CN101686962A - 驱虫药联合用药 - Google Patents
驱虫药联合用药 Download PDFInfo
- Publication number
- CN101686962A CN101686962A CN200880022643A CN200880022643A CN101686962A CN 101686962 A CN101686962 A CN 101686962A CN 200880022643 A CN200880022643 A CN 200880022643A CN 200880022643 A CN200880022643 A CN 200880022643A CN 101686962 A CN101686962 A CN 101686962A
- Authority
- CN
- China
- Prior art keywords
- abamectin
- desoxoparaherquamide
- mammal
- treatment
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000000507 anthelmentic effect Effects 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 239000005660 Abamectin Substances 0.000 claims abstract description 26
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 claims abstract description 25
- 229950008167 abamectin Drugs 0.000 claims abstract description 24
- 241000124008 Mammalia Species 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 19
- 241001494479 Pecora Species 0.000 claims description 16
- 244000045947 parasite Species 0.000 claims description 16
- 208000030852 Parasitic disease Diseases 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 6
- 241000244206 Nematoda Species 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 12
- 230000003071 parasitic effect Effects 0.000 abstract description 7
- 206010061217 Infestation Diseases 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 33
- 239000003826 tablet Substances 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000007788 liquid Substances 0.000 description 15
- 239000002552 dosage form Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 230000003213 activating effect Effects 0.000 description 9
- 230000037396 body weight Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000255925 Diptera Species 0.000 description 6
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003674 animal food additive Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000000890 drug combination Substances 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 229960001614 levamisole Drugs 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 230000002421 anti-septic effect Effects 0.000 description 5
- 235000010603 pastilles Nutrition 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 210000000582 semen Anatomy 0.000 description 5
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 4
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 4
- 241000238421 Arthropoda Species 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241001467800 Knemidokoptes Species 0.000 description 4
- 241000243789 Metastrongyloidea Species 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 241000347415 Teladorsagia Species 0.000 description 4
- 241000191771 Teladorsagia circumcincta Species 0.000 description 4
- 229960002669 albendazole Drugs 0.000 description 4
- HXHWSAZORRCQMX-UHFFFAOYSA-N albendazole Chemical compound CCCSC1=CC=C2NC(NC(=O)OC)=NC2=C1 HXHWSAZORRCQMX-UHFFFAOYSA-N 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000003304 gavage Methods 0.000 description 4
- 239000001087 glyceryl triacetate Substances 0.000 description 4
- 235000013773 glyceryl triacetate Nutrition 0.000 description 4
- 229960002418 ivermectin Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000002906 microbiologic effect Effects 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229960002622 triacetin Drugs 0.000 description 4
- 241000238876 Acari Species 0.000 description 3
- 241000238682 Amblyomma americanum Species 0.000 description 3
- 241001480737 Amblyomma maculatum Species 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 3
- 241001327638 Cimex lectularius Species 0.000 description 3
- 241001480793 Dermacentor variabilis Species 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- 241000283073 Equus caballus Species 0.000 description 3
- 241000257232 Haematobia irritans Species 0.000 description 3
- 241000670091 Haematopinus suis Species 0.000 description 3
- 241000243974 Haemonchus contortus Species 0.000 description 3
- 241000771994 Melophagus ovinus Species 0.000 description 3
- 241000243795 Ostertagia Species 0.000 description 3
- 241001480756 Otobius megnini Species 0.000 description 3
- 241000238680 Rhipicephalus microplus Species 0.000 description 3
- 241001481696 Rhipicephalus sanguineus Species 0.000 description 3
- 241000509427 Sarcoptes scabiei Species 0.000 description 3
- 241000243797 Trichostrongylus Species 0.000 description 3
- 241000243796 Trichostrongylus colubriformis Species 0.000 description 3
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 3
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002550 fecal effect Effects 0.000 description 3
- -1 glyceroformol Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000003120 macrolide antibiotic agent Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000004681 ovum Anatomy 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 241000256111 Aedes <genus> Species 0.000 description 2
- 241000243791 Angiostrongylus Species 0.000 description 2
- 241000244023 Anisakis Species 0.000 description 2
- 241000256186 Anopheles <genus> Species 0.000 description 2
- 241000790794 Argulus Species 0.000 description 2
- 241000244186 Ascaris Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241001113967 Bovicola ovis Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000893172 Chabertia Species 0.000 description 2
- 241000256135 Chironomus thummi Species 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 241001126268 Cooperia Species 0.000 description 2
- 241000256054 Culex <genus> Species 0.000 description 2
