التفاصيل البيبلوغرافية
| العنوان: |
Combined use of enzyme inhibitors and of pharmaceutical compositions thereof |
| Document Number: |
20070249541 |
| تاريخ النشر: |
October 25, 2007 |
| Appl. No: |
11/811565 |
| Application Filed: |
June 11, 2007 |
| مستخلص: |
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. |
| Inventors: |
Ansorge, Siegfried (Hohenwarte, DE); Lendeckel, Uwe (Magdeburg, DE); Neubert, Klaus (Halle, DE); Reinhold, Dirk (Magdeburg, DE); Vetter, Robert (Magdeburg, DE); Gollnick, Harald (Magdeburg, DE) |
| Claim: |
1. A method for producing in an individual a more than additive to superadditive inhibition of the activation, proliferation (DNA-synthesis) and production of TH2 cytokines of human T lymphocytes and mononuclear cells comprising administering to the individual an effective amount of a composition comprising an inhibitor of dipeptidyl peptidase IV (DP IV) as well as of enzymes having the same substrate specificity (DP IV-analogous enzymatic activity) in combination with an inhibitor of alanylamino-peptidase (aminopeptidase N, APN) as well as of enzymes having the same substrate specificity (APN-analogous enzymatic activity). |
| Claim: |
2. The method according to claim 1, wherein the inhibitor of DP IV is selected from the group consisting of: amino acid (Xaa)-Pro-dipeptides or corresponding derivatives, wherein Xaa is an α-amino acid or side chain protected derivative; and Xaa-Xaa-(Trp)-Pro-(Xaa)n peptides, corresponding derivatives or salts thereof, wherein Xaa is an α-amino acid and n is an integer from 0 to 10; and Xaa-amides, corresponding derivatives and salts thereof, wherein Xaa is an α-amino acid or a side chain protected derivative and wherein cyclic amines and their derivatives serve as the amide structure; and combinations thereof. |
| Claim: |
3. The method according to claim 2, wherein the Xaa-Pro-dipeptide is selected from dipeptide phosphonic acid diaryl ester, or a dipeptide boronic acid and salts thereof. |
| Claim: |
4. The method according to claim 3, wherein the dipeptide boronic acid is Pro-Boro-Pro. |
| Claim: |
5. The method according to claim 2, wherein the amino acid of the amino acid (Xaa)-amide is selected from N-4-nitrobenzyloxycarbonyl-L-lysine, L-proline, L-tryptophane, L-isoleucine and L-valine. |
| Claim: |
6. The method according to claim 2, wherein the cyclic amine is selected from pyrrolidine, piperidine and thiazolidine. |
| Claim: |
7. The method according to claim 2, wherein the amino acid (Xaa)-amide is selected from the group consisting of Nε-4-nitrobenzyloxycarbonyl-L-lysine thiazolidide, Nε-4-nitrobenzyloxycarbonyl-L-lysine pyrrolidide, Nε-4-nitrobenzyloxy-carbonyl-L-lysine, N-4-nitrobenzyloxycarbonyl-L-lysine piperidide, Nε-4-nitrobenzyloxycarbonyl-L-lysine 2-cyanothiazolidide, Nε-4-nitrobenzyloxycarbonyl-L-lysine 2-cyanopyrrolidide and Nε-4-nitrobenzyloxycarbonyl-L-lysine 2-cyanopiperidide. |
| Claim: |
8. The method according to claim 1, wherein the inhibitor of APN is selected from the group consisting of Actinonin, Leuhistin, Phebestin, Amastatin, Bestatin, Probestin, RB3014, β-aminothiols, α-aminophosphinic acids, α-aminophosphinic acid derivatives and salts thereof. |
| Claim: |
9. The method according to claim 8, wherein the α-aminophosphinic acid derivative is D-Phe-ψ[PO(OH)—CH2]-Phe-Phe or salts thereof. |
| Claim: |
10. The method according to claim 1, wherein the administration results in prevention or therapy of allergic reactions of type I. |
| Claim: |
11. The method according to claim 10, wherein the administration results in prevention or therapy of asthma bronchiale or hay fever. |
| Claim: |
12. The method according to claim 1, wherein the composition is administered by a route selected from oral, transdermal, intravenous, subcutaneous, intracutaneous, intramuscular, rectal, vaginal and sublingual. |
| Claim: |
13. The method according to claim 1, wherein the composition is administered topically as a cream, ointment, paste, gel, solution, spray, liposome, shaken mixture, hydro-colloid dressing or other dermatological bases/vehicles including instillative application. |
| Claim: |
14. The method according to claim 1, wherein two or more inhibitors of DP IV as well as of an inhibitor of an enzyme having DP IV-analogous enzymatic activity and of alanyl-aminopeptidase (aminopeptidase N, APN) as well as of an inhibitor of an enzyme having APN-analogous enzymatic activity are in a compartimentally separate formulation in combination with known carrier, auxiliary and/or additive substances for a simultaneous or immediately timely consecutive administration with the aim of a combined effect. |
| Claim: |
15. The method according to claim 14, wherein the inhibitor of DP IV is selected from the group consisting of: amino acid (Xaa)-Pro-dipeptides or corresponding derivatives, wherein Xaa is an α-amino acid or side chain protected derivative; and Xaa-Xaa-(Trp)-Pro-(Xaa)n peptides, corresponding derivatives or salts thereof, wherein Xaa is an α-amino acid and n is an integer from 0 to 10; and Xaa-amides, corresponding derivatives and salts thereof, wherein Xaa is an oβ-amino acid or a side chain protected derivative and wherein cyclic amines and their derivatives serve as the amide structure; and combinations thereof. |
| Claim: |
16. The method according to claim 15, wherein the Xaa-Pro-dipeptide is selected from dipeptide phosphonic acid diaryl ester, or a dipeptide boronic acid and salts thereof. |
| Claim: |
17. The method according to claim 15, wherein the amino acid of the amino acid (Xaa)-amide is selected from Nε-4-nitrobenzyloxycarbonyl-L-lysine, L-proline, L-tryptophane, L-isoleucine and L-valine. |
| Claim: |
18. The method according to claim 14, wherein the inhibitor of APN is selected from the group consisting of Actinonin, Leuhistin, Phebestin, Amastatin, Bestatin, Probestin, RB3014, β-aminothiols, α-aminophosphinic acids, α-aminophosphinic acid derivatives and salts thereof. |
| Claim: |
19. The method according to claim 8, wherein the α-aminophosphinic acid derivative is D-Phe-ψ[PO(OH)—CH2]-Phe-Phe or salts thereof. |
| Claim: |
20. The method according to claim 14, wherein the administration results in prevention or therapy of allergic reactions of type I, and/or prevention or therapy of asthma bronchiale or hay fever. |
| Current U.S. Class: |
514019/000 |
| Current International Class: |
61; 61; 61; 61; 61; 61 |
| رقم الانضمام: |
edspap.20070249541 |
| قاعدة البيانات: |
USPTO Patent Applications |