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1. 发明公开

EP1642911A3 Hydrogel and method of making 审中-公开
标题翻译：水凝胶和其制备方法
公开(公告)号：EP1642911A3
公开(公告)日：2006-04-19
申请号：EP05025797.1
申请日：2000-09-28
申请人： Stoy, Vladimir A.
发明人： Stoy, Vladimir A.
IPC分类号： C08F8/12 , C08F220/44 , C08L33/20
CPC分类号： C08L33/20 , C08F8/06 , C08F8/12 , C08F8/30 , C08F2800/10 , C08F20/44
摘要： The present invention is a method of making acrylonitrile copolymers having multi block structure comprising acrylic acid, acryl amids and acrylamidine hydrophilic groups in hydrophilic blocks and residual nitrile groups in hydrophobic blocks, by partial hydrolysis of polyacrylonitrile to a predetermined hydrolysis conversion at which the hydrolysis is self terminating, by a process that improves quality and reduces product heterogeneity. It includes forming a first reaction mixture which includes polyacrylonitrile dissolved in an aqueous reactive solvent containing sodium thiocyanate; forming a second reaction mixture comprising a reaction catalyst of the general formula MY dissolved in an aqueous reactive solvent containing sodium thiocyanate; mixing the reaction mixtures of steps (a) and (b) above to form a master reaction mix; dividing the reaction mix into a plurality of physical reaction compartments so as to increase outer surface area relative to volume as compared to outer surface area of a single reaction compartment to enhance cooling efficiency and to reduce undesirable center core thermal effects; and, heating the divided master reaction mix to a predetermined reaction temperature range and maintaining the temperature range for a predetermined time sufficient for completion of a predetermined level of hydrolysis at which the resulting copolymer solution is substantially stable at ambient temperature. The invention also includes hydrogel products resulting from the method.

2. 发明公开

EP1642911A2 Hydrogel and method of making 审中-公开
标题翻译：水凝胶和制造方法
公开(公告)号：EP1642911A2
公开(公告)日：2006-04-05
申请号：EP05025797.1
申请日：2000-09-28
申请人： Stoy, Vladimir A.
发明人： Stoy, Vladimir A.
IPC分类号： C08F8/12 , C08F220/44 , C08L33/20
CPC分类号： C08L33/20 , C08F8/06 , C08F8/12 , C08F8/30 , C08F2800/10 , C08F20/44
摘要： The present invention is a method of making acrylonitrile copolymers having multi block structure comprising acrylic acid, acryl amids and acrylamidine hydrophilic groups in hydrophilic blocks and residual nitrile groups in hydrophobic blocks, by partial hydrolysis of polyacrylonitrile to a predetermined hydrolysis conversion at which the hydrolysis is self terminating, by a process that improves quality and reduces product heterogeneity. It includes forming a first reaction mixture which includes polyacrylonitrile dissolved in an aqueous reactive solvent containing sodium thiocyanate; forming a second reaction mixture comprising a reaction catalyst of the general formula MY dissolved in an aqueous reactive solvent containing sodium thiocyanate; mixing the reaction mixtures of steps (a) and (b) above to form a master reaction mix; dividing the reaction mix into a plurality of physical reaction compartments so as to increase outer surface area relative to volume as compared to outer surface area of a single reaction compartment to enhance cooling efficiency and to reduce undesirable center core thermal effects; and, heating the divided master reaction mix to a predetermined reaction temperature range and maintaining the temperature range for a predetermined time sufficient for completion of a predetermined level of hydrolysis at which the resulting copolymer solution is substantially stable at ambient temperature. The invention also includes hydrogel products resulting from the method.
摘要翻译：本发明是一种制备具有多嵌段结构的丙烯腈共聚物的方法，所述丙烯腈共聚物包含亲水性嵌段中的丙烯酸，丙烯酰胺和丙烯酰胺亲水基团以及疏水性嵌段中的残余腈基，通过将聚丙烯腈部分水解成预定的水解转化，通过改进质量和降低产品异质性的过程自我终止。它包括形成第一反应混合物，其包括溶解在含有硫氰酸钠的含水反应性溶剂中的聚丙烯腈; 形成第二反应混合物，所述第二反应混合物包含溶解在含有硫氰酸钠的含水反应性溶剂中的通式MY的反应催化剂; 混合上述步骤（a）和（b）的反应混合物以形成主反应混合物; 将反应混合物分成多个物理反应室，以便相对于单个反应室的外表面积增加外表面积以增强冷却效率并减少不希望的中心核热效应; 和将分开的主反应混合物加热到预定的反应温度范围并保持该温度范围足够的预定时间，以完成所得共聚物溶液在环境温度下基本稳定的预定水解水平。本发明还包括由该方法产生的水凝胶产品。

