Kostengünstige Sprays bei Psoriasis Kostengünstige Sprays bei Psoriasis


Kostengünstige Sprays bei Psoriasis EPA2 - Diaminosäurederivate und pharmazeutische Zusammensetzungen - Google Patents

The invention relates to the use of inhibitors of dipeptidyl peptidase IV DP IV and enzymes having the same specific nature of substrate DP IV enzyme activitycombined with inhibitors of alanyl aminopeptidase aminopeptidase N, APNor enzymes having the same specific nature of substrate APN enzyme Try the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.

Combined use of enzyme inhibitors for the treatment and prevention of allergic reactions of type i according to the gell and coombs classification, and for the treatment and prevention of dermatological diseases associated with follicular kostengünstige Sprays bei Psoriasis epidermal hyperkeratosis and reinforced keratinocyte proliferation EP B1. The invention kostengünstige Sprays bei Psoriasis to the use of inhibitors of dipeptidyl peptidase IV DP IV and enzymes having the same specific nature of substrate DP IV enzyme activitycombined with inhibitors of alanyl aminopeptidase aminopeptidase N, APNor enzymes having the same specific nature of substrate APN enzyme activityfor the additive to superadditive inhibition of the activation and proliferation DNS synthesis of human T lymphocytes or mononuclear cells and of the production of TH2 cytokines for the treatment and prevention of allergic reactions of type I according to the Gell and Coombs classification, for the additive to superadditive inhibition of the activation and proliferation DNS synthesis of human epidermal and follicular more info and those of the transitional region between the skin and the mucosa, and for the treatment and prevention of dermatological diseases associated with follicular and epidermal hyperkeratosis and reinforced keratinocyte proliferation.

The invention further relates to pharmaceutical preparations comprising a plurality of inhibitors of enzymes of the above-mentioned groups. The use according to claim 1 or claim 2, wherein the Xaa-Pro-dipeptide is selected from the group consisting of kostengünstige Sprays bei Psoriasis phosphonic acid diaryl esters and dipeptide boronic acids.

The use according to claim 3, wherein the dipeptide boronic acid is Pro-Boro-Pro. The use according to claim 1 or claim 2, wherein the cyclic amine is selected from the group consisting of pyrrolidine, piperidine and thiazolidine.

The use according to any of claims 1 to 7, wherein the DP IV inhibitor is Lys[Z NO 2 ]-thiazolidide, wherein Lys is a L-lysine residue and Z NO 2 is 4-nitrobenzyloxycarbonyl. The use according to any of claims 1 and 3 to 9 for the prevention and therapy of asthma bronchiale or hay fever. The use according to any of claims 1 to 11 for a systemic application for an oral, transdermal, intravenous, subcutaneous, intracutaneous, intramuscular, rectal, vaginal or sublingual administration.

The use according to any of claims 1 to 13, wherein the inhibitor of the dipeptidyl peptidase IV DP IV or the inhibitor of enzymes having a similar substrate specificity DP IV-analogous enzymatic activity and the inhibitor of alanyl-aminopeptidase aminopeptidase N, APN or the inhibitor of enzymes having similar substrate specificity APN-analogous enzymatic activity in a compartmentally separate formulation are to be administered simultaneously or consecutively in time with the aim of a combined effect.

Die Erfindung betrifft die Source der DNS-Synthese und damit der Proliferation von Immunzellen durch die kombinierte Wirkung von Inhibitoren der Aminopeptidase N APN, EC3.

The invention relates to the inhibition of DNA synthesis and thus the proliferation of immune cells by the combined effect of inhibitors of the aminopeptidase N APN, EC3. The invention also relates to the inhibition of proliferation necessary for the DNA synthesis and cytokine production IL-4, IL-4 of T H2 cells by the combined effect of inhibitors of the aminopeptidase N APN, EC3.

