WO2010069493A1 - Combinaison améliorée de principes actifs contenant un antibiotique et un médicament anti-inflammatoire non stéroïdien (nsaid) - Google Patents
Combinaison améliorée de principes actifs contenant un antibiotique et un médicament anti-inflammatoire non stéroïdien (nsaid) Download PDFInfo
- Publication number
- WO2010069493A1 WO2010069493A1 PCT/EP2009/008734 EP2009008734W WO2010069493A1 WO 2010069493 A1 WO2010069493 A1 WO 2010069493A1 EP 2009008734 W EP2009008734 W EP 2009008734W WO 2010069493 A1 WO2010069493 A1 WO 2010069493A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- salts
- inflammatory
- antibiotic
- compounds
- Prior art date
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 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
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- FHFYDNQZQSQIAI-UHFFFAOYSA-N pefloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 FHFYDNQZQSQIAI-UHFFFAOYSA-N 0.000 description 1
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- 150000002989 phenols Chemical class 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
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003007 phosphonic acid derivatives Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960000851 pirprofen Drugs 0.000 description 1
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 description 1
- 229920001987 poloxamine Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
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- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- 150000005599 propionic acid derivatives Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 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
- 239000002516 radical scavenger Substances 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 229950007734 sarafloxacin Drugs 0.000 description 1
- 229960005480 sodium caprylate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
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- JNYAEWCLZODPBN-CTQIIAAMSA-N sorbitan Polymers OCC(O)C1OCC(O)[C@@H]1O JNYAEWCLZODPBN-CTQIIAAMSA-N 0.000 description 1
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- 229960004954 sparfloxacin Drugs 0.000 description 1
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
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- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- 229950010392 toldimfos Drugs 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229950008187 tosufloxacin Drugs 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 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
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
Definitions
- the invention relates to novel combination formulations in veterinary medicine containing a quinolone antibiotic and a non-steroidal anti-inflammatory drug (NSAID).
- NSAID non-steroidal anti-inflammatory drug
- the formulations in particular injection solutions containing a quinolone antibiotic and an anti-inflammatory substance are particularly suitable for the parenteral treatment of bacterial infections in animals such. Cattle, pigs, dogs, cats.
- BTD bovine respiratory disease
- Losses are caused by decreased daily gains, reduced fertility, and increased mortality, along with not inconsiderable treatment costs.
- Manheimia haemolytica, Pasteurella multocida and Haemophilus somnis play a role in the pathogenesis of FRG as causative germs.
- Comparable to BRD in cattle are the bacterial infections of the respiratory tract of the pig (SRD, swine respiratory disease), caused by e.g. P. multocida, H. parasuis, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae, Streptococcus suis, Salmonella cholerasuis and mycoplasma.
- SRD swine respiratory disease
- the disease is characterized in both species by a pronounced inflammatory process, which can lead to irreparable lung damage.
- the treatment should therefore both eliminate the causal bacterial pathogens and minimize the inflammatory process.
- the standard therapy so far includes the use of a suitable antibiotic, such.
- enrofloxacin As enrofloxacin (Baytril ®), and in serious clinical diseases beyond the use of NSAIDs such.
- Comparable therapy is also performed in the presence of acute bovine mastitis, metritis, or pork mastitis metritis agalactia, as these bacterial infections are all associated with severe inflammatory processes and are life-threatening to the affected animals.
- the invention relates to a combination comprising a quinolone antibiotic and a non-steroidal anti-inflammatory agent.
- the invention further relates to medicaments containing this combination and the preparation of these medicaments.
- Quinolone antibiotics are antibiotic quinolones, preferably fluoroquinolones; These include, but are not limited to, compounds disclosed in the following documents: US 4,670,444 (Bayer AG), US 4,472,405 (Riker Labs), US 4,730,000 (Abbott), US 4,861,779
- a preferred group of fluoroquinolones are those of the formula (I) or (I-):
- X is hydrogen, halogen, C 1-4 -alkyl, C M -alkoxy, NH 2 , Y stands for radicals of the structures
- R 4 is optionally substituted by hydroxy or methoxy straight or branched Q-Gi-alkyl, cyclopropyl, acyl having 1 to 3 carbon atoms
- R 5 is hydrogen, methyl, phenyl, thienyl or pyridyl
- R 6 is hydrogen or C M is alkyl
- R 7 is hydrogen or 0 ,. 4- alkyl
- R 8 is hydrogen or Q -4 -alkyl
- R 1 is an alkyl radical having 1 to 3 carbon atoms, cyclopropyl, 2-fluoroethyl, methoxy, 4-
- R 2 is hydrogen or alkyl optionally substituted by methoxy or 2-methoxyethoxy having 1 to 6 carbon atoms and cyclohexyl, benzyl, 2-oxopropyl, phenacyl, ethoxycarbonylmethyl, pivaloyloxymethyl
- R 3 is hydrogen , Methyl or ethyl is and
- the compounds of formulas (I) and (II) may be in the form of their racemates or in enantiomers
- Shapes are present.
