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1. 发明申请

WO2011119754A2 METHODS OF CONDITIONING SHEET BIOPROSTHETIC TISSUE 审中-公开
标题翻译：调节片生物组织的方法
公开(公告)号：WO2011119754A2
公开(公告)日：2011-09-29
申请号：PCT/US2011/029654
申请日：2011-03-23
申请人： EDWARDS LIFESCIENCES CORPORATION , DOVE, Jeffrey, S. , TIAN, Bin , SCHNEIDER, Ralph , COHEN, Jeffrey, S. , JANKOVIC, Ivan , MIGLIAZZA, John, F. , WRIGHT, Gregory, A. , YOUNG, James, M. , CAMPBELL, Louis, A.
发明人： DOVE, Jeffrey, S. , TIAN, Bin , SCHNEIDER, Ralph , COHEN, Jeffrey, S. , JANKOVIC, Ivan , MIGLIAZZA, John, F. , WRIGHT, Gregory, A. , YOUNG, James, M. , CAMPBELL, Louis, A.
IPC分类号： A61F2/24 , A61L27/38 , D06M10/00 , D06M10/04
CPC分类号： A61F2/2415 , A61B18/20 , A61F2/02 , A61F2/24 , A61F2/2409 , A61F2/2418 , A61F2002/30324 , A61F2250/0036 , A61L27/3604 , A61L27/3625 , A61L27/3691 , A61L27/507 , A61L2300/60 , A61L2430/20 , B65B55/18 , B65B63/02
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. The finally thinned membrane may then be treated by capping of calcification nucleation sites and borohydride reduction. The leaflets may be formed to have more than one region of uniform thickness, such as a thicker peripheral sewing region.
摘要翻译：生物假体材料调理方法采用牛心包膜。指向膜的纤维表面并相对于其移动的激光将膜的厚度减小到特定的均匀厚度并平滑表面。选择激光器的波长，功率和脉冲速率，这将使纤维表面平滑，并将表面烧蚀到合适的厚度。或者，使用皮肤表面从膜的纤维表面去除一层材料。变薄也可能采用压缩。使用交联以稳定膜的逐步压缩来避免通过非弹性压缩损伤膜。相反，膜通过加成交联结合在弹性压缩状态。上述几种稀释技术可以一起使用以获得强的薄膜。然后可以通过封闭钙化成核位点和硼氢化钠还原来处理最终变薄的膜。传单可以形成为具有多于一个均匀厚度的区域，例如较厚的外围缝合区域。

2. 发明申请

WO2015047771A1 METHOD AND APPARATUS FOR PREPARING A CONTOURED BIOLOGICAL TISSUE 审中-公开
标题翻译：用于制备组织生物组织的方法和装置
公开(公告)号：WO2015047771A1
公开(公告)日：2015-04-02
申请号：PCT/US2014/055647
申请日：2014-09-15
申请人： EDWARDS LIFESCIENCES CORPORATION
发明人： MUNNELLY, Amy, E. , DOVE, Jeffrey, S. , LEE, Minsey
IPC分类号： C12M1/42 , C12M3/00 , A61F2/00
CPC分类号： A61F2/2415 , A61F2/2412 , A61F2240/004
摘要： An assembly and methods for providing a contoured biological tissue are described. The assembly comprises a first plate and a second plate. The first plate is configured to receive a biological tissue. The second plate is configured to apply a compressive force on the biological tissue that is disposed on the first plate. One or both of the first and second plates comprise a defined shape and a contoured area within the defined shape. The contoured area comprises at least first and second elevations and a continuous transition between the first and second transitions. One or more energy sources is associated with one or both of the first and second plates. The one or more energy sources delivers energy while the second plate applies the compressive force on the biological tissue disposed on the first plate.
摘要翻译：描述了用于提供轮廓生物组织的组件和方法。组件包括第一板和第二板。第一板被配置成接收生物组织。第二板构造成对设置在第一板上的生物组织施加压缩力。第一和第二板中的一个或两个包括限定形状和限定形状内的轮廓区域。轮廓区域包括至少第一和第二高程以及第一和第二过渡之间的连续过渡。一个或多个能源与第一和第二板中的一个或两个相关联。一个或多个能量源传递能量，而第二板将压缩力施加在设置在第一板上的生物组织上。

