Preparations comprising combinations of enzyme inhibitors,...

Details Preparations comprising combinations of enzyme inhibitors,... Preparations comprising combinations of enzyme inhibitors,...

A - Human Necessities

61

K

A61K 45/06 (2006.01) A61K 38/55 (2006.01) A61P 35/00 (2006.01) A61P 37/06 (2006.01)

Patent

CA 2410305

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; (Ir) of dipeptidyl peptidase IV and of the angiotensin-converting enzyme; (III) of dipeptidyl peptidase IV and of prolyl oligopeptidase; and (IV) of di-peptidyl 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.

L'invention concerne un procédé permettant, grâce à l'inhibition simultanée et commune des activités enzymatiques de la (I) alanylaminopeptidase et de la dipeptidylpeptidase IV, de la (II) dipeptidylpeptidase IV et de l'enzyme de conversion de l'angiotensine, de la (III) dipeptidylpeptidase IV et de la prolyloligopeptidase, ainsi que (IV) de la dipeptidylpeptidase IV et de la X-pro-aminopeptidase, d'inhiber la synthèse d'ADN et ainsi la prolifération de cellules mononucléaires et également de cellules T, à un degré encore jamais atteint par l'administration individuelle de ces inhibiteurs enzymatiques, même à de fortes doses. Bien que les inhibiteurs susmentionnés influent finalement sur le même processus, à savoir la synthèse d'ADN et donc la prolifération de cellules immunitaires, cet effet, lors de l'administration des inhibiteurs, n'est ni complet ni durable. Du recoupement fonctionnel des activités enzymatiques, il résulte, comme nos informations le montrent, un effet inhibiteur additif/superadditif sur la synthèse d'ADN et la prolifération de cellules immunitaires, lors des inhibitions simultanées de plusieurs des enzymes susmentionnées. Notre invention montre que, pour la thérapie de maladies autoimmunes et chroniques à genèse inflammatoire, ainsi que pour le traitement d'épisodes de rejet consécutifs à des transplantations, on peut administrer simultanément des inhibiteurs des enzymes susmentionnés ou des préparations ou formes d'administration correspondantes.

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