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1. 发明授权

US07803776B2 Combined use of enzyme inhibitors and of pharmaceutical compositions thereof 失效
标题翻译：酶抑制剂及其药物组合物的组合使用
公开(公告)号：US07803776B2
公开(公告)日：2010-09-28
申请号：US11811565
申请日：2007-06-11
申请人： Siegfried Ansorge , Uwe Lendeckel , Klaus Neubert , Dirk Reinhold , Robert Vetter , Harald Gollnick
发明人： Siegfried Ansorge , Uwe Lendeckel , Klaus Neubert , Dirk Reinhold , Robert Vetter , Harald Gollnick
IPC分类号： A61K31/40 , A61K31/662 , A61K38/05 , A61K38/07
CPC分类号： A61K38/55 , A61K38/05 , A61K38/06 , A61K38/556 , A61K45/06 , A61K2300/00
摘要： Provided are combinations of inhibitors of dipeptidyl peptidase IV (DP IV) and of enzymes having the same substrate specificity (DP IV-analogous enzymatic activity) and inhibitors of alanyl aminopeptidase (aminopeptidase N, APN) and of enzymes having the same substrate specificity (APN-analogous enzymatic activity) and use of the same to obtain a more than additive to superadditive inhibition for the treatment of arteriosclerosis, for the treatment of allergic reactions of the type I according to the Gell and Coombs classification and for the treatment of dermatological diseases with follicular and epidermal hyperkeratoses and an enhanced proliferation of keratinocytes.
摘要翻译：提供二肽基肽酶IV（DP IV）和具有相同底物特异性（DPIV-类似酶活性）的酶和丙氨酰氨肽酶（氨肽酶N，APN）抑制剂和具有相同底物特异性的酶（APN）的酶的组合 - 嗜酸酶活性），并使用它们获得超过添加剂用于治疗动脉硬化的超加性抑制，用于根据凝胶和库姆斯分类治疗I型过敏反应和用于治疗皮肤病学疾病滤泡和表皮角化过度角质形成细胞的增殖。

2. 发明申请

US20090124667A1 Novel Dual-Use Peptidase Inhibitors as Prodrugs for a Therapy of Inflammatory and Other Diseases 失效
公开(公告)号：US20090124667A1
公开(公告)日：2009-05-14
申请号：US12085096
申请日：2006-11-10
申请人： Siegfried Ansorge , Klaus Neubert , Ute Bank , Irene Reichstein , Jurgen Faust , Michael Tager , Petra Fuchs , Bianca Senns
发明人： Siegfried Ansorge , Klaus Neubert , Ute Bank , Irene Reichstein , Jurgen Faust , Michael Tager , Petra Fuchs , Bianca Senns
IPC分类号： A61K31/427 , C07D277/04 , C07D403/12 , C07D417/12 , A61P29/00 , A61K31/4025 , A61P37/00 , A61K31/4439 , A61K31/426
CPC分类号： C07D277/04 , C07D295/185 , C07D417/12 , C07D417/14
摘要： Compounds of the general formulae (1) and (2) A-B-D-B′-A′ (1) and A-B-D-E (2) in which A and A′ may be identical or different and are the residue in which X is S, O, CH2, CH2CH2, CH2O or CH2NH, and Y is H or CN, and * designates a chiral carbon atom preferably in S- or L-configuration; B and B′ may be identical or different and are an O, N or S containing or non-containing, unsubstituted or substituted, unbranched or branched alkylene residue, cycloalkylene residue, aralkylene residue, heterocycloalkylene residue, heteroarylalkylene residue, arylamidoalkylene residue, heteroarylamidoalkylene residue, unsubstituted or mono- or poly-substituted arylene residue or heteroarylene residue having one or more five-, six- or seven-membered ring(s); D is —S—S— or —Se—Se—; and E is the group —CH2—CH(NH2)—R9 or —CH2—*CH(NH2)—R9 respectively in which R9 is an O, N or S containing or non-containing, unsubstituted or substituted, unbranched or branched alkyl residue, cycloalkyl residue, aralkyl residue, heterocycloalkyl residue, heteroarylalkyl residue, arylamidoalkyl residue, heteroarylamidoalkyl residue, unsubstituted or mono- or poly-substituted aryl residue or heteroaryl residue having one or more five-, six- or seven-membered ring(s) and * designates a chiral carbon atom preferably in the S- or L-configuration; or the acid addition salts thereof with organic and/or inorganic acids; as well as to the use of the compounds of the general formulae (1) and (2) in medicine.