- R 2 represents hydrogen or Ci -4 -alkyl group
- R 4 stands for optionally hydroxyl-substituted straight-chain or branched C 1 -C 3 -alkyl, oxalkyl having 1 to 4 C atoms
- R 5 is hydrogen, methyl or phenyl
- R 7 is hydrogen or methyl
- R 6 and R 8 are hydrogen and their pharmaceutically usable hydrates, salts and complex compounds.
- R 1 is cyclopropyl
- R 2 is hydrogen, methyl or ethyl
- Y is radicals of the structures
- R 4 is methyl, optionally hydroxy-substituted ethyl, R 5 is hydrogen or methyl,
- R 7 is hydrogen or methyl
- R 6 and R 8 are hydrogen and their pharmaceutically acceptable salts, hydrates and complex compounds.
- Suitable salts are pharmaceutically usable acid addition salts and basic salts.
- Examples of pharmaceutically usable salts are the salts of hydrochloric acid, sulfuric acid, acetic acid, glycolic acid, lactic acid, succinic acid, citric acid, tartaric acid, methanesulfonic acid, 4-toluenesulfonic acid, galacturonic acid, gluconic acid, embonic acid, glutamic acid or aspartic acid.
- the compounds according to the invention can be bound to acidic or basic ion exchangers.
- Suitable pharmaceutically usable basic salts are the alkali metal salts, for example the sodium or potassium salts, the alkaline earth metal salts, for example the magnesium or calcium salts; the zinc salts, the silver salts and the guanidinium salts.
- basic organic compounds can be used to salt with quinolones, for example, ammonia or mono-, di-, trialkylamines and their derivatives such as triethylamine, triethanolamine, 2-aminoethanol, N-methylglucamine (meglumine), cyclic amines such as Morpholine, piperazine or too basic amino acids, especially arginine, lysine, or their decarboxylation products, such as cholamine.
- quinolones for example, ammonia or mono-, di-, trialkylamines and their derivatives such as triethylamine, triethanolamine, 2-aminoethanol, N-methylglucamine (meglumine), cyclic amines such as Morpholine, piperazine or too basic amino acids, especially arginine, lysine, or their decarboxylation products, such as cholamine.
- Hydrates are understood as meaning both the hydrates of the fluoroquinolones themselves and the hydrates of their salts.
- Complex compounds are understood to mean, in particular, the compounds in which the quinolone is bonded to the coordination sphere via the carbonyl, carboxyl or, if appropriate, an amine function or via the cyano group with two or three positively charged metal ions or transition metal ions and ions of the boron. These complexes can be mononuclear or polynuclear.
- fluoroquinolones which may be mentioned are the compounds described in WO 97/31001, in particular 8-cyano-1-cyclopropyl-7 - ((1S, 6S) -2,8-diazabicyclo [4.3.0] nonan-8-yl) 6-fluoro-l, 4-dihydro-4-oxo-3-quinolinecarboxylic acid (pradofloxacin) having the formula
- Pradofloxacin is preferred in its free form as anhydrate, e.g. In modification B (see WO 00/31076) or as trihydrate (cf., WO 2005/097789).
- quinolone anti-infectives include marbofloxacin, danofloxacin, orbifloxacin, difloxacin and ibafloxacin. Also conceivable is the use of the active ingredient ciprofloxacin otherwise used in human medicine.
