CN1113651C - 喹诺酮羧酸或萘啶酮羧酸的口服制剂 - Google Patents
喹诺酮羧酸或萘啶酮羧酸的口服制剂 Download PDFInfo
- Publication number
- CN1113651C CN1113651C CN97197362A CN97197362A CN1113651C CN 1113651 C CN1113651 C CN 1113651C CN 97197362 A CN97197362 A CN 97197362A CN 97197362 A CN97197362 A CN 97197362A CN 1113651 C CN1113651 C CN 1113651C
- Authority
- CN
- China
- Prior art keywords
- acid
- preparation
- water
- derivant
- water soluble
- 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.)
- Expired - Fee Related
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 43
- 238000009472 formulation Methods 0.000 title claims abstract description 7
- -1 naphthyridone carboxylic acids Chemical class 0.000 title description 9
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 11
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 claims description 16
- 241001597008 Nomeidae Species 0.000 claims description 16
- 229960000740 enrofloxacin Drugs 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical compound C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 claims description 11
- RLLPVAHGXHCWKJ-UHFFFAOYSA-N permethrin Chemical compound CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 RLLPVAHGXHCWKJ-UHFFFAOYSA-N 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 239000011363 dried mixture Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 38
- 238000002156 mixing Methods 0.000 abstract description 2
- 150000007513 acids Chemical class 0.000 abstract 2
- 239000012266 salt solution Substances 0.000 abstract 2
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 19
- 239000008187 granular material Substances 0.000 description 14
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 11
- 241000282898 Sus scrofa Species 0.000 description 11
- 241000283690 Bos taurus Species 0.000 description 8
- 235000019688 fish Nutrition 0.000 description 7
- 241000251468 Actinopterygii Species 0.000 description 6
- 239000003086 colorant Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000035143 Bacterial infection Diseases 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 241001494479 Pecora Species 0.000 description 5
- 208000022362 bacterial infectious disease Diseases 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- 241000283073 Equus caballus Species 0.000 description 4
- 241000287828 Gallus gallus Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 241000607598 Vibrio Species 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-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
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 241001430197 Mollicutes Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010035664 Pneumonia Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000194017 Streptococcus Species 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000174 gluconic acid Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 2
- FEOHYDSNGHIXOM-WLDMJGECSA-N (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)-2-methyloxane-2,4,5-triol Chemical compound CC1(O)[C@H](N)[C@@H](O)[C@H](O)[C@H](O1)CO FEOHYDSNGHIXOM-WLDMJGECSA-N 0.000 description 2
- XBHBWNFJWIASRO-UHFFFAOYSA-N 6-fluoro-1-(4-fluorophenyl)-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1=CC=C(F)C=C1 XBHBWNFJWIASRO-UHFFFAOYSA-N 0.000 description 2
- 241000607534 Aeromonas Species 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000238424 Crustacea Species 0.000 description 2
- 241000252233 Cyprinus carpio Species 0.000 description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- QMLVECGLEOSESV-RYUDHWBXSA-N Danofloxacin Chemical compound C([C@@H]1C[C@H]2CN1C)N2C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=CC=1N2C1CC1 QMLVECGLEOSESV-RYUDHWBXSA-N 0.000 description 2
- 241000607473 Edwardsiella <enterobacteria> Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000588748 Klebsiella 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
- 206010024238 Leptospirosis Diseases 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
