NL194153C - Preparation intended for the prophylaxis or treatment of protozoan infections in animals. - Google Patents
Preparation intended for the prophylaxis or treatment of protozoan infections in animals. Download PDFInfo
- Publication number
- NL194153C NL194153C NL8102863A NL8102863A NL194153C NL 194153 C NL194153 C NL 194153C NL 8102863 A NL8102863 A NL 8102863A NL 8102863 A NL8102863 A NL 8102863A NL 194153 C NL194153 C NL 194153C
- Authority
- NL
- Netherlands
- Prior art keywords
- dfmo
- combination
- bleomycin
- composition
- dose
- Prior art date
Links
- 241001465754 Metazoa Species 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 13
- 238000011282 treatment Methods 0.000 title claims description 9
- 238000011321 prophylaxis Methods 0.000 title claims description 6
- 208000010362 Protozoan Infections Diseases 0.000 title description 5
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 16
- 108010006654 Bleomycin Proteins 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 229960001561 bleomycin Drugs 0.000 claims description 8
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 241000223105 Trypanosoma brucei Species 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- -1 procarbozine Chemical compound 0.000 claims description 4
- 241000283690 Bos taurus Species 0.000 claims description 3
- 230000003071 parasitic effect Effects 0.000 claims description 3
- 208000000230 African Trypanosomiasis Diseases 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 claims description 2
- 239000003904 antiprotozoal agent Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 239000002532 enzyme inhibitor Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 4
- 239000003651 drinking water Substances 0.000 claims 3
- 235000020188 drinking water Nutrition 0.000 claims 3
- KRUVSRGJKCHYMY-UHFFFAOYSA-N 1,3-bis(3-carbamimidoylphenyl)urea Chemical compound NC(=N)C1=CC=CC(NC(=O)NC=2C=C(C=CC=2)C(N)=N)=C1 KRUVSRGJKCHYMY-UHFFFAOYSA-N 0.000 claims 2
- KMJWBVJQFGRCEB-UHFFFAOYSA-O 4-n-(4-imino-1,2-dimethylquinolin-6-yl)-1,6-dimethylpyrimidin-1-ium-2,4-diamine Chemical compound C=1C=C2N(C)C(C)=CC(=N)C2=CC=1NC1=CC(C)=[N+](C)C(N)=N1 KMJWBVJQFGRCEB-UHFFFAOYSA-O 0.000 claims 2
- WZIPHSLUGLMTRU-UHFFFAOYSA-N 6-n-(2-amino-1,6-dimethylpyrimidin-1-ium-4-yl)-1,2-dimethylquinolin-1-ium-4,6-diamine;methyl sulfate Chemical compound COS(O)(=O)=O.COS([O-])(=O)=O.C=1C=C2N(C)C(C)=CC(=N)C2=CC=1NC1=CC(C)=[N+](C)C(N)=N1 WZIPHSLUGLMTRU-UHFFFAOYSA-N 0.000 claims 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims 2
- 229950007857 amicarbalide Drugs 0.000 claims 2
- 238000002512 chemotherapy Methods 0.000 claims 2
- 229940127089 cytotoxic agent Drugs 0.000 claims 2
- 239000002254 cytotoxic agent Substances 0.000 claims 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims 2
- XNYZHCFCZNMTFY-UHFFFAOYSA-N diminazene Chemical compound C1=CC(C(=N)N)=CC=C1N\N=N\C1=CC=C(C(N)=N)C=C1 XNYZHCFCZNMTFY-UHFFFAOYSA-N 0.000 claims 2
- 230000035876 healing Effects 0.000 claims 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims 2
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 claims 2
- 229960001624 pentamidine isethionate Drugs 0.000 claims 2
- YBVNFKZSMZGRAD-UHFFFAOYSA-N pentamidine isethionate Chemical compound OCCS(O)(=O)=O.OCCS(O)(=O)=O.C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 YBVNFKZSMZGRAD-UHFFFAOYSA-N 0.000 claims 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims 2
- 201000002311 trypanosomiasis Diseases 0.000 claims 2
- MOOFYEJFXBSZGE-QJUDHZBZSA-N 1,2-bis[(z)-(4-chlorophenyl)methylideneamino]guanidine Chemical compound C=1C=C(Cl)C=CC=1\C=N/N=C(/N)N\N=C/C1=CC=C(Cl)C=C1 MOOFYEJFXBSZGE-QJUDHZBZSA-N 0.000 claims 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims 1
- 235000001258 Cinchona calisaya Nutrition 0.000 claims 1
- 102100021906 Cyclin-O Human genes 0.000 claims 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 1
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 claims 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
- 229930191564 Monensin Natural products 0.000 claims 1
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 claims 1
- 241000699666 Mus <mouse, genus> Species 0.000 claims 1
- UKHWDRMMMYWSFL-UHFFFAOYSA-N Nicarbazin Chemical compound CC=1C=C(C)NC(=O)N=1.C1=CC([N+](=O)[O-])=CC=C1NC(=O)NC1=CC=C([N+]([O-])=O)C=C1 UKHWDRMMMYWSFL-UHFFFAOYSA-N 0.000 claims 1
- 208000030852 Parasitic disease Diseases 0.000 claims 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims 1
- 229940009456 adriamycin Drugs 0.000 claims 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims 1
- 229960003942 amphotericin b Drugs 0.000 claims 1
- 229960003683 amprolium Drugs 0.000 claims 1
- 239000003972 antineoplastic antibiotic Substances 0.000 claims 1
- 229950003639 buquinolate Drugs 0.000 claims 1
- 229960002092 busulfan Drugs 0.000 claims 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims 1
- 229960004630 chlorambucil Drugs 0.000 claims 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims 1
- 229960002227 clindamycin Drugs 0.000 claims 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims 1
