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1. 发明申请

WO2009023276A1 SEQUENTIAL COUPLING OF BIOMOLECULE LAYERS TO POLYMERS 审中-公开
标题翻译：生物分子层向聚合物的顺序耦合
公开(公告)号：WO2009023276A1
公开(公告)日：2009-02-19
申请号：PCT/US2008/009806
申请日：2008-08-15
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , MYUNG, David , BECK, Stayce , NOOLANDI, Jaan , TA, Christopher, N. , COCHRAN, Jennifer, R. , FRANK, Curtis, W.
发明人： MYUNG, David , BECK, Stayce , NOOLANDI, Jaan , TA, Christopher, N. , COCHRAN, Jennifer, R. , FRANK, Curtis, W.
IPC分类号： A61L27/14 , A61L27/52 , A61L27/54 , A61F2/14
CPC分类号： A61L27/34 , A61L15/32 , A61L27/14 , A61L27/48 , C08L89/00
摘要： A bio-mimetic or bio-implantable material based on a sequential process of coupling biomolecule layers to a polymer layer is provided. In general, the material could be based on two or more biomolecule layers starting with one of the layers covalently linked to the polymer layer via cross-linkers and the other layers sequentially and covalently linked using cross-linkers to the previously added layer. The polymer layer could be a hydrogel or an interpenetrating polymer network hydrogel. The first layer of biomolecules could be a collagen type, fibronectin, laminin, extracellular matrix protein, or any combinations thereof. The second layer of biomolecules typically is a growth factor, protein or stimulant. The cross-linkers are either water soluble or insoluble bifunctional cross-linkers or azide-active-ester crosslinkers. The material and process as taught in this invention are useful in the field of tissue engineering and wound healing.
摘要翻译：提供了基于将生物分子层耦合到聚合物层的顺序方法的生物模拟或生物可植入材料。通常，该材料可以基于两个或更多个生物分子层，其起始于通过交联剂共价连接到聚合物层的层之一，并且其它层使用交联剂顺序并共价连接到先前添加的层。聚合物层可以是水凝胶或互穿聚合物网络水凝胶。第一层生物分子可以是胶原型，纤连蛋白，层粘连蛋白，细胞外基质蛋白或其任何组合。第二层生物分子通常是生长因子，蛋白质或兴奋剂。交联剂是水溶性或不溶性双功能交联剂或叠氮化物 - 活性酯交联剂。本发明教导的材料和方法可用于组织工程和伤口愈合领域。

2. 发明申请

WO2008130604A2 HYDROGEL ARTHROPLASTY DEVICE 审中-公开
公开(公告)号：WO2008130604A2
公开(公告)日：2008-10-30
申请号：PCT/US2008004976
申请日：2008-04-17
申请人： UNIV LELAND STANFORD JUNIOR , MYUNG DAVID , KOURTIS LAMPROS , HARTMANN LAURA , FRANK CURTIS W , GOODMAN STUART B , CARTER DENNIS R
发明人： MYUNG DAVID , KOURTIS LAMPROS , HARTMANN LAURA , FRANK CURTIS W , GOODMAN STUART B , CARTER DENNIS R
IPC分类号： A61F2/30 , A61L27/52
CPC分类号： A61L27/52 , A61F2/30756 , A61F2/32 , A61F2/34 , A61F2/3603 , A61F2/38 , A61F2/3859 , A61F2/389 , A61F2002/30075 , A61F2002/30077 , A61F2002/30324 , A61F2002/30616 , A61F2002/30673 , A61F2002/3092 , A61F2002/30937 , A61F2002/30971 , A61F2002/3225 , A61F2002/3491 , A61F2002/4631 , A61F2210/0061 , A61F2210/0066 , A61F2250/0036 , A61F2310/00796 , A61L27/425 , A61L27/56
摘要： An arthroplasty device is provided having an interpenetrating polymer network (IPN) hydrogel that is strain-hardened by swelling and adapted to be held in place in a joint by conforming to a bone geometry. The strain-hardened IPN hydrogel is based on two different networks: (1) a non-silicone network of preformed hydrophilic non-ionic telechelic macromonomers chemically cross-linked by polymerization of its end-groups, and (2) a non-silicone network of ionizable monomers. The second network was polymerized and chemically cross-linked in the presence of the first network and has formed physical cross-links with the first network. Within the IPN, the degree of chemical cross-linking in the second network is less than in the first network. An aqueous salt solution (neutral pH) is used to ionize and swell the second network. The swelling of the second network is constrained by the first network resulting in an increase in effective physical cross-links within the IPN.
摘要翻译：提供了一种具有互穿聚合物网络（IPN）水凝胶的关节成形术装置，其通过溶胀变形硬化并且适于通过符合骨几何形状在关节中保持就位。应变硬化IPN水凝胶基于两个不同的网络：（1）通过其端基聚合化学交联的预先形成的亲水非离子遥爪大分子单体的非硅氧烷网络，和（2）非硅氧烷网络的可离子化单体。第二个网络在第一个网络的存在下被聚合和化学交联，并与第一个网络形成了物理交叉连接。在IPN中，第二网络中的化学交联程度小于第一网络中的化学交联度。使用盐水溶液（中性pH）来电离和膨胀第二网络。第二个网络的肿胀受到第一个网络的限制，导致IPN内有效的物理交叉链路的增加。

