IE51846B1 - Pharmaceutical preparation for veterinary use and an appliance containing it - Google Patents
Pharmaceutical preparation for veterinary use and an appliance containing itInfo
- Publication number
- IE51846B1 IE51846B1 IE2572/81A IE257281A IE51846B1 IE 51846 B1 IE51846 B1 IE 51846B1 IE 2572/81 A IE2572/81 A IE 2572/81A IE 257281 A IE257281 A IE 257281A IE 51846 B1 IE51846 B1 IE 51846B1
- Authority
- IE
- Ireland
- Prior art keywords
- preparation according
- salt
- preparation
- treatment
- acid
- Prior art date
Links
- 239000000825 pharmaceutical preparation Substances 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- 229940002612 prodrug Drugs 0.000 claims abstract description 11
- 239000000651 prodrug Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims abstract description 9
- 239000002132 β-lactam antibiotic Substances 0.000 claims abstract description 9
- 229940124586 β-lactam antibiotics Drugs 0.000 claims abstract description 9
- 150000002148 esters Chemical class 0.000 claims abstract description 7
- 238000001727 in vivo Methods 0.000 claims abstract description 4
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 3
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 3
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 3
- 208000031462 Bovine Mastitis Diseases 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 29
- 239000000725 suspension Substances 0.000 claims description 19
- 208000004396 mastitis Diseases 0.000 claims description 13
- AFKRZUUZFWTBCC-WSTZPKSXSA-N 2-(diethylamino)ethyl (2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical class N([C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)OCCN(CC)CC)C(=O)CC1=CC=CC=C1 AFKRZUUZFWTBCC-WSTZPKSXSA-N 0.000 claims description 8
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- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- ZEMIJUDPLILVNQ-ZXFNITATSA-N pivampicillin Chemical class C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 ZEMIJUDPLILVNQ-ZXFNITATSA-N 0.000 claims description 8
- XWRCFDRXQPRCCO-FLQNVMKHSA-N 2-[(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carbonyl]oxyethyl-diethylazanium;iodide Chemical compound I.N([C@H]1[C@@H]2N(C1=O)[C@H](C(S2)(C)C)C(=O)OCCN(CC)CC)C(=O)CC1=CC=CC=C1 XWRCFDRXQPRCCO-FLQNVMKHSA-N 0.000 claims description 6
- -1 alkali metal salt Chemical class 0.000 claims description 6
- PFOLLRNADZZWEX-FFGRCDKISA-N bacampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OC(C)OC(=O)OCC)=CC=CC=C1 PFOLLRNADZZWEX-FFGRCDKISA-N 0.000 claims description 5
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- 241001465754 Metazoa Species 0.000 description 2
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 2
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- KLOHDWPABZXLGI-YWUHCJSESA-M ampicillin sodium Chemical compound [Na+].C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 KLOHDWPABZXLGI-YWUHCJSESA-M 0.000 description 2
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- ACTOXUHEUCPTEW-BWHGAVFKSA-N 2-[(4r,5s,6s,7r,9r,10r,11e,13e,16r)-6-[(2s,3r,4r,5s,6r)-5-[(2s,4r,5s,6s)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2s,5s,6r)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-o Chemical compound O([C@H]1/C=C/C=C/C[C@@H](C)OC(=O)C[C@@H](O)[C@@H]([C@H]([C@@H](CC=O)C[C@H]1C)O[C@H]1[C@@H]([C@H]([C@H](O[C@@H]2O[C@@H](C)[C@H](O)[C@](C)(O)C2)[C@@H](C)O1)N(C)C)O)OC)[C@@H]1CC[C@H](N(C)C)[C@@H](C)O1 ACTOXUHEUCPTEW-BWHGAVFKSA-N 0.000 description 1
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- 229960003276 erythromycin Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229960003704 framycetin Drugs 0.000 description 1