- 229960004397 cyclophosphamide Drugs 0.000 claims 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 1
- 229960000975 daunorubicin Drugs 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 229950007095 diminazene Drugs 0.000 claims 1
- LVVXOXRUTDAKFE-UHFFFAOYSA-N ethyl 6,7-bis(2-methylpropoxy)-4-oxo-1h-quinoline-3-carboxylate Chemical compound CC(C)COC1=C(OCC(C)C)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 LVVXOXRUTDAKFE-UHFFFAOYSA-N 0.000 claims 1
- 229960002949 fluorouracil Drugs 0.000 claims 1
- PJBQYZZKGNOKNJ-UHFFFAOYSA-M hydron;5-[(2-methylpyridin-1-ium-1-yl)methyl]-2-propylpyrimidin-4-amine;dichloride Chemical compound Cl.[Cl-].NC1=NC(CCC)=NC=C1C[N+]1=CC=CC=C1C PJBQYZZKGNOKNJ-UHFFFAOYSA-M 0.000 claims 1
- 108700016226 indium-bleomycin Proteins 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims 1
- 229960004961 mechlorethamine Drugs 0.000 claims 1
- 229960001428 mercaptopurine Drugs 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 229960004023 minocycline Drugs 0.000 claims 1
- 229960005358 monensin Drugs 0.000 claims 1
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 claims 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims 1
- 229960004618 prednisone Drugs 0.000 claims 1
- INDBQLZJXZLFIT-UHFFFAOYSA-N primaquine Chemical compound N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 INDBQLZJXZLFIT-UHFFFAOYSA-N 0.000 claims 1
- 229960005179 primaquine Drugs 0.000 claims 1
- 229960000948 quinine Drugs 0.000 claims 1
- 229960004591 robenidine Drugs 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 229960003087 tioguanine Drugs 0.000 claims 1
- UULSDCUWMKTMND-UHFFFAOYSA-N tryparsamide Chemical compound NC(=O)CNC1=CC=C([As](O)(O)=O)C=C1 UULSDCUWMKTMND-UHFFFAOYSA-N 0.000 claims 1
- 229950000574 tryparsamide Drugs 0.000 claims 1
- 229960003048 vinblastine Drugs 0.000 claims 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims 1
- 229960004528 vincristine Drugs 0.000 claims 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims 1
- 229960004355 vindesine Drugs 0.000 claims 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 claims 1
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 16
- 229920000768 polyamine Polymers 0.000 description 13
- 230000012010 growth Effects 0.000 description 11
- 239000005700 Putrescine Substances 0.000 description 8
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 244000144977 poultry Species 0.000 description 7
- 235000013594 poultry meat Nutrition 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 6
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 6
- 102000004031 Carboxy-Lyases Human genes 0.000 description 5
- 108090000489 Carboxy-Lyases Proteins 0.000 description 5
- 241000271566 Aves Species 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 229940063673 spermidine Drugs 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 3
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 3
- 229960001570 ademetionine Drugs 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 229960003121 arginine Drugs 0.000 description 3
- 229960003104 ornithine Drugs 0.000 description 3
- 229940063675 spermine Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 241000223924 Eimeria Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000606766 Haemophilus parainfluenzae Species 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241001375804 Mastigophora Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 241000223104 Trypanosoma Species 0.000 description 2
- 241000223109 Trypanosoma cruzi Species 0.000 description 2
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229960003646 lysine Drugs 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 125000006308 propyl amino group Chemical group 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- QYPPJABKJHAVHS-UHFFFAOYSA-N Agmatine Natural products NCCCCNC(N)=N QYPPJABKJHAVHS-UHFFFAOYSA-N 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 241000272517 Anseriformes Species 0.000 description 1
- 102000004452 Arginase Human genes 0.000 description 1
- 108700024123 Arginases Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000024699 Chagas disease Diseases 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- 241000193455 Clostridium cadaveris Species 0.000 description 1
- 241000224483 Coccidia Species 0.000 description 1
- 208000003495 Coccidiosis Diseases 0.000 description 1
- 229940123736 Decarboxylase inhibitor Drugs 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000224466 Giardia Species 0.000 description 1
- 241001502121 Glossina brevipalpis Species 0.000 description 1
- 241000948219 Histomonas Species 0.000 description 1
- 241001507061 Isopora Species 0.000 description 1
- 206010023076 Isosporiasis Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- 150000000996 L-ascorbic acids Chemical class 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 102000007357 Methionine adenosyltransferase Human genes 0.000 description 1
- 108010007784 Methionine adenosyltransferase Proteins 0.000 description 1
- 241000282339 Mustela Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010037075 Protozoal infections Diseases 0.000 description 1