- 241000732108 Culiseta Species 0.000 description 2
- 241001128004 Demodex Species 0.000 description 2
- 241001128002 Demodex canis Species 0.000 description 2
- 241001481695 Dermanyssus gallinae Species 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
- 241001147667 Dictyocaulus Species 0.000 description 2
- 241000243990 Dirofilaria Species 0.000 description 2
- 235000003550 Dracunculus Nutrition 0.000 description 2
- 241000316827 Dracunculus <angiosperm> Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000239183 Filaria Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 241001660201 Gasterophilus intestinalis Species 0.000 description 2
- 241001194754 Gasterophilus nasalis Species 0.000 description 2
- 241000790933 Haematopinus Species 0.000 description 2
- 241000894055 Haematopinus eurysternus Species 0.000 description 2
- 241000243976 Haemonchus Species 0.000 description 2
- 241000500891 Insecta Species 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000257162 Lucilia <blowfly> Species 0.000 description 2
- 241000920471 Lucilia caesar Species 0.000 description 2
- 241000556230 Metastrongylus Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000986227 Muellerius Species 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 241000498270 Necator americanus Species 0.000 description 2
- 241001137882 Nematodirus Species 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 241000510960 Oesophagostomum Species 0.000 description 2
- 241000543819 Oestrus ovis Species 0.000 description 2
- 241000243981 Onchocerca Species 0.000 description 2
- 241000517307 Pediculus humanus Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 241001617421 Protostrongylus Species 0.000 description 2
- 241001649229 Psoroptes Species 0.000 description 2
- 235000005775 Setaria Nutrition 0.000 description 2
- 241000232088 Setaria <nematode> Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 241000607216 Toxascaris Species 0.000 description 2
- 241000242541 Trematoda Species 0.000 description 2
- 241000243774 Trichinella Species 0.000 description 2
- 241000244005 Wuchereria bancrofti Species 0.000 description 2
- 210000003165 abomasum Anatomy 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000002141 anti-parasite Effects 0.000 description 2
- 239000003096 antiparasitic agent Substances 0.000 description 2
- 238000011888 autopsy Methods 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
- 229940038472 dicalcium phosphate Drugs 0.000 description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
- 238000007908 dry granulation Methods 0.000 description 2
- 239000013057 ectoparasiticide Substances 0.000 description 2
- 244000079386 endoparasite Species 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000003664 filaricide agent Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 244000000050 gastrointestinal parasite Species 0.000 description 2
- 239000008240 homogeneous mixture Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000006201 parenteral dosage form Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- MTXSIJUGVMTTMU-JTQLQIEISA-N (S)-anabasine Chemical compound N1CCCC[C@H]1C1=CC=CN=C1 MTXSIJUGVMTTMU-JTQLQIEISA-N 0.000 description 1
- LAOOXBLMIJHMFO-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-methylthioxanthen-9-one;hydron;chloride Chemical compound Cl.S1C2=CC=CC=C2C(=O)C2=C1C(C)=CC=C2NCCN(CC)CC LAOOXBLMIJHMFO-UHFFFAOYSA-N 0.000 description 1
- NVEPPWDVLBMNMB-SNAWJCMRSA-N 1-methyl-2-[(e)-2-(3-methylthiophen-2-yl)ethenyl]-5,6-dihydro-4h-pyrimidine Chemical compound CN1CCCN=C1\C=C\C1=C(C)C=CS1 NVEPPWDVLBMNMB-SNAWJCMRSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- RFEJUZJILGIRHQ-XRIOVQLTSA-N 2,3-dihydroxybutanedioic acid;3-[(2s)-1-methylpyrrolidin-2-yl]pyridine Chemical compound OC(=O)C(O)C(O)C(O)=O.OC(=O)C(O)C(O)C(O)=O.CN1CCC[C@H]1C1=CC=CN=C1 RFEJUZJILGIRHQ-XRIOVQLTSA-N 0.000 description 1
- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 description 1
- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 description 1
- UMZCLZPXPCNKML-UHFFFAOYSA-N 2h-imidazo[4,5-d][1,3]thiazole Chemical class C1=NC2=NCSC2=N1 UMZCLZPXPCNKML-UHFFFAOYSA-N 0.000 description 1
- QOVTVIYTBRHADL-UHFFFAOYSA-N 4-amino-6-(1,2,2-trichloroethenyl)benzene-1,3-disulfonamide Chemical compound NC1=CC(C(Cl)=C(Cl)Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O QOVTVIYTBRHADL-UHFFFAOYSA-N 0.000 description 1
- 241000244044 Acanthocheilonema Species 0.000 description 1
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241001147657 Ancylostoma Species 0.000 description 1
- 241000239223 Arachnida Species 0.000 description 1
- 241001480752 Argas persicus Species 0.000 description 1
- 241000322476 Bovicola bovis Species 0.000 description 1
- 241000244036 Brugia Species 0.000 description 1
- 241000931178 Bunostomum Species 0.000 description 1
- 241000931177 Bunostomum trigonocephalum Species 0.000 description 1
- JFLRKDZMHNBDQS-UCQUSYKYSA-N CC[C@H]1CCC[C@@H]([C@H](C(=O)C2=C[C@H]3[C@@H]4C[C@@H](C[C@H]4C(=C[C@H]3[C@@H]2CC(=O)O1)C)O[C@H]5[C@@H]([C@@H]([C@H]([C@@H](O5)C)OC)OC)OC)C)O[C@H]6CC[C@@H]([C@H](O6)C)N(C)C.CC[C@H]1CCC[C@@H]([C@H](C(=O)C2=C[C@H]3[C@@H]4C[C@@H](C[C@H]4C=C[C@H]3C2CC(=O)O1)O[C@H]5[C@@H]([C@@H]([C@H]([C@@H](O5)C)OC)OC)OC)C)O[C@H]6CC[C@@H]([C@H](O6)C)N(C)C Chemical compound CC[C@H]1CCC[C@@H]([C@H](C(=O)C2=C[C@H]3[C@@H]4C[C@@H](C[C@H]4C(=C[C@H]3[C@@H]2CC(=O)O1)C)O[C@H]5[C@@H]([C@@H]([C@H]([C@@H](O5)C)OC)OC)OC)C)O[C@H]6CC[C@@H]([C@H](O6)C)N(C)C.CC[C@H]1CCC[C@@H]([C@H](C(=O)C2=C[C@H]3[C@@H]4C[C@@H](C[C@H]4C=C[C@H]3C2CC(=O)O1)O[C@H]5[C@@H]([C@@H]([C@H]([C@@H](O5)C)OC)OC)OC)C)O[C@H]6CC[C@@H]([C@H](O6)C)N(C)C JFLRKDZMHNBDQS-UCQUSYKYSA-N 0.000 description 1
