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公开(公告)号：US20150238659A1
公开(公告)日：2015-08-27
申请号：US14707970
申请日：2015-05-08
CPC分类号： A61F2/2415 , A61F2/0095 , A61F2/24 , A61F2/2412 , A61F2/2418 , A61L27/3604 , A61L27/3625 , A61L27/3629 , A61L27/3687 , A61L27/3691 , A61L27/507 , A61L2400/02 , A61L2430/20
摘要： A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification. The method includes applying a calcification mitigant such as a capping agent or an antioxidant to the tissue to specifically inhibit oxidation in tissue. Also, the method can be used to inhibit oxidation in dehydrated tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the oxidation and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde capping agent prior to dehydration and sterilization.
摘要翻译： 用于植入物或组装的生物假体心脏瓣膜中用于减少体内钙化的生物假体组织的治疗。 该方法包括将钙化缓解剂如封端剂或抗氧化剂施用于组织以特异性抑制组织中的氧化。 此外，该方法可用于抑制脱水组织中的氧化。 封端剂抑制由氧化暴露或产生的组织中的结合位点的形成，否则在植入时会吸引钙，磷酸盐，免疫原性因子或钙化的其它前体。 在一种方法中，组装的生物假体心脏瓣膜中的组织小叶在脱水和灭菌之前用醛封端剂预处理。
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公开(公告)号：US20140200659A1
公开(公告)日：2014-07-17
申请号：US14139367
申请日：2013-12-23
CPC分类号： A61F2/2415 , A61F2/0095 , A61F2/24 , A61F2/2412 , A61F2/2418 , A61L27/3604 , A61L27/3625 , A61L27/3629 , A61L27/3687 , A61L27/3691 , A61L27/507 , A61L2400/02 , A61L2430/20
摘要： A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification. The method includes applying a calcification mitigant such as a capping agent or an antioxidant to the tissue to specifically inhibit oxidation in tissue. Also, the method can be used to inhibit oxidation in dehydrated tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the oxidation and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde capping agent prior to dehydration and sterilization.
摘要翻译： 用于植入物或组装的生物假体心脏瓣膜中用于减少体内钙化的生物假体组织的治疗。 该方法包括将钙化缓解剂如封端剂或抗氧化剂施用于组织以特异性抑制组织中的氧化。 此外，该方法可用于抑制脱水组织中的氧化。 封端剂抑制由氧化暴露或产生的组织中的结合位点的形成，否则在植入时会吸引钙，磷酸盐，免疫原性因子或钙化的其它前体。 在一种方法中，组装的生物假体心脏瓣膜中的组织小叶在脱水和灭菌之前用醛封端剂预处理。
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23.发明授权公开(公告)号：US12115280B2
公开(公告)日：2024-10-15
申请号：US17127281
申请日：2020-12-18
发明人： Jeffrey S. Dove , Tara J. Tod
CPC分类号： A61L27/3687 , A61L27/50 , A61L27/54 , A61L2430/20 , A61L2430/40
摘要： Methods are provided herein for modifying antigenic carbohydrate epitopes within a xenographic bioprosthetic tissue by oxidation of vicinal diols to form aldehydes or acids and subsequence reductive amination of aldehydes to form stable secondary amines, or amidation or esterification of acids to form stable amides or esters. Advantageously, methods provided herein mitigate the antigenicity of the bioprosthetic tissue while leaving the overall tissue structure substantially undisturbed, and thereby enhance the durability, safety and performance of the bioprosthetic implant.
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公开(公告)号：US20220241462A1
公开(公告)日：2022-08-04
申请号：US17659589
申请日：2022-04-18
摘要： A bioprosthetic tissue having a reduced propensity to calcify in vivo, the bioprosthetic tissue. The bioprosthetic tissue comprises an aldehyde cross-linked and stressed bioprosthetic tissue comprising exposed calcium, phosphate or immunogenic binding sites that have been reacted with a calcification mitigant. The bioprosthetic tissue has a reduced propensity to calcify in vivo as compared to aldehyde cross-linked bioprosthetic tissue that has not been stressed and reacted with the calcification mitigant.
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公开(公告)号：US11305036B2
公开(公告)日：2022-04-19
申请号：US16595089
申请日：2019-10-07
摘要： A bioprosthetic tissue having a reduced propensity to calcify in vivo, the bioprosthetic tissue. The bioprosthetic tissue comprises an aldehyde cross-linked and stressed bioprosthetic tissue comprising exposed calcium, phosphate or immunogenic binding sites that have been reacted with a calcification mitigant. The bioprosthetic tissue has a reduced propensity to calcify in vivo as compared to aldehyde cross-linked bioprosthetic tissue that has not been stressed and reacted with the calcification mitigant.