- 241000287530 Psittaciformes Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000287231 Serinus Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 241000224526 Trichomonas Species 0.000 description 1
- 241000224557 Trypanosoma brucei brucei Species 0.000 description 1
- 241000223091 Trypanosoma lewisi Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- QYPPJABKJHAVHS-UHFFFAOYSA-P agmatinium(2+) Chemical compound NC(=[NH2+])NCCCC[NH3+] QYPPJABKJHAVHS-UHFFFAOYSA-P 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000003954 decarboxylase inhibitor Substances 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000008262 pumice Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 208000037972 tropical disease Diseases 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
- A23K20/132—Heterocyclic compounds containing only one nitrogen as hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Food Science & Technology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Animal Husbandry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Feed For Specific Animals (AREA)
- Fodder In General (AREA)
Description
1 1941531 194153
Preparaat bestemd voor de profylaxe of behandeling van protozoëninfecties bij dierenPreparation intended for the prophylaxis or treatment of protozoa infections in animals
De uitvinding heeft betrekking op een preparaat dat 2-difluormethyl-2,5-diaminopentaanzuur of een zout of afzonderlijk optisch isomeer daarvan als werkzaam bestanddeel en eventueel een geschikte drager omvat.The invention relates to a composition comprising 2-difluoromethyl-2,5-diaminopentanoic acid or a salt or separate optical isomer thereof as an active ingredient and optionally a suitable carrier.
5 Een dergelijk preparaat wordt beschreven in het Duitse "Offeniegungsschrift” nr. 2.828.739. Hierin wordt eveneens de inhibiterende activiteit van 2-difluormethyl-2,5-diaminopentaanzuur (DFMO) beschreven. Deze activiteit heeft onder andere betrekking op de inhibitie van omithinedecarboxylase waardoor de groei van cellen, alsmede de groei van enkele bacteriën, geïnhibiteerd wordt. In voorbeeld 15 van voomoemd Duits "Offeniegungsschrift” wordt een werkwijze voor de bereiding van DFMO beschreven.Such a preparation is described in German Offeniegungsschrift No. 2,828,739. This also describes the inhibitory activity of 2-difluoromethyl-2,5-diaminopentanoic acid (DFMO). This activity relates inter alia to the inhibition of omithine decarboxylase thereby inhibiting the growth of cells as well as the growth of some bacteria In Example 15 of the aforementioned German "Offeniegungsschrift" a process for the preparation of DFMO is described.
10 Het doel van de uitvinding is om ten behoeve van de profylaxe of behandeling van protozoëninfecties bij dieren een preparaat, zoals omschreven in de aanhef, te verschaffen dat in sterke mate protozoêngroei bij dieren inhibiteertThe object of the invention is to provide for the prophylaxis or treatment of protozoa infections in animals a preparation, as described in the preamble, which strongly inhibits protozoa growth in animals.
Op verrassende wijze werd gevonden dat een preparaat, zoals omschreven in de aanhef, waaraan een synergistisch effectieve hoeveelheid van een tweede werkzaam bestanddeel, te weten Bleomycine, 15 toegevoegd is, in sterke mate protozoêngroei bij dieren inhibiteert.It has been surprisingly found that a preparation, as defined in the preamble, to which a synergistically effective amount of a second active ingredient, namely Bleomycin, has been added, strongly inhibits protozoan growth in animals.
Dienovereenkomstig heeft de uitvinding betrekking op een preparaat, zoals omschreven in de aanhef, daardoor gekenmerkt dat het preparaat verder een synergistisch effectieve hoeveelheid van Bleomycine omvat, en het preparaat bestemd is voor de profylaxe of behandeling van protozoëninfecties bij dieren.Accordingly, the invention relates to a composition as defined in the preamble, characterized in that the composition further comprises a synergistically effective amount of Bleomycin, and the composition is for the prophylaxis or treatment of protozoal infections in animals.
Polyaminen zijn in vele opzichten bij celdeling betrokken. Aangenomen wordt dat storing van de 20 biosynthese van polyaminen door middel van enzyminhibitoren een afneming van de celvermenigvuldiging bij zoogdieren veroorzaakt Hoewel de fysiologische rol van polyaminen niet duidelijk omlijnd is, mag blijkbaar worden verondersteld dat zij betrokken zijn bij celdeling en -groei, H.G. Williams-Ashman et al.,Polyamines are involved in cell division in many ways. Interference with polyamines biosynthesis by enzyme inhibitors is thought to cause a decrease in cell multiplication in mammals. Although the physiological role of polyamines is not clearly defined, they may apparently be implicated in cell division and growth, H.G. Williams-Ashman et al.,
The Italian J. Biochem. 25,5-32 (1976), A. Raina en J. Janne, Med. Biol. 53,121-147 (1975) en D.H. Russell, Life Sciences 13,1635-1647 (1973).The Italian J. Biochem. 25.5-32 (1976), A. Raina and J. Janne, Med. Biol. 53,121-147 (1975) and D.H. Russell, Life Sciences 13.1635-1647 (1973).
