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公开(公告)号：US06875427B1
公开(公告)日：2005-04-05
申请号：US09973332
申请日：2001-10-09
CPC分类号： A61L31/044 , A61K38/39 , A61L24/001 , A61L24/102 , A61L31/14
摘要： Consistent with the present invention, tissue adhesive compositions and an associated laser exposure system are provided for bonding or sealing biological tissues. The compositions are comprised of chemically derivatized soluble collagen which is formulated to concentrations ranging from 300 mg/ml (30%) to 800 mg/ml (80%) collagen protein. In particular, Type I collagen, for example, is first prepared by extraction from bovine or porcine hide and purified. The collagen preparations are then chemically derivatized with sulfhydryl reagents to improve cohesive strength and with secondary derivatizing agents, such as carboxyl groups, to improve the adhesive strength of the solder to the tissue. The compositions are then formed into viscous solutions, gels or solid films, which when exposed to energy generated from an infrared laser, for example, undergo thermally induced phase transitions. Solid or semi-solid protein compositions become less viscous enabling the high concentration protein to penetrate the interstices of treated biological tissue or to fill voids in tissue. As thermal energy is released into the surrounding environment, the protein compositions again become solid or semi-solid, adhering to the treated tissue or tissue space.
摘要翻译： 根据本发明，提供组织粘合剂组合物和相关联的激光曝光系统用于粘合或密封生物组织。 组合物由化学衍生的可溶性胶原组成，其被配制成浓度范围为300mg / ml（30％）至800mg / ml（80％））的胶原蛋白。 特别地，例如，I型胶原首先通过从牛或猪皮提取而纯化而制备。 然后将胶原蛋白制剂用巯基试剂进行化学衍生化，以提高内聚强度，并与二级衍生剂（如羧基）一起提高焊料对组织的粘合强度。 然后将组合物形成粘稠溶液，凝胶或固体膜，当暴露于由红外激光产生的能量时，例如经历热诱导相变。 固体或半固体蛋白质组合物变得粘稠，使得高浓度蛋白质能够渗透经处理的生物组织的间隙或填充组织中的空隙。 随着热能释放到周围环境中，蛋白质组合物再次变得固体或半固体，粘附到处理过的组织或组织空间。
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公开(公告)号：US06780840B1
公开(公告)日：2004-08-24
申请号：US09973263
申请日：2001-10-09
IPC分类号： A61K3800
CPC分类号： A61B18/22 , A61B17/00491 , A61B2017/0007 , A61B2017/00084 , A61B2017/005 , A61B2017/00508 , A61B2017/00517 , A61L24/102
摘要： Consistent with the present invention, tissue adhesive compositions and an associated laser exposure system are provided for bonding or sealing biological tissues. The compositions are comprised of chemically derivatized soluble collagen which is formulated to concentrations ranging from 300 mg/ml (30%) to 800 mg/ml (80%) collagen protein. In particular, Type I collagen, for example, is first prepared by extraction from bovine or porcine hide and purified. The collagen preparations are then chemically derivatized with sulfhydryl reagents to improve cohesive strength and with secondary derivatizing agents, such as carboxyl groups, to improve the adhesive strength of the solder to the tissue. The compositions are then formed into viscous solutions, gels or solid films, which when exposed to energy generated from an infrared laser, for example, undergo thermally induced phase transitions. Solid or semi-solid protein compositions become less viscous enabling the high concentration protein to penetrate the interstices of treated biological tissue or to fill voids in tissue. As thermal energy is released into the surrounding environment, the protein compositions again become solid or semi-solid, adhering to the treated tissue or tissue space.