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 206010037151 Psittacosis Diseases 0.000 description 2
- 241000190932 Rhodopseudomonas Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000186064 Trueperella pyogenes Species 0.000 description 2
- 206010047400 Vibrio infections Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 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 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 235000019658 bitter taste Nutrition 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 229960004385 danofloxacin Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 150000004665 fatty acids Chemical group 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000004611 light stabiliser Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 208000004396 mastitis Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 201000000901 ornithosis Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229950007734 sarafloxacin Drugs 0.000 description 2
- 230000014860 sensory perception of taste Effects 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- QKDHBVNJCZBTMR-LLVKDONJSA-N (R)-temafloxacin Chemical compound C1CN[C@H](C)CN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1=CC=C(F)C=C1F QKDHBVNJCZBTMR-LLVKDONJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-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
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- ZQHYXNSQOIDNTL-UHFFFAOYSA-N 3-hydroxyglutaric acid Chemical compound OC(=O)CC(O)CC(O)=O ZQHYXNSQOIDNTL-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- QVADRSWDTZDDGR-UHFFFAOYSA-N 5-oxotetrahydrofuran-2-carboxylic acid Chemical compound OC(=O)C1CCC(=O)O1 QVADRSWDTZDDGR-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- UBGCCYGMLOBJOJ-UHFFFAOYSA-N 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN2CCC1CC2 UBGCCYGMLOBJOJ-UHFFFAOYSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000606750 Actinobacillus Species 0.000 description 1
- 241000186042 Actinomyces bovis Species 0.000 description 1
- 241000186041 Actinomyces israelii Species 0.000 description 1
- 241000203716 Actinomycetaceae Species 0.000 description 1
- 241000607525 Aeromonas salmonicida Species 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 241000122170 Aliivibrio salmonicida Species 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241001112741 Bacillaceae Species 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000606660 Bartonella Species 0.000 description 1
- 241000606662 Bartonellaceae Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000588779 Bordetella bronchiseptica Species 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- 208000003508 Botulism Diseases 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- 241001148106 Brucella melitensis Species 0.000 description 1
- 241001148111 Brucella suis Species 0.000 description 1
- 241000589513 Burkholderia cepacia Species 0.000 description 1
- 241000722910 Burkholderia mallei Species 0.000 description 1
- 206010069747 Burkholderia mallei infection Diseases 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 206010051226 Campylobacter infection Diseases 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241001597062 Channa argus Species 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 241001647378 Chlamydia psittaci Species 0.000 description 1
- 241000606069 Chlamydiaceae Species 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 241000272205 Columba livia Species 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 241001445332 Coxiella <snail> Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 241000270722 Crocodylidae Species 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000723298 Dicentrarchus labrax Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241000371997 Eriocheir sinensis Species 0.000 description 1
- 201000000297 Erysipelas Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010017553 Furuncle Diseases 0.000 description 1