The invention also relates to the inhibition of proliferation necessary for the DNA synthesis of keratinocytes by the combined kostengünstige Sprays bei Psoriasis of inhibitors of the aminopeptidase Kostengünstige Sprays bei Psoriasis APN, EC3. Steinmetzer Torsten et al. Enzyme Inhibition 14describes the property of molecules with a cyclic imide skeleton as aminopeptidase inhibitors.

Biochim Acta 50describes the role of two enzymes, namely the two peptidases DP IV and APN, in the organism as well as their separate inhibition. Journal of RheumatologyVol 44, No. Applies to all go here with autoimmune pathogenesis that activation and proliferation of immune cells, particularly of autoreactive T-cells, the disease process underlying or make them. Similar mechanisms are used in a number of inflammatory kostengünstige Sprays bei Psoriasis such as atherosclerosis effect, where T kostengünstige Sprays bei Psoriasis play a central role in origination and chronicity of the disease process.

CD26 a surface protease involved in T-cell activation. It has been shown that in the process of activation and clonal expansion of immune cells, especially T lymphocytes, membrane-bound peptidases as DP IV or APN play a key role [Fleischer B: CD26 a surface protease Involved in T-cell activation. Immunology Today ; Immunology Today ; Role of alanyl aminopeptidase in growth and function of human T cells.

International Journal of Molecular Medicine ; International Journal of Molecular Medicine 4: CD13 - not just a marker in leukemia typing. Immunology Today ; Immunology Today The dipeptidyl peptidase IV, a kostengünstige Sprays bei Psoriasis enzyme involved in the proliferation of T lymphocytes. The dipeptidyl peptidase IV, a membrane enzyme Involved in the proliferation of T lymphocytes. Acta ; Acta, ; 2: The role of dipeptidyl peptidase IV in human T lymphocyte activation.

Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro. Inhibitor and dipeptidyl peptidase IV suppress antibodies against lymphocyte proliferation and immunoglobulin synthesis in vitro. Immunology ; Immunology ; Induction of the membrane alanyl aminopeptidase gene and surface expression in human T-cells by mitogenic activation. A cell surface peptidase involved in regulating T cell growth Review. A cell surface peptidase Involved in regulating T cell growth Review.

Role of alanyl aminopeptidase kostengünstige Sprays bei Psoriasis growth and function of human T cells Review. Atherosclerosis- an inflammatory disease. On the other hand, kostengünstige Sprays bei Psoriasis findings in recent years have atherosclerosis characterized as an inflammatory disease in which T lymphocytes a crucial role in the emergence and development of the disease plays [Ross R: Atherosclerosis- to inflammatory disease.

Accordingly atherosclerotic lesions to be understood as a series of specific cellular and molecular reactions that are taken together clearly be characterized as inflammation. The role of rheology in atherosclerotic coronary artery disease. Atherosclerotic lesions are formed at defined arterial places where branches and curves characteristic changes in blood flow and shear forces as well as the formation of turbulence effect [Gotlieb AI, et al.: Fuster V, Ross R, Topol EJ, eds.

Atherosclerosis and coronary athery disease. Atherosclerosis and coronary disease athery. Vascular endothelial cells then form specific molecules, which are responsible for the attraction, binding, accumulation and activation of T lymphocytes and monocytes in these places. T-Lymphozyten sind wesentliche inflammatorische Zellen in allen Phasen der Atherogenese. T lymphocytes are key inflammatory cells in all phases of atherogenesis. Regional accumulation of T cells, macrophages and smooth muscle cells in the human atherosclerotic plaque.

T cells infiltrate from the peripheral blood in atherosclerotic plaques and http://festival-celle.de/psoriasis-salbe-advantan-1.php multiply at the site of the lesion [Jonasson L, et al.: Regional accumulation of T cells, macrophages and smooth muscle cells in human atherosclerotic plaque the.

Atherosclerotic lesions in humans: Cytokines and growth go here molecules. As a result of this accumulation of activated T-lymphocytes, which are characterized by a strong expression of alanyl aminopeptidase and dipeptidyl peptidase IV, at the site of atherosclerotic lesion chemokines, cytokines, growth factors and proteases are released, which lead to further enhancement of the disease by other are recruited and activated immune cells [Libby P and Ross R.

