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    Combinations of enzyme inhibitor-containing preparations and the use thereof
    1.
    发明授权
    Combinations of enzyme inhibitor-containing preparations and the use thereof 失效
    含酶抑制剂制剂的组合及其用途

    公开(公告)号：US07485626B2

    公开(公告)日：2009-02-03

    申请号：US10296102

    申请日：2001-05-22

    申请人： Siegfried Ansorge ,  Marco Arndt ,  Frank Buehling ,  Uwe Lendeckel ,  Klaus Neubert ,  Dirk Reinhold ,  Stefan Brocke

    发明人： Siegfried Ansorge ,  Marco Arndt ,  Frank Buehling ,  Uwe Lendeckel ,  Klaus Neubert ,  Dirk Reinhold ,  Stefan Brocke

    IPC分类号： A61K38/00 ,  A61K31/69 ,  A61K31/675 ,  A61K31/445 ,  A01N55/08 ,  A01N43/40 ,  A01N43/36

    CPC分类号： A61K45/06 ,  A61K38/55 ,  A61K2300/00

    摘要： The invention comprises a process wherein the DNA synthesis and, thus, the proliferation of mononuclear cells (MNZ) and of T cells as well is inhibited by the simultaneous and combined inhibition of the enzyme activity (I) of alanyl aminopeptidase and of dipeptidyl peptidase IV; (II) of dipeptidyl peptidase IV and of the angiotensin-converting enzyme; (III) of dipeptidyl peptidase IV and of prolyl oligopeptidase; and (IV) of dipeptidyl peptidase IV and of X-Pro-aminopeptidase to an extent which cannot be achieved by an application of a single one of said enzyme inhibitors, even at a higher dosage. Although the said inhibitors exercise an influence on the very same process finally, i.e. the DNA synthesis and, thus, the proliferation of immune cells, this effect is not complete and is not long lasting when a single inhibitor is applied. From the functional overlap of enzymatic activities results an additive/superadditive inhibitory effect on the DNA synthesis and proliferation by the simultaneous inhibition of more than one of the above enzymes, as our data show.Our invention shows that the simultaneous application of substances inhibiting the above enzymes or of corresponding preparations and administration forms, respectively, is well suitable for a therapy of autoimmune diseases and chronic diseases with an inflammatory genesis as well as for a treatment of rejection episodes after a transplantation.

    摘要翻译： 本发明包括其中DNA合成以及单核细胞（MNZ）和T细胞增殖以及通过丙氨酰氨基肽酶和二肽基肽酶IV的酶活性（I）的同时和组合的抑制而被抑制的方法 ; （II）二肽基肽酶IV和血管紧张素转换酶; （III）二肽基肽酶IV和脯氨酰寡肽酶; 和（IV）二肽基肽酶IV和X-Pro-氨基肽酶的程度，即使在较高剂量下也不能通过施用单一的所述酶抑制剂来实现。 虽然所述抑制剂最终对相同的方法（即DNA合成，因此也是免疫细胞的增殖）产生影响，但是这种作用不完全，并且当单一抑制剂被应用时不会持久。 从我们的数据显示，酶活性的功能重叠通过同时抑制上述一种以上的酶，导致对DNA合成和增殖的添加/超加成抑制作用。 我们的发明表明，分别同时施用抑制上述酶或相应的制剂和给药形式的物质，非常适合用于治疗自身免疫性疾病和具有炎性发生的慢性疾病以及治疗后的排斥发作 移植。

    Combinations of enzyme inhibitor-containing preparations and the use thereof
    2.
    发明申请
    Combinations of enzyme inhibitor-containing preparations and the use thereof 失效
    含酶抑制剂制剂的组合及其用途

    公开(公告)号：US20050014699A1

    公开(公告)日：2005-01-20

    申请号：US10296102

    申请日：2001-05-22

    申请人： Siegfried Ansorge ,  Marco Arndt ,  Frank Buehling ,  Uwe Lendeckel ,  Klaus Neubert ,  Dirk Reinhold ,  Stefan Brocke

    发明人： Siegfried Ansorge ,  Marco Arndt ,  Frank Buehling ,  Uwe Lendeckel ,  Klaus Neubert ,  Dirk Reinhold ,  Stefan Brocke

    IPC分类号： A61K31/40 ,  A61K31/401 ,  A61K31/4164 ,  A61K31/425 ,  A61K31/445 ,  A61K31/4453 ,  A61K38/55 ,  A61K45/06 ,  A61P1/04 ,  A61P3/10 ,  A61P7/06 ,  A61P9/00 ,  A61P9/10 ,  A61P13/12 ,  A61P17/00 ,  A61P25/28 ,  A61P35/00 ,  A61P37/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  A61K38/04 ,  A61K31/675 ,  A61K31/69