- Non-steroidal anti-inflammatory drugs also referred to as non-steroidal anti-inflammatory drugs or NSAIDs, include: salicylic acid derivatives such as salicylic acid, acetylsalicylic acid, diflunisal, salicylsalicylate (salsalate), magnesium salicylate, amides of salicylic acid; Acetic acid derivatives, for example, indomethacin, diclofenac, lonazolac, bromfenac, tolmetin, etodolac, aceclofenac, oxametacin; Propionic acid derivatives, for example ibuprofen, flurbiprofen, ketoprofen, dexketoprofen (an analgesic), naproxen, tiaprofenic acid, suprofen, fenoprofen, carprofen, fenbufen, ketorolac, oxaprozin, loxoprofen, suprofen, in
- Non-steroidal anti-inflammatory drugs and analgesics for the purposes of this invention are also pharmaceutically active metabolites of the abovementioned compounds and their prodrug compounds, for example acetamicin or nabumetone.
- NSAIDs non-acidic antipyretic analgesics
- these compounds should also be regarded as non-steroidal anti-inflammatory agents in a broader sense and can be used accordingly in the combinations according to the invention.
- metamizole is preferred for the combinations according to the invention.
- Preferred NSAIDs for the purposes of this invention are ketoprofen, flunixin and meloxicam.
- ketoprofen is particularly preferred.
- the Na + and K + salts of quinolones and ketoprofen are particularly preferred.
- Optically active substances may be used in the form of their stereoisomers or as a mixture of stereoisomers, e.g. as pure or enriched enantiomers or as racemates.
- the combinations according to the invention and medicaments containing them enable the improved treatment of bacterial infections, especially in animals. They are preferably suitable for the treatment of bacterial infections which are accompanied by inflammation. For example, they are suitable for the treatment of bacterial infections z. B. the respiratory tract, such. B. Germany or SRD in cattle or pigs; bacterial infections of the udder in mammals or bacterial infections of the uterus of animals.
- the serum-kinetic profile of the antibiotic in these formulations surprisingly shows a substantial increase in peak serum concentrations (C m, *) of the quinolone antibiotic compared with the single preparation (z. B. when comparing a Enrofloxacin / ketoprofen formulation with the commercial product Baytril ® in Cattle and pig).
- the expected efficacy of a quinolone is derived from its peak serum concentrations (McKellar QA, Sanchez Bruni SF, Jones DG (2004), Pharmacokinetic / pharmacodynamic relationships of antimicrobial drugs used in veterinary medicine., J. vet. Pharmacol. Therap. 27, 503-514), one can conclude an improved antibacterial efficacy of the combination over the single preparation. This improved efficacy was demonstrated in initial clinical trials (see Tables 1 and 2, Figures 1 and 2).
- quinolone antibiotics and nonsteroidal anti-inflammatory agents are usually in weight ratios (quinolone antibiotic: non-steroidal anti-inflammatory agent) of 100: 1 to 1: 100, preferably 50: 1 to 1:50, particularly preferably 50: 1 to 1: 1, in particular 30: 1 to 1: 1 before.
- the combinations according to the invention per application are usually in dosages of 1 to 100 mg, preferably 2 to 50 mg, more preferably 5 to 30 mg quinolone per kg body weight, and 0.1 to 60 mg, preferably 0.5 to 50 mg , more preferably 2 to 10 mg non-steroidal anti-inflammatory drugs per kg body weight applied.
- High-potency non-steroidal anti-inflammatory agents may preferably be administered in dosages of 0.1 to 20 mg, more preferably 0.2 to 10 mg per kg of body weight.
- Non-steroidal anti-inflammatory drugs with comparatively low potency can preferably be administered in dosages of 10 to 100 mg, more preferably 20 to 70 mg per kg of body weight.
- the combination can be applied once or several times.
- the treatment is preferably as a single dose.
- the treatment duration can be extended to several days. Dose and dosage scheme depend on the type and course of the present bacterial infection and can range from several times a day, several days, once to several times daily over several days in different dosages.
- the combination according to the invention is administered once or several times in dosages of 2 to 50 mg quinolone per kg body weight and 1 to 20 mg nonsteroidal anti-inflammatory drugs per kg body weight.
- the combinations are administered to cattle at doses of 5 to 30 mg / kg of quinolone and 2 to 10 mg / kg of nonsteroidal anti-inflammatory drug; even more suitable are doses of 5 to 20 mg / kg of quinolone and 3 to 7 mg / kg of nonsteroidal anti-inflammatory drug.
