基材上形成细胞层; （B）使形成在基板上的细胞层与含有第一物质的溶液和含有第二物质的溶液交替接触，从而在细胞层上形成第一物质和第二物质为细胞外基质交替叠层; 和（C）在细胞外基质上培养细胞以形成另外的细胞层。在本发明中，第一物质和第二物质的组合是（a）具有RGD序列的蛋白质或聚合物和与具有RGD序列的蛋白质或聚合物相互作用的蛋白质或聚合物的组合，或（b）带正电荷的蛋白质或聚合物和带负电荷的蛋白质或聚合物的组合。

2. 发明申请

US20070207540A1 Method of producing three-dimensional tissue and method of producing extracellular matrix used in the same 有权
标题翻译：制备三维组织的方法及其制备方法
公开(公告)号：US20070207540A1
公开(公告)日：2007-09-06
申请号：US11514468
申请日：2006-09-01
申请人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki , Yoshio Nakahara
发明人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki , Yoshio Nakahara
IPC分类号： C12N5/06
CPC分类号： C12N5/0068 , C12N5/0062 , C12N2533/52 , C12N2533/54 , Y10S977/902
摘要： The present invention provides a novel method of producing a three-dimensional tissue by which cell lamination can be carried out easily. According to the method, a three-dimensional tissue in which cell layers are laminated with an extracellular matrix intervening between each pair of the adjacent cell layers is produced by: (A) forming a cell layer on a substrate; (B) bringing the cell layer formed on the substrate into contact with a solution containing a first substance and a solution containing a second substance alternately, thus forming, on the cell layer, an extracellular matrix in which the first substance and the second substance are laminated alternately; and (C) culturing a cell on the extracellular matrix to form a further cell layer. In the present invention, a combination of the first substance and the second substance is (a) a combination of a protein or polymer having an RGD sequence and a protein or polymer that interacts with the protein or polymer having the RGD sequence or (b) a combination of a protein or polymer that is positively charged and a protein or polymer that is negatively charged.
摘要翻译：本发明提供一种可以容易地进行细胞层压的三维组织的制造方法。根据该方法，通过以下方法制造细胞层与介于每对相邻细胞层之间的细胞外基质层叠的三维组织：（A）在基材上形成细胞层; （B）使形成在基板上的细胞层与含有第一物质的溶液和含有第二物质的溶液交替接触，从而在细胞层上形成第一物质和第二物质为细胞外基质交替叠层; 和（C）在细胞外基质上培养细胞以形成另外的细胞层。在本发明中，第一物质和第二物质的组合是（a）具有RGD序列的蛋白质或聚合物和与具有RGD序列的蛋白质或聚合物相互作用的蛋白质或聚合物的组合，或（b）带正电荷的蛋白质或聚合物和带负电荷的蛋白质或聚合物的组合。

3. 发明授权

US08263405B2 Controllably degradable hydrogel for culturing cells to produce three-dimensionally organized cells 有权
标题翻译：可控降解的水凝胶用于培养细胞以产生三维有组织的细胞
公开(公告)号：US08263405B2
公开(公告)日：2012-09-11
申请号：US12094973
申请日：2006-11-24
申请人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki
发明人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki
IPC分类号： C12N5/07 , C12N11/08
CPC分类号： C12N5/0068 , A61L27/52 , A61L27/58 , C08B37/003 , C08B37/0084 , C08J3/075 , C08J2305/04 , C08J2305/08 , C08J2377/04 , C12N5/0062 , C12N2533/30
摘要： To provide a new reductive-stimuli-responsive degradable gel that allows any control of decomposition of the three-dimensional base material for cell culture and production of a completely biological three-dimensional cellular structure consisting only of cells and cells-produced extracellular matrix and that allows safe recovery of the cellular structure produced. A stimuli-responsive hydrogel, characterized by being produced by crosslinking a water-soluble polymer with a compound having a disulfide bond in the molecular chain.
摘要翻译：提供新的还原刺激响应性可降解凝胶，其允许任何控制用于细胞培养的三维基质的分解和产生仅由细胞和细胞产生的细胞外基质组成的完全生物的三维细胞结构，并且允许安全地回收所生产的细胞结构。刺激响应性水凝胶，其特征在于通过在分子链中与具有二硫键的化合物交联水溶性聚合物来制备。