3. 发明授权

US07425532B2 Use of alanyl aminopeptidase inhibitors and pharmaceutical compositions containing said inhibitors 失效
标题翻译：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。

4. 发明授权

US08263636B2 Dual alanyl aminopeptidase and dipeptidyl peptidase iv inhibitors for functionally influencing different cells and for treating immunological inflammatory, neuronal and other diseases 失效
标题翻译：双丙氨酰氨基肽酶和二肽基肽酶iv抑制剂功能影响不同细胞和治疗免疫炎症，神经元和其他疾病
公开(公告)号：US08263636B2
公开(公告)日：2012-09-11
申请号：US10575878
申请日：2004-10-15
申请人： Siegfried Ansorge , Ute Bank , Karsten Nordhoff , Michael Taeger , Frank Striggow
发明人： Siegfried Ansorge , Ute Bank , Karsten Nordhoff , Michael Taeger , Frank Striggow
IPC分类号： A61K31/4045 , C07D209/08
CPC分类号： C07C327/48 , C07C233/83 , C07C251/86 , C07D317/60 , C07D401/14 , C07D403/06 , C07D409/14 , C07D413/06 , C07D413/14
摘要： The present invention relates to substances capable of specifically inhibiting Ala-p-nitroanilide-cleaving peptidases and Gly-Pro-p-nitroanilide-cleaving peptidases as well, for a use in the medical field. Furthermore, the invention relates to the use of at least one of such substances or of at least one pharmaceutical or cosmetic composition containing at least one such substance for a prophylaxis or a therapy of diseases, particularly for a prophylaxis and a therapy of diseases accompanied by an excessive immune response (autoimmune diseases, allergies, transplant rejections), of other chronic-inflammatory diseases, of neuronal diseases and cerebral damage, of skin diseases (inter alia acne, psoriasis), of tumor diseases and of specific virus infections (inter alia SARS).
摘要翻译：本发明涉及能够特异性抑制丙氨酸对硝基苯胺切割肽酶和Gly-Pro-对硝基苯胺切割肽酶的物质，用于医疗领域。此外，本发明涉及至少一种这样的物质或至少一种含有至少一种这样的物质的药物或化妆品组合物用于预防或治疗疾病，特别是用于预防和治疗伴随着其他慢性炎性疾病，神经元疾病和脑损伤，皮肤病（尤其是痤疮，牛皮癣），肿瘤疾病和特定病毒感染（特别是其他疾病）的过度免疫应答（自身免疫疾病，过敏，移植排斥） SARS）。

5. 发明授权

US07683034B2 Use of enzyme inhibitors of aminopeptidase N and/or dipeptidylpeptidase IV 失效
标题翻译：使用氨基肽酶N和/或二肽基肽酶IV的酶抑制剂
公开(公告)号：US07683034B2
公开(公告)日：2010-03-23
申请号：US10507548
申请日：2003-03-07
申请人： Siegfried Ansorge , Harald Gollnick , Klaus Neubert , Christos Zouboulis , Jurgen Faust , Uwe Lendeckel , Dirk Reinhold , Robert Vetter
发明人： Siegfried Ansorge , Harald Gollnick , Klaus Neubert , Christos Zouboulis , Jurgen Faust , Uwe Lendeckel , Dirk Reinhold , Robert Vetter
IPC分类号： A61K31/40 , A61K31/662 , A61K38/05 , A61K38/07
CPC分类号： A61K31/195 , A61K38/05 , A61K38/55
摘要： The invention relates to a process for the-inhibition of the DNA synthesis necessary for the proliferation of human sebaceous cells (sebocytes) by the isolated or joint effect of inhibitors of alanyl aminopeptidase (APN) and dipetidyl peptidase IV (DP IV) expressed by these cells. The DNA synthesis (proliferation) of human sebaceous cells is inhibited by the administration of the inhibitors of APN and/or of DP IV depending on the dose. Our invention shows that, for a therapy and for a prevention of dermatological diseases with sebaceous hyperproliferation and modified conditions of differentiation, the application of inhibitors of the above-mentioned enzymes and of corresponding pharmaceutical preparations and dosage forms thereof is suitable.
摘要翻译：本发明涉及通过丙氨酰氨基肽酶（APN）和由这些表达的二肽基肽酶IV（DP IV）的抑制剂的分离或共同作用来抑制人类皮脂细胞（细胞）增殖所必需的DNA合成的方法。细胞。通过根据剂量施用APN和/或DP IV抑制剂来抑制人类皮脂细胞的DNA合成（增殖）。我们的发明表明，对于治疗和预防具有皮脂腺过度增生和改良的分化条件的皮肤病学疾病，上述酶的抑制剂及其相应的药物制剂及其剂型的应用是合适的。