- the combination according to the invention is administered once or several times in doses of 2 to 50 mg of quinolone per kg of body weight and of 1 to 20 mg of nonsteroidal anti-inflammatory agent per kg.
- the formulations are administered to swine at a dose of 5 to 30 mg / kg of quinolone and 2 to 10 mg / kg of nonsteroidal anti-inflammatory drug; even more suitable are doses of 5 to 20 mg / kg of quinolone and 3 to 7 mg / kg of nonsteroidal anti-inflammatory drug.
- it is preferably applied by injection, in particular intramuscularly.
- formulations according to the invention may optionally contain further substances, in particular useful for the animal organism, such as builders, minerals or immunostimulating substances.
- Vitamin B 12 As builders may be mentioned, inter alia, vitamins, such. Vitamin B 12 and Vitamin C.
- Immunostimulating substances are, for example, pharmacologically acceptable organic phosphonic acid derivatives with immunostimulating action, such as e.g. Toldimfos and in particular butaphosphane.
- the combination according to the invention is characterized by good compatibility.
- combination in the sense of the invention is understood to mean a dosage form which contains all components (so-called fixed combinations) or a combination pack which contains the components separately from one another
- the two components are each in separate containers, Such separate packaging of the two components in a common primary packaging means is also referred to as a kit.
- the active compounds of the combination according to the invention can be converted in a known manner into the usual pharmaceutical forms (formulations).
- a fixed combination (also known as a "fixed combination”) is preferably suitable.
- "Fixed combination” is understood here to mean those pharmaceutical forms in which the two components are present together in a defined formulation in a defined ratio.
- Such fixed combinations can be realized, for example, as solutions, tablets, dragees, pills, capsules, powders and / or granules.
- the active compounds of the combination according to the invention are particularly suitable for being formulated in a fixed combination, in particular in the form of a liquid dosage form for parenteral administration.
- the medicaments according to the invention are generally suitable for use in humans and animals. Preferably, they are used in livestock and animal breeding in livestock, breeding, zoo and pets, especially in mammals and poultry.
- the livestock and breeding animals include mammals such as e.g. Cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur animals such as e.g. Mink, chinchilla, raccoon, as well as birds such as e.g. Chickens, geese, turkeys, ducks, quails, pigeons and ostriches. Examples of preferred farm animals are beef, sheep, pork, horse, turkey and chicken.
- Hobby animals include dogs, cats, horses, rabbits, rodents such. Golden hamsters, guinea pigs, mice, as well as reptiles, amphibians and birds for home and zoo keeping.
- the medicaments according to the invention are preferably used in farm animals, in particular in cattle and pigs.
- the application can be both prophylactic, metaphylactic and therapeutic. It is usually carried out in the form of suitable preparations parenterally as an injection, for. Intramuscular, intracutaneous, subcutaneous, intravenous, intraperitoneal or oral, e.g. as a tablet, suspension, dragee or through implants. Usually, the application can also be carried out as an ointment or suspension intramammary, as well as intrauterine or rectally as a suppository, tablet or suspension. Furthermore, the dermal application is conceivable.
- Formulations of the invention for parenteral administration can be prepared as a solution, emulsion or suspension.
- Imaging solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly additives such as co-solvents, solubilizers, acids, bases, buffer salts, antioxidants, preservatives, isotonizing agents, absorption promoting substances, dyes, substances that improve the local compatibility, compounds containing the Influencing theological behavior of injection solutions, or adding cryoprotectants.
- the solutions are sterile filtered and bottled.
- the liquid formulation contains physiologically acceptable solvents such as water or water-miscible substances.
- glycerol propylene glycol
- polyethylene glycols compatible alcohols such as ethanol, benzyl alcohol or n-butanol, ethyl lactate, ethyl acetate, triacetin, N-methylpyrrolidone, propylene carbonate, glycofurol , Dimethylacetamide, 2-pyrrolidone, isopropylideneglycerol, or glycerol formal.
- suitable alcohols such as ethanol, benzyl alcohol or n-butanol
- ethyl lactate ethyl acetate
- triacetin N-methylpyrrolidone
- propylene carbonate glycofurol
- Dimethylacetamide Dimethylacetamide
- 2-pyrrolidone isopropylideneglycerol
- glycerol formal glycerol formal.