- 241001611011 Caligus Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000134426 Ceratopogonidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 241000242722 Cestoda Species 0.000 description 1
- 241001124179 Chrysops Species 0.000 description 1
- 208000003495 Coccidiosis Diseases 0.000 description 1
- 241000202814 Cochliomyia hominivorax Species 0.000 description 1
- 101800004637 Communis Proteins 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 241000134316 Culicoides <genus> Species 0.000 description 1
- 241000522489 Cyathostomum Species 0.000 description 1
- 241000520249 Cylicocyclus Species 0.000 description 1
- 241000193880 Demodex folliculorum Species 0.000 description 1
- 241001127981 Demodicidae Species 0.000 description 1
- 108010002156 Depsipeptides Proteins 0.000 description 1
- 241001480819 Dermacentor andersoni Species 0.000 description 1
- 241000202828 Dermatobia hominis Species 0.000 description 1
- 241000189163 Dipetalonema Species 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 241000223924 Eimeria Species 0.000 description 1
- 241001069183 Elaeophora Species 0.000 description 1
- 206010014979 Epidemic typhus Diseases 0.000 description 1
- 241000958182 Fannia scalaris Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000692264 Gasterophilus haemorrhoidalis Species 0.000 description 1
- 241000257324 Glossina <genus> Species 0.000 description 1
- 241001502121 Glossina brevipalpis Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000875835 Haematopinus asini Species 0.000 description 1
- 206010061201 Helminthic infection Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000562421 Hydrotaea irritans Species 0.000 description 1
- 241000543830 Hypoderma bovis Species 0.000 description 1
- 241000257174 Hypoderma lineatum Species 0.000 description 1
- 206010023076 Isosporiasis Diseases 0.000 description 1
- 241001480843 Ixodes ricinus Species 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 241000670112 Linognathus ovillus Species 0.000 description 1
- 244000309753 Linognathus pedalis Species 0.000 description 1
- 241001113946 Linognathus vituli Species 0.000 description 1
- 239000005912 Lufenuron Substances 0.000 description 1
- 229930188848 Marcfortine Natural products 0.000 description 1
- YRWLZFXJFBZBEY-UHFFFAOYSA-N N-(6-butyl-1H-benzimidazol-2-yl)carbamic acid methyl ester Chemical compound CCCCC1=CC=C2N=C(NC(=O)OC)NC2=C1 YRWLZFXJFBZBEY-UHFFFAOYSA-N 0.000 description 1
- RAOCRURYZCVHMG-UHFFFAOYSA-N N-(6-propoxy-1H-benzimidazol-2-yl)carbamic acid methyl ester Chemical compound CCCOC1=CC=C2N=C(NC(=O)OC)NC2=C1 RAOCRURYZCVHMG-UHFFFAOYSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- JMPFSEBWVLAJKM-UHFFFAOYSA-N N-{5-chloro-4-[(4-chlorophenyl)(cyano)methyl]-2-methylphenyl}-2-hydroxy-3,5-diiodobenzamide Chemical compound ClC=1C=C(NC(=O)C=2C(=C(I)C=C(I)C=2)O)C(C)=CC=1C(C#N)C1=CC=C(Cl)C=C1 JMPFSEBWVLAJKM-UHFFFAOYSA-N 0.000 description 1
- 241000243985 Onchocerca volvulus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000244187 Parascaris Species 0.000 description 1
- 241000257186 Phormia regina Species 0.000 description 1
- 241001474791 Proboscis Species 0.000 description 1
- 241001649230 Psoroptes ovis Species 0.000 description 1
- AQXXZDYPVDOQEE-MXDQRGINSA-N Pyrantel pamoate Chemical compound CN1CCCN=C1\C=C\C1=CC=CS1.C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 AQXXZDYPVDOQEE-MXDQRGINSA-N 0.000 description 1
- 241000044147 Solenopotes capillatus Species 0.000 description 1
- 239000005930 Spinosad Substances 0.000 description 1
- 206010059343 Stenocephaly Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 241001220316 Syngamus Species 0.000 description 1
- 241001481659 Syrphidae Species 0.000 description 1
- 241000255632 Tabanus atratus Species 0.000 description 1
- 241000244031 Toxocara Species 0.000 description 1
- 241000197881 Trichocephalus Species 0.000 description 1
- 241001489151 Trichuris Species 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 241000571980 Uncinaria stenocephala Species 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 241000282487 Vulpes Species 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- 229930014345 anabasine Natural products 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229960003475 cambendazole Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229960000275 clorsulon Drugs 0.000 description 1
- 229950004178 closantel Drugs 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 108010056417 emodepside Proteins 0.000 description 1
- ZMQMTKVVAMWKNY-YSXLEBCMSA-N emodepside Chemical compound C([C@@H]1C(=O)N(C)[C@@H](CC(C)C)C(=O)O[C@H](C)C(=O)N(C)[C@H](C(O[C@H](CC=2C=CC(=CC=2)N2CCOCC2)C(=O)N(C)[C@@H](CC(C)C)C(=O)O[C@H](C)C(=O)N(C)[C@@H](CC(C)C)C(=O)O1)=O)CC(C)C)C(C=C1)=CC=C1N1CCOCC1 ZMQMTKVVAMWKNY-YSXLEBCMSA-N 0.000 description 1
- 229960001575 emodepside Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229960005473 fenbendazole Drugs 0.000 description 1
- IRHZVMHXVHSMKB-UHFFFAOYSA-N fenbendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1SC1=CC=CC=C1 IRHZVMHXVHSMKB-UHFFFAOYSA-N 0.000 description 1
- 229960004500 flubendazole Drugs 0.000 description 1
- CPEUVMUXAHMANV-UHFFFAOYSA-N flubendazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=C(F)C=C1 CPEUVMUXAHMANV-UHFFFAOYSA-N 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 201000006592 giardiasis Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 229960000521 lufenuron Drugs 0.000 description 1
