公开(公告)号：US5981621A

公开(公告)日：1999-11-09

申请号：US609921

申请日：1996-02-29

申请人： Jeffrey G. Clark ,  Jeffrey C. Leung

发明人： Jeffrey G. Clark ,  Jeffrey C. Leung

IPC分类号： A61B5/00 ,  A61L24/00 ,  A61L24/06 ,  C08F2/44 ,  C08F20/42 ,  C08J5/12 ,  C09J4/00 ,  C09J7/00 ,  G01J3/18 ,  A61L25/00

CPC分类号： A61L24/06 ,  A61B5/14532 ,  A61B5/1455 ,  A61L24/0021 ,  C09J4/00 ,  G01J3/1804

摘要： A biocompatible monomer composition includes: (A) at least one monomer, which forms a medically acceptable polymer; (B) at least one plasticizing agent present in the composition in an amount of from 0.5 wt. % to 15 wt. % of the composition; and (C) at least one acidic stabilizing agent having a pK.sub.a ionization constant of from about 1 to about 7. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g., body tissues, includes (a) holding damaged tissue edges together to form abutted tissue surfaces; (b) applying to the abutted tissue surfaces an excessive amount of a composition containing 1) at least one monomer, which forms a medically acceptable biodegradable polymer, 2) at least one plasticizing agent; and 3) at least one acidic stabilizing agent; and (c) maintaining the surfaces in contact until the composition polymerizes to form a thick film of polymerized composition bridging the abutted tissue surfaces.

公开(公告)号：US5624669A

公开(公告)日：1997-04-29

申请号：US483969

申请日：1995-06-07

申请人： Jeffrey C. Leung ,  Jeffrey G. Clark

发明人： Jeffrey C. Leung ,  Jeffrey G. Clark

IPC分类号： A61L24/06 ,  C09J4/00 ,  A61K31/74 ,  A61F2/02 ,  A61K9/14 ,  A61K9/48

CPC分类号： A61L24/06 ,  C09J4/00 ,  A61L2400/04 ,  Y10S514/963

摘要： Hemostatic procedures for sealing punctures and incisions in blood vessels and internal organs involve applying to a puncture or incision surface a biocompatible adhesive composition.

摘要翻译： 用于密封血管和内脏中的穿刺和切口的止血程序包括向穿刺或切口表面施加生物相容性粘合剂组合物。

公开(公告)号：US5582834A

公开(公告)日：1996-12-10

申请号：US461408

申请日：1995-06-05

申请人： Jeffrey C. Leung ,  Jeffrey G. Clark

发明人： Jeffrey C. Leung ,  Jeffrey G. Clark

IPC分类号： A61L24/00 ,  A61L24/06 ,  C09J4/00 ,  A61F2/28 ,  A61K9/14 ,  A61K31/785 ,  A61K31/795

CPC分类号： A61L24/06 ,  C09J4/00 ,  Y10S514/963

摘要： A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g., body tissues, includes (a) applying to at least one of the surfaces a composition containing 1) at least one monomer, preferably an alpha-cyanoacrylate, which forms a polymer whose in vivo biodegradation produces formaldehyde; and 2) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger; and (b) maintaining the surfaces in contact until the composition polymerizes.

摘要翻译： 生物相容性单体组合物含有（A）至少一种下式的单体：CHR = CXY其中X和Y各自为强吸电子基团，R为H，或者X和Y均为氰基，C1-C4 烷基; 和（B）有效量的至少一种有效降低活性甲醛浓度水平的生物相容剂，优选甲醛清除剂化合物。 单体优选为α-氰基丙烯酸酯。 甲醛清除剂化合物可以是微囊化或非微囊化形式。 组合物可以应用于各种材料，并且特别适合作为体内组织粘合剂。 在体内将两个表面（例如身体组织）接合在一起的方法包括（a）向至少一个表面施用包含1）至少一种形成其体内聚合物的单体，优选α-氰基丙烯酸酯的组合物 生物降解产生甲醛; 和2）有效量的至少一种有效降低活性甲醛浓度水平的生物相容剂，优选甲醛清除剂; 和（b）保持表面接触直到组合物聚合。