- PGBHMTALBVVCIT-VCIWKGPPSA-N framycetin Chemical compound N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CN)O2)N)O[C@@H]1CO PGBHMTALBVVCIT-VCIWKGPPSA-N 0.000 description 1
- 229960004675 fusidic acid Drugs 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000010512 hydrogenated peanut oil Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960003085 meticillin Drugs 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
- GPXLMGHLHQJAGZ-JTDSTZFVSA-N nafcillin Chemical compound C1=CC=CC2=C(C(=O)N[C@@H]3C(N4[C@H](C(C)(C)S[C@@H]43)C(O)=O)=O)C(OCC)=CC=C21 GPXLMGHLHQJAGZ-JTDSTZFVSA-N 0.000 description 1
- 229960000515 nafcillin Drugs 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229960002950 novobiocin Drugs 0.000 description 1
- YJQPYGGHQPGBLI-KGSXXDOSSA-N novobiocin Chemical compound O1C(C)(C)[C@H](OC)[C@@H](OC(N)=O)[C@@H](O)[C@@H]1OC1=CC=C(C(O)=C(NC(=O)C=2C=C(CC=C(C)C)C(O)=CC=2)C(=O)O2)C2=C1C YJQPYGGHQPGBLI-KGSXXDOSSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 1
- 229960001019 oxacillin Drugs 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000024 polymyxin B Polymers 0.000 description 1
- 229960005266 polymyxin b Drugs 0.000 description 1
- 229940041153 polymyxins Drugs 0.000 description 1
- 229960005009 rolitetracycline Drugs 0.000 description 1
- HMEYVGGHISAPJR-IAHYZSEUSA-N rolitetracycline Chemical compound O=C([C@@]1(O)C(O)=C2[C@@H]([C@](C3=CC=CC(O)=C3C2=O)(C)O)C[C@H]1[C@@H](C=1O)N(C)C)C=1C(=O)NCN1CCCC1 HMEYVGGHISAPJR-IAHYZSEUSA-N 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229960000268 spectinomycin Drugs 0.000 description 1
- UNFWWIHTNXNPBV-WXKVUWSESA-N spectinomycin Chemical compound O([C@@H]1[C@@H](NC)[C@@H](O)[C@H]([C@@H]([C@H]1O1)O)NC)[C@]2(O)[C@H]1O[C@H](C)CC2=O UNFWWIHTNXNPBV-WXKVUWSESA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000019372 spiramycin Nutrition 0.000 description 1
- 229960001294 spiramycin Drugs 0.000 description 1
- 229930191512 spiramycin Natural products 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004306 sulfadiazine Drugs 0.000 description 1
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 1
- JNMRHUJNCSQMMB-UHFFFAOYSA-N sulfathiazole Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CS1 JNMRHUJNCSQMMB-UHFFFAOYSA-N 0.000 description 1
- 229960001544 sulfathiazole Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- UURAUHCOJAIIRQ-QGLSALSOSA-N tiamulin Chemical compound CCN(CC)CCSCC(=O)O[C@@H]1C[C@@](C)(C=C)[C@@H](O)[C@H](C)[C@@]23CC[C@@H](C)[C@]1(C)[C@@H]2C(=O)CC3 UURAUHCOJAIIRQ-QGLSALSOSA-N 0.000 description 1
- 229960004885 tiamulin Drugs 0.000 description 1
- 229960004659 ticarcillin Drugs 0.000 description 1
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 229960004059 tylosin Drugs 0.000 description 1
- 235000019375 tylosin Nutrition 0.000 description 1
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0041—Mammary glands, e.g. breasts, udder; Intramammary administration
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Pharmaceutical preparations for veterinary use comprise a 6 beta - halopenicillanic acid as such or a salt thereof or an ester thereof which is hydrolyzable in vivo or a salt of such an ester together with one or more beta - lactam antibiotics (e.g. specified penicillins or cephalosporins), as such or in the form of their pro-drugs, and together with a pharmaceutically acceptable, non-toxic carrier and/or auxiliary agent. The preparation may contain other active ingredients and is preferably compounded with an oleaginous carrier. The preparation is suitable for intramammary use for the treatment of bovine mastitis and for similar local treatment of cavities.
