USE OF INHIBITORS OF DIPEPTIDYL PEPTIDASE IV (DP IV) IN COMBINATION WITH INHIBITORS OF ALANYL-AMINOPEPTIDASE (APN)

摘要

Combined Use of Enzyme Inhibitors and of Pharmaceutical Compositions thereoffor a Therapy and a Prophylactic Treatment of Arteriosclerosis, for a TherapyandPrevention of Allergic Reactions of the Type I according to the Gell andCoombsClassification and for a Therapy and Prevention of Dermatological DiseaseswithFollicular and Epidermal Hyperceratoses and an Enhanced Proliferation ofKeratinocytesThe present invention relates to the use of inhibitors of dipeptidyl peptidaseIV (DP IV)and of enzymes having the same substrate specifity (DP IV-analogous enzymaticactivity)in combination with inhibitors of alanyl aminopeptidase (aminopeptidase N,APN)and of enzymes having the same substrate specifity (APN-analoguos enzymaticactivity)for a more than additive to superadditive inhibition of the activation andproliferation(DNA synthesis) of human T lymphocytes and mononuclear cells and of theproductionof T H2 cytokines for a therapy and prevention of allergic reactions of thetype Iaccording to the Gell and Coombs classification and for a more than additiveto superadditiveinhibition of the activation, proliferation (DNA synthesis) of human epidermaland follicular keratinocytes and of keratinocytes of the transitional zonebetween theskin and the mucous membranes as well as for a therapy and prevention ofdermatologicaldiseases with follicular and epidermal hyperkeratoses and an enhancedproliferationof keratinocytes. The invention also relates to the use of inhibitors ofdipeptidyl peptidaseIV (DP IV) as well as of enzymes having the same substrate specifity (DP IV--analogousenzymatic activity) in combination with inhibitors of alanyl aminopeptidase(aminopeptidase N, APN) and of enzymes having the same substrate specifity(APN--analogousenzymatic activity), respectively, of X-Pro-aminopeptidase (aminopeptidaseP, APP), of the "angiotensin-converting enzyme" (ACE) and/or of the prolyloligopeptidase(POP, prolyl endopeptidase, PEP) for a more than additive to superadditiveinhibitionof activation, DNA synthesis and proliferation of human T lymphocytes andmononuclearcells for a therapy and prophylaxis of arteriosclerosis. The invention alsorelatesto pharmaceutical preparations comprising more than one of said inhibitors ofenzymesof the above group.