- 241000605909 Fusobacterium Species 0.000 description 1
- 206010017564 Fusobacterium infections Diseases 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- 201000003641 Glanders Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- BPFYOAJNDMUVBL-UHFFFAOYSA-N LSM-5799 Chemical compound C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3N(C)COC1=C32 BPFYOAJNDMUVBL-UHFFFAOYSA-N 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 241000589902 Leptospira Species 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 206010024641 Listeriosis Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000721576 Melopsittacus undulatus Species 0.000 description 1
- 241000192017 Micrococcaceae Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000588621 Moraxella Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001508687 Mustela erminea Species 0.000 description 1
- 241000186360 Mycobacteriaceae Species 0.000 description 1
- 241000186367 Mycobacterium avium Species 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 241000204034 Mycoplasmataceae Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 206010028846 Necrobacillosis Diseases 0.000 description 1
- 241000187678 Nocardia asteroides Species 0.000 description 1
- 241001503673 Nocardia farcinica Species 0.000 description 1
- 241001655308 Nocardiaceae Species 0.000 description 1
- QIPQASLPWJVQMH-DTORHVGOSA-N Orbifloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(F)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F QIPQASLPWJVQMH-DTORHVGOSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000026681 Paratuberculosis Diseases 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 206010034107 Pasteurella infections Diseases 0.000 description 1
- 241000606856 Pasteurella multocida Species 0.000 description 1
- 241000927735 Penaeus Species 0.000 description 1
- 241000238552 Penaeus monodon Species 0.000 description 1
- 241000206591 Peptococcus Species 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 208000035109 Pneumococcal Infections Diseases 0.000 description 1
- 206010035673 Pneumonia chlamydial Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000588768 Providencia Species 0.000 description 1
- 241000947836 Pseudomonadaceae Species 0.000 description 1
- 206010037132 Pseudomonal infections Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000520869 Pseudomonas anguilliseptica Species 0.000 description 1
- 241000589540 Pseudomonas fluorescens Species 0.000 description 1
- 241001404174 Psittacula alexandri fasciata Species 0.000 description 1
- 208000006311 Pyoderma Diseases 0.000 description 1
- 244000184734 Pyrus japonica Species 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 241000186813 Renibacterium Species 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 208000034712 Rickettsia Infections Diseases 0.000 description 1
- 241000606683 Rickettsiaceae Species 0.000 description 1
- 206010061495 Rickettsiosis Diseases 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010039438 Salmonella Infections Diseases 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000276699 Seriola Species 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000253368 Spirillaceae Species 0.000 description 1
- 241000589971 Spirochaetaceae Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000122973 Stenotrophomonas maltophilia Species 0.000 description 1
- 241001478878 Streptobacillus Species 0.000 description 1
- 241000194018 Streptococcaceae Species 0.000 description 1
- 206010061372 Streptococcal infection Diseases 0.000 description 1
- 241000193985 Streptococcus agalactiae Species 0.000 description 1
- 241000194042 Streptococcus dysgalactiae Species 0.000 description 1
- 241000194048 Streptococcus equi Species 0.000 description 1
- 241000194054 Streptococcus uberis Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 206010046793 Uterine inflammation Diseases 0.000 description 1