- PWPJGUXAGUPAHP-UHFFFAOYSA-N lufenuron Chemical compound C1=C(Cl)C(OC(F)(F)C(C(F)(F)F)F)=CC(Cl)=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F PWPJGUXAGUPAHP-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003439 mebendazole Drugs 0.000 description 1
- BAXLBXFAUKGCDY-UHFFFAOYSA-N mebendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CC=C1 BAXLBXFAUKGCDY-UHFFFAOYSA-N 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960001952 metrifonate Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- FXWHFKOXMBTCMP-WMEDONTMSA-N milbemycin Natural products COC1C2OCC3=C/C=C/C(C)CC(=CCC4CC(CC5(O4)OC(C)C(C)C(OC(=O)C(C)CC(C)C)C5O)OC(=O)C(C=C1C)C23O)C FXWHFKOXMBTCMP-WMEDONTMSA-N 0.000 description 1
- 201000002266 mite infestation Diseases 0.000 description 1
- 229960005121 morantel Drugs 0.000 description 1
- MENOBBYDZHOWLE-UHFFFAOYSA-N morpholine-2,3-dione Chemical compound O=C1NCCOC1=O MENOBBYDZHOWLE-UHFFFAOYSA-N 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- QNSIFYWAPWSAIJ-UHFFFAOYSA-N naftalofos Chemical compound C1=CC(C(N(OP(=O)(OCC)OCC)C2=O)=O)=C3C2=CC=CC3=C1 QNSIFYWAPWSAIJ-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000005645 nematicide Substances 0.000 description 1
- 229960001920 niclosamide Drugs 0.000 description 1
- RJMUSRYZPJIFPJ-UHFFFAOYSA-N niclosamide Chemical compound OC1=CC=C(Cl)C=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1Cl RJMUSRYZPJIFPJ-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- SVMGVZLUIWGYPH-UHFFFAOYSA-N nitroscanate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C(N=C=S)C=C1 SVMGVZLUIWGYPH-UHFFFAOYSA-N 0.000 description 1
- 229950009909 nitroscanate Drugs 0.000 description 1
- 208000002042 onchocerciasis Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960000535 oxantel Drugs 0.000 description 1
- VRYKTHBAWRESFI-VOTSOKGWSA-N oxantel Chemical compound CN1CCCN=C1\C=C\C1=CC=CC(O)=C1 VRYKTHBAWRESFI-VOTSOKGWSA-N 0.000 description 1
- 229960004454 oxfendazole Drugs 0.000 description 1
- BEZZFPOZAYTVHN-UHFFFAOYSA-N oxfendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1S(=O)C1=CC=CC=C1 BEZZFPOZAYTVHN-UHFFFAOYSA-N 0.000 description 1
- 229960002762 oxibendazole Drugs 0.000 description 1
- 229930188716 paraherquamide Natural products 0.000 description 1
- UVZZDDLIOJPDKX-ITKQZBBDSA-N paraherquamide Chemical compound O1C(C)(C)C=COC2=C1C=CC1=C2NC(=O)[C@]11C(C)(C)[C@@H]2C[C@]3(N(C4)CC[C@@]3(C)O)C(=O)N(C)[C@]42C1 UVZZDDLIOJPDKX-ITKQZBBDSA-N 0.000 description 1
- UVZZDDLIOJPDKX-UHFFFAOYSA-N paraherquamide A Natural products O1C(C)(C)C=COC2=C1C=CC1=C2NC(=O)C11C(C)(C)C2CC3(N(C4)CCC3(C)O)C(=O)N(C)C42C1 UVZZDDLIOJPDKX-UHFFFAOYSA-N 0.000 description 1
- 230000000590 parasiticidal effect Effects 0.000 description 1
- 239000002297 parasiticide Substances 0.000 description 1
- 229950007337 parbendazole Drugs 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000004540 pour-on Substances 0.000 description 1
- 229960002957 praziquantel Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- QZWHWHNCPFEXLL-UHFFFAOYSA-N propan-2-yl n-[2-(1,3-thiazol-4-yl)-3h-benzimidazol-5-yl]carbamate Chemical compound N1C2=CC(NC(=O)OC(C)C)=CC=C2N=C1C1=CSC=N1 QZWHWHNCPFEXLL-UHFFFAOYSA-N 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960000996 pyrantel pamoate Drugs 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical class O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- WKEDVNSFRWHDNR-UHFFFAOYSA-N salicylanilide Chemical compound OC1=CC=CC=C1C(=O)NC1=CC=CC=C1 WKEDVNSFRWHDNR-UHFFFAOYSA-N 0.000 description 1
- 229950000975 salicylanilide Drugs 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 230000001843 schistosomicidal effect Effects 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229940014213 spinosad Drugs 0.000 description 1
- 239000004544 spot-on Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005326 tetrahydropyrimidines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- 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
- A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
提供了治疗哺乳动物寄生虫感染的方法，包括同时或依次对该哺乳动物给予有效量的(a)2－desoxoparaherquamide；和(b)阿巴克丁的步骤。还提供了包含2－desoxoparaherquamide和阿巴克丁的驱虫组合物。
Description
本发明涉及使用2-desoxoparaherquamide和阿巴克丁的联合用药治疗寄生虫感染，特别是蠕虫感染的方法，和包含这些药物作为活性组分的新的驱虫组合物。
发明背景
控制人体和动物群体中的寄生虫感染仍然是全世界重要的努力方向。可以将致病性生物体分类为线虫纲(Nematoda)，绦虫纲(Cestoidea)和吸虫纲(Trematoda)或原生动物门(phylum Protozoa)类别的体内寄生虫的成员或节肢动物门(phylum Arthropoda)的体外寄生虫的成员。前者包括胃，肠道，淋巴系统，组织，肝，肺，心脏和脑的感染。实例包括旋毛虫病，淋巴丝虫病，盘尾丝虫病，血吸虫病，利什曼病，锥虫病，贾第虫病，球虫病和疟疾。
后者，即外寄生虫包括虱，蜱，螨，biting flies，蚤和蚊子。它们通常作为将体内寄生虫传播到人或动物宿主的载体和中间宿主。
尽管可以使用已知药物治疗某些蠕虫病，但是逐步发生耐药性要求在下一代驱虫药中对改善的功效进行进一步研究。
控制体内和体外寄生虫长期以来被视为人和动保健方案中的重要方面。传统的治疗通过口服或局部给药进行，且实际上这类治疗仍然在广泛应用。然而，现代强力推荐的研究已经倾向于开发可以通过口服或非肠道对动物给药并且在各寄生虫摄入治疗动物血液时杀灭各寄生虫来控制体内和体外寄生虫群体的化合物。
尽管大量杀外寄生虫药和杀内寄生虫药在应用中，但是它们存在各种问题，包括有限的活性谱，需要反复治疗和在许多情况中寄生虫产生耐药性。研发新的杀外寄生虫药和杀内寄生虫药治疗方法由此必需要确保安全性和对广泛寄生虫的有效控制。
公布的国际专利申请WO2001/076370中披露了驱虫组合物，其包含螺二噁庚因丙基并吲哚(spirodioxepinoindole)，特别是paraherquamide或marcfortine衍生物或类似物和大环内酯，特别是除虫菌素或米尔倍霉素衍生物或类似物。
较不易于产生耐药性的或对广泛寄生虫具有活性的活性剂的联合用药尤其需要。
发明概述
本发明的目的在于提供预防或治疗哺乳动物寄生虫疾病的方法，它广泛应用于一般对大环内酯类和其它类型的驱虫药产生耐药性的寄生虫。本发明的另一个目的在于提供新的驱虫组合物。本发明的另一个目的在于提供使用本发明的新组合物生产药物的方法。
本发明在第一个实施方案中提供了治疗哺乳动物寄生虫感染的方法，包括同时或依次对该哺乳动物给予有效量的(a)2-desoxoparaherquamide和(b)阿巴克丁的步骤。
本发明在另一个实施方案中提供了驱虫组合物，其包括(a)2-desoxoparaherquamide和(b)阿巴克丁。该组合物可以任选进一步包含药学上可接受的载体。
本发明在另一个实施方案中提供了上述组合物作为药物的应用。
本发明在另一个实施方案中提供了上述组合物在制备用于治疗或预防哺乳动物寄生虫疾病的药物中的应用。
本发明在另一个实施方案中提供了试剂盒，包括：(a)组合物：包含2-desoxoparaherquamide和任选药学上可接受的载体；和(b)阿巴克丁和任选的药学上可接受的载体，它们依次对哺乳动物给药。