公开(公告)号：US6143352A

公开(公告)日：2000-11-07

申请号：US714288

申请日：1996-09-18

申请人： Jeffrey G. Clark ,  Jeffrey C. Leung

发明人： Jeffrey G. Clark ,  Jeffrey C. Leung

IPC分类号： A61K47/30 ,  A61L24/00 ,  A61L24/04 ,  A61L24/06 ,  A61L27/00 ,  A61L27/16 ,  A61L27/26 ,  C08F2/00 ,  C09J4/00 ,  C09J4/04 ,  B05D3/00

CPC分类号： A61L27/26 ,  A61L24/043 ,  A61L24/06 ,  A61L27/16 ,  C09J4/00

摘要： The pH-modified monomer and polymer compositions are useful as biomedical and surgical adhesives, sealants, implants and bioactive agent release carriers or matrices. They comprise a monomer or polymer; and an effective amount of an acidic or basic pH modifier effective to modify the pH of an immediate in vivo environment of the composition to a pH range at which the polymer biodegrades at a different rate than at physiologic pH. The invention also relates to in vivo applications in which surfaces are joined or treated with such pH-modified biocompatible compositions.

摘要翻译： pH改性的单体和聚合物组合物可用作生物医学和外科粘合剂，密封剂，植入物和生物活性剂释放载体或基质。 它们包含单体或聚合物; 和有效量的酸性或碱性pH调节剂有效地将组合物的即时体内环境的pH改变到聚合物以与生理pH不同的速率生物降解的pH范围。 本发明还涉及其中表面用这种pH-改性的生物相容性组合物连接或处理的体内应用。

公开(公告)号：US6010714A

公开(公告)日：2000-01-04

申请号：US755007

申请日：1996-11-22

申请人： Jeffrey C. Leung ,  Jeffrey G. Clark

发明人： Jeffrey C. Leung ,  Jeffrey G. Clark

IPC分类号： A61L24/00 ,  A61F13/02

CPC分类号： A61L24/001

摘要： A biocompatible monomer composition includes at least one monomer, which forms a medically acceptable polymer, and an effective amount of at least one heat dissipating agent sufficient to reduce exothermic polymerization temperature increase of the composition. The heat dissipating agent enhances patient comfort and prevents necrosis of living tissue normally encountered with such medical adhesives.

摘要翻译： 生物相容性单体组合物包括形成医学上可接受的聚合物的至少一种单体和足以降低组合物的放热聚合温度升高的有效量的至少一种散热剂。 散热剂增强了患者的舒适度并防止了这种医用粘合剂通常遇到的生物体组织的坏死。

公开(公告)号：US5514371A

公开(公告)日：1996-05-07

申请号：US215584

申请日：1994-03-22

申请人： Jeffrey C. Leung ,  Jeffrey G. Clark

发明人： Jeffrey C. Leung ,  Jeffrey G. Clark

IPC分类号： A61L24/00 ,  A61L24/06 ,  C09J4/00 ,  A61K31/785 ,  A61K9/14 ,  A61K31/795 ,  B01J13/02

CPC分类号： A61L24/06 ,  C09J4/00 ,  Y10S514/963

摘要： A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g., body tissues, includes (a) applying to at least one of the surfaces a composition containing 1) at least one monomer, preferably an alpha-cyanoacrylate, which forms a polymer whose in vivo biodegradation produces formaldehyde; and 2) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger; and (b) maintaining the surfaces in contact until the composition polymerizes.