- 241000544286 Vibrio anguillarum Species 0.000 description 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- 208000025087 Yersinia pseudotuberculosis infectious disease Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 201000007691 actinomycosis Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 230000037006 agalactosis Effects 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-ASMJPISFSA-N alpha-maltose 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-ASMJPISFSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 210000001557 animal structure Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229950011614 binfloxacin Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940038698 brucella melitensis Drugs 0.000 description 1
- 229940074375 burkholderia mallei Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 241000186254 coryneform bacterium Species 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- LNNWVNGFPYWNQE-GMIGKAJZSA-N desomorphine Chemical compound C1C2=CC=C(O)C3=C2[C@]24CCN(C)[C@H]1[C@@H]2CCC[C@@H]4O3 LNNWVNGFPYWNQE-GMIGKAJZSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- NOCJXYPHIIZEHN-UHFFFAOYSA-N difloxacin Chemical compound C1CN(C)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1=CC=C(F)C=C1 NOCJXYPHIIZEHN-UHFFFAOYSA-N 0.000 description 1
- 229950001733 difloxacin Drugs 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000001848 dysentery Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 210000004905 finger nail Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 208000003512 furunculosis Diseases 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 210000000003 hoof Anatomy 0.000 description 1
- 125000000687 hydroquinonyl group Chemical class C1(O)=C(C=C(O)C=C1)* 0.000 description 1
- DXKRGNXUIRKXNR-UHFFFAOYSA-N ibafloxacin Chemical compound C1CC(C)N2C=C(C(O)=O)C(=O)C3=C2C1=C(C)C(F)=C3 DXKRGNXUIRKXNR-UHFFFAOYSA-N 0.000 description 1
- 229950007954 ibafloxacin Drugs 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 229940099563 lactobionic acid 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
- 239000007788 liquid Substances 0.000 description 1
- 241000238565 lobster Species 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229960002531 marbofloxacin Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 229960004780 orbifloxacin Drugs 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 206010033072 otitis externa Diseases 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 201000005115 pasteurellosis Diseases 0.000 description 1
- 235000010603 pastilles Nutrition 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
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 201000006509 pleuropneumonia Diseases 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- SUQUWONDIBHQOZ-NWDGAFQWSA-N premafloxacin Chemical compound C1[C@H]([C@H](C)NC)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1OC SUQUWONDIBHQOZ-NWDGAFQWSA-N 0.000 description 1
- 229950002166 premafloxacin Drugs 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 206010039447 salmonellosis Diseases 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229940115920 streptococcus dysgalactiae Drugs 0.000 description 1
- 229940115922 streptococcus uberis Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960004576 temafloxacin Drugs 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- JATLJHBAMQKRDH-UHFFFAOYSA-N vebufloxacin Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)CCC3=C1N1CCN(C)CC1 JATLJHBAMQKRDH-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000003871 white petrolatum Substances 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
- A61K31/33—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
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明涉及喹诺酮羧酸或萘啶酮羧酸口服制剂的制备方法，该方法为在有赋形剂、有或无辅助剂的情况下，将喹诺酮羧酸或萘啶酮羧酸或其水溶性盐或衍生物(优选其水性盐溶液)与扑酸或其水溶性盐或衍生物(优选其水性盐溶液)混合，在使用干燥的混合物时在水中混合，并且，需要的话，将所得的混合物进一步转化为适于使用的形式。
Description
技术领域
本发明涉及喹诺酮羧酸或萘啶酮羧酸的口服制剂的制备方法以及由该方法制得的制剂。