摘要翻译： 根据本发明，提供组织粘合剂组合物和相关联的激光曝光系统用于粘合或密封生物组织。 组合物由化学衍生的可溶性胶原组成，其被配制成浓度范围为300mg / ml（30％）至800mg / ml（80％））的胶原蛋白。 特别地，例如，首先通过从牛或猪皮提取而制备I型胶原并纯化。 然后将胶原蛋白制剂用巯基试剂进行化学衍生，以提高内聚强度，并与二级衍生剂（如羧基）一起提高焊料对组织的粘合强度。 然后将组合物形成粘稠溶液，凝胶或固体膜，当暴露于由红外激光产生的能量时，例如经历热诱导相变。 固体或半固体蛋白质组合物变得粘稠，使得高浓度蛋白质能够渗透经处理的生物组织的间隙或填充组织中的空隙。 随着热能释放到周围环境中，蛋白质组合物再次变得固体或半固体，粘附到处理过的组织或组织空间。
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公开(公告)号：US06773699B1
公开(公告)日：2004-08-10
申请号：US09973385
申请日：2001-10-09
IPC分类号： A61K3800
CPC分类号： A61B18/22 , A61B17/00491 , A61B2017/0007 , A61B2017/00084 , A61B2017/005 , A61B2017/00508 , A61B2017/00517 , A61L31/044
摘要： Consistent with the present invention, tissue adhesive compositions and an associated laser exposure system are provided for bonding or sealing biological tissues. The compositions are comprised of chemically derivatized soluble collagen which is formulated to concentrations ranging from 300 mg/ml (30%) to 80 mg/ml (80%) collagen protein. In particular, Type I collagen, for example, is first prepared by extraction from bovine or porcine hide and purified. The collagen preparations are then chemically derivatized with sulfhydryl reagents to improve cohesive strength and with secondary derivatizing agents, such as carboxyl groups, to improve the adhesive strength of the solder to the tissue. The compositions are then formed into viscous solutions, gels or solid films which are used to encapsulate structural components such as a cojoinal network or mesh. The resultant patch which when exposed to energy generated from an infrared laser, for example, undergo thermally induced phase transitions. Solid or semi-solid protein compositions become less viscous enabling the high concentration protein to penetrate the interstices of treated biological tissue or to fill voids in tissue. As thermal energy is released into the surrounding environment, the protein compositions again become solid or semi-solid, adhering to the treated tissue or tissue space and are reinforced by the embedded cojoinal network or mesh.
摘要翻译： 根据本发明，提供组织粘合剂组合物和相关联的激光曝光系统用于粘合或密封生物组织。 组合物由化学衍生的可溶性胶原组成，其被配制成浓度范围为300mg / ml（30％）至80mg / ml（80％））的胶原蛋白。 特别地，例如，I型胶原首先通过从牛或猪皮提取而纯化而制备。 然后将胶原蛋白制剂用巯基试剂进行化学衍生化，以提高内聚强度，并与二级衍生剂（如羧基）一起提高焊料对组织的粘合强度。 然后将组合物形成粘稠溶液，凝胶或固体膜，其用于包封结构组分如共同网络或网状物。 例如，当暴露于由红外激光器产生的能量时，产生的贴片经历热诱导相变。 固体或半固体蛋白质组合物变得粘稠，使得高浓度蛋白质能够渗透经处理的生物组织的间隙或填充组织中的空隙。 随着热能释放到周围环境中，蛋白质组合物再次变成固体或半固体，粘附到经处理的组织或组织空间，并通过嵌入的共同网络或网来加强。
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公开(公告)号：US06939364B1
公开(公告)日：2005-09-06
申请号：US09973335
申请日：2001-10-09
CPC分类号： A61B18/22 , A61B17/00491 , A61B2017/0007 , A61B2017/00084 , A61B2017/005 , A61B2017/00508 , A61B2017/00517
摘要： Consistent with the present invention, tissue adhesive compositions and an associated laser exposure system are provided for bonding or sealing biological tissues. The compositions are comprised of chemically derivatized soluble collagen which is formulated to concentrations ranging from 300 mg/ml (30%) to 800 mg/ml (80%) collagen protein. In particular, Type I collagen, for example, is first prepared by extraction from bovine or porcine hide and purified. The collagen preparations are then chemically derivatized with sulfhydryl reagents to improve cohesive strength and with secondary derivatizing agents, such as carboxyl groups, to improve the adhesive strength of the solder to the tissue. The compositions are then formed into viscous solutions, gels or solid films, which when exposed to energy generated from an infrared laser, for example, undergo thermally induced phase transitions. Solid or semi-solid protein compositions become less viscous enabling the high concentration protein to penetrate the interstices of treated biological tissue or to fill voids in tissue. As thermal energy is released into the surrounding environment, the protein compositions again become solid or semi-solid, adhering to the treated tissue or tissue space.