- Combinations of the solvents are also conceivable. Preference is given to water-based formulations in which other solvent
- the active compounds can also be dissolved in physiologically tolerated vegetable or synthetic oils which are suitable for injection.
- vegetable, animal and synthetic oils such as cottonseed oil, sesame oil, soybean oil, medium chain triglycerides of a chain length of Ci 2 -Ci 8 , propylene glycol such as Propylenglykoloctanoat-decanoate, or paraffin called.
- the formulations according to the invention may also contain co-solvents, preferably when the formulations contain water; the cosolvents can improve the solubility of certain formulation ingredients.
- the cosolvents are usually used in proportions of 1 to 10%, preferably from 3 to 8% (percentages in each case M / V).
- cosolvents examples which may be mentioned as cosolvents are: pharmaceutically acceptable alcohols, dimethyl sulfoxide, ethyl lactate, ethyl acetate, triacetin, N-methylpyrrolidone, propylene carbonate, propylene glycol, glycofurol, dimethylacetamide, 2-pyrrolidone, isopropylideneglycerol, glycerol formal, glycerol and polyethylene glycols.
- Kosolvenz are particularly suitable pharmaceutically acceptable alcohols, such as.
- ethanol benzyl alcohol or n-butanol. Mixtures of the abovementioned solvents can also be used as cosolvents.
- solubilizers may be mentioned: compounds that promote the dissolution of the active ingredient in the main solvent or prevent its precipitation.
- examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters, poloxamers.
- bases are often used in the formulations of this invention.
- inorganic basic compounds such as the hydroxides, carbonates, bicarbonates, sulfites and hydrogen sulfites of the alkali metals, alkaline earth metals and earth metals or basic salts of the transition metals which form water-soluble salts with the quinolones and NSAED compounds.
- the sodium or potassium salts, the alkaline earth salts for example the magnesium or calcium salts; the zinc salts and silver salts.
- basic organic compounds can be used for salt formation such as ammonia or mono-, di-, trialkylamines and their derivatives such as triethylamine, triethanolamine, 2-aminoethanol, N-methylglucamine (meglumine), cyclic amines such as morpholine, piperazine or basic amino acids, in particular arginine , Lysine, or their decarboxylation products, such as cholamine.
- Particularly preferred bases in the sense of the formulations according to the invention are NaOH, KOH or arginine.
- Preservatives may be included in the liquid formulation.
- preservatives which may be mentioned are: Aromatic or aliphatic alcohols such as benzyl alcohol, ethanol, n-butanol, phenol, cresols, chlorobutanol, para-hydroxybenzoic acid esters (in particular the methyl and propyl esters), salts or the free acids of the carboxylic acids such as sorbic acid, benzoic acid , Lactic acid or propionic acid, quaternary ammonium compounds such as benzalkonium chloride, benzethonium chloride or cetylpyridinium chloride, mercury compounds such as thiomersal.
- Dyes are all animal-approved dyes that may be dissolved or suspended, such as carotenoids or certain vitamins, such as vitamin B 12.
- Absorption promoting substances are e.g. DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.
- spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.
- antioxidants for example, sulfites and bisulfites (Na-sulf ⁇ t, Na-metabisulfit), organic sulfur compounds (cystine, cysteine, cysteine hydrochloride, cysteamine, methionine, thioglycerol, thioglycolic acid, thiolactic acid, glutathione) phenols (tocopherols, as well as vitamin E and vitamin E-TPGS (d-alpha-tocopherylpolyethylene glycol-lOOO-succinate)), butylhydroxyanisole, butylhydroxytoluene, octyl- and dodecylgallate), organic acids (ascorbic acid, citric acid, tartaric acid, lactic acid) and their salts and esters.
- organic sulfur compounds cysteine, cysteine hydrochloride, cysteamine, methionine, thioglycerol, thioglycolic acid, thiolactic acid, glutathione
- Synergists of these antioxidants may be: amino acids (eg alanine, arginine, methionine, cysteine), citric acid, tartaric acid, edetic acid or its salts, phosphoric acid derivatives or polyalcohols and polyethers (polyethylene glycol).