3. 发明公开

EP1231868A4 SPINAL NUCLEUS IMPLANT 有权
标题翻译：核植入脊柱
公开(公告)号：EP1231868A4
公开(公告)日：2010-01-06
申请号：EP00968536
申请日：2000-09-28
申请人： STOY VLADIMIR A
发明人： STOY VLADIMIR A
IPC分类号： A61F2/00 , A61F2/44 , A61L27/16 , A61L27/18 , A61L27/20 , A61L27/44 , A61L27/50 , A61L27/52
CPC分类号： A61L27/20 , A61F2/441 , A61F2/442 , A61F2002/30075 , A61F2002/4435 , A61F2002/444 , A61F2210/0061 , A61L27/16 , A61L27/18 , A61L27/44 , A61L27/50 , A61L27/52 , A61L2430/38 , C08L33/00 , C08L31/00 , C08L29/00 , C08L27/00 , C08L23/00 , C08L85/02 , C08L83/04 , C08L67/00 , C08L75/00

4. 发明授权

EP1231868B1 SPINAL NUCLEUS IMPLANT 有权
标题翻译：脊髓核植入物
公开(公告)号：EP1231868B1
公开(公告)日：2011-06-15
申请号：EP00968536.3
申请日：2000-09-28
申请人： Stoy, Vladimir A.
发明人： Stoy, Vladimir A.
IPC分类号： A61F2/44
CPC分类号： A61L27/20 , A61F2/441 , A61F2/442 , A61F2002/30075 , A61F2002/4435 , A61F2002/444 , A61F2210/0061 , A61L27/16 , A61L27/18 , A61L27/44 , A61L27/50 , A61L27/52 , A61L2430/38 , C08L33/00 , C08L31/00 , C08L29/00 , C08L27/00 , C08L23/00 , C08L85/02 , C08L83/04 , C08L67/00 , C08L75/00
摘要： The present invention is a spinal nucleus implant (21A) for replacement of at least a portion of nucleus pulposus tissue (13) removed from a spinal disc of a living vertebrate to restore function of the spinal disc (1) and related vertebral joint. The implant is an anisotropically swellable, biomimetic xerogel plastic, having a two phase structure with a hydrophobic phase having high crystallinity and low water content and with hydrophilic phase having low crystallinity and high water content and having negatively charged lubricious surface. The xerogel plastic is capable of rehydration and of osmotic movement of liquid therethrough in response to osmotic pressure change to thereby increase and decrease liquid content in its hydrated state. The present invention also relates to surgical implant procedures utilizing this spinal nucleus implant (21A).
摘要翻译：本发明是一种脊髓核植入物（21A），用于替代从活脊椎动物的脊椎盘移除的至少一部分髓核组织（13）以恢复脊椎盘（1）和相关椎关节的功能。植入物是各向异性溶胀的仿生干凝胶塑料，具有疏水相具有高结晶度和低含水量以及亲水相具有低结晶度和高含水量并且具有带负电的光滑表面的两相结构。响应于渗透压的变化，干凝胶塑料能够使液体再渗透并渗透液体，从而增加和减少其水合状态下的液体含量。本发明还涉及利用该脊髓核植入物（21A）的手术植入程序。