摘要翻译： 生物相容性单体组合物含有（A）至少一种下式的单体：CHR = CXY其中X和Y各自为强吸电子基团，R为H，或者X和Y均为氰基，C1-C4 烷基; 和（B）有效量的至少一种有效降低活性甲醛浓度水平的生物相容剂，优选甲醛清除剂化合物。 单体优选为α-氰基丙烯酸酯。 甲醛清除剂化合物可以是微囊化或非微囊化形式。 组合物可以应用于各种材料，并且特别适合作为体内组织粘合剂。 在体内将两个表面（例如身体组织）接合在一起的方法包括（a）向至少一个表面施用包含1）至少一种形成其体内聚合物的单体，优选α-氰基丙烯酸酯的组合物 生物降解产生甲醛; 和2）有效量的至少一种有效降低活性甲醛浓度水平的生物相容剂，优选甲醛清除剂; 和（b）保持表面接触直到组合物聚合。

公开(公告)号：US5328687A

公开(公告)日：1994-07-12

申请号：US040618

申请日：1993-03-31

申请人： Jeffrey C. Leung ,  Jeffrey G. Clark

发明人： Jeffrey C. Leung ,  Jeffrey G. Clark

IPC分类号： A61L24/00 ,  A61L24/06 ,  C09J4/00 ,  A61K31/74 ,  A61K9/14 ,  C08F120/44 ,  C08F222/34

CPC分类号： A61L24/06 ,  C09J4/00 ,  Y10S514/963

摘要： A biocompatible monomer composition contains (A) at least one monomer of the formula:CHR.dbd.CXYwherein X and Y are each strong electron withdrawing groups, and R is H or, provided that X and Y are both cyano groups, a C.sub.1 -C.sub.4 alkyl group; and (B) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger compound. The monomer is preferably an alpha-cyanoacrylate. The formaldehyde scavenger compound may be in microencapsulated or non-microencapsulated form. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g., body tissues, includes (a) applying to at least one of the surfaces a composition containing 1) at least one monomer, preferably an alpha-cyanoacrylate, which forms a polymer whose in vivo biodegradation produces formaldehyde; and 2) an effective amount of at least one biocompatible agent effective to reduce active formaldehyde concentration levels, preferably a formaldehyde scavenger; and (b) maintaining the surfaces in contact until the composition polymerizes.

摘要翻译： 生物相容性单体组合物含有（A）至少一种下式的单体：CHR = CXY其中X和Y各自为强吸电子基团，R为H，或者X和Y均为氰基，C1-C4 烷基; 和（B）有效量的至少一种有效降低活性甲醛浓度水平的生物相容剂，优选甲醛清除剂化合物。 单体优选为α-氰基丙烯酸酯。 甲醛清除剂化合物可以是微囊化或非微囊化形式。 组合物可以应用于各种材料，并且特别适合作为体内组织粘合剂。 在体内将两个表面（例如身体组织）接合在一起的方法包括（a）向至少一个表面施用包含1）至少一种形成其体内聚合物的单体，优选α-氰基丙烯酸酯的组合物 生物降解产生甲醛; 和2）有效量的至少一种有效降低活性甲醛浓度水平的生物相容剂，优选甲醛清除剂; 和（b）保持表面接触直到组合物聚合。

公开(公告)号：US06565840B1

公开(公告)日：2003-05-20

申请号：US08909845

申请日：1997-08-12

申请人： Jeffrey G. Clark ,  Jeffrey C. Leung

发明人： Jeffrey G. Clark ,  Jeffrey C. Leung

IPC分类号： A61L2500

CPC分类号： A61L24/06 ,  A61B5/14532 ,  A61B5/1455 ,  A61L24/0021 ,  C09J4/00 ,  G01J3/1804 ,  C08L35/04 ,  C08F222/32

摘要： A biocompatible monomer composition includes: (A) at least one monomer, which forms a medically acceptable polymer; (B) at least one plasticizing agent present in the composition in an amount of from 0.5 wt. % to 15 wt. % of the composition; and (C) at least one acidic stabilizing agent having a pKa ionization constant of from about 1 to about 7. The composition can be applied to a variety of materials and is particularly suitable as in vivo tissue adhesive. A method of joining together in vivo two surfaces, e.g., body tissues, includes (a) holding damaged tissue edges together to form abutted tissue surfaces; (b) applying to the abutted tissue surfaces an excessive amount of a composition containing 1) at least one monomer, which forms a medically acceptable biodegradable polymer, 2) at least one plasticizing agent; and 3) at least one acidic stabilizing agent; and (c) maintaining the surfaces in contact until the composition polymerizes to form a thick film of polymerized composition bridging the abutted tissue surfaces.

