公开(公告)号：US09212259B2

公开(公告)日：2015-12-15

申请号：US13877384

申请日：2011-10-04

申请人： Won Jong Kim ,  Yanggy Lee ,  Kwideok Park ,  Jihoon Kim ,  Dong Keun Han

发明人： Won Jong Kim ,  Yanggy Lee ,  Kwideok Park ,  Jihoon Kim ,  Dong Keun Han

IPC分类号： A61K47/34 ,  A61L27/34 ,  C08L71/02 ,  C08G73/02 ,  A61L27/54 ,  C08G63/685

CPC分类号： C08G73/024 ,  A61K47/34 ,  A61L27/34 ,  A61L27/54 ,  A61L2300/114 ,  C08G63/6852 ,  C08G73/0206 ,  C08L71/02

摘要： A donor capable of controlled release of nitric monoxide and a prosthetic implant whose surface is coated with this donor are disclosed. The donor comprises a main chain of an organic polymer and a side chain that is covalently linked to the main chain and has a diazeniumdiolate functional group. The donor for controlled release of nitric monoxide exists in a fluid state such as liquid at room temperature and undergoes a sol-to-gel phase transition at a physiological pH as the temperature increases above the critical temperature. The critical temperature of the phase transition is in the range of 25 to 35° C., and the gel is a hydrogel without chemical cross-links.

摘要翻译： 公开了能够控制释放一氧化氮的供体和其表面涂覆有该供体的假体植入物。 供体包括有机聚合物的主链和共价连接到主链并具有二氮烯二硫酸酯官能团的侧链。 用于控制释放一氧化氮的供体以室温下的液体状态存在，并且随着温度升高到临界温度以上，在生理pH下经历溶胶 - 凝胶相变。 相变的临界温度在25至35℃的范围内，凝胶是没有化学交联的水凝胶。

公开(公告)号：US20090317478A1

公开(公告)日：2009-12-24

申请号：US12255163

申请日：2008-10-21

申请人： Dong Keun HAN ,  Kwideok Park ,  Jae-Jin Kim ,  Jun Sik Son ,  Soon Eon Bae

发明人： Dong Keun HAN ,  Kwideok Park ,  Jae-Jin Kim ,  Jun Sik Son ,  Soon Eon Bae

IPC分类号： A61K9/14 ,  A61K38/21

CPC分类号： A61K9/1647 ,  A61K9/1694 ,  A61K38/00

摘要： The present invention relates to covered porous biodegradable polymer microspheres for sustained-release drug delivery and tissue regeneration which has an interconnected inner open pore structure having a wide surface area and high porosity and an outer closed pore structure in which the surface of the microsphere is covered with a thin layer of a biodegradable polymer, and thereby the pores formed on the surface and exposed to the outside are closed; and methods for preparing the same. Due to such a characteristic pore structure, the covered porous biodegradable polymer microspheres according to the present invention can prevent the biologically active material from being excessively released in the early stage immediately after administration, and after that, can gradually release the biologically active material through the interconnected inner pore structure over a prolonged period as the biodegradable polymer thin layer is degraded. Therefore, the microsphere of the present invention can be effectively used for sustained-release drug delivery and tissue regeneration.

摘要翻译： 本发明涉及用于持续释放药物递送和组织再生的覆盖多孔可生物降解聚合物微球，其具有互连的具有宽表面积和高孔隙率的内开孔结构以及微球表面被覆盖的外封闭孔结构 具有可生物降解聚合物的薄层，从而形成在表面上并暴露于外部的孔闭合; 及其制备方法。 由于这样的特征性的孔结构，本发明的被覆多孔生物降解性聚合物微球体可以防止生物活性物质在给药后立即早期过度释放，之后可以通过使用生物活性物质逐渐释放生物活性物质 随着可生物降解的聚合物薄层的退化，延长的互连内孔结构。 因此，本发明的微球体可以有效地用于缓释药物递送和组织再生。