本发明在另一个实施方案中提供了在毛圆线虫(trichostrongyloid nematodes)群体减少大环内酯耐受性个体的频率的方法，包括使用有效量的(a)2-desoxoparaherquamide和(b)阿巴克丁治疗这类群体的步骤。
发明详述
本发明涉及预防和治疗寄生虫攻击宿主哺乳动物的方法并且提供了用于控制寄生虫生物体的新的工具。特别地，本发明提供了这类治疗方法，包括使用：
2-desoxoparaherquamide；和
阿巴克丁。
所述哺乳动物可以为人或非人的哺乳动物。非人的哺乳动物包括可食用动物，农场动物和陪伴动物，例如牛，绵羊，山羊，猪，马，鹿，狗和猫。该治疗方法特别应用于绵羊和山羊，尤其是绵羊。
该治疗方法可以用于治疗广泛的寄生虫生物体。此外，应注意该治疗方法通过消除存在的寄生虫治疗具有存在寄生虫感染的动物。
有代表性的寄生虫生物体包括如下：
线形动物门(Nemathelminthes)，包括，例如，线形动物门(Ancylostoma)，管圆线虫属(Angiostrongylus)，异尖属(Anisakis)，蛔虫属(Ascaris)，布鲁丝虫属(Brugia)，仰口线虫(Bunostomum)，古柏线虫属(Cooperia)，夏柏特线虫(Chabertia)，杯口属(Cyathostomum)，杯环属(Cylicocyclus)，网尾线虫属(Dictyocaulus)(肺蠕虫)，棘唇属(Dipetalonema)，恶丝虫属(Dirofilaria)(恶丝虫)，龙线虫属(Dracunculus)，丝绒虫属(Elaeophora)，盖格线虫属(Gaigeria)，锥尾球头线虫(Globocephalus urosubulatus)，血矛线虫属(Haemonchus)，后圆线虫属(Metastrongylus)(肺蠕虫)，缪勒线虫(Muellerius)(肺蠕虫)，美洲板口线虫(Necator americanus)，细颈线虫属(Nematodirus)，结节线虫属(Oesophagostomum)，盘尾丝虫属(Onchocerca)，胃线虫属(Ostertagia)，副蛔虫属(Parascaris)，原圆线虫属(Protostrongylus)(肺蠕虫)，腹腔丝虫属(Setaria)，冠丝虫属(Stephanofilaria)，鸡张口丝虫属(Syngamus)，背带线虫属(Teladorsagia)，弓蛔线虫属(Toxascaris)，弓蛔虫属(Toxocara)，毛线虫属(Trichinella)，毛圆线虫属(Trichostrongylus)，鞭虫属(Trichuris)，狭头钩虫(Uncinariastenocephala)和班氏吴策线虫(Wuchereria bancrofti)；
节肢动物门(Arthropoda)，包括，例如，甲壳纲(Crustacea)，诸如波斯壁虱(Argulus)和鱼虱(Caligus)，蜘蛛纲(Arachnida)，诸如美洲钝眼蜱(Amblyomma americanum)(美洲花蜱)，斑点钝眼蜱(Amblyomma maculatum)(Gulf Coast tick)，波斯锐缘蜱(Argaspersicus)(家禽蜱)，微小牛蜱(Boophilus microplus)(牛蜱)，牛蠕螨(Demodex bovis)(cattle follicle mite)，犬脂螨(Demodexcanis)(狗毛囊螨)，安氏落矶山壁虱(Dermacentor andersoni)(洛矶山斑疹热蜱)，变异革蜱(Dermacentor variabilis)(美洲犬蜱)，鸡皮刺螨(Dermanyssus gallinae)(鸡螨)，蓖子硬蜱(lxodesricinus)(常见的羊蜱蝇)，鸡疥螨(Knemidokoptes gallinae)(deplumming mite)，鳞足螨(Knemidokoptes mutans)(鳞痂腿螨)，有刺耳朵壁虱(Otobius megnini)(耳残喙蜱)，马痒螨(Psoroptesequi)(痒螨)，羊痒螨(Psoroptes ovis)(痒螨)，血红扇头蜱(Rhipicephalus sanguineus)(褐色犬蜱)和疥螨(Sarcoptesscabiei)(兽疥螨)，昆虫纲(Insecta)，诸如伊蚊属(Aedes)(蚊子)，按蚊属(Anopheles)(蚊子)，库蚊属(Culex)(蚊子)，脉毛蚊属(Culiseta)(蚊子)，Bovicola bovis(牛虱)，雄旋皮蝇(Callitroga hominivorax)(绿头苍蝇)，斑虻属的种类(Chrysopsspp.)(斑虻)，温带臭虫(Cimex lectularius)(臭虫)，库蠓属的种类(Culicoides spp.)(蚋，白蛉，蠓或no-see-ums)，绵羊体虱(Damalinia ovis)(绵羊啮毛虱)，Dermaobia的种类(肤蝇)，红尾胃蝇(Gasterophilus haemorrhoidalis)(鼻热蝇)，肠胃蝇(Gasterophilus intestinalis)(常见的马热蝇)，鼻胃蝇(Gasterophilus nasalis)(chin fly)，舌蝇属的种类(Glossinaspp.)(采采蝇)，扰血蝇(Haematobia irritans)(角蝇，水牛蝇)，驴血虱(Haematopinus asini)(马吸吮虱)，牛血虱(Haematopinuseurysternus)(短鼻牛虱)，Haematopinus ovilius(体虱)，猪血虱(Haematopinus suis)(猪虱)，Hydrotaea irritans(head fly)，牛皮蝇(Hypoderma bovis)(bomb fly)，纹皮蝇(Hypoderma lineatum)(皮下蝇)，绵羊颚虱(Linognathus ovillus)(body louse)，足颚虱(Linognathus pedalis)(足虱)，狐颚虱(Linognathus vituli)(长鼻牛虱)，绿蝇属的种类(Lucilia spp.)(蛆蝇)，羊蜱(Melophagusovinus)(绵羊蜱蝇)，羊狂蝇(Oestrus ovis)(鼻热蝇)，黑花蝇(Phormia regina)(绿头苍蝇)，水牛盲虱(Solenopotes capillatus)(小蓝牛虱)。
该治疗方法特别用于控制蠕虫(helmith)寄生虫，包括线形动物门(Nemathelminthes)。
2-Desoxoparaherquamide(或称作2-deoxyparaherquamide)披露在美国专利US 5,750,695中，并且其合成描述在该专利的实施例37中。2-desoxoparaherquamide的结构式如式(I)中所示。
阿巴克丁(或称作除虫菌素B1)披露在美国专利US 4,310,519中。其为除虫菌素B1a(式(IIa))和除虫菌素B1b(式(IIb))的混合物，其中该混合物中的至少80％为B1a成分。
可以同时或依次给予所述两种成分。
本文所用的同时给药意旨在单次行为中对宿主动物给予两种成分，它需要将两种成分并入单一剂型，诸如单一口服溶液或混悬液，片剂或倾倒性溶液。
依次给药意旨每种成分的给药为单独的行为，但两次行为相连。例如，将给予包含一种成分的片剂和包含第二种成分的第二种片剂视为依次给药，即使将两种片剂同时对宿主动物给药也是如此。例如，将给予包含一种成分的液体制剂和包含第二种成分的第二种液体制剂视为依次给药，只要对宿主动物同时给予所述制剂或只要在给予一种制剂后即刻或短暂后对宿主动物给予另一种制剂。
为方便起见，可以优选同时给药。
两种药剂的确切给药剂量和频率取决于许多因素，包括(但不限于)所治疗具体病情的严重性，具体患者(人或动物)的年龄、体重和一般身体状况和患者可以服用的其它药物。这些因素为本领域技术人员众所周知的并且可以通过测定本发明组合物在患者血液中的浓度和/或患者对所治疗具体病情的反应来更确切地确定确切的剂量和频率。
一般而言，2-desoxoparaherquamide(2-DOPH)的给药量在约0.05-20mg/kg动物体重，将这类总剂量在一次或分次剂量中在诸如1-5天这类相对短的时间期限内给予。通过给予约0.1-10.0mg/kg体重单剂量获得对寄生虫的极佳控制。更具体地说，该剂量约为0.25-2mg/kg体重的单剂量。最具体地，该剂量约为2mg/kg体重的单剂量。
阿巴克丁给药量在约0.001-10mg/kg动物体重，将这类总剂量在一次或分次剂量中在诸如1-5天这类相对短的时间期限内给予。通过给予约0.025-0.5mg/kg体重的单剂量获得对寄生虫的极佳控制。更具体地说，该剂量约为0.025-0.2mg/kg体重的单剂量；最具体地，该剂量约为2mg/kg体重的单剂量。可以根据需要给予反复治疗以便抗击再感染并且取决于寄生虫的种类和使用的畜牧技术。用于对动物给予这些物质的技术对本领域技术人员而言为公知的。
可以通过任意合适的途径，包括口服，非肠道或局部给药给予所述药剂。当依次给予两种活性剂时，可以通过不同途径给予它们。一般可以将药剂并入进一步包含合适的赋形剂的制剂，其中所述制剂适合于提及的给药途径。当同时给予两种药剂时，将它们并入单一制剂。
为了进行口服给药，可以以诸如溶液，混悬液，胶囊，大丸剂，片剂或含药的饲料添加剂作为实例的剂型给予所述药剂。固体剂型(即非液体的)包含混合了功能性赋形剂的活性组分。这些赋形剂为生产胶囊，片剂，大丸剂或固体含药饲料添加剂领域普通技术人员众所周知的。视生产的剂型而定，通过不同方法制备这些固体剂型。制备制剂的普通技术人员熟知操作。
一般通过将活性成分与填充剂/增容粉末(例如乳糖，微晶纤维素)和可能的其它赋形剂、诸如有助于粉末流动的助流剂/润滑剂(例如硬脂酸镁，硬脂酸)和/或胶囊崩解剂(例如羟基乙酸淀粉钠，淀粉)混合制备胶囊。然后将这种包含活性成分的可流动粉末填充入硬壳胶囊。另一种类型的胶囊称作软胶囊(即软胶囊)。通过将活性成分与液体载体，诸如油(例如玉米油，芝麻油，分级分离的椰子油)混合且然后填充入软胶囊制备它们。
片剂为可以使用的第二种类的固体剂型。片剂使用赋形剂，所述赋形剂为稀释剂/填充剂(乳糖，磷酸二钙，微晶纤维素)，崩解剂(淀粉，羧甲基纤维素钠)，粘合剂(聚乙烯吡咯烷酮，甲基纤维素)和润滑剂/助流剂(硬脂酸，硬脂酸镁)。使用生产片剂的三种主要方法，包括直接压制，干法制粒和湿法制粒。在直接压制中，将所有赋形剂和活性成分一起混合而产生均匀混合物。然后将这种混合过的粉末进料入压片机，它通过将确定量的粉末压制成各单位片剂生产片剂。干法制粒包括将赋形剂与活性成分混合且然后使这种均匀混合物通过滚筒压制机。该滚筒压制机产生大的压紧物或条状物，然后可以用研磨机使其尺寸减小。这些较小的颗粒随即流动性良好并且可以放入压片机生产片剂。湿法制粒包括将活性成分与赋形剂混合且然后通过喷雾或混合加入液体(水，醇)。这种液体通常还包括粘合剂。将这种固体和液体混合物压过筛而产生颗粒并且干燥，只要使用传统的制粒法即可。或者，如果使用流化床干燥器，则在流化床干燥器中干燥颗粒。如果需要，可以用研磨机使这些颗粒尺寸减小且然后将它们与润滑剂混合并且进料入压片机生产片剂。
大丸剂为另一种可能的剂型。在本专利中的大丸剂意旨指定对较大动物给药的大片剂，通过上述方法或某些类似方式生产。或对动物口服给予的大固体剂型可以不同于常规片剂。
固体饲料添加剂为另一种可能的剂型。通过将活性成分与合适的饲料载体(稻米外壳，大豆外壳，磷酸二钙)混合生产这些产品而产生含药的A型制品，有时称作预混合物。还多次包括矿物油以便将粉尘减少到最低限度。将这些含药的A型制品或饲料添加剂进一步通过放入动物消耗的饲料稀释它们。这些饲料添加剂的另一种形式是形成含药的进料块，然后通过动物舔所述饲料块消耗活性剂。
更优选关注口服给药的液体制剂。因此，可以将所述药剂配制成在适合的水或非水液体介质中的混悬液，溶液或乳剂。非水介质可以包括，但不限于聚乙二醇，甘油甲醛，三醋精，丙二醇，n-甲基吡咯烷酮和各种油(例如花生油，矿物油，橄榄油，分级分分离的椰子油，葵花子油，大豆油，玉米油)。有时选择的油称作中链甘油三酯类，具有的商品名诸如810/820或
355。选择的另一种液体为丙二醇酯类，如丙二醇二-辛酸酯(
840)。这些非水介质可以包含微生物防腐剂(例如醇)和化学稳定剂(例如丁羟甲苯，维生素E)。水介质可以为含某些试剂的水，所述试剂诸如矫味强化剂(水果香料，蔗糖，葡萄糖)，微生物防腐剂(苄醇，苯甲酸，苯扎氯铵，缓冲剂(柠檬酸盐，磷酸盐)或pH调节剂(盐酸，氢氧化钠)。通过将活性剂分散于或溶于载体液体介质制备这些液体剂型，通过混合产生混悬液或溶液。易于溶混的液体也可以合并成共溶剂并且作为载体介质其作用。在某些情况中，如果需要可以将不易于溶混的液体与适当的乳化剂(例如卵磷脂)合并成微乳或乳剂。