3. 发明申请

WO2008097616A1 HYDROGEL-METAL ASSEMBLY 审中-公开
标题翻译：氢化金属组件
公开(公告)号：WO2008097616A1
公开(公告)日：2008-08-14
申请号：PCT/US2008/001642
申请日：2008-02-06
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , MYUNG, David , MUIR, Beinn, V.O. , FRANK, Curtis, W.
发明人： MYUNG, David , MUIR, Beinn, V.O. , FRANK, Curtis, W.
IPC分类号： B32B15/04
CPC分类号： A61L27/34 , A61L27/06 , A61L2400/18 , B32B15/04 , Y10T428/24355 , Y10T428/269 , Y10T428/31536 , Y10T428/31678
摘要： A hydrogel-metal assembly is provided. An intervening polymer network is used to bond together a water-swollen hydrogel layer and a biocompatible surface-modified metallic layer. The hydrogel layer is a water-swollen hydrogel layer of at least two interpenetrating polymers. The surface of the biocompatible surface-modified metallic layer is surface-modified with an inorganic material. The intervening polymer network has been chemically grafted to the inorganic material of the biocompatible surface-modified metallic layer through bi-functional linker molecules. The intervening polymer network is further physically or chemically cross-linked with the polymers of the water-swollen hydrogel. The hydrogel-metal assembly can be adapted to form a medical device, medical implant, an artificial implant, an orthopedic implant, or at least as part of a joint. The hydrogel-metal assembly is attractive for use as such implants or devices due to its characteristics such as, for example, low coefficient of friction, impact-absorption capacity or strength, and/or biocompatibility.
摘要翻译：提供了一种水凝胶 - 金属组件。中间聚合物网络用于将水溶胀的水凝胶层和生物相容的表面改性金属层结合在一起。水凝胶层是至少两个互穿聚合物的水溶胀水凝胶层。生物相容性表面改性金属层的表面用无机材料进行表面改性。中间聚合物网络已经通过双功能连接分子化学接枝到生物相容性表面改性金属层的无机材料上。中间聚合物网络进一步与水溶胀的水凝胶的聚合物物理或化学交联。水凝胶 - 金属组件可以适于形成医疗装置，医疗植入物，人造植入物，矫形植入物，或者至少作为关节的一部分。水凝胶 - 金属组件由于其特征例如低摩擦系数，冲击吸收能力或强度和/或生物相容性而具有吸引力用于这种植入物或装置。

4. 发明申请

WO2006116137A3 ARTIFICIAL CORNEA 审中-公开
公开(公告)号：WO2006116137A3
公开(公告)日：2006-11-02
申请号：PCT/US2006/015173
申请日：2006-04-21
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , MYUNG, David , TA, Christopher , FAROOQUI, Nabeel , CURTIS, Frank, W. , KOH, Won-gun , KO, Jungmin , NOOLANDI, Jaan , CARRASCO, Michael, R.
发明人： MYUNG, David , TA, Christopher , FAROOQUI, Nabeel , CURTIS, Frank, W. , KOH, Won-gun , KO, Jungmin , NOOLANDI, Jaan , CARRASCO, Michael, R.
IPC分类号： A61F2/16
摘要： The present invention provides an artificial corneal implant (100) having an optically clear central core (110) and a porous, hydrophihc, biocompatible skirt ( 120) perpheral to the central core (110) In one embodiment, the central core (110) is made of an interpenetrating double network hydrogel and the skirt (120) is made of poly(2-hydroxyethyl acrylate In another embodiment, both the central core (110) and the skirt (120) are made of interpenetrating double network hydrogels The implant (100) may also have interdiffusion zone (130) in which the skirt (120) component is interpenetrated with the core (110) component, or vice versa In a preferred embodiment, biomolecules are linked to the skirt (120), core (110), or both These biomolecules are preferably molecules that support epithelial and/or fibroblast cell survival and growth The present invention also provides a method of making an artificial corneal implant (100) using photolithography