25 Polyaminen zijn ook, zoals bekend, essentiële groeifactoren voor bepaalde micro-organismen, bijvoorbeeld voor E. coli, Enterobacter, Klebsiella, Staphylococcus aureus, C. cadaveris, Salmonella typhosa en Haemophilus parainfluenza. Blijkbaar mag worden verondersteld dat polyaminen verbonden zijn aan zowel normale als neoplastische celgroei bij zoogdieren, daar er een toeneming in zowel de synthese als de opzameling van polyaminen plaatsvindt na een celvermenigvuldiging veroorzakende stimulus. Ook is het 30 bekend dat er een correlatie bestaat tussen polyaminevorming en de activiteit van de decarboxylase enzymen van ornithine, S-adenosylmethionine, arginine en lysine. De uitdrukking polyamine wordt geacht het diamine putrescine en de polyaminen spermidine en spermine te omvatten. Putrescine is het product van door omithinedecarboxylase gekatalyseerde decarboxylering van ornithine. Putrescinevorming kan ook optreden door decarboxylering van arginine onder vorming van agmatine dat gehydrolyseerd wordt tot 35 putrescine en ureum. Arginine is ook betrokken bij ornithinevorming door inwerking van het enzym arginase. Activering van methionine door het enzym S-adenosylmethioninesynthetase vormt S-adenosylmethionine dat gedecarboxyleerd wordt. De propylaminerest van het geactiveerde methionine kern daarna naar putrescine worden overgebracht onder vorming van spermidine. Eventueel kan de propylaminerest naar spermidine worden overgebracht onder vorming van spermine. Zodoende dient putrescine als uitgangsstof voor 40 spermidine en spermine. Bovendien is aangetoond dat putrescine een opmerkelijk regelend effect heeft op de biosyntheseweg van polyamine. Ook is aangetoond dat een toenemende putrescinesynthese een vroege indicatie is dat een weefsel hernieuwde groeiprocessen gaat ondergaan. Kadaverine dat het decarboxyfe-ringsproduct van lysine is stimuleert, naar is aangetoond, de activiteit van S-adenosylmethioninede-carboxylase en het is bekend dat het essentieel is voor de groeiprocessen van vele micro-organismen, 45 bijvoorbeeld H. parainfluenza.Polyamines are also known to be essential growth factors for certain microorganisms, for example, for E. coli, Enterobacter, Klebsiella, Staphylococcus aureus, C. cadaveris, Salmonella typhosa and Haemophilus parainfluenza. It can apparently be assumed that polyamines are associated with both normal and neoplastic cell growth in mammals, since there is an increase in both the synthesis and collection of polyamines following a stimulus cell proliferation. It is also known that there is a correlation between polyamine formation and the activity of the decarboxylase enzymes of ornithine, S-adenosylmethionine, arginine and lysine. The term polyamine is meant to include the diamine putrescine and the polyamines spermidine and spermine. Putrescine is the product of omithine decarboxylase catalyzed decarboxylation of ornithine. Putrescine formation can also occur by decarboxylation of arginine to form agmatine which is hydrolyzed to putrescine and urea. Arginine is also involved in ornithine formation by the action of the enzyme arginase. Activation of methionine by the enzyme S-adenosylmethionine synthetase forms S-adenosylmethionine which is decarboxylated. The propylamine residue from the activated methionine core is then transferred to putrescine to form spermidine. Optionally, the propylamine residue can be transferred to spermidine to form spermine. Thus, putrescine serves as the starting material for spermidine and spermine. In addition, putrescine has been shown to have a remarkable regulatory effect on the polyamine biosynthetic pathway. Increased putresin synthesis has also been shown to be an early indication that a tissue is undergoing renewed growth processes. Cadaverine which is the decarboxyphylation product of lysine has been shown to stimulate the activity of S-adenosylmethionine de-carboxylase and it is known to be essential for the growth processes of many microorganisms, for example H. parainfluenza.
De rationale van polyaminemetabolisme is gesuggereerd door Cohen, Science 205,964 (1979). De blijkbaar unieke rol van polyaminemetabolisme in trysanosomen en de afhankelijkheid van trysanosomen van omithinedecarboxylase als putrescinebron, ondersteunt verder de thans gedane waarnemingen dat een bepaalde specifieke omithinedecarboxylase-inhibitor van de polyaminesynthese, te weten DFMO, zeer 50 doeltreffend is voor de inhibitie van protozoêngroei bij dieren.The rationale of polyamine metabolism has been suggested by Cohen, Science 205,964 (1979). The apparently unique role of polyamine metabolism in trysanosomes and the dependence of trysanosomes on omithine decarboxylase as a source of putrescine further supports the current observations that a specific omithine decarboxylase inhibitor of polyamine synthesis, DFMO, is highly effective in inhibiting protozoa. .