Description
The present invention relates to a pharmaceutical preparation for veterinary use. More particularly, it relates to a pharmaceutical preparation for the treatment of bacterial infections in animals. In particular, the present invention relates to a pharmaceutical preparation especially well suited for intramammary use and similar local treatment of cavities, and an appliance containing such preparation.
Pharmaceutical preparations for intramammary use are particularly intended for the treatment of mastitis. Great efforts and high costs have during the years been invested in developing products for the treatment of mastitis, an inflammation of the udder caused by a bacterial infection, this disease being of importance for dairy production.
It has now been found that a 6B-halopenicillanic acid administered as a salt or an in vivo hydrolyzable ester penetrates the udder tissue causing in milk and/or serum a high concentration of the 6B-halopenicillanic acid which in turn causes a protection of a β-lactam antibiotic used in the treatment of an infection and/or enhances the effect of the antibiotic in question.
According to the present invention there is provided a pharmaceutical veterinary preparation in dosage unit form for intramammary use and similar local treatment of cavities, comprising (a) a 6B-halopenicillanic acid as such or in the form of a salt or an in vivo hydrolyzable ester or a salt of such ester as a first active ingredient, (b) one or more β-lactam antibiotics as such or in the form of a pro-drug as a second and different active ingredient, (c) optionally a further active ingredient, and (d) one or more pharmaceutically acceptable, non-toxic carriers and/or auxiliary agents presenting the preparation as a solution or suspension in a non-aqueous medium, the dosage unit containing from 0.025 g. to 2,5 g. of the active ingredients the total amount of which is from 0.5 to 40 w/v per cent.
The invention also provides an appliance for intramammary use containing a dosage unit of the pharmaceutical veterinary preparation just described. The appliance is conveniently an intramammary injector or an aerosol dispenser.
Such preparations may also contain a salt of a όβ-halopenicillanic acid with a β-lactara antibiotic or a pro-drug thereof having a basic group. Among suitable β-lactam antibiotics for such preparations can be mentioned: penicillin G andV, ampicillin, amoxycillin, epicillin, carbenicillin, cloxacillin, azlocillin, flucloxacillin, ticarcdllin, nafcillin, dicloxacillin, oxacillin, methicillin, carfecillin, mecillinam, cephalothin, cephaloridine, cephaloglycin, cephazolin, cephacetrile, cefoxitin, cephalexin, cephoxazole cephalonium, or pro-drugs thereof, and mixtures of one or more of such β-lactam antibiotics or pro-drugs thereof, for example: ampicillin/cloxaoillin, amoxycillin/cloxacillin ampicillin/flucloxacillin, amoxycillin/flucloxacillin, ticar cillin/flucloxacillin and ampicillin/mecillinam, or similar combinations containing pro-drugs, without this enumeration being considered as limiting.
A pharmaceutical preparation which is specifically of importance contains as the antibiotic part benzylpenicillin in the form of its β-diethylaminoethyl ester having the generic name penethamate.
Penethamate as such or e.g. in the form of its hydroiodide is known to be very effective in the treatment of mastitis by giving rise to a rapid and high concentration of benzylpenicillin in the udder.
Also aminopenicillins, e.g. ampicillin, amoxycillin or pro-drugs thereof, are highly effective in the treatment of mastitis.
As is well known, certain penicillins, e.g, penicillin G and V and aminopenicilline, are very sensitive to β-lactamases and consequently the combination of these antibiotics (or their pro-drugs) with a 6p~halopenicillanie acid in an anti-mastitis preparation is appi'opriate due to its protection of the penicillin. In such preparations other β-lactam antibiotics, e.g, those mentioned above, have been included in order to obtain a broader antibacterial spectrum and/or an enhancement of the antibacterial activity and/or a synergistic effect. In a particular embodiment a salt of a όβ-halopenicillanic acid with penethamate, pivampicillin or bacampicillin can be used in the combination.