Auch Monozyten, die kostengünstige Sprays bei Psoriasis atherosklerotischen Plaques lokalisiert sind, zeichnen sich durch die konstitutive Expression von z. Alanylaminopeptidase APN aus und sind, wie http://festival-celle.de/als-unterscheidet-sich-von-psoriasis.php Arbeiten zeigen, nachhaltig durch Hemmstoffe der oben beschriebenen Enzyme in ihrem Wachstum und ihrer Funktion zu supprimieren.

Kostengünstige Sprays bei Psoriasis, which are located in atherosclerotic plaques are characterized by the constitutive expression continue reading z. The same applies to endothelial cells, which also express this ectopeptidases.

Dem Angiotensin-konvertierenden Enzym kommt eine besondere Rolle in der Pathogenese der Atherosklerose zu: Dieses Enzym bewirkt die Bildung des stark blutdrucksteigernden Angiotensin Kostengünstige Sprays bei Psoriasis Ang II aus dem Ang Kostengünstige Sprays bei Psoriasis. The angiotensin-converting enzyme has a specific role in the pathogenesis of atherosclerosis: This enzyme causes the formation of strong pressor angiotensin II Ang II from Ang I.

Hypertension is an important risk factor for atherosclerosis and affected patients often have elevated Ang II mirrors. In addition, Ang II is proatherogen by the growth of smooth muscle vessels stimulates [Chobanian AV et al. Renin angiotensin system kostengünstige Sprays bei Psoriasis atherosclerotic vascular disease. Kostengünstige Sprays bei Psoriasis smooth muscle cell hypertrophy vs. Ang II increases the inflammatory response in addition also on the increase of lipoxygenase activity whereby inflammatory mediators are released amplified.

Grover, vitiligo and hyperproliferation of keratinocytes associated erythroderma. Bevorzugt finden sie Anwendung bei der Vorbeugung und Therapie von Asthma bronchiale oder Heuschnupfen. According to the inventive use the inhibitor combinations are used in accordance with kostengünstige Sprays bei Psoriasis above information for prevention and therapy of allergic-type reactions I. Preferably, they are used in the prevention and treatment of asthma or hay fever.

Although kostengünstige Sprays bei Psoriasis inhibitors finally influence the same process, namely the DNA synthesis and thus the proliferation of immune cells, this effect kostengünstige Sprays bei Psoriasis much less pronounced and not permanently on individual application of the inhibitors. Because of the functional overlap between the enzymatic activities of these enzymes result, as our data show, an additive to super additive inhibitory effect on DNA synthesis and proliferation of the simultaneous inhibition of two or more of these enzymes.

The invention shows that for the therapy kostengünstige Sprays bei Psoriasis autoimmune diseases and inflammatory diseases such as kostengünstige Sprays bei Psoriasis, for the origination proliferation and kostengünstige Sprays bei Psoriasis of T lymphocytes play a central role has importance, the simultaneous application of inhibitors of the abovementioned enzymes or corresponding preparations and dosage forms thereof are suitable.

The application of enzyme inhibitors represents a novel method and complementary form of therapy for these diseases. According to the invention applied inhibitors of dipeptidyl peptidase IV and the aminopeptidase N, can be applied in pharmaceutically acceptable formulation complexes as inhibitors, substrates, pseudosubstrates, acting inhibitory peptides and peptide derivatives of this enzyme. The inhibitors are administered simultaneously with known carriers.

Induction and regulation of kostengünstige Sprays bei Psoriasis IgE response. Applies to all Type I allergic reactions such as asthma or hay fever that activation, proliferation and cytokine production especially IL-4 is based on immune cells, especially T H2 cells, the disease process [DD Corry et al.: Nature ; Nature ; On the other hand, scientific findings in recent years kostengünstige Sprays bei Psoriasis the allergic reaction characterized type I as a disease in which the T H2 lymphocytes play a crucial role in the emergence and chronicity of kostengünstige Sprays bei Psoriasis disease [DD Corry et al.: Therapeutic strategies for allergic diseases.