DFMO, dat behoort tot een klasse van irreversibele inhibitoren van omithinedecarboxylase, kan worden gebruikt voor de inhibitie van protozoêngroei bij dieren. Deze inhibitie treedt op over een breed spectrum van protozoên, bijvoorbeeld bij leden van het subphylum Sarcomastigophora en Sporozoa. DFMO is bijzonder geschild voor de inhibitie van de groei van leden van de superklasse van Mastigofora, in het 55 bijzonder Trypanosoma brucei brucei en leden van de klasse van Tefospora, in het bijzonder Elmeria tenella, het organisme dat coccidiosis bij pluimvee veroorzaaktDFMO, which belongs to a class of irreversible inhibitors of omithine decarboxylase, can be used to inhibit protozoal growth in animals. This inhibition occurs over a wide spectrum of protozoa, for example in members of the subphylum Sarcomastigophora and Sporozoa. DFMO is particularly peeled for inhibiting the growth of members of the superclass of Mastigofora, in particular Trypanosoma brucei brucei and members of the class of Tefospora, in particular Elmeria tenella, the organism that causes coccidiosis in poultry
Bij toediening in vivo aan dieren met actieve protozoëninfecties, kan men het preparaat volgens de 194153 2 uitvinding gebruiken voor het behandelen van dergelijke dieren door inhibitie van de verdere groei van de protozoêninfecties. Eventueel kan men het preparaat profylactisch toedienen teneinde het opbeden van dergelijke protozoêninfecties te voorkomen.When administered in vivo to animals with active protozoan infections, the composition of the invention can be used to treat such animals by inhibiting further growth of the protozoan infections. Optionally, the composition can be administered prophylactically to prevent the recoiling of such protozoan infections.
In het preparaat volgens de uitvinding kan in plaats van DFMO een zout of afzonderlijk optisch isomeer 5 van DFMO als werkzaam bestanddeel worden gebruikt.In the preparation according to the invention, instead of DFMO, a salt or separate optical isomer of DFMO can be used as the active ingredient.
Goede voorbeelden van de zouten vein DFMO zijn niet-toxische zuuradditiezouten, gevormd met anorganische zuren zoals zoutzuur, broomwaterstofzuur, zwavelzuur of fosforzuur, en organische zuren zoals methaansulfonzuur, salicylzuur, maleïnezuur, malonzuur, wijnsteenzuur, citroenzuur, cyclaamzuur en ascorbinezuur.Good examples of the salts of DFMO are non-toxic acid addition salts formed with inorganic acids such as hydrochloric, hydrobromic, sulfuric or phosphoric, and organic acids such as methanesulfonic, salicylic, maleic, malonic, tartaric, citric, cyclamic and ascorbic acids.
10 Naast de bovengenoemde zouten wordt de uitdrukking "zouten” ook geacht betrekking te hebben op de inwendige zouten van zwitterionen van DFMO dat van amfotere aard is. Hoewel de optische configuratie van het hier toegepaste DFMO niet speciaal wordt aangeduid, heeft het α-koolstofatoom natuurlijk een asymmetrisch centrum en bestaan er bovendien afzonderlijke optische isomeren van DFMO. Aldus kunnen in het preparaat volgens de uitvinding zowel de optische d- en l-isomeren als de racemische mengsels van 15 DFMO worden toegepast.In addition to the aforementioned salts, the term "salts" is also understood to refer to the internal salts of zwitterions of DFMO that are amphoteric in nature. Although the optical configuration of the DFMO used herein is not specifically indicated, the α-carbon atom has an asymmetric center and in addition there are separate optical isomers of DFMO Thus, in the composition of the invention, both the optical d and 1 isomers and the racemic mixtures of DFMO can be used.
De afzonderlijke optische isomeren van DFMO worden gesplitst onder gebruikmaking van een (+) of (-) binaftylfosforzuurzout volgens de werkwijze van R. Viterbo et al., Tetrahedron Letters 48, 4Ö17 (1971). Andere splitsmiddelen zoals (+) kamfer-10-sulfonzuur kunnen ook worden gebruikt. Ook wordt splitsing verkregen via het lactam van DFMO. De afzonderlijke isomeren kunnen op dezelfde wijze worden gebruikt 20 als de racemische mengsels.The individual optical isomers of DFMO are cleaved using a (+) or (-) binaphthyl phosphoric acid salt according to the method of R. Viterbo et al., Tetrahedron Letters 48, 417 (1971). Other splitting agents such as (+) camphor-10-sulfonic acid can also be used. Cleavage is also obtained via the lactam of DFMO. The individual isomers can be used in the same manner as the racemic mixtures.
Het preparaat volgens de uitvinding wordt aldus gebruikt voor het inhibiteren van protozoëngroei bij dieren. De uitdrukking "dieren" heeft hier onder andere betrekking op zoogdieren zoals muizen, ratten, guinese biggetjes, konijnen, fretten, honden, katten, koeien, paarden en primaten met inbegrip van de mens. Onder het begrip "dieren” vallen ook zowel vis als gevogelte. Onder de uitdrukking "gevogelte” worden 25 geacht vogels van allerlei soort en beiderlei geslacht te vallen, met inbegrip van papegaaien en kanaries, maar er wordt vooral pluimvee mee bedoeld dat van commercieel belang is in verband met eieren en vlees. Aldus heeft de uitdrukking "gevogelte" in het bijzonder betrekking op hennen, hanen en woerden van kippen, kalkoenen en eenden.The composition of the invention is thus used to inhibit protozoan growth in animals. The term "animals" refers here, inter alia, to mammals such as mice, rats, guinea pigs, rabbits, ferrets, dogs, cats, cows, horses and primates including humans. The term "animals" includes both fish and poultry. The term "poultry" means 25 birds of all species and of all sexes, including parrots and canaries, but mainly poultry of commercial interest. is related to eggs and meat. Thus, the term "poultry" especially refers to hens, roosters and chickens of chickens, turkeys and ducks.