Other antibiotics which can be present in the antimastitis preparation according to the invention are by way of example! tetracyclines, e.g. tetracycline, oxytetracycline, chlortetracycline and rolitetracycline; sulphonamides, e.g. sulphadiazine, sulphadoxine, sulphatroxazole, sulphadimidine and sulphathiazole; trimethoprim; aminoglycoside aminocyclitols, e.g. streptomycin, dihydrostreptomycin, kanamycin, gentamycin, neomycin, framycetin and apranycin; aminocyclitols, e.g. spectinomycin; chloramphenicol;fusidic acid; linconiycin; macrolides, e.g. erythromycin, tylosin, spiramycin and oleandcnycin; novobiocin; polymyxins, e.g. polymyxin B and E; and pleuromutilins, e.g. tiamulin, this enumeration not to be considered as limiting the present invention.
Appropriately, and in accordance with common practice, the anti-mastitis preparation can also contain, for example, a corticosteroid or pain-relieving agents or other similar acting components.
The composition of the invention for use in the treatment ul' m.-i s I. i I. i s comprises suspensions or solutions of the active components in a suitable vehicle which can be an oily base.
The composition can be administered in conventional ways for the treatment of mastitis, e.g. with an intramammary injector or in the form of an aerosol. In the preferred embodi ment the composition can be administered as an aerosol foam.
With a view to obtaining the highest degree of stability the vehicle is a non-aqueous medium such as a vegetable oil or paraffin oil. Appropriately a thickening agent can be added such as 12-hydroxystearin or aluminium stearate. Also as thickening agents there can be used beeswax, hydrogenated peanut or castor oil or soft or hard paraffin.
Furthermore, as a thickener use can be made of e.g. lactose.
Further, the composition used in the treatment of mastitis can appropriately contain surfactants such as Span, IWeen, or Cremqphor (Span, TV/een and Cremophor are Trade Marks).
Conventionally such additives are used in amounts up to 10 w/v per cent of the composition, whereas the amount of detergent appropriately varies between 0.1 and 8 w/v per cent.
The vegetable oil can advantageously be chosen from among commercially available oils, the fatty acids of which contain from 8 to 10 carbon atoms. Particularly useful are commercial products with low viscosity, such as Viscoleo. which is fractionated coconut oil.
The amount of the therapeutically active agents in total in the anti-mastitis preparations above can appropriately vary from 0.5 to 40 w/v per cent.
The dosage unit of the preparation is selected to be one 5 which can be administered so that the desired results are achieved without simultaneous secondary effects.
The dosage unit preferably contains from 0.1 g to 1 g of the active ingredients, e.g. the β-lactam antibiotic (s) and the β-lactamase inhibitor.
In the treatment of mastitis the composition or com10 pounded composition of the invention is appropriately administered by an injector (intramammary) containing e.g. 5 ml.
The present invention also comprises a method for the treatment of non-human animals, consisting in the administration of an effective amount of the present compositions to the animal suffering from an infectious disease.
In the lactation period in which a short period of treatment is desirable, the composition is appropriately given in a dose amounting to 5-1θ ml per quarter of a composition With a base consisting mostly of vegetable oils in order to obtain rapid excretion of the active ingredients.
In the dry period the composition or compounded composition can appropriately be based upon paraffin or vegetable oils with aluminium stearate and preferably containing other antimicrobial agents, e.g. streptomycin.
The method may consist in administering compositions or compounded compositions of the invention, or in admini5 stering such compositions together with compositions containing other antibiotics. In the latter case, the two types of compositions may be administered simultaneously or at intervals and with varying proportions between the active components in the compositions.
In the treatment of mastitis the infected quarter is treated with contents of the intramammaiy injector every 12 or 24 hours in the lactation period until the infection ceases normally after 3 treatments, and in the dry period the infected quarter is appropriately treated with one or more single long-term doses, depending upon the length of the dry period.
The invention will be further described in the follow ing Examples which are not to be construed as limiting the invention.