- amino acids eg alanine, arginine, methionine, cysteine
- citric acid tartaric acid
- edetic acid or its salts phosphoric acid derivatives or polyalcohols
- polyethers polyethylene glycol
- Sunscreen agents are e.g. Substances from the class of benzophenones or novantisolic acid.
- Viscosity modifiers may be added to modify the fluidity of the injection solutions. They serve to regulate the theological properties or to set a yield point.
- cellulose derivatives such as hydroxypropyl, hydroxyethylmethyl or methylcellulose, gum arabic, carboxymethylcelluloses and their salts, polyacrylic acids and their salts, polyvinyl alcohol, co-polymers polymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, polyvinylpyrrolidone, gelatin, poloxamers, starch, hydroxyethyl starch, dextrans, alginates.
- low molecular weight solvents such as ethanol are used, or glycerol, to increase the viscosity optionally.
- the liquid formulations for injection may contain substances which improve the local tolerance when applied.
- examples include: The above antioxidants or free-radical scavengers such as vitamin E, water-soluble vitamin E esters or vitamin C, sodium disulfide or acetylcysteine.
- Complexing agents such as cyclodextrins (eg hydroxyproyplecyclodextrin), sodium EDTA (sodium salt of ethylenediaminetetraacetic acid), polyvinylpyrrolidone, dexpanthenol, salts of fatty acids such as sodium caprylate, salts of polyvalent metal cations (eg Me 2+ or Me 3+ ), in particular the alkaline earth metals and especially magnesium in its salt forms, amino acids and especially arginine or lysine, poloxamers, poloxamines, cosolvents such as n-butanol, glycerol, polyethylene glycol, propylene glycol or dimethylacetamide, dextrans, creatine, creatinine, acids such as gluconolactonic acid, lactic acid, embonic acid, citric acid, tartaric acid, mucic acid or hyaluronic acid, lecithins containing 70-100% of phosphatidylcholine from soy
- substances may be added for isotonization or freezing point regulation, e.g. may be mentioned: sodium chloride, glycerol, carbohydrates such as sorbitol or glucose.
- the injection solution may also contain pharmaceutically active substances or builders which are oil soluble and therefore in the form of an emulsion.
- Emulsions are either water-in-oil type or oil-in-water type.
- hydrophobic phase may be mentioned: paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid biglyceride, Triglyceride mixture with vegetable fatty acids of chain length Cg. ⁇ 2 or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated, possibly also hydroxyl-containing fatty acids, mono- and diglycerides of Cg / C ⁇ Q fatty acids.
- Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, esters of a medium chain branched fatty acid with saturated fatty alcohols of chain length C ⁇ gC ⁇ g, isopropyl myristate, isopropyl palmitate, caprylic / capric esters of saturated fatty alcohols of chain length C ⁇ 2 -C ⁇ g, isopropyl stearate, oleyl oleate, oleic acid, ethyl oleate, ethyl lactate, waxy fatty acid esters such as dibutyl phthalate, adipic acid adipate, the latter related ester mixtures, inter alia Fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oley
- Fatty acids e.g. Oleic acid and its mixtures.
- hydrophilic phase may be mentioned: water, alcohols such as e.g. Propylene glycol, glycerol, sorbitol and their mixtures.
- Emulsifiers ⁇ including surfactants mention may be made, for example: fatty acid salts, fatty, fatty alkylsulfonates, linear Aklylbenzolsulfonate, ether sulfates Fettalkylpolyethylenglycol-, Fettalkylpolyethylenglycolether, Alkylphenolpolyethylenglycolether, glycosides alkylpolyglycosides, fatty acid N-methlyglucamide, poloxamers, dioctylsulfosuccinate, polyoxiethyltechnisch and not polyoxiethyltechnisch mono- and difatty of glycerol, polyoxyethylated and non-polyoxyethylated monofatty acid esters of propylene glycol, polyoxyethylated and non-polyoxyethylated mono-, di-, triflic acid esters of sorbitol and its mono- and dianhydrides (pol
- Viscosity-increasing and emulsion-stabilizing substances such as carboxymethyl cellulose,
- the injection solution may also contain other pharmaceutically active substances or builders that are not sufficiently oil or water soluble and are therefore present in finely divided, suspended form as a solid.
- Suspensions are prepared by suspending the active ingredient in a carrier liquid optionally with the addition of further auxiliaries, such as wetting agents, dyes, substances which promote absorption, preservatives, antioxidants, light stabilizers.