5. 发明申请

WO2006116137A2 ARTIFICIAL CORNEA 审中-公开
标题翻译：人造石
公开(公告)号：WO2006116137A2
公开(公告)日：2006-11-02
申请号：PCT/US2006015173
申请日：2006-04-21
申请人： UNIV LELAND STANFORD JUNIOR , MYUNG DAVID , TA CHRISTOPHER , FAROOQUI NABEEL , CURTIS FRANK W , KOH WON-GUN , KO JUNGMIN , NOOLANDI JAAN , CARRASCO MICHAEL R
发明人： MYUNG DAVID , TA CHRISTOPHER , FAROOQUI NABEEL , CURTIS FRANK W , KOH WON-GUN , KO JUNGMIN , NOOLANDI JAAN , CARRASCO MICHAEL R
IPC分类号： A61K35/30 , A61F2/14
CPC分类号： A61F2/142 , A61F2/15 , A61K35/12
摘要： The present invention provides an artificial corneal implant having an optically clear central core and a porous, hydrophilic, biocompatible skirt peripheral to the central core. In one embodiment, the central core is made of an interpenetrating double network hydrogel and the skirt is made of poly(2-hydroxy ethyl acrylate) (PHEA). In another embodiment, both the central core and the skirt are made of interpenetrating double network hydrogels. The artificial corneal implant may also have an interdiffusion zone in which the skirt component is interpenetrated with the core component, or vice versa. In a preferred embodiment, biomolecules are linked to the skirt, central core or both. These biomolecules may be any type of biomolecule, but are preferably biomolecules that support epithelial and/or fibroblast cell survival and growth. Preferably, the biomolecules are linked in a spatially selective manner. The present invention also provides a method of making an artificial corneal implant using photolithography.
摘要翻译：本发明提供了一种人造角膜植入物，其具有光学透明的中心纤芯和围绕中心纤芯的多孔，亲水的，生物相容的裙部。在一个实施方案中，中心芯由互穿双网络水凝胶制成，裙部由聚（2-羟乙基丙烯酸酯）（PHEA）制成。在另一个实施例中，中心芯和裙部均由互穿双网络水凝胶制成。人造角膜植入物还可以具有相互扩散区域，其中裙部组件与芯部件互穿，反之亦然。在优选的实施方案中，生物分子连接到裙部，中心芯或两者。这些生物分子可以是任何类型的生物分子，但优选支持上皮和/或成纤维细胞存活和生长的生物分子。优选地，生物分子以空间选择性方式连接。本发明还提供了一种使用光刻制造人造角膜植入物的方法。

6. 发明申请

WO2006042272A2 ARTIFICIAL CORNEAL IMPLANT 审中-公开
标题翻译：人造牙科植入物
公开(公告)号：WO2006042272A2
公开(公告)日：2006-04-20
申请号：PCT/US2005/036648
申请日：2005-10-05
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , MYUNG, David , NOOLANDI, Jaan , SMITH, Alan, J. , FRANK, Curtis, W. , TA, Christopher , HU, Yin , KOH, Won-Gun , CARRASCO, Michael, R.
发明人： MYUNG, David , NOOLANDI, Jaan , SMITH, Alan, J. , FRANK, Curtis, W. , TA, Christopher , HU, Yin , KOH, Won-Gun , CARRASCO, Michael, R.
IPC分类号： A61K35/30 , A61F2/14
CPC分类号： A61K35/44 , A61F2/142 , A61F2/145 , A61L27/26 , A61L27/3804 , A61L27/3813 , A61L27/3839 , A61L27/52 , A61L27/54 , A61L2300/25 , A61L2300/252 , A61L2300/602 , A61L2430/16 , C12N5/0621 , C12N2533/30 , C08L33/08 , C08L71/02
摘要： A material that can be applied as implants designed to artificially replace or augment the cornea, such as an artificial cornea, corneal onlay, or corneal inlay (intrastromal lens) is provided. The artificial corneal implant has a double network hydrogel with a first network interpenetrated with a second network. The first network and the second network are based on biocompatible polymers. At least one of the network polymers is based on a hydrophilic polymer. The artificial cornea or implant has epithelialization promoting biomolecules that are covalently linked to the surface of the double network hydrogel using an azide-active-ester chemical linker. Corneal epithelial cells or cornea-derived cells are adhered to the biomolecules. The double network has a physiologic diffusion coefficient to allow passage of nutrients to the adhered cells.
摘要翻译：提供了可以作为植入物被应用于人造地替代或增加角膜的材料，例如人造角膜，角膜镶嵌物或角膜嵌体（体内镜片）。人造角膜植入物具有双网络水凝胶，其中第一网络与第二网络互穿。第一个网络和第二个网络是基于生物相容的聚合物。至少一种网状聚合物是基于亲水性聚合物。人造角膜或植入物具有上皮促进生物分子，其使用叠氮化物 - 活性酯化学接头共价连接到双网络水凝胶的表面。角膜上皮细胞或角膜衍生细胞粘附于生物分子。双网络具有生理扩散系数，以允许营养物质通过粘附细胞。