De uitdrukking "protozoën” wordt geacht de leden te omvatten van de subphyla Sarcomastigophora en 30 Sporozoa van het phylum Protozoa. De hier gebruikte uitdrukking "protozoën” heeft in het bijzonder betrekking op de genera van parasitaire protozoën die voor de mens belangrijk zijn omdat zij ziekten veroorzaken bij de mens of zijn huisdieren. Deze genera worden voor het merendeel ingedeeld bij de superklasse van Mastigophora van het subphylum Sarcomastigophora en de klasse van Telosporea met het subphylum Sporozoa in de indeling volgens Baker (1969). Goede voorbeelden van genera van deze 35 parasitaire protozoën zijn Histomonas, Trypanosoma, Giardia, Trichomonas, Eimeria, Isopora, Toxoplasma en Plasmodium.The term "protozoa" is intended to include members of the subphyla Sarcomastigophora and 30 Sporozoa of the phylum Protozoa. The term "protozoa" used herein refers in particular to the genera of parasitic protozoa that are important to humans because they are diseases in humans or pets. These genera are mainly classified in the superclass of Mastigophora of the subphylum Sarcomastigophora and the class of Telosporea with the subphylum Sporozoa in the classification according to Baker (1969). Good examples of genera of these 35 parasitic protozoa are Histomonas, Trypanosoma, Giardia, Trichomonas, Eimeria, Isopora, Toxoplasma and Plasmodium.
Uitgesloten van de superklasse van Mastigophora is het genus Leishmania waarvan bepaalde species de tropische ziekte Leishmaniasis bij de mens veroorzaken. Ook met name uitgesloten van het genus Trypanosoma, zoals hier wordt bedoeld, zijn de species Trypanosoma cruzi, die bij de mens de ziekte van 40 Chagas veroorzaken en de species Trypanosoma lewisi. DFMO is tegen deze species niet bijzonder doeltreffend gebleken.Excluded from the superclass of Mastigophora is the genus Leishmania, of which certain species cause the tropical disease Leishmaniasis in humans. Also notably excluded from the genus Trypanosoma, as referred to herein, are the species Trypanosoma cruzi, which cause Chagas disease in humans and the species Trypanosoma lewisi. DFMO has not been shown to be particularly effective against these species.
Anderzijds kan men het preparaat bijzonder goed gebruiken voor het inhibiteren van de groei van Trypanosoma brucei, de verwekker van nagana ofwel de tsetse-vliegziekte bij paarden en hoornvee in Centraal Afrika. Het onderhavige preparaat is ook opmerkelijk doeltreffend bij de inhibitie van Eimeria 45 teneiia, een protozoënspecies dat coocidiosis veroorzaakt bij vogels.On the other hand, the preparation can be used particularly well to inhibit the growth of Trypanosoma brucei, the causative agent of nagana or the tsetse fly sickness in horses and horned cattle in Central Africa. The present composition is also remarkably effective in inhibiting Eimeria 45 teneiia, a protozoan species that causes coocidiosis in birds.
Het preparaat kan ook gebruikt worden ter inhibitie van de groei van intestinale coccidia bij commercieel pluimvee.The preparation can also be used to inhibit the growth of intestinal coccidia in commercial poultry.
Het farmaceutische preparaat volgens de uitvinding, dat bijzonder geschikt is voor de profylaxe of behandeling van protozoêninfecties bij gevogelte, kan naast DFMO en Blesmycine als werkzame bestand-50 delen, een farmaceutisch aanvaardbare drager omvatten. Men kan de antiprotozoênpreparaten goed bereiden door de werkzame bestanddelen met een inerte drager te vermengen. Goede voorbeelden van dragers zijn talk, klei, puimsteen, siliciumoxide, kalk, diatomeeênaarde, notedoppenbloem en equivalenten daarvan. Eventueel kunnen de werkzame bestanddelen vermengd worden met een in de handel verkrijgbare poeder of vitaminen en mineralen bijmengsel dat bijzonder geschikt is voor vogels.The pharmaceutical composition of the invention, which is particularly suitable for the prophylaxis or treatment of poultry protozoan infections, may comprise, in addition to DFMO and Blesmycin as active ingredients, a pharmaceutically acceptable carrier. The antiprotozoal preparations can be well prepared by mixing the active ingredients with an inert carrier. Good examples of carriers are talc, clay, pumice, silicon oxide, lime, diatomaceous earth, nutshell flour and equivalents thereof. Optionally, the active ingredients may be mixed with a commercially available powder or vitamin and mineral admixture which is particularly suitable for birds.