背景技术 喹诺酮羧酸的扑酸盐是已知的，例如参见EP-A(欧洲公开说明书)238814。它们用于制备通过与扑酸成盐掩盖活性喹诺酮化合物苦味的药剂。但是，为了制备这些药剂，首先要制备喹诺酮羧酸的扑酸盐，然后分离、纯化，随后制剂化。
发明内容 已经发现喹诺酮羧酸或萘啶酮羧酸的口服制剂可以通过以下方法制得：在有赋形剂、有或无辅助剂的情况下，将喹诺酮羧酸或萘啶酮羧酸或其水溶性盐或衍生物(优选其水性盐溶液)与扑酸或其水溶性盐或衍生物(优选其水性盐溶液)混合，使用干燥的混合物时在水中混合，并任选地将所得的混合物进一步转化为适于使用的形式。
按照本发明的方法生产的喹诺酮羧酸或萘啶酮羧酸制剂可以毫无问题的口服，甚至可以投药给由于其苦味而拒绝服用含有喹诺酮羧酸或萘啶酮羧酸制剂的动物。
制备该制剂时，不必首先制备和分离活性化合物的扑酸盐，然后将这些盐置于赋形剂。令人吃惊的是，对于制备本发明涉及的制剂来说，单独将活性化合物和扑酸或其盐或衍生物混合，或在有水的情况下与赋形剂一起混合，形成制剂就足够了。更令人吃惊的是，该制剂可以毫不犹豫地口服，甚至是味觉灵敏的动物。由于不清楚按照本发明的方法是否完全、部分或一点也没有形成扑酸盐，因此这一点是人们预期不到的。但可以确定的是制成了一种在口服时很易接受的制剂，该制剂含有以下成分：
-赋形剂，
-喹诺酮羧酸或萘啶酮羧酸，其盐或其衍生物，
-扑酸，其盐或其衍生物。
喹诺酮羧酸或萘啶酮羧酸及其水溶性盐和衍生物是已知的，例如参见EP-A350950，302372，49355，47005，242789，259804，215650，131839，109284；DE-A2804097；FR-A2463771；PCT WO 92/9596。(在这些出版物中提到的制剂和特定的化合物一同并入本文作为参考。)
优选的化合物是：替马氟沙星、托舒沙星、恩氟沙星、环丙沙星、氧氟沙星、奥比沙星、马波沙星、诺氟沙星、benofloxacin、宾氟沙星、达氟沙星、双氟哌酸、沙氟沙星、premafloxacin、依巴沙星。
特别优选的化合物是：恩氟沙星、达氟沙星、沙氟沙星。
这些活性化合物的衍生物包括它们的酯，如C1-C4烷基酯。
这些活性化合物的盐包括与酸形成的所有生理上可接受的盐。这些酸包括氢卤酸、磺酸、羧酸、氨基酸、聚羟基羧酸、磷酸、硝酸、硫酸。特别是甲磺酸、乙磺酸、羟基乙磺酸、苯磺酸、p-甲苯磺酸、甲酸、乙酸、丙酸、二羟甲基丙酸、羟基乙酸、乳酸、羟基马来酸、草酸、琥珀酸、富马酸、马来酸、戊二酸、丙二酸、己二酸、抗坏血酸、苹果酸、柠檬酸、酒石酸、氨基水杨酸、邻氨基苯甲酸、苯甲酸、羟基苯甲酸、苯乙酸、水杨酸、邻苯二甲酸、烟酸、苦杏仁酸、天门冬氨酸、谷氨酸、葡糖酸、葡糖醛酸、乳糖酸、半乳糖醛酸、半乳糖二酸、磷酸、硝酸、盐酸、硫酸、5-氧代四氢呋喃-2-羧酸、2-羟基戊二酸。
最优选的是盐酸或葡糖酸。
扑酸及其盐是已知的，例如参见The Merck Index，第10版，6867。
与扑酸形成盐的合适的碱例如如下：碱金属和碱土金属氢氧化物，如KOH、NaOH、Ca(OH)2，氨，碱基氨基酸如精氨酸、赖氨酸，胆碱，N-甲基葡糖胺，乙二胺，单、双、三烷基胺，取代的胺如二乙醇胺，环状胺如吗啉、哌嗪、氨基三丁醇(＝三(羟甲基)氨基甲烷)。
特别合适的是KOH、精氨酸、赖氨酸、N-甲基葡糖胺。
对于本发明的制剂来说合适的赋形剂是所有的固体惰性物质。
无机的或有机的物质都可以使用。
无机物质的例子有：食盐、碳酸盐(例如碳酸钙)、碳酸氢盐、氧化铝类、硅酸、粘土、沉淀的或胶体的二氧化硅、磷酸盐。
有机物质的例子有：糖、纤维素、任选的其衍生物、淀粉(例如玉米、稻、马铃薯、木薯或小麦淀粉)、食品和饲料例如奶粉、兽肉、磨过的和研碎的谷粒。
使用的载体也可以是上述物质的混合物。
还具有能结合水的特性的其它载体是例如羧甲基纤维素、甲基纤维素和其它纤维素以及淀粉衍生物、聚丙烯酸酯、藻酸盐、明胶、甲壳质、***胶、聚乙烯吡咯烷酮、聚乙烯醇、乙烯醚和酸酐的共聚物、聚乙二醇、蜡、胶体二氧化硅或这些物质以及同类物质的混合物。
为了制备本发明的制剂，还可以加入其它辅助剂如防腐剂、抗氧剂、光稳定剂、着色剂、吸收促进剂、崩解促进剂、粘合剂或润滑剂及稳定剂。
合适的防腐剂例如苯甲醇、苯甲酸、p-羟基苯甲酸、丙酸及其衍生物和盐以及山梨酸及其衍生物和盐。
合适的抗氧剂例如白蛋白、氨基酸、抗坏血酸、它们的盐和衍生物；丁羟基苯甲醚；丁羟基甲苯；对苯二酚衍生物。
合适的光稳定剂例如芳香族衍生物、具有合适的吸收波长的化合物。
合适的着色剂例如色料(如铁颜料)、水溶性着色剂或可溶于有机溶剂的着色剂。
合适的吸收促进剂例如脂肪酸、脂肪酸酯及其混合物、脂肪醇、卵磷脂、胆汁酸盐。
合适的稳定剂例如亚硫酸钠、EDTA及其盐。
合适的润滑剂例如硬脂酸镁、硬脂酸、滑石粉、膨润土；合适的崩解促进剂例如淀粉或交联聚乙烯吡咯烷酮；合适的粘合剂例如淀粉、明胶或线形聚乙烯吡咯烷酮，还有干燥的粘合剂如微晶纤维素。
本发明的方法是通过在水存在下将各种成分混合实现的。其成分加入的顺序并不是很重要的。
因此，例如，赋形剂和辅助剂成分可以首先加入一个常规的混合器中并混合。在该混合物中加入活性化合物或其水溶性盐或衍生物，优选水性盐溶液，并混合。由此得到的混合物再与扑酸或其水溶性盐或衍生物混合，优选其水性盐溶液，当使用的是干燥混合物时在水中混合。
为了制备水溶液，加入水溶性的溶剂和辅助剂是有益的。
这些添加剂的例子包括：丙二醇、乙醇、异丙醇、丙酮、N-甲基吡咯烷酮、2-吡咯烷酮、氯丁醇、苯甲醇，防腐剂、稳定剂如亚硫酸钠、Na-EDTA，着色剂、增稠剂如聚乙烯吡咯烷酮、纤维素衍生物、明胶、淀粉糊精。
活性化合物(盐)溶液的浓度是0.5至50％；优选10至40％。
扑酸(盐)溶液的浓度是0.5至40％；优选5至30％。
在按照本发明的方法制备的产品中活性化合物对扑酸的比率为当使用1mol活性成分时扑酸为0.5至5mol，优选0.7至2mol，最优选1mol。
所述各种成分可以在任何类型的混合器中混合。例如具有切碎装置的高强度混合器特别适于制备均质混合物。所使用的溶液或水可以按任意顺序加入到干燥的混合物中，包括通过倾倒、浇注、喷雾或雾化方式交替地、连续地或分批地加入。
制得的湿混合物进一步加工并例如磨碎，干燥，然后过筛或研磨。
同样地，使用流化床的造粒方法是一个合适的制备方法。为此目的，例如使用一个或多个喷嘴将溶液喷在流动的混合物上，并如果需要可以在此过程中干燥。
如果需要细小的粒子，可以进行微粉化(例如使用气体撞击、砂磨机或研磨机)。
本发明制备的制剂可以加入其它赋形剂，在食品应用中它们可以是单一的一种食物或其混合物。该制剂可以以粉末的形式干或湿挤出或造粒。
本发明的制剂可以干涂于食物颗粒上。加入粘合剂是有益的。合适的粘合剂是例如植物油、动物油或合成油、脂肪、脂肪酸、脂肪醇、蜡、明胶。
按照本发明制备的制剂也可以混入到润湿的颗粒中。这种颗粒可以包含动物物质(例如润湿的颗粒)。
特别是，按照本发明制备的制剂也可以被封入胶囊，囊壁由硬的或软的明胶构成。如果合适，该胶囊还可以是肠溶衣的。
按照本发明制备的制剂还可以用于制造其它的口服制剂，如：
-口服液，稀释后供口服的浓缩物；
-口服的乳剂和悬浮液；
-糊剂或其中制剂在半固体基质或水包油或油包水型乳剂基质中加工的制备物；
-固体制剂如粉剂、预混物或浓缩物、小丸剂、挤出物、片剂、大丸剂、胶囊剂；
-或所述剂型的组合。
按照本发明制备的制剂可以使用其本身，或使用适于预防或治疗人或动物的疾病，特别是治疗细菌感染的制剂。
它们特别适用于老年病学和小儿科领域或兽医实践中味觉灵敏的动物，例如猫、猪或鱼。
该制剂具有防止病原微生物侵入人体或动物体的活性。
这些微生物包括：
1.螺旋体科(例如密螺旋体属、钩端螺旋体属、疏螺旋体属)
2.spirillaceae
3.细球菌科(例如生物属型为A-F的葡萄球菌、St.hyicus)
4.链球菌科(例如***链球菌、马链球菌、无乳链球菌、停乳链球菌、链球菌沉淀反应组为A-N的链球菌)
5.假单胞菌科(例如鼻疽假单胞菌、洋葱假单胞菌、绿脓假单胞菌、嗜麦芽假单胞菌，布鲁氏杆菌属如流产布鲁氏杆菌、马尔他布鲁氏杆菌、猪布鲁氏杆菌，博代氏杆菌属如支气管败血性博代氏杆菌、摩拉克氏菌属、不动杆菌属)
6.肠杆菌科(例如B-E型沙门氏菌属、志贺氏菌属、大肠杆菌、克雷白氏杆菌属、变形杆菌属、柠檬酸杆菌属、爱德华氏菌属、嗜血杆菌属、普罗威登斯菌属、耶尔森氏菌属)
7.vibronaceae(例如弧菌属如霍乱弧菌)、巴斯德氏菌属如出血败血性巴斯德氏菌、气单胞菌属、放线杆菌属、链杆菌属)
8.拟杆菌类(例如拟杆菌、梭形杆菌属)
9.erysippelathrix，李司忒氏菌属例如单核细胞增多性李司忒氏菌)
10.芽胞杆菌科(例如芽胞杆菌属、A-D型梭状芽胞杆菌、如产气荚膜梭状芽胞杆菌、乳酸杆菌属和厌氧球菌，如消化链球菌属、消化球菌属)
11.coryneform菌(例如化脓棒状杆菌)
12.分支杆菌科(例如牛结核分支杆菌、鸟结核分支杆菌、结核分支杆菌)
13.放线菌科(例如牛放线菌、伊氏放线菌)
14.诺卡氏菌科(例如皮疽诺卡氏菌、星形诺卡氏菌)
15.立克次氏体科(例如柯克斯氏立克次氏体属、立克次氏体)
16.巴尔通氏体科(例如巴尔通氏体属)
17.衣原体科(例如鹦鹉热衣原体)
18.枝原体科(霉状枝原体、无乳枝原体、鸡败血枝原体)