公开(公告)号：US08192655B2

公开(公告)日：2012-06-05

申请号：US12255163

申请日：2008-10-21

申请人： Dong Keun Han ,  Kwideok Park ,  Jae-Jin Kim ,  Jun Sik Son ,  Soon Eon Bae

发明人： Dong Keun Han ,  Kwideok Park ,  Jae-Jin Kim ,  Jun Sik Son ,  Soon Eon Bae

IPC分类号： B29B9/00

CPC分类号： A61K9/1647 ,  A61K9/1694 ,  A61K38/00

摘要： The present invention relates to covered porous biodegradable polymer microspheres for sustained-release drug delivery and tissue regeneration which has an interconnected inner open pore structure having a wide surface area and high porosity and an outer closed pore structure in which the surface of the microsphere is covered with a thin layer of a biodegradable polymer, and thereby the pores formed on the surface and exposed to the outside are closed; and methods for preparing the same. Due to such a characteristic pore structure, the covered porous biodegradable polymer microspheres according to the present invention can prevent the biologically active material from being excessively released in the early stage immediately after administration, and after that, can gradually release the biologically active material through the interconnected inner pore structure over a prolonged period as the biodegradable polymer thin layer is degraded. Therefore, the microsphere of the present invention can be effectively used for sustained-release drug delivery and tissue regeneration.

摘要翻译： 本发明涉及用于持续释放药物递送和组织再生的覆盖多孔可生物降解聚合物微球，其具有互连的具有宽表面积和高孔隙率的内开孔结构以及微球表面被覆盖的外封闭孔结构 具有可生物降解聚合物的薄层，从而形成在表面上并暴露于外部的孔闭合; 及其制备方法。 由于这样的特征性的孔结构，本发明的被覆多孔生物降解性聚合物微球体可以防止生物活性物质在给药后立即早期过度释放，之后可以通过使用生物活性物质逐渐释放生物活性物质 随着可生物降解的聚合物薄层的退化，延长的互连内孔结构。 因此，本发明的微球体可以有效地用于缓释药物递送和组织再生。

公开(公告)号：US20100098762A1

公开(公告)日：2010-04-22

申请号：US12573037

申请日：2009-10-02

申请人： Dong Keun Han ,  Kwideok Park ,  Jae-Jin Kim

发明人： Dong Keun Han ,  Kwideok Park ,  Jae-Jin Kim

IPC分类号： A61K9/10 ,  A61K38/18 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  A61P19/04

CPC分类号： A61K9/06 ,  A61K47/10 ,  A61K47/60

摘要： The present invention relates to a thermosensitive pluronic derivative hydrogel for tissue regeneration in which a biodegradable polymer is introduced at one end or both ends of a pluronic polymer, a methacryloxyethyl trimellitic acid anhydride is conjugated to the biodegradable polymer, and a physiologically active substance is fixed to the methacryloxyethyl trimellitic acid anhydride, as well as a method for the preparation thereof. The pluronic derivative hydrogel according to the present invention exhibits high biodegradability due to the introduction of a biodegradable polymer while still maintaining the themosensitivity of the pluronic polymer itself and shows good biocompatibility owing to the coupling with a physiologically active substance capable of improving cell adhesion, proliferation and differentiation. Therefore, the pluronic derivative hydrogel according to the present invention can be effectively used in the regeneration of various kinds of tissues and organs.

摘要翻译： 本发明涉及用于组织再生的热敏普朗尼克衍生物水凝胶，其中在聚醚聚合物的一端或两端引入可生物降解的聚合物，将甲基丙烯酰氧基乙基偏苯三酸酐与可生物降解的聚合物缀合，并且将生理活性物质固定 到甲基丙烯酰氧基乙基偏苯三酸酐，以及其制备方法。 本发明的聚醚衍生物水凝胶由于引入生物可降解聚合物而具有高生物降解性，同时仍然保持了普鲁隆聚合物本身的敏感性，并且由于与能够改善细胞粘附，增殖的生理活性物质的偶联而显示出良好的生物相容性 和分化。 因此，根据本发明的普流纶衍生物水凝胶可以有效地用于各种组织和器官的再生。

公开(公告)号：US20110263018A1

公开(公告)日：2011-10-27

申请号：US12902537

申请日：2010-10-12

申请人： Kwideok PARK ,  Dong Keun Han ,  Dong Hoon Choi ,  Jae-Jin Kim ,  Hee Joong Kim ,  Heung Jae Chun