摘要翻译： 根据本发明，提供组织粘合剂组合物和相关联的激光曝光系统用于粘合或密封生物组织。 组合物由化学衍生的可溶性胶原组成，其被配制成浓度范围为300mg / ml（30％）至800mg / ml（80％））的胶原蛋白。 特别地，例如，I型胶原首先通过从牛或猪皮提取而纯化而制备。 然后将胶原蛋白制剂用巯基试剂进行化学衍生化，以提高内聚强度，并与二级衍生剂（如羧基）一起提高焊料对组织的粘合强度。 然后将组合物形成粘稠溶液，凝胶或固体膜，当暴露于由红外激光产生的能量时，例如经历热诱导相变。 固体或半固体蛋白质组合物变得粘稠，使得高浓度蛋白质能够渗透经处理的生物组织的间隙或填充组织中的空隙。 随着热能释放到周围环境中，蛋白质组合物再次变得固体或半固体，粘附到处理过的组织或组织空间。
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5.发明授权Processing animal tissues by decellularizing, increasing surface area and acylating 有权通过脱细胞处理动物组织，增加表面积和酰化公开(公告)号：US06743435B2
公开(公告)日：2004-06-01
申请号：US09941438
申请日：2001-08-28
IPC分类号： A61F200
摘要： Methods are provided for processing and dispersing animal tissues that involve exposing processed (e.g., decellularized) tissue to an acylating agent, wherein the ratio of acylating agent to wet tissue weight is about 0.003:1 or less. Preferably, decellularized tissue is exposed to an amount of the acylating agent of about 0.1% to about 0.3% of wet tissue weight for a time ranging from about 30 seconds to about 10 minutes. A dispersed tissue matrix is produced that has a high degree of resistance to digestion by non-collagenase proteases, such as trypsin. In order to produce sufficiently high yields of these trypsin-resistant compositions, the processed tissue is preferably cryomilled to increase its surface area prior to acylation. The dispersed acylated decellularized tissue may be in the form of an injectable composition that can be introduced into tissue of a subject.
摘要翻译： 提供了用于处理和分散动物组织的方法，所述动物组织涉及将经处理（例如脱细胞化）组织暴露于酰化剂，其中酰化剂与湿组织重量的比例为约0.003:1或更低。 优选地，脱细胞组织暴露于大约0.1％至大约0.3％湿组织重量的酰基化剂，时间范围为约30秒至约10分钟。 产生分散的组织基质，其具有高抗非消化蛋白酶如胰蛋白酶的抗性。 为了产生足够高的这些胰蛋白酶抗性组合物的产量，处理过的组织优选被冷冻以在酰化之前增加其表面积。 分散的酰化脱细胞组织可以是可以引入受试者组织的可注射组合物的形式。
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6.发明授权Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom 失效生物相容的胶原反应产物和用作从其生产的医疗植入物的制品
公开(公告)号：US5480427A
公开(公告)日：1996-01-02
申请号：US278972
申请日：1994-07-19
申请人： Charles D. Kelman , Dale P. DeVore
发明人： Charles D. Kelman , Dale P. DeVore
CPC分类号： C08F289/00 , A61L27/24 , G02B1/043 , A61F2310/00365 , A61L2430/16 , Y10S128/08 , Y10S623/901
摘要： The present invention provides a biologically compatible collagenous reaction product comprising ethylenically unsaturated monomerically substituted collagen, the monomeric substituents being essentially free of nitrogen, e.g., methyacrylate, styrene, polyvinyl, ethylene. The collagenous reaction product can be polymerized, e.g., by exposure to UV irradiation, chemical agents or atmospheric oxygen, and molded to form useful medical implant articles. Methods of preparation are also provided.
摘要翻译： 本发明提供了一种生物相容的胶原反应产物，其包含烯属不饱和单体取代的胶原，单体取代基基本上不含氮，例如甲基丙烯酸酯，苯乙烯，聚乙烯基，乙烯。 可以例如通过暴露于UV照射，化学试剂或大气氧来聚合胶原反应产物，并模制以形成有用的医用植入物制品。 还提供了制备方法。
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公开(公告)号：US06299856B1
公开(公告)日：2001-10-09
申请号：US09497568
申请日：2000-02-03
申请人： Dale P. DeVore , Joel D. Magerman
发明人： Dale P. DeVore , Joel D. Magerman
IPC分类号： A61K5100
CPC分类号： A61K41/0095 , A61K51/08 , A61K51/088
摘要： Disclosed herein is a method for treating a malignancy in an animal by introducing into the animal a radioactive isotope, or stable element subsequently made radioactive, covalently linked to a collagen. Also disclosed herein are such radiolabeled collagen compositions.
摘要翻译： 本文公开了一种通过向动物中引入与胶原共价连接的放射性同位素或随后放射性的稳定元件来治疗动物的恶性肿瘤的方法。 本文还公开了这样的放射性标记的胶原组合物。
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公开(公告)号：US5631243A
公开(公告)日：1997-05-20
申请号：US365167
申请日：1994-12-28
申请人： Charles D. Kelman , Dale P. DeVore
发明人： Charles D. Kelman , Dale P. DeVore
IPC分类号： A61F2/14 , A61F9/00 , A61K9/08 , A61K31/715 , A61K47/36 , A61L31/04 , A61P27/02 , C07K14/78 , C08L89/06 , A61K31/725 , A61M31/00
CPC分类号： C07K14/78 , A61L31/041 , C08L89/06 , A61L2430/16 , Y10S514/801 , Y10S514/912
摘要： The present invention relates to a method of treating a patient with visco-surgery, particularly ocular visco-surgery, utilizing a collagen-based viscoelastic solution having a reversibly high viscosity. The invention also relates to collagen-based viscoelastic solutions which further include mucopolysaccarides or growth factors.