    CPC分类号： A61K45/06 ,  A61K38/55 ,  A61K2300/00

    摘要： The invention comprises a process wherein the DNA synthesis and, thus, the proliferation of mononuclear cells (MNZ) and of T cells as well is inhibited by the simultaneous and combined inhibition of the enzyme activity (I) of alanyl aminopeptidase and of dipeptidyl peptidase IV; (II) of dipeptidyl peptidase IV and of the angiotensin-converting enzyme; (III) of dipeptidyl peptidase IV and of prolyl oligopeptidase; and (IV) of dipeptidyl peptidase IV and of X-Pro-aminopeptidase to an extent which cannot be achieved by an application of a single one of said enzyme inhibitors, even at a higher dosage. Although the said inhibitors exercise an influence on the very same process finally, i.e. the DNA synthesis and, thus, the proliferation of immune cells, this effect is not complete and is not long lasting when a single inhibitor is applied. From the functional overlap of enzymatic activities results an additive/superadditive inhibitory effect on the DNA synthesis and proliferation by the simultaneous inhibition of more than one of the above enzymes, as our data show. Our invention shows that the simultaneous application of substances inhibiting the above enzymes or of corresponding preparations and administration forms, respectively, is well suitable for a therapy of autoimmune diseases and chronic diseases with an inflammatory genesis as well as for a treatment of rejection episodes after a transplantation.

    摘要翻译： 本发明包括其中DNA合成以及单核细胞（MNZ）和T细胞增殖以及通过丙氨酰氨基肽酶和二肽基肽酶IV的酶活性（I）的同时和组合的抑制而被抑制的方法 ; （II）二肽基肽酶IV和血管紧张素转换酶; （III）二肽基肽酶IV和脯氨酰寡肽酶; 和（IV）二肽基肽酶IV和X-Pro-氨基肽酶的程度，即使在较高剂量下也不能通过施用单一的所述酶抑制剂来实现。 虽然所述抑制剂最终对相同的方法（即DNA合成，因此也是免疫细胞的增殖）产生影响，但是这种作用不完全，并且当单一抑制剂被应用时不会持久。 从我们的数据显示，酶活性的功能重叠通过同时抑制上述一种以上的酶，导致对DNA合成和增殖的添加/超加成抑制作用。 我们的发明表明，分别同时施用抑制上述酶或相应的制剂和给药形式的物质，非常适合用于治疗自身免疫性疾病和具有炎性发生的慢性疾病以及治疗后的排斥发作 移植。

    Use of alanyl aminopeptidase inhibitors and pharmaceutical compositions containing said inhibitors
    9.
    发明授权
    Use of alanyl aminopeptidase inhibitors and pharmaceutical compositions containing said inhibitors 失效
    丙氨酰氨基肽酶抑制剂和含有所述抑制剂的药物组合物的用途

    公开(公告)号：US07425532B2

    公开(公告)日：2008-09-16

    申请号：US10520014

    申请日：2003-07-04

    申请人： Siegfried Ansorge ,  Janine Tadje ,  Uwe Lendeckel

    发明人： Siegfried Ansorge ,  Janine Tadje ,  Uwe Lendeckel

    IPC分类号： A61K38/05 ,  A61K31/495

    CPC分类号： A61K31/66 ,  A61K38/1709 ,  A61K2300/00

    摘要： The present invention relates to the use of one inhibitor or of several inhibitors of alanyl aminopeptidases and/or of enzymes having a similar substrate specificity for the induction of the production of TGF-β1 and of the expression of TGF-β1 in and/or on Treg cells and relates to the use for preventing and/or treating autoimmune diseases, allergies, arteriosclerosis and for suppressing graft rejection reactions. The invention furthermore relates to uses, wherein peptide fragments of pathogenic autoantigens or synthetic analogs and/or specific antigenic components of pathogenic microorganisms are used in addition.

    摘要翻译： 本发明涉及一种抑制剂或几种丙氨酸氨基肽酶抑制剂和/或具有相似底物特异性的酶诱导TGF-β1的产生和TGF-β1在和/或其中的表达的用途的用途 Treg细胞，涉及预防和/或治疗自身免疫性疾病，过敏，动脉硬化和抑制移植排斥反应的用途。 本发明还涉及另外使用病原性自身抗原的肽片段或病原​​微生物的合成类似物和/或特异抗原成分的用途。