3. 发明申请

WO2014074870A1 METHODS FOR TREATING BIOPROSTHETIC TISSUE USING A NUCLEOPHILE/ELECTROPHILE IN A CATALYTIC SYSTEM 审中-公开
标题翻译：在催化体系中使用核仁/电极处理生物组织的方法
公开(公告)号：WO2014074870A1
公开(公告)日：2014-05-15
申请号：PCT/US2013/069230
申请日：2013-11-08
申请人： EDWARDS LIFESCIENCES CORPORATION
发明人： XU, Dengfeng , DOVE, Jeffrey, S.
IPC分类号： A61L27/56 , A61L27/38 , C12N5/07
CPC分类号： A61L27/3687 , A61L2400/02 , A61L2430/40
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.
摘要翻译：本文描述了治疗生物假体组织的方法。所述方法包括在催化体系存在下使生物假纤维组织与至少一种亲核试剂和/或至少一种亲电试剂接触，所述催化体系包含氟化物基盐，铯基盐，基于钾的盐盐，铷基盐或碳酸盐基盐。这些方法可用于改变代表实际和潜在的钙结合位点的生物组织上的官能团以及交联生物假体组织的方法。两种方法可以与已知的固定技术结合使用，例如戊二醛固定，或可用于替代已知的固定技术。

4. 发明申请

WO2011160085A3 METHODS FOR STABILIZING A BIOPROSTHETICS TISSUE BY CHEMICAL MODIFICATION OF ANTIGENIC CARBOHYDRATES 审中-公开
公开(公告)号：WO2011160085A3
公开(公告)日：2011-12-22
申请号：PCT/US2011/040984
申请日：2011-06-17
申请人： EDWARDS LIFESCIENCES CORPORATION , DOVE, Jeffrey, S. , TOD, Tara
发明人： DOVE, Jeffrey, S. , TOD, Tara
IPC分类号： A61L27/50 , A61L27/54 , A61L2/16 , A61F2/02
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 animation 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.

5. 发明申请

WO2009085199A2 CAPPING BIOPROSTHETIC TISSUE TO REDUCE CALCIFICATION 审中-公开
标题翻译：采用生物瓣组织来减少钙化
公开(公告)号：WO2009085199A2
公开(公告)日：2009-07-09
申请号：PCT/US2008/013879
申请日：2008-12-19
申请人： EDWARDS LIFESCIENCES CORPORATION , DOVE, Jeffrey, S. , DOBLER, Darin , DAVIDSON, Jim, A.
发明人： DOVE, Jeffrey, S. , DOBLER, Darin , DAVIDSON, Jim, A.
IPC分类号： A61L27/54 , A61L27/36
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：一种用于植入物或组装的生物假体心脏瓣膜以减少体内钙化的生物假体组织的治疗。该方法包括向组织中施加钙化缓解剂如封闭剂或抗氧化剂以特异性地抑制组织中的氧化。而且，该方法可以用于抑制脱水组织中的氧化。封闭剂抑制组织中由氧化所暴露或产生的结合位点的形成，否则将在植入时吸引钙，磷酸盐，免疫原性因子或其他钙化前体。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。