非肠道给药的实例包括肌内，腹膜内，静脉内或皮下注射，其中将活性组分溶于或分散于液体载体介质和植入物和注入体内。就使用液体的非肠道给药而言，将活性物质与水或非水的可接受的介质适当混合。就使用植入物的非肠道给药而言，将活性成分配制成非肠道给药的固体或液体植入物。非肠道含水剂型可以由水与(如果需要)缓冲剂(例如柠檬酸盐，磷酸盐)，pH调节剂(盐酸，氢氧化钠)，微生物防腐剂(例如苄醇，苯甲酸，苯扎氯铵和化学稳定防腐剂(例如抗氧化剂，诸如棓酸丙酯，抗坏血酸)组成。非肠道非水剂型可以使用，但不限于聚乙二醇，甘油甲醛，三醋精，n-甲基吡咯烷酮，2-吡咯烷酮和各种油(例如花生油，矿物油，橄榄油，分级分分离的椰子油，葵花子油，大豆油，玉米油)。这些非水非肠道剂型还可以包括微生物防腐剂和化学稳定剂。还可以使用共溶剂(即两种或多种溶剂)。此外，不易混溶的溶剂组合形成乳剂可以为另一种非肠道给药剂型。通过将活性剂与相应的液体和任意的其它赋形剂混合生产非肠道剂型。这种混合在无菌条件下使用最终通过0.22微米滤膜过滤进行，以便产生无菌产品或使最终产物进行最终灭菌(例如加热，γ射线照射)而生成无菌注射用产品。
就局部给药而言，例如可以将药剂配制成倾倒性(pour-on)或点滴(spot-on)剂型。可以使用上述相同的水和非水介质。还可以使用粘度提高添加剂(例如羧甲纤维素，蜡)以便辅助保留在动物上或可以包括渗透促进剂(例如醇类)以便辅助增加全身吸收。使用本领域技术人员众所周知的方法生产局部剂型。在一种简单的方法中，将活性剂与溶剂和任意的添加剂混合而生成溶液或混悬液，然后可以将其倾倒或点在动物上。
用于动物的杀寄生虫药剂型有时称作灌服产品(drenchproducts)。可以通过局部或口服给予“灌服”剂型。使用术语“灌服”，因为突然将液体剂型给药入动物口腔/咽喉或倾倒(例如湿透)在动物皮肤/皮毛上。本专利意味着包括灌服制剂。
上述这类剂型(例如混悬液，溶液，胶囊，片剂，乳剂，大丸剂和固体饲料添加剂)可以根据其总重和抗寄生虫药的含量的不同在大范围内改变，这取决于诸如所治疗宿主动物的类型，感染类型的严重性和类型和宿主体重这类因素。
所述药剂可以与一种或多种额外的活性剂联用，并且可以将这些药剂并入作为给药制剂的组成部分。合适的额外的活性剂包括苯并咪唑类(诸如阿苯达唑，坎苯达唑，芬苯达唑，氟苯达唑，甲苯达唑，奥芬达唑，奥苯达唑和帕苯达唑)，咪唑并噻唑类(诸如四咪唑，左旋咪唑)和四氢嘧啶类(诸如双羟萘酸噻嘧啶，奥克太尔或莫仑太尔)，硝硫氰酯，抗寄生虫药噁唑啉类(诸如披露在US-5478855，US-4639771和DE-19520936中的那些)，如WO-9615121中所述的二氧代吗啉抗寄生虫药的一般类型的衍生物和类似物，环状缩酚肽类(诸如描述在WO-9611945，WO-9319053，WO-9325543，EP-626375，EP-382173，WO-9419334，EP-382173和EP-503538中的那些且特别是emodepside)，氟虫腈；除虫菊素类；有机磷酸盐(organophosphates)；昆虫生长调节剂(诸如氯芬奴隆)；蜕皮激素激动剂(诸如虫酰肼等)；多杀菌素(诸如Spinosad)，酰氨基乙腈类(诸如披露在WO-2005044784中的那些)；新烟碱类杀虫剂(诸如盖达落立等)；有机磷酸盐(诸如敌百虫，napthalophos，pyraclophos)；水杨酰苯胺类(诸如氯生太尔，氯硝柳胺)；Benzoenedisulphonmaide(诸如氯舒隆)；和pyrazinaisoquinoline(诸如吡喹酮)。
为了进行依次给药，可以将包含活性剂的组合物便利地制成试剂盒形式。这类试剂盒包含：两种或多种单独的药物组合物，其中至少一种包含2-desoxoparaherquamide，并且一种包含阿巴克丁；和分别保留所述组合物的装置，诸如容器，分开的瓶或分开的箔袋。
本发明的试剂盒特别适合于给予不同的剂型，例如口服和非肠道，适合于在不同剂量间隔给予单独的组合物或适合于交替着逐步增加各组合物的剂量。
尽管不希望受到任何具体科学理论的限制，但是认为2-desoxoparaherquamide与阿巴克丁的联合用药能够特异地减少trichostrongyloid群体中编码抗性蛋白的等位基因的频率，由此维持和恢复用于trichostrongyloid控制的蛋白质。
实施例1
在下列试验中证实联合用药的功效。
随机将五十四(54)只绵羊(Merino，无论是否为一岁以上的羊)指定为9组之一。在本试验的-41天，用驱虫磷和左旋咪唑治疗绵羊以便除去任何预先存在的寄生虫负担。在本试验的-27天时收集粪便样品并且分析以便证实根除寄生虫。在-24天，通过瘤胃内注射下列寄生虫从而使绵羊感染：
·约3000 3rd阶段(L3)Kirby易感性菌株捻转血矛线虫(Haemonchus contortus)
·约6000 3rd阶段(L3)McMaster易感性菌株Teladorsagiacircumcincta
·约6000 3rd阶段(L3)McMaster易感性菌株蛇形毛圆线虫(Trichostrongylus colubriformis)
在本试验的-1天收集粪便样品并且测定卵计数。
在本试验的0天，按照下列方案治疗绵羊。
| 组 | 动物数 | 制剂 | 2-DOPH的剂量* | ABA的剂量* |
| G1 | 6 | 无治疗(阴性对照) | 0 | 0 |
| G2 | 6 | F1 | 2mg/kg | 0.2mg/kg |
| G3 | 6 | F1 | 1mg/kg | 0.1mg/kg |
| G4 | 6 | F1 | 0.5mg/kg | 0.05mg/kg |
| G5 | 6 | F1 | 0.25mg/kg | 0.025mg/kg |
| G6 | 6 | F2 | 2mg/kg | 0.2mg/kg |
| G7 | 6 | F2 | 1mg/kg | 0.1mg/kg |
| G8 | 6 | F2 | 0.5mg/kg | 0.05mg/kg |
| G9 | 6 | F2 | 0.25mg/kg | 0.025mg/kg |
*2-DOPH＝2-desoxoparaherquamide；ABA＝阿巴克丁
制剂F1包含2-DOPH(10mg/mL)，ABA(1.0mg/mL)，甘油甲醛(50mg/mL)，丁羟甲苯(0.5mg/mL)和三醋精(1096.8mg/mL)。
制剂F2包含2-DOPH(10mg/mL)，ABA(1.0mg/mL)，甘油甲醛(50mg/mL)，丁羟甲苯(0.5mg/mL)，三醋精(400mg/mL)和丙二醇二-辛酸酯(550.8mg/mL)。
在本试验的13，14和15天时处死每种的2只动物。分析胃肠器官和粪便样品作为剩余寄生虫感染的证据。
粪便卵计数
| 组 | 卵计数的组几何平均值 | ％功效 |
| G1 | 11921.4 | |
| G2 | 0.9 | 99.99 |
| G3 | 0.0 | ＞99.99 |
| G4 | 1.1 | 99.99 |
| G5 | 37.6 | 99.68 |
| G6 | 0.0 | ＞99.99 |
| G7 | 0.9 | 99.99 |
| G8 | 0.0 | ＞99.99 |
| G9 | 11.3 | 99.90 |
总虫计数
实施例2
绵羊肠胃道寄生虫的抗性菌株的治疗
用Teladorsagia(Ostertagia)普通奥斯特他线虫(circumcincta)和蛇形毛圆线虫的L3幼虫人工感绵羊并且根据给予治疗后治疗组中的总虫计数与对照组比较确定功效。如下所述使用商购的包括的对照产品治疗动物以便证实上述寄生虫的耐药性特性。
| 治疗组 | 测试/对照产品 | 剂量比例 | 剂量体积 | 途径 | 频率 | 治疗天 | 动物数 |
| T01 | 安慰剂(自来水) | N/A | 0.20mL/kg | 口服 | 一次 | 第0天 | 10 |
| T02 | 2-DOPH+阿巴克丁 | 2mg/kg0.2mg/kg | 0.20mL/kg | 口服 | 一次 | 第0天 | 10 |
| T03 | 阿苯达唑 | 3.8mg/kg | 0.15mL/kg | 口服 | 一次 | 第0天 | 10 |
| T04 | 左旋咪唑 | 8mg/kg | 0.20mL/kg | 口服 | 一次 | 第0天 | 10 |
| T05 | 伊维菌素 | 0.2mg/kg | 0.25mL/kg | 口服 | 一次 | 第0天 | 10 |
在治疗后第15天时对全部研究动物进行尸检。采集皱胃和小肠以获得虫和用于总虫计数估计。
2-DOPH/阿巴克丁，阿苯达唑，左旋咪唑和伊维菌素对绵羊中三种胃肠道线虫的耐药株的虫计数组算术平均值，p-值和治疗功效(治疗后15天)。
总虫计数
^NEG＝无功效；因平均计数的在治疗组中高于对照组(T01)未计算功效
本研究表明伊维菌素(与阿巴克丁相同类型的化合物)对Teladorsagia circumcincta的功效为0％；且2-DOPH/阿巴克丁的联合用药对Teladorsagia circumcincta的功效为100％；因此，这一发现令人意外和未预料到。
实施例3
绵羊肠胃道寄生虫的抗性菌株的治疗
用含有捻转血矛线虫，背带线虫属的种类和毛圆线虫属的种类的混合培养基中的L3幼虫人工感绵羊，并且根据给予治疗后治疗组中的总虫计数与对照组比较确定功效。如下所述使用商购的包括的对照产品治疗动物以便证实上述寄生虫的耐药性特性。
| 治疗组 | 测试/对照产品 | 剂量比例 | 剂量体积 | 途径 | 频率 | 治疗天 | 动物数 |
| T01 | 安慰剂(自来水) | N/A | 0.2mL/kg | 口服 | 一次 | 第0天 | 10 |
| T02 | 2-DOPH+阿巴克丁 | 2mg/kg0.2mg/kg | 0.2mL/kg | 口服 | 一次 | 第0天 | 10 |
| T03 | 阿苯达唑 | 3.8mg/kg | 0.15mL/kg | 口服 | 一次 | 第0天 | 10 |
| T04 | 左旋咪唑 | 8mg/kg | 0.20mL/kg | 口服 | 一次 | 第0天 | 10 |
| T05 | 伊维菌素 | 0.2mg/kg | 0.25mL/kg | 口服 | 一次 | 第0天 | 10 |
在治疗后第15天时对全部研究动物进行尸检。采集皱胃和小肠以获得虫和用于总虫计数估计。
总虫计数
上述实施例表明了额外的研究，即，即使对大环内酯类化合物产生抗性时2-DOPH/阿巴克丁联合用药也表现出很高的功效。
Claims (10)
1.2-desoxoparaherquamide和阿巴克丁在制备治疗哺乳动物寄生虫感染的药物中的应用。
2.权利要求1的应用，其中所述寄生虫为蠕虫。
3.权利要求1的应用，其中所述哺乳动物为非人的哺乳动物。
4.权利要求3的应用，其中所述非人的哺乳动物为绵羊。
5.驱虫组合物，包含：(a)2-desoxoparaherquamide；和(b)阿巴克丁。
6.权利要求5的组合物，其进一步包含药学上可接受的载体。
7.权利要求5的组合物作为药物的使用。
8.试剂盒，包含：(a)组合物，所述组合物包含2-desoxoparaherquamide和任选的药学上可接受的载体；和(b)阿巴克丁和任选的药学上可接受的载体，它们用于依次对哺乳动物给药。
9.2-desoxoparaherquamide和阿巴克丁在制备药物中的应用，所述药物用以减少毛圆线虫(trichostrongyloid nematodes)群体中驱虫药抗性基因的频率。
10.2-desoxoparaherquamide和阿巴克丁的组合在制备用于治疗哺乳动物寄生虫感染的药物中的应用。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94701507P | 2007-06-29 | 2007-06-29 | |
| US60/947,015 | 2007-06-29 | ||
| PCT/IB2008/001638 WO2009004432A1 (en) | 2007-06-29 | 2008-06-16 | Anthelmintic combination |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101686962A true CN101686962A (zh) | 2010-03-31 |
| CN101686962B CN101686962B (zh) | 2012-05-23 |
Family
ID=39831661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008800226439A Expired - Fee Related CN101686962B (zh) | 2007-06-29 | 2008-06-16 | 驱虫药联合用药 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US8440633B2 (zh) |
| EP (1) | EP2170321B1 (zh) |
| JP (1) | JP5462456B2 (zh) |
| CN (1) | CN101686962B (zh) |
