Imtm Gmbh

Keyneurotek Pharmaceuticals Ag

Esparma Gmbh

Serumwerk Bernburg Ag

Institut Fur Medizintechnologie Magdeburg (imtm) Gmbh

Siegfried Ansorge

Klaus Neubert

Uwe Lendeckel

Dirk Reinhold

Harald Gollnick

Robert Vetter

Michael Täger

Gerhard Fries

Frank Striggow

Dieter Koegst

Michael Taeger

Ute Bank

Klaus G Reymann

Peter Röhnert

Jürgen Faust

Marco Arndt

Frank Buehling

Stefan Brocke

Janine Tadje

Christos Zouboulis

Ulrich Schröder

Karsten Nordhoff

Bianca Senns

Petra Fuchs

Irene Reichstein

Compounds of the general formulae (1) and (2)A-B-D-B'-A&#x2032;&#x2003;&#x2003;(1)andA-B-D-E&#x2003;&#x2003;(2)in which 

Dual-use peptidase inhibitors as prodrugs for a therapy of inflammatory and other diseases

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).

Dual alanyl aminopeptidase and dipeptidyl peptidase iv inhibitors for functionally influencing different cells and for treating immunological inflammatory, neuronal and other diseases

The present invention concerns the use of Provided is a drug composition and a method for using the composition for the prevention and the therapy of neurodegenerative diseases. The combination comprises at least two of the following substances: &#x3b1;-lipoic acid; ambroxol and one or several inhibitor(s) of the angiotension-converting enzyme (ACE).

Drug preparation comprising &#x3b1;-lipoic acid, ambroxol and/or inhibitors of the angiotensin-converting enzyme (ACE) and its use for the treatment of neurodegenerative diseases

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.

Combined use of enzyme inhibitors and of pharmaceutical compositions thereof

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.

Use of enzyme inhibitors of aminopeptidase N and/or dipeptidylpeptidase IV

The invention relates to the use of the combination of n-lipoic acid and effectors of the glutathione metabolism for the treatment of disturbances of the cellular thiol status and accompanying disorders in kidney replacement therapy.

Use of a medicament containing an effector of the glutathione metabolism together with &#x3b1;-lipoic acid in kidney replacement therapy

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.

Combinations of enzyme inhibitor-containing preparations and the use thereof

The invention relates to a medicament containing an effector of the glutathione metabolism together with &#x3b1;-lipoic acid for treating diabetes mellitus. This medicament enables disturbances of the thiol-disulfide status or those that occur, for example, in diabetes mellitus to be treated simultaneously, separately or in a temporally graduated manner.

Medicament containing an effector of the glutathione metabolism together with &#x3b1;-lipoic acid for treating diabetes mellitus

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-&#x3b2;1 and of the expression of TGF-&#x3b2;1 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.

Use of alanyl aminopeptidase inhibitors and pharmaceutical compositions containing said inhibitors

Combination of inhibitors of dipeptidyl peptidase IV (DP IV) and 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) for 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.

Combinations of enzyme inhibitors and the use thereof

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Hohenwarthe, Germany

Siegfried Ansorge