55 In de meeste gevallen gebruikt men een geconcentreerde oplossing van de werkzame bestanddelen in water bij de hantering en behandeling van cocddiosis bij vogels.55 In most cases, a concentrated solution of the active ingredients in water is used in the handling and treatment of cocddiosis in birds.
Het preparaat volgens de uitvinding kan in combinatie worden gebruikt met andere bekende geneesmid-The preparation according to the invention can be used in combination with other known medicaments
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15997380A | 1980-06-16 | 1980-06-16 | |
| US15997380 | 1980-06-16 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NL8102863A NL8102863A (en) | 1982-01-18 |
| NL194153B NL194153B (en) | 2001-04-02 |
| NL194153C true NL194153C (en) | 2001-08-03 |
Family
ID=22574910
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NL8102863A NL194153C (en) | 1980-06-16 | 1981-06-15 | Preparation intended for the prophylaxis or treatment of protozoan infections in animals. |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS5731613A (en) |
| AT (1) | AT377180B (en) |
| AU (1) | AU544990B2 (en) |
| BE (1) | BE889230A (en) |
| CA (1) | CA1174603A (en) |
| CH (1) | CH651206A5 (en) |
| DE (2) | DE3123295A1 (en) |
| FR (1) | FR2484255A1 (en) |
| GB (1) | GB2078735B (en) |
| IE (1) | IE51300B1 (en) |
| IL (1) | IL63087A (en) |
| IT (1) | IT1171380B (en) |
| NL (1) | NL194153C (en) |
| NZ (1) | NZ197394A (en) |
| PH (1) | PH16634A (en) |
| SE (1) | SE460517B (en) |
| ZA (1) | ZA813953B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58123555U (en) * | 1982-02-17 | 1983-08-23 | 三菱電機株式会社 | In-line electron gun assembly equipment |
| NL8400927A (en) * | 1984-03-23 | 1985-10-16 | Philips Nv | DEVICE AND METHOD FOR MOUNTING AN INTEGRATED ELECTRON CANNON SYSTEM. |
| DE3421384A1 (en) * | 1984-06-08 | 1985-12-12 | Standard Elektrik Lorenz Ag, 7000 Stuttgart | DEVICE FOR ASSEMBLING ELECTRONIC RADIATOR GENERATORS |
| JPS62148462A (en) * | 1985-12-19 | 1987-07-02 | メレルダウフア−マス−テイカルズ インコ−ポレ−テツド | Novel method of controlling growth of protozoa |
| ATE77367T1 (en) * | 1988-02-05 | 1992-07-15 | Merrell Dow Pharma | 5-SUBSTITUTED ORNITHINE DERIVATIVES. |
| US5455234A (en) * | 1994-03-16 | 1995-10-03 | Ahluwalia; Gurpreet S. | Inhibition of hair growth |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ187377A (en) * | 1977-06-01 | 1981-05-15 | Merck & Co Inc | A-amino-a-substituted alkyl-a-fluoromethylacetic acids |
| US4139563A (en) * | 1977-07-01 | 1979-02-13 | Merrell Toraude Et Compagnie | α-ACETYLENIC DERIVATIVES OF AMINES |
| US4182891A (en) * | 1977-07-01 | 1980-01-08 | Merrell Toraude Et Compagnie | α-Acetylenic derivatives of α-amino acids |
| US4088667A (en) * | 1977-07-01 | 1978-05-09 | Merrell Toraude Et Compagnie | Lower alkyl 2-tri-(lower)alkylsilylacetylene-N-carbethoxyglycinates and process for using same |
| CA1121375A (en) * | 1977-07-01 | 1982-04-06 | Brian W. Metcalf | Derivatives of amines and amino acids |
| CA1091661A (en) | 1977-07-11 | 1980-12-16 | Philippe Bey | .alpha.-HALOMETHYL DERIVATIVES OF .alpha.-AMINO ACIDS |
| US4134918A (en) * | 1977-09-06 | 1979-01-16 | Merrell Toraude Et Compagnie | Alpha-halomethyl derivatives of amines |
-
1981
- 1981-06-11 CA CA000379588A patent/CA1174603A/en not_active Expired
- 1981-06-11 SE SE8103678A patent/SE460517B/en not_active IP Right Cessation
- 1981-06-11 PH PH25759A patent/PH16634A/en unknown
- 1981-06-11 AU AU71654/81A patent/AU544990B2/en not_active Expired
- 1981-06-11 NZ NZ197394A patent/NZ197394A/en unknown
- 1981-06-11 ZA ZA813953A patent/ZA813953B/en unknown
- 1981-06-12 DE DE19813123295 patent/DE3123295A1/en active Granted
- 1981-06-12 DE DE3153623A patent/DE3153623C2/de not_active Expired - Lifetime
- 1981-06-12 IE IE1308/81A patent/IE51300B1/en not_active IP Right Cessation
- 1981-06-12 IL IL63087A patent/IL63087A/en not_active IP Right Cessation
- 1981-06-15 JP JP9208181A patent/JPS5731613A/en active Granted
- 1981-06-15 IT IT48684/81A patent/IT1171380B/en active
- 1981-06-15 FR FR8111733A patent/FR2484255A1/en active Granted
- 1981-06-15 AT AT0266581A patent/AT377180B/en not_active IP Right Cessation
- 1981-06-15 GB GB8118326A patent/GB2078735B/en not_active Expired
- 1981-06-15 BE BE0/205104A patent/BE889230A/en not_active IP Right Cessation
- 1981-06-15 CH CH3939/81A patent/CH651206A5/en not_active IP Right Cessation