6. 发明申请

US20070212339A1 Use Of At Least One Effector Of Glutathione Metabolism Together With Alpha-Lipoic Acid For The Treatment Of Chronically Obstructive Lung Diseases 审中-公开
标题翻译：使用谷胱甘肽代谢与α-硫辛酸一起治疗长期阻塞性肺疾病
公开(公告)号：US20070212339A1
公开(公告)日：2007-09-13
申请号：US10584072
申请日：2004-12-23
申请人： Siegfried Ansorge , Dieter Koegst , Michael Taeger , Gerhard Fries
发明人： Siegfried Ansorge , Dieter Koegst , Michael Taeger , Gerhard Fries
IPC分类号： A61K38/16 , A61K31/385
CPC分类号： A61K45/06 , A61K31/137 , A61K31/20 , A61K31/366 , A61K2300/00
摘要： The present invention relates to the use of at least one effector of glutathione metabolism together with α-lipoic acid, its salts and/or its pro-drugs for the simultaneous, separate or timed cytoprotective treatment of chronically obstructive lung diseases.
摘要翻译：本发明涉及至少一种谷胱甘肽代谢效应与α-硫辛酸，其盐和/或其前体药物用于长期阻塞性肺疾病的同时，分离或定时细胞保护治疗的用途。

7. 发明申请

US20120258960A1 NOVEL MULTIFUNCTIONAL PEPTIDASE INHIBITORS, ESPECIALLY FOR MEDICAL USE 审中-公开
标题翻译：新型多功能肽抑制剂，特别适用于医疗用途
公开(公告)号：US20120258960A1
公开(公告)日：2012-10-11
申请号：US13393748
申请日：2010-08-26
申请人： Siegfried Ansorge , Ute Bank , Karsten Nordhoff , Peter Roehnert , Sofia Stefin , Frank Striggow , Michael Taeger
发明人： Siegfried Ansorge , Ute Bank , Karsten Nordhoff , Peter Roehnert , Sofia Stefin , Frank Striggow , Michael Taeger
IPC分类号： A61K31/165 , C07D295/192 , A61K31/495 , C07D277/04 , A61K31/426 , C07D243/08 , A61K31/551 , A61K8/42 , A61K8/49 , A61P37/00 , A61P9/10 , A61P25/00 , A61P17/00 , A61P35/00 , A61P37/06 , A61P31/12 , A61P3/10 , C07C237/20
CPC分类号： C07C237/20 , C07C237/22 , C07C271/20 , C07C2601/04 , C07C2601/08 , C07C2601/14 , C07D213/56 , C07D239/26 , C07D263/24 , C07D277/04 , C07D295/192 , C07D333/24
摘要： The invention relates to compounds of the general formula (1) or the acid addition salts thereof with organic and/or inorganic acids; as well as to the use of the compounds of the general formula (1) in medicine.
摘要翻译：本发明涉及通式（1）的化合物或其与有机和/或无机酸的酸加成盐; 以及在药物中使用通式（1）的化合物。

8. 发明申请

US20120028995A1 NOVEL COMPOUNDS FOR MEDICAL USE AS PEPTIDASE EFFECTORS 审中-公开
标题翻译：用于医学用途的新型化合物作为肽类效应物
公开(公告)号：US20120028995A1
公开(公告)日：2012-02-02
申请号：US13185993
申请日：2011-07-19
申请人： Siegfried ANSORGE , Ute BANK , Anke HEIMBURG , Heiko JULIUS , Karsten NORDHOFF , Michael TAEGER
发明人： Siegfried ANSORGE , Ute BANK , Anke HEIMBURG , Heiko JULIUS , Karsten NORDHOFF , Michael TAEGER
IPC分类号： A61K31/52 , C07D209/18 , A61K31/404 , C07C237/20 , A61K31/165 , C07D213/56 , A61K31/4418 , C07D239/26 , A61K31/505 , C07D277/06 , A61K31/426 , C07D271/08 , A61K31/4245 , A61P37/00 , A61P9/10 , A61P25/00 , A61P17/00 , A61P35/00 , A61P37/06 , A61P31/12 , A61P31/04 , A61P1/00 , A61P1/04 , A61P3/10 , A61P29/00 , A61P35/04 , A61P17/06 , A61P17/10 , A61P11/06 , A61P37/08 , A61P11/00 , A61P25/28 , A61P25/16 , A61P25/14 , C12N5/071 , C07D473/00
CPC分类号： C07D473/00 , C07C237/20 , C07C237/22 , C07C237/34 , C07C271/22 , C07C311/47 , C07D209/08 , C07D209/20 , C07D213/55 , C07D213/56 , C07D239/20 , C07D239/26 , C07D271/12 , C07D277/04 , C07D417/12
摘要： The invention relates to compounds of general formula (I) as set forth in the claims as well as to the use of the compounds of the general formula (1) in the medical field, specifically for use in the suppression of DNA synthesis and inflammatory cytokine production as well as in the stimulation of anti-inflammatory cytokine production in vitro and in vivo. This abstract is neither intended to define the invention disclosed in this specification nor intended to limit the scope of the invention in any way.
摘要翻译：本发明涉及权利要求书中阐述的通式（I）化合物以及通式（1）化合物在医学领域中的应用，特别是用于抑制DNA合成和炎性细胞因子生产以及在体外和体内刺激抗炎细胞因子产生。该摘要既不旨在限定本说明书中公开的发明，也不旨在以任何方式限制本发明的范围。