人和动物的病原微生物感染下述单个或多个动物器官***可以导致疾病的征兆：
肺和气管内腔；消化***如胃、肠；胸和***；生殖***如子宫；软组织如皮肤、肌肉；指甲、爪、蹄；主动或被动的运动***如骨、肌肉、腱、关节；泌尿***如肾、尿道、输尿管；神经***如耳、眼、鳃。
如上所述，该制剂用于治疗人或动物的细菌性疾病。这些动物包括：
哺乳动物如牛、马、猪、绵羊、山羊、狗、猫、骆驼，毛皮动物如貂、灰鼠，动物园动物和实验室动物如小鼠和大鼠；
鸟如鹅、小鸡、火鸡、鸭、鸽，饲养场鸟，实验室鸟如鹦鹉、虎皮鹦鹉；
鱼，尤其是经济有用的鱼，例如鲤鱼、鲑鱼、***哈鱼、鲤鱼类淡水鱼、鳗鱼、黄尾鱼、sea bass、鲷科海鱼，此外还有观赏用鱼和池塘养鱼；
爬行动物如鳄鱼、蛇、蛙；
甲壳纲动物例如对虾属；如P.monodon、蟹、龙虾。
动物的细菌性疾病包括猪痢疾，鸟螺旋体病，牛、猪、马、狗钩端螺旋体病；弯曲杆菌引起的牛肠炎；弯曲杆菌引起的绵羊和猪流产；弯曲杆菌感染皮肤引起的鸡肝炎；狗脓皮病、外耳炎；牛、绵羊、山羊乳腺炎；链球菌感染马、猪和其它类型动物引起的链球菌乳腺炎；小牛和其它类型动物的肺炎球菌感染；马鼻疽；结膜炎；肠炎；肺炎；牛、绵羊、猪布鲁氏菌病；猪atropic鼻炎；牛、马、绵羊、鸡和其它类型动物的沙门氏菌病；败血病；猪仔的大肠杆菌感染；子宫炎-乳腺炎-无乳-(MMA)-综合症状；克雷白氏杆菌属感染；假结核病；接触传染的胸膜肺炎；初期巴斯德氏菌病；驹共济失调；牛和宠物的坏死杆菌病；钩端螺旋体病；猪和其它类型动物的丹毒；李司忒氏菌病；炭疽；梭状芽胞杆菌病；破伤风感染；肉毒中毒；化脓棒状杆菌
感染；牛、猪、鸟和其它类型动物的肺结核；反刍动物的类结核；诺
卡氏放线菌病；Q热；鸟疫-鹦鹉热；脑脊髓炎；牛和其它动物的支
原体病；猪的地方性兽病肺炎。
鱼的细菌性疾病包括：
细菌性肾疾病(由沙氏肾杆菌引起)；链球菌病；假单胞菌属感
染如荧光假单胞菌、病鳝假单胞菌；爱德华氏菌属感染，例如迟钝爱
德华氏菌；气单胞菌属感染，例如杀鲑气单胞菌(疖病)，嗜水气单
胞菌；弧菌病，例如鳗弧菌，杀鲑弧菌，副溶血弧菌；bacillus
culumnaris；立克次氏体病，例如SRS。
甲壳纲动物的细菌性感染包括：
弧菌病，例如副溶血弧菌，解藻朊酸弧菌；假单胞菌属感染，例
如假单胞菌属。
具体实施方式按照本发明的方法提供如下制剂：
实施例1
| 恩氟沙星∶扑酸摩尔比 | 颗粒a1∶1 | 颗粒b1∶0.9 | 颗粒c1∶1 | 颗粒d1∶1.5 |
| 恩氟沙星 | 10.00 | 10.00 | 2.500 | 2.500 |
| 葡萄糖酸内酯 | 6.00 | 6.00 | 1.500 | - |
| 甲磺酸 | - | - | - | 0.670 |
| 亚硫酸钠 | 0.10 | 0.10 | 0.025 | 0.025 |
| 扑酸 | 10.82 | 9.74 | 2.705 | 4.057 |
| 甲基葡糖胺 | 10.88 | - | 2.720 | 4.080 |
| 精氨酸 | - | 8.75 | - | - |
| MHP-纤维素50 | - | - | 1.500 | 1.500 |
| Ac-Di-Sol | 7.00 | 7.00 | - | - |
| 润湿玉米淀粉加到(重量单元g) | 100.0 | 100.0 | 100.0 | 100.0 |
将赋形剂和辅助剂装入混合-造粒机中并混合。然后将恩氟沙星-葡萄糖酸内酯-或甲磺酸盐的水溶液加入到最初装入的混合物中。随后，将扑酸-精氨酸-或甲基葡糖胺盐的水溶液加入到所形成的混合物中。然后将混合物置于合适的装置中干燥(例如流化床干燥器)并过筛(例如振动筛)。
按照实施例1的方法得到的制剂可以使用其本身，也可以在研磨后或进一步加工后得到如下组成的制剂。实施例2 15mg片
实施例3 40mg片
实施例4 恩氟沙星在水中的悬浮液2.5％
实施例5 恩氟沙星在油中的悬浮液2.5％
实施例6 恩氟沙星糊剂2.5％
实施例7 恩氟沙星凝胶2.5％
实施例8 含药食品0.05％
| ％ | mg/片 | |
| 恩氟沙星颗粒10％ | 75.00 | 150.00 |
| 玉米淀粉 | 15.00 | 30.0 |
| 微晶纤维素 | 9.55 | 19.1 |
| 硬酯酸镁 | 0.30 | 0.6 |
| 胶体二氧化硅 | 0.15 | 0.3 |
| 200.0 |
| ％ | mg/片 | |
| 恩氟沙星颗粒10％ | 80.00 | 400.00 |
| 玉米淀粉 | 10.00 | 50.00 |
| 微晶纤维素 | 9.55 | 47.75 |
| 硬酯酸镁 | 0.30 | 1.50 |
| 胶体二氧化硅 | 0.15 | 0.75 |
| 500.0 |
| 恩氟沙星颗粒10％ | 25.00g |
| 苯甲醇羧甲基纤维素钠 | 1.40g0.50g |
| 软化水 | 到100ml |
| 恩氟沙星颗粒10％ | 25.00g |
| 苯甲醇 | 1.40g |
| 中链甘油三酯 | 到100ml |
| 恩氟沙星颗粒10％ | 25.00g |
| 脂肪醇 | 5.00g |
| 白凡士林 | 10.00g |
| 粘性石腊 | 60.00g |
| 100.00g |
| 恩氟沙星颗粒10％ | 25.00g |
| 1，2-丙二醇 | 10.00g |
| 苯甲醇 | 1.40g |
| 羧甲基纤维素钠 | 2.50g |
| 软化水 | 61.10g |
| 100.00g |
| 恩氟沙星颗粒10％ | 0.5g |
| 食物混合物/小丸 | 99.5g |
| 100.00g |
Claims (3)
1.一种制备喹诺酮羧酸或萘啶酮羧酸口服制剂的方法，其特征在于，在有赋形剂、有或无辅助剂的情况下，将喹诺酮羧酸或萘啶酮羧酸或其水溶性盐或衍生物或其水性盐溶液与扑酸或其水溶性盐或衍生物或其水性盐溶液混合，使用干燥的混合物时在水中混合，并任选地将所得的混合物进一步转化为适于使用的形式。
2.一种通过以任意顺序将以下成分与任选存在的辅助剂混合制得的颗粒状产品：
-赋形剂，
-喹诺酮羧酸或萘啶酮羧酸或其水溶性盐或衍生物，
-扑酸或其水溶性盐或衍生物，
-水，
其特征在于，所述颗粒状产品能通过权利要求1的方法而得到。
3.根据权利要求2的组合物，其特征在于，活性化合物为恩氟沙星的水溶性盐。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19633480.2 | 1996-08-20 | ||
| DE19633480A DE19633480A1 (de) | 1996-08-20 | 1996-08-20 | Oral applizierbare Formulierungen von Chinolon- und Naphthyridoncarbonsäuren |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1228023A CN1228023A (zh) | 1999-09-08 |
| CN1113651C true CN1113651C (zh) | 2003-07-09 |
Family
ID=7803084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97197362A Expired - Fee Related CN1113651C (zh) | 1996-08-20 | 1997-08-07 | 喹诺酮羧酸或萘啶酮羧酸的口服制剂 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5808076A (zh) |
| EP (1) | EP0920317B1 (zh) |
| JP (1) | JP4338222B2 (zh) |
| KR (1) | KR100493577B1 (zh) |
| CN (1) | CN1113651C (zh) |
| AR (1) | AR008304A1 (zh) |
| AT (1) | ATE260657T1 (zh) |
| AU (1) | AU3942797A (zh) |
| BR (1) | BR9711338B1 (zh) |
| CA (1) | CA2263584C (zh) |
| DE (2) | DE19633480A1 (zh) |
| DK (1) | DK0920317T3 (zh) |
| ES (1) | ES2213829T3 (zh) |
| HK (1) | HK1022435A1 (zh) |
| MY (1) | MY117606A (zh) |
| TW (1) | TW518226B (zh) |
| WO (1) | WO1998007428A1 (zh) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100365679B1 (ko) * | 2000-04-03 | 2002-12-26 | 주식회사 엘지생명과학 | 기호성이 우수한 엔로프록사신 프리믹스 조성물 및 그제조방법 |