- 1981-06-15 NL NL8102863A patent/NL194153C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PH16634A (en) | 1983-12-05 |
| IL63087A (en) | 1984-10-31 |
| JPS5731613A (en) | 1982-02-20 |
| GB2078735A (en) | 1982-01-13 |
| CA1174603A (en) | 1984-09-18 |
| FR2484255B1 (en) | 1984-12-14 |
| IT1171380B (en) | 1987-06-10 |
| IT8148684A0 (en) | 1981-06-15 |
| FR2484255A1 (en) | 1981-12-18 |
| CH651206A5 (en) | 1985-09-13 |
| GB2078735B (en) | 1985-05-15 |
| BE889230A (en) | 1981-12-15 |
| DE3123295A1 (en) | 1982-04-29 |
| DE3123295C2 (en) | 1990-07-12 |
| IE51300B1 (en) | 1986-11-26 |
| ZA813953B (en) | 1982-06-30 |
| NL194153B (en) | 2001-04-02 |
| AT377180B (en) | 1985-02-25 |
| AU544990B2 (en) | 1985-06-27 |
| AU7165481A (en) | 1981-12-24 |
| NZ197394A (en) | 1984-09-28 |
| SE8103678L (en) | 1981-12-17 |
| NL8102863A (en) | 1982-01-18 |
| JPH0432052B2 (en) | 1992-05-28 |
| DE3153623C2 (en) | 1991-06-27 |
| SE460517B (en) | 1989-10-23 |
| IE811308L (en) | 1981-12-16 |
| ATA266581A (en) | 1984-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4399151A (en) | Method of inhibiting the growth of protozoa | |
| US6166086A (en) | Small molecules that increase the conversion of food to body weight gain | |
| US20150258047A1 (en) | Therapeutic Compounds | |
| US20200268686A1 (en) | Sphingoid compounds for prophylaxis and/or therapy of a viral infection | |
| US20060122144A1 (en) | Compounds resistant to metabolic deactivation and methods of use | |
| US10813914B2 (en) | Composition for controlling microsporidia in fishes and method for controlling microsporidia in fishes using same | |
| NL194153C (en) | Preparation intended for the prophylaxis or treatment of protozoan infections in animals. | |
| US20170007562A1 (en) | Use of Guanidinoacetic Acid and/or Creatine for Increasing the Hatch Rate | |
| Kawano et al. | Antiparasitic effect of in-feed inhibitors of folic acid synthesis and dihydrofolate reductase against ciliate Cryptocaryon irritans infection in the red sea bream Pagrus major and against ciliate Ichthyophthirius multifiliis infection in black pop-eyed goldfish Carassius auratus | |
| Ali | Some pharmacological and toxicological properties of furazolidone | |
| US20060142251A1 (en) | Anti-microbial agents derived from methionine sulfoximine analogues | |
| RU2473334C2 (en) | Anti-eimeriosis pharmaceutical composition based on salt of quarternary phosphonium and substituted dinitrobenzofuroxane | |
| Stabler et al. | Effect of 2-amino-5-nitrothiazole (enheptin) and other drugs on Trichomonas gallinae infection in the domestic pigeon | |
| RU2502511C1 (en) | Agent for treating coccidiosis in veterinary science | |
| KR100821112B1 (en) | Praziquantel compounds for treating diseases due to sarcosystis, neospora, toxoplasma and isospora | |
| Freed et al. | Production of convulsions in mice by the combination of methionine and homocysteine | |
| Mitchell | Ponazuril | |
| RU2418579C1 (en) | Immunostimulating medication for selenium exchange normalisation and correction of stress states for agricultural animals | |
| EP3429563B1 (en) | Desformylflustrabromine for use in the treatment of obsessive-compulsive and related disorders | |
| RU2322235C1 (en) | Method for preventing and treating eimeriosis in animals and poultry | |
| JP2022542691A (en) | Veterinary composition for the prevention and/or treatment of cryptosporidiosis | |
| RU2354353C1 (en) | Preparation for treatment of colibacillosis in young agricultural animals | |
| RU2659937C1 (en) | Method for treatment and group prophylaxis of gastrointestinal cestodiasis and nematodosis of sheep | |
| RU2639133C1 (en) | Antiparastic means for pigs eimeriosis treatment and prevention | |
| RU2505285C1 (en) | Method for increasing biocidal and therapeutic action of suspension-cream with linco-spectin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A85 | Still pending on 85-01-01 | ||
| BA | A request for search or an international-type search has been filed | ||
| BB | A search report has been drawn up | ||
| BC | A request for examination has been filed | ||
| DNT | Communications of changes of names of applicants whose applications have been laid open to public inspection |
Free format text: MERRELL PHARMACEUTICALS INC. |
|
| V4 | Discontinued because of reaching the maximum lifetime of a patent |
Free format text: 20010803 |