9. 发明授权

US07485626B2 Combinations of enzyme inhibitor-containing preparations and the use thereof 失效
标题翻译：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。

10. 发明授权

US08470855B2 Dual-use peptidase inhibitors as prodrugs for a therapy of inflammatory and other diseases 失效
标题翻译：双用肽酶抑制剂作为治疗炎症和其他疾病的前药
公开(公告)号：US08470855B2
公开(公告)日：2013-06-25
申请号：US12085096
申请日：2006-11-10
申请人： Siegfried Ansorge , Klaus Neubert , Ute Bank , Irene Reichstein , Jürgen Faust , Michael Täger , Petra Fuchs , Bianca Senns
发明人： Siegfried Ansorge , Klaus Neubert , Ute Bank , Irene Reichstein , Jürgen Faust , Michael Täger , Petra Fuchs , Bianca Senns
IPC分类号： A61K31/4439 , A61K31/444 , A61K31/427 , A61K31/4025 , C07D277/04 , C07D207/04 , C07D401/02 , C07D401/14 , C07D417/02 , C07D417/14
CPC分类号： C07D277/04 , C07D295/185 , C07D417/12 , C07D417/14
摘要： Compounds of the general formulae (1) and (2) A-B-D-B′-A′ (1) and A-B-D-E (2) in which A and A′ may be identical or different and are the residue in which X is S, O, CH2, CH2CH2, CH2O or CH2NH, and Y is H or CN, and * designates a chiral carbon atom preferably in S- or L-configuration; B and B′ may be identical or different and are an O, N or S containing or non-containing, unsubstituted or substituted, unbranched or branched alkylene residue, cycloalkylene residue, aralkylene residue, heterocycloalkylene residue, heteroarylalkylene residue, arylamidoalkylene residue, heteroarylamidoalkylene residue, unsubstituted or mono- or poly-substituted arylene residue or heteroarylene residue having one or more five-, six- or seven-membered ring(s); D is —S—S— or —Se—Se—; and E is the group —CH2—CH(NH2)—R9 or —CH2—*CH(NH2)—R9 respectively in which R9 is an O, N or S containing or non-containing, unsubstituted or substituted, unbranched or branched alkyl residue, cycloalkyl residue, aralkyl residue, heterocycloalkyl residue, heteroarylalkyl residue, arylamidoalkyl residue, heteroarylamidoalkyl residue, unsubstituted or mono- or poly-substituted aryl residue or heteroaryl residue having one or more five-, six- or seven-membered ring(s) and * designates a chiral carbon atom preferably in the S- or L-configuration; or the acid addition salts thereof with organic and/or inorganic acids; as well as to the use of the compounds of the general formulae (1) and (2) in medicine.
摘要翻译：通式（1）和（2）ABD-B'-A'（1）和ABDE（2）的化合物，其中A和A'可以相同或不同，并且是其中X是S，O， CH2，CH2CH2，CH2O或CH2NH，Y是H或CN，*表示手性碳原子，优选为S-或L-构型; B和B'可以相同或不同，是含有或不含，未取代或未取代的未支化或支链的亚烷基，亚环烷基，亚芳基残基，杂环亚烷基残基，杂芳基亚烷基残基，芳基酰氨基亚烷基残基，杂芳基酰氨基亚烷基残基未取代的或单取代或多取代的亚芳基或具有一个或多个五元，六元或七元环的杂芳基残基; D是-S-S-或-Se-Se-; 并且E分别是基团-CH 2 -CH（NH 2）-R 9或-CH 2 - * CH（NH 2）-R 9，其中R 9是含有或不含有，未取代或取代的未支化或支链烷基的O，N或S 残基，环烷基残基，芳烷基残基，杂环烷基残基，杂芳基烷基残基，芳基酰氨基烷基残基，杂芳基氨基烷基残基，未取代的或单取代或多取代的芳基残基或具有一个或多个五元，六元或七元环的杂芳基残基，和*表示优选为S-或L-构型的手性碳原子; 或其与有机和/或无机酸的酸加成盐; 以及在药物中使用通式（1）和（2）的化合物。

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