4. 发明申请

US20090117656A1 STIMULI-RESPONSIVE DEGRADABLE GEL 有权
标题翻译：刺激性可降解凝胶
公开(公告)号：US20090117656A1
公开(公告)日：2009-05-07
申请号：US12094973
申请日：2006-11-24
申请人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki
发明人： Mitsuru Akashi , Yoshiki Sawa , Michiya Matsusaki
IPC分类号： C12N5/02
CPC分类号： C12N5/0068 , A61L27/52 , A61L27/58 , C08B37/003 , C08B37/0084 , C08J3/075 , C08J2305/04 , C08J2305/08 , C08J2377/04 , C12N5/0062 , C12N2533/30
摘要： To provide a new reductive-stimuli-responsive degradable gel that allows any control of decomposition of the three-dimensional base material for cell culture and production of a completely biological three-dimensional cellular structure consisting only of cells and cells-produced extracellular matrix and that allows safe recovery of the cellular structure produced.A stimuli-responsive hydrogel, characterized by being produced by crosslinking a water-soluble polymer with a compound having a disulfide bond in the molecular chain.
摘要翻译：提供新的还原刺激响应性可降解凝胶，其允许任何控制用于细胞培养的三维基质的分解和产生仅由细胞和细胞产生的细胞外基质组成的完全生物的三维细胞结构，并且允许安全地回收所生产的细胞结构。刺激响应性水凝胶，其特征在于通过在分子链中与具有二硫键的化合物交联水溶性聚合物来制备。

5. 发明授权

US08835570B2 Hydrophilic material, medical material and sustained drug release material 有权
标题翻译：亲水材料，医疗材料和持续的药物释放材料
公开(公告)号：US08835570B2
公开(公告)日：2014-09-16
申请号：US13121604
申请日：2009-09-29
申请人： Mitsuru Akashi , Michiya Matsusaki , Dongjian Shi , Makoto Onishi , Yotaro Fujita
发明人： Mitsuru Akashi , Michiya Matsusaki , Dongjian Shi , Makoto Onishi , Yotaro Fujita
IPC分类号： C08G63/664 , C08G63/91 , A61K9/51
CPC分类号： C08G63/912 , A61K9/5153 , C08G63/664 , G01N2203/00
摘要： A hydrophilic material having a hydrophilic nature and being biocompatible and processable into nanoparticles wherein a hydrophilic monomer such as threitol or a hydrophilic polymer such as polyethylene glycol is attached to the βposition of an α,β-unsaturated carboxyl group of a (co)polymer comprising an aromatic compound such as 4-hydroxycinnamic acid in which an aromatic ring is substituted by the α,β-unsaturated carboxyl group and one or more hydroxyl groups. In particular, a hydrophilic material having a nanoparticle size which is highly dispersible in water, can well migrate into the blood and is useful as a drug carrier, a medical material and a sustained drug release material.
摘要翻译：亲水性材料具有亲水性并且可生物相容并可加工成纳米颗粒，其中亲水性单体例如苏糖醇或亲水性聚合物例如聚乙二醇被连接到（共聚物）的α，β-不饱和羧基的基团上）聚合物，其包含芳族化合物如4-羟基肉桂酸，其中芳环被α，β-不饱和羧基和一个或多个羟基取代。具体而言，具有高度分散于水中的纳米粒子尺寸的亲水性材料能很好地迁移到血液中，可用作药物载体，医疗材料和持续的药物释放材料。

6. 发明授权

US08389686B2 Noncovalent collagen crosslinking agent 失效
标题翻译：非共价胶原交联剂
公开(公告)号：US08389686B2
公开(公告)日：2013-03-05
申请号：US12990897
申请日：2009-05-01
申请人： Mitsuru Akashi , Kohji Nishida , Michiya Matsusaki , Akira Kubota , Tomonori Waku
发明人： Mitsuru Akashi , Kohji Nishida , Michiya Matsusaki , Akira Kubota , Tomonori Waku
IPC分类号： C07K14/78 , A61K38/00
CPC分类号： A61K38/39
摘要： The present invention provides a collagen crosslinking agent superior in biocompatibility that is free from the damage by UV irradiation and also from the problems of toxicity caused by residual monomer or unreacted functional groups. Provided is a noncovalent collagen crosslinking agent (for fibrous protein collagen), comprising a spacer of a polyvalent alcohol having two or more OH groups at the terminals and arms of collagen peptides formed of repetitions of three amino acids, the arms being bound via the OH groups to the spacer.
摘要翻译：本发明提供一种无生物相容性优异的胶原交联剂，其不受紫外线照射的损伤，也可由残留单体或未反应官能团引起的毒性问题。提供了一种非共价胶原交联剂（纤维蛋白胶原蛋白），其包含在末端具有两个或更多个OH基团的多元醇的隔离物和由三个氨基酸重复形成的胶原肽的臂，所述臂通过OH结合组到间隔物。