7. 发明申请

WO2020076991A1 ENGINEERED FIBROBLAST GROWTH FACTOR VARIANTS COMBINED WITH ENGINEERED HEPATOCYTE GROWTH FACTOR VARIANTS FOR TREATMENT 审中-公开
公开(公告)号：WO2020076991A1
公开(公告)日：2020-04-16
申请号：PCT/US2019/055453
申请日：2019-10-09
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , COCHRAN, Jennifer , MYUNG, David
发明人： COCHRAN, Jennifer , MYUNG, David
IPC分类号： A61P27/02 , A61K38/18 , C12N15/09
摘要： The present invention provides polypeptide variants for use in treatment, in particular variants of fibroblast growth factor (FGF) and variants of hepatocyte growth factor (HGF) for use in combination to treat corneal epithelial defects (PCEDs) and/or corneal neovascularization.

8. 发明申请

WO2007133266A2 INTERPENETRATING POLYMER NETWORK HYDROGEL CORNEAL PROSTHESIS 审中-公开
标题翻译：互聚聚合物网络水力发电机
公开(公告)号：WO2007133266A2
公开(公告)日：2007-11-22
申请号：PCT/US2006/047878
申请日：2006-12-14
申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY , MYUNG, David , TA, Christopher , FRANK, Curtis, W. , KOH, Won-gun , NOOLANDI, Jaan
发明人： MYUNG, David , TA, Christopher , FRANK, Curtis, W. , KOH, Won-gun , NOOLANDI, Jaan
IPC分类号： H01Q1/38
CPC分类号： C12N5/0621 , A61F2/142 , A61F2/15 , A61L27/00 , A61L27/26 , A61L27/52 , A61L27/54 , A61L2300/214 , A61L2300/23 , A61L2300/252 , A61L2300/258 , A61L2300/414 , A61L2430/16 , C12N2533/30 , C12N2533/54 , C08L71/02 , C08L33/08
摘要： The present invention provides materials that have high glucose and oxygen permeability, strength, water content, and resistance to protein adsorption. The materials include an interpenetrating polymer network (IPN) hydrogel that is coated with biomolecules. The IPN hydrogels include two interpenetrating polymer networks. The first polymer network is based on a hydrophilic telechelic macromonomer. The second polymer network is based on a hydrophilic monomer. The hydrophilic monomer is polymerized and cross-linked to form the second polymer network in the presence of the first polymer network. In a preferred embodiment, the hydrophilic telechelic macromonomer is PEG-diacrylate or PEG-dimethacrylate and the hydrophilic monomer is an acrylic-based monomer. Any biomolecules may be linked to the IPN hydrogels, but are preferably biomolecules that support the growth of cornea-derived cells. The material is designed to serve as a corneal prosthesis.
摘要翻译：本发明提供具有高葡萄糖和透氧性，强度，含水量和耐蛋白质吸附性的材料。这些材料包括涂覆有生物分子的互穿聚合物网络（IPN）水凝胶。 IPN水凝胶包括两个互穿聚合物网络。第一个聚合物网络是基于亲水的遥爪大分子单体。第二聚合物网络基于亲水性单体。在第一聚合物网络的存在下，亲水单体聚合并交联以形成第二聚合物网络。在优选的实施方案中，亲水遥爪大分子单体是PEG-二丙烯酸酯或PEG-二甲基丙烯酸酯，亲水性单体是丙烯酸类单体。任何生物分子可以连接到IPN水凝胶，但优选是支持角膜衍生细胞生长的生物分子。该材料设计用作角膜假体。