IL-4 stellt ein Helferzytokin der B-Zell-Proliferation dar, stimuliert die Bildung von IgE und die Expression niedrigaffiner Here. IL-4 is a Helferzytokin of B-cell proliferation, stimulates the formation of IgE, and the expression niedrigaffiner IgE Fc receptors. In addition, IL-4 enhances the induction of T H2 kostengünstige Sprays bei Psoriasis themselves and controls the proliferation and activity of eosinophils and mast cells.

Damit spielt kostengünstige Sprays bei Psoriasis eine zentrale Rolle bei allergischen Reaktionen vom Typ I [ DP Stites, AI Terr, TG Kostengünstige Sprays bei Psoriasis Thus, it plays a central role in allergic reactions of type I [DP Stites, AI Terr, TG Parslow: Although the so-called inhibitors ultimately the same processes, namely, the DNA synthesis and influence the proliferation and IL-4 production of T H2 cells, this effect is much less pronounced and not permanently in single application of the inhibitors.

Due to the functional overlap of the enzymatic activities of these enzymes results, as our data show an additive to super-additive inhibitory effect on DNA synthesis and proliferation from the simultaneous inhibition kostengünstige Sprays bei Psoriasis both enzymes.

Our invention shows that for the treatment of allergic type I reactions to arise from the proliferation and activation of T lymphocytes H2 is of central importance, the simultaneous application of inhibitors of DP IV and APN or kostengünstige Sprays bei Psoriasis formulations and dosage forms of it are suitable. In detail, the invention based on the findings that DNA synthesis and IL-4 production by MNC by the simultaneous administration of inhibitors of dipeptidyl peptidase IV and enzymes having the same substrate kostengünstige Sprays bei Psoriasis DPIV-like enzyme activity and aminopeptidase N and enzymes with the same substrate specificity APN-analogous enzyme activity is inhibited in an additive to super-additive manner.

According to the invention applied inhibitors of dipeptidyl peptidase IV and the aminopeptidase N may be employed in pharmaceutically acceptable formulation complexes as inhibitors, substrates, pseudosubstrates, acting inhibitory peptides and peptide derivatives of this enzyme. A number of dermatologic diseases are associated with follicular and epidermal hyperkeratosis and increased keratinocyte proliferation.

They include both inflammatory and non-inflammatory epidermal hyperproliferation conditions eg. As congenital ichthyosis and psoriasisbenign and malignant clonal expansions circumscribed epidermal z. Keratosis follicularis example as well as benign and malignant epithelial adnexal tumors and primary and reactive nail cell hyperproliferations.

A Detailed information on this is kostengünstige Sprays bei Psoriasis in Table 1. Proline-dependent structural and biological properties of peptides and proteins.

Peptidases such as dipeptidyl peptidase IV and aminopeptidase N or similarly acting enzymes are of particular interest because they are localized inter alia, as ectoenzymes in the plasma membrane of cells that undergo interactions with other extracellular structures, peptidergic neurotransmitters in the regulation or modulation of interactions between cells by activate or inactivate enzyme-catalyzed hydrolysis and therefore are important for cell-cell communication [Yaron A, et al.: Crit Rev Biochem Mol Kostengünstige Sprays bei Psoriasis ; Proline motifs in peptides and their biological processing.

Crit Rev Biochem Mol Biol click at this page Proline motifs in peptides and Their biological processing. FASEB J ; 9: It is already known that the treatment of autoimmune diseases and transplant rejection by inhibiting localized on immune cells, dipeptidyl peptidase IV using synthetic inhibitors is possible eg.

EP A1 EP A1. Although the above inhibitors ultimately the same processes, namely the DNA synthesis and thus affect the proliferation of keratinocytes, this effect is less pronounced and not permanently in single application of the inhibitors.