摘要翻译： 生物相容性单体组合物包括：（A）至少一种形成医学上可接受的聚合物的单体; （B）组合物中存在的至少一种增塑剂的量为0.5wt。 ％至15wt。 ％的组成; 和（C）至少一种具有约1至约7的pKa电离常数的酸性稳定剂。该组合物可以应用于各种材料，并且特别适合作为体内组织粘合剂。 在体内将两个表面（例如身体组织）接合在一起的方法包括（a）将损伤的组织边缘保持在一起以形成邻接的组织表面; （b）向邻接的组织表面施加过量的组合物，其含有1）至少一种形成医学上可接受的生物可降解聚合物的单体，2）至少一种增塑剂; 和3）至少一种酸性稳定剂; 和（c）保持表面接触直到组合物聚合以形成桥接邻接组织表面的聚合组合物的厚膜。

公开(公告)号：US06306243B1

公开(公告)日：2001-10-23

申请号：US09588621

申请日：2000-06-07

申请人： Jeffrey G. Clark ,  Jeffrey C. Leung

发明人： Jeffrey G. Clark ,  Jeffrey C. Leung

IPC分类号： C09J10100

CPC分类号： A61L27/26 ,  A61L24/043 ,  A61L24/06 ,  A61L27/16 ,  C09J4/00 ,  C08L35/04 ,  C08F222/00

摘要： The pH-modified monomer and polymer compositions are useful as biomedical and surgical adhesives, sealants, implants and bioactive agent release carriers or matrices. They comprise a monomer or polymer; and an effective amount of an acidic or basic pH modifier effective to modify the pH of an immediate in vivo environment of the composition to a pH range at which the polymer biodegrades at a different rate than at physiologic pH. The invention also relates to in vivo applications in which surfaces are joined or treated with such pH-modified biocompatible compositions.

摘要翻译： pH改性的单体和聚合物组合物可用作生物医学和外科粘合剂，密封剂，植入物和生物活性剂释放载体或基质。 它们包含单体或聚合物; 和有效量的酸性或碱性pH调节剂有效地将组合物的即时体内环境的pH改变到聚合物以与生理pH不同的速率生物降解的pH范围。 本发明还涉及其中表面用这种pH-改性的生物相容性组合物连接或处理的体内应用。

公开(公告)号：US06217603B1

公开(公告)日：2001-04-17

申请号：US08920876

申请日：1997-08-29

申请人： Jeffrey G. Clark ,  Jeffrey C. Leung

发明人： Jeffrey G. Clark ,  Jeffrey C. Leung

IPC分类号： A61B1708

CPC分类号： A61L24/0021 ,  A61L24/06 ,  Y10S514/963 ,  Y10T428/3192 ,  C08L35/04

摘要： A method of joining together in vivo living tissue surfaces includes (a) holding together at least two tissue surfaces to form abutted tissue surfaces, (b) applying across the abutted tissue surfaces an excessive amount of an adhesive composition comprising at least one monomer that forms a medically acceptable polymer with an applicator having a porous applicator tip; and (c) maintaining the tissue surfaces in contact in vivo until the composition polymerizes to form a thick film of polymerized composition on the abutted tissue surface.

摘要翻译： 将体内生物组织表面接合在一起的方法包括（a）将至少两个组织表面保持在一起以形成邻接的组织表面，（b）跨过邻接的组织表面施加过量的包含至少一种形成的单体的粘合剂组合物 具有涂敷器的医学上可接受的聚合物，其具有多孔施用器尖端; 和（c）保持组织表面在体内接触直到组合物聚合以在邻接的组织表面上形成聚合组合物的厚膜。