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公开(公告)号：US10966822B2
公开(公告)日：2021-04-06
申请号：US16253051
申请日：2019-01-21
摘要： A method for manufacturing a heart valve using bioprosthetic tissue that exhibits reduced in vivo calcification. The method includes applying a calcification mitigant such as a capping agent or an antioxidant to the tissue to specifically inhibit oxidation in tissue. Also, the method can be used to inhibit oxidation in dehydrated tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the oxidation and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. In one method, tissue leaflets in assembled bioprosthetic heart valves are pretreated with an aldehyde capping agent prior to dehydration and sterilization.
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公开(公告)号：US10434218B2
公开(公告)日：2019-10-08
申请号：US15879339
申请日：2018-01-24
摘要： A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification is disclosed. The method includes preconditioning, pre-stressing, or pre-damaging fixed bioprosthetic tissue in a manner that mimics the damage associated with post-implant use, while, and/or subsequently applying a calcification mitigant such as a capping agent or a linking agent to the damaged tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the damage process (service stress) and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. The linking agent will act as an elastic reinforcement or shock-absorbing spring element in the tissue structure at the site of damage from the pre-stressing. In one method, tissue leaflets in assembled bioprosthetic heart valves are preconditioned by simulating actual flow conditions for a predetermined number of cycles, during or after which the valve is exposed to the capping agent.
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28.发明授权公开(公告)号：US10238771B2
公开(公告)日：2019-03-26
申请号：US14074379
申请日：2013-11-07
发明人： Dengfeng Xu , Jeffrey S. Dove
IPC分类号： A61L27/36
摘要： Methods for treating a bioprosthetic tissue are described herein. The methods comprise contacting the bioprosthetic tissue with at least one nucleophile and/or at least one electrophile in the presence of a catalytic system comprising at least one or a combination of a fluoride-based salt, a cesium-based salt, a potassium-based salt, a rubidium-based salt, or a carbonate-based salt. The methods may be used to alter functional groups on biological tissue which represent actual and potential calcium binding sites and also processes for cross-linking bioprosthetic tissue. Both processes may be used in conjunction with known fixative techniques, such as glutaraldehyde fixation, or may be used to replace known fixative techniques.
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公开(公告)号：US09168097B2
公开(公告)日：2015-10-27
申请号：US13950154
申请日：2013-07-24
发明人： Jeffrey S. Dove , Bin Tian , Ralph Schneider , Jeffrey S. Cohen , Ivan Jankovic , John F. Migliazza , Gregory A. Wright , James Young , Louis A. Campbell
摘要： Methods for the conditioning of bioprosthetic material employ bovine pericardial membrane. A laser directed at the fibrous surface of the membrane and moved relative thereto reduces the thickness of the membrane to a specific uniform thickness and smoothes the surface. The wavelength, power and pulse rate of the laser are selected which will smooth the fibrous surface as well as ablate the surface to the appropriate thickness. Alternatively, a dermatome is used to remove a layer of material from the fibrous surface of the membrane. Thinning may also employ compression. Stepwise compression with cross-linking to stabilize the membrane is used to avoid damaging the membrane through inelastic compression. Rather, the membrane is bound in the elastic compressed state through addition cross-linking. The foregoing several thinning techniques may be employed together to achieve strong thin membranes.
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30.发明申请METHODS FOR STABILIZING A BIOPROSTHETIC TISSUE BY CHEMICAL MODIFICATION OF ANTIGENIC CARBOHYDRATES 审中-公开通过化学改性抗坏血酸稳定化生物组织的方法公开(公告)号：US20150182665A1
公开(公告)日：2015-07-02
申请号：US14563866
申请日：2014-12-08
发明人： Jeffrey S. Dove
IPC分类号： A61L27/36
CPC分类号： A61L27/3687 , A61L27/50 , A61L27/54 , A61L2430/20 , A61L2430/40
摘要： Methods are provided herein for modifying antigenic carbohydrate epitopes within a xenographic bioprosthetic tissue by oxidation of vicinal diols to form aldehydes or acids and subsequence reductive amination of aldehydes to form stable secondary amines, or amidation or esterification of acids to form stable amides or esters. Advantageously, methods provided herein mitigate the antigenicity of the bioprosthetic tissue while leaving the overall tissue structure substantially undisturbed, and thereby enhance the durability, safety and performance of the bioprosthetic implant.
摘要翻译： 本文提供了用于通过邻位二醇的氧化形成醛或酸并修饰醛的还原胺化以形成稳定的仲胺，或酸的酰胺化或酯化以形成稳定的酰胺或酯，从而改变了生物生物假体组织内的抗原性碳水化合物表位的方法。 有利地，本文提供的方法减轻生物假体组织的抗原性，同时使整个组织结构基本上不受干扰，从而增强生物假体植入物的耐久性，安全性和性能。
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