5. 发明公开

EP1232192A4 HYDROGEL AND METHOD OF MAKING 有权
标题翻译：水凝胶及其制备方法
公开(公告)号：EP1232192A4
公开(公告)日：2004-07-28
申请号：EP00968549
申请日：2000-09-28
申请人： STOY VLADIMIR A
发明人： STOY VLADIMIR A
IPC分类号： C08F8/12 , C08F220/44 , C08L33/20
CPC分类号： C08L33/20 , C08F8/06 , C08F8/12 , C08F8/30 , C08F2800/10 , C08F20/44
摘要： The present invention is a method of making acrylonitrile copolymers having multi block structure comprising acrylic acid, acryl amids and acrylamidine hydrophilic groups in hydrophilic blocks and residual nitrile groups in hydrophobic blocks, by partial hydrolysis of polyacrylonitrile to a predetermined hydrolysis conversion at which the hydrolysis is self terminating, by a process that improves quality and reduces product heterogeneity. It includes forming a first reaction mixture which includes polyacrylonitrile dissolved in an aqueous reactive solvent containing sodium thiocyanate; forming a second reaction mixture comprising a reaction catalyst of the general formula MY dissolved in an aqueous reactive solvent containing sodium thiocyanate; mixing the reaction mixtures of steps (a) and (b) above to form a master reaction mix; dividing the reaction mix into a plurality of physical reaction compartments so as to increase outer surface area relative to volume as compared to outer surface area of a single reaction compartment to enhance cooling efficiency and to reduce undesirable center core thermal effects; and, heating the divided master reaction mix to a predetermined reaction temperature range and maintaining the temperature range for a predetermined time sufficient for completion of a predetermined level of hydrolysis at which the resulting copolymer solution is substantially stable at ambient temperature. The invention also includes hydrogel products resulting from the method.

6. 发明公开

EP1232192A1 HYDROGEL AND METHOD OF MAKING 有权
标题翻译：水凝胶及其制备方法
公开(公告)号：EP1232192A1
公开(公告)日：2002-08-21
申请号：EP00968549.6
申请日：2000-09-28
申请人： Stoy, Vladimir A.
发明人： Stoy, Vladimir A.
IPC分类号： C08F8/12
CPC分类号： C08L33/20 , C08F8/06 , C08F8/12 , C08F8/30 , C08F2800/10 , C08F20/44
摘要： The present invention is a method of making acrylonitrile copolymers having multi block structure comprising acrylic acid, acryl amids and acrylamidine hydrophilic groups in hydrophilic blocks and residual nitrile groups in hydrophobic blocks, by partial hydrolysis of polyacrylonitrile to a predetermined hydrolysis conversion at which the hydrolysis is self terminating, by a process that improves quality and reduces product heterogeneity. It includes forming a first reaction mixture which includes polyacrylonitrile dissolved in an aqueous reactive solvent containing sodium thiocyanate; forming a second reaction mixture comprising a reaction catalyst of the general formula MY dissolved in an aqueous reactive solvent containing sodium thiocyanate; mixing the reaction mixtures of steps (a) and (b) above to form a master reaction mix; dividing the reaction mix into a plurality of physical reaction compartments so as to increase outer surface area relative to volume as compared to outer surface area of a single reaction compartment to enhance cooling efficiency and to reduce undesirable center core thermal effects; and, heating the divided master reaction mix to a predetermined reaction temperature range and maintaining the temperature range for a predetermined time sufficient for completion of a predetermined level of hydrolysis at which the resulting copolymer solution is substantially stable at ambient temperature. The invention also includes hydrogel products resulting from the method.

7. 发明公开

EP1231868A2 SPINAL NUCLEUS IMPLANT 有权
标题翻译：核植入脊柱
公开(公告)号：EP1231868A2
公开(公告)日：2002-08-21
申请号：EP00968536.3
申请日：2000-09-28
申请人： Stoy, Vladimir A.
发明人： Stoy, Vladimir A.
IPC分类号： A61F2/00
CPC分类号： A61L27/20 , A61F2/441 , A61F2/442 , A61F2002/30075 , A61F2002/4435 , A61F2002/444 , A61F2210/0061 , A61L27/16 , A61L27/18 , A61L27/44 , A61L27/50 , A61L27/52 , A61L2430/38 , C08L33/00 , C08L31/00 , C08L29/00 , C08L27/00 , C08L23/00 , C08L85/02 , C08L83/04 , C08L67/00 , C08L75/00
摘要： The present invention is a spinal nucleus implant (21A) for replacement of at least a portion of nucleus pulposus tissue (13) removed from a spinal disc of a living vertebrate to restore function of the spinal disc (1) and related vertebral joint. The implant is an anisotropically swellable, biomimetic xerogel plastic, having a two phase structure with a hydrophobic phase having high crystallinity and low water content and with hydrophilic phase having low crystallinity and high water content and having negatively charged lubricious surface. The xerogel plastic is capable of rehydration and of osmotic movement of liquid therethrough in response to osmotic pressure change to thereby increase and decrease liquid content in its hydrated state. The present invention also relates to surgical implant procedures utilizing this spinal nucleus implant (21A).