| AR (1) | AR067347A1 (zh) |
| AU (1) | AU2008272646B2 (zh) |
| BR (1) | BRPI0813235B1 (zh) |
| CA (1) | CA2690111C (zh) |
| CY (1) | CY1114363T1 (zh) |
| DK (1) | DK2170321T3 (zh) |
| ES (1) | ES2423505T3 (zh) |
| NZ (1) | NZ581859A (zh) |
| PL (1) | PL2170321T3 (zh) |
| PT (1) | PT2170321E (zh) |
| TW (1) | TWI352592B (zh) |
| WO (1) | WO2009004432A1 (zh) |
| ZA (1) | ZA201000672B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113194937A (zh) * | 2018-10-04 | 2021-07-30 | 礼蓝动物健康股份公司 | 蠕虫治疗的增强 |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS58508B1 (sr) | 2008-11-14 | 2019-04-30 | Merial Inc | Enantiomerno obogaćena paraziticidalna jedinjenja ariloazol-2-il cijanoetilamino |
| BRPI0922043B1 (pt) | 2008-11-19 | 2019-04-24 | Merial, Inc. | Composições compreendendo um aril pirazol e/ou formamidina, métodos e usos das mesmas |
| TWI457347B (zh) | 2008-12-04 | 2014-10-21 | Merial Ltd | 二聚合的阿佛菌素（ａｖｅｒｍｅｃｔｉｎ）及密倍脈心（ｍｉｌｂｅｍｙｃｉｎ）衍生物 |
| CN102712583B (zh) | 2009-12-04 | 2015-04-08 | 梅里亚有限公司 | 农药用双-有机硫化合物 |
| SI3078664T1 (sl) | 2009-12-17 | 2019-05-31 | Merial Inc. | Antiparazitski dihidroazolni sestavki |
| US8980896B2 (en) | 2009-12-17 | 2015-03-17 | Merial, Inc. | Compositions comprising macrocyclic lactone compounds and spirodioxepinoindoles |
| UA108641C2 (uk) | 2010-04-02 | 2015-05-25 | Паразитицидна композиція, яка містить чотири активних агенти, та спосіб її застосування | |
| LT2640728T (lt) | 2010-11-16 | 2017-03-27 | Merial, Inc. | Nauji monenzino dariniai, skirti pirmuonių sukeltų infekcijų gydymui |
| US20120329832A1 (en) | 2011-06-27 | 2012-12-27 | Jean Delaveau | Novel Insect-Repellent Coumarin Derivatives, Syntheses, and Methods of Use |
| EA201400058A1 (ru) | 2011-06-27 | 2014-07-30 | Мериал Лимитед | Соединения и композиции на основе амидопиридиловых эфиров и их применение против паразитов |
| BR122019001738B1 (pt) | 2011-09-12 | 2019-11-05 | Merial Inc | composições parasiticidas compreendendo um agente ativo de isoxazolina e usos das mesmas |
| WO2013044118A2 (en) | 2011-09-23 | 2013-03-28 | Merial Limited | Indirect modeling of new repellent molecules active against insects, acarids, and other arthropods |
| US9173404B2 (en) | 2011-11-17 | 2015-11-03 | Merial, Inc. | Compositions comprising an aryl pyrazole and a substituted imidazole, methods and uses thereof |
| MX358476B (es) | 2011-12-02 | 2018-08-22 | Merial Ltd | Formulaciones de moxidectina inyectables de larga acción y formas de cristal de moxidectina novedosas. |
| BR122020022192B1 (pt) | 2012-02-06 | 2021-12-07 | Merial, Inc | Composições orais veterinárias parasíticas compreendendo ingredientes ativos de ação sistêmica, métodos e uso das mesmas |
| JO3626B1 (ar) | 2012-02-23 | 2020-08-27 | Merial Inc | تركيبات موضعية تحتوي على فيبرونيل و بيرميثرين و طرق استخدامها |
| MX367536B (es) | 2012-04-20 | 2019-08-26 | Boehringer Ingelheim Animal Health Usa Inc | Composiciones parasiticidas que comprenden derivados de benzimidazol, métodos y usos de los mismos. |
| RS57779B1 (sr) | 2012-11-20 | 2018-12-31 | Merial Inc | Antihelmintska jedinjenja i kompozicije i postupak za njihovu upotrebu |
| NZ719916A (en) | 2013-11-01 | 2017-09-29 | Merial Inc | Antiparasitic and pesticidal isoxazoline compounds |
| CA2945766C (en) | 2014-04-17 | 2023-09-26 | Merial, Inc. | Use of malononitrile compounds for protecting animals from parasites |
| EP3145925B1 (en) | 2014-05-19 | 2020-11-04 | Boehringer Ingelheim Animal Health USA Inc. | Anthelmintic compounds |
| EP3157912B1 (en) | 2014-06-19 | 2019-02-20 | Merial, Inc. | Parasiticidal compositions comprising indole derivatives, methods and uses thereof |
| WO2016069983A1 (en) | 2014-10-31 | 2016-05-06 | Merial, Inc. | Parasiticidal composition comprising fipronil |
| UY36570A (es) | 2015-02-26 | 2016-10-31 | Merial Inc | Formulaciones inyectables de acción prolongada que comprenden un agente activo isoxazolina, métodos y usos de las mismas |
| NZ737610A (en) | 2015-05-20 | 2023-07-28 | Boehringer Ingelheim Animal Health Usa Inc | Anthelmintic depsipeptide compounds |
| UY37137A (es) | 2016-02-24 | 2017-09-29 | Merial Inc | Compuestos antiparasitarios de isoxazolina, formulaciones inyectables de acción prolongada que los comprenden, métodos y usos de los mismos |
| WO2018039508A1 (en) | 2016-08-25 | 2018-03-01 | Merial, Inc. | Method for reducing unwanted effects in parasiticidal treatments |
| AU2017344097A1 (en) | 2016-10-14 | 2019-05-02 | Boehringer Ingelheim Animal Health USA Inc. | Pesticidal and parasiticidal vinyl isoxazoline compounds |
| MX2019005628A (es) | 2016-11-16 | 2019-12-18 | Boehringer Ingelheim Animal Health Usa Inc | Compuestos depsipeptidos antihelminticos. |
| CA3072936A1 (en) | 2017-08-14 | 2019-02-21 | Boehringer Ingelheim Animal Health USA Inc. | Pesticidal and parasiticidal pyrazole-isoxazoline compounds |
| EP3749096A1 (en) | 2018-02-08 | 2020-12-16 | Boehringer Ingelheim Animal Health USA Inc. | Parasiticidal compositions comprising eprinomectin and praziquantel, methods and uses thereof |
| CA3106092A1 (en) | 2018-07-09 | 2020-01-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anthelminthic heterocyclic compounds |
| CN113260419A (zh) | 2018-11-20 | 2021-08-13 | 勃林格殷格翰动物保健美国公司 | 吲唑基氰基乙基氨基化合物、其组合物、其制备方法和其使用方法 |
| CA3129329A1 (en) | 2019-03-01 | 2020-09-10 | Boehringer Ingelheim Animal Health USA Inc. | Injectable clorsulon compositions, methods and uses thereof |
| SG11202109786UA (en) | 2019-03-19 | 2021-10-28 | Boehringer Ingelheim Animal Health Usa Inc | Anthelmintic aza-benzothiophene and aza-benzofuran compounds |