7. 发明授权

US07182884B2 Bio-liquid crystal polymer and shaped material using same 失效
标题翻译：生物液晶聚合物和使用其的成型材料
公开(公告)号：US07182884B2
公开(公告)日：2007-02-27
申请号：US10627995
申请日：2003-07-28
申请人： Tatsuo Kaneko , Michiya Matsusaki , Tran Thi Hang , Mitsuru Akashi , Naoto Kuriyama
发明人： Tatsuo Kaneko , Michiya Matsusaki , Tran Thi Hang , Mitsuru Akashi , Naoto Kuriyama
IPC分类号： C09K19/38 , C09K19/52 , A61K317/15 , C08G63/06 , C08G63/48
CPC分类号： C09K19/3866 , C09K19/3804
摘要： A bio-liquid crystal polymer is made from a tissue-derived compound or the derivatives. The bio-liquid crystal polymer has a characteristic of liquid crystal under predetermined conditions and is biocompatible.
摘要翻译：生物液晶聚合物由组织衍生的化合物或其衍生物制成。生物液晶聚合物在预定条件下具有液晶的特性并且是生物相容的。

8. 发明申请

US20060018870A1 Rigid polymer and method of making same 审中-公开
标题翻译：刚性聚合物及其制备方法
公开(公告)号：US20060018870A1
公开(公告)日：2006-01-26
申请号：US11191263
申请日：2005-07-28
申请人： Naoto Kuriyama , Mitsuru Akashi , Tatsuo Kaneko , Michiya Matsusaki , Tran Hang
发明人： Naoto Kuriyama , Mitsuru Akashi , Tatsuo Kaneko , Michiya Matsusaki , Tran Hang
IPC分类号： A61K31/74 , C08H1/06
CPC分类号： C08G63/06 , C08F220/04
摘要： A rigid polymer has: a homopolymer of one of a polymerizable bio-derived rigid compound having two or more reactive functional groups, a derivative of the bio-derived rigid compound, a hydrolyzed substance of the bio-derived rigid compound, a derivative of the hydrolyzed substance of the bio-derived rigid compound and the substances extracted from the bio resources, or copolymers of two or more of these compound, derivatives, and substances.
摘要翻译：刚性聚合物具有：具有两个或多个反应性官能团的可聚合生物衍生的刚性化合物之一的均聚物，生物衍生的刚性化合物的衍生物，生物衍生的刚性化合物的水解物质，生物衍生的刚性化合物的水解物质和从生物资源中提取的物质，或这些化合物，衍生物和物质中的两种或更多种的共聚物。

9. 发明申请

US20050018123A1 Bio-liquid crystal polymer and shaped material using same 失效
标题翻译：生物液晶聚合物和使用其的成型材料
公开(公告)号：US20050018123A1
公开(公告)日：2005-01-27
申请号：US10627995
申请日：2003-07-28
申请人： Tatsuo Kaneko , Michiya Matsusaki , Tran Hang , Mitsuru Akashi , Naoto Kuriyama
发明人： Tatsuo Kaneko , Michiya Matsusaki , Tran Hang , Mitsuru Akashi , Naoto Kuriyama
IPC分类号： C09K19/38 , C09K19/02
CPC分类号： C09K19/3866 , C09K19/3804
摘要： A bio-liquid crystal polymer is made from a tissue-derived compound or the derivatives. The bio-liquid crystal polymer has a characteristic of liquid crystal under predetermined conditions and is biocompatible.
摘要翻译：生物液晶聚合物由组织衍生的化合物或其衍生物制成。生物液晶聚合物在预定条件下具有液晶的特性并且是生物相容的。

10. 发明授权

US10073085B2 Method for producing artificial skin model, and artificial skin model 有权
公开(公告)号：US10073085B2
公开(公告)日：2018-09-11
申请号：US14008348
申请日：2012-03-29
申请人： Mitsuru Akashi , Michiya Matsusaki , Takeshi Sakura , Koji Hashimoto , Yuji Shirakata , Satoshi Hirakawa
发明人： Mitsuru Akashi , Michiya Matsusaki , Takeshi Sakura , Koji Hashimoto , Yuji Shirakata , Satoshi Hirakawa
IPC分类号： G01N33/50 , C12N5/071
CPC分类号： G01N33/5088 , C12N5/0698 , C12N2502/094 , C12N2502/1192 , C12N2502/1323 , C12N2502/28 , C12N2503/06 , C12N2533/52 , C12N2533/54
摘要： Provided is a novel method capable of producing an artificial skin model. A method for producing an artificial skin model includes: providing coated cells (1), each of which is obtained by covering the surface of a cell (3) with a coating film (2) containing an extracellular matrix component; forming a dermis tissue layer (7), in which the coated cells (1) are laminated, by culturing the coated cells (1); and forming an epidermis layer (12) by arranging epidermis cells (8) on the dermis tissue layer (7).

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