8. 发明申请

WO2009049568A2 STERILE AUTOLOGOUS, ALLOGENIC OR XENOGENIC IMPLANT AND THE METHOD OF ITS PRODUCTION 审中-公开
标题翻译：无菌自动，异源性或生殖植入物及其生产方法
公开(公告)号：WO2009049568A2
公开(公告)日：2009-04-23
申请号：PCT/CZ2008/000128
申请日：2008-10-17
申请人： BIO-SKIN, a.s. , DRUNECKY, Tomas , MATOUSKOVA, Eva , STEHLICEK, Petr , STOY, Vladimir , VESELY, Pavel
发明人： DRUNECKY, Tomas , MATOUSKOVA, Eva , STEHLICEK, Petr , STOY, Vladimir , VESELY, Pavel
CPC分类号： A61K38/39 , A61L27/3633 , A61L27/3691 , A61L27/38 , A61L27/3813 , A61L27/50 , A61L27/60 , A61L2430/40
摘要： The subject of the invention is a sterile, dehydrated acellular implant, which during its rehydration by water or bodily fluids displays anisotropic expansion and can act as a substrate for adhesion, migration and growth of live cells. Collagen structures of the transplant are at least partially denatured through the action of heat or organic solvents, such as lower aliphatic alcohols and ketones, which simultaneously act as preservative and sterilization agents, especially for certain types of viruses. The implant is sterilized by radiation while in an substantially dehydrated state, preferably by accelerated electrons. The transplant can be derived from various animal tissues, especially mammalian tissues, such as human or porcine tissues. The tissues suitable for the invention can be, for example, skin, placenta, pericardium, peritoneum, intestinal wall, tendon, blood vessel, etc. The implant is suitable for use in human and veterinary medicine, for instance as a temporary wound and burn cover, for the repair, substitution and regeneration of tissues, and also as a substrate for laboratory cell cultivation.
摘要翻译：本发明的主题是无菌，脱水的无细胞植入物，其在水或体液的再水化过程中显示各向异性膨胀，并且可以作为活细胞粘附，迁移和生长的底物。移植物的胶原结构通过热或有机溶剂（例如低级脂族醇和酮）的作用至少部分变性，其同时用作防腐剂和消毒剂，特别是对于某些类型的病毒。植入物在处于基本脱水状态时通过放射线灭菌，优选通过加速的电子灭菌。移植可衍生自各种动物组织，特别是哺乳动物组织，如人或猪组织。适用于本发明的组织可以是例如皮肤，胎盘，心包膜，腹膜，肠壁，肌腱，血管等。植入物适合用于人和兽医学，例如作为临时伤口和烧伤覆盖，用于组织的修复，替代和再生，以及用作实验室细胞培养的底物。

9. 发明申请

WO2001022902A9 SPINAL NUCLEUS IMPLANT 审中-公开
公开(公告)号：WO2001022902A9
公开(公告)日：2001-04-05
申请号：PCT/US2000/027027
申请日：2000-09-28
申请人： STOY, Vladimir, A.
发明人： STOY, Vladimir, A.
IPC分类号： A61F2/00 , A61F2/44 , A61L27/16 , A61L27/18 , A61L27/20 , A61L27/44 , A61L27/50 , A61L27/52
摘要： The present invention is a spinal nucleus implant (21A) for replacement of at least a portion of nucleus pulposus tissue (13) removed from a spinal disc of a living vertebrate to restore function of the spinal disc (1) and related vertebral joint. The implant is an anisotropically swellable, biomimetic xerogel plastic, having a two phase structure with a hydrophobic phase having high crystallinity and low water content and with hydrophilic phase having low crystallinity and high water content and having negatively charged lubricious surface. The xerogel plastic is capable of rehydration and of osmotic movement of liquid therethrough in response to osmotic pressure change to thereby increase and decrease liquid content in its hydrated state. The present invention also relates to surgical implant procedures utilizing this spinal nucleus implant (21A).