| WO2021242581A1 (en) | 2020-05-29 | 2021-12-02 | Boehringer Ingelheim Animal Health USA Inc. | Anthelmintic heterocyclic compounds |
| US20220201983A1 (en) | 2020-12-21 | 2022-06-30 | Boehringer Ingelheim Animal Health USA Inc. | Parasiticidal collar comprising isoxazoline compounds |
| WO2023156938A1 (en) | 2022-02-17 | 2023-08-24 | Boehringer Ingelheim Vetmedica Gmbh | Method and system for providing a fluid product mailer |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ207655A (en) * | 1983-04-07 | 1986-09-10 | Merck & Co Inc | Synergistic veterinary compositions containing an avermectin compound and clorsulon |
| GB2221621A (en) * | 1988-08-12 | 1990-02-14 | Merck & Co Inc | Synergistic antiparasitic combinations of avermectin and pyrantel |
| PE20011289A1 (es) * | 2000-04-07 | 2001-12-21 | Upjohn Co | Composiciones antihelminticas que comprenden lactonas macrociclicas y espirodioxepinoindoles |
| AU2003900505A0 (en) * | 2003-02-05 | 2003-02-20 | Jurox Pty Ltd | Anthelmintic composition |
-
2008
- 2008-06-16 DK DK08762949.9T patent/DK2170321T3/da active
- 2008-06-16 PL PL08762949T patent/PL2170321T3/pl unknown
- 2008-06-16 NZ NZ581859A patent/NZ581859A/en unknown
- 2008-06-16 BR BRPI0813235A patent/BRPI0813235B1/pt active IP Right Grant
- 2008-06-16 PT PT87629499T patent/PT2170321E/pt unknown
- 2008-06-16 US US12/666,143 patent/US8440633B2/en active Active
- 2008-06-16 CA CA2690111A patent/CA2690111C/en active Active
- 2008-06-16 CN CN2008800226439A patent/CN101686962B/zh not_active Expired - Fee Related
- 2008-06-16 AU AU2008272646A patent/AU2008272646B2/en active Active
- 2008-06-16 WO PCT/IB2008/001638 patent/WO2009004432A1/en active Application Filing
- 2008-06-16 ES ES08762949T patent/ES2423505T3/es active Active
- 2008-06-16 EP EP08762949.9A patent/EP2170321B1/en active Active
- 2008-06-27 AR ARP080102793A patent/AR067347A1/es not_active Application Discontinuation
- 2008-06-27 TW TW097124413A patent/TWI352592B/zh not_active IP Right Cessation
- 2008-06-30 JP JP2008169818A patent/JP5462456B2/ja not_active Expired - Fee Related
-
2010
- 2010-01-28 ZA ZA201000672A patent/ZA201000672B/xx unknown
-
2013
- 2013-08-09 CY CY20131100683T patent/CY1114363T1/el unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113194937A (zh) * | 2018-10-04 | 2021-07-30 | 礼蓝动物健康股份公司 | 蠕虫治疗的增强 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2690111A1 (en) | 2009-01-08 |
| ES2423505T3 (es) | 2013-09-20 |
| US8440633B2 (en) | 2013-05-14 |
| CN101686962B (zh) | 2012-05-23 |
| WO2009004432A1 (en) | 2009-01-08 |
| BRPI0813235B1 (pt) | 2019-01-22 |
| AU2008272646B2 (en) | 2013-08-22 |
| EP2170321B1 (en) | 2013-05-22 |
| CA2690111C (en) | 2011-11-15 |
| PL2170321T3 (pl) | 2013-12-31 |
| JP2009051820A (ja) | 2009-03-12 |
| DK2170321T3 (da) | 2013-07-29 |
| PT2170321E (pt) | 2013-08-01 |
| TW200918044A (en) | 2009-05-01 |
| CY1114363T1 (el) | 2016-08-31 |
| JP5462456B2 (ja) | 2014-04-02 |
| ZA201000672B (en) | 2010-10-27 |
| US20100197624A1 (en) | 2010-08-05 |
| AR067347A1 (es) | 2009-10-07 |
| BRPI0813235A2 (pt) | 2014-12-23 |
| EP2170321A1 (en) | 2010-04-07 |
| NZ581859A (en) | 2012-06-29 |
| TWI352592B (en) | 2011-11-21 |
| AU2008272646A1 (en) | 2009-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101686962B (zh) | 驱虫药联合用药 | |
| JP2003529614A (ja) | 新規駆虫組成物 | |
| EP2892347B1 (en) | Spirocyclic isoxazoline parasiticidal combinations | |
| CN1972672A (zh) | 含有非动物产品的兽用制剂 | |
| US11896594B2 (en) | Palatable antiparasitic formulations | |
| DK1957040T3 (en) | Non-aqueous benzimidazolsammensætninger | |
| CN101848710A (zh) | 驱虫用组合物 | |
| EP1940396B1 (en) | Anthelmintic formulations | |
| AU2014332597A1 (en) | Veterinary formulations and methods | |
| RU2773154C1 (ru) | Противопаразитарные составы с привлекательным вкусом | |
| WO2017017091A1 (fr) | Nouvelles compositions vétérinaires pour la prévention et le traitement simultané des endoparasites et ectoparasites | |
| CN103181925A (zh) | 一种复方非班太尔凝胶剂及其制备方法 | |
| WO2010126857A1 (en) | Parasiticidal combinations of macrocyclic lactones and polyether antibiotics | |
| NZ617203A (en) | Ectoparasitic treatment method and composition | |
| NZ617203B2 (en) | Ectoparasitic treatment method and composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: AH USA 42 LLC Free format text: FORMER OWNER: SMITHKLINE BEECHAM PLC Effective date: 20130613 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| C56 | Change in the name or address of the patentee |
Owner name: SHUOTENG CO., LTD. Free format text: FORMER NAME: AH USA 42 LLC |
|
| CP01 | Change in the name or title of a patent holder |
Address after: American New York Patentee after: Pfizer Inc. Address before: American New York Patentee before: Ah USA 42 LLC |
|
| CP02 | Change in the address of a patent holder |
Address after: American New Jersey Patentee after: Pfizer Inc. Address before: American New York Patentee before: Pfizer Inc. |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20130613 Address after: American New York Patentee after: Ah USA 42 LLC Address before: American New York Patentee before: PFIZER Inc. |
|
| ASS | Succession or assignment of patent right |
Owner name: SHUOTENG SERVICE LLC Free format text: FORMER OWNER: SHUOTENG CO., LTD. Effective date: 20150729 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20150729 Address after: New jersey, USA Patentee after: Zoetis Services LLC Address before: American New Jersey Patentee before: Pfizer Inc. |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120523 Termination date: 20170616 |