发明人： Kwideok PARK ,  Dong Keun Han ,  Dong Hoon Choi ,  Jae-Jin Kim ,  Hee Joong Kim ,  Heung Jae Chun

IPC分类号： C12N5/02 ,  C12N5/00

CPC分类号： C12N5/0075 ,  A61K9/1647 ,  A61K9/5036 ,  C12N2533/40

摘要： The present invention relates to a method of preparing a delivery system capable of loading bioactive growth factors that are essential for the differentiation and proliferation of cells and is characterized as loading at least two types of components comprising growth factors in a single carrier, whereby the release of each of the plurality of growth factors can be temporally controlled. Specifically, the method of preparing a microcapsule type growth factor delivery system according to the present invention includes: (1) preparing a polymeric microsphere comprising a first component, and then encapsulating the microspheres by electrodropping the polymer microsphere into another polymer comprising a second component, thereby manufacturing a core-shell structured, microcapsule type delivery system, or (2) encapsulating a polymer solution comprising a first component by electrodropping the polymer solution into another polymer comprising a second component, thereby manufacturing a core-shell structured microcapsule type delivery system. The present invention also provides a stem cell differentiation method involving bringing a microcapsule type delivery system loaded with multiple growth factors according to the present invention into contact with stem cells.

摘要翻译： 本发明涉及一种制备能够载入对细胞分化和增殖至关重要的生物活性生长因子的递送系统的方法，其特征在于将至少两种包含生长因子的组分装载在单个载体中，由此释放 可以暂时控制多个生长因子中的每一个。 具体而言，本发明的微胶囊型生长因子递送系统的制备方法包括：（1）制备包含第一成分的聚合物微球体，然后通过将聚合物微球体电渗入另一种包含第二组分的聚合物中来包封微球体， 从而制造芯壳结构的微胶囊型输送系统，或（2）通过将聚合物溶液电渗到另一种包含第二组分的聚合物中，将包含第一组分的聚合物溶液包封，由此制造核 - 壳结构的微胶囊型递送系统。 本发明还提供一种干细胞分化方法，其包括使根据本发明的负载有多种生长因子的微胶囊型递送系统与干细胞接触。

公开(公告)号：US20100129422A1

公开(公告)日：2010-05-27

申请号：US12473850

申请日：2009-05-28

申请人： Dong Keun HAN ,  Kwideok Park ,  Jae-Jin Kim ,  Soon Eon Bae

发明人： Dong Keun HAN ,  Kwideok Park ,  Jae-Jin Kim ,  Soon Eon Bae

IPC分类号： A61F2/00

CPC分类号： A61L27/50 ,  A61L27/18 ,  A61L27/54 ,  A61L27/56 ,  A61L2300/25 ,  A61L2300/414 ,  A61L2300/428 ,  A61L2300/43 ,  A61L2300/45 ,  A61L2300/604 ,  A61L2400/18 ,  C08L67/04

摘要： The present invention relates to an intelligent porous biodegradable polymer scaffold for in situ tissue regeneration in which two kinds of physiologically active substances having high differentiation potential and biocompatibility are introduced into the polymer scaffold and conjugated to the surface thereof, respectively, and a method for the preparation thereof. Since the intelligent porous biodegradable polymer scaffold exhibits improved biocompatibility and differentiation potential due to the introduction of physiologically active substances capable of efficiently inducing cell proliferation and differentiation into both the surface and the inside thereof, it can directly induce in situ tissue regeneration of the musculoskeletal system from stem cells in a living tissue after transplanting the polymer scaffold and stem cells into a human body without additional in vitro cultivation. Therefore, the intelligent porous biodegradable polymer scaffold according to the present invention can be effectively used in the regeneration of various kinds of tissues and organs including the musculoskeletal system.