Example 1 The following composition is prepared: Penethamate hydriodide 100 g Potassium 6p-bromopenicillanate 100 g 12-Hydroxystearin, known under the trade name of Thixcin R 20 g . Modified coconut oil, known under the trade names of Miglyol 812 R and Neobee R 780 g 1000 g The 12-hydroxystearin is dissolved in the coconut oil at 70°C and cooled to room temperature. Penethamate hydroiodide and potassium 6p-bromopenicillanate are incorporated therein by agitation followed by homogenization. The resulting suspension is filled into plastic syringes, each containing 5 S °f the suspension.
Example 2 The following composition is prepared in accordance with the procedures set forth in Example 1.
Penethamate hydriodide 100 g Potassium 6p-iodopenicillanate 50 g Polysorbate 80 10 g 12-Hydroxystearin 25 g Modified coconut oil 815 ε 1000 g 5184 6 The resulting suspension was then filled into plastic syringes, each containing 5 S of the suspension.
Example 3 The following composition is prepared: Penethamate hydriodide 20 g Potassium δβ-bromopenicillanate UO g Framycetin sulfate 20 g Aluminium monostearate 20 g 12-Hydroxystearin 10 g Liquid paraffin 890 g 1000 g The aluminium monostearate and the 12-hydroxystearin are dissolved in the liquid paraffin at 130°C and cooled to 30°C. The penethamate hydriodide, potassium 6p-iodopeni15 cillanate and framycetin sulfate are incorporated therein by agitation followed by homogenization. The resulting suspension is filled into plastic syringes, each containing 5 g of the suspension.
Example 4 The procedures of Example 1 were repeated to prepare a similar composition except that the penethamate hydriodide was replaced by an equivalent amount of the penethamate salt of 6p-bromopenicillanic acid. 195 syringes of the resulting suspension were prepared.
Example 5 The following composition is prepared! Ampicillin 3θ g Potassium 6p-broroopenicillanate 3θ g 12-Hydroxystearin 20 g Polysorbate 80 20 g Coconut oil modified 900 K 1000 g 12-Hydroxystearin and polysorbate 80 are dissolved in 10 coconut oil at 80°C and cooled to room temperature. Ampicillin and potassium 6p-bromopenicillanate are incorporated by agitation followed by homogenization. The suspension is filled into plastic syringes each containing 5 g of the suspension.
Example 6 The following composition is prepared! Sodium ampicillin 40 g Sodium 6p-bromopenicillanate 20 g Siliciumdioxide JO g Stearyl alcohol 20 g 20 Peanut oil 890 g 1000 g Stearylalcohol is dissolved in peanut oil at 6j°C and cooled to.room temperature. Silicium dioxide, sodium ampicillin and sodium 6p-bromopenicillanate are incorporated by agitation followed by homogenization. The suspension is filled into plastic syringes each containing 5 S bhe suspension.
Example 7 The following composition is prepared; Pivampicillin 100 g Sodium 6p-bromopenicillanate 50 g 12-Hydroxystearin 25 g Coconut oil modified 825 g 1000 g 12-Hydroxystearin is dissolved in coconut oil at 80°C and cooled to room temperature. Pivampicillin and sodium 6p-bromopenicillanate are incorporated by agitation followed by homogenization. The suspension is filled into plastic syringes each contai ning 5 g of the suspension.
Example 8 The following composition is prepared: Bacampieillin 40 g Potassium 6p-bromopenicillanate 10 g Aluminiummonostearate 20 g 12-Hydroxystearin 20 g Liquid paraffin 910 g 1000 g Aluminiummonostearate and 12-hydroxystearin are dissolved in liquid paraffin at 130°C and cooled to 30°C, Pivampicillin and potassium 6p-bromopenici1lanate are incorporated by agitation followed by homogenization. The suspension is filled into plastic syringes each containing 5 g of the suspension.
Example 9-13 The procedures of Example 1 were repeated to prepare a similar composition, except that the penethamate hydro10 iodide was replaced by an equivalent amount of the penethamate salt of όβ-iodopenicillanic acid, the bacampicillin salt of 6p-bromopenicillanic acid, the bacampicillin salt of 6p-iodopenicillanic acid, the pivampicillin salt of 6p-bromopenicillanic acid, or the pivampicillin salt of 6p-iodopenicillanic acid, respectively.