Due to the functional overlap of the enzymatic activities of kostengünstige Sprays bei Psoriasis enzymes results, as our data show an additive and at lower concentrations an additive to super-additive inhibitory effect on DNA synthesis and proliferation from the simultaneous inhibition of both enzymes. Our invention shows that for the treatment and prevention Psoriasis trinken Kwass both inflammatory and non-inflammatory epidermal hyperproliferation conditions eg.

In addition to keratinocytes and T lymphocytes play in inflammatory diseases of the skin, especially in autoimmune diseases such as psoriasis, a central role.

T-Zellen exprimieren wie Keratinozyten die hier behandelten Peptidasen DP IV und APN. T-cells express such as keratinocytes treated here peptidases DP IV and APN. It follows that the therapeutic effect that is claimed herein or protected for the cell type keratinocytes, is amplified by influencing the T-cells continue see patent application DE Cyclosporin A, Kortikosteroide, Retinoide behandelt.

The above-mentioned diseases are far topically with antiproliferative and differentiating agents salicylic acid, urea, endogenous and synthetic retinoids, vitamin D3 kostengünstige Sprays bei Psoriasis, corticosteroids and systemically with z. Particularly in the case of the systemic use occur frequently undesirable side effects.

The combined use of DP IV and APN inhibitors would represent a novel vorraussichtlich very effective, cost-effective form of therapy and may be a valuable alternative component of existing therapy concepts in these diseases. The present invention applied inhibitors of dipeptidyl peptidase IV and of Enymen with the same substrate specificity DP IV-like enzyme activity and aminopeptidase N or of enzymes having a similar substrate specificity APN-analogous enzyme activity may in pharmaceutically applicable formulation complexes as inhibitors, substrates, pseudo substrates, inhibitory effect peptides and peptide kostengünstige Sprays bei Psoriasis of these enzymes are used.

Preferred inhibitors are, for example, for DP IV Xaa-Pro dipeptides, corresponding derivatives, preferably dipeptide, dipeptide boronic acids z. Preferred inhibitors of alanyl aminopeptidase are bestatin Ubenimexactinonin, probestin, phebestin, RB or leuhistin. Darier Lichenoide Reaktionen bei GvHD Lichenoid reactions in GVHD - Epidermale Naevi - Epidermal nevi - ILVEN-Naevus - ILVEN Nevus - Cutis rhomboidalis nuchae - Cutis rhomboidalis nuchae - Lupus erythematodes chron.

The invention is further illustrated by the following examples, without being limited thereto. In den Beispielen wird auf Abbildungen 1 bis 14 Bezug genommen. In the examples reference is made to Figures 1 to 14 reference. Synergistic and dose-dependent effect of inhibitors of DP IV I49 and aminopeptidase N actinonin on the DNA synthesis of human T-lymphocytes.

Human peripheral T cells were incubated for three days with the indicated concentrations of inhibitors. Subsequently, the culture kostengünstige Sprays bei Psoriasis was 3 [H] -methyl-thymidine was added and after a further 6 hours, the built-in DNS amount of 3 [H] thymidine was measured. Kostengünstige Sprays bei Psoriasis and dose-dependent effect of inhibitors of DP IV I49 and the APN Actinonin on the DNA synthesis of human mononuclear cells MNC.

Human MNC were incubated for three days with the indicated concentrations of inhibitors. Synergistic and dose-dependent effect of inhibitors of DP IV I49 and the prolyl oligopeptidase Boc-Ala-Thia on the DNA synthesis of human peripheral T-lymphocytes. Human T cells were incubated for three days with the indicated concentrations of inhibitors. Reinforced and dose-dependent effect of inhibitors of DP IV I49 and the prolyl oligopeptidase Boc-Ala-Thia on the DNA synthesis of human mononuclear cells MNC.

Subsequently, the culture medium 3 kostengünstige Sprays bei Psoriasis incorporated into DNA, the amount of 3 [H] thymidine was added and after a further 6 hours measured. Synergistic and dose-dependent effect of inhibitors of DP IV I49 and the angiotensin-converting enzyme captopril on the DNA synthesis of human peripheral T-lymphocytes. Synergistic and dose-dependent effect of inhibitors of DP IV I49 and the angiotensin-converting enzyme inhibitors captopril on the DNA synthesis of human kostengünstige Sprays bei Psoriasis cells MNC.