摘要翻译： 本发明涉及一种用于原位组织再生的智能多孔可生物降解聚合物支架，其中将具有高分化潜能和生物相容性的两种生理活性物质分别引入聚合物支架并与其表面共轭， 的制备。 由于智能多孔生物可降解聚合物支架由于引入能够有效诱导细胞增殖和分化至其表面和内部的生理活性物质而显示出改善的生物相容性和分化潜能，因此可直接诱导肌肉骨骼系统的原位组织再生 从移植聚合物支架和干细胞到人体中的生物体组织中的干细胞，而不需要额外的体外培养。 因此，根据本发明的智能多孔生物可降解聚合物支架可以有效地用于包括肌肉骨骼系统在内的各种组织和器官的再生。

公开(公告)号：US20130189340A1

公开(公告)日：2013-07-25

申请号：US13877384

申请日：2011-10-04

申请人： Won Jong Kim ,  Yanggy Lee ,  Kwideok Park ,  Jihoon Kim ,  Dong Keun Han

发明人： Won Jong Kim ,  Yanggy Lee ,  Kwideok Park ,  Jihoon Kim ,  Dong Keun Han

IPC分类号： C08G73/02 ,  A61L27/34

CPC分类号： C08G73/024 ,  A61K47/34 ,  A61L27/34 ,  A61L27/54 ,  A61L2300/114 ,  C08G63/6852 ,  C08G73/0206 ,  C08L71/02

摘要： A donor capable of controlled release of nitric monoxide and a prosthetic implant whose surface is coated with this donor are disclosed. The donor comprises a main chain of an organic polymer and a side chain that is covalently linked to the main chain and has a diazeniumdiolate functional group. The donor for controlled release of nitric monoxide exists in a fluid state such as liquid at room temperature and undergoes a sol-to-gel phase transition at a physiological pH as the temperature increases above the critical temperature. The critical temperature of the phase transition is in the range of 25 to 35° C., and the gel is a hydrogel without chemical cross-links.

摘要翻译： 公开了能够控制释放一氧化氮的供体和其表面涂覆有该供体的假体植入物。 供体包括有机聚合物的主链和共价连接到主链并具有二氮烯二硫酸酯官能团的侧链。 用于控制释放一氧化氮的供体以室温下的液体状态存在，并且随着温度升高到临界温度以上，在生理pH下经历溶胶 - 凝胶相变。 相变的临界温度在25至35℃的范围内，凝胶是没有化学交联的水凝胶。

公开(公告)号：US20130101635A1

公开(公告)日：2013-04-25

申请号：US13650670

申请日：2012-10-12

申请人： Kwideok PARK ,  Soon Eon BAE ,  Dong Keun HAN

发明人： Kwideok PARK ,  Soon Eon BAE ,  Dong Keun HAN

IPC分类号： C12N5/00 ,  A61K35/32 ,  A61K35/28

CPC分类号： C12N5/0062 ,  A61K35/28 ,  A61K35/32 ,  C12N2533/90

摘要： Methods of preparing a self-assembled matrix from cell-derived extracellular matrice, and of inducing cell proliferation and differentiation by using the self-assembled matrix, and applying the self-assembled matrix into cell therapy. In detail, unique extracellular matrices obtained from particular cells are collected and then subjected to decellularization in order to form a self-assembled matrix including nano fibers only formed of extracellular matrix. In addition, the matrix prepared as described above provides a platform that is effective for the induction of the mass proliferation or differentiation of cells, and thus, may be applied in manufacturing cell therapy products.

摘要翻译： 从细胞衍生的细胞外基质制备自组装基质的方法，以及通过使用自组装基质诱导细胞增殖和分化，以及将自组装基质应用于细胞治疗。 详细地，从特定细胞获得的独特的细胞外基质被收集，然后进行脱细胞化以形成仅由细胞外基质形成的纳米纤维的自组装基质。 此外，如上所述制备的基质提供了对诱导细胞的大量增殖或分化有效的平台，因此可以应用于制造细胞治疗产品。