6. 发明申请

WO2006104820A2 TREATMENT OF BIOPROSTHETIC TISSUES TO MITIGATE POST IMPLANTATION CALCIFICATION 审中-公开
标题翻译：生物多样性组织的治疗以减少后期植入计算
公开(公告)号：WO2006104820A2
公开(公告)日：2006-10-05
申请号：PCT/US2006/010540
申请日：2006-03-24
申请人： EDWARDS LIFESCIENCES CORPORATION , DOVE, Jeffrey, S.
发明人： DOVE, Jeffrey, S.
IPC分类号： A61L27/36
CPC分类号： A61L27/3683 , A61L27/3604 , A61L2400/02
摘要： The present invention provides methods for treating tissue to inhibit post-implant calcification of a biological tissue. In one method of this invention, a tissue is immersed in or otherwise contacted with a pretreated glutaraldehyde solution, i.e., a heat-treated or pH-adjusted glutaraldehyde solution. The tissue may be partially fixed with glutaraldehyde prior to, after, or concurrently with the step of contacting the tissue with the pretreated gluteraldehyde. Contact with the pretreated gluteraldehyde produces free amine groups on the tissue, which are subsequently blocked by contacting the crosslinked tissue with a blocking agent. In another embodiment, a tissue is contacted with either a non- pretreated glutaraldehyde or a pH-adjusted glutaraldehyde solution for a period of time sufficient to crosslink the tissue. The crosslinked tissue is then treated with a reducing agent that reduces aldehyde and carboxylic acid groups on the fixed tissue.
摘要翻译：本发明提供了治疗组织以抑制生物组织的植入后钙化的方法。在本发明的一种方法中，将组织浸入或以其它方式与预处理的戊二醛溶液即热处理或pH调节的戊二醛溶液接触。在使组织与预处理的戊二醛接触的步骤之前，之后或同时，组织可以用戊二醛部分固定。与预处理的戊二醛接触在组织上产生游离胺基，随后通过使交联的组织与封闭剂接触来阻断。在另一个实施方案中，将组织与未预处理的戊二醛或pH调节的戊二醛溶液接触足够交联组织的时间。然后用还原剂处理交联的组织，还原剂可以减少固定组织上的醛和羧酸基团。

7. 发明授权

EP2582411B1 METHODS FOR STABILIZING A BIOPROSTHETIC TISSUE BY CHEMICAL MODIFICATION OF ANTIGENIC CARBOHYDRATES 有权
公开(公告)号：EP2582411B1
公开(公告)日：2019-05-01
申请号：EP11796556.6
申请日：2011-06-17
申请人： Edwards Lifesciences Corporation
发明人： DOVE, Jeffrey, S. , TOD, Tara
IPC分类号： A61L27/50 , A61L27/54 , A61L2/16 , A61F2/02 , A61L27/36

8. 发明公开

EP2234657A2 CAPPING BIOPROSTHETIC TISSUE TO REDUCE CALCIFICATION 有权
标题翻译： COVER生物人工组织用于减少钙化
公开(公告)号：EP2234657A2
公开(公告)日：2010-10-06
申请号：EP08866741.5
申请日：2008-12-19
申请人： Edwards Lifesciences Corporation
发明人： DOVE, Jeffrey, S. , DOBLER, Darin , DAVIDSON, Jim, A. , WRIGHT,Gregory,A.
IPC分类号： A61L27/54 , A61L27/36
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.

9. 发明授权

EP2916882B1 METHODS FOR TREATING BIOPROSTHETIC TISSUE USING A NUCLEOPHILE/ELECTROPHILE IN A CATALYTIC SYSTEM 有权
公开(公告)号：EP2916882B1
公开(公告)日：2020-07-15
申请号：EP13853003.5
申请日：2013-11-08
申请人： Edwards Lifesciences Corporation
发明人： XU, Dengfeng , DOVE, Jeffrey, S.
IPC分类号： A61L27/56 , A61L27/38 , C12N5/07

10. 发明公开

EP2916882A1 METHODS FOR TREATING BIOPROSTHETIC TISSUE USING A NUCLEOPHILE/ELECTROPHILE IN A CATALYTIC SYSTEM 有权
标题翻译：法处理生物假体组织使用亲核/电在催化体系
公开(公告)号：EP2916882A1
公开(公告)日：2015-09-16
申请号：EP13853003.5
申请日：2013-11-08
申请人： Edwards Lifesciences Corporation
发明人： XU, Dengfeng , DOVE, Jeffrey, S.
IPC分类号： A61L27/56 , A61L27/38 , C12N5/07
CPC分类号： A61L27/3687 , A61L2400/02 , A61L2430/40
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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