The MNC were incubated for 72 h without addition controlwith the mitogenic lectin phytohaemagglutinin PHA or with PHA and the indicated inhibitors.

Then determining the number of metabolically active cells using the commercially available WST-1 cell proliferation assay Takara Inc. The KARPAS cells were incubated for 72 h without addition control or in the presence of the indicated inhibitors individually and in combination. The T cells were activated with the exception of the untreated control kostengünstige Sprays bei Psoriasis adding to the culture medium of phytohemagglutinin and phorbol myristate acetate and incubated in combination over a kostengünstige Sprays bei Psoriasis of 72 h in the presence of the indicated inhibitors individually as well.

The mononuclear cells MNC were incubated in combination over a period of 72 h in the presence of the indicated inhibitors individually as well.

Synergistic and dose-dependent effect of kostengünstige Sprays bei Psoriasis of DP IV I49 and aminopeptidase Source bestatin on kostengünstige Sprays bei Psoriasis DNA synthesis of human PWM-stimulated PBMCs.

Synergistic and dose-dependent effect of inhibitors of DP IV I49 and aminopeptidase Kostengünstige Sprays bei Psoriasis bestatin on IL-4 production of kostengünstige Sprays bei Psoriasis, PWM-stimulated MNC.

The concentrations of IL-4 in the corresponding culture supernatants were then measured by IL-4 ELISA. Nachweis der mRNA-Expression von DP IV und APN auf HaCaT-Keratinozyten mittels RT-PCR Detection of mRNA expression of DP IV and APN on HaCaT keratinocytes by RT-PCR Abb. Synergistic and dose-dependent effect of inhibitors of DP IV I49 and aminopeptidase N Actinonin on the DNA synthesis of human HaCaT keratinocytes. The cells were incubated for 48 kostengünstige Sprays bei Psoriasis with kostengünstige Sprays bei Psoriasis indicated concentrations of inhibitors.

The T cells were incubated in the presence of said inhibitors, and thereafter -thymidine incorporation determined the DNA synthesis by measuring the 3 [H], as described by Reinhold et al 72 h.

The MNC were incubated in the presence of 72 and then -thymidine incorporation determined the DNA synthesis by measuring the 3 [H], as described by Reinhold et al of the above inhibitors h. Abbildung 7 Figure 7: And APN Actinonin and probestin Abbildung 8 Figure 8: Hemmung der Proliferation aktivierter, humaner peripherer T-Zellen durch die einzelne bzw. And APN Actinonin and probestin Abbildung 9 Figure 9: Abbildung 10 Figure The MNC were 72 h in the presence of pokeweed mitogen and of kostengünstige Sprays bei Psoriasis inhibitors, incubated and then PUVA-Therapie Psoriasis das wird helfen incorporation determined the DNA synthesis by measuring the 3 [H], as described by Reinhold et al.

The MNC were incubated and then using commercial ILdetermining kit ELISAthe concentrations of IL-4 in the corresponding culture supernatants determined as described by Reinhold et al in the presence of pokeweed mitogen and of said inhibitors for 48 kostengünstige Sprays bei Psoriasis. The human keratinocyte HaCat, which is accepted as a cell model for psoriasis, expressed DP IV and APN. The enzymatic activity of DP IV of vital cells is Entsprechend ist die mRNA von APN und DP IV auf diesen Zellen nachweisbar Accordingly, the mRNA of APN and DP IV is detectable in these cells Abb.

HaCaT cells were incubated for 48 h with the inhibitors mentioned above and then -thymidine incorporation determined the DNA synthesis by measuring the 3 [H], as described by Reinhold et al.

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Kostengünstige Sprays bei Psoriasis

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The invention relates to the use of inhibitors of dipeptidyl peptidase IV (DP IV) and enzymes having the same specific nature of substrate (DP IV enzyme activity.
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