| US6518252B2 (en) * | 2000-09-20 | 2003-02-11 | University Of Georgia Research Foundation, Inc. | Method of treating aquatic animals with an antimicrobial agent and chelating agent |
| US20020122824A1 (en) * | 2001-01-24 | 2002-09-05 | Francisco Cabrera | Solid phase dispersion of quinolone-or naphthyridonecarboxylic acids |
| US6589955B2 (en) | 2001-06-20 | 2003-07-08 | Bristol-Myers Squibb Company | Pediatric formulation of gatifloxacin |
| WO2003031443A1 (en) * | 2001-10-04 | 2003-04-17 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Dual actions antibiotics comprising a oxazoldinone and a quinolone or naphthyridinone moiety |
| DE502004011696D1 (de) * | 2003-02-10 | 2010-11-11 | Bayer Schering Pharma Ag | Behandlung bakterieller erkrankungen der atmungsorgane durch lokale applikation von fluorchinolonen |
| DE602004014361D1 (de) | 2003-04-30 | 2008-07-24 | Morphochem Ag Komb Chemie | Verwendung von oxazolidinon-chinolin-hybrid-antibiotika zur behandlung von anthrax und anderen infektionen |
| DE10328666A1 (de) * | 2003-06-26 | 2005-01-13 | Bayer Healthcare Ag | Tabletten enthaltend Geschmacks-und/oder Aromastoffe |
| DE10337191A1 (de) * | 2003-08-13 | 2005-03-17 | Bayer Healthcare Ag | Neue Verwendung von Chinolon-Antibiotika |
| DE10340485B4 (de) * | 2003-09-03 | 2015-05-13 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Verfahren zur Herstellung von Oxazolidinon-Chinolon Hybriden |
| DE10351448A1 (de) * | 2003-11-04 | 2005-06-09 | Bayer Healthcare Ag | Geschmackstoffhaltige Arzneimittelformulierungen mit verbesserten pharmazeutischen Eigenschaften |
| US8158797B2 (en) * | 2003-12-18 | 2012-04-17 | Morphochem Aktiengesellschaft Fur Kombinatorische Chemie | Oxazolidinone-quinolone hybrid antibiotics |
| ATE401326T1 (de) | 2003-12-18 | 2008-08-15 | Morphochem Ag Komb Chemie | Oxazolidinon-chinolon hybrid antibiotika |
| CN100360131C (zh) * | 2006-01-24 | 2008-01-09 | 新昌国邦化学工业有限公司 | 一种掩味恩诺沙星的生产方法 |
| FR2896416B1 (fr) * | 2006-01-24 | 2010-08-13 | Vetoquinol | Composition anti-infectieuse comprenant un compose de type pyrido (3,2,1-ij)-benzoxadiazine |
| KR101148501B1 (ko) * | 2007-06-08 | 2012-05-25 | 광동 하이나팜 파마슈티칼 씨오., 엘티디. | 엔로플록사신 미세캡슐 제형 및 그 제조 방법 |
| EP2343089A4 (en) | 2008-09-23 | 2013-05-01 | Jaer S A Lab | USE OF XYLITOL OR DERIVATIVES THEREOF FOR MASKING THE TASTE OF CHEMOTHERAPEUTIC MEDICAMENTS OF THE CHINOLO-N-NAPHTHYRIDONE-CARBOXYLIC ACID GROUP FOR PIG DICULTINATION |
| CA2909111A1 (en) * | 2013-04-09 | 2014-10-16 | Cresset Biomolecular Discovery Ltd | The local treatment of inflammatory ophthalmic diseases |
| CN103251552B (zh) * | 2013-05-30 | 2014-12-31 | 成都乾坤动物药业有限公司 | 一种恩诺沙星糊剂及其制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5232919A (en) * | 1987-11-13 | 1993-08-03 | Asta Pharma Aktiengesellschaft | Azelastine embonate and compositions which contain it |
| US5281596A (en) * | 1986-02-19 | 1994-01-25 | Bayer Aktiengesellschaft | Antibacterial drugs for fish |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL266216A (zh) * | 1960-07-12 | |||
| GB1174221A (en) * | 1968-01-08 | 1969-12-17 | Ici Ltd | Acid-addition Salts of Tetramisole |
| CH524372A (de) * | 1969-01-29 | 1972-06-30 | Ciba Geigy Ag | Verfahren zur Herstellung von stabilen Elixieren, welche therapeutisch verwendbare tricyclische basische Wirkstoffe in Form ihrer Mononatriumpamoate enthalten |
| DE3525335A1 (de) * | 1985-07-16 | 1987-01-22 | Bayer Ag | Embonate von chinoloncarbonsaeuren und ihren derivaten |
| JPS62192321A (ja) * | 1986-02-19 | 1987-08-22 | Bayer Japan Kk | 魚類用抗菌剤 |
| DE3719764A1 (de) * | 1987-06-13 | 1988-12-22 | Bayer Ag | Ionenaustauscherharze beladen mit chinoloncarbonsaeurederivaten, ihre herstellung und verwendung |
| DE4032560A1 (de) * | 1990-10-13 | 1992-04-16 | Bayer Ag | 7-(2,7-diazabicyclo(3.3.0)octyl)-3-chinolon- und -naphtyridoncarbonsaeure-derivate |
-
1996
- 1996-08-20 DE DE19633480A patent/DE19633480A1/de not_active Withdrawn
- 1996-12-06 US US08/761,687 patent/US5808076A/en not_active Expired - Lifetime
-
1997