9. 发明申请

WO2012096997A2 ORTHOPEDIC IMPLANTS HAVING GRADIENT POLYMER ALLOYS 审中-公开
标题翻译：具有梯度聚合物合金的对称植入物
公开(公告)号：WO2012096997A2
公开(公告)日：2012-07-19
申请号：PCT/US2012020828
申请日：2012-01-10
申请人： BIOMIMEDICA INC , MYUNG DAVID , JAASMA MICHAEL J , KOURTIS LAMPROS , ROBERTS JEFFREY G , HARTDEGEN VERNON
发明人： MYUNG DAVID , JAASMA MICHAEL J , KOURTIS LAMPROS , ROBERTS JEFFREY G , HARTDEGEN VERNON
IPC分类号： A61L27/14 , A61F2/30 , A61L27/04
CPC分类号： A61L27/56 , A61F2/32 , A61F2/42 , A61F2002/30004 , A61F2002/30065 , A61F2002/30673 , A61F2002/30757 , A61L27/26 , A61L2430/02 , F04C2270/0421
摘要： Orthopedic implants having a bone interface member and a water swellable IPN or semi-IPN with a stiffness, hydration, and/or compositional gradient from one side to the other and physically attached to the bone interface member. The invention also includes an orthopedic implant system including an implant that may conform to a bone surface and a joint capsule. The invention also includes orthopedic implants with water swellable IPN or semi-IPNs including a hydrophobic thermoset or thermoplastic polymer first network and an ionic polymer second network, joint capsules, labral components, and bone interface members shaped to conform to a bone surface. The invention also includes a method of inserting an orthopedic implant having a metal portion and a flexible polymer portion into a joint, including inserting the implant in a joint in a first shape and changing the implant from a first shape to a second shape to conform to a shape of a bone.
摘要翻译：矫形植入物具有骨界面构件和具有从一侧到另一侧的刚度，水合和/或组成梯度的水膨胀性IPN或半IPN，并且物理附接到骨界面构件。本发明还包括矫形植入物系统，其包括可以符合骨表面和关节囊的植入物。本发明还包括具有水溶胀性IPN或半IPN的矫形植入物，其包括疏水性热固性或热塑性聚合物第一网络和离子聚合物第二网络，关节胶囊，唇部组分和成形为符合骨表面的骨界面构件。本发明还包括将具有金属部分和柔性聚合物部分的整形外科植入体插入到关节中的方法，包括将植入物插入第一形状的关节中并将植入物从第一形状改变为第二形状以符合骨的形状。

10. 发明申请

WO2009117737A3 METHODS, DEVICES AND COMPOSITIONS FOR ADHERING HYDRATED POLYMER IMPLANTS TO BONE 审中-公开
标题翻译：方法，装置和组合物，用于将水合的聚合物植入物粘合到骨中
公开(公告)号：WO2009117737A3
公开(公告)日：2010-11-04
申请号：PCT/US2009037979
申请日：2009-03-23
申请人： BIOMIMEDICA INC , MYUNG DAVID , JAASMA MICHAEL , KOURTIS LAMPROS
发明人： MYUNG DAVID , JAASMA MICHAEL , KOURTIS LAMPROS
IPC分类号： A61L27/50 , A61L27/18 , A61L27/34 , A61L27/52
CPC分类号： A61L33/0094 , A61L27/34 , A61L27/50 , A61L33/068 , A61L2400/18 , C08L75/04
摘要： A method of attaching an implant to a bone, the implant comprising a hydrated polymer comprising a lubricious hydrated surface and an attachment surface comprising accessible chemical functional groups. The method includes the steps of treating the implant or the bone with an isocyanate-containing compound; placing the attachment surface in apposition to the bone; and allowing the isocyanate-containing compound to cure to bond the implant to the bone. The invention also includes a medical implant having a hydrated polymer comprising an attachment surface comprising a thermoplastic material, the hydrated polymer having an interpenetrating polymer network with at least two polymers, the hydrated polymer having a low coefficient of friction on at least one surface.
摘要翻译：一种将植入物附着到骨骼上的方法，所述植入物包括包含光滑水合表面的水合聚合物和包含可接近的化学官能团的附着表面。该方法包括用含异氰酸酯的化合物处理植入物或骨骼的步骤; 将附着表面放置在骨骼上; 并允许含异氰酸酯的化合物固化以将植入物粘合到骨上。本发明还包括具有包含热塑性材料的附着表面的水合聚合物的医用植入物，所述水合聚合物具有至少两种聚合物的互穿聚合物网络，所述水合聚合物在至少一个表面上具有低摩擦系数。

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