公开(公告)号：US20100136645A1

公开(公告)日：2010-06-03

申请号：US12596008

申请日：2007-04-17

申请人： Byoung-Hyun Min ,  So Ra Park ,  Cheng Zhe Jin ,  Kwideok Park

发明人： Byoung-Hyun Min ,  So Ra Park ,  Cheng Zhe Jin ,  Kwideok Park

IPC分类号： C12N13/00 ,  C12N5/02

CPC分类号： C12N5/0655 ,  A61L27/3633 ,  A61L27/3817 ,  A61L27/48 ,  A61L27/56 ,  C12N2533/54 ,  C12N2533/90 ,  C08L67/04

摘要： The present invention relates to a method for fabricating a cell-derived extracellular matrix scaffold, more particularly, to a method for fabricating a cell-derived extracellular matrix scaffold, the method comprising the steps of obtaining a chondrocyte/extracellular matrix (ECM) membrane from chondrocytes derived from animal cartilage, obtaining a pellet-type scaffold-free construct by culturing after centrifuging the obtained chondrocytes/extracellular matrix (ECM) membrane and freeze-drying the obtained pellet-type construct. The cell-derived ECM scaffold according to the invention is a porous scaffold fabricated using cartilage tissue engineered by culturing chondrocytes in an in vitro scaffold-free system, which is not reduced in size during the cultivation and thus useful for cartilage regeneration.

摘要翻译： 本发明涉及一种用于制备细胞衍生的细胞外基质支架的方法，更具体地涉及一种制备细胞衍生的细胞外基质支架的方法，所述方法包括以下步骤：从软骨细胞/细胞外基质（ECM） 从动物软骨衍生的软骨细胞，通过在离心获得的软骨细胞/细胞外基质（ECM）膜并冷冻干燥获得的颗粒型构建体之后培养获得颗粒型无支架构建体。 根据本发明的细胞衍生的ECM支架是使用在体外无支架体系中培养软骨细胞工程化的软骨组织制造的多孔支架，其在培养期间尺寸不减小，因此可用于软骨再生。

公开(公告)号：US08956643B2

公开(公告)日：2015-02-17

申请号：US12473850

申请日：2009-05-28

申请人： Dong Keun Han ,  Kwideok Park ,  Jae-Jin Kim ,  Soon Eon Bae

发明人： Dong Keun Han ,  Kwideok Park ,  Jae-Jin Kim ,  Soon Eon Bae

IPC分类号： A61F2/00 ,  A61F13/00 ,  A61L27/50 ,  A61L27/18 ,  A61L27/54 ,  A61L27/56

CPC分类号： A61L27/50 ,  A61L27/18 ,  A61L27/54 ,  A61L27/56 ,  A61L2300/25 ,  A61L2300/414 ,  A61L2300/428 ,  A61L2300/43 ,  A61L2300/45 ,  A61L2300/604 ,  A61L2400/18 ,  C08L67/04

摘要： The present invention relates to an intelligent porous biodegradable polymer scaffold for in situ tissue regeneration in which two kinds of physiologically active substances having high differentiation potential and biocompatibility are introduced into the polymer scaffold and conjugated to the surface thereof, respectively, and a method for the preparation thereof. Since the intelligent porous biodegradable polymer scaffold exhibits improved biocompatibility and differentiation potential due to the introduction of physiologically active substances capable of efficiently inducing cell proliferation and differentiation into both the surface and the inside thereof, it can directly induce in situ tissue regeneration of the musculoskeletal system from stem cells in a living tissue after transplanting the polymer scaffold and stem cells into a human body without additional in vitro cultivation. Therefore, the intelligent porous biodegradable polymer scaffold according to the present invention can be effectively used in the regeneration of various kinds of tissues and organs including the musculoskeletal system.

摘要翻译： 本发明涉及一种用于原位组织再生的智能多孔可生物降解聚合物支架，其中将具有高分化潜能和生物相容性的两种生理活性物质分别引入聚合物支架并与其表面共轭， 的制备。 由于智能多孔生物可降解聚合物支架由于引入能够有效诱导细胞增殖和分化至其表面和内部的生理活性物质而显示出改善的生物相容性和分化潜能，因此可直接诱导肌肉骨骼系统的原位组织再生 从移植聚合物支架和干细胞到人体中的生物体组织中的干细胞，而不需要额外的体外培养。 因此，根据本发明的智能多孔生物可降解聚合物支架可以有效地用于包括肌肉骨骼系统在内的各种组织和器官的再生。