摘要翻译： 本发明涉及利用具有可逆高粘度的胶原蛋白基粘弹性溶液治疗患有粘膜手术的患者，特别是眼部粘膜手术的方法。 本发明还涉及进一步包括粘多糖或生长因子的基于胶原的粘弹性溶液。
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9.发明授权Method of making intraocular lenses with injectable collagen-based compositions 失效利用可注射胶原蛋白的组合物制造眼内透镜的方法
公开(公告)号：US5476515A
公开(公告)日：1995-12-19
申请号：US158019
申请日：1993-11-24
申请人： Charles D. Kelman , Dale P. DeVore
发明人： Charles D. Kelman , Dale P. DeVore
CPC分类号： A61L27/24 , A61F2/16 , A61F2/1616 , C08H1/06 , A61F2310/00365 , Y10S623/901
摘要： Injectable collagen-based compositions can be used in methods to fill a lens capsular sac, following lens extraction procedures, to form a new intraocular lens. Purified soluble or partially fibrillar collagen may be modified with acylating agents, sulfonating agents or combinations thereof to form a clear, transparent collagen composition having indices of refraction between about 1.2 to 1.6. The modified collagen may injected into a lens capsular sac to form an intraocular lens (IOL) in situ. The IOL is clear, transparent, resistant to epithelialization and is capable of accommodation. The collagen-based IOL produced by the method of the present invention may remain in its original viscous liquid state or may be polymerized into a soft gel. The collagen-based IOL may be used to replace diseased or natural lens to treat cataracts, presbyopia, myopia and hyperopia.
摘要翻译： 可注射的基于胶原的组合物可以用于填充镜片囊囊的方法，在镜片提取程序之后，形成新的眼内透镜。 可以用酰化剂，磺化剂或其组合来修饰纯化的可溶性或部分原纤维胶原，以形成折射率在约1.2至1.6之间的透明，透明的胶原组合物。 改性胶原蛋白可以注射到晶状体囊囊中以形成眼内晶状体（IOL）。 IOL是透明的，透明的，耐上皮化，并且能够适应。 通过本发明的方法制备的基于胶原的IOL可以保持其原始的粘性液体状态，或者可以聚合成软凝胶。 基于胶原的IOL可用于替代患病或天然晶状体以治疗白内障，老花眼，近视和远视。
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公开(公告)号：US5332802A
公开(公告)日：1994-07-26
申请号：US897562
申请日：1992-06-11
申请人： Charles D. Kelman , Dale P. DeVore
发明人： Charles D. Kelman , Dale P. DeVore
CPC分类号： C08H1/06 , A61L27/24 , C07K14/78 , A61F2310/00365 , A61K38/00 , Y10S128/08 , Y10S623/915
摘要： Production of a chemically modified, crosslinkable, telopeptide-containing, naturally crosslinked, solubilized collagen from tissue obtained from a sole human donor, for implanting in the same donor, by chemically modifying the tissue, e.g. by acylation and/or esterification, to form an autoimplantable, crosslinkable, telopeptide-containing, naturally crosslinked, collagen product, as a completely solubilized collagen solution, optionally of high index of refraction for correcting sight or as a partially solubilized collagen suspension; and use of the product for altering the condition of in situ tissue of the same human donor by autoimplantation, such as by crosslinking the product to form an implant device, by placing an effective amount of the product at the tissue site and crosslinking the product in situ, or by partially crosslinking the product and placing an effective amount thereof at the tissue site and optionally further crosslinking the product in situ.
摘要翻译： 通过化学修饰组织，例如通过化学修饰组织来生产由从唯一人供体获得的组织中经化学修饰的，可交联的，含端肽的天然交联的溶解胶原蛋白，用于植入同一供体。 通过酰化和/或酯化形成可自动移植的，可交联的，含有端肽的天然交联的胶原产品，作为完全溶解的胶原溶液，任选地具有高折射率以矫正视力或作为部分溶解的胶原悬浮液; 以及使用产品通过自动植入来改变相同人类供体的原位组织的状况，例如通过将产物交联以形成植入装置，通过将有效量的产物放置在组织部位并将产物交联 或通过将产物部分交联并将其有效量置于组织部位并任选地进一步原位交联产物。
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