- auxiliaries such as wetting agents, dyes, substances which promote absorption, preservatives, antioxidants, light stabilizers.
- carrier liquids As carrier liquids, all homogeneous solvents and solvent mixtures may be mentioned.
- Suitable wetting agents are the emulsifiers specified above.
- further stabilizers may be added to prevent crystal growth and aggregation of the suspended particles, for example, lecithins, phosphatidyl cholines, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone,
- Carboxymethylcellulose and its salts methyl, hydroxyethyl, hydroxypropyl and ethylcellulose, gelatin, pectins, sorbitol, dextran, natural and derivatized polysaccharides.
- the combinations according to the invention are formulated as aqueous solutions.
- m / V preferably 0.2 to 8% m / V, more preferably 0.3 to 7% m / V of non-steroidal anti-inflammatory agent.
- m / V preferably 0.5 to 5% m / V, particularly preferably 0.5 to 3% m / V n-butanol.
- aqueous solutions are made alkaline with base, to a pH of 9 to 13, preferably 10.5 to 12.5.
- bases come z. B. in question: basic amino acids, such as.
- arginine or alkali metal hydroxides such as sodium hydroxide or potassium hydroxide. More preferably, potassium hydroxide is used.
- Figure 1 Mean serum concentration-time profile of enrofloxacin (Baytril 10% inj versus combination formulation) after subcutaneous injection in cattle.
- Figure 2 Mean serum concentration-time profile of enrofloxacin (Baytril 10% inj. Versus combination formulation) after intramuscular injection in pigs. formulation Examples
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Abstract
L'invention concerne de nouvelles formulations de combinaisons en médecine vétérinaire qui contiennent un antibiotique du groupe quinolone et un médicament anti-inflammatoire non stéroïdien (NSAID). Les formulations, notamment des solutions d'injection, qui contiennent un antibiotique du groupe quinolone et une substance anti-inflammatoire, conviennent notamment pour le traitement parentéral d'infections bactériennes chez les animaux comme, par exemple, les boeufs, les porcs, les chiens, les chats.
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GB2480276A (en) * | 2010-05-11 | 2011-11-16 | Michael Hilary Burke | Process for the preparation of an aqueous injectable enrofloxacin antimicrobial formulation |
CN110327348A (zh) * | 2019-07-19 | 2019-10-15 | 余祖功 | 含恩诺沙星和美洛昔康的复方长效注射液及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005018641A2 (fr) * | 2003-08-13 | 2005-03-03 | Bayer Healthcare Ag | Nouvelle utilisation d'antibiotiques du groupe quinolone |
WO2007101560A1 (fr) * | 2006-03-08 | 2007-09-13 | Bayer Animal Health Gmbh | Formulations de médicaments contenant des fluoroquinolones |
WO2008025380A1 (fr) * | 2006-03-08 | 2008-03-06 | Bayer Animal Health Gmbh | Médicament contenant de la fluoroquinolone |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005018641A2 (fr) * | 2003-08-13 | 2005-03-03 | Bayer Healthcare Ag | Nouvelle utilisation d'antibiotiques du groupe quinolone |
WO2007101560A1 (fr) * | 2006-03-08 | 2007-09-13 | Bayer Animal Health Gmbh | Formulations de médicaments contenant des fluoroquinolones |
WO2008025380A1 (fr) * | 2006-03-08 | 2008-03-06 | Bayer Animal Health Gmbh | Médicament contenant de la fluoroquinolone |
Non-Patent Citations (1)
Title |
---|
RECABARREN M P ET AL: "Differential effects of infralimbic cortical lesions on temperature and locomotor activity responses to feeding in rats", NEUROSCIENCE, NEW YORK, NY, US, vol. 134, no. 4, 1 January 2005 (2005-01-01), pages 1413 - 1422, XP025367126, ISSN: 0306-4522, [retrieved on 20050101] * |
Cited By (2)
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GB2480276A (en) * | 2010-05-11 | 2011-11-16 | Michael Hilary Burke | Process for the preparation of an aqueous injectable enrofloxacin antimicrobial formulation |
CN110327348A (zh) * | 2019-07-19 | 2019-10-15 | 余祖功 | 含恩诺沙星和美洛昔康的复方长效注射液及其制备方法 |
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