10. 发明申请

WO2004064693A1 HYDROGEL-BASED PROSTHETIC DEVICE FOR REPLACING AT LEAST A PART OF THE NUCLEUS OF A SPINAL DISC 审中-公开
标题翻译：用于替代脊髓核的一部分的基于水凝胶的前置装置
公开(公告)号：WO2004064693A1
公开(公告)日：2004-08-05
申请号：PCT/US2003/001434
申请日：2003-01-16
申请人： REPLICATION MEDICAL, INC. , STOY, Vladimir, A.
发明人： STOY, Vladimir, A.
IPC分类号： A61F2/44
CPC分类号： A61F2/442 , A61F2002/30014 , A61F2002/30016 , A61F2002/30075 , A61F2002/30125 , A61F2002/30324 , A61F2002/30448 , A61F2002/30563 , A61F2002/30971 , A61F2002/444 , A61F2002/4495 , A61F2210/0061 , A61F2220/005 , A61F2230/0008 , A61F2250/0018 , A61F2250/0019 , A61F2250/0036 , A61F2310/00365
摘要： The present invention is a prosthetic for replacement of at least a part of the nucleus of a intravertebral disc. The prosthetic device is composed of at least two substantially parallel soft layers (13, 15, 17, 19) of an elastically deformable hydrogel and at least one more rigid layer (21, 23, 25), the more rigid layer having less compressibility than the soft layers, being adjacent to the soft layers, and firmly attached to them. In some embodiments, the soft layers have the same thickness and composition. Typically, the prosthesis has more than one more rigid layer and these more rigid layers have the same thickness and composition. The number of soft layers is usually one more than the number of more rigid layers, with, e.g., at least three soft layers. The invention also includes a method of prosthesis production, which involves prefabricating soft and more rigid layers; stacking at least two prefabricated soft and at least one prefabricated more rigid layer in a substantially parallel fashion into their final form, and, permitting the layers to firmly connect to one another by mutual interaction. In this method, at least one type of the layers is prefabricated in the dehydrated state, which is done by dehydrating stretched foil in an apparatus preventing its contraction and thereby decreasing its area. There is at least partial dehydration of the prosthesis under pressure applied in a direction tangent to the planes of the layers. In preferred embodiments, while in the state of almost full dehydration, the implant is sterilized using ionizing radiation or a gaseous chemical agent, after which it is partially rehydrated within a sterile wrapper using water vapor.
摘要翻译：本发明是用于替代椎间盘的核的至少一部分的假体。假体装置由至少两个基本上平行的可弹性变形的水凝胶和至少一个更刚性层（21,23,25）的软层（13,15,17,19）组成，更刚性层具有比软层，与软层相邻，并牢固地附着在它们上。在一些实施例中，软层具有相同的厚度和组成。通常，假体具有多于一个的刚性层，并且这些更刚性的层具有相同的厚度和组成。软层的数量通常比刚性层的数量多一个，例如至少三个软层。本发明还包括假体生产方法，其涉及预制柔性和更刚性的层; 将至少两个预制的软的和至少一个预制的更刚性的层以基本上平行的方式堆叠成其最终形式，并且允许层通过相互作用彼此牢固地连接。在这种方法中，至少一种类型的层是在脱水状态下预制的，这是通过在防止其收缩的装置中脱水拉伸的箔而由此减小其面积而完成的。在与层的平面相切的方向施加压力的假体至少部分脱水。在优选的实施方案中，当处于几乎完全脱水的状态时，使用电离辐射或气体化学试剂对植入物进行灭菌，然后使用水蒸汽在无菌包装内将其部分再水化。

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