Claims (17)
1. CLAIMS:1. A pharmaceutical veterinary preparation in dosage unit form for intramammary use and similar local treatment of cavities, comprising, 5 (a) a 6p-halopenicillanic acid as such or in the form of a salt or an in vivo hydrolyzable ester or a salt of such ester as a first active ingredient, (b) one or more β-lactam antibiotics as such or in the form of a pro-drug as a second and different active 10 ingredient, (c) optionally a further active ingredient, and (d) one or more pharmaceutically acceptable, non-toxic carriers and/or auxiliary agents presenting the preparation as a solution or suspension in a non-aqueous medium, the 15 dosage unit containing from 0.025 g. to 2.5 g. of the active ingredients the total amount of which is from 0.5 to 40 w/v per cent.
2. A preparation according to claim 1, wherein the dosage unit contains from 0.1 to 1.0 g. of the active ingredients. 20
3. A preparation according to claim 1 or 2, containing an alkali metal salt of a 6f3-halopenicillanic acid.
4. A preparation according to claim 1, containing penethamate hydriodide.
5. A preparation according to claim 1 or 2, containing a salt of a 66-halopenicillanic acid with a β-lactam antibiotic or a pro-drug thereof containing a basic group.
6. A preparation according to claim 5, containing the penethamate salt of 68-bromopenicillanic acid or 6fi-iodopenicillanic acid.
7. A preparation according to claim 5, containing the bacampicillin or pivampicillin salt of 68-bromo- or δβ-iodopenicillanic acid.
8. A preparation according to claim 1, containing ampicillin as such or as an alkali metal salt or as a pro-drug.
9. A preparation according to claim 1, containing pivampicillin or bacampicillin.
10. A preparation according to any one of claims 1 to 9 in the form of a solution or a suspension of the active ingredients in a non-aqueous medium and contained in an intramammary injector.
11. A pharmaceutical veterinary preparation for intramammary use and similar local treatment of cavities substantially as hereinbefore described in any one of the foregoing Examples.
12. An appliance for intramammary use containing a dosage unit of the pharmaceutical veterinary preparation according to any preceding claim.
13. An appliance as claimed in claim 12 in the form of an intramammary injector,
14. An appliance as claimed in claim 12 in the form of an aerosol dispenser. 5 15. A method for the treatment of infectious diseases caused by bacteria, in particular mastitis, in non-human animals, which comprises administering a preparation according to any one of claims 1 to 10 alone or together with preparations containing other antibiotics, such 10 combined administration being undertaken simultaneously or at intervals, and optionally with varying proportions between the active components in the compositions. 16. A method according to claim 15 for the treatment of mastitis in the lactation period, in which the infected
15. Quarter is treated every 12 or 24 hours in the bovine lactation period with a preparation according to claim 10, until the infection ceases.
