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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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2.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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3.发明授权
公开(公告)号：US5861486A
公开(公告)日：1999-01-19
申请号：US602922
申请日：1996-02-16
IPC分类号： A61F9/008 , A61F9/01 , A61L26/00 , A61L31/04 , C07K14/78 , C08H1/06 , C08L89/06 , A61K38/17 , A61K38/39
CPC分类号： C08H1/06 , A61F9/00819 , A61L26/0033 , A61L31/044 , C07K14/78 , C08L89/06 , A61F2009/00872 , A61F9/00804
摘要： A method of smoothing irregular corneal surfaces and removing protuberances from corneal surfaces by photoablative eximer laser keratectomy is provided. Collagen compositions for use in making collagen modulators useful in photoablative procedures are described. These compositions are applied to irregular corneal surfaces in sufficient amounts to at least fill in depressions or other irregularities on a corneal surface and are converted into a modulator, as a gel or polymerized film, prior to photoablation. The collagen modulators facilitate the photoablative smoothing of irregular corneal surfaces and protect adjacent corneal tissue from undesired photoablation.
摘要翻译： 提供了一种通过光烧伤激光角膜切除术来平滑不规则角膜表面和从角膜表面去除突起的方法。 描述了用于制备用于光蚀刻程序的胶原调节剂的胶原组合物。 将这些组合物以足够的量应用于不规则的角膜表面，至少填充角膜表面上的凹陷或其它不规则物，并在光消除之前转化为调制剂，作为凝胶或聚合膜。 胶原调节剂促进不规则角膜表面的光蚀刻平滑，并保护邻近角膜组织免受不希望的光消融。
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公开(公告)号：US5840848A
公开(公告)日：1998-11-24
申请号：US778467
申请日：1997-01-03
摘要： An method is disclosed for removing Type I collagen-containing tissue adjoining Type II collagen-containing animal tissue comprising treatment of unprocessed Type II collagen-containing tissue in an acidic solution in the presence of an acid proteinase and subjecting the mixture to moderate agitation for a period of time sufficient to cause digestion or separation of the Type I collagen-containing tissue from the Type II collagen-containing tissue. Also disclosed are methods for removing proteoglycans from Type II collagen-containing tissue.
摘要翻译： 公开了一种用于去除含有II型胶原的动物组织的含I型胶原的组织的方法，包括在酸性蛋白酶存在下在酸性溶液中处理未加工的含II型胶原蛋白的组织，并对该混合物进行适度搅拌 足以引起含有I型胶原的组织从含有I型胶原的组织消化或分离的时间。 还公开了从含II型胶原的组织中去除蛋白聚糖的方法。
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5.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：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：US06448378B2
公开(公告)日：2002-09-10
申请号：US09735182
申请日：2000-12-12
IPC分类号： A61K3817
CPC分类号： A61K9/7007
摘要： Disclosed herein are collagen films which rapidly dissolve at 35° C. Also disclosed are methods for the preparation of the collagen films and their use as a vehicle for delivering a dose of therapeutic compound to a specific tissue site.
摘要翻译： 本文公开了在35℃下快速溶解的胶原膜。还公开了制备胶原薄膜的方法及其作为将剂量的治疗化合物递送至特定组织部位的载体的用途。
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8.发明授权
公开(公告)号：US5354336A
公开(公告)日：1994-10-11
申请号：US31665
申请日：1993-03-15
申请人： Charles D. Kelman , Dale P. DeVore
发明人： Charles D. Kelman , Dale P. DeVore
CPC分类号： C08H1/06 , A61L24/102 , C09J189/06 , A61F9/0079 , A61F9/00819
摘要： The present invention relates to a method for bonding soft tissues. The method comprises the steps of (a) applying a polymerizable collagen composition onto at least portion of a surface of at least one of a first tissue and a second tissue, (b) exposing the polymerizable collagen composition to an initiator so as to initiate polymerization of the polymerizable collagen composition and (c) contacting the first tissue and the second tissue so that the exposed polymerizable collagen composition forms a bond between the first tissue and the second tissue.
摘要翻译： 本发明涉及一种粘合软组织的方法。 该方法包括以下步骤：（a）将可聚合胶原蛋白组合物施加到至少一个第一组织和第二组织的表面的至少部分上，（b）将可聚合的胶原组合物暴露于引发剂以引发聚合 的可聚合胶原组合物和（c）使第一组织和第二组织接触，使得暴露的可聚合胶原蛋白组合物在第一组织和第二组织之间形成结合。
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公开(公告)号：US4969912A
公开(公告)日：1990-11-13
申请号：US157638
申请日：1988-02-18
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.
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公开(公告)号：US4920104A
公开(公告)日：1990-04-24
申请号：US194187
申请日：1988-05-16
CPC分类号： C08B37/0072 , A61K9/0048 , A61L31/042 , A61L2430/16 , Y10S514/912
摘要： Solutions of sodium hyaluronate in physiological saline with a kinematic viscosity of from 45,000 to 64,000 cSt. are found to effect a smaller increase in post-operative intra-ocular pressure following use as an aid in opthalmological surgery, when the weight average molecular weight of the hyaluronate is within the range of from 1 to 2 million Daltons.
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