- 1997-08-07 CA CA002263584A patent/CA2263584C/en not_active Expired - Fee Related
- 1997-08-07 KR KR10-1999-7000990A patent/KR100493577B1/ko not_active IP Right Cessation
- 1997-08-07 AT AT97936690T patent/ATE260657T1/de not_active IP Right Cessation
- 1997-08-07 DE DE59711379T patent/DE59711379D1/de not_active Expired - Lifetime
- 1997-08-07 ES ES97936690T patent/ES2213829T3/es not_active Expired - Lifetime
- 1997-08-07 BR BRPI9711338-7A patent/BR9711338B1/pt not_active IP Right Cessation
- 1997-08-07 DK DK97936690T patent/DK0920317T3/da active
- 1997-08-07 CN CN97197362A patent/CN1113651C/zh not_active Expired - Fee Related
- 1997-08-07 WO PCT/EP1997/004302 patent/WO1998007428A1/de active IP Right Grant
- 1997-08-07 AU AU39427/97A patent/AU3942797A/en not_active Abandoned
- 1997-08-07 JP JP51033898A patent/JP4338222B2/ja not_active Expired - Fee Related
- 1997-08-07 EP EP97936690A patent/EP0920317B1/de not_active Expired - Lifetime
- 1997-08-11 MY MYPI97003670A patent/MY117606A/en unknown
- 1997-08-15 TW TW086111729A patent/TW518226B/zh not_active IP Right Cessation
- 1997-08-19 AR ARP970103769A patent/AR008304A1/es active IP Right Grant
-
2000
- 2000-03-08 HK HK00101449A patent/HK1022435A1/xx not_active IP Right Cessation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5281596A (en) * | 1986-02-19 | 1994-01-25 | Bayer Aktiengesellschaft | Antibacterial drugs for fish |
| US5232919A (en) * | 1987-11-13 | 1993-08-03 | Asta Pharma Aktiengesellschaft | Azelastine embonate and compositions which contain it |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1022435A1 (en) | 2000-08-11 |
| DE19633480A1 (de) | 1998-02-26 |
| JP4338222B2 (ja) | 2009-10-07 |
| EP0920317A1 (de) | 1999-06-09 |
| ATE260657T1 (de) | 2004-03-15 |
| US5808076A (en) | 1998-09-15 |
| ES2213829T3 (es) | 2004-09-01 |
| WO1998007428A1 (de) | 1998-02-26 |
| TW518226B (en) | 2003-01-21 |
| KR100493577B1 (ko) | 2005-06-10 |
| BR9711338A (pt) | 1999-08-17 |
| AR008304A1 (es) | 1999-12-29 |
| DK0920317T3 (da) | 2004-07-05 |
| MY117606A (en) | 2004-07-31 |
| JP2000516239A (ja) | 2000-12-05 |
| KR20000068070A (ko) | 2000-11-25 |
| AU3942797A (en) | 1998-03-06 |
| EP0920317B1 (de) | 2004-03-03 |
| CA2263584C (en) | 2008-12-23 |
| CN1228023A (zh) | 1999-09-08 |
| CA2263584A1 (en) | 1998-02-26 |
| BR9711338B1 (pt) | 2009-01-13 |
| DE59711379D1 (de) | 2004-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1113651C (zh) | 喹诺酮羧酸或萘啶酮羧酸的口服制剂 | |
| CN1213754C (zh) | β－咔啉药物组合物 | |
| EP2063869B1 (en) | Soft chewable veterinary antibiotic formulations | |
| JPS6222716A (ja) | 獣医学の分野に使用する殺バクテリア調製物 | |
| JP2014114310A (ja) | 味のマスキングが改善された押出物 | |
| JP2006503806A (ja) | 活性物質を担持するイオン交換樹脂および増粘剤として本質的に粘性のあるゲル化剤を含む経口医薬製剤 | |
| NO338438B1 (no) | Tabletter inneholdende enrofloksacin og smaks- og/eller aromastoffer og fremgangsmåte for fremstilling derav. | |
| CA2435414C (en) | Solid phase dispersion of quinolone- or naphthyridonecarboxylic acids | |
| CN1823804A (zh) | 一种克拉霉素速释微丸及其制备方法 | |
| WO2013000093A1 (en) | Location-specific bacterial management | |
| CN104161761B (zh) | 一种复方土霉素注射液及其制备方法 | |
| CN1843330A (zh) | 一种含氨基糖苷类抗菌素的缓释剂及其应用 | |
| JP3136516B2 (ja) | 消化管粘膜付着性抗ヘリコバクター・ピロリ組成物 | |
| CN106924198A (zh) | 畜禽用盐酸多西环素口腔崩解片及其制备方法 | |
| CN107445977A (zh) | 一种水溶性马波沙星及其制备方法与应用 | |
| JPH0772177B2 (ja) | キノロンカルボン酸類のエンボネート類 | |
| JP4287948B2 (ja) | 消化管粘膜付着性抗ヘリコバクター・ピロリ組成物 | |
| JPH0683641B2 (ja) | 反芻動物用飼料添加組成物 | |
| CN1845738A (zh) | 适于兽医和医疗应用的组合物 | |
| CN116998603A (zh) | 一种高效小分子有机酸化剂及其制备方法 |
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: BAYER ANIMAL HEALTH PROMOTION CO.,LTD. Free format text: FORMER OWNER: BAYER AG Effective date: 20091106 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20091106 Address after: Germany Leverkusen Patentee after: Bayer Animal Health GmbH Address before: Germany Leverkusen Patentee before: Bayer Aktiengesellschaft |
|
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20030709 Termination date: 20100807 |