16. 17. A method according to claim 15 for the treatment of bovine mastitis in the dry period, in which the infected
17. 20 quarter is treated with one or more single long-term doses
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/207,614 US4446144A (en) | 1979-05-21 | 1980-11-17 | Derivatives of penicillanic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE812572L IE812572L (en) | 1982-05-17 |
| IE51846B1 true IE51846B1 (en) | 1987-04-15 |
Family
ID=22771286
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2572/81A IE51846B1 (en) | 1980-11-17 | 1981-11-03 | Pharmaceutical preparation for veterinary use and an appliance containing it |
Country Status (8)
| Country | Link |
|---|---|
| AU (1) | AU553440B2 (en) |
| DE (1) | DE3145488A1 (en) |
| FR (1) | FR2494115A1 (en) |
| GB (1) | GB2087236B (en) |
| IE (1) | IE51846B1 (en) |
| NL (1) | NL8105212A (en) |
| NZ (1) | NZ198878A (en) |
| ZA (1) | ZA817679B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8405611D0 (en) * | 1984-11-09 | 1984-11-09 | Astra Laekemedel Ab | PROCESS FOR STABILIZATION OF BACAMPICILLIN HYDROCHLORIDE |
| JPS6219592A (en) * | 1985-07-17 | 1987-01-28 | Yoshitomi Pharmaceut Ind Ltd | Production of bacampicillin-6beta-halopenicillanate |
| WO2003063877A1 (en) * | 2002-02-01 | 2003-08-07 | Akzo Nobel N.V. | Cefquinome composition for intra-mammary administration in cattle |
| AU2003269311A1 (en) * | 2002-10-08 | 2004-05-04 | Ancare New Zealand Ltd. | Antibiotic formulation for intramammary administration in milking animals |
| DE60305728T2 (en) * | 2002-10-25 | 2006-10-12 | Intervet International Bv | Extended release pharmaceutical composition |
| US6911441B2 (en) | 2002-12-16 | 2005-06-28 | Akzo Nobel N.V. | Prolonged release pharmaceutical composition |
| EP1568369A1 (en) | 2004-02-23 | 2005-08-31 | Boehringer Ingelheim Vetmedica Gmbh | Use of meloxicam for the treatment of respiratory diseases in pigs |
| DE102004025324A1 (en) * | 2004-05-19 | 2005-12-08 | Boehringer Ingelheim Vetmedica Gmbh | Liquid preparation for veterinary medicine, process for their preparation and their use |
| EP2874623B1 (en) * | 2012-07-17 | 2018-12-12 | Bayer New Zealand Limited | Injectable antibiotic formulations and their methods of use |
| TWI631948B (en) * | 2012-07-17 | 2018-08-11 | 拜爾紐西蘭有限公司 | Injectable antibiotic formulations and their methods of use |
| CN104470517B (en) * | 2012-07-17 | 2018-12-18 | 拜耳新西兰有限公司 | Injection antibiotic formulations and its application method |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4180506A (en) * | 1978-01-18 | 1979-12-25 | Rex Pratt | 6β-Bromo penicillanic acid |
| EP0013617B1 (en) * | 1979-01-10 | 1984-07-04 | Beecham Group Plc | Penicillin derivatives, process for their preparation and pharmaceutical compositions containing certain of these compounds |
| US4397783A (en) * | 1979-03-05 | 1983-08-09 | Pfizer Inc. | Process for converting 6,6-disubstituted penicillanic acid derivatives to the 6-β-congeners |
| IL59948A0 (en) * | 1979-05-21 | 1980-06-30 | Rech Applications Therap | Penicillanic acid derivatives,their production and pharmaceutical compositions containing them |
-
1981
- 1981-11-03 IE IE2572/81A patent/IE51846B1/en not_active IP Right Cessation
- 1981-11-05 NZ NZ198878A patent/NZ198878A/en unknown
- 1981-11-06 ZA ZA817679A patent/ZA817679B/en unknown
- 1981-11-11 AU AU77392/81A patent/AU553440B2/en not_active Ceased
- 1981-11-16 DE DE19813145488 patent/DE3145488A1/en not_active Withdrawn
- 1981-11-16 FR FR8121386A patent/FR2494115A1/en active Granted
- 1981-11-16 GB GB8134476A patent/GB2087236B/en not_active Expired
- 1981-11-17 NL NL8105212A patent/NL8105212A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB2087236B (en) | 1984-08-01 |
| FR2494115B1 (en) | 1985-01-25 |
| FR2494115A1 (en) | 1982-05-21 |
| ZA817679B (en) | 1982-10-27 |
| DE3145488A1 (en) | 1982-06-24 |
| AU7739281A (en) | 1982-05-27 |
| GB2087236A (en) | 1982-05-26 |
| NZ198878A (en) | 1986-07-11 |
| NL8105212A (en) | 1982-06-16 |
| AU553440B2 (en) | 1986-07-17 |
